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Background: Simultaneous involvement of multiple distinct brain regions occurs in 2-5% of all high-grade gliomas (HGG) and is associated with poor prognosis. Whereas radiotherapy (RT) is an important and well-established treatment for high-grade glioma, the role of dose-escalated radiotherapy has yet to be established. In this case series, we report upon the dosimetry, adverse effects, and response in patients with multiple un-methylated high-grade gliomas receiving dose-escalated radiation. Materials and methods: We reviewed charts of patients with multifocal high grade glioma treated at our institution since January 2022. All patients had stereotactic biopsies after an magnetic resonance imaging (MRI) contrast-enhanced with T1, T2, FLAIR sequences and were discussed in a multidisciplinary oncology team. MGMT-positive patients received either TMZ alone or RT with TMZ and were excluded from this analysis. Un-methylated patients received dose-escalated RT without temezolamide (TMZ). Following computed tomography (CT) and MR simulation, the gros tumor volume (GTV) was delineated and prescribed 52.5 Gy in 15 fractions within the standard 40.05 Gy planning treatment volume (PTV). Treatment planning was volumetric modulated arc therapy. Results: A total of 20 patients with multiple un-methylated MGMT glioblastoma multiforme were treated with dose-escalated radiation therapy between January 2022 and June 2023. All patients completed dose escalated radiotherapy without acute adverse effects. Progression-free survival at six months was 85%, as defined by the RANO criteria. Conclusion: In this case series, we showed that un-methylated multiple high-grade glioma could be safely treated with dose escalation. Results of progression-free survival should be validated in a larger prospective clinical trial. [ABSTRACT FROM AUTHOR]

Five fraction salvage stereotactic body radiation therapy (SBRT) is a Delphi consensus recommendation for prostate re-irradiation, yet remains debatable and underutilized, and is associated with higher risk of treatment-related adverse events compared to primary radiotherapy. We hypothesized that intensification of hypo-fractionation delivering 2 fractions of 9 GY would be advantageous and here report the feasibility, toxicity, and preliminary outcomes of 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) directed salvage focal re-irradiation with this regimen. From July 2022 to November 2023, 17 Men with isolated prostate cancer recurrence after definitive radiation were treated at single institution. All patients underwent 68Ga-PSMA PET/CT following biochemical recurrence by the phoenix criteria or a repeated PSA increase. Confirmation of recurrence was performed by prostate biopsy and multiparametric MRI in 53% and 35% of patients, respectively. Focal SBRT of 18 Gy in two fractions was delivered to the PSMA-avid disease and a 3-5mm margin in the prostate on alternate days with image guidance by fiducial markers. Placement of hydrogel spacer (29%) or endorectal balloon (71%) was mandated. Androgen deprivation therapy was given concurrently in 88% of patients for a median duration of six months (range = 4-21). Toxicity was assessed according to Common Terminology Criteria for Adverse Events version 5. Median follow-up was 11.9 months (range = 3-18) with a median time between primary radiation treatment and salvage SBRT of 4.3 years (range = 0.6- 15.6). Median age was 73.1 (range = 66-89) and Prostate-specific antigen (PSA) level at reirradiation was 1.87 ng/ml (range = 0.02-7.1). At the end of follow up only one patient had a biochemical recurrence, which was confirmed by 68Ga-PSMA PET/CT. No patient developed acute or late gastrointestinal toxicity, and four patients (23.5%) did not have any adverse events. Rates of acute genitourinary (GU) toxicity grade 1 and 2 were 41.2% and 11.8%, respectively. Late grade 1 and 2 GU toxicity occurred in 41% and 35%, with cystitis as the leading toxicity followed by urinary incontinence. No grade 3 or 4 toxicities were reported. With a short follow-up, PSMA-directed salvage focal reirradiation to the prostate using SBRT of 18 Gy in two fractions is feasible and has acceptable toxicity. No gastrointestinal toxicity was reported, as well as no high-grade toxicity of any type, with very favorable short term biochemical control in a selected cohort of patients. [ABSTRACT FROM AUTHOR]

Purpose: The aim was to determine the efficacy, safety, and tolerability of weekly ultra hypofractionated radiation therapy for older unfit patients with invasive bladder cancer., Methods: We retrospectively analyzed a cohort of patients with muscle invasive bladder cancer deemed unfit for chemoradiation therapy and thus treated with 6 weekly doses of 6 Gy using intensity modulated radiotherapy. Charlson comorbidity was calculated retrospectively. Cystoscopy and computed tomography were used to evaluate local control and toxicity using the common terminology criteria. Survival outcomes were estimated using the Kaplan-Meier method., Results: Twenty-two patients with a median age of 84 (range: 70 to 96) years were included. The median comorbidity index was 6±1.5 SD. Nineteen (90%) patients received the full 36 Gy dose. Median follow-up was 10±7 months (range: 6 to 27 mo). Local control in the bladder was achieved in 16 of 19 evaluable patients (84%). One-year overall survival was 62.5%, 1 patient had a retroperitoneal nodal recurrence and 3 patients developed distant metastasis. Grade 3 genitourinary and gastrointestinal toxicity was observed in 4 (18%) and 1 (4.5%) patients, respectively., Conclusion: Weekly ultra hypofractionated intensity modulated radiotherapy with image guidance and bladder training is an effective, safe, and well-tolerated regimen for older patients with invasive bladder cancer unfit for radical treatment., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Advances in imaging, biomaterials and precision radiotherapy provide new opportunities to salvage locally recurrent prostate cancer (PC). This study evaluates the efficacy and safety of re-irradiation using stereotactic body radiation therapy (SBRT). We hypothesized that patients with castrate-resistant PC (CRPC) would benefit less from local salvage., Methods: A prospective clinical database was reviewed to extract 30 consecutive patients treated with prostate re-irradiation. Gallium prostate specific membrane antigen (PSMA) ligand positron emission tomography was performed following prostate-specific antigen failure in all patients and biopsy was obtained in 18 patients (60%). Re-irradiation was either focal (n = 13) or whole-gland (n = 17). Endo-rectal balloons were used in twenty-two patients and hydrogel spacers in eight patients. The median prescription dose was 5 fractions of 6.5 (range: 6-8) Gray (Gy)., Results: Median follow-up was 28 months. Failure occurred in 10 (out of 11) CRPC patients versus 6 (out of 19) castrate-sensitive patients (91% vs. 32%, p = 0.008) after a median of 13 and 23 months, respectively. Metastases occurred in 64% (n = 7) of CRPC patients versus 16% (n = 3) of castrate-sensitive patients (p = 0.007). Two patients experienced local in-field recurrence, thus local control was 93%. The 2 and 3-year recurrence-free survival were 84% and 79% for castrate-sensitive patients versus 18% and 9% for CRPC patients (p < 0.001), and 3-year metastasis-free survival was 90% versus 27% (p < 0.01) for castrate-sensitive and CRPC patients, respectively. Acute grade II and III genitourinary (GU) toxicity occurred in 27% and 3%, and late GU toxicity in 30% and 3%, respectively. No ≥ grade II acute gastrointestinal (GI) toxicity occurred, and only one patient (3%) developed late grade II toxicity., Conclusions: Early delivery of salvage SBRT for local recurrence is associated with excellent 3-year disease control and acceptable toxicity in the castrate-sensitive phenotype. PSMA imaging for detection of local recurrence and the use of precision radiotherapy with rectal protective devices should be further investigated as a novel salvage strategy for radio-recurrent PC.

Purpose: To present the radiation therapy quality assurance results from a prospective multicenter phase 2 randomized trial of short versus protracted urethra-sparing stereotactic body radiation therapy (SBRT) for localized prostate cancer., Methods and Materials: Between 2012 and 2015, 165 patients with prostate cancer from 9 centers were randomized and treated with SBRT delivered either every other day (arm A, n = 82) or once a week (arm B, n = 83); 36.25 Gy in 5 fractions were prescribed to the prostate with (n = 92) or without (n = 73) inclusion of the seminal vesicles (SV), and the urethra planning-risk volume received 32.5 Gy. Patients were treated either with volumetric modulated arc therapy (VMAT; n = 112) or with intensity modulated radiation therapy (IMRT; n = 53). Deviations from protocol dose constraints, planning target volume (PTV) homogeneity index, PTV Dice similarity coefficient, and number of monitor units for each treatment plan were retrospectively analyzed. Dosimetric results of VMAT versus IMRT and treatment plans with versus without inclusion of SV were compared., Results: At least 1 major protocol deviation occurred in 51 patients (31%), whereas none was observed in 41. Protocol violations were more frequent in the IMRT group (P < .001). Furthermore, the use of VMAT yielded better dosimetric results than IMRT for urethra planning-risk volume D 98% (31.1 vs 30.8 Gy, P < .0001), PTV D 2% (37.9 vs 38.7 Gy, P < .0001), homogeneity index (0.09 vs 0.10, P < .0001), Dice similarity coefficient (0.83 vs 0.80, P < .0001), and bladder wall V 50% (24.5% vs 33.5%, P = .0001). To achieve its goals volumetric modulated arc therapy required fewer monitor units than IMRT (2275 vs 3378, P <.0001). The inclusion of SV in the PTV negatively affected the rectal wall V 90% (9.1% vs 10.4%, P = .0003) and V 80% (13.2% vs 15.7%, P = .0003)., Conclusions: Protocol deviations with potential impact on tumor control or toxicity occurred in 31% of patients in this prospective clinical trial. Protocol deviations were more frequent with IMRT. Prospective radiation therapy quality assurance protocols should be strongly recommended for SBRT trials to minimize potential protocol deviations., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Intensity-modulated radiotherapy (IMRT) has better normal-tissue sparing compared with 3-dimensional conformal radiation (3DCRT). We sought to assess the impact of radiation technique on pathological and clinical outcomes in locally advanced non-small cell lung cancer (LANSCLC) treated with a trimodality strategy., Methods: Retrospective review of LANSCLC patients treated from August 2012 to August 2018 at Sheba Medical Center, Israel. The trimodality strategy consisted of concomitant chemoradiation to 60 Gray (Gy) followed by completion surgery. The planning target volume (PTV) was defined by co-registered PET/CT. Here we compare the pathological regression, surgical margin status, local control rates (LC), disease free (DFS) and overall survival (OS) between 3DCRT and IMRT., Results: Our cohort consisted of 74 patients with mean age 62.9 years, male in 51/74 (69%), adenocarcinoma in 46/74 (62.1%), stage 3 in 59/74 (79.7%) and chemotherapy in 72/74 (97.3%). Radiation mean dose: 59.2 Gy (SD ± 3.8). Radiation technique : 3DCRT in 51/74 (68.9%), IMRT in 23/74 (31%). Other variables were similar between groups.Major pathological response (including pathological complete response or less than 10% residual tumor cells) was similar: 32/51 (62.7%) in 3DCRT and 15/23 (65.2%) in IMRT, p=0.83. Pathological complete response (pCR) rates were similar: 17/51 (33.3%) in 3DCRT and 8/23 (34.8%) in IMRT, p=0.9. Surgical margins were negative in 46/51 (90.1%) in 3DCRT vs. 17/19 (89.4%) in IMRT (p=1.0).The 2-year LC rates were 81.6% (95% CI 69-89.4%); DFS 58.3% (95% CI 45.5-69%) and 3-year OS 70% (95% CI57-80%). Comparing radiation techniques, there were no significant differences in LC (p=0.94), DFS (p=0.33) and OS (p=0.72)., Conclusion: When used to treat LANSCLC in the neoadjuvant setting, both IMRT and 3DCRT produce comparable pathological and clinical outcomes., Advances in Knowledge: This study validates the real-world effectiveness of IMRT compared to 3DCRT.

Background: This is a dosimetric comparative study intended to establish appropriate low-to-intermediate dose-constraints for the rectal wall (R wall ) in the context of a randomized phase-II trial on urethra-sparing stereotactic body radiotherapy (SBRT) for prostate cancer. The effect of plan optimization on low-to-intermediate R wall dose and the potential benefit of an endorectal balloon (ERB) are investigated., Methods: Ten prostate cancer patients, simulated with and without an ERB, were planned to receive 36.25Gy (7.25Gyx5) to the planning treatment volume (PTV) and 32.5Gy to the urethral planning risk volume (uPRV). Reference plans with and without the ERB, optimized with respect to PTV and uPRV coverage objectives and the organs at risk dose constraints, were further optimized using a standardized stepwise approach to push down dose constraints to the R wall in the low to intermediate range in five sequential steps to obtain paired plans with and without ERB (Vm 1 to Vm 5 ). Homogeneity index for the PTV and the uPRV, and the Dice similarity coefficient (DSC) for the PTV were analyzed. Dosimetric parameters for R wall including the median dose and the dose received by 10 to 60% of the R wall , bladder wall (B wall ) and femoral heads (F Heads ) were compared. The monitor units (MU) per plan were recorded., Results: Vm 4 reduced by half D 30% , D 40% , D 50%, and D med for R wall and decreased by a third D 60% while HI PTV , HI uPRV and DSC remained stable with and without ERB compared to Vm ref . HI PTV worsened at Vm 5 both with and without ERB. No statistical differences were observed between paired plans on R wall , B wall except a higher D 2% for F heads with and without an ERB., Conclusions: Further optimization to the R wall in the context of urethra sparing prostate SBRT is feasible without compromising the dose homogeneity to the target. Independent of the use or not of an ERB, low-to-intermediate doses to the R wall can be significantly reduced using a four-step sequential optimization approach.

OBJECTIVE Local therapy to spine tumors has been shown to be effective in selected cases. Spinal radiosurgery (SRS) is an evolving radiotherapy regimen allowing for noninvasive, highly efficacious local treatment. The learning curve can compromise the results of any newly employed technology and should be studied to minimize its effects. In this paper the first 100 SRSs performed at several medical centers are presented and analyzed for the effects of the learning curve on outcome. METHODS A retrospective analysis was undertaken to evaluate data from patients treated with SRS at Sheba Medical Center and Assuta Medical Centers in the period from September 2011 to February 2016. Medical history, clinical and neurological findings, pathological diagnoses, SRS variables, complications, and follow-up data were collected and analyzed. Local control rates were calculated, and local treatment failure cases were qualitatively studied. RESULTS One hundred treatment sessions were performed for 118 lesions at 179 spinal levels in 80 patients. The complication rate was low and did not correlate with a learning curve. Mean follow-up time was 302 days, and the overall local control rate was 95%. The local control rate was dose dependent and increased from 87% (among 35 patients receiving a dose of 16 Gy) to 97% (among 65 patients receiving a dose of 18 Gy). The 6 treatment failure cases are discussed in detail. CONCLUSIONS Spinal radiosurgery is a safe and effective treatment. Comprehensive education of the treating team and continuous communication are essential to limit the effects of the learning curve on outcome.

Purpose: To evaluate salvage pelvic nodal radiation as an alternative to androgen deprivation therapy (ADT) in patients with biochemical failure and lymph node recurrence following salvage prostate fossa radiation., Methods: Six patients with biochemical failure and lymph node recurrence following prostate fossa radiation were treated with salvage pelvic nodal radiation therapy. A gross target volume was contoured using Choline PET/CT, CT, or MRI imaging. The clinical target volume included pelvic nodes. Avoidance structures were created using isodose lines from previous prostate fossa radiation plans. Radiation was delivered using IMRT or VMAT techniques. Failure was defined as a confirmed rise of prostate-specific antigen (PSA) over 0.2 ng/mL., Results: Four patients had presalvage PSA values <1 and 2 patients had PSAs >1. Dose to the clinical target volume was 54 to 60 Gy. The gross target volume dose was 60 to 73.6 Gy. One of the 2 patients with a high PSA received 6 months of concomitant ADT. Mean follow-up after RT for all patients was 24.9 months (range, 18.1 to 33.0 mo). All 5 patients with no ADT had significant PSA responses. PSA reduction was 80% (62% to 100%) of pre-RT PSA. At last follow-up, 2 patients with initial PSA<1 ng/mL remain free of biochemical progression at 33 and 20 months. Four patients have had PSA rise and meet criteria for failure. This included both patients with initial PSA values > 1. Duration of response before failure was 18.1 to 30.7 months. ADT for failure has been started in 1 patient. There was no grade ≥2 GI or GU toxicity., Conclusions: Salvage lymph node irradiation for patients with early biochemical recurrence and radiologic evidence of pelvic nodal metastases is well tolerated and associated with a durable biochemical response and may be an alternative to or may delay the need for ADT in some patients.

Purpose: Spine stereotactic radiosurgery (SRS) delivers an accurate and efficient high radiation dose to vertebral metastases in 1-5 fractions. We aimed to compare volumetric modulated arc therapy (VMAT) to static beam intensity modulated radiotherapy (IMRT) for spine SRS., Methods and Materials: Ten spine lesions of previously treated SRS patients were planned retrospectively using both IMRT and VMAT with a prescribed dose of 16 Gy to 100% of the planning target volume (PTV). The plans were compared for conformity, homogeneity, treatment delivery time, and safety (spinal cord dose)., Results: All evaluated parameters favored the VMAT plan over the IMRT plans. D min in the IMRT was significantly lower than in the VMAT plan (7.65 Gy/10.88 Gy, p < 0.001), the Dice Similarity Coefficient (DSC) was found to be significantly better for the VMAT plans compared to the IMRT plans (0.77/0.58, resp., p  value < 0.01), and an almost 50% reduction in the net treatment time was calculated for the VMAT compared to the IMRT plans (6.73 min/12.96 min, p < 0.001)., Conclusions: In our report, VMAT provides better conformity, homogeneity, and safety profile. The shorter treatment time is a major advantage and not only provides convenience to the painful patient but also contributes to the precision of this high dose radiation therapy.

Purpose: Pelvic irradiation is controversial in prostate cancer and has been associated with significant late toxicity, but may be beneficial in patients with high risk disease. To evaluate dose reduction to organs at risk (OAR), we compared volumetric intensity modulated arc therapy with hypofractionated concomitant integrated prostate boost (VMAT) to sequential 3-D conformal 4 field pelvis plan and prostate IMRT boost (Sequential IMRT)., Methods: The planning CT's of 20 consecutive high risk prostate cancer patients were utilized for this study. Dose planning using triple A algorithm (Varian Eclipse). CTV included prostate and proximal seminal vesicles. These were expanded by 6 mm for the PTV1 . Pelvic LN were delineated and expanded by 3 mm for the PTV2. Volume based equivalent dose at 2Gy/fx (EQD2) doses were calculated using alpha/beta ratios of 1.5 Gy for the prostate and 3 Gy for normal tissues. VMAT prescription was 73.6 Gy (EQD2-80 Gy) to PTV1 and 54.4 Gy to PTV2 (EQD2-50 Gy) in 32 fractions of 2.3 Gy and 1.7 Gy, respectively. Sequential prescription was 46 Gy to the pelvis and 34 Gy for IMRT boost to a total of 80 Gy in 40 fractions of 2 Gy each., Results: A significant reduction in mean dose was observed for rectum, bladder, bowel, femur head, and penile bulb for VMAT vs. Sequential IMRT (p<0.001) (table 1). Rectal V75 and V70 was 6.2% and 11.2% for VMAT and 13.6% and 19% for Sequential IMRT (p<0.001). Bowel V50 was 0.35 cm 3 vs. 24.1 cm 3 (p<0.001), respectively. The 98% isodose conformity index for the PTV was 1.44 for VMAT vs. 1.69 for Sequential IMRT (p<0.001)., Conclusions: VMAT with concomitant boost significantly reduced dose to OAR compared to Sequential IMRT, potentially leading to less late toxicity, while providing excellent target coverage and conformity. Furthermore, reduction of treatment planning time and both individual fraction and overall treatment delivery time inherent in this approach, offer significant advantages for both providers and patients., (© 2012 American Association of Physicists in Medicine.)

Objectives: To study interphysician variability of delineation of the prostatic fossa clinical target volume (pfCTV) to be irradiated in patients with residual or recurrent microscopic prostate cancer following radical prostatectomy and to estimate the risk for a geographical miss., Methods: Thirty-eight pfCTV were delineated on postradical prostatectomy computerized tomography scans of 8 patients by 5 observers. To estimate the risk of a geographical miss, a high risk volume (HRV) was defined and the percentage of "missed" HRV was calculated for each pfCTV., Results: Interphysician variability was considerable with a mean pfCTV of 39.09 cm (range, 11.8-72.5 cm). At least 25% of the HRV at the bladder neck/anastomosis and the retro-vesical space was excluded in 11 pfCTVs. The mean "missed" HRV was 27.5% (range, 2.3%-78.7%). A pfCTV of less than 30 cm was associated with a geographical miss in 66% of cases versus 17.2% for pfCTV of 30 cm or more (P = 0.006). Observer identity was significantly associated with excluded HRV (P = 0.03)., Conclusions: pfCTV delineation is subject to considerable interobserver variability associated with a significant risk of inadequate targeting of the anastomosis/bladder neck region and the retrovesical space. The failure to recognize regions at high risk for harboring microscopic disease may be due to a lack of familiarity with tissue redistribution following radical surgery, and a lack of literature-based guidelines for pfCTV delineation. A strategy to improve pfCTV delineation is proposed.

Purpose: Conformal radiotherapy (RT) has been used for all patients with orbital lymphoma treated at our institution since 1997. We retrospectively reviewed the charts of 23 consecutive patients to test the hypothesis that partial orbit RT is effective and less toxic than whole orbit RT., Methods and Materials: Twelve patients with limited lesions were treated to partial orbital volumes and 11 patients (1 with bilateral disease) with more extensive lesions received whole orbit RT. The dose was 20-30 Gy (median, 25.2 Gy) for 19 patients with low-grade lymphoma and 24-40 Gy (median, 39.6 Gy) for 5 patients with intermediate- to high-grade lymphoma. The follow-up was 12-68 months (median, 34 months)., Results: All patients had a complete response to RT. Intraorbital recurrence developed in previously uninvolved areas not included in the initial target volume in 4 patients (33%) treated with partial orbit RT. All were salvaged by repeat RT or surgery. No patient treated with whole orbit RT developed intraorbital recurrence. The acute and long-term toxicity was similar in both groups. All but 1 patient retained good vision., Conclusion: Patients with orbital lymphoma should be treated to the entire orbit. An effective dose of RT for low-grade lesions is 25 Gy, which results in minimal morbidity even when delivered to the entire orbit.