[Show abstract][Hide abstract] ABSTRACT: Among the estimated 230,000 men diagnosed with prostate cancer in the US each year there has been a rise in the number of radical prostatectomies (RP). There is some debate over the value of immediate adjuvant therapy following RP in men with high-risk pathological features versus delayed salvage radiation therapy when signs of disease progression are observed. Thus, it would be potentially useful to inform post-RP management strategies by more clearly identifying those patients at higher risk of progression and death from prostate cancer. A 22 gene-expression assay, Decipher® (GenomeDx Biosciences), has been developed in men treated with radical prostatectomy to predict the five-year risk of metastatic prostate cancer. Published and unpublished literature was evaluated to determine the analytic validity, clinical validity and clinical utility of Decipher. Limited information is available on the analytic validity of Decipher. In both discovery and validation studies, Decipher was shown to have good performance in discriminating men with metastasis from men without metastasis five years after surgery (AUC 0.75 to 0.90). In terms of clinical utility, no evidence was found reporting improved outcomes (lower prostate cancer specific mortality and treatment related adverse effects) from using this test to guide post-operative treatment. Four studies provided weak indirect evidence of clinical utility in which 31% to 43% of post-operative treatment recommendations were changed in men with high-risk prostate cancer based on test results, with 27% to 52% of treatment recommendations changing from any treatment to no treatment.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Some medical treatment for metastatic colorectal cancer (CRC) may have marginal survival benefit, but cause toxicities. The purpose of this study is to determine metastatic CRC patients' tradeoffs in making a decision to undergo new medical treatment.
We conducted a survey of patients with a diagnosis of advanced CRC who were currently receiving or completed one chemotherapy regimen. First, patients were asked to rate the importance of 15 medical treatment-related adverse events that may arise as a consequence of chemotherapy or biological therapy in their treatment decision-making. Then, the patient identified his or her top five most important events and solicited preferences in hypothetical metastatic CRC treatment vignettes using the standard gamble technique.
A total of 107 patients responded to the survey. From the list of medical treatment-related adverse events, patients identified clinically serious ones such as stroke, heart attack, and gastrointestinal perforation as the most important in their medical treatment decision-making, yet placed lower willingness to tolerate symptom-related events such as pain, fatigue, and depression. Generally, patients who were older, stage III versus IV and who had prior radiotherapy, lower educational attainment, and lower household income (all p <0.05) were less willing to tolerate any medical treatment-related adverse events after adjusting for other demographic and clinical characteristics.
Variations in patients' willingness to tolerate different treatment-related adverse events underscore the need for improved communications between physicians and patients about the risks and benefits of their medical treatment, which helps make a more personalized decision for metastatic CRC treatment.
No preview · Article · Nov 2015 · Journal of Cancer Research and Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: Background: A number of practice guidelines incorporate the use of gene expression profiling (GEP) tests for early-stage, hormone receptor-positive, HER2-negative breast tumors. Few studies describe factors associated with GEP testing in US oncology practice. We assessed the relationship between clinical, demographic, and group-level socioeconomic variables and test use in women younger than 65 years. Patients and Methods: Data from 5 state cancer registries were linked with insurance claims data and GEP test results. We assessed rates of testing and variables associated with test use in an incident cohort of 9,444 commercially insured women younger than 65 years, newly diagnosed with stage I or II hormone receptor-positive breast cancer from 2006 through 2012. Results: Rates of testing for women with N0 disease increased from 20.4% in 2006 to 35.2% in 2011. Variables associated with higher rates of testing, beyond clinical factors such as nodal status (P<.001), included being diagnosed from 2008 through 2012 versus 2006 through 2007 (adjusted odds ratio [OR], 1.67; 95% CI, 1.47-1.90), having preexisting comorbidities (adjusted OR, 1.35; 95% CI, 1.14-1.59), and higher out-of-pocket pharmacy costs (adjusted OR, 1.66; 95% CI, 1.40-1.97). Women younger than 50 years were more likely to be tested if they had stage I versus stage II disease (P<.0001). Conclusions: In an insured population of women younger than 65 years, GEP testing increased after its inclusion in clinical practice guidelines and mounting evidence. Additional research is needed to better understand oncologists' decision not to order GEP testing for their patients who are otherwise eligible.
No preview · Article · Oct 2015 · Journal of the National Comprehensive Cancer Network: JNCCN
[Show abstract][Hide abstract] ABSTRACT: To evaluate the validity of the Patient-Reported Outcomes Measurement Information System (PROMIS) physical function measures in a diverse, population-based cancer sample.
Cancer patients 6-13 months post-diagnosis (n = 4840) were recruited for the Measuring Your Health study. Participants were diagnosed between 2010 and 2013 with non-Hodgkin lymphoma or cancers of the colorectum, lung, breast, uterus, cervix, or prostate. Four PROMIS physical function short forms (4a, 6b, 10a, and 16) were evaluated for validity and reliability across age and race-ethnicity groups. Covariates included gender, marital status, education level, cancer site and stage, comorbidities, and functional status.
PROMIS physical function short forms showed high internal consistency (Cronbach's α = 0.92-0.96), convergent validity (fatigue, pain interference, FACT physical well-being all r ≥ 0.68), and discriminant validity (unrelated domains all r ≤ 0.3) across survey short forms, age, and race-ethnicity. Known-group differences by demographic, clinical, and functional characteristics performed as hypothesized. Ceiling effects for higher-functioning individuals were identified on most forms.
This study provides strong evidence that PROMIS physical function measures are valid and reliable in multiple race-ethnicity and age groups. Researchers selecting specific PROMIS short forms should consider the degree of functional disability in their patient population to ensure that length and content are tailored to limit response burden.
No preview · Article · May 2015 · Quality of Life Research
[Show abstract][Hide abstract] ABSTRACT: In several developed countries intermittent androgen deprivation therapy has been accepted over continuous androgen deprivation therapy for advanced prostate cancer management. To our knowledge its adoption and predictors of use in American urology practice remain unknown.
No preview · Article · Apr 2015 · Urology Practice
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND Guidelines recommend against treating localized prostate cancer (PCa) in men with a greater than 10-year life expectancy. However, physicians have difficulty accurately estimating life expectancy. OBJECTIVE We used data from a population-based observational study to develop a nomogram to estimate long-term other-cause mortality based on self-reported health status (SRHS), race/ethnicity, and age at diagnosis. DESIGN This was an observational study. SUBJECTS Men diagnosed with localized PCa from October 1994 through October 1995 participated in the study. MAIN MEASURES Initial measures obtained 6 months after diagnosis included sociodemographic and tumor characteristics, treatment, and a single item on the SRHS, with response options ranging from excellent to poor. We used Surveillance, Epidemiology, and End-Results program data to determine date and cause of death through December 2010. We estimated other-cause mortality with proportional hazards survival analyses, accounting for competing risks. KEY RESULTS We evaluated 2,695 men, of whom 74 % underwent aggressive therapy (surgery or radiotherapy). At the initial survey, 18 % reported excellent (E), 36 % very good (VG), 31 % good (G), and 15 % fair/poor (F/P) health. Healthier men were younger, and more likely to be white, better educated, and to undergo surgery. At follow-up, 44 % of the cohort had died; 78 % of deaths were from causes other than PCa. SRHS predicted other-cause mortality; for men reporting E, VG, G, F/P health, the cumulative incidences of other-cause mortality were 20 %, 29 %, 40 %, and 53 %, respectively, p CONCLUSIONS Responses to a one-item SRHS measure were strongly associated with other-cause mortality 15 years after PCa diagnosis. Men reporting fair/poor health had substantial risks for other-cause mortality, suggesting limited benefit for undergoing aggressive treatment. SRHS can be considered in supporting informed decision-making about PCa treatment.
No preview · Article · Feb 2015 · Journal of General Internal Medicine
[Show abstract][Hide abstract] ABSTRACT: Background
To examine factors associated with the use of radiation therapy (RT) at the end of life in patients with breast, prostate, or colorectal cancer.Methods
Using data from the Surveillance, Epidemiology, and End Results (SEER) ¿ Medicare database, patients were over age 65 and diagnosed between January 1, 2004 and December 31, 2011 with any stage of cancer when the cause of death, as defined by SEER, was cancer; or with stage 4 cancer, who died of any cause. We employed multiple logistic regression models to identify patient and health systems factors associated with palliative radiation use.Results50% of patients received RT in the last 6 months of life. RT was used less frequently in older patients and in non-Hispanic white patients. Similar patterns were observed in the last 14 days of life. Chemotherapy use in the last 6 months of life was strongly correlated with receiving RT in the last 6 months (OR 2.73, 95%? CI: 2.59-2.88) and last 14 days of life (OR 1.55, 95% CI: 1.40-1.66). Patients receiving RT accrued more emergency department visits, radiographic exams and physician visits (all comparisons p¿<¿0.0001).Conclusions
Among patients with breast, colorectal, and prostate cancer, palliative RT use was common. End-of-life RT correlated with end-of-life chemotherapy use, including in the last 14 days of life, when treatment may cause increased treatment burden without improved quality of life. Research is needed optimize the role and timing of RT in palliative care.
Full-text · Article · Jan 2015 · Radiation Oncology
[Show abstract][Hide abstract] ABSTRACT: Background:
There has been little improvement in the survival of adolescent and young adult (AYA) cancer patients aged 15 to 39 years relative to other age groups, raising the question of whether such patients receive appropriate initial treatment.
We examined receipt of initial cancer treatment for a population-based sample of 504 AYAs diagnosed in 2007-2008 with acute lymphoblastic leukemia (ALL), Hodgkin's or non-Hodgkin's lymphoma, germ cell cancer, or sarcoma. Registry data, patient surveys, and detailed medical record reviews were used to evaluate the association of patient demographic, socioeconomic, and health care setting characteristics with receipt of appropriate initial treatment, which was defined by clinical specialists in AYA oncology based on adult guidelines and published literature available before 2009 and analyzed with multivariable logistic regression. All statistical tests were two-sided.
Approximately 75% of AYA cancer patients in our sample received appropriate treatment, 68% after excluding stage I male germ cell patients who all received appropriate treatment. After this exclusion, appropriate treatment ranged from 79% of sarcoma patients to 56% of ALL patients. Cancer type (P < .01) and clinical trial participation (P = .04) were statistically significantly associated with appropriate treatment in multivariable analyses. Patients enrolled in clinical trials were more likely to receive appropriate therapy relative to those not enrolled (78% vs 67%, adjusted odds ratio = 2.6, 95% confidence interval = 1.1 to 6.4).
Except for those with early stage male germ cell tumors, approximately 30% (or 3 in 10) AYA cancer patients did not receive appropriate therapy. Further investigation is required to understand the reasons for this potential shortfall in care delivery.
Preview · Article · Nov 2014 · JNCI Journal of the National Cancer Institute
[Show abstract][Hide abstract] ABSTRACT: Purpose:
The Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) decreased fee-for-service (FFS) payments for outpatient chemotherapy. We assessed how this policy affected chemotherapy in FFS settings versus in integrated health networks (IHNs).
Patients and methods:
We examined 5,831 chemotherapy regimens for 3,613 patients from 2003 to 2006 with colorectal cancer (CRC) or lung cancers in the Cancer Care Outcomes Research Surveillance Consortium. Patients were from four geographically defined regions, seven large health maintenance organizations, and 15 Veterans Affairs Medical Centers. The outcome of interest was receipt of chemotherapy that included at least one drug for which reimbursement declined after the MMA.
The odds of receiving an MMA-affected drug were lower in the post-MMA era: the odds ratio (OR) was 0.73 (95% CI, 0.59 to 0.89). Important differences across cancers were detected: for CRC, the OR was 0.65 (95% CI, 0.46 to 0.92); for non-small-cell lung cancer (NSCLC), the OR was 1.60 (95% CI, 1.09 to 2.35); and for small-cell lung cancer, the OR was 0.63 (95% CI, 0.34 to 1.16). After the MMA, FFS patients were less likely to receive MMA-affected drugs: OR, 0.73 (95% CI, 0.59 to 0.89). No pre- versus post-MMA difference in the use of MMA-affected drugs was detected among IHN patients: OR, 1.01 (95% CI, 0.66 to 1.56). Patients with CRC were less likely to receive an MMA-affected drug in both FFS and IHN settings in the post- versus pre-MMA era, whereas patients with NSCLC were the opposite: OR, 1.60 (95% CI, 1.09 to 2.35) for FFS and 6.33 (95% CI, 2.09 to 19.11) for IHNs post- versus pre-MMA.
Changes in reimbursement after the passage of MMA appear to have had less of an impact on prescribing patterns in FFS settings than the introduction of new drugs and clinical evidence as well as other factors driving adoption of new practice patterns.
No preview · Article · Sep 2014 · Journal of Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: Primary androgen-deprivation therapy (PADT) is often used to treat clinically localized prostate cancer, but its effects on cause-specific and overall mortality have not been established. Given the widespread use of PADT and the potential risks of serious adverse effects, accurate mortality data are needed to inform treatment decisions.
We conducted a retrospective cohort study using comprehensive utilization and cancer registry data from three integrated health plans. All men were newly diagnosed with clinically localized prostate cancer. Men who were diagnosed between 1995 and 2008, were not treated with curative intent therapy, and received follow-up through December 2010 were included in the study (n = 15,170). We examined all-cause and prostate cancer-specific mortality as our main outcomes. We used Cox proportional hazards models with and without propensity score analysis.
Overall, PADT was associated with neither a risk of all-cause mortality (hazard ratio [HR], 1.04; 95% CI, 0.97 to 1.11) nor prostate-cancer-specific mortality (HR, 1.03; 95% CI, 0.89 to 1.19) after adjusting for all sociodemographic and clinical characteristics. PADT was associated with decreased risk of all-cause mortality but not prostate-cancer-specific mortality. PADT was associated with decreased risk of all-cause mortality only among the subgroup of men with a high risk of cancer progression (HR, 0.88; 95% CI, 0.78 to 0.97).
We found no mortality benefit from PADT compared with no PADT for most men with clinically localized prostate cancer who did not receive curative intent therapy. Men with higher-risk disease may derive a small clinical benefit from PADT. Our study provides the best available contemporary evidence on the lack of survival benefit from PADT for most men with clinically localized prostate cancer.
Preview · Article · Mar 2014 · Journal of Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: Stereotactic body radiation therapy (SBRT) is a technically demanding prostate cancer treatment that may be less expensive than intensity-modulated radiation therapy (IMRT). Because SBRT may deliver a greater biologic dose of radiation than IMRT, toxicity could be increased. Studies comparing treatment cost to the Medicare program and toxicity are needed.
We performed a retrospective study by using a national sample of Medicare beneficiaries age ≥ 66 years who received SBRT or IMRT as primary treatment for prostate cancer from 2008 to 2011. Each SBRT patient was matched to two IMRT patients with similar follow-up (6, 12, or 24 months). We calculated the cost of radiation therapy treatment to the Medicare program and toxicity as measured by Medicare claims; we used a random effects model to compare genitourinary (GU), GI, and other toxicity between matched patients.
The study sample consisted of 1,335 SBRT patients matched to 2,670 IMRT patients. The mean treatment cost was $13,645 for SBRT versus $21,023 for IMRT. In the 6 months after treatment initiation, 15.6% of SBRT versus 12.6% of IMRT patients experienced GU toxicity (odds ratio [OR], 1.29; 95% CI, 1.05 to 1.53; P = .009). At 24 months after treatment initiation, 43.9% of SBRT versus 36.3% of IMRT patients had GU toxicity (OR, 1.38; 95% CI, 1.12 to 1.63; P = .001). The increase in GU toxicity was due to claims indicative of urethritis, urinary incontinence, and/or obstruction.
Although SBRT was associated with lower treatment costs, there appears to be a greater rate of GU toxicity for patients undergoing SBRT compared with IMRT, and prospective correlation with randomized trials is needed.
Preview · Article · Mar 2014 · Journal of Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: Randomized controlled trials have reported a 4–5 times increased risk of heart failure (HF) in breast cancer patients receiving trastuzumab (Herceptin®
) compared to patients who do not receive trastuzumab. However, data regarding the cardiac effects of trastuzumab on elderly patients treated in general practice remain very limited. Using the US surveillance, epidemiology, and end results (SEER)-Medicare database, we conducted a retrospective cohort study on the cardiac effects of trastuzumab use in all incident breast cancer patients diagnosed from 1998 to 2007 who were 66 years and older, had no prior recent claims for cardiomyopathy (CM) or HF, and were followed through 2009. We defined our outcome as the first CM/HF event after diagnosis. We performed Cox-proportional hazard models with propensity score adjustment to estimate CM/HF risk associated with trastuzumab use. A total of 6,829 out of 68,536 breast cancer patients (median age: 75) had an incident CM/HF event. Patients who received trastuzumab tended to be younger, non-white, diagnosed more recently, and had a stage IV diagnosis. Trastuzumab use was associated with an increased risk of CM/HF (HR = 2.08, 95 % CI 1.77–2.44, p < 0.001). The trastuzumab-associated CM/HF risk was stronger in patients who were younger (HR = 2.52 for 66–75 years and HR = 1.44 for 76 years and older, p < 0.001) and diagnosed in recent years (HR = 2.58 for 2006–2007 vs. 1.86 for 1998–2005, p = 0.01). The twofold risk of CM/HF associated with trastuzumab remained regardless of patients’ diagnosis stage, presence of hypertension, cardiovascular comorbidities, or receipt of anthracyclines, taxanes, or radiation. Trastuzumab may double CM/HF risk among elderly breast cancer patients. Our findings reinforce the need to prevent and manage cardiac risk among elderly breast cancer patients receiving trastuzumab.
No preview · Article · Jan 2014 · Breast Cancer Research and Treatment