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Nodal involvement in luminal complete response after neoadjuvant treatment for rectal cancer
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Norrköping.
Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Health and Developmental Care, Regional Cancer Center South East Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
2016 (English)In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 42, no 6, 801-807 p.Article in journal (Refereed) Published
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Text
Abstract [en]

Background: Pathological complete response (pCR) after neoadjuvant therapy in rectal cancer is correlated with improved survival. There is limited knowledge on the incidence of pCR at a national level with uniform guidelines. The aim of this prospective register-based study was to investigate the incidence and outcome of pCR in relation to neoadjuvant therapy in a national cohort. Method: All patients abdominally operated for rectal cancer between 2007 and 2012 (n = 7885) were selected from The Swedish Colorectal Cancer Register. Twenty-six per cent (n = 2063) had neoadjuvant therapy with either long or short course radiotherapy with amp;gt;4 weeks delay with the potential to achieve pCR. The primary endpoints were pCR and survival in relation to neoadjuvant therapy. Results: Complete eradication of the luminal tumor, ypTO was found in 161 patients (8%). In 83% of the ypTO the regional lymph nodes were tumor negative (ypTONO), 12% had 1-3 positive lymph nodes (ypTON1) and 4% had more than three positive lymph nodes (ypTON2). There was significantly greater survival with ypTO compared to ypT+ (hazard ratio 0.38 (C.I 0.25-0.58)) and survival was significantly greater in patients with ypTONO compared to ypT0N1-2 (hazard ratio 0.36 (C.I 0.15-0.86)). In ypTO, cT3-4 tumors had the greater risk of node-positivity. The added use of chemotherapy resulted in 10% ypTO compared to 5.1% in the group without chemotherapy (p amp;lt; 0.00004). Conclusion: Luminal pathological complete response occurred in 8%, 16% of them had tumor positive nodes. The survival benefit of luminal complete response is dependent upon nodal involvement status. (C) 2016 Elsevier Ltd. All rights reserved.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD , 2016. Vol. 42, no 6, 801-807 p.
Keyword [en]
Rectal cancer; Complete response; Lymph nodes; Neoadjuvant treatment
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:liu:diva-130432DOI: 10.1016/j.ejso.2016.03.013ISI: 000379559300007PubMedID: 27146960OAI: oai:DiVA.org:liu-130432DiVA: diva2:951179
Available from: 2016-08-07 Created: 2016-08-05 Last updated: 2017-05-02
In thesis
1. Response to neoadjuvant treatment in rectal cancer surgery
Open this publication in new window or tab >>Response to neoadjuvant treatment in rectal cancer surgery
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Rectal cancer is one of the three most common malignancies in Sweden with an annual incidence of about 2000 cases. Current treatment consists of surgical resection of the rectum including the loco-regional lymph nodes in the mesorectum. In advanced cases, neoadjuvant chemo-radiotherapy (CRT) prior to the operative treatment reduces local recurrences and enables surgery. The neoadjuvant treatment can also eradicate the tumour completely, i.e. complete response. This research project was designed to investigate the effects of preoperative radiotherapy/ CRT and analyze methods to predict response to CRT.

Study I investigated the expression of the FXYD-3 protein with immunohistochemistry in rectal cancer, with or without preoperative radiotherapy. The results from the total cohort showed that, strong FXYD-3 expression was correlated to infiltrative tumour growth (p = 0.02). In the radiotherapy group, strong FXYD-3 expression was related to an unfavourable prognosis (p = 0.02). Tumours with strong FXYD-3 expression had less tumour necrosis (p = 0.02) after radiotherapy. FXYD-3 expression in the primary tumour was increased compared to normal mucosa (p=0.008). We concluded that FXYD-3 expression was a prognostic factor in patients receiving preoperative radiotherapy for rectal cancer.

Study II investigated FXYD-3 expression in tumours that developed local recurrences following surgery and compared this with expression in tumours that did not develop local recurrences. There was no difference in the expression of FXYD-3 between the group that developed local recurrences and the group that did not develop local recurrences. There was no difference in survival between those with strong or weak FXYD-3 expression. We concluded that this study could not confirm the findings from study 1 i.e. that FXYD-3 expression has prognostic significance in rectal cancer.

Study III was a register-based study on the incidence and effects of complete response to neoadjuvant treatment. Eight per cent of the patients with adequate CRT to achieve complete response also had a complete histological response of the luminal tumor in the resected bowel. Sixteen per cent of that group had remaining lymph node metastases in the operative specimen. Chemotherapy together with radiotherapy doubled the chance of complete response in the luminal tumour. Patients with remaining lymph node metastases had a lower survival rate compared to those without. We concluded that residual nodal involvement after neoadjuvant treatment was an important factor for reduced survival after complete response in the luminal tumour.

Study IV followed up the results from the previous study by re-evaluating magnetic resonance imaging (MRI)- images in patients with complete tumour response. Two experienced MRI radiologists performed blinded re-staging of post CRT MR- images from patients with complete response in the luminal tumour. One group with lymph node metastases and another one without were studied and the results compared with the pathology reports. The sensitivity, specificity, and positive and negative predicted values for correct staging of positive lymph nodes was 37%, 84%, 70% and 57%. The size of the largest lymph node (4.5 mm, p=0.04) seemed to indicate presence of a tumour positive lymph node. We concluded that MRI couldn’t correctly stage patients for lymph node metastases in patients with complete response to CRT in the luminal tumour.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. 66 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1553
National Category
Cancer and Oncology Surgery Clinical Laboratory Medicine Urology and Nephrology Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-132759 (URN)10.3384/diss.diva-132759 (DOI)9789176856383 (ISBN)
Public defence
2016-12-15, Hasselqvistsalen, Växthuset, Campus US, Linköping, 09:00 (Swedish)
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Available from: 2016-11-23 Created: 2016-11-23 Last updated: 2017-05-02Bibliographically approved

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Loftås, PerArbman, GunnarFomichov Casaballe, VictoriaHallböök, Olof
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Division of Clinical SciencesDepartment of Surgery in NorrköpingFaculty of Medicine and Health SciencesFaculty of Health SciencesDepartment of Medical and Health SciencesRegional Cancer Center South East SwedenDepartment of Surgery in Linköping
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