New horizons from novel therapies in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a relatively rare, but highly lethal cancer of the pleural mesothelial cells. Its pathoge-nesis is integrally linked to asbestos exposure. In spite of recent developments providing a more detailed understanding of the pathogenesis, the outcomes continue to be poor. To date, trimodality therapy involving surgery coupled with chemotherapy and/or radiotherapy remains the standard of therapy. The development of resistance of the tumor cells to radiation and several che-motherapeutic agents poses even greater challenges in the management of this cancer. Ionizing radiation damages cancer cell DNA and aids in therapeutic response, but it also activates cell survival signaling pathways that helps the tumor cells to overcome radiation-induced cytotoxicity. A careful evaluation of the biology involved in mesothelioma with an emphasis on the workings of pro-survival signaling pathways might offer some guidance for treatment options. This review focuses on the existing treatment options for MPM, novel treatment approaches based on recent studies combining the use of inhibitors which target different pro-survival pathways, and radiotherapy to optimize treatment.

The impact of total neo-adjuvant treatment on nonoperative management in patients with locally advanced rectal cancer: The evaluation of 66 cases.

BACKGROUND: The study aimed to assess if adherence to a total-neoadjuvant-treatment (TNT) protocol followed by observation(watch-and-wait) led to the successful nonoperative-management of low-rectal-cancer. METHODS: In this study, patients with primary, resectable-T3-T4, N0-N1 distal-rectal-adenocarcinoma underwent-chemoradiotherapy + consolidation-chemotherapy (TNT). During the-TNT-period, endoscopy, MRI, and FDG-PET/CT were performed. We allocated patients with complete-clinical-tumor-regression, who underwent endoscopy every two months, MRI every-four-months, and PET/CT every-six-months-after-treatment, to the observation-group(OG). All other patients were referred for surgery. The OG was followed-up. The primary endpoint was local tumor-ecurrence after allocation to the OG. RESULTS: Between 2015 and 2018, we enrolled 66-patients. Of 60-patients who were eligible to participate, 39 had complete-clinical-response(cCR) and were allocated to the OG, six underwent local-excision (LE), and 15 underwent total-mesorectal-excision (TME). The median follow-up duration was 22 (9-42) months. The local-recurrence-rate in the OG was 15.3%, and the LE and TME rates were 16.6% and 0%, respectively. All recurrence cases were salvaged through either LE or TME. The-distant-metastasis rate was 5.1%, 16.6%, and 12.5% in the OG, LE, and TME groups, respectively. The endoscopic negative-predictive-value(NPV) was 50%, and the positive-predictive-value(PPV) was 76.9% in the surgery group (LE + TME). MRI; NPV-50%, PPV-76.9%. PET/CT; NPV-100%, PPV-93.3%. Six patients(28.57%) from surgery group achieved complete pathological response (cPR). CONCLUSION: Our results indicated a high proportion of selected-rectal-cancers with-cCR after neo-adjuvant-therapy could potentially be managed non-operatively, and major surgery may be avoided.