Disease-specific Graded Prognostic Assessment Research Articles

Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI): One-Year Safety and Efficacy Outcomes from a Multicenter Phase I Trial

The combination of immunotherapy and single-fraction stereotactic radiosurgery (SRS) for treatment of metastatic brain disease has yielded symptomatic radiation necrosis rates as high as 20% (PMID: 29327059). Consequently, the Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI) multicenter phase I trial (registered at clinicaltrials.gov, NCT04047602) was created to address whether reduced-dose SRS can improve morbidity without compromising efficacy. In this report we present our one-year findings. Eligibility for RADREMI enrollment required brain metastases patients with: a) Histologically-confirmed primary malignancy, b) Receipt of immunotherapy within 30 days of SRS, c) 1-10 MRI-visible brain metastases, d) Estimated median survival of at least 6 months (via disease-specific graded prognostic assessment), and e) No history of whole brain radiation therapy. Reduced-dose SRS utilized 18 Gy for lesions 0-2 cm, 14 Gy for lesions 2.1-3 cm, and 12 Gy for lesions 3.1-4 cm. Symptomatic radiation necrosis was defined as imaging findings consistent with radiation necrosis combined with clinical symptoms requiring steroid administration and/or operative intervention. Local control was defined by Response Assessment in Neuro-Oncology (RANO) criteria. From December 18, 2019 to June 30, 2022, 54 lesions in 17 patients were treated on RADREMI with at least one-year of follow-up. One-year local control occurred in 52 of 54 lesions and in 15 of 17 patients, yielding control rates of 96% per lesion and 88% per patient. Radiographic radiation necrosis occurred in 2 of 54 lesions (4%). No symptomatic radiation necrosis occurred. Our findings of concurrent immunotherapy + reduced-dose SRS at one-year post-treatment revealed excellent local control (96%) with no symptomatic radiation necrosis, and minimal radiographic radiation necrosis. These results attest to the durability of the safety and efficacy of reduced-dose SRS with immunotherapy for metastatic brain disease.

Radiosurgery dose reduction for brain metastases on immunotherapy (RADREMI): Results of an a priori interim analysis of a multicenter phase I trial.

2013 Background: Symptomatic radiation necrosis rates in patients treated with immune checkpoint inhibitor (ICI) therapy and concomitant single-fraction stereotactic radiosurgery (SRS) are as high as 20% (PMID: 29327059). We present updated results from the Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI) trial following completion of an a priori interim analysis, aimed to identify reduced-dose SRS that is safe and efficacious for this patient population. Methods: RADREMI (clinicaltrials.gov, NCT04047602) is a prospective multicenter single arm Phase I trial involving patients age > 18 receiving ICI with SRS for 1-10 brain metastases on MRI. Patients had biopsy-confirmed primary malignancy with disease-specific graded prognostic assessment estimated median survival of at least 6 months and no previous whole brain radiation therapy. Six-month symptomatic radiation necrosis (radiographic radiation necrosis + clinical symptoms requiring steroid administration and/or operative intervention) was the primary endpoint, based on an expected rate of 5% and a historical rate of 16%. Secondary endpoints included 6-month local control and radiographic radiation necrosis. Response Assessment in Neuro-Oncology criteria defined local control; findings were compared to historical 6-month local control of 87-91% with RTOG 90-05 SRS dosing. A pre-determined interim futility analysis (based on the null hypothesis of no fewer than 15 of the first 20 patients reaching the primary endpoint achieving 6-month local control for RADREMI dosing) was performed using the Fisher’s exact test. Results: Between December 18, 2019 and September 10, 2021, 43 lesions were treated in 16 patients receiving ICI delivered within 30 days before SRS who were enrolled on trial and met the primary endpoint (median follow-up = 9.1 months). All patients received RADREMI SRS dosing (18 Gy for lesions 0-2 cm, 14 Gy for lesions 2.1-3 cm, and 12 Gy for lesions 3.1-4 cm). The most common ICI used was single-agent pembrolizumab (51% of lesions, 56% of patients), followed by single-agent nivolumab (28% of lesions, 13% of patients). The six-month rates of symptomatic and radiographic radiation necrosis were zero; the six-month local control rate was 98% per treated lesion (42/43), and 94% per treated patient (15/16), comparable to historical controls (p > 0.05) and sufficient to not reject the interim futility analysis null hypothesis. Conclusions: Interim analysis reveals that the safety and efficacy of RADREMI dosing for reducing SRS dose in brain metastasis patients receiving concomitant ICI persists with excellent local control and no morbidity in a multi-institutional collaborative trial. Further results following completion of trial enrollment will provide additional evidence regarding the safety and efficacy of RADREMI SRS dosing. Clinical trial information: NCT04047602.

Radiosurgery dose reduction for brain metastases on immunotherapy (RADREMI): Early results from a multicenter phase I trial.

2025 Background: The rate of symptomatic radiation necrosis in patients treated with immune checkpoint inhibitor (ICI) therapy and concomitant single-fraction stereotactic radiosurgery (SRS) is as high as 20% (Martin et al., JAMA Oncology 2018). Here, we present the first results from the Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI) trial, aimed to identify reduced-dose SRS that is safe and efficacious for this patient population. Methods: RADREMI is a prospective multicenter, single arm phase I pilot study. Patients age > 18 receiving ICI with SRS for 1-10 brain metastases on MRI from biopsy-confirmed primary malignancy with estimated median survival of at least 6 months (by disease-specific graded prognostic assessment) and no history of whole brain radiation therapy were eligible. The primary endpoint was six-month symptomatic radiation necrosis (defined as a six-month rate of clinical symptomatology requiring steroid administration and/or operative intervention concomitant with imaging findings consistent with radiation necrosis), based on a historical six-month symptomatic radiation necrosis rate of 16% and an expected rate of 5%. Secondary endpoints included six-month local control and six-month radiographic radiation necrosis. Local control was defined according to Response Assessment in Neuro-Oncology (RANO) criteria, and was compared to historical controls of 87-91% six-month local control with RTOG 90-05 SRS dosing. The Fisher’s exact test was used for statistical analysis. This trial is registered at clinicaltrials.gov, NCT04047602. Results: Between December 18, 2019 and January 21, 2021, 39 lesions were treated in 17 patients receiving ICI delivered within 30 days before SRS from whom we recruited and obtained consent. All patients were treated with RADREMI dosing, which involved SRS doses of 18 Gy for lesions 0-2 cm, 14 Gy for lesions 2.1-3 cm, and 12 Gy for lesions 3.1-4 cm. The most common ICI used was single-agent pembrolizumab (49% of lesions, 59% of patients), followed by single-agent nivolumab (31% of lesions, 12% of patients). For the 11 lesions (six patients) meeting the primary endpoint (median follow-up = 259 days), the six-month symptomatic radiation necrosis rate was 0% per treated lesion, and 0% per treated patient, which was not significantly different from historical controls (p = 0.478). The six-month local control rate was 100% per treated lesion, and 100% per treated patient, comparable to historical controls (p = 0.476). Conclusions: In the first prospective trial to investigate dose-reduced SRS with concomitant ICI in treating metastatic brain disease, early results support the safety and efficacy of RADREMI dosing in this patient population. These findings warrant further multi-institutional collaborative trials of RADREMI dosing for this population. Clinical trial information: NCT04047602.

Prognostic factors of colorectal cancer patients with brain metastases

IntroductionBrain metastases (BMs) from colorectal cancer (CRC) are rare (≈2%) but are increasing with the improvement of CRC prognosis. The main objective of this study was to evaluate the prognostic factors of BM from CRC. Materials and methodsThis multicenter retrospective study included all consecutive patients with BM from CRC diagnosed between 2000 and 2017. Theory/calculationPrognostic factors of OS were evaluated in univariate (log-rank test) and multivariate analyses (Cox regression model). These prognostic factors could help the management of patients with BM from CRC. ResultsA total of 358 patients were included with a median age of 65.5 years. Primary tumors were mostly located in the rectum (42.4%) or left colon (37.2%) and frequently KRAS-mutated (56.9%). The median time from metastatic CRC diagnosis to BM diagnosis was 18.5 ± 2.5 months. BMs were predominantly single (56.9%) and only supratentorial (54.4%). BM resection was performed in 33.0% of the cases and 73.2% of patients had brain radiotherapy alone or after surgery. Median OS was 5.1 ± 0.3 months. In multivariate analysis, age under 65 years, ECOG performance status 0–1, single BM and less than 3 chemotherapy lines before BM diagnosis were associated with better OS. Prognostic scores, i.e. recursive partitioning analysis (RPA), Graded Prognostic Assessment (GPA), Disease Specific-Graded Prognostic Assessment (DS-GPA), Gastro-Intestinal-Graded Prognostic Assessment (GI-GPA) and the nomogram were statistically significantly associated with OS but the most relevant prognosis criteria seemed the ECOG performance status 0–1. ConclusionsECOG performance status, number of BM and number of chemotherapy lines are the most relevant factors in the management of patients with BM from CRC.

An integrated disease-specific graded prognostic assessment scale for melanoma: contributions of KPS, CITV, number of metastases, and BRAF mutation status.

BackgroundStereotactic radiosurgery (SRS) remains a mainstay therapy in the treatment of melanoma brain metastases (BM). While prognostic scales have been developed for melanoma patients who underwent SRS treatment for BM, the pertinence of these scales in the context of molecularly targeted therapies remains unclear.MethodsThrough a multi-institutional collaboration, we collated the survival patterns of 331 melanoma BM patients with known BRAF mutation status treated with SRS. We established a prognostic scale that was validated in an independent cohort of 174 patients. All patients with BRAF mutations in this series were treated with BRAF inhibitors. Prognostic utility was assessed using Net Reclassification Index (NRI > 0) and integrated discrimination improvement (IDI) metrics.ResultsIn a multivariate Cox proportional hazards model, BRAF mutation status, KPS, number of metastases, and cumulative intracranial tumor volume (CITV) independently contributed to survival prognostication for melanoma patients with SRS-treated BM (P < .05 for all variables). These variables were incorporated into a prognostic scale using the disease-specific graded prognostic assessment (ds-GPA) framework. This integrated melanoma ds-GPA scale was validated in 2 independent cohorts collated through a multi-institutional collaboration. In terms of order of prognostic importance, BRAF mutation status exerted the greatest influence on survival, while KPS, the number of metastases, and CITV exhibited comparable, lesser impacts.ConclusionsOptimal survival prognostication for SRS-treated patients with melanoma BM requires an integrated assessment of patient characteristics (KPS), tumor characteristics (CITV and number of metastases), and the mutational profile of the melanoma (BRAF mutation status).

Brain metastases from primary colorectal cancer: is radiosurgery an effective treatment approach? Results of a multicenter study of the radiation and clinical oncology Italian association (AIRO).

The prognosis of brain metastatic colorectal cancer patients (BMCRC) is poor. Several local treatments have been used, but the optimal treatment choice remains an unresolved issue. We evaluated the clinical outcomes of a large series of BMCRC patients treated in several Italian centers using stereotactic radiosurgery (SRS). 185 BMCRC patients for a total of 262 lesions treated were evaluated. Treatments included surgery followed by post-operative SRS to the resection cavity, and SRS, either single-fraction, then hypofractionated SRS (HSRS). Outcomes was measured in terms of local control (LC), toxicities, brain distant failure (BDF), and overall survival (OS). Prognostic factors influencing survival were assed too. The median follow-up time was 33 months (range 3-183 months). Surgery plus SRS have been performed in 28 (10.7%) cases, SRS in 141 (53.8%), and HSRS in 93 (35.5%). 77 (41.6%) patients received systemic therapy. The main total dose and fractionation used were 24 Gy in single fraction or 24 Gy in three daily fractions. Local recurrence occurred in 32 (17.3%) patients. Median, 6 months,1-year-LC were 86 months (95%CI 36-86), 87.2% ± 2.8, 77.8% ± 4.1. Median,6 months,1-year-BDF were 23 months (95%CI 9-44), 66.4% ± 3.9, 55.3% ± 4.5. Median,6 months,1-year-OS were 7 months (95% CI 6-9), 52.7% ± 3.6, 33% ± 3.5. No severe neurological toxicity occurred. Stage at diagnosis, Karnofsky Performance Status (KPS), presence and number of extracranial metastases, and disease-specific-graded-prognostic-assessment (DS-GPA) score were observed as conditioning survival. SRS/HSRS have proven to be an effective local treatment for BMCRC. A careful evaluation of prognostic factors as well as a multidisciplinary evaluation is a valid aid to manage the optimal therapeutic strategy for CTC patients with BMs. The prognosis of BMCRC is poor. Several local treatments was used, but optimal treatment choice remains undefined. Radiosurgery has proven to be an effective local treatment for BMCRC. A careful evaluation of prognostic factors and a multidisciplinary evaluation needed.

ALK-Brain Prognostic Index-Preliminary Study of a Prognostic Tool for Patients with ALK-Rearranged, Non-small Cell Lung Cancer and Brain Metastases.

Background: Disease-specific Graded Prognostic Assessment (DS-GPA) is the most validated prognostic tool for patients with brain metastasized lung cancer. The Lung-molGPA scoring system was recently introduced for oncogenic-driven brain metastasized lung cancer, but has not yet been validated in cohorts including only ALK-translocated tumors. Methods: We designed a retrospective cohort study consisting of 44 patients with brain metastasized ALK-positive, non-small cell lung cancer (NSCLC) who were treated between January 2009 and November 2019 at Karolinska University Hospital in Stockholm, Sweden. Information about demographics and clinicopathological parameters were collected. Predictors of overall survival (OS) were identified by Cox regression analyses. A bootstrap validation with 1000 samples was performed in order to compare the different prognostic scores. Results: The variables found to independently influence OS in the multivariate analysis, i.e., PS, sex and brain metastases at diagnosis, were used as prognostic variables in our new prognostic index (ALK-BPI). Patients were divided into two prognostic groups. The median OS was 65.7 months for the good prognostic group and 22.7 months for the poor prognostic group (p = 0.0068). In the univariate analysis of the different prognostic scores, ALK-BPI performed better than the others (HR = 3.6; 95% CI: 1.3–9.9). The mean C-statistics of the different prognostic scores were compared to each other, and no significant difference was observed. Conclusion: We propose the ALK-BPI score as a new prognostic tool that can easily be applied for ALK-positive lung cancer patients with brain metastases in daily clinical practice, as it has at least the same prognostic value as Lung-molGPA.

Development of a disease-specific graded prognostic assessment index for the management of sarcoma patients with brain metastases (Sarcoma-GPA)

BackgroundBrain metastases from sarcomatous lesions pose a management challenge owing to their rarity and the histopathological heterogeneity. Prognostic indices such as the Graded Prognostic Assessment (GPA) index have been developed for several primary tumour types presenting with brain metastases (e.g. lung, breast, melanoma), tailored to the specifics of different primary histologies and molecular profiles. Thus far, a prognostic index to direct treatment decisions is lacking for adult sarcoma patients with brain metastases.MethodsWe performed a multicentre analysis of a national group of expert sarcoma tertiary centres (French Sarcoma Group, GSF-GETO) with the participation of one Canadian and one Swiss centre. The study cohort included adult patients with a diagnosis of a bone or soft tissue sarcoma presenting parenchymal or meningeal brain metastases, managed between January 1992 and March 2012. We assessed the validity of the original GPA index in this patient population and developed a disease-specific Sarcoma-GPA index.ResultsThe original GPA index is not prognostic for sarcoma brain metastasis patients. We have developed a dedicated Sarcoma-GPA index that identifies a sub-group of patients with particularly favourable prognosis based on histology, number of brain lesions and performance status.ConclusionsThe Sarcoma-GPA index provides a novel tool for sarcoma oncologists to guide clinical decision-making and outcomes research.

1579P - Prognostic factors for non-small cell lung cancer patients with driver mutation negative and brain metastases (HOT 1701)

BackgroundNon-small cell lung cancer (NSCLC) is characterized by a high incidence of brain metastasis (BM) and the prognosis of NSCLC patients with BM is poor. Previous study demonstrated four prognostic factors, which were age, poor PS, presence of extracranial metastases (ECM), and number of BM, in NSCLC patients with BM. This study aimed to identify prognostic factors and clarify the survival in NSCLC patients with BM at the time of a diagnosis. MethodsA total of 566 NSCLC patients with BM from 15 institutions between January 2008 and December 2014. Among them, 176 patients had driver mutation, such as EGFR mutation and ALK-rearrangement, and 390 patients did not. This retrospective study focused on the 390 NSCLC patients without driver mutation, and identified clinical prognostic factors using Cox proportional hazards model. Moreover, we validated the disease specific Graded prognostic assessment (DS-GPA) in this cohort. ResultsMedian OS was 7.6 months, respectively (95% confidence interval [CI]; 6.5-8.7, data cut-off; December 2018). Multivariate analyses demonstrated the following independent prognostic factors; gender male (P=0.001), age > 64 years (P=0.009), poor PS (P<0.001), T factor (P=0.001), N factor (P=0.028), histological type of non-adenocarcinoma (P<0.001), presence of ECM (P<0.001), and number of BM (P=0.023). The median survival of four patient groups according to DS-GPA demonstrated 4.1 (GPA 0-1.0, n=146, 95% CI, 3.2-5.1), 8.3 (GPA 1.5-2.0, n=136, 95% CI, 6.5-10.1), 12.5 (GPA 2.5-3.0, n=96, 95% CI, 9.3-15.7), 21.4 (GPA 3.5-4.0, n=12, 95% CI, 0-43.2) months, respectively. ConclusionsPrognosis of NSCLC patients with EGFR, ALK negative and BM is poor. In addition to the known prognostic factors such as DS-GPA, this study shown that male, T factor, N factor, and histological type of non-adenocarcinoma, had a prognostic role in NSCLC patients with driver mutation negative and BM. Clinical trial identificationUMIN000030313, 08/12/2017. Legal entity responsible for the studyHokkaido Lung Cancer Clinical Study Group Trial: HOT. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

131P - Upfront whole brain radiotherapy for multiple brain metastases in patients with EGFR-mutant lung adenocarcinoma

Purpose: This study aimed to evaluate the efficacy of upfront whole-brain radiotherapy (WBRT) in EGFR-mutant lung adenocarcinoma patients with multiple brain metastases (BM). Methods: In this study, 195 patients with EGFR mutations who had multiple BM at preliminary diagnosis were included and retrospectively reviewed. Patients were admitted to receive the following treatments in a multi-disciplinary setting: upfront WBRT followed by EGFR-TKI, concurrent EGFR-TKI and WBRT and upfront EGFR-TKI followed by WBRT. A disease-specific graded prognostic assessment (DS-GPA) was performed for all the patients. The treatment response and overall survival (OS) were assessed as well. Results: The median OS of these patients was 27 months. Objective response rate (ORR) was significantly better in upfront WBRT group than other two groups (P=0.004). Moreover, patients who received upfront WBRT (n=67) had longer OS than the concomitant group (36 vs 25 months; P=0.006) and the upfront EGFR-TKI group (36 vs 25 months; P<0.0001). The prognosis of patients with different DS-GPA scores significantly differed (P<0.0001). In concomitant group and upfront EGFR-TKIs group, patients with higher DS-GPA scores of 2-3 had more favorable prognosis compared with those with lower DS-GPA scores of 0-1.5 (27 vs 25 months; P=0.023). Patients who received EGFR-TKIs concurrently with WBRT had longer OS than those received upfront EGFR-TKIs with high DS-GPA scores. (37 vs 17 months; P=0.023). Conclusion: The use of upfront WBRT for EGFR-mutated lung adenocarcinoma patients with multiple BM can improve ORR and OS. More importantly, patients with high DS-GPA scores are recommended to receive WBRT immediately after EGFR-TKIs therapy.

Upfront whole brain radiotherapy for multiple brain metastases in patients with EGFR-mutant lung adenocarcinoma.

Purpose: This study aimed to evaluate the efficacy of upfront whole-brain radiotherapy (WBRT) in EGFR-mutant lung adenocarcinoma patients with multiple brain metastases (BM).Methods: In this study, 195 patients with EGFR mutations who had multiple BM at preliminary diagnosis were included and retrospectively reviewed. Patients were admitted to receive the following treatments in a multi-disciplinary setting: upfront WBRT followed by EGFR-TKI, concurrent EGFR-TKI and WBRT and upfront EGFR-TKI followed by WBRT. A disease-specific graded prognostic assessment (DS-GPA) was performed for all the patients. The treatment response and overall survival (OS) were assessed as well.Results: The median OS of these patients was 27 months. Objective response rate (ORR) was significantly better in upfront WBRT group than other two groups (P=0.004). Moreover, patients who received upfront WBRT (n=67) had longer OS than the concomitant group (36 vs 25 months; P=0.006) and the upfront EGFR-TKI group (36 vs 25 months; P<0.0001). The prognosis of patients with different DS-GPA scores significantly differed (P<0.0001). In concomitant group and upfront EGFR-TKIs group, patients with higher DS-GPA scores of 2–3 had more favorable prognosis compared with those with lower DS-GPA scores of 0–1.5 (27 vs 25 months; P=0.023). Patients who received EGFR-TKIs concurrently with WBRT had longer OS than those received upfront EGFR-TKIs with high DS-GPA scores. (37 vs 17 months; P=0.023).Conclusion: The use of upfront WBRT for EGFR-mutated lung adenocarcinoma patients with multiple BM can improve ORR and OS. More importantly, patients with high DS-GPA scores are recommended to receive WBRT immediately after EGFR-TKIs therapy.

Temporal muscle thickness is an independent prognostic marker in melanoma patients with newly diagnosed brain metastases

ObjectivesThe purpose of this study was to evaluate the prognostic relevance of temporal muscle thickness (TMT) in melanoma patients with newly diagnosed brain metastases.MethodsTMT was retrospectively assessed in 146 melanoma patients with newly diagnosed brain metastases on cranial magnetic resonance images. Chart review was used to retrieve clinical parameters, including disease-specific graded prognostic assessment (DS-GPA) and survival times.ResultsPatients with a TMT > median showed a statistically significant increase in survival time (13 months) compared to patients with a TMT < median (5 months; p < 0.001; log rank test). A Cox regression model revealed that the risk of death was increased by 27.9% with every millimeter reduction in TMT. In the multivariate analysis, TMT (HR 0.724; 95% 0.642–0.816; < 0.001) and DS-GPA (HR 1.214; 95% CI 1.023–1.439; p = 0.026) showed a statistically significant correlation with overall survival.ConclusionTMT is an independent predictor of survival in melanoma patients with brain metastases. This parameter may aid in patient selection for clinical trials or to the choice of different treatment options based on the determination of frail patient populations.

Disease-specific graded prognostic assessment lung cancer update

Lung cancer accounts for almost 30% of cancer deaths. Length of survival after diagnosis of metastatic lung cancer, however, spans a significant range today. While some patients still only survive in the order of a few weeks to months, an increasing percentage are living years due to the recognition of different types of lung cancer genetics and the ability to treat patients in a personalized fashion with targeted therapies.

Generation of a New Disease-specific Prognostic Score for Patients With Brain Metastases From Small-cell Lung Cancer Treated With Whole Brain Radiotherapy (BMS-Score) and Validation of Two Other Indices

IntroductionPatients with small-cell lung cancer (SCLC) demonstrate an exception in the treatment of brain metastases (BM), because in patients with SCLC whole brain radiotherapy (WBRT) only is the preferred treatment modality. The purpose of this study was to develop a prognostic score for patients with brain metastases from SCLC treated with WBRT. Patients and MethodsThe present study was conducted utilizing a single-institution, previously described, retrospective database of patients with SCLC who were treated with WBRT (n = 221). Univariate and multivariate analyses were performed to generate the “brain metastases from SCLC score” (BMS score) based on favorable prognostic factors: Karnofsky performance status (KPS > 70), extracerebral disease status (stable disease/controlled), and time of appearance of BM (synchronous). Furthermore, the disease-specific graded prognostic assessment score as well as the recursive partitioning analysis (RPA) were performed and compared with the new BMS score by using the log-rank (Mantel-Cox) test. ResultsBMS score and RPA showed the most significant differences between classes (P < .001). BMS score revealed a mean overall survival (OS) of 2.62 months in group I (0-1 points), 6.61 months in group II (2-3 points), and 12.31 months in group III (4 points). The BMS score also identified the group with the shortest survival (2.62 months in group I), and the numbers of patients in each group were most equally distributed with the BMS score. ConclusionThe new BMS score was more prognostic than the RPA and disease-specific graded prognostic assessment scores. The BMS score is easy to use and reflects known prognostic factors in contemporary patients with SCLC treated with WBRT. Future studies are necessary to validate these findings.

Survival time following resection of intracranial metastases from NSCLC-development and validation of a novel nomogram

BackgroundBrain metastases (BM) from non-small cell lung cancer (NSCLC) are the most frequent intracranial tumors. To identify patients who might benefit from intracranial surgery, we compared the six existing prognostic indexes(PIs) and built a nomogram to predict the survival for NSCLC with BM before they intended to receive total intracranial resection in China.MethodsFirst, clinical data of NSCLC presenting with BM were retrospectively reviewed. All of the patients had received total intracranial resection and were randomly distributed to developing cohort and validation cohort by 2:1. Second, we stratified the cohort using a recursive partitioning analysis(RPA), a score index for radiosurgery (SIR), a basic score for BM (BS-BM), a Golden Grading System (GGS), a disease-specific graded prognostic assessment (DS-GPA) and by NSCLC-RADES. The predictive power of the six PIs was assessed using the Kaplan–Meier method and the log-rank test. Third, univariate and multivariate analysis were explored, and the nomogram predicting survival of BMs from NSCLC was constructed using R 3.2.3 software. The concordance index (C-index) was calculated to evaluate the discriminatory power of the nomogram in the developing cohort and validation cohort.ResultsBS-BM could better predict survival of patients before intracranial surgery compared with other PIs. In the final multivariate analysis, KPS at diagnosis of BM, metachronous or synchronous BM and the histology of lung cancer appeared to be the independent prognostic predictors for survival. The C-index in the developing cohort and validation cohort were 0.75 and 0.71 respectively, which was better than the C-index of the other six PIs.ConclusionsThe new nomogram is a promising tool in further choosing the candidates for intracranial surgery among NSCLC with BM and in helping physicians tailor suitable treatment options before operation in clinical practice.

Validation of the Disease-Specific GPA for Patients With 1 to 3 Synchronous Brain Metastases in Newly Diagnosed NSCLC

BackgroundThe disease-specific graded prognostic assessment (DS-GPA) for brain metastases is a powerful prognostic tool but has not been validated for patients with synchronous brain metastases (SBM) in newly diagnosed non–small-cell lung cancer (NSCLC). Patients and MethodsWe identified patients with newly diagnosed NSCLC with 1 to 3 SBM treated with stereotactic radiosurgery (SRS) between 1997 and 2012. We included patients whose brain metastases were treated with SRS alone or combined SRS and whole-brain radiotherapy (WBRT). Patients were stratified according to NSCLC DS-GPA to evaluate the accuracy of survival estimates. ResultsOne hundred sixty-four patients were treated with either SRS alone (n = 85; 52%) or SRS and WBRT (n = 79; 48%). Median overall survival (OS) stratified according to DS-GPA of 0 to 1, 1.5 to 2, 2.5 to 3, and 3.5 to 4 were 2.8, 6.7, 9.8, and 13.2 months, respectively, consistent with OS reported for brain metastases in NSCLC DS-GPA (3.0, 6.5, 11.3, and 14.8 months, respectively). No difference in median progression-free survival or OS was noted with combined use of SRS and WBRT: 6.0 versus 6.1 months (P = .81) and 8.5 versus 9.1 months (P = .093), respectively. In multivariable analysis, Karnofsky performance status (hazard ratio [HR], 0.98; P = .008), extracranial metastases (HR, 0.498; P = .0003), squamous histology (HR, 1.81; P = .02), and number of brain metastases (2 vs. 1; HR, 1.504; P = .04, and 3 vs. 1; HR, 1.66; P = .05) were significant predictors of OS. ConclusionThe DS-GPA accurately estimates the prognosis of patients with SBM in newly diagnosed NSCLC. Patients with synchronous brain metastasis in newly diagnosed NSCLC should be carefully stratified for consideration of aggressive therapy.

Establishment of disease-specific graded prognostic assessment for patients with hepatocellular carcinoma and spinal metastasis.

433 Background: Spinal metastasis (SM) of hepatocellular carcinoma (HCC) is a crucial clinical problem. It shows heterogenous length of survival suggesting a need for predicting prognosis. In this study, we aimed to develop and propose a graded prognostic assessment of SM of HCC (HCC-SM GPA). Methods: We previously reported the outcomes of 192 HCC patients with SM who received radiotherapy from April 1992 to February 2012. Prognostic factors with significant effects on survival in that study were used to establish the HCC-SM GPA. Validation was performed using an independent cohort of 63 patients recruited from September 2011 to March 2016. Results: We developed HCC-SM GPA using the following factors: Eastern Cooperative Oncology Group performance status ( &lt; 2: 0, &gt; 3: 1 point), controlled primary HCC (Yes: 0, No: 2 points), and extrahepatic metastases other than bone (No: 0, Yes: 1 points). Patients were stratified into low (GPA = 0), intermediate (GPA = 1–2), and high risk (GPA = 3–4). When applied to the validation cohort, the HCC-SM GPA determined median survival durations of 13.6, 4.8, and 2.6 months and 1-year overall survival rates of 58.3%, 8.9%, and 7.3% for the low-, intermediate-, and high-risk patient groups, respectively (p &lt; 0.001). Conclusions: Our newly proposed HCC-SM GPA successfully predicted survival outcome. This index might be a useful tool for making treatment decision.

Timing of Brain Radiation Therapy Impacts Outcomes in Patients with Non-small Cell Lung Cancer Who Develop Brain Metastases

背景与目的放疗联合化疗或靶向治疗仍然是非小细胞肺癌脑转移患者的首选治疗。本研究旨在探讨脑放疗时机的选择及推迟脑放疗对于患者疗效和生存期的影响。方法2003年5月-2015年12月, 就诊于我中心确诊为非小细胞肺癌脑转移且接受过脑放疗及全身治疗(包括化疗和靶向治疗)的患者共198例入组了本研究。127例接受了同时性的全身治疗和脑放疗(早放疗组)。71例患者接受了延迟性的脑放疗:完成至少2周期全身治疗后才接受脑放疗(晚放疗组)。早放疗组和晚放疗组患者治疗前的脑转移预后评分(DS-GPA评分)均衡无偏倚。结果早放疗组患者的中位生存时间(overall survival, OS)与晚放疗组相比明显延长(17.9个月 vs 12.6个月, P=0.038), 早放疗组患者的无进展生存期(progression-free survival, PFS)也优于晚放疗组(4.0个月 vs 3.0个月, P < 0.01)。3级-4级放化疗不良反应的发生率两组间无明显差异。确诊脑转移后, 一线使用酪氨酸激酶抑制剂(tyrosine kinase inhibitor, TKI)药物可能延长患者的OS(17.9个月 vs 15.2个月, P=0.289), 但无明显统计学差异。在整个疾病进展过程中曾经使用TKI类药物与从未使用过TKI药物相比, 患者的OS延长(20.0个月 vs 10.7个月, P < 0.01)。结论对于非小细胞肺癌脑转移患者, 推迟脑放疗可能会影响患者的生存期。这一发现仍需要前瞻性多中心的随机对照研究来证实。

Graded Prognostic Index for Gastroesophageal Cancer with Brain Metastases.

2022Background: Brain metastasis (BM) is a rare but serious neurologic complication of gastro esophageal cancers (GEC). The Disease Specific Graded Prognostic Assessment (DS-GPA) which is based solely on Karnofsky performance scale (KPS) is a commonly used prognostic index in patients with BM. We evaluated DS-GPA and other potential prognostic factors for overall survival (OS) in GECBM at our institution. Methods: With IRB approval, the Cleveland Clinic Brain Tumor and Neuro-Oncology Center’s database was used to identify GECBM patients treated between 2002 and 2014. Overall survival (OS) from the diagnosis of GECBM was the primary endpoint. Cox proportional hazards models with stepwise variable selection were used to identify independent prognostic factors. Results: Sixty three patients with median age of 62 years (range; 33-79), were included for analysis. KPS was 90-100 in 22 patients (38%), 70-80 in 30 (52%) and 3 BM in ...

Prognostic indices in stereotactic radiotherapy of brain metastases of non-small cell lung cancer.

BackgroundOur purpose was to analyze the long-term clinical outcome and to identify prognostic factors after Linac-based stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) on patients with brain metastases (BM) from non-small cell lung cancer (NSCLC).Materials and MethodsWe performed a retrospective analysis of survival on 90 patients who underwent SRS or FSRT of intracranial NSCLC metastases between 04/2004 and 05/2014 that had not undergone prior surgery or whole brain radiotherapy (WBRT) for BM. Follow-up data was analyzed until May 2015. Potential prognostic factors were examined in univariable and multivariable analyses. The Golden Grading System (GGS), the disease-specific graded prognostic assessment (DS-GPA), the RADES II prognostic index as well as the NSCLC-specific index proposed by Rades et al. in 2013 (NSCLC-RADES) were calculated and their predictive values were tested in univariable analysis.ResultsThe median follow-up time of the surviving patients was 14 months.The overall survival (OS) rate was 51 % after 6 months and 29.9 % after 12 months.Statistically significant factors of better OS after univariable analysis were lower International Union Against Cancer (UICC) stage at first diagnosis, histology of adenocarcinoma, prior surgery of the primary tumor and lower total BM volume. After multivariable analysis adenocarcinoma histology remained a significant factor; higher Karnofsky Performance Score (KPS) and the presence of extracranial metastases (ECM) were also significant.The RADES II and the NSCLC-RADES indices were significant predictors of OS. However, the NSCLC-RADES failed to differentiate between intermediate- and low-risk patients. The DS-GPA and GGS were not statistically significant predictors of survival in univariable analysis.ConclusionThe ideal prognostic index has not been defined yet. We believe that more specific indices will be developed in the future. Our results indicate that the histologic subtype of NSCLC could add to the prognostic value of specialized future indices. The RADES II index had the highest predictive value in the examined patient cohort.