Radiation Oncology/Sarcoma/DFSP

Dermatofibrosarcoma Protuberans Epidemiology Cutaneous, locally aggressive, primarily low grade sarcoma ~10% may contain a high-grade fibrosarcoma component Low rate (<5%) of metastasis; higher if fibrosarcoma component Rare, 2-6% of soft tissue sarcomas Adults in 30's Risk factors: pregnancy, arsenic exposure, acanthosis nigricans Clinical Presentation Plaque-like areas of cutaneous thickening Skin-colored, red-brown, or violaceous, particularly at the margins May arise within pre-existing scar or tattoo As it slowly enlarges, becomes raised ("protuberans"), firm, and nodular (fixed to dermis, but moves over deeper structures) At diagnosis, >75% are superficial and <5cm diameter Slow, indolent growth, such that the lesion may be present for years Distribution: Trunk ~50% Lower extremity ~20% Upper extremity 15% Head and neck 15% Work Up MRI helpful to estimate extent of deep extent CT not routinely necessary, unless bony invasion suspected Metastatic workup not routinely necessary, unless suspicion from H&P Histology Cell of origina is not well understood Histochemistry and electron microscopy suggest fibroblast lineage However, the cells are CD34 positive, suggesting possibly dendritic lineage In comparison, dermatofibromas and desmoid tumors are CD34- The tumors show benign-appearing spindle cells, in an irregular patterns resembling a straw mat. In early lesions there is a tumor-free zone with epidermis >90% have a t(17;22) translocation, resulting in a fusion of PDFG-B driven by a highly expressed collagen promoter (COL1A1) Results in PDFGRb activation, which is tyrosine kinase receptor Staging AJCC 7th Edition (2010) First edition to include DFSP Please see the Soft Tissue Sarcoma staging page American Musculoskeletal Tumor Society Staging for DFSP Stage IA - Low or intermediate grade within the subcutaneous compartment Stage IB - Low or intermediate grade extending outside anatomic compartment Stage II - High grade histology Natural History Tends to recur locally after excision alone Recur locally multiple times before metastasis; significant interval before development of metastases. Fibrosarcomatous changes predict for metastatic potential. Treatment Overview Surgical resection is the primary treatment approach Historically, wide local excision with 3cm margins was recommended, down to and including fascia Mohs mapping reveals fine tentacles of tumor, and is becoming favored due to preservation of cosmesis Some recommend modified Mohs to include a final path margin for permanent section Pooled local recurrence rate with adequate margin WLE or Mohs' is <2% Recurrences tend to occur within 3 years of surgery Definitive RT not routinely; only couple reports available Adjuvant radiation is typically indicated if positive or close margins, further resection anatomically not possible if recurrence happens, or recurrent disease Given the high rate of t(17;22) leading downstream to a tyrosine kinase activation, efforts are under way to use Gleevec and other TKIs in this disease Adjuvant Radiation Therapy MD Anderson 2013 (1972-2010) 23628134 -- Dermatofibrosarcoma Protuberans: Long-term Outcomes of 53 Patients Treated With Conservative Surgery and Radiation Therapy. (Castle KO, Int J Radiat Oncol Biol Phys. 2013 Jul 1;86(3):585-90. doi: 10.1016/j.ijrobp.2013.02.024. Epub 2013 Apr 26.) Retrospective. 53 consecutive patients. Surgery and preoperative (13%) or postoperative (87%) RT. Median tumor size 4 cm (1-25 cm). Preop dose 50 Gy, postop dose 60-66 Gy. Gross disease 7%, positive margin 30%. Median F/U 6.5 years Outcome: Recurrence 4%. 5-year and 10-year OS 98%. Fibrosarcomatous change not associated with risk of LR or DM Toxicity: 13%; moderate/severe complications 9% at 10 years Conclusion: DFSP is radioresponse with excellent local control after surgery and RT. Adjuvant RT should be considered if large/recurrent tumor or where attempt at wide surgical margins would result in significant morbidity 1998 9531366 -- "The role of radiation therapy in the management of dermatofibrosarcoma protuberans." (Ball MT, Int J Radiat Oncol Biol Phys. 1998 Mar 1;40(4):823-7. Retrospective. 19 patients receiving adjuvant xrt. 60 Gy given for +microscopic margin; 65 Gy given for gross residual disease. Local control at 10 yrs was 95% Conclusion: adjuvant xrt should be considered for +margins or if adequate wide excision would lead to major cosmetic defect. Soft Tissue Tumours Working Group, The Netherlands Cancer Institute; 1997 9376187 -- Haas RL et al. "The role of radiotherapy in the local management of dermatofibrosarcoma protuberans." 38 consecutive pts w/ DFSP. 21 tx'd surgically, 17 tx'd w/ combined modality. Surgery alone had local control of 67% Combined modality had local control of 82% (many of these who had xrt already had multiple local recurrences. Harvard; 1996 8708729 -- Suit H et al. "Radiation in management of patients with dermatofibrosarcoma protuberans." J Clin Oncol. 1996 Aug;14(8):2365-9. 18 patients treated with postop (n=15) or definitive (n=3) xrt. Population was +/close margins or xrt alone. Local control at 10yrs was 88%.