The onset of the Covid-19 pandemic caused minor and major disruptions in cancer care, and the effect of those disruptions is slowly becoming apparent as preliminary data suggest that, compared to patients who have not received chemotherapy, “cytotoxic chemotherapy given within 4 weeks before confirmed Covid-19 is not a significant contributor to a more severe disease or a predictor of death,” report investigators with a large UK registry of cancer patients with Covid-19.
The UK Coronavirus Cancer Monitoring Project (UKCCMP) is the “first Covid-19 clinical registry that enables near real-time reports to frontline doctors about the effects of Covid-19 on patients with cancer,” Lee and colleagues explained. The UKCCMP was launched March 18, 2020, and within 5 weeks it had assembled a prospective database of 800 patients (449 men) from 55 cancer centers.
“The median time from identification of documented Covid-19 disease until study endpoints were met (death or discharge from hospital) was 5 days (range 0–38),” they wrote.
Among the cancer types included were:
- Female genital.
- Myeloma and other hematologic cancers.
- Urinary tract cancers.
Of the 800 patients in the database, 281 (35%) were receiving chemotherapy, 64 (8%) were receiving hormone therapy, 44 (6%) were receiving immunotherapy, 76 (10%) were receiving radiotherapy, and 72 (9%) were receiving targeted therapy.
Two hundred and twenty-six patients died since the database was launched, and those deaths were “principally attributable to Covid-19 in most patients (211 [93%]),” Lee and colleagues wrote.
The mortality rates based on the treatment were:
- Chemotherapy: 33%.
- Hormone therapy: 9%.
- Immunotherapy: 4%.
- Radiotherapy: 8%.
- Targeted therapy: 7%.
“Compared with the rest of the cancer cohort, patients who died were significantly older (median 73.0 years versus 66.0 years; P<0.001; more were male (146 [33%] of 449) than female (80 [20%] of 349),and those who died also displayed higher rates of comorbidities compared with those who did not, including cardiovascular disease (21% versus 11%; P<0.001)and hypertension (41% versus 27%; P<0.001). Patients who died were also more likely to present with symptoms of shortness of breath (57% versus 32%; P<0.001),” they wrote.
Of note, 272 patients received no cancer treatment and 41% of that group died. Why these patients received no cancer treatment is not explained in the paper from Lee and colleagues, but in an essay for The New England Journal of Medicine, Lisa Rosenbaum, MD, a cardiologist at Brigham and Women’s Hospital in Boston and a correspondent for NEJM, sought a perspective on the disruptive nature of cancer care in a pandemic through a series of interviews with oncologists.
Michael Grossbard, chief of hematology at New York University’s Langone Hospital, told her “Our practice of medicine has changed more in 1 week than in my previous 28 years combined.”
Rosenbaum wrote that cancer treatment, “which often involves immunosuppressive therapy, tumor resection, and inpatient treatment, has been disproportionately affected by Covid-19. Like other oncologists I spoke with, Grossbard, who primarily treats lymphoma, has been tasked with revising chemotherapy protocols to minimize both the frequency of chemotherapy visits and the degree of immunosuppression. For example, though patients with low-grade lymphoma typically receive maintenance therapy, it will not be recommended for now because it requires an office visit, worsens immunosuppression, and improves progression-free but not overall survival. Other protocol modifications have arisen because of cancellations of elective surgeries. For instance, some patients with solid tumors, such as breast and rectal cancers, are being offered systemic therapy before, rather than after, surgery.
“Many modifications may not affect long-term outcomes,” Rosenbaum continued. “Eric Winer, a breast oncologist at Dana-Farber Cancer Institute, believes, for instance, that giving antihormonal therapy to women with hormone-receptor–positive breast tumors and delaying surgery probably won’t alter overall survival, though this approach hasn’t been formally tested in Stage I disease. But even when there’s greater uncertainty about treatment modifications, Winer has been impressed by many patients’ graceful acceptance.”
Rosenbaum added that suspending other aspects of care “will have graver consequences. David Ryan, chief of oncology at Massachusetts General Hospital (MGH), told me that three patient groups worry him most. The first are the subgroup of patients with lymphoma for whom CAR-T therapy is potentially curative. More than half these patients receive therapy in clinical trials, many of which have been paused amid society-wide shutdowns; even if enrollment could continue, there’s concern about the need for ICU care in a resource-constrained system. A related concern is for patients requiring bone marrow transplants, given their high risk of infection and potential need for ICU care.
“Finally, and most wrenching to Ryan, are patients with refractory tumors who are nearing the end of life, but for whom an experimental targeted therapy may hold promise; Ryan would otherwise offer these patients enrollment in an early-phase trial,” she wrote. “One recent analysis suggests that such enrollment is associated with clinical benefit in nearly 20% of patients, and participation allows patients to have some hope in their dying days and to feel like they’re ’giving back’ to the scientific community.”
Lee and colleagues echoed the concerns raised in Rosenbaum’s essay, noting that the “disruption from the pandemic to normal oncological care has been huge for several reasons. First, cancer clinicians and the rest of the cancer team are under unprecedented pressures. These pressures include increasing concern from patients about their perceived vulnerability, cancelled cancer operations, a substantial drive to do telemedicine rather than face-to-face consultations, and a high degree of absence from work across the cancer team due to personal illness and self-isolation. Second, many oncologists are being redeployed to general or acute medicine roles to support the many Covid-19 admissions requiring intensive medical support and input.” Against that reality, Lee and colleagues designed UKCCMP as a public health surveillance registry “to answer important questions about the interaction of cancer, cancer treatments, and Covid-19, and to support rapid clinical decision making,” they wrote.
But there are a number of limitations: UKCCMP is dependent upon the testing policy in the U.K., which the authors said “is less permissive that that of other nations, and also relies on RT-PCR, which has a well described false-negative result. The project might therefore under-report total Covid-19 cases in patients with cancer, particularly those with no mild symptoms who did not require treatment at or present to healthcare centers.”
Nonetheless, Lee and colleagues concluded that UKCCMP numbers will grow and, as they grow, they may provide answers to nuanced questions, such as “the differential effects of various anticancer treatments on different components of the immune system (neutrophils, cytotoxic T cells, regulatory T cells, and macrophages) and how these factors will interplay with the risk of contracting SARS-CoV-2 infection, or with the possibility of severe Covid-19 disease sequelae such as the cytokine storm.”
- Data from the UK Coronavirus Cancer Monitoring Project study suggest recent chemotherapy use in patients with cancer before severe acute respiratory syndrome coronavirus 2 infection was not significantly associated with increased mortality.
- Be aware that results of this analysis suggest that Covid-19 mortality in cancer patients is “principally driven by advancing age and the presence of other non-cancer comorbidities.”
Peggy Peck, Editor-in-Chief, BreakingMED™
The study was funded by University of Birmingham and the University of Oxford.
Lee had no disclosures.
Rosenbaum is a cardiologist at Brigham and Women’s Hospital, an Instructor at Harvard Medical School, and a national correspondent for the Journal.
Cat ID: 120
Topic ID: 78,120,730,933,308,358,120,24,468,692,935,190,926,192,927,151,928,195,929,925,934