Multicenter prospective micro-costing study evaluating mandibular free-flap reconstruction.

Free-flap mandibular reconstruction is a highly specialized procedure associated with severe complications necessitating re-interventions and re-hospitalizations. This surgery is expensive in terms of health workers' time, equipment, medical devices and drugs. Our main objective was to assess the direct hospital cost generated by osseocutaneous free-flap surgery in a multicentric prospective micro-costing study. Direct medical costs evaluated from a hospital perspective were assessed using a micro-costing method from the first consultation with the surgeon until the patient returns home, thus confirming the success or failure of the free-flap procedure. The mean total cost for free-flap intervention was 34,009€ (5151-119,604€), the most expensive item being the duration of hospital bed occupation, representing 30-90% of the total cost. In the event of complications, the mean cost increased by 77.3%, due primarily to hospitalization in ICU and the conventional unit. This surgery is effective and provides good results but remains highly complex and costly.

Role of near-infrared fluorescence imaging in head and neck cancer surgery: from animal models to humans.

Complete resection of head and neck cancers with negative surgical margins improves the prognosis of the disease and decreases the recurrence rate. Near-infrared fluorescence-guided surgery of head and neck cancer is a rapidly evolving field that represents an invaluable tool for tumor detection and resection. Here, we present a literature review of the principles of near-infrared fluorescence imaging and its use in head and neck cancer surgery. We discuss important studies in both animal models and humans that have been carried out up to this point. We also outline the important fluorescent molecules and devices used in head and neck fluorescence imaging-guided surgery. Although near-infrared fluorescence-guided surgery for head and neck cancers showed efficacy in animal models, its use in humans is limited by the small number of fluorescent probes that are approved for clinical use. However, it is considered as a novel surgical aid that helps delineate tumor margins preoperatively and could spare patients from the added morbidity that is associated with additional surgery or chemoradiation. In addition, it is a useful tool to detect sentinel lymph nodes as well as metastatic lymph nodes.

Multicenter study to assess endoscopic resection of 159 sinonasal adenocarcinomas.

PURPOSE: This study was designed to assess the efficacy and morbidity of the endoscopic endonasal approach for the treatment of sinonasal adenocarcinomas. METHODS: This was a retrospective, multicenter study of nine French tertiary referral centers, including untreated patients. All patients were operated by an endoscopic approach. Tumors were classified according to the UICC 2002. Demographic, therapeutic, histological, morbidity data, and the course of the disease were recorded. Survival rates were obtained using the Kaplan-Meier method. RESULTS: A total of 159 patients were included with a mean age of 69 years. There were 19T1, 62T2 (1M1), 36T3 (1N1), 26T4a, and 16T4b (1N2a-1N2c). The mean duration of hospitalization was 4.4 days. The histologic outcomes showed that the olfactory cleft, the posterior and anterior ethmoid sinus, and the sphenoid, maxillary, and frontal sinuses were invaded in 95, 64, 55, 19, 7, and 3 % of cases, respectively. Histologic margins were positive in 17 % (1T1, 4T2, 3T3, 2T4a, and 8T4b). In total, 130 patients received adjuvant radiotherapy on the primary tumor site (58 Gy), 24 cases were not irradiated, and 5 refused treatment. The mean follow-up was 32.5 ± 24 months. The complication rate was 19 %: 6 epistaxis, 3 meningitis, 6 CSF leaks, 2 dacryocystitis, and 8 septoplasties. The recurrence rate was 17.6 % (28 cases) within 23 ± 21 months. Eleven patients underwent a second surgical procedure. Nine patients died of their disease (3T2, 2T3, 4T4b). The global and disease-specific, recurrence-free survival rate at 3 years was 74 and 84 % respectively. CONCLUSIONS: The endoscopic approach seems to be efficient to remove sinonasal adenocarcinoma with low morbidity.

[Pathologists and the French network of expertise on rare cancers ENT: The REFCORpath]. / Les pathologistes et le réseau d'expertise français sur les cancers ORL rares: le REFCORpath.

Aerodigestive tract tumors are very diverse, either in terms of location, or histologically. Also, this heterogeneity poses particular problems for the histological diagnosis but also for the establishment of the most appropriate treatment. Thus, the network REFCOR (réseau d'expertise français sur les cancers ORL rares/French expert network on rare ENT cancers) was created to better understand these issues, by proposing an epidemiological and diagnostic approach with research collaborations. This network is dedicated to all primary malignant tumors of the salivary glands, ear, nasal cavity and sinuses and all head and neck malignancies other than conventional squamous cell carcinoma. The REFCORpath network consists of expert pathologists and offers, through a network of scanned images, a second opinion or even a third.

Sphenoid sinus fungus ball.

The objective of this retrospective study is to present a large series of patients with sphenoid sinus fungus ball (SSFB) and describe clinical manifestations, diagnostic workup, surgical treatment, and eventual complications of this disease. We included patients operated on for this disease over a 14-year period. All patients benefited from mid-to-long-term follow-up. There were 28 patients (18 females, 10 males, mean age 64 years). Main symptoms were posterior rhinorrhea and headache. Less common symptoms were alteration of vision or ocular mobility and cacosmia. Preoperative diagnosis was based on nasal endoscopy and CT scanning. MRI was performed in case of suspicion of a tumor, an intraorbital or intracranial invasion. Treatment consisted in endoscopic transnasal or transethmoidal sphenoidotomy with removal of the fungus ball. Specimens were sent to pathology and mycology to confirm diagnosis. Postoperative complications consisted of two cases of epistaxis and two other cases of bacterial superinfection of the operated sphenoid cavity. No recurrence of the fungus ball was seen after a mean follow-up of 13 months. To conclude, SSFB is a relatively uncommon entity, usually due to Aspergillus infection. Although not invasive, if left untreated, it can lead to long-term serious complications. Preoperative nasal endoscopic examination and CT scan are the standard tools for diagnosis. Endoscopic sphenoidotomy with removal of the fungus ball is the current treatment because it has proven effective and has a low morbidity and recurrence rate.

Course and prognosis of basaloid squamous cell carcinoma of the head and neck: a case-control study of 62 patients.

OBJECTIVE: To describe the natural history and evaluate the prognosis of basaloid squamous cell carcinoma (BSCC) of the upper aero-digestive tract as compared to the usual squamous cell carcinoma (SCC). MATERIALS AND METHODS: Sixty-two patients with BSCC and 62 patients with SCC were matched with regards to TNM classification, localisation and therapeutic modalities. Histological criteria, follow-up and 5-year survival were compared among the two groups. RESULTS: Survival rates were significantly higher in patients with SCC as compared to patients with BSCC. The rate of distant metastasis was six times higher in cases of BSCC, which was the major cause of mortality. CONCLUSION: This study reveals that BSCC has distinct histo-pathologic features and an aggressive clinical course, justifying its consideration as a separate entity with poor prognosis. The authors propose to systematically perform a chest CT-scan and FDG-PET to rule out early distant metastasis and to include adjuvant chemotherapy in treatment protocols.

Tumor-specific methylation in saliva: a promising biomarker for early detection of head and neck cancer recurrence.

PURPOSE: Our goal was to define tumor and saliva gene methylation profile of head and neck squamous cell carcinoma and to evaluate its prognostic significance and its biomarker potential for early detection of relapse. EXPERIMENTAL DESIGN: We prospectively analyzed 11 genes by methylation-specific PCR on primary tumors, histologically normal adjacent mucosa, and saliva from 90 French patients at diagnosis and during follow-up as well as on 30 saliva specimens from control-matched patients with nonmalignant head and neck pathology. Five additional genes were analyzed on 50 tumors of the series. RESULTS: Methylation of TIMP3, ECAD, p16, MGMT, DAPK, and RASSF1 was the most frequently observed in tumors and paired saliva samples were analyzed at diagnosis, with an excellent agreement between both samples. At least one of these six genes was methylated in >75% of the samples without additional positive samples when other genes were analyzed. Methylation profile was similar in newly diagnosed and second primary cancers. Aberrant methylation was not associated with a worse prognosis. Ninety percent of normal adjacent mucosa and all control saliva samples were negative. Twenty-two patients were followed after treatment; abnormal methylation was detectable in the saliva of five patients few months before clinical and 2-deoxy-2[(18)F]fluoro-d-glucose-positron emission tomography signs of relapse, allowing curable surgery. Saliva samples were negative for the 17 other patients: 16 were in remission and only 1 relapsed. CONCLUSIONS: Gene methylation in saliva is a promising biomarker for the follow-up and early detection of still curable relapses of head and neck squamous cell carcinoma patients.

Cervical cellulitis and mediastinitis following esophageal perforation: a case report.

UNLABELLED: Chicken bone is one of the most frequent foreign bodies (FB) associated with upper esophageal perforation. Upper digestive tract penetrating FB may lead to life threatening complications and requires prompt management. We present the case of a 52-year-old man who sustained an upper esophageal perforation associated with cervical cellulitis and mediastinitis. Following CT-scan evidence of FB penetrating the esophagus, the impacted FB was successfully extracted under rigid esophagoscopy. Direct suture was required to close the esophageal perforation. Cervical and mediastinal drainage were made immediately. Naso-gastric tube decompression, broad-spectrum intravenous antibiotics, and parenteral hyperalimentation were administered for 10 d postoperatively. An esophagogram at d 10 revealed no leak at the repair site, and oral alimentation was successfully reinstituted. CONCLUSION: Rigid endoscope management of FB esophageal penetration is a simple, safe and effective procedure. Primary esophageal repair with drainage of all affected compartments are necessary to avoid life-threatening complications.

Adenocarcinoma of Ethmoid: a GETTEC retrospective multicenter study of 418 cases.

OBJECTIVE: To determine risk factors and evaluate the treatment of ethmoid adenocarcinoma. Epidemiologic data were recorded and compared with the literature. MATERIALS AND METHODS: A multicenter and retrospective study. The medical records of 418 patients who had presented with ethmoid adenocarcinoma at 11 French hospitals from 1976 to 2001 were analyzed to determine the clinical characteristics and treatment of the disease. RESULTS: The gender ratio was 2.8 men per 1 woman. Toxic exposure was classic for this lesion, exposure to wood and leather for most cases. The mean age was 63 years (range 31-91). Symptoms were nonspecific and based on clinical rhinologic signs. Nasal endoscopy after mucosal retraction was found useful to evaluate the extension of the lesion and to perform biopsies. Computed tomography scan and magnetic resonance imagery must be carried out prior to treatment to define extra nasal extension. The survival rate was significantly influenced by the size of the lesion (T4, N+) and extension to brain or dura. Surgery with postoperative radiotherapy remains the treatment of choice. Total excision must be a major priority, as confirmed in our series. CONCLUSION: This retrospective study was, to our knowledge, the largest ever reported in the literature. This series confirmed the risk factor of this lesion as well as the lesion's influence on the survival rate. Surgery is the most important part of the treatment. Local recurrences were responsible for the poor prognosis of this lesion.

Multicenter assessment of exclusive endoscopic endonasal approach for the treatment of 53 olfactory neuroblastomas.

BACKGROUND: Given the particularities of olfactory neuroblastoma (ONB) and the lack of studies on the subject, a multicenter collaborative study was conducted to assess treatment strategy. METHODS: Fifty-three patients with ONB were included from the French Rare Head and Neck Cancer Expert Network (REFCOR) database: 16T1, 8T2, 19T3, and 10T4. All cases were treated endoscopically with skull base removal and repair in 26 cases (49%) and without external craniotomy. RESULTS: The overall survival (OS) and disease-free survival (DFS) rates at 5 years were 87% and 71%, respectively, with mean follow-up of 45.4 ± 26.5 months. The complication rate was 18.8% with 4 cases of meningitis. Pathological analysis showed positive margins in 26.8%, notably on the dura-mater and periorbita, without impairment of OS or DFS. Forty-eight patients received adjuvant radiotherapy on T ± N. Ten patients had a recurrence (18.9%). Six patients died of their disease. Prophylactic neck irradiation seemed to reduce the recurrence rate. CONCLUSION: Exclusively endoscopic treatment proved efficient and reliable in a large controlled series.

What is the diagnostic value of flexible bronchoscopy in the initial investigation of children with suspected foreign body aspiration?

PURPOSE OF THE STUDY: The diagnosis and early bronchoscopic extraction of a foreign body (Fb) in children are life-saving measures. Many studies have described the manifestation of foreign body aspiration (FbA); however, only a few analyzed the role of flexible bronchoscopy in the diagnosis of FbA. The aim of this work is to define the indications of flexible bronchoscopy in the management algorithm of suspected FbA. SETTING: This study was conducted at a tertiary referral University Medical Center with an outpatient clinic and a 20-bed pediatric emergency unit. MATERIAL AND METHODS: Between January 2002 and July 2006 children referred with suspected FbA were included in this prospective study. Children with asphyxiating FbA requiring immediate rigid bronchoscopy, were excluded. If there was no convincing evidence of FbA, a diagnostic flexible bronchoscopy was performed under local anesthesia. In the case where a Fb was actually found, extraction was always performed by rigid bronchoscopy. RESULTS: Seventy cases (median age: 2 years, males: 44/females: 26) were analyzed. Among the 19 children who underwent flexible bronchoscopy first, 7 (37%) had a Fb. Among the 51 who underwent rigid bronchoscopy first, 43 had a Fb and 8 (16%) had a negative first rigid bronchoscopy. Predictive signs of a bronchial Fb were a radiopaque Fb, foreign body aspiration syndrome (FbAS) associated with unilaterally decreased breath sounds or localized wheezing and obstructive emphysema or atelectasis. CONCLUSION: In case of suspected FbA in children, the following management algorithm is suggested: rigid bronchoscopy should be performed solely in case of asphyxia, finding of a radiopaque Fb, or in the presence FbAS associated with unilaterally decreased breath sounds, localized wheezing and obstructive radiological emphysema, or atelectasis. In all other cases, flexible bronchoscopy should be performed first for diagnostic purposes.

Spontaneous Cerebrospinal Fluid Rhinorrhea: Association with Body Weight and Imaging Data.

Objective Spontaneous cerebrospinal fluid rhinorrhea (SCSFR) might be the only clinical manifestation of idiopathic intracranial hypertension (IIH), which has been historically related to overweight. Our goal was to search for an association between SCSFR and increased body weight on the one hand and SCSFR and imaging findings suggestive of IIH on the other hand. Materials and Methods We retrospectively collected clinical and radiological data of patients operated on endoscopically for SCSFR in our institution from 1993 to 2013. Analyzed factors were body mass index (BMI), extended sphenoid sinus pneumatization on computed tomography, and empty sella and distention of the optic nerve sheath on magnetic resonance imaging. Results There were 15 patients: 8 females/7 males; mean age 50 years. Primary surgical success rate was 86.7%. Regarding body weight, 80% were overweight (BMI ≥ 25) versus 32% in the French general population ( p < 0.001). Among patients with SCSFR, 20% were obese (BMI ≥ 30) versus 15% in French individuals without SCSFR ( p = 0.483). Increased pneumatization of sphenoid sinuses was observed in 92.9 versus 27.5% in the general population ( p < 0.0001). Empty sella was found in 46.2 versus 3% in the general population ( p < 0.00001). Dilation of the optic nerve sheath was observed in 46.2 versus 15% in the general population ( p < 0.01). Conclusion We found statistically significant associations between SCSFR and overweight, increased pneumatization of sphenoid sinuses, empty sella, and dilation of optic nerve sheath, but not with obesity, which did not have any additional impact of CSF leak than did overweight.

Epistaxis and its management: an observational pilot study carried out in 23 hospital centres in France.

OBJECTIVE: The purpose of this study is to describe the treatment of epistaxis in hospital emergency departments and to identify the principal risk factors for more severe episodes of bleeding. STUDY PROTOCOL: Prospective cross-sectional epidemiological study MATERIAL AND METHODS: This study was carried out in 23 hospital centres in France, most of them teaching hospitals. Every patient presenting non-traumatic epistaxis or else associated with hereditary hemangioma during two consecutive and separate 24-hour periods were included. RESULTS: Fifty patients were included in the study. Nasal bleeding was stopped within 30 minutes for 47 patients. Fourteen patients were hospitalized. The risk factors for severe epistaxis included either copious bleeding or else bleeding for more than 6 hours or patients aged 65 and over. A history of repeated nasal packing and/or taking medication with a known hemorrhagic risk was associated with the amount and duration of bleeding (p < 0.05). CONCLUSION: Risk factors for severe epistaxis should be identified as to improve patient care and avoid treatment failure or useless hospitalization.

Near-infrared fluorescence imaging-guided surgery improves recurrence-free survival rate in novel orthotopic animal model of head and neck squamous cell carcinoma.

BACKGROUND: Appropriate animal models are required to test novel therapeutics for head and neck squamous cell carcinoma (HNSCC) such as near-infrared (NIR) imaging-guided surgery. METHODS: We developed an optimized animal model of orthotopic HNSCC (in female athymic NMRI (Naval Medical Research Institute) nude mice) with a prolonged survival time. Resection of the orthotopic tumors was performed 30 days after implantation with or without the aid of a miniaturized clinical grade NIR optical imaging device, after systemic administration of a fluorescent RGD-based probe that targets αv ß3 integrin. RESULTS: NIR optical imaging-guided surgery increased the recurrence-free survival rate by 50% through the detection of fluorescent cancer residues as small as 185 µm; these fragments could remain unidentified if resection was performed exclusively under unaided visual guidance. CONCLUSION: NIR optical imaging-guided surgery showed an improved HNSCC tumor resection quality in our optimized orthotopic animal model. © 2015 Wiley Periodicals, Inc. Head Neck 38: E246-E255, 2016.

Chronic hypoxia protects against gamma-irradiation-induced apoptosis by inducing bcl-2 up-regulation and inhibiting mitochondrial translocation and conformational change of bax protein.

Malignant tumours contain zones of chronic or acute hypoxia, which influence their prognosis and progression. The goal of our study was to understand the role of hypoxia in radio-resistance in a squamous cell carcinoma cell line of the head and neck (KB-3-1 cells). Cell growth was evaluated by Trypan blue exclusion under chronic hypoxia (3-5% O2) for 4 weeks or under normal conditions (21% O2). Cells were then gamma-irradiated either by X-ray (2-6 Gy) or UV-C radiation (0.001-10 J/cm(2)). Apoptosis was estimated by double staining with orange acridine and ethydium bromide and fluorescence microscopy. DNA content was estimated by FACS analysis. Expression of Bax, Bcl-2 and P53 was assessed by immunofluorescence and Western blotting. ROS production was measured by dichlorofluorescein fluorescence. Cell growth depends on oxygen tension. It decreased by 42 and 70% at 5 and 3% O2 compared to control with a significant cell cycle arrest rather than increased mortality. Hypoxic cells are more radio-resistant (x2.5) than normoxic cells. Under chronic hypoxia, Bcl-2 increased considerably in cells compared to control, while Bax and P53 did not change. After irradiation, in hypoxic cells very weak expression of the pro-apoptotic Bax protein and no translocation of Bax to the mitochondria were observed. In addition, irradiation of control KB-3-1 cells demonstrated a large increase in ROS production (x2) compared to cells irradiated identically under hypoxia. In conclusion, chronic hypoxia: i) seems to slow-down cell growth of KB-3-1 cells without inducing apoptosis, ii) induces Bcl-2 overexpression and prevents radiation-induced apoptosis by inhibiting ROS production and altering Bax subcellular redistribution and conformational changes.

Malakoplakia of the neck.

Malakoplakia that presents in the head and neck is very rare. We describe a 76-year-old man who presented with an inflammatory mass in the lateral aspect of the neck that clinically mimicked a tumoral expansion and was consistent with a cervical malakoplakia. To our knowledge, this is the second case reported with manifestations of this chronic inflammatory disease localized in the neck. Malakoplakia is a rare granulomatous disease that most frequently involves the genitourinary tract and occurs in an immunodeficient host. The symptoms are nonspecific and the diagnosis is based on the histologic findings. In the present case, the biopsy specimen of the cervical mass revealed a collection of numerous von Hansemann cells containing Michaelis-Gutmann bodies, which are pathognomonic of malakoplakia. Bacteriologic analysis identified Escherichia coli. The evolution was favorable after surgical excision and prolonged antibiotic therapy with fluoroquinolones.

[2003 Update of Standards, Options and Recommendations for management of patients with salivary gland malignant tumors (excluding lymphoma, sarcoma and melanoma) (summary report)]. / Standards, Options et Recommations 2003 pour la prise en charge des patients atteints de tumeurs malignes des glandes salivaires (lymphomes, sarcomes et mélanomes exclus), mise à jour (rapport abrégé).

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVES: To update clinical practice guidelines for the management of patients with salivary gland malignant tumors previously validated in 1997. These recommendations cover diagnosis, classification, treatment and follow-up of patients with these tumors. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPG s according to the definitions of the Standards, Options and Recommendations project. Once the guidelines has been defined, the document is submitted for review by independent reviewers. RESULTS: This article is a summary version of the full document presenting the updated clinical practice guidelines with algorithms. The main questions addressed by the expert group in this update concern the place of fine needle aspiration biopsy in preoperative diagnosis, the place of cervical lymph node area surgical treatment, the place of postoperative irradiation and neutron therapy in the treatment of unresectable tumors and also the place of medical imaging, especially RMI, for the diagnosis of these tumors.

[Rare tumors of the head and neck; on behalf of the REFCOR, the French Network of rare head and neck tumors]. / Cancers ORL rares et REFCOR, Réseau d'expertise français sur les cancers ORL rares.

Malignant tumors of the upper aerodigestive tract may be rare by their histology (sarcoma, variants of conventional squamous cell carcinomas) and/or location (sinuses, salivary glands, ear, of various histologies themselves). They represent less than 10% of head and neck neoplasms. The confirmation of their diagnosis often requires a medical expertise and sometimes biomolecular techniques complementary to classical histology and immunohistochemistry. Due to their location, their treatment often requires a specific surgical technique. Radiation therapy is indicated based on histoclinical characteristics common to other head and neck neoplasms but also incorporate grade. Further, the technique must often be adapted to take into account the proximity of organs at risk. For most histologies, chemotherapy is relatively inefficient but current molecular advances may allow to consider pharmaceutical developments in the coming years. The REFCOR, the French Network of head and neck cancers aims to organize and promote the optimal management of these rare and heterogeneous diseases, to promote research and clinical trials.

Lemierre syndrome: study of 11 cases and literature review.

BACKGROUND: Lemierre syndrome is a rare but serious illness that associates throat infection and thrombosis of the internal jugular vein (IJV) or one of its tributaries with subsequent distant septic emboli. The purpose of our study was to review the pathogenesis, clinical presentation, and treatment of this disease. METHODS: Patients with confirmed Lemierre syndrome were included in our retrospective monocentric study. All patients had bacteriologic analyses as well as radiologic imaging. RESULTS: There were 11 patients in our study (from 1998-2012). Fusobacterium necrophorum was responsible for the infection in 45% of cases. Surgical drainage of pharyngeal, cervical, or mediastinal abscesses was carried out in 8 cases. All patients received broad-spectrum antibiotics. Six patients were admitted to the intensive care unit (ICU). One patient (9%) died. CONCLUSION: Treatment with broad-spectrum antibiotics is the primary choice of treatment of Lemierre syndrome. Surgery is indicated in case of abscess formation.

A rationale for chemoradiation (vs radiotherapy) in salivary gland cancers? On behalf of the REFCOR (French rare head and neck cancer network).

BACKGROUND: Salivary gland carcinomas constitute a heterogeneous group of tumors, with over 20 histological subtypes of various prognoses. The mainstay of treatment is surgery, with radiotherapy advocated for unresectable disease or postoperatively in case of poor prognostic factors such as high grade, locally advanced and/or incompletely resected tumors. Concurrent chemotherapy is sometimes advocated in routine practice based on criteria extrapolated from squamous cell carcinomas of the head and neck, on radioresistance of salivary gland tumors and on results obtained in the metastatic setting. The aim of this review was to identify situations where chemotherapy is advocated. MATERIAL AND METHODS: A search of literature was performed with the following key words: parotid, salivary gland, neoplasm, cancer, malignant tumor, chemoradiation, chemotherapy, radiotherapy and treatment. Case report and studies published before 2000 were not included. RESULTS: Platinum-based regimens were the most frequent. Other regimens were reported and seemed dependent on histology. The level of evidence for the concurrent delivery of chemotherapy with radiation therapy is supported by a low level of evidence. Prescribing chemotherapy mostly relies on poor prognostic factors similar to those used to indicate high dose radiotherapy. Protocols vary with histology. CONCLUSION: The rationale for adding chemotherapy to radiotherapy remains to be demonstrated prospectively. Although the type of systemic treatments used may be adapted on histology, the strongest rationale remains in favor of cisplatin.