Background: The 21-gene recurrence score (RS) assay is retrospectively validated for assessing prognosis and benefit from chemotherapy in hormone receptor–positive, early-stage breast cancer (EBC) with low RS. We hypothesized that oncologists have already incorporated the RS assay for decision-making in higher-risk, node-positive disease, despite the lack of prospective data and contrary to NCCN Guideline recommendations. This study provides the first analysis of trends and differences in RS use and therapeutic implications in a population-based data set of patients with node-positive EBC. It also assesses the impact of the RxPONDER trial on clinicians' chemotherapy recommendations. Methods: Node-positive EBC cases diagnosed during 2010 through 2012 and included in the National Cancer Data Base were used. Multivariate logistic regression was used to estimate test use and impact on chemotherapy recommendations. Results: The RS assay was ordered for 16.5% of the 80,405 identified patients. Of all variables, the RS assay had the strongest association with chemotherapy recommendation, with adjusted odds ratios (AORs) of 19 for scores >30. Odds of chemotherapy recommendation were significantly lower for the group who received the test (AOR, 0.21; 95% CI, 0.20–0.22). When divided based on the cutoff point of 25 adopted by the RxPONDER trial, those with an RS of 18 to 25 had significantly lower odds of chemotherapy recommendation compared with those with an RS of 26 to 30 (AOR, 0.32; 95% CI, 0.26–0.40). Test use was lower for blacks, community centers, uninsured/governmentally insured patients, higher tumor grade, larger tumor size, and more nodes involved. Chemotherapy recommendation was higher for patients of younger age, with private insurance, and with higher tumor grade, size, and number of nodes involved. Black patients had significantly higher RS (AOR, 1.37; 95% CI, 1.25–1.79). Conclusions: The RS assay influences clinicians' chemotherapy recommendation in node-positive EBC. Clinicians are using the inclusion criteria of the RxPONDER trial before its final release. Black patients have higher RS, likely representing worse biology. Significant differences exist in test use and clinical implications based on race, insurance, and facility.
Jagar Jasem, Christine M. Fisher, Arya Amini, Elena Shagisultanova, Rachel Rabinovitch, Virginia F. Borges, Anthony Elias and Peter Kabos
Richard Li, Wei-Hsien Hou, Joseph Chao, Yanghee Woo, Scott Glaser, Arya Amini, Rebecca A. Nelson and Yi-Jen Chen
Background: Limited data are available to guide management of patients with stage I–III gastric cancer not undergoing potentially curative surgical resection. We compared survival outcomes associated with chemotherapy alone versus chemoradiation (CRT) in the treatment of nonmetastatic gastric cancer. Methods: Patients with gastric adenocarcinoma from 2004 to 2015 were identified using the National Cancer Database. Patients were excluded if they had surgery, metastatic disease, or T0, Tis, or T1a disease. Logistic regression was used to evaluate predictors of CRT use. Cox proportional hazards modeling was performed to compare overall survival (OS) between chemotherapy alone and CRT in overall and propensity score–matched cohorts. Results: We identified 4,795 patients with stage I–III gastric adenocarcinoma who did not undergo surgery, at a median follow-up of 11.8 months. A total of 3,316 patients (69.2%) received chemotherapy alone and 1,479 patients (30.8%) received CRT. Predictors of increased CRT use were age ≥65 years (odds ratio [OR] 1.68; 95% CI, 1.43–1.99; P<.001), Charlson-Deyo comorbidity score ≥2 (OR, 1.46; 95% CI, 1.18–1.81), and treatment at a community facility (OR, 1.27; 95% CI, 1.07–1.51; P=.006). Patients receiving CRT had a 2-year OS rate of 28.3% compared with 21.5% among those receiving chemotherapy. Multivariate analysis showed that CRT was associated with improved OS (hazard ratio [HR], 0.82; 95% CI, 0.77–0.89; P<.001). After propensity score matching, a persistent survival benefit was observed (HR, 0.80; 95% CI, 0.74–0.88; P<.001). Conclusions: In patients with stage I–III gastric cancer not undergoing surgical resection, CRT was associated with improved survival compared with chemotherapy alone. However, only 30.8% of patients received CRT in this setting.
Ashwin Shinde, Richard Li, Arya Amini, Yi-Jen Chen, Mihaela Cristea, Wenge Wang, Mark Wakabyashi, Ernest Han, Catheryn Yashar, Kevin Albuquerque, Sushil Beriwal and Scott Glaser
Background: Vulvar cancer with pelvic nodal involvement is considered metastatic (M1) disease per AJCC staging. The role of definitive therapy and its resulting impact on survival have not been defined. Patients and Methods: Patients with pelvic lymph node–positive vulvar cancer diagnosed in 2009 through 2015 were evaluated from the National Cancer Database. Patients with known distant metastatic disease were excluded. Logistic regression was used to evaluate use of surgery and radiation therapy (RT). Overall survival (OS) was evaluated with log-rank test and Cox proportional hazards modeling (multivariate analysis [MVA]). A 2-month conditional landmark analysis was performed. Results: A total of 1,304 women met the inclusion criteria. Median follow-up was 38 months for survivors. Chemotherapy, RT, and surgery were used in 54%, 74%, and 62% of patients, respectively. Surgery was associated with prolonged OS (hazard ratio [HR], 0.58; P<.001) but had multiple significant differences in baseline characteristics compared with nonsurgical patients. In patients managed nonsurgically, RT was associated with prolonged OS (HR, 0.66; P=.019) in MVA. In patients undergoing surgery, RT was associated with better OS (3-year OS, 55% vs 48%; P=.033). Factors predicting use of RT were identified. MVA revealed that RT was associated with prolonged OS (HR, 0.75; P=.004). Conclusions: In this cohort of women with vulvar cancer and positive pelvic lymph nodes, use of RT was associated with prolonged survival in those who did not undergo surgery. Surgery followed by adjuvant RT was associated with prolonged survival compared with surgery alone.
Richard Li, Ashwin Shinde, Marwan Fakih, Stephen Sentovich, Kurt Melstrom, Rebecca Nelson, Scott Glaser, Yi-Jen Chen, Karyn Goodman and Arya Amini
Background: Anal adenocarcinoma is a rare malignancy with a poor prognosis, and no randomized data are available to guide management. Prior retrospective analyses offer differing conclusions on the benefit of surgical resection after chemoradiotherapy (CRT) in these patients. We used the National Cancer Database (NCDB) to analyze survival outcomes in patients undergoing CRT with and without subsequent surgical resection. Methods: Patients with adenocarcinoma of the anus diagnosed in 2004 through 2015 were identified using the NCDB. Patients with metastatic disease and survival <90 days were excluded. We analyzed patients receiving CRT and stratified by receipt of surgical resection. Logistic regression was used to evaluate predictors of use of surgery and to form a propensity score–matched cohort. Overall survival (OS) was compared between treatment strategies using Cox proportional hazards regression. Results: We identified 1,747 patients with anal adenocarcinoma receiving CRT, of whom 1,005 (58%) received surgery. Predictors of increased receipt of surgery included age <65 years, private insurance, overlapping involvement of the anus and rectum, N0 disease, and external-beam radiation dose ≥4,000 cGy. With a median follow-up of 3.5 years, 5-year OS was 61.1% in patients receiving CRT plus surgery compared with 39.8% in patients receiving CRT alone (log-rank P<.001). In multivariate analysis, surgery was associated with significantly improved OS (hazard ratio, −0.59; 95% CI, 0.50–0.68; P<.001). This survival benefit persisted in a propensity score–matched cohort (log-rank P<.001). Conclusions: In the largest series of anal adenocarcinoma cases to date, treatment with CRT followed by surgery was associated with a significant survival benefit compared with CRT alone in propensity score–matching analysis. Our findings support national guideline recommendations of neoadjuvant CRT followed by resection for patients with anal adenocarcinoma.