Upfront immunotherapy for synchronous high-grade glioma and B-lymphoma in a pediatric patient with CMMRD syndrome.De Vanssay T1, El Riachy N2, Donze C1,3, Appay R2,4, Scavarda D5,6, Testud B7, Andre N1,3, Revon-Rivière G1,31. Department of Pediatric Hematology, Immunology and Oncology, APHM, La Timone Children's Hospital, Marseille, France. 2. Aix-Marseille Univ, CNRS, INP, Inst Neurophysiopathol, GlioME Team, Marseille, France3. REMAP4KIDS, CNRS, INSERM, CRCM, Aix Marseille University, Marseille, France.4. APHM, CHU Timone, Service d'Anatomie Pathologique et de Neuropathologie, Marseille, France5. Department of Pediatric Neurosurgery. APHM Timone Children’s hospital. Marseille France6. Aix Marseille Univ, INSERM, INS, Inst Neurosci Syst, Marseille, France7. Department of Neuroradiology, APHM, La Timone, Marseille INTRODUCTIONConstitutional Mismatch Repair Deficiency (CMMRD)1, is a rare pediatric cancer predisposition syndrome characterized by early-onset synchronous and metachronous multiorgan tumors.2 It results from bi-allelic inactivation of mismatch repair (MMR) genes, predominantly PMS2 followed by MSH6, MLH1 and MSH2.3 CMMRD predisposes individuals to various malignancies including CNS glioma, gastrointestinal cancer, and hematologic malignancy.4 With an incidence of 1 per million5,6, diagnosing CMMRD is challenging, but early detection is crucial as surveillance significantly impact overall survival (OS). Durno et al. reported a five-year overall survival rate of 90% with systematic surveillance versus 50% without it for asymptomatic cancer.7 Diagnosing CMMRD leads to the use of immunotherapy to treat ultra-hypermutated CMMRD-derived tumors with a Tumor Mutation Burden (TMB) ≥100 mutations/megabase.8 Immune checkpoints inhibitors (ICIs) have shown durable responses in paediatric high-grade glioma arising in CMMRD patients,9, 9 contrasting with their limited efficacy in most other types of pediatric cancers.10 A 2024 international cohort highlighted better outcomes for patients treated with immunotherapy,  regardless of cancer type.3 Consequently, ICIs were approved for advanced paediatric solid tumors in the context of CMMRD, irrespective of histology.9 We report a case of a twelve-year-old CMMRD patient with synchronous high-grade glioma (HGG) and B-cell lymphoma, treated with upfront ICIs alongside with conventional treatment.

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Introduction: Data regarding coronavirus disease 2019 (COVID-19) description are still limited in pediatric oncology. The French society of pediatric oncology (SFCE) has initiated a study to better describe the presentation and evolution of COVID-19 in patients followed in French pediatric oncology and hematology wards. Methods: All patients diagnosed with COVID-19 (polymerase chain reaction [PCR] positive for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], or positive IgM serology, or chest computed tomography scan and clinical signs typical of COVID-19) and followed in a SFCE center were enrolled. Data from medical records were analyzed for all patients enrolled up to the end of May 2020. Results: Data was available for 37 patients. Thirty-one were children under 18 years of age. Nineteen patients were female. Seventeen patients had a solid tumor, 16 had a hematological malignancy and four recently underwent hematopoietic stem cell transplantation (HSCT) for non-oncological conditions. Twenty-eight patients presented symptoms, most often with fever, cough, rhinorrhea and asthenia. Ground-glass opacities were the most frequent radiological finding with abnormalities mostly bilateral and peripherally distributed. Twenty-four patients received chemotherapy a month prior to COVID-19 diagnosis. Most patients did not require hospitalization. Three patients required oxygen at the time of diagnosis. In total, five patients were admitted in an intensive care unit because of COVID-19 and one died from the disease. Conclusion: Children and young adults infected with SARS-CoV-2 and treated for a cancer and/or with a HSCT may be at risk for severe COVID-19 and should be closely monitored. (NCT04433871)

The covid-19 pandemic has forced citizens worldwide to rely on social distancing measures as the main tools to prevent the rapid spreading of the virus (1). In pediatric oncology, there were important initial concerns for immunocompromised patients who were considered to be at higher risk of developing severe form of the disease (2,3). Consequently, potential challenges (2) have been identified and advice given by the principal child cancer organizations (3). Although more experience from countries that have been facing the pandemic are being published, results are inconsistent so far ranging from reassuring in Milano (4), Madrid (5) or New York (6) to worrying in France where 4 out of 33 Covid-19 positive patients required intensive care and 1 death at last follow up (7).Over the last weeks, despite the pandemic we were able to maintain “normal“ care for pediatric cancer patients in our institution, including high-dose chemotherapy followed by peripheral stem cells transplantations, or recruitment in early phase clinical trials. Only follow-up visits have been re-scheduled or switched to remote consultations. After almost 2 months of lock-down and still ongoing social distancing measures, an unexpected challenge has emerged. Inddeed, during that period, as usual we had to break bad news: for diagnosis, for relapse or palliative care. Initially, when breaking bad news, I had the feeling something was going wrong, or at least was not going as usual. Was I doing something wrong? Was stress induced by a high level of anxiety due to the lack of specific information on the real risk for adolescents/children with cancer both among the medical team and or parents affecting the “breaking bad news” process?Why didn’t I take that teenagers in my arms after disclosing her a metastatic relapse and she looked in such a distress?Social distancing!Masks to start with. They are of course a barrier to saliva droplets potentially containing covid-19, but most importantly they are also a barrier to adequately transmit and discriminate emotions just relying on eyes expression, looks…beyond tears. Silent communication with long looks without words can sometimes be enough and better that long talks but do parents and children feel the same when half of the face is covered. I asked about it to one of my patients and he answered“I think can read your eyes” . By increasing the physical space between people to avoid virus spreading, but here again, for physicians and some parents/patients, holding hands, holding shoulders, hugging are important non-verbal elements of communications and help showing compassion.We might break social distancing to break bad news, but if not pre-agreed by the patient or its parents, is it acceptable? Couldn’t it be perceived as an additional threat, contribute to alter intuitive communication which is characterized by broad, shared goals and mutual respect?Breaking bad news while trying to maintain social distancing is an unexpected new challenge associated with Covid-19. We will very likely learn to better communicate, read & share our respective emotions even with masks and physical distancing and sometimes allow ourselves exceptions to social distancing. Meanwhile, this impact shall be further evaluated among all stakeholders: patients, their parents, and physicians and adapted strategies to better cope with it developed.