Impact of body-mass index on treatment and outcome in locally advanced rectal cancer: A secondary, post-hoc analysis of the CAO/ARO/AIO-04 randomized phase III trial.

BACKGROUND: A better understanding of the impact of body-mass index (BMI) on the course of multimodal therapy and oncologic outcome in locally advanced rectal cancer could provide new insights for optimization of treatment and supportive strategies. PATIENTS AND METHODS: Correlations of BMI with pretreatment clinical, surgical, and pathological characteristics, toxicity and treatment adherence using the Pearson's Chi-squared test or logistic regression were analyzed in the CAO/ARO/AIO-04 III trial cohort (n = 1236). One-way ANOVA or Welch test were used to analyze correlations of baseline blood-parameters and BMI. The prognostic role of BMI was examined with log-rank test and multivariate cox regression. RESULTS: Obese had a better ECOG performance status (P = 0.027) but were less likely to undergo sphincter preserving surgery (P = 0.01). Post-surgical complications did not differ significantly between BMI classes, whereas underweight was associated with increased neutrophil (P = 0.025) and platelet counts (P < 0.001), poorer TME quality (P = 0.007) and increased incidence of acute organ toxicity (P < 0.001). After a median follow-up of 50 months, underweight [HR 1.896, P = 0.014] and overweight [HR 1.392, P = 0.042] were associated with worse DFS. Obese patients had an increased risk of death [HR 1.653, P = 0.032]. Normalweight men showed superior OS compared to underweight [HR 4.070, P = 0.002], overweight [HR 2.077, P = 0.010], severe overweight [HR 1.886, P = 0.026] and obese [HR 2.046, P = 0.015] men. Adding oxaliplatin to standard CRT significantly improved DFS in obese patients (P = 0.034). CONCLUSION: In our study, underweight and overweight correlated with inferior DFS, underweight experienced more organ toxicity and obesity was associated with an increased risk of abdominoperineal resection and poorer overall survival.

Association of Polo-Like Kinase 3 and PhosphoT273 Caspase 8 Levels With Disease-Related Outcomes Among Cervical Squamous Cell Carcinoma Patients Treated With Chemoradiation and Brachytherapy.

Introduction: Definitive chemoradiation (CRT) followed by high-dose-rate (HDR) brachytherapy (BT) represents state-of-the-art treatment for locally-advanced cervical cancer. Despite use of this treatment paradigm, disease-related outcomes have stagnated in recent years, indicating the need for biomarker development and improved patient stratification. Here, we report the association of Polo-like kinase (PLK) 3 expression and Caspase 8 T273 phosphorylation levels with survival among patients with cervical squamous cell carcinoma (CSCC) treated with CRT plus BT. Methods: We identified 74 patients with FIGO Stage Ib to IVb cervix squamous cell carcinoma. Baseline immunohistochemical scoring of PLK3 and pT273 Caspase 8 levels was performed on pre-treatment samples. Correlation was then assessed between marker expression and clinical endpoints, including cumulative incidences of local and distant failure, cancer-specific survival (CSS) and overall survival (OS). Data were then validated using The Cancer Genome Atlas (TCGA) dataset. Results: PLK3 expression levels were associated with pT273 Caspase 8 levels (p = 0.009), as well as N stage (p = 0.046), M stage (p = 0.026), and FIGO stage (p = 0.001). By the same token, pT273 Caspase 8 levels were associated with T stage (p = 0.031). Increased PLK3 levels corresponded to a lower risk of distant relapse (p = 0.009), improved CSS (p = 0.001), and OS (p = 0.003). Phospho T273 Caspase 8 similarly corresponded to decreased risk of distant failure (p = 0.021), and increased CSS (p < 0.001) and OS (p < 0.001) and remained a significant predictor for OS on multivariate analysis. TCGA data confirmed the association of low PLK3 expression with resistance to radiotherapy and BT (p < 0.05), as well as increased propensity for metastasis (p = 0.019). Finally, a combined PLK3 and pT273 Caspase 8 score predicted for decreased distant relapse (p = 0.005), and both improved CSS (p < 0.001) and OS (p < 0.001); this combined score independently predicted distant failure (p = 0.041) and CSS (p = 0.003) on multivariate analyses. Conclusion: Increased pre-treatment tumor levels of PLK3 and pT273 Caspase 8 correspond to improved disease-related outcomes among cervical cancer patients treated with CRT plus BT, representing a potential biomarker in this context.