Robust Predictor Of Survival Research Articles

Deep PSA response and extended time‐to‐nadir as robust predictors of survival in Asian patients with de novo metastatic hormone‐sensitive prostate cancer receiving upfront intensified treatment

AbstractIntroductionIn de novo metastatic hormone‐sensitive prostate cancer (mHSPC) treated with upfront intensification using androgen receptor signaling inhibitor or chemotherapy (Docetaxel), achieving a PSA nadir less than 0.2 ng/mL, indicative of superior survival in trials, may often be unattainable in real‐world settings. We explored the predictive value of the degree of PSA decline and time to PSA nadir (TTPN) on oncological outcomes.MethodsA prospectively maintained database of consecutive prostate cancer cases in Hong Kong was accessed. Patients diagnosed with de novo mHSPC from 2016 to 2022 and treated with upfront intensification were included in this analysis. Landmark analysis on PSA kinetics at 6‐months following treatment intensification was performed. They were classified based on 1) TTPN (≥6 months vs. <6 months), and 2) a combined response (deep responders achieving both ≥95% PSA decline and TTPN ≥ 6 months vs. shallow responders). Multivariable regression analysis was employed to identify the effects of confounders.FindingsA total of 131 patients were included in this analysis. Classifying patients by combined response best predicted survival outcomes. Deep responders had better progression‐free survival (HR = 0.56; 95%CI = 0.34–0.91; p = 0.019), overall survival (HR = 0.50; 95%CI = 0.26–0.97; p = 0.036), and cancer‐specific survival (HR = 0.43; 95%CI = 0.19–0.99; p = 0.042). Difference in overall survival remained significant after adjustment in multivariable regression analysis.ConclusionOur analysis demonstrates that alternative PSA targets can predict treatment response and survival outcomes in de novo mHSPC patients in a real‐world setting, providing valuable information for patient counselling and potentially guiding future trial design.

TCF3 as a multidimensional biomarker: oncogenicity, genomic alterations, and immune landscape in pan-cancer analysis.

Transcription factor 3 (TCF3), a pivotal member of the TCF/LEF family, plays a critical role in tumorigenesis. Nonetheless, its impact on the tumor microenvironment (TME) and cancer phenotypes remains elusive. We perform an exhaustive analysis of TCF3 expression, DNA variation profiles, prognostic implications, and associations with the TME and immunological aspects. This study is based on a large-scale pan-cancer cohort, encompassing over 17,000 cancer patients from multiple independent datasets, validated by in vitro assays. Our results show that TCF3/4/7 exhibits differential expression patterns between normal and tumor tissues across pan-cancer analyses. Mutational analysis of TCF3 across diverse cancer types reveals the highest alteration rates in biliary tract cancer. Additionally, mutations and single nucleotide variants in TCF3/4/7 are found to exert varied effects on patient prognosis. Importantly, TCF3 emerges as a robust predictor of survival across all cancer cohorts and among patients receiving immune checkpoint inhibitors. Elevated TCF3 expression is correlated with more aggressive cancer subtypes, as validated by immunohistochemistry and diverse cohort data. Furthermore, TCF3 expression is positively correlated with intratumoral heterogeneity and angiogenesis. In vitro investigations demonstrate that TCF3 is involved in epithelial-mesenchymal transition, migration, invasion, and angiogenesis. These effects are likely mediated through the interaction of TCF3 with the NF-κB/MMP2 pathway, which is modulated by IL-17A in human uveal melanoma MUM2B cells. This study elucidates, for the first time, the significant associations of TCF3 with DNA variation profiles, prognostic outcomes, and the TME in multiple cancer contexts. TCF3 holds promise as a molecular marker for diagnosis and as a potential target for novel therapeutic strategies, particularly in uveal melanoma.

Dynamics and survival associations of T cell receptor clusters in patients with pleural mesothelioma treated with immunotherapy

BackgroundImmune checkpoint inhibitors (ICIs) are now a first-line treatment option for patients with pleural mesothelioma with the recent approval of ipilimumab and nivolumab. Mesothelioma has a low tumor mutation burden...

Patient-reported geriatric assessment-based frailty index among older adults with gastrointestinal malignancies.

Older adults with cancer are at increased risk of treatment-related toxicities and excess mortality. We evaluated whether a patient-reported geriatric assessment (GA) based frailty index can identify those at risk of adverse outcomes. Older adults (≥60 years) enrolled in a single-institutional prospective registry underwent patient-reported GA at initial evaluation in our medical oncology clinic. Using deficit accumulation method, we constructed a 44-item frailty index (CARE-FI), categorizing patients as robust, pre-frail, and frail. The primary outcome was overall survival (OS). Secondary outcomes included (a) functional decline at 3 months post-therapy (b) incident grade ≥3 treatment-related toxicities at six-month post-treatment. We used multivariate Cox and logistic regression models respectively to study the impact of frailty on primary and secondary outcomes. We identified 589 older adults with a median age of 69 years; 55% males and 73% Whites. Overall, 168 (29%) were pre-frail and 230 (39%) frail. Being frail (vs. robust) was associated with worse OS (Hazards Ratio, HR 1.83, 95% Confidence Interval, CI 1.34-2.49, p < 0.001) after adjusting for age, sex, race/ethnicity, cancer type, cancer stage, and line of therapy. Similarly, frailty was associated with increased risk of functional decline (OR 3.01; 95% CI 1.33-6.81; p =0.008) and grade ≥3 non-hematologic toxicities (OR 3.65; 95% CI 1.54-8.69; p=0.003) but not hematologic toxicities (OR 1.01; 95% CI 0.46-2.22; p=0.97). Our frailty index using a patient-reported GA is a robust predictor of survival, functional decline, and treatment related toxicity among older adults with GI malignancies.

Log odds of positive lymph nodes is a robust predictor of survival and benefits from postoperative radiotherapy in stage IIIA-N2 resected non-small cell lung cancer.

BackgroundThe significance of postoperative adjuvant radiotherapy (PORT) on the survival of resected IIIA‐N2 non–small cell lung cancer (NSCLC) remains controversial. Here, we aimed to determine the predictive value of the three nodal classifications which might aid in PORT decision‐making.MethodsA total of 4797 patients with stage IIIA‐N2 resected NSCLC were identified in the Surveillance, Epidemiology and End Results (SEER) database and were grouped by whether PORT was administered. Survival analysis was used to identify the patient groups who can benefit from PORT. Multivariate analysis was performed to confirm the independent risk factors for lung cancer‐specific survival (LCSS) and overall survival (OS). A validation cohort of 1184 patients from three medical centers in China were also included.ResultsPORT was not associated with better LCSS and OS in the entire cohort after propensity score matching (PSM). However, in the subgroups of positive lymph nodes 4 (PLN4), lymph node ratio 4 (LNR4), and log odds of positive lymph nodes 4 (LODDS4), PORT exhibited its role in improving LCSS (p < 0.05). Although the three nodal classifications were all identified as independent predictors of LCSS and OS, LODDS classification had the best discriminatory ability and prognostic accuracy for stage IIIA‐N2 patients. Similar results were also obtained in the validation cohort.ConclusionsThe LODDS classification not only exhibited the best prognostic performance in predicting LCSS and OS in stage IIIA‐N2 disease, but also could help tailor individualized PORT.

Spleen transient elastography predicts actuarial survival after liver transplantation.

Splenic transient elastography (TE) correlates with increased portal pressure. Little data are available in the post liver transplantation (LTx) setting. Three months after LTx, we performed splenic TE in 125 LTx recipients. Mean splenic TE values were 29.4 (±6.3; range, 21.6-49.2) kPa. Splenic TE correlated with reduced time to development until persistent ascites (30 events, OR =1.082, 95% CI: 1.034-1.133; P=0.001), hepatorenal syndrome (8 events, OR =1.109, 95% CI: 1.015-1.211; P=0.022) and hepatic encephalopathy (16 events, OR =1.136, 95% CI: 1.066-1.211; P=0.000). In Cox univariate analysis, splenic TE served as a predictor of actuarial survival free of liver (OR =1.114, 95% CI: 1.050-1.182; P<0.001) and remained an independent risk factor associated with reduced actuarial survival free of LTx in multivariate analysis (OR =1.103, 95% CI: 1.026-1.186; P=0.008). Splenic TE measurement at 3 months after LTx serves as a robust predictor of survival in LTx recipients.

Clinical and laboratory characteristics and prognosis of patients with hepatocellular carcinoma

Purpose: We investigated the influence of baseline characteristics of patients with hepatocellular carcinoma (HCC) on prognosis. Methods: A Retrospective descriptive study on patients with HCC was carry out at the Oncology Department of Hue University of Medicine and Pharmacy Hospital and Hue Central Hospital (HCH), Viet Nam, from Oct 2015 to Dec 2019. Demographic, laboratory, tumor characteristics, and performance status were determined before treatment. Predictors of survival were identified using the Kaplan - Meir test and the Cox model. Result: A total of 261 patients, 87.4% male; median age was 58.4; 80,1% of patients admitted to hospital because of right upper quadrant pain. 45.2% ECOG 0, 51.7% ECOG 1; AFP &gt; 400 ng/mlhas 67.4%. The most robust predictors of survival were tumor size, ECOG, portal vein tumor thrombus, Barcelona Clinic Liver Cancer (BCLC), initial treatment. Overall survival in patients with HCC was 9.0 months. In a multivariate analysis: BCLC and initial treatment modalities were independent predictors of survival. Conclusions - Patients with HCC had a poor survival with a median of nine months. Five easily measurable clinical variables were significant predictors of survival in patients with HCC.

Impact of geriatric assessment (GA) based frailty index (CARE-Frailty Index) on mortality and treatment-related toxicity among older adults with gastrointestinal (GI) malignancies.

12046 Background: Older adults with cancer are at increased risk of treatment-related toxicity and mortality. A comprehensive geriatric assessment (GA) may uncover aging associated vulnerability and identify those at greatest risk of adverse outcomes. We studied the association between a novel frailty index and treatment-related morbidity and mortality among older adults with GI malignancies. Methods: Older adults (≥60y) referred for initial consultation at the UAB GI oncology clinic between 9/2017 to 12/2020 were enrolled in a prospective Cancer and Aging Resilience Evaluation (CARE) registry. All participants underwent a patient-reported GA at baseline as previously described (Williams et al J Geriat Oncol 2020). Using this information, we constructed a 44-item frailty index using a deficit accumulation approach. Vital status was acquired by linking with death records and chart review. In a subgroup of patients continuing care at UAB, we collected information on toxicity for the first 6 months of treatment via chart review using CTCAE v5.0. We used Kaplan Meier Methods and log-rank test to compare survival distributions, and a multivariate cox regression to adjust for potential confounders. We compared the toxicity rates across frailty subgroups using risk ratio (RR) calculated from general linear models. Results: Of 765 consecutive older adults referred to GI oncology clinic, 590 (77%) had available data to measure frailty index. Median age at enrollment was 68y; with 59% males and 72% White. Common cancer types included colorectal (30%) and pancreatic cancer (26%); mostly with advanced stage disease (stage III 28%; IV 46%). Overall, 168 (28%) were characterized as pre-frail and 230 (39.3%) as frail. As compared to non-frail, those who were frail were more likely to be Black (33% vs 20%; p &lt; 0.01) and have pancreatic cancer (33.6% vs 21.8%; p &lt; 0.01). Over a median follow up of 22 months, 212 (36%) patients had died. The 2y overall survival among non-frail, pre-frail and frail patients was 71%, 63% and 51%, respectively (log rank p value &lt; 0.001). In a multivariate cox regression, as compared to non-frail patients, frailty was associated with worse OS (HR 1.75; 95% CI 1.13-2.70; p = 0.01) after adjusting for age, sex, race, cancer stage, cancer type, line of therapy and performance status. In a subset of 168 patients with available data, baseline frailty was associated with increased risk of ≥grade 3 non-hematologic toxicity (RR 2.23; 95% CI 1.27-3.92; p &lt; 0.01) but not ≥grade 3 hematologic toxicity (RR 1.03; 95% CI 0.67-1.58; p = 0.90) as compared to non-frail patients Conclusions: The CARE-Frailty Index is a novel frailty index built on the principle of deficit accumulation using a patient-reported GA, and appears to be a robust predictor of survival and may predict treatment related toxicity among older adults with GI malignancies.

HDL-related biomarkers are robust predictors of survival in patients with chronic liver failure

High-density lipoprotein cholesterol (HDL-C) levels are reduced in patients with chronic liver disease and inversely correlate with disease severity. During acute conditions such as sepsis, HDL-C levels decrease rapidly and HDL particles undergo profound changes in their composition and function. We aimed to determine whether indices of HDL quantity and quality associate with progression and survival in patients with advanced liver disease. HDL-related biomarkers were studied in 508 patients with compensated or decompensated cirrhosis (including acute-on-chronic liver failure [ACLF]) and 40 age- and gender-matched controls. Specifically, we studied levels of HDL-C, its subclasses HDL2-C and HDL3-C, and apolipoprotein A1 (apoA-I), as well as HDL cholesterol efflux capacity as a metric of HDL functionality. Baseline levels of HDL-C and apoA-I were significantly lower in patients with stable cirrhosis compared to controls and were further decreased in patients with acute decompensation (AD) and ACLF. In stable cirrhosis (n= 228), both HDL-C and apoA-I predicted the development of liver-related complications independently of model for end-stage liver disease (MELD) score.In patients with AD, with or without ACLF (n= 280), both HDL-C and apoA-I were MELD-independent predictors of 90-day mortality. On ROC analysis, both HDL-C and apoA-I had high diagnostic accuracy for 90-day mortality in patients with AD (AUROCs of 0.79 and 0.80, respectively, similar to that of MELD 0.81). On Kaplan-Meier analysis, HDL-C <17 mg/dl and apoA-I <50 mg/dl indicated poor short-term survival. The prognostic accuracy of HDL-C was validated in a large external validation cohort of 985 patients with portal hypertension due to advanced chronic liver disease (AUROCs HDL-C: 0.81 vs. MELD: 0.77). HDL-related biomarkers are robust predictors of disease progression and survival in chronic liver failure. People who suffer from cirrhosis (scarring of the liver) have low levels of cholesterol carried by high-density lipoproteins (HDL-C). These alterations are connected to inflammation, which is a problem in severe liver disease. Herein, we show that reduced levels of HDL-C and apolipoprotein A-I (apoA-I, the main protein carried by HDL) are closely linked to the severity of liver failure, its complications and survival. Both HDL-C and apoA-I can be easily measured in clinical laboratories and are as good as currently used prognostic scores calculated from several laboratory values by complex formulas.

Routine Liver Elastography Could Predict Actuarial Survival after Liver Transplantation.

Transient elastography (TE) has routinely been implemented in the diagnosis and assessment of chronic liver disease. Little data are available in the post liver transplant (LTx) setting. Three months after LTx, we performed TE in 137 liver transplant recipients and investigated its predictive value upon further clinical outcome. The mean follow-up time for clinical outcome was 24 months. Mean TE value was 10.6 kPa (± 6.3 kPa; range 2.8 - 29.9 kPa). There was a significant correlation between TE and aspartate aminotransferase (AST) (p=0.004), gamma-glutamyl transferase (GGT) (p=0.031) and bilirubin (p<0.001) serum levels. In Cox univariate analysis, TE served as a predictor of actuarial survival free of liver transplantation (OR=1.111, 95%CI: 1.051-1.174; p<0.001). In multivariate analysis, TE remained an independent risk factor associated with reduced actuarial survival free of liver transplantation (OR=1.080, 95%CI: 1.001-1.166; p=0.047), along with thrombocytes (OR=0.992, 95%CI: 0.986-0.999; p=0.020) and metabolic co-disease (OR = 0.250, 95%CI: 0.070-0.895; p=0.033). Transient elastography measurement at three months after LTx seems a robust predictor of survival in liver transplant recipients.

Metabolic tumor burden on baseline 18F-FDG PET/CT improves risk stratification in pediatric patients with mature B-cell lymphoma.

In order to better identify patients most at risk of treatment failure and disease progression in pediatric mature B-cell non-Hodgkin lymphoma (B-NHL), the prognostic role of metabolic tumor burden measured on baseline 18F-FDG PET/CT scan, including total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG), was investigated. Pretreatment 18F-FDG PET/CT scans from 46 consecutive pediatric patients (median age 7years; range 2-18years) with newly diagnosed B-NHL were retrospectively analyzed. Clinicopathological parameters and imaging characteristics, including TMTV, TLG, and bone marrow (BM) involvement detected by PET/CT were compared to predict progression-free survival (PFS) and overall survival (OS). The median follow-up time was 31months. Areas under the curve of TMTV and TLG to predict events were 0.820 and 0.816, respectively. The 2-year PFS and OS were 29% and 43% in 7 patients with high TLG (> 5797g) vs. 93% and 96% in those with low TLG (P < 0.001). High TMTV (> 524cm3) was present in ten patients and predicted a significantly inferior outcome (PFS: 50% vs. 92%, P = 0.001; OS: 60% vs. 96%, P = 0.002). In multivariate analysis, TMTV and TLG outperformed other clinicopathological factors, including serum lactate dehydrogenase and BM involvement on biopsy, and remained the most robust predictors of survival. Furthermore, TLG sub-stratified patients with distinct outcomes efficiently within high- or intermediate-risk groups, with the negative predictive value of 100% and 92% and the positive predictive value of 100% and 50% for high-risk and intermediate-risk patients, respectively. On the other hand, BM involvement identified only by PET demonstrated an inferior prognostic value in comparison with BM biopsy. Baseline TMTV and TLG are both strong independent prognostic factors for pediatric B-NHL and provide a potential approach to aid in risk sub-stratification, especially in patients with high-risk disease.

A Paradoxical Correlation of Cancer-Associated Fibroblasts With Survival Outcomes in B-Cell Lymphomas and Carcinomas.

The tumor microenvironment is increasingly recognized as an active participant in tumor progression. A recent pan-cancer genomic profile analysis has revealed that gene signatures representing components of the tumor microenvironment are robust predictors of survival. A stromal gene signature representing fibroblasts and extracellular matrix components has been associated with good survival in diffuse large B-cell lymphoma (DLBCL). Paradoxically, a closely related gene signature has been shown to correlate with poor survival in carcinomas, including breast, ovarian, pancreatic, and colorectal cancer. To date, there has been no explanation for this paradoxical inverse correlation with survival outcomes in DLBCL and carcinomas. Using public gene data sets, we confirm that the DLBCL stromal gene signature is associated with good survival in DLBCL and several other B-cell lymphomas while it is associated with poor survival in ovarian cancer and several other solid tumors. We show that the DLBCL stromal gene signature is enriched in lymphoid fibroblasts in normal lymph nodes and in cancer-associated fibroblasts (CAFs) in ovarian cancer. Based on these findings, we propose several possible mechanisms by which CAFs may contribute to opposite survival outcomes in B-cell lymphomas and carcinomas.

Expression of COBLL1 encoding novel ROR1 binding partner is robust predictor of survival in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia is a disease with up-regulated expression of the transmembrane tyrosine-protein kinase ROR1, a member of the Wnt/planar cell polarity pathway. In this study, we identified COBLL1 as a novel interaction partner of ROR1. COBLL1 shows clear bimodal expression with high levels in chronic lymphocytic leukemia patients with mutated IGHV and approximately 30% of chronic lymphocytic leukemia patients with unmutated IGHV. In the remaining 70% of chronic lymphocytic leukemia patients with unmutated IGHV, COBLL1 expression is low. Importantly, chronic lymphocytic leukemia patients with unmutated IGHV and high COBLL1 have an unfavorable disease course with short overall survival and time to second treatment. COBLL1 serves as an independent molecular marker for overall survival in chronic lymphocytic leukemia patients with unmutated IGHV. In addition, chronic lymphocytic leukemia patients with unmutated IGHV and high COBLL1 show impaired motility and chemotaxis towards CCL19 and CXCL12 as well as enhanced B-cell receptor signaling pathway activation demonstrated by increased PLCγ2 and SYK phosphorylation after IgM stimulation. COBLL1 expression also changes during B-cell maturation in non-malignant secondary lymphoid tissue with a higher expression in germinal center B cells than naïve and memory B cells. Our data thus suggest COBLL1 involvement not only in chronic lymphocytic leukemia but also in B-cell development. In summary, we show that expression of COBLL1, encoding novel ROR1-binding partner, defines chronic lymphocytic leukemia subgroups with a distinct response to microenvironmental stimuli, and independently predicts survival of chronic lymphocytic leukemia with unmutated IGHV.

Tumour heterogeneity in glioblastoma assessed by MRI texture analysis: a potential marker of survival.

The main objective of this retrospective work was the study of three-dimensional (3D) heterogeneity measures of post-contrast pre-operative MR images acquired with T1 weighted sequences of patients with glioblastoma (GBM) as predictors of clinical outcome. 79 patients from 3 hospitals were included in the study. 16 3D textural heterogeneity measures were computed including run-length matrix (RLM) features (regional heterogeneity) and co-occurrence matrix (CM) features (local heterogeneity). The significance of the results was studied using Kaplan-Meier curves and Cox proportional hazards analysis. Correlation between the variables of the study was assessed using the Spearman's correlation coefficient. Kaplan-Meyer survival analysis showed that 4 of the 11 RLM features and 4 of the 5 CM features considered were robust predictors of survival. The median survival differences in the most significant cases were of over 6 months. Heterogeneity measures computed on the post-contrast pre-operative T1 weighted MR images of patients with GBM are predictors of survival. Texture analysis to assess tumour heterogeneity has been widely studied. However, most works develop a two-dimensional analysis, focusing only on one MRI slice to state tumour heterogeneity. The study of fully 3D heterogeneity textural features as predictors of clinical outcome is more robust and is not dependent on the selected slice of the tumour.

Metastatic Spinal Cord Compression from Non-Small-Cell Lung Cancer Treated with Surgery and Adjuvant Therapies: A Retrospective Analysis of Outcomes and Prognostic Factors in 116 Patients.

Metastatic spinal cord compression is a disastrous consequence of non-small-cell lung cancer (NSCLC). There have been few studies of the outcomes or prognostic factors in patients with metastatic spinal cord compression from NSCLC treated with surgery and adjuvant therapies. From 2002 to 2013, 116 patients with metastatic spinal cord compression from NSCLC treated with surgery and adjuvant therapies were enrolled in this retrospective analysis. Kaplan-Meier methods and Cox regression analysis were used to estimate overall survival and identify prognostic factors for survival. Multivariate analysis suggested that the Eastern Cooperative Oncology Group performance status (ECOG-PS), preoperative and postoperative Frankel scores, postoperative adjuvant radiation therapy, and target therapy were independent prognostic factors. Ninety patients died at a median of twelve months (range, three to forty-seven months) postoperatively, and twenty-six patients were still alive at the time of final follow-up (at a median of fifteen months [range, five to fifty-four months]). The complete disappearance of deficits in spinal cord function after surgery was the most robust predictor of survival. Adjuvant radiation therapy and target therapy were also associated with a better prognosis. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Sentinel lymph node biopsy is prognostic but not therapeutic for thick melanoma

Sentinel lymph node biopsy (SNB) as a staging and therapeutic procedure in melanomas 1-4mm in thickness has been investigated extensively, however, the clinical value of SNB in thick melanomas is poorly understood. Patients undergoing operation for clinically node-negative melanoma >4mm in depth between 2003 and 2010 were identified in the Surveillance Epidemiology and End Results registry. Two groups were constructed: one with a wide excision with SNB and the other with wide excision alone. A total of 4,571 patients with clinically node-negative, thick melanoma were identified. The median age was 71years, 96.9% were white, and 64.3% were male. SNB was performed in 2,746 (60.1%) and was positive in 32.2%. Univariate analysis demonstrated SNB was associated with younger age (64 vs 75years; P<.001) and extremity primaries (P<.0001). On logistic regression, advanced age (P<.001), female sex (P=.009), and location in the head and neck region (P<.001) were associated with observation. On log-rank analysis, improved 5-year disease-specific survival (DSS) was associated with SNB (65 vs 62%; P=.008), location in the extremity versus head and neck or trunk (67 vs 61.5 and 60.3%; P=.004), female sex (69 vs 61%; P<.001), and no ulceration (74 vs 54%; P<.001). On Cox regression analysis, advanced age (P<.001), male sex (P=.01), trunk location (P=.0001), and ulceration (P<.001) continued to be associated with DSS. SNB was not associated with survival (P=.20). SNB status was a robust predictor of survival; a negative SNB had a 5-year DSS of 75.3 versus 44.1% (P<.0001), with a positive node. For patients with clinically node-negative, thick melanoma, SNB is a staging but not therapeutic procedure.

Decline in CA19-9 during chemotherapy predicts survival in four independent cohorts of patients with inoperable bile duct cancer

BackgroundCarbohydrate associated antigen (CA19-9) has been approved by the FDA as a biomarker for monitoring treatment effect in pancreatic cancer. However, the value of serum CA19-9 as a biomarker of response to chemotherapy in bile duct cancer is unclear. The aim of this study was to determine if a decline in CA19-9 (CA19-9 response) during chemotherapy is predictive of survival in patients with inoperable bile duct cancer. MethodsConsecutive patients with inoperable bile duct cancer treated at a University Hospital were retrospectively included in an investigational cohort (n=212). Three validation cohorts were established including patients 1) participating in phase I/II trials at a Danish Hospital (n=71), 2) identified retrospectively in a Canadian cohort (n=196) and 3) randomized in the ABC-02 trial (n=410). Patients with a baseline CA19-9 and at least one CA19-9 value measured 10-12 weeks after the start of chemotherapy were included. Multivariate Cox regression analyses were performed. ResultsPatients meeting the criteria to be included were 54 in the investigational cohort and 34, 68 and 148 in the three validation sets, respectively. Multivariate analysis included radiological response, performance status, bilirubin, gender, site of cancer, extend of disease, CA19-9 at baseline and age. A hazard ratio (HR) of 0.60 (95%CI: 0.44-0.80, p=0.0005) for death in CA19-9 responders was reached in the investigational cohort. The predictive value of CA 19-9 response was confirmed in all three validation cohorts. ConclusionsCA19-9 response is a robust predictor of survival in patients with inoperable bile duct cancer in four independent data sets.

Multicenter Analysis of Very Elderly Indolent and Aggressive Non-Hodgkin Lymphoma (NHL): Impact of Functional Status on Outcome,

Abstract 3668 Background:The prevalence of NHL in patients (pts) ≥ 80 years has recently tripled; however, data on prognostic factors and treatment for this very elderly population is sparse. Methods:A multicenter retrospective analysis of NHL pts ≥80 years diagnosed between (1999–2009) was completed. Detailed characteristics obtained include geriatric syndromes (GS), activities of daily living (ADLs), and co-morbidities using the Cumulative Illness Rating Scale-Geriatrics (CIRS-G). Further, univariate associations with survival were determined, while a multivariate Cox regression proportional hazards model was performed. Results:We identified 303 pts: 170 aggressive NHL (84% B-cell and 16% T-cell) and 133 indolent NHL (82% B-cell and 18% T-cell). Median age was 84 years (range 80–95). Poor performance status (PS), high LDH, and extranodal disease were more common in aggressive vs. indolent NHLs (P=0.004, 0.005, and 0.002, respectively). Furthermore, aggressive NHL pts presented more frequently with advanced stage and higher relative prognostic scores (P=0.0002 and 0.003 respectively). Loss of any ADL was more frequent in aggressive histology (P=0.002). Diffuse large B-cell NHL was the most common histology overall, while follicular lymphoma was the most diagnosed indolent NHL. At least one GS was present in 80 pts (26%) with dementia being most common (26%). Loss of at least one ADL was seen in 14%, while 30% of pts were considered “non-fit” at diagnosis. Of available treatment data in aggressive B-NHL, 62% received rituximab (R)-containing regimen and 18% received chemotherapy without R. Those with aggressive T-cell NHL were treated with systemic therapy in 74%, topical in 15%, radiation in 4%, and no therapy in 7%. Indolent B-cell NHL had observation in 38% for a median of 26 months, R alone in 21%, R plus chemotherapy in 15%, radiation alone in 7%, and chemotherapy alone in 9%. Cutaneous T-cell pts received topical therapies in 42%, systemic therapy in 29%, and radiation alone in 17%. At 49-month median follow-up, 4-year progression-free (PFS) and overall survival (OS) for aggressive NHL were 31% and 44%, respectively (stage I/II: PFS 53% and OS 66%; stage III/IV: PFS 20% and OS 32%; p<0.0001 and 0.0002, respectively). Four-year PFS and OS for indolent NHL were 44% and 66%, respectively, regardless of stage. Prognostic factors predicting OS and PFS on univariate are detailed in Table 1. Cox multivariate regression analysis identified two factors predicting inferior outcome for both NHL groups: lack of complete response (CR) (indolent: PFS, P=0.03; OS, P=0.01; aggressive: PFS, P<0.0001; OS, P<0.0002) and loss of ADLs (indolent: PFS, P=0.003; OS, P=0.0004; aggressive: PFS, P=0.002; OS, P<0.0001).Table 1Prognostic factors associated with survival (univariate analysis)Aggressive NHLPFSOSHR95% CIPHR*95% CIPECOG PS 2-41.69(1.12, 2.56)0.012.35(1.48, 3.73)0.0003Any CIRS score 41.42(0.91, 2.22)0.121.99(1.24, 3.19)0.004Loss of any ADL2.89(1.86, 4.50)<0.00013.57(2.53, 5.66)<0.0001Any geriatric syndrome1.31(0.88, 1.96)0.181.77(1.17, 2.69)0.007Elevated creatinine1.51(0.99, 2.30)0.0531.67(1.08, 2.58)0.02Elevated LDH1.55(1.05, 2.27)0.031.68(1.10, 2.57)0.02Hypoalbuminemia1.15(0.99, 1.34)0.071.35(1.15, 1.58)0.0003Stage III/IV2.40(1.54, 3.74)0.00012.49(1.52, 4.08)0.0003Marrow involvement1.93(1.22, 3.06)0.0051.60(0.98, 2.61)0.06↑ IPI or FLIPI1.91(1.26, 2.90)0.0022.26(1.43, 3.57)0.0005Response: no CR2.88(1.91, 4.32)<0.00012.35(1.51, 3.67)0.0002Indolent NHLPFSOSHR*95% CIPHR*95% CIPLoss of any ADL3.58(1.61, 7.96)0.0025.56(2.27, 13.61)0.0002Any geriatric syndrome1.86(1.13, 3.05)0.011.69(0.97, 2.94)0.06B symptoms1.34(0.64, 2.81)0.452.11(0.98, 4.54)0.055Weight loss >10%1.28(0.67, 2.48)0.452.81(1.43, 5.52)0.003ECOG PS 2-41.14(0.84, 1.54)0.401.36(1.01, 1.83)0.045Response: no CR2.19(1.18, 4.05)0.012.91(1.37, 6.20)0.006 Conclusion:To our knowledge, this represents the largest analysis of very elderly NHL reported to date. We identified that loss of ADL's and lack of CR to initial treatment were robust predictors of survival in very elderly NHL, irrespective of histology, and they superseded the prognostic value of either PS or age. Geriatric assessments, including ADLs, are powerful predictors of outcome in very elderly NHL and should be prospectively studied. Disclosures:No relevant conflicts of interest to declare.

Presentation and outcomes of hepatocellular carcinoma patients at a western centre

BackgroundThe present study examines the presentation and outcomes of hepatocellular carcinoma (HCC) at a Western centre over the last decade. MethodsBetween January 2000 and September 2009, 1010 patients with HCC were evaluated at the University of Pittsburgh Medical Center (UPMC). Retrospectively, four treatment groups were classified: no treatment (NT), systemic therapy (ST), hepatic artery-based therapy (HAT) and surgical intervention (SI) including radiofrequency ablation, hepatic resection and transplantation. Kaplan–Meier analysis assessed survival between groups. Cox regression analysis identified factors predicting survival. ResultsPatients evaluated were 75% male, 87% Caucasian, 84% cirrhotic, and predominantly diagnosed with hepatitis C. In all, 169 patients (16.5%) received NT, 25 (2.4%) received ST, 529 (51.6%) received HAT and 302 (29.5%) received SI. Median survival was 3.6, 5.6, 8.8, and 83.5 months with NT, ST, HAT and SI, respectively (P= 0.001). Transplantation increased from 9.5% to 14.2% after the model for end-stage liver disease (MELD) criteria granted HCC patients priority points. Survival was unaffected by bridging transplantation with HAT or SI (P= 0.111). On multivariate analysis, treatment modality was a robust predictor of survival after adjusting for age, gender, AFP, Child–Pugh classification and cirrhosis (P < 0.001, χ2= 460). DiscussionMost patients were not surgical candidates and received HAT alone. Surgical intervention, especially transplantation, yields the best survival.

Marital Trajectories and Mortality Among US Adults

More than a century of empirical evidence links marital status to mortality. However, the hazards of dying associated with long-term marital trajectories and contributing risk factors are largely unknown. The authors used 1992-2006 prospective data from a cohort of US adults to investigate the impact of current marital status, marriage timing, divorce and widow transitions, and marital durations on mortality. Multivariate hazard ratios were significantly higher for adults currently divorced and widowed, married at young ages (< or =18 years), who accumulated divorce and widow transitions (among women), and who were divorced for 1-4 years. Results also showed significantly lower risks of mortality for men married after age 25 years compared with on time (ages 19-25 years) and among women experiencing > or =10 years of divorce and > or =5 years of widowhood relative to those without exposure to these statuses. For both sexes, accumulation of marriage duration was the most robust predictor of survival. Results from risk-adjusted models indicated that socioeconomic resources, health behaviors, and health status attenuated the associations in different ways for men and women. The study demonstrates that traditional measures oversimplify the relation between marital status and mortality and that sex differences are related to a nexus of marital experiences and associated health risks.