Evaluation of management of desmoid tumours associated with familial adenomatous polyposis in Dutch patients

British Journal of Cancer (2011) 104, 37 – 42 & 2011 Cancer Research UK All rights reserved 0007 – 0920/11 www.bjcancer.com MH Nieuwenhuis*,1, EM Mathus-Vliegen2, CG Baeten3, FM Nagengast4, J van der Bijl5, AD van Dalsen6, JH Kleibeuker7, E Dekker2, AM Langers8, J Vecht9, FT Peters7, R van Dam3, WG van Gemert3, WN Stuifbergen10, WR Schouten11, H Gelderblom12 and HFA Vasen1,8 1 The Netherlands Foundation for the Detection of Hereditary Tumours, Rijnsburgerweg 10, Poortgebouw Zuid, 2333 AA Leiden, The Netherlands; Department of Gastroenterology and Hepatology, Academic Medical Centre, Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; 3 Department of Surgery, Maastricht University Medical Centre, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands; 4Department of Gastroenterology, Radboud University Nijmegen Medical Centre, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, The Netherlands; 5Department of Surgery, Atrium Medical Centre Heerlen, Henri Dunantstraat 5, 6419 PC Heerlen, The Netherlands; 6Department of Surgery, Isala Clinics Zwolle, Dokter van Heesweg 2, 8025 AB Zwolle, The Netherlands; 7Department of Gastroenterology and Hepatology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands; 8Department of Gastroenterology and Hepatology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, The Netherlands; 9Department of Gastroenterology and Hepatology, Isala Clinics Zwolle, Dokter van Heesweg 2, 8025 AB Zwolle, The Netherlands; 10Department of Gastroenterology and Hepatology, Elisabeth Hospital Tilburg, Hilvarenbeekseweg 60, 5022 GC Tilburg, The Netherlands; 11Department of Surgery, Erasmus University Medical Centre Rotterdam, Postbus 2040, 3000 CA Rotterdam, The Netherlands; 12Department of Clinical Oncology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, The Netherlands 2 BACKGROUND: The optimal treatment of desmoid tumours is controversial. We evaluated desmoid management in Dutch familial adenomatous polyposis (FAP) patients. METHODS: Seventy-eight FAP patients with desmoids were identified from the Dutch Polyposis Registry. Data on desmoid morphology, management, and outcome were analysed retrospectively. Progression-free survival (PFS) rates and final outcome were compared for surgical vs non-surgical treatment, for intra-abdominal and extra-abdominal desmoids separately. Also, pharmacological treatment was evaluated for all desmoids. RESULTS: Median follow-up was 8 years. For intra-abdominal desmoids (n ¼ 62), PFS rates at 10 years of follow-up were comparable after surgical and non-surgical treatment (33% and 49%, respectively, P ¼ 0.163). None of these desmoids could be removed entirely. Eventually, one fifth died from desmoid disease. Most extra-abdominal and abdominal wall desmoids were treated surgically with a PFS rate of 63% and no deaths from desmoid disease. Comparison between NSAID and anti-estrogen treatment showed comparable outcomes. Four of the 10 patients who received chemotherapy had stabilisation of tumour growth, all after doxorubicin combination therapy. CONCLUSION: For intra-abdominal desmoids, a conservative approach and surgery showed comparable outcomes. For extraabdominal and abdominal wall desmoids, surgery seemed appropriate. Different pharmacological therapies showed comparable outcomes. If chemotherapy was given for progressively growing intra-abdominal desmoids, most favourable outcomes occurred after combinations including doxorubicin. British Journal of Cancer (2011) 104, 37 – 42. doi:10.1038/sj.bjc.6605997 www.bjcancer.com Published online 9 November 2010 & 2011 Cancer Research UK Keywords: desmoid tumour; desmoid-type fibromatosis; familial adenomatous polyposis; management Familial adenomatous polyposis (FAP) is a dominantly inherited cancer predisposition syndrome, caused by mutations in the adenomatous polyposis coli (APC) gene. Carriers of the mutated APC gene develop hundreds to thousands of adenomatous polyps in the colon and rectum, leading to a nearly 100% cancer risk by the age of 40 years (Lynch et al, 2008). By performing a prophylactic colectomy, the risk of death due to colorectal cancer *Correspondence: Dr MH Nieuwenhuis; E-mail: Received 27 July 2010; revised 12 October 2010; accepted 19 October 2010; published online 9 November 2010 is decreased. Among FAP patients, a spectrum of extra-colonic manifestations is often observed, including duodenal cancer and desmoid tumours. These manifestations are currently the most common causes of death after colorectal cancer (Arvanitis et al, 1990). Desmoid tumours or aggressive fibromatoses are histologically benign proliferations of fibro-aponeurotic tissue (Goldblum and Fletcher, 2002). In the general population, the incidence of desmoids is about 3 per million per year, and the tumours are mainly located in the extremities or in the abdominal wall (Fallen et al, 2006). Of all patients presenting with a desmoid tumour, at least 7.5% has FAP or will develop FAP later in life (Nieuwenhuis et al, 2010, submitted for publication). In the total Clinical Studies Evaluation of management of desmoid tumours associated with familial adenomatous polyposis in Dutch patients Management of FAP-related desmoid tumours MH Nieuwenhuis et al 38 Clinical Studies FAP population, desmoid tumours develop in about 10 – 30% and are usually located in the mesentery of the small bowel (Fallen et al, 2006). Desmoids range from small, indolent, or even regressive tumours to large and progressive growing neoplasms causing obstruction of vital organs. Desmoid tumours do not metastasise, although they can present as multifocal disease. Treatment of FAP-related desmoid tumours is controversial (Sleijfer, 2009). As desmoid tumours are rare, and show a variable disease course, the effectiveness of treatment is difficult to determine. There are no randomised controlled trials. Usually, extra-abdominal and abdominal wall desmoid tumours are removed surgically, but two recently published reports argued a wait-and-see policy for patients in which surgery would result in major functional or cosmetic defects (Bonvalot et al, 2008; Stoeckle et al, 2009). For intra-abdominal desmoid tumours, surgery is not recommended because surgical resection is complicated or impossible in most cases, and because of high recurrence rates (Rodriguez-Bigas et al, 1994). Furthermore, there is evidence that tissue damage is a risk factor for desmoid development (Clark et al, 1999; Bertario et al, 2001). The most frequently used pharmacological therapies include non-steroidal anti-inflammatory drugs (NSAIDs), hormonal agents, biological agents, and cytotoxic chemotherapy (Janinis et al, 2003; Tolan et al, 2007). Currently, most guidelines recommend a stepwise approach, starting with NSAIDs (preferably sulindac). If this is not effective, hormonal therapy is added, most commonly consisting of tamoxifen or toremifene (...truncated)