John H. Heinzerling

FOUR-DIMENSIONAL COMPUTED TOMOGRAPHY SCAN ANALYSIS OF TUMOR AND ORGAN MOTION AT VARYING LEVELS OF ABDOMINAL COMPRESSION DURING STEREOTACTIC TREATMENT OF LUNG AND LIVER

PURPOSE To investigate the effectiveness of different abdominal compression levels on tumor and organ motion during stereotactic body radiotherapy of lower lobe lung and liver tumors using four-dimensional (4D)-CT scan analysis. METHODS AND MATERIALS Three 4D-CT scans were acquired for 10 patients first using with no compression and then compared with two different levels of abdominal compression. The position of the tumor and various organs were defined at the peak inspiratory and expiratory phases and compared to determine the maximum motion. RESULTS Mean (+/-SD) medium compression force (MC) and high compression force (HC) were 47.6 +/- 16.0 N and 90.7 +/- 27.1 N, respectively. Mean overall tumor motion was 13.6 mm (2sigma [2 sigma] 11.5-15.6), 8.3 mm (2sigma 6.0-10.5), and 7.2 mm (2sigma 5.4-9.0) for no compression, MC, and HC, respectively. A significant difference in the control of both superior-inferior (SI) and overall motion of tumors was seen with the application of MC and HC when compared with no compression (p < 0.0001 for both). High compression force improved SI and overall tumor motion compared with MC, but this was only significant for SI motion (p = 0.04 and p = 0.06). Significant control of organ motion was only seen in the pancreas (p = 0.01). CONCLUSIONS Four-dimensional CT shows significant control of both lower lobe lung and liver tumors using abdominal compression. High levels of compression improve SI tumor motion when compared with MC.

Stereotactic ablative radiation therapy for primary lung tumors.

Stereotactic ablative radiotherapy, also known as stereotactic body radiation therapy, has been developed as an innovative therapy for stage I non-small cell lung cancer and has now emerged as a standard treatment option for medically inoperable patients through careful analysis utilizing prospective, multi-institutional trials. This article reviews and updates the evidence for use of stereotactic ablative radiotherapy in medically inoperable patients with stage I lung cancer, its extension of use to medically operable patients, and the toxicities associated with this emerging technique.

Stereotactic Body Radiation Therapy for Thoracic Cancers: Recommendations for Patient Selection, Setup and Therapy

Advanced technologies have facilitated the development of stereotactic body radiation therapy (SBRT) programs capable of delivering ablative radiation doses for the control of lung cancers. To date, experience with these programs has been highly favorable, as reflected in the results of careful clinical trials. The medically inoperable lung cancer patient, lacking more effective options, has served as the initial clinical base to test SBRT; the therapeutic outcomes have confirmed a significant role for this approach. For many patient groups, SBRT may become a noninvasive alternative to some thoracic surgeries, especially ones with more limited therapeutic goals such as wedge resection. Despite these results, long-term evaluation of the cases treated is required to allow greater understanding of the limitations and contributions of this new modality. The successful delivery of SBRT requires the development of a comprehensive, specialized clinical program providing advanced technology and the technical expertise of physicians, physicists and therapists specially trained in SBRT applications. To achieve successful clinical outcomes, careful patient selection and attention to therapy design and delivery are required since exacting clinical procedures are involved. This chapter will outline many details essential for establishing an effective SBRT program in clinical practice.

Optimization of normalized prescription isodose selection for stereotactic body radiation therapy: Conventional vs robotic linac

PURPOSE Although modern technology has allowed for target dose escalation by minimizing normal tissue dose, the dose delivered to a tumor and surrounding tissues still depends largely on the inherent characteristics of the radiation delivery platform. This work aims to determine the optimal prescription isodose line that minimizes normal tissue irradiation for stereotactic body radiation therapy (SBRT) for a conventional linear accelerator and a robotic delivery platform. METHODS Spherical targets with diameters of 10, 20, and 30 mm were constructed in the lungs and liver of a computer based digital torso phantom which simulates respiratory and cardiac motion. Normal tissue contours included normal lung, normal liver, and a concentric 10 mm shell of normal tissue extending from the spherical target surface. For linac planning, noncoplanar, nonopposing three dimensional (3D) conformal beams were designed, and variable prescription isodose lines were achieved by varying the MLC block margin. For CyberKnife planning, variable prescription isodose lines were achieved by inverse planning. True 4D dose calculations were used for the moving target and surrounding tissue based on each of ten phases of a 4D CT dataset. Doses of 60 Gy in three fractions were prescribed to cover 95% of the target tumor. Commonly used conformality, dosimetric, and radiobiological indices for lung and liver SBRT were used to compare different plans and determine the optimally prescribed isodose line for each treatment platform. RESULTS For linac plans, the average optimal prescription isodose line based on all indices evaluated occurred between 59% and 69% for lung tumors and between 67% and 77% for liver tumors depending on the tumor size. CyberKnife plans had average optimal prescription isodose lines occurring between 40% and 48% for lung tumors and between 41% and 42% depending on the tumor size. However, prescription isodose lines under 50% are not advised to prevent large heterogeneous dose distributions within the target. CONCLUSIONS The choice of prescription isodose line was shown to have a significant impact on parameters commonly used as constraints for lung and liver SBRT treatment planning for both linac-based and CyberKnife delivery platforms. By methodically choosing the prescription isodose line, normal tissue toxicities from SBRT may be reduced.

Toxicity and Response of Pemetrexed Plus Carboplatin or Cisplatin with Concurrent Chest Radiation Therapy for Patients with Locally Advanced Non-small Cell Lung Cancer: A Phase I Trial

Introduction: Pemetrexed is an effective and a tolerable drug in advanced non-small cell lung cancer (NSCLC). This study sought to ascertain maximum tolerated dose (MTD) and phase II dose of carboplatin or cisplatin given with pemetrexed and concurrent chest radiation therapy (CRT) in locally advanced NSCLC. Methods: Eligible, previously untreated patients were enrolled with the initial intent of establishing the MTD of both weekly cisplatin or carboplatin combined with pemetrexed 500 mg/m2 every 3 weeks and concurrent CRT in an alternating, two arm, phase I trial. Secondary objectives included response rate and toxicity. The protocol was subsequently amended to establish the safety of planned phase II doses of cisplatin or carboplatin combined with pemetrexed 500 mg/m2 given every 3 weeks × 3 cycles with CRT. Results: Patients received pemetrexed combined with carboplatin area under curve = 2 (n = 9), cisplatin 30 mg/m2 (n = 9), or cisplatin 75 mg/m2 (n = 4). One dose-limiting toxicity occurred in both the carboplatin and in the cisplatin 30 mg/m2 cohorts. No dose-limiting toxicities occurred in the cisplatin 75 mg/m2 cohort. Because these are standard doses without radiation therapy in lung cancer, there was no further dose escalation. Partial response rates were 11% (carboplatin) and 46% (combined cisplatin). Stable disease rates were 33% (carboplatin) and 46% (combined cisplatin). Two patients receiving carboplatin experienced disease progression. Conclusions: The MTD of cisplatin combined with pemetrexed was not reached. Based on these and Cancer and Leukemia Group B 30407 results, pemetrexed with either carboplatin or cisplatin at full systemic doses with CRT seems to be well tolerated. A multicenter, randomized phase II trial of both regimens is underway.

Stereotactic body radiation therapy: evaluation of setup accuracy and targeting methods for a new couch integrated immobilization system.

A new stereotactic frame system was designed at Indiana University to utilize the precision motion control of newer accelerator couches and treat obese patients previously untreatable in other frame systems during stereotactic body radiation therapy (SBRT). The repositioning accuracy and target reproducibility of this frame was evaluated in the treatment of both lung and liver tumors. The external coordinate system on the new frame was validated using a phantom system. Translational motions were carried out using couch motors. Five patients were treated with SBRT and twenty-three verification CT scans were acquired. The displacement of the gross tumor volume (GTV) and adjacent vertebral body between the original CT scan and the verification CT scans was determined. The mean setup accuracy for the patient study was less than 5 mm. Mean displacement of the GTV was 3.0 mm (0.0–6.0 mm) in the lateral (x) direction, 4.1 mm (0.0–8.9 mm) in the superior-inferior (y) direction, and 2.6 mm (0.0–10.0 mm) in the cranio-caudal (z) direction. Comparison of vertebral body position showed mean displacement of 2.4 mm (0.0 to 8.0 mm), 1.9 mm (0.0 mm to 2.0 mm), and 0.9 mm (0.0 to 5.0 mm) for the same shift directions. Repositioning could be accurately carried out from an initial reference position using the treatment couch controllers. Adequate set-up accuracy using a frame system capable of accommodating wide girth patients was achieved and was comparable to other published studies for narrower frames. With these results, a 5 mm expansion for PTV margins remains the standard for our institution.

Stereotactic Ablative Radiotherapy for Early Stage Lung Cancer

Stereotactic ablative radiotherapy (SABR), also known as stereotactic body radiation therapy (SBRT) utilizes advanced techniques of immobilization, image guidance, and unique field arrangements to deliver precise, oligofractionated radiotherapy to a variety of tumor types. SABR has been established as a technologically innovative therapy for early stage non-small cell lung cancer (NSCLC) and has emerged as the standard treatment option for medically inoperable patients through utilization of prospective, multi-institutional trials. Recent trials continue to evaluate the role of SABR in the medically operable and borderline operable population, and will compare surgical resection and SABR as treatment modalities in these patients. This chapter reviews the techniques utilized in SABR, the evidence for use of SABR in early stage lung cancer, its extension of use to medically operable patients, and the toxicities associated with this emerging technique.

SU‐E‐T‐539: Dosimetric Evaluation of PTV Margins and Intrafraction Motion for Prostate SBRT

Purpose: We have initiated a phase I/II prostate SBRT trial using doses up to 50 Gy delivered in 5 fractions. With the small requisite margins, intrafraction prostate motion may compromise target coverage and/or dose to organs at risk. The purpose of this study is to investigate CTV coverage and dose to normal tissues, in the presence of intrafraction prostate motion, when different PTV margins and rectal immobilization strategies are employed. Methods: Nine prostate cancer patients treated with a rectal balloon and stereotactic body frame were selected for this study. Patients received 50 Gy in five fractions delivered with 13 coplanar 10 MV photon beams. The SBRT plans used 0, 1,2, and 3mm PTV margins. The tracking data from the Calypso Localization System were used to calculate motion probability density functions(PDFs). Calypso tracking data from conventionally fractionated prostate patients, treated without rectal balloons, were used to generate another set of PDFs. The planned static dose distributions were convolved with the PDFs to generate the delivered dose distributions. The planned and delivered doses were evaluated. Results: The mean planned dose to the CTV, PTV and bladder was slightly higher than the delivered dose. The CTV volume covered by the prescription dose decreased when intrafraction motion is accounted for, but remains 100% with 3mm margins and greater than 97% for no PTV margin. The mean planned dose to anterior rectal wall was less than the delivered dose and the conventionally fractionated group was higher than the SBRT group. Conclusions: This study demonstrates that the dosimetric impact of intrafraction motion during prostate SBRT delivery with 3mm margins is not clinically significant with or without a rectal balloon. Use of a rectal balloon can reduce the delivered dose to the rectum and the severity of early bowel toxicity.