HEAD AND NECK SARCOMA: REPORT OF THE HEAD AND NECK SARCOMA REGISTRY Society of Head and Neck Surgeons Committee on Research: Harold J. Wanebo, MD, R. James Koness, MD, John K. MacFarlane, MD, Frederick R. Eilber, MD, Robert M. Byers, MD, E. George Elias, MD, and Ronald H. Spiro, MD
A Head and Neck Sarcoma Registry was established by the Society of Head and Neck Surgeons to review treatment results of a rare tumor by surgeons with special interest in this anatomic site. Two hundred fourteen patients were analyzed. There were 194 adult tumors and 20 pediatric tumors. The major sites included parotid and neck, 20%; face and forehead, 18%; maxilla and palate, 13%; scalp, 12%; mandible, 11%; paranasal sinuses, 7%; larynx, 2%; and oral cavity, 5%. Eighty-four percent were resectable. The disease-free survival was 56%; overall survival was 70% at 5 years. Major determinants of suwival were adequacy of resection (margins free of tumor) and tumor type. Survival differed according to tumor cell type (tumor grade was not available). Patients with chondrosarcoma and dermatofibrosarcoma had survival approaching 100%. Patients with malignant fibrous histiocytoma (MFH) and fibrosarcoma (FSA) had intermediate survival of 60% to 70%. The worst survival, < 50% at 5 years, occurred in patients with osteosarcoma, angiosarcoma, and rhabdomyosarcoma in decreasing order. This
From the Society of Head and Neck Surgeons, Committee on Research: Department of Surgical Oncology (Drs. Wanebo and Koness), Brown University, Providence, Rhode Island; Department of Surgery (Dr. MacFarlane), St. Paul's Hospital, Vancouver, British Columbia, Canada; University of California at Los Angeles (Dr. Eilber), Los Angeles, California; Houston, Texas (Dr. Byers); Department of Oncology (Dr. Elias), University of Maryland Hospital, Baltimore, Maryland; and Memorial Hospital (Dr. Spiro), New York, New York. Address reprint requests to Dr. Harold J. Wanebo, Roger Williams Medical Center, 825 Chalkstone Avenue, Providence, RI 02908, Accepted for publication July 30, 1991. CCC 0148-6403/92/0101-07$04.00 Q 1992 John Wiley & Sons, Inc.
Head and Neck Sarcoma Registry
suggests a rationale for identifying high-risk patients for prospective adjuvant protocols. This study emphasizes the value of recording uncommon tumors to provide relevant information for future study and possibly therapy. HEAD & NECK 1992:14:1-7
Sarcomas of the head and neck are rare tumors, constituting approximately 15% of all sarcomas, but less than 1%of tumors in this region.lW7Sarcomas are biologically diverse depending on In their type, grade, and site of addition, biologic differences exist in pediatric versus adult sarcomas and in their response to treatment by surgery and adjuvant therapy.11-13 Because of their diversity and their biologic complexity, a Head and Neck Sarcoma Registry was established by the Society of Head and Neck Surgeons to record the number of patients with primary soft-tissue and bone tumors who are being managed by a group of surgeons devoted to the practice of head and neck surgery. The purpose of this registry is to classify these lesions and to correlate the results with other series, as well as to establish an ongoing registry from which new information could be developed, possibly leading to development of clinical trials for specific tumor subtypes. The registry was begun in 1986 with the mailing out of protocols to active mem-
HEAD & NECK
JanuarylFebruary 1992
1
bers of the Society. The results and a retrospective data analysis of the initial 214 patients treated from 1982 to 1990 are reported and discussed. METHODS AND MATERIALS
The records of 214 patients with primary sarcomas of the head and neck that were being managed by individual surgeons or surgical groups from 33 institutions were recorded on a protocol form that was sent to the central office. Each form was reviewed by the project coordinator and entered onto the computer. The original tumor type and grade were recorded by the contributing institution. The basic categories in the protocol included patient initials, age, sex, time of diagnosis, the primary tumor site, the tumor cell type and grade, the initial primary treatment, adjuvant therapy, if any, and follow-up results. The registry asked participating surgeons to provide periodic status reports on patients who were entered. Excluded from analysis were patients with dural or intracranial extradural tumors and those with tumors of nonmesodermal origin or originating from blood-forming organs. Sites included were tumors of the face, neck, parotid and ear, nares and paranasal sinuses, neck, scalp, oral cavity, pharynx, larynx, hypopharynx and ear. The pediatric group included persons < 18 years of age. The analysis was done on a PC computer using an SAS program for statistical analysis. Survival curves were generated by the KaplanMeier method.14 Statistical anaylsis was performed using the log rank or Gehan-Wilcoxon technique and the Cox proportional-hazards model. RESULTS
Data sheets on 214 patients were returned. This included 194 adults and 20 pediatric patient tumors; 38% were female and 62% were male. The median age was 45 years (range, 1-86 years). The age categories included < 18 years, 20 patients; 18-40 years, 74 patients; 41-60 years, 46 patients; and > 60 years, 74 patients. Eightyone percent had soft-tissue tumors and 19%had bone tumors. The presenting symptoms included a mass lesion in 85 patients (49%),pain in 61 patients (35%), and skin change in 25 patients (14%).No presenting symptoms were recorded in 43 patients. The most common tumor types are listed in Table 1. These include angiosarcoma, 31 pa-
2
Head and Neck Sarcoma Registry
TABLE 1. Head and neck sarcoma registry: tumor types.* Grade ~
-~
~
Primary
Recurrent
27 15
2 -
20 14
-
8
2
11 4
-
~~
High-intermediate grade Bone Osteosarcoma Chondrosarcoma Fibrous MFH Fibrosarcoma Smooth muscle Leiomyosarcoma Skeletal muscle Rhabdomyosarcoma Emb rhabdomyosarcoma Vascular Ang iosarcoma Hemangiopericytoma Fatty Liposarcoma Neural Malignant schwannoma Neurofrbrosarcoma Unclassified Other Low-grade tumors Dermatofibrosarcoma protuberans Desmoid tumors Other spindle cell sarcomas Total
3
-
29 6
-
4
-
7
1 2
2 12 10 11 4 5 189
2
-
1 1 -
14
'Cases eliminated from ana/ysis lymphoma 6 , Kaposi's 2, metastatic sarcoma, 2, ameboblastic fibroma, 1
tients; fibrosarcoma, 20 patients; malignant fibrous histiocytoma, 20 patients; osteosarcoma, 29 patients; chondrosarcoma, 15 patients; rhabdomyosarcoma, 11 patients; and embryonal rhabdomyosarcoma, 4 patients. Twelve tumors were unclassified and 2 were stated to be metastatic. Only a small number of tumors were graded (< 20 patients). Eliminated from analysis were lymphoma, 6 patients; Kaposi's, 2 patients; metastatic sarcoma, 2 patients; and ameloblastic fibroma, 1 patient. Sixty patients had tumors involving the neck or parotid area (28%);38 had face and forehead tumors; 28 had involvement of the maxilla and alveolus; 25 had sarcomas of the scalp; and 24 had mandibular involvement. The remaining sites included paranasal sinuses, 16 patients; soft tissue of oral cavity and pharynx, 10 patients; larynx, 5 patients; while in 8 patients the site was not recorded. Tumor size was < 3 cm in 33 patients; 3-5 cm in 64 patients; > 5 cm in 41 patients; and size was not stated in 76 patients. The median tumor size recorded was 4.0 cm.
HEAD & NECK
JanuaryiFebruary 1992
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FIGURE 1. Kaplan-Meier curves showing the estimated overall survival of 203 patients operated on for primary sarcoma of the head and neck. The mean survival at 5 years was 70%, and at 10 years it was 55%.
FIGURE 3. The overall survival according to size < 3 cm versus > 3 cm or 75 cm showed no significant difference (KaplanMeier plot with Gehan-Wilcoxon determination of significance).
TREATMENT
ease-free survival was 75 months with a 57% disease-free 5-year survival. The relationship of survival according to tumor size is shown in Figure 3. The survival was 84% in patients with tumors < 3 cm compared to 57% and 63% in patients with tumors 3-5 cm or > 5 cm, but these differences were not significant (p = 0.3). The pediatric patients had a 86% survival at 60 months compared to 68% survival in adults (p = 0.1) (Figure 4). The relationship of survival to tumor and type is listed in Figure 5. Bone and soft-tissue survival curves were nearly identical. Patients with dermatofibrosarcoma and chondrosarcoma had excellent survival (approaching loo%), whereas patients with MFH and fibrosarcoma had intermediate survival (60% to 70%). Patients with osteosarcoma, angiosarcoma, and rhabdomyosarcoma had survival < 45% (p < 0.008). Because of the infrequent application of grading, this parameter could not be studied for its survival relationships. Although there was an apparent difference in patients resected for recurrent versus primary sarcomas, this was not
Surgical resection was performed in 179 patients, biopsy only in 24 patients, and ll patients had no surgery. In 163 patients, the resection was done with curative intent (all gross disease removed). The margins were microscopically involved in 27 (17%)of these patients. Wide local excision was performed in 179 patients, and was combined with neck dissection in 15 patients. Other procedures included maxillectomy in 27 patients; mandibulectomy in 20 patients; and orbital exenteration in 5 patients, laryngopharyngectomy in 5 patients. Radiation therapy (RT) was given as an adjuvant to 58 patients; chemotherapy (CT) was given to 31 patients, and combined radiationkhemotherapy (RT/CT) was given to 38 patients. RT and/or CT was given to 46 of 57 patients with involved margins. The overall and disease-free survival curves are shown in Figures 1 and 2. The median survival was 127 months, and the estimated survival at 60 months was 70%. The median dis-
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FIGURE 2. The estimated disease-free survival of 186 patients resected of head and neck sarcoma was 58% and the 10-year disease-free survival was 33% (Kaplan-Meier plot).
Head and Neck Sarcoma Registry
*
I
0
censored 30
60
90
120
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184
MONTHS FROM DX TO DEATH
FIGURE 4. The overall survival of pediatric versus adult patients shows no significant difference.
HEAD & NECK
January/February 1992
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significant ( p = 0.28) (Figure 6). The results of resection as related to margin involvement shows significantly better survival in patients with clear margins compared with those with involved margins ( p = 0.05) (Figure 7). Patients who received adjuvant therapy (chemotherapy and/or radiation) had lower survival rates than those who received no adjuvant therapy ( p = 0.03). Because of the heterogeneity of therapy administered, the biologic importance of this is unclear. In a multivariant analysis, the only independently significant preditors of improved overall survival were pediatric patients and clear margins ( p = 0.01 and p = 0.005, respectively). DISCUSSION
This review of 214 patients from the Head and Neck Sarcoma Registry is one of the largest series reported of sarcomas from this anatomic site
I
i RECURRENT
0
30
60
90
120
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FIGURE 6. There was no significant difference in the estimated overall survival between groups with primary versus recurrent sarcoma (Kaplan-Meier curve, Gehan-Wilcoxon statistic).
4
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and may provide insight into management by surgeons with a committment to head and neck cancers. These tumors are uncommon, considering the rarity of primary sarcomas in the United States (less than 5000 new cases each year) and the infrequency of the head and neck as a primary site for sarcomas (about 15%to 20%). This series epitomizes the biologic and pathologic diversity of sarcomas in this region as reported by other series. Approximately 80% of the tumors originated in soft tissue. The remaining were bone tumors and were approximately evenly divided between osteosarcoma and chondrosarcoma. A relationship of tumor type to site was evident, i.e., angiosarcomas are frequent in the scalp, much less common in other head and neck sites. Fibrosarcoma and malignant fibrohistiocytoma are more common in the parotid and neck and face region, whereas the bone tumors are more common in the maxillafalveolar ridge and mandibular region. Unfortunately, only a small number of these tumors was assigned a grade by the pathologist at the referring institution. Current staging of sarcomas is based on tumor grade; however, it was not applied in most of these cases. Although some of the patients may have predated the time period when grading became established as an essential feature of staging, many of the patients were treated during this time period, but were still not graded by the institutional pathologist for various reasons. This may reflect difficulties in applying grading criteria to these tumors which is a reason for establishing a central sarcoma pathology registry. Only 4 of 7 head and neck sarcoma series collected between 1982 and 1990 were
HEAD & NECK
January/February 1992
primary tumor factors of necrosis, high mitotic count, histiologically undifferentiated tumors, and blood vessel invasion were all related to poor prognosis. Multivariate analysis of the above prognostic factors showed that local recurrence was largely related to the quality of the surgery (ie, wide resection with microscopially clean margins), whereas the occurrence of distant metastases was related to tumor size, margin, presence of tumor necrosis, and the adequacy of excision. This study confirms that the adequacy of the excision is of extreme importance in tumor control, especially if surgery is the primary modality. In this registry, the pediatric patients appeared to do better as a group than the adult patients. Usually these patients present with a more aggressive tumor, largely rhabdomyosarcoma (RMS), and have had severely impaired survival in previous reviews.15-17 About one-third of our pediatric patients had rhabdomyosarcoma. Although the patients with rhabdomyosarcoma did poorly as a group, the pediatric patients did better than the adult patients with this tumor type, possibly because of adjuvant therapy. The Intergroup RMS study has demonstrated an improved prognosis using a multidisciplinary approach,18 although it was subsequently noted that these patients may suffer delayed consequences of combined modality therapy.lg A study of pediatric head and neck tumors by Rao and colleaguesz0 stated that surgery alone may be sufficient initial therapy in the subset of
graded (Table 2). Currently, we are retrieving the slides from individual case contributors for review by a single pathologist experienced in softtissue and bone tumors, to permit a more detailed clinical pathologic review in the future. Survival is directly related to tumor type. Patients with chondrosarcoma have excellent survival, essentially equivalent to that of patients with dermatofibrosarcoma protuberans. Those with MFH and fibrosarcomas had intermediate survival rates between 60% and 70%, whereas survival was severely impaired in patients with rhabdomyosarcomas, osteosarcomas, and angiosarcomas. The designation of a grade to these tumors would permit a more complete analysis of the prognostic variables of these patients. Although grade would be expected to be the prognostic determinant, other factors such as tumor type (especially angiosarcoma) might exert an independent effect on disease-free or overall survival. The surgical treatment and results are largely related to the site and the cell type. Wide resection with microscopically clear margins offers the best chance for tumor control. This is difficult at most sites because of the limitations on the extent of resection by vital structures. A recent review by Mandard" and co-workers of sarcomas in the extremity, trunk, and head and neck area found that unfavorable prognostic factors included tumor invasion at the margin, extracompartmental status, tumor diameter > 5 cm, and inadequacy of excision. In addition, the
TABLE 2. Head and neck sarcoma series ~
~
Author
Year
Patients
Grade
Resected
(%I
Adjuvant therapy (%)
Survival (%), 5 year mean
Goepfert'
1977
23
91
100
NS
Farr* Greager3 Weber4
1981 1985 1986
242 (50% Pediatric) 53 188
NS NS 69
NS NS 56
32 54 (DFS) NS
Figueiredo' Freedman'
1988 1989
94 (23% Pediatric) 352 (23% Pediatric)
111 8 (35%) II 7 (30%) I 6 (26%) NS 2 (9Yo) NS NS 111 126 (67%) I 12 (68%) N S 50 (27%) NS High 73 (49%) Low 68 (19%) N S 111 (32%) High 104 (59%) Low 72 (41%) NS
NS 82
NS 33
38 67
92
NS
55
83
59
70
'
Farwood7
1990
176
Wanebo et al (present study)
1991
214 (9% Pediatric)
NS, not stated; DFS, disease-free survival
Head and Neck Sarcoma Registry
HEAD & NECK
January/February 1992
5
patients in whom the site and size of the tumor permits wide-field resection with clear margins. Chemotherapy and radiation therapy may augment survival in those in whom clear margins are not achieved." If we exclude the pediatric patients in this series, the registry results are comparable to those reported in some of the large series from major institutions (Table 2). It is interesting t o note how incomplete the table appears; only half of the studies were able to separate out data based upon tumor grade. At the University of Illinois, Division of Surgical Oncology, the most common anatomic site was the neck, and fibrosarcoma was the most common histologic tumor type.3 The overall mean survival time was 59 months, and the disease-free survival at 5 years was 54%. Most of the patients were treated with wide-field resection, with adjuvant radiotherapy or chemotherapy used in selected patients. Of the patients who were long-term survivors, all of their tumors were either well-differentiated or were < 5 cm in diameter. In a large series of head and neck sarcoma patients reported from the Mayo Clinic by Freedman and co-workers6 (consisting of primary soft tissue tumors only), 72% of the tumors were adult and 28% were pediatric patients. The most common sites were paranasal sinus (28%) followed by the neck (25%).Nonorbital rhabdomyosarcoma was the most common tumor type (17%).The overall survival of patients who presented with localized disease was 68% at 5 years and 60% at 10 years. The least successful results were those with angiosarcoma and nonorbital rhabdomyosarcoma. Surgical resection was the
sole method of tumor control in 49%, and adjuvant radiation or chemotherapy was used in 33%. In the present series, RT/CT was given to 127 patients of whom 46 had positive margins. Preliminary analysis showed no beneficial impact of radiation. In fact, patients who were given chemotherapy alone or combined adjuvant therapy had decreased survival. This most likely reflects the advanced nature of the sarcoma treated with this approach and/or the biological behavior of some tumors. Furthermore, we cannot exclude the possibility that patients with poor prognosis received adjuvant therapy while those with good prognosis did not receive radiation or chemotherapy. This is an inherent problem in retrospective studies. The purpose of this registry was to catalog uncommon tumors treated by surgeons with a special interest in head and neck tumors. The registry will also be able to relate this experience to that of large series from individual institutions and to suggest patient groups for which future therapy protocols could be developed. In view of the generally poor outcome of patients with angiosarcoma treated by surgery alone, or even surgery plus radiation in selected patients, a combined modality approach might be suggested for these patients. Other high-grade sarcomas, including rhabdomyosarcoma, osteosarcoma, and MFH > 3 cm, might be better controlled with combined therapy using wide-field resection and chemotherapy and/or radiation. The development of an ongoing protocol perhaps administered through one of the existing cooperative study groups might be one avenue for the members of the Head and Neck Society to pursue.
REFERENCES 1. Goepfert H, Lindberg RD, Sinkovics JG, Ayala AG. Soft-
2. 3. 4.
5.
6. 7.
6
tissue sarcoma of the head and neck after puberty. Arch Otolarygol 1977;103:365-368. Farr HW. Soft part sarcoma of the head and neck. Semin Oncol 1981;8:185- 189. Greager JA, Pate1 MK, Briele HA, Walker MJ, Das Gupta TK. Soft-tissue sarcomas of the adult head and neck. Cancer 1985;56:820-824. Weber RS, Benjamin RS, Peters U,Ro JY, Achon 0, Goepfert H. Soft-tissue sarcomas of the head and neck in adolescents and adults. A m J Surg 1986;152:3:86-92. Figueiredo MTA, Marques LA, Campos-Filho N. Soft-tissue sarcomas of the head and neck in adults and children: experience at a single institution with a review of the literature. Znt J Cancer 1988;41:192-200. Freedman AM, Reiman HM, Woods JE: Soft-tissue sarcomas of the head and neck. A m J Surg 1986;158:367-392. Farwood AI, Hajdu SI, Shiu MH, Strong EW: Soft-tissue
Head and Neck Sarcoma Registry
sarcomas of the head and neck in adults. Am J Surg 1990;160:365-372. 8. Enzinger FM, Wells SW: Soft tissue tumors. St. Louis. CV Mosby, 1988. 9. Torosian MH, Friedrich C, Godbold J , Hajdu SI, Brennan MF. Soft-tissue: initial characteristics and prognostic factors in patients with and without metastatic disease. Semin Surg Oncol 1988;4:13- 19. 10. Mandard AM, Petiot JF, Marnay J , Mandard JC, Chasle J, DeRanieri E, Dupin P, Herlin P, DeRanieri J , Tanguy A, Boulier N, Abbatucci JS. Prognostic factors in soft-tissue sarcomas. Cancer 198963:1437-1451. 11. Mauer HM. Intergroup rhabdomyosarcoma study 11: objectives and study design. J Pediatr Surg 1980;15:371327. 12. Glenn J, Kinsella T, Glatstein E, Tepper J , Baker A, Sugarbarker P, Sindelar W, Roth J, Brennan M, Costa J , Seipp C, Wesley R, Young RC, Rosenberg SA. A random-
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13. 14. 15.
16.
ized prospective trial of adjuvant chemotherapy in adults with soft-tissue sarcomas of the head and neck, breast, and trunk. Cancer 1985;55:1206- 1214. Wanebo HJ, Temple W, Popp M, Douvill CE, Yablonski M. Combination regional therapy for extremity sarcoma: a tri centre study. Arch Surg 1990;125:355-359. Kaplan EL, Meier P. Nonparametric estimation from incomplete observation. J Am Stat Assoc 1958;53:457-481. Pratt CB, Husta OH, Fleming ID, et al. Coordinated treatment of childhood rhabdomyosarcoma with surgery, radiotherapy and combination chemotherapy. Cancer Res 1972;32:606-610. Donaldson SS. The value of adjuvant chemotherapy in
Head and Neck Sarcoma Registry
the management of sarcomas of children. Cancer 1985;55:2184-2197. 17. Johnson DG. Trends in surgery for childhood rhabdomyosarcoma. Cancer 1975;35:916-920. 18. Maurer HM. Intergroup rhabdomyosarcoma study: update, November 1978. Natl Cancer Znst Monogr 1981;56:61-68. 19. Fromm M, Littman P, Raney RB, et al. Late effects after treatment of twenty children with soft-tissue sarcomas of the head and neck. Cancer 1986;57:2070-2076. 20. Rao BN, Santana VM, Fleming ID, et al. Management and prognosis of head and neck sarcomas. Am J Surg 1989;158:373-377.
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7
A Head and Neck Sarcoma Registry was established by the Society of Head and Neck Surgeons to review treatment results of a rare tumor by surgeons with special interest in this anatomic site. Two hundred fourteen patients were analyzed. There were 194 adult tumors and 20 pediatric tumors. The major sites included parotid and neck, 20%; face and forehead, 18%; maxilla and palate, 13%; scalp, 12%; mandible, 11%; paranasal sinuses, 7%; larynx, 2%; and oral cavity, 5%. Eighty-four percent were resectable. The disease-free survival was 56%; overall survival was 70% at 5 years. Major determinants of suwival were adequacy of resection (margins free of tumor) and tumor type. Survival differed according to tumor cell type (tumor grade was not available). Patients with chondrosarcoma and dermatofibrosarcoma had survival approaching 100%. Patients with malignant fibrous histiocytoma (MFH) and fibrosarcoma (FSA) had intermediate survival of 60% to 70%. The worst survival, < 50% at 5 years, occurred in patients with osteosarcoma, angiosarcoma, and rhabdomyosarcoma in decreasing order. This
From the Society of Head and Neck Surgeons, Committee on Research: Department of Surgical Oncology (Drs. Wanebo and Koness), Brown University, Providence, Rhode Island; Department of Surgery (Dr. MacFarlane), St. Paul's Hospital, Vancouver, British Columbia, Canada; University of California at Los Angeles (Dr. Eilber), Los Angeles, California; Houston, Texas (Dr. Byers); Department of Oncology (Dr. Elias), University of Maryland Hospital, Baltimore, Maryland; and Memorial Hospital (Dr. Spiro), New York, New York. Address reprint requests to Dr. Harold J. Wanebo, Roger Williams Medical Center, 825 Chalkstone Avenue, Providence, RI 02908, Accepted for publication July 30, 1991. CCC 0148-6403/92/0101-07$04.00 Q 1992 John Wiley & Sons, Inc.
Head and Neck Sarcoma Registry
suggests a rationale for identifying high-risk patients for prospective adjuvant protocols. This study emphasizes the value of recording uncommon tumors to provide relevant information for future study and possibly therapy. HEAD & NECK 1992:14:1-7
Sarcomas of the head and neck are rare tumors, constituting approximately 15% of all sarcomas, but less than 1%of tumors in this region.lW7Sarcomas are biologically diverse depending on In their type, grade, and site of addition, biologic differences exist in pediatric versus adult sarcomas and in their response to treatment by surgery and adjuvant therapy.11-13 Because of their diversity and their biologic complexity, a Head and Neck Sarcoma Registry was established by the Society of Head and Neck Surgeons to record the number of patients with primary soft-tissue and bone tumors who are being managed by a group of surgeons devoted to the practice of head and neck surgery. The purpose of this registry is to classify these lesions and to correlate the results with other series, as well as to establish an ongoing registry from which new information could be developed, possibly leading to development of clinical trials for specific tumor subtypes. The registry was begun in 1986 with the mailing out of protocols to active mem-
HEAD & NECK
JanuarylFebruary 1992
1
bers of the Society. The results and a retrospective data analysis of the initial 214 patients treated from 1982 to 1990 are reported and discussed. METHODS AND MATERIALS
The records of 214 patients with primary sarcomas of the head and neck that were being managed by individual surgeons or surgical groups from 33 institutions were recorded on a protocol form that was sent to the central office. Each form was reviewed by the project coordinator and entered onto the computer. The original tumor type and grade were recorded by the contributing institution. The basic categories in the protocol included patient initials, age, sex, time of diagnosis, the primary tumor site, the tumor cell type and grade, the initial primary treatment, adjuvant therapy, if any, and follow-up results. The registry asked participating surgeons to provide periodic status reports on patients who were entered. Excluded from analysis were patients with dural or intracranial extradural tumors and those with tumors of nonmesodermal origin or originating from blood-forming organs. Sites included were tumors of the face, neck, parotid and ear, nares and paranasal sinuses, neck, scalp, oral cavity, pharynx, larynx, hypopharynx and ear. The pediatric group included persons < 18 years of age. The analysis was done on a PC computer using an SAS program for statistical analysis. Survival curves were generated by the KaplanMeier method.14 Statistical anaylsis was performed using the log rank or Gehan-Wilcoxon technique and the Cox proportional-hazards model. RESULTS
Data sheets on 214 patients were returned. This included 194 adults and 20 pediatric patient tumors; 38% were female and 62% were male. The median age was 45 years (range, 1-86 years). The age categories included < 18 years, 20 patients; 18-40 years, 74 patients; 41-60 years, 46 patients; and > 60 years, 74 patients. Eightyone percent had soft-tissue tumors and 19%had bone tumors. The presenting symptoms included a mass lesion in 85 patients (49%),pain in 61 patients (35%), and skin change in 25 patients (14%).No presenting symptoms were recorded in 43 patients. The most common tumor types are listed in Table 1. These include angiosarcoma, 31 pa-
2
Head and Neck Sarcoma Registry
TABLE 1. Head and neck sarcoma registry: tumor types.* Grade ~
-~
~
Primary
Recurrent
27 15
2 -
20 14
-
8
2
11 4
-
~~
High-intermediate grade Bone Osteosarcoma Chondrosarcoma Fibrous MFH Fibrosarcoma Smooth muscle Leiomyosarcoma Skeletal muscle Rhabdomyosarcoma Emb rhabdomyosarcoma Vascular Ang iosarcoma Hemangiopericytoma Fatty Liposarcoma Neural Malignant schwannoma Neurofrbrosarcoma Unclassified Other Low-grade tumors Dermatofibrosarcoma protuberans Desmoid tumors Other spindle cell sarcomas Total
3
-
29 6
-
4
-
7
1 2
2 12 10 11 4 5 189
2
-
1 1 -
14
'Cases eliminated from ana/ysis lymphoma 6 , Kaposi's 2, metastatic sarcoma, 2, ameboblastic fibroma, 1
tients; fibrosarcoma, 20 patients; malignant fibrous histiocytoma, 20 patients; osteosarcoma, 29 patients; chondrosarcoma, 15 patients; rhabdomyosarcoma, 11 patients; and embryonal rhabdomyosarcoma, 4 patients. Twelve tumors were unclassified and 2 were stated to be metastatic. Only a small number of tumors were graded (< 20 patients). Eliminated from analysis were lymphoma, 6 patients; Kaposi's, 2 patients; metastatic sarcoma, 2 patients; and ameloblastic fibroma, 1 patient. Sixty patients had tumors involving the neck or parotid area (28%);38 had face and forehead tumors; 28 had involvement of the maxilla and alveolus; 25 had sarcomas of the scalp; and 24 had mandibular involvement. The remaining sites included paranasal sinuses, 16 patients; soft tissue of oral cavity and pharynx, 10 patients; larynx, 5 patients; while in 8 patients the site was not recorded. Tumor size was < 3 cm in 33 patients; 3-5 cm in 64 patients; > 5 cm in 41 patients; and size was not stated in 76 patients. The median tumor size recorded was 4.0 cm.
HEAD & NECK
JanuaryiFebruary 1992
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2
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0
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30
60
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90
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Y a lro MONTHS FROM DX TO DEATH
3n
MONTHS FROM DX TO DEATH
IM
110
FIGURE 1. Kaplan-Meier curves showing the estimated overall survival of 203 patients operated on for primary sarcoma of the head and neck. The mean survival at 5 years was 70%, and at 10 years it was 55%.
FIGURE 3. The overall survival according to size < 3 cm versus > 3 cm or 75 cm showed no significant difference (KaplanMeier plot with Gehan-Wilcoxon determination of significance).
TREATMENT
ease-free survival was 75 months with a 57% disease-free 5-year survival. The relationship of survival according to tumor size is shown in Figure 3. The survival was 84% in patients with tumors < 3 cm compared to 57% and 63% in patients with tumors 3-5 cm or > 5 cm, but these differences were not significant (p = 0.3). The pediatric patients had a 86% survival at 60 months compared to 68% survival in adults (p = 0.1) (Figure 4). The relationship of survival to tumor and type is listed in Figure 5. Bone and soft-tissue survival curves were nearly identical. Patients with dermatofibrosarcoma and chondrosarcoma had excellent survival (approaching loo%), whereas patients with MFH and fibrosarcoma had intermediate survival (60% to 70%). Patients with osteosarcoma, angiosarcoma, and rhabdomyosarcoma had survival < 45% (p < 0.008). Because of the infrequent application of grading, this parameter could not be studied for its survival relationships. Although there was an apparent difference in patients resected for recurrent versus primary sarcomas, this was not
Surgical resection was performed in 179 patients, biopsy only in 24 patients, and ll patients had no surgery. In 163 patients, the resection was done with curative intent (all gross disease removed). The margins were microscopically involved in 27 (17%)of these patients. Wide local excision was performed in 179 patients, and was combined with neck dissection in 15 patients. Other procedures included maxillectomy in 27 patients; mandibulectomy in 20 patients; and orbital exenteration in 5 patients, laryngopharyngectomy in 5 patients. Radiation therapy (RT) was given as an adjuvant to 58 patients; chemotherapy (CT) was given to 31 patients, and combined radiationkhemotherapy (RT/CT) was given to 38 patients. RT and/or CT was given to 46 of 57 patients with involved margins. The overall and disease-free survival curves are shown in Figures 1 and 2. The median survival was 127 months, and the estimated survival at 60 months was 70%. The median dis-
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FIGURE 2. The estimated disease-free survival of 186 patients resected of head and neck sarcoma was 58% and the 10-year disease-free survival was 33% (Kaplan-Meier plot).
Head and Neck Sarcoma Registry
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FIGURE 4. The overall survival of pediatric versus adult patients shows no significant difference.
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January/February 1992
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significant ( p = 0.28) (Figure 6). The results of resection as related to margin involvement shows significantly better survival in patients with clear margins compared with those with involved margins ( p = 0.05) (Figure 7). Patients who received adjuvant therapy (chemotherapy and/or radiation) had lower survival rates than those who received no adjuvant therapy ( p = 0.03). Because of the heterogeneity of therapy administered, the biologic importance of this is unclear. In a multivariant analysis, the only independently significant preditors of improved overall survival were pediatric patients and clear margins ( p = 0.01 and p = 0.005, respectively). DISCUSSION
This review of 214 patients from the Head and Neck Sarcoma Registry is one of the largest series reported of sarcomas from this anatomic site
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FIGURE 6. There was no significant difference in the estimated overall survival between groups with primary versus recurrent sarcoma (Kaplan-Meier curve, Gehan-Wilcoxon statistic).
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and may provide insight into management by surgeons with a committment to head and neck cancers. These tumors are uncommon, considering the rarity of primary sarcomas in the United States (less than 5000 new cases each year) and the infrequency of the head and neck as a primary site for sarcomas (about 15%to 20%). This series epitomizes the biologic and pathologic diversity of sarcomas in this region as reported by other series. Approximately 80% of the tumors originated in soft tissue. The remaining were bone tumors and were approximately evenly divided between osteosarcoma and chondrosarcoma. A relationship of tumor type to site was evident, i.e., angiosarcomas are frequent in the scalp, much less common in other head and neck sites. Fibrosarcoma and malignant fibrohistiocytoma are more common in the parotid and neck and face region, whereas the bone tumors are more common in the maxillafalveolar ridge and mandibular region. Unfortunately, only a small number of these tumors was assigned a grade by the pathologist at the referring institution. Current staging of sarcomas is based on tumor grade; however, it was not applied in most of these cases. Although some of the patients may have predated the time period when grading became established as an essential feature of staging, many of the patients were treated during this time period, but were still not graded by the institutional pathologist for various reasons. This may reflect difficulties in applying grading criteria to these tumors which is a reason for establishing a central sarcoma pathology registry. Only 4 of 7 head and neck sarcoma series collected between 1982 and 1990 were
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primary tumor factors of necrosis, high mitotic count, histiologically undifferentiated tumors, and blood vessel invasion were all related to poor prognosis. Multivariate analysis of the above prognostic factors showed that local recurrence was largely related to the quality of the surgery (ie, wide resection with microscopially clean margins), whereas the occurrence of distant metastases was related to tumor size, margin, presence of tumor necrosis, and the adequacy of excision. This study confirms that the adequacy of the excision is of extreme importance in tumor control, especially if surgery is the primary modality. In this registry, the pediatric patients appeared to do better as a group than the adult patients. Usually these patients present with a more aggressive tumor, largely rhabdomyosarcoma (RMS), and have had severely impaired survival in previous reviews.15-17 About one-third of our pediatric patients had rhabdomyosarcoma. Although the patients with rhabdomyosarcoma did poorly as a group, the pediatric patients did better than the adult patients with this tumor type, possibly because of adjuvant therapy. The Intergroup RMS study has demonstrated an improved prognosis using a multidisciplinary approach,18 although it was subsequently noted that these patients may suffer delayed consequences of combined modality therapy.lg A study of pediatric head and neck tumors by Rao and colleaguesz0 stated that surgery alone may be sufficient initial therapy in the subset of
graded (Table 2). Currently, we are retrieving the slides from individual case contributors for review by a single pathologist experienced in softtissue and bone tumors, to permit a more detailed clinical pathologic review in the future. Survival is directly related to tumor type. Patients with chondrosarcoma have excellent survival, essentially equivalent to that of patients with dermatofibrosarcoma protuberans. Those with MFH and fibrosarcomas had intermediate survival rates between 60% and 70%, whereas survival was severely impaired in patients with rhabdomyosarcomas, osteosarcomas, and angiosarcomas. The designation of a grade to these tumors would permit a more complete analysis of the prognostic variables of these patients. Although grade would be expected to be the prognostic determinant, other factors such as tumor type (especially angiosarcoma) might exert an independent effect on disease-free or overall survival. The surgical treatment and results are largely related to the site and the cell type. Wide resection with microscopically clear margins offers the best chance for tumor control. This is difficult at most sites because of the limitations on the extent of resection by vital structures. A recent review by Mandard" and co-workers of sarcomas in the extremity, trunk, and head and neck area found that unfavorable prognostic factors included tumor invasion at the margin, extracompartmental status, tumor diameter > 5 cm, and inadequacy of excision. In addition, the
TABLE 2. Head and neck sarcoma series ~
~
Author
Year
Patients
Grade
Resected
(%I
Adjuvant therapy (%)
Survival (%), 5 year mean
Goepfert'
1977
23
91
100
NS
Farr* Greager3 Weber4
1981 1985 1986
242 (50% Pediatric) 53 188
NS NS 69
NS NS 56
32 54 (DFS) NS
Figueiredo' Freedman'
1988 1989
94 (23% Pediatric) 352 (23% Pediatric)
111 8 (35%) II 7 (30%) I 6 (26%) NS 2 (9Yo) NS NS 111 126 (67%) I 12 (68%) N S 50 (27%) NS High 73 (49%) Low 68 (19%) N S 111 (32%) High 104 (59%) Low 72 (41%) NS
NS 82
NS 33
38 67
92
NS
55
83
59
70
'
Farwood7
1990
176
Wanebo et al (present study)
1991
214 (9% Pediatric)
NS, not stated; DFS, disease-free survival
Head and Neck Sarcoma Registry
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5
patients in whom the site and size of the tumor permits wide-field resection with clear margins. Chemotherapy and radiation therapy may augment survival in those in whom clear margins are not achieved." If we exclude the pediatric patients in this series, the registry results are comparable to those reported in some of the large series from major institutions (Table 2). It is interesting t o note how incomplete the table appears; only half of the studies were able to separate out data based upon tumor grade. At the University of Illinois, Division of Surgical Oncology, the most common anatomic site was the neck, and fibrosarcoma was the most common histologic tumor type.3 The overall mean survival time was 59 months, and the disease-free survival at 5 years was 54%. Most of the patients were treated with wide-field resection, with adjuvant radiotherapy or chemotherapy used in selected patients. Of the patients who were long-term survivors, all of their tumors were either well-differentiated or were < 5 cm in diameter. In a large series of head and neck sarcoma patients reported from the Mayo Clinic by Freedman and co-workers6 (consisting of primary soft tissue tumors only), 72% of the tumors were adult and 28% were pediatric patients. The most common sites were paranasal sinus (28%) followed by the neck (25%).Nonorbital rhabdomyosarcoma was the most common tumor type (17%).The overall survival of patients who presented with localized disease was 68% at 5 years and 60% at 10 years. The least successful results were those with angiosarcoma and nonorbital rhabdomyosarcoma. Surgical resection was the
sole method of tumor control in 49%, and adjuvant radiation or chemotherapy was used in 33%. In the present series, RT/CT was given to 127 patients of whom 46 had positive margins. Preliminary analysis showed no beneficial impact of radiation. In fact, patients who were given chemotherapy alone or combined adjuvant therapy had decreased survival. This most likely reflects the advanced nature of the sarcoma treated with this approach and/or the biological behavior of some tumors. Furthermore, we cannot exclude the possibility that patients with poor prognosis received adjuvant therapy while those with good prognosis did not receive radiation or chemotherapy. This is an inherent problem in retrospective studies. The purpose of this registry was to catalog uncommon tumors treated by surgeons with a special interest in head and neck tumors. The registry will also be able to relate this experience to that of large series from individual institutions and to suggest patient groups for which future therapy protocols could be developed. In view of the generally poor outcome of patients with angiosarcoma treated by surgery alone, or even surgery plus radiation in selected patients, a combined modality approach might be suggested for these patients. Other high-grade sarcomas, including rhabdomyosarcoma, osteosarcoma, and MFH > 3 cm, might be better controlled with combined therapy using wide-field resection and chemotherapy and/or radiation. The development of an ongoing protocol perhaps administered through one of the existing cooperative study groups might be one avenue for the members of the Head and Neck Society to pursue.
REFERENCES 1. Goepfert H, Lindberg RD, Sinkovics JG, Ayala AG. Soft-
2. 3. 4.
5.
6. 7.
6
tissue sarcoma of the head and neck after puberty. Arch Otolarygol 1977;103:365-368. Farr HW. Soft part sarcoma of the head and neck. Semin Oncol 1981;8:185- 189. Greager JA, Pate1 MK, Briele HA, Walker MJ, Das Gupta TK. Soft-tissue sarcomas of the adult head and neck. Cancer 1985;56:820-824. Weber RS, Benjamin RS, Peters U,Ro JY, Achon 0, Goepfert H. Soft-tissue sarcomas of the head and neck in adolescents and adults. A m J Surg 1986;152:3:86-92. Figueiredo MTA, Marques LA, Campos-Filho N. Soft-tissue sarcomas of the head and neck in adults and children: experience at a single institution with a review of the literature. Znt J Cancer 1988;41:192-200. Freedman AM, Reiman HM, Woods JE: Soft-tissue sarcomas of the head and neck. A m J Surg 1986;158:367-392. Farwood AI, Hajdu SI, Shiu MH, Strong EW: Soft-tissue
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sarcomas of the head and neck in adults. Am J Surg 1990;160:365-372. 8. Enzinger FM, Wells SW: Soft tissue tumors. St. Louis. CV Mosby, 1988. 9. Torosian MH, Friedrich C, Godbold J , Hajdu SI, Brennan MF. Soft-tissue: initial characteristics and prognostic factors in patients with and without metastatic disease. Semin Surg Oncol 1988;4:13- 19. 10. Mandard AM, Petiot JF, Marnay J , Mandard JC, Chasle J, DeRanieri E, Dupin P, Herlin P, DeRanieri J , Tanguy A, Boulier N, Abbatucci JS. Prognostic factors in soft-tissue sarcomas. Cancer 198963:1437-1451. 11. Mauer HM. Intergroup rhabdomyosarcoma study 11: objectives and study design. J Pediatr Surg 1980;15:371327. 12. Glenn J, Kinsella T, Glatstein E, Tepper J , Baker A, Sugarbarker P, Sindelar W, Roth J, Brennan M, Costa J , Seipp C, Wesley R, Young RC, Rosenberg SA. A random-
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13. 14. 15.
16.
ized prospective trial of adjuvant chemotherapy in adults with soft-tissue sarcomas of the head and neck, breast, and trunk. Cancer 1985;55:1206- 1214. Wanebo HJ, Temple W, Popp M, Douvill CE, Yablonski M. Combination regional therapy for extremity sarcoma: a tri centre study. Arch Surg 1990;125:355-359. Kaplan EL, Meier P. Nonparametric estimation from incomplete observation. J Am Stat Assoc 1958;53:457-481. Pratt CB, Husta OH, Fleming ID, et al. Coordinated treatment of childhood rhabdomyosarcoma with surgery, radiotherapy and combination chemotherapy. Cancer Res 1972;32:606-610. Donaldson SS. The value of adjuvant chemotherapy in
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the management of sarcomas of children. Cancer 1985;55:2184-2197. 17. Johnson DG. Trends in surgery for childhood rhabdomyosarcoma. Cancer 1975;35:916-920. 18. Maurer HM. Intergroup rhabdomyosarcoma study: update, November 1978. Natl Cancer Znst Monogr 1981;56:61-68. 19. Fromm M, Littman P, Raney RB, et al. Late effects after treatment of twenty children with soft-tissue sarcomas of the head and neck. Cancer 1986;57:2070-2076. 20. Rao BN, Santana VM, Fleming ID, et al. Management and prognosis of head and neck sarcomas. Am J Surg 1989;158:373-377.
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