Difference In Hazard Of Death Research Articles

Utility of bioselection with neoadjuvant chemotherapy for organ preservation in patients with T4 laryngeal cancer

BackgroundNeoadjuvant chemotherapy for induction selection of definitive treatment (IS) protocols have shown excellent outcomes for organ preservation and survival in patients with T3 laryngeal squamous cell carcinoma (LSCC). We seek to evaluate survival and organ preservation outcomes in T4 LSCC patients treated with IS protocols. MethodsRetrospective cohort of advanced T3 and T4 LSCC patients who underwent IS protocols based upon potential for preserving a functional larynx. Patients received one neoadjuvant cycle of platinum-based chemotherapy with either 5-fluorouracil or docetaxel or with two cycles of platinum-based chemotherapy with docetaxel and a Bcl-2 inhibitor. Patients who achieved ≥ 50 % response as determined by radiographic review and/or endoscopic evaluation received definitive chemoradiation. Patients who had < 50 % response after IS underwent total laryngectomy (TL) followed by post-operative radiation +/- chemotherapy. ResultsAmongst T4 patients, 114 met inclusion criteria including 89 who underwent IS protocols and 25 who received an upfront TL. In total, 76.0 % of T3 patients and 71.9 % of T4 patients responded to IS and underwent definitive chemoradiation. There was no significant difference in hazard of death between T4 IS and T4 TL patients (HR: 0.9, p = 0.86). Among responders, there was no significant difference in 5-year laryngectomy-free survival (T3 – 59.6 %, T4 44.3 %, p = 0.15) or laryngeal preservation by T stage (T3 – 72.8 %, T4 – 73.0 %, p = 0.84). ConclusionsSelect T4 patients may benefit from organ preservation using IS protocols with similar response rates to patients with T3 tumors, without compromising survival when compared to upfront TL.

Real-world comparison of low- versus high-dose continuous 5FU infusion in patients receiving triplet chemotherapy plus bevacizumab for newly diagnosed metastatic colorectal cancer (mCRC).

62 Background: Several randomized trials demonstrated an overall survival (OS) benefit to triplet chemotherapy (5-FU, oxaliplatin, and irinotecan) plus bevacizumab compared to doublet chemotherapy plus bevacizumab in patients with newly diagnosed mCRC, though with higher rates of neutropenic fever and diarrhea. These trials used high-dose continuous infusion 5-FU (3,200 mg/m2/48 hours), but national guidelines suggest low-dose continuous infusion 5-FU (2,400mg/m2/48 hours) due to lower tolerance in U.S. patients. We performed a retrospective cohort study in a U.S. population to compare the effectiveness of low- vs high-dose continuous infusion 5FU in patients undergoing triplet chemotherapy plus bevacizumab for newly diagnosed mCRC. Methods: We used the nationwide Flatiron Health electronic health record-derived database, comprising de-identified patient-level structured and unstructured data curated via technology-enabled abstraction from ~280 cancer clinics. Patients with newly diagnosed mCRC who initiated triplet chemotherapy plus bevacizumab between 10/23/14 and 10/31/22 with non-missing height, weight, and dosing data were included. 5FU infusion doses of 2,000 – 2,799 mg/m2 were categorized as low-dose while those &gt;/= 2,800 mg/m2 were categorized as high-dose. OS from first-line treatment initiation was assessed by dosing group using the Kaplan Meier method with log-rank testing. Multivariable analysis with adjustment for pre-specified variables with imbalance (defined by standardized difference &lt; - 0.10 or &gt; 0.10) was performed using multivariable Cox proportional hazards modeling. Missing data were imputed using multiple imputation with chained equations. Results: Among 320 patients included, 244 received low-dose and 76 patients received high-dose continuous infusion 5FU. Imbalance between low- and high-dose groups was observed in the use of 5FU bolus (23% vs 3%), year of metastatic diagnosis 2018 - 2022 (80% vs 55%), mean irinotecan dose (156.4 vs 160.5 mg/m2), left-sided primary (73% vs 64%), MMR deficiency (3% vs 6%) and mean CEA (478 vs 691 µg/L). In univariate analysis, median OS was 33 months (95% CI 26 – 39) in the low-dose group compared to 34 months (95% CI 24 – 48) in the high-dose group (HR 1.16; 95% CI 0.79 – 1.69; p = 0.44). After adjusting for imbalanced covariates, there was no difference in hazard of death between low- and high-dose groups (HR 0.99; 95% CI 0.64 – 1.53; p = 0.97). Conclusions: In this real-world, U.S. population with newly diagnosed mCRC receiving triplet chemotherapy plus bevacizumab, there was no association with survival between low- vs high-dose continuous infusion 5FU. This supports current guidelines recommending low-dose continuous infusion 5FU (2,400mg/m2/48 hours) for patients with mCRC receiving triplet chemotherapy in the U.S.

Real-world comparison of triplet- versus doublet-chemotherapy with bevacizumab in patients with newly diagnosed metastatic colorectal cancer (mCRC).

3574 Background: Meta-analysis of five randomized intensification trials in mCRC demonstrated an overall survival (OS) benefit of triplet chemotherapy (5FU/leucovorin, oxaliplatin, irinotecan) plus bevacizumab (Triplet/Bev) compared to doublet chemotherapy plus bevacizumab (Doublet/Bev) (HR 0.81). Guidelines recommend first-line Triplet/Bev for patients with excellent performance status and normal organ function who can withstand increased toxicity, but such patients are less represented in the real world. In this retrospective cohort study, we examine the real-world effectiveness of Triplet/Bev compared to Doublet/Bev in the U.S. Methods: We used the nationwide Flatiron Health electronic health record-derived database, comprising de-identified patient-level structured and unstructured data curated via technology-enabled abstraction from ~ 280 cancer clinics. Included were mCRC patients treated with first-line Triplet/Bev or Doublet/Bev between 10/23/14 and 10/31/22. OS by treatment was assessed using the Kaplan Meier method and adjustment for confounding variables was performed using Cox proportional hazards modeling with stabilized inverse probability of treatment weighting (IPTW). Pre-specified confounding variables included age, gender, race/ethnicity, year of metastatic diagnosis, health insurance, practice setting, KRAS/NRAS/BRAF mutation status, MMR/MSI status, synchronous/metachronous metastases, primary tumor sidedness, CEA, renal dysfunction, hepatic dysfunction, and ECOG performance status. Missing data were imputed using multiple imputation with chained equations. Results: Among 10,016 patients, 391 (3.9%) received Triplet/Bev and 9,625 (96.1%) received Doublet/Bev. Patients who received Triplet/Bev were younger (median age 52 vs 63 years) and were more likely to be treated at academic practices (27% vs 8%), to have synchronous metastatic disease (83% vs 65%), and to have KRAS/NRAS/BRAF wild-type disease (30% vs 17%). In the univariate analysis, median OS was 30.0 months (95% CI 24.7 – 34.7) in the Triplet/Bev cohort versus 23.4 months (95% CI 22.8 – 24.1) in the Doublet/Bev cohort (HR 0.73; 95% CI 0.62 – 0.85; p &lt; 0.001). In Cox proportional hazards modeling with IPTW, there was no significant difference in hazard of death between Triplet/Bev and Doublet/Bev (HR 0.92; 95% CI 0.75 – 1.12; p = 0.4). Conclusions: In this large, national, real-world population of patients with mCRC, first-line treatment with Triplet/Bev was not associated with improved survival compared to Doublet/Bev after accounting for differences in baseline patient characteristics. The benefit to Triplet/Bev observed in randomized trials does not translate well to a more heterogeneous, real-world population. Sub-group analyses including by age, tumor sidedness, KRAS/NRAS/BRAF status, and baseline CEA level will be performed.

Impact of poverty and neighborhood opportunity on outcomes for children treated with CD19-directed CAR T-cell therapy

AbstractChildren living in poverty experience excessive relapse and death from newly diagnosed acute lymphoblastic leukemia (ALL). The influence of household poverty and neighborhood social determinants on outcomes from chimeric antigen receptor (CAR) T-cell therapy for relapsed/refractory (r/r) leukemia is poorly described. We identified patients with r/r CD19+ ALL/lymphoblastic lymphoma treated on CD19-directed CAR T-cell clinical trials or with commercial tisagenlecleucel from 2012 to 2020. Socioeconomic status (SES) was proxied at the household level, with poverty exposure defined as Medicaid-only insurance. Low-neighborhood opportunity was defined by the Childhood Opportunity Index. Among 206 patients aged 1 to 29, 35.9% were exposed to household poverty, and 24.9% had low-neighborhood opportunity. Patients unexposed to household poverty or low-opportunity neighborhoods were more likely to receive CAR T-cell therapy with a high disease burden (>25%), a disease characteristic associated with inferior outcomes, as compared with less advantaged patients (38% vs 30%; 37% vs 26%). Complete remission (CR) rate was 93%, with no significant differences by household poverty (P = .334) or neighborhood opportunity (P = .504). In multivariate analysis, patients from low-opportunity neighborhoods experienced an increased hazard of relapse as compared with others (P = .006; adjusted hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.3-4.1). There was no difference in hazard of death (P = .545; adjusted HR, 1.2; 95% CI, 0.6-2.4). Among children who successfully receive CAR T-cell therapy, CR and overall survival are equitable regardless of proxied SES and neighborhood opportunity. Children from more advantaged households and neighborhoods receive CAR T-cell therapy with a higher disease burden. Investigation of multicenter outcomes and access disparities outside of clinical trial settings is warranted.

Sex Differences in Intensity of Care and Outcomes After Acute Ischemic Stroke Across the Age Continuum.

Sex differences in stroke care and outcomes have been previously reported, but it is not known whether these associations vary across the age continuum. We evaluated whether the magnitude of female-male differences in care and outcomes varied with age. In a population-based cohort study, we identified patients hospitalized with ischemic stroke between 2012 and 2019 and followed through 2020 in Ontario, Canada, using administrative data. We evaluated sex differences in receiving intensive care unit services, mechanical ventilation, gastrostomy tube insertion, comprehensive stroke center care, stroke unit care, thrombolysis, and endovascular thrombectomy using logistic regression and reported odds ratios (ORs) and 95% CIs. We used Cox proportional hazard models and reported the hazard ratios (HRs) and 95% CI of death within 90 or 365 days. Models were adjusted for covariates and included an interaction between age and sex. We used restricted cubic splines to model the relationship between age and care and outcomes. Where the p-value for interaction was statistically significant (p < 0.05), we reported age-specific OR or HR. Among 67,442 patients with ischemic stroke, 45.9% were female and the median age was 74 years (64-83). Care was similar between both sexes, except female patients had higher odds of receiving endovascular thrombectomy (OR 1.35, 95% CI [1.19-1.54] comparing female with male), and these associations were not modified by age. There was no overall sex difference in hazard of death (HR 95% CI 0.99 [0.95-1.04] for death within 90 days; 0.99 [0.96-1.03] for death within 365 days), but these associations were modified by age with the hazard of death being higher in female than male patients between the ages of 50-70 years (most extreme difference around age 57, HR 95% CI 1.25 [1.10-1.40] at 90 days, p-interaction 0.002; 1.15 [1.10-1.20] at 365 days, p-interaction 0.002). The hazard of death after stroke was higher in female than male patients aged 50-70 years. Examining overall sex differences in outcomes without accounting for the effect modification by age may miss important findings in specific age groups.

Effect of Adjuvant Chemotherapy After SBRT for Node Negative, Non-Metastatic Non-Small Cell Lung Cancer

Administration of adjuvant chemotherapy (ACT) after surgical resection of a tumor ≥4cm is standard of care based on studies demonstrating improved overall survival. No such standard exists for tumors ≥ 4cm treated with stereotactic body radiation therapy (SBRT), and thus, administration of ACT remains variable across institutions. Using the National Cancer Database (NCDB), we aim to analyze overall survival (OS) in patients who undergo SBRT followed by ACT for localized non-small cell lung cancer (NSCLC). Additionally, we seek to identify predictors for receipt of ACT.Patients with node negative, non-metastatic NSCLC treated with definitive SBRT between 2004-2017 were identified from the NCDB. Patients were grouped into tumor size < 4cm or ≥4cm, and by use of ACT within 30 days of SBRT. Demographics were described by treatment. Logistic regression was used to assess the association between tumor size and treatment, adjusting for age, gender, race and comorbidities. Overall survival was calculated from date of end of radiation to date of death or last follow up. Multivariable Cox proportional regression was used to investigate the association between tumor size, treatment type, and OS, adjusting for the factors above.Of the 17441 patients identified meeting the inclusion criteria, 195 received ACT after SBRT (1.1%). Forty-nine percent of these patients were male, and 91% were white. The median age of patients who received ACT was 69. Twenty-six percent of the patients who received ACT had tumors ≥ 4cm (n = 51). There was a significant difference in hazard of death; patients with tumors ≥ 4cm without ACT (n = 1310) had worse OS as compared to those with tumors < 4cm without ACT (n = 15936) (HR 1.45; 95% CI 1.34-1.56, P < 0.0001). This difference became non-significant when comparing ≥4cm with ACT versus < 4cm without ACT (HR 1.17; P = 0.40). On pairwise comparison, there was no difference in hazard of death when comparing tumors ≥ 4cm with ACT versus ≥4cm without ACT (HR 0.81; P = 0.26). On multivariate analysis, tumor size ≥ 4cm was a significant predictor for receipt of ACT (OR 5.08; 95% CI 3.64-7.07, P < 0.0001). Older patients (OR 0.93 per 10yr increase; 95% CI 0.92-0.95, P < 0.0001) and those with comorbidities (OR 0.73 any vs no comorbidities; 95% CI 0.54-0.97, P = 0.032) were less likely to receive ACT. Notably, there was no difference between sex and race, white versus non-white, in administration of ACT.Patients with tumors ≥4cm treated with SBRT without ACT have decreased OS as compared to those with tumors < 4cm who are similarly treated without ACT. This survival decrement disappears when comparing tumors ≥4cm with ACT to tumors < 4cm without ACT suggesting a benefit to ACT. While there was no difference in OS between patients with tumors ≥4cm with or without ACT, this could be due to the small number of patients with tumors ≥4cm who received ACT. These findings identify a need to further study the roll of systemic therapy after SBRT.

Abstract 14418: Association Between 2018 Unos Heart Transplant Policy Changes and Likelihood of Transplant for Patients in Rural versus Urban Settings

Introduction: United Network for Organ Sharing (UNOS) recently extended the radius for which a heart transplant candidate can be matched with a donor in order to improve transplantation access for the most critically-ill patients. However, this means that smaller transplant centers serving rural populations may not retain the hearts that were donated within their geographic area. It is unknown whether the UNOS policy change of 2018 was associated with differences in likelihood of heart transplantation or death on the waiting list for patients from rural versus urban (metropolitan or micropolitan) settings. Methods: Using the Scientific Registry of Transplant Recipients, we analyzed U.S. adult patients who were listed for heart transplant from January 2017 through January 2020. Patients were stratified by home zipcodes to either metropolitan, micropolitan, or rural settings. Fine and Gray proportional hazard regression models were used to estimate the sub-distribution hazard ratio (SHR) of heart transplantation with death or removal from transplant list as a competing event according to geographic residence with date of UNOS policy change October 18 2018 as a time-varying covariate. Interaction (p-int) tests were performed between geographic setting and time of policy change. Results: Among 8756 patients, 82% were from metropolitan, 9% micropolitan, and 9% rural settings. The 2018 UNOS policy change was associated with increased receipt of heart transplantation within each geographic setting [metropolitan SHR 1.41 (95%CI: 1.33-1.50); micropolitan SHR 1.30 (95%CI: 1.08-1.56); rural SHR 1.33 (95%CI: 1.10-1.62); p-int=0.60]. Policy changes were not significantly associated with death on the transplant list for any geographic setting [metropolitan SHR 0.97 (95%CI: 0.82-1.14); micropolitan SHR 1.25 (95%CI: 0.80-1.96); rural SHR 0.89 (95%CI: 0.55-1.46); p-int=0.52]. Conclusions: Independent of geographic location, the 2018 UNOS policy change for heart transplantation was associated with increased heart transplantation and no significant difference in hazard of death. Additional follow-up is needed to determine whether improvements are sustained.

Long-term survival in patients who had CABG with or without prior coronary artery stenting

ObjectiveTo conduct a large-scale, single-centre retrospective cohort study to understand the impact of prior percutaneous coronary intervention (PCI) on long-term survival of patients who then undergo coronary artery bypass graft...

193. Comparison of Survival for MSSA and MRSA Endocarditis

BackgroundPrior studies have yielded conflicting findings regarding outcomes for MRSA vs. MSSA infective endocarditis (IE). Our experience suggests that MSSA IE is not any less severe than MRSA IE. The purpose of this study was to compare survival in MSSA and MRSA IE.MethodsEpisodes of IE caused by Staphylococcus aureus were identified from the Cleveland Clinic Infective Endocarditis Registry. Only the first episode was included for each patient. Acceptance for surgery was considered surgical treatment. Survival from the surgical decision date was compared for MSSA vs. MRSA endocarditis using multivariable Cox proportional hazards regression. Selection of variables for the model was done by stepwise backward elimination from a collection of clinically important baseline variables.ResultsBetween January 1, 2008 and January 1, 2010, 76 episodes of IE caused by S. aureus were identified. The mean (SD) patient age was 58 (15) years, 46 (61%) were males, 14 (18%) had a prior history of IE, 33 (43%) had diabetes mellitus, 22 (29%) had end-stage renal disease (ESRD), 27 (36%) had prosthetic valve endocarditis (PVE), 70 (92%) had left side involvement, 27 (36%) had invasive disease, 59 (78%) were referred patients, and 39 (51%) were treated surgically. The mean (SD) time to decision on surgery was 6 (7) days. Of these episodes 40 (53%) had MSSA IE and 36 (47%) had MRSA IE. There was no difference in hazard of death between MSSA and MRSA IE (HR 0.98, 95% C.I. 0.54–1.78, P-value 0.96), after adjusting for age, ESRD, prior history of IE, PVE, invasive disease, calendar year, and surgical treatment, which were the significant explanatory variables in the multivariable analysis. Survivals predicted by the model for a reference patient with MSSA IE and MRSA IE are shown in the figure.ConclusionPreliminary findings suggest that survival in MSSA IE may be similar to that in MRSA IE. The study is limited by its small sample size. The study finding will need confirmation with a larger sample. Disclosures All authors: No reported disclosures.

ATCT-29INVESTIGATING THE EFFECT OF REIRRADIATION OR SYSTEMIC THERAPY IN PATIENTS WITH GBM AFTER TUMOR PROGRESSION: A SECONDARY ANALYSIS OF THE NRG ONCOLOGY/RTOG 0525

BACKGROUND: There is limited evidence regarding which salvage treatment approach may be of most benefit for glioblastoma patients who progress following standard chemo-radiation treatment. METHODS: This secondary analysis of RTOG 0525 investigated the effect of reirradiation or systemic treatment in patients with tumor progression. Survival time was calculated from date of progression. Survival from first progression was estimated and compared between patients receiving neither radiation or systemic therapy, systemic therapy alone, or any radiation treatment. Patient characteristics were compared between groups and the Cox proportional hazards model was used to compare hazard of death controlling for potential confounders. RESULTS: A total of 637 patients who progressed with recorded information on their non-protocol therapy, excluding those who died less than half a month after progression, were analyzed. 267 patients (42%) received neither radiation or systemic treatment at progression. 88 patients (14%) received some form of radiation treatment. 282 patients (44%) received systemic treatment only. Patients who received no treatment had a median survival (MS) of 4.8 months, lower than radiation treatment (11.3 months), or systemic therapy (10.6 months). However, there was no survival difference between patients who received systemic therapy and those who received radiotherapy (p = 0.3808). Cox models, controlling for potential confounders, demonstrate no difference in hazard of death (1.13, 95% CI 0.8-1.5) between treatment arms. Patients receiving neither therapy had a statistically significant increased hazard of death (2.45, 95% CI: 1.9-3.1). CONCLUSIONS: Salvage treatments after GBM tumor progression were highly variable. Patients who received radiation with or without systemic therapy had a similar MS as those receiving systemic therapy only. Either treatment was statistically significantly better than no treatment. However, this may be the result of poorer functional status of untreated patients. SUPPORT: This project was supported by grants U10CA21661, U10CA180868, U10CA180822 and U10CA37422 from the NCI and Merck.

Effect of surgical treatment on mortality after acetabular fracture in the elderly: a multicenter study of 454 patients.

Controversy exists regarding the effect of operative treatment on mortality after acetabular fracture in elderly patients. Our hypothesis was that operative treatment would confer a mortality benefit compared with nonoperative treatment even after adjusting for comorbidities associated with death. Retrospective study. Three University Level I Trauma Centers. All patients aged 60 years and older with acetabular fractures treated from 2002 to 2009 were included in the study. Four hundred fifty-four patients were identified with an average age of 74 years. Sixty-seven percent of the study group was male and 33% female. One of 4 treatments: nonoperative management with early mobilization, percutaneous reduction and fixation, open reduction and internal fixation, acute total hip arthroplasty. Kaplan-Meier survival curves were created, and Cox proportional hazards models were used to calculate unadjusted and adjusted hazard ratios (HRs) for covariates of interest. In contrast to previous smaller studies, the overall mortality was relatively low at 16% at 1 year [95% confidence interval (CI), 13-19]. Unadjusted survivorship curves suggested higher 1-year mortality rates for nonoperatively treated patients (21% vs. 13%, P < 0.001); however, nonoperative treatment was associated with other risk factors for higher mortality. By accounting for these patient risk factors, our final multivariate model of survival demonstrated no significant difference in hazard of death for nonoperative treatment (0.92, P = 0.6) nor for any of the 3 operative treatment subgroups (P range, 0.4-0.8). As expected, we did find a significantly increased hazard for factors such as the Charlson comorbidity index [HR, 1.25 per point (95% CI, 1.16-1.34)] and age [HR, 1.08 per year of age more than 70 years (95% CI, 1.05-1.11)]. In addition, associated fracture patterns (compared with elementary patterns) significantly increased the hazard of death with a ratio of 1.51 (95% CI, 1.10-2.06). The operative treatment of acetabular fractures does not increase or decrease mortality, once comorbidities are taken into account. The reasons for this are unknown. Regardless of the causes, the decision for operative versus nonoperative treatment of geriatric acetabular fractures should not be justified based on the concern for increased or decreased mortality alone. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Does Type of Tumor Histology Impact Survival among Patients with Stage IIIB/IV Non-Small Cell Lung Cancer Treated with First-Line Doublet Chemotherapy?

Chemotherapy regimens may have differential efficacy by histology in nonsmall cell lung cancer (NSCLC). We examined the impact of histology on survival of patients (N = 2,644) with stage IIIB/IV NSCLC who received first-line cisplatin/carboplatin plus gemcitabine (C/C+G) and cisplatin/carboplatin plus a taxane (C/C+T) identified retrospectively in the SEER cancer registry (1997–2002). Patients with squamous and nonsquamous cell carcinoma survived 8.5 months and 8.1 months, respectively (P = .018). No statistically significant difference was observed in survival between C/C+G and C/C+T in both histologies. Adjusting for clinical and demographic characteristics, the effect of treatment regimen on survival did not differ by histology (P for interaction = .257). There was no statistically significant difference in hazard of death by histology in both groups. These results contrast the predictive role of histology and improved survival outcomes observed for cisplatin-pemetrexed regimens in advanced nonsquamous NSCLC.