Graded Prognostic Assessment Score Research Articles

Immunotherapy combined with cranial radiotherapy for driver-negative non-small-cell lung cancer brain metastases: a retrospective study.

Background: This study assesses immune checkpoint inhibitors' efficacy for non-small-cell lung cancer (NSCLC) with brain metastases (BM) and explores the role of cranial radiation therapy (CRT) in the immunotherapy era. Methods: The retrospective analysis screened NSCLC patients with BMs from July 2018 to December 2021. Treatment involved chemotherapy combined with immune checkpoint inhibitors as the first-line, with patients divided into CRT and non-CRT groups. Overall survival (OS), progression-free survival and intracranial progression-free survival were calculated and compared. Results: Among 113 patients, 74 who received CRT had significantly better median OS (not reached vs 15.31months), particularly among those with one to three BMs. Factors correlating with better OS included CRT, PD-L1 expression and diagnosis-specific graded prognostic assessment scores. Conclusion: Integrating CRT with anti-PD-1 therapy notably enhanced long-term survival in NSCLC patients with BMs.

168P Validation of lung specific and lung molecular graded prognostic assessment score in metastatic NSCLC with brain metastases from India

168P Validation of lung specific and lung molecular graded prognostic assessment score in metastatic NSCLC with brain metastases from India

Navigating Post-Operative Outcomes: A Comprehensive Reframing of an Original Graded Prognostic Assessment in Patients with Brain Metastases.

Graded Prognostic Assessment (GPA) has been proposed for various brain metastases (BMs) tailored to the primary histology and molecular profiles. However, it does not consider whether patients have been operated on or not and does not include surgical outcomes as prognostic factors. The residual tumor burden (RTB) is a strong predictor of overall survival. We validated the GPA score and introduced "volumetric GPA" in the largest cohort of operated patients and further explored the role of RTB as an additional prognostic factor. A total of 630 patients with BMs between 2007 and 2020 were included. The four GPA components were analyzed. The validity of the original score was assessed using Cox regression, and a modified index incorporating RTB was developed by comparing the accuracy, sensitivity, specificity, F1-score, and AUC parameters. GPA categories showed an association with survival: age (p < 0.001, hazard ratio (HR) 2.9, 95% confidence interval (CI) 2.5-3.3), Karnofsky performance status (KPS) (p < 0.001, HR 1.3, 95% CI 1.2-1.5), number of BMs (p = 0.019, HR 1.4, 95% CI 1.1-1.8), and the presence of extracranial manifestation (p < 0.001, HR 3, 95% CI 1.6-2.5). The median survival for GPA 0-1 was 4 months; for GPA 1.5-2, it was 12 months; for GPA 2.5-3, it was 21 months; and for GPA 3.5-4, it was 38 months (p < 0.001). RTB was identified as an independent prognostic factor. A cut-off of 2 cm3 was used for further analysis, which showed a median survival of 6 months (95% CI 4-8) vs. 13 months (95% CI 11-14, p < 0.001) for patients with RTB > 2 cm3 and <2 cm3, respectively. RTB was added as an additional component for a modified volumetric GPA score. The survival rates with the modified GPA score were: GPA 0-1: 4 months, GPA 1.5-2: 7 months, GPA 2.5-3: 18 months, and GPA 3.5-4: 34 months. Both scores showed good stratification, with the new score showed a trend towards better discrimination in patients with more favorable prognoses. The prognostic value of the original GPA was confirmed in our cohort of patients who underwent surgery for BM. The RTB was identified as a parameter of high prognostic significance and was incorporated into an updated "volumetric GPA". This score provides a novel tool for prognosis and clinical decision making in patients undergoing surgery. This method may be useful for stratification and patient selection for further treatment and in future clinical trials.

Adding simultaneous integrated boost to whole brain radiation therapy improved intracranial tumour control and minimize radiation-induced brain injury risk for the treatment of brain metastases

BackgroundBrain metastases (BMs) are the most frequent intracranial tumours associated with poor clinical outcomes. Radiotherapy is essential in the treatment of these tumours, although the optimal radiation strategy remains controversial. The present study aimed to assess whether whole brain radiation therapy with a simultaneous integrated boost (WBRT + SIB) provides any therapeutic benefit over WBRT alone.MethodsWe included and retrospectively analysed 82 patients who received WBRT + SIB and 83 who received WBRT alone between January 2012 and June 2021. Intracranial progression-free survival (PFS), local tumour control (LTC), overall survival (OS), and toxicity were compared between the groups.ResultsCompared to WBRT alone, WBRT + SIB improved intracranial LTC and PFS, especially in the lung cancer subgroup. Patients with high graded prognostic assessment score or well-controlled extracranial disease receiving WBRT + SIB had improved intracranial PFS and LTC. Moreover, WBRT + SIB also improved the long-term intracranial tumour control of small cell lung cancer patients. When evaluating toxicity, we found that WBRT + SIB might slightly increase the risk of radiation-induced brain injury, and that the risk increased with increasing dosage. However, low-dose WBRT + SIB had a tolerable radiation-induced brain injury risk, which was lower than that in the high-dose group, while it was comparable to that in the WBRT group.ConclusionsWBRT + SIB can be an efficient therapeutic option for patients with BMs, and is associated with improved intracranial LTC and PFS. Furthermore, low-dose WBRT + SIB (biologically effective dose [BED] ≤ 56 Gy) was recommended, based on the acceptable risk of radiation-induced brain injury and satisfactory tumour control.Trial registrationRetrospectively registered.

LMAP-04 CHOOSING WISELY BETWEEN RADIOTHERAPY DOSE-FRACTIONATION SCHEDULES: THE MOLECULAR GRADED PROGNOSTIC ASSESSMENT (MOLGPA) FOR ELDERLY GLIOBLASTOMA (EGBM-MOLGPA)

Abstract This study aimed develop a prognostic model integrating genomic characteristics in patients with elderly glioblastoma (eGBM), and compare the efficacy between conventionally fractionated radiotherapy (CFRT) vs. hypofractionated radiotherapy (HFRT). Patients aged ≥65 years who underwent radiotherapy for IDH-wildtype eGBM between 2006 and 2021 were included. Patients planned for a ≥6-week or ≤4-week radiotherapy were regarded as being treated with CFRT (334 patients; median, 60 Gy in 30 fractions) or HFRT (239 patients; median, 45 Gy in 15 fractions), respectively. We developed the molecular graded prognostic assessment score for eGBM (eGBM-molGPA) and assigned 0.0, 0.5, and 1.0 points in proportion to the corresponding hazard ratio (HR) of each prognostic factor for overall survival (OS). Temozolomide-based chemoradiation was applied for 86% of patients. With a median follow-up of 17.4 months, the median OS was 18.7 months for CFRT plus temozolomide group, 15.1 months for HFRT plus temozolomide group, and 10.4 months for RT alone group. The eGBM-molGPAwas established based on prognostic factors from multivariate analysis (performance, extent of resection, temozolomide, methylation of the MGMT promoter, subventricular zone involvement, temporalis muscle thickness, and the mutation status of TERT promoter and TP53 gene) and patients were allocated to three risk groups (high risk, total score 3.0–4.5; intermediate risk, 1.5–2.5; low risk, 0.0–1.0). Patients treated with CFRT plus temozolomide had significantly improved OS compared to those treated with HFRT plus temozolomide or radiotherapy alone in the low and intermediate risk groups (p&amp;lt;0.001). However, in the high-risk group, there was no significant difference in OS between treatment options. CFRT plus temozolomide can be a more effective strategy for selected eGBM patients compared to HFRT. For high-risk patients, a protracted treatment schedule might not be beneficial. The novel eGBM-molGPA can be used as a clinical tool for choosing wisely among radiotherapy options.

Estimating survival in patients with melanoma brain metastases: prognostic value of lactate dehydrogenase.

Patients with melanoma brain metastases (MBM) have poor prognosis, albeit advances in locoregional and systemic treatments. The melanoma-specific Graded Prognostic Assessment (GPA) effectively stratifies survival for patients with MBM. Nevertheless, lactate dehydrogenase (LDH), a well known prognostic factor for patients with melanoma, is not represented in the GPA scores and might add prognostic information for patients with MBM. In this study, 150 consecutive patients with MBM were retrospectively analyzed with the aim of evaluating independent prognostic factors for MBM patients, including LDH. Furthermore, we implemented a disease-specific prognostic score and estimated survival according to treatment modalities. On the basis of multivariable Cox regression analyses, six prognostic factors (age, BRAF status, number of MBM, number of extracranial metastatic sites, performance status, and LDH level) resulted statistically significant in terms of survival and were combined in a prognostic score to stratify patients in distinct prognostic groups ( P < 0.0001). Among treatment modalities, a multimodal approach with stereotactic radiosurgery or neurosurgery associated with systemic therapy showed the best outcome (median overall survival: 12.32 months, 95% confidence interval, 7.92-25.30). This is the first study to demonstrate that LDH has independent prognostic value for patients with MBM and might be used to improve prognostic stratification, albeit external validation is mandatory. Survival of patients with MBM is affected by both disease-specific risk factors and treatment modalities, with locoregional treatments associated with better outcomes.

Prevalence and Prognostic Significance of Malnutrition in Patients with Brain Metastasis.

Malnutrition is a severe but modifiable risk factor for cancers. However, the relationship between malnutrition and the survival of patients with brain metastases has not been fully revealed. We aimed to evaluate the prevalence of malnutrition and assess its prognostic value on patients with brain metastases. We retrospectively recruited 2,633 patients with brain metastases between January 2014 and September 2020. Three malnutrition scores were used to evaluate patients' malnutrition status at their first admission, including controlling nutritional status, the nutritional risk index, and the prognostic nutritional index. The association between malnutrition and overall survival (OS) was estimated. The three malnutrition scores were associated with each other and with body mass index (BMI). Malnutrition assessed by any of the three scores was significantly associated with poor OS. All three malnutrition scores were better indicators than BMI, and adding malnutrition scores to the Graded Prognostic Assessment (GPA) scoring system could significantly improve the accuracy of prognosis prediction. Malnutrition monitoring using any of the three malnutrition scores on patients' first admission could be a better survival indicator for patients with brain metastases compared with BMI alone. Malnutrition is a more significant indicator of survival stratification compared with BMI. Adding malnutrition to the GPA score system achieves better survival prediction.

Prognostic assessment in patients operated for brain metastasis from systemic tumors.

Established models for prognostic assessment in patients with brain metastasis do not stratify for prior surgery. Here we tested the prognostic accuracy of the Graded Prognostic Assessment (GPA) score model in patients operated for BM and explored further prognostic factors. We included 285 patients operated for brain metastasis at the University Hospital Zurich in the analysis. Information on patient characteristics, imaging, staging, peri- and postoperative complications and survival were extracted from the files and integrated into a multivariate Cox hazard model. The GPA score showed an association with outcome. We further identified residual tumor after surgery (p = 0.007, hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.1-2.3) steroid use (p = 0.021, HR 1.7, 95% CI 1.1-2.6) and number of extracranial metastasis sites (p = 0.009, HR 1.4, 95% CI 1.1-1.6) at the time of surgery as independent prognostic factors. A trend was observed for postoperative infection of the subarachnoid space (p = 0.102, HR 3.5, 95% CI 0.8-15.7). We confirm the prognostic capacity of the GPA score in a cohort of operated patients with brain metastasis. However, extent of resection and steroid use provide additional aid for the prognostic assessment in these patients.

Beyin Metastazlı İleri Evre KHDAK Hastalarında GPA İndeksinin Prognostik Değeri

Purpose: Graded Prognostic Assessment (GPA) is a new prognostic index for patients with brain metastases. Brain metastasis is a common site of metastasis in lung cancers. Lung cancer-specific GPA scoring system is used. We aimed to assess the prognostic and predictive significance of Graded Prognostic Assessment (GPA) score in non small-cell lung cancer patients with brain metastasis.&#x0D; Materials and Methods: This study was designed as a hospital-based retrospective observational case-series study. A total of 95 patients with brain metastatic NSCLC patients who were followed in two different oncology centers in Turkey between 2015 and 2021 have been included into this study. They were divided into 3 groups according to their GPA scores.&#x0D; Results: The median age of the patients was 62 (range 44-89) years The patients were divided into 3 groups according to their GPA scores. 24 (25.2 %) patients had ‘’0-1’’ GPA score, 54 (56,8 %) patients had ‘’1,5-2’’ GPA score and 17 (18 %) patients had ‘’2,5-3’’ GPA score. The median follow-up time was 11 months and 89 (93.7%) patients died during follow-up. Overall survival (OS) was 8 months. Patients in the low (0-1) GPA scores had worst overall survival than those with higher GPA scores (4.7, 12.6 and 18.5 months respectively and p=0,001).&#x0D; Conclusion: In this study, we have shown that GPA score is useful in evaluating the prognosis of NSCLC patients with brain metastasis

Optimal Treatment Strategy of Radiotherapy and Crizotinib for Patients with Brain Metastasis from ALK-Rearranged Non-Small-Cell Lung Cancer

<h3>Purpose/Objective(s)</h3> Radiotherapy and anaplastic lymphoma kinase (ALK) inhibitors are treatment options for brain metastasis (BM) in patients with ALK-rearranged non-small cell lung cancer (NSCLC). This study aimed to find the optimal treatment strategy for patients with BM from ALK-rearranged NSCLC. <h3>Materials/Methods</h3> Between 2012 and 2017, consecutive patients with BM from ALK-rearranged NSCLC treated with crizotinib and radiotherapy in our institution were reviewed and enrolled into the study. Patients were treated with sequential radiotherapy and crizotinib (upfront radiotherapy or crizotinib followed by the other at intracranial progression), or concurrent radiotherapy and crizotinib. The cumulative incidence of intracranial progression free survival (iPFS) and overall survival (OS) were estimated by the Kaplan-Meier method, and the log-rank test was used to analyze differences between the groups. A two-sided p value ≤ 0.05 were considered statistically significant. <h3>Results</h3> Totally 41 patients were enrolled, including 24 (58.5%) with sequential treatment and 17 (41.5%) with concurrent treatment. The diagnosis-specific graded prognostic assessment (DS-GPA) score was 0-2 in 25 (60.1%) patients and > 2 in 16 (39.0%) patients, respectively. There were 13(31.7%), 17 (41.5%), and 11 (26.8%) patients treated with stereotactic radiosurgery (SRS), whole brain radiotherapy (WBRT), and WBRT with simultaneous in-field boost (SIB), respectively. The median iPFS and OS in all patients were 33.5 (95% CI 30.8-36.2) months and 63.9 (95% CI 46.0-81.9) months, respectively. There was no significant difference of iPFS or OS between the sequential treatment group and the concurrent treatment group. However, in DS-GPA scores of 0-2, the iPFS was longer in the sequential treatment group than concurrent treatment group (67.9 months vs.32.6 months, <i>P</i>=0.045), but the difference of OS was not significant between the two groups (38.9 months vs. 32.6 months, <i>P</i>=0.829). Moreover, the median iPFS of patients receiving SRS, WBRT alone, and WBRT with SIB was 33.5 months, 43.6 months, and 63.9 months (P=0.047). The corresponding median OS was not reached, 26.0 months, and 67.9 months, respectively (<i>P</i><0.001). <h3>Conclusion</h3> For patients with BM from ALK-rearranged NSCLC in our study, sequential crizotinib and brain radiotherapy for patients with DS-GPA score of 0-2 achieve better iPFS. In addition, WBRT with SIB achieves the best iPFS.

NCOG-02. SURVIVAL AND TREATMENT OUTCOMES OF NEOPLASTIC MENINGITIS (NM)

Abstract INTRODUCTION NM occurs in 5 - 15% of cancer patients and Overall Survival (OS) in treated patients ranges from 2-6 months. The purpose of this study was to analyze the effect of prognostic factors on OS and calculate a graded prognostic assessment (GPA) score based on tissue type, similar to the index score created for cancer patients with brain metastases (BM). METHODS We conducted a single center, retrospective analysis of 118 patients diagnosed between 2006 and 2018 at TMC. The prognostic factors analyzed were: Age (&amp;lt; = 50yo =1pt), Karnofsky Performance Status (KPS &amp;gt; =60 =1 pt), and no extracranial metastases (1pt). The GPA score was calculated from 0.0 - 3.0 by adding the points together. Kaplan Meier curves were used to estimate OS for primary tumors with 10 or more patients (breast, lung, leukemia, lymphoma). Cox regression analysis was used to evaluate the association of the GPA with OS. RESULTS The GPA analysis by tumor type included 76% of the patient population. The median OS was 5 months (breast), 2 months (lung), 7 months (leukemia), and 2 months (lymphoma). We found that leukemia (p =0.008, N = 20) and lung cancer (p =0.002, N = 20) patients showed distinct separation between GPA groups on their Kaplan Meier curves. Higher KPS was associated with increased OS (p &amp;lt; 0.0001) using Cox regression. DISCUSSION: The GPA algorithm was only partially successful in our NM population, which may reflect the smaller number of patients in our study compared to the studies used to create the BM GPA. TMC is a contributing institution to a large, multi-institutional, multi-national registry of patients with NM disease (Neoplastic Meningitis Registry - NeMeRe). We plan to use this larger dataset to validate our GPA score as a useful tool for predicting OS in NM patients.

Prospective Neurocognitive Functions of Patients Treated With Concurrent Nivolumab and Stereotactic Brain Radiosurgery for NSCLC and RCC Brain Metastases

Previous studies have suggested activity of anti-PD1 antibodies against brain metastases from non-small cell lung cancer (NSCLC) and renal cell cancer (RCC). Our investigator-initiated phase 2 trial examined the neuropsychological effect of combining nivolumab with radiosurgery (SRS) in the treatment of patients with brain metastases from NSCLC and RCC.This is a multicenter open-label trial (NCT02978404) in which patients diagnosed with NSCLC or RCC, having ≤ 10 cc of un-irradiated brain metastases, no prior whole brain radiotherapy and no prior immunotherapy were eligible. Study treatment commenced with a dose of nivolumab (240mg or 480mg IV), which was continued until progression for up to 2 years at bi-weekly or monthly intervals. SRS (15-21 Gy) to all visible un-irradiated brain lesions was administered within 14 days of the first dose of nivolumab (cycle 1). Patients were followed by brain MRI and CT scans of the chest, abdomen and pelvis. Neurocognitive assessment was performed using the Hopkins verbal learning test-revised (HVLT-R), the Trail Making Test (TMT) and the Controlled Oral Word Association Test (COWA) RESULTS: 26 study patients (22 NSCLC and 4 RCC) were enrolled between Aug 2017 and January 2020. Patients had a median of 2 (1-9) brain metastases treated with SRS. The median diagnosis-specific graded prognostic assessment (GPA) score was 2 (1-3). Forty-two percent of the patients had received prior cytotoxic chemotherapy, and 1 patient had received prior brain SRS. PD-L1 status was known for 21 of the 22 NSCLC patients (12 with ≥50% PD-L1 expression (DAKO 22C3)). Median icPFS was 5.0 months (6 intracranial progressions and 9 deaths without progression in the brain). Accounting for death as a competing risk, the 1-year cumulative incidence of intracranial relapse was 20%, whereas the rate of extracranial relapse was 48.3% at 1-year. Median overall survival was 14 months. Neuropsychological evaluation was completed in 16 and 9 patients at 3 and 6-month follow-up, respectively. Median age of the 16 patients was 63 (46-77). At 3 months follow up, there was no significant difference on the patient's mean performance in any of the neurocognitive assessments; a deterioration of ≥1 standard deviation in at least 1 assessment from baseline was observed in 8 (50%) patients. At 6 months, participants significantly improved on the TMT- Parts A (P = 0.04) and Parts B (P = 0.03).Neurocognitive assessments suggest that upfront SRS concurrent with nivolumab PD1 inhibition is safe. Patient neurocognitive function showed potential improvements in patients able to complete 6-month assessments. A potential synergy between nivolumab and SRS loco-regionally within the brain may be present, leading to high intracranial control. However, the high rate of extracranial progression does not suggest an abscopal effect triggered by SRS during nivolumab.G.L. Masucci: Research Grant; BMS.O. Boucher: None. F. Marie: None. M. Plourde: None. V. Panet-Raymond: None. M. Pavic: None. S. Owen: None. L. Masson-Cote: None. C. Menard: Research Grant; Siemens Healthcare, Philips, Progenics, Varian. B. Routy: None. M. Tehfe: None. N. Blais: consultant; BMS.D. Roberge: Independent Contractor; CHUM, CDL Proton Therapy. Research Grant; Elekta. Honoraria; BrainLab, Varian Medical Systems, Siemens Medical Systems, EMD Serono, recordati. In-kind Donation; Accuray. ownership stake; afx, croton healthcare. P. Wong: Research Grant; BMS, AstraZeneca, NexPlasmaGen. Advisory Board; BMS, AstraZeneca. Travel Expenses; BMS, AstraZeneca.

Estimating survival and clinical outcome in advanced non-small cell lung cancer with bone-only metastasis using molecular markers

ObjectivesThis retrospective study investigated prognostic factors in advanced non-small cell lung cancer (NSCLC) with bone-only metastasis, and developed a graded prognostic assessment (GPA) model to estimate patient survival. MethodsThe primary endpoint was overall survival. We investigated the patients with advanced NSCLC with bone-only metastasis at the initial diagnosis and diagnosed between 2013 and 2019 in our hospital. A log-rank test and Cox proportional hazards model were used to examine factors. A GPA model was developed in the training set based on the factors that were determined significant according to their hazard ratios and verified by the validation set. ResultsWe finally included 220 patients for analysis. These patients were divided into two groups, 147 cases for the training cohort and 73 for the validation cohort. The following were significant independent prognostic factors, and were included in the GPA model: smoking; EGFR (epidermal growth factor receptor) sensitive/ALK (anaplastic lymphoma kinase) mutations; loss of weight; hypoalbuminemia; and primary site treated by surgery or radiotherapy. GPA score of nil was assigned to smoking, without sensitive mutations, loss of weight, hypoalbuminemia, and without local treatment of primary site; the corresponding superior alternatives were scored 1.5, 2.0, 1.5, 1.5, and 1.5, respectively. The median survival times of patients with GPA scores of nil to 3.0, 3.5 to 6.0, and 6.5 to 8.0 were 14.2, 29.5, and 56.6 months in the training set (P < 0.001) and 15.2, 31.2, and 54.0 months in the validation set (P < 0.001). ConclusionThe survival time of patients with NSCLC with bone-only metastasis was dramatically influenced by the presence of the determined prognostic factors. The GPA model developed in this study may be a useful clinical tool to estimate the life expectancy of these patients, and guide treatment.

The Presence of Genomic Instability in Cerebrospinal Fluid in Patients with Meningeal Metastasis

PurposeThis study aimed to explore the genomic instability in cerebrospinal fluid (CSF) in patients with meningeal metastasis (MM).Material and MethodsWe collected the blood and CSF samples of 15 MM patients and one brain parenchymal metastasis (BPM) patient. A panel of 543 cancer-related genes was conducted to analyze the status of genomic instability in CSF and plasma cell-free DNA (cfDNA) of all patients. Subsequently, nine patients underwent low-depth whole-genome sequencing (WGS) analysis to verify the existence of genomic instability, followed by genomic scoring by the application of aneuploidy scores. Diagnosis-specific graded prognostic assessment (DS-GPA) score was utilized to assess the clinical status of MM patients.ResultsThere was significant difference in gene mutation between CSF cfDNA and plasma cfDNA in MM patients. Among them, 12 MM patients developed genomic instability in their CSF cfDNA, while the remaining 3 had stable genetic profile. Besides, BPM patients showed genomic stability in his CSF and paraffin-embedded tissue sections. No genomic instability was noticed in plasma cfDNA of all patients. Sensitive mutations on EGFR, ERBB2, ALK and KRAS genes and increased gene copy numbers of MET and ERBB2 were detected in 10 MM patients with genomic instability, as well as the EGFR gene mutation in one MM case with genomic stability. Additionally, MM patients with genomic instability had lower overall survival and higher aneuploidy scores and tumor mutation burden compared with those with genomic stability. Moreover, MM patients with higher DS-GPA scores benefited from better survival.ConclusionGenomic instability existed in the CSF cfDNA rather than plasma cfDNA of MM patients, which might be the underlying cause of the differences in MM.

Surgery for brain metastases – real-world prognostic factors’ association with survival

Background Surgical resection of brain metastases (BM) improves overall survival (OS) in selected patients. Selecting those patients likely to benefit from surgery is challenging. The Graded Prognostic Assessment (GPA) and the diagnosis-specific Graded Prognostic Assessment (ds-GPA) were developed to predict survival in patients with BM, but not specifically to guide patient selection for surgery. Our aim was to evaluate the feasibility of preoperative GPA/ds-GPA scores and assess variables associated with OS. Methods We retrospectively reviewed first-time surgical resection of BM from solid tumors at a Norwegian regional referral center from 2011 to 2018. Results Of 590 patients, 51% were female and median age was 63 years. Median OS was 10.3 months and 74 patients (13%) died within three months after surgery. Preoperatively tumor origin was unknown in 20% of patients. A GPA score could be calculated for 92% of the patients preoperatively, but could not correctly predict survival. A ds-GPA score could be calculated for 46% of patients. Multivariable regression analysis revealed shorter OS in patients with higher age, worse functioning status, colorectal primary cancer compared to lung cancer, presence of extracranial metastases, and more than four BM. Patients with preoperative progressive extracranial disease or synchronous BM had shorter OS compared to patients with stable extracranial disease. Conclusion Ds-GPA could be calculated in less than half of patients preoperatively and GPA poorly identified patients which had minimal benefit of surgery. Including status of extracranial disease improve prognostication and therefore selection to surgery for brain metastases.

Brain Metastases from Esophageal Squamous Cell Carcinoma: Clinical Characteristics and Prognosis.

PurposeDue to the low incidence of intracranial disease among patients with esophageal cancer (EC), optimal management for these patients has not been established. The aim of this real-world study is to describe the clinical characteristics, treatment approaches, and outcomes for esophageal squamous cell carcinoma (ESCC) patients with brain metastases in order to provide a reference for treatment and associated outcomes of these patients.MethodsPatients with ESCC treated at the Fourth Hospital of Hebei Medical University between January 1, 2009 and May 31,2020 were identified in an institutional tumor registry. Patients with brain metastases were included for further analysis and categorized by treatment received. Survival was evaluated by the Kaplan-Meier method and Cox proportional hazards models.ResultsAmong 19,225 patients with ESCC, 66 (0.34%) were diagnosed with brain metastases. Five patients were treated with surgery, 40 patients were treated with radiotherapy, 10 with systemic therapy alone, and 15 with supportive care alone. The median follow-up time was 7.3 months (95% CI 7.4-11.4). At last follow-up, 59 patients are deceased and 7 patients are alive. Median overall survival (OS) from time of brain metastases diagnosis was 7.6 months (95% CI 5.3-9.9) for all cases. For patients who received locoregional treatment, median OS was 10.9 months (95% CI 7.4-14.3), and survival rates at 6 and 12 months were 75.6% and 37.2%, respectively. For patients without locoregional treatment, median OS was 3.0 months (95% CI 2.5-3.5), and survival rates at 6 and 12 months were 32% and 24%, respectively. OS was significantly improved for patients who received locoregional treatment compared to those treated with systematic treatment alone or supportive care (HR: 2.761, 95% CI 1.509-5.053, P=0.001). The median OS of patients with graded prognostic assessment (GPA) score 0-2 was 6.4 months, compared to median OS of 12.3 months for patients with GPA >2 (HR: 0.507, 95% CI 0.283-0.911).ConclusionBrain metastases are rare in patients with ESCC. GPA score maybe a useful prognostic tool for ESCC patients with brain metastases. Receipt of locoregional treatment including brain surgery and radiotherapy was associated with improved survival.

The individual risk of symptomatic radionecrosis after brain metastasis radiosurgery is predicted by a continuous function of the V12Gy

IntroductionBrain metastases are frequently treated with stereotactic radiosurgery (SRS). Radionecrosis (RN) is the late side effect in up to 24% of patients, being symptomatic in 8–10%. Fixed values of the radiosurgical volume receiving 12 Gy or more (V12Gy) are used to roughly predict the global risk. The aim of this retrospective study is to fine-tune the model of individual risk prediction for symptomatic radionecrosis and identify modulating factors. Materials and methodsData of patients treated with SRS for ≤3 BM of solid tumours at CHU-UCL-Namur were retrospectively reviewed. Doses ranging from 15 to 24 Gy were prescribed to the 70% isodose in function of the lesion diameter. Treatment was administered with a stereotactic linear accelerator. Follow-up magnetic resonance imaging was performed 3-monthly for 18 months and 6-monthly thereafter. RN was prospectively diagnosed and confirmed by the tumour board. V12Gy, previous or salvage whole-brain radiotherapy (WBRT), smoking history, diabetes, postoperative SRS, diagnosis-specific graded prognostic assessment score, cerebral lobe location and relative location (superficial versus deep) were retrieved. Univariate and multivariate analyses were performed to assess their predictive values and derive a model. Results128 patients with 220 lesions were analysed. The risk of RN was predicted by a continuous function of the V12Gy (p = 0.005). No other factor had a significant impact, particularly WBRT that did not increase the risk. ConclusionThe risk of symptomatic RN is predicted on an individual basis by a model in function of the V12Gy and must be confirmed in a prospective study.

Evaluation of Prognostic Factors that Affect Survival Outcomes of Breast Cancer Patients with Brain Metastases: A Single Institutional Experience.

This study aimed to evaluate various prognostic factors that play a vital role in stratifying and guiding tailored treatment strategies and survival outcome in breast cancer patients with brain metastases (BM). Data regarding demography, clinical presentation, molecular subtypes, risk-stratification, treatment details, and outcomes were retrieved from medical records. All time-to-event (survival) outcomes were analyzed by Kaplan-Meir method and compared using log-rank test. Univariate and multivariate analysis of relevant prognostic factors were performed and p-values ≤0.05 were considered statistically significant. A total of 88 patients (median age: 50 years) were included for this study. The median follow-up time of all surviving patients was ~20 months. During the follow-up, 82 (93.1%) patients died. The median survival of all patients was 12 months, with 1-year and 2-year overall survival (OS) rate of 51% and 22%, respectively. Based on univariate analysis, statistically significant prognostic factors for OS were molecular subtypes, number of BM, and Karnofsky Performance Status (KPS); however, number of BM and KPS emerged as independent predictors of survival based on multivariate analysis. We conclude that, there are other important prognostic factor, such as number of BM, which may affect the OS of these patients, in addition to variables included in the diagnosis-specific graded prognostic assessment score. Prospective studies evaluating these factors are necessary to further refine the stratification of patients, which will aid the initiation of appropriate treatment to improve the OS of patients.

Long-term Survival with 18-Fluorodeoxyglucose Positron Emission Tomography-directed Therapy in Non-small Cell Lung Cancer with Synchronous Solitary Brain Metastasis

AimsAt diagnosis, <1% of patients with non-small cell lung cancer (NSCLC) have synchronous solitary brain metastasis (SSBM). In prior cohorts without 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) staging, definitive treatment to intracranial and intrathoracic disease showed a 5-year overall survival (OS) of 11–21%. We investigated the long-term survival outcomes for patients with SSBM NSCLC, diagnosed in the FDG-PET/CT era and treated definitively with local therapies to both intracranial and intrathoracic sites of disease. Materials and methodsThis retrospective study assessed patients staged with FDG-PET/CT who received definitive lung and SSBM treatment from February 1999 to December 2017. A lung-molecular graded prognostic assessment (lung-molGPA) score was assigned for each patient using age, performance status score, and, where carried out, molecular status. Overall survival and progression-free survival (PFS) were calculated using Kaplan–Meier methods. Cox proportional hazard models determined OS and PFS prognostic factors. ResultsForty-nine patients newly diagnosed with NSCLC and SSBM had a median age of 63 years (range 34–76). The median follow-up of all patients was 3.9 years. Thirty-three patients (67%) had ≥T2 disease, 23 (47%) had ≥N2. At 2 years, 45% of first failures were intracranial only (95% confidence interval 30–59). At 3 and 5 years, OS was 45% (95% confidence interval 32–63) and 30% (95% confidence interval 18–51), respectively. In ≥N1 disease, 5-year OS was 34% (95% confidence interval 18–63). The 3- and 5-year PFS was 8% (95% confidence interval 3–22) and 0%, respectively. Higher lung-molGPA was associated with longer OS (hazard ratio 0.26, 95% confidence interval 0.11–0.61, P = 0.002). Higher lung-molGPA (hazard ratio 0.33, 95% confidence interval 0.15–0.71, P = 0.005) and lower N-stage (hazard ratio 1.56, 95% confidence interval 1.13–2.15, P = 0.007) were associated with longer PFS. ConclusionsDefinitive treatment of patients with NSCLC and SSBM staged with FDG-PET/CT can result in 5-year survivors, including those with ≥N1 disease.

Surgical outcome and graded prognostic assessment of patients with brain metastasis from adult sarcoma: multi-institutional retrospective study in Japan.

Brain metastasis (BM) is an uncommon complication of sarcomas with a poor prognosis. Little information is available about the feasibility and prognostic factors of surgical resection of BM from sarcomas. This study involved a retrospective analysis of 22 patients with BM from sarcomas who underwent resection at six institutes in Japan. Prognostic factors were analyzed to develop a graded prognostic assessment (GPA) using the log-rank test and Cox regression analysis. For validation of this GPA, we collected data on 100 surgical cases from 48 published reports. Postoperative Karnofsky Performance Status (KPS) improved in 50% of our patients. Median overall survival (OS) was 21months. Multivariate analysis showed age and alveolar soft part sarcoma (ASPS) were significant preoperative prognostic factors (P < 0.05). RTOG-RPA classification had no significant prognostic value. We developed a GPA system for OS after resection of BM. A score of 0 was assigned to patients aged 18-29years with non-ASPS, 2 to patients aged 18-29years with ASPS or 30-76years with non-ASPS, and 4 to patients aged 30-76years with ASPS. Median OS for patients with GPA scores of 0, 2, and 4 were 6.5, 16.0, and 44.0months, respectively (P = 0.002). The results were validated by the data of 100 cases compiled (P < 0.001). Median OS of patients with BM from sarcomas was comparable to that from carcinomas after resection. A new sarcoma-specific GPA may help patients and clinicians to select resection as an option for treatment of BM from sarcomas.