Association between sites of metastases (mets) and outcomes with immune checkpoint inhibitor (ICI) therapy for advanced urothelial carcinoma (aUC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 445-445
Author(s):  
Dimitrios Makrakis ◽  
Leonidas Nikolaos Diamantopoulos ◽  
Vadim S Koshkin ◽  
Ajjai Shivaram Alva ◽  
Mehmet Asim Bilen ◽  
...  
Keyword(s):  
Cox Regression ◽  
Factor Model ◽  
Poor Response ◽  
Specific Tumor ◽  
Research Sponsor ◽  
Prognostic Implications ◽  
Advanced Urothelial Carcinoma ◽  
Metastatic Sites ◽  
Ecog Ps ◽  
Sites Of Metastases

445 Background: Different metastatic sites have variable prognostic implications in aUC. However, details on response and outcomes with ICI for particular mets is still unknown. We hypothesized that bone and liver mets would have poor response and outcomes with ICIs. Methods: We performed a retrospective cohort study in patients (pts) with aUC who received ICI. We compared overall response rate (ORR) and overall survival (OS) between pts with different mets at ICI initiation. We developed 4 different models: 1) lymph node (LN) only vs other; 2) visceral mets (bone, lung, liver) vs other; 3) bone + liver mets vs bone without liver vs liver without bone vs neither and 4) 6 factor model: a. LN +/- soft tissue/locoregional recurrence b. lung +/- (a) c. bone +/- (b) d. liver +/- (c) e. central nervous system (CNS) +/- (d) and f. other. ORR and OS were compared among groups using multivariable (adjusting for ECOG PS and hemoglobin<10g/dl) logistic regression and cox regression, respectively. Results: We identified 984 pts (24 institutions); 703 and 696 were included in OS and ORR analyses, respectively. Median age at ICI start was 71 (range 32-93), 77% white race, 74% men, 67% ever smokers, 72% pure UC, 18% upper tract UC, 55% extirpative surgery. Prevalence of LN, lung, bone and liver mets at ICI start was 74%, 32%, 27% and 21%, respectively. LN-only mets had significantly higher ORR (44% vs 22%, OR 2.6, p<0.05) and longer mOS (22 vs 8 months, HR 0.5, p<0.05) vs other mets. Visceral mets had significantly lower ORR (21% vs 35%, OR 0.5, p<0.05) and shorter mOS (7 vs 17 months, HR 1.8, p<0.05) vs non-visceral mets. Pts with bone and liver mets had significantly lower ORR and shorter OS vs those with bone or liver mets, which both had significantly lower ORR and shorter OS vs those with neither and with LN +/- local recurrence (Table). Conclusions: In the context of ICI treatment, bone, liver, lung or CNS mets were associated with lower ORR and/or shorter OS, and bone and liver mets were particularly associated with low ORR and short OS. LN-only mets were associated with higher ORR and longer OS. Further work is needed to interrogate site-specific tumor-host immune interactions and identify biomarkers. Research Sponsor: None[Table: see text]

Chromogranine A and neuron-specific enolase as the main predictors of survival for hormone-refractory prostate cancer (HRPC) patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15594-15594
Author(s):  
A. Banu ◽  
E. Banu ◽  
D. Dionysopoulos ◽  
J. Medioni ◽  
F. Scotte ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Regression Analysis ◽  
Gleason Score ◽  
Cox Regression ◽  
Neuron Specific Enolase ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
Metastatic Sites ◽  
Ecog Ps ◽  
The Impact

15594 Background: Clinical studies suggested that the extent of neuro-endocrine differentiation in prostate cancer increases with tumor progression and the development of androgen refractory status. Chromogranine (CgA) and neuron-specific enolase (NSE) are currently explored as surrogate markers. Methods: Eligible chemonaive HRPC patients (pts) were required to have an ECOG performance status (PS) ≤ 2. Before chemotherapy initiation, we quantified NSE, CgA and PSA in the venous blood using commercial kits. We evaluated the impact of baseline NSE, CgA and PSA on overall survival (OS) using multivariate Cox regression analysis, stratified by chemotherapy regimen. Secondary, we studied the correlation between NSE, CgA, PSA and other important variables as age, Gleason score, hemoglobin, number of metastatic sites and ECOG PS. Results: Data of 39 consecutive HRPC pts treated between December 01–06 in a single French center were analyzed. Chemotherapy was docetaxel-based in 92% of pts. Median age was 71 years (range 51–86) and 79% of pts had bone metastases. Elevated NSE, CgA and PSA were observed in 6, 9 and 30% of pts and median levels were 10.8, 67 and 23.3 ng/mL, respectively. Gleason 8–10 was present in 49% of pts. Significant correlations were observed between NSE and the number of metastatic sites and between CgA and age, hemoglobin and ECOG PS. The baseline PSA was only correlated with Gleason score. Median OS for the entire cohort was 24.4 months (95% CI, 18.8–29.9). Two-year OS was 15% and only 19% of patients are dead. Univariate Cox regression analysis showed only a significant relationship between OS and baseline NSE: hazard ratio= 1.09 (95% CI, 1.03–1.16), P=0.006. No other known prognostic factors are related to outcome. A multivariate model including baseline NSE, CgA, ECOG PS and Gleason score showed a 15% rise of the risk of death related to NSE (borderline P value). Conclusions: NSE was the most powerful predictor of survival for HRPC pts. Our results emphasize the theory that cells secreting NSE are chemoresistant, with a negative impact on OS. No significant financial relationships to disclose.

Survival outcomes among older adults (OA) receiving second-line therapy for metastatic CRC (mCRC): 5,289 patients (pts) from the ARCAD Clinical Trials Program.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 7009-7009
Author(s):  
Nadine Jackson McCleary ◽  
William S. Harmsen ◽  
Eric VanCutsem ◽  
Alberto F. Sobrero ◽  
Richard M. Goldberg ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cox Regression ◽  
Survival Outcomes ◽  
Second Line Therapy ◽  
Younger Adults ◽  
Line Therapy ◽  
Treatment Data ◽  
Metastatic Sites ◽  
Ecog Ps ◽  
Trial Participants

7009 Background: Survival outcomes of 2nd line mCRC therapy for OA are poorly understood. We evaluated the rates and survival outcomes of 2nd line therapy among OA age 70+ compared to younger adults (YA) age < 70 following progression on 1st line clinical trials. Methods: Associations between clinical characteristics of pts with available treatment data after progression on 10 of 23 1st line ARCAD trials, time to initial progression (TTiP) and 2nd line therapy were evaluated. Time to progression (TTP) and overall survival (OS) were compared between OA and YA enrolled on 2nd line trials by Cox regression, adjusting for age, sex, ECOG PS, number of metastatic sites, presence of metastasis in lung/liver/peritoneum. Results: Sixteen percent of 1st line ARCAD trial participants were age 70+ (n = 870). Data for 2nd line therapy was available for 60.6% pts (3206/5289). Each additional decade of life was associated with 11% lower odds of receiving 2nd line therapy in multivariate analysis (p = 0.0117). OA participating in 2nd line trials (7.9% age 75+ of 7921) experience similar TTP and OS to YA (mTTP: 5.1 vs. 5.2mos; mOS 11.6 vs 12.4mos, respectively). Conclusions: We did not observe a statistical difference in survival outcomes by age following 2nd line mCRC therapy. Further study is needed to examine unmeasured comorbidity and use of geriatric assessment to select OA likely to benefit from 2nd line therapy. [Table: see text]

Receipt and survival outcomes by age following second-line therapy for metastatic CRC (mCRC): Analysis of 5,289 patients from the ARCAD Clinical Trials Program.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 6-6 ◽  
Author(s):  
Nadine Jackson McCleary ◽  
William S. Harmsen ◽  
Eric VanCutsem ◽  
Alberto F. Sobrero ◽  
Richard M. Goldberg ◽  
...  
Keyword(s):  
Cox Regression ◽  
Subsequent Treatment ◽  
Survival Outcomes ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Treatment Data ◽  
Metastatic Sites ◽  
Ecog Ps ◽  
To Receive

6 Background: Rates and survival outcomes for second-line therapy for mCRC for OA vs. YA are poorly understood. Methods: Pts with available subsequent treatment data after progression from 10 1st line trials were included. Associations between key clinical/disease characteristics, time to initial progression (TTiP) and rate of receipt of second-line therapy were evaluated. Time to progression (TTP) and overall survival (OS) were compared between OA and YA who were enrolled on second-line trials by Cox regression, adjusting for age, sex, ECOG PS, number of metastatic sites, presence of metastasis in lung/liver/peritoneum. Results: OA comprised 16.4% of first-line trials. OA and ECOG PS >0 were less likely to receive second-line therapy than YA. Odds of receiving second-line therapy decreased by 11% for each additional decade of life in multivariate analysis (p=0.0117). OA enrolled in second-line trials experience similar mTTP and mOS as YA (5.1 vs. 5.2mos; 11.6 vs 12.4mos, respectively). Conclusions: OA are less likely to receive 2nd line therapy for mCRC. We did not observe a statistical difference in survival outcomes for OA vs. YA following second-line therapy. Further study is needed to examine unmeasured factors, including comorbidity and functional status given observed inferior outcomes among adults with ECOG PS >0, and consideration given to inclusion of geriatric assessment to select OA likely to benefit from 2nd line therapy for mCRC. [Table: see text]

Prognostic factors for survival in patients with metastatic malign melanoma treated with ipilimumab: Turkish Oncology Group study

2018 ◽  
Vol 25 (7) ◽  
pp. 1658-1664 ◽  
Author(s):  
Yuksel Urun ◽  
H Arzu Yasar ◽  
Hande Turna ◽  
Ece Esin ◽  
A Murat Sedef ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Prognostic Factors ◽  
Cox Regression ◽  
Survival Rates ◽  
Lactic Dehydrogenase ◽  
Rank Test ◽  
Cox Regression Analysis ◽  
Log Rank Test ◽  
Metastatic Sites ◽  
Ecog Ps

Purpose Studies in the last decade show survival improvement with checkpoint blocker therapy in patients with metastatic malign melanoma. Our purpose was to define the efficacy of ipilimumab according to the patient's baseline characteristics including absolute lymphocytes count. Methods We collected the data of 97 patients with advanced malign melanoma treated with ipilimumab (3 mg/kg, q3w) retrospectively. Log-rank test was used to analyze the univariate effects of patient's characteristics (age, gender, metastatic sites, ECOG PS, type of melanoma, lactic dehydrogenase levels, anemia, lymphocytes (L), neutrophils (N), N/L ratio), c-kit and BRAF status. Survival analyses were estimated with Kaplan–Meier method. Cox regression analysis was used to assess the possible factors identified with log-rank test. Results The median age was 58, and 58% were male and 90% of patients had at least one prior systemic therapy. The median survival was 9.7 months for all patients; and the 12- and 24-month survival rates were 43% and 19%, respectively. Absolute lymphocytes count, lactic dehydrogenase level, bone metastasis, the number of metastatic sites, and RECIST response were significantly related to survival. After Cox regression analysis, RECIST response (complete or partial response), absolute lymphocytes count (more than 1500/mm3) and the number of metastatic sites (less than three sites) remained as significant independent prognostic factors for longer survival. Conclusion Ipilimumab improved survival of patients with metastatic malign melanoma. However, patients with fewer metastatic sites and higher absolute lymphocytes count have a significantly better benefit. To determine if these markers could be used to direct patient therapy, further validation analysis is needed.

What is the real impact of bone pain on survival of hormone-refractory prostate cancer (HRPC) patients treated with docetaxel?

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5149-5149 ◽  
Author(s):  
S. Oudard ◽  
E. Banu ◽  
J. Medioni ◽  
D. Dionysopoulos ◽  
O. Cojocarasu ◽  
...  
Keyword(s):  
Bone Pain ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Standard Of Care ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
Hormone Refractory ◽  
The Moment ◽  
Metastatic Sites ◽  
Ecog Ps

5149 Background: Docetaxel is currently the standard of care for HRPC patients (pts). The moment of docetaxel initiation according to the presence or absence of the bone pain was less explored. Methods: Eligible HRPC pts were required to have a baseline bone pain evaluation using the rank-scores as follows: no pain or minimal pain (0), mild (1), moderate and severe pain (2), respectively. The main endpoint was to explore the overall survival (OS) impact of the bone pain (presence and intensity) using the Cox regression analysis, stratified by chemotherapy regimen. OS was calculated between start of chemotherapy and death or last follow-up for censored pts. Secondary endpoint was to evaluate the relationship between PSA doubling time (DT) and survival of pts with minimal or no pain. Results: Data of 145 consecutive HRPC pts treated in a single French center were analyzed. Chemotherapy was docetaxel (67%) or mitoxantrone-based. The median age was 68 years and 93% of pts had bone metastases, 55% with minimal or no pain at baseline. Median OS was 17.3 months (95% CI, 14.6–20) and 93% of pts died. There were OS differences between pain categories ( Table ). Pain intensity was significantly related with OS: hazard ratio=1.50 (95% CI, 1.20–1.88), P=0.0001 at the univariate analysis. Multivariate analysis adjusted by ECOG PS, hemoglobin and number of metastatic sites showed a 16% rise of the risk of death for pts with severe and mild pain. Pts with minimal or no pain at baseline have a different outcome depending of PSA DT (≥ 45 and < 45 days): median OS 32.4 months (95% CI, 16.2–48.7) and 16.5 months (95% CI, 10–22.9), respectively. Conclusions: Our results suggest that HRPC pts with minimal or without bone pain can experience a better OS with docetaxel-based therapy. This motivates the use of docetaxel early, before bone pain apparition. The OS benefit was even higher for asymptomatic pts with a longer PSA DT. [Table: see text] No significant financial relationships to disclose.

First-line PD(L)1 inhibitors for platinum-ineligible advanced urothelial carcinoma (aUC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16024-e16024
Author(s):  
Archana Agarwal ◽  
Gregory Russell Pond ◽  
Ruby Gupta ◽  
Moshe Chaim Ornstein ◽  
Pedro C. Barata ◽  
...  
Keyword(s):  
Cox Regression ◽  
Locally Advanced ◽  
Complete Response ◽  
Cox Regression Analysis ◽  
Best Response ◽  
Advanced Urothelial Carcinoma ◽  
Grade 3 ◽  
Using Data ◽  
Line Setting ◽  
Ecog Ps

e16024 Background: FDA modified the label for 1st-line pembrolizumab or atezolizumab to PD-L1 high cisplatin-ineligible or platinum-ineligible aUC patients (pts) regardless of PD-L1 expression. However, the outcomes when using PD-(L)1 inhibitors for platinum-ineligible pts are unclear. We hypothesized that treatment response and outcomes are comparable to data reported in trials in the 1st line setting of aUC, and conducted a retrospective study to test this hypothesis using data outside the clinical trial setting. Methods: We collected data from 8 institutions for aUC pts with locally advanced unresectable or metastatic UC. The following criteria were used to define pts platinum-ineligible while comorbidities, age and physician discretion were also allowed: Cr Cl < 30 ml/min, ECOG PS 3, Cr Cl 30-59 ml/min and ECOG PS 2. Demographic & clinical variables and outcomes (overall response rate [ORR], overall survival [OS]) were collected. A Cox regression analysis was used to explore associations of baseline variables with response and outcomes. Results: Data were available for 79 pts. Pts received atezolizumab [n = 41], pembrolizumab [n = 28], nivolumab [n = 7] or durvalumab [n = 3]. Median age was 74 years (45-93). Reasons for platinum-ineligibility were: Cr Cl < 30 ml/min (n = 26), ECOG PS 3 (n = 8), ECOG-PS 2 and Cr Cl < 30-59ml/min (n = 14), elderly/co-morbidities (n = 17), and ‘unavailable’ (n = 14). Median OS was 45 weeks (CI 32-80) and ORR was 27.9%: Complete response in 4 pts [5.1%], partial response in 18 pts [22.8%], stable disease in 19 pts [24.1%], progressive disease in 34 pts [43 %]; data for 4 pts [5.1%] was unavailable for best response. Toxicity of any grade and Grade ≥3 was seen in 41.8% and 31.7% of pts, respectively. Hemoglobin (HR = 0.78, 95% CI 0.68 - 0.90, P = 0.001) and liver metastasis (HR = 1.13, 95% CI 0.51 - 2.53, P = 0.036) correlated with OS. Conclusions: The efficacy and toxicities of 1st-line PD-(L)1 inhibitors for platinum-ineligible pts outside clinical trials appear comparable to those reported in trials for unselected cisplatin-ineligible pts. Further validation is required including data based on PD-L1 status and other biomarkers. Platinum-ineligible pts with aUC warrant evaluation of novel safe and effective agents.

First-line PD1/PD-L1 inhibitors for platinum-ineligible advanced urothelial carcinoma (UC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 432-432 ◽  
Author(s):  
Archana Agarwal ◽  
Gregory Russell Pond ◽  
Alexandra Drakaki ◽  
Jae-Lyun Lee ◽  
Mehmet Asim Bilen ◽  
...  
Keyword(s):  
Cox Regression ◽  
Complete Response ◽  
Phase Ii Trials ◽  
First Line ◽  
Cox Regression Analysis ◽  
Prospective Trials ◽  
The Mean ◽  
Advanced Urothelial Carcinoma ◽  
Grade 3 ◽  
Ecog Ps

432 Background: FDA modified the label for the use of 1st-line pembrolizumab or atezolizumab therapy to PD-L1 high cisplatin-ineligible or platinum-ineligible UC patients (pts) regardless of PD-L1 expression. However, the outcomes when using PD1/PD-L1 inhibitors for platinum-ineligible pts are unclear. We conducted a retrospective study to evaluate clinical outcomes with first-line PD1/PD-L1 inhibitors for platinum-ineligible pts with advanced UC in a real-world setting. Methods: We collected data retrospectively from 6 institutions. The following criteria were deemed to render pts platinum-ineligible although physician discretion was also allowed: Cr Cl < 30 ml/min, ECOG-PS 3, Both Cr Cl 30 to < 60 AND ECOG-PS 2. Demographic and clinical variables and outcomes (overall response rate [ORR], overall survival [OS]) were collected. A Cox regression analysis was done to study the association of baseline variables with response and survival. Results: Data were available for 45 pts. Pts received atezolizumab [n = 24], pembrolizumab [n = 11], nivolumab [n = 7] and durvalumab [n = 3]. The mean age was 72.2 (range 45-90) years. The reasons for platinum-ineligibility were: Cr Cl < 30 ml/min (n = 17), ECOG-PS 3 (n = 3), ECOG-PS 2 plus Cr Cl < 60 ml/min (n = 7), elderly with co-morbidities (n = 12), and reason was unavailable for 6 pts. The median OS was 37 weeks (CI 30-80). ORR was 27.3%: Complete response in 3 pts [6.8%], partial response in 9 pts [20.5%], stable disease in 11 pts [25%] and progressive disease in 21 pts [47.7%] and data for 1 patient was unavailable. Toxicity of any grade were seen in 42.2% of pts and Grade ≥3 toxicity in 9 pts’ [20%]. There were no treatment-related deaths. Anemia (HR = 0.75, 95% CI 0.62 - 0.92, P = 0.005) and liver metastasis (HR = 1.17, 95% CI 0.47 - 2.93, P = 0.017) correlated with shorter OS. Conclusions: To our knowledge, this is the 1st report of efficacy and toxicity of PD1/PD-L1 inhibitors as1st-line therapy for platinum ineligible UC. Data appear comparable to those reported previously in unselected cisplatin-ineligible pts receiving pembrolizumab or atezolizumab in phase II trials. Validation is needed in larger datasets and prospective trials.

Sites of metastasis and survival in metastatic renal cell carcinoma (mRCC): Results from the International mRCC Database Consortium (IMDC).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 642-642
Author(s):  
Shaan Dudani ◽  
Guillermo de Velasco ◽  
Connor Wells ◽  
Chun Loo Gan ◽  
Frede Donskov ◽  
...  
Keyword(s):  
Cox Regression ◽  
Underlying Disease ◽  
Patient Counseling ◽  
Metastatic Site ◽  
Disease Biology ◽  
Endocrine Organs ◽  
Metastatic Involvement ◽  
Metastatic Sites ◽  
Genetic Profiles ◽  
Sites Of Metastases

642 Background: Across a variety of malignancies, sites of metastatic involvement are known to be associated with differences in survival. We sought to characterize the frequency and survival of patients with different sites of metastases in mRCC. Methods: Patients with mRCC starting treatment between 2002-2019 were identified and sites of metastatic involvement at time of systemic therapy initiation were documented. The primary outcomes of interest were prevalence of metastatic site involvement and overall survival (OS). Multivariable Cox regression models were performed to adjust for imbalances in IMDC risk factors. Results: A total of 10,320 patients were included. Median age at diagnosis was 60, 73% were male, 87% had clear-cell histology and 80% underwent nephrectomy. The most common sites of metastases were: lung (71%), lymph nodes (49%), bone (36%), liver (21%), adrenal (9%), brain (9%), pancreas (5%), pleura (4%) and thyroid (0.6%). Survival by metastatic site and adjusted hazard ratios are presented in Table. Conclusions: Metastases to endocrine organs (pancreas, thyroid, adrenal) are infrequent but are associated with the longest median OS, whereas bone, liver, pleura and brain metastases are associated with median OS < 18 months. These benchmark values are useful for patient counseling and study design. Sites of metastatic involvement may reflect differences in underlying disease biology, and further work to investigate differences in immune, molecular and genetic profiles between metastatic sites is encouraged.[Table: see text]

Association between prior radical surgery (RS) and outcomes with immune checkpoint inhibitor (ICI) therapy for advanced urothelial carcinoma (aUC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 444-444
Author(s):  
Dimitrios Makrakis ◽  
Daniel Castellano ◽  
Ivan de Kouchkovsky ◽  
Joseph J. Park ◽  
Mehmet Asim Bilen ◽  
...  
Keyword(s):  
Immune Checkpoint Inhibitor ◽  
Overall Response Rate ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Similar Proportion ◽  
Multivariable Model ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Response Table ◽  
Advanced Urothelial Carcinoma

444 Background: It is unclear whether prior RS of primary tumor is associated with response and outcomes with ICI in aUC. We hypothesized that such response and outcomes would not differ based on prior RS. Methods: We performed a retrospective cohort study including patients (pts) with aUC who received ICI. We compared overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) between pts with vs without RS [cystectomy or (nephro)-ureterectomy]. Analysis was stratified based on ICI therapy line (first-line vs salvage). A separate comparison between pts with prior RS or radiation (RT) only or none was also pursued. ORR was compared between groups using logistic regression, as well OS and PFS using cox regression analysis; a multivariable model was built adjusting for calculated Bellmunt score. P<0.05 was significant. Results: We identified 984 pts from 24 institutions; 682, 704 and 673 were included in OS, PFS and ORR analyses, respectively; 54% of pts had prior RS with median age 68 at ICI initiation with RS vs 71 without RS with similar proportion of men (73-74%) and ever smokers (70-71%). The RS group had higher proportion (%) of white pts (77% vs 71%), lower % of pts with Hb<10g/dL at ICI initiation (23% vs 32%) but not significantly higher % of liver metastasis at ICI initiation (23% vs 17%). Bellmunt score with vs without RS was 16% vs 11%, 50% vs 48%, 27% vs 37%, 7% vs 4% for 0, 1, 2, and 3, respectively. ORR and PFS were not significantly different between groups, while prior RS was associated with longer OS (unadjusted HR 0.8, p=0.03). However, after adjustment for Bellmunt score, this association was not significant (table). Upon stratification based on treatment line, OS was longer with prior RS (0.7, p=0.03) for those treated with salvage ICI but this was not significant after adjusting for Bellmunt score. ORR, PFS and OS were not significantly different between pts receiving prior RT only vs RS vs none. Conclusions: Prior RS was not significantly associated with longer OS in pts with aUC receiving ICI after adjusting for Bellmunt score. Further work is needed to interrogate tumor-host immune interactions and identify biomarkers that can be prognostic and/or predictive of ICI response. [Table: see text]

scholarly journals Prognostic implications of alcohol dehydrogenases in hepatocellular carcinoma

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiangye Liu ◽  
Tingting Li ◽  
Delong Kong ◽  
Hongjuan You ◽  
Fanyun Kong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cox Regression ◽  
Expression Profiles ◽  
High Expression ◽  
Rank Test ◽  
Good Survival ◽  
Alcohol Dehydrogenases ◽  
Kaplan Meier ◽  
Incidence And Mortality ◽  
Prognostic Implications

Abstract Background Hepatocellular carcinoma (HCC) is a malignancy with high incidence and mortality rates worldwide. Alcohol dehydrogenases (ADHs) are huge family of dehydrogenase enzymes and associated with the prognosis of various cancers. However, comprehensive analysis of prognostic implications related to ADHs in HCC is still lacking and largely unknown. Methods The expression profiles and corresponding clinical information of HCC were obtained from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test was employed to evaluate the expression of ADHs. Cox regression and Kaplan-Meier analyses were used to investigate the association between clinicopathological characteristics and survival. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses were performed and visualized using R/BiocManager package. Results We found that the expression of ADH1A, ADH1B, ADH1C, ADH4, and ADH6 was significantly downregulated in HCC samples compared to normal liver samples. Our univariate and multivariate Cox regression analyses results showed that high expression of ADH1A, ADH1B, ADH1C, ADH4, and ADH6 was considered as an independent factor with an improved prognosis for the survival of HCC patients. Moreover, our Kaplan-Meier analysis results also revealed that high expression of AHD1A, ADH1B, ADH1C, ADH4, and ADH6 was significantly associated with good survival rate in HCC patients. In addition, GO, KEGG, and GSEA analyses unveiled several oncogenic signaling pathways were negatively associated high expression of ADHs in HCC. Conclusion In the present study, our results provide the potential prognostic biomarkers or molecular targets for the patients with HCC.

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