DISCUSSION

Since the outbreak of COVID-19 in China, the medical care system has been profoundly affected by cancer patients, including those with NPC. Compared with that within 20 weekdays before the launch of the epidemic control policies, the number of outpatient visits after January 31, 2020, decreased significantly. Most of the patients from other provinces were prone to be affected by traffic restrictions. Patients from epidemic areas had to take a medical observation for 14 days after arriving in new cities. As a result, a considerable part of patients failed to arrive at hospital on time, leading to a significantly decreased the number of outpatient visits, which was subsequently followed by shrunken number of inpatients, extended average length of stay as well as reduced bed turnover rate. The number of patients undergoing radiotherapy also decreased as an effect of less patient visits.

In comparison, the waiting time for pathological consultation and imaging examinations was shorter than before due to decreased patient visits and appointments. Considering that the COVID-19 can spread through droplets or direct contact,7 the number of endoscopic operations was strictly limited. There were 6 patients in the outpatient clinics considered to have nasopharyngeal mass, but the biopsy could not be done by endoscopy in time. As a requirement of patient distancing, the capacity of radiotherapy and related work was reduced, so the immobilization and simulation, validation of position and plan, and initiation of radiotherapy were all delayed. Besides, extra effort for COVID-19 screening with a standard workup of epidemiological history inquiry, temperature monitoring and chest CT added to the waiting time, also leading to the postponing of diagnosis and radiotherapy of NPC.

It has been reported that the delay for anti-tumor treatment in patients with tumor may affect efficacy. It was found that delay in diagnosis correlates with the stage of nasopharyngeal carcinoma.8 Sharon et al reported that long diagnose-to-treatment interval to radiotherapy contributes to poor clinical outcome for nasopharyngeal carcinoma patients.3 Liang et al also demonstrated that increasing waiting time for radiotherapy beyond 30 days was detrimental to survival.4 Chen et al confirmed that prolonged wait time (>4 weeks) was an independent unfavorable prognostic factor for patients with nasopharyngeal carcinoma.5 Another study confirmed similar results.6 Based on these evidence, we sought to reduce the waiting time by adding another cycle of induction chemotherapy to the scheduled treatment for those who could not get access to radiotherapy in time. For patients who did not receive increased chemotherapy courses, the median waiting time prior to radiotherapy was significantly longer after COVID-19 outbreak. Telephone contact revealed that the reasons for the lack of compensatory chemotherapy included that local hospitals refused to accept patients who had been treated in other hospitals, patients refused to increase or could not tolerate additional chemotherapy courses. The median waiting time for initiation of radiotherapy is significantly longer since the outbreak.


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For patients who had started radiotherapy, considering the aggregation of people in the infusion center and impaired immunity of patients undergoing radiotherapy and chemotherapy, the hospital suggests minimizing intravenous infusion with serious adverse reactions. Patients who received concurrent chemotherapy might experience severe hematologic toxicities and gastrointestinal reactions.9,10 So the completion rate of concurrent chemotherapy was lower than before. Liu et al reported that 200 mg/m2 of concurrent cisplatin could be the optimal dose for the NPC patients who achieved response after induction chemotherapy.11 Patients receiving higher cumulative dose of cisplatin showed significantly improved 3-year progression-free survival (PFS) and distant metastasis-free survival (DMFS) compared with lower dose patients. Ou et al demonstrated that total dose of cisplatin more than 300 mg/m2 was independent prognostic factors for DMFS, disease-free survival (DFS) and overall survival (OS) in NPC patients.12 However, several articles retrospectively reported that IMRT alone achieves similar survival outcomes compared with concurrent chemoradiotherapy in locally advanced NPC patients.13,14 In our cohort, whether the reduction of concurrent platinum would detriment patients’ outcome will need to be closely followed up in future.

Liang et al,15 recently reported that 1% of 1590 COVID-19 cases had a history of cancer, the proportion of COVID-19 infected cancer patients was higher than that of overall cancer incidence rate in Chinese population (0.29%). Cancer patients had a higher risk of developing severe illness than non-cancer patients (39% vs 8%). Patients who had received chemotherapy in the past month were more likely to get worse (75% vs 43%). Therefore, Liang et al suggested that in the epidemic areas, delaying chemotherapy or elective surgery could be considered for stable cancer. However, for the tumor with locally advanced stage, poor dedifferentiation and rapid progression, for example, nasopharyngeal carcinoma, we suggested that the patients should be treated in time, in case the optimal timeframe of treatment is missing. For the patients undergoing chemotherapy, replacement with less toxic chemotherapy agents, reduction of treatment intensity, delaying or omitting concurrent chemotherapy could also be considered, so as to minimize the risk of COVID-19 infection. How to make the best choice between timely anti-cancer treatment and avoiding COVID-19 related risk is still worth thinking and further investigation. According to the urgency of anti-tumor treatment, it may be a feasible way to develop differentiated strategies.

The proportion of non-local patients is similar in two groups. As mentioned above, the reasons for the delay of diagnosis and treatment include traffic restrictions. We consider that the countermeasures for traffic restrictions under the epidemic include: (i) to refine the patient management, including using big data of travel to analyze and assess the risk of patients infected with COVID-19, so as to improve the efficiency of diagnosis and treatment; (ii) to reduce the treatment interruption and delay caused by traffic blockade through telemedicine and other technologies; (iii) to strengthen academic cooperation and alliances among hospitals in different regions, so as to reduce the difference of medical level among regions.

There were several limitations of this study. Firstly, selection bias is unavoidable for its retrospective nature, with small samples in a single center. Secondly, this study focuses on the delay in the diagnosis and treatment path. At present, there are no long-term survival follow-up data to fully evaluate the impact of the delay on the prognosis of patients.

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