Search

Verification of absorbed dose in target volume is a key factor for quality assurance in radiotherapy. In vivo measurements allow evaluation of the variations in dose with time and variations between measured doses and calculated doses by TPS. The aim of this work were to evaluate reproducibility of patient positioning and to compare calculated doses by 2 different TPS.Twenty patients were divided in 2 groups according to the thickness of their breast (mean SSD = 92.9 cm). In vivo measurement was performed within the first two sessions.Reproducibility of SSD evaluation was made on 12 beams between 2 fractions. With a tolerance margin of 0.5 cm, positioning errors were present in 33% (4/12). The 2 TPS were in agreement in 75% (30/40).In vivo dosimetry can be a very interesting tool to assess patients positioning variations and TPS dose calculation.

Vascular reconstruction (bypasses or endoluminal procedures) is still associated with a significant rate of restenosis. For restenosis, smooth muscular cells are the principal actor by their property to migrate, proliferate and secrete extra-cellular substance after their change of phenotype. A variety of pharmacological and mechanical strategies have been directed with limited success. Using ionizing radiation have been recently developed, aiming to reduce the cell proliferation and consecutive restenosis following vessel injury (anastomoses or angioplasty). We reviewed the use of radiations on animals, cellular action and recent clinical trials. Recent clinical trials confirm an effective action of using radiations for restenosis prevention. We reviewed methods of delivering radiations also drawback and consequences using these hopefully methods.

Biological effectiveness of low LET radiations is dependent on the partial oxygen pressure in the tissues at the time of energy deposit. Direct pO2 measurements demonstrate a low oxygen tension in tumours compared with surrounding normal tissues. Tumour hypoxia mediates response to treatment (radiotherapy and chemical modifiers), and modulates gene expression and angiogenesis, a key factor for metastases. The knowledge of these microenvironmental factors will allow new treatment strategies.

Soft tissue sarcomas of the extremities are currently treated with more conservative and functional approaches, combining surgery, radiotherapy and chemotherapy. The role of external beam radiotherapy and brachytherapy has been defined through randomised studies performed in the 80's and 90's. However, the ubiquity of tumour location for these tumours makes difficult a systematic definition of local treatments. Tumour volume definition is based on pre and post surgical imaging (MRI) and on described pathological report. The clinical target volume will take into account quality of the resection and anatomical barriers and will be based on an anatomy and not only on safety margins around the tumour bed. General rules for this irradiation (doses, volumes) and principal results will be presented.

Soft tissue sarcoma accounts for a approximately 1% of all cancers. Excluding Kaposi sarcoma, the incidence of soft tissue sarcoma has remained stable in Europe (3-4/100,000). ENDOGENOUS FACTORS: Endogenous factors are related to rare genetic syndromes (Li-Fraumeni syndrome, neurofibromatosis, Werner syndrome, bilateral retinoblastom). EXOGENOUS FACTORS: Exogenous factors associated with soft tissue sarcoma are essentially iatrogenic: radiation therapy (prevalence of radiation-induced sarcoma: 0.17-0.21%) and chronically edematous arms after radical mastectomy for breast cancer (Stewart-Treves syndrome). Many studies suggest that environmental or occupational exposure to chlorophenol, phenoxy-herbicides or dioxin increase the risk of soft tissue sarcoma. FURTHER RESEARCH: Little is known about the epidemiology of soft tissue sarcoma. Case-control studies are needed.

Somatostatin receptor scintigraphy (SRS) may be of interest for staging Merkel Cell Carcinoma (MCC). This study was undertaken to evaluate the sensitivity and specificity of SRS and to determine its role compared to conventional investigations.From 1993 to December 2000, 20 patients (10 females and 10 males, aged from 38 to 88, mean 66 years) were included prospectively. At the time of SRS: 12 patients had been diagnosed as having stage I disease, 6 stage II and 4 stage III. Two patients had two SRS studies during the course of their disease. SRS was performed with Indium-111 pentetreotide (Octreoscan), a radiolabelled somatostatin analogue. Patients were treated according to the clinical stage. A regular follow-up was scheduled every three months.SRS depicted stage I and II MCC tumour sites with an overall sensitivity of 78% (95% confidence interval (CI): 40%-97%) and a specificity of 96% (81%-100%). The histopathological diagnosis was used as the gold standard. Sites visualised by SRS were compared to those detected with conventional modalities and to follow-up data for all stages: SRS visualised four out of five primary tumour sites, six out of eight lymph node sites, no skin metastases (14 sites in 2 patients), two out of three thoracic metastases and zero out of two hepatic metastases. SRS did not influence treatment decision-making in any of the cases.Although SRS seems highly specific in MCC and could be of help in difficult cases, it cannot be recommended for routine evaluation.

Recent improvement in the understanding of the mechanisms involved in the response to ionizing radiation have made it possible to identify new therapeutic targets to increase the anti-tumor efficacy or, alternatively, to decrease the effect on normal tissues. These approaches included targeting genes involved in the regulation of radio-induced DNA-repair and cell death as well as genes involved in the regulation of radio-induced apoptosis. Many other molecular targets have been recently identified to potentially interfere with the response to ionizing radiation, such as some cell membrane growth factor receptors (EGFr, TGFb) or molecules involved in intra-cellular signal transduction pathways, cell cycle regulation, etc. In addition, other promising ways to modulate radiation-induced response concern extracellular or tissue factors such as hypoxia and angiogenesis.

Validation of biological dosimetry versus physical dosimetry in malignant haemopathy patients conditioned by total body irradiation (TBI) before bone marrow transplantation (BMT).The scoring of chromosomal aberrations in peripheral lymphocytes irradiated in vivo was used to perform the biological dosimetry. The data were compared to those obtained with healthy volunteers' total blood exposed to in vitro irradiation with linear accelerator doses (0.2, 0.5, 0.75, 1, 2, 3, 4 and 5 Gy) for dose-response curves. In experimental animal models, can in vivo and in vitro responses be considered as being the same? All the published human data are based on retrospective dose evaluation with very large uncertainties on the dose precisely delivered to the subject. TBI before BMT was taken as a model where the dose calculation results from the physical method, with homogeneous beam and dose delivered precisely along the entire organism. In vivo response allows us to validate biological dosimetry in 15 adult patients (female + male), before (D = 0 Gy) and after the first fraction of 1.8 Gy, delivered by a linear accelerator (18 MV, dose-rate of 15.8 cGy/min-1). Two methods, conventional cytogenetics (CCG) and fluorescent in situ hybridization (FISH painting) of chromosome 4 were respectively used to analyze the unstable chromosome aberrations and stable chromosome aberrations.Healthy volunteer lymphocytes, before irradiation, yielded 0.1% dicentrics and 0.3% translocations of chromosome 4, with 2.5% for the whole genome. Patients before irradiation had 2% dicentrics and 11.48% chromosome 4 translocations for the whole genome. In the 15 patients, for a physical dose of 1.8 Gy, the evaluated biological dose was 1.93 Gy (95% CI: 1.85-2.05 Gy) with conventional cytogenetics and 2.06 Gy (95% CI: 1.75-2.15 Gy) with FISH.These results, in which the biologically estimated dose is in complete agreement with the dose calculated by physical dosimetry in the homogeneous irradiation model, suggest the validation of biological dosimetry in TBI conditioning.

Context For several years, French comprehensive cancer centers (CCCs) have been committed to projects to improve security, quality and efficiency of radiotherapy. An improvement program in the radiotherapy departments of CCCs, including Professional Practice Appraisal, has been set up. Objectives This campaign aims at improving quality of care in radiotherapy departments in all CCCs. It also anticipates the obligations binding institutions to obtain a radiation therapy agreement. The method is based on benchmarking: To establish a diagnosis To share experiences To set up improvement projects To demonstrate the progress made Program 13 quality indicators (QIs) have been developed with the participation of experts. They address treatment waiting times, multiprofessional treatment decision, treatment preparation, execution of treatment and follow-up. These QIs allow a qualitative assessment of the different steps in patient care. Method In each of the 20 CCCs, 80 medical records were included from patients treated by radiotherapy for a non inflammatory non metastatic breast cancer. Assessment could just been done on traceability, which is only indirectly related to quality of practice. To identify weaknesses and the corrective actions needed, each CCC analysed first its own QI measures from a local point of view and then in comparison with other centers. The corrective actions can be different from center to center depending on the anomalies and the ability to resolve them. Selected actions of improvement, according to a prioritisation process (costs, objectives and concerned professionals or departments), have been implemented. A schedule for these implementations was established in each CCC. Whenever possible, corrective actions and optimised processes were shared between the CCCs. Results The results of the CCCs regarding these indicators show some heterogeneity in practices: the end treatment report and the post treatment consultation were available in 98% and in 93% of the medical records respectively. The rate of patient enrolment in clinical trials was 13%. The variability of these quality indicators between the 20 CCCs shows that they are discriminative. The fact that some teams obtained a 100% rate for different QIs reflects that this is achievable. Conclusion The impact of this implementation campaign will be assessed one year after, using the same indicators. By defining such QIs we are able to follow programs for improving the quality and the security of treatment closely. The measurement of developed QIs allows us to improve the quality of patient care by improving management procedures. It encourages health care professionals to be aware of their practices and of the legal obligations. It also has the advantage of implicating all the professionals involved in patient care. Contexte Depuis plusieurs annees les CLCC sont impliques dans des travaux visant l9amelioration de la securite, de la qualite et de l9efficience, en radiotherapie. Un programme de renforcement de la qualite dans les departements de radiotherapie des 20 CLCC, comportant plusieurs volets, dont l9evaluation des pratiques professionnelles (EPP) des equipes de radiotherapie, est mis en place dans les CLCC. Objectifs Cette demarche d9EPP vise a ameliorer la qualite de la prise en charge en radiotherapie dans les centres et anticipe les obligations opposables aux etablissements en radiotherapie dans le cadre du dispositif d9autorisation pour le traitement du cancer. La methode de cette demarche repose sur la comparaison pour l9amelioration (benchmarking), qui permet: d9etablir un diagnostic de partager les experiences de declencher la mise en place d9actions d9amelioration de montrer les progres realises. Programme Developpes en collaboration avec un groupe d9experts professionnels, les travaux realises ont vise a elaborer 13 indicateurs. Ils concernent les delais de mise en œuvre, la qualite des propositions therapeutiques (reunion de concertation pluridisciplinaire), la conformite de la preparation, les bonnes pratiques de traitement et de surveillance per et post irradiation, ce qui permet une analyse qualitative de toutes les etapes de la prise en charge du patient. Ces outils ont fait l9objet d9une validation professionnelle Methodologie Dans chacun des 20 CLCC, 80 dossiers de patientes ayant un cancer infiltrant non inflammatoire sans metastase dont le primotraitement comporte une irradiation realisee au sein du centre pendant la periode d9inclusion ont ete etudies. A partir de la 1re mesure, l9analyse des resultats individuels et comparatifs permet a chaque centre d9identifier ses points faibles, necessitant des actions correctives. Ces actions sont variables en fonction des specificites et opportunites de l9etablissement. En fonction de la problematique et de la faisabilite (couts, resultats attendus, personnes ou services impliques), un choix est fait parmi les actions correctives. L9etablissement met alors en œuvre les actions d9amelioration retenues. Un tableau de bord permet a chaque centre de suivre l9avancement de son plan d9actions. Un partage des actions d9amelioration entre les Centres est prevu, lors de journees de presentation des resultats, et une mutualisation des process, des qu9elle est possible, est realisee. Les ameliorations liees aux actions correctives mises en œuvre seront objectivees lors du 2e recueil. Dans l9intervalle, chaque Centre a identifie des points d9amelioration et met en œuvre les actions d9amelioration retenues. L9evaluation n9est realisee que sur les pratiques tracees, il ne s9agit donc que d9une evaluation indirecte de la qualite de la pratique. Resultats La position des CLCC au regard de ces indicateurs traduit une heterogeneite des pratiques : par exemple, le compte rendu de fin de traitement est present dans 98% des dossiers; la consultation de suivi post-traitement est tracee dans 93% des dossiers; le taux d9inclusion dans un essai clinique est de 13%. La variabilite du classement des 20 centres selon les indicateurs montre que les indicateurs sont discriminants et que la faisabilite de l9objectif est de 100%. Conclusion La definition des indicateurs permet ainsi le suivi du programme de renforcement de la qualite et permet la perennisation du cycle d9amelioration de la qualite. De tels indicateurs permettent d9ameliorer la prise en charge des patients par l9amelioration de la gestion des processus, mais aussi par le focus impose aux professionnels sur leurs pratiques et les contraintes reglementaires les encadrant, et enfin par le caractere multiprofessionnel des equipes projets.

Recent data have shown that the in vitro and in vivo cytotoxicity of bioreductive drugs could be significantly increased by combination with ionising radiation or chemotherapy. Various parameters such as oxygen tension and timing of administration of the drugs could play a crucial role in the efficacy of combined treatment modalities. The aim of this study was to define the oxygen dependency of cell survival after in vitro irradiation and incubation with tirapazamine, a bioreductive drug, and cisplatin given alone or simultaneously. Two human cell lines were studied: one cell line sensitive to tirapazamine, Na11+, a pigmented melanoma with a high percentage of hypoxic cells, and a less sensitive cell line to tirapazamine, HRT18, a rectal adenocarcinoma. Gas changes were made to study cell survival at four different oxygen concentrations (pO2): air (20.9% O2), 10.2 and 0.2% O2. Cells were incubated with tirapazamine and cisplatin alone or combined for one hour at 37 degrees C, then irradiated and cultured. For Na11+, cell survival after irradiation was comparable in air and at 10% oxygen with the two drugs given alone or combined. At 2 and 0.2% oxygen, cell killing was largely increased by tirapazamine and was not modified by the addition of cisplatin. For HRT18, cell survival was not modified when cisplatin was added to radiation, whatever the oxygen partial pressure. At low pO2 (2 and 0.2%) the cytotoxic effect of tirapazamine was not significantly decreased by the addition of cisplatin. When cytotoxic and bioreductive drugs are combined to radiation, the magnitude of the observed effect is highly dependent on the partial oxygen pressure and on the sensitivity of the cell line to the individual drugs. This has very important implications for clinical strategies based on combined chemo-radiotherapy.

Meningeal involvement is frequent in metastatic melanoma, approximately 30% in autopsy series. Functional signs may be misleading and the neurological examination may be normal. Certain diagnosis requires identification of tumor cells in the cerebrospinal fluid. CSF cytology is however sometimes negative and magnetic resonance imaging (MRI) with gadolinium injection may provide the diagnosis. The aim of this retrospective study was to assess the role of imaging in the diagnosis of leptomeningeal carcinomatosis.The diagnosis of leptomeningeal carcinomatosis was made in 8 patients between 1992 and 1998. All had signs of neurological function impairment, but the neurology examination was abnormal in only 2.Cytology examination of the cerebrospinal fluid provided the diagnosis of leptomeningeal carcinomatosis in 5 patients. One out of 5 brain CT scans were positive, showing meningeal enhancement confirmed by brain MRI. The spinal tap was not contributive in 2 cases and was not done in 1. In these three cases, the brain CT did not provide any diagnostic element while the brain MRI with gadolinium injection confirmed the diagnosis of leptomeningeal carcinomatosis.Forty-one percent of patients with autopsy proven leptomeningeal carcinomatosis have a normal ante mortem spinal tap. Brain MRI with gadolinium injection has better sensitivity than brain CT scan. All patients with nonspecific neurological signs and a normal spinal tap should be explored with a brain MRI.

Hypoxic cells are present in rodent and xenografted human tumours and it has been known for a long time that the absence of oxygen in tumours is a factor of resistance against ionising radiation. The dose modifying role of oxygen (oxygen enhancement ratio) has been largely studied in experimental models. For pO2 values of 2 mmHg, the relative radiosensitivity of tumour cells is intermediate between the maximum sensitivity observed in air and the minimal one observed in hypoxia. The measurement of tumour pO2 in patients (polarographic technique) has demonstrated the presence of low values (10 mmHg) in many different tumour sites (ENT, uterine cervix, breast, melanoma, etc). In order to sensitise hypoxic tumours, imidazole have been used in patients, but most of the results were negative. New methods have been developed in the combination of bioreductive drugs of cytotoxic cells to radiotherapy. In this article, we will describe the clinical results obtained in patients with radiosensitising chemical agents.

Microcystic adnexal carcinoma is a recently described malignant neoplasm of adnexal structure. It remains frequently misdiagnosed. These tumors are characterized by their slow progression and by local aggressivity with local recurrences. The best treatment appears to be surgical excision with microscopically controlled margin. We report two cases of microcystic adnexal carcinoma recently observed at Institute Gustave Roussy.

Ollier's disease is a rate affliction (not more than approximately 100 cases have been reported over a 30-year period) characterized by bone dysplasia in which evolution to degenerative neoplasia has been described. Diagnosis of chondrosarcoma is delicate in these cases. It is a kind of slowly evolving low grade malignant tumor. Surgery is the primary treatment course, and can lead to remission. Prognosis, depending on the number and dimension of the lesions, their localization and metastasis prevention, is usually good, but relapses are relatively frequent: 25 to 50%. In case of relapse, radiotherapy and chemotherapy were tested but their efficacy is limited. We report here two clinical cases and discuss literature data.

The daily practice of radiation oncology is increasingly influenced by the late tolerance of normal tissues. The treatment decision must be based on detailed arguments and the physician's duty to extensively inform his patients is emphasised every day. The incidence and severity of radiation-induced sequelae and late complications can be reduced by decreasing the total dose to the normal tissues, and by decreasing the dose protraction, provided that the interval between fractions remains longer than 6 to 8 hours. This approach yields a selective protection of late responding normal tissues, since tumours are less sensitive to the effects of fractionation. Despite its own limitations, the linear- quadratic model is nowadays the standard method to compare the biological effects of different radiation treatments.

Between January 1956 and December 1990, 17 patients younger than 17 years with available pathological screens of de novo cutaneous melanoma, and with no other risk factors (xeroderma pigmentosum, giant congenital naevi, congenital melanoma or a proven family history of dysplastic naevus syndrome) were seen at the Gustave-Roussy Institute. The median age was 9 years and 9 months (range 2 years and 3 months-16 years and 9 months). The primary disease was located in the lower extremities in 10 cases, the trunk in five cases, and the upper extremities or head and neck in one case. The disease was localized for 10 patients at presentation (stage I), six had proven nodal metastasis (stage II) and one patient had nodal and breast metastases. The median thickness of the primary lesion was 2.89 mm (range 0.64-10). Five tumours were at level III on Clark's index, eight at level IV and four at level V. Six cases were classified as superficial spreading, two as unclassified radial growth, three nodular, three with Spitzoid cells, and three were unclassified. Two patients presented local recurrence with an initial unclassified melanoma, with a thickness greater than 2.5 mm. At a median follow-up time of 7 years, two patients had died from recurrent disease, and one patient had died from a second malignancy.

Solid human tumours contain areas with low oxygen tension (pO2). For bioreductive drugs it is important to define the cytotoxic effect according to drug concentration and to clinically relevant pO2. In this study, the pO2 dependence of the survival of three human cell lines (HRT 18, Na11 +, and MEWO), exposed to tirapazamine (SR-4233) alone or combined with ionizing radiation, was studied in vitro. Gas changes were made to obtain five different oxygen concentrations: air (20.9% O2), 10, 2, 0.2 and 0.02% O2 (hypoxia). Tirapazamine below a concentration of 100 microM was not cytotoxic in air or at 10% O2. At 100 microM tirapazamine was toxic in 2% O2, and at 50 microM in 0.2% O2. For pO2 < 0.2% O2, there was a marked increase in cell killing when 10 microM tirapazamine was combined with 2 Gy, compared with either 10 microM or 2 Gy given alone (p < 0.03). The cytotoxic effect of tirapazamine on human tumour cells in vitro is highly dependent on clinically relevant pO2's. The activation of tirapazamine at a low concentration and at a pO2 found mainly in tumours could yield a very beneficial therapeutic ratio.

From 1974 to 1992, 1245 patients with cervix carcinoma were treated at the Institut Gustave-Roussy using several treatment protocols all of which included LDR brachytherapy. We present and discuss the results of our experience.

In the field of radiation oncology, equipments for fractionated stereotactic radiotherapy and single-dose radiosurgery have become increasingly accurate. Out of brain lesions, extracranial stereotactic treatments are more and more frequently considered. New imaging techniques (spect MRI, PET) provide further relevant information to slice images (CT-Scan, MRI). However, the treatment of extracranial lesions needs to take into account organ mobility (tumor and healthy tissue) whilst retaining the ability of stereotactically locating the target. Real time tracking systems allow to keep high conformality to moving and deforming targets. Currently, the most significant developments are in the field of extracranial stereotactic radiotherapy in lung, liver and prostate cancers, together with re-irradiation and oligo metastases. Recent data will be presented.

Uterine cervix carcinoma is considered by some authors to carry a poor prognosis in young patients (35 years of age). From 10 years, many series have been published with divergent conclusions. However, a group of patients with poor prognosis could be individualized; age30 years, locally aggressive tumour, poorly differentiated, nodal involvement, amplification of c-Myc proto-oncogene. New imaging technics and coelioscopy could help to the diagnosis. The role of combined treatment remains to be demonstrated and biological factors (kinetics, oxygenation) will help in the future to more adapted treatments.

The acute effects of radiations on normal tissues are linked to known parameters. These parameters are the nature and function of the irradiated organ, and the technical characteristics of the treatment (treated volume, beam energy, fractionation). The intensity and time course of the clinical reactions depend on these parameters. All clinical reactions will be recorded with appropriate systems. Some examples of acute reactions are given.

Brachytherapy has a key role to play in the treatment of bladder carcinoma. It is generally combined with partial bladder resection for limited tumours (T1-2, N0, M0). Results obtained in Holland and France have shown 80% local control with limited morbidity.

Carcinomas of the male and female urethra are serious cancers because they frequently present late with lymph node involvement. Brachytherapy plays a significant role, often associated with external beam irradiation and surgery, in the conservative management of these tumors. This radiation treatment uses a catheter or a vaginal mould applicator for intraluminal/intracavity brachytherapy, and hypodermic needles or guide gutters for the interstitial portion. The radioactive source usually employed is iridium 192. The total dose administered is usually between 60 and 70 Gy. Disease free survival is 50%, local control 70%, and the complication rate is 20%.

While there is little doubt today that untreated human tumors contain areas of hypoxic cells, the influence of hypoxia in radiotherapy is much more difficult to demonstrate. There is a great deal of clinical and experimental research activity with, perhaps, closer cooperation between clinicians and scientists than in the past. Intratumor hypoxia can be quantified by several methods. If it si shown that hypoxia is correlated with local control for some types of tumors, and that hypoxia is really a factor of radioresistance in man, the current development of low-toxicity compounds such as perfluorochemical compounds or nicotinamide should result in improved radiotherapy results. 145 refs., 2 figs., 4 tabs.

Brachytherapy can represent the exclusive treatment of localized prostatic adenocarcinoma. Several techniques have been described: permanent implantations with 125-iodine or 198-gold seeds or temporary implantations with 192-iridium. These implantations are performed either via a retropubic approach, often combined with pelvic lymphadenectomy, or via a transperineal approach, with or without ultrasound guidance. The largest clinical experience is from Memorial Sloan-Kettering Cancer Center, with 1119 patients treated from 1970 to 1985 for stage B or C prostatic adenocarcinoma with pelvic lymph node dissection and interstitial iodine-125 brachytherapy. The 15-year overall local control is 51%. One of the strongest prognostic factors is lymph node involvement. The comparison between brachytherapy and other treatment modalities such as radical prostatectomy or external irradiation or even expectant management in localized tumors has never been performed prospectively. This type of randomized trial appears to be necessary in the assessment of the results published with brachytherapy.

Tumors of the tonsillar Fossa classed T1T2 are generally treated by irradiation with high rates of local control. Patient survival is related to the risk of developing distant metastatic disease and second head and neck cancers. The use of induction chemotherapy for squamous cell carcinoma of the head and neck gives a high rate of clinical tumor response and for this reason, it is increasingly used in standard treatment regimens. However, the long term results in terms of improved local control and improved survival (from a decreased rate of metastases) has not been clearly demonstrated. In addition, the toxicity of primary chemotherapy is not negligible. After review of the literature, the role of induction chemotherapy should be evaluated only in reference to randomized trials.