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Determining the impact of COVID-19 pandemic on adjuvant therapy for oral cancer – A matched-pair analysis

1 Department of Head and Neck Oncology, Tata Memorial Centre and HBNI, Mumbai, Maharashtra, India
2 Department of Radiation Oncology, Tata Memorial Centre and HBNI, Mumbai, Maharashtra, India
3 Department of Medical Oncology, Tata Memorial Centre and HBNI, Mumbai, Maharashtra, India

Date of Submission18-Feb-2021
Date of Decision09-May-2021
Date of Acceptance29-Jun-2021
Date of Web Publication28-Oct-2022

Correspondence Address:
Pankaj Chaturvedi,
Department of Head and Neck Oncology, Tata Memorial Centre and HBNI, Mumbai, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijc.IJC_186_21


Background: The ongoing coronavirus disease 2019 (COVID-19) pandemic has hard-pressed the health care systems beyond their capabilities, causing a lack of appropriate cancer treatment delivery. The aim of this study was to assess the impact of pandemic-related restrictions on adjuvant therapy delivery for oral cancer patients during these demanding times.
Materials and Methods: Oral cancer patients who were operated on between February and July 2020 and scheduled to receive prescribed adjuvant therapy during the COVID-19-related restrictions (Group I) were included in the study. The data were matched for the length of hospital stay and type of prescribed adjuvant therapy, with a set of patients who were similarly managed 6 months preceding the restrictions (Group II). Demographic and treatment-specific details, including inconveniences faced in procuring prescribed treatment, were obtained. Factors associated with delay in receiving adjuvant therapy were compared using regression models.
Results: A total of 116 oral cancer patients were considered for analysis, comprising 69% (n = 80) adjuvant radiotherapy alone and 31% (n = 36) concurrent chemoradiotherapy. The mean hospital stay was 13 days. In Group I, 29.3% (n = 17) of patients were not able to receive any form of their prescribed adjuvant therapy at all, which was 2.43 times higher than Group II (P = 0.038). None of the disease-related factors significantly predicted delay in receiving adjuvant therapy. Of the delay, 76.47% (n = 13) was present during the initial part of the restrictions, with the most common reason being unavailability of appointments (47.1%, n = 8), followed by inability to reach treatment centers (23.5%, n = 4) and redeem reimbursements (23.5%, n = 4). The number of patients who were delayed the start of radiotherapy beyond 8 weeks after surgery was double in Group I (n = 29) than in Group II (n = 15; P = 0.012).
Conclusions: This study highlights a small part of the rippling effect the COVID-19 restrictions have on oral cancer management and pragmatic actions may be needed by policymakers to deal with such challenges.

Keywords: Adjuvant therapy, cancer, chemotherapy, COVID-19, radiotherapy
Key Message: The Covid-19 pandemic-related restrictions have had a detrimental impact on the outcomes of oral cavity cancers. Unavailability of appointments and difficulty reaching treatment centers were the most common reasons for not completing adjuvant therapy.

How to cite this URL:
Singh AG, Sharin F, Ramalingam N, Tuljapurkar V, Mummudi N, Prabhash K, Chaturvedi P. Determining the impact of COVID-19 pandemic on adjuvant therapy for oral cancer – A matched-pair analysis. Indian J Cancer [Epub ahead of print] [cited 2022 Dec 2]. Available from:

  Introduction Top

In the past few months, the novel coronavirus has infected people across continents and cultures. To curb the spread of this virus, governments have imposed restrictions on travel and implemented social distancing measures that have stalled health care facilities. Among the various health conditions and comorbidities that increase the risk of contracting the virus, cancer patients are particularly vulnerable due to the disease itself and the corresponding treatments that often cause immunosuppression. In India, oral cancer is the most common cancer among men, and it imposes a significant burden, both in terms of direct and indirect loss to the economy.[1] Because of the obvious location of cancer and the fear of the risk of transmission of the coronavirus, most oral cancer detections might have been neglected during the coronavirus disease 2019 (COVID-19) pandemic and could lead to more advanced stages of presentation.[2]

For the patients who do manage to receive treatment, the timeliness of receiving and completing cancer treatment is of paramount importance as a delay at one time point cascades subsequently, drastically impacting survival outcomes. For oral cancer, surgery is the primary treatment for most cases followed by risk-based adjuvant therapy in the form of radiotherapy with or without concurrent chemotherapy. Once the surgery is performed, an appropriate adjuvant therapy must be instituted at the earliest to maximize survival outcomes.[3],[4] Microscopic residual tumor progression has been shown to occur during prolonged planning periods, delayed surgical recovery, and breaks due to treatment toxicity.[5],[6] Surgeons and physicians have the capacity to manage most of the above-mentioned factors that cause delays to deliver appropriate adjuvant therapy at the earliest. With the pandemic resulting in sudden restrictions and halts in the routine lives of almost every individual across the globe, its true effect on cancer patients is unfathomable.

To adjust to the new normal, a number of recommendations have been suggested, which include virtual consultations, follow-ups, and rerouting patients to their regional cancer care facilities in an effort to minimize exposure.[6],[7] Unfortunately, the ongoing pandemic has stretched the health care systems beyond their capabilities, precipitating into the lack of appropriate treatment delivery for cancer patients. In a country like India where the cancer care delivery system is already fragile, the repercussions of quarantine and restrictions are still to be fully understood. The aim of the study was to evaluate the impact of pandemic-related logistic restrictions on oral cancer patients who were scheduled to receive their adjuvant therapy during these trying times.

  Materials and Methods Top

The current study considers a subset of a larger research protocol approved by the Institutional Review Board of Tata Memorial Hospital. Restrictions in India were enforced from March 22, 2020, after which stringent protocols for cancer management were instituted to contain the spread of the novel coronavirus. We reviewed the details of consecutive oral cancer patients who underwent surgery at our Head and Neck Oncology Unit between February and July 2020 and who were scheduled to receive their prescribed adjuvant therapy during the coronavirus disease 2019 (COVID-19)-related imposed restrictions (Group I). Adjuvant therapy was prescribed as per the institutional protocol for Stage III/IV disease and/or other adverse pathologic factors. These patients were propensity matched (caliper value at 0.05, i.e., 95% matching) for the duration of hospital stay after surgery and the type of prescribed adjuvant therapy (radiotherapy alone or concurrent chemoradiotherapy) with a set of patients who were similarly managed 6 months prior to the restrictions (Group II). In accordance with most studies, we considered a delay in treatment if the patient was not able to receive or complete the prescribed therapy within a 100 overall treatment time (OTT).[8],[9],[10] Delays or not receiving prescribed concomitant chemotherapy dose was also considered a delay. We considered only those patients who either had to complete or begin their prescribed adjuvant therapy after the strict restrictions were instituted after March 2020. During this time, we maintained telephonic contact with all patients who were undergoing active treatment or were on follow-up. The demographic details were obtained from the electronic medical records of the hospital that were being maintained prospectively. All cancers were staged as per the AJCC (American Joint Committee on Cancer), eighth edition, classification. We aimed to gather the treatment-specific details, including the inconveniences faced in obtaining prescribed treatment during the period of the restrictions. We analyzed the data using SPSS Version 21.0 (IBM, Armonk, NY). Regression models were used to identify the factors associated with delay in receiving adjuvant therapy. Kaplan–Meier method and log-rank tests were used to calculate the overall survival (OS) and disease-free survival (DFS).

  Results Top

From February to July 2020, 58 oral cancer patients were operated in our Head and Neck Oncology Unit (Group I). Group II consisted of 58 patients matched for the duration of hospital stay (mean = 13.55 days) and the type of prescribed adjuvant therapy. The clinical and pathological demography is given in [Table 1]. Patients visited the center from across 10 states of India with maximum numbers from Maharashtra (n = 40), followed by Uttar Pradesh (n = 27) and Bihar (n = 18) [Figure 1]. The median age of Group I was 44 ± 11.39 years and Group II was 49 ± 13.96 years. With respect to subsites, 57.9% (n = 22) of group I were buccal mucosa cancers and a majority of group II (n = 20, 55.6%) were oral tongue cancers. A majority of cases were advanced cancer (Stage III–IV) with no statistical difference between the groups (P = 0.762). The treatment demography is given in [Table 2]. The median hospital stay was 12 ± 6.9 days for Group I and 10 ± 10.2 days for Group II. A median of 30 ± 14.2 days was present for Group I and 28 ± 16.8 days for Group II from the date of discharge till the start of adjuvant therapy. Among both groups, 12.9% of cases had major complications (Clavien–Dindo III–IV) in the postoperative period that could have affected delay in receiving adjuvant treatment.
Figure 1: Treatment time distribution among patients who were prescribed adjuvant therapy scheduled to be received during the restrictions (Light shaded area – greater than 6 weeks, dark shaded area – greater than 8 weeks)

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Table 1: Clinical and pathological demography of the patients

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Table 2: Demography of the treatment details

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Based on the postoperative pathology reports, 69% (n = 40) were prescribed radiotherapy alone and 31% (n = 18) were prescribed concurrent chemotherapy in both groups. Out of these, 29.3% (n = 17) were not able to receive any form of adjuvant therapy in Group I, whereas this number was 2.43 times lower in Group II (12.1%, n = 7, P = 0.038). None of the disease or treatment-related factors significantly predicted a delay in completing adjuvant therapy [Table 1]. Another 8.4% (n = 5) in both groups began their treatment but were not able to complete it, with a median treatment break of 3.5 ± 8 days. Of the delays, 76.47% (n = 13) were for the cases that required to start their adjuvant therapy during the initial part of the restrictions, that is March and April 2020. Also, 11.7% (n = 2) of the patients who could not complete their adjuvant therapy in Group I had locoregional disease failure within 3 to 5 months of surgery that could not be salvaged. The median follow-up of both groups was 9 months. There was no difference in DFS (odds ratio [OR] = 1.618, 95% confidence interval [CI] =0.580–4.517, P = 0.358) and OS (OR = 0.940, 95% CI = 0.059–15.049, P = 0.965) between the two groups. Based on the data from the telephonic follow-ups and electronic medical records, the most common reason was due to the restrictions in place (70.6%, n = 12). Three patients discontinued treatment due to personal reasons, and 11.8% (n = 2) were not fit to receive any prescribed further treatment. Among the 17 patients who were delayed by the restrictions imposed, 47.1% (n = 8) were due to a lack of availability of appointments, 23.5% (n = 4) were due to the inability to reach treatment centers, 23.5% (n = 4) could not redeem government schemes for reimbursements, and 5.9% (n = 1) were refused administration of chemotherapy [Figure 2]. Assuming that all patients were able to access the prescribed adjuvant therapy and a minimum of 45 days was required to complete the adjuvant therapy, the number of patients who were delayed beyond 8 weeks after surgery were almost double in Group I (65.9%, n = 29) than in Group II (34.1%, n = 15; P = 0.012).
Figure 2: Distribution of patients who were delayed beyond 5 weeks during and before the COVID-19 pandemic. (C – COVID, PC – PRECOVID, Orange dot – Study institution)

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  Discussion Top

It is common knowledge to avoid any delay in treatment initiation from initial diagnosis in order to achieve the best survival outcomes.[11] The ongoing pandemic has resulted in a significant decrease in the number of new cancer diagnoses of common cancers compared with the previous years while the number of deaths have significantly increased.[12] This reflects a delay in diagnosis that will eventually lead to the presentation at more advanced stages and poorer clinical outcomes for these patients. At the same time, delay in completion of treatment is equally important. Although strong evidence exists demonstrating a significant negative impact on the local control and survival outcomes due to delay in OTT and time to adjuvant therapy among cancer patients, this is the first Indian study, to the best of our knowledge, discussing these delays for oral cancer in the context of the ongoing pandemic.[13],[14] Access to care issues related to rural geography, race/ethnicity, insurance, and other social factors also contribute to a delay in both diagnosis and completion of treatment. These delays often lead to tumor progression, psychological distress, need for patients to travel distances to higher centers, and reduced benefit of intervention. Our results reflect that most of the delays were in the early part of the pandemic when sudden restrictions were instituted. Matched to patients who were managed with a similar disease profile when these restrictions were not present, a significant decline in treatment completion was observed.

For the head and neck cancer patients who are eligible to receive adequate treatment, studies have reported reduced survival outcomes when delays are present in treatment completion.[3],[9] This treatment package time or OTT ranges from less than 11 weeks to within 100 days from surgery.[8],[9],[10] To circumvent delays caused due to treatment toxicities, many techniques have been attempted with varied success. Altered fractionation has been extensively studied to shorten the OTT at the cost of increased acute and short-term morbidity.[15] Studies have also shown that starting adjuvant radiation therapy more than 6 weeks after surgery is associated with a 50% relative decrease in OS.[10],[16],[17] The authors have reported incremental reduction in survival rates as the time between surgery and radiotherapy increased when the variables were analyzed categorically (adjusted hazard ratio [aHR] for 7 to ≤8 weeks = 1.09, 99% CI = 1.00–1.19; aHR for 8 to ≤10 weeks = 1.10, 99% CI = 1.01–1.19; aHR for >10 weeks = 1.12, 99% CI = 1.04–1.21). They found no benefit in terms of OS in starting radiotherapy in ≤4 weeks after surgery or 4 to ≤5 weeks after surgery relative to 5 to ≤6 weeks after surgery.[10] Considering a minimum of approximately 45 days with adjustable interruption is required to effectively complete the prescribed adjuvant therapy, treatment needs to be initiated within 8 weeks after surgery at the latest to complete treatment within the OTT. In our study, less than a third of the patients were able to receive their prescribed adjuvant therapy within 8 weeks after surgery during the restrictions imposed due to the pandemic. Applying this knowledge, very few patients diagnosed and treated during the pandemic would go on to stand a chance in completing their treatment. Although our study was not aimed to collect and report data on outcome measures, two of the patients returned with unsalvageable disease due to incomplete treatment, which has significantly shortened their survival.

During the ongoing pandemic, patients who were prescribed adjuvant therapy could not book appointments or were not able to reach their regional cancer centers for further management. Most centers refused to administer chemotherapy due to the heightened risk of contracting COVID-19 in an immunocompromised state. A few had indefinite delays in sanctioning their schemes for funding their treatment. Assuming that all patients were able to receive the prescribed adjuvant therapy at the time of analysis, less than half would still not be able to complete treatment and would exceed the OTT, as reflected in Group II as well. This staggering number reflects the lack of adequate cancer care pathways present in the country, including a lack of infrastructure and poor accessibility.

Gaps during radiotherapy, either scheduled or unscheduled, is another problem that causes delay most often due to toxicity, poor compliance, and socioeconomic factors. The delays experienced during the pandemic are examples of unscheduled gaps. Studies have shown that delays in the first 3 weeks of the adjuvant treatment that results in receiving less than 14 fractions are independently associated with a poorer OS (hazard ratio [HR] = 1.486, 95% CI = 1.122–1.966, P = 0.006) and the occurrence of distant metastasis (HR = 1.644, 95% CI = 1.047–2.583, P = 0.031).[18] In our study, among the ones that did manage to start their adjuvant therapy, the median delay was 3.5 days. We could not obtain details of the position of gap during the treatment. The most common reason for the delay was due to the sudden unavailability of appointments during this time the restrictions were announced. In fact, even among those who did manage to start their adjuvant treatment, 16.2% would not be completing it in the 100-day OTT.

The current results highlight a small part of the rippling effect this pandemic has on oral cancer patients. A large multicenter study from the National Cancer Grid also found the highest number of reductions in patient care in the months of April and May 2020, when the restrictions were the most stringent.[19] They found the largest reductions in terms of new patient registrations followed by outpatient services. Similar to their reasoning, we also believe that the delays were likely to reflect fear of infection and logistical issues due to the pandemic restrictions. Based on this, it is very important for policymakers to understand the various aspects of cancer care to mitigate the negative impact on the management of these patients. In the future waves of the pandemic, health care authorities need to communicate with patients and other professionals to understand the proper risk–benefit ratio of receiving these treatments during the pandemic. These hardships have also resulted in patients seeking care at centers that are in close proximity to their homes, a practice that needs to be reinforced in an effort to decentralize cancer care. Tele- and video consultations have become a reality that results in reduced hospital visits, less crowding within cancer centers, and triaging those in need of urgent care. As the situation is evolving, pragmatic actions may be needed to deal with the challenges these patients face, while ensuring their rights, safety, and well-being.

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Conflicts of interest

There are no conflicts of interest.

  References Top

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