Quality assurance for nonradiographic radiotherapy localization and positioning systems: report of Task Group 147.

New technologies continue to be developed to improve the practice of radiation therapy. As several of these technologies have been implemented clinically, the Therapy Committee and the Quality Assurance and Outcomes Improvement Subcommittee of the American Association of Physicists in Medicine commissioned Task Group 147 to review the current nonradiographic technologies used for localization and tracking in radiotherapy. The specific charge of this task group was to make recommendations about the use of nonradiographic methods of localization, specifically; radiofrequency, infrared, laser, and video based patient localization and monitoring systems. The charge of this task group was to review the current use of these technologies and to write quality assurance guidelines for the use of these technologies in the clinical setting. Recommendations include testing of equipment for initial installation as well as ongoing quality assurance. As the equipment included in this task group continues to evolve, both in the type and sophistication of technology and in level of integration with treatment devices, some of the details of how one would conduct such testing will also continue to evolve. This task group, therefore, is focused on providing recommendations on the use of this equipment rather than on the equipment itself, and should be adaptable to each user's situation in helping develop a comprehensive quality assurance program.

Prostate intrafraction translation margins for real-time monitoring and correction strategies.

The purpose of this work is to determine appropriate radiation therapy beam margins to account for intrafraction prostate translations for use with real-time electromagnetic position monitoring and correction strategies. Motion was measured continuously in 35 patients over 1157 fractions at 5 institutions. This data was studied using van Herk's formula of (αΣ + γσ') for situations ranging from no electromagnetic guidance to automated real-time corrections. Without electromagnetic guidance, margins of over 10 mm are necessary to ensure 95% dosimetric coverage while automated electromagnetic guidance allows the margins necessary for intrafraction translations to be reduced to submillimeter levels. Factors such as prostate deformation and rotation, which are not included in this analysis, will become the dominant concerns as margins are reduced. Continuous electromagnetic monitoring and automated correction have the potential to reduce prostate margins to 2-3 mm, while ensuring that a higher percentage of patients (99% versus 90%) receive a greater percentage (99% versus 95%) of the prescription dose.

Off-label use of medical products in radiation therapy: summary of the report of AAPM Task Group No. 121.

Medical products (devices, drugs, or biologics) contain information in their labeling regarding the manner in which the manufacturer has determined that the products can be used in a safe and effective manner. The Food and Drug Administration (FDA) approves medical products for use for these specific indications which are part of the medical product's labeling. When medical products are used in a manner not specified in the labeling, it is commonly referred to as off-label use. The practice of medicine allows for this off-label use to treat individual patients, but the ethical and legal implications for such unapproved use can be confusing. Although the responsibility and, ultimately, the liability for off-label use often rests with the prescribing physician, medical physicists and others are also responsible for the safe and proper use of the medical products. When these products are used for purposes other than which they were approved, it is important for medical physicists to understand their responsibilities. In the United States, medical products can only be marketed if officially cleared, approved, or licensed by the FDA; they can be used if they are not subject to or specifically exempt from FDA regulations, or if they are being used in research with the appropriate regulatory safeguards. Medical devices are either cleared or approved by FDA's Center for Devices and Radiological Health. Drugs are approved by FDA's Center for Drug Evaluation and Research, and biological products such as vaccines or blood are licensed under a biologics license agreement by FDA's Center for Biologics Evaluation and Research. For the purpose of this report, the process by which the FDA eventually clears, approves, or licenses such products for marketing in the United States will be referred to as approval. This report summarizes the various ways medical products, primarily medical devices, can legally be brought to market in the United States, and includes a discussion of the approval process, along with manufacturers' responsibilities, labeling, marketing and promotion, and off-label use. This is an educational and descriptive report and does not contain prescriptive recommendations. This report addresses the role of the medical physicist in clinical situations involving off-label use. Case studies in radiation therapy are presented. Any mention of commercial products is for identification only; it does not imply recommendations or endorsements of any of the authors or the AAPM. The full report, containing extensive background on off-label use with several appendices, is available on the AAPM website (http://www.aapm.org/pubs/reports/).

Efficient use of continuous, real-time prostate localization.

Recent technological advances make it possible to monitor prostate movement during radiation delivery. Using previously published data from 35 patients who underwent continuous localization during prostate cancer treatment, we simulated various interventions to identify the radiation-gating and patient-repositioning strategies that least prolonged the time to complete the daily treatment. Acceptable response protocols were those that resulted in at least 95% of patients' prostates remaining within the planning margins at least 95% of the time. Gating and repositioning were not necessary for margins of 7 or 10 mm because of the rarity of excursions at these margins. However, intervention was routinely necessary for margins of 3 and 5 mm. In simulated interventions for which the therapist could reposition the treatment couch without entering the room, the most time-efficient response protocol was to reposition the couch immediately after the prostate position was outside the treatment margins. In simulations in which the therapist had to enter the room to reposition the couch, overall treatment time could be reduced and accuracy could be increased by manually gating treatment for 11 and 21 s for 3- and 5-mm margins, respectively, before interrupting treatment to reposition the treatment couch.

Multi-institutional clinical experience with the Calypso System in localization and continuous, real-time monitoring of the prostate gland during external radiotherapy.

PURPOSE: To report the clinical experience with an electromagnetic treatment target positioning and continuous monitoring system in patients with localized prostate cancer receiving external beam radiotherapy. METHODS AND MATERIALS: The Calypso System is a target positioning device that continuously monitors the location of three implanted electromagnetic transponders at a rate of 10 Hz. The system was used at five centers to position 41 patients over a full course of therapy. Electromagnetic positioning was compared to setup using skin marks and to stereoscopic X-ray localization of the transponders. Continuous monitoring was performed in 35 patients. RESULTS: The difference between skin mark vs. the Calypso System alignment was found to be >5 mm in vector length in more than 75% of fractions. Comparisons between the Calypso System and X-ray localization showed good agreement. Qualitatively, the continuous motion was unpredictable and varied from persistent drift to transient rapid movements. Displacements > or =3 and > or =5 mm for cumulative durations of at least 30 s were observed during 41% and 15% of sessions. In individual patients, the number of fractions with displacements > or =3 mm ranged from 3% to 87%; whereas the number of fractions with displacements > or =5 mm ranged from 0% to 56%. CONCLUSION: The Calypso System is a clinically efficient and objective localization method for positioning prostate patients undergoing radiotherapy. Initial treatment setup can be performed rapidly, accurately, and objectively before radiation delivery. The extent and frequency of prostate motion during radiotherapy delivery can be easily monitored and used for motion management.

A multicenter, randomized, dose-finding study of gamma intracoronary radiation therapy to inhibit recurrent restenosis after stenting.

OBJECTIVES: The objective of this double-blind, randomized study was to determine the safety and efficacy of intracoronary radiation therapy (ICRT) with a dose of 17 Gray (Gy) compared to the currently recommended dose prescription of 14 Gy for the treatment of in-stent restenosis within bare metal stents. BACKGROUND: While gamma ICRT for in-stent restenosis has been proven efficacious, the optimal dose is unknown, and radiation failure due to recurrent neointimal hyperplasia remains a significant clinical problem for some patients. A higher radiation dose may improve outcomes, but may potentially increase adverse events. METHODS: Following coronary intervention, 336 patients with in-stent restenosis were randomly assigned to receive ICRT with either 14 Gy or 17 Gy at 2 mm from an 192-iridium source. RESULTS: At 8-month follow up, fewer patients in the 17 Gy group underwent target lesion revascularization (TLR = 15.2% versus 27.2%; p = 0.01), target vessel revascularization (21.3% versus 33.1%; p = 0.02), or reached the composite endpoint of death, myocardial infarction, thrombosis, or TLR (17.1% versus 28.4%; p = 0.02). There were no differences in late thrombosis or mortality between treatment groups. There was a strong trend toward reduced in-lesion late loss (0.36 +/- 0.63 mm vs. 0.51 +/- 0.64 mm; p = 0.09) and a significantly lower rate of binary restenosis (23.9% versus 38.1%; p = 0.031) in the high dose group. CONCLUSIONS: Gamma ICRT with 17 Gy is safe and, compared to 14 Gy, reduces recurrent stenosis and clinical events at 8-month follow up. An increase in the currently recommended gamma radiation dose prescription from 14 Gy to 17 Gy should be strongly considered.

Long-term outcome of patients treated with repeat percutaneous coronary intervention after failure of gamma-brachytherapy for the treatment of in-stent restenosis.

BACKGROUND: Although (192)Ir intracoronary brachytherapy has been demonstrated to dramatically reduce the recurrence of in-stent restenosis, up to 24% of these patients will still require repeat target-vessel revascularization. The short- and long-term outcomes of repeat percutaneous intervention in this population have not been characterized. METHODS AND RESULTS: Analysis was performed of all patients enrolled in the GAMMA-I and GAMMA-II brachytherapy trials who underwent repeat percutaneous target lesion revascularization (TLR) because of restenosis. Subjects were divided into 2 cohorts: those who had received (192)Ir brachytherapy and those randomized to placebo. Forty-five (17.6%) of a total of 256 patients whose index treatment was intracoronary radiation therapy and 36 (29.8%) of 121 patients whose index treatment was placebo required repeat percutaneous TLR. The mean time to this first TLR was 295+/-206 days in the irradiated group and 202+/-167 days in the placebo group (P=0.03). Acute procedural success occurred in 100% of irradiated patients and 94% of placebo controls (P=0.19). After the first TLR, a subsequent TLR was required in 15 (33.3%) of 45 brachytherapy patients versus 17 (47.2%) of 36 placebo failure patients (P=0.26). There was no significant difference in time to second TLR between the 2 groups. Other long-term major adverse event rates in both groups were comparable to those of other contemporary angioplasty/stenting series. CONCLUSIONS: In those patients who "fail" (192)Ir intracoronary brachytherapy for in-stent restenosis, treatment with (192)Ir delays the time to first TLR. Additionally, repeat percutaneous intervention in these patients is safe and efficacious in the short term, with acceptable long-term results.

Five-year clinical follow-up after intracoronary radiation: results of a randomized clinical trial.

BACKGROUND: Several clinical trials indicate that intracoronary radiation is safe and effective for treatment of restenotic coronary arteries. We previously reported 6-month and 3-year clinical and angiographic follow-up demonstrating significant decreases in target lesion revascularization (TLR) and angiographic restenosis after gamma radiation of restenotic lesions. The objective of this study was to document the clinical outcome 5 years after treatment of restenotic coronary arteries with catheter-based iridium-192 (192Ir). METHODS AND RESULTS: A double-blind, randomized trail compared 192Ir to placebo sources in patients with restenosis after coronary angioplasty. Over a 9-month period, 55 patients were enrolled; 26 were randomized to 192Ir and 29 to placebo. At 5-year follow-up, TLR was significantly lower in the 192Ir group (23.1% versus 48.3%; P=0.05). There were 2 TLRs between years 3 and 5 in patients in the 192Ir group and none in patients in the placebo group. The 5-year event-free survival rate (freedom from death, myocardial infarction, or TLR) was greater in 192Ir-treated patients (61.5% versus 34.5%; P=0.02). CONCLUSIONS: Despite apparent mitigation of efficacy over time, there remains a significant reduction in TLR at 5 years and an improvement in event-free survival in patients treated with intracoronary 192Ir. The early clinical benefits after intracoronary gamma radiation with 192Ir seem durable at 5-year clinical follow-up.

Centered versus noncentered source for intracoronary artery radiation therapy: a model based on the Scripps Trial.

BACKGROUND: The Scripps Trial was a randomized study of intracoronary artery radiation therapy with iridium 192 used to treat restenotic vessels. We used the intravascular ultrasound data from the Scripps Trial to investigate whether a lumen-centered gamma or beta radiation source would reduce radiation dose heterogeneity compared with the noncentered source position used. METHODS: Analysis included 28 patients with stent placement in 20 native vessels and 8 saphenous vein grafts enrolled in this trial. Radiation dosimetry for gamma radiation was calculated to deliver 800 cGy to the far field target, provided the maximum dose to the near field target did not exceed 3000 cGy. Prescribed dosimetry for beta radiation by use of yttrium 90 was 1600 cGy at 2 mm distance from the source. RESULTS: The calculated average minimum source to target distance by use of a lumen-centered source increased by 0.18 mm from 1.70 +/- 0.25 to 1.88 +/- 0.36 mm, whereas the maximum distance decreased by 0.17 mm from 3.64 +/- 0.60 to 3.47 +/- 0.43 mm (P <.05). On the basis of these distances, the maximum radiation dose, as well as radiation dose heterogeneity (ratio of maximum to minimum), would have been reduced in 22 of 28 patients by use of a lumen-centered gamma or beta source (P <.005). The reduction in dose heterogeneity was substantially greater with a beta source compared with a gamma source (48% vs 16% reduction). CONCLUSIONS: Centering of the intracoronary artery radiation therapy delivery catheter within the vessel lumen can significantly reduce radiation dose heterogeneity when compared with a noncentered source position. This dose reduction is substantially greater for a beta compared with a gamma source.