Significant survival improvements for patients with melanoma brain metastases: can we reach cure in the current era?

Berger, Assaf; Bernstein, Kenneth; Alzate, Juan Diego; Mullen, Reed; Silverman, Joshua; Sulman, Erik P.; Donahue, Bernadine R.; Pavlick, Anna C.; Gurewitz, Jason; Mureb, Monica; Mehnert, Janice M.; Madden, Kathleen; Palermo, Amy; Weber, Jeffrey S.; Golfinos, John G.; Kondziolka, Douglas

doi:10.1007/s11060-022-04036-1

Cited by 9 publications

(6 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our radiosurgical technique has been described in detail in previous reports. 15,16 In brief, radiosurgery was performed using the Leksell Gamma Knife Perfexion or Icon ® model (Elekta). Follow-ups were scheduled 2 months after SRS and then at 3-month intervals for the first 2 years before the imaging interval was lengthened if no new tumors were seen.…”

Section: Radiosurgery Proceduresmentioning

confidence: 99%

“…31 In this work, we defined 5 years from initial SRS as the cutoff of long-term survival. 15,16 Among studies of BCBM of mixed subtypes, the long-term survival at 5 years has varied from 0% to 5%. [32][33][34] In our study, 17% of patients with a follow-up of 5 years met that criterion, most frequently, patients with the HR+/HER2+ subtype.…”

Section: Overall and Long-term Survivalmentioning

confidence: 99%

See 1 more Smart Citation

Long-term Survival From Breast Cancer Brain Metastases in the Era of Modern Systemic Therapies

et al. 2023

Self Cite

View full text Add to dashboard Cite

BACKGROUND AND OBJECTIVES: Median survival for all patients with breast cancer with brain metastases (BCBMs) has increased in the era of targeted therapy (TT) and with improved local control of intracranial tumors using stereotactic radiosurgery (SRS) and surgical resection. However, detailed characterization of the patients with long-term survival in the past 5 years remains sparse. The aim of this article is to characterize patients with BCBM who achieved long-term survival and identify factors associated with the uniquely better outcomes and to find predictors of mortality for patients with BCBM. METHODS: We reviewed 190 patients with breast cancer with 931 brain tumors receiving SRS who were followed at our institution with prospective data collection between 2012 and 2022. We analyzed clinical, molecular, and imaging data to assess relationship to outcomes and tumor control. RESULTS: The median overall survival from initial SRS and from breast cancer diagnosis was 25 months (95% CI 19-31 months) and 130 months (95% CI 100-160 months), respectively. Sixteen patients (17%) achieved long-term survival (survival ≥5 years from SRS), 9 of whom are still alive. Predictors of long-term survival included HER2+ status (P = .041) and treatment with TT (P = .046). A limited number of patients (11%) died of central nervous system (CNS) causes. A predictor of CNS-related death was the development of leptomeningeal disease after SRS (P = .025), whereas predictors of non-CNS death included extracranial metastases at first SRS (P = .017), triple-negative breast cancer (P = .002), a Karnofsky Performance Status of <80 at first SRS (P = .002), and active systemic disease at last follow-up (P = .001). Only 13% of patients eventually needed whole brain radiotherapy. Among the long-term survivors, none died of CNS progression. CONCLUSION: Patients with BCBM can achieve long-term survival. The use of TT and HER2+ disease are associated with long-term survival. The primary cause of death was extracranial disease progression, and none of the patients living ≥5 years died of CNS-related disease.

show abstract

Section: Radiosurgery Proceduresmentioning

confidence: 99%

Section: Overall and Long-term Survivalmentioning

confidence: 99%

Long-term Survival From Breast Cancer Brain Metastases in the Era of Modern Systemic Therapies

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“… 76 Importantly, patients with BRAF mutations are at a higher risk of BM incidence and approximately 29%–56% of melanoma patients with BM have BRAF mutations in their primary tumors. 52 , 77 , 78 In particular, melanomas with BRAF -V600 mutations have an increased risk of BM and it is estimated that BRAF -V600 is found in approximately 14% of melanoma BM. 78 Importantly, patients with BRAF mutations have longer median survival than those without, likely due to targeted therapies against BRAF -mutant melanoma with excellent CNS penetration and immune checkpoint inhibitors.…”

Section: Epidemiology Molecular Characterization and Screening Guidel...mentioning

confidence: 99%

Brain metastasis screening in the molecular age

Tabor

Onoichenco

Narayan

et al. 2023

Neuro-Oncology Advances

View full text Add to dashboard Cite

The incidence of brain metastases (BM) amongst cancer patients has been increasing due to improvements in therapeutic options and an increase in overall survival. Molecular characterization of tumors has provided insights into the biology and oncogenic drivers of BM and molecular subtype-based screening. Though there are currently some screening and surveillance guidelines for BM, they remain limited. In this comprehensive review, we review and present epidemiological data on BM, their molecular characterization, and current screening guidelines. The molecular subtypes with the highest BM incidence are EGFR-mutated NSCLC, BRCA1, TN, and HER2+ breast cancers, and BRAF-mutated melanoma. Furthermore, BMs are more likely to present asymptomatically at diagnosis in oncogene-addicted NSCLC and BRAF-mutated melanoma. European screening standards recommend more frequent screening for oncogene-addicted NSCLC patients, and clinical trials are investigating screening for BM in HR+, HER2+, and TN breast cancers. However, more work is needed to determine optimal screening guidelines for other primary cancer molecular subtypes. With the advent of personalized medicine, molecular characterization of tumors has revolutionized the landscape of cancer treatment and prognostication. Incorporating molecular characterization into BM screening guidelines may allow physicians to better identify patients at high risk for BM development and improve patient outcomes.

show abstract

“…Conformal stereotactic radiosurgery (SRS) achieves similar local control to whole-brain radiation therapy with fewer cognitive adverse effects and better quality of life . With the introduction of precision targeted cancer therapies and immune checkpoint inhibitors, survival rates for patients with BrMs have improved significantly . These advances have brought the objective of minimizing toxic effects while achieving long-term local control of BrM to the forefront of treatment priorities.…”

Section: Introductionmentioning

confidence: 99%

“… 4 , 5 With the introduction of precision targeted cancer therapies and immune checkpoint inhibitors, survival rates for patients with BrMs have improved significantly. 6 , 7 , 8 , 9 , 10 These advances have brought the objective of minimizing toxic effects while achieving long-term local control of BrM to the forefront of treatment priorities.…”

Section: Introductionmentioning

confidence: 99%

Outcomes Following Early Postoperative Adjuvant Radiosurgery for Brain Metastases

Bander,

El Ahmadieh,

Chen

et al. 2023

JAMA Netw Open

View full text Add to dashboard Cite

ImportanceAdjuvant stereotactic radiosurgery (SRS) enhances the local control of resected brain metastases (BrM). However, the risks of local failure (LF) and potential for posttreatment adverse radiation effects (PTRE) after early postoperative adjuvant SRS have not yet been established.ObjectiveTo evaluate whether adjuvant SRS delivered within a median of 14 days after surgery is associated with improved LF without a concomitant increase in PTRE.Design, Setting, and ParticipantsThis prospective cohort study examines a clinical workflow (RapidRT) that was implemented from 2019 to 2022 to deliver SRS to surgical patients within a median of 14 days, ensuring all patients were treated within 30 days postoperatively. This prospective cohort was compared with a historical cohort (StanRT) of patients with BrM resected between 2013 and 2019 to assess the association of the RapidRT workflow with LF and PTRE. The 2 cohorts were combined to identify optimal SRS timing, with a median follow-up of 3.3 years for survivors.ExposureTiming of adjuvant SRS (14, 21, and 30 days postoperatively).Main Outcomes and MeasuresLF and PTRE, according to modified Response Assessment in Neuro-Oncology Brain Metastases criteria.ResultsThere were 438 patients (265 [60.5%] female patients; 23 [5.3%] Asian, 27 [6.2%] Black, and 364 [83.1%] White patients) with a mean (SD) age of 62 (13) years; 377 were in the StanRT cohort and 61 in the RapidRT cohort. LF and PTRE rates at 1 year were not significantly different between RapidRT and StanRT cohorts. Timing of SRS was associated with radiographic PTRE. Patients receiving radiation within 14 days had the highest 1-year PTRE rate (18.08%; 95% CI, 8.31%-30.86%), and patients receiving radiation between 22 and 30 days had the lowest 1-year PTRE rate (4.10%; 95% CI, 1.52%-8.73%; P = .03). LF rates were highest for patients receiving radiation more than 30 days from surgery (10.65%; 95% CI, 6.90%-15.32%) but comparable for patients receiving radiation within 14 days, between 15 and 21 days, and between 22 and 30 days (≤14 days: 5.12%; 95% CI, 0.86%-15.60%; 15 to ≤21 days: 3.21%; 95% CI, 0.59%-9.99%; 22 to ≤30 days: 6.58%; 95% CI, 3.06%-11.94%; P = .20).Conclusions and RelevanceIn this cohort study of adjuvant SRS timing following surgical resection of BrM, the optimal timing for adjuvant SRS appears to be within 22 to 30 days following surgery. The findings of this study suggest that this timing allows for a balanced approach that minimizes the risks associated with LF and PTRE.

show abstract

Significant survival improvements for patients with melanoma brain metastases: can we reach cure in the current era?

Cited by 9 publications

References 52 publications

Long-term Survival From Breast Cancer Brain Metastases in the Era of Modern Systemic Therapies

Long-term Survival From Breast Cancer Brain Metastases in the Era of Modern Systemic Therapies

Brain metastasis screening in the molecular age

Outcomes Following Early Postoperative Adjuvant Radiosurgery for Brain Metastases

Contact Info

Product

Resources

About