Laryngeal preservation with induction chemotherapy for hypopharyngeal squamous cell carcinoma: 10-year results of EORTC trial 24891.

BACKGROUND: We report the 10-year results of the EORTC trial 24891 comparing a larynx-preservation approach to immediate surgery in hypopharynx and lateral epilarynx squamous cell carcinoma. MATERIAL AND METHODS: Two hundred and two patients were randomized to either the surgical approach (total laryngectomy with partial pharyngectomy and neck dissection, followed by irradiation) or to the chemotherapy arm up to three cycles of induction chemotherapy (cisplatin 100 mg/m(2) day 1 + 5-FU 1000 mg/m(2) day 1-5) followed for complete responders by irradiation and otherwise by conventional treatment. The end points were overall survival [OS, noninferiority: hazard ratio (preservation/surgery) ≤ 1.428, one-sided α = 0.05], progression-free survival (PFS) and survival with a functional larynx (SFL). RESULTS: At a median follow-up of 10.5 years on 194 eligible patients, disease evolution was seen in 54 and 49 patients in the surgery and chemotherapy arm, respectively, and 81 and 83 patients had died. The 10-year OS rate was 13.8% in the surgery arm and 13.1% in the chemotherapy arm. The 10-year PFS rates were 8.5% and 10.8%, respectively. In the chemotherapy arm, the 10-year SFL rate was 8.7%. CONCLUSION: This strategy did not compromise disease control or survival (that remained poor) and allowed more than half of the survivors to retain their larynx.

Hyperselective intra-arterial preoperative chemotherapy in patients with squamous cell carcinoma of the oral cavity: preliminary results.

OBJECTIVES: To investigate radiological response and findings after Intra Arterial Chemotherapy (IAC) for patients with Squamous Cell Carcinoma (SCC) of the oral cavity. MATERIALS AND METHODS: Patients received 1-2 cycles of IAC. Radiological assessment was performed on day 7 and day 21 after each cycle using CT scan and MRI. RESULTS: Six patients (median age: 52, ranging 46-60; male/female: 5/1) received 10 cycles (4 patients received 2 cycles). Primary tumors were floor of the mouth (4 patients) and oral tongue (2 patients). TNM classification was T2N0-2b in 3 patients and T4N0-1 in 3 patients. All patients had good locoregional/systemic tolerance and 3 showed clinical objective response (OR). Four patients were evaluable on both CT and MRI, 1 patient on MRI only and 1 patient did not tolerate imaging. Three patients showed OR both on CT and MRI, 1 patient showed stable disease (SD) on CT and OR on MRI and 1 patient showed SD on MRI. Contrast-enhancement of hemiperfused tongue was reported in all evaluable patients. Two patients presented intratumoral necrosis and 5 patients displayed local edema (MRI). One patient had modification of the sternocleidomastoid muscle after IAC. CONCLUSION: Radiological modifications were observed in the infused area and correlated well with clinical response. This study is ongoing.

[Building Clinical Target Volume in laryngeal cancers using knowledge about modes of invasion of each location]. / Etablissement des volumes cibles anatomocliniques (Clinical Target Volume) pour les cancers laryngés en fonction de la localisation de départ et des modalités d'extension.

The purpose of this article is to propose a building model to delineate Clinical Target Volume in laryngeal cancers (squamous cell carcinoma). This model uses histological knowledge about the spread of laryngeal cancers. Firstly is described the spread, depending on primary location and anatomic structures. Then illustrated examples on Computed Tomography are provided. This delineation approach appears to be useful with 3D-CRT and IMRT for adapting dose delivery to the complex spread of laryngeal cancer.

Cytology vs molecular analysis for the detection of head and neck squamous cell carcinoma in oesopharyngeal brush samples: a prospective study in 56 patients.

Oesopharyngeal brush (OPB) sampling with cytological analysis can yield exfoliated cells from asymptomatic tumours of the upper aero-digestive tract and the oesophagus. In this study, we compared cytological evaluation and molecular analysis for the detection of exfoliated cancer cells sampled with an OPB. A total of 56 patients with a known unique head and neck squamous cell carcinoma (HNSCC) and five healthy controls were enrolled prospectively. Exfoliated cells from these 61 patients were collected with an OPB before initial endoscopy. p53 mutations and UT 5085 microsatellite instability (MI) were analysed in the HNSCC tumour, lymphocytes and the corresponding OPB DNA samples. p53 mutations and UT5085 MI were detected in 31 out of 56 and 14 out of 56 HNSCC, respectively, but not in any of the five controls. Direct sequencing of p53 was able to detect mutations in OPB DNA in only two out of 29 patients harbouring a p53-mutated primary tumour. Microsatellite instability was detected in OPB DNA of 11 out of 13 informative (bandshift detected in tumour) patients, whereas cytological analysis detected abnormal cells in only six of the same 13 patients (P=0.03). In informative patients, all positive OPB samples at cytological analysis were also positive at molecular analysis of UT5085, and both analyses confirmed the two negative samples. Molecular analysis of OPB from eight uninformative patients and from five healthy controls were all negative. OPB sampling with MI-based molecular analysis could be efficient for early detection of recurrent HNSCC. This result prompts us to use other microsatellite markers in order to maximise the percentage of informative patients.

[Swallowing study with kinetic MRI using a single shot fast spin echo sequence in healthy volunteers and patients treated for head and neck cancer]. / Etude de la déglutition par ciné-IRM utilisant la séquence single shot fast spin écho (SSFSE) chez des volontaires sains et des patients traités pour un cancer ORL.

PURPOSE: To evaluate the single shot fast spin echo sequence (SSFSE) rapid MRI sequence for swallowing study, to describe the swallowing phases analyzable by kinetic MR Imaging and to show the advantages and the limits of the method in patients treated for head and neck cancer. METHODS AND MATERIALS: A preliminary study was conducted in 8 healthy volunteers and 11 patients treated for a head and neck cancer between June 1999 and April 2001. Examinations were obtained on a 1.5 T machine using a multi-slice SSFSE sequence with an acquisition time of 1 second/slice. The different phases of swallowing were analyzed. Examinations were done with and without water ingestion. RESULTS: Kinetic MRI allows to clearly analyze the anatomy and the dynamic of the tongue, the soft palate, the hyoid bone, the larynx and the posterior pharyngeal wall. The hypopharyngeal and esophageal phases were suboptimally assessed. CONCLUSION: Kinetic MRI allows to clearly analyze the oral and early pharyngeal phases of swallowing, which can be correlated with normal and surgically reconstructed areas in spite of the low temporal resolution and the non-physiologic position. It is simple and rapid to perform and may be useful in treated patients with head and neck cancer.

[Pediatric rhabdomyosarcoma of the infratemporal fossa]. / Les rhabdomyosarcomes de la fosse infratemporale de l'enfant.

OBJECTIVE: Prognosis of rhabdomyosarcoma of the infratemporal fossa is generally poor. We report our experience. MATERIAL AND METHODS: Twenty-three children with rhabdomyosarcoma of the infratemporal fossa were treated at the Gustave Roussy and Curie Institutes between 1984 and 1999. Seventeen children received radiotherapy (group 1), four children were treated surgically with or without postoperative radiotherapy (group 2), and two children received no further treatment after chemotherapy (group 3). RESULTS: In group 1, there were 10 local recurrences and one metastatic failure; all 11 children died from their disease. Nodal recurrence was salvaged successfully in one other with chemotherapy and surgery. In group 2, three children were disease free at 3 years and one died of local recurrence. In group 3, one child experienced a local recurrence successfully salvaged with radiotherapy. This child was disease free at 3 years. The other child developed local recurrence and died. DISCUSSION: Overall survival rate in our patients was 50%. Local control remained the main prognostic factor for survival. Surgery has already been shown to improve local control in other localizations of rhabdomyosarcoma. If residual tumor tissue remains after neo-adjuvant chemotherapy, surgery should be considered in a multidisciplinary discussion of therapeutic options. Indications for postoperative radiotherapy depend on age and histological features of the surgical specimen.

[Laryngeal Preservation with Induction Chemotherapy. Experience of two GETTEC Centers, Between 1985 and 1995]. / Préservation laryngée par chimiothérapie d'induction.

This is a retrospective study of laryngeal preservation in endolaryngeal cancer with induction chemotherapy and radiotherapy for good responders. Between 1985 and 1995, 104 patients were treated in Institut Gustave Roussy (87 patients) and in Limoges (17 patients). The overall survival for the whole population was 76% and 69% at 3 and 5 years respectively, with a 36% rate of laryngeal preservation. In this retrospective series of patients, the single prognostic factor affecting survival was arytenoid mobility before treatment (66% and 55% at 3 years vs 85% and 82% at 5 years; p<0.004). Loco-regional failures were higher (33% vs 15%, p<0.03), and laryngeal preservation was lower (18% vs 51%) among patients with a fixed arytenoid (49 pts), compared with patients with a non fixed arytenoid (55 pts) ). The percentages of patients with a fixed arytenoid could explain the conflicting results of the two randomized studies of laryngeal preservation in laryngeal cancer.

Subtotal laryngectomy with cricohyoidopexy as first treatment procedure for supraglottic carcinoma: Institut Gustave-Roussy experience (146 cases, 1974-1997).

PATIENTS AND METHODS: Between 1974 and 1997, 297 patients underwent a subtotal laryngectomy at the Institut Gustave-Roussy; 146 of these patients underwent cricohyoidopexy (CHP) for a supraglottic primary as their first treatment. The majority of patients were men (137) aged from 33 to 78 years (median 54 years). The tumour stage at presentation was T1 in 2, T2 in 87, T3 in 53 (preepiglottic space involvement), and T4 (minimal thyroid cartilage invasion) in 4 patients. One hundred and twenty-five patients were N0 (86%) and 21 patients were Np (palpable); 98% had homolateral and 55% had bilateral neck dissections. RESULTS: One patient died postoperatively of a myocardial infarction and 68% patients had an uneventful course. Aspiration was the commonest complication (23 patients, 19%). The median time to removal of the tracheotomy cannula was 10 days and for the nasogastric tube 21 days during the past 10 years. Completion of subtotal laryngectomy into total laryngectomy was done in 21 cases (15%): eight times because of oncological events [five local failures, two second primary (hypopharynx), one positive margin] and 13 times because of aspiration (9%). There were six local failures (4%) and eight nodal failures (5%). The rates of distant metastases and second primaries were 6% and 16% respectively. Half of the local and nodal failures were subsequently sterilized. Findings at death were two local recurrences, four nodal recurrences, eight distant metastases, and 11 second primaries. The 3- and 5-year overall survival rates were 92% and 88% respectively, with an overall laryngeal preservation rate of 86%. CONCLUSION: When supraglottic laryngectomy is not feasible for supraglottic cancer, subtotal laryngectomy with CHP is a safe and effective oncological procedure, with preservation of satisfactory laryngeal function.

Full dose reirradiation combined with chemotherapy after salvage surgery in head and neck carcinoma.

BACKGROUND: The purpose of this study was to analyze the tolerance and efficacy of full dose reirradiation combined with chemotherapy in patients with head and neck carcinoma (HNC) with a high risk of recurrence after salvage surgery. METHODS: Between 1991 and 1996, 25 patients having a recurrence or a second primary tumor in a previously irradiated area (> 45 grays [Gy]) were entered in this prospective study. All of them received salvage surgery and had a positive surgical margin and/or lymph node involvement with capsular rupture (N+R+). Adjuvant radiochemotherapy was given, delivering 60 Gy per 30 fractions with concomitant hydroxyurea and 5-fluorouracil. The median total cumulative dose of the 2 irradiations was 118 Gy. The median follow-up after the second irradiation was 66 months. RESULTS: During the reirradiation course, Grade 3 and 4 mucositis were observed in 40% and 12%, respectively. Analysis of late effects (> 6 months after reirradiation) showed that 16% of the patients had osteoradionecrosis and 40% had Grade 2-3 cervical fibrosis (Radiation Therapy Oncology Group scoring system). The patterns of failure were as follows: local only (n = 9), lymph node only (n = 2), local and lymph node only (n = 1), and metastatic (n = 4). The 4-year survival rate after reirradiation was 43% (95% confidence interval, 25-62). CONCLUSIONS: Full dose reirradiation combined with chemotherapy after salvage surgery in high risk patients with HNC was feasible with an "acceptable" toxicity and led to a relatively good 5-year survival rate. These results prompted the authors to initiate a multicentric randomized trial that is ongoing (GETTEC-GORTEC 99-01) to evaluate the benefit of adjuvant radiochemotherapy in these types of patients.

Surgical management of posterior pharyngeal wall carcinomas: functional and oncologic results.

BACKGROUND: The optimal primary treatment for posterior pharyngeal wall tumors remains controversial. METHODS: To assess the relevance of surgical treatment from a functional and oncologic point of view, we reviewed the cases of 77 patients surgically treated between 1984 and 1995. Among them 23 had been previously irradiated. Fifty-five patients underwent a conservative surgery (CS) sparing the larynx; 19 direct closures, 6 reconstructions of the posterior wall with a thoracic myocutaneous flap, 15 with a platysma flap, and 15 with a free forearm flap were performed. Twenty-two patients underwent radical surgery (RS). All previously untreated patients had postoperative radiotherapy. The functional assessment concerned the CS group. Oncologic results, especially local control and survival were studied for the whole group. RESULTS: Of the 55 patients who underwent CS, 53 (96%) had their canula and 49 (89%) their feeding tube removed. At 1 year, in the platysma and free forearm groups, 21 of the 24 assessable patients were back to exclusive oral intake. For patients treated by primary surgery followed by radiotherapy, the rate of local failure was 11% (18% for tumors greater than 4 cm), and the 5-year survival rate was 35%. For patients who had previous radiotherapy, the rates were, respectively, 52% and 16%. CONCLUSION: The satisfactory functional results, caused by the improvement of reconstructive procedures, allow conservative surgery even in the case of large tumors. Oncologic results, especially local control, suggest that primary surgery followed by radiotherapy is effective for the treatment of posterior wall cancer. The oncologic results of surgery in a previously irradiated area are poor, and CS is not recommended in these cases.

[Mandibulotomy for cancer of the oral cavity and oropharynx: functional and carcinologic outcome in 107 cases]. / La chirurgie par voie de mandibulotomie dans les cancers de la cavité buccale et de l'oropharynx. Résultats fonctionnels et carcinologiques sur une série de 107 cas.

We report a series of 107 patients who underwent mandibulotomy at the Gustave-Roussy Institute, France for cancer of the oral cavity and orophaynx between 1998 and 1996. The most common tumor site was the base of the tongue. Most cases were stage T2 or T3. Postoperative radiotherapy was employed except in those who had previous irradiation, either for the same tumor (12 cases) or another cancer (16 cases). The different types of mandibulotomies and osteosynthesis methods were analyzed in relation to postoperative course and functional and oncological outcome at mean follow-up of 6 years. Osteitis was the most frequent complication (14%) requiring hemimandibulectomy in 5 cases. Complications occurred particularly when osteosynthesis was in the pre-or postoperative irradiation field. Osteosynthesis was definitive in 79.4% with good functional results in 76.5%. Previous radiotherapy or use of flaps for closure gave poor function results. We emphasize the advantages of anterolateral mandibulotomy and titanium plates. The local control rate was 81.5% at 6 months and overall survival rat was 51.5% at 5 years with no significant impact of tumor site on survival.

U-shaped free jejunal transplantation: improved technique and indications.

Reconstruction of the oropharynx and the hypopharynx is difficult due to their wide diameters. We report eight cases of circumferential pharyngolaryngectomies for epidermoid carcinomas of the hypopharynx extended to the oropharynx and classified T4. Reconstruction was performed with a U-shaped free jejunal transplantation. This specific technique consists of a side to side anastomosis between two loops of jejunum. It facilitates reconstruction at the level of the oropharynx and diminishes postoperative complications.

A randomized study of very accelerated radiotherapy with and without amifostine in head and neck squamous cell carcinoma.

PURPOSE: The aim of this study was to assess whether amifostine could minimize acute mucositis induced by a very accelerated irradiation regimen in patients with advanced head and neck squamous cell carcinoma (HNSCC). METHODS AND MATERIALS: Between May 1996 and February 1998, 26 patients with an inoperable nonmetastatic Stage IV HNSCC were entered in this study. The treatment consisted of very accelerated radiotherapy given 64 Gy in 3.5 weeks. The patients were randomized to receive or not 150 mg/m(2), amifostine (Ethyol, U.S. Bioscience) 15-30 min prior to each radiation session. RESULTS: Of the 13 patients who received amifostine, definitive interruption of amifostine occurred in 5 cases (38%), due to tolerance problems (vomiting, liver enzyme elevation, generalized erythema). The distribution of Grade 4 mucositis (WHO) was 1 case versus 8 cases, with and without amifostine, respectively. The mean duration of "at least Grade 3" mucositis (WHO) was 25.1 days versus 49.2 days with and without amifostine (p = 0.03). In the amifostine group, 11/13 of the patients required a feeding tube (nasogastric tube or medical gastrostomy), because of acute mucositis, whereas in the control group a feeding tube was necessary in all cases. The mean duration of the use of this feeding tube was 1 month versus 2.5 months with and without amifostine respectively (p < 0.01). Local-regional control was not different between both arms with a median follow-up of 15 months. CONCLUSION: Despite the limited number of patients, this pilot randomized study suggests that amifostine was able to markedly reduce the severity and duration of mucositis induced by very accelerated radiotherapy. However, the tolerance of this twice daily amifostine schedule was relatively poor.

Randomized trial of neoadjuvant chemotherapy in oropharyngeal carcinoma. French Groupe d'Etude des Tumeurs de la Tête et du Cou (GETTEC).

The objective of the study was to evaluate the effect of neoadjuvant chemotherapy on the survival of patients with oropharyngeal cancer. Patients with a squamous cell carcinoma of the oropharynx for whom curative radiotherapy or surgery was considered feasible were entered in a multicentric randomized trial comparing neoadjuvant chemotherapy followed by loco-regional treatment to the same loco-regional treatment without chemotherapy. The loco-regional treatment consisted either of surgery plus plus radiotherapy or of radiotherapy alone. Three cycles of chemotherapy consisting of Cisplatin (100 mg/m2) on day 1 followed by a 24-hour i.v. infusion of fluorouracil (1000 mg/m2/day) for 5 days were delivered every 21 days. 2-3 weeks after the end of chemotherapy, local treatment was performed. The trial was conducted by the Groupe d'Etude des Tumeurs de la Tête Et du Cou (GETTEC). A total of 318 patients were enrolled in the study between 1986 and 1992. Overall survival was significantly better (P = 0.03) in the neoadjuvant chemotherapy group than in the control group, with a median survival of 5.1 years versus 3.3 years in the no chemotherapy group. The effect of neoadjuvant chemotherapy on event-free survival was smaller and of borderline significance (P = 0.11). Stratification of the results on the type of local treatment, surgery plus radiotherapy or radiotherapy alone, did not reveal any heterogeneity in the effect of chemotherapy.

[Midface reconstruction with free flaps]. / Reconstruction de l'étage moyen de la face par transplants libres.

STUDY AIM: Midface is situated between the occlusal plane and the transverse midorbital plane. The aim of midface reconstruction is to restore the bony and soft tissue contour of the face, to obtain a rigid support for the velum, to allow oronasal separation, and to allow support for the orbit and obliteration of the maxillary sinus in order to restore the main functions: respiration, speech, deglutition, mastication, olfaction, vision. PATIENTS AND METHODS: Between 1988 and 1997, 65 patients with defects to the midface in relation with cancer (n = 60), gunshot (n = 3), or congenital malformation (n = 2), underwent reconstruction with one or more transplants: forearm (n = 21), latissimus dorsi (n = 23), scapula (n = 12), composed subscapula (n = 10), and fibula (n = 4). Forty-seven of the patients were men and 18 were women. The mean age was 56 years (12-90 years). In patients with cancer, tumoral resection was immediately followed by midface reconstruction in the last 43 cases. Free flaps were selected for reconstruction of each part of the midface: cheek, nose, orbit floor, maxillary and palate. RESULTS: One post-operative death occurred (1.5%). The morbidity rate (18.7%) included necrosis of the free flaps in four cases. Average resumption of oral intake was ten days. The mean time to discharge was 17 days. Aesthetic and functional results were rated good or excellent in 53 patients. After one year, 52 patients were alive. Oral intake was normal in 48 patients, and mixed in four. Speech was excellent or good in 49 patients. From amongst the patients, 80% were able to find a job. CONCLUSION: Free flaps with micro surgery provides an optimal, functional, morphological and aesthetic outcome. Patients with advanced cancer of the midface are best managed through a multidisciplinary team approach. Microsurgical reconstruction represents the technical state of the art in case of extensive and complex midface defect.

[Primary synovial sarcoma of head and neck. Materials of The Gustave Roussy Institute. Report of 13 cases]. / Synovialosarcomes cervico-faciaux. Expérience de 1'Institut Gustave Roussy. A propos de 13 cas.

This report presents the result of our experience with 13 primary synovial sarcoma of the head and neck. The 9 males and 4 females had a median age of 32 years. The predominant location of the tumor was the pharynx, treatment consist of surgical excision alone or associated with post-operative radiotherapy or chemotherapy. Mean follow-up was 48 month. Local recurrence occurred in 2 patient, 4 patient died of pulmonary metastasis. The five year survival rate was 55%. Favorable prognostic findings included age < 20 years and complete initial resection.

[Organ preservation in ORL oncology: myth or reality. The case for laryngeal preservation]. / La conservation d'organes en cancérologie ORL: mythe ou réalité. A propos de la conservation laryngée.

The conservation of a functional larynx is an important goal in the various attempts to improve the treatment of locally-advanced pharyngo-laryngeal cancers. Several axes have been followed: conservative surgery (subtotal laryngectomy), exclusive irradiation (with conventional or non-conventional fractionation), initial chemotherapy (followed by surgery or irradiation) or concomitant chemotherapy-radiotherapy. The numerous studies, including some major randomised trials, dealing with the issue of larynx preservation are reviewed in the present article. A critical comparison of their results and its integration in a consistent approach are difficult, especially because the different options are aimed at different patients. Total laryngectomy and its psychological and social consequences can be avoided in a significant number of patients, although the long term functional outcome is poorly known and the choice of the optimal treatment modality is largely dependent on the expertise and experience of the medical team.

Variations in tumour oxygen tension (pO2) during accelerated radiotherapy of head and neck carcinoma.

The study was performed to assess the effect of accelerated radiotherapy on oxygenation of primary tumours and metastatic nodes in patients with advanced head and neck tumours. In 14 patients with head and neck tumour, oxygen tension (pO2) was evaluated in normal tissues and tumours (primary tumour or metastatic neck node) before (0 Gy) and after 2 weeks (32 Gy) of accelerated radiotherapy (70 Gy in 3.5 weeks, with three daily fractions). Radiotherapy was combined with carbogen breathing in 5 patients. pO2 was measured using a polarographic technique. For pooled normal tissues, median pO2 was 38 mmHg before treatment and 46 mmHg after 2 weeks. For tumours, very low values (< 2 mmHg) represented 20% of the recorded values before treatment and 10% after 2 weeks. The relative increase in tumour oxygenation was more pronounced for primary tumours (median pO2 12 mmHg before treatment versus 26 mmHg after 2 weeks, P < 0.05) than for metastatic nodes (respectively, 20 and 27 mmHg P = 0.1). For the 5 patients who breathed carbogen during accelerated radiotherapy, the median pO2 was 44 mmHg at 2 weeks, compared with 13.5 mmHg before treatment (P = 0.05). Very low pO2 values, corresponding to tumour hypoxia, were found in the tumours (primary and metastatic neck nodes) prior to accelerated treatment. During the first 2 weeks of accelerated treatment, an increase in median pO2 was found in nine of the 14 tumours, together with a decrease in the frequency of very low values.

Full-dose reirradiation for unresectable head and neck carcinoma: experience at the Gustave-Roussy Institute in a series of 169 patients.

PURPOSE: To review our experience using full-dose external reirradiation given with a curative intent for patients with unresectable head and neck carcinoma (HNC). PATIENTS AND METHODS: Between January 1980 and December 1996, 169 patients who presented with unresectable nonmetastatic HNC in a previously irradiated area were included in this series. The median time between the first and the second irradiation was 33 months. Reirradiation protocols were as follows: radiotherapy alone (65 Gy over 6.5 weeks at 2 Gy/d), 27 patients; Vokes protocol, ie, five to six cycles of radiotherapy (median total dose, 60 Gy; 2 Gy/d) with simultaneous fluorouracil (5-FU) and hydroxyurea, 106 patients; and bifractionated radiotherapy (median total dose, 60 Gy; 2 x 1.5 Gy/d) with concomitant mitomycin, 5-FU, and cisplatin, 36 patients. The median cumulative dose of the two irradiations was 120 Gy. Eighty-five percent of the tumors were squamous cell carcinoma, 14% undifferentiated carcinoma of nasopharyngeal type, and 1% adenocarcinoma. Forty-four percent were local recurrences, 23% nodal recurrences, 14% both local and nodal, and 19% second primary tumors. RESULTS: Mucositis grade 3 (World Health Organization [WHO]) was found in 32% and grade 4 in 14% of cases. Four patients presented with neutropenia or thrombocytopenia (grade 3 or 4 WHO). Late toxicities (> 6 months) were as follows: cervical fibrosis (grade 2 to 3 Radiation Therapy Oncology Group [RTOG]), 41%; mucosal necrosis, 21%; osteoradionecrosis, 8%; and trismus, 30%. Five patients died of carotid hemorrhage, apparently in complete remission. Six months after the onset of reirradiation, 37% of patients were in complete response. Patterns of failure were local only (53%), nodal only (20%), metastatic only (7%), and multiple (20%). Median follow-up time was 70 months. Overall survival rate (Kaplan-Meier) was 21% (95% confidence interval [CI], 15% to 29%) at 2 years and 9% (95% CI, 5% to 16%) at 5 years. Median survival time was 10 months for the entire population. Thirteen patients, of whom 12 were treated with the Vokes protocol, were long-term disease-free survivors. In a multivariate analysis, the volume of the second irradiation was the only factor significantly associated with the risk of death: relative risk=1.8 (95% CI, 1.13 to 5.7) (P=.01). CONCLUSION: Full-dose reirradiation combined with chemotherapy was feasible in patients with inoperable HNC. The incidence and severity of late toxicity was markedly increased in comparison to that observed after the first irradiation. Median survival was better than that generally obtained using palliative chemotherapy alone. A small proportion of patients were long-term disease-free survivors.

Aesthesioneuroblastoma.

Forty patients were treated or followed up for aesthesioneuroblastoma between 1980 and 1995 at Institut Gustave Roussy, France. There were three T1, seven T2, 15 T3 and 15 T4 lesions. The cervical metastatic rate at presentation was 18 per cent. Distant metastases were detected by bone marrow biopsy and bone scan in three patients at presentation. Treatment modalities included surgery alone in eight patients, radiotherapy alone in three patients, combined modality surgery plus radiotherapy in 11 patients, chemotherapy alone in two patients, chemotherapy plus radiotherapy in 10 patients, and multimodality therapy chemotherapy plus surgery plus radiotherapy in six patients. The five-year survival rate was 51 per cent. Multimodality treatment offered better survival (63 per cent at five years) and disease-free interval (54 months). Overall local, regional, and distant failure rates were 58 per cent, 15 per cent and 40 per cent respectively. Distant metastases commonly occurred in bone (82 per cent). Cervical metastasis was an unfavourable prognostic indicator (0 per cent survival at two years). In conclusion, aesthesioneuroblastoma is sensitive to chemotherapy and radiotherapy. Multimodality therapy should be used initially.