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Establishing Cost-Effective Allocation of Proton Therapy for Breast Irradiation

      Purpose

      Cardiac toxicity due to conventional breast radiation therapy (RT) has been extensively reported, and it affects both the life expectancy and quality of life of affected women. Given the favorable oncologic outcomes in most women irradiated for breast cancer, it is increasingly paramount to minimize treatment side effects and improve survivorship for these patients. Proton RT offers promise in limiting heart dose, but the modality is costly and access is limited. Using cost-effectiveness analysis, we provide a decision-making tool to help determine which breast cancer patients may benefit from proton RT referral.

      Methods and Materials

      A Markov cohort model was constructed to compare the cost-effectiveness of proton versus photon RT for breast cancer management. The model was analyzed for different strata of women based on age (40 years, 50 years, and 60 years) and the presence or lack of cardiac risk factors (CRFs). Model entrants could have 1 of 3 health states: healthy, alive with coronary heart disease (CHD), or dead. Base-case analysis assumed CHD was managed medically. No difference in tumor control was assumed between arms. Probabilistic sensitivity analysis was performed to test model robustness and the influence of including catheterization as a downstream possibility within the health state of CHD.

      Results

      Proton RT was not cost-effective in women without CRFs or a mean heart dose (MHD) <5 Gy. Base-case analysis noted cost-effectiveness for proton RT in women with ≥1 CRF at an approximate minimum MHD of 6 Gy with a willingness-to-pay threshold of $100,000/quality-adjusted life-year. For women with ≥1 CRF, probabilistic sensitivity analysis noted the preference of proton RT for an MHD ≥5 Gy with a similar willingness-to-pay threshold.

      Conclusions

      Despite the cost of treatment, scenarios do exist whereby proton therapy is cost-effective. Referral for proton therapy may be cost-effective for patients with ≥1 CRF in cases for which photon plans are unable to achieve an MHD <5 Gy.
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      References

        • US Cancer Statistics Working Group
        United States Cancer Statistics: 1999–2012 Incidence and Mortality Web-Based Report.
        Department of Health and Human Services, Centers for Disease Control and Prevention, and National Cancer Institute, Atlanta (GA)2015
      1. Howlader N, Noone AM, Krapcho M, eds. SEER cancer statistics review, 1975-2012, National Cancer Institute [based on November 2014 SEER data submission, posted to SEER Web site April 2015]. Bethesda, MD. Available at: http://seer.cancer.gov/csr/1975_2012/. Accessed September 1, 2015.

        • Hooning M.J.
        • Botma A.
        • Aleman B.M.
        • et al.
        Long-term risk of cardiovascular disease in 10-year survivors of breast cancer.
        J Natl Cancer Inst. 2007; 99: 365-375
        • Darby S.C.
        • Ewertz M.
        • McGale P.
        • et al.
        Risk of ischemic heart disease in women after radiotherapy for breast cancer.
        N Engl J Med. 2013; 368: 987-998
        • Formenti S.C.
        • DeWyngaert J.K.
        • Jozsef G.
        • et al.
        Prone vs supine positioning for breast cancer radiotherapy.
        JAMA. 2012; 308: 861-863
        • MacDonald S.M.
        • Patel S.A.
        • Hickey S.
        • et al.
        Proton therapy for breast cancer after mastectomy: Early outcomes of a prospective clinical trial.
        Int J Radiat Oncol Biol Phys. 2013; 86: 484-490
        • Smyth L.M.
        • Knight K.A.
        • Aarons Y.K.
        • et al.
        The cardiac dose-sparing benefits of deep inspiration breath-hold in left breast irradiation: A systematic review.
        J Med Radiat Sci. 2015; 62: 66-73
        • Peeters A.
        • Grutters J.P.
        • Pijls-Johannesma M.
        • et al.
        How costly is particle therapy? Cost analysis of external beam radiotherapy with carbon-ions, protons and photons.
        Radiother Oncol. 2010; 95: 45-53
        • Epstein K.
        Is spending on proton beam therapy for cancer going too far, too fast?.
        BMJ. 2012; 344: e2488
      2. Beck M. Big bets on proton therapy face uncertain future. The Wall Street Journal. May 26, 2015. Available at: http://www.wsj.com/articles/big-bets-on-proton-therapy-face-uncertain-future-1432667393. Accessed September 30, 2015.

        • Taylor C.
        • Wang Z.
        • Macaulay E.
        • et al.
        Exposure of the heart in breast cancer radiation therapy: A systematic review of heart doses published during 2003 to 2013.
        Int J Radiat Oncol Biol Phys. 2015; 93: 845-853
        • Sullivan P.W.
        • Ghushchyan V.
        Preference-based EQ-5D index scores for chronic conditions in the United States.
        Med Decis Making. 2006; 26: 410-420
        • Russell L.B.
        • Gold M.R.
        • Siegel J.E.
        • et al.
        The role of cost-effectiveness analysis in health and medicine. Panel on Cost-Effectiveness in Health and Medicine.
        JAMA. 1996; 276: 1172-1177
        • Eichler H.G.
        • Kong S.X.
        • Gerth W.C.
        • et al.
        Use of cost-effectiveness analysis in health-care resource allocation decision-making: How are cost-effectiveness thresholds expected to emerge?.
        Value Health. 2004; 7: 518-528
        • Siegel J.E.
        • Weinstein M.C.
        • Russell L.B.
        • et al.
        Recommendations for reporting cost-effectiveness analyses. Panel on Cost-Effectiveness in Health and Medicine.
        JAMA. 1996; 276: 1339-1341
        • Mailhot Vega R.B.
        • Kim J.
        • Bussière M.
        • et al.
        Cost effectiveness of proton therapy compared with photon therapy in the management of pediatric medulloblastoma.
        Cancer. 2013; 119: 4299-4307
        • Fraker Jr., T.D.
        • Fihn S.D.
        • 2002 Chronic Stable Angina Writing Committee
        • et al.
        2007 chronic angina focused update of the ACC/AHA 2002 guidelines for the management of patients with chronic stable angina: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to develop the focused update of the 2002 guidelines for the management of patients with chronic stable angina.
        J Am Coll Cardiol. 2007; 50: 2264-2274
      3. Bureau of Labor Statistics. Consumer price index (CPI) medical care. Washington, DC: US Department of Labor, Bureau of Labor Statistics. Available at: http://data.bls.gov/timeseries/CUUR0000SAM. Accessed October 18, 2013.

        • PDR Network
        Red Book: Pharmacy’s Fundamental Reference.
        PDR Network, Montvale, NJ2010
        • Feldman D.N.
        • Gade C.L.
        • Slotwiner A.J.
        • et al.
        Comparison of outcomes of percutaneous coronary interventions in patients of three age groups (<60, 60 to 80, and >80 years) (from the New York State Angioplasty Registry).
        Am J Cardiol. 2006; 98: 1334-1339
        • Arias E.
        United States life tables, 2009.
        Natl Vital Stat Rep. 2014; 62: 1-63
        • Jagsi R.
        • DeLaney T.F.
        • Donelan K.
        • et al.
        Real-time rationing of scarce resources: The Northeast Proton Therapy Center experience.
        J Clin Oncol. 2004; 22: 2246-2250
        • Sher D.J.
        Cost-effectiveness studies in radiation therapy.
        Expert Rev Pharmacoecon Outcomes Res. 2010; 10: 567-582
        • Nissen H.D.
        • Appelt A.L.
        Improved heart, lung and target dose with deep inspiration breath hold in a large clinical series of breast cancer patients.
        Radiother Oncol. 2013; 106: 28-32
        • Stranzl H.
        • Zurl B.
        Postoperative irradiation of left-sided breast cancer patients and cardiac toxicity. Does deep inspiration breath-hold (DIBH) technique protect the heart?.
        Strahlenther Onkol. 2008; 184: 354-358
        • Hayden A.J.
        • Rains M.
        • Tiver K.
        Deep inspiration breath hold technique reduces heart dose from radiotherapy for left-sided breast cancer.
        J Med Imaging Radiat Oncol. 2012; 56: 464-472
        • Swanson T.
        • Grills I.S.
        • Ye H.
        • et al.
        Six-year experience routinely using moderate deep inspiration breath-hold for the reduction of cardiac dose in left-sided breast irradiation for patients with early-stage or locally advanced breast cancer.
        Am J Clin Oncol. 2013; 36: 24-30
        • Stranzl H.
        • Zurl B.
        • Langsenlehner T.
        • et al.
        Wide tangential fields including the internal mammary lymph nodes in patients with left-sided breast cancer. Influence of respiratory-controlled radiotherapy (4D-CT) on cardiac exposure.
        Strahlenther Onkol. 2009; 185: 155-160
        • Lymberis S.C.
        • DeWyngaert J.K.
        • Parhar P.
        • et al.
        Prospective assessment of optimal individual position (prone versus supine) for breast radiotherapy: Volumetric and dosimetric correlations in 100 patients.
        Int J Radiat Oncol Biol Phys. 2012; 84: 902-909
        • Fagundes M.
        • Hug E.B.
        • Pankuch M.
        • et al.
        Proton therapy for local-regionally advanced breast cancer maximizes cardiac sparing.
        Int J Particle Ther. 2015; 1: 827-844
        • Ma J.
        • Li J.
        • Xi J.
        • et al.
        Post mastectomy linac IMRT irradiation of chest wall and regional nodes: Dosimetry data and acute toxicities.
        Radiat Oncol. 2013; 8: 81
        • Whelan T.J.
        • Olivotto I.A.
        • Parulekar W.R.
        • et al.
        Regional nodal irradiation in early-stage breast cancer.
        N Engl J Med. 2015; 373: 307-316
        • Poortmans P.M.
        • Collette S.
        • Kirkove C.
        • et al.
        Internal mammary and medial supraclavicular irradiation in breast cancer.
        N Engl J Med. 2015; 373: 317-327
        • Nilsson G.
        • Holmberg L.
        • Garmo H.
        • et al.
        Distribution of coronary artery stenosis after radiation for breast cancer.
        J Clin Oncol. 2012; 30: 380-386
        • Lundkvist J.
        • Ekman M.
        • Ericsson S.R.
        • et al.
        Economic evaluation of proton radiation therapy in the treatment of breast cancer.
        Radiother Oncol. 2005; 75: 179-185

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