Wolden, Suzanne L.

ABSTRACT Pediatric radiation therapy presents unique challenges compared to adult treatments, including those of immobilization, potential need for sedation, and the critical importance of accurate, reproducible positioning. Additionally, heightened attention to imaging doses is necessary to minimize long‐term toxicity in survivors. Many of these challenges must be addressed during the process of simulation. This report provides guidelines for pediatric radiotherapy simulation from the Children's Oncology Group. These guidelines cover all anatomic sites and include recommendations for photon and proton therapies, as well as specialized procedures such as stereotactic body radiation therapy, brachytherapy, and total body irradiation. These guidelines are presented as recommendations rather than prescriptive standards as the practice will vary depending on patient age, diagnosis, clinical judgment, and institutional resources.

Abstract Purpose: Embryonal tumor with multilayered rosettes (ETMR) is a rare pediatric CNS embryonal tumor with poor survival. The Pediatric Proton/Photon Consortium Registry (PPCR) was queried for outcomes data from prospectively consenting pediatric patients with ETMR treated with proton radiation therapy (RT). Methods: 20 patients (2013-2021) at 9 institutions had ETMR; 2 with prior RT were excluded from statistical analyses (PPCR ETMR, N=18). Overall Survival (OS) and Event Free Survival (EFS) analyses were performed using the Kaplan-Meier method and log-rank values. Median follow-up was calculated using the reverse Kaplan-Meier method. Results: Median age at RT was 3.0 years (1.7-12.2); median follow-up was 55.5 months (2.6-119.4). 8 patients (44%) expired and 6 patients (33%) are surviving ≥55 months. 11 (61%) patients received systemic therapy with stem cell support. The majority (89%) had focal RT, while 2 patients received craniospinal irradiation (CSI). 4-year OS and EFS were 59.6% and 54.2%, respectively. Local control (LC) at 4 years was 81%. No differences in OS or EFS were observed for receipt of systemic therapy with stem cell support (p=0.361, p=0.57), progression prior to RT (p=0.127, p=0.18), or surgery to RT ≥200 days (p=0.35, p=0.254). Symptomatic radionecrosis was not reported. Conclusion: Focal proton RT provided effective local control as part of multimodality therapy for ETMR, with encouraging survival for this rare and often infant age tumor. Outcomes for CSI were limited to 2 patients treated upfront, and 1 patient receiving salvage CSI for disseminated relapse after focal RT who is surviving >1 year. Trial: DFCI protocol 12-103, clinicaltrials.gov NCT01696721, date of registration 9/27/2012

AbstractRadiation oncology is an integral part of the multidisciplinary team caring for children with cancer. The primary goal of our committee is to enable the delivery of the safest dose of radiation therapy (RT) with the maximal potential for cure, and to minimize toxicity in children by delivering lower doses to normal tissues using advanced technologies like intensity‐modulated RT (IMRT) and proton therapy. We provide mentorship for y ators and are actively involved in educating the global radiation oncology community. We are leaders in the effort to discover novel radiosensitizers, radioprotectors, and advanced RT technologies that could help improve outcomes of children with cancer.

AbstractBackgroundPositron emission tomography (PET)‐based measures of baseline total‐body tumor burden may improve risk stratification in intermediate‐risk Hodgkin lymphoma (HL).Materials and methodsEvaluable patients were identified from a cohort treated homogeneously with the same combined modality regimen on the Children's Oncology Group AHOD0031 study. Eligible patients had high‐quality baseline PET scans. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were each measured based on 15 thresholds for every patient. Univariate and multivariable Cox regression and Kaplan–Meier survival analyses assessed for an association of MTV and TLG with event‐free survival (EFS).ResultsFrom the AHOD0031 cohort (n = 1712), 86 patients were identified who (i) were treated with four cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide (ABVE‐PC) chemotherapy followed by involved field radiotherapy, and (ii) had a baseline PET scan that was amenable to quantitative analysis. Based on univariate Cox regression analysis, six PET‐derived parameters were significantly associated with EFS. For each of these, Kaplan–Meier analyses and the log‐rank test were used to compare patients with highest tumor burden (i.e., highest 15%) to the remainder of the cohort. EFS was significantly associated with all six PET parameters (all p < .029). In a multivariable model controlling for important covariates including disease bulk and response to chemotherapy, MTV2BP was significantly associated with EFS (p = .012).ConclusionMultiple baseline PET‐derived volumetric parameters were associated with EFS. MTV2BP was highly associated with EFS when controlling for disease bulk and response to chemotherapy. Incorporation of baseline MTV into risk‐based treatment algorithms may improve outcomes in intermediate‐risk HL.

AbstractRadiosurgery and brachytherapy are potentially useful treatment techniques that are sparingly applied in pediatric oncology. They are often used in the setting of reirradiation for recurrent or metastatic tumors. Reirradiation in children with recurrent tumors is complicated by the tolerance of critical organs and the potential risks for overall long‐term dose‐dependent complications. We review the current literature available in support of reirradiation and the use of radiosurgery and brachytherapy in pediatric patients.

Background Most children with intermediate‐risk rhabdomyosarcoma (RMS) have gross disease (group III) at the initiation of chemotherapy. Delayed primary excision (DPE) after induction chemotherapy allows for a reduction in adjuvant radiation dose, but with the risk of potential surgical morbidity. The objectives of this study were to compare outcomes in children with group III RMS who did and did not undergo DPE and to assess surgical morbidity. Methods The study included 369 patients who had clinical group III RMS at sites amenable to DPE from intermediate‐risk Children's Oncology Group studies D9803 (encouraged DPE) and ARST0531 (discouraged DPE). Results The primary tumor site was bladder/prostate (136 patients; 37%), extremity (97 patients; 26%), trunk (24 patients; 7%), retroperitoneum (91 patients; 25%), or intrathoracic/perineum/perianal (21 patients; 6%). In total, 112 patients (53.9%) underwent DPE in D9803, and 26 patients (16.2%) underwent DPE in ARST0531 ( P < .001), with loss of vital organ or function in 30 of 138 patients (22%). DPE allowed for a reduced radiation dose in 110 of 135 patients (81%; 51% were reduced to 36 Gy, and 30% were reduced to 42 Gy). Patients who underwent DPE had improved unadjusted overall survival ( P = .013). In adjusted regression analysis, the risk of death (hazard ratio, 0.71; 95% CI 0.43‐1.16) was similar for patients who did and did not undergo DPE and was improved for the subset of patients who had tumors of the trunk and retroperitoneum (hazard ratio, 0.44; 95% CI, 0.20‐0.97). Conclusions Children with group III RMS have equivalent or improved outcomes with DPE and can receive a decreased radiation dose for definitive local control. The choice of local control modality should weigh the potential morbidity of surgery versus that of higher dose irradiation.

AbstractTo examine the educational background, clinical practice, and preferences regarding continuing medical education (CME) among radiation oncologists who attended the 2019 meeting of the Pediatric Radiation Oncology Society (PROS), a survey consisting of 20 questions was distributed asking for demographic and educational background, clinical practice, and preferences regarding pediatric radiation oncology CME. Of 188 participants, 130 (69.2%) returned the questionnaire. More than 80% reported access to CT simulation, three‐dimensional radiotherapy, and general anesthesia while <30% had access to intraoperative radiotherapy, proton, and heavy particle therapy. After residency, 12.1% did further training in pediatric radiation oncology. When asked about further training in pediatrics after residency, 88.8% answered that there should be a formal training program beyond residency in order to treat children. More than 75% acquired knowledge in pediatric radiation oncology through journals, books, live meetings, and tumor boards. The results of this survey may help Pediatric Radiation Oncology Society (PROS) in creating guidelines and recommendations for improvement in pediatric radiation oncology training and practice support as well as the development of CME activities most likely to benefit practitioners.

AbstractThis report by the Radiation Oncology Discipline of Children's Oncology Group (COG) describes the practice patterns of pediatric image‐guided radiotherapy (IGRT) based on a member survey and provides practice recommendations accordingly. The survey comprised of 11 vignettes asking clinicians about their recommended treatment modalities, IGRT preferences, and frequency of in‐room verification. Technical questions asked physicists about imaging protocols, dose reduction, setup correction, and adaptive therapy. In this report, the COG Radiation Oncology Discipline provides an IGRT modality/frequency decision tree and the expert guidelines for the practice of ionizing image guidance in pediatric radiotherapy patients.

Abstract The International Soft‐Tissue Sarcoma Consortium (INSTRuCT) was founded as an international collaboration between different pediatric soft‐tissue sarcoma cooperative groups (Children's Oncology Group, European Pediatric Soft‐Tissue Sarcoma Group, and Cooperative Weichteilsarkom Studiengruppe). Besides other tasks, a major goal of INSTRuCT is to develop consensus expert opinions for best clinical treatment. This consensus paper for patients with rhabdomyosarcoma of the female genital tract (FGU‐RMS) provides treatment recommendations for local treatment, long‐term follow‐up, and fertility preservation. Therefore, a review of the current literature was combined with recommendations of the treatment protocols of the appropriate clinical trials. Additionally, opinions of international FGU‐RMS experts were incorporated into recommendations. Results were that the prognosis of FGU‐RMS is favorable with an excellent response to chemotherapy. Initial complete surgical resection is not indicated, but diagnosis should be established properly. In patients with tumors localized at the vagina or cervix demonstrating incomplete response after induction chemotherapy, local radiotherapy (brachytherapy) should be carried out. In patients with persistent tumors at the corpus uteri, hysterectomy should be performed. Fertility preservation should be considered in all patients. In conclusion, for the first time, an international consensus for the treatment of FGU‐RMS patients could be achieved, which will help to harmonize the treatment of these patients in different study groups.

Background The International Soft Tissue Sarcoma Consortium (INSTRuCT) was founded as an international collaboration between different pediatric soft tissue sarcoma cooperative groups (COG, EpSSG, CWS). Besides other tasks, a major goal of the INSTRuCT is to develop consensus expert opinions for best clinical treatment. This consensus paper for patients with rhabdomyosarcoma of the female genital tract (FGU-RMS) provides treatment recommendations for local treatment, long term follow up and fertility preservation. Methods Review of the current literature was combined with recommendations of the treatment protocols of the appropriate clinical trials. Additionally, opinions of international FGU-RMS experts were incorporated into recommendations. Results The prognosis of FGU-RMS is favorable with an excellent response to chemotherapy. Initial complete surgical resection is not indicated, but diagnosis should be established properly. In patients with tumors localized at the vagina or cervix demonstrating incomplete response after induction chemotherapy, local radiotherapy (brachytherapy) should be carried out. In patients with persistent tumors at the corpus uteri, hysterectomy should be performed. Fertility preservation should be considered in all patients. Conclusion For the first time, an international consensus for the treatment of FGU-RMS patients could be achieved, which will help to harmonize the treatment in different study groups.