Background: Patients with lung cancers may have disproportionately severe coronavirus disease 2019 outcomes. Understanding the patient-specific and cancer-specific features that impact the severity of COVID-19 may inform optimal cancer care during this pandemic. Patients and methods: We examined consecutive patients with lung cancer and confirmed diagnosis of COVID-19 (n ¼ 102) at a single center from 12 March 2020 to 6 May 2020. Thresholds of severity were defined a priori as hospitalization, intensive care unit/intubation/do not intubate ([ICU/intubation/DNI] a composite metric of severe disease), or death. Recovery was defined as >14 days from COVID-19 test and >3 days since symptom resolution. Human leukocyte antigen (HLA) alleles were inferred from MSK-IMPACT (n ¼ 46) and compared with controls with lung cancer and no known non-COVID-19 (n ¼ 5166). Results: COVID-19 was severe in patients with lung cancer (62% hospitalized, 25% died). Although severe, COVID-19 accounted for a minority of overall lung cancer deaths during the pandemic (11% overall). Determinants of COVID-19 severity were largely patient-specific features, including smoking status and chronic obstructive pulmonary disease [odds ratio for severe COVID-19 2.9, 95% confidence interval 1.07e9.44 comparing the median (23.5 packyears) to never-smoker and 3.87, 95% confidence interval 1.35e9.68, respectively]. Cancer-specific features, including prior thoracic surgery/radiation and recent systemic therapies did not impact severity. Human leukocyte antigen supertypes were generally similar in mild or severe cases of COVID-19 compared with non-COVID-19 controls. Most patients recovered from COVID-19, including 25% patients initially requiring intubation. Among hospitalized patients, hydroxychloroquine did not improve COVID-19 outcomes. Conclusion: COVID-19 is associated with high burden of severity in patients with lung cancer. Patient-specific features, rather than cancer-specific features or treatments, are the greatest determinants of severity.
BACKGROUND. Extraskeletal myxoid chondrosarcoma (EMC) is a genetically distinct sarcoma with a propensity for local recurrence and metastasis despite an indolent course. To the authors' knowledge, there are limited data examining chemotherapy outcomes as a guide to therapeutic decisions for unresectable disease. METHODS. The clinical behavior and treatment responses of 87 patients with EMC who were seen at 2 institutions between 1975 and 2008 were examined. RESULTS. The median age of the patients at the time of diagnosis was 49.5 years, with a male‐to‐female ratio of 2:1. For patients presenting without metastases, 37% developed local recurrence (median time of 3.3 years) and 26% developed distal recurrence (median time of 3.2 years). Approximately 13% of patients presented with metastases. The 5‐year, 10‐year, and 15‐year overall survival rates were 82%, 65%, and 58%, respectively. Twenty‐one patients received 32 evaluable courses of chemotherapy. No significant radiologic or clinical responses were noted. The median time to disease progression while receiving chemotherapy was 5.2 months. The best physician‐assessed response to chemotherapy was stable disease for at least 6 months in 25% of patients, stable disease for <6 months in 41% of patients, and disease progression in 34% of patients. The estimated progression‐free survival rates at 3 months, 4 months, 6 months, and 9 months were 69%, 65%, 40%, and 26%, respectively. CONCLUSIONS. This retrospective review highlights the poor response rate to chemotherapy and emphasizes aggressive control of localized disease as the primary approach to management. Although there are biases inherent in retrospective analyses, these data provide a benchmark for time to disease progression for the study of new agents for the treatment of patients with this diagnosis. Cancer 2008. © 2008 American Cancer Society.
Objectives Small cell lung cancers (SCLCs) are characterized by aberrantly-methylated O6-methyl-guanine-DNA methyltransferase (MGMT). Epigenetic silencing of MGMT is associated with loss of MGMT activity and improved sensitivity to alkylating agents in glioblastomas. We have reported the activity of temozolomide, a non-classical alkylating agent, in patients with relapsed sensitive or refractory SCLCs, given at 75 mg/m2/day for 21 of 28 days. However, prolonged myelosuppression was noted. We therefore evaluated a 5-day dosing schedule of temozolomide and examined MGMT as a predictive biomarker for temozolomide treatment in SCLC. Materials and Methods Patients with sensitive or refractory SCLCs and progression after one or two prior chemotherapy regimens received temozolomide 200 mg/m2/day for 5 consecutive days in 28-day cycles. The primary endpoint was tolerability. We also assessed MGMT promoter methylation status by PCR and MGMT expression by immunohistochemistry in tumor specimens. Results Of 25 patients enrolled, 5 experienced grade 3 or 4 toxicity (anemia, thrombocytopenia, neutropenia, and constipation). The partial response rate was 12% [95% CI: 3–31%], with partial responses in 2 refractory patients. We were able to obtain tumor samples for more than half of patients for MGMT testing. Conclusion Temozolomide 200 mg/m2/day for 5 days in 28-day cycles is tolerable and active in patients with relapsed SCLCs. No treatment-limiting prolonged cytopenias were observed, making this our preferred schedule for further studies. Acquisition of archived biospecimens is feasible and necessary in order to continue evaluating the role of MGMT as a predictive biomarker in SCLCs.
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