Extracranial Metastases Research Articles

EPID-29. EPIDEMIOLOGICAL CHARACTERIZATION OF BRAIN METASTASES IN MELANOMA: A LARGE POPULATION BASED-STUDY FROM 2014-2024

Abstract Brain metastases (BM) are the second most common cause of mortality in metastatic melanoma. Despite increased screening, mortality remains substantial. Additionally, population-based studies of melanoma BM capture only synchronous metastases, therefore up-to-date epidemiological and survival studies may better inform screening and management strategies. Thus, we retrospectively analyzed the TrinetX Oncology dataset to study the prevalence and survival patterns of patients with melanoma BM. Data from 13,505 patients with histologically-confirmed melanoma was extracted. Demographic and clinical parameters were compared between patients with and without BM via t-test and chi-squared analysis. Overall survival (OS) was evaluated using Kaplan-Meier and Cox regression analyses after cohorts were propensity-matched for age, sex, race, ethnicity, stage, extracranial metastases, excision of skin lesions, radiation, and antineoplastic utilization. In our study, the prevalence of BM was 7.3% (9.2% precocious, 22.5% synchronous, 68.3% metachronous). Compared to patients without BM, patients who developed BM were more often male (p<0.0001), non-Hispanic (p<0.0001), White (p<0.02), and presented with advanced-stage disease (p<0.0001). Patients with unspecified malignant melanoma (p<0.0001) and nodular melanoma (p<0.0001) were more likely to develop BM compared to those with other histological subtypes. Additionally, patients with BM were more likely to have ulceration (p<0.0001) and extracranial metastases (p<0.0001). Skin excision procedures were less common in patients with BM (p<0.0001), whereas radiotherapy and antineoplastics were more common. When assessed from melanoma diagnosis, patients who developed BM any time along their disease course had reduced OS (HR(95% CI): 2.265(1.934-2.653)). When assessed from metastatic onset, patients with BM had reduced OS compared to those with only extracranial metastases (HR (95% CI): 2.197(1.883-2.563)). Synchronous BM were associated with decreased OS compared to metachronous BM when assessed from melanoma onset (HR(95% CI): 0.6(0.442-0.815)), but there was no survival difference after BM development. In conclusion, BMs decrease OS in melanoma. Our findings may inform screening and management of patients at risk for melanoma BM.

NCMP-18. A CASE OF METASTATIC GLIOBLASTOMA MULTIFORME

Abstract Glioblastoma multiforme (GBM) is the most common primary brain tumor and rarely causes metastasis. We present a case of a 43-year-old female who developed tingling and heaviness in her right lower extremity in March 2023. This sensation progressed to involve her entire right hemi-body over the next two months. She presented to the emergency department where an MRI show a large left frontal parietal mass measuring 5.2x3.7x3.7cm with significant mass effect. She underwent surgical resection and surgical pathology showed IDH1-mutant R132H, retained ATRX, MGMT promoter mutation, and ki-67 of 80%. She received 6 weeks chemoradiation and then started maintenance temozolomide at 150mg/m2. Temozolomide was increased to 200mg/m2 for cycle 3 maintenance. In March 2024, she presented to the hospital with pain radiating down her legs and saddle anesthesia. MRI lumbar spine showed infiltrating osseous mass at S1 and S2 and bilateral sacral ala with anterior and posterior extraosseous invasion, invading the spinal canal resulting in moderate to severe spinal canal narrowing and compression of the sacral nerve roots. She underwent biopsy of the lesion which showed IDH wildtype metastatic GBM. She also underwent lumbar puncture and cerebrospinal fluid cytology was negative. She experienced pancytopenia limiting chemotherapy options. In April 2024, she underwent PET scan which showed hypermetabolic epidural soft tissue in spinal canal at L5-S1 level, widespread hypermetabolic skeletal lesions, tiny left cervical level 4 lymph node, small hypermetabolic right hilar, aortocaval, left retroperitoneal nodes and a tiny left common iliac node. The incidence of extracranial metastasis is 0.4-2.0% with less than 25 reported cases of bone marrow spread. This is thought to be rare due to the absence of lymphatics within the brain and the limited survival associated with GBM. This metastasis may occur through vascular invasion, perineural spread, lymphatics, direct invasion, or iatrogenic spread into soft tissues.

RADT-29. ASSOCIATION OF ANATOMIC PROXIMITY OF BRAIN PARENCHYMAL METASTASIS TO THE CSF SPACE AND UPFRONT STEREOTACTIC RADIOSURGERY TO SUBSEQUENT LEPTOMENINGEAL METASTASIS DEVELOPMENT IN BRAIN METASTATIC NSCLC

Abstract OBJECTIVE The most common solid systemic malignancies that metastasize to the leptomeninges are lung cancer, especially non-small cell lung cancer (NSCLC). Generally, patients develop leptomeningeal metastasis (LM) subsequent to brain parenchymal metastases (BM). However, its predictors remain unknown. Hence, the present study was carried out to explore the predictors of LM in brain metastatic NSCLC patients. METHODS The final analysis included 112 pathologically definite NSCLC patients with BMs treated in our center between July 1, 2014, and December 30, 2020. Of 112, one-half had LM. Three radiologists analyzed radiologic images independently. Anatomic proximity of BMs to the CSF space (dural-based metastases, periventricular or major CSF cisterns such as basal cisterns and cisterna magna) was measured and stratified into CSF space invading/bordering and detached lesions. The endpoint was the occurrence of LM or death, whichever occurred first. Univariable and multivariable logistic regressions were performed to identify potential predictors for LM. RESULTS Of 112, 48 (42.8%) were males, and 64 (57.2%) were females. Most patients (90.2%) had adenocarcinoma histology. The median follow-up time was 10.1 months (IQR, 4.2-18.4 months) following BM diagnosis. Univariate logistic regression analysis demonstrated that histology (OR 0.084, 95%CI 0.004-0.461, P=0.020), EGFR/ALK/ROS1 mutation (OR 3.868, 95%CI 1.583-10.079, P=0.003), CSF space invading/bordering lesion (OR 10.278, 95%CI 4.203-27.375, P=0.000), extracranial metastasis control (OR 2.7, 95%CI 1.191-6.309, P=0.019), upfront stereotactic radiosurgery (SRS) (OR 0.024, 95%CI 0.001-0.12, P=0.000), and target therapy (OR 4.476, 95%CI 1.877-11.464, P=0.001) were the potential predictor. CSF space invading/bordering lesion (OR 7.443, 95%CI 2.099-32.853, P=0.003) and upfront SRS (OR 0.035, 95%CI 0.002-0.212, P=0.003) remained statistically significant in the multivariate logistic regression analysis. CONCLUSION CSF space invading/bordering BMs may increase the risk of LM development in brain metastatic NSCLC patients, while upfront SRS targeting BM potentially decreases the risk. A prospective study is warranted to affirm.

Differential T cell accumulation within intracranial and subcutaneous melanomas is associated with differences in intratumoral myeloid cells

Patients with metastatic brain melanomas (MBM) experience shorter-lasting survival than patients with extracranial metastases, and this is associated with a higher fraction of dysfunctional CD8 T cells. The goal of this study was to understand the underlying cause of T cell dysfunction in MBM. To accomplish this, we compared murine B16 melanomas implanted intracranially (IC) or subcutaneously (SC). CD8 T cell activation was not altered, but representation in IC tumors was lower. Transferred activated or naïve CD8 T cells accumulated in similar numbers in both tumors, suggesting that the vasculature does not differentially impair T cell presence. Surprisingly, we found no evidence for T cell activation in draining lymph nodes of SC or IC tumor-bearing mice, consistent with the fact that dendritic cells (DC) that had acquired tumor antigen showed an immature phenotype. Instead, T cell activation occurred within both tumors, where the majority of tumor antigen+ myeloid cells were found. While, the numbers of intratumoral DC were comparable, those in IC tumors acquired less tumor antigen, and were alternatively matured based on upregulation of MHCII without upregulation of CD86. Additionally, in IC tumors, the largest population of tumor antigen+ myeloid cells were microglia. However, their presence did not influence either antigen acquisition or the phenotype of other myeloid cell populations. Overall, our data suggest that diminished representation of CD8 T cells in IC tumors is a consequence of alternatively matured DC and/or microglia that induce distinctly activated T cells, which ultimately fail to continue to accumulate inside the tumor.

Influence of brain metastases on the classification, treatment, and outcome of patients with extracranial oligometastasis: a single-center cross-sectional analysis

Background and introductionIncreasing evidence suggests that a subgroup of patients with oligometastatic cancer might achieve a prolonged disease-free survival through local therapy for all active cancer lesions. Our aims are to investigate the impact of brain metastases on the classification, treatment, and outcome in these patients.Materials and methodsWe analyzed a total of 7,000 oncological positron emission tomography scans to identify patients with extracranial oligometastatic disease (defined as ≤ 5 intra- or extra-cranial metastases). Concurrent magnetic resonance imaging brain was assessed to quantify intracranial tumor burden. We investigated the impact of brain metastases on oligometastatic disease state, therapeutic approaches, and outcome. Predictors for transitioning from oligo- to polymetastatic states were evaluated using regression analysis.ResultsA total of 106 patients with extracranial oligometastases and simultaneous brain metastases were identified, primarily originating from skin or lung/pleura cancers (90%, n = 96). Brain metastases caused a transition from an extracranial oligometastatic to a whole-body polymetastatic state in 45% (n = 48) of patients. While oligometastatic patients received systemic therapy (55% vs. 35%) more frequently and radiotherapy for brain metastases was more often prescribed to polymetastatic patients (44% vs. 26%), the therapeutic approach did not differ systematically between both sub-groups. The oligometastatic sub-group had a median overall survival of 28 months compared to 10 months in the polymetastatic sub-group (p < 0.01).ConclusionIn patients with brain metastases, a low total tumor burden with an oligometastatic disease state remained a significant prognostic factor for overall survival. Presence of brain metastases should therefore not serve as exclusion criterion for clinical trials in the field of oligometastatic disease. Moreover, it underscores the importance of considering a multimodality treatment strategy in oligometastatic cancer patients.

P17.01.A ANAMNESTIC RADIOLOGICAL METASTASES OUTCOME SURGICAL SCORE (ARMO-S). A PURPOSE OF A PREDICTIVE SCORING SYSTEM FOR SURGICAL BRAIN METASTASES

Abstract BACKGROUND Several risk stratification scores have been suggested to aid prognostication and guide treatment strategies for brain metastases (BMs). However, the current scores do not focus on the specific neurosurgical population, therefore not predicting short-term mortality and postoperative performance status. MATERIAL AND METHODS This retrospective observational study of 362 consecutive patients treated with surgery for BMs aims to identify the factors associated with post-surgical outcomes and propose a surgery-specific prognostic score for patients with BMs candidate for open surgery. RESULTS Factors significantly associated with OS and performance status in multivariate analysis were age, KPS, surgical site, synchronous debut of BM, number, tumor volume, seizure, extra-cranial metastases, and deep-seated location. The variables were incorporated into the Anamnestic Radiological Metastases Outcome Surgical score (ARMO-S). The values range between 0 and 10. Patients were divided into two groups (low-risk and high-risk) based on each significant subgroup’s median survival and performance status with an optimal cutoff value determined as 4. The two groups have significant differences in OS (9.6 versus 14 months, p = 0.0048) postoperative KPS (90 versus 70, p=0.012) and KPS at last follow-up evaluation (75 versus 30, p&amp;lt;0.001) CONCLUSION ARMO-S is a simple and comprehensive score for BM patients selected for neurosurgery, as it incorporates the main factors of the most important prognostic scores, implementing them with more surgery-specific predictive elements such as tumor location and volume, presence of seizures at onset, and involvement of eloquent brain areas.

Prevalence, treatment patterns, and survival of patients with brain metastases from small cell lung cancer: A retrospective study using the TriNetX Oncology Database

Abstract Background Brain metastases (BM) portend increased morbidity and mortality in patients with small cell lung cancer (SCLC). We aimed to characterize the prevalence, timing, treatment patterns, and survival outcomes of BM associated with SCLC over the past decade. Methods Data from 4014 patients with histologically confirmed SCLC were extracted from the TriNetX Oncology database. Clinical and demographic variables were compared between patients with and without BM using Chi-squared and t-tests. Kaplan–Meier and Cox regression analyses were used to evaluate overall survival (OS), after propensity score matching cohorts for age at diagnosis, sex, cancer stage at diagnosis, extracranial metastases, and cancer-directed therapy. Results Among 4014 patients with SCLC, 35.0% had BM (9.9% synchronous, 21.2% metachronous, 3.9% precocious). Patients who developed BM were younger (P &amp;lt; .001) at SCLC diagnosis, more likely Black/African American (P = .0068), and presented with more advanced cancer stages (P &amp;lt; .001) than patients who did not develop BM. The median BM-free survival from the time of SCLC diagnosis was 27.9 months. Patients with BM received higher rates of cancer-directed therapies than those without BM. Synchronous BM was associated with lower OS than metachronous BM after the diagnosis of SCLC (HR[95% CI] = 1.56[1.32–1.83]), but there was no difference in OS after the BM diagnosis. OS did not differ between patients with BM and patients with extracranial metastases only, following the diagnosis of metastatic disease. Conclusions Our findings support that independently of the chronicity of BM diagnosis, patients with SCLC have poor survival once the diagnosis of BM is conferred.

Development of graded prognostic assessment for breast Cancer brain metastasis incorporating extracranial metastatic features: a retrospective analysis of 284 patients

BackgroundBreast cancer brain metastasis (BCBM) is associated with poor survival outcomes and reduced quality of life. The Graded Prognostic Assessment (GPA) score model serves as a well-established tool for predicting the prognosis of BCBM. Notably, the presence of extracranial metastasis (ECM) is considered as a significant prognostic factor in the breast GPA model. This study aims to further refine other features of ECM to enhance the prognostic prediction for BCBM.MethodsThis study included all inpatients diagnosed with BCBM at the Cancer Hospital, Chinese Academy of Medical Sciences, from January 2010 to July 2021. Baseline characteristics of patients were compared based on features of ECM, including the presence, number, location, and control status of metastases. Overall survival (OS) were compared using the Kaplan–Meier method with log-rank tests. Cox regression analyses were conducted to identify significant prognostic factors. The aforementioned ECM features were incorporated into the original Breast-GPA model to enhance its prognostic accuracy. The concordance index (C-index) and restricted mean survival time (RMST) were utilized to evaluate and compare the predictive accuracy of the updated and original survival models.Results284 patients with BCBM were included in the study. Kaplan–Meier survival curves suggested that patients without ECM when diagnosed with BCBM showed better survival (p = 0.007). In the subgroups with ECM, more than 3 organs involved, both bone and visceral metastasis and progressive ECM portended dismal OS (p = 0.003, 0.001 and <0.001). Multivariate analysis demonstrated that molecular subtype, presence of ECM, and number of brain metastasis significantly influenced OS after BCBM. By modifying the current GPA model to include more precise characteristics of ECM, the predictive accuracy was further enhanced as indicated by the C-index and RMST curve.ConclusionsMore ECM sites, both bone and visceral invasion and uncontrolled ECM were dismal prognostic factors for survival outcomes of BCBM patients. A new Breast-GPA model with better predictive effect was constructed.

Clinicopathologic and genomic features associated with brain metastasis after resection of lung adenocarcinoma

ObjectiveTo identify clinicopathologic and genomic features associated with brain metastasis after resection of lung adenocarcinoma (LUAD) and to evaluate survival after brain metastasis. MethodsPatients who underwent complete resection of stage I-IIIA LUAD between 2011 and 2020 were included. A subset of patients had broad-based panel next-generation sequencing performed on their tumors. Fine-Gray models for the development of brain metastasis were constructed, with death without brain metastasis as a competing risk. ResultsA total of 2660 patients were included. The median duration of follow-up was 71 months (95% confidence interval [CI], 69-73 months). The cumulative incidence of brain metastasis at 10 years was 9.8%. Among patients who developed a brain metastasis, the median time from surgery to brain metastasis was 21 months (interquartile range, 10-42 months). Higher maximum standardized uptake value of the primary tumor, neoadjuvant therapy, lymphovascular invasion, and stage III disease were associated with the development of brain metastasis. Among patients who underwent next-generation sequencing, a multivariable analysis identified neoadjuvant therapy, pathologic stage, and TP53 mutations as associated with development of brain metastasis. The median survival after brain metastasis was 18 months (95% CI, 13-24 months). Better performance status, lack of extracranial metastasis, stereotactic radiosurgery, and targeted therapy were associated with better survival after brain metastasis. ConclusionsBrain metastasis is common after complete resection of LUAD and often occurs within 2 years. Markers of aggressive tumor biology, including higher maximum standardized uptake value, lymphovascular invasion, and TP53 mutations, and neoadjuvant therapy are associated with brain metastasis.

Predictive Factors for Long-Term Disease Control in Systemic Treatment-Naïve Oligorecurrent Renal Cell Carcinoma Treated with Up-Front Stereotactic Ablative Radiotherapy (SABR).

Stereotactic ablative radiotherapy (SABR) is emerging as a potential local treatment option for oligometastatic RCC. This study aims to evaluate the efficacy of SABR in patients with oligorecurrent RCC. A total of 50 patients with histologically confirmed RCC underwent SABR for oligorecurrence between 2006 and 2022. Eligible patients had up to five extracranial metastases and were systemic treatment-naïve at the time of irradiation. The primary endpoints of the analysis were overall survival (OS), local control (LC), distant metastasis-free survival (DMFS), and time to systemic therapy initiation. The median OS was not reached, with 1- and 3-year OS rates of 93.8% and 77.5%, respectively. LC rates at one and three years were 95.8% and 86.5%, respectively. The median time to systemic therapy initiation was 63.8 months, and the median DMFS was 17.9 months, with one- and three-year rates of 63.4% and 36.6%, respectively. Multiple metastases were a negative predictive factor for DMFS (HR 2.39, p = 0.023), whereas lung metastases were associated with a more favorable outcome (HR 0.38, p = 0.011). SABR offers a valuable treatment option for oligometastatic RCC, demonstrating significant potential for achieving long-term disease control and delaying the need for systemic therapy.

Outcome of whole brain irradiation with a dose-escalated simultaneous-integrated boost in patients with multiple large and/or diffuse brain metastases: real live data and review of the literature

BackgroundWe retrospectively investigate feasibility and safety of whole brain radiotherapy (WBRT) including a simultaneous-integrated boost technique (WBRT-SIB) in a cohort of patients with a very poor prognosis suffering from multiple and/or large brain metastases, unfavorable primary histology, poor performance status and/or symptomatic BMs.Materials and MethodsThirty-five patients with high brain tumor burden, extracranial metastases and low life-expectancy were treated with WBRT-SIB mostly with 35-42 Gy/14 fractions. All metastases were boosted in patients with up to 12 BMs. In patients with > 12 BM, large and/or small metastases in critical brain regions were boosted up to a maximum of 12 SIB volumes.ResultsThe median number of BM was 8 (range 2–45) and the median BM diameter was 12 mm (range 4–90 mm). Fifteen (43%) patients had ≥ 10 BMs and 25 patients presented with a Karnofski index ≤ 80%. Primary tumor histology was NSCLC (n = 13), SCLC (n = 11), breast cancer (n = 7), melanoma (n = 2), other (n = 2). The median iPFS was not reached, and 12- and 18-months iPFS were 75% and 50%, respectively. Overall, seven patients had intracranial progression: two patients within the SIB and WBRT area, one patient only within the SIB region and four patients had new BMs in the WBRT volume alone. The median iPFS for non-SCLC patients was 17 months and the 12- and 18-month iPFS were 56.8% and 28.4%, respectively. There was no significant OS difference between SCLC-group and non-SCLC patients (p = 0.38). Overall, median OS was 8.7 months and 1-year OS was 25%. The treatment was generally well-tolerated with no observed cases of radionecrosis.ConclusionOur WBRT-SIB approach involves a combination of whole brain radiotherapy and a simultaneous integrated boost to specific tumor volumes, and its effectiveness is compared with other treatment modalities in the literature. Further research, including prospective studies with larger patient cohorts, is necessary to validate and refine the findings.

Metastatic Malignant Melanoma of Brain: A Rare Case Report

AbstractMalignant melanoma is third most common cause of brain metastasis after lung and breast cancer. Most patients with brain metastases from malignant melanoma are diagnosed after treatment for known extracranial metastases and have a poor outcome despite various local and systemic therapeutic approaches. Here we discuss an unusual case of a 61-year-old male patient who presented with a brain metastasis as the initial disease presentation and the presumed primary lesion was later found in the gastrointestinal tract and the scalp. Treatment consisted of a surgical removal of the large intracranial lesion. Further evaluation for primary lesion was done by general physical examination, contrast-enhanced computed tomography (CECT) of the chest and whole abdomen. Apart from that, colonoscopy was done, and a biopsy was taken from a suspicious colonic lesion. The scalp pigmented lesion was also evaluated. Both biopsies were in favor of melanoma. Recently, management of metastatic melanoma of the brain is decided according to the number of lesions, accessibility, visceral metastasis, and resectability of the lesion. Various treatment options are surgical resection, whole brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS). Malignant melanoma is relatively radioresistant, so the results are debatable. In conclusion, the prognosis of intracranial malignant melanoma is determined by the following factors: (1) the type of lesion; (2) the involvement of the leptomeninges; (3) the extent of tumor excised; and (4) the molecular immunology borstel number 1 (MIB 1) antibody index, which is the most relevant factor for prognosis in this type of cancer.

Effects of brain radiotherapy strategies on survival in the era of MRI for patients with limited stage small cell lung cancer

Background and purposeIn the context of the widespread availability of magnetic resonance imaging (MRI) and aggressive salvage irradiation techniques, there has been controversy surrounding the use of prophylactic cranial irradiation (PCI) for small-cell lung cancer (SCLC) patients. This study aimed to explore whether regular brain MRI plus salvage brain irradiation (SBI) is not inferior to PCI in patients with limited-stage SCLC (LS-SCLC).MethodsThis real-world multicenter study, which was conducted between January 2014 and September 2020 at three general hospitals, involved patients with LS-SCLC who had a good response to initial chemoradiotherapy and no brain metastasis confirmed by MRI. Overall survival (OS) was compared between patients who did not receive PCI for various reasons but chose regular MRI surveillance and followed salvage brain irradiation (SBI) when brain metastasis was detected and patients who received PCI.Results120 patients met the inclusion criteria. 55 patients received regular brain MRI plus SBI (SBI group) and 65 patients received PCI (PCI group). There was no statistically significant difference in median OS between the two groups (27.14 versus 33.00 months; P = 0.18). In the SBI group, 32 patients underwent whole brain radiotherapy and 23 patients underwent whole brain radiotherapy + simultaneous integrated boost. On multivariate analysis, only extracranial metastasis was independently associated with poor OS in the SBI group.ConclusionThe results of this real-world study showed that MRI surveillance plus SBI is not inferior to PCI in OS for LS-SCLC patients who had a good response to initial chemoradiotherapy.

The indication of palliative whole-brain radiotherapy for patients with brain metastases: a simple prognostic scoring system in the era of stereotactic radiosurgery

BackgroundStereotactic irradiation has become the mainstay treatment for brain metastases (BM), and whole-brain radiotherapy (WBRT) is often used for symptom palliation. However, the survival time of patients with BM undergoing palliative WBRT (pWBRT) is limited, making it difficult to select patients who should receive treatment.MethodsWe collected patient data from 2016 to 2022 at the Shizuoka Cancer Center and retrospectively analyzed the factors related to survival time. Overall survival (OS) was defined as the survival time after WBRT.ResultsA total of 301 patients (median age, 66 years) who underwent pWBRT were included. The primary cancers were lung, breast, gastrointestinal tract, and other cancers in 203 (67%), 38 (13%), 33 (11%), and 27 (9%) patients, respectively. Median OS of all patients was 4.1 months. In the multivariate analysis, male sex (hazard ratio [HR]:1.4), Karnofsky Performance Status (KPS) ≤ 60 (HR:1.7), presence of extracranial metastasis (ECM) (HR:1.6), neutrophil-lymphocyte ratio (NLR) ≥ 5 (HR:1.6), and lactate dehydrogenase (LDH) ≥ upper limit of normal (ULN) (HR:1.3) were significantly associated with shorter OS (all P < 0.05). To predict the OS, we created a prognostic scoring system (PSS). We gave one point to each independent prognostic factor. Median OS for patients with scores of 0–2, 3, and 4–5 were 9.0, 3.5 and 1.7 months, respectively (P < 0.001).ConclusionsMale sex, KPS ≤ 60, presence of ECM, NLR ≥ 5, and LDH ≥ ULN were poor prognostic factors for patients with BM undergoing pWBRT. By PSS combining these factors, it may be possible to select patients who should undergo pWBRT.

Clinicogenomic predictors of survival and intracranial progression after stereotactic radiosurgery for colorectal cancer brain metastases.

Brain metastases (BM) from colorectal cancer (CRC) are associated with dismal prognosis. When BM-directed therapy is considered, better methods are needed to identify patients at risk of poor oncological outcomes in order to optimize patient selection for closer surveillance or escalated therapy. The authors sought to identify clinicogenomic predictors of survival and intracranial disease progression after CRC BM have been treated with stereotactic radiosurgery (SRS). Patients with newly diagnosed CRC BM treated with SRS between 2009 and 2022 who had next-generation genomic sequencing data available were included. Frameless SRS was delivered in 1-5 fractions, alone or after neurosurgical resection. Outcomes included overall survival (OS) and intracranial progression (IP), evaluated per patient treated with SRS, and local progression (LP), evaluated per BM. Associations between baseline clinicogenomic features and outcomes were evaluated with Cox regression and competing risk regression, with death as a competing risk. This analysis included 123 patients with 299 BM. At BM diagnosis, 111 patients (90%) had progressive extracranial disease, and 79 patients (64%) had ≥ 3 sites of extracranial metastasis. The median (IQR) number of BM was 2 (1-3) per patient. The median (IQR) biologically effective dose (BED) was 51.3 (51.3-65.1) Gy, corresponding to a prescription of 27 Gy in 3 fractions. OS, IP, and LP estimates at 1 year after SRS were 36%, 55%, and 12%, respectively. OS was independently associated with progressive extracranial disease (HR 4.26, 95% CI 1.63-11.2, p = 0.003) and ≥ 3 extracranial metastatic sites (HR 1.84, 95% CI 1.12-3.01, p = 0.02). LP was less likely when BM received BED ≥ 51.3 Gy (HR 0.24, 95% CI 0.07-0.78, p = 0.02), independent of BM diameter (HR 1.21/cm, 95% CI 0.8-1.84, p = 0.4). IP was independently associated with genomic alterations; TP53 driver alterations were associated with higher risk of IP (HR 2.71, 95% CI 1.26-5.79, p = 0.01), whereas MYC pathway alterations were associated with lower risk (HR 0.15, 95% CI 0.03-0.68, p = 0.01). The authors identified clinicogenomic features associated with adverse outcomes after SRS for CRC BM. Progressive and extensive extracranial metastases predicted worse OS. Insufficient SRS doses predicted greater risk of LP. Wild-type TP53 and alterations in the MYC pathway were independently associated with lower risk of IP. Patients at high risk of IP may be considered for closer surveillance or escalated therapy.

Extracranial metastatic oligodendroglioma with molecular progression, case presentation

BackgroundExtraneural metastasis of central nervous system tumors is generally rare and most often reported in glioblastomas and medulloblastomas, whereas oligodendrogliomas seem to have the lowest risk of extracranial metastasis. Given its infrequent occurrence, both the diagnosis and therapy of metastatic oligodendroglioma is often challenging.Case presentationThis case study presents an oligodendroglioma, the isocitrate dehydrogenase 1 (IDH1) mutant, 1p/19q-codeleted tumor with bone marrow metastasis. The significance of this case lies in the comprehensive molecular analysis conducted for both the primary tumor and the metastasis. Chromosome 7 trisomy and chromosome 10 monosomy (+ 7/-10) were detected in the metastasis indicating molecular progression, which, to the best of our knowledge, has not been previously documented in metastatic oligodendroglioma.ConclusionsThis case study serves additional information for better understanding of the metastatic capabilities of CNS tumors.

External validation of the lung-molGPA to predict survival in patients treated with stereotactic radiotherapy for brain metastases of non-small cell lung cancer

BackgroundIn the era of personalized medicine, individualized prognostic models with tumor characteristics are needed to inform patients about survival. Before clinical use, external validation of such models by an independent group is needed. An updated version of the graded prognostic assessment (GPA) estimates survival in patients with brain metastases (BMs) of non-small cell lung cancer (NSCLC). This is the first external validation of the updated Lung-molGPA in patients treated with stereotactic radiotherapy (SRT) for one or more BMs. Materials and methodsPatients treated with SRT for BMs from NSCLC adenocarcinoma were retrospectively included. GPA score was calculated for each patient based on six prognostic factors including age, Karnofsky Performance Status, number of BMs, extracranial metastases, EGFR/ALK status, and PD-L1 expression. Kaplan-Meier analysis evaluated survival probability. Impact of individual prognostic factors on survival was assessed by univariate and multivariate analyses using the Cox proportional hazard model. Predictive performance was evaluated using discrimination (C-statistic) and calibration (Brier test). ResultsThe cohort (n = 241) was divided into four prognostic groups. Overall median survival was 15 months. Predicted and observed median survival were similar between the original and validation cohorts, apart from the most favorable prognostic group. With adequate C-statistics and Brier scores, the Lung-molGPA provided accurate survival predictions. ConclusionThe Lung-molGPA accurately predicted survival in our European population, except for an overestimation of survival in the small most favorable prognostic group. This prognostic model was externally validated and is therefore useful for counseling of patients with BMs of NSCLC adenocarcinoma.

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.

Expanding multiple features of extracranial metastasis to predict survival for patients with breast cancer brain metastasis: A population-based retrospective analysis.

e13038 Background: Breast cancer brain metastasis (BCBM) is associated with poor survival outcomes and reduced quality of life. The Graded Prognostic Assessment (GPA) score model serves as a well-established tool for predicting the prognosis of BCBM. Notably, the presence of extracranial metastasis (ECM) is considered as a significant prognostic factor in the breast GPA. This study aims to further refine this factor to enhance the prognostic prediction for BCBM. Methods: This study included all inpatients diagnosed with BCBM at the Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS), from January 2010 to July 2021. The subsets were categorized by the presence, number, location, and control status of ECM. Baseline clinicopathological characteristics were documented and compared among subgroups. The primary endpoint was overall survival (OS) after the diagnosis of BCBM. We used the Kaplan–Meier method with log-rank test to compare the survival outcomes. Cox regression analyses were conducted to identify significant prognostic factors, which were then incorporated into a new Breast-GPA model. Results: A total of 286 patients with BCBM were included in the study. Kaplan–Meier survival curves suggested that patients without ECM when diagnosed with BCBM showed better survival (p=0.0068). In the subgroups with ECM, more than 3 organs involved, both bone and visceral metastasis and progressive ECM portended dismal OS (p=0.0032, 0.0014 and 0.00054). Multivariate analysis (MVA) demonstrated that the presence, number, and control status of ECM significantly influenced OS after BCBM (p=0.01, 0.03, and 0.048, respectively). The specific location of ECM also had a significant impact on the long-term survival (p=0.0014). By modifying the current GPA model to include categories for '3 or fewer controlled ECM', the predictive accuracy of the newly established GPA model was further enhanced. Conclusions: More extracranial sites, both bone and visceral invasion and uncontrolled ECM were independent prognostic factors for dismal survival outcomes of BCBM patients.

Diagnosis and genetic characterization of CNS metastases in lung cancer via shallow whole-genome sequencing of CSF cell-free DNA.

e14013 Background: The genetic characterization of CNS metastases in lung cancer is hindered by the limited sampling opportunities and genetic heterogeneity between intracranial and extracranial lesions. To address these challenges, this study uses cerebrospinal fluid (CSF) and blood samples, to detect and characterize CNS metastasis variants through shallow whole-genome sequencing (sWGS). Methods: From Dec. 2021 to Aug. 2023, 57 lung cancer patients were recruited, comprising 29 with leptomeningeal metastases (LMs) and 28 with only parenchymal brain metastases (PMs). A total of 66 blood and 112 CSF samples were collected for cfDNA sWGS to analyze chromosomal arm CNVs, focal amplifications (CN &gt; 5) and SNV/InDels. Cytology was also conducted on 95 of these CSF samples. Variant differences between PMs and extracranial metastases (EMs) were analyzed using the MSK-MET database. Results: CSF cfDNA concentration was significantly lower than that in plasma (p &lt; 0.0001), with 41.7% of samples unquantifiable, yet all samples successfully completed sWGS. The cfDNA tumor fraction in CSF was significantly higher than in paired plasma (p &lt; 0.0001), and most arm CNVs and gene amplifications exclusively detected in CSF. Cytology, as the gold standard for LM diagnosis, had a sensitivity of 0.76. The sensitivity for LM diagnosis based on aneuploidy and genomic amplification fraction (GAF) were 0.51 and 0.80, respectively, without compromising specificity. Gains in 1p, 7p, 11q, 16p, and 17q, as well as losses in 9p and 9q, were significantly more frequent in PMs compared to EMs and further increased in the LMs (p &lt; 0.05). Notably, losses in 1p, 4p, 5q, and 11p, significantly more frequent in PMs than in extracranial metastases, but showed a significant increase in gain frequency in LMs (p &lt; 0.05). In the LM group, the frequency of EGFR L858R and amplification of nearly the entire 7p where the EGFR located, were significantly increased, whereas KRAS G12D frequency significantly decreased (p &lt; 0.05). Conclusions: The characteristics of extremely low concentration but high tumor fraction of CSF cfDNA make it suitable for sWGS, enhancing LM diagnostic sensitivity without compromising specificity, and identifying molecular characteristics of CNS metastasis. These molecular features require further validation in larger prospective clinical cohorts, offering potential for personalized diagnosis and treatment of CNS metastases.