[Estimation of the probability of mediastinal involvement: a statistical definition of the clinical target volume for 3-dimensional conformal radiotherapy in non-small-cell lung cancer?]. / Estimation de la probabilité d'envahissement tumoral médiastinal: une définition statistique du volume-cible anatomoclinique pour la radiothérapie conformationnelle des cancers bronchiques non à petites cellules?

PURPOSE: Conformal irradiation of non-small cell lung carcinoma (NSCLC) is largely based on a precise definition of the nodal clinical target volume (CTVn). The reduction of the number of nodal stations to be irradiated would render tumor dose escalation more achievable. The aim of this work was to design an mathematical tool based on documented data, that would predict the risk of metastatic involvement for each nodal station. METHODS AND MATERIAL: From the large surgical series published in the literature we looked at the main pre-treatment parameters that modify the risk of nodal invasion. The probability of involvement for the 17 nodal stations described by the American Thoracic Society (ATS) was computed from all these publications and then weighted according to the French epidemiological data. Starting from the primitive location of the tumour as the main characteristic, we built a probabilistic tree for each nodal station representing the risk distribution as a function of each tumor feature. From the statistical point of view, we used the inversion of probability trees method described by Weinstein and Feinberg. RESULTS: Taking into account all the different parameters of the pre-treatment staging relative to each level of the ATS map brings up to 20,000 different combinations. The first chosen parameters in the tree were, depending on the tumour location, the histological classification, the metastatic stage, the nodal stage weighted in function of the sensitivity and specificity of the diagnostic examination used (PET scan, CAT scan) and the tumoral stage. A software is proposed to compute a predicted probability of involvement of each nodal station for any given clinical presentation. CONCLUSION: To better define the CTVn in NSCLC 3DRT, we propose a software that evaluates the mediastinal nodal involvement risk from easily accessible individual pre-treatment parameters.

[Which fractionation and radiation dose for non-small-cell bronchial cancers?]. / Quel fractionnement et quelle dose d'irradiation pour les cancers bronchiques non à petites cellules?

The optimal radiation schedule (dose, fractionation, volume) must be adapted to the goal of the treatment: cure with radiation alone or a radiochemotherapy approach or palliation. The former implies to deliver a dose of 60 Gy or more in 6 weeks or an equivalent biological doses. This approach should take into account the different prognostic factors (tumor size, extension...) and the technical possibilities (volume of normal tissue irradiated). Doses above 70 Gy should still be reserved for clinical investigation (conformal radiotherapy).

[Total body irradiation: current indications]. / L'irradiation corporelle totale: les indications actuelles.

The choice of dose and fractionation for total body irradiation is made difficult by the large number of considerations to be taken into account. The outcome of bone marrow transplantation after total body irradiation can be understood in terms of tumour cell killing, engraftment, and normal tissue damage, each of these endpoints being influenced by irradiation-, disease-, transplant-, and patient-related factors. Interpretation of clinical data is further hampered by the overwhelming influence of logistic constraints, the small numbers of randomised studies, and the concomitant variations in total dose and fraction size or dose rate. So far, three cautious conclusions can be drawn in order to tentatively adapt the total body irradiation schedule to clinically-relevant situations. Firstly, the organs at risk for normal tissue damage (lung, liver, lens, kidney) are protected by delivering small doses per fraction at low dose rate. This suggests that, when toxicity is at stake (e.g., in children), fractionated irradiation should be preferred, provided that interfraction intervals are long enough. Secondly, fractionated irradiation should be avoided in case of T-cell depleted transplant, given the high risk of graft rejection in this setting. An alternative would be to increase total (or fractional) dose of fractionated total body irradiation, but this approach is likely to induce more normal tissue toxicity. Thirdly, clinical data have shown higher relapse rates in chronic myeloid leukaemia after fractionated or low dose rate total body irradiation, suggesting that fractionated irradiation should not be recommended, unless total (or fractional) dose is increased. Total body irradiation-containing regimens, primarily cyclophosphamide/total body irradiation, are either equivalent to or better than the chemotherapy-only regimens, primarily busulfan/cyclophosphamide. Busulfan/cyclophosphamide certainly represents a reasonable alternative, especially in patients who may not be eligible for total body irradiation because of prior irradiation to critical organs.

Role of radiation therapy in the treatment of primary tracheal carcinoma.

PURPOSE: The objective of this work is to investigate the role of radiation therapy in the treatment of primary tracheal carcinoma. METHODS AND MATERIALS: From 1963 to 1993, 106 patients presenting with a tracheal carcinoma received a radiation course as part of their treatment in three institutions. Eighty-four patients were treated with megavoltage radiation only, receiving doses ranging from 30 to 70 Gy, with a median dose of 56 Gy. Five patients received high-dose-rate (HDR) brachytherapy, five patients underwent a surgical procedure, and eight received chemotherapy. RESULTS: With a mean follow-up of 141 months, the overall 1-, 2-, and 5-year survival rates are 46%, 21%, and 8%, respectively. Prognostic factors included tumor size (less than 3 cm), performance status, and total radiation dose: the 5-year survival rate dropped from 12% for patients receiving doses greater than 56 Gy to 5% for lower doses. Performance status and radiation doses are the only independent significant factors in multivariate analysis; these results must however be analyzed with precaution in this retrospective study. CONCLUSIONS: Radiation is a good alternative to surgery for primary tracheal cancer. A review of the literature and our current results allow us to recommend a radiation dose greater than 60 Gy for primary irradiation. Collaborative studies are warranted to (1) determine the optimal radiation dose for definitive irradiation, (2) define the potential role of radiation after complete and partial surgery, (3) determine the role and optimal treatment scheme for HDR brachytherapy, (4) describe and record the late effects, (5) establish the potential benefit of chemoradiation.

[Predictive tests of response to radiotherapy. Assessment and perspectives in 1997]. / Les tests prédictifs de la réponse à la radiothérapie: bilan et perspectives en 1997.

The potential tailoring of radiotherapy modalities to the biological characteristics of individual tumours and normal tissues appears to be an exciting way to improve the therapeutic, ratio in radiation therapy patients. Numerous assays have been proposed to provide the clinician with the biological information necessary to predict the outcome after irradiation and to guide the treatment prescription, but none of them has made its way to daily practice. Major difficulties are due to the technical burden of the procedures, the poor characterization of the assayed cells, and, moreover, the high complexity of tumour and normal tissues biology. The present paper reviews the present status of the assessment of tumour cells radiosensitivity, proliferation and oxygenation. Research remains extremely active in the field of biological predictors of response to irradiation. Future steps forwards are expected from progress in the available technologies, (re-)discovery of apoptosis and investigation of normal tissue tolerance.

Toxicity of combined radiation and chemotherapy in non-small cell lung cancer.

The present paper reviews the different acute and late effects due to radiation and chemotherapy on the different organs lying within the chest (lung, esophagus, spinal cord, heart and skin) using available experimental and clinical data. Some specific issues are stressed, such as the problem of time interval between drug and radiation, the latency period for late effects, and the necessity to use an actuarial method to evaluate the real risk of late effects.

[Non small-cell bronchial cancers: toxicity of the association radiotherapy-chemotherapy. Review of the literature]. / Cancers bronchiques non à petites cellules: toxicité de l'association radiothérapie-chimiothérapie. Revue de la littérature.

Radiation therapy is the elective treatment of inoperable non small cell lung cancer, but is potentially curative only for a few of them: failures result from distant metastases and/or from progressive local disease. During the last years, following the progress in chemotherapy, combining radiation and drugs is becoming a more common approach. Nevertheless, one of the main concerns remains the potential interference between both modalities leading to an increased toxicity, which may outweigh all potential benefit. Several organs can be a target for acute or late toxicity: lung (pneumonitis and fibrosis), esophagus (acute esophagitis, stenosis), heart (pericarditis, impaired ventricular functions, heart failure, coronary stenosis), spinal cord (transient myelopathy, radiation myelitis), skin (moist desquamation, fibrosis, telangiectasia). The current published trials combining drug and radiation appear to be a rather safe approach especially when avoiding concomitant treatment. However, several points remain unsolved: the optimal combination scheme, the real risk of late damage observation including the second cancer occurrence risk. This risk is uneasy to evaluate due to the long latency period. The way of describing the late damage is crucial, seeking for a more precise system of evaluating, recording and reporting late effects, taking into account objective damage as well as the patient's symptoms. Therefore, combining drug and radiation should preferentially be performed within prospective studies, with precise evaluation procedures.

Ovarian dysgerminoma: a therapeutic challenge.

Dysgerminoma remains a rare but quite interesting tumor. Over the last 40 years, the prognosis has markedly improved with a 5 year survival increasing from around 30% to more than 80%. Precise diagnosis and adequate staging are mandatory to define the best treatment approach aiming to cure the woman, while preserving her quality of life (ovarian function and fertility).