Prophylactic Cranial Irradiation in Limited-Stage Small Cell Lung Cancer: A Meta-Analysis.

The role of prophylactic cranial irradiation (PCI) in limited-stage small cell lung cancer (LS-SCLC) has been questioned in the era of magnetic resonance imaging (MRI). The purpose of this study was to re-evaluate the efficacy of PCI in patients with LS-SCLC. Three electronic databases were searched, including PubMed, Embase, and the Cochrane Library from January 2012 to April 2022. All relevant publications were included based on the inclusion criteria, and survival data and brain metastasis (BM) rates were extracted and pooled. Ten studies were selected which involved 532 patients who received PCI and 613 patients who did not receive PCI. In pooled estimates, PCI significantly improved overall survival (OS) and progression-free survival (PFS) [hazard ratio (HR) = 0.71, 95% confidence interval (CI): 0.61-0.82, p <0.001; HR = 0.68, 95% CI: 0.48-0.97, p = 0.03, respectively]. Additionally, the use of PCI was associated with a significant reduction in the risk of brain metastasis (BM, risk ratio = 0.64, 95% CI: 0.46-0.90, p = 0.009). In subgroup analyses. The authors found that the PCI effects on OS were independent of region and the use of brain imaging after initial treatment. These findings demonstrate that PCI improves OS and PFS while decreasing the risk of BM in patients with LS-SCLC, implying that PCI remains necessary even in the MRI era. Key Words: Prophylactic cranial irradiation, Small cell lung cancer, Magnetic resonance imaging, Brain metastasis.

Outcomes of the patients with metastatic male breast cancer.

BACKGROUND: The goal of this research is to investigate the clinical characteristics and prognosis of men with metastatic breast cancer (mMBC). METHODS: A retrospective analysis of the data of 28 patients was conducted. Kaplan-Meier and Cox regression analyses were used to assess overall survival (OS) and prognostic variables. RESULTS: At the time of diagnosis, the median age was 57 years (range 26-86). The most prevalent pathological subtype was invasive ductal carcinoma (92.6%). HER2 positivity was 21.6% in patients, with estrogen and progesterone receptor positivity at 96.4% and 71.4%, respectively. Bone-75%, lung-39.3%, brain-21.4%, and adrenal gland-10.7% were the most prevalent metastatic sites. Trastuzumab-based chemotherapy was given to six patients. During the study period, 14 patients (or half) died. All patients had a median OS of 42.6 months (range: 21.6-63.7). The OS rates after 1, 3, and 5 years were 95.7%, 54.2%, and 36.6%, respectively. The number of metastatic locations (P = 0.045), brain metastasis (P = 0.033), and a history of regular alcohol intake (P = 0.008) were all shown to be statistically significant factors affecting OS in univariate analysis. However, multivariate analysis did not support the findings. In addition, we discovered that trastuzumab-based therapy and de-novo metastatic disease had no effect on OS for mMBC. CONCLUSIONS: The data on mMBC is restricted because of its rarity. The prognosis of mMBC was shown to be poor in this investigation. Despite the small number of patients, we discovered that in univariate analysis, having brain metastases, the number of metastatic locations, and a history of alcohol intake may be prognostic factors.

Human Epidermal Growth Factor Receptor 2-Low Breast Cancer Brain Metastases: An Opportunity for Targeted Systemic Therapies in a High-Need Patient Population.

PURPOSE: Trastuzumab deruxtecan is a new treatment option for patients with advanced human epidermal growth factor receptor 2 (HER2)-low breast cancer (BC). Although HER2-low status has been characterized in early and advanced BC, it has yet to be fully characterized in brain metastases (BrM). METHODS: Patients who underwent surgery for BC BrM at Sunnybrook Health Sciences Centre and for whom HER2 status was available on resected BrM were studied. Estrogen receptor, progesterone receptor, and HER2 status were assessed on the basis of ASCO/College of American Pathologists (CAP) guidelines. HER2-zero was defined as immunohistochemistry (IHC) 0; HER2-low was defined as IHC 1+ or IHC 2+ with fluorescence in situ hybridization (FISH)-negative status. HER2-positive (HER2+) was defined as IHC 3+ or IHC 2+ with positive FISH. Clinicopathologic features were recorded. We also assessed the prognostic association between extent of HER2 expression and (1) brain-specific progression-free survival (bsPFS), as well as (2) overall survival (OS). RESULTS: In this retrospective cohort of 102 patients with resected BC BrM, 53% (n = 54) were HER2+, 29.4% (n = 30) were HER2-low, and 17.6% (n = 18) had HER2-zero status. Among BrM that were triple-negative on the basis of ASCO/CAP guidelines, 63.6% (n = 14/22) were reclassified as being HER2-low. Sixty percent (n = 15/25) of BrM that were hormone receptor-positive/HER2-negative (HR+/HER2-) were reclassified as being HER2-low. In total, 51 patients had matched primary breast and BrM tissue available; results of HER2 status when categorized as HER2-zero, HER2-low, and HER2+ were concordant in 82.3% (n = 42/51) of cases (Cohen's kappa, 0.58; P = .07). There was no significant association between HER2-zero, HER2-low, and HER2+ status in BrM and either bsPFS or OS. CONCLUSION: Among patients with surgically resected BrM, a high proportion of those with metastatic triple-negative BC and HR+/HER2- disease have HER2-low BrM with potential to benefit from HER2-targeted therapy.

Pre-operative vs. post-operative stereotactic radiosurgery for operative metastatic brain tumors: study protocol for a phase III clinical trial.

BACKGROUND AND OBJECTIVES: Almost one third of cancer patients in the United States will develop brain metastases on an annual basis. Surgical resection is indicated in the setting of brain metastases for reasons, such as maximizing local control in select patients, decompression of mass effect, and/or tissue diagnosis. The current standard of care following resection of a brain metastasis has shifted from whole brain radiation therapy to post-operative stereotactic radiosurgery (SRS). However, there is a significant rate of local recurrence within one year of postoperative SRS. Emerging retrospective and prospective data suggest pre-operative SRS is a safe and potentially effective treatment paradigm for surgical brain metastases. This trial intends to determine, for patients with an indication for resection of a brain metastasis, whether there is an increase in the time to a composite endpoint of adverse outcomes; including the first occurrence of either: local recurrence, leptomeningeal disease, or symptomatic radiation brain necrosis - in patients who receive pre-operative SRS as compared to patients who receive post-operative SRS. METHODS: This randomized phase III clinical trial compares pre-operative with post-operative SRS for brain metastases. A dynamic random allocation procedure will allocate an equal number of patients to each arm: pre-operative SRS followed by surgery or surgery followed by post-operative SRS. EXPECTED OUTCOMES: If pre-operative SRS improves outcomes relative to post-operative SRS, this will establish pre-operative SRS as superior. If post-operative SRS proves superior to pre-operative SRS, it will remain a standard of care and halt the increasing utilization of pre-operative SRS. If there is no difference in pre- versus post-operative SRS, then pre-operative SRS may still be preferred, given patient convenience and the potential for a condensed timeline. DISCUSSION: Emerging retrospective and prospective data have demonstrated some benefits of pre-op SRS vs. post-op SRS. This study will show whether there is an increase in the time to the composite endpoint. Additionally, the study will compare overall survival; patient-reported outcomes; morbidity; completion of planned therapies; time to systemic therapy; time to regional progression; time to CNS progression; time to subsequent treatment; rate of radiation necrosis; rate of local recurrence; and rate of leptomeningeal disease. TRIAL REGISTRATION NUMBER: NCT03750227 (Registration date: 21/11/2018).

Deep learning-based metastasis detection in patients with lung cancer to enhance reproducibility and reduce workload in brain metastasis screening with MRI: a multi-center study.

OBJECTIVES: To assess whether a deep learning-based system (DLS) with black-blood imaging for brain metastasis (BM) improves the diagnostic workflow in a multi-center setting. MATERIALS AND METHODS: In this retrospective study, a DLS was developed in 101 patients and validated on 264 consecutive patients (with lung cancer) having newly developed BM from two tertiary university hospitals, which performed black-blood imaging between January 2020 and April 2021. Four neuroradiologists independently evaluated BM either with segmented masks and BM counts provided (with DLS) or not provided (without DLS) on a clinical trial imaging management system (CTIMS). To assess reading reproducibility, BM count agreement between the readers and the reference standard were calculated using limits of agreement (LoA). Readers' workload was assessed with reading time, which was automatically measured on CTIMS, and were compared between with and without DLS using linear mixed models considering the imaging center. RESULTS: In the validation cohort, the detection sensitivity and positive predictive value of the DLS were 90.2% (95% confidence interval [CI]: 88.1-92.2) and 88.2% (95% CI: 85.7-90.4), respectively. The difference between the readers and the reference counts was larger without DLS (LoA: -0.281, 95% CI: -2.888, 2.325) than with DLS (LoA: -0.163, 95% CI: -2.692, 2.367). The reading time was reduced from mean 66.9 s (interquartile range: 43.2-90.6) to 57.3 s (interquartile range: 33.6-81.0) (P <.001) in the with DLS group, regardless of the imaging center. CONCLUSION: Deep learning-based BM detection and counting with black-blood imaging improved reproducibility and reduced reading time, on multi-center validation.

The relationship between brain metastasis and HER2 expression status in gastric cancer

Background Brain metastasis (BM) in gastric cancer (GC) is underestimated, and human epidermal growth factor receptor 2 (HER2) overexpression is a durable poor prognostic factor. We explored the relationship between the two and made a survival analysis. Methods HER2 expression and BM status were collected from GC patients who were diagnosed between December 2009 and May 2021. We collected GC patients diagnosed between 2010 and 2016 from the SEER database. The primary endpoint was survival from the diagnosis of BM. Multivariable logistic regression was used to determine potential risk factors of BM at diagnosis in SEER database. Survival analysis was performed using the Kaplan–Meier method. Result There were 513 HER2-positive GC patients, including 16 (3.1%) with BM. Among 38 brain metastasis GC patients we collected, 16 (42.1%) patients were HER2 positive. We collected 34,199 GC patients from the SEER database and there were 260 (0.76%) patients with BM at diagnosis. GC patients that are male, white, of younger age, with primary lesions located in the proximal stomach or with distant lymph nodes, liver, bone, or lung metastasis are more likely to develop BM. The median overall survival time from diagnosis of BM was 12.73 months, and the survival time from brain metastasis of HER2-positive patients was numerically shorter, though the difference was not significant (5.30 months vs.16.13 months, P = 0.28.) Conclusion The incidence of BM in patients with HER2-positive gastric cancer is 4.08 times higher than that in general patients. The median overall survival time from BM is shorter for HER2-positive patients (AU)

Comprehensive genomic profiling to identify actionable alterations for breast cancer brain metastases in the Chinese population.

BACKGROUND: Breast cancer brain metastasis (BCBM) is a crucial issue in the treatment of breast cancer and is associated with poor prognosis. Therefore, novel therapeutic targets are urgently needed in clinical practice. In this study, we aimed to identify potential actionable targets in brain metastases (BMs) utilising the FoundationOne® CDx (F1CDx). PATIENTS AND METHODS: Formalin-fixed paraffin-embedded archived specimens including 16 primary breast tumours (PTs), 49 BCBMs and 7 extracranial metastases (ECMs) from 54 patients who underwent surgery for BCBM were tested using F1CDx. Tumour-infiltrated lymphocytes (TILs) of BMs were also tested using haematoxylin-eosin staining. RESULTS: The median tumour mutational burden (TMB) and TILs in BMs were 5.0 (range 0-29) mut/Mb and 1.0% (range 0%-5.0%), respectively. High TMB (≥10 mut/Mb) was detected in four cases (8%). Genomic alterations (GAs) were detected in all samples. The top-ranked somatic mutations in BMs were TP53 (82%), PIK3CA (35%), MLL2 (22%), BRCA2 (14%) and ATM (14%) and the most prevalent copy number alterations were ERBB2 (64%), RAD21 (36%), CCND1 (32%), FGF19 (30%) and FGF3 (30%). The most prevalent GAs were relatively consistent between paired PTs and BMs. Actionable GAs were detected in 94% of all BMs. Consistent rate in actionable GAs was 38% (6/16) between paired PTs/ECMs and BMs. Compared to matched PTs/ECMs, additional actionable GAs (BRAF, FGFR1, PTEN, KIT and CCND1) were discovered in 31% (5/16) of the BMs. CONCLUSIONS: TMB and TILs were relatively low in BCBMs. Comparable consistency in actionable GAs was identified between BCBMs and matched PTs/ECMs. It was, therefore, logical to carry out genomic testing for BCBMs to identify potential new therapeutic targets when BCBM specimens were available, as ∼31% of samples carried additional actionable GAs.

Clinical features and prognostic factors of nasopharyngeal carcinoma with brain metastases.

BACKGROUND: Brain metastasis in nasopharyngeal carcinoma is a rare occurrence, and the characteristics of patients in this subgroup remain poorly defined. This study aims to delineate the clinical features, treatment modalities, prognostic factors, and survival of nasopharyngeal carcinoma patients with brain metastasis. METHODOLOGY: A retrospective analysis was conducted on patients diagnosed with nasopharyngeal carcinoma who developed brain metastasis and were treated at the Sun Yat-sen University Cancer Center between July 2000 and July 2023. Clinical data from patients were collected and used to assess their survival after brain metastases and prognostic factors. RESULTS: Among 82,434 nasopharyngeal carcinoma patients, 40 (0.06 %) developed Brain metastasis with a median follow-up of 5.1 years. The predominant histological subtype was non-keratinizing squamous cell carcinoma (85 %). The median post-BM survival was 25 months. The age, the Eastern Cooperative Oncology Group (ECOG), and the procedural treatment of BM were prognostic factors. Notably, patients receiving local treatments had significantly prolonged post-BM survival compared to those receiving systemic therapy alone (median, 47.00 vs. 11.00 months; p = 0.011). CONCLUSIONS: This is the largest cohort of brain metastasis in nasopharyngeal carcinoma to date. Local therapeutic measures after brain metastasis can significantly enhance the prognosis of these patients, particularly when radiotherapy is applied.

Factors associated with overall survival in breast cancer patients with leptomeningeal disease (LMD): a single institutional retrospective review.

BACKGROUND: Breast cancer-related leptomeningeal disease (BC-LMD) is a dire diagnosis for 5-8% of patients with breast cancer (BC). We conducted a retrospective review of BC-LMD patients diagnosed at Moffitt Cancer Center from 2011 to 2020, to determine the changing incidence of BC-LMD, factors which are associated with the progression of BC CNS metastasis to BC-LMD, and factors which are associated with OS for patients with BC-LMD. METHODS: Patients with BC and brain/spinal metastatic disease were identified. For those who eventually developed BC-LMD, we used Kaplan-Meier survival curve, log-rank test, univariable, and multivariate Cox proportional hazards regression model to identify factors affecting time from CNS metastasis to BC-LMD and OS. RESULTS: 128 cases of BC-LMD were identified. The proportion of BC-LMD to total BC patients was higher between 2016 and 2020 when compared to 2011-2015. Patients with HR+ or HER2 + BC experienced longer times between CNS metastasis and LMD than patients with triple-negative breast cancer (TNBC). Systemic therapy and whole-brain radiation therapy (WBRT) was associated with prolonged progression to LMD in all patients. Hormone therapy in patients with HR + BC were associated with a delayed BC-CNS metastasis to LMD progression. Lapatinib treatment was associated with a delayed progression to LMD in patients with HER2 + BC. Patients with TNBC-LMD had shorter OS compared to those with HR + and HER2 + BC-LMD. Systemic therapy, intrathecal (IT) therapy, and WBRT was associated with prolonged survival for all patients. Lapatinib and trastuzumab therapy was associated with improved OS in patients with HER2 + BC-LMD. CONCLUSIONS: Increasing rates of BC-LMD provide treatment challenges and opportunities for clinical trials. Prospective trials testing lapatinib and/or similar tyrosine kinase inhibitors, IT therapies, and combination treatments are urgently needed.

DEGRO guideline for personalized radiotherapy of brain metastases and leptomeningeal carcinomatosis in patients with breast cancer.

PURPOSE: The aim of this review was to evaluate the existing evidence for radiotherapy for brain metastases in breast cancer patients and provide recommendations for the use of radiotherapy for brain metastases and leptomeningeal carcinomatosis. MATERIALS AND METHODS: For the current review, a PubMed search was conducted including articles from 01/1985 to 05/2023. The search was performed using the following terms: (brain metastases OR leptomeningeal carcinomatosis) AND (breast cancer OR breast) AND (radiotherapy OR ablative radiotherapy OR radiosurgery OR stereotactic OR radiation). CONCLUSION AND RECOMMENDATIONS: Despite the fact that the biological subtype of breast cancer influences both the occurrence and relapse patterns of breast cancer brain metastases (BCBM), for most scenarios, no specific recommendations regarding radiotherapy can be made based on the existing evidence. For a limited number of BCBM (1-4), stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (SRT) is generally recommended irrespective of molecular subtype and concurrent/planned systemic therapy. In patients with 5-10 oligo-brain metastases, these techniques can also be conditionally recommended. For multiple, especially symptomatic BCBM, whole-brain radiotherapy (WBRT), if possible with hippocampal sparing, is recommended. In cases of multiple asymptomatic BCBM (≥ 5), if SRS/SRT is not feasible or in disseminated brain metastases (> 10), postponing WBRT with early reassessment and reevaluation of local treatment options (8-12 weeks) may be discussed if a HER2/Neu-targeting systemic therapy with significant response rates in the central nervous system (CNS) is being used. In symptomatic leptomeningeal carcinomatosis, local radiotherapy (WBRT or local spinal irradiation) should be performed in addition to systemic therapy. In patients with disseminated leptomeningeal carcinomatosis in good clinical condition and with only limited or stable extra-CNS disease, craniospinal irradiation (CSI) may be considered. Data regarding the toxicity of combining systemic therapies with cranial and spinal radiotherapy are sparse. Therefore, no clear recommendations can be given, and each case should be discussed individually in an interdisciplinary setting.

Intraventricular Cerebral Metastases: A Comprehensive Systematic Review.

BACKGROUND/AIM: Intraventricular cerebral metastases (IVCM) are a rare but clinically significant subset of brain metastases. This systematic review aimed to provide a comprehensive analysis of IVCM by synthesizing current literature on epidemiology, clinical presentation, imaging features, pathophysiology, and treatment options. MATERIALS AND METHODS: A systematic literature search was conducted, identifying 11 relevant studies encompassing 11 studies encompassing 842 IVCM cases. Data regarding primary tumor origins, patient demographics, presenting symptoms, treatment modalities, and survival outcomes were analyzed. RESULTS: IVCM cases displayed a diverse range of primary tumor origins, with the kidney (27.4%), thyroid (21.6%), lung (19.8%), colon (11.7%), melanoma (8.4%), and breast ductal carcinoma (7.9%) being common sources. Patients presented with a wide spectrum of symptoms, including headaches (42.3%), nausea (31.5%), altered mental status (25.7%), neurological deficits (18.2%), and others. Treatment approaches varied, encompassing surgical resection (41.2%), radiation therapy (32.5%), chemotherapy (15.3%), and immunotherapy (7.9%). Overall survival was generally limited, with a mean duration of approximately 10.3 months (±8.7 months). The time to recurrence after treatment exhibited considerable variability. CONCLUSION: IVCM represents a challenging and underexplored metastatic disease. This systematic review underscores the need for further research to enhance our understanding of IVCM's pathophysiology and develop tailored diagnostic and treatment approaches. Such efforts are crucial to improving outcomes and the overall quality of life for patients facing this complex condition. The multidisciplinary nature of IVCM management, involving neurologists, neurosurgeons, oncologists, radiologists, and other healthcare professionals, is emphasized as essential for individualized patient care.

Can we predict overall survival using machine learning algorithms at 3-months for brain metastases from non-small cell lung cancer after gamma knife radiosurgery?

Gamma knife radiosurgery (GRKS) is widely used for patients with brain metastases; however, predictions of overall survival (OS) within 3-months post-GKRS remain imprecise. Specifically, more than 10% of non-small cell lung cancer (NSCLC) patients died within 8 weeks of post-GKRS, indicating potential overtreatment. This study aims to predict OS within 3-months post-GKRS using machine learning algorithms, and to identify prognostic features in NSCLC patients. We selected 120 NSCLC patients who underwent GKRS at Chungbuk National University Hospital. They were randomly assigned to training group (n = 80) and testing group (n = 40) with 14 features considered. We used 3 machine learning (ML) algorithms (Decision tree, Random forest, and Boosted tree classifier) to predict OS within 3-months for NSCLC patients. And we extracted important features and permutation features. Data validation was verified by physician and medical physicist. The accuracy of the ML algorithms for predicting OS within 3-months was 77.5% for the decision tree, 72.5% for the random forest, and 70% for the boosted tree classifier. The important features commonly showed age, receiving chemotherapy, and pretreatment each algorithm. Additionally, the permutation features commonly showed tumor volume (>10 cc) and age as critical factors each algorithm. The decision tree algorithm exhibited the highest accuracy. Analysis of the decision tree visualized data revealed that patients aged (>71 years) with tumor volume (>10 cc) were increased risk of mortality within 3-months. The findings suggest that ML algorithms can effectively predict OS within 3-months and identify crucial features in NSCLC patients. For NSCLC patients with poor prognoses, old age, and large tumor volumes, GKRS may not be a desirable treatment.

Vascular characterization reveals immunomodulatory targets for brain metastases.

Brain metastases are clinically challenging due to the unique brain microenvironment. In this issue of Cancer Cell, Bejarano et al. use transcriptional profiling and data integration to shed light on the molecular and cellular composition of the vasculature in brain metastases, identifying CD276 as an immunomodulatory target for therapy.

Dosimetric evaluation of LINAC-based single-isocenter multi-target multi-fraction stereotactic radiosurgery with more than 20 targets: comparing MME, HyperArc, and RapidArc.

BACKGROUND: To compare the dosimetric quality of three widely used techniques for LINAC-based single-isocenter multi-target multi-fraction stereotactic radiosurgery (fSRS) with more than 20 targets: dynamic conformal arc (DCA) in BrainLAB Multiple Metastases Elements (MME) module and volumetric modulated arc therapy (VMAT) using RapidArc (RA) and HyperArc (HA) in Varian Eclipse. METHODS: Ten patients who received single-isocenter fSRS with 20-37 targets were retrospectively replanned using MME, RA, and HA. Various dosimetric parameters, such as conformity index (CI), Paddick CI, gradient index (GI), normal brain dose exposures, maximum organ-at-risk (OAR) doses, and beam-on times were extracted and compared among the three techniques. Wilcoxon signed-rank test was used for statistical analysis. RESULTS: All plans achieved the prescribed dose coverage goal of at least 95% of the planning target volume (PTV). HA plans showed superior conformity compared to RA and MME plans. MME plans showed superior GI compared to RA and HA plans. RA plans resulted in significantly higher low and intermediate dose exposure to normal brain compared to HA and MME plans, especially for lower doses of ≥ 8Gy and ≥ 5Gy. No significant differences were observed in the maximum dose to OARs among the three techniques. The beam-on time of MME plans was about two times longer than RA and HA plans. CONCLUSIONS: HA plans achieved the best conformity, while MME plans achieved the best dose fall-off for LINAC-based single-isocenter multi-target multi-fraction SRS with more than 20 targets. The choice of the optimal technique should consider the trade-offs between dosimetric quality, beam-on time, and planning effort.

Local hero: A phase II study of local therapy only (stereotactic radiosurgery and / or surgery) for treatment of up to five brain metastases from HER2+ breast cancer. (TROG study 16.02).

Introduction, A decade ago, stereotactic radiosurgery (SRS) without whole brain radiotherapy (WBRT) was emerging as preferred treatment for oligometastatic brain metastases. Studies of cavity SRS after neurosurgery were underway. Data specific to metastatic HER2 breast cancer (MHBC), describing intracranial, systemic and survival outcomes without WBRT, were lacking. A Phase II study was designed to address this gap. Method, Adults with MHBC, performance status 0-2, ≤ five BrM, receiving/planned to receive HER2-targeted therapy were eligible. Exclusions included leptomeningeal disease and prior WBRT. Neurosurgery allowed ≤6 weeks before registration and required for BrM >4 cm. Primary endpoint was 12-month requirement for WBRT. Secondary endpoints; freedom from (FF-) local failure (LF), distant brain failure (DBF), extracranial disease failure (ECDF), overall survival (OS), cause of death, mini-mental state examination (MMSE), adverse events (AE). Results, Twenty-five patients accrued Decembers 2016-2020. The study closed early after slow accrual. Thirty-seven BrM and four cavities received SRS. Four cavities and five BrM were observed. At 12 months: one patient required WBRT (FF-WBRT 95 %, 95 % CI 72-99), FFLF 91 % (95 % CI 69-98), FFDBF 57 % (95 % CI 34-74), FFECDF 64 % (95 % CI 45-84), OS 96 % (95 % CI 74-99). Two grade 3 AE occurred. MMSE was abnormal for 3/24 patients at baseline and 1/17 at 12 months. Conclusion, At 12 months, SRS and/or neurosurgery provided good control with low toxicity. WBRT was not required in 95 % of cases. This small study supports the practice change from WBRT to local therapies for MHBC BrM.

Metastasis infiltrating tumor to meningioma: a case report.

BACKGROUND: There have been many reports of tumor-to-tumor metastasis, in which cancer metastasizes directly into meningiomas. However, metastasis infiltrating tumors in which cancer metastasizes around meningiomas are rare. Therefore, we report a case of metastasis originating from lung cancer that infiltrated meningioma. CASE PRESENTATION: A 79-year-old Japanese woman underwent head magnetic resonance imaging for brain metastasis screening before lung cancer surgery. At that time, asymptomatic meningioma of the left frontal region was accidentally found. Magnetic resonance imaging 6 months later revealed a lesion suspected to be a metastatic brain tumor close to the meningioma. Brain tumor resection was performed, and histopathological diagnosis was meningioma and metastatic brain tumor. Metastatic cancer had invaded the meningioma at the boundary between the brain tumor and metastasis. CONCLUSIONS: A sudden change in imaging findings on routine examination of meningiomas in patients with lung carcinoma may indicate a metastatic brain tumor. The form of cancer metastasis to meningioma is not limited to tumor-to-tumor metastasis, but also includes metastasis infiltrating tumors near the meningioma.

A large open access dataset of brain metastasis 3D segmentations on MRI with clinical and imaging information.

Resection and whole brain radiotherapy (WBRT) are standard treatments for brain metastases (BM) but are associated with cognitive side effects. Stereotactic radiosurgery (SRS) uses a targeted approach with less side effects than WBRT. SRS requires precise identification and delineation of BM. While artificial intelligence (AI) algorithms have been developed for this, their clinical adoption is limited due to poor model performance in the clinical setting. The limitations of algorithms are often due to the quality of datasets used for training the AI network. The purpose of this study was to create a large, heterogenous, annotated BM dataset for training and validation of AI models. We present a BM dataset of 200 patients with pretreatment T1, T1 post-contrast, T2, and FLAIR MR images. The dataset includes contrast-enhancing and necrotic 3D segmentations on T1 post-contrast and peritumoral edema 3D segmentations on FLAIR. Our dataset contains 975 contrast-enhancing lesions, many of which are sub centimeter, along with clinical and imaging information. We used a streamlined approach to database-building through a PACS-integrated segmentation workflow.

A real-world cohort study of first-line afatinib in patients with EGFR-mutant advanced non-small cell lung cancer in Vietnam.

BACKGROUND: This study aimed to evaluate the efficacy and side effects of first-line afatinib treatment in a real-world setting in Vietnam. METHODS: This retrospective study was conducted across nine hospitals in Vietnam. Advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients who received afatinib as first-line therapy between April 2018 and June 2022 were included, and patient medical records were reviewed. Key outcomes were overall response rate (ORR), time-to-treatment failure (TTF), and tolerability. RESULTS: A total of 343 patients on first-line afatinib were eligible for the study. EGFR exon 19 deletion (Del19) alone was detected in 46.9% of patients, L858R mutation alone in 26.3%, and other uncommon EGFR mutations, including compound mutations, in 26.8%. Patients with brain metastases at baseline were 25.4%. Patients who received 40 mg, 30 mg, and 20 mg as starting doses of afatinib were 58.6%, 39.9%, and 1.5%, respectively. The ORR was 78.1% in the overall population, 82.6% in the Del19 mutation subgroup, 73.3% in the L858R mutation subgroup, and 75.0% in the uncommon mutation subgroup (p > 0.05). The univariate and multivariate analyses indicate that the ORR increased when the starting dose was 40 mg compared to starting doses below 40 mg (83.9% vs. 74.3%, p = 0.034). The median TTF (mTTF) was 16.7 months (CI 95%: 14.8-18.5) in all patients, with a median follow-up time of 26.2 months. The mTTF was longer in patients in the common EGFR mutation subgroup (Del19/L858R) than in those in the uncommon mutation subgroup (17.5 vs. 13.8 months, p = 0.045) and in those without versus with brain metastases at baseline (17.5 vs. 15.1 months, p = 0.049). There were no significant differences in the mTTF between subgroups based on the starting dose of 40 mg and < 40 mg (16.7 vs. 16.9 months, p > 0.05). The most common treatment-related adverse events (any grade/grade ≥ 3) were diarrhea (55.4%/3.5%), rash (51.9%/3.2%), paronychia (35.3%/5.0%), and stomatitis (22.2%/1.2%). CONCLUSIONS: Afatinib demonstrated clinical effectiveness and good tolerability in Vietnamese EGFR-mutant NSCLC patients. In our real-world setting, administering a starting dose below 40 mg might result in a reduction in ORR; however, it might not have a significant impact on TTF.

Clinical outcomes of melanoma brain metastases treated with nivolumab and ipilimumab alone versus nivolumab and ipilimumab with stereotactic radiosurgery.

PURPOSE: Upfront dual checkpoint blockade with immune checkpoint inhibitors (ICI) has demonstrated efficacy for treating melanoma brain metastases (MBM) in asymptomatic patients. Whether the combination of stereotactic radiosurgery (SRS) with dual checkpoint blockade improves outcomes over dual-checkpoint blockade alone is unknown. We evaluated clinical outcomes of patients with MBM receiving ICI with nivolumab and ipilimumab, with and without SRS. METHODS: 49 patients with 158 MBM receiving nivolumab and ipilimumab for untreated MBM between 2015 and 2022 were identified at our institution. Patient and tumor characteristics including age, Karnofsky Performance Status (KPS), presence of symptoms, cancer history, MBM burden, and therapy course were recorded. Outcomes measured from initiation of MBM-directed therapy included overall survival (OS), local control (LC), and distant intracranial control (DIC). Time-to-event analysis was conducted with the Kaplan-Meier method. RESULTS: 25 patients with 74 MBM received ICI alone, and 24 patients with 84 MBM received concurrent SRS. Median follow-up was 24 months. No differences in age (p = 0.96), KPS (p = 0.85), presence of symptoms (p = 0.79), prior MBM (p = 0.68), prior MBM-directed surgery (p = 0.96) or SRS (p = 0.68), MBM size (p = 0.67), or MBM number (p = 0.94) were seen. There was a higher rate of nivolumab and ipilimumab course completion in the SRS group (54% vs. 24%; p = 0.029). The SRS group received prior immunotherapy more often than the ICI alone group (54% vs. 8.0%; p < 0.001). There was no significant difference in 1-year OS (72% vs. 71%, p = 0.20) and DIC (63% v 51%, p = 0.26) between groups. The SRS group had higher 1-year LC (92% vs. 64%; p = 0.002). On multivariate analysis, LC was improved with combination therapy (AHR 0.38, p = 0.01). CONCLUSION: In our analysis, patients who received SRS with nivolumab and ipilimumab had superior LC without increased risk of toxicity or compromised immunotherapy treatment completion despite the SRS cohort having higher rates of prior immunotherapy. Further prospective study of combination nivolumab and ipilimumab with SRS is warranted.