Tumor regression grading after preoperative hyperfractionated radiotherapy/chemoradiotherapy for locally advanced rectal cancers: interim analysis of phase III clinical study.

We investigated the tumor regression grading (TRG) as a prognostic marker for disease-free survival (DFS) in patients with advanced rectal cancer treated within phase III randomized study (ClinicalTrials.gov Identifier: NCT01814969). The study is still recruiting prospective trial of preoperative hyperfractionated radiotherapy (HART) compared with concomitant hyperfractionated radiotherapy with co-administration of chemotherapy based on 5-FU (HART-CT) in patients with T2/N+ or T3/any N resectable rectal cancer. This preplanned interim analysis examined the pathological outcome in the group of 136 patients who were randomly assigned to HART (n=69) and HART-CT (n=67). The pelvis was irradiated twice a day (28 fractions of 1.5 Gy), with a minimal interfraction interval of 8 h to a total dose of 42 Gy over 18 days (HART) or mentioned scheme with concurrent chemotherapy: 5-FU 325 mg/m2 (bolus) on days 1-3 and days 16-18 (HART-CT). Surgery was performed 6-7 weeks after HART/HART-CT. Postoperative 5-FU-based chemotherapy was given to ypN positive patients. The TRG was recorded using the following 4-point scale: TRG0 (pCR) denoted no cancer cells; TRG1 was diagnosed when a few cancer foci had been seen in less than 10% of a tumor mass; TRG2 denoted cancer cells seen in 10-50% of a tumor mass; in order to diagnose TRG3, cancer cells had to be seen in more than 50% of a tumor mass. Multivariable analysis was performed using Cox regression models and Cox proportional hazard model was used in the survival analysis. The crude rate of patients with any serious acute 3 toxicity during the follow-up was 16% vs. 25% for HART and HART-CT. Twenty-two patients (16%) presented with postoperative complications. Anterior resection was performed in 52% vs. 62% for HART and HART-CT respectively (p=0.06). Of the 136 patients evaluable for pathologic response, there were 3 (4%) vs. 9 (13%), 16 (23%) vs. 24 (36%), 40 (58%) vs. 30 (45%), and 10 (15%) vs. 4 (6%) patients with TRG 0, 1, 2, and 3, respectively in HART vs. HART-CT, the difference was statistically significant p=0.002. The addition of 5-FU infusion to HART was not associated with statistically significant improved loco-regional relapse-free survival (LRC), metastasis-free survival (MFS), and DFS. Significant differences in the tumor regression grading (TRG) were found. Both LRC and DFS of rectal cancer patients treated with HART vs. HART-CT had favorable outcomes in the HART-CT arm. Also, the sphincter preservation rate tended to favor HART-CT.

Radiomic signature accurately predicts the risk of metastatic dissemination in late-stage non-small cell lung cancer.

Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and the median overall survival (OS) is approximately 2-3 years among patients with stage III disease. Furthermore, it is one of the deadliest types of cancer globally due to non-specific symptoms and the lack of a biomarker for early detection. The most important decision that clinicians need to make after a lung cancer diagnosis is the selection of a treatment schedule. This decision is based on, among others factors, the risk of developing metastasis. Methods: A cohort of 115 NSCLC patients treated using chemotherapy and radiotherapy (RT) with curative intent was retrospectively collated and included patients for whom positron emission tomography/computed tomography (PET/CT) images, acquired before RT, were available. The PET/CT images were used to compute radiomic features extracted from a region of interest (ROI), the primary tumor. Radiomic and clinical features were then classified to stratify the patients into short and long time to metastasis, and regression analysis was used to predict the risk of metastasis. Results: Classification based on binarized metastasis-free survival (MFS) was applied with moderate success. Indeed, an accuracy of 0.73 was obtained for the selection of features based on the Wilcoxon test and logistic regression model. However, the Cox regression model for metastasis risk prediction performed very well, with a concordance index (C-index) score equal to 0.84. Conclusions: It is possible to accurately predict the risk of metastasis in NSCLC patients based on radiomic features. The results demonstrate the potential use of features extracted from cancer imaging in predicting the risk of metastasis.

Randomised clinical trial on 7-days-a-week postoperative radiotherapy vs. concurrent postoperative radio-chemotherapy in locally advanced cancer of the oral cavity/oropharynx.

OBJECTIVE: To compare the efficacy and tolerance of 7-days-a-week accelerated postoperative radiotherapy (p-CAIR) vs postoperative radio-chemotherapy (p-RTCT). METHODS: Between September 2007 and October 2013, 111 patients were enrolled and randomly assigned to receive 63 Gy in 1.8 Gy fractions 7-days-a-week (n = 57, p-CAIR) or 63 Gy in 1.8 Gy fractions 5-days-a-week with concurrent cisplatin 80-100 mg per square meter of body-surface area on days 1, 22 and 43 of the radiotherapy course (p-RTCT). It represents approximately 40% of the intended trial size, that was closed prematurely due to slowing accrual. Only high-risk patients with squamous cell cancer of the oropharynx/oral cavity, considered fit for concurrent treatment were enrolled. RESULTS: The rate of locoregional control (LRC) did not differ significantly between treatment arms (p = 0.18, HR = 0.56), 5 year LRC tended, however, to favour p-RTCT (81%) vs p-CAIR (62%). There was no difference in overall survival between treatment arms (p = 0.90, HR = 1.03).The incidence and severity of acute mucosal reactions and late reactions did not differ significantly between treatment arms. Haematological toxicity of p-RTCT was, however, considerably increased compared to p-CAIR. CONCLUSION: Concurrent postoperative RTCT tended to improve locoregional control rate as compared to p-CAIR. This, however, did not transferred into improved overall survival. Postoperative RTCT was associated with a substantial increase in haematological toxicity that negatively affected treatment compliance in this arm. ADVANCES IN KNOWLEDGE: To our knowledge, this is the first trial that compares accelerated radiotherapy and radio-chemotherapy in postoperative treatment for oralcavity/oropharyngeal cancer.