J. M. Richard

Multiple synchronous and metachronous cancers of the upper aerodigestive tract: A nine‐year study

Three hundred fifty (42.1%) of these multiple cancers were considered synchronous, while 480 (57.9%) were classified as metachronous.

Prognostic factors in cervical lymph node metastasis in upper respiratory and digestive tract carcinomas: study of 1,713 cases during a 15-year period.

A prospective study of 1,713 patients with squamous cell carcinoma of the head and neck submitted to neck dissection between 1957 and 1973 is presented.

Pharmacokinetics of intra-arterial and intravenous cisplatin in head and neck cancer patients

After administration of cisplatin (50 mg/m2 on days 1 and 2) by intra-arterial or intravenous infusions over 1 or 6 hr to a total of 24 patients with head and neck cancer, the main pharmacokinetic parameters of platinum were determined according to a multicompartmental analysis. Elimination half-life of total platinum is greater than 3 days, the amount of platinum recovered in the urine over 7 days accounting for 15-50% of the administered dose. The half-life of filterable platinum species was calculated from the urinary excretion data: 39 +/- 17 min (i.a./1 hr), 37 +/- 24 min (i.a./6 hr), 58 +/- 17 min (i.v./1 hr) and 51 +/- 22 min (i.v./6 hr). Biopsies of the tumor were also analyzed on day 3 for their platinum content. The mean concentrations of platinum in biopsies were: 2.72 micrograms/g (i.a./1 hr), 3.89 micrograms/g (i.a./6 hr), 1.27 micrograms/g (i.v./1 hr) and 1.38 micrograms/g (i.v./6 hr). Tumor regression, based upon clinical and histological data, was only moderate after this single chemotherapy course.

Randomised EORTC Head and Neck Cooperative Group trial of preoperative intra-arterial chemotherapy in oral cavity and oropharynx carcinoma

Between February 1978 and January 1984, 222 eligible patients were randomised in a multicentre trial of preoperative intra-arterial chemotherapy in the treatment of oral cavity and oropharynx carcinoma. Patients were randomised between either surgery or preoperative chemotherapy. This latter group received vincristine and bleomycin for 12 days. Patients were stratified according to the primary site: floor of the mouth (FM) versus posterior oral cavity or oropharynx (POC) and institution. The FM group received postoperative radiotherapy depending upon quality of the margins and lymph-node pathological involvement, when it was systematically applied in the POC group. Tumour regression after chemotherapy either complete (CR) or partial (PR greater than 50%) was observed in 48% in the FM group and 41% in the POC group, and lymph-node regression (CR + PR) was respectively 15% and 23%. Some discrepancies appeared between clinical regression and pathological response, and the number of cases without histological response was clearly higher than the number of cases without clinical response. The overall survival showed a statistically significant difference (P = 0.048) between FM and POC groups. In the FM group, median survival in the chemotherapy arm was estimated at 7 years compared with 3 years in the surgery arm. In the POC group, median survival was estimated at 3 years in both treatment arms. Chemotherapy lowered the uncontrolled disease and local recurrence in the FM group. These differences do not exist in the POC group, which may be due to the systematically postoperative radiotherapy.

Recurrent and/or metastatic head and neck squamous cell carcinoma: A clinical, univariate and multivariate analysis of response and survival with cisplatin-based chemotherapy†

One hundred two patients with recurrent and/or metastatic head and neck squamous cell cancer were entered into four consecutive phase II trials, all cis‐platinum (C‐DDP, 100 mg/m2/cycle)‐based. The two combinations tried were C‐DDP, bleomycin, and fluo‐rouracil (CFB) on 54 patients, and cisplatinum and vindesin in 36 patients (CV). The CFB combination was given with C‐DDP by continuous infusion over 96 hours (23 patients) or on day 1 (31 patients). The CV regimen was also given in two different schedules, with VDS at 3 mg/m2/g weekly (12 patients) or by a 96‐hour continuous infusion (0.6 to 1.0 mg/m2/d) in 24 patients. The following variables: sex, age, performance status, previous therapy, local recurrence, length of disease‐free interval (DFI), distant metasta‐ses, weight loss, primary site, histological differentiation, type of chemotherapy, previous chemotherapy, evaluable/measurable disease, erythrosedi‐mentation rate, and their relation with response to chemotherapy (WHO) and survival were submitted to both univariate and multivariate analysis (Cox). Overall response rate (RR:CR+PR) was 25 (28%) of 90. In the CFB protocols, RR was 12 (22%) of 54 us. 13 (38%) of 36 (P = 0.15, NS) in the CV combination group. For the four different combinations the RR was CFB C‐DDPci 7 (30%) of 23, CFB C‐DDP 1 hour 5 (16%) of 31, CV VDS weekly 2 (17%) of 12, CV VDSci 11 (45%) of 24. The patient populations were very different, with the latest combination consisting of metastatic patients exclusively. Univariate analysis of multiple variables showed age <60 years, PS:0 or 1, no previous therapy, absence of local relapse, metastatic disease, long DFI, and that measurable disease was significant for the probability of response. Median survival was 7 months for the 90 evaluated patients, 5 months for nonresponders, and 9 months for responders (P = 0.01). In the univariate analysis, significant factors for survival were PS:0 or 1, a weight loss below 10%, long DFI, response to chemotherapy, erythro‐sedimentation rate (ESR) of <30 mm/lst hr, presence of bone metastasis, and the number of metastases. Multivariate analysis shows PS, the absence of local relapse, and disease‐free interval as significant prognostic factors for response. Multivariate analysis factors of significance for survival were PS, weight loss, and response to chemotherapy. The analysis of the clinical pattern showed an evolution in RR from 3 (8%) of 36 on previously irradiated local recurrent disease to 8 (73%) of 11 in previously untreated patients with metastatic disease at presentation.

Olfactory esthesioneuroma: A report of 40 cases

Olfactory esthesioneuroma is a rare malignant tumor arising in the olfactory epithelium. Forty cases observed at the Institut Gustave‐Roussy from 1956 to 1987 are reported. This tumor usually grows slowly and is usually local, but it is important to be aware of the possibility of lymph node involvement (17%) and, particularly, of rapid development of distant metastases (25%), usually within 6 months. CT scan, and more recently, NMR have proved to be of value in choosing the surgical approach. In view of the usual point of departure, a combined neurosurgical and transfacial approach seems to be a satisfactory approach for obtaining oncological control of the lesion. The role of chemotherapy is discussed. The main prognostic factors seem to be the size of the lesion, the intracranial extension, and the lymph node involvement.

Neoadjuvant chemotherapy consisting of cisplatin and continuous infusions of bleomycin and 5-fluorouracil for advanced head and neck cancer : the need for a new stratification for stage IV (MO) disease

A Phase II study of cisplatin (100 mg/m2 on day 1 and bleomycin (15 mg intravenous push day 1) followed by 5 days of continuous intravenous infusions of 5‐fluorouracil (5‐FU) (650 mg/m2/d) and bleomycin (16 mg/m2/d) repeated at 21‐day intervals was performed in 54 previously untreated patients with nonmetastatic (MO), locoregionally advanced head and neck squamous cell carcinoma (SCC). The aim of this study was to increase the complete response rate to chemotherapy and to identify prognostic factors that may influence local control and disease‐free survival. From April 1986 until August 1988, 5 patients with Stage III and 49 with Stage IV (International Union Against Cancer‐American Joint Committee on Cancer 1986 [UICC‐AJCC]) disease received this regimen. Thirty (61%) patients with Stage IV disease had bulky nodal disease (9 N2c and 21 N3) and 29 (53%) had T4 primary lesions. The response rate was 59% (95% confidence interval, 47% to 71%) and the complete response rate to chemotherapy was 13% (95% confidence interval, 0% to 26%). The response rate was greatly influenced by tumoral volume and performance status (PS). The complete response rate to chemotherapy was 40% for patients with Stage III disease (2 of 5 patients) versus 10% for patients with Stage IV disease (5 of 49 patients; P = 0.02). The response rate for patients with Stage III disease was 100% (5 of 5 patients) versus 55% for patients with Stage IV disease (27 of 49 patients; P = 0.14). For patients with Stage IV bulky nodal disease (N2c‐N3), the response rate was 43% (13 of 30 patients) and the complete response rate to chemotherapy was 3% (1 of 30 patients) versus 68% (13 of 19 patients; P = 0.13) and 21% (4 of 19 patients; P = 0.07), respectively, for patients with Stage IV less than N2b disease. The local control rate after definitive therapy was 100% for patients with Stage III disease, 70% (17 of 24 patients) for patients with Stage IV less than N2b disease, and 17% (5 of 30 patients) for patients with bulky nodal disease (P = 0.0005). As of February 1991, with a median follow‐up time of 38 months (range, 30 to 53 months), 4 of 5 patients with Stage III disease and 7 of 19 patients with Stage IV less than N2b disease were alive with no evidence of disease (37%) versus 0 of 30 patients with bulky nodal disease (P = 0.001). In advanced head and neck SCC, the variations in the complete response rate to chemotherapy, the obtaining of local control, and the success of multimodality treatment depend on tumoral volume, especially nodal tumoral volume. The differences between Stages III and IV, and within the Stage IV category for greater than N2c‐N3 disease, point to the need for a better definition of prognostic groups in future trials. Cancer 68:2109–2119.

Hypopharyngeal sebaceous carcinoma: A case report

A hypopharyngeal squamous-cell carcinoma with sebaceous differentiation is reported. In the primary as well as the metastatic lymph nodes, the tumor showed basaloid, squamous, and sebaceous cells. In addition, immunostaining for S-100 protein and vimentin manifested scattered cells showing cytoplasmic processes suggesting myoepithelial cells. An exhaustive review of the literature revealed only one similar case previously reported. The probable origin from the minor salivary glands is discussed.