|Year : 2020 | Volume
| Issue : 3 | Page : 171-176
Evaluating oncological outcomes of patients amidst the COVID-19 pandemic
Department of Surgical Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu, India
|Date of Submission||01-Aug-2020|
|Date of Decision||05-Aug-2020|
|Date of Acceptance||08-Aug-2020|
|Date of Web Publication||27-Oct-2020|
Professor, Cancer Institute (WIA), 38, Sardar Patel Road, Adyar, Chennai 600 036, Tamil Nadu
Source of Support: None, Conflict of Interest: None
The coronavirus disease 2019 (COVID-19) pandemic has caused and continues to cause a great deal of morbidity and mortality among patients worldwide. The unrelenting pandemic has raised important issues with regard to the need for rationing healthcare services in general and oncology care in particular, in the context of strained resources and crisis-handling capacity. The management outcomes of cancer patients amidst the COVID-19 pandemic are not well characterised, and we review the limited available evidences in this regard. These evidences seem to suggest that it is wise to continue standard cancer treatments especially so for patients who test negative for COVID-19 amidst the pandemic, unless there is a compelling reason to consider a deviation. The final decision for starting, delaying or deviating from the standard protocols should ideally be made as a part of a shared multidisciplinary decision-making process and should further be individualised for each patient. Although the exact magnitude of the disruptions on cancer care is difficult to quantify as yet, the oncology community will have to study and introspect on the collateral damage caused by the COVID-19 pandemic on the long-term outcomes of cancer patients. The world has witnessed many prior pandemics and humanity has survived them all and has eventually emerged stronger, and we hope that this time it will be no different. The need of the hour is for the scientific community to rise, learn from this unprecedented experience and align together towards creating a stronger and safer future.
Keywords: COVID-19, oncological outcomes, pandemic, SARS-CoV-2
|How to cite this article:|
Krishnamurthy A. Evaluating oncological outcomes of patients amidst the COVID-19 pandemic. J Clin Sci Res 2020;9:171-6
| Introduction|| |
The coronavirus disease 2019 (COVID-19) pandemic has caused and continues to cause a great deal of morbidity and mortality among patients worldwide. The reorganisation of the clinical services in response to the pandemic has further resulted in significant disruptions in the delivery of healthcare services across specialities including the multidisciplinary oncology services. Many institutions worldwide have seen a significant decrease in the numbers of diagnostic and therapeutic oncological procedures performed during the course of the pandemic. Patients with cancers are believed to be more vulnerable to infections because of their age, comorbidities, immunosuppressed status and cancer treatments; they consequently represent a high-risk group in the COVID-19 pandemic.
The initial reports on the incidence of COVID-19 in cancer patients came from Wuhan, China, wherein 0.79% of the 1524 patients admitted with cancer had an infection with severe acute respiratory syndrome coronavirus 2 (SARS- CoV- 2)., The authors further noted that this rate was higher than the cumulative incidence as noted in the community (0.37%) served by the hospital. The authors, hypothesised that this observation was due to the effect of cancer treatment-induced immune suppression, although only 41.7% of the patients in their series received any cancer-directed treatments. A few other studies from China suggested that about 1%–2% of the patients with COVID-19 infection had cancer., On the other hand, a much higher rate of cancer was noted from similar studies reported from New York (6%) and from Lombardy, Italy (8%). Although the above data seem to suggest that cancer patients may have a higher risk of acquiring COVID-19 infection, they are biased by several confounding factors, mainly pertaining to the differences in the criteria for testing and also imbalances in age, gender and co-morbidities.
The initial studies from China also suggested that patients with cancer appeared to be at an increased risk of severe illness and mortality due to SARS-CoV-2, regardless of whether they had active cancer or not. As a fall-out of the above studies, oncologists were unsure of the ultimate benefit of their interventions, especially when it had to be weighed against the risk of introducing an inadvertent SARS-CoV-2 infection in their healthcare systems. There were a few guidelines developed by various oncology societies to aid the treating oncologist in making complex management decisions. However, considering that the COVID-19 pandemic is a new respiratory infection, the available evidences were predominantly based on expert consensus. The delivery of oncology care during the pandemic was hence considered challenging given the competing risks of death from cancer versus the risks of death from COVID-19. The clinical presentation and management outcomes of cancer patients amidst the COVID-19 pandemic are not well characterised, and we review the limited available evidences in this regard.
| Clinical Presentation and Need for Testing for Covid-19 Infection in Cancer Patients|| |
The clinical presentation of COVID-19 and cancer seems to be no different from an infected patient without cancer. The presentation of the COVID-19 infection can vary from asymptomatic, subclinical or mild flu-like symptoms to a very fulminant pneumonia, occasionally leading to multiorgan failure or death. The array of symptoms includes fever, cough, breathlessness, sore throat, anosmia and ageusia. It is important to note that, certain patients with cancer and more so patients on active cancer treatment can at times present with fever and symptoms of lower respiratory tract infections. These patients would need to be tested for COVID-19 on a priority basis At the same time, the treating oncologist should also evaluate for alternative causes of their symptoms, such as influenza, other causes of pneumonia, pulmonary progression and post-surgical or therapy-related pulmonary events. It is important for the treating oncologists to note that the chest tomography findings of COVID-19 pneumonia can at times overlap with the findings that are noted in cancer patients with metastatic lung disease.
There seems to be a great deal of variation in the recommendations for testing asymptomatic hospital inpatients for COVID-19 in the oncology setting. Many guidelines recommend testing all inpatients, especially those who are slated for non-emergency surgeries. The guidelines also specifically recommend for testing asymptomatic individuals prior to the initiation of immunosuppressive therapies such as cytotoxic chemotherapies, solid organ/stem cell transplantation and biological therapies. The decision for testing would finally be dictated by the availability of tests and more so on the hospital protocols based on the prevalence of the pandemic in that region.
| Approach to Patients Who Test Positive for Sars-Cov-2 Infection|| |
The management of cancer patients with COVID-19 infection would logically depend on it severity of the infection. There is a broad consensus to stop non-emergency surgeries and immunosuppressive cancer therapies for patients who test positive for COVID-19 infection. However, there are certain exceptions such as patients with certain haematological malignancies and patients on steroids for severe immune-related adverse events, and these situations merit additional considerations. Continuation of therapy is also recommended on a case-by-case basis for patients who are on oral non-immunosuppressive therapies such as hormonal therapies or drugs targeting activating mutations.
There are no universally accepted guidelines as to when cancer therapies can be safely restarted after recovery from a COVID-19 infection. The uncertainty stems from the implications of further suppressing the patient's immune system after a COVID-19 infection, and this must be in turn weighed against the biology of the cancer. The American Society of Clinical Oncology guidelines recommend that routine inpatient care for COVID-19-positive patients should be delayed for a minimum of 2 weeks from symptom onset. The guideline also suggests twice testing for COVID-19 infection, 24 hours apart after a symptom-free period of 3 days. The final decision for retesting/restarting treatment would ultimately rest on the clinical judgement of the oncology team as the case would merit apart from the hospital protocols. There is more uncertainty with regard to the management of patients who continue to test positive for COVID-19 infection even after 2 weeks of the initial infection.
| Oncological Outcomes Amidst the Covid-19 Pandemic|| |
The data from a few studies suggested that the likelihood of developing a severe illness from COVID-19 was higher among patients with cancer, particularly among patients who had haematologic malignancies, lung cancers and in patients with metastatic disease. In a study of 218 COVID-19-positive patients with cancer, a case fatality rate of 37%, 25% and 55% were noted for haematologic malignancies, solid tumours and in patients with lung cancers, respectively. A higher mortality rate was particularly noted in patients with older age and with multiple comorbidities necessitating a need for intensive care. When compared with a matched cohort of 1090 patients with COVID-19 infection but without cancer, the case fatality rate for cancer patients was twice to that of the non-cancer patients (28% vs. 14%). Despite these reports, it still remains uncertain if cancer patients other than those with haematologic malignancies or lung cancers are at an increased risk of adverse outcome from COVID-19, when the analysis is controlled for age and other comorbidities.,
Two subsequent single-institution studies from New York had reported on survival outcomes of patients with cancer. A study in 334 patients with cancer reported a mortality rate of 11%, while another study in 218 patients with cancer reported a very high case fatality rate of 28%, although the authors of the latter study acknowledged a bias towards reporting more severe cases.
A meta-analysis of 32 studies involving 46,499 patients addressing the survival outcomes of COVID-19 patients with cancer showed that the all-cause mortality was higher in patients with cancer with a relative risk of 1.66. The need for intensive care unit admission was also found to be more in patients with cancer (relative risk of 1.56). Another systematic review and meta-analysis from 26 studies involving 23,736 cancer patients drew similar conclusions
| Outcomes of Recent Cancer Treatment Amidst the Covid-19 Pandemic|| |
A meta-analysis, compiling the data of four studies from China, concluded that receiving cancer therapy within 2–4 weeks of developing a COVID-19 infection was associated with a 4-fold higher mortality as compared with not having received cancer therapies (odds ratio of 3.99). However, the largest of the studies (contributing to 80% of the data) included in the above meta-analysis was criticised for incomplete documentation. In yet another retrospective study in 423 cancer patients with COVID-19 infection, patients who were treated with immune checkpoint inhibitors had a 3-fold higher risk of severe illness and hospitalisation.
On the other hand, more recent data collected from two international collaborative groups concluded that recent cancer therapy did not increase the risk of mortality from COVID-19., The international COVID-19 and Cancer Consortium registry reported data on 928 patients with active or prior malignancy, with a COVID-19 infection. The study clearly showed that use of any form of cancer therapy i.e., cytotoxic or otherwise within a month of infection was not associated with higher 30-day mortality. The independent factors associated with higher 30-day mortality were old age, male sex, prior smoking status, presence of two or more comorbidities, Eastern Cooperative Oncology Group performance status of 2 or more and in patients with active cancer. Another study on similar lines from the United Kingdom Coronavirus Cancer Monitoring Project registry reported no detrimental effect of recent administration of chemotherapy in 800 patients with a diagnosis of active cancer and COVID-19 infections.
It must be noted that all the above studies should be interpreted with caution as they are largely retrospective with their inherent selection biases, given the fact that patients who were tested are generally symptomatic and that the threshold for testing was much lower in the hospital settings. In contrast to adults, the available limited data suggest that most paediatric cancer patients are not necessarily more vulnerable than other children to infection, or to severe morbidity resulting from SARS-CoV-2.
| Outcomes of Recent Cancer Surgery Amidst the Covid-19 Pandemic|| |
The outcomes from oncological surgeries have been reported in an observational study in 1128 patients who had a confirmed COVID-19 infection within a week prior or a month following cancer surgery. The reported 30-day mortality rates from this study were unusually high at 24%. The study further noted that post-operative pulmonary complications were noted in over half of the patients, and these patients had a very high mortality, in fact contributing to nearly 83% of all mortalities. The independent risk factors for mortality in this study were male sex, age 70 years or older, American Society of Anaesthesiologists Grades 3–5, major surgeries and surgery for cancer and emergency surgeries. The reported rates of adverse outcomes significantly exceeded those noted in most of the types of surgeries in the pre-COVID era. The study results suggested that the thresholds for surgery during the COVID-19 pandemic should be higher than those during the normal practice.
However, a subsequent study from a tertiary care centre in Mumbai, India, reported the short-term outcomes of surgically treated patients in the early phase of the pandemic. The study of 494 surgically treated patients reported no mortality and a major morbidity of 5.6%. This study included six patients who were incidentally discovered to be COVID-19 positive in the post-operative period. A similar observation was also observed from the author's centre (unpublished observations) with zero 30-day mortality from 157 major oncological surgeries done from March to June 2020, reaffirming the safety of performing oncological surgeries in carefully selected patients amidst the pandemic.
| General Considerations for Healthcare Workers, Patients and Caregivers|| |
The treating oncology centres would need to ensure that all healthcare workers, patients and their caregivers need to wear a face mask within the facility and also in the community. Further, the healthcare facilities should periodically appraise the healthcare workers about the various aspects including symptomatology of COVID-19, the various infection control protocols including proper and periodic handwashing, general and respiratory hygiene and social distancing.
| General Considerations for Oncologists Regarding Cancer Management|| |
The treating oncologists have over the months realised that the lower case fatality rate of COVID-19 meant that the benefits of treating selected cancer patients far outweighed the risks of dying from COVID-19 infection. A vast majority of the guidelines have suggested against postponing the treatment in patients negative for COVID-19 in the early stages of the pandemic, unless there were compelling reasons to consider a deviation., With regard to cancer surgeries, the larger understanding is that these surgeries cannot be considered 'elective' in many instances, and there are definite harms of delaying cancer surgeries. A similar recommendation is for radiation therapy wherein the recommendation is to proceed with therapy, especially in patients who are treated with a curative intent. Similarly, there is little evidence to support withholding chemotherapy or immunotherapy in otherwise-fit patients with cancer. A number of guidelines have, however, advised caution with the use of immunotherapeutic agents, as such therapies seem to exacerbate the clinical course of COVID-19, eventually leading to an adverse outcome. For patients receiving palliative therapies by any of the treatment modalities, the decision to continue such treatments would require a careful analysis of the inherent risks and benefits.
While oncologists should strive to provide standard-of-care therapies to all their patients throughout the pandemic, the reduced resources/access to the cancer care services may necessitate the use of alternate treatment strategies, particularly in institutions/regions with an inability to manage a surge in COVID-19 infections. The patients and oncologists would then be forced to make difficult decisions pertaining to the patients' risk assessment and the need for prioritising the intended oncological procedures., Delayed diagnosis and suboptimal cancer management during the pandemic can potentially result in cancer upstaging and compromised rates of cancer control, and this in turn can have a detrimental impact on the cancer-specific mortality. The decision for starting or delaying any cancer treatment should ideally be made as a part of a shared multidisciplinary decision-making process and should further be individualised for each patient. The treating oncologists must additionally be fully aware of the local and national protocols, knowing fully well that in case of a conflict, the local/national protocols supersede all the other standard oncology guidelines.
| The Impact of Covid-19 on Clinical Care and Cancer Research|| |
The COVID-19 pandemic has dramatically impacted the healthcare delivery worldwide with the development and increasing popularity of tele-consultations and telehealth. This new mode of consulting and communication has provided the oncology community a safe environment to interact with each other in multidisciplinary tumour boards as well as with the cancer patients, both in active treatment and cancer remission.
Cancer research has over the years transformed cancer care and has been providing eligible patients the much-needed additional treatment options with an ultimate hope of improving the survival outcomes. The COVID-19 pandemic has majorly disrupted new enrolments as well as ongoing participation in clinical trials worldwide, thereby posing a threat to the development of new agents or treatments. Many health regulatory bodies have provided guidance for sponsors and study sites so as to ensure patient safety, while maintaining the mandatory compliance and at the same time ensuring the study integrity., The research community needs to further the cause of clinical research with a renewed focus of developing new cancer drugs/therapies simultaneously with novel treatments for COVID-19 infection including the much-awaited vaccines. On the positive side, the COVID-19 pandemic has brought the various global scientific research teams to work together; it is indeed heartening to note that many such researchers have even adapted their work outside of their usual domain expertise in an attempt to fight the pandemic. Many researchers have also published their retrospective data on patterns of cancer care during the pandemic and their real-world experience could potentially aid the practicing oncologists make complex treatment decisions in the near future. This practice of global networking and the promise of open data-sharing platforms is a welcome step and must be strongly patronised.
In conclusion, the limited available evidences seem to suggest that it is wise to continue standard cancer treatments especially so for patients who test negative for COVID-19 amidst the pandemic unless there is a compelling reason to consider a deviation. The final decision for starting, delaying or deviating from the standard protocols should ideally be made as a part of a shared multidisciplinary decision-making process and should further be individualised for each patient. Although the exact magnitude of these disruptions on cancer care is difficult to quantify as yet, the oncology community will have to study and introspect on the collateral damage caused by the COVID-19 pandemic on the long-term outcomes of their cancer patients. The need of the hour is for the scientific community to rise, learn from this unprecedented experience and align together towards creating a stronger and safer future.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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