The outcomes of cancer patients vary among institutions and countries due to differences in varieties of cancers; prevention and screening policies; stage at diagnosis and access to adequate specialized healthcare(18, 19). Better disease outcomes in HNSCC patients are basically related to early diagnosis, prompt treatment (ideally with a multidisciplinary approach), early rehabilitation and avoiding subsequent exposure to known risk factors such as tobacco and alcohol.(20) During COVID-19 pandemic, all these domains were affected since healthcare systems turned human and material resources into the treatment of infected patients. The North American Center for Disease Control(8) recommendations to suspend all elective healthcare and to provide only urgent and emergency treatment, were followed by numerous national and international medical organizations. In many countries, hospitals have converted operating suites into intensive care rooms due to the large proportion of patients with respiratory failure. As one of the indirect consequences, we will face an increase in the mortality ratio for chronic and non-communicable diseases. A likely increase in the risk of death or disability from stroke is expected.(21) Surprisingly, hospitalizations for acute myocardial infarction declined in northern Italy and in California, during the Covid-19 pandemic, more than would be expected on the basis of typical seasonal variation alone.(22, 23).
Little organized guidance was afforded surrounding urgent systemic treatment, radiation therapy, and elective surgery for cancer patients.(5, 24, 25) There is evidence highlighting the effects of COVID-19 pandemic on cancer care. Two Chinese reports showed that the COVID-19 pandemic was associated with increased severe events and cancer related deaths that were attributed to impediments to oncologic care(26, 27). Lai et al.(28) analyzed the recent changes in cancer care delivery in response to COVID-19. Population-based health records in England, and also USA Surveillance, Epidemiology, and End Results (SEER) data were used to estimate an excess of 6,270 cancer deaths at 1 year in England and 33,890 in the USA. It is ,therefore, necessary to reduce delays in cancer diagnosis, resume disrupted treatment, as well as to reallocate the resources diverted during the COVID-19 pandemic.(29)
The understanding of the natural history of untreated cancer is essential to appreciate the effects of the COVID-19 pandemic on the survival expectations of cancer patients. The evolution of a HNSCC is rapid, from initial presentation until it becomes untreatable.(30) About 50% of untreated individuals will die in four months, only 12% will survive more than 12 months and almost none will survive for five years.(4, 31, 32)
Treatment package time has significant prognostic impact in HNSCC patient outcomes; and timeliness of care delivery is regarded as a major quality metrics of oncologic care.(1, 3, 33-36)
This study employs HNSCC as a model to estimate the impact of COVID-19 pandemic on its worldwide cancer mortality considering the reduction of medical care volume during the outbreak. The mortality of those patients with HNSCC is closely related to presenting stage and also to longer time to treatment initiation, both affected when attention is diverted from cancer care. Thus, HNSCC is an appropriate disease to analyze the COVID-19 pandemic in terms of excess deaths, to propose how to reduce them and also to ascertain how much time will be needed to return to normal after the expected surge in patients presenting after the pandemic.
Although the model was designed to estimate the impact on increased risk of dying due to the outbreak for head and cancer patients, if considering that HNSCC represent only around 4% of all cancer worldwide, one can extrapolate that the toll of additional cancer deaths due to the COVID-19 outbreak to be in the millions, a number way higher than the deaths due to COVID-19 (close to 400,000 in early June, 2020), unfortunately. Nevertheless, to afford more accurate estimates the model should be adjusted to each individual clinical setting; covariates; and different TTI risk values for each cancer. Even with otherwise imprecise estimates it is evident that the number of deaths due cancer and other diseases will be substantially higher than those directly caused by COVID-19, in the aftermath, despite efforts at mitigation.
Considering the existing heterogeneity among different healthcare services around the globe in terms of the capacity for admitting newly diagnosed HNSCC patients, different treatment recommendations, diverse limitations in access to material resources and technologies, and reimbursement policies and procedures, one could expect a great variability in terms of capacity to accommodate any expansion of healthcare delivery after the pandemic period. Already frail healthcare networks will worsen due to economic recession and consequent reduction in healthcare expenditures in low-income and middle-income countries.(19, 37) Historically, recessions contribute to increases in mortality among the more vulnerable populations, and in cancer patients especially due to COVID-19 it should not be different.(38-40)
We have developed a mathematical model based on the estimated hazard identified by Murphy et al. to predict impact of the COVID-19 outbreak on additional risk of dying from HNSCC and also to propose some mitigation scenarios. The assumptions used in this study, were based on 51,655 patients from the National Cancer Data Base and indicated that 67 days was the nonzero threshold, maintained in the validation set. The mortality risk rises substantially after 67 days, after adjusting for covariates. Time to diagnosis and adequate staging, pre-treatment mortality ratio and the number of patients treated with palliative care were not considered, and consequently, overall HNSCC mortality risk may be even higher as time to treatment initiation increases. The mathematical model proposed here can be useful and may be adapted for other malignancies in which a time-to-treatment-initiation-dependent mortality risk exists.
As shown, a smaller decline in healthcare delivery during the outbreak and a more rapid and pronounced expansion afterwards will engender a quicker return to baseline mortality rates and reduce the additional risk of dying due to longer TTI. Our model cannot address different capacities of diverse healthcare systems or the access to treatment modalities in varied geographic areas. The financial and human resources required to increase access to radiation therapy, surgical treatment, and systemic treatment are likely to prove limiting in many regions. Our study provides data that can be used for individual institutions or entire national health systems to evaluate strategies and to prepare guidelines, infrastructure and their workforce to face the upcoming challenges. As demonstrated with the simulated data using the COCIC calculator, the scenario of no mitigation is the one that brings the most damage to the head and neck cancer population, it creates a novel baseline TTI that in most of the cases are followed by a long-lasting increase in additional deaths. The modelling of the data also showed that even a small increment of 5% volume in oncology services provided can bring the additional risk to an end; moreover, it appears in most of the simulations that an effort between 10 to 20% increase in medical care during the mitigation period results in return to baseline in 6 to 12 months in most of the scenarios tested.
We developed an easy-to-use, accurate instrument (COCIC), capable of predicting the impact of delayed treatment of head and neck cancer patients due to the COVID-19 pandemic. The tool is free and available online and also allows estimating mitigation strategies to reduce the associated mortality in the post-outbreak era in different scenarios and different diseases.
In conclusion, the proposed model demonstrates that the more the healthcare delivery is maintained during the COVID-19 outbreak and also the more it is increased during the mitigation period, the sooner will be the recovery and smaller the additional risk of death due prolonged time to begin treatment in an already stressed system(41). This impact of COVID-19 pandemic on cancer patients is inevitable, but it is possible to minimize it with a planned effort.