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.
Richard Li, Ashwin Shinde, Marwan Fakih, Stephen Sentovich, Kurt Melstrom, Rebecca Nelson, Scott Glaser, Yi-Jen Chen, Karyn Goodman and Arya Amini
Marsha Reyngold, Joyce Niland, Anna ter Veer, Dana Milne, Tanios Bekaii-Saab, Steven J. Cohen, Lily Lai, Deborah Schrag, John M. Skibber, William Small Jr, Martin Weiser, Neal Wilkinson and Karyn A. Goodman
Based on randomized data, neoadjuvant chemoradiotherapy has been incorporated into the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for stage II-III rectal cancer. Factors associated with nonadherence to evidence-based guidelines for neoadjuvant radiotherapy (RT) were examined at dedicated cancer centers. The prospective NCCN Oncology Outcomes Database for Colorectal Cancers was queried for patients with stage II-III rectal cancer who underwent a transabdominal surgical resection between September 2005 and June 2012. Multivariable logistic regression was used to identify factors associated with omission of RT. Among 1199 identified patients, 1119 (93%) received neoadjuvant RT, 51 (4%) did not receive RT, and 29 (2%) received adjuvant RT. Among 51 patients not receiving RT, only 19 (37%) were referred and evaluated by a radiation oncologist. On multivariable analysis, clinical factors associated with not receiving RT included a history of prior pelvic RT (adjusted odds ratio [aOR], 23.9; P=.0003), ECOG performance status of 2 or greater (aOR, 11.1; P=.01), tumor distance from the anal verge greater than 10 cm (aOR, 5.4; P=.009), age at diagnosis of 75 years or older (aOR, 4.43; P=.002), body mass index of 25 to 30 kg/m2 and less than 25 kg/m2 (aOR, 5.22 and 4.23, respectively; P=.03), and clinical stage II (aOR, 2.27; P=.02). No significant change was seen in RT use according to diagnosis year, nor was any correlation seen with distance to the nearest RT facility. Concordance with NCCN Guidelines for neoadjuvant RT is high among NCCN Member Institutions. After adjusting for clinical characteristics that increase the risk for RT toxicity, including history of pelvic RT and high comorbidity burden/low functional status, the authors found that non-obese patients of advanced age or those with more favorable clinical features were more likely to not receive RT.
Andrea Cercek, Karyn A. Goodman, Carla Hajj, Emily Weisberger, Neil H. Segal, Diane L. Reidy-Lagunes, Zsofia K. Stadler, Abraham J. Wu, Martin R. Weiser, Philip B. Paty, Jose G. Guillem, Garrett M. Nash, Larissa K. Temple, Julio Garcia-Aguilar and Leonard B. Saltz
Standard therapy for locally advanced rectal cancer (LARC) is preoperative chemoradiotherapy and postoperative chemotherapy. At Memorial Sloan-Kettering Cancer Center (MSKCC) the authors began offering FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) as initial treatment for patients with high-risk LARC to target micrometastases while treating the primary tumor. The purpose of this study is to report the safety and efficacy of initial FOLFOX given before chemoradiotherapy on tumor downsizing and pathologic complete response (pathCR) in LARC. The records of patients with stage II/III rectal cancer treated at MSKCC between 2007 and 2012 were reviewed. Of approximately 300 patients with LARC treated at MSKCC, 61 received FOLFOX as initial therapy. Of these 61 patients, 57 received induction FOLFOX (median 7 cycles) followed by chemoradiation, and 4 experienced an excellent response, declined chemoradiation, and underwent total mesorectal excision (TME). Twelve of the 61 patients did not undergo TME: 9 had a complete clinical response (CCR), 1 declined despite persistent tumor, 1 declined because of comorbidities, and 1 developed metastatic disease. Among the 61 patients receiving initial FOLFOX, 22 (36%) had either a pathCR (n=13) or a CCR (n=9). Of the 49 patients who underwent TME, all had R0 resections and 23 (47%) had tumor response greater than 90%, including 13 (27%) who experienced a pathCR. Of the 28 patients who received all 8 cycles of FOLFOX, 8 experienced a pathCR (29%) and 3 a CCR (11%). No serious adverse events occurred that required a delay in treatment during FOLFOX or chemoradiation. FOLFOX and chemoradiation before planned TME results in tumor regression, a high rate of delivery of planned therapy, and a substantial rate of pathCRs, and offers a good platform for nonoperative management in select patients.
Ashley E. Glode, S. Lindsey Davis, Supriya K. Jain, Megan D. Marsh, Lisa J. Wingrove, Tracey E. Schefter, Karyn Goodman, Lindel C.K. Dewberry, Martin D. McCarter, Laura Melton, Michelle Bunch, William T. Purcell and Stephen Leong
Background: At our institution, the standard treatment recommendation for esophageal cancer patients with stage IB–IIIB disease is for neoadjuvant chemoradiation per the CROSS regimen prior to surgery. This regimen can be difficult for patients to tolerate, and they may be unable to receive full dose therapy without treatment dose reductions and delays. Methods: We conducted a quality improvement (QI) project, STRENGTH (Seeking to Reactivate Esophageal and Gastric Treatment Health), to implement supportive care interventions in the prehabilitation phase of neoadjuvant treatment. Our QI program included a standardized chemotherapy order template with supportive care interventions implemented at specific time points. Following implementation of the STRENGTH pathway, a retrospective QI analysis assessed an equal number of patients in the pre-STRENGTH and STRENGTH group for chemotherapy and radiation therapy dose intensities, as well as treatment outcomes. Results: During the pre-STRENGTH period, patients received an average of 5 chemotherapy treatments (range, 2–6), with an average relative dose intensity of 91.8% for carboplatin and 86.7% for paclitaxel. During the STRENGTH period, patients received an average of 6 (range, 5–8) chemotherapy treatments, with an average relative dose intensity of 111.4% for carboplatin and 112.9% for paclitaxel. In the pre-STRENGTH group, one patient did not complete their planned radiation dose due to nausea, vomiting, and dehydration. All patients in the STRENGTH group received their planned radiation dose. In the STRENGTH group, there is a trend of improved pathologic response, longer progression-free survival, and shortened time to surgery. Conclusion: Implementation of the STRENGTH pathway improved chemotherapy dose intensity, with potentially improved oncologic outcomes in the STRENGTH group. We plan to further optimize the STRENGTH program with implementation of standardized dose reduction and delay protocols for both chemotherapy and radiation, and assess the effects of STRENGTH interventions on patient quality of life.