Radiation Oncology/Benign/Desmoid

Desmoid Tumors

Etiology

• Deep fibromatosis; clinically diverse neoplasms
  • Originally described as a tumor of the abdominal wall in women who were recently pregnant, but can arise at any site in the body in both men and women
  • "Desmos" means band-like or tendon-like
  • Frequently arise in association with fascia, aponeurosis, and associated muscle
  • Potential for large growth, local invasion, and frequent local recurrence if not widely excised
  • Do not metastasise
  • Can be fatal due to local destruction of vital structures
• Incidence: ~900 cases in U.S.
• Three biologic groups:
  • Sporadic
  • Familial adenomatous polyposis (FAP)-associated (Gardner's syndrome)
    • Predilection for surgical sites, typically after colectomy or pouch creation within the abdomen/pelvis
    • May be unresectable as they diffusely infiltrate the mesentery
    • May lead to 10% death rate of these patients
    • Appear to be associated with increased beta-catenin levels due to dysregulation of FAP
  • Familial or multicentric

Clinical Presentation

• Deeply seated, painless, slowly-enlarging mass
• Intra-abdominal desmoids can also present with intestinal obstruction, bowel ischemia, or functional deterioration, particularly in bowel anastomotic sites
• Location:
  • Extra-abdominal (60%)
  • Abdominal wall (25%)
  • Intra-abdominal (15%)

Radiology

• CT and/or MRI
• There are no imaging characteristics that can reliably distinguish desmoid from malignant lesions

Histology

• Incisional biopsy preferred to have a higher confidence in benign vs malignant distinction (UpToDate 2010)
• Monoclonal fibroblastic proliferation, appearing as small bundles of spindle cells in fibrous stroma
• Infiltrative process resembles low-grade fibrosarcoma, but cells lack nuclear and cytoplasmic features of malignancy
• IHC stains for vimentin, smooth muscle actin, and nuclear beta-catenin (see above). Typically negativer for desmin, CKs, and S100

Staging

• No staging system used routinely
• AJCC staging excludes desmoids
• Clevelan Clinic proposed a system for FAP-associated intra-abdominal tumors

• Cleveland Clinic; 2008 PMID 18322756 -- "A desmoid tumor-staging system separates patients with intra-abdominal, familial adenomatous polyposis-associated desmoid disease by behavior and prognosis." (Church J, Dis Colon Rectum. 2008 Jun;51(6):897-901. Epub 2008 Mar 6.)
  • Stage I — Asymptomatic, ≤10 cm, not growing
  • Stage II — Mildly symptomatic, ≤10 cm, not growing
  • Stage III — Moderately symptomatic or bowel/ureteric obstruction, or 10-20 cm in maximal diameter, or slowly growing
  • Stage IV — Severely symptomatic or >20 cm, or rapidly growing

Treatment

• Close observation may be a reasonble strategy for stable, asymptomatic desmoids
  • They may grow progressively larger over time, but growth is indolent, and periods of growth arrest are not uncommon
  • Disease-specific mortality is <1% for sites outside the abdomen
  • Intra-abdominal tumors, particularly if they are FAP-associated, may have 10% mortality rate due to local progression
• Treatment is indicated for symptomatic patients, for cosmetic concerns, or for risk to adjacent structures
• Surgical resection with wide local margin is the goal, though this may not be feasible in many circumstances
  • Local failure after excision 25%-40%
  • However, it's not completely clear if positive surgical margin impacts the ultimate rate of recurrence
  • Role for postop RT is not clear, and is currently not recommended for R1 resection, though it may be offered for R2 resection, particularly if there are concerns about local disease progression and morbidity/mortality (UpToDate 2010)
• Definitive radiation therapy
  • Dose 50-60 Gy
  • Local control in 70-80%
• Systemic therapy
  • Appealing for intra-abdominal tumors
  • NSAIDs or tamoxifen or cytotoxic chemotherapy

Comparative Review

• South Carolina; 2000 (1983-1998) PMID 10738207 -- "Surgery versus radiation therapy for patients with aggressive fibromatosis or desmoid tumors: A comparative review of 22 articles." (Nuyttens JJ, Cancer. 2000 Apr 1;88(7):1517-23.)
  • Literature review. 22 studies. Surgery vs surgery + RT vs RT alone
  • Outcome: Local control surgery 61% (SM- 72% vs SM+ 41%); surgery + RT 75% (SM- 94% vs SM+ 75%); RT alone 78% (significantly higher than surgery group)
  • Toxicity: RT complications fibrosis, paresthesias, edema, fractures
  • Conclusion: RT or surgery + RT results in significantly better local control than surgery alone