Blue Cross Blue Shield of Montana (BCBSMT) considers real-time intra-fraction target tracking during radiation therapy to adjust radiation doses or monitor target movement during individual radiation therapy treatment sessions not medically necessary.
When the criteria for coverage is not met, BCBSMT encourages all participating providers to have a member complete and sign an Advanced Member Notification (AMN) form stating that BCBSMT will not cover this service, supply, device, or drug. If an AMN is signed prior to delivery of the service, participating providers can balance bill the patient. If an AMN is not signed, participating providers are financially liable and cannot balance bill the BCBSMT member for denied services. Services provided by an out-of-state provider that are denied as not medically necessary are the financial responsibility of the patient even if an AMN is signed.
Refer to the Advanced Member Notification medical policy for more information. The AMN form is available at https://www.bcbsmt.com (Click on Providers and then Forms).
Randomized trial data are needed to show the impact on clinical outcomes of real-time tracking devices that allow for adjustments during radiation therapy or monitor the tumor target during individual treatment sessions. The clinical outcomes could be disease control (patient survival) and/or toxicity (e.g., less damage to adjacent normal tissue). Since intensity-modulated radiation therapy (IMRT) and IMRT plus real-time tracking are likely to produce equivalent therapeutic results, given the increased cost of real-time tracking, the technique (tracking) needs to demonstrate incremental clinical benefit over IMRT. To date, clinical outcome studies have not been reported for any tumor site but will be required to show that target tracking during radiotherapy leads to a clinically meaningful change in outcomes. The majority of the work in this evolving area is in prostate cancer, although there are also studies of the technique in other organs such as lung and breast.
Studies have focused on movement of the target during radiation therapy sessions. This is considered an initial step in evaluating this technology, but is not sufficient to determine if patient outcomes are improved. As Dawson and Jaffray comment, the clinically meaningful thresholds for target tracking and re-planning of treatment during a course of radiation therapy are not yet known. (2) Even less is known about the impact of target tracking within a single treatment session.
These new devices do appear to provide accurate localization. Santanam and colleagues reported on the localization accuracy of electromagnetic tracking systems and on-board imaging systems. (3) In this study, both the imaging system and the electromagnetic system showed submillimeter accuracy during a study of both a phantom and a canine model. Kindblom et al. similarly showed electromagnetic tracking was feasible with the Micropos transponder system and that the accuracy of transponder localization was comparable to x-ray localization of radiopaque markers. (4) Smith et al. successfully coupled an electromagnetic tracking system with linear accelerator gating for lung cancer. (5) A currently registered trial is looking at the movement of the cervix during radiation therapy.
In the 2009, National Comprehensive Cancer Network (NCCN) clinical practice guidelines for prostate cancer, state “The accuracy of treatment should be improved by attention to daily prostate localization, with techniques such as IGRT using CT, ultrasound implanted fiducials, electromagnetic targeting/tracking, or an endorectal balloon to improve oncologic cure rates and reduce side effects.” (6) NCCN has also added IGRT to all 3D-CRT/IMRT treatment regimens. NCCN is applying a broader definition of IGRT and is addressing inter-fraction (daily) adjustment rather than intra-fraction adjustments, which are the focus of this policy. Although NCCN states that unless otherwise noted, all recommendations are based on level 2A evidence, no specific citations are provided for basis of their conclusions.
In a retrospective analysis of data collected from the treatment of 21 patients with prostate cancer treated with Cyberknife, Xie et al. reported on the intra-fractional movement of the prostate during hypofractionated radiotherapy. (7) The analysis included 427 datasets composed of the time it took for the prostate to move beyond an acceptable level (approximately 5 mm). The data suggest that it takes approximately 697 seconds for the prostate to move beyond 5 mm relative to its planned position and that motion of greater than 2 mm at 30 seconds was present in approximately 5% of datasets. The percentage increases to 8%, 11%, and 14% at 60, 90, and 120 seconds, respectively. They concluded that these movements could be easily managed with a combination of manual couch movements and adjustment by the robotic arm. As noted earlier, the clinical impact of these displacements and resultant adjustments in treatments needs to be explored in much greater detail.
Noel et al. published data showing that intermittent target tracking is more sensitive than pre- and post-treatment target tracking to assess intra-fraction prostate motion, but to reach sufficient sensitivity, intermittent imaging must be performed at a high sampling rate. (8) They concluded that this supports the value of continuous real-time tracking. While this may be true, there is a major gap in the literature addressing the actual consequences of organ motion during radiation therapy. Li and colleagues analyzed data from 1,267 tracking sessions from 35 patients to look at the dosimetric consequences on intra-fraction organ motion during radiation therapy. (9) Results showed that even for the patients showing the largest overall movement, the prostate uniform equivalent dose was reduced by only 0.23%, and the minimum prostate dose remained over 95% of the nominal dose. When margins of 2 mm were used, the equivalent uniform dose was reduced by 0.51%, but sparing of the rectum and bladder was significantly reduced using the smaller margins. This study did not report on clinical outcomes, and data from a larger randomized cohort will be needed to verify these results.
In a clinical study, Kupelian et al. described differences found in radiation therapy sessions performed on 35 patients with prostate cancer. (10) In this paper, 6 of the initial 41 patients could not be studied because body habitus (A-P dimension) was too large to allow imaging. The results showed good agreement with x-ray localization. Displacements of 3 mm or more and 5 mm or more for cumulative duration of at least 30 seconds were observed during 41% and 15% of radiation sessions, respectively. The clinical sites for the study developed individualized protocols for responding to observed intra-fraction motion. This publication did not report on clinical implications or clinical outcomes, either for control of disease or treatment complications, e.g., proctitis. The clinical impact of these displacements and resultant adjustments in treatments needs to be explored in much greater detail.
Langen and colleagues reported on 17 patients treated at one of the centers in the study noted in the preceding paragraph. (11) In this study, overall, the prostate was displaced by greater than 3 mm in 13.6% of treatment time and by greater than 5 mm in 3.3% of treatment time. Results for median treatment time instead of mean were 10.5% and 2.0%, respectively. Again, the clinical impact of this movement was not determined. The authors did comment that potential clinical impact would depend on a number of factors including the clinical target volume (CTV). In this small series, intra-fraction movement did not change a large degree during treatment. However, the likelihood of displacement did increase as time elapsed after positioning.
No relevant outcome studies have been published in the literature for any site including, but not limited to, prostate, lung, and breast. Additionally, there are few registered clinical trials of these techniques at this time, and none of a randomized design focused on showing how these additional procedures may improve clinical outcomes, including a decrease in toxicity to surrounding tissue.
Because real-time intra-fraction target tracking generally uses IMRT to deliver radiation therapy, the use of real-time tracking is unlikely to produce outcomes that are inferior to IMRT treatment. Thus, on this basis, the real-time tracking approach is not considered to be investigational. However, there are no data that indicate that use of real-time tracking during radiation therapy to adjust the intra-fraction dose of radiation therapy or monitor target motion during radiation treatment improves clinical outcomes over existing techniques. In summary, because this technology is more costly than alternative services that produce equivalent therapeutic results, this is considered not medically necessary.
The policy was updated with a search of the MEDLINE database from October 2009 through November 2010. The literature search did not identify any randomized trials of real-time intra-fraction target tracking. Studies continue to consist of case series and nonrandomized comparative studies.
Sandler and colleagues reported on 64 patients treated with IMRT for prostate cancer in the Assessing the Impact of Margin Reduction (AIM) study. (12) Patients were implanted with Beacon transponders (Calypso Medical Technologies, Inc., Seattle, WA) and were treated with IMRT to a nominal dose of 81 Gy in 1.8 Gy fractions. Patients in this study were treated with reduced tumor margins, as well as real-time tumor tracking. Patient-reported morbidity associated with radiotherapy was the primary outcome. Study participants were compared to historic controls. Study participants reported fewer treatment-related symptoms and/or worsening of symptoms after treatment than the comparison group. For example, the percentage of patients in the historic comparison group reporting rectal urgency increased from 3% pre-treatment to 22% post-treatment, no increase was observed in the current experimental group.
With no randomized trials that compare IMRT with real-time intra-fraction target tracking to IMRT alone, it is not known whether the addition of real-time intra-fraction target tracking improves net heath outcome (fewer adverse effects and/or improved survival). Thus, the policy statement remains unchanged; this is considered not medically necessary.
Technology Assessments, Guidelines, and Position Statements
The current National Comprehensive Cancer Network (NCCN) guidelines for prostate cancer (v.3.2010) do not mention the use of real-time intra-fraction target tracking or the specific use of the Calypso 4D Localization System. (13)