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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]

Radiation therapy is an effective treatment of primary brain tumors. post radiotherapy cognitive deterioration is a major concern. The hippocampus plays important roles in the consolidation of information from short-term memory to long-term memory, and spatial memory. Most of the focused is on the avoidance of radiation to the hippocampus grey matter. The primary purpose of this study is to shown that white matter tracts (memory fibers) of hippocampal function mapped by DTI can be delineate and incorporate into RT planning as an avoidance structure without compromising PTV coverage. In addition to the purpose of this study is to show that with that approach we can minimize damage to the brain thus preserving memory function and decrease cognitive decline secondary to brain radiotherapy. DTI Diffusion tensor imaging (DTI) is an MRI imaging method that allows for imaging of the random diffusion motion of water molecules inside brain's tissues. Integration of DTI into radiation treatment planning has been done in the past and was shown to be feasible and beneficial. This is a prospective trial of single cohort that been approved by the IRB. RT was delivered to a total dose of 54-60Gy in -27-30 fractions according to guidelines. During MRI simulation and before radiation therapy a diffuse sequence was performed. Two different radiation plans were performed by two different independent physicists. One with constrains on all memory fibers tract outside the PTV and one with only to the hippocampi as institution guidelines. In this trial we used the Montreal Cognitive Assessment for cognitive and memory evaluation. Recruitment was completed with 12 patients were analyzed for this analysis. The average age was 56 (42-71) with KPS>80. Dosimetrist analysis: The memory fibers and Hippocampi were successfully contoured in all 12 cases. Volumetric modulated arc therapy spared the memory avoidance structures; with the mean dose to the memory fibers structures was 15.2 Gy (range = 9.4-19.1 Gy) and a maximum dose (D0.03 cm3) range of 25.1-39.8 Gy. For the hippocampi Target coverage was achieved for all plans. For comparison a 2nd plan was created and analyzed with an independent physics without constrains to the Memory fibers. The mean dose was 18.4Gy (range = 18.1-26.9 Gy) and a maximum dose (D0.03 cm3) range of 43.4 Gy (40.1-55.6), P = 0.04 Cognitive analysis All 12 patients completed the MoCA test before the beginning of RT and 4 month after. The average score was 27.1 (23-30) and 26.4 (21-30) respectively, P -0.07. MRI planning using DTI to detect memory fibers and incorporate into RT planning using VMAT techniques allow for sparing of the hippocampi and the white fibers that connecting into and out to the hippocampus with plausibility for memory fibers avoidance without affecting PTV coverage. Phase 2 study will open soon with primary end point for cognitive preservation with new patient's cohort. [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: Radiation therapy (RT) is a critical treatment modality for both primary and metastatic brain tumors, yet ∼30% of patients experience cognitive decline post-RT. This cognitive toxicity is linked to low radiation doses affecting the hippocampal dentate gyrus. Hippocampal avoidance-whole brain RT combined with memantine has shown promising outcomes in preserving cognitive function and quality of life in patients with brain metastases. Nowadays, it is the standard of care for those with good performance status and no hippocampal metastases., Methods and Materials: We conducted a prospective trial approved by the institutional review board (SMC0307-23), including patients aged ≥18 years with primary brain tumors postresection or biopsy. Exclusion criteria included multifocal glioma crossing to the other hemisphere. RT was delivered to a total dose of 54 Gy in 30 fractions. Diffusion tensor imaging was performed to map hippocampal-associated white matter tracts. Using Eclipse treatment planning software, memory fiber tracts and hippocampi were contoured and integrated into RT planning. Dosimetric analyses compared 2 plans with memory fiber constraints and 1 without. The primary endpoints were safety and dosimetric feasibility., Results: Twelve patients with low-grade gliomas were included, and the contouring of memory fibers and hippocampi was successful. Volumetric modulated arc therapy (VMAT) treatment plans met-dose constraints for memory fibers, with an average mean dose of 10.1 Gy. The average Montreal Cognitive Assessment score before RT was 27.1 and 26.4 at 8 months post-treatment, with a P value of .07. Excluding 1 patient, the scores were 27.1 and 26.6, respectively (P = .13)., Conclusions: Magnetic resonance imaging planning using diffusion tensor imaging for memory fiber detection and incorporation into RT planning via VMAT techniques enables hippocampal and associated white fiber sparing, potentially preserving cognitive function. Preliminary cognitive data are promising, supporting the need for further validation in a larger cohort., (Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Refractory upper abdominal pain or lower back pain (retroperitoneal pain syndrome) related to celiac plexus involvement characterises pancreatic and other upper gastrointestinal malignancies and is an unmet need. We hypothesised that ablative radiation delivered to the celiac plexus would decrease pain., Methods: This multicentre, single-arm, phase 2 study was done at eight hospitals in five countries (Israel, Poland, Canada, the USA, and Portugal). Eligible patients aged 18 years or older with an average pain level of 5-10 on the Brief Pain Inventory short form (BPI-SF), an Eastern Cooperative Oncology Group performance status score of 0-2, and either pancreatic cancer or other tumours involving the celiac axis, received a single fraction of 25 Gy of external-beam photons to the celiac plexus. The primary endpoint was complete or partial pain response based on a reduction of the BPI-SF average pain score of 2 points or more from baseline to 3 weeks after treatment. All evaluable patients with stable pain scores were included in response assessment. The trial is registered with ClinicalTrials.gov, NCT03323489, and is complete., Findings: Between Jan 3, 2018, and Dec 28, 2021, 125 patients were treated, 90 of whom were evaluable. Patients were followed up until death. Median age was 65·5 years (IQR 58·3-71·8), 50 (56%) were female and 40 (44%) were male, 83 (92%) had pancreatic cancer, and 77 (86%) had metastatic disease. Median baseline BPI-SF average pain score was 6 (IQR 5-7). Of the 90 evaluable patients at 3 weeks, 48 (53%; 95% CI 42-64) had at least a partial pain response. The most common grade 3-4 adverse events, irrespective of attribution, were abdominal pain (35 [28%] of 125) and fatigue (23 [18%]). 11 serious adverse events of grade 3 or worse were recorded. Two grade 3 serious adverse events were probably attributed to treatment by the local investigators (abdominal pain [n=1] and nausea [n=1]), and nine were possibly attributed to treatment (seven were grade 3: blood bilirubin increased [n=1], duodenal haemorrhage [n=2], abdominal pain [n=2], and progressive disease [n=2]; and two were grade 5: gastrointestinal bleed from suspected varices 24 days after treatment [n=1] and progressive disease [advanced pancreatic cancer] 89 days after treatment [n=1])., Interpretation: Celiac plexus radiosurgery could potentially be a non-invasive palliative option for patients with retroperitoneal pain syndrome. Further investigation by means of a randomised comparison with conventional celiac block or neurolysis is warranted., Funding: Gateway for Cancer Research and the Israel Cancer Association., Competing Interests: Declaration of interests YRL reports receiving grant funding for this study from Gateway for Cancer Research and the Israel Cancer Association; has received research funding for other studies from Karyopharm Therapeutics, Checkmate Pharmaceuticals (purchased by Regeneron Pharmaceuticals), and Bristol-Myers Squibb; and has received honoraria from Roche Genetech, and has stock ownership in Protean Biodiagnostics. LAD reported being past president and chair of the American Society for Radiation Oncology; had a licensing agreement with Raysearch during the accrual for the present study; and has accepted honoraria from AstraZeneca. LSF reported his institution receiving payment from Gateway for Cancer Research; has clarified that he was at first chairman of the data and safety monitoring board for this trial, and later switched to be the statistician of the data and safety monitoring board; no separate payments were made to him or to his institution for this work. ASB reported having received an honorarium from Eisai. DADP reported having received payment or honoraria from the American Society of Clinical Oncology and travel support from the American Society for Radiation Oncology. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Purpose/objectives: Stereotactic body radiotherapy (SBRT) is an effective treatment for oligometastatic disease in multiple sites. However, the optimal radiation dose for long-term local control of adrenal metastases has yet to be determined. The aim of this study is to evaluate outcomes of adrenal SBRT and to evaluate factors that correlate with local control., Materials/methods: After IRB approval, a retrospective data review of patients treated with SBRT for adrenal metastases at a medical center in Israel between 2015 and 2021 was conducted. A biological effective dose was calculated using an alpha beta ratio of 10. Kaplan Meier and Cox regression were calculated using SPSS software to describe the hazard ratio for local control and survival., Results: 83 cases of adrenal SBRT were identified. The average age was 67 (range 42-92 years old). Non-small cell lung cancer was the primary site in 44 % of patients. A total of 70 % of the patients had oligometastatic disease (less than five lesions), and the rest were polymetastatic, responding to systemic therapy with oligo progression in the adrenal. The average gross tumor volume (GTV) was 42 ml. Respiratory control was applied in 88 % of cases; 49.3 % used 4-D/ITV, and 38.5 % used breath-hold or continuous positive airway pressure (CPAP) with free breathing. On multivariable analysis, Dose above 75 Gy (biological effective Dose) (HR = 0.41, p = 0.031), Dose above 8 Gy per fraction (HR = 0.53p = 0.038), and breath-holds or CPAP (HR = 0.65, p = 0.047) were significant for local control. From multivariable analysis, we computed a predicted nomogram curve using seven clinical parameters to evaluate local control odds., Conclusion: In this single institution series reported to date, we found unilateral adrenal SBRT safe, yet bilateral treatment harbors a risk of adrenal insufficiency. Biological effective Dose > 75 Gy (BED), motion management with breath-hold or CPAP, and Dose per fraction > 8 Gy were the enhanced local controls. We propose a nomogram to help in decision-making regarding total Dose and Dose per fraction when treating adrenal SBRT., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Introduction: Microsatellite stable metastatic colorectal cancer (MSS mCRC) is largely refractory to immune checkpoint inhibition. We hypothesized that a combination of intratumoral TLR9 agonist, radiosurgery and dual PD-1 and CTLA-4 blockade would induce a local focus of immune stimulation, evoking a systemic immune response., Patients and Methods: In this phase I single-institution study, patients with MSS mCRC were treated with a priming dose of s.c vidutolimod, 3 intratumoral injections of vidutolimod and radiosurgery, combined with nivolumab and ipilimumab. Cytokine levels were measured at baseline and at 7 (± 2) weeks. Patients were accrued to 4 consecutive cohorts: (1) Safety run-in without radiosurgery, (2) Radiosurgery prior to intratumoral therapy, (3) Radiosurgery prior to intratumoral therapy with a condensed timeline, and (4) Radiosurgery to extrahepatic lesion following completion of intratumoral therapy., Results: A total of 19 patients were accrued. Median age was 59 years (range 40-71), 68% were male, median number of previous systemic treatments was 3 (range 2-5). None of the patients responded, aside from 1 patient, attributed to high tumor mutational burden. Grade 3 liver toxicity was reported in 0%, 0%, 75%, and 17% in cohorts 1 to 4, respectively. Systemic levels of CXCL10 and IL-10 increased, with a median of 407 versus 78 pg/mL (P = .01), and 66 versus 40 pg/mL (P = .03), respectively., Conclusions: The combination of intratumoral vidutolimod, radiosurgery, nivolumab and ipilimumab was not found to be efficacious in MSS mCRC with liver metastases. The juxtaposition of liver irradiation and intratumoral vidutolimod injection was associated with high hepatic toxicity., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Refractory epigastric/midback pain is associated with locally advanced abdominal malignancies, especially pancreatic cancer. The pain is caused by tumor infiltration of the celiac plexus, a nerve network attached to the abdominal aorta. Contemporary palliative approaches are often inadequate. We hypothesized that ablative radiation targeted to the celiac plexus would alleviate this pain., Methods and Materials: We performed a single-arm prospective clinical trial (ClinicalTrials.gov identifier: NCT02356406). Eligible and evaluable patients had celiac pain of at least 5 out of 10 on the Numerical Rating Scale, completed treatment per protocol, and had at least 1 posttreatment visit. The entire retroperitoneal celiac plexus was irradiated with a single 25-Gy fraction. The primary endpoint was change in the Numerical Rating Scale 3 weeks posttreatment. Toxic effects and pain interference (as measured with the Brief Pain Inventory) were secondary endpoints., Results: For our study, 31 patients signed consent, and, of these, 18 patients were treated and evaluable. Median age was 68 years (range, 51-79); 89% of the patients had pancreatic cancer; the median Eastern Cooperative Oncology Group performance status was 1; and the median interval from initial diagnosis to treatment was 9 months (range, 1-36), and, in this interval, patients received a median of 1 systemic treatment line (range, 0-3). Acute toxicity was limited to grade 1 to 2. Three weeks after treatment, 16 patients (84%) reported decreased celiac pain, with median pain level falling from 6 out of 10 (interquartile range [IQR], 5.0-7.5) at baseline to 3 out of 10 (IQR, 1.0-4.3); six weeks after treatment, the Numerical Rating Scale number fell further to 2.8 out of 10 (IQR, 0-3.3; both P < .005 vs baseline), including 4 patients who reported complete eradication of their celiac pain. Total daily morphine milligram equivalents decreased from 59 pretreatment to 50 at 3 weeks, and from 50 to 45 at 6 weeks. Significant improvement was seen in pain-interference scores., Conclusions: Celiac plexus radiosurgery appears to alleviate cancer-related pain. An international multicenter phase 2 trial is currently accruing., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: In the current study we evaluated 68 Ga PSMA PET/ CT to measure local control of bone metastasis in oligometastatic prostate cancer patients treated with SBRT., Materials and Methods: After the institutional review board approval, a retrospective review of medical records of consecutive prostate cancer patients treated between 2014 and 2018 was conducted. Only medical records of patients that were treated with SBRT for bone metastasis and had pre-and post-SBRT 68 Ga PSMA PET/CT scans were included in our study. Data extracted from the medical files included patient-related (age), disease-related (Gleason score, site of metastasis), and treatment-related factors and outcomes., Results: During the study period, a total of 12 patients (15 lesions) were included, with a median age of 73 years. The median follow-up was 26.5 months (range 13-45 months). Median time of 68 Ga PSMA PET/ CT follow up was 17.0 months (range 3-39 months). The median pre-treatment PSA was 2 ng/mL (range 0.56-44 ng/mL) vs . post treatment PSA nadir of 0.01 ng/mL (0.01-4.32) with a median time to nadir of 7 months (range, 2-12). Local control was 93% during the follow up period and there was correlation with PS MA avidity on PE T. None patients developed recurrences in the treated bone. None of the patients had grade 3 or more toxicities during follow-up., Conclusions: SBRT is a highly effective and safe method for treatment of prostate cancer bone metastases. More studies are required to determine if SBRT provides greater clinical benefit than standard fractionation for oligometastatic prostate cancer patients. 68 Ga PSMA PET/CT should be further investigated for delineation and follow-up., Competing Interests: Conflict of interest None declared., (© 2021 Greater Poland Cancer Centre.)

Purpose: This study aimed to study the impact of continuous positive airway pressure (CPAP) on chest anatomy and tumor motion in patients receiving radiation therapy., Methods and Materials: Patients with primary or secondary lung tumors, left-sided breast cancer, or liver metastases referred for radiation therapy were trained to breathe with a CPAP device using a face mask to a maximal pressure of 15 cm H 2 O. Three- and 4-dimensional computed tomography simulation was performed twice for each patient: once with free breathing (FB) and again using CPAP. Volumetric and dosimetric parameters of treatment plans were compared., Results: Forty-nine patients were enrolled, of whom 6 withdrew consent before simulation and 3 withdrew because of discomfort. Thus, a total of 40 patients were analyzed. Twenty-seven patients (67.5%) were treated with CPAP based on confirmation of the volumetric or dosimetric benefit of CPAP. Mean lung volume increased by 37% (P < .001). The mean augmentation was 1283 ± 1128 cm 3 (CPAP vs FB; P = .0006) in patients with normal lung function tests and 719 ± 341 cm 3 (P = .003) in patients with a restrictive pattern. Increased lung volume was independent of age, body mass index, sex, chronic obstructive pulmonary disease, smoking status, and heart disease. Tumor motion in the lung was decreased as reflected in a mean reduction of planning target volume by 19% (P < .001). The greatest reduction of tumor trajectory and planning target volume occurred in tumors in the lower lung, particularly in the range of up to 6 cm above the dome of the diaphragm. The mean lung dose was reduced by 15%, lung V20 by 20%, lung V5 by 11%, and heart V5 by 16% (P < .01)., Conclusions: In this prospective trial, the use of CPAP was associated with significant volumetric and dosimetric benefits compared with FB. CPAP was safe, simple to implement, and well tolerated by most patients, and it should be studied further as a method to reduce the risk of lung and heart toxicity., (Copyright © 2021 Elsevier Inc. All rights reserved.)

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.

Objectives: Anatomic changes may occur during chemoradiation treatment for lung cancers, requiring adaptive replanning. Here we characterize these cases., Methods: We retrospectively studied lung cancer cases that underwent resimulation and adaptive replanning during 1/2016-3/2019. We compared first and second CT-simulation regarding tumor location, timing of change, tumor volume, anatomical alteration and change in simulation technique. We also compared dosimetric parameters between the plans, recorded local control, and overall survival outcomes., Results: Out of 281 patients, 58 underwent replanning (20.6%). Histology included small cell (22.4%) and non-small cell (77.6%). Stage III was in 91.4%. Mean radiation dose of 59.4 Gray (Gy) (range 50-66Gy).Tumor location was peribronchial in 53.5%. Timing of replanning was in the first, second and final third of the treatment course in 26%, 43% and 31% respectively. Changes in gross tumor volume were observed in 74%; mean gross tumor volume was 276.7cc vs 192.7 cc (first vs second simulation, p = 0.001). Anatomical changes were identified in 35.4% including pleural fluid accumulation, atelectasis or pneumothorax alteration. Change in simulation technique was performed in 25.9%, including breath-hold or continuous positive airway pressure.Changes in dosimetric parameters when the same technique was used: lung V20Gy 26% (standard deviation, SD 7.6) vs 25.3% (SD 6.6) ( p = 0.36), mean lung dose 15.1 Gy (SD 3.7) vs 14.7Gy (SD 3.3) ( p = 0.23), heart V40Gy 10.2% (SD13) vs 7.2% (SD 9.8) ( p = 0.037). When simulation technique changed: lung V20Gy 30.8% (SD 8.2) vs 27.3% (SD 8) ( p = 0.012), mean lung dose 17.3 Gy (SD 4.4) vs 15.3 Gy (SD 3.8) ( p = 0.007), heart V40Gy 11.1% (SD 14.7) vs 6.5% (SD 6.7) ( p = 0.014).2 year local control was 60.7% (95% confidence interval, 34.5-79.2%), and median overall survival was 19.7 months., Conclusion: Adaptive replanning of radiation was performed in a fifth of locally advanced lung cancer patients. In most cases tumor volume decreased, or atelectasis resolved, causing mediastinal shifts, which, if unidentified and left uncorrected, may have led to local failure and increased toxicity. The heart V40Gy was reduced significantly in all cases, but significant reduction in lung doses was evident only if simulation technique was altered., Advances in Knowledge: In locally advanced lung cancer image-guidance with cone beam CT can detect significant mediastinal shifts and gross tumor volume changes that raise the need for adaptive replanning. Image guidance-triggered adaptive replanning should be added to the armament of advanced radiation treatment planning in locally advanced lung cancer.

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: Adjuvant radiotherapy for breast cancer reduces local recurrence and improves survival. In patients with left sided breast cancer, anterior heart position or medial tumor location may cause inadequate breast coverage due to heart shielding. Respiration gating using the Real-time Position Management (RPM) system enables pushing the heart away from the tangential fields during inspiration, thus optimizing the treatment plan., Objectives: To compare breathing inspiration gating (IG) techniques with free breathing (FB), focusing on breast coverage., Methods: The study comprised 49 consecutive patients with left sided breast cancer who underwent lumpectomy and adjuvant radiation. RPM was chosen due to insufficient breast coverage caused by an anterior heart position or medial lumpectomy cavity. FB and IG computed tomography simulations were generated for each patient. Breast (PTVbreast) and lumpectomy cavity (CTVlump) were defined as the target areas. Optimized treatment plans were created for each scan. A dosimetric comparison was made for breast coverage and heart and lungs doses., Results: PTVbreast V95% and mean dose (Dmean) were higher with IG vs. FB (82.36% vs. 78.88%, P = 0.002; 95.73% vs. 93.63%, P < 0.001, respectively). CTVlump V95% and Dmean were higher with IG (98.87% vs. 88.92%, P = 0.001; 99.14% vs. 96.73%, P = 0.003, respectively). The cardiac dose was lower with IG. The IG left lung Dmean was higher. No statistical difference was found for left lung V20., Conclusions: In patients with suboptimal treatment plans due to anterior heart position or medial lumpectomy cavity, RPM IG enabled better breast/tumor bed coverage and reduced cardiac doses.

Background: Stereotactic ablative radiation therapy (SABR) is the application of a very high radiation dose to a small treatment volume. It is the new standard of care in medically inoperable early-stage lung cancer., Objectives: To report the outcomes of SABR in stage I lung cancer at Sheba Medical Center since its introduction in 2009., Methods: We conducted a retrospective chart review of patients with stage I lung cancer treated during the period 2009-2015. Survival status was retrieved from the electronic medical records and confirmed with the national registry. Local failure was defined as increased FDG uptake on PETCT scan within a 2 cm radius of the treated region. Toxicity was estimated from medical records and graded according to common toxicity criteria for adverse events (CTCAE) version 4.03. Overall survival and local control were estimated by the Kaplan-Meier method., Results: During the study period 114 patients were treated for 122 stage I lung cancer lesions. Median follow-up time was 27 months (range 8.2-69.5 months), median age was 76 years. Eighty-two percent of the tumors were stage IA (size ≤ 3 cm). Median survival was 46 months; estimated 3 year overall survival was 59% (95%CI 47-69%) and local control was 88% (95%CI 78-94%). Toxicity included chest wall pain in 8.4% of patients, rib fracture in 0.9%, grade 1-2 pneumonitis in 12%, grade 3 in 12% and grade 5 (death) in 0.9%., Conclusions: SABR has been successfully implemented at Sheba Medical Center for the treatment of stage I lung cancer in inoperable patients. It is associated with excellent local control, minor toxicity and an acceptable overall survival.

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: 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.