Use of sex-specific genomic profile to predict clinical outcome in metastatic colorectal cancer (mCRC) patients treated with 5- fluorouracil/oxaliplatin

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4122-4122 ◽  
Author(s):  
M. A. Gordon ◽  
W. Zhang ◽  
D. Yang ◽  
F. Nagashima ◽  
H. Chang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Outcome ◽  
Tumor Progression ◽  
Hormone Replacement ◽  
Regression Trees ◽  
Genetic Profile ◽  
Mthfr Polymorphisms ◽  
Cart Analysis ◽  
Males And Females ◽  
Time To Tumor Progression

4122 Background: There is increasing evidence that gender plays a significant role in the development and progression of colorectal cancer (CRC). Rates of CRC incidence are higher among males, and it has been shown that hormone replacement therapy in postmenopausal women reduces the risk of developing CRC, indicating a protective effect of female hormones. These findings indicate that physiological differences between the sexes may contribute to differential tumor development and progression. In the current study, we tested the hypothesis whether males and females would have different genomic profiles that would predict clinical outcome in 5-FU/oxal-treated mCRC. Methods: One hundred seventy-three patients were enrolled in this phase II study. One hundred fifty-two patients were evaluable for genotyping and statistical analysis. There were 74 females and 78 males, and median age was 60 (range 25–87). Twenty-four polymorphisms in 12 genes involved in cancer progression were tested by PCR. CART analysis was used to test for association of polymorphisms with overall survival (OS), time to tumor progression (TTP), and tumor response. Separate regression trees were developed for males and females. Results: Median follow-up was 18.6 months, response rate 19%, median time to tumor progression 4.2 months and median survival 10.3 months. CART analysis by gender generated significantly different regression trees for men versus women. For TTP, males carrying polymorphisms in the ER-β and SCN1A genes had improved TTP, while females carrying polymorphisms in the XPD and EGFR genes had improved TTP. For OS, male patients carrying ER-β and MTHFR polymorphisms had improved OS, while female patients carrying polymorphisms in SCN1A and PLA2 had improved OS. It is notable that analysis of males and females in combination produced a different regression tree than when separated by gender. Conclusions: Our results suggest for the first time that genomic profiling to predict clinical outcome of patients with mCRC depends on gender. Taking gender into account when examining the genetic profile of patients may help to more specifically identify those who will benefit from 5-FU/oxal chemotherapy. No significant financial relationships to disclose.

Polymorphisms in estrogen receptor beta, interleukin-8, and interleukin-8 receptor associated with clinical outcome in metastatic colorectal cancer (mCRC) patients treated with 5-fluorouracil/oxaliplatin

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4130-4130
Author(s):  
R. D. Ladner ◽  
M. A. Gordon ◽  
W. Zhang ◽  
D. Yang ◽  
F. Nagashima ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Estrogen Receptor ◽  
Clinical Outcome ◽  
Tumor Progression ◽  
Sex Hormones ◽  
Tumor Response ◽  
Estrogen Receptor Beta ◽  
Interleukin 8 ◽  
Receptor Beta ◽  
Time To Tumor Progression

4130 Background: Many factors contribute to the progression of colorectal cancer and to chemoresistance. Two factors that have recently gained attention are angiogenesis and sex hormones. Interleukin-8 and its receptors play a critical role in angiogenesis, and polymorphisms in these genes have previously been reported to predict clinical outcome and resistance to therapy in a variety of cancer types. In addition, gender and the subsequent varied levels of sex hormones between males and females may also have an impact on colorectal cancer progression. Sex hormones such as estrogen exert their effects on the cell by binding to steroid receptors such as estrogen receptor beta (ER-β). It is known that ER-β is predominantly expressed in the colon, and that differential expression of this gene is predictive of clinical outcome. Therefore, functional polymorphisms within ER-β, IL-8, and the IL-8 receptors may prove to be molecular markers for predicting clinical outcome in colorectal cancer patients. Methods: 173 patients were enrolled in this phase II study. 152 patients were evaluable for genotyping and statistical analysis. There were 74 females and 78 males, and median age was 60 (range 25–87). The dose of oxaliplatin was 130mg/m2 every 3 weeks and 5-FU was 200mg/m2/day CI for 10 weeks followed by 2 weeks rest. Polymorphisms in estrogen receptor beta, IL-8, and CXCR2 (IL-8 receptor) were tested by PCR. Results: Median follow-up was 18.6 months, response rate 19%, median time to tumor progression 4.2 months and median survival 10.3 months. IL-8 T251A polymorphism was predictive of time to tumor progression (p=0.04, log-rank test). ER-β CA repeat polymorphism was predictive of tumor response as well as time to tumor progression (p=0.015, p=0.012, respectively). ER-β A730G SNP was also predictive of time to tumor progression (p=0.03). Polymorphism in CXCR2 was predictive of tumor response (p=0.034). Conclusions: Our results suggest that polymorphisms within IL-8, CXCR2, and ER-β may affect the progression of colorectal cancer and subsequent clinical outcome. These results highlight the importance of angiogenesis and hormone levels in colorectal cancer. No significant financial relationships to disclose.

scholarly journals High expression of atonal homolog 8 predicts a poor clinical outcome in patients with colorectal cancer and contributes to tumor progression

2017 ◽  
Vol 37 (5) ◽  
pp. 2955-2963 ◽  
Author(s):  
Mengsi Ye ◽  
Yun He ◽  
Hao Lin ◽  
Shouxing Yang ◽  
Yuhui Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Outcome ◽  
Tumor Progression ◽  
High Expression ◽  
Poor Clinical Outcome

Polymorphisms of DNA-repair genes associated with clinical outcome in metastatic breast cancer (MBC) patients treated with gemcitabine/cisplatin (GC) (California Cancer Consortium)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 675-675
Author(s):  
M. A. Gordon ◽  
W. Zhang ◽  
D. Yang ◽  
D. Spicer ◽  
J. Doroshow ◽  
...  
Keyword(s):  
Overall Survival ◽  
Dna Repair ◽  
Clinical Outcome ◽  
Tumor Progression ◽  
Tumor Response ◽  
Dna Repair Genes ◽  
Repair Capacity ◽  
Repair Enzymes ◽  
Repair Genes ◽  
Time To Tumor Progression

675 Background: DNA repair enzymes may play an important role in determining efficacy of chemotherapy in MBC. In particular, GC combination therapy may be dependent on activity of DNA repair enzymes in host cells, since cisplatin acts by inducing DNA damage. Cancer cells with increased DNA repair capacity may be resistant to GC, and specific genes may be responsible for this increased repair capacity. We examined whether polymorphisms in genes related to DNA repair were associated with clinical outcome in MBC patients treated with GC, enrolled in a parent phase II clinical trial (Ph II-14 A & B). Methods: Fifty-five patients with MBC were evaluated. Patients received the following regimen: 25 mg/m2 cisplatin on days 1–4; 1000 mg/m2 gemcitabine on days 2 and 8 of 21-day cycle. Thirteen polymorphisms in 10 cancer-related genes were tested for association with overall survival, time to tumor progression, and tumor response using a PCR RFLP based assay. Results: Of 55 patients evaluated, there were 17 responders (31%) and 33 non-responders (60%). Five patients (9%) inevaluable for response. Of 33 non-responders, 15 had stable disease, 18 had progressive disease. Median survival: 11.7 months with median follow-up 32.4 months for 4 patients alive at time of analysis. Median progression-free survival: 4.2 months. XPD Lys751Gln polymorphism was associated with overall survival and time to tumor progression (p=0.0003, p=0.006, respectively, log-rank test). Thirty-five patients carried Lys/Lys genotype, of which 29% resopnded. Fourteen patients carried Lys/Gln genotype, of which 54% resopnded. Five patients carried Gln/Gln genotype, with no responders. XRCC3 Thr241Met polymorphism was associated with time to tumor progression and tumor response (p=0.03, p=0.002, respectively). Eighteen patients had Met/Met genotype, of which 47% responded. Twenty-six patients had heterozygous genotype, of which 17% responded. Five patients had homozygous Thr/Thr, of which 100% responded. Conclusions: Our results suggest that polymorphisms in DNA repair genes XPD and XRCC3 may be important markers in predicting clinical outcome in MBC patients treated with GC. Supported by the following NCI grant: N01 CM1701. [Table: see text]

Effect of increased body mass index on time to tumor progression in metastatic unresectable colorectal cancer patients treated with bevacizumab-based therapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14594-e14594
Author(s):  
Ibrahim Yildiz ◽  
Fatma Sen ◽  
Leyla Kilic ◽  
Serkan Keskin ◽  
Rumeysa Ciftci ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Body Mass Index ◽  
Tumor Progression ◽  
Cancer Patients ◽  
Combination Chemotherapy ◽  
Group A ◽  
Group B ◽  
High Bmi ◽  
Time To Tumor Progression

e14594 Background: High body mass index (BMI) is a well known risk factor in the development and recurrence of several solid tumors including colorectal cancer (CRC). Obesity is associated with increased serum levels of vascular endothelial growth factor (VEGF). Bevacizumab is the main targeted therapy inhibiting tumor angiogenesis by blocking VEGF receptor. We evaluated the effect of BMI on time to tumor progression (TTP) in patients who received bevacizumab based therapy due to advanced colorectal cancer in our institution. Methods: Patients with metastatic colorectal cancer who have been treated with fluoropyrimidine-based combination chemotherapy with bevacizumab were included in the study. Data of patients’ clinical treatment characteristics were obtained from the medical records. The height and weight measured during the initiation of bevacizumab were used to assign the patients to group A (BMI<25 kg/m2) and group B (BMI≥25 kg/m2). The time to tumor progression was defined as the day of initiation of bevacizumab based threpay to the date of first documented progressive disease, the date of death regardless of its course or the date of last follow up if no disease progression or no death occured at this time. Results: 236 patients (median age 57, range 27-79 years) were treated withfluoropyrimidine-based combination chemotherapy with bevacizumab between April 2007 and June 2011. 127 (51.3%) patients had a BMI <25 kg/m2 and 115 (48.7%) patients were found to have a BMI ≥25 kg/m2. One hundred ninety-three patients (82.1%) had first line bevacizumab therapy, and 44 patients (22.8%) had second-line bevacizumab therapy. Tumors of 68.4% of patients in group A and 69,1% of patients in group B progressed during a median 10 months (3-57 months) follow up. The median TTP was 9.5 months in the BMI <25 group and 8.2 months in the BMI >25 group.In multivariate analysis, high BMI (≥25 kg/m2) was associated with significantly shorter TTP (p: 0.002; HR, 1.91; 95% CI, 1.26–2.88). Conclusions: High BMI is a relevant prognostic factor in predicting the time to tumor progression in metastatic colon cancer patients treated with bevacizumab.

scholarly journals PD-0001 Can We Predict Time to Tumor Progression in Early Colorectal Cancer Patients Using CTCS Count?

2013 ◽  
Vol 24 ◽  
pp. iv25
Author(s):  
Michela Roberto ◽  
Adriana Romiti ◽  
Roberta Di Rocco ◽  
Salvatore Raffa ◽  
Danilo Ranieri ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Progression ◽  
Cancer Patients ◽  
Early Colorectal Cancer ◽  
Colorectal Cancer Patients ◽  
Time To Tumor Progression

Fish oil supplementation during chemotherapy increases posterior time to tumor progression in colorectal cancer

2015 ◽  
Vol 68 (1) ◽  
pp. 70-76 ◽  
Author(s):  
Carolina de Quadros Camargo ◽  
Michel Carlos Mocellin ◽  
Juliana de Aguiar Pastore Silva ◽  
Maria Emilia de Souza Fabre ◽  
Everson Araújo Nunes ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fish Oil ◽  
Tumor Progression ◽  
Fish Oil Supplementation ◽  
Time To Tumor Progression

Prognostic stratification of k-RAS wild type colorectal cancer patients receiving irinotecan-cetuximab treatment: Preliminary results of a prospective study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3591-3591
Author(s):  
Mario Scartozzi ◽  
Riccardo Giampieri ◽  
Alessandra Mandolesi ◽  
Khaled Mahmoud Abouelkhair ◽  
Cristian Loretelli ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Outcome ◽  
Cancer Patients ◽  
Genetic Profile ◽  
Wild Type ◽  
Third Line ◽  
Exon 20 ◽  
Colorectal Cancer Patients ◽  
A Prospective Study ◽  
Selection Of

3591 Background: Translational research identified numerous putative markers for a “beyond-k-RAS” selection of colorectal cancer patients receiving cetuximab, but none of these entered clinical practice mainly because prospective validation is lacking. The aim of our study was to evaluate whether a panel of biomarkers, prospectively analysed may be able to predict patients’ clinical outcome more accurately than k-RAS status alone. Methods: Metastatic, K-RAS wild type colorectal cancer patients, candidate to receive second/third-line cetuximab with chemotherapy have been prospectively allocated, after informed consent, into 2 groups on the basis of their genetic profile: favourable (BRAF and PIK3CA exon 20 wild type, EGFR GCN ≥ 2.6, HER-3 Rajkumar score ≤ 8, IGF-1 immunostaining < 2) and unfavourable (any of the previous markers altered or mutated). All patients received cetuximab treatment as planned by treating physician who was unaware of biomarkers results. To detect a difference in terms of response rate (RR) among patients with an unfavourable profile (estimated around 25%) and patients with a favourable profile (estimated around 60%), assuming a probability alpha of 0.05 and beta of 0.05, required sample size will be 46 patients. Results: 31 patients have been enrolled, most patients (27, 86%) received cetuximab as third-line. Eleven patients (35%) were allocated to the favourable profile and 20 patients (75%) to the unfavourable profile. Patients with the unfavourable profile showed 1 BRAF mutation, 2 PIK3CA exon 20 mutations, 12 cases of EGFR GCN < 2.6, 13 cases of HER-3 and 11 cases of IGF-1 overexpression respectively. RR in the favourable and unfavourable group was 7/11 (64%) and 1/20 (5%) (p= 0.008) respectively. The favourable group also showed an improved median TTP (8 months vs. 2.6 months, p = 0.0007) and OS (16 months vs. 6 months, p = 0.0002). Conclusions: Our results suggest that prospective selection of candidates for cetuximab may be able to improve clinical outcome in patients with a favourable profile. This approach, if confirmed, may also allow an early switch to alternative treatment in patients with an unfavourable profile.

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