Prognostic factors (PF) in advanced hepatocellular carcinoma (AHCC): Multivariate analysis and comparison between staging systems (SS) in patients (pts) treated at Memorial Sloan-Kettering Cancer Center (MSKCC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4601-4601 ◽  
Author(s):  
F. D. Huitzil ◽  
M. Capanu ◽  
G. Jacobs ◽  
W. Smith ◽  
E. O’Reilly ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Multivariate Analysis ◽  
Patient Population ◽  
Cox Regression ◽  
Prognostic Index ◽  
Locoregional Therapy ◽  
Rank Test ◽  
Cancer Center ◽  
Advanced Hepatocellular Carcinoma ◽  
Staging Systems

4601 Background: Several SS have been proposed in hepatocellular carcinoma. These include TNM, Okuda, Cancer of the Liver Italian Program (CLIP), Chinese University Prognostic Index (CUPI), and Barcelona Clinic Liver Cancer (BCLC). There is no consensus as to what constitutes the best SS for use by oncologists for pts with AHCC with no locoregional therapy options. We propose to define the PF and compare SS in this patient population. SS may help select pts for systemic therapy, predict outcome, and help in clinical trial design for AHCC. Methods: We retrospectively identified pts with AHCC treated at MSKCC between 2001 and 2006. Clinical, laboratory, tumor characteristics and all four SS were recorded. Survival (S) was measured from the date of development of AHCC to the date of death. S was estimated using Kaplan-Meier’s method, differences in S were tested using the log rank test. A Cox regression model was used for the multivariate analysis. A second Cox regression was done to compare SS and was expressed using the Akaike information (AI) criterion. AI helps determine which SS is the most informative of S. A low AI is favorable. Results: We identified 280 pts. Data on the first 101 pts analyzed are presented. Median age 61 years; 71% males, 29% females; 60% Caucasians, 9% Black, 24% Asians and 5% Hispanics. Etiologies included HCV 24%, HBV 38%, and alcohol 22%. Child Pugh score: A in 65% and B in 29% of pts. Multivariate analysis independent PF for S were albumin (p=0.0358), alkaline phosphatase (ALP) (p=0.001), identified etiology (p=0.008), abdominal pain (p=0.001) and liver tumor extent (more or less than 50% of the liver) (p=0.0043). AI ranked SS as follows: TNM 6th (588.991), TNM 5th (591.373), BCLC (541.095), Okuda (540.490), CLIP (537.8), and CUPI (526.483). CUPI S was 19.47 months (m) for low, 5.89 m for medium, and 1.36 m for high risk pts. Conclusions: Pts with AHCC who are treated by oncologists in this US-based population have distinct PF. CUPI provided the best prognostic information for our patient population. CUPI may be suggested as the SS to use clinically for AHCC. These results need prospective validation. No significant financial relationships to disclose.

scholarly journals Advanced Hepatocellular Carcinoma: Which Staging Systems Best Predict Prognosis?

2010 ◽  
Vol 28 (17) ◽  
pp. 2889-2895 ◽  
Author(s):  
Fidel-David Huitzil-Melendez ◽  
Marinela Capanu ◽  
Eileen M. O'Reilly ◽  
Austin Duffy ◽  
Bolorsukh Gansukh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Performance Status ◽  
Prognostic Index ◽  
Discrimination Performance ◽  
Cancer Center ◽  
Advanced Hepatocellular Carcinoma ◽  
Carcinome Hépatocellulaire ◽  
Advanced Hcc ◽  
Sixth Edition ◽  
Staging Systems

Purpose The purpose of cancer staging systems is to accurately predict patient prognosis. The outcome of advanced hepatocellular carcinoma (HCC) depends on both the cancer stage and the extent of liver dysfunction. Many staging systems that include both aspects have been developed. It remains unknown, however, which of these systems is optimal for predicting patient survival. Patients and Methods Patients with advanced HCC treated over a 5-year period at Memorial Sloan-Kettering Cancer Center were identified from an electronic medical record database. Patients with sufficient data for utilization in all staging systems were included. TNM sixth edition, Okuda, Barcelona Clinic Liver Cancer (BCLC), Cancer of the Liver Italian Program (CLIP), Chinese University Prognostic Index (CUPI), Japan Integrated Staging (JIS), and Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire (GETCH) systems were ranked on the basis of their accuracy at predicting survival by using concordance index (c-index). Other independent prognostic variables were also identified. Results Overall, 187 eligible patients were identified and were staged by using the seven staging systems. CLIP, CUPI, and GETCH were the three top-ranking staging systems. BCLC and TNM sixth edition lacked any meaningful prognostic discrimination. Performance status, AST, abdominal pain, and esophageal varices improved the discriminatory ability of CLIP. Conclusion In our selected patient population, CLIP, CUPI, and GETCH were the most informative staging systems in predicting survival in patients with advanced HCC. Prospective validation is required to determine if they can be accurately used to stratify patients in clinical trials and to direct the appropriate need for systemic therapy versus best supportive care. BCLC and TNM sixth edition were not helpful in predicting survival outcome, and their use is not supported by our data.

IV-HCC: Clinical and prognostic implications of plasma IGF-1 and VEGF in patients with hepatocellular carcinoma.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 155-155
Author(s):  
A. O. Kaseb ◽  
J. Morris ◽  
M. Hassan ◽  
E. Lin ◽  
L. Xiao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Growth Factor ◽  
Cox Regression ◽  
Rank Test ◽  
Cancer Center ◽  
P Value ◽  
Poor Overall Survival ◽  
Cut Point ◽  
Staging Systems

155 Background: Hepatocellular carcinoma (HCC) is a vascular tumor, derived mainly by vascular endothelial growth factor (VEGF)-mediated angiogenesis. It is always associated with chronic liver disease (CLD) and cirrhosis, which directly affect survival of HCC patients. Insulin-like growth factor-1 (IGF-1) is produced predominantly in the liver, and therefore, CLD is associated with low levels of IGF-1. Methods: 288 new consecutive patients with HCC were eligible for the study between 2001 and 2008 at M. D. Anderson Cancer Center. Baseline clinicopathologic features, CLIP and BCLC staging, plasma IGF-1 and VEGF levels were available and multivariate Cox regression models and median survival were calculated. Kaplan-Meier curves were used to estimate overall survival and the log-rank test was used to compare survival probabilities in patients with different IGF-1 and VEGF levels. Recursive partitioning was used to determine the optimal cut point for IGF-1 and VEGF, using repeated training/validation samples, each using 2/3 of the data to determine the best cut point and the remaining 1/3 to validate it. Prognostic ability of different molecular staging systems was compared using C-index. Results: Lower plasma IGF-1 and higher plasma VEGF levels significantly correlated with advanced clinicopathologic parameters and poor overall survival, with an optimal cut point of 26 pg/mL and 450 pg/mL respectively. The combination of low IGF-1 and high VEGF predicts median OS of 2.7 months compared with 19 month for patients with high IGF-1 and low VEGF (p-value=<0.0001), and further refines the prognostic ability of BCLC and CLIP HCC staging systems (p<0.0001). Conclusions: Molecular classification of HCC using baseline plasma IGF-1 and VEGF significantly correlated with clinical features and survival of HCC patients. Furthermore, integrating IGF-1 and VEGF into HCC staging systems, CLIP and BCLC, significantly enhanced their ability to predict prognosis. It may prove to be useful in designing strategies to personalize treatment approaches to these patients. No significant financial relationships to disclose.

HER2-low and gastric cancer: A prognostic biomarker?

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16086-e16086
Author(s):  
Bruno Cezar de Mendonça Uchôa ◽  
Rafaela Pirolli ◽  
Luciana Beatriz Mendes Gomes Siqueira ◽  
Francisca Giselle Rocha Moura ◽  
Ana Paula Rondina Correa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Multivariate Analysis ◽  
Prognostic Value ◽  
Cox Regression ◽  
Prognostic Biomarker ◽  
Statistical Significance ◽  
Gastroesophageal Junction ◽  
Rank Test ◽  
Cancer Center ◽  
First Line

e16086 Background: The role of HER2 positive (HER2+) as a prognostic biomarker for gastric/gastroesophageal junction cancer (G-GEJC) is controversial. Recently, the HER2-low (HER2l) concept has emerged and proved to predict response to trastuzumab deruxtecan in metastatic scenario. Data on HER2l prognostic value are missing. Methods: All consecutive patients with metastatic G-GEJC, tested for HER2 in the primary tumor or in the metastatic tissue before initiating first-line therapy at A.C. Camargo Cancer Center, were retrospectively recruited. The primary objective was to compare the overall survival (OS: from the metastasis diagnosis to death by any cause) between HER2l and HER2 negative (HER2-) populations. Secondarily, we aimed to compare the first-line progression-free survival (PFS) between HER2l and HER2-, to analyze prognostic factors associated with OS and to compare the OS between HER2+ and HER2l/HER2-. The HER2 immunohistochemistry (IHC) tests were performed with the Ventana anti-HER2/neu kit, by specialized gastrointestinal pathologists of the study center, using the AJCC HER2 scoring criteria for gastric cancer. In situ hybridization (ISH) was done when IHC 2+ was detected. HER2+ were IHC 3+ or 2+ amplified by ISH; HER2l, 1+ or 2+ non-amplified; HER-, 0+. Kaplan-Meier curves, Log-Rank test and Cox regression were used for survival analysis. Cox regression was used for uni and multivariate analysis. Results: From June, 2008 to July, 2020, 398 patients were included (48 HER2+; 103 HER2l; 247 HER2-). The median follow-up was 31 months (m). Median age at diagnosis was 58 years; the majority were men (62.8%), caucasian (50.8%), with gastric (81% vs 19% GEJ), diffuse (50.3%), de novo metastatic (57.0%) tumors. In comparison to HER2l/HER2-, HER2+ group had superior rates of men, GEJC, intestinal subtype and non-visceral metastasis. Central nervous system metastases were uncommon, and proportionally higher in HER2+ tumors (HER2+: 6.2%; HER2l: 2.9%; HER2-: 2.0%; p = 0.27). There were no imbalances between HER2l and HER2- groups. The median OS was similar for HER2l and HER2- (13m for both; HR 1.0, 95%CI 0.76-1.31; p = 1.0), as it was the PFS (5m for both; HR 0.84, 95%CI 0.65-1.08; p = 0.18). These results did not vary on dependence of IHC + (0 vs 1 + vs 2+). HER2+ tumors had a superior median OS (17m vs 13m for HER2l/HER2-; HR 0.70, 95%CI 0.49-0.99; p = 0.046). When ungrouping HER2l/HER2-, this numerical difference remains, with a loss of statistical significance (17m vs 13m vs 13m; HR 0.87, 95%CI 0.74-1.02; p = 0.12). HER2+, > 1 line of treatment and metastasectomy were predictive for improved OS in multivariate analysis. HER2l was neither predictive for OS nor PFS. Conclusions: Although HER2-low emerged as a new predictive biomarker in metastatic gastric cancer, its prognostic value could not be proved in this study, with an absence of impact in OS. HER2+, however, was associated with improved survival.

Staging of advanced hepatocellular carcinoma patients in the targeted therapy era.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 209-209
Author(s):  
Neeraj Nailesh Shah ◽  
Manal Hassan ◽  
Lianchun Xiao ◽  
James L. Abbruzzese ◽  
Jeffrey Morris ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Targeted Therapy ◽  
Prognostic Index ◽  
Predictive Ability ◽  
Staging System ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Sorafenib Group ◽  
Staging Systems

209 Background: Several hepatocellular carcinoma (HCC) staging systems are currently available. However, they were all developed before the targeted therapy era prevailed in the last decade which has changed the natural history of the disease. Our study goal was to test the performance of different HCC staging systems in patients with HCC who were treated at our institution during the last decade. Methods: We prospectively enrolled 438 patients from early 2000 to late 2009. Baseline clinicopathologic parameters and staging were available, including the TNM, Cancer of the Liver Italian Program (CLIP), Barcelona Clinic Liver Cancer (BCLC), Okuda, and Chinese University Prognostic Index (CUPI). We performed survival and cox-regression analyses, and compared the staging systems’ predictive ability using Harrell's C-index. Finally, we performed a subgroup analysis of 3 independent cohorts based on whether or not they received sorafenib, whether or not they had hepatitis, and whether or not they had cirrhosis. Results: The overall survival was 13.9 months. Overall, CLIP score was the most predictive staging system with a C-index of 0.71. 187 patients were treated with targeted therapies and 138 were treated with sorafenib after it was approved in 2007. CLIP score was the most predictive staging system with a C-index of 0.71 in the no sorafenib group, and 0.74 in the sorafenib group. In hepatitis patients, CLIP topped amongst all staging systems with a C-index of 0.75, and in patients without hepatitis, despite all staging systems having a poor predictive ability, CLIP score still had the highest C-index of 0.67. Similarly, CLIP score had the best predictive ability in patients with and without pre-existing liver cirrhosis, with C-indices of 0.73 and 0.68 respectively. There was no statistically significant interaction between CLIP score and hepatitis status, and CLIP score and liver cirrhosis. Thus, overall the CLIP score was the best predictive system in all cohorts. Conclusions: Our results suggest that the CLIP score has the highest stratification ability in our advanced HCC patient population, including several subgroups. Our study confirms the utility of the CLIP score to stratify advanced HCC patients in clinical trials.

A large multicenter study evaluating prognosis and chemosensitivity of metastatic colorectal cancers with microsatellite instability.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3536-3536 ◽  
Author(s):  
David Tougeron ◽  
Benjamin Sueur ◽  
David Sefrioui ◽  
Lucie Gentilhomme ◽  
Thierry Lecomte ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Objective Response ◽  
Prospective Trial ◽  
Prognostic Index ◽  
Rank Test ◽  
Colorectal Cancers ◽  
First Line ◽  
Peritoneal Carcinosis

3536 Background: Deficient Mismatch Repair (dMMR) in colorectal cancers (CRC) represent 12% of all tumors. In non-metastatic CRC setting, dMMR are associated with good prognosis but also with resistance to adjuvant 5-FU chemotherapy. In metastatic CRC (mCRC) setting, dMMR is found in less than 5% and its influence on prognosis and treatment response is little known. Methods: This multicenter retrospective study included all consecutive patients with dMMR mCRC treated between 2005 and 2015 in 17 centers. The Kaplan-Meier method was used to calculate overall survival (OS) and progression-free survival (PFS). Prognostic variables were evaluated in univariate analysis using the Log rank test and in multivariate analysis using the Cox regression model. Results: A total of 198 patients with dMMR mCRC were included (median age 64.6 years). dMMR mCRC were mostly diagnosed with synchronous metastases (59%) and frequent peritoneal carcinosis (43%). Lynch syndrome was found in 34% of cases and 36% of tumors had a BRAFV600E mutation. Median OS was 20.6 months. A low risk Kohne's prognostic index (HR = 0.40 [0.22-0.72], p = 0.02) and absence of peritoneal carcinosis (HR = 0.51 [0.29-0.90], p = 0.02) were associated with better OS in multivariate analysis. Main first-line regimens were 5FU-based (n = 20), oxaliplatin-based (n = 75) or irinotecan-based (n = 46) chemotherapy. Median PFS on first-line treatment was 5.9 months. The objective response rate (ORR) was 0%, 19% and 36% for 5FU-based, oxaliplatin-based and irinotecan-based chemotherapies, respectively (p = 0.02). A trend for a longer PFS (3.3, 5.5 and 10.2 months, respectively, p = 0.06) and OS (17.7, 21.1 and 34.2 months, respectively, p = 0.05) was also observed for irinotecan-based chemotherapy. The addition of bevacizumab to chemotherapy was associated with a significant increase of ORR (p = 0.01) and PFS (p = 0.04) as compared to the addition of an anti-EGFR therapy. Conclusions: This study suggests that dMMR mCRC are associated with poor prognosis and chemoresistance, especially to 5FU-based chemotherapy. Efficacy of irinotecan and bevacizumab should be evaluated in a prospective trial in combination with immune checkpoint inhibitors.

Anti-GD2 immunotherapy in adults with high-risk neuroblastoma (HR-NB): The Memorial Sloan Kettering Cancer Center (MSKCC) experience.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10550-10550 ◽  
Author(s):  
Maya Suzuki ◽  
Brian H. Kushner ◽  
Kim Kramer ◽  
Ellen M. Basu ◽  
Stephen S. Roberts ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Rank Test ◽  
Cancer Center ◽  
Mycn Amplification ◽  
Cell Transplant ◽  
Adult Onset ◽  
Term Survival ◽  
Stage 4

10550 Background: The diagnosis of NB in adulthood is rare and little is known about its biology and clinical course. There is no established therapy for adult NB. Anti-GD2 immunotherapy is now standard in children with HR-NB but its use has not been reported in adults. Methods: After obtaining IRB waiver, records of all patients with adult-onset (≥18 years) NB seen at MSKCC between 1983 and 2015 were reviewed. Overall survival (OS) was tested by log-rank test. Cox-regression was used for multivariate analysis. Results: The subjects were 42 adults (median: 25; range18-71 years); 23 male and 19 female. Five, 1, 1 and 35 patients had INSS stage 1, 2, 3 and 4 disease, respectively. Genetic abnormalities included somatic ATRX (59%) and ALK mutations (43%) but not MYCN-amplification. 16 patients remain alive at a median follow-up of 5.3 years. OS for non-stage 4 patients was superior to stage 4 (median survival 14.6 vs 5.3 years; p < 0.05). However 5/7 patients with < stage 4 NB progressed to stage 4. Among 35 stage 4 patients, 4 achieved complete remission (CR) after induction chemotherapy and surgery, 11 underwent autologous stem cell transplant (ASCT) and 15 received multiple cycles of anti-GD2 antibodies 3F8 or hu3F8 without complications. In univariate analysis, patients ≤ 29 years old (n = 24) at diagnosis, those achieving CR, and those receiving anti-GD2 antibodies had superior OS (p < 0.05 for each). ASCT was not beneficial (p = 0.3 for ASCT vs no ASCT). For stage 4 patients, anti-GD2 immunotherapy was associated with favorable OS in multivariate analysis (95% CI of anti-GD2 antibody: 1.270 to 7.990). Conclusions: Adult-onset stage 4 NB demonstrates a high incidence of somatic mutations and is only partially chemosensitive. However, 3F8/hu3F8-based anti-GD2 immunotherapy appears to improve long-term survival and is well tolerated.

scholarly journals 452 Preliminary analysis of a real-world study (RWS) of camrelizumab treatment in primary liver cancer (PLC)

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A479-A480
Author(s):  
Zhendong Chen ◽  
Nianfei Wang ◽  
Dayong Luo ◽  
Bo Jiang ◽  
Mu Yuan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Group Performance ◽  
Primary Liver Cancer ◽  
Locoregional Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
Open Label ◽  
Patient Disposition ◽  
Ecog Ps

BackgroundImmune checkpoint inhibitors (ICIs) have revolutionized the landscape of PLC management at all evolutionary stages.1 As an anti-programmed cell death-1 (PD-1) antibody, camrelizumab monotherapy and in combination with apatinib, an anti-angiogenetic tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR)-2, chemotherapy or locoregional therapy, have demonstrated their efficacy in advanced hepatocellular carcinoma (HCC).2 3 4 5MethodsThis prospective, open-label, multi-center, observational RWS was conducted to evaluate efficacy and safety of camrelizumab in treatment of PLC in clinical practice. Eligible patients were histopathologically or cytologically identified HCC or intrahepatic cholangiocarcinoma, who were going to receive camrelizumab treatment, with age ≥18 ages, Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0–2 and Child-Pugh score ≤ 9. Patients were treated at clinician discretion. Three hundred patients were planned to enroll, including advanced or peri-operative PLC. The primary endpoint was progress-free survival for advanced PLC, whose efficacy was available to analysis. Efficacy was assessed per Response Evaluation Criteria in Solid Tumors version 1.1.ResultsFrom March 29, 2020 to June 10, 2021,a total of 147 eligible patients of advanced PLC were enrolled and included in this interim analysis, with 128 (87.1%) men, 130 (94.9%) ECOG PS of 0–1, 139 (94.6%) HCC, 74 (50.4%) Barcelona Clinic Liver Cancer stage C, 98 (66.7%) Child-Pugh B, and 72 (49.0%) with extrahepatic metastases, shown in table 1. Of the 147 patients, 45 (30.1%) patients were treated with camrelizumab monotherapy, 79 (53.8%) patients with combination with angiogenesis inhibitors, of which 55 (37.4%) in combination with apatinib, 21 (14.3%) patients with camrelizumab and chemotherapy. Patients, who had at least one efficacy assessment, were included in the efficacy analyses. Up to July 19, 2021, with a median follow time of 6.2 months, 132 patients were available for efficacy analyses. Patient disposition was shown in figure 1. Objective response rate (ORR) and disease control rate (DCR) were 10%/30.8%/35.3% and 75.0%/86.5%/70.6% in camrelizumab monotherapy/combined with apatinib/combined with chemotherapy, respectively. (table 2) The most common camrelizumab-treatment related adverse events (AEs) included reactive cutaneous capillary endothelial proliferation (RCCEP) (12, 8.2%), ICI-induced pneumonia (2, 1.4%), enterocolitis (2, 1.4%), and nephritis (1, 0.7%), of which all these AEs recovered. Other AEs included increase of transaminase (5, 3.4%) and hypertension (4, 2.7%). All AEs were 1–2 grade and no treatment-related death occurred.Abstract 452 Table 1Baseline characteristicsAbstract 452 Figure 1Patient dispositionAbstract 452 Table 2Confirmed tumor response assessed by investigators per RECIST v1.1ConclusionsCamrelizumab, combined with anti-angiogenetic agents or chemotherapy, or monotherapy, demonstrated good efficacy and safety in treatment of PLC.Trial RegistrationChiCTR2000034264ReferencesLlovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nat Rev Dis Primers 2021;7(1):6–28.Qin S, Ren Z, Meng Z, et al. Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, randomised, phase 2 trial. Lancet Oncol 2020;21(4):571–580.Xu J, Shen J, Gu S, et al. Camrelizumab in Combination with Apatinib in Patients with Advanced Hepatocellular Carcinoma (RESCUE): A Nonrandomized, Open-label, Phase II Trial. Clin Cancer Res 2021;27(4):1003–1011.Mei K, Qin S, Chen Z, et al. Camrelizumab in combination with apatinib in second-line or above therapy for advanced primary liver cancer: cohort A report in a multicenter phase Ib/II trial. J Immunother Cancer 2021;9(3).Qin S, Bai Y, Lim HY, et al. Randomized, multicenter, open-label study of oxaliplatin plus fluorouracil/leucovorin versus doxorubicin as palliative chemotherapy in patients with advanced hepatocellular carcinoma from Asia. J Clin Oncol 2013;31(28):3501–3508.Ethics ApprovalThis study was approved by China registered clinical trial ethics review committee with No.ChiECRCT20200042.

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