Number Of Brain Metastases Research Articles

A Scoring Tool to Estimate the Survival of Elderly Patients With Brain Metastases from Esophageal Cancer Receiving Whole-brain Irradiation.

Elderly patients with metastatic esophageal cancer may benefit from individualized therapies. A tool to predict the survival of such patients with brain metastases was created. In 11 elderly patients (≥65 years) receiving whole-brain irradiation (WBI) for brain metastases from esophageal cancer, age, gender, performance status, number of brain metastases, metastases outside the brain, time between cancer diagnosis and WBI, and WBI regimen were evaluated for survival. On univariate analyses, age ≥73 years (p=0.046) and time between diagnosis of esophageal cancer and WBI ≤6 months (p=0.046) were significantly associated with poorer survival. On multivariate analysis, both showed a trend. Based on these two factors, the following points were assigned: age ≤72 years=1 point, age ≥73 years=0 points; time between cancer diagnosis and WBI >6 months=1 point, and ≤6 months=0 points. Three prognostic groups were thus formed: 0, 1 and 2 points. Survival rates of these groups at 6 months were 0%, 0% and 40% (p=0.012), respectively. This new tool allows estimation of survival and treatment individualization in elderly patients irradiated for brain metastases from esophageal cancer.

Prognosis and Treatment Outcomes of Patients Undergoing Resection of Brain Metastases from Breast Cancer.

Brain metastases from breast cancer have poor prognosis and are a challenge to treat. Multiple treatment options are available. Descriptive and prognostic data on breast cancer brain metastases is limited. This study analyzed clinical data of patients who underwent surgical resection of one or more brain metastases. Histological and clinical characteristics, as well as treatment modalities, were analyzed. Initial tumor stage or grade was found not to correlate with the median time to developing brain metastases or survival. Human epidermal growth factor receptor 2 (HER2)-positive status was not associated with shorter median time to developing brain metastases. No correlation was found between the number of brain metastases and patient outcome. Results confirm the survival benefit of surgical resection with or without irradiation. Data showed that patients with HER2-positive and those with triple-negative breast cancer develop brain metastases at lower stages but not earlier after diagnosis, and survival is mostly dependent on treatment modality rather than histological subtype.

Abstract P2-20-08: Validation and comparison of breast graded prognostic assessment score and modified breast graded prognostic assessment in patients with brain metastases as prognostic tool

Abstract Background: Brain metastases (BM) occur in 15-35% of patients (p) with metastatic breast cancer (MBC), confering bad prognosis and the major limitation of life expectancy and quality of life. Nevertheless, there is a wide prognostic spectrum within this group of p. Clinical scores have been developed trying to classify according to its prognosis. Initially, the Breast Graded Prognostic Assessment (B-GPA, Sperduto et al, 2012) Then, it was adapted by adding the number of brain metastases, which is called modified Breast Graded Prognostic Assessment (mB-GPA, Subbiah et al 2015). We tried to validate these scores and compare them to determine which is the best prognostic predictor tool. Method: This is an ambispective study including all patients diagnosed of breast cancer’s brain metastases treated in a single cancer comprehensive center. Identification of patients and updates of follow up were performed through Radiation Oncology department registries and Pathology records. Both clinical and pathological data were collected. B-GPA and mB-GPA were calculated for each P. We analyze the survival after BM (SaBM) determining it as the time from the moment of diagnosis of the BM until the death due to the disease or any other cause. The Kaplan-Meier method was used to calculate SaBM and the univariate analyses was conducted using the Cox proportional hazard regression model. ROC curves were performed to compare both scores. Results: We included 169 P with a median age of 50 years (29-81). At last follow-up (April 2019) 90% of the P had died. Histological subtypes: 41.8% were luminal-like, 36.1% Her2 positive and 22% triple negative tumors. 25% of these P were diagnosed with stage IV. Nineteen percent of p presented only BM as the first site of relapse. A third of the P presented more than 3 brain metastases. WBRT was applied to 68.2% P, while stereotactic radiosurgery and surgery was performed in 18.2% and 18.2% respectively. The median SaBM was 12 months (m) (95% Confidence Interval (CI) [8.0-16.0m]. In the univariated analysis SaBM was longer in Her2 P than Luminal and TN P (26 m vs 11m and 8m p=0.01). Regarding the number of lesions, more than 3 present worse survival than p with 2-3 and only one metastasis (8m vs 11m vs 22m p=0.046). In the univariated analysis B-GPA and mGPA showed significant correlation with prognosis. Patients in group 4 of B-GPA (3.5-4 points) presented a better SaBM than the other groups, being statistically significant (see table 1) Likewise, group 4 of mB-GPA (3.5-4 points) showed a better stadistically significant survival (see table 1). The ROC curves showed that GPA and mGPA have very similar prognostic capabilities, perhaps slightly in favor of modified GPA (GPA: 0.269 and mGPA: 0.286) Conclusion: Our series validates the previous results regarding the GPA scores that allow discriminating risk groups with significant different survival. In our series mB-GPA was slightly better predictor of prognostic. In the univariate analysis B-GPA and mB-GPA, number of lesions and histological subtypes were the most important prognosis factors for MBC patients with BM. This situation can allow us to choose and better adjust the therapeutic effort in each patient, which has to be valued by a multidisciplinary team. Table 1: SaBM regarding GPA scoresB-GPA(group)N°SaBM (months)CI 95% (m)p value0-1 (1)580-18.91.5-2 (2)2164.5-7.52.5-3 (3)29199.3-28.63.5-4 (4)263626.7-46.2p=<0.001mB-GPA (group)N°SaBM (months)CI 95% (m)p value0-1 (1)1040-10.71.5-2 (2)3072.5-11.52.5-3 (3)352717.5-36.53.5-4 (4)73733.5-40.5p=<0.001 Citation Format: Carles Fabregat Franco, Agostina Stradella, Valentin Navarro, Jennifer Linares, Sabela Recalde Peñabad, Roser Velasco Fargas, Marta Simó Parra, Adela Fernandez Ortega, Andrea Vethencourt, Catalina Falo Zamora, Silvia Vazquez Fernandez, Rafael Villanueva Vazquez, Manuel Galdeano, Miguel Gil-Gil. Validation and comparison of breast graded prognostic assessment score and modified breast graded prognostic assessment in patients with brain metastases as prognostic tool [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-20-08.

Validation of the graded prognostic assessment for gastrointestinal cancers with brain metastases (GI-GPA)

PurposeThe purpose of this study was to validate a new prognostic model (GI-GPA) originally derived from a multi-center database (USA, Canada, Japan).Patients and MethodsThis retrospective study included 92 German and Norwegian patients treated with individualized approaches, always including brain radiotherapy. Information about age, extracranial spread, number of brain metastases, performance status and other variables was collected. The GI-GPA score was calculated as described by Sperduto et al.ResultsMedian survival was 4 months. The corresponding figures for the 4 different prognostic strata were 2.3, 4.4, 9.4 and 12.7 months, respectively (p = 0.0001). Patients whose management included surgical resection had longer median survival than those who were treated with other approaches (median 11.9 versus 3.0 months, p = 0.002). Comparable results were seen for additional systemic therapy (median 8.5 versus 3.5 months, p = 0.01).ConclusionThese results confirm the validity of the GI-GPA in an independent dataset from a different geographical region, despite the fact that overall survival was shorter in all prognostic strata, compared to Sperduto et al. Potential explanations include differences in molecular tumor characteristics and treatment selection, both brain metastases-directed and extracranially. Long-term survival beyond 5 years is possible in a small minority of patients.

The Results of Whole-brain Radiotherapy for Elderly Patients With Brain Metastases from Urinary Bladder Cancer.

The number of elderly patients with cancer is growing and requires particular attention. These patients may benefit from personalized treatments. This study aimed to identify prognostic factors of survival for elderly patients (≥65 years) irradiated for brain metastases from urinary bladder cancer. In 29 elderly patients treated with whole-brain radiotherapy (WBRT), seven factors were retrospectively analyzed regarding survival, namely dose-fractionation regimen, age, gender, Karnofsky performance score, number of brain metastases, extra-cranial metastases, and interval between cancer diagnosis and WBRT. For the whole series, survival was 38% at 3 months and 21% at 6 months. Karnofsky performance score ≥70% showed a trend for being associated with improved survival when compared to ≤60%; survival rates were 50% vs. 29% at 3 months and 33% vs. 12% at 6 months (p=0.18). Karnofsky performance score may help estimate the survival of elderly patients irradiated for brain metastases from urinary bladder cancer.

Hemorrhagic and Cystic Brain Metastases Are Associated With an Increased Risk of Leptomeningeal Dissemination After Surgical Resection and Adjuvant Stereotactic Radiosurgery.

Brain metastases (BM) treated with surgical resection and focal postoperative radiotherapy have been associated with an increased risk of subsequent leptomeningeal dissemination (LMD). BMs with hemorrhagic and/or cystic features contain less solid components and may therefore be at higher risk for tumor spillage during resection. To investigate the association between hemorrhagic and cystic BMs treated with surgical resection and stereotactic radiosurgery and the risk of LMD. One hundred thirty-four consecutive patients with a single resected BM treated with adjuvant stereotactic radiosurgery from 2008 to 2016 were identified. Intracranial outcomes including LMD were calculated using the cumulative incidence model with death as a competing risk. Univariable analysis and multivariable analysis were assessed using the Fine & Gray model. Overall survival was analyzed using the Kaplan-Meier method. Median imaging follow-up was 14.2 mo (range 2.5-132 mo). Hemorrhagic and cystic features were present in 46 (34%) and 32 (24%) patients, respectively. The overall 12- and 24-mo cumulative incidence of LMD with death as a competing risk was 11.0 and 22.4%, respectively. On multivariable analysis, hemorrhagic features (hazard ratio [HR] 2.34, P=.015), cystic features (HR 2.34, P=.013), breast histology (HR 3.23, P=.016), and number of brain metastases >1 (HR 2.09, P=.032) were independently associated with increased risk of LMD. Hemorrhagic and cystic features were independently associated with increased risk for postoperative LMD. Patients with BMs containing these intralesion features may benefit from alternative treatment strategies to mitigate this risk.

EP1.16-44 Survival and Prognostic Association of Non-Small Cell Lung Cancer with Brain Metastases After WBRT: A Multicentre Study

Forty percent of intracranial tumors are metastatic, arising most commonly from lung. To our knowledge, no data is available on prognosis factors of the survival of non-small cell lung cancer (NSCLC) patients with brain metastases in Bangladesh. This study aims to determine overall survival (OS) and identify prognosis factors in NSCLC patients with brain metastases after whole brain radiation therapy (WBRT). The study retrospectively investigated histologically proven NSCLC patients with brain metastases at two tertiary hospitals in Bangladesh from January, 2013 to April, 2018. A total of 62 patients were eligible who received 30 Gy (3 Gy per fraction) of WBRT. The primary end point was OS and the secondary endpoint was prognostic association with various factors including patient age and gender, tumor histology, Karnofsky performance status, pleural effusion, primary not controlled, extracranial metastases, the number of brain metastases, surgical resection and diagnosed initially with brain metastases or developed brain metastases later. RTOG Recursive Partitioning Analysis (RPA) was used to categorize the patients. Survival was calculated by Kaplan-Meier method and compared by Log-rank test. Prognostic association was evaluated with Cox proportional hazards model analysis. Mean survival of the entire cohort was 5.76 months (95% CI: 4.69 – 6.84 months). Patients with brain metastases at diagnosis or developed brain metastases later during disease progression had a statistically similar mean survival (6.18 months vs. 5.49 months; P = 0.422). Among the 62 patients, 16.1%, 30.6% and 53.2% were RPA Class I, II and III respectively. Mean survival differed significantly among the three classes (Class I: 9.10 months, Class II: 6.68 months, Class III: 3.64 months; P = 0.00). Individual prognostic factors were not found to be associated with survival difference except, single vs. multiple brain metastases (P = 0.042) and primary controlled or not (P = 0.026). The study reported survival time of NSCLC patients with brain metastases undergo WBRT, and indicated that higher RPA classes, primary not controlled and greater numbers of brain metastatic lesions are the three prognostic factors of poor survival for this cohort. Our results may help clinicians in patient counseling, treatment selection and designing future clinical trials.

SURG-12. A COMPARISON BETWEEN PROGNOSTIC SCORES OF BREAST CANCER BRAIN METASTASES APPLIED TO A NEUROSURGICAL POPULATION

INTRODUCTION: Prognostic scores have been developed to predict overall survival (OS) in patients with brain metastasis from breast cancer, comprising different combinations of prognostic factors. A new prognostic score including the number of brain metastases has been proposed. We aimed to evaluate the use of these prognostic scores on a neurosurgical population. METHODS: Retrospective study with consecutive patients with brain metastasis from breast cancer treated in the neurosurgery department. Clinical end point is overall survival estimated by the Kaplan Meier method. Univariate and multicovariate Cox proportional hazard models are applied to estimate the effect of covariates of interest on OS. We employ Bootstrap validation method to estimate the bias-corrected or over fitting-corrected predictive accuracy of Cox models, which is presented by concordance index(C-index). RESULTS: 315 consecutive patients with brain metastasis from breast cancer. Median OS was 14 months(95% CI 11–16.9), KPS, number of brain metastases, biological subtypes, age and presence of extracranial metastases were significantly associated with improved OS on the univariate analysis. Multivariate analysis showed that KPS, biological subtype, age and number of brain metastases were statistically significant for OS. The recursive partitioning analysis(RPA) classes, the graded prognostic assessment(GPA) score, the diagnostic specific GPA(DS-GPA) and the modified DS-GPA identified individual subgroups with different OS. RPA and DS-GPA had OS statistical significant between all groups with a C-index of 0.561 and 0.586 respectively. DS-GPA had a c-index of 0.639 and modified DS-GPA had an c-index of 0.637. DS-GPA and modified DS-GPA had a better performance in terms of discrimination when compared to RPA(p< 0.001) and GPA(p=0.01). CONCLUSIONS: DS-GPA and modified DS-GPA were able to better discriminate subgroups OS, which most likely reflects the use of biological subtype in the score calculation. The incorporation of number of BM by the modified DS-GPA improved the distinction between the higher score and the lower score group.

RADI-01. PROGNOSTIC FACTORS OF SHORT SURVIVAL FOR BRAIN METASTASES TREATED WITH SRS WITHOUT WBRT.

Nowadays multiple brain metastases (up to 10–15 tumors) are treated with SRS alone. The most common diagnosis-specific Graded Prognostic Assessment and Score for Radiosurgery indices are based on data regarding limited brain metastases (1–4). Moreover, many of patients included in that analyses were treated with WBRT or combination of WBRT and SRS and some relevant data were not included due to a retrospective analysis of large datasets. SRS may increase intracranial control of disease, however, treatment of patients with a prognosis of fewer than 3 months survival after SRS may not be clinically reliable. Therefore we conducted an analysis of prospective registry to find the factors that correlate with very short survival after SRS. Materials and methods, A consecutive cohort of 84 patients treated with SRS only for brain metastases between 04.2018-03.2019. Data prospectively collected and introduced into a registry of patients treated with SRS in our department were analyzed. The analyzed factors are age, primary site, histopathology, previous surgery, molecular results, systemic therapy, duration of SRS planning, the extent of extracerebral metastatic disease, number of brain metastases, mass effect and neurological symptoms/ We performed a univariate analysis and multivariate Cox regression model to find a correlation between clinical and molecular data and survival in brain metastases patients treated with SRS only. Factors predicted early death and correlated with survival will be presented at the conference

Prognostic factors of brain metastases from colorectal cancer

BackgroundFor brain metastases from non-specific primary tumors, the most frequently used and validated clinical prognostic assessment tool is Karnofsky performance status (KPS). Given the lack of prognostic factors of brain metastases from colorectal cancer (CRC) other than KPS, this study aimed to identify new prognostic factors.MethodsThis retrospective cohort study was conducted at a tertiary care cancer center. Subjects were patients with brain metastases from CRC among all patients who received initial treatment for CRC at the National Cancer Center Hospital from 1997 to 2015 (n = 7147). Prognostic clinicopathological variables for overall survival (OS) were investigated.ResultsThere were 68 consecutive patients with brain metastases from CRC, corresponding to 1.0% of all patients with CRC during the study period. Median survival time was 6.8 months. One-year and 3-year OS rates were 28.0 and 10.1%, respectively. Among the six covariates tested (age, KPS, presence of extracranial metastases, control of primary lesion, number of brain metastases, and history of chemotherapy), multivariate analysis revealed KPS (score ≥ 70), number of brain metastases (1–3), and no history of chemotherapy to be independent factors associated with better prognosis.ConclusionsIn addition to KPS, the number of brain lesions and history of chemotherapy were independent prognostic factors for OS in patients with brain metastases from CRC. An awareness of these factors may help gastrointestinal surgeons make appropriate choices in the treatment of these patients.

Prognostic Role of Pre-Treatment Symptoms for Survival of Patients Irradiated for Brain Metastases.

For treatment of brain metastases, a patient's survival prognosis should be considered. Existing survival scores appear complex and require complete tumor staging. For many patients, a faster and simpler tool would be helpful. This retrospective study investigated the prognostic value of the number of pre-treatment symptoms plus eight other factors on survival of patients irradiated for brain metastases. Other factors included whole-brain radiotherapy (WBRT) regimen, age, gender, performance score, primary tumor type, number of brain metastases, extracranial metastases, and interval between cancer diagnosis and WBRT. The number of symptoms (p=0.002) and all other factors were significantly associated with survival on univariate analyses. On multivariate analysis, all factors but the number of symptoms (p=0.47) and primary tumor type (p=0.48) were significant. Since the number of symptoms was not an independent predictor of survival, it cannot replace existing scoring tools and may only serve for orientation.

Abstract 4867: Radiosurgery consultation to treatment interval, additional brain metastases during the interim and outcomes after therapy

Abstract Background: Expediting the process of diagnosis and treatment should theoretically improve outcome. Delays in beginning therapy can cause anxiety to the patients and physicians who may be concerned about tumor progression before treatment is initiated. Treatment delays can be characterized as patient-generated or logistical medical infrastructure prolongations. Objective: The goal of the present study was to determine the impact of stereotactic radiosurgery (RS) consultation to treatment interval (CTI) and the development of additional brain metastases (BRM) during the interim on outcomes after RS. Methods: Between October 2014 and April 2018, 15 individuals developed more contrast-enhancing BRMs during the CTI. These patients were treated with gamma knife RS (including the six patients who underwent gross resection of metastatic intracranial neoplasm). The median duration of CTI was 19 days (range 5-61 days). A comparison of the ≤19 days CTI (eight patients) to the &amp;gt;19 days CTI (seven patients) was performed to assess the effects of the extent of delay to RS. The total number of BRM for RS was 68. The median target volume was 0.48 cm3, and the median margin dose was 24 Gy. Results: Most (67%) of the subjects exhibited good performance status. The overall crude survival rate at two years was 27%; acute or late toxicity after RS was not observed. Comparison of the CTI groups revealed: i) A longer CTI was not associated with a poorer prognosis; ii) BRM recurrence after RS was less common in this patient subgroup; iii) Quality of life (QOL) was satisfactory even though the CTI was prolonged. Conclusion: Acceptable longevity with minimal morbidity satisfying the QOL consideration was found in this audit of cases about CTI and the occurrence of more BRMs during the interim. Decreasing CTI in patients with BRM remains an important goal of quality improvement. Citation Format: Federico Ampil, Gloria Caldito, Troy Richards. Radiosurgery consultation to treatment interval, additional brain metastases during the interim and outcomes after therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4867.

Seizure prevalence, contributing factors, and prognostic factors in patients with leptomeningeal disease

BackgroundTo determine seizure prevalence and contributing factors in patients with leptomeningeal disease (LMD). MethodsAuthors performed a retrospective review of 79 consecutive patients with a diagnosis of LMD. Associations between categorical variables were assessed using Chi-Square tests or Fisher's Exact tests. Survival was plotted with Kaplan Meier curves. Variables with a log-rank p-value of <0.20 were entered into a Cox Proportional Hazard regression analysis. ResultsSeizure prevalence in those with and without brain metastases was 22%. Of those who seized, 65% were admitted for this at least once while only one patient required intubation. Primary malignancy, type or route of chemotherapy administration, form of radiation therapy (craniospinal, focal, or whole brain), surgical treatment, location of LMD, and number of brain metastases did not influence seizure development. Only 13% of patients who never had seizures were on a prophylactic AED (anti-epileptic drug). In patients who had brain metastasis, there was no significant difference in prevalence of seizure before versus after LMD diagnosis suggesting that LMD does not significantly increase the risk of seizure compared to brain metastasis alone. A multivariate analysis revealed that while males trended toward inferior survival, only performance status and treatment with systemic chemotherapy showed a significant association with survival. Median survival time of patients after LMD diagnosis was four months. ConclusionThe prevalence of seizure in LMD patients is 22%. There were no statistically significant predisposing factors to seizure development. ECOG and use of systemic chemotherapy were found to be significant prognostic factors.

Results of surgical resection in lung cancer with synchronous brain metastasis.

This study aims to investigate the factors affecting the survival of operated non-small cell lung cancer patients with synchronous brain metastasis. Clinical outcomes of a total of 16 patients (14 males, 2 females; mean age 60 years; range, 41 to 71 years) who were diagnosed with non-small cell lung cancer and concomitant solitary/oligo brain metastasis and who underwent an intervention primarily for cranium, followed by lung resection in our clinic between January 2012 and January 2016 were retrospectively analyzed. Cranial surgery or gamma-knife radiosurgery was performed in the treatment of brain metastases. Twelve patients with solitary brain metastasis underwent cranial surgery, while four patients with solitary/oligo metastases underwent gamma-knife radiosurgery prior to pulmonary resection. Definitive pathological examination revealed adenocarcinoma in 13 patients and squamous-cell lung carcinoma in three patients. Mean survival time was 15.3±8.6 months. One-year and two-year survival rates were 56.2% and 32%, respectively. The number of brain metastases, treatment type, tumor cell type, resection type, and status of lymph nodes were not statistically significantly associated with survival (p>0.05). Cranial surgery or gamma-knife radiosurgery followed by aggressive lung resection can be effectively applied in selected non-small cell lung cancer patients with synchronous brain metastasis. However, the suitability of the primary tumor and brain metastases for complete resection is of utmost importance in patient selection.

MON-554 Brain Metastases in Thyroid Cancer: Molecular Profile and Institutional Experience of a Single Tertiary Referral Center in the Era of Kinase Inhibitor Therapy

Background: Historical data suggests differentiated thyroid cancer (DTC) patients (pts) with brain metastases (mets) have overall survival (OS) of approximately 1 year; other reports refer median OS of 33months. Little is known about the mutation profile these pts. The TCGA indicates a median of 1 mutation in pts with PTC, most of which were low risk cases. Methods: We retrospectively studied clinical characteristics including number of lesions, therapeutic modalities, OS and mutational profile of TC pts with brain mets at a single cancer center between 2013-2018. Cases were identified by ICD-9 & -10 codes for TC and secondary neoplasm of brain but excluded if a separate malignancy accounted for brain mets. Somatic mutations were tested by targeted next-generation sequencing in the majority of cases. Results: Of 105 cases reviewed, 52 met entry criteria. Median age at diagnosis of brain mets was 62.5 years (4-85years); 31/52 (59.6%) were males. DTC accounted for the majority of the pts, 37/52 (71%) [papillary thyroid cancer 55.8%(PTC; 29/52); poorly differentiated thyroid cancer (PDTC; 5/52) 9.6%; follicular thyroid cancer 5.8% (3/52); Hurthle cell 0/52]; anaplastic thyroid cancer (ATC) 21.1% (11/52) & medullary thyroid cancer 7.7% (4/52). Symptoms were present in 50%, predominantly weakness 9/26 (34.6%), headaches 6/26 (23.1%), altered mental status 5/26 (19.2%), visual changes 5/26 (19.2%) and seizures 4/26 (15.4%). 47 pts received systemic therapy as follows: antiangiogenic drug 26/47 (55%); BRAF inhibitor alone or in combination with MEK inhibitor 22/47 (46.8%) and checkpoint inhibitors 16/47 (34%). Molecular testing was available in 50 cases. Known oncogenic driver mutations were noted in 86%(43/50); BRAF V600E mutated in 25/50 (50%), RAS 14/50 (28%; NRAS n=11, HRAS n=2, KRAS n=1), RET mutated in 4 cases. Of 25 pts tested for TERT promoter mutation 8 (32%) were positive. Mean number +/- SD of somatic mutations was 2.14 +/- 1.15 in PTC; 2.6 +/-1.62 in PDTC; and 5.45 +/- 4.6 in ATC. In terms of number of brain lesions, 38.5% had ≥3 metastatic foci. Treatment consisted of radiation [stereotactic radiosurgery 22/50 (44%), whole brain radiation 10/50 (20%)] and 13/50 (26%) surgical intervention. Median OS was 29.7 months (95% CI 12.5-NR) after brain mets diagnosis. 1-year survival by number of brain metastases was 76% for single focus (n=17), 66% for 2 (n=15) and 50% (n=20) for ≥3 (p=0.034). One year OS for surgically treated vs radiation was not statistically different. 1-year OS for DTC was 65% (95% CI 51%, 82%) vs 53% in ATC (95% CI 30%, 94%) p-value=0.996. The OS in symptomatic vs silent brain mets was 19.9 months vs 29.6 months (p value= 0.45). Conclusions: Mutation burden appears to be higher in TC pts with brain mets compared to TCGA. In TC pts with brain mets, survival decreases as number of lesions increases. The OS was slightly shorter in pts with symptomatic brain mets but not statistically significant.

Optimal Sequence of Local and EGFR-TKI Therapy for EGFR-Mutant Non-Small Cell Lung Cancer With Brain Metastases Stratified by Number of Brain Metastases

It is unclear whether local therapy (LT) or epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) should take precedence for patients with EGFR-mutant non-small cell lung cancer (NSCLC) and brain metastases (BMs). The number of BMs is important in the choice of LT, including whole-brain radiation therapy, stereotactic radiosurgery, and surgery. We retrospectively evaluated cases of EGFR-mutant non-small cell lung cancer with BMs from a single site. Patients were divided into 2 groups based on upfront therapy-EGFR-TKI (TKI) or LTs-and subsequently stratified by the number of BMs. Among 176 patients, 61% received upfront EGFR-TKI, and 39% received upfront LT. The number of patients with 1 to 4 BMs was similar (56% vs 52%; P=.61). All patients with 1 to 4 BMs in the LT group, except for surgical cases, received stereotactic radiosurgery (n=31). Among those with ≥5 BMs, most (n=27; 82%) received whole-brain radiation therapy. There was no significant difference in OS between LT and TKI groups (median overall survival, 28 vs 23months; hazard ratio, 0.75; 95% confidence interval, 0.52-1.07). In patients with 1 to 4 BMs, the LT group showed significantly better OS compared with the TKI group (median overall survival, 35 vs 23months; hazard ratio, 0.54; 95% confidence interval, 0.32-0.90). There was no difference in OS between the LT and TKI groups for patients with ≥5 BMs. Multivariable analysis showed that upfront LT yielded significantly better OS for patients with 1 to 4 BMs. Upfront LT followed by EGFR-TKI is more effective than upfront EGFR-TKI for the survival of untreated patients harboring EGFR mutations with 1 to 4 BMs.

Comparing the efficacy of concurrent EGFR-TKI and whole-brain radiotherapy vs EGFR-TKI alone as a first-line therapy for advanced EGFR-mutated non-small-cell lung cancer with brain metastases: a retrospective cohort study.

BackgroundNon-small-cell lung cancer (NSCLC) is a global public health problem, and brain is a common metastatic site in advanced NSCLC. Currently, whole-brain radiotherapy (WBRT) remains a major treatment for brain metastases, while EGFR-tyrosine kinase inhibitor (TKI) is the standard treatment for advanced NSCLC harboring EGFR mutations, which is also effective for brain metastases. However, whether EGFR-TKIs plus radiotherapy is superior to EGFR-TKIs alone for the treatment of advanced EGFR-mutant NSCLS with brain metastases remains controversial. This study aimed to compare the efficacy of concurrent EGFR-TKIs and WBRT vs EGFR-TKI alone in a retrospective cohort of advanced EGFR-mutant NSCLS with brain metastases.Patients and methodsThe medical records of 104 treatment-naïve, advanced EGFR-mutant NSCLC patients with brain metastases were retrospectively reviewed, and there were 56 patients undergoing concurrent EGFR-TKI and WBRT, and 48 patients given EGFR-TKI alone, including 20 cases with salvage WBRT upon brain metastasis progression. The survival prognosis was compared between the two cohorts.ResultsThe baseline clinicopathologic factors were balanced between the two cohorts. After a median follow-up of 23 months, 35.6% of the study subjects survived. Concurrent EGFR-TKI and WBRT significantly improved the median intracranial PFS (iPFS) compared with EGFR-TKI alone (17.7 vs 11.0 months, P=0.015); however, no significant difference was seen in median overall survival between the two cohorts (28.1 vs 24.0 months, P=0.756). In addition, the median iPFS was found to significantly vary in the number of brain metastases (≤3 vs>3 metastases: 18.0 vs 12.5 months, P=0.044). Subgroup analysis showed that concurrent EGFR-TKI and WBRT improved median iPFS compared with EGFR-TKI alone in patients with more than three brain metastases (P=0.001); however, no significant difference was observed between the two regimens in patients with three or less brain metastases (P=0.526).ConclusionOur data demonstrate that concurrent EGFR-TKI and WBRT achieves longer iPFS than EGFR-TKI alone in advanced EGFR-mutant NSCLC with brain metastases. In advanced EGFR-mutant NSCLC with three or less brain metastases, EGFR-TKI alone may be an option as a first-line therapy.

Does Stereotactic Radiosurgery Have a Role in the Management of Patients Presenting With 4 or More Brain Metastases?

Stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) are effective treatments for management of brain metastases. Prospective trials comparing the 2 modalities in patients with fewer than 4 brain metastases demonstrate that overall survival (OS) is similar. Intracranial failure is more common after SRS, while WBRT is associated with neurocognitive decline. As technology has advanced, fewer technical obstacles remain for treating patients with 4 or more brain metastases with SRS, but level I data supporting its use are lacking. Observational prospective studies and retrospective series indicate that in patients with 4 or more brain metastases, performance status, total volume of intracranial disease, histology, and rate of development of new brain metastases predict outcomes more accurately than the number of brain metastases. It may be reasonable to initially offer SRS to some patients with 4 or more brain metastases. Initiating therapy with SRS avoids the acute and late sequelae of WBRT. Multiple phase III trials of SRS vs WBRT, both currently open or under development, are directly comparing quality of life and OS for patients with 4 or more brain metastases to help answer the question of SRS appropriateness for these patients.

Comparison of Diagnosis-Specific Survival Scores for Patients with Small-Cell Lung Cancer Irradiated for Brain Metastases.

Diagnosis-specific survival scores including a new score developed in 157 patients with brain metastases from small-cell lung cancer (SCLC) receiving whole-brain radiotherapy (WBRT) with 30 Gy in 10 fractions (WBRT-30-SCLC) were compared. Three prognostic groups were designed based on the 6-month survival probabilities of significant or almost significant factors, (age, performance score, number of brain metastases, extra-cerebral metastasis). Six-month survival rates were 6% (6–11 points), 44% (12–14 points) and 86% (16–19 points). The WBRT-30-SCLC was compared to three disease-specific scores for brain metastasis from SCLC, the original and updated diagnosis-specific graded prognostic assessment DS-GPA classifications and the Rades-SCLC. Positive predictive values (PPVs) used to correctly predict death ≤6 months were 94% (WBRT-30-SCLC), 88% (original DS-GPA), 88% (updated DS-GPA) and 100% (Rades-SCLC). PPVs to predict survival ≥6 months were 86%, 75%, 76% and 100%. For WBRT-30-SCLC and Rades-SCLC, differences between poor and intermediate prognoses groups and between intermediate and favorable prognoses groups were significant. For both DS-GPA classifications, only the difference between poor and intermediate prognoses groups was significant. Of these disease-specific tools, Rades-SCLC appeared to be the most accurate in identifying patients dying ≤6 months and patients surviving ≥6 months after irradiation, followed by the new WBRT-30-SCLC and the DS-GPA classifications.

Detectability of Brain Metastases by Using Frequency-Selective Nonlinear Blending in Contrast-Enhanced Computed Tomography.

The aim of this study to evaluate the role of frequency-selective nonlinear blending (FS-NLB) for the detectability of brain metastases with contrast-enhanced computed tomography (CECT) using magnetic resonance imaging (MRI) as standard of reference. A retrospective patient data search at our institution yielded 91 patients who underwent both brain CECT and MRI for screening of brain metastases (n = 173) between 2014 and 2016 (mean time interval, 29 ± 37 [malignant: 15 ± 16/benign: 42 ± 47] days). A recently introduced FS-NLB postprocessing technique was applied to CECT images. Two readers interpreted all CT images in an independent fashion. The conventional, linear blending (LB) CT images were evaluated first. After a washout period, the same readers evaluated the FS-NLB CT images. The standard of reference was established by a consensus interpretation of the brain MRI studies. Outcome variables included determination of best performing FS-NLB settings, region of interest (ROI)-based calculation of contrast-to-noise ratios (CNRs), size, and number of brain metastases. Based on the number of metastases, we classified patients in 5 therapeutically relevant categories (0, no metastasis; 1, singular metastasis; 2, less than 4 metastases; 3, >4 and <10 metastases; 4, >10 metastases). Statistical comparison and diagnostic performance tests were applied. A center of 47 Hounsfield units (HU), delta of 5 HU, and slope of 5 resulted in the best delineation of hyperdense brain metastases, whereas for hypodense brain metastases, a center of 32 HU, delta of 5 HU, and slope of 5 showed best delineation. Frequency-selective nonlinear blending significantly increased CNR in hyperdense cerebral metastases (CECT: 9.11 [6.9-10.9], FS-NLB: 18.1 [11.9-22.8]; P < 0.0001) and hypodense cerebral metastases (CECT: 6.3 [5.2-8], FS-NLB: 17.8 [14.5-19.7]; P < 0.0001). Sensitivity, specificity, negative predictive values, positive predictive values, and accuracy for LB, and FS-NLB were 40%, 98%, 99%, 31%, and 52%, and 62%, 94%, 97%, 40%, and 69%, respectively. Magnetic resonance imaging, LB, and FS-NLB classification of metastatic patients were group 0 (47, 47, 46), group 1 (14, 8, 11), group 2 (16, 12, 15), group 3 (8, 7, 8), and group 4 (6, 4, 6). Frequency-selective nonlinear blending postprocessing of CECT significantly increases the detection of brain metastases over conventional CECT; however, the sensitivity remains lower than MRI. Frequency-selective nonlinear blending is slightly inferior in the categorization of patients into therapeutically relevant groups, when compared with MRI.