key: cord-0764582-wdoj3t6p authors: van Not, Olivier J.; van Breeschoten, Jesper; van den Eertwegh, Alfonsus J. M.; Hilarius, Doranne L.; De Meza, Melissa M.; Haanen, John B.; Blank, Christian U.; Aarts, Maureen J. B.; van den Berkmortel, Franchette W. P. J.; de Groot, Jan Willem B.; Hospers, Geke A. P.; Ismail, Rawa K.; Kapiteijn, Ellen; Piersma, Djura; van Rijn, Rozemarijn S.; Stevense‐den Boer, Marion A. M.; van der Veldt, Astrid A. M.; Vreugdenhil, Gerard; Boers‐Sonderen, Marye J.; Blokx, Willeke A. M.; Suijkerbuijk, Karijn P. M.; Wouters, Michel W. J. M. title: The unfavorable effects of COVID‐19 on Dutch advanced melanoma care date: 2021-10-22 journal: Int J Cancer DOI: 10.1002/ijc.33833 sha: 5aeee4dcc16e501beca1644f5e2e049c60cd4ac1 doc_id: 764582 cord_uid: wdoj3t6p The COVID‐19 pandemic had a severe impact on medical care. Our study aims to investigate the impact of COVID‐19 on advanced melanoma care in the Netherlands. We selected patients diagnosed with irresectable stage IIIc and IV melanoma during the first and second COVID‐19 wave and compared them with patients diagnosed within the same time frame in 2018 and 2019. Patients were divided into three geographical regions. We investigated baseline characteristics, time from diagnosis until start of systemic therapy and postponement of anti‐PD‐1 courses. During both waves, fewer patients were diagnosed compared to the control groups. During the first wave, time between diagnosis and start of treatment was significantly longer in the southern region compared to other regions (33 vs 9 and 15 days, P‐value <.05). Anti‐PD‐1 courses were postponed in 20.0% vs 3.0% of patients in the first wave compared to the control period. Significantly more patients had courses postponed in the south during the first wave compared to other regions (34.8% vs 11.5% vs 22.3%, P‐value <.001). Significantly more patients diagnosed during the second wave had brain metastases and worse performance status compared to the control period. In conclusion, advanced melanoma care in the Netherlands was severely affected by the COVID‐19 pandemic. In the south, the start of systemic treatment for advanced melanoma was more often delayed, and treatment courses were more frequently postponed. During the second wave, patients were diagnosed with poorer patient and tumor characteristics. Longer follow‐up is needed to establish the impact on patient outcomes. courses. During both waves, fewer patients were diagnosed compared to the control groups. During the first wave, time between diagnosis and start of treatment was significantly longer in the southern region compared to other regions (33 vs 9 and 15 days, P-value <.05). Anti-PD-1 courses were postponed in 20.0% vs 3.0% of patients in the first wave compared to the control period. Significantly more patients had courses postponed in the south during the first wave compared to other regions (34.8% vs 11.5% vs 22.3%, P-value <.001). Significantly more patients diagnosed during the second wave had brain metastases and worse performance status compared to the control period. In conclusion, advanced melanoma care in the Netherlands was severely affected by the COVID-19 pandemic. In the south, the start of systemic treatment for advanced melanoma was more often delayed, and treatment courses were more frequently postponed. During the second wave, patients were diagnosed with poorer patient and tumor characteristics. Longer follow-up is needed to establish the impact on patient outcomes. Little is known about the effects of COVID-19 on advanced melanoma care. In this study, the authors examined several quality indicators of care. They observed a worsening in baseline characteristics, longer time between diagnosis and start of treatment and more postponed anti-PD-1 antibody courses with differences between the northern, middle and southern regions. Future studies are necessary to assess the long-term consequences of our observed changes in advanced melanoma care. The SARS-CoV-2 virus has been unprecedentedly disruptive to societies worldwide, infecting over 200 million people, with over 4 million people having died from the virus at the time of writing. 1 Like health care systems in other parts of the world, Dutch healthcare was flooded by the care for COVID-19 patients. Due to the possible exhaustion of the Dutch healthcare system, diagnostics and care for other diagnoses were in some cases postponed or canceled. In addition, oncological care including advanced melanoma care was affected by fear of potential adverse effects of immunosuppressive oncological treatment and checkpoint inhibition on the course of a COVID-19 infection. 2 Research indeed showed cancer patients to be at increased risk from COVID-19 related fatality, 3 although the use of checkpoint inhibitors did not seem to affect this risk as much as initially anticipated. 4 Early studies reported a decrease in melanoma diagnoses during the lockdown and an increase in Breslow thickness in patients diagnosed postlockdown as a result of delaying melanoma care. 5, 6 Yet, effects on systemic melanoma treatment such as treatment delays, discontinuations, or switches during lockdowns are largely unknown. The first case of COVID-19 in the Netherlands was diagnosed on 27 February 2020, in the southern part of the Netherlands. 7 The first COVID-19 wave lasted from March until May 2020 and affected the midsouthern region the heaviest ( Figure 1A,B) 9 For our study, we divided patients in the Netherlands into four groups over time based on the COVID-related pressure on the healthcare system. To determine the healthcare system's burden throughout the country, we used data from the Dutch NICE on the number of hospital beds occupied by COVID-19 patients. 10, 11 The starting point of the first COVID-19 wave, 16 March, was determined based on the moment in time when COVID-19 patients occupied more than 500 hospital beds or more than 200 beds on the intensive care unit (ICU) in the Netherlands. On 24 May 2020, fewer than 200 ICU beds were occupied, marking the endpoint of the first COVID-19 wave. The second COVID-19 wave started on 21 September 2020. December 27 was marked as the endpoint of the second wave in this article, since baseline data registration was complete until this date. patients. The middle region of the Netherlands has the highest population density and was moderately affected by COVID-19 due to the spread from the south. During the first wave, the northern region was the least affected, assisting in care for COVID-19 patients from the south but without many inhabitants from their own region being affected. 12 Patients were assigned to the melanoma center where they were first seen by a medical oncologist. For our study, the dataset cut-off date was 7 April 2021. For the time periods and regions, the following patient and tumor characteristics were described at diagnosis: age, gender (male, female), baseline Eastern Cooperative Oncology Group Performance Status (ECOG PS) (0-1, ≥2), baseline lactate dehydrogenase levels (LDH; normal, 250-500 U/L, >500 U/L), organs with distant metastases (<3 organ sites, ≥3 organ sites involved), brain metastases (none, asymptomatic and symptomatic), liver metastases (yes, no), stage according to American Joint Committee on Cancer (AJCC) 8th edition and BRAF V600 mutational status (wild-type, mutant). We defined several outcome measures to assess the influence of COVID-19 on the diagnosis and treatment of advanced melanoma Baseline patient characteristics were analyzed using descriptive statistics. Pearson's chi-squared test was used to compare categorical variables. The t-test was used to compare numeric data. Comparisons were considered statistically significant for two-sided P-values <.05. Data handling and statistical analyses were performed using R studio (version 4.0.2), 13 packages tidyverse, 14 Table 2 . Only nine courses of either ipilimumab or nivolumab in the induction phase were postponed during the first wave. The number of patients that discontinued a systemic therapy during the first wave did not differ significantly from the control period In our data, we found that 20% of anti-PD-1 courses were postponed. The results of these surveys are in line with our clinical findings that courses of immunotherapy were more often postponed during the COVID-19 pandemic compared to the control period. The first report on the numbers of cancer diagnoses in the Netherlands during the COVID-pandemic was published by Dinmohamed et al. 26 They reported fewer cancer diagnoses between 6 January and 12 April 2020. Uyl-de Groot et al 27 Until now, no study has described the effects of the COVID-19 pandemic on advanced melanoma care. Our study shows the added value of a nationwide quality registry that enables monitoring differences in care between distinct time periods. Data in the DMTR are prospectively registered by data managers, who are trained annually. The online registration survey warns data managers if data are incomplete or inconsistent. All data are checked and confirmed by the patients' treating physicians. Therefore, we consider the data of the DMTR to be of high quality. Wouters have declared no conflicts of interest. Alfonsus J.M. van den Eertwegh has advisory relationships Bristol Myers Squibb Pfizer and Sanofi and has received speaker honoraria from All grants were paid to the institutions. Christian U. Blank has advisory relationships paid to the institute with BMS Research grants Merck-Pfizer. Not related to current work and paid to institute. Geke A.P. Hospers has consultancy/advisory relationships with Amgen, Roche, MSD, BMS, Novartis and Pierre Fabre and has received research grants not related to this article from BMS and Seerave. All grants were paid to the institutions. Astrid A.M. van der Veldt has consultancy relationships paid to the institution with Eisai AbbVie and received honoraria from Novartis and Roche. 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The DMTR was approved by the medical ethical committee and was not deemed subject to the Medical Research Involving Human Subjects Act In compliance with Dutch regulations.