Abstract
PURPOSE:
To evaluate trends in fractionation and cost of radiation for bone metastasis during a time period of multiple national quality improvement initiatives that focused on reducing the number of fractions per radiation episode.
METHODS:
Using nationwide Medicare claims from 2011 to 2014, we identified radiation episodes for bone metastasis from prostate, lung, and breast cancer. Details regarding fractionation, radiation therapy (RT) modality, and sociodemographic characteristics were abstracted from claims. Time trends in use of 10 or fewer RT fractions per episode were evaluated using the Cochran-Armitage test. Total cost per episode was calculated from a payer’s perspective and reported in 2017 dollars; time trends in cost were assessed using linear regression. Generalized linear models identified predictors of treatment with 10 or fewer fractions.
RESULTS:
Of 51,533 episodes identified, 46,326 used 2D/3D RT, 3,199 used intensity-modulated RT, and 2,008 used stereotactic body RT. The proportion of 2D/3D RT episodes using 10 or fewer fractions increased from 65.5% to 79.7% (Ptrend < .001), and mean total cost per episode decreased from $6,742 to $6,067 (Ptrend < .001). Use of single-fraction radiation increased modestly for 2D/3D treatment (6.5% to 8.1%; Ptrend < .001). Predictors of 10 or fewer fractions included treatment in recent years, advanced age (≥ 85 years), and higher comorbidity score. Variation was noted based on geographic region and primary cancer.
CONCLUSION:
During a period with quality initiatives launched by the American Society for Radiation Oncology, American Board of Internal Medicine, and National Quality Forum, use of 10 or fewer fractions for bone metastasis increased by 14.2%, but single-fraction regimens increased by only 1.6%, highlighting opportunities for quality improvement.
INTRODUCTION
A significant portion of patients with cancer will develop bony metastatic disease within their lifetime, with palliative radiotherapy representing a treatment that can mitigate symptoms and improve quality of life.1 However, improving the quality of life for patients with metastatic disease requires balancing the benefits of palliative radiation with its demands, specifically its cost, adverse effects, and time spent away from home. To address this need, a large body of literature has grown, which has demonstrated that shorter radiation schedules, even a single fraction, can yield pain control similar to longer regimens without increasing adverse effects.2,3
Yet, despite this literature, considerable variation in radiation therapy practice patterns for bone metastasis has long existed, with many patients historically treated on schedules that can reach up to 4 or more weeks (≥ 20 fractions). For example, an international survey of 962 radiation oncologists conducted in 2009 assessed treatment approaches for five hypothetical patients with bone metastasis and found use of more than 100 different dose-fractionation regimens, highlighting the need for standardized treatment recommendations.4 In response, the American Society for Radiation Oncology (ASTRO) released a bone metastasis clinical practice guideline in 2011 that recommended using treatment courses of 10 or fewer fractions.5 These sentiments were later amplified by the 2012 National Quality Forum Bone Metastasis Measure, which recommended regimens of one, five, six, or 10 fractions and were further endorsed by the 2013 Choosing Wisely Campaign of the American Board of Internal Medicine, which was supported by ASTRO.6,7 ASTRO also recommended that stereotactic body radiation therapy (SBRT), although promising, be limited primarily to the clinical trial setting.
However, despite these considerable efforts on a national level to reduce the number of delivered radiation treatments and thereby improve and standardize care for bone metastasis, relatively little is known about their impact, because most recent published series have focused on single-institutional efforts to increase use of single-fraction regimens.8-12 Understanding the impact of these efforts is vitally important to improve and promote value in cancer care. To address this knowledge gap, we used comprehensive national Medicare data including individuals with incident and prevalent breast, lung, and prostate cancer to identify episodes of radiation therapy for bone metastasis administered from 2011 to 2014. We evaluated whether fractionation and cost of radiation therapy for bone metastasis changed during this time interval and also characterized predictors of fractionation and survival after treatment.
METHODS
Study Cohort and Defining Treatment Episodes
We used the national fee-for-service Medicare claims data inclusive of patients with both incident and prevalent prostate, lung, and breast cancer from 2011 to 2014 with continuous part A and B fee-for-service coverage. From this data set, we identified all patient claims indicating treatment with radiation for a coded diagnosis of secondary malignant neoplasm of bone or bone marrow (International Classification of Diseases [9th revision, clinical modification]; ICD9 198.5).
From this patient population, we then defined individual treatment episodes from date of first radiation treatment through the last delivered radiation treatment. In concordance with prior literature, if an interval of 14 days or more occurred between delivery of radiation treatments, these were considered two separate treatment episodes.13 We then selected for those episodes with treatment start dates between July 1, 2011, and November 30, 2014, in which patients were at least 66 years of age or older and received outpatient 2D/3D conformal treatment, intensity-modulated radiation therapy (IMRT), or SBRT; Tables A1-A3).
Covariables
Episode-level covariables extracted from Medicare enrollment files included age, race, geographic region,14 primary diagnosis, and episode year and quarter. A modified Charlson comorbidity index was determined for each episode using the 6 months of claims preceding the start of the episode.15
Outcomes
The primary outcome was the number of fractions of external beam radiation per episode. Based on the existing literature, three different definitions of shorter fractionation regimens were used: (1) 10 fractions or fewer versus 11 fractions or more (consistent with the Choosing Wisely Initiative); (2) one, five, six, or 10 fractions versus not one, five, six, or 10 fractions (consistent with the National Quality Forum measure);and (3) single fraction versus multifraction (consistent with various single-institution quality improvement articles).2,6,7,12,16,17 Fraction number was calculated for outpatient radiation therapy episodes only, because the structure of the inpatient claims data precluded accurate measurement of the number of delivered fractions.
Secondary outcomes included type of radiation modality, episode total costs, and overall survival. Claims classified radiation modality as 2D or 3D conformal radiation, IMRT, or SBRT. Episode total costs were calculated for outpatient episodes only and were calculated from a payer perspective, inclusive of all Medicare costs from 14 days before the start of the episode (to capture radiation simulation and planning charges) through the last day of the episode. Payments were adjusted for inflation using the medical care component of the Consumer Price Index.18 Survival at 30 days, 1 year, and 2 years was calculated from the date of episode completion using the Kaplan-Meier method.
Statistical Analysis
We compared baseline differences in fractionation regimens by radiation treatment modality using χ2 tests. Time trends for use of shorter fractionation regimens by calendar year quarter were evaluated using the Cochran-Armitage test for trend. Time trends in cost by calendar year quarter were evaluated using linear regression. Generalized linear models (proc genmod in SAS; SAS Institute, Cary, NC) that accounted for the fact that episodes were nested within patients were implemented for each definition of shorter fractionation to discern independent predictors for shorter fractionation regimens versus other regimens. Variables were entered in a stepwise fashion and retained in the final model at a significance threshold of .05. Because the rate of shorter fractionation was greater than 10% and thus deemed not rare, results were expressed as risk ratios (RRs) and 95% CIs.19 Differences in overall survival by fractionation and radiation modality were compared using the log-rank test.
All statistical analyses were two-tailed and conducted using SAS 9.3, with a P value .05 or less considered statistically significant. This work was approved by our institutional review board and the Centers for Medicare & Medicaid Services Privacy Board.
RESULTS
Episode Characteristics and Practice Patterns
A total of 51,533 episodes of radiation for bone metastasis, inclusive of 41,214 unique patients, were identified. Median age at episode start was 75 years (interquartile range [IQR], 71 to 81 years). Lung cancer contributed to the greatest proportion of treatment episodes (40%; n = 20,609), followed by prostate cancer (36.1%; n = 18,587) and breast cancer (23.9%; n = 12,337), with 2D/3D conformal radiation therapy the most commonly used treatment modality (89.9%; n = 46,326; Table 1 and Tables A1 and A2). Of non-SBRT episodes, mean number of fractions was 9.7 overall, with 64.1% (n = 31,767) of episodes using 10 or fewer fractions; 46.3% (n = 22,909) of episodes using one, five, six, or 10 fractions; and 6.5% (n = 3,237) of episodes using a single radiation fraction. By modality, mean number of fractions per episode was 9.6 ± 5.2 for episodes when a 2D/3D radiation technique was used and 13.2 ± 8.6 for episodes when IMRT was used (P < .001; Fig A1).
TABLE 1.
Baseline Outpatient Episode Characteristics and General Practice Patterns (N = 51,533)
Trends in Adoption of Shorter Fractionation Schedules by Radiation Modality
Among 2D/3D conformal episodes, 68% (n = 46,326) used 10 or fewer fractions; 48% (n = 31,625) used one, five, six, or 10 fractions; and 6.8% (n = 3,140) used a single radiation fraction. From 2011 quarter (Q) 3 to 2014 Q4, use of shorter radiation fractionation schedules increased for each definition: for 10 or fewer fractions, from 65.5% to 79.7% (Ptrend < .001); for one, five, six, or 10 fractions, from 41.4% to 51.0% (Ptrend < .001); for a single fraction, from 6.5% to 8.1% (Ptrend < .001; Fig 1; Table A4).
Fig 1.
Fractionation and cost of outpatient treatment episodes. Quarterly utilization rates of three definitions of shorter radiation fractionation (≤ 10 fractions [fx]; one, five, six, and 10 fractions; and single fraction) demonstrated increased use over time. (A) Use of 2D/3D conformal radiation regimens of 10 or fewer fractions demonstrated a 14.2% increase in use (from 65.5% to 79.7%) over time. The 10 or fewer fraction regimen increased at a greater rate compared with the one-, five-, six-, and 10-fraction or single-fraction regimens. Average total cost per quarter decreased (from $6,742 to $6,067). All results were significant to P < .001. (B) Use of intensity-modulated radiation therapy (IMRT) regimens of 10 or fewer fractions and one, five, six, and 10 fractions increased over time versus single fractions (P < .001). Average total cost per quarter significantly decreased over time (from $12,933 to $10,514; P = .003). Q, quarter; RT, radiation therapy.
Among IMRT episodes, 44.6% (n = 1,427) used 10 or fewer fractions; 25.9% (n = 828) used one, five, six, or 10 fractions; and 3% (n = 97) used a single radiation fraction. From 2011 Q3 to 2014 Q4, use of shorter radiation fractionation schedules significantly increased for one, five, six, or 10 fractions, from 22.9% to 28.8% (P < .001). No significant utilization trends were found for the use of 10 or fewer fractions (from 46.1% to 63.4%; P = .10) or for single-fraction IMRT (from 5.6% in 2011 Q3 to 4.6% in 2014 Q3; P = .80; Fig 1; Table A4).
Clinical Predictors of Shorter Fractionation Schedules
Multivariable models for each outcome of shorter fractionation regimens are listed in Table 2. Compared with 2D/3D conformal treatments, IMRT episodes were significantly less likely to use any of the three shorter fractionation regimens. For example, for the 10 or fewer fractions outcome definition, IMRT was associated with an RR of 0.66 (95% CI, 0.64 to 0.69; P < .001; referent, 2D/3D). For the 10 or fewer fractions definition, those associated with a higher likelihood of shorter fractionation included age 85 years or older (RR = 1.06; 95% CI, 1.03 to 1.08; P < .001), Charlson comorbidity score of 2 or higher (RR = 1.05; 95% CI, 1.03 to 1.06; P < .001), and treatment in later years (eg, 2014 v 2011: RR = 1.11; 95% CI, 1.09 to 1.13; P < .001). Female patients with breast cancer were significantly less likely to receive 10 or fewer fractions (RR = 0.96; 95% CI, 0.94 to 0.98; P < .001) compared with male patients with prostate cancer. In addition, treatment episodes within the New England, East and West North Central, Mountain, and Pacific regions were significantly more likely to use 10 or fewer fractions relative to the South Atlantic region. Findings were qualitatively similar for the other two definitions of shorter fractionation.
TABLE 2.
A Multivariable Analysis of 2012 to 2014 Outpatient Radiation Episodes and Predictive Variables for Determining Delivered Fractionation Regimens
Cost by Modality and Fractionation Regimens
Mean total health care cost of a 2D/3D radiation episode was $6,534 (IQR, $4,109 to $7,895), compared with $11,719 (IQR, $7,287 to $14,517) for an IMRT episode and $12,669 (IQR, $8,269 to $15,794) for an SBRT episode (Table 3). The average total cost per radiation episode of 2D/3D conformal radiation and IMRT is depicted in Figure 1. Quarterly trends demonstrated a significant decline in mean total episode cost over time. For example, cost of a 2D/3D episode decreased from $6,742 in 2011 Q3 to $6,067 in 2014 Q4 (P < .001) and for an IMRT episode, decreased from $12,933 to $10,514 (P < .001).
TABLE 3.
2012-2014 Outpatient Total Costs and Mortality Outcomes by Radiation Fractionation Regimens
In addition, comparison of average total cost by fractionation regimens demonstrates a lower average total cost and a greater cost differential between the reduced fractionation regimen and its counterpart (Table 3). For example, the average total cost of a 2D/3D 10-or fewer fraction regimen is $5,535 and represents $3,203 in savings versus an 11 or greater-fraction regimen. In contrast, the average total cost of a one-, five-, six-, or 10-fraction regimen is $5,759, which differs by $1,510 from fractionation regimens that did not use one, five, six, or 10 fractions. These findings are also seen when assessing cost for IMRT fractionation regimens.
Treatment Patterns Related to Survival Outcomes
Median survival after completion of radiation was 0.50 years (IQR, 0.17 to 1.37 years) after a 2D/3D episode, 0.79 years (IQR, 0.29 to 1.83) after an IMRT episode, and 0.80 years (IQR, 0.0.27 to 1.78 years) after an SBRT episode (P < .001). Receipt of 2D/3D conformal radiation correlated with significantly lower 30-day, 1-year, and 2-year survival rates compared with IMRT or SBRT. This was consistent across all three shortened fractionation definitions (P < .001). Delivery of shorter fractionation regimens correlated with decreased median survival, particularly using the 10 or fewer fraction and single-fraction definitions of shorter fractionation. For example, treatment with 10 or fewer fractions of 2D/3D radiation therapy was associated with a median survival of 0.42 years versus 0.70 years for 11 or more fractions and 0.26 years for a single fraction versus 0.53 years for two or more fractions.
Furthermore, although 2-year survival rates were low, a subset of survivors was noted in each of the 2D/3D conformal, IMRT, and SBRT groups (17%, 23%, and 24%, respectively). Single-fraction episodes had the lowest 2-year survival rates (10% for 2D/3D conformal, 15% for IMRT, and 22% for SBRT). Additional details are listed in Table 3.
DISCUSSION
In this nationally comprehensive, population-based study of 51,533 radiation episodes for bone metastasis, we noted significant increase in use of shorter fractionation regimens accompanied by cost reduction. From 2011 to 2014, use of 10 or fewer fractions of 2D/3D radiation to treat bone metastasis increased by 14.2%, and cost per episode decreased by $675. Similarly, use of 10 or fewer fractions of IMRT to treat bone metastasis increased by 17.3%, and cost per episode decreased by $2,419. Single-fraction 2D/3D radiation also significantly increased from 6.5% to 8.1%. Conservatively, we estimate these changes resulted in a yearly cost reduction to Medicare on the order of tens of millions of dollars. These results highlight two important findings: (1) there are clinically meaningful secular trends toward improved quality in palliative treatment of bone metastasis, and (2) despite multiple guidelines that support single-fraction treatment, only a modest increase in utilization has occurred.
These findings coincide with efforts throughout medicine to improve the quality of treatment delivery by minimizing overuse of unnecessary medical procedures and treatments.20 For cancer care, one such focus has been shortening the duration of palliative radiation for bone metastasis as advocated by the ASTRO Bone Metastasis Guideline, National Quality Forum Bone Metastasis Measure, and American Board of Internal Medicine Choosing Wisely Campaign.5-7 Furthermore, although these guidelines provide flexibility in treatment regimens, they also suggest use of single-fraction regimens when clinically appropriate.
However, although we were able to demonstrate trends toward shorter fractionation, we see only a modest increase in single-fraction use. It is unclear why American radiation oncologists are hesitant to adopt these policies,21 but our findings indicate there is room for continued improvement. From a value-based standpoint, were more radiation oncologists to use single-fraction treatments when appropriate, this could improve the quality of palliative radiotherapy within the United States.
Specific factors associated with use of fewer radiation fractions include use of 2D/3D conformal radiation, older age, advanced comorbidity, and certain cancer histologies or geographic treatment regions. With regard to patient-based predictors, our findings indicate that physicians were more inclined to provide shorter treatment schedules to patients they perceived to have a shorter life expectancy. This intriguing finding suggests that, on average, radiation oncologists do attempt to calibrate their treatment recommendations according to anticipated survival, a key principal advocated in palliative medicine and geriatric oncology. As encouraged by the Choosing Wisely statements, older age and advanced comorbidity had the greatest influence using the single-fraction definition of shorter fractionation, whereas other patients could be considered for more aggressive treatments. These findings are also consistent with prior studies, which have demonstrated a disproportionate use of palliative radiation, including single-fraction treatments, for those patients closer to death.22,23
Interestingly, geographic region was also associated with duration of radiation treatment, with shorter courses more common in the New England, Mountain, Pacific, and East and West North Central regions relative to the South Atlantic region. The reasons for this geographic difference are unclear, but one such explanation could be a spillover effect from the adoption of dedicated palliative radiation oncology services in these regions.8,9,17,24
Although our findings indicate progress in delivery of palliative radiation, they also indicate that a one-size-fits-all approach is not necessarily achievable in this setting. As shown in Table 1, although 2D/3D radiation treatments encompassed almost 90% of radiation episodes and demonstrated consistent improvement, IMRT treatments were more likely to use extended fractionation regimens. In addition, radiation oncologists seemed to reserve IMRT for patients whom they perceived to have increased longevity. SBRT trends were less discernable but use increased over time, indicating the growing interests in exploring the higher biologically effective dose of SBRT versus 2D/3D conformal radiation and its associated palliative benefits (Table A5).25 We hypothesize that these differences stem from more complicated clinical presentations, such as sensitive anatomical sites, areas of re-irradiation, or in patients anticipated to be long-term survivors in whom a durable local control response is ideal. Our data underscore that a nontrivial fraction (10% to 22%) of patients remain alive 2 years after completing radiation for bone metastasis, which indicates that choices regarding dose-fractionation for these patients must consider goals such as long-term local control of the radiated metastasis and mitigation of late radiation toxicity.
The strengths of this analysis include its large-scale, encompassing national utilization patterns and outcomes. However, certain limitations exist. For example, we could not delineate specific radiation details, such as site and number of bone metastases; areas of new treatment versus retreatment; incomplete radiation courses; radiation intent for pain, pathologic fracture, or neurologic compromise; or bone metastasis claims without a diagnosis code of ICD9 198.5. Furthermore, because this was a Medicare-based analysis, treatment of patients younger than 66 years of age or those using private insurance or out-of-pocket payments are not reported. Inpatient assessment and data regarding proton use was limited and thus excluded from analysis. Lastly, given the contemporary period and use patterns, no causal link between the national guidelines mentioned and utilization trends can be concluded.
In summary, this study demonstrates important national trends in radiation for bone metastasis, namely, increasing use of shorter fractionation regimens with accompanying cost reduction. Nevertheless, single-fraction regimens increased only modestly, and overall use of single-fraction regimens remains less than 10%, suggesting opportunities for continued national quality improvement.
ACKNOWLEDGMENT
Supported in part by a grant from Varian Medical System (B.D.S.), National Institutes of Health, National Cancer Institute Grant No. R01 CA207216-01 (B.D.S., Y.-C.T.S., and S.H.G.), and The University of Texas MD Anderson Cancer Center under the Cancer Center Support Core Grant (CA16672). B.D.S. is supported by the Cancer Prevention & Research Institute of Texas (RP160674) and is an Andrew Sabin Family Fellow. S.H.G. is supported by Komen Grants No. SAC 150061 and CPRIT RP160674.
APPENDIX
Fig A1.
Outpatient palliative radiation episodes for bone metastasis from 2011 to 2014 are separated by treatment modality and fractionation (n = 49,525, including 2D/3D and intensity-modulated radiation therapy [IMRT] only). Among non–stereotactic body radiation therapy episodes, 64.1% (n = 31,767) of episodes used 10 or more fractions, 46.3% (n = 22,909) of episodes used one, five, six, or 10 fractions, and 6.5% (n = 3,237) of episodes used a single radiation fraction. By modality, the mean number of fractions per episode was 9.6 ± 5.2 for episodes when a 2D/3D radiation technique was used and 13.2 ± 8.6 for episodes when IMRT was used (P < .001). RT, radiation therapy
TABLE A1.
Flowchart of Cohort Creation: Patient Level
TABLE A2.
Flowchart of Cohort Creation: Episode Level
TABLE A3.
Inclusion and Exclusion Criteria Procedure and Diagnosis Codes
TABLE A4.
2011 to 2014 Fractionation Regimens and Cost by Treatment Modality
TABLE A5.
2011 to 2014 SBRT Fractionation Trends
AUTHOR CONTRIBUTIONS
Conception and design: Jennifer K. Logan, Benjamin D. Smith
Collection and assembly of data: Jennifer K. Logan, Benjamin D. Smith
Data analysis and interpretation: Jennifer K. Logan, Jing Jiang, Ya-Chen Tina Shih, Xiudong Lei, Ying Xu, Karen E. Hoffman, Sharon H. Giordano, Benjamin D. Smith
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Trends in Radiation for Bone Metastasis During a Period of Multiple National Quality Improvement Initiatives
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jop/site/ifc/journal-policies.html.
Ya-Chen Tina Shih
Research Funding: Novartis (Inst)
Karen E. Hoffman
Research Funding: Janssen (Inst)
Benjamin D. Smith
Research Funding: Varian Medical Systems
Patents, Royalties, Other Intellectual Property: Through my employer, I have an equity interest in Oncora Medical as part of a partnership agreement (Inst)
No other potential conflicts of interest were reported.
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