Radiosurgery Society Case-Based Guide to Stereotactic Body Radiation Therapy for Challenging Cases of Spinal Metastases.

PURPOSE: Spinal stereotactic body radiation therapy (SBRT) has become the standard of care in management of patients with limited sites of metastatic disease, radio-resistant 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. MATERIALS AND METHODS: 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 utilizing 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.

Is pulsed saturation transfer sufficient for differentiating radiation necrosis from tumor progression in brain metastases?

Background: Stereotactic radiosurgery (SRS) for the treatment of brain metastases delivers a high dose of radiation with excellent local control but comes with the risk of radiation necrosis (RN), which can be difficult to distinguish from tumor progression (TP). Magnetization transfer (MT) and chemical exchange saturation transfer (CEST) are promising techniques for distinguishing RN from TP in brain metastases. Previous studies used a 2D continuous-wave (ie, block radiofrequency [RF] saturation) MT/CEST approach. The purpose of this study is to investigate a 3D pulsed saturation MT/CEST approach with perfusion MRI for distinguishing RN from TP in brain metastases. Methods: The study included 73 patients scanned with MT/CEST MRI previously treated with SRS or fractionated SRS who developed enhancing lesions with uncertain diagnoses of RN or TP. Perfusion MRI was acquired in 49 of 73 patients. Clinical outcomes were determined by at least 6 months of follow-up or via pathologic confirmation (in 20% of the lesions). Results: Univariable logistic regression resulted in significant variables of the quantitative MT parameter 1/(RA·T2A), with 5.9 ±â€…2.7 for RN and 6.5 ±â€…2.9 for TP. The highest AUC of 75% was obtained using a multivariable logistic regression model for MT/CEST parameters, which included the CEST parameters of AREXAmide,0.625µT (P = .013), AREXNOE,0.625µT (P = .008), 1/(RA·T2A) (P = .004), and T1 (P = .004). The perfusion rCBV parameter did not reach significance. Conclusions: Pulsed saturation transfer was sufficient for achieving a multivariable AUC of 75% for differentiating between RN and TP in brain metastases, but had lower AUCs compared to previous studies that used a block RF approach.

Gadolinium Enhanced T2 FLAIR is an Imaging Biomarker of Radiation Necrosis and Tumor Progression in Patients with Brain Metastases.

BACKGROUND AND PURPOSE: Differentiating radiation necrosis (RN) from tumor progression (TP) after radiotherapy for brain metastases is an important clinical problem requiring advanced imaging techniques which may not be widely available and are challenging to perform at multiple time points. The ability to leverage conventional MRI for this problem, could have meaningful clinical impact. The purpose of this study was to explore contrast enhanced T2 FLAIR (T2FLAIRc) as a new imaging biomarker of RN and TP. MATERIALS AND METHODS: This single-institution retrospective study included patients with treated brain metastases undergoing DSC-MRI between January 2021 and June 2023. Reference standard assessment was based on histopathology or serial follow-up including results of DSC-MRI for a minimum of 6 months from the first DSC-MRI. The index test was implemented as part of the institutional brain tumor MRI protocol and preceded the first DSC-MRI. T2FLAIRc and gadolinium enhanced T1 MPRAGE (T1c) signal were normalized against normal brain parenchyma and expressed as z-score. Mean signal intensity of enhancing disease for RN and TP groups were compared using unpaired t-test. Receiver operator characteristic (ROC) curves and area under the ROC curve (AUC) were derived by bootstrapping. DeLong test was used to compare AUC. RESULTS: 56 participants (mean age, 62 years +/-12.7 [SD]; 39 females); 28 RN, 28 TP were evaluated. The index MRI was performed on average 73 days +/-34 [SD] before the first DSC-MRI. Significantly higher z-scores were found for RN using T2FLAIRc (8.3 versus 5.8, p<0.001) and T1c (4.1 versus 3.5, p=0.02). AUC for T2FLAIRc (0.83, 95% CI, 0.72-0.92) was greater than T1c (0.70, 95% CI, 0.560.83) (p = 0.04). The AUC of DSC derived rCBV (0.82, 95% CI, 0.70-0.93) was not significantly different from T2FLAIRc (p = 0.9). CONCLUSIONS: A higher normalized T1c and T2FLAIRc signal intensity was found for RN. In a univariable test, mean T2FLAIRc signal intensity of enhancing voxels showed good discrimination performance for distinguishing RN from TP. The results of this work demonstrate the potential of T2FLAIRc as an imaging biomarker in the work-up of RN in patients with brain metastases. ABBREVIATIONS: AUC = area under the receiver operating characteristic curve; RN = radiation necrosis; ROC = receiver operating characteristic; SRS = stereotactic radiosurgery; T1c = contrast enhanced T1; T2FLAIRc = contrast enhanced T2 FLAIR; TP = tumor progression.

Streamlining the Journey of Research Into Clinical Practice: Making Your Patients and Practice Flourish Understanding and Setting Treatment Expectations for Patients With Metastatic Spine Tumors.

STUDY DESIGN: Literature review with clinical recommendation. OBJECTIVE: A concise curation of the latest spine literature exploring the relationship between expectations and satisfaction for patients with metastatic spinal disease (MSD). Deliver recommendations to practicing clinicians regarding interpretation and utilisation of this evidence. METHODS: The latest spine literature in the topic of factors affecting the expectations of patients with MSD was reviewed and clinical recommendations were formulated. Recommendations are graded as strong or Conditional. RESULTS: 5 articles were selected. Article 1: risk factors for the development of dissatisfaction from a cohort of 362 MSD patients. Strong recommendation to incorporate risk factor assessment when considering treatment. Article 2: systematic review assessing the relationship between pre-operative patient expectations and subsequent satisfaction in allied disciplines. Conditional recommendation to optimize patient expectation to positively modify patient satisfaction. Article 3: qualitative study of how clinicians, from different specialties, counsel patients with MSD pre-treatment. Strong recommendation to use a multidisciplinary approach. Article 4 qualitative study of how MSD patients experience their pre-treatment counselling and how that affected their appreciation of treatment success. Conditional recommendation to furnish patients with tailored, expected outcomes in the context of systemic progression. Article 5 Design and validation of a pre-treatment questionnaire specific to MSD. A conditional recommendation to incorporate this questionnaire in clinical and research MSD practice. CONCLUSION: Patients with MSD are approaching end of life care and high levels of treatment satisfaction are crucial at this juncture. The role of expectation management and comprehensive counselling is critical.

Protocol for a systematic review with prospective individual patient data meta-analysis in EGFR-mutant NSCLC with brain metastases to assess the effect of SRS+osimertinib compared to osimertinib alone: the STARLET Collaboration.

BACKGROUND: Patients with advanced non-small-cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor (EGFR) gene are a heterogeneous population who often develop brain metastases (BM). The optimal management of patients with asymptomatic brain metastases is unclear given the activity of newer-generation targeted therapies in the central nervous system. We present a protocol for an individual patient data (IPD) prospective meta-analysis to evaluate whether the addition of stereotactic radiosurgery (SRS) before osimertinib treatment will lead to better control of intracranial metastatic disease. This is a clinically relevant question that will inform practice. METHODS: Randomised controlled trials will be eligible if they include participants with BM arising from EGFR-mutant NSCLC and suitable to receive osimertinib both in the first-line and second-line settings (P); comparisons of SRS followed by osimertinib versus osimertinib alone (I, C) and intracranial disease control included as an endpoint (O). Systematic searches of Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (EBSCO), PsychInfo, ClinicalTrials.gov and the WHO's International Clinical Trials Registry Platform's Search Portal will be undertaken. An IPD meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome is intracranial progression-free survival, as determined by response assessment in neuro-oncology-BM criteria. Secondary outcomes include overall survival, time to whole brain radiotherapy, quality of life, and adverse events of special interest. Effect differences will be explored among prespecified subgroups. ETHICS AND DISSEMINATION: Approved by each trial's ethics committee. Results will be relevant to clinicians, researchers, policymakers and patients, and will be disseminated via publications, presentations and media releases. PROSPERO REGISTRATION: CRD42022330532.

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.

Stereotactic Radiosurgery for Intermediate (III) or High (IV-V) Spetzler-Martin Grade Arteriovenous Malformations: International Stereotactic Radiosurgery Society Practice Guideline.

BACKGROUND AND OBJECTIVES: Consensus guidelines do not exist to guide the role of stereotactic radiosurgery (SRS) in the management of patients with Spetzler-Martin Grade III-V arteriovenous malformations (AVMs). We sought to establish SRS practice guidelines for Grade III-V AVMs based on a critical systematic review of the published literature. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant search of Medline, Embase, and Scopus, 1986 to 2023, for publications reporting post-SRS outcomes in ≥10 Grade III-V AVMs with the median follow-up ≥24 months was performed. Primary end points were AVM obliteration and post-SRS hemorrhage. Secondary end points included dosimetric variables, Spetzler-Martin parameters, and neurological outcome. RESULTS: : In total, 2463 abstracts were screened, 196 manuscripts were reviewed, and 9 met the strict inclusion criteria. The overall sample of 1634 AVMs consisted of 1431 Grade III (88%), 186 Grade IV (11%), and 11 Grade V lesions (1%). Total median post-SRS follow-up was 53 months for Grade III and 43 months for Grade IV-V AVMs (ranges, 2-290; 12-262). For Grade III AVMs, the crude obliteration rate was 72%, and among Grade IV-V lesions, the crude obliteration rate was 46%. Post-SRS hemorrhage was observed in 7% of Grade III compared with 17% of Grade IV-V lesions. Major permanent deficits or death from hemorrhage or radiation-induced complications occurred in 86 Grade III (6%) and 22 Grade IV-V AVMs (12%). CONCLUSION: Most patients with Spetzler-Martin Grade III AVMs have favorable SRS treatment outcomes; however, the obliteration rate for Grade IV-V AVMs is less than 50%. The available studies are heterogenous and lack nuanced, long-term, grade-specific outcomes.

Repeat Single-Session Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations: A Systematic Review, Meta-Analysis, and International Stereotactic Radiosurgery Society Practice Guidelines.

BACKGROUND AND OBJECTIVES: Repeat stereotactic radiosurgery (SRS) for residual arteriovenous malformations (AVMs) can be considered as a salvage approach after failure of initial SRS. There are no published guidelines regarding patient selection, timing, or SRS parameters to guide clinical practice. This systematic review aimed to review outcomes and complications from the published literature to inform practice recommendations provided on behalf of the International Stereotactic Radiosurgery Society. METHODS: We performed a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search of MEDLINE, Scopus, Web of Science, and Embase was conducted. Fourteen studies with 925 patients met the inclusion criteria. Patients were treated between 1985 and 2022. All studies were retrospective, except for one prospective cohort. RESULTS: The median patient age at repeat SRS ranged from 32 to 60 years. Four studies (630 patients) reported detailed information on Spetzler-Martin grade at the time of repeat SRS; 12.54% of patients had Spetzler-Martin grade I AVMs (79/630 patients), 46.51% had grade II (293/630), 34.92% had grade III (220/630), 5.08% had grade IV (32/630), and 0.95% had grade V (6/630). The median prescription doses varied between 15 and 25 Gy (mean, 13.06-22.8 Gy). The pooled overall obliteration rate at the last follow-up after repeat SRS was 59% (95% CI 51%-67%) with a median follow-up between 21 and 50 months. The pooled hemorrhage incidence at the last follow-up was 5% (95% CI 4%-7%), and the pooled overall radiation-induced change incidence was 12% (95% CI 7%-20%). CONCLUSION: For an incompletely obliterated AVM, repeat radiosurgery after 3 to 5 years of follow-up from the first SRS provides a reasonable benefit to the risk profile. After repeat SRS, obliteration is achieved in the majority of patients. The risk of hemorrhage or radiation-induced change appears low, and International Stereotactic Radiosurgery Society recommendations are presented.

Patient-Reported and Clinical Outcomes of Surgically Treated Patients With Symptomatic Spinal Metastases: Results From Epidemiology, Process, and Outcomes of Spine Oncology (EPOSO), a Prospective, Multi-Institutional and International Study.

BACKGROUND AND OBJECTIVES: The palliative impact of spine surgery for metastatic disease is evolving with improvements in surgical technique and multidisciplinary cancer care. The goal of this study was to prospectively evaluate long-term clinical outcomes including health-related quality-of-life (HRQOL) measures, using spine cancer-specific patient-reported-outcome (PRO) measures, in patients with symptomatic spinal metastases who underwent surgical management. METHODS: The Epidemiology, Process, and Outcomes of Spine Oncology (EPOSO, ClinicalTrials.gov identifier: NCT01825161) trial is a prospective-observational cohort study that included 10 specialist centers in North America and Europe. Patients aged 18 to 75 years who underwent surgery for spinal metastases were included. Prospective assessments included both spine tumor-specific and generic PRO tools which were collected for a minimum of 2 years post-treatment or until death. RESULTS: Two hundred and eighty patients (51.8% female, mean age 57.9 years) were included. At presentation, the mean Charlson Comorbidity Index was 6.0, 35.7% had neurological deficits as defined by the American Spinal Cord Injury Association scores, 47.2% had high-grade epidural spinal cord compression (2-3), and 89.6% had impending or frank instability as measured by a Spinal Instability Neoplastic Score of ≥7. The most common primary tumor sites were breast (20.2%), lung (18.8%), kidney (16.2%), and prostate (6.5%). The median overall survival postsurgery was 501 days, and the 2-year progression-free-survival rate was 38.4%. Compared with baseline, significant and durable improvements in HRQOL were observed at the 6-week, 12-week, 26-week, 1-year, and 2-year follow-up assessments from a battery of PRO questionnaires including the spine cancer-specific, validated, Spine Oncology Study Group Outcomes Questionnaire v2.0, the Short Form 36 version 2, EuroQol-5 Dimension (3L), and pain numerical rating scale score. CONCLUSION: Multi-institutional, prospective-outcomes data confirm that surgical decompression and/or stabilization provides meaningful and durable improvements in multiple HRQOL domains, including spine-specific outcomes based on the Spine Oncology Study Group Outcomes Questionnaire v2.0, for patients with metastatic spine disease.

Safety and Tolerability of Online Adaptive High-Field Magnetic Resonance-Guided Radiotherapy.

Importance: In 2018, the first online adaptive magnetic resonance (MR)-guided radiotherapy (MRgRT) system using a 1.5-T MR-equipped linear accelerator (1.5-T MR-Linac) was clinically introduced. This system enables online adaptive radiotherapy, in which the radiation plan is adapted to size and shape changes of targets at each treatment session based on daily MR-visualized anatomy. Objective: To evaluate safety, tolerability, and technical feasibility of treatment with a 1.5-T MR-Linac, specifically focusing on the subset of patients treated with an online adaptive strategy (ie, the adapt-to-shape [ATS] approach). Design, Setting, and Participants: This cohort study included adults with solid tumors treated with a 1.5-T MR-Linac enrolled in Multi Outcome Evaluation for Radiation Therapy Using the MR-Linac (MOMENTUM), a large prospective international study of MRgRT between February 2019 and October 2021. Included were adults with solid tumors treated with a 1.5-T MR-Linac. Data were collected in Canada, Denmark, The Netherlands, United Kingdom, and the US. Data were analyzed in August 2023. Exposure: All patients underwent MRgRT using a 1.5-T MR-Linac. Radiation prescriptions were consistent with institutional standards of care. Main Outcomes and Measures: Patterns of care, tolerability, and technical feasibility (ie, treatment completed as planned). Acute high-grade radiotherapy-related toxic effects (ie, grade 3 or higher toxic effects according to Common Terminology Criteria for Adverse Events version 5.0) occurring within the first 3 months after treatment delivery. Results: In total, 1793 treatment courses (1772 patients) were included (median patient age, 69 years [range, 22-91 years]; 1384 male [77.2%]). Among 41 different treatment sites, common sites were prostate (745 [41.6%]), metastatic lymph nodes (233 [13.0%]), and brain (189 [10.5%]). ATS was used in 1050 courses (58.6%). MRgRT was completed as planned in 1720 treatment courses (95.9%). Patient withdrawal caused 5 patients (0.3%) to discontinue treatment. The incidence of radiotherapy-related grade 3 toxic effects was 1.4% (95% CI, 0.9%-2.0%) in the entire cohort and 0.4% (95% CI, 0.1%-1.0%) in the subset of patients treated with ATS. There were no radiotherapy-related grade 4 or 5 toxic effects. Conclusions and Relevance: In this cohort study of patients treated on a 1.5-T MR-Linac, radiotherapy was safe and well tolerated. Online adaptation of the radiation plan at each treatment session to account for anatomic variations was associated with a low risk of acute grade 3 toxic effects.

Contemporary trends in the incidence and timing of spinal metastases: A population-based study.

Background: Spinal metastases are a significant complication of advanced cancer. In this study, we assess temporal trends in the incidence and timing of spinal metastases and examine underlying patient demographics and primary cancer associations. Methods: In this population-based retrospective cohort study, health data from 2007 to 2019 in Ontario, Canada were analyzed (n = 37, 375 patients identified with spine metastases). Primary outcomes were annual incidence of spinal metastasis, and time to metastasis after primary diagnosis. Results: The age-standardized incidence of spinal metastases increased from 229 to 302 cases per million over the 13-year study period. The average annual percent change (AAPC) in incidence was 2.2% (95% CI: 1.4% to 3.0%) with patients aged ≥85 years demonstrating the largest increase (AAPC 5.2%; 95% CI: 2.3% to 8.3%). Lung cancer had the greatest annual incidence, while prostate cancer had the greatest increase in annual incidence (AAPC 6.5; 95% CI: 4.1% to 9.0%). Lung cancer patients were found to have the highest risk of spine metastasis with 10.3% (95% CI: 10.1% to 10.5%) of patients being diagnosed at 10 years. Gastrointestinal cancer patients were found to have the lowest risk of spine metastasis with 1.0% (95% CI: 0.9% to 1.0%) of patients being diagnosed at 10 years. Conclusions: The incidence of spinal metastases has increased in recent years, particularly among older patients. The incidence and timing vary substantially among different primary cancer types. These findings contribute to the understanding of disease trends and emphasize a growing population of patients who require subspecialty care.

Predictors of Tumor Dynamics Over a 6-Week Course of Concurrent Chemoradiotherapy for Glioblastoma and the Effect on Survival.

PURPOSE: We present the final analyses of tumor dynamics and their prognostic significance during a 6-week course of concurrent chemoradiotherapy for glioblastoma in the Glioblastoma Longitudinal Imaging Observational study. METHODS AND MATERIALS: This is a prospective serial magnetic resonance imaging study in 129 patients with glioblastoma who had magnetic resonance imaging obtained at radiation therapy (RT) planning (F0), fraction 10 (F10), fraction 20 (F20), and 1-month post-RT. Tumor dynamics assessed included gross tumor volume relative to F0 (Vrel) and tumor migration distance (dmigration). Covariables evaluated included: corpus callosum involvement, extent of surgery, O6-methylguanine-DNA-methyltransferase methylation, and isocitrate dehydrogenase mutation status. RESULTS: The median Vrel were 0.85 (range, 0.25-2.29) at F10, 0.79 (range, 0.09-2.22) at F20, and 0.78 (range, 0.13-4.27) at 1 month after completion of RT. The median dmigration were 4.7 mm (range, 1.1-20.4 mm) at F10, 4.7 mm (range, 0.8-20.7 mm) at F20, and 6.1 mm (range, 0.0-45.5 mm) at 1 month after completion of RT. Compared with patients who had corpus callosum involvement (n = 26), those without corpus callosum involvement (n = 103) had significant Vrel reduction at F20 (P = .03) and smaller dmigration at F20 (P = .007). Compared with patients who had biopsy alone (n = 19) and subtotal resection (n = 71), those who had gross total resection (n = 38) had significant Vrel reduction at F10 (P = .001) and F20 (P = .001) and a smaller dmigration at F10 (P = .03) and F20 (P = .002). O6-Methylguanine-DNA-methyltransferase methylation and isocitrate dehydrogenase mutation status were not significantly associated with tumor dynamics. The median progression-free survival and overall survival (OS) were 8.5 months (95% CI, 6.9-9.9) and 20.4 months (95% CI, 17.6-25.2). In multivariable analyses, patients with Vrel ≥ 1.33 at F10 had worse OS (hazard ratio [HR], 4.6; 95% CI, 1.8-11.4; P = .001), and patients with dmigration ≥ 5 mm at 1-month post-RT had worse progression-free survival (HR, 1.76; 95% CI, 1.08-2.87) and OS (HR, 2.2; 95% CI, 1.2-4.0; P = .007). CONCLUSIONS: Corpus callosum involvement and extent of surgery are independent predictors of tumor dynamics during RT and can enable patient selection for adaptive RT strategies. Significant tumor enlargement at F10 and tumor migration 1-month post-RT were associated with poorer OS.

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.

Evolving concepts in margin strategies and adaptive radiotherapy for glioblastoma: A new future is on the horizon.

Chemoradiotherapy is the standard treatment after maximal safe resection for glioblastoma (GBM). Despite advances in molecular profiling, surgical techniques, and neuro-imaging, there have been no major breakthroughs in radiotherapy (RT) volumes in decades. Although the majority of recurrences occur within the original gross tumor volume (GTV), treatment of a clinical target volume (CTV) ranging from 1.5 to 3.0 cm beyond the GTV remains the standard of care. Over the past 15 years, the incorporation of standard and functional MRI sequences into the treatment workflow has become a routine practice with increasing adoption of MR simulators, and new integrated MR-Linac technologies allowing for daily pre-, intra- and post-treatment MR imaging. There is now unprecedented ability to understand the tumor dynamics and biology of GBM during RT, and safe CTV margin reduction is being investigated with the goal of improving the therapeutic ratio. The purpose of this review is to discuss margin strategies and the potential for adaptive RT for GBM, with a focus on the challenges and opportunities associated with both online and offline adaptive workflows. Lastly, opportunities to biologically guide adaptive RT using non-invasive imaging biomarkers and the potential to define appropriate volumes for dose modification will be discussed.

Utility of molecular markers in predicting local control specific to lung cancer spine metastases treated with stereotactic body radiotherapy.

BACKGROUND AND PURPOSE: We report outcomes following spine stereotactic body radiotherapy (SBRT) in metastatic non-small cell lung cancer (NSCLC) and the significance of programmed death-ligand 1 (PD-L1) status, epidermal growth factor receptor (EGFR) mutation and timing of immune check point inhibitors (ICI) on local failure (LF). MATERIALS AND METHODS: 165 patients and 389 spinal segments were retrospectively reviewed from 2009 to 2021. Baseline patient characteristics, treatment and outcomes were abstracted. Primary endpoint was LF and secondary, overall survival (OS) and vertebral compression fracture (VCF). Multivariable analysis (MVA) evaluated factors predictive of LF and VCF. RESULTS: The median follow-up and OS were: 13.0 months (range, 0.5-95.3 months) and 18.4 months (95% CI 11.4-24.6). 52.1% were male and 76.4% had adenocarcinoma. Of the 389 segments, 30.3% harboured an EGFR mutation and 17.0% were PD-L1 ≥ 50%. The 24 months LF rate in PD-L1 ≥ 50% vs PD-L1 < 50% was 10.7% vs. 38.0%, and in EGFR-positive vs. negative was 18.1% vs. 30.0%. On MVA, PD-L1 status of ≥ 50% (HR 0.32, 95% CI 0.15-0.69, p = 0.004) significantly predicted for lower LF compared to PD-L1 < 50%. Lower LF trend was seen with ICI administration peri and post SBRT (HR 0.41, 95% CI 0.16-1.05, p = 0.062). On MVA, polymetastatic disease (HR 3.28, 95% CI 1.84-5.85, p < 0.0001) and ECOG ≥ 2 (HR 1.87, 95% CI 1.16-3.02, p = 0.011) significantly predicted for worse OS and absence of baseline VCF predicted for lower VCF rate (HR 0.20, 95% CI 0.10-0.39, p < 0.0001). CONCLUSION: We report a significant association of PD-L1 ≥ 50% status on improved LC rates from spine SBRT in NSCLC patients.

Human Epidermal Growth Factor Receptor 2-Low Breast Cancer Brain Metastases: An Opportunity for Targeted Systemic Therapies in a High-Need Patient Population.

PURPOSE: Trastuzumab deruxtecan is a new treatment option for patients with advanced human epidermal growth factor receptor 2 (HER2)-low breast cancer (BC). Although HER2-low status has been characterized in early and advanced BC, it has yet to be fully characterized in brain metastases (BrM). METHODS: Patients who underwent surgery for BC BrM at Sunnybrook Health Sciences Centre and for whom HER2 status was available on resected BrM were studied. Estrogen receptor, progesterone receptor, and HER2 status were assessed on the basis of ASCO/College of American Pathologists (CAP) guidelines. HER2-zero was defined as immunohistochemistry (IHC) 0; HER2-low was defined as IHC 1+ or IHC 2+ with fluorescence in situ hybridization (FISH)-negative status. HER2-positive (HER2+) was defined as IHC 3+ or IHC 2+ with positive FISH. Clinicopathologic features were recorded. We also assessed the prognostic association between extent of HER2 expression and (1) brain-specific progression-free survival (bsPFS), as well as (2) overall survival (OS). RESULTS: In this retrospective cohort of 102 patients with resected BC BrM, 53% (n = 54) were HER2+, 29.4% (n = 30) were HER2-low, and 17.6% (n = 18) had HER2-zero status. Among BrM that were triple-negative on the basis of ASCO/CAP guidelines, 63.6% (n = 14/22) were reclassified as being HER2-low. Sixty percent (n = 15/25) of BrM that were hormone receptor-positive/HER2-negative (HR+/HER2-) were reclassified as being HER2-low. In total, 51 patients had matched primary breast and BrM tissue available; results of HER2 status when categorized as HER2-zero, HER2-low, and HER2+ were concordant in 82.3% (n = 42/51) of cases (Cohen's kappa, 0.58; P = .07). There was no significant association between HER2-zero, HER2-low, and HER2+ status in BrM and either bsPFS or OS. CONCLUSION: Among patients with surgically resected BrM, a high proportion of those with metastatic triple-negative BC and HR+/HER2- disease have HER2-low BrM with potential to benefit from HER2-targeted therapy.

Stereotactic body radiation therapy for spinal metastases: A new standard of care.

Advancements in systemic therapies for patients with metastatic cancer have improved overall survival and, hence, the number of patients living with spinal metastases. As a result, the need for more versatile and personalized treatments for spinal metastases to optimize long-term pain and local control has become increasingly important. Stereotactic body radiation therapy (SBRT) has been developed to meet this need by providing precise and conformal delivery of ablative high-dose-per-fraction radiation in few fractions while minimizing risk of toxicity. Additionally, advances in minimally invasive surgical techniques have also greatly improved care for patients with epidural disease and/or unstable spines, which may then be combined with SBRT for durable local control. In this review, we highlight the indications and controversies of SBRT along with new surgical techniques for the treatment of spinal metastases.