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Enrollment Trends and Disparity Among Patients With Lung Cancer in National Clinical Trials, 1990 to 2012
Abstract
Purpose:
Under-representation of elderly, women, and racial/ethnic minority patients with cancer in clinical trials is of national concern. The goal of this study was to characterize enrollment trends and disparities by age, sex, and race/ethnicity in lung cancer trials.
Methods:
We analyzed data for 23,006 National Cancer Institute cooperative group lung cancer trial participants and 578,476 patients with lung cancer from the SEER registry from 1990 to 2012. The enrollment disparity difference (EDD) and enrollment disparity ratio (EDR) were calculated on the basis of the proportion of each subgroup in the trial population and the US lung cancer population. Annual percentage changes (APCs) in the subgroup proportions in each population were compared over time.
Results:
Enrollment disparity for patients ? 70 years of age with non-small-cell lung cancer improved from 1990 to 2012 (test of parallelism, P = .020), with a remaining EDD of 0.22 (95% CI, 0.19 to 0.25) and EDR of 1.65 (95% CI, 1.51 to 1.82) in 2010 to 2012. No improvement was seen for elderly patients with small-cell lung cancer (SCLC), with an APC of 0.20 (P = .714) among trial participants, despite a rising proportion of elderly patients with SCLC in the US population (APC, 0.32; P = .020). Enrollment disparity for women with lung cancer improved overall, with the gap closing by 2012 (EDD, 0.03 [95% CI, 0.00 to 0.06]; EDR, 1.07 [95% CI, 1.00 to 1.16]). Enrollment disparities persisted without significant improvement for elderly women, blacks, Asians/Pacific Islanders, and Hispanics.
Conclusion:
Under-representation in lung cancer trials improved significantly from 1990 to 2012 for elderly patients with non-small-cell lung cancer and for women, but ongoing efforts to improve the enrollment of elderly patients with SCLC and minorities are needed. Our study highlights the importance of addressing enrollment disparities by demographic and disease subgroups to better target under-represented groups of patients with lung cancer.
... Factors influencing LDCT screening rates in the general population include limited access to screening tests and smoking cessation programs, limited patient acceptance, and inconsistent provider knowledge about screening guidelines [20,21]. In addition, Black smokers are more likely to be unaware of the availability of lung cancer screening, be under-insured, and have lower socioeconomic status, all of which contribute to suboptimal screening rates for lung cancer [22][23][24][25]. In addition, structural barrierspoverty, transportation, racism and interpersonal barriersfear and medical mistrust, further influence lung cancer screening disparities among Black smokers [26,27]. ...
... (P. 24) "They told me I should take the patch. Put the patch on every day." ...
... (P. 24) "Chest pains. Breathing problems. ...
... Epidemiological studies have reported that > 50% of patients with lung cancer are ≥ 65 years old, the threshold often used to define the "elderly" population in such studies (Davidoff et al. 2010). Despite this, patients aged ≥ 75 years are underestimated in clinical trials, with < 10% of those in the National Cancer Institute collaborative group studies having non-small-cell lung cancer (NSCLC) (Sacher et al. 2013;Pang et al. 2016). ...
Purpose
Nivolumab plus ipilimumab (Nivo-Ipi) combination therapy is an effective first-line treatment for advanced non-small cell lung cancer (NSCLC). However, its effectiveness and feasibility in elderly patients (aged ≥ 75 years) remain unclear. This study aimed to investigate the efficacy and safety of first-line Nivo-Ipi therapy in elderly patients with NSCLC.
Methods
This retrospective study included 57 patients with NSCLC (52 men and 5 women), aged ≥ 75 years (range: 75–86) who received first-line Nivo-Ipi therapy from December 2020 to November 2022 at four institutes in Japan. Patient characteristics, therapeutic efficacy, and the incidence and severity of adverse events (AE) were assessed.
Results
The overall response rate was 42.1%, the disease control rate was 73.6%, the median progression-free survival (PFS) was 7.1 months, and the median overall survival (OS) was 14.1 months. Common Grade ≥ 3 AEs included pneumonitis, elevated aspartate transaminase, elevated alanine transaminase, adrenal insufficiency, and colitis. No treatment-related deaths were reported. PFS and OS were longer in patients who experienced treatment-related AEs. Patients with and without AEs had a median PFS of 11.7 and 2.8 months, respectively. Similarly, the median OS of patients with and without AEs was 20.4 and 9.0 months, respectively.
Conclusion
First-line Nivo-Ipi therapy is effective in elderly patients with NSCLC. Although there was an increased incidence of pneumonitis, the treatment was manageable and presented as a viable treatment option. Notably, the occurrence of treatment-related AEs was associated with improved clinical outcomes, suggesting a potential prognostic value of AEs in this population.
... Previous studies have also noted improvements in sex equity in clinical trial participation in recent years. 29,30 However, achieving sex parity in enrollment does not necessarily mean that trials are designed to examine sexspecific outcomes or differences in treatment efficacy and side effects. For example, evidence suggests that men and women may experience different side effects or responses to certain antiseizure medications due to hormonal differences, metabolism, or other biological factors. ...
Objective
Studies have shown that a growing number of people with epilepsy belong to minority groups and experience health disparities. Inclusivity in clinical trial enrollment is essential for advancing health access but has not been well studied among epilepsy trials. The objective of this study was to analyze US epilepsy clinical trials to identify the prevalence and trends associated with race and sex enrollment disparities.
Methods
We queried the Clinicaltrials.gov registry to identify completed epilepsy clinical trials with results reported between 2006 and 2022. Studies were assessed for reporting of participant race and sex information, and measures of trial diversity including the participation to prevalence ratio (PPR), representation ratio (RR), and representation quotient (RQ) were calculated. Other data including funding source, intervention type, location, and trial dates were also extracted.
Results
Ninety trials met inclusion criteria, of which 89 (99%) and 53 (59%) reported participant sex and race, respectively. Three trials included only female participants and were excluded from further sex‐specific analyses. Females were underrepresented in 10 of the remaining 86 trials reporting sex information (PPR < .8, 12%). We found that industry‐funded trials were more likely to have equal female representation among participants (p = .0197). Of trials reporting participant race, 52 (98%) exhibited a lack of racial diversity (RQ < 1). Black participants were the most frequently underrepresented racial group (RR < 1, 42 of 53 trials, 79%).
Significance
Our findings highlight significant disparities in epilepsy clinical trial enrollment, particularly for Black participants. Lack of diversity and underrepresentation of historically marginalized populations may contribute to research biases and perpetuate health inequities. More inclusive research practices are needed to ensure all people with epilepsy have access to effective care.
... To examine the temporal trend in EIR between 2007 and 2022, the average annual percentage change (AAPC) in the EIR was calculated using the Joinpoint Regression Program. 17 All other analyses were performed using R programming language (version 4.2.0; R Foundation for Statistical Computing, Vienna, Austria). ...
PURPOSE
Minoritized racial/ethnic groups are historically under-represented in cancer clinical trials, which may be exacerbated in recent trials on immune checkpoint inhibitors (ICIs). We examined the representation and reporting of the racial/ethnic composition of participants in clinical trials on ICIs.
METHODS
We examined English full-text trials on ICIs published from 2007 to 2022. Information on trial characteristics and racial/ethnic composition of participants was extracted from published papers or ClinicalTrials.gov. Differences in participation by publication year, ICI agent, and cancer site were analyzed. Enrollment-incidence ratio (EIR) was calculated to compare the proportion of minoritized racial/ethnic group patients in US-based trials against age-adjusted cancer incidence data available for the US population. An EIR > 1 signified over-representation, whereas an EIR <1 signified under-representation.
RESULTS
Of the 471 trials examined, racial composition was unreported in 146 (31%), whereas Hispanic/Latinx ethnicity was unreported in 278 (59%). Only 30 (6%) trials reported race/ethnicity-specific results. In US-only trials (n = 174), White patients were over-represented (EIR, 1.20 [95% CI, 1.17 to 1.22]), whereas Hispanic/Latinx patients were the most under-represented (EIR, 0.35 [95% CI, 0.24 to 0.48]), followed by Black/African American patients (EIR, 0.66 [95% CI, 0.54 to 0.79]). Subgroup analyses consistently indicated over-representation of White patients across publication years (EIR, 1.19-1.24), ICI classes (EIR, 1.16-1.23), and cancer sites (EIR, 1.11-1.31), whereas Hispanic/Latinx patients were consistently under-represented. An upward trend of trial representation and reporting was observed for all minoritized racial/ethnic groups over time (trend P values ≤.05).
CONCLUSION
Disparities in the representation and reporting of minoritized racial/ethnic groups persist in recent trials on ICIs, necessitating collaborative efforts for improved diversity and equitable cancer treatment access.
... We hypothesize that older patients with NSCLC and SBM treated with subsequent ICI therapy exhibit improved OS compared to those treated with subsequent chemotherapy. Patients 65 years or older account for approximately 71% of patients with lung cancer (25), but are underrepresented in clinical studies due to advanced age, poor PS, lack of social support, or multiple comorbid conditions (26,27). Thus, there exists an urgent need to understand the treatment outcomes of ICIs in this patient population. ...
Background:
Immune checkpoint inhibitors (ICIs) have become the mainstay treatment for non-small cell lung cancer (NSCLC). However, there is a lack of studies assessing ICIs as subsequent treatment in older adults with NSCLC and brain metastasis (BM). This retrospective cohort study compared the real-world survival of older patients with NSCLC and BM at diagnosis [synchronous BM (SBM)] previously treated with chemotherapy receiving ICI versus chemotherapy as subsequent treatment.
Methods:
Patients with NSCLC and SBM ≥65 years previously treated with chemotherapy were identified using the SEER-Medicare database (2010-2019). Patients receiving new chemotherapy and/or Food and Drug Administration (FDA)-approved ICIs as second/third-line treatment were included, excluding those ever-receiving targeted therapies. Each ICI patient was matched to one chemotherapy patient by time to subsequent treatment (within ±30 days) from diagnosis. Overall survival (OS) time was measured from the start of subsequent treatment to death, censored at disenrollment from Medicare Part A/B, enrollment in Part C, or end of study (December 31, 2019), whichever came first. OS curves were estimated and compared using the Kaplan-Meier (KM) method and log-rank test. Hazard ratio (HR) was estimated using a multivariable-adjusted Cox proportional hazards model.
Results:
Matched cohorts included 546 patients [273 in each group; median age 71 (range, 65-87) years]. ICI patients were older, more likely non-Hispanic, with squamous cell carcinoma, and liver metastasis compared to chemotherapy. KM estimated better survival in ICI than chemotherapy {median survival: 209 days [95% confidence interval (CI): 160-275] vs. 155 days (95% CI: 135-187); log-rank P<0.001}. ICI was associated with a lower adjusted hazard of death [HR =0.63; 95% CI: 0.52-0.75; P<0.001] compared to subsequent chemotherapy treatment.
Conclusions:
In this population-based study of older patients with NSCLC and SBM previously treated with chemotherapy, subsequent treatment with ICI was associated with improved survival compared to chemotherapy.
... Although the incidence and prevalence of cancer are increasing among patients ! 75 years old, <10% of patients enrolled in the National Cancer Institute collaborative group studies have non-small-cell lung cancer (NSCLC); this subpopulation is therefore often underestimated in clinical studies (4,5). ...
Objective Pembrolizumab plus platinum and pemetrexed (Pemb-Plt-PEM) combination therapy is an effective first-line treatment for advanced non-squamous non-small-cell lung cancer (NSCLC), regardless of programmed death ligand 1 expression. However, the effectiveness and feasibility of first-line Pemb-Plt-PEM therapy in elderly patients (≥75 years old) remain unclear. Therefore, this study investigated the safety and efficacy of first-line Pemb-Plt-PEM in elderly patients with nonsquamous NSCLC.
Methods We retrospectively evaluated the data of patients ≥75 years old with non-squamous NSCLC who were treated with first-line Pemb-Plt-PEM from December 2018 to December 2020 at 10 institutes in Japan. Data on patient characteristics, efficacy of pemb-Plt-PEM therapy, and the type and severity of adverse events were reviewed.
Results Thirty patients [20 men and 10 women; median age: 76 (range: 75–82) years old] were included in the analysis. The overall response rate, disease control rate, median progression-free survival (PFS), and median overall survival (OS) were 40.0%, 66.7%, and 7.5 and 24.0 months, respectively. The treatment-related deaths were caused by pneumonitis. First-line Pemb-Plt-PEM was associated with the PFS, based on the neutrophil-to-lymphocyte ratio (NLR). The PFS for low and high NLR values was 10.1 and 2.0 months, respectively. Furthermore, the sex and NLR influenced the association between Pemb-Plt-PEM and the OS. The OS for low and high NLR values was 32.8 and 2.6 months, respectively.
Conclusion First-line pemb-Plt-PEM therapy is effective and feasible in elderly patients with non-squamous NSCLC.
... Patients aged >80 years were not represented at all. This highlights a general problem in clinical intervention trials in which older patients are underrepresented [32]. Second, there is the widespread notion that endocrine therapy alone confers adequate control of high-risk PCa in older patients. ...
Background
Older men (aged ≥75 years) with high risk, non‐metastatic prostate cancer (PCa) are increasingly treated with curative therapy (surgery or radiotherapy). However, it is unclear if curative therapy prolongs life and improves health‐related quality of life (HRQoL) in this age group compared to conservative therapy, which has evolved considerably during the last decade.
Study Design
The Scandinavian Prostate Cancer Group (SPCG) 19/Norwegian Get‐Randomized Research Group‐Prostate (GRand‐P) is a randomised, two‐armed, controlled, multicentre, phase III trial carried out at study centres in Norway, Denmark, Finland, and Sweden.
Endpoints
The primary endpoints are overall survival and HRQoL (burden of disease scale, European Organisation for the Research and Treatment of Cancer [EORTC] Elderly Cancer patients). Secondary endpoints are PCa‐specific survival, metastasis‐free survival, role‐functioning scale (EORTC quality of life questionnaire 30‐item core), urinary irritative/obstructive scale (26‐item Expanded Prostate Cancer Index Composite [EPIC‐26]), bowel scale (EPIC‐26), intervention‐free survival, PCa morbidity, use of secondary and tertiary systemic therapies, mean quality‐adjusted life‐years (QALYs), and mean total healthcare costs.
Patients and Methods
A total of 980 men (aged ≥75 years) with non‐metastatic, high‐risk PCa will initially be screened with Geriatric 8 (G8) health status screening tool and Mini‐COG© brief cognitive test. Participants identified by G8 as ‘fit’ or ‘frail’ will be randomised (ratio 1:1) to either immediate curative therapy (radiotherapy or prostatectomy) or conservative therapy (endocrine therapy or observation). Participants who are unable or unwilling to participate in randomisation will be enrolled in a separate observation group. Randomised patients will be followed for 10 years.
Trial Registration
Ethics approval has been granted in Norway (457593), Denmark (H‐22051998), Finland (R23043) and Sweden (Dnr 2023‐05296‐01). The trial is registered on Clinicaltrials.org (NCT05448547).
... Randomised controlled trials (RCTs) often establish standard clinical practices. The applicability of the trial results could be compromised by the under-representation of elderly patients [6][7][8]. ...
Objective
To illustrate the status of all cancer clinical trials and characterize clinical trial enrollment disparities in the most common cancer.
Methods
Clinical trial data were extracted from ClinicalTrials.gov website. All searched clinical trials were included in the current status analysis of clinical trials on cancer. Among all the clinical trials, only trials addressing single disease sites of breast, prostate, colorectal, or lung (BPCRL) cancer were included in the age disparities analysis. The difference in median age (DMA) between the trial participant median age and the population-based disease-site-specific median age was calculated for each trial.
Results
A total of 7747 clinical trials were included in the current status analysis of clinical trials on cancer. The number of registered trials had been increasing from 2008 to 2021 (AAPC = 50.60, 95% CI 36.60, 66.00, P < 0.05). Of the 7747 trials, 1.50% (116) of the studies were clinical trials for the elderly aged 60 years or older. 322 trials were included in the age disparities analysis. For all trials, the median DMA was − 8.15 years (P25, P75, − 10.83 to − 2.98 years, P < 0.001). The median DMA were − 9.55 years (P25, P75, − 11.63 to − 7.11 years), − 7.10 years (P25, P75, − 9.80 to − 5.70 years), − 9.75 years (P25, P75, − 11.93 to − 7.35 years), 3.50 years (P25, P75, 0.60 to 4.55 years), respectively, for breast cancer, colorectal cancer, lung cancer and prostate cancer.
Conclusion
The numbers of registered clinical trials show an upward trend. Age disparities between trial participants and diagnosed disease population are present in BPCRL cancer trials and appear to be increasing over time. Equitable participation in clinical trials on the basis of age is crucial for advancing medical knowledge and evaluating the safety and efficacy of new treatments that are generalizable to aging populations.
... Feasibility was high regarding participant adherence to tele-visits, unsupervised IMT + walking, completion of activity logs and PCOMs, and retention. Enrollment was challenging, although comparable to other exercise trials in cancer [38] and higher than US National Clinical Trials in lung cancer [66], traditionally difficult to enroll [67]. Decreased intervention intensity or additional components, with compelling outcome data aligned with patient values or goals, may be needed for wider uptake. ...
Purpose
Following curative-intent therapy of lung cancer, many survivors experience dyspnea and physical inactivity. We investigated the feasibility, acceptability, safety, and potential efficacy of inspiratory muscle training (IMT) and walking promotion to disrupt a postulated “dyspnea-inactivity” spiral.
Methods
Between January and December 2022, we recruited lung cancer survivors from Kaiser Permanente Colorado who completed curative-intent therapy within 1–6 months into a phase-IIb, parallel-group, pilot randomized trial (1:1 allocation). The 12-week intervention, delivered via telemedicine, consisted of exercise training (IMT + walking), education, and behavior change support. Control participants received educational materials on general exercise. We determined feasibility a priori: enrollment of ≥ 20% eligible patients, ≥ 75% retention, study measure completion, and adherence. We assessed acceptability using the Telemedicine-Satisfaction-and-Usefulness-Questionnaire and safety events that included emergency department visits or hospitalizations. Patient-centered outcome measures (PCOMs) included dyspnea (University-of-California-San-Diego-Shortness-of-Breath-Questionnaire), physical activity (activPAL™ steps/day), functional exercise capacity (mobile-based-six-minute-walk-test), and health-related quality of life (HRQL, St.-George’s-Respiratory-Questionnaire). We used linear mixed-effects models to assess potential efficacy.
Results
We screened 751 patients, identified 124 eligible, and consented 31 (25%) participants. Among 28 participants randomized (14/group), 22 (11/group) completed the study (79% retention). Intervention participants returned > 90% of self-reported activity logs, completed > 90% of PCOMs, and attended > 90% of tele-visits; 75% of participants performed IMT at the recommended dose. Participants had high satisfaction with tele-visits and found the intervention useful. There was no statistically significant difference in safety events between groups. Compared to control participants from baseline to follow-up, intervention participants had statistically significant and clinically meaningful improved HRQL (SGRQ total, symptom, and impact scores) (standardized effect size: -1.03 to -1.30).
Conclusions
Among lung cancer survivors following curative-intent therapy, telemedicine-based IMT + walking was feasible, acceptable, safe, and had potential to disrupt the “dyspnea-inactivity” spiral. Future efficacy/effectiveness trials are warranted and should incorporate IMT and walking promotion to improve HRQL.
Trial Registration: ClinicalTrials.gov NCT05059132.
... Fortunately, this gap in the proportion has narrowed from 14.9% (1985)(1986)(1987)(1988)(1989) to 8.4% (2015-2017) [3] because the proportion of women among new cases of HNSCC has decreased by 0.6% every 5 years while the proportion of women in US clinical trials has increased 0.3% every 5 years [3]. In lung cancer, where men have a 2-3-fold higher incidence than women, the underrepresentation of women due to enrollment disparity has also been alleviated [21,22]. Therefore, sex-based participation disparity in clinical trials can be expected to be mitigated in the future. ...
We aimed to compare treatment modalities and outcomes by gender in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC). We characterized the sex-specific differences and compared the overall survival (OS) between male and female patients in a multicenter cohort of LA-HNSCC. To minimize the observed confounding, propensity score matching was utilized. The study included 445 patients; 385 (86.5%) were men and 60 (13.5%) were women. In terms of age, smoking habits, drinking habits, and primary tumor locations, there was a significant imbalance in sex before the matching. Propensity score matching yielded 60 patient pairs, with no statistical difference between the sexes in terms of their characteristics. As for the treatment strategies, there were no significant differences between the sexes before (p = 0.260) and after (p = 0.585) the propensity score matching. When comparing the survival probabilities between the sexes, OS was not significantly different in the overall (HR 1.02; 95% CI 0.59–1.76; p = 0.938) and propensity-score-matched population (HR 1.46; 95% CI 0.68–3.17; p = 0.331). These results suggest that there was no difference in prognosis by gender in the treatment modalities and outcomes of LA-HNSCC in real-world practice.
... Older patients are less likely than younger patients to receive systemic therapy or a referral to an oncologist [12], receive a lung cancer resection [13], or be administered guideline adherent treatment despite reported benefits [14]. While the median age at lung cancer patient diagnosis is 71 years [15], older patients, especially older women, are often underrepresented in clinical trials [16,17]. This may lead to inequities in treatment choice based on a lack of clinical knowledge about specific groups. ...
Introduction
: Age-related disparities in non-small cell lung cancer (NSCLC) treatment are well known, but few studies have assessed the impact of sex on treatment disparities. Disparities in guideline-adherence may explain the superior survival in women with NSCLC. Therefore, we aimed to define patient- and tumor-related factors associated with non-adherence to guidelines in NSCLC management with a special focus on sex and age.
Patients and Methods
: Patients with NSCLC who received first-line treatment at the Vaasa Central Hospital between 2016 and 2020 were included in the study. The primary outcome was guideline adherence, defined as adherent, undertreatment, or overtreatment considering performance status. A binary logistic regression model was used to calculate the adjusted odds ratio (aOR) for non-adherence to treatment guidelines depending on patient- and tumor-related factors.
Results
: 321 patients were included in the study. Non-adherence was highest in ≥75-year-old women (41.3%), followed by ≥75-year-old men (32.6%), <75-year-old men (27.6%) and lowest in women <75-year-old (19.7%) (p=0.035). Non-adherent care consisted more often of undertreatment in <75-year-old men than women (26.0% versus 12.1%) and overtreatment in <75-year-old women than men (7.6% versus 1.6%). Non-adherence was associated with stage III disease (aOR 2.21; 95% CI 1.07–4.59), poor pulmonary function (aOR 3.69, 95% CI 1.56–8.71), and Charlson Comorbidity Index 1-2 (aOR 2.09; 95% CI 1.09–4.01).
Conclusion
: Sex- and age-related disparities in guideline adherence were observed in <75-year-old men and in ≥75-year-olds. Stage III NSCLC was associated with non-adherence.
... The dataset initially included 27 007 individuals that were participants in a total of 135 clinical trials, and ECOG performance status was included. More specifics about the assembled data set can be found in the article by Pang et al. 15 Inclusion and exclusion criteria for trials and individual patients are included in Figure 1. ...
Background:
Weight loss (WL) has been associated with shorter survival in patients with advanced cancer, while obesity has been associated with longer survival. Integrating body mass index (BMI) and WL provides a powerful prognostic tool but has not been well-studied in lung cancer patients, particularly in the setting of clinical trials.
Methods:
We analysed patient data (n = 10 128) from 63 National Cancer Institute sponsored advanced non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) trials. Risk matrices were created using BMI and WL percentage, which were divided into 'grades' based on median survival. Relationships between survival, BMI and WL percentage were examined using Kaplan-Meier estimators and Cox proportional hazards (PH) models with restricted cubic splines.
Results:
For NSCLC, a twofold difference was noted in median survival between the BMI > 28 and WL ≤ 5% group (13.5 months) compared with the BMI < 20 and WL > 5% group (6.6 months). These associations were less pronounced in SCLC. Kaplan-Meier curves showed significant survival differences between grades for both NSCLC and SCLC (log-rank, P < 0.0001). In Stage IV NSCLC, Cox PH analyses with restricted cubic splines demonstrated significant associations between BMI and survival in both WL ≤ 5% (P = 0.0004) and >5% (P = 0.0129) groups, as well as in WL > 5% in Stage III (P = 0.0306). In SCLC, these relationships were more complex.
Conclusions:
BMI and WL have strong associations with overall survival in patients with advanced lung cancer, with a greater impact seen in NSCLC compared with SCLC. The integration of a BMI/WL grading scale may provide additional prognostic information and should be included in the evaluation of therapeutic interventions in future clinical trials in advanced lung cancer.
... An explanation for this discrepancy is that there is considerable heterogeneity in physiological changes that occur with aging. Furthermore, only a low number of older adult patients are enrolled in clinical trials, although enrollment disparity has been improved in older adult NSCLC patients [6]. It is difficult to predict the tolerability of general older adult patients who are more vulnerable to adverse events from systemic therapy in clinical practice. ...
Introduction
Previous studies have developed risk stratification schemas to assess systemic therapy toxicity. However, it is controversial which geriatric assessment variables should be used to assess the individual risk of severe treatment-associated toxicity in older adult patients.
Materials and methods
Patients aged ≥70 years with advanced non-small cell lung cancer (NSCLC) treated at 24 National Hospital Organization institutions completed a pre-first-line systemic therapy assessment, including patient characteristics, treatment variables, laboratory test values, and geriatric assessment variables. Patients were followed through one cycle of systemic therapy to assess grade 3 (severe) to grade 5 (death) adverse events according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
Results
In total, 348 advanced NSCLC patients with a median age of 76 years (range, 70 to 95 years) joined this prospective study. Severe adverse events ≥grade 3 occurred in 136 patients (39.1%). Predictors of hematologic toxicity were treatment variables, body mass index, body weight loss, and limitation in daily living due to dementia. These predictors provided the predictive model of hematologic toxicity ≥grade 3; 0 point (22.2%), 1 point (33.8%), 2 points (59.6%), ≥3 points (73.3%). Sex, daily living independence level, and lactate dehydrogenase levels were associated with non-hematologic toxicity ≥grade 3 in multivariate analysis. A scoring system using these predictors distinguished the risk levels of non-hematologic toxicity ≥grade 3; 0 point (6.6%), 1 point (12.2%), 2 points (39.0%), 3 points (75.0%).
Discussion
A stratification using individual extracted risk factors may be useful to predict the vulnerability to systemic therapy in older adult NSCLC patients.
... Ainsi, une étude citée en France en 2020 dans une newsletter féministe pour dénoncer le manque de femmes dans le domaine cardiovasculaire conclut en réalité qu'elles ne sont plus sous-représentées et que le biais apparent restant pour un type d'infarctus est a priori dû au fait qu'il les touche moins [Vitale et al., 2017]. De même, la part minoritaire des femmes dans les essais sur le cancer du poumon s'explique par leur moindre exposition à cette maladie et l'écart entre leur part des malades et celle des participants a peu à peu disparu parallèlement à l'augmentation de ce cancer chez elles [Pang et al., 2016]. Surtout, aucune conséquence de ces écarts historiques n'est avérée. ...
... Discrepancies in prevalence of invitation may also be due to differences in the socio-demographic characteristics of study samples since this study with national data shows important differences within socio-demographic factors. Considering race and ethnicity, we observed that Asian individuals reported the lowest prevalence of invitation to join clinical trials (2%), with no or little improvement to what observed in previous studies (Guerrero et al., 2018;Pang et al., 2016). This low prevalence may be attributed to the limited efforts dedicated to recruiting Asians specifically. ...
Clinical trials are essential to modern medicine, but several barriers, including poor communication, hamper their successful completion. We examined the prevalence and correlates of invitation to participate in clinical trials among a nationally-representative sample of US adults using survey responses from the 2020 HINTS (Cycle 5). Analyses were conducted in 2021.
Overall, 9% of respondents reported being invited to a clinical trial, a prevalence that is nearly half of previously reported rates in convenience samples recruited from health care settings. Compared to non-Hispanic Whites, Black respondents reported the higher prevalence of invitation (16.0%) whereas Asian respondents reported the lowest (2%). Prevalence of clinical trial invitation was significantly higher for the 65–74 age and the 75 + age groups. Prevalence of invitation was significantly higher among college graduates (12.0%) and lower for those residing in rural areas/small towns compared to metropolitan areas. Invitation was significantly higher among cancer patients/survivors (16.0%), patients with diabetes (11.7%) and with chronic lung disease (16.7%). Provider and patient factors there were associated with higher invitation rates included using web devices to communicate with providers or to aid health-related discussions, having a specific medical provider, and looking for health information online.
This study establishes a population-based prevalence of clinical trial communication that can be monitored as health care providers/organizations increase their focus on enrollment activities. Targeted interventions to improve communication about clinical trials are needed to address socio-demographic disparities and are particularly important for Asian patients, patients with lower income, and those living in rural areas.
... To measure enrollment of females, we used a modified version of the enrollment disparity difference (EDD), a metric which accounts for sex prevalence inequalities in the general population, initially developed to characterize enrollment disparities in lung cancer treatment RCTs, 16 and also used in a recent study of sex enrollment disparities in RCTs of acute stroke therapies. 8 For each RCT, we calculated the proportion of females we considered the GBD estimates of that country. ...
Background
Underrepresentation of females in randomized controlled trials (RCTs) limits generalizability and quality of the evidence guiding treatment of females. This study aimed to measure the sex disparities in participants' recruitment in RCTs of atrial fibrillation (AF) and determine associated factors, and to describe the frequency of outcomes reported by sex.
Methods
MEDLINE was searched to identify RCTs of AF published between January 1, 2011, and November 20, 2021, in 12 top‐tier journals. We measured the enrollment of females using the enrollment disparity difference (EDD) which is the difference between the proportion of females in the trial and the proportion of females with AF in the underlying general population (obtained from the Global Burden of Disease). Random‐effects meta‐analyses of the EDD were performed, and multivariable meta‐regression was used to explore factors associated with disparity estimates. We also determined the proportion of trials that included sex‐stratified results.
Results
Out of 1133 records screened, 142 trials were included, reporting on a total of 133 532 participants. The random‐effects summary EDD was −0.125 (95% confidence interval [CI] = −0.143 to −0.108), indicating that females were under‐enrolled by 12.5 percentage points. Female enrollment was higher in trials with higher sample size (<250 vs. >750, adjusted odds ratio [aOR] 1.065, 95% CI: 1.008–1.125), higher mean participants' age (aOR: 1.006, 95% CI: 1.002–1.009), and lower in trials conducted in North America compared to Europe (aOR: 0.945, 95% CI: 0.898–0.995). Only 36 trials (25.4%) reported outcomes by sex, and of these 29 (80.6%) performed statistical testing of the sex‐by‐treatment interaction.
Conclusion
Females remain substantially less represented in RCTs of AF, and sex‐stratified reporting of primary outcomes is infrequent. These findings call for urgent action to improve sex equity in enrollment and sex‐stratified outcomes' reporting in RCTs of AF.
... Due to the aging population, the incidence of NSCLC in the elderly (≥75 years old) is increasing (15,16). Nevertheless, elderly patients are often excluded from clinical trials because of their reduced ability to tolerate treatment (e.g., performance score [ECOG PS] ≥2), comorbidities, and potential differences in drug metabolism (17,18). A recent study showed that elderly patients receiving first-line P+C had significantly shorter PFS and OS than younger patients (PFS: 6.2 months vs. 9.7 months, P= 0.004; OS: 11 months vs. not reached, P<0.001) (19). ...
Objective
Several trials have shown that pembrolizumab plus chemotherapy was more effective in patients with advanced non-small-cell lung cancer (NSCLC) than chemotherapy monotherapy. However, whether pembrolizumab plus chemotherapy is still a better choice for first-line treatment in elderly patients (≥75 years old) remain unknown. We retrospectively compared the efficacy and safety of these two treatments in elderly patients.
Patients and Methods
We collected data of 136 elderly patients with advanced NSCLC who were treated with pembrolizumab plus chemotherapy or chemotherapy monotherapy in our hospital from 2018 to 2020. We compared the progression-free survival (PFS) and overall survival (OS) of patients and analyzed which subgroups might benefit more significantly from pembrolizumab plus chemotherapy.
Results
In total population, pembrolizumab plus chemotherapy showed superior PFS and OS than chemotherapy monotherapy (PFS: 12.50 months vs. 5.30 months, P<0.001; OS: unreached vs. 21.27 months, P=0.037). Subgroup analysis showed patients with positive PD-L1 expression, stage IV, good performance score (ECOG-PS <2), fewer comorbidities (simplified comorbidity score <9) or female patients had demonstrated a more evident OS benefit in pembrolizumab plus chemotherapy. In terms of safety, the pembrolizumab plus chemotherapy group had higher treatment discontinuation (26% vs. 5%).
Conclusions
Elderly patients using pembrolizumab plus chemotherapy achieved longer PFS and OS, but were more likely to discontinue due to adverse effects, so disease stage, PD-L1 expression, ECOG-PS and comorbidities should be considered when selecting first-line treatment.
... Due to the small number of elderly patients (≥ 75 years) with mNSCLC included in the clinical trials of immunotherapy and the issues of immunosenescence, the efficacy of PD-1-ICB among the subset of elderly patients remains unclear [13,24,25]. We chose the cut-off of 75 years as patients ≥ 75 years of age demonstrated the greatest disparity between the cancer diagnosis and the clinical trial representation [26]. ...
An immune checkpoint blockade with mAbs to PD-1 and PD-L1 is an expanding therapeutic option for mNSCLC patients. This treatment strategy is based on the use of mAbs able to restore the anti-tumor activity of intratumoral T cells inhibited by PD-1 binding to PD-L1/2 on tumor and inflammatory cells. It has been speculated that a chronic status of systemic inflammation as well as the immunosenescence physiologically occurring in elderly patients may affect the efficacy of the treatment and the occurrence of irAEs. We performed a multi-institutional retrospective study aimed at evaluating the effects of these mAbs (nivolumab or atezolizumab) in 117 mNSCLC patients younger (90 cases) and older (27 cases) than 75 years in correlation with multiple inflammatory parameters (NLR, CRP, ESR, LDH and PCT). No differences were observed when the cohorts were compared in terms of the frequency of PFS, OS, inflammatory markers and immune-related adverse events (irAEs). Similarly, the occurrence of irAEs was strictly correlated with a prolonged OS survival in both groups. On the contrary, a negative correlation between the high baseline levels of inflammatory markers and OS could be demonstrated in the younger cohort only. Overall, PD-1/PD-L1-blocking mAbs were equally effective in young and elderly mNSCLC patients; however, the detrimental influence of a systemic inflammation at the baseline was only observed in young patients, suggesting different aging-related inflammation immunoregulative effects.
... Patients over the age of 65 (≥65) constitute approximately 54% of newly diagnosed cancers and approximately 70% of cancer-related deaths [7,8]. These patients aged ≥65 years, who form the majority of clinical practice, are represented less in clinical studies than in real life [9][10][11][12][13]. Therefore, there are fewer studies and data in this patient group. ...
Purpose:
Patients over the age of 65 constitute approximately 54% of newly diagnosed cancers and approximately 70% of cancer-related deaths. These patients aged ≥65 years, who form the majority of clinical practice, are represented less in clinical studies than in real life. We designed this retrospective study to examine the treatment and response of patients to pancreatic cancer in patients over 70 years of age.
Methods:
Our study is a retrospective study that included patients from 5 centers in Turkey. Inclusion criteria were being over the age of 18 years, diagnosed with pancreatic cancer, and with ECOG performance score between 0-2. These patients were divided into two groups according to their age. The classification was made as patients over 70 years of age in the first group (geriatric group) and patients under 70 years of age (<70 age group) in the second group.
Results:
Overall survival of the <70 age group was statistically significantly longer (median 10 months vs 9.1 months p=0.027). When the patients who underwent only curative surgery were examined, the survival was statistically significant in favor of the <70 age group (median 20.96 months vs 14.5 months p=0.011). No statistically significant difference was found between the two groups in terms of the overall survival of patients with metastatic diagnosis (median 8.1 months vs 8.4 months p=0.182).
Conclusion:
The survival of patients with pancreatic cancer aged 70 and over was shorter than other age groups. While this difference was significant in patients who could undergo surgery at an early stage, it was not found in the metastatic patient group. Prospective larger-scale studies are needed to evaluate the treatment of geriatric patients better.
... This disparity is further exacerbated by underrepresentation of minorities in clinical trials for CF therapeutics (12). CF is not the only example of underrepresentation of minority populations in clinical research (13), particularly in therapeutic trials, as this also occurs in studies of other lung diseases that disproportionately affect minority groups, including asthma (14,15) and lung cancer (16). For the purpose of this research statement, we use the term "minority" to refer to racially and ethnically distinct groups who have been historically disadvantaged in the United States, including Black or African Americans, Hispanic or Latinx groups, American Indian or Alaska Native groups, and Native Hawaiians or Pacific Islanders. ...
Background: Well-designed clinical research needs to obtain information that is applicable to the general population. However, most current studies fail to include substantial cohorts of racial/ethnic minority populations. Such underrepresentation may lead to delayed diagnosis or misdiagnosis of disease, wide application of approved interventions without appropriate knowledge of their usefulness in certain populations, and development of recommendations that are not broadly applicable.
Goals: To develop best practices for recruitment and retention of racial/ethnic minorities for clinical research in pulmonary, critical care, and sleep medicine.
Methods: The American Thoracic Society convened a workshop in May of 2019. This included an international interprofessional group from academia, industry, the NIH, and the U.S. Food and Drug Administration, with expertise ranging from clinical and biomedical research to community-based participatory research methods and patient advocacy. Workshop participants addressed historical and current mistrust of scientific research, systemic bias, and social and structural barriers to minority participation in clinical research. A literature search of PubMed and Google Scholar was performed to support conclusions. The search was not a systematic review of the literature.
Results: Barriers at the individual, interpersonal, institutional, and federal/policy levels were identified as limiting to minority participation in clinical research. Through the use of a multilevel framework, workshop participants proposed evidence-based solutions to the identified barriers.
Conclusions: To date, minority participation in clinical research is not representative of the U.S. and global populations. This American Thoracic Society research statement identifies potential evidence-based solutions by applying a multilevel framework that is anchored in community engagement methods and patient advocacy.
Background
Racial and ethnic minorities remain underrepresented in gynecologic cancer clinical trials despite disproportionately worse oncologic outcomes. Research shows differential racial enrollment patterns due to comorbidity-based exclusion criteria (CEC). Our objective was to evaluate contemporary trends in CECs among NCI-sponsored gynecologic cancer clinical trials and protocol adherence to broadened eligibility criteria guidelines as an assessment of equitable enrollment access.
Methods
The ClinicalTrials.gov registry was queried for NCI-sponsored gynecologic cancer clinical trials (1994-2021). Study characteristics and CECs were abstracted from protocols. Descriptive statistics and temporal trends were calculated using chi-square testing with STATA v17 software.
Results
Among 279 clinical trials identified, 65% completed enrollment, 53% were Phase II, and 48% focused on ovarian cancer. Pharmaceutical agents (85%) were the primary therapeutic interventions.
Several inequitably restrictive exclusion criteria increased over time such as hepatitis infection (17% in 1994-2000 vs 49% in 2015-2021, p < .001) and cardiovascular disease (47% in 1994-2000 vs 66% in 2015-2021, p = .002). A previously rare exclusion, “mental illness/social situations,” dramatically increased from 5% to 51% (p < .001) over three decades.
Adherence to broadened eligibility criteria recommendations was mixed. Renal function, cardiovascular disease, and performance status criteria were not broadened but HIV, prior/concurrent malignancies, and brain metastasis criteria were.
Conclusions
Some, but not all, of the known restrictive CECs have increased in gynecologic cancer clinical trial design, despite calls for improving racial and ethnic minority representation. While exclusion criteria are critical for trial safety, they must be carefully considered given the differential racial impact on eligibility.
Simple Summary
Lung cancer is the leading cause of cancer-related mortality among older adults, but older adults experience age-related disparities in treatment outcomes, clinical trial representation, and guideline-concordant care. This review addresses critical factors contributing to these disparities, outlining age-specific considerations to optimize management of medical and supportive care needs and cancer-directed therapy selection. Key recommendations include comprehensive geriatric assessment, individualized treatment planning, and improved resource allocation to ensure older adults receive equitable and effective care.
The potential of real‐world data to inform clinical trial design and supplement control arms has gained much interest in recent years. The most common approach relies on reproducing control arm outcomes by matching real‐world patient cohorts to clinical trial baseline populations. However, recent studies pointed out that there is a lack of replicability, generalisability, and consensus. In this article, we propose a novel approach that aims to explore and examine these discrepancies by concomitantly investigating the impact of selection criteria and operations on the measurements of outcomes from the patient data. We tested the approach on a dataset consisting of small‐cell lung cancer patients receiving platinum‐based chemotherapy regimens from a real‐world data cohort (n = 223) and six clinical trial control arms (n = 1224). The results showed that the discrepancy between real‐world and clinical trial data potentially depends on differences in both patient populations and operational conditions (e.g., frequency of assessments, and censoring), for which further investigation is required. Discovering and accounting for confounders, including hidden effects of differences in operations related to the treatment process and clinical trial study protocol, would potentially allow for improved translation between clinical trials and real‐world data. Continued development of the method presented here to systematically explore and account for these differences could pave the way for transferring learning across clinical studies and developing mutual translation between the real‐world and clinical trials to inform clinical study design.
Background
Increased engagement with community-based practices is a promising strategy for increasing clinical trials access of diverse patient populations. In this study we assessed the ability to utilize a patient-advocacy organization led clinical network to engage diverse practices as field sites for clinical research.
Methods
GO2 for Lung Cancer led recruitment efforts of 17 field sites from their Centers of Excellence in Lung Cancer Screening Network for participation in an implementation-effectiveness trial focused on smoking cessation integration into screening programs for lung cancer. Sites were engaged by one of three methods: 1) Pre-Grant submission of letters of support, 2) a non-targeted study information dissemination campaign to network members, and 3) proactive, targeted outreach to specific centers informed by previously submitted network member data. Detailed self-reported information on barriers to participation was collected from centers that declined to join the study.
Results
Of 17 total field sites, 16 were recruited via the targeted outreach campaign and 1 via pre-grant letter of support submission. The sites covered 13 states and 4 United States geographic regions, were varied in annual screening volumes and years of screening program experience and were predominantly community-based practices (10 of 17 sites). The most reported reason (by 33% of sites) for declining to participate as a field site was inadequate staffing bandwidth for trial activities. This was especially true in community-based programs among which it was reported by 45% as a reason for declining.
Conclusions
Our results suggest that this model of field site recruitment leveraging an existing partnership between an academic research team and an informal clinical network maintained by a disease-specific patient advocacy organization can result in engagement of diverse, community-based field sites. Additionally, reported barriers to participation by sites indicate that solutions centered around providing additional resources to enable greater capacity for site staff may increase community-practice participation in research.
Abstract
Background: Lung cancer represents the second most prevalent cause of cancer, and the most common cause of cancer-related mortality among men and women in the United States. Over half the patients diagnosed with lung cancer are over the age of 70 years, and addressing cancer treatment in older adults presents distinct challenges. Over the past two decades, substantial progress has been made in the field of lung cancer treatment, particularly with the advent of immunotherapy and targeted therapies in the management of NSCLC. These treatment modalities have demonstrated effectiveness and a favorable tolerance profile, even among elderly individuals.
Objectives: The primary aim of this review is to provide a comprehensive summary of key clinical trials concerning the management of lung cancer in the elderly. Furthermore, it underscores the importance of assessing frailty and incorporating Comprehensive Geriatric Assessment (CGA) in the treatment decisions pertaining to older adults with lung cancer.
Summary: Numerous clinical trials have investigated the benefits of these treatments in fit older adults, with some trials specifically focusing on geriatric populations. In all cases, the results have shown favorable treatment outcomes. It is essential to assess for frailty and adopt a CGA tool to accurately assess a patient’s suitability for treatment, allowing for a more thorough evaluation of an elderly individual’s functional status and suitability for treatment. This approach not only predicts the tolerability and efficacy of treatment but also serves as a valuable predictor of potential treatment-related toxicities. With the advent of new therapies, there is a greater opportunity to offer treatment to older adults with lung cancer.
Background
In the United States, less than 5% of all adult cancer patients enroll in clinical trials. Few studies explore participation in cancer clinical trials at safety net hospitals, which disproportionately care for minoritized, low-income, uninsured, and underinsured populations. Our study aims to investigate disparities in clinical trial discussions and enrollment among lung cancer patients at Boston Medical Center, the largest safety net hospital in New England.
Methods
We included 1121 patients diagnosed with lung cancer between January 2015 and December 2020. Electronic Medical Records (EMR) were queried, and patients were categorized into three groups: (1) clinical trial discussed and the patient enrolled, (2) clinical trial discussed but the patient not enrolled, and (3) clinical trial not discussed. Sociodemographic variables such as age, gender, race, ethnicity, city, primary language, median household income, medical insurance type, and education level were also collected. Chi-squared, t test, and multivariate regression analysis was done using SPSS version 26.0.
Results
Of the 1121 patients, clinical trials were discussed in 141 patients (12.6%), of which 22 (15.6%) were enrolled. Clinical trial discussions were conducted more with younger patients (68.19 vs 71.37, p = .001), but on multivariate analysis there was no significant difference (OR = 1.023; 95% CI 0.998-1.048; p = .068). There was no significant difference in clinical trial discussion or enrollment between the other sociodemographic factors.
Conclusion
Additional study of barriers to cancer clinical trial discussion and enrollment at safety net institutions can serve as a prerequisite to ameliorating racial disparities observed on a national scale.
Background
There are more than 18 million cancer survivors in the United States. Yet, survivors of color remain under-represented in cancer survivorship research (Saltzman et al. in Contemp Clin Trials Commun 29:100986, 2022; Pang et al. in J Clin Oncol 34:3992–3999, 2016; Lythgoe et al. in Prostate Cancer Prostatic Dis 24:1208–1211, 2021). Our long-term goal is to enroll and follow a cohort of historically under-represented cancer survivors, to better understand modifiable risk factors that influence clinical and quality of life outcomes in these populations. Towards that goal, we describe herein how we applied community-based participatory research approaches to develop inclusive study materials for enrolling such a cohort.
Methods
We implemented community engagement strategies to inform and enhance the study website and recruitment materials for this cohort including: hiring a dedicated engagement coordinator/community health educator as a member of our team; working with the Helen Diller Family Comprehensive Cancer Center Office of Community Engagement (OCE) and Community Advisory Board members; presenting our educational, research, and study recruitment materials at community events; and establishing a community advisory group specifically for the study (4 individuals). In parallel with these efforts, 20 semi-structured user testing interviews were conducted with diverse cancer survivors to inform the look, feel, and usability of the study website.
Results
Engagement with community members was a powerful and important approach for this study’s development. Feedback was solicited and used to inform decisions regarding the study name (eat move sleep, EMOVES), logo, study website content and imagery, and recruitment materials. Based on community feedback, we developed additional educational materials on healthy groceries and portion size in multiple languages and created a study video.
Conclusions
Including an engagement coordinator as a permanent team member, partnering with the institutional community outreach and engagement resources (i.e., OCE), and allocating dedicated time and financial support for cultivating relationships with stakeholders outside the university were critical to the development of the study website and materials. Our community guided strategies will be tested as we conduct enrollment through community advisor networks and via the state cancer registry.
Abstract
Background: Lung cancer represents the second most prevalent cause of cancer, and the most common cause of cancer-related mortality among men and women in the United States. Over half the patients diagnosed with lung cancer are over the age of 70 years, and addressing cancer treatment in older adults presents distinct challenges. Over the past two decades, substantial progress has been made in the field of lung cancer treatment, particularly with the advent of immunotherapy and targeted therapies in the management of NSCLC. These treatment modalities have demonstrated effectiveness and a favorable tolerance profile, even among elderly individuals.
Objectives: The primary aim of this review is to provide a comprehensive summary of key clinical trials concerning the management of lung cancer in the elderly. Furthermore, it underscores the importance of assessing frailty and incorporating Comprehensive Geriatric Assessment (CGA) in the treatment decisions pertaining to older adults with lung cancer.
Summary: Numerous clinical trials have investigated the benefits of these treatments in fit older adults, with some trials specifically focusing on geriatric populations. In all cases, the results have shown favorable treatment outcomes. It is essential to assess for frailty and adopt a CGA tool to accurately assess a patient’s suitability for treatment, allowing for a more thorough evaluation of an elderly individual’s functional status and suitability for treatment. This approach not only predicts the tolerability and efficacy of treatment but also serves as a valuable predictor of potential treatment-related toxicities. With the advent of new therapies, there is a greater opportunity to offer treatment to older adults with lung cancer.
Keywords
Geriatric
Elderly
Older adults
Comprehensive Geriatric Assessment
Lung cancer
Non-small cell lung cancer
Lung cancer screening
Surgical resection
Stereotactic body radiation therapy
Chemoradiation therapy
Immunotherapy
Targeted therapy
Palliative care
Symptom management
PURPOSE: To investigate the enrollment success rate of cancer clinical trials conducted in 2008-2019 and various factors lowering the enrollment success rate.
METHODS: This is a cross-sectional study with clinical trial information from the largest registration database ClinicalTrials.gov. Enrollment success rate was defined as actual enrollment greater or equal to 85% of the estimated enrollment goal. The association between trial characteristics and enrollment success was evaluated using the multivariable logistic regression.
RESULTS: A total of 4,004 trials in breast, lung, and colorectal cancers were included. The overall enrollment success rate was 49.1%. Compared with 2008-2010 (51.5%) and 2011-2013 (52.1%), the enrollment success rate is lower in 2014-2016 (46.5%) and 2017-2019 (36.4%). Regression analyses found trial activation year, phase I, phase I/phase II, and phase II (v phase III), sponsor agency of government (v industry), not requiring healthy volunteers, and estimated enrollment of 50-100, 100-200, 200, and >500 (v 0-50) were associated with a lower enrollment success rate (P < .05). However, trials with placebo comparator, ≥5 locations (v 1 location), and a higher number of secondary end points (eg, ≥5 v 0) were associated with a higher enrollment success rate (P < .05). The AUC for prediction of the final logistic regression models for all trials and specific trial groups ranged from 0.69 to 0.76.
CONCLUSION: This large-scale study supports a lower enrollment success rate over years in cancer clinical trials. Identified factors for enrollment success can be used to develop and improve recruitment strategies for future cancer trials.
Background:
Disparities within clinical trial enrollment are well-documented, reducing the generalizability of results. Although nearly 30 years have passed since Congress passed the NIH Revitalization Act to encourage the participation of minoritized populations in clinical trials, these patients continue to be underrepresented. This study aimed to investigate lung cancer clinical trial enrollment disparities for race/ethnicity, sex, and age.
Methods:
We queried the National Institutes of Health: US National Library of Medicine database of clinical trials for all US-based lung cancer clinical trials completed between 2004 and 2021 and collected data on race and ethnicity, gender, and age breakdown. This data was compared to Surveillance, Epidemiology, and End Results (SEER) database data. Independent sample t-tests and Kruskal-Wallis's approach were used to analyze the data.
Results:
Of 311 eligible trials with exclusive US enrollment, 136 (44%) reported race and ethnicity breakdown for the patient cohort representing 9869 patients. Hispanic, Non-Hispanic American Indian/Alaska Native, Non-Hispanic Black, and Non-Hispanic Unreported participants were underrepresented (p = 0.001, p = 0.005, p = 0.014, p = 0.002, respectively). Non-Hispanic White participants were overrepresented (p = 0.018). Disparities worsened from 2017 to 2021 for Hispanic patients (p = 0.03). No significant differences were found for sex or age.
Conclusions:
Disparities for clinical lung cancer trial enrollment have not shown statistically significant improvement since 2004, and representation remains unequal, especially for racial and ethnic minorities.
The under-representation of racial, sexual, and gender minorities in cancer clinical trials has long been a deficit in clinical cancer research. This review aims to survey current literature to determine the participation of minorities in the United States in lung cancer clinical trials and to find educational methods that have been studied and researched in order to improve patient clinical trial enrollment. A literature search of relevant articles published since 2015 was conducted using PubMed and Google Scholar. Clinical trials conducted in the United States from Clinicaltrials.gov were also collected to determine minority patient enrollment in lung cancer clinical trials. The results of the literature search yielded 6 relevant articles about racial minority representation in lung cancer clinical trials and one relevant article about LGBTQ+ minority representation in cancer clinical trials. Collectively, the literature highlighted the under-representation of racial minorities (such as Black, Hispanic, and American Indian) in clinical trials. Many articles showed that disparities in enrollment were less significant for Asian patients with lung cancer. However, many articles did not mention minorities like Middle Eastern/North Africans and failed to mention the lack of distinguishment of South Asian minorities from Pacific Asian minorities. The findings of this literature review support the idea that current lung cancer clinical trials lack representation of minority patient populations in the United States. The inclusion of racial, sexual, and gender diversity in clinical trial patient populations will aid providers in determining appropriate therapeutics and could potentially improve lung cancer outcomes. Future directions for improving diversity in lung cancer clinical trial enrollment include the utilization of various educational tools to increase minority patient participation in trials, the inclusion of detailed demographic data in cancer clinical trial analysis, and the recruitment of providers and research staff from various minorities to conduct cancer clinical trials.
Introduction:
Half of patients with limited stage small cell lung cancer (LS SCLC) are >70 years, but account for <20% of participants in most trials. Comorbidities, reduced organ- and physical function might lead to more treatment toxicity and population-based studies indicate that fewer older than younger LS SCLC patients receive standard chemoradiotherapy, although there is limited evidence for such a policy.
Methods:
We compared baseline characteristics, comorbidity, survival, treatment completion, toxicity, health related quality of life (HRQoL) and treatment outcomes between patients >70 and <70 years in an open label randomized phase II trial comparing twice-daily thoracic radiotherapy (TRT) of 45 Gy in 30 fractions with 60 Gy in 40 fractions in LS SCLC. All patients received concurrent platinum/etoposide chemotherapy.
Results:
170 patients who were >18 years and had performance status (PS) 0-2 were randomized. Of these, 53 patients (60 Gy:25, 45 Gy:28) were >70 years and 117 (60 Gy:64, 45 Gy:53) were younger. There were no significant differences in baseline characteristics, treatment completion rates, toxicity, or response rates across age groups. HRQoL mean scores was similar during year one, but older patients reported more decline on functional scales than younger patients during year two. OS was significantly shorter for older patients while there was no significant difference in PFS or TTP.
Conclusion:
Patients >70 years tolerated concurrent twice daily chemoradiotherapy and achieved similar disease control as younger patients, indicating that older patients should receive the same treatment as younger patients.
Importance:
Older age may be accompanied by changes in the pharmacokinetics or pharmacodynamics or both of medications that can result in altered safety and efficacy profiles.
Objective:
To assess representation of older adults in clinical trials of new drug applications (NDAs) and biologics license applications (BLAs).
Design, setting, and participants:
This cross-sectional study analyzed US Food and Drug Administration (FDA) data for NDAs and BLAs approved from 2010 through 2019. Age distribution of clinical trial participants was compared with age distribution of the US population with the disease or disorder (prevalent population). Data were from adults enrolled in registration trials for depression, heart failure, insomnia, non-small cell lung cancer (NSCLC), nonvalvular atrial fibrillation (NVAF) stroke prevention, osteoporosis, and type 2 diabetes or adults sampled from US prevalent population in community-dwelling health data. Data were analyzed from November 2020 to February 2021.
Exposures:
Trial enrollment.
Main outcomes and measures:
Representativeness of trial populations was assessed by the participation to prevalence ratio (PPR) defined as the percentage of patients by age group among clinical trial participants to the percentage of patients by age group among US prevalent population.
Results:
Data from 166 clinical trials (229 558 participants) for 44 NDAs and BLAs were analyzed. The most consistent finding was the limited enrollment of the oldest age groups, namely those 75 years and above for type 2 diabetes and NSCLC, and 80 years and above for NVAF stroke prevention, insomnia, heart failure, and osteoporosis. Adults aged 60 to 74 years were enrolled in equal or greater proportion than the US prevalent population.
Conclusions and relevance:
In this cross-sectional study, underrepresentation of the oldest adults existed during evaluation of new drugs and biologics, yet the older adults may represent significant proportions of the treatment population. Closing the representation gap between clinical trial enrollment and potential treatment populations is essential for safe and effective use of new drugs and biologics.
Introduction
Pembrolizumab became available in Japan in February 2017 for first-line monotherapy of unresectable advanced/metastatic non-small cell lung cancer (NSCLC) with programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) ≥50%. This retrospective chart review study aimed to describe real-world clinical outcomes of first-line pembrolizumab monotherapy, including for patients ≥75 years old, who are under-represented in clinical trials.
Methods
We identified patients (≥20 years old) at 23 sites initiating first-line pembrolizumab monotherapy from 1-July-2017 to 20-December-2018 for stage IIIB/IIIC/IV NSCLC with PD-L1 TPS ≥50% and ECOG performance status of 0-2 or unknown. Patients with actionable genomic alterations (EGFR/ALK/ROS1/BRAF) and clinical trial participants were excluded. Time-to-event outcomes were estimated with Kaplan-Meier, with data cutoff 30-September-2019.
Results
Of 441 eligible patients (78% men), 303 (69%) were <75 and 138 (31%) were ≥75 years old; median age was 70. With median follow-up of 13.5 months, median overall survival (OS) was not reached (NR); 12- and 24-month OS rates were 72% and 58%, respectively. For ages <75 and ≥75 years, median OS was NR and 23.5 months (95% CI, 16.2-NR), respectively; 12-month OS rates were 74% and 67%; 24-month OS rates were 62% and 48%, respectively. Median real-world progression-free survival was similar in the two age groups (10.1 and 9.5 months, respectively), as was median real-world time on treatment with pembrolizumab (5.7 and 5.6 months).
Conclusions
These findings complement clinical trial results, adding real-world evidence supporting benefits of first-line pembrolizumab monotherapy for advanced NSCLC with PD-L1 TPS ≥50%, including for patients ≥75 years old.
Purpose of Review
This review aspires to summarize the landmark advancements in the management of the non-small cell lung cancer (NSCLC), both historically and contemporarily with special focus in older adults.
Recent Findings
The past two decades have witnessed remarkable improvements in the diagnosis and management of lung cancer. Screening recommendations now facilitate earlier diagnosis in high-risk individuals, PET/CT scans have improved radiologic accuracy in identifying sites of disease, and surgical management with minimally invasive techniques has rendered surgery safer in those with limited physiologic reserve. Radiation enhancements, especially radiosurgery, have extended the reach and safety of radiation among high-risk populations. Finally, the revolution in precision medicine with identification of numerous actionable mutations, the advent of immunotherapy, and enhanced supportive care have revolutionized the outcomes in patients with advanced lung cancer.
Summary
Older adults who represent a majority of patients battling lung cancer have not benefitted to the same extent as their younger counterparts. This special population is only expected to grow in coming days. Hence, addressing major gaps in the management of older adults with NSCLC and optimizing the care are much needed.
Importance:
There is substantial evidence demonstrating racial disparities in the survival outcomes of patients with head and neck cancer. The reporting and representation of race and ethnicity in cancer trials is crucial for generalizability of trial results to patient care and reduction of racial health disparities in head and neck cancers. Racial disparities in oncologic outcomes across various therapeutic interventions may only manifest when diverse races are appropriately represented in trials.
Objective:
To characterize the reporting and representation of race and ethnicity in head and neck cancer clinical trials.
Evidence review:
A systematic search of published trials and those available on ClinicalTrials.gov was conducted to identify 3973 studies from 2010 to 2020. Title, abstract, and full-text review yielded 155 trials for data extraction of patient demographics. Year of publication, type of intervention, publication source, and funding source were also collected. Race and ethnicity data were compared with Surveillance, Epidemiology, and End Results (SEER) Program cancer registry data.
Findings:
Of the 155 included studies, only 89 (57%) reported race or ethnicity. Only 81 (52%) of the studies reported detailed classification of race or ethnicity per the US Census Bureau classification scheme. Race and ethnicity reporting varied considerably with year of publication, type of intervention, data source, and funding source. Studies in the latter half of the decade were more likely to report race or ethnicity (odds ratio, 2.78; 95% CI, 1.33-5.80), with the highest number in 2019 (24 of 30 [80%] trials), followed by 2020 (20 of 29 [69%] trials). Among the possible interventions, trials on therapeutic chemoradiation most frequently reported race or ethnicity (11 of 12 [92%]), followed by supportive drug trials (22 of 31 [71%]), and then therapeutic chemotherapy trials (28 of 48 [58%]). When compared with SEER data, race and ethnicity distribution in clinical trials showed fewer Black patients (10% vs 8%) and Asian or Pacific Islander patients (6% vs 2%).
Conclusions and relevance:
In this systematic review, nearly half of head and neck cancer trials in the past decade did not report the race or ethnicity of participants. Participation of Black and Asian or Pacific Islander patients does not adequately reflect the US population's head and neck cancer demographics, limiting the generalizability of trial results and adding to racial health disparities in patients with head and neck cancers.
Purpose
We aim to describe reporting and representation of minority patient populations in immune checkpoint inhibitor (ICI) clinical trials and assess predictors of enrollment disparity.
Methods
Trial-level data were acquired from eligible phase II/III trials. Population-based estimates were acquired from the SEER 18 and Global Burden of Disease incidence databases. Trials reporting race, age, and sex were summarized using descriptive statistics. Enrollment-incidence ratio (EIR) was used to assess representation of subgroups. Average annual percentage change (AAPC) in EIR was calculated using Joinpoint Regression Analysis. Trial-level characteristics associated with EIR were assessed using multivariable linear regression.
Results
107 trials with 48,095 patients were identified. Participation of Black, White, Asian, Native American, Pacific Islander and Hispanic participants was reported in 65 (61%), 77 (72%), 68 (64%), 40 (37%) and 24 trials (22%) respectively. Subgroup analyses of clinical outcomes by race, age and sex were reported in 17 (22%), 62 (78%) and 57 (57%) trials respectively. Women (trial proportion [TP]: 32%; EIR: 0.90 [95% CI: 0.84-0.96]), patients aged ≥65 years (TP: 42%; EIR: 0.78 [95% CI: 0.72-0.84]), Black participants (TP: 1.9%; EIR: 0.17 [95% CI: 0.13-0.22]) and Hispanics (TP: 5.9%; EIR: 0.67 [95% CI: 0.53-0.82]) were underrepresented. Representation of Black patients decreased significantly from 2009-2020 (APC: -23.13). Black participants were significantly underrepresented in phase III trials (p<0.001).
Conclusion
The reporting of participation by racial/ethnic subgroup categories is inadequate and women, older adults, and racial/ethnic minorities are significantly underrepresented in ICI clinical trials.
Nivolumab was the first immune checkpoint inhibitor approved for use in advanced non-small cell lung cancer (NSCLC). This noninterventional, prospective cohort study investigates real-world effectiveness of nivolumab in pretreated NSCLC patients in Germany (Enlarge-Lung/CA209-580). Patients with squamous (SQ) or nonsquamous (NSQ) NSCLC previously treated for locally advanced or metastatic (stage IIIB/IV) disease received nivolumab according to the current Summary of Product Characteristics. Overall survival (OS) was the primary endpoint. Of 907 patients enrolled, 660 patients who were followed for at least 12 months across 79 study centers in Germany, were analyzed. Median OS was 11.2 months [95% confidence interval (CI), 9.1-12.9]; outcomes for the 418 patients with NSQ histology [13.1 mo (95% CI, 10.6-15.6)] were more favorable than outcomes for the 242 patients with SQ histology [8.9 mo (95% CI, 6.4-11.3)]. Patients' age, presence of distant or brain metastases, or line of therapy did not affect outcomes; however, patients with poor performance status (ECOG-PS ≥2, n=80) had shorter median OS [4.7 mo (95% CI, 3.1-5.4)]. This study represents one of the largest real-world cohorts providing outcomes of nivolumab in pretreated NSCLC. The results match well with the published evidence from pivotal clinical trials and demonstrate clinical effectiveness of nivolumab in advanced NSCLC.
Introduction:
We conducted a bibliometric analysis to determine the most impactful articles in the oncologic management of elderly cancer patients.
Material and methods:
We searched Web of Science papers with six keywords: "geriat*" OR "older patient*" OR "older adult*" OR "elderly" and "*cancer" OR "oncolog*". We identified and analyzed the top 100 most-cited articles and abstracted information on topic, journal, first author, year, institution, level of evidence, and the adjusted citation index.
Results:
Of the 100 most-cited papers, 62 had at least one author from the United States of America. Of the 62 United States papers, 18 had at least one author from Harvard University and 14 had authors from the National Institutes of Health. Among the 50 authors who contributed to the most-cited papers, Hurria is the most prolific author, with nine papers. Lung, breast, and colorectal cancers are the most studied cancer types, and the Geriatric 8 scale is the most studied scale.
Conclusions:
Our study is the first to analyze the top 100 most-cited studies in geriatric oncology. By comprehensively identifying the authors, institutes, journals, and the levels of evidence of these studies, we have created an easily accessible resource for practicing physicians to reference within this important area of oncology.
Outcomes in electronic health records (EHR)-derived cohorts can be compared to similarly treated clinical trial cohorts to estimate the efficacy-effectiveness gap, the discrepancy in performance of an intervention in a trial compared to the real world. However, because clinical trial data may only be available in the form of published summary statistics and Kaplan-Meier curves, survival data reconstruction methods are needed to recreate individual-level survival data. Additionally, marginal moment-balancing weights can adjust for differences in the distributions of patient characteristics between the trial and EHR cohorts. We evaluated bias in hazard ratio (HR) estimates by comparing trial and EHR cohorts using survival data reconstruction and marginal moment-balancing weights through simulations and analysis of real-world data. This approach produced nearly unbiased HR estimates. In an analysis of overall survival for patients with metastatic urothelial carcinoma treated with gemcitabine-carboplatin captured in the nationwide Flatiron Health EHR-derived de-identified database and patients enrolled in a trial of the same therapy, survival was similar in the EHR and trial cohorts after using weights to balance age, sex, and performance status (HR = 0.93, 95% confidence interval (0.74, 1.18)). Overall, we conclude that this approach is feasible for comparison of trial and EHR cohorts and facilitates evaluation of outcome differences between trial and real-world populations.
Differences in patient characteristics, including age, sex, and race influence the safety and effectiveness of drugs, biologic products, and medical devices. Here we provide a summary of the topics discussed during the opening panel at the 2018 Johns Hopkins Center for Excellence in Regulatory Science and Innovation symposium on Assessing and Communicating Heterogeneity of Treatment Effects for Patient Subpopulations: Challenges and Opportunities. The goal of this session was to provide a brief overview of FDA‐regulated therapeutics, including drugs, biologics and medical devices, and some of the major sources of heterogeneity of treatment effects (HTE) related to patient demographics, such as age, sex and race. The panel discussed the US Food and Drug Administration's role in reviewing and regulating drugs, devices, and biologic products and the challenges associated with ensuring that diverse patient populations benefit from these therapeutics. Ultimately, ensuring diverse demographic inclusion in clinical trials, and designing basic and clinical research studies to account for the intended patient population's age, sex, race, and genetic factors among other characteristics, will lead to better, safer therapies for diverse patient populations.
Background: Older adults are under-represented in cancer clinical trials. However, it remains unclear which types of trials under-enroll aging patients. We aimed to identify associations between trial characteristics and disparate enrollment of older adults onto trials sponsored by the Alliance for Clinical Trials in Oncology (Alliance).
Methods: Actual age ≥ 65 percentage and trial data were extracted from the Alliance closed study list. Each trial, based on its cancer type and years of enrollment, was assigned an expected age ≥ 65 percentage extracted from the Surveillance, Epidemiology, and End Results (SEER) US population-based database. Enrollment disparity difference (EDD), the difference between the expected age ≥ 65 percentage and the actual age ≥ 65 percentage, was calculated for each trial. Linear regression determined trial variables associated with larger EDDs and variables with an overall association p-value <0.20 were included in a multivariable fixed-effects linear model.
Results: The median age of 66,708 patients across 237 trials was 60 years (range 18–102). The average actual age ≥ 65 percentage enrolled per trial was lower than each trial's expected age ≥ 65 percentage average (39% vs. 58%; EDD 19, 95% CI 17.1–21.3%, p < 0.0001). In multivariable analyses, non-genitourinary (GU) cancer types (p < 0.001), trimodality+ trials (estimate 8.78, 95%CI 2.21–15.34, p = 0.009), and phase 2 trials (estimate 4.43 95% CI -0.06-8.91; p = 0.05) were all associated with larger EDDs.
Conclusions: Disparate enrollment of older adults is not equal across cancer trials. Future strategies to improve older adult inclusion should focus on trial types associated with the highest disparate enrollment.
Objective
The Food and Drug Administration and the National Institutes of Health (NIH) have asserted that diverse demographic representation in clinical trials is essential. In light of these federal guidelines, the objective of this study is to assess the racial, ethnic, and gender demographics of patients enrolled in clinical trials registered with the NIH that evaluate chronic rhinosinusitis with nasal polyposis (CRSwNP) relative to the demographics of the US population.
Study Design
Cross-sectional study.
Setting
Not applicable.
Methods
ClinicalTrials.gov was queried to identify all prospective clinical trials for CRSwNP. Individual study and pooled data were compared with national US census data.
Results
Eighteen studies were included comprising 4125 patients and evaluating dupilumab, mepolizumab, omalizumab, fluticasone/OptiNose, MediHoney, mometasone, and SINUVA. Women constituted 42.7% of clinical trial participants. Of the 4125 participants, 69.6% identified as White, 6.6% as Black, 20.8% as Asian, 0.1% as Pacific Islander, 0.4% as American Indian, 8.0% as Hispanic, and 2.4% as other. The racial, ethnic, and gender composition of the pooled study population differs significantly from national US census data, with underrepresentation of Black, Hispanic, Pacific Island, and American Indian individuals, as well as females ( P < .05).
Conclusion
The racial, ethnic, and gender demographics of patients enrolled in CRSwNP clinical trials registered with the NIH differ significantly from the demographics of the US population, despite federal guidelines advising demographically representative participation. Proactive efforts to enroll participants that better represent anticipated treatment populations should be emphasized by researchers, institutions, and editorial boards.
Background Enrollment rates onto cancer clinical trials are low and reflect a small subset of the population of which even fewer participants come from populations of racial or ethnic diversity or low socioeconomic status. There is a need to increase enrollment onto cancer clinical trials with a focus on recruitment of a diverse, underrepresented patient population. Objective To use the electronic medical record (EMR) to understand the eligibility and enrollment rates for all available cancer trials in the ambulatory care setting at an urban safety net hospital to identify specific strategies for enhanced accrual onto cancer clinical trials of diverse and underserved patients. Methods A clinical trial screening note was created for the EMR by the clinical trials office at an urban safety net hospital. 847 cancer clinical trial screening notes were extracted from the EMR between January 1, 2010 and December 31, 2010. During that time, 99 cancer trials were registered for accrual, including clinical treatment, survey, data repository, imaging, and symptom management trials. Data on eligibility, enrollment status, and relationship to sociodemographic status were compared. Limitations This is a single-institution and retrospective study. Conclusion The findings demonstrate that a formal process of tracking cancer clinical trial screens using an EMR can document baseline rates of institution-specific accrual patterns and identify targeted strategies for increasing cancer clinical trial enrollment among a vulnerable patient population. Offering nontreatment trials may be an important and strategic method of engaging this vulnerable population in clinical research.
Esteban Gonzalez Burchard and colleagues explore how making medical research more diverse would aid not only social justice but scientific quality and clinical effectiveness, too.
Screening logs have the potential to help oncology clinical trial programs at the site level, as well as trial leaders, address enrollment in real time. Such an approach could be especially helpful in improving representation of racial/ethnic minority and other underrepresented populations in clinical trials.
The National Cancer Institute Community Cancer Centers Program (NCCCP) developed a screening log. Log data collected from March 2009 through May 2012 were analyzed for number of patients screened versus enrolled, including for demographic subgroups; screening methods; and enrollment barriers, including reasons for ineligibility and provider and patient reasons for declining to offer or participate in a trial. User feedback was obtained to better understand perceptions of log utility.
Of 4,483 patients screened, 18.4% enrolled onto NCCCP log trials. Reasons for nonenrollment were ineligibility (51.6%), patient declined (25.8%), physician declined (15.6%), urgent need for treatment (6.6%), and trial suspension (0.4%). Major reasons for patients declining were no desire to participate in trials (43.2%) and preference for standard of care (39%). Major reasons for physicians declining to offer trials were preference for standard of care (53%) and concerns about tolerability (29.3%). Enrollment rates onto log trials did not differ between white and black (P = .15) or between Hispanic and non-Hispanic patients (P = .73). Other races had lower enrollment rates than whites and blacks. Sites valued the ready access to log data on enrollment barriers, with some sites changing practices to address those barriers.
Use of screening logs to document enrollment barriers at the local level can facilitate development of strategies to enhance clinical trial accrual.
Evidence from the US National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database suggests that the incidence of advanced breast cancer in young women is increasing.
To quantify this trend and analyze it as a function of stage at diagnosis, race/ethnicity, residence, and hormone receptor status.
Breast cancer incidence, incidence trends, and survival rates as a function of age and extent of disease at diagnosis were obtained from 3 SEER registries that provide data spanning 1973-2009, 1992-2009, and 2000-2009. SEER defines localized as disease confined to the breast, regional to contiguous and adjacent organ spread (eg, lymph nodes, chest wall), and distant disease to remote metastases (bone, brain, lung, etc).
Breast cancer incidence trends in the United States.
In the United States, the incidence of breast cancer with distant involvement at diagnosis increased in 25- to 39-year-old women from 1.53 (95% CI, 1.01 to 2.21) per 100,000 in 1976 to 2.90 (95% CI, 2.31 to 3.59) per 100,000 in 2009. This is an absolute difference of 1.37 per 100,000, representing an average compounded increase of 2.07% per year (95% CI, 1.57% to 2.58%; P < .001) over the 34-year interval. No other age group or extent-of-disease subgroup of the same age range had a similar increase. For 25- to 39-year-olds, there was an increased incidence in distant disease among all races and ethnicities evaluated, especially non-Hispanic white and African American, and this occurred in both metropolitan and nonmetropolitan areas. Incidence for women with estrogen receptor-positive subtypes increased more than for women with estrogen receptor-negative subtypes. CONCLUSION AND RELEVANCE: Based on SEER data, there was a small but statistically significant increase in the incidence of breast cancer with distant involvement in the United States between 1976 and 2009 for women aged 25 to 39 years, without a corresponding increase in older women.
Factors captured in a geriatric assessment can predict morbidity and mortality in older adults, but are not routinely measured in cancer clinical trials. This study evaluated the implementation of a geriatric assessment tool in the cooperative group setting.
Patients age ≥ 65 with cancer, who enrolled on cooperative group cancer trials, were eligible to enroll on Cancer and Leukemia Group B (CALGB) 360401. They completed a geriatric assessment tool before initiation of protocol therapy, consisting of valid and reliable geriatric assessment measures which are primarily self-administered and require minimal resources and time by healthcare providers. The assessment measures functional status, comorbidity, cognitive function, psychological state, social support, and nutritional status. The protocol specified criteria for incorporation of the tool in future cooperative group trials was based on the time to completion and percent of patients who could complete their portion without assistance. Patient satisfaction with the tool was captured.
Of the 93 patients who enrolled in this study, five (5%) met criteria for cognitive impairment and three did not complete the cognitive screen, leaving 85 assessable patients (median age, 72 years). The median time to complete the geriatric assessment tool was 22 minutes, 87% of patients (n = 74) completed their portion without assistance, 92% (n = 78) were satisfied with the questionnaire length, 95% (n = 81) reported no difficult questions, and 96% (n = 82) reported no upsetting questions. One hundred percent of health care professionals completed their portion.
This brief, primarily self-administered geriatric assessment tool met the protocol specified criteria for inclusion in future cooperative group clinical trials.
Despite the importance of diversity of cancer trial participants with regard to race, ethnicity, age, and sex, there is little recent information about the representation of these groups in clinical trials.
To characterize the representation of racial and ethnic minorities, the elderly, and women in cancer trials sponsored by the National Cancer Institute.
Cross-sectional population-based analysis of all participants in therapeutic nonsurgical National Cancer Institute Clinical Trial Cooperative Group breast, colorectal, lung, and prostate cancer clinical trials in 2000 through 2002. In a separate analysis, the ethnic distribution of patients enrolled in 2000 through 2002 was compared with those enrolled in 1996 through 1998, using logistic regression models to estimate the relative risk ratio of enrollment for racial and ethnic minorities to that of white patients during these time periods.
Enrollment fraction, defined as the number of trial enrollees divided by the estimated US cancer cases in each race and age subgroup.
Cancer research participation varied significantly across racial/ethnic and age groups. Compared with a 1.8% enrollment fraction among white patients, lower enrollment fractions were noted in Hispanic (1.3%; odds ratio [OR] vs whites, 0.72; 95% confidence interval [CI], 0.68-0.77; P<.001) and black (1.3%; OR, 0.71; 95% CI, 0.68-0.74; P<.001) patients. There was a strong relationship between age and enrollment fraction, with trial participants 30 to 64 years of age representing 3.0% of incident cancer patients in that age group, in comparison to 1.3% of 65- to 74-year-old patients and 0.5% of patients 75 years of age and older. This inverse relationship between age and trial enrollment fraction was consistent across racial and ethnic groups. Although the total number of trial participants increased during our study period, the representation of racial and ethnic minorities decreased. In comparison to whites, after adjusting for age, cancer type, and sex, patients enrolled in 2000 through 2002 were 24% less likely to be black (adjusted relative risk ratio, 0.76; 95% CI, 0.65-0.89; P<.001). Men were more likely than women to enroll in colorectal cancer trials (enrollment fractions: 2.1% vs 1.6%, respectively; OR, 1.30; 95% CI, 1.24-1.35; P<.001) and lung cancer trials (enrollment fractions: 0.9% vs 0.7%, respectively; OR, 1.23; 95% CI, 1.16-1.31; P<.001).
Enrollment in cancer trials is low for all patient groups. Racial and ethnic minorities, women, and the elderly were less likely to enroll in cooperative group cancer trials than were whites, men, and younger patients, respectively. The proportion of trial participants who are black has declined in recent years.
Although 61% of new cases of cancer occur among the elderly, recent studies indicate that the elderly comprise only 25% of participants in cancer clinical trials. Further investigation into the reasons for low elderly participation is warranted. Our objective was to evaluate the participation of the elderly in clinical trials sponsored by the National Cancer Institute (NCI) and assess the impact of protocol exclusion criteria on elderly participation.
We conducted a retrospective analysis using NCI data, analyzing patient and trial characteristics for 59,300 patients enrolled onto 495 NCI-sponsored, cooperative group trials, active from 1997 through 2000. Our main outcome measure was the proportion of elderly patients enrolled onto cancer clinical trials compared with the proportion of incident cancer patients who are elderly.
Overall, 32% of participants in phase II and III clinical trials were elderly, compared with 61% of patients with incident cancers in the United States who are elderly. The degree of underrepresentation was more pronounced in trials for early-stage cancers than in trials for late-stage cancers (P <.001). Furthermore, protocol exclusion criteria on the basis of organ-system abnormalities and functional status limitations were associated with lower elderly participation. We estimate that if protocol exclusions were relaxed, elderly participation in cancer trials would be 60%.
The elderly are underrepresented in cancer clinical trials relative to their disease burden. Older patients are more likely to have medical histories that make them ineligible for clinical trials because of protocol exclusions. Insurance coverage for clinical trials is one step toward improvement of elderly access to clinical trials. Without a change in study design or requirements, this step may not be sufficient.
Enrolling participants onto clinical trials of cancer presents an important challenge. We aimed to identify the concerns of patients with cancer about, and the barriers to, participation in clinical trials.
We did a systematic review to assess studies of barriers to participation in experimental trials and randomised trials for validity and content. We estimated the frequency with which patients identified particular issues by pooling across studies that presented data for barriers to participation in clinical trials as proportions.
We analysed 12 qualitative studies (n=722) and 21 quantitative studies (n=5452). Two qualitative studies inquired of patients who were currently enrolled onto clinical trials, and ten inquired of patients who were eligible for enrolment onto various clinical trials. Barriers to participation in clinical trials were protocol-related, patient-related, or physician-related. The most common reasons cited as barriers included: concerns with the trial setting; a dislike of randomisation; general discomfort with the research process; complexity and stringency of the protocol; presence of a placebo or no-treatment group; potential side-effects; being unaware of trial opportunities; the idea that clinical trials are not appropriate for serious diseases; fear that trial involvement would have a negative effect on the relationship with their physician; and their physician's attitudes towards the trial. Meta-analysis confirmed the findings of our systematic review.
The identification of such barriers to the participation in clinical trials should help trialists to develop strategies that will keep to a maximum participation and cooperation in cancer trials, while informing and protecting prospective participants adequately.
Purpose:
Less than 10% of patients enrolled in clinical trials are minorities. The patient navigation model has been used to improve access to medical care but has not been evaluated as a tool to increase the participation of minorities in clinical trials. The Increasing Minority Participation in Clinical Trials project used patient navigators (PNs) to enhance the recruitment of African Americans for and their retention in therapeutic cancer clinical trials in a National Cancer Institute-designated comprehensive cancer center.
Methods:
Lay individuals were hired and trained to serve as PNs for clinical trials. African American patients potentially eligible for clinical trials were identified through chart review or referrals by clinic nurses, physicians, and social workers. PNs provided two levels of services: education about clinical trials and tailored support for patients who enrolled in clinical trials.
Results:
Between 2007 and 2014, 424 African American patients with cancer were referred to the Increasing Minority Participation in Clinical Trials project. Of those eligible for a clinical trial (N = 378), 304 (80.4%) enrolled in a trial and 272 (72%) consented to receive patient navigation support. Of those receiving patient navigation support, 74.5% completed the trial, compared with 37.5% of those not receiving patient navigation support. The difference in retention rates between the two groups was statistically significant (P < .001). Participation of African Americans in therapeutic cancer clinical trials increased from 9% to 16%.
Conclusion:
Patient navigation for clinical trials successfully retained African Americans in therapeutic trials compared with non-patient navigation trial participation. The model holds promise as a strategy to reduce disparities in cancer clinical trial participation. Future studies should evaluate it with racial/ethnic minorities across cancer centers.
The identification of changes in the recent trend is an important issue in the analysis of cancer mortality and incidence data. We apply a joinpoint regression model to describe such continuous changes and use the grid-search method to fit the regression function with unknown joinpoints assuming constant variance and uncorrelated errors. We find the number of significant joinpoints by performing several permutation tests, each of which has a correct significance level asymptotically. Each p-value is found using Monte Carlo methods, and the overall asymptotic significance level is maintained through a Bonferroni correction. These tests are extended to the situation with non-constant variance to handle rates with Poisson variation and possibly autocorrelated errors. The performance of these tests are studied via simulations and the tests are applied to U.S. prostate cancer incidence and mortality rates.
Discordant trends in the incidence of metastatic breast and prostate cancer since the widespread implementation of early-detection efforts may reflect distinct disease dynamics or may result from the different screening strategies used.
Racial and ethnic diversity has historically been difficult to achieve in National Cancer Institute-sponsored clinical trials, even while as many as 80% of those trials have faced difficulty in meeting overall recruitment targets. In an attempt to address these issues, NRG Oncology recently convened a comprehensive workshop titled "Clinical Trials Enrollment: Challenges and Opportunities." Discussants at the workshop included representatives of the three legacy groups of the NRG (ie, Gynecologic Oncology Group, National Surgical Adjuvant Breast and Bowel Program, and Radiation Therapy Oncology Group), a minority-based community clinical oncology program, a large integrated health care system, the leadership of the National Cancer Institute, and a large patient advocacy group. This article summarizes the concepts discussed at the workshop, which included: needs assessments, infrastructural support, training of investigators and research staff, specific clinical trial recruitment strategies (both system and community based), and development and mentoring of young investigators. Many new, more specific tactics, including use of diverse cancer care settings, direct-to-consumer communication, and the need for centralized information technology such as the use of software to match trials to special populations, are presented. It was concluded that new, innovative trial designs and the realities of limited funding would require the adoption of effective and efficient recruiting strategies, specialized training, and stakeholder engagement. US clinical research programs must generate and embrace new ideas and pilot test novel recruitment strategies if they are to maintain their historic role as world leaders in cancer care innovation and delivery.
Cancer constitutes an enormous burden on society in more and less economically developed countries alike. The occurrence of cancer is increasing because of the growth and aging of the population, as well as an increasing prevalence of established risk factors such as smoking, overweight, physical inactivity, and changing reproductive patterns associated with urbanization and economic development. Based on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide. Over the years, the burden has shifted to less developed countries, which currently account for about 57% of cases and 65% of cancer deaths worldwide. Lung cancer is the leading cause of cancer death among males in both more and less developed countries, and has surpassed breast cancer as the leading cause of cancer death among females in more developed countries; breast cancer remains the leading cause of cancer death among females in less developed countries. Other leading causes of cancer death in more developed countries include colorectal cancer among males and females and prostate cancer among males. In less developed countries, liver and stomach cancer among males and cervical cancer among females are also leading causes of cancer death. Although incidence rates for all cancers combined are nearly twice as high in more developed than in less developed countries in both males and females, mortality rates are only 8% to 15% higher in more developed countries. This disparity reflects regional differences in the mix of cancers, which is affected by risk factors and detection practices, and/or the availability of treatment. Risk factors associated with the leading causes of cancer death include tobacco use (lung, colorectal, stomach, and liver cancer), overweight/obesity and physical inactivity (breast and colorectal cancer), and infection (liver, stomach, and cervical cancer). A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests. CA Cancer J Clin 2015;65: 87-108. (c) 2015 American Cancer Society.
To enhance nurses' awareness and competencies in practice and research by reporting the common barriers to participation of minorities in cancer clinical trials and discussing facilitators and useful strategies for recruitment. Several databases were searched for articles published in peer reviewed journals. Some of the barriers to minorities' participation in clinical trials were identified within the cultural social-context of cancer patients. The involvement of community networking was suggested as the most effective strategy for the recruitment of minorities in cancer clinical trials. Using culturally sensitive approaches to enhance ethnic minorities' participation is important for advancing cancer care and eliminating health disparities. Awareness of barriers and potential facilitators to the enrollment of ethnic minority cancer patients may contribute to enhancing nurses' competencies of recruiting ethnic minorities in nursing research, playing efficient roles in cancer clinical trials team, and providing culturally competent quality care.
Background
Underrepresentation of racial and ethnic minorities in clinical trials remains a reality while they have disproportionately higher rates of health disparities.
Objective
The purpose of this study was to identify successful community-engaged interventions that included health care providers as a key strategy in addressing barriers to clinical trial enrollment of underrepresented patients.
Design
A systematic review of the literature on interventions addressing enrollment barriers to clinical trials for racial and ethnic minorities was performed in Ovid MEDLINE, EBSCO Megafile, and EBSCO CINAHL. The systematic review identified 360 studies, and 20 were selected using the inclusion criteria. An iterative process extracted information from the eligible studies.
Results
The 20 selected studies were analyzed and then grouped by first author, nature of the clinical research initiative, priority populations, key strategies, and study outcomes. Nine of the studies addressed cancer clinical trials and 11 related to chronic medical conditions, including diabetes, hypertension management, and chronic kidney disease. The key strategies employed were categorized according to their presumed impact on barriers incurred at distinct steps in study recruitment: clinical trial awareness, opportunity to participate, and acceptance of enrollment. The strategies were further categorized by whether they would address barriers associated with minority perceptions of the research process and barriers related to how studies were designed and implemented.
Conclusion
Multiple and flexible strategies targeting providers and participants at provider sites and within communities might be needed to enroll underrepresented populations into clinical trials.
Background:
Our purpose was to identify physicians' individual characteristics, attitudes, and organizational contextual factors associated with higher enrollment of patients in cancer clinical trials among physician participants in the National Cancer Institute's Community Clinical Oncology Program (CCOP). We hypothesized that physicians' individual characteristics, such as age, medical specialty, tenure, CCOP organizational factors (i.e. policies and procedures to encourage enrollment), and attitudes toward participating in CCOP would directly determine enrollment. We also hypothesized that physicians' characteristics and CCOP organizational factors would influence physicians' attitudes toward participating in CCOP, which in turn would predict enrollment.
Methods:
We evaluated enrollment in National Cancer Institute-sponsored cancer clinical trials in 2011 among 481 physician participants using Structural Equation Modeling. The data sources include CCOP Annual Progress Reports, two surveys of CCOP administrators and physician participants, and the American Medical Association Masterfile.
Results:
Physicians with more positive attitudes toward participating in CCOP enrolled more patients than physicians with less positive attitudes. In addition, physicians who practiced in CCOPs that had more supportive policies and practices in place to encourage enrollment (i.e. offered trainings, provided support to screen and enroll patients, gave incentives to enroll patients, instituted minimum accrual expectations) also significantly enrolled more patients. Physician status as CCOP Principal Investigator had a positive direct effect on enrollment, while physician age and non-oncology medical specialty had negative direct effects on enrollment. Neither physicians' characteristics nor CCOP organizational factors indirectly influenced enrollment through an effect on physician attitudes.
Conclusion:
We examined whether individual physicians' characteristics and attitudes, as well as CCOP organizational factors, influenced patient enrollment in cancer clinical trials among CCOP physicians. Physician attitudes and CCOP organizational factors had positive direct effects, but not indirect effects, on physician enrollment of patients. Our results could be used to develop physician-directed strategies aimed at increasing involvement in clinical research. For example, administrators may want to ensure physicians have access to support staff to help screen and enroll patients or institute minimum accrual expectations. Our results also highlight the importance of recruiting physicians for volunteer clinical research programs whose attitudes and values align with programmatic goals. Given that physician involvement is a key determinant of patient enrollment in clinical trials, these interventions could expand the overall number of patients involved in cancer research. These strategies will be increasingly important as the CCOP network continues to evolve.
Patient navigation programs are emerging that aim to address disparities in clinical trial participation among medically underserved populations, including racial/ethnic minorities. However, there is a lack of consensus on the role of patient navigators within the clinical trial process as well as outcome measures to evaluate program effectiveness.
A review of the literature was conducted of PubMed, Medline, CINHAL, and other sources to identify qualitative and quantitative studies on patient navigation in clinical trials. The search yielded 212 studies, of which only 12 were eligible for this review.
The eligible studies reported on the development of programs for patient navigation in cancer clinical trials, including training and implementation among African Americans, American Indians, and Native Hawaiians. A low rate of clinical trial refusal (range, 4%-6%) was reported among patients enrolled in patient navigation programs. However, few studies reported on the efficacy of patient navigation in increasing clinical treatment trial enrollment.
Outcome measures are proposed to assist in developing and evaluating the efficacy and/or effectiveness of patient navigation programs that aim to increase participation in cancer clinical trials. Future research is needed to evaluate the efficacy of patient navigators in addressing barriers to clinical trial participation and increasing enrollment among medically underserved cancer patients. Cancer 2014;120(7 suppl):1122-30. © 2014 American Cancer Society.
The study of disparities in minority recruitment to cancer clinical trials has focused primarily on inquiries among minority populations. Yet very little is known about the perceptions of individuals actively involved in minority recruitment to clinical trials within cancer centers. Therefore, the authors assessed the perspectives of cancer center clinical and research personnel on barriers and facilitators to minority recruitment.
In total, 91 qualitative interviews were conducted at 5 US cancer centers among 4 stakeholder groups: cancer center leaders, principal investigators, research staff, and referring clinicians. All interviews were recorded and transcribed. Qualitative analyses of response data was focused on identifying prominent themes related to barriers and facilitators to minority recruitment.
The perspectives of the 4 stakeholder groups were largely overlapping with some variations based on their unique roles in minority recruitment. Four prominent themes were identified: 1) racial and ethnic minorities are influenced by varying degrees of skepticism related to trial participation, 2) potential minority participants often face multilevel barriers that preclude them from being offered an opportunity to participate in a clinical trial, 3) facilitators at both the institutional and participant level potentially encourage minority recruitment, and 4) variation between internal and external trial referral procedures may limit clinical trial opportunities for racial and ethnic minorities.
Multilevel approaches are needed to address barriers and optimize facilitators within cancer centers to enhance minority recruitment for cancer clinical trials. Cancer 2014;120(7 suppl):1097-105. © 2014 American Cancer Society.
The National Institutes of Health (NIH) Revitalization Act of 1993 mandated the appropriate inclusion of minorities in all NIH-funded research. Twenty years after this act, the proportion of minority patients enrolled in cancer clinical trials remains persistently low. Clinical trials are vehicles for the development and evaluation of therapeutic and preventive agents under scientifically rigorous conditions. Without representation in trials, it is projected that disparities in the cancer burden for minorities will increase.
For this review article, the authors counted the frequency with which minorities were the primary focus of National Cancer Institute-sponsored clinical trials, examined citations from the PubMed database focusing on the search terms "NIH Revitalization Act of 1993" and "enhancing minority accrual to cancer clinical trials," and supplemented the review with their expertise in NIH-funded research related to minority accrual in cancer clinical trials.
The reporting and analyses of data based on minorities in clinical trials remain inadequate. Less than 2% of the National Cancer Institute's clinical trials focus on any racial/minority population as their primary emphasis. The current review of the literature indicated that the percentage of authors who reported their study sample by race/ethnicity ranged from 1.5% to 58%, and only 20% of the randomized controlled studies published in a high-impact oncology journal reported analyzing results by race/ethnicity. Proportionately greater population increases in minorities, accompanied by their persistent and disproportionate cancer burden, reinforce the need for their greater representation in clinical trials.
Renewing the emphasis for minority participation in clinical trials is warranted. Policy changes are recommended. Cancer 2014;120(7 suppl):1091-6. © 2014 American Cancer Society.
Findings from the recently released report from the Institute of Medicine (IOM) Committee on Improving the Quality of Cancer Care: Addressing the Challenges of an Aging Population, titled Delivering High-Quality Cancer Care: Charting a Course for a System in Crisis,1,2 underscore that the United States has entered a new era in cancer care. The complexity of challenges that US society will confront in achieving the quality of care and outcomes individuals seek and deserve have been magnified because cancer is now an integral part of the aging phenomenon. As the earliest wave of baby boomers enters Medicare, cancer is diagnosed at a higher rate (53%), accounts for a higher percentage of survivors (59%), and results in more deaths among individuals 65 years and older (68%), compared with younger individuals.3,4 With 10 000 individuals reaching age 65 years each day, the incidence of cancer is expected to increase by 67% among this population from 2010 to 2030.5 Unquestionably, this major shift in demographics further complicates the crisis in cancer care. As members of the aforementioned IOM Committee, we highlight issues unique to the older adult population that will substantially affect the capacity to effectively implement the committee’s proposed roadmap.1
Racial and ethnic minorities, older adults, rural residents, and individuals of low socioeconomic status are underrepresented among participants in cancer-related trials. The authors conducted a systematic review to determine the barriers to participation of underrepresented populations in cancer-related trials. Their search included English-language publications that reported original data on the recruitment of underrepresented groups to cancer treatment or prevention trials between 1966 and December 2005 in multiple electronic databases. They also hand-searched titles in 34 journals from January 2003 to December 2005 and they examined reference lists for eligible articles. Titles and abstracts were reviewed to identify relevant studies. Data on barriers to participation were synthesized both qualitatively and based on statistically significant associations with trial enrollment. Of 5257 studies that were cited, 65 studies were eligible for inclusion in the current analysis, including 46 studies on recruitment into cancer therapeutic trials, 15 studies on recruitment into prevention trials, and 4 studies on recruitment into both prevention and treatment trials. Numerous factors were reported as barriers to participation in cancer-related trials. However, only 20 of the studies reported statistically significant associations between hypothesized barriers and enrollment. The available evidence had limitations in quality regarding representativeness, justification of study methods, the reliability and validity of data-collection methods, potential for bias, and data analysis. The results indicated that underrepresented populations face numerous barriers to participation in cancer-related trials. The current systematic review highlighting the literature on recruitment of underrepresented populations to cancer trials and may be used as the evidence base toward developing an agenda for etiologic and intervention research to reduce the disparities in participation in cancer-related trials. Cancer 2008. © 2007 American Cancer Society.
Studies have documented the underrepresentation of women and blacks in clinical trials, and their recruitment is now federally mandated. However, little is known about the level of participation of elderly patients. We determined the rates of enrollment of patients 65 years of age or older in trials of treatment for cancer.
We analyzed data on 16,396 patients consecutively enrolled in 164 Southwest Oncology Group treatment trials between 1993 and 1996 according to sex, race (black or white), and age under 65 years or 65 or older. These rates were compared with the corresponding rates in the general population of patients with cancer, derived from the 1990 U.S. Census and from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program for the period from 1992 through 1994. Fifteen types of cancer were included in the analysis.
The overall proportions of women and blacks enrolled in Southwest Oncology Group trials were similar to or the same as the estimated proportions in the U.S. population of patients with cancer (women, 41 percent and 43 percent; blacks, 10 percent and 10 percent, respectively). In contrast, patients 65 years of age or older were underrepresented overall (25 percent vs. 63 percent, P<0.001) and in trials involving all 15 types of cancer except lymphoma. The underrepresentation was particularly notable in trials of treatment for breast cancer (9 percent vs. 49 percent, P<0.001). The findings were similar when data on patients who were 70 years of age or older were analyzed, when 15 trials that excluded older patients were eliminated from the analysis, and when community-based enrollment was analyzed separately from enrollment at academic centers.
There is substantial underrepresentation of patients 65 years of age or older in studies of treatment for cancer. The reasons should be clarified, and policies adopted to correct this underrepresentation.
National health statistics indicate that blacks have lower survival rates from colorectal cancer than do whites. This disparity has been attributed to differences in stage at diagnosis and other disease features, extent and quality of treatment, and socioeconomic factors. We evaluated outcomes for blacks and whites with rectal cancer who participated in randomized clinical trials of the National Surgical Adjuvant Breast and Bowel Project (NSABP). The randomized trial setting enhances uniformity in disease stage and treatment plan among all participants.
The study included black (N = 104) or white (N = 1,070) patients from two serially conducted NSABP randomized trials for operable rectal cancer. Recurrence-free survival and survival were compared using statistical modeling to account for differences in patient and disease characteristics between the groups.
Blacks and whites had largely similar disease features at diagnosis. After adjustment for patient and tumor prognostic covariates, the black/white recurrence hazard ratio (HR) was 1.25 (95% confidence interval [CI], 0.94 to 1.66). The mortality HR was somewhat larger at 1.45 (95% CI = 1.09 to 1.93). Outcomes were improved for both groups in the more recent trial, which employed systemic adjuvant chemotherapy in all treatment arms.
Recurrence-free survival was modestly less favorable for blacks, whereas overall survival was more disparate. Outcomes between groups were more comparable than those noted in national health statistics surveys and other studies. Adequate treatment access and the identification of new prognostic factors that can identify patients at high risk of recurrence are needed to ensure optimal outcomes for rectal cancer patients of all racial/ethnic backgrounds.
Older patients are significantly underrepresented in cancer clinical trials. A literature review was undertaken to identify the barriers that impede the accrual of this vulnerable population onto clinical trials and to determine what specific strategies are needed to improve the representation of older patients in research studies.
A systematic literature search was undertaken using several different strategies to identify relevant articles.
Nine of 31 relevant papers from 159 citations were included. Age is a significant barrier to recruitment; only a quarter to one third of potentially eligible older patients are enrolled onto trials. Physicians' perceptions, protocol eligibility criteria with restrictions on comorbid conditions, and functional status to optimize treatment tolerability are the most important reasons resulting in the exclusion of older patients. Other barriers include the lack of social support and the need for extra time and resources to enroll these patients. Conversely, older patients do not view their age as an important reason for refusing trials.
Specific clinical trials confined to older patients should be conducted to evaluate tumor biology, treatment tolerability, and the effect of comorbid conditions. Protocol designs need to stratify for age and be less restrictive with respect to exclusions on functional status, comorbidity, and previous cancers, such that results are generalizable to older patients. Physician education to dispel unfounded perceptions, improved access to available clinical trials, and provision of personnel and resources to accommodate the unique requirements of an older population are possible solutions to remove the barriers of ageism.
Global cancer statistics
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Torre LA, Bray F, Siegel RL, et al: Global cancer
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16. Brooks SE, Muller CY, Robinson W, et al: Increasing minority enrollment onto clinical trials:
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School of Public Health, Li Ka Shing Faculty of Medicine
- Affiliations Herbert
- H Pang
- Perry Cheng
Affiliations
Herbert H. Pang and Perry Cheng, School of Public Health, Li Ka Shing Faculty of Medicine, Hong Kong, Special Administrative Region,
People's Republic of China;
Helen Diller Family Comprehensive Cancer Center
- Melisa L Wong
Melisa L. Wong, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San
Francisco;
Mandrekar No relationship to disclose
- J Sumithra
Sumithra J. Mandrekar
No relationship to disclose
Redman No relationship to disclose
- W Mary
Mary W. Redman
No relationship to disclose
Schilsky No relationship to disclose
- L Richard
Richard L. Schilsky
No relationship to disclose
Cohen No relationship to disclose
- J Harvey
Harvey J. Cohen
No relationship to disclose
ViewRay (Inst) Travel, Accommodations, Expenses: Mevion Medical Systems Alex A. Adjei No relationship to disclose David Gandara Consulting or Advisory Role: ARIAD Pharmaceuticals
- D Jeffrey
- Bradley Honoraria
Jeffrey D. Bradley
Honoraria: ViewRay
Consulting or Advisory Role: ViewRay (Inst), Varian Medical Systems
Research Funding: Mevion Medical Systems (Inst), ViewRay (Inst)
Travel, Accommodations, Expenses: Mevion Medical Systems
Alex A. Adjei
No relationship to disclose
David Gandara
Consulting or Advisory Role: ARIAD Pharmaceuticals, AstraZeneca,
Boehringer Ingelheim, Celgene, Clovis Oncology, Genentech, Guardant
Health, Eli Lilly, Merck, Mirati Therapeutics, Novartis, Pfizer
Research Funding: AstraZeneca/MedImmune (Inst), Bristol-Myers
Squibb (Inst), Clovis Oncology (Inst), Genentech (Inst), Johnson &
Johnson (Inst), Eli Lilly (Inst), Merck (Inst), Novartis (Inst)
Vokes Stock or Other Ownership: McKesson Consulting or Advisory Role
- E Everett
Everett E. Vokes
Stock or Other Ownership: McKesson
Consulting or Advisory Role: Eli Lilly