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Background Metformin slows tumor growth and progression in vitro, and in combination with chemoradiotherapy, resulted in high overall survival in patients with head and neck cancer squamous cell carcinoma (HNSCC) in our phase 1 clinical trial (NCT02325401). Metformin is also postulated to activate an antitumor immune response. Here, we investigate immunologic effects of metformin on natural killer (NK) and natural killer T cells, including results from two phase I open-label studies in patients with HNSCC treated with metformin (NCT02325401, NCT02083692).Methods Peripheral blood was collected before and after metformin treatment or from newly diagnosed patients with HNSCC. Peripheral immune cell phenotypes were evaluated using flow cytometry, cytokine expression by ELISA and/or IsoLight, and NK cell-mediated cytotoxicity was determined with a flow-based NK cell cytotoxicity assay (NKCA). Patient tumor immune infiltration before and after metformin treatment was analyzed with immunofluorescence. NK cells were treated with either vehicle or metformin and analyzed by RNA sequencing (RNA-seq). NK cells were then treated with inhibitors of significant pathways determined by RNA-seq and analyzed by NKCA, ELISA, and western blot analyses.Results Increased peripheral NK cell activated populations were observed in patients treated with metformin. NK cell tumor infiltration was enhanced in patients with HNSCC treated with metformin preoperatively. Metformin increased antitumorigenic cytokines ex vivo, including significant increases in perforin. Metformin increased HNSCC NK cell cytotoxicity and inhibited the CXCL1 pathway while stimulating the STAT1 pathway within HNSCC NK cells. Exogenous CXCL1 prevented metformin-enhanced NK cell-mediated cytotoxicity. Metformin-mediated NK cell cytotoxicity was found to be AMP-activated protein kinase independent, but dependent on both mechanistic target of rapamycin and pSTAT1.Conclusions Our data identifies a new role for metformin-mediated immune antitumorigenic function through NK cell-mediated cytotoxicity and downregulation of CXCL1 in HNSCC. These findings will inform future immunomodulating therapies in HNSCC.

Abstract The COVID‐19 pandemic changed health‐care operations around the world and has interrupted standard clinical practices as well as created clinical research challenges for cancer patients. Cancer patients are uniquely susceptible to COVID‐19 infection and have some of the worst outcomes. Importantly, cancer therapeutics could potentially render cancer patients more susceptible to demise from COVID‐19 yet the poor survival outcome of many cancer diagnoses outweighs this risk. In addition, the pandemic has resulted in risks to health‐care workers and research staff driving important change in clinical research operations and procedures. Remote telephone and video visits, remote monitoring, electronic capture of signatures and data, and limiting sample collections have allowed the leadership in our institution to ensure the safety of our staff and patients while continuing critical clinical research operations. Here we discuss some of these unique challenges and our response to change that was necessary to continue cancer clinical research; and, the impacts the pandemic has caused including increases in efficiency for our cancer research office.

Renal angiomyolipoma (rAML) occurs rarely sporadically but is commonly encountered in patients with tuberous sclerosis complex and lymph-angioleiomyomatosis. rAML is a rare entity, not seen regularly in daily practice; however, is commonly encountered and diagnosed by clinicians who approach and treat kidney masses. Basic knowledge of this entity is necessary to recognize that despite being benign, these tumors can rarely cause deadly complications such as hemorrhage or severe renal dysfunction or may have malignant components associated with them.

IntroductionSurgery is the primary treatment for resectable, non-metastatic recurrent head and neck squamous cell carcinoma (HNSCC). We explore the safety and oncologic benefit of intraoperative Cesium-131 (Cs-131) brachytherapy combined with salvage local and/or regional surgical resection.Methods and MaterialsFindings were reported from a single arm multi-institutional prospective phase 1/2 trial involving surgery plus Cs-131 (surgery + Cs-131) treatment. The results of two retrospective cohorts—surgery alone and surgery plus intensity modulated radiation therapy (surgery + ReIMRT)—were also described. Included patients had recurrent HNSCC and radiation history. Safety, tumor re-occurrence, and survival were evaluated.ResultsForty-nine patients were enrolled in the surgery + Cs-131 prospective study. Grade 1 to 3 adverse events (AEs) occurred in 18 patients (37%), and grade 4 AEs occurred in 2 patients. Postoperative percutaneous endoscopic gastrostomy (PEG) tubes were needed in 10 surgery + Cs-131 patients (20%), and wound and vascular complications were observed in 12 patients (24%). No cases of osteoradionecrosis were reported in the surgery + Cs-131 cohort. We found a 49% 2-year disease-free survival at the site of treatment with a substantial number of patients (31%) developing metastatic disease, which led to a 31% overall survival at 5 years.ConclusionsAmong patients with local/regional recurrent HNSCC status-post radiation, surgery + Cs-131 demonstrated acceptable safety with compelling oncologic outcomes, as compared to historic control cohorts.Clinical Trial RegistrationClinicalTrials.gov, identifiers NCT02794675 and NCT02467738.

The treatment landscape for renal cell cancer (RCC) has evolved tremendously over the last two decades. Treatment algorithms have shifted from the highly toxic drugs with marginal benefit to better tolerated and more effective targeted therapy drugs. The latter include tyrosine kinase inhibitors, vascular endothelial growth factor inhibitors, MET inhibitors and, more recently, immunotherapy drugs alone and in various combinations. The majority of treatment algorithms for non-clear cell carcinoma have been based on extrapolating results from clear cell RCC trials and retrospective reviews. However, now that we understand that non-clear cell RCC is morphologically and clinically distinct from its clear cell counterpart, several collaborative clinical trials are underway for non-clear cell RCC. This review will delve into the historical aspects of treating non-clear cell RCC and the evolution of treatment paradigms over the last few decades with a focus on immunotherapy based trials.

Objectives To evaluate and categorize the survival benefit of tricyclic antidepressants (TCAs) in lung cancer patients based on systematic computational drug repositioning data. Methods Data were retrospectively extracted from the medical records of non-small cell lung cancer (NSCLC) patients from the University of Cincinnati Cancer Medical Center database. Patients receiving antidepressants during their course of anti-cancer treatment were compared with those without antidepressants. Data were analyzed using Kaplan–Meier survival curves with the log-rank test, and overall survival (OS) was calculated from the date of diagnosis until last follow-up or death. Results The median OS at 2 and 5 years for patients on antidepressants was 20.3 months (54.7% and 42%) vs 44.3 months (47.6% and 43.2%), which was not significant. The median OS for patients receiving TCAs, selective serotonin reuptake inhibitors, and other antidepressants was 3.17 months, 31.33 months, and 18.50 months, respectively. Conclusion We found no significant survival benefit for TCA use in combination with anti-cancer agents in NSCLC patients.

A 73 year old man presented to his primary care physician with sudden onset dysphagia to solids and liquids. He urgently completed a barium swallow study showing what was believed to be a coin. Endoscopic removal subsequently revealed it was a lithium battery. Consequences and management of lithium battery ingestion are discussed.