T.S. Hong

TH‐E‐218‐08: In‐Vivo Dosimetric Verification of Hypo‐Fractionated Proton Radiation Therapy of the Liver with Hepatocyte‐Specific Functional MRI

Purpose: To investigate if MRI of the liver can be used for in‐vivo dose verification in proton therapy. Recently it was shown that irradiated healthy livertissue shows a strong systematic decrease in uptake of a hepatobiliary‐directed contrast agent (Gd‐EOB‐DTPA) six weeks after brachytherapy. In this study it is investigated, if the radiation‐related effect is also detectable for hypo‐fractionated proton therapy. Methods: For patients who receive liver lesion directed hypo‐fractionated proton therapy (5 fractions within 2 weeks) Gd‐EOB‐DTPA enhanced MRI is performed 10–12 weeks after treatment. MR images are registered to the planning CT and the planned dose map by non‐rigid image registration. The reviewer contours the border of hypointensity on T1‐w images that indicates the hepatocyte function loss. The threshold dose for this function loss is evaluated as the D90, the dose achieved in at least 90% of the pseudolesion volume. Moreover, irradiated‐ to‐non‐irradiated livercontrast and the correlation of detected signal change in MRI with the planned dose map are analyzed. Results: Gd‐EOB‐DTPA enhanced T1‐w MR images taken after hypo‐fractionated proton therapy show a hypo‐intense area that is correlated to the area of high dose deposition in shape and volume with small deviations in location (up to 5–6 mm) giving information on the actual distal edge position. With Gd‐EOB‐DTPA enhanced MRI, irradiated‐to‐non‐irradiated contrast is superior to MRI enhanced with extracellular, nonspecific contrast agents used in a previous study. Conclusions: A biomarker for radiation induced changes in livertissue was identified and promising post‐treatment MRI data have been acquired and are currently evaluated. For the next step, a pilot patient study has been set up to investigate, if radiation‐induced changes using Gd‐EOB‐DTPA enhanced MRI can be detected prospectively during fractionated proton therapy and therefore would allow for an immediate assessment of the proton therapy with direct impact on patient safety. The work was partly supported by the German Federal Ministry of Education and Research (BMBF) under contract no. 03ZIK445.

SU‐C‐110‐05: Analysis of Intra‐ and Inter‐Fractional Range Variations to Fiducials in Proton Radiotherapy of Liver Tumors

Purpose: To quantify radiological pathlength variations to fiducials in proton beam treatment of livertumors. Methods: Serial 4DCT scans of 10 patients with primary livertumors were analyzed. The water equivalent pathlength (WEL) was quantified from entrance surface to radio‐opaque clips 1) for different respiratory phases 2) for serial 4DCT scans 3) for each treatment angle (typically AP or PA and a single lateral field) 4) for different immobilization methods. WEL measurements to fiducials is well defined, Vs range to the distal surface of a deformably registered target, but results in fewer measurements (typically 3 clips). A statistical analysis of the mean range variations and spread is performed. Results: AP range at T50 to clips is reproducible from day to day with a mean variation of 1.8mm, SD 1.3mm. Lateral field range variations from day to day at T50 were 1.3mm SD 2.6mm. Range variations at inhale were more variable, with AP T00 mean WEL variation of 3.5mm SD 4.4mm and lateral mean variations of 3.2mm SD 1.7mm. An 8mm lateral range variation was observed in one patient. Range variation during respiration was also studied. The mean AP and lateral range variation was 3mm SD 2.4 and 4.1 mm SD 2.1mm. A 13mm variation was observed in one patient, and attributed to clip motion during respiration without significant change in the entrance surface. Conclusions: Several sources of range uncertainty are routinely included in treatment range determination for proton therapy. These include uncertainties in CT HU numbers, relative stopping powers of tissues, compensator misalignment, etc. Organ motion is explicitly taken into account in the aperture plane, but not in the beam direction. This study elucidates the magnitude and causes of range variations to well defined points. Inclusion of this uncertainty should be considered in determining treatment range. The project described was supported by Award Number P01CA021239 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.

TH-C-204C-01: A Physicist Perspective of the Use of MRI and Spectroscopy for In-Vivo Verification of Photon and Proton Beam Therapy

The accuracy of radiationdelivery has improved significantly with every technological leap. The improved treatment accuracy has lead to highly conformal dose distributions with subsequent reduction in normal tissue exposure and improved therapeutic ratio. However shrinking PTV margins based on the perceived accuracy of the treatment may lead to geographic misses and subsequent marginal recurrences. For these reasons in‐vivo verification of the delivereddose in patients receiving either X‐ray or proton therapy is of critical importance. Post‐treatment in‐vivo verification may be useful to assess if the treatment has been correctly given. The therapeuticradiation may produce changes within organs that may be used to verify that the target has been adequately treated with the appropriate visualized imaging modality. Magnetic Resonance Imaging(MRI) and spectroscopy (MRS) have the potential of measuring X‐ray and protonradiation induced changes to tumors in the liver brain bone marrow prostate and other sites. In the case of bone marrow studies show marrow changes leading to bright signal intensity within vertebral marrow on T1‐weighted (short T1 inversion recovery STIR) and out‐of‐phase images. The bright marrow signal is thought to represent fatty infiltration after radiation therapy. Histology of radiation effect: two distinct phases of radiation‐induced changes in the bone marrow were observed: 1) acute and 2) chronic. In acute phase radiation caused edema vascular congestion and capillary injury to the fine structure. In addition dilatation of the sinusoids and hemorrhage in the irradiated bone marrow could be detected as early as 1–3 days after irradiation. In the chronic phase hematopoietic cells and blood vessels were depleted and replaced by yellow fat cells. Signal intensity (SI) changes in MR: fatty replacement of irradiated bone marrow was shown to be responsible for SI increase in the Tl‐weighted image due to the shortened T1 relaxation time of the increased fatty content. Hematopoietic elements of the bone marrow are extremely radiosensitive resulting in myeloid depletion if a large volume of marrow is irradiated. Recovery is dose‐dependent and usually occurs with doses bellow 30Gy. Above 50Gy the effects are irreversible. Within days of irradiation there is a transient increase in SI on STIR MRimages due to acute marrow edema necrosis and hemorrhage. After this initial period there is fatty replacement with a consequent increase in signal intensity on T1‐weighted images. In this lecture we will review the physics of MRI and spectroscopy with emphasis on understanding how radiation effects may induce i) local and ii) organ‐wide spin changes visible on an MR. Learning Objectives: 1. Review and discuss MRI and spectroscopy and its benefits to radiationoncology. 2. Present clinical cases where MRI and spectroscopy has been used to visualize and quantify post‐radiation therapy dose distributions. 3. Demonstrate the utility of post‐treatment MRI and spectroscopy