Median On Overall Survival Research Articles

Real-world outcomes of everolimus-based treatment in a Taiwanese cohort with metastatic HR+/HER2- breast cancer.

Everolimus was the first orally targeted therapy for certain cancers. It was introduced before CDK4/6 inhibitors and is widely used to treat advanced hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. This study presents comprehensive findings including updated data and long-term survival analyses focusing on patients with HR+/HER2- metastatic breast cancer who received everolimus-based treatment. The objectives were to assess the impact of everolimus on overall survival (OS) and progression-free survival (PFS) by treatment line, and to evaluate its role in therapeutic strategies in a real-world setting. We included 299 women aged over 20 years with histologically confirmed HR+/HER2- breast cancer who received everolimus-based treatment from multiple medical centers in Taiwan. Survival curves were generated using the Kaplan-Meier method, with the log-rank test for comparisons. Univariate and multivariate analyses were performed using a Cox proportional hazards regression model. Adverse effects were graded according to the Common Terminology Criteria for Adverse Events version 5.0. The median PFS was 5.6 months, and the median OS was 60.1 months. Patients receiving everolimus treatment in three or more lines and those who underwent chemotherapy prior to everolimus-based treatment had a significantly shorter PFS but longer OS. Patients with liver and central nervous system metastases had significantly shorter PFS and OS. The disease control rate was 51.5%, and the overall response rate was 8.0%. These findings support current guidelines and advocate for the inclusion of everolimus in treatment plans for patients with metastatic HR+/HER2- breast cancer, particularly in late-line treatment, with careful consideration of the benefit-risk profile for each patient.

PATH-26. MIDLINE INVOLVEMENT IS ASSOCIATED WITH ABERRANT RB1 SIGNALING IN PATIENTS WITH GRADE 4 IDH-MUTANT ASTROCYTOMA

Abstract BACKGROUND The prognostic factors impacting the survival of grade 4 IDH-mutant astrocytoma treated with standard radiation/temozolomide are not well-described. METHODS A retrospective cohort was generated of all patients diagnosed at Mayo Clinic with grade 4 IDH-mutant astrocytoma (2021 WHO Classification) on initial diagnosis between 2002-2023, and who received standard radiation/temozolomide. The impact of patient, tumor and molecular variables on overall survival (OS) and progression-free survival (PFS) was evaluated using survival analyses and Cox regression models. RESULTS Fifty-eight patients were identified. The median age was 36 years, 64% were male and 93% were white. The median follow up was 3.3 years. The median OS and PFS were 6.9 years and 2.4 years, respectively. CDKN2A/B homozygous deletion significantly reduced both OS (2.5 years vs NR, HR=3.9, p=0.0168) and PFS (1.4 vs 4.5 years, HR=4.2, p=0.0005). Midline involvement (brainstem, basal ganglia, thalamus, cerebellum or corpus callosum) also significantly reduced both OS (2.4 vs 12.8 years, HR=7.0, p=0.0014) and PFS (1.4 vs 4.5 years, HR=4.8, p=0.0002). MGMT promoter hypermethylation showed a trend toward significance for PFS (p=0.082) but did not impact OS. Age, sex, tumor size, ATRX immunohistochemistry and tumor-treating field therapy did not impact survival outcomes. Multivariable analyses revealed that PFS remained significantly impacted by both CDKN2A/B homozygous deletion (HR=3.5, p=0.0051) and midline involvement (HR=3.1, p=0.0125). A significant association between CDKN2A/B homozygous deletion and midline involvement was unexpectedly observed (53% if midline, 24% if non-midline; χ2=4.3, p=0.037). Exploratory analyses revealed that 15/15 (100%) of patients with midline involvement demonstrated aberration in RB1 signaling (CDKN2A/B homozygous deletion, n=8; CDKN2A/B hemizygous deletion or loss of heterozygosity, n=6; CDK4 amplification, n=1). CONCLUSION CDKN2A/B homozygous deletion and midline involvement independently impact PFS in patients with grade 4 IDH-mutant astrocytoma treated with standard radiation/temozolomide. Furthermore, midline involvement may be associated with aberrant RB1 signaling.

Impact of surgical intervention on overall survival in malignant pleural mesothelioma: A population-based cohort study with propensity score matching

BackgroundMalignant pleural mesothelioma (MPM) is a rare and aggressive cancer with limited treatment options. This study aims to assess the impact of surgical intervention on overall survival (OS) in patients with MPM and to identify prognostic factors influencing survival outcomes. MethodsData from the SEER-17 Database between 2000 and 2019 were analyzed. Patients were categorized into surgery and no-surgery groups. Survival analyses were conducted using Kaplan-Meier curves and Cox proportional hazards models. Propensity score matching (PSM) was applied to reduce biases. ResultsThe study included a total of 3901 MPM patients, with 1190 in the surgery group and 2711 in the no-surgery group. The median OS for the entire cohort was 10 months. The surgery group had a median OS of 15 months compared to 8 months in the no-surgery group (p < 0.001). The 1-year and 5-year OS rates for surgery patients were 56.9% and 11.2%, respectively, while for no-surgery patients, they were 34.9% and 3.7% (p < 0.001). Multivariate analysis indicated that no-surgery was an independent risk factor for worse OS (HR 1.38, 95% CI 1.21-1.39, p < 0.001). After PSM, no-surgery remained an independent risk factor influencing OS. Subgroup analysis indicated that surgery benefited most groups except those aged ≥80 years, bilateral disease, N3 stage, and certain histological grades. ConclusionSurgical intervention significantly improves survival in patients with MPM. However, benefits vary across subgroups, and careful consideration of patient-specific factors is essential.

Colon Cancer With Bladder Invasion: A Single Center Experience.

The aim of our study was to investigate the outcome of colon cancer with bladder invasion after surgical intervention. Between 2011 and 2022, a total of 41 patients diagnosed with colon cancer and bladder invasion underwent surgical procedures at Taichung Veterans General Hospital. The impact of various risk factors on overall survival (OS) was assessed using Kaplan-Meier analyses and Cox proportional hazards models. Among the enrolled patients, 21 underwent radical cystectomy, while 20 underwent partial cystectomy. Twelve had tumors located in the rectum, 19 in the sigmoid colon, and 10 in both the rectum and sigmoid colon. The median OS was 71.8 months in stage 2, 50.8 months in stage 3, and 11.2 months in stage 4 (p=0.061). Median OS was 71.8 months in patients with negative surgical margins and 10.5 months in those with positive surgical margins (p=0.003). In multivariate regression analysis, positive surgical margins [hazard ratio (HR)=3.64, 95% confidence interval (CI)=1.28-10.34, p=0.015] and emergency operations (HR=4.57, 95%CI=1.34-15.55, p=0.015) significantly impacted OS. Complete resection of colon cancer with bladder invasion can yield excellent oncologic outcomes. The decision between partial and radical cystectomy should balance surgical margin clearance and the preservation of quality of life. Both surgical margin involvement and emergency operations are independent risk factors for OS.

Augmenting Prognostication: Utilizing Activity Trackers to Enhance Survival Prediction in Metastatic Non-Small Cell Lung Cancer

Introduction/BackgroundPrognostication by Performance Status (PS) assessment is a fundamental element of treatment decisions and clinical trial design in oncology, but it is limited by subjectivity and potential miscommunication between patient, physician, and family. Activity tracker offers the potential to collect a broad range of patient-generated data to supplement the assessment of PS. Patients and MethodsPatients with metastatic NSCLC (mNSCLC) participated in a single institute, prospective, observational feasibility study conducted at Huntsman Cancer Institute. Patients were given a Fitbit® activity tracker, which collects their steps taken, distance moved, heart rate, and activity intensity. At baseline, PS was assessed by physicians and patients, and demographics and clinical data were collected. We defined novel indices of health: Heart rate Activity zone Mismatch (HAM) and excessive Sedentary Heart Rate (eSHR). We used multivariable Cox proportional hazards models adjusted for age, sex, and treatment line to estimate and test the prognostic ability of clinical and fitness metrics on overall survival (OS). Each prognostic model was evaluated using Harrell's concordance index (C-index). ResultsFifty-five patients with mNSCLC were enrolled. The median OS was 10.4 months (95% CI: 7.2, 15.2). PS-physician (HR=2.0; p<0.001) and Fitbit® metrics were associated with OS, including daily total steps (1,000-steps) (HR=0.8; p=0.004), HAM (HR=2; p=0.02), eSHR (HR=0.3; p=0.001). The prognostic model that includes PS-physician was associated with the best concordance (C-index=0.75), followed by daily total distance (C-index=0.74) and steps (C-index=0.73) ConclusionsTracker-based measures were prognostic of survival in mNSCLC and may be useful as a supplement or alternative to PS in practice and clinical trials. Micro AbstractPerformance status (PS) is the foundation for clinical trial eligibility and the basis for treatment decisions in thoracic oncology, but it is limited by subjectivity and potential miscommunication between patient, physician, and family. Activity trackers offer a collection of a broad range of patient-generated data that can be used to supplement PS in clinical trials and practice while minimizing subjectivity.

Modeling Overall Survival in Patients With Pancreatic Cancer From a Pooled Analysis of Phase II Trials.

We evaluated the validity of surrogacy of progression-free survival (PFS) or time-to-progression (TTP) and overall response rate (ORR) in phase II trials of pancreatic ductal adenocarcinoma (PDAC). In addition, we explored the impact of predictive variables on overall survival (OS) and developed an optimal OS model. We analyzed 1867 clinical endpoint from 619 phase II PDAC trials with a systematic search from PubMed. Endpoint correlations were determined by Spearman's rank correlation. The assessed predictive factors included PFS/TTP, treatment size, therapy type, stage, and previous treatment. The relationship between predictors and OS was explored by a gamma generalized linear model (GLM) with a log-link function and compared with linear models. The Spearman rank correlation coefficient between PFS/TTP and OS was 0.88 (95% confidence interval [CI] 0.85-0.89; p < 0.0001; n = 610) and between ORR and OS was 0.58 (0.52-0.64; p < 0.0001; n = 514). Model comparison favored the GLM model over the linear model, offering more accurate predictions for higher OS values. Consequently, PFS/TTP was the strongest predictor (pseudo-R2 = 0.75), with 1 added median PFS/TTP month associated with 13% (95% CI 13%-14%) increase in median OS. Subgroup analysis revealed that chemotherapy conferred significantly longer OS compared to targeted therapy in 1-Agent and 2-Agent trials, exhibiting a "very large" and "medium" effect size, respectively (rank biserial, rrb = 0.40 [95% CI 0.22-0.56] and rrb = 0.29 [0.16-0.41], both p < 0.0001), although inconsistent efficacy in 3-Agent trials (rrb = 0.12 [-0.07-0.30], p = 0.21). PFS/TTP is a more reliable surrogate than ORR and a strong predictor of OS in phase II trials of pancreatic cancer. Moreover, gamma GLM (log-link function) is a robust tool for modeling positively skewed survival data with non-constant variance, thus can be applied to other cancers' OS data of such nature.

Positive Lymph Node Ratio as a new prognostic score in Geriatric patients with operated gastric cancer

ObjectiveThe pivotal prognostic determinant for recurrence and survival in surgically treated gastric cancer (GC) patients remains the lymph node status. Despite the adoption of D2 lymph node dissection as the standard approach in recent years, its association with increased morbidity in elderly patients raises concerns. This study aims to explore the prognostic significance of the Positive Lymph Node Ratio (PLNR) score in the context of recurrence and survival among elderly patients with surgically treated GC. Material and methodA retrospective review of files about surgically treated patients with GC was conducted. The prognostic impact of the PLNR score on overall survival (OS) was assessed through Receiver Operating Characteristic (ROC) analysis. ResultsThe cut-off value for the PLNR, determined through ROC analysis, was identified as 0.138. This value serves as a crucial threshold, as it distinguishes patients with a higher risk of poor outcomes. Patients with a PLNR score of 0.138 or below exhibited a median OS of 111 months, whereas those with a PLNR score above 0.138 had a significantly lower median OS of 22 months (p = 0.004). ConclusionOur findings revealed that the PLNR emerged as an independent predictor of survival and recurrence in patients undergoing GC resection.However, it's important to note that while valuable, the PLNR system has limitations. It does not encompass the T stage, a key factor in cancer staging. Therefore, it cannot be a direct substitute for the comprehensive information TNM staging provides. It should be used as a supplementary tool in predicting prognosis, particularly in elderly patients unsuitable for standard lymph node dissection.

The prognostic role of pan-immune inflammation value in patients with metastatic castration resistance prostate cancer treated with Lutetium-177 (177Lu)-PSMA-617.

Pan-immune inflammation value (PIV) is a newly defined biomarker that includes whole cellular components that are indicators of systemic inflammation in complete blood count (CBC), easily accessible and has the potential to reflect both the body's immune response and systemic inflammation status. This study evaluated the pretreatment PIV for its prognostic impact on overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with Lutetium-177 (177Lu)-PSMA-617. The PIV was based on the earliest CBC obtained within 1 month before treatment initiation. Patients were categorized into low and high PIV groups based on the median pretreatment PIV, and the relationship between OS and PIV groups was assessed by multivariable analysis. A total of 43 patients with mCRPC treated with (177Lu)-PSMA-617 were included. The median OS was longer in the low PIV group (15.1 months [95% confidence interval [CI] 10.6-19.5]) than in the high PIV group (4.2 months [95% CI 1.7-6.6]) (p < 0.001). In multivariable analysis, high PIV (hazard ratio [HR]: 4.3, 95% CI 1.194-15.93, p = 0.026) and high Eastern Cooperative Oncology Group performance score (HR: 7.05, 95% CI 1.48-33.46, p = 0.014) were associated with shorter OS. This study showed that pretreatment PIV might be a prognostic factor in patients with mCRPC treated with (177Lu)-PSMA-617.

Shape matters: unsupervised exploration of IDH-wildtype glioma imaging survival predictors

Abstract Objectives This study examines clustering based on shape radiomic features and tumor volume to identify IDH-wildtype glioma phenotypes and assess their impact on overall survival (OS). Materials and methods This retrospective study included 436 consecutive patients diagnosed with IDH-wt glioma who underwent preoperative MR imaging. Alongside the total tumor volume, nine distinct shape radiomic features were extracted using the PyRadiomics framework. Different imaging phenotypes were identified using partition around medoids (PAM) clustering on the training dataset (348/436). The prognostic efficacy of these phenotypes in predicting OS was evaluated on the test dataset (88/436). External validation was performed using the public UCSF glioma dataset (n = 397). A decision-tree algorithm was employed to determine the relevance of features associated with cluster affiliation. Results PAM clustering identified two clusters in the training dataset: Cluster 1 (n = 233) had a higher proportion of patients with higher sphericity and elongation, while Cluster 2 (n = 115) had a higher proportion of patients with higher maximum 3D diameter, surface area, axis lengths, and tumor volume (p &lt; 0.001 for each). OS differed significantly between clusters: Cluster 1 showed a median OS of 23.8 compared to 11.4 months of Cluster 2 in the holdout test dataset (p = 0.002). Multivariate Cox regression showed improved performance with cluster affiliation over clinical data alone (C index 0.67 vs 0.59, p = 0.003). Cluster-based models outperformed the models with tumor volume alone (evidence ratio: 5.16–5.37). Conclusion Data-driven clustering reveals imaging phenotypes, highlighting the improved prognostic power of combining shape-radiomics with tumor volume, thereby outperforming predictions based on tumor volume alone in high-grade glioma survival outcomes. Clinical relevance statement Shape-radiomics and volume-based cluster analyses of preoperative MRI scans can reveal imaging phenotypes that improve the prediction of OS in patients with IDH-wild type gliomas, outperforming currently known models based on tumor size alone or clinical parameters. Key Points Shape radiomics and tumor volume clustering in IDH-wildtype gliomas are investigated for enhanced prognostic accuracy. Two distinct phenotypic clusters were identified with different median OSs. Integrating shape radiomics and volume-based clustering enhances OS prediction in IDH-wildtype glioma patients.

Genetic risk stratification and outcomes among treatment-naive patients with AML treated with venetoclax and azacitidine

AbstractThe European LeukemiaNet (ELN) acute myeloid leukemia (AML) genetic risk classification systems are based on response to intensive chemotherapy; their ability to discriminate outcomes in older patients treated with venetoclax-azacitidine may be suboptimal. This pooled analysis of the phase 3 VIALE-A trial (NCT02993523) and phase 1b study (NCT02203773) examined prognostic stratification according to the 2017 and 2022 ELN risk classifications and derived new molecular signatures differentiating venetoclax-azacitidine–treated patients based on overall survival (OS). Overall, 279 patients treated with venetoclax-azacitidine and 113 patients treated with placebo-azacitidine were analyzed. The ELN 2017 or 2022 prognostic criteria classified most patients as adverse-risk AML (60.2% and 72.8% for venetoclax-azacitidine and 65.5% and 75.2% for placebo-azacitidine, respectively). Although outcomes with venetoclax-azacitidine improved across all ELN risk groups compared with placebo-azacitidine, ELN classification systems poorly discriminated venetoclax-azacitidine outcomes. By applying a bioinformatic algorithm, new molecular signatures were derived differentiating OS outcomes with venetoclax-azacitidine. The mutational status of TP53, FLT3 internal tandem duplication (FLT3-ITD), NRAS, and KRAS categorized patients into higher-, intermediate-, and lower-benefit groups (52%, 25%, and 23% of patients, respectively), each associated with a distinct median OS (26.5 months [95% confidence interval (CI), 20.2-32.7]; 12.1 months [95% CI, 7.3-15.2]; and 5.5 months [95% CI, 2.8-7.6], respectively). ELN prognostic classifiers did not provide clinically meaningful risk stratification of OS outcomes in patients treated with venetoclax-azacitidine. TP53, FLT3-ITD, NRAS, and KRAS mutation status allows the classification of these patients into 3 risk groups with distinct differences in median OS. These trials were registered at www.clinicaltrials.gov as #NCT02993523 and #NCT02203773.

Oncologic outcomes of neoadjuvant chemotherapy and lymph node dissection with partial cystectomy for muscle-invasive bladder cancer.

Partial cystectomy (PC) offers potential benefits for select patients with muscle-invasive bladder cancer (MIBC). However, the oncologic efficacy of PC may be compromised due to the underutilization of standard-of-care modalities, such as neoadjuvant chemotherapy (NAC) and pelvic lymph node dissection (PLND). We aimed to assess factors influencing the incorporation of NAC and PLND with PC and evaluate their impact on overall survival (OS). We identified 2,832 patients with cT2-4N0M0 bladder cancer (BCa) who underwent PC between 2004 and 2019 using the National Cancer Database (NCDB). The primary endpoint was OS. Kaplan-Meier analysis compared OS in treatment modalities in PC patients. Multivariate Cox Proportional Hazards (CPH) model assessed the impact of age, sex, race, insurance, income, Charlson-Deyo Index (CDI), clinical T-stage, facility type, histology, surgical margins, NAC, PLND adequacy [≥10 lymph node (LN) yield], and adjuvant radiation treatment on OS. Multivariate logistic regressions were performed to examine predictors of NAC and PLND receipt in PC patients. Two hundred and thirty-one patients received multi-agent NAC with PC. NAC treatment with PLND was associated with significantly improved OS (P<0.001). Median OS was 43.9 months in patients treated with PC alone, while median OS was not reached in PC patients treated with NAC & PLND. Furthermore, patients who received NAC without any PLND had a median OS of 50.6 months, while those treated with PLND without NAC had a median OS of 76.5 months. This persisted in the adjusted CPH model, where private insurance, NAC, and PLND significantly improved OS, especially when PLND yielded ≥10 LN. Conversely, age >80 years old, CDI >2, cT3-4, positive margins, and adjuvant radiation all increased adjusted mortality risk. After controlling for clinicopathologic variables, females were less likely to receive PLND [odds ratio (OR) 0.719, P=0.005], while NAC was more likely administered to PC patients diagnosed from 2016-2019 (OR 5.295, P<0.001). PC patients who received NAC were more likely to have PLND performed as part of their treatment regimen (OR 2.189, P<0.001). Additionally, patients treated at academic centers were more likely to have NAC administered and PLND performed (OR 1.745, P=0.003; OR 2.465, P<0.001, respectively). Despite guideline recommendations, the utilization of NAC and PLND with PC remains insufficient. Our analysis underscores the significant OS benefit of these recommended treatments as part of MIBC care. Importantly, we highlight a gradual increase in NAC and PLND receipt in recent years, centered largely at academic facilities. Notably, gender disparities exist in PLND receipt, emphasizing the need for further investigation.

Impact of primary tumor resection in the management of metastatic well-differentiated neuroendocrine tumors of the small bowel and pancreas.

Patients with gastroenteropancreatic (GEP) neuroendocrine tumors (NET) often present with advanced disease. Primary tumor resection (PTR) in the setting of unresectable metastatic disease is controversial. Most studies evaluating the impact of PTR on overall survival (OS) have been performed using large population-based databases, with limited treatment related data. This study aims to determine whether PTR improves OS and progression-free survival (PFS) in patients with metastatic well-differentiated GEP-NET. This is a retrospective single-institution study of patients with metastatic well-differentiated GEP-NET between 1978 and 2021. The primary outcome was OS. The secondary outcome was PFS. Chi-squared tests and Cox regression were used to perform univariate and multivariate analyses (MVA). OS and PFS were estimated using the Kaplan-Meier method and log-rank test. Between 1978 and 2021, 505 patients presented with metastatic NET, 151 of whom had well-differentiated GEP-NET. PTR was performed in 31 PNET and 77 SBNET patients. PTR was associated with improved median OS for PNET (136 vs. 61 months, p = .003) and SBNET (not reached vs. 79 months, p<.001). On MVA, only higher grade (HR 3.70, 95%CI 1.49-9.17) and PTR (HR 0.21, 95%CI 0.08-0.53) influenced OS. PTR resulted in longer median PFS for patients with SBNET (46 vs. 28 months, p = .03) and a trend toward longer median PFS for patients with PNET (20 vs. 13 months, p = .07). In patients with metastatic well-differentiated GEP-NET, PTR is associated with improved OS and may be associated with improved PFS and should be considered in a multidisciplinary setting. Future prospective studies are needed to validate these findings.

Early tumor shrinkage as a prognostic predictor in chemotherapy-naïve patients with locally advanced pancreatic cancer treated with modified FOLFIRINOX or gemcitabine plus nab-paclitaxel combination therapy: An exploratory analysis of JCOG1407

BackgroundEarly tumor shrinkage (ETS) is a prognostic predictor for patients treated with chemotherapy in colorectal cancer, although scarce studies evaluated its potential in locally advanced pancreatic cancer (LAPC). In this exploratory analysis of JCOG1407, a randomized phase II study comparing modified 5-fluorouracil, levofolinate, irinotecan, and oxaliplatin (mFOLFIRINOX) and gemcitabine plus nab-paclitaxel (GnP), we evaluated whether ETS can predict prognosis of patients with LAPC. MethodsOf the 126 patients enrolled in JCOG1407, 112 with measurable lesions were included in this study. ETS was defined as a ≥20 % reduction in tumor diameter compared with baseline at the initial imaging assessment 6–10 weeks after initiating chemotherapy. Patients were divided into the ETS (achieved ETS) and non-ETS (failed to achieve ETS) groups based on their ETS status. The impact of ETS on overall survival (OS) was compared using multivariable Cox regression analysis. ResultsFourteen of 55 (25.5 %) and 24 of 57 (42.1 %) patients in the mFOLFIRINOX and GnP arms, respectively, achieved ETS. In the overall population, mFOLFIRINOX arm, and GnP arm, the median OS in the ETS and non-ETS groups was 27.1 and 20.4, 29.8 and 20.6, and 24.1 and 20.4, months, respectively. The adjusted hazard ratios of OS for the ETS group in the overall population, mFOLFIRINOX arm, and GnP arm were 0.451 (95 % confidence interval [CI]: 0.270–0.754), 0.371 (95 % CI: 0.149–0.926), and 0.508 (95 % CI: 0.255–1.004), respectively. ConclusionsETS may be a prognostic predictor in chemotherapy-naïve patients with LAPC treated with mFOLFIRINOX or GnP.

Impact of homologous recombination repair/BReast CAncer (BRCA) gene alterations on survival in a real-world setting of metastatic prostate cancer.

To investigate alterations of homologous recombination repair (HRR) and especially BReast CAncer 1/2 (BRCA1/2) gene on overall survival (OS). Moreover, to explore the effect of inhibition of poly(ADP-ribose)-polymerase (PARPi) as systemic therapy for metastatic castration-resistant prostate cancer (mCRPC). Of all HRR-screened patients with metastatic prostate cancer, baseline characteristics were sampled. Kaplan-Meier estimates and multivariable Cox regression models predicted the effect of HRR/BRCA1/2 alterations on OS. Of 196 eligible patients, 61 (31%) harboured any HRR and 40 (20%) BRCA1/2 alterations. Of HRR alterations, 40 (66%) vs six (10%) vs five (8.2%) vs four (6.6%) vs two (3.3%) vs four (6.6%) were BRCA1/2 vs Ataxia-telangiectasia mutated kinase (ATM) vs checkpoint kinase 2 (CHEK2) vs cyclin-dependent kinase 12 (CDK12) vs Fanconi anaemia complementation Group A (FANCA) vs positive for other mutations. Of these, 30% received a PARPi. OS differed significantly between HRR-positive vs -negative patients. Specifically in hormone-sensitive prostate cancer, the median OS was 63 (HRR positive) vs 57 (BRCA1/2 positive) vs 113 months (HRR negative) (P ≤ 0.01). In mCRPC, OS was 42 (HRR positive) vs 41 (BRCA1/2 positive) vs 70 months (HRR negative) (P ≤ 0.01). HRR and BRCA1/2 alterations were associated with worse OS after multivariable adjustment. Finally, patients with mCRPC with BRCA1/2 mutation treated without PARPi harboured worse OS than patients with BRCA1/2 mutation and PARPi therapy (median OS: 33 vs 48 months, P < 0.03). Incidence of HRR alteration in a clinical real-world setting is high when using blood- and tissue-based tests. Patients with HRR/BRCA alterations have worse outcomes resulting in significant OS differences between HRR/BRCA-positive patients with mCRPC with and without PARPi usage vs HRR/BRCA-negative patients.

The Impact of Local Control on Overall Survival after Y-90 Selective Internal Radiotherapy of Liver Metastases in Oligometastatic Cancer: A Retrospective Analysis.

Y-90 Selective Internal Radiotherapy (SIRT) is an ablative therapy used for inoperable liver metastasis. The purpose of this investigation was to examine the impact of local control after SIRT on overall survival (OS) in oligometastatic patients. A retrospective, single-institution study identified oligometastatic patients with ≤5 non-intracranial metastases receiving unilateral or bilateral lobar Y-90 SIRT from 2009 to 2021. The primary endpoint was OS defined from Y-90 SIRT completion to the date of death or last follow-up. Local failure was classified as a progressive disease at the target lesion(s) by RECIST v1.1 criteria starting at 3 months after SIRT. With a median follow-up of 15.7 months, 33 patients were identified who had a total of 79 oligometastatic lesions treated with SIRT, with the majority histology of colorectal adenocarcinoma (n = 22). In total, 94% of patients completed the Y-90 lobectomy. Of the 79 individual lesions treated, 22 (27.8%) failed. Thirteen patients received salvage liver-directed therapy following intrahepatic failure; ten received repeat SIRT. Median OS (mOS) was 20.1 months, and 12-month OS was 68.2%. Intralesional failure was associated with worse 1 y OS (52.3% vs. 86.2%, p = 0.004). These results suggest that intralesional failure following Y-90 may be associated with inferior OS, emphasizing the importance of disease control in low-metastatic-burden patients.

Non-surgical pancreatic cancer: The role of radiotherapy in prolonging survival, A retrospective cohort study in the SEER database.

Limited research has compared external beam radiotherapy (RT) to non-RT in patients with non-surgical locally advanced pancreatic cancer (LAPC). Therefore, this study investigates the impact of RT on overall survival (OS) in patients with non-surgical LAPC in a real-world context. We conducted an analysis of patients with non-surgical LAPC using data from the Surveillance, Epidemiology, and End Results (SEER) database. This analysis involved the utilization of Kaplan-Meier survival curves and multivariable Cox regression analyses. A total of 5,413 individuals with non-surgical LAPC were included in this analysis. Among them, 2,320 (42.9%) received RT, while 3,093 (57.1%) underwent non-RT treatment. The median OS was 12.0 months for the RT group and 9.0 months for the non-RT group, with a statistically significant difference (P<0.001). Multivariate analysis revealed that RT had a statistically significant impact on OS (HR, 0.86; 95% CI, 0.81-0.91; P<0.001). Propensity score matching (PSM) analysis confirmed a statistically significant association of RT with improved OS (HR, 0.84, 95% CI, 0.79-0.90; P<0.001). These results remained consistent after conducting sensitivity analyses, subgroup analyses, and PSM. The study findings suggest that RT could be advantageous for patients with non-surgical LAPC. Further investigations are warranted to explore the relationship between RT and OS.

DIPG-52. CEREBROSPINAL FLUID DIVERSION DOES NOT PROLONG OVERALL SURVIVAL IN CHILDREN WITH DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG): A REPORT FROM THE INTERNATIONAL DIPG REGISTRY

Abstract BACKGROUND The role of permanent cerebrospinal fluid (CSF) diversion in the management of patients with diffuse intrinsic pontine glioma (DIPG) is poorly elucidated. There are no standard practice guidelines regarding the role of these neurosurgical interventions in patients with DIPG or large studies regarding the impact of CSF diversion on overall survival (OS) or palliation in this disease. METHODS Data were extracted from subjects registered in the International DIPG registry (IDIPGR). Univariable analyses were performed using the Fisher’s exact test or Wilcoxon rank sum test. Survival was estimated using the Kaplan-Meier method. RESULTS Of n=1104 evaluable patients with DIPG registered in the IDIPGR, n=303 (27.4%) had permanent CSF diversion. Median time from diagnosis to CSF diversion was 1 month (range 0-4 months). There were no significant differences in age, gender or race in subjects with CSF diversion versus no CSF diversion. Patients with CSF diversion had a higher incidence of hydrocephalus at diagnosis (64.1% vs 11.3%, p&amp;lt;0.001). There was no significant difference in OS or post-progression survival (PPS) at 1,2 and 3 years between subjects with permanent CSF diversion compared to those without (p=0.5 and p=0.8, respectively). Median OS was 11 months in both. Median PPS was 7 months (no CSF diversion) and 6 months (CSF diversion). Patients reported less headache and vomiting after permanent CSF diversion compared to pre-diversion (p&amp;lt;0.0001), however steroid use was also significantly higher after CSF diversion (p&amp;lt;0.001). CONCLUSIONS In this, the largest reported international cohort of patients with DIPG with permanent CSF diversion, we show that permanent CSF diversion was not associated with an improvement in OS or PPS. CSF diversion improved headache and vomiting but was also associated with increased rates of steroid use. This highlights the need for consensus guidelines regarding the use of these diversion strategies in patients with DIPG.

Should new organ involvement be included in Response Evaluation Criteria in PSMA Imaging?

The current study is intended to investigate the effect of new organ involvement on overall survival (OS) and modify the Response Evaluation Criteria in PSMA Imaging (RECIP) by including new organ involvement to RECIP 1.0. This retrospective study includes 114 patients diagnosed with metastatic castration-resistant prostate cancer (mCRPC) between September 2017 and June 2022 who had received docetaxel treatment and had baseline and post-treatment prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) images. The inclusion criteria were patients with pre- and post-treatment [18F]FDG PET/CT images and whose [18F]FDG PET images were negative. Those whose data were unavailable, who had additional malignancy, or who received abiraterone, enzalutamide, or Lutetium (Lu)-177 treatment were excluded. Age, Gleason score (GS), TPSA (total prostate-specific antigen) levels, surgical history, and OS information were recorded for each patient. The 114 patients herein had a median age of 72.5 (51-91) years and a median GS of 8 (7-10). New lesions were observed in 59 patients (51.7%) and new organ PSMA uptake was observed in 14 patients (12.2%). In the multivariate Cox regression analysis, volume-based treatment response (vTR)-total lesion PSMA (TLP), RECIP PSMA-VOL, modified RECIP (mRECIP) PSMA-VOL, and mRECIP TLP were independent prognostic factors for mortality (p < 0.001, p = 0.006, p = 0.003, and p = 0.003, respectively). The median OS of patients with new organ involvement and new lesion with PSMA uptake was 9.3months (95% CI 2.1-16.5months) and 11.8months (95% CI 7.4-16.2months), respectively. The study concluded that new organ involvement had a shorter OS than new lesion involvement. In the mRECIP that we developed, unlike RECIP, we demonstrated that both PSMA-VOL and TLP value were independent prognostic factors for mortality.

Overall survival following heterogeneous FDG-guided dose-escalation for locally advanced NSCLC in the international phase III NARLAL2 trial.

LBA8069 Background: The survival and loco-regional control for patients (pts) with locally advanced non-small cell lung cancer (LA_NSCLC) treated with radiotherapy (RT) are dismal despite adjuvant Durvalumab. However, there have been concerns about dose escalation for these pts since the unexpected result of the dose-escalation trial RTOG0617. A novel approach is therefore warranted to escalate the dose to the tumor. A possible approach is to use the principle from stereotactic body radiotherapy (SBRT) with inhomogeneous dose distribution. SBRT has demonstrated excellent local control in early-stage lung cancer. The international multicenter NARLAL2 (novel approach to RT for LA_NSCLC) phase III trial on dose escalation, randomized pts with LA_NSCLC between standard 66 Gy/ 33 fractions (F) versus heterogeneous FDG-PET driven dose escalation, aiming at mean dose to GTV-tumorPET 95 Gy/ 33 F and mean dose to GTV-nodePET 74 Gy/ 33 F while strictly respecting dose to organs at risk. We here present the data on overall survival (OS) 1 year after the end of recruitment. Methods: Pts aged ≥18 years with LA_NSCLC were recruited from seven institutions in Denmark and Norway. Eligibility criteria included ECOG PS 0-1, histological or cytological confirmed NSCLC stage IIB-IIIB, signed informed consent, and a clinically acceptable plan for RT with conventional 66 Gy/ 33 F. PET-CT and brain MR were part of staging. Pts were randomly assigned to either treatment group (1:1, stratified for center and histology). The trial aimed to have iso-lung toxicity within the treatment arms by creating two RT plans (before randomization) for each patient (one for each treatment arm) with matching mean lung dose and lung V20Gy. The follow-up (FU) were scheduled weekly during RT, every 3rd month for 2 years, and every 6th month for another 3 years after randomization. At FU visit a CT-scan and toxicity scoring were performed. All interim analyses were passed without interventions (toxicity and OS). The trial's primary endpoint was time to loco-regional failure from randomization. Secondary endpoints included OS, acute, and late toxicity. The sample size calculations requested 350 pts to be enrolled in the study. Recruitment of the pre-planned number of pts finalized in March 2023. The trial was registered with ClinicalTrials.gov (NCT02354274). Results: From January 2015 to March 2023, 350 pts were randomized: 177 and 173 pts in standard and escalated arms respectively. The two groups were well-balanced regarding age, gender, stage, and PS. The dose to GTV-tumor was 66.5 Gy [66.2, 67.1] (median [IQR]) in the standard arm and 88.1 Gy [84.9, 90.4] in the escalated arm. Median OS were 35.8 months (m) and 51.6 m for pts treated in the standard and escalated arm, respectively ( p = 0.36). Median FU time 50.8 m (reverse Kaplan-Meier). Conclusions: Dose escalation is safe in the NARLAL2 setting with respect to OS. Clinical trial information: NCT02354274 .

Association of ephrinB2 (B2) expression on overall survival (OS) and resistance to PD1/L1 inhibitors (inh) in metastatic urothelial carcinoma (mUC).

4577 Background: B2 is a ligand for EphB4 (B4) which enhances tumor invasion, proliferation, survival and promotes angiogenesis. TCGA data (N= 409) bladder cancer patients (pts) showed B2 high expression (34%) had poor OS vs. low expression (66%) (Hazard Ratio- HR- 0.7 p=0.02). Our phase II trial of sEphB4-HSA, a B2 inhibitor, combined with pembrolizumab in pre-treated mUC (N=70) showed an objective response rate (ORR) of 37%. Pts with high B2 had 52% ORR with 24% complete response (CR) (JCO PMID 35984996). This retrospective study examined the OS and ORR to PD1/L1 inh in pts with mUC and its correlation with B2 expression. Methods: Pts with mUC who received PD1/L1 inh were eligible if they had radiographic response data and tumor tissue for B2 testing. Demographics and disease characteristics were abstracted. Radiographic was assessed using RECIST 1.1. Tumor specimens were analyzed for B2 expression using in-situ hybridization (ISH). Scores of 2-4 were marked High (Hi) and 0-1 Low (Lo). Descriptive statistics summarized the results. Cox Model, logrank and Fisher’s exact test were used for the association of B2 status with OS and ORR, respectively, using SAS 9.4. Results: 143 (N) pts from University of Southern California (USC, n = 49), Dana Farber (DFCI, n = 55), and University of California, Irvine (UCI, n = 39) were included. 101 pts were male (71%). Median age was 73. PD1/L1 inh included pembrolizumab (n = 111, 78%), atezolizumab (n = 25, 17%), nivolumab, avelumab, and durvalumab in 3%, 1%, and 1%, respectively. ORR defined as CR + partial response (PR) was 21% (95% CI 14%, 29%) (N = 136 evaluable). ORR was 12% vs 33% in B2 Hi vs Lo, p = 0.005. The median OS was 17.2 months (mo) (95% CI 13.5, 23.8) (N = 143). Median OS was 14.5 (95% CI 9.4, 21.0) mo vs 24.0 (95% CI 13.7, 60.8) mo for B2 Hi vs Lo, logrank p = 0.022 (HR 1.65 95% CI:1.07, 2.55 Wald p = 0.023). Conclusions: B2 Hi is associated with poor OS and poor ORR in PD1/L1 inh monotherapy treated mUC acting as a biomarker of disease outcome. These data suggest B2-B4 pathway to be a mechanism of resistance to PD1/L1 inh and a therapeutic target. [Table: see text]