Survival after adjuvant 5-FU treatment for stage III colon cancer: Possible role of mismatch repair (MMR) gene defect

562 Background: Current staging of patients (pts) with pathological stage III colon cancer is suboptimal; many pts still recur despite unremarkable preoperative staging work-up. We previously reported that early postoperative PET-CT can alter the stage and management of pts with high risk stage III colon cancer in up to 19% of patients. The aim of the current study was to expand the previous one to a larger cohort and to determine the role of early postoperative PET-CT in the general population of stage III colon cancer pts, regardless of their individual risk. Methods: A retrospective chart review of all consecutive pts with stage III colon cancer who underwent early postoperative PET-CT between 2007 and 2016. Demographic and clinicopathological data were collected. Results: 247 pts, 124 (50%) males, with a median age of 66 years (range, 30-92), were included. Pathological stage was IIIA, IIIB and IIIC in 18 (7.3%), 161 (65.1%) and 72 (29.1%) pts, respectively. The median number of lymph nodes retrieved was 15 (range, 6-64) and that of positive lymph nodes was 2 (range, 0-21). High FDG-uptake was observed in 52 (21.0%) pts, including 6 (2.4%) who had clear postoperative changes, 10 (4.0%) who had a false positive abnormal uptake of whom 6 underwent invasive diagnostic procedures. The PET-CT results modified the management of 36 pts (14.5%) who were found to have true positive findings: 30 (12.1%) were proven to have overt metastatic disease and in 6 (2.4%) a second primary was discovered. With the median follow-up of 39.0 months (range 7.2-98.4 months), of the 30 pts found to be metastatic, 10 (33.3%) underwent curative treatments and are currently with no evidence of disease (NED). Updated data, on more patients and a longer follow-up, will be presented at the meeting. Conclusions: Early postoperative PET-CT changed the staging and treatment of 14.5% of resected stage III pts, and has the potential for early detection of curable metastatic disease. We currently evaluate this strategy and its actual impact in a prospective trial.

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Prognosis of microsatellite instability and/or mismatch repair deficiency stage III colon cancer patients after disease recurrence: Results of an accent meta-analysis of seven studies.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.3525 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 3525-3525 ◽

Cited By ~ 1

Author(s):

Julien Taieb ◽

Levi Pederson ◽

Qian Shi ◽

Steven R Alberts ◽

Norman Wolmark ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Patients ◽

Mismatch Repair ◽

Statistical Significance ◽

Multivariable Analysis ◽

Disease Recurrence ◽

Stage Iii ◽

Wild Type ◽

Poor Prognostic Factor ◽

Stage Iii Colon Cancer

3525 Background: Microsatellite instable/deficient mismatch repair (MSI) metastatic colorectal cancers have been reported to be of poor prognosis. The interaction between MSI and BRAFV600E mutation complicates the picture. Methods: Patients with resected stage III CC from 7 studies with disease recurrence and data available for MSI and BRAFV600E status were analyzed. The primary endpoint was survival after recurrence (SAR) to assess the prognostic roles of MSI and BRAFV600E, respectively. Associations of markers with SAR were analyzed using Cox proportional hazards models adjusted for clinicopathologic features (data collected 12/1998 to 11/2009). Results: Among 2630 patients with cancer recurrence (1491 men [56.7%], mean age, 58.5 [19-85] years), multivariable analysis revealed that patients with MSI tumors (n = 220) had significantly better SAR (adjusted hazard ratio [aHR], 0.82; 95% CI, 0.69-0.98; P = .029) than patients with microsatellite stable /proficient MMR (MSS) tumors (n = 1766). This was also observed when looking at patients treated by the standard FOLFOX adjuvant regimen only (aHR, 0.76; 0.58-1.00; P = .048). Same trends were observed when looking at MSI/dMMR patients outcome in BRAFV600E wild-type (aHR, 0.84; P = .10) and mutant (aHR, 0.88; P = .43) subgroups separately, without reaching statistical significance. As previously described poor SAR was observed in BRAFV600E mutants vs wild type patients (n = 244; aHR, 2.06; 95% CI, 1.73-2.46; P < .0001) and this was also true in BRAFV600E mutants MSI/dMMR patients (n = 77, aHR, 2.65 ; 95% CI, 1.67-4.21; p < .0001). Other factors associated with a poor SAR were : olderage, male gender, T4/N2, proximal primary tumor location, poorly differentiated adenocarcinoma, and early recurrence (by 1y increase). Conclusions: In stage III colon cancer patients recurring after adjuvant chemotherapy and before the era of immuno-oncologic agents, MSI/dMMR was associated with a better survival compared to MSS. BRAFV600E mutation seems to be a poor prognostic factor for both MSI/dMMR and MSS/pMMR patients.

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Palliative oxaliplatin-based chemotherapy after exposure to oxaliplatin in the adjuvant setting for colon cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.753 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 753-753

Author(s):

Renata D'Alpino Peixoto ◽

Aalok Kumar ◽

Sharlene Gill ◽

Howard John Lim

Keyword(s):

Colon Cancer ◽

Progression Free Survival ◽

Population Based ◽

Stage Iii ◽

Metastatic Colon Cancer ◽

Stage Iii Colon Cancer ◽

Metastatic Setting ◽

Cancer Agency ◽

Third Line

753 Background: Little is known regarding the efficacy of oxaliplatin-based chemotherapy for metastatic colon cancer patients who have already received adjuvant oxaliplatin-based chemotherapy. Methods: We retrospectively reviewed 22 consecutive patients who developed recurrence after adjuvant oxaliplatin-based chemotherapy for stage III colon cancer and received another course of oxaliplatin-based chemotherapy for their metastatic disease. The main endpoint was progression-free survival (PFS). Results: 635 patients received oxaliplatin-based chemotherapy for stage III colon cancer at the British Columbia Cancer Agency from 2006 to 2011. 176 pts recurred, 22 (12.5%) of whom were re-exposed to oxaliplatin in the metastatic scenario. Oxaliplatin in combination with fluoropyrimidine was given as first line in 3 pts (13.6%), as second line in 14 (63.6%), and third line in 5 (22.7%). Median time from the last cycle of adjuvant oxaliplatin-based chemotherapy to the first cycle of palliative oxaliplatin-based chemotherapy was 44.3 months. Median PFS and OS were 3.3 (95% CI 1.4-5.1) and 10.0 months (95% CI 5.3-14.6), respectively. There was no difference in PFS for patients who were re-exposed to oxaliplatin in less than 36 months or later than that (3.6 versus 3.1 months, p=0.793, HR=0.88). Conclusions: In this population-based study, only a small proportion of pts who recurred after oxaliplatin-based adjuvant therapy received oxaliplatin in the metastatic setting. Re-exposure of oxaliplatin in combination with fluoropyrimidine is associated with only modest PFS benefit. Larger studies evaluating the role of oxaliplatin re-exposure are needed.

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