CLINICAL REVIEW ADULT HEAD AND NECK SOFT TISSUE SARCOMAS
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1 CLINICAL REVIEW Mark K. Wax, MD, Section Editor ADULT HEAD AND NECK SOFT TISSUE SARCOMAS William M. Mendenhall, MD, 1 Charles M. Mendenhall, MD, 2 John W. Werning, MD, 3 Charles E. Riggs, MD, 4 Nancy Price Mendenhall, MD 1 1 Department of Radiation Oncology, University of Florida College of Medicine, P. O. Box , Gainesville, FL mendewil@shands.ufl.edu 2 Department of Radiation Oncology, Phoebe Putney Memorial Hospital, Albany, Georgia 3 Department of Otolaryngology, University of Florida College of Medicine, Gainesville, Florida 4 Division of Medical Oncology, University of Florida College of Medicine, Gainesville, Florida Accepted 24 March 2005 Published online 31 August 2005 in Wiley InterScience ( DOI: /hed Abstract: Background. The purpose was to determine the optimal treatment for adult patients with head and neck soft tissue sarcomas. Methods. We conducted a review of the pertinent literature. Results. Local control after surgery alone or combined with radiotherapy was obtained in approximately 60% to 70% of the patients. The probability of local control is influenced by histologic grade, tumor size, and surgical margins. Patients with high-grade tumors and/or positive margins have improved local control if adjuvant radiotherapy is used. Distant metastases occurred in 10% to 30% of patients. The 5-year overall and cause-specific survival rates varied from approximately 60% to 70% and are affected by age, histologic grade, previous treatment of tumor, invasion of deep structures, and adequacy of surgery. Conclusions. The optimal treatment for adult head and neck soft tissue sarcomas is surgery. Adjuvant radiotherapy improves outcomes for those with high-grade tumors and/or positive margins. Radiotherapy alone will cure a small subset of patients with unresectable tumors. A 2005 Wiley Periodicals, Inc. Head Neck 27: , 2005 Keywords: adult; soft tissue sarcoma; radiotherapy; distant metastases; treatment outcomes Correspondence to: W. M. Mendenhall B 2005 Wiley Periodicals, Inc. Soft tissue sarcomas arising in the head and neck of adults are rare. They account for approximately 10% of all soft tissue sarcomas and approximately 1% of head and neck tumors. 1,2 Kraus et al 3 reported that 60 of 1400 patients (4%) treated at the Memorial Sloan Kettering Cancer Center for soft tissue sarcomas between 1982 and 1989 had tumors arising in the head and neck. There is a variable male preponderance; the median age is approximately 50 to 55 years with a wide range (Table 1). A small subset of tumors occur in sites that have been previously irradiated. 2 Two of 60 patients (3%) reported by Kraus et al 3 had a history of previous radiotherapy (RT). Most patients are initially seen with a painless mass. 4 Thirty-nine of 57 patients (68%) reported by Willers et al 1 had a painless mass; the median interval between onset and diagnosis was 5.5 months (range, 0 35 months). Dijkstra et al, 5 from The Netherlands Cancer Institute, observed that 55 of 58 patients (95%) had a painless mass that had been present on average for 11 months (range, 1 60 months). The most common primary sites are the scalp, face, and neck (Table 1). Barker et al 6 observed 916 Adult Head and Neck Soft Tissue Sarcoma
2 Table 1. Patient demographics. Parameter Series Institution MGH 1 U. Iowa 6 TMH 25 MSKCC 3 PHM 24 UCSF 23 U. Illinois 26 NCI 5 Study date No. of patients Mean age, y Age range, y Male/female ratio 2.8: : : : : : :1.0 Site, % Scalp Face Neck Orbit Nasal cavity/sinuses Oral cavity Larynx/pharynx Other Histologic grade, % Low Intermediate High No data 3 Maximum diameter, % V5 cm >5 cm No data Histologic subtypes MFH Angiosarcoma Neurogenic sarcoma* DFSP Fibrosarcoma Leiomyosarcoma Synovial sarcoma Liposarcoma Epithelioid sarcoma 2 2 Sarcoma (NOS) Desmoid 3 8 Other Abbreviations: MGH, Massachusetts General Hospital; TMH, Tata Memorial Hospital; MSKCC, Memorial Sloan-Kettering Cancer Center; PMH, Princess Margaret Hospital; UCSF, University of California, San Francisco; NCI, Netherlands Cancer Institute; MFH, malignant fibrous histiocytoma; DFSP, dermatofibrosarcoma protuberans; NOS, Not otherwise specified. *Neurogenic sarcomas include malignant schwannoma and malignant peripheral nerve sheath tumor. that 22 of 44 patients (50%) treated at the University of Iowa had relatively superficial tumors, whereas the remainder involved deeper structures. Most head and neck soft tissue sarcomas are high grade (Table 1). A wide spectrum of histologic subtypes is observed; the prognosis may vary depending on the histologic findings (Table 1). Most authors exclude patients with embryonal rhabdomyosarcomas and extraosseous Ewing s sarcomas, because the natural history is different from most other soft tissue sarcomas. 7 Some authors also exclude patients with angiosarcomas, because the prognosis is significantly worse compared with other soft tissue sarcomas. 1,8 Desmoid tumors, also called aggressive fibromatosis, are locally aggressive benign tumors that have a favorable prognosis and are usually excluded. 9 Although dermatofibrosarcoma protuberans may metastasize, it is a lowgrade lesion that is sometimes excluded because of its more favorable outcome (Table 1). 10 For the remainder, histologic grade has more of an impact on outcome than histology. DIAGNOSTIC EVALUATION CT and/or MRI are used to evaluate the extent of the primary lesion and to assess the regional lymph nodes. The likelihood of regional lymph node metastases is low. One of 44 patients (2%) Adult Head and Neck Soft Tissue Sarcoma 917
3 reported by Barker et al 6 had a positive regional node at presentation. Three of 60 patients (5%) reported by Kraus et al 3 experienced regional lymph node recurrences after treatment; one of three also had a local recurrence. Fine-needle aspiration (FNA) is the first step to obtaining a histologic diagnosis of a neck mass. 2 However, the sample is limited and may not be diagnostic, in which case a core needle biopsy or limited incisional biopsy may be necessary. 2 Soft tissue sarcomas are prone to seeding, and care should be taken not to contaminate a potential future operative site. The likelihood of distant metastases is related to histologic grade and tumor size; the risk is highest for large, high-grade lesions. 11 The most common site for distant metastases is the lung. Thus, patients should undergo a chest CT before treatment. Metastases to other sites are unlikely, particularly in the absence of pulmonary metastases, so that additional diagnostic studies, such as a brain MRI or a bone scan, are not necessary in the absence of symptoms. Although the utility of positron emission tomography (PET) is ill defined for soft tissue sarcomas, it may be useful, particularly if one or more pulmonary nodules of unclear significance are appreciated on CT. STAGING Disease is staged according to the American Joint Committee on Cancer (AJCC) 12 staging system (Table 2). TREATMENT The optimal treatment is complete resection. Postoperative adjuvant RT is indicated for patients with low-grade tumors who have close (<1 cm) or positive margins, as well as those with high-grade tumors. 2 Although radical resection alone results in a high rate of local control, achieving a complete compartmental resection in the head and neck is usually not feasible. At best, wide margins may be achieved, and the recurrence rates for high-grade soft tissue sarcomas after a wide local excision may be as high as 50% Thus, most patients receive adjuvant RT, including those with low-grade lesions. Patients with marginally resectable or incompletely resectable tumors are treated initially with RT. If the lesion is likely to be resectable, the dose is 50 Gy administered once or twice daily over approximately 5 weeks, followed by surgery Table 2. Definition of TNM. 12 TNM Definition Primary tumor (T)* TX Primary tumor cannot be assessed T0 No evidence of primary tumor T1 Tumor V5 cm in greatest dimension T1a Superficial tumor T1b Deep tumor T2 Tumor >5 cm in greatest dimension T2a Superficial tumor T2b Deep tumor Regional lymph nodes (N) NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1y Regional lymph node metastasis Distant metastasis (M) MX Distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis *Note: Superficial tumor is located exclusively above the superficial fascia without invasion of the fascia; deep tumor is located either exclusively beneath the superficial fascia, superficial to the fascia with invasion of or through the fascia, or both superficial yet beneath the fascia. ynote: Presence of positive nodes (N1) is considered stage IV. 4 to 6 weeks later. 16,17 An advantage of preoperative RT is that the risk of late complications may be reduced because a lower dose is used. This is particularly relevant when treating tumors involving the skull base in close proximity to the eyes and optic nerves. If surgery is not feasible, the tumor is treated with definitive RT to a high dose ( Gy at 1.2 Gy per fraction twice daily in a continuous course). 11,16 It is difficult to assess the efficacy of RT alone, because it is usually used for large unresectable tumors that have a low chance of cure after any treatment modality. However, it is likely that surgery and RT are more efficacious than RT alone for resectable tumors. In the event that high-dose RT is necessary, the use of intensity-modulated RT (IMRT) or proton beam RT may be used to reduce the risk of late complications in patients in whom the tumor is close to dose-limiting normal tissues. The value of adjuvant chemotherapy is unclear. Few data directly pertain to the efficacy of adjuvant chemotherapy for head and neck soft tissue sarcomas, so that it is necessary to extrapolate data from soft tissue sarcomas arising in more common locations A recent metaanalysis has shown that doxorubicin-based adjuvant chemotherapy significantly improves both local control and distant metastases free survival, particularly for patients with extremity sarcomas. 22 Although relapse-free survival was also 918 Adult Head and Neck Soft Tissue Sarcoma
4 significantly improved, the improvement in overall survival was not statistically significant. 22 However, subset analysis of patients with extremity soft tissue sarcomas revealed a significant improvement in overall survival for patients who received adjuvant chemotherapy. 22 Frustaci et al 20 reported on 104 adult patients with highgrade soft tissue sarcomas of the extremities and girdles who were randomly assigned to surgery with or without adjuvant RT alone or combined with five cycles of adjuvant ifosfamide and 4Vepidoxorubicin. Patients who received adjuvant chemotherapy had a significant improvement in both disease-free survival ( p =.04) and overall survival ( p =.03). However, the rates of distant metastases were essentially the same in both treatment groups, so that the survival advantage for those who received chemotherapy will likely disappear with longer follow-up. OUTCOMES The results of treatment with various combinations of surgery and RT are depicted in Table 3. The 5-year local control rates range from approximately 60% to 70%, which are similar to the 5-year cause-specific and overall survival rates. In contrast, the local control rate after limb-sparing surgery and adjuvant RT for extremity soft tissue sarcomas is approximately 90% and is probably related to the ability to obtain wider margins than with head and neck neoplasms. 16 Approximately 10% to 30% of patients will experience distant metastasis. Patients who experience recurrence after treatment will usually do so within 2 years. Barker et al 6 observed that the median time to development of a local recurrence after surgery and/or RT was 4 months (range, 1 28 months). 6 Kraus et al 3 reported that 23 of 24 patients (96%) who experienced a recurrence after treatment did so within 3 years. Thus, 5-year outcomes data may be considered mature. Patients who experience a recurrence after treatment may sometimes be salvaged, depending on the extent and location of the disease. Barker et al 6 reported that 14 of 19 patients (74%) who experienced a locoregional recurrence underwent a salvage attempt and that nine patients (47%) were rendered disease free. Successful salvage procedures included surgery alone (five patients), RT alone (three patients), and surgery and postoperative RT (one patient). One of three patients salvaged with RT alone had been previously irradiated. Table 3. Treament and outcomes. Institution MGH 1 U. Iowa 6 TMH 25 MSKCC 3 PMH 24 UCSF 23 U. Illinois 26 NCI 5 PHM 17 Study dates No. of patients * 40 Follow-up Median, 4.3 y Median, 4.8 y Minimum, 3 y Median, 5.3 y Mean, 3.6 y Previously untreated, % Treatment Surgery 66% 47% 52% 19% 22% 19% Surgery + radiotherapy 77% 25% 53% 48% 81% 61% 60% 100% Radiotherapy 23% 9% 17% 21% Adjuvant chemotherapy 12% 6% 2% 23% 22% 5% Outcomes percent (interval) Local control 60% (5 y) 57% (5 y) 63%y 70% (5 y) 59% (5 y) 66% (5 y) 72%y 80% (2 y) DMFS 77 (5 y) 90%y 87%y 69% (5 y) 86%z 85% (5 y) DFS 45% (5 y) 60% (5 y) 54% (5 y) 52% (5 y) CSS 72% (5 y) 62% (5 y) 60% (5 y) OS 66% (5 y) 61% (5 y) 60% (5 y) 71% (5 y) 56% (5 y) 60% (5 y) Abbreviations: MGH, Massachusetts General Hospital; TMH, Tata Memorial Hospital; MSKCC, Memorial Sloan-Kettering Cancer Center; PMH, Princess Margaret Hospital; UCSF, University of California San Francisco; NCI, Netherlands Cancer Institute; DMFS, distant metastasis free survival; DFS, disease-free survival; CSS, cause-specific survival; OS, overall survival. *Four of 60 patients with distant metastases. ycrude numbers. zincludes regional metastases. Adult Head and Neck Soft Tissue Sarcoma 919
5 Table 4. Prognostic factors and results of multivariate analyses. Series Institution MGH 1 U. Iowa 6 TMH 25 MSKCC 3 UCSF 23 NCI 5 Study dates No. of patients Local control T stage (p =.05), Freedom from distant metastases treatment group (p =.09) Direct extension to deep structures or skin (p =.007). Extent of surgery (p =.03) Margin status (p =.001) Histologic grade (p =.01); tumor size (p =.004) Cause-specific survival Age (p =.009); histologic grade (p =.0002); inadequate surgery (p =.008); surgical margins (p =.0009) Overall survival Histologic grade (p =.001); previously untreated vs recurrent (p =.017); direct extension (p =.034); age (p =.059) Age (p =.03), AJCC stage (p =.05) Histologic grade p = (.001); tumor size (p =.04) Margin status (p =.01); histologic grade (p =.03) Age (p <.0001); histologic grade (p <.0001); distant metastases at diagnosis (p <.0001); deep vs superficial primary site (p =.0003), previously untreated vs recurrent disease at presentation (p =.022) Abbreviations: MGH, Massachusetts General Hospital; TMH, Tata Memorial Hospital; MSKCC, Memorial Sloan-Kettering Cancer Center; UCSF, University of California San Francisco; NCI, Netherlands Cancer Institute. 920 Adult Head and Neck Soft Tissue Sarcoma
6 Prognostic Factors. The impact of various prognostic factors on outcome as assessed by multivariate analyses are summarized in Table 4. In general, outcomes are better for young patients with small, superficial, previously untreated, lowgrade tumors that have been resected with negative margins. Le et al 23 reported on 65 patients treated with surgery and/or RT and observed the following 5-year local control rates: T1 versus T2 tumors (92% vs 40%, p =.004) and grade 1 to 2 versus grade 3 to 4 tumors (80% vs 48%, p =.01). Although it is desirable to obtain negative margins, it is difficult to evaluate the impact of margin status because of selection bias. Patients with larger tumors invading deep structures are more likely to have an unfavorable outcome, and the tumor is also less likely to be completely resectable. Le Vay et al 24 reported the following local control rates in a series of 52 patients treated with surgery alone or combined with adjuvant RT: negative margins, 74%; microscopically positive margins, 70%; and gross residual disease, 25%. Similarly, it is difficult to assess the efficacy of adjuvant RT, because patients with favorable, completely resectable tumors tend to be appropriately treated with surgery alone, whereas those with unfavorable and/or incompletely resected tumors tend to receive adjuvant RT. 4 Le et al 23 observed the following 5-year local control rates: surgery, 59%; surgery and RT, 77%; and RT alone, 0%. Barker et al 6 reported on four patients treated with RT alone; two of four were locally controlled. Willers et al 1 reported on 46 patients treated for soft tissues sarcomas (excluding angiosarcomas) with RT alone or combined with surgery and found that those who had a gross total resection and RT had improved local control compared with those who were treated with subtotal resection and RT or RT alone ( p =.088). Complications. The likelihood of complications depends on the site and extent of the tumor and the treatment that is used. In addition, patients in relatively poor health are probably more likely to experience complications. Willers et al 1 reported that one of 46 patients (2%) treated with RT alone or combined with surgery experienced a severe complication that consisted of a necrosis that eventually healed with conservative management. O Sullivan et al 17 reported that eight of 40 patients (20%) treated on a prospective study with preoperative RT (50 Gy in 25 fractions over 5 weeks) and surgery experienced major wound complications after surgery, defined as secondary wound surgery (three patients), readmission or prolonged hospitalization for wound care (two patients), prolonged dressing changes (two patients), and invasive procedure for wound care (one patient). Because almost all the complications data that are reported have been analyzed retrospectively, it is likely that the incidence of complications is underreported. CONCLUSIONS The optimal treatment for adults with head and neck soft tissue sarcomas is complete resection. Adjuvant RT likely improves the probability of cure in patients with high-grade tumors and those with close or positive margins. RT alone may cure a small subset of patients with advanced unresectable lesions. Although the efficacy of adjuvant chemotherapy is ill defined, it should be considered for patients with high-grade lesions. REFERENCES 1. Willers H, Hug EB, Spiro IJ, Efird JT, Rosenberg AE, Wang CC. Adult soft tissue sarcomas of the head and neck treated by radiation and surgery or radiation alone: patterns of failure and prognostic factors. Int J Radiat Oncol Biol Phys 1995;33: Balm AJ, Vom Coevorden F, Bos KE, et al. Report of a symposium on diagnosis and treatment of adult soft tissue sarcomas in the head and neck. Eur J Surg Oncol 1995;21: Kraus DH, Dubner S, Harrison LB, et al. Prognostic factors for recurrence and survival in head and neck soft tissue sarcomas. Cancer 1994;74: Weber RS, Benjamin RS, Peters LJ, Ro JY, Achon O, Goepfert H. Soft tissue sarcomas of the head and neck in adolescents and adults. Am J Surg 1986;152: Dijkstra MD, Balm AJM, van Coevorden F, et al. Survival of adult patients with head and neck soft tissue sarcomas. 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