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Table of Contents
Year : 2019  |  Volume : 2  |  Issue : 1  |  Page : 74-75

Head-and-neck dermatofibrosarcoma protuberans: Where does imatinib 'fit in'?

1 Department of Medical Oncology, State Cancer Institute, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India
2 Department of Medical Oncology, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India

Date of Web Publication9-Sep-2019

Correspondence Address:
Avinash Vijaykumar Pandey
Department of Medical Oncology, State Cancer Institute/RCC, Indira Gandhi Institute of Medical Sciences, Patna, Bihar
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/CRST.CRST_46_19

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How to cite this article:
Pandey AV, Singh A. Head-and-neck dermatofibrosarcoma protuberans: Where does imatinib 'fit in'?. Cancer Res Stat Treat 2019;2:74-5

How to cite this URL:
Pandey AV, Singh A. Head-and-neck dermatofibrosarcoma protuberans: Where does imatinib 'fit in'?. Cancer Res Stat Treat [serial online] 2019 [cited 2020 Aug 3];2:74-5. Available from: http://www.crstonline.com/text.asp?2019/2/1/74/266463

Dermatofibrosarcoma protuberans (DFSP) is a rare, locally aggressive cutaneous sarcoma with low malignant potential, especially the fibrosarcoma variant.[1] About 13% of DFSP involves the head-and-neck region where up-front wide local excision with a generous margin is technically challenging and comes with a high probability of close or positive marginal resections. Moreover, for larger tumors, reconstruction is often needed, which is cosmetically unappealing.[2] DFSP is also a radiosensitive tumor, and the use of radiotherapy can reduce local recurrences postresection by one-third to half in patients with inevitable positive or close margins.[3] Adjuvant radiotherapy in the head-and-neck region brings along with it long-term musculoskeletal and cutaneous toxicity, which, sometimes, leads to dysmorphic appearances with indurated skin texture in an otherwise young active healthy population.[4]

DFSP is characterized by translocation of chromosomes 17 and 22 which places the platelet-derived growth factor-beta (PDGF-β) gene under the control of constantly activated Col1A gene, leading to an uninhibited proliferative signal.[5] Imatinib mesylate with single-agent activity against PDGF-β is a rational therapeutic choice in recurrent, unresectable, and metastatic DFSP. Imatinib use is an exciting proposition as it can lead to partial remissions in 35%–40% of patients and another 40% of patients achieve durable disease stabilization without cosmetic decay with good tolerability in advanced or recurrent cases.[6] Its use in borderline operable DFSP as induction therapy to achieve wide excision with acceptable margins ultimately leading to higher local control rates cannot be overemphasized. However, this approach in head–and-neck DFSP has been insufficiently explored due to the rarity of the disease and paucity of literature regarding indications, dose and duration of imatinib use in up-front unresectable cases, and lack of data regarding the extent of conversion rates to operable tumors.

In an original article accompanying this issue of the Journal, a retrospective single tertiary cancer center experience with imatinib use in recurrent, advanced, and metastatic head-and-neck DFSP is presented.[7] It is interesting to note that the majority of patients had high-risk features such as over 50% had a tumor size more than 5 cm, with 44% having fibrosarcoma variant and one-third patients presenting with metastatic disease. Justifiably, the above high-risk cohort had 55% local recurrence rates, reiterating the head-and-neck region as a major graveyard among the DFSP sites. The above results could also be partially attributed to a referral bias in a tertiary center with an intrainstitutional bias for sending high-risk cases for subsequent therapy in the Medical Oncology Department. Eight of the nine patients who received imatinib in the neoadjuvant, recurrent, or metastatic settings had undergone wide excision at some point during the course of their entire treatment with a median recurrence-free survival of 82 months; however, none underwent Mohs micrographic surgery which is known to produce lower local failure rates.

It is also worthy to note that of three patients with borderline operable head–and-neck DFSP, imatinib, when used as neoadjuvant therapy, yielded 66% partial response rates with all three achieving wide excision with negative margins. These patients subsequently went on to receive adjuvant imatinib for a median of 2 years with a recurrence-free survival of 90 months. This is similar to what has been reported in a Phase II trial, although in a non head-and-neck region.[8] In contrast to this, patients prescribed imatinib for palliative intent had only a 33% response rate with two of three patients developing progressive disease on therapy leading to a progression-free survival of just 10 months. These outcomes are worse than what have been earlier described in the literature where imatinib has been used in advanced metastatic patients, probably due to higher risk factors and the head-and-neck location of DFSP in the current study.[6] Although numbers are too small to justify bold conclusions, it seems prudent that imatinib use should be pushed earlier in the sequence of therapeutic options to achieve higher control rates with durable outcomes as delegating it to use later in metastatic cases makes it perform weaker against the aggressive phenotypical expression of disease driven by the higher mutational burden.

The author also described three patients who went on to receive adjuvant imatinib in recurrent cases with close margins and on long follow-up are disease free. This further strengthens the argument to place imatinib on a higher pedestal when disease burden is low in an attempt to derive maximum benefit, especially in head-and-neck DFSP where recurrence rates are higher, and stakes of cosmetic disfigurement are amplified for salvage surgery in recurrent cases often leading to reconstructive surgery to slice wide margin in eloquent locations. However, due to the rarity of DFSP in the head-and-neck and relatively long recurrence-free survival with longer overall survival, prospective systematic randomized control trials to answer the question of the optimal sequence of imatinib use along with dose and duration of prescription, especially in the neoadjuvant and adjuvant settings, seem difficult and mere wishful thinking in the near future. The treatment decision as to where imatinib should 'fit' in the sequence of therapy needs to be individualized and customized depending on the subsite in the head-and-neck region, size of tumor, availability of skilled surgeons, and high-end radiotherapy services with the expectation of better cosmetic outcome and goal of sustained durable control rates.

  References Top

Bowne WB, Antonescu CR, Leung DH, Katz SC, Hawkins WG, Woodruff JM, et al. Dermatofibrosarcoma protuberans: A clinicopathologic analysis of patients treated and followed at a single institution. Cancer 2000;88:2711-20.  Back to cited text no. 1
Kreicher KL, Kurlander DE, Gittleman HR, Barnholtz-Sloan JS, Bordeaux JS. Incidence and survival of primary dermatofibrosarcoma protuberans in the United States. Dermatol Surg 2016;42 Suppl 1:S24-31.  Back to cited text no. 2
Chen YT, Tu WT, Lee WR, Huang YC. The efficacy of adjuvant radiotherapy in dermatofibrosarcoma protuberans: A systemic review and meta-analysis. J Eur Acad Dermatol Venereol 2016;30:1107-14.  Back to cited text no. 3
Fromm M, Littman P, Raney RB, Nelson L, Handler S, Diamond G, et al. Late effects after treatment of twenty children with soft tissue sarcomas of the head and neck. Experience at a single institution with a review of the literature. Cancer 1986;57:2070-6.  Back to cited text no. 4
Sirvent N, Maire G, Pedeutour F. Genetics of dermatofibrosarcoma protuberans family of tumors: From ring chromosomes to tyrosine kinase inhibitor treatment. Genes Chromosomes Cancer 2003;37:1-9.  Back to cited text no. 5
Rutkowski P, Van Glabbeke M, Rankin CJ, Ruka W, Rubin BP, Debiec-Rychter M, et al. Imatinib mesylate in advanced dermatofibrosarcoma protuberans: Pooled analysis of two phase II clinical trials. J Clin Oncol 2010;28:1772-9.  Back to cited text no. 6
Kashyap L, Noronha V, Patil V, Joshi A, Mahajan A, Mittal N, Prabhash K. Dermatofibrosarcoma protuberans of head and neck: Clinical outcome of nine cases treated with imatinib. Cancer Res Stat Treat 2019;2:112-8.  Back to cited text no. 7
  [Full text]  
Ugurel S, Mentzel T, Utikal J, Helmbold P, Mohr P, Pföhler C, et al. Neoadjuvant imatinib in advanced primary or locally recurrent dermatofibrosarcoma protuberans: A multicenter phase II DeCOG trial with long-term follow-up. Clin Cancer Res 2014;20:499-510.  Back to cited text no. 8

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