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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.

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.

Gene amplifications in the q13 band of chromosome 11 are among the most frequent genetic alterations in head and neck squamous cell carcinomas. Previous studies have suggested that such amplification is a marker of aggressive tumor evolution. Their potential for predicting subclinical lymph node invasion or disease recurrence was investigated in a prospective series of 50 oral and oropharyngeal carcinomas. Cell DNA content was also measured in 32 tumors of this series. Gene amplifications affecting the 11q13 band were detected in 11 of 50 (20%) patients, a relatively low frequency in comparison with data reported previously for other carcinomas of the upper aerodigestive tract, especially hypopharyngeal carcinomas. These gene amplifications were preferentially associated with aneuploidy. Cervical lymph nodes of 26 clinically N0 (Tumor-Node-Metastasis staging) patients were surgically explored. The frequency of 11q13 amplifications was very similar in the presence or in the absence of histological invasion, 3 of 15 (20%) and 2 of 11 (18%), respectively. Thus, 11q13 amplifications do not appear to be a reliable marker for prediction of subclinical lymph-node invasion in oral and oropharyngeal carcinomas. The detection of 11q13 amplifications was also not associated with a higher risk of disease recurrence. These data suggest that not only the prevalence but also the prognostic significance of 11q13 amplifications varies between tumors at different sites in the upper aerodigestive tract.

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.

Because contemporary treatment of oral cavity cancer involves procedures that spare the tongue and mandible, an adequate assessment of the oral cavity is essential for appropriate surgical and radiation therapy planning. Computed tomography (CT) and magnetic resonance (MR) imaging, which allow differentiation between soft tissues, are valuable tools for assessing this complex region. Their main advantage resides in their capacity to show at best the normal anatomy and the exact extent of a low-lying tumor. For display of soft tissues and tumor, MR imaging, being a multiplanar and multicontrast technique, is superior to CT. Nonenhanced T1-weighted MR imaging is better for defining the exact extent of medullary bone invasion, which appears as a low-signal-intensity area within hyperintense medullary fat. CT is optimal in detection of cortical bone invasion, which appears as an interruption or erosion of the peripheral hyperattenuating rim. Thus, in cancer of the tongue, MR imaging should be performed first. If tumor extension to the mandible is suspected (due to clinical or MR imaging findings), CT should be added. In cancer of the floor of the mouth, both MR imaging and CT should be performed in the initial work-up, especially in those cases in which there is a clinical doubt about mandibular extension of disease. The main drawback of both modalities is their lack of specificity; other methods are needed to discriminate between tumors and inflammatory or infectious diseases, particularly in the mandible. However, once the diagnosis has been confirmed histologically, treatment can be chosen based on complementary information obtained from CT and MR imaging.

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.

Among the various procedures of pharyngeal reconstruction after circumferential pharyngolaryngectomy, the free jejunal autograft (FJA) has become a common one. We retrospectively reviewed 73 cases of reconstruction with FJA after resection for advanced hypopharyngeal carcinomas (70 primary reconstructions, 3 secondary reconstructions). Postoperative outcome, functional and carcinologic results were studied. There were 1 postoperative death, medical complications in 19 patients, 4 graft failures (5.5%), 11 salivary fistulas. The nasogastric tube was removed before the 15th day in more than a half of the patients. One year postoperatively all the evaluable patients were able to take an oral diet (solid or soft diet for 97% of them). The postoperative radiotherapy was well tolerated. Cancer developed further in 33 patients (13 local and/or nodal recurrences, 13 isolated metastasis, 7 second primaries). The overall survival rate was 44.8% at three years. It seems clear that FJA allows good functional results and increases the quality of life in such patients with poor prognosis.

Purpose: To report preliminary results of a very accelerated radiation therapy Phase I/II trial in locally advanced head and squamous cell carcinomas (HNSCC)., Methods and Materials: Between 01/92 and 06/93, 35 patients with an unresectable HNSCC were entered in this study. Thirty-two (91%) had Stage IV, and 3 had Stage III disease. The mean nodal diameter, in patients with clinically involved nodes (83%), was 6.3 cm. The median Karnovsky performance status was 70. The treatment consisted of a twice daily schedule (BID) giving 62 Gy in 20 days., Results: In all cases, confluent mucositis was observed, which started about day 15 and resolved within 6 to 10 weeks. Eighty percent of patients had enteral nutritional support. The nasogastric tube or gastrostomy was maintained in these patients for a mean duration of 51.8 days. Eighteen patients (53%) were hospitalized during the course of treatment due to a poor medical status or because they lived far from the center (mean 25 days). Nineteen patients (56%) (some of whom were initially in-patients) were hospitalized posttreatment for toxicity (mean 13 days). Five patients (15%) were never hospitalized. During the follow-up period, 12 local and/or regional failures were observed. The actuarial 18-month loco-regional control rate was 59% (95% confidence interval, 45-73%)., Conclusions: The dramatic shortening of radiation therapy compared to conventional schedules in our series of very advanced HNSCC resulted in: (a) severe acute mucosal toxicity, which was manageable but required intensive nutritional support in all cases; and (b) high loco-regional response rates, strongly suggesting that the time factor is likely to be critical for tumor control in this type of cancer.

Undifferentiated nasopharyngeal carcinoma (UCNT) is known to be radiosensitive and chemosensitive, but the latter has never been studied prospectively with phase II methodology. After an intensive work-up, 49 patients with recurrent (REC) and/or metastatic (MTS) UCNT were treated with three monthly cycles of cisplatin (CDDP) 100 mg/m2 day 1; bleomycin 15 mg intravenously (IV) day 1, and 16 mg/m2/d continuous infusion (CI) days 1 to 5; and fluorouracil (5FU) 650 mg/m2/d CI days 1 to 5 (PBF). Of the 49 patients, 33 were North African. The sex ratio was three males:one female, and the median World Health Organization (WHO) performance status was 1.6. In the 48 patients assessable for response, we observed nine (19%) complete responses (CRs) and 29 (60%) partial responses (PRs) (60%), for a 79% overall response rate (95% confidence interval, 68% to 90%) in the assessable group and a 78% global rate. There were eight CRs (24%) observed in the group without previous chemotherapy (33 patients) compared with one CR in the chemotherapy pretreated group (16 patients). Four patients are still alive without evidence of disease after 52+, 54+, 58+, and 58+ months, respectively. All of them had less than three bone MTS sites, and received radiation therapy in these sites. The results confirm the chemosensitivity of UCNT, and the observation of unmaintained long-term responders makes curability a possible consideration.

The association of squamous cell carcinoma of the upper aerodigestive tract with well-differentiated thyroid carcinomas has rarely been reported in the literature. We report 10 cases illustrating this occurrence. In eight cases, the thyroid carcinoma was discovered accidentally on histological examination of a single neck node, a neck node dissection specimen, an unexpectedly found thyroid nodule, or a systematically resected thyroid lobe, all during surgical treatment of an upper aerodigestive tract carcinoma. In the other two cases, metastatic thyroid neck nodes appeared during the follow-up of a patient with an upper aerodigestive tract carcinoma. No case of upper aerodigestive tract carcinomas was found during the follow-up of thyroid cancer patients. In most cases, adequate thyroid cancer surgery was performed simultaneously or later. Prognosis was essentially determined by the upper aerodigestive tract cancer.

Electrochemotherapy (ECT) is a new antitumor treatment which consists in delivering electric pulses to the tumor some minutes after an intravenous injection of bleomycin. We report here the first clinical trial of ECT, applied to patients with permeation nodules of head and neck squamous carcinomas. ECT was well tolerated by patients, no serious incident occurred and a clear antitumor efficiency was found.

Twenty-eight patients with synchronous esophageal and head and neck epidermoid cancers have been treated by a combined protocol including esophagectomy. Seventy-nine percent received pre-operative chemotherapy, 50% had resection of the head and neck lesion at the same time as the esophagectomy and 79% received post-operative irradiation. Two patients died during the post-operative period (7%), and 1, 2 and 3-yr survival rate (Kaplan-Meier) was respectively 64, 32 and 27%. Contrary to our initial assumption, there was no significant decrease in survival compared to patients operated on for an isolated esophageal cancer. The patients were divided into 4 very simple prognostic groups based on the T and N stages of the clinical pre-therapeutic TNM classification: T1 or T2 for esophageal lesions and different T or N stages according to the prognosis for head and neck lesions. A study of each group tended to show that esophagectomy was beneficial except in cases of synchronous T2 esophageal cancer and locally advanced head and neck cancer (there was 2-yr survival in this group). The 28 patients studied represent a particular population which presented 91 cancerous localisations during the duration of the study (mean: 3.25 localisations per patient).

Undifferentiated carcinoma of nasopharyngeal type (UCNT) is a geographically endemic, Epstein-Barr virus-related carcinoma of epidermoid origin with reported 5-year survival rates of 15%-40% when treated with radiotherapy alone. Although UCNT can be well controlled locally by radiation therapy, in advanced nodal stage N3 [International Union Against Cancer-American Joint Committee on Cancer (UICC-AJCC, 1987)] the survival rate is below 20%, primarily because of metastatic spread in 80% of the fatalities. We report a pilot study of 41 patients with nonmetastatic, locoregionally advanced disease (85% of the patients had a nodal status greater than or equal to N2C-N3; 43% had T4 primaries), during which we used a combination of 100 mg of cisplatin/m2 on day 1, 15 mg of bleomycin by intravenous push and 12 mg/m2 by continuous infusion on days 1-5, and 70 mg of epirubicin/m2 on day 1 every 21 days for three cycles before definitive radiation therapy with 70 Gy for 7 weeks. Twenty-seven of 41 patients (66%; 95% confidence interval = 52.5%-80.5%) achieved a clinical complete response, and 40 of 41 (98%) had a major objective response after chemotherapy. Two deaths were treatment related, but side effects were moderate, and the overall treatment sequence was feasible. At the end of radiation therapy, all 39 assessable patients were in complete response, with a median follow-up of 21+ months (greater than 10-greater than 31); 33 (80%) patients had no evidence of disease. We believe that such a complete response rate in a high-volume disease with the use of combined modality treatment indicates a therapeutic gain in UCNT. Researchers performing a multicenter international controlled trial will test this hypothesis and compare local control, disease-free, and overall survival of the therapeutic sequence presented here with radiotherapy alone.

Delayed hypersensibility to antigens derived from four lymphoid cell lines was measured in 27 non-Chinese patients with nasopharyngeal cancer (NPC) and 63 non-NPC cancer patients. Of the NPC patients, 17/27 (63%) had a positive skin test response to antigens derived from HKLY-28, a lymphoid cell line which was developed from an NPC biopsy. Only 10/51 (20%) and 1/13 (8%) patients with solid tumors and hematopoietic malignancies, respectively, had positive skin test responses to HKLY-28. Positive skin tests were found less frequently when extracts from cell lines derived from normal individuals or lymphoma patients were utilized, although NPC patients were more reactive to two of the non-NPC derived cell lines than the controls. The NPC patients in this study also had significantly elevated antibody titers to the Epstein-Barr virus (EBV), capsid antigen (VCA) and early antigen (EA). Titers were highest in the patients with more anaplastic nasopharyngeal carcinomas. The skin test and serologic data are consistent with studies in Chinese patients, indicating that NPC in non-Chinese and Chinese patients is biologically similar.

Cancer of para-nasal cavities represented only a small group among cancers of upper aero-digestive tract; 3 to 4% of 1,200 admissions yearly with cancer of head and neck. These cancers may arise from bone or cartilage but originated mainly in the mucosal lining of nasal and sinus cavities. In the latter case these were carcinomas representing approximately 75% of nasosinusal cancers treated. Carcinomas are reviewed, with a distinction between epidermoid and glandular types due to their particular evolutive courses, this retrospective study involving 162 case-reports of patients over 16 years of age treated entirely in the Institut Gustave-Roussy between 1965 and 1980.

This study is a retrospective analysis of 216 cases of malignant tumours of the nasal cavity and paranasal sinuses, treated from 1965 to 1980. The mean age at diagnosis was 59 years, 70 per cent were men and 30 per cent women. There were 121 (56%) epidermoid carcinomas, and 31 (14%) adenocarcinomas. Three-year and five-year actuarial survival rate was 40 and 33 per cent respectively for epidermoid carcinomas, 72 and 50 per cent respectively for adenocarcinomas. Recurrences occurred in 46 per cent of epidermoid carcinomas and 42 per cent of adenocarcinomas. Early diagnosis is important to improve the survival rate, and radical primary treatment should be carried out to reduce the rate of recurrence.

Three cases of lymphoepitheliomas of the larynx are reported. This type of carcinoma--which occurs almost exclusively in nasopharynx--is very unfrequent in the larynx (0.2%). In the 3 cases, the tumors arose in a ventricular diverticulum which presented the same lymphoepithelial structure as the tonsils. Under such conditions, these lymphoepitheliomas, which have to be called 'undifferentiated carcinomas of nasopharyngeal type' are believed to develop from the lymphoepithelial tissue of the laryngocele.

Between 1958 and 1973, 131 patients with carcinoma of the posterior pharyngeal wall were treated at the Institute Gustave-Roussy (127 men, 4 women, mean age 61 years). Nine had a tumor of the oropharynx, 37 of the hypopharynx and 85 of the oro-hypopharynx. Nine had T1 tumors, 19 T2 and 103 T3 (TNM-UICC 1975). 122 patients were treated by irradiation: 83% were T3 lesions, 81% were more than 4 cm in diameter, 80% were ulcerated and 42% were staged N3. The survival rate of these patients was very poor (3% at five years). The nine patients who had been treated by surgical excision had a better survival rate and three are alive at 5 years, but the initial prognostic factors were better in this group. It seems that the indications for surgery should be widened to increase the survival rate in these poor prognosis cancers.

A review of 2262 squamous cell carcinomas of the tonsillar region seen at the Institut Gustave-Roussy, Villejuif, France, from 1970 to 1986 showed 1837 well- and poorly differentiated squamous cell carcinomas and 425 undifferentiated squamous cell carcinomas. Eighteen patients with undifferentiated squamous cell carcinomas presented histologic characteristics of undifferentiated carcinomas of nasopharyngeal type. Radiosensibility and radiocurability (complete sterilization with 70 Gy administered) was found in this group with an excellent long-term control of local disease (77% at 10 years actuarial). Epstein-Barr virus-related serologic tests were performed for seven patients. Four of them presented the serologic anti-Epstein-Barr virus titer patterns, generally associated with undifferentiated carcinomas of nasopharyngeal type (1280 to 5120 for viral capsid antigen/IgG and 40 to 320 for viral capsid antigen/IgA). These observations confirm that undifferentiated carcinomas of the nasopharyngeal type may arise outside the nasopharynx.