Daniel Point

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.

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.

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.

Metallothionein expression in mobile tongue squamous cell carcinoma: associations with clinicopathological parameters and patient survival

Theocharis S, Klijanienko J, Giaginis C, Rodriguez J, Jouffroy T, Girod A, Point D, Tsourouflis G & Sastre‐Garau X
(2011) Histopathology59, 514–525

Soluble interleukin-2 receptor serum level as a predictor of locoregional control and survival for patients with head and neck carcinoma

The diagnosis and follow‐up of head and neck carcinoma patients are based exclusively on clinical staging, which cannot always predict clinical outcome accurately. Because oral squamous cell carcinomas produce interleukin (IL)‐6 and tumor necrosis factor (TNF)‐α and express IL‐2 receptors, the authors assessed the prognostic value of the serum levels of these markers.

Women and Squamous Cell Carcinomas of the Oral Cavity and Oropharynx: Is There Something New?

PURPOSE Incidence of squamous cell carcinoma (SCC) of the oral cavity and oropharynx is increasing in French female patients. The objective of this study was to study the clinical and demographic characteristics and the prognosis of this female population. Secondary outcomes were to determine if a subgroup of patient had a different prognosis. MATERIALS AND METHODS A prospective study from 1989 to 2002 of all female patients presenting SCC of the upper aerodogestive tract was conducted. Data for 171 women were extracted. Clinical and histological features were analyzed using chi(2) and log-rank tests along with the Kaplan Meier method and multivariate analysis using the Cox regression procedure. RESULTS Mean patient age was 62 years. Of the study population, 48.5% used tobacco and 34.5% used alcohol. The relative risk of death for overall and cancer-specific survival increased for patients below the age of 45 or over the age of 70 (95% Cl; 0.3-1.05; P = .0085). Tobacco consumption decreased cancer-specific and overall survival (P = .0008 and .0001, respectively). The other prognostic factors we found were tumor and nodal status, previous or simultaneous cancer, oral cavity primary site. CONCLUSIONS Prognosis of oropharyngeal and oral squamous cell carcinomas is less favorable in females who smoke as well as in younger and older women. With these patients, the oversight must be closer. Smoking, however, should be stopped.

Induction Chemotherapy in Advanced Head and Neck Cancer Preliminary results of a randomized study

From March 1983 to June 1986, 100 patients with locally advanced squamous cell carcinoma of the head and neck were randomized to receive either two courses of chemotherapy prior to local therapy (group A), or local therapy alone (group B). Local treatment consisted of primary radiotherapy in all patients. When a poor response was observed after 55 Gy, surgery was performed. The chemotherapy regimen was a combination of cisplatinum, bleomycin, vindesine, and mitomycin C. The response rate to induction chemotherapy (group A) was 50% for the primary tumor (CR: 10% and PR: 40%). At the end of radiotherapy, the overall tumor response rates in the two groups A and B, were 77% and 79% respectively. Complete disappearance of the primary tumor occurred more often than that of the lymph node metastases. The response rate to induction chemotherapy for lymph node metastases was 27.1% (CR: 9% and PR: 18.1%). An initial major response to chemotherapy predicted subsequent efficacy of irradiation on 90% of the cases, while a failure of chemotherapy had no predictive value in this respect. The survival rates in groups A and B were 66.5% vs. 65.1% at 1 year and 35% vs. 46.2% at 2 years. Local disease-free and disease-free intervals were similar in both groups. A Coxs multi-step regression analysis revealed two significant independant prognostic factors: size of primary tumor and nodal status. After adjustment for these factors, the chemotherapy did not seem to improve the effectiveness of the local treatment in terms of loco-regional control and survival.

Prognostic significance of tumor shape and stromal chronic inflammatory infiltration in squamous cell carcinomas of the oral tongue

BACKGROUND Squamous cell carcinoma (SCC) of the oral tongue is well known to be an aggressive disease with early metastatic spread in early stage tumors. It is also established that locoregional recurrences are the main causes of treatment failure. Thus, the identification of histopathological factors possessing a predictive value remains important for the management of the disease. The aim of the present study was to define histopathological parameters of the tumor and to compare with the follow-up and status in primary SCCs of the mobile tongue. METHODS Histopathological parameters such as mitotic index, the presence of vascular emboli or perineural invasion, the thickness of the tumor, the histological grade, the tumor shape as well as chronic stromal inflammatory infiltration were assessed in 52 patients with SCC of the mobile tongue and compared with the follow-up and status in patients treated initially by surgery. RESULTS Tumor shape was significantly associated with the presence of perineural invasion. Well-defined shaped tumors displayed almost half the incidence of perineural invasion when compared with ill-defined shaped tumors. In addition, the high density of the chronic inflammatory infiltration of the stroma exhibited significant correlation with the survival of the patients. Finally, the intense chronic inflammatory infiltration of the stroma was associated with well-defined shaped tumors. CONCLUSION Tumor shape and stromal chronic inflammatory infiltration should be considered in the planning of the management of patients with SCC of the mobile tongue.