Molecular markers as predictors of tumor response to preoperative chemoradiotherapy in locally advanced rectal adenocarcinoma

2004 ◽  
Vol 11 (S2) ◽  
pp. S117-S117
Author(s):  
S. E. Rodriguez-Ramirez ◽  
I. Alvarado ◽  
S. Labastida ◽  
P. Luna
Keyword(s):  
Molecular Markers ◽  
Tumor Response ◽  
Locally Advanced ◽  
Rectal Adenocarcinoma ◽  
Preoperative Chemoradiotherapy

Gene and MicroRNA Expression Are Predictive of Tumor Response in Rectal Adenocarcinoma Patients Treated With Preoperative Chemoradiotherapy

2016 ◽  
Vol 232 (2) ◽  
pp. 426-435 ◽  
Author(s):  
Caterina Millino ◽  
Isacco Maretto ◽  
Beniamina Pacchioni ◽  
Maura Digito ◽  
Antonino De Paoli ◽  
...  
Keyword(s):  
Tumor Response ◽  
Rectal Adenocarcinoma ◽  
Preoperative Chemoradiotherapy ◽  
Microrna Expression

Evidence for improved pathologic complete response (PCR) rate after preoperative chemoradiotherapy with 5-FU/oxaliplatin (5FU/OX) for rectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3567-3567 ◽  
Author(s):  
C. M. Dolinsky ◽  
N. N. Mahmoud ◽  
R. Mick ◽  
W. Sun ◽  
R. W. Whittington ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Retrospective Study ◽  
Residual Disease ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Rectal Adenocarcinoma ◽  
Preoperative Chemoradiotherapy ◽  
Malignant Cells ◽  
Long Term Outcomes

3567 Background: The use of preoperative chemoradiotherapy (chemo/RT) with 5-FU for locally advanced rectal cancer has increased dramatically. The addition of oxaliplatin (OX) to preoperative 5-FU may be a more active regimen than 5-FU alone. This retrospective study was undertaken to describe clinical outcomes in patients (pts) with rectal cancer treated with 5FU/OX or 5-FU alone. Methods: Between 11/90 and 4/05, 114 pts with rectal adenocarcinoma underwent preoperative chemo/RT at the University of Pennsylvania. Chemotherapy consisted of 5FU/OX in 36 (32%) pts and 78 (68%) pts received 5-FU. All pts received preoperative RT (median dose 5040 cGy). The two groups were balanced in terms of demographic and tumor related factors including tumor size, stage and distance from the anal verge. Median follow-up from preoperative chemo/RT was 24 months (range 2–125 months). A total of 105 (92%) pts had surgical resections; 61 (58%) with LAR, 44 (42%) with APR. PCR was defined as either no evidence of viable malignant cells in specimen or scattered, isolated malignant cells without gross residual disease. Non-surgical pts were counted as treatment failures. Results: The PCR rate was 36.1% (95% CI 20.4–51.8%) in 5FU/OX pts and 12.8% (95% CI 5.4–20.2%) in 5-FU pts. The probability of observing 13 PCRs in 36 5FU/OX pts if the actual PCR rate was 15% is equal to 0.001. Rates of any grade III/IV toxicity were similar between each regimen (20% 5FU/OX vs. 17% 5FU). Long term outcomes (2yr rate±SE) of local control, freedom from distant failure and progression-free survival in 23 pts who achieved a PCR were: 100%, 94%±6% and 94%±6%, respectively. In 85 pts with gross residual disease, these rates were: 87%±5, 77%±5% and 71%±6%, respectively. Conclusion: In this retrospective study, patients receiving 5FU/OX with radiation had a higher rate of PCR than those receiving 5FU alone. Overall, a PCR may lead to improved long-term outcomes. A prospective randomized trial to test superiority of the 5FU/OX regimen is warranted. [Table: see text]

Randomized phase II trial of preoperative chemoradiotherapy with or without cetuximab in locally advanced rectal adenocarcinoma.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 537-537 ◽  
Author(s):  
A. David McCollum ◽  
Darren M. Kocs ◽  
Punit Chadha ◽  
Michael A. Monticelli ◽  
Thomas E. Boyd ◽  
...  
Keyword(s):  
Local Recurrence ◽  
Locally Advanced ◽  
Rectal Adenocarcinoma ◽  
Advanced Rectal Cancer ◽  
Preoperative Chemoradiotherapy ◽  
Locally Advanced Rectal Cancer ◽  
Preoperative Radiation ◽  
Pelvic Radiotherapy ◽  
Recurrence Rates ◽  
Grade 3

537 Background: Treatment for locally advanced rectal cancer (LARC) includes preoperative radiation concurrent with fluoropyrimidine chemotherapy (CRT). Local recurrence is a problem. Cetuximab is active in colorectal cancer and is effective with radiotherapy in other diseases. This study evaluated the pathologic response rate for LARC treated with preoperative chemoradiotherapy w/wo cetuximab. Methods: LARC (T3/4 or LN+, M0) pts were randomized to Arm1/Arm2. Arm 1 received standard pelvic radiotherapy (5040-5400cGy in daily fractions) with continuous infusional 5-FU (225mg/m2/day); Arm 2 received identical chemoradiotherapy + concurrent cetuximab (400mg/m2 initial dose) 1 week before pelvic radiotherapy, followed by 250mg/m2 weekly for the duration of chemoradiotherapy. After study treatment completion, pts were re-evaluated clinically and radiographically for clinical response. After 6-8 weeks, patients underwent surgical resection. The primary end point was pathologic CR (pCR), and secondary endpoints included ORR, RFS, OS, and local recurrence rates. Results: 139 pts were enrolled (Arm 1=69/Arm2=70); Arm1/Arm2 median age 61/55 yrs, and stage II and III 59%, 39%/40%, 60%. In 124 postsurgery pts, pCR occurred in 17 Arm 1 pts (28.3%, 95% CI 17.5-41.4) and 17 Arm 2 pts (26.6%, 95% CI 16.3-39.1); TRG postsurgery was similar between treatment arms (Table). Grade 3 and 4 toxicities were largely nonhematologic: diarrhea 16%/22%, rash 0%/12%, dehydration 5%/8%, mucositis 5%/6%. The 5-yr RFS for Arm1/Arm2 was 61%/65%, 5-yr OS was 66%/83%, local recurrence was 3%/4%. Conclusions: The addition of cetuximab to preoperative CRT for LARC was associated with increased but manageable toxicities. pCR rates were similar between treatment arms, as were survival statistics and local recurrence rates. No association was found between KRAS status and pCR. Clinical trial information: NCT00527111. [Table: see text]

Association of T-cell infiltration assessed in pretherapeutic biopsies (PTB) of patients with locally advanced rectal adenocarcinoma (LARC) with tumor response and relapse after chemoradiotherapy (CRT) and rectal surgery.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3599-3599 ◽  
Author(s):  
Marc Van Den Eynde ◽  
Carine El Sissy ◽  
Amos Kirilovsky ◽  
Florence Marliot ◽  
Nacilla Haicheur ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Response ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Tumor Resection ◽  
Rectal Adenocarcinoma ◽  
Rectal Surgery ◽  
Pathological Response ◽  
Cell Infiltration ◽  
T Cell Infiltration

3599 Background: Pre-operative CRT followed by total mesorectal excision (TME) is nowadays the standard of care for patient with LARC (cT3-T4N0 or cTxN+). Currently, pathologic complete response occurs in +/- 15% after CRT. Colorectal cancer T-cell infiltration is a strong prognostic factor for survival after primary tumor resection. Our aim was to determine whether T-cell infiltration in PTB could be predictive of tumor response and relapse after CRT + TME. Methods: Between 1999 and 2012, patients with LARC who underwent CRT + TME and with available clinical follow-up and PTB (with sufficient tumor cells density) were identified at the Cliniques universitaires St-Luc. The density of CD3 (T cells) and CD8 (cytotoxic) was quantified on immunostained PTB slides and analyzed with a dedicated image analysis software on whole-slide imaging. Comparisons were made using the Wilcoxon-Mann-Whitney test. Cumulative disease-free survival (DFS) was performed using the Kaplan-Meier estimator and compared by log-rank tests. Cox regression we used for uni- and multi-variate analysis. P value of less than 0.05 was considered statistically significant. Results: 154 patients (sex ratio M/F 1.8; mean age 65 years-old; upper (20%), mid (29%) and low rectum (51%), synchronous metastases (11%)) were analyzed. High CD3 and CD8 PTB densities were significantly associated with a higher pathological response (Dworak 3-4) and lower ypTNM stage after CRT +TME (p < 0,05). Higher CD3 and CD8 PTB densities were associated with higher patient DFS (CD3: HR = 2,30 (CI95%:1,15-4,59) p = 0,02; CD8: HR = 1,95 (CI95%: 1,01-3,75) p = 0,04). These results were confirmed in uni and multivariate analysis. CD3 and CD8 PTB densities added to pathological response (ypTNM/Dworak) but also clinical response (ycTNM) after CRT + TME increases significantly the accuracy prediction of tumor relapse. Conclusions: Pretherapeutic T-cell infiltration of LARC is predictive of tumor response and relapse after CRT +TME. This biomarker could be helpful for patient treatment decision. It must be validated in larger patient cohorts.

Specific c-K-ras Gene Mutations as a Tumor-Response Marker in Locally Advanced Rectal Cancer Treated With Preoperative Chemoradiotherapy

2000 ◽  
Vol 7 (10) ◽  
pp. 727-731 ◽  
Author(s):  
Pedro Luna-P�rez ◽  
Julia Segura ◽  
Isabel Alvarado ◽  
Sonia Labastida ◽  
H�ctor Santiago-Pay�n ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Response ◽  
Locally Advanced ◽  
Gene Mutations ◽  
Advanced Rectal Cancer ◽  
Preoperative Chemoradiotherapy ◽  
Locally Advanced Rectal Cancer ◽  
Ras Gene

Molecular Markers for Recurrence and Sensitivity to Preoperative Chemoradiotherapy in Locally Advanced Rectal Tumours

2014 ◽  
Vol 31 (4-5) ◽  
pp. 347-353
Author(s):  
Benoît Romain ◽  
Nicolas Meyer ◽  
Cécile Brigand ◽  
Marie-Pierre Chenard ◽  
Anne Schneider ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Locally Advanced ◽  
Preoperative Chemoradiotherapy
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