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Purpose To analyze the efficacy, toxicity, and pattern of relapse after adjuvant cisplatin-based chemotherapy followed by three-dimensional irradiation and concomitant LV5FU2 chemotherapy (high-dose leucovorin and 5-fluorouracil bolus plus continuous infusion) in the treatment of completely resected high-risk gastric cancer. Methods and Materials This was a retrospective analysis of 52 patients with high-risk gastric cancer initially treated by total/partial gastrectomy and lymphadenectomy between January 2002 and June 2007. Median age was 54 years (range, 36–75 years). Postoperative treatment consisted of 5-fluorouracil and cisplatin chemotherapy. Adjuvant chemotherapy was followed by three-dimensional conformal radiotherapy in the tumor bed and regional lymph nodes at 4500 cGy/25 fractions in association with concomitant chemotherapy. Concomitant chemotherapy consisted of a 2-h infusion of leucovorin (200 mg/m²) followed by a bolus of 5-fluorouracil (400 mg/m²) and then a 44-h continuous infusion of 5-fluorouracil (2400–3600 mg/m²) given every 14 days, for three cycles (LV5FU2 protocol). Results Five-year overall and disease-free survival were 50% and 48%, respectively. Distant metastases and peritoneal spread were the most frequent sites of relapse (37% each). After multivariate analysis, only pathologic nodal status was significantly associated with disease-free and overall survival. Acute toxicities were essentially gastrointestinal and hematologic. One myocardial infarction and one pulmonary embolism were also reported. Eighteen patients had a radiotherapy program interruption because of acute toxicity. All patients but 2 have completed radiotherapy. Conclusion Postoperative cisplatin-based chemotherapy followed by conformal radiotherapy in association with concurrent 5-fluorouracil seemed to be feasible and resulted in successful locoregional control.

Resume Le cancer bronchique est le plus meurtrier au monde. Environ 80–85 % sont des carcinomes bronchiques non a petites cellules. Plus d’un tiers sont diagnostiques alors qu’ils sont localement evolues. A ce stade, le traitement de reference reste la chimioradiotherapie concomitante pour les patients en bon etat general. En depit des progres de ces dernieres annees, le pronostic des carcinomes bronchiques non a petites cellules reste defavorable avec des taux eleves de recidives locale et metastatique. L’heterogeneite des anomalies moleculaires presentees par les carcinomes bronchiques non a petites cellules et la connaissance approfondie de ces cibles potentielles est une source prometteuse de developpement de nouveaux agents pharmacologiques. Cet article fait une mise au point sur les voies les plus etudiees, mais aussi celles particulierement prometteuses dans le traitement des bronchiques non a petites cellules localement evolues inoperables. Les etudes les plus avancees en association a la radiotherapie portent sur l’inhibition de la voie d’epidermal growth factor receptor (EGFR) par anticorps monoclonaux et inhibiteurs de tyrosine kinase, et l’inhibition de l’angiogenese. L’essor de ces therapies ciblees permet d’envisager le developpement de combinaisons therapeutiques personnalisees adaptees aux caracteristiques tumorales intrinseques. La modulation pharmacologique de la radiosensibilite par les therapies ciblees n’en est qu’a ses debuts mais offre deja des perspectives encourageantes.

Resume Objectif de l’etude Evaluation de la probabilite de survie sans rechute biochimique apres radiotherapie de rattrapage selon les definitions de l’American society for therapeutic radiology and oncology (Astro) et de Phoenix, chez des patients ayant une persistance ou une elevation secondaire de la concentration serique de PSA, apres prostatectomie pour un cancer de la prostate. Patients et methodes Analyse retrospective des dossiers de 59 patients traites entre 1990 et 2003 par irradiation pour une recidive biochimique apres prostatectomie. Il a ete delivre une dose mediane de 66 Gy dans le lit de prostatectomie par radiotherapie bidimensionnelle ou tridimensionnelle. Le critere principal de jugement de l’efficacite etait la probabilite de survie sans rechute biochimique selon les definitions de l’Astro et de Phoenix (nadir + 2 ng/ml). Resultats Avec un suivi median de 38 mois, la probabilite de survie sans rechute biochimique a trois ans etait selon les criteres de l’Astro de 60 %, elle etait de 72 % selon la definition de Phoenix. Selon l’analyse unifactorielle, une concentration serique de PSA ≥ 1 ng/ml avant la radiotherapie et un envahissement des vesicules seminales etaient associes a un risque de recidive biochimique. Selon l’analyse multifactorielle, seule une concentration serique de PSA ≥ 1 ng/ml avant la radiotherapie reste predictive pour une recidive biochimique, quelle que soit la definition. Conclusion La radiotherapie de rattrapage est un traitement efficace apres prostatectomie, que l’on utilise la definition de l’Astro ou celle de Phoenix. Seule une concentration serique de PSA ≥ 1 ng/ml avant la radiotherapie est predictive pour la recidive biochimique.

As compared to conventional axillary dissection, the sentinel node technique is accompanied by reduced morbidity and shorter hospital stay. Based on available data, the use of this technique does not seem to yield higher rates of axillary recurrence. A combination of both radioisotope detection and blue dye increases the identification rate, while also reducing false-negative rate. Surgical results are optimized when preoperative lymphoscintigraphy mapping is obtained in addition to peroperative probe detection. Considering the site of injection, the subareolar injection can be easy to apply even in case of non-palpable tumours, and gives higher count rates. However, the intraparenchymal, peritumoral, injection is necessary to evidence cases of extra-axillary drainage (internal mammary, infra- or supraclavicular) that is present in about 20% of patients. With the advent of hybrid cameras (SPECT-CT), the topography of these extra-axillary nodes can be given with high precision. Use of the sentinel node technique has been accompanied by an increase in the percent of patients with node involvement, due to an increased detection of micrometastases inferior or equal to 2 mm. Following an overview of basic principles, and of the main results with the sentinel node technique we focus the discussion on several points that are still open to debate, such as: 1) which group of patients can benefit from the sentinel node technique? 2) What is the optimal methodology? 3) What is the prognostic significance of micrometastases and of isolated tumour cells? 4) What attention should be given to extra-axillary drainage?

Resume Objectif de l’etude Etude de la faisabilite et des resultats d’une chimiotherapie adjuvante suivie d’une chimioradiotherapie realisee selon une technique conformationnelle chez des patients operes pour un adenocarcinome gastrique. Patients et methodes Vingt-six patients ont recu apres une chirurgie radicale (classee R0 ou R1) trois cycles de 5-fluoro-uracile et cisplatine, puis une chimioradiotherapie associant le protocole LV5FU2 et une radiotherapie de 45 Gy. Resultats Soixante-dix-sept pour cent des patients etaient atteints d’un cancer classe pT3 ou pT4 et les ganglions ont ete classes pN1 dans 54 % des cas et pN2 dans 31 %. Faisabilite Il a ete observe durant la chimiotherapie adjuvante, qui a pu etre menee a son terme dans tous les cas sauf un, des nausees ou des vomissements de grade II ou III chez 12 patients (48 %) et une neutropenie de grade III ou IV chez deux patients. Il a ete observe pendant la chimioradiotherapie des nausees ou vomissements de grade II ou III chez dix patients, une diarrhee de grade II ou III chez deux et une œsophagite de grade II ou III chez deux. Tous les patients, sauf un, ont recu la dose prevue de 45 Gy. La radiotherapie a ete interrompue chez six patients pendant en moyenne 14 jours. Apres un suivi moyen de 30 mois, 65 % des patients etaient en vie sans rechute et la duree mediane de survie etait de 32 mois. Conclusion Ce schema parait faisable et permet d’intensifier la chimiotherapie postoperatoire par rapport au schema de type Macdonald. Son benefice clinique reste a evaluer dans une etude de phase III.

Results of surgery in locally advanced esophageal carcinomas (T3 and/or N1) are disappointing. Concomitant chemoradiotherapy (RTCT) gave equivalent survival results in many phase II studies. Two randomized trials (French and German) compared surgery or additional RTCT after a first phase of RTCT. Both drew the same conclusions, that is surgery did not improve overall survival but increased postoperative mortality. However, local control was found better in the surgical arms, and in some subgroups, esophagectomy improved disease-free survival suggesting that some patients may benefit from surgery. After preoperative RTCT, absence of residual disease in the surgical specimen (pathological complete response) occurs in 15 to 30%; these patients underwent a radical surgery without any benefit but with high risk of morbidity and mortality. Nevertheless, it is still difficult to select this sub-population: CT-scan or endoscopy with biopsies have a low sensitivity and specificity. 18-FDG-PET-scan, performed after or during the RTCT, is able to increase sensitivity, but only preliminary results with small populations are available. No biological factor of chemoradiosensitivity (p53, NfkappaB, p21...) could predict who will respond or not. Another approach is to reserve surgery only to patients with a demonstrated local failure (salvage surgery) but the feasibility of this technique is still debated. Finally, local relapses are frequent after RTCT and optimisation of the current schedules is mandatory to improve oncologic results. Unfortunately, increasing the radiation dose did not improve local control and showed more toxicities. New drugs as taxanes, oxaliplatine, or targeted therapies are tested in on-going phase III trial.

Postoperative radiotherapy after breast surgery increases overall survival by decreasing the local relapse rate. The main site of relapse is the breast or the chest wall. The value of irradiation of the nodal basins is still discussed. It must be emphasized that nodal areas were systematically irradiated in the postmastectomy randomized trials demonstrating a benefit in survival for adjuvant radiotherapy. Axillary relapses are infrequent in case of complete axillary dissection; complementary irradiation could be proposed if the axillary dissection is incomplete or if there is a massive pathologic involvement of the axilla. Its main complication is lymphoedema, which remains the most frequent sequellae of the treatment of breast cancer. Supraclavicular irradiation is logical in case of axillary involvement. Internal mammary nodes are involved in 20 to 40% of the patients, depending of the axillary involvement and location of the tumor inside the breast. Irradiation of the internal mammary basin is difficult: optimal dosimetry required a CT-based simulation. Its benefit remains to be proved. Internal mammary nodes irradiation probably increased cardiovascular mortality. Sophisticated techniques are needed to spare the heart from irradiation. Two large randomized trials (French group, European Organization for Research and Treatment of Cancer [EORTC]) are currently evaluating the possible benefit of internal mammary irradiation.

Tres estudios aleatorizados recientes han demostrado un beneficio, en terminos de supervivencia sin progresion biologica y clinica, de la radioterapia adyuvante tras una prostatectomia, en los pacientes con riesgo de recidiva local como una afectacion extracapsular, una invasion de las vesiculas seminales o margenes de exeresis positivos. Sin embargo, estos tres estudios han comparado una radioterapia adyuvante con una actitud de vigilancia, y no con la administracion precoz de radioterapia en caso de recidiva biologica, es decir, con una concentracion de antigeno prostatico especifico (PSA) muy baja (por ejemplo, ≤ 0,6 ng/ml) sin signos clinicos de la enfermedad, lo que expone a una parte de estos pacientes a un riesgo de sobretratamiento con un riesgo de complicacion. Varios estudios retrospectivos han demostrado el beneficio, en terminos de control biologico, de una radioterapia de rescate en caso de reelevacion del PSA tras una negativizacion inicial del PSA postoperatorio, la cual es mas eficaz cuanto mas precoz sea. Sin embargo, a la vista de los estudios controlados que favorecen la radioterapia adyuvante, esta se convierte en el tratamiento estandar tras la prostatectomia si existen factores de riesgo de recidiva local (margenes positivos, afectacion extracapsular o de las vesiculas seminales). En la actualidad se estan realizando varios estudios aleatorizados para definir el papel que ocupa la radioterapia diferida respecto a la radioterapia adyuvante.

A number of retrospective and prospective studies have demonstrated that radiotherapy of prostate cancer must be actually conformal. Three-dimensional (3D) treatment planning consists in an as accurate as possible definition of target-volume, usually by CT-scan, and design of radiation fields shaped to this target-volume. Several steps are required, each step being important for the overall quality of the treatment. Conformal radiotherapy is better tolerated than conventional irradiation, with significantly less rectal toxicity. It allows dose-escalation up to 80 Gy. It is now possible to go beyond this dose with intensity-modulated radiotherapy. The benefit of these high doses was demonstrated by some large retrospective studies and some prospective dose-escalation trials. Several randomized trials are in progress, preliminary results of two of them have been published, both showing an improvement in disease control with the higher doses. The advantage of higher doses is clearly evident for patients in the intermediate prognostic group, but is still discussed for patients with a low risk tumour or treated in combination with hormone therapy. Late proctitis is the main toxicity of these high doses. Some volume constraints have been defined during the last years and will allow a decrease of the rate of rectal toxicity. Because of these technological improvements, results of radiation therapy are now similar to those of surgery: no direct comparison with a randomized trial is available, but large comparative studies show that long-term disease control are identical with both techniques. Radiation therapy must be proposed to all patients with a prostate carcinoma as an alternative to surgery.

Purpose: To evaluate outcomes after high-dose-rate endobronchial brachytherapy (HDR-EBBT) for limited lung carcinoma. Methods: A total of 106 patients with endobronchial lung cancer and not eligible for surgery or external beam radiotherapy, without nodal or visceral metastases, were treated with HDR-EBBT. They had developed disease relapse after surgery ( n = 43) or external beam radiotherapy ( n = 27) or had early lung cancer with respiratory insufficiency ( n = 36). Treatment consisted of six fractions of 5 or 7 Gy, usually delivered 1 cm from the source. Results: The complete histologic response rate, evaluated at 3 months after HDR-EBBT, was 59.4%. At 3 and 5 years, the local control, overall survival, and cause-specific survival rates were 60.3% and 51.6%, 47.4 and 24%, and 67.9 and 48.5%, respectively. Factors significantly associated with local failure were high tumor volume (tumor length >2 cm, bronchial obstruction >25%, tumor visibility on CT scan) and previous endoscopic treatment. Cause-specific survival, but not overall survival, was significantly associated with local control, probably because of the high rate of deaths not related to lung cancer. Five deaths were attributed to the HDR-EBBT procedure (two from fatal hemoptysis and three from bronchial necrosis). Conclusion: High-dose-rate-EBBT achieved a long-term cause-specific survival rate of 50% of the patients with localized endobronchial carcinoma and could be considered curative.

A number of retrospective and prospective studies have demonstrated that radiotherapy of prostate cancer must be actually conformal. Three-dimensional (3D) treatment planning consists in an as accurate as possible definition of target-volume, usually by CT-scan, and design of radiation fields shaped to this target-volume. Several steps are required, each step being important for the overall quality of the treatment. Conformal radiotherapy is better tolerated than conventional irradiation, with significantly less rectal toxicity. It allows dose-escalation up to 80 Gy. It is now possible to go beyond this dose with intensity-modulated radiotherapy. The benefit of these high doses was demonstrated by some large retrospective studies and some prospective dose-escalation trials. Several randomized trials are in progress, preliminary results of two of them have been published, both showing an improvement in disease control with the higher doses. The advantage of higher doses is clearly evident for patients in the intermediate prognostic group, but is still discussed for patients with a low risk tumour or treated in combination with hormone therapy. Late proctitis is the main toxicity of these high doses. Some volume constraints have been defined during the last years and will allow a decrease of the rate of rectal toxicity. Because of these technological improvements, results of radiation therapy are now similar to those of surgery: no direct comparison with a randomized trial is available, but large comparative studies show that long-term disease control are identical with both techniques. Radiation therapy must be proposed to all patients with a prostate carcinoma as an alternative to surgery.

La radioterapia actual del cancer de prostata solo puede ser conformacional. Consiste en la localizacion de la prostata mediante tomografia computarizada y en una adaptacion lo mas precisa posible de los haces de irradiacion al volumen-diana. Requiere una sucesion de etapas tecnicas cuya practica exacta condiciona la calidad del conjunto. Esta tecnica ha demostrado una mejor tolerancia que la radioterapia convencional, con menos efectos secundarios de manera significativa, en especial rectales. Permite aumentar las dosis sobre la prostata hasta un valor de 80 Gy. Este umbral de 80 Gy sera superado probablemente por la radioterapia de intensidad modulada. El beneficio de las dosis elevadas se ha demostrado en importantes estudios prospectivos de ajuste progresivo de la dosis. Dos ensayos aleatorizados publicados se situan tambien a favor de las dosis elevadas, y existen otros en desarrollo. La utilidad de las dosis elevadas estaria demostrada en los pacientes de los grupos intermedios. Es motivo de discusion en los pacientes con riesgo bajo, o bien en los tratados en asociacion con la hormonoterapia. La toxicidad principal es rectal; de manera progresiva, se han demostrado imposiciones volumetricas que, en el futuro, deberian permitir disminuir aun mas dicha toxicidad. Gracias a los progresos realizados con la tecnica conformacional, los resultados obtenidos son similares a los de la cirugia en terminos de control de la enfermedad, como se ha demostrado en varias series comparativas. Por tanto, la radioterapia se ha convertido en una alternativa real a la cirugia y debe proponerse a todo paciente con cancer de la prostata.

Initially, preoperative chemotherapy had three aims, to improve the overall survival by an early exposure to systemic therapy, to evaluate in vivo the efficacy of chemotherapy and to monitor post-operative treatment, and to increase the rate of breast-conserving treatments. Eight randomised trials have been published. The general consensus about the results of these trials is that neoadjuvant chemotherapy did not improve overall survival, in comparison with an adjuvant treatment. Clinical and especially pathological complete response rates were correlated with the outcome of the patients and could be considered as an independent prognostic factor. Primary chemotherapy is a powerful tool to study the predictive factors, especially biological factors, of chemosensitivity. However, the usefulness of this approach to adjust post-operative treatments remains to be demonstrated. Finally, primary chemotherapy slightly increased the rate of breast conserving treatments, but is accompanied by a small increase in the risk of local recurrence. To propose a conservative treatment to a woman initially not suitable for a lumpectomy needs clear information about this enhanced risk.

The endobronchial brachytherapy procedure involves the insertion of an afterloading catheter into bronchus in close proximity to an endoluminal lesion, and to perform limited irradiation sparing as much as possible normal health tissues. The catheter is inserted during a classical flexible bronchoscopy. Three types of indications have been discussed: (i) palliative treatment of lung carcinoma, with or without laser desobstruction: an improvement in respiratory symptoms was observed in 60 to 80% of the cases; (ii) curative treatment for localised endobronchial carcinomas, in previously irradiated patients, or in case of contraindication of surgery or external beam irradiation; local control rate range from 60 to 70% at 2 years; (iii) combination of external irradiation and brachytherapy in the first line treatment of lung cancers. Two randomised trials did not show any improvement in survival for this approach; however, they have included advanced diseases. In the opposite, this association seems very effective for early stage lung carcinomas. Two major complications were regularly reported, haemoptysis and radiation bronchitis. Predictive factors for these toxicities are actually better known: haemoptysis could be due to a progressive disease more often than to brachytherapy itself; technical factors (dose, volume, fractionation), however, could explain a number of radiation bronchitis, and their incidence could decrease in the future.

Resume La rechute biochimique, apres prostatectomie, n’est pas exceptionnelle, touchant selon les series 20 a 40 % des malades operes. Pour la prevenir, certains associent a la chirurgie une irradiation adjuvante, immediatement apres la chirurgie. Aucune etude de phase III n’est venue confirmer cette attitude. Les indications preferentielles d’une irradiation adjuvante sont une extension extra-capsulaire pluri-focale et l’atteinte des tranches de section, retrouvee sur plusieurs niveaux de coupe. L’analyse des series historiques laisse a penser que, dans ce cas, le controle biochimique de la maladie est ameliore. Plutot que d’irradier immediatement apres la chirurgie, d’autres preferent atteindre la reascension du PSA, afin de ne pas surtraiter certains patients. La radiotherapie, dite alors de sauvetage, donne 40 a 70 % de normalisations du PSA, mais elle ne semble reellement efficace que si la concentration serique de PSA est faible au moment du traitement. La radiotherapie differee n’est donc justifiee, en cas de facteurs de risque de recidive locale, que sous couvert d’une surveillance rapprochee du PSA apres la chirurgie. Dans tous les cas, il est important d’essayer de differencier risque de rechute locale et de dissemination metastatique : il est clair qu’une atteinte ganglionnaire histologiquement prouvee au moment de la chirurgie est plutot le signe de la presence de micro-metastases. Ceci semble egalement etre le cas si les vesicules seminales sont atteintes sur la piece operatoire, quoique ceci reste a confirmer.

Background: To evaluate the results of chemoradiotherapy with or without surgery in locally-advanced esophageal carcinomas (T3 and/or nodal involvement). Methods: One hundred twelve patients with locally-advanced carcinoma of the esophagus without histologically proven invasion of the tracheobronchial tree or distant visceral metastases were treated with concomitant chemoradiotherapy followed by re-evaluation; surgery was performed or chemoradiotherapy continued, based on tumor regression and the patient's general status. Chemoradiotherapy consisted of concomitant 5-fluorouracil (5FU)(1 g/m 2 day 1–3), cisplatinum (50 mg/m 2 day 1 and 2), and external beam irradiation up to a dose of 40 or 43.2 Gy. After a 4-week rest period, radical esophagectomy or a new cycle of chemoradiotherapy (up to a total dose of 65 Gy) was performed. Results: A complete clinical response was obtained in 25.7% of the patients and a partial response in 45.9%. Fifty patients underwent surgery, but only 38 patients had an esophagectomy. Post-esophagectomy mortality was 5.3%. A complete histologic response rate of 23.7% was obtained. Two- and 5-year survival rates were, respectively, 41.5% and 28.6% for the whole population. According to multivariate analysis, prognostic factors for survival were Karnofsky index, esophagectomy, and response to chemoradiotherapy. Five-year survival for patients who experienced a partial response to radiation and chemotherapy was 49.1% for those who had surgery and 23.5% for those treated without surgery ( p = 0.003). There was no obvious benefit for the small number of patients treated surgically after complete response to radiation and chemotherapy. Toxicity, essentially hematologic, was moderate. Conclusion: For locally-advanced esophageal carcinomas, esophagectomy, after concomitant chemoradiotherapy, could improve the survival rate, especially for patients who responded partially to the latter.

Resume But du protocole Le pronostic des cancers bronchiques localises au thorax mais inoperables reste sombre. Nous avons realise une etude de phase II de radio-chimiotherapie concomitante avec pour but d'ameliorer le controle local et la survie sans metastases a distance. Materiel et methodes Trente neuf patients ont ete inclus dans cette etude (dont 3 femmes; âge moyen: 56 ans). Quatre-vingt quinze pour cent avaient un bon etat general (indice de l'OMS 0 ou 1); il s'agissait d'un carcinome epidermoide dans 64 % des cas. On denombrait une tumeur de stade 1, 9 de stade IIIA, 24 de stade IIIB et 2 de stade inconnu. Le protocole consistait en des cycles de trois semaines de cisplatine (CDDP) (50 mg/m2 a j1 et j2) 5-fluoro-uracile (5FU) (1 gr/m2 a j1, j2 et j3 en perfusion continue) et de radiotherapie externe (20 Gy en dix fractions de j1 a j12), avec un repos therapeutique la 3e semaine. Resultats La tolerance du traitement a ete dans l'ensemble satisfaisante, il a ete observe une leucopenie de grade 3 ou 4 dans 15 % des cas, une thrombopenie de grade 3 ou 4 dans 3 % des cas, des nausees ou des vomissements de grade 3 ou 4 dans 15 % des cas. Nous n'avons pas note d'œsophagite majeure. La dose de chimiotherapie a pu etre respectee dans plus de 90 % des cycles. Une reponse objective a ete obtenue chez 56 % des patients, avec seulement 3 % de reponses completes. Cependant, l'evaluation etait faite en moyenne 6 semaines apres la fin du traitement et la fibrose post-radique a pu gener l'interpretation des images. La mediane et les taux de survie a 2 et 3 ans etaient respectivement de 11,4 mois, 27 % et 14 %. Le seul facteur pronostique retrouve etait l'indice d'etat general de l'OMS. La reponse radiologique n'etait pas un critere pronostique. Les modes de rechute ont ete analyses chez 20 patients: rechute locale isolee: 6 cas; metastases: 13 cas; association des deux: 1 cas. Conclusion Les associations concomitantes 5-FUCDDP et radiotherapie externe semblent realisables en pratique quotidienne. L'evaluation doit porter sur la survie et non sur la reponse radiologique. Une amelioration du controle local semble egalement realisable avec ce type d'association.

Resume But de l'etude Une obstruction tumorale endobronchique est frequemment notee au cours de l'evolution des cancers bronchiques, et peut etre responsable de symptomes gravissimes. Les patients peuvent se voir proposer une desobstruction bronchique pour laquelle plusieurs techniques sont aujourd'hui disponibles. Patients et methodes Une curietherapie endobronchique a ete realisee chez 149 malades. Soixante treize malades ont ete traites dans une optique curative, 47 dans un but palliatif et 29 ont recu une irradiation endobronchique en complement d'une irradiation externe. Le traitement consistait en series, repetees tous les 15 jours, jusqu'a un maximum de trois series, comportant deux seances a 24 h d'intervalle, delivrant chacune une irradiation de 7 Gy a 1 cm du catheter. Resultats Tous signes fonctionnnels confondus, 79 % des patients ont beneficie d'un effet palliatif sur leur Symptomatologie. Cent trente-deux patients ont eu une evaluation par endoscopie 2 mois apres le traitement; 64 tumeurs (48,5 %) etaient en remision histologique complete. La mediane de survie etait de 14,4 mois pour les patients traites a visee curative. L'obtention d'une remission histologique permettait de predire une survie plus longue (mediane de survie: 26,5 mois). Onze hemoptysies massives et 13 bronchites radiques ont ete observees. Conclusion Ces resultats confirment la faisabilite et les bons resultats de l'irradiation endobronchique sur ce terrain et incitent a promouvoir la realisation d'essais multicentriques controles, afin que soit precisee la place de la curietherapie endobronchique dans la strategie therapeutique des cancers bronchiques.

Lung cancer is the leading cause of cancer-related death. Between 80-85% of lung cancers are non-small cell lung carcinomas. One third of the patients are diagnosed with locally advanced stage. In this condition, concomitant radio-chemotherapy is the standard treatment for patients with good performance status. Despite important improvements in the last years, non-small cell lung carcinoma prognosis remains poor, with high rates of both local recurrences and metastases. The heterogeneity of molecular characteristics of non-small cell lung carcinoma cells and a better knowledge of potential targets offer promising developments for new pharmacologic agents. Hereafter we will review the currently most studied pathways and the most promising ones for the treatment of locally advanced unresectable non-small cell lung carcinoma. Two of the most attractive pathways where new agents have been developed and assessed in combination with thoracic radiotherapy or radiochemotherapy are the EGFR pathway (either with the use of monoclonal antibodies or tyrosine kinase inhibitors) and the angiogenesis inhibition. The development of targeted agents could lead to individualized therapeutic combinations taking into account the intrinsic characteristics of tumor cells. Pharmacological modulation of tumour cells radiosensitivity by targeted therapies is only starting, but yet offers promising perspectives.

Given the risk of undesired toxicity, prophylactic internal mammary (IM) chain irradiation should be offered only to patients at high risk of occult involvement. Lymphoscintigraphy for axillary sentinel node biopsy might help in selecting these patients.We reviewed published studies with the following selection criteria: ≥ 300 breast cancer patients referred for axilla sentinel node biopsy; scintigraphy performed after peritumoral or intratumoral tracer injection; IM biopsy in the case of IM drainage; and axilla staged routinely independent of IM status.Six prospective studies, for a total of 3,876 patients, fulfilled the inclusion criteria. Parasternal drainage was present in 792 patients (20.4%). IM biopsy was performed in 644 patients and was positive in 111 (17.2%). Of the positive IM biopsies, 40% were associated with tumors in the lateral breast quadrants. A major difference in the IM positivity rate was found according to the axilla sentinel node status. In patients with negative axilla, the IM biopsy was positive in 7.8% of cases. In patients with positive axilla, however, the IM biopsy was positive in 41% (p.00001). Because biopsy of multiple IM hot nodes is difficult, the true risk could be even greater, probably close to 50%.Patients with IM drainage on lymphoscintigraphy and a positive axilla sentinel node have a high risk of occult IM involvement. These women should be considered for IM radiotherapy.

As compared to conventional axillary dissection, the sentinel node technique is accompanied by reduced morbidity and shorter hospital stay. Based on available data, the use of this technique does not seem to yield higher rates of axillary recurrence. A combination of both radioisotope detection and blue dye increases the identification rate, while also reducing false-negative rate. Surgical results are optimized when preoperative lymphoscintigraphy mapping is obtained in addition to peroperative probe detection. Considering the site of injection, the subareolar injection can be easy to apply even in case of non-palpable tumours, and gives higher count rates. However, the intraparenchymal, peritumoral, injection is necessary to evidence cases of extra-axillary drainage (internal mammary, infra- or supraclavicular) that is present in about 20% of patients. With the advent of hybrid cameras (SPECT-CT), the topography of these extra-axillary nodes can be given with high precision. Use of the sentinel node technique has been accompanied by an increase in the percent of patients with node involvement, due to an increased detection of micrometastases inferior or equal to 2 mm. Following an overview of basic principles, and of the main results with the sentinel node technique we focus the discussion on several points that are still open to debate, such as: 1) which group of patients can benefit from the sentinel node technique? 2) What is the optimal methodology? 3) What is the prognostic significance of micrometastases and of isolated tumour cells? 4) What attention should be given to extra-axillary drainage?

Between January 1973 and December 1984, 55 patients with prior irradiation of the oropharynx underwent salvage irradiation for recurrent (26 patients) or second cancers (29 patients) of the base of tongue. The initial irradiation had delivered from 45 to 80 Gy to the base of tongue. One of two techniques of Iridium implantation was used for salvage. Single course implants, delivering 60 Gy, were used until June 1981 in a total of 31 patients. After June 1981, split course implants with a source shift were used in 24 patients in the hope of decreasing treatment complications. The first and second course of the split course implants delivered 35 and 30 Gy, respectively, at a 1-month interval. The active lines of the second implant were placed parallel to and between the position of the lines of the first implant. This shift in the source position resulted in a more uniform dose within the treated volume with a 60% reduction in the high dose sleeves. The overall 3-year survival was 19% (28% T less than or equal to 3 cm). The overall local failure rate was 45.5% (25/55). The difference between the local failure rate after single course implants (52%) and after split course implants (37.5%) was not statistically significative. The response observed after the first course of a split course implant proved to be a reliable indication of the probability of achieving local control after a full course of treatment: 2/14 failures (14%) if the response was greater than or equal to 75% versus 7/10 (70%) if the response was less than 75% (p less than 0.01). The only complication noted in the 40 patients achieving immediate local control after either implant technique was mucosal necrosis. The introduction of split course implants was followed by a two and a half fold decrease in the incidence of necrosis: 43% (9/21) in the single course group and 16% (3/19) in the split course group (p = 0.05). Interstitial brachytherapy offers an effective and reasonable option for salvage therapy in patients with recurrent and second cancers occurring in the base of tongue even when the tumor arises in a zone that has previously received high dose irradiation. The use of split course implants with a shift in the position of the active lines at the time of the second implant significantly decreases the risk of radionecrosis.

Postoperative radiotherapy after breast surgery increases overall survival by decreasing the local relapse rate. The main site of relapse is the breast or the chest wall. The value of irradiation of the nodal basins is still discussed. It must be emphasized that nodal areas were systematically irradiated in the postmastectomy randomized trials demonstrating a benefit in survival for adjuvant radiotherapy. Axillary relapses are infrequent in case of complete axillary dissection; complementary irradiation could be proposed if the axillary dissection is incomplete or if there is a massive pathologic involvement of the axilla. Its main complication is lymphoedema, which remains the most frequent sequellae of the treatment of breast cancer. Supraclavicular irradiation is logical in case of axillary involvement. Internal mammary nodes are involved in 20 to 40% of the patients, depending of the axillary involvement and location of the tumor inside the breast. Irradiation of the internal mammary basin is difficult: optimal dosimetry required a CT-based simulation. Its benefit remains to be proved. Internal mammary nodes irradiation probably increased cardiovascular mortality. Sophisticated techniques are needed to spare the heart from irradiation. Two large randomized trials (French group, European Organization for Research and Treatment of Cancer [EORTC]) are currently evaluating the possible benefit of internal mammary irradiation.

Results of surgery in locally advanced esophageal carcinomas (T3 and/or N1) are disappointing. Concomitant chemoradiotherapy (RTCT) gave equivalent survival results in many phase II studies. Two randomized trials (French and German) compared surgery or additional RTCT after a first phase of RTCT. Both drew the same conclusions, that is surgery did not improve overall survival but increased postoperative mortality. However, local control was found better in the surgical arms, and in some subgroups, esophagectomy improved disease-free survival suggesting that some patients may benefit from surgery. After preoperative RTCT, absence of residual disease in the surgical specimen (pathological complete response) occurs in 15 to 30%; these patients underwent a radical surgery without any benefit but with high risk of morbidity and mortality. Nevertheless, it is still difficult to select this sub-population: CT-scan or endoscopy with biopsies have a low sensitivity and specificity. 18-FDG-PET-scan, performed after or during the RTCT, is able to increase sensitivity, but only preliminary results with small populations are available. No biological factor of chemoradiosensitivity (p53, NfkappaB, p21...) could predict who will respond or not. Another approach is to reserve surgery only to patients with a demonstrated local failure (salvage surgery) but the feasibility of this technique is still debated. Finally, local relapses are frequent after RTCT and optimisation of the current schedules is mandatory to improve oncologic results. Unfortunately, increasing the radiation dose did not improve local control and showed more toxicities. New drugs as taxanes, oxaliplatine, or targeted therapies are tested in on-going phase III trial.

Study about the efficacy of salvage radiotherapy (RT), in terms of biochemical disease free survival (bDFS), according to ASTRO and Phoenix (nadir+2) definitions, for persistent or rising PSA after radical prostatectomy.Retrospective analysis of 59 patients who underwent RT between 1990 and 2003 for PSA recurrence after radical prostatectomy. Patients received a median of 66Gy to the prostate bed with 3D or 2D RT. The main end point was bDFS according to ASTRO and Phoenix (nadir+2) definitions. Different criterion sets were analysed to calculate bDFS and pretreatment factors that might predict biochemical relapse were sought for each.After a 38-month median follow-up, the 3-year bDFS rates were: 60 and 72% for ASTRO and Phoenix (nadir+2 ng/ml) definitions respectively. According to univariate analysis, pre-RT PSAor =1 ng/ml and seminal vesicle involvement were associated with biochemical relapse. Multivariate analysis retained only pre-RT PSAor =1 ng/ml as an independent predictor of biochemical relapse for the two definitions.Salvage RT is an effective treatment after radical prostatectomy according to ASTRO or Phoenix definitions. Only pre-RT PSAor =1 ng/ml predicted relapse.

Analysis of the feasibility and results of adjuvant chemotherapy followed by conformal chemoradiotherapy after surgery for gastric carcinoma.Twenty-six patients (R0 or R1) were treated postoperatively by three cycles of 5-fluorouracil (5-FU) and cisplatin, followed by a concomitant association of LV5FU2 chemotherapy with a conformal radiotherapy of 45 Gy.The tumor was classified pT3-T4 in 77% of the patients and 92.5% had a nodal involvement (pN1: 54%; pN2: 31%).(1) Adjuvant chemotherapy: nausea/vomiting grade II/III: 12 patients (48%); neutropenia grade III/IV: two patients; completed in all patients, except one. (2) Chemoradiotherapy: nausea/vomiting grade II/III: 10 patients; diarrhea grade II/3: two patients; oesophagitis grade II/III: two patients; myocardial infarction/pulmonary embolism: two patients. All patients except one received the planned dose of 45Gy. Radiotherapy was interrupted in six cases, with a median duration of 14 days. Survival: with a median follow-up of 30 months, 65% of the patients were alive without disease; median survival was 32 months.This postoperative schedule was judged feasible. It allowed the deliverance of a more intensified chemotherapy than the classical schedule. Its clinical benefit must be evaluated in a phase III trial.

Background To assess the efficacy of salvage radiotherapy (RT) for persistent or rising PSA after radical prostatectomy and to determine prognostic factors identifying patients who may benefit from salvage RT. Methods Between 1990 and 2003, 59 patients underwent RT for PSA recurrence after radical prostatectomy. Patients received a median of 66 Gy to the prostate bed with 3D or 2D RT. The main end point was biochemical failure after salvage RT, defined as an increase of the serum PSA value >0.2 ng/ml confirmed by a second elevation. Results Median follow-up was 38 months. The 3-year and 5-year bDFS rates were 56.1% and 41.2% respectively. According to multivariate analysis, only preRT PSA ≥1 ng/ml was associated with biochemical relapse. Conclusion When delivered early, RT is an effective treatment after radical prostatectomy. Only preRT PSA ≥1 ng/ml predicted relapse.

A number of retrospective and prospective studies have demonstrated that radiotherapy of prostate cancer must be actually conformal. Three-dimensional (3D) treatment planning consists in an as accurate as possible definition of target-volume, usually by CT-scan, and design of radiation fields shaped to this target-volume. Several steps are required, each step being important for the overall quality of the treatment. Conformal radiotherapy is better tolerated than conventional irradiation, with significantly less rectal toxicity. It allows dose-escalation up to 80 Gy. It is now possible to go beyond this dose with intensity-modulated radiotherapy. The benefit of these high doses was demonstrated by some large retrospective studies and some prospective dose-escalation trials. Several randomized trials are in progress, preliminary results of two of them have been published, both showing an improvement in disease control with the higher doses. The advantage of higher doses is clearly evident for patients in the intermediate prognostic group, but is still discussed for patients with a low risk tumour or treated in combination with hormone therapy. Late proctitis is the main toxicity of these high doses. Some volume constraints have been defined during the last years and will allow a decrease of the rate of rectal toxicity. Because of these technological improvements, results of radiation therapy are now similar to those of surgery: no direct comparison with a randomized trial is available, but large comparative studies show that long-term disease control are identical with both techniques. Radiation therapy must be proposed to all patients with a prostate carcinoma as an alternative to surgery.

Anal carcinoma, a common disease in HIV-positive patients, is usually treated with chemoradiotherapy. Generally tolerance was poor before the availability of highly active antiretroviral therapies. We report our experience of treating anal carcinoma in the era of new antiviral drugs.Between 1997 and 2001, nine men on highly active antiretroviral therapies with good immune status before chemoradiotherapy received concomitant chemoradiotherapy consisting of 5-fluorouracil and cisplatinum, and high-dose radiotherapy (60-70 Gy) for anal carcinoma. Six cancers were Stage I, two were Stage II, and one was Stage III. CD4+ cell counts were200/ml for four patients, between 200/ml and 500/ml for four, and500/ml for one.All patients received the planned dose of radiation (or = 60 Gy). The chemotherapy dose was reduced 25 percent in six patients. Overall treatment time was 58 days. Grade 3 hematologic or skin toxicity occurred in four patients. No association was observed between high-grade toxicity and CD4+ cell count. None of the patients developed opportunistic infections during follow-up. Eight patients were disease-free after a median follow-up of 33 months. Among them, four had no or minor anal function impairment at the last follow-up visit. One patient with T4N2 disease relapsed locally one year after treatment and underwent salvage abdominoperineal excision.High-dose chemoradiotherapy for anal carcinomas is feasible with low toxicity in HIV-positive patients treated with highly active antiretroviral therapies. Local control is similar to that obtained for HIV-negative patients.

Initially, preoperative chemotherapy had three aims, to improve the overall survival by an early exposure to systemic therapy, to evaluate in vivo the efficacy of chemotherapy and to monitor post-operative treatment, and to increase the rate of breast-conserving treatments. Eight randomised trials have been published. The general consensus about the results of these trials is that neoadjuvant chemotherapy did not improve overall survival, in comparison with an adjuvant treatment. Clinical and especially pathological complete response rates were correlated with the outcome of the patients and could be considered as an independent prognostic factor. Primary chemotherapy is a powerful tool to study the predictive factors, especially biological factors, of chemosensitivity. However, the usefulness of this approach to adjust post-operative treatments remains to be demonstrated. Finally, primary chemotherapy slightly increased the rate of breast conserving treatments, but is accompanied by a small increase in the risk of local recurrence. To propose a conservative treatment to a woman initially not suitable for a lumpectomy needs clear information about this enhanced risk.

The endobronchial brachytherapy procedure involves the insertion of an afterloading catheter into bronchus in close proximity to an endoluminal lesion, and to perform limited irradiation sparing as much as possible normal health tissues. The catheter is inserted during a classical flexible bronchoscopy. Three types of indications have been discussed: (i) palliative treatment of lung carcinoma, with or without laser desobstruction: an improvement in respiratory symptoms was observed in 60 to 80% of the cases; (ii) curative treatment for localised endobronchial carcinomas, in previously irradiated patients, or in case of contraindication of surgery or external beam irradiation; local control rate range from 60 to 70% at 2 years; (iii) combination of external irradiation and brachytherapy in the first line treatment of lung cancers. Two randomised trials did not show any improvement in survival for this approach; however, they have included advanced diseases. In the opposite, this association seems very effective for early stage lung carcinomas. Two major complications were regularly reported, haemoptysis and radiation bronchitis. Predictive factors for these toxicities are actually better known: haemoptysis could be due to a progressive disease more often than to brachytherapy itself; technical factors (dose, volume, fractionation), however, could explain a number of radiation bronchitis, and their incidence could decrease in the future.

Biochemical relapse after radical prostatectomy is not exceptional, ranging from 10 to 40% in the literature. To prevent this biochemical failure, adjuvant radiotherapy was proposed to patients with a high risk of relapse. No phase III trial has actually validated this attitude. Best indications for adjuvant irradiation seem to be patients with an extensive extracapsular extension or multiple positive margins. Historical comparisons seems to confer, in these case, a benefit in biochemical control for adjuvant irradiation versus observation. Others authors prefer immediate post-operative irradiation, a delayed treatment, when biochemical relapse has occurred. This attitude has spared some patients irradiation useless. This salvage irradiation lowered the PSA level in 40 to 70% of the cases, but long-term efficiency is obtained only in the case of a low value of the PSA before irradiation. Delayed radiotherapy is, therefore, justified only if a close follow-up is performed, with repeated dosage of PSA. Whatever the case, it is important to differentiate between local and distant relapse: patients with positive nodes at the time of surgery are most likely at risk of distant relapse. It seems that patients with seminal vesicles involvement are also at high risk for distant relapse, but this must be confirmed.

L’interet du complement de dose apres radiotherapie externe (RTE) a ete demontre chez la plupart des patients. Nous rapportons notre experience de la curietherapie a haut debit de dose dans cette indication.

Purpose: To evaluate tolerance and efficiency of a boost dose delivered by high-dose-rate brachytherapy (HDRB) in conservative treatment of breast cancer. To evaluate the feasibility of brachytherapy on an out-patient basis. Methods: One hundred and six patients with T1–T2, N0–N1 breast cancers (108 breasts) have been treated with lumpectomy, external irradiation (45 Gy in 5 weeks), and a boost dose on the tumor bed with HDR iridium brachytherapy. Two fractions of 5 Gy were delivered 6 or 24 hours apart. Implantation was done during the lumpectomy (group A: 24 cases) or 3 to 4 weeks after the end of external irradiation (group B: 84 cases). For group B, the application was performed on local anesthesia, and did not require hospitalization. Characteristics of the population were as follows: T1: 77 (71.3%); T2: 31 (28.7%); median tumor size: 1.5 cm; histology: intraductal carcinomas (DCIS): 14 (13%); infiltrative ductal carcinomas (IDC): 84 (77.8%); others: 10 (9.2%). For IDC, surgical margins were found positive in 15 cases, and an extensive intraductal component was present in 22 cases. Results: All ambulatory HDR implants were performed as planned. No immediate toxicity was noticed, except 5 local hematomas. With a median follow-up of 45 months, 5 local relapses were observed (5-year local relapse rate: 5.1%). Only histological grade III was significantly correlated with local relapse. The 5-year disease-free survival and overall survival were respectively 93.8% and 93.3%. Cosmetic result was evaluated in 87 cases, and was good or excellent in 48 cases (63.2%), acceptable in 27 cases, and poor in 5 cases. Conclusion: HDRB allows the boost dose to be performed on an out-patient basis. It seems to offer the same local control as other boost techniques for localized breast cancer with acceptable cosmetic results.

Concomitant use of radiation therapy and chemotherapy is increasing steadily in the treatment of locally-advanced epithelial tumors. This approach has been proved effective in head and neck, esophageal, and canal and nonsmall-cell lung cancers. One of the best radiation sensitizers known to date is 5FU. In vitro cell model have demonstrated the importance of continuous exposure to the drug during 12 to 24 hours after the radiation session. These biological data have been confirmed by a randomized study in rectal cancer comparing 5FU bolus therapy versus 5FU given continuously during irradiation. Disease-free survival and overall survival were longer in the continuous infusion group. Cisplatin is being increasingly used in moderate but repeated doses, a regimen that requires central venous access. Similarly, etoposide, whose venotoxicity is well known, is an excellent radiation sensitizer that is gaining ground, most notably in the treatment of lung cancer. Nutritional support is a key component of all radiochemotherapy regimens used to treat digestive tract cancers and usually requires parenteral nutrition via a central venous access.

Purpose: To determine the predictive factors associated with hemoptysis and radiation bronchitis after endobronchial brachytherapy by univariate and multivariate analyses Methods and Materials: One hundred forty-nine patients underwent endobronchial brachytherapy and were divided into three therapeutic groups: group 1: patients treated with palliative intent ( n = 47); group 2: patients treated with curative intent (small endobronchial tumors without mediastinal or general dissemination: n = 73); group 3: patients also receiving external irradiation ( n = 29). One hundred twelve patients had previously received external irradiation. Brachytherapy was delivered with a dose per fraction ranging from 4 to 7 Gy and a prescription point between 0.5 and 1.5 cm, usually 1 cm from the source center. Two to six fractions were delivered according to the therapeutic group and clinical situation. The influence of the following variables on the incidence of hemoptysis or radiation bronchitis was studied: age, sex, Karnofsky score, therapeutic group, histologic type, endoscopic tumor length, dose per fraction, total brachytherapy dose, total external beam irradiation dose, total dose (brachytherapy dose plus external irradiation dose), volumes of the 100% and 200% isodoses, and volumes of the 7 and 14 Gy isodoses. Results: We observed 11 hemoptyses (7.4%), 10 were lethal. All but one occurred in patients with progressive disease. Two clinical factors were significantly associated with hemoptysis by univariate analysis: palliative group ( p = 0.009) and endobronchial tumor length ( p = 0.004). No technical factors seem to be implicated in the occurrence of hemoptysis. Only endobronchial tumor length remained in the multivariate model ( p = 0.02). Radiation bronchitis was observed in 13 cases (8.7%). By univariate analysis, a good Karnofsky score ( p = 0.02), curative treatment ( p = 0.02), and tumor location on trachea and main stem bronchus ( p = 0.002) were significantly associated with this complication. Two technical factors were also incriminated: the total dose ( p = 0.04) and the 100% isodose volume ( p = 0.02). By multivariate analysis, only the tumor location retained statistical significance ( p = 0.009). Conclusion: Hemoptysis is most likely due to disease progression, with the bleeding being facilitated by brachytherapy. Some rare cases could be a direct complication of brachytherapy itself, particularly when tumors are located in the upper lobes. In contrast, radiation bronchitis occurred more frequently in patients with controlled disease, and was significantly influenced by tumor location and technical factors (dose and volumes treated). Technical improvements should increase the therapeutic ratio.

Endobronchial tumour obstruction threatens to occur in cases of carcinoma of the bronchus throughout the course of the disease. Such patients can benefit from relief of the bronchial obstruction by several techniques which are currently available. We have treated 149 patients with endobronchial radiotherapy. Seventy three patients were treated with a view to cure, 47 with a palliative dose and 29 received endobronchial radiation in complement with external irradiation. The treatment was carried out in series repeated every 15 days until a maximum of three treatments, consisting of two sessions at 24 hour intervals delivering at each session and irradiating of 7 Gy with a 1 cm catheter. All the clinical signs were relieved and in 79% of patients there was a symptomatic benefit. One hundred and thirty two patients were evaluated by control endoscopy two months after the treatment and 64 had a complete histological remission. The median survival was 14.4 months for patients treated with intent to cure. Obtaining a histological remission was a gauge for prolonged survival (median survival 26.5 months), 11 (7.4%) had massive hemoptysis and 13 (8%) irradiation pneumonitis, all of which occurred some time after the therapeutic procedure. The results confirm the feasibility and the good results of endobronchial irradiation in this field and encourage the idea of controlled multi-centre trials in order to assess a placed of endobronchial radiotherapy in the therapeutic strategy of bronchial cancer.

As locally advanced and inoperable non-small cell lung cancers still have a poor prognosis, the present phase II study focused on the administration of concomitant chemotherapy and radiotherapy and was aimed at increasing both local and metastatic controls.Thirty-nine patients (36 male and three female patients, mean age, 56 years) were included into the study. Ninety five percent of them had a good performance status (OMS status 0 or 1). The histopathological analysis showed the existence of squamous cell in 64% of the cases. There was one stage I tumor, nine stage IIIA tumors and 24 stage IIIB tumors. In two cases, the tumor stage was unknown. The duration of each cycle of the protocol was 3 weeks and included the administration of cisplatin (50 mg/m2 at d1 and d2) and fluorouracil (5-FU) (1 gr/m2 in continuous infusion at d1, d2, and d3), and external beam irradiation (20 Gy subdivided into 2 Gy-fractions that were administered from d1 to d12); the 3rd week was a resting period.The tolerance to the treatment was good. Fifteen per cent grade 3-4 leucopenia, 3% grade 3-4 thrombopenia and 15% grade 3-4 nausea with vomiting were observed. No serious esophagitis was recorded. Chemotherapy was completed in more than 90% of the cycles. An objective response was described in 56% of the cases, with only 3% of complete responses. However, evaluation was done on average 6 weeks after radiotherapy, at a time where post-irradiation fibrosis could hamper radiological assessment. Median survival and 2- and 3-year survivals were 11.4 months, 27% and 14%, respectively. The only significant prognostic factor was the OMS performance status index, while the radiological response was particularly non-predictive of survival. Failure patterns were analyzed in 20 patients and consisted of the following: local relapse only, six cases; metastatic relapse only, 13 cases; both local and metastatic relapse, one case.The concomitant administration of 5-FU, cisplatin and external irradiation seems feasible in current clinical practice. Survival but not radiological response should be the only criteria to evaluate this type of association. Improvement in local control is not unlikely with this type of association.

During the evolution of lung cancer, bronchial obstruction is often noticed and is sometimes responsible for serious symptoms. Several methods of desobstruction can be proposed, including brachytherapy.One hundred forty-nine patients presenting with endobronchial brachytherapy were included into the study. Seventy-three were treated with curative intent, 47 with palliative intent and 29 with a combination of external irradiation and brachytherapy. We usually delivered a series of two 7-Gy fractions (1 cm from the catheter), the treatment being repeated one, two or three times.When all symptoms were taken into account, respiratory function improvement was present in 79% of the patients. Among the 132 tumors that could be evaluated via a new endoscopy 2 months after treatment, 64 (48.5%) were in complete histological remission. The median survival was 14.4 months for the patients treated with curative intent. Eleven massive hemoptysies and 13 radiation bronchitis were observed.These results confirm the feasibility and good results related to endobronchial brachytherapy, though controlled studies are needed to better define its place in the therapeutic strategy of bronchial carcinomas.

From January 1988 to July 1992, 68 patients presenting with a locally advanced and unresectable carcinoma of the head and neck region were given 3 to 5 courses of chemotherapy (5-FU 1 g/m2, day 1 to 3, cisplatin 4 mg/m2, day 1 and 2, 15 mg/m2 day 8) combined with simultaneous radiotherapy. Patients were enrolled in two protocols. In the initial one a 70 Gy total dose was delivered in 105 days, and in the latter the same dose was given in only 63 days. Toxicity was moderate and acceptable. In the 62 evaluable patients, a complete response was observed in 62%, and partial response in 24%. The complete response rate was higher (80%) in the population enrolled in the second protocol. Overall the median survival is 18 months. At 2 and 3 years, the overall survival is 48% and 30% respectively. These results suggest an influence of overall treatment duration on complete response rate and survival.

Combination of radiotherapy and chemotherapy (CRC) is actually one important way of research in oncology. Theoretical advantages are: 1) Spatial cooperation; 2) Additivity, which is only obtained if the toxicity of each modality are different; 3) Supra-additivity, which needs a rigorous in vitro definition; the only way to prove it is to make an isobologram analysis. This model has however, some limitations: qualitative variable could not be used, results could be different, depending on the cell line and isoeffect chosen... In fact, a supra-additivity was only demonstrated for cisplatinum and etoposide. Interactions mechanisms were: 1) at the molecular level, creation of new lesions or inhibition of radiation lesions repair; 2) At the cellular level, either cytokinetic cooperation with S-phase dependent drugs, or synchronisation for the drugs which blocked the cells in M-phase; 3) At the tissular level, reoxygenation, cycle redistribution... In clinical practice, three mains schedules have been described: sequential, alternating and concomitant. Only the latter try to use the supra-additivity phenomena. Aims of CRC could be: improvement or in survival or in local control, preservation of an functional organ... Depending on the tumor site and aim of the CRC, some schedules had to be preferred. For head and neck cancers, alternating or concomitant schedules offer a better local control. In bronchial carcinomas, sequential administration of the two modalities reduce the metastatic rate, but not the local control. Concomitant schedule improve the local control rate only. In some conservative protocol of bladder cancers, sequential and concomitant administration were used. In conclusion, CRC begins to be the usual clinical practice. The present schedules could be improved with the help of laboratory findings, which are now more and more precise.

Study objective To show that prolonged survival can be observed after high-dose rate (HDR) endobronchial brachytherapy as the sole treatment for some selected patients presenting with an endobronchial malignant obstruction. Patients Twenty-nine patients (group 1) who presented with an endoluminal localized tumor without metastatic extension were treated by HDR endobronchial brachytherapy and are compared with 22 subjects who presented with extraluminal dissemination and were palliatively treated (group 2). Treatment protocol Treatment consisted of sessions of two exposures, delivering 7 Grays at a 10-mm radius from the center of the applicator each, and repeated every 15 days, to a maximum of six exposures. Endoscopic response and survival are the main criteria of assessment. Results Follow-up bronchoscopies, performed 2 months after the end of the procedure, showed tumor regressions: macroscopic complete responses (CR) were observed in 21 of 25 patients evaluable in group 1, and 6 of 22 in group 2, with histologic CR in 18 and 2 patients, respectively. Median overall survival was not reached in group 1 after 23 months of follow-up; it was 5 months for group 2. Conclusions These results confirm that HDR brachytherapy can be used as a monotherapy for carefully selected patients who have small tumors to all appearances limited to the bronchial lumen and bronchial wall without adjacent parenchymal extension or metastatic disease.

For locally advanced, unresectable head and neck cancers, radiotherapy (RT) is the standard treatment but has poor results (25 % five year survival). Randomized trials showing improved survival in patients treated by concomitant chemoradiotherapy have been published for 5-FU, 5-FU-CDDP and Bleomycin [1, 2]. CDDP with 5-FU is a synergistic regimen against recurent and disseminated squamous cell carcinomas of the head and neck [3, 4]. To emphasize these results, we have attempted to increase the efficacy of RT with a concomitant and simultaneous Cisplatin (CDDP) and 5-Fluorouracil (5-FU) chemotherapy (protocol PURE).