Comprehensive assessment of proton plans with three different beam delivery systems for multiple brain metastases.

Purpose: To compare plan quality among photon volumetric arc therapy (VMAT), Gamma Knife, and three different proton beam modalities. Methods: Fifty-five brain lesions from 20 patients were planned with three different proton spot size ranges of cyclotron-generated proton beams, CPBs (spot size σ: 2.7-7.0 mm), linear accelerator proton beams, LPBs (σ: 2.9-5.5 mm), and linear accelerator proton minibeams, LPMBs (σ: 0.9-3.9 mm), with and without apertures and compared against photon VMAT and Gamma Knife plans. Dose coverage to each lesion for each proton and photon plan was set to 99% of the GTV receiving the prescription (Rx) dose. All proton plans used ±2 mm setup uncertainty and ±2% range uncertainty in robust evaluation to achieve V100%Rx > 95% of the GTV. Apertures were applied to proton beams irradiating tumors <1 cm3 volume and located <2.5 cm depth. Conformity index (CI), gradient index (GI), V12 Gy, V4.5 Gy, and mean brain dose were compared across all plan types. The Wilcoxon signed rank test was utilized to determine statistical significance of dosimetric results compared between photon and proton plans. Results: When compared to CPB generated plans, average CI and GI were significantly better for the LPB and LPMB plans. Aperture-based IMPT plans showed improvement from Gamma Knife for all dosimetric metrics. Aperture-based IMPT plans also showed improvement in all dosimetric metrics for shallow tumors (d < 2.5 cm) when compared with non-aperture-based plans. Conclusion: The LPB and LPMB stand as excellent alternatives to CPB or photon therapy and significantly increase the preservation of normal tissue.

A Case-based Guide for World Health Organization (WHO) Grade 2 Meningioma Radiosurgery and Radiation Therapy from The Radiosurgery Society.

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.

Effective and Successful Control of Symptomatic Vertebral Hemangiomas With Epidural Extension Using Stereotactic Spine Radiosurgery.

BACKGROUND AND OBJECTIVES: We present our experience in the management of symptomatic vertebral hemangiomas with epidural extension (SVHEE) using spine stereotactic radiosurgery (SSRS). METHODS: An Institutional Review Board approved retrospective review of all SVHEE patients treated with SSRS at our institution (2007-2022) was performed. Baseline patient demographics, clinical presentation, lesion volume, and Bilsky grade (to directly evaluate the epidural component) were determined. Clinical and radiographic response and treatment outcomes were subsequently evaluated at first (∼6 months) and final follow-up. RESULTS: Fourteen patients with SVHEE underwent SSRS (16-18 Gy/1-fraction); the mean follow-up was 24 months. The median lesion volume (cc) was 36.9 (range: 7.02-94.1), 31.5 (range: 6.53-69.7), and 25.15 (range: 6.01-52.5) at pre-SSRS, first, and final follow-up, respectively. Overall volume reduction was seen in the last follow-up in all 14 patients, median 29.01% (range: 6.58%-71.58%). Bilsky score was stable or improved in all patients at the last follow-up when compared with pre-SSRS score. Patients who underwent both surgical decompression and SSRS (n = 9): 8 had improved myelopathic symptoms and pain and 1 had stable radiculopathy postintervention. In the 5 patients treated with SSRS monotherapy, 2 had stable radicular pain and the other 3 improved pain and numbness. No patients experienced adverse outcomes. CONCLUSION: To our knowledge, this represents the largest series of SVHEE patients treated with SSRS, either as monotherapy or part of a multimodal/separation surgery treatment approach. We demonstrate that SSRS represents a potentially safe and effective treatment option in these patients. However, larger prospective studies and longer follow-ups are necessary to further assess the role, durability, and toxicity of SSRS in the management of these patients.

Phase I trial of dose escalation for preoperative stereotactic radiosurgery for patients with large brain metastases.

BACKGROUND: Single session stereotactic radiosurgery (SRS) or surgical resection alone for brain metastases larger than 2 cm results in unsatisfactory local control. We conducted a phase I trial for brain metastases(>2cm) to determine the safety of preoperative SRS at escalating doses. METHODS: Radiosurgery dose was escalated at 3 Gy increments for 3 cohorts based on maximum tumor dimension starting at: 18 Gy for >2-3 cm, 15 Gy for >3-4 cm, and 12 Gy for >4-6 cm. Dose limiting toxicity (DLT) was defined as grade III or greater acute toxicity. RESULTS: A total of 35 patients/36 lesions were enrolled. For tumor size >2-3 cm, patients were enrolled up to the second dose level (21 Gy); for >3-4 cm and >4-6 cm cohorts the third dose level (21 Gy and 18 Gy, respectively) was reached. There were 2 DLTs in the >3-4 cm arm at 21Gy. The maximum tolerated dose (MTD) of SRS for >2-3 cm was not reached; and was 18 Gy for both >3-4 cm arm and >4-6 cm arm. With a median follow-up of 64.0 months, the 6- and 12-month local control rates were 85.9% and 76.6%, respectively. One patient developed grade 3 radiation necrosis at 5 months. The 2-year rate of leptomeningeal disease (LMD) was 0%. CONCLUSION: Preoperative SRS with dose escalation followed by surgical resection for brain metastases greater than 2 cm in size demonstrates acceptable acute toxicity. The phase II portion of the trial will be conducted at the maximum tolerated SRS doses.

The dilemma of radiation necrosis from diagnosis to treatment in the management of brain metastases.

Radiation therapy with stereotactic radiosurgery (SRS) or whole brain radiation therapy is a mainstay of treatment for patients with brain metastases. The use of SRS in the management of brain metastases is becoming increasingly common and provides excellent local control. Cerebral radiation necrosis (RN) is a late complication of radiation treatment that can be seen months to years following treatment and is often indistinguishable from tumor progression on conventional imaging. In this review article, we explore risk factors associated with the development of radiation necrosis, advanced imaging modalities used to aid in diagnosis, and potential treatment strategies to manage side effects.

Clinical presentation and extent of resection impacts progression-free survival in spinal ependymomas.

PURPOSE: Primary treatment of spinal ependymomas involves surgical resection, however recurrence ranges between 50 and 70%. While the association of survival outcomes with lesion extent of resection (EOR) has been studied, existing analyses are limited by small samples and archaic data resulting in an inhomogeneous population. We investigated the relationship between EOR and survival outcomes, chiefly overall survival (OS) and progression-free survival (PFS), in a large contemporary cohort of spinal ependymoma patients. METHODS: Adult patients diagnosed with a spinal ependymoma from 2006 to 2021 were identified from an institutional registry. Patients undergoing primary surgical resection at our institution, ≥ 1 routine follow-up MRI, and pathologic diagnosis of ependymoma were included. Records were reviewed for demographic information, EOR, lesion characteristics, and pre-/post-operative neurologic symptoms. EOR was divided into 2 classifications: gross total resection (GTR) and subtotal resection (STR). Log-rank test was used to compare OS and PFS between patient groups. RESULTS: Sixty-nine patients satisfied inclusion criteria, with 79.7% benefitting from GTR. The population was 56.2% male with average age of 45.7 years, and median follow-up duration of 58 months. Cox multivariate model demonstrated significant improvement in PFS when a GTR was attained (p <.001). Independently ambulatory patients prior to surgery had superior PFS (p <.001) and OS (p =.05). In univariate analyses, patients with a syrinx had improved PFS (p =.03) and were more likely to benefit from GTR (p =.01). Alternatively, OS was not affected by EOR (p =.78). CONCLUSIONS: In this large, contemporary series of adult spinal ependymoma patients, we demonstrated improvements in PFS when GTR was achieved.

Executive summary of the American Radium Society appropriate use criteria for brain metastases in epidermal growth factor receptor mutated-mutated and ALK-fusion non-small cell lung cancer.

The American Radium Society (ARS) Central Nervous System (CNS) committee reviewed literature on epidermal growth factor receptor mutated (EGFRm) and ALK-fusion (ALK+) tyrosine kinase inhibitors (TKIs) for the treatment of brain metastases (BrMs) from non-small cell lung cancers (NSCLC) to generate appropriate use guidelines addressing use of TKIs in conjunction with or in lieu of radiotherapy (RT). The panel developed three key questions to guide systematic review: can radiotherapy be deferred in patients receiving EGFR or ALK TKIs at (1) diagnosis or (2) recurrence? Should TKI be administered concurrently with RT (3)? Two literature searches were performed (May 2019 and December 2023). The panel developed 8 model cases and voted on treatment options using a 9-point scale, with 1-3, 4-6 and 7-9 corresponding to usually not appropriate, may be appropriate, and usually appropriate (respectively), per the UCLA/RAND Appropriateness Method. Consensus was achieved in only 4 treatment scenarios, all consistent with existing ARS-AUC guidelines for multiple BrM. The panel did not reach consensus that RT can be appropriately deferred in patients with BrM receiving CNS penetrant ALK or EGFR TKIs, though median scores indicated deferral may be appropriate under most circumstances. Whole brain RT with concurrent TKI generated broad disagreement except in cases with 2-4 BrM, where it was considered usually not appropriate. We identified no definitive studies dictating optimal sequencing of TKIs and RT for EGFRm and ALK+ BrM. Until such studies are completed, the committee hopes these cases guide decision- making in this complex clinical space.

Using standardized workflows and quantitative data-driven management to reduce time interval from simulation to treatment initiation.

PURPOSE: External beam radiotherapy is a complex process, involving timely coordination among multiple teams. The aim of this study is to report our experience of establishing a standardized workflow and using quantitative data and metrics to manage the time-to-treatment initiation (TTI). METHODS AND MATERIALS: Starting in 2014, we established a standard process in a radiation oncology-specific electronic medical record system (RO-EMR) for patients receiving external beam radiation therapy in our department, aiming to measure the time interval from simulation to treatment initiation, defined as TTI, for radiation oncology. TTI data were stratified according to the following treatment techniques: three-dimensional (3D) conformal therapy, intensity-modulated radiotherapy (IMRT), and stereotactic body radiotherapy (SBRT). Statistical analysis was performed with the Mann-Whitney test for the respective metrics of aggregate data for the initial period 2012- 2015 (PI) and the later period 2016-2019 (PII). RESULT: Over 8 years, the average annual number of treatments for PI and PII were 1760 and 2357 respectively, with 3D, IMRT, and SBRT treatments accounting for 53, 29, 18% and 44, 34, 22%, respectively, of the treatment techniques. The median TTI for 3D, IMRT, and SBRT for PI and PII were 1, 6, 7, and 1, 5, 7 days, respectively, while the 90th percentile TTI for the three techniques in both periods were 5, 9, 11 and 4, 9, 10 days, respectively. From the aggregate data, the TTI was significantly reduced (p = 0.0004, p < 0.0001, p < 0.0001) from PI to PII for the three treatment techniques. CONCLUSION: Establishing a standardized workflow and frequently measuring TTI resulted in shortening the TTI during the early years (in PI) and maintaining the established TTI in the subsequent years (in PII).

Stereotactic Radiosurgery in the Management of Brain Metastases: A Case-Based Radiosurgery Society Practice Guideline.

Purpose: Brain metastases are common among adult patients with solid malignancies and are increasingly being treated with stereotactic radiosurgery (SRS). As more patients with brain metastases are becoming eligible for SRS, there is a need for practical review of patient selection and treatment considerations. Methods and Materials: Two patient cases were identified to use as the foundation for a discussion of a wide and representative range of management principles: (A) SRS alone for 5 to 15 lesions and (B) a large single metastasis to be treated with pre- or postoperative SRS. Patient selection, fractionation, prescription dose, treatment technique, and dose constraints are discussed. Literature relevant to these cases is summarized to provide a framework for treatment of similar patients. Results: Treatment of brain metastases with SRS requires many considerations including optimal patient selection, fractionation selection, and plan optimization. Conclusions: Case-based practice guidelines developed by the Radiosurgery Society provide a practical guide to the common scenarios noted above affecting patients with metastatic brain tumors.

ACR-ARS Practice Parameter for Radiation Oncology.

BACKGROUND: This practice parameter was revised collaboratively by the American College of Radiology (ACR), and the American Radium Society. This practice parameter provides updated reference literature regarding radiation oncology practice and its key personnel. METHODS: This practice parameter was developed according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website ( https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards ) by the Committee on Practice Parameters-Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with the American Radium Society. RESULTS: This practice parameter provides a comprehensive update to the reference literature regarding radiation oncology practice in general. The overall roles of the radiation oncologist, the Qualified Medical Physicist, and other specialized personnel involved in the delivery of external-beam radiation therapy are discussed. The use of radiation therapy requires detailed attention to equipment, patient and personnel safety, equipment maintenance and quality assurance, and continuing staff education. Because the practice of radiation oncology occurs in a variety of clinical environments, the judgment of a qualified radiation oncologist should be used to apply these practice parameters to individual practices. Radiation oncologists should follow the guiding principle of limiting radiation exposure to patients and personnel while accomplishing therapeutic goals. CONCLUSION: This practice parameter can be used as an effective tool to guide radiation oncology practice by successfully incorporating the close interaction and coordination among radiation oncologists, medical physicists, dosimetrists, nurses, and radiation therapists.