D. Chassagne

Elective versus therapeutic radical neck dissection in epidermoid carcinoma of the oral. Cavity results of a randomized clinical trial

This study concerns 75 patients with squamous cell carcinoma of the oral cavity who were patients at the Gustave‐Roussy Institute between December 1966 and July 1973. These patients were divided into two groups. The first group was comprised of 39 patients who underwent elective radical neck dissection; nodal involvement was present in 49% with capsular rupture in 13%. In the second group of 36, neck disease appeared during follow up in 19 cases. Therapeutic radical neck dissection was carried out in 17; the nodes were histologically positive in 15, 9 of which had a capsular rupture. In 2 cases, local or general conditions did not permit operative intervention. In this group, the involvement rate was 47% with a 25% capsular rupture rate. However, the comparison of the survival curves by the log‐rank test did not reveal any differences, even though histologic prognostic factors were taken into account. These findings led to the conclusion that in squamous cell carcinoma of the oral cavity staged T1N0, T2N0, or T3N0 (from AJCs and UICCs clinical staging system), it seems possible, without risk, to delay neck dissection until a node is detectable, although it is reasonable to perform elective neck dissection in those cases in which the patient is unavailable for regular followup.

Overall treatment time in advanced cervical carcinomas : a critical parameter in treatment outcome

PURPOSE To search for possible influence of overall treatment time on the clinical outcome of advanced cervical carcinomas treated with radiation alone. METHODS AND MATERIALS Three hundred and eighty-six patients with Stage IIB and III cervical carcinomas treated with external radiation and intracavitary curietherapy between 1973 and 1983 were entered in the study. A multivariate analysis was carried out on data concerning these patients to determine whether overall treatment time was a prognostic factor. RESULTS Overall treatment time and blood transfusions during treatment were the two most highly significant factors in the multivariate analysis. Loss of local control and overall survival, when treatment exceeded 52 days, was approximately 1% per day in both cases. CONCLUSION These results suggest that overall treatment time might be a highly significant prognostic factor in the treatment outcome of advanced cervical carcinomas. Prospective randomized studies are strongly warranted to confirm this hypothesis.

Prognostic value of hemoglobin concentrations and blood transfusions in advanced carcinoma of the cervix treated by radiation therapy results of a retrospective study of 386 patients

A retrospective study was carried out on 386 patients with advanced cervical carcinomas treated with radiation therapy between 1973 and 1983. The influence of hemoglobin concentrations and blood transfusions before and/or during treatment on the occurrence of distant and/or local regional failures were examined in a univariate and multivariate analyses. In the multivariate analysis hemoglobin concentrations were prognostic only during treatment and patients with at least one value below the threshold of 10 gm% had a significantly higher risk of local regional failure than the patients with all their values above the threshold. Moreover 70% of these high risk patients had less than half of their values below the threshold. It is possible that blood transfusions might be beneficial when given before treatment. However, although it was not significant, blood transfusions given during treatment tended to be an adverse prognostic factor suggesting that blood transfusions might not have completely offset acute anemia prior to transfusion. Our study suggests that anemia during treatment, even of short duration might be detrimental to patients.

Combined radiotherapy and surgery: local control and complications in early carcinoma of the uterine cervix — the Villejuif experience, 1975–1984

From January 1975 to December 1984, 441 patients were treated by combined radiotherapy and surgery at the Institut Gustave Roussy (IGR) for Stage IB (288) and II (proximal) (103) carcinoma of the uterine cervix. Standard treatment consisted of pre-operative utero-vaginal brachytherapy (60 Gy) using a mould technique followed by a colpo-hysterectomy and external iliac lymphadenectomy. Overall 5 year actuarial survival for the whole population was 87% and disease-free survival 85%. Loco-regional relapse occurred in 23 patients (5%). Of these, 12 were central pelvic failures, 8 regional failures and 3 combined central and regional failures. There were 36 systemic relapses (8%) of which 12 relapsed concurrently in the pelvis. Five year actuarial pelvic disease-free, disease-free and overall survival was 87, 85 and 87%, respectively, for the whole population. 340 patients developed one or more complications [Grade 1: 198/441 (44%), Grade 2: 121/441 (27%) and Grade 3 or 4: 21/441 (4.7%)]. Five year actuarial survival for the whole population was poorer for histologically node positive than for node negative (89 vs. 55%, p less than 0.0001). Pre-operative brachytherapy followed by surgery can provide good local control with acceptable morbidity in early cervical cancer.

Twenty years experience of interstitial iridium brachytherapy in the management of soft tissue sarcomas

From February 1968 to February 1988, 50 patients above 10 years of age with a soft tissue sarcoma were treated with interstitial brachytherapy, combined with a wide excision. After pathologic review, 48 were included in the final analysis. A pathological grading was made possible in 41, which showed a majority of high grades (2 + 3 = 86%). Patients presented mainly with small (less than 5 cm: 36) or mid-size lesions (greater than 5 cm: 12). The tumor was located in the limbs (32), trunk (9), and head and neck (7). Four patients had metastases at the time of treatment. Brachytherapy was part of the initial treatment in 22 cases, and of a salvage procedure after previous excision(s) combined or not with another form of treatment in 26. A uniform technique of iridium 192 wires after-loaded in plastic tubing was used. Sixty Gy median doses were delivered with brachytherapy alone (44) or combined with external beam (4). Sixteen patients also received an adjuvant chemotherapy. Follow up ranged from 16 months to 20 years (median 82 months). At the time of analysis, two patients (4%) only had failed in the irradiated volume, but the marginal failures rate (14:31%) was unexpectedly high. Seven of the patients who failed (43%) were salvaged by a second similar procedure. The 5-year survival was 62% in non-previously treated patients and 56.5% in previously treated ones (pNS). By multivariate analysis, only the tumor location appeared predictive of LF (p less than 0.01), which in turn was strongly correlated with the metastatic outcome (p less than 0.01). Necroses were observed in 17 cases (35%) and associated with a benign course in most of them. High dose brachytherapy combined with conservative surgery is highly effective in small and mid-size soft tissue sarcomas located in the extremities and head and neck, whereas in trunk and in recurrent tumors, the adjunction of large fields external radiotherapy and/or possibly polychemotherapy appears necessary.

Results of a european randomized trial of Etanidazole combined with radiotherapy in head and neck carcinomas

Purpose: The aim of the study was to evaluate the efficacy and toxicity of Etanidazole, a hypoxic cell sensitizer, combined with radiotherapy in the treatment of head and neck squamous cell carcinoma. Methods and Materials: A total of 374 patients from 27 European centers were included in this trial between 1987 and 1990. Treatment was either conventional radiotherapy alone (between 66 Gy in 33 fractions and 74 Gy in 37 fractions, 5 fractions per week), or the same radiotherapy dose plus Etanidazole 2 g/m 2 , three times weekly for 17 doses. A minimization procedure, balancing for center, site, and T stage (T1-T3 vs. T4) was used for randomization. Results: Among the 187 patients in the Etanidazole group, 82% received at least 14 doses of the drug. Compliance to the radiotherapy protocol was 92% in the Etanidazole group and 88% in the control group; the main cause of deviation was acute toxicity, which was observed at an equal rate in the two treatment groups. Fifty-two cases of Grade 1 to 3 peripheral neuropathy were observed in the Etanidazole group vs. 5 cases, all of Grade 1, in the control group (p < 0.001). The 2-year actuarial loco-regional control rates were 53% in the Etanidazole group and 53% in the control group (p = 0.93), and the overall 2-year survival rates were 54% in each group (p = 0.99). Conclusion: Adding Etanidazole to conventional radiotherapy did not afford any benefit for patients with head and neck carcinoma. This study failed to confirm the hypothesis of a benefit for patients with N0-N1 disease, which had been suggested by the results of a previous study (10).

External irradiation plus curietherapy boost in 108 base of tongue carcinomas

From 1960 to 1983, 108 patients underwent an association cobaltherapy plus curietherapy boost for a base of tongue carcinoma. This group included 18 T1 tumors, 39 T2, and 51 T3. Cobaltherapy was delivered to a dose of 45 Gy/4.5 weeks to the primary site and the neck. It was completed by an electron boost or a nodal surgery in case of initial nodal disease. Two techniques of Curietherapy were used: plastic tubes and guide-gutters. As most of these implants have been done before 1975, all the doses have been recalculated on the 85% isodose according to the Paris system. They varied from 22 to 88 Gy. The tolerance of the implantation was excellent. Five-year survival of the whole group is 26%. The local control rate is 85% for T1 tumors, 50% for T2, and 69% for T3. Despite the importance of cumulated doses, a few necrosis were observed. Considering the poor outlook of this cancer, its treatment by exclusive radiotherapy requires very high doses which can only be delivered without major sequellae or complication by a combination of cobaltherapy and curietherapy boost.

Interstitial and external radiotherapy in carcinoma of the soft palate and uvula

Forty-three patients, all male, with limited epidermoid carcinoma of the soft palate and uvula were treated by interstitial implant usually associated with external radiotherapy. Most patients received 50 Gy external irradiation to the oropharynx and neck followed by 20-35 Gy by interstitial iridium-192 wires using either guide gutters or a plastic tube technique. Twelve primary tumors and two recurrences after external irradiation alone had implant only for 65-75 Gy. Total actuarial local control is 92% with no local failures in 34 T1 primary tumors. Only one serious complication was seen. Overall actuarial survival was 60% at 3 years and 37% at 5 years but cause-specific survivals were 81% and 64%. The leading cause of death was other aerodigestive cancer, with an actuarial rate of occurrence of 10% per year after treatment of a soft palate cancer. Interstitital brachytherapy alone or combined with external irradiation is safe, effective management for early carcinoma of the soft palate and uvula but second malignancy is a serious problem.

A trial of Ro 03-8799 (pimonidazole) in carcinoma of the uterine cervix: an interim report from the Medical Research Council Working Party on advanced carcinoma of the cervix

A randomised controlled clinical trial of Ro 03-8799 (pimonidazole) was performed in advanced stage II and stage III squamous cell carcinoma of the uterine cervix. A total of 183 patients were contributed by 15 centres in Western Europe and coordinated by the Medical Research Council Trials Office in Cambridge. Analysis has shown poorer local tumour control with a hazard ratio (HR) of 2.1 [95% confidence interval (CI) 1.2 to 3.7] and survival with a HR of 1.6 (95% CI 1.0 to 2.5) in the group given the Ro 03-8799. These results were not materially affected after adjustment of stage or haemoglobin levels in stratified analysis or to inadequate radiotherapy being given to the sensitiser group. A true adverse effect caused by the drug is a possible cause and this might be related to a drug-induced impairment of blood supply to the tumour. When compared with results recorded previously for advanced cervical carcinoma treated by radiotherapy, it was apparent that the tumour control and survival in the sensitiser arm was similar, but the control arm showed results superior to those previously recorded. Whatever is the explantation it can certainly be concluded that the radiosensitising drug, pimonidazole, gave no benefit in the radiotherapy of advanced cervical cancer.

Phase III trial comparing two low dose rates in brachytherapy of cervix carcinoma: Report at two years

This Phase III randomized trial examined the effect of two low dose rates (0.73 or 0.38 Gy.h-1) on the local control, survival, relapse-free survival, complications, and secondary effects in the treatment of cervical cancers. A total of 204 Stage Ib or II cervical carcinoma patients were included between January 1985 and September 1988. Treatment consisted of uterovaginal 137Cs irradiation followed by surgery. The two groups were similar for age, tumor stage and medical or surgical history. Their brachytherapy parameters were also similar (60 Gy pear dimensions, dose to critical organs, total kerma, etc....) There were no differences in the short-term effects or therapeutic outcome. However, overall complications and side effects observed after 6 months were significantly more frequent (p < 0.01) in the higher dose rate group.