Is dose escalation achievable for esophageal carcinoma?

AimTo investigate the feasibility of dose escalation using rapid arc (RA) and Helical Tomotherapy (HT) for patients with upper, middle and distal esophageal carcinomas, even for large tumor volumes.BackgroundIn esophageal cancer, for patients with exclusive radio-chemotherapy, local disease control remains poor. Planning study with dose escalation was done for two sophisticated modulated radiotherapy techniques: Rapid arc against Tomotherapy.Materials and methodsSix patients treated with a RA simultaneous integrated boost (SIB) of 60[[ce:hsp sp="0.25"/]]Gy were re-planned for RA and HT techniques with a SIB dose escalated to 70[[ce:hsp sp="0.25"/]]Gy. Dose volume histogram statistics, conformity indices and homogeneity indices were analyzed. For a given set of normal tissue constraints, the capability of each treatment modality to increase the GTV dose to 70[[ce:hsp sp="0.25"/]]Gy was investigated.ResultsEither HT or VMAT may be used to escalate the dose delivered in esophageal tumors while maintaining the spinal cord, lung and heart doses within tolerance. Adequate target coverage was achieved by both techniques. Typically, HT achieved better lung sparing and PTV coverage than did RA.ConclusionsDose escalation for esophageal cancer becomes clinically feasible with the use of RA and HT. This promising result could be explored in a carefully controlled clinical study which considered normal tissue complications and tumor control as endpoints

Nonlinearity in MCF7 Cell Survival Following Exposure to Modulated 6 MV Radiation Fields: Focus on the Dose Gradient Zone

International audienceThe study of cell survival following exposure to nonuniform radiation fields is taking on particular interest because of the increasing evidence of a nonlinear relationship at low doses. We conducted in vitro experiments using the MCF7 breast cancer cell line. A 2.4 × 2.4 cm(2) square area of a T25 flask was irradiated by a Varian Novalis accelerator delivering 6 MV photons. Cell survival inside the irradiation field, in the dose gradient zone and in the peripheral zone, was determined using a clonogenic assay for different radiation doses at the isocenter. Increased cell survival was observed inside the irradiation area for doses of 2, 10, and 20 Gy when nonirradiated cells were present at the periphery, while the cells at the periphery showed decreased survival compared to controls. Increased survival was also observed at the edge of the dose gradient zone for cells receiving 0.02 to 0.01 Gy when compared with cells at the periphery of the same flask, whatever the isocenter dose. These data are the first to report cell survival in the dose gradient zone. Radiotherapists must be aware of this nonlinearity in dose response

Electronic Portal Imaging Devices Using Artificial Neural Networks

International audienceThe aim of this work was to use the Artificial Neural Network (ANN) in External Beam Radiation Therapy (EBRT), especially for pre-treatment patient-specific quality assurance of Conformational Radiation Therapy (CRT) and Intensity-Modulated Radiation Therapy (IMRT) using Electronic Portal Imaging Device (EPID). The EPIDs need frequent calibration and complex setting in order to be used with dedicated dosimetry software. The idea was to create a model with ANN algorithms allowing the reconstruction of the 2D dose distribution comparable with a corresponding Treatment Planning System (TPS) solution. The supervised ANN algorithms work with two phases—learning and recognition. Learning was performed using data sets regarding CRT and IMRT composed of 8 and 11 input/output respectively. To compare ANN predicted and planned results the global gamma index was used, obtaining a γ(2%,2mm)=99.78% and γ(2%,2mm)=99.7%, respectively. This first work showed the capability of ANN to reconstruct the absorbed dose distribution based on EPID signals

Nonlinearity in MCF7 Cell Survival Following Exposure to Modulated 6 MV Radiation Fields

The study of cell survival following exposure to nonuniform radiation fields is taking on particular interest because of the increasing evidence of a nonlinear relationship at low doses. We conducted in vitro experiments using the MCF7 breast cancer cell line. A 2.4 × 2.4 cm 2 square area of a T25 flask was irradiated by a Varian Novalis accelerator delivering 6 MV photons. Cell survival inside the irradiation field, in the dose gradient zone and in the peripheral zone, was determined using a clonogenic assay for different radiation doses at the isocenter. Increased cell survival was observed inside the irradiation area for doses of 2, 10, and 20 Gy when nonirradiated cells were present at the periphery, while the cells at the periphery showed decreased survival compared to controls. Increased survival was also observed at the edge of the dose gradient zone for cells receiving 0.02 to 0.01 Gy when compared with cells at the periphery of the same flask, whatever the isocenter dose. These data are the first to report cell survival in the dose gradient zone. Radiotherapists must be aware of this nonlinearity in dose response

Dose-painting multicenter phase III trial in newly diagnosed glioblastoma: the SPECTRO-GLIO trial comparing arm A standard radiochemotherapy to arm B radiochemotherapy with simultaneous integrated boost guided by MR spectroscopic imaging

Abstract 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

Integration method of 3D MR spectroscopy into treatment planning system for glioblastoma IMRT dose painting with integrated simultaneous boost.

International audienceUNLABELLED: ABSTRACT: BACKGROUND: To integrate 3D MR spectroscopy imaging (MRSI) in the treatment planning system (TPS) for glioblastoma dose painting to guide simultaneous integrated boost (SIB) in intensity-modulated radiation therapy (IMRT). METHODS: For sixteen glioblastoma patients, we have simulated three types of dosimetry plans, one conventional plan of 60-Gy in 3D conformational radiotherapy (3D-CRT), one 60-Gy plan in IMRT and one 72-Gy plan in SIB-IMRT. All sixteen MRSI metabolic maps were integrated into TPS, using normalization with color-space conversion and threshold-based segmentation. The fusion between the metabolic maps and the planning CT scans were assessed. Dosimetry comparisons were performed between the different plans of 60-Gy 3D-CRT, 60-Gy IMRT and 72-Gy SIB-IMRT, the last plan was targeted on MRSI abnormalities and contrast enhancement (CE). RESULTS: Fusion assessment was performed for 160 transformations. It resulted in maximum differences <1.00 mm for translation parameters and ≤1.15° for rotation. Dosimetry plans of 72-Gy SIB-IMRT and 60-Gy IMRT showed a significantly decreased maximum dose to the brainstem (44.00 and 44.30 vs. 57.01 Gy) and decreased high dose-volumes to normal brain (19 and 20 vs. 23% and 7 and 7 vs. 12%) compared to 60-Gy 3D-CRT (p < 0.05). CONCLUSIONS: Delivering standard doses to conventional target and higher doses to new target volumes characterized by MRSI and CE is now possible and does not increase dose to organs at risk. MRSI and CE abnormalities are now integrated for glioblastoma SIB-IMRT, concomitant with temozolomide, in an ongoing multi-institutional phase-III clinical trial. Our method of MR spectroscopy maps integration to TPS is robust and reliable; integration to neuronavigation systems with this method could also improve glioblastoma resection or guide biopsies