Large Brain Metastases Research Articles

Adjuvant hypofractionated stereotactic radiotherapy after resection of single large brain metastasis in patients with oligo-metastatic disease: a strategy finally validated?

Adjuvant hypofractionated stereotactic radiotherapy after resection of single large brain metastasis in patients with oligo-metastatic disease: a strategy finally validated?

Brain surgery in combination with tyrosine kinase inhibitor and whole brain radiotherapy for epidermal growth factor receptor-mutant non-small-cell lung cancer with brain metastases

The role of brain surgery (BS) on the survival of patients with non-small-cell lung cancer (NSCLC) and brain metastases (BM), particularly those with epidermal growth factor receptor (EGFR) mutations under tyrosine kinase inhibitors (TKIs) is yet to be defined. We aimed to investigate whether BS could improve the survival of patients in addition to the combination of TKIs and whole brain radiotherapy (WBRT). A cohort of 1394 NSCLC patients between 2011 and 2016 was retrospectively studied. One hundred patients with BM receiving TKI + RT were enrolled. Forty patients (40%) received TKI + BS + RT, and 60 patients (60%) received TKI + RT. Survival time was calculated from the date of BM diagnoses to the date of death or last follow-up. With a median follow-up of 25.6 months (95% CI, 18.6–35.7), the median survival after BM was 18.2 months (95% CI, 10.8 to 27.4) in the TKI + BS + RT group and 11.8 months (95% CI, 5.2 to18) in the TKI + RT group. Cox proportional hazards regression model for the patients with the largest BM over 1 cm showed that TKI + BS + RT group was associated with improved survival relative to TKI + RT group (HR, 0.49; 95% CI, 0.29 to 0.83; P = 0.008). BS adds significant survival benefits in addition to TKIs and WBRT, especially for patients with EGFR-mutant NSCLC and the largest BM over 1 cm.

NIMG-43. LONGITUDINAL TRACKING AND GROWTH RATE CHARACTERIZATION OF BRAIN METASTASES ON MAGNETIC RESONANCE IMAGING

Abstract PURPOSE Measuring treatment response is vital for assessing efficacy of treatment regimen for patients with brain metastases (BM). Unfortunately, manual delineation of all lesions on MRI across time-points is prohibitively time-consuming, making it infeasible to track individual lesion growth/shrinkage rates as part of the clinical workflow. To overcome this challenge, we propose a deep learning approach to segment all BM, and furthermore, show that certain brain regions are more prone to high-growth rate lesions. METHODS 163 longitudinal MRIs from 77 patients with MPRAGE-post contrast imaging protocol were prospectively obtained from Massachusetts General Hospital (MGH). An expert neuro-oncologist provided ground truth segmentations for all patients. A 3D U-Net architecture was trained to automatically segment BM; training was stopped when validation set Dice score plateaued to prevent overfitting. To enable lesion tracking, all time-points per patient were affinely registered to each other. Every lesion was subsequently classified based on its growth rate (responder: overall lesion shrinkage; inconclusive: 0% to 40% lesion growth; non-responder: more than 40% lesion growth). Characterization of global lesion growth rate patterns was accomplished by affinely registering all time-points to the MNI brain atlas. Segmented lesions were projected onto the atlas, which was qualitatively analyzed to identify spatial regions composed primarily of one class of lesion. RESULTS For automatic segmentation, we report a mean dice score of 0.778, 0.737, and 0.704 on training, validation, and testing sets respectively. Furthermore, we find that the largest BM with the highest average growth rate (non-responders) tend to be located in the posterior frontal/parietal lobes, while smaller, lower growth rate lesions (responders) tend to be localized in the frontal lobes. The posterior fossa was found to be heterogeneous in lesion size and growth rate. CONCLUSION We developed automatic metastatic lesion tracking over time-points and identified brain regions associated with differing growth rate lesions.

CMET-03. MANAGEMENT OF MULTIPLE BRAIN METASTASES BY STAGED SRS FOCUSING ON UTMOST RISK LESIONS

Abstract BACKGROUND Patients with multiple large brain metastases (LBMs) are subject to cause intracranial hypertension, which remains a clinical difficulty so far. The present study is to investigate whether staged stereotactic radiosurgery (SRS) is a feasible solution to improve clinical symptoms and life quality in palliative management. METHODS Patients with brain metastases treated between 1 January 2016 and 30 March 2019 were retrospectively studied. The patients inclusion criteria included were: 1) metastatic lesions ≥ 3; 2) tumor lesions with a supratentorial invasion ≥ 3 cm or a subtentorial invasion ≥ 2 cm; 3) with neurological impairment or with a high risk for intracranial hypertension. The first stage of SRS dose regimens for utmost risk supratentorial lesions were 20-24Gy within 2-fractions (fx); whereas 24Gy/3-fx for subtentorial lesions. For the 2nd stage, the rest metastatic lesions with relatively lower risk were treated with 16-18Gy/1-fx one week after that. RESULTS A total of 30 patients were enrolled included in this study. The neurological symptoms were significantly relieved following 1st stage of SRS, with a median period of 3 days (2–14 days). 13 out of 30 patients were randomly selected for MR imaging two weeks after SRS. It suggested that 84.6% (11/13) of the patients were observed with a clear reduction of tumor volume. The median reduced diameter was 0.38 (0.17–0.83) cm and a median volume reduction was 3.22 (0.01–9.08) mm3. According to RANO-BM, the objective remission rate of utmost risk lesions was 100%, whereas the less critical lesions was 95.16% (59/62). One patient (3.33%) was identified with acute adverse reaction (> grade 3). CONCLUSIONS Staged SRS with a priority for utmost risk lesions was indicated to be an effective approach for multiple large brain metastases. Further prospective study is highly warranted.

Hypofractionated stereotactic radiotherapy for challenging brain metastases using 36 Gy in six fractions

PurposeStereotactic radiosurgery and hypofractionated stereotactic radiotherapy are standard treatments for brain metastases when they are small in size (at the most 3cm in diameter) and limited in number, in patients with controlled extracerebral disease and a good performance status. Large inoperable brain metastases usually undergo hypofractionated stereotactic radiotherapy while haemorrhagic brain metastases have often been contraindicated for both stereotactic radiosurgery or hypofractionated stereotactic radiotherapy. The objective of this retrospective study was to assess a six 6Gy-fractions hypofractionated stereotactic radiotherapy scheme in use at our institution for haemorrhagic brain metastases, large brain metastases (size greater than 15cm3) or brain metastases located next to critical structures. Material and methodsPatients with brain metastases treated with the 6×6Gy scheme since 2012 to 2016 were included. Haemorrhagic brain metastases were defined by usual criteria on CT scan and MRI. Efficacy, acute and late toxicity were evaluated. ResultsSixty-two patients presenting 92 brain metastases were included (32 haemorrhagic brain metastases). Median follow up was 10.1 months. One-year local control rate for haemorrhagic brain metastases, large brain metastases, or brain metastases next to critical structures were 90.7%, 73% and 86.7% respectively. Corresponding overall survival rates were 61.2%, 32% and 37.8%, respectively. Haemorrhagic complications occurred in 5.3% of patients (N=5), including two cases of brain metastases with pretreatment haemorrhagic signal. Tolerance was good with only one grade 3 acute toxicity. ConclusionThe 6×6Gy hypofractionated stereotactic radiotherapy scheme seems to yield quite good results in patients with haemorrhagic brain metastases, which must be confirmed in a prospective way.

MRI appearance change during stereotactic radiotherapy for large brain metastases and importance of treatment plan modification during treatment period

PurposeWe aimed to evaluate the magnetic resonance imaging (MRI) appearance changes during stereotactic radiotherapy (SRT) for large sized brain metastases, and analyze the lesions necessitating treatment plan modification.Materials and methodsA total of 23 patients (27 lesions, >2 cm in tumor diameter) underwent SRT and all lesions were evaluated the appearance changes which had the necessity of the treatment plan modification. The appearance change of tumor during SRT was evaluated using gadolinium-enhanced MRI. The reasons of the modification were classified into tumor reduction, tumor enlargement, displacement, and shape change.ResultsAmong the 27 lesions, 55.6% required the treatment plan modification. The reasons were tumor reduction in six lesions, tumor enlargement in three lesions, displacement in three lesions, and shape change in three lesions. The planning target volume (PTV) size changed up to 43.0% and the shift of center of PTV was a maximum of 1.7 mm. The pathological status (adenocarcinoma vs others) and timing of steroid administration (prior vs after SRT start) were the predictive factors of tumor changes required the modification.ConclusionsAs tumor changes might occur even during short period of SRT, the treatment plan evaluation and modification were important in SRT for large brain metastases.

407P - Management of multiple brain metastases by staged SRS focusing on utmost risk lesions

BackgroundPatients with multiple large brain metastases (LBMs) are subject to cause intracranial hypertension, which remains a clinical difficulty so far. The present study is to investigate whether staged stereotactic radiosurgery (SRS) is a feasible solution to improve clinical symptoms and life quality in palliative management. MethodsPatients with brain metastases treated between 1 January 2016 and 30 March 2019 were retrospectively studied. The patients inclusion criteria included were: 1) metastatic lesions ≥ 3; 2) tumor lesions with a supratentorial invasion ≥ 3cm or a subtentorial invasion ≥ 2cm; 3) with neurological impairment or with a high risk for intracranial hypertension. The first stage of SRS dose regimens for utmost risk supratentorial lesions were 20-24Gy within 2-fractions (fx); whereas 24Gy/3-fx for subtentorial lesions. For the 2nd stage, the rest metastatic lesions with relatively lower risk were treated with 16-18Gy/1-fx one week after that. ResultsA total of 30 patients were enrolled included in this study. The neurological symptoms were significantly relieved following 1st stage of SRS, with a median period of 3 days (2-14 days). 13 out of 30 patients were randomly selected for MR imaging two weeks after SRS. It suggested that 84.6% (11/13) of the patients were observed with a clear reduction of tumor volume. The median reduced diameter was 0.38 (0.17-0.83) cm and a median volume reduction was 3.22 (0.01-9.08) mm3. According to RANO-BM, the objective remission rate of utmost risk lesions was 100%, whereas the less critical lesions was 95.16% (59/62). One patient (3.33%) was identified with acute adverse reaction (> grade 3). ConclusionsStaged SRS with a priority for utmost risk lesions was indicated to be an effective approach for multiple large brain metastases. Further prospective study is highly warranted. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Hypofractionated Radiosurgery Plus Bevacizumab for Locally Recurrent Brain Metastasis with Previously High-Dose Irradiation

Selection of appropriate treatment for patients with recurrent brain metastasis (BM) remains uncertain. Recent studies have demonstrated a significant response rate and acceptable toxicity using fractionated stereotactic radiosurgery (FSRS) in patients with locally recurrent large BM. The aim of this study was to evaluate efficacy and toxicity of FSRS with bevacizumab as a new salvage treatment for locally recurrent BM with previous high-dose irradiation. Patients with recurrent BM previously irradiated were enrolled. Salvage FSRS dose was 9.5-29 Gy (2-5 fractions) with 62%-75% isodose line by CyberKnife according to the brain tumor volume, site, and previous dose. Bevacizumab was prescribed for 4 cycles (5 mg/kg, every 3 weeks). The primary objective was to identify the overall survival after salvage treatment. Secondary objectives included clinical response (Karnofsky performance scale), imaging response (magnetic resonance imaging) and treatment-related adverse events. From December 2009 to October 2016, 24 patients were enrolled. The 1-year overall survival after salvage stereotactic radiosurgery was 87.5%. Twenty-three (96%) patients had a positive imaging response with a T2 volume reduction range of 6-22 cm3 (median 14 cm3, P= 0.032, paired t test). Significant clinical improvement was achieved (best Karnofsky performance scale score, P < 0.05, paired t test). Grade 1/2 fatigue was observed in 8 (33%) patients. Grade 3 fatigue and headache occurred in 1 patient. FSRS with adjuvant bevacizumab treatment showed favorable clinical and radiologic control as a salvage treatment regimen. The diagnoses of radiation necrosis and local recurrence after salvage FSRS warrant further study.

Interfractional Target Volume Changes in Brain Metastases during 13-Fraction Stereotactic Radiotherapy

Advances in systemic therapy have greatly improved the prognosis of patients with brain metastases (BMs); long-term local control and reduced radiation toxicity are important. Fractionated stereotactic radiotherapy (SRT) seems to be associated with a reduced risk of radiation necrosis while providing equivalent local control compared to single-fraction or hypofractionated radiosurgery and is used in our institution for patients with a good prognosis or large BMs. As 13-fraction SRT lasts at least 17 days, we conduct adaptive replanning as necessary, based on contrast-enhanced mid-treatment magnetic resonance imaging (MRI) performed during 13-fraction SRT. We retrospectively analyzed interfractional volume changes and clinical outcomes of BMs treated with 13-fraction SRT. In total, this study included 23 patients with 27 BMs who received 13-fraction SRT with dynamic conformal arc therapy between July 2015 and November 2018. We excluded patients who received postoperative radiotherapy for the surgical cavity, no contrast-enhanced mid-treatment MRI, or single isocenter volumetric-modulated arc therapy for multiple BMs. The median patient age was 70 years and the median Karnofsky Performance Status was 90. There were 15 lung-cancer patients. The planning target volume (PTV) was established by adding a 1-mm margin to the gross tumor volume (GTV), defined as the volume of the contrast-enhancing lesion. The peripheral dose prescribed to the PTV was 39–44.2 Gy in 13 fractions. The GTV of the initial SRT plan (initial GTV) and the modified GTV based on the mid-treatment MRI scan (mid-treatment GTV) were compared. The median initial GTV was 3.8 (range 0.2–26.7) cm3 and the median period from the start of SRT to the mid-treatment MRI scan was 6 (range 3–11) days. In 10 lesions, the mid-treatment GTV had changed by more than 20% (5 had increased and 5 decreased) relative to the initial GTV. Adaptive replanning was conducted for 14 lesions. Of the 10 lesions that had increased or decreased in size by more than 20%, 8 received adaptive replanning. There was no significant relationship between an interfractional GTV volume change of more than 20%, primary disease (lung cancer vs. other cancers), and the presence of necrotic or cystic components. Regarding clinical outcomes, both overall survival rates and local control rates at 6 months were 95.0%, with a median follow-up period of 7.2 months. Two patients experienced grade 3 cerebral edema, two experienced grade 3 seizures, and four experienced grade 1 brain necrosis (CTCAE v5). The mid-treatment GTV changed by more than 20% relative to the initial GTV in almost one-third of lesions receiving 13-fraction SRT. More cases and long-term follow up are required to verify the impact of interfractional volume changes and adaptive replanning on clinical outcomes.

Outcome evaluation of patients treated with fractionated Gamma Knife radiosurgery for large (> 3 cm) brain metastases: a dose-escalation study.

Fractionated Gamma Knife radiosurgery (GKS) represents a feasible option for patients with large brain metastases (BM). However, the dose-fractionation scheme balanced between local control and radiation-induced toxicity remains unclear. Therefore, the authors conducted a dose-escalation study using fractionated GKS as the primary treatment for large (> 3 cm) BM. The exclusion criteria were more than 3 lesions, evidence of leptomeningeal disease, metastatic melanoma, poor general condition, and previously treated lesions. Patients were randomized to receive 24, 27, or 30 Gy in 3 fractions (8, 9, or 10 Gy per fraction, respectively). The primary endpoint was the development of radiation necrosis assessed by a neuroradiologist blinded to the study. The secondary endpoints included the local progression-free survival (PFS) rate, change in tumor volume, development of distant intracranial progression, and overall survival. Between September 2016 and April 2018, 60 patients were eligible for the study, with 46 patients (15, 17, and 14 patients in the 8-, 9-, and 10-Gy groups, respectively) available for analysis. The median follow-up duration was 9.6 months (range 2.5-25.1 months). The 6-month estimated cumulative incidence of radiation necrosis was 0% in the 8-Gy group, 13% (95% confidence interval [CI] 0%-29%) in the 9-Gy group, and 37% (95% CI 1%-58%) in the 10-Gy group. Being in the 10-Gy group was a significant risk factor for the development of radiation necrosis (p = 0.047; hazard ratio [HR] 7.2, 95% CI 1.1-51.4). The 12-month local PFS rates were 65%, 80%, and 75% in the 8-, 9-, and 10-Gy groups, respectively. Being in the 8-Gy group was a risk factor for local treatment failure (p = 0.037; HR 2.5, 95% CI 1.1-29.6). The mean volume change from baseline was a 47.5% decrease in this cohort. Distant intracranial progression and overall survival did not differ among the 3 groups. In this dose-escalation study, 27 Gy in 3 fractions appeared to be a relevant regimen of fractionated GKS for large BM because 30 Gy in 3 fractions resulted in unacceptable toxicities and 24 Gy in 3 fractions was associated with local treatment failure.

RADI-02. SINGLE-SESSION VERSUS MULTISESSION GAMMA KNIFE RADIOSURGERY FOR LARGE BRAIN METASTASES FROM NON-SMALL CELL LUNG CANCER: RETROSPECTIVE ANALYSIS

PURPOSE: To evaluate the efficacy of Gamma Knife radiosurgery (GKS) in patients with large brain metastases by comparing single-session radiosurgery (S-GKS) and multisession radiosurgery (M-GKS), the authors retrospectively analyzed the clinical outcomes of the patients who underwent GKS for brain metastases from non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Between January 2010 and December 2016, 66 patients with 74 lesions >=10 cm3 from large brain metastases from only NSCLC were included. Fifty-five patients with 60 lesions were treated with S-GKS; 11 patients with 14 lesions were treated with M-GKS. Median doses were 16 Gy (range, 11–18 Gy) for the S-GKS group and 8 Gy (range, 7–10 Gy) in three fractions for the M-GKS group. RESULTS: With a mean follow-up period of 13.1 months (range, 1.3–76.4 months), the median survival duration was 21.1 months for all patients. Median tumor volume was 14.3 cm3 (range, 10.0–58.3). The local control rate was 77.0% and the progression-free survival rate was 73.6% at the last follow-up. There were no significant between-group differences in terms of local control rate (p = 0.10). Compared with S-GKS, M-GKS did not differ significantly in radiation-induced complications (38.1% versus 45.4%, p = 0.83). While eight patients who underwent S-GKS experienced major complications of grade >=3, no toxicity was observed in patients treated with M-GKS. CONCLUSIONS: M-GKS may be an effective alternative for large brain metastases from NSCLC. Specifically, severe radiation-induced toxicity (≥ grade 3) did not occur in M-GKS for large-volume metastases. Although the long-term effects and results from larger samples remain unclear, M-GKS may be a suitable palliative treatment to preserve neurological function.

RADI-28. UP-FRONT SINGLE SESSION RADIOSURGERY FOR LARGE BRAIN METASTASES - VOLUMETRIC RESPONSES AND OUTCOMES

OBJECTIVE: Patients presenting with large brain metastases (LBM), described in the literature as ≥2.5 cm in maximum diameter or ≥10cm3in volume, pose a management challenge. For patients not compromised by mass effect, corticosteroid therapy followed by SRS allows for efficient, minimal access care that facilitates immediate institution of systemic therapy. METHODS: We performed a volumetric-based analysis in order to determine the efficacy of single-session SRS in the treatment of LBM in comparison to other treatment modalities. Thirty patients over the age of 18 with systemic cancer and brain metastases (≥2.7cm in greatest diameter or ≥10cm3in volume) who underwent single session SRS were included. Serial tumor volumes, clinical outcomes, and medication requirements were studied. RESULTS: Among 30 patients, 70% of patients had either lung, melanoma, or breast cancer. Median initial tumor size (maximum diameter) was 32mm (range 28–43) and median initial tumor volume was 9.32cm3 (range 1.09–25.31). Median marginal dose was 16Gy (range 12–18). Average percent decrease in tumor volume was 50% on imaging at 4–8 weeks, 60% at 4–6 months, 48% at 6–8 months, and 67% at >8 months compared to initial imaging. Only one patient required a subsequent craniotomy 4 years after SRS for an enlarging cyst which was granulation tissue consistent with radiation effects on pathology. There were no adverse events immediately following SRS. Median corticosteroid use after SRS was 21 days. There was no statistically significant difference in KPS score between treatment day and last follow up, suggesting relative safety and maintenance of function. CONCLUSION: Initial high dose corticosteroid therapy followed by prompt single session SRS is a safe and efficacious method of managing patients with large brain metastases (defined in our study as ≥2.7cm or ≥10cm3), if the clinical condition of the patient is acceptable at presentation.

RADI-44. MANAGEMENT OF MULTIPLE BRAIN METASTASES BY STAGED SRS FOCUSING ON UTMOST RISK LESIONS

BACKGROUND: Patients with multiple large brain metastases (LBMs) are subject to cause intracranial hypertension, which remains a clinical difficulty so far. The present study is to investigate whether staged stereotactic radiosurgery (SRS) is a feasible solution to improve clinical symptoms and life quality in palliative management. METHODS: Patients with brain metastases treated between 1 January 2016 and 30 March 2019 were retrospectively studied. The patients inclusion criteria included were: 1) metastatic lesions ≥ 3; 2) tumor lesions with a supratentorial invasion ≥ 3 cm or a subtentorial invasion ≥ 2 cm; 3) with neurological impairment or with a high risk for intracranial hypertension. The first stage of SRS dose regimens for utmost risk supratentorial lesions were 20-24Gy within 2-fractions (fx); whereas 24Gy/3-fx for subtentorial lesions. For the 2nd stage, the rest metastatic lesions with relatively lower risk were treated with 16-18Gy/1-fx one week after that. RESULTS: A total of 30 patients were enrolled included in this study. The neurological symptoms were significantly relieved following 1st stage of SRS, with a median period of 3 days (2–14 days). 13 out of 30 patients were randomly selected for MR imaging two weeks after SRS. It suggested that 84.6% (11/13) of the patients were observed with a clear reduction of tumor volume. The median reduced diameter was 0.38 (0.17–0.83) cm and a median volume reduction was 3.22 (0.01–9.08) mm3. According to RANO-BM, the objective remission rate of utmost risk lesions was 100%, whereas the less critical lesions was 95.16% (59/62). One patient (3.33%) was identified with acute adverse reaction (> grade 3). CONCLUSIONS: Staged SRS with a priority for utmost risk lesions was indicated to be an effective approach for multiple large brain metastases. Further prospective study is highly warranted.

RADI-05. FRACTIONATED TREATMENT OF BRAIN METASTASES WITH GAMMA KNIFE ICON

PURPOSE/OBJECTIVE(S): Stereotactic radiosurgery with Gamma Knife is a common treatment modality for patients with brain metastasis. The Gamma Knife ICON allows for immobilization with an aquaplast mask, permitting fractionated treatments. We describe one of the first experiences utilizing this technique with brain metastasis and evaluate outcomes. MATERIALS/METHODS: From June 2017 to November 2018, 29 patients with 43 separate intracranial lesions were treated with fractionated stereotactic radiotherapy using the gamma knife ICON at a single institution. Patients received between 20–30 Gy in 3–5 fractions with no margin over the course of 5 to 23 days. Local control was physician assessed. Local failure over time was modeled using cumulative incidence; lesions were censored at last radiographic follow up. RESULTS: Median tumor volume and prescription isodose was 7.7 cm3 (range 0.3–43.9) and 50% (range 40–65), respectively. Median radiographic follow-up was 7 months and median survival was 9 months. Radiation necrosis occurred in 3/3 patients treated with 27 Gy in 3 fractions, one requiring therapeutic resection. Incidence of local failure for all treated lesions was 9% at 1 year. Tumor volume >7 cm3 was associated with local failure on univariate analysis (p=0.025). 100% (2/2) lesions treated with 20 Gy in 5 fractions developed local recurrence. CONCLUSION: Fractionated stereotactic radiotherapy with the Gamma Knife ICON provides excellent local control for small and large brain metastases with minimal toxicity. Tumors >7 cm3 should receive at least 30 Gy in 5 fractions for optimal control. Treatment with 27 Gy in 3 fractions appears to have high rates of treatment related toxicity and should be avoided.

Focal Management of Large Brain Metastases and Risk of Leptomeningeal Disease

PurposeSurgery is often used for large or symptomatic brain metastases but is associated with risk of developing leptomeningeal dissemination. Emerging data suggest that fractionated stereotactic radiation therapy (FSRT) is an effective management strategy in large brain metastases. We sought to retrospectively compare leptomeningeal disease (LMD) and local control (LC) rates for patients treated with surgical resection followed by radiosurgery (S + SRS) versus FSRT alone. Methods and MaterialsWe identified all patients with a brain metastasis ≥3 cm in diameter treated from 2004 to 2017 with S + SRS or FSRT alone (25 or 30 Gy in 5 fractions) who had follow-up imaging. LMD was defined as focal or diffuse leptomeningeal enhancement that was >5 mm from the index metastasis. Categorical baseline characteristics were compared with the χ2 test. LMD and LC rates were evaluated by the Kaplan-Meier (KM) method, with the log-rank test used to compare subgroups. ResultsA total of 125 patients were identified, including 82 and 43 in the S + SRS and FSRT alone groups, respectively. Median pretreatment Graded Prognostic Assessment in the S + SRS and FSRT groups was 2.5 and 1.5, respectively (P < .001). Median follow-up was 7 months. The KM estimate of 12-month LMD rate in the S + SRS and FSRT groups was 45% and 19%, respectively (P = .048). The KM estimate of 12-month local control in the S + SRS and FSRT groups was 70% and 69%, respectively (P = .753). The 12-month KM estimate of grade ≥3 toxicity was 1.4% in S + SRS group versus 6.3% in the FSRT alone group (P = .248). After adjusting for graded prognostic assessment (GPA), no overall survival difference was observed between groups (P = .257). ConclusionsSurgery is appropriate for certain brain metastases, but S + SRS may increase LMD risk compared with FSRT alone. Because S + SRS and FSRT seem to have similar LC, FSRT may be a viable alternative to S + SRS in select patients with large brain metastases.

Retrospective analysis of hypofractionated stereotactic radiotherapy for tumors larger than 2 cm.

ABSTRACTStereotactic radiosurgery for large brain metastases (BM) not amenable to surgical resection is associated with limited local control and neurotoxicity, while hypofractionated stereotactic radiotherapy (HFSRT) has emerged as a promising option. We retrospectively evaluated 61 patients with BM larger than 2 cm in the maximum diameter, who were treated with HFSRT (mainly 35 Gy/5 fractions) in our center between 2006–2016, focusing on the effect of BM size on outcomes. Eligible patients were divided according to the maximum BM diameter (group A [23 patients]: ≥3 cm, group B [22 patients]: <3 cm) to assess the relationship between tumor size and prognosis or safety. The primary outcome was the local control rate (LCR), and secondary outcomes were the response rate (RR), brain progression-free survival (BPFS), median survival time (MST), and radionecrosis (RN). Univariate and multivariate analyses for LCR were conducted using Cox’s proportional hazards model. In the 45 eligible patients (58 lesions) enrolled in this study, the RR was 86.4% with an overall LCR of 64.7% at 12 months (67.1% for group A and 61.5% for group B [p = 0.45]). The median BPFS and MST were 11.6 and 14.2 months, respectively. Univariate analyses revealed that female patients and gynecological cancer patients had poorer LCR, but they were not significantly independent prognostic factors (p = 0.06, 0.09, respectively). Two patients (4.4%) experienced RN that was detected more than 4 years after HFSRT. We conclude that HFSRT is safe for large BM but further studies are needed to determine optimal doses and fractions.

Study of Intraoperative Radiotherapy for Patients With Large Brain Metastases Treated With Neurosurgical Resection

Study of Intraoperative Radiotherapy for Patients With Large Brain Metastases Treated With Neurosurgical Resection

Comparison of treatment results between 3- and 2-stage Gamma Knife radiosurgery for large brain metastases: a retrospective multi-institutional study.

In order to obtain better local tumor control for large (i.e., > 3 cm in diameter or > 10 cm3 in volume) brain metastases (BMs), 3-stage and 2-stage Gamma Knife surgery (GKS) procedures, rather than a palliative dose of stereotactic radiosurgery, have been proposed. Here, authors conducted a retrospective multi-institutional study to compare treatment results between 3-stage and 2-stage GKS for large BMs. This retrospective multi-institutional study involved 335 patients from 19 Gamma Knife facilities in Japan. Major inclusion criteria were 1) newly diagnosed BMs, 2) largest tumor volume of 10.0-33.5 cm3, 3) cumulative intracranial tumor volume ≤ 50 cm3, 4) no leptomeningeal dissemination, 5) no more than 10 tumors, and 6) Karnofsky Performance Status 70% or better. Prescription doses were restricted to between 9.0 and 11.0 Gy in 3-stage GKS and between 11.8 and 14.2 Gy in 2-stage GKS. The total treatment interval had to be within 6 weeks, with at least 12 days between procedures. There were 114 cases in the 3-stage group and 221 in the 2-stage group. Because of the disproportion in patient numbers and the pre-GKS clinical factors between these two GKS groups, a case-matched study was performed using the propensity score matching method. Ultimately, 212 patients (106 from each group) were selected for the case-matched study. Overall survival, tumor progression, neurological death, and radiation-related adverse events were analyzed. In the case-matched cohort, post-GKS median survival time tended to be longer in the 3-stage group (15.9 months) than in the 2-stage group (11.7 months), but the difference was not statistically significant (p = 0.65). The cumulative incidences of tumor progression (21.6% vs 16.7% at 1 year, p = 0.31), neurological death (5.1% vs 6.0% at 1 year, p = 0.58), or serious radiation-related adverse events (3.0% vs 4.0% at 1 year, p = 0.49) did not differ significantly. This retrospective multi-institutional study showed no differences between 3-stage and 2-stage GKS in terms of overall survival, tumor progression, neurological death, and radiation-related adverse events. Both 3-stage and 2-stage GKS performed according to the aforementioned protocols are good treatment options in selected patients with large BMs.

Early Clinical Outcomes for Intraoperative Radiotherapy Following Resection of Large Brain Metastases

Early Clinical Outcomes for Intraoperative Radiotherapy Following Resection of Large Brain Metastases

PO-0745 Fractionated SRS (fSRS) or surgery plus fSRS to resection cavity for NSCLC large brain metastases

PO-0745 Fractionated SRS (fSRS) or surgery plus fSRS to resection cavity for NSCLC large brain metastases