W.T. Kearns

Neuroanatomical target theory as a predictive model for radiation-induced cognitive decline.

Objective: In a retrospective review to assess neuroanatomical targets of radiation-induced cognitive decline, dose volume histogram (DVH) analyses of specific brain regions of interest (ROI) are correlated to neurocognitive performance in 57 primary brain tumor survivors. Methods: Neurocognitive assessment at baseline included Trail Making Tests A/B, a modified Rey-Osterreith Complex Figure, California or Hopkins Verbal Learning Test, Digit Span, and Controlled Oral Word Association. DVH analysis was performed for multiple neuroanatomical targets considered to be involved in cognition. The %v10 (percent of ROI receiving 10 Gy), %v40, and %v60 were calculated for each ROI. Factor analysis was used to estimate global cognition based on a summary of performance on individual cognitive tests. Stepwise regression was used to determine which dose volume predicted performance on global factors and individual neurocognitive tests for each ROI. Results: Regions that predicted global cognitive outcomes at doses <60 Gy included the corpus callosum, left frontal white matter, right temporal lobe, bilateral hippocampi, subventricular zone, and cerebellum. Regions of adult neurogenesis primarily predicted cognition at %v40 except for the right hippocampus which predicted at %v10. Regions that did not predict global cognitive outcomes at any dose include total brain volume, frontal pole, anterior cingulate, right frontal white matter, and the right precentral gyrus. Conclusions: Modeling of radiation-induced cognitive decline using neuroanatomical target theory appears to be feasible. A prospective trial is necessary to validate these data.

Thoracic re-irradiation using stereotactic body radiotherapy (SBRT) techniques as first or second course of treatment

BACKGROUND AND PURPOSE Management for in-field failures after thoracic radiation is poorly defined. We evaluated SBRT as an initial or second course of treatment re-irradiating in a prior high dose region. MATERIALS AND METHODS Thirty-three patients were treated with re-irradiation defined by the prior 30 Gy isodose line. Kaplan-Meier estimates were performed for local (LC), regional (RC), distant control (DC), and overall survival (OS). The plans when available were summed to evaluate doses to critical structures. Patient and treatment variables were analyzed on UVA for the impact on control and survival measures. RESULTS Median follow-up was 17 months. Treatment for sequential courses was as follows: (course1:course2) EBRT:SBRT (24 patients), SBRT:SBRT (7 patients), and SBRT:EBRT (3 patients). Median re-irradiation dose and fractionation was 50 Gy and 10 fractions (fx), with a median of 18 months (6-61) between treatments. Median OS was 21 months and 2 year LC 67%, yet LC for >1 fraction was 88% (p=0.006 for single vs. multiple). 10 patients suffered chronic grade 2-3 toxicity (6 chest wall pain, 3 dyspnea, 1 esophagitis) and 1 grade 5 toxicity with aorta-esophageal fistula after 54 Gy in 3 fx for a central tumor with an estimated EQD2 to the aorta of 200 Gy. CONCLUSION Tumor control can be established with re-irradiation using SBRT techniques for in-field thoracic failures at the cost of manageable toxicity.

Limited Margins Using Modern Radiotherapy Techniques Does Not Increase Marginal Failure Rate of Glioblastoma.

Objective:We investigate the patterns of failure in the treatment of glioblastoma (GBM) based on clinical target volume (CTV) margin size, dose delivered to the site of initial failure, and the use of temozolomide and intensity-modulated radiotherapy (IMRT). Methods:Between August 2000 and May 2010, 161 patients with GBM were treated with radiotherapy with or without concurrent temozolomide. Patients were treated with CTV expansions that ranged from 5 to 20 mm using a shrinking field technique. Patterns of failure and time to progression and overall survival were compared based on CTV margin, use of temozolomide, and use of IMRT. Kaplan Meier analysis was used to estimate survival times, and &khgr;2 test was used for comparison of cohorts. Results:For patients treated with 5-, 10-, and 15- to 20-mm CTV, 79%, 77%, and 86% experienced failures in the 60 Gy volume, respectively. Forty-eight percent, 55%, and 66% of patients with 5-, 10-, and 15- to 20-mm CTV experienced failures in the 46 Gy volume, respectively. There was no statistical difference between patients treated with 5-, 10-, 15- to 20-mm margins with regard to 60 Gy failure (P=0.76), 46 Gy failure (P=0.51), or marginal failure (P=0.73). Eighty percent of patients receiving temozolomide experienced failures in the 60 Gy volume. There was no increased likelihood of marginal failures in patients receiving IMRT (P=0.97). Conclusions:Modern treatment techniques including use of concurrent temozolmide, limited CTV margin size, and IMRT have not greatly changed the patterns of failure of GBM.

The Observed Variance Between Predicted and Measured Radiation Dose in Breast and Prostate Patients Utilizing an In Vivo Dosimeter

PURPOSE Report the results of using a permanently implantable dosimeter in radiation therapy: determine specific adverse events, degree of migration, and acquire dose measurements during treatment to determine difference between expected and measured dose. METHODS AND MATERIALS The Dose Verification System is a wireless, permanently implantable metal-oxide semiconductor field-effect transistor dosimeter using a bidirectional antenna for power and data transfer. The study cohort includes 36 breast (33 patients received two devices) and 29 prostate (21 patients received two devices) cancer patients. A total of 1,783 and 1,749 daily dose measurements were obtained on breast and prostate patients, respectively. The measurements were compared with the planned expected dose. Biweekly computed tomography scans were obtained to evaluate migration and the National Cancer Institutes Common Toxicity Criteria, version 3, was used to evaluate adverse events. RESULTS Only Grade I/II adverse events of pain and bleeding were noted. There were only four instances of dosimeter migration of >5 mm from known factors. A deviation of > or =7% in cumulative dose was noted in 7 of 36 (19%) for breast cancer patients. In prostate cancer patients, a > or =7% deviation was noted in 6 of 29 (21%) and 8 of 19 (42%) during initial and boost irradiation, respectively. The two patterns of dose deviation were random and systematic. Some causes for these differences could involve organ movement, patient movement, or treatment plan considerations. CONCLUSIONS The Dose Verification System was not associated with significant adverse events or migration. The dosimeter can measure dose in situ on a daily basis. The accuracy and utility of the dose verification system complements current image-guided radiation therapy and intensity-modulated radiation therapy techniques.

Management of Mediastinal Relapse after Treatment with Stereotactic Body Radiotherapy or Accelerated Hypofractionated Radiotherapy for Stage I/II Non–Small-Cell Lung Cancer

Purpose/Objective(s): Regional failures occur in up to 15% of patients treated with stereotactic body radiotherapy (SBRT) for stage I/II lung cancer. This report focuses on the management of the unique scenario of isolated regional failures. Methods: Patients treated initially with SBRT or accelerated hypofractionated radiotherapy were screened for curative intent treatment of isolated mediastinal failures (IMFs). Local control, regional control, progression-free survival, and distant control were estimated from the date of salvage treatment using the Kaplan–Meier method. Results: Among 160 patients treated from 2002 to 2012, 12 suffered IMF and were amenable to salvage treatment. The median interval between treatments was 16 months (2–57 mo). Median salvage dose was 66 Gy (60–70 Gy). With a median follow-up of 10 months, the median overall survival was 15 months (95% confidence interval, 5.8–37 mo). When estimated from original treatment, the median overall survival was 38 months (95% confidence interval, 17–71 mo). No subsequent regional failures occurred. Distant failure was the predominant mode of relapse following salvage for IMF with a 2-year distant control rate of 38%. At the time of this analysis, three patients have died without recurrence while four are alive and no evidence of disease. High-grade toxicity was uncommon. Conclusions: To our knowledge, this is first analysis of salvage mediastinal radiation after SBRT or accelerated hypofractionated radiotherapy in lung cancer. Outcomes appear similar to stage III disease at presentation. Distant failures were common, suggesting a role for concurrent or sequential chemotherapy. A standard full course of external beam radiotherapy is advisable in this unique clinical scenario.

Comparison of accelerated hypofractionation and stereotactic body radiotherapy for Stage 1 and node negative Stage 2 non-small cell lung cancer (NSCLC)

PURPOSE Stereotactic body radiation therapy (SBRT) and accelerated hypofractionated radiation therapy (AHRT) have favorable local control (LC) relative to conventional fractionation in the treatment of stage I non-small cell lung cancer (NSCLC). We report the results of our single institution experience with the treatment of early stage NSCLC with SBRT or AHRT in cases where SBRT was felt to be suboptimal. METHODS One hundred and sixty patients with Stage 1 and node negative Stage 2 NSCLC were treated with SBRT or AHRT from 2003 to 2011. Median follow-up was 29.4 and 19 months (mo), respectively. The median dose was 54Gy in 3 fractions (fx) (SBRT) and 70.2Gy in 26 fx (AHRT). Acute and late toxicities (tox) were graded (G) per CTCAE v4. Time to local (LF), regional (RF) and distant (DF) failure were estimated using the Kaplan-Meier method. The impact of patient and tumor related factors on LF were estimated by multivariate Cox proportional hazard model. RESULTS Three-year LC rates were 87.7% (SBRT) and 71.7% (AHRT). The 3-year freedom from DF was 73.3% and 68.1%. Median OS was 38.4 (95% CI 29.7-51.6) and 35 (95% CI 22-48.3) mo. No G3 or 4 tox were observed. At 1 year, 30% and 50% of complications resolved, while (5-6%) had persistent chest wall pain. Multivariate analysis demonstrated that increasing dose per fraction and tumor size (>5.5 vs. 4cm) in the AHRT and SBRT group were found to be associated with a reduced (HR 0.33 95% CI 0.13-0.84, p=0.021) and increased (HR: 6.372 95% CI 1.23-32.92, p=0.027) hazard for local failure respectively. CONCLUSIONS Our results compare favorably with other reports of treatment for early stage NSCLC. AHRT patients had comparable LC despite increased size and central disease. Toxicity was limited and overall survival, regional and distant recurrences were similar between groups.

Photon spectral characteristics of dissimilar 6 MV linear accelerators

This work measures and compares the energy spectra of four dosimetrically matched 6 MV beams, generated from four physically different linear accelerators. The goal of this work is twofold. First, this study determines whether the spectra of dosimetrically matched beams are measurably different. This study also demonstrates that the spectra of clinical photon beams can be measured as a part of the beam data collection process for input to a three-dimensional (3D) treatment planning system. The spectra of 6 MV beams that are dosimetrically matched for clinical use were studied to determine if the beam spectra are similarly matched. Each of the four accelerators examined had a standing waveguide, but with different physical designs. The four accelerators were two Varian 2100C/Ds (one 6 MV/18 MV waveguide and one 6 MV/10 MV waveguide), one Varian 600 C with a vertically mounted waveguide and no bending magnet, and one Siemens MD 6740 with a 6 MV/10 MV waveguide. All four accelerators had percent depth dose curves for the 6 MV beam that were matched within 1.3%. Beam spectra were determined from narrow beam transmission measurements through successive thicknesses of pure aluminum along the central axis of the accelerator, made with a graphite Farmer ion chamber with a Lucite buildup cap. An iterative nonlinear fit using a Marquardt algorithm was used to find each spectrum. Reconstructed spectra show that all four beams have similar energy distributions with only subtle differences, despite the differences in accelerator design. The measured spectra of different 6 MV beams are similar regardless of accelerator design. The measured spectra show excellent agreement with those found by the auto-modeling algorithm in a commercial 3D treatment planning system that uses a convolution dose calculation algorithm. Thus, beam spectra can be acquired in a clinical setting at the time of commissioning as a part of the routine beam data collection.

Radiation safety issues with positron-emission/computed tomography simulation for stereotactic body radiation therapy.

Stereotactic body radiation therapy (SBRT) simulations using a Stereotactic Body Frame (SBF: Elekta, Stockholm, Sweden) were expanded to include 18F‐deoxyglucosone positron‐emission tomography (FDG PET) for treatment planning. Because of the length of time that staff members are in close proximity to the patient, concerns arose over the radiation safety issues associated with these simulations. The present study examines the radiation exposures of the staff performing SBRT simulations, and provides some guidance on limiting staff exposure during these simulations. Fifteen patients were simulated with PET/CT using the SBF. Patients were immobilized in the SBF before the FDG was administered. The patients were removed from the frame, injected with FDG, and allowed to uptake for approximately 45 minutes. After uptake, the patients were repositioned in the SBF. During the repositioning, exposure rates were recorded at the patients surface, at the SBF surface, and at 15 cm, 30 cm, and 1 m from the SBF. Administered dose and the approximate time spent on patient repositioning were also recorded. The estimated dose to staff was compared with the dose to staff performing conventional diagnostic PET studies. The average length of time spent in close proximity (<50 cm) to the patient after injection was 11.7 minutes, or more than twice the length of time reported for diagnostic PET staff. That time yielded an estimated average dose to the staff of 26.5mSv per simulation. The annual occupational exposure limit is 50 mSv. Based on dose per simulation, staff would have to perform nearly 1900 SBRT simulations annually to exceed the occupational limit. Therefore, at the current rate of 50–100 simulations annually, the addition of PET studies to SBRT simulations is safe for our staff. However, ALARA (“as low as reasonably achievable”) principles still require some radiation safety considerations during SBRT simulations. The PET/CT‐based SBRT simulations are safe and important for treatment planning that optimizes biologic dose distribution with highly accurate and reproducible target definition. PACS numbers: 87.57.uk, 87.59.bd

Radiation safety issues with high activities of liquid I-125: Techniques and experience

The handling of a liquid radioactive source is a procedure that is uncommon for the average clinical medical physicist. A newly approved treatment device utilizes high activities of liquid I‐125 solution as the source of radiation. The radiation safety issues and our experience utilizing high activity liquid I‐125 sources are presented. To date we have treated 22 patients with infused activities ranging up to 26.8 GBq (724 mCi). The careful manipulation of such solutions is important to maintain a safe environment for the patients and the involved medical staff. PACS number(s): 87.53.‐j, 87.52.‐g

Reirradiation for second primary or recurrent cancers of the head and neck: Dosimetric and outcome analysis

The purpose of this study was to examine outcomes, toxicity, and dosimetric characteristics of patients treated with reirradiation for head and neck cancers.