Kimberley S. Mak’s research while affiliated with University of Massachusetts Boston and other places

Introduction The development of immune-related adverse events (irAEs) has been associated with improved survival outcomes in non-small cell lung cancer (NSCLC). However, this association’s extent across race and ethnicity remains uncertain. We evaluated the association between the development of irAEs and treatment outcomes across racially diverse groups treated at a safety net hospital. Methods A retrospective chart review was performed to identify patients with advanced NSCLC treated between 2015 and 2020. The incidence of irAEs across racial subgroups was compared using logistic regression analysis. Cox regression analysis was performed to evaluate the association between the development of irAEs and treatment outcomes. Results We identified 138 NSCLC patients treated with immune checkpoint inhibitors (ICIs), of whom 50% identified as non-Hispanic Black (NHB). Incidence of irAEs was 28%, with no significant difference between NHB and other racial groups. However, females [OR 2.3, 95% CI, (1.1-4.8)] and patients with Medicaid or MassHealth insurance had a higher incidence of irAEs [OR 2.7 (1.2-5.7)]. Additionally, patients with irAEs had a lower risk of disease progression (multivariable HR 0.46, 95% CI, 0.23-0.92) compared to those without irAEs. The association between irAEs and improved progression free survival (PFS) in NHB patients was similar to the other racial group [median PFS 246 vs 181 days; HR 0.87 (0.58-1.29)]. Conclusion We demonstrated a similar incidence of irAEs in NHB patients with NSCLC as compared to other racial groups. Patients who developed irAEs experienced significantly improved survival outcomes. This association remained independent of race and ethnicity, underscoring the importance of providing unbiased treatment recommendations.

Purpose The optimal delivery schedule for stereotactic body radiation therapy (SBRT) in treating stage I non-small cell lung cancer (NSCLC) is unknown. This study used the National Cancer Database to examine daily versus every other day (QOD) SBRT scheduling, including trends over time and association with survival. Methods and Materials The National Cancer Database was used to retrospectively identify patients with stage I NSCLC treated with 3-, 4-, or 5-fraction of SBRT between 2004 and 2016. Survival analysis was performed using the Kaplan-Meier method and Cox regression modeling. Results Of 15,269 patients, 3927 (25.7%) received SBRT daily, and 11,342 (74.3%) received treatment QOD. The use of QOD treatment increased from 63.2% in 2007 to 78.3% in 2016, and 5-fraction SBRT increased from 3.7% in 2004 to 51.4% in 2016 (both P < .0001). QOD 5-fraction became the most prevalent scheduling from 2012 to 2016 (28.5% in 2012 to 41.6% in 2016). Factors significantly associated with daily SBRT scheduling included number of fractions, race, lower income, lower comorbidities, and treatment at academic/research programs (all P ≤ .01). Median survival for daily SBRT was 37.9 months versus 38.4 months for QOD (P = .4). On multivariable analysis, no difference was found in overall survival between daily versus QOD scheduling (adjusted hazard ratio [aHR], 0.99; 95% confidence interval [CI], 0.94-1.04; P = .55). Five-fraction SBRT was associated with worse survival versus 3 fractions (aHR, 1.09; 95% CI, 1.03-1.15; P = .002). With 3-fraction SBRT, QOD treatment was associated with improved survival versus daily treatment (aHR, 0.91; 95% CI, 0.84-0.98; P = .02). With 5-fraction SBRT, QOD treatment was associated with worse survival versus daily treatment (aHR, 1.11; 95% CI, 1.02-1.22; P = .02). Conclusions QOD SBRT schedules were more frequently used to treat stage I NSCLC than daily regimens by a factor of 3:1, and QOD 5-fraction SBRT became the most common dose schedule after 2012. Three-fraction QOD SBRT was associated with improved survival versus daily, whereas 5-fraction QOD SBRT was associated with worse survival versus daily.

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: The aim of this study was to determine if change in stage after neoadjuvant chemoradiation (CRT) was associated with improved survival in esophageal cancer using a national database. Methods: Using the National Cancer Database, patients with non-metastatic, resectable esophageal cancer who received neoadjuvant CRT and surgery were identified. Comparing clinical to the pathologic stage, change in stage was classified as pathologic complete response (pCR), downstaged, same-staged, or upstaged. Univariable and multivariable Cox regression models were used to identify factors associated with survival. Results: A total of 7745 patients were identified. The median overall survival (OS) was 34.9 months. Median OS was 60.3 months if pCR, 39.1 months if downstaged, 28.3 months if same-staged, and 23.4 months if upstaged (p < 0.0001). On multivariable analysis, pCR was associated with improved OS compared to the other groups (downstaged: hazard ratio [HR]: 1.32 [95% confidence interval [CI]: 1.18-1.46]; same-staged: HR: 1.89 [95% CI: 1.68-2.13]; upstaged: HR: 2.54 [95% CI: 2.25-2.86]; all p < 0.0001). Conclusions: In this large database study, change in stage after neoadjuvant CRT was strongly associated with survival for patients with non-metastatic, resectable esophageal cancer. There was a significant stepwise decline in survival, in descending order of pCR, downstaged tumor, same-staged tumor, and upstaged tumor.

e21220 Background: The development of immune-related adverse events (irAEs) in patients treated with immune checkpoint inhibitors (ICIs) has been associated with improved clinical outcomes in advanced non-small cell lung cancer (NSCLC). However, how this association extends across race and ethnicity remains uncertain. In this study, we evaluated the association between the development of irAEs and treatment outcomes across different racial and ethnic groups treated at a single institution. Methods: We performed a retrospective chart review to identify irAEs and treatment outcomes in patients with advanced NSCLC who had received treatment with ICIs at our institution between 2015-2020. The incidence of irAEs across racial subgroups was compared using logistic regression analysis. Cox regression analysis was carried out to evaluate the associations between the development of irAEs and treatment outcomes [Overall Survival (OS) and Progression Free Survival (PFS)] in these subgroups. Results: We identified a total of 138 NSCLC patients who received treatment with ICIs, of whom 50% (69) identified as non-Hispanic Black (NHB) and 50% (69) as others, including 34% (47) as non-Hispanic White. The overall incidence of irAEs in the cohort was 28%, with no significant difference between NHB and other racial groups (29% vs. 27.5%). However, females [OR 2.3 (1.1-4.8)] and patients who did not have Medicare or private insurance (i.e had Medicaid or MassHealth) were found to have a higher incidence of irAEs [OR 2.7 (1.2-5.7)]. With a median follow-up time of 363 days, the proportion of patients who were progression-free was greater in patients who had experienced irAEs than in those who did not experience irAEs [HR for time to progression 0.46 (0.23 – 0.92)]. The association between irAEs and improved PFS in NHB patients was similar to the overall population [median PFS 246 vs. 181; HR 0.87 (0.58-1.29)]. Higher ECOG status, higher Charlson Comorbidity Index and receiving ICIs as 2 nd or subsequent line therapy were independently associated with worse PFS. Conclusions: Our single-institution study demonstrated a similar incidence of irAEs in patients with NSCLC across different racial and ethnic groups. As in prior studies, patients undergoing treatment with ICIs and experiencing irAEs had significantly better outcomes. We found that the association between the development of irAEs and improved treatment outcomes was independent of race and ethnicity, supporting the importance of making unbiased treatment recommendations without regard to these factors. [Table: see text]

Purpose We evaluated he effects of molecular guided-targeted therapy for intractable cancer. Also, the epidemiology of druggable gene alterations in Chinese population was investigated. Materials and methods The Long March Pathway (ClinicalTrials.gov identifier: NCT03239015) is a non-randomized, open-label, phase II trial consisting of several basket studies examining the molecular profiles of intractable cancers in the Chinese population. The trial aimed to 1) evaluate the efficacy of targeted therapy for intractable cancer and 2) identify the molecular epidemiology of the tier II gene alterations among Chinese pan-cancer patients. Results In the first stage, molecular profiles of 520 intractable pan-cancer patients were identified, and 115 patients were identified to have tier II gene alterations. Then, 27 of these 115 patients received targeted therapy based on molecular profiles. The overall response rate (ORR) was 29.6% (8/27), and the disease control rate (DCR) was 44.4% (12/27). The median duration of response (DOR) was 4.80 months (95% CI, 3.33−27.2), and median progression-free survival (PFS) was 4.67 months (95% CI, 2.33−9.50). In the second stage, molecular epidemiology of 17,841 Chinese pan-cancer patients demonstrated that the frequency of tier II gene alterations across cancer types is 17.7%. Bladder cancer had the most tier-II alterations (26.1%), followed by breast cancer (22.4%), and non-small cell lung cancer (NSCLC; 20.2%). Conclusion The Long March Pathway trial demonstrated a significant clinical benefit for intractable cancer from molecular-guided targeted therapy in the Chinese population. The frequency of tier II gene alterations across cancer types supports the feasibility of molecular-guided targeted therapy under basket trials.