Fractionated stereotactic radiotherapy of intracranial postoperative cavities after resection of brain metastases - Clinical outcome and prognostic factors.

Background and Purpose: After surgical resection of brain metastases (BM), radiotherapy (RT) is indicated. Postoperative stereotactic radiosurgery (SRS) reduces the risk of local progression and neurocognitive decline compared to whole brain radiotherapy (WBRT). Aside from the optimal dose and fractionation, little is known about the combination of systemic therapy and postoperative fractionated stereotactic radiotherapy (fSRT), especially regarding tumour control and toxicity. Methods: In this study, 105 patients receiving postoperative fSRT with 35 Gy in 7 fractions performed with Cyberknife were retrospectively reviewed. Overall survival (OS), local control (LC) and total intracranial brain control (TIBC) were analysed via Kaplan-Meier method. Cox proportional hazards models were used to identify prognostic factors. Results: Median follow-up was 20.8 months. One-year TIBC was 61.6% and one-year LC was 98.6%. Median OS was 28.7 (95%-CI: 16.9-40.5) months. In total, local progression (median time not reached) occurred in 2.0% and in 20.4% radiation-induced contrast enhancements (RICE) of the cavity (after median of 14.3 months) were diagnosed. Absence of extracranial metastases was identified as an independent prognostic factor for superior OS (p = <0.001) in multivariate analyses, while a higher Karnofsky performance score (KPS) was predictive for longer OS in univariate analysis (p = 0.041). Leptomeningeal disease (LMD) developed in 13% of patients. Conclusion: FSRT after surgical resection of BM is an effective and safe treatment approach with excellent local control and acceptable toxicity. Further prospective randomized trials are needed to establish standardized therapeutic guidelines.

Stereotactic radiosurgery and radiotherapy for brainstem metastases: An international multicenter analysis.

Brainstem metastases (BSM) present a significant neuro-oncological challenge, resulting in profound neurological deficits and poor survival outcomes. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) offer promising therapeutic avenues for BSM despite their precarious location. This international multicenter study investigates the efficacy and safety of SRS and FSRT in 136 patients with 144 BSM treated at nine institutions from 2005 to 2022. The median radiographic and clinical follow-up periods were 6.8 and 9.4 months, respectively. Predominantly, patients with BSM were managed with SRS (69.4%). The median prescription dose and isodose line for SRS were 18 Gy and 65%, respectively, while for FSRT, the median prescription dose was 21 Gy with a median isodose line of 70%. The 12-, 24-, and 36-month local control (LC) rates were 82.9%, 71.4%, and 61.2%, respectively. Corresponding overall survival rates at these time points were 61.1%, 34.7%, and 19.3%. In the multivariable Cox regression analysis for LC, only the minimum biologically effective dose was significantly associated with LC, favoring higher doses for improved control (in Gy, hazard ratio [HR]: 0.86, p < .01). Regarding overall survival, good performance status (Karnofsky performance status, ≥90%; HR: 0.43, p < .01) and prior whole brain radiotherapy (HR: 2.52, p < .01) emerged as associated factors. In 14 BSM (9.7%), treatment-related adverse events were noted, with a total of five (3.4%) radiation necrosis. SRS and FSRT for BSM exhibit efficacy and safety, making them suitable treatment options for affected patients.

Fractionated stereotactic radiotherapy in craniopharyngiomas: A systematic review and single arm meta-analysis.

INTRODUCTION: Numerous studies have demonstrated Fractionated Stereotactic Radiotherapy's (FSRT) effectiveness in tumor control post-resection for craniopharyngiomas. Nevertheless, past literature has presented conflicting findings particularly regarding endocrine and visual function outcomes. This study aims to elucidate FSRT's efficacy and safety for this population. METHODS: Adhering to PRISMA, a systematic review and meta-analyses was conducted. Included studies had to report the effects of FSRT for treating craniopharyngiomas in a sample greater than four patients, addressing at least one of the outcomes of interest: improvement in visual acuity or field, new-onset hypopituitarism, effectiveness, and tumor progression. Relative risk with 95% confidence intervals were used to assess the outcomes. RESULTS: After retrieving a total of 1292 studies, 10 articles met the predefined criteria and thus were finally selected, amounting to a total of 256 patients. The improvement in visual acuity was estimated at 45% (95% CI: 6-83%), while the improvement in the visual field was 22% (95% CI: 0-51%). Regarding endocrine function, the new-onset hypopituitarism rate was found to be 5% (95% CI: 0-11%). Relative to FSRT effectiveness, the pooled estimate of the complete tumor response rate was 17% (95% CI: 4-30%), and the tumor progression rate was 7% (95% CI: 1-13%). Also, a 3-year progression-free survival rate of 98% (95% CI: 95-100%) was obtained. CONCLUSION: Despite limitations and risks, FSRT shows promise as a viable therapeutic option for craniopharyngiomas, offering notable benefits for visual functions and tumor control. Further research is required to better understand the associated risks, benefits, and clinical utility.

Evaluating contouring accuracy and dosimetry impact of current MRI-guided adaptive radiation therapy for brain metastases: a retrospective study.

BACKGROUND: Magnetic resonance imaging (MRI) guided adaptive radiotherapy (MRgART) has gained increasing attention, showing clinical advantages over conventional radiotherapy. However, there are concerns regarding online target delineation and modification accuracy. In our study, we aimed to investigate the accuracy of brain metastases (BMs) contouring and its impact on dosimetry in 1.5 T MRI-guided online adaptive fractionated stereotactic radiotherapy (FSRT). METHODS: Eighteen patients with 64 BMs were retrospectively evaluated. Pre-treatment 3.0 T MRI scans (gadolinium contrast-enhanced T1w, T1c) and initial 1.5 T MR-Linac scans (non-enhanced online-T1, T2, and FLAIR) were used for gross target volume (GTV) contouring. Five radiation oncologists independently contoured GTVs on pre-treatment T1c and initial online-T1, T2, and FLAIR images. We assessed intra-observer and inter-observer variations and analysed the dosimetry impact through treatment planning based on GTVs generated by online MRI, simulating the current online adaptive radiotherapy practice. RESULTS: The average Dice Similarity Coefficient (DSC) for inter-observer comparison were 0.79, 0.54, 0.59, and 0.64 for pre-treatment T1c, online-T1, T2, and FLAIR, respectively. Inter-observer variations were significantly smaller for the 3.0 T pre-treatment T1c than for the contrast-free online 1.5 T MR scans (P < 0.001). Compared to the T1c contours, the average DSC index of intra-observer contouring was 0.52‒0.55 for online MRIs. For BMs larger than 3 cm3, visible on all image sets, the average DSC indices were 0.69, 0.71 and 0.64 for online-T1, T2, and FLAIR, respectively, compared to the pre-treatment T1c contour. For BMs < 3 cm3, the average visibility rates were 22.3%, 41.3%, and 51.8% for online-T1, T2, and FLAIR, respectively. Simulated adaptive planning showed an average prescription dose coverage of 63.4‒66.9% when evaluated by ground truth planning target volumes (PTVs) generated on pre-treatment T1c, reducing it from over 99% coverage by PTVs generated on online MRIs. CONCLUSIONS: The accuracy of online target contouring was unsatisfactory for the current MRI-guided online adaptive FSRT. Small lesions had poor visibility on 1.5 T non-contrast-enhanced MR-Linac images. Contour inaccuracies caused a one-third drop in prescription dose coverage for the target volume. Future studies should explore the feasibility of contrast agent administration during daily treatment in MRI-guided online adaptive FSRT procedures.

Efficacy of Dose-Escalated Hypofractionated Radiosurgery for Arteriovenous Malformations.

There is considerable controversy about the management of arteriovenous malformations (AVMs) that are high risk for surgical resection. Stereotactic radiosurgery (SRS) has a reported success rate of less than 50% with unacceptably high rates of radiation necrosis with larger AVM volumes. Neither volume staging nor hypo-fractionated SRS have conclusively been demonstrated to improve results. We hypothesized that the failure of previous hypo-fractionation SRS trials was due to an insufficient biologically effective dose (BED) of radiation. We initiated a pilot study of treating AVM patients with a total dose divided into three or five fractions designed to deliver the equivalent BED of 20 Gy in a single fraction (α/ß =3). We performed a retrospective analysis of 37 AVM patients who had a minimum of two years of follow-up or underwent obliteration. Patients were treated with 30 Gy/3 fractions, 33 Gy/3 fractions, or 40 Gy/5 fractions using a CyberKnife device (Accuracy Incorporated, Madison, Wisconsin, United States). The primary endpoint was complete AVM obliteration, determined by MRA imaging. Most obliterations were confirmed with diagnostic cerebral angiography. Secondary endpoints were post-radiosurgery hemorrhage and radiation-related necrosis. Kaplan-Meier analysis was used to determine obliteration rates. From 2013 to 2021, 37 patients fitting inclusion criteria were identified (62% male, average age at treatment = 48.88 years). Fifteen (41%) patients had prior treatment (surgery, radiosurgery, embolization) for their AVM, 32 (86%) had AVMs in eloquent locations, 17 (46%) had high-risk features, and 14 (38%) experienced AVM rupture prior to treatment. The average modified radiosurgery-based AVM score (mRBAS) was 1.81 (standard deviation (SD)= 0.52), and the mean AVM volume was 6.77 ccs (SD = 6.09). Complete AVM obliteration was achieved in 100% of patients after an average of 26.13 (SD = 14.62) months. The Kaplan-Meier analysis showed AVM obliteration rates at one, two, and three years to be 16.2%, 46.9%, and 81.1%, respectively. Post-operative AVM rupture or hemorrhage occurred in one (2.7%) patient, after nine months. Radiation necrosis occurred in four (11%) patients after an average period of 17.3 (SD =14.7) months. The SRS dose used in this study is the highest BED of any AVM hypofractionation trial in the published literature. This study suggests that dose-escalated hypofractionated radiosurgery can be a successful strategy for AVMs with acceptable long-term complication rates. Further investigation of this treatment regimen should be performed to assess its efficacy.

Stereotactic radiosurgery of brain metastases: a retrospective study.

BACKGROUND: Single-fraction stereotactic radiosurgery (SRS) is an established standard for radiation therapy of brain metastases although recent developments indicate that multi-fractionated stereotactic radiotherapy (FSRT) results in lower radiation necrosis especially for larger metastases, and the same or even better local control in comparison to SRS. METHODS: Seventy-two patients with 111 brain metastases received SRS with a single dose of 18 Gy between September 2014 and December 2021. The dose prescription was either 18 Gy given to the enclosing 80% isodose with a normalization to Dmax = 100% of 22.5 Gy (part I) or 18 Gy = D98, while D0.03 cc of 21.6-22.5 Gy was accepted (part II). The study retrospectively evaluated local progression-free survival (LPFS), response on the first follow-up magnetic resonance imaging (MRI), and radiation necrosis. RESULTS: Melanoma brain metastases (n = 44) were the most frequent metastases. The median gross tumor volume (GTV) was 0.30 cm³ (IQR, 0.17-0.61). The median follow-up time of all patients was 50.8 months (IQR, 30.4-64.6). Median LPFS was 23.5 months (95%CI 17.2, 29.8). The overall LPFS rates at 12-, 18-, 24- and 30 months were 65.3%, 56.3%, 46.5%, and 38.8%. Brain metastases with radioresistant histology (melanoma, renal cell cancer, and sarcoma) showed a 12-month LPFS of 60.2%, whereas brain metastases with other histology had a 12-month LPFS of 70.1%. The response of brain metastases on first follow-up MRIs performed after a median time of 47 days (IQR, 40-63) was crucial for long-term local control and survival. Eight brain metastases (7.2%) developed radiation necrosis after a median time of 18.4 months (IQR, 9.4-26.5). In multivariate analyses, a GTV > 0.3 cm³ negatively affected LPFS (HR 2.229, 95%CI 1.172, 4.239). Melanoma, renal cell cancers, and sarcoma had a lower chance of LPFS in comparison to other cancer types (HR 2.330, 95%CI 1.155, 4.699). CONCLUSIONS: Our results indicate a reasonable 1-year local control of brain metastases with radiosensitive histology. Radioresistant metastases show a comparatively poor local control. Treatment refinements merit exploration to improve local control of brain metastases. TRIAL REGISTRATION: This study is retrospectively registered (ethics approval number 23-3451-104).

Comparison of Staged Stereotactic Radiosurgery and Fractionated Stereotactic Radiotherapy in Patients with Brain Metastases > 2 cm without Prior Whole Brain Radiotherapy: A Systematic Review and Meta-Analysis.

OBJECTIVE: To compare fractionated stereotactic radiotherapy (FSRT) with staged stereotactic radiosurgery (SSRS) in patients with brain metastases >2 cm without prior whole brain radiotherapy. METHODS: In this systematic review and meta-analysis, PubMed, Scopus, Web of Science, Embase, and Cochrane were searched to include studies that evaluated FSRT and/or SSRS for brain metastases >2 cm or 4 cm3 in adult patients with a known primary malignancy and no prior history of whole brain radiotherapy. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed and an indirect random-effect meta-analyses was conducted to compare treatment outcomes between the two modalities. RESULTS: A total of 10 studies were included, comprising 612 (778 metastases) and 250 patients (265 metastases) in the SSRS and FSRT groups, respectively. The SSRS group had significantly older patients (66.6 ± 17.51 years vs. 62.37 ± 37.89 years; P = 0.029) with lower rate of control of primary disease (11.59% vs. 78.7%, P < 0.00001), and more patients with Karnofsky performance status ≥70 at baseline (92.81% vs. 88.56%; P = 0.045). FSRT was associated with a statistically nonsignificant but clinically important lower 12-month overall survival (44.75% [95% confidence interval [CI]: 30.48%-59.95%] vs. 53.25% [95%CI: 45.15%-61.19%], P = 0.1615) and higher rate of salvage radiotherapy (18.18% [95%CI: 8.75%-34%] vs. 12.27% [95%CI: 5.98%-23.53%], P = 0.0841). Both groups had comparable rates of local tumor control, mortality, tumor progression, recurrence, neurological death, and 6-month overall survival. CONCLUSIONS: SSRS and FSRT were found to be comparable for treating brain metastases >2 cm not previously irradiated. Given the paucity of such studies, trials directly comparing the two treatment strategies are warranted to support these findings.

Meningioma Presenting With Intratumoral Hemorrhage on Active Surveillance.

Meningiomas are relatively common primary adult brain tumors. They are slow-growing, highly vascular, and graded according to histology, phenotypic and genotypic features. We present a case of a 66-year-old male with a history of tongue squamous cell carcinoma, which presented multiple risk factors for cardiovascular and thromboembolic events. A brain lesion was initially detected on a computed tomography (CT) scan and later characterized by magnetic resonance imaging (MRI). The multidisciplinary team decided to maintain surveillance due to the lack of associated symptoms. Upon expansion in size and acute intralesional hemorrhage seen on follow-up imaging, the patient was submitted to surgical excision. The histopathological testing determined it to be an atypical meningioma. Two months later, the patient received stereotactic radiotherapy, and a post-surgical MRI showed no evidence of tumor recurrence. This case report describes a rare occurrence of intratumoral hemorrhage in a meningioma during surveillance, highlighting the importance of vigilant monitoring and consideration of potential risk factors for hemorrhagic events.

Pretreatment lymphocyte-to-monocyte ratio as a prognostic factor and influence on dose-effect in fractionated stereotactic radiotherapy for oligometastatic brain metastases in non-small cell lung cancer patients.

Background: Studies on the prognostic factors for patients with brain oligo-metastasis treated with fractionated stereotactic radiotherapy (FSRT) usually focus on the size of metastatic tumor and radiation dose. Some inflammatory indicators have predictive value in non-small cell lung cancer (NSCLC) with brain metastasis receiving stereotactic radiotherapy. However, the prognostic value of inflammatory indicators in NSCLC patients with brain oligo-metastasis treated with FSRT, and their effect on radiotherapy dose is unknown. Methods: A total of 95 advanced NSCLC patients with brain oligo-metastasis who had undergone FSRT treatment at Ningbo Medical Center Lihuili Hospital between January 2015 and April 2022 were enrolled into the study. Neutrophil to lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR), tumor diameter and biologically effective dose (BED10) were analyzed using Chi-square test. Univariate and multivariate Cox regressions were used to identify predictors of survival. Results: Tumor diameter (< 2 cm), BED10 (≥ 48Gy) and LMR (≥ 4) were found to be independently associated with good intracranial local control survival (i-LCS) through multivariate analysis. The median i-LCS was longer in patients with 2 independent risk factors (tumor diameter ≥ 2 and LMR < 4) administered with BED10 > 53.6Gy compared with patients administered with BED10 ≤ 53.6Gy (20.7 months vs 12.0 months, P = 0.042). LMR ≥ 4 (P = 0.019) and positivity for driver gene mutations (P = 0.011) were independently associated with better overall survival (OS). Conclusions: LMR is an independent prognostic factor of i-LCS and OS in NSCLC patients with brain oligo-metastasis treated with FSRT. Patients with tumor diameter ≥ 2 and LMR < 4 should be treated with BED10 greater than 53.6Gy.

Single fraction stereotactic radiosurgery and fractionated stereotactic radiotherapy provide equal prognosis with overall survival in patients with brain metastases at diagnosis without surgery at primary site.

Background and purpose: Stereotactic radiosurgery (SRS) and fractionated stereotactic radiation therapy (SRT) are both treatments shown to be effective in treating brain metastases (BMs). However, it is unknown how these treatments compare in effectiveness and safety in cancer patients with BMs regardless of the primary cancer. The main objective of this study is to investigate the SRS and SRT treatments' associations with the overall survival (OS) of patients diagnosed with BMs using the National Cancer Database (NCDB). Materials and methods: Patients in the NCDB with breast cancer, non-small cell lung cancer, small cell lung cancer, other lung cancers, melanoma, colorectal cancer, or kidney cancer who had BMs at the time of their primary cancer diagnosis and received either SRS or SRT as treatment for their BMs were included in the study. We analyzed OS with a Cox proportional hazard analysis that adjusted variables associated with improved OS during univariable analysis. Results: Of the total 6,961 patients that fit the criteria for the study, 5,423 (77.9%) received SRS and 1,538 (22.1%) received SRT. Patients who received SRS treatment had a median survival time of 10.9 (95% CI [10.5-11.3]), and those who received SRT treatment had a median survival time of 11.3 (95% CI [10.4-12.3]) months. This difference was not found to be significant (Log-rank P = 0.31). Multivariable Cox proportional hazard analysis did not yield a significant difference between the treatments' associations with OS (Hazard Ratio: 0.942, CI 95% [0.882-1.006]; P = .08) or SRS vs. SRT. Conclusions: In this analysis, SRS and SRT did not show a significant difference in their associations with OS. Future studies investigating the neurotoxicity risks of SRS as compared to SRT are warranted.

Radiation Necrosis Following Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy with High Biologically Effective Doses for Large Brain Metastases.

In Radiation Therapy Oncology Group 90-05, the maximum tolerated dose of single-fraction radiosurgery (SRS) for brain metastases of 21-30 mm was 18 Gy (biologically effective dose (BED) 45 Gy12). Since the patients in this study received prior brain irradiation, tolerable BED may be >45 Gy12 for de novo lesions. We investigated SRS and fractionated stereotactic radiotherapy (FSRT) with a higher BED for radiotherapy-naive lesions. Patients receiving SRS (19-20 Gy) and patients treated with FSRT (30-48 Gy in 3-12 fractions) with BED > 49 Gy12 for up to 4 brain metastases were compared for grade ≥ 2 radiation necrosis (RN). In the entire cohort (169 patients with 218 lesions), 1-year and 2-year RN rates were 8% after SRS vs. 2% and 13% after FSRT (p = 0.73) in per-patient analyses, and 7% after SRS vs. 7% and 10% after FSRT (p = 0.59) in per-lesion analyses. For lesions ≤ 20 mm (137 patients with 185 lesions), the RN rates were 4% (SRS) vs. 0% and 15%, respectively, (FSRT) (p = 0.60) in per-patient analyses, and 3% (SRS) vs. 0% and 11%, respectively, (FSRT) (p = 0.80) in per-lesion analyses. For lesions > 20 mm (32 patients with 33 lesions), the RN rates were 50% (SRS) vs. 9% (FSRT) (p = 0.012) in both per-patient and per-lesion analyses. In the SRS group, a lesion size > 20 mm was significantly associated with RN; in the FSRT group, lesion size had no impact on RN. Given the limitations of this study, FSRT with BED > 49 Gy12 was associated with low RN risk and may be safer than SRS for brain metastases > 20 mm.

Fractionated stereotactic radiotherapy of brain metastases: results of a retrospective study.

BACKGROUND: Lasting local control of brain metastases following stereotactic radiotherapy is becoming increasingly relevant since systemic treatment constantly improves the prognosis of patients with extracranial metastases. METHODS: 73 patients with 103 brain metastases received hypofractionated stereotactic radiotherapy (FSRT) in 6 fractions of 5 Gy between January 2017 and December 2021 at the University Hospital Regensburg, Germany. The study retrospectively evaluated local progression free survival (LPFS), overall survival (OS) and distant brain progression free survival (DPFS) of patients without prior radiotherapy of the brain. Response rate and brain radiation necrosis were reported. Cox proportional hazard models evaluated prognostic factors of OS and LPFS. RESULTS: The median patient age was 61.0 years (Interquartile range, IQR 51.0, 67.5). The most common tumor types were malignant melanoma (34.2%) and non-small cell lung adenocarcinoma (26.0%). The median gross tumor volume (GTV) was 0.9 cm³ (IQR 0.4, 3.6). The median follow-up time of all patients was 36.3 months (95%CI 29.1, 43.4). The median OS was 17.4 months (95%CI 9.9, 24.9). Overall survival rates at 6-, 12-, 18-, 24-, and 30 months were 81.9%, 59.1%, 49.0%, 41.3%, and 37.2%, retrospectively. The mean LPFS was 38.1 months (95%CI 31.4, 44.9), while the median LPFS has not been reached. LPFS rates at 6-, 12-, 18-, 24- and 30 months were 78.9%, 68.7%, 64.3%, 61.6% and 58.7%, retrospectively. Median DPFS of all patients was 7.7 months (95%CI 6.1, 9.3). Six, 12-, 18-, 24- and 30 months DPFS rates were 62.1%, 36.3%, 31.1%, 24.8% and 21.7%. Five brain metastases (4.8%) developed brain radiation necrosis. In multivariate analysis, the number of brain metastases negatively affected LPFS. Non-melanoma and non-renal cell cancer was associated with a higher chance of LPFS in comparison to other cancer. A GTV > 1.5 cm³ translated into a higher risk of death compared to a GTV ≤ 1.5 cm³ and Karnofsky performance score was predictive of OS. CONCLUSIONS: FSRT in 6 fractions of 5 Gy seems to be an effective treatment with an acceptable local control for patients with brain metastases although melanoma and renal cell cancer seem to have a worse local control in comparison to other cancer. TRIAL REGISTRATION: This study is retrospectively registered.

Stereotactic Body Radiotherapy as an Effective Treatment for Pancreatic Cancer.

Background Stereotactic body radiotherapy (SBRT) allows the delivery of an ablative radiation dose to the tumor with minimal toxicity. Although magnetic resonance imaging (MRI)-guided SBRT appears to be a promising approach in the modern era, X-ray image-guided SBRT is still used worldwide for pancreatic cancer. This study aims to evaluate the results of X-ray image-guided SBRT in patients with locally advanced pancreatic cancer (LAPC). Methodology Medical records of 24 patients with unresectable LAPC who underwent X-ray image-guided SBRT between 2009 and 2022 were retrospectively evaluated. SPSS version 23.0 (IBM Corp., Armonk, NY, USA) was utilized for all analyses. Results The median age was 64 years (range = 42-81 years), and the median tumor size was 3.5 cm (range = 2.7-4 cm). The median total dose of SBRT was 35 Gy (range = 33-50 Gy) in five fractions. After SBRT, 30% of patients showed complete and 41% showed partial response, whereas 20% had stable disease and 9% had progression. Median follow-up was 15 months (range = 6-58 months). During follow-up, four (16%) patients had local recurrence, one (4%) had a regional recurrence, and 17 (70%) had distant metastasis (DM). The two-year local control (LC), local recurrence-free survival (LRFS), overall survival (OS), and DM-free survival (DMFS) rate was 87%, 36%, 37%, and 29%, respectively. In univariate analysis, a larger tumor size (>3.5 cm) and higher cancer antigen 19-9 level (>106.5 kU/L) significantly decreased the OS, LRFS, and DMFS rates. No severe acute toxicity was observed. However, two patients had severe late toxicity as intestinal bleeding. Conclusions X-ray image-guided SBRT provides a good LC rate with minimal toxicity for unresectable LAPC. However, despite modern systemic treatments, the rate of DM remains high which plays a major role in survival.

Treatment Outcomes After Higher-dose Fractionated Stereotactic Radiotherapy (FSRT) Alone for 1-4 Brain Metastases.

BACKGROUND/AIM: Fractionated stereotactic radiotherapy (FSRT) is increasingly used for brain metastases. We investigated higher-dose FSRT with biologically effective doses (BED) of 49.6-66.7 Gy12 Patients and Methods: Eleven characteristics were evaluated for local control (LC), overall survival (OS), and freedom from radiation necrosis (RN) in 69 patients with 1-4 brain metastases. Fifty-seven patients (83%) had extracranial metastases, 23 (33%) Karnofsky performance scores (KPS) ≤70, and 21 (30%) brain metastases ≥21 mm. RESULTS: At 1 and 2 years, LC-rates were 81% and 63%, OS-rates 66% and 43%, and freedom from RN-rates 98% and 87%, respectively. Median time to local progression was 35 months, median survival 19 months. KPS ≥90 was associated with better OS (p=0.048). BED of 49.6-57 Gy12 (vs. 63-66.7 Gy12) was associated with higher rates of freedom from RN (p=0.046), not with LC (p=0.78) or OS (p=0.55). CONCLUSION: Higher-dose FSRT appears feasible and effective in patients with 1-4 brain metastases. BED 63-66.7 Gy12 may not improve LC and OS but may increase RN risk.

Stereotactic Radiotherapy or Whole-Brain Irradiation Plus Simultaneous Integrated Boost After Resection of Brain Metastases.

BACKGROUND/AIM: Most patients with resected brain metastases receive post-operative radiotherapy. This study investigated outcomes of fractionated stereotactic radiotherapy (FSRT) alone or whole-brain irradiation plus simultaneous integrated boost (WBI+SIB) in the post-operative setting. PATIENTS AND METHODS: Forty-four patients receiving FSRT alone (n=32) or WBI+SIB (n=12) after resection of 1-3 brain metastases from 2014-2022 were analyzed. Twelve factors were evaluated for local control (LC), distant brain control (DBC), and overall survival (OS). RESULTS: On univariate and multivariate analyses, single brain metastasis was associated with improved LC and DBC. Longer interval between tumor diagnosis and radiotherapy, single brain metastasis, and Karnofsky performance score >80 were associated with improved OS. WBI+SIB showed a trend towards better DBC. CONCLUSION: Several independent predictors of outcomes after FSRT or WBI+SIB following resection of brain metastases were identified. Given similar survival in the post-operative setting between FSRT and WBI+SIB, potential toxicity remains a significant factor in treatment recommendations.

Symptomatic Brain Radiation Necrosis in an Anaplastic Lymphoma Kinase (ALK)-Positive Non-small Cell Lung Cancer (NSCLC) Patient After Fractionated Stereotactic Radiotherapy While on Alectinib.

Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) has a higher incidence of brain metastasis. Despite having a favorable prognosis and relatively long survival with second-generation ALK tyrosine kinase inhibitors (TKI), patients can have substantial morbidity, negatively affecting functional progression-free and symptom-free survival. Studies have shown that ALK-rearranged NSCLC is a risk factor for developing radiation necrosis (RN). Recently, second-generation TKI, especially lorlatinib, alectinib, and brigatinib, have demonstrated good central nervous system (CNS) penetration and overall response rates in patients with brain metastasis. However, to improve overall outcomes in symptomatic or limited brain metastases, stereotactic radiosurgery (SRS) is increasingly preferred over whole brain radiotherapy (WBRT) prior to systemic therapy to avoid significant cognitive deterioration. To improve the therapeutic ratio, fractionated stereotactic radiotherapy (FSRT) has been explored for brain metastasis. Herein, we report on one ALK-rearranged NSCLC patient who developed RN despite FSRT, one year after the completion of radiotherapy while on alectinib.

An exploratory analysis of MR-guided fractionated stereotactic radiotherapy in patients with brain metastases.

Purpose: To assess the feasibility and potential benefits of online adaptive MR-guided fractionated stereotatic radiotherapy (FSRT) in patients with brain metastases (BMs). Methods and materials: Twenty-eight consecutive patients with BMs were treated with FSRT of 30 Gy in 5 fractions on the 1.5 T MR-Linac. The FSRT fractions employed daily MR scans and the contours were utilized to create each adapted plan. The brain lesions and perilesional edema were delineated on MR images of pre-treatment simulation (Fx0) and all fractions (Fx1, Fx2, Fx3, Fx4 and Fx5) to evaluate the inter-fractional changes. These changes were quantified using absolute/relative volume, Dice similarity coefficient (DSC) and Hausdorff distance (HD) metrics. Planning target volume (PTV) coverage and organ at risk (OAR) constraints were used to compare non-adaptive and adaptive plans. Results: A total of 28 patients with 88 lesions were evaluated, and 23 patients (23/28, 82.1%) had primary lung adenocarcinoma. Significant tumor volume reduction had been found during FSRT compared to Fx0 for all 88 lesions (median -0.75%, -5.33%, -9.32%, -17.96% and -27.73% at Fx1, Fx2, Fx3, Fx4 and Fx5, p < 0.05). There were 47 (47/88, 53.4%) lesions being accompanied by perilesional edema and the inter-fractional changes were significantly different compared to those without perilesional edema (p < 0.001). Patients with multiple lesions (13/28, 46.4%) had more significant inter-fractional tumor changes than those with single lesion (15/28, 53.6%), including tumor volume reduction and anatomical shift (p < 0.001). PTV coverage of non-adaptive plans was below the prescribed coverage in 26/140 fractions (19%), with 12 (9%) failing by more than 10%. All 140 adaptive fractions met prescribed target coverage. The adaptive plans also had lower dose to whole brain than non-adaptive plans (p < 0.001). Conclusions: Significant inter-fractional tumor changes could be found during FSRT in patients with BMs treated on the 1.5 T MR-Linac. Daily MR-guided re-optimization of treatment plans showed dosimetric benefit in patients with perilesional edema or multiple lesions.

Direct dosimetric comparison of linear accelerator vs. Gamma Knife fractionated stereotactic radiotherapy (fSRT) of large brain tumors.

The purpose of this study was to directly compare the plan quality of Gamma Knife (GK) (Elekta, Stockholm, Sweden)- vs linear accelerator (LINAC)-based delivery techniques for fractionated stereotactic radiotherapy (fSRT) of large brain metastases. Eighteen patients with clinical target volumes (CTVs) larger than 9.5 cc were selected to generate comparative plans for the prescription dose of 9 Gy × 3 fractions, utilizing the Eclipse (Varian, Palo Alto, US) vs Leksell GammaPlan (LGP) (Elekta, Stockholm, Sweden) treatment planning systems (TPS). Each GK plan was first developed using LGP's automatic planning, followed by manual adjustments/refinements. The same MRI and structures, including CTVs and organs at risk, were then DICOM-transferred to the Eclipse TPS. Volumetric Modulated Arc Therapy (VMAT) and Dynamic Conformal Arc (DCA) plans for a Truebeam, with high-definition multi-leaf collimators (MLCs), were developed on these MR images and structures using a single isocenter and 3 non-coplanar arcs. No planning target volume (PTV) margins were added, and no heterogeneity correction was used for either TPS. GK plans were prescribed to the 50% isodose line, and Eclipse VMAT and DCA plans allowed a maximum dose up to 170% and ∼125%, respectively. Gradient index (GI), Paddick Conformity Index (PCI), V20GyRind, and V4GyRind of all 3 techniques were calculated and compared. One-way analysis of variance (ANOVA) was performed to determine the statistical significance of the differences of these planning indices for the 3 planning techniques. A total of eighteen treatment targets were analyzed. Median CTV volume was 14.4 cc (range 9.5 cc - 55.9 cc). Mean ± standard deviation of PCI were 0.85 ± 0.03, 0.90 ± 0.03, and 0.72 ± 0.11 for GK, VMAT and DCA plans, respectively. They were respectively 2.64 ± 0.17, 2.46 ± 0.18, and 2.83 ± 0.48 for GI; 15.33 ± 8.45 cc, 10.47 ± 4.32 cc and 23.51 ± 16 cc for V20GyRind; and 316.28 ± 138.35 cc, 317.81 ± 108.21 cc, and 394.85 ± 142.16 cc for V4GyRind. The differences were statistically significant with p < 0.01 for all indices, except for V4GyRind (p > 0.129). In conclusion, a direct dosimetric comparison using the same MRI scan and contours was performed to evaluate the plan quality of various fSRT delivery techniques for CTV > 9.5 cc. LINAC VMAT plans provided the best dosimetric outcome in regard to PCI, GI, and V20GyRind. GK outcomes were similar to LINAC VMAT plans while LINAC DCA outcomes were significantly worse. Even though GK has a smaller physical penumbra, LINAC VMAT outperformed GK in this study due to enhanced penumbra sharpening and better beam optimization.

Vestibular Schwannoma Hypofractionated Stereotactic Radiation Therapy in Five Fractions.

AIM: To retrospectively analyse the long-term results of hypofractionated stereotactic radiation therapy (HSRT) applied in five fractions for vestibular schwannomas. MATERIALS AND METHODS: One hundred and thirty-four patients with vestibular schwannomas underwent medical treatment of HSRT. The median follow-up time interval was 54 months (range 6-121 months). All patients had a prescribed dose of 22 Gy in five fractions to D90. Restaging was carried out by thin-slice contrast-enhanced T1 magnetic resonance imaging. Progression was defined as 2 mm post-treatment tumour enlargement. Progression or death for any reason was counted as an event in progression-free survival rates. Acute toxicity was defined as adverse events occurring within 3 months of HSRT; long-term toxicity was defined as such events occurring after 3 months. RESULTS: In 74/128 patients who had >6 months of follow-up (54%), the HSRT resulted in a partial or a complete response. The mean time interval for response in 50% of these was 4 years, whereas in 49 patients (38%) vestibular schwannomas failed to show any response, resulting in stable disease. Five of 128 patients (4%) showed marked progressive vestibular schwannomas after treatment in the first 3 years; two of them received conventionally fractionated radiation therapy. Local control at 3, 5 and 7 years was 96%, 95% and 94%, respectively. Seven were lost to follow-up. The median planning target volume was 2.1 ml (range 0.78-8.66). The 3- and 5-year progression-free survival rates were 95% and 94%, respectively. Seven patients reported a marked deterioration in hearing ability. Post-radiation therapy magnetic resonance imaging showed variability in oedema collection, but no patient suffered from radio-necrosis. Grade 2 temporary facial nerve disorders were observed in 10 patients (8%) 3-6 months after HSRT. CONCLUSION: Delivering HSRT in five fractions for vestibular schwannoma appears safe and efficient, combining both efficiency and short treatment time while optimising neurological function preservation.

Dosimetric evaluation of adult and paediatric brain tumours planned using mask-based cobalt-60 fractionated stereotactic radiotherapy compared to linear accelerator-based volumetric modulated arc therapy.

INTRODUCTION: We conducted a study to evaluate the dosimetric feasibility of mask-based cobalt-60 fractionated stereotactic radiotherapy (mcfSRT) with the Leksell Gamma Knife® Icon™ device. METHODS: Eleven patients with intracranial tumours were selected for this dosimetry study. These patients, previously treated with volumetric arc therapy (VMAT), were re-planned using mcfSRT. Target volume coverage, conformity/gradient indices, doses to organs at risk and treatment times were compared between the mcfSRT and VMAT plans. Two-sided paired Wilcoxon signed-rank test was used to compare differences between the two plans. RESULTS: The V95 for PTV was similar between fractionated mcfSRT and VMAT (P = 0.47). The conformity index and gradient indices were 0.9 and 3.3, respectively, for mcfSRT compared to 0.7 and 4.2, respectively, for VMAT (P < 0.001 and 0.004, respectively). The radiation exposure to normal brain was lower for mcfSRT across V10, V25 and V50 compared with VMAT (P = 0.007, <0.001 and <0.001, respectively). The median D0.1cc for optic nerve and chiasm as well as the median D50 to the hippocampi were lower for mcfSRT compared to VMAT. Median beam-on time for mcfSRT was 9.7 min per fraction, compared to 0.9 min for VMAT (P = 0.002). CONCLUSION: mcfSRT plans achieve equivalent target volume coverage, improved conformity and gradient indices, and reduced radiation doses to organs at risk as compared with VMAT plans. These results suggest superior dosimetric parameters for mcfSRT plans and can form the basis for future prospective studies.