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Purpose Quality assurance (QA) practices improve the quality level of oncology trials by ensuring that the protocol is followed and the results are valid and reproducible. This study investigated the utilization of QA among randomized controlled trials that involve radiotherapy (RT). Methods and Materials We searched ClinicalTrials.gov in February 2020 for all phase III oncology randomized clinical trials (RCTs). These trials were screened for RT-specific RCTs that had published primary trial results. Information regarding QA in each trial was collected from the study publications and trial protocol if available. Two individuals independently performed trial screening and data collection. Pearson’s Chi-square tests analyses were used to assess factors that were associated with QA inclusion in RT trials. Results Forty-two RCTs with RT as the primary intervention or as a mandatory component of the protocol were analyzed; the earliest was started in 1994 and one trial was still active though not recruiting. Twenty-nine (69%) trials mandated RT quality assurance (RTQA) practices as part of the trial protocol, with 19 (45%) trials requiring institutional credentialing. Twenty-one (50%) trials published protocol deviation outcomes. Clinical trials involving advanced radiation techniques (IMRT, VMAT, SRS, SBRT) did not include more RTQA than trials without these advanced techniques (73% vs. 65%, p=0.55). Trials that reported protocol deviation outcomes were associated with mandating RTQA in their protocols as compared to trials that did not report these outcomes (100% vs. 38%, p Conclusions There is a lack of RTQA utilization and transparency in RT clinical trials. It is imperative for RT trials to include increased QA for safe, consistent, and high-quality RT planning and delivery.

Young patients, including pediatric, adolescent, and young adult (YA) patients, are most likely to benefit from the reduced integral dose of proton beam radiation therapy (PBT) resulting in fewer late toxicities and secondary malignancies. This study sought to examine insurance approval and appeal outcomes for PBT among YA patients compared with pediatric patients at a large-volume proton therapy center.We performed a cross-sectional cohort study of 284 consecutive patients aged 0 to 39 years for whom PBT was recommended in 2018 through 2019. Pediatric patients were defined as aged 0 to 18 years and YA patients 19 to 39 years. Rates of approval, denials, and decision timelines were calculated. Tumor type and location were also evaluated as factors that may influence insurance decisions.A total of 207 patients (73%) were approved for PBT at initial request. YA patients (n = 68/143, 48%) were significantly less likely to receive initial approval compared with pediatric patients (n = 139/141; 99%) (P.001). Even after 47% (n = 35 of 75) of the PBT denials for YA patients were overturned, YAs had a significantly lower final PBT approval (72% vs pediatric 99%; P.001). The median wait time was also significantly longer for YA patients (median, 8 days; interquartile range [IQR] 3-17 vs median, 2 days; IQR, 0-6; P.001). In those patients requiring an appeal, the median wait time was 16 days (IQR, 9-25).Given the decades of survivorship of YA patients, PBT is an important tool to reduce late toxicities and secondary malignancies. Compared with pediatric patients, YA patients are significantly less likely to receive insurance approval for PBT. Insurance denials and subsequent appeal requests result in significant delays for YA patients. Insurers need to re-examine their policies to include expedited decisions and appeals and removal of arbitrary age cutoffs so that YA patients can gain easier access to PBT. Furthermore, consensus guidelines encouraging greater PBT access for YA may be warranted from both medical societies and/or AYA experts.

Background To determine if proton radiotherapy (PT), compared to intensity-modulated radiotherapy (IMRT), delayed time to cognitive failure in patients with newly diagnosed glioblastoma (GBM). Methods Eligible patients were randomized unblinded to PT vs IMRT. The primary endpoint was time to cognitive failure. Secondary endpoints included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported outcomes (PROs). Results A total of 90 patients were enrolled and 67 were evaluable with median follow-up of 48.7 months (range 7.1-66.7). There was no significant difference in time to cognitive failure between treatment arms (HR, 0.88; 95% CI, 0.45-1.75; P = .74). PT was associated with a lower rate of fatigue (24% vs 58%, P = .05), but otherwise, there were no significant differences in PROs at 6 months. There was no difference in PFS (HR, 0.74; 95% CI, 0.44-1.23; P = .24) or OS (HR, 0.86; 95% CI, 0.49-1.50; P = .60). However, PT significantly reduced the radiation dose for nearly all structures analyzed. The average number of grade 2 or higher toxicities was significantly higher in patients who received IMRT (mean 1.15, range 0-6) compared to PT (mean 0.35, range 0-3; P = .02). Conclusions In this signal-seeking phase II trial, PT was not associated with a delay in time to cognitive failure but did reduce toxicity and patient-reported fatigue. Larger randomized trials are needed to determine the potential of PT such as dose escalation for GBM and cognitive preservation in patients with lower-grade gliomas with a longer survival time.

Purpose This study aimed to report on the safety, feasibility, and workflow of using magnetic resonance imaging (MRI) simulation, while immobilized in the treatment position, for radiation therapy treatment planning in the pediatric population. Methods and Materials Between May and December 2017, 10 pediatric patients completed both MRI and computed tomography imaging simulation in treatment immobilization for radiation therapy planning for central nervous system disease. We report our initial institutional experience and workflow of the use of MRI simulation in immobilization for treatment planning in this population. Results Ten pediatric patients successfully underwent MRI and computed tomography imaging simulation for CNS disease. Two patients required anesthesia for sedation during the simulations. From our initial experience, MRI simulation was tolerated by all 10 pediatric patients without any safety or clinical issues, including those who required anesthesia. Conclusions Our initial experience supports the use of MRI simulation for radiation treatment planning in the pediatric population, with and without anesthetic sedation, as a safe and feasible image-guidance tool. This is particularly useful in the treatment of pediatric patients because MRI simulation enables superior, soft-tissue, anatomic imaging for a more robust delineation of organs at risk and target volumes without increasing radiation exposure.

Purpose/objective(s) Chordomas are rare tumors of notochordal origin affecting the skull base, spine, and sacrum. Given their high propensity for local recurrence and chemo/radioresistant biology, current treatment paradigms involve maximally safe en-bloc resection with or without adjuvant radiation therapy (RT). SSRS describes a modern approach to dose escalated RT, most commonly used for spine metastases. We analyzed our large single-institution database to test the hypothesis that SSRS provides comparable oncologic and safety outcomes relative to historical controls. Materials/methods We identified 21 patients with mobile spine or sacral chordoma (25 lesions) treated with SSRS at our institution from 2006 to 2020. We reviewed records to obtain patient, disease, and treatment characteristics, as well as outcome data including survival, local control, and toxicity attributable to SSRS. We performed a Kaplan-Meier analysis to estimate overall survival and local control rates, and a Cox proportional hazard model was used for univariate and multivariate analysis. We also performed a logistic regression to examine risk factors for insufficiency fractures. Significance was defined at a P Results Patients were treated with IMRT in 1,3, or 5 fractions with a simultaneous integrated boost. The median BED2 was 312 Gy (24 Gy/1 fraction to the GTV, 16 Gy to CTV) (Range 120-312 Gy). 44% of lesions were treated in the salvage setting, and 36% were treatments for metastases. All patients had gross disease at the time of SSRS. With median follow-up of 30 months, overall survival (OS) was 95.0%, 89.1%, 48.2% and local control (LC) was 91.5%, 86.9%, and 55.3% at 1, 2, and 5 years respectively. Covariates significantly associated with OS included: performance status, prescribed BED, mobile spine location, non-metastatic site treated, disease limited to 1 site, and GTV Dmin BED2 > 119.28), and the multivariate analysis did not converge. Covariates significantly associated with LC on univariate analysis included: conventional histology, and prescribed BED, while chondroid histology was associated with decreased LC. Only prescribed BED was significant on multivariate analysis. Seven patients were treated with definitive SSRS to their primary site, and there was 1 death (not attributable to RT) and 1 local failure in this group. No radiation myelopathy events were identified. Six patients (29%) required stabilization for sacral or spinal insufficiency after SSRS (median 13 months). No features were identified that significantly predicted for fracture. Conclusion To the best of our knowledge, this series represents over a quarter of all reported spine and sacrum chordoma cases treated with stereotactic radiation in the literature. Our data are comparable to published population-based and single-institution case series, particularly given the prevalence of salvage and metastatic cases in this cohort, and they support the use of SSRS throughout the disease course of spine and sacral chordoma. Author disclosure S. Maroongroge: None. D. Boyce-Fappiano: None. K. Diao: None. B. Amini: None. A.P. Conley: None. J. Li: Research Grant; BMS, Medtronic. Honoraria; Monteris. Travel Expenses; Elekta. D.N. Yeboa: Research Grant; Brockman Foundation, MD Anderson Shirley Stein Award, MD Anderson Cancer Center. member for reviewing abstracts; ASTRO.M. McAleer: Honoraria; PREX S. p. A., AOSpine, Osler Institute. Speaker's Bureau; Osler Institute. Travel Expenses; Osler Institute. C. Tatsui: None. L.D. Rhines: None. A.J. Ghia: None.

Purpose/Objective(s) Brainstem toxicity after radiation is a devastating complication and a particular concern with proton radiation (RT), given the biological differences and range uncertainties at the distal edge of proton beam. Data from St. Jude's found a 3.7% risk of brainstem necrosis after photon-based RT, while the incidence with protons ranges from 0.7% - 31% across studies. We investigated the incidence and clinical correlates of brainstem injury in pediatric brain tumors treated with proton therapy. Materials/Methods All patients 30 Gy and/or Dmax > 50.4 Gy were included. We excluded patients with primary brainstem tumors. Symptomatic brainstem injury (SBI) was defined as any new or progressive cranial neuropathy, ataxia, dysmetria and/or motor weakness with corresponding radiographic abnormality within the brainstem and was graded per the NCI Common Terminology Criteria for Adverse Events v5.0 (Grade 2: moderate symptoms, corticosteroids indicated; Grade 3: severe symptoms, medical intervention indicated; Grade 4: life-threatening; urgent intervention; and Grade 5: death). Results A total of 595 patients were reviewed and 362 (medulloblastoma = 209, ependymoma = 86, ATRT = 43, pineoblastoma = 9, others = 15) met our inclusion criteria. Median age at RT was 5 years (range 0.7 – 17.9 years) and median prescribed RT dose was 54 CGyE (range 39.6 – 59.4 CGyE). Median follow up was 40 months (range 1 – 152). Ten patients (2.7%) developed SBI, at a median of 4 months after RT (range 1-6). Grades 2,3,4 and 5 brainstem injuries were seen in 3, 4, 2 and 1 patient respectively. Mean brainstem Dmax in SBI and non-SBI patients was 55.9 Gy and 54.8 Gy (P = 0.30), while the mean Dmean was 43.3 Gy and 43.2 Gy (P = 0.48) respectively. Most common symptoms of SBI were ataxia, slurred speech, 6th cranial nerve palsy and bulbar palsy. All SBI patients required steroids for 1-5 months, while grade 3-5 injuries were also treated with bevacizumab and/or hyperbaric oxygen therapy. Asymptomatic imaging changes within brainstem were seen in 47 patients (13%) at a median of 4 months after RT, most common findings being increased T2 flair, focal enhancement and encephalomalacia. In 2014, our institution started using strict brainstem dose constraints (Dmax ≤ 57 Gy, Dmean ≤ 52.4 Gy and V54 ≤ 10%). The incidence of SBI has decreased from 4.2% (2007-2013) to 0.7% (2014-2019) (P = 0.047) while asymptomatic imaging changes remain similar (11.6% vs 15.1%, P = 0.33). Patients with SBI had a higher V45, V50-52 and D15 -D50; while the Dmax, Dmean, V53-60 and D1- D10 were similar. Conclusion Our results suggest that there is a low risk of SBI after proton therapy for pediatric brain tumors. A lower incidence of SBI was seen after the use of strict brainstem dose constraints. Volumetric doses to brainstem may play a significant role in determining the risk of SBI and developing a dose response nomogram is warranted.

PURPOSE/OBJECTIVE(S) Craniospinal irradiation (CSI) with photons is associated with significant toxicities. The use of electrons for spinal fields is hypothesized to spare anterior structures but its long-term effects remain poorly characterized. We studied late effects of CSI using electrons for spinal radiotherapy (RT). MATERIALS/METHODS Records of 84 consecutive patients treated with CSI using electrons for the spine at a single institution from 1983-2014 were reviewed. Median age at RT was 5 (range, 1-14) years with 60% male. Most common histologies were medulloblastoma/PNET (59%) and ependymoma (8%). Most commonly used electron energies were 16 (44%) and 20 (25%) MeV (range, 12-21). Median prescribed dose to the entire spine was 30 (range 6-45) Gy. A spinal boost was used in 14%. A subset of 47 (56%) patients was analyzed for late effects with the following inclusion criteria: 1) age between 2 and 14 years at time of CSI, and 2) clinical and radiographic follow-up for ≥ 5 years. Height z-scores adjusted for age before and after CSI were assessed using CDC stature-for-age charts and compared with a t-test. A Cobb angle of > 10° was used to identify scoliosis. RESULTS At a median follow-up of 18 (range, 0-37) years, the median survival was 22 (95% confidence interval [CI], 12-28) years with 50 patients (60%) alive at last follow up. On subset analysis for late effects, 18 (38%) patients developed hypothyroidism and 4 (9%) developed secondary malignancies possibly attributable to spine RT (3 papillary thyroid cancer, 1 renal cell carcinoma) at a median 26 (range, 10-33) years after RT. Chronic pulmonary issues were seen in 2 patients (restrictive lung disease, recurrent pneumonia) and 1 patient developed esophageal strictures and periaortic hemorrhage. No patients developed myelopathy or cardiotoxicity. Median height z-score prior to treatment was -0.3 (37th percentile; interquartile range [IQR], -1.0 to +0.1) and at last follow up after RT was -2.2 (1st percentile; IQR, -3.1 to -1.5; P < 0.001). Of 42 patients with spinal curvature assessments, 14 (33%) had scoliosis with median Cobb angle 16° (IQR, 14-18°). CONCLUSION Long-term follow-up of children treated with CSI using electron spinal fields showed frequent musculoskeletal toxicity, predominantly decreased height. Scoliosis and hypothyroidism were seen in at least a third of long-term survivors. Esophageal, pulmonary, cardiac and spinal cord toxicities were infrequent.