Advanced Dermatofibrosarcoma Protuberans Research Articles

Dermatofibrosarcoma Protuberans; Case Report in a Pediatric Patient

Dermatofibrosarcoma protuberans (DFSP) is a rare and locally aggressive mesenchymal neoplasm arising from the dermal and subcutaneous tissues. It typically manifests as a slow-growing, firm, protuberant or plaque-like lesion on the skin. DFSP predominantly affects young to middle-aged adults, with a slight predilection for females. This tumor exhibits a distinctive infiltrative growth pattern, characterized by tumor cells invading the surrounding tissues, including the deep subcutaneous layers and the underlying fascia. Histopathologically, DFSP presents characteristic features, such as the presence of spindle-shaped tumor cells arranged in a "storiform" pattern, as well as the presence of a prominent "honeycomb" appearance due to the presence of multinucleated giant cells. Immunohistochemical staining is essential to confirm the diagnosis, with positivity for CD34 being a hallmark of DFSP. Although DFSP rarely metastasizes, its extensive local invasion and high recurrence rate necessitate a wide surgical excision with clear margins as the mainstay of treatment. The use of Mohs micrographic surgery or adjuvant radiation therapy has demonstrated favorable outcomes in cases with challenging anatomical locations or microscopically positive margins. Imatinib mesylate, a tyrosine kinase inhibitor, has also emerged as a promising systemic therapy for advanced or unresectable DFSP, particularly cases with the COL1A1-PDGFB gene fusion, which represents the molecular hallmark of DFSP. Early diagnosis and appropriate management are crucial to achieving optimal outcomes in DFSP. This article provides a comprehensive review of the clinical, histopathological, and molecular aspects of DFSP, highlighting the significance of a multidisciplinary approach to ensure accurate diagnosis and tailored therapeutic strategies for patients affected by this rare dermatological neoplasm.

Advanced dermatofibrosarcoma protuberans: an updated analysis of cases from an Indian sarcoma clinic.

Aim:Dermatofibrosarcoma protuberans (DFSP) accounts for less than 2% of all soft-tissue sarcomas.Patients & methods:We retrospectively reviewed our database for patients with locally advanced or metastatic DFSP who had presented to our clinic between January 2016 and January 2020.Results:We identified a total of 14 patients, of whom ten had sarcomatous transformation. Eleven cases had metastatic disease and three were locally advanced. The initial partial response rate to first-line imatinib was 76.9% and the overall median progression-free survival on imatinib was 15 months.Conclusion:We had a high proportion of patients with sarcomatous transformation, in contrast to their relative rarity in the West. While most patients had initial good responses to imatinib, second-line therapies were not as effective.

Long-Term Outcome of Neoadjuvant Tyrosine Kinase Inhibitors Followed by Complete Surgery in Locally Advanced Dermatofibrosarcoma Protuberans.

Simple SummaryWide surgical excision is the standard treatment for dermatofibrosarcoma protuberans. Imatinib mesylate has been reported as an efficient neoadjuvant therapy to surgery in order to reduce tumor size and post-operative relapses for locally advanced or unresectable tumors. The aim of this study was to evaluate the long-term status of patients with advanced dermatofibrosarcoma protuberans treated by neoadjuvant tyrosine kinase inhibitors. Based on the data of 27 patients in our center, locally advanced and unresectable DFSP were efficiently treated with neoadjuvant tyrosine kinase inhibitors followed by complete surgery with micrographic analysis with durable local recurrence disease-free survival and few severe adverse events.In locally advanced dermatofibrosarcoma protuberans (DFSP), imatinib mesylate has been described as an efficient neoadjuvant therapy. This retrospective study included patients with locally advanced DFSP who received neoadjuvant TKI (imatinib or pazopanib) from 2007 to 2017 at Saint Louis Hospital, Paris. The primary endpoint was the evaluation of the long-term status. A total of 27 patients were included, of whom nine had fibrosarcomatous transformation. The median duration of treatment was 7 months. The best response to TKI treatment before surgery, evaluated according to RECIST1.1 on MRI, consisted of complete/partial response (38.5%) or stability (46.2%). DFSP was surgically removed in 24 (89%) patients. A total of 23 patients (85%) were disease-free after 64.8 months of median follow-up (95% confidence interval 47.8; 109.3). One patient developed distant metastases 37 months after surgical tumor resection and finally died. Two patients (7%) did not get surgery because of metastatic progression during TKI treatment, and one patient refused surgery even though the tumor decreased by 30%. Treatment-related adverse events (AE) occurred in 23 patients (85%). Only four patients (imatinib: n = 3, pazopanib: n = 1) had grade ≥3 AE requiring temporary treatment disruption. Neoadjuvant TKI followed by complete surgery with micrographic analysis is an effective strategy for locally advanced and unresectable DFSP, with durable local recurrence disease-free survival.

1703P - Long-term outcome of neoadjuvant tyrosine kinase inhibitors (TKI) in locally advanced dermatofibrosarcoma protuberans (DFSP)

BackgroundImatinib mesylate is approved in unresectable tumors and has been also proposed in the neoadjuvant setting in order to reduce tumor size and post-operative relapses for difficult to resect DFSP. The aim of this study was to evaluate the long-term results of neoadjuvant imatinib and other TKI used in DFSP. MethodsThe files of all patients with the following criteria seen from 2007 to 2017 in our center were collected in this retrospective study: a/histologically proven primary or recurrent DFSP with COL1A1-PDGFB translocation b/ difficult to treat but surgically manageable as assessed in pluridisciplinary tumor board, c/received first-line neoadjuvant TKI (imatinib, pazopanib). The primary endpoint was long-term progression-free survival (PFS). Results27 patients (median 42 years, range: 18-63) were included, of whom 9 (33%) had fibrosarcomatous transformation on pre-TKI biopsy. 10 patients had primary tumors and 17 presented recurrences. Median tumor size was 6cm (range 3-30). 24 patients received imatinib (median dose= 600mg/day), 3 received pazopanib (median dose= 600mg/day) for a median of 7 months. The best MRI response to ITK treatment before surgery according to RECIST1.1 consisted of complete/partial response (33%) or stability (48%). DFSP was surgically removed in 24 patients (89%) after a median of 7 months and 2 surgeries. Two patients (7%) did not receive surgery because of metastasis progression. One other patient declined surgery. 23 of 24 patients surgically treated were disease-free after 50 months of median follow-up (range 10-133). One patient developed distant metastasis 37 months after the complete surgical resection. The median PFS was 44 months (range 10-133).The histological response localization was mainly patchy (n=10) or diffuse (n=7). The median percentage of therapeutic response surface was 65%.Treatment-related adverse events occurred in 23 patients (85%). 4 patients had grade 3 or higher toxicities (2 grade 3 and 4 neutropenia, 1 grade 3 cholestasis, 1 grade 3 nausea) requiring temporary treatment disruption and dose reductions. ConclusionsTKI are effective neoadjuvant treatment for locally advanced or inoperable DFSP with long-term PFS and few severe adverse events. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

S1 guidelines for dermatofibrosarcoma protuberans (DFSP) - update 2018.

While dermatofibrosarcoma protuberans (DFSP) is a rare cancer entity overall, it is nevertheless the most common type of cutaneous sarcoma. The tumor is of fibroblastic origin and characterized by slow, undermining and locally destructive growth. Metastatic spread is very rare. Given its nonspecific clinical appearance, diagnosis is frequently delayed. Biopsy and subsequent histopathology are key diagnostic tools. Standard treatment for primary tumors consists of complete excision with surgical margins of 1 to 2cm. Smaller margins are associated with high local recurrence rates. Inoperable and metastatic DFSP may be treated with radiation therapy. Approximately 80-90% of DFSP lesions harbor a fusion gene that results in continuous activation of the PDGF-β signaling pathway. Consequently, molecular targeted therapy inhibiting PDGF-β is an effective option for advanced (inoperable) and metastatic DFSP. The first agent to be approved for systemic treatment of DFSP is the multikinase inhibitor imatinib, showing objective response rates of about 50% in clinical trials.

Systemic therapy in advanced dermatofibrosarcoma protuberans: Imatinib and beyond.

e22523 Background: Imatinib is the standard treatment of advanced Dermatofibrosarcoma (DFSP). However ideal treatment of advanced DFSP patients, who have progressive disease (PD) on imatinib, remains an unanswered question. Methods: We retrospectively analysed consecutive advanced DFSP patients who presented to AIIMS Sarcoma Medical Oncology clinic between January 2016 and January 2019. Results: There were eleven patients, with median age of 35 years, seven (63.6%) of which were males. Fibrosarcomatous transformation was present in six (54.5%) patients. Four (36.4%) had locally advanced disease, while seven (63.6%) had metastatic disease. Primary site was trunk in eight (63.7%) patients. Three (75%) of the four patients who received neoadjuvant imatinib, underwent complete surgical resection. Initial dose of imatinib was 400mg OD in eight (72.7%) patients, 600 mg OD in two (18.2%) and 800 mg OD in one (9.1%) patient. The best response to imatinib was Partial response (PR) in nine (81.8%) patients, stable disease (SD) in one (9.1%) and primary PD in one (9.1%) patient. Median progression free survival (PFS) was 16 months, after a median follow up of 14 months. Five (45.4%) patients had PD on imatinib. As mentioned in table, strategies used in these patients were pazopanib (n = 3), doxorubicin (n = 2), other chemotherapy (n = 2), dose escalation of imatinib (n = 2) and reintroduction of imatinib (n = 1). One patient had prolonged stable disease on pazopanib, while remaining had PD. Conclusions: Imatinib remains prominent first line therapy in advancved DFSP. Though pazopanib has shown some promise, the treatment outcomes in second line therapy and beyond have largely been dismal and need to be studied prospectively.[Table: see text]

Advanced Dermatofibrosarcoma Protuberans Treatment With Imatinib: Experience From a Dedicated Sarcoma Medical Oncology Clinic in India

PurposeAdvanced dermatofibrosarcoma protuberans (DFSP) is an exceptionally uncommon disease with scarce literature, especially from developing countries. Molecular testing is unfortunately not available in India, and expert diagnosis by a sarcoma pathologist is available only in tertiary care centers.Materials and MethodsWe retrospectively analyzed consecutive patients with inoperable DFSP (on the basis of expert histopathology only) who presented to our sarcoma medical oncology clinic from January 2016 to July 2017.ResultsThere were a total of seven patients, with median age of 35 years, predominantly males (85.7%). Fibrosarcomatous variant and metastatic disease were present in six (85.7%) patients. Partial response rates were 71.4%, and overall disease control was 85.7%. Median progression-free survival was 14 months.ConclusionDFSP diagnosis on the basis of expert histopathology in the absence of translocation can help out in targeted therapy–based treatment until translocation testing becomes available. The fibrosarcomatous variant has poor outcome, and further research is needed to help this group of patients.

EGFR is involved in dermatofibrosarcoma protuberans progression to high grade sarcoma.

Dermatofibrosarcoma protuberans (DFSP), amounting to 6% of all soft tissue sarcomas, has a slow growth rate, contrasting with a likelihood for local recurrence and a 10-20% evolution to higher-grade sarcoma, or “transformed DFSP” (DFSP-T). At molecular level, the characteristic COL1A1-PDGFB rearrangement, leading to sustained PDGFR signaling, is not linked to the evolutive potential. Here, we studied EGFR, another tyrosine kinase receptor, using laser-microdissection to select the different histologic components of DFSP (DFSP center, DFSP infiltrative periphery, DFSP-T higher-grade sarcoma), in 22 patients followed over 3 to 156 months. EGFR protein and mRNA were expressed in 13/22 patients with DFSP or DFSP-T, and increased with tumor progression, both in microdissected areas of higher-grade sarcomas and in microdissected areas of local extension. No cancer-associated EGFR gene mutation or copy-number variation, nor any KRAS, BRAF, NRAS hotspot mutations were found in any microdissected area. Among epithelial-mesenchymal transition factors tested, SNAIL 1/2 had the same expression pattern as EGFR while ZEB1/2 or TWIST1/2 did not. Using a proteome profiler phospho-kinase array on 3 DFSP and 3 DFSP-T cryopreserved tissue samples, EGFR phosphorylation was detected in each case. Among EGFR downstream pathways, we found positive correlations between phosphorylation levels of EGFR and STAT5a/b (r = 0.87, p < 0.05) and TOR (r = 0.95, p < 0.01), but not ERK in the MAPK pathway (r = -0.18, p > 0.70). We thus demonstrated that in DFSP evolution to high grade sarcoma, EGFR and SNAIL were involved, with EGFR activation and signaling through TOR and STAT5a/b downstream effectors, which could lead on to new therapies for advanced DFSP.

Long-term results of treatment of advanced dermatofibrosarcoma protuberans (DFSP) with imatinib mesylate – The impact of fibrosarcomatous transformation

BackgroundDermatofibrosarcoma protuberans (DFSP) is rare, infiltrating dermal neoplasm, characterized by indolent growth and low probability of metastases. The first effective systemic therapy in DFSP introduced into clinical practice was imatinib, demonstrating high activity in advanced cases. The aim of the study was to perform an analysis of patients with advanced DFSP treated with imatinib, with or without surgery, in routine clinical practice with long-term follow-up. Patients and methodsWe analyzed the data of 31 Caucasian patients (14 male, 17 female; median age 56 years) with locally advanced/initially inoperable and/or metastatic DFSP who started therapy with imatinib at initial dose 800 mg daily between 12/2004 and 07/2014. All diagnoses were confirmed cytogenetically for the presence of specific COL1A1-PDGFB fusion. Median follow-up time was 5.3 years. ResultsMetastases were present in 15 cases (8 – lungs, 5 – soft tissue, 2 – lymph nodes). Fibrosarcomatous transformation (FS-DFSP) was confirmed in 16 patients (52%). 5-year progression-free survival (PFS) rate was 58% (median 6.8 years), 5-year overall survival (OS) rate was 64% (median time for OS was not reached). The shorter PFS and OS correlated with FS-DFSP and presence of metastatic disease. 5-year PFS rate was 93% for classic DFSP and 33% for FS-DFSP. The best overall responses were: 21 partial responses (68%, including 8 FS-DFSP, but the responses were shorter than for classic DFSP), 6 stable disease (19%) and 4 progressive diseases (13%). Thirteen patients (47%) underwent resection of residual disease and nine of them remained free of disease, although imatinib was discontinued. Median survival after progression on imatinib was 19 months, and longer survival were observed only in cases were rescue surgery/radiotherapy was possible. ConclusionsOur results indicate the long-term activity of imatinib in therapy of inoperable and/or metastatic cases of DFSP, including FS-DFSP. Some DFSP patients initially evaluated as unresectable/metastatic or necessitating mutilating surgery turned resectable after imatinib therapy and this rational approach leading to complete remission maybe potentially curative.

107. Long-term results of treatment of advanced dermatofibrosarcoma protuberans (DFSP) with imatinib mesylate

107. Long-term results of treatment of advanced dermatofibrosarcoma protuberans (DFSP) with imatinib mesylate

Target therapy of unresectable or metastatic dermatofibrosarcoma protuberans with imatinib mesylate: an analysis on 22 Chinese patients.

Dermatofibrosarcoma protuberans (DFSP) is a rare, plaque-like tumor of the cutaneous tissue occurring more on the trunk than the extremities and neck. More than 95% of DFSP present anomalies on the 17q22 and 22q13 chromosomal regions leading to the fusion of COL1A1 and PDGFB genes. Surgery is the optimal treatment for DFSP, but less effective in locally advanced or metastatic patients, as is the case with chemotherapy and radiotherapy. The aim of this study was to assess retrospectively the therapeutic activity and safety of imatinib on 22 Chinese patients with locally inoperative or metastatic DFSP at a single institution.In the collected data of 367 Chinese patients with DFSP, we analyzed retrospectively 22 patients with locally advanced or metastatic DFSP, all of whom received imatinib therapy at 1 center from January 2009 to October 2014. Patients were administered with imatinib at an initial dose of 400 mg and escalated to 800 mg daily after they developed imatinib resistance. The median follow-up time was 36 months, and the median treatment time was 15 months.The results showed that 10 locally advanced DFSP patients and 12 metastatic DFSP patients received imatinib therapy. Apart from 1 patient who developed primary imatinib resistance, 15 patients achieved partial remission (PR), and 6 patients achieved stable disease (SD). Both fibrosarcomatous DFSP and classic DFSP patients demonstrated similar response to imatinib. Median PFS was estimated to be 19 months. Median overall survival (OS) has not been reached, and estimated 1- and 3-year OS rates were 95.5% (21/22) and 77.3% (17/22), respectively. Four out of 10 patients with primarily unresectable DFSP received complete surgical resection after neoadjuvant treatment of imatinib.Imatinib therapy is well tolerated with a safety profile and is the therapy of choice in locally inoperative or metastatic DFSP. Neoadjuvant treatment of locally advanced or metastatic DFSP with imatinib improves surgical outcomes and may facilitate resection of difficult tumors.

Genetic Aberrations in Imatinib-Resistant Dermatofibrosarcoma Protuberans Revealed by Whole Genome Sequencing

Dermatofibrosarcoma protuberans (DFSP) is a very rare soft tissue sarcoma. DFSP often reveals a specific chromosome translocation, t(17;22)(q22;q13), which results in the fusion of collagen 1 alpha 1 (COL1A1) gene and platelet-derived growth factor-B (PDGFB) gene. The COL1A1-PDGFB fusion protein activates the PDGFB receptor and resultant constitutive activation of PDGFR receptor is essential in the pathogenesis of DFSP. Thus, blocking PDGFR receptor activation with imatinib has shown promising activity in the treatment of advanced and metastatic DFSP. Despite the success with targeted agents in cancers, acquired drug resistance eventually occurs. Here, we tried to identify potential drug resistance mechanisms against imatinib in a 46-year old female with DFSP who initially responded well to imatinib but suffered rapid disease progression. We performed whole-genome sequencing of both pre-treatment and post-treatment tumor tissue to identify the mutational events associated with imatinib resistance. No significant copy number alterations, insertion, and deletions were identified during imatinib treatment. Of note, we identified newly emerged 8 non-synonymous somatic mutations of the genes (ACAP2, CARD10, KIAA0556, PAAQR7, PPP1R39, SAFB2, STARD9, and ZFYVE9) in the imatinib-resistant tumor tissue. This study revealed diverse possible candidate mechanisms by which imatinib resistance to PDGFRB inhibition may arise in DFSP, and highlights the usefulness of whole-genome sequencing in identifying drug resistance mechanisms and in pursuing genome-directed, personalized anti-cancer therapy.

Complete resection of recurrent and initially unresectable dermatofibrosarcoma protuberans downsized by Imatinib

Curative surgical treatment of recurrent, locally advanced dermatofibrosarcoma protuberans is often limited owing to a close relation of the tumor with important anatomical structures. Targeted therapy with imatinib, a tyrosine kinase inhibitor, may cause significant reduction of tumor volume, thereby enabling radical surgery. This treatment strategy, therefore, offers a chance of cure for selected patients with advanced dermatofibrosarcoma protuberans. In addition, preoperative treatment with imatinib may decrease possible disfigurement related to radical surgery for large tumors.

Effective treatment of recurrent, advanced dermatofibrosarcoma protuberans by electrochemotherapy

ejd.2013.1992 Auteur(s) : Katarzyna Wiater1 wiater.katarzyna@gmail.com, Marcin Zdzienicki1, Tadeusz Morysinski1, Hanna Kosela1, Anna Klimczak1, Mariusz Obrebski2, Konrad Ptaszynski3, Piotr Rutkowski1 1 Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Center, Roentgena Str. 5, 02-781 Warsaw, Poland 2 Department of Surgery, Regional Hospital Plock, Poland 3 Department of Pathology, The Medical Center of Postgraduate Education, Warsaw, Poland In April [...]

Dermatofibrosarcoma protuberans-derived fibrosarcoma: Response to escalated-dose imatinib mesylate (IM) and second-generation kinase inhibitor nilotinib.

e20529 Background: Dermatofibrosarcoma protuberans (DFSP) is a dermal sarcoma typically carrying a translocation between chromosomes 17 and 22 that generates functional platelet-derived growth factor B (PDGFB). Imatinib is active in locally advanced and metastatic DFSP harboring t(17;22) with objective response rates of 50% in pooled clinical trial results. Less is known of imatinib, or second generation kinase inhibitor nilotinib, efficacy in fibrosarcomatous-DFSP having the PDGF rearrangement. Methods: From January 2007, 2 patients with locally advanced high grade Fibrosarcoma (FS) arising in DFSP were treated with 400 mg IM. We also identified 4 DFSP and 2 FS patients without DFSP from 2003. Results: Both patients were male age 60/51 with ECOG PS=0. Patient A weighed 142 kg and had a subjective response, RECIST SD and continued PET scan activity. Dose was eventually escalated to 1600 mg. Imatinib trough level = 3710 ng/ml. The shoulder mass was resected with 1mm margin at 29 months. 54% of the cells contained PDGFB rearrangement by FISH. The patient died at 32 months of brain metastsasis. Patient B had RECIST SD and continued PET activity after 4 months of treatment and had 1 month of IM escalation to 800mg. He underwent resection of his abdominal mass but relapsed in the inguinal node and lungs. After three cycles of MAID and two cycles of gemcitabine/docetaxel he was treated with compassionate use nilotinib (Tasigna). He died of disease progression 4 weeks after initiation of nilotinib (OS from presentation 20 months). 49% of the cells contained PDGFB rearrangement at presentation and 63% at resection. Conclusions: resistance to imatinib was not related to PDGFRB expression and was not overcome by dose escalation of imatinib or nilotinib.

Treatment of advanced dermatofibrosarcoma protuberans with imatinib mesylate with or without surgical resection

Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue sarcoma of the skin characterized by the presence of specific COL1A1-PDGFB fusion protein, which appears as a consequence of the t(17;22) (q22;q13) translocation. The aim of the study was to perform an analysis of patients with advanced DFSP treated with imatinib, with or without surgery, in clinical practice outside trials. We analysed the data of 15 patients (6 male, 9 female; median age 56 years) with locally advanced/initially inoperable and/or metastatic DFSP treated with imatinib 400-800 mg daily between 12/2004 and 06/2009. All diagnoses were ascertained cytogenetically (fluorescent in situ hybridization). Median follow-up time was 16 months (range: 4-81). Metastases were present in six cases (two lungs, two soft tissue, two lymph nodes). Fibrosarcomatous transformation (FS-DFSP) was confirmed in seven patients (47%). A 2-year progression-free survival (PFS) rate was 60%, and a 2-year overall survival (OS) rate was 78% (median time for PFS/OS was not reached). The best overall responses were: 10 partial responses (67%, including 5 FS-DFSP-1 progressed during the follow-up), 2 stable diseases (13%) and 3 progressive diseases (20%). Seven patients (47%) underwent resection of residual disease and remained free of disease. We have confirmed the profound anti-tumour effect of imatinib in DFSP harbouring t(17;22) with long-term responses. Imatinib therapy may in some cases lead to tumour resectability of lesser disfiguration.

Neoadjuvant treatment with imatinib for locally advanced dermatofibrosarcoma protuberans.

e20507 Background: We report the cases of five patients with locally advanced dermatofibrosarcoma protuberans (DFSP) of the head and neck and other regions that were treated successfully with neoadjuvant imatinib. The tumors of all patients had molecular evidence of the t(17;22) translocation by FISH and had associated over-expression of the PDGFR. More than 90% of DFSP are characterized by this chromosomal translocation which leads to over-expression of PDGFR. PDGFR is a target for oral imatinib which has been shown to induce significant responses in this entity. Imatinib has been used primarily in advanced DFSP as palliative therapy after the failure of resection and radiotherapy. Methods: These five patients had tumors for which initial surgery was felt to be potentially disfiguring and morbid given their locations and locally advanced nature. Given the known ability of imatinib to induce significant objective responses in unresectable DFSP, the patients were treated with 6 cycles (months) of imatinib therapy prior to surgical resection. Results: All had excellent partial responses. Subsequently, they went on to surgical interventions that were technically easier to perform and less disfiguring. Conclusions: We review these cases in the context of the published literature and conclude that neoadjuvant therapy of locally advanced DFSP with imatinib can lead to significant tumor reduction and hence less disfiguring yet successful resections with better cosmetic outcomes for patients with this uncommon malignancy. No significant financial relationships to disclose.

Imatinib mesylate in advanced dermatofibrosarcoma protuberans: pooled analysis of two phase II clinical trials.

Dermatofibrosarcoma protuberans (DFSP) is a dermal sarcoma typically carrying a translocation between chromosomes 17 and 22 that generates functional platelet-derived growth factor B (PDGFB). Two distinct phase II trials of imatinib (400 to 800 mg daily) in patients with locally advanced or metastatic DFSP were conducted and closed prematurely, one in Europe (European Organisation for Research and Treatment of Cancer [EORTC]) with 14-week progression-free rate as the primary end point and the other in North America (Southwest Oncology Group [SWOG]) with confirmed objective response rate as the primary end point. In the EORTC trial, confirmation of PDGFB rearrangement was required, and surgery was undertaken after 14 weeks if feasible. The SWOG study confirmed t(17;22) after enrollment. Sixteen and eight patients were enrolled onto the EORTC and SWOG trials, respectively. Tumor size ranged from 1.2 to 49 cm. DFSP was located on head/neck, trunk, and limb in seven, 11, and six patients, respectively, and was classic, pigmented, and fibrosarcomatous DFSP in 13, one, and nine patients, respectively. Metastases were present in seven patients (lung involvement was present six patients). Eleven patients (4%) had partial response as best response, and four patients had progressive disease as best response. Median time to progression (TTP) was 1.7 years. Imatinib was stopped in 11 patients because of progression, one patient because of toxicity, and two patients after complete resection of disease. Median overall survival (OS) time has not been reached; 1-year OS rate was 87.5%. Imatinib is active in DFSP harboring t(17;22) including fibrosarcomatous DFSP, with objective response rate approaching 50%. Response rates and TTP did not differ between patients taking 400 mg daily versus 400 mg twice a day.

Locally advanced dermatofibrosarcoma protuberans treated with imatinib followed by Mohs surgery: Results of six cases of a single institution

Locally advanced dermatofibrosarcoma protuberans treated with imatinib followed by Mohs surgery: Results of six cases of a single institution

Neoadjuvant Imatinib Therapy for Dermatofibrosarcoma Protuberans

Dermatofibrosarcoma protuberans (DFSP) is an unusual soft-tissue tumor with a propensity for subclinical extension and local recurrence. Surgical excision, even with tissue-sparing techniques, may cause significant deformity or disability because of the infiltrative nature of DFSP. In this study, we evaluate retrospective data obtained from 4 patients with locally advanced or recurrent DFSP who received neoadjuvant imatinib mesylate therapy before undergoing Mohs micrographic surgery. Patients treated with neoadjuvant imatinib therapy had an average tumor size reduction of 36.9%. This clinical response was paralleled by histopathologic changes, including decreased cellularity in 100% of the total area as well as significant hyalinization. Imatinib therapy for DFSP before Mohs micrographic surgery was associated with 100% local control at a maximum follow-up of 4 years. Neoadjuvant imatinib therapy is a well-tolerated, novel approach to DFSP that reduces tumor burden and facilitates resection. Larger prospective studies are needed to confirm and expand on these results.