Recursive Partitioning Analysis Class Research Articles

The role of surgery in recurrent local cerebral metastases: a multi-institutional retrospective analysis.

Local recurrent brain metastases are defined as lesions that recur in the brain at the same site after a previous local therapy. In patients already submitted to surgery, a second operation may be potentially challenging due to scar formation, infiltration of cerebral vessels or eloquent brain areas and local effect of previous radiotherapy. The aim of this study is to retrospectively review the results and complications of a second surgical treatment in a series of local recurrent lesions and to review the literature on this topic. 37 patients submitted to surgery for a local, histologically confirmed, recurrent brain metastases between 2000 and 2022 were retrospectively analyzed with respect to the following parameters: age, histology, anatomic location, time to recurrence, previous radiotherapy, size of recurrent tumors, preoperative and postoperative Karnofsky Performance Status(KPS) score, recursive partitioning analysis (RPA) class and graded prognostic assessment (GPA) score, surgery-related complications and the presence of further cerebral metastases. Overall survival (OS) was calculated using the Kaplan-Meier method. A multivariate Cox proportional hazard model was developed using stepwise regression (forwards selection) with predictive variables that were significant in the univariate analyses. A significant improvement of post-operative KPS status was obtained after second surgery. At multivariate analysis better results in terms of OS were achieved in patients with a pre-operative KPS ≥ 70 and in patients who had received radiotherapy after the initial surgery. No significant postoperative complications related to previous treatments were observed. Surgical resection of local recurrent brain metastases may improve patients ́ neurologic conditions allowing more time for systemic therapies to act with a low incidence of surgery-related morbidity and mortality. However, careful patient selection with a fair pre-operative clinical status seems mandatory to achieve the best post-operative results, since uniform treatment-paradigms cannot be established yet, due to the highly heterogeneous patient cohort.

Patterns of Care for Brain Metastases in Asia: A Real-World Survey Conducted by the Federation of Asian Organizations for Radiation Oncology.

To report the patterns of care for brain metastases (BMs) in the Federation of Asian Organizations for Radiation Oncology (FARO). Overall, 37 questions were prepared. The survey was conducted online using Google Forms, and the URL was distributed to members of the FARO research committee. Radiation oncologists associated with FARO responded to the questionnaire between May 2023 and June 2023, and their answers were analyzed. Responses were received from 32 radiation oncologists in 13 countries participating in FARO. Twenty-six physicians (81.3%) were affiliated with academic centers, and 22 (68.8%) were able to perform stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (fSRT) for BMs at their institution. The most typically used prognostic index for BM was the recursive partitioning analysis classification (17 physicians, 53.1%). The maximum number of BMs indicated for SRT/SRS was ≤three (11 physicians, 34.4%), whereas eight (25.0%) physicians answered for 6-10 BMs. The maximum size of BMs considered for SRS/fSRT was ≤3 cm (14 physicians, 43.8%), whereas nine (28.1%) answered that SRS/fSRT was preferred if the maximum size was >4 cm. When whole-brain radiotherapy (RT) was indicated, hippocampal avoidance and memantine usage were limited to 50.0% and 25.0% of patients, respectively. The most typical RT modality after BM resection was SRS/fSRT alone, regardless of whether the margin was positive (19 physicians, 59.4%) or negative (13 physicians, 40.6%). We report the survey results of the patterns of care for BMs in the FARO. This survey was conducted only among a limited number of FARO members. Since many respondents were affiliated with relatively large-scale academic centers, large-scale surveys, including community hospitals, are warranted for future initiatives.

Therapy Intensity Outweighs the Prognostic Importance of the Timing of Chemoradiotherapy in Newly Diagnosed Glioblastoma Patients.

To investigate the significance of the timing of chemoradiotherapy together with clinical and laboratory features in newly diagnosed glioblastoma. Clinical and laboratory parameters of 209 patients with glioblastoma potentially influencing overall (OS) and progression-free (PFS) survival were analyzed in univariable and multivariable models. On univariable analyses, Karnofsky performance status (p<0.001), recursive partitioning analysis (RPA) class (p<0.001), O6-methylguanine-DNA methyltransferase (MGMT)-status (p<0.001), extent of resection (p<0.001), radiotherapy dose (p=0.01), and the number of adjuvant temozolomide (TMZ) cycles (p<0.001) were significantly associated with OS. Additionally, MGMT-status (p<0.001), extent of resection (p=0.03), surgical site infections (p=0.02), and the number of adjuvant TMZ cycles (p<0.001) were significantly associated with PFS. Multivariable analysis identified radiotherapy dose as the only independent predictor (p=0.049) of OS. MGMT-status (p=0.02) and the number of adjuvant TMZ cycles (p<0.001) were independent predictors of PFS. The timing of chemoradiotherapy did not play a prognostic role. For OS, the radiotherapy dose, and for PFS, MGMT-status and the number of adjuvant TMZ cycles were identified as independent prognostic factors.

Evolving consolidation patterns and outcomes for a large cohort of patients with primary CNS lymphoma

AbstractConsolidation for primary central nervous system lymphoma (PCNSL) after induction chemoimmunotherapy include whole-brain radiotherapy (WBRT; ≤24 Gy reduced-dose [RD], >24 Gy standard-dose) and cytarabine, nonmyeloablative chemotherapy (NMC), or autologous hematopoietic cell transplantation (AHCT). Comparative outcomes are lacking. Outcomes from 1983-2020 were stratified by decade and Memorial Sloan Kettering Cancer Center recursive partitioning analysis (RPA) class. Clinicodemographic associations were analyzed by multinomial logistic regression. Progression-free survival (PFS) and overall survival (OS) were analyzed by proportional hazards. Of 559 patients, 385 (69%) were consolidated. Median follow-up and OS were 7.4 and 5.7 years, respectively. WBRT use declined (61% (1990s) vs 12% (2010s)), whereas AHCT (4% (1990s) vs 32% (2010s)) and NMC (27% (1990s) vs 52% (2010s)) rose. Compared with RPA 1, RPA 2 was more likely to receive NMC. Those with partial response to induction were less likely to receive AHCT (odds ratio, 0.36; P = .02). Among 351 with complete response to consolidation, only receipt of rituximab, methotrexate, procarbazine, and vincristine induction was associated with improved PFS (hazard ratio, 0.5; P = .006). Among RPA 1, median PFS and OS were not reached for AHCT or RD-WBRT, vs 2.5 and 13.0 years, respectively, after NMC. Among RPA class 3, median PFS and OS after RD-WBRT were 4.6 and 10 years, vs 1.7 and 4.4 years after NMC. No significant adjusted survival differences were seen across consolidation strategies. NMC is increasingly used in lieu of RD-WBRT despite a trend toward less favorable PFS. RD-WBRT can be considered in patients ineligible for AHCT.

Incorporating Supramaximal Resection into Survival Stratification of IDH-wildtype Glioblastoma: A Refined Multi-institutional Recursive Partitioning Analysis.

To propose a novel recursive partitioning analysis (RPA) classification model in patients with IDH-wildtype glioblastomas that incorporates the recently expanded conception of the extent of resection (EOR) in terms of both supramaximal and total resections. This multicenter cohort study included a developmental cohort of 622 patients with IDH-wildtype glioblastomas from a single institution (Severance Hospital) and validation cohorts of 536 patients from three institutions (Seoul National University Hospital, Asan Medical Center, and Heidelberg University Hospital). All patients completed standard treatment including concurrent chemoradiotherapy and underwent testing to determine their IDH mutation and MGMTp methylation status. EORs were categorized into either supramaximal, total, or non-total resections. A novel RPA model was then developed and compared with a previous Radiation Therapy Oncology Group (RTOG) RPA model. In the developmental cohort, the RPA model included age, MGMTp methylation status, Karnofsky performance status, and EOR. Younger patients with MGMTp methylation and supramaximal resections showed a more favorable prognosis [class I: median overall survival (OS) 57.3 months], whereas low-performing patients with non-total resections and without MGMTp methylation showed the worst prognosis (class IV: median OS 14.3 months). The prognostic significance of the RPA was subsequently confirmed in the validation cohorts, which revealed a greater separation between prognostic classes for all cohorts compared with the previous RTOG RPA model. The proposed RPA model highlights the impact of supramaximal versus total resections and incorporates clinical and molecular factors into survival stratification. The RPA model may improve the accuracy of assessing prognostic groups. See related commentary by Karschnia et al., p. 4811.

Outcomes and relapse patterns in primary central nervous system lymphoma: Longitudinal analysis of 559 patients diagnosed from 1983 to 2020.

Contemporary outcomes and relapse patterns in primary CNS lymphoma (PCNSL) are lacking. We analyzed factors associated with relapse in a large cohort with extensive follow-up. T1-post-contrast-enhancing disease was characterized in immunocompetent PCNSL (diffuse large B-cell) patients from 1983 to 2020. Patients were stratified by response to induction and consolidation (complete/unconfirmed [CR/CRu], partial, stable, progression [POD]). Refractory was POD during (or relapse ≤3 months of) induction. Initial relapse site was categorized as local (involving/adjacent to baseline), distant intraparenchymal, leptomeningeal, or other. Progression-free (PFS) and overall survival (OS) were assessed with proportional hazards. Cumulative incidence with competing risks was used to assess local relapse. Median follow-up was 7.4 years (N = 559). Most (321, 57%) were recursive partitioning analysis class 2 (age ≥50, Karnosfky Performance Status [KPS] ≥70). Most had supratentorial (420, 81%), multifocal (274, 53%), bilateral (224, 43%), and deep structure involvement (314, 56%). Nearly all received methotrexate-based induction (532, 95%). There was no difference in PFS or OS from consolidation based on initial response to induction (CR/CRu vs PR) in patients who ultimately achieved a CR/CRu to consolidation. PFS at 1-, 5 years for 351 patients with CR/CRu to consolidation was 80% (95% confidence interval [95% CI]: 76%-84%) and 46% (95% CI: 41%-53%), respectively; 1-year cumulative incidence of local versus nonlocal relapse was 1.8% versus 15%, respectively. For 97 refractory patients, 1-year cumulative incidence of local versus nonlocal relapse was 57% versus 42%, respectively. Deep structure involvement (HR 1.89, 95% CI: 1.10%-3.27%) was associated with local relapse in refractory patients. We report the first comprehensive relapse patterns in a large PCNSL cohort. While relapses post-CR to consolidation are typically distant and unpredictable, refractory patients had a relatively high incidence of local relapse. These findings can help optimize multimodality therapy for this highest-risk population.

Intensity-Modulated Reirradiation Therapy With Nivolumab in Recurrent or Second Primary Head and Neck Squamous Cell Carcinoma

Intensity-modulated radiation therapy (IMRT) reirradiation of nonmetastatic recurrent or second primary head and neck squamous cell carcinoma (HNSCC) results in poor progression-free survival (PFS) and overall survival (OS). To investigate the tolerability, PFS, OS, and patient-reported outcomes with nivolumab (approved standard of care for patients with HNSCC) during and after IMRT reirradiation. In this multicenter nonrandomized phase 2 single-arm trial, the treatment outcomes of patients with recurrent or second primary HNSCC who satisfied recursive partitioning analysis class 1 and 2 definitions were evaluated. Between July 11, 2018, and August 12, 2021, 62 patients were consented and screened. Data were evaluated between June and December 2023. Sixty- to 66-Gy IMRT in 30 to 33 daily fractions over 6 to 6.5 weeks with nivolumab, 240 mg, intravenously 2 weeks prior and every 2 weeks for 5 cycles during IMRT, then nivolumab, 480 mg, intravenously every 4 weeks for a total nivolumab duration of 52 weeks. The primary end point was PFS. Secondary end points included OS, incidence, and types of toxic effects, including long-term treatment-related toxic effects, patient-reported outcomes, and correlatives of tissue and blood biomarkers. A total of 62 patients were screened, and 51 were evaluable (median [range] age was 62 [56-67] years; 42 [82%] were male; 6 [12%] had p16+ disease; 38 [75%] had salvage surgery; and 36 [71%.] had neck dissection). With a median follow-up of 24.5 months (95% CI, 19.0-25.0), the estimated 1-year PFS was 61.7% (95% CI, 49.2%-77.4%), rejecting the null hypothesis of 1-year PFS rate of less than 43.8% with 1-arm log-rank test P = .002 within a 1-year timeframe. The most common treatment-related grade 3 or higher adverse event (6 [12%]) was lymphopenia with 2 patients (4%) and 1 patient each (2%) exhibiting colitis, diarrhea, myositis, nausea, mucositis, and myasthenia gravis. Functional Assessment of Cancer Therapy-General and Functional Assessment of Cancer Therapy-Head and Neck Questionnaire quality of life scores remained stable and consistent across all time points. A hypothesis-generating trend favoring worsening PFS and OS in patients with an increase in blood PD1+, KI67+, and CD4+ T cells was observed. This multicenter nonrandomized phase 2 trial of IMRT reirradiation therapy and nivolumab suggested a promising improvement in PFS over historical controls. The treatment was well tolerated and deserves further evaluation. ClinicalTrials.gov Identifier: NCT03521570.

Prognostic Factors and Impact of Therapeutic Intervention in Patients With Brain Metastases at the Initial Presentation.

Background Studies investigating the normative characteristics and prognosis of patients diagnosed with brain metastases (BMs) at the onset of cancer are scarce. Therefore, we analyzed real-world treatment options. Methodology This retrospective study enrolled 112 patients newly diagnosed with BM between May 2006 and October 2021. The variables examined included patients' age, sex, recurrence split analysis, Glasgow prognostic score (GPS), number of lesions, tumor size, peripheral brain tumor edema, targeted therapy, supportive care, chemotherapy, and date of onset. Prognostic factors were assessed using recursive partitioning analysis (RPA), graded prognostic assessment (GPA) scores, and GPS scoring, with magnetic resonance imaging (MRI) andcomputed tomography (CT) studies. Primary treatment comprised whole-brain radiotherapy (WBRT), with regular follow-up. Results Data from 112 survivors were analyzed, revealing a median overall survival time (MST) of 7.7 months, with some patients surviving beyond 24 months post-WBRT. Univariate analysis revealed associations between MST and RPA class, GPS, and treatment modalities (including targeted therapy and chemotherapy). RPA class 2, GPSof 0, and targeted therapy were identified as predictors of better prognosis in the multivariate analysis. In the subgroup not receiving chemotherapy, no significant difference in prognosis was seen between groups with or without WBRT. Conclusions Alongside RPA, scores indicating chronic inflammatory changes, including GPS, were confirmed as crucial prognostic factors. Moreover, treatment with molecularly targeted drugs correlated with favorable prognoses. The treatment-naïve group exhibited poorer prognoses, and WBRT was not deemed a significant prognostic factor in the chemotherapy group.

Concomitant radiosurgical and targeted oncological treatment improves the outcome of patients with brain metastases from gastrointestinal cancer

BackgroundSo far, only limited studies exist that evaluate patients with brain metastases (BM) from GI cancer and associated primary cancers who were treated by Gamma Knife Radiosurgery (GKRS) and concomitant immunotherapy (IT) or targeted therapy (TT).MethodsSurvival after GKRS was compared to the general and specific Graded Prognostic Assessment (GPA) and Score Index for Radiosurgery (SIR). Further, the influence of age, sex, Karnofsky Performance Status Scale (KPS), extracranial metastases (ECM) status at BM diagnosis, number of BM, the Recursive Partitioning Analysis (RPA) classes, GKRS1 treatment mode and concomitant treatment with IT or TT on the survival after GKRS was analyzed. Moreover, complication rates after concomitant GKRS and mainly TT treatment are reported.ResultsMultivariate Cox regression analysis revealed IT or TT at or after the first Gamma Knife Radiosurgery (GKRS1) treatment as the only significant predictor for overall survival after GKRS1, even after adjusting for sex, KPS group, age group, number of BM at GKRS1, RPA class, ECM status at BM diagnosis and GKRS treatment mode. Concomitant treatment with IT or TT did not increase the rate of adverse radiation effects. There was no significant difference in local BM progression after GKRS between patients who received IT or TT and patients without IT or TT.ConclusionGood local tumor control rates and low rates of side effects demonstrate the safety and efficacy of GKRS in patients with BM from GI cancers. The concomitant radiosurgical and targeted oncological treatment significantly improves the survival after GKRS without increasing the rate of adverse radiation effects. To provide local tumor control, radiosurgery remains of utmost importance in modern GI BM management.

Outcomes of Gamma Knife Radiosurgery for Brain Metastases in the Motor Cortex.

To study the clinical, imaging, and survival outcomes in patients with motor cortex brain metastases treated with stereotactic radiosurgery (SRS). Imaging and clinical data were obtained from our prospective patient registry. Tumor volumes were obtained from serial imaging data. The outcomes of 208 patients with metastases involving the motor cortex who underwent SRS between 2012 and 2021 were analyzed. A total of 279 metastases (0.01 cm 3 -12.18 cm 3 , mean 0.74 cm 3 ) were irradiated. The SRS margin dose varied from 10 to 20 Gy (mean 16.9 Gy). The overall tumor control rate was 97.8%. Perilesional edema was noted in 69 (25%) tumors at presentation. Adverse radiation effects (ARE) were noted in 6% of all tumors but were symptomatic in only 1.4%. Median time to appearance of symptomatic ARE was 8 months. Edema without ARE was observed in 13%. New focal seizures were noted in 5 patients (2%) and new generalized seizures in 1 patient (0.3%). Thirty-six patients (17%) presented with motor deficits. At final follow-up, 32 (85%) were improved or unchanged, 13 (41%) had a normal examination, 10 (31%) had mild deficits, and 9 (28%) still had moderate deficits. New remote brain metastases were found in 31% of patients at a median of 8 months. After treatment, the Karnofsky performance score distribution of the population showed an overall right shift and a median survival of 10 months. Patients with incidentally found brain metastases had significantly better survival than those presenting with deficits (median 13 vs 9 months) ( P = .048). Absence of a neurological deficit, recursive partitioning analysis Class I and II, and dose >18 Gy were each associated with a significant survival advantage. SRS for motor cortex metastases is safe in most patients and effective in providing tumor control. Patients treated before neurological deficits develop show better outcomes.

Multi-Institutional Validation of the Recursive Partitioning Analysis for Overall Survival in Patients Undergoing Spine Radiosurgery for Spine Metastasis

The recently published spine radiosurgery (sSRS) recursive partitioning analysis (RPA) for overall survival (OS) separated patients into 3 distinct prognostic groups. We sought to externally validate this RPA using 3 separate multi-institutional datasets. A total of 444 patients were utilized to develop the recently published sSRS RPA predictive of OS in patients with spine metastases. The RPA identified three distinct prognostic classes. RPA Class 1 was defined as KPS >70 and controlled systemic disease (n = 142); RPA Class 2 was defined as KPS>70 with uncontrolled systemic disease or KPS ≤70, age ≥54 and absence of visceral metastases (n = 207); RPA Class 3 was defined as KPS ≤70 and age <54 years or KPS≤70, age ≥54 years and presence of visceral metastases (n = 95). We utilized data from 3 large tertiary care centers to independently validate this RPA. Data from each institution was utilized independently to validate the RPA to minimize confounding based on institutional differences in patient selection. A total of 1,184 patients (221 patients from institution A, 749 institution B, and 214 from institution C) were in the validation cohort and were divided based on their RPA Class. Kaplan-Meier method was used to estimate OS and log-rank test was used to compare OS between RPA classes. In each of the validation cohorts, the median OS was 19.9 months (institution A), 11.0 months (institution B), and 24.4 months (institution C). The patient distribution into RPA classification based on Institution A/B/C was, Class 1 (19.4%, 15.1%, 50.5%), Class 2 (74.7%, 57.7%%, 37.9%), and Class 3 (5.9%, 27.2%%, 11.2%), respectively. The median OS for patients in the validation cohort at Institution A/B/C based on RPA class was Class 1 (54 months, 27.1 months, 50.0 months), Class 2 (15.9 months, 13.0 months, 15.1 months) and Class 3 (6.9 months, 3.5 months, 6.1 months), respectively. Patients in RPA Class 1 had a significantly better OS compared to those in Class 2 of the each of the three external institution validation cohorts (p<0.01). Similarly, patients in RPA Class 2 had a significantly better OS compared to those in Class 3 (p<0.01). The external datasets from three large institutions independently validated the spine SRS RPA successfully for OS in patients undergoing sSRS for spinal metastases. This is the first RPA for OS to have been externally validated using multiple large datasets. Based on this validation, upfront spine SRS is strongly supported for patients in RPA Class 1 and Class 2 and is also cost effective with median OS >11 months for these patients. Patients in RPA Class 3 would benefit most from upfront conventional radiotherapy given their poor expected survival. Given successful external validation, this RPA helps guide physicians to identify those patients with spinal metastases who most benefit from sSRS.

Phase II Randomized Trial of Single- vs. Two-Fraction Spine Stereotactic Radiosurgery for the Treatment of Vertebral Metastases

As systemic therapies improve significantly, more patients with limited metastatic disease are undergoing spine stereotactic radiosurgery (sSRS). High dose (≥24 Gy) single fraction sSRS has been associated with a vertebral compression fracture (VCF) risk of up to 40%. Comparatively, lower dose (16-18 Gy) single fraction sSRS is associated with a fracture risk of 15-20%, with the risk increasing as the dose increases. To mitigate the risk of VCF, while optimizing higher dose delivery, some have advocated utilizing two-fraction sSRS regimen. Therefore, we designed a phase II randomized trial in which we hypothesized that single fraction sSRS is non-inferior to two-fraction sSRS with respect to VCF but offers patients greater convenience. Inclusion criteria include age ≥18, Karnofsky performance score ≥70, vertebral metastasis from C3 to L5, maximum of three separate sites of metastases, limited paraspinal extension (<5 cm), and no rapid neurological decline. Patients must also be either Recursive Partitioning Analysis Class 1 (KPS >70 AND controlled systemic disease) or Class 2 (KPS >70, uncontrolled systemic disease OR KPS ≤70, age ≥54, no visceral metastases). Exclusion criteria include multiple primary cancers, primary neoplasm of the spine, prior surgery at the site of sSRS, spinal cord compression, bony retropulsion resulting in neurologic deficit, inability to undergo/contraindication to MRI, or diffuse multi-level metastatic spine disease. Our primary hypothesis is that single fraction sSRS (experimental arm - 16-18 Gy) is non-inferior to two fraction sSRS (standard arm - 24 Gy). Furthermore, we hypothesize that both treatment arms will have similar local control, pain control, quality of life and toxicity profiles. The primary endpoint of this trial is the development or progression of VCF at 6 months. Secondary endpoints include local control, pain control, quality of life and toxicity all of which will be assessed at 12 months. For the sample size calculation, we assumed a VCF risk of 17% in the experimental arm and a 7% risk in the standard arm. Based on these calculations, we aim to enroll 130 patients, 65 in each arm. This trial is currently enrolling patients actively, and approximately 30% of expected enrollment has been completed to date. This trial is registered on clinicaltrials.gov: NCT04218617. Pending full accrual. Pending full accrual.

Glasgow prognostic score for assessing the efficacy of whole-brain radiation therapy in cases of recursive partitioning analysis class 2 and class 3 multiple brain metastases: a retrospective study

PurposeWhole-brain radiotherapy (WBRT) may not be beneficial for patients with brain metastases (BMs). The Glasgow Prognostic Score (GPS) is a suggested prognostic factor for malignancies. However, GPS has never been assessed in patients with BMs who have undergone WBRT. The purpose of this study was to determine whether GPS can be used to identify subgroups of patients with BMs who have a poor prognosis, such as recursive partitioning analysis (RPA) Class 2 and Class 3, and who will not receive clinical prognostic benefits from WBRT.Materials and methodsA total of 180 Japanese patients with BMs were treated with WBRT between May 2008 and October 2015. We examined GPS, age, Karnofsky Performance Status (KPS), RPA, graded prognostic assessment (GPA), number of lesions, tumor size, history of brain surgery, presence of clinical symptoms, and radiation doses.ResultsThe overall median survival time (MST) was 6.1 months. seventeen patients (9.4%) were alive more than 2 years after WBRT. In univariate analysis, KPS ≤ 70 (p = 0.0066), GPA class 0–2 (p = 0.0008), > 3 BMs (p = 0.012), > 4 BMs (p = 0.02), patients who received ≥ 3 Gy per fraction (p = 0.0068), GPS ≥ 1 (p = 0.0003), and GPS ≥ 2 (p = 0.0009) were found to significantly decrease the MST. Patients who had brain surgery before WBRT (p = 0.036) had a longer survival. On multivariate analysis, GPS ≥ 1 (p = 0.008) was found to significantly decrease MST.ConclusionOur results suggest that GPS ≥ 1 indicates a poor prognosis in patients undergoing WBRT for intermediate and poor prognosis BMs.

Brain metastasis resection: the impact of fluorescence guidance (MetResect study).

Maximal resection of brain metastases (BMs) improves both progression-free survival and overall survival (OS). Fluorescein sodium (FL) in combination with the YELLOW 560-nm filter is a safe and feasible method for visualizing residual tumor tissue during BM resection. The authors of this study aimed to show that use of FL would positively influence the volumetric extent of resection (EOR) and thus the survival outcome in patients undergoing BM resection. Analyzing their institution's prospective brain tumor registry, the authors identified 539 consecutive patients with BMs (247 women, mean age 62.8 years) by using preoperative high-quality MR images for volumetric analysis. BMs were resected under white light (WL) in 293 patients (54.4%; WL group) and under FL guidance in 246 patients (45.6%; FL group). Sex, age, presurgical Karnofsky Performance Status (KPS), recursive partitioning analysis class, and adjuvant treatment modalities were well balanced between the two groups. Volumetric analysis was performed in a blinded fashion by quantifying pre- and postoperative tumor volume based on gadolinium-enhanced T1-weighted sequences. In the FL group, the postoperative tumor volume was significantly smaller (p = 0.01), and hence the quantitative EOR was significantly larger (p = 0.024) and OS was significantly longer (p = 0.0001) (log-rank testing). Multivariate Cox regression modeling showed that age, presurgical KPS, metastasis status, and FL-guided resection are independent prognostic factors for survival. Compared with WL resection, FL-guided BM resection increased resection quality, significantly improved EOR, and prolonged OS.

Relevance of the Updated Recursive Partitioning Analysis (U-RPA) Classification in the Contemporary Care of Patients with Brain Metastases.

Patients with brain metastases (BMETS) need information about the prognosis and potential value of treatment options to make informed therapeutic decisions, but tools to predict survival in contemporary practice are scarce. We propose an Updated Recursive Partitioning Analysis (U-RPA) instrument to predict survival and benefit from brain-directed treatment (BDT) of contemporary patients. This was a retrospective analysis of patients with BMETS treated between 2017 and 2019. With survival as the primary endpoint, we calculated the U-RPA and generated estimates using Kaplan-Meier curves and hazard ratios. Of 862 eligible patients, 752 received BDT and 110 received best supportive care (BSC). Median overall survival with BDT and BSC was 9.3 and 1.3 months, respectively. Patients in RPA class 1, 2A, 2B and 3 who underwent BDT had median survival of 28.1, 14.7, 7.6 and 3.3 months, respectively. The median survival for patients in RPA 3 who received BDT (n = 147), WBRT (n = 79) and SRS (n = 54) was 3.3, 2.9 and 4.1 months, respectively. The U-RPA defines prognosis estimates, independent of tumor type and treatment modality, which can assist to make value-based care treatment decisions. The prognosis for patients in U-RPA class 2B and 3 remains poor, with consideration for early palliative care involvement in these cases.

Outcomes of single brain metastasis treated with gamma knife stereotaxic radiosurgery(GKSR). Our experience on 103 cases.

Brain metastases (BM) occur in the natural course of malignant tumors in 18-40% of cases. Their management has changed considerably over the past decade thanks to the advent of Gamma knife Stereotactic Radiosurgery (GKSR). We report our experience on Single Brain metastasis treated with (GKSR). Patients treated by Gamma Knife stereotaxic radiosurgery (GKSR) in our institution between 2009 and 2021 for Single BM were recorded retrospectively. A total of 103 patients (n=52; 50.5% females) were included, with a mean age of 56.33±11.33. Breast (n=39, 37.9%) and lung (n=36, 35%) were the common original location for the primary tumors. GKSR alone without prior surgery, radiotherapy, or chemotherapy was achieved in 81.5% (n=84). Thirteen patients (15.1%) progressed in BM volume while finding the appearance of de novo BM in 5 (5.8%) patients. The median percentage of tumor control after radiosurgery treatment was 70% (IQR: 65-78) and only 26.2% (n=27) of patients had >80% tumor control and stability over the median follow-up time of 5 (95% CI, 4-6) months. We found only two cases of radionecrosis (1.9%). The median survival time was 5.21 (IQR, 3-8) months. Retreatment, recursive partitioning analysis (RPA) class, and tumor stability influenced the overall survival of BM respectively (Hazard Ratio adjust (HRa)=5.610,p=0.045; HRa=6.133,p=0.031; HRa=22.463, p=0.036). Stereotaxic Radiosurgery provides good results in terms of Overall survival with fewer neurocognitive disorders.RPA class and tumor control (stability) influenced the overall survival of single BM.

Prognostic factors for non-small cell lung cancer patients with central nervous system metastasis with positive driver genes

Objective: To investigate the prognostic factors of patients with central nervous system (CNS) metastatic non-small cell lung cancer (NSCLC) with positive driver genes. Methods: The clinical data of 103 patients with CNS metastatic NSCLC admitted to Beijing Tongren Hospital from January 2016 to December 2020 were retrospectively analyzed, and the patients were divided into positive driver gene group (patients with driver genes mutation and receiving corresponding targeted therapy) and negative driver gene group. Cox univariate and multivariate regression analyses were performed to identify the factors affecting patients' prognosis, and the receiver operating characteristic curve (ROC) was used to compare the predictive ability of 4 scoring systems [recursive partitioning analysis (RPA) classes, diagnosis-specific graded prognostic assessment (DS-GPA) index, basic score for brain metastasesn (BS-BM) and (lung-molecular graded prognostic assessment (lung-mol GPA)]on patients' prognosis. Results: Among the 103 patients, 48 were males and 55 were females, and aged (64.6±9.7) years old. The median survival time of the 103 patients was 24.0 (95%CI: 20.0-28.0) months, the median survival time of the 59 patients in the positive driver gene group was 33.0 (95%CI: 23.4-42.6) months, the median survival time of the 44 patients in the negative driver gene group was 17.0 (95%CI: 14.4-19.6) months, and the difference was statistically significant (χ2=24.69, P<0.001). The results of Cox multivariate analysis showed that the negative driver genes (HR=3.788, 95%CI: 1.951-7.301, P=0.001), Karnofsky performance status (KPS) score<70 (HR=2.613, 95%CI: 1.185-5.761, P=0.017) and neutrophil-to-lymphocyte ratio (NLR)>3.22 (HR=2.714, 95%CI: 1.157-6.365, P=0.022) were independent risk factors affecting the prognosis of patients with CNS metastatic NSCLC. KPS score<70 (HR=3.719, 95%CI: 1.165-11.876, P=0.027) and no radiotherapy (HR=2.032, 95%CI: 1.033-11.364, P=0.041) were independent risk factors affecting the prognosis of patients with CNS metastatic NSCLC with positive driver genes. ROC curve analysis showed that the area under curve (AUC) value of lung-mol GPA was the highest among the 4 scoring systems (AUC=0.843, 95%CI: 0.731-0.956, P<0.001), and the AUC value of the lung-mol GPA combined scoring system (AUC=0.904, 95%CI: 0.816-0.991, P<0.001) was higher than lung-mol GPA. Conclusions: A low KPS score and no cranial radiation therapy are independent risk factors for the prognosis of patients with CNS metastatic NSCLC with positive driver genes; the lung-mol GPA joint scoring system is more conducive to the prognostic assessment of patients with CNS metastatic NSCLC with positive driver genes.

Is more better? Increased doses of high dose methotrexate and addition of rituximab is associated with improved outcomes in a large primary CNS lymphoma cohort.

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive primary brain tumor. While high dose methotrexate (HDMTX) regimens remain standard of care, it remains unclear if optimization of HDMTX doses and the addition of rituximab provide clinical benefit. Over the last 30 years, standard care given at Memorial Sloan Kettering Cancer Center (MSKCC) has evolved, allowing the comparison of patients receiving different numbers of HDMTX doses and those treated with and without rituximab. The purpose of this study was to describe outcomes based on treatment pattern changes. This single-center, retrospective, IRB-approved study at MSKCC included patients with immunocompetent PCNSL, age ≥18 years and diagnosed between 1/1983-12/2017. Overall survival (OS) was modeled from date of last HDMTX for analyses associating HDMTX and OS. Multivariable Cox regression models estimated hazard ratios (HR) and corresponding 95% confidence intervals (CI). There were 546 patients identified with newly diagnosed PCNSL. Median overall survival (mOS) of the entire population was 4.7 years (95% CI: 3.8-5.7 years); 3.3 years (95% CI: 2.7-3.9 years) in patients diagnosed prior to 2006 and 8.1 years (95% CI: 6.6-11.1 years) in patients diagnosed 2006 onwards. Patients receiving ≥6 doses of HDMTX had improved survival compared to those receiving <6 doses of HDMTX (mOS: 7.8 vs. 4.3 years; P=0.001). Patients receiving induction rituximab had improved OS compared to those who did not receive rituximab (mOS: 10.5 vs. 3.2 years; P<0.0001). Patients receiving ≥6 doses of HDMTX and rituximab had greatest mOS at 13 years, with a 70% reduction in death (HR =0.30; 95% CI: 0.19-0.47) adjusting for treatment era, sex, and recursive partitioning analysis (RPA) classes comprising age and karnofsky performance score (KPS). OS for PCNSL has improved significantly over the last few decades. Patients seem to benefit with ≥6 doses of HDMTX and the addition of rituximab, an effect independent of treatment era, age, and KPS.

Factors Associated With Neurocognitive Impairment Following Chemoradiotherapy in Patients With High-Grade Glioma: Results of a Prospective Trial.

High-grade gliomas (HGG) are highly fatal tumors despite advanced multimodality management. They are also associated with neurocognitive impairment, both due to disease pathology and treatment. We aimed to assess various risk factors responsible for neurocognitive decline in HGG patients undergoing adjuvant chemoradiation. Newly diagnosed HGG patients who underwent maximal safe resection were included. Patients received volumetric modulated arc therapy to a dose of 60 Gy in 30 fractions, along with concurrent temozolomide (TMZ) at a dose of 75 mg/m²/day orally; thereafter adjuvant TMZ (150-200 mg/m² for 5 days), given every 28 days for 6 to 8 cycles. The Mini-Mental State Examination questionnaire was used to measure cognitive impairment of each study patient at various time points. Cox regression model was used for univariate and multivariable analysis of data to establish possible risk factors. Fifty-three patients were enrolled and analyzed. At a median follow-up of 15 months, 30 patients (56.6%) developed cognitive impairment, and 23 patients (43.4%) did not. On univariate analysis, HGG with WHO grade 4, glioblastoma and diffuse midline glioma histology, IDH-wild type, recursive partitioning analysis class IV/V, and only biopsy of primary tumor were significantly associated with neurocognitive impairment, but none of them were independent risk factors on multivariable analysis. Planning target volume and dose received by ipsilateral hippocampus were also significantly correlated with cognitive decline in HGG patients. Decline in neurocognitive functions in HGG patients is multifactorial and can be attributed to an amalgam of various tumor, patient, and treatment-related factors.

Body composition and mortality in men receiving prostate radiotherapy: A pooled analysis of NRG/RTOG 9406 and NRG/RTOG 0126.

To validate the association between body composition and mortality in men treated with radiation for localized prostate cancer (PCa). Secondarily, to integrate body composition as a factor to classify patients by risk of all-cause mortality. Participants of NRG/Radiation Therapy Oncology Group (RTOG) 9406 and NRG/RTOG 0126 with archived computed tomography were included. Muscle mass and muscle density were estimated by measuring the area and attenuation of the psoas muscles on a single slice at L4-L5. Bone density was estimated by measuring the attenuation of the vertebral body at mid-L5. Survival analyses, including Cox proportional hazards models, assessed the relationship between body composition and mortality. Recursive partitioning analysis (RPA) was used to create a classification tree to classify participants by risk of death. Data from 2066 men were included in this study. In the final multivariable model, psoas area, comorbidity score, baseline prostate serum antigen, and age were significantly associated with survival. The RPA yielded a classification tree with four prognostic groups determined by age, comorbidity, and psoas area. Notably, the classification among older (≥70years) men into prognostic groups was determined by psoas area. This study strongly supports that body composition is related to mortality in men with localized PCa. The inclusion of psoas area in the RPA classification tree suggests that body composition provides additive information to age and comorbidity status for mortality prediction, particularly among older men. More research is needed to determine the clinical impact of body composition on prognostic models in men with PCa.