Oncolytic viruses represent a novel drug class in which native or modified viruses mediate tumor regression through selective replication within and lysis of tumor cells as well as induction of systemic antitumor immunity capable of eradicating tumor at distant, uninjected sites. Talimogene laherparepvec (TVEC) is a type I herpes simplex virus genetically modified to preferentially replicate in tumor cells, enhance antigen loading of MHC class I molecules and express granulocyte-macrophage colony-stimulating factor to increase tumor-antigen presentation by dendritic cells. It is presently the only oncolytic virus approved by the FDA with an indication for advanced melanoma based upon improved durable response rate in a randomized, phase III trial. Clinical trials are underway in melanoma investigating TVEC as neoadjuvant monotherapy and in combination with checkpoint inhibitors for unresectable disease as well as in an array of other malignancies. It is appropriate to review TVEC's biology mechanism of action, clinical indication and future directions as a prototype of the burgeoning class of oncolytic viruses.

BackgroundSevere myocarditis associated with electrical conduction abnormalities and occasionally heart failure has been well documented following treatment with immune checkpoint blockade with an estimated incidence of less than 1%. However, the incidence, early detection, and management of less severe immune-related myocarditis are unknown since most immunotherapy trials have not included routine cardiac monitoring. Herein, we provide the first description of subclinical or smoldering myocarditis with minimal signs and symptoms following immune checkpoint blockade with a single dose of ipilimumab and nivolumab.Case presentationOur patient was diagnosed with immune checkpoint blockade-induced myocarditis based upon an acute rise in serum cardiac troponin I beginning 2 weeks after the initial dose of ipilimumab/nivolumab consistent with the reported median onset of clinical myocarditis at 17 days, as well as a lack of other causes despite extensive cardiac evaluation. The patient initially presented with intractable nausea with no known gastrointestinal etiology. High dose glucocorticoid therapy led to rapid resolution of nausea and a four-fold decrease in troponin I over 4 days. Serum troponin I spiked again following a steroid taper to 13 times the upper limit of normal with endomyocardial biopsy revealing collagen fibrosis and lymphocytic inflammation predominantly comprised of CD8+ T cells consistent with chronic smoldering myocarditis. Serum anti-striated muscle antibodies were also detected with no evidence of rhabdomyolysis. Serum cardiac troponin I levels as an indicator of ongoing myocyte damage gradually improved with chronic prednisone at 10 mg daily. Late addition of intravenous immunoglobulin was associated with rapid normalization of creatine kinase-myocardial band.ConclusionsThis case demonstrates that subclinical, smoldering myocarditis may occur following immune checkpoint blockade, with evidence of both humoral and cell-mediated immunity responsive to corticosteroid therapy. This experience supports early monitoring for myocarditis with serial electrocardiograms and serum troponin I determinations in large, prospective cohorts of patients receiving combination immune checkpoint blockade as early detection and initiation of immunosuppression may forestall fulminant presentation of this disease and limit myocardial damage.

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Immune checkpoint blockade (CPB) utilizing such agents as ipilimumab, nivolumab, or pembrolizumab has revolutionized melanoma therapy and has seen continued utilization in numerous other malignancies in recent years. However, these agents come at the price of inflammatory immune-related adverse events. Despite the increasing recognition of biochemical thyroid dysfunction associated with CPB, information regarding potential imaging findings is sparse. We describe the first 2 cases of acute thyroiditis following CPB presenting as diffuse thyromegaly documented by computed tomography, ultrasound, and iodine uptake imaging. Given the rise in the use of CPB, it is important for radiologists to recognize potential imaging manifestations of therapy immune-related adverse events to avoid erroneous diagnosis and to prompt the biochemical investigation of thyroid function.

Ipilimumab and nivolumab for melanoma induced smoldering myocarditis remitting with steroids. Rechallenge with nivolumab produced steroid-refractory myocarditis confirmed by electron microscopy. Tacrolimus and mycophenolate transiently reduced inflammation, but antithymocyte globulin induced remission. Cardiomyopathy with fatty infiltration ensued, but the patient succumbed to rampant melanoma progression after lymphocyte depletion. ( Level of Difficulty: Advanced. )

Purpose Although previous reports addressed the differences in marginal reflex distance 1 (MRD-1) measurements based on various techniques of levator advancement, eyelid crease measurements have not been studied as markers in perioperative planning. In addition to possible benefits in optimal results for improvement of visual field defects and functional impairment, recent work has suggested that eyelid crease is important in the perception of attractiveness. Therefore, the aims of this study were to determine the change in eyelid crease measurements in levator advancement and to further expand on numerical correlation of levator advancement in preoperative planning to avoid overcorrection or undercorrection. Methods The authors performed a retrospective analysis of preoperative and postoperative eye measurements in patients who underwent levator advancement for ptosis between August 2016 and April 2019. This study included 13 patients, all of whom had recorded preoperative and postoperative measurements of MRD-1, whereas 8 of 13 patients had additional preoperative and postoperative measurements of the mid pupil to crease and lateral limbus to crease at the level of mid pupil. Results All patients had increased in MRD-1, mid pupil to crease, and lateral limbus to crease measurements postoperatively. The average advancement of 4.8 mm led to an elevation of MRD-1 to 2.6 mm (n = 25) and an improvement in mid pupil to crease distance of 1.9 mm (n = 15) and lateral limbus to crease distance of 2.6 mm (n = 15). No cases of undercorrection or overcorrection were found. All patients reported satisfaction with the results, including improvement in function and quality of life. No infections, hematomas, or other complications were noted postoperatively in any of the patients. Conclusions Marginal reflex distance 1 is a consistently reliable planning tool in preoperative assessment of levator advancement, with beneficial patient outcomes including improvement of visual field defects caused by ptosis and satisfaction with cosmetic results. This study is the first to report use of crease measurements (mid pupil to crease and lateral limbus to crease), which may provide additional understanding to the aesthetic value of to the levator advancement.

12036 Background: Older adults share a growing burden of cancer morbidity and mortality. The presence of comorbid medical conditions and polypharmacy may present significant challenges to cancer management for older adults. Although geriatric assessment (GA) is recommended to personalize treatment for older adults with cancer, it remains underutilized in routine oncology practice, and how best to measure comorbidity and polypharmacy remain unknown. The Comorbidity Polypharmacy Score (CPS), which is the sum of the number of comorbid medical conditions and medications for a patient, has been validated in other medical fields. Here we review the association of CPS with key outcomes among older adults with gastrointestinal (GI) malignancy. Methods: The Cancer and Aging Resilience Evaluation (CARE) tool is a brief, patient-completed GA developed for older adults with cancer at the University of Alabama at Birmingham (UAB). For patients enrolled in the CARE registry, diagnosed with a new GI malignancy between September 2017 and April 2021, we calculated a CPS based upon the number of patient-reported medical comorbid conditions and daily medications. Patients were separated into two groups, those with CPS ≥ 15, or high-risk, and those with CPS < 15. Multivariable analyses were adjusted for age, sex, race, cancer type, and cancer stage, and were performed to examine the potential association between high-risk CPS and falls, functional limitations, frailty, and mortality. Results: 548 patients were included in this study with a mean age of 69.7 years; 44.9% female and 23.9% Black. Common GI malignancies included colorectal (30.8%), pancreatic (25.5%), hepatobiliary (17.7%), and gastroesophageal (10.8%). Patients with CPS ≥ 15 were more likely to report falls (adjusted odds ratio [aOR] 3.39, 95% CI 1.91-6.02), dependence in activities of daily living (ADL) (aOR 3.07, 95% CI 1.67-5.66) and instrumental ADL (aOR 3.81, 95% CI 2.02-7.20), and have frailty (aOR 5.17, 95% CI 2.84-9.39). There was not a statistically significant association with either six-month or twelve-month survival. Conclusions: CPS was associated with falls, functional limitations, and frailty, but not survival, among older adults with GI malignancies. This association highlights the potential role of CPS as an efficient screening tool for older adults with cancer who would benefit from more comprehensive comorbidity and medication review.