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Determining the use of preoperative (chemo)radiotherapy in primary rectal cancer according to national and international guidelines
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
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2019 (English)In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 136, p. 106-112Article in journal (Refereed) Published
Abstract [en]

Background: Pre-operative radiotherapy (RT) or chemoradiotherapy (CRT) is frequently used prior to rectal cancer surgery to improve local control and survival. The treatment is administered according to guidelines, but these recommendations vary significantly between countries. Based on the stage distribution and risk factors of rectal cancers as determined by magnetic resonance imaging (MRI) in an unselected Swedish population, the use of RT/CRT according to 15 selected guidelines is described. Materials and methods: Selected guidelines from different countries and regions were applied to a wellcharacterized unselected population-based material of 686 primary non-metastatic rectal cancers staged by MRI. The fraction of patients assigned to surgery alone or surgery following pre-treatment with (C) RT was determined according to the respective guideline. RT/CRT administered to rectal cancer patients for other reasons, for example, for organ preservation or palliation, was not considered. Results: The fraction of patients with a clear recommendation for pre-treatment with (C) RT varied between 38% and 77% according to the different guidelines. In most guidelines, CRT was recommended to all patients who were not operated directly, and, in others, short-course RT was also recommended to patients with intermediate risk tumours. If only non-resectable or difficult to resect tumours were recommended pre-treatment, as stated in many Japanese publications, 9% would receive CRT followed by a delay to surgery. Conclusions: According to most guidelines, well over 50% of primary non-metastatic rectal cancer patients from a general population, in which screening for colorectal cancer is not practised, are recommended treatment with pre-operative/neo-adjuvant therapy. (C) 2019 Elsevier B. V. All rights reserved. Radiotherapy and Oncology

Place, publisher, year, edition, pages
ELSEVIER IRELAND LTD , 2019. Vol. 136, p. 106-112
Keywords [en]
Rectal cancer, Radiotherapy, Chemoradiotherapy, Clinical guidelines
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-390807DOI: 10.1016/j.radonc.2019.03.036ISI: 000472490500015PubMedID: 31015111OAI: oai:DiVA.org:uu-390807DiVA, id: diva2:1343726
Available from: 2019-08-19 Created: 2019-08-19 Last updated: 2023-01-25Bibliographically approved
In thesis
1. Staging and therapy response in rectal cancer
Open this publication in new window or tab >>Staging and therapy response in rectal cancer
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Every year, around 2,200 individuals are diagnosed with rectal cancer in Sweden. As a result of better tumour staging using magnetic resonance imaging (MRI), pre-operative radiotherapy (with or without chemotherapy), and improved surgery, outcome has improved substantially during the past few decades. Today less than 5% of patients experience a local recurrence. Treatment response is highly variable, up to 30% of patients have a complete remission (CR) after pre-treatment while others do not benefit from the treatment. The aim of this thesis was to investigate factors associated with CR in rectal cancer as accurate response prediction already at the time of diagnosis could enable a personalized treatment approach. For this purpose, an unselected rectal cancer cohort of approximately 1,200 patients diagnosed between 2010-2018 was built.

Paper I provides a description of tumour stages and other MRI characteristics required for the treatment decision in the rectal cancer cohort. In this unselected patient population, most tumours belonged to the risk groups with intermediate or high risk of recurrence and are thus recommended to pre-treatment.

In Paper II, the proportions of patients recommended pre-treatment according to different guidelines were investigated to better understand the wide variability in treatment seen worldwide. This study concluded that between 38% and 77% of non-metastatic patients are presently recommended pre-operative treatment according to 15 international guidelines, when strictly applied to our non-selected rectal cancer cohort.   

To achieve a more personalized treatment approach and a stricter use of pre-treatment, predictive factors of tumour remission are needed. In Paper III an evaluation of the predictive capacity of all clinical and pathological factors used in the staging of rectal cancer prior to treatment decision was done. In Paper IV a combination of clinical and sequencing data was used in analyses to further assess associations with CR and which factors impact prognosis. Tumour size, stage, tumour marker CEA and treatment were predictive of CR. Moreover, genetic factors such as mutated SMAD4 and SYNE1 were associated with CR but further investigations are needed to determine clinical relevance. Mutated KRAS was an independent predictor of non-CR. BRAF V600E mutation increased the risk of recurrence. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2023. p. 55
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1899
Keywords
Rectal cancer, radiotherapy, chemoradiotherapy, complete remission, response prediction, prognosis, targeted sequencing
National Category
Cancer and Oncology
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-493860 (URN)978-91-513-1695-6 (ISBN)
Public defence
2023-03-17, Rudbecksalen, Rudbecklaboratoriet, Dag Hammarskjölds väg 20, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2023-02-22 Created: 2023-01-25 Last updated: 2023-02-22

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Hammarström, KlaraImam, IsraaKorsavidou Hult, NafsikaEkström, JoakimSjöblom, TobiasGlimelius, Bengt

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