Natural history of T1N0M0 hepatocellular carcinoma: Large scale study in the United States.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 416-416
Author(s):  
Humaid Obaid Al-Shamsi ◽  
Reham Abdel-Wahab ◽  
Manal Hassan ◽  
Gehan Botrus ◽  
Ahmed S Shalaby ◽  
...  

416 Background: Prognostic modeling of hepatocellular carcinoma (HCC) is complex due to preexisting cirrhosis in most cases. Tumor features and factors related to functional hepatic reserve must be taken into account when considering treatment options or counseling patients about their survival. The key prognostic factors may vary at different stages of the disease especially for early stage. Methods: From 1992 to 2011 total of 397 HCC patients with T1N0M0 were referred to MD Anderson Cancer Center for treatment. Detailed clinical-pathologic information were retrieved from medical records. Univariate analysis was done using the c2or Fisher’s exact test for categorical variables. Kaplan-Meier used to estimate the median overall survival (OS). Multivariate cox regression analysis was performed to estimate the hazard ratio (HR) and 95% confidence interval (CI). Results: The male to female ratio was3:1. The mean age ± standard deviation was 65.04 ± 12.5, 57.2% were non-viral related, 59.7% had cirrhosis, and 9.3% had poorly differentiated tumor (PDT). Median OS (95% CI) was 28.5 months (23.6 – 33.4). First line therapy is summarized in table 1. Surgical intervention was similar to systemic therapy with 76% reduction in mortality compared to non-treated group. Restricted analysis among cirrhotic patients showed similar results. PDT was associated with significant poor prognosis compared to well-differentiated tumor, HR (95% CI) was 2.42 (1.36-4.28) after adjustment for demographic, epidemiological, and clinical factors. Conclusions: Our results indicate that T1N0M0 HCC patients have similar outcome with systemic therapy and surgery which could be beneficial for patients with underlying cirrhosis and high risk of postsurgical complications. [Table: see text]

2021 ◽  
Author(s):  
Rui Feng ◽  
Jian Li ◽  
Weiling Xuan ◽  
Hanbo Liu ◽  
Dexin Cheng ◽  
...  

Abstract Background Hepatocellular carcinoma (HCC) is a prevalent primary liver cancer and the main cause of cancer mortality. Its high complexity and dismal prognosis bring dramatic difficulty to treatment. Due to the disclosed dual functions of autophagy in cancer development, understanding autophagy-related genes devotes into seeking novel biomarkers for HCC. Methods Differential expression of genes in normal and tumor groups was analyzed to acquire autophagy-related genes in HCC. GO and KEGG pathway analyses were conducted on these genes. Genes were then screened by univariate regression analysis. The screened genes were subjected to multivariate Cox regression analysis to build a prognostic model. The model was validated by ICGC validation set. Results Altogether, 42 autophagy-related differential genes were screened by differential expression analysis. Enrichment analysis showed that they were mainly enriched in pathways including regulation of autophagy and cell apoptosis. Genes were screened by univariate analysis and multivariate Cox regression analysis to build a prognostic model. The model was constituted by 6 feature genes: EIF2S1, BIRC5, SQSTM1, ATG7, HDAC1, FKBP1A. Validation confirmed the accuracy and independence of this model in predicting HCC patient’s prognosis. Conclusion A total of 6 feature genes were identified to build a prognostic risk model. This model is conducive to investigating interplay between autophagy-related genes and HCC prognosis.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 289-289 ◽  
Author(s):  
Reham Abdel-Wahab ◽  
Manal Hassan ◽  
Robert A. Wolff ◽  
Sahin Lacin ◽  
Humaid Obaid Al-Shamsi ◽  
...  

289 Background: Alpha-1 Antitrypsin (A1AT) is a circulating liver derived protease inhibitor. There is an evolving evidence that elevated level of A1AT stimulate tumor cell proliferation, and invasion in different cancers. Despite A1AT well-known involvement in hepatic fibrosis, its role in hepatocellular carcinoma (HCC) pathogenesis is not well characterized. The current study aimed to investigate the association between A1AT and clinicopathologic features and prognosis of patients with HCC. Methods: Between 2001 and 2014, total of 766 HCC patients from MD Anderson Cancer Center were enrolled. Under IRB approval, baseline patients’ clinical characteristics were retrieved from medical records. The normal level of plasma A1AT was defined based on the Mayo clinic reference value (1 – 1.9 mg/ml). Survival analysis included Kaplan Meier statistic and Cox regression analysis. Multivariate Hazard Ratio (HR) and 95% Confidence interval (CI) were estimated to determine the independent effect of A1AT on HCC prognosis. Results: The mean and standard deviation of plasma A1AT level was 2.7 ± 0.98 mg/mL. All patients were categorized into 2 groups: group 1 (N = 156) with normal serum level ( ≤ 1.9) and group 2 (N = 610) with higher values ( > 1.9). Median survival (months), 95% CI were 24.4 (18.02 – 30.7) and 11.6 (9.6 – 13.6) in group 1 and 2 respectively, (P < .0001). Patients in group 2 experienced poor clinical characteristics than group 1. The estimated multivariate HR (95% CI) for A1AT is 1.4 (1.1 – 1.7) after adjustment for age, sex, race, cirrhosis, AFP, TNM staging, and treatment exposure. Conclusions: High plasma level of A1AT is associated with higher α-feto protein, advanced TNM and Barcelona clinic liver cancer (BCLC) staging and poor survival of HCC patients. Recent preliminary studies suggested that changes in glycosylaion of production of A1AT by HCC cells correlates with the microenvironment inflammatory and proteolytic activities, which are probably linked to advanced clinicopathologic features and poorer survival. Future excremental studies are warranted to understand the mechanistic pathways of potential A1AT involvement in HCC initiation and progression.


2011 ◽  
Vol 26 (2) ◽  
pp. 108-116 ◽  
Author(s):  
Li Chen ◽  
Yan Shi ◽  
Cheng-ying Jiang ◽  
Li-xin Wei ◽  
Ya-li Lv ◽  
...  

Aims To evaluate the prognostic value of vascular endothelial growth factor (VEGF), platelet-derived growth factor receptor-alpha (PDGFR-α) and beta (PDGFR-β) expression in patients with hepatocellular carcinoma (HCC). Methods The expression of PDGFR-α, PDGFR-β and VEGF in 63 HCC patients who underwent curative resection was examined by immunohistochemistry (IHC). The correlations between the expression of these biomarkers and the clinicopathological characteristics were analyzed. Patient survival was analyzed by univariate analysis and Cox proportional hazards model. Results Univariate survival analysis showed that PDGFR-α or PDGFR-β overexpression was of no prognostic significance in predicting disease-free survival (DFS) and overall survival (OS) (p>0.05), while VEGF overexpression and PDGFR-α/PDGFR-β/VEGF coexpression were significantly correlated with worse DFS and poorer OS in HCC patients (P<0.05). More importantly, PDGFR-α/PDGFR-β/VEGF coexpression was an independent prognostic marker for poor survival as indicated by multivariate Cox regression analysis (DFS, hazard ratio 3.122, p=0.001; OS, hazard ratio 4.260, p=0.000). Conclusions Coexpression of PDGFR-α, PDGFR-β and VEGF could be considered an independent prognostic biomarker for predicting DFS and OS in HCC patients. This result could be used to identify patients at a higher risk of tumor recurrence and poor prognosis, and help to select therapeutic schemes for the treatment of HCC.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 562-562
Author(s):  
Mohamedtaki Abdulaziz Tejani ◽  
Anna ter Veer ◽  
Dana Milne ◽  
Rebecca Ottsesen ◽  
Tanios S. Bekaii-Saab ◽  
...  

562 Background: Appendiceal neoplasms are rare and represent 1% of intestinal tumors in the United States. The role and efficacy of modern systemic therapy in advanced appendiceal adenocarcinoma has not been established. Methods: Patients with recurrent or metastatic appendiceal adenocarcinoma in the NCCN Colorectal Database (2005-2010) were analyzed. Study objectives were to describe and evaluate the efficacy of systemic therapy and investigate relationships with clinicopathologic features. Cox regression analysis was performed to identify predictors of PFS and OS. The hazard ratio and 95% CI from Cox models and median PFS and OS from Kaplan-Meier curves were reported. Results: Of 177 patients with advanced appendiceal carcinoma, 81 (46%) received systemic therapy for measurable disease and are the focus of this report (patients undergoing IP chemotherapy excluded). Patient/tumor characteristics: median age 50 (range 20-82), ECOG PS 0/1 (67%/22%), mucinous/non-mucinous (44 %/ 51%), 91% peritoneal and 15% liver metastases. 70% of patients had primary surgical debulking. Common chemotherapy regimens included FOLFOX with or without bevacizumab (n=30 and n=28), FOLFIRI (n=11), and single-agent fluoropyrimidine (n=7). Among 70 patients with a recorded best response, the response rate (RR) was 46% with 31% stable disease. Median PFS was 1.0 year (95% CI: 0.7-1.9) and OS was 2.1 years (95% CI: 1.7-2.6). Patients with non-mucinous histology, high grade tumors and non-debulking surgery had worse PFS and OS (Table). Conclusions: Treatment of advanced appendiceal adenocarcinoma at NCCN centers commonly incorporates agents utilized for colorectal cancer. RR, PFS and OS are comparable to those achieved in the treatment of metastatic CRC and support routine use of these regimens in clinical practice. Poor prognostic factors include non-mucinous histology, high grade and not undergoing debulking surgery. [Table: see text]


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3051-3051 ◽  
Author(s):  
Yukiya Narita ◽  
Keiji Sugiyama ◽  
Seiichiro Mitani ◽  
Kazunori Honda ◽  
Toshiki Masuishi ◽  
...  

3051 Background: Anti-PD-1 monotherapy has proven effective for the patients (pts) with MGC. However, the identification of biomarkers for predicting clinical outcomes remain as critical needs. We aimed to identify baseline characteristics associated with time to treatment failure (TTF) or overall survival (OS) for anti-PD-1/PD-L1 monotherapy as second- or later-line therapy in MGC. Methods: Routine blood count parameters and clinical characteristics at baseline were retrospectively investigated in 31 pts with MGC in Aichi Cancer Center Hospital. Endpoints were TTF and OS following anti-PD-1/PD-L1 monotherapy. Kaplan-Meiyer and Cox regression analysis were applied for survival analyses. Results: Patient characteristics were as follows: median age (range), 68 (47–83); ECOG performance status (PS) 0/1, 21/10; PM +ve/-ve, 12/19; No. of metastatic sites 1–2/≥3, 18/13; No. of prior chemotherapy regimens 1–2/≥3, 11/20; and absolute eosinophil count (AEC) <150/≥150 /μl, 14/17. Objective response rate and disease control rate (RECIST ver. 1.1) were 26% vs. 0% (odds ratio [OR], 3.76; P = 0.12) and 79% vs. 50% (OR, 3.58; P = 0.12) in the PM -ve group (Cohort A) and the PM +ve group (Cohort B), respectively. On univariate analysis, the pts with poor PS, PM +ve, and high AEC were significantly poor TTF; and poor PS and PM +ve were significantly identified as prognostic factors of poor OS. On multivariate analysis, only PM +ve was independent negative impact not only for TTF but also for OS. Median TTF and OS were 5.4 vs. 1.3 months (M) (adjusted hazard ratio [HR], 4.29; 95%CI, 1.60–11.5; P < 0.01) and 28.2 vs. 7.5 M (adjusted HR, 3.68; 95%CI, 1.25–10.8; P = 0.02) in Cohort A and Cohort B. Six-months TTF probabilities of 42% vs. 0% ( P = 0.03) and one-year OS probabilities of 58% vs. 8% ( P< 0.01) were observed in Cohort A compared to in Cohort B. Conclusions: PM -ve in the pts treated with anti-PD-1/PD-L1 monotherapy was associated with better efficacy. In the pts with PM -ve, anti-PD-1/PD-L1 monotherapy could be adapted in first-line therapy. [Table: see text]


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15131-e15131 ◽  
Author(s):  
Camilla Stedstrup Mosgaard ◽  
Mathias Holsey Gramkow ◽  
Christian Dehlendorff ◽  
Dorte Nielsen ◽  
Per Pfeiffer ◽  
...  

e15131 Background: CEA is regarded as the marker of choice for monitoring patients with colorectal cancer (CRC), but the value of using CA19-9 is insufficient. The prognostic value of serum CA19-9 in combination with CEA was evaluated in patients with metastatic CRC (mCRC) before first (1) and third line therapy (3LT). Methods: From April 2004 to May 2015, pretreatment serum samples were collected from 160 and 255 patients with mCRC before 1LT and 3LT, respectively. Median age was 64 [range 33-87] and male/female ratio 243(59%)/172(41%). Serum CA19-9 was determined by routine chemiluminescent immunometric assay (normal range 0-37 KU/l). Progression-free survival (PFS) and overall (OS) crude, adjusted hazard ratios (HR) and corresponding 95% confidence intervals (CIs) were estimated using Cox regression analysis. CA19-9 and CEA were included as log2-transformed continuous variables and adjustment included mutually between CA19-9 and CEA in addition to primary tumor location, sex and age. Results: In 3LT median pretreatment CEA levels were higher than in 1LT (59 µg/l [IQR 14-288] vs. 23[6-153] P < 0.01) while CA19-9 values were similar (112 KU/l [23-626] vs. 98[19-390]). In patients treated with 3LT univariate analysis showed that high levels of CA19-9 and CEA were associated with short PFS (CA19-9: HR = 1.06, 95% CI 1.02-1.10, P < 0.01; CEA: HR = 1.05, 1.00-1.09, P = 0.04). In 1LT neither CA19-9 nor CEA were significantly associated with PFS. In a multivariate analysis, none of the biomarkers were significantly associated with PFS. In patients treated with 3LT univariate analysis showed that high levels of CA 19-9 and CEA were associated with short OS (CA19-9: HR = 1.11, 1.07-1.16, P < 0.01; CEA: HR = 1.1, 1.06-1.16, P < 0.01). In patients treated with 1LT high levels of CA-19-9 but not CEA was significantly associated with a shorter OS (HR = 1.07, 1.00-1.14, P = 0.04). In 3LT multivariate analyses showed that high levels of CA19-9 and CEA were the only factors associated with a shorter OS (CA19-9: HR = 1.08, 1.03-1.13, P < 0.01; CEA: HR = 1.07, 1.01-1.14, P < 0.01), while there was no significant association to OS in 1LT. Conclusions: Serum CA19-9 may be a valuable prognostic biomarker in combination with CEA in mCRC patients receiving third line therapy.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4103-4103
Author(s):  
Mohsin Soleja ◽  
Suleyman Yasin Goksu ◽  
Nina Niu Sanford ◽  
Muhammad Shaalan Beg ◽  
Radhika Kainthla ◽  
...  

4103 Background: Prior studies have observed under-utilization of adjuvant chemotherapy (ACT) in stage III colon cancer. Our aims were to observe the rate of utilization of ACT in very healthy or “ideal candidates”, identify reasons for omission and socioeconomic factors associated with ACT use, and observe patient outcomes. Methods: We queried patients from the National Cancer Database (NCDB) with stage III colon cancer, age<65, and Charlson-Deyo score of 0 who underwent resection in the United States between 2004-2015. Patients who received ACT were compared to patients who had surgery only (SO). We used chi-square test for categorical variables, Kaplan-Meier and Cox regression method for survival analyses. Results: Out of 243,388 stage III colon cancer patients during the study time, a total of 49,046 patients met the specific criteria of “ideal candidate”. Out of these, 88.5% received ACT and 11.5% underwent SO. The primary reason for chemotherapy omission was: no reason given (54.2%), patient/guardian refusal (26.7%), physician recommended against (9.3%), patient died (3%), unknown (6.7%). Patients who received ACT were more likely to be female, non-Hispanic white, have a higher level of education, travel shorter distance for cancer treatment, have private insurance or higher income as compared to counterpart ( all p<.001). Patients who received ACT had significantly better overall survival (5-year survival rate 74% vs. 54%, p<.001). This persisted after multivariable Cox regression analysis [HR:0.48 (CI:0.45-0.50), p<.001]. Conclusions: We observed a high rate of utilization (88.5%) of ACT in patients with stage III colon cancer who were under age 65 and without comorbidities. However, the omission of chemotherapy in this population remains a problem, partially due to patient refusal. Socioeconomic factors associated with lower utilization were primarily related to insurance status (private vs non-private). Patients who received ACT had significantly improved survival as compared to SO group. [Table: see text]


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 361-361
Author(s):  
Tobias Robert Chapman ◽  
Stephen R. Bowen ◽  
Matthew J. Nyflot ◽  
Smith Apisarnthanarax

361 Background: Radiation induced liver disease (RILD) is of critical concern in the treatment of hepatocellular carcinoma (HCC) with radiation therapy (RT). Variability exists in metrics used to define RILD with no consensus on which best predict for overall survival (OS) and RILD-specific survival (RILDSS). We examined the correlation between toxicity metrics and clinical outcomes in a heavily pre-treated population that received RT. Methods: The charts of 37 HCC patients treated from 2013 - 2015 were reviewed retrospectively. At baseline, 62% were Child-Pugh (CP)-A, 32% CP-B and 5% CP-C. The majority (59%) had prior liver-directed therapy (LDT), 43% received stereotactic body RT and 49% proton RT. Pre-treatment, toxicity ( ≤ 6 months from treatment) and outcomes data were collected. Deaths from RILD were scored. Pre-treatment factors and toxicity outcomes were assessed by univariate Cox models for association with OS and RILDSS. Statistically significant predictors formed the basis for stepwise multivariate Cox regression to retain independent predictors of survival. Results: At a median follow-up of 8 months, 14 patients had an increase in CP score ( ≥ 2, n = 7) and 3 had ≥ G3 RTOG transaminitis. There were 11 deaths, 5 from RILD. On univariate analysis (UA), tumor size, pre-treatment liver function, prior LDT and 5 toxicity metrics (CP score increases and transaminitis) were significantly associated with OS. An increase of ≥ 1 CP score (HR 22.7, p = 0.005), pre-treatment ALBI grade (HR 6.0, p = 0.02) and tumor size (HR 1.2, p = 0.01) were independent predictors of OS on multivariate analysis (MVA). Similar factors were associated with RILDSS on UA, including ≥ 2 CP score increase and ≥ G3 ALT elevation; however, only pre-treatment CP score (HR 4.0, p = 0.01) and tumor size (HR 1.5, p = 0.03) were independently predictive on MVA. Conclusions: Pre-treatment liver functional status and tumor size were highly predictive of OS and RILDSS, suggesting that baseline functional hepatic reserve is the primary determinant in developing fatal RILD rather than post-RT changes in liver function. Further work is needed to define dosimetric parameters and pre-treatment factors that predict RILD toxicity.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 540-540
Author(s):  
Ravi Ramjeesingh ◽  
Amie Jones ◽  
Christine Orr ◽  
Corey Sean Bricks ◽  
Wilma M Hopman ◽  
...  

540 Background: Thrombocytosis has been identified as a prognostic factor in many cancer types including ovarian, breast, and lung cancers. In colorectal cancer (CRC), the literature is divided. Several smaller case studies suggest a negative prognosis in CRC patients with pre-operative thrombocytosis, a larger population study contradicts this. Methods: We performed a retrospective chart review of CRC patients treated at the Cancer Center of Southeastern Ontario diagnosed from January 2005 to December 2011. 1304 confirmed CRC patient charts were identified and patient, tumor, blood work and treatment variables were extracted. Results: 1,096 patients had platelet count available at the time of oncology consult. 222 (20.3%) were characterized as having thrombocytosis (>400x109/L). No difference was identified between those with normal and with thrombocytosis with regards to age, sex, comorbidities, and BMI. However, a statistically significant difference was identified when looking at several pathological characteristics. Significantly more patients with thrombocytosis presented with stage 4 disease (p<0.0001). Additionally less early T-stage (T1: p<0.05, T2: p<0.001), lymph node positivity (p<0.05) and LVI (p<0.05) was identified. Univariate analysis identified a significant difference in survival (1yr: 71.6% vs 88.1%, p<0.0001; 2 yr: 58.1% vs 78.1%, p<0.0001; 5yr: 48.2% vs 64.7%, p<0.0001). Multivariate Cox regression analysis, identified a statistically significant effect of thrombocytosis on risk of dying (HR=1.434, C.I 1.153-1.784, p=0.001). A survival difference was primarily identified in the Stage 4 population (1yr: 55.8% with thrombocytosis vs 72.9% with normal platelet count, p=0.0058; 2 yr: 36.0% vs 50.2%, p=0.0388; 5yr: 26.7% vs 32.0%, p=0.4042). There were no differences in the number of metastatic sites or the number of days on chemotherapy to account for the survival difference. Conclusions: Thrombocytosis, at the time of oncology consultation appears to predict a lower chance of survival in CRC patients, especially in the stage 4 population. Further work is required to elucidate the mechanism of action between elevated platelet counts and survival.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15060-e15060
Author(s):  
Benny Vittrup Jensen ◽  
Mathias Holsey Gramkow ◽  
Camilla Stedstrup Mosgaard ◽  
Christian Dehlendorff ◽  
Per Pfeiffer ◽  
...  

e15060 Background: The prognostic value of serum IL-6, YKL-40 and CEA before first (1) and third line therapy (3LT) in metastatic colorectal cancer (mCRC) is lacking and was evaluated in this study. Methods: From 2004 to 2015 serum samples were collected from 160 and 255 patients with mCRC before 1LT and 3LT, respectively. Median age was 64 years (range 33-87) and male/female ratio 243(59%)/172(41%). Serum IL-6 (R&D, UK) and YKL-40 (Quidel, USA) were determined by ELISA. Progression-free (PFS) and overall survival (OS), crude and adjusted hazard ratios (HR) and corresponding 95% confidence intervals (CI) were estimated with Cox regression analysis. CEA, IL-6 and YKL-40 were included as log2-transformed continuous variables with mutual adjustment between CEA, IL-6 and YKL-40, primary tumor location, sex and age. Results: In 3LT IL-6, YKL-40 and CEA levels were higher (P < 0.001) than in 1LT (IL-6: 9.5 pg/ml [IQR4.2-18.5] vs. 4.6 [2.5-10.5]; YKL-40: 140 ng/ml [77-272] vs. 101 [62-172]; and CEA: 59 ug/l [14-288] vs. 23[5.8-153]). In 3LT univariate analysis showed that increased levels of IL-6, YKL-40 and CEA were associated with shorter PFS (IL-6: HR = 1.19, 95% CI 1.07-1.31, P < 0.01; YKL-40: HR = 1.13, 1.04-1.24, P = 0.01; CEA: HR = 1.05, 1.00-1.09, P = 0.04). In 1LT only high IL-6 was associated with shorter PFS (HR = 1.09, 1.01-1.17, P = 0.03). In a multivariate analysis only high IL-6 was significantly associated with shorter PFS in 3LT (HR = 1.15, 1.03-1.29, P < 0.01) and none of the biomarkers in 1LT. In 3LT univariate analysis showed that increased levels of all 3 biomarkers were associated with a shorter OS (IL-6: HR = 1.36, 1.23-1.51, P < 0.01; YKL-40: HR = 1.21, 1.10-1.33, P < 0.01; CEA: HR = 1.11, 1.06-1.16, P < 0.01). In 1LT high levels of IL-6 (HR = 1.17, 1.08-1.27, P < 0.01) and YKL-40 (HR = 1.18, 1.00-1.38, P = 0.05), but not CEA, were associated with short OS. In 3LT the multivariate analysis showed that both higher IL-6 (HR = 1.34, 1.20-1.50, P < 0.01) and CEA (HR = 1.09, 1.03-1.14, P < 0.01), but not YKL-40 were significantly associated with a shorter OS. In 1LT only higher IL-6 was associated with a shorter OS (HR = 1.19, 1.08-1.31, P < 0.01) Conclusions: Serum IL-6 and YKL-40 may be useful prognostic biomarkers in combination with CEA in patients with mCRC


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