Jacques Brugère

Differential effects of tobacco and alcohol in cancer of the larynx, pharynx, and mouth

Two thousand five hundred forty male patients with cancer of larynx, pharynx, and mouth were examined in the same hospital between 1975 and 1982. Different sites were compared according to alcohol and tobacco consumption: oropharynx, hypopharynx, larynx supraglottis, larynxglottis, epilarynx, lip, tonguetip, and tongue lateral border, other tongue sites, gum, floor of the mouth, and buccal mucosa. For tobacco, the mean daily consumption of smokers and exsmokers did not differ according to location (except in patients with cancer of the lip, in whom the consumption was lowest). Cancer locations differed significantly according to the daily alcohol consumption. The consumption was the lowest for patients with cancer of the lips and the glottis, the highest for patients with cancer of the epilarynx, hypopharynx, and the floor of the mouth. Significant differences were observed in the percentage of nonsmokers or nondrinkers, even between adjacent locations: supraglottis versus glottis; tongue, tip, and lateral border versus tongue, other sites; floor of the mouth versus buccal mucosa. Some of the results might be particular to elements of the French life‐style (e.g., consumption of brown tobacco, high consumption of wine).

Results of radical radiotherapeutic treatment of carcinoma of the pyriform sinus: Experience of the Institut Curie

Abstract Four hundred and thirty-four consecutive male patients received radical megavoltage radiotherapy for a squamous cell carcinoma of the pyriform sinus between 1958 and 1974. Those who had lateral epilaryngeal cancers were excluded since these tumors have a better prognosis. Cytological examination confirmed that 79 % of patients had T3 disease and 72 % had clinically involved metastatic nodes. The overall absolute and determinate survival at three years was 26% and 47%, and at five years 19% and 41%, respectively. The fact that the determinate survival is significantly better than the absolute survival is an indication that a sizable number of patients died of causes other than their primary tumor. Over half developed locoregional failure and could not be salvaged by surgery. Local control for patients with early stage cancer (T1−T2) who received less than 6500 rad was only 36 % ; it was 65 % for those who received higher doses. There was no significant improvement with increasing doses for advanced disease (T3). Nodal control was improved with increasing radiation doses for nodes ≤ 3 cm as well as for nodes > 3 cm. The incidence of fatal radiation complication was 2.5%. Pyriform sinus cancer is the most lethal tumor of the head and neck region. The majority of patients will present with advanced primary tumors and/or with massive neck metastasis. The results achieved in advanced stages (T3, N2, N3) are universally poor, regardless of the treatment modality used. Patients with early stages should have an improved local control if adequate radiotherapy is administered. Prevention and early diagnosis, at present, appear to be the only hope in improving the dismal survival.

Treatment of metastatic neck nodes secondary to an occult epidermoid carcinoma of the head and neck

One hundred thirty‐eight patients, who were followed for a minimum of 5 years, had either surgery and postoperative radiotherapy (48 patients) or radiotherapy only (90 patients) for metastatic epidermoid carcinoma in cervical nodes from an unknown head and neck primary. All received radiotherapy to the presumed occult sites. Forty‐five percent presented with a single unilateral adenopathy. Those who were initially operable had a neck recurrence rate of 17% and a survival rate of 53%. Forty‐three percent of initially inoperable patients recurred and only 25% survived. Patients with adenopathy which completely regressed or became resectable after irradiation had an 80% locoregional control. Only 4% developed an overt cancer at an occult site within 5 years.

Induction chemotherapy in advanced head and neck tumors : results of two randomized trials

From March 1983 to December 1989, 208 patients with locally advanced squamous cell carcinoma of the head and neck were successively included into two randomized induction chemotherapy trials. The chemotherapy regimen of the first trial, which included 100 patients, consisted of two cycles of a combination of cisplatin, bleomycin, vindesine and mitomycin C; while that of the second trial, which included 108 patients, consisted of three cycles of a combination cisplatin, 5-fluorouracil by continuous infusion and vindesine. Local treatment was the same in the two trials: primary radiotherapy in all patients. The response was then evaluated; in the case of a poor response at 55 Grays surgery was performed; otherwise, radiotherapy was continued to full doses (possibly followed by salvage surgery). The tumor and lymph node responses to chemotherapy (complete and partial response) were higher in the second trial than in the first: 70% versus 50% for primary lesions, 47% versus 25% for lymph nodes. The toxicity of the two chemotherapy regimens was minimal. In the two trials, an initial major response to chemotherapy predicted subsequent efficacy of irradiation in 80% of the patients. The significance of the complete response at the end of the irradiation varies with the previous response to the chemotherapy. With a median follow-up of 60 months with the first chemotherapy regimen and 30 months with the second, overall survival and disease-free interval were very similar in the two groups. The incidence of distant metastasis was significantly reduced (p less than 0.03) with chemotherapy. This trial suggests the need to test new chemotherapy protocols according to new schemes of treatment, with chemotherapy given concurrently with or following the completion of standard treatment by means of multicenter randomized trials.

Results of radiation therapy in carcinoma of the base of the tongue. The curie institute experience with about 166 cases

Between 1960 and 1980, 166 patients with squamous cell carcinoma of the base of the tongue were treated with primary irradiation at the Curie Institute (Paris, France). Distribution according to the TNM system 1978 International Union Against Cancer (UICC) was the following: 22 T1 lesions, 47 T2 lesions, 64 T3 lesions, and 33 T4 lesions. Regional nodes were not palpable in 50 cases, 35 had N1 nodes, 12 had N2 nodes, and 69 had N3 nodes. All patients received external beam radiation. The 2‐year, 3‐year, and 5‐year overall survival rates for all patients were, respectively, 45%, 37%, and 27%. Local control was significantly related to the initial status of the primary, to the tumor regression at the end of the radiation therapy, and to the histologic differentiation. The 2‐year local control was 96% for T1 lesions, 57% for T2 lesions, 45% for T3 lesions, and 23% for T4 lesions. Local control was 70% if the tumor regression was complete at the end of the treatment and 27% if the tumor regression was partial. No significant differences were found in primary local control with respect to degree of infiltration, age, and dose of radiation therapy over a dose of 60 Gy in 6 weeks. The 3‐year regional control was 86% for N0, 78% for N1, and 60% for N2 and N3. Among the tumor characteristics analyzed, the most useful ones for predicting local control and survival were clinical tumor staging parameters and tumor radiation‐induced regression. A new therapeutic approach based on the evaluation of the tumor regression at 50/55 Gy is under discussion.

PROGNOSTIC VALUE OF TUMOR REGRESSION DURING RADIOTHERAPY FOR HEAD AND NECK CANCER: A PROSPECTIVE STUDY

OBJECTIVE Prospective evaluation of tumor regression during external irradiation for head and neck squamous cell carcinomas and its association with long-term local control. METHODS AND MATERIALS Two hundred twenty-eight patients with histologically confirmed squamous cell carcinoma [oral cavity: 59 (26%), oropharynx: 65 (29%), hypopharynx: 37 (16%), larynx: 67 (29%)] were included between January 1986 and December 1990. Curative intent external irradiation delivered 65-70 Gy over a period of 7 weeks (five 2 Gy fractions per week). Tumor regression was evaluated clinically and endoscopically every week. RESULTS Tumor regression, assessed at 2 weeks, was as follows: no response: 62 (30%), 25% response: 121 (59%); 50% response: 23 (11%). At 5 weeks, 9 (4%) patients showed 0-25% regression, 75 (33%) showed 50% regression, 115 (50%) showed 75% regression, and 29 (13%) showed complete regression. Median follow-up was 79 months (range: 6-96 months). The local control probability was 68% (62-74%) at 2 years, 65% (59-70%) at 5 years. Univariate analysis showed that, at 2 weeks, local control was significantly different between the nonresponders and the patients with 25% or greater response (p < 0.025) and that, at the fifth week, local control was very different between the major responders (75 and 100%) and the minor responders (0-50%) (p < 0.0001). Multivariate analysis (Cox Proportional Hazards Model) showed that the probability of local relapse was significantly and independently increased for minor regression at 5 weeks [Relative risk (RR) of failure was 2.3 (1.4-3.7)], for nonlaryngeal tumors [RR: 2.4 (1.3-4.5)], and for Stage T3-T4 [RR:2.4 (1.4-4)]. Three prognostic groups can, therefore, be proposed: 1) low risk of recurrence when regression > or = 75% and laryngeal tumor or T1-T2 tumors in other sites: 106 (46.5%) patients, 2-year local control probability: 84% (77-92%); 2) high risk of recurrence: regression < or = 50% and T3-T4 nonlaryngeal tumors: 44 (19%) patients, 2-year local control probability: 27% (13-41%); 3) intermediate risk of recurrence: 78 (34.5%) patients, 2-year local control probability: 69% (58-80%). CONCLUSION The present study suggests that tumor regression during external radiotherapy is an independent predictive factor of local control in head and neck carcinomas.

Laryngeal and hypopharyngeal cancer and occupation: results of a case control-study.

OBJECTIONS: To ascertain whether certain occupations are associated with laryngeal or hypopharyngeal cancer. METHODS: A hospital based case-control study was carried out in 15 hospitals in France. It included 528 male cases diagnosed between January 1989 and April 1991, and 305 male controls with various other types of cancer. Interviews were carried out to obtain lifetime job histories and information on potential confounders. Logistic regression was used to compute the odds ratios (OR) for each of about 80 occupations and industries. RESULTS: There was an excess risk of laryngeal and hypopharyngeal cancer among service workers (OR 2.2, 95% confidence interval (95% CI) 1.3 to 3.9), agricultural and animal husbandry workers (OR 1.6, 95% CI 0.9 to 2.8), miners and quarrymen (OR 2.0, 95% CI 0.9 to 4.3), plumbers and pipe fitters (OR 2.6, 95% CI 0.8 to 8.1), glass formers and potters (OR 4.3, 95% CI 1.0 to 18) transport equipment operators (OR 1.5, 95% CI 1.0 to 2.5), and unskilled workers (OR 1.7, 95% CI 1.0 to 2.9). Analysis by industrial branch showed an excess risk for coal mining (OR 2.1, 95% CI 1.1 to 4.1), manufacture of metal products (OR 1.9, 95% CI 1.0 to 3.3), and administration and sanitary services (OR 1.7, 95% CI 1.1 to 2.5). CONCLUSION: These results suggest that occupational exposure might have a role in generating laryngeal and hypopharyngeal cancer, and indicate the need for further evaluation of these findings, an for the identification of the carcinogens which might account for the excess risks found for certain occupations.

A study of the interaction of alcohol drinking and tobacco smoking among French cases of laryngeal cancer.

Laryngeal cancer represents an important cause of cancer in France, and the individual effects of alcohol and tobacco on this cancer site are well known. However the problem of the interaction between these agents is less extensively documented, and the role of the high consumptions of alcohol has not been studied frequently. A case-control analysis was undertaken to investigate the joint effect of alcohol and tobacco by comparing 197 glottic and 214 supraglottic cancer cases to 4135 controls representative of the French general population. Heavy drinkers were available from the two groups of cases, the highest alcohol category being equivalent to a consumption of more than 2 litres of wine per day. The relative risks estimated for heavy drinkers and smokers were high, and the results indicated an even stronger effect of alcohol drinking and tobacco smoking on the upper part of the laryngeal region. Additive and multiplicative models were fitted to the data. The multiplicative hypothesis was found to be the most appropriate, implying that the risks associated with alcohol and tobacco multiply when the exposures occur simultaneously. The public health implications of this result and the contribution of heavy drinkers and smokers to the frequency of upper respiratory and digestive tract cancers are discussed.

Laryngeal and hypopharyngeal cancers and occupational exposure to formaldehyde and various dusts: a case-control study in France

OBJECTIVES A case-control study was conducted in France to assess possible associations between occupational exposures and squamous cell carcinomas of the larynx and hypopharynx. METHODS The study was restricted to men, and included 201 hypopharyngeal cancers, 296 laryngeal cancers, and 296 controls (patients with other tumour sites). Detailed information on smoking, alcohol consumption, and lifetime occupational history was collected. Occupational exposure to seven substances (formaldehyde, leather dust, wood dust, flour dust, coal dust, silica dust, and textile dust) was assessed with a job exposure matrix. Exposure variables used in the analysis were probability, duration, and cumulative level of exposure. Odds ratios (ORs) with their 95% confidence intervals (95% CIs) were estimated by unconditional logistic regression, and were adjusted for major confounding factors (age, smoking, alcohol, and when relevant other occupational exposures). RESULTS Hypopharyngeal cancer was found to be associated with exposure to coal dust (OR 2.31, 95% CI 1.21 to 4.40), with a significant rise in risk with probability (p<0.005 for trend) and level (p<0.007 for trend) of exposure. Exposure to coal dust was also associated with an increased risk of laryngeal cancer (OR 1.67, 95% CI 0.92 to 3.02), but no dose-response pattern was found. A significant relation, limited to hypopharyngeal cancer, was found with the probability of exposure to formaldehyde (p<0.005 for trend), with a fourfold risk for the highest category (OR 3.78 , 95% CI 1.50 to 9.49). When subjects exposed to formaldehyde with a low probability were excluded, the risk also increased with duration (p<0.04) and cumulative level of exposure (p<0.14). No significant association was found for any other substance. CONCLUSION These results indicate that exposure to formaldehyde and coal dust may increase the risk of hypopharyngeal cancer.

Alcohol and tobacco consumption in cancer of the mouth, pharynx, and larynx: a study of 316 female patients.

Three hundred sixteen female patients with cancer of the larynx, pharynx, and mouth were examined and the following cancer sites were compared with respect to alcohol and tobacco consumption: oropharynx, hypopharynx, larynx, epilarynx, lip, and mouth. The mean daily tobacco consumption of smokers and ex‐smokers was not significantly different between cancer locations; however, significant differences between cancer sites were observed with regard to the proportion of nonsmokers. The percentage of nonsmokers was the highest for cancer of the lips and the lowest for cancer of the epilarynx. Cancer locations differed significantly depending on daily alcohol consumption. Consumption was the lowest for patients with cancer of the lips. The percentage of nondrinkers was high for cancers of the lips and larynx and low for cancer of the epilarynx. Examination of the nonsmoking/nondrinking females (27.2%) did not reveal any features specific to this group, except that the patients were older.