Eva Gordon

Introduction: The use of molecular profiling of tumor tissue to identify potential targeted therapies for cancer patients has been an increasingly useful tool in personalized medicine. Case presentation: Here, we present a case of a 60-year-old gentleman who was initially diagnosed in 2012 with stage II esophageal adenocarcinoma. Neoadjuvant chemoradiation followed by esophagectomy was shortly followed by recurrence in the liver and lung. Despite numerous local and systemic treatments over the subsequent three years, his disease persisted, and he was considering hospice care. Comprehensive genomic profiling revealed three somatic alterations in NOTCH1 in the tumor tissue. These mutations are rarely found in esophageal adenocarcinoma and are thus not common treatment targets that would have been considered for this patient in the absence of molecular profiling data. These molecular findings informed the patient’s enrollment in a phase 1 clinical trial with a pan-Notch signaling inhibitor targeting ă-secretase. After less than one year of treatment, the patient experienced a complete response; treatment was discontinued after two years, and he remained disease free for over 8 years before passing away from an unrelated cardiac event. Conclusion: This case highlights the clinical utility of comprehensive genomic profiling in identifying rare molecular findings that may inform clinical trial opportunities, even in heavily pretreated patients with limited therapeutic options. The functional significance of the NOTCH1 alterations and their relationship to the treatment response remain uncertain.

Infection with SARS-CoV-2 causes COVID-19 and has a well-established set of clinical symptoms. Olfactory and gustatory dysfunction are among the non-life threatening sequalae observed with both acute and chronic SARS-CoV-2 infection. This can lead to the loss of taste and smell and has been observed in large subsets of COVID-19 patients. Although non-life threatening, loss of taste and smell can contribute to decreased quality of life and prevent sufficient nutrient intake, which may negatively affect prognosis and recovery. Despite progress in the treatment of other symptoms caused by COVID-19, there are currently no standardized treatment protocols to mitigate loss of taste and smell caused by SARS-CoV-2 infection and most approaches thus far have evaluated sensory training and regimen-based treatment strategies independently. In this retrospective case series, we demonstrate the effectiveness of a comprehensive, combined treatment protocol for COVID-19-induced taste and smell dysfunction using olfactory and gustatory training in combination with vitamins and supplements, nasal irrigations, nerve stimulation exercises, and anti-inflammatory prophylaxis. Acutely infected patients with COVID-19-related loss of taste and smell were given a daily regimen of zinc, vitamin A, B-complex, vitamin D, and alpha lipoic acid in addition to saline nasal irrigation, fluticasone spray, nerve stimulation exercises, and repeated olfactory-gustatory training. Triamcinalone paste, theophylline, and prednisone were included daily with the observation of partial recovery. At two timepoints over approximately 20–37 days of treatment, taste and smell scores were quantified based on detection of agents included on each sensory training panel. Following this novel and comprehensive “Training ‘N’ Treatment” (TNT) protocol, every patient exhibited a complete recovery of taste and smell. Given the potential to provide relief to the many people with olfactory and gustatory dysfunction following SARS-CoV-2 infection, the effectiveness of this protocol warrants validation in a larger study.