Impact of extensive surgery in multidisciplinary approach of pterygopalatine/infratemporal fossa soft tissue sarcoma.

BACKGROUND: To evaluate a strategy whereby extensive surgery ± external radiotherapy (RT) could improve local control in pterygopalatine/infratemporal fossa (PIF) sarcoma. PROCEDURE: Forty-one patients with a diagnosis of sarcoma involving the PIF and referred to our Institute from 1984 to 2009 were included in the analysis. Patients received multidrug chemotherapy and radiotherapy ± surgery, depending on the period of treatment. RESULTS: The median age at diagnosis was 7.6 years (range: 0.1-22 years). There were 36 RMS, 3 undifferentiated sarcoma and 2 other soft-tissue sarcomas. Sixty-eight percent of patients had meningeal risk factors at diagnosis. Local treatment consisted of RT alone in 19 patients, surgery in combination to RT in 19 patients and surgery alone in 3 patients. The local progression rate (LPR) at 5 years was 45% for the entire population, 59% for the 19 patients treated with RT alone and 34% for the 22 patients who had surgery as part of their treatment. All locoregional failures after extensive surgery occurred at the skull base and/or in leptomeningeal spaces. CONCLUSIONS: Multidisciplinary approach including extensive surgery for PIF sarcoma is feasible and yields good local control with 15/22 patients in local complete remission. Future studies are warranted to confirm these promising results, to evaluate the possibility of avoiding RT or limiting the RT field, and to extend the indication for extensive surgery to other "worse" sites of PM sarcoma such as the paranasal sinuses.

Sudden death after major head and neck surgery.

PURPOSE OF REVIEW: This review will discuss the mortality after major ear, nose and throat surgery, particularly sudden death. It will also discuss the postoperative follow-up of patients. RECENT FINDINGS: Sudden death is a rare event after major ear, nose and throat surgery, and occurs mainly during the first three postoperative days. SUMMARY: In more recent studies, the mortality rate after neck dissection was below 4%, which is at a lower value than reported in previous studies. Sudden deaths have been described, however, mainly during the first three postoperative days. Alcoholism and perioperative hypotension are two predictive factors for cardiac complications. Careful follow-up of these patients during the early postoperative period should be performed to reduce the mortality by shortening the delay of care.

Functional results with advanced hypopharyngeal carcinoma treated with circular near-total pharyngolaryngectomy and jejunal free-flap repair.

BACKGROUND: Patients treated by a circular pharyngolaryngectomy for advanced hypopharyngeal carcinoma have a poor prognosis and disappointing speech restoration. METHODS: Three carefully selected patients underwent a near-total laryngectomy circular pharyngectomy with jejunal free flap repair and dynamic tracheopharyngeal shunt for treatment of advanced hypopharyngeal carcinoma. They received induction chemotherapy and postoperative radiotherapy. We assessed the functional outcome. RESULTS: There was no major local complication. One year after the end of radiotherapy, all patients were able to eat solid diets. Two patients were able to speak immediately after the end of the treatment. After speech re-education, a high-quality tracheopharyngeal voice was restored in all three patients. Performance Status Scale for Head and Neck Cancer Patients (PSSHN) showed a mean score equal to 81/100 at 1 year. CONCLUSIONS: In selected patients, near-total laryngectomy circular pharyngectomy with tracheopharyngeal shunt and jejunal free-flap repair offers good voice rehabilitation without impairing swallowing function.

Salvage surgery after failure of very accelerated radiotherapy in advanced head-and-neck squamous cell carcinoma.

PURPOSE: To assess the efficacy and toxicity of salvage surgery for local or cervical nodal recurrence after accelerated radiotherapy for locally advanced head-and-neck squamous cell carcinoma (HNSCC). METHODS AND MATERIALS: We reviewed the medical records of the 136 patients with HNSCC who had been treated in three consecutive clinical trials at the Institut Gustave-Roussy using a very accelerated radiotherapy regimen (62 to 64 Gy with 2 daily fractions of 1.8 to 2 Gy over 3.5 weeks). Sixty-nine patients of the 136 initial patients (51%) had local or neck lymph nodes relapse, or both. RESULTS: Sixteen of these 69 patients (23%) had undergone salvage surgery for recurrence locally (n = 8) or in the cervical nodes (n = 8). All 16 had initially been diagnosed with locally advanced oropharyngeal carcinoma (T4, 11 patients; T3, 5 patients), and 13 had initially had cervical node involvement. After salvage surgery, 6 patients had had a local recurrence; 7, cervical node recurrence; and 3, distant metastasis. Thus, salvage surgery had been successful only in 3 patients. The 3- and 5-year overall actuarial survival rates were 20% and 11%, respectively. Eight patients had major postoperative wound complications, including carotid rupture in three cases. CONCLUSION: Salvage surgery for relapse after very accelerated radiotherapy for advanced HNSCC is infrequently feasible and is of limited survival benefit. It should be used only in carefully selected cases.

Treatment of the N0 neck during salvage surgery after radiotherapy of head and neck squamous cell carcinoma.

BACKGROUND: The morbidity and mortality rates of salvage surgery in patients with local recurrence of head and neck squamous cell carcinoma (HNSCC) after radiotherapy are high. The aim of this study was to determine the rate of occult neck node metastasis and the surgical morbidity of patients after salvage surgery for local relapse after definitive radiotherapy. METHODS: Thirty patients who underwent salvage surgery with a simultaneous neck node dissection for a local relapse after definitive radiotherapy for HNSCC between 1992 and 2000 were included in this study. The primary tumor sites were oral cavity in six patients, oropharynx in 17, supraglottic larynx in three, and hypopharynx in four. Initially, seven patients had T2 disease, eight had T3, and 15 had T4. RESULTS: Twelve patients (40%) experienced postoperative complications, including two deaths. There was no cervical lymph node metastasis (pN0) in 29 of the 30 patients. Fifteen patients (50%) had a recurrence after salvage surgery, including 11 new local recurrences and four patients with distant metastasis. CONCLUSIONS: The risk of neck node metastasis during salvage surgery for local recurrence in patients treated initially with radiation for N0 HNSCC is low. Neck dissection should be performed in only limited area, depending on the surgical procedure used for tumor resection.

Molecular detection of early-stage laryngopharyngeal squamous cell carcinomas.

PURPOSE: We sought to determine whether early-stage laryngopharyngeal squamous cell carcinomas (SCC) can be detected through molecular analysis of exfoliated cells collected with the use of a pharyngoesophageal brush (PEB). EXPERIMENTAL DESIGN: Thirty-three patients with a single, untreated, early-stage (T1 or T2) SCC of the supraglottic larynx or pharynx underwent collection of cells with a PEB, followed by endoscopic biopsy of the tumor. PEB specimens were also collected from five healthy subjects. PEB samples and tumor tissue were examined for hypermethylation of p16INK4a (CDKN2) gene promoter CpG islands (assayed by methylation-specific PCR) and UT5085 tetranucleotide microsatellite instability (assayed by GeneScan analysis). PEB samples were also subjected to cytologic analysis. RESULTS: Eight of 33 (24%) tumors exhibited a bandshift at UT5085, and 14 of 33 (42%) exhibited hypermethylation at the p16 promoter. Overall, 17 of 33 (52%) patients had at least one of the two markers in their tumor. Cytologic analysis of PEB samples revealed tumor in 4 of 33 (12%) patients; cytologic findings were normal in all five control subjects. Molecular analysis of PEB samples revealed tumor DNA in 13 of 17 (76%) patients with at least one of the two molecular markers in their tumor. Eight of 14 (57%) patients with p16 hypermethylation in their tumor and 8 of 8 (100%) patients with UT5085 microsatellite instability in their tumor had similar findings in the PEB samples. None of the PEB samples from the control subjects or patients with neither molecular marker in their tumor displayed abnormality. CONCLUSION: Molecular analysis of PEB samples holds promise for the early detection of early-stage laryngopharyngeal SCCs. New molecular markers need to be identified to increase the sensitivity of molecular screening.

Management of advanced and recurrent squamous cell carcinoma of the inner nasal lining.

UNLABELLED: Ten cases of advanced and eight cases of recurrent carcinomas of the inner nasal lining were managed in our department between June 1996 and June 2003. Six tumours were managed by operation alone, four by a combination of operation and radiotherapy, two by a combination of chemotherapy and operation, and five by a combination of chemotherapy, operation and radiotherapy. One patient died before the end of treatment. One patient had a combination of chemotherapy and radiotherapy. Eleven patients had reconstructions. RESULTS: After a mean follow up of 2.7 years (range: 3 months to 7 years), 15 patients were disease-free. Two patients had died of their disease, and one had died of an unrelated cause. Reconstruction was satisfactory in six of the eight cases that were evaluated. Prostheses were satisfactory in four of six cases.

Preoperative sequential chemotherapy in locally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: Induction chemotherapy may contribute to decreased local and distant recurrences in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) resectable for cure. METHODS: Patients with previously untreated locally advanced stage III-IV (N0-2, M0) SCCHN received a dose-dense sequential regimen combining cisplatin/5-fluorouracil followed by bleomycin/methotrexate/hydroxyurea. Induction chemotherapy was followed by locoregional surgery and/or radiation therapy. RESULTS: Among 37 patients, 23 (62%) had T4 primary tumors. Grade 3 to 4 asymptomatic hematologic toxicity occurred in less than 15% of patients. Nonhematologic toxicities were limited to grade 1 to 2 in less than 20% of patients. In the overall cohort (intent-to-treat; n = 35), 24 (68.5%) of 35 patients had objective clinical responses, including nine complete responses (25.7%). Fifty-seven percent of patients were free of disease at 2.5 years. CONCLUSIONS: Sequential induction chemotherapy is feasible and active in patients with locally advanced head and neck cancers and may further include recent compounds such as taxanes.

Postoperative radiotherapy for primary mucosal melanoma of the head and neck.

BACKGROUND: Primary head and neck mucosal melanoma (HNMM) has a poor prognosis with a low local control rate and frequent distant metastases. The objective of the current study was to determine the impact of postoperative radiotherapy on local control and survival. METHODS: One hundred forty-two patients with primary HNMM treated between 1979 and 1997 were reviewed. Of these, 69 patients with confirmed primary mucosal melanoma, absence of metastatic disease, and definitive management by surgery with or without postoperative radiotherapy and follow-up at the Institut Gustave-Roussy (Villejuif) were selected. The site of primary HNMM was sinonasal in 46 patients, oral in 19 patients, and pharyngolaryngeal in 4 patients. Twenty-two patients (32%) had a locally advanced tumor (T3-T4) and 17 patients had regional lymph node metastases after pathologic examination (pN > 0). Thirty patients underwent surgery alone and 39 received postoperative radiotherapy. Patients with locally advanced tumors had received postoperative radiotherapy more frequently than those with small tumors (P = 0.02). RESULTS: Thirty-seven patients (54%) experienced local disease recurrence and 47 patients (68%) developed distant metastasis. The overall survival rates were 47% at 2 years and 20% at 5 years. In the Cox multivariate analysis, patients with early T-classification tumors who received postoperative radiotherapy had a better local disease-free survival (P = 0.004 and P = 0.05, respectively) compared with patients with late T-classification tumors who did not receive postoperative radiotherapy. Patients with advanced T-classification and pN > 0 stage had a shorter distant metastasis disease-free survival compared with patients with early T-classification and pN < 0 stage. Patients with advanced T-classification tumors had a shorter overall survival compared with patients with early T-classification tumors (P = 0.003). CONCLUSIONS: The prognosis of patients with HNMM was poor. Patients had a high rate of distant metastasis and a low rate of local control. The current study suggested that postoperative radiotherapy increased local control even for patients with small tumors.

Locoregional effects of pegylated liposomal doxorubicin (Caelyx) in irradiated area: a phase I-II study in patients with recurrent squamous cell carcinoma of the head and neck.

Aim of this study was to determine the antitumour activity and toxicity of pegylated liposomal doxorubicin (Caelyx) in pretreated patients with locally recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). Caelyx was administrated as 1 h infusion every 3 weeks at doses of 35 mg/m2 (group A) and then subsequently given at 45 mg/m2 (group B). 26 patients received a total of 87 cycles. The median number of cycles was 3 (range 1-7). Four out of 24 evaluable patients (17%, 95% confidence interval (CI) 0.5-32%) showed significant evidence of antitumour activity, with tumour necrosis being observed in 2 patients. Grade 3-4 neutropenia was observed in only 2 patients. There were no grade 3-4 mucosal, skin, digestive, cardiac or hepatic toxicities. Caelyx has activity against locally recurrent SCCHN and is well tolerated up to 45 mg/m2, but a careful utilisation of this drug is required for tumours relapsing in irradiated areas.

Tetranucleotide microsatellite instability in surgical margins for prediction of local recurrence of head and neck squamous cell carcinoma.

PURPOSE: Postoperative radiotherapy is used to prevent local recurrence of head and neck squamous cell carcinoma in patients with positive surgical margins. We sought to determine whether tetranucleotide microsatellite instability could be detected in surgical margins and used to predict local recurrence. EXPERIMENTAL DESIGN: We prospectively collected tumor and surgical margin specimens from patients with head and neck squamous cell carcinoma who had undergone surgical resection at Institut Gustave-Roussy during a 1-year period. Margins were considered positive if extensive pathological examination revealed either carcinoma within 5 mm or dysplasia. We tested five tetranucleotide microsatellite markers (UT5085, L17686, D9S753, ACTBP2, and CSF1R) in the tumor specimens and paired surgical margins of the patients whose margins were negative on pathological examination. RESULTS: Pathological examination revealed that among the 76 patients, 22 had positive margins; therefore, these patients were excluded. Of the 54 remaining patients, 26 (48%) had tumors informative for markers UT5085, L17686, or both; the other 3 markers were not informative. Seven (27%) of the 26 informative tumors had the same instability pattern in the surgical margins. At a median follow-up of 26 months, 5 of the 7 local recurrences occurred in patients with molecularly positive surgical margins. A strong, independent association was found between positive surgical margins and local recurrence (P = 0.01; hazard ratio, 6.49). CONCLUSIONS: Tetranucleotide microsatellite instability in surgical margins may be a useful biomarker to predict local recurrence of head and neck squamous cell carcinoma in patients with apparently disease-free margins.

Morphologic parameters of normal swallowing events using single-shot fast spin echo dynamic MRI.

This study was designed to determine visible and measurable morphological parameters in normal swallowing using dynamic MRI with single-shot fast spin echo (SSFSE), as a preliminary study in view of noninvasive MRI swallowing evaluation in patients with dysphagia. Seven healthy volunteers aged 24-40 underwent dynamic MRI with SSFSE, with a 1.5-T unit, using a head and neck antenna. Patients repeated dry swallow, water swallow, marshmallow swallow, cake swallow, and cookie chewing for a total of five series, with 15 acquisitions per series at a rate of 700 ms per acquisition. A checklist of swallowing events and anatomic landmarks was used to determine which anatomic landmarks are always visible, which phases or swallowing movements are always visible, and which landmarks can be used to measure oral and pharyngeal motion in swallowing. The oral preparatory, oral, and oropharyngeal phases of deglutition were visible in all cases. No aspiration, reflux, or abnormal residue was observed. Spatial resolution allowed for anatomical measurements of laryngeal elevation, oropharyngeal diameter, and tongue base and velum displacement in all cases. SSFSE dynamic MRI is pertinent for evaluation of the anatomical and physiological characteristics of swallow. The temporal parameters, however, cannot be studied using this technique. Motion artifacts preclude its use in the study of mastication. It remains complementary to videofluoroscopy and other techniques in swallow evaluation.

Autofluorescence videoendoscopy for photodiagnosis of head and neck squamous cell carcinoma.

The diagnosis of head and neck squamous cell carcinoma is usually made by visual identification. Searching for a non-invasive optical diagnostic method with the ability to detect the precancerous lesions or second primary tumors earlier in high-risk populations led to the development of photodiagnosis by autofluorescence (AF) endoscopy. The aim of the present study was to evaluate and discuss the diagnostic potential of autofluorescence videoendoscopy as a complementary visual aid in the routine endoscopic diagnosis of head and neck cancers. In a prospective study, 48 patients underwent white light (WL) videoendoscopy followed by AF technique at the Institute of Gustave-Roussy from November 2001 to August 2002. Of 48 patients, 30 had suspected precancerous or cancerous laryngeal lesions, 7 presented benign laryngeal lesions, while 8 showed pharyngeal and 3 oral tumors. All detected lesions were evaluated by histological examination. AF was induced by filtered blue light of a xenon short arc lamp and processed by a CCD camera system (D-Light AF System; Storz, Tuttlingen, Germany). Normal laryngeal mucosa displayed a typical green fluorescence signal. Moderate and severe epithelial dysplasia, carcinoma in situ and invasive carcinoma showed a diminished green fluorescence and presented a marked reddish-blue color. In case of hyperkeratosis a bright white color was detected. Some benign lesions, such as granulomas, polyps and papillomas also displayed altered green fluorescence. Autofluorescence videoendoscopy for photodiagnosis of head and neck squamous cell carcinomas has proved to be a method of high specificity and good sensitivity. Two additional precancerous lesions that were invisible at the WL examination but detected with the AF technique show its potential role in the regular screening procedure or follow-up examination in a high-risk population. It was a very helpful complementary visual aid for the intraoperative control of the surgical margins after per oral endoscopic resection.

[Cervical cystic lymph-node metastases from epidermoid carcinoma]. / Les métastases ganglionnaires cervicales kystiques de carcinome épidermoïde.

Fifty-three cases of cystic nodal neck metastasis from squamous cell carcinoma were treated at the Institut Gustave Roussy over a 30 year period. In all cases the lesion presented as a cystic neck tumor with malignant cells found in the cyst wall on pathologic examination. A detailed physical examination of the upper aerodigestive tract mucosa revealed a small tumor located in Waldeyer's ring and often in the tonsil. Treatment consists of surgical resection of the tumor followed by external beam radiation therapy centered on the cervical lymph nodes and Waldeyer's ring. Prognosis is good, with 5-year actuarial overall survival rate of 77%.

T2 laryngeal carcinoma with impaired mobility: subtypes with therapeutic implications.

The aim of this study was to evaluate the outcome in the treatment of T2 laryngeal carcinoma with impaired laryngeal mobility, comparing surgical management to radiotherapy in terms of local control and survival. The files of 66 patients treated between 1988 and 1994 were retrospectively studied for tumor location, treatment and outcome. Forty-two patients were treated surgically and 24 by radiotherapy. Follow-up averaged 8.5 years. Local recurrence occurred in 12.5% of the cases treated by conservation laryngeal surgery and in 21% of the cases by radiotherapy. Ultimate laryngeal preservation was achieved in 90.9% of the cases initially treated by partial laryngectomy and in 87.5% of the cases treated by radiotherapy. Five-year actuarial survival rates were 90% and 28%, respectively. A higher rate of metastases and second primaries occurred in the group treated by radiotherapy. T2 laryngeal carcinoma amenable to partial laryngectomy had a higher local control rate than the cases not amenable to conservation surgery and treated by radiotherapy. Tumors differed in the two treatment groups in location and extensions, despite the fact that all were T2 tumors. We emphasize the limits of retrospective studies. Only prospective randomized studies will determine the true results of surgery versus radiotherapy for a homogeneous subset of T2 laryngeal tumors.