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Introduction: Medically refractory epilepsy (MRE) occurs in about 30 % of patients with epilepsy, and the treatment options available to them have evolved over time. The classic treatment for medial temporal lobe epilepsy (mTLE) is anterior temporal lobectomy (ATL), but an initiative to find less invasive options has resulted in treatments such as neuromodulation, ablative procedures, and stereotactic radiosurgery (SRS). SRS has been an appealing non-invasive option and has developed an increasing presence in the literature over the last few decades. This article provides an overview of SRS for MRE with two example cases, and we discuss the optimal technique as well as the advantages, alternatives, and risks of this therapeutic option., Cases: We present two example cases of patients with MRE, who were poor candidates for invasive surgical treatment options and underwent SRS. The first case is a 65-year-old female with multiple medical comorbidities, whose seizure focus was localized to the left temporal lobe, and the second case is a 19-year-old male with Protein C deficiency and medial temporal lobe sclerosis. Both patients underwent SRS to targets within the medial temporal lobe, and both achieve significant improvements in seizure frequency and severity., Discussion: SRS has generally been shown to be inferior to ATL for seizure reduction in medically refractory mTLE. However, there are patients with epilepsy for which SRS can be considered, such as patients with medical comorbidities that make surgery high risk, patients with epileptogenic foci in eloquent cortex, patients who have failed to respond to surgical management, patients who choose not to undergo surgery, and patients with geographic constraints to epilepsy centers. Patients and their physicians should be aware that SRS is not risk-free. Patients should be counseled on the latency period and monitored for risks such as delayed cerebral edema, visual field deficits, and radiation necrosis., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: Meningiomas represent the most common primary tumor of the central nervous system. Current treatment options include surgical resection with or without adjuvant radiation therapy (RT), definitive RT, and observation. However, the radiation dose, fractionation, and margins used to treat patients with WHO grade 2 meningiomas, which account for approximately 20% of all meningiomas, are not clearly defined, and deciding on the optimal treatment modality can be challenging owing to the lack of randomized data., Methods and Materials: In this manuscript, 3 cases of patients with WHO grade 2 meningiomas are presented with descriptions of treatment options after gross total resection, subtotal resection, and previous irradiation. Treatment recommendations were compiled from 9 central nervous system radiation oncology and neurosurgery experts from The Radiosurgery Society, and the consensus of treatment recommendations is reported., Results: Both conventional and stereotactic RT are treatment options for WHO grade 2 meningiomas. The majority of prospective data in the setting of WHO grade 2 meningiomas involve larger margins. Stereotactic radiosurgery/hypofractionated stereotactic RT are less appropriate in this setting. Conventionally fractionated RT to at least 59.4 Gy is considered standard of care with utilization of preoperative and postoperative imaging to evaluate the extent of disease and possible osseous involvement. After careful discussion, stereotactic radiosurgery/hypofractionated stereotactic RT may play a role for the subset of patients who are unable to tolerate the standard lengthy conventionally fractionated treatment course, for those with prior RT, or for small residual tumors. However, more studies are needed to determine the optimal approach., Conclusions: This case-based evaluation of the current literature seeks to provide examples for the management of grade 2 meningiomas and give examples of both conventional and stereotactic RT., Competing Interests: Disclosures A.S. has grants/contracts from Elekta AB and Seagen through his institution, as well as consulting fees from Varian, Elekta, and BrainLAB. He also has honoraria from AstraZeneca, Elekta AB, Varian, BrainLAB, and Seagen. He has leadership roles in the International Stereotactic Radiosurgery Society as well as the SO Spine Knowledge Forum Tumor. He is a member of the Elekta MR Linac Research Consortium, the Elekta Oligometastases Group, and the Elekta Gamma Knife Icon Group. I.G. has a leadership role on the ASTRO and Radiosurgery Society BOD. He receives honoraria for lectures and from Accuray, Inc. E.C. has travel support for travel to ICOTEC meetings. F.E. has honoraria and travel support from ZAP Surgical Systems, Inc. G.G.K. has consulting fees from Varian Medical Systems. J.P. has grants/contracts from Genentech, NIH R702, NIH R01CA269948. He also has honoraria from Varian Medical Systems, Novocure, ICOTEC, and Carbofix. He is on the Novocure advisory board. He has a leadership role in the Spine Therapy Society as a Steering Committee Member. J.K. has consulting fees from Reflexion, ICOTEC, CarboFix, Accuray, Varian, Elekta, ViewRay, and Brainlab. He has honoraria from Varian, ICOTEC, Carbofix, Acurray, BrainLab, ViewRay. He has a leadership role in ASTRO, RSS, and the Accuray Exchange Community. K.R. has grants/contracts from Accuray, Canon, and ICOTEC. She receives an honoraria from Accuray.. She receives support for attending meetings from Elekta AB, Accuray, Brainlab, RSS, and AAPM. She has a radiogenomics patent shared with Canon under development. She participates on the BioMimetix Board. She is a CNS track chair leader for the ASTRO education committee. M.S. has consulting fees from Hyperfine, Inc. He receives support for attending meetings from the World Society for Stereotactic and Functional Neurosurgery. He participates on the board for Alpheus, Inc. He is the president of the Brain Tumor Foundation. He is a stock holder for Hyperfine, Inc. S.C. receives payments from GE Health care, Varian Medical Systems, and Blue Earth Diagnostics. S.L. has research funding from Kuni Foundation and Hutchinson Center as Lead Academic Participating Site. He receives support for attending the Japanese Society for Radiation Oncology (JASTRO). He has a leadership role in the Radiosurgery Society and American College of Radiology. All other authors have no disclosures., (Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

The use of radiation therapy (RT) for pancreatic cancer continues to be controversial, despite recent technical advances. Improvements in systemic control have created an evolving role for RT and the need for improved local tumor control, but currently, no standardized approach exists. Advances in stereotactic body RT, motion management, real-time image guidance, and adaptive therapy have renewed hopes of improved outcomes in this devastating disease with one of the lowest survival rates. This case-based guide provides a practical framework for delivering stereotactic body RT for locally advanced pancreatic cancer. In conjunction with multidisciplinary care, an intradisciplinary approach should guide treatment of the high-risk cases outlined within these guidelines for prospective peer review and treatment safety discussions., Competing Interests: Disclosures Christopher H. Crane receives consulting fees from Trisalis and honoraria from Elekta and has stock options in Oncternal. Karyn A. Goodman serves on the advisory board of RenovoRx and leadership in the NCI GI Steering Committee. Percy Lee receives consulting fees from Varian, ViewRay, AstraZeneca, Genentech, Johnson & Johnson, RTOG Foundation, honoraria from Varian, ViewRay, AstraZeneca, and travel support from Radiosurgery Society; serves on the advisory board for Genentech, ViewRay, AstraZeneca, Roche, and leadership of Radiosurgery Society, ASTRO. Michael D. Chuong receives grants, consulting fees, honoraria, and travel support from ViewRay, and serves on the advisory board of ViewRay., (Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: Data informing the safety, efficacy, treatment logistics, and dosimetry of stereotactic body radiation therapy (SBRT) for lung tumors has primarily been derived from patients with favorably located solitary tumors. SBRT is now considered a standard-of-care treatment for inoperable early-stage non-small cell lung cancer and lung metastases, and therefore extrapolation beyond this limited foundational patient population remains an active source of interest., Materials and Methods: This case-based discussion provides a practical framework for delivering SBRT to challenging, yet frequently encountered, cases in radiation oncology. The cases highlighted herein include the use of SBRT for ultracentral tumors, multiple tumors, and re-irradiation. Patient characteristics, fractionation, prescription dose, treatment technique, and dose constraints were discussed. Relevant literature to these cases was summarized to provide a framework for the treatment of similar patients., Results: Treatment of challenging cases with lung SBRT requires many considerations, including treatment intent, fractionation selection, tumor localization, and plan optimization. In such scenarios, patient selection is critical to understanding the risk-benefit profile of an SBRT approach despite significant advances in delivery techniques and safety., Conclusions: A case-based discussion was developed by the Radiosurgery Society to provide a practical guide to the common challenging scenarios noted above affecting patients with lung tumors. A multidisciplinary approach should guide the treatment of such cases to maximize the therapeutic window., Competing Interests: Declaration of competing interest Dr Slotman receives speaker fees from Varian Medical Systems. Dr Ladbury has research grant funding from RefleXion Medical and AstraZeneca. Dr Lee receives consulting fees (from Varian, ViewRay, AstraZeneca, Genentech, Johnson & Johnson, Roche, and RTOG foundation), honoraria (from Varian, ViewRay, and AstraZeneca), travel support (from Radiosurgery Society), serves in an advisory role (to Genentech, ViewRay, AstraZeneca, Roche), and has leadership roles (in Radiosurgery Society and ASTRO)., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Spinal stereotactic body radiation therapy (SBRT) has become the standard of care in management of patients with limited sites of metastatic disease, radioresistant histologies, painful vertebral metastases with long life expectancy and cases of reirradiation. Our case-based guidelines aim to assist radiation oncologists in the appropriate utilization of SBRT for common, yet challenging, cases of spinal metastases., Methods and Materials: Cases were selected to include scenarios of large volume sacral disease with nerve entrapment, medically inoperable disease abutting the thecal sac, and local failure after prior SBRT. Relevant literature was reviewed, and areas requiring further investigation were discussed to offer a framework for evidence-based clinical practice., Results: Spinal SBRT can be effectively delivered in challenging cases following multidisciplinary discussion by using a methodical approach to patient selection, appropriate dose selection, and adherence to evidence-based dose constraints., Conclusions: The Radiosurgery Society's case-based practice review offers guidance to practicing physicians treating technically challenging SBRT candidate patients with spinal metastases., Competing Interests: Disclosures Anubhav G. Amin reports receiving consulting fees and payment for lectures from Globus. Samuel Chao reports payment for travel, honoraria, and research support from Blue Earth Diagnostics; and honoraria from GE Healthcare and Varian Medical Systems. Matthew Foote reports research grant from Elekta; consulting fees and honoraria from Varian and Elekta; and leadership role with Stereotactic Interest Group of Australasia. Matthias Guckenberger reports grants from ViewRay, Siemens Healthineers, and Astra Zeneca; consulting fees and honoraria from Astra Zeneca; and leadership role with ESTRO. Daniel Koffler reports internal departmental support for attending meetings; patent for Chimeric Immunomagnetic Nanosensors for cancer stem cell imaging; and leadership role in ESTRO workshop group in spatially fractionated RT. Simon Lo reports grant funding from Kuni Foundation, Hutchinson Center, and Elekta; has travel support from the Japanese Society for Radiation Oncology (JASTRO); and serves as member of the Board of Directors and National Medical Director of the Distinction in Practice in Stereotatic Radiotherapy Program for the Radiosurgery Society and Alternate Councilor for the American College of Radiology. Kristin J. Redmond reported receiving research support from Accuray, Canon, and Icotec; participating on a data and safety monitoring board for BioMimetix; has travel support from Icotec and Brainlab; honorarium from Accuray; and patent pending with Canon. Daniel Lubelski reports consulting fees from Carbofix, Mindset Medical, and Dillon Technologies. Arjun Sahgal has received research grants from Elekta AB, Varian, Seagen, and Brainlab; is an advisor/consultant with Varian, Elekta (Gamma Knife Icon), and Brainlab; has received honoraria for past educational seminars from AstraZeneca, Elekta AB, Varian, Brainlab, Cerapedics, Seagen, and Carbo FIX; is a vice president of the International Stereotactic Radiosurgery Society; is a cochair of the AO Spine Knowledge Forum Tumor, belongs to the Elekta MR-Linac Research Consortium; is a Clinical Steering Committee member; and chairs the Elekta Oligometastases Group and the Elekta Gamma Knife Icon Group. Shankar Siva received salary support from Cancer Council Victoria via the Colebatch Fellowship; grants or contracts from Varian, Bayer Pharmaceuticals, and Merck Sharp & Dohme; payment or honoraria for lectures, presentations, speaker's bureaus, manuscript writing, or educational events from AstraZeneca, Varian, Roche Pharmaceuticals, and Telix Pharmaceuticals; a leadership or fiduciary role on the American Society of Radiation Oncology Science Council and the Advanced Radiotherapy Techniques committee of the International Association for the Study of Lung Cancer; and is on the board of directors of the Radiosurgery Society, within the past 36 months. Balamurugan Vellayappan reports honoraria from Elekta and support for travel from Brainlab. The other authors declare no conflicts of interest. Artificial Intelligence was not utilized in this effort., (Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Head and Neck Squamous Cell Carcinoma (HNSCC) comprises a diverse group of tumors with variable treatment response and prognosis. The tumor microenvironment (TME), which includes microbiome and immune cells, can impact outcomes. Here, we sought to relate the presence of specific microbes, gene expression, and tumor immune infiltration using tumor transcriptomics from The Cancer Genome Atlas (TCGA) and associate these with overall survival (OS). RNA sequencing (RNAseq) from HNSCC tumors in TCGA was processed through the exogenous sequences in tumors and immune cells (exotic) pipeline to identify and quantify low-abundance microbes. The detection of the Papillomaviridae family of viruses assessed HPV status. All statistical analyses were performed using R. A total of 499 RNAseq samples from TCGA were analyzed. HPV was detected in 111 samples (22%), most commonly Alphapapillomavirus 9 (90.1%). The presence of Alphapapillomavirus 9 was associated with improved OS [HR = 0.60 (95%CI: 0.40-0.89, p  = .01)]. Among other microbes, Yersinia pseudotuberculosis was associated with the worst survival (HR = 3.88; p  = .008), while Pseudomonas viridiflava had the best survival (HR = 0.05; p  = .036). Microbial species found more abundant in HPV- tumors included several gram-negative anaerobes. HPV- tumors had a significantly higher abundance of M0 ( p  < .001) and M2 macrophages ( p  = .035), while HPV+ tumors had more T regulatory cells ( p  < .001) and CD8+ T-cells ( p  < .001). We identified microbes in HNSCC tumor samples significantly associated with survival. A greater abundance of certain anaerobic microbes was seen in HPV tumors and pro-tumorigenic macrophages. These findings suggest that TME can be used to predict patient outcomes and may help identify mechanisms of resistance to systemic therapies.

Background and purpose: Proton therapy has been shown to provide dosimetric benefits in comparison with IMRT when treating prostate cancer with whole pelvis radiation; however, the optimal proton beam arrangement has yet to be established. The aim of this study was to evaluate three different intensity-modulated proton therapy (IMPT) beam arrangements when treating the prostate bed and pelvis in the postoperative setting. Materials and Methods: Twenty-three post-prostatectomy patients were planned using three different beam arrangements: two-field (IMPT 2 B) (opposed laterals), three-field (IMPT 3 B) (opposed laterals inferiorly matched to a posterior-anterior beam superiorly), and four-field (IMPT 4 B) (opposed laterals inferiorly matched to two posterior oblique beams superiorly) arrangements. The prescription was 50 Gy radiobiological equivalent (GyE) to the pelvis and 70 GyE to the prostate bed. Comparisons were made using paired two-sided Wilcoxon signed-rank tests. Results: CTV coverages were met for all IMPT plans, with 99% of CTVs receiving ≥ 100% of prescription doses. All organ at risk (OAR) objectives were met with IMPT 3 B and IMPT 4 B plans, while several rectum objectives were exceeded by IMPT 2 B plans. IMPT 4 B provided the lowest doses to OARs for the majority of analyzed outcomes, with significantly lower doses than IMPT 2 B +/- IMPT 3 B for bladder V30-V50 and mean dose; bowel V15-V45 and mean dose; sigmoid maximum dose; rectum V40-V72.1, maximum dose, and mean dose; femoral head V37-40 and maximum dose; bone V40 and mean dose; penile bulb mean dose; and skin maximum dose. Conclusion: This study is the first to compare proton beam arrangements when treating the prostate bed and pelvis. four-field plans provided better sparing of the bladder, bowel, and rectum than 2- and three-field plans. The data presented herein may help inform the future delivery of whole pelvis IMPT for prostate cancer.

Cisplatin, one of the most ototoxic anti-neoplastic agents, causes permanent hearing loss in up to 90% of patients. We assessed ototoxicity rates and prospectively collected audiologic outcomes of patients receiving low-dose or high-dose cisplatin with concurrent cochlear-sparing intensity-modulated radiation therapy (IMRT). Patients with head and neck squamous cell carcinoma (HNSCC) receiving definitive or adjuvant cisplatin-based chemoradiotherapy (CRT) were analyzed. Cisplatin was administered either in low doses weekly (40 mg/m 2 ) for up to seven doses or in high doses triweekly (100 mg/m 2 ) for up to three doses. Cochlear-sparing IMRT was delivered in all cases. Audiologic data were prospectively collected before, during, and after treatment completion. The primary endpoint was a hearing change grade of ≥3 after CRT completion. Of the 96 HNSCC patients evaluated, 69 received weekly cisplatin and 58 received definitive CRT. Of patients receiving weekly cisplatin, 13% developed ≥G3 ototoxicity vs. 56% of patients who received triweekly cisplatin ( p < 0.001). In multivariable modeling, the cisplatin dose schedule remained significant (OR: 8.4, 95%CI: 2.8-27.8, p < 0.001) for risk of severe irreversible ototoxicity. Triweekly cisplatin CRT significantly increased the ≥G3 severe irreversible ototoxicity risk compared to low-dose weekly cisplatin, irrespective of the cumulative cisplatin dose, even with the use of cochlear-sparing IMRT. No significant difference in oncologic outcomes was observed between the two schedules.

Background: Oncologic surgical resection is the standard of care for extremity and truncal soft tissue sarcoma (STS), often accompanied by the addition of pre- or postoperative radiation therapy (RT). Preoperative RT may decrease the risk of joint stiffness and fibrosis at the cost of higher rates of wound complications. Hypofractionated, preoperative RT has been shown to provide acceptable outcomes in prospective trials. Proton beam therapy (PBT) provides the means to decrease dose to surrounding organs at risk, such as the skin, bone, soft tissues, and adjacent joint(s), and has not yet been studied in patients with extremity and truncal sarcoma., Methods: Our study titled "PROspective phase II trial of preoperative hypofractionated protoN therapy for extremity and Truncal soft tissue sarcOma (PRONTO)" is a non-randomized, prospective phase II trial evaluating the safety and efficacy of preoperative, hypofractionated PBT for patients with STS of the extremity and trunk planned for surgical resection. Adult patients with Eastern Cooperative Group Performance Status ≤ 2 with resectable extremity and truncal STS will be included, with the aim to accrue 40 patients. Treatment will consist of 30 Gy radiobiological equivalent of PBT in 5 fractions delivered every other day, followed by surgical resection 2-12 weeks later. The primary outcome is rate of major wound complications as defined according to the National Cancer Institute of Canada Sarcoma2 (NCIC-SR2) Multicenter Trial. Secondary objectives include rate of late grade ≥ 2 toxicity, local recurrence-free survival and distant metastasis-free survival at 1- and 2-years, functional outcomes, quality of life, and pathologic response., Discussion: PRONTO represents the first trial evaluating the use of hypofractionated PBT for STS. We aim to prove the safety and efficacy of this approach and to compare our results to historical outcomes established by previous trials. Given the low number of proton centers and limited availability, the short course of PBT may provide the opportunity to treat patients who would otherwise be limited when treating with daily RT over several weeks. We hope that this trial will lead to increased referral patterns, offer benefits towards patient convenience and clinic workflow efficiency, and provide evidence supporting the use of PBT in this setting., Trial Registration: NCT05917301 (registered 23/6/2023)., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)