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I cancri della parete posteriore della faringe sono dei tumori rari, tra i quali l’istologia preminente e il carcinoma epidermoide. Essi hanno origine, il piu delle volte, alla giunzione oro-ipo-faringea. Il loro trattamento e ancora discusso, nella misura in cui sono progredite parallelamente le tecniche di radioterapia, le associazioni radioterapia-chemioterapia e le tecniche chirurgiche (chirurgia ripartiva che permette di ipotizzare delle exeresi estensive migliorando il controllo locale). Il trattamento e basato, il piu delle volte, su un’associazione chirurgia-radioterapia postoperatoria, tenuto conto dell’aggressivita locale di queste lesioni. La loro prognosi rimane, tuttavia, piuttosto infausta a causa di uno stadio spesso avanzato al momento della diagnosi e del terreno fragilizzato su cui essi insorgono.

Los canceres de la pared posterior de la faringe son tumores infrecuentes, entre los que la histologia predominante es el carcinoma epidermoide. En la mayoria de los casos, se originan en la union orohipofaringea. Su tratamiento aun es motivo de debate, debido a la evolucion paralela de las tecnicas de radioterapia, las asociaciones de radioquimioterapia y las tecnicas quirurgicas (cirugia reparadora que permite plantear resecciones extensas con un mejor control local). El tratamiento se basa en la mayoria de las ocasiones en una asociacion de cirugia y radioterapia postoperatoria, debido a la agresividad local de estas lesiones. Sin embargo, su pronostico sigue siendo bastante sombrio, debido a que se suelen diagnosticar en un estadio avanzado y a que aparecen en pacientes debilitados.

Purpose: Conservative treatment of soft tissue sarcomas most often implies combination of surgical resection and irradiation. The aim of this study was to evaluate low-dose-rate intraoperative brachytherapy, delivered as a boost, in the local control of primary tumors, with special concern about treatment complications. Methods and Materials: Between 1986 and 1995, 112 patients underwent intraoperative implant. This report focuses on the group of 58 patients with primary sarcomas treated by combination of conservative surgery, intraoperative brachytherapy, and external irradiation. Most of the tumors were located in the lower limbs (46/58—79%). Median size of the tumor was 10 cm, most of the lesions being T2–T3 (51/58—88%), Grade 2 or 3 (48/58—83%). The mean brachytherapy dose was 20 Gy and external beam irradiation dose 45 Gy. In 36/58 cases, iridium wires had to be placed on contact with neurovascular structures. Results: With a median follow-up of 54 months, the 5-year actuarial survival was 64.9%, with a 5-year actuarial local control of 89%. Of the 6 patients with local relapse, 3 were salvaged. Acute side effects, essentially wound healing problems, occurred in 20/58 patients, late side effects in 16/58 patients (7 neuropathies G2 to G4). No amputation was required. The only significant factor correlated with early side effects was the location of the tumor in the lower limb ( p = 0.003), and with late side effects the vicinity of the tumor with neurovascular structures ( p = 0.009). Conclusion: Brachytherapy allows early delivery of a boost dose in a reduced volume of tissue, precisely mapped by the intraoperative procedure. Combined with external beam irradiation, it is a safe and efficient treatment technique leading to high local control rates and limited functional impairment.

Resume L'association chirurgie-radiotherapie postoperatoire est le traitement de reference de nombreux cancers des voies aerodigestives superieures. Les echecs de ce traitement sont surtout, mais non exclusivement, locoregionaux. Les parametres histologiques permettent d'identifier les tumeurs a haut risque de rechute. La revue des donnees disponibles indique que la chimiotherapie, delivree de facon concomitante a la radiotherapie, est susceptible d'ameliorer le controle locoregional chez ces patients. Cela devra etre confirme par les essais en cours, de meme que l'eventuelle efficacite d'une polychimiotherapie sur la prevention du risque metastatique.

Purpose: To determine the effect of low-dose splenic irradiation on severe Zidovudine-resistant, HIV-1–associated thrombocytopenia (HAT). Methods and Materials: Between September 1994 and October 1996, 17 patients were included in a prospective study. The patients met the following criteria for inclusion: hemorrhagic symptoms or a platelet count below or equal to 50 × 10 9 /l and normal numbers of megakaryocytes on bone aspiration. The mean baseline platelet count was 20.3 (± 14.4) × 10 9 /l; four patients had a platelet count inferior to 10 × 10 9 /l. Splenic volume was defined by ultrasonography. A total dose of 9 Gy was given using an isocentric parallel pair field technique. Results: One month after the end of treatment six patients had a significant rise in their platelet count. Clinically, hemorrhagic symptoms stopped for all patients that were symptomatic. Unfortunately, duration of response was short because for one patient only the platelet count remains stable with a follow-up of 6 months. All patients are alive and in recent evaluation, with four out of eight patients receiving a combination of antiretroviral therapy had a platelet count above 50 × 10 9 /l. Conclusion: Our results are disappointing concerning the duration of response, especially comparatively to those reported in autoimmune thrombocytopenia. Mechanisms of HAT are more complex, and megakaryocytes' infection may play an important role. Splenic irradiation should be considered as palliative treatment for the minority of patients with severe bleeding that does not respond to standard medical treatment.

Technical evolution of stereotactic irradiation: fractionated doses. The development of non-invasive head fixation systems, allowing 3D determination of the target coordinates, has lead to the increased use of fractionated stereotactic irradiation. These systems have been checked for accuracy and the mean precision of repositioning has been evaluated to ± 1 mm. With the mean geometrical accuracy set at ± 1 mm, a 2 mm safety margin is usually added to the clinical target volume in order to define the planning target volume. Quality assurance procedures must conform to the required precision of the technique while remaining realistic in day-to-day use relative to planned conventional treatments. Biologically different from single dose irradiation, the fractionated stereotactic irradiation completes the range of techniques used in the treatment of intra-cerebral lesions.

Resume Le developpement actuel de techniques complexes d'irradiation therapeutique visant toutes a une adequation maximale entre le volume tumoral et celui recevant la dose prescrite pose le probleme des elements objectifs de justification de ces demarches multiples. Au-dela de l'amelioration eventuelle de la performance antitumorale, il est logique de rechercher dans la reduction du risque de complications une des raisons de ces avancees techniques. Les donnees actuelles de la litterature ne permettent pas d'etayer immediatement cette hypothese, mais sont cependant suffisantes pour orienter la recherche clinique necessaire. Dans ce cadre, il est propose l'application de methodes d'aide a la decision fondees sur la simulation probabilistique des differents evenements medicaux suivant une prise en charge radiotherapique initiale. L'analyse de la valorisation de ces evenements, et en particulier des complications, permet de penser que des etudes de type cout/benefice sont susceptibles de repondre a la question posee, a la condition expresse de concentrer l'etude sur des maladies et des techniques soigneusement selectionnees. La necessite de realiser des etudes cliniques prospectives de ce type parait etre d'une evidente actualite.

Resume But de l'etude Les auteurs presentent une evaluation comparant la valorisation financiere en lettres clefs Z de l'activite radiotherapique annuelle d'un centre de lutte contre le cancer et le montant des charges directes reellement mises en jeu pour la realisation de cette activite. Materiels et methodes Les charges directes ont ete calculees en cumulant leurs differentes composantes, en particulier les salaires des personnels dont le montant a ete etabli pour chaque acte et par categorie de personnel, au prorata du temps de travail effectivement consacre. Resultats La comparaison entre charges directes et montant total des actes codes Z conduit a plusieurs resultats: - l'ordre de grandeur des sommes engagees est voisin dans les deux modes de calcul; - cette apparente concordance recouvre en fait de tres gros ecarts lors d'une analyse par acte therapeutique; - le montant de la valorisation des lettres clefs est d'autant plus inferieur a celui des charges reelles correspondantes que l'acte therapeutique etudie s'eloigne des techniques qualifiees de ≪ standardisees ≫; - les differences constatees ne concernent pas de facon homogene tous les elements constitutifs de la cotation des actes radiotherapiques; en particulier, il apparait que les etapes medicales, de preparation et d'etude physique sont regulierement sous-cotees alors que l'irradiation proprement dite est souvent surcotee, son mode de valorisation etant par ailleurs devenu discutable. Conclusion A la vue des resultats de cette analyse comparative, les auteurs proposent des modifications des objectifs generaux et du contenu pratique de la nomenclature des actes de radiotherapie et de curietherapie.

Resume But de l'etude Entre novembre 1988 et mai 1992, 14 patients ont participe a une etude pilote dans le but d'evaluer la faisabilite d'une reirradiation hyperfractionnee sur des recidives ou des seconds cancers developpes en volume irradie. Materiel et methodes Chaque patient inclus dans l'etude avait fait l'objet d'une intervention chirurgicale et, en raison de marges envahies et/ou d'adenopathies en rupture capsulaire, une reirradiation leur a ete proposee au cours de laquelle une dose de 60 Cy a ete delivree en 5 semaines a raison de deux seances quotidiennes de 1,2 Gy espacees d'au moins 6 heures. Resultats Sur les 14 patients, dix ont termine leur irradiation. Tous les patients ont eu une reaction muqueuse ne necessitant pas d'interruption de la radiotherapie. Dix patients sont decedes entre 3 et 41 mois apres la fin de la reirradiation (moyenne: 14 mois), trois etaient en remission clinique complete au moment de l'analyse, soit 48 et 71 mois apres la reirradiation, et un patient etait vivant 74 mois apres la reirradiation mais avec une poursuite evolutive. Le taux de controle local en volume irradie etait de 43 %. Les taux de survie globale a 2 et 3 ans etaient respectivement de 50 et 35 %. Treize complications tardives ont ete observees: quatre de grade 1, sept de grade 2 et deux de grade 3. Chez trois patients (ceux vivants lors du recueil des donnees) ont pu etre realises des histogrammes dose-volume et ainsi determineees les doses cumulees des deux irradiations. Conclusion En depit de resultats carcinologiques mediocres, il est possible de delivrer 60 Cy selon un schema hyperfractionne sans crainte de complications rhedibitoires.

Purpose: To report the final results of a prospective randomized trial that aimed to evaluate efficacy and toxicity of concomitant postoperative radiotherapy and Cisplatin infusion in patients with Stage III or IV squamous cell carcinoma of the head and neck histological evidence of extracapsular spread of tumor in lymph node metastases(s). Methods and Materials: Radiotherapy was delivered using a daily dose of 1.7 Gy for the first 54 Gy and 1.8 to 2 Gy until the completion of the treatment. Cisplatin 50 mg i.v. with forced hydratation was given or not every week (i.e., seven to nine cycles) concurrently with radiotherapy. A total of 44 patients were treated by irradiation only (RT group) and 39 by irradiation with chemotherapy (CM group). Results: The RT group displayed a higher rate of loco-regional failures as compared to CM group (41 vs. 23%; p = 0.08). The overall survival, the survival corrected for deaths by intercurrent disease, and the disease-free survival were better in CM group as compared to RT group with statistically significant differences. Survival without loco-regional treatment failure was better in the CM group, the difference being close to the level of significance ( p = 0.05). Survival without distant metastases were comparable in the two therapeutic groups. Ten severe late complications were observed, four in the RT group (17%) and six in the CM group (22%). Cox univariate analysis comfirned the importance of the therapeutic modality in predicting the overall surviva, the survival corrected for deaths by intercurrent disease, and the disease-free survival. Conclusions: The present final report of this phase III study confirms preliminary results. The concomitant use of 50 mg weekly Cisplatin infusion and postoperative radiation improved loc-regional control and survival. No significant increase of laet radiation complications was observed in the CM group.

Resume Les auteurs presentent une analyse retrospective des couts financiers reels engages lors de la realisation des actes therapeutiques realises dans le departement de radiotherapie du centre Claudius-Regaud. Cette evaluation a ete realisee a partir d'un releve precis des differents constituants valorisables des actes de traitement, en particulier pour ce qui concerne la part salariale qui a fait l'objet de mesures iteratives du temps consacre a chaque acte par les differentes categories de personnel concernees. Les resultats montrent une tres grande diversite du cout reel des differents actes et en particulier de ceux qui relevent d'une demarche prospective de recherche clinique qui sont en regle les plus onereux. Il apparait possible de disposer ainsi d'un instrument d'orientation et de choix strategique lors de la modification ou de l'innovation therapeutique dans le cadre du fonctionnement d'un service hospitalier a valence universitaire. La congruence de ces resultats avec la nomenclature des actes medicaux et le systeme d'allocation globale annuelle de ressources est discutee.

From 1977 to 1990, 94 evaluable patients were treated with iridium-192 implantation in the Centre Claudius Regaud for a Stage I (52 patients) or a Stage 11(42 patients) squamous cell carcinoma of the mobile tongue and/or the floor of the mouth. Interstitial brachytherapy was associated with external irradiation in 68 patients (group 1; mean dose, 48 Gy for external irradiation, 26 Gy for brachytherapy) or was exclusive in 26 patients (group 2; mean dose, 66 Gy). The mean follow-up was 44 months. Eleven acute complications were noted during or immediately after the implant (1 lethal myocardial infarction, 6 hematomas of the tongue which spontaneously resolved, 3 local sepsis). The mean duration of the mucositis was 9 weeks (from 4 to 20 weeks). Ten patients (17%) experienced a late complication (8 in group 1, 2 in group 2): 3 bone necroses requiring hemimandibulectomy (1 post-operative death), 1 tongue necrosis treated by a transoral mucosal excision, 6 bone expositions which recovered after medical treatment. Local control rates for T1 and T2 tumors were 75% (39/52) and 51% (21/41), respectively. Sixteen patients (17%) presented a nodal relapse which was associated in 6 cases with a concomitant local relapse. The local control rate of T1 tumors was 64% (23/36) in group 1 versus 100% (16/16) in group 2 ( p p > 0.3). The influence of 13 parameters on the local control was studied in analysis. In the one model analysis, a cox regression tumor size was significantly predictive of actuarial local recurrence ( p p = 0.06). The other variables (age, sex, anatomic site, macroscopic aspect of the tumor, pathologic differentiation, technique of implant, intersource spacing and dose rate) had no significant influence. This retrospective study suggests that exclusive brachytherapy is the best modality in terms of local control and functional results.

In this paper, we describe the effect of the inhibitor of farnesyltransferase (FTI-277) on radioresistance induced by the 24-kDa isoform of FGF2 in human cells expressing wild-type RAS. Treatment with FTI-277 (20 μM) for 48 h prior to irradiation led to a significant decrease in survival of radioresistant cells expressing the 24-kDa isoform (HeLa 3A) but had no effect on the survival of control cells (HeLa PINA). The radiosensitizing effect of FTI-277 is accompanied by a stimulation of postmitotic cell death in HeLa 3A cells and by a reduction in ${\rm G}_{2}/{\rm M}\text{-phase}$ arrest in both cell types. These results clearly demonstrate that at least one farnesylated protein is involved in the regulation of the radioresistance induced by the 24-kDa isoform of FGF2. Furthermore, the radiation-induced ${\rm G}_{2}/{\rm M}\text{-phase}$ arrest is also under the control of farnesylated protein. This work also demonstrates that FTase inhibitors may be effective radiosensitizers of certain human tumors with...

To measure the incidence of second non-germ cell malignancies (SNGCM) in patients treated for a stage I-II testicular seminoma.From 1970 to 1992, 131 evaluable patients received in the Institut Claudius Regaud a post-orchiectomy treatment for a stage I-II testicular seminoma. The therapeutic modalities, including salvage treatment for six recurrences, were as follows: infradiaphragmatic radiotherapy (IDRT) (n = 55); infra- and supradiaphragmatic radiotherapy (IDRT + SDRT) (n = 64); IDRT + SDRT with chemotherapy (n = 12). The mean follow-up was 11 years. The cumulative incidence of SNGCM was compared to the overall cancer incidence in the general male population on the basis of the Tarn Cancer Registry; the relative risk was expressed as a standardized incidence ratio (SIR).Overall, the cumulative incidence of SNGCM was 10.7% (14/131 cases). The SIR was equal to 2.81 (95% confidence interval (CI) 1.54-4.72; P0.001) and increased with follow-up duration. The SIR was significantly increased in 64 patients treated with IDRT + SDRT (SIR = 3.08; 95% CI 1.47-5.66; P = 0.002) but not in 55 patients treated with IDRT alone (SIR = 0.62; 95% CI 0.01-3.43; P = 0.8). The 12 patients who received chemotherapy had an SIR of 26.2 (95% CI 5.48-77.69; P0.001), while the SIR was 2.26 in the 119 patients who did not receive any chemotherapy (95% CI 1.13-4.04; P = 0.01 ). Of four hematologic malignancies, three appeared in the 12 patients who received chemotherapy.An increased risk of SNGCM after SDRT + IDRT has been demonstrated. After IDRT alone, the risk of second cancer is not incremented after a median follow-up of 6 years, but further observation of the patients is necessary to achieve final conclusions. Our results suggest that the risk of second cancer and especially of hematologic malignancy is increased by the association of chemotherapy and radiation.

The development of non-invasive head fixation systems, allowing 3D determination of the target coordinates, has lead to the increased use of fractionated stereotactic irradiation. These systems have been checked for accuracy and the mean precision of repositioning has been evaluated to +/- 1 mm. With the mean geometrical accuracy set at +/- 1 mm, a 2 mm safety margin is usually added to the clinical target volume in order to define the planning target volume. Quality assurance procedures must conform to the required precision of the technique while remaining realistic in day-to-day use relative to planned conventional treatments. Biologically different from single dose irradiation, the fractionated stereotactic irradiation completes the range of techniques used in the treatment of intra-cerebral lesions.

Squamous cell carcinomas of the oral cavity were treated in 157 patients by surgery as first-line (104) or salvage (53) treatment. Postoperative irradiation delivered either for locally advanced tumors (stade III-IV) or for unfavorable histological data (nodal or surgical margins involvement). The retrospective study with a mean time of follow-up of 2.5 years shows a loco-regional control rate of 75% statistically influenced by histological nodal status (p0.01). Cumulative and cause specific survival rates at 5 years are 41.1% and 57.2% respectively. T stage was found to be a prognostic factor of survival (p0.01) as bone involvement (p0.05). Surgical margins are influent on local control and survival only in absence of radiation.

The basic fibroblast growth factor-(bFGF) mediated signal transduction pathway has been implicated in cellular resistance to ionizing radiation. bFGF is synthesized from the same mRNA in four isoforms resulting from alternative initiations of translation at three CUG start codons (24, 21.5, and 21 kDa) and one AUG start codon (18 kDa). We analyzed the implication of high- and low-molecular forms of bFGF in radioresistance acquisition. For this, we transfected HeLa cells with retroviral vector containing either the CUG-initiated 24-kDa molecular form (HeLa 3A cells), the AUG-initiated 18-kDa molecular bFGF form (HeLa 5A cells), or the vector alone (HeLa PINA cells). A significantly increased radioresistance was obtained only in HeLa 3A cells (Dq = 810 +/- 24 cGy) compared with wild-type cells (Dq = 253 +/- 49 cGy) or HeLa PINA cells (Dq = 256 +/- 29 cGy; P0.001). This radioprotective effect was independent of an inhibition of radiation-induced apoptosis but related to an increased G2 duration after irradiation and to an hyperphosphorylation of p34cdc2 kinase. Knowledge of the high-molecular bFGF form-induced radioresistance pathway could offer novel targets for decreasing the radioresistance phenotype of tumors expressing high amounts of bFGF, such as glioblastoma.

A phase I-II study was initiated in February 1991 of concomitant radiation and cisplatin (CDDP) in the treatment of unresectable head and neck squamous cell carcinomas (n = 12). The first patient was treated palliatively for a cervical recurrence of laryngeal cancer. The 11 other patients had locally advanced (stage IV) previously untreated carcinomas of the oropharynx (n = 9), hypopharynx (n = 1), or cervical node with unknown primary site (n = 1). Standard external radiation was carried out up to a total dose of 60 Gy/6 weeks (7 MeV electron beam) for the first patient and 72 Gy/8 weeks (Co 60 beam) for the other 11 patients. CDDP was infused continuously during the entire radiation treatment, 5 days/week. The starting dose was 4 mg/m 2 /day and was escalated by increments of 1 mg/m 2 /day; dose-limiting toxicity was observed at 7 mg/m 2 /day. Neutropenia (grade 4, one patient; grade 3, three patients) and thrombocytopenia (grade 3, one patient; grade 2, one patient) were the limiting factors. Therefore, the recommended dose of CDDP is 6 mg/m 2 /day. All patients but one completed the scheduled radiation. For the entire group, mucositis was not more severe than that observed with radiotherapy alone. There was no nephro-, oto-, or neurotoxicity. A complete response was obtained in eight (66%) patients. Ofthese, four were free of disease 12-34 months after completion of treatment and one had a total glossectomy for a tongue necrosis. For the whole series, the mean overall survival was 16 months posttreatment. Pharmacokinetic analysis indicated the total cisplatin accumulation at the end of treatment to be 743-1551 ng/ml. Accumulation of ultrafilterable platin was noted in only one patient (137 ng/ml at the end of treatment).

At the present time, the current improvement of technical and dosimetric aspects of radiation oncology has to be evaluated in terms of potential benefit for the patient and the society. For this last point of view, specially designed economic analyses must be performed in order to justify the number of resources involved by these technical improvements. If the question is how the current technical procedures could reduce the risk of undesirable side-effects, the response cannot be immediately drawn from the literature. This paper emphasizes the possibility to evaluate the role of side-effects as endpoints of economic analyses when using special models in medical decision making such as Markov's. Only few oncologic situations are reliable to properly analyze the relationship between sophisticated radiation techniques and the incidence of post-radiation complications. These situations should be selected when prospective economic analyses are planned in the field of radiation therapy.

Financial costs from "Z" procedures were evaluated and compared with the amount of direct costs that are needed for the annual activity of a radiation oncology department.The various components, particularly staff earnings that are estimated for each procedure according to their category and working time, were cumulated for calculation of direct loads.Comparisons between direct expenses and the total amount of Z procedures led to the following results: the global cost is the same; at analysis of therapeutic procedures, however, this apparent similarity masks some very significant gaps; valorization of Z procedures is much lower than that of the corresponding real loads, especially when therapeutic procedures are quite different from techniques that are considered as "standard"; these differences do not apply to all the components of radiation therapy procedures. In particular, medical steps would be uniformly underestimated, while irradiation per se is overestimated.The authors suggest modifications of the general objectives and items of the nomenclature of radiotherapy and brachytherapy procedures.

Between November 1988 and May 1992, 14 patients were enrolled in a pilot study to evaluate the feasibility and results of hyperfractionated reirradiation for the treatment of head and neck recurrences or of second primary tumors developed in a previously irradiated volume.All patients underwent a surgical resection for the treatment of their recurrence or second cancer. Reirradiation was proposed because of positive margins and/or lymph node metastasis with extra-capsular spread. The planned reirradiation dose was 60 Gy over 5 weeks, with two daily fractions of 1.2 Gy delivered 6-8 hours apart.Of the 14 patients, 10 received the reirradiation scheduled dose (ie, 60 Gy). All patients experienced an acute mucositis that never led to disruption of the treatment. Ten patients died 3 to 41 months after reirradiation (mean: 14 months), three were disease-free 48 to 71 months after reirradiation and one was alive with local progressive disease 74 months after reirradiation. The overall local control rate within the reirradiated volume was 43%. The 24- and 36-month overall survival rates were 50 and 35%, respectively. Overall, 13 late complications were noted: four were grade 1, seven were grade 2, and two were grade 3. Three patients still alive in September 1993 and whose initial files were available were enrolled in an additional study to assess from dose-volume histograms the cumulative doses delivered by the two irradiations.Despite poor local control, reirradiation using a hyperfractionation schedule with high dose level is feasible in terms of acute and late toxicity.

We conducted a retrospective study of 34 patients treated by radical neck dissection followed by radiotherapy for one or several cervical adenopathies without a primary tumor. Mean follow-up was 48 months. During follow-up, 6 patients developed a presumed primary tumor, and 11 patients presented with recurrent lymph nodes. We found no statistically significant predictive factor, as to either clinical characteristics or the histological nature of the adenopathies. On the other hand, the number of metastatic lymph nodes found on the surgical specimen was correlated with the risk of lymph node recurrence. Among the prognostic factors with an unfavorable effect on survival, the dimensions of the adenopathy, its fixed characteristic and its TNM status, were identified. In this series, the appearance of a primary tumor did not seem to worsen the prognosis. On the other hand, the appearance of lymph node recurrence predicted poorer survival rates. The results are discussed and compared with those found in the literature.

Between November 1988 and May 1992, 19 patients were enrolled in a pilot study to evaluate feasibility and results of a hyperfractionated reirradiation in the treatment of head and neck recurrences or second primary tumors developed in previously irradiated volume. Patients were divided in two groups according to the initial treatment before reirradiation: group 1 included 14 patients treated with radical surgery and reirradiated because histological evidence of positive margins and/or extra capsular spread of tumor in lymph node metastases; group 2 included five patients treated with three cycles of CDDP-5FU for unresectable tumors and reirradiated because they experienced a complete or good partial (≥80%) response after chemotherapy. The reirradiation planned dose was 60 Gy in 5 weeks, with two daily fractions of 1.2 Gy spaced by 6–8 h intervals. Reirradiation was delivered exclusively with photon beams in 17 cases and with a combination of photon and electron beams in two cases. Follow-up ranged from 3 to 45 months with a median of 17 months. Of the 19 patients, 13 received the reirradiation scheduled dose of 60 Gy. For the six remaining patients, the reirradiation doses ranged from 45.6 to 57.6 Gy. All patients experienced an acute mucositis which never led to interruption of treatment. Of the 14 patients of group 1, 10 died 3–41 months after reirradiation (mean: 14 months), three were disease-free 16–37 months after reirradiation and one patient was alive with local progressive disease 39 months after the reirradiation. The overall local control within reirradiated volume was 36% before and 43% after salvage surgery. For all group 1 patients, 12- and 24-month overall survival was 64 and 36%, respectively (mean: 21 months). All patients of group 2 presented a local failure within the reirradiated volume. Three of them died 12, 16 and 25 months after reirradiation, while two of them were alive with progressive disease 25 and 30 months after reirradiation, respectively. The mean survival was 22 months. Overall, 15 late complications were noted: five grade 1, eight grade 2 and two grade 3. There was no lethal complication. Four patients alive in September 1993, and whose initial technical files were available, were enrolled in an additional study to assess the cumulative doses delivered by the two irradiations. Despite disappointing loco-regional control rates, a reirradiation of 60 Gy using a hyperfractionated schedule is feasible in terms of acute and late toxicity.

Palliative treatment of head and neck cancers needs an initial evaluation based upon clinical symptoms and tumoral behaviour. Local recurrences are the most frequent presentation of tumoral failures. The therapeutic management of these local recurrences requires a mixture of unspecific and specific oncologic procedures. Radiotherapy and chemotherapy are frequently used in those circumstances in order to reduce the tumoral volume and to facilitate the effectiveness of unspecific treatments. Management of metastatic disease is often impaired by the moderate efficiency of chemotherapy while this treatment leads to marked side effects. Basically, the best therapeutic choice depends on the expected positive balance between the improvement of symptoms and the level of treatment-related side effects. However, daily clinical approach is a better way to care these patients than predefined rigid protocols.

To increase geometric treatment accuracy in radiation therapy, we used a novel digitized method and original image processing. The radiographic films that are conventionally used for verifying each beam during the treatment were digitized by a Kodak digital system and then an original image enhancement was applied. For the evaluation of our technique, a clinical trial with two tests was used. The trial involved four readers doing 80 reading. The enhanced films were judged to be of higher quality than the non enhanced films (p = 0.001) and were read more accurately (por = 0.001). This automatic enhancement of digitized captured portal images can be easily integrated into the busy routine of a radiotherapy department.

The authors present a retrospective analysis dealing with the cost of therapeutic procedures achieved in the department of radiotherapy of the Centre Claudius-Regaud. This analysis was performed according to the actual cost of the different components of each treatment including the human costs. For this last purpose, serial countings of time spent by each category of employees were performed and then translated into financial terms. Results show a large discrepancy between the costs of therapeutic procedures. These differences are mainly related to the purpose of therapeutic plan, dealing with the most expensive procedures dealing with the developmental treatments. This study provides a tool that can be used by medical and/or administrative managers of radiation oncology departments when changes or innovations in therapeutic procedures. This cost accounting analysis is compared to the French administrative procedures used to pay the health care services and to determine the level of hospital resources.

Between May 1986 and June 1992, 48 patients with soft tissue sarcomas underwent 50 intraoperative interstitial implants in conjunction with conservative tumoral resections. Brachytherapy was part of the initial treatment in 27 cases and was done in 21 other previously treated patients. For the last ones brachytherapy was, in most of the cases, the only treatment in addition to surgery. The implant dose was 40–65 Gy. When combined with external irradiation the mean prescribed dose was 20 Gy (12–25 Gy). With a median follow-up of 33 months, the 3-year actuarial survival rate was 81% and the local disease-free survival 91.7%. Five local failures were observed only in patients with recurrent sarcomas: two were inside the treated volume and three outside (local failure 548=10.4%). Acute side-effects occurred in 11 patients (1148 = 23%), with skin breakdown (two cases) infection and hematoma (one case), infection, lymphocele, secondary skin breakdown and vascular rupture (one case), infection and limited skin breakdown (two cases) and delayed healing (five cases). As a consequence, six patients required reoperation but no amputation was necessary. The functional results were good. Only three patients had a moderate limitation of movement. Late complications occurred in five patients: bone fracture (one case), leg oedemas not interfering with normal activity (three cases), peripheral neuropathy fibrosis related requiring surgery (one case). Therefore, this preliminary report shows that adjuvant intraoperative brachytherapy is feasible and is safe in treating soft tissue sarcomas, even in previously irradiated patients. However, further evaluation is needed to determine the real place of intraoperative implant in the management of soft tissue sarcomas.

In order to enhance radiation effects in the treatment of unresectable Head and Neck squamous cell carcinoma, we initiated a phase I-II study in February 1991 with concomitant radiation and cisplatin in the treatment of resectable Head and Neck squamous cell carcinoma. The first patient was treated in a palliative intend for a cervical recurrence (cutaneous metastatic lymphangitis) of laryngeal cancer. The seven other patients had a Stage IV M0, previously untreated, oropharyngeal carcinoma. Standard external radiation was carried out up to a total dose of 60 Gy/6 weeks (7 MeV electron beam) for the 1st patient and 72 Gy/8 weeks (Co60 beam) for the 7 other patients. Cisplatin was given during the entire radiation treatment, by continuous infusion, 5 days a week, at doses of 4 mg/m2/d for the 1st patient, 5 mg/m2/d for the two following patients and 6 mg/m2/d for the last five patients. One patient with a poor initial performance status (three in the WHO scale) stopped his treatment on the 6th week due to a grade 3 mucositis with deglutition pneumonia. He died 2 months later with progressive carcinoma. For one other patient, treatment was discontinued for 1 week after 48 Gy, due to a grade 3 mucositis. The other patients completed the planned protocol without any interruption. Mucositis (grade 3 in two cases, grade 2 in four cases), dermitis (grade 3 in two cases, grade 2 in four cases) and neutropenia (grade 2 in two cases) were the most frequent acute toxicity. Of the seven patients treated with a curative intend, six are free of disease at 6 to 28 months after completion of treatment. A pharmacokinetic study showed a total platinum accumulation. The mean value at the end of treatment reached 1157 ng/ml. Only one patient experienced an accumulation of the ultrafilterable platinum (137 ng/ml at the end of treatment).

Duration of the G 2 -phase delay and arrest after exposure to ionizing radiation is thought to influence radiosensitivity. The kinase activity of the p34 cdc2 -cyclin B complex and the p34 cdc2 -cyclin A complex is implicated in G 2 - to M-phase transition and in G 2 -phase arrest after exposure to ionizing radiation. We analyzed the expression level and the subcellular location of p34 cdc2 , cyclin A and cyclin B in head and neck squamous cell carcinoma (SCC) tumors; samples were obtained from patients with locally nonrecurrent and recurrent tumors that had been treated by surgery and radiotherapy. No significant difference was noticed in cyclin A, cyclin B and p34 cdc2 expression. However, we noted a significant preferential cytoplasmic location of p34 cdc2 in recurring tumors compared to the nonrecurring ones (P < 0.001). This abnormal location of p34 cdc2 occurs even in primary tumors in patients with recurring tumors, suggesting that a default in the activation of p34 cdc2 kinase could be implicated in clinical radioresistance.