mRNA quantitation of thymidylate synthase and dihydropyrimidine dehydrogenase can predict disease-free survival in stage IIb and III colon and stage II and III rectal cancer

2001 ◽  
Vol 120 (5) ◽  
pp. A63-A63
Author(s):  
M KOMMANN ◽  
K LINK ◽  
W SCHWABE ◽  
P HAEUSSLER ◽  
J STRAETER ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Thymidylate Synthase ◽  
Dihydropyrimidine Dehydrogenase ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Free Survival ◽  
Mrna Quantitation ◽  
Disease Free

Multicenter phase II trial of neoadjuvant chemotherapy with mFOLFOX6 for stage II/III rectal cancer with a T3/T4 tumor FACT trial.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 713-713
Author(s):  
Toshiyuki Enomoto ◽  
Yoshihisa Saida ◽  
Kazuhiro Takabayashi ◽  
Jiro Nagao ◽  
Junichi Koike ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Postoperative Complications ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Response Rate ◽  
Disease Free Survival ◽  
Stage Ii ◽  
R0 Resection ◽  
Free Survival ◽  
Disease Free

713 Background: The efficacy and safety of neoadjuvant chemotherapy with mFOLFOX6 for stage II/III rectal cancer patients with a T3/T4 tumor is still unknown. Methods: Inclusion criteriain this study are as follows: Stage II/III (Ra/Rb) rectal cancer patients with a T3/T4 tumor. The primary endpoint is preoperative response rate, and the secondary endpoints are histological effect, R0 resection rate, pCR rate, down-staging rate, neoadjuvant therapy completion rate, toxicity, the incidence of postoperative complications, and 3-year disease-free survival. Computed tomography was performed after 4 courses of mFOLFOX6. Patients with disease progression (DP) underwent resection of the primary lesion, while those without DP received another 2 courses of treatment. Treatment was discontinued when resection was not possible in patients with DP. Results: Registered patients totaled 53 with a mean age of 60 (38–77). The number of patients with T3 and T4 tumors was 42 and 10, and patients at stages II and III were 10 and 42, respectively. One patient withdrew due to consent retraction. Median relative dose intensity of mFOLFOX6 therapy was 93.2% for L-OHP, 5-FU, and l-LV. Treatment completion was achieved in 96.2% and 84.6% for 4 and 6 courses, respectively, and withdrawal was due to patient’s discretion, not adverse events. Preoperative response rate was 51%. Surgery was performed in 78.8% of patients. Serious (grade ≥3) toxicity included neutropenia (n=5), leukopenia (n=1), thrombocytopenia (n=1), febrile neutropenia (n=1), nausea (n=1), vomiting (n=1), and peripheral neuropathy (n=2). The rates of R0 resection, pCR, and sphincter preservation were 91.0%, 10.3%, and 82.9%. The down staging rate was calculated as 2%. The median follow-up after surgery was 18.0 months. Median DFS was 17.3 months, and 1-year disease-free survival was 78.8%. Median OS was 22.0 months, and 1-year overall survival was 95.7%. Postoperative complications included suture failure (n=3), wound infection (n=2), pneumonia (n=1), and intestinal obstruction (n=1). Conclusions: Neoadjuvant chemotherapy using mFOLFOX6 is a safe and efficacious treatment option for rectal cancer, especially locally advanced disease. Clinical trial information: UMIN000006583.

scholarly journals Systematic Review: Adjuvant Chemotherapy for Locally Advanced Rectal Cancer with respect to Stage of Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-10
Author(s):  
Shahab Hajibandeh ◽  
Shahin Hajibandeh
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Stage Ii ◽  
Stage Iii ◽  
Free Survival ◽  
Disease Free

Background. Recent meta-analysis of 21 randomised controlled trials (RCTs) supports the use of adjuvant chemotherapy for nonmetastatic rectal carcinoma. In order to define a subgroup of patients who can potentially benefit from postoperative adjuvant chemotherapy, this study aims to review trials investigating adjuvant chemotherapy with respect to stage of disease in patients with locally advanced rectal cancer who had undergone surgery for cure (stage II and stage III). Methods. We searched electronic information sources to identify randomised trials evaluating adjuvant chemotherapy in patients with stages II and III rectal cancer with overall survival or disease-free survival as outcomes. Scottish Intercollegiate Guidelines Network notes on methodology were used to assess the methodological quality of the selected studies. Random-effects models were applied to calculate pooled outcome data. Results. Eight studies reporting total of 5527 patients were selected for analysis. Adjuvant chemotherapy was associated with statistically significant improvement in disease-free survival and overall survival compared to surgery alone in both stage II and stage III cancer. Conclusions. This study indicates that both stage II and stage III rectal cancer patients may benefit from postoperative adjuvant chemotherapy. However, the benefits of adjuvant chemotherapy for patients who already had neoadjuvant chemoradiation still remain unknown.

scholarly journals Addition of Platinum Derivatives to Fluoropyrimidine-Based Neoadjuvant Chemoradiotherapy for Stage II/III Rectal Cancer: Systematic Review and Meta-Analysis

2019 ◽  
Vol 111 (9) ◽  
pp. 887-902 ◽  
Author(s):  
Felix J Hüttner ◽  
Pascal Probst ◽  
Eva Kalkum ◽  
Matthes Hackbusch ◽  
Katrin Jensen ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Pathological Complete Response ◽  
Meta Analysis ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Complete Response ◽  
Distant Recurrence ◽  
Stage Ii ◽  
Free Survival ◽  
Disease Free

Abstract Background Current guidelines recommend neoadjuvant therapy for patients with stage II or III rectal cancer. The addition of platinum derivatives to fluoropyrimidine-based chemoradiotherapy has been frequently investigated, but their role in this setting remains controversial. Methods PubMed, Cochrane Library, and Web of Science were systematically searched for randomized trials comparing chemoradiotherapy with or without platinum agents in stage II or III rectal cancer. Main outcome parameters were overall and disease-free survival, additional outcomes included pathological complete response, isolated local recurrence, distant recurrence, toxicity, and perioperative morbidity. Time-to-event data were pooled as hazard ratios (HRs) by the inverse variance method and binary outcomes as odds ratios (ORs) by the Peto method with their respective 95% confidence interval (CI). All statistical tests were two-sided. Results Ten randomized controlled trials with data on 5599 patients were included in the meta-analysis. Platinum derivatives did not statistically significantly improve overall survival (HR = 0.93, 95% CI = 0.82 to 1.05, P = .23), disease-free survival (HR = 0.91, 95% CI = 0.83 to 1.01, P = .07), or local recurrence (OR = 0.83, 95% CI = 0.66 to 1.05, P = .12). However, it led to a statistically significant increase of pathological complete response (OR = 1.31, 95% CI = 1.10 to 1.55, P = .002) and a statistically significant reduction of distant recurrence (OR = 0.78, 95% CI = 0.66 to 0.92, P = .004). Benefits were accompanied by higher rates of grade 3 or 4 toxicities. Conclusions Intensified neoadjuvant chemoradiotherapy with the addition of platinum derivatives cannot be recommended routinely because it did not improve overall or disease-free survival and was associated with increased toxicity. It needs to be elucidated whether the benefits in distant recurrence and pathological complete response may be advantageous for selected high-risk patients.

The role of thymidylate synthase expression in prognosis and outcome of adjuvant chemotherapy in patients with rectal cancer.

1994 ◽  
Vol 12 (12) ◽  
pp. 2640-2647 ◽  
Author(s):  
P G Johnston ◽  
E R Fisher ◽  
H E Rockette ◽  
B Fisher ◽  
N Wolmark ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Thymidylate Synthase ◽  
Disease Free Survival ◽  
Free Survival ◽  
Primary Rectal Cancer ◽  
Bowel Project ◽  
Rectal Cancers ◽  
Prognostic Importance ◽  
Disease Free

PURPOSE We assessed the prognostic importance of the level of thymidylate synthase (TS) expression in patients with primary rectal cancer and whether, for Dukes' B and C cancer patients, the benefit of chemotherapy was associated with TS expression. PATIENTS AND METHODS The level of TS expression in the primary rectal cancers of 294 of 801 patients enrolled on protocol R-01 of the National Surgical Adjuvant Breast and Bowel Project (NSABP) was immunohistochemically assessed with the monoclonal antibody TS 106. RESULTS Forty-nine percent of patients whose tumors had low TS levels (n = 91) were disease free at 5 years compared with 27% of patients with high levels of TS (n = 203; P < .01). Moreover, 60% of patients with low TS levels were alive after 5 years compared with 40% of patients with high TS levels (P < .01). The level of TS protein was significantly associated with Dukes' stage (P < .01); patients with a more advanced Dukes' stage had a significantly higher level of TS. The level of TS expression remained prognostic for both disease-free survival (P < .01) and survival (P < .05) independent of Dukes' stage and other pathologic characteristics evaluated. Thirty-eight percent and 54% of patients with high TS levels (n = 71) were disease free and alive, respectively, after 5 years when treated with chemotherapy, compared with 17% and 31%, respectively, of similar patients when treated with surgery alone (n = 64) (P < .01). No difference was noted in disease-free survival (P = .46) or survival (P = .43) in patients with low TS levels. CONCLUSION The expression of TS is an important independent prognosticator of disease-free survival and survival in patients with rectal cancer. Adjuvant fluorouracil (5-FU)-based chemotherapy demonstrated significant improvement in disease-free and overall survival for patients with high TS levels. Prospective studies measuring TS levels will be needed to understand further the role of TS as a prognosticator of survival and chemotherapeutic benefit.

scholarly journals Disease-free Survival and Local Recurrence for Laparoscopic Resection Compared With Open Resection of Stage II to III Rectal Cancer

2019 ◽  
Vol 269 (4) ◽  
pp. 589-595 ◽  
Author(s):  
James Fleshman ◽  
Megan E. Branda ◽  
Daniel J. Sargent ◽  
Anne Marie Boller ◽  
Virgilio V. George ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Local Recurrence ◽  
Laparoscopic Resection ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Open Resection ◽  
Free Survival ◽  
Disease Free

Polymorphisms of the Repeated Sequences in the Enhancer Region of the Thymidylate Synthase Gene Promoter May Predict Downstaging After Preoperative Chemoradiation in Rectal Cancer

2001 ◽  
Vol 19 (6) ◽  
pp. 1779-1786 ◽  
Author(s):  
Elena Villafranca ◽  
Yury Okruzhnov ◽  
Miguel A. Dominguez ◽  
Jesús García-Foncillas ◽  
Ignacio Azinovic ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Thymidylate Synthase ◽  
Gene Promoter ◽  
Disease Free Survival ◽  
Lower Probability ◽  
Surgical Specimen ◽  
Free Survival ◽  
Tumor Downstaging ◽  
Ts Polymorphism ◽  
Disease Free

PURPOSE: Thymidylate synthase (TS) is an important target enzyme for the fluoropyrimidines. TS gene promoter possesses regulatory tandemly repeated (TR) sequences that are polymorphic in humans, depending on ethnic factors. These polymorphisms have been reported to influence TS expression. TS expression levels affect tumor downstaging after preoperative fluoruracil (5-FU)–based chemoradiation. Tumor downstaging correlates with improved local control and disease-free survival. The aim of this study is to correlate TR polymorphisms with downstaging and disease-free survival. PATIENTS AND METHODS: Sixty-five patients with rectal cancer underwent tumor resection after preoperative 5-FU–based chemoradiation. Tumor downstaging was evaluated by comparing the pretreatment T stage with the pathologic stage observed in the surgical specimen. TS polymorphism genotype was determined by polymerase chain reaction amplification of the corresponding TS promoter region, and products of amplification were electrophoresed, obtaining products of 220 bp (2/2), 248 bp (3/3), or both (2/3). The TS polymorphism genotype results were subsequently compared with the downstaging observed and with disease-free survival. RESULTS: Patients who were homozygous for triple TR (3/3) had a lower probability of downstaging than patients who were homozygous with double TR or heterozygous patients (2/2 and 2/3): 22% versus 60% (P = .036; logistic regression). Furthermore, a trend toward improved 3-year disease-free survival was detected in the 2/2 and 2/3 groups, compared with that in the 3/3 group (81% v 41%; P = .17). CONCLUSION: This preliminary study suggests that TS repetitive-sequence polymorphisms are predictive for tumor downstaging. TR sequences in TS promoter may be useful as a novel means of predicting response to preoperative 5-FU–based chemoradiation.

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