Impact of Travel Distance and Urban-Rural Status on the Multidisciplinary Management of Rectal Cancer.

OBJECTIVES: Optimal treatment of rectal cancer (RC) requires multidisciplinary care. We examined whether distance to treatment center or community size impacts access to multimodality care and population-based outcomes in RC. METHODS: Patients diagnosed with stage II/III RC from 1999 to 2009 and treated at 1 of 6 regional cancer centers in British Columbia were reviewed. Distance to treatment center was determined for each patient. Communities were classified as rural, small, medium, and large population centers. Logistic and Cox regression models assessed associations of distance and community size with treatment received as well as cancer-specific (CSS) and overall survival (OS). RESULTS: Of 3,158 patients, 93.6% underwent surgery, 86.3% received radiotherapy, and 51.3% were treated with adjuvant chemotherapy (AC). Median time from diagnosis to oncologic consultation was longer for those >100 km from a treatment center or residing in medium/rural communities. Logistic regression demonstrated no correlation between distance or community size and receipt of treatment modality. Univariate analysis showed similar CSS (P = .18, .88) and OS (P = .36, .47) based on community size and distance, respectively. In multivariate analysis, distance >100 km had inferior CSS (Hazard Ratio [HR] 1.39, 95% CI: 1.03-1.88; P = .031). There was no consistent trend between decreasing community size and outcomes; however, living in a small center was associated with improved OS (HR 0.58, 95% CI: 0.38-0.88; P = .011) and CSS (HR 0.42, 95% CI: 0.25-0.70; P = .001). CONCLUSIONS: In this population-based study, there were no urban-rural differences in access to multidisciplinary care, but increased distance may be associated with worse cancer-specific outcomes.

Immunoglobulin VH somatic hypermutation in mantle cell lymphoma: mutated genotype correlates with better clinical outcome.

Mantle cell lymphoma is an aggressive B-cell lymphoma for which the biology is incompletely understood. Previous studies have reported that somatic hypermutation of the variable region of the immunoglobulin heavy chain gene (V(H)), as commonly defined as <98% homology, can be detected in approximately one-third of mantle cell lymphoma, although the V(H) mutation status has not been found to significantly correlate with patient survival. In this study, we assessed V(H) mutation in 55 mantle cell lymphomas using a method slightly different from those used in the previous studies, and we came to different conclusions. Using DNA extracted from formalin-fixed/paraffin-embedded tumors in all cases, we identified monoclonal IGH bands in 54 of 55 cases with the FR1c/J(H) primer; a monoclonal IGH band was amplified using another IGH primer set, FR256/J(H), in the remaining case. Cloning was performed in all cases, and an average of six clones were sequenced and analyzed for each case. Intraclonal heterogeneity was detected in 45 (82%) cases. Further analysis was performed in 53 cases, in which a predominant IGH species was identified. Most (32 of 53 cases, 60%) cases were 'mutated', with <98% homology. V(H)1-69, V(H)4-59 and V(H)3-74 were utilized in 29 (55%) cases. Intraclonal evolution and non-productive V(H) rearrangements were more frequent in the mutated group. Patients with the 'mutated' genotype had longer overall survival (P=0.017, Log rank) that is independent of the international prognostic index. To conclude, our data suggest that the V(H) mutation frequency in mantle cell lymphoma may be higher than previously believed. Importantly, using our methodology, we found that the V(H) mutation status may be a useful prognostic marker for these patients.