Vitamin D status and survival of metastatic colorectal cancer patients: Results from CALGB/SWOG 80405 (Alliance).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 507-507 ◽  
Author(s):  
Kimmie Ng ◽  
Alan P. Venook ◽  
Kaori Sato ◽  
Bruce W. Hollis ◽  
Donna Niedzwiecki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Prognostic Factors ◽  
Proportional Hazards ◽  
Performance Status ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Sensitivity Analyses ◽  
Blood Draw ◽  
Ecog Performance Status

507 Background: Prospective epidemiologic data suggest that higher levels of 25-hydroxyvitamin D [25(OH)D] are associated with improved survival in patients with colorectal cancer (CRC), however, the relationship between 25(OH)D and outcome in metastatic CRC, specifically, is unknown. Methods: We prospectively assessed the association between plasma 25(OH)D and overall survival (OS) in previously untreated metastatic CRC patients enrolled in CALGB 80405, a randomized phase III trial of chemotherapy + bevacizumab, cetuximab, or both, prior to the KRAS WT amendment. Progression-free survival (PFS) was a secondary endpoint. Plasma 25(OH)D levels were measured at baseline by radioimmunoassay, and dietary and lifestyle behaviors collected from self-administered questionnaires. Cox proportional hazards models were used to calculate hazard ratios adjusted for other prognostic factors. In sensitivity analyses, patients who died within 3 or 6 months of blood draw were excluded to address the possibility of reverse causation. Results: Among 1,043 patients, median plasma 25(OH)D was 17.2 ng/mL (range 2.2-72.7). Older and black patients, those with lower dietary and supplemental vitamin D intake, ECOG performance status 1 (vs. 0), higher body-mass index, lower physical activity, and blood draws during the winter and spring had significantly lower levels of 25(OH)D. Patients in the highest quintile of 25(OH)D had significantly improved OS compared to those in the lowest after adjusting for pathologic and clinical prognostic factors (median 32.6 vs. 24.5 months; HR 0.67, 95% CI, 0.53-0.86; p trend 0.002). Increasing concentrations of 25(OH)D were also associated with improved PFS (median 12.2 vs. 10.1 months; HR 0.80, 95% CI, 0.64-1.01; p trend = 0.02). The results were consistent across subgroups of patient characteristics, including KRAS status, and remained unchanged after excluding patients who died within 3 or 6 months of blood draw. Conclusions: Higher concentrations of plasma 25(OH)D are associated with significantly improved survival in metastatic CRC patients treated with chemotherapy + biologics. Randomized trials of vitamin D supplementation are warranted and are currently underway.

A phase III randomized intergroup trial (S0016) comparing CHOP plus rituximab with CHOP plus iodine-131-tositumomab for front-line treatment of follicular lymphoma: Results of subset analyses and a comparison of prognostic models.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8001-8001
Author(s):  
Oliver W. Press ◽  
Joseph M Unger ◽  
Michael Leo LeBlanc ◽  
Lisa M. Rimsza ◽  
Jonathan W. Friedberg ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Prognostic Factors ◽  
Proportional Hazards ◽  
Performance Status ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Prognostic Models ◽  
Prognostic Impact ◽  
Prior Therapy ◽  
Follicular Lymphomas

8001 Background: Advanced follicular lymphomas (FL) are considered incurable with chemotherapy and there is no consensus on the best treatment. Outcomes are variable, but can be partially predicted by defined prognostic factors. SWOG and CALGB compared the safety and efficacy of 2 immunochemotherapy regimens in a Phase III trial enrolling 554 patients between 3/1/2001 and 9/15/2008. Methods: Patients were eligible if they had bulky stage II, III or IV FL and had not received prior therapy. Patients randomized to CHOP-R received 6 cycles of CHOP every 21 days + 6 doses of rituximab. Patients randomized to CHOP-RIT received 6 cycles of CHOP, followed by consolidative radioimmunotherapy with tositumomab/iodine I-131 tositumomab. A Cox proportional hazards multi-variable regression analysis assessed the prognostic impact of age, stage, LDH, LN size and number, performance status, hemoglobin, β2 microglobulin, BM involvement, and B symptoms.  The prognostic value of 3 multi-variable models were compared. Results: Outcomes were outstanding with either CHOP-R or CHOP-RIT (2 yr PFS: 76% vs 80% [ p =0.11]; 2 yr OS: 97% vs 93% [p =0.08], respectively).  Subset analyses so far have not identified any subgroups clearly benefitting to a greater degree from CHOP-R or CHOP-RIT in terms of both PFS and OS. Cox multivariable regression analysis identified serum-β2M, LDH level, and FLIPI index as the strongest prognostic factors associated with worse PFS and OS. Conclusions: Both regimens produced outstanding PFS and OS, and no statistically significant differences between them were observed.  FLIPI, FLIPI2, and LDH + β2M models were all strong predictors of patient outcomes.  A combination of LDH + β2M was as good as the FLIPI index, and was simpler to apply.  (Supported in part by NCI grants CA32102 and CA38926 from the NCI and GlaxoSmithKline.) [Table: see text]

Comparison of outcomes with pembrolizumab monotherapy (P) versus combination with chemotherapy (P+C) in advanced non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21579-e21579
Author(s):  
Kartik Sehgal ◽  
Ritu R. Gill ◽  
Poorva Bindal ◽  
Anita Geevarghese Koshy ◽  
Danielle C McDonald ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Advanced Nsclc ◽  
Proportional Hazards Model ◽  
Smoking Status ◽  
Performance Status ◽  
Objective Response ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Phase Iii ◽  
Ecog Performance Status

e21579 Background: P and P+C are standard-of-care (SOC) treatment options for advanced NSCLC. However, they have not yet been directly compared in clinical trials. Methods: We conducted a retrospective cohort study of patients with advanced NSCLC who initiated treatment with SOC P±C at our center from 2/11/16 to 10/15/19 (data cutoff 1/15/20). Patient demographic, clinicopathologic, therapeutic and outcomes data were extracted. All radiographic scans were independently evaluated by a thoracic radiologist using iRECIST. Survival time was defined from the start of P±C. Kaplan-Meier and Cox proportional hazards model were utilized. Results: Of 103 patients with median follow up of 17.7 months, 74 (71.8%) had received P, while 29 (28.2%) had received P+C. In PD-L1 tumor proportion score (TPS) unselected population, there were no significant differences in age, sex, smoking status, driver mutation, tumor mutational burden (TMB), line of therapy, ECOG performance status (PS) or immune-related adverse events (irAE) between P and P+C groups. 71.6% in P vs 13.8% in P+C had PD-L1 TPS ≥50% (p < 0.001). There were no significant differences between the two groups in objective response rate (ORR), disease control rate (DCR), unadjusted progression-free survival (PFS) or unadjusted overall survival (OS) (Table). Multivariable adjustment for confounding factors between P+C vs P revealed no differences in OS [hazard ratio (HR) for death, 1.53, 95% CI 0.55 – 4.25] or PFS [HR for progression/death, 1.75, 95% CI 0.63 – 4.91]. Further stratification into PD-L1 TPS ≥50% and < 50% showed no significant differences between P+C vs. P in adjusted OS [HR for death, TPS < 50%- 1.54 (95% CI 0.59 – 4.03); TPS ≥50%- 0.71 (95% CI 0.11 – 4.52)] or PFS [HR for progression/death, TPS < 50%- 1.58 (95% CI 0.72 – 3.48); TPS ≥50%- 0.64 (95% CI 0.06 – 6.93)]. ECOG PS and development of irAE influenced OS in all groups, while TMB was relevant in PD-L1 ≥50% only. Conclusions: Our study shows no significant differences in outcomes with P vs P+C in advanced NSCLC in a real-world setting, albeit with limitations of single-center design, limited sample size, different line settings and lack of disease burden stratification. Ongoing phase III trials comparing front line P vs P+C will definitively address the long-term clinical benefits -if any- of combining cytotoxic chemotherapy with anti-PD-1 drugs. [Table: see text]

Timeliness of adjuvant chemotherapy in patients with resected pancreatic cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18038-e18038
Author(s):  
David Deng ◽  
Winson Y. Cheung
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Adjuvant Chemotherapy ◽  
Proportional Hazards ◽  
Performance Status ◽  
Population Based ◽  
Cox Proportional Hazards ◽  
Study Cohort ◽  
Ecog Performance Status

e18038 Background: Timeliness of adjuvant chemotherapy is an important predictor of survival for patients with breast and colorectal cancer whereby long delays has been shown to detrimentally impact outcomes. The effects of adjuvant treatment timing remain largely unknown for early pancreatic cancer. This study aims to identify independent predictors of treatment timeliness and overall survival in this patient population. Methods: We conducted a retrospective, population-based analysis of 179 patients with resected pancreatic cancer who subsequently started adjuvant chemotherapy between 2008 and 2014 at any 1 of 6 cancer centers across British Columbia, Canada. Logistic regression was used to identify predictive factors for adjuvant chemotherapy timing. Prognostic factors for survival were ascertained using multivariate Cox proportional hazards models. Results: Our study cohort included 91 men (51%) and 88 women (49%). At time of diagnosis, 145 patients (81%) had nodal involvement and 107 patients (60%) had good ECOG performance status (ECOG 0-1). The median age of diagnosis was 67 (range 37-85) years. The median interval between surgery and start of adjuvant chemotherapy was 70 (range 19-46) days. Abnormal bilirubin was the only factor significantly correlated with delayed chemotherapy (OR, 3.89; 95% CI, 1.55-9.73; P = 0.004). Median overall survival was 468 days following resection (95% CI, 425-538). Multivariate survival analysis showed that high CA 19-9 levels (HR, 2.44, 95% CI: 1.36-4.40, P = 0.003) and abnormal bilirubin (HR, 0.40; 95% CI, 0.22-0.73; P = 0.003) were prognostic factors for overall survival. Median survival for patients who waited up to 35, 70 or 105 days for chemotherapy following resection were 588 days (95% CI, 270-776), 490 days (95% CI, 360-688) and 466 days (95% CI, 432-538) respectively. Overall, timeliness was not predictive of survival (HR, 1.12; 95% CI, 0.64-1.97; P= 0.70). Conclusions: Patients with hyperbilirubinema experienced delays in adjuvant chemotherapy, likely due to the need for relief of biliary obstruction and subsequent recovery. However, timeliness of adjuvant chemotherapy did not influence outcomes, suggesting that treatment should still be considered irrespective of timing.

Body weight loss (BWL) as a prognostic/predictive factor in previously treated patients (pts) with metastatic gastric or gastroesophageal junction cancer (mGC/GEJC): Post-hoc analyses of the phase III tags trial.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 476-476
Author(s):  
Michele Ghidini ◽  
Howard S. Hochster ◽  
Toshihiko Doi ◽  
Eric Van Cutsem ◽  
Lukas Makris ◽  
...  
Keyword(s):  
Body Weight ◽  
Prognostic Factors ◽  
Proportional Hazards ◽  
Cox Model ◽  
Gastroesophageal Junction ◽  
Body Weight Loss ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Body Weight Data ◽  
Grade 3

476 Background: Nutritional status is closely linked to cancer mortality, and BWL has been shown to be prognostic for survival in curative, first-, and second-line settings in mGC/GEJC. In the phase III TAGS trial, trifluridine/tipiracil (FTD/TPI) showed clinical benefit versus placebo (PBO) and manageable safety in pts with mGC/GEJC who had received ≥2 prior chemotherapy regimens. The association of early BWL with survival outcomes in TAGS was examined in retrospective analyses. Methods: The TAGS intent-to-treat (ITT) population was categorized into pts who experienced <3% or ≥3% BWL from the start of treatment until day 1 of cycle 2 (each cycle: 28 days). Overall survival (OS), and progression-free survival (PFS) were compared between subgroups within each treatment arm due to significant imbalances of early BWL between treatment arms. The effect of early BWL on OS was assessed by a univariate Cox proportional hazards (PH) model as well as a multivariate Cox PH model that adjusted for baseline prognostic factors identified in the original ITT analysis. Results: Body weight data were available for 451 of 507 (89%) pts in the study (n=304, FTD/TPI; n=147, PBO). In the FTD/TPI and PBO arms, respectively, 74% (224/304 pts) and 65% (95/147) experienced <3% BWL, whereas 26% (80/304) and 35% (52/147) experienced ≥3% BWL at the end of cycle 1. Pts with <3% BWL had longer OS than those with ≥3% BWL in both FTD/TPI (median [m] OS: 6.5 vs 4.9 months [mo]; hazard ratio [HR], 0.75; 95% CI, 0.55–1.02) and PBO arms (mOS: 6.0 vs 2.5 mo; HR, 0.32; 95% CI, 0.21–0.49). The PFS HR for pts with <3% BWL vs ≥3% BWL was 0.95 (95% CI, 0.71–1.25; mPFS, 2.1 vs 1.9 mo) in the FTD/TPI group and 0.49 (95% CI, 0.34–0.72; mPFS, 1.9 vs 1.7 mo) in the PBO group. In the pooled ITT population, the unadjusted HR for the <3% vs ≥3% BWL group calculated using a univariate Cox model was 0.58 (95% CI, 0.46–0.73), indicating a strong prognostic effect of early BWL. Results of multivariate analyses were consistent with univariate analyses and suggested that early BWL was both a prognostic ( P<0.0001) and predictive (interaction P=0.0003) factor for OS in pts with mGC/GEJC. Grade ≥3 adverse events (AEs) of any cause were reported in 77% and 82% of FTD/TPI-treated pts in the <3% and ≥3% BWL subgroups, respectively, and in 45% and 67% of placebo-treated pts in the <3% and ≥3% BWL subgroups. Conclusions: To our knowledge, this is the first analysis to show that BWL is negatively associated with survival in pts with mGC/GEJC receiving third- or later-line treatment. In TAGS, early BWL (≥3% BWL at the end of cycle 1) was a strong negative prognostic factor for OS regardless of FTD/TPI or PBO treatment. Grade ≥3 AE frequencies were similar in FTD/TPI-treated pts with <3% or ≥3% BWL. The relationship of BWL to other prognostic factors will be explored further. Clinical trial information: NCT02500043.

Nomogram to estimate the activity of second-line therapy for advanced urothelial carcinoma (UC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4524-4524
Author(s):  
Guru Sonpavde ◽  
Gregory Russell Pond ◽  
Neeraj Agarwal ◽  
Toni K. Choueiri ◽  
Angela Q. Qu ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Phase Ii ◽  
Performance Status ◽  
Phase Iii ◽  
Second Line ◽  
Phase Ii Trials ◽  
Second Line Therapy ◽  
Ecog Performance Status ◽  
Line Therapy ◽  
The Impact

4524 Background: Prognostic factors may impact on endpoints used in phase II trials of second-line therapy for advanced UC. We aimed to study the impact of prognostic factors (liver metastasis [LM], anemia [Hb<10 g/dl], ECOG-performance status [PS] ≥1, time from prior chemotherapy [TFPC]) on PFS6 and RR. Methods: Twelve phase II trials evaluating second-line chemotherapy and/or biologics (n=748) in patients with progressive disease were pooled. PFS was defined as tumor progression or death from any cause. PFS6 was defined from the date of registration and calculated using the Kaplan-Meier method. RR was defined using RECIST 1.0. A nomogram predicting PFS6 was constructed using the RMS package in R (www.r-project.org). Results: Data regarding progression, Hb, LM, PS and TFPC were available from 570 patients. The mean age was 65.1 years, 45.3% had ECOG-PS ≥1, 30.2% had LM, 14.6% had anemia and TFPC was <6 months (mo) in 60.2%. The overall median PFS was 2.7 mo, PFS6 was 22.2% (95% CI: 18.8-25.9) and RR was 17.5% (95% CI: 14.5%-20.9%). For every unit increase in risk group, the hazard of progression increased by 41% and the odds of response decreased by 48% (Table). A nomogram was constructed to predict PFS6 on an individual patient level. Conclusions: PFS6 and RR vary as a function of prognostic factors in patients receiving second-line therapy for advanced UC. A nomogram incorporating prognostic factors might facilitate the evaluation of activity across phase II trials enrolling heterogeneous populations and can help to select and stratify patients for phase III evaluation of suitable agents. [Table: see text]

Improved prognostic classification of patients receiving salvage systemic therapy for advanced urothelial carcinoma.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 311-311 ◽  
Author(s):  
Guru Sonpavde ◽  
Gregory Russell Pond ◽  
Jonathan E. Rosenberg ◽  
Dean F. Bajorin ◽  
Ashley Marie Regazzi ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Urothelial Carcinoma ◽  
Systemic Therapy ◽  
Proportional Hazards ◽  
Performance Status ◽  
Risk Groups ◽  
Cox Proportional Hazards ◽  
Prognostic Impact ◽  
Phase Ii Trials ◽  
Advanced Urothelial Carcinoma

311 Background: Previously identified prognostic factors in patients (pts) receiving salvage systemic therapy for advanced urothelial carcinoma (UC) include performance status (PS), liver metastasis (LM), hemoglobin (Hb) and time from prior chemotherapy (TFPC). Given the prognostic impact of peripheral blood neutrophils (N), lymphocytes (L), thrombocytes (T) and albumin (Alb) in other malignancies, we investigated their impact in the salvage setting of advanced UC. Methods: Phase II trials of salvage systemic therapy were utilized. Data on N, L, T and Alb were required in addition to TFPC, Hb, PS and LM status. N, L, T and Alb were categorized as normal, <lower limit of normal (LLN) and >upper limit of normal (ULN). Cox proportional hazards regression was used to evaluate their association with overall survival (OS). An optimal regression model was constructed using forward stepwise selection and risk groups defined using number of identified adverse risk factors. Trial was a stratification factor. Results: Data was obtained from 10 trials accruing 708 pts. Of these, 682 pts had available TFPC, Hb, PS and LM status, while 631, 554, 649 and 491 had N, L, T and Alb available. Median OS was 6.8 (95% CI: 6.0-7.0) months. Neutrophilia (N>ULN), thrombocytosis (T>ULN) and hypoalbuminemia (Alb <LLN) were significant poor prognostic factors for OS on univariate analyses. After adjustment for TFPC <3 months, Hb <10 g/dl, PS >0 and LM status, only thrombocytosis and hypoalbuminemia remained significant (Table). Risk groups were constructed. Median OS was 8.8, 6.3, 5.0 and 3.8 months for n=290, 220, 123 and 49 patients with 0-1, 2, 3 and ≥4 factors. This 6-factor prognostic model was internally validated with an improvement in the c-index from 0.564 to 0.590. Conclusions: The addition of hypoalbuminemia and thrombocytosis to TFPC, Hb, PS and LM status enhanced the prognostic risk groupings in pts receiving salvage systemic therapy for advanced UC. [Table: see text]

Outcomes for patients ≥75 years with localized gastroesophageal cancer: Experience from the Princess Margaret Cancer Centre.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 189-189
Author(s):  
Akina Natori ◽  
Bryan Chan ◽  
Hao-Wen Sim ◽  
Eric Xueyu Chen ◽  
Geoffrey Liu ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Performance Status ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Cox Proportional Hazards ◽  
Ecog Performance Status ◽  
Free Survival ◽  
Significant Survival ◽  
Comorbidity Index ◽  
Cancer Experience

189 Background: The optimal treatment and outcome for elderly patients (pts) with localized gastroesophageal (GE) cancer remains unclear as they are underrepresented in clinical trials. We aimed to assess survival in pts ≥ 75 years according to treatment received. Methods: A retrospective analysis was performed for all pts aged ≥ 75 years with GE cancer treated in 2012 and 2013. Frailty was measured using the Charlson comorbidity index (CCI) and ECOG performance status (PS). Overall survival (OS) and disease-free survival (DFS) were assessed via uni- and multivariable Cox proportional hazards regression, adjusting for demographics. Logistic regression analyses were used to examine factors impacting treatment choices. Results: Of 70 pts, median age was 82 years (range: 75-98), primary sites were esophageal (40%, with 61% squamous histology), GE junction (24%) and gastric (36%). Baseline characteristics included: PS: 0 (40%), 1 (39%), 2 (14%), 3 (7%); and CCI: 0 (36%), 1 (20%), 2 (21%), ≥ 3 (23%). Treatment received included surgery (33%), radiotherapy (RT) (31%); surgery plus adjuvant chemotherapy (chemo) and/or RT (9%); chemoradiation alone (7%) and 20% had no active treatment. In univariable analysis; age < 85 (p = 0.007) and surgery (p = 0.022) were associated with improved OS. Chemo and RT, either alone or in combination, did not significantly improve OS. In multivariable analysis; age < 85 (HR 0.46, 95% CI: 0.23-0.94, p = 0.034), surgery (HR 0.32, 95% CI: 0.14-0.74, p = 0.008) and CCI < 2 (HR 0.52, 95% CI: 0.27-0.99, p = 0.048) were identified as independent predictors for improved OS. Age ≥ 85 was significantly associated with omission of surgery (OR 3.61, 95% CI: 1.13-14.01, p = 0.041) but in contrast, PS ≥ 2 (p = 0.475) and CCI ≥ 2 (p = 0.939) were not predictive. Conclusions: At our institution, very few pts ≥ 75 years received multimodality therapy for localized GE cancers. Surgery was the only treatment modality associated with a significant survival advantage, and additional chemo and/or RT did not further improve OS. The only predictor for having surgery was age. Consequently, future studies should consider comprehensive assessment for surgery so that eligible elderly pts can benefit.

T-cell–inflamed gene expression profile (GEP) and PD-L1 expression in patients (pts) with esophageal cancer (EC).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 26-26
Author(s):  
Torben Steiniche ◽  
Sun Young Rha ◽  
Hyun Cheol Chung ◽  
Jeanette Bæhr Georgsen ◽  
Morten Ladekarl ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Cells ◽  
Proportional Hazards ◽  
Performance Status ◽  
Stage Iv ◽  
Cox Proportional Hazards ◽  
University Hospital ◽  
Cancer Center ◽  
Ecog Performance Status ◽  
Tissue Samples

26 Background: GEP and PD-L1 expression have been associated with anti–PD-1/PD-L1 therapy. In this retrospective observational study we explored the prognostic value of GEP and PD-L1 expression in pts with EC receiving standard-of-care therapy (SOC). Methods: Tumor tissue samples collected from 2005 to 2017 were procured from Yonsei Cancer Center (South Korea), Memorial Sloan Kettering Cancer Center (USA) and Aarhus University Hospital (Denmark). GEP score was derived from an 18-gene signature using extracted tumor RNA analyzed by NanoString nCounter; GEP high/intermediate (GEP-H/I) and low were defined by a cutoff of –1.540, consistent with pembrolizumab clinical trials. PD-L1 expression was assessed by PD-L1 IHC 22C3 pharmDx assay (Agilent); positive was defined as combined positive score (CPS) ≥ 10, where CPS is the the number of PD-L1–positive cells (tumor cells, lymphocytes and macrophages) divided by the total number of viable tumor cells, multiplied by 100. Associations of GEP score and PD-L1 expression with clinicopathologic variables were analyzed by chi-square test and multiple logistic regression models. Overall survival (OS) from diagnosis date to death date/last follow-up was analyzed using Cox proportional hazards models adjusting for age, sex, stage, region and ECOG performance status (PS). Results: 294 samples with both PD-L1 and GEP data were analyzed. Median age was 65 y (range 33-88); 85% were from men, 58% were stage IV, 63% were esophageal adenocarcinoma (EAC) and 37% were esophageal squamous cell carcinoma (ESCC). Overall 36% of tumors were GEP-H/I: 46% in EAC vs 18% in ESCC. GEP was not associated with OS overall (adjusted hazard ratio [aHR] –0.90; 95% CI 0.68-1.18) or in pts with EAC (aHR 0.93; 95% CI 0.68-1.27) or ESCC (aHR 0.76; 95% CI 0.40-1.44). 21% of tumors were PD-L1-CPS ≥ 10: 18% in EAC and 26% in ESCC. PD-L1 expression was associated with ECOG PS (adjusted odds ratio 0.520; 95% CI 0.309-0.875; P = 0.014) but was not associated with OS overall (aHR 0.89; 95% CI 0.64-1.24) or in pts with EAC (aHR 0.97; 95% CI 0.63-1.49) or ESCC (aHR 1.31; 95% CI 0.73-2.34). Conclusions: Our results suggest that T-cell–inflamed GEP and PD-L1 expression may not be prognostic in pts with EC who received SOC.

scholarly journals Vitamin D Status in Patients With Stage IV Colorectal Cancer: Findings From Intergroup Trial N9741

2011 ◽  
Vol 29 (12) ◽  
pp. 1599-1606 ◽  
Author(s):  
Kimmie Ng ◽  
Daniel J. Sargent ◽  
Richard M. Goldberg ◽  
Jeffrey A. Meyerhardt ◽  
Erin M. Green ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Statistical Power ◽  
Proportional Hazards ◽  
Stage Iv ◽  
Patient Characteristics ◽  
Cox Proportional Hazards ◽  
Stage Iv Colorectal Cancer ◽  
Cox Proportional Hazards Models

Purpose Previous studies have suggested that higher plasma 25-hydroxyvitamin D3 [25(OH)D] levels are associated with decreased colorectal cancer risk and improved survival, but the prevalence of vitamin D deficiency in advanced colorectal cancer and its influence on outcomes are unknown. Patients and Methods We prospectively measured plasma 25(OH)D levels in 515 patients with stage IV colorectal cancer participating in a randomized trial of chemotherapy. Vitamin D deficiency was defined as 25(OH)D lower than 20 ng/mL, insufficiency as 20 to 29 ng/mL, and sufficiency as ≥ 30 ng/mL. We examined the association between baseline 25(OH)D level and selected patient characteristics. Cox proportional hazards models were used to calculate hazard ratios (HR) for death, disease progression, and tumor response, adjusted for prognostic factors. Results Among 515 eligible patients, 50% of the study population was vitamin D deficient, and 82% were vitamin D insufficient. Plasma 25(OH)D levels were lower in black patients compared to white patients and patients of other race (median, 10.7 v 21.1 v 19.3 ng/mL, respectively; P < .001), and females compared to males (median, 18.3 v 21.7 ng/mL, respectively; P = .0005). Baseline plasma 25(OH)D levels were not associated with patient outcome, although given the distribution of plasma levels in this cohort, statistical power for survival analyses were limited. Conclusion Vitamin D deficiency is highly prevalent among patients with stage IV colorectal cancer receiving first-line chemotherapy, particularly in black and female patients.

scholarly journals Clinical Calculator for Early Mortality in Metastatic Colorectal Cancer: An Analysis of Patients From 28 Clinical Trials in the Aide et Recherche en Cancérologie Digestive Database

2017 ◽  
Vol 35 (17) ◽  
pp. 1929-1937 ◽  
Author(s):  
Lindsay A. Renfro ◽  
Richard M. Goldberg ◽  
Axel Grothey ◽  
Alberto Sobrero ◽  
Richard Adams ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Metastatic Colorectal Cancer ◽  
Performance Status ◽  
External Validation ◽  
Cox Proportional Hazards ◽  
Early Mortality ◽  
Phase Iii ◽  
Cancérologie Digestive ◽  
The Impact

Purpose Factors contributing to early mortality after initiation of treatment of metastatic colorectal cancer are poorly understood. Materials and Methods Data from 22,654 patients enrolled in 28 randomized phase III trials contained in the ARCAD (Aide et Recherche en Cancérologie Digestive) database were pooled. Multivariable logistic regression models for 30-, 60-, and 90-day mortality were constructed, including clinically and statistically significant patient and disease factors and interaction terms. A calculator (nomogram) for 90-day mortality was developed and validated internally using bootstrapping methods and externally using a 10% random holdout sample from each trial. The impact of early progression on the likelihood of survival to 90 days was examined with time-dependent Cox proportional hazards models. Results Mortality rates were 1.4% at 30 days, 3.4% at 60 days, and 5.5% at 90 days. Among baseline factors, advanced age, lower body mass index, poorer performance status, increased number of metastatic sites, BRAF mutant status, and several laboratory parameters were associated with increased likelihood of early mortality. A multivariable model for 90-day mortality showed strong internal discrimination (C-index, 0.77) and good calibration across risk groups as well as accurate predictions in the external validation set, both overall and within patient subgroups. Conclusion A validated clinical nomogram has been developed to quantify the risk of early death for individual patients during initial treatment of metastatic colorectal cancer. This tool may be used for patient eligibility assessment or risk stratification in future clinical trials and to identify patients requiring more or less aggressive therapy and additional supportive measures during and after treatment.

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