Jessup, J. Milburn

4515 Background: INT0116 (SWOG 9008) was a prospectively randomized phase III trial of postoperative adjuvant therapy utilizing 5-FU/leucovorin plus external beam radiation in 582 eligible cases of resected stage IB-IV(M0) stomach and gastroesophageal junction cancers. Initial results (NEJM 345: 725, 2001) showed both overall and disease free survivals improved by chemoradiation. Methods:We now report INT0116 results with >10years median follow-up. Exploratory subset outcomes are also reported. Results: INT0116 continues to show benefit for chemoradiation with hazard ratios (HR) for survival (HR=1.32, p=.004) and disease free survival (HR=1.51, p<.001) favoring chemoradiation. Subset analyses were performed for sex, race, T and N stage, D-level of surgical resection, tumor location (proximal or other), histology (intestinal or diffuse) and Maruyama index. Chemoradiation benefited all subsets with the exceptions of women and diffuse histology. In women the HR for therapy was 1.0(0.68–1.45). The HR for therapy in diffuse histology cases was 0.97(0.62–1.40). Interaction between these factors is suggested as women were significantly more likely to have diffuse histology than men (56% versus 33%). A multivariate analysis of sex and histology did not detect an effect of sex once histology was included. These data suggest that sex may not be an independent variable for lack of response to chemoradiation but that diffuse histology may be. Long term toxicities were examined. Thirty-five second tumors occurred in 31 cases. Twenty-two occurred in chemoradiation cases and 9 in surgery only cases. Second tumors represented a spectrum of types of neoplasms commonly occurring in this age group (median age 60 years). Excessive numbers of tumors known to be caused by radiation and/or chemotherapy were not noted. More tumors may have occurred in the treated patients since their death rates were less than surgery only cases. Conclusions: With >10 years median follow-up, survival remains improved in stage IB-IV (M0) gastric cancer cases treated with post-operative chemoradiaiton. All subsets benefit from this treatment with the exception of cases with diffuse histology. Women may be more likely to have diffuse histology gastric cancers. No increases in late toxic effects were noted. No significant financial relationships to disclose.

Abstract Treatment of myeloma has benefited from the introduction of more effective and better tolerated agents, improvements in supportive care, better understanding of disease biology, revision of diagnostic criteria, and new sensitive and specific tools for disease prognostication and management. Assessment of minimal residual disease (MRD) in response to therapy is one of these tools, as longer progression-free survival (PFS) is seen consistently among patients who have achieved MRD negativity. Current therapies lead to unprecedented frequency and depth of response, and next-generation flow and sequencing methods to measure MRD in bone marrow are in use and being developed with sensitivities in the range of 10−5 to 10−6 cells. These technologies may be combined with functional imaging to detect MRD outside of bone marrow. Moreover, immune profiling methods are being developed to better understand the immune environment in myeloma and response to immunomodulatory agents while methods for molecular profiling of myeloma cells and circulating DNA in blood are also emerging. With the continued development and standardization of these methodologies, MRD has high potential for use in gaining new drug approvals in myeloma. The FDA has outlined two pathways by which MRD could be qualified as a surrogate endpoint for clinical studies directed at obtaining accelerated approval for new myeloma drugs. Most importantly, better understanding of MRD should also contribute to better treatment monitoring. Potentially, MRD status could be used as a prognostic factor for making treatment decisions and for informing timing of therapeutic interventions. Clin Cancer Res; 23(15); 3980–93. ©2017 AACR.

Purpose The sixth edition of the American Joint Committee on Cancer (AJCC) rectal cancer staging subdivided stage II into IIA (T3N0) and IIB (T4N0) and stage III into IIIA (T1-2N1M0), IIIB (T3-4N1M0), and IIIC (anyTN2M0). Subsequent analyses supported revised substaging of stage III as a result of improved survival with T1-2N2 versus T3-4N2 and survival of T4N1 more similar to T3-4N2 than T3N1. The AJCC Hindgut Taskforce sought population-based validation that depth of invasion interacts with nodal status to affect survival. Methods Surveillance, Epidemiology, and End Results (SEER) population-based data from January 1992 to December 2004 for 35,829 patients with rectal cancer were compared with rectal pooled analysis data (3,791 patients). T4N0 cancers were stratified by tumors that perforate visceral peritoneum (T4a) versus tumors that invade or are adherent to adjacent organs or structures (T4b). N1 and N2 were stratified by number of positive nodes as follows: N1a/N1b (one v two to three nodes) and N2a/N2b (four to six v ≥ seven nodes). Five-year observed and relative survival rates were obtained for each TN category. Results SEER rectal cancer analyses confirm that T1-2N2 cancers have better prognosis than T3-4N2, T4bN1 have similar prognosis to T4N2, T1-2N1 have similar prognosis to T2N0/T3N0, and T1-2N2a have similar prognosis to T2N0/T3N0 (T1N2a) or T4aN0 (T2N2a). Prognosis for T4a lesions is better than T4b by N category. The number of positive nodes affects prognosis. Conclusion This SEER population-based rectal cancer analysis validates the rectal pooled analyses and supports the shift of T1-2N2 lesions from IIIC to IIIA or IIIB and T4bN1 from IIIB to IIIC. SEER outcomes support subdividing T4, N1, and N2 and revised substaging of stages II and III. Survival by TN category suggests a complex biologic interaction between depth of invasion and nodal status.

Purpose The sixth edition of American Joint Committee on Cancer (AJCC) Cancer Staging Manual for colon cancer subdivided stage II into IIA (T3N0) and IIB (T4N0) and stage III into IIIA (T1-2N1M0), IIIB (T3-4N1M0), and IIIC (anyTN2M0). Subsequent analyses supported revised substaging of stage III because of improved survival for T1-2N2 versus T3-4N2 and T4N1 survival was more similar to T3-4N2 than to T3N1. The AJCC Hindgut Taskforce sought population-based validation that depth of invasion and nodal status interact to affect survival. Patients and Methods Surveillance, Epidemiology, and End Results (SEER) population-based data from January 1992 to December 2004 for 109,953 colon cancer patients were compared with National Cancer Data Base (NCDB) data on 134,206 patients. T4N0 cancers were stratified by tumors that perforate visceral peritoneum (T4a) versus tumors that invade or are adherent to adjacent organs or structures (T4b). N1 and N2 were stratified by number of involved positive lymph nodes (N+): N1a/N1b (1 v 2-3), N2a/N2b (4 to 6 v ≥ 7). Five-year observed and relative survival data were obtained for each TN category. Results SEER colon cancer analyses confirm that patients with T1-2N0 cancers have better survival than T3N0, T3N0 better than T4N0, T1-2N2 better than T3-4N2, and T4bN1 similar to T4N2. Patients with T4a lesions have better survival than T4b by N category. The number of positive nodes affects survival for each T category. Conclusion This SEER population-based colon cancer analysis is highly consistent with rectal cancer pooled analysis and SEER rectal cancer analyses, supporting the shift of T1-2N2 lesions from IIIC to IIIA/IIIB, shifting T4bN1 from IIIB to IIIC, subdividing T4/N1/N2, and revising substaging of stages II/III. Survival outcomes by TN category for colon and rectal cancer are strikingly similar.