Significant Difference In On Overall Survival Research Articles

Development and validation of a nomogram integrating marital status for 5-year overall survival of chondrosarcoma: a population-based study.

The objective of this study was to evaluate the influence of marital status on overall survival (OS) and develop a nomogram for predicting 5-year OS in chondrosarcoma (CHS) patients. We utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify CHS patients diagnosed between 2010 and 2018. Survival rates were calculated using Kaplan-Meier analysis. Prognostic factors were identified through univariate and multivariate analyses. An independent cohort was used for external validation of the nomogram. Performance evaluation of the nomogram was conducted using Harrell's concordance index (C-index), calibration plot, and decision curve analysis (DCA). In the SEER cohort, Kaplan-Meier analysis showed significant differences in OS among CHS patients with different marital statuses (P < 0.001), with widowed patients having the lowest OS. In terms of gender, there were significant survival differences based on marital status in females (P < 0.001), but not in males (P = 0.067). The OS of married and single females is significantly higher than that of married (P < 0.001) and single male (P = 0.006), respectively. Kaplan-Meier curves showed no significant difference in OS between groups stratified by either gender or marital status in the external cohort. Univariate and multivariate analyses confirmed that age at diagnosis, gender, marital status, tumor size, histological type, tumor grade, SEER stage, and surgery were independent prognostic factors for OS. The nomogram demonstrated high internal and external validation C-indexes of 0.818 and 0.88, respectively. Calibration plots, DCA curve, and Kaplan-Meier curve (P < 0.001) confirmed the excellent performance and clinical utility of the nomogram. Marital status was an independent factor influencing OS in CHS patients, with widowed patients having the worst prognosis. The OS of both married and single females is significantly higher than that of their male counterparts. However, these findings require further validation in a large independent cohort. While the contribution of marital status on predicting OS appears modest, our nomogram accurately predicted 5-year OS and identified high-risk groups, providing a valuable tool for clinical decision-making.

Abstract PS10-02: Association between Germline Mutation Status and Overall Survival among Women with Breast Cancer in Population-based Studies in the United States

Abstract Background: The influence of germline pathogenic variants (PVs) in breast cancer predisposition genes on overall survival (OS) after breast cancer diagnosis is not well defined, particularly for PVs in genes other than BRCA1 and BRCA2, and in the context of estrogen-receptor (ER) positive breast cancer. Even for BRCA1/2, OS estimates in women with breast cancer have primarily been derived from high-risk women qualifying for genetic testing due to young age at diagnosis or family history of cancer, and OS estimates by germline PV status from population-based studies are lacking. Methods: The study included 16,797 prospectively followed women with locoregional breast cancer within the population-based CARRIERS study who underwent surgical resection of the primary tumor. OS was compared between germline PV carriers and non-carriers (negative for germline PVs in 12 breast cancer predisposition genes) from the time of breast cancer diagnosis in a multivariable Cox proportional hazard regression analysis adjusting for age and menopausal status at diagnosis, race/ethnicity, ER status, type of surgery, use of adjuvant radiation, chemotherapy and endocrine agents, and prophylactic oophorectomy. Further subset analyses by race/ethnicity ER status of the primary tumor and adjusting for relevant covariates were also performed. Results: Germline PVs in ATM, BRCA1, BRCA2, CHEK2, or PALB2 were detected in 5.6% of the women in the study [ATM: 142 (0.8%), BRCA1: 206 (1.2%), BRCA2: 260 (1.5%), CHEK2:167 (1.0%) and PALB2:116 (0.7%)]. Compared to non-carriers, a significant difference in OS was not observed for germline PV carriers in ATM, BRCA1, BRCA2, or CHEK2 in the overall study population. However, a trend towards worse OS was noted for PALB2 PV carriers compared to non-carriers although this was not statistically significant (Hazard Ratio (HR): 1.36, 95%CI: 0.98 – 1.89, p=0.06). Further subset analysis by race/ethnicity demonstrated that the OS was significantly worse among Black PALB2 PV carriers (HR: 3.11, 95%CI: 1.74 – 5.55, p&amp;lt; 0.001) but not in non-Hispanic White PALB2 PV carriers (HR: 1.00, 95%CI: 0.59 – 1.70, p=0.98) compared to non-carriers within the same race/ethnicity. Among 12,780 women with ER+ breast cancer, compared to non-carriers, OS was significantly worse in BRCA2 PV carriers (HR: 1.51, 95%CI: 1.06 – 2.16, p=0.02) and a trend towards worse OS was observed in BRCA1 PV carriers (HR:1.53, 95%CI:0.93 – 2.51, p=0.09). Among women with ER-negative breast cancer, a significant difference in OS was not observed between PV carriers in each of the five genes and non-carriers. Conclusions: The differences in OS by race/ethnicity in PALB2 PV carriers and by ER status of the tumor in BRCA2 PV carriers warrant further investigation of underlying tumor biology and assessment of endocrine sensitivity of breast cancer in germline PV carriers. Citation Format: Fergus Couch. Association between Germline Mutation Status and Overall Survival among Women with Breast Cancer in Population-based Studies in the United States [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS10-02.

Effect of Primary Site and Treatment Modality of Patients With Head and Neck Myoepithelial Carcinoma on Survival

AimEpidemiological evidence on myoepithelial carcinoma is rare. This study aimed to investigate the effect of tumor primary site and treatment modality on survival in patients with head and neck myoepithelial carcinoma. Materials and methodsData on adult patients diagnosed with head and neck myoepithelial carcinoma between 2000 and 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Uni- and multivariable Cox proportional hazard models were utilized to evaluate the effects of different tumor primary sites and treatment modalities on overall survival (OS) and cancer-specific survival (CSS), and expressed as hazard ratio (HR) and 95% confidence interval (CI). ResultsA total of 415 patients were enrolled. No significant differences in OS and CSS were found between different tumor primary sites (P > 0.05). Compared with partial excision, patients with total excision (HR = 1.65, 95%CI: 1.12–2.42) (partial or total removal of the organ in which the tumor is located and complete removal of the tumor) or no surgery (HR = 3.52, 95%CI: 2.05–6.03) had worse OS. Compared with surgery only, patients with radiotherapy only had poorer OS (HR = 4.69, 95%CI: 2.32–9.46) and CSS (HR = 6.72, 95%CI: 2.59–17.46), while no significant differences in OS (P = 0.120) and CSS (P = 0.847) were found among patients who received surgery combined with radiotherapy. In patients with AJCC III/IV, patients with radiotherapy only (HR = 4.51, 95%CI: 1.61–12.62) had poorer OS compared to those with surgery only, whereas patients who received surgery combined with radiotherapy had better OS (HR = 0.50, 95%CI: 0.29–0.89). ConclusionThe tumor primary site may not affect the prognosis of patients with myoepithelial carcinoma, while the effect of treatment modality on prognosis is related to the primary site and stage of the tumor.

Impact of Type of Hypomethylating Agent (HMA) Used on Outcomes of Patients (Pts) with Higher-Risk Myelodysplastic Syndromes/Neoplasms (HR-MDS) - a Large, Multicenter, Retrospective Analysis

JPB and TK Co-first; RK and AMZ are Co-senior authors Introduction HMAs remain the mainstay for frontline treatment of HR-MDS. Azacitidine (AZA) and decitabine (DEC; including oral cedazuridine/decitabine) are the only FDA-approved HMAs. However, AZA and DEC have not been compared directly in randomized trials. In this study, we aimed to assess the clinical outcomes of pts with HR-MDS treated with different HMA regimens, focusing on overall survival (OS) and treatment responses. Methods The VALIDATE database includes pts with HR-MDS treated with HMA-based therapies in the frontline setting from 14 specialized MDS centers. HR-MDS pts treated with HMA-based therapies in the frontline setting were included. HR-MDS was defined as having an IPSS ≥1.5 or IPSS-R &amp;gt;3.5 (n=213 pts excluded). Pts were excluded from the survival analysis if age at diagnosis was &amp;lt;18 years (n=1), bone marrow (BM) blasts ≥20% or unknown at HMA initiation (n=61), or if survival status, follow-up time, date of HMA initiation, or HMA type was unknown (n=28). To be included in the analysis of response based on IWG 2023 criteria (Zeidan A et al, Blood 2023), pts had to have a BM response assessment within 180 days after HMA initiation to allow determination of response (n=290 pts excluded). Time to event analyses were estimated using the Kaplan-Meier method and treatment groups (AZA vs DEC monotherapy) were compared by log-rank test and assessed from the time of HMA initiation. Multivariable Cox regression models were performed among pts treated with AZA and DEC monotherapy to identify predictors of response and OS. This study was supported by an independent research grant from AbbVie. Results 1,223 pts were screened of whom 919 were included in the survival analysis. Median age was 68 years (Range [R]: 19-95) with 66% males. Our cohort was enriched for pts with adverse genetic features including complex karyotype (38%) and TP53 mutations (36%). Overall, 76% of pts were treated with HMA monotherapy (56% AZA, 20% DEC) and 24% received HMA-based combination therapy (HMA/VEN: 15%, other HMA combinations: 9%). 38.2% underwent allogeneic hematopoietic cell transplant (allo-HCT). The median HMA duration was 5 cycles (R: 1 - 94). Due to the small number and the heterogeneity of pts receiving HMA combinations, as well the multiple partner drugs used in these pts ( Table), we compared OS and responses only between pts treated with AZA (n = 512 pts) or DEC monotherapy (n = 186 pts). In unadjusted analyses, median OS differed by treatment type (p = 0.002) and was 19.8 months (mo) with AZA (95% CI: 17.0 - 23.1 mo) and 14.3 mo with DEC (95% CI: 11.2 - 18.5 mo). Among 629 pts evaluable for response, rates of complete remission (CR) and overall response (ORR) were 14.8% and 48.6% for AZA monotherapy and 5.6% and 50.4% for DEC monotherapy, respectively. In a Cox multivariable regression model ( Figure) adjusted for age, sex, TP53 mutation status, complex karyotype, IPSS-M category (compared to very high risk), and receipt of allo-HCT, there was no difference in OS when comparing AZA and DEC monotherapy (Hazard ratio [HR]: 0.95, 95% CI: 0.72 - 1.26; p = 0.740). Variables associated with adverse OS were male sex (HR: 1.52; 95% CI: 1.16 - 2.00; p = 0.002) and presence of TP53 mutation (HR: 1.50, 95% CI: 1.05 - 2.14; p = 0.027). Conversely, receipt of allo-HCT (HR: 0.26, 95% CI: 0.19 - 0.37; p&amp;lt;0.001) and IPSS-M moderate-high (HR: 0.57, 95% CI: 0.37 - 0.87; p=0.009) and moderate-low (HR: 0.58, 95% CI: 0.36 - 0.95; p = 0.031; both compared to IPSS-M very high risk) were associated with improved OS. Similarly, there were no statistically significant differences in ORR between AZA and DEC (OR: 1.05, 95% CI: 0.66 - 1.68; p = 0.832) in a Cox multivariable regression model adjusted for age, sex, TP53 mutation, complex karyotype, IPSS-M category, and treatment type. Conclusions: Among pts included in the real-world VALIDATE database, there were no significant difference in OS or ORR (IWG 2023) between AZA- and DEC-treated pts in adjusted analyses. Other factors (e.g., TP53 mutations, complex karyotype) are substantially more relevant to outcomes than the specific HMA used. The small number of pts and heterogeneity of partner drugs in HMA-based combinations precluded robust analyses or conclusions regarding differences in efficacy. Additional analyses evaluating the impact of combinations and molecular subtypes on response and survival will be presented during the meeting as more pts are added to the database.

Outcomes of Tcrαβ and CD19-Depleted Hematopoietic Stem Cell Transplantation from Matched, Mismatched Unrelated and Haploidentical Donors for Pediatric Patients with Hematological Malignancy: A Meta-Analysis

Introduction: TCR αβ+/CD19+ depletion in hematopoietic stem cell transplantation (HSCT) is an emerging graft manipulation technique to help overcome the HLA barrier in the mismatched or haploidentical transplant setting and reduce or prevent graft-versus-host disease. Limited research has explored the impact of various donor sources, and type of malignancy on the outcomes of TCR αβ+/CD19+ depleted HSCT for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndrome (MDS). Therefore, we performed a comprehensive meta-analysis of published clinical studies using individual patient data (IPD) to address this scientific gap. Methods: This meta-analysis combined patient-level data from studies involving AML/MDS and ALL patients treated with TCR αβ+/CD19+ depleted HSCT. By utilizing the IPDfromKM technique, we reconstructed time-to-event data from aggregated Kaplan-Meier curves, specifically focusing on overall survival (OS), disease-free survival (DFS), and GVHD-free, relapse-free survival (GRFS). Additionally, we conducted parallel meta-analyses to calculate the pooled incidences of GVHD, graft failure, mortality, as well as CMV and EBV reactivation, and sinusoidal obstruction syndrome (SOS) using aggregate data. All analyses were performed using STATA software. Our comprehensive literature search included publications up to May 2023, excluding studies with significant sample overlap. Results: The meta-analysis incorporated 817 children with AML/MDS or ALL from 12 studies. Successful primary engraftment was observed in 95% of patients (95% CI: 92 - 98), with an average time to neutrophil and platelet engraftment of 12 days. The incidence of acute GVHD grades I-II was 24% (95% CI: 14 - 34), while grades III and IV were 11% (95% CI: 3.0 - 0.18). Chronic GVHD was observed in 19% of patients (95% CI: 11 - 28). The relapse and graft failure rates were 25% (95% CI: 19 - 32) and 6% (95% CI: 2.0 - 9.0), respectively. The all-cause mortality was 34% (95% CI: 29 - 38), with HSCT-related mortality at 11% (95% CI: 8.0 - 13), while relapse-related mortality accounted for 22% (95% CI: 17 - 28). At a median follow-up of 2.55 years, the 1-year and 5-year OS rates were 74.7% (95% CI: 60.6 - 78.3) and 64.4% (95% CI: 59.9 - 68.5), respectively. No significant differences in OS were found between ALL and AML/MDS patients (HR= 0.99, 95% CI: 0.48 - 2.02, P=0.98) or between different donor types (Figure 1A). The DFS rates at 1- and 5-year were 72.8% (95%CI: 67.6 - 77.3) and 61.8% (95%CI: 56.1 - 67.0), respectively. No significant differences in DFS were observed between ALL and AML/MDS patients (HR = 0.74 95%CI: 0.48 - 1.14, P=0.17) or between different donor types (Figure 1B). The overall 1- and 5-year GRFS rates were 71.1% (95% CI: 64.1 - 77.4) and 63.0% (95% CI: 55.3 - 69.8), respectively. The overall incidence of CMV and EBV reactivation was 33% (95% CI: 19 - 46) and 16% (95% CI: 0 - 38), respectively. Conclusions: Our meta-analysis confirms the effectiveness and safety of TCRαβ and CD19-depleted HSCT for hematological malignancies, demonstrating high engraftment success, low graft failure, and a manageable incidence of acute and chronic GVHD. The consistently favorable outcome data across different donor types and malignancies support the broad applicability of this form of graft manipulation.

Impact of Facility Type on Survival in Chronic Myelomonocytic Leukemia: A Propensity Score Matched, National Cancer Database Analysis

Introduction Chronic myelomonocytic leukemia (CMML) is an MDS/MPN overlap syndrome with a heterogenous clinical presentation and limited therapeutic options. Given its rarity, we hypothesize that there may be disparate outcomes based on the type of treatment facility (academic versus community) similar to what has been observed in other myeloid malignancies such as acute myeloid leukemia (VR Bhatt AJH 2017). To that end, we performed an analysis of the National Cancer Database (NCDB) to assess the impact of academic status of the facility on overall survival (OS) in patients with CMML. Methods We identified patients in the NCDB by the ICD-O-3 code for CMML (9945); we excluded patients who did not receive treatment and those who received all or part of their treatment outside of the reporting facility. Importantly, baseline clinical characteristics, laboratory/mutational data, and treatment details are generally not available in the NCDB. Academic centers were defined as those with a peer-reviewed NCI-designated cancer center support grant or university medical school that provide postgraduate medical education in at least four program areas, as defined by the Commission on Cancer Accreditation program. The primary outcome was OS. Propensity score matching (PSM) was performed and after backwards selection, the following variables were used for matching: age, race, median income, urban/rural, education, Charlson comorbidity index (CCI). Cox proportional hazard multivariable regression was employed to identify independent predictors of survival in the PSM population. Results A total of 6290 patients were identified. Baseline characteristics based on facility type are shown in Table 1. Patients treated at an academic center were younger, with a higher prevalence of Black race and lower comorbidity burden. Academic centers also had a patient population with a significantly higher median household income, more private insurance, and higher education level as compared to non-academic centers. The median follow-up time was 14.6 months (95% CI 0.4-89.7). The median OS for the entire cohort was 59 months (95% CI 56.7-62.0) and the median survival was significantly longer in patients treated at an academic center (60.6 months [95% CI 57.5-64.8]) as compared to those treated at a non-academic center (57.3 months [95% CI 53.4-61.8]). In the PSM analysis, a cohort of 1884 patients treated at an academic center were matched to 1895 patients treated at a non-academic center. In an unadjusted analysis, there was no significant difference in median OS (p=0.3) between the academic and non-academic groups. However, in a multivariable analysis of the PSM populations that accounted for age, race, CCI, insurance, distance to center, and median income, patients treated at an academic center had a significantly improved survival as compared to those treated at a non-academic center (HR 0.82, 95% CI 0.71-0.94, p = 0.005, Figure 1). Discussion We found significant differences in the characteristics of CMML patients treated at academic versus non-academic centers. After PSM and multivariable adjustment, survival was significantly improved with treatment at an academic center versus non-academic. Although limited in the depth of information about CMML prognostic features and treatments, this relatively large analysis of CMML patients suggests that management of this rare disease at an academic center may be associated with improved survival outcomes. Future prospective studies to ascertain the underlying causes for survival discrepancy in CMML at academic versus non-academic centers may help identify patients that should be triaged to an academic facility.

Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations.

We discuss the clinical characteristics and prognostic significance of adult individuals with PTPN11 mutations who have developed acute myeloid leukemia (AML) (none acute promyelocytic leukemia). Next generation sequencing and Sanger sequencing were used to detect 51 gene mutations, and multiplex-PCR was used to detect 41 fusion genes from 232 de novo adult AML patients retrospectively. About 7.76% patients harbored PTPN11 mutations, 20 PTPN11 alterations were identified, all of which were missense mutations in the N-SH2 (n = 16) and PTP (n = 4) domains located in exon 3. Patients with PTPN11 mut had significantly higher platelet counts and hemoglobin levels (p < 0.001), which were mainly detected in M5 (n = 12, 66.67%, p < 0.001) subtype. Patients with MLL-AF6 positive showed a higher frequency of PTPN11 mut (p = 0.018) in the 118 AML cases. PTPN11 mut were accompanied by other mutations, which were NPM1 (44.44%), DNMT3A (38.89%), FLT3 (38.89%), and NRAS (17.2%). PTPN11 mut had a negative impact on the complete remission rate in M5 subtype patients (p < 0.001). However, no statistically significant effect on overall survival (OS) with PTPN11 mut patients in the whole cohort and age group (p > 0.05) was observed. Further analysis revealed no significant difference in OS among NPM1 mut/PTPN11 mut, NPM1 mut/PTPN11 wt, DNMT3A mut/PTPN11 mut, and DNMT3A mut/PTPN11 wt patients (p > 0.05). Multivariate analysis showed the proportion of bone marrow blasts ≥65.4% was a factor significantly affecting OS in PTPN11 mut patients (p = 0.043).

The Impact of Adjuvant Radiotherapy on Clinical Performance Status in Patients With Grade II Spinal Cord Astrocytoma - A Nationwide Analysis by the Neurospinal Society of Japan.

The impact of adjuvant radiotherapy on overall survival (OS) and progression-free survival (PFS) of patients with grade II spinal cord astrocytomas remains controversial. Additionally, the relationship between progression and clinical deterioration after radiotherapy has not been well investigated. This study included 53 patients with grade II intramedullary spinal cord astrocytomas treated by either subtotal, partial resection or open biopsy. Their clinical performance status was assessed immediately before operation and 1, 6, 12, 24, and 60 months after surgery by Karnofsky Performance Scale (KPS). Patients with and without adjuvant radiotherapy were compared. The groups with and without radiation comprised 23 and 30 patients with a mean age of 50.3 ± 22.6 years (range, 2-88 years). The mean overall disease progression rate was 47.1% during a mean follow-up period of 48.4 ± 39.8 months (range, 2.5-144.5 months). In the radiation group, 11 patients (47.8%) presented with progressive disease, whereas 14 patients (46.7%) presented with progressive disease in the group without radiation. There were no significant differences in OS or PFS among patients with or without adjuvant radiotherapy. KPS in both groups, especially radiation group, gradually decreased after operation and deteriorated before the confirmation of disease progression. Adjuvant radiotherapy did not show effectiveness regarding PFS or OS in patients with grade II spinal cord astrocytoma according to classical classification based on pathohistological findings.

Real-World Study of Overall Survival in Patients with Stage III Non-Small Cell Lung Cancer Treated with Chemoradiotherapy with or without Durvalumab and an Exploratory Analysis of Effective Radiation Dose to the Immune Cells

To investigate the real-world data on overall survival (OS) in patients with stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT) with or without consolidation durvalumab, and to perform an exploratory analysis on effective radiation dose to the immune cells (EDIC). In our multi-institutional retrospective study, patients who received CCRT between July 2018 and July 2019 for stage III NSCLC in Japan were investigated. EDIC was estimated using mean lung dose, mean heart dose, body volume, body mean dose, and body weight, as reported in the secondary analysis of RTOG 0617. The cut-off value of EDIC was calculated using the maximally selected log-rank statistics. One hundred and seventy-eight patients were eligible for the analysis (136 patients, CCRT with consolidation durvalumab [CCRT+D] cohort; 42 patients, CCRT cohort). The median follow-up period was 42.5 months. Three-year OS rates were 59.8% in the overall cohort: 60.5% in the CCRT+D cohort, and 58.0% in the CCRT cohort with no significant difference (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.45-1.27; P = 0.29). Univariate analysis showed that ECOG-PS, smoking history, histology, EGFR mutational status, gross tumor volume and EDIC were significantly associated with OS. Multivariate analysis showed that ECOG-PS 2, gross tumor volume ≥ 57 cm3 and EDIC ≥ 4.4 Gy were associated with poor OS. Among 21 EGFR-mutated patients, 3 year-OS rates were 64.7% in the CCRT+D cohort and 100% in the CCRT cohort, while 3 year-OS rates were 68.8% and 58.7% among 90 EGFR wild-type patients. Three-year OS rates were 64.6% and 47.6% for EDIC < 4.4 Gy and EDIC ≥ 4.4 Gy in the overall cohort (HR, 1.82; 95% CI, 1.14-2.90; P = 0.015). In the subgroup analysis, 66.3% vs. 44.4% in the CCRT+D cohort (HR, 2.01; 95% CI, 1.17-3.47; P = 0.016), and 59.0% vs. 56.1% in the CCRT cohort (HR, 1.20; 95% CI, 0.48-3.01; P = 0.70), respectively. Our real-world data in Japan showed that there was no significant difference in OS between the CCRT+D cohort and the CCRT cohort. High EDIC could be a risk for poor OS in patients treated with CCRT and consolidation durvalumab compared with those treated with CCRT.

Pretreatment eosinophil counts as a predictive biomarker in non-small cell lung cancer patients treated with immune checkpoint inhibitors.

The peripheral blood eosinophil count prior to treatment has potential as a predictive biomarker for a beneficial clinical response to cancer immunotherapies. Therefore, the present study investigated the impact of the eosinophil count on overall survival (OS) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICI). We retrospectively reviewed all patients diagnosed with NSCLC and treated with ICI monotherapy between March 2016 and August 2021 at National Hospital Organization Kochi Hospital and Tokushima University. A total of 166 patients were included. Fifty-five patients had an eosinophil count of less than 100 cells/μL (Eo < 100). Nighty-eight patients had an eosinophil count of 100 cells/μL or more, but less than 500 cells/μL (100 ≤ Eo < 500). Thirteen patients had an eosinophil count of 500 cells/μL or more (Eo ≥500). The median OS of all lung cancer patients was 476 days. The median OS of lung cancer patients with Eo <100, 100 ≤ Eo <500, and Eo ≥500 was 339, 667, and 143 days, respectively. A Kaplan-Meier univariate analysis showed a significant difference in OS between these three groups (p < 0.001). A Cox proportional regression analysis identified 100 ≤ Eo <500 (p = 0.04), ECOG PS score ≥ 2 (p = 0.02), tumor size ≥5 cm (p = 0.02), and PD-L1 ≥ 1% (p = 0.01) as independent predictors of OS. OS was significantly longer in ICI-treated NSCLC patients with a pretreatment eosinophil count of 100 ≤ Eo <500 than in the other patients and, thus, has potential as a new predictive biomarker.

Prognostic Performance of the China Liver Cancer Staging System in Hepatocellular Carcinoma Following Transarterial Chemoembolization.

To validate prognostic performance of the China liver cancer (CNLC) staging system as well as to compare these parameters with those of the Barcelona Clinic Liver Cancer (BCLC) staging system for Chinese hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE). This multicenter retrospective study included 1,124 patients with HCC between January 2012 and December 2020 from six Chinese hospitals. Based on overall survival (OS), the prognostic performance outcomes for the CNLC and BCLC staging systems were compared by model discrimination [C statistic and Akaike information criterion (AIC)], monotonicity of the gradient (linear trend chi-square test), homogeneity (likelihood ratio chi-square test), and calibration (calibration plots). A prospective cohort of 44 patients receiving TACE-based therapy included between January 2021 and December 2022 was used to prospectively validate the outcomes. Median OS was 19.1 (18.2-20.0) months, with significant differences in OS between stages defined by the CNLC and BCLC observed (p<0.001). The CNLC performed better than the BCLC regarding model discrimination (C-index: 0.661 vs. 0.644; AIC: 10,583.28 vs. 10,583.72), model monotonicity of the gradient (linear trend chi-square test: 66.107 vs. 57.418; p<0.001), model homogeneity (159.2 vs. 158.7; p<0.001). Both staging systems had good model calibration. Similar results were observed in the prospective cohort. Combining model discrimination, gradient monotonicity, homogeneity, and calibration, the CNLC performed better than the BCLC for Chinese HCC patients receiving TACE.

Local treatment Associated With Prognosis among Men With Metastatic Prostate Cancer: A SEER-Based Study.

In order to identify the impact of local treatment on overall survival (OS) and cancer-specific survival(CSS) in men with mPCa. Men with mPCa undergoing local treatment by radical prostatectomy (RP), radiotherapy (RT) including beam radiation and brachytherapy or no local treatment identified from Surveillance, Epidemiology, and End Results (SEER) database (2010-2015). To evaluate local therapy impact on OS and CSS in relation to baseline characteristics, univariate and multivariable Cox regression analysis was used to predict the prognostic value of local therapy in OS and CSS. A total of 902 (25.8%) patients received local treatment and 2598 (74.2%) patients did not receive local treatment in this study. The Kaplan-Meier curves showed that there was significant difference in OS between patients underwent local treatment and patients without local treatment (P=.013) but not in CSS (P=.068). While multivariate Cox regression analysis showed that local treatment may not significantly improve OS(P=.724). In subgroup analysis, Among patients with prostate-specific antigent (PSA)<10ng/ml, local treatment could significantly improve OS and CSS (all P < .05). Multivariate Cox regression analysis showed that local treatment could be used as an independent prognostic factor to improve OS in mPCa patients with PSA<10ng/ml (P=.031). Another multivariate Cox regression analysis demonstrated that patients with mPCa undergoing RP had better OS and CSS (all P < .05). Our results showed that local salvage therapy did not seem to be an independent prognostic factor in all mPCa patients, but we found that local therapy can show a better prognosis in patients with lower PSA levels. Compared with RT, patients who had experienced RP may have better prognosis. We still need prospective research to further study the application value of local treatment in mPCa patients.

Effects of [177Lu] Lu-PSMA-617 on overall survival in TheraP versus VISION randomized trials: An exploratory analysis.

5045 Background: Observed effects on overall survival (OS) differed in the first two randomized trials (RCTs) of [177Lu] Lu-PSMA-617 (LuPSMA) in metastatic, castration-resistant prostate cancer. TheraP randomized participants to LuPSMA or Cabazitaxel (CBZ). In TheraP, the CBZ group (n = 101) included 20 participants who crossed over to LuPSMA, and the LuPSMA group (n = 99) included 32 who crossed over to CBZ. VISION randomized participants to treatment with or without LuPSMA, plus physicians’ choice among protocol-defined treatments, excluding CBZ. Thirty-eight percent of control group participants in VISION had received CBZ prior to randomization. This study investigated explanations for differences in these RCTs in the observed effects of LuPSMA on OS. Methods: Individual participant data (IPD) on survival time from VISION was extracted from published survival curves for comparison with IPD from TheraP. Rank-preserving structural failure time (RPSFT) and inverse probability of censoring weighting (IPCW) were used in TheraP to estimate treatment effects on OS in counterfactual analyses assuming crossover had not occurred in either group, or in both groups. Results: OS was longer in the comparator group of TheraP than the comparator group of VISION (HR: 0.57, 95% CI 0.43 - 0.75) while OS was similar in the LuPSMA groups of VISION and TheraP (HR: 0.92, 95% CI 0.70 - 1.19). No significant differences in OS between the LuPSMA and CBZ groups of TheraP were apparent using counterfactual analyses assuming crossovers had not occurred (No crossover from CBZ: RPSFT HR 0.97, 95% CI 0.62 –1.52, IPCW HR 0.92, 95% CI 0.65-1.32; No crossover from LuPSMA: RPSFT HR 0.97, 95% CI 0.60–1.58, IPCW HR 0.82, 95% CI 0.55–1.24; No crossover from LuPSMA or CBZ: RPSFT HR 0.97, 95% CI 0.53-1.74, IPCW HR 0.82, 95% CI 0.53–1.27). Conclusions: The difference in observed effects of LuPSMA on overall survival in TheraP and VISION are better explained by the use of different comparator treatments in their control groups than by crossovers in TheraP from Cabazitaxel to LuPSMA, or LuPMSA to Cabazitaxel. Clinical trial information: NCT03392428 , NCT03511664 .

The impact of previous local therapy (LT) on overall survival (OS) in patients with advanced hepatocellular carcinoma (aHCC) treated with atezolizumab/bevacizumab (A+B) as first line systemic therapy.

e16129 Background: Treatment options for aHCC have drastically improved over the past few years with immunotherapy at the forefront. Ongoing studies aim to identify the benefit of immunotherapy in combination with local therapies, but there are no studies that analyze the impact of previous local therapy on OS in patients who later receive A+B for treatment of aHCC. This study aims to analyze the impact of previous local therapy on OS in patients with aHCC treated with first line A+B within the Veterans Health Administration (VHA). Methods: Patients with aHCC receiving first line systemic therapy with A+B at VHA between Dec 1, 2019 through Mar 1, 2022 were identified from the electronic medical record (EMR) using ICD-9 and ICD-10 codes. Abstractors reviewed the EMR and followed the patients from the date of diagnosis, date of local treatment and date of A+ B initiation until death or their last VHA visit with the study period ending on Jan 31, 2023. The Chi-Squared test was used to compare rates and the Mann-Whitney test was used to compare medians. Results: 332 patients with aHCC received A+B. 67% of patients received prior LT. Patients who received LT had better ECOG status, Child-Pugh classification, and BCLC staging at time of diagnosis. There was no difference in age at diagnosis, race/ethnicity, ALBI score at time of diagnosis or at time of starting A+B, or presence of extrahepatic spread at time of starting A+B. There was a statistically significant difference in time from HCC diagnosis to start of A+B, with patients who received LT having a longer interval time. There was a small but not statistically significant difference in median OS from the start of A+B, favoring people who received LT. Conclusions: Our unique retrospective study confirms that patients receiving LT have better OS from the time of diagnosis. Disease biology and LT response may be contributing to this survival benefit. However, the OS was similar from the time of initiation of A+B in patients receiving LT versus patients who did not receive any LT.[Table: see text]

MP33-11 P16 STATUS IS AN INDEPENDENT PREDICTOR OF OVERALL SURVIVAL IN METASTATIC PENILE CANCER IN A LARGE CONTEMPORARY COHORT

You have accessJournal of UrologyCME1 Apr 2023MP33-11 P16 STATUS IS AN INDEPENDENT PREDICTOR OF OVERALL SURVIVAL IN METASTATIC PENILE CANCER IN A LARGE CONTEMPORARY COHORT James Churchill, Ashwin Sachdeva, Craig Jones, Allaudin Issa, Christian Fankhauser, Andrew Hudson, Anna Tran, Pedro Oliveira, Helen Johnson, Maurice Lau, Arie Parnham, and Vijay Sangar James ChurchillJames Churchill More articles by this author , Ashwin SachdevaAshwin Sachdeva More articles by this author , Craig JonesCraig Jones More articles by this author , Allaudin IssaAllaudin Issa More articles by this author , Christian FankhauserChristian Fankhauser More articles by this author , Andrew HudsonAndrew Hudson More articles by this author , Anna TranAnna Tran More articles by this author , Pedro OliveiraPedro Oliveira More articles by this author , Helen JohnsonHelen Johnson More articles by this author , Maurice LauMaurice Lau More articles by this author , Arie ParnhamArie Parnham More articles by this author , and Vijay SangarVijay Sangar More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003266.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Penile squamous cell carcinoma (PSCC) is rare and there is a need to refine selection of patients for optimal management. Human papilloma virus infection is a known PSCC risk factor, measured by the histopathological presence of the p16 protein. This study has examined effect of p16 status on overall survival (OS) of PSCC patients managed at a tertiary referral centre. METHODS: We analysed retrospective data from a prospectively maintained database for patients with PSCC treated between 2003 and 2022. We excluded patients without reported p16 status. TNM stage was defined by histopathology (AJCC v8) except where fixed inguinal nodes (cN3), pelvic lymphadenopathy (cN3) or distant metastatic disease (M1) were present without histopathological confirmation. The primary outcome was OS (time from definitive primary surgery to death, censored for last follow-up). Multivariate Cox regression analysis for age, p16 status, TNM-stage and grade was performed. Audit approval was obtained. RESULTS: We identified 470 eligible patients. Median follow-up was 28 months (range 0-265). 118 patients (25%) did not undergo invasive lymph node staging (pNX). For the whole cohort, p16+ patients demonstrated 10% greater 5-year OS compared to p16- (71% versus 61%; Figure 1). After multivariate analysis (Table 1), there remained a significant difference in OS with 40% reduction in the risk of death for p16+ patients compared to p16-. On exploratory analysis by stage, only the N1 group retained this difference, suggesting that this is the group where p16 status may be of most clinical impact. CONCLUSIONS: Our data demonstrate that p16+ predicts for improved OS compared to p16- status in PSCC patients. After adjusting for age, stage and grade, this difference was retained in patients with N1 disease, suggesting that p16 status could be further explored as a predictive biomarker in this group. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e454 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information James Churchill More articles by this author Ashwin Sachdeva More articles by this author Craig Jones More articles by this author Allaudin Issa More articles by this author Christian Fankhauser More articles by this author Andrew Hudson More articles by this author Anna Tran More articles by this author Pedro Oliveira More articles by this author Helen Johnson More articles by this author Maurice Lau More articles by this author Arie Parnham More articles by this author Vijay Sangar More articles by this author Expand All Advertisement PDF downloadLoading ...

Abstract P4-06-05: Response to neoadjuvant chemotherapy among women with triple-negative breast cancer by HER2 expression status

Abstract Background: - Low levels of HER2 expression among women with HER2-negative breast cancer is an emerging target. In addition, prior studies have suggested that low levels of HER2 expression might confer resistance to chemotherapy among women with triple-negative breast cancer (TNBC). In this study, we assess the response to neoadjuvant chemotherapy among women with TNBC with varying degrees of HER2 expression. Methodology: - Utilizing the National Cancer Database, we identified adult women treated with neoadjuvant chemotherapy for a diagnosis of clinical TNM stage I to III triple-negative invasive ductal carcinoma of the breast between the years 2010 and 2018. Baseline characteristics were compared between HER2 immunohistochemistry (IHC) scores of 0, 1 +, and 2+ (Women with HER2 2+ expression had to be negative for amplification in the HER2 gene by FISH) using Chi-square for categorical variables. The odds of achieving a complete pathological response were compared among women with different HER2 expression statuses in a multivariate logistic regression model adjusting for age, race, ethnicity, grade of the tumor, and clinical TNM stage at diagnosis. A multivariate cox proportional hazards regression model was used to identify the prognostic effect of HER2 expression on overall survival (OS) adjusting for age at diagnosis, race, ethnicity, grade of tumor, and clinical TNM stage at diagnosis. Results: - A total of 11,038 women with HER2 IHC score of 0, 8,718 women with a score of 1+ and 2,700 women with a score of 2+ were included in the final analysis. The median age at diagnosis was 52 for women with a HER2 IHC score of 0, 53 for women with a HER2 IHC score of 1+ and 54 for women with an IHC score of 2+/FISH negative. The rates of complete pathological response among women with HER2 IHC scores of 0, 1+, and 2+ were 39.5%, 38.1%, and 36.1% respectively. In multivariate analysis, a significant difference in the odds of achieving complete pathological response was not observed for women with HER2 1+ (OR: 1.1, 95% CI: 0.95-1.20, p = 0.3) or HER2 2+ (OR: 0.9, 95% CI: 0.7-1.0, p = 0.1) tumors compared to women with HER2 IHC score of 0. In multivariate Cox regression analysis, women with TNBC with HER2 IHC score 2+ were found to have a better OS (Hazard Ratio [HR]: 0.88, 95% CI: 0.80-0.97, p = 0.01) compared to women with HER2 IHC score of 0 whereas a significant difference in OS was not observed between women with HER2 IHC scores of 0 and 1+ (HR: 0.95, 95% CI: 0.89–1.01, p = 0.1). Conclusion: - This study demonstrates that HER2 expression status does not influence the rates of complete pathological response to neoadjuvant chemotherapy in women with TNBC. However, women with HER2 IHC score of 2+ were found to have a favorable prognosis, which needs to be evaluated further in future studies. Citation Format: Pravash Budhathoki, Anish Shah, Suman Gaire, Utsav Joshi, Siddhartha Yadav. Response to neoadjuvant chemotherapy among women with triple-negative breast cancer by HER2 expression status [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-06-05.

Impact of number of treatment lines following first-line (1L) immuno-oncology (IO) combination on overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC).

673 Background: Across the world, treatment of patients with mRCC is heterogeneous with different access to treatment sequences and number of lines of therapy (LOTs) employed. For instance, patients receiving first line (1L) nivolumab+ipilimumab (NIVO+IPI) may be offered second-line (2L) and third line (3L) vascular endothelial growth factor receptor targeted kinase inhibitor (VEGFR-TKI), whereas patients receiving 1L pembrolizumab or avelumab in combination with axitinib (IO+AXI) may only receive one subsequent VEGFR-TKI in 2L. We aimed to examine whether these different treatment strategies impact overall survival (OS). Methods: Adult mRCC patients who received at least three LOTs starting with 1L NIVO+IPI or at least two LOTs starting with 1L IO+AXI from the International Metastatic RCC Database Consortium (IMDC) centers were included. Kaplan-Meier analyses were used to estimate median OS (time from 1L to death). Results were stratified by 1L IMDC prognostic risk. Results: Among 128 patients who received at least three LOTs starting with 1L NIVO+IPI (median age 61 years, 77% White, 77% male, 37% from the US), 14% had favorable, 61% had intermediate, and 26% had poor IMDC risk. The most common 2L treatments following 1L NIVO+IPI were sunitinib (38%), cabozantinib (27%), and pazopanib (20%). Among 104 patients who received at least two LOTs starting with 1L IO+AXI (median age 62 years, 75% White, 67% male, 38% from the US), 28% had favorable, 48% had intermediate, and 25% had poor IMDC risk. The most common 2L treatments following 1L IO+AXI were cabozantinib (57%) and sunitinib (10%). Median OS are presented in the table, which suggested no difference in survival for patients who received at least two LOTs starting with 1L IO+AXI compared to patients who received at least three LOTs starting with 1L NIVO+IPI. Conclusions: Treatment for patients with mRCC varies depending on the 1L regimen chosen and by country. Our results demonstrate that, even with potential guaranteed time bias and IMDC imbalances, there is no statistically significant difference in OS for patients who received at least three LOTs starting with 1L NIVO+IPI and patients who received at least two LOTs starting with 1L IO+AXI, suggesting that selecting effective treatments in 1L resulting in fewer LOTs may have similar clinical outcomes as multiple LOTs. [Table: see text]

The impact of resection margin distance on survival and recurrence in pancreatic ductal adenocarcinoma in a retrospective cohort analysis.

The prognostic effect of resection margin status following pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) remains controversial, even with the implementation of standardized pathological assessment. We therefore investigated the impact of resection margin (RM) status and RM distance in curative resected PDAC on overall survival (OS), disease-free survival (DFS) and recurrence. 108 patients were retrieved from a prospectively maintained database of a certified pancreatic cancer center. Distribution and relationships between circumferential resection margin (CRM) involvement (CRM≤1mm; CRM>1mm; CRM≥2mm) and their prognostic impact on OS and DFS were assessed using Kaplan-Meier statistics and the Log-Rank test. Multivariate logistic regression was used explain the development of a recurrence 12 months after surgery. 63 out of 108 patients had medial RM and 32 posterior RM involvement. There was no significant difference in OS and DFS between CRM≤1mm and CRM>1mm resections. Clearance at the medial margin of ≥2mm had an impact on OS and DFS, (RM≥2mm vs. RM<2mm: median OS 29.8 vs 16.8 months, median DFS 19.6 vs. 10.3 months). Multivariate analysis demonstrated that age, medial RM ≥2mm, lymph node status and chemotherapy were prognostic factors for OS and DFS. Posterior RM had no influence on OS or DFS. Not all RM seem to have the same impact on OS and DFS, and a clearance of 1mm for definition of a negative RM (i.e. CRM>1mm) seems not sufficient. Future studies should include more patients to stratify for potential confounders we could not account for. This study was registered with the German Clinical Trials Registry (reference number DRKS0017425).

The SOCS-1 -1478CA/del functional polymorphism (rs33989964) is associated with gastric cancer but is unrelated to overall survival.

In vitro studies have shown that the functional - 1478CA > del polymorphism (rs33989964) of the suppressor of cytokine signaling (SOCS)-1 gene is associated with an altered trascriptional activity. Here, we sought to examine the potential association of this polymorphism with the risk of gastric cancer (GC) and to analyze its prognostic impact on overall survival (OS). The study cohort consisted of 74 Turkish patients with GC and 52 healthy controls. Genotyping of the SOCS-1 -1478CA > del polymorphism was carried out using restriction fragment length polymorphism analysis. After allowance of age and sex, multivariable logistic regression analysis revealed that the carriage of the del allele of the SOCS-1 -1478CA > del polymorphism was independently associated with an increased risk of GC (odds ratio = 6.78, 95% confidence interval = 3.24-10.99, P < 0.001). Kaplan-Meier analysis revealed no significant differences in OS for patients harboring at least one del allele of rs33989964 compared with CA/CA homozygotes (log-rank test, P = 0.17). While the SOCS-1 -1478CA > del polymorphism is significantly associated with the risk of GC in the Turkish population, it does not affect OS.

Adjuvant Radiation and Survival Following Surgical Resection of Sinonasal Adenocarcinoma.

This study aims to investigate the utility of adjuvant radiation in patients who undergo surgical resection for the management of node-negative sinonasal adenocarcinoma (SNAC). Retrospective database review. The 2004-2016 National Cancer Data Base (NCDB) was used to extract patients with surgically resected node-negative SNAC. Kaplan-Meier survival analysis and Cox-Proportional Hazards Modelling were used to analyze the impact of adjuvant radiation on overall survival (OS) following surgery. 349 patients with SNAC underwent surgical resection. Of these patients, 154 (44.1%) received adjuvant radiotherapy (RT). Although there was no significant difference in race, age, or sex of those receiving RT, those receiving RT have more advanced diseases and are more likely to have positive margins. Kaplan Meier analysis showed no significant difference in 5-year OS in patient who received adjuvant RT in comparison to those who underwent surgical resection alone (65.7% vs. 72.6%, respectively; p=0.378). In addition, when looking at only patients with positive margins, 5-year OS still did not have a significant difference (73.8% vs. 61.6%, respectively; p=0.101). Only patients with clinical AJCC T4 showed a statistically significant survival benefit with adjuvant RT (56.9% vs. 29.9%, respectively; p=0.009). Adjuvant RT does not appear to provide a significant survival benefit in patients with resected SNAC, with the exception of those with clinically AJCC T4 disease. 4 Laryngoscope, 133:2603-2612, 2023.