Surgical Resection Of Brain Metastases Research Articles

SINGLE INSTITUTION RETROSPECTIVE ANALYSIS OF COMPLICATIONS ASSOCIATED WITH SURGICAL DEBULKING OF BRAIN METASTASIS

Abstract AIMS Surgical resection of brain metastasis is associated with complications, which worsen patient’s quality of life, results in oncological treatment delays and death. Surgical complication data aids decision making, leads to objective risk benefit analysis and informed consent. The aim of this study is to quantify rates, types and risk factors for complications related to surgical debulking of brain metastasis. METHOD Retrospective analysis on adult patients with brain metastasis, who underwent surgical debulking between 2017 and 2023 at Royal Preston Hospital. Data collected included demographics, diagnosis, 30-days post-operative complications, 30-days mortality, 30-days post-operative palliation, primary tumour, Karnofsky-Performance Score (KPS), first vs. repeat resection, use of drain and type of suture materials etc. Univariate analysis was carried out using Graphpad software. RESULTS Two-hundred and twenty-seven patients qualified. The most common primaries were lung (n=93, 41%), breast (n=43, 18.9%), and skin (n=31, 13.7%). The most common complications were Hospital-acquired pneumonia (HAP) (n=27, 11.9%), surgical site infection (SSI) (n=19, 8.4%), wound dehiscence (n=14, 6.2%), thromboembolic events (n=12, 5.3%) and CSF leak (n=8, 3.5%). Thirty days mortality and post-operative palliation (due to surgical complications) were both 3.5% each (n=8). Two-hundred and six (93.2%) had KPS ³70 whilst 15 (6.8%) had KPS < 70 [range 30-60 pre-operatively (median 60)). KPS < 70 was statistically significant for post-operative palliation (p=0.01), HAP (0=0.02) and urine infection (p=0.002), but not for 30-day mortality. Twenty-five (11.1%) patients undergoing repeat resections, experienced higher wound infections (p=0.002). CONCLUSION Surgical debulking is associated with significant post-operative complications, with 7% either dying or not receiving any further treatment, 18.1% percent developing serious wound complications (SSI, CSF leak, Wound dehiscence) and 19.4% experiencing significant medical complications (HAP/UTI/Thromboembolism). Pre- operative KPS < 70 and repeat resections are associated with statistically increased risk of complications.

Survival Impact of Postoperative Whole-brain Radiotherapy and Systemic Chemotherapy After Surgical Resection of Brain Metastases.

Resection of brain metastases is a well-established treatment modality that can prolong the survival of patients for whom surgery is indicated. Whole-brain radiotherapy (WBRT) has been the standard postoperative therapy. In recent years, however, clinicians have increasingly avoided WBRT due to its associated adverse events. This study investigated the impact of postoperative WBRT and systemic chemotherapy as prognostic factors on the survival of patients who had undergone resection of brain metastases. The study subjects were 172 patients who underwent surgical resection for brain metastases. Comparative analyses of survival after WBRT and systemic chemotherapy were performed. Postoperative WBRT had no survival-prolonging effect, whereas postoperative systemic chemotherapy prolonged survival. A comparison based on the number of systemic chemotherapy regimens administered prior to surgery showed that fewer regimens correlated with a better prognosis. The addition of WBRT after surgical resection of brain metastases is no longer a standard treatment strategy and systemic chemotherapy after surgery is a positive prognostic factor.

Distribution characteristics and prognosis of tumor-infiltrating lymphocytes in the brain metastases of small cell lung cancer: a retrospective cohort study.

The efficacy of immunotherapy for brain metastases from small cell lung cancer (SCLC) is relatively low, and the tumor microenvironment of SCLC brain metastases is still unknown. Therefore, we investigated the distribution of tumor-infiltrating lymphocytes (TILs) and the expression of programmed cell death-ligand 1 (PD-L1) in patients with brain metastases from SCLC to explore the tumor microenvironment of SCLC brain metastases. A retrospective analysis was performed on 12 surgical specimens of brain metastases from patients with SCLC treated in the Department of Neurosurgery of The First Affiliated Hospital of Anhui Medical University from June 2017 to June 2022. The inclusion criteria for this study were the following: (I) a pathologically confirmed diagnosis of SCLC brain metastases; (II) surgical resection of brain metastases; (III) age >18 years; (IV) and complete clinical data. Patient-related data were retrieved from the inpatient medical record system, telephone follow-up of patients date of death, and overall survival (OS). The immunofluorescence-based tissue microenvironment analysis panel (MAP) was utilized for the detection of TILs, including CD3, CD8, programmed cell death 1 (PD-1), and PD-L1, in formalin-fixed and paraffin-embedded archival specimens of brain metastases. The expression levels of PD-L1 in tumor cells were detected by immunohistochemistry. The correlation between the OS and the above-mentioned markers was analyzed in the 12 patients. Twelve patients were included in the study. The patients' ages ranged from 51-78 years with a median of 68 years, with 1 female and 11 males. Among 12 patients with SCLC brain metastases: positive rates of CD3+ TILs in the tumor parenchyma vs. tumor stroma were 0.60%±0.94% vs. 1.76%±2.72% (P=0.01), respectively; positive rates of CD8+ TILs in the tumor parenchyma vs. tumor stroma were 0.80%±0.78% vs. 2.46%±3.72% (P=0.02), respectively. There was no co-expression of CD8+ and PD-1+ TILs in the tumor parenchyma of 11 cases, and the infiltration density of coexpressed CD3+ and PD-1+ TILs was more than 10/mm2 in only 1 case. There was no coexpression of CD3+ and PD-1+ TIL in the stroma of 10 cases, and the infiltration density of CD8+ and PD-1+ TILs was more than 10/mm2 in 2 cases. Immunohistochemistry was used to detect the expression of PD-L1 in 12 cases of SCLC metastatic lesions, and 3 cases (25%) were positive. Survival analysis showed that patients with positive intraepithelial CD3+ TILs had significantly longer OS [hazard ratio 3.383, 95% confidence interval (CI): 0.959-11.940; P=0.04]. Our study further demonstrated the immune microenvironment of SCLC brain metastases. The distribution of TILs in SCLC brain metastases is low and mainly distributed in the stroma, with the expression of PD-L1 in these tumor tissues being low. Further exploration of the immune microenvironment of SCLC brain metastases is of great significance for potential treatment.

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

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

Effect of sarcopenia and frailty on outcomes among patients with brain metastases.

Sarcopenia and frailty have been associated with increased mortality and duration of hospitalization in cancer. However, data investigating these effects in patients with brain metastases remain limited. This study aimed to investigate the effects of sarcopenia and frailty on clinical outcomes in patients with surgically treated brain metastases. Patients who underwent surgical resection of brain metastases from 2011 to 2019 were included. Psoas cross-sectional area and temporalis thickness were measured by two independent radiologists (Cronbach's alpha > 0.98). Frailty was assessed using the Clinical Frailty Scale (CFS) pre-operatively and post-operatively. Overall mortality, recurrence, and duration of hospitalization were collected. Cox regression was performed for mortality and recurrence, and multiple linear regression for duration of hospitalization. 145 patients were included, with median age 60.0 years and 52.4% female. Psoas cross-sectional area was an independent risk factor for overall mortality (HR = 2.68, 95% CI 1.64-4.38, p < 0.001) and recurrence (HR = 2.31, 95% CI 1.14-4.65, p = 0.020), while post-operative CFS was an independent risk factor for overall mortality (HR = 1.88, 95% CI 1.14-3.09, p = 0.013). Post-operative CFS (β = 15.69, 95% CI 7.67-23.72, p < 0.001) and increase in CFS (β = 11.71, 95% CI 3.91-19.51, p = 0.004) were independently associated with increased duration of hospitalization. In patients with surgically treated brain metastases, psoas cross-sectional area was an independent risk factor for mortality and recurrence, while post-operative CFS was an independent risk factor for mortality. Post-operative frailty and increase in CFS significantly increased duration of hospitalization. Measurement of psoas cross-sectional area and CFS may aid in risk stratification of surgical candidates for brain metastases.

Image Guided Intraoperative Radiation Therapy After Surgical Resection of Brain Metastases: A First In-Human Feasibility Report

PurposeA correct placement of the applicator during intraoperative radiotherapy (IORT) for brain metastasis is of paramount importance, in order to deliver a precise and safe treatment. The applicator-to-surface contact assessment cannot be performed under direct observation, as the applicator itself limits the visual range. No image-guided (IG) verification is currently performed intracranially. We hypothesize that IG-IORT would assure a more precise delivery in the target area. We describe our workflow in a first in-human experience. Methods and MaterialsPhantom-based measurements were performed to reach the best cone-beam computed-tomography (CBCT) imaging quality possible. Once defined, a clinical feasibility study was initiated. An in-room CBCT device is used to acquire intraoperative images after placing the applicator. Repositioning the applicator is thereafter discussed with the surgeon, according to the imaging outcomes, if required. ResultsAn optimal image quality was achieved with 120-kV voltage, 20-mA current and a tube current–time product of 150 mAs. An additional 0.51–mSv patient exposure was calculated for the entire procedure. The wide dynamic range (−600 HU to +600 HU) of CBCT and a 27-HU mean CT values difference between brain tissue and spherical applicator allows distinguishing both structures. In this first in-human experience, the applicator was repositioned after evidencing air gaps, assuring full applicator-to-surface contact. ConclusionThis first in-human procedure confirmed the feasibility of kilovoltage IG-IORT in a neurosurgical setting. A prospective study has been initiated and will provide further dosimetric details.

Multicentric Assessment of Safety and Efficacy of Combinatorial Adjuvant Brain Metastasis Treatment by Intraoperative Radiation Therapy and Immunotherapy

PurposeFollowing surgical resection of brain metastases (BMs), intraoperative radiation therapy (IORT) provides a promising alternative to adjuvant external beam radiation therapy (EBRT) by enabling superior organ at risk preservation, reduction of in-hospital times and timely admission to subsequent systemic treatments, which increasingly comprise novel targeted immunotherapeutic approaches. We sought to assess safety and efficacy of IORT in combination with immune checkpoint inhibitors (ICIs) and other targeted therapies (TTs). MethodsIn a multicentric approach incorporating individual patient data from six international IORT centers, all patients with BMs undergoing IORT were retrospectively assessed for combinatorial treatment with ICIs/TTs and evaluated for toxicity and cumulative rates, including wound dehiscence, radiation necrosis (RN), leptomeningeal spread (LMS), local control (LC), distant brain progression (DBP) and estimated overall survival (OS). ResultsA total of 103 lesions with a median diameter of 34 mm receiving IORT combined with immunomodulatory systemic treatment or other TTs were included. The median follow up was 13.2 (1.2-102.4) months and the median IORT dose was 25 (18-30) Gy prescribed to the applicator surface. There was one grade 3 adverse event related to IORT recorded (2.2%). A 4.9% cumulative RN rate was observed. The 1-year LCR was 98.0% and the 1-year DBP-free rate 60.0%. Median time to DBP was 5.5 (1.0-18.5) months in the subgroup of patients experiencing DBP and the cumulative LMS rate was 4.9%. The median estimated OS was 26 (1.2-not reached) months with a 1-year survival rate of 74.0%. Early initiation of IT/TT was associated with a non-significant trend towards improved DBP rate and OS. ConclusionThe combination of ICIs/TT with IORT for resected BMs does not seem to increase toxicity, while yielding encouraging local control outcomes in the difficult-to-treat subgroup of larger BMs. Time gaps between surgery and systemic treatment could be shortened or avoided. The definitive role of IORT in local control after BM resection will be defined in a prospective trial.

Outcomes Following Early Postoperative Adjuvant Radiosurgery for Brain Metastases

Adjuvant 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. To evaluate whether adjuvant SRS delivered within a median of 14 days after surgery is associated with improved LF without a concomitant increase in PTRE. This 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. Timing of adjuvant SRS (14, 21, and 30 days postoperatively). LF and PTRE, according to modified Response Assessment in Neuro-Oncology Brain Metastases criteria. There 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). In 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.

Correlation of Brain Metastasis Genomic Alterations with Preoperative Imaging Features

The aim of this study was to examine associations between genomic alterations in brain metastases and common preoperative imaging findings including overt intratumoral hemorrhage, cystic features, and edema. A single-center, retrospective study was performed including patients who underwent surgical resection of brain metastasis with available preoperative magnetic resonance imaging (MRI). Next-generation sequencing of more than 500 coding genes was performed on the resected brain metastases. Preoperative MRI was reviewed to identify the presence of intratumoral hemorrhage, cystic features, and edema in the resected brain metastasis. Genomic data were then correlated with the imaging features using univariate and multivariate nominal logistic regression analyses. We included 144 brain metastases from 141 patients in the study cohort. Half (72) of the metastases had an intratumoral hemorrhage, 26 (18%) had cystic features, and 130 (90%) had edema. Mutations in TP53 were associated with a reduced risk of intratumoral hemorrhage (odds ratio [OR] 0.2, 95% confidence interval [CI] 0.07-0.5, P< 0.001). Mutations in RB1 and CCND1 were associated with elevated risk of the metastasis having cystic features (OR 10.3, 95% CI 2.0-52.6, P= 0.005, OR 18.4, 95% CI 2.2-155.3, P= 0.008, respectively). PIK3CA mutations were associated with a reduced risk of peritumoral edema (OR 0.2, 95% CI 0.04-0.8, P= 0.03). Several genomic alterations in brain metastases are associated with MRI features including hemorrhage, cystic features, and edema. These results provide insight into tumor biology and patients at risk of developing these imaging features.

Socio-economic disparities influence likelihood of post-operative radiation to resection cavities of metastatic brain tumors.

Irradiating the surgical bed of resected brain metastases improves local and distant disease control. Over time, stereotactic radiosurgery (SRS) has replaced whole brain radiotherapy (WBRT) as the treatment standard of care because it minimizes long-term damage to neuro-cognition. Despite this data and growing adoption, socio-economic disparities in clinical access can result in sub-standard care for some patient populations. We aimed to analyze the clinical and socio-economic characteristics of patients who did not receive radiation after surgical resection of brain metastasis. Our sample was obtained from Clinformatics® Data Mart Database and included all patients from 2004 to 2021 who did or did not receive radiation treatment within sixty days after resection of tumors metastatic to the brain. Regression analysis was done to identify factors responsible for loss to adjuvant radiation treatment. Of 8362 patients identified who had undergone craniotomy for resection of metastatic brain tumors, 3430 (41%) patients did not receive any radiation treatment. Compared to patients who did receive some form of radiation treatment (SRS or WBRT), patients who did not get any form of radiation were more likely to be older (p = 0.0189) and non-white (p = 0.008). Patients with Elixhauser Comorbidity Index ≥3 were less likely to receive radiation treatment (p < 0.01). Fewer patients with household income ≥ $75,000 did not receive radiation treatment (p < 0.01). Age, race, household income, and comorbidity status were associated with differential likelihood to receive post-operative radiation treatment.

Prioritizing Radiation and Targeted Systemic Therapy in Patients with Resected Brain Metastases from Lung Cancer Primaries with Targetable Mutations: A Report from a Multi-Site Single Institution

Brain metastases (BrM) are a common complication of non-small cell lung cancer (NSCLC), present in up to 50% of patients. While treatment of BrM requires a multidisciplinary approach with surgery, radiotherapy (RT), and systemic therapy, advances in sequencing have improved outcomes with targetable alterations in PDL-1, EGFR, ALK, and KRAS mutations. With a push towards molecular characterization of cancers, we sought out to examine outcomes by treatment modalities at our institution with respect to prioritizing RT and targeted therapies. After IRB approval, we identified patients treated with a surgical resection of BrM from NSCL primaries between 2011 to 2022 at 5 sites at our institution. Tumor molecular profiles were reviewed and patients with PDL-1, EGFR, ALK, and KRAS mutations were evaluated by a treatment modality: surgery alone or in combination with RT (SRS, WBRT) and/or systemic therapy (TKIs -1st-3rd generations, immunotherapy). The primary endpoints were in-brain freedom from progression (FFP) and overall survival (OS). SAS Studio version 4.4 was used to perform statistical analyses. We identified 272 patients with 162/272 (60%) patients with adequate follow-up included in this analysis. The median follow-up was 27.8 months (range, 0.43 - 134.45 months). There were 59.2% females and 40.7% males, with median ages at diagnosis of 67 years for females and 66 for males, respectively. Of the entire cohort, 102/162 (63%) patients received adjuvant combination RT and systemic therapy, and 60/162 (37%) received adjuvant monotherapy (p <0.0001). The use of systemic therapy was associated with 9.89 months median time to progression vs 4.87 months without it (p = 0.077), respectively. Similarly, patients treated with a combination of RT and systemic therapy had a median FFP time of 9.77 months vs 5.28 months (p = 0.064). No significant difference in OS was found with or without systemic therapy. After resection of BrM from NSCLC with PDL-1, EGFR, ALK, and KRAS mutations, we found that systemic therapy, including TKIs and immunotherapy, may have an increasing role in delaying time to progression. At our institution, as we continue to identify actionable mutations, a statistically significant number of patients continue to be treated with a combination of RT and systemic therapies with a trend toward superior FFP.

A Phase II Trial of Intraoperative Radiotherapy after Surgical Resection of Brain Metastases: Feasibility and Efficacy NCT04847284

Intraoperative radiation therapy (IORT) is an alternative to local radiation therapy for brain metastases, reducing total treatment time, and improving patient comfort, but the most effective dose is unknown. The objective of this study is to evaluate the efficacy and safety of IORT in patients with surgical excision of brain metastases at a dose of 20 Gy. This trial is a single-institution, open-label, prospective, non-randomized study for intraoperative radiotherapy immediately after resection of brain metastases. Registered in January 2021, currently ongoing, planned to enroll 25 patients with IK ≥70, brain damage newly diagnosed by MRI, without dural contact and at least 1 cm to the optic nerve, chiasm and brainstem. In the baseline visit, the General Cognitive State will be carried out: Minimum Mental State Exams. Specific cognitive study: 1- Processing speed (SYmbol digit modalities test), 2- Executive function (TMT, back and forward digit span test, phonological and semantic verbal fluency test, Stroop color-word test), 3- Verbal memory (FCSRT). Quality of life will be monitored by completing the EORTC QL-C30 and BN20 questionnaires. Intraoperative radiation therapy will be performed with a 50 kV low energy X-ray portable linear accelerator using spherical applicators ranging from 1.5 to 4 cm kV to deliver 20 Gy to the surface. During IORT a maximum dose (DMax) of 8 Gy will be allowed to the optic nerve/chiasm and brainstem structures. MRI will be performed 72 hours after IORT. Neurocognitive Test and MRI after 6 weeks and every 3 months. The primary endpoint will be local progression free survival (PFS). Secondary endpoints will be overall survival, time to save cancer therapy, cognitive performance and quality of life, as well as IORT-related neurotoxicity complications will be evaluated according to the scale of the CTACAE version 4. The analysis of the median local progression free survival, overall survival will be analyzed using the Kaplan-Meier curve (long range test). All results will be considered statistically significant with a p value < 0.05. The statistical analysis will be carried out with statistical software. The trial is open and ongoing to recruitment; we have included 7 patients. The 85.7% were male, mean age was 61.4 years range (43-74). The 57.1% were lung cancer metastases. For now, no tumor recurrence or neurocognitive complications have been observed and then once you have the results ready, we will publish them. The limited current literature on the use of IORT in brain metastases appears to show efficacy and safety, but the most effective dose is unknown as well as whether it is as effective as other radiotherapy alternatives. Our study is ongoing and needs to be completed and evaluated with more follow-up in order to reach definitive conclusions.

P20.01.A CLINICAL APPLICATION OF RELATIONSHIP BETWEEN GENETIC ALTERATION AND INTRAOPERATIVE FLUORESCENCE ACTIVITY OF 5-AMINOLEVULINIC ACID IN BRAIN METASTASIS OF NON-SMALL CELL LUNG CANCER

Abstract BACKGROUND Distant metastasis into major organ is a major cause of death in cancer patients. Especially, metastasis to brain is known to duplicate the mortality of cancer patients because brain metastasis makes patients neurologically independent in daily activities. Despite surgical resection of brain metastasis is a core strategy for management, it is not possible for all brain metastasis due to eloquent location, multiple lesions, or clinical condition of patient. With advancement of technology in brain tumor surgery, fluorescence image, such as 5-aminolevulinic acid (5-ALA), can help detect the residual tumor during surgery. Recently, genetic alteration of cancer is additionally considered as prognostic factor with being added into traditional prognostic system, such as GPA scoring system. The primary objective of this study is to examine the fluorescence patterns of 5-ALA in brain metastasis surgery and investigate the results of genetic alteration in brain metastasis using next generation sequencing technique. MATERIAL AND METHODS Medical records of patients with brain metastasis of non-small cell lung cancer at our center from January 2017 to June 2022. Among them, the patients who were treated with surgical resection under 5-ALA fluorescence image and had NGS results were included in the analysis. RESULTS Total 72 patients were eligible for analysis. Mean follow-up duration was 12.36 months. Recurrence occurred in 28 (38.9%) patients and 46 (63.9%) patients succumbed to NSCLC. Mean recurrence-free survival (RFS) was 14.57 months and mean overall survival (OS) was 16.29 months. Strong fluorescence was obtained in 56 (77.8%) patients during surgery. In the NGS data of brain metastasis, genetic alteration of cell cycle regulation, DNA repair, tumorigenesis, proliferation, epigenetic regulation, and cancer immunology were detected in 73.6%, 44.4%, 56.9%, 66.7%, 30.6%, and 2.8%, respectively. In multivariate analysis, KPS, RPA class, extent of resection, modality of adjuvant treatment, genetic alteration of cell cycle regulation and cellular proliferation were associated with RFS. Additionally, age, KPS, status of NSCLC, RPA class, GPA score, modality of adjuvant treatment, genetic alteration of cell cycle regulation and cellular proliferation were associated with OS. CONCLUSION The presenting study suggested that microscopic complete resection with assist of fluorescence image could improve clinical outcome, and strong fluorescence image could reflect the genetic alteration of cell cycle regulation and cellular proliferation which are poor prognostic factors.

P11.31.B LEPTOMENINGEAL SPREAD AFTER POSTOPERATIVE STEREOTACTIC RADIOTHERAPY FOR BRAIN METASTASES

Abstract BACKGROUND Stereotactic radiotherapy (SRT) is the preferred treatment after surgical resection of brain metastases to improve local tumour control compared to observation. Some recent studies suggest that leptomeningeal metastases (LMM) occur more often after postoperative SRT compared to primary SRT with brain metastases in situ. This may be caused by tumour cells spillage during surgery. The aim of this study was to determine the incidence of LMM after postoperative SRT of brain metastases in our institution. MATERIAL AND METHODS All patients treated with postoperative SRT for brain metastases in our hospital between 2015 and 2020 were included in this retrospective analysis. LMM was diagnosed by a neuro-radiologist (RH) on a cerebral MRI. LMM, overall survival, and time to local recurrence (LR) were estimated from date of SRT, using the Kaplan-Meier method. RESULTS In total, 53 patients with 84 brain metastases were included in the analysis. Median age at SRT was 58 years (range 45 - 75 years). Median survival in this cohort was 16 months (IQR 9 - 26 months). Eight of 53 patients (15%) developed LMM at a median of 9 months after SRT. Using Kaplan-Meyer analysis, the incidence of LMM at 1 and 2 years was 15% and 19%, respectively. Twelve patients (23%) of 53 experienced LR at a median of 9 months. The 1 and 2-year actuarial incidence was 14% and 35%, respectively. CONCLUSION In our cohort, the incidence of LMM after postoperative SRT for brain metastases is comparable to other studies. Studies are needed to determine whether the incidence of LMM after postoperative SRT can be reduced.

Effect of blood type on mortality among patients with brain metastases

ObjectiveABO blood type has been associated with mortality among patients with cancer, but this association has thus far not been investigated among patients with brain metastases. Hence, we aimed to investigate the association between ABO blood type and mortality among patients who underwent surgical resection of brain metastases. MethodsA single-center retrospective study of patients who underwent surgical resection of brain metastases between 2011 and 2019 was conducted. Cox proportional hazards models were constructed, adjusting for potential confounders, to evaluate whether blood type was independently associated with overall mortality. ResultsA total of 158 patients were included in the analysis. The mean (SD) age of the cohort was 59.3 (12.0) years, and 67.7% of patients were female. The median overall survival of patients with blood type AB was 11.2 months, while the median overall survival of patients with blood types O, B, and A were 11.7, 13.5, and 14.4 months respectively. On univariate analysis, patients with blood type AB had a higher risk of overall mortality (p = 0.017). On multivariate analysis adjusting for potential confounders, blood type AB was again associated with a higher risk of overall mortality (HR: 2.29, 95% CI: 1.11–4.72, p = 0.025). ConclusionBlood type AB was independently associated with a higher risk of overall mortality among patients who underwent surgical resection of brain metastases, indicating the potential prognostic value of ABO blood type in brain metastases.

CHD5 gene variant predicts leptomeningeal metastasis after surgical resection of brain metastases of breast cancer.

Leptomeningeal metastasis (LM) is a complication of surgery for brain metastasis and is a risk factor of poor prognosis. The risk of LM is particularly high after surgery for a breast cancer metastasis to the brain. If the risk of LM after surgical resection for a brain metastasis were predictable, appropriate adjuvant therapy could be administered to individual patients to improve their prognosis. The present study aimed to reveal the genetic characteristics of brain metastases as means of predicting LM in breast cancer patients. Ten patients with brain metastases of breast cancer presented LM after surgical resection were analyzed by whole-exome sequencing. A chromodomain-helicase-DNA-binding protein 5 (CHD5) gene alteration was detected in nine cases (90%), including a nonsynonymous variant in four cases and copy number deletion in five cases. CHD5 protein expression was lost in nine cases and had decreased in one case. The frequency of CHD5 gene alteration in brain metastases with LM was significantly higher than in primary breast cancer (2.3%) or in brain metastases of breast cancer (0%) (p < 0.0001). These results suggested that the CHD5 gene alteration was associated with LM after surgical resection of breast cancer brain metastases. Searching for the gene alteration might predict the LM risk after surgical resection.

Postoperative Management of Recurrence After Radiosurgery and Surgical Resection for Brain Metastases and Predicting Benefit From Adjuvant Radiation

Stereotactic radiosurgery (SRS) is often used as upfront treatment for brain metastases. Progression or radionecrosis after SRS is common and can prompt resection. However, postoperative management strategies after resection for SRS failure vary widely, and no standard practice has been established. In this approved study, we retrospectively reviewed patients who received SRS for a brain metastasis followed by resection of the same lesion. We extracted patient-, disease-, and treatment-related variables and information on disease-related outcomes. Univariate and multivariate analyses of clinicopathologic variables were used to create a model to predict factors associated with local failure (LF). A total of 225 patients with brain metastases treated with SRS from 2009 to 2017 followed by surgical resection were identified. Overall, 65% of cases had gross total resection (GTR) on postoperative imaging review. Twenty-one patients (9.3%) received adjuvant radiation therapy to the surgical cavity, and 204 (90.7%) were observed. Of these 204 patients, 118 had GTR with evidence of tumor within the pathology specimen. With a median follow-up of 13 months after resection, 47 patients (40%) developed LF after surgery. After salvage resection of a brain metastasis initially treated with SRS, the observed LF rate was 40% among those who had a GTR and evidence of tumor on pathologic examination. This LF rate is sufficiently high that adjuvant radiation to the surgical bed after salvage resection should be considered in these cases when there is tumor in the pathology, even after a GTR.

Effectiveness of combined therapy for patients with brain metastasis

Introduction. Incidence of brain metastases rises in recent years. Local control after surgical resection of brain metastases is a priority for patients with limited intracranial disease and controlled primary tumor. Surgery should be combined with other methods because of the high risk of local recurrences.Aim. To analyze the overall survival (OS) and influencing factors for patients with brain metastasis after combined therapy. Materials and methods. The retrospective study included 196 patients with stable systemic cancer or available systemic therapy in cases of progressive disease. All patients had from 1 to 3 brain metastasis. Overall survival and influencing factors after surgical and combined therapy were analysed.Results. Median OS for the entire cohort was 16.9 months. The highest levels of OS were achieved for patients with renal cancer (median OS 32.5 months). For patients with non-small cell lung cancer, breast cancer, melanoma and other cancers OS were 18.8; 19.9; 11.0 and 15.3 months, appropriately. Age, continuation of local therapy in brain (surgical intervention, stereotactic radiosurgery), using of the cisplatin for patients with non-small lung cancer brain metastasis were independent factors that have influenced OS.Conclusion. Application of combined therapy for brain metastasis can provide reasonable OS for patients with controlled systemic disease. Using of the cisplatin as a part of combined therapy provide statistically meaningful rise in OS for patients with non-small lung cancer brain metastasis.

Risk factors for 30-day postoperative surgical site hematoma requiring evacuation after resection of brain metastases

ObjectiveTo identify the risk factors for a 30-day postoperative surgical site hematoma requiring evacuation (POH) after surgical resection of brain metastases. MethodsPatients who underwent surgical resection of brain metastases between 2011 and 2019 at our institution were included. Risk factors for a 30-day POH were identified using a multivariate logistic regression model. ResultsA total of 158 patients were included in the analysis. The mean (SD) age of the study population was 59.3 (12.0) years, and 82 (53.2%) patients were female. The incidence of a 30-day POH was 8.2% (13 patients). There was no statistically significant association between the occurrence of a 30-day POH and overall mortality (p = 0.100). On multivariate analysis, there was a statistically significant association between a 30-day POH and younger age (OR=0.91; 95% CI=0.83, 0.99; p = 0.035), higher BMI (OR=1.61; 95% CI=1.16, 2.46; p = 0.010), and blood type AB (OR=21.7; 95% CI=1.66, 522; p = 0.031). On receiver operating characteristic analysis, a threshold BMI of 25.1 kg/m2 and threshold age of 57 gave the optimum balance of sensitivity and specificity in predicting the occurrence of a 30-day POH. ConclusionsPatients below 57 years old, who have a BMI of above 25, and/or have blood type AB were at higher risk of developing a 30-day POH after surgical resection of brain metastases. Additional care in intraoperative hemostasis and postoperative monitoring may be indicated among patients who have these risk factors.

Abstract B032: Immune landscape of resected brain metastases in patients treated with and without immune checkpoint blockade immunotherapy

Abstract Background: The brain metastatic niche has been historically difficult to study and thus poorly understood. Although brain metastases portend high morbidity and mortality, increasing evidence has shown that immune checkpoint blockade (ICB) can confer long-lasting responses in patients. How ICB remodels the brain tumor microenvironment is still relatively unknown. Here, we examine the immune microenvironment of resected brain metastases in a cohort of 19 patients pre-operatively treated with and without ICB using single-cell methods. Methods: Tumor tissue was obtained from patients who underwent surgical resection of brain metastases at our institution, and single-cell RNA sequencing (scRNAseq) and multiplex immunofluorescence (mIF) analyses were performed, including unsupervised clustering and multivariate regression. Results: A total of 8 patients with pre-operative exposure and 11 patients without pre-operative exposure to ICB were included. Represented histologies included melanoma, breast, lung, and endometrial cancers. Basic demographic and clinical characteristics, including age, sex, body mass index, performance status, stage at initial diagnosis, and time from initial diagnosis to development of brain metastases were not significantly different between the two groups. mIF revealed an immune exclusion phenotype in ICB naïve samples compared to ICB-treated samples, manifested by the lower density and percentage of lymphoid infiltrate and presence of immune perivascular cuffing. T cells in the ICB-treated group had higher expression of both effector and exhaustion markers (IFNG, GZMH, PDCD1, HAVCR2, TOX, NR4A2, NR4A1); while myeloid cells exhibited increased interferon-stimulated gene expression (CXCL9, CXCL10, STAT1, GBP1, GBP4, GBP5, MHC-II genes). One particular cluster of CD8+ T cells, the TCF and CD226-expressing progenitor population, correlated with overall survival. Furthermore, ICB-treated samples showed decreased CD14+ CD206+ perivascular macrophages, suggesting that these macrophages play a role in restraining immune cell extravasation and tumor infiltration. Conclusion: This work contributes to the growing understanding of the brain metastatic niche and the impact of ICB on this unique microenvironment. While it is not surprising that we found increased T cell numbers and activation in ICB-treated samples, we also found increased evidence of TIL exhaustion. This may be a result of selection bias, as patients who undergo resection after ICB treatment typically do so due to poor response and intracranial progression, or from chronic antigen stimulation from checkpoint inhibition. Interestingly, our studies suggest that the myeloid populations, particularly the perivascular macrophages, are an important mediator of the brain tumor microenvironment. Further functional studies are needed to investigate the role of these perivascular macrophages and elucidate the cross-talk between these cells, infiltrating lymphocytes, and the brain vasculature. Citation Format: Eileen F. Shiuan, Lu Sun, Jeremy Reynoso, Shanpeng Li, Gang Li, Jiyoon Kim, Won Kim, Robert Prins. Immune landscape of resected brain metastases in patients treated with and without immune checkpoint blockade immunotherapy [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr B032.