SummaryBackgroundIncomplete surgical resection of medulloblastoma is controversially considered a marker of high-risk disease; driving aggressive surgical resections, “second-look” surgeries, and/or intensified chemoradiotherapy. All prior publications evaluating the clinical importance of extent of resection (EOR) failed to account for molecular subgroup. We analysed the prognostic value of EOR across 787 medulloblastoma samples in a subgroup-specific manner.MethodsWe retrospectively identified patients from Medulloblastoma Advanced Genomics International Consortium (MAGIC) centres with a histological diagnosis of medulloblastoma and complete extent of resection and survival data. Specimens were collected from 35 international institutions. Medulloblastoma subgroup affiliation was determined using nanoString gene expression profiling on frozen or formalin-fixed paraffin-embedded tissues. Extent of resection (EOR) based on post-operative imaging was classified as gross total (GTR), near total (NTR, <1·5cm2), or subtotal (STR, ≥ 1·5cm2). Overall survival (OS) and progression-free survival (PFS) multivariable analyses including subgroup, age, metastatic status, geographical location of therapy (North America/Australia vs world), and adjuvant therapy regimen were performed. The primary endpoint was the impact of surgical EOR by molecular subgroup and other clinical variables on OS and PFS.Findings787 medulloblastoma patients (86 WNT, 242 SHH, 163 Group 3, and 296 Group 4) were included in a multivariable Cox model of PFS and OS. The marked benefit of EOR in the overall cohort was greatly attenuated after including molecular subgroup in the multivariable analysis. There was an observed PFS benefit of GTR over STR (hazard ration [HR] 1·45, 95% CI; 1·07–1·96, p=0·02) but there was no observed PFS or OS benefit of GTR over NTR (HR 1·05, 0·71–1·53, p=0·82 and HR 1·14, 0·75–1·72, p=0.55). There was no statistically significant survival benefit to greater EOR for patients with WNT, SHH, or Group 3 patients (HR 1·03, 0·67–1·58, p=0·9 for STR vs. GTR). There was a PFS benefit for GTR over STR in patients with Group 4 medulloblastoma (HR1·97, 1·22–3·17, p=0·01), particularly those with metastatic disease (HR 2·22, 1–4·93, p=0·05). A nomogram based on this multivariable cox proportional hazards model shows the comparably smaller impact of EOR on relative risk for PFS and OS than subgroup affiliation, metastatic status, radiation dose, and adjuvant chemotherapy.InterpretationThe prognostic benefit of EOR for patients with medulloblastoma is attenuated after accounting for molecular subgroup affiliation. Although maximal safe surgical resection should remain the standard of care, surgical removal of small residual portions of medulloblastoma is not recommended when the likelihood of neurological morbidity is high as there is no definitive benefit to GTR over NTR. Our results suggest a re-evaluation of the long-term implications of intensified craniospinal irradiation (36 Gy) in children with small residual portions of medullobla...

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Somatotropin deficiency is the most common endocrinopathy in childhood cancer survivors. However, studies of final height in these patients treated with somatotropin are limited. Thus, this study was performed to examine their growth outcomes. Methods: A retrospective analysis was performed, including all childhood cancer survivors treated with somatotropin in a pediatric endocrinology department, between 1988 and 2016. Statistical analysis was performed. Results: Twenty-seven cancer survivors with a median of 5.5 years of age at diagnosis were included; 16 (59.3%) had central nervous system cancer; 19 (70.4%) were submitted to radiotherapy. Concomitant endocrinopathies existed in 14 (51.9%). Somatotropin treatment was started at a median age of 11.13 years with a median duration of 4.1 years. The initial height was −2.30 standard deviation score (SDS) and increased to −1.81 SDS by 1 year, −1.68 SDS by 2 years, and −1.56 SDS by 3 years under somatotropin treatment. There were significant differences in height between the beginning and by 1 year (p<0.001), by 1 and 2 years (p=0.006) and between initial and the end of treatment (p=0.022). However, the adult height was significantly lower than the midparental height (p=0.011), with no differences associated with gender, group of cancer, radiotherapy, concomitant endocrinopathies, age or pubertal stage at beginning. Conclusion:We concluded that the improvement of linear growth was significant, mainly in the first year of treatment, but these patients did not achieve their genetic potential for height. Physicians must be aware and search for somatotropin deficiency in cancer survivors and treatment should be started as soon as possible. R E S U M O o impacto na estatura da somatotropina em sobreviventes oncológicosIntrodução: A deficiência de somatotropina é a endocrinopatia mais comum em sobreviventes de cancro em idade pediátrica. No entanto, estudos sobre a estatura final destes doentes tratados com somatotropina são escassos, pelo que o objetivo deste estudo foi avaliar o crescimento destes doentes. Métodos: Foi realizada uma análise retrospetiva, incluindo todos os sobreviventes de cancro em idade pediátrica tratados com somatotropina numa unidade de endocrinologia pediátrica, entre 1988 e 2016. Foi realizada a análise estatística dos dados. Palavras-chave:Desenvolvimento da Criança/efeitos dos fármacos; Estatura/efeitos dos fármacos; Hormona do Crescimento/uso terapêutico; Neoplasias/complicações; Sobreviventes.

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