scholarly journals 07. RETROSPECTIVE ANALYSIS OF SALVAGE SURGERY FOR LOCAL PROGRESSION OF BRAIN METASTASIS PREVIOUSLY TREATED WITH STEREOTACTIC IRRADIATION: DIAGNOSTIC CONTRIBUTION, FUNCTIONAL OUTCOME, AND PROGNOSTIC FACTORS

2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii1-ii1
Author(s):  
Koichi Mitsuya ◽  
Shoichi Deguchi ◽  
Nakamasa Hayashi ◽  
Hideyuki Harada ◽  
Yoko Nakasu
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Brain Metastases ◽  
Salvage Surgery ◽  
Systemic Disease ◽  
Safety Margin ◽  
Rapid Improvement ◽  
Stereotactic Irradiation ◽  
Eloquent Areas ◽  
Local Progression

Abstract BACKGROUND Stereotactic irradiation (STI) is a primary treatment for patients with newly diagnosed brain metastases. Some of these patients experience local progression, which is difficult to differentiate from radiation necrosis, and difficult to treat. Just a few studies have clarified the prognosis and effectiveness of salvage surgery after STI. We evaluated the diagnostic value and improvement of functional outcomes after salvage surgery. METHODS We evaluated patients with brain metastases treated with salvage surgery for local progression from October 2002 to July 2019. These patients had undergone salvage surgery based on magnetic resonance imaging findings and/or clinical evidence of post-STI local progression and stable systemic disease. We employed two prospective strategies according to the eloquency of the lesions. Lesions in non-eloquent areas had been resected completely with a safety margin, utilizing a fence-post method; while lesions in eloquent areas had been treated with minimal resection and postoperative STI. Prognostic factors for survival were analyzed. RESULTS Fifty-four salvage surgeries had been performed on 48 patients. The median age of patients was 64 years. The median diameter of the enhanced lesions was 35 mm (range 19–58 mm). The median overall survival was 20.2 months from salvage surgery and 37.5 months from initial STI. Primary cancers were lung 31, breast 9, and others 8. Local recurrence developed in 13 of 54 lesions (24%). Leptomeningeal dissemination occurred after surgery in 3 patients (5.6%). Primary breast cancer (breast vs. lung: HR: 0.17), (breast vs. others: HR: 0.08) and RPA class 1–2 (RPA 1 vs. 3, HR: 0.13), (RPA 2 vs 3, HR: 0.4) were identified as good prognostic factors for overall survival (OS) in multivariate analyses. CONCLUSION We insist that salvage surgery leads to rapid improvement of neurological function and clarity of histological diagnosis. Salvage surgery is recommended for large lesions especially with surrounding edema either in eloquent or non-eloquent areas.

scholarly journals Retrospective analysis of salvage surgery for local progression of brain metastasis previously treated with stereotactic irradiation: diagnostic contribution, functional outcome, and prognostic factors

2020 ◽  
Author(s):  
Koichi Mitsuya ◽  
Yoko Nakasu ◽  
Shoichi Deguchi ◽  
Takuma Oishi ◽  
Takashi Sugino ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Brain Metastases ◽  
Salvage Surgery ◽  
Systemic Disease ◽  
Safety Margin ◽  
Rapid Improvement ◽  
Stereotactic Irradiation ◽  
Eloquent Areas ◽  
Local Progression

Abstract Background: Stereotactic irradiation (STI) is a primary treatment for patients with newly diagnosed brain metastases. Some of these patients experience local progression, which is difficult to differentiate from radiation necrosis, and difficult to treat. So far, just a few studies have clarified the prognosis and effectiveness of salvage surgery after STI. We evaluated the diagnostic value and improvement of functional outcomes after salvage surgery. Based on these results, we reconsidered surgical indication for patients with local progression after STI. Methods: We evaluated patients with brain metastases treated with salvage surgery for local progression from October 2002 to July 2019. These patients had undergone salvage surgery based on magnetic resonance imaging findings and/or clinical evidence of post-STI local progression and stable systemic disease. We employed two prospective strategies according to the eloquency of the lesions. Lesions in non-eloquent areas had been resected completely with a safety margin, utilizing a fence-post method; while lesions in eloquent areas had been treated with minimal resection and postoperative STI. Kaplan-Meier curves were used for the assessment of overall survival. Prognostic factors for survival were analyzed. Results: Fifty-four salvage surgeries had been performed on 48 patients. The median age of patients was 63.5 years (range 36-79). The median interval from STI to surgery was 12 months. The median overall survival was 20.2 months from salvage surgery and 37.5 months from initial STI. Primary cancers were lung 31, breast 9, and others 8. Local recurrence developed in 13 of 54 lesions (24%). Leptomeningeal dissemination occurred after surgery in 3 patients (5.6%). Primary breast cancer (breast vs. lung: HR: 0.17), (breast vs. others: HR: 0.08) and RPA class 1-2 (RPA 1 vs. 3, HR:0.13), (RPA 2 vs 3, HR:0.4) were identified as good prognostic factors for overall survival (OS) in multivariate analyses. The peripheral neutrophil-to-lymphocyte ratio (NLR) of ≤3.65 predicted significantly longer OS (median 25.5 months) than an NLR >3.65 (median 8 months). Conclusion: We insist that salvage surgery leads to rapid improvement of neurological function and clarity of histological diagnosis. Salvage surgery is recommended for large lesions especially with surrounding edema either in eloquent or non-eloquent areas.

scholarly journals Retrospective analysis of salvage surgery for local progression of brain metastasis previously treated with stereotactic irradiation: diagnostic benefit, functional outcome, and prognostic factors

2019 ◽  
Author(s):  
Koichi Mitsuya ◽  
Yoko Nakasu ◽  
Nakamasa Hayashi ◽  
Shoichi Deduchi ◽  
Takuma Oishi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Brain Metastases ◽  
Salvage Surgery ◽  
Systemic Disease ◽  
Safety Margin ◽  
Rapid Improvement ◽  
Stereotactic Irradiation ◽  
Eloquent Areas ◽  
Local Progression

Abstract BackgroundStereotactic irradiation (STI) is a primary treatment for patients with newly diagnosed brain metastases. Some of these patients experience local progression, which is difficult to differentiate from radiation necrosis, and difficult to treat. So far, just a few studies have clarified the prognosis and effectiveness of salvage surgery after STI. We evaluated the diagnostic value and improvement of functional outcomes after salvage surgery. Based on these results, we reconsidered surgical indication for patients with local progression after STI.MethodsWe evaluated patients with brain metastases treated with salvage surgery for local progression from October 2002 to July 2019. These patients had undergone salvage surgery based on magnetic resonance imaging findings and/or clinical evidence of post-STI local progression and stable systemic disease. We employed two prospective strategies according to the eloquency of the lesions. Lesions in non-eloquent areas had been resected completely with a safety margin, utilizing a fence-post method; while lesions in eloquent areas had been treated with minimal resection and postoperative STI. Kaplan-Meier curves were used for the assessment of overall survival. Prognostic factors for survival were analyzed.ResultsFifty-four salvage surgeries had been performed on 48 patients. The median age of patients was 63.5 years (range 36-79). The median interval from STI to surgery was 12 months. The median overall survival was 20.2 months from salvage surgery and 37.5 months from initial STI. Primary cancers were lung 31, breast 9, and others 8. Local recurrence developed in 13 of 54 lesions (24%). Leptomeningeal dissemination occurred after surgery in 3 patients (5.6%). Primary breast cancer (breast vs. lung: HR: 0.17), (breast vs. others: HR: 0.08) and RPA class 1-2 (RPA 1 vs. 3, HR:0.13), (RPA 2 vs 3, HR:0.4) were identified as good prognostic factors for overall survival (OS) in multivariate analyses. The peripheral neutrophil-to-lymphocyte ratio (NLR) of ≤3.65 predicted significantly longer OS (median 25.5 months) than an NLR >3.65 (median 8 months). ConclusionWe insist that salvage surgery leads to rapid improvement of neurological function and clarity of histological diagnosis. Salvage surgery is recommended for large lesions especially with surrounding edema either in eloquent or non-eloquent areas.

scholarly journals MET-01 INDICATION AND OUTCOME OF SALVAGE SURGERY FOR LOCAL PROGRESSION OF BRAIN METASTASIS PREVIOUSLY TREATED WITH STEREOTACTIC IRRADIATION

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii35-ii35
Author(s):  
Koichi Mitsuya ◽  
Shoichi Deguchi ◽  
Yoko Nakasu ◽  
Nakamasa Hayashi
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Brain Metastasis ◽  
Brain Metastases ◽  
Salvage Surgery ◽  
Primary Cancer ◽  
Stereotactic Irradiation ◽  
Meaningful Improvement ◽  
Local Progression ◽  
Clinical Records

Abstract PURPOSE To determine treatment outcome following salvage surgery (SS) for local progression of brain metastasis treated by stereotactic irradiation (STI). METHODS The clinical records of patients who underwent SS of local progression of brain metastases after STI at our institute between October 2002 and July 2019 were retrospectively reviewed. Kaplan-Meier curves were used for the assessment of overall survival (OS). The decision to perform SS was based on findings of magnetic resonance imaging and/or clinical evidence of local progression of the brain metastases and status of systemic disease. Prognostic factors for survival were analyzed; age, sex, primary cancer, RPA classification at surgery, extent of resection, radiotherapy after salvage surgery, and pre-surgical neutrophil-to-lymphocyte ratio (NLR). RESULTS Fifty-four SS of 48 patients were performed. The median age of the patients was 63 years (range 36–79). The median interval from STI to SS was 12 months. The median overall survival was 20.2 months from SS. Primary cancer were lung 34, breast 10, and other 10. Fourteen of 54 lesions (26%) developed local recurrence. Leptomeningeal dissemination occurred after the SS in 3 patients (5.7%). RPA classification (1 vs 3, HR:0.16, 95%CI: 0.03–0.59) (2 vs 3, HR:0.44, 95%CI:0.19–0.97) and primary cancer (breast vs lung, HR:0.21, 95%CI:0.05–0.64) (breast vs others, HR:0.08, 95%CI:0.015–0.32) (lung vs others, HR:0.38, 95%CI:0.16–0.94)) were identified as good prognostic factors of overall survival in multivariate analysis. The optimum NLR threshold value was identified as 3.65 for 1-year survival from SS (AUC0.62, sensitivity:71%). CONCLUSIONS Salvage surgery for local progression of brain metastases after STI in selected cases leads to a meaningful improvement in survival.

scholarly journals Hypofractionated and single-fraction radiosurgery for brain metastases with sex as a key predictor of overall survival

2020 ◽  
Author(s):  
Julian Mangesius ◽  
Seppi Thomas ◽  
Bates Katie ◽  
Christoph Reinhold Arnold ◽  
Minasch Danijela ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Brain Metastases ◽  
Proportional Hazards ◽  
Predictive Accuracy ◽  
Systemic Disease ◽  
Cox Proportional Hazards ◽  
Prognostic Scores ◽  
Single Fraction ◽  
Male Patients

Abstract Background: Overall survival (OS) of patients with brain metastases treated with hypofractionated (HFSRT) or single-fraction (SRS) radiosurgery depends on several prognostic factors. The aim of this study was to investigate the potential of sex as an independent predictor of OS and evaluate the predictive accuracy of common prognostic scores.Methods: Retrospective analysis of 281 consecutive patients receiving radiosurgery of brain metastases was performed. Kaplan-Meier survival curves and Cox proportional hazards models were used to compare OS between SRS and HFSRT and by sex, before and after propensity-score matching (PSM) on key baseline prognostic covariates. Prognostic scores were evaluated using Harrell’s concordance index.Results: Median OS was 11 months after both SRS and HFSRT. After PSM, median OS was 12 months after SRS (95%CI: 7.5-16.5) and 9 months after HFSRT (95%CI: 5.0-13.0; p=0.77). Independent prognostic factors were sex, primary tumor, KPI, and systemic disease status. Median OS was 16 months for women and 7 months for male patients (p<0.001). After excluding sex specific tumors, PSM revealed a median OS of 16 months for women and 8 months for male patients (p<0.01). Evaluation of prognostic indices showed BSBM to be the most accurate (Harrell’s C=0.68), followed by SIR (0.61), GPA (0.60), RPA (0.58), and Rades et al. (0.57).Conclusions: OS after HFSRT and SRS did not differ, although PSM revealed a non-significant advantage for SRS. Female sex was found to be a major independent positive prognostic factor for survival, and thus should be considered in the personalized decision-making of brain metastases treatment.

scholarly journals Hypofractionated and single-fraction radiosurgery for brain metastases with sex as a key predictor of overall survival

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Julian Mangesius ◽  
Thomas Seppi ◽  
Katie Bates ◽  
Christoph R. Arnold ◽  
Danijela Minasch ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Brain Metastases ◽  
Proportional Hazards ◽  
Predictive Accuracy ◽  
Systemic Disease ◽  
Cox Proportional Hazards ◽  
Prognostic Scores ◽  
Single Fraction ◽  
Male Patients

AbstractOverall survival (OS) of patients with brain metastases treated with hypofractionated (HFSRT) or single-fraction (SRS) radiosurgery depends on several prognostic factors. The aim of this study was to investigate the potential of sex as an independent predictor of OS and evaluate the predictive accuracy of common prognostic scores. Retrospective analysis of 281 consecutive patients receiving radiosurgery of brain metastases was performed. Kaplan–Meier survival curves and Cox proportional hazards models were used to compare OS between SRS and HFSRT and by sex, before and after propensity-score matching (PSM) on key baseline prognostic covariates. Prognostic scores were evaluated using Harrell’s concordance index. Median OS was 11 months after both SRS and HFSRT. After PSM, median OS was 12 months after SRS (95% CI: 7.5–16.5) and 9 months after HFSRT (95% CI: 5.0–13.0; p = 0.77). Independent prognostic factors were sex, primary tumor, KPI, and systemic disease status. Median OS was 16 months for women and 7 months for male patients (p < 0.001). After excluding sex specific tumors, PSM revealed a median OS of 16 months for women and 8 months for male patients (p < 0.01). Evaluation of prognostic indices showed BSBM to be the most accurate (Harrell’s C = 0.68), followed by SIR (0.61), GPA (0.60), RPA (0.58), and Rades et al. (0.57). OS after HFSRT and SRS did not differ, although PSM revealed a non-significant advantage for SRS. Female sex was found to be a major independent positive prognostic factor for survival, and thus should be considered in the personalized decision-making of brain metastases treatment.

scholarly journals TRLS-01. RADIOSURGERY FOLLOWED BY TUMOR TREATING FIELDS (TTFIELDS) FOR BRAIN METASTASES (1–10) FROM NSCLC IN THE PHASE 3 METIS TRIAL

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i8-i8
Author(s):  
Minesh Mehta ◽  
Vinai Gondi ◽  
Manmeet Ahluwalia ◽  
Paul Brown
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Electric Fields ◽  
Systemic Disease ◽  
Data Monitoring Committee ◽  
Rank Test ◽  
Progression Rate ◽  
Tumor Treating Fields ◽  
Nsclc Patients ◽  
The Brain

Abstract Tumor Treating Fields (TTFields) are non-invasive, loco-regional, anti-mitotic treatment comprising alternating electric fields that have demonstrated efficacy in preclinical non-small cell lung cancer (NSCLC) models. TTFields to the brain was safe and extended overall survival in newly-diagnosed glioblastoma. The METIS study [NCT02831959] investigates the efficacy and safety of TTFields in NSCLC patients with brain metastases. NSCLC patients (N=270) with 1–10 brain metastases are randomized 1:1 to stereotactic radio surgery (SRS) followed by continuous TTFields ((150 kHz, &gt; 18 hours/day) within 7 days of SRS or supportive care. The TTFields portable device delivers TTFields to the brain using 4 transducer arrays, while patients receive the best standard-of-care for their systemic disease. Patients are followed every two months until second intracranial progression. Key inclusion criteria: KPS ≥70, new diagnosis of 1 inoperable or 2–10 supra- and/or infratentorial brain metastases from NSCLC amenable to SRS; KPS ≥70; and optimal therapy for extracranial disease. Prior WBRT or surgical resection of metastases, a single resectable lesion or recurrent brain metastases were exclusionary. Primary endpoint was time to 1st intracranial progression. Secondary endpoints included time to neurocognitive failure (HVLT, COWAT and TMT), overall survival, radiological response rate (RANO-BM and RECIST V1.1); quality-of-life; adverse events; time to first/second intracranial progression for patients with 1–4 and 5–10 brain metastases; bi-monthly intracranial progression rate from 2–12 months; and time to second intracranial and distant progression. The sample size (N=270) was calculated using a log-rank test (Lakatos 1988 and 2002) with 80% power at a two sided alpha of 0.05 to detect a hazard ratio of 0.57. In August 2018, an independent Data Monitoring Committee (DMC) performed a review of the METIS trial data collected to that point. The DMC concluded that no unexpected safety issues have emerged on the study, and recommended to continue the METIS study as planned.

scholarly journals 30. RADIOSURGERY FOLLOWED BY TUMOR TREATING FIELDS FOR BRAIN METASTASES (1–10) FROM NSCLC IN THE PHASE 3 METIS TRIAL

2020 ◽  
Vol 2 (Supplement_2) ◽  
pp. ii5-ii5
Author(s):  
Minesh P Mehta ◽  
Vinai Gondi ◽  
Paul Brown ◽  
Manmeet Ahluwalia
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Electric Fields ◽  
Systemic Disease ◽  
Data Monitoring Committee ◽  
Rank Test ◽  
Progression Rate ◽  
Tumor Treating Fields ◽  
Nsclc Patients ◽  
The Brain

Abstract BACKGROUND Tumor Treating Fields (TTFields) are non-invasive, loco-regional, anti-mitotic treatment modality comprising alternating electric fields. TTFields have demonstrated efficacy in preclinical non-small cell lung cancer (NSCLC) models. TTFields treatment to the brain was safe and extended overall survival in newly-diagnosed glioblastoma. The objective of the METIS study [NCT02831959] is evaluation of the efficacy and safety of TTFields in NSCLC patients with brain metastases. METHODS NSCLC patients (N=270) with 1–10 brain metastases were randomized 1:1 to stereotactic radio surgery (SRS) followed by continuous TTFields ((150 kHz, &gt; 18 hours/day) within 7 days of SRS or supportive care. The portable device delivered TTFields to the brain using 4 transducer arrays, while patients received the best standard-of-care for systemic disease. Patients were followed every two months until second intracranial progression. Key inclusion criteria: KPS ≥70, new diagnosis of 1 inoperable or 2–10 supra- and/or infratentorial brain metastases from NSCLC amenable to SRS; and optimal therapy for extracranial disease. Prior WBRT, surgical resection of metastases, or recurrent brain metastases were exclusionary. Primary endpoint was time to 1st intracranial progression. Secondary endpoints included time to neurocognitive failure (HVLT, COWAT and TMT), overall survival, radiological response rate (RANO-BM and RECIST V1.1); quality-of-life; adverse events; time to first/second intracranial progression for patients with 1–4 and 5–10 brain metastases; bi-monthly intracranial progression rate from 2–12 months; and time to second intracranial and distant progression. The sample size (N=270) was calculated using a log-rank test (Lakatos 1988 and 2002) with 80% power at two sided alpha of 0.05 to detect a hazard ratio of 0.57. On September, 2019, an independent Data Monitoring Committee (DMC) reviewed METIS trial data collected to that point. The DMC concluded that no unexpected safety issues had emerged and recommended continuation of the METIS study as planned.

Evaluation of Prognostic Factors for Early Mortality After Stereotactic Radiosurgery for Brain Metastases: a Single Institutional Retrospective Review

Neurosurgery ◽  
2017 ◽  
Vol 83 (1) ◽  
pp. 128-136 ◽  
Author(s):  
E Emily Bennett ◽  
Michael A Vogelbaum ◽  
Gene H Barnett ◽  
Lilyana Angelov ◽  
Samuel Chao ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Karnofsky Performance Status ◽  
Systemic Disease ◽  
Performance Status ◽  
Early Death ◽  
Tumor Type ◽  
Prognostic Groups ◽  
Prior Surgery

Abstract BACKGROUND Stereotactic radiosurgery (SRS) is used commonly for patients with brain metastases (BM) to improve intracranial disease control. However, survival of these patients is often dictated by their systemic disease course. The value of SRS becomes less clear in patients with anticipated short survival. OBJECTIVE To evaluate prognostic factors, which may predict early death (within 90 d) after SRS. METHODS A total of 1427 patients with BM were treated with SRS at our institution (2000-2012). There were 1385 cases included in this study; 1057 patients underwent upfront SRS and 328 underwent salvage SRS. The primary endpoint of the study was all-cause mortality within 90 d after first SRS. Multivariate analyses were performed to develop prognostic indices. RESULTS Two hundred sixty-six patients (19%, 95% confidence interval 17%-21%) died within 90 d after SRS. Multivariate analysis of upfront SRS patients showed that Karnofsky Performance Status, primary tumor type, extracranial metastases, age at SRS, boost treatment, total tumor volume, prior surgery, and interval from primary to BM were independent prognostic factors for 90-d mortality. The first 4 factors were also independent predictors in patients treated with salvage SRS. Based on these factors, an index was defined for each group that categorized patients into 3 and 2 prognostic groups, respectively. Ninety-day mortality was 5% to 7% in the most favorable cohort and 36% to 39% in the least favorable. CONCLUSION Indices based on readily available patient, clinical, and treatment factors that are highly predictive of early death in patients treated with upfront or salvage SRS can be calculated and used to define well-separated prognostic groups.

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