1 Carol Boyd March Case Study March 11, 2013 Intensity modulated radiotherapy (IMRT) for treatment of post-operative high grade glioma in the right parietal region of brain History of Present Illness: Patient NH is a 65 year old male who presented in the emergency room with an onset of seizures in October 2009. A computed tomography (CT) scan showed a 2.5 centimeter (cm) x 3.5 cm mass in the right posterior-parietal lobe with a small hemorrhagic component. The patient was admitted to the hospital for further work up of his brain mass. During his hospital stay, NH underwent a magnetic resonance imaging (MRI) scan that confirmed a 2.5cm x 2.5 cm x 2.5 cm mass in the right posterior-parietal lobe of the brain. A neurosurgeon consulted with the patient and his family about surgical intervention for the brain mass. The patient underwent a craniotomy on November 3, 2009 and the tumor was grossly resected. The surgical pathology report revealed a high grade glioblastoma multiforme (GBM). Upon further discussions at a multidisciplinary tumor board, it was recommended to the patient and his family for NH to undergo radiation therapy and chemotherapy for his diagnosis. In early December 2009, the patient was referred to the radiation oncology department for consultation of post operative radiation therapy to the brain. The radiation oncologist reviewed the patient s medical records and prior imaging studies and recommended partial brain radiation therapy. Potential toxicities, complications and side effects of both early and late reactions were discussed with the patient and his family. The patient agreed to proceed with radiation therapy. Past Medical History: The patient has a past medical history of hypertension. Otherwise, the patient has been a healthy man up until the time of his brain tumor diagnosis. The patient denies any family history of cancer. Social History: The patient worked as a sandblaster and a painter for navy ships. NH has four children. The patient denies any alcohol use and denies any smoking history or illegal drug use. Medications: The patient s list of medications includes Keppra, Hydrochlorothiazide and Temozolomide.
2 Diagnostic Imaging: In late October 2009, NH underwent a CT scan of the brain after an onset of seizures. The CT scan revealed a 2.5 cm round mass demonstrated in the right parietal lobe of the brain. An MRI imaging study performed on November 2, 2009 confirmed a 2.9 cm x 1.8 cm diameter lesion in the right-posterior, parietal region at the gray-white junction. There was no significant displacement of the septum pellucidum from the cranial midline. A craniotomy was performed on November 3, 2009 with a total resection of the gross brain tumor. The pathology of this resection revealed high grade gliobalstoma multiforme. A post-operative MRI performed on November 4, 2009 showed moderate transverse relaxation (T2) hypersensitivity in the margin and hypointensity from hemorrhage within the operative site. There was no contrast enhancement at the margin of the operative site. Radiation Oncologist Recommendations: After review of the patient s medical records and previous imaging studies, the radiation oncologist recommended post-operative, partial brain radiation therapy. The radiation oncologist recommended a plan using a three dimensional conformal radiotherapy (3DCRT) technique to deliver 6000 centigray (cgy) in 30 fractions at 200 cgy per fraction. Using a 3DCRT planning technique will achieve acceptable dose tolerances to normal critical structures and provide adequate target volume coverage. The physician also recommended a plan using an intensity modulated radiation therapy (IMRT) technique for comparison. In general, IMRT improves dose conformity and will allow higher radiation doses to be focused to regions within the tumor while sparing and minimizing dose to normal surrounding critical structures when compared to 3DCRT. 1 The physician requested to use image guided radiation therapy (IGRT) to ensure that the patient is properly aligned on the treatment table as compared to the treatment plan coordinates. The Plan (prescription): The radiation oncologist s treatment recommendation to the medical dosimetrist was to begin a plan using a 3DCRT technique to a dose of 6000 cgy to the planning target volume (PTV). Since the PTV was in close proximity to the brainstem, the radiation oncologist suggested a radiation treatment plan utilizing an IMRT technique to see if the IMRT plan can better spare the dose to the brainstem. Both planning technique will be compared through dose distribution and the dose volume histogram (DVH). Patient Setup / Immobilization: In mid December 2009, NH underwent a CT simulation scan for radiation therapy treatment. Immobilization is very important especially when there are
3 multiple critical structures to avoid during treatment. Effective immobilization can be achieved with the use of a head holding device. 2 The patient was supine on the CT simulation table. The patient s head rested on a Silverman headrest fixed to a Civco S frame head holder. To immobilize the patient for radiation therapy treatment, a thermoplastic face mask with reinforcement strips was customized and molded to the patient s head. Fiducials were then placed on the patient s mask to aid in positioning during treatment (Figure 1). The patient s arms were placed by his side and a knee sponge was placed under the patient s knees for comfort (Figure 2). Once the patient was immobilized, a CT scan was initiated. After the radiation oncologist reviewed and approved the CT simulation scan, the radiation therapist took photos of the patient s position and recorded positioning parameters to document the patient s treatment position. Anatomical Contouring: The CT images were transferred to the Phillip s Pinnacle 8.0m radiation therapy treatment planning system (TPS) in preparation for volume contouring and treatment planning. The medical dosimetrist fused the pre and post-operative MRI imaging studies into the TPS. The radiation oncologist contoured the operative site with the aid of the fused post-operative MRI scan and labeled this volume the clinical target volume (CTV). A 2.5 cm margin was created around the CTV to form the planning target volume (PTV). The medical dosimetrist was instructed to contour the organs at risk (OR) which included the lens of the eyes, the retinae, the brainstem, the optic nerves, the optic chiasm and the brain. After the radiation oncologist reviewed and made adjustments to the OR, a planning goal sheet was given to the medical dosimetrist and treatment planning was initiated. Beam Isocenter / Arrangement: The medical dosimetrist began with a 3DCRT planning technique and placed the isocenter in the middle of the PTV (Figure 3). A 3DCRT plan may increase the target dose coverage, reduce the volume of normal tissue receiving high dose and protect crucial organs from unnecessary exposure. 1 Gantry angles were carefully chosen to avoid going through healthy brain tissue. The medical dosimetrist used the critical organs in a 3D render mode of the TPS to aid in creating beams to avoid entering or exiting through critical structures. The beam arrangement for the 3DCRT plan included gantry angles of 310, 243 and 154 respectively. There was a 0.7-1.0 cm block margin created around the PTV for each beam. A combination of 6 megavoltage (MV) and 18 MV energies were use to optimize the treatment plan. Thirty and 45 wedges were also used to optimize the 3D plan. A comparison trial
4 treatment plan was done using an IMRT planning technique. The isocenter used in the 3DCRT plan was also used in the IMRT plan (Figure 4). Using an IMRT planning technique will allow higher radiation doses to be focused to regions within the tumor while sparing and minimizing dose to surrounding critical structures. Five gantry angles were configured which included beam angles of 160, 88, 16, 304 and 232 respectively. Once the medical dosimetrist configured the gantry angles, the planning objectives, dose constraints and dose prescription were entered into the IMRT parameters portion of the TPS. The field apertures for the IMRT plan were determined automatically by the treatment parameters entered into the TPS. Treatment Planning: The radiation oncologist defined the dose prescription and planning objectives for the 3DCRT and IMRT plan. The tolerance of the normal tissues of the central nervous system (CNS) was carefully observed as it limits the dose of radiation that can be safely delivered. 3 The objective was to configure a 3D plan through the use of multiple non-coplanar fields to the defined target volume and adjust beam weighting, wedge orientation and placement, to minimize cortical dose and maximize dose homogeneity within the high-dose region while providing adequate dose coverage to the target volume. The prescription dose to the 3D plan with 3 non-coplanar fields was prescribed to isocenter placed in the CTV by the medical dosimetrist. Selection of gantry angles was carefully chosen to enter the shortest path through normal brain tissue and avoid entering or exiting through critical structures. The radiation oncologist instructed the medical dosimetrist to place a 1 cm margin block around the PTV for each field. A combination of 6 MV and 18 MV energy beams and wedges were used to optimize the beam weightings. A prescription dose of 6000 cgy at 200 cgy per day for 30 fractions was prescribed to the 3D plan. The patient was planned with IMRT for comparison. The objective of the IMRT plan was to see if dose to critical structures can be further minimized. The PTV was in close proximity to the brainstem. The medical dosimetrist created a planning PTV (PTVbrainstem+ 3 mm) in an attempt to minimize dose to the brainstem. The planning objectives were entered into the IMRT module of the TPS using a uniform, minimum and maximum dose corresponding to the prescription dose. In addition, the OR dose constraints included: a maximum dose to the lens of the eyes less than 300 cgy, the optic nerves less than 500 cgy, the optic chiasm less than 1000 cgy, the retinae less than 800 cgy and the brainstem was to be less than 5000 cgy or as low as possible. An objective was also used to minimize the dose to normal brain tissue. The TPS optimized the IMRT plan by using the direct machine parameter
5 optimization (DMPO). Other optimization parameters included using a maximum number of 50 segments; a minimum segment area of 6 cm 2 and a minimum segment monitor units (MUs) of 6. Once adequate dose coverage was achieved to the target volumes, the medical dosimetrist reviewed the doses to the OR, the isodose lines (Figures 5 and 6) and the dose volume histogram (DVH). The OR on the DVH (Figure 7) reflected a maximum dose of 5931 cgy and 4935 cgy to the 3DCRT and IMRT plan respectively to the brainstem. The maximum dose to the optic chiasm was 1925 cgy and 761 cgy to the 3DCRT plan and IMRT plan respectively. The IMRT plan spared the dose to the lens of the eyes, the optic nerves and the retinas by almost 50 % compared to the 3DCRT. The IMRT plan proved to be more superior in CTV coverage and achieved adequate PTV dose coverage compared to the 3DCRT plan (Figures 8 and 9). In addition, the brainstem and optic chiasm were better spared in the IMRT plan. The radiation oncologist reviewed the plans and chose the IMRT plan for treatment. Quality Assurance/Physics Check: The quality assurance for the IMRT plan was performed using a matrix device for measurement and a gamma function test for analysis. The chambers in the matrix device provide absolute dose measurements along with the dose distribution information that can be compared to the expected doses calculated by the TPS. The gamma function applies the specific criteria to the corresponding pixels from the measured and calculated dose distributions (Figure 10). The QA report was prepared by the medical physicist and was verified and signed by the radiation oncologist. Conclusion: The 3DCRT and the IMRT treatment plans were initiated with care as there were challenges for the medical dosimetrist during treatment planning. One challenge was attempting to avoid having beams enter through critical structures. The medical dosimetrist should turn on all critical structures in 3D mode when designing beams to avoid entering through critical structures if possible. The PTV was adjacent to the brainstem therefore making it difficult to achieve adequate target coverage while minimizing dose to critical structures such as the brainstem. Creating a planning volume to exclude any adjacent structures helped minimize dose to normal critical structures while maximizing target coverage. Although the 3DCRT plan had less beams entering the healthy brain tissue, the IMRT plan yielded better target coverage and proved to be the better plan for minimizing dose to normal critical structures. It is essential for the medical dosimetrist to have a good balance in planning efficiently while controlling toxicity of normal structures to achieve a treatment plan for that will benefit the patient.
6 Figures Figure 1. The patient supine with a customized aquaplast mask. Fiducials are placed on mask to aid in positioning with the use of IGRT during treatment.
7 Figure 2. The patient is supine on the CT simulation table with a knee sponge placed under the knees for comfort.
8 Figure 3. Right anterior oblique (RAO), left posterior oblique (LPO) and right posterior oblique beams for the 3DCRT plan. Figure 4. Left Lateral and anterior-posterior (AP) set up beams for the IMRT plan.
9 Figure 5. CTV coverage of the 3DCRT (dash line) and IMRT (solid line) plan. Figure 6. PTV coverage of 3DCRT (dash line) and IMRT (solid line) plan.
10 Figure 7. DVH of the optic chiasm (blue) and the brainstem (green). Three-dimensional conformal radiotherapy (dash line) IMRT (solid line).
11 Blue isodose line= 6000 cgy Figure 8. The transverse, sagittal and coronal views of the 3DCRT plan.
12 Blue isodose line= 6000 cgy. Figure 9. The transverse, sagittal and coronal views of the IMRT plan.
Figure 10. A Gamma function test analysis for the IMRT treatment plan. 13
14 References 1. Xia P. Optimization of intensity-modulated radiation therapy treatment planning. In: Chao K. Practical Essentials of Intensity Modulated Radiation Therapy. 2 nd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005:20-26. 2. Adams RD, Leaver D. Central nervous system tumors: In: Washington CM, Leaver D, eds. Principals and Practice of Radiation Therapy. 3rd ed. St. Louis Missouri: Mosby, Inc; 2010:745-762. 3. Chan MF, Schupak K, Burman C, Chui CS, Ling CC. Comparison of intensity-modulated radiotherapy with three-dimensional conformal radiation therapy planning for glioblastoma multiforme. Med Dosim. 2003;28(4)261-265. doi:10.1016/j.meddos.2003.08.004.