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Adult Head and Neck Soft Tissue Sarcomas: Treatment and Outcome

Adult Head and Neck Soft Tissue Sarcomas: Treatment and Outcome Hindawi Publishing Corporation Sarcoma Volume 2008, Article ID 654987, 5 pages doi:10.1155/2008/654987 Clinical Study Adult Head and Neck Soft Tissue Sarcomas: Treatment and Outcome 1 2 3 2 Rabindra P. Singh, Robert J. Grimer, Nabina Bhujel, Simon R. Carter, 2 2 Roger M. Tillman, and Adesegun Abudu King’s College Hospital, Denmark Hill, London SE5 9RS, UK Royal Orthopaedic Hospital, Bristol Road South, Birmingham B31 2AP, UK Oral and Maxillofacial Surgery, University Hospitals Birmingham, Birmingham B15 2TH, UK Correspondence should be addressed to Robert J. Grimer, rob.grimer@btopenworld.com Received 21 June 2007; Revised 26 November 2007; Accepted 12 February 2008 Recommended by Martin Robinson We have retrospectively analysed the experience of a musculoskeletal oncological unit in the management of adult head and neck soft tissue sarcomas from 1990 to 2005. Thirty-six patients were seen, of whom 24 were treated at this unit, the remainder only receiving advice. The median age of the patients was 46 years. Most of the sarcomas were deep and of high or intermediate grade with a median size of 5.5 cm. Eleven different histological subtypes were identified. Wide excision was possible only in 21% of the cases. 42% of the patients developed local recurrence and 42% developed metastatic disease usually in the lungs. Overall survival was 49% at 5 years. Tumour size was the most important prognostic factor. Adult head and neck soft tissue sarcomas have a high mortality rate with a high risk of local recurrence and metastatic disease. The rarity of the disease would suggest that centralisation of care could lead to increased expertise and better outcomes. Copyright © 2008 Rabindra P. Singh et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1. INTRODUCTION there is only one published study that is based in a UK hos- pital in the last 15 years [4]. Most of the series which are publishedhavereportedoutcome over anumberofdecades Soft tissue sarcomas of the head and neck are rare mesenchy- possibly to compensate for the rarity of the disease and to in- mal malignant neoplasms accounting for less than 10% of all crease the size of the study sample for meaningful statistical soft tissue sarcomas and approximately 1% of all head and analysis [6]. However, the spanning of studies over several neck neoplasms [1–5]. Nevertheless, they represent an im- decades has an important drawback in that changes in the portant group of tumours and are associated with significant management of sarcomas and their outcome are not always morbidity and mortality. accurately reflected. There are several histological subtypes of sarcomas which We report on our experience of the management of adult present with a variety of clinical characteristics and many head and neck soft tissue sarcomas presenting to a regional often require treatment with combination of surgery, radio- sarcoma centre based at an orthopaedic hospital over the past therapy, and chemotherapy. They are best treated in special- 20 years. ist sarcoma units where expert multidisciplinary approach to management is possible. In the UK, surgical management of soft tissue sarcomas in the head and neck region is under- 2. METHODS taken by otolaryngologists, maxillofacial surgeons, as well as by musculoskeletal sarcoma surgeons, depending on the lo- We have prospectively collected patient, tumour, treatment, cation of the lesion. and outcome data on all patients with bone and soft tissue Reflecting the rarity of the disease, there is currently a sarcomas for over 20 years at the Royal Orthopaedic Hospital scarcity of studies in the literature and, to our knowledge, (Birmingham, UK). We have identified all patients with soft 2 Sarcoma tissue sarcomas in the head and neck, defined as sites above Eleven different histological subtypes were identified, of the level of the clavicle. We have included all patients seen at which malignant peripheral nerve sheath tumour (MPNST) the unit between 1990 and 2005. was the commonest subtype (25%, n = 6). The histological We have made a number of observations related to pa- subtypes are listed in Table 2. tient demographics, tumour variables, treatment modalities, outcome, and follow up for patients with head and neck soft 3.3. Treatment tissue sarcomas. Tumours were classified as deep if they were deep to the investing fascia whilst they were superficial if The principles of treatment used at the Unit during this time they lay purely in the subcutaneous tissues. The margins of consisted of planned wide local excision followed by radio- excision were classified according the method of Enneking therapy for all high-grade tumours >5 cm or where there [7] with a wide margin being one in which a clear layer of were close margins of excision. normal tissue lay between the tumour and the excision mar- Eight patients were treated with surgery alone as initial gin. A marginal excision was when the excision plane passed treatment for their sarcomas. 13 patients had surgery and through the reactive zone around the tumour (clear but close) postoperative radiotherapy. Two of the three patients who and an intralesional excision was when tumour was incised had Ewing’s sarcoma received neoadjuvant chemotherapy, at any part of the operation, even if a subsequent wide ex- surgery, and postoperative radiotherapy; and one received cision was achieved. Survival was estimated using Kaplan chemotherapy and surgery. The documented margins of ex- Meiersurvivalcurvesand wasdeterminedfor overall5-year cision were intralesional in 10 (42%), marginal in 9 (37%), survival, and the log rank method was used to analyse the and wide in 5 (21%). influence of various prognostic factors on survival of the pa- tients. For situations where no events had arisen in one sub- group, chi-square testing was used to assess possible signifi- 3.4. Local control cance. Institutional approval for this study was obtained. The patients were followed up for an average period of 50 3. RESULTS months. Local recurrence arose in 10 patients (42%) at a me- dian time of 14 months (range 5–96 months) following ini- 3.1. Patients tial treatment. One of the two patients with a low-grade su- perficial sarcoma developed local recurrence and 9 of the 22 A total of 36 patients with head and neck soft tissue sarcomas with high- or intermediate-grade sarcomas developed local were seen during the study period, 24 of whom were treated recurrence. Local recurrence was strongly related to margins at this unit. This is approximately 2% of the total 1912 cases achieved, arising in six of the ten with an intralesional mar- of all soft tissue sarcomas seen at this unit during the same gin (60%), three of the nine with a marginal margin (33%), period. The median age of the patients was 46 years with a and one of the five with a wide margin (20%). range from 16 to 83 years. There were 24 male and 12 female Of the ten patients who developed local recurrence, four patients (M : F = 2:1). were either known to have systemic metastases already or Thirty-five of the sarcomas were located in the neck were found to have synchronous metastases at the time of and one was located in the scalp. The average duration of restaging. All four received palliative treatment and all died symptoms experienced by patients prior to diagnosis was 54 at a median of 9 months from diagnosis of the local recur- weeks (range 1–416 weeks) and the most commonly reported rence. Six patients with local recurrence had no evidence symptom was the presence of a painless lump. of metastases when they developed the local recurrence and The rest of the observations and analysis are based on the were treated aggressively with further surgical excision and 24 patients who received treatment at this unit. We have ex- radiotherapy when possible, often requiring extensive surgi- cluded 12 patients who were either referred for advice only cal reconstructions in order to obtain wide margins of exci- (9 patients) and received definitive treatment elsewhere or sion. Two of these patients subsequently developed metas- who presented with local recurrence and/or metastases after tases 6 and 12 months later, respectively, and both subse- previous failed treatment (3 patients). Various observations quently died. The other four patients remained disease-free on tumours, treatment, local control, and outcome are sum- at a mean of 52 months following their local recurrence. marised in Table 1. 3.5. Metastases 3.2. Tumours The median tumour size was 5.5 cm (range 0.6–13 cm) at di- Ten patients (42%) developed metastatic disease at a median agnosis. 18 of the sarcomas (75%) were deep to the investing time of 17 months (range 0–139 months). Eight patients de- fascia, the rest superficial to the fascia. Two of the sarcomas veloped lung metastases and two lymph node metastases. All were low grade (18%), the rest intermediate (42%, n = 10) or of the patients with concomitant or previous local recurrence high grades (50%, n = 12). All tumours which were located subsequently died as did two of the others without local re- deep to the fascia were of high or intermediate grade. Only currence. Two patients underwent surgical resection of lung one patient (with a Ewing’s sarcoma) had lung metastases at metastases and remained alive and disease-free at a median the time of presentation. of 17 months. Rabindra P. Singh et al. 3 Table 1: Patient age, tumour factors, treatment, local recurrence, and outcome. MPNST: malignant peripheral nerve sheath tumour, DFSP: dermatofibrosarcoma protuberans, MFH: malignant fibrous histiocytoma, SEF: sclerosing epithelioid fibrosarcoma, CT: chemotherapy, RT: radiotherapy. Local Case Age Size Surgical Outcome Diagnosis Depth Definitive treatment Trojani grade recurrence no. (yrs) (cm) margin (months) (months) Leiomyosarcoma Subcutaneous Excision 138 0.6 High Wide Alive, 45 Ewing’s sarcoma Deep CT + excision 222 1.5 High Wide Alive, 208 DFSP Subcutaneous Excision 341 1.7 Intermediate Marginal Alive, 20 DFSP Subcutaneous Excision 424 2 Low Wide Alive, 37 MPNST Subcutaneous Excision 519 3 Intermediate Wide Alive, 36 Ewing’s sarcoma Deep CT + excision + RT 620 4 High Intralesional Alive, 74 Spindle cell sarcoma Deep Excision 741 4 Intermediate Intralesional 8 Alive, 21 864 Spindle cell sarcoma 4 Deep Intermediate Excision + RT Marginal 16 Died, 33 939 MPNST 5 Deep High Excision + RT Intralesional 26 Died, 52 10 53 SEF 5 Deep Intermediate Excision Wide 49 Alive, 139 11 62 Myxoid chondrosarcoma 5 Deep Intermediate Excision Marginal 96 Alive, 157 12 77 MFH 6 Deep High Excision + RT Intralesional 5 Died, 22 13 54 Myxofiibrosarcoma 6.5 Deep High Excision + RT Marginal Alive, 14 14 22 Synovial sarcoma 7 Deep High Excision + RT Intralesional Alive, 35 15 38 MPNST 7 Deep High Excision + RT Intralesional Died, 14 16 50 MPNST 7 Deep Intermediate Excision + RT Marginal Alive, 191 17 65 Liposarcoma 7 Deep High Excision + RT Intralesional 12 Died, 16 18 32 MPNST 8 Deep Intermediate Excision + RT Marginal Alive, 13 19 68 Spindle cell sarcoma 9 Subcutaneous High Excision + RT Wide Alive, 12 20 73 Liposarcoma 9 Deep High Excision + RT Intralesional 41 Died, 51 21 30 Ewing’s sarcoma 10 Deep High CT + excision + RT Intralesional 12 Died, 14 22 48 Synovial sarcoma 10 Deep Intermediate Excision + RT Marginal Alive, 11 23 65 MPNST 10 Deep Intermediate Excision + RT Marginal Died, 45 24 33 Liposarcoma 13 Subcutaneous Low Excision Marginal 8 Alive, 51 Table 2: Histological subtypes. MPNST: malignant peripheral confidence limits (plus or minus 13%) (Figure 1). We inves- nerve sheath tumour, DFSP: dermatofibrosarcoma protuberans, tigated the following factors for possible significance on sur- MFH: malignant fibrous histiocytoma, SEF: sclerosing epithelioid vival. fibrosarcoma. (i) Size. Only 1 patient with a primary sarcoma >5cm has Subtypes No. of patients (%) yet survived more than 5 years whilst the survival for MPNST 6 (25%) patients with tumours ≤5 cm was 71% at 5 years (p = Ewing’s sarcoma 3 (13%) 0.02) (Figure 2). Liposarcoma 3 (13%) (ii) Grade. Neither of the two patients with low-grade tu- mours died but 8 of the 22 with high- or intermediate- Spindle cell sarcoma 3 (13%) grade tumours died (P = .29) (chi-square). Synovial sarcoma 2 (8%) (iii) Depth. None of the 6 patients with subcutaneous sar- DFSP 2 (8%) comas died but 8 of the 18 with deep tumours died Myxofibrosarcoma 1 (4%) (P = .0455) (chi-square). Leiomyosarcoma 1 (4%) (iv) Margin. Six of the 10 patients with intralesional and MFH 1 (4%) two of the 9 patients with a marginal surgical margin Myxoid Chondrosarcoma 1 (4%) died, however none of the 5 patients with a wide sur- SEF 1 (4%) gical margin died (P = .04). (v) Age. We could find no effect of age on survival. Combining these factors revealed that all deaths arose in 3.6. Survival the patients with high- or intermediate-grade deep tumours. Eight patients died at a median time of 2.3 years from diag- When further stratified by size, this showed that two of the nosis. Overall survival was 48.6% at five years but with wide seven patients with high-grade deep tumours ≤5 cm died 4 Sarcoma Our unit is a musculoskeletal unit that takes referrals of pa- tients with both proven or suspected sarcomas. In the case of the head and neck tumours, some were referred directly to us 0.8 for investigation and diagnosis whilst others were referred af- ter a biopsy or imaging had confirmed the diagnosis of a sar- 0.6 coma. We treated patients with sarcomas that were confined to the superficial tissues or deep muscles of the head and neck 0.4 and we have not included patients with soft tissue sarcomas involving the facial skeleton or the oropharynx which pose 0.2 even greater challenges in treatment [6]. Our management policy was based on principles used in treating soft tissue sarcomas at other sites. The head and neck 0 2 4 6 8 1012 14 1618 poses particular problems however because of the proxim- Time (years) ity of so many important structures and the near impossibil- ity of obtaining wide surgical margins in many cases. Unlike Figure 1: Overall 5-year survival. limb soft tissue sarcomas, there is no fallback option of doing an amputation if local recurrence arises. The local recurrence rates for high-grade soft tissue sar- comas after surgical excision have been reported to be as high as 50% in the literature [3, 9, 10]. 42% of patients developed 0.8 Up to 5 cm local recurrence in our study, most arising within 2 years of treatment. Barker et al. in their study reported the median 0.6 time to local recurrence after treatment with surgery and/or radiotherapy to be 4 months, and Kraus et al. reported that 0.4 patients who developed local recurrence did so within 3 years [11, 12]. Over 5 cm 0.2 The risk of local recurrence was higher with intralesional or marginal surgical margins as has been shown by other au- p = 0.02 thors [2, 12]. In view of this, every effort should be made to maximise the margins that can be achieved at the time of the 0 2 4 6 8 1012 14 1618 first surgical procedure, if necessary by going back and doing Time (years) a further wide excision if the initial margins prove positive. Figure 2: Overall survival by size of sarcoma. All patients should have their case discussed at a multidisci- plinary team meeting and the option of radiotherapy consid- ered to try and decrease the risk of local recurrence. Even if patients do develop local recurrence, their case is not hope- compared with 6 of the 11 with high-grade deep tumours less and further excision should be considered. Clearly, how- >5cm (P = .04). ever, initial wide surgical margins should always be aimed for. The commonest site for metastases was the lungs which 4. DISCUSSION was also the commonest cause of death. Mendenhall et al. [3] suggested that patients should undergo a chest CT be- Head and neck sarcomas are rare and the paucity of stud- fore treatment and also suggested that in the absence of pul- ies about their management and outcome testifies to this. monary metastases, other distant metastases are highly un- Head and neck lumps are common and have a variety of likely. We concur with this. diagnoses [2, 3]. Early detection and diagnosis is clearly es- The5-yearsurvivalrateof49% in ourstudy (Figure 1)is sential. The National Institute for Health and Clinical Excel- comparable to a previous UK study by Eeles et al. [4]based lence (NICE) guidance 2005 to all UK general practitioners at the Royal Marsden Hospital of London. They analysed 103 emphasises that “In patients with an unexplained lump in the cases seen over 44 years between 1944 and 1988 and reported neck which has recently appeared or a lump which has not been 50% overall 5-year survival rate. This is similar to the results diagnosed before that has changed over a period of 3 to 6 weeks, reported by Bentz et al. [6] from Memorial Sloan Kettering an urgent referral should be made” [8]. Whilst more general Cancer Centre. Most authors agree that the same prognostic advice is also given about lumps elsewhere in the body: “In factors apply to sarcomas no matter where they arise—grade, patients presenting with a palpable lump, an urgent referral for size, and depth. In the head and neck, however, local recur- suspicion of soft tissue sarcoma should be made if the lump is rence has more sinister portents because of the difficulty of (i) greater than about 5 cm in diameter, subsequent management [5, 13–18]. (ii) deep to fascia, fixed, or immobile, Obtaining local control is paramount in managing these (iii) painful, head and neck sarcomas. Obtaining wide margins may of- (iv) increasing in size, ten require a multidisciplinary team consisting of a sar- (v) a recurrence after previous excision.” coma surgeon, a head and neck surgeon and a reconstructive Cum. survival Cum. survival Rabindra P. Singh et al. 5 surgeon. A clinical oncologist is an essential part of the team prospective series,” World Journal of Surgery,vol. 27, no.7,pp. 875–883, 2003. to advise about radiotherapy usage. A metaanalysis pub- [11] J. L. Barker Jr., A. C. Paulino, S. Feeney, T. McCulloch, and lished in Lancet revealed that chemotherapy did not pro- H. Hoffman, “Locoregional treatment for adult soft tissue sar- duce a survival benefit in the treatment of soft tissue sarco- comas of the head and neck: an institutional review,” Cancer, mas [19]. The same analysis did, however, show a 10% ben- vol. 9, no. 1, pp. 49–57, 2003. efit of chemotherapy on recurrence-free survival. Adjuvant [12] D. H. Kraus, S. Dubner, L. B. Harrison, et al., “Prognostic fac- chemotherapy is not usually advocated for localised soft tis- tors for recurrence and survival in head and neck soft tissue sue sarcomas but can be considered for metastatic disease as sarcomas,” Cancer, vol. 74, no. 2, pp. 697–702, 1994. a palliative treatment. [13] Q.-T.X.Le, K. K. Fu,S.Kroll,etal., “Prognosticfactors in Recent guidance from NICE, UK [20] in the manage- adult soft-tissue sarcomas of the head and neck,” International ment of patients with sarcomas has highlighted the impor- Journal of Radiation Oncology Biology Physics, vol. 37, no. 5, tance of referring all patients with soft tissue sarcomas to a pp. 975–984, 1997. sarcoma centre where they can be managed by a multidis- [14] R. S. Weber, R. S. Benjamin, L. J. Peters, J. Y. Ro, O. Achon, ciplinary team (MDT). The guidance has also emphasised and H. Goepfert, “Soft tissue sarcomas of the head and neck the importance of close collaboration between these sarcoma in adolescents and adults,” The American Journal of Surgery, MDTs and site-specific head and neck surgeons and oncolo- vol. 152, no. 4, pp. 386–392, 1986. gists. This has been emphasised by the recent paper of Harb [15] H. Willers, E. B. Hug, I. J. Spiro, J. T. Efird, A. E. Rosenberg, et al. [21]. We recommend that all surgeons who identify a and C. C. Wang, “Adult soft tissue sarcomas of the head and neck treated by radiation and surgery or radiation alone: pat- suspected or proven soft tissue sarcoma of the head and neck terns of failure and prognostic factors,” International Journal of should refer that patient to a sarcoma MDT and that all head Radiation Oncology Biology Physics, vol. 33, no. 3, pp. 585–593, and neck cancer MDTs should have close links with the local sarcoma MDT for management of these cases. [16] J. Le Vay, B. O’Sullivan, C. Catton, et al., “An assessment of prognostic factors in soft-tissue sarcoma of the head and REFERENCES neck,” Archives of Otolaryngology—Head & Neck Surgery, vol. 120, no. 9, pp. 981–986, 1994. [1] A.I.Farhood,S.I.Hajdu,M.H.Shiu, andE.W.Strong, “Soft [17] S. B. Dudhat, R. C. Mistry, T. Varughese, A. R. Fakih, and R. tissue sarcomas of the head and neck in adults,” The American F. 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Enneking, S. S. Spanier, and M. A. Goodman, “A sys- tem for the surgical staging of musculoskeletal sarcoma,” Clin- ical Orthopaedics and Related Research, vol. 153, pp. 106–120, [8] National Institute for Health and Clinical Excellence. Refer- ral guidelines for suspected cancer, June 2005, http://www .nice.org.uk/page.aspx?o=cg027. [9] J.T.Parsons,R.A.Zlotecki,K.A.Reddy,T.P.Mitchell, R. B. Marcus Jr., and M. T. Scarborough, “The role of radio- therapy and limb-conserving surgery in the management of soft-tissue sarcomas in adults,” Hematology/Oncology Clinics of North America, vol. 15, no. 2, pp. 377–388, 2001. [10] B. O’Sullivan, P. Gullane, J. Irish, et al., “Preoperative radio- therapy for adult head and neck soft tissue sarcoma: assess- ment of wound complication rates and cancer outcome in a MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 International Journal of Journal of Immunology Research Endocrinology Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Submit your manuscripts at http://www.hindawi.com BioMed PPAR Research Research International Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Research and Treatment Cellular Longevity Neurology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Sarcoma Hindawi Publishing Corporation

Adult Head and Neck Soft Tissue Sarcomas: Treatment and Outcome

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Copyright © 2008 Rabindra P. Singh et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Hindawi Publishing Corporation Sarcoma Volume 2008, Article ID 654987, 5 pages doi:10.1155/2008/654987 Clinical Study Adult Head and Neck Soft Tissue Sarcomas: Treatment and Outcome 1 2 3 2 Rabindra P. Singh, Robert J. Grimer, Nabina Bhujel, Simon R. Carter, 2 2 Roger M. Tillman, and Adesegun Abudu King’s College Hospital, Denmark Hill, London SE5 9RS, UK Royal Orthopaedic Hospital, Bristol Road South, Birmingham B31 2AP, UK Oral and Maxillofacial Surgery, University Hospitals Birmingham, Birmingham B15 2TH, UK Correspondence should be addressed to Robert J. Grimer, rob.grimer@btopenworld.com Received 21 June 2007; Revised 26 November 2007; Accepted 12 February 2008 Recommended by Martin Robinson We have retrospectively analysed the experience of a musculoskeletal oncological unit in the management of adult head and neck soft tissue sarcomas from 1990 to 2005. Thirty-six patients were seen, of whom 24 were treated at this unit, the remainder only receiving advice. The median age of the patients was 46 years. Most of the sarcomas were deep and of high or intermediate grade with a median size of 5.5 cm. Eleven different histological subtypes were identified. Wide excision was possible only in 21% of the cases. 42% of the patients developed local recurrence and 42% developed metastatic disease usually in the lungs. Overall survival was 49% at 5 years. Tumour size was the most important prognostic factor. Adult head and neck soft tissue sarcomas have a high mortality rate with a high risk of local recurrence and metastatic disease. The rarity of the disease would suggest that centralisation of care could lead to increased expertise and better outcomes. Copyright © 2008 Rabindra P. Singh et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1. INTRODUCTION there is only one published study that is based in a UK hos- pital in the last 15 years [4]. Most of the series which are publishedhavereportedoutcome over anumberofdecades Soft tissue sarcomas of the head and neck are rare mesenchy- possibly to compensate for the rarity of the disease and to in- mal malignant neoplasms accounting for less than 10% of all crease the size of the study sample for meaningful statistical soft tissue sarcomas and approximately 1% of all head and analysis [6]. However, the spanning of studies over several neck neoplasms [1–5]. Nevertheless, they represent an im- decades has an important drawback in that changes in the portant group of tumours and are associated with significant management of sarcomas and their outcome are not always morbidity and mortality. accurately reflected. There are several histological subtypes of sarcomas which We report on our experience of the management of adult present with a variety of clinical characteristics and many head and neck soft tissue sarcomas presenting to a regional often require treatment with combination of surgery, radio- sarcoma centre based at an orthopaedic hospital over the past therapy, and chemotherapy. They are best treated in special- 20 years. ist sarcoma units where expert multidisciplinary approach to management is possible. In the UK, surgical management of soft tissue sarcomas in the head and neck region is under- 2. METHODS taken by otolaryngologists, maxillofacial surgeons, as well as by musculoskeletal sarcoma surgeons, depending on the lo- We have prospectively collected patient, tumour, treatment, cation of the lesion. and outcome data on all patients with bone and soft tissue Reflecting the rarity of the disease, there is currently a sarcomas for over 20 years at the Royal Orthopaedic Hospital scarcity of studies in the literature and, to our knowledge, (Birmingham, UK). We have identified all patients with soft 2 Sarcoma tissue sarcomas in the head and neck, defined as sites above Eleven different histological subtypes were identified, of the level of the clavicle. We have included all patients seen at which malignant peripheral nerve sheath tumour (MPNST) the unit between 1990 and 2005. was the commonest subtype (25%, n = 6). The histological We have made a number of observations related to pa- subtypes are listed in Table 2. tient demographics, tumour variables, treatment modalities, outcome, and follow up for patients with head and neck soft 3.3. Treatment tissue sarcomas. Tumours were classified as deep if they were deep to the investing fascia whilst they were superficial if The principles of treatment used at the Unit during this time they lay purely in the subcutaneous tissues. The margins of consisted of planned wide local excision followed by radio- excision were classified according the method of Enneking therapy for all high-grade tumours >5 cm or where there [7] with a wide margin being one in which a clear layer of were close margins of excision. normal tissue lay between the tumour and the excision mar- Eight patients were treated with surgery alone as initial gin. A marginal excision was when the excision plane passed treatment for their sarcomas. 13 patients had surgery and through the reactive zone around the tumour (clear but close) postoperative radiotherapy. Two of the three patients who and an intralesional excision was when tumour was incised had Ewing’s sarcoma received neoadjuvant chemotherapy, at any part of the operation, even if a subsequent wide ex- surgery, and postoperative radiotherapy; and one received cision was achieved. Survival was estimated using Kaplan chemotherapy and surgery. The documented margins of ex- Meiersurvivalcurvesand wasdeterminedfor overall5-year cision were intralesional in 10 (42%), marginal in 9 (37%), survival, and the log rank method was used to analyse the and wide in 5 (21%). influence of various prognostic factors on survival of the pa- tients. For situations where no events had arisen in one sub- group, chi-square testing was used to assess possible signifi- 3.4. Local control cance. Institutional approval for this study was obtained. The patients were followed up for an average period of 50 3. RESULTS months. Local recurrence arose in 10 patients (42%) at a me- dian time of 14 months (range 5–96 months) following ini- 3.1. Patients tial treatment. One of the two patients with a low-grade su- perficial sarcoma developed local recurrence and 9 of the 22 A total of 36 patients with head and neck soft tissue sarcomas with high- or intermediate-grade sarcomas developed local were seen during the study period, 24 of whom were treated recurrence. Local recurrence was strongly related to margins at this unit. This is approximately 2% of the total 1912 cases achieved, arising in six of the ten with an intralesional mar- of all soft tissue sarcomas seen at this unit during the same gin (60%), three of the nine with a marginal margin (33%), period. The median age of the patients was 46 years with a and one of the five with a wide margin (20%). range from 16 to 83 years. There were 24 male and 12 female Of the ten patients who developed local recurrence, four patients (M : F = 2:1). were either known to have systemic metastases already or Thirty-five of the sarcomas were located in the neck were found to have synchronous metastases at the time of and one was located in the scalp. The average duration of restaging. All four received palliative treatment and all died symptoms experienced by patients prior to diagnosis was 54 at a median of 9 months from diagnosis of the local recur- weeks (range 1–416 weeks) and the most commonly reported rence. Six patients with local recurrence had no evidence symptom was the presence of a painless lump. of metastases when they developed the local recurrence and The rest of the observations and analysis are based on the were treated aggressively with further surgical excision and 24 patients who received treatment at this unit. We have ex- radiotherapy when possible, often requiring extensive surgi- cluded 12 patients who were either referred for advice only cal reconstructions in order to obtain wide margins of exci- (9 patients) and received definitive treatment elsewhere or sion. Two of these patients subsequently developed metas- who presented with local recurrence and/or metastases after tases 6 and 12 months later, respectively, and both subse- previous failed treatment (3 patients). Various observations quently died. The other four patients remained disease-free on tumours, treatment, local control, and outcome are sum- at a mean of 52 months following their local recurrence. marised in Table 1. 3.5. Metastases 3.2. Tumours The median tumour size was 5.5 cm (range 0.6–13 cm) at di- Ten patients (42%) developed metastatic disease at a median agnosis. 18 of the sarcomas (75%) were deep to the investing time of 17 months (range 0–139 months). Eight patients de- fascia, the rest superficial to the fascia. Two of the sarcomas veloped lung metastases and two lymph node metastases. All were low grade (18%), the rest intermediate (42%, n = 10) or of the patients with concomitant or previous local recurrence high grades (50%, n = 12). All tumours which were located subsequently died as did two of the others without local re- deep to the fascia were of high or intermediate grade. Only currence. Two patients underwent surgical resection of lung one patient (with a Ewing’s sarcoma) had lung metastases at metastases and remained alive and disease-free at a median the time of presentation. of 17 months. Rabindra P. Singh et al. 3 Table 1: Patient age, tumour factors, treatment, local recurrence, and outcome. MPNST: malignant peripheral nerve sheath tumour, DFSP: dermatofibrosarcoma protuberans, MFH: malignant fibrous histiocytoma, SEF: sclerosing epithelioid fibrosarcoma, CT: chemotherapy, RT: radiotherapy. Local Case Age Size Surgical Outcome Diagnosis Depth Definitive treatment Trojani grade recurrence no. (yrs) (cm) margin (months) (months) Leiomyosarcoma Subcutaneous Excision 138 0.6 High Wide Alive, 45 Ewing’s sarcoma Deep CT + excision 222 1.5 High Wide Alive, 208 DFSP Subcutaneous Excision 341 1.7 Intermediate Marginal Alive, 20 DFSP Subcutaneous Excision 424 2 Low Wide Alive, 37 MPNST Subcutaneous Excision 519 3 Intermediate Wide Alive, 36 Ewing’s sarcoma Deep CT + excision + RT 620 4 High Intralesional Alive, 74 Spindle cell sarcoma Deep Excision 741 4 Intermediate Intralesional 8 Alive, 21 864 Spindle cell sarcoma 4 Deep Intermediate Excision + RT Marginal 16 Died, 33 939 MPNST 5 Deep High Excision + RT Intralesional 26 Died, 52 10 53 SEF 5 Deep Intermediate Excision Wide 49 Alive, 139 11 62 Myxoid chondrosarcoma 5 Deep Intermediate Excision Marginal 96 Alive, 157 12 77 MFH 6 Deep High Excision + RT Intralesional 5 Died, 22 13 54 Myxofiibrosarcoma 6.5 Deep High Excision + RT Marginal Alive, 14 14 22 Synovial sarcoma 7 Deep High Excision + RT Intralesional Alive, 35 15 38 MPNST 7 Deep High Excision + RT Intralesional Died, 14 16 50 MPNST 7 Deep Intermediate Excision + RT Marginal Alive, 191 17 65 Liposarcoma 7 Deep High Excision + RT Intralesional 12 Died, 16 18 32 MPNST 8 Deep Intermediate Excision + RT Marginal Alive, 13 19 68 Spindle cell sarcoma 9 Subcutaneous High Excision + RT Wide Alive, 12 20 73 Liposarcoma 9 Deep High Excision + RT Intralesional 41 Died, 51 21 30 Ewing’s sarcoma 10 Deep High CT + excision + RT Intralesional 12 Died, 14 22 48 Synovial sarcoma 10 Deep Intermediate Excision + RT Marginal Alive, 11 23 65 MPNST 10 Deep Intermediate Excision + RT Marginal Died, 45 24 33 Liposarcoma 13 Subcutaneous Low Excision Marginal 8 Alive, 51 Table 2: Histological subtypes. MPNST: malignant peripheral confidence limits (plus or minus 13%) (Figure 1). We inves- nerve sheath tumour, DFSP: dermatofibrosarcoma protuberans, tigated the following factors for possible significance on sur- MFH: malignant fibrous histiocytoma, SEF: sclerosing epithelioid vival. fibrosarcoma. (i) Size. Only 1 patient with a primary sarcoma >5cm has Subtypes No. of patients (%) yet survived more than 5 years whilst the survival for MPNST 6 (25%) patients with tumours ≤5 cm was 71% at 5 years (p = Ewing’s sarcoma 3 (13%) 0.02) (Figure 2). Liposarcoma 3 (13%) (ii) Grade. Neither of the two patients with low-grade tu- mours died but 8 of the 22 with high- or intermediate- Spindle cell sarcoma 3 (13%) grade tumours died (P = .29) (chi-square). Synovial sarcoma 2 (8%) (iii) Depth. None of the 6 patients with subcutaneous sar- DFSP 2 (8%) comas died but 8 of the 18 with deep tumours died Myxofibrosarcoma 1 (4%) (P = .0455) (chi-square). Leiomyosarcoma 1 (4%) (iv) Margin. Six of the 10 patients with intralesional and MFH 1 (4%) two of the 9 patients with a marginal surgical margin Myxoid Chondrosarcoma 1 (4%) died, however none of the 5 patients with a wide sur- SEF 1 (4%) gical margin died (P = .04). (v) Age. We could find no effect of age on survival. Combining these factors revealed that all deaths arose in 3.6. Survival the patients with high- or intermediate-grade deep tumours. Eight patients died at a median time of 2.3 years from diag- When further stratified by size, this showed that two of the nosis. Overall survival was 48.6% at five years but with wide seven patients with high-grade deep tumours ≤5 cm died 4 Sarcoma Our unit is a musculoskeletal unit that takes referrals of pa- tients with both proven or suspected sarcomas. In the case of the head and neck tumours, some were referred directly to us 0.8 for investigation and diagnosis whilst others were referred af- ter a biopsy or imaging had confirmed the diagnosis of a sar- 0.6 coma. We treated patients with sarcomas that were confined to the superficial tissues or deep muscles of the head and neck 0.4 and we have not included patients with soft tissue sarcomas involving the facial skeleton or the oropharynx which pose 0.2 even greater challenges in treatment [6]. Our management policy was based on principles used in treating soft tissue sarcomas at other sites. The head and neck 0 2 4 6 8 1012 14 1618 poses particular problems however because of the proxim- Time (years) ity of so many important structures and the near impossibil- ity of obtaining wide surgical margins in many cases. Unlike Figure 1: Overall 5-year survival. limb soft tissue sarcomas, there is no fallback option of doing an amputation if local recurrence arises. The local recurrence rates for high-grade soft tissue sar- comas after surgical excision have been reported to be as high as 50% in the literature [3, 9, 10]. 42% of patients developed 0.8 Up to 5 cm local recurrence in our study, most arising within 2 years of treatment. Barker et al. in their study reported the median 0.6 time to local recurrence after treatment with surgery and/or radiotherapy to be 4 months, and Kraus et al. reported that 0.4 patients who developed local recurrence did so within 3 years [11, 12]. Over 5 cm 0.2 The risk of local recurrence was higher with intralesional or marginal surgical margins as has been shown by other au- p = 0.02 thors [2, 12]. In view of this, every effort should be made to maximise the margins that can be achieved at the time of the 0 2 4 6 8 1012 14 1618 first surgical procedure, if necessary by going back and doing Time (years) a further wide excision if the initial margins prove positive. Figure 2: Overall survival by size of sarcoma. All patients should have their case discussed at a multidisci- plinary team meeting and the option of radiotherapy consid- ered to try and decrease the risk of local recurrence. Even if patients do develop local recurrence, their case is not hope- compared with 6 of the 11 with high-grade deep tumours less and further excision should be considered. Clearly, how- >5cm (P = .04). ever, initial wide surgical margins should always be aimed for. The commonest site for metastases was the lungs which 4. DISCUSSION was also the commonest cause of death. Mendenhall et al. [3] suggested that patients should undergo a chest CT be- Head and neck sarcomas are rare and the paucity of stud- fore treatment and also suggested that in the absence of pul- ies about their management and outcome testifies to this. monary metastases, other distant metastases are highly un- Head and neck lumps are common and have a variety of likely. We concur with this. diagnoses [2, 3]. Early detection and diagnosis is clearly es- The5-yearsurvivalrateof49% in ourstudy (Figure 1)is sential. The National Institute for Health and Clinical Excel- comparable to a previous UK study by Eeles et al. [4]based lence (NICE) guidance 2005 to all UK general practitioners at the Royal Marsden Hospital of London. They analysed 103 emphasises that “In patients with an unexplained lump in the cases seen over 44 years between 1944 and 1988 and reported neck which has recently appeared or a lump which has not been 50% overall 5-year survival rate. This is similar to the results diagnosed before that has changed over a period of 3 to 6 weeks, reported by Bentz et al. [6] from Memorial Sloan Kettering an urgent referral should be made” [8]. Whilst more general Cancer Centre. Most authors agree that the same prognostic advice is also given about lumps elsewhere in the body: “In factors apply to sarcomas no matter where they arise—grade, patients presenting with a palpable lump, an urgent referral for size, and depth. In the head and neck, however, local recur- suspicion of soft tissue sarcoma should be made if the lump is rence has more sinister portents because of the difficulty of (i) greater than about 5 cm in diameter, subsequent management [5, 13–18]. (ii) deep to fascia, fixed, or immobile, Obtaining local control is paramount in managing these (iii) painful, head and neck sarcomas. Obtaining wide margins may of- (iv) increasing in size, ten require a multidisciplinary team consisting of a sar- (v) a recurrence after previous excision.” coma surgeon, a head and neck surgeon and a reconstructive Cum. survival Cum. survival Rabindra P. Singh et al. 5 surgeon. A clinical oncologist is an essential part of the team prospective series,” World Journal of Surgery,vol. 27, no.7,pp. 875–883, 2003. to advise about radiotherapy usage. A metaanalysis pub- [11] J. L. Barker Jr., A. C. Paulino, S. Feeney, T. McCulloch, and lished in Lancet revealed that chemotherapy did not pro- H. Hoffman, “Locoregional treatment for adult soft tissue sar- duce a survival benefit in the treatment of soft tissue sarco- comas of the head and neck: an institutional review,” Cancer, mas [19]. The same analysis did, however, show a 10% ben- vol. 9, no. 1, pp. 49–57, 2003. efit of chemotherapy on recurrence-free survival. Adjuvant [12] D. H. Kraus, S. Dubner, L. B. Harrison, et al., “Prognostic fac- chemotherapy is not usually advocated for localised soft tis- tors for recurrence and survival in head and neck soft tissue sue sarcomas but can be considered for metastatic disease as sarcomas,” Cancer, vol. 74, no. 2, pp. 697–702, 1994. a palliative treatment. 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Irish, et al., “Preoperative radio- therapy for adult head and neck soft tissue sarcoma: assess- ment of wound complication rates and cancer outcome in a MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 International Journal of Journal of Immunology Research Endocrinology Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Submit your manuscripts at http://www.hindawi.com BioMed PPAR Research Research International Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Research and Treatment Cellular Longevity Neurology Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014

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