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Pathological Complete Response after long-course Neoadjuvant Chemoradiation Therapy for Rectal Cancer: Predictive factors and the impact of smoking status
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: The standard treatment for patients diagnosed with rectal cancer is surgery, and, depending on the clinical stage of the tumor, it is frequently combined with preoperative chemo-radiation therapy (CRT). Preoperative CRT results in pathologic complete response (pCR) in about 10-30% of patients.  Accurate prediction of that response could avoid surgery. The aim of this study was to identify clinical and histopathological predictors of pCR as well as the association between pre-treatment CEA levels and pCR in non-smoking and smoking patients receiving preoperative CRT for rectal cancer.

Methods: One thousand and two hundred and thirty patients diagnosed between 1998 and 2009 with primary rectal adenocarcinoma without any evidence of distant metastasis and operated with a radical total mesorectal excision (TME) resection were identified. A total of 449 patients remained for inclusion in the study after excluding patients with any of the following: no neoadjuvant CRT (n=720) history of pelvic radiation treatment (n=2), previous transanal endoscopic microsurgery or polypectomy of the primary lesion (n=15), concurrent malignant tumor (n=14), and no information about pre- or post-treatment T stage in the chart (n=30). The clinical tumor stage and size were assessed by endorectal ultrasound, MRI, CT, flexible sigmoidoscopy/colonoscopy, chest X-ray and PET-CT. Pathologic complete response was defined as absence of viable tumor cells in the rectal wall and in any of the resected lymph nodes. CRT consisted of a 5-fluorouracil-based regimen and external beam radiation with a mean radiation dose of 50 Gy given over a mean of 5.6 weeks.

Results: Ninety-one patients (20%) achieved pCR and 85 patients (19%) had only microscopic residual disease left at the time of surgery. In patients with pCR, pretreatment tumor size was smaller, 4.2 cm (95% C.I 3.8-4.6 cm) vs. 4.8 cm (95% C.I 4.6-5.0 cm), and pretreatment CEA was significantly lower, 3.4 ng/ml (95% C.I 2.3-4.6 ng/mL) vs. 10.0 ng/mL (95% C.I 7.5-12.5 ng/ml), when compared to the group with no pCR. When stratifying for smoking status, CEA was significantly associated with pCR only in the group with non-smokers (p=0.018). When adjusting for number of cigarettes smoked per week in the multivariate analysis, CEA was no longer significantly associated with pCR.

Conclusions: In non-smokers a low CEA level are significantly associated with pCR. The predictive value of CEA in smokers can be limited and further studies needs to evaluate the impact of smoking on the predictive value of CEA for pCR in rectal cancer.

National Category
URN: urn:nbn:se:uu:diva-159141OAI: oai:DiVA.org:uu-159141DiVA: diva2:442589
Available from: 2011-09-22 Created: 2011-09-22 Last updated: 2011-11-04
In thesis
1. Cancer of the Colon and Rectum: Prognostic Factors and Early Detection
Open this publication in new window or tab >>Cancer of the Colon and Rectum: Prognostic Factors and Early Detection
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Colorectal cancer (CRC) is one of the most common causes of death from malignant disease. Nevertheless, no ideal screening method exists and there is a lack of prognostic and predictive factors to support clinical decisions and to aid the development of a more individualized treatment for patients with CRC. The aim of this thesis was to investigate early detection, prognostic and predictive factors of CRC. In the first paper, a novel method to collect cells for DNA quantification from the rectal mucosa was investigated. The sensitivity and specificity of this test to detect CRC or any pathology in colon and rectum were ultimately too low to be acceptable. In the second paper, the prognostic value of growth differentiation factor 15 (GDF 15) was evaluated in patients curatively operated for colorectal cancer. GDF 15 expression was demonstrated to be associated with a negative prognosis in patients with stages I-III and III disease. In the third paper, the prognostic value of BRAF, PIK3CA KRAS and MSI was evaluated in a cohort of patients with CRC stratified by disease and recurrence. The results indicated that patients with CRC stage III without recurrence have a higher frequency of BRAF mutation compared to stage III patients with recurrence. In the fourth paper, histopathological predictors of pathologic complete response (pCR) as well as the association between pre-treatment carcinoembryonic antigen (CEA) levels and pCR in non-smoking and smoking patients receiving preoperative chemo-radiotherapy for rectal cancer were evaluated. Only in non-smokers was a low CEA level significantly associated with pCR, suggesting that the predictive value of CEA for pCR in rectal cancer in smokers can be limited. In sum, this research has investigated a new method for CRC detection and further evaluated the clinical use of prognostic and predictive markers in CRC.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2011. 83 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 706
colorectal cancer screening predictive markers prognostic markers
National Category
urn:nbn:se:uu:diva-159142 (URN)978-91-554-8166-7 (ISBN)
Public defence
2011-11-04, Hedstrand salen, Akademiska sjuhuset, ing. 70 bv, Uppsala, 13:00 (Swedish)
Available from: 2011-10-14 Created: 2011-09-22 Last updated: 2012-06-14Bibliographically approved

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