Extracranial Disease Status Research Articles

Multidisciplinary management strategies for recurrent brain metastasis after prior radiotherapy: An overview.

As cancer patients with intracranial metastatic disease experience increasingly prolonged survival, the diagnosis and management of recurrent brain metastasis pose significant challenges in clinical practice. Prior to deciding upon a management strategy, it is necessary to ascertain whether patients have recurrent/progressive disease vs adverse radiation effect, classify the recurrence as local or distant in the brain, evaluate the extent of intracranial disease (size, number and location of lesions, and brain metastasis velocity), the status of extracranial disease, and enumerate the interval from the last intracranially directed intervention to disease recurrence. A spectrum of salvage local treatment options includes surgery (resection and laser interstitial thermal therapy [LITT]) with or without adjuvant radiotherapy in the forms of external beam radiotherapy, intraoperative radiotherapy, or brachytherapy. Nonoperative salvage local treatments also range from single fraction and fractionated stereotactic radiosurgery (SRS/FSRS) to whole brain radiation therapy (WBRT). Optimal integration of systemic therapies, preferably with central nervous system (CNS) activity, may also require reinterrogation of brain metastasis tissue to identify actionable molecular alterations specific to intracranial progressive disease. Ultimately, the selection of the appropriate management approach necessitates a sophisticated understanding of patient, tumor, and prior treatment-related factors and is often multimodal; hence, interdisciplinary evaluation for such patients is indispensable.

Role of microsurgical tumor burden reduction in patients with breast cancer brain metastases considering molecular subtypes: a two-center volumetric survival analysis

BackgroundAdvancements in metastatic breast cancer (BC) treatment have enhanced overall survival (OS), leading to increased rates of brain metastases (BM). This study analyzes the association between microsurgical tumor reduction and OS in patients with BCBM, considering tumor molecular subtypes and perioperative treatment approaches.MethodsRetrospective analysis of surgically treated patients with BCBM from two tertiary brain tumor Swiss centers. The association of extent of resection (EOR), gross-total resection (GTR) achievement, and postoperative residual tumor volume (RV) with OS and intracranial progression-free survival (IC-PFS) was evaluated using Cox proportional hazard model.Results101 patients were included in the final analysis, most patients (38%) exhibited HER2-/HR + BC molecular subtype, followed by HER2 + /HR + (25%), HER2-/HR- (21%), and HER2 + /HR- subtypes (13%). The majority received postoperative systemic treatment (75%) and radiotherapy (84%). Median OS and intracranial PFS were 22 and 8 months, respectively. The mean pre-surgery intracranial tumor volume was 26 cm3, reduced to 3 cm3 post-surgery. EOR, GTR achievement and RV were not significantly associated with OS or IC-PFS, but higher EOR and lower RV correlated with extended OS in patients without extracranial metastases. HER2-positive tumor status was associated with longer OS, extracranial metastases at BM diagnosis and symptomatic lesions with shorter OS and IC-PFS.ConclusionsOur study found that BC molecular subtypes, extracranial disease status, and BM-related symptoms were associated with OS in surgically treated patients with BCBM. Additionally, while extensive resection to minimize residual tumor volume did not significantly affect OS across the entire cohort, it appeared beneficial for patients without extracranial metastases.

Radiosurgery to 5 or more newly diagnosed brain metastases in the systemic therapy era.

2026 Background: Stereotactic radiosurgery (SRS) is an ablative modality for focal treatment of brain metastases (BM) and is standard of care for limited BM. Suitability for SRS has historically been linked to number of BM, with up to 4 BM considered amenable to SRS. JLGK0901 revealed no difference in overall survival (OS) and similar rates of adverse events for patients with 5-10 vs. 2-4 BM. Evidence supporting for SRS for >10 BM is limited. As systemic treatments have evolved to include agents with improved central nervous system (CNS) efficacy and OS, the role of SRS warrants re-evaluation. Methods: We retrospectively reviewed patients from a single institution with ≥5 BM treated with SRS with no prior history of brain radiation 2015-2022 on an IRB-approved protocol. Clinical history, including sex, histology, Karnofsky performance status (KPS), extracranial disease status and systemic regimen used before and after diagnosis of BM, was reviewed. Systemic regimens were categorized based on potential for CNS efficacy as 1) none: no evidence, 2) weak: single agent immunotherapy or known but limited data on CNS efficacy, or 3) strong: multiple agents with known CNS efficacy, single agents with strong CNS efficacy. Kaplan-Meier method was used to estimate survival with log-rank test used to evaluate differences in survival curves. Cox proportional hazards modeling was used to evaluate differences in CNS progression-free survival (CNS-PFS) and OS. Results: 558 patients (48% female) who received SRS to ≥5 BM (range 5-23) were identified. Primary histologies included: 36% non-small cell lung cancer; 22% melanoma; 14% breast; 7% renal; 5% gastrointestinal; 15% other. Median OS was 11.0 months and did not differ between patients with 5-9 (n=441) vs ≥10 BM (n=117) (median OS 11.1 vs. 10.0 months; p=0.53). Median CNS-PFS was 6.6 months and did not differ between 5-9 vs ≥ 10 BM (median CNS-PFS 6.4 vs. 7.7 p=0.86). On univariate analysis, high KPS (HR 0.96; p<0.001) was associated with improved OS. Histology ( p=0.14), BM number ( p=0.53); average BM volume ( p=0.48), and systemic disease status ( p=0.17) were not associated with OS. Change of systemic therapy at time of SRS was associated with improved OS (HR 0.58; p<0.001) and CNS-PFS (HR 0.63; p<0.001). Amongst patients with systemic therapy change, regimens with increased CNS efficacy compared to prior therapy were associated with improved OS (HR 0.59; p<0.001) and CNS-PFS (HR 0.65; p=0.002). Conclusions: In this large, retrospective analysis of patients with ≥ 5 previously untreated BM treated with SRS, we found no association between BM number and CNS-PFS or OS. Change in systemic therapy, particularly to agents with CNS efficacy, was associated with improved outcomes. While limited by biases inherent to retrospective analyses, these results suggest patients with larger number of BM (≥10) are appropriate for SRS, especially when changing to systemic therapy with CNS penetrance.

Exploration of radiotherapy strategy for brain metastasis patients with driver gene positivity in lung cancer.

Objective: To assess the disparities in effectiveness and identify outcome predictors in the treatment of a targeted-first and radiotherapy-first regimen with driver gene-positive lung cancer brain metastases. Materials and Methods: This retrospective study analyzed patients with driver gene-positive lung cancer brain metastases who received first-targeted and first-radiotherapy regimens, respectively, with SIB-WBRT (whole brain tissue 40 Gy/20 fractions, tumor tissue boosted to 56-60 Gy/20 fractions) and local irradiation (prescription dose range of 20-60 Gy/2-25 fractions, most commonly delivered as 30 Gy/5 fractions, with a BED range of 28-100.8 Gy) at Peking Union Medical College Hospital from September 2015 to December 2021. The primary endpoint was intracranial progression free survival (iPFS). Secondary endpoints included overall survival (OS), intracranial new lesions, and tumor control. The Kaplan-Meier method was utilized to depict and estimate iPFS, OS, intracranial new lesions and tumor control. The Cox regression analysis was conducted to assess the association between relevant factors and outcomes. Results: 88 patients were enrolled in targeted-first and radiotherapy-first regimen, totally. And no difference was found in the comparison of iPFS between the two groups (HR=1.180, 95%CI: 0.622-2.237, P=0.613). No difference was found in the comparison of OS between the two groups (HR=1.208, 95%CI: 0.679-2.150, P=0.520). No difference was found in the comparison of intracranial new lesions between the two groups (HR=1.184, 95%CI: 0.569-2.463, P=0.652). There was a difference in the local control time between the two groups, with radiotherapy-first regimen being superior (HR=2.397, 95% CI:1.453-3.954, P<0.001). Patient age (HR=1.054, 95%CI: 1.026- 1.082, P<0.001), radiotherapy modality (HR=0.128, 95%CI: 0.041-0.401, P<0.001), metastasis volume (HR=1.426, 95%CI: 1.209-1.682, P<0.001), number of metastases(HR=14.960, 95%CI: 1.990-112.444, P=0.009), extracranial disease status (HR=0.387, 95%CI: 0.170-0.880, P=0.023) and therapy sequence (HR=13.800, 95%CI: 4.455-42.751, P<0.001) were associated with local control. Conclusion: Targeted-first regimen was not found to improve patients' iPFS relative to radiotherapy-first regimen in patients with brain metastases. Radiotherapy-first regimen for brain metastases demonstrated superior local control compared to targeted-first regimen. Patient's age, radiotherapy modality, metastasis volume, number of metastases, extracranial disease status and therapy sequence may be related to local control of metastases.

Brain Metastases in the Setting of Stable Versus Progressing Extracranial Disease Among Patients With Metastatic Breast Cancer

IntroductionWomen with metastatic breast cancer (BC) are at risk of developing brain metastases (BrM), which may result in significant morbidity and mortality. Given the emergence of systemic therapies with activity in the brain, more breast oncology clinical trials include patients with BrM, but most require extracranial disease progression for trial participation. MethodsWe evaluated the proportion of patients with BC BrM who have intracranial disease progression in the setting of stable extracranial disease in a retrospective cohort study of 751 patients treated between 2008 and 2018 at the Sunnybrook Odette Cancer. Extracranial disease progression was defined as any progression outside of the brain within 4 weeks of a patient's local/regional treatment. Clinical/pathologic characteristics and outcomes were also abstracted from patients’ medical records. ResultsOf 752 patients in the cohort, 691 were included in our study. Sixty-one patients were excluded due to the presence of a second primary tumor or uncertain tissue origin of the BrM. BC subtype based on the primary tumor was known for 592 (85.6%) patients; 33.1% (n = 196) had HER2+ disease, 40% (n = 237) had HR+/HER2- disease, and 26.9% (n = 159) had triple negative BC. Extracranial disease status was available for 677 patients (98%); 41.1% (n = 284/691) had stable extracranial disease and 56.8% (n = 393/691) had extracranial disease progression within 4 weeks of treatment for BrM. DiscussionA high proportion of patients with BC BrM (41.1%) would be excluded from clinical trials due to stable extracranial disease. Efforts should be made to design trials for this patient population.

Toxicity and outcomes of melanoma brain metastases treated with stereotactic radiosurgery: the risk of subsequent symptomatic intralesional hemorrhage exceeds that of radiation necrosis.

We aimed to assess the outcomes and patterns of toxicity in patients with melanoma brain metastases (MBM) treated with stereotactic radiosurgery (SRS) with or without immunotherapy (IO). From a prospective registry, we reviewed MBM patients treated with single fraction Gamma Knife SRS between 2008 and 2021 at our center. We recorded all systemic therapies (chemotherapy, targeted therapy, or immunotherapy) administered before, during, or after SRS. Patients with prior brain surgery were excluded. We captured adverse events following SRS, including intralesional hemorrhage (IH), radiation necrosis (RN) and local failure (LF), as well as extracranial disease status. Distant brain failure (DBF), extracranial progression-free survival (PFS) and overall survival (OS) were determined using a cumulative Incidence function and the Kaplan-Meier method. Our analysis included 165 patients with 570 SRS-treated MBM. Median OS for patients who received IO was 1.41 years versus 0.79 years in patients who did not (p = 0.04). Ipilimumab monotherapy was the most frequent IO regimen (30%). In the absence of IO, the cumulative incidence of symptomatic (grade 2 +) RN was 3% at 24 months and remained unchanged with respect to the type or timing of IO. The incidence of post-SRS g2 + IH in patients who did not receive systemic therapy was 19% at 1- and 2 years compared to 7% at 1- and 2 years among patients who did (HR: 0.33, 95% CI 0.11-0.98; p = 0.046). Overall, neither timing nor type of IO correlated to rates of DBF, OS, or LF. Among patients treated with IO, the median time to extracranial PFS was 5.4 months (95% IC 3.2 - 9.1). The risk of g2 + IH exceeds that of g2 + RN in MBM patients undergoing SRS, with or without IO. IH should be considered a critical adverse event following MBM treatments.

Leptomeningeal metastasis in patients with non-small cell lung cancer after stereotactic radiosurgery for brain metastasis.

Stereotactic radiosurgery (SRS) is an effective treatment for brain metastases (BMs) in patients with non-small cell lung cancer (NSCLC). However, factors associated with the development of post-SRS leptomeningeal metastasis (LM) remain unclear. The authors analyzed the incidence and risk factors of LM development in patients with NSCLC and BMs after SRS and examined the survival outcomes and prognostic factors after LM development. This retrospective study included patients with NSCLC treated with SRS for MRI-diagnosed BM from 2002 to 2021. The authors recorded various clinical and demographic data, including age, sex, tumor histology, molecular profile of tumors, extracranial disease status, previous craniotomy, Karnofsky Performance Status, systemic treatments, tumor volume, and number of BMs. The management and survival outcomes after LM diagnosis were also recorded. LM developed in 13.7% of patients with NSCLC and BMs after SRS treatment. Large initial tumor volume and more than 5 BM lesions, but not EGFR mutation status and post-SRS treatment, were associated with LM development after SRS. Multivariate analysis revealed that chemotherapy and targeted therapy after LM were associated with better survival in patients with LM after SRS. This study is the first to evaluate the risk factors for LM in a relatively large cohort of patients with NSCLC after SRS. In patients with BMs harboring risk factors for subsequent LM, such as initial tumor volume and number of metastatic lesions, aggressive therapies with high CNS penetrating ability should be considered.

CtDNA detection in patients with brain metastases arising from solid tumors.

2027 Background: While circulating tumor DNA (ctDNA) is a routine tool for therapeutics in metastatic solid tumors, data in those with stable and active brain metastases (BrMs) is limited. We assessed genomic alterations in ctDNA from patients (pts) with solid tumor BrMs in three groups: isolated BrMs/stable extracranial disease (iCNS), concurrent brain and extracranial progression (cCNS), and extracranial progression with no active BrMs at ctDNA draw (eCNS). We also compared ctDNA alterations between pts with and without BrMs. Methods: Pts with BrMs and a Guardant 360 profile (n=253) from the Duke Molecular Registry of Tumors between 01/2014 – 12/2020 were identified. Intracranial and extracranial disease status were determined via investigator assessment (RECIST and RANO-BM criteria) within 30 days of ctDNA test. Mutant allele fraction (MAF) was defined as the % of mutant alleles divided by total alleles at a given loci. Differences in mean ranks of the MAF % maximum were compared using the Kruskal-Wallis test and pairwise comparisons with the Dwass, Steel, Critchlow-Fligner multiple comparisons post-hoc procedure. We compared differences in MAF &gt;1% using the chi-square test. Results: Among the 253 pts with BrMs: 29 (12%) had iCNS, 160 (63%) cCNS, and 64 (25%) eCNS. The two most common tumor types were breast (BC, 12.0%) and non-small cell lung cancer (NSCLC, 76.4%). Median MAF was lower in the iCNS group (1.6%) vs cCNS (4.8%) p=0.002, but eCNS did not differ (2.6%). In pts with BC BrMs, ESR1 mutations were most frequent in the iCNS group (67%), followed cCNS (54%) then eCNS (18%) (p = 0.09) as were PIK3CA mutations, iCNS(50%), cCNS (46%), and eCNS (27%), p = 0.55. In pts with NSCLC BrMs, EGFR mutations were most frequent in the iCNS followed by cCNS then eCNS (67%, 40% and 37%, p = 0.08). KRAS mutations were more frequent in cCNS followed by eCNS and iCNS (30%, 17% and 6% p = 0.031). Patients with no BrMs (n=449) included 24% breast and 76% NSCLC. In the ctDNA, ESR1 and BRCA2 mutations were more frequent in pts with BC BrMs than those without (60% vs 25%, p&lt; 0.001) and (17% vs 5%, p=0.022), respectively. Mutations in EGFR were more frequent in pts with BrMs vs without (36% vs 17%, p&lt;0.001). Sequencing from both BrMs tissue and ctDNA were available for 8 pts (4cCNS and 4 iCNS). 7 of these (87.5%) had identical mutations in tumor and ctDNA. Conclusions: This study illustrates the feasibility of detecting actionable mutations from ctDNA among pts with BrMs, with and without extracranial disease. A higher frequency of actionable mutations in several targetable genes was observed in ctDNA when comparing pts with and without BrMs, thus providing therapeutic opportunities. Additional studies comparing ctDNA and alterations in BrMs tissue are needed to determine if ctDNA can be considered a surrogate to support treatment decisions.

Effect and safety of combining bevacizumab and fractionated stereotactic radiotherapy for brain metastases in patients with non-small cell lung cancer: A phase II trial.

e21132 Background: W e aimed to assess the efficacy and safety of c ombining b evacizumab and fractionated stereotactic radiotherapy ( FSRT ) for brain metastases (BMs) in non-small cell lung cancer ( NSCLC ) patients with stable extracranial disease status in this study. Methods: NSCLC patients with BMs were recruited between J anuary 20 20 and J anuary 202 2 . P atients were assigned to receive FSRT of 40Gy in 10 fractions (BED 56eGy) or 30Gy in 5 fractions (BED 48eGy). Meanwhile, bevacizumab was administered before FSRT (d1) and after FSRT (d21) with a dosage of 7.5mg/Kg. The primary endpoint of the study is intra-cranial progression-free survival (IPFS) . The secondary endpoints contained overall survival (OS), progression-free survival (PFS) , quality of life (QOL) score and toxicities. All time-to-event endpoints (IPFS, OS and PFS) were measured from the end of radiotherapy. Results: From J anuary 2020 and J anuary 202 2, 108 patients were recruited with a median follow-up duration was 15.2 months . The 1-year IPFS and OS rate were 82.9% ( 95% confidence interval (CI), 79.6%-86.2% ) and 80.4% ( 95% CI, 76.8%-84.0% ), respectively . The median PFS was 15.0 months ( 95% CI, 9.50-20.50 months ). The median IPFS and OS had not been reached at the time of the last follow-up. The treatment-related toxicities were mild with low incidence. Reversible mild hypertension and cerebral radio-necrosis were observed in 2 and 1 patients, respectively. No signs of ex tra-lesional haemorrhage and progression of peri-lesional oedema was found during the assessment period of treatment response. More importantly, significant improvent of QOL was observed in symptomatic patients. Conclusions: The combination of FSRT with bevacizumab in patients with NSCLC was well tolerated and achieved promising intracranial disease control. Patients maintained satisfactory QOL after receiving the combined regimen with low incidence of cerebral radio-necrosis. Clinical trial information: NCT04345146 .

Stereotactic Radiation Therapy for Brain Metastases: Factors Affecting Outcomes and Radiation Necrosis

Stereotactic radiation therapy (SRT) is a proven effective treatment for brain metastases (BM); however, symptomatic radiation necrosis (RN) is a late effect that may impact on patient's quality of life. The aim of our study was to retrospectively evaluate survival outcomes and characterize the occurrence of RN in a cohort of BM patients treated with ablative SRT at Federico II University Hospital. Clinical and dosimetric factors of 87 patients bearing a total of 220 BMs treated with SRT from 2016 to 2022 were analyzed. Among them, 46 patients with 127 BMs having clinical and MRI follow-up (FUP) ≥ 6 months were selected for RN evaluation. Dosimetric parameters of the uninvolved brain (brain without GTV) were extracted. The crude local control was 91% with neither clinical factors nor prescription dose correlating with local failure (LF). At a median FUP of 9 (1-68) months, the estimated median overall survival (OS), progression-free survival (PFS), and brain progression-free survival (bPFS) were 16, 6, and 9 months, respectively. The estimated OS rates at 1 and 3 years were 59.8% and 18.3%, respectively; bPFS at 1 and 3 years was 29.9% and 13.5%, respectively; PFS at 1 and 3 years was 15.7% and 0%, respectively; and local failure-free survival (LFFS) at 1 and 3 years was 87.2% and 83.8%, respectively. Extracranial disease status was an independent factor related to OS. Fourteen (30%) patients manifested RN. At multivariate analysis, adenocarcinoma histology, left location, and absence of chemotherapy were confirmed as independent risk factors for any-grade RN. Nine (20%) patients developed symptomatic (G2) RN, which improved or stabilized after 1-16 months of steroid therapy. With prompt recognition and, when necessary, medical therapy, RN radiological and clinical amelioration can be obtained.

Local treatment of breast cancer brain metastases

Breast cancer, along with lung cancer and melanoma, is one of the most common origins of central nervous system metastases. Due to improvement of systemic therapy options for primary disease and consequential prolonged survival, treatment of brain metastasis (BM) is presenting an evolving challenge. While new systemic therapy approaches for breast cancer brain metastasis are focusing on overcoming the blood brain and blood tumor barrier, as well as targeted therapies, local therapy remains the primary line of treatment. The decision of which local therapies to use, depends upon the number and volume of BM, their localization, patient’s clinical status, previously used treatments, status of extracranial disease and patient’s prognosis. In cases when an active approach, including surgery and/or radiotherapy, does not bring benefit to the patient’s quality of life or overall survival, best supportive care is recommended.

Prognostic factors for overall survival and intracranial progression in patients with renal cancer metastasis into the brain after neurosurgical treatment

Introduction. Treatment of patients with brain metastases is an important problem that should be considered in the framework of combination approach. Introduction of new techniques of drug therapy as well as radiotherapy and neurosurgical treatment allows to significantly increase patient survival. Effective drug therapy and local control of brain metastases are of utmost importance in prediction of overall survival and patient quality of life.Aim. To investigate the prognostic factors for overall survival and intracranial progression (local recurrences, distant metastases) in patients with brain metastases of renal cancer after neurosurgical resection.Materials and methods. Retrospective analysis of the treatment results of 114 patients with metastatic brain lesions due to renal cancer who underwent neurosurgical resection (NSR) at the N. N. Blokhin National medical Research Center of Oncology was performed. Clinical data of 102 (89.5 %) of 114 patients for whom data on survival was available were evaluated. Among them, 80 (78.4 %) of patients died, 22 (21.5 %) are under observation. Extracranial disease status at the time of NSR was known in 82 (71.9 %) patients: 45 (54.8 %) patients had extracranial metastases, and 37 (45.1 %) did not. Total resection of brain metastases with perifocal and perivascular zones was performed in 92 (90.1 %) patients; in other cases, fragmental lesion resection was performed.Results. median overall survival after NSR was 13.8 months (95 % confidence interval 10.3–18.6). per study data, factors affecting overall survival of patients with brain metastases of renal cancer after neurosurgical resection were presence / absence of extracranial metastases and patient’s functional status. Local recurrences in the postoperative cavity after NSR were observed in 24 (21 %) of 114 patients. median time of local recurrence was not achieved. Statistically significant factor of high risk of recurrence in the postoperative cavity was presence of lesions with maximal diameter ≥2 cm. Development of new (distant) metastases was observed in 31 (27.2 %) of 114 patients. median survival without distant metastases in patients with brain metastases after NSR was not achieved. frequencies of distant metastases at 6, 12 and 24 months were 15.5; 24.1 and 35.8 % respectively. per multifactor analysis, factors affecting development of distant metastases in the brain after NSR are multiple metastatic brain lesions and presence of extracranial metastases.Conclusion. Neurosurgical resection in patients with cerebral metastases of renal cancer in the total group leads to median overall survival of 13.8 months. predictors of better overall survival are absence of extracranial metastases and high functional status.

Brain metastasis as the first and only metastatic relapse site portends worse survival in patients with advanced HER2 + breast cancer.

Current systemic therapy guidelines for patients with HER2 + breast cancer brain metastases (BCBrM) diverge based on the status of extracranial disease (ECD). An in-depth understanding of the impact of ECD on outcomes in HER2 + BCBrM has never been performed. Our study explores the implications of ECD status on intracranial progression-free survival (iPFS) and overall survival (OS) after first incidence of HER2 + BCBrM and radiation. A retrospective analysis was performed of 151 patients diagnosed with initial HER2 + BCBrM who received radiation therapy to the central nervous system (CNS) at Duke between 2008 and 2021. The primary endpoint was iPFS defined as the time from first CNS radiation treatment to intracranial progression or death. OS was defined as the time from first CNS radiation or first metastatic disease to death. Systemic staging scans within 30days of initial BCBrM defined ECD status as progressive, stable/responding or none (isolated brain relapse). In this cohort, > 70% of patients had controlled ECD with either isolated brain relapse (27%) or stable/responding ECD (44%). OS from initial metastatic disease to death was markedly worse for patients with isolated intracranial relapse (median = 28.4m) compared to those with progressive or stable/responding ECD (48.8m and 71.5m, respectively, p = 0.0028). OS from first CNS radiation to death was significantly worse for patients with progressive ECD (16.9m) versus stable/responding (36.6m) or isolated intracranial relapse (28.4m, p = 0.007). iPFS did not differ statistically based on ECD status. Receipt of systemic therapy after first BCBrM significantly improved iPFS (HR 0.45, 95% CI: 0.25-0.81, p = 0.008) and OS (HR: 0.43 (95% CI: 0.23-0.81); p = 0.001). OS in patients with HER2 + isolated BCBrM was inferior to those with concurrent progressive or stable/responding ECD. Studies investigating initiation of brain-penetrable HER2-targeted therapies earlier in the disease course of isolated HER2 + intracranial relapse patients are warranted.

Survival and Prognostic Factors in Brain Metastases from Breast Cancer Treated with Stereotactic Radiotherapy

Abstract AIMS Intracranial metastases are common in patients with breast cancer. Stereotactic radiotherapy (SRT) can improve overall survival (OS) in selected patients; however there is uncertainty over the presence of prognostic indicators in this cohort. Here, we aim to determine whether the number of brain metastases, receptor status and presence of extracranial disease affected OS. METHOD Retrospective analysis was performed for all patients receiving SRT for brain metastases from breast cancer between 2014-2020 at Barts Cancer Centre. Overall survival (OS) was calculated using the Kaplan-Meier method. Differences between groups were assessed using the Log-rank (Mantel-cox) test. RESULTS 109 patients with a histopathologically confirmed diagnosis of breast cancer were included. The median age at treatment was 52 years (IQR:46-60). Of 103 patients with documented receptor status, 22 patients were ER+/HER2+, 32 ER+/HER2-, 20 ER-/HER2+ and 29 triple-negative. 68/105 patients had extra-cranial metastatic disease at treatment with SRT. A median of 2 lesions were treated per patient (range:1-15). Median OS for all patients was 67.4 weeks. Median OS was 91.4 weeks for ER+/HER2+ patients, 64.9 weeks for ER+/HER- patients, 71.4 weeks for ER-/HER2+ and 37 weeks for ER-/HER2- (p=0.001). Median OS was 55.1 weeks for patients with extra-cranial metastatic disease and 91.4 weeks in those without (p=0.017). Median OS was 72.1 weeks in patients with 1-2 brain metastases and 53.7 in those with extensive (3+) brain metastases, however this was not statistically significant (p=0.892). CONCLUSION A trend towards worse OS in patients with triple-negative receptor status and extra-cranial metastatic disease at treatment with SRT warrants further investigation.

P11.30.A Stereotactic Radiosurgery (SRS) for brain metastases in breast cancer: An evaluation of outcomes at a UK tertiary centre

Abstract Background Brain metastases (BM) occur in approximately 10-30% of patients with breast cancer (BC). Patients with advanced breast cancer are living longer, and the incidence of BM are increasing. Stereotactic Radiosurgery (SRS) has emerged as a strategy to treat BM. We evaluated the outcomes and potential prognostic factors of patients with BM treated with SRS. Material and Methods Retrospective review of patients treated with linac-based SRS for BM from BC in a single tertiary centre between August 2017-September 2021. Overall survival (OS), intracranial progression-free survival (IPFS), and prognostic factors were evaluated using Kaplan-Meier analysis, log-rank test, and Cox proportional-hazards model. Results 76 patients were included in the analysis. Out of these, 56 had first-line local treatment with SRS, either as primary (n=34) or adjuvant to surgery (n=22). Median age was 58 years old (range 37-86), and 88% had PS 0/1. One-year survival rate was 56%. Median OS and IPFS from SRS was 16 months (95% CI 8-24) and 7 months (95% CI 2-12), respectively. However, there were significant differences in OS (p&amp;lt;0.001) and IPFS (p=0.001) based on molecular subtypes. Patients with triple-negative breast cancer (TNBC) (n=14) had median OS of 7 months (95% CI 2-12), ER+/HER2- (n=22) median OS of 22 months, ER-/HER2+ (n=8) median OS of 4 months (95% CI 0-9), and ER+/HER2+ (n=11) median OS of 36 months. Similar trend was seen with IPFS. Patients with progressive extracranial disease compared to stable disease had shorter median OS (4 months vs 23 months, HR 2.4, p=0.01) and median IPFS (4 months vs 13 months, HR 2, p=0.03). Age ≥65 years was associated with shorter median OS (4 vs 23 months, HR 2.3, p=0.02). Patients with ≥4 brain metastases had shorter IPFS (4 months vs 11 months, HR 2.4, p=0.012), but no significant difference in OS. Volume of metastases did not affect outcome in this series. 30% of patients progressed intracranially after first-line SRS. 94 % had out-of-field recurrences, and 6% in-field recurrences. 59% had further SRS, 12 % WBRT, 6% surgery, and 23% had no further local treatment. 26 patients had second-line local treatment with SRS after first-line SRS (n=9), WBRT (n=9), or surgery +/- WBRT (n=8). There were no significant differences in outcome based on the modality of first-line local treatment. Conclusion SRS is an effective treatment for BM from BC. There were significant differences in survival based on age, molecular subtypes, and extracranial disease status.

Staged radiosurgery alone versus postoperative cavity radiosurgery for patients with midsize-to-large brain metastases: a propensity score matching analysis.

The authors investigated and compared the results of staged stereotactic radiosurgery (S-SRS) alone and those of postoperative cavity SRS (C-SRS) for patients with midsize-to-large brain metastases (BMs). Patients with BMs who had undergone S-SRS or C-SRS during the period from 2010 to 2020 were retrospectively identified from an institutional database. The two treatment groups were generated by propensity score matching (PSM; match ratio 2:1) based on 13 potential prognostic covariates: sex, age, Karnofsky Performance Status, type of primary cancer, timing of BM diagnosis, extracranial disease status, driver mutations, molecular target therapy, neurological symptoms, number of BMs, location of BMs treated with S-SRS or C-SRS, maximal tumor or cavity volume, and cumulative intracranial tumor volume. Patient survival and control of intracranial disease were compared between the S-SRS and C-SRS groups using time-dependent analyses taking into account competing events. In total, 110 patients in the S-SRS group and 62 in the C-SRS group were selected by PSM. In the S-SRS group, the median interval between the two radiosurgical sessions was 21 days, and the median total prescription dose was 28 Gy at 50%. In the C-SRS group, the median time from surgery to C-SRS was 16 days, and the median prescription dose delivered to the surgical cavity was 15 Gy at 55%. At the time point of data set fixation, 129 patients had died, 43 were alive, and none had been lost to follow-up. The 2-year survival rates for the S-SRS and C-SRS groups after the initial intervention were 33% and 37% and the median survival times were 14.8 and 17.5 months, respectively (p = 0.33). The 2-year cumulative neurological mortality rates were 11% and 9%, respectively (p = 0.65). The 2-year local failure rates were 32% and 12% (p = 0.036) and the 2-year distant recurrence rates were 55% and 58%, respectively (p = 0.53). The 2-year leptomeningeal disease development rates were 9% and 25%, respectively (p = 0.007). The present study revealed no significant difference in overall survival or cumulative neurological mortality between the S-SRS and C-SRS groups. The local control failure rate was significantly higher in the S-SRS group, whereas the incidence of leptomeningeal disease development was significantly higher in the C-SRS group.

Brain metastasis as first and only metastatic relapse site portends poor outcomes in patients with advanced HER2+ breast cancer.

1045 Background: In patients (pts) with stable or no extracranial disease (ECD) presenting with breast cancer brain metastases (BCBrMs), current guidelines recommend pts receive local therapy with radiation +/- surgery, without changing systemic therapy. However, preliminary studies suggest that pts with isolated HER2+ BCBrM without ECD have inferior overall survival (OS) compared to pts with concurrent ECD. Our study further explores the implications of ECD status on intracranial progression free survival (iPFS) and OS. Methods: Retrospective analysis was performed on data from 153 pts diagnosed with initial HER2+ BCBrM who received CNS radiation at Duke between 2008 and 2020. Demographics, dates of metastatic and BCBrM diagnosis, ECD status at first CNS event, systemic therapy, and outcomes were collected. The primary endpoint was iPFS defined as the time from first CNS radiation to the subsequent documentation of intracranial progression (RANO-BM). OS was defined as time from first CNS radiation and first metastatic disease to date of death or last known contact. ECD status was defined by RECIST1.1 from systemic staging scans within 30 days of first CNS event. Results: In this cohort of 153 pts with HER2+ BCBrMs undergoing CNS radiation, &gt; 70% of pts with known ECD status had controlled systemic disease: either no ECD (27%) or stable/responding disease (44%). 64% of pts’ tumors were ER+. Median age was 50 years (range 24 – 75). Most pts (59%) developed first CNS event during adjuvant or 1st/2nd line metastatic therapy. CNS radiation treatment included 48% of pts receiving SRS only, 9% WBRT only, and 43% SRS and WBRT. All pts with no ECD presented with isolated BCBrMs as first metastatic disease. Among pts with known ECD status, OS from initial metastatic disease to death was markedly worse for pts with isolated brain metastases or no ECD (median = 28.4m, 95% CI: 18.1 to not reached) compared to those with progressive or stable/responding ECD (48.8m, 95% CI: 40.5 to 65.0; and 68.1m, 95% CI: 55.2 to 85.7, respectively; log-rank p = 0.004). OS from first CNS involvement to death was significantly worse for pts with progressive ECD (17.8m, 95% CI: 13.7 to 28.8) versus stable/responding (36.6m, 95% CI: 29.7 to 45.2) or no ECD (28.4m, 95% CI: 18.1 to not reached; log-rank p = 0.008). iPFS did not differ statistically among subgroups of pts with known ECD status: progressive ECD (median = 7.7m), no ECD (8.3m), or stable/responding ECD (11.2m) (log-rank p = 0.15). Conclusions: Overall survival in pts with HER2+ isolated BCBrM was markedly inferior to that of pts with progressive or stable/responding ECD. Studies investigating initiation of brain penetrable HER2-targeted therapies earlier in the disease course of isolated HER2+ BCBrMs pts are warranted.

Общая выживаемость и факторы прогноза у пациентов с метастазами рака почки в головной мозг после нейрохирургического лечения

Treatment of patients with brain metastases is an urgent problem that must be chosen as part of an integrated approach to detection, based on the characteristics of detection, the patient’s condition, and the severity of neurological deficit. The introduction of new techniques used with the use of neurosurgical and drug treatment, the original method of radiation therapy can increase the survival of patients, as well as improve the quality of life. This article presents the results of a retrospective analysis of the overall survival of patients with cerebral metastases of kidney cancer after neurosurgical resection. The aim of the study is to study the overall survival rates in patients with kidney cancer metastases in the brain after neurosurgical treatment. Material and methods. A retrospective analysis of the results of treatment of 114 patients with brain metastases from kidney cancer who received neurosurgical treatment at the National Medical Research Center of Oncology named after N.N. Blokhin. In the overall survival analysis, survival data were found in 102 (89.5%) of 114 patients. Of these, 80 (78.4%) patients died, and 22 (21.5%) patients are still being followed up. The extracranial disease status (ECM) at the time of surgical treatment was known in 82 (71.9%) patients, of which 45 (54.8%) patients underwent ECM, and 37 (45.1%) did not. In 92 (90.1%) patients, total removal of brain metastases (BM) with perifocal and perivascular zones was performed, in the rest of the patients; fragmentary resection of the focus was performed. Results. Overall survival (OS) after neurosurgical treatment 54.4%; 35.6%; 30.8% and 19% at 12, 24, 36, and 60 months, respectively, with a median OS of 13.8 months (95% CI, 10.29 to 18.6). Statistically significant predictors of overall survival were established: Karnofsky index ≥80% (p&lt;0.0001) and absence of extracranial metastases (p=0.0107). The best survival rates were achieved in the group of patients with a history of nephrectomy and targeted or immunotherapy after neurosurgical treatment. Conclusion. Neurosurgical treatment, which is used with microsurgery and intraoperative navigation, allows a rapid reduction in neurological symptoms, good local control in the area of the remote focus with the course of postoperative complications. Neurosurgical intervention includes consideration of overall survival rates and, as part of anticancer drug therapy that increase overall survival rates.

373P Brain metastases: Extracranial disease status as a prognostic factor after whole brain radiotherapy. Results from a prospective, population-based study

Deciding the optimal treatment for patients with brain metastases (BM) remains challenging. For patients not candidates for surgery (S) or stereotactic radiosurgery (SRS), prognostic factors to identify those with a survival benefit after whole brain radiotherapy (WBRT) are needed. Prognostic scoring systems based on clinical trial data exist, but extracranial disease status is not part of most of these systems. Clinical trials typically include selected patients (i.e ≤4 BM, good performance status [PS]).

OTHR-10. Diverse survival outcomes of HER2+ Breast Cancer Brain Metastases (BrCBM) presenting with isolated brain relapse compared to those with concurrent extracranial disease

BackgroundIn patients with isolated HER2+ BrCBM and no extracranial disease (ECD), there are no consensus guidelines on optimal treatment approaches following CNS-directed therapy. Our goal was to determine the implications of ECD at time of first HER2+ BrCBM on intracranial progression-free survival (PFS1) and overall survival (OS).MethodsRetrospective analysis was performed on 77 patients with HER2+ BrCBM who received 1st CNS radiation from 2006–2020. Demographics, dates of metastatic and intracranial diagnosis, ECD status at 1st BrCBM, and outcomes were collected. The primary endpoint was PFS1 defined as time from first CNS radiation to the subsequent documentation of intracranial progression (RANO-BM). OS was defined as time from 1st CNS radiation and 1st metastatic disease to date of death/last known alive. ECD status was defined by RECIST1.1 from staging scans within 30 days of 1st BrCBM.ResultsIn this patient cohort, 25% (19/77) had isolated brain relapse/no ECD. Median age was 50 years. Most patients (58%) developed first BrCBM during adjuvant or early-line metastatic therapy. All patients with no ECD presented with isolated brain relapse as first metastatic presentation. Patients with concurrent ECD presented with first BrCBM at a median of 16.6m (95% CI: 10.5 to 25.3) after initial metastatic presentation. Median OS from initial metastatic presentation to death was worse for patients with isolated brain relapse (25.3m, 95% CI: 16.8 to 35.3) compared to those with concurrent ECD (49.7m, 95% CI: 43.2 to 62; p=0.01). Median OS from first CNS involvement to death was not statistically different amongst groups.ConclusionsPatients with isolated HER2+ BrCBM as their initial metastatic event have substantially worse OS compared to patients with concurrent ECD developing CNS metastases later in their disease course. This population with isolated brain relapse deserves investigation of novel treatment algorithms, including earlier introduction of brain-penetrable HER2-targeted agents.