Genetic Polymorphisms in Genes Related to Oxidative Stress (GSTP1, GSTM1, GSTT1, CAT, MnSOD, MPO, eNOS) and Survival of Rectal Cancer Patients after Radiotherapy

Radiotherapy exerts part of its antineoplastic effect by generating oxidative stress, therefore genetic variation in oxidative stress-related enzymes may influence survival of rectal cancer patients. We hypothesized that genetic polymorphisms associated with higher amounts of reactive oxygen species (ROS) that exaggerate cytotoxic activity could improve survival after radiotherapy. We followed 114 rectal cancer patients who received radiotherapy for an average of 42.5 months. Associations between genotypes (GSTP1,GSTM1,GSTT1,CAT,MnSOD,MPOandeNOS) and overall survival were assessed using Kaplan-Meier curves and Cox proportional hazards regression. As hypothesized, patients carrying low ROS producingeNOSGlu298Asp asparagine allele showed an increased hazard of death compared to homozygous carriers of the glutamine allele (hazard ratio (HR): 2.10, 95% confidence interval (CI): 1.01–4.38). However, carriers of low ROS producingMPOG463A A allele had a decreased hazard of death compared to patients homozygous for the G allele (HR: 0.44, 95% CI: 0.21–0.93) although patients homozygous for the A allele had a slightly increased hazard (HR: 1.12, 95% CI: 0.25–5.08). This explorative study provides first results and highlights the need for further, larger studies to investigate association between genetic variation in oxidative stress genes and survival of rectal cancer patients who received radiotherapy.

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Improved survival by Helicobacter pylori-modulated immunity in gastric cancer patients with S-1 adjuvant chemotherapy

10.1101/2021.09.24.21263620 ◽

2021 ◽

Author(s):

Yuka Koizumi ◽

Sheny Ahmad ◽

Miyuki Ikeda ◽

Akiko Yashima-Abo ◽

Ginny Espina ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Advanced Gastric Cancer ◽

Cancer Patients ◽

Proportional Hazards ◽

Immune Escape ◽

Cox Proportional Hazards ◽

Prolonged Survival ◽

Host Immune System ◽

Gastric Cancer Patients

Background: Paradoxically, Helicobacter pylori-positive (HP+) advanced gastric cancer patients have a better prognosis than those who are HP-negative (HP-). Immunologic and statistical analyses can be used to verify whether systematic mechanisms modulated by HP are involved in this more favorable outcome. Methods: A total of 658 advanced gastric cancer patients who underwent gastrectomy were enrolled. HP infection, mismatch repair, programmed death-ligand 1 (PD-L1), and CD4/CD8 proteins, and microsatellite instability were analyzed. Overall survival (OS) and relapse free survival (RFS) rates were analyzed after stratifying clinicopathological factors. Cox proportional hazards regression analysis was performed to identify independent prognostic factors. Results: Among 491 cases that were analyzed, 175 (36%) and 316 (64%) cases were HP+ and HP⁻, respectively. Analysis of RFS indicated an interaction of HP status among the subgroups for S-1 Dose (P=0.0487) and PD-L1 (P=0.016). HP+ patients in the PD-L1- group had significantly higher five-year OS and RFS than HP- patients (81% vs. 68%; P=0.0011; HR 0.477; and 76% vs. 63%; P=0.0011; HR 0.508, respectively). The five-year OS and RFS was also significantly higher for HP⁺ compared to HP- patients in the PD-L1-/S-1-reduced group (86% vs. 46%; p=0.0014; HR 0.205; 83% vs. 34%; p=0.001; HR 0.190, respectively). Thus, HP status was identified as one of the most potentially important independent factors to predict prolonged survival. Conclusion: Modulation of host immune system function by HP may contribute to prolonged survival in the absence of immune escape mechanisms of gastric cancer.

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Prognostic Value of Multiparametric MRI-Based Radiomics model: Potential Role for Chemotherapeutic Benefits in Locally Advanced Rectal Cancer

10.21203/rs.3.rs-44982/v1 ◽

2020 ◽

Author(s):

Yanfen Cui ◽

Wenhui Yang ◽

Jialiang Ren ◽

Dandan Li ◽

Xiaosong Du ◽

...

Keyword(s):

Rectal Cancer ◽

Proportional Hazards ◽

Risk Group ◽

Locally Advanced ◽

Disease Free Survival ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Cox Proportional Hazards ◽

Low Risk ◽

Radiomics Signature

Abstract Background: Distant metastasis is the major cause of treatment failure in locally advanced rectal cancer (LARC). Adjuvant chemotherapy (AC) is usually used for distant control. However, only certain subgroups of patients could benefit from AC. Our aim was to develop a radiomics model for the prediction of survival and chemotherapeutic benefits using pretreatment multiparameter MR images and clinicopathological features in patients with LARC. Methods: 186 consecutive patients with LARC underwent feature extraction from the whole tumor on T2-weighted (T2w), contrast enhanced T1-weighted (cT1w), and ADC images. Feature selection was based on feature stability and the Boruta algorithm. Radiomics signatures for predicting DFS (disease-free survival) were then generated using the selected features. Combining clinical risk factors, a radiomics nomogram was constructed using Cox proportional hazards regression model. The predictive performance was evaluated by Harrell's concordance indices (C-index) and time-independent receiver operating characteristic (ROC) analysis. Results: Four features were selected to construct the radiomics signature, which was significantly associated with DFS (P < 0.001). The radiomics nomogram, incorporating radiomics signature and two clinicopathological variables (pN and tumor differentiation), exhibited better prediction performance for DFS than the clinicopathological model, with C-index of 0.780 (95%CI, 0.718-0.843) and 0.803 (95%CI, 0.717-0.889) in the training and validation cohorts, respectively. The radiomics nomogram-defined high-risk group had a shorter DFS, DMFS, and OS than those in the low-risk group (all P <0.05). Further analysis showed that patients with higher nomogram-defined score exhibited a favorable response to AC while the low-risk could not. Conclusion: This study demonstrated that the newly developed pretreatment multiparameter MRI-based radiomics model could serve as a powerful predictor of prognosis, and may act as a potential indicator for guiding AC in patients with LARC.

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Serum Lipids and the Risk of Gastrointestinal Malignancies in the Swedish AMORIS Study

Journal of Cancer Epidemiology ◽

10.1155/2012/792034 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 30

Author(s):

Wahyu Wulaningsih ◽

Hans Garmo ◽

Lars Holmberg ◽

Niklas Hammar ◽

Ingmar Jungner ◽

...

Keyword(s):

Rectal Cancer ◽

Colon Cancer ◽

Cancer Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Gastrointestinal Malignancies ◽

Colon Cancer Risk ◽

Colon And Rectal Cancer ◽

Increased Risk ◽

Lipid Components

Background. Metabolic syndrome has been linked to an increased cancer risk, but the role of dyslipidaemia in gastrointestinal malignancies is unclear. We aimed to assess the risk of oesophageal, stomach, colon, and rectal cancers using serum levels of lipid components.Methods. From the Swedish Apolipoprotein Mortality Risk (AMORIS) study, we selected 540,309 participants (> 20 years old) with baseline measurements of total cholesterol (TC), triglycerides (TG), and glucose of whom 84,774 had baseline LDL cholesterol (LDL), HDL cholesterol (HDL), apolipoprotein B (apoB), and apolipoprotein A-I (apoA-I). Multivariate Cox proportional hazards regression was used to assess glucose and lipid components in relation to oesophageal, stomach, colon, and rectal cancer risk.Results. An increased risk of oesophageal cancer was observed in persons with high TG (e.g. HR: 2.29 (95% CI: 1.42–3.68) for the 4th quartile compared to the 1st) and low LDL, LDL/HDL ratio, TC/HDL ratio, log (TG/HDL), and apoB/apoA-I ratio. High glucose and TG were linked with an increased colon cancer risk, while high TC levels were associated with an increased rectal cancer risk.Conclusion. The persistent link between TC and rectal cancer risk as well as between TG and oesophageal and colon cancer risk in normoglycaemic individuals may imply their substantiality in gastrointestinal carcinogenesis.

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Comorbidities and Myelodysplatic Syndromes.

Blood ◽

10.1182/blood.v114.22.2789.2789 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2789-2789 ◽

Cited By ~ 3

Author(s):

Kiran Naqvi ◽

Guillermo Garcia-Manero ◽

Sagar Sardesai ◽

Jeong Oh ◽

Sherry Pierce ◽

...

Keyword(s):

Cancer Patients ◽

Median Survival ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Hazards Model ◽

Kaplan Meier ◽

Comorbidity Scores ◽

Severe Comorbidity

Abstract Abstract 2789 Poster Board II-765 Background: Cancer patients often experience comorbidities that may affect their therapeutic options, prognosis, and outcome (1). Limited studies have evaluated the characteristics and impact of comorbidities in myelodysplastic syndromes (MDS). The aim of this study was to determine the effect of comorbidities on the survival of patients with MDS. Methods: We reviewed the medical records of 500 consecutive MDS patients who presented to MD Anderson Cancer Center from January 2002 to June 2004. The Adult Comorbidity Evaluation-27 (ACE-27), a validated 27-item comorbidity index for cancer patients (2), was used to assess the severity of comorbid conditions. For each patient, we obtained demographic data and specific staging information based on the International Prognostic Scoring System (IPSS). We also collected information on stem cell transplantation (SCT), mortality and survival. Kaplan-Meier methods and log-rank tests were used to assess survival. Multivariate analysis was performed using the Cox Proportional Hazards Model. Results: Of the 500 patients included in this study, 327 (65.4%) were male, and 436 (87.9%) were white; median age at presentation was 66.6 years (17.7, 93.5); mean duration of follow-up was 23.5 months (0, 88). A total of 49% of patients had IPSS intermediate-1 or lower risk. The ACE-27 comorbidity scores were as follows: none, 106 patients (21.2%); mild, 213 (42.6%); moderate, 108 (21.6%); and severe, 73 (14.6%). Three hundred and eighty one (76.2%) patients died, and 44 (8.8%) patients underwent SCT. Overall median survival using the Kaplan-Meier method was 17.6 months. Median survival according to ACE-27 scores was: 27.9 months for no comorbidity, 18.9 months for mild comorbidity, 15.2 months for moderate comorbidity, and 9.7 months for severe comorbidity. This trend reached statistical significance (p < 0.0001). The median survival by IPSS ranged from 40.9 months for patients in the low risk group versus 8.1 months for those in the high risk category (p < 0.0001). The hazards ratio obtained from the multivariate Cox Proportional Hazards Model was 1.5 and 2.0 for moderate and severe comorbidity scores when adjusted for age and IPSS (p < 0.0001). A linear trend was also observed between the severity of comorbidity and having received SCT (p = 0.001). Of the 44 patients who had SCT, 21 (47.7%) died. The median survival of patients who did not undergo stem cell transplantation ranged from 22.7 months for patients with no comorbidity to 9.3 months for patients with severe comorbidity (p = 0.0002). Conclusion: Comorbidities had a significant impact on the survival of patients with myelodysplastic syndrome. Patients with higher ACE-27 comorbidity scores had a shorter survival than those with no comorbidity, independent of their age and the IPSS risk group. Also patients with comorbid conditions received SCT less often than those without comorbidity. A comprehensive assessment of comorbidity is therefore needed to determine the prognosis in patients with MDS. References: (1) Extermann M. Measurement and impact of comorbidity in older cancer patients. Crit Rev Oncol Hematol. 2000;35:181-200. (1) Piccirillo JF, Tierney RM, Costas I, et al. Prognostic importance of comorbidity in a hospital-based cancer registry. JAMA. 2004;291:2441-47. Disclosures: No relevant conflicts of interest to declare.

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Impact of multidisciplinary bladder cancer care for muscle invasive bladder cancer: A propensity score matched analysis of survival outcomes.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.455 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 455-455 ◽

Cited By ~ 1

Author(s):

Girish S. Kulkarni ◽

Thomas Hermanns ◽

Kathy Li ◽

Yanliang Wei ◽

Bimal Bhindi ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Patients ◽

Proportional Hazards ◽

Treatment Options ◽

Cox Proportional Hazards ◽

Survival Outcomes ◽

Primary Therapy ◽

Bladder Preservation ◽

Trimodal Therapy ◽

Significant Difference

455 Background: We started in 2008 a Multidisciplinary Bladder Cancer Clinic (MDBCC), where complex bladder cancer patients are assessed concurrently by urologic and radiation oncologists, with support from medical oncologists. Patients have the opportunity to discuss various treatment options including radical cystectomy (RC) or bladder sparing trimodal therapy (TMT; endoscopic resection, radiotherapy and chemotherapy). Although reports have shown comparable outcomes of TMT to cystectomy, no direct comparison to RC has been published and no randomized studies are available. We report our long term outcomes of multidisciplinary care, comparing TMT to surgery using propensity-matched analyses. Methods: Patients seen in our MDBCC receiving TMT for MIBC from 2008 to 2012 were identified and matched, using propensity scores, to patients operated by RC. Matching occurred on age, ECOG status, Charlson comorbidity score, cT stage, cN stage and date of treatment. Overall survival (OS) and disease-specific survival (DSS) were assessed with Cox Proportional hazards modeling and competing risk analysis, respectively. Results: Between 2008 and 2012, 248 patients were assessed in the MDBCC. Of these, 162 (65%) had MIBC. Nearly half (80) opted for radiotherapy +/- concurrent cisplatin chemotherapy and 49 underwent full bladder preservation with TMT as their primary therapy. We matched 48 TMT patients with 48 RC patients with no imbalances. Median age of the cohort was 67.5 years with 29.2% cT3/cT4. With a median follow up time of 3.62 years, there were 19 (39.6%) deaths (7 from bladder cancer) in the RC group and 15 (31.3%) deaths (6 from bladder cancer) in the TMT group. 5 year DSS was 85.2% and 84.7% with TMT and surgery, respectively (p > 0.05). There was no statistically significant difference in DSS between the two groups (HR for TMT 1.31 (0.40-4.23), p = 0.66) or in OS (HR for TMT 0.77 (0.34-1.75), p = 0.53). Conclusions: Bladder cancer patients benefit from a multidisciplinary approach.. In selected patients with MIBC, chemo-radiation yields survival outcomes similar to matched RC patients. BC patients should be offered the possibility to discuss various treatment options.

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Clinical outcomes of pancreas cancer patients with peritoneal spread: Results from the chord consortium.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e19268 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e19268-e19268

Author(s):

Mehrnoosh Pauls ◽

Abdulaziz AlJassim AlShareef ◽

Winson Y. Cheung ◽

Rachel Anne Goodwin ◽

Brandon M. Meyers ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Patients ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Advanced Pancreatic Cancer ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

First Line ◽

The Impact ◽

Line Chemotherapy

e19268 Background: Prior studies have demonstrated that clonal cells that give rise to pancreatic peritoneal metastases (PM) are geographically and genetically distinct from clonal cells, giving rise to lung and liver metastases. The objective of this study was to assess if there is a distinct difference in prognosis and therapeutic response among patients with pancreatic cancer with (PM compared to the lung/liver. Methods: Using a retrospective cohort design, medical records from adult patients diagnosed with metastatic adenocarcinoma of the pancreas at five Canadian academic cancer centers (2014 - 2019) were reviewed. Prognostic variables including age, Charlson comorbidity index, ECOG, cigarette smoking, nodal status, sites of metastases, and first line chemotherapy were collected. Cox proportional hazards model (MVA) was used to examine the association between peritoneal involvement and survival, adjusted for measured confounders. Analyses were completed using SAS, where alpha of 0.05 was defined as the level of significance. Results: A total of 1161 patients were included. Metastatic sites included peritoneum (n = 170, 14.6%), lung (n = 145, 12.5%) and liver (n = 563, 48.5%). Patients with PM received first-line FOLFIRINOX (FFX, n = 31), Gemcitabine + nab-paclitaxel (G/N, n = 20), Gemcitabine (G, n = 18), and no treatment (n = 97). In univariate analyses, worse ECOG PS was associated with PM (p = 0.002). The majority of patients died (89%), with a median overall survival (OS) of 3 vs 7 months for patients with PM and those without PM (p < 0.001), respectively. The median OS in patient whom receive first-line chemotherapy was 7 months in FFX group (95% CI 1.66-12.33), 6 months in G/N (95% CI 4.54-7.45) and 2 months in G group (95% CI 1.42-2.57). Patients had significantly better OS when treated with FFX or G/N compared to G alone (p = 0.002). Time to treatment failure was significantly shorter among patient treated with G alone compare to patients treated with FFX and G/N (P < 0.005). Conclusions: In the setting of combination chemotherapy for advanced pancreatic cancer, patients with PM continue to have a poor prognosis. This may be due to the impact of PM on PS and the inability to administer palliative chemotherapy. For eligible patients, FFX or G/N results in a higher OS than G monotherapy.

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Chemotherapy and Cardiotoxicity in Older Breast Cancer Patients: A Population-Based Study

Journal of Clinical Oncology ◽

10.1200/jco.2005.02.5841 ◽

2005 ◽

Vol 23 (34) ◽

pp. 8597-8605 ◽

Cited By ~ 226

Author(s):

John J. Doyle ◽

Alfred I. Neugut ◽

Judith S. Jacobson ◽

Victor R. Grann ◽

Dawn L. Hershman

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Proportional Hazards ◽

Population Based ◽

Cox Proportional Hazards ◽

Stage I ◽

Breast Cancer Patients ◽

Primary Tumors ◽

Increased Risk

Purpose Adjuvant chemotherapy, especially with anthracyclines, is known to cause acute and chronic cardiotoxicity in breast cancer patients. We studied the cardiac effects of chemotherapy in a population-based sample of breast cancer patients aged ≥ 65 years with long-term follow-up. Patients and Methods In the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we analyzed treatments and outcomes among women ≥ 65 years of age who were diagnosed with stage I to III breast cancer from January 1, 1992 to December 31, 1999. Propensity scores were used to control for baseline heart disease (HD) and other known predictors of chemotherapy, and Cox proportional hazards models were used to estimate the risk of cardiomyopathy (CM), congestive heart failure (CHF), and HD after chemotherapy. Results Of 31,748 women with stage I to III breast cancer, 5,575 (18%) received chemotherapy. Chemotherapy was associated with younger age, fewer comorbidities, hormone receptor negativity, multiple primary tumors, and advanced disease. Patients who received chemotherapy were less likely than other patients to have pre-existing HD (45% v 55%, respectively; P < .001). The hazard ratios for CM, CHF, and HD for patients treated with doxorubicin (DOX) compared with patients who received no chemotherapy were 2.48 (95% CI, 2.10 to 2.93), 1.38 (95% CI, 1.25 to 1.52), and 1.35 (95% CI, 1.26 to 1.44), respectively. The relative risk of cardiotoxicity among patients who received DOX compared with untreated patients remained elevated 5 years after diagnosis. Conclusion When baseline HD was taken into account, chemotherapy, especially with anthracyclines, was associated with a substantially increased risk of CM. As the number of long-term survivors grows, identifying and minimizing the late effects of treatment will become increasingly important.

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The HOXB13:IL17BR Expression Index Is a Prognostic Factor in Early-Stage Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.06.6944 ◽

2006 ◽

Vol 24 (28) ◽

pp. 4611-4619 ◽

Cited By ~ 181

Author(s):

Xiao-Jun Ma ◽

Susan G. Hilsenbeck ◽

Wilson Wang ◽

Li Ding ◽

Dennis C. Sgroi ◽

...

Keyword(s):

Breast Cancer ◽

Prognostic Factor ◽

Clinical Outcome ◽

Cancer Patients ◽

Proportional Hazards ◽

Early Stage ◽

Cox Proportional Hazards ◽

Tamoxifen Treatment ◽

Breast Cancer Patients ◽

Node Negative

Purpose We previously identified three genes, HOXB13, IL17BR and CHDH, and the HOXB13:IL17BR ratio index in particular, that strongly predicted clinical outcome in breast cancer patients receiving tamoxifen monotherapy. Confirmation in larger independent patient cohorts was needed to fully validate their clinical utility. Patients and Methods Expression of HOXB13, IL17BR, CHDH, estrogen receptor (ER) and progesterone receptor (PR) were quantified by real-time polymerase chain reaction in 852 formalin-fixed, paraffin-embedded primary breast cancers from 566 untreated and 286 tamoxifen-treated breast cancer patients. Gene expression and clinical variables were analyzed for association with relapse-free survival (RFS) by Cox proportional hazards regression models. Results ER and PR mRNA measurements were in close agreement with immunohistochemistry. In the entire cohort, expression of HOXB13 was associated with shorter RFS (P = .008), and expression of IL17BR and CHDH was associated with longer RFS (P < .0001 for IL17BR and P = .0002 for CHDH). In ER+ patients, the HOXB13:IL17BR index predicted clinical outcome independently of treatment, but more strongly in node-negative patients. In multivariate analysis of the ER+ node-negative subgroup including age, PR status, tumor size, S phase fraction, and tamoxifen treatment, the two-gene index remained a significant predictor of RFS (hazard ratio = 3.9; 95% CI, 1.5 to 10.3; P = .007). Conclusion This tumor bank study demonstrated HOXB13:IL17BR index is a strong independent prognostic factor for ER+ node-negative patients irrespective of tamoxifen therapy.

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An Explorative Analysis of ABCG2/TOP-1 mRNA Expression as a Biomarker Test for FOLFIRI Treatment in Stage III Colon Cancer Patients: Results from Retrospective Analyses of the PETACC-3 Trial

Cancers ◽

10.3390/cancers12040977 ◽

2020 ◽

Vol 12 (4) ◽

pp. 977 ◽

Cited By ~ 3

Author(s):

Jan Stenvang ◽

Eva Budinská ◽

Eric van Cutsem ◽

Fred Bosman ◽

Vlad Popovici ◽

...

Keyword(s):

Colon Cancer ◽

Mrna Expression ◽

Cancer Patients ◽

Proportional Hazards ◽

Statistical Significance ◽

Predictive Biomarkers ◽

Cox Proportional Hazards ◽

Stage Iii ◽

End Points ◽

Stage Iii Colon Cancer

Biomarker-guided treatment for patients with colon cancer is needed. We tested ABCG2 and topoisomerase 1 (TOP1) mRNA expression as predictive biomarkers for irinotecan benefit in the PETACC-3 patient cohort. The present study included 580 patients with mRNA expression data from Stage III colon cancer samples from the PETACC-3 study, which randomized the patients to Fluorouracil/leucovorin (5FUL) +/− irinotecan. The primary end-points were recurrence free survival (RFS) and overall survival (OS). Patients were divided into one group with high ABCG2 expression (above median) and low TOP-1 expression (below 75 percentile) (“resistant”) (n = 216) and another group including all other combinations of these two genes (“sensitive”) (n = 364). The rationale for the cut-offs were based on the distribution of expression levels in the PETACC-3 Stage II set of patients, where ABCG2 was unimodal and TOP1 was bimodal with a high expression level mode in the top quarter of the patients. Cox proportional hazards regression was used to estimate the hazard ratios and the association between variables and end-points and log-rank tests to assess the statistical significance of differences in survival between groups. Kaplan-Meier estimates of the survival functions were used for visualization and estimation of survival rates at specific time points. Significant differences were found for both RFS (Hazard ratio (HR): 0.63 (0.44–0.92); p = 0.016) and OS (HR: 0.60 (0.39–0.93); p = 0.02) between the two biomarker groups when the patients received FOLFIRI (5FUL+irinotecan). Considering only the Microsatellite Stable (MSS) and Microsatellite Instability-Low (MSI-L) patients (n = 470), the differences were even more pronounced. In contrast, no significant differences were observed between the groups when patients received 5FUL alone. This study shows that the combination of ABCG2 and TOP1 gene expression significantly divided the Stage III colon cancer patients into two groups regarding benefit from adjuvant treatment with FOLFIRI but not 5FUL.

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Does up-front definitive surgical resection with delayed chemotherapy in patients with stage IV rectal cancer compromise overall survival?

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.586 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 586-586

Author(s):

Bindu V. Manyam ◽

Shlomo A. Koyfman ◽

Davendra Sohal ◽

Ismail Mallick ◽

Chandana A. Reddy ◽

...

Keyword(s):

Rectal Cancer ◽

Overall Survival ◽

Surgical Resection ◽

Proportional Hazards ◽

Performance Status ◽

Rectal Adenocarcinoma ◽

Stage Iv ◽

Cox Proportional Hazards ◽

Significant Difference ◽

Poorly Differentiated

586 Background: Definitive resection of the primary is frequently part of the management of patients (pts) with stage IV rectal cancer with good performance status and low volume of systemic metastases. It is unclear whether delaying systemic therapy for up front surgical management of the primary compromises overall survival (OS). Methods: Pts with metastatic rectal adenocarcinoma who received definitive surgical resection between 1998-2011 were identified in an IRB approved registry. The sequencing of CT and surgery, and the use of perioperative radiation therapy (RT), was at the discretion of treating physicians. Preoperative chemotherapy (Pre-CT) regimens included 5-fluorouracil (5-FU) +/- leukovorin (LV), capecitabine, 5-FU/LV/oxaliplatin +/- avastin, or 5-FU/LV/irinocetan. RT dose was typically 50.4 Gy. OS was measured from the date of diagnosis. Baseline variables were compared using the Chi-square and unpaired t-tests. OS was calculated using the Kaplan Meier method. Univariate (UVA) and multivariate analysis (MVA) were performed using Cox proportional hazards regression to identify variables associated with OS. Results: In this study of 115 pts, 75 (65%) were treated with pre-CT, while 40 (35%) were treated with up front surgery. Of the pts who received surgery up front, 3 (8%) received RT and of the pts who received pre-CT, 62 (83%) received RT. The cohort was predominantly male (70%) with a median age of 57, median KPS of 80, and median follow-up of 24.1 months. 94% of pts had T3/T4 tumors, 80% had N+ disease, and 33% had poorly differentiated tumors. Liver directed therapy (LDT) was performed in 61% of pts. There was no significant difference in OS (32.3 vs. 32 months; p = 0.24) between pts treated with pre-CT and those who received surgery up front, respectively. UVA demonstrated that pre-CT was not associated with OS (HR 1.26; p = 0.544). MVA demonstrated that pts with poorly differentiated tumors (HR 2.04; p = 0.007) and those that did not undergo LDT (HR 2.45; p = 0.001) had inferior survival. Conclusions: Delaying systemic chemotherapy in order to achieve local control with surgical resection up front does not appear to impact OS in pts with stage IV rectal cancer.

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