Stereotactic ablative radiotherapy versus conventional fractionated radiotherapy for clinical early-stage non-small-cell lung cancer: a population-based study.

INTRODUCTION: The use of stereotactic ablative radiotherapy (SABR) over conventional fractionated radiotherapy (CFRT) for early-stage non-small-cell lung cancer (NSCLC) has been advocated, but is also debated in the literature. METHODS: In this retrospective cohort study, we adopted a target trial emulation framework to identify eligible patients diagnosed between 2011 and 2021 using the Taiwan Cancer Registry. In the primary analysis, the overall survival (OS) was the primary endpoint, whereas incidences of lung cancer mortality and radiation pulmonary toxicity were the secondary endpoints. Extensive supplementary analyses were also conducted. RESULTS: We included 351 patients in the primary analysis and found that the OS was not significantly different between the SABR (n = 290) and CFRT (n = 61) groups. The propensity score weighting adjusted hazard ratio of death was 0.75 (95% confidence interval 0.53-1.07, p = 0.118). The secondary endpoints and supplementary analyses showed no significant differences. CONCLUSIONS: The OS of patients with early-stage NSCLC treated with SABR was not significantly different from that of patients treated with CFRT alone. The results of the relevant ongoing clinical trials are eagerly awaited.

Stereotactic radiotherapy for liver oligometastases: a pooled analysis following the estro/eortc consensus recommendations.

A large pooled analysis of liver oligometastases, classified accordingly to the ESTRO/EORTC recommendations, treated by stereotactic radiotherapy (SBRT) and Radiosurgery (SRS) was carried out. The clinical and dosimetric data of patients who underwent SBRT/SRS for liver metastases were analysed in terms of efficacy and toxicity profile. In particular, the Local Control (LC), the Distant Metastases Free Survival (DMFS), the Disease-Free Survival (DFS), the Overall Survival (OS), and the Next Systemic Therapy Free Survival (NEST-FS) rates were analysed. 113 patients (M/F: 49/64), accounting for a total of 150 hepatic lesions (March 2006-February 2023) in two Italian radiotherapy Institutions were evaluated. Median age was 67 years old (36-92) and 48 (42.5%) patients had at least one comorbidity. The majority of the lesions were induced (30.7%) or repeated oligoprogressive (12.7%) metastases. 98 lesions were treated with more than one daily fraction (mainly 50 Gy in 5 fractions), while 52 were radiosurgery treatments (mainly 32 Gy). The treatment response at 3-4 months was evaluable in 147 lesions: complete response was 32.0%, partial response 17.0%, and stable disease 32.0%. Actuarial LC, DMFS, DFS, OS, and NEST-FS at 1 year were 75.8%, 37.7%, 34.9%, 78.7%, and 59.4% respectively; while actuarial LC, DMFS, DFS, OS, and NEST-FS at 2 years were 52.1%, 24.9%, 21.9%, 51.3%, and 36.8%, respectively. The achievement of complete response, synchronous oligometastases, and no treatment interruptions correlated with a more favorable outcomes. As per the toxicity profile, we registered only two acute and one late toxicity cases higher than grade 2. Stereotactic treatment for liver metastases seems to be a safe and promising option in terms of local control. The best results in term of outcomes have been obtained in patients with complete response, synchronous oligometastases, favorable histology, and no treatment interruptions.

Dosimetric comparison of IMPT vs VMAT for multiple lung lesions: an NTCP model-based decision-making strategy.

To compare the dosimetric differences in volumetric modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT) in stereotactic body radiation therapy (SBRT) of multiple lung lesions and determine a normal tissue complication probability (NTCP) model-based decision strategy that determines which treatment modality the patient will use. A total of 41 patients were retrospectively selected for this study. The number of patients with 1-6 lesions was 5, 16, 7, 6, 3, and 4, respectively. A prescription dose of 70 GyRBE in 10 fractions was given to each lesion. SBRT plans were generated using VMAT and IMPT. All the IMPT plans used robustness optimization with ± 3.5% range uncertainties and 5 mm setup uncertainties. Dosimetric metrics and the predicted NTCP value of radiation pneumonitis (RP), esophagitis, and pericarditis were analyzed to evaluate the potential clinical benefits between different planning groups. In addition, a threshold for the ratio of PTV to lungs (%) to determine whether a patient would benefit highly from IMPT was determined using receiver operating characteristic curves. All plans reached target coverage (V70GyRBE ≥ 95%). Compared with VMAT, IMPT resulted in a significantly lower dose of most thoracic normal tissues. For the 1-2, 3-4 and 5-6 lesion groups, the lung V5 was 29.90 ± 9.44%, 58.33 ± 13.35%, and 81.02 ± 5.91% for VMAT and 11.34 ± 3.11% (p < 0.001), 21.45 ± 3.80% (p < 0.001), and 32.48 ± 4.90% (p < 0.001) for IMPT, respectively. The lung V20 was 12.07 ± 4.94%, 25.57 ± 6.54%, and 43.99 ± 11.83% for VMAT and 6.76 ± 1.80% (p < 0.001), 13.14 ± 2.27% (p < 0.01), and 19.62 ± 3.48% (p < 0.01) for IMPT. The Dmean of the total lung was 7.65 ± 2.47 GyRBE, 14.78 ± 2.75 GyRBE, and 21.64 ± 4.07 GyRBE for VMAT and 3.69 ± 1.04 GyRBE (p < 0.001), 7.13 ± 1.41 GyRBE (p < 0.001), and 10.69 ± 1.81 GyRBE (p < 0.001) for IMPT. Additionally, in the VMAT group, the maximum NTCP value of radiation pneumonitis was 73.91%, whereas it was significantly lower in the IMPT group at 10.73%. The accuracy of our NTCP model-based decision model, which combines the number of lesions and PTV/Lungs (%), was 97.6%. The study demonstrated that the IMPT SBRT for multiple lung lesions had satisfactory dosimetry results, even when the number of lesions reached 6. The NTCP model-based decision strategy presented in our study could serve as an effective tool in clinical practice, aiding in the selection of the optimal treatment modality between VMAT and IMPT.

Comparative analysis of upfront stereotactic radiosurgery and watchful waiting in the management of newly diagnosed vestibular schwannomas: a systematic review and meta-analysis.

Vestibular schwannomas (VS) are benign intracranial tumors posing significant management challenges. This study aims to compare the outcomes of stereotactic radiosurgery (SRS) and watchful waiting (WW) in the management of newly diagnosed VS, integrating findings from both retrospective and the pioneering V-REX prospective trial. Adhering to PRISMA guidelines, a systematic review was conducted using MEDLINE, Embase, and Cochrane databases. Studies directly comparing SRS with WW for newly diagnosed VS were included. Primary outcomes focused on hearing preservation assessed through the AAO-HNS or Gardner-Robertson hearing classification scales and tumor progression, with secondary outcomes focusing on neurological symptoms, and the need for further treatment. Thirteen studies encompassing 1,635 patients (WW: 891; SRS: 744) were included.While no significant difference was found in serviceable hearing loss at last follow-up (RR = 1.51, [95%CI: 0.98, 2.32], p = 0.06), significant differences favoring WW were observed in pure tone audiometry (PTA) (MD = -13.51 [95%CI: -22.66, -4.37], p = 0.004) and word recognition score (WRS) (MD = 20.48 [95%CI: 9.72, 31.25], p = 0.0002). Analysis of tumor progression indicated no overall significant difference in risk between SRS and WW (RR = 0.40, [95%CI 0.07, 2.40], p = 0.32), but subgroup analysis suggested a lower risk with SRS in certain contexts. The need for further treatments favored SRS (RR = 0.24, [95%CI: 0.07, 0.74], p = 0.007). No significant differences were found in tinnitus and imbalance between the two groups. This comprehensive analysis suggests no marked difference in functional hearing preservation between SRS and WW in managing VS. However, untreated tumors commonly necessitate additional interventions. These findings highlight the need for individualized treatment decisions and underscore the importance of continued monitoring. The study advocates for further prospective trials to refine management strategies for VS.

A randomised controlled trial of Standard Of Care versus RadioAblaTion in Early Stage HepatoCellular Carcinoma (SOCRATES HCC).

BACKGROUND: Therapeutic options for early-stage hepatocellular carcinoma (HCC) in individual patients can be limited by tumor and location, liver dysfunction and comorbidities. Many patients with early-stage HCC do not receive curative-intent therapies. Stereotactic ablative body radiotherapy (SABR) has emerged as an effective, non-invasive HCC treatment option, however, randomized evidence for SABR in the first line setting is lacking. METHODS: Trans-Tasman Radiation Oncology Group (TROG) 21.07 SOCRATES-HCC is a phase II, prospective, randomised trial comparing SABR to other current standard of care therapies for patients with a solitary HCC ≤ 8 cm, ineligible for surgical resection or transplantation. The study is divided into 2 cohorts. Cohort 1 will compromise 118 patients with tumors ≤ 3 cm eligible for thermal ablation randomly assigned (1:1 ratio) to thermal ablation or SABR. Cohort 2 will comprise 100 patients with tumors > 3 cm up to 8 cm in size, or tumors ≤ 3 cm ineligible for thermal ablation, randomly assigned (1:1 ratio) to SABR or best other standard of care therapy including transarterial therapies. The primary objective is to determine whether SABR results in superior freedom from local progression (FFLP) at 2 years compared to thermal ablation in cohort 1 and compared to best standard of care therapy in cohort 2. Secondary endpoints include progression free survival, overall survival, adverse events, patient reported outcomes and health economic analyses. DISCUSSION: The SOCRATES-HCC study will provide the first randomized, multicentre evaluation of the efficacy, safety and cost effectiveness of SABR versus other standard of care therapies in the first line treatment of unresectable, early-stage HCC. It is a broad, multicentre collaboration between hepatology, interventional radiology and radiation oncology groups around Australia, coordinated by TROG Cancer Research. TRIAL REGISTRATION: anzctr.org.au, ACTRN12621001444875, registered 21 October 2021.

Results of Stereotactic Body Radiotherapy With CyberKnife-M6 for Primary and Metastatic Lung Cancer.

Background: The aim of the study was to evaluate the efficacy of stereotactic body radiotherapy (SBRT) using the CyberKnife-M6 (CK-M6) with lung optimized treatment (LOT) module in patients with primary lung cancer and lung metastases. Methods: Forty-two lesions from 35 patients were treated between 2019 and 2022. Four-dimensional computed tomography images were obtained when the patients were in a free breathing modality. Tracking modality was selected prospectively according to the visibility of the target. The median prescribed dose was 48 Gy in four fractions (fx) (28 - 55 Gy/1- 7 fx). The median age was 68 years (47 - 82 years), and 43% of cases were adenocarcinoma. The median lesion size was 15 mm (6 - 36 mm). Results: Complete, partial and stable responses were obtained as 26%, 62%, and 9.5% at a median of 2 months (1 - 6 months), and 35.5%, 47.5% and 5% at the 12th month evaluation, respectively. Grade 3 and higher toxicity was not observed in any case. The mean and 2-year overall survival (OS) was 31.5 months and 54%, and the local recurrence-free survival (LRFS) was 29.6 months and 51%, respectively. In univariate analysis, target lesion type, complete response (CR), and higher esophagus maximum dose were favorable factors for OS and LRFS (P < 0.05). The CR at 12th month evaluation remained significant in multivariate analysis in terms of OS (hazard ratio = 8.602, 95% confidence interval: 1.05 - 70.01; P = 0.044). Conclusions: A mean LRFS of 29.6 months and OS of 31.5 months were obtained in patients with primary and metastatic lung cancer. With a median treatment time of 25 min, motion-managed strategy with CK-M6-LOT-based SBRT is an effective, safe, and comfortable treatment method for lung cancer.

A good response to anti-PD-1 monoclonal antibody plus SBRT in a patient with PD-L1-negative recurrent advanced esophageal cancer: a long-term follow-up case report of a possible abscopal effect.

There are limited treatment options for recurrent advanced esophageal squamous cell carcinoma. A good response with a possible abscopal effect was observed in a patient with programmed death-ligand 1 (PD-L1)-negative recurrent advanced esophageal squamous cell carcinoma treated with an anti-PD-1 monoclonal antibody plus stereotactic body radiotherapy (SBRT). A 66-year-old male patient was diagnosed with recurrent advanced esophageal squamous cell carcinoma with multiple lung metastases (13 metastatic nodules in total) four months after completing radical radiotherapy plus concurrent and consolidated chemotherapy, and PD-L1 expression in the primary esophageal tumor was negative. This patient received 25 cycles of camrelizumab (an anti-PD-1 monoclonal antibody) in total plus upfront SBRT for two metastatic nodules, which was administered after the first cycle of camrelizumab. After this combined treatment, for most nontarget nodules, an obvious volume decrease and fuzzy change were observed, including two nodules that completely vanished. At the end of follow-up, the progression-free survival and duration of response of this patient were 34 months and 32 months, respectively. This case report indicated that an anti-PD-1 monoclonal antibody combined with SBRT was a promising therapeutic strategy for recurrent esophageal squamous cell carcinoma even in patients with negative PD-L1 expression.

Letter to Editor: Cystic vestibular schwannoma - a subgroup analysis from a comparative study between radiosurgery and microsurgery.

This letter evaluates the recent study on the management of cystic vestibular schwannomas (VS) compared to solid VS, focusing on the clinical outcomes of surgery (SURGERY) and radiosurgery (SRS). The study offers significant insights into the differences between these tumor types, emphasizing the challenges posed by cystic VS, including rapid growth, enhanced peritumoral adhesion, and worse post-operative facial nerve outcomes. Notably, cystic VS are associated with higher recurrence rates and poorer preoperative status. The study also highlights lower gross total resection (GTR) rates and poorer long-term tumor control in cystic VS. While SRS shows high rates of functional preservation, it is less effective in ensuring recurrence-free survival in cystic VS compared to solid VS, suggesting surgery may be preferable for achieving the best long-term outcomes, particularly when safe maximal resection is possible. However, the study's retrospective design and limited sample size, along with the lack of standardized follow-up protocols, may impact the generalizability of the findings. Future research should focus on prospective, multicenter studies with standardized protocols to develop evidence-based guidelines for managing cystic VS. Innovative techniques, such as advanced imaging and minimally invasive surgical approaches, may further improve diagnostic accuracy and treatment efficacy. This study underscores the complexities of managing cystic VS and the need for tailored treatment strategies.

Acute toxicity and early PSA response after two-fraction stereotactic radiotherapy for localized prostate cancer using peri-rectal spacing - Initial report of the SABR-Dual trial.

PURPOSE: SABR-Dual is a phase III trial with an initial phase-I safety cohort, of two-fraction stereotactic radiotherapy (SABR) with optional MRI-based focal boost, using peri-rectal spacing, for localized prostate cancer. This represents the initial report from the phase-I non-randomized cohort. MATERIALS AND METHODS: Subjects had favorable intermediate risk (FIR) or low risk (LR) prostate adenocarcinoma, and gland volume <80cc. All underwent radiopaque hydrogel spacer and fiducial marker placement prior to simulation (CT and 3-tesla T2 MRI). The clinical target volume included the entire prostate, and in FIR patients, 1-2cm of seminal vesicle (SV). A 2mm expansion was applied for planning target volume (PTV), and a dose of 27 Gy was prescribed to the PTV-prostate, 23 Gy to the PTV-SV, with an optional 30 Gy simultaneous boost (SIB) to an MRI-defined dominant lesion. Primary endpoint was 3-month patient-reported changes in quality of life based on the EPIC-26, IPSS, and SHIM questionnaires. Secondary endpoints were 6-month quality of life, acute toxicity (using CTCAEv5) and early PSA response. RESULTS: Among the 20 patients in the phase-I cohort, 95% had FIR disease, and 50% received an SIB. At median follow-up of 8 months, a 3-month minimally clinically important change occurred in 1/20 (5%), 6/20 (30%), 2/20 (10%), 4/20 (20%), and 5/20 (25%) in urinary incontinence, urinary obstructive, bowel, sexual, and hormonal domains. There was a mean increase of 1±5.4 in IPSS and decrease of 1.8±6.5 in SHIM scores. Rates of grade 2 urinary and bowel toxicity 10% and 0%, respectively, with no grade ≥3 toxicities. Mean PSA decrease at last follow-up was 70.4%±17.7%. CONCLUSION: This generalizable protocol of two-fraction prostate SABR using peri-rectal spacing is a safe approach for ultra-hypofractionated dose-escalation, with minimal acute toxicity. Longer-term outcomes and direct comparison with standard 5-fraction SABR are being studied in the phase-III randomized portion of SABR-Dual.

Optimizing Choice of Skin Surrogates for Surface-Guided Stereotactic Body Radiotherapy of Lung Lesions Using Four-Dimensional Computed Tomography.

Image-guided radiotherapy supported by surface guidance can help to track lower lung lesions' respiratory motion while reducing a patient's exposure to ionizing radiation. However, it is not always clear how the skin's respiratory motion magnitude and its correlation with the lung lesion's respiratory motion vary between different skin regions of interest (ROI). Four-dimensional computed tomography (4DCT) images provide information on both the skin and lung respiratory motion and are routinely acquired for the purpose of treatment planning in our institution. An analysis of 4DCT images for 57 patients treated in our institution has been conducted to provide information on the respiratory motion magnitudes of nine skin ROIs of the torso, a tracking structure (TS) representing a lower lung lobe lesion, as well as the respiratory motion correlations between the nine ROIs and the TS. The effects of gender and the adipose tissue volume and distribution on these correlations and magnitudes have been analyzed. Significant differences between the ROIs in both the respiratory motion magnitudes and their correlations with the TS have been detected. An overall negative correlation between the ROI respiratory magnitudes and the adipose tissue has been detected for ROIs with rib cage support. A weak to moderate negative correlation between the adipose tissue volume and ROI-to-TS respiratory correlations has been detected for upper thorax ROIs. The respiratory magnitudes in regions without rib support tend to be larger for men than for women, but no differences in the ROI-to-TS correlation between sexes have been detected. The described findings should be considered when choosing skin surrogates for lower lung lesion motion management.

Circulating Tumor DNA Predicts Early Recurrence Following Locoregional Therapy for Oligometastatic Colorectal Cancer.

(1) Background: Local therapies offer a potentially curative approach for patients with oligometastatic colorectal cancer (CRC). An evidence-based consensus recommendation for systemic therapy following definitive locoregional therapy is lacking. Tumor-informed circulating tumor DNA (ctDNA) might provide information to help guide management in this setting. (2) Methods: A multi-institutional retrospective study was conducted, including patients with CRC that underwent curative-intent locoregional therapy to an isolated site of metastatic disease, followed by tumor-informed ctDNA assessment. The Kaplan-Meier method and log-rank tests were used to compare disease-free survival based on ctDNA results. ctDNA test performance was compared to carcinoembryonic antigen (CEA) test results using McNemar's test. (3) Results: Our study cohort consisted of 87 patients treated with locoregional interventions who underwent ctDNA testing. The initial ctDNA test post-intervention was positive in 28 patients and negative in 59 patients. The median follow-up time was 14.0 months. Detectable ctDNA post-intervention was significantly associated with early disease recurrence, with a median disease-free survival (DFS) of 6.63 months compared to 21.30 months in ctDNA-negative patients (p < 0.001). ctDNA detected a numerically higher proportion of recurrences than CEA (p < 0.097). Post-intervention systemic therapy was not associated with improved DFS (p = 0.745). (4) Conclusions: ctDNA results are prognostically important in oligometastatic CRC, and further prospective studies are urgently needed to define its role in guiding clinical decisions.

Stereotactic Body Radiotherapy for Oligoprogression in Castration-Resistant Prostate Cancer: Early Toxicity Analysis of the TRAP Trial.

AIMS: To assess toxicity and patient quality of life after stereotactic body radiotherapy (SBRT) to oligoprogressive disease (OPD) in patients with metastatic castrate-resistant prostate cancer (CRPC) on androgen receptor targeted agents (ARTA). MATERIAL AND METHODS: This phase II trial enrolled patients with metastatic CRPC with ≤ 2 oligoprogressive lesions in bone, lymph node, lung, or prostate. All patients were receiving systemic treatment with abiraterone or enzalutamide at the time of oligoprogression. All patients received SBRT to the OPD site(s) and continued the current ARTA. Patients received 30 Gy in 5 fractions (alternate days) to the OPD site. The primary endpoint of the trial is to assess if SBRT to OPD sites results in progression free survival of >6 months. The primary endpoint for this toxicity analysis is the rate of grade 3 or higher adverse events at any timepoint up to 6 months after SBRT. Secondary endpoints included comparing pre- and post-SBRT patient-related outcomes reported using visual analogue scale scores and EQ-5D health questionnaire. RESULTS: Forty enrolled patients had at least 6 months of follow-up at the time of analysis. Grade 3 or higher toxicity from any cause recorded using common terminology criteria for adverse events and radiation therapy oncology group was found in 8/40 (20%) of patients, but only 1/40 (2.5%) was deemed possibly related to SBRT. There was no significant difference in mean EQ5D visual analogue scale score from baseline to each timepoint after SBRT (p = 0.449). CONCLUSION: In this prospective phase II clinical trial for OPD whilst on ARTA in the CRPC setting, we report low grade ≥ 3 toxicity after SBRT. There is no discernible change in patient-reported quality of life due to SBRT treatment. The final results of progression-free survival and toxicity of SBRT treatment will be reported once further follow-up is complete.

Assessing survival in non-small cell lung cancer brain metastases after stereotactic radiosurgery: before and after the start of the targetable mutation era.

PURPOSE: Targeted treatment options for non-small cell lung cancer (NSCLC) brain metastases (BMs) may be combined with stereotactic radiosurgery (SRS) to optimize survival. We assessed patient outcomes after SRS for NSCLC BMs, identifying survival trajectories associated with targetable mutations. METHODS: In this retrospective time-dependent analysis, we analyzed median overall survival of patients who received ≥ 1 SRS courses for BM from NSCLC from 2001 to 2021. We compared survival of patients with and without targetable mutations based on clinical variables and treatment. RESULTS: Among the 213 patients included, 87 (40.8%) had targetable mutations-primarily EGFR (22.5%)-and 126 (59.2%) did not. Patients with targetable mutations were more often female (63.2%, p <.001) and nonsmokers (58.6%, p <.001); had higher initial lung-molGPA (2.0 vs. 1.5, p <.001) and lower cumulative tumor volume (3.7 vs. 10.6 cm3, p <.001); and received more concurrent (55.2% vs. 36.5%, p =.007) and total (median 3 vs. 2, p <.001) systemic therapies. These patients had lower mortality rates (74.7% vs. 91.3%, p <.001) and risk (HR 0.298 [95%CI 0.190-0.469], p <.001) and longer median overall survival (20.2 vs. 7.4 months, p <.001), including survival ≥ 3 years (p =.001). Survival was best predicted by SRS with tumor resection in patients with non-targetable mutations (HR 0.491 [95%CI 0.318-757], p =.001) and by systemic therapy with SRS for those with targetable mutations (HR 0.124 [95%CI 0.013-1.153], p =.067). CONCLUSION: The presence of targetable mutations enhances survival in patients receiving SRS for NSCLC BM, particularly when used with systemic therapies. Survival for patients without targetable mutations was longest with SRS and surgical resection. These results inform best practices for managing patients with NSCLC BM based on driver mutation status.

Likelihood-of-harm/help of microsurgery compared to radiosurgery in large vestibular schwannoma.

PURPOSE: It has been shown that in large vestibular schwannomas (VS), radiosurgery (SRS) is inferior with respect to tumor control compared to microsurgical resection (SURGERY). However, SURGERY poses a significantly higher risk of facial-function deterioration (FFD). The aim of this study was to illustrate the effectiveness in terms of number-needed-to-treat/operate (NNO), number-needed-to-harm (NNH), and likelihood-of-harm/help (LHH) by comparing both treatment modalities in large VS. METHODS: This was a retrospective, dual-center cohort study. Tumor size was classified by Hannover Classification. Absolute risk reduction and risk increase were used to derive additional estimates of treatment effectiveness, namely NNO and NNH. LHH was then calculated by a quotient of NNH/NNO to illustrate the risk-benefit-ratio of SURGERY. RESULTS: Four hundred and forty-nine patients treated met the inclusion criteria. The incidence of tumor recurrence was significantly higher in SRS (14%), compared to SURGERY (3%) resulting in ARR of 11% and NNO of 10. At the same time, SURGERY was related to a significant risk of FFD resulting in an NNH of 12. Overall, the LHH calculated at 1.20 was favored SURGERY, especially in patients under the age of 40 years (LHH = 2.40), cystic VS (LHH = 4.33), and Hannover T3a (LHH = 1.83) and T3b (LHH = 1.80). CONCLUSIONS: Due to a poorer response of large VS to SRS, SURGERY is superior with respect to tumor control. One tumor recurrence can be prevented, when 10 patients are treated by SURGERY instead of SRS. Thus, LHH portrays the benefit of SURGERY in large VS even when taking raised FFD into account.

Narrative review of stereotactic body radiation therapy combined with tyrosine kinase inhibitors for oligometastatic EGFR-mutated non-small cell lung cancer: present and future developments.

Background and Objective: A significant number of individuals diagnosed with non-small cell lung cancer (NSCLC) have distant metastases, and the concept of oligometastatic NSCLC has shown promise in achieving a cure. Stereotactic body radiation therapy (SBRT) is currently considered a viable treatment option for a limited number of tumor metastases. It has also been demonstrated that third-generation tyrosine kinase inhibitors (TKIs) are effective in extending the survival of patients with epidermal growth factor receptor (EGFR)-mutated NSCLC. Hence, the combination of SBRT with third-generation TKIs holds the potential to enhance treatment efficacy in patients with oligometastatic EGFR-mutated NSCLC. This review aimed to assess the possibility of combining SBRT with TKIs as an optimum treatment option for patients with oligometastatic EGFR-mutated NSCLC. Methods: We performed a narrative review by searching the PubMed, Web of Science, Elsevier and ClinicalTrials.gov databases for articles published in the English language from January 2009 to February 2024 and by reviewing the bibliographies of key references to identify important literature related to combining SBRT with third-generation TKIs in oligometastatic EGFR-mutated NSCLC. Key Content and Findings: This review aimed to assess the viability of combining SBRT and EGFR-TKIs in oligometastatic EGFR-mutated NSCLC. Current clinical trials suggest that the combined therapies have better progression free survival (PFS) when using SBRT as either concurrent with EGFR-TKIs or consolidated with EGFR-TKIs. Furthermore, research with third-generation EGFR-TKIs and SBRT combinations has demonstrated tolerable toxicity levels without significant additional adverse effects as compared to prior therapies. However, further clinical trials are required to establish its effectiveness. Conclusions: The combined approach of SBRT and TKIs can effectively impede the progression of oligometastatic NSCLC in patients harboring EGFR mutations and, most notably, can prolong progression-free survival rates. However, the feasibility of combining SBRT with third-generation TKIs in clinical trials remains unclear.

Ruptured distal anterior inferior cerebellar artery aneurysm years after stereotactic radiosurgery for vestibular schwannoma: A case report and literature review.

Background: Aneurysmal formation after stereotactic radiosurgery (SRS) for vestibular schwannoma (VS) is a rare complication. Its characteristics and the best treatment strategies remain controversial, and the clinical course is especially unknown because reported aneurysms are first incidentally detected, or aneurysmal rupture occurs suddenly, and they are treated immediately. Case Description: A 68-year-old man who underwent SRS for VS 20 years ago presented with subarachnoid hemorrhage (SAH) due to rupture of a radiation-induced fusiform anterior inferior cerebellar artery aneurysm. He was treated with parent artery occlusion, resulting in a modified Rankin scale grade 2. This report illustrates the first case of detected aneurysm formation before rupture with retrospective magnetic resonance imaging evaluation. Conclusion: We describe the possible risk of rapid progression and rupture of aneurysms, focusing on the interval from SRS to aneurysmal formation. The period of formation of SRS-induced aneurysms is suspected to vary from years to decades regardless of radiation doses; however, aneurysms estimated as pseudoaneurysms have an extremely high risk of rupture within a few years, even when small in size. If aneurysms are discovered unruptured, there are some advantages in not only the prevention of poor prognosis due to SAH but also in the availability of optional therapeutic strategies using revascularization. Long-term annual follow-up, including vessel examination, is warranted not only to assess tumor status but also for early detection of any vascular lesions.

Predictors of radiation-induced changes in arteriovenous malformation patients undergoing radiosurgery: Insights from a Malaysian linear accelerator cohort.

Background: Radiation-induced changes (RICs) post-stereotactic radiosurgery (SRS) critically influence outcomes in arteriovenous malformation (AVM) treatments. This study aimed to identify predictors of RICs, described the types and severity of RICs, and assessed their impact on patient's functional outcomes to enhance risk assessment and treatment planning for AVM patients. Methods: This retrospective study analyzed 87 AVM patients who underwent SRS at Hospital Kuala Lumpur between January 2015 and December 2020. RICs were identified through detailed magnetic resonance imaging evaluations, and predictive factors were determined using multiple logistic regression. Functional outcomes were assessed with the modified Rankin scale (mRS). Results: Among the cohort, 40.2% developed RICs, with radiological RICs in 33.3%, symptomatic RICs in 5.7%, and permanent RICs in 1.1%. Severity categorization revealed 25.3% as Grade I, 13.8% as Grade II, and 1.1% as Grade III. Notably, higher Pollock-Flickinger scores and eloquence location were significant predictors of RIC occurrence. There was a significant improvement in functional outcomes post-SRS, with a marked decrease in non-favorable mRS scores from 8.0% pre-SRS to 1.1% post-SRS (P = 0.031). Conclusion: The study identified the eloquence location and Pollock-Flickinger scores as predictors of RICs post-SRS. The significant reduction in non-favorable mRS scores post-SRS underscores the efficacy of SRS in improving patient outcomes. Their results highlighted the importance of personalized treatment planning, focusing on precise strategies to optimize patient outcomes in AVM management, reducing adverse effects while improving functional outcomes.

Clinical Applicability and Safety of Conventional Frame-Based Stereotactic Techniques for Stereoelectroencephalography.

Objective: Stereoelectroencephalography (SEEG) is increasingly being recognized as an important invasive modality for presurgical evaluation of epilepsy. This study focuses on the clinical and technical considerations of SEEG investigations when using conventional frame-based stereotaxy, drawing on institutional experience and a comprehensive review of relevant literature. Methods: This retrospective observational study encompassed the surgical implantation of 201 SEEG electrodes in 16 epilepsy patients using a frame-based stereotactic instrument at a single tertiary-level center. We provide detailed descriptions of the operative procedures and technical nuances for bilateral and multiple SEEG insertions, along with several illustrative cases. Additionally, we present a literature review on the technical aspects of the SEEG procedure, discussing its clinical implications and potential risks. Results: Frame-based SEEG electrode placements were successfully performed through sagittal arc application, with the majority (81.2%) of cases being bilateral and involving up to 18 electrodes in a single operation. The median skin-to-skin operation time was 162 minutes (interquartile range [IQR], 145-200), with a median of 13 minutes (IQR, 12-15) per electrode placement for time efficiency. There were two occurrences (1.0%) of electrode misplacement and one instance (0.5%) of a postoperative complication, which manifested as a delayed intraparenchymal hemorrhage. Following SEEG investigation, 11 patients proceeded with surgical intervention, resulting in favorable seizure outcomes for nine (81.8%) and complete remission for eight cases (72.7%). Conclusion: Conventional frame-based stereotactic techniques remain a reliable and effective option for bilateral and multiple SEEG electrode placements. While SEEG is a suitable approach for selected patients who are strong candidates for epilepsy surgery, it is important to remain vigilant concerning the potential risks of electrode misplacement and hemorrhagic complications.

Urinary organs-at-risk for prostate cancer external beam radiotherapy: contouring guidelines on behalf of the Francophone Group of Urological Radiation Therapy (GFRU).

PURPOSE: Occurrence of genitourinary (GU) toxicity is a common adverse event observed after external beam radiotherapy (EBRT) for prostate cancer (PCa). Recent findings suggest that the dose delivered to specific urinary organs-at-risk (OARs) such as ureters, bladder trigone, and urethra is involved in the development of GU toxicity. METHODS AND MATERIALS: A multidisciplinary task force including three radiation oncologists, a uroradiologist, and a urologist was created in 2022. First, OARs potentially involved in GU toxicity were identified and discussed. A literature review was performed, addressing several questions relative to urinary OARs: anatomical and radiological definition, radiation-induced injury, dose-volume parameters. Secondly, results were presented and discussed with a panel of radiation oncologists, members of the "Francophone Group of Urological Radiation Therapy" (GFRU). Thereafter, GFRU experts were asked to answer a dedicated questionnaire, including 35 questions on the controversial issues related to the delineation of urinary OARs. RESULTS: The following structures were identified as critical for PCa EBRT: ureters, bladder, bladder neck, bladder trigone, urethra (intraprostatic, membranous, spongious), striated sphincter, and post-enucleation or post-transurethral resection of the prostate (TURP) cavity. A consensus was obtained for 32 out of 35 items. CONCLUSION: This consensus highlights contemporary urinary structures in both upper and lower urinary tract to be considered for EBRT treatment planning of PCa. The current recommendations also propose a standardized definition of urinary OARs, for both daily practice and future clinical trials.

Ablative Radiation Therapy to Restrain Everything Safely Treatable (ARREST): A Phase I study of Stereotactic Ablative Radiotherapy (SABR) for poly-metastatic disease.

PURPOSE: This phase 1 study aimed to assess the safety and feasibility of SABR delivery to all sites of polymetastatic disease (>10 metastases). METHODS AND MATERIALS: A 3+3 study design was used with five dose levels from 6 Gy (6 Gy x 1) to 30 Gy (6 Gy weekly x 5). Dose-limiting toxicity (DLT) was defined as any grade 4 or 5 toxicity, or more than three grade 3 toxicities within six weeks of treatment. The primary endpoint was the maximal tolerated dose, defined as the dose level where ≥ 2/6 of patients experienced DLT. Secondary endpoints included quality of life (QOL; FACT-G and EQ-5D-5L) at 6-weeks post-treatment, progression-free survival (PFS) and overall survival (OS). RESULTS: Thirteen patients were accrued: 12 Gy (n=3), 18 Gy (n=3), 24 Gy (n=4), 30 Gy (n=3) and 207 lesions were treated. Nine patients (69%) had acute toxicity: grade 1 (n=6, 46%), grade 2 (n=2, 15%; n=1 pneumonitis and n=1 fatigue) and grade 3 (n=1, 7.7%, neutropenia). There were no grade 4 or 5 toxicities. Mean ± SD QOL (FACT-G and EQ-5D-5L health state) was 80.4 ± 21.9 and 77.4 ± 20.9 at baseline versus 76.4 ± 21.8 and 68.0 ± 24.2 at 6-week follow-up (p=0.009 and p=0.055, respectively). With a median follow-up of 8.7 months post-treatment (IQR: 2.4-24 months), 8 of 13 patients had disease progression (62%). The median and 12-month PFS were 3.6 months and 11.3% respectively. The median and 12-month OS were 13.8 months and 62% respectively. CONCLUSIONS: In this phase I trial, SABR for polymetastatic disease was technically feasible with acceptable acute toxicity at dose levels up to 30 Gy (6 Gy weekly x 5). DLT was not observed.