The impact of the COVID-19 pandemic on head and neck cancer patients.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) poses an unprecedented challenge to the global healthcare system [1], including the delivery of standard care to patients with cancer. In order to control the rapid and aggressive spread of COVID-19 since December 2019, the City of Wuhan that was the epicenter of the epidemic in China, implemented strict city lockdown and community quarantine for more than 2 months (from Jan 23 to April 8, 2020) that significantly halted the growth of infected patients. During this time, almost all in-hospital treatment for cancer patients was interrupted, with radiation therapy delivered only for selected patients with curative purposes following strict protection procedures.

Head and neck cancer (HNC) patients represented a major clinical challenge in treatment decision-making facing this highly contagious and potentially fatal infectious disease. On one hand, surgery, radiation therapy (RT) and chemotherapy (CT) were mainstays in the treatment of early and locally advanced HNC with favored prognosis. Immunotherapy plus chemotherapy also brought substantial survival benefit to recurrent/metastatic (R/M) HNC patients [2], [3], [4], [5], [6]. On the other hand, cancer patients were more susceptible to SARS-Cov-2 infection and were more likely to develop severe and critical COVID-19 when infected [7], [8], [9]. Frequent visit to hospital in the epidemic region and receiving anti-cancer treatments with immunosuppressive properties (e.g. chemotherapy) might greatly increase the risk of getting infected. Balancing the benefit from in-hospital anti-cancer treatment and the risk of getting SARS-Cov-2 was crucial in the care of HNC cancers. Considering that radiation therapy play a critical role in HNC, the suspension of radiation therapy might lead to disease progression in these patients. It was suggested that life-saving chemotherapy and radiotherapy with curative intent should be reserved and prioritized under strict quarantine measures in lung cancer patients [10]. However, data were lack regarding HNC patients.

In order to understand the impact of treatment suspension due to COVID-19 epidemic on HNC patients, we studied the clinical outcome of HNC patients who were undergoing anti-cancer treatments prior to the outbreak of COVID-19 and subsequently discontinued their in-hospital treatments in our cancer center. A total of 117 patients were eligible for analysis (Clinical characteristics in Supplementary Table S1). 49 patients were with early/locally advanced diseases undergoing definitive treatment including postoperative adjuvant RT or induction CT followed by concomitant chemoradiotherapy (CRT), 68 were with recurrent/metastatic diseases undergoing systemic therapy including CT, target therapy, immunotherapy or in combination.

71 patients had treatment discontinuation, among whom 22 (31.0%) had cancer progression or death (Table 1 ). 23 patients discontinued definitive therapy including 13 patients undergoing postoperative adjuvant RT and 10 undergoing induction CT followed by CRT, among whom 3 (13.0%) patients suffered from disease progression (Table 1). For R/M patients receiving systemic therapy including chemotherapy or chemotherapy plus immunotherapy/target therapy, those switching to out-hospital oral chemotherapy (mainly oral S1 or capecitabine) had less disease progression compared with those having total treatment suspension (2/12 [16.7%] vs. 19/48 [39.6%], P < 0.001) (Table 1). No SARS-Cov-2 infection was confirmed in these patients. These results indicated that treatment continuity for in-hospital patients under proper protection and for out-hospital patients were reasonable for HNC patients.

Table 1

Outcomes of patients with head and neck cancers without SARS-CoV-2 infection treated in the Zhongnan Hospital of Wuhan University.

	Definitive therapy (n = 49)			Systemic therapy for R/M patients (n = 68)			Total (n = 117) n (%)
	Adjuvant RT (n = 18) n (%)	Definitive CRT (n = 14) n (%)	Induction CT (n = 17) n (%)	CT (n = 39) n (%)	Oral CT and targeted therapy (n = 5) n (%)	CT and Immunotherapy (n = 24) n (%)
Treatment on schedule	2 (11.1)	6 (42.9)	6 (35.3)	2 (5.1)	3 (60.0)	3 (12.5)	22 (18.8)
Switching to oral chemotherapy	3 (16.7)	1 (7.1)	8 (47.1)	10 (25.6)	0 (0.0)	2 (8.3)	24 (20.5)
Treatment interruption	13 (72.2)	7 (50.0)	3 (17.6)	27 (69.2)	2 (40.0)	19 (79.2)	71 (60.7)
Reports of progression or death*	0/3 (0.0)	0/1 (0.0)	0/8 (0.0)	2/10 (20.0)	NA	0/2 (0.0)	2/24 (8.3)
Reports of progression or death△	2/13 (15.4)	1/7 (14.3)	0/3 (0.0)	15/27 (55.6)	0/2 (0.0)	4/19 (21.1)	22/71 (31.0)

SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; RT, radiotherapy; CT, chemotherapy; CRT, concomitant radiochemotherapy; R/M, recurrent/metastatic. NA, not applicable.

Reports of progression or death due to treatment switching to oral chemotherapy; △Reports of progression or death due to treatment interruption.

Interestingly, for those R/M HNC patients who discontinued anti-cancer treatment, a subgroup of patients who had chemotherapy in combination with immunotherapy had significantly less disease progression as compared with patients without immunotherapy (4/19 [21.1%] vs 15/27 [55.6%], P = 0.003) (Table 1). This might be a result of durable immune activation and prolonged disease response to immunotherapy seen in clinical studies [2], [3], [4], [5], [6]. However, although temporary interruption of immunotherapy might be safe for certain R/M HNC patients, the long-term outcome of these patients remains unknown.

Next, we investigated the risk factors associated with disease progression during treatment discontinuation. We found that non-nasopharyngeal carcinoma (non-NPC) patients (adjusted OR = 5.233 [1.278–21.433], P = 0.021), R/M HNC patients undergoing chemotherapy alone (adjusted OR = 9.259 [2.175–39.407], P = 0.003) were more prone to have disease progression (Table 2 ). However, this effect was not observed in R/M HNC patients received CT plus immunotherapy, confirming that CT plus immunotherapy was a favorable choice for R/M HNC patients. Compared with patients switching to oral CT, treatment interruption was associated with more progression disease (adjusted OR = 5.880 [1.070–32.302], P = 0.042) (Table 2), indicating that oral CT may be a choice to reduce the disease progression rate in this cohort of patients during the outbreak of COVID-19.

Table 2

Univariable and multivariable tests of association of clinical and treatment parameters with disease progression in 117 HNC patients without COVID-19 in the Zhongnan Hospital of Wuhan University.

Variables	Univariable analysis		Multivariable analysis
	OR (95% CI)	P	OR (95% CI)	P
Gender (Male ref)	0.688 (0.183–2.584)	0.579
Age (continuous)	1.019 (0.982–1.058)	0.312
Cancer types (Non-NPC vs NPC ref)	6.562 (1.831–23.515)	0.004	5.233 (1.278–21.433)	0.021
Treatment undergoing
Definitive treatment (ref)
CT for R/M patients	11.848 (3.319–44.727)	<0.001	9.259 (2.175–39.407)	0.003
oral CT + Target therapy for R/M patients	NA	NA
CT + Immunotherapy for R/M patients	3.067 (0.628–14.983)	0.166
Treatment disturbance
Switching to oral CT (ref)
Treatment on schedule	NA	NA
Treatment interruption	4.939 (1.067–22.864)	0.041	5.880 (1.070–32.302)	0.042

HNC, head & neck cancer; COVID-19, coronavirus disease-19; 95% CI, 95% confidence interval; NPC, nasopharyngeal carcinoma; CT, chemotherapy; R/M, recurrent/metastatic; OR, odds ratio; NA, not applicable.

Collectively, as cancer care and COVID-19 collide, there is no easy and universal solution to oncologic care. Although the pandemic scenario is new, the risk of mortality due to COVID-19 is seemingly lower than the risk of cancer-related death [11]. Prevention and protection measurements against SARS-Cov-2 are also greatly improved. Our work suggested that in-hospital treatment continuation with curative purposes under proper protection and a switch to oral chemotherapy for R/M HNC patients were suitable in the quarantine period.

Role of the funding source

The sponsor had no role in the design, analysis or writing of this article.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.