Recursive Partitioning Analysis Class Research Articles

Gamma Knife Radiosurgery for Brain Metastases in Non-Small Cell Lung Cancer Patients Treated with Immunotherapy or Targeted Therapy.

Simple SummaryIn non-small cell lung cancer patients with brain metastases, combined Gamma Knife radiosurgery and immunotherapy or targeted therapy showed an increase in overall survival. The combination of Gamma Knife radiosurgery and immunotherapy or targeted therapy did not increase complications related to radiosurgery. Therefore, the combined treatment seems to be a safe and powerful treatment option for non-small cell lung cancer patients with brain metastases.The combination of Gamma Knife radiosurgery (GKRS) and systemic immunotherapy (IT) or targeted therapy (TT) is a novel treatment method for brain metastases (BMs) in non-small cell lung cancer (NSCLC). To elucidate the safety and efficacy of concomitant IT or TT on the outcome after GKRS, 496 NSCLC patients with BMs, who were treated with GKRS were retrospectively reviewed. The median time between the initial lung cancer diagnosis and the diagnosis of brain metastases was one month. The survival after the initial BM diagnosis was significantly longer than the survival predicted by prognostic BM scores. After the first Gamma Knife radiosurgery treatment (GKRS1), the estimated median survival was 9.9 months (95% CI = 8.3–11.4). Patients with concurrent IT or TT presented with a significantly longer survival after GKRS1 than patients without IT or TT (p < 0.001). These significant differences in the survival were also apparent among the four treatment groups and remained significant after adjustment for Karnofsky performance status scale (KPS), recursive partitioning analysis (RPA) class, sex, and multiple BMs. About half of all our patients (46%) developed new distant BMs after GKRS1. Of note, no statistically significant differences in the occurrence of radiation reaction, radiation necrosis, or intralesional hemorrhage in association with IT or TT at or after GKRS1 were observed. In NSCLC-BM patients, the concomitant use of GKRS and IT or TT showed an increase in overall survival without increased complications related to GKRS. Therefore, the combined treatment with GKRS and IT or TT seems to be a safe and powerful treatment option and emphasizes the role of radiosurgery in modern BM treatment.

Recursive Partitioning Analysis for Local Control Achieved With Stereotactic Body Radiation Therapy for the Liver, Spine, or Lymph Nodes

PurposeThis study aims to develop a local control risk stratification using recursive partitioning analysis (RPA) for patients receiving stereotactic body radiation therapy (SBRT) for metastatic cancer. Methods and MaterialsA single institutional database of 397 SBRT treatments to the liver, spine, and lymph nodes was constructed. All treatments required imaging follow-up to assess for local control. Cox proportional hazards analysis was implemented before the decision tree analysis. The data were split into training (70%), validation (10%), and testing (20%) sets for RPA to optimize the training set. ResultsIn the study, 361 treatments were included in the local control analysis. Two-year local control was 71%. A decision tree analysis was used and the resulting model demonstrated 93.10% fidelity for the validation set and 87.67% for the test set. RPA class 3 was composed of patients with non-small cell lung cancer (NSCLC) primary tumors and treatment targets other than the cervical, thoracic, and lumbar spines. RPA class 2 included patients with primary cancers other than NSCLC or breast and treatments targets of the sacral spine or liver. RPA class 1 consisted of all other patients (including lymph node targets and patients with primary breast cancer). Classes 3, 2, and 1 demonstrated 3-year local controls rates of 29%, 50%, and 83%, respectively. On subgroup analysis using the Kaplan-Meier method, treatments for lymph nodes and primary ovarian disease demonstrated improved local control relative to other treatment targets (P < .005) and primary disease sites (P < .005), respectively. ConclusionsA local control risk stratification model for SBRT to sites of metastatic disease was developed. Treatment target and primary tumor were identified as critical factors determining local control. NSCLC primary lesions have increased local failure for targets other than the cervical, thoracic, or lumbar spines, and improved local control was identified for lymph node sites and breast or ovarian primary tumors.

Prognostic analysis of patients with non-small cell lung cancer harboring exon 19 or 21 mutation in the epidermal growth factor gene and brain metastases

BackgroundIn 1997, the Radiation Therapy Oncology Group (RTOG) put forward the recursive partitioning analysis classification for the prognosis of brain metastases (BMs), but this system does not take into account the epidermal growth factor receptor (EGFR) mutations. The aim of the study is to assess the prognosis of patients with EGFR-mutated non-small cell lung cancer (NSCLC) and BMs in the era of tyrosine kinase inhibitor (TKI) availability.MethodsThis was a retrospective study of consecutive patients with EGFR-mutated (exon 19 or 21) NSCLC diagnosed between 01/2011 and 12/2014 at the Tianjin Medical University Cancer Institute & Hospital and who were ultimately diagnosed with BMs. The patients were stage I-III at initial presentation and developed BMs as the first progression. Overall survival (OS), OS after BM diagnosis (mOS), intracranial progression-free survival (iPFS), response to treatment, and adverse reactions were analyzed.ResultsMedian survival was 35 months, and the 1- and 2- year survival rates were 95.6% (108/113) and 74.3% (84/113). The 3-month CR + PR rates of radiotherapy(R), chemotherapy(C), targeted treatment(T), and targeted treatment + radiotherapy(T+R) after BMs were 63.0% (17/27), 26.7% (4/15), 50.0% (7/14), and 89.7% (35/39), respectively. The median survival of the four treatments was 20, 9, 12, and 25 months after BMs, respectively (P = 0.001). Multivariable analysis showed that < 3 BMs (odds ratio (OR) = 3.34, 95% confidence interval (CI): 1.89–5.91, P < 0.001) and treatment after BMs (OR = 0.68, 95%CI: 0.54–0.85, P = 0.001) were independently associated with better prognosis.ConclusionsThe prognosis of patients with NSCLC and EGFR mutation in exon 19 or 21 after BM is associated with the number of brain metastasis and the treatment method. Targeted treatment combined with radiotherapy may have some advantages over other treatments, but further study is warranted to validate the results.

Quality-of-life trajectories after stereotactic radiosurgery for brain metastases.

Quality of life (QOL) is an important endpoint measure of cancer treatment. The authors' goal was to evaluate QOL trajectories and prognostic value in cancer patients treated with stereotactic radiosurgery (SRS) for brain metastases. Patients who underwent Gamma Knife radiosurgery (GKRS) between January 2016 and November 2019 were prospectively evaluated for QOL using the EQ-5D-3L questionnaire before SRS and at follow-up visits. Only patients who had pre-SRS and at least 1 post-SRS QOL assessment were considered. Fifty-four cancer patients underwent 109 GKRS procedures. The first post-SRS visit was at a median of 2.59 months (range 0.13-21.08 months), and the last post-SRS visit was at 14.72 months (range 2.52-45.21 months) after SRS. There was no statistically significant change in the EQ-5D index score (p = 0.539) at the first compared with last post-SRS visit. The proportion of patients reporting some problems on the EQ-5D dimension of self-care increased during the course of follow-up from 9% (pre-SRS visit) to 18% (last post-SRS visit; p = 0.03). The proportion of patients reporting problems on the EQ-5D dimensions of mobility, usual activities, pain/discomfort, and anxiety/depression remained stable during the course of follow-up (p ≥ 0.106). After adjusting for clinical variables, a higher recursive partitioning analysis (RPA) class (i.e., worse prognostic category) was independently associated with greater odds for EQ-5D index score deterioration (p = 0.050). Upfront whole-brain radiation therapy predicted deterioration of the EQ-5D self-care (p = 0.03) and usual activities (p = 0.024) dimensions, while a greater number of lesions predicted deterioration of the EQ-5D anxiety/depression dimension (p = 0.008). A lower pre-SRS EQ-5D index was associated with shorter survival independently from clinical and demographic variables (OR 18.956, 95% CI 2.793-128.64; p = 0.003). QOL is largely preserved in brain metastasis patients treated with SRS. Higher RPA class, upfront whole-brain radiation therapy, and greater intracranial disease burden are independent predictors of post-SRS QOL deterioration. Worse pre-SRS QOL predicts shorter survival. Assessment of QOL is recommended in brain metastasis patients managed with SRS.

Intensity-Modulated Radiotherapy-Based Reirradiation for Head and Neck Cancer: A Multi-institutional Study by Korean Radiation Oncology Group (KROG 1707).

PurposeThe benefits of reirradiation for head and neck cancer (HNC) have not been determined. This study evaluated the efficacy of reirradiation using intensity-modulated radiotherapy (IMRT) for recurrent or second primary HNC (RSPHNC) and identified subgroups for whom reirradiation for RSPHNC is beneficial.Materials and MethodsA total of 118 patients from seven Korean institutions with RSPHNC who underwent IMRT-based reirradiation between 2006 and 2015 were evaluated through retrospective review of medical records. We assessed overall survival (OS) and local control (LC) within the radiotherapy (RT) field following IMRT-based reirradiation. Additionally, the OS curve according to the recursive partitioning analysis (RPA) suggested by the Multi-Institution Reirradiation (MIRI) Collaborative was determined.ResultsAt a median follow-up period of 18.5 months, OS at 2 years was 43.1%. In multivariate analysis, primary subsite, recurrent tumor size, interval between RT courses, and salvage surgery were associated with OS. With regard to the MIRI RPA model, the class I subgroup had a significantly higher OS than class II or III subgroups. LC at 2 years was 53.5%. Multivariate analyses revealed that both intervals between RT courses and salvage surgery were prognostic factors affecting LC. Grade 3 or more toxicity and grade 5 toxicity rates were 8.5% and 0.8%, respectively.ConclusionIMRT-based reirradiation was an effective therapeutic option for patients with RSPHNC, especially those with resectable tumors and a long interval between RT courses. Further, our patients' population validated the MIRI RPA classification by showing the difference of OS according to MIRI RPA class.

Brain metastases from small cell lung cancer: survival after whole brain radiotherapy versus stereotactic radiosurgery of recursive partitioning analysis class I–II patients

Brain metastases from small cell lung cancer: survival after whole brain radiotherapy versus stereotactic radiosurgery of recursive partitioning analysis class I–II patients

Optimal timing of chemoradiotherapy after surgical resection of glioblastoma: Stratification by validated prognostic classification.

Previous studies examining the time to initiate chemoradiation (CRT) after surgical resection of glioblastoma have been conflicting. To better define the effect that the timing of adjuvant treatment may have on outcomes, the authors examined patients within the National Cancer Database (NCDB) stratified by a validated prognostic classification system. Patients with glioblastoma in the NCDB who underwent surgery and CRT from 2004 through 2013 were analyzed. Radiation Therapy Oncology Group recursive partitioning analysis (RPA) class (III, IV, V) was extrapolated for the cohort. Time intervals were grouped weekly, with weeks 4 to 5 serving as the reference category for analyses. Kaplan-Meier analysis, log-rank testing, and multivariate (MVA) Cox proportional hazards regression were performed. In total, 30,414 patients were included. RPA classes III, IV, and V contained 5250, 20,855, and 4309 patients, respectively. On MVA, no time point after week 5 was associated with a change in overall survival for the entire cohort or for any RPA class subgroup. The periods of weeks 0 to 1 (hazard ratio [HR], 1.18; 95% CI, 1.02-1.36), >1 to 2 (HR, 1.23; 95% CI, 1.16-1.31), and >2 to 3 (HR, 1.11; 95% CI, 1.07-1.15) demonstrated slightly worse overall survival (all P<.03). The detriment to early initiation was consistent across each RPA class subgroup. The current data provide insight into the optimal timing of CRT in patients with glioblastoma and describe RPA class-specific outcomes. In general, short delays beyond 5weeks did not negatively affect outcomes, whereas early initiation before 3weeks may be detrimental.

The Effect of Epidermal Growth Factor Receptor Mutation on Intracranial Progression-Free Survival of Non-Small Cell Lung Cancer Patients with Brain Metastasis Underwent Gamma Knife Radiosurgery

BackgroundThe aim of this study was to survey prognostic factors, particularly those focusing on epidermal growth factor receptor (EGFR) mutations, of patients with non-small cell lung cancer (NSCLC) after Gamma Knife Radiosurgery (GKRS) for metastatic brain tumors.MethodsWe retrospectively reviewed the medical records of 98 patients with NSCLC who underwent GKRS for brain metastases from August 2010 to July 2017. The primary endpoint was progression-free survival (PFS) of the intracranial disease. We analyzed variables such as age, sex, Karnofsky Performance Status, recursive partitioning analysis (RPA) class, smoking status, primary cancer pathology, EGFR mutations, and time to brain metastases as prognostic factors.ResultsThe median overall survival (OS) of the patients was 16 months [95% confidence interval (CI), 13–21 months]. Median systemic PFS and intracranial PFS were 9 months (95% CI, 8–11 months) and 11 months (95% CI, 7–14 months), respectively. Kaplan-Meier survival analysis revealed that the patients with EGFR mutations had longer intracranial PFS than those without EGFR mutation (median intracranial PFS: 19 vs. 10 months with p=0.01) while they had no benefits in OS and systemic PFS. Furthermore, the patients harboring adenocarcinoma had longer OS (p<0.01) and intracranial PFS (p<0.01) and the patients with lower RPA class had longer OS (p=0.02) and intracranial PFS (p=0.03).ConclusionEGFR mutations, primary cancer pathology, and RPA class may be proposed as prognostic factors for intracranial PFS in NSCLC patients after GKRS for brain metastasis in this study.

Patterns of recurrence and outcomes of glioblastoma multiforme treated with chemoradiation and adjuvant temozolomide

OBJECTIVES:To assess the patterns of failure and prognostic factors in Brazilian patients with glioblastoma multiforme (GBM) treated with radiotherapy (RT) and concurrent and adjuvant temozolomide (TMZ).METHODS:Patients with diagnosed GBM post-resection received postoperative RT. TMZ was administered concurrently at 75 mg/m2/day for 28 consecutive days and adjuvant therapy at 150-200 mg/m2/day for 5 days every 28 days. Radiographic failure was defined as any new T1-enhancing lesion or biopsy-confirmed progressive enhancement inside of the radiation field. When possible, patients with recurrence were salvaged with metronomic TMZ, either in combination with a local treatment or alone (surgery or re-irradiation). Several prognostic factors were evaluated for overall survival (OS). Univariate and multivariate analyses were performed to identify significant factors. A p-value <0.05 was considered significant.RESULTS:This study included 50 patients. The median follow-up time was 21 months. The median RT dose was 60 Gy and all patients received concomitant TMZ. During follow-up, 41 (83.6%) failures were observed, including 34 (83%) in-field, 4 (9.7%) marginal, and 3 (7.3%) distant failures. Metronomic TMZ was used as salvage treatment in 22 (44%) cases and in combination with local treatment in 12 (24%) cases. The median OS and progression-free survival times for the entire cohort were 17 and 9 months, respectively. In univariate analysis, the following factors were significant for better OS: maximal surgical resection (p=0.03), Karnofsky Performance Score (KPS)>70 at diagnosis (p=0.01), metronomic TMZ treatment (p=0.038), recursive partitioning analysis class III (p=0.03), and time to failure >9 months (p=0.0001). In multivariate analysis, the following factors remained significant for better OS: metronomic TMZ (p=0.01) and time to failure >9 months (p=0.0001).CONCLUSION:The median OS of Brazilian patients with GBM treated with RT and TMZ was satisfactory. Although TMZ therapy has become the standard of care for patients with newly diagnosed GBM, the recurrence rate is extremely high. Metronomic TMZ as salvage treatment improved survival in these patients.

Correlation of Magnetic Resonance Spectroscopy Changes in Hippocampal and Perihippocampal Regions and Neuro-Psychologic Evaluation with Various Clinical Factors Following Whole Brain Radiotherapy in Brain Metastasis

Objectives: To study the correlation of magnetic resonance spectroscopy (MRS) changes in hippocampal and perihippocampal regions and neuro-psychologic evaluation with various clinical factors following whole brain radiotherapy in brain metastasis. Methods: A total of 33 patients with newly diagnosed brain metastasis, referred to our Department of Radiation Oncology were recruited after a prior informed written consent. All patients underwent baseline clinical/neurological evaluation, detailed MMSE examination, gadolinium enhanced MRI along with MRS (for ratio of Choline: NAA = CNI) from the bilateral hippocampal and perihippocampal areas. All patients then underwent WBRT by two opposing lateral portals on a linear accelerator to a dose of 30 gray in 10 fractions delivered over 2 weeks. Serial evaluations along with MRS and MMSE score were done at 1st, 3rd and 6 months after WBRT. The trends of CNI and MMSE scores at last follow-up were correlated with various clinical factors. Results: Our cohort had 33 patients, predominantly women (M:F, 12:21) with a median age of 47 years, median KPS (Karnofsky performance status) of 80, mean RPA (recursive partitioning analysis) class 2, primary histology (lung, breast, GI, Gy, GU, MUO (metastasis of unknown origin): 10, 11, 2, 4, 4, 2). Median survival of the cohort was 4 months. At the end of 14 months of follow-up 30% of the patients were alive with a mean KPS of 70. Trend in the CNI values with time showed that, KPS (P = 0.079), RPA class (P = 0.079), primary diagnosis site (P = 0.049), number of brain metastasis (P = 0.045) showed statistical significance in terms of change in mean value of CNI value at last follow-up. Site of primary (lung/breast vs. others, P = 0.02) and number of metastasis (solitary/oligo vs. multiple, P = 0.02) showed significant correlation with decline in CNI. The KPS at presentation (< 70 or > 70, P = 0.04); RPA class (class II or higher, P = 0.04); Site of primary (lung/breast vs. others, P = 0.01), presence of extracranial disease (yes or no, P = 0.045), number of metastasis (solitary/oligo vs. multiple, P = 0.06), Size of the largest metastatic lesion (< or > 4 cm, P = 0.02) showed significant correlation with decline in MMSE at last follow-up. Conclusions: Cognitive functioning after WBRT is influenced by a number of factors; patient related, systemic disease burden and local tumor load. Local disease control has significant impact on preservation of neurocognition. The trend in the CNI index and MMSE scores at last follow-up correlated with various factors and can be used as a guide to aid in patient selection for hippocampus- avoidance WBRT.

The usefulness of stereotactic radiosurgery for recursive partitioning analysis class II/III lung cancer patients with brain metastases in the modern treatment era.

Stereotactic radiosurgery (SRS) is considered the initial treatment for lung cancer patients with small-sized and limited number of brain metastases. The objective of this study was to assess clinical outcomes of SRS treatment using CyberKnife (CK) for recursive partitioning analysis (RPA) class II/III patients with 1 to 3 brain metastases from lung cancer and identify which patients in the high RPA class could benefit from SRS.A total of 48 lung cancer patients who received CK-based SRS for their metastatic brain lesions from 2010 to 2017 were retrospectively analyzed. Radiographic response was evaluated during follow-up period. Overall survival (OS) and intracranial progression-free survival (IPFS) were calculated and prognostic variables associated with OS and IPFS were evaluated.Median follow-up time was 6.6 months. Local control rates at 6 months and 1-year following SRS were 98% and 92%, respectively. The median OS of all patients was 8 months. One-year and 2-year OS rates were 40.8% and 20.9%, respectively. In multivariate analysis, uncontrolled primary disease (P = .01) and Eastern Cooperative Oncology Group performance status of 2 or 3 (P = .001) were independent prognostic factors for inferior OS. These 2 factors were also significantly associated with inferior IPFS. In subgroup analysis according to RPA class, primary disease status was the only prognostic factor, showing statistically significant OS differences in both RPA class II and III (controlled vs uncontrolled: 41.1 vs 12.3 months in RPA class II, P = .03; 26.9 vs 4.1 months in RPA class III, P = .01).Our results indicated that SRS could be an effective treatment option for RPA class II/III patients with brain metastases from lung cancer in the modern treatment era. SRS might be particularly considered for patients with controlled primary disease.

408P - Whole brain radiotherapy plus simultaneous in-field boost versus whole brain radiotherapy plus fractionated stereotactic radiotherapy for multiple brain metastases of non-small cell lung cancer

BackgroundBrain metastasis (BM) is common among patients with non-small cell lung cancer (NSCLC). Whole brain radiotherapy (WBRT) plus a radiation boost is a common treatment strategy for such patients. WBRT plus simultaneous in-field boost (WBRT+SIB) and WBRT plus hypo-fractionated stereotactic radiotherapy (WBRT+FSRT) have shown promising outcomes. The current study compared the efficacy and safety of these two treatment strategies. MethodsSixty-six NSCLC patients with multiple BMs who met the inclusion criteria from January 2010 to December 2016 were enrolled. The efficacy and toxicity of WBRT+SIB and WBRT+FSRT were analyzed retrospectively. A Cox proportional hazard model was used to identify prognostic factors. ResultsThe objective response rates in the WBRT+SIB and WBRT+FSRT groups were similar (74.9% and 79.4%, respectively; p=0.5), as was the disease control rate (93.8% and 97.1%, respectively; P=0.3). The median survival time was 15.3 months in the WBRT+SIB group and 25.2 months in the WBRT+FSRT group (p=0.02). The median local progression-free survival was 13 months in the WBRT+SIB group and 17 months in the WBRT+FSRT group (p=0.04). The incidence of 1-3 grade toxicity was slightly lower in the WBRT+FSRT group than the WBRT+SIB group (31.2% vs. 38.2%). Compared to the WBRT+SIB group, the WBRT+FSRT group was associated with a lower risk of mortality (HR=0.6; 95% CI, 0.1-0.7) in the Cox multivariate model. Extracranial metastases, worse recursive partitioning analysis class, and non-surgical treatment of primary lesions were associated with a worse prognosis. ConclusionsCompared to WBRT+SIB, WBRT+FSRT treatment was associated with a better prognosis and slightly less toxicity in patients with multiple BMs from NSCLC. Further studies are warranted to better elucidate the difference and determine the optimal dose/fractionation. Legal entity responsible for the studyJinyi Lang. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Prognostic Value of Neutrophil-to-Lymphocyte Ratio before Cranial Radiotherapy in Non-Small Cell Lung Cancer Patients with Limited Brain Metastases: A Propensity-Score Matched Pair Comparison of Whole-Brain Radiotherapy and Stereotactic Irradiation Alone

Stereotactic irradiation (STI) alone as initial management has emerged as a widely practiced treatment modality for selected non-small cell lung cancer (NSCLC) patients with 1 to 10 small brain metastases. However, no randomized study comparing whole brain radiotherapy (WBRT) versus STI alone has been reported. To better assess the prognosis and guidance for optimal treatment selection of patients with brain metastases, we introduced the neutrophil to lymphocyte ratio (NLR) recognized as a poor prognostic factor in various cancers before cranial radiotherapy. A total of 193 consecutive NSCLC patients with 1 to 10 brain metastases with diameters less than 3cm in our institution were retrospectively analyzed. Patients with leptomeningeal metastasis, those who underwent craniotomy before RT and poor performance status were excluded. The evaluated prognostic factors for OS included gender, neurological deficit, histology, epidermal growth factor receptor (EGFR) mutation status, the number of target, target volume, previous EGFR-tyrosine kinase inhibitor treatment, recursive partitioning analysis (RPA) class and NLR. All factors with a p < 0.05 in univariate analysis were entered into multivariate analysis using Cox regression and matched on a 1:1 basis for these prognostic variables. One hundred seven patients received STI and 86 received WBRT. The median follow-up for the entire cohort was 8.3 months (range, 0.8 - 154 months), 9.3 months for STI group and 7.7 months for WBRT group. Patient characteristics of the entire cohort were balanced in terms of gender, histology, EGFR status, and previous treatment. However, the rates of neurological deficit, the number of target, target volume, poor RPA class, and NLR were significantly larger in the WBRT group. Median overall survival (OS) in STI group and WBRT group was 10.1 months (range, 1.7 - 154 months) and 6.3 months (range, 0.8 - 112 months), respectively (p = 0.047). Univariate analysis showed that factors affecting OS were EGFR status, RPA class, solitary intracranial metastasis and NLR (p <0.05). Multivariate analysis found that NLR less than the cutoff value 3.6 (p = 0.0001) and solitary intracranial metastasis (p = 0.03) were independent favorable prognostic factors affecting OS. Propensity-score matching created a matched cohort of 92 patients (STI: n = 46 and WBRT: n = 46) with similar baseline characteristics. The survival benefit was not found in the STI group compared with the WBRT group (p = 0.56), whereas WBRT group reduced intracranial failure than STI group (p = 0.043). Adjusting for prognostic factors, treatment with either STI or WBRT did not result in any statistically significant difference in OS. NLR prior to cranial radiotherapy could be one of the strongest prognostic factors for NSCLC patients with limited brain metastases, and future prospective clinical investigation to validate its prognostic value is warranted.

Recursive Partitioning Analysis of Patients with Spine Metastases Treated with Stereotactic Body Radiotherapy

Uncertainty exits regarding the outcomes of patients receiving stereotactic body radiotherapy (SBRT) for spinal metastases. We sought to create a prognostic index using recursive partitioning analysis (RPA) for overall survival (OS). After institutional review board (IRB) approval, we performed a retrospective review on 334 patients treated with SBRT between 2005 and 2017. The cohort was split 2:1 into modelling and validation datasets. RPA was performed in the modeling cohort of patients to identify any association of the following variables with OS after spine SBRT: tumor histology, gender, age, race, performance status (KPS), controlled primary, extraosseous metastases, previous surgery, previous radiation therapy, time from primary diagnosis to treatment with SBRT, extent of spinal disease (single or multiple), spine disease type (bone only, epidural only, or bone plus epidural), paraspinal extension, equivalent dose in 2-Gy fractions (EQD2) for a/b ratio of 2, and EQD2 a/b ratio of 10. Median OS for the entire cohort was 9.8 months (95% CI 7.8-11.8). RPA analysis identified two prognostic groups (p<0.001). RPA1 included patients with bone only disease or extraosseous metastases and controlled primary from breast/prostate primary; RPA2 included extraosseous metastases from non-breast/prostate primary or uncontrolled breast/prostate primary. Median OS was 18.0 months (IQR: 6.9-29.0) and 5.4 months (IQR: 4.1-6.8) for RPA1 and RPA2, respectively. Multivariate Cox regression including the RPA and all other factors found to be significant initially in univariate analysis confirmed the RPA as the most significant variable predicting survival after spine SBRT in the validation data set. Patients treated for spine metastases with SBRT have variability in OS. An RPA classification system was developed with plans to further refine OS outcomes with additional variables. The RPA1 classification can successfully identify patients with sufficiently long expected OS that prospective analysis for late effects could be feasible in this cohort.

Linac-Based Fractionated Stereotactic Radiotherapy with a Micro-Multileaf Collimator for Brainstem Metastasis

To assess the neuroimaging and clinical outcomes in patients with brainstem metastasis (BSM) treated with linac-based fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator. Between May 2007 and January 2017, 24 patients (15 male and 9 female) with BSM (25 lesions: midbrain, 10; pons, 13; and medulla oblongata, 2) were consecutively treated with linac-based fSRT. BSM originated from the lung (n= 18, 75.0%), colon (n= 3, 12.5%), and breast (n= 3, 12.5%). The median patient age was 67.0 (range: 42-80) years. Recursive partition analysis classified 2 patients as class I, 17 as class II, and 5 as class III. Overall survival was calculated using the Kaplan-Meier method. Tumor volume ranged from 0.01 to 7.49 cm3 (median: 0.233 cm3), and patients were treated with a dose of 24-40 Gy in 7-13 fractions. The median OS was 9 months after fSRT (95% confidence interval 4.104-13.896). Large tumor volume, presence of brainstem-related symptoms, poor pretreatment Karnofsky performance status, and recursive partition analysis class III were significantly associated with low overall survival. Tumor volume decreased in 18 metastatic lesions, remained stable in 6, and increased in 1. No patient exhibited permanent radiation injury. Grade 2 nausea and vomiting according to the Common Terminology Criteria for Adverse Events 4.0 occurred in 1 patient who received corticosteroids. Linac-based fSRT with a micro-multileaf collimator delivered in the doses of 24-40 Gy in 7-13 fractions is a safe and effective local therapy for patients with BSM.

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.

The timing of chemoradiotherapy after surgical resection and its impact on overall survival in glioblastoma.

2051 Background: Prior studies examining time to initiate chemoradiotherapy (CRT) after surgical resection (S) in glioblastoma (GBM) have not provided clear consensus on its clinical impact. We sought to evaluate the effect that differential timing of adjuvant therapy may have on overall survival (OS). Methods: With the National Cancer Database (NCDB), patients (pts) with GBM who underwent S and adjuvant CRT from 2004-2013 were analyzed. Analysis was performed for the entire cohort as well as by Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) classes (i.e. I, II, and III). Time from S to CRT was grouped weekly (i.e. 0-1, 1-2, 2-3, 3-4, 4-5, 5-6, 6-7, 7-8, and &gt; 8 weeks). Pts were excluded if they died within the first 8 weeks to account for immortal time bias. Kaplan-Meier analysis, log-rank testing, and multivariate (MVA) Cox proportional hazards regression were performed with OS as the primary outcome. Results: A total of 30,414 pts were included for analysis. RPA class I, II, and III contained 903, 4,347, and 25,164 pts, respectively. The most common time to initiate CRT was week 4-5 (n = 7389), and this group served as reference for survival analysis. On MVA, weeks 0-1 (hazard ratio [HR] 1.18, 95% confidence interval [CI] 1.02-1.35), 1-2 (HR 1.24, CI 1.17-1.32), and 2-3 (HR 1.11, CI 1.07-1.15) demonstrated worse OS (all p &lt; 0.03). For RPA class I pts, week 1-2 (HR 2.07, CI 1.08-3.95) was associated with worse OS (p = 0.028). For RPA class II pts, weeks 1-2 (HR 1.34, CI 1.14-1.57), 2-3 (HR 1.18, CI 1.07-1.31), and 3-4 (HR 1.10, CI 1.0-1.21) were associated with worse OS (all p &lt; 0.05). For RPA class III pts, weeks 0-1 (HR 1.18, CI 1.02-1.38), 1-2 (HR 1.22, CI 1.14-1.3), and 2-3 (HR 1.09, CI 1.05-1.14) were associated with worse OS (all p &lt; 0.03). No time point after week 5 was associated with change in OS for the overall cohort or any RPA class subgroup. Conclusions: These data provide insight into the optimal timing of CRT in GBM and describe RPA-class specific outcomes. In general, OS was negatively impacted if CRT started less than 3 weeks from S. Waiting up to 8 weeks, however, was not detrimental to OS and suggests delaying CRT beyond week 4-5 should be considered if clinically indicated without undue concern.

Metabolic tumor volume of metastatic lymph nodes and survival after total laryngectomy in laryngeal and hypopharyngeal cancer

ObjectivesThe prognostic value of metabolic tumor volume (MTV) in locally advanced laryngeal or hypopharyngeal cancer is established in the setting of chemoradiotherapy, while it remains unknown in the setting of upfront total laryngectomy. Materials and methodsWe retrospectively analyzed 88 patients receiving total laryngectomy and neck dissection, using Cox regression models. Results and conclusionVariables related to metastatic lymph node were associated with overall survival, whereas those related to primary tumor were not. In multivariable models, MTV of metastatic lymph nodes (N-MTV) as a continuous variable (Akaike’s information criterion (AIC), 277.5) was equivalent to pathological nodal status (AIC, 278.2; P = 0.40), and superior to pathological nodal classification as an ordinal variable (AIC, 281.4; P < 0.05) in ability of predicting death. The risk of death was increased by 1.2-fold (95% confidence interval (CI), 1.0–1.4; P = 0.03) every 10-ml increment of N-MTV, while patients with pN+ disease were at a higher risk of death by 2.9-fold (95% CI, 1.0–12.2; P < 0.05) compared with patients with pN0 disease. Using recursive partitioning analysis (RPA), we classified the patients as having a low, intermediate, or high risk of death on the basis of N-MTV and extranodal extension (ENE). This RPA classification system exhibited greater concordance with overall survival than the classification considering pathological nodal status and ENE (AIC, 275.8 versus 281.4; P = 0.02). In the setting of upfront total laryngectomy, N-MTV is a critical predictor of mortality. A staging system in which N-MTV is incorporated may better inform adjuvant treatment decisions.

Craniotomy and Survival for Primary Central Nervous System Lymphoma.

Cytoreductive surgery is considered controversial for primary central nervous system lymphoma (PCNSL). To investigate survival following craniotomy or biopsy for PCNSL. The National Cancer Database-Participant User File (NCDB, n=8936), Surveillance, Epidemiology, and End Results Program (SEER, n=4636), and an institutional series (IS, n=132) were used. We retrospectively investigated the relationship between craniotomy, prognostic factors, and survival for PCNSL using case-control design. In NCDB, craniotomy was associated with increased median survival over biopsy (19.5 vs 11.0 mo), independent of subsequent radiation and chemotherapy (hazard ratio [HR] 0.80, P<.001). We found a similar trend with survival for craniotomy vs biopsy in the IS (HR 0.68, P=.15). In SEER, gross total resection was associated with increased median survival over biopsy (29 vs 10 mo, HR 0.68, P<.001). The survival benefit associated with craniotomy was greater within recursive partitioning analysis (RPA) class 1 group in NCDB (95.1 vs 29.1 mo, HR 0.66, P<.001), but was smaller for RPA 2-3 (14.9 vs 10.0 mo, HR 0.86, P<.001). A surgical risk category (RC) considering lesion location and number, age, and frailty was developed. Craniotomy was associated with increased survival vs biopsy for patients with low RC (133.4 vs 41.0 mo, HR 0.33, P=.01), but not high RC in the IS. Craniotomy is associated with increased survival over biopsy for PCNSL in 3 retrospective datasets. Prospective studies are necessary to adequately evaluate this relationship. Such studies should evaluate patients most likely to benefit from cytoreductive surgery, ie, those with favorable RPA and RC.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Role of Surgery in the Management of Adults With Metastatic Brain Tumors.

Level 1: Surgery + WBRT is recommended as first-line treatment in patients with single brain metastases with favorable performance status and limited extracranial disease to extend overall survival, median survival, and local control. Level 3: Surgery plus SRS is recommended to provide survival benefit in patients with metastatic brain tumors Level 3: Multimodal treatments including either surgery + WBRT + SRS boost or surgery + WBRT are recommended as alternatives to WBRT + SRS in terms of providing overall survival and local control benefits. SURGERY AND RADIATION FOR METASTATIC BRAIN TUMORS QUESTION: Should patients with newly diagnosed metastatic brain tumors undergo surgical resection followed by WBRT, SRS, or another combination of these modalities? Level 1: Surgery + WBRT is recommended as superior treatment to WBRT alone in patients with single brain metastases. Level 3: Surgery + SRS is recommended as an alternative to treatment with SRS alone to benefit overall survival. Level 3: It is recommended that SRS alone be considered equivalent to surgery + WBRT. SURGERY FOR RECURRENT METASTATIC BRAIN TUMORS QUESTION: Should patients with recurrent metastatic brain tumors undergo surgical resection? Level 3: Craniotomy is recommended as a treatment for intracranial recurrence after initial surgery or SRS. SURGICAL TECHNIQUE AND RECURRENCE QUESTION A: Does the surgical technique (en bloc resection or piecemeal resection) affect recurrence? Level 3: En bloc tumor resection, as opposed to piecemeal resection, is recommended to decrease the risk of postoperative leptomeningeal disease when resecting single brain metastases. Does the extent of surgical resection (gross total resection or subtotal resection) affect recurrence? Level 3: Gross total resection is recommended over subtotal resection in recursive partitioning analysis class I patients to improve overall survival and prolong time to recurrence. The full guideline can be found at https://www.cns.org/guidelines/guidelines-treatment-adults-metastatic-brain-tumors/chapter_2.