Impact of COVID-19 on Disease Progression and Postoperative Complications in Patients with Head and Neck Cancer

Abstract

The COVID-19 pandemic has created a remarkable challenge for the healthcare system. The delayed presentation, diagnosis, and treatment of head and neck cancer during the COVID-19 pandemic is expected to adversely affect outcomes. COVIDSurg collaborative group in 2020 concluded surgery ≥ 4 weeks after a positive COVID-19 swab result was associated with a lower risk of postoperative mortality. The aim of this study is to assess the disease progression due to COVID-19 infection in patients with head and neck cancer planned for surgery and to analyze the postoperative complications in head and neck cancer patients who underwent surgery after COVID-19 infection. This is an ambispective observational study and included patients with head and neck cancer who recovered from COVID-19 infection and underwent surgery from June 2020 to May 2022. There were a total of 1849 patients with head and neck cancer operated in the mentioned study period during COVID-19 pandemic. One hundred fifty-nine patients had documented COVID-19 infection. One hundred two patients had oral cavity carcinoma (64%), and 38 patients had thyroid carcinoma (23.8%). Early disease was noted in 49 patients (30.8%) and locally advanced disease in 108 patients (67.9%). Mean duration of delay in surgery was 4 weeks. Disease progression was noted in 27 patients (17%) out of which 15 patients were inoperable. Thirty-seven out of 159 patients (23%) had postoperative complications, and it included 2 mortality. There was increased trend noted in pulmonary complications and hemorrhage when compared to pre-COVID-19 era. Due to COVID-19 pandemic, delayed elective head and neck cancer surgery has resulted in higher rates of inoperability. COVID-19 has been associated with increased postoperative pulmonary complications and hemorrhage.

Introduction

Globally, COVID-19 has reduced referrals, diagnoses, and treatments for cancer patients, raising concerns about an increase in cancer-related deaths in the near future [1, 2]. It is likely that the observed reductions in the number of newly diagnosed cancer cases during the pandemic were due to restrictions imposed at the national and local levels, change in guidelines for managing patients during different waves of the pandemic and perceptions that hospitals are high-risk areas for COVID-19 transmission [3].

Due to high viral loads of COVID-19 in the upper aero-digestive tract, all therapeutic and diagnostic procedures pose a high risk of viral transmission, but this risk is significantly higher in head and neck cancer (HNC) patients [4]. In the wake of the pandemic, head and neck cancer diagnoses have decreased and treatment initiation has been delayed [5].

Head and neck cancer encompasses a diverse set of cancers with varying prognosis, depending on the anatomical site, the stage, and the epidemiological factors involved. The doubling time of squamous cell carcinoma of the head and neck is short, so delays in diagnosis and treatment increase the risk of upstaging, inoperability, and more complex reconstructive procedures [5, 6]. Optimal survival and functional outcomes are achieved with timely multidisciplinary intervention for head and neck cancer (HNC) patients [7].

According to the COVIDSurg collaborative group in 2021, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection in order to reduce pulmonary complications and postoperative mortality [8]. Minor surgery should be delayed for at least 4 weeks and major surgery for 8–12 weeks following infection [9]. International guidelines for head and neck oncology management in COVID-19 patients concluded surgery should not be rescheduled for more than 4 to 6 weeks in high grade and high stage squamous cell cancers of the aerodigestive tract [10].

The aim of this study is to assess the disease progression due to COVID-19 infection in patients with head and neck cancer planned for surgery and to analyze the postoperative complications in head and neck cancer patients who underwent surgery after COVID-19 infection.

Materials and Methods

This is an ambispective observational study at a single tertiary cancer center in South India. It included patients with head and neck cancer who underwent elective surgery after recovering from laboratory confirmed SARS-CoV-2 infection from June 2020 to May 2022. Patients with head and neck cancer relapse, metastatic disease, and head and neck cutaneous neoplasm were excluded.

Data were collected from patient clinical records and hospital electronic medical records. The following information were collected from each patient: age, gender, comorbidities, performance status, COVID-19 infection-related information including symptoms and hospitalization, tumor site and stage at presentation as per AJCC staging (8th edition), time delay in surgery, addition of neoadjuvant treatment due to delay, disease progression during the delay, change in surgical plan in view of disease progression, preoperative cardiac and pulmonary risk evaluation, and 30-day postoperative morbidity and mortality data. Patients were recorded as having respiratory comorbidities if they had a diagnosis of asthma or chronic obstructive pulmonary disease (COPD).

Overall postoperative complication rate was compared with the data of pre-COVID-19 pandemic patient records from January 2019 to December 2019. The first lockdown was announced in March 2020 by the government of India. The surgical services were resumed in May 2020 with a strict COVID-19 cancer surgery protocol developed by institution COVID-19 team based on national and international guidelines. The Institutional Review Board and Ethics Committee approval was obtained.

The descriptive data were presented as mean or median values or as absolute numbers with percentages and proportions, as appropriate. A chi-squared test was used to test for differences between groups for categorical variables. Predictors of postoperative complications were analyzed using logistic regression models. Statistical analysis was performed using SPSS® statistical software (version 27).

Results

There were a total of 1849 patients with head and neck cancer operated in the mentioned study period during COVID-19 pandemic. Only 159 patients had documented COVID-19 infection and met the inclusion criteria. The mean age was 52 years and 66% of patients were males. Pre-existing respiratory comorbidity was noted in 8% of patients. Twenty-one percent of patients had history of smoking, 15% had history of tobacco chewing, and around 4% had history of drinking alcohol to excess. A total of 96 percent of patients were Eastern Cooperative Oncology group (ECOG) performance status 0 or 1 at time of presentation (Table 1).

Table 1.

Patient demographic data , comorbidities, and performance status

Characteristics	N (%)
Age
< 50 years    ≥ 50 years	70 (44) 89 (66)
Gender
Male   Female	105 (66) 54 (34)
Comorbidities
Diabetes mellitus   Hypertension   Bronchial asthma/COPD   Coronary artery disease	15 (10) 34 (21) 13 (8) 4 (3)
Habits
Smoking   Tobacco chewing   Alcohol	33 (21) 24 (15) 7 (4)
ECOG
0/1   2	153 (96) 6 (4)

COVID-19 Infection Profile

Seventeen patients were treated during the first lockdown in 2020, 93 patients were treated in 2021, and 49 patients were treated in 2022 in the above study period. Two third of patients were asymptomatic and were tested due to history of exposure or prior admission for surgery as a part of institute protocol. Out of 40 symptomatic patients, 17% were hospitalized with mild to moderate symptoms and for isolation.

Tumor Profile

Among the patients, oral cavity carcinomas predominated (64%), followed by thyroid carcinomas (24%). 33% of patients presented with T2 disease, 29% of patients had T4 disease, 19% of patients had T3, and 18% had T1 disease at presentation. As a result of COVID-19 infection, 82% of patients with locally advanced disease delayed their cancer evaluation. The majority (56 per cent) of patients had nodal involvement at first clinical visit. Overall 35% of patients presented with stage IV disease and 33% presented with stage III disease (Table 2).

Table 2.

Tumor profile at presentation

Tumor characteristic	N (%)
Subsite
Oral cavity   Thyroid   Salivary gland   Paranasal sinus   Larynx   Oropharynx   Cancer unknown primary	102 (64%) 38 (24%) 8 (5%) 6 (4%) 3 (2%) 1 (0.6%) 1 (0.6%)
T stage
Tx   Tis   T1   T2   T3   T4a   T4b	1 1 28 (18%) 53 (33%) 30 (19%) 42 (27%) 4 (2%)
N stage
0   1   2   3	69 (44%) 59 (37%) 24 (15%) 7 (4%)

Delay and Deviation

Mean duration of delay in surgery was 4 weeks. Five percent of patients had a delay of 8 weeks due to persistent COVID-related symptoms. Disease progression was noted in 27 patients (17%) out of which 15 patients were inoperable. There were 46 patients (29%) who received neoadjuvant chemotherapy as a result of a delay in surgery. This was documented as a deviation in the treatment plan by the multidisciplinary tumor board. Twenty-seven (17%) patients had a change in surgical plan as a result of disease progression that required additional flap procedures to close the defects.

Preoperative Assessment

All 159 patients underwent a chest x-ray and echocardiogram prior to surgery, as well as a cardiology and pulmonary fitness assessment. The CT thorax of 18 patients with symptomatic COVID-19 that required hospitalization and persistent respiratory symptoms showed mild to moderate changes in imaging. Ninety percent of patients were ASA grade 1, or 2 and 10% were ASA grade 3. A preoperative d-dimer test has been performed for 133 patients as part of an institute protocol since January 2021. There was an elevation of D-dimer in 65 patients (41%). These patients received perioperative thromboembolic prophylaxis.

Postoperative Complications

Thirty-seven out of 159 patients (23%) had postoperative complications, and it included 2mortality. The postoperative events in 37 patients were hemorrhage 24%, myocardial infarction 2.7%, pulmonary embolism 8.1%, pneumonia 8.1%, and inappropriate sinus tachycardia 56.7%. There was increased trend noted in pulmonary complications and hemorrhage when compared to pre-COVID-19 era.

Performance status was a significant predictor of postoperative complications. An elevated D dimer was associated with an increased risk of postoperative morbidity; however, the association was not statistically significant (p-0.06). It is interesting to note that in COVID-19 categories based on symptoms, comorbidities, tumor stage, and progression, the addition of neoadjuvant chemotherapy had no significant impact on postoperative complications. A greater level of postoperative intensive care support was required for patients who recovered from COVID-19 infection (Table 3).

Table 3.

Postoperative complications in study period and in pre-COVID-19 era. MI myocardial infarction, AF atrial fibrillation, IST inappropriate sinus tachycardia

Complications	Study population-documented COVID-19 infection, n = 159	Patients with no documented COVID-19 in the study period, n = 1690	Pre-COVID-19 era (Jan 2018–Dec2019) n = 2720
Mortality	2 (1.2%)↑	1 (0.06%)	1 (0.03%)
Morbidity	37 (23%)↑↑	104 (6.1%)	69 (2.5%)
Pulmonary embolism Pneumonia	3 (1.8%) 3 (1.8%)	3 (0.17%) 25 (1.4%)	0 1
Postoperative hemorrhage	9 (5.6%)	21 (1.2%)	39 (1.4%)
Cardiac event
MI   AF   IST	1 (0.6%) 0 27 (16.9%)	1 (0.05%) 3 (0.17%) NA	3 (0.1%) 2 (0.07%) NA

Discussion

There has been a significant impact on the management of cancer patients in many countries because of the COVID-19 pandemic[3]. Studies have shown that minor surgeries should be delayed for at least 4 weeks and major surgeries for 8 weeks following COVID-19 infection, provided that patient outcomes are not compromised; in addition, a comprehensive preoperative and ongoing assessment must be conducted to ensure optimal clinical decision‐making [8, 9].

A single month delay in treatment for early and locally advanced head and neck cancer increases mortality [11]. After weighing the pros and cons and adhering to international guidelines, a 4–6 weeks delay in surgery was noted in the study group. The reasons for delay in surgery were lockdown, travel restrictions, active COVID-19 infection, persistent symptoms, decreased postoperative morbidity, and logistic reasons. In spite of the minimum delay calculated according to international guidelines, there was a significant increase in disease progression and inoperability in the study population.

During the COVID-19 pandemic, there is a demonstrably increased incidence of postoperative morbidity.

There is strong evidence demonstrating an association between surgery on COVID‐19 patients and significant postoperative mortality, pulmonary, and thromboembolic complications [12]. There was a high rate of pulmonary complications in the study group, as well as an increase in postoperative hemorrhage The preoperative measurement of D-dimer is useful in assessing the risk of postoperative thromboembolic events in patients with head and neck cancer following a COVID-19 infection. The preoperative risk assessment and the surgeon-anesthetist team play a crucial role in timing the procedure after calculating the risk versus benefit.

The postoperative complication data were analyzed further, and no significant correlation was found between COVID-19 symptom category, pre-existing comorbidities, stage of the disease, and complexity of surgery. A large sample size observational study or a multicentric study will shed light on predictors of postoperative morbidity in patients undergoing surgery after a COVID-19 infection. Since the pandemic has ended, most centers are no longer performing routine preoperative COVID-19 tests for elective/emergency surgeries, but complications caused by long-term sequelae of COVID-19 still occur, and we should be vigilant in assessing the risk of postoperative morbidity in patients with previous COVID-19 infection.

Several limitations to the methodology exist, including the possibility of underreporting undiagnosed COVID-19 infection or infection causing only minor symptoms. This study did not identify a definitive marker that could predict postoperative complications. Predictors and risk stratification require a larger sample size.

Conclusion

Due to COVID-19 pandemic, delayed elective head and neck cancer surgery has resulted in higher rates of disease progression and inoperability. COVID-19 has been associated with increased postoperative pulmonary complications and hemorrhage in those with head and neck cancer. Cancer patient outcomes are still affected by COVID-19, despite the end of the pandemic.

Declarations

Ethics Approval

This study was conducted with the approval of the Institutional Review Board and Ethical committee of the Regional Cancer Center, Thiruvananthapuram.

Competing Interests

The authors declare no competing interests.