A current comprehensive role of immune-checkpoint inhibitors in resectable non-small cell lung cancer: A narrative review.

OBJECTIVE: The objective of this article is to review the efficacy, safety, and evidence for current use and potential future uses of immune-checkpoint inhibitors (ICIs) in the management of resectable non-small cell lung cancer (NSCLC). DATA SOURCES: A literature review was carried out through PubMed to identify completed and ongoing clinical trials evaluating the use, efficacy, and safety of ICIs in the management of resectable NSCLC. DATA SUMMARY: To date, four phase 3 trials have emerged that have changed our treatment practice concerning the utilization of ICIs during the adjuvant and neoadjuvant settings. The IMpower010 and KEYNOTE-091 trials examined the application of adjuvant atezolizumab and pembrolizumab, respectively, following surgical resection and adjuvant chemotherapy. In the CheckMate 816 trial, the combination of nivolumab and chemotherapy as a neoadjuvant therapy received approval for patients with resectable NSCLC. Also, for patients with resectable NSCLC, the use of a pembrolizumab and chemotherapy combination as a perioperative therapy received approval based on the results of the KEYNOTE-671 trial. Apart from these trials, there are numerous phase 2 and phase 3 trials, some of which have been published while others are still in progress. CONCLUSION: Despite the promising outcomes from these trials there remain several unanswered questions. In this review, we will assess clinical trials involving adjuvant, neoadjuvant, and perioperative ICIs, aiming to address the unresolved questions related to these therapeutic approaches.

Expanding treatment options for resectable gastric cancer: Is it a countdown for radiotherapy?

Chemoradiotherapy (CRT) and chemotherapy in the perioperative or postoperative settings are the different neoadjuvant/adjuvant treatment approaches for resectable gastric cancer. After the results of the ARTIST trial, CRT lost its importance on a large scale in the adjuvant setting. Also, according to the results of the CRITICS trial, CRT does not seem beneficial in the perioperative treatment setting. The beneficial effect of neoadjuvant/adjuvant radiotherapy as a therapeutic option became more questionable as the evidence grows, but still needs further studies to identify its effects on a subgroup of patients who have R1 or

Targeting the PD-1 pathway: a new hope for gastrointestinal cancers.

BACKGROUND: VEGF, HER2 and EGFR targeted agents are currently used in gastric, esophageal and colorectal cancers. However, treatment outcomes are still poor in most gastrointestinal (GI) cancers. Immune checkpoints are one of the most promising immunotherapy approaches. In this review article, we aim to discuss the efficacy and safety of anti-PD-1/PD-L1 therapies in GI cancers, including gastric, esophageal and colorectal cancer in published or reported recent studies. SCOPE: A literature search was made from PubMed and ASCO Annual Meeting abstracts by using the following search keywords: "nivolumab", "pembrolizumab", "avelumab", "GI cancers" "anti-PD1 therapy" and "anti-PD-L1 therapy". The last search was on 2 November 2016. The most important limitation of our review is that most of the data on anti-PD-1/PD-L1 therapies in GI cancers relies on phase 1 and 2 trials. FINDINGS: Currently, there are two anti-PD-1 (nivolumab and pembrolizumab) and one anti-PDL1 (atezolizumab) agents approved by FDA. After the treatment efficacy of immune checkpoint blockade was shown in melanoma, renal cell cancer and non-squamous lung cancer, trials which evaluate immune checkpoint blockade in GI cancers are ongoing. Early results of trials have been promising and encouraging for patients with advanced stage gastroesophageal cancer. According to early results of published trials, response to anti-PD1/PD-L1 agents appears to be associated with tumor PD-L1 levels. According to two recently published phase 2 trials, the clinical benefits of immune checkpoint blockade with both nivolumab and pembrolizumab were limited in patients with microsatellite instability (MSI) positive advanced colorectal cancer. However, several phase 2/3 trials are still ongoing. CONCLUSION: Both pembrolizumab and nivolumab show promising efficacy with acceptable safety data in published trials in GI cancers, especially in refractory MSI positive metastatic colorectal cancer.

Evaluation of erectile dysfunction risk factors in young male survivors of colorectal cancer.

PURPOSE: Improved long-term survival of colorectal cancer patients (CRC) treated with surgery and/or chemotherapy ± radiotherapy (RT) has led to increased awareness of long-term side effects, including effecting sexual life, which can ultimately affect the quality of life in these patients. Because the absolute risk factors of erectile dysfunction (ED) have not been defined in CRC patients, the aim of this research was to identify the severity and the absolute risk factors of ED in male CRC survivors. METHODS: The medical records of 61 male survivors of CRC treated with surgery and/or chemotherapy ± RT were retrieved from the medical oncology outpatient clinics during routine follow-up visits in 2011-2012. Patients older than 55 years and those with ED history before diagnosis were excluded. International Index of Erectile Function (IIEF) questionnaire was filled in by the patients. RESULTS: The patient mean age was 47.6±6.7 years (range 18-55) at the time of filling in the questionnaire. According to the International Index of Erectile Function (IIEF) score, 83.6% of the patients had some degree of ED. The risk factors of erectile dysfunction were advancing age (p=0.01), tumor location (p=0.01), type of surgery (p=0.02), presence of stoma (p=0.03)) and RT (p=0.005). Chemotherapy didn't impact ED (p=0.46). Also, there was no significant correlation between smoking status, hypertension, diabetes mellitus, cardiovascular disease, stage of the tumor and ED. Also hormonal disturbances such as serum FSH, LH and testesterone levels did not affect the presence of ED. CONCLUSION: Overall, 83.6% of the male CRC survivors had some degree of ED according to the IIEF. The risk factors of ED were advancing age, tumor location, type of operation, presence of stoma and RT. Clinicians should be aware of these risk factors to offer their patients adequate treatment options and also come up with new treatment strategies necessary to reduce further ED in CRC survivors.