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.

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.

[Conservative treatment of tumors of the retina at the Curie Institute. 5-year ophthalmologic results of 129 cases treated with the Stallard disc and electrons]. / Traitement conservateur des tumeurs de la rétine à l'Institut Curie. Résultats ophtalmologiques à 5 ans de 129 cas traités par disque de Stallard et électrons.

The authors report a retrospective study of 129 children with retino-blastoma treated from 1963 to 1977 at the Institute Curie by enucleation of the worst eye and conservative irradiation of the other eye; this irradiation was performed either with Stallard plaque (19 cases) or with electrons (110 cases). In 8 familial cases no enucleation was performed. T.E.M. was used from 1964 to 1973 and iterative photocoagulation has been performed since 1968. Five years absolute NED survival rate was 68% (88/129 children). In these 88 children, 94 eyes were irradiated. Ophthalmological results were as follows: 21 eyes were enucleate secondarily (20/21 were tumoral); the attempt of ocular conservation was succeeded in 78% of the cases: 73 of the 94 irradiated eyes were cured; among these 73 cured eyes, 4 had complications and 15 had sequelae; the others 54 eyes were normal; only 5 eyes escaped ophthalmological survey; for the other 68 eyes vision was evaluated: 2 eyes (3%) were functional but vision could not be measured; 10 (14%) had less than 1/10 of visual acuity; 14 (19%) had vision at least equal to 1/10 but less than 5/10; 42 (57%) had 5/10 or more. 62% of all irradiated eyes (58/94) and 79% of conservated eyes (58/73) had "useful vision". Results are discussed and compared with these published by other teams; the authors try to determine elements of visual prognosis.

[Conservative treatment of tumors of the retina at the Curie Institute. Long-term results of 129 cases treated with Stallard's disk and electrons]. / Traitement conservateur des tumeurs de la rétine à l'Institut Curie. Résultats à long terme de 129 cas traités par disque de Stallard et électrons.

The authors report a retrospective study of 129 children with retinoblastoma treated from 1963 to 1977 at the Institut Curie by enucleation of the worst eye and conservative irradiation of the other eye; this irradiation was performed either with Stallard plaque (19 cases) or with electrons (110 cases). In 8 familial cases, no enucleation has been performed. T.E.M. was used from 1964 to 1973 and iterative photocoagulation since 1968. With a 5 years follow up, 88 children (68%) are living NED, 6 are lost. There was 34 treatment failures (26%) and 1 death from second malignant tumor. At 10 and 15 years, the results are stable despite the occurrence of two other second primary tumors. Irradiation preserved 73/94 (78%) of the irradiated eyes. The technical aspects of the radiotherapy with electrons and both ocular and vital prognostic factors are discussed.

[Role of neoadjuvant chemotherapy in the treatment of advanced head and neck tumors. Results of two randomized therapeutical trials conducted at the Institut Curie on 208 patients]. / Place de la chimiothérapie néoadjuvante dans le traitement des tumeurs avancées de la tête et du cou. Résultats de deux essais thérapeutiques randomisés effectués à l'Institut Curie sur 208 patients.

From March 1983 to December 1989, 208 patients with locally advanced squamous cell carcinoma of the head and neck were successively included into two trials randomizing induction chemotherapy versus no pre-irradiation treatment. The chemotherapy regimen of the first trial, which included 100 patients, consisted of two cycles of a combination of cisplatin, bleomycin, vindesine, mitomycin C; while that of the second trial, which included 108 patients, consisted of three cycles of a combination cisplatin, 5-fluorouracil (continuous infusion) and vindesine. Local treatment was the same in two trials: 'primary' radiotherapy in all patients. The response was then evaluated at 55 Gy; in the case of poor response, 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 and in the first one: 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. Complete response rate at the end of irradiation correlates 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 did not significantly differ in the two groups of patients, with or without chemotherapy. The incidence of distant metastasis was significantly reduced (P < 0.03) in the chemotherapy arms. This negative trial encourages the design of new chemotherapy protocols according to new schemes of treatment. For advanced stages of head and neck cancers (T3, T4, N2, N3), we recently launched a pilot study combining platinum and irradiation, but according to a concomitant schedule.