Presence Of Extracranial Metastases Research Articles

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.

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.

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.

Brain metastases: Comparing clinical radiological differences in patients with lung and breast cancers treated with surgery

PurposeBrain metastases (BMs) most frequently originate from the primary tumors of the lung and breast. Survival in patients with BM can improve if they are detected early. No studies attempt to consider all potential surgical predictive factors together by including clinical, radiological variables for their recognition. MethodsThe study aims to simultaneously analyze all clinical, radiologic, and surgical variables on a cohort of 314 patients with surgically-treated BMs to recognize the main features and differences between the two histotypes. ResultsThe two groups consisted of 179 BM patients from lung cancer (Group A) and 135 patients from breast cancer (Group B). Analysis showed that BMs from breast carcinoma are more likely to appear in younger patients, tend to occur in the infratentorial site and are frequently found in patients who have other metastases outside of the brain (46 %, p = 0.05), particularly in bones. On the other hand, BMs from lung cancer often occur simultaneously with primitive diagnosis, are more commonly cystic, and have a larger edema volume. However, no differences were found in the extent of resection, postoperative complications or the presence of decreased postoperative performance status. ConclusionThe data presented in this study reveal that while the two most prevalent forms of BM exhibit distinctions with respect to clinical onset, age, tumor location, presence of extra-cranial metastases, and lesion morphology from a strictly surgical standpoint, they are indistinguishable with regard to outcome, demonstrating comparable resection rates and a low risk of complications.

Prognosis versus Actual Outcomes in Stereotactic Radiosurgery of Brain Metastases: Reliability of Common Prognostic Parameters and Indices.

This study aims to evaluate the clinical outcome of stereotactic radiosurgery as the sole treatment for brain metastases and to assess prognostic factors influencing survival. A total of 108 consecutive patients with 213 metastases were retrospectively analyzed. Treatment was determined with close-meshed MRI follow-up. Various prognostic factors were assessed, and several prognostic indices were compared regarding their reliability to estimate overall survival. Median overall survival was 15 months; one-year overall survival was 50.5%. Both one- and two-year local controls were 90.9%. The rate of new metastases after SRS was 49.1%. Multivariate analysis of prognostic factors revealed that the presence of extracranial metastases, male sex, lower KPI, and progressive extracranial disease were significant risk factors for decreased survival. Of all evaluated prognostic indices, the Basic Score for Brain Metastases (BSBMs) showed the best correlation with overall survival. A substantial survival advantage was found for female patients after SRS when compared to male patients (18 versus 9 months, p = 0.003). SRS of brain metastasis is a safe and effective treatment option when frequent monitoring for new metastases with MRI is performed. Common prognostic scores lack reliable estimation of survival times. Female sex should be considered as an additional independent positive prognostic factor influencing survival.

Analysis of prognostic factors and the role of epilepsy in neurosurgical patients with brain metastases.

Brain metastases (BMs) represent the most frequent brain tumors in adults. The identification of key prognostic factors is essential for choosing the therapeutic strategy tailored to each patient. Epilepsy can precede several months of other clinical presentations of BMs. This work aimed to study the impact of epilepsy and other prognostic factors on BMs patients' survival. This retrospective study included 51 patients diagnosed with BMs and who underwent neurosurgery between 2010 and 2021. The impact of BM features and patient's clinical characteristics on the overall survival (OS) was analyzed through uni- and multivariate analysis. The average OS was 25.98 months and differed according to the histology of the primary tumor. The primary tumor localization and the presence of extracranial metastases had a statistically significant impact on the OS, and patients with single BM showed a superior OS to those with multifocal lesions. The localization of BMs in the temporal lobe correlated with the highest OS. The OS was significantly higher in patients who presented seizures in their clinical onset and in those who had better post-surgical Karnofsky performance status, no post-surgical complications, and who underwent post-surgical treatment. Our study has highlighted prognostically favorable patient and tumor factors. Among those, a clinical onset with epileptic seizures can help identify brain metastasis hitherto silent. This could lead to immediate diagnostic-therapeutic interventions with more aggressive therapies after appropriate multidisciplinary evaluation.

Non-small cell lung cancer with synchronous brain metastases: Identification of prognostic factors in a retrospective multicenter study (HOT 1701).

Non-small-cell lung cancer (NSCLC) is associated with a high incidence of brain metastasis (BM), and the prognosis of patients with NSCLC and BM is poor. This study aimed to identify the prognostic factors and elucidate the survival rates of Japanese patients with NSCLC and BM at initial diagnosis. HOT 1701 is a retrospective multicenter study of patients with NSCLC and BM at initial diagnosis. The medical records of all consecutive patients diagnosed with advanced or recurrent NSCLC and BM at 14 institutions of the Hokkaido Lung Cancer Clinical Study Group Trial (HOT) in Japan were reviewed. The participants were categorized based on the presence or absence of driver mutations. The Kaplan-Meier method was used to estimate median overall survival (OS). Univariate and multivariate analyses were performed to identify prognostic factors in these patients. Among 566 patients with NSCLC and BM, the median OS was 11.8 months. Patients with driver mutations survived longer than those without driver mutations. The univariate and multivariate analyses revealed 6 independent prognostic factors: age ≥65 years, poor performance status, T factor, absence of driver gene mutations, presence of extracranial metastases, and number of BM. According to the prognostic score based on these 6 factors, the patients were stratified into 3 risk groups: low-, intermediate-, and high-risk, with median OS of 27.8, 12.2, and 2.8 months, respectively. We developed a new prognostic model for patients with NSCLC and BM, which may help determine prognosis at diagnosis.

P13.06.A RADIOMIC FEATURES FOR RISK-STRATIFICATION IN PATIENTS WITH BRAIN METASTASES

Abstract BACKGROUND Recently, non-invasive characterization of brain tumors on MRI has emerged as a promising field of research. The identification of quantitative imaging biomarkers, also known as radiomics, may complement molecular characterization and thereby improve clinical management of neuro-oncologic patients. In this study we aimed to identify imaging predictors with improved performance over clinical parameters in order to stratify patients with brain metastases into high and low risk groups for overall survival (OS). MATERIAL AND METHODS 422 patients (allocated in a 3:1 ratio to a discovery [n=317] and test [n= 105] set) with first diagnosis of brain metastases from different primary tumors from two neuro-oncologic centers were included. In each patient, eight clinical features (age, gender, KPS, systemic disease status, presence of extracranial metastases, number of cerebral metastases, primary tumor and available individual prognostic molecular status eg HER2, BRAF,⋯) were gathered and a total of 321 radiomic MRI features (including shape, first-order and higher-order features) from cerebral MRI (contrast T1-weighted and apparent diffusion coefficient maps) were extracted. Radiomic and clinical features of patients in the discovery set were subjected to different machine learning models in order to classify patients into low- and high-risk groups for OS. By performing a comprehensive grid search the best machine learning model according to the macro-evaluated score and accuracy was identified and evaluated on the testing set. In addition, a subgroup analysis, based on the primary tumor entity was done and confusion matrices were calculated in order to evaluate final predictions. RESULTS With an extra trees classifier including all clinical and 30 radiomic features, we were able to stratify patients into a high- and low-risk group for OS (test set: macro-evaluated = 0.60, accuracy = 0.67). The best performing model was a gradient boosting model only including clinical features (test set: macro-evaluated = 0.62, accuracy = 0.72), while the radiomic features alone led to the poorest results (test set: macro-evaluated = 0.52, accuracy = 0.63). Interestingly, in the subgroup of melanoma patients, the predictive power of radiomic features outperformed the clinical and the combined (radiomics and clinical) features. With a prediction solely based on radiomic features, 80% and 67% of patients were correctly classified into the low- and the high-risk group for OS, respectively. CONCLUSION In conclusion, we found that in the entire study population of patients with brain metastases radiomic features did not allow for a better prediction of the clinical outcome compared to the clinical parameters alone. However, in the subgroup of melanoma patients the predictive power of radiomic features alone was superior compared to clinical features or all features combined.

Survival in patients with brain metastasis secondary to breast cancer from Saudi Arabia.

e14018 Background: Breast cancer (BC) is the most common malignancy in women from Saudi Arabia. Nearly one-third of the patients present with metastatic disease. Data on the incidence, pattern and outcome of brain metastasis (BM) in breast cancer patients is yet to be reported to inform the practice and help in assessing the current standard of care. Methods: A retrospective cohort study between the years 2015 and 2020 that included BC patients with BM was conducted. Demographic data, tumor clinico-pathological features, treatment modalities and outcomes were obtained. Survival, factors influencing survival time and the risk of death were examined. A p-value of less than 0.05 was considered statistically significant. Results: 111 patients with BM due to BC were included in the analysis. All are female with a mean age 50.28 ± 11.61 years. IDC histology (93%), grade III (71%), tumor &gt; T2 (64%) and N-positive (60%) BC accounted for the majority. Human epidermal growth factor receptor2 (HER2)-positive/Hormone receptors (HR)-negative was 21%, HER2-positive/HR-positive was 16%, HR-positive/HER2-negative was 31%, TNBC was 22.5% and unknown subtype in 10%. 60% had metastatic disease on presentation with 41% had both skeletal and visceral metastases. Brain lesions &gt; three were reported in nearly half of the cohort. Whole brain radiotherapy (WBRT), surgical resection and SRS were reported in 84%, 16% and 22%, respectively. The mean survival time was 3.31 years with a maximum of 4.23 years and a minimum of 2.39 years. Patients with HR-positive and HER2-positive BC had a significant longer survival (p=0.039, 0.033 respectively). Neither tumor size nor nodal status in BC patients with BM influenced survival time. The presence of visceral metastasesincreased the likelihood of death in BC patients with BM up to 6 folds (p=0.031). The relationship between risk of death, treatment modalities, and response of BM is shown. Conclusions: Although BM secondary to BC represents a therapeutic challenge with an expected unfavorable impact on survival, mortality was associated with the presence of extra-cranial metastases, particularly visceral metastases in this cohort. Longer survival was seen with specific subtypes (HR-positive and HER2-positive), suggesting advancement in systemic treatments against them. [Table: see text]

First- versus Third-Generation EGFR Tyrosine Kinase Inhibitors in EGFR-Mutated Non-Small Cell Lung Cancer Patients with Brain Metastases

Introduction: Up to 50% of non-small cell lung cancer (NSCLC) harbor EGFR alterations, the most common etiology behind brain metastases (BMs). First-generation EGFR-directed tyrosine kinase inhibitors (EGFR-TKI) are limited by blood-brain barrier penetration and T790M tumor mutations, wherein third-generation EGFR-TKIs, like Osimertinib, have shown greater activity. However, their efficacy has not been well-studied in later therapy lines in NSCLC patients with BMs (NSCLC-BM). We sought to compare outcomes of NSCLC-BM treated with either first- or third-generation EGFR-TKIs in first-line and 2nd-to-5th-line settings. Methods: A retrospective review of NSCLC-BM patients diagnosed during 2010-2019 at Cleveland Clinic, Ohio, US, a quaternary-care center, was performed and reported following 'strengthening the reporting of observational studies in epidemiology' (STROBE) guidelines. Data regarding socio-demographic, histopathological, molecular characteristics, and clinical outcomes were collected. Primary outcomes were median overall survival (mOS) and progression-free survival (mPFS). Multivariable Cox proportional hazards modeling and propensity score matching were utilized to adjust for confounders. Results: 239 NSCLC-BM patients with EGFR alterations were identified, of which 107 received EGFR-TKIs after diagnosis of BMs. 77.6% (83/107) received it as first-line treatment, and 30.8% (33/107) received it in later (2nd-5th) lines of therapy, with nine patients receiving it in both settings. 64 of 107 patients received first-generation (erlotinib/gefitinib) TKIs, with 53 receiving them in the first line setting and 13 receiving it in the 2nd-5th lines of therapy. 50 patients received Osimertinib as third-generation EGFR-TKI, 30 in first-line, and 20 in the 2nd-5th lines of therapy. Univariable analysis in first-line therapy demonstrated mOS of first- and third-generation EGFR-TKIs as 18.2 and 19.4 months, respectively (p = 0.57), while unadjusted mPFS of first- and third-generation EGFR-TKIs was 9.3 and 13.8 months, respectively (p = 0.14). In 2nd-5th line therapy, for first- and third-generation EGFR-TKIs, mOS was 17.3 and 11.9 months, (p = 0.19), while mPFS was 10.4 and 6.08 months, respectively (p = 0.41). After adjusting for age, performance status, presence of extracranial metastases, whole-brain radiotherapy, and presence of leptomeningeal metastases, hazard ratio (HR) for OS was 1.25 (95% CI 0.63-2.49, p = 0.52) for first-line therapy. Adjusted HR for mOS in 2nd-to-5th line therapy was 1.60 (95% CI 0.55-4.69, p = 0.39). Conclusions: No difference in survival was detected between first- and third-generation EGFR-TKIs in either first or 2nd-to-5th lines of therapy. Larger prospective studies are warranted reporting intracranial lesion size, EGFR alteration and expression levels in primary tumor and brain metastases, and response rates.

Predictors of Survival After Stereotactic Radiosurgery for Untreated Single Non-Small Cell Lung Cancer Brain Metastases: 5- and 10-year Results.

Stereotactic radiosurgery (SRS) presents as a good treatment option for smaller, deep-seated brain metastases (BMs). This study aims to determine predictors of SRS failure for patients with non-small cell lung cancer BMs. This was a retrospective study of single non-small cell lung cancer BMs treated using SRS. We included patients >18years with a single, previously untreated lesion. Primary outcome was treatment failure, defined as BMs dimension increase above the initial values. Demographic, clinical, and radiological data were collected to study potential predictors of treatment failure. Worse rates of progression-free survival (PFS) were associated with heterogeneous contrast enhancement (18.1±4.1 vs. 41.9±4months; P < 0.001). Better rates of PFS were associated with volumes <1.06cm3 (log-rank; P= 0.001). Graded prognostic assessment was significantly associated with survival at 120months (log-rank; P < 0.001). Karnofsky Performance Scale was evaluated in 3 strata: 90-100, 80, and ≤70. Mean survival rates for these strata were 31.8±3.9, 10.6±2.2, and 9.8±2.3months, respectively (log-rank; P < 0.001). There were no differences regarding presence of extracranial metastases, age, or lesion location. A multivariable logistic regression found that volume <1.06cm3 was associated with higher survival rates at 10 years (odds ratio: 3.2, 95% confidence interval: 1.3-8.0). Contrast-homogeneous metastases and lesions <1.06cm3 are associated with better rates of PFS. Karnofsky Performance Scale and graded prognostic assessment were associated with more favorable survival rates after 10years. Volume <1.06cm3 was the only significant predictor of survival in the multivariable analysis.

Central nervous system metastasis in gynecologic cancers: Seeking the prognostic factors.

Central nervous system (CNS) metastasis originating from gynecological cancer is a very rare and late manifestation of the disease. Therefore, there is still limited data on prognostic factors for survival. The objective of the present study is to identify prognostic factors for survival in patients with CNS metastasis originating from gynecological cancer. The present retrospective study analyzed the patients with gynecological cancers who were treated due to CNS metastases between January 1999 and December 2019 at Istanbul University Hospital. Forty-seven patients with CNS metastasis of gynecological origin were included in the study. The median age at the time of CNS metastasis was 59 (range 34-93). The median time from initial cancer diagnosis to CNS metastasis was 24.9 (range: 0-108.2) months. Most patients had epithelial ovarian cancer (EOC) (76.6%), followed by endometrial cancer (EC) (14.8%), cervical cancer (CC) (4.3%), and vulvar cancer (VC) (4.3%). By multivariate analysis, the presence of extracranial metastasis (HR: 5.10; 95% CI: 1.71-15.18), Eastern Cooperative Oncology Group (ECOG) performance status ≥3 (HR: 2.92; 95% CI: 1.36-6.26), palliative care only for the treatment of CNS metastasis (HR: 1.47; 95% CI: 0.58-4.11), and treatment-free interval (TFI) <6 months (HR: 2.74; 95% CI: 1.23-6.08) were independent factors that associated with worse survival. Patients with CNS metastasis who have favorable prognostic factors are considered to be appropriate candidates for aggressive and long-term treatment strategies. Extracranial metastasis, ECOG performance status, treatment history of CNS metastasis, and TFI were determined as independent prognostic factors that improved survival. TFI might be taken into account as a prognostic factor for patients with CNS metastasis in gynecological cancer.

Natural history of lung squamous cell brain metastases in patients treated with radiosurgery: a thirty-year experience at a tertiary medical center.

In this study we report our 30-year experience in stereotactic radiosurgery (SRS) treatment of lung squamous cell carcinoma (LUSC) brain metastases (BMs). It will serve to provide detailed longitudinal outcomes and predictors of efficacy in treating LUSC-BMs with SRS. We retrospectively reviewed 51 patients and 109 tumors treated with SRS at our center between 1993 and 2022. Patient demographics, PDL1 genotype, immunotherapy use and mortality cause were recorded. Radiological and clinical outcomes were followed at 1-3-month intervals post-SRS. Cox-regression analysis and Kaplan-Meier survival curves were performed in statistical analysis. We included 37 male and 14 female patients (median age 62.7 years at BM diagnosis). Median overall survival (OS) time was 6.9 months, 6-month OS rate was 62.1%, and Karnofsky performance scale (KPS) was the only independent predictor. Median time for local control maintenance was 7.6 months, 6-month local control rate was 69.1%, with TKI as the only independent predictor. Median time to distant failure was 5.13 months, 6-month distant failure rate was 51.1%, and factors with significant impact included gender (p = 0.002), presence of extracranial metastases (p < 0.001), use of immunotherapy(p < 0.001), PDL1 genotype (p = 0.034), and total intracranial metastases number (p = 0.008). However, no definitive benefits of immunotherapy were identified in patients with higher PDL1 mutational tumors. In this study we defined the natural history of disease progression and outcomes in SRS-treated LUSC-BM patients. We also identified predictors of OS and tumor control among these patients. The findings of this study will serve as a guide when counseling these patients for SRS.

TMIC-03. TUMOR INFILTRATING LYMPHOCYTES IN BRAIN METASTASIS: CLINICOPATHOLOGICAL EVALUATION AND COMPARISON WITH PAIRED PRIMARY

Abstract INTRODUCTION Little is known about tumour-infiltrating lymphocytes (TILs) in brain metastasis (BM) and their utility as predictive biomarker for immunotherapy. AIM: To analyze TILs in BM, and correlate with corresponding paired primary (PP). METHODS Inclusion: Histologically confirmed BM and PP (2015-2020). Exclusion: Hematological malignancies, spinal cord/meningeal metastasis, pediatric age, slides/blocks not available. Final Nf 277 BM; 64 PP. One H&amp;E slide from both PP &amp;BM assessed for stromal TILs (sTILs) and intratumoral TILs (iTILs) as per International TIL Working Group guidelines. RESULTS Median sTILs (10%) were significantly higher than iTILs (1%) in primary and BM (p-value &amp;lt; 0.001). sTILs were mild (&amp;lt;10%) in majority of primary (57.8%) and BM (59.9%), while iTILs were nearly always mild (primary 97.1%; BM 96.9%). Between PP and BM, no change in sTIL category in 48.43%, while conversion in 51.56%, with higher to lower conversion (66.67%) &amp;gt; lower to higher (33.33%). Conversion rate higher for breast (54.3%) &amp;GIT (62.5%) than lung (45.5%) &amp;GUT (40%). In BM, preoperative steroid therapy (PST) showed lower sTILs (≤10%) (p-value= 0.041), and adenocarcinoma histology higher sTILs ( &amp;gt;10%) (p-value= 0.001), while precocious metastasis (p-value= 0.051) and absence of extracranial metastasis (p-value= 0.083) trended towards higher sTILs. Median survival of whole cohort was 20 months (95% CI 14.4-25.68 months). Presence of extracranial metastasis (p-value= 0.01); precocious BM (p-value= 0.007) showed lower overall survival (OS), while adenocarcinoma histology better OS (p-value= 0.029), in both univariate and multivariate analysis. Absence of PST showed longer median survival, though not significant (24.1 vs 19.8months; p-value= 0.19). CONCLUSIONS sTILs predominantly show high &amp;gt;low conversion between PP and BM, signifying lowered immune response in BM. Thus, evaluation of sTILs in BM, wherever tissue available, may be indicated if immunotherapy is considered. Parameters with higher sTILs showed longer survival, possibly indicating prognostic role of tumor microenvironment in BM.

Prognosis after Whole-Brain Radiotherapy for Leptomeningeal Metastasis in Patients with Lung Adenocarcinoma with or without EGFR/ALK Alterations

<h3>Purpose/Objective(s)</h3> Whole-brain radiotherapy (WBRT) is a treatment option for patients with leptomeningeal metastasis (LM) from lung adenocarcinoma. However, there is no consensus on the indication of WBRT, mainly due to a lack of selection criteria for patients who will benefit from WBRT. In addition, the factors associated with better clinical outcomes after WBRT have not been well elucidated. In particular, the impact of <i>EGFR</i> mutations or <i>ALK</i> rearrangement on survival in patients receiving WBRT for LM remains unclear. Here, we conducted a retrospective study to evaluate the prognosis of patients receiving WBRT for LM. <h3>Materials/Methods</h3> We retrospectively evaluated a total of 72 patients who received WBRT for LM from lung adenocarcinoma at our institution between June 2013 and August 2020. Seventy-one patients (98.6%) were diagnosed as LM by radiographic findings without cerebrospinal fluid cytology. Overall survival (OS) was calculated in all 72 patients from the starting date of WBRT until death. The following variables were analyzed as the factors associated with OS: Eastern Cooperative Oncology Group performance status (PS), age, <i>EGFR/ALK</i> status, the number of brain metastases, presence of extracranial metastasis, and primary tumor control. <h3>Results</h3> Among the 72 patients examined, <i>EGFR</i> mutations were found in 40, <i>ALK</i> rearrangement was found in 6, co-alterations were found in 1, and 25 patients had a wild-type for <i>EGFR</i> and <i>ALK</i> alterations. The median follow-up time was 5.2 months (range, 0.5–49.3), 54 of 72 patients (75.0%) died of disease progression, and the median OS was 6.2 months (95% CI; 4.4–12.5). Multivariate analysis indicated that PS 0–1 (<i>P</i> < 0.001), controlled primary tumor (<i>P</i> = 0.011) were independent positive predictors of OS after WBRT. <i>EGFR</i> mutation or <i>ALK</i> rearrangement was not an independent predictor of OS after WBRT (<i>P</i> = 0.10). Of the 47 patients with <i>EGFR</i>-mutant or <i>ALK</i>-rearranged lung adenocarcinoma, 10 received central nervous system–penetrant TKIs against LM before WBRT (the median time from LM diagnosis to WBRT was 2.7 months [range, 1.4–37.2]). No significant survival difference was observed between those with and without prior TKI use (median OS 8.1 vs. 12.5 months, respectively). <h3>Conclusion</h3> Good PS and controlled primary tumor had a significant positive impact on OS after WBRT for LM. <i>EGFR</i> or <i>ALK</i> status did not influence OS.

Impact of Hormone Receptor Status on Development of Brain Metastases from HER2+ Breast Cancer

<h3>Purpose/Objective(s)</h3> Patients with HER2+ breast cancer (BC) are at high risk of developing and dying from brain metastases (BM) compared to patients who have HER2- disease. Some studies have suggested hormone receptor (HR) positivity can delay the development of BM possibly due to endocrine therapies controlling extracranial disease. However, the impact of HR positivity on the time to development of BM in HER2+ disease is not well understood. <h3>Materials/Methods</h3> We retrospectively reviewed data on patients with BM from BC from a single academic institution from 2005–2020, during which time trastuzumab was included in the standard of care. Patients with HER2+ BC and BM were stratified into groups based on HR status, i.e., ER+ and/or PR+. Overall survival (OS) data was analyzed using the Kaplan-Meier method with differences compared by the log-rank test. HR status and time to development of BM were compared using a two-tailed Student's t-test. <h3>Results</h3> Of 363 BC patients with BM, 67 patients (18.5%) were identified as HER2+ (median age 48; range 26–80). 63 (94%) of the 67 patients received trastuzumab. 39 (58.2%) of the 67 patients had HR+ disease (ER+ and/or PR+ disease) and 28 (41.8%) had HR- disease. 30 (76.9%) of 39 patients with HR+ disease received endocrine therapy. In HR+ patients, the median time to the diagnosis of BM was 48.4 mos (SD=57.9 mos), while in patients with HR- disease the median time to the diagnosis of BM was shorter at 29.0 mos (SD=49.1 mos) (p<0.02). The median OS after initial diagnosis of BM for patients with HR+ disease was 27.6 mos, and 9.8 mos for patients with HR- disease (p<0.46). Of the 67 patients, 20 (29.9%) patients presented with one BM, 23 (34.3%) with 2–9 BM, 17 (25.4%) patients with ≥10 BM, and 7 (10.4%) with unknown number of BM. The median number of BM in HR+ patients was 2.0 (SD=2.8), and the median number of BM in HR- patients was 1.0 (SD=3.2) (p<0.43). The median diameter of the dominant BM in HR+ patients was 2.5 cm (SD=1.4 cm; range=0.05–5.4 cm), and the median diameter of the dominant BM in HR- patients was 2.1 cm (SD=1.2 cm; range=0.2–4.4 cm) (p<0.14). Brain imaging was obtained for neurological symptoms in 45 (67.2%) patients; 5 (7.5%) were asymptomatic; and 17 (22.4%) had unknown indication for imaging. 30 patients (44.8%) had extracranial metastases at the initial time of HER2+ BC diagnosis, and their median time to the development of BM was 26.4 mos (SD=25.2 mos). In contrast, 34 patients (50.7%) had no extracranial or BM at BC diagnosis and had longer median interval time to BM development at 53.8 mos (SD=67.5 mos) (p<0.002). <h3>Conclusion</h3> The majority of patients with HER2+ BM were symptomatic at time of BM diagnosis. The most salient factors associated with a decreased time interval to development of BM included HR- status and presence of extracranial metastases at the time of initial HER2+ BC diagnosis.

Therapeutic Options for Brain Metastases in Gynecologic Cancers.

Brain metastases (BM) are rare in gynecologic cancers. Overall BM confers a poor prognosis but other factors such as number of brain lesions, patient age, the presence of extracranial metastasis, the Karnofsky Performance Status (KPS) score, and the type of primary cancer also impact prognosis. Taking a patient's whole picture into perspective is crucial in deciding the appropriate management strategy. The management of BM requires an interdisciplinary approach that frequently includes oncology, neurosurgery, radiation oncology and palliative care. Treatment includes both direct targeted therapies to the lesion(s) as well as management of the neurologic side effects caused by mass effect. There is limited evidence of when screening for BM in the gynecology oncology patient is warranted but it is recommended that any cancer patient with new focal neurologic deficit or increasing headaches should be evaluated. The primary imaging modality for detection of BM is MRI, but other imaging modalities such as CT and PET scan can be used for certain scenarios. New advances in radiation techniques, improved imaging modalities, and systemic therapies are helping to discover BM earlier and provide treatments with less detrimental side effects.

Influence of temporal muscle thickness on the outcome of radiosurgically treated patients with brain metastases from non-small cell lung cancer.

The purpose of this study was to assess the impact of temporal muscle thickness (TMT), a surrogate marker for sarcopenia, in radiosurgically treated patients with brain metastases (BMs) from non-small cell lung cancer (NSCLC). For 566 patients with BMs from NSCLC in the period between June 2012 and December 2019, TMT values were retrospectively measured on the planning brain magnetic resonance imaging (MRI) studies that had been obtained before their first Gamma Knife radiosurgery treatment (GKRS1). Predefined sex-specific TMT cutoff values were used to stratify the study cohort into patients at risk for sarcopenia and patients with normal muscle status. Cox regression models adjusted for other prognostic parameters were used to evaluate sarcopenia as an independent prognostic factor. In sarcopenia patients with a TMT below the sex-specific cutoff values, the risk of death was significantly increased (HR 1.908, 95% CI 1.550-2.349, p < 0.001). In addition, sarcopenia was revealed as an independent prognostic factor even after adjusting for age groups, sex, number of BMs, presence of extracranial metastases, NSCLC subtypes, Karnofsky Performance Status groups, recursive partitioning analysis classes, and concomitant immunotherapy or targeted therapy (HR 1.680, 95% CI 1.347-2.095, p < 0.001). However, patients at risk for sarcopenia showed no significant differences in the estimated mean time until local BM progression after GKRS1, compared to patients with normal muscle status (p = 0.639). TMT obtained from planning MRI studies is an independent prognostic marker in radiosurgically treated patients with BMs from NSCLC and may aid patient stratification in future clinical trials.

External Validation of the Graded Prognostic Assessment in Patients with Brain Metastases from Small Cell Lung Cancer.

Background: Recently, graded prognostic assessment (GPA) for small cell lung cancer (SCLC) patients with brain metastases has been developed. This includes age, performance status, number of brain metastases and presence of extracranial metastases. The aim of the present study was to validate this four-tiered prognostic score in a European cohort of patients. Methods: The retrospective validation study included 180 patients from two centers in Germany and Norway. Results: Median survival from radiological diagnosis of brain metastases was 7 months. The GPA point sum as continuous variable (0–4 points) was significantly associated with survival (p < 0.001). However, no significant survival difference was observed between patients in the two strata with better survival (3.5–4 and 2.5–3 points, respectively). Long-term survival in the poor prognosis group (0–1 points) was better than expected. Conclusion: This study supports the prognostic impact of all four parameters contributing to the GPA. The original way of grouping the parameters and breaking the final strata did not give optimal results in this cohort. Therefore, additional validation databases from different countries should be created and evaluated.

Programmed cell death 1 pathway inhibitors improve the overall survival of small cell lung cancer patients with brain metastases

PurposeThe objective of this study was to evaluate the safety and efficacy of immune checkpoint inhibitors in small cell lung cancer patients with brain metastases.MethodsWe retrospectively reviewed the records of small cell lung cancer patients with brain metastases treated with chemotherapy and radiotherapy for brain metastases with or without immune checkpoint inhibitors at our institution from January 2019 to January 2021. Patients were divided into two groups. In Group A, patients received chemotherapy and radiotherapy for brain metastases. In Group B, patients received chemotherapy, radiotherapy for brain metastases and at least four cycles of immunotherapy. Overall survival and intracranial progression-free survival were assessed using Kaplan–Meier estimates and Cox regression models.ResultsA total of 282 patients were enrolled in our study. At the end of the study (May 12, 2021), the median overall survival was 13.3 months among 218 patients in Group A and 33.4 months among 64 patients in Group B (hazards ratio [HR] 0.320, 95% confidence interval [CI], 0.189–0.545, P < 0.001). Both univariate and multivariate analyses suggested that two factors were significantly correlated with overall survival: the inclusion of immunotherapy in the regimen and the presence of extracranial metastases. The median intracranial progression-free survival was 6.93 months in Group A and 10.73 months in Group B (HR = 0.540, 95% CI, 0.346–0.841, P = 0.006). The intracranial objective response rate of Group B was greater than that of Group A, but the intracranial disease control rate was similar between the groups.ConclusionImmunotherapy plus chemotherapy and radiotherapy for brain metastases showed promising efficacy for small cell lung cancer patients with brain metastases.