Françoise Brunin

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.

Primary radiotherapy of squamous cell carcinoma of the oropharynx and pharyngolarynx: Tentative multivariate modelling system to predict the radiocurability of neck nodes

In a series of 1251 cases of squamous cell carcinomas of oropharynx and pharyngolarynx with clinically positive neck and treated primarily by radiation therapy a determinate group of 798 cases remained eligible for a multivariate analysis of the prognostic factors related to the regional outcome. Node size (p less than 0.0001), node fixity (p = 0.016) and T stage (p = 0.02) were the significant pretreatment factors independently predictive of neck node control. when regarding the treatment modalities in this determinate group of patients who received tumor doses of at least 55 Gy, only the treatment duration was found to be predictive (p = 0.002). Based on these factors, a multivariate model was constructed and tested by estimating the product-limit survival of the various groups of patients. The predictive accuracy of the equation was assessed by the log-rank test significance levels. The model may help to select, in many clinical situations, the appropriate approach of the management of metastatic neck disease, either by definitive radiation therapy or by combined modalities.

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.

Serum soluble interleukin–2 receptor concentrations as an independent prognostic marker in head and neck cancer

Currently head and neck squamous cell-carcinomas are staged clinically, though this is not ideal. We did a multivariate prospective study of 234 patients with head and neck squamous-cell carcinoma and showed that high serum concentrations of sIL-2Ralpha at diagnosis were highly correlated with a shorter survival (p<0.0001). In addition, patients who had low serum sIL-2Ralpha concentrations at diagnosis were less likely to develop distant metastasis during the 36 months follow up compared with the group with high serum sIL-2Ralpha concentrations (p<0.001). These findings suggest that serum sIL-2Ralpha could be considered as an independent serum biomarker in head and neck cancer patients.

Impact of neck node radioresponsiveness on the regional control probability in patients with oropharynx and pharyngolarynx cancers managed by definitive radiotherapy.

We reviewed a series of 1,666 patients with squamous cell carcinoma of the oropharynx and pharyngolarynx treated with definitive radiation therapy to determine whether or not radioresponsiveness of the metastatic neck nodes is a reliable indicator of their radiocurability. In a determined group of 708 patients with clinically positive neck nodes, only one third of the adenopathies (247/759) completely regressed at the completion of the treatment. At 6 months, only ten percent of the nodes remained palpable. Lymph node clearance rates and halving diameter times were tumor size-dependent. Node clearance rate was also influenced by the site of the primary lesion. The impact of various parameters, both intrinsic and extrinsic to the tumor behavior, is discussed. Neck control probability was significantly higher for complete responders. In this group, the ultimate node control was as good for adenopathies larger than 6 cm as for the smaller ones. Tumor control probability directly related to clearance rate following radiotherapy. Finally, therapeutic implications are derived for nodal dose adjustments and optimal applicability of radiosurgical combinations.

External radiotherapy for carcinoma of the eyelid: Report of 850 cases treated

PURPOSE We report a retrospective series of 850 patients treated by external irradiation for carcinoma of the eyelid at Institut Curie and we compare our results with other techniques: brachytherapy and surgery. METHODS AND MATERIALS Eight hundred fifty patients were treated by external radiotherapy for carcinoma of the eyelid. None of these patients have been previously treated. All the patients were classified according to the TNM classification of (UICC). We distinguished five histological types and five clinical groups according to the site of the skin tumor. Three modalities of external radiotherapy were used: contact therapy, conventional radiotherapy, and electrontherapy. We reviewed the clinical files of the 850 patients who went regularly at follow-up visits. RESULTS We report the 5-year survival results--alive with no evidence of disease: 72%; alive with progression: 2%; died from tumor progression: 0.5%; died from intercurrent disease: 19.5%; and lost to follow-up: 5%. The 5-year local control rate was 97.5%. We observed 45 failures--lymph node, metastatic, and local--and emphasize this last group by presenting the results of treatment of these local failures. We studied the complications of treatment: 2.3% of corneal complications, 2% of cataracts, and 1.4% of serious ocular complications. CONCLUSIONS Our results concerning local failures and loss of the eye are comparable to those reported for other techniques involving brachytherapy or surgery. Overall, external radiotherapy is a safe and effective treatment, as it ensures a high local control rate and provides perfectly satisfactory functional and esthetic results. It seemed particularly useful to report this series in that few publications are available on this subject that, nevertheless, constitutes a topical issue.

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.

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.

Impact of cervical disease and its definitive radiotherapeutic management on survival: Experience in 2013 patients with squamous cell carcinomas of the oropharynx and pharyngolarynx

Two thousand thirteen patients with squamous cell carcinoma of oropharynx and pharyngolarynx were reviewed with regard to neck disease presentation and disease‐free survival after radical radiotherapy. All patients were staged according to both the AJCC1976 and the UICC1978 classifications. Causes of failure, disease‐free survival, and complication rates were assessed. Sixty percent had a clinically positive neck. The 3‐year disease‐free survival rates were 58%, 44%, 38%, and 25% for AJCC NO, Nl, N2, and N3 cases, respectively. Corresponding UICC figures were 58%, 46%, 26%, and 29%. Analyzed parameters were nodal stage, size, site and fixity, and location of primary. Complications attributed to neck disease did not exceed 3%. A critical appraisal of the nodal staging systems is derived from these sets of data.