Proton Accelerated Partial Breast Irradiation: Clinical Outcomes at a Planned Interim Analysis of a Prospective Phase 2 Trial

Published:September 15, 2020DOI:


      To perform a planned interim analysis of acute (within 12 months) and late (after 12 months) toxicities and cosmetic outcomes after proton accelerated partial breast irradiation (APBI).

      Methods and Materials

      A total of 100 patients with pTis or pT1-2 N0 (≤3cm) breast cancer status after segmental mastectomy were enrolled in a single-arm phase 2 study from 2010 to 2019. The clinically determined postlumpectomy target volume, including tumor bed surgical clips and operative-cavity soft-tissue changes seen on imaging plus a radial clinical expansion, was irradiated with passively scattered proton APBI (34 Gy in 10 fractions delivered twice daily with a minimum 6-hour interfraction interval). Patients were evaluated at protocol-specific time intervals for recurrence, physician reports of cosmetic outcomes and toxicities, and patient reports of cosmetic outcomes and satisfaction with the treatment or experience.


      Median follow-up was 24 months (interquartile range [IQR], 12-43 months). Local control and overall survival were 100% at 12 and 24 months. There were no acute or late toxicities of grade 3 or higher; no patients experienced fat necrosis, fibrosis, infection, or breast shrinkage. Excellent or good cosmesis at 12 months was reported by 91% of patients and 94% of physicians; at the most recent follow-up, these were 94% and 87%, respectively. The most commonly reported late cosmetic effect was telangiectasis (17%). The total patient satisfaction rate for treatment and results at 12 and 24 months was 96% and 100%, respectively. Patients’ mean time away from work was 5 days (IQR, 2-5 days), and the median out-of-pocket cost was $700 (IQR, $100-$1600). The mean left-sided heart dose was 2 cGy (range, 0.2-75 cGy), and the mean ipsilateral lung dose was 19 cGy (range, 0.2-164 cGy).


      Proton APBI is a maturing treatment option with high local control, favorable intermediate-term cosmesis, high treatment satisfaction, low treatment burden, and exceptional heart and lung sparing.
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        • Fisher B.
        • Anderson S.
        • Bryant J.
        • et al.
        Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer.
        N Engl J Med. 2002; 347: 1233-1241
        • Veronesi U.
        • Cascinelli N.
        • Mariani L.
        • et al.
        Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer.
        N Engl J Med. 2002; 347: 1227-1232
        • Sher D.J.
        • Wittenberg E.
        • Suh W.W.
        • Taghian A.G.
        • Punglia R.S.
        Partial-breast irradiation versus whole-breast irradiation for early-stage breast cancer: a cost-effectiveness analysis.
        Int J Radiat Oncol Biol Phys. 2009; 74: 440-446
        • Livi L.
        • Meattini I.
        • Marrazzo L.
        • et al.
        Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial.
        Eur J Cancer. 2015; 51: 451-463
        • Whelan T.J.
        • Julian J.A.
        • Berrang T.S.
        • et al.
        External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node-negative breast cancer (RAPID): a randomised controlled trial.
        Lancet. 2019; 394: 2165-2172
        • Vicini F.A.
        • Cecchini R.S.
        • White J.R.
        • et al.
        Long-term primary results of accelerated partial breast irradiation after breast-conserving surgery for early-stage breast cancer: a randomised, phase 3, equivalence trial.
        Lancet. 2019; 394: 2155-2164
        • Tann A.W.
        • Hatch S.S.
        • Joyner M.M.
        • Wiederhold L.R.
        • Swanson T.A.
        Accelerated partial breast irradiation: past, present, and future.
        World J Clin Oncol. 2016; 7: 370-379
        • Moon S.H.
        • Shin K.H.
        • Kim T.H.
        • et al.
        Dosimetric comparison of four different external beam partial breast irradiation techniques: three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, helical tomotherapy, and proton beam therapy.
        Radiother Oncol. 2009; 90: 66-73
        • Fogliata A.
        • Bolsi A.
        • Cozzi L.
        Critical appraisal of treatment techniques based on conventional photon beams, intensity modulated photon beams and proton beams for therapy of intact breast.
        Radiother Oncol. 2002; 62: 137-145
        • Wang X.
        • Amos R.A.
        • Zhang X.
        • et al.
        External-beam accelerated partial breast irradiation using multiple proton beam configurations.
        Int J Radiat Oncol Biol Phys. 2011; 80: 1464-1472
        • Galland-Girodet S.
        • Pashtan I.
        • MacDonald S.M.
        • et al.
        Long-term cosmetic outcomes and toxicities of proton beam therapy compared with photon-based 3-dimensional conformal accelerated partial-breast irradiation: a phase 1 trial.
        Int J Radiat Oncol Biol Phys. 2014; 90: 493-500
        • Kozak K.R.
        • Smith B.L.
        • Adams J.
        • et al.
        Accelerated partial-breast irradiation using proton beams: initial clinical experience.
        Int J Radiat Oncol Biol Phys. 2006; 66: 691-698
        • Bush D.A.
        • Do S.
        • Lum S.
        • et al.
        Partial breast radiation therapy with proton beam: 5-year results with cosmetic outcomes.
        Int J Radiat Oncol Biol Phys. 2014; 90: 501-505
        • Chang J.H.
        • Lee N.K.
        • Kim J.Y.
        • et al.
        Phase II trial of proton beam accelerated partial breast irradiation in breast cancer.
        Radiother Oncol. 2013; 108: 209-214
        • Strom E.A.
        • Amos R.A.
        • Shaitelman S.F.
        • et al.
        Proton partial breast irradiation in the supine position: treatment description and reproducibility of a multibeam technique.
        Pract Radiat Oncol. 2015; 5: e283-e290
        • Bekelman J.E.
        • Sylwestrzak G.
        • Barron J.
        • et al.
        Uptake and costs of hypofractionated vs conventional whole breast irradiation after breast conserving surgery in the United States, 2008-2013.
        JAMA. 2014; 312: 2542-2550
        • Ovalle V.
        • Strom E.A.
        • Godby J.
        • et al.
        Proton partial-breast irradiation for early-stage cancer: is it really so costly?.
        Int J Radiat Oncol Biol Phys. 2016; 95: 49-51
        • Albuquerque K.
        • Tell D.
        • Lobo P.
        • Millbrandt L.
        • Mathews H.L.
        • Janusek L.W.
        Impact of partial versus whole breast radiation therapy on fatigue, perceived stress, quality of life and natural killer cell activity in women with breast cancer.
        BMC Cancer. 2012; 12: 251
        • Oladeru O.T.
        • Yang D.D.
        • Miccio J.A.
        • Ma S.J.
        • Orio III, P.F.
        Declining use of brachytherapy as a modality of accelerated partial breast irradiation in the United States: a study of the National Cancer Database (2006-2015).
        Brachytherapy. 2018; 17: S48
        • Smith G.L.
        • Xu Y.
        • Buchholz T.A.
        • et al.
        Association between treatment with brachytherapy vs whole-breast irradiation and subsequent mastectomy, complications, and survival among older women with invasive breast cancer.
        JAMA. 2012; 307: 1827-1837
        • Silverstein M.J.
        • Fastner G.
        • Maluta S.
        • et al.
        Intraoperative radiation therapy: a critical analysis of the ELIOT and TARGIT trials. Part 2—TARGIT.
        Ann Surg Oncol. 2014; 21: 3793-3799
        • Shah C.
        • Vicini F.
        • Shaitelman S.F.
        • et al.
        The American Brachytherapy Society consensus statement for accelerated partial-breast irradiation.
        Brachytherapy. 2018; 17: 154-170
        • Correa C.
        • Harris E.E.
        • Leonardi M.C.
        • et al.
        Accelerated partial breast irradiation: executive summary for the update of an ASTRO evidence-based consensus statement.
        Pract Radiat Oncol. 2017; 7: 73-79
        • White J.R.
        • Winter K.
        • Cecchini R.S.
        • et al.
        Cosmetic outcome from post lumpectomy whole breast irradiation (WBI) versus partial breast irradiation (PBI) on the NRG Oncology/NSABP B39-RTOG 0413 phase III clinical trial.
        Int J Radiat Oncol Biol Phys. 2019; 105: S3-S4
        • Bush D.A.
        • Slater J.D.
        • Garberoglio C.
        • Do S.
        • Lum S.
        • Slater J.M.
        Partial breast irradiation delivered with proton beam: results of a phase II trial.
        Clin Breast Cancer. 2011; 11: 241-245
        • Rossi A.M.
        • Nehal K.S.
        • Lee E.H.
        Radiation-induced breast telangiectasias treated with the pulsed dye laser.
        J Clin Aesthet Dermatol. 2014; 7: 34-37
        • Shaitelman S.F.
        • Kim L.H.
        • Grills I.S.
        • et al.
        Predictors of long-term toxicity using three-dimensional conformal external beam radiotherapy to deliver accelerated partial breast irradiation.
        Int J Radiat Oncol Biol Phys. 2011; 81: 788-794
        • Hepel J.T.
        • Tokita M.
        • MacAusland S.G.
        • et al.
        Toxicity of three-dimensional conformal radiotherapy for accelerated partial breast irradiation.
        Int J Radiat Oncol Biol Phys. 2009; 75: 1290-1296
        • Essers M.
        • Osman S.O.
        • Hol S.
        • Donkers T.
        • Poortmans P.M.
        Accelerated partial breast irradiation (APBI): are breath-hold and volumetric radiation therapy techniques useful?.
        Acta Oncol. 2014; 53: 788-794
        • Qiu J.J.
        • Chang Z.
        • Horton J.K.
        • Wu Q.R.
        • Yoo S.
        • Yin F.F.
        Dosimetric comparison of 3D conformal, IMRT, and V-MAT techniques for accelerated partial-breast irradiation (APBI).
        Med Dosim. 2014; 39: 152-158
        • Stelczer G.
        • Major T.
        • Meszaros N.
        • Polgar C.
        • Pesznyak C.
        [Dosimetric comparison of different techniques for external beam accelerated partial breast irradiation].
        Magy Onkol. 2016; 60: 305-311
        • 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
        • Grantzau T.
        • Thomsen M.S.
        • Vaeth M.
        • Overgaard J.
        Risk of second primary lung cancer in women after radiotherapy for breast cancer.
        Radiother Oncol. 2014; 111: 366-373
        • Flejmer A.M.
        • Nyström P.W.
        • Dohlmar F.
        • Josefsson D.
        • Dasu A.
        Potential benefit of scanned proton beam versus photons as adjuvant radiation therapy in breast cancer.
        Int J Part Ther. 2015; 1: 845-855


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