Jean-Pierre Bissonnette

Cone-Beam Computed Tomographic Image Guidance for Lung Cancer Radiation Therapy

PURPOSE To determine the geometric accuracy of lung cancer radiotherapy using daily volumetric, cone-beam CT (CBCT) image guidance and online couch position adjustment. METHODS AND MATERIALS Initial setup accuracy using localization CBCT was analyzed in three lung cancer patient cohorts. The first (n = 19) involved patients with early-stage non-small-cell lung cancer (NSCLC) treated using stereotactic body radiotherapy (SBRT). The second (n = 48) and third groups (n = 20) involved patients with locally advanced NSCLC adjusted with manual and remote-controlled couch adjustment, respectively. For each group, the couch position was adjusted when positional discrepancies exceeded +/-3 mm in any direction, with the remote-controlled couch correcting all three directions simultaneously. Adjustment accuracy was verified with a second CBCT. Population-based setup margins were derived from systematic (Sigma) and random (sigma) positional errors for each group. RESULTS Localization imaging demonstrates that 3D positioning errors exceeding 5 mm occur in 54.5% of all delivered fractions. CBCT reduces these errors; post-correction Sigma and sigma ranged from 1.2 to 1.9 mm for Group 1, with 82% of all fractions within +/-3 mm. For Group 2, Sigma and sigma ranged between 0.8 and 1.8 mm, with 76% of all treatment fractions within +/-3 mm. For Group 3, the remote-controlled couch raised this to 84%, and Sigma and sigma were reduced to 0.4 to 1.7 mm. For each group, the postcorrection setup margins were 4 to 6 mm, 3 to 4 mm, and 2 to 3 mm, respectively. CONCLUSIONS Using IGRT, high geometric accuracy is achievable for NSCLC patients, potentially leading to reduced PTV margins, improved outcomes and empowering adaptive radiation therapy for lung cancer.

A Collaborative Analysis of Stereotactic Lung Radiotherapy Outcomes for Early-Stage Non–Small-Cell Lung Cancer Using Daily Online Cone-Beam Computed Tomography Image-Guided Radiotherapy

Introduction: We report lung stereotactic-body radiotherapy (SBRT) outcomes for a large pooled cohort treated using daily online cone-beam computed tomography. Methods: Five hundred and five stage I–IIB (T1-3N0M0) non–small-cell lung cancer (NSCLC) cases underwent SBRT using cone-beam computed tomography image guidance at five international institutions from 1998 to 2010. Median age was 74 years (range, 42–92) whereas median forced expiratory volume in 1 second/diffusing lung capacity for carbon monoxide were 1.4 liter (65%) and 10.8 ml/min/mmHg (53%). Of the 505 cases, 64% were biopsy proven and 87% medically inoperable. Staging was: IA 63%, IB 33%, IIA 2%, and recurrent 1%. Median max tumor dimension was 2.6 cm (range, 0.9–8.5). Median heterogeneously calculated volumetric prescription dose (PD) was 54 Gy (range, 20–64 Gy) in three fractions (range, 1–15) over 8 days (range, 1–27). Median biologically equivalent PD biological equivalent doses (BED10) was 132 Gy (range, 60–180). Results: With a median follow-up of 1.6 years (range, 0.1–7.3), the 2-year Kaplan–Meier local control (LC), regional control, and distant metastasis (DM) rates were 94%, 89%, and 20%, respectively, whereas cause-specific and overall survival were 87% and 60% (78% operable, 58% inoperable, p = 0.01), respectively. Stage, gross-tumor volume size (≥ 2.7 cm) and PD(BED10) predicted local relapse (LR) and DM. LR was 15% for BED10 less than 105 Gy versus 4% for BED10 of 105 Gy or more (p < 0.001); DM was 31% versus 18% for BED10 less than 105 versus 105 Gy or more (p = 0.01). On multivariate analysis, PD(BED10) and elapsed days during radiotherapy predicted LR; gross-tumor volume size predicted DM. Grade 2 or higher pneumonitis, rib fracture, myositis, and dermatitis were 7%, 3%, 1%, and 2%, respectively. Conclusions: In the largest early-stage NSCLC SBRT data set to date, a high rate of local control was achieved, which was correlated with a PD(BED10) of 105 Gy or more. Failures were primarily distant, severe toxicities were rare, and overall survival was encouraging in operable patients.

Quality assurance for image-guided radiation therapy utilizing CT-based technologies: A report of the AAPM TG-179

PURPOSE Commercial CT-based image-guided radiotherapy (IGRT) systems allow widespread management of geometric variations in patient setup and internal organ motion. This document provides consensus recommendations for quality assurance protocols that ensure patient safety and patient treatment fidelity for such systems. METHODS The AAPM TG-179 reviews clinical implementation and quality assurance aspects for commercially available CT-based IGRT, each with their unique capabilities and underlying physics. The systems described are kilovolt and megavolt cone-beam CT, fan-beam MVCT, and CT-on-rails. A summary of the literature describing current clinical usage is also provided. RESULTS This report proposes a generic quality assurance program for CT-based IGRT systems in an effort to provide a vendor-independent program for clinical users. Published data from long-term, repeated quality control tests form the basis of the proposed test frequencies and tolerances. CONCLUSION A program for quality control of CT-based image-guidance systems has been produced, with focus on geometry, image quality, image dose, system operation, and safety. Agreement and clarification with respect to reports from the AAPM TG-101, TG-104, TG-142, and TG-148 has been addressed.

Quantifying Interfraction and Intrafraction Tumor Motion in Lung Stereotactic Body Radiotherapy Using Respiration-Correlated Cone Beam Computed Tomography

PURPOSE Stereotactic body radiation therapy (SBRT) is an effective treatment for medically inoperable Stage I non-small-cell lung cancer. However, changes in the patients breathing patterns during the course of SBRT may result in a geographic miss or an overexposure of healthy tissues to radiation. However, the precise extent of these changes in breathing pattern is not well known. We evaluated the inter- and intrafractional changes in tumor motion amplitude (DeltaM) over an SBRT course. METHODS AND MATERIALS Eighteen patients received image-guided SBRT delivered in three fractions; this therapy was done with abdominal compression in four patients. For each fraction, cone beam computed tomography (CBCT) was performed for tumor localization (+/- 3-mm tolerance) and then repeated to confirm geometric accuracy. Additional CBCT images were acquired at the midpoint and end of each SBRT fraction. Respiration-correlated CBCT (rcCBCT) reconstructions allowed retrospective assessment of inter- and intrafractional DeltaM by a comparison of tumor displacements in all four-dimensional CT and rcCBCT scans. The DeltaM was measured in mediolateral, superior-inferior, and anterior-posterior directions. RESULTS A total of 201 rcCBCT images were analyzed. The mean time from localization of the tumor to the end-fraction CBCT was 35 +/- 7 min. Compared with the motion recorded on four-dimensional CT, the mean DeltaM was 0.4, 1.0, and 0.4 mm, respectively, in the mediolateral, superior-inferior, and anterior-posterior directions. On treatment, the observed DeltaM was, on average, <1 mm; no DeltaM was statistically different with respect to the initial rcCBCT. However, patients in whom abdominal compression was used showed a statistically significant difference (p < 0.05) in the variance of DeltaM with respect to the initial rcCBCT in the superior-inferior direction. CONCLUSIONS The inter- and intrafractional DeltaM that occur during a course of lung SBRT are small. However, abdominal compression causes larger variations in the time spent on the treatment couch and in the inter- and intrafractional DeltaM values.

Dose–response relationship with clinical outcome for lung stereotactic body radiotherapy (SBRT) delivered via online image guidance☆

PURPOSE To examine potential dose-response relationships with various non-small-cell lung cancer (NSCLC) SBRT fractionation regimens delivered with online CT-based image guidance. METHODS 505 tumors in 483 patients with clinical stage T1-T2N0 NSCLC were treated with SBRT using on-line cone-beam-CT-based image guidance at 5 institutions (1998-2010). Median maximum tumor dimension was 2.6 cm (range 0.9-8.5 cm). Dose fractionation prescription was according to each institutions protocol with the most common schedules of 18-20 GyX3, 12 GyX4, 12 GyX5, 12.5 GyX3, 7.5 GyX8 (median = 54 Gy, 3 fractions). Median prescription (Rx) BED10 = 132 Gy (50.4-180). Median values (Gy) of 3D planned doses for BED10 were GTV(min) = 164.1, GTV(mean) = 188.4, GTV(max) = 205.9, PTV(min) = 113.9, PTV D99 = 123.9, PTV(mean) = 164.7, PTV D1 = 197.3, PTV(max) = 210.7. Mean follow-up = 1.6 years. RESULTS 26 cases (5%) had local recurrence (LR) for a 2-year rate of 6% and 3-year rate of 9%. All BED10 GTV&PTV endpoints were associated with LR as continuous variables on univariate analysis (p<0.05). Rx and PTV(mean) dose appeared to have the highest correlation with LR with area under ROC curve of 0.69 and 0.65 respectively and optimal cut points of 105 and 125 Gy, respectively. 2-year LR was 4% for PTV(mean)>125 vs 17% for <125 Gy (p<0.01) with sensitivity = 84% and specificity = 57% for predicting LR. 2-year LR for Rx BED10>105 was 4% vs 15% for <105 Gy (p<0.01). Longer treatment duration (⩾ 11 elapsed days) demonstrated a 2-year LR of 14% vs 4% for ⩽ 10 days (p<0.01). GTV size was associated with LR on univariate analysis as a continuous variable (p = 0.02) with 2-year LR = 3% for <2.7 cm vs 9% for ⩾ 2.7 cm (p = 0.03). BED10 (p = 0.01) and elapsed days during RT (p = 0.05) were independent predictors on multivariate analysis as continuous variables. CONCLUSIONS There is a substantial dose-response relationship for local control of NSCLC following image-guided SBRT with optimal PTV(mean) BED10>125 Gy. Shorter treatment duration was also associated with better local control in this dataset.

Is there a lower limit of pretreatment pulmonary function for safe and effective stereotactic body radiotherapy for early-stage non-small cell lung cancer?

Introduction: To evaluate the influence of pretreatment pulmonary function (PF) on survival, early and late pulmonary toxicity after stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer. Methods: Four hundred eighty-three patients with 505 tumors of early-stage non-small cell lung cancer cT1–3 cN0 were treated with image-guided SBRT at five international institutions (1998–2010). Sixty-four percent of the tumors were biopsy-proven and 18F-fluorodeoxyglucose-positron emission tomography was performed for staging in 84%. Image-guided SBRT was performed with a median of three fractions to a median total dose of 54 Gy. Pretreatment PF was available for 423 patients, and 617 posttreatment PF tests from 270 patients were available. Results: A large variability of pretreatment PF was observed: the 90% range of forced expiratory volume in 1 second and diffusing capacity for carbon monoxide was 29 to 109% and 5.5 to 19.1 ml/min/mmHg, respectively. PF was significantly correlated with overall survival but not cause-specific survival: diffusing capacity for carbon monoxide of 11.2 ml/min/mmHg differentiated between 3-year overall survival of 66% and 42%. Radiation-induced pneumonitis grade ≥II occurred in 7% of patients and was not increased in patients with lower PF. A significant and progressive change of PF was observed after SBRT: PF decreased by 3.6% and 6.8% on average within 6 and 6 to 24 months after SBRT, respectively. Changes of PF after SBRT were significantly correlated with pretreatment PF: PF improved for worst pretreatment PF and the largest loss was observed for best pretreatment PF. Conclusions: Image-guided SBRT is safe in terms of acute and chronic pulmonary toxicity even for patients with severe pulmonary comorbidities. SBRT should be considered as a curative treatment option for inoperable patients with pretreatment PF as reported in this study.

Trend analysis of radiation therapy incidents over seven years.

PURPOSE To examine incident rates in external beam radiation therapy (RT) as significant changes in technology were introduced. MATERIALS AND METHODS From 2001 to 2007, several technological and practice enhancements were made. All treatment incident reports, including near misses (from 2004), were classified, under a research ethics board approval, according to type (prescription or geometry), cause (location, documentation, non-compliance, laterality, prescribed change, human error, planning/dosimetry, software/hardware malfunction, and accessory), and clinical impact (none, minor, moderate, and severe). Trend analysis was performed retrospectively. RESULTS One thousand and sixty three reports were analyzed. The average incident rate per 100 RT course was 1.7+/-0.4; excluding near misses, this rate fell to 1.4+/-0.3. Both rates showed a downward trend. The occurrence of events due to treatment accessories (0.75-0.28), prescribed changes to treatment parameters (0.17-0.03), and location (0.41-0.17) have decreased, while documentation-related incidents have risen (0.03-0.37). The proportion of incidents is highest at the planning and treatment stages. CONCLUSION Our analysis has shown that while technological and process enhancements can reduce certain error pathways, others can be created. Trends in incident rates have been assessed, indicating robustness of our practice in view of these changes.

Quality assurance for the geometric accuracy of cone-beam CT guidance in radiation therapy.

The introduction of volumetric X-ray image-guided radiotherapy systems allows improved management of geometric variations in patient setup and internal organ motion. As these systems become a routine clinical modality, we propose a daily quality assurance (QA) program for cone-beam computed tomography (CBCT) integrated with a linear accelerator. The image-guided system used in this work combines a linear accelerator with conventional X-ray tube and an amorphous silicon flat-panel detector mounted orthogonally from the accelerator central beam axis. This article focuses on daily QA protocols germane to geometric accuracy of the CBCT systems and proposes tolerance levels on the basis of more than 3 years of experience with seven CBCT systems used in our clinic. Monthly geometric calibration tests demonstrate the long-term stability of the flex movements, which are reproducible within +/-0.5 mm (95% confidence interval). The daily QA procedure demonstrates that, for rigid phantoms, the accuracy of the image-guided process can be within 1 mm on average, with a 99% confidence interval of +/-2 mm.

A quality assurance program for image quality of cone-beam CT guidance in radiation therapy

The clinical introduction of volumetric x-ray image-guided radiotherapy systems necessitates formal commissioning of the hardware and image-guided processes to be used and drafts quality assurance (QA) for both hardware and processes. Satisfying both requirements provides confidence on the systems ability to manage geometric variations in patient setup and internal organ motion. As these systems become a routine clinical modality, the authors present data from their QA program tracking the image quality performance of ten volumetric systems over a period of 3 years. These data are subsequently used to establish evidence-based tolerances for a QA program. The volumetric imaging systems used in this work combines a linear accelerator with conventional x-ray tube and an amorphous silicon flat-panel detector mounted orthogonally from the accelerator central beam axis, in a cone-beam computed tomography (CBCT) configuration. In the spirit of the AAPM Report No. 74, the present work presents the image quality portion of their QA program; the aspects of the QA protocol addressing imaging geometry have been presented elsewhere. Specifically, the authors are presenting data demonstrating the high linearity of CT numbers, the uniformity of axial reconstructions, and the high contrast spatial resolution of ten CBCT systems (1-2 mm) from two commercial vendors. They are also presenting data accumulated over the period of several months demonstrating the long-term stability of the flat-panel detector and of the distances measured on reconstructed volumetric images. Their tests demonstrate that each specific CBCT system has unique performance. In addition, scattered x rays are shown to influence the imaging performance in terms of spatial resolution, axial reconstruction uniformity, and the linearity of CT numbers.

Image guided radiation therapy (IGRT) technologies for radiation therapy localization and delivery.

Image Guided Radiation Therapy (IGRT) Technologies for Radiation Therapy Localization and Delivery Jennifer De Los Santos, MD,* Richard Popple, PhD,* Nzhde Agazaryan, PhD,y John E. Bayouth, PhD,z Jean-Pierre Bissonnette, PhD,x Mary Kara Bucci, MD,k Sonja Dieterich, PhD,{ Lei Dong, PhD, Kenneth M. Forster, PhD,** Daniel Indelicato, MD,yy Katja Langen, PhD,zz Joerg Lehmann, PhD,{ Nina Mayr, MD,xx Ishmael Parsai, PhD,{{ William Salter, PhD, Michael Tomblyn, MD, MS,*** William T.C. Yuh, MD, MSEE,kk and Indrin J. Chetty, PhDyyy *Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, Alabama; yDepartment of Radiation Oncology, University of California Los Angeles, Los Angeles, California; zDepartment of Radiation Oncology, University of Iowa, Iowa City, Iowa; xDepartment of Radiation Physics, Princess Margaret Hospital, Toronto, Ontario, Canada; kAnchorage Radiation Therapy Center, Anchorage, Alaska; {Department of Radiation Oncology, University of California Davis, Sacramento, California; Scripps Proton Therapy Center, San Diego, California; **Department of Radiation Oncology, University of South Alabama, Mobile, Alabama; yyDepartment of Radiation Oncology, University of Florida Proton Therapy Institute, Jacksonville, Florida; zzDepartment of Radiation Oncology, MD Anderson Cancer Center Orlando, Orlando, Florida; Departments of xxRadiation Oncology and kkRadiology, Ohio State University, Columbus, Ohio; {{Department of Radiation Oncology, University of Toledo College of Medicine, Toledo, Ohio; Department of Radiation Oncology, Huntsman Cancer Hospital, Salt Lake City, Utah; ***Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida; and yyyDepartment of Radiation Oncology, Henry Ford Hospital and Health Centers, Detroit, Michigan