Hazard Of Death For Patients Research Articles

Neurologic Recovery at Discharge and Long-Term Survival After Cardiac Arrest

Brain injury is the leading cause of death following cardiac arrest and is associated with severe neurologic disabilities among survivors, with profound implications for patients and their families, as well as broader societal impacts. How these disabilities affect long-term survival is largely unknown. To investigate whether complete neurologic recovery at hospital discharge after cardiac arrest is associated with better long-term survival compared with moderate or severe neurologic disabilities. This cohort study used data from 4 mandatory national registers with structured and predefined data collection and nationwide coverage during a 10-year period in Sweden. Participants included adults who survived in-hospital cardiac arrest (IHCA) or out-of-hospital cardiac arrest (OHCA) beyond 30 days and who underwent predefined neurologic assessment conducted by health care professionals at hospital discharge using the Cerebral Performance Category (CPC) scale between January 2010 and December 2019. Patients were divided into 3 categories: complete recovery (CPC 1), moderate disabilities (CPC 2), and severe disabilities (CPC 3-4). Statistical analyses were performed in December 2023. CPC score at hospital discharge. The primary outcome was long-term survival among patients with CPC 1 compared with those with CPC 2 or CPC 3 or 4. A total of 9390 cardiac arrest survivors (median [IQR] age, 69 .0 [58.0-77.0] years; 6544 [69.7%] male) were included. The distribution of functional neurologic outcomes at discharge was 7374 patients (78.5%) with CPC 1, 1358 patients (14.5%) with CPC 2, and 658 patients (7.0%) with CPC 3 or 4. Survival proportions at 5 years were 73.8% (95% CI, 72.5%-75.0%) for patients with CPC 1, compared with 64.7% (95% CI, 62.4%-67.0%) for patients with CPC 2 and 54.2% (95% CI, 50.6%-57.8%) for patients with CPC 3 or 4. Compared with patients with CPC 1, there was significantly higher hazard of death for patients with CPC 2 (adjusted hazard ratio [aHR], 1.57 [95% CI, 1.40-1.75]) or CPC 3 or 4 (aHR, 2.46 [95% CI, 2.13-2.85]). Similar associations were seen in the OHCA and IHCA groups. In this cohort study of patients with cardiac arrest who survived beyond 30 days, complete neurologic recovery, defined as CPC 1 at discharge, was associated with better long-term survival compared with neurologic disabilities at the same time point.

Treatment in certified cancer centers is related to better survival in patients with colon and rectal cancer: evidence from a large German cohort study

BackgroundCertified cancer centers aim to ensure high-quality care by establishing structural and procedural standards according to evidence-based guidelines. Despite the high clinical and health policy relevance, evidence from a nation-wide study for the effectiveness of care for colorectal cancer in certified centers vs. other hospitals in Germany is still missing.MethodsIn a retrospective cohort study covering the years 2009–2017, we analyzed patient data using demographic information, diagnoses, and treatments from a nationwide statutory health insurance enriched with information on certification. We investigated whether patients with incident colon or rectal cancer did benefit from primary therapy in a certified cancer center. We used relative survival analysis taking into account mortality data of the German population and adjustment for patient and hospital characteristics via Cox regression with shared frailty for patients in hospitals with and without certification.ResultsThe cohorts for colon and rectal cancer consisted of 109,518 and 51,417 patients, respectively, treated in a total of 1052 hospitals. 37.2% of patients with colon and 42.9% of patients with rectal cancer were treated in a certified center. Patient age, sex, comorbidities, secondary malignoma, and distant metastases were similar across groups (certified/non-certified) for both colon and rectal cancer. Relative survival analysis showed significantly better survival of patients treated in a certified center, with 68.3% (non-certified hospitals 65.8%) 5-year survival for treatment of colon cancer in certified (p < 0.001) and 65.0% (58.8%) 5-year survival in case of rectal cancer (p < 0.001), respectively. Cox regression with adjustment for relevant covariates yielded a lower hazard of death for patients treated in certified centers for both colon (HR = 0.92, 95% CI = 0.89–0.95) and rectal cancer (HR = 0.92, 95% CI = 0.88–0.95). The results remained robust in a series of sensitivity analyses.ConclusionsThis large cohort study yields new important evidence that patients with colorectal cancer have a better chance of survival if treated in a certified cancer center. Certification thus provides one powerful means to improve the quality of care for colorectal cancer. To decrease the burden of disease, more patients should thus receive cancer care in a certified center.

SURVIVAL ANALYSIS OF BREAST CANCER PATIENTS IN KANO STATE

Cancer is a deadly malignant disease and is prevalent in Sub Saharan Africa. Specifically, breast cancer is now the most popular cancer and the second leading cause of death in Nigeria among women. This research is aimed at assessing the length of life of patients and prognostic factors associated with survival of breast cancer patients. Research subjects were breast cancer patients who went to Aminu Kano Teaching hospital (AKTH), patient’s follow-up data were obtained from the medical records and pathological variables were obtained from the department of Pathology from 2018- 2022. The survival analysis was performed using Kaplan Meier, log rank and Cox proportional regression model(semi-parametric). The Kaplan Meier results reveals the overall survival to be 0.75(75%). The median survival time is approximately 44 months, that is the probability that half of the patients have died. From the log-rank test, the survival times significantly differ across groups of Tumor stages, Age groups, Lymph node stages and Treatment Types. Results for the Cox proportional hazards model shows that, Treatment type and Tumor stage breast cancer were the risk factor for death in breast cancer patients. It was found that the hazard of death is twice or more for patients with a tumor characterized as tumor stage IV compared to other tumor stages. The hazard of death for patients on Radiotherapy treatment was 1.4 times as patients on Chemotherapy or Hormonal-therapy treatment. The Proportional Hazard assumption was assessed and all the variables meets the assumption.

Association between posttreatment α-fetoprotein reduction and outcomes in real-world US patients with advanced hepatocellular carcinoma.

Clinical trials suggest α-fetoprotein (AFP) reduction may be prognostic among patients with advanced hepatocellular carcinoma. However, the association of AFP reduction with outcomes in real-world settings is unclear. Patients with advanced hepatocellular carcinoma between January 1, 2011, and June 30, 2021, first-line tyrosine kinase inhibitor, and baseline and posttreatment AFP values (closest to 8±2weeks after first-line initiation) were included. AFP reduction was defined as ≥20% decrease from baseline vs <20% or no decrease. Real-world overall survival and progression-free survival (rwPFS) were defined as time from posttreatment AFP measurement to death, and the first progression event or death, respectively. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazards models adjusted for potential confounders and baseline AFP. Effect modification by baseline AFP and hepatocellular carcinoma risk factors was assessed. Among 533 patients, median baseline AFP was higher in those with AFP reduction than those without (N=166, 210 µg/L vs N=367, 150 µg/L). There was a 35% decrease in hazard of death for patients with reduction vs without (aHR=0.65; 95% CI, 0.52-0.81; median, 10.3 vs 5.9months). Results were similar for rwPFS (aHR=0.66; 95% CI, 0.54-0.81; median, 4.6 vs 2.6months). AFP reduction was associated with better outcomes among patients with baseline AFP ≥400 µg/L or with history of hepatitis B virus, hepatitis C virus, or alcohol use. Only the interaction between baseline AFP and reduction in association with rwPFS was statistically significant. For certain etiologies, posttreatment AFP change may be more important than baseline AFP for prognosis. Further work should characterize the prognostic implications of longitudinal AFP changes during treatment. The prognostic value of the change in α-fetoprotein (AFP) concentration after treatment initiation is less established, particularly in real-world settings. Longitudinal data from a large nationwide cohort of patients with advanced hepatocellular carcinoma (HCC) treated with first-line tyrosine kinase inhibitor in routine practice revealed that ≥20% reduction in posttreatment AFP levels was associated with better real-world overall survival and progression-free survival after adjusting for baseline AFP levels and other factors. The results also suggested that the associations may be stronger among patients with a history of HCC risk factors (e.g., hepatitis C virus, alcohol) or with higher baseline AFP levels.

Post-Remission Outcomes in Patients with Acute Myeloid Leukemia (AML) Are Similar between Hypomethylating Agent/Venetoclax Therapy and Intensive Chemotherapy after Accounting for Measurable Residual Disease (MRD) Status

Background: Intensive chemotherapy regimens (IC; e.g., 7+3 or CPX-351) broadly target leukemic blast populations in acute myeloid leukemia (AML) by interfering with DNA replication, whereas hypomethylating agent/venetoclax therapy (HMA/ven) takes advantage of metabolic vulnerabilities in leukemic stem cells via inhibition of anti-apoptotic pathways. IC regimens are often targeted to 'fit', younger patients, while HMA/ven is typically used in patients who are older or who have significant comorbidities. Both therapeutic paradigms can induce morphologic remission, with resultant measurable residual disease (MRD) status remaining a prognostically significant factor. Here, we aim to determine whether post-remission outcomes in AML patients depend mainly on MRD status or are further modified by chosen induction (IC vs HMA/ven). Methods: Retrospective chart review was performed on adult (age 18 years and older) patients newly diagnosed with AML and treated at Johns Hopkins Hospital, Baltimore, MD between September 2014 and June 2021. Patients were excluded if they had promyelocytic or mixed phenotype leukemia. Complete remission (CR) was defined by <5% medullary blasts with no extramedullary disease and count recovery. Primary covariates of interest included age in years, performance status (PS; ECOG 0-1 for good vs 2-4 for poor), European LeukemiaNet (ELN) 2022 risk group, number of HMA/ven cycles to best response, hematopoietic stem cell transplantation (HCT) status, chemotherapy type (IC vs HMA/ven), and MRD status by multiparametric flow cytometry (MFC). Groups were compared using Wilcoxon rank sum, Kruskal-Wallis, and Fisher's exact tests. Laplace regression models were used to estimate subgroup median overall survivals (OS) in order to compare them using the Wald test. Associations between OS and the above covariates were examined in Cox models; one multivariable model included an interaction term for therapy type and MRD status. Analyses were performed using Stata version 17. Results: Of the 388 patients initially reviewed, 214 (55%) achieved a CR or CR with incomplete count recovery and were included in further analysis. Most (103 of 159) IC patients received 7+3; 20 received CPX-351 and 36 received a high-dose cytarabine-based regimen. Fifty-five patients received HMA/ven. The HMA/ven patients were significantly older than those receiving IC regardless of MRD status (median age 72 vs 58 years, respectively, P<0.001). MRD negative (MRD-) remission was achieved in 134 (84.3%) patients after IC and 44 (80.0%) patients after HMA/ven. Patients who achieved MRD- CRs after IC were more likely to undergo HCT than those with identical MRD status after HMA/ven (77.6% vs 40.9%, P<0.001) and were younger (median age 60 vs 73 years, P<0.001). Univariate analysis showed significantly decreased hazard of death in patients with favorable ELN 2022 risk score, MRD- status in first CR, and HCT (Table 1). Kaplan-Meier curves showed patients with MRD- remissions had superior survival to those with MRD positive (MRD+) remissions (median OS not reached vs. 21.9 months, P<0.05), whereas there was no statistically significant difference in median OS between therapies (36.1 months HMA/ven vs. 61.2 months IC). Patients in the IC, MRD- group and HMA/ven, MRD- group had similar outcomes (median OS not reached for both); both groups had superior survival to MRD+ groups (P<0.05; Figure 1). Multivariable analysis showed decreased hazards of death for ELN favorable risk patients (hazard ratio [HR] 0.49, 95% confidence interval [CI] 0.28-0.85) and those MRD- in first CR (HR 0.47, 95% CI 0.28-0.77) after adjusting for age, PS, therapy type, and cycles. In a subsequent model, an interaction term between therapy type and MRD status was not significant (HR=0.96, suggesting no difference in impact of MRD between therapy types). Conclusions: In this retrospective study evaluating outcomes in patients with AML, chemotherapy type does not appear to differentially impact survival by MRD status in those achieving remission. MRD status as measured by MFC significantly impacts survival when adjusting for relevant baseline covariates. These results suggest that obtaining deep, MRD- remissions matters regardless of whether these are achieved with HMA/venetoclax or intensive therapy. Ultimately, randomized controlled trials are needed to better determine the value of MRD in AML after different induction strategies. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Extraventricular site indicates higher grade but better prognosis in adult supratentorial ependymomas: a 14-year single-center retrospective cohort.

Supratentorial extraventricular ependymoma (STEE) and supratentorial intraventricular ependymoma (STIE) are two subsets of supratentorial ependymoma (SE). These two subsets have similar gene features and only differ in original sites: STEE occurs in the brain parenchyma, and STIE is located in ventricles and surrounded by cerebral spinal fluid. The present study aims to depict the diversities of these two subsets and elucidate the potential effects of the anatomic site on the tumor with the same type, grade, and molecular features. Sixty-six consecutive adult SE patients from 2008 to 2021 were enrolled in our study. Clinical data, pathological features, and long-term outcomes were analyzed retrospectively. Results demonstrated that adult STEE presented with a higher proportion of WHO grade 3 (P = .028) and higher Ki-67 index (≥10%) (P = .019) compared to adult STIE. Survival analysis demonstrated that patients of grade 3 STEE exhibited a significantly longer overall survival (OS) than patients of grade 3 STIE (median OS, 24.4 months vs. 13.0 months; P = .004). Grade 2 (hazard ratio (HR) = 0.217; P < .001) and gross total resection (GTR) (HR = 0.156; P < .001) were identified as favorable prognostic factors for all adult SE. The STEE was also associated with a lesser hazard of death for patients of grade 3 on multivariate analysis (HR = 0.263; P = .047). These findings suggested that the extraventricular site was an indicator for higher grade and better prognosis in adult supratentorial ependymoma.

MO416: Predicting Serum Bicarbonate in Non-Dialysis Dependent CKD Patients

Abstract BACKGROUND AND AIMS Metabolic acidosis (HCO3 &amp;lt; 22 mmol/L) is associated with an increased hazard of death in patients with chronic kidney disease (CKD) [1, 2]. It is further associated with muscle wasting, bone disease, hypoalbuminemia, increased inflammation, protein malnutrition, and progression of CKD [3]. Hospital Civil de Guadalajara is an urban public hospital serving a population of low socioeconomic status for whom HCO3 measurements are not included in their healthcare services and create costs around 70% of which our population cannot afford. We aimed to develop a model allowing us to predict HCO3 in CKD patients and tested its diagnostic performance. METHOD Patients at CKD stage 3–5 from our pre-dialysis clinic were included in this retrospective, cross-sectional study which served as a model development. Creatinine, weight, height, calcium, phosphorus, sodium, potassium, chloride, urea, presence of diabetes, total body water calculated by the Watson equation and eGFR calculated with the CKD-EPI formula were utilized. We performed uni- and multivariate linear regression between measured serum HCO3 and the available variables. A hypothesis-driven step-wise approach for parameter inclusion based on the Akaike Information criterion and optimization of the coefficient of determination was employed to construct the final model predicting serum HCO3. Diagnostic performance for detecting metabolic acidosis using the estimated HCO3 (eHCO3) was evaluated by receiver operating characteristics curve (ROC) analysis and computation of sensitivity, specificity and the positive and negative predictive values (PPV, NPV). Post-test probabilities at different pre-test probabilities (prevalence) were assessed using Bayes’ theorem. RESULTS We screened 1089 patients and included 284 patients [62 (21 IQR), 56% male, 69±14kg, 27% at CKD stage 3 and 34% and 40% at stage 4 and 5, respectively] in the analysis. The final model [eHCO] = 21.47 + 0.61 Ca + 0.43 Na + 0.95 TBW-0.61 Pi-0.51 K-0.53 Cl-0.008 Urea + 0.95 If diabetic had an adjusted R2:0.57, RMSE 2.4 on 275df, P-value: &amp;lt;0.001. The mean difference between HCO3 and eHCO was 0 (95% CI −4.9 to 4.9). Diagnostic performance quantified as AUC ROC 0.87 (95% CI 0.83–0.91). At a prevalence of metabolic acidosis of 56% with a chosen threshold of 20 mEq/L, the model has a sensitivity of 56% and specificity of 95% and a PPV of 94% and NPV of 63%, at a prevalence of 56%. Simulation of the post-test probabilities using Bayesian analysis is shown in Figure 1. CONCLUSION At a considerably high specificity of 95%, we can make predictions with a relatively low risk of treating subjects without metabolic acidosis with bicarbonate. Given the cost saving for the patients and the added insights and diagnostic capability, we believe that the prediction of serum HCO3 by biochemical parameters as done in our model will prove useful in settings with limited resources such as our uninsured urban population in Mexico. Validation of our model is the next step and planned future research.

Clinicogenomic characterization of prostate cancer liver metastases.

The site of prostate cancer metastasis is an important predictor of oncologic outcomes, however, the clinicogenomic characteristics associated with the site are not well-defined. Herein, we characterize the genomic alterations associated with the metastatic site of prostate cancer. We analyzed clinical and genomic data from prostate cancer patients with metastatic disease and known metastatic sites from publicly available targeted sequencing data. Prostate cancer metastasis to the liver versus other sites of metastasis conferred a high hazard for death in patients with metastatic prostate cancer (HR: 3.96, 95% CI: 2.4-6.5, p < 0.0001). Genomic analysis of metastatic tissues of prostate cancer-specific genes demonstrated that liver metastases were more enriched with MYC amplification (29.5% vs. 9.8%, FDR = 0.001), PTEN deletion (42% vs. 20.8%, FDR = 0.005), and PIK3CB amplification (8.2% vs. 0.9, FDR = 0.005) compared to other sites. No point mutations were significantly associated with liver metastasis compared to other metastatic sites. Liver metastases in prostate cancer are associated with poor survival and aggressive genomic features, including MYC-amplification, PTEN-deletion, and PIK3CB-amplification. These findings could have prognostic, treatment, and trial implications.

The value of innovation: association between improvements in survival of advanced and metastatic non-small cell lung cancer and targeted and immunotherapy

BackgroundSignificant improvements in mortality among patients with non-small cell lung cancer (NSCLC) in the USA over the past two decades have been reported based on Surveillance, Epidemiology, and End Results (SEER) data. The timing of these improvements led to suggestions that they result from the introduction of new treatments; however, few studies have directly investigated this. The aim of this study was to investigate the extent to which population level improvements in survival of advanced and/or metastatic NSCLC (admNSCLC) patients were associated with changes in treatment patterns.MethodsWe utilized a de-identified database to select three cohorts of patients with admNSCLC: (1) patients with non-oncogene (EGFR/ALK/ROS1/BRAF) positive tumors, (2) patients with ALK-positive (ALK+) tumors, and (3) patients with EGFR-positive (EGFR+) tumors. All patients were diagnosed with admNSCLC between 2012 and 2019. Multivariable Cox models adjusting for baseline characteristics and receipt of targeted and immunotherapy were utilized to explore the relationship between these variables and changes in the hazard of death by calendar year in each cohort.ResultsWe included 28,154 admNSCLC patients with non-oncogene positive tumors, 598 with ALK+ tumors, and 2464 with EGFR+ tumors eligible for analysis. After adjustment for differences in baseline characteristics, the hazard of death in patients who had non-oncogene positive tumors diagnosed in 2015, 2016, 2017, 2018 ,and 2019 was observed to be 12%, 11%, 17%, 20%, and 21% lower respectively than that for those diagnosed in 2012. Upon additionally adjusting for receipt of first line or second line immunotherapy, the decrease in the hazard of death by calendar year was no longer observed, suggesting improvements in survival observed over time may be explained by the introduction of these treatments. Similarly, decreases in the hazard of death were only observed in patients with ALK+ tumors diagnosed between 2017 and 2019 relative to 2012 but were no longer observed following adjustment for the use of 1st and later generation ALK inhibitors. Among patients with EGFR+ tumors, the hazard of death did not improve significantly over time.ConclusionOur findings expand on the SEER data and provide additional evidence suggesting improvements in survival of patients with advanced and metastatic NSCLC over the past decade could be explained by the change in treatment patterns over this period.

Neoadjuvant chemotherapy with interval debulking surgery versus chemotherapy alone for advanced epithelial ovarian cancer

<h3>Objectives:</h3> The treatment of advanced epithelial ovarian cancer (EOC) involves a combination of cytoreductive surgery and chemotherapy. For patients with unresectable disease or extensive comorbidities at the time of diagnosis, administration of neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) has been shown to be a non-inferior treatment approach compared with primary cytoreduction, and has gained wider acceptance in the past decade[i],[ii]. Additionally, GOG 213 showed that in patients with platinum-sensitive, recurrent ovarian cancer, secondary surgical cytoreduction followed by chemotherapy did not result in longer overall survival than chemotherapy alone[iii], The approach of chemotherapy without IDS has not been reassessed since the advent of VEG-F and PARP inhibitors and checkpoint blockade. This study aims to examine the survival outcomes of patients treated with chemotherapy alone versus those who underwent IDS. <h3>Methods:</h3> A retrospective cohort study was conducted at a single institution after IRB approval. Patients with Stage III or IV EOC diagnosed between 2005 and 2019 who received NACT due to unresectable disease or medical comorbidities were included. Patient demographics and clinical characteristics were collected. The primary outcome was the hazard of death in patients who underwent IDS (treated as a time-dependent covariate), compared to those who received chemotherapy alone. Age was categorized into groups: < 50 years, 50-64 years, and 65+ years. Kaplan-Meier curves stratified by IDS status were estimated using a landmark analysis conditional upon surviving at least 6 months post-diagnosis. <h3>Results:</h3> 81 patients met inclusion criteria, 50 (62%) received NACT + IDS, and 31 (38%) received chemotherapy alone. Four (5%) patients had <i>BRCA</i> mutations. Of the 50 patients who underwent IDS, 41 (82%) patients had an optimal debulking and 40 (80%) received additional adjuvant chemotherapy. The major surgical complication rate was 14% and the rate of upper abdominal surgery was 22%. The rate of chemotherapy toxicity was 29% in the chemotherapy alone group and 34% in the IDS group. The univariate estimate for the hazard of death in women who underwent IDS was 0.85, with a 95% CI: (.32, 2.3), p-value=.75. Adjusting for age, parity and BMI, the hazard ratio was estimated to be 1.03 with a 95% CI: (.35, 3.0), p-value=.96. There was no statistically significant difference in survival when comparing IDS status in patients who survived at least 6 months from diagnosis (p=0.45). <h3>Conclusions:</h3> While the observed hazard of death was lower in the patients who underwent IDS versus those who did not, the results were not statistically significant. While this study is underpowered to validate chemotherapy only as a treatment regimen for patients with EOC, the results warrant further large-scale investigation to assess the utility of treating advanced EOC with chemotherapy alone, particularly among the <i>BRCA</i> mutated/HRD population with chemosensitive tumors.

The role of adjuvant chemotherapy in FIGO stage IB grade 3 endometrial endometrioid adenocarcinoma treated with surgery and postoperative radiotherapy

Objectives: The optimal treatment of FIGO stage IB grade 3 endometrial endometrioid adenocarcinoma remains unknown. It is unclear if adjuvant chemotherapy (CHT) in addition to adjuvant radiotherapy enhances survival in this subgroup of endometrial cancer patients. The goals of the present study were to perform a National Cancer Database (NCDB) analysis in this cohort of patients to 1) compare overall survival following treatment with a hysterectomy and adjuvant radiotherapy with or without CHT, 2) evaluate CHT utilization in the United States, and 3) investigate which factors are associated with survival in stage IB grade 3 endometrioid adenocarcinoma patients. Methods: Patients diagnosed between 2004 and 2015 with FIGO stage IB grade 3 endometrial endometrioid adenocarcinoma treated with hysterectomy and postoperative radiotherapy with or without adjuvant systemic CHT were identified in the NCDB. Overall survival (OS) was assessed with Kaplan-Meier curves, and differences between groups were compared with the log-rank test. A Cox model was constructed to evaluate survival after controlling for confounders, and logistic regression was used to reveal predictors of CHT use. Results: While the receipt of CHT was associated with a trend toward increased 5-year OS from 68.1% to 74.7% (p=0.059), this association did not reach statistical significance on propensity score weighted (p=0.073) and multivariate analyses (adjusted HR (aHR) 0.86; CI: 0.70-1.06; p=0.15) as shown in the figure. Moreover, there was some evidence of a differential CHT effect in patients who did not undergo a lymphadenectomy (LND; p=0.056); CHT was associated with a trend toward reduced hazard of death in patients with LND (aHR=0.82, CI: 0.66-1.01, p=0.0634) but not in patients who did not undergo LND (aHR=1.70, CI: 0.86-3.35, p=0.1255). Patients who underwent brachytherapy as opposed to external beam radiotherapy, had lymphovascular space invasion (LVSI), were 59 years or younger, were diagnosed in the more recent years of the study and treated in higher facility case volume centers were more likely to: receive adjuvant chemotherapy. No LND (HR 1.51; CI: 1.13-2.03; p=0.0057), positive LVSI (HR 1.71; CI: 1.36-2.16; p 70 (HR 2.61; CI: 2.03-3.36; p Download : Download high-res image (275KB) Download : Download full-size image Conclusions: Adjuvant CHT plus radiotherapy was associated with a non-statistically significant increase in OS in FIGO stage IB grade 3 endometrioid adenocarcinoma patients compared to those treated with adjuvant radiotherapy alone. This potential effect is most apparent in patients who underwent LND.

Racial/ethnic, socioeconomic, and geographic survival disparities in adolescents and young adults with primary central nervous system tumors.

Disparities in survival by race/ethnicity, socioeconomic status (SES), and geography in adolescent and young adult (AYA) patients with central nervous system (CNS) tumors have not been well studied. A retrospective cohort study utilizing the Surveillance, Epidemiology, and End Results (SEER) database was conducted for AYA patients diagnosed with primary CNS tumors. Adjusted hazard ratios (aHR) were calculated using a multivariate Cox proportional hazard model to evaluate the association between race/ethnicity, SES, rurality, and hazard of death. All minority groups showed an increased hazard of death with greatest disparities in the high-grade glioma cohort. Lower SES was associated with an increased hazard of death in non-Hispanic White (NHW) patients (aHR 1.12; 95% confidence interval [CI] 1.01-1.24), non-Hispanic Black (NHB) patients (aHR 1.34; 95% CI 1.00-1.80), and patients aged 25-29 years (aHR 1.29; 95% CI 1.07-1.55). Mediation analysis showed an indirect effect of SES on the effect of race/ethnicity on the hazard of death only among NHB patients, with SES accounting for 33.7% of the association between NHB and hazard of death. Rurality was associated with an increased hazard of death for patients in the lowest SES tertile (aHR 1.31; 95% CI 1.08-1.59) and NHW patients (aHR 1.20; 95% CI 1.08-1.34). Patients identified as a racial/ethnic minority, patients with a lower SES, and patients residing in rural areas had an increased hazard of death. Further studies are needed to understand and address the biological, psychosocial, societal, and economic factors that impact AYA neuro-oncology patients at highest risk of experiencing poorer outcomes.

P09.13 Bone Metastases and Overall Survival in Patients with Metastatic Non-Small Cell Lung Cancer Treated with Pembrolizumab

Bone metastases (BM) and skeletal-related events (SRE) are a common cause of morbidity in patients with metastatic non-small cell lung cancer (mNSCLC). Data on the impact of BM on overall survival (OS) in patients treated with immune checkpoint inhibitors (ICI) is limited. Here we report the incidence, impact on survival, and risk factors for SRE in patients with mNSCLC treated with first-line pembrolizumab monotherapy or pembrolizumab plus chemotherapy. We conducted a retrospective study of patients with mNSCLC treated with first-line pembrolizumab or pembrolizumab plus chemotherapy at our institution from 2017-2020. The associations between SRE and categorical variables were studied using Fisher’s exact test and with continuous variables using the Kruskal-Wallis test. Kaplan-Meier plots were used to visualize survival curves. The association between baseline BM and OS was examined using a Cox proportional hazard model. OS was calculated from date of ICI initiation to death from any cause or last follow-up. We identified a cohort of 202 patients: 93 (46%) treated with pembrolizumab and 109 (54%) treated with pembrolizumab plus chemotherapy; 39 (19%) had squamous histology and 163 (81%) had nonsquamous histology; median age 62.7; median OS 33.7 months (95% CI: 17.2 – NR). In our cohort, 87 (43%) patients had BM at time of ICI initiation and 47 (23%) developed SRE after ICI initiation. Patients who developed SRE were more likely to have baseline BM than those without SRE (91.5% vs 28.4%, p<0.001). Development of BM during treatment with ICI and performance status were also significantly associated with SRE (p<0.001 and p=0.006, respectively). Patients with BM at time of ICI, or development of new or progression of existing BM while on ICI, had shorter survival than those without (Figure 1a and Figure 1b, respectively). In multivariate survival analysis, the hazard of death for patients with baseline BM was 2.85 times those without (HR=2.85, 95% CI: 1.53, 5.29, p-value=0.0009) after controlling for age, BMI, performance status, histology, PD-L1 expression, smoking, and SRE. The use of bone-modifying agents (BMA) was not associated with OS, osseous progression, or risk of SRE. The presence of BM at time of ICI was associated with shorter survival after controlling for multiple clinical characteristics. These patients represent a high-risk cohort for worse outcomes when treated with ICI alone or in combination with chemotherapy. In our cohort BMA were not associated with increased OS or decreased risk of osseous progression or SRE.

Donor and Recipient Individual Factors As Predictive Markers of Overall Survival After Allogeneic Hematopoietic Stem Cell Transplantation; Dream or Reality

Low overall survival (OS) still is a major concern of allogeneic hematopoietic stem cell transplantation (allo-HSCT), which is affected by many individual and environmental factors. In this study, we retrospectively evaluated the association of donor and recipient individual factors with the overall survival of 206 patients who underwent allo-HSCT. Donor and recipient prognostic factors consisted of donor and recipient age, donor-recipient gender status, recipient body mass index (BMI), underlying disease, recipient cytomegalovirus (CMV) serostatus, and time from diagnosis to transplant (DTT) were included in the overall survival analysis. In univariable analysis, recipient age, donor-recipient gender status, underlying disease, recipient CMV serostatus, and DTT were significantly associated with the OS. The hazard of death in patients with DTT less than 14 months was 38% lower than those with a DTT higher than 14 months (P=0.06). Multivariate analysis showed that patients with aplastic anemia (HR=3.58; P=0.11) and Hodgkin’s disease (HR=3.89; P=0.11) have a much lower survival than unclassified diseases. Moreover, patients with acute myeloid leukemia and acute lymphoblastic leukemia showed better outcomes compared to the unclassified group. The donor and patient characteristics such as age, CMV serostatus, underlying disease, and time from diagnosis to transplantation could influence the overall survival of patients after allo-HSCT.

Association between imaging response and survival following neoadjuvant chemotherapy in patients with resectable colorectal liver metastases: A cohort study.

The association between the imaging response (structural or metabolic) to neoadjuvant chemotherapy (neoCT) before colorectal liver metastasis (CRLM) and survival is unclear. A total of 201 patients underwent their first CRLM resection. A total of 94 (47%) patients were treated with neoCT. A multivariable, Cox proportional hazard regression analysis was performed to compare overall survival (OS) and progression-free survival (PFS) between response groups. Multivariable regression analysis of the CT/MRI (n = 94) group showed no difference in survival (OS and PFS) in patients who had stable disease/partial response (SD/PR) or complete response (CR) versus patients who had progressive disease (PD) (OS: HR, 0.36 (95% CI: 0.11-1.19) p = .094, HR, 0.78 (95% CI: 0.13-4.50) p = .780, respectively), (PFS: HR, 0.70 (95% CI: 0.36-1.35) p = .284, HR, 0.51 (0.18-1.45) p = .203, respectively). In the FDG-PET group (n = 60) there was no difference in the hazard of death for patients with SD/PR or CR versus patients with PD for OS or PFS except for the PFS in the small CR subgroup (OS: HR, 0.75 (95% CI: 0.11-4.88) p = .759, HR, 1.21 (95% CI: 0.15-9.43) p = .857), (PFS: HR, 0.34% (95% CI: 0.09-1.22), p = .097, HR, 0.17 (95% CI: 0.04-0.62) p = .008, respectively). There was no convincing evidence of association between imaging response to neoCT and survival following CRLM resection.

Joint Modelling of the Relationship between CD4 Cell Count and Survival Analysis of HIV Infected Patients Receiving Antiretroviral Therapy, Gweru, Zimbabwe

Introduction: The main objective of this research is to apply joint modelling technique to assess the relationship between cd4 cell count and survival of ART patients in Gweru, Zimbabwe. The Cox proportional hazards model is mainly used in modelling survival data when the true values of the time-varying covariates are observed. However, most of these measurements are observed with error and to circumvent this problem, measurements are taken longitudinally to reduce the bias caused using such observed measurements in the Cox proportional hazards models. Methods: We conducted secondary data analysis on the Gweru district ART cohort data for the period 2006 to 2010. The association between CD4 cell count and survival time of the patient was determined using a joint longitudinal-survival model. The factors that affected cd4 cell changes were determined using mixed linear regression model and factors associated with survival of ART patients was determined using a Cox proportional hazard model. Shared parameters were used to determine the association between cd4 cell count and survival of the ART patient. Results: A statistically significant direct effect of gender on survival was observed -0.003 (95% CI: -001, -0.002). Also, a highly negative significant association was observed -9.48 (95% CI: -11.7, -7.23), indicating that female patients with high levels of lncd4 had reduced hazard of death compared to male patients. Place of residents of the ART patient had a significant direct effect on survival -0.66 (95% CI: -0.01, 0.003). There is also a highly negative significant association -10.0 (95% CI: -12.4, -7.67), indicating that patients in urban areas and with high lncd4 cell counts had a reduced hazard of death compared to patients in rural areas. Age had a direct effect on survival as the hazard of death increases as we move from one age group to another. A highly negative significant association was observed -9.4 (95% CI: -11.6, -7.17) indicating that the hazard of death for patients with high lncd4 decreases as we move down the age groups.

Infiltrating Tumor Border Configuration is a Poor Prognostic Factor in Stage II and III Colon Adenocarcinoma

Tumor border configuration (TBC) is a prognostic factor in colorectal adenocarcinoma; however, the significance of TBC is not well-documented in colon adenocarcinoma alone. Our aim was to study the effect of TBC on overall and disease-free survival in stage II and III colon adenocarcinoma. We included patients with stage II and III colon adenocarcinoma who were surgically treated at a tertiary medical center between 2004 and 2015, to ensure long-term follow-up. Patients were stratified into four groups based on stage and TBC. A Cox regression was used to model the relationship of groups while accounting for relevant confounders. The cohort consisted of 700 patients (371 stage II and 329 stage III). Infiltrating TBC was statistically significantly associated with stage (p < 0.001) and extramural vascular invasion (p < 0.001), but not histologic grade (p = 0.7). Compared with pushing TBC, infiltrating TBC increased the hazard of death by a factor of 1.8 [95% confidence interval (CI) 1.4-2.4; p < 0.001] and 1.7 (95% CI 1.3-2.2; p < 0.001). The hazard of death in patients with stage II disease (infiltrating TBC) or stage III disease (pushing TBC) was not significantly different (adjusted hazard ratio 1.1, 95% CI 0.7-1.7; p = 0.8). Infiltrating TBC is a high-risk feature in patients with stage II and III colon adenocarcinoma. Stage II disease patients with infiltrating TBC and who are node-negative should be considered for adjuvant chemotherapy.

Germline and somatic DNA damage repair gene mutations potentially predict the efficacy of relevant treatment in Chinese patients with pancreatic ductal adenocarcinoma.

e16732 Background: PDAC is a fatal disease with molecular heterogeneity, inducing differences in biological behaviour and therapeutic strategy. We conducted a study to reveal the mutation landscape of Chinese PDAC patients, and investigate the predictive role of germline and somatic DNA damage repair (DDR) status in precise treatment. Methods: 195 PDAC patients were enrolled from multiple medical centers of China between Jan 2016 to Nov 2019. Baseline clinical or genetic characteristics, and survival status were collected. NGS were performed on paraffin-embedded resected tissues or peripheral blood using a panel of 417 genes, including 50 DDR-related genes. Survival analysis was conducted using Kaplan-Meier, and Cox proportional hazard regression model. Results: The main driver genes were KRAS, TP53, CDKN2A, and SMAD4. Patients with KRAS mutation showed worse OS than those without (p = 0.048). DDR deficiency were identified in 15.38% of overall patients, mainly occurred in BRCA2 (4.62%), ATM (4.10%), RAD50 (1.54%) and MLH1 genes (1.03%). No significant improvement of OS existed between patients with or without DDR mutations (p = 0.88). Treatment with olaparib (adjusted HR, 0.2550; P = 0.0720) or platinum-based chemotherapy (adjusted HR, 0.1308; P = 0.0185) respectively decreased hazard of death in patients with DDR mutation. Besides BRCA gene, ATM mutant patients treated with olaparib harbored prolonged median OS than those without olaparib treatment (22.25 vs 15.2 month). Despite a little higher PD-L1 expression rate were seen in DDR mutant patients (29.17% vs 20.51%), no statistical correlation between tumor mutation burden level and DDR mutation was identified. And in patients treated with PD-1 blockade, 2 patients of DDR wild-type group both had SD, whereas of the remaining 5 patients with DDR deficiency, 1 was evaluated as PR, 3 as SD, and 1 as PD (ORR, 0 wt vs 20% mut). Conclusions: In this multi-center retrospective study, we deciphered the intra-tumoral genetic heterogeneity in Chinese PDAC population, which differs from western patients cohort to some extent. We found the potential role of germline and somatic DDR mutation status in predicting the response to olaparib and platinum-based chemotherapy, especially with BRCA or ATM mutation. However, DDR alteration was limited in prediction of hypermutational status and sensitivity to PD-1 blockade. Our study may provide a valuable evidence for clinical application of DDR mutation as a potential biomarker for precise treatment.

Immune status and the efficacy of radiotherapy on overall survival for patients with localized Merkel cell carcinoma: An analysis of the National Cancer Database.

Immunosuppressed (IS) patients with Merkel cell carcinoma (MCC) have worse outcomes compared to immunocompetent (IC) patients, and it is unclear if adjuvant radiotherapy (RT) is beneficial for these patients. We sought to determine the effect of immune status on adjuvant RT efficacy regarding overall survival (OS) for patients with localized MCC. This was an observational study of National Cancer Database (NCDB) identifying patients with stage I/II or III MCC with known immune status diagnosed from 2010 to 2014. The median follow-up time was 29months. OS was described using Kaplan-Meier methods and compared for subgroups by immune status and adjuvant RT using log-rank tests, multivariable Cox regression and interaction effect testing. A total of 2049 IC and 255 IS patients were included. Adjuvant RT was associated with decreased hazard of death for stage I/II MCC (HR 0.65, CI 0.54-0.78) adjusting for factors including immune status. Interaction effect testing did not demonstrate a significant difference in the effect of adjuvant RT on OS between IC and IS status in either stage I/II or III MCC (both P values>0.05). In this observational study, adjuvant RT was associated with decreased hazard of death for patients with stage I/II MCC regardless of immune status. Adjuvant RT should be considered for both IS and IC patients with localized MCC.

Immune status and the efficacy of adjuvant radiotherapy for patients with localized Merkel cell carcinoma of the head and neck.

Immunosuppressed (IS) patients are at increased risk for developing Merkel cell carcinoma (MCC) with worsened outcomes compared to immunocompetent (IC) patients. We sought to determine the effects of immune status on the efficacy of adjuvant RT regarding OS for patients with stage I, II or III (localized) MCC of the head and neck. The National Cancer Database was queried for patients with resected, localized MCC of the head and neck with known immune status. Kaplan-Meier methods were used to describe OS. Log-rank tests, multivariable Cox regression models and interaction effect testing were used to compare OS by subgroup categorized by patient and treatment factors including immune status and adjuvant RT receipt. A total of 892 (89.6%) IC and 104 (10.4%) IS patients with MCC of the head and neck were included. Adjuvant RT was associated with improved 3-year OS rate for both IS patients (49.4% vs. 35.5%, p = 0.0467) and stage I/II IC patients (72.4% vs. 62.9%, p = 0.0092). Adjuvant RT was associated with decreased hazard of death (HR 0.77, 95% CI 0.62-0.95). Interaction effect testing did not demonstrate a difference in the efficacy of adjuvant RT on OS between IC and IS status (p = 0.157). In this NCDB analysis, adjuvant RT was associated with decreased hazard of death for patients with localized MCC of the head and neck regardless of immune status and should be considered for both IS and IC patients.