Impact of tumor site on the prognosis of small bowel adenocarcinoma

2019 ◽  
Vol 105 (6) ◽  
pp. 524-528 ◽  
Author(s):  
Rosa Falcone ◽  
Adriana Romiti ◽  
Marco Filetti ◽  
Michela Roberto ◽  
Riccardo Righini ◽  
...  
Keyword(s):  
Small Bowel ◽  
Clinical Outcome ◽  
Primary Tumor ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Rank Test ◽  
Small Bowel Adenocarcinoma ◽  
Tumor Site ◽  
Primary Tumor Site ◽  
Early Stage Disease

Background: Because of a lack of large-scale prospective studies there is no clear indication about the management of patients with small bowel adenocarcinoma (SBA). This study evaluated clinical outcome of patients diagnosed with SBA at our institution. Methods: Clinicopathologic features, treatments, and clinical outcome of patients diagnosed with SBA between 2006 and 2017 were retrospectively analyzed. Median time of survival was calculated and compared using the log-rank test. Multivariate Cox regression was used to test independence of significant factors in univariate analysis. Results: Forty patients were included in the study; the majority (82.5%) had a tumor in the duodenum (including ampulla of Vater) and an early stage disease at the diagnosis. Median overall survival (OS) in the whole study population was 26.5 months. Patients with a tumor of the lower part of the small intestine (jejunum, ileum, and appendix) showed a better OS compared with that of patients with upper SBA (40 months vs 26 months, respectively; P=0.09). Primary tumor site and stage were independent predictors of OS. Conclusions: Our results suggest a prognostic role for the primary tumor site. This finding deserves to be further investigated to ensure better classification as well as more effective management strategies for SBA.

A phase II study of 5-FU/l-LV/oxaliplatin (mFOLFOX6) in patients with metastatic or unresectable small bowel adenocarcinoma: A post hoc analysis.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 430-430
Author(s):  
Taro Funakoshi ◽  
Takahiro Horimatsu ◽  
Norisuke Nakayama ◽  
Toshikazu Moriwaki ◽  
Yoshinori Hirashima ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Small Bowel ◽  
Primary Tumor ◽  
Performance Status ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Primary Site ◽  
Small Bowel Adenocarcinoma ◽  
Serum Cea ◽  
Post Hoc

430 Background: Small bowel adenocarcinoma (SBA) is a rare disease. Previous studies suggested several prognostic factors of unresectable SBA, including age, performance status (PS), primary site, resection of primary tumor, histology, and tumor marker (CEA and CA19–9) levels. However, prognostic factors of the patients treated with oxaliplatin–fluoropyrimidine combination therapy were unknown, while these drugs were reported as a promising chemotherapy regimen for SBA. Methods: Previously untreated SBA patients were treated with an mFOLFOX6 regimen, and a post hoc analyses for prognostic factors were performed. Results: Between April 2010 and November 2012, 24 patients were included in this study. The overall response rate was 45% (9/20). The median progression-free survival and overall survival (OS) were 5.4 months (95% CI, 4.8–6.0) and 17.3 months (95% CI, 11.7–19.0), respectively. Univariate analysis revealed that lower PS (HR= 0.27; 95% CI, 0.10–0.77; p= 0.014), primary disease of the jejunum (HR= 0.35; 95% CI, 0.11–1.12; p=0.077), and serum CEA in the normal range (HR= 0.40; 95% CI, 0.14–1.11; p= 0.079) were potential prognostic factors of longer OS (threshold, p< 0.10). Although resection of the primary tumor was not a predictive factor of survival in this study, 54% and 21% of the patients needed surgery (primary resection or bypass) because of stenosis before and during chemotherapy, respectively. It is considered that bowel obstruction should be addressed before and during treatment. Conclusions: PS, primary site, and serum CEA levels are potential prognostic factors of unresectable SBA. There is a higher incidence of bowel stenosis or obstruction caused by the primary tumor before and during the treatment of SBA.

Analysis of prognostic factors in advanced pancreatic cancer (APDAC) patients (pts) undergoing to first-line nab-paclitaxel (Nab-P) and gemcitabine (G) treatment.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 412-412 ◽  
Author(s):  
Guido Giordano ◽  
Vanja Vaccaro ◽  
Eleonora Lucchini ◽  
Paola Bertocchi ◽  
Francesca Bergamo ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Primary Tumor ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Advanced Pancreatic Cancer ◽  
Prognostic Impact ◽  
First Line ◽  
Primary Tumor Site ◽  
Clinical Records ◽  
Ecog Ps

412 Background: Nab-P + G combination represents an optimal first line therapeutic option in APDAC. Actually we have no parameters to predict prognosis in pts receiving this regimen. Here we present data of a multicentre retrospective analysis evaluating prognostic impact of clinical or biological factors in a cohort of APDAC pts treated with Nab-P + G first line CT. Methods: Clinical records of 118 APDAC pts receiving first line Nab-P + G were retrospectively reviewed. Overall survival (OS) and progression free survival (PFS) were evaluated with Kaplan Meier method with 95% CI and curves were compared with log-rank test. Cox-regression model was applied to the data with univariate and multivariate approach. Variables included in analysis were age, gender, ECOG PS, primary tumor site, liver metastases, multiple metastatic sites, baseline CA19-9, bilirubin levels, neutrophil/lymphocyte ratio (NLR), CA19-9 decrease > 50%, biliary stent and symptomatic disease. Results: Median age was 66 (37 - 83), M/F:65/53, ECOG PS 0/1/2: 51/46/21 respectively. 4 complete and 27 partial responses were observed with 26% response rate (RR). Median OS and PFS were 11 months (95% CI 9.58 – 12.41) and 7 months ( 95% CI 5.96 – 8.03) respectively. When considered at univariate analysis primary tumor location to the head, ECOG PS of 2, bilirubin levels higher than median and NLR ≥ 5 had a bad prognostic impact both on PFS and OS. Differently, CA19-9 decrease > 50% was considered a positive prognostic factor for PFS and OS. Multivariate analysis confirmed the negative role of NLR ≥ 5 respect of PFS (HR 3.21; 95%CI 1.61 – 5.68, p = 0.002) and OS (HR 3.38; 95%CI 1.88 – 5.79, p = 0.001) and positive impact of CA19-9 decrease > 50% on PFS (HR 0.37; 95% CI 0.11 – 0.68, p=0.006) and OS (HR 0.53; 95% CI 0.15 – 0.97, p=0.005), as independent prognostic factors. Conclusions: This analysis suggest that in APDAC pts receiving first line Nab-P + G, high NLR value (≥5) could be considered an easy detectable, independent parameter to predict poor outcomes in terms of PFS and OS. Furthermore CA19-9 reduction > 50% from baseline may be, in absence of other clinical and molecular parameters, an early marker of good prognosis.

Patterns of metastasis and second primary malignancies (SPM) in colorectal cancer: A perspective from Peru.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15068-e15068
Author(s):  
Jorge Leon ◽  
Fernando Namuche ◽  
Paola Catherine Montenegro ◽  
Claudio J. Flores
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Disease ◽  
Biological Therapy ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Rank Test ◽  
Second Primary ◽  
Primary Tumor Site ◽  
Metastatic Setting ◽  
Second Primary Malignancies

e15068 Background: The incidence of colorectal cancer (CRC) in Peru has increased in the last decades. Approximately 20% of patients with CRC already have metastases at diagnosis, and this figure has been stable over the last two decades. The lack of data makes it more difficult to manage our patients. The metastatic setting and patients with second primary malignancies are complicated scenarios. The objective of our study was to explore and describe the metastasis patterns and the second primary malignancies’ frequency in CRC patients. Methods: We retrospectively reviewed the electronic medical records of 609 patients with CRC from one specialized Peruvian cancer center between 2006 and 2016. For the evaluation of the metastasis pattern, we selected 198 patients with metastasis at debut and the patients who had relapse of the disease. Descriptive results for numeric variables were presented as means with standard deviation (SD) or medians with interquartile range (IQR), depending on their distributions; otherwise, we expressed the qualitative variables as numbers with percentages. We evaluated the metastasis pattern according to primary tumour sidedness, age, CEA, histological grade, histological type. A survival analysis was performed with Kaplan Meier method, comparing the curves with Log Rank test for metastasectomy, biological therapy and number of sites with metastatic disease. A multivariate analysis was performed using the Cox regression model with the statistically significant variables found in the univariate analysis. Results: At the time of diagnosis, stage IV disease accounted for 15.3% (93) of all CRC cases. 105 (stage I-III) pts had relapse disease. Regardless of the primary tumor site, the most common site for metastatic spread was the liver (42.9%), lung (12.6%), carcinomatosis (18.2%). Pts who underwent metastasectomy presented a better OS [HR, 0.284; 95% CI, 0.123-0.657; p < 0.05], as well as pts who received biologic therapy [HR, 0.641; 95% CI, 0.416-0.990; p < 0.05] and a greater number of sites with metastatic disease had worst OS [HR, 1.878; 95% CI, 1.181-2.985; p < 0.05] The incidence of SPM following CRC was 48/609 (7.8%), the more frequent localizations were: breast, prostate and lung with 14.6% each, then kidney 10.4%, bladder 8.3%. Conclusions: In mCRC metastasectomy, biological therapy and number of sites with metastatic disease play an important role in OS. The more frequent localizations with SPM were breast, prostate and lung.

scholarly journals Clinical Profiles and Survival Outcomes of Patients With Well-Differentiated Neuroendocrine Tumors at a Health Network in New South Wales, Australia: Retrospective Study

JMIR Cancer ◽  
10.2196/12849 ◽  
2019 ◽  
Vol 5 (2) ◽  
pp. e12849
Author(s):  
Jocelyn Reeders ◽  
Vivek Ashoka Menon ◽  
Anita Mani ◽  
Mathew George
Keyword(s):  
Survival Rate ◽  
Neuroendocrine Tumors ◽  
Primary Tumor ◽  
Univariate Analysis ◽  
Survival Outcomes ◽  
Tumor Site ◽  
Primary Tumor Site ◽  
Clinical Profiles ◽  
Well Differentiated ◽  
Related Mortality

Background Neuroendocrine tumors (NETs) are a heterogeneous group of malignancies with varying and often indolent clinicobiological characteristics according to their primary location. NETs can affect any organ and hence present with nonspecific symptoms that can lead to a delay in diagnosis. The incidence of NETs is increasing in Australia; data regarding characteristics of NETs were collected from the cancer registry of Hunter New England, Australia. Objective This study aimed to explore the clinical profiles and treatment and survival outcomes of patients with well-differentiated NETs in an Australian population. Methods We reviewed the data of all adult patients who received the diagnosis of NET between 2008 and 2013. The clinicopathological, treatment, and follow-up data were extracted from the local Cancer Clinical Registry. We also recorded the level of remoteness for each patient by matching the patient’s residential postcode to the corresponding Australian Bureau of Statistics 2011 remoteness area category. Univariate analysis was used to find the factors associated with NET-related mortality. Survival analysis was computed. Results Data from 96 patients were included in the study (men: 37/96, 38.5%, and women: 59/96, 61.5%). The median age at diagnosis was approximately 63 years. A higher proportion of patients lived in remote/rural areas (50/96, 52.1%) compared with those living in city/metropolitan regions (46/96, 47.9%). The most common primary tumor site was the gastroenteropancreatic tract, followed by the lung. The factors significantly associated with NET-related mortality were age, primary tumor site, surgical resection status, tumor grade, and clinical stage of the patient. At 5 years, the overall survival rate was found to be 62%, and the disease-free survival rate was 56.5%. Conclusions Older age, advanced unresectable tumors, evidence of metastasis, and higher-grade tumors were associated with poorer outcomes. Lung tumors had a higher risk of NET-related mortality compared with other sites.

scholarly journals Clinical Profiles and Survival Outcomes of Patients With Well-Differentiated Neuroendocrine Tumors at a Health Network in New South Wales, Australia: Retrospective Study (Preprint)

2018 ◽  
Author(s):  
Jocelyn Reeders ◽  
Vivek Ashoka Menon ◽  
Anita Mani ◽  
Mathew George
Keyword(s):  
Survival Rate ◽  
Neuroendocrine Tumors ◽  
Primary Tumor ◽  
Univariate Analysis ◽  
Survival Outcomes ◽  
Tumor Site ◽  
Primary Tumor Site ◽  
Clinical Profiles ◽  
Well Differentiated ◽  
Related Mortality

BACKGROUND Neuroendocrine tumors (NETs) are a heterogeneous group of malignancies with varying and often indolent clinicobiological characteristics according to their primary location. NETs can affect any organ and hence present with nonspecific symptoms that can lead to a delay in diagnosis. The incidence of NETs is increasing in Australia; data regarding characteristics of NETs were collected from the cancer registry of Hunter New England, Australia. OBJECTIVE This study aimed to explore the clinical profiles and treatment and survival outcomes of patients with well-differentiated NETs in an Australian population. METHODS We reviewed the data of all adult patients who received the diagnosis of NET between 2008 and 2013. The clinicopathological, treatment, and follow-up data were extracted from the local Cancer Clinical Registry. We also recorded the level of remoteness for each patient by matching the patient’s residential postcode to the corresponding Australian Bureau of Statistics 2011 remoteness area category. Univariate analysis was used to find the factors associated with NET-related mortality. Survival analysis was computed. RESULTS Data from 96 patients were included in the study (men: 37/96, 38.5%, and women: 59/96, 61.5%). The median age at diagnosis was approximately 63 years. A higher proportion of patients lived in remote/rural areas (50/96, 52.1%) compared with those living in city/metropolitan regions (46/96, 47.9%). The most common primary tumor site was the gastroenteropancreatic tract, followed by the lung. The factors significantly associated with NET-related mortality were age, primary tumor site, surgical resection status, tumor grade, and clinical stage of the patient. At 5 years, the overall survival rate was found to be 62%, and the disease-free survival rate was 56.5%. CONCLUSIONS Older age, advanced unresectable tumors, evidence of metastasis, and higher-grade tumors were associated with poorer outcomes. Lung tumors had a higher risk of NET-related mortality compared with other sites.

Fifteen-year experience of all patients (pts) with small bowel adenocarcinoma (SBA), treated in a specialized gastrointestinal (GI) oncology unit: Royal Marsden (RM) experience.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 316-316
Author(s):  
Khurum Hayat Khan ◽  
Clare Peckitt ◽  
Francesco Sclafani ◽  
Sachin Trivedi ◽  
Vikram Kumar Jain ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Small Bowel ◽  
Advanced Disease ◽  
Early Stage ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Small Bowel Adenocarcinoma ◽  
Early Stage Disease ◽  
Free Survival ◽  
Resectable Disease

316 Background: Small bowel adenocarcinoma (SBA) is a rare tumour with poor prognosis. There is paucity of published literature due to rarity of disease; we conducted this retrospective study to determine the clinical course and outcome along with prognostic factors in both early and later stage SBA. Methods: Clinical characteristics and outcomes of all pts treated consecutively in the GI Unit RM, 1996-2011 were recorded. The study endpoints were relapse free survival (RFS), progression free survival (PFS), and overall survival (OS), in early stage pts (G1) and in pts with advanced disease (presentation or relapse with un-resectable disease=G2). In G2 response rate (RR) to chemotherapy was determined. In both groups association to baseline prognostic factors were sought by performing Cox regression univariate analysis (UVA). Results: Eighty four pts with SBA were treated 1996-2011. A total of 48 presented with early stage disease (G1). In G1 (58.3% males; mean age, 57 years), 44/48 pts underwent R0 resection; 21 received adjuvant chemotherapy. RFS, PFS and OS in this group were 29.6 [95% confidence interval (CI) 3.3-55.9], 31.1 (CI=8.0-54.3) and 42.9 (CI=0-94.9) months (m), with median follow up of 76.4 m. Poor histological differentiation (p=0.025), abnormal CEA at presentation (P=0.082), and lymphovascular invasion (p=0.003) were prognostic of OS. G2 comprised of 36 pts with un-resectable disease along with 23 from G1 who subsequently relapsed [G2 (n=59); 52.5% males; mean age, 59 years]; 54 pts with metastatic and 5 with locally advanced disease; 78% received first-line chemotherapy. Overall RR of pts who received chemotherapy was 50%. OS and PFS were 12.8 (CI =8.4-17.2) and 8.8 (CI=5.5-12.3) m respectively; 1-year survival was 60.9% vs. 27.3% (no chemotherapy) (p=0.042). Abnormal albumin (0.041), platelet count (p=0.007) and CEA (p=0.025) were prognostic of OS in the chemotherapy group; doublet (18/41) versus triplet (23/41) chemotherapy were not prognostic (p=0.185). Conclusions: Pts with SBA and metastatic disease may derive benefit from systemic chemotherapy; prospective clinical trials are required to evaluate this further.

Efficacy of third-line anti-EGFR-based treatment (tx) versus (vs) Regorafenib/TAS-102 (R/T) according to primary tumor site in RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) patients (pts).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4082-4082
Author(s):  
Raffaella Vivolo ◽  
Emilio Bria ◽  
Ina Valeria Zurlo ◽  
Maria Bensi ◽  
Emanuela Dell'Aquila ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Statistical Significance ◽  
Phase Iii ◽  
Rank Test ◽  
Tumor Site ◽  
Primary Tumor Site ◽  
Exact Test ◽  
Molecular Features ◽  
Third Line ◽  
Few Data

4082 Background: Right- (R) and left-sided (L) mCRCs exhibit different clinical and molecular features. Several retrospective analyses showed that the survival benefit of anti-EGFR-based tx is limited to RAS/BRAF wt L-sided mCRC pts, which a larger effect in the first-line setting. Few data are available concerning the anti-EGFR efficacy according to primary tumor site in third line. Methods: Pts affected by RAS/BRAF wt mCRC treated with third-line anti-EGFR-based tx or R/T were retrospectively collected. The objective of the analysis was to compare tx activity and efficacy according to tumor site. Primary endpoint was PFS; secondary endpoints were OS and RR. PFS and OS analyses were performed using Kaplan-Meier method, and survival curves were compared using the log-rank test. RR was evaluated according to RECIST criteria and it was compared in the two groups using Fisher’s exact test. Statistical significance was set at p = 0.05 for a bilateral test. Univariate and multivariate analyses for PFS and OS were performed. Results: A total of 76 RAS/BRAF wt mCRC pts, treated with third-line anti-EGFR-based tx or R/T, were enrolled. Of those, 19 (25%) pts had R-sided tumor (9 pts received anti-EGFR tx and 10 pts received R/T) and 57 (75%) pts had L-sided tumor (30 pts received anti-EGFR tx and 27 pts received R/T). As shown in the table, a significant PFS and OS benefit in favor of anti-EGFR tx vs R/T was observed in L-sided pts, while no difference both in PFS and OS was observed in R-sided pts. RR was significantly higher in L-sided pts treated with anti-EGFR vs R/T, no difference was shown in R-sided pts. At the multivariate analysis, tx regimen was indipendently associated with PFS in L-sided pts, but not in R-sided pts. Conclusions: Our study confirmed the results deriving from the retrospective analysis of the phase III study 20020408. Our results demonstrated a different benefit from third-line anti-EGFR tx according to primary tumor site, confirming the role of L-sided tumor in predicting benefit from third-line anti-EGFR vs R/T, while no difference was observed in R-sided tumors. [Table: see text]

scholarly journals The Correlation Analysis of Baseline Serum CA199, CEA and CA125 in Patients with Advanced Pancreatic Cancer

2020 ◽  
Author(s):  
Guochao Deng ◽  
Huan Yan ◽  
Zhipeng Guo ◽  
Guanghai Dai
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Markers ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Advanced Pancreatic Cancer ◽  
Rank Test ◽  
Fisher Exact Test ◽  
Primary Tumor Site ◽  
Baseline Serum ◽  
The Relationship

Abstract Background:CA199, CEA and CA125 were the most widely used tumor markers in pancreatic cancer. However, the studies associated with the relationship between the three markers and pancreatic cancer were limited. This study aimed to explore the correlation between baseline serum CA199, CEA, CA125 levels and clinical characteristics in pancreatic cancer. Methods:278 patients with advanced pancreatic cancer received first-line chemotherapy treatments enrolled in this research. Correlated analysis between tumor markers and disease characteristics was performed by Pearson’s Chi-squared test or Fisher exact test. We used Pearson’s correlation test to investigate the relationship between tumor markers and peripheral blood parameters. Univariate analysis was estimated by Kaplan-Meier method and compared using the log-rank test. Multivariate analysis and HR calculation was determined by the Cox regression model. Results: Baseline CA199, CEA, and CA125 both positively associated with the primary tumor site (p=0.007; p=0.012; p=0.003, respectively);liver metastasis (p=0.001; p=0.001; p=0.028, respectively); number of organ metastasis (p=0.001; p=0.008;p=0.042, respectively); baseline WBC levels (p<0.001; p<0.001; p<0.001, respectively), LDH levels (p<0.001; p=0.004; p<0.001, respectively). And CA199 also correlated with years of smoking(p=0.024); diabetes and year of diabetes (p=0.012; p=0.012); baseline glycemic levels (p=0.004). CA199 and CA125 levels had the relationship with baseline neutrophil counts (p<0.001; p<0.001, respectively). Years of smoking, baseline neutrophil counts, LDH levels, CA199 levels and CA125 levels were independent prognostic factors. Conclusion: Combinations of the four factors were also correlated with survival. It’s concluded that CA199, CEA, CA125 correlated with multi-factors of clinical factors. And combinations of baseline neutrophil counts, LDH levels, CA199 levels and CA125 levels were also prognostic factor.

Serum matrilysin (MMP7) levels are associated with progression, in curatively resected colorectal cancer (CRC) patients

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4124-4124 ◽  
Author(s):  
A. Martinez-Fernandez ◽  
E. Pineda ◽  
L. Visa ◽  
X. Garcia-Albeniz ◽  
J. Auge ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastases ◽  
Primary Tumor ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Early Stage Disease ◽  
Cox Regression Analysis ◽  
Node Metastases

4124 Background: Matrilysin (MMP7) has been shown to be over-expressed in CRC, specially in liver metastases. Additionally MMP7 over-expression in primary tumor, predict metastatic potential in early-stage disease (Gut 12:1751;2005). As the activated pro-domain, could be detected in serum by ELISA method, we search if it could also identify a subgroup of non-metastatic CRC patients with a higher risk of relapse. Methods: Serum MMP7 (S-MMP7) was measured by commercially available ELISA, in 92 healthy controls and 175 consecutive patients before undergoing laparoscopy-assisted or open curative resection for CRC, between July 2003 to December 2004. Clinic- pathologic variables were tested for their effect on disease-free survival (DFS) in univariate and multivariate Cox regression analysis. Results: S-MMP7 levels were significantly higher in CRC patients than in controls (p=0.02). Mean age in CRC patients was 71 years (range 31–90). Median nodal retrieval was 14 (range 0–47). The median S-MMP7 (4.9 ng/ml) was chosen for cut-off value. After a median follow- up of 26 months, the rate of DFS was 72%. Univariate analysis identified high S-MMP7 levels, CEA concentration, age, extent of primary tumor and lymph-node metastases as variables associated with DFS. Multivariate analysis identified lymph-node metastases (OR.1,88, p=0.046) and S-MMP7 (OR.1,103, p=0.039) as independent prognostics factors. Conclusions: With a short follow-up, S-MMP7 levels predict recurrence in curatively resected CRC. As a subset of these patients could be managed with secondary liver resection, S-MMP7 determination would be particularly warranted for more intensive surveillance strategies. No significant financial relationships to disclose.

Association of HER2 and IGF1 germline polymorphisms with outcome in metastatic colorectal cancer (mCRC) patients (pts) treated with second-line irinotecan (IR) with or without cetuximab (CB): The EPIC experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3615-3615 ◽  
Author(s):  
Dongyun Yang ◽  
Pierre Oliver Bohanes ◽  
Wu Zhang ◽  
Christopher Harbison ◽  
Ovidiu C. Trifan ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Rank Test ◽  
Second Line ◽  
Exact Test ◽  
Fisher's Exact Test ◽  
Fisher’S Exact Test

3615 Background: EPIC, a multinational phase III clinical trial with IR + CB vs IR alone in mCRC pts in the second-line setting after failure of FOLFOX demonstrated a benefit for IR+CB in progression-free survival (PFS) and response rate (RR). We evaluated 6 functional germline polymorphisms involved in the IGF1 and HER2 for their potential role as molecular predictors of clinical outcome in pts treated in the EPIC study. Methods: DNA was extracted from all available formalin-fixed paraffin-embedded tumor samples from the EPIC trial. Genotyping was performed using PCR-RFLP assays and 5’ -end [g-33P] ATP’ labeled PCR-protocols. Univariate analysis (Fisher's exact test for RR; log-rank test for PFS and OS) was performed to examine associations between polymorphisms and clinical outcome. Multivariate analysis (Logistic regression or Cox regression model) was conducted to control baseline patient characteristics and treatment. Results: 186 pts with available samples were treated either with IR/CB (arm A, 84 pts) or IR alone (arm B, 102 pts). Median age was 59 yrs (range 34-85yrs) for arm A and 61 yrs (range 25-90 yrs) for arm B. In arm A, 11/84 pts (13%) showed CR or PR, whereas 73/84 (87%) pts had SD or PD. For arm B, 6/102 pts (6%) showed CR or PR, whereas 96/102 pts (94%) had SD or PD. Median PFS for arm A was 3.0 months (95%CI 2.4- 4.1 months) vs 2.7 months (95%CI 2.2-2.9 months) for arm B; median OS was 9.3 months (95%CI 7.1-21.1 months) for arm A vs 12.3 months (95%CI 10.4- 17.9 months) for arm B. KRAS mutation status was not significantly associated with outcome in our patient cohort. We found that HER2 rs 1136201 was significantly associated with response (RR: AA 6.5%, AG 12.5%, and GG 27.3%, Fisher’s exact test p=0.045). IGF1 rs 2946834 was significantly associated with PFS in both univariate and multivariate analyses (median PFS was 2.8 months in patients with CC or CT vs 1.8 months in patients with TT; log-rank p=0.009; Wald test p=0.008). Conclusions: Our study suggests the prognostic value of polymorphisms in the IGF1 and HER2-pathway in mCRC pts treated with IR± CB. Prospective validation of these findings in clinical trials is warranted.

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