This report assesses the impact of the COVID-19 pandemic on pediatric cancer patients over an 8-week period elapsing from the day of the Italian outbreak (February 20, 2020) to the time of writing (April 15, 2020) in Lombardia region, the epicenter of the pandemic in Italy and one of the worst-hit areas in Europe. During the 8-week period, 155 467 confirmed COVID-19 diagnoses and 19 508 deaths due to the virus were reported in Italy, while Lombardia registered 63 098 positive cases (40% of all Italians affected) and 11 384 deaths. Lombardia is the central region of northern Italy, covering an area of 23 863 km 2 with a population of 10 million (population density 421.6/km 2 ). The region has six pediatric onco-hematology centers.Cancer incidence in the region's population aged 0-18 years is approximately 19/100 000, with 320 new cases expected to occur each year. 1In addition, 40-50% additional patients come from other Italian regions

The rapid spread of coronavirus disease 2019 epidemic in Italy, in particular in the Milan focal point, required drastic measures and led to panic in the population. While in our center we did not change our approach to the treatment of our young patients with cancer, we developed a qualitative survey to assess their perception of the risk and level of stress. The survey showed that a relatively large proportion of young patients felt personally at risk of severe complications. We believe that we need to adequately inform our patients, focusing on hygienic measures and personal protection and prompt reporting of any suspicious symptoms.

Cancers arising from germline DNA mismatch repair deficiency or polymerase proofreading deficiency (MMRD and PPD) in children harbour the highest mutational and microsatellite insertion–deletion (MS-indel) burden in humans. MMRD and PPD cancers are commonly lethal due to the inherent resistance to chemo-irradiation. Although immune checkpoint inhibitors (ICIs) have failed to benefit children in previous studies, we hypothesized that hypermutation caused by MMRD and PPD will improve outcomes following ICI treatment in these patients. Using an international consortium registry study, we report on the ICI treatment of 45 progressive or recurrent tumors from 38 patients. Durable objective responses were observed in most patients, culminating in a 3 year survival of 41.4%. High mutation burden predicted response for ultra-hypermutant cancers (>100 mutations per Mb) enriched for combined MMRD + PPD, while MS-indels predicted response in MMRD tumors with lower mutation burden (10–100 mutations per Mb). Furthermore, both mechanisms were associated with increased immune infiltration even in ‘immunologically cold’ tumors such as gliomas, contributing to the favorable response. Pseudo-progression (flare) was common and was associated with immune activation in the tumor microenvironment and systemically. Furthermore, patients with flare who continued ICI treatment achieved durable responses. This study demonstrates improved survival for patients with tumors not previously known to respond to ICI treatment, including central nervous system and synchronous cancers, and identifies the dual roles of mutation burden and MS-indels in predicting sustained response to immunotherapy.

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This is the first reported prospective national cooperative series of pediatric salivary gland carcinoma patients. Compliance with the TREP recommendations was high. These tumors are rarely managed by pediatric oncologists/surgeons. A broader international cooperation and better networking with otolaryngologists and head-neck surgeons expert on adult salivary gland carcinomas would be advisable.