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Differential tumor response to therapy is partially attributed to tumor heterogeneity. Additional efforts are needed to identify tumor heterogeneity parameters in response to therapy that is easily applicable in clinical practice. We aimed to describe tumor response-speed heterogeneity and evaluate its prognostic value in patients with metastatic colorectal cancer.Individual patient data from Amgen (NCT00364013) and Sanofi (NCT00305188; NCT00272051) trials were retrieved from Project Data Sphere. Patients in the Amgen 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX) arm were used to establish response-speed heterogeneity. Its prognostic value was subsequently validated in the Sanofi FOLFOX arms and the Amgen panitumumab+FOLFOX arm. Kaplan-Meier method and Cox proportional hazards models were used for survival analyses.Patients with high response-speed heterogeneity in the Amgen FOLFOX cohort had significantly shorter (P0.001) median progression-free survival (PFS) of 7.27 months (95% CI, 6.12-7.96 mo) and overall survival (OS) of 16.0 months (95% CI, 13.8-18.2 mo) than patients with low response-speed heterogeneity with median PFS of 9.41 months (95% CI, 8.75-10.89 mo) and OS of 22.4 months (95% CI, 20.1-26.7 mo), respectively. Tumor response-speed heterogeneity was a poor prognostic factor of shorter PFS (hazard ratio, 4.17; 95% CI, 2.49-6.99; P0.001) and shorter OS (hazard ratio, 2.57; 95% CI, 1.64-4.01; P0.001), after adjustment for other common prognostic factors. Comparable findings were found in the external validation cohorts.Tumor response-speed heterogeneity to first-line chemotherapy was a novel prognostic factor associated with early disease progression and shorter survival in patients with metastatic colorectal cancer.

Background US health care is increasingly defined by over expenditure and inefficiency. Optimizing patient follow-up is critical, especially in cancers treated with high control rates. To optimize patient care, this study assessed time to disease recurrence or toxicity in patients with anal carcinoma. Materials and methods In total, 140 patients with biopsy-proven, nonmetastatic anal carcinoma, treated with chemoradiation utilizing intensity-modulated radiation therapy, were identified from our institutional database. This retrospective study evaluated local recurrence (LR), distant metastasis (DM), overall survival (OS), and late ≥grade 3 toxicity (LG3T). Patients were followed posttreatment every 3 months for 2 years, every 6 months in years 3 to 5, then yearly thereafter per NCCN recommendations. Results The median age and follow-up was 58 years and 27 months, respectively. Patients were categorized into high (n=61; 44%) and low (n=77; 55%) risk groups based on stage. The 2-year LC, DMFS, and OS were 93%, 94%, and 89% and 5-year LC, DMFS, OS were 92%, 87%, and 85%, respectively. Overall, there were 29 events (9 LR, 11 DM, and 9 LG3T), with 62% of events occurring within year 1 and 79% within 2 years. Stratified by event type, at 2 years 89% of LR, 64% of DM, and 89% LG3T were identified. At the remaining follow-up points, the event incidence rate was 1.3%. Conclusion With the majority of recurrences/toxicities occurring within the first 2 years, a reduction in follow-up during years 3 to 5 may provide adequate surveillance. Revisions of the current recommendations could maximize resources while improving patient quality of life.

Objectives Early-phase clinical trials play a pivotal role in drug development. However, limited data are available on outcomes of gastrointestinal (GI) cancer patients enrolled in phase I clinical trials. Here, we evaluated the characteristics associated with survival in GI cancer patients participating in phase I clinical trials and attempted to validate previously established prognostic models. Materials and methods All consecutive patients with advanced GI tumors who participated in phase I clinical trials at our institution from January 2007 to December 2013 and received at least 1 dose of the study drug were included. Cox regression models were used to estimate multivariable-adjusted hazard ratio (HR) and 95% confidence interval. Results In 243 study patients (median age, 62 y [range, 26 to 82 y]; 55% male), treatment included chemotherapy only (14%), targeted therapy (41%), chemotherapy+targeted therapy (42%), and others (2%) for the following disease types: pancreatic (42%), colorectal (34%), gastroesophageal (10%), hepatobiliary (13%), and others (2%). Response rate was 4%, with 38% achieving stable disease and 42% having progressive disease. Median survival was 5.8 months (range, 0.2 to 52.4 mo). Our multivariable Cox regression analyses included the following as predictors of survival: Eastern Cooperative Oncology Group performance score ≥1 (HR=1.76), prior systemic therapies ≥2 (HR=1.63), lactate dehydrogenase >618 IU/L (HR=1.85), sodium >135 mmol/L (HR=0.46), and white blood count >6×10/L (HR=1.5). Our data set was consistent with previous prognostic scores. Conclusions This is the largest study to assess clinical outcomes in this patient population. Phase I trials provide clinical benefit to patients with advanced GI malignancies and should be recommended as a treatment option in appropriate patients.

Advanced hepatocellular cancer (HCC) is an incurable disease with limited options for systemic treatment. Sorafenib was approved for advanced HCC based on trials in patients with Child-Pugh class A. We reviewed our experience retrospectively in patients with HCC who were treated with sorafenib with a focus on Child-Pugh B (CP-B) liver cirrhosis and effect of hypertension (HTN) on survival.We retrospectively reviewed medical charts of patients with documented advanced HCC who received sorafenib since 2007. Survival data were plotted according to Child-Pugh class and HTN.Results of 41 patients 39% had CP-B. Eighty-five percent were male and 67% had HCC due to viral hepatitis. Fifty-six percent received localized treatment before sorafenib. Five percent had a partial response and 39% had stable disease. Time to progression and overall survival (OS) for all patients were 3.2 and 6.2 months, respectively. Time to progression and OS were 4 and 8.4 months in Child-Pugh class A patients and 2 and 3.2 months in CP-B patients, which were statistically significant. Patients who had documented HTN while on treatment according to Common Terminology Criteria for Adverse Events version 3.0 had significantly better OS (18.2 vs. 4.5 mo; P=0.016).Development of HTN with sorafenib seems to be associated with a favorable effect on prognosis. Future trials should examine this observation.