Pediatric Normal Tissue Effects in the Clinic (PENTEC): An International Collaboration to Analyse Normal Tissue Radiation Dose–Volume Response Relationships for Paediatric Cancer Patients

Abstract

With advances in multimodality therapy, childhood cancer cure rates approach 80%. However, both radiotherapy and chemotherapy can cause debilitating or even fatal late adverse events that are critical to understand, mitigate or prevent. QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) identified radiation dose constraints for normal tissues in adults and pointed out the uncertainties in those constraints. The range of adverse events seen in children is different from that in adults, in part due to the vulnerability/characteristics of radiation damage to developing tissues, and in part due to the typical body sites affected by childhood cancer that lead to collateral irradiation of somewhat different normal tissues and organs compared with adults. Many childhood cancer survivors have a long life expectancy and may develop treatment-induced secondary cancers and severe organ/tissue injury 10, 20 or more years after treatment. Collaborative long-term observational studies and clinical research programmes for survivors of paediatric and adolescent cancer provide adverse event data for follow-up periods exceeding 40 years. Data analysis is challenging due to the interaction between therapeutic and developmental variables, the lack of radiation doseevolume data and the fact that most childhood malignancies are managed with combined modality therapy. PENTEC (Pediatric Normal Tissue Effects in the Clinic) is a volunteer research collaboration of more than 150 physicians, medical physicists, mathematical modellers and epidemiologists organised into 18 organ-specific working groups conducting a critical review and synthesis of quantitative data from existing studies aiming to: (1) establish quantitative, evidence-based dose/volume/risk guidelines to inform radiation treatment planning and, in turn, improve outcomes after radiation therapy for childhood cancers; (2) explore the most relevant risk factors for toxicity, including developmental status; (3) describe specific physics and dosimetric issues relevant to paediatric radiotherapy; and (4) propose doseevolume outcome reporting standards for publications on childhood cancer therapy outcomes. The impact of other critical modifiers of normal tissue radiation damage, including chemotherapy, surgery, stem cell transplantation and underlying genetic predispositions are also considered. The aims of the PENTEC reports are to provide clinicians with an analysis of the best available data to make informed decisions regarding radiation therapy normal organ dose constraints for planning childhood cancer treatment, and to define future research priorities.

Modern Radiotherapy for Pediatric Brain Tumors

“…It is a concomitant focus on improving survival while optimizing quality of life that has spawned several ongoing efforts within the pediatric radiation oncology community. These include collaborations across institutions such as through the Pediatric Proton/Photon Consortium Registry (PPCR) [27,28] and Pediatric Normal Tissue Effects in the Clinic (PENTEC) [29], among others. Late effects stemming from RT for pediatric brain tumor patients are dependent on anatomic location of the radiation target and can include neurocognitive dysfunction, neuroendocrine dysfunction, ototoxicity, brainstem toxicity, alopecia, and second malignant and non-malignant neoplasms [3,5,9,[30][31][32][33][34].…”

Dose-Volume Predictors of Radiation Pneumonitis After Lung Stereotactic Body Radiation Therapy (SBRT): Implications for Practice and Trial Design

“…Developing evidence-based dose-volume metrics to generate guidelines for normal tissue sparing is a challenging task assigned to working groups, such as QUANTEC [ 1 ], HyTEC [ 2 , 3 ] or PENTEC [ 5 ]. Selected metrics have to be justified on statistical and mechanistic merits and hypothesis-generating studies taking advantage of detailed patient-specific data provide this justification.…”

“…It has been 10 years since the QUANTEC (Quantitative Analyses of Normal Tissue Effects in the Clinic) reports have been published [ 1 ]. This effort has been followed by forming two more “TEC” working groups, HyTEC (Hypofractionated/High Dose per fraction), which is near completion with a number of papers published [ 2 - 4 ], and PENTEC (Pediatric Normal Tissue Effects in the Clinic), which is currently in progress [ 5 ]. Each working group has been assigned a similar set of tasks: to summarize available literature, to model normal tissue complication probability (NTCP) based upon pooled published data, to provide dosimetric recommendations, and to inform future studies.…”

SIOP PODC–adapted treatment guidelines for craniopharyngioma in low‐ and middle‐income settings

“…59 Normal tissue dose constraints should be guided by QUANTEC/PENTEC. [60][61][62][63][64] A general guide to the treatment of children in LMIC with radiotherapy is available. 65…”