A multivariate analysis of prognostic factors in early stage Hodgkin's disease.

A multivariate analysis of the prognostic factors was carried out with a Cox model on 1,139 patients with clinical Stage I + II Hodgkin's disease included in three controlled clinical trials. The following indicators had been prospectively registered: age, sex, systemic symptoms, erythrocyte sedimentation rate (ESR), number and sites of involved lymph node areas, histologic type, clinical stage, pattern of presentation, results of staging laparotomy when performed, as well as the date and type of treatment. A linear logistic analysis showed that most of the indicators are interrelated. This emphasizes the necessity of a multivariate analysis in order to assess the independent influence of each of them. The two main prognostic indicators for relapse-free survival are systemic symptoms and/or ESR and number of involved areas. The only significant factor for survival after relapse is age. Sex has a small but significant influence on relapse-free survival. The relative influence of each indicator varies with the type of treatment and these variations may help in understanding the biologic significance of the indicators.

Local control and survival in soft tissue sarcomas of the limbs, trunk walls and head and neck: a study of 113 cases.

One hundred thirteen patients with soft tissue sarcomas of the limbs, trunk walls, and head and neck have been treated at the Centre François Baclesse since 1972. Of these, 89 histologically confirmed patients were treated with a multimodality treatment protocol. Treatment policy was designed to use each treatment method as efficiently, economically and conservatively as possible: preoperative irradiation at moderate dose to a large volume (6.5 Gy, 2 sessions, 48 hr interval); surgery 48 hr after the last preoperative irradiation; surgical excision was guided and verified intra operatively by the pathologist (with frozen sections); postoperative irradiation aimed at sterilizing all residual isolated and radiosensitive tumor cells, possibly scattered throughout the anatomical region. The total dose is brought to the equivalent of 50 Gy (preoperative dose included). This dose was increased to 60 or even 70 Gy to a restricted volume, when limb conservation was sought, but tumor foci too large for total resection without amputation; actinomycin was added to the first five postoperative irradiations. The results at 5 years were as follows: local recurrence rate, 13.6%; metastatic rate, 28%; survival rate, overall (113 patients,) 65.6%, curative series (89 patients), 75%. When the surgical excision of the primary tumor was histologically complete (54 patients) the local recurrence rate was 1.9%, the metastatic rate 11.6%, and the survival rate 89.6% at 5 years.

Radiation therapy of skin carcinomas: results of a hypofractionated irradiation schedule in 675 cases followed more than 2 years.

Six hundred and seventy-five cases of cutaneous epidermoid carcinomas of the face (excluding the lips, ears and eyelids) were treated with superficial irradiation therapy according to an original dose and time schedule (3 fractions of 1020 R over 14 days), with correction for RBE. The reference dose was always set at the deepest portion of the tumor (100% isodose including the lesion) and surface dose was limited to 125% of the depth dose. The energy used varied according to the thickness of the tumor, and the size of the irradiation fields according to the diameter of the tumor. All other parameters remained constant. The results after a minimum follow-up of 2 years show that the failure rate was low (less than 4%) and could be corrected in 85% of cases. Ninety per cent of recurrences appeared within 3 years; they were central and most frequently observed in nasal locations and basal cell carcinomas. Complications were rare (fewer than 3% of cases), and the majority were cured by medical treatment. Cosmetic results were satisfactory in over 90% of cases. The method used for expression of the dose permits a clear and coherent interpretation of the results: complications and sequelae were closely correlated with the irradiated surface and volume. The hypofractionated irradiation protocol described in this paper offers a simple, ambulatory method for the treatment of cutaneous epidermoid carcinomas of the face which have a particularly high incidence among the elderly. The majority of patients can be treated in this way.(ABSTRACT TRUNCATED AT 250 WORDS)

Radiotherapy as an integrated part of the treatment of soft tissue sarcomas.

A considerable improvement in the prognosis of soft tissue sarcomas in the adult has been obtained with a treatment schedule combining surgery and routine radiation therapy (possibly preoperative and certainly postoperative); local recurrences, the predominant element in the natural history of the disease, have become very rare and limb function is generally maintained. Metastatic risk presents the major problem, and in our series spread of the disease remained uncontrolled in 25% of cases. Further research is required in this area, and a better definition of the risk factors, especially with regard to histology, is needed. We suggest that the possibility of reinforcing treatment of those histological forms at high metastatic risk by the introduction of multidrug therapy after local treatment be investigated. Such studies can only be effectively conducted within the framework of a multicenter collaborative controlled clinical trial.

Combined radiotherapy-chemotherapy for early stages non-Hodgkin's lymphoma: the 1975-1980 EORTC controlled lymphoma trial.

Patients with stage I and II non-Hodgkin's lymphoma (NHL) are considered to have a relatively good prognosis. For this reason, they are seldom referred to specialized centers and the accrual of such patients in controlled studies is limited. Therefore, significant studies of homogeneously treated patients are difficult to collect and the management of these patients remains controversial. Some patients do very well after treatments with minimal toxicity while others require a much more aggressive approach. The Radiotherapy-Chemotherapy Group of the EORTC carried out its second controlled trial on patients with stage I and II NHL from 1975 to 1980. Its first aim was to assess the prognostic value of histologic classifications independently of treatment. The second aim was to compare two therapeutic options within each stage. In stage I, 124 patients were randomized to receive extended field radiotherapy (RT) either with or without adjuvant cyclophosphamide, vincristine prednisone (CVP) chemotherapy (CT). Relapse-free survival (RFS) was higher in patients who received adjuvant CVP but the total survival rates were not different. The RFS was lower in patients with diffuse than in those with follicular architectural histologies; in the former, RFS was not influenced by adjuvant CVP. Those patients who underwent a staging laparotomy had a higher 5-year total survival (TS) independent of the histologic type. Fifty-six stage II patients were included and extended field was randomized versus total nodal irradiation. Subsequently, adjuvant CVP was given to all patients. Results are good in follicular histologies but the advantage for total nodal irradiation is not significant. In diffuse histologies, results were unsatisfactory in both arms; a new therapeutic strategy was designed in which RT and CT are alternated and has been successfully tested in a pilot study.

[Radiotherapy of sarcomas of the soft tissue in the adult]. / Radiothérapie des sarcomes des tissus mous de l'adulte.

Clinical experience has proved henceforth that radiotherapy must be considered as an integral part of the treatment of adult soft tissue sarcomas. When combined with surgery, it considerably reduces the local recurrence rate and increases the long term cure rate to about 70%. Such results can be achieved with the minimal impeding sequellae when the dose of irradiation is adjusted following the quality of the surgical excision. A dose of 50 Gy is sufficient when no microscopic tumoral foci are left in the tumor bed by the surgeon. It must be higher when it is not the case. The residual metastatic risk is about 30%. We begin to know better which factors are linked to this risk. Clinical research is under way to assess the value of adding chemotherapy in the protocol of high risk patients.

[Combined radiotherapy and chemotherapy: pulmonary side effects (author's transl)]. / Effets des associations radiothérapie-chimiothérapie sur le parenchyme pulmonaire.

Systemic chemotherapy and lung irradiation have very similar effects on lung tissue. Several mechanisms are involved, mainly: --cytotoxic effects on lung cells (type II pneumocytes, capillary endothelial cells, and connective tissue); --enhancement of infection; --hypersensitivity and auto-immune phenomena. Acute pneumonitis or chronic lung sclerosis develops which may or may not be compatible with life, depending on the lung volume involved and the clinical course. These effects are dose dependent for radiotherapy, and for most of the chemotherapeutic drugs. In some cases however, the dose-effect relationship is not clear, especially with some drugs such as methotrexate, and sometimes with radiotherapy even when it can be assumed that there is no mistake in dose calculation. It must be stressed that we will lack basic knowledge on the pharmacokinetics and actual concentration of drugs in lung tissue. Additive or supra-additive effects are likely when chemotherapy is combined with lung irradiation, but current relevant data does not allow any firm conclusions to be drawn on the quantitative changes resulting from the association. Prevention of lung complications is however possible if the tolerance doses and the optimal distribution of each agent with time are respected. Combined lung irradiation and bleomycin administration must be avoided.

[Esophageal cancer in Western France. Retrospective analysis of 1400 cases]. / Le cancer de l'oesophage dans l'ouest de la France. Analyse rétrospective d'une population de 1400 cas

A retrospective review was made of 1 400 cases of cancer of the esophagus treated at the Centre "Francois Baclesse" between 1964 and 1975. The disease appeared at an earlier age and more frequently in men (95%) than in women. The lesions were located predominantly in the middle third of the esophagus. There was a high frequency of local, regional and general extension of the disease due to late diagnosis. Less than one-third of the patients were eligible for surgery--which was excluded in the other cases because of age or the presence of associated pathology or secondary neoplasm--and only 10 per 100 of this group were potentially curable.

[Non-Hodgkin's malignant lymphoma. Retrospective study of 64 cases classified according to Kiel's and Rappaport's nomenclature]. / Lymphomes malins non hodgkiniens. Etude rétrospective de 64 cas classés selon les nomenclatures de Kiel et Rappaport.

64 cases of non-Hodgkin malignant lymphomas were the object of a retrospective study: these 64 cases were considered in terms of Kiel's and Rappaport's classifications. The stimultaneous study using the two classifications showed that entities defined in one of them do not correspond to entities defined in the other one. --This study allows us to define: 1) in Kiel's classification, a groupe of lymphomas of favorable prognosis, by opposition with a group of lymphomas of poor progonosis, all stages included; 2) in Rappaport's classification, a group of nodular lymphomas of favorable prognosis, for which the actuarial survival curves, all stages included, seem to accord with the anatomico-clinical data thus far published. Nevertheless, while nodular lymphomas can be identified as lymphomas of favorable prognosis, it does not seem possible to isolate, in Rappaport's classification, a group of lymphomas of poor prognosis by opposition with the favorable prognosis group. This study confirms that, to the morphological entity of the malignant centroblastic centrocytic follicular lymphoma, there corresponds a lymphoma of favorable prognosis whose median is 72 months, all stages included, for an average age of 57.5 years (this median is more than 180 months in the clinically localized stages). This morphological entity of Kiel covers 76 per cent of Rappaport's malignant nodular lymphomas. Nevertheless, 24 per cent of these same malignant nodular lymphomas are considered to be lymphomas of poor prognosis by Kiel and seem to appear as such in our study.

[Multidisciplinary treatment of soft tissue sarcomas: an improvement in prognosis (author's transl)]. / Sarcomes des tissus mous: progrès thérapeutiques par l'application d'un protocole pluridisciplinaire.

The results obtained in the treatment of 45 cases of soft tissue sarcomas are presented. All cases were reviewed and classified according to the modern criteria of malignancy. The treatment schedule comprised: (1) preoperative irradiation: 2 sessions of 6.50 Gy in 48 hours, target volume: whole limb segment; (2) surgical excision 48 hours later with systematic intraoperative histologic verification, until healthy tissue margins are obtained; (3) postoperative irradiation: 3 weeks later delivering a cumulative total dose of 50.00 Gy to the preoperative volume and 60.00 - 70.00 Gy to a reduced volume encompassing the surgical region with protection of vascular axes where possible; (4) chemotherapy: Actinomycin D 0.3 mg/m2 half and hour before the first 5 sessions of postoperative irradiation; (5) bilateral lung irradiation: 4 sessions of 3.75 Gy in 7 days to the whole chest. The results were as follows: local recurrence rate was 9.5 per cent at 5 years. In 21 cases in whom surgical excision was deemed histologically adequate, no recurrences was seen at 3 years (minimum follow-up). Survival at 5 years was 77 per cent. Deaths were due to metastatic spread, especially to the lungs. These results show an improvement as compared with historical series. New progress should be sought in combining a more aggressive type of chemotherapy for cases with high metastatic risk.

[Cancer registry of Calvados, hospital registry of the François- Baclesse Center and mortality statistics: comparisons]. / Registre des cancers du Calvados, Registre hospitalier du Centre Francois-Baclesse et statistique de mortalité: comparaisons.

Incidence rates of the cancer registry of the department of Calvados were compared, by site and by age group, with those obtained from the cancer registry of the comprehensive cancer center in Caen, concerning the population of the department of Calvados. In males, these rates are approximately similar for head and neck sites; for the hospital registry they are 50% of those recorded by the population registry for lung cancer, and 30% for prostatic cancer. In females, the all-sites rates are nearly identical for the youngest age groups and 50% for the older. They are not significantly different for digestive cancer, and 75% for cervix and breast cancer. The incidence rates of both registries were compared with mortality rates. They indicate mortality rates which appear relatively high for the pancreas, and they show imprecisions for the uterus and head and neck (pharynx-larynx) sites.

[Intraoperative abdominopelvic radiotherapy by single dose electrons]. / Radiothérapie abdomino-pelvienne per-opératoire par électrons à dose unique.

Thirty-four patients received, during laparotomy, a 15-20 Gy localized irradiation from a 10-13 MeV beam of electrons supplied by a linear accelerator and focalized by means of a localizer especially designed for this purpose. This technique is indicated for localized residual tumours of the pelvis and intra-operative irradiation of the lumbar aorta, as part of a chemo-radiotherapeutic programme in patients with advanced cancer of the cervix. It is too early to evaluate the medium-term results, but the technique is very well tolerated immediately.

[Radiolesions after radiotherapy of breast cancer]. / Les radiolésions après irradiation pour cancer du sein

A study is presented of the late radiolesions which occur after breast cancer irradiation. These lesions are described and the etiological factors are studied, with special emphasis given to the effect of dose and time factors. For the large volume considered in the irradiation of breast cancers, the tolerance dose for normal tissue (skin and connective subcutaneous tissue) can be set at 1,700 rets, that is, 5,600 rads in 28 sessions of 200 rads over a period of 38 days. Technical irradiation problems are given special mention as they can be the cause of dosimetric errors resulting in complications. Dosimetry should be in the whole volume, and not only in a single plane, as is still most often the case.

[Frequency of complications and radiotherapeutic progresses in Hodgkin's disease (author's transl)]. / Fréquence des complications et progrès radiothérapiques dans la maladie de Hodgkin.

Two categories of iatrogenic effects are observed in Hodgkin's disease: the radiotherapeutic loco-regional complications; the systemic effects in which the long term carcinogenic risk is particularly important to consider. The first category can be avoided by the technical improvements which are steadily achieved. The second category can be minimized with a good therapeutic strategy in which the magnitude and intensity of the treatment are matched to the severity of each anatomical and clinical presentation.

[Bilateral lung irradiation as adjuvant therapy in osteogenic sarcoma ]. / Place de l'irradiation pulmonaire bilatérale dans le traitement adjuvant des sarcomes ostéogènes.

Bilateral lung irradiation as well as chemotherapy are still controversial in the "prevention" of pulmonary metastases from osteosarcomas. This paper presents theoretical and experimental evidence in support of such an irradiation. Doses which can be tolerated by the normal lung are recalled. Data from clinical experience is analyzed and the optimal modalities of irradiation are described. Confirmation of the presumptive effectiveness of radiation therapy can be obtained only through controlled trials such as the one which is ongoing at the EORTC.

[Applications of the normal standard dose in clinical practice]. / Application de la N.S.D. en clinique

On the basis of experience in the François-Baclesse Centre, the practical consequences of the application of the N.S.D. of Ellis are reviewed and in particular : -- the effects of overdose and subdosage in the volume irradiated; -- interpretation of dose at the site of complications; -- the definition of doses of tolerance in critical organs; -- the establishment of optimal dosimetry in the treatment of skin cancers. Despite the approximate character of the exponents used by Ellis and the theoretical discussions which his formula may provoke, it is concluded that it provides the radiotherapist at the present time which a good practical guide and that, within the limitations of the study presented, the clinical results fall within expectations.

[Optimalization of radiotherapy of skin epitheliomas: role of the NSD]. / Optimalisation de la radiothérapie des épithéliomas cutanés: rôle de la N.S.D.

After integration of chronological factors according to Ellis' formula and of B.R.E. for various energies of radiation, the reference dose at the deep limit of the tumor and the surface hyperdosage are kept constant. The values which have been adopted after a very large clinical experience are the following: --reference dose: 6000 rads (N.S.D. 1760). --surface dose: 8400 rads (N.S.D. 2200). The choice of the energy of radiation is the only variation, depending on the thickness of the tumor. A few schemes of equivalent chronological factors are presented, giving less than 1 p. 100 risk of recurrence and a small risk of late radiolesions for normal tissues.