Introduction: There is growing recognition of immune related adverse events (irAEs) from immune checkpoint therapies being correlated with treatment outcomes in certain malignancies. There are currently limited data or consensus to guide management of irAEs with regards to treatment rechallenge. Methods: We conducted a retrospective analysis with an IRB-approved protocol of adult patients seen at the WVU Cancer Institute between 2011–2019 with a histopathologic diagnosis of active cancers and were treated with immune checkpoint inhibitors (ICI) therapy. Results: Demographics were similar between the ICI interrupted irAE groups within cancer types. Overall, out of 548 patients who received ICI reviewed, there were 133 cases of ≥1 irAE found of any grade. Being treated with anti-CTLA-4 inhibitor ICI was associated with lower risk of death compared to anti-PD-1 ICI. The overall survival difference observed for irAE positive patients, between rechallenged (37.8 months, reinitiated with/without interruption; 38.6 months, reinitiated after interruption) and interrupted/non-reinitiated (i.e., discontinued) groups (24.9 months) was not statistically significant, with a numerical trend favoring the former. Conclusions: Our exploratory study did not identify significantly different survival outcomes among the Appalachian West Virginia adult cancer patients treated with ICI who developed irAE and had treatment reinitiated after interruption, when compared with those not reinitiated.

Renal Clear Cell Carcinoma (RCC) comprises over 80% of renal malignancies in adults. Thyroid gland metastasis is rare in RCC. Few studies have described cases of RCC mistaken for benign arteriovenous malformation (AVM). To the best of our knowledge, an AVM arising from underlying RCC metastasis to the brain has not yet been reported. The current study presents a case of RCC metastasis to the thyroid gland, with an AVM identified to be a result of metastatic involvement in the brain. A 45-year-old African-American female presented with left-sided weakness, slurred speech, facial droop and seizure. The patient's medical history was notable for a diagnosis of RCC, 2010 American Joint Committee on Cancer Tumor-Node-Metastasis Stage 1B (T1B, N0, M0) grade III status post-right partial nephrectomy. Computed tomography (CT) imaging revealed a soft-tissue mass, suspected to be metastasis, in the left lobe of the thyroid, in addition to a 1.9 cm right intracranial mass in the parietal lobe. Positron emission tomography/computed tomography revealed a hypermetabolic area in the thyroid. Fine needle aspiration of the thyroid, and subsequent histopathological analysis, suggested a diagnosis of RCC metastasis. Subsequent immunohistochemical analysis of the thyroid tumor confirmed RCC metastasis. The patient also underwent a right partial craniotomy with resection of the intra-axial mass. Initial pathology was suggestive of an AVM. After several months, the patient was readmitted with headache, nausea and vomiting. Repeat imaging revealed recurrence of a 3.9 cm mass that was negative for AVM on biopsy; however, the immunostaining markers were positive for RCC. Recent literature suggests a link between AVMs and RCC as each exhibit highly vascular characteristics. RCC is a particularly vascular tumor that has been demonstrated to lead to the abnormal expression of various angiogenesis-promoting growth factors, including vascular endothelial growth factor. These angiogenic factors are vital to the pathophysiological pathway involved in the tumorigenesis and progression of RCC, and may explain the development of AVMs within these neoplasms, as demonstrated in the case presented in the current study.

No abstract

Background: Aspirin use lengthens survival in patients with colorectal cancer (CRC). We aimed to add to the evidence examining this relationship and to compare the survival benefit between aspirin started before CRC diagnosis with those started after CRC diagnosis. Methods:The study involved 173 consecutive patients who had a histopathologic diagnosis of colorectal carcinoma between 1996 and 2014. The electronic medical record was used to collect data on demographic characteristics (age, sex, and race), family history of cancer, use or non-use of aspirin before and after cancer diagnosis, cancer stage at diagnosis, and days from cancer diagnosis to death. Patients were divided into aspirin using and non-aspirin using groups.Results: Aspirin users (ASAU, n=90) were older than non-aspirin users (NASAU, n=83; 70.8±9.1 vs. 66.2±10.2 years; P=0.004). The two groups were similar in sex, race, and family history of cancer, but the non-users of aspirin were more likely to have stage III or stage IV CRC (NASAU =57.5%; ASAU =38.6%; P=0.014). Aspirin users survived more than twice the number of days than non-users (ASAU median =941 days; NASAU median =384 days; P=0.003). Patients who used aspirin only before their CRC diagnosis had a short survival period from diagnosis to death (median =149).Conclusions: Our findings support the relationship of aspirin use and duration of use with enhanced survival in patients with CRC. Physicians may want to recommend that patients at increased risk for CRC and those already diagnosed, but not yet on aspirin, start an aspirin regimen.

Introduction: Immunotherapy works by stimulating the immune system against cancer cells. Resistance to immunotherapy represents a significant challenge in the field of medical oncology. The mechanisms by which cancer cells evade immunotherapy are not well understood. Prior research suggested overexpression of prostaglandin E-2 (PGE-2) by cancer cells, which bind to EP-2 and EP-4 receptors on the tumor-specific cytotoxic T-lymphocytes (CTLs) and suppress their anticancer role. This immunosuppressive effect is involved in evading the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade of immunotherapy, which fuels cancer cell growth and recurrence. Studies found that combining PGE-2 blockade and a PD-1 signaling inhibitor helped promote the anticancer immunity cells. If confirmed in a clinical setting, the above in vitro findings could be of great clinical significance.Methods: Given that aspirin (ASA) blocks PGE-2 production, this work aimed to evaluate whether ASA use with immunotherapy results in better outcomes than immunotherapy alone. We performed a retrospective chart review of 500 non-small cell lung cancer (NSCLC) patients aged 21 years or older treated with PD-1 and/or PD-L1 directed immunotherapy at St. Luke's University Health Network between July 2015 and July 2021. Relevant patient, disease, and treatment-related variables were collected, including ASA use (≥ 81 mg daily) and the type of immunotherapy. Bivariate analyses were conducted to determine which variables to include in a multivariable model.The four primary outcomes included survival at 18-months, both after diagnosis and starting immunotherapy, achieving complete remission (CR), and having a progressive disease (PD), as defined by RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Secondary outcomes included therapyrelated toxicities and complications in the different treatment groups.Results: After bivariate analysis, no statistical significance was found for a difference in 18-month survival between ASA and non-ASA groups (50.3% vs 49.7%, p-value = 0.79). ASA with PD-L1 inhibitor showed a trend towards a higher likelihood of achieving CR [adjusted odds ratio (AOR) 1.85] with a p-value close to statistical significance (0.06). However, ASA with PD-L1 showed high statistical significance as an independent variable associated with a decreased likelihood of having PD (AOR 0.44, p < 0.001). These findings suggest that NSCLC patients receiving PD-L1 inhibitors could benefit more from daily ASA than patients treated with PD-1 inhibitors. Our study emphasizes using the Eastern Cooperative Oncology Group (ECOG) scoring of the performance status (PS) in NSCLC patients. Poorer PSwas associated with lower survival, decreased likelihood of CR, and more PD. Other variables associated with worse outcomes were advanced cancer stage at diagnosis and male gender. Low-PD-L1 expression in NSCLC was associated with an increased likelihood of survival; this could be of clinical significance, especially with previous studies su...