[PET/CT and biochemical recurrence of prostate adenocarcinoma: Added value of 68Ga-PSMA-11 when 18F-fluorocholine is non-contributive]. / TEP/TDM et récidive biologique d'adénocarcinome prostatique : apport du 68Ga-PSMA-11 lorsque la 18F-fluorocholine n'est pas contributive.

INTRODUCTION: Since April 201, we have introduced PET/CT using a ligand of prostate-specific membrane antigen labeled with gallium-68 (PSMA-11). We aimed to evaluate its positivity rate and impact in patients presenting biochemical recurrence of prostate cancer whose 18F-fluorocholine (FCH) PET/CT was non-contributive. PATIENTS AND METHOD: Patients were prospectively included between April and December 2016. PET/CT was performed 60min after injection of 2MBq/kg of body mass of 68Ga-PSMA-11. Three anatomical areas were considered: prostatic lodge, pelvic lymph nodes and distant locations. The impact of PSMA-11 PET/CT was assessed by comparing changes in therapeutic strategy decided during multidisciplinary meeting. RESULTS: Thirty-three patients were included. The mean PSA serum level measured on the month of the PSMA-11 PET/CT was 2,8ng/mL. Twenty-five (76%) PSMA-11 PET/CT were positive, 7 (21%) negative and 1 (3%) equivocal. Of 11 patients whose FCH PET/CT showed equivocal foci, PSMA-11 PET/CT confirmed those foci in 5 cases. Follow-up was available for 18 patients (55%). PSMA-11 PET/CT results led to a change in management in 12 patients (67%). CONCLUSION: 68Ga-PSMA-11 PET/CT is useful in detecting recurrence of prostate cancer, by identifying residual disease which was not detected on other imaging modalities and by changing management of 2 patients out of 3. LEVEL OF EVIDENCE: 5.

[Conformal radiotherapy to 76Gy in localized prostate cancer. Therapeutic modalities and preliminary results]. / Radiothérapie conformationnelle à 76Gy des cancers localisés de la prostate. Modalités thérapeutiques et résultats préliminaires.

PURPOSE: To describe therapeutic modalities for localized prostate cancer treated by conformal radiation to 76Gy with or without androgen ablation. To evaluate the preliminary results in terms of survival, biological control and toxicity. PATIENTS AND METHOD: Between January 1998 and June 2001, 321 patients with localized prostate cancer were irradiated at institut Curie. Tumors were stratified into the three Memorial Sloan-Kettering Cancer Center prognostic groups (1998) for analysis: favorable risk group (FG) 23%, intermediate risk group (IG) 36.5%, unfavorable risk group (UG) 40.5%. Androgen deprivation, mainly neoadjuvant, less or equal to one year was prescribed to 93.8% of patients (72.6% less or equal to six months). Planning target volume prescription doses were: prostate: 76Gy, seminal vesicles: 56 to 76Gy, and pelvic lymph nodes: 44Gy to 16.8% of patients. RESULTS: The five-year actuarial overall survival was 94% (95% IC: 90-97%). The median post-therapeutic follow-up was 36 months (nine to 60 months). The 48-month actuarial rates of biochemical control for the three prognostic groups were statistically different according to both the American Society for Therapeutic Radiology and Oncology consensus (ASTRO 1997) and the Fox Chase Cancer Center definitions of biochemical failure (FCCC 2000) with respectively 87 and 94% for FG, 78 and 84% for IG, 54 and 58% for UG (P<10(-6) and P<10(-8)). At time of our analysis, late post-treatment rectal and bladder bleedings were 17,4 and 13,6%, respectively. According to a 1-4 scale adapted from M.D. Anderson Cancer Center criteria: rectal bleedings were grade 1 (9.6%), grade 2 (6.2%) and grade 3 (1.6%). Bladder bleedings were grade 2 (13%) and grade 3 (0.6%). Analysis of rectal bleeding risk factors showed significant correlations with pelvic lymph nodes irradiation for grade 2 and 3, (P=0.02), and for all grades, a correlation with smaller rectal wall volumes (P=0.03), and greater percentages of rectal wall irradiated to higher doses: 65, 70, 72 and 75Gy (P=0.02, P=0.01, P=0.0007 and P=0.003, respectively). CONCLUSIONS: These results are comparable to those previously reported with the same follow-up. Impact of dose escalation with short androgen deprivation on local control, survival and complications needs longer follow-up and further analysis.

[Permanent implant prostate cancer brachytherapy]. / La curiethérapie du cancer prostatique par implants permanents.

With an experience of more than 20 years for the pionneers (and more than 10 years in France), permanent implant brachytherapy using Iodin 125 seeds is now recognized as a valuable alternative therapy for localized low-risk prostate cancer patients. An extension of the indications of exclusive brachytherapy towards selected patients in the intermediate-risk group is presently under study. Moreover, for patients in the high-risk group, brachytherapy, as an addition to external radiotherapy, could represent one of the best way to escalate the dose for some patients. Various permanent implant brachytherapy techniques have been proposed; preplanning or real-time techniques, loose seeds or stranded seeds, manual or automatic injection of the seeds. The main point here is the ability to perfectly master the procedure and to comply with the dosimetric constraints which have been recently redefined by the Groupe européen de curiethérapie--European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) group. Mid- and long-term results which are now available in the literature indicate relapse-free survival of about 90% at 5-10 years, the best results being obtained with satisfactory dosimetric data. Some comparative data have shown that the incontinence and impotence rates after brachytherapy seemed to be significantly inferior to what is currently observed after surgery. However, a risk of about 3-5% of urinary retention is usually reported after brachytherapy, as well as an irritative urinary syndrome which may be significant and last several months. In spite of those drawbacks, with excellent long-term results and low rates of incontinence and impotence, brachytherapy can be expected to be proposed to an increasing number of patients in France in the next future.

[Clinical and dosimetric analysis of 469 prostate cancer patients treated in France in 2005 by permanent implant brachytherapy using the Iodin 125 seeds IsoSeed Bebig: report to the French Economic committee of health products (CEPS)]. / Analyse clinique et dosimétrique de 469 patients traités en France en 2005 par implantation prostatique de grains d'iode 125 IsoSeed Bebig: rapport pour le Comité économique des produits de santé (CEPS).

A French decree of February 3rd 2005, allowed the Iodin 125 seeds from several companies to be reimbursed after a permanent implantation brachytherapy for a prostate cancer. Within this frame, the French "Comité économique des produits de santé" (CEPS; Economic committee for health products) made mandatory the annual writing and publication of a follow-up study with three main aims; make sure that the seeds were used for prostate cancer patients with criterias corresponding to the national recommendations, analyze the quality of the dosimetric data, and report all side effects, complications and possible accidents. We therefore report here a clinical and dosimetric analysis of 469 patient cases treated in France in nine centers in 2005 with the Iodin 125 IsoSeed Bebig. This analysis shows that: 1) The national recommendations for selecting patients for exclusive prostate brachytherapy have been taken into account in 97% of the cases; 2) The dosimetric quality criterias totally fulfilled the recommendations in a large majority of cases; the intra-operative D90 was found to be superior to 145 Gy in 98% of the patients, and the intra-operative V100 was superior to 95% in 96% of the cases; 3) The early toxicity (mainly urinary) was found to be at the lower range of what is reported in the literature, with in particular a retention rate of 2.4%.

Radiotherapy of pituitary adenomas: state of the art.

Pituitary adenomas represent approximately 12% of intracranial tumors. They are defined as tumors that are functional or nonfunctional and invasive or noninvasive. Therapeutic strategies rely on surgery, medical treatment, and radiotherapy depending on histology. Neither the role of external radiotherapy nor the technique to be used are firmly established. Nonfunctioning adenomas must be operated on to relieve the compression. Prolactin-secreting adenomas are first treated with dopamine agonists, and GH-secreting adenomas are first treated by surgery if excising the complete tumor is possible; otherwise medical treatment is started. The first-line treatment of ACTH-secreting adenomas is surgery; however, in many cases, insufficient control of either secretion or tumoral volume leads to consideration of irradiation. Complications of conventional radiotherapy are well known and fractionated stereotactic radiotherapy appears to be as safe as radiosurgery. The volume to irradiate is still difficult to define, and this parameter can influence the technique chosen for treatment. Because the indications of radiotherapy are still debated, irradiation of pituitary adenomas must be decided by the complete team of endocrinologists, neurosurgeons, radiologists and radiotherapists.

Second malignancies after permanent implant prostate cancer brachytherapy: A single-institution study of 675 patients treated between 1999 and 2003.

PURPOSE: To analyse the rate of secondary malignancies observed in a series of 675 prostate cancer patients who underwent a permanent implant brachytherapy between 1999 and 2003, and to compare the incidence with the expected rate in a matched general French population. MATERIAL AND METHODS: The cohort included low-risk patients and a selection of "favourable-intermediate" risk patients. All patients were homogeneously treated using an intraoperative dynamic planning prostate brachytherapy technique, with loose 125-iodine seeds and a prescription dose of 145Gy. The mean follow-up was 132 months. RESULTS: The 10-year overall survival for the entire cohort was 92% (95% confidence interval [CI]: 90-94). The 10-year relapse-free survival rate was 82% (95% CI: 79-85). Overall, 61 second cancers were registered. When comparing with a matched general French population, the standard incidence ratio (SIR) for bladder cancer was 1.02 (95% CI: 0.46-1.93). For colorectal cancer, the SIR was 0.45 (95% CI: 0.19-0.89). For lung cancer, the SIR was 0.38 (95% CI: 0.17-0.76). The SIR for all cancers was 0.61 (95% CI: 0.47-0.79). When excluding secondary colorectal and lung cancers (both with low SIRs in this series), the SIR for all cancers was 1.06 (95% CI: 0.77-1.29). CONCLUSION: With a mean follow-up of more than 11 years, this series does not detect any excess risk of second cancers associated with permanent implant prostate brachytherapy. However, due to power limitation, a small increase in the risk of secondary malignancies cannot be totally ruled out.

Long-term results of permanent implant prostate cancer brachytherapy: A single-institution study of 675 patients treated between 1999 and 2003.

PURPOSE: To analyse long-term overall survival, relapse-free survival and late toxicities in a series of 675 patients treated between 1999 and 2003, with a median follow-up of 132 months. PATIENTS AND METHODS: The cohort included low-risk patients and a selection of "favourable-intermediate" risk patients. All patients were homogeneously treated using an intraoperative dynamic planning prostate brachytherapy technique, with loose 125 iodine seeds. Hormone therapy, consisting most often of an anti-androgen alone, was given in 393 patients (58%). RESULTS: The 10-year overall survival was 92% (95% confidence interval [CI]: 90-94) without a significant difference between the low and the select intermediate-risk groups (P=0.17). The 10-year relapse-free survival rate for the entire cohort was 82% (95% CI: 79-85), and was significantly higher in the low-risk group than in the intermediate one (87 vs 71%; P<0.0001). Twenty-six percent of the relapses observed in this series occurred after more than 10 years of follow-up. The 10-year cumulative incidence of grade 3-4 urinary toxicity (whatever the delay and the recovery) was 5.78%. The cumulative incidence of grades 3-4 rectal toxicity in the present series was 1.65% at 10 years. As for sexual toxicity, 61% of our patients retained an erectile capacity at 10 years (with or without oral medication), with age being a major factor. CONCLUSION: With a median follow-up of more than 11 years, this series appears to confirm the excellent long-term results of low-dose rate prostate brachytherapy, both in terms of survival and in terms of toxicity.

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.

Impact of neck node radioresponsiveness on the regional control probability in patients with oropharynx and pharyngolarynx cancers managed by definitive radiotherapy.

We reviewed a series of 1,666 patients with squamous cell carcinoma of the oropharynx and pharyngolarynx treated with definitive radiation therapy to determine whether or not radioresponsiveness of the metastatic neck nodes is a reliable indicator of their radiocurability. In a determined group of 708 patients with clinically positive neck nodes, only one third of the adenopathies (247/759) completely regressed at the completion of the treatment. At 6 months, only ten percent of the nodes remained palpable. Lymph node clearance rates and halving diameter times were tumor size-dependent. Node clearance rate was also influenced by the site of the primary lesion. The impact of various parameters, both intrinsic and extrinsic to the tumor behavior, is discussed. Neck control probability was significantly higher for complete responders. In this group, the ultimate node control was as good for adenopathies larger than 6 cm as for the smaller ones. Tumor control probability directly related to clearance rate following radiotherapy. Finally, therapeutic implications are derived for nodal dose adjustments and optimal applicability of radiosurgical combinations.

Primary radiotherapy of squamous cell carcinoma of the oropharynx and pharyngolarynx: tentative multivariate modelling system to predict the radiocurability of neck nodes.

In a series of 1251 cases of squamous cell carcinomas of oropharynx and pharyngolarynx with clinically positive neck and treated primarily by radiation therapy a determinate group of 798 cases remained eligible for a multivariate analysis of the prognostic factors related to the regional outcome. Node size (p less than 0.0001), node fixity (p = 0.016) and T stage (p = 0.02) were the significant pretreatment factors independently predictive of neck node control. when regarding the treatment modalities in this determinate group of patients who received tumor doses of at least 55 Gy, only the treatment duration was found to be predictive (p = 0.002). Based on these factors, a multivariate model was constructed and tested by estimating the product-limit survival of the various groups of patients. The predictive accuracy of the equation was assessed by the log-rank test significance levels. The model may help to select, in many clinical situations, the appropriate approach of the management of metastatic neck disease, either by definitive radiation therapy or by combined modalities.

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.

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.

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.

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.

Results of irradiation in squamous cell carcinoma of the soft palate and uvula.

Out of a series of 235 patients presenting with tumours of the soft palate at the Institut Curie, between 1958 and 1980, 146 cases were analysed to evaluate the results of radical radiation therapy. Seventy patients (48%) had advanced T3-T4 disease and 40 patients (27%) had clinically involved metastatic nodes. All patients had a minimum follow-up of 5 years. In 103 cases, megavoltage X-ray therapy was employed. For 43 patients, presenting with small or moderately advanced tumours, a combination of megavoltage and intra-oral orthovoltage X-rays was used. The local control rate at 3 years was 92% for T1, 70% for T2, 58% for T3 and 49% for T4 lesions. Nodal failure was seen in 19 patients. In 9 of these, it was not associated with failure at the primary site, 7 out of 9 occurring marginally or outside the treatment portals. Complications were observed in 16 patients, 7 requiring surgery. The crude 3 and 5 year survival rate was 52 and 40%, respectively, and the disease-free survival 59 and 53%.

Conventional megavoltage radiotherapy in the management of malignant epithelial tumours of the parotid gland.

This is an evaluation of definitive conventional megavoltage radiotherapy in a consecutive series of 35 patients presenting malignant epithelial tumours of the parotid gland. In this series, the 5-year actuarial locoregional control rate was 41% with a 5-year crude survival rate of 36%. The results are analyzed according to tumour presentation and tumour doses. Six of 15 patients with tumours larger than 6 cm have had a lasting locoregional control. During the same period 43 other patients received radiotherapy as a post-operative modality. Results obtained in this group confirm the previously published data. While recent studies tend to demonstrate the specific efficacy of high LET radiation in the management of locally advanced salivary gland tumours, radical conventional radiotherapy can still be employed with a curative intent when neutron facilities are not available.

A multivariate primary tumour control analysis in 465 patients treated by radical radiotherapy for cancer of the tonsillar region: clinical and treatment parameters as prognostic factors.

Out of a consecutive series of 698 cases of squamous cell carcinomas of the tonsillar region treated by radical megavoltage radiotherapy, a determinate group of 465 cases remained eligible for a multivariate analysis of the pretreatment features of the disease and treatment-related parameters predictive of lasting control of the disease at the primary site. T-stage and initial site within the tonsillar region, were the significant pretreatment factors. Tumours arising from the glossopalatine sulcus which are characterized by involvement of the tongue, do significantly worse than those arising from other sites within the tonsillar region: i.e. the tonsil itself, posterior pillar and to a lesser extent the anterior pillar. As regards treatment-related parameters in the 465 cases which received tumour doses of at least 55 Gy, only the length of overall treatment time was found to be predictive. Combining both pretreatment and treatment variables, T-stage (p less than 0.0001), overall treatment time (p less than 0.0001) were by decreasing order of significance the predicting factors, followed by initial site (p = 0.006). When present, tumour extension to the anatomical structures anterior to the tonsillar region was also found to be significant (p = 0.05). Based on these factors, a multivariate model was constructed and tested by estimating the product-limit survival of the various categories of patients. Four groups are individualized with 3 years local control rates ranging from 90 to 21%. The predictive accuracy of the model was assessed by log-rank test significance levels. The model may help to select patients for whom conventional radical radiotherapy is inadequate, and combined modality or altered fractionation regimes should be tried particularly for advanced tumours of the glossopalatine sulcus, and any case with significant invasion of the oral cavity.

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.

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.

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.