Coronavirus disease-2019 (COVID-19) is a novel infectious disease, mainly affecting the respiratory tract, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). COVID-19 emerged in Wuhan, China, in December 2019 and rapidly escalated to become a global health crisis. Early reports on the prognosis of patients with cancer with COVID-19 were conflicting and limited. However, recent data have consistently shown trends of worse outcomes in patients with cancer, with increased rates of hospitalization and higher all-cause and COVID-19–related mortality. Several real-world studies from China and heavily affected regions in Italy noted higher mortality among patients with cancer and COVID-19 compared to the patients without cancer. Furthermore, single-institutional studies and national and international registries have shed more light on our understanding of the risk factors associated with a worse outcome in the population of patients with cancer and COVID-19.
The COVID-19 and Cancer Consortium (CCC19) was formed on March 15, 2020, to study the clinical characteristics and course of illness among patients with COVID-19 who have a current or past history of cancer in order to better understand the vulnerability of these patients to COVID-19. The consortium, which originated on Twitter, now comprises more than 120 participating institutions from a growing list of eligible countries, including the United States, Canada, Mexico, Argentina, and Colombia. Patient accrual to the registry began on March 17, 2020, and we now have more than 4,000 cases in the registry. The registry is built and maintained as an electronic REDCap database at Vanderbilt University Medical Center. Funding is provided by the American Cancer Society, National Institutes of Health, and the Hope Foundation for Cancer Research.
Our initial results were presented at the American Society of Clinical Oncology (ASCO) 2020 Virtual Scientific Meeting on May 28, 2020, with a simultaneous publication in The Lancet.1,2 These data included the first 928 lab-confirmed cases accrued through mid-April 2020. The median age was 66 years, and 50% were male. Breast (20%) and prostate (16%) cancers were most prevalent, and thoracic malignancies comprised 10% of the cohort; 43% of patients were on active anti-cancer treatment. At time of data analysis (May 7, 2020), 121 patients (13%) had died within 30 days of COVID-19 diagnosis, and 242 patients (26%) had met the composite outcome of death, severe illness requiring hospitalization, and/or mechanical ventilation. Multivariable analysis demonstrated that independent factors associated with increased 30-day mortality were age, male sex, former smoking, Eastern Cooperative Oncology Group (ECOG) performance status of 2 or greater, active progressing malignancy, and receipt of azithromycin plus hydroxychloroquine.
Our most recently updated analysis presented at the American Association of Cancer Research COVID-19 and Cancer Virtual meeting on July 21, 2020, included 2,749 patients with cancer and COVID-19.3 Overall 30-day all-cause mortality for the CCC19 cohort increased to 16% (433 patients) and approximately 60% of the patients (1,637 patients) required hospitalization. Twenty-nine percent of the patients (810 patients) had met the composite outcome of death, severe illness requiring hospitalization, and/or mechanical ventilation. These increases are presumably due to longer median follow-up, as opposed to a general worsening of COVID-19. Factors associated with an increased 30-day mortality were older age, male sex, race (non-Hispanic Black), current or former smoking, ECOG performance status of 1 or greater, and active cancer. However, none of the cancer therapies (cytotoxic chemotherapy, immunotherapy, targeted therapy, endocrine therapies, and radiation) were independently associated with an increased risk of 30-day all-cause mortality. While thyroid and breast cancer had the lowest mortality rates among all malignancies (3% and 8%, respectively), a striking 26% (61 of 237 patients) mortality rate was seen in the population with lung cancer. The consortium plans to undertake a lung cancer–specific analysis in the future.
Another global registry focused on thoracic malignancies, TERAVOLT (Thoracic Cancers International COVID-19 Collaboration), has provided more understanding of the patient- and cancer-specific risk factors in the population with lung cancer and COVID-19. Results from the first 428 patients in TERAVOLT were presented at the ASCO 2020 Virtual Scientific Symposium. More than 80% had NSCLC, and approximately 70% had stage IV disease 4. Similar to CCC19, the study showed remarkably high rates of hospitalization (78%) and an unexpectedly high overall mortality rate of 35%. Patient-related risk factors associated with an increased mortality included age older than 65 years, presence of comorbidities, and ECOG performance status of 1 or greater. Use of steroids (equivalent of prednisone > 10 mg/day) and anticoagulation prior to COVID-19 diagnosis correlated with increased risk of death. As opposed to immunotherapy or targeted therapies by themselves, prior administration of chemotherapy (alone or with immunotherapy) within 3 months of COVID-19 diagnosis was associated with increased risk of death. A later sub-analysis evaluated other rare thoracic malignancies (small cell, mesothelioma, thymic cancer, and carcinoid) from the TERAVOLT dataset.5 In this study, all-cause mortality was upwards of 40% in the small cell lung cancer and malignant mesothelioma populations, as compared to 35% in the overall TERAVOLT cohort. Another smaller study in patients with lung cancer (41 patients) showed no significant difference in severity of COVID-19 associated with immunotherapy exposure.6 A noteworthy component of this COVID-19–related mortality in patients with lung cancer is the association of a low rate of admission in the intensive care unit, which might reflect health system prioritization and permanent or transient management guidelines, but also these patients’ complex medical history, their resilience, and their preferences and choices.
Although patients with cancer overall experience worse outcomes with COVID-19 as compared to others, data from several studies report consistently increased risk of death in patients with lung cancer even compared to other cancers. It remains to be elucidated whether this might be due to a history of radiation or surgery, lung toxicity associated with systemic lung cancer drugs, presence of primary or metastatic disease in the lungs, impaired normal lung parenchyma, advanced age, impaired performance status, or a combination of all of these factors.
While it is critical to measure the impact of cancer-related factors on COVID-19 outcomes, it is crucial to understand the burden of this pandemic on cancer care delivery. As we navigate through this pandemic, we are learning the long-term effects of SARS-CoV-2 on lung cancer outcomes. Challenges in cancer care delivery during the pandemic have resulted in significant delays in screening, diagnosis, imaging, systemic therapy, surgery, and surveillance visits. Recommendations from the American Thoracic Society allow deferring lung cancer screening and modify follow-up for lung nodules due to the added risk of COVID-19 exposure and resource allocation. Expert thoracic oncology panels have laid out recommendations to guide physicians in the management of lung cancers. For early-stage lung cancers, the American College of Surgeons and Commission on Cancer have provided guidance on triaging decisions based on the prevalence of COVID-19, available resources within the hospital, and the risks to the patients if surgical care is restricted. The European Society for Radiology and Oncology and the American Society for Radiation Oncology have issued recommendations on adopting radiation therapy during the pandemic without compromising long-term prognosis. National and international medical oncology groups like ASCO, the National Comprehensive Cancer Network, and the European Society for Medical Oncology have laid out elaborate guidelines for lung cancer care by risk stratifying based on level of complexity of the disease, clinical condition, and stage of cancer.
As we adapt to emerging data describing risk factors for COVID-19 complications, we have to constantly balance the risk of potentially life-threatening infection in patients with lung cancer with the short- and long-term consequences of delaying cancer care. We encourage institutions to continue to approach lung cancer treatment strategies in an individualized, multidisciplinary approach in order to prevent the addition of a significant excess of lung cancer deaths to the dramatic direct consequences of the COVID-19 pandemic.
References:
1. Kuderer NM, Choueiri TK, Shah DP, et al. Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study. Lancet. 2020;395(10241):1907-1918.
2. Warner JL, Rubinstein S, Grivas P, et al. Clinical impact of COVID-19 on patients with cancer: Data from the COVID-19 and Cancer Consortium (CCC19). J Clin Oncol. 2020;38(18_suppl):LBA110-LBA110.
3. AACR COVID-19 and Cancer Virtual Meeting: The Distressing Intersection of the Pandemic and Noncommunicable Diseases – American Association for Cancer Research (AACR). https://www.aacr.org/professionals/blog/aacr-covid-19-and-cancer-virtua…. Accessed August 12, 2020.
4. Horn L, Whisenant JG, Torri V, et al. Thoracic Cancers International COVID-19 Collaboration (TERAVOLT): Impact of type of cancer therapy and COVID therapy on survival. J Clin Oncol. 2020;38(18_suppl):LBA111-LBA111.
5. Program | AACR Virtual Meeting: COVID-19 and Cancer | AACR Meetings. https://www.aacr.org/meeting/aacr-virtual-meeting-covid-19-and-cancer/p…. Accessed August 12, 2020.
6. Luo J, Rizvi H, Egger J V., Preeshagul IR, Wolchok JD, Hellmann MD. Impact of PD-1 Blockade on Severity of COVID-19 in Patients with Lung Cancers. Cancer Discov. 2020;10(8):1121-1129.
