Optimizing Treatment of Desmoid Tumors

Lev, Dina; Kotilingam, Dhanasekaran; Wei, Caimiao; Ballo, Matthew T.; Zagars, Gunar K.; Pisters, Peter W.T.; Lazar, Alexander J.; Patel, Shreyaskumar; Benjamin, Robert S.; Pollock, Raphael E.

doi:10.1200/jco.2006.10.5015

Cited by 256 publications

(196 citation statements)

References 23 publications

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“…Although some tumors exhibit a significant tendency for local recurrence even in the setting of negative microscopic margins, others do not recur after R1 resection, and some have been observed to spontaneously regress even without therapeutic intervention. 2,46 This interdesmoid tumor heterogeneity suggests the possibility of underlying biological differences; however, relevant molecular prognostic markers are essentially unknown. As has also been observed by others 37,39,40,44 ( Table 5), we have shown that desmoid CTNNB1 mutational spectra are quite limited.…”

Section: Discussionmentioning

confidence: 99%

“…1 Desmoids predominantly affect young adults, especially females, and primarily involve the extremities (including proximal points of attachment at the pelvic and shoulder girdles), the trunk, and the intestinal mesenteries. 2 Desmoid tumors can infrequently occur as part of familial syndromes such as familial adenomatous polyposis (FAP) and familial infiltrative fibromatosis, both identified as caused by a germ-line mutation in the adenomatosis polyposis gene (APC). [3][4][5][6][7][8] However, most desmoids are sporadic and there is a global lack of knowledge regarding risk factors associated with their etiology and development.…”

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confidence: 99%

“…9,10 Although unable to metastasize, these highly infiltrative and locally destructive lesions have a significant tendency to recur, with recurrence rates ranging from 19 to 38% in multiple studies. 2,[11][12][13][14][15][16][17][18][19][20][21][22][23] Currently there are no reliable methods to identify those tumors with a higher risk for recurrence; the molecular determinants of desmoid behavior remain primarily unknown. 23 Surgical resection remains the mainstay of desmoid therapy; however, these tumors frequently require multiple and at times debilitating surgical interventions for their control, resulting in significant treatment-related morbidity such as amputation or loss of significant portions of foregut.…”

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confidence: 99%

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Specific Mutations in the β-Catenin Gene (CTNNB1) Correlate with Local Recurrence in Sporadic Desmoid Tumors

Lazar

Tuvin

Hajibashi

et al. 2008

The American Journal of Pathology

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Desmoid fibromatosis is a rare, nonmetastatic neoplasm marked by local invasiveness and relentless recurrence. Molecular determinants of desmoid recurrence remain obscure. ␤-Catenin deregulation has been commonly identified in sporadic desmoids although the incidence of CTNNB1 (the gene encoding ␤-catenin) mutations is uncertain. Consequently, we evaluated the prevalence of CTNNB1 mutations in a large cohort of sporadic desmoids and examined whether mutation type was relevant to desmoid outcome. Desmoid specimens (195 tumors from 160 patients, 1985 to 2005) and control dermal scars were assembled into a clinical data-linked tissue microarray. CTNNB1 genotyping was performed on a 138-sporadic desmoid subset. Immunohistochemical scoring was performed per standard criteria and data were analyzed using Kaplan-Meier and other indicated methods. CTNNB1 mutations were observed in 117 of 138 (85%) of desmoids. Three discrete mutations in two codons of CTNNB1 exon 3 were identified: 41A (59%) , 45F (33%) , and 45P (8% , excluded from further analysis because of rarity). Five-year recurrence-free survival was significantly poorer in 45F-mutated desmoids (23% , P < 0.0001) versus either 41A (57%) or nonmutated tumors (65%). Nuclear ␤-catenin expression was observed in 98% of specimens and intensity was inversely correlated with incidence of desmoid recurrence (P < 0.01). In conclusion, CTNNB1 mutations are highly common in desmoid tumors. Furthermore, patients harboring CTNNB1 (45F) mutations are at particular risk for recurrence and therefore may especially benefit from adjuvant therapeutic approaches. (Am J Pathol

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Section: Discussionmentioning

confidence: 99%

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Specific Mutations in the β-Catenin Gene (CTNNB1) Correlate with Local Recurrence in Sporadic Desmoid Tumors

Lazar

Tuvin

Hajibashi

et al. 2008

The American Journal of Pathology

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365

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“…Of 155 fibromatosis tissues from all topologies available for DNA sequencing, 101 extra-abdominal fibromatoses were used to investigate the correlation between b-catenin mutational status and clinical characteristics: age, sex, tumour size, tumour location (head and neck, abdominal and thoracic walls and limbs), therapy (including quality of surgical resection as assessed by type of resection (R0, R1, or R2 according to the UICC-R classification system)) (Lev et al, 2007), and outcome (for 101 patients treated with a curative intent). R0 resection was obtained for 42 patients.…”

Section: Patient Population and Clinical Datamentioning

confidence: 99%

High frequency of β-catenin heterozygous mutations in extra-abdominal fibromatosis: a potential molecular tool for disease management

et al. 2010

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BACKGROUND: Fibromatosis comprises distinct clinical entities, including sporadic extra-abdominal fibromatosis, which have a high tendency for recurrence, even after adequate resection. There are no known molecular biomarkers of local recurrence. We searched for b-catenin mutations in a European multicentre series of fibromatosis tumours to relate b-catenin mutational status to disease outcome. METHODS: Direct sequencing of exon 3 b-catenin gene was performed for 155 frozen fibromatosis tissues from all topographies. Correlation of outcome with mutation rate and type was performed on the extra-abdominal fibromatosis group (101 patients). RESULTS: Mutations of b-catenin were detected in 83% of all cases. Among 101 extra-abdominal fibromatosis, similar mutation rates (87%) were observed, namely T41A (39.5%), S45P (9%), S45F (36.5%), and deletion (2%). None of the clinico-pathological parameters were found to be significantly associated with b-catenin mutational status. With a median follow-up of 62 months, 51 patients relapsed. Five-year recurrence-free survival was significantly worse in b-catenin-mutated tumours regardless of a specific genotype, compared with wild-type tumours (49 vs 75%, respectively, P ¼ 0.02). CONCLUSION: A high frequency (87%) of b-catenin mutation hallmarks extra-abdominal fibromatosis from a large multicentric retrospective study. Moreover, wild-type b-catenin seems to be an interesting prognostic marker that might be useful in the therapeutic management of extra-abdominal fibromatosis.

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“…This type of tumor does not metastasize, but is highly locally invasive, and exhibits a propensity for recurrence, even following aggressive surgery with free surgical margin (1). Surgery has been the mainstay of treatment for desmoid tumors; however, there has been controversy about the association between the microscopic margin status and recurrence rates (2)(3)(4)(5)(6)(7)(8)(9), and therefore, no definitive conclusion has been reached regarding the significance of the histological margin status.…”

Section: Introductionmentioning

confidence: 99%

Simple resection of truncal desmoid tumors: A case series

et al. 2016

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Abstract. Desmoid tumors of the extra-abdominal and abdominal wall have been associated with morbidity due to the aggressive nature of the surgery and high recurrence rates. Surgery that does not cause functional impairment is desired for patients with desmoid tumors. In the present study, among patients with desmoid tumors who were prospectively and consecutively treated with identical conservative treatment with meloxicam, a selected patients of patients were treated with less invasive surgery than wide-resection. Out of 60 patients pathologically diagnosed with desmoid tumors, 9 patients with tumors refractory to conservative treatment and 4 patients who refused to receive this type of treatment were treated with planned simple resection. Subsequently, the clinical outcome of the patients and the mutational status of the catenin β-1 (CTNNB1) gene in the tumors were analyzed. The mean age of the 13 patients that underwent planned simple resection was 39 years, and the tumors were located in the abdominal wall in 6 cases, the chest wall in 4 cases and the neck in 3 cases. All excised specimens were evaluated and positive microscopic margins were identified; however, during the mean follow-up period of 30 months, 12/13 cases, 7 of which had T41A mutations and 5 of which had no mutations (wild-type), did not develop recurrence. Only 1 initial case with an S45F mutation in the CTNNB1 gene developed recurrence. The results of the present prospectively treated with simple resection and retrospectively analyzed study suggest that planned simple resection could serve as a therapeutic modality for extraperitoneal desmoid tumors, particularly truncal ones with a wild-type or T41A mutational status.

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Optimizing Treatment of Desmoid Tumors

Cited by 256 publications

References 23 publications

Specific Mutations in the β-Catenin Gene (CTNNB1) Correlate with Local Recurrence in Sporadic Desmoid Tumors

Specific Mutations in the β-Catenin Gene (CTNNB1) Correlate with Local Recurrence in Sporadic Desmoid Tumors

High frequency of β-catenin heterozygous mutations in extra-abdominal fibromatosis: a potential molecular tool for disease management

Simple resection of truncal desmoid tumors: A case series

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