Background: Chemotherapy with or without pelvic radiotherapy (RT) is included in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for metastatic anal cancer (MAC), despite limited clinical evidence for RT in this setting. In addition, increasing evidence shows that local therapies, including RT, may increase patient survival for some types of metastatic cancers. The purpose of this study was to evaluate the patterns of care and association between definitive pelvic RT and overall survival (OS) for patients with MAC. Methods: The National Cancer Database was analyzed to evaluate OS of patients with newly diagnosed MAC treated with chemotherapy with or without pelvic RT. Those who did not undergo treatment, treated with surgery, or without baseline variables were excluded. OS was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score–matched analyses. Results: From 2004 through 2015, 437 patients received chemotherapy alone and 1,020 received pelvic chemoradiotherapy (CRT). At a median follow-up of 17.3 months, CRT was associated with improved OS on univariate (P<.001) and multivariate analysis (hazard ratio [HR], 0.70; 95% CI, 0.61–0.81; P<.001). Propensity score–matched analysis demonstrated superior median survival (21.3 vs 15.9 months) and 2-year OS rates (46% vs 34%) with CRT compared with chemotherapy alone (P<.001). Landmark analyses limited to long-term survivors of ≥1, ≥2, and ≥4 years showed improved OS with CRT in all subsets (all P<.05). CRT with therapeutic doses (≥45 Gy) was associated with longer median survival than palliative doses (<45 Gy) and chemotherapy alone (24.9 vs 10.9 vs 15.6 months, respectively; P<.001). The benefit of CRT was present among not only those with distant lymph node metastasis (HR, 0.63; P=.04) but also those with distant organ disease (HR, 0.74; P<.001). Conclusions: In this large hypothesis-generating analysis, patients with newly diagnosed MAC who received definitive pelvic RT with chemotherapy lived significantly longer than those who received chemotherapy alone. Prospective trials evaluating definitive local RT for MAC are warranted.
Yuefeng Wang, Xinhua Yu, Nan Zhao, Jiajing Wang, Chi Lin, Enrique W. Izaguirre, Michael Farmer, Gary Tian, Bradley Somer, Nilesh Dubal, David L. Schwartz, Matthew T. Ballo, and Noam A. VanderWalde
Ling-Long Tang, Yu-Pei Chen, Yan-Ping Mao, Zi-Xian Wang, Rui Guo, Lei Chen, Li Tian, Ai-Hua Lin, Li Li, Ying Sun, and Jun Ma
Background: In this study, we evaluated the 8th edition of the Union for International Cancer Control (UICC)/AJCC staging system for nasopharyngeal carcinoma (NPC) in an endemic area, with the aim of validating its applicability and providing further information for future refinements. Methods: A total of 1,790 patients with newly diagnosed, non–distant metastatic, histologically proven NPC treated with intensity-modulated radiotherapy (IMRT) were retrospectively reviewed. The performance of various staging systems was compared using the Akaike information criterion (AIC) and Harrell's concordance index (c-index). Results: For N (node) category, the survival curves of different groups according to the 8th edition were well-separated, and the prognostic model predicted outcomes fairly well. The 8th edition had higher AIC and c-index values for all end points than the 7th edition. However, probably due to the improved locoregional control provided by IMRT, the survival curves for T2 and T3 almost overlapped, without significant differences in locoregional failure-free survival (P=.606) and disease-free survival (P=.735). Due to the difficultly of differentiating T2 and T3, the AIC and c-index values were similar for the T categories of the 7th and 8th editions. Similarly, the overall survival and disease-free survival curves for stage II and III disease were not clearly separated for either the 8th or 7th editions. Conclusions: The 8th edition of the UICC/AJCC staging system for NPC enables more accurate prediction of treatment outcomes. However, several limitations need to be addressed in future editions, and it would be reasonable to further optimize the T category classification.
Yu Tian, Elham Kharazmi, Hermann Brenner, Xing Xu, Kristina Sundquist, Jan Sundquist, and Mahdi Fallah
Background: The aim of this study was to explore the risk of invasive colorectal cancer (CRC) in relatives of patients with colorectal carcinoma in situ (CCIS), which is lacking in the literature. Patients and Methods: We collected data from Swedish family-cancer datasets and calculated standardized incidence ratio (SIR) and cumulative risk of CRC in family histories of CCIS in first- and second-degree relatives. Family history was defined as a dynamic (time-dependent) variable allowing for changes during the follow-up period from 1958 to 2015. Of 12,829,251 individuals with available genealogical data, 173,796 were diagnosed with CRC and 40,558 with CCIS. Results: The lifetime (0–79 years) cumulative risk of CRC in first-degree relatives of patients with CCIS was 6.5%, which represents a 1.6-fold (95% CI, 1.5–1.7; n=752) increased risk. A similarly increased lifetime cumulative risk (6.7%) was found among first-degree relatives of patients with CRC (SIR, 1.6; 95% CI, 1.6–1.7; n=6,965). An increased risk of CRC was also found in half-siblings of patients with CCIS (SIR, 1.9; 95% CI, 1.1–3.0; n=18) and also in half-siblings of patients with CRC (SIR, 1.7; 95% CI, 1.3–2.1; n=78). Moreover, the increased risk of CRC was higher for younger age at diagnosis of CCIS in the affected first-degree relative and for younger age at diagnosis of CRC in the index person. Conclusions: Results of this study show that first-degree relatives and half-siblings of patients with CCIS have an increased risk of CRC, which is comparable in magnitude to the risk of those with a family history of invasive CRC. These findings extend available evidence on familial risk of CRC and may help to refine guidelines and recommendations for CRC screening.