Update on Sarcomas of the Head and Neck. Kevin Harrington

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1 Update on Sarcomas of the Head and Neck Kevin Harrington

2 Overview Classification and incidence of sarcomas Clinical presentation Challenges to treatment Management approaches Prognostic factors Radiation-induced sarcomas Aggressive fibromatosis

3 Overview Classification and incidence of sarcomas Clinical presentation Challenges to treatment Management approaches Prognostic factors Radiation-induced sarcomas Aggressive fibromatosis

4 Classification and Incidence Soft tissue sarcoma 1% malignant tumours 10% soft tissue sarcomas arise in the head and neck region Bone sarcoma 0.2% malignant tumours 1 5% bone sarcomas arise in the bones of skull and face 1. Ries LAG, Kosary CL, Hankey BF (1999). SEER Cancer Statistics Review National Cancer Institute, Bethesda, MD. 2. National Cancer Intelligence Network (2012). Soft tissue sarcoma: Incidence and survival.

5 Taxonomy of Soft Tissue Sarcoma

6 Head and neck soft tissue sarcoma agestandardised incidence rates (England: ) Head and neck soft tissue sarcoma age-specific incidence rates (England: ) ASR (per million) ASIR (per million) Year of diagnosis Males Females Age at diagnosis Males Females Persons

7 Proportion of patients with head and neck soft tissue sarcomas treated surgically (England ) Proportion of patients treated 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 64% 59% 57% 61% 62% 60% 60% 45% 30% Age at diagnosis Surgery No ST No HES

8 Soft tissue sarcomas of the head and neck region most common histological diagnoses at each age group (England: ) % 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Leiomyosarcoma Angiosarcoma RMS Chondrosarcoma Dermatofibrosarcoma Fibrosarcoma Liposarcoma MFH MPNST Sarcoma, NOS Other

9 Skull and facial bone sarcoma age-standardised incidence rates (England: ) Skull and facial bone sarcoma age-specific incidence rates (England: ) ASR (per million) ASIR (per million) Year of diagnosis Males Females Age at diagnosis Males Females Persons

10 Variation with age in the proportion of skull and facial skeletal bone sarcoma patients treated with surgery (England: ) Proportion of patients treated 100% 90% 80% 70% 60% 50% 40% 69% 73% 75% 30% 65% 64% 58% 62% 66% 20% 39% 10% 0% Age at diagnosis Surgery No ST No HES

11 Overview Classification and incidence of sarcomas Clinical presentation Management approaches Challenges to treatment Prognostic factors Radiation-induced sarcomas Aggressive fibromatosis

12 Head and Neck Sarcomas: 4 broad groups Lesions in the neck (including larynx/pharynx) Liposarcoma, MPNST, Synovial sarcoma Lesions in scalp and facial skin Angiosarcoma, Dermatofibrosarcoma protuberans Lesions in sinonasal tract MPNST, Haemangiosarcoma, Myxofibrosarcoma, RMS Lesions in oral cavity LMS, RMS

13 Mass Lesions In Typical or Atypical Sites Osteosarcoma Pleomorphic sarcoma Chondrosarcoma Synoviosarcoma

14 Mucosal Lesions Poorly Differentiated Cancer Angiosarcoma

15 Cutaneous Lesions Multifocal Pleomorphic Sarcoma

16 Paediatric/Adolescent Lesions Alveolar RMS Embryonal RMS

17 Overview Classification and incidence of sarcomas Clinical presentation Challenges to treatment Management approaches Prognostic factors Radiation-induced sarcomas Aggressive fibromatosis

18 Biology of Sarcomas Diverse histology Wide spectrum of clinical behaviour Limitations in obtaining wide surgical margins Higher local recurrence rate Poor disease specific survival May arise post-irradiation Natural history Low incidence lymph node metastases (3-10%) Distant metastases ~28%

19 Histological Variation de Bree Oral Oncol 2010; 46: 786

20 Non-Evidence-Based Practice Numerous histological subtypes Multiple anatomical sites (head and neck rare) Wide spectrum of clinical behaviour Few randomised studies UK single centre experiences Pooled analysis

21 UK Datasets 1. Birmingham : 36 patients, 24 seen, 12 advised Mean follow-up 50 months: 42% local recurrence rate (by 2 years), 5 year overall survival 49% 2. UCL : 25 patients (17 osteosarcoma jaw) Mean follow 60 months: 18% local recurrence, 80% overall survival 3. RMH : 103 cases, Median follow up 50 months: 5 year local control 47%, 5 year overall survival 50% : 236 pts, 47 benign (9 fibromatosis), 100 primary, 89 recurrent 15 angiosarcomas, 12 DFSP, 11 Ewing s, 4 fibrosarcoma, 4 leiomyosarcoma, 10 liposarcoma, 6 MPNST, 15 MFH, 11 RMS, 6 sarcoma NOS, 8 synovial sarcoma (numerous histotypes) 1. Singh 2008 Sarcoma 2. Ketabachi 2011 Br J Oral Maxfax 3. Eeles 1993 BJC

22 Overview Classification and incidence of sarcomas Clinical presentation Challenges to treatment Management approaches Prognostic factors Radiation-induced sarcomas Aggressive fibromatosis

23 General Management Recommendations Radiology review (CT + MRI) Pathology review Sarcoma MDT discussion Neoadjuvant chemotherapy in selected cases (Ewing s, Osteosarcoma, Synoviosarcoma) Surgery as mainstay of treatment in most (adult) cases Radiotherapy, commonly in post-operative setting

24 Diagnosis: Specialist Pathology Review Core biopsy Pathology review by designated sarcoma pathologist Parallel referral to designated sarcoma MDT HN sarcoma pathology reviews changed 33-48% cases 1-3 In 41 patients HN sarcomas 4 7% not sarcoma 39% sarcoma subtype changed (initially thought to be fibrosarcoma and malignant fibrous histicytoma) In 30 patients, a third of patients treated for head and neck liposarcomas had an initial misdiagnosis 5 1. Bentz 2005 Ann Sur Oncol 2. Eeles 1993 BJC 3. Lajer 2005 Clin Otolaryngol 4. De Bree 2006 Oral Oncol 5. Davis 2009 Head and Neck

25 Leiomyosarcoma Liposarcoma Fibroblastic sarcoma Rhabdomyosarcoma alveolar and embryonal subtype EpSSG RMS 2005 protocol Synovial sarcoma Vascular sarcoma Primary treatment of soft tissue sarcoma Soft tissue Ewing s sarcoma Euro-Ewing's protocol STS other rare variants Kaposi s sarcoma Nerve sheath tumours Sarcoma NOS Radiation induced sarcomas 5th Royal Marsden Head and Neck Cancer Conference Hen's teeth and horse feathers...an evidence-based approach to the management of less common head and neck pathologies

26 Role of Chemotherapy EORTC adjuvant chemotherapy (doxorubicin, ifosfamide, lenograstim) demonstrated no survival benefit, 5 yr OS 68% 1 RMS and Ewings neoadjuvant programmes defined Consider in relatively chemo ensitive cases, particularly on the neoadjuvant setting Synovial sarcoma Angiosarcoma Adjuvant chemotherapy Radiation-induced sarcoma Woll et al

27 Role of Radiotherapy Pre-op versus post-op (50 Gy vs 66 Gy) Extremity STS, RT improves local control rates 1 Pre-operative RT increases post-operative wound complications Local control rates: 75-85% at 5 years Indications G2/G3, deep-seated tumours with close resection margins HN Sarcomas 35 patients Surgery +RT Local control rates ~40-50% G2/G cases: Surgery 52% vs Surgery with radiation 90% 3 In post-operative setting RT >60 Gy in 30 fractions 1. O Sullivan 2002 Lancet 2. Fayda 2009 J Craniomaxfac Surg 3. Tran 1992 Cancer

28 Role of Radiotherapy in STS Target volume definition may differ Patterns of spread dependent on histological subtype Follow fascial planes rather than lymphatic drainage Prescribed doses differ according to histological type Could we consider preoperative RT in selected histotypes Synovial Myxoid liposarcomas (uncommon) Cases with high probability of positive resection margin Cases where post-operative RT will not be possible because of proximity of critical structures

29 Role of Radiotherapy Generally recommended post-op RT as unable to achieve clear resection margins IMRT Proton Therapy Chordoma Chondrosarcoma

30 Brachytherapy

31 Brachytherapy Set-Up

32 6 weeks Post-Treatment

33 Overview Classification and incidence of sarcomas Clinical presentation Challenges to treatment Management approaches Prognostic factors Radiation-induced sarcomas Aggressive fibromatosis

34 Prognostic factors Local recurrence Margins Grade Size>5cm de Bree Oral Oncol 2010; 46: 786

35 Prognostic factors Overall Survival Grade Margins Size>5cm de Bree Oral Oncol 2010; 46: 786

36 Overall survival: bone and soft tissue sarcomas 100% 100% % Relative survival 80% 60% 40% 20% % Relative survival 80% 60% 40% 20% STS Bone STS- excluding skin Bone 0% % Years from diagnosis Years from diagnosis Head and neck bone and soft tissue sarcoma 1-5 year relative survival (England, ) Head and neck bone and soft tissue sarcoma 1-5 year relative survival (England, ) Excluding Skin

37 Overview Classification and incidence of sarcomas Clinical presentation Challenges to treatment Management approaches Prognostic factors Radiation-induced sarcomas Aggressive fibromatosis

38 Overview Classification and incidence of sarcomas Clinical presentation Challenges to treatment Management approaches Prognostic factors Radiation-induced sarcomas Aggressive fibromatosis

39 Aggressive Recurrent Disease

40 Management of Fibromatosis Proliferation of well differentiated myofibroblasts and fibroblasts, low to moderate mitotic activity Locally aggressive Surveillance, some regress spontaneously Medical therapy Tamoxifen +NSAID Liposomal doxorubicin Surgery RT considered in recurrent disease/ inoperable disease and have exhausted systemic treatments 1 1. Keus 2013 Ann Oncol

41 Conclusions Manage patients in a specialist MDT Surgery is the mainstay of treatment in most cases Some histotypes are v chemo- or radiosensitive and may allow avoidance of surgery Post-operative RT almost always recommended Radiation-induced sarcoma is difficult to manage Radiotherapy can be useful in fibromatosis

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