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Biomedical subjects

D Pontvert

Publications and source records attributed to D Pontvert.

At least 19 recordsLinked to original sources

Combination of photon and proton radiation therapy for chordomas and chondrosarcomas of the skull base: the Centre de Protonthérapie D'Orsay experience.

PURPOSE: Prospective analysis of local tumor control, survival, and treatment complications in 44 consecutive patients treated with fractionated photon and proton radiation for a chordoma or chondrosarcoma of the skull base. METHODS AND MATERIALS: Between December 1995 and December 1998, 45 patients with a median age of 55 years (14-85) were treated using a 201-MeV proton beam at the Centre de Protonthérapie d'Orsay, 34 for a chordoma and 11 for a chondrosarcoma. Irradiation combined high-energy photons and protons. Photons represented two-thirds of the total dose and protons one-third. The median total dose delivered within the gross tumor volume was 67 cobalt Gray equivalent (CGE) (range: 60-70). RESULTS: With a mean follow-up of 30.5 months (range: 2-56), the 3-year local control rates for chordomas and chondrosarcomas were 83.1% and 90%, respectively, and 3-year overall survival rates were 91% and 90%, respectively. Eight patients (18%) failed locally (7 within the clinical tumor volume and 1 unknown). Four patients died of tumor and 2 others of intercurrent disease. In univariate analysis, young age at time of radiotherapy influenced local control positively (p < 0.03), but not in multivariate analysis. Only 2 patients presented Grade 3 or 4 complications. CONCLUSION: In skull-base chordomas and chondrosarcomas, the combination of photons with a proton boost of one-third the total dose offers an excellent chance of cure at the price of an acceptable toxicity. These results should be confirmed with a longer follow-up.

Adolescent↗

Proton beam therapy (PT) in the management of CNS tumors in childhood.

At the Centre de Protontherapie d'Orsay, nine children with intra-cranial malignancies were treated between July 1994 and January 1998. Immediate and late tolerances were excellent in all cases (follow-up 2 to 50 months). Two patients recurred locally (marginal failures), seven are alive and doing well. At Loma Linda, 28 children were treated between 1991 and 1994, 16 for a benign tumor of the brain and twelve for a malignant one. With a follow-up of seven to 49 months, three patients died (grade 2 to 4 gliomas), one is living with a persistent disease. Four children had treatment-related toxicity (one cataract, two hormonal failures and two seizures). The other children are doing well. At MGH Boston, 18 children with skull base-cervical spine chordomas have been reported. At five years, actuarial survival and disease-free survival have been 68 and 63%, respectively. Children with cervical sites had a worse prognosis (p = 0.008). Four children had radiation-related morbidity: two pituitary failures, one temporal lobe necrosis, one temporal muscle fibrosis. In this experience, such rare tumors seemed to behave in children like in adults.

Adolescent↗

[Localized or metastatic cancer of the prostate: review of new treatment modalities].

Amongst men, prostatic adenocarcinoma is the most common cancer and the second most frequent cause of deaths. Widespread PSA measurement have led to earlier diagnosis. Recent clinical trials have tried to show an improvement in the prognosis. Early stages are mainly treated surgically even if local control results are similar with radiotherapy. Radiotherapy is the main stay of treatment for more locally advanced disease, either conventionally or conformational. Adjuvant hormonotherapy has been shown to improve survived as opposed to neoadjuvant hormonotherapy which only has local effects. The treatment of metastatic disease is palliative with the use of antiandrogens. In case of relapse, a second line of hormonotherapy or a chemotherapy is given. However the problem is the lack of effective drugs. Response rates to the main drug treatment are around 10 to 20%. New therapeutic approaches are now based on antimicrotubules agents but it is difficult to evaluate their efficacity. Further clinical trials will provide more information about improvement in survival rates and in quality of life.

Humans↗

Automatic three-dimensional expansion of structures applied to determination of the clinical target volume in conformal radiotherapy.

PURPOSE: A method is provided for the automatic calculation of the Clinical Target Volume (CTV) by automatic three dimensional (3D) expansion of the Gross Tumor Volume (GTV), keeping a constant margin M in all directions and taking into account anatomic obstacles. METHODS AND MATERIALS: Our model uses a description of the GTV from contours (polygons) defined in a series of parallel slices obtained from Computed Tomography (CT) or Magnetic Resonance Imaging (MRI). Each slice is considered sequentially, including those slices located apart from the GTV at a distance smaller than M. In the current slice a two-dimensional (2D) expansion is performed by transforming each vertex of the polygon into a circle with a radius equal to M, and each segment into a rectangle with a height equal to 2M. A cartesian millimetric grid is then "projected" onto the slice and a specific value is assigned at each point depending if the point is internal to the 2D expansion. The influence in the current slice of any slice located at a distance delta z smaller than M is taken into account by applying a 2D expansion using a margin [formula: see text]. Additional contours representative of various "barriers" stopping the expansion process can also be defined. RESULTS: The method has been applied to cylindrical and spherical structures and has proven to be successful, provided that the slice thickness is small enough. For usual slice thicknesses and margins, it gives a slight overestimation of the additional volume (around 5%) due to the choice that the calculated target volume would not be less than the expected volume. It has been shown that for a spherical volume, a 2D expansion performed slice by slice leads to a volume up to 80% smaller than that obtained by 3D expansion. CONCLUSIONS: This tool, which mimics the tumor cell spreading process, has been integrated in our treatment-planning software and used clinically for conformal radiotherapy of brain and prostatic tumors. It has been found to be extremely useful, not only saving time but also allowing a precise determination of the CTV which would be impossible to do manually.

Algorithms↗

Clinical applications of proton therapy.

Proton therapy offers considerable potential advantages in the management of poorly resectable, radio-resistent tumors close to critical anatomical structures. So far over 15,000 patients have been treated worldwide with two major indications: conservative management of ocular melanomas in which local control exceeds 95% at 5 years and curative irradiation of sarcomas at the base of the skull and cervical canal, with a survival rate between 84 and 94% at 5 years. The different protocols tested currently worldwide are discussed.

Adolescent↗

Potential of T2 relaxation time measurements for early detection of radiation injury to the brain: experimental study in pigs.

PURPOSE: To investigate the MR T2 relaxation time and histologic changes after a single-fraction 25-Gy dose of radiation to the brain of pigs. METHODS: The right hemisphere of 10 Meishan pigs was irradiated with a single dose of 25 GY at the 90% isodose, using a 12-MeV electron beam. T2 relaxation time was measured within three regions of interest in the brain: those that had received 90%, 70%, and 40% of the total dose, respectively. T2 kinetics over time was compared with histologic studies. RESULTS: Brain T2 values were noted to increase within the irradiated areas. T2 kinetics were analyzed in three phases: an immediate transient phase and two long-lasting phases. These two long-lasting phases were correlated with the detection of ventricular compression and necrosis, respectively. The T2 increase within the 90% region of interest was 19%, 22%, and 26% for phases I, II, and III, respectively. T2 measurements within other regions of interest were not significant. CONCLUSION: Although our results suggest a dose threshold for T2 variations, brain T2 values increased after irradiation at a level at which disease could not be seen on conventional MR images. This illustrates the value of using conventional MR imaging in a quantitative manner to assess molecular tissue abnormalities at earlier stages of developing diseases.

Animals↗

Quantitative magnetic resonance and isotopic imaging: early evaluation of radiation injury to the brain.

PURPOSE: Using magnetic resonance (MR) and isotopic imaging to investigate the cerebral alterations after highdose single-fraction irradiation on a pig model. We assessed the nuclear magnetic resonance (NMR) relaxation times as early markers of radiation injury to the healthy brain. METHODS AND MATERIALS: A total of 17 animals was studied; 15 irradiated and 2 unirradiated controls. Pigs were irradiated with a 12 MeV electron beam at a rate of 2 Gy/min. Ten animals received 40 Gy at the 90% isodose, five animals received 60 Gy, and two animals were unirradiated. The follow-up intervals ranged from 2 days to 6 months. T1-weighted scans, T2-weighted scans, and scintigrams were performed on all animals to study neurological abnormalities, cerebral blood flow, and blood-brain barrier (BBB) integrity. T1 and T2 relaxation times were measured in selected regions of interest (ROIs) within the irradiated and contralateral hemispheres. A ratio T1 after irradiation/T1 before irradiation, and a ratio T2 after irradiation/T2 before irradiation, were calculated, pooled for each dose group, and followed as a function of time after irradiation. RESULTS: Scintigraphy visualized the brain perfusion defect and BBB disruption in all irradiated brains. The ratio T2 after irradiation/T2 before irradiation was proportional to the effective dose received. The T2 ratio kinetics could be analyzed in three phases:an immediate and transient phase, two long-lasting phases, which preceded compression of the irradiated lateral ventricle, and edema and necrosis at later stages of radiation injury, respectively. The magnetic resonance imaging (MRI) observations correlated well with histological analysis. CONCLUSION: The results show that quantitative imaging is a sensitive in vivo method for early detection of cerebral radiation injury. The reliability and dose dependence of T2 relaxation time may offer new opportunities to detect and understand brain pathophysiology after high-dose single-fraction irradiation.

Animals↗

Clinical applications of proton therapy. Experiences and ongoing studies.

Proton therapy offers potentially considerable advantages in the management of slow-growing, poorly resectable or non-resectable tumors resistant to x-rays and located close to critical radiosensitive anatomical structures, such as the brain stem of the spinal cord. Among over 13,000 irradiated patients in the USA, Europe, and Japan, two major clinical indications have been documented: 1. The conservative management of choroidal melanomas, in which 98% 5-year local control can be expected at the price of low toxicity and visual preservation in approximately half of them. 2. The curative management of low-grade chondrosarcomas and chordomas of the base of the skull and cervical spine, leading to, in combination with maximal tumor resection, 84%-94% long-term survival. Other ongoing studies concern prostate, head and neck carcinomas as well as various intracranial tumors. Radiosurgical programs are being conducted generally with single fractions and under stereotactic conditions.

Bone Neoplasms↗

Experimental MR study of cerebral radiation injury: quantitative T2 changes over time and histopathologic correlation.

PURPOSE: To use the pig brain as a large-animal model to examine the effects of high-dose single-fraction irradiation on MR images, T2 relaxation time, and histologic integrity. METHODS: A total of 24 Meishan pigs were studied: 20 irradiated animals and 4 unirradiated controls. A high dose was delivered to the right hemisphere of the animals, using a 12-MeV electron beam. Ten animals received 40 Gy at the 90% isodose, and 10 animals received 60 Gy. Quantitative measurement of T2 relaxation time was compared with qualitative analysis of T2-weighted images and histologic studies. RESULTS: Quantitative analysis revealed a reproducible increase of the T2 parameter within the irradiated areas. The T2 kinetic could be analyzed in two phases, which appeared before the visualization of ventricle compression, necrosis, and edema. The first is characterized by vascular inflammation and the latter by radiation necrosis and edema. Both are dose dependent. CONCLUSION: These results underline the ability of quantitative MR for early diagnosis of brain radiation lesions in vivo.

Animals↗

Is reseeding from the primary a plausible cause of node failure?

In a previous analysis of node failures in 1251 consecutive patients with node positive oropharyngeal and pharyngolaryngeal squamous cell carcinomas treated by external radiotherapy alone at the Institut Curie, the main reasons for patient exclusion were node recurrence associated with primary failure (N+T failures) and doses less than 55 Gy. These exclusions reduced the number of node failures from 399/1251 (32%) to 77/798 (10%). Multivariate analysis of node recurrence indicated that node size and fixity, treatment duration, and T stage of primary were significant (higher probability of isolated node failure for the T1-T2 primaries). In the present analysis, it is noted that 60% of the N+T failures were observed less than 1 month after the completion of the irradiation and, therefore, were not likely the result of reseeding from the primary tumor. When all 1251 patients were included in the analysis, the probability of nodal failure increased for larger nodes, T4 primaries, lower nodal doses, presence of contralateral node metastases, and nodal fixation to the surrounding structures. No influence of the primary site was found. Treatment duration was closely associated with total dose to the nodes. The best description of the data was obtained with a model including total dose and not treatment time. However, as in the previous analysis, the exclusion of low-dose (less than 55 Gy) treatments resulted in the loss of a significant dose-control relationship. We conclude that the majority of node failures is unlikely to result from reseeding from the primary tumor, and therefore should not be excluded from local-control analyses. From a more radiobiological point of view, the exclusion of palliative treatments is questionable when studying the effect of dose on local control.

Adult↗

Quality control of radiotherapeutic treatment of medulloblastoma in a multicentric study: the contribution of radiotherapy technique to tumour relapse. The French Medulloblastoma Group.

Between 06.86 and 11.89, 88 medulloblastoma or primitive neuroectodermic tumour (PNET) localised in the posterior fossa have been included in the M7 multicentric protocol, 82 received the totality of the radiotherapy treatment and were evaluable for this study. Twenty-two of these 82 patients relapsed: their radiotherapy treatment is analysed in the present study. In 10 cases out of the 22 relapses treatment failure was probably due to a radiotherapeutic imperfection. This study confirms the necessity of a strict radiotherapy control, particularly in multicentric study.

Adolescent↗

Induction chemotherapy in advanced head and neck tumors: results of two randomized trials.

From March 1983 to December 1989, 208 patients with locally advanced squamous cell carcinoma of the head and neck were successively included into two randomized induction chemotherapy trials. The chemotherapy regimen of the first trial, which included 100 patients, consisted of two cycles of a combination of cisplatin, bleomycin, vindesine and mitomycin C; while that of the second trial, which included 108 patients, consisted of three cycles of a combination cisplatin, 5-fluorouracil by continuous infusion and vindesine. Local treatment was the same in the two trials: primary radiotherapy in all patients. The response was then evaluated; in the case of a poor response at 55 Grays surgery was performed; otherwise, radiotherapy was continued to full doses (possibly followed by salvage surgery). The tumor and lymph node responses to chemotherapy (complete and partial response) were higher in the second trial than in the first: 70% versus 50% for primary lesions, 47% versus 25% for lymph nodes. The toxicity of the two chemotherapy regimens was minimal. In the two trials, an initial major response to chemotherapy predicted subsequent efficacy of irradiation in 80% of the patients. The significance of the complete response at the end of the irradiation varies with the previous response to the chemotherapy. With a median follow-up of 60 months with the first chemotherapy regimen and 30 months with the second, overall survival and disease-free interval were very similar in the two groups. The incidence of distant metastasis was significantly reduced (p less than 0.03) with chemotherapy. This trial suggests the need to test new chemotherapy protocols according to new schemes of treatment, with chemotherapy given concurrently with or following the completion of standard treatment by means of multicenter randomized trials.

Antineoplastic Agents↗

Results of radiation therapy in carcinoma of the base of the tongue. The Curie Institute experience with about 166 cases.

Between 1960 and 1980, 166 patients with squamous cell carcinoma of the base of the tongue were treated with primary irradiation at the Curie Institute (Paris, France). Distribution according to the TNM system 1978 International Union Against Cancer (UICC) was the following: 22 T1 lesions, 47 T2 lesions, 64 T3 lesions, and 33 T4 lesions. Regional nodes were not palpable in 50 cases, 35 had N1 nodes, 12 had N2 nodes, and 69 had N3 nodes. All patients received external beam radiation. The 2-year, 3-year, and 5-year overall survival rates for all patients were, respectively, 45%, 37%, and 27%. Local control was significantly related to the initial status of the primary, to the tumor regression at the end of the radiation therapy, and to the histologic differentiation. The 2-year local control was 96% for T1 lesions, 57% for T2 lesions, 45% for T3 lesions, and 23% for T4 lesions. Local control was 70% if the tumor regression was complete at the end of the treatment and 27% if the tumor regression was partial. No significant differences were found in primary local control with respect to degree of infiltration, age, and dose of radiation therapy over a dose of 60 Gy in 6 weeks. The 3-year regional control was 86% for N0, 78% for N1, and 60% for N2 and N3. Among the tumor characteristics analyzed, the most useful ones for predicting local control and survival were clinical tumor staging parameters and tumor radiation-induced regression. A new therapeutic approach based on the evaluation of the tumor regression at 50/55 Gy is under discussion.

Adult↗

Impact of cervical disease and its definitive radiotherapeutic management on survival: experience in 2013 patients with squamous cell carcinomas of the oropharynx and pharyngolarynx.

Two thousand thirteen patients with squamous cell carcinoma of oropharynx and pharyngolarynx were reviewed with regard to neck disease presentation and disease-free survival after radical radiotherapy. All patients were staged according to both the AJCC 1976 and the UICC 1978 classifications. Causes of failure, disease-free survival, and complication rates were assessed. Sixty percent had a clinically positive neck. The 3-year disease-free survival rates were 58%, 44%, 38%, and 25% for AJCC N0, N1, N2, and N3 cases, respectively. Corresponding UICC figures were 58%, 46%, 26%, and 29%. Analyzed parameters were nodal stage, size, site and fixity, and location of primary. Complications attributed to neck disease did not exceed 3%. A critical appraisal of the nodal staging systems is derived from these sets of data.

Carcinoma, Squamous Cell↗