P. Marandas

Cervico-facial adenoid cystic carcinoma: Study of 102 cases. Influence of radiation therapy

One hundred two patients with cervico-facial adenoid cystic carcinoma were treated with surgery alone, radiotherapy alone or both from 1951 to 1980. All the cases have a 5-year minimum follow-up. The local control rate is 55.5% at 5 years and 37.7% at 10 years. The 5-year local control rate is 44% with surgery alone, 65.8% with radiotherapy alone and 77.8% with post-operative radiotherapy. The difference between surgery alone and radiosurgical association is significant (p less than 0.01). The bone involvement diminished local control rate (32.2%/k 68.8%). The 5-year survival rate of the patients who recurred and have been retreated is 70.5%. The 5-year survival rate of the patients after the appearance of a metastasis is 38.1% and 2 patients have survived more than 10 years. The NED 5-year survival rate is 48.8%. There is no significant difference in the NED 5-year survival rate according to sites or treatments. The crude 5-year survival rate is 70%, 51.4% at 10 years and 32.2% at 15 years. Our study shows that adenoid cystic carcinoma have a peculiar and slow evolution. Surgery with post-operative radiotherapy obtains the best local control. These results and the radiosensibility of these lesions allow us to propose an aggressive treatment for the recurrence and the primary tumor of the directly metastatic patients.

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.

Analysis of p53 Serum Antibodies in Patients With Head and Neck Squamous Cell Carcinoma

BACKGROUND Mutation of the p53 tumor suppressor gene (also known as TP53) often leads to the synthesis of p53 protein that has a longer than normal half-life. Mutant p53 protein that accumulates in tumor cell nuclei can be detected by means of immunohistochemical staining techniques. Serum antibodies directed against p53 protein (p53-Abs) have been detected in some cancer patients. PURPOSE We assayed serum samples from 80 patients with head and neck squamous cell carcinoma (HNSCC) for the presence of p53-Abs, and we evaluated potential associations between the presence of these antibodies and other histopathologic and clinical features. METHODS Serum was collected from each patient at the time of diagnosis. In addition, tumor biopsy specimens were obtained before the initiation of treatment. An enzyme-linked immunosorbent assay was used to detect p53-Abs. The accumulation of p53 protein in tumor cell nuclei was assessed immunohistochemically by use of the anti-p53 monoclonal antibody DO7. Patient treatment consisted of radiotherapy alone, primary chemotherapy followed by radiotherapy, or surgery and postoperative radiotherapy. Relapse-free and overall survival from the beginning of treatment were estimated by use of the Kaplan-Meier method; survival comparisons were made by use of the logrank statistic. Univariate and multivariate analyses were conducted to identify factors associated with survival. Reported P values are two-sided. RESULTS Fifteen (18.8%) of the 80 patients had p53-Abs. Tumor cell nuclei in 43 (58.9%) of 73 assessable biopsy specimens exhibited strong p53 immunostaining. Patient treatment method and the accumulation of p53 protein in tumor cell nuclei were not associated with increased risks of relapse or death. In univariate analyses, advanced tumor stage (> T1 [TNM classification]) and the presence of p53-Abs were significantly associated with an increased risk of death (P for trend = .007 and P = .002, respectively), whereas advanced tumor stage, substantial regional lymph node involvement (> N1), and the presence of p53-Abs were associated with an increased risk of relapse (P for trend = .002, P = .02, and P < .0001, respectively). In multivariate analyses, advanced tumor stage and the presence of p53-Abs were significantly associated with increased risks of relapse (p for trend = .04 and P = .003, respectively) and death (P for trend = .04 and P = .03, respectively). At 2 years of follow-up, the overall survival proportion was 63% (95% confidence interval [CI] = 47%-80%) when no p53-Abs were detected compared with 29% (95% CI = 4%-54%) when p53-Abs were detected. Relapse-free survival at 2 years was 62% (95% CI = 49%-76%) if no p53-Abs were detected compared with 13% (95% CI = 0%-31%) if p53-Abs were detected. CONCLUSIONS AND IMPLICATIONS The proportion of patients with HNSCC who have serum p53-Abs is smaller than that of patients exhibiting tumor cell accumulation of p53 protein. The presence of p53-Abs is significantly associated with increased risks of relapse and death.

Reconstruction with Free Jejunal Autograft after Circumferential Pharyngolaryngectomy: Eighty-Three Cases

The free jejunal autograft (FJA) has become a common procedure for pharyngeal reconstruction after circumferential pharyngolaryngectomy. In order to evaluate the postoperative outcome and the functional and carcinologic results, we retrospectively reviewed 83 cases of reconstruction with FJA. Fifty-one patients had received no prior radiotherapy, and 25 had received prior radiotherapy for their hypopharyngeal tumor or for another previous primary. Seven patients underwent a secondary reconstruction. In the postoperative course, there were 2 postoperative deaths, 4 graft failures (5%), and 11 salivary fistulas. The median time to removal of the nasogastric tube was 16 days, and to discharge, 23 days. Forty-eight patients received postoperative radiotherapy, with good tolerance. At 1 year postoperatively, 98% of the patients were able to eat a solid or soft diet. The postoperative radiotherapy did not impair the quality of the functional results in a long-term assessment. The vocal results were disappointing. The 3-year survival rate was 40%. The main carcinologic failures (45 patients) were locoregional recurrences (20 patients) and metastasis, which was the cause of death in 34% of the cases. It seems clear that FJA allows one-stage reconstruction and good swallowing rehabilitation, tolerates postoperative radiotherapy, and increases the quality of life in these patients with a poor prognosis.

Potential doubling time and clinical outcome in head and neck squamous cell carcinoma treated with 70 GY in 7 weeks

PURPOSE To study the predictive value of pretreatment potential doubling time and labeling index, as measured by flow cytometry in patients with head and neck squamous cell carcinoma treated with conventional radiotherapy. METHODS AND MATERIALS 70 patients with a squamous cell carcinoma of the oropharynx and 4 patients with another involved head and neck site were entered in this prospective study. The duration of the S phase (TS), the labeling index (LI), and the potential doubling time (Tpot) were obtained by flow cytometry measurements of a tumor biopsy obtained after i.v. injection of 200 mg bromodeoxyuridine to the patient. The treatment consisted of 70 Gy in 7 weeks, 2 Gy per fraction and five fractions per week. RESULTS The mean and median LI were 7.7% (standard deviation, SD: 5.0) and 6.3%, respectively. The mean and median TS were 9.3 h (SD: 3.6) and 8.3 h, respectively. The mean and median Tpot were 5.6 days (SD: 5.4) and 4.6 days, respectively. No significant relationship was found between the Tpot or LI and the tumor stage (T), nodal status (N), histological grade, and the site of the primary within the oropharynx. The only parameter significantly associated with an increased risk of local relapse was the tumor stage (p < 0.001). The mean Tpot for the group of tumors that relapsed locally was 5.3 days (SD: 3.3), compared to 6.1 days (SD: 4.08) for those who did not relapse locally (NS). Two parameters were significantly associated with a decrease in disease-free (DFS) and overall survival, namely the tumor stage (p < 0.005, and p < 0.001, respectively, for DFS and overall survival) and nodal involvement (p = 0.02 and (p < 0.005, respectively, for DFS and overall survival). The TS, LI, DNA index, and Tpot were not significantly associated with local relapse, DFS, and survival, either in the univariate or in the multivariate analysis. CONCLUSIONS The method used to evaluate tumor cell kinetics did not provide clinically relevant kinetic parameters for this type of cancer. The classic prognostic factors (tumor stage and nodal status) were strongly associated with clinical outcome.

T1-T2 NO oropharyngeal cancers treated with surgery alone. A GETTEC study.

The aim of this study is to show that surgical treatment of early-stage squamous cell carcinomas of the oropharynx gives identical, if not better, oncological results than the classic radiotherapy treatment in terms of locoregional control and survival. Fifty-three patients (32 T1, 21 T2, all N0) were operated on during the years 1995–2000. Surgical treatment consisted in a resection by the transoral approach in 43 patients (81.13%); ten patients (18.87%) benefited from a pharyngectomy with (seven) or without (three) mandibular resection. A level I to V selective neck dissection was performed on 35 patients, and 5 patients underwent a level II to V selective neck dissection. The 1-, 3- and 5-year overall survival rates were 100, 94.6 and 73%, respectively. There was no significant difference concerning the tumor stage (P=0.69), the initial localization (P=0.64), the macroscopic aspect (P=0.65) and the management undertaken in the different centers (P=0.19). The 5-year rate of specific survival was 100%. The 1-, 3- and 5-year locoregional control rates were 96.22, 92.45 and 88.68, respectively. The oncological occurrences observed were 2 persistent diseases, 5 local recurrences, 11 second primary cancers and 0 nodal recurrences. Seven local failures were observed, all of which were controlled after a second treatment. Eleven patients presented second primary cancers; three died, two are alive with an extension of this second localization, and six are alive and free of disease. The locoregional control provided by surgery alone on T1-T2 N0 oropharyngeal cancers is as good as radiotherapy. Moreover surgery alone makes it possible to spare patients the complications and aftereffects of radiotherapy. It also makes it possible during the recurrences to operate on patients in non-irradiated areas with lower morbidity and mortality. It is all the more beneficial since it will be possible to resort to radiotherapy after surgery if need be.

Botulinum toxin for radiation-induced facial pain and trismus

Objective To report the efficacy of botulinum toxin A for radiation-induced pain, trismus, and masticator spasm in head and neck cancer. Patients and Methods This prospective nonrandomized study included patients in complete remission with radiation-induced pain and trismus with or without masticator spasms. Fifty units of Botox (Allergan) or 250 units of Dysport (Ipsen) were injected transcutaneously into the masseter muscles. Jaw opening was measured and patients answered 20 questions about jaw opening, pain, and cramps, before injection at 1 month. Results Nineteen patients (7 women, 12 men) were included. Median time after radiation therapy was 5 years (range, 11 months to 22 years). At 1 month, no significant increase in jaw opening was recorded. Improvement was noted in the functional domain (P = 0.004), for pain (P = 0.002) and cramps (P = 0.004), but not in the social (P = 0.83) or emotional (P = 0.43) domains. No side effects occurred. Conclusions Botulinum toxin did not improve trismus but significantly improved pain scores and masticator spasms (oromandibular dystonia).

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

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.

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 (pre-epiglottic 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.

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.