Title: Utility of neoadjuvant therapy in rectal GIST. Authors: Víctor López-López, Juan Ángel Fernández, Pascual Parrilla

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1 Title: Utility of neoadjuvant therapy in rectal GIST Authors: Víctor López-López, Juan Ángel Fernández, Pascual Parrilla DOI: /reed /2016 Link: PubMed (Epub ahead of print) Please cite this article as: López-López Víctor, Fernández Juan Ángel, Parrilla Pascual. Utility of neoadjuvant therapy in rectal GIST. Rev Esp Enferm Dig doi: /reed /2016. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

2 CE 4751 inglés Utility of neoadjuvant therapy in rectal GIST Víctor López-López, Juan Ángel Fernández and Pascual Parrilla Department of General Surgery and Digestive Diseases. Hospital Clínico Universitario Virgen de la Arrixaca. Murcia, Spain Correspondence: Víctor López-López Key words: GIST. Rectum. Imatinib. Neoadjuvant. Local resection. Dear Editor, A neoadjuvant therapy approach with tyrosine kinase inhibitors (TKI) in cases of rectal gastrointestinal stromal tumors (GIST) allows a surgical rescue of a high percentage of patients that initially were not candidates for aggressive surgery. Case report A 49-year-old man presented with a tumor located 3 cm to 1 cm from the anal verge. A GIST was confirmed by a biopsy (CD-117: +/DOG1: +). Magnetic resonance imaging (MRI) showed a tumor in the right anterolateral wall of the rectum. 18 F-FDG PET/CT showed an abnormal uptake of the lesion with a maximum standardized uptake value (SUV) of 9 (Fig. 1A). Neoadjuvant treatment with 400 mg/day of imitanib was initiated. Three months later an 18 F-FDG PET/CT was performed with the absence of pathological uptake (Fig. 1B). A transanal rectal resection was performed. Pathological anatomy identified tumor cells which were positive for CD-117 and DOG-1 and viable tumor (< 5%) with a tumor free surgical margin (Fig. 2). Eighteen months later, the patient is free of disease. Discussion

3 Neoadjuvant therapy decreases tumor size and improves tumor resectability, R0 resection rates and the possibility of organ preservation (1,2). Rectal GIST surgery aims to achieve an R0 resection with minimal morbidity and mortality. In this regard, it is possible to opt for radical surgery, which would reduce the rate of recurrence and thus increase R0 resections but with a high morbidity and mortality (3). In contrast, a local surgery reduces the rate of complications but increases the percentage of incomplete resections and recurrence. Therefore, the current trend is to use imatinib (4,5) in the neoadjuvant setting in order to decrease tumor size and facilitate a local resection with minimal morbidity and mortality and a high R0 resection rate. Acknowledgments The authors would like to thank doctors Juan Luján Mompeán and Belén Ferri. References 1. Wilkinson MJ, Fitzgerald JE, Strauss DC, et al. Surgical treatment of gastrointestinal stromal tumour of the rectum in the era of imatinib. Br J Surg 2015;102: Jakob J, Mussi C, Ronellenfitsch U, et al. Gastrointestinal stromal tumor of the rectum: Results of surgical and multimodality therapy in the era of imatinib. Ann Surg Oncol 2013;20: Agaimy A, Vassos N, Märkl B, et al. Anorectal gastrointestinal stromal tumors: A retrospective multicenter analysis of 15 cases emphasizing their high local recurrence rate and the need for standardized therapeutic approach. Int J Colorectal Dis 2013;28: Liu H, Yan Z, Liao G, Yin H. Treatment strategy of rectal gastrointestinal stromal tumor (GIST). J Surg Oncol 2014;109: Tielen R, Verhoef C, Van Coevorden F, et al. Surgical management of rectal gastrointestinal stromal tumors. J Surg Oncol 2013;107:320-3.

4 a b Fig F-FDG PET/TC before and after neoadjuvant treatment with imatinib. A.18F-FDG PET/TC showed a focal accumulation within the lesion in the right anterolateral wall of the lower third of the rectum before neoadjuvant treatment. B. 18 F-FDG PET/TC without pathological uptake after neoadjuvant treatment. Fig. 2. Pathological anatomy after neoadjuvant treatment. A. The rectal wall with submucous and intramuscular neoplasia consisting mainly of fibro-hyaline stroma with focal calcifications (arrow) and the remains of a viable GIST consisting of spindle cells (arrowhead) (H-E 2x). B. Viable tumor cells (H-E 4x). C. Weak cytoplasmic and paranuclear positivity for CD-117 (10x). D. Intense cytoplasmic positivity for DOG-1 (10x).

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