Overall Survival Estimates Research Articles

Long-term outcomes following proton therapy for pediatric spinal low-grade glioma.

Due to its rarity, no standard treatment guidelines exist for pediatric spinal low-grade glioma (LGG-S). Proton therapy (PT) offers an attractive modality to minimize toxicity. Herein, we present the first published series of pediatric patients who received PT for progressive LGG-S. We identified eight consecutive patients with nonmetastatic LGG-S treated with PT. Cumulative incidence method was used to estimate local control (LC), freedom from distant metastases (FFDM), and freedom from progression (FFP). The Kaplan-Meier product limit method assessed overall survival (OS). Toxicity was assessed according to the Common Terminology Criteria for Adverse Events Version 5.0. Median age at diagnosis was 4 years. All patients underwent attempted resection and developed recurrence/progression prior to referral for PT, with median duration between initial surgery and PT of 4.4 years. Median age at the start of PT was 8 years. Most patients (n=5) received PT as ≥third line treatment. Seven patients were treated with PT to the primary tumor. Most patients (n=7) received between 45-50.4 CGE. Median follow up was 7.8 years. The 10-year estimates for LC, FFDM, FFP, and OS were 85, 88, 73, and 55%, respectively. One patient experienced malignant transformation and two developed pseudoprogression following PT. No pulmonary, gastrointestinal, or musculoskeletal toxicities were observed during or after PT. Despite negative selection bias our experience suggests PT for pediatric LGG-S offers long-term disease control with limited toxicity. The favorable therapeutic ratio of PT suggests it should be considered among first-line therapy in children with nonmetastatic, unresectable LGG-S.

Consensus molecular subtyping of metastatic colorectal cancer expands biomarker-directed therapeutic benefit for patients with CMS1 and CMS2 tumors.

We developed a whole transcriptome sequencing (WTS)-based Consensus Molecular Subtypes (CMS) classifier using FFPE tissue and investigated its prognostic and predictive utility in a large clinico-genomic database of CRC patients (n = 24,939). The classifier was trained against the original CMS datasets using an SVM model and validated in an independent blinded TCGA dataset (88.0% accuracy). Kaplan-Meier estimates of overall survival (OS) and time-on-treatment (TOT) were calculated for each CMS (p < 0.05 considered significant). CMS2 tumors were enriched on left-side of colon and conferred the longest median OS. In RAS-wildtype mCRC, left-sided tumors and CMS2 classification were associated with longer TOT with anti-EGFR antibodies (cetuximab and panitumumab). When restricting to only CMS2, there was no significant difference in TOT between right- versus left-sided tumors. CMS1 tumors were associated with a longer median TOT with pembrolizumab relative to other CMS groups, even when analyzing only microsatellite stable (MSS) tumors. A WTS-based CMS classifier allowed investigation of a large multi-institutional clinico-genomic mCRC cohort, suggesting anti-EGFR therapy benefit for right-sided RAS-WT CMS2 tumors and immune checkpoint inhibitor benefit for MSS CMS1. Routine CMS classification of CRC provides important treatment associations that should be further investigated.

Craniospinal irradiation and/or intraventricular radioimmunotherapy after high-dose chemotherapy and autologous stem cell rescue in patients with CNS retinoblastoma-Safety and outcomes.

The prognosis for patients with central nervous system (CNS) retinoblastoma (RB) (trilateral or stage 4b metastatic RB) treated with high-dose chemotherapy and autologous stem cell transplant (HDC-ASCT) remains poor. The impact of irradiation when administered as part of upfront therapy post HDC-ASCT on treatment outcomes and survival is unknown. We performed a retrospective review of all patients with CNS RB (seven stage 4b, eight trilateral, one pineal lesion belonging to methylation group RB) who underwent induction chemotherapy with an intent to proceed to HDC-ASCT at two institutions. Twelve of 16 patients (n=75%) achieved an objective response to induction chemotherapy, while four patients had progressive/refractory disease; two patients responded to subsequent therapy and proceeded to ASCT, and two patients did not. Seven of 14 patients who underwent HDC-ASCT, received radiotherapy as part of upfront therapy post HDC-ASCT in the form of craniospinal irradiation (CSI) (n=3), intraventricular radioimmunotherapy (n=3), or both CSI and intraventricular radioimmunotherapy (n=1). The Kaplan-Meier estimate of overall survival for these patients was 62.5% at 5years; no patients developed second malignant neoplasms within the radiation fields. For the seven patients who did not receive radiotherapy, the overall survival was 28.6% at 5years. CSI (23.4Gy) alone or in conjunction with intraventricular RIT may have clinical utility in eliminating persistent MRD post HDC-ASCT, contributing to improved disease-free survival in patients with CNS RB. This treatment strategy merits evaluation in a prospective, multicenter clinical trial for patients with CNS metastatic RB.

Disease-specific survival outcomes for patients after locoregional treatment for ductal carcinoma in situ: observational cohort study.

Breast-conserving surgery alone, breast-conserving surgery with adjuvant radiation treatment, and mastectomy are guideline-concordant treatments for ductal carcinoma in situ. The aim of this study was to compare survival outcomes between these treatment options. A stratified random sample of patients diagnosed with pure ductal carcinoma in situ between 2008 and 2014 was selected from 1330 sites in the USA. Data on diagnosis, treatment, and follow-up were abstracted by local cancer registrars. Population-averaged marginal estimates of disease-specific survival and overall survival for breast-conserving surgery alone, breast-conserving surgery with radiation treatment, and mastectomy were obtained by combining sampling and overlap weights. A total of 18 442 women were included, with a median follow-up of 67.8 (interquartile range 46.1-93.5) months. A total of 35 women died from breast cancer, at a median age of 62 (interquartile range 50-74) years. Population-averaged 8-year rates of disease-specific survival were 99.6% or higher for all treatment groups, with no significant differences between groups (breast-conserving surgery alone versus breast-conserving surgery with radiation treatment, HR 1.19 (95% c.i. 0.29 to 4.85); and mastectomy versus breast-conserving surgery with radiation treatment, HR 1.74 (95% c.i. 0.53 to 5.72). There was no difference in overall survival between the patients who underwent a mastectomy and the patients who underwent breast-conserving surgery with radiation treatment (HR 1.09 (95% c.i. 0.83 to 1.43)). Patients who underwent breast-conserving surgery alone had lower overall survival compared with the patients who underwent breast-conserving surgery with radiation treatment (HR 1.29 (95% c.i. 1.00 to 1.67)). This survival difference vanished for all but one subgroup, namely patients less than 65 years (HR 1.86 (95% c.i. 1.15 to 3.00)). There was no statistically significant difference in disease-specific survival between women operated with breast-conserving surgery alone, breast-conserving surgery with radiation treatment, or mastectomy for ductal carcinoma in situ. Given the low absolute risk of disease-specific mortality, these results provide confidence in offering individualized locoregional treatment without fear of compromising survival.

Prognostic factors in patients with intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) is the second commonly-seen liver malignancy and one of the most fatal cancers in Taiwan. Survival after diagnosis of ICC remains poor. This study aimed to investigate the survival and prognostic factors in patients with ICC. All patients with newly diagnosed ICC during 2004 to 2018 were identified from a national cancer database and followed until December 2020. Estimates of overall survival (OS) were conducted using the Kaplan–Meier method and Cox proportional hazards model. Hazard ratios with 95% confidence intervals were calculated. Initially, 7940 patients with ICC disease (stage IV: 55.6%, 4418/7940) were eligible for this study. Only 32.3% (2563/7940) patients with ICC underwent liver resection. After Propensity score matching, 969 pairs (N = 1938) of patients were matched and selected (mean age 62.8 ± 11.0 years, 53.1% were male, 29.7% had cirrhosis). The median follow-up time was 80.0 months (range 25–201 months). The 3-, 5-year OS rates were 44.0%, 36.4% in the surgical group and 26.0%, 23.7% in the non-surgical group, respectively. Surgery, young patients (≤ 54 years), small tumor size, no vascular invasion and chemotherapy were associated with better OS in patients with stages I–III disease. Surgery benefit was maximum in stage I disease followed by stage II. In patients with stage IV disease, factors such as surgery, young patients (≤ 64 years), single tumor, and no vascular invasion were associated with better OS. Chemotherapy was insignificantly associated with better OS. Long-term survival in patients with ICC is very poor. Compared to non-surgical patients, surgery conveys approximately 18% and 12% better OS rates at 3-year and 5-year, respectively. Early detection and surgical intervention may improve OS substantially in patients with ICC.

Paraneoplastic Syndrome Prevalence and Survival in Racially-Diverse Cohort With Renal Cell Carcinoma

IntroductionThe prevalence of preoperative paraneoplastic syndromes (PNS) in renal cell carcinoma (RCC) is poorly understood. Many laboratory abnormalities representative of PNS have demonstrated prognostic value when incorporated into predictive survival models in RCC. We sought to characterize the relationship between baseline prevalence of PNS with overall survival (OS) and cancer-specific survival (CSS) in RCC patients following nephrectomy. MethodsOur prospectively maintained nephrectomy database was retrospectively reviewed for any stage, major histology RCC patients that underwent surgery from 2000 to 2022. Baseline laboratory values within 90 days (closest used) were required. Presence of PNS was defined according to established laboratory cutoffs. Kaplan-Meier curves estimated survival rates, and multivariable Cox proportional hazards models examined the association between PNS with OS and CSS following nephrectomy. Results2599 patients were included with listed staging: 1494 Stage I; 180 Stage II; 616 Stage III; 306 Stage IV. Proportion of patients presenting with >1 PNS significantly increased from stage I (31.3%) to stage IV (74.2%) RCC (P < .001). Elevated C-reactive protein was the most prevalent PNS (45.4%). On multivariable analysis, the presence of >1 PNS was associated with higher risk of all-cause (HR 2.09; P < .001) and cancer-specific mortality (HR 2.55; P < .001). The 10-year OS estimates as reported: 65.2% (no PNS), 52.3% (1 PNS), 36.6% (>1 PNS); and 10-year CSS estimates: 88.3% (no PNS), 79.3% (1 PNS), 61.6% (>1 PNS). DiscussionIncreased prevalence of PNS in major histology RCC was associated with a significant increase in the risk of all-cause and cancer-specific mortality even when accounting for patient and disease characteristics.

Bitter taste receptors as prognostic markers in adrenocortical carcinoma.

230 Background: Adrenocortical carcinoma (ACC) is a rare malignant neoplasm of the adrenal gland. Progressive forms of this cancer carry a dismal prognosis with 5-year survival rates &lt; 40%. As such, predictors of stage progression and prognostic biomarkers are a must. Taste 2 receptors (TAS2Rs) are localized on the surface of bitter receptor cells. Recent evidence has shown their role as prognostic biomarkers in multiple cancers, such as breast, prostate, and head and neck squamous cell carcinoma. The aim of this study was to elucidate the role of TAS2Rs in ACC. Methods: Differentially expressed genes (DEGs) based on high and low expression groups of TAS2R genes were identified through the 'DESeq2' package on R. Subsequent Gene Set Enrichment Analysis (GSEA) was performed using the 'TCGAbiolinks' package on R and Enrichr online tool. Immune infiltration analysis was conducted using TIMER2.0 and CIBERSORT. Survival analysis with an optimal expression cutoff for overall survival (OS) and a median cutoff for disease-free survival (DFS) based on The Cancer Genome Atlas Adrenocortical carcinoma (TCGA-ACC) data was executed using the 'survival' and 'survminer' R packages and GEPIA2 online tool. Results: Analysis of the TCGA-ACC cohort revealed OS estimates that indicated worse survival in patients with higher TAS2R14, TAS2R19, TAS2R20, and TAS2R30 expression (Table). Further analysis produced consistent results, demonstrating that elevated expressions of TAS2R14 and TAS2R19 are correlated with decreased DFS, with Hazard Ratios (HR) of 2.60 (p = 0.0046) and 2.20 (p = 0.022), respectively. Furthermore, the F-test and stage plots have shown consistent upregulation of selected TAS2R genes across stages I–IV (p &lt; 0.05). RNA-seq analysis revealed 1170 common (579 downregulated, 591 upregulated) DEGs between high and low TAS2R14 and TAS2R19 expression groups. GSEA showed upregulated genes in high expressers have relations to hedgehog signaling, epithelial to mesenchymal transition, TGF-B signaling, and organization of the extracellular matrix. On the other hand, down-regulated genes showed functions in metabolic reprogramming, chemokine receptor binding, MHC protein complex, and chemokine-mediated inflammation. GSEA on co-expressed genes showed pathways related to ferroptosis, autolysosome activity, and iron homeostasis and metabolism. Immune infiltration analysis revealed significantly increased CD4+, naïve and plasma B cell infiltration with higher TAS2R14 and TAS2R19 expression (Rho &gt; 0.25, p &lt; 0.05), in addition to increased M1 macrophage infiltration with higher TAS2R19 expression (Rho = 0.28, p &lt; 0.05). Conclusions: TAS2R genes are potentially involved in modulating carcinogenic processes, including stage progression, metastasis and invasion, immune regulation, and metabolic processes. This modulation may explain the poorer prognostic outcomes in ACC patients with elevated TAS2R expression. Further validation in external cohorts is necessary to confirm these results. [Table: see text]

46 Radiological tumor burden is an independent risk factor for survival in patients with metastatic clear cell renal cell carcinoma (mccRCC) treated with first line immunotherapy (IO)-based regimens

Abstract Background IO-based regimens (IO + IO or IO + VEGF inhibitor) represent current standard of care systemic therapies for the management of patients with mRCC. IMDC is the current standard to assess prognosis in patients with mRCC of clear cell histology. Baseline radiological tumor burden (BRTB) is a readily available measurement to calculate using routine CT-scans. Here we describe the utility of BRTB as prognostic factor in patients with mccRCC treated with first line IO-based regimens. Methods We reviewed data of 183 patients with mccRCC treated at Dana-Farber Cancer Institute from August 2014 to October 2023 and who received ≥ 1 dose of an IO-based regimen (IO + IO or IO + VEGF inhibitor). Patients with available CT-scan reports within 1 month prior to first line treatment initiation were included in our analysis. BRTB was assessed by a single operator as the sum of all measurable lesions as listed on the RECIST v1.1 report. The primary outcome was overall survival (OS), and secondary outcomes were time to treatment failure (TTF) and time to next therapy (TTNT). To evaluate the impact of BRTB on OS, TTF and TTNT, we used univariable and multivariable Cox regression models accounting for IMDC risk group, history of nephrectomy, and presence of either bone, liver, or brain metastases prior to first line initiation. Results A total of 150 patients satisfied the inclusion criteria and were included in our final analysis, of which 80% of patients were male (120/150). 9% (13/150) had favorable risk, 51% (77/150) had intermediate risk and 20% (30/150) had poor risk by IMDC criteria. Overall, 73% (109/150) of patients had nephrectomy prior to first line therapy initiation and 41% (61/150) had either brain, bone, or liver metastasis. Median follow-up was 44.8 months. Every 1 cm increase in BRTB was associated with a 5% increase in risk of death (HR: 1.05; 95% CI: 1.03 – 1.08; p &amp;lt; 0.0001). On multivariable analysis, radiological tumor burden was significantly associated with OS (HR: 1.04; 95%CI: 1.00 – 1.08; p = 0.03). After categorizing BRTB by tertiles, tertile 1 included 0 - 7.5 cm, tertile 2: 7.6– 15.3 cm and tertile 3: 15.4 – 47.7 cm. The 4-year OS estimates were 84% (95%CI: 74 – 97%), 60% (95%CI: 45 – 81%) and 43% (95%CI: 29 – 66%), respectively, for the 1st, 2nd and 3rd tertile (log-rank P &amp;lt; 0.0001). BRTB did not show a significant association with TTF on univariable (HR: 1.00; 95%CI: 0.99 – 1.01; p = 0.783), or multivariable analysis (HR: 0.99; 95%CI: 0.97 – 1.01; p = 0.428). As for TTNT, BRTB also did not show a significant association on univariable (HR: 1.01; 95%CI: 1.0 – 1.02; p = 0.234) or multivariable analysis (HR: 1.01; 95%CI: 0.99 – 1.03; p = 0.453). Conclusions Baseline radiological tumor burden is an independent prognostic factor for OS in patients with mccRCC treated with first line immunotherapy-based regimens. However, tumor burden is not significantly associated with TTF or TTNT. Figure: Kaplan-Meier curves representing OS based on baseline radiological tumor burden assessed by RECIST v1.1 (Tertile 1: 0 - 7.5 cm; Tertile 2: 7.6 - 15.3 cm; Tertile 3: 15.4 – 47.7 cm). P value is derived from the log-rank test.

Novel machine-learning prediction tools for overall survival of patients with chondrosarcoma: Based on recursive partitioning analysis.

Chondrosarcoma (CHS), a bone malignancy, poses a significant challenge due to its heterogeneous nature and resistance to conventional treatments. There is a clear need for advanced prognostic instruments that can integrate multiple prognostic factors to deliver personalized survival predictions for individual patients. This study aimed to develop a novel prediction tool based on recursive partitioning analysis (RPA) to improve the estimation of overall survival for patients with CHS. Data from the Surveillance, Epidemiology, and End Results (SEER) database were analyzed, including demographic, clinical, and treatment details of patients diagnosed between 2000 and 2018. Using C5.0 algorithm, decision trees were created to predict survival probabilities at 12, 24, 60, and 120 months. The performance of the models was assessed through confusion scatter plot, accuracy rate, receiver operator characteristic (ROC) curve, and area under ROC curve (AUC). The study identified tumor histology, surgery, age, visceral (brain/liver/lung) metastasis, chemotherapy, tumor grade, and sex as critical predictors. Decision trees revealed distinct patterns for survival prediction at each time point. The models showed high accuracy (82.40%-89.09% in training group, and 82.16%-88.74% in test group) and discriminatory power (AUC: 0.806-0.894 in training group, and 0.808-0.882 in test group) in both training and testing datasets. An interactive web-based shiny APP (URL: https://yangxg1209.shinyapps.io/chondrosarcoma_survival_prediction/) was developed, simplifying the survival prediction process for clinicians. This study successfully employed RPA to develop a user-friendly tool for personalized survival predictions in CHS. The decision tree models demonstrated robust predictive capabilities, with the interactive application facilitating clinical decision-making. Future prospective studies are recommended to validate these findings and further refine the predictive model.

Temporal evolution of living donor liver transplantation survival—A United Network for Organ Sharing registry study

Living donor liver transplantation (LDLT) is a curative treatment for various liver diseases, reducing waitlist times and associated mortality. We aimed to assess the overall survival (OS), identify predictors for mortality, and analyze differences in risk factors over time. Adult patients undergoing LDLT were selected from the United Network for Organ Sharing database from inception (1987) to 2023. The Kaplan-Meier method was used for analysis, and multivariable Cox proportional hazard models were conducted. In total, 7257 LDLT recipients with a median age of 54 years (interquartile range [IQR]: 45-61 years), 54% male, 80% non-Hispanic White, body mass index of 26.3 kg/m2 (IQR: 23.2-30.0 kg/m2), and model for end-stage liver disease score of 15 (IQR: 11-19) were included. The median cold ischemic time was 1.6 hours (IQR: 1.0-2.3 hours) with 88% right lobe grafts. The follow-up was 4.0 years (IQR: 1.0-9.2 years). The contemporary reached median OS was 17.0 years (95% CI: 16.1, 18.1 years), with the following OS estimates: 1 year 95%; 3 years 89%; 5 years 84%; 10 years 72%; 15 years 56%; and 20 years 43%. Nine independent factors associated with mortality were identified, with an independent improved OS in the recent time era (adjusted hazards ratio: 0.53; 95% CI: 0.39, 0.71). The median center-caseload per year was 5 (IQR: 2-10), with observed center-specific improvement of OS. LDLT is a safe procedure with excellent OS. Its efficacy has improved despite an increase of risk parameters, suggesting its limits are yet to be met.

Clinicogenomic predictors of survival and intracranial progression after stereotactic radiosurgery for colorectal cancer brain metastases.

Brain metastases (BM) from colorectal cancer (CRC) are associated with dismal prognosis. When BM-directed therapy is considered, better methods are needed to identify patients at risk of poor oncological outcomes in order to optimize patient selection for closer surveillance or escalated therapy. The authors sought to identify clinicogenomic predictors of survival and intracranial disease progression after CRC BM have been treated with stereotactic radiosurgery (SRS). Patients with newly diagnosed CRC BM treated with SRS between 2009 and 2022 who had next-generation genomic sequencing data available were included. Frameless SRS was delivered in 1-5 fractions, alone or after neurosurgical resection. Outcomes included overall survival (OS) and intracranial progression (IP), evaluated per patient treated with SRS, and local progression (LP), evaluated per BM. Associations between baseline clinicogenomic features and outcomes were evaluated with Cox regression and competing risk regression, with death as a competing risk. This analysis included 123 patients with 299 BM. At BM diagnosis, 111 patients (90%) had progressive extracranial disease, and 79 patients (64%) had ≥ 3 sites of extracranial metastasis. The median (IQR) number of BM was 2 (1-3) per patient. The median (IQR) biologically effective dose (BED) was 51.3 (51.3-65.1) Gy, corresponding to a prescription of 27 Gy in 3 fractions. OS, IP, and LP estimates at 1 year after SRS were 36%, 55%, and 12%, respectively. OS was independently associated with progressive extracranial disease (HR 4.26, 95% CI 1.63-11.2, p = 0.003) and ≥ 3 extracranial metastatic sites (HR 1.84, 95% CI 1.12-3.01, p = 0.02). LP was less likely when BM received BED ≥ 51.3 Gy (HR 0.24, 95% CI 0.07-0.78, p = 0.02), independent of BM diameter (HR 1.21/cm, 95% CI 0.8-1.84, p = 0.4). IP was independently associated with genomic alterations; TP53 driver alterations were associated with higher risk of IP (HR 2.71, 95% CI 1.26-5.79, p = 0.01), whereas MYC pathway alterations were associated with lower risk (HR 0.15, 95% CI 0.03-0.68, p = 0.01). The authors identified clinicogenomic features associated with adverse outcomes after SRS for CRC BM. Progressive and extensive extracranial metastases predicted worse OS. Insufficient SRS doses predicted greater risk of LP. Wild-type TP53 and alterations in the MYC pathway were independently associated with lower risk of IP. Patients at high risk of IP may be considered for closer surveillance or escalated therapy.

Real-World Experience With Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer in Canada. However, few real-world reports exist on the treatment of refractory locally advanced (LA) and metastatic cSCC with cemiplimab to date. The objective of this study was to characterize the demographic and clinical outcomes of advanced cSCC patients on cemiplimab in a real-world setting. Retrospective analysis of adult patients with refractory LA and metastatic cSCC treated with cemiplimab at the London Regional Cancer Program in Canada. Patient demographics and treatment characteristics were reported, as well as Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS). Forty patients were included in this study. Sixteen (40%) had LA disease and 24 (60%) had metastatic disease. Median treatment duration was 3.5 months (range: 0.6-29.4 months). Kaplan-Meier analyses of the entire study population revealed that the median OS was not reached [NR; 95% confidence interval (CI) 9.1 months-NR], but median PFS was 11.5 months (95% CI 7.0 months-NR). A total of 25% of patients experienced at least one adverse event from cemiplimab. Reasons for treatment discontinuation were death from any cause (25%), disease progression (15%), cemiplimab adverse events (5%), and other causes (15%). The 12 month estimates of OS and PFS were lower than pivotal phase I and II clinical trials. However, toxicity was tolerable. Cemiplimab remains a safe and effective therapy in patients with refractory LA and metastatic cSCC disease.

Survival and prognostic factors of primary retroperitoneal sarcomas after surgery: a single-center experience.

The percentage of retroperitoneal sarcomas (RPS) among all soft tissue sarcomas ranges from 10 to 15%. Surgery remains the gold standard for RPS. In this study, we analyzed the impact of surgical treatment for primary RPS on recurrence and overall mortality at a Chinese institution and identified and evaluated prognostic variables. Data from patients with RPS who underwent surgical treatment were retrospectively analyzed. The patients were treated at a single center from January 2000 to June 2018. Retrospectively collected demographic, clinicopathological, and surgical factors were examined. Overall survival (OS) and disease-free survival (DSF) were used as the primary endpoints. Predicted 5-year survival rates, encompassing both DFS and OS, were derived from the Sarculator prognostic nomogram. A total of 110 patients met the inclusion criteria. The median follow-up time after surgery for patients with primary RPS was 5.3 years. During this period, 59 patients died. The 5-year OS and DFS estimates were 63.5% and 35.3%, respectively. In a multivariate analysis, poor OS following surgical treatment of primary RPS was independently correlated with FNCLCC grade (p < 0.001) and surgical margin status (p = 0.016). FNCLCC grade (p = 0.001) and surgical margin status (p = 0.002) were also independently associated with poor DFS. The C-indices for 5-year OS and DFS survival utilizing the Sarculator prognostic nomogram were 0.71 and 0.73 respectively. The overall mortality rate of patients with RPS was considered acceptable. OS and DFS prognostic markers were established for primary RPS. Tumor grade and intraregional margins are other factors that affect survival and recurrence.

Effect of Medicaid expansion on cancer treatment and survival among Medicaid beneficiaries and the uninsured.

The Affordable Care Act expanded Medicaid coverage for people with low income in the United States. Expanded insurance coverage could promote more timely access to cancer treatment, which could improve overall survival (OS), yet the long-term effects of Medicaid expansion (ME) remain unknown. We evaluated whether ME was associated with improved timely treatment initiation (TTI) and 3-year OS among patients with breast, cervical, colon, and lung cancers who were affected by the policy. Medicaid-insured or uninsured patients aged 40-64 with stage I-III breast, cervical, colon, or non-small cell lung cancer within the National Cancer Database (NCDB). A difference-in-differences (DID) approach was used to compare changes in TTI (within 60 days) and 3-year OS between patients in ME states versus nonexpansion (NE) states before (2010-2013) and after (2015-2018) ME. Adjusted DID estimates for TTI and 3-year OS were calculated using multivariable linear regression and Cox proportional hazards regression models, respectively. ME was associated with a relative increase in TTI within 60 days for breast (DID = 4.6; p < 0.001), cervical (DID = 5.0 p = 0.013), and colon (DID = 4.0, p = 0.008), but not lung cancer (p = 0.505). In Cox regression analysis, ME was associated with improved 3-year OS for breast (DID hazard ratio [HR] = 0.82, p = 0.009), cervical (DID-HR = 0.81, p = 0.048), and lung (DID-HR = 0.87, p = 0.003). Changes in 3-year OS for colon cancer were not statistically different between ME and NE states (DID-HR, 0.77; p = 0.075). Findings suggest that expanded insurance coverage can improve treatment and survival outcomes among low income and uninsured patients with cancer. As the debate surrounding ME continues nationwide, our findings serve as valuable insights to inform the development of policies aimed at fostering accessible and affordable healthcare for all.

Pleomorphic Xanthoastrocytoma: Multi-Institutional Evaluation of Stereotactic Radiosurgery

BACKGROUND AND OBJECTIVES: Pleomorphic xanthoastrocytoma (PXA) is a rare low-grade glial tumor primarily affecting young individuals. Surgery is the primary treatment option; however, managing residual/recurrent tumors remains uncertain. This international multi-institutional study retrospectively assessed the use of stereotactic radiosurgery (SRS) for PXA. METHODS: A total of 36 PXA patients (53 tumors) treated at 11 institutions between 1996 and 2023 were analyzed. Data included demographics, clinical variables, SRS parameters, tumor control, and clinical outcomes. Kaplan-Meier estimates summarized the local control (LC), progression-free survival, and overall survival (OS). Secondary end points addressed adverse radiation effects and the risk of malignant transformation. Cox regression analysis was used. RESULTS: A total of 38 tumors were grade 2, and 15 tumors were grade 3. Nine patients underwent initial gross total resection, and 10 received adjuvant therapy. The main reason for SRS was residual tumors (41.5%). The median follow-up was 34 months (range, 2-324 months). LC was achieved in 77.4% of tumors, with 6-month, 1-year, and 2-year LC estimates at 86.7%, 82.3%, and 77.8%, respectively. Younger age at SRS (hazard ratios [HR] 3.164), absence of peritumoral edema (HR 4.685), and higher marginal dose (HR 6.190) were significantly associated with better LC. OS estimates at 1, 2, and 5 years were 86%, 74%, and 49.3%, respectively, with a median OS of 44 months. Four patients died due to disease progression. Radiological adverse radiation effects included edema (n = 8) and hemorrhagic change (n = 1). One grade 3 PXA transformed into glioblastoma 13 months after SRS. CONCLUSION: SRS offers promising outcomes for PXA management, providing effective LC, reasonable progression-free survival, and minimal adverse events.

Clinical Outcomes for BRCA Pathogenic Variant Carriers With Breast Cancer Undergoing Breast Conservation

Although most women with BRCA-associated breast cancer choose bilateral mastectomy, current guidelines support breast-conserving therapy as an option. As the indications for genetic testing expand and targeted therapies emerge, understanding the outcomes of breast-conserving therapy in the population of patients choosing breast conservation is important. To describe the clinical outcomes of women with BRCA-associated breast cancer who were treated with breast-conserving therapy, including the risks of ipsilateral and contralateral cancer events and bilateral mastectomy-free survival. This cohort study conducted at a single-institution academic national comprehensive cancer center included 172 women identified from a prospectively maintained database who had pathogenic BRCA1/2 variants and were treated with breast-conserving therapy from January 1, 1977, to December 31, 2021. Clinical and pathologic characteristics for patients with BRCA1 and BRCA2 were compared, and estimates of overall survival, bilateral mastectomy-free survival, distant disease-free survival, risk of ipsilateral breast cancer, and risk of contralateral cancer were computed. The cohort included 172 women (mean [SD] age, 47.1 [11.7] years), with 42 (24.4%) receiving a diagnosis of breast cancer prior to 40 years of age. Compared with BRCA2 variant carriers (80 [46.5%]), women with BRCA1 variants (92 [53.5%]) were younger at breast cancer diagnosis and tended to have more advanced tumors, which were more likely to be hormone receptor negative and higher grade. At a median follow-up of 11.8 years (IQR, 5.7-18.2 years), estimates of 10-year survival and risk were: overall survival, 88.5% (95% CI, 83.1%-94.2%); bilateral mastectomy-free survival, 70.7% (95% CI, 63.3%-78.9%); risk of an ipsilateral breast cancer event, 12.2% (95% CI, 5.8%-18.2%); and risk of contralateral cancer, 21.3% (95% CI, 13.3%-28.6%). Risks continued to increase after 10 years of follow-up. In this cohort study, although women with breast cancer and pathogenic BRCA1/2 variants treated with breast-conserving therapy had above-average risks of ipsilateral and contralateral breast cancer events, most did not have another cancer event and remained bilateral mastectomy free. These findings may be useful for informing patients with BRCA variants choosing breast conservation.

Long-term outcomes following proton therapy for non-metastatic central nervous system germinoma in children and adolescents

Background/PurposeRadiation is a key component in the treatment of central nervous system pure germinoma (PG) in children and adolescents. Proton therapy (PT) improves normal tissue sparing and potentially reduces adverse effects (AE). The aim of this study was to present the largest single institution experience utilizing PT for the management of PG. Materials MethodsWe enrolled 35 non-metastatic patients with PG that were treated with PT at our institution between July 2007 – September 2021. Most received induction chemotherapy (n = 31, 89 %) and whole ventricular irradiation with an involved field boost (n = 29, 83 %). The most common total dose was 30 CGE (n = 18, 51.4 %). We utilized the cumulative incidence method to estimate local control (LC), freedom from distant metastases (FFDM), freedom from progression (FFP), and overall survival (OS). Treatment related toxicity was assessed per CTCAE version 5. ResultsMedian follow-up was 6.2 years (range, 0.9–––15.2). The 10-year Kaplan-Meier estimates for LC, FFDM, FFP, and OS were 100 %, 100 %, 100 %, and 94 % respectively. The most common AE were hearing impairment requiring hearing aids (n = 3), transient hypersomnia requiring medication (n = 3), and new onset endocrinopathy (n = 1). Of the 23 evaluable patients ≥ 18 years old at last follow-up, 8 were high school graduates/in college, 8 college graduates, and 7 others gainfully employed. ConclusionsWhen utilized in modern multimodality treatment of non-metastatic PG, the precise dosimetry of PT does not compromise disease control. Although serious radiation side effects are rare, the 100% cure rate supports further investigation into selective radiation dose and volume de-escalation.

A phase II trial of UGT1A1 genotype-guided FOLFIRI plus bevacizumab as first-line therapy for advanced, unresectable colorectal cancer.

FOLFIRI is a standard regimen for metastatic colorectal cancer (mCRC). We hypothesized that a pharmacogenomic-directed strategy where more efficient irinotecan metabolizers (UGT1A1 *1/*1 homozygotes and *1/*28 heterozygotes) receive higher-than-standard irinotecan doses would improve progression-free survival (PFS) compared to non-genotype selected historical controls with acceptable toxicity. In this phase II multicenter study irinotecan dosing in first-line FOLFIRI and bevacizumab for mCRC was based on UGT1A1 genotype with *1/*1, *1/*28, and *28/*28 patients receiving 310 mg/m2, 260 mg/m2, and 180 mg/m2, respectively. Primary endpoint was PFS. Secondary endpoints were investigator and patient-reported adverse events, and estimation of overall survival (OS). One-hundred patients were enrolled with 91 evaluable for PFS and 83 evaluable for best response. Median PFS was 12.5 months (90% CI 10.9, 15.4), shorter than the anticipated alternative hypothesis of 14 months. PFS by genotype was 12.5 months (90% CI 10.9, 17.4) for *1/*1, 14.6 months (90% CI 11.8, 17.5) for *1/*28, and 6 months (90% CI 2.3, 7.7) for *28/28, respectively. OS was 24.5 months (90% CI 19.1, 30.7) and by genotype was 26.5 (90% CI 19.1, 32.9), 25.9 (90% CI 17.6, 37.7), and 13.4 (90% CI 2.3, 20.5) months for *1/*1, *1/*28, and *28/*28, respectively. G3/4 toxicity was similar between all subgroups, including diarrhea and neutropenia. A pharmacogenomic-directed irinotecan strategy improved PFS in the *1/*1 and *1/*28 genotypes with higher rates of neutropenia and similar rates of diarrhea compared to expected with standard FOLFIRI dosing. However, improvements in response rate and PFS were modest. This strategy should not change standard practice for mCRC patients in the first-line setting.

Second Allogeneic Hematopoietic Cell Transplantation for Relapsed Adult Acute Myeloid Leukemia: Outcomes and Prognostic Factors

Second allogeneic hematopoietic cell transplantation (HCT2) is potentially curative for adults with acute myeloid leukemia (AML) or myelodysplastic neoplasm (MDS)/AML experiencing relapse after a first allograft (HCT1), but prognostic factors for outcomes are poorly characterized. To provide a detailed analysis of HCT2 outcomes and associated prognostic factors in a large single-center cohort, with a focus on identifying predictors of relapse and nonrelapse mortality (NRM), we studied adults ≥18 years who underwent HCT2 at a single institution between April 2006 and June 2022 for relapsed AML (n = 73) or MDS/AML (n = 8). With a median follow-up among survivors of 74.0 (range: 10.4 to 187.3) months, there were 30 relapses and 57 deaths, of which 29 were NRM events, contributing to the estimates for relapse, overall survival (OS), relapse-free survival (RFS), and NRM. Three-year estimates for relapse, RFS, and OS were 37% (95% confidence interval: 27% to 48%), 32% (23% to 44%), and 35% (26% to 47%). The rate of NRM at 100 days and 18 months was 20% (12% to 29%) and 28% (19% to 39%). Outcomes differed markedly across patient subsets and were substantially worse for patients who underwent HCT2 with active disease (ie, morphologic evidence of bone marrow and/or extramedullary disease), for patients who relapsed ≤6 months after HCT1, and for patients with higher HCT-specific Comorbidity Index (HCT-CI) or treatment-related mortality (TRM) scores. After multivariable adjustment, active disease was associated with a higher risk of relapse (hazard ratio [HR] = 3.19, P = .006) and shorter RFS (HR = 2.41, P = .008) as well as OS (HR = 2.17, P = .027) compared to transplant in morphologic remission without multiparameter flow cytometric evidence of measurable residual disease. Similarly, a relapse-free interval ≤6 months after the first allograft was associated with higher risk of relapse (HR = 5.86, P < .001) and shorter RFS (HR = 2.86; P = .001) and OS (HR = 2.45, P = .003). Additionally, a high HCT-CI score was associated with increased NRM (HR = 4.30, P = .035), and shorter RFS (HR = 3.87, P = .003) and OS (HR = 3.74, P = .006). Likewise, higher TRM scores were associated with increased risk of relapse (HR = 2.27; P = .024) and NRM (HR = 2.01, P = .001), and inferior RFS (HR = 1.90 P = .001) and OS (HR = 1.88, P = .001). A significant subset of patients with AML or MDS/AML relapse after HCT1 are alive and leukemia-free 3 years after undergoing HCT2. Our study identifies active leukemia at the time of HCT2 and early relapse after HCT1 as major adverse prognostic factors, highlighting patient subsets in particular need of novel therapeutic approaches, and supports the use of the HCT-CI and TRM scores for outcome prognostication.

Partitioned overall survival: Comprehensive analysis of survival states over 4 years in CheckMate 9ER comparing first-line nivolumab plus cabozantinib versus sunitinib in advanced renal cell carcinoma (aRCC).

4507 Background: Immunotherapy regimens can be associated with prolonged disease control after treatment discontinuation without the need for further anticancer therapy. An integrated, comprehensive partitioned survival analysis describes how patients spend overall survival (OS) time, on/off treatment, with/without toxicity. Previous analysis of first-line (1L) nivolumab (NIVO) + ipilimumab (IPI) for aRCC in CheckMate 214 showed treatment-free survival (TFS) twice as long vs sunitinib (SUN). TFS and survival states for immune checkpoint inhibitor plus tyrosine kinase inhibitor (TKI) combination are of interest. Methods: Overall, 651 patients (pts) with aRCC were randomized to receive 1L NIVO + cabozantinib (CABO) or SUN in the CheckMate 9ER trial; treatment continued until progression or intolerance, NIVO for at most 24 months. Minimum follow-up was 4 years. We partitioned area under the Kaplan–Meier (KM) OS curve into 3 survival states, defined from randomization: time on 1L protocol therapy, TFS, and survival after subsequent systemic therapy (second line [2L]) initiation. TFS and protocol therapy were subdivided as mean times with/without reported grade 2+ treatment-related adverse events (TRAEs). Areas under and between KM curves were estimated by 48-month restricted mean times to event. Bootstrapped 95% CIs for between-group differences are reported. Results: At 4 years post randomization, KM estimates of OS were 49.2% vs 40.2% of pts assigned to NIVO+CABO vs SUN, respectively; 17.6% vs 4.7% of pts were surviving treatment-free, and 15.8% vs 8.2% were continuing on 1L protocol therapy. Over the 48-month period since randomization (Table), the mean TFS (95% CI) was 2.4 (0.8–3.9) months longer after treatment with NIVO+CABO than SUN. At least half of TFS was spent with toxicity in both treatment groups, resulting in difference in mean TFS (95% CI) without toxicity of 0.7 (−0.4 to 1.8) month. The NIVO+CABO group spent a mean (95% CI) of 8.5 (6.2–10.8) months more survival time on 1L protocol therapy, whereas the SUN group spent a mean (95% CI) of 6.5 (4.4–8.6) months more survival time after 2L therapy initiation. Conclusions: Over the 4-year period since initiation of 1L therapy for aRCC, the longer OS achieved with NIVO+CABO was accompanied by 1.5 times longer mean time surviving treatment-free before 2L therapy compared with SUN, a smaller difference than seen for NIVO + IPI vs SUN. [Table: see text]