Value of mismatch repair deficiency for predicting complete pathologic response to preoperative chemoradiation in rectal carcinoma.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 639-639
Author(s):  
Samuel Aguiar ◽  
Paula Mendonca Taglietti ◽  
Maria D. Begnami ◽  
Celso Abdon Mello ◽  
Erika Maria Monteiro Santos ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Mismatch Repair ◽  
Locally Advanced ◽  
Pathologic Response ◽  
Preoperative Radiation ◽  
Complete Pathologic Response ◽  
Mismatch Repair Deficiency ◽  
Repair Deficiency ◽  
Mmr Deficiency ◽  
Low Rate

639 Background: The objective of this study is to investigate the value of mismatch repair deficiency (MMR) in rectal cancers as a predictive fator of response to chemoradiation in rectal cancer. Methods: We evaluated a consecutive cohort of 109 patients with locally advanced rectal carcinomas, treated with a total dose of 5,040 cGy of preoperative radiation therapy, concomitant with infusional 5-FU-based chemotherapy. Radical surgery (TME) was performed in all patients. MMR status was determined by imunohistochemistry in tumor tissue from biopsies prior to chemoradiation. The primary endpoint was complete pathologic response (pCR). Results: 63 patients (57.8%) were male, and the mean age was 60 years (range from 28 to 93). The rate of pCR was 18.3%. Among clinical variables (age, sex, distance to dentate line, per-treatment CEA level, and clinical assessment of response), only clinical complete response (cCR) was significant associated with cPR (p=0.009). Only two patients (1.8%) presented tumors with MMR deficiency. These 2 patients had cPR. Despite the very low rate of MMR deficiency, the association with cPR was significant (p=0.032). Conclusions: Considering the low rate of MMR deficiency found, we do not consider MMR status as a good tool for predicting pathologic response to chemoradiation in rectal cancer. Further investigation can be considered among the subgroup of Lynch syndrome patients.

scholarly journals DNA Mismatch Repair Deficiency in Rectal Cancer: Benchmarking Its Impact on Prognosis, Neoadjuvant Response Prediction, and Clinical Cancer Genetics

2016 ◽  
Vol 34 (25) ◽  
pp. 3039-3046 ◽  
Author(s):  
Nicole de Rosa ◽  
Miguel A. Rodriguez-Bigas ◽  
George J. Chang ◽  
Jula Veerapong ◽  
Ester Borras ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Mismatch Repair ◽  
Pathologic Response ◽  
Mismatch Repair Deficiency ◽  
Cancer Specific Survival ◽  
Dna Mismatch ◽  
Repair Deficiency ◽  
Rectal Cancers ◽  
Dna Mismatch Repair Deficiency

Purpose DNA mismatch repair deficiency (dMMR) hallmarks consensus molecular subtype 1 of colorectal cancer. It is being routinely tested, but little is known about dMMR rectal cancers. The efficacy of novel treatment strategies cannot be established without benchmarking the outcomes of dMMR rectal cancer with current therapy. We aimed to delineate the impact of dMMR on prognosis, the predicted response to fluoropyrimidine-based neoadjuvant therapy, and implications of germline alterations in the MMR genes in rectal cancer. Methods Between 1992 and 2012, 62 patients with dMMR rectal cancers underwent multimodality therapy. Oncologic treatment and outcomes as well as clinical genetics work-up were examined. Overall and rectal cancer–specific survival were calculated by the Kaplan-Meier method. Results The median age at diagnosis was 41 years. MMR deficiency was most commonly due to alterations in MSH2 (53%) or MSH6 (23%). After a median follow-up of 6.8 years, the 5-year rectal cancer–specific survival was 100% for stage I and II, 85.1% for stage III, and 60.0% for stage IV disease. Fluoropyrimidine-based neoadjuvant chemoradiation was associated with a complete pathologic response rate of 27.6%. The extent of surgical resection was influenced by synchronous colonic disease at presentation, tumor height, clinical stage, and pelvic radiation. An informed decision for a limited resection focusing on proctectomy did not compromise overall survival. Five of the 11 (45.5%) deaths during follow-up were due to extracolorectal malignancies. Conclusion dMMR rectal cancer had excellent prognosis and pathologic response with current multimodality therapy including an individualized surgical treatment plan. Identification of a dMMR rectal cancer should trigger germline testing, followed by lifelong surveillance for both colorectal and extracolorectal malignancies. We herein provide genotype-specific outcome benchmarks for comparison with novel interventions.

scholarly journals 1758O Neoadjuvant pembrolizumab in localized/locally advanced solid tumors with mismatch repair deficiency

2021 ◽  
Vol 32 ◽  
pp. S1210
Author(s):  
K. Ludford ◽  
K. Raghav ◽  
M.A. Blum Murphy ◽  
N.D. Fleming ◽  
D. Nelson ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Solid Tumors ◽  
Locally Advanced ◽  
Advanced Solid Tumors ◽  
Mismatch Repair Deficiency ◽  
Repair Deficiency

Total Neoadjuvant Treatment for Rectal Cancer: Preliminary Experience

2020 ◽  
pp. 000313482095149
Author(s):  
Hayim Gilshtein ◽  
Amandeep Ghuman ◽  
Mirelle Dawoud ◽  
Shlomo Yellinek ◽  
Ilan Kent ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Pathologic Response ◽  
Pathological Response ◽  
Complete Pathologic Response ◽  
Regression Analyses ◽  
Complete Pathological Response

Introduction: Administration of chemotherapeutic regimens such as FOLFOX or CAPEOX with chemoradiation in the neoadjuvant setting, termed total neoadjuvant treatment (TNT), was introduced in recent years. By increasing the complete pathologic and clinical responses, patients with locally advanced rectal cancer may have better oncologic outcomes and potentially abstain from undergoing a proctectomy. Methods: All patients who underwent TNT at a single National Accreditation Program for Rectal Cancer accredited referral center were included. A retrospective analysis was performed using a computerized Institutional Review Board-approved database. Patient demographics, diagnostic workup, treatment regimens, and surgical and pathological reports were reviewed. Complete pathological response was the primary outcome. Univariable and multivariable logistic regression analyses were performed to identify potential factors predisposing to complete pathological response. Results: Thirty patients met the inclusion criteria, 14(46.6%) of whom had complete pathologic response. There was no difference in baseline demographic characteristics between patients who achieved complete pathological response and those who did not. Pathology revealed a 92% intact mesorectum rate in the complete pathologic response group and a mean of 24 harvested lymph nodes in the entire study cohort. Both univariable and multivariable logistic regression analyses failed to demonstrate statistically significant factors predicting complete pathologic response, magnetic resonance imaging (MRI) tumor size, and posttreatment MRI lymph node positivity. Conclusion: TNT is safe and efficient for patients with locally advanced rectal cancer. It increases complete pathological and clinical response rates and may more widely evolve to be the treatment of choice in this group of patients in the near future.

scholarly journals Intensive surveillance endoscopy for multiple gastrointestinal tumors in a patient with constitutional mismatch repair deficiency: case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Takayuki Ando ◽  
Takahiko Nakajima ◽  
Rei Fukuda ◽  
Keiko Nomura ◽  
Yo Niida ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Mismatch Repair ◽  
Mismatch Repair Deficiency ◽  
Aggressive Approach ◽  
Repair Deficiency ◽  
Partial Colectomy ◽  
Surveillance Endoscopy ◽  
Constitutional Mismatch Repair Deficiency ◽  
Intensive Surveillance

Abstract Background Constitutional mismatch repair deficiency (CMMRD) is an extremely rare autosomal recessive hereditary disease characterized by the absence of mismatch repair gene activity from birth, which results in brain tumors, colonic polyposis, gastrointestinal cancers, and lymphomas later in life. An aggressive approach, including colectomy or proctocolectomy, is recommended for the treatment of colorectal cancer. Additionally, partial colectomy with subsequent endoscopic surveillance may be an alternative strategy due to poor patient’s condition, although there is no evidence of surveillance endoscopy after partial colectomy for CMMRD. Case presentation A 13-year-old male patient with a history of T-lymphoblastic lymphoma underwent total gastrointestinal endoscopy, which revealed rectal cancer, colorectal polyposis, and duodenal adenoma. Differential diagnosis included constitutional mismatch repair deficiency according to its scoring system and microsatellite instability, and subsequent germline mutation testing for mismatch repair genes confirmed the diagnosis of constitutional mismatch repair deficiency based on a homozygous mutation in mutS homolog 6 (MSH6). The patient and his family refused colectomy due to the high risk of malignancies other than colorectal cancer, which could require radical surgery. Therefore, the patient underwent low anterior resection of the rectosigmoid colon for rectal cancer and intensive surveillance endoscopy for the remaining colon polyposis. During the 3-year period after initial surgery, 130 polyps were removed and the number of polyps gradually decreased during 6-months interval surveillance endoscopies, although only one polyp was diagnosed as invasive adenocarcinoma (pT1). Conclusions Our experience of short surveillance endoscopy illustrates that this strategy might be one of options according to patient’s condition.

Rates of pathologic complete response and sphincter-sparing surgery after neoadjuvant radiochemotherapy with or without regional pelvic hyperthermia for locally advanced rectal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 622-622
Author(s):  
Cihan Gani ◽  
Christopher Schroeder ◽  
Ulf Lamprecht ◽  
Michael Bamberg ◽  
Bernhard Berger
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Pathologic Response ◽  
Neoadjuvant Radiochemotherapy ◽  
Complete Pathologic Response ◽  
Regional Hyperthermia ◽  
Significant Difference ◽  
The Impact

622 Background: Regional pelvic hyperthermia is frequently added to neoadjuvant radiochemotherapy for locally advanced rectal cancer. The present retrospective study is the first to evaluate the impact of hyperthermia on rates of complete pathologic response and sphincter-sparing surgery in the context of a standard up-to-date neoadjuvant radiochemotherapy scheme. Methods: Between 2007 and 2010, 85 consecutive patients with locally advanced cancer (cT3, cT4, cN+) of the middle and lower rectum received neoadjuvant radiochemotherapy at our institution. 45 of 85 patients (“RCT group”) received standard treatment consisting of radiotherapy to the pelvis with 5040 cGy in 28 fractions of 180 cGy and 5-fluorouracil as a continuous infusion with 1000 mg/m² over 120 hours during the first and fifth week of treatment. 40 of 85 patients (“HRCT group”) received the same treatment with at least four treatments of weekly regional hyperthermia. Target temperature was 40.5°C for at least 60 minutes. Total mesorectal excision was routinely performed. Results: No significant difference in the distribution of age, gender, clinical stage and tumor grade was observed between both groups. Complete pathologic response was seen in 6.7% of patients in the RCT group and 22% of patients in the HRCT group (p=0.034). Overall rates of sphincter-sparing surgery were 64% in the RCT group and 65% in HRCT. However for deep seated tumors located within 4 cm of the anal verge (based on initial staging), sphincter sparing surgery was achieved in only 11.1% of patients in the RCT group but 35.7% of patients in the HRCT group (p = 0.19). Conclusions: The addition of regional hyperthermia to neoadjuvant radiochemotherapy significantly increases the rate of complete pathologic response, with a tendency towards higher rates of sphincter-sparing surgery for deep seated tumors.

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