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Purpose Proton magnetic resonance spectroscopic imaging (1H MRSI) is a noninvasive technique for assessing tumor metabolism. Manual inspection is still the gold standard for quality control (QC) of spectra, but it is both time-consuming and subjective. The aim of the present study was to assess automatic QC of glioblastoma MRSI data using random forest analysis. Methods Data for 25 patients, acquired prospectively in a preradiotherapy examination, were submitted to postprocessing with syngo.MR Spectro (VB40A; Siemens) or Java-based magnetic resonance user interface (jMRUI) software. A total of 28 features were extracted from each spectrum for the automatic QC. Three spectroscopists also performed manual inspections, labeling each spectrum as good or poor quality. All statistical analyses, with addressing unbalanced data, were conducted with R 3.6.1 (R Foundation for Statistical Computing; https://www.r-project.org). Results The random forest method classified the spectra with an area under the curve of 95.5%, sensitivity of 95.8%, and specificity of 81.7%. The most important feature for the classification was Residuum_Lipids_Versus_Fit, obtained with syngo.MR Spectro. Conclusion The automatic QC method was able to distinguish between good- and poor-quality spectra, and can be used by radiation oncologists who are not spectroscopy experts. This study revealed a novel set of MRSI signal features that are closely correlated with spectral quality.

Background Glioblastoma, a high-grade glial infiltrating tumor, is the most frequent malignant brain tumor in adults and carries a dismal prognosis. External beam radiotherapy (EBRT) increases overall survival but this is still low due to local relapses, mostly occurring in the irradiation field. As the ratio of spectra of choline/N acetyl aspartate> 2 (CNR2) on MR spectroscopic imaging has been described as predictive for the site of local relapse, we hypothesized that dose escalation on these regions would increase local control and hence global survival. Methods/design In this multicenter prospective phase III trial for newly diagnosed glioblastoma, 220 patients having undergone biopsy or surgery are planned for randomization to two arms. Arm A is the Stupp protocol (EBRT 60 Gy on contrast enhancement + 2 cm margin with concomitant temozolomide (TMZ) and 6 months of TMZ maintenance); Arm B is the same treatment with an additional simultaneous integrated boost of intensity-modulated radiotherapy (IMRT) of 72Gy/2.4Gy delivered on the MR spectroscopic imaging metabolic volumes of CHO/NAA > 2 and contrast-enhancing lesions or resection cavity. Stratification is performed on surgical and MGMT status. Discussion This is a dose-painting trial, i.e. delivery of heterogeneous dose guided by metabolic imaging. The principal endpoint is overall survival. An online prospective quality control of volumes and dose is performed in the experimental arm. The study will yield a large amount of longitudinal multimodal MR imaging data including planning CT, radiotherapy dosimetry, MR spectroscopic, diffusion and perfusion imaging. Trial registration NCT01507506, registration date December 20, 2011.

Optimal doses of total skin electron beam therapy for mycosis fungoides remain to be established. Clinical efficiency and adverse effects of middle-dose (25 Gy) vs. low-dose (10-12 Gy) total skin electron beam therapy were retrospectively compared in a series of 14 and 12 mycosis fungoides, respectively. Overall skin response rate was 96.2% (92.9% middle-dose and 100% low-dose; not significant (NS)). Overall complete and partial skin response rates were 57.7% (42.9% middle-dose and 75% low-dose; NS) and 38.5% (50% middle-dose and 25% low-dose; NS), respectively. All responding patients relapsed after an overall median time of 5 months (7 months middle-dose vs. 4 months low-dose; p = 0.164, NS). Tolerance was equally fair in both groups, with only grade 1 and 2 adverse events observed in 100% vs. 66.7% of patients in middle-dose and low-dose groups (NS). Although no significant difference was observed, middle-dose protocol may be recommended owing to a longer relapse-free survival for a similar tolerance.

Background Glioblastoma is the most frequent primary malignant brain tumor. In daily practice and at whole country level, oncological care management for glioblastoma patients is not completely known. Objectives To describe oncological patterns of care, prognostic factors, and survival for all patients in France with newly-diagnosed and histologically confirmed glioblastoma, and evaluate the impact of extended temozolomide use at the population level. Methods Nationwide population-based cohort study including all patients with newly-diagnosed and histologically confirmed glioblastoma in France in 2008 and followed until 2015. Results Data from 2053 glioblastoma patients were analyzed (male/female ratio 1.5, median age 64 years). Median overall survival (OS) was 11.2 [95% confidence interval (CI) 10.7–11.9] months. The first-line therapy and corresponding median survival (MS, in months) were: 13% did not receive any oncological treatment (biopsy only) (MS = 1.8, 95% CI 1.6–2.1), 27% received treatment without the combination of radiotherapy (RT)–temozolomide (MS = 5.9, 95% CI 5.5–6.6), 60% received treatment including the initiation of the concomitant phase of RT–temozolomide (MS = 16.4, 95% CI 15.2–17.4) whom 44% of patients initiated the temozolomide adjuvant phase (MS = 18.9, 95% CI 18.0–19.8). Only 22% patients received 6 cycles or more of adjuvant temozolomide (MS = 25.5, 95% CI 24.0–28.3). The multivariate analysis showed that the risk of mortality was significantly higher for the non-progressive patients who stopped at 6 cycles (standard protocol) than those who continued the treatment, hazard ratio = 1.5 (95% CI 1.2–1.9). Conclusion In non-progressive patients, prolonging the adjuvant temozolomide beyond 6 cycles may improve OS. Electronic supplementary material The online version of this article (10.1007/s11060-018-03065-z) contains supplementary material, which is available to authorized users.

Introduction et but de l’etude Le traitement standard des recidives intraprostatiques isolees repose sur l’hormonotherapie. La prise en charge locale est discutee et souvent morbide. La reirradiation est une technique attrayante mais expose a un risque eleve de toxicite. La radiotherapie guidee par l’IRM permet d’obtenir des niveaux de doses eleves au niveau tumoral tout en diminuant les doses aux organes a risque. Le but de cette etude etait d’evaluer la toxicite aigue d’une reirradiation avec le systeme MRIdian® (ViewRay® Technologies, Inc.). Materiel et methodes Vingt patients pris en charge consecutivement a l’Institut du cancer de Montpellier (ICM) pour une recidive isolee intraprostatique prouvee d’un adenocarcinome de prostate entre le 21/10/2019 et le 13/03/2020 ont ete inclus. L’âge moyen des patients etait de 76 ans avec un indice de performance selon l’Organisation mondiale de la sante (OMS) de 0 ou 1. La concentration serique moyenne d’antigene specifique de la prostate avant la reirradiation etait de 6,45 μg/mL et l’International Prostate Symptom Score (IPSS) moyen de 8. L’intervalle moyen entre les deux irradiations etait de 9,9 ans. Quatre patients (soit 20 %) ont recu une hormonotherapie en concomitance. La radiotherapie etait adaptative pour sept patients (35 %). La dose prescrite etait de 30 Gy en cinq fractions pour 12 patients, 27,5 Gy en cinq fractions pour cinq patients, 30 Gy en six fractions pour deux patients et 38,7 Gy en neuf fractions pour un patient. Tous les patients ont ete revus en fin d’irradiation et 19 patients sur 20 a 6 semaines apres l’irradiation. Resultats et analyse statistique Les donnees de toxicite urinaire et rectale sont donnees dans le Tableau 1 . Seuls deux patients (10 %) ont vu une modification de l’IPSS entre le debut et la fin de l’irradiation avec un maximum de variation du score de 3 sur 35. Les profils de toxicite urinaire et digestive etaient semblables avant l’irradiation, en fin d’irradiation, et six semaines apres. Aucun patient n’a souffert de toxicite de grade superieur a 2. Pour tous les patients dont la concentration serique d’antigene specifique de la prostate a ete redosee six semaines apres la fin de l’irradiation (soit huit patients), une diminution a ete constatee avec une concentration moyenne avant l’irradiation de 5,95 μg/mL (extremes : 0,34–14,73 μg/mL) contre 3,63 (extremes : 0,08–13,09 μg/mL) a six semaines. Conclusion La reirradiation guidee par IRM des recidives intraprostatiques ne semble pas engendrer de toxicite aigue importante. Un recul plus important nous permettra d’evaluer la toxicite tardive et le benefice clinique.

To assess the value of T2* dynamic-susceptibility contrast MRI (DSC-MRI) and diffusion-weighted imaging (DWI) to predict the glioblastoma relapse sites after chemoradiation. From a cohort of 44 patients, primarily treated with radiotherapy (60 Gy) and concomitant temozolomide for glioblastoma, who were included in the reference arm of a prospective clinical trial (NCT01507506), 15 patients relapsed and their imaging data were analyzed. All patients underwent anatomical MRI, DSC-MRI and DWI before radiotherapy and every 2 months thereafter until relapse. Voxels within the sites of relapse were correlated with their perfusion and/or diffusion abnormality (PDA) pretreatment status after rigid co-registration. The relative cerebral blood volume (rCBV) and apparent diffusion coefficient (ADC) were used as biomarkers. Several PDA areas were thresholded: hyperperfused voxels using a 1.75 fixed rCBV threshold (HPt); hypoperfused (hPg) and hyperperfused (HPg) voxels using a histogram-based Gaussian method; diffusion-restricted voxels (DRg); and HPg voxels with diffusion restriction (HPg&DRg). Two sets of voxels (2,459,483 and 2,073,880) were analyzed according to these thresholding methods. Positive predictive values (PPV) of PDA voxels were low (between 9.5 and 31.9 %). The best PPV was obtained with HPg&DRg voxels within the FLAIR hyperintensity, as 18.3 % of voxels without initial PDA were within relapse sites, versus 31.9 % with initial PDA (p

Background Glioblastomas (GBMs) induce a peritumoural vasogenic oedema impairing functional status and quality of life. Steroids reduce brain tumour–related oedema but are associated with numerous side-effects. It was reported in a retrospective series that angiotensin receptor blockers might be associated with reduced peritumoural oedema. The ASTER study is a randomised, placebo-controlled trial to assess whether or not the addition of Losartan to standard of care (SOC) can reduce steroid requirement during radiotherapy (RT) in patients with newly diagnosed GBM. Patients and methods Patients with a histologically confirmed GBM after biopsy or partial surgical resection were randomised between Losartan or placebo in addition to SOC with RT and temozolomide (TMZ). The primary objective was to investigate the steroid dosage required to control brain oedema on the last day of RT in each arm. The secondary outcomes were steroids dosage 1 month after the end of RT, assessment of cerebral oedema on magnetic resonance imaging, tolerance and survival. Results Seventy-five patients were randomly assigned to receive Losartan (37 patients) or placebo (38 patients). No difference in the steroid dosage required to control brain oedema on the last day of RT, or one month after completion of RT, was seen between both arms. The incidence of adverse events was similar in both arms. Median overall survival was similar in both arms. Conclusions Losartan, although well tolerated, does not reduce the steroid requirement in newly diagnosed GBM patients treated with concomitant RT and TMZ. Trial registration number NCT01805453 with ClinicalTrials.gov.

Resume Nous proposons dans cette revue de rapporter l’impact de la radiotherapie stereotaxique chez les patients ayant un cancer oligometastatique ou en oligoprogression en termes de survie sans progression metastatique et globale, et d’identifier quelle est la place de cette modalite de radiotherapie au sein du parcours–patient.

Palliative radiation therapy is well-known in the setting of metastatic lesions (haemostatic, analgesic, anti-inflammatory aims, etc.). Palliative primary tumour radiotherapy is less studied. Here we propose a review of palliative indications of primary tumours, the most studied in the literature, and their radiotherapy modalities (target volumes and fractionation).

Breast cancers are highly radiosensitive since the risk of recurrences and of mortality after adjuvant radiotherapy following breast-conserving surgery is decreased by 15.7% and 3.8%, respectively at 10 years. The total dose if irradiation also significantly increases local control: a boost of 16 Gy to the tumour bed after breast-conserving surgery reduces the absolute risk of recurrence by 4% at 10 years. Breast cancers are sensitive to the dose per fraction, as shown by the results from four randomized trials which compared standard irradiation (50 Gy/25 fractions) with a hypofractionated scheme: no statistical difference was observed in locoregional recurrence and overall survival at 10 years. The α/β ratio, which reflects the dose per fraction and is theoretically over 10 Gy for tumour tissues, has been estimated between 2.2 and 4.4 Gy for breast cancers. Molecular abnormalities, such as overexpression of HER1 (especially in triple negative breast cancer) and HER2, induce a higher radioresistance. In vitro studies showed that targeted therapies, which block these receptors, increase breast cancer radiosensitivity. Tumour stem cells have been identified in breast cancers and are characterized by a higher radioresistance. This radioresistance could be related to a better repair of radiation-induced DNA damages and a decrease of reactive oxygen species (ROS), which are involved in their occurrence. In the future, a better understanding of genetics tumour abnormalities will allow to identify new radiosensitivity settings in breast cancers.

Resume Le traitement en un jour du cancer du sein se definit par l’association d’une chirurgie ambulatoire et d’une irradiation peroperatoire. La selection des patientes et des tumeurs associees a la rigueur du parcours patient assurent son succes. La technique operatoire n’est pas modifiee par l’irradiation peroperatoire. L’evaluation de l’indice de satisfaction des patientes est tres elevee. La moins value financiere actuelle de cette association therapeutique ne doit pas etre un frein a sa mise en place.

BACKGROUND: Glioblastomas, the most common primary central nervous system tumors, induce a peritumoral vasogenic edema impairing functional status and quality of life. Steroids reduce brain tumor-related edema, but are associated with numerous side effects. It was reported in a retrospective series that angiotensin receptor blockers (ARBs) might be associated with reduced peritumoral edema. The ASTER study is a randomized, placebo-controlled trial to assess whether or not the addition of Losartan to standard of care can reduce steroid requirement during radiotherapy in patients with newly diagnosed glioblastoma. MATERIAL AND METHODS: Patients with a histologically confirmed newly diagnosed glioblastoma after biopsy or partial surgical resection were randomized between Losartan or placebo in addition to standard of care (SOC) with radiotherapy (RT) and temozolomide (TMZ). The primary objective was to investigate the steroid dosage required to control brain edema on the last day of RT in each arm. The secondary outcomes were steroids dosage 1 month after the end of RT, assessment of cerebral edema on MRI, tolerance, and survival. RESULTS: Seventy five (75) patients were randomly assigned to receive Losartan (37 patients) or placebo (38 patients). No difference in the steroid dosage required to control brain edema on the last day of radiotherapy, or one month after completion of RT, was seen between both arms. A trend towards reduction of peritumoral edema over time was seen on MRI, but this reduction did not reach statistical significance. Median OS was similar in both arms. CONCLUSION: Losartan, although well tolerated, does not reduce the steroid requirement in newly diagnosed GBM patients treated with concomitant radiotherapy and temozolomide.

International audience; Irradiation techniques for breast cancer (arctherapy, tomotherapy) are evolving and intensity-modulated radiation therapy is being increasingly considered for the management of these tumours. Here, we propose a review of intensity-modulated radiation therapy planning issues, clinical toxicities and indications for breast cancer.

International audience; Surgery (radical cystectomy) is the standard treatment of muscle-invasive bladder cancer. Radiochemotherapy has risen as an alternative treatment option to surgery as part as organ-sparing combined modality treatment or for patients unfit for surgery. Radiochemotherapy achieves 5-year bladder intact survival of 40 to 65% and 5-year overall survival of 40 to 50% with excellent quality of life. This article introduces the French recommendations for radiotherapy of bladder cancer: indications, exams, technique, dosimetry, delivery and image guidance.

International audience; The aim was to analyze arc therapy techniques according to the number and position of the brain lesions reported by comparing dynamic noncoplanar conformal arcs (DCA), two coplanar full arcs (RAC) with volumetric-modulated arc therapy (VMAT), multiple noncoplanar partial arcs with VMAT (RANC), and two full arcs with VMAT and 10° table rotation (RAT). Patients with a single lesion (n= 10), multiple lesions (n = 10) or a single lesion close to organs at risk (n = 5) and previously treated with DCA were selected. For each patient, the DCA treatment was replanned with all VMAT techniques. All DCA plans were compared with VMAT plans and evaluated in regard to the different quality indices and dosimetric parameters. For single lesion, homogeneity index (HI) better results were found for the RANC technique (0.17 ± 0.05) compared with DCA procedure (0.27± 0.05). Concerning conformity index (CI), the RAT technique gave higher and better values (0.85 ± 0.04) compared with those obtained with the DCA technique (0.77 ± 0.05). DCA improved healthy brain protection (8.35 ± 5.61 cc vs. 10.52 ± 6.40 cc for RANC) and reduced monitor unit numbers (3046 ± 374 MU vs. 4651 ± 736 for RANC), even if global room occupation was higher. For multiple lesions, VMAT techniques provided better HI (0.16) than DCA (0.24 ± 0.07). The CI was improved with RAT (0.8 ± 0.08 for RAT vs. 0.71 ± 0.08 for DCA). The V10Gy healthy brain was better protected with DCA (9.27 ± 4.57 cc). Regarding the MU numbers: RANC < RAT< RAC < DCA. For a single lesion close to OAR, RAT achieved high degrees of homogeneity (0.27 ± 0.03 vs. 0.53 ± 0.2 for DCA) and conformity (0.72± 0.06vs. 0.56 ± 0.13 for DCA) while sparing organs at risk (Dmax = 12.36 ± 1.05Gyvs. 14.12 ± 0.59 Gy for DCA, and Dmean = 3.96 ± 3.57Gyvs. 4.72 ± 3.28Gy for DCA). On the other hand, MU numbers were lower with DCA (2254 ± 190 MUvs. 3438 ± 457 MU for RANC) even if overall time was inferior with RAC. For a single lesion, DCA provide better plan considering low doses to healthy brain even if quality indexes are better for the others techniques. For multiple lesions, RANC seems to be the best compromise, due to the ability to deliver a good conformity and homogeneity plan while sparing healthy brain tissue. For a single lesion close to organs at risk, RAT is the most appropriate technique.

International audience; BACKGROUND:Accelerated partial breast irradiation (APBI) is an option for adjuvant radiotherapy according to ASTRO and ESTRO recommendations. Among the available techniques, volumetric-modulated arc therapy (VMAT) is attractive but has not been extensively studied for APBI. This study assessed its feasibility, tolerance and early oncological outcomes.METHODS:We analysed the data of nine patients (median age 74 years) with ten lesions (one bilateral cancer) treated from May 2011 to July 2012 with APBI using VMAT. The radiation oncologist delineated the surgical tumour bed, and added an 18 mm isotropic margin to obtain the planning target volume (PTV). The dose was 40 Gy prescribed in 4 Gy fractions given twice a day over five days. Patients were regularly followed for toxicities and oncological outcomes.RESULTS:Mean PTV was 100.0 cm(3) and 95 % of the PTV received a mean dose of 99.7 % of the prescribed dose. Hot spots represented 0.3 % of the PTV. 6.2 %, 1.6 % and 0.3 % of the ipsilateral lung volume received 5 Gy (V5Gy), 10 Gy (V10Gy) and 20 Gy (V20Gy), respectively. Regarding the contralateral lung, V5Gy was 0.3 %, and V10Gy and V20Gy were nil. V5Gy accounted for 3.1 % of the heart. An average 580 monitor units were delivered. No acute or late grade ≥ 2 toxicities were observed. With a median follow-up of 26 months, no relapses occurred.CONCLUSION:In our study, VMAT allowed optimal dosimetry with consequential high therapeutic ratio in elderly and frail patients.

International audience; To identify relevant relative cerebral blood volume biomarkers from T2* dynamic-susceptibility contrast magnetic resonance imaging to anticipate glioblastoma progression after chemoradiation. Twenty-five patients from a prospective study with glioblastoma, primarily treated by chemoradiation, were included. According to the last follow-up MRI confirmed status, patients were divided into: relapse group (n = 13) and control group (n = 12). The time of last MR acquisition was t(end); MR acquisitions performed at t(end-2M), t(end-4M) and t(end-6M) (respectively 2, 4 and 6 months before t(end)) were analyzed to extract relevant variations among eleven perfusion biomarkers (B). These variations were assessed through R(B), as the absolute value of the ratio between a dagger B from t(end-4M) to t(end-2M) and a dagger B from t(end-6M) to t(end-4M). The optimal cut-off for R(B) was determined using receiver-operating-characteristic curve analysis. The fraction of hypoperfused tumor volume (F_hP(g)) was a relevant biomarker. A ratio R(F_hP(g)) aeyenaEuroe0.61 would have been able to anticipate relapse at the next follow-up with a sensitivity/specificity/accuracy of 92.3 %/63.6 %/79.2 %. High R(F_hPg) (aeyen0.61) was associated with more relapse at t(end) compared to low R(F_hPg) (75 % vs 12.5 %, p = 0.008). Iterative analysis of F_hP(g) from consecutive examinations could provide surrogate markers to predict progression at the next follow-up. aEuro cent Related rCBV biomarkers from DSC were assessed to anticipate GBM progression. aEuro cent Biomarkers were assessed through their patterns of variation during the follow-up. aEuro cent The fraction of hypoperfused tumour volume (F_hP (g) ) seemed to be a relevant biomarker. aEuro cent An innovative ratio R(F_hP (g) ) could be an early surrogate marker of relapse. aEuro cent A significant time gain could be achieved in the management of GBM patients.

In the era of high-tech radiotherapy, hypofractionated schema is more and more widely used regardless of tumour sites. In this article, we expose the role, techniques and indications of hypofractionated radiotherapy in adjuvant breast radiotherapy.

One-day breast carcinoma treatment is defined as association of ambulatory surgery and intra-operative irradiation. Selection and rigorous process of patients is the key to success. The surgical technique is not changed by the radiotherapy. Patient's satisfaction index is very high. Financial loss should not be a hurdle to its implementation.

e13005 Background: This work describes oncological patterns of care and survival for all patients (pts) with newly diagnosed histologically confirmed glioblastoma (GB) in metropolitan France in 200...

e13051 Background: National brain tumor registries exist only in few countries, and systematic brain tumor declaration is not mandatory in many countries. Here we propose an easy method to build a ...

Introduction In order to select the best one according to the number and the position of the lesions we compare in this study dynamic conformal arc (DCA), coplanar VMAT (RAC), noncoplanar VMAT (RANC) and entire arc VMAT with table rotations of 10° and 350° (RAT). Material and methods 5 single lesions (case 1), 5 multiple lesions (case 2) and 5 single lesions close to organs at risk (case 3) were analyzed. Each technique was evaluated in regard to conformity and homogeneity indexes for PTV (CI = [[(PTV covered by prescription isodose)tˆ2/(V*PTV*V_(prescription isodose)) and HI=(D_max- D_min)/D_mean), the healthy brain tissue dose (V10Gy), Dmax (OAR) and the number of monitor units (MU). Results For case 1, HI and CI are better for RANC (HI: 0.17 RANC – 0.22 RAT – 0.23 RAC _0.27 DCA and CI: 0.86 RAT – 0.85 RANC _0.83 RAC – 0.76 DCA) but DCA reduces brain tissue V10Gy (11.97 cc DCA – 14.51 cc RANC – 15.9 cc RAT – 18.34 cc RAC) and MU (3092 DCA – 4573 RAC – 4639 RANC – 5250 RAT). In case 2, HI is similar for VMAT (0.17 RANC and RAT – 0.18 RAC – 0.22 DCA) and CI is top with RAT (0.72 RAT – 0.68 RAC – 0.67 RANC – 0.65 DCA). The healthy brain is as well protected with DCA as with RANC (10.5 DCA and RANC – 15.08 RAT – 18.12 RAC) but MU decrease with RANC (4250 RANC – 4802 RAT – 4841 RAC – 7908 DCA). For case 3, RAT improves HI and CI (HI: 0.27 RAT – 0.3 RANC – 0.31 RAC – 0.57DCA and CI: 0.74 RAT – 0.65 RAC – 0.59 RANC _0.5 DCA) and spares brain tissue and OAR (V10Gy: 1.31 RAT – 1.56 RAC – 2 RANC – 2.31 DCA and Dmax (OAR): 12.17 RAT – 12.59 RAC – 12.77 RANC – 14.15 Gy DCA). The MU numbers decrease with DCA (2184 DCA – 3533 RANC – 3714 RAT – 3840 RAC). Conclusion For simple case 1, DCA provide better plan considering low doses to healthy brain. For case 2, RANC is the best compromise ‘‘PTV cover- brain protection”. For case 3, results are significantly better with RAT.

blocks, which could open the way to improved CTV definition and planning. Materials/Methods: An in-house, spectral domain OCT system was developed for this study. A pair of tilting galvanometer mirrors permits lateral scanning of the infrared beam resulting in a 5x5x3-mm image volume. Paraffin blocks (40x25x4 mm) containing formalin-fixed mouse mammary glands with tumor were imaged. Other than removing the plastic mount, the blocks were not manipulated in any way in preparation for imaging. After each scan, the blockswere translated on amoveable stage until the entire samplewas imaged. Blocks were scanned through both sides in order to image their full thickness. Individual scans were stitched together to generate a final, complete image volume. For comparison, sections at multiple depths were obtained from the blocks, stained with hematoxylin and eosin (H&E), and photographed at high magnification and resolution. Results: Complete 3D images of the tissue blocks were obtained. The scan time for a single 5x5x3-mm image was about 15 seconds. A lateral resolution of 16 mm and a 6-mm resolution in the depth direction permitted visualization of tissue micro-architecture that correlated with the H&E section images. Images from consecutive blocks could be stitched together, allowing reconstruction of larger specimens over multiple blocks. Because of the paraffin medium, both micro-CT and small animal MRI were unable to visualize any features within the blocks. Conclusions: Optical coherence tomography is a fast, non-invasive, highresolution imaging modality capable of volumetric reconstruction of paraffin tissue blocks. As such, it could greatly facilitate the imaging and analysis of microscopic disease needed to study and improve CTV design and treatment. Author Disclosure: L. Kim: None. R. Droz-Rosario: None. E. Hwuang: None. L. Higgins: None. M. Pierce: None.

105 Background: Thirteen hundred prostate cancer patients have been treated with Intensity modulated radiotherapy (IMRT) since 2001. We present the final results of the pilot study concerning the first 373 patients with a median follow-up of 72.7 months (range 0 to 130). Methods: All patients received the entire treatment course to a prescribed total dose of 80 Gy. No pelvic irradiation was applied. Androgen ablation therapy was delivered for 6 months and 2 to 3 years in intermediate and high-risk patients, respectively (n=142, 38%). Prostate-specific antigen (PSA) failure was defined as nadir + 2. Toxicity was assessed according to the National Cancer Institute (NCI)/Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Multivariate analysis using the Cox model was performed to assess factors that may impact on PSA relapse. Logistic regression was used to correlate clinical and physical parameters with grade 2 or higher gastro-intestinal and genitourinary toxicities. Results: Median age was 69 (range 40 to 81). One hundred thirty nine (37.3%), 167 (44.8%), and 67 (18%) patients were classified as low (group 1), intermediate (group 2), and high-risk (group 3) patients, respectively. The 5 year biochemical relapse-free survival (5y-biochemical recurrence-free survival [bRFS]) was 85.7% (95% CI, 0.81-0.89). For the three prognostic groups, 5y-bRFS was 91% (95% CI, 0.85-0.95), 82% (95% CI, 0.75-0.87), and 80% (95% CI, 0.67-0.88) for groups 1, 2, and 3, respectively. Multivariate analysis showed that the absence of hormonotherapy in the group 2 and the number of positive biopsies impact on PSA relapse (p=0.04, HR 1.8 and p=0.01, HR 2.13, respectively). The incidence of late grade 2 or higher rectal and urinary toxicities were 10.5% and 12.7%, respectively. The dose received by 50% (D50) of the rectum was the only factor significantly correlated with late grade 2 or higher rectal toxicities (p = 0.04). Similarly, the dose received by 50% (D50) of the bladder was the only factor significantly correlated with late grade 2 or higher bladder side-effects (p = 0.02). Conclusions: IMRT to 80 Gy can provide good to excellent carcinologic results and low late toxicity rates in all prostate cancer subgroups. Hormonotherapy combined to high dose IMRT seems to be a serious option to consider in intermediate-risk patients. Clinical trial information: ICM 2001-13.

150 Background: Everolimus is able to stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving everolimus together with hormonotherapy and radiation therapy may kill more tumor cells. Methods: We conducted a phase I trial to evaluate the impact of everolimus (RAD001), an mTOR inhibitor, in patients treated concurrently with radiotherapy (RT) and ablative androgen treatment in high-risk locally advanced prostate cancer. Inclusion criteria were high-risk locally advanced non metastatic prostate cancer defined as clinical stage ≥ T3 or Gleason score ≥ 8 or PSA ≥ 20. The week before the beginning of RT, RAD001 was administered at different dose levels, twice daily, until the last day of irradiation. A nonsteroid antiandrogen was also given for 1 month at the beginning of RT. Prostate and seminal vesicle were irradiated up to 74Gy in 37 fractions of 2Gy with concomitant long-term LHRH analogue. The starting dose of RAD001 was 5mg/d with subsequent dose levels of 7.5 and 10 mg/d. The primary endpoint was the determination of the maximum tolerated dose (MTD). Dose escalation was implemented according to the continual reassessment method (CRM). Results: Fifteen patients were enrolled and 14 were assessable for toxicity and response. Significant toxicities were demonstrated at the 7.5 and 10 mg/d dose levels. Dose-limiting toxicity (DLT) occurred in two patients at dose level 7.5 mg/d and characterized by a grade 3 diarrhea and a grade 3 hydronephrosis due to dehydration and kidney lithiasis. DLT also occurred in two patients at dose level 10 mg/d (grade 3 diarrhea and grade 3 laryngopharyngeal infection). The MTD was reached at 7.5 mg/day (dose-level II). The recommended dose of RAD001 was 5 mg/d. After a median follow-up of 22 months, 12 patients are alive, 1 is dead (not related to cancer) and 2 patients had relapsed. Conclusions: Concomitant hormone-radiotherapy and everolimus is well-tolerated with mucositis, hypercholesterolemia, and urinary disorders. The recommended phase-II trial dose of everolimus in this combined setting is 5 mg/day. Clinical trial information: NCT00943956.