Cytoreductive Surgery (CRS) and Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) versus palliative chemotherapy in pediatric patients with peritoneal carcinomatosis (<18 years): a baseline report of a living systematic evidence synthesis

Objective: This living systematic review aims to provide a timely, rigorous and continuously updated summary of the evidence available on the effects of CRS and HIPEC on disease free survival, overall survival and quality of life when used as part of the treatment of children with peritoneal carcinomatosis. Methods. Design: This is a baseline synthesis report of a Living Evidence Synthesis (LES) designed and planned following the LE-IHD framework. Based on its conclusions we have activated the evidence monitoring to identify emerging studies that inform on the effectiveness and safety of CRS and HIPEC in the treatment of children with peritoneal carcinomatosis that have been left unresolved by current evidence and require a living evidence approach.Evidence identification, screening, and selection: Automated living searches were performed in relevant databases following the Epistemonikos procedures. Results were incorporated into the Epistemonikos "Living OVerview of Evidence" (L·OVE) platform where two reviewers screened all titles and abstracts supported by automated classifiers that excluded references with a low probability of being relevant. For this baseline report we included one systematic review that evaluated the use of CRS and HIPEC against usual care in children with peritoneal carcinomatosis. We extracted data and assessed the risk of bias of primary studies using appropriate instruments. Measures included were post-operative complications, post-operative mortality, disease free survival at 3 and 5 years, overall survival at 3 and 5 years, overall disease free survival and overall survival at last follow-up and quality of life at different time-points. We applied the GRADE approach to assess the certainty of the evidence found for each outcome. We will continuously monitor the evidence by performing daily searches and monthly screening of the retrieved references. Additionally, each three months we will manually search for ongoing studies in the International Clinical Trials Registry Platform trial registries. The evidence monitoring, including decisions to incorporate evidence and withdraw the question from the living mode will follow the process proposed by the LE-IHD Program Framework and described in our protocol. A living, web-based version of this review will be openly available during the next year at https://livingevidenceihd.com/lesrepo/ .We will resubmit it every time the conclusions change or whenever there are substantial updates.Results: The searches retrieved 7 SRs. Two SRs met the selection criteria and were reviewed in full texts from which an evidence matrix was generated. After assessing the quality of the SRs, we selected the SR of Bywra et al as the basis for this evidence synthesis. Thanks to the recent publication data of the selected SR, we decided not to screen for newly published clinical studies. Variety of study designs and the differences in reporting data, did not allow us to obtain pulled estimates of the effect for any outcome of interest, instead we present narrative descriptions of the results. Among the different type of tumors related to the peritoneal carcinomatosis, DSLRC and mesothelioma were the most common treated types of tumors in the pediatric population. Some data suggests that DSLRC patients obtained the best overall survival in comparison to other types of tumor. Some characteristics, such as the PCI and the presence of extra abdominal metastasis or obtained cytoreduction grade, had an impact in patients’ survival. However, because of the lack of survival data of children with peritoneal carcinomatosis not treated with CRS and HIPEC, we could not assess the impact of CRS and HIPEC in the overall and disease-free survival in those patients. Heterogeneity in the patient's characteristics, but also in the adjuvant treatments, made it difficult to draw conclusions. The certainty of the evidence was rated as very low.Conclusions: The available evidence is affected by clinical and methodological heterogeneity and does not permit drawing conclusions about the effect of the use of CRS and HIPEC in the treatment of children with peritoneal carcinomatosis. Very low certainty evidence suggests that patients with no extra abdominal metastasis, lower PCI value and partial response to chemotherapy, with good cytoreduction results may benefit from CRS and HIPEC. However, very well designed studies assessing the effect of the use of CRS and HIPEC in children with peritoneal carcinomatosis on important outcomes of interest, such as disease free survival, overall survival and quality of life, are needed.