Purpose:ASTRO's 2018 guidelines for hypofractionated whole-breast irradiation (HF WBI) recommend limiting high-dose regions to improve dose homogeneity and minimize toxicity. However, correlation of these guidelines with clinical outcomes remains limited. This study investigates the relationship between dose-volume parameters and acute toxicities including pain, erythema, edema and moist desquamation in patients treated with HF WBI in accordance with ASTRO 2018 guidelines. Methods and Materials:We retrospectively reviewed patients treated from 2018 to 2023 with HF WBI (42.56 Gy in 16 fractions or 40.05 Gy in 15 fractions) between 2018 and 2023 using 3-dimensional conformal field-in-field planning. All plans adhered to ASTRO constraints (V105% < 200 cm3; V107% < 2 cm3). Acute toxicities were prospectively scored using the Common Terminology Criteria for Adverse Events V5.0 at weekly on-treatment visits (OTVs) and at 1 month follow-up. Logistic regression analyses identified predictors of grade ≥ 2 toxicities. Results:600 patients were treated with HF WBI. Of those patients, 82.3% received a dose of 42.56 Gy in 16 fractions, whereas the remaining received 40.05 Gy in 15 fractions. Three-dimensional field-in-field planning was used in all patients and 73.7% received a boost. Moderate-to-severe pain (grade ≥ 2) occurred in 29.7% of patients during treatment despite compliance with ASTRO guidelines. In contrast, grade ≥ 2 erythema, edema, and moist desquamation were observed in <5% of patients. Multivariate analysis identified V105 % (cm3) ≥ 50 cm3, V105 % (%) ≥ 5% and body mass index ≥ 30 as independent predictors of grade ≥ 2 pain, which decreased by 30% when V105 % (cm3) < 50 cm3 and by 18.5% when V105 % (%) < 5%. Conclusions:Although skin related toxicities were infrequent and largely resolved by 1 month, pain remained a prevalent side effect of HF WBI. These findings suggest that ASTRO's current V105% thresholds may be too permissive for pain mitigation. Stricter limits of V105% (cm3) < 50 cm3 and V105% (%) < 5% may better protect patients from treatment-related discomfort and warrant consideration in future guideline updates.

Purpose:While the effects of prostate radiation therapy on erectile function are well documented, data on receptive anal intercourse (RAI) remain sparse, despite its prevalence among gay and bisexual men. This study investigated associations between radiation dose to RAI functional anatomy and problematic RAI to identify preliminary, clinically meaningful dosimetric parameters. Methods and Materials:Fourteen prostate cancer survivors who engaged in RAI and completed Patient-Reported Outcomes Measurement Information System questionnaires were retrospectively evaluated. RAI functional anatomy (anal canal, levator ani, erectile tissues, neurovascular bundles, and internal pudendal arteries [IPAs]) was delineated, and dosimetric parameters were extracted. Dose-outcome relationships were assessed using Spearman's correlation (ρ) and logistic regression. Results:Anal canal maximum dose (Dmax; minimum dose to the hottest 0.03 cm3) and minimum dose tot he hottest 2 cm3 (D2cm3) were strongly associated with orgasm ability (ρ = -0.63), while mean dose (Dmean) showed a moderate association (ρ = -0.57); all anal canal parameters were moderately associated with orgasm pleasure (ρ range, -0.50 to -0.56). Levator ani Dmean and D2cm3 were moderately associated with orgasm ability and pleasure (ρ range, -0.48 to -0.58). Erectile tissue high-dose parameters were strongly associated with orgasm ability (ρ range, -0.61 to -0.68) but not with orgasm pleasure (ρ range, -0.39 to -0.46). IPA Dmax was moderately associated with orgasm ability (ρ = -0.52) and pleasure (ρ = -0.55). Neurovascular bundle dosimetry and anal pain showed no evidence of association. Exploratory dose thresholds corresponding to a 10% probability of dysfunction, in equivalent doses in 2 Gy fractions with an α/β ratio of 3 (EQD2[3]), were identified for the anal canal (Dmax, 40; Dmean, 9; D2cm3, 4), levator ani (Dmean, 31), erectile tissues (Dmax, 20; Dmean, 5), and IPA (Dmax, 35). Conclusions:This study provides the first evidence on the association between radiation dose to RAI functional anatomy and problematic RAI. While exploratory, these results may help guide future studies and inform counseling.

Purpose While the effects of prostate radiotherapy on erectile function are well documented, data on receptive anal intercourse (RAI) remain sparse, despite its prevalence among gay and bisexual men. This study investigated associations between radiation dose to RAI functional anatomy and problematic RAI to identify preliminary, clinically meaningful dosimetric parameters. Methods Fourteen prostate cancer survivors who engaged in RAI and completed PROMIS questionnaires were retrospectively evaluated. RAI functional anatomy (anal canal, levator ani, erectile tissues, neurovascular bundles [NVB], internal pudendal arteries [IPA]) was delineated, and dosimetric parameters were extracted. Dose-outcome relationships were assessed using Spearman's correlation (ρ) and logistic regression. Results Anal canal Dmax and D2cc were strongly associated with orgasm ability (ρ=-0.63), while Dmean showed a moderate association (ρ=-0.57); all anal canal parameters were moderately associated with orgasm pleasure (ρ range, -0.50 to -0.56). Levator ani Dmean and D2cc were moderately associated with orgasm ability and pleasure (ρ range, -0.48 to -0.58). Erectile tissue high-dose parameters were strongly associated with orgasm ability (ρ range, -0.61 to -0.68) but not with orgasm pleasure (ρ range, -0.39 to -0.46). IPA Dmax was moderately associated with orgasm ability (ρ=-0.52) and pleasure (ρ=-0.55). NVB dosimetry and anal pain showed no evidence of association. Exploratory dose thresholds (Gy EQD2(3)) corresponding to 10% probability of dysfunction were identified—anal canal (Dmax: 40, Dmean: 9, D2cc: 4), levator ani (Dmean: 31), erectile tissues (Dmax: 20, Dmean: 5), and IPA (Dmax: 35). Conclusion This study provides the first evidence on the association between radiation dose to RAI functional anatomy and problematic RAI. While exploratory, these results may help guide future studies and inform counseling.

Purpose:The relative biological effectiveness (RBE) of tumor control for proton beam therapy (PBT) compared to photon radiotherapy (RT) is typically assumed to be independent of fractionation. To test this, we modeled published PBT outcome results for early-stage non-small cell lung cancer (NSCLC) treatments across a range of fractionation schedules. Materials and Methods:All published and analyzable cohorts were included (399 patients, 413 treated lesions). Two models were used to fit the data: a previously published tumor simulation model that fits photon RT results of NSCLC across all fractionation regimes and the Fowler LQ model with a kick-off time term. The treatment effect of each cohort was referenced to the photon equivalent dose through mechanistic model simulations in a 2 Gy/weekday scenario, with radiobiological parameters determined to simultaneously best-fit all fractionation results. The tumor control RBE of each published treatment schedule, compared to the modeled photon RT effect of the same schedule, was then estimated. Results:For cohorts whose treatments lasted less than three weeks (i.e., 12 fractions or less), the RBE of PBT was in the range of 1.08 to 1.11. However, for fractionated treatments stretching over four weeks or more (20-25 fractions), the relative effectiveness was much lower, with RBEs in the range of 0.82-0.89. This conclusion was unchanged using the simpler Fowler LQ + time model. Conclusions:The proton RBE for hypo-fractionated schedules was 20-30% higher than for conventional schedules. The derived radiobiological parameters of PBT differ significantly from those of photon RT, indicating that PBT is influenced differentially by radiobiological mechanisms which require further investigation.

INTRODUCTION:Despite the increasing frequency of reirradiation (reRT) in cancer treatment, a critical lack of reliable dose constraint data remains. This study addresses this gap by collating current reRT constraints used in clinical practice across multiple centers, facilitating the development of more consistent and safer reRT guidelines. MATERIALS AND METHODS:A comprehensive survey collected data on reRT patient numbers, dose constraints, sources, and dose summation methods for 30 OARs. Information also included PRV margins, tissue recovery factors (TRF) with time intervals, α/β values, near-Dmax definitions, and dose constraints in EQD2Gy for first and reRT courses. The relative difference (XreRT) between cumulative reRT and first course constraints was calculated. Constraints with data from at least 7 centers were included for further analysis. RESULTS:A median of 6 % of treatments in 17 participating centers were reRT. Most centers derived reRT constraints from the literature (81 %) or first course constraints (68 %). In total 209 cumulative near-Dmax values for 19 OARs fulfilled n ≥ 7, yielding a median inter-center variation of 21 % (IQR). While α/β values were relatively consistent, substantial variations were seen in near-Dmax volume definition, TRF, and PRV margins. The median XreRT was 26 %, primarily attributed to the TRF which had a median value of 23 %. CONCLUSIONS:This multi-centre survey identified a concerning median inter-centre variation of 21 % in cumulative reRT dose constraints, indicating substantial heterogeneity in current clinical practices. Further prospective studies with rigorous and standardized dose reporting are essential to refine reRT guidelines, enhancing patient safety and treatment efficacy.

Purpose Spine stereotactic body radiation therapy (SBRT) outperforms conventional radiation therapy in preventing local failure (LF). Data comparing dose-fractionation schemes on the likelihood of LF and vertebral compression fracture (VCF) are limited. Methods and Materials This is a retrospective cohort study of 1838 patients (2702 lesions) treated between 2014 and 2023 at a single institution with de novo spine SBRT. LF was defined as progressive disease on magnetic resonance imaging. VCF was defined as progressive or new fracture on magnetic resonance imaging without LF. Death was considered a competing risk. Results Median follow-up after SBRT for surviving patients was 25 months (IQR 13-43 months). Eleven hundred ninety-seven lesions (44%) received 27 Gy in 3 fractions, 931 (34%) received 30 Gy in 3 fractions, and 574 lesions (21%) received 24 Gy in 1 fraction. Three hundred nine treatment courses involved separation surgery (11%), and 311 lesions (11%) were epidural spinal cord compression score 2 to 3. For lesions treated with 24 Gy in 1 fraction, 30 Gy in 3 fractions, and 27 Gy in 3 fractions, 2-year LF rates (95% CI) were 7% (5%-9%), 11% (9%-13%), and 17% (15%-20%), respectively (P < .001). Two-year VCF rates (95% CI) requiring stabilization were 10% (8%-13%; 24 Gy in 1 fraction), 2% (1%-3%; 27 Gy in 3 fractions), and 3% (2%-5%; 30 Gy in 3 fractions) (P < .001). For the 3-fraction regimens specifically, 30 Gy was associated with a higher overall VCF rate (P = .022) and lower LF rate (P < .001), but there was no significant difference in the risk of VCF requiring intervention (P = .15). Univariable and multivariable regression revealed histologic-based differences in LF: 2-year LF rates were 8.6% (95% CI, 6.4%-11%) for class A lesions (prostate and breast cancers), 26% (95% CI, 20%-32%) for class C lesions (cholangio-, hepatocellular, and colorectal carcinoma), and 13% (95% CI, 12%-15%) for class B lesions (other histologies) (P < .001). For class B to C, epidural spinal cord compression 2 to 3 lesions (n = 261), surgery plus SBRT reduced LF compared to SBRT alone (7.9 vs 20% at 2 years, P = .051), though this did not reach statistical significance. Conclusions The preferred hypofractionated SBRT regimen—even for class A histologies—is 30 Gy in 3 fractions, offering superior local control with similar risk of VCF requiring intervention, compared to 27 Gy. For class B to C lesions with high-grade epidural disease, separation surgery prior to SBRT may improve local control.

We dedicate this Pediatric Normal Tissue Effects in the Clinic (PENTEC) special issue of our premier journal to all the children and their loved ones who have been afflicted by cancer. We mourn those who have succumbed, celebrate those who survived, and strive to ease the journey for all who might be affected by our therapies.

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. Grade 2 or higher (G2+) RILT after the last course of SBRT was the primary endpoint. Composite plans were generated with advanced algorithms including deformable registration and equivalent dose adjustment. Logistic regression analyses were performed to examine correlations between patient or treatment factors including dosimetry and G2+ RILT. Risk stratification of patients and lung constraints based on acceptable normal tissue complication probability were calculated based on risk factors identified. Results: Among 110 eligible patients (56 female and 54 male), there were 64 synchronous (58.2%; defined as 2 courses of SBRT delivered within 30 days) and 46 metachronous (41.8%) courses of SBRT. The composite median lung V20, lung V5, and mean lung dose were 9.9% (interquartile range [IQR], 7.3%-12.4%), 32.2% (IQR, 25.5%-40.1%), and 7.0 Gy (IQR, 5.5 Gy-8.6 Gy), respectively. With a median follow-up of 21.1 months, 30 patients (27.3%) experienced G2+ RILT. Five patients (4.5%) developed G3 RILT, and 1 patient (0.9%) developed G4 RILT, and no patients developed G5 RILT. On multivariable regression analysis, female sex (odds ratio [OR], 4.35; 95% CI, 1.49%-14.3%; P = .01), synchronous SBRT (OR, 8.78; 95% CI, 2.27%-47.8%; P = .004), prior G2+ RILT (OR, 29.8; 95% CI, 2.93%-437%; P = .007) and higher composite lung V20 (OR, 1.18; 95% CI, 1.02%-1.38%; P = .030) were associated with significantly higher likelihood of G2+ RILT. Conclusions: Our data suggest an acceptable incidence of G2+ RILT after multiple courses of lung SBRT. Female sex, synchronous SBRT, prior G2+ RILT, and higher composite lung V20 may be risk factors for G2+ RILT. (c) 2023 The Authors. Published by Elsevier Inc. on behalf of American Society for Radiation Oncology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

5094 Background: The impact of prostate cancer treatments on sexual health outcomes in sexual minority men (SMM), especially in those who engage in receptive anal intercourse (RAI), remains an underrepresented area of scientific investigation. Additionally, limited data exist on differences between treatment-related sexual dysfunction in SMM and heterosexual men (HET). Methods: We conducted an exploratory retrospective analysis of a cohort of sexually active cancer survivors with intact prostates who were seen at least 6 months post-radiotherapy (RT), completed androgen deprivation therapy (ADT), and presented for follow-up between 6/2022 and 8/2023. Patients self-reported sexual orientation, gender identity, sex at birth, sexual behaviors, and PROMIS SexFS scores for orgasm ability, orgasm pleasure, sexual satisfaction, and anal discomfort domains. Average PROMIS scores were compared to the U.S. general population of adult men normative standard scores and between subgroups with mean differences [MD] and t-tests. We considered MD > 3 points to be clinically meaningful. SHIM scores were dichotomized to erectile dysfunction (<16) and function (>17), and analyzed with logistic regression at baseline, 1-, and 2-years post-RT. Results: Of eligible HET and SMM, 39% HET (n=57/145) and 68% SMM (n=21/31) were sexually active with a partner (p=0.005); including 15 (71%) SMM who reported engaging in RAI. Overall, 8% were treated with brachytherapy, 46% external beam radiotherapy, and 46% both; 14% of patients received ADT. Median age was 66 years (interquartile range [IQR]: 61, 71), and median time to survey was 1.3 years (IQR: 0.9, 3.3). The cohort reported worse orgasm function (MD: 3.3, [95% CI: 0.9, 4.7], p<0.01), orgasm pleasure (MD: 7.2, [95% CI: 5.3, 9.1], p<0.001), and satisfaction (MD: 3.4, [95% CI: 1.9, 4.9], p<0.001) compared to norms. Very few demographic or outcome differences were observed between SMM and HET. SMM were more likely to be single (71%) than HET (33%, p<0.005). No differences in erectile function were observed between HET and SMM engaging in insertive intercourse. However, sexually active SMM engaging in RAI reported clinically meaningful differences in orgasm ability (MD: 3.5, [95% CI: -2.9, 9.9], p=0.1), orgasm pleasure (MD: 6.3, [95% CI: 5.2, 9.2], p=0.05), and anal discomfort (MD: 9.0, [95% CI: -0.9, 18.9], p=0.06) but not in satisfaction compared to norms. No clinically meaningful differences were observed by radiation modality. Conclusions: Prostate RT impacts sexual function in HET and SMM. However, the distinct health concerns of SMM and the unique functional anatomy involved in RAI underscore the need for prostate cancer clinicians and researchers to include RAI in sexual outcomes, collect data specific to SMM, and develop targeted interventions for this historically neglected cohort.

The COVID-19 pandemic forced educators and students to transition to online instruction. This change brought the importance of user interfaces into stark relief for engineering lab classes, compelling educators to consider how the design of online courses and virtual laboratory experiences either served or worked against student learning. In summer 2020, we began educational and user experience (UX) research with the online laboratory experiences in an electrical engineering lab classroom at the [anonymized] College of Engineering. The NSF-funded project work draws on ready-to-use remote labs for electronics applied to several courses. It seeks to explore the faculty and student perspective on online experimentation in engineering curricula. However, the UX thrust of the project rounds out a holistic view of the online learning ecosystem and might specifically uncover barriers or factors of success related to the implementation of online labs. This project highlighted the importance of UX design in delivering science curriculum via virtual laboratory exercises with the specific conclusion that deficits in perspicuity in the UX create an obstacle to learning for engineering students.

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.Studies addressing outcomes after pediatric radiation therapy are particularly challenging because: (a) survivors may live for decades after treatment, and the latency time to toxicity can be very long; (b) children's maturation can be affected by radiation, depending on the developmental status of the organs involved at time of treatment; and (c) treatment regimens frequently involve chemotherapies, possibly modifying and adding to the toxicity of radiation.Here we discuss: basic reporting strategies to account for the actuarial nature of the complications; the reporting of modeling of abnormal development; and the need for standardized, comprehensively reported data sets and multivariate models (ie, accounting for the simultaneous effects of radiation dose, age, developmental status at time of treatment, and chemotherapy dose). We encourage the use of tools that facilitate comprehensive reporting, for example, electronic supplements for journal articles.Finally, we stress the need for clinicians to be able to trust artificial intelligence models of outcome of radiation therapy, which requires transparency, rigor, reproducibility, and comprehensive reporting. Adopting the reporting methods discussed here and in the individual PENTEC articles will increase the clinical and scientific usefulness of individual reports and associated pooled analyses.

PURPOSE:We hypothesized that an in-house developed system using megavoltage and kilovoltage image guidance (MKIG) to ensure correct prostate positioning during stereotactic body radiation therapy (SBRT) could potentially avoid unwanted doses to nontarget tissues, leading to reduced toxicities. METHODS AND MATERIALS:We built a 3-dimensional MKIG platform that accurately tracks prostate implanted fiducials in real time and clinically translated the system to replace a commercial approach, intrafraction motion review (IMR), which only tracks fiducials in the 2-dimensional kilovoltage views. From 2017 to 2019, 150 patients with prostate cancer were treated with SBRT and monitored using MKIG. The motion trace of the fiducials alerts therapists to interrupt and reposition the prostate when displacement exceeds a 1.5 mm threshold. A comparison cohort of 121 patients was treated with the same dose regimen and treatment technique but managed by IMR. Statistics of intrafractional patient shifts and delivery time were collected to evaluate the workflow efficacy. The incidence of grade ≥2 urinary toxicities was analyzed to assess clinical complications. The median follow-up time was 3.7 years (0.2-8.2 years). RESULTS:MKIG treatments had more treatment shifts (1.09 vs 0.28) and a longer average delivery time per fraction (579 ± 205 seconds vs 357 ± 117 seconds) than IMR treatments. Three-quarters (75%) of shifts resulting from MKIG were ≤3 mm, versus 51% in IMR, indicating that MKIG detected and corrected smaller deviations. The incidence of grade ≥2 urinary toxicity was lower in the MKIG than the IMR cohort: 10.7% versus 19.8% (P = .047). On multivariate analysis of late urinary toxicity, only high (>7) preradiation therapy international prostate symptom score (P < .043) and the use of MKIG were selected (P < .029). CONCLUSIONS:Automated and quantitative MKIG introduced minimal workflow impact and was superior to IMR in localizing the prostate during SBRT, which correlated with a clinically significant reduction in late urinary toxicity. Further clinical testing using randomized trials will be required to validate the impact on outcomes.

Background and Purpose: Safe reirradiation relies on assessment of cumulative doses to organs at risk (OARs) across multiple treatments. Different clinical pathways can result in inconsistent estimates. Here, we quantified the consistency of cumulative dose to OARs across multi -centre clinical pathways. Material and Methods: We provided DICOM planning CT, structures and doses for two reirradiation cases: head & neck (HN) and lung. Participants followed their standard pathway to assess the cumulative physical and EQD2 doses (with provided alpha/beta values), and submitted DVH metrics and a description of their pathways. Participants could also submit physical dose distributions from Course 1 mapped onto the CT of Course 2 using their best available tools. To assess isolated impact of image registrations, a single observer accumulated each submitted spatially mapped physical dose for every participating centre. Results: Cumulative dose assessment was performed by 24 participants. Pathways included rigid (n = 15), or deformable (n = 5) image registration -based 3D dose summation, visual inspection of isodose line contours (n = 1), or summation of dose metrics extracted from each course (n = 3). Largest variations were observed in nearmaximum cumulative doses (25.4 - 41.8 Gy for HN, 2.4 - 33.8 Gy for lung OARs), with lower variations in volume/dose metrics to large organs. A standardised process involving spatial mapping of the first course dose to the second course CT followed by summation improved consistency for most near -maximum dose metrics in both cases. Conclusion: Large variations highlight the uncertainty in reporting cumulative doses in reirradiation scenarios, with implications for outcome analysis and understanding of published doses. Using a standardised workflow potentially including spatially mapped doses improves consistency in determination of accumulated dose in reirradiation scenarios.

At its very core, radiation oncology involves a trade-off between the benefits and risks of exposing tumors and normal tissue to relatively high doses of ionizing radiation. This trade-off is particularly critical in childhood cancer survivors (CCS), in whom both benefits and risks can be hugely consequential due to the long life expectancy if the primary cancer is controlled. Estimating the normal tissue-related risks of a specific radiation therapy plan in an individual patient relies on predictive mathematical modeling of empirical data on adverse events. The Pediatric Normal-Tissue Effects in the Clinic (PENTEC) collaborative network was formed to summarize and, when possible, to synthesize dose-volume-response relationships for a range of adverse events incident in CCS based on the literature. Normal-tissue clinical radiation biology in children is particularly challenging for many reasons: (1) Childhood malignancies are relatively uncommon-constituting approximately 1% of new incident cancers in the United States-and biologically heterogeneous, leading to many small series in the literature and large variability within and between series. This creates challenges in synthesizing data across series. (2) CCS are at an elevated risk for a range of adverse health events that are not specific to radiation therapy. Thus, excess relative or absolute risk compared with a reference population becomes the appropriate metric. (3) Various study designs and quantities to express risk are found in the literature, and these are summarized. (4) Adverse effects in CCS often occur 30, 50, or more years after therapy. This limits the information content of series with even very extended follow-up, and lifetime risk estimates are typically extrapolations that become dependent on the mathematical model used. (5) The long latent period means that retrospective dosimetry is required, as individual computed tomography-based radiation therapy plans gradually became available after 1980. (6) Many individual patient-level factors affect outcomes, including age at exposure, attained age, lifestyle exposures, health behaviors, other treatment modalities, dose, fractionation, and dose distribution. (7) Prospective databases with individual patient-level data and radiation dosimetry are being built and will facilitate advances in dose-volume-response modeling. We discuss these challenges and attempts to overcome them in the setting of PENTEC.

PurposeReirradiation 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 MaterialsA 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. Seventeen studies representing 449 patients who reported brain and brain stem necrosis after reirradiation contained sufficient data for analysis. While all 17 studies described techniques and doses used for reirradiation, they lacked essential details on clinically significant dose-volume metrics necessary for dose-response modeling on late effects. We, therefore, estimated incidences of necrosis with an exact 95% CI and qualitatively described data. Results from multiple studies were pooled by taking the weighted average of the reported crude rates from individual studies.ResultsTreated cancers included ependymoma (n = 279 patients; 7 studies), medulloblastoma (n = 98 patients; 6 studies), any CNS tumors (n = 62 patients; 3 studies), and supratentorial high-grade gliomas (n = 10 patients; 1 study). The median interval between initial and reirradiation was 2.3 years (range, 1.2-4.75 years). The median cumulative prescription dose in equivalent dose in 2-Gy fractions (EQD22; assuming α/β value = 2 Gy) was 103.8 Gy (range, 55.8-141.3 Gy). Among 449 reirradiated children/AYA, 22 (4.9%; 95% CI, 3.1%-7.3%) developed brain necrosis and 14 (3.1%; 95% CI, 1.7%-5.2%) developed brain stem necrosis with a weighted median follow-up of 1.6 years (range, 0.5-7.4 years). The median cumulative prescription EQD22 was 111.4 Gy (range, 55.8-141.3 Gy) for development of any necrosis, 107.7 Gy (range, 55.8-141.3 Gy) for brain necrosis, and 112.1 Gy (range, 100.2-117 Gy) for brain stem necrosis. The median latent period between reirradiation and the development of necrosis was 5.7 months (range, 4.3-24 months). Though there were more events among children/AYA undergoing hypofractionated versus conventionally fractionated reirradiation, the differences were not statistically significant (P = .46).ConclusionsExisting reports suggest that in children/AYA with recurrent brain tumors, reirradiation with a total EQD22 of about 112 Gy is associated with an approximate 5% to 7% incidence of brain/brain stem necrosis after a median follow-up of 1.6 years (with the initial course of radiation therapy being given with conventional prescription doses of ≤2 Gy per fraction and the second course with variable fractionations). We recommend a uniform approach for reporting dosimetric endpoints to derive robust predictive models of late toxicities following reirradiation.