Impact of COVID-19 on cancer services and patients’ outcomes: a retrospective single-center study

Introduction

The impact of coronavirus disease 2019 (COVID-19) on cancer patients has been an unknown entity with little knowledge that cancer patients overwhelmingly represent a potentially high-risk group. There is still a lack of data on cancer patients with COVID-19 and systemic fungal infections (1). The pandemic has impacted healthcare systems worldwide, disrupting usual care in many healthcare facilities, putting vulnerable cancer patients at significant risk. Despite a multi-pronged approach to preventing the spread, including lockdowns, social distancing, hand hygiene and masks, large sections of the population have been affected in almost all countries. The severity of the spread and complications varied from country to country. Within a year, many countries had already experienced a second wave. The understanding of the behavior of this novel virus was very vague, and research work was being carried out in a rushed way worldwide to find out the mode of spread in order to develop strategies for its prevention, including possible vaccines and curative treatment (2-6).

Whether cancer patients would do worse was not known to us, although the common belief was that they were high risk group considering the low immunity. It was assumed that the people with comorbidities will have worse outcomes. It was important to know for oncology centers about the actual risks of cancer patients of their susceptibility to infections and developing complications. Here, we present the first comprehensive one-year study among cancer patients affected with COVID-19 in Indian sub-continent. We present this article in accordance with the STROBE reporting checklist (available at https://atm.amegroups.com/article/view/10.21037/atm-22-5876/rc).

Methods

The primary objective was to find out the impact of COVID-19 on cancer services and cancer patients to determine the severity, morbidity and mortality with survival outcome. Secondary objectives were to find out the type of cancer affected most by COVID-19, the most common age group and gender. We also aimed to ascertain the correlation in cancer patients with other pre-existing co-morbidities and to determine the delay in treatment of cancer care and complications—if any—from cancer treatment following COVID-19 infection.

Study design and participants

We conducted a retrospective, observational cohort study at our Comprehensive Cancer Institute in Eastern India, which caters to approximately 60,000 patients affected with cancer every year. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Ethics Committee of the Saroj Gupta Cancer Centre and Research Institute in Kolkata, India (IEC SGCCRI REF No. 23/04/2021/NON-REG/BS/07), and the requirement for individual consent was waived. That decision was made given that the research could not be carried out practicably without the waiver, and equally the waiver would not adversely affect the rights and welfare of the subjects.

Data collection and analysis

After clearance from the Institutional Ethics Committee (IEC), we accessed electronic health records of all the cancer patients affected by COVID-19 from 1^st April 2020 to 31^st March 2021. Our data collection included new and follow-up cases during the pandemic and its preceding year, total number of reverse transcription polymerase chain reaction (RT-PCR) tests performed, total number of positive cases and a detailed demographic profile of all positive cancer patients which included the age and sex of the patient, diagnosis of cancer with the cancer site, stage and pre-existing co-morbidities. We also looked into the symptomatology at presentation, treatment modalities for COVID-19 (oxygen requirement, escalation to critical care, ventilation), time to negativity and mortality in cancer patients affected with COVID-19.

Statistical analysis

Associations between categorical data were tested using Chi-squared test. All tests were conducted with the two-sided 0.05 level with no adjustments for multiple comparisons. We assessed all study variables to analyze correlations with mortality using logistic regression. Also, the correlation of delay in treatment with other variables were analysed with linear regression. All analyses were performed using Python 3.0.

Results

Cases

The total annual cases was found to be 47,564 during the period of 2019–2020. This included 9,484 new registered cases and 38,080 follow-up cases, whereas the average annual cases during the pandemic year included 6,444 new registered cases and 16,848 follow-up cases with the total cases adding up to 23,292. Therefore, the reduction of overall cases was by 50.49%, of which the follow-up cases were reduced by 54.25% and the new cases by 37.17% (Table 1).

The follow-up cases who were under surveillance included patients in the follow-up category of cancer services. Those undergoing treatment, i.e., chemotherapy or radiotherapy were included in the study cohort where complete analysis and profiling was done (n=395).

Test and infectivity rate

From April 2020 to March 2021, a total of 5,401 RT-PCR tests were performed to detect COVID-19. The total number of positive cases was 395 out of 5,401 (7.31%), of which complete medical records were available for 310 patients.

Age and gender

Among the total 310 COVID-19 positive cancer patients, 142 (45.8%) were male and 168 (54.2%) were female (P=0.514 on univariate analysis with respect to mortality) (Table 2). The highest number of positive cases was recorded in the 51–60 age group, which was 74 (23.87%), followed by those over 60 (n=67, 21.61%) who did have the highest mortality rate. The lowest incidence was found in the second decade age group (n=17, 5.48%). The oldest positive patient was 87 years old and the youngest 2 years old, with the mean age of the study population being 48 years.

Diagnosis (including type of cancer in positive patients)

Among 310 COVID-19 positive cancer patients, the highest number of incidences were found in hematological malignancies (n=63, 20.32%), followed by gastrointestinal (GI) and hepato-pancreato-biliary (HPB) cancers (n=57, 18.39%). In univariate analysis, the P value was 0.000178, while multiple logistic regression gave a P value <0.0001 (Figure 1).

Figure 1 Distribution and incidence of COVID-19 among various types of cancer patients (A) and mortality caused in each of the groups (B). GI, gastrointestinal; HPB, hepato-pancreato-biliary; BR, breast; GO, gynecological; HN, head and neck; HT, hematology; RT, radiation oncology; COVID-19, coronavirus disease 2019.

Comorbidities

One hundred and seventy-seven out of 310 patients (57.10%) infected with COVID-19, had pre-existing comorbidities, such as hypertension (n=81, 26.13%; P=0.0028) and diabetes (n=47, 15.16%; P=0.0927) and have been on chemotherapy (n=73, 23.55%; P=0.3098). The remaining 42.90% (n=133) had no comorbidities.

Symptoms at presentation

Two hundred and sixty-three patients (84.84%) were asymptomatic, 28 patients (9.03%) had mild to moderate symptoms, while 19 patients (6.13%) developed severe symptoms including shortness of breath requiring ventilator support (P=0.0016).

Treatment for cancer

Compared to the previous year, there was a 53.05% reduction in surgery, 48.27% in radiotherapy and 53.92% in chemotherapy (Table 1). Home care was recommended for most palliative care patients.

Treatment done for COVID-19 infection

The modalities of COVID-19 management recommended by our hospital were based on the symptoms. Two hundred sixty-three patients (84.84%) were asymptomatic. Overall, 171 patients (55.16%) were primarily advised to self-isolate at home (P<0.0001), while the remaining 139 patients (44.84%) were all hospitalized because of cancer severity or COVID-19 along with comorbidities were hospitalized.

Delay in treatment time

Time to negativity on repeat RT-PCR testing was mostly within 4 weeks, although a significant number remained positive at 6 weeks. The mean delay in treatment was 5 weeks for surgery and radiotherapy and 6 weeks for chemotherapy.

Mode of treatment following negative report and outcome

After recovering from COVID-19 infection, 70 patients underwent active cancer treatment; 21 patients (6.77%) underwent surgery, 26 patients (8.39%) received chemotherapy, 13 patients (4.19%) received radiotherapy, while 2.65% of patients received palliative care at the end of life. In addition, 48 patients (15.48%) were undergoing chemotherapy as of the reporting date. The consumption of narcotic analgesics has been reduced by 36%.

Mortality

The total number of deaths among COVID-19 positive cancer patients was 64 (20.65%), with the highest mortality rate found in the age group over 60 years (n=18, 28.1%). GI and HPB malignancies accounted for the highest number of deaths (n=21, 32.8%), followed by hemato-oncologic malignancies (n=18, 28.1%). No major mortality and significant morbidity were observed in patients undergoing definitive anticancer treatment after COVID-19 (Figure 1).

On univariate analysis, age over 65 years (P=0.034), type of malignancy (P=0.000178), hypertension (P=0.0028), symptoms of COVID-19 infection (P=0.0016), treatment location and oxygen/intervention (P<0.0001) proved statistically significant for mortality from COVID-19 infection. However, multiple logistic regression revealed only cancer type (P<0.001) and oxygen/intervention were statistically significant for death due to COVID-19 infection. Multivariate analysis of treatment delay for COVID-19 infection showed that oxygen/intervention and chemotherapy were statistically significant factors (P<0.05) (Table 2).

Discussion

In this single-center retrospective cohort study, we analyzed the cohort of cancer patients affected by COVID-19, mainly during the first wave of the pandemic, when the majority of the population was unvaccinated. COVID-19 has spread in low- and middle-income countries and particularly India due to limited resources, poor infrastructure, lack of healthcare providers and organized care teams, lack of medical supplies and personal protective equipment and in -equal access to technology (7-10). The turnover of patients in the hospitals was greatly reduced during the lockdown because they could not use public transport, many had lost their livelihoods, several cancer hospitals became COVID-19 hospitals and mainly because of the fear of contagion. In fact, this delay in screening and diagnosing cancer has severely impacted the outcome in many countries (11). In a pan-Indian study by Ranganathan et al., involving the National Cancer Grid of India, the experience was similar in 283 cancer hospitals across the country (12). Many centres used telemedicine to advise their patients, especially to those who have already been treated, and to save them the trip to the hospital with the resulting risk of infection (13-16).

In our study, the overall frequency in the outpatient clinic (both new and recurrent cases) was reduced to 50.49% compared to the previous year, which mainly affects the recurrent cases. This means that although the newly diagnosed cancer patients decreased by 37.17%, they still managed to get to the hospital, while the follow-up cases, which decreased by 54.25%, went to teleconsultation and preferred to stay at home and only when clinically indicated were presented. The average stages of presentation were even later compared to the previous year. The experience was similar in most other studies (7-9). Because oncology care involves multiple hospital visits, patient infection rates tend to be higher. Another reason could be immunosuppression in cancer patients. A study by the Rajiv Gandhi Cancer Institute in Delhi has shown an incidence of COVID-19 in cancer patients of 6% compared to the national average of 0.32% (17). However, tests were only carried out there in patients with COVID-19 symptoms or with radiological changes in the chest. The incidence was 3 times higher in cancer patients compared to the general population, as shown in studies from Brazil and the US, and 15 times higher in a study that included all patients with active cancer and was presented to the network of cancer centers, which have been included in the UK Coronavirus Cancer Surveillance Project (UKCCMP) (18). In our study, it was 7.3% (23 times higher). Aside from the fact that this immunocompromised group has multiple hospital visits, another major reason for the higher positivity rate in most cancer hospitals like ours is that these patients are screened with RT-PCR testing prior to any invasive procedure (biopsies, endoscopies, surgeries), or long-term chemotherapy, while testing rates are much lower in the general population. Many of the cancer patients are asymptomatic as in the general population. In our series, 84.8% were asymptomatic, while 9.03% had mild symptoms and 6.12% had severe symptoms requiring admission to intensive care units, most of whom succumbed.

Cancer management guidelines during the COVID-19 pandemic have been adopted by various societies around the world such as the Surgical Society of Oncology (SSO) in the US, the National Health Service (NHS) in the UK, the European Society of Medical Oncology (ESMO) and the Indian Association of Surgical Oncology (IASO) to reduce the likelihood of infection and the development of complications (19). Non-emergency surgeries were deferred when there was an option for neoadjuvant therapy, learning from China, which reported a 25% mortality rate from chest complications in the postoperative period in the early stages of the pandemic. Death rates from COVID-19 are also generally much higher than predicted in cancer patients. A study from New York showed an overall mortality of 25% with highest fatality in lung and pancreatic cancers (55%) followed by hematological malignancies (37%), the least being in patients with breast cancer (14%) (20). The experience was similar in the UK, China and Italy (21-25). The majority of these patients had multiple comorbidities with a mean Eastern Cooperative Oncology Group (ECOG) score of 2 or greater. Cancer-related inflammation and the associated prothrombotic status of uncontrolled solid or hematological cancer growth could be considered responsible for the poor prognosis in hospitalized COVID-19 patients (13,26). It should be noted that cancer patients often coexist with comorbidities such as diabetes, hypertension, coronary artery disease, chronic kidney disease, which can further weaken the immune response and increase the risk of death from COVID-19 (27,28).

In our study, the highest incidence of COVID-19 infection was found in patients with hematological malignancies (20.32%), followed by GI and HPB malignancies (18.39%). The mortality in these cancer patients was 20.65% given their advanced type of malignancies and the severity of COVID-19 infection with or without comorbidities. The highest mortality was observed in patients with GI and HPB, followed by hematological malignancies (20.3% and 18.39%, respectively). With regard to the direct impact, our entire cohort included patients (n=395) with cancer, either newly diagnosed or previously known, who were affected due to COVID-19. Therefore, the impact of factors influencing variables like mortality or type of cancer have been analyzed here. Considering the indirect impact, the delay of cancer services was due to the general unavailability of medical services for investigations. Some of the external factors like government induced administrative lockdowns or lack of availability of adequate public transport led to this delay as well. Also, cancer patients harbouring COVID were treated in designated COVID centres. This throws light on the outcomes of the entire spectrum of cancer services affected by the pandemic between April 2020 to March 2021. The effects of the COVID-19 pandemic will have long-lasting repercussions in almost every aspect of oncology care. The National Cancer Institute (NCI) projected that there will be more than 10,000 cancer-related deaths over the next decade as a result of missed screenings, delays in diagnosis, and a reduction in oncology care due to the COVID-19 pandemic (29). As the pandemic evolves, we are gaining more knowledge that will improve our understanding of both the disease, i.e., COVID-19 as well as its impact on cancer. It will likely lead to major changes in healthcare, including oncology, which will involve greater remote care closer to home and greater use of technology in the delivery, research, education and corporate governance related to cancer care.

Conclusions

The pandemic led to a widespread decline in oncology services worldwide. Similar results were found in our study, where the overall percentage of services was reduced by more than 50%. The worst result among these was a 60.84% reduction in detection of new malignancies, resulting in patients emerging with late-stage malignancies after the first wave of the pandemic. As predicted, the most commonly affected age group was in the sixth decade, while the least affected was in the second decade. Delays in cancer treatment have also been shown to play an important role in the poor prognosis of cancer patients. Although the majority of our patients were asymptomatic, in these cases infection was only detected during routine testing before each procedure. Both conservative and interventional treatment modalities were used for the symptomatic patients. The incidence of COVID-19 infection was highest in hematological malignancies (20.3%), followed by GI and HPB (18.39%), the latter being responsible for the highest mortality. This suggests that while cancer patients are at a higher risk and more susceptible to infection with COVID-19 than the general population, there is a need to be more aware of the specific type of malignancies and to facilitate the necessary preventive measures for these patients to avoid them prevent any subsequent mortality.

Acknowledgments

We sincerely acknowledge the help from our Medical Records Department, Public Relation Officers, surgical oncology in charge—Dr. Saradindu Ghosh, research in charge—Dr. Samir Bhattacharya and medical oncology and palliative care in charge—Dr. Rakesh Roy for their support in obtaining the data of our COVID patients.

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://atm.amegroups.com/article/view/10.21037/atm-22-5876/rc

Data Sharing Statement: Available at https://atm.amegroups.com/article/view/10.21037/atm-22-5876/dss

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-5876/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Ethics Committee of the Saroj Gupta Cancer Centre and Research Institute in Kolkata, India (IEC SGCCRI REF No. 23/04/2021/NON-REG/BS/07), and the requirement for individual consent was waived. That decision was made given that the research could not be carried out practicably without the waiver, and equally the waiver would not adversely affect the rights and welfare of the subjects.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Mahajan I, Ghose A, Gupta D, et al. COVID-19, Mucormycosis and Cancer: The Triple Threat-Hypothesis or Reality? J Pers Med 2022;12:1119. [Crossref] [PubMed]
2. Jazieh AR, Coutinho AK, Bensalem AA, et al. Impact of the COVID-19 Pandemic on Oncologists: Results of an International Study. JCO Glob Oncol 2021;7:242-52. [Crossref] [PubMed]
3. Desai S, Gupta A. IASO COVID-19 Guidelines (Updated on 9th April 2020). Indian J Surg Oncol 2020;11:171-4. [Crossref] [PubMed]
4. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424. [Crossref] [PubMed]
5. Revythis A, Shah S, Enyioma S, et al. The Experience of a Single NHS England Trust on the Impact of the COVID-19 Pandemic on Junior and Middle-Grade Doctors: What Is Next? Int J Environ Res Public Health 2021;18:10413. [Crossref] [PubMed]
6. Sharma E, Revinipati S, Bhandari S, et al. Efficacy and Safety of COVID-19 Vaccines-An Update. Diseases 2022;10:112. [Crossref] [PubMed]
7. Bong CL, Brasher C, Chikumba E, et al. The COVID-19 Pandemic: Effects on Low- and Middle-Income Countries. Anesth Analg 2020;131:86-92. [Crossref] [PubMed]
8. Osseni IA. COVID-19 pandemic in sub-Saharan Africa: preparedness, response, and hidden potentials. Trop Med Health 2020;48:48. [Crossref] [PubMed]
9. McMahon DE, Peters GA, Ivers LC, et al. Global resource shortages during COVID-19: Bad news for low-income countries. PLoS Negl Trop Dis 2020;14:e0008412. [Crossref] [PubMed]
10. Lodigiani C, Iapichino G, Carenzo L, et al. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res 2020;191:9-14. [Crossref] [PubMed]
11. Dinmohamed AG, Visser O, Verhoeven RHA, et al. Fewer cancer diagnoses during the COVID-19 epidemic in the Netherlands. Lancet Oncol 2020;21:750-1. [Crossref] [PubMed]
12. Ranganathan P, Sengar M, Chinnaswamy G, et al. Impact of COVID-19 on cancer care in India: a cohort study. Lancet Oncol 2021;22:970-6. [Crossref] [PubMed]
13. Webster P. Virtual health care in the era of COVID-19. Lancet 2020;395:1180-1. [Crossref] [PubMed]
14. Pramesh CS, Badwe RA. Cancer Management in India during Covid-19. N Engl J Med 2020;382:e61. [Crossref] [PubMed]
15. Singhania N, Bansal S, Nimmatoori DP, et al. Current Overview on Hypercoagulability in COVID-19. Am J Cardiovasc Drugs 2020;20:393-403. [Crossref] [PubMed]
16. Monaghesh E, Hajizadeh A. The role of telehealth during COVID-19 outbreak: a systematic review based on current evidence. BMC Public Health 2020;20:1193. [Crossref] [PubMed]
17. Mehta A, Vasudevan S, Parkash A, et al. COVID-19 mortality in cancer patients: a report from a tertiary cancer centre in India. PeerJ 2021;9:e10599. [Crossref] [PubMed]
18. Lee LY, Cazier JB, Angelis V, et al. COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study. Lancet 2020;395:1919-26. [Crossref] [PubMed]
19. Liang W, Guan W, Chen R, et al. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Lancet Oncol 2020;21:335-7. [Crossref] [PubMed]
20. Mehta V, Goel S, Kabarriti R, et al. Case Fatality Rate of Cancer Patients with COVID-19 in a New York Hospital System. Cancer Discov 2020;10:935-41. [Crossref] [PubMed]
21. van de Haar J, Hoes LR, Coles CE, et al. Caring for patients with cancer in the COVID-19 era. Nat Med 2020;26:665-71. [Crossref] [PubMed]
22. Monroy-Iglesias MJ, Tagliabue M, Dickinson H, et al. Continuity of Cancer Care: The Surgical Experience of Two Large Cancer Hubs in London and Milan. Cancers (Basel) 2021;13:1597. [Crossref] [PubMed]
23. Kunisaki KM, Janoff EN. Influenza in immunosuppressed populations: a review of infection frequency, morbidity, mortality, and vaccine responses. Lancet Infect Dis 2009;9:493-504. [Crossref] [PubMed]
24. Bitterman R, Eliakim-Raz N, Vinograd I, et al. Influenza vaccines in immunosuppressed adults with cancer. Cochrane Database Syst Rev 2018;2:CD008983. [Crossref] [PubMed]
25. Wang H, Zhang L. Risk of COVID-19 for patients with cancer. Lancet Oncol 2020;21:e181. [Crossref] [PubMed]
26. Zhang L, Zhu F, Xie L, et al. Clinical characteristics of COVID-19-infected cancer patients: a retrospective case study in three hospitals within Wuhan, China. Ann Oncol 2020;31:894-901. [Crossref] [PubMed]
27. Abou-Ismail MY, Diamond A, Kapoor S, et al. The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management. Thromb Res 2020;194:101-15. [Crossref] [PubMed]
28. Guan WJ, Liang WH, Zhao Y, et al. Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis. Eur Respir J 2020;55:2000547. [Crossref] [PubMed]
29. Sharpless NE. COVID-19 and cancer. Science 2020;368:1290. [Crossref] [PubMed]