RAdiotherapy Dose Accumulation Routine (RADAR)-A Novel Dose Accumulation Script With Built-In Uncertainty.

Purpose: To incorporate uncertainty into dose accumulation for reirradiation.

Methods And Materials: The RAdiotherapy Dose Accumulation Routine (RADAR) script for the Eclipse treatment planning system (Varian Medical Systems) is described, and the voxel-wise ellipsoid search algorithm is introduced as a means of incorporating uncertainty. RADAR is first demonstrated on a test patient reirradiated to the spine, illustrating the effect of the uncertainty algorithm.

Reporting Standards for Complication Studies of Radiation Therapy for Pediatric Cancer: Lessons From PENTEC.

The major aim of Pediatric Normal Tissue Effects in the Clinic (PENTEC) was to synthesize quantitative published dose/-volume/toxicity data in pediatric radiation therapy. Such systematic reviews are often challenging because of the lack of standardization and difficulty of reporting outcomes, clinical factors, and treatment details in journal articles. This has clinical consequences: optimization of treatment plans must balance between the risks of toxicity and local failure; counseling patients and their parents requires knowledge of the excess risks encountered after a specific treatment.

A Prospective Study on Deep Inspiration Breath Hold Thoracic Radiation Therapy Guided by Bronchoscopically Implanted Electromagnetic Transponders.

Background: Electromagnetic transponders bronchoscopically implanted near the tumor can be used to monitor deep inspiration breath hold (DIBH) for thoracic radiation therapy (RT). The feasibility and safety of this approach require further study.

Methods: We enrolled patients with primary lung cancer or lung metastases.

Brain and Brain Stem Necrosis After Reirradiation for Recurrent Childhood Primary Central Nervous System Tumors: A PENTEC Comprehensive Review.

Purpose: Reirradiation is increasingly used in children and adolescents/young adults (AYA) with recurrent primary central nervous system tumors. The Pediatric Normal Tissue Effects in the Clinic (PENTEC) reirradiation task force aimed to quantify risks of brain and brain stem necrosis after reirradiation.

Methods And Materials: A systematic literature search using the PubMed and Cochrane databases for peer-reviewed articles from 1975 to 2021 identified 92 studies on reirradiation for recurrent tumors in children/AYA.

Improving Pediatric Normal Tissue Radiation Dose-Response Modeling in Children With Cancer: A PENTEC Initiative.

The development of normal tissue radiation dose-response models for children with cancer has been challenged by many factors, including small sample sizes; the long length of follow-up needed to observe some toxicities; the continuing occurrence of events beyond the time of assessment; the often complex relationship between age at treatment, normal tissue developmental dynamics, and age at assessment; and the need to use retrospective dosimetry. Meta-analyses of published pediatric outcome studies face additional obstacles of incomplete reporting of critical dosimetric, clinical, and statistical information. This report describes general methods used to address some of the pediatric modeling issues.

Clinical and Dosimetric Risk Factors Associated With Radiation-Induced Lung Toxicities After Multiple Courses of Lung Stereotactic Body Radiation Therapy.

Purpose: Data are limited on radiation-induced lung toxicities (RILT) after multiple courses of lung stereotactic body radiation therapy (SBRT). We herein analyze a large cohort of patients to explore the clinical and dosimetric risk factors associated with RILT in such settings.

Methods And Materials: A single institutional database of patients treated with multiple courses of lung SBRT between January 2014 and December 2019 was analyzed.

Stereotactic Body Radiation Therapy for Stage IIA to IIIA Inoperable Non-Small Cell Lung Cancer: A Phase 1 Dose-Escalation Trial.

Purpose: Larger tumors are underrepresented in most prospective trials on stereotactic body radiation therapy (SBRT) for inoperable non-small cell lung cancer (NSCLC). We performed this phase 1 trial to specifically study the maximum tolerated dose (MTD) of SBRT for NSCLC >3 cm.

Methods And Materials: A 3 + 3 dose-escalation design (cohort A) with an expansion cohort at the MTD (cohort B) was used.

Comparison of Risks of Late Effects From Radiation Therapy in Children Versus Adults: Insights From the QUANTEC, HyTEC, and PENTEC Efforts.

Pediatric Normal Tissue Effects in the Clinic (PENTEC) seeks to refine quantitative radiation dose-volume relationships for normal-tissue complication probabilities (NTCPs) in survivors of pediatric cancer. This article summarizes the evolution of PENTEC and compares it with similar adult-focused efforts (eg, Quantitative Analysis of Normal Tissue Effects in the Clinic [QUANTEC] and Hypofractionated Treatment Effects in the Clinic [HyTEC]) with respect to content, oversight, support, scope, and methodology of literature review. It then summarizes key organ-specific findings from PENTEC in an attempt to compare NTCP estimates in children versus adults.

A User's Guide and Summary of Pediatric Normal Tissue Effects in the Clinic (PENTEC): Radiation Dose-Volume Response for Adverse Effects After Childhood Cancer Therapy and Future Directions.

Pediatric Normal Tissue Effects in the Clinic (PENTEC) is an international multidisciplinary effort that aims to summarize normal-tissue toxicity risks based on published dose-volume data from studies of children and adolescents treated with radiation therapy (RT) for cancer. With recognition that children are uniquely vulnerable to treatment-related toxic effects, our mission and challenge was to assemble our group of physicians (radiation and pediatric oncologists, subspecialists), physicists with clinical and modeling expertise, epidemiologists, and other scientists to develop evidence-based radiation dosimetric guidelines, as affected by developmental status and other factors (eg, other cancer therapies and host factors). These quantitative toxicity risk estimates could serve to inform RT planning and thereby improve outcomes.

Exploring published and novel pre-treatment CT and PET radiomics to stratify risk of progression among early-stage non-small cell lung cancer patients treated with stereotactic radiation.

Purpose: Disease progression after definitive stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) occurs in 20-40% of patients. Here, we explored published and novel pre-treatment CT and PET radiomics features to identify patients at risk of progression.

Materials/methods: Published CT and PET features were identified and explored along with 15 other CT and PET features in 408 consecutively treated early-stage NSCLC patients having CT and PET < 3 months pre-SBRT (training/set-aside validation subsets: n = 286/122).

ROE (Radiotherapy Outcomes Estimator): An open-source tool for optimizing radiotherapy prescriptions.

Background And Objectives: Radiotherapy prescriptions currently derive from population-wide guidelines established through large clinical trials. We provide an open-source software tool for patient-specific prescription determination using personalized dose-response curves.

Methods: We developed ROE, a plugin to the Computational Environment for Radiotherapy Research to visualize predicted tumor control and normal tissue complication simultaneously, as a function of prescription dose.

Effects of Radiation Therapy on the Female Reproductive Tract in Childhood Cancer Survivors: A PENTEC Comprehensive Review.

Purpose: The PENTEC (Pediatric Normal Tissue Effects in the Clinic) task force aimed to quantify effects of radiation therapy (RT) dose to the female reproductive organs after treatment for childhood cancer.

Methods And Materials: Relevant studies published 1970 to 2017 were identified systematically through PubMed, Medline, and Cochrane databases with additional articles before 2021 identified by the group. Two large studies reported sufficient data to allow modeling of acute ovarian failure (AOF; loss of function ≤5 year from diagnosis) and premature ovarian insufficiency (POI; loss of function at attained age <40 years) based on maximum dose to least affected ovary.

Creating patient-specific digital phantoms with a longitudinal atlas for evaluating deformable CT-CBCT registration in adaptive lung radiotherapy.

Background: Quality assurance of deformable image registration (DIR) is challenging because the ground truth is often unavailable. In addition, current approaches that rely on artificial transformations do not adequately resemble clinical scenarios encountered in adaptive radiotherapy.

Purpose: We developed an atlas-based method to create a variety of patient-specific serial digital phantoms with CBCT-like image quality to assess the DIR performance for longitudinal CBCT imaging data in adaptive lung radiotherapy.

Cardiac Disease in Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review.

Purpose: Radiation therapy (RT) is an essential component in the treatment of many pediatric malignancies. Thoracic RT may expose the heart to radiation dose and thereby increase the risk of late cardiac disease. This comprehensive review from the Pediatric Normal Tissue Effects in the Clinic (PENTEC) initiative focused on late cardiac disease in survivors of childhood cancer treated with RT.

Physics Considerations for Evaluation of Dose for Dose-Response Models of Pediatric Late Effects From Radiation Therapy: A PENTEC Introductory Review.

Purpose: We describe the methods used to estimate the accuracy of dosimetric data found in literature sources used to construct the Pediatric Normal Tissue Effects in the Clinic (PENTEC) dose-response models, summarize these findings of each organ-specific task force, describe some of the dosimetric challenges and the extent to which these efforts affected the final modeling results, and provide guidance on the interpretation of the dose-response results given the various dosimetric uncertainties.

Methods And Materials: Each of the PENTEC task force medical physicists reviewed all the journal articles used for dose-response modeling to identify, categorize, and quantify dosimetric uncertainties. These uncertainties fell into 6 broad categories.

Phase 1 Dose Escalation Study of SBRT Using 3 Fractions for Locally Advanced Pancreatic Cancer.

Purpose: The optimal dose and fractionation of stereotactic body radiation therapy (SBRT) for locally advanced pancreatic cancer (LAPC) have not been defined. Single-fraction SBRT was associated with more gastrointestinal toxicity, so 5-fraction regimens have become more commonly employed. We aimed to determine the safety and maximally tolerated dose of 3-fraction SBRT for LAPC.

Radiation-induced inferior brachial plexopathy after stereotactic body radiotherapy: Pooled analyses of risks.

Introduction: Radiation-induced brachial plexopathy (RIBP), resulting in symptomatic motor or sensory deficits of the upper extremity, is a risk after exposure of the brachial plexus to therapeutic doses of radiation. We sought to model dosimetric factors associated with risks of RIBP after stereotactic body radiotherapy (SBRT).

Methods: From a prior systematic review, 4 studies were identified that included individual patient data amenable to normal tissue complication probability (NTCP) modelling after SBRT for apical lung tumors.

Modeling clinical outcomes in radiotherapy: NTCP, TCP and the "TECs".

Radiation therapy is a double-edged sword which damages both tumor and normal cells. Achieving treatments with high tumor control probability (TCP) yet low normal tissue complication probability (NTCP) is often a struggle because we rarely have a unified understanding of the dosimetric and clinical correlates of the desired outcomes. I am fortunate to have participated in some of these struggles, including analyzing and using in-house data and being involved in the AAPM and ASTRO "TEC" projects-QUANTEC (Quantitatie Analysis of Normal Tissue Effects in the Clinic), HyTEC (Hypofractionated Treatment Effects in the Clinic) and PENTEC (Pediatric Normal Tissue Effects in the Clinic).

Association of cardiac calcium burden with overall survival after radiotherapy for non-small cell lung cancer.

Background And Purpose: Coronary calcifications are associated with coronary artery disease in patients undergoing radiotherapy (RT) for non-small cell lung cancer (NSCLC). We quantified calcifications in the coronary arteries and aorta and investigated their relationship with overall survival (OS) in patients treated with definitive RT (Def-RT) or post-operative RT (PORT).

Materials And Methods: We analyzed 263 NSCLC patients treated from 2004 to 2017.

Hypofractionated Stereotactic Radiation Therapy Dosimetric Tolerances for the Inferior Aspect of the Brachial Plexus: A Systematic Review.

We sought to systematically review and summarize dosimetric factors associated with radiation-induced brachial plexopathy (RIBP) after stereotactic body radiation therapy (SBRT) or hypofractionated image guided radiation therapy (HIGRT). From published studies identified from searches of PubMed and Embase databases, data quantifying risks of RIBP after 1- to 10-fraction SBRT/HIGRT were extracted and summarized. Published studies have reported <10% risks of RIBP with maximum doses (D) to the inferior aspect of the brachial plexus of 32 Gy in 5 fractions and 25 Gy in 3 fractions.

RMSim: controlled respiratory motion simulation on static patient scans.

This work aims to generate realistic anatomical deformations from static patient scans. Specifically, we present a method to generate these deformations/augmentations via deep learning driven respiratory motion simulation that provides the ground truth for validating deformable image registration (DIR) algorithms and driving more accurate deep learning based DIR.We present a novel 3D Seq2Seq deep learning respiratory motion simulator (RMSim) that learns from 4D-CT images and predicts future breathing phases given a static CT image.

A Phase 1 Safety Study of Avelumab Plus Stereotactic Body Radiation Therapy in Malignant Pleural Mesothelioma.

Introduction: Single-agent monoclonal antibody therapy against programmed death-ligand 1 (PD-L1) has modest effects in malignant pleural mesothelioma. Radiation therapy can enhance the antitumor effects of immunotherapy. Nevertheless, the safety of combining anti-PD-L1 therapy with stereotactic body radiation therapy (SBRT) is unknown.

Osteoradionecrosis of the Jaw Following Proton Radiation Therapy for Patients With Head and Neck Cancer.

Importance: Proton radiation therapy (PRT) has reduced radiation-induced toxic effects, such as mucositis and xerostomia, over conventional photon radiation therapy, leading to significantly improved quality of life in patients with head and neck cancers. However, the prevalence of osteoradionecrosis (ORN) of the jaw following PRT in these patients is less clear.

Objective: To report the prevalence and clinical characteristics of ORN in patients with oral and oropharyngeal cancer (OOPC) treated with PRT.