An international phase 3 trial in head and neck cancer: quality of life and symptom results: EORTC 24954 on behalf of the EORTC Head and Neck and the EORTC Radiation Oncology Group.

BACKGROUND: The European Organization for Research and Treatment of Cancer (EORTC) 24954 phase 3 randomized clinical trial compared 2 schemes of combined chemotherapy for patients with resectable cancers of the hypopharynx and larynx: sequential induction chemotherapy and radiotherapy versus alternating chemoradiotherapy. The current study reports detailed effects of both treatment arms on health-related quality of life (HRQOL) and symptoms. METHODS: A total of 450 patients aged 35 years to 76 years (World Health Organization performance status (WHO PS) ≤ 2) with untreated, resectable advanced squamous cell carcinoma of the larynx (tumor classification of T3-T4) or hypopharynx (tumor classification of T2-T3-T4) with regional lymph nodes in the neck classified as N0 to N2 with no metastases were randomized in this prospective phase 3 trial into either the sequential arm (control) or the alternating arm (experimental). QOL assessment was performed at randomization; at baseline; at 42 days; and at 6, 12, 24, 36, and 48 months. RESULTS: There were no observed differences with regard to the primary endpoint of Fatigue and secondary endpoint of Dyspnea. Significant differences were found in the secondary endpoints of Swallowing and Speech problems at 42 days after randomization in favor of patients in the sequential arm. Explanatory and sensitivity analysis revealed that the primary analysis favored the sequential arm, but the majority of differences in HRQOL did not exist at the end of treatment, and returned to baseline levels. CONCLUSIONS: In the current study, a trend toward worse scores was noted in the patients treated on the alternating chemoradiotherapy arm but very few differences reached the level of statistical significance. The HRQOL scores of the majority of patients returned to baseline after therapy.

Larynx preservation.

PURPOSE OF REVIEW: Organ preservation, in particular larynx preservation, is a major challenge that has been evaluated during the past 3 decades. This review took in consideration the most recently published articles on this topic. RECENT FINDINGS: There are no new data on this topic but mainly confirming data. Most of the reports underscored that there was still a place for upfront surgery (either partial or total laryngectomy). Nonsurgical approaches are radiotherapy alone or chemotherapy-based protocols with either induction or concomitant chemotherapy added to radiotherapy (with conventional or accelerated fractionation). Different authors underscored that daily practice must follow carefully the selection of patients and monitoring of treatment when applying protocols evaluated in randomized clinical trials. SUMMARY: Larynx preservation is an undisputable advance in larynx cancer management. For early diseases, either surgery (open or endoscopic) or irradiation may control the disease and preserve the larynx function. For advanced cases, chemotherapy-based protocols have been validated, but the best protocol is still to be defined. Importantly some cases still require upfront total laryngectomy. A multidisciplinary approach for decision making is mandatory, whatever the stage.

Induction chemotherapy in head and neck cancer: a new paradigm.

Five hundred and fifty thousand new head and neck cancer cases are diagnosed each year worldwide. They are mostly locally advanced squamous cell carcinoma with a poor prognosis in terms of locoregional and distant failure. A major challenge for patients with locally advanced squamous cell carcinoma is to achieve a high cure rate while preserving functions. Treatment strategies are designed according to the disease stage, primary site, operable status, patient age, and performance status. Surgery, radiation therapy, chemotherapy, and more recently molecular-targeted therapies are part of these strategies, but their sequence remains to be defined. Over the last 30 years, induction chemotherapy has attained an important position in the management of patients with locally advanced squamous cell carcinoma, particularly since the introduction of taxanes. The decision to deliver induction chemotherapy (and its intensification) must be considered in the light of other treatments aiming at better locoregional control (normofractioned radiotherapy, accelerated or hyperfractionated radiotherapy, addition of concurrent chemotherapy, or of targeted therapy) with or without adjuvant treatment. This review summarizes the rationale, these data, and perspectives on induction chemotherapy-based strategies.

Candidates for larynx preservation: the next step?

Nonsurgical treatment approaches to enable larynx preservation in patients who would otherwise undergo laryngectomy have evolved over recent years. Randomized trials have demonstrated that concurrent chemotherapy and radiotherapy is more effective than doublet cisplatin and 5-fluorouracil (5-FU) (PF)-based induction chemotherapy and radiotherapy in enabling larynx preservation. However, concurrent chemotherapy and radiotherapy is also associated with more toxicities than induction PF followed by radiotherapy. The triplet induction regimen of docetaxel, cisplatin, and 5-FU (TPF) is more effective than PF and is now considered to be the standard induction chemotherapy regimen for future larynx preservation trials. Manipulating the postinduction treatment regimen may help to improve larynx preservation rates, and possibly survival, and the use of concurrent chemoradiotherapy and radiotherapy plus the epidermal growth factor receptor inhibitor cetuximab has been investigated in this setting. Determining the most effective treatment approach for larynx preservation will involve conducting a trial comparing concurrent chemotherapy and radiotherapy with sequential TPF induction chemotherapy followed by either radiotherapy or cetuximab plus radiotherapy. Collaboration among international groups is required to assess which approach would be most beneficial in terms of larynx function preservation, disease control, and survival.

Cisplatin, fluorouracil, and docetaxel in unresectable head and neck cancer.

BACKGROUND: Phase 2 studies suggest that the standard regimen of cisplatin and fluorouracil (PF) plus docetaxel (TPF) improves outcomes in squamous-cell carcinoma of the head and neck. We compared TPF with PF as induction chemotherapy in patients with locoregionally advanced, unresectable disease. METHODS: We randomly assigned eligible patients between the ages of 18 and 70 years who had stage III or stage IV disease and no distant metastases to receive either TPF (docetaxel and cisplatin, day 1; fluorouracil by continuous infusion, days 1 to 5) or PF every 3 weeks for four cycles. Patients without progression of disease received radiotherapy within 4 to 7 weeks after completing chemotherapy. The primary end point was progression-free survival. RESULTS: A total of 358 patients underwent randomization, with 177 assigned to the TPF group and 181 to the PF group. At a median follow-up of 32.5 months, the median progression-free survival was 11.0 months in the TPF group and 8.2 months in the PF group (hazard ratio for disease progression or death in the TPF group, 0.72; P=0.007). Treatment with TPF resulted in a reduction in the risk of death of 27% (P=0.02), with a median overall survival of 18.8 months, as compared with 14.5 months in the PF group. There were more grade 3 or 4 events of leukopenia and neutropenia in the TPF group and more grade 3 or 4 events of thrombocytopenia, nausea, vomiting, stomatitis, and hearing loss in the PF group. The rates of death from toxic effects were 2.3% in the TPF group and 5.5% in the PF group. CONCLUSIONS: As compared with the standard regimen of cisplatin and fluorouracil, induction chemotherapy with the addition of docetaxel significantly improved progression-free and overall survival in patients with unresectable squamous-cell carcinoma of the head and neck. (ClinicalTrials.gov number, NCT00003888 [ClinicalTrials.gov].).

Laryngeal Preservation Strategies in Locally Advanced Laryngeal and Hypopharyngeal Cancers.

For long, the treatment of locoregionally advanced laryngeal and hypopharyngeal squamous cell cancers (SCC) consisted of either total laryngectomy (TL) or definitive radiotherapy (RT). The development of induction cisplatin plus 5-fluorouracil (PF) and the correlation between chemosensitivity and radiosensitivity in previously untreated patients opened a new era of treatment aiming at laryngeal preservation (LP). The fundamental concept was to employ induction PF in order to select patients for subsequent treatment with either TL or RT according to tumor response to PF. The first two trials (VALGSG for laryngeal SCC and EORTC 24891 for hypopharyngeal SCC) concluded that such an approach could preserve nearly 60% of larynx without deleterious impact on survival. The EORTC 24954 trial compared 4 cycles of induction PF followed by RT in good responders vs. alternating PF-RT in laryngeal and hypopharyngeal SCC. There was no significant difference in 5-year overall survival with a functional larynx between the two arms (31 vs. 35%). The GORTEC 2000-01 trial compared induction PF to induction PF plus docetaxel (TPF) both followed by RT in good responders in larynx and hypopharynx SCC. The 5-year LP was significantly higher in the TPF arm (60 vs. 39%) but without a difference in survival. The RTOG 91-11 trial compared induction PF followed by RT in good responders vs. concurrent chemoradiotherapy (chemo-RT) vs. RT alone in laryngeal SCC. There was no significant difference in 5-year laryngectomy-free survival between the patients treated with induction chemotherapy (44%) vs. those treated with chemo-RT (47%), both being superior to RT alone (34%). At 5 years, LP was superior with chemo-RT: 84 vs. 71% with induction PF. Two phase II trials explored the role of cetuximab (E) in LP in laryngeal and hypopharyngeal SCC. The TREMPLIN trial compared RT+E or chemo-RT (RT + P) after TPF. The DeLOS-II trial compared TPE followed by RT+E vs. TP followed by RT. However, these trials failed to indicate an advantage for the incorporation of E in the treatment paradigm. To date, two approaches for LP have been validated: induction TPF followed by RT for laryngeal and hypopharyngeal SCC and concurrent chemo-RT for laryngeal SCC. An ongoing trial (SALTORL) is comparing these two approaches, induction TPF and chemo-RT, in laryngeal/ hypopharyngeal SCC.

Prevalence and characteristics of HPV-driven oropharyngeal cancer in France.

BACKGROUND: France has one of the highest incidence of head and neck cancers in Europe. Despite this, the epidemiological impact of high-risk human papilloma virus (HR-HPV) remains poorly investigated. METHODS: We prospective assessed the proportion of oropharyngeal cancers due to HR-HPV in 15 hospitals throughout France. HPV-status was determined by p16-immunohistochemistry, and by detection of HPV-DNA using in situ hybridization. Cancers were classified as HPV-driven if both p16-immunohistochemistry and HPV-DNA assays were positive. Demographical and clinical features were recorded. RESULTS: 291 patients with palatine-tonsil or tongue-base cancers were recruited from March-2011 to July-2012. Of these, 43.1% of samples were p16-positive and 37.7% were positive for both p16 and HPV-DNA. Prognosis was significantly better in patients with HPV-driven cancers, with smoking negatively impacting patients' oncological outcomes. CONCLUSION: In France, more than a third of tonsillar and tongue base cancers are HPV-driven. More research concerning the evolution of HPV-driven cancers over time is needed.

Factors determining length of the postoperative hospital stay after major head and neck cancer surgery.

Hospital stays constitute the main component of costs of cancer treatment. We conducted a prospective study to identify the determinants of the length of stay (LOS) after head and neck cancer surgery (HNCS). Patients who underwent major HNCS with opening of mucosa and with curative intent were enrolled. Data were collected for patient characteristics, type of tumour, surgical procedures and postoperative outcome. LOS defined as the interval between the day of admission for surgery until hospital discharge or death was determined by the Kaplan-Meier method. Independent determinants of LOS were identified using a Cox model. All 260 patients were included. Median LOS was 26 days (range, 3-178). In the multivariate model, four variables remained associated with increased LOS: American Society of Anaesthesiologist's score equal to 3 (hazard ratio 1.62 [1.23-1.99]), duration of surgical procedure >220 min., (HR=1.37 [1.22-1.56]), SSI (HR=2.09 [2.02-2.54]), occurrence of SSI caused by multi-resistant pathogen (HR=2.92 [2.78-3.77]) and occurrence of PP (HR=2.09 [1.78-2.81]). The present results highlighted the long duration of LOS after head and neck cancer surgery. Two variables (duration of surgical procedure and occurrence of nosocomial infections) were associated with LOS and might be improved by appropriate strategies.

Pilot study of neoadjuvant treatment with erlotinib in nonmetastatic head and neck squamous cell carcinoma.

PURPOSE: To determine the safety and efficacy of erlotinib given as neoadjuvant treatment in patients with head and neck squamous cell carcinoma (HNSCC). Further objectives were to identify markers of response to erlotinib and to assess the pharmacodynamic effects of erlotinib in tumor cells. EXPERIMENTAL DESIGN: Patients with locally advanced nonmetastatic HNSCC were treated with erlotinib 150 mg daily pending surgical management. Tumor samples were collected before and after erlotinib treatment and were analyzed using immunohistochemistry. Epidermal growth factor receptor copy number was determined in tumors using CISH analysis. RESULTS: Between November 2003 and December 2005, 35 patients were included in the study. Neoadjuvant treatment with erlotinib in HNSCC patients was well tolerated and did not necessitate modification to routine surgical procedures. Among 31 evaluable patients, erlotinib was given for a median of 20 days. At the time of surgery, tumor shrinkage was observed in nine patients (29%). Immunohistochemistry analyses were done for 31 patients and showed a decrease in phosphorylated tyrosine residues and phosphorylated erk immunostaining after erlotinib treatment. In a retrospective analysis, baseline p21(waf) expression in the basal-like cell layer was statistically positively correlated with clinical response to treatment. Epidermal growth factor receptor copy number did not correlate with response to erlotinib. CONCLUSION: Neoadjuvant treatment of HNSCC with erlotinib was well tolerated. Baseline p21(waf) expression was associated with response to erlotinib and so might be useful as a tool to select patients for erlotinib therapy in this setting.

Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer.

BACKGROUND: We compared concomitant cisplatin and irradiation with radiotherapy alone as adjuvant treatment for stage III or IV head and neck cancer. METHODS: After undergoing surgery with curative intent, 167 patients were randomly assigned to receive radiotherapy alone (66 Gy over a period of 6 1/2 weeks) and 167 to receive the same radiotherapy regimen combined with 100 mg of cisplatin per square meter of body-surface area on days 1, 22, and 43 of the radiotherapy regimen. RESULTS: After a median follow-up of 60 months, the rate of progression-free survival was significantly higher in the combined-therapy group than in the group given radiotherapy alone (P=0.04 by the log-rank test; hazard ratio for disease progression, 0.75; 95 percent confidence interval, 0.56 to 0.99), with 5-year Kaplan-Meier estimates of progression-free survival of 47 percent and 36 percent, respectively. The overall survival rate was also significantly higher in the combined-therapy group than in the radiotherapy group (P=0.02 by the log-rank test; hazard ratio for death, 0.70; 95 percent confidence interval, 0.52 to 0.95), with five-year Kaplan-Meier estimates of overall survival of 53 percent and 40 percent, respectively. The cumulative incidence of local or regional relapses was significantly lower in the combined-therapy group (P=0.007). The estimated five-year cumulative incidence of local or regional relapses (considering death from other causes as a competing risk) was 31 percent after radiotherapy and 18 percent after combined therapy. Severe (grade 3 or higher) adverse effects were more frequent after combined therapy (41 percent) than after radiotherapy (21 percent, P=0.001); the types of severe mucosal adverse effects were similar in the two groups, as was the incidence of late adverse effects. CONCLUSIONS: Postoperative concurrent administration of high-dose cisplatin with radiotherapy is more efficacious than radiotherapy alone in patients with locally advanced head and neck cancer and does not cause an undue number of late complications.

A simple predictive model for postoperative mortality after head and neck cancer surgery with opening of mucosa.

The aim of this study was to determine the risk factors for the mortality during the first 30 days after a major head and neck cancer surgery. Two hundred and sixty one consecutive surgical procedure were prospectively studied at Oscar Lambret Cancer Centre within a 36-months period. Twenty variables were recorded for each patient. The significant risk factors for postoperative mortality were assessed by univariate and multivariate analysis. Overall 30-days mortality rate was 3.83% [95% CI 3.13-4.53]. In univariate analysis identified four risk factors: female gender (odd ratio 4.25 [95% CI 1.03-17.56]), age equal or superior than 70 (odd ratio 5.06 [95% CI 1.35-18.36]), current alcohol addiction (odd ratio 3.65 [1.02-13.06]) and laryngeal location (odd ratio 4.23 [CI 95% 1.18-3.38]). In multivariate analysis only female gender and laryngeal location remained significant. The incidence of postoperative mortality was 1.63% for patients without risk factor and was 6.41% for those with one or two risk factors. This model identifies easily high-risk patients for major head and neck cancer surgery. A multicenter validation is necessary.

Primary mucosal melanoma of head and neck: prognostic value of clear margins.

BACKGROUND: Primary mucosal melanomas of the head and neck (MMHN) are rare and carry a poor outcome. The impact of different treatments on survival is not yet clearly established. METHODS: Twenty patients treated from 1991 to 2004 at a single referral center were retrospectively reviewed. RESULTS: Primary sites were oral mucosa in 14 cases, paranasal sinuses in three cases, and nasal cavities in three cases. The sex ratio was equal to 1, and the median age at diagnosis was 63 years (range, 17-77 y). At presentation, one patient had lymph node metastases, one patient had distant metastases, and one patient had both. Surgery was performed with curative intent in 19 cases (and achieved clear margins in 14 cases). Postoperative radiation therapy was delivered in four cases. The actuarial 2-year and 5-year survival rates were 13/19 and 7/16. The risk factors for death were male gender (RR = 9.3 [1.2-72], P = .024) and positive margins (RR = 21 [1.9-47], P = .013). In addition, we observed three metachromous cancers (one breast cancer, one kidney cancer and one lymphoma) during the follow-up period. CONCLUSION: The present study suggests that obtaining clear margins must be the goal in the treatment of MMNH.

Exclusive low-dose-rate brachytherapy in 279 patients with T2N0 mobile tongue carcinoma.

PURPOSE: To evaluate the therapeutic results obtained with (192)Ir low-dose-rate interstitial brachytherapy in T2N0 mobile tongue carcinoma. PATIENTS AND METHODS: Between December 1979 and January 1998, 279 patients with T2N0 mobile tongue carcinoma were treated by exclusive low-dose-rate brachytherapy, with or without neck dissection. (192)Ir brachytherapy was performed according to the "Paris system" with a median total dose of 60 Gy (median dose rate, 0.5 Gy/h). RESULTS: Overall survival was 74.3% and 46.6% at 2 and 5 years. Local control was 79.1% at 2 years and regional control, respectively, 75.9% and 69.5% at 2 and 5 years (Kaplan-Meier method). Systematic dissection revealed 44.6% occult node metastases, and histologic lymph node involvement was identified as the main significant factor for survival. Complication rate was 16.5% (Grade 3, 2.9%). Half of the patients presented previous and/or successive malignant tumor (ear-nose-throat, esophagus, or bronchus). CONCLUSION: Exclusive low-dose-rate brachytherapy is an effective treatment for T2 tongue carcinoma. Regional control and survival are excellent in patients undergoing systematic neck dissection, which is mandatory in our experience because of a high rate of occult lymph node metastases.

Multivariate analysis of risk factors for wound infection in head and neck squamous cell carcinoma surgery with opening of mucosa. Study of 260 surgical procedures.

The goal of this prospective study was to determine risk factors for wound infections (WI) for patients with head and neck cancer who had undergone surgical procedures with opening of upper aerodigestive tract mucosa in multimodal therapeutic approaches. Two hundred and sixty consecutive surgical procedures were studied at Oscar Lambret Cancer Center over a 36-month period. Twenty-five variables were recorded for each patient. Statistical evaluation used chi2 test analysis (categorical data) and Mann-Whitney test (continuous variables). Multivariate analysis was performed with logistic regression model. The overall rate of WI was 45% (117/260). Univariate analysis indicated that five variables were significantly related to the likelihood of WI: male sex (p = 0.03), previous chemotherapy (p = 0.009), duration of previous hospital stay (p = 0.013), hypopharyngeal location (p = 0.003), post-laryngectomy tracheostoma (p < 0.001). Multivariate analysis identified only one major risk factor for WI: post-laryngectomy tracheostoma (Odd Ratio 1.9 [95% CI 1.3-3]; 33% versus 64%; p = 0.001). Despite antibiotic prophylaxis, WI occurrence is high. This study identified one major risk factor, post-laryngectomy tracheostomy. Long-term curative antibiotherapy must be evaluated in cancer head and neck surgery requiring post-laryngectomy tracheostoma.

Prognosis of hypercalcemia in aerodigestive tract cancers: study of 136 recent cases.

Recent data issuing the prognostic impact of hypercalcemia on outcome of aerodigestive tract cancers are spare. To assess the prognosis and the survival of head and neck cancer patients with hypercalcemia, we reviewed 136 recent successive cases, including also oesophageal and lung cancers. Data were collected from a retrospective database (July 2002-January 2004). Hypercalcemia was defined by calcemia level above 2.55 mmol/l. Univariate analysis for prognosis was performed with Mann-Whitney test (continuous variables) and Odd Ratio with 95% confidence interval (categorical variables). The primary locations were : oropharynx and oral cavity (79, 58%), hypopharynx (13, 9.5%), larynx (10, 7.3%), oesophagus (17, 12.5%) and lung (17, 12.5%). There were 23 females and 123 males, with a median age of 53 (18-86). The incidence of bone metastasis was low: 20/136, 14.5%. At cancer diagnosis, 32 hypercalcemia were observed. With a median follow-up of 88 days (2-553), we observed 98 deaths (overall mortality=72%). The median overall survival was 35 days (2-553+). The pejorative prognostic factors were: male gender (OR=2.64 CI 95% 1.07-6.82), age inferior to 50 (OR=2.67 CI 95% 1.23-5.8), presence of distant metastasis (OR=4.45 CI 95% 1.8-11.01), elevation of alkaline phosphatases (OR=7 CI 95% 2.73-17.9) and need of hospitalization for intravenous hydratation (OR=5.11 CI 95% 1.99-13.17). We observed 39 recurrences of hypercalcemia. The predictive factors for recurrence of hypercalcemia were: age superior to 50 (OR=4.61 CI 95% 2.02-10.52), male gender (OR=38.22 CI 95% 12.2-89), calcemia level superior to 2.7 mmol/l (OR=3.08 CI 95% 1.42-6.64) and absence of diphosphonates (bisphosphonates: OR=2.16 CI 95% 1.01-4.63). Despite use of diphosphonates (infusions of pamidronate), hypercalcemia is associated with very poor prognosis. Tumour location and level of calcemia had no prognostic value.

Cancer of the larynx.

In Europe, laryngeal cancer accounts for only 2-5% of all cancers, the incidence being much higher among males than among females. Smoke and alcohol represent the major behavioural risk factors. Several carcinogens, occupations and vitamin deficiencies have been associated with laryngeal cancer. A genetic susceptibility to environmental risk factors and carcinogens is recognized. Hoarseness is the main symptom for which patients call for medical consultation. Mucosa is the most common histologic site of the primary lesions considered in the present chapter. Nodal involvement, the site and volume of the primary tumour, and some genes expression represent the major prognostic factors. A high death rate for not cancer-related events is to be pointed out. The loco-regional extent of the disease determines the success of cure. Surgery and radiotherapy represent the main therapeutic options. The choice between these two procedures is often controversial.

Cancer of the oropharynx.

Oropharyngeal cancer is a rare tumour. Tobacco use and alcohol consumption are recognised as major risk factors. Several carcinogens, occupational exposures and vitamin deficiencies represent the most significant predisposing factors. A varying host susceptibility to carcinogens can be inferred. Carcinoma of the oropharynx has to be suspected whenever sore throat, odynophagia, and ear-ache are described by the patient. Biopsy is mandatory for the definitive diagnosis. TNM classification is crucial for treatment decision-making, while stage grouping is less important. Prognostic factors are treatment-related. Standard treatment of T1-T2 tumours is radiation therapy, for T3 and T4 tumour treatment options are controversial. More advanced tumours can be treated either with surgery followed by conventional radiotherapy or by combined chemo-radiation. Non-conventional fractionation radiotherapy in combination with chemotherapy may represent a third option. Acute toxicity needs to be managed promptly. Late sequelae are less known. Treatment of such tumours requires a multidisciplinary approach within experienced centres.

A comparative study of the efficacy and safety of fluconazole oral suspension and amphotericin B oral suspension in cancer patients with mucositis.

This randomized study compared the efficacy and safety of fluconazole suspension with that of amphotericin B suspension in patients with head and neck cancer who were suffering from candidiasis during cancer treatment with radiotherapy and/or chemotherapy. A total of 123 evaluable patients received 50 mg fluconazole once daily and 120 evaluable patients received 0.5 g amphotericin B thrice daily for 7-14 days depending on clinical response. A positive culture result was obtained in 121 of 264 (46%) patients; Candida albicans was most common. At the end of treatment, fluconazole and amphotericin B were equivalent (CI(90) of -10.7 to +14.9) in terms of clinical cure and improvement, but the rate of mycologic cure was higher for fluconazole (48%) than amphotericin B (35%). The incidence of adverse events was 39% for fluconazole and 44% for amphotericin B. Fluconazole suspension appeared effective and safe.

Head and neck soft tissue sarcomas of adult: prognostic value of surgery in multimodal therapeutic approach.

Adult head and neck soft tissue sarcomas (AHNSTS) are rare, and data concerning treatment results are spare. To assess clinico-pathological characteristics, management prognostic factors, and survival of AHNSTS, we reviewed our experience of 28 recent successive new cases. Data were collected from a retrospective database (1997-2002). Aggressive fibromatosis, dermatofibrosarcoma, Kaposi sarcoma, chondrosarcoma and osteogenic sarcoma were excluded. Univariate analysis for prognostic factors was performed with chi2 test with Yates correction. The median age was 45.7 years (range: 18-86). The male/female ratio was 15/13. The most common subtypes was rhabdomyosarcoma (seven cases). Twenty-two patients presented with previous inadequate resection performed elsewhere before admission. The most common location was neck muscles (11 cases). Nineteen patients had surgery (complete resection in 13 cases). Associated treatments were neoadjuvant chemotherapy, adjuvant chemotherapy and postoperative radiotherapy in respectively, 4, 3 and 10 cases. The 2-year overall survival was 56%. Rhabdomyosarcomas (p = 0.005) and inadequate resection (p = 0.04) were associated with poor outcome. Large resection of AHNSTS in a multimodality approach may afford the best chance of disease control.