5 fr Ultrahypofractionated WBI and SIB for Breast Cancer With Unfavorable Characteristics

NCT07020780 | Recruiting DMC

• 1 other identifier: HY FIVE
• Study Type: interventional
• Target: 458
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, randomized, single-center, non-inferiority interventional clinical trial comparing whole breast irradiation (WBI) to a total dose of 26 Gy in 5 fractions with simultaneous integrated boost (SIB) to the tumor bed to a total dose of 30 Gy, and WBI to a total dose of 40.05 Gy in 15 fractions with SIB to the tumor bed to a total dose of 48 Gy (standard treatment), for young or unfavorable breast cancer patients.

Conditions

Breast Cancer

Keywords

Breast Cancer; Whole Breast Irradiation; Simultaneous Integrated Boost; Adjuvant Radiotherapy; Utrahypofractionated Radiotherapy; Moderately Hypofractionated Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Local Relapse Free Survival (LRFS)

  o demonstrate the non-inferiority of local control (local relapse free survival - LRFS) of the study treatment (delivered in five fractions) compared to the department's standard WBI treatment (delivered in 15 fractions).

  5 years

Secondary Outcomes (21)

• Acute toxicity

  1 month

• Acute toxicity

  3 months

• Late toxicity

  5 years

• Late toxicity

  5 years

• Local Control

  5 years

Study Arms (2)

Arm 1- Five fractions radiotherapy

EXPERIMENTAL

Patients in the study (randomized to arm 1) will be treated to the whole breast to a total dose (TD) of 26 Gy in 5 fractions, with simultaneous integrated boost (SIB) to a TD of 30 Gy to the tumor bed. For each patient, an IMRT (intensity modulated radiotherapy) treatment plan will be created to ensure adequate coverage of the treatment volumes and the tolerability of the Organs At Risk (OAR). Specific, already validated dose-volume constraints will be applied for the evaluation of OARs. The dose-volume histogram (DVH) for the Gross Tumor Volume (GTV), Clinical Target Volume (CTV), PTV, and OAR will be calculated in order to achieve the best optimization in terms of tolerability and efficacy.

Radiation: Adjuvant 5 fractions whole breast irradiation with simultaneous integrated boost to the tumor bed

Arm 2- Fifteen fractions radiotherapy

ACTIVE COMPARATOR

Patients randomized to arm 2 will be treated according to the standard protocol of our department, delivering adjuvant whole breast irradiation (WBI) to a total dose (TD) of 40.05 Gy in 15 fractions, with simultaneous integrated boost (SIB) to the tumor bed to a TD of 48 Gy.

Radiation: Adjuvant 5 fractions whole breast irradiation with simultaneous integrated boost to the tumor bed

Interventions

Adjuvant 5 fractions whole breast irradiation with simultaneous integrated boost to the tumor bed RADIATION

Experimental arm (arm 1-five fractions WBI) patients will be treated to a total dose (TD) of 26 Gy in 5 fractions to whole breast, and a simultaneous integrated boost (SIB) to a TD of 30 Gy to the tumor bed, while arm 2-fifteen-fractions WBI patients with 40 Gy/15 fractions to PTV, and 48 Gy SIB to the tumor bed.

Also known as: Ultrahypofractionated WBI with SIB

Arm 1- Five fractions radiotherapy; Arm 2- Fifteen fractions radiotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Gender Eligibility Details: Female patients with breast cancer and age \<40 years regardless if histology, or 40-70 years old with unfavorable characteristics.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological diagnosis of breast cancer
• Patients younger than 40 years regardless of histological subtype, or patients between 40 and 70 years with lobular carcinoma, histological subtypes Luminal B Her2 positive, or with hormone receptors negative and Her2 positive (ErbB2), or triple negative (TNBC)
• Signed informed consent
• Clinical stage T1-T3, Nx-N3
• Negative surgical margins (≥ 0.2 cm)
• Clinical M0 in the previous 3 months
• PS (ECOG) ≤2
• No previous thoracic radiotherapy
• Fertile women using contraceptive methods started during oncological treatment

You may not qualify if:

• Patients with favorable characteristics (Luminal A, Luminal B Her2 negative, ≥ 40 years) undergoing partial irradiation
• Patients who have undergone mastectomy
• Multicentric tumors
• Positive or close surgical margins (\<0.2 cm)
• BRCA1/2 positive (only if known)
• Serious systemic diseases
• Mental or other disorders that may prevent the patient from signing the informed consent
• Previous invasive tumor, except skin cancer (excluding melanoma) unless the patient has been disease-free for at least 3 years (for example carcinoma in situ of the oral cavity or bladder)
• Collagen or autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, scleroderma, Sjogren's syndrome)
• Evidence of distant metastases (M1)
• Contraindication to treatment systemic
• Pregnant women
• Non-compliance with the dose limits established in the treatment plan

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

IRCCS San Raffaele Scientific Institute

Milan, 20132, Italy

RECRUITING

Related Publications (45)

• START Trialists' Group; Bentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett-Lee PJ, Bentzen SM, Bliss JM, Brown J, Dewar JA, Dobbs HJ, Haviland JS, Hoskin PJ, Hopwood P, Lawton PA, Magee BJ, Mills J, Morgan DA, Owen JR, Simmons S, Sumo G, Sydenham MA, Venables K, Yarnold JR. The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet. 2008 Mar 29;371(9618):1098-107. doi: 10.1016/S0140-6736(08)60348-7. Epub 2008 Mar 19.

  PMID: 18355913 RESULT

• Clark RM, Whelan T, Levine M, Roberts R, Willan A, McCulloch P, Lipa M, Wilkinson RH, Mahoney LJ. Randomized clinical trial of breast irradiation following lumpectomy and axillary dissection for node-negative breast cancer: an update. Ontario Clinical Oncology Group. J Natl Cancer Inst. 1996 Nov 20;88(22):1659-64. doi: 10.1093/jnci/88.22.1659.

  PMID: 8931610 RESULT

• Whelan TJ, Pignol JP, Levine MN, Julian JA, MacKenzie R, Parpia S, Shelley W, Grimard L, Bowen J, Lukka H, Perera F, Fyles A, Schneider K, Gulavita S, Freeman C. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med. 2010 Feb 11;362(6):513-20. doi: 10.1056/NEJMoa0906260.

  PMID: 20147717 RESULT

• Shaitelman SF, Lei X, Thompson A, Schlembach P, Bloom ES, Arzu IY, Buchholz D, Chronowski G, Dvorak T, Grade E, Hoffman K, Perkins G, Reed VK, Shah SJ, Stauder MC, Strom EA, Tereffe W, Woodward WA, Amaya DN, Shen Y, Hortobagyi GN, Hunt KK, Buchholz TA, Smith BD. Three-Year Outcomes With Hypofractionated Versus Conventionally Fractionated Whole-Breast Irradiation: Results of a Randomized, Noninferiority Clinical Trial. J Clin Oncol. 2018 Oct 31;36(35):JCO1800317. doi: 10.1200/JCO.18.00317. Online ahead of print.

  PMID: 30379626 RESULT

• Chua BH, Link EK, Kunkler IH, Whelan TJ, Westenberg AH, Gruber G, Bryant G, Ahern V, Purohit K, Graham PH, Akra M, McArdle O, O'Brien P, Harvey JA, Kirkove C, Maduro JH, Campbell ID, Delaney GP, Martin JD, Vu TTT, Muanza TM, Neal A, Olivotto IA; BIG 3-07/TROG 07.01 trial investigators. Radiation doses and fractionation schedules in non-low-risk ductal carcinoma in situ in the breast (BIG 3-07/TROG 07.01): a randomised, factorial, multicentre, open-label, phase 3 study. Lancet. 2022 Aug 6;400(10350):431-440. doi: 10.1016/S0140-6736(22)01246-6.

  PMID: 35934006 RESULT

• Meattini I, Becherini C, Boersma L, Kaidar-Person O, Marta GN, Montero A, Offersen BV, Aznar MC, Belka C, Brunt AM, Dicuonzo S, Franco P, Krause M, MacKenzie M, Marinko T, Marrazzo L, Ratosa I, Scholten A, Senkus E, Stobart H, Poortmans P, Coles CE. European Society for Radiotherapy and Oncology Advisory Committee in Radiation Oncology Practice consensus recommendations on patient selection and dose and fractionation for external beam radiotherapy in early breast cancer. Lancet Oncol. 2022 Jan;23(1):e21-e31. doi: 10.1016/S1470-2045(21)00539-8.

  PMID: 34973228 RESULT

• Marta GN, Coles C, Kaidar-Person O, Meattini I, Hijal T, Zissiadis Y, Pignol JP, Ramiah D, Ho AY, Cheng SH, Sancho G, Offersen BV, Poortmans P. The use of moderately hypofractionated post-operative radiation therapy for breast cancer in clinical practice: A critical review. Crit Rev Oncol Hematol. 2020 Dec;156:103090. doi: 10.1016/j.critrevonc.2020.103090. Epub 2020 Aug 26.

  PMID: 33091800 RESULT

• Wang SL, Fang H, Song YW, Wang WH, Hu C, Liu YP, Jin J, Liu XF, Yu ZH, Ren H, Li N, Lu NN, Tang Y, Tang Y, Qi SN, Sun GY, Peng R, Li S, Chen B, Yang Y, Li YX. Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer: a randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol. 2019 Mar;20(3):352-360. doi: 10.1016/S1470-2045(18)30813-1. Epub 2019 Jan 30.

  PMID: 30711522 RESULT

• Coles CE, Haviland JS, Kirby AM, Griffin CL, Sydenham MA, Titley JC, Bhattacharya I, Brunt AM, Chan HYC, Donovan EM, Eaton DJ, Emson M, Hopwood P, Jefford ML, Lightowlers SV, Sawyer EJ, Syndikus I, Tsang YM, Twyman NI, Yarnold JR, Bliss JM; IMPORT Trial Management Group. Dose-escalated simultaneous integrated boost radiotherapy in early breast cancer (IMPORT HIGH): a multicentre, phase 3, non-inferiority, open-label, randomised controlled trial. Lancet. 2023 Jun 24;401(10394):2124-2137. doi: 10.1016/S0140-6736(23)00619-0. Epub 2023 Jun 8.

  PMID: 37302395 RESULT

• Haviland JS, Bentzen SM, Bliss JM, Yarnold JR; START Trial Management Group. Prolongation of overall treatment time as a cause of treatment failure in early breast cancer: An analysis of the UK START (Standardisation of Breast Radiotherapy) trials of radiotherapy fractionation. Radiother Oncol. 2016 Dec;121(3):420-423. doi: 10.1016/j.radonc.2016.08.027. Epub 2016 Sep 22.

  PMID: 27666929 RESULT

• Lievens Y. Hypofractionated breast radiotherapy: financial and economic consequences. Breast. 2010 Jun;19(3):192-7. doi: 10.1016/j.breast.2010.03.003.

  PMID: 20511069 RESULT

• Marta GN, Ramiah D, Kaidar-Person O, Kirby A, Coles C, Jagsi R, Hijal T, Sancho G, Zissiadis Y, Pignol JP, Ho AY, Cheng SH, Offersen BV, Meattini I, Poortmans P. The Financial Impact on Reimbursement of Moderately Hypofractionated Postoperative Radiation Therapy for Breast Cancer: An International Consortium Report. Clin Oncol (R Coll Radiol). 2021 May;33(5):322-330. doi: 10.1016/j.clon.2020.12.008. Epub 2020 Dec 23.

  PMID: 33358283 RESULT

• FAST Trialists group; Agrawal RK, Alhasso A, Barrett-Lee PJ, Bliss JM, Bliss P, Bloomfield D, Bowen J, Brunt AM, Donovan E, Emson M, Goodman A, Harnett A, Haviland JS, Kaggwa R, Morden JP, Robinson A, Simmons S, Stewart A, Sydenham MA, Syndikus I, Tremlett J, Tsang Y, Wheatley D, Venables K, Yarnold JR. First results of the randomised UK FAST Trial of radiotherapy hypofractionation for treatment of early breast cancer (CRUKE/04/015). Radiother Oncol. 2011 Jul;100(1):93-100. doi: 10.1016/j.radonc.2011.06.026.

  PMID: 21752481 RESULT

• Murray Brunt A, Haviland JS, Wheatley DA, Sydenham MA, Alhasso A, Bloomfield DJ, Chan C, Churn M, Cleator S, Coles CE, Goodman A, Harnett A, Hopwood P, Kirby AM, Kirwan CC, Morris C, Nabi Z, Sawyer E, Somaiah N, Stones L, Syndikus I, Bliss JM, Yarnold JR; FAST-Forward Trial Management Group. Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial. Lancet. 2020 May 23;395(10237):1613-1626. doi: 10.1016/S0140-6736(20)30932-6. Epub 2020 Apr 28.

  PMID: 32580883 RESULT

• Lewis P, Brunt AM, Coles C, Griffin S, Locke I, Roques T; Breast Radiotherapy Consensus Working Group. Moving Forward Fast with FAST-Forward. Clin Oncol (R Coll Radiol). 2021 Jul;33(7):427-429. doi: 10.1016/j.clon.2021.04.007. Epub 2021 May 14. No abstract available.

  PMID: 33994270 RESULT

• Montero A, Ciervide R, Canadillas C, Alvarez B, Garcia-Aranda M, Alonso R, Lopez M, Chen-Zhao X, Alonso L, Valero J, Sanchez E, Hernando O, Garcia de Acilu P, Fernandez-Leton P, Rubio C. Acute skin toxicity of ultra-hypofractionated whole breast radiotherapy with simultaneous integrated boost for early breast cancer. Clin Transl Radiat Oncol. 2023 Jun 15;41:100651. doi: 10.1016/j.ctro.2023.100651. eCollection 2023 Jul.

  PMID: 37388711 RESULT

• Monten C, Lievens Y, Olteanu LAM, Paelinck L, Speleers B, Deseyne P, Van Den Broecke R, De Neve W, Veldeman L. Highly Accelerated Irradiation in 5 Fractions (HAI-5): Feasibility in Elderly Women With Early or Locally Advanced Breast Cancer. Int J Radiat Oncol Biol Phys. 2017 Jul 15;98(4):922-930. doi: 10.1016/j.ijrobp.2017.01.229. Epub 2017 Feb 1.

  PMID: 28366576 RESULT

• Van Hulle H, Vakaet V, Monten C, Deseyne P, Schoepen M, Colman C, Paelinck L, Van Greveling A, Post G, Speleers B, Vandecasteele K, Mareel M, De Neve W, Veldeman L. Acute toxicity and health-related quality of life after accelerated whole breast irradiation in 5 fractions with simultaneous integrated boost. Breast. 2021 Feb;55:105-111. doi: 10.1016/j.breast.2020.12.009. Epub 2020 Dec 24.

  PMID: 33401157 RESULT

• Boccardi M, Cilla S, Fanelli M, Romano C, Bonome P, Ferro M, Pezzulla D, Di Marco R, Deodato F, Macchia G. Ultra-Hypofractionated Whole Breast Radiotherapy with Automated Hybrid-VMAT Technique: A Pilot Study on Safety, Skin Toxicity and Aesthetic Outcomes. Breast Cancer (Dove Med Press). 2024 Sep 16;16:611-619. doi: 10.2147/BCTT.S470417. eCollection 2024.

  PMID: 39310783 RESULT

• Coles CE, Aristei C, Bliss J, Boersma L, Brunt AM, Chatterjee S, Hanna G, Jagsi R, Kaidar Person O, Kirby A, Mjaaland I, Meattini I, Luis AM, Marta GN, Offersen B, Poortmans P, Rivera S. International Guidelines on Radiation Therapy for Breast Cancer During the COVID-19 Pandemic. Clin Oncol (R Coll Radiol). 2020 May;32(5):279-281. doi: 10.1016/j.clon.2020.03.006. No abstract available.

  PMID: 32241520 RESULT

• Meattini I, Palumbo I, Becherini C, Borghesi S, Cucciarelli F, Dicuonzo S, Fiorentino A, Spoto R, Poortmans P, Aristei C, Livi L. The Italian Association for Radiotherapy and Clinical Oncology (AIRO) position statements for postoperative breast cancer radiation therapy volume, dose, and fractionation. Radiol Med. 2022 Dec;127(12):1407-1411. doi: 10.1007/s11547-022-01563-9. Epub 2022 Oct 6.

  PMID: 36201098 RESULT

• Brunt AM, Haviland JS, Wheatley DA, Sydenham MA, Bloomfield DJ, Chan C, Cleator S, Coles CE, Donovan E, Fleming H, Glynn D, Goodman A, Griffin S, Hopwood P, Kirby AM, Kirwan CC, Nabi Z, Patel J, Sawyer E, Somaiah N, Syndikus I, Venables K, Yarnold JR, Bliss JM; FAST-Forward Trial Management Group. One versus three weeks hypofractionated whole breast radiotherapy for early breast cancer treatment: the FAST-Forward phase III RCT. Health Technol Assess. 2023 Nov;27(25):1-176. doi: 10.3310/WWBF1044.

  PMID: 37991196 RESULT

• Chatterjee S, Chakraborty S; HYPORT Adjuvant Author Group. Hypofractionated radiation therapy comparing a standard radiotherapy schedule (over 3 weeks) with a novel 1-week schedule in adjuvant breast cancer: an open-label randomized controlled study (HYPORT-Adjuvant)-study protocol for a multicentre, randomized phase III trial. Trials. 2020 Sep 30;21(1):819. doi: 10.1186/s13063-020-04751-y.

  PMID: 32998747 RESULT

• Chakraborty S, Chatterjee S; Hyport Adjuvant Author Group. HYPORT adjuvant acute toxicity and patient dosimetry quality assurance results - Interim analysis. Radiother Oncol. 2022 Sep;174:59-68. doi: 10.1016/j.radonc.2022.07.003. Epub 2022 Jul 9.

  PMID: 35817323 RESULT

• Ratosa I, Montero A, Ciervide R, Alvarez B, Garcia-Aranda M, Valero J, Chen-Zhao X, Lopez M, Zucca D, Hernando O, Sanchez E, de la Casa MA, Alonso R, Fernandez-Leton P, Rubio C. Ultra-hypofractionated one-week locoregional radiotherapy for patients with early breast cancer: Acute toxicity results. Clin Transl Radiat Oncol. 2024 Mar 13;46:100764. doi: 10.1016/j.ctro.2024.100764. eCollection 2024 May.

  PMID: 38516338 RESULT

• Yadav BS, Dey T. Hypofractionation for Regional Nodal Irradiation in Breast Cancer: Best of Both the Worlds. Clin Breast Cancer. 2024 Jul;24(5):399-410. doi: 10.1016/j.clbc.2024.03.007. Epub 2024 Mar 14.

  PMID: 38614852 RESULT

• Boyages J, Harris JR. Local therapy of invasive disease. Hematol Oncol Clin North Am. 1989 Dec;3(4):675-90.

  PMID: 2691494 RESULT

• Mannino M, Yarnold J. Accelerated partial breast irradiation trials: diversity in rationale and design. Radiother Oncol. 2009 Apr;91(1):16-22. doi: 10.1016/j.radonc.2008.12.011. Epub 2009 Jan 27.

  PMID: 19178972 RESULT

• Holland R, Connolly JL, Gelman R, Mravunac M, Hendriks JH, Verbeek AL, Schnitt SJ, Silver B, Boyages J, Harris JR. The presence of an extensive intraductal component following a limited excision correlates with prominent residual disease in the remainder of the breast. J Clin Oncol. 1990 Jan;8(1):113-8. doi: 10.1200/JCO.1990.8.1.113.

  PMID: 2153190 RESULT

• Romestaing P, Lehingue Y, Carrie C, Coquard R, Montbarbon X, Ardiet JM, Mamelle N, Gerard JP. Role of a 10-Gy boost in the conservative treatment of early breast cancer: results of a randomized clinical trial in Lyon, France. J Clin Oncol. 1997 Mar;15(3):963-8. doi: 10.1200/JCO.1997.15.3.963.

  PMID: 9060534 RESULT

• Bartelink H, Horiot JC, Poortmans PM, Struikmans H, Van den Bogaert W, Fourquet A, Jager JJ, Hoogenraad WJ, Oei SB, Warlam-Rodenhuis CC, Pierart M, Collette L. Impact of a higher radiation dose on local control and survival in breast-conserving therapy of early breast cancer: 10-year results of the randomized boost versus no boost EORTC 22881-10882 trial. J Clin Oncol. 2007 Aug 1;25(22):3259-65. doi: 10.1200/JCO.2007.11.4991. Epub 2007 Jun 18.

  PMID: 17577015 RESULT

• Bartelink H, Maingon P, Poortmans P, Weltens C, Fourquet A, Jager J, Schinagl D, Oei B, Rodenhuis C, Horiot JC, Struikmans H, Van Limbergen E, Kirova Y, Elkhuizen P, Bongartz R, Miralbell R, Morgan D, Dubois JB, Remouchamps V, Mirimanoff RO, Collette S, Collette L; European Organisation for Research and Treatment of Cancer Radiation Oncology and Breast Cancer Groups. Whole-breast irradiation with or without a boost for patients treated with breast-conserving surgery for early breast cancer: 20-year follow-up of a randomised phase 3 trial. Lancet Oncol. 2015 Jan;16(1):47-56. doi: 10.1016/S1470-2045(14)71156-8. Epub 2014 Dec 9.

  PMID: 25500422 RESULT

• Fodor A, Brombin C, Mangili P, Borroni F, Pasetti M, Tummineri R, Zerbetto F, Longobardi B, Perna L, Dell'Oca I, Deantoni CL, Deli AM, Chiara A, Broggi S, Castriconi R, Esposito PG, Slim N, Passoni P, Baroni S, Villa SL, Rancoita PMV, Fiorino C, Del Vecchio A, Bianchini G, Gentilini OD, Di Serio MS, Di Muzio NG. Impact of molecular subtype on 1325 early-stage breast cancer patients homogeneously treated with hypofractionated radiotherapy without boost: Should the indications for radiotherapy be more personalized? Breast. 2021 Feb;55:45-54. doi: 10.1016/j.breast.2020.12.004. Epub 2020 Dec 9.

  PMID: 33326894 RESULT

• Whelan TJ, Kim DH, Sussman J. Clinical experience using hypofractionated radiation schedules in breast cancer. Semin Radiat Oncol. 2008 Oct;18(4):257-64. doi: 10.1016/j.semradonc.2008.04.008.

  PMID: 18725113 RESULT

• Qi XS, White J, Li XA. Is alpha/beta for breast cancer really low? Radiother Oncol. 2011 Aug;100(2):282-8. doi: 10.1016/j.radonc.2011.01.010. Epub 2011 Feb 28.

  PMID: 21367477 RESULT

• Ray KJ, Sibson NR, Kiltie AE. Treatment of Breast and Prostate Cancer by Hypofractionated Radiotherapy: Potential Risks and Benefits. Clin Oncol (R Coll Radiol). 2015 Jul;27(7):420-6. doi: 10.1016/j.clon.2015.02.008. Epub 2015 Mar 7.

  PMID: 25752244 RESULT

• Brand DH, Kirby AM, Yarnold JR, Somaiah N. How Low Can You Go? The Radiobiology of Hypofractionation. Clin Oncol (R Coll Radiol). 2022 May;34(5):280-287. doi: 10.1016/j.clon.2022.02.009. Epub 2022 Mar 5.

  PMID: 35260319 RESULT

• van Leeuwen CM, Oei AL, Crezee J, Bel A, Franken NAP, Stalpers LJA, Kok HP. The alfa and beta of tumours: a review of parameters of the linear-quadratic model, derived from clinical radiotherapy studies. Radiat Oncol. 2018 May 16;13(1):96. doi: 10.1186/s13014-018-1040-z.

  PMID: 29769103 RESULT

• Schneider U, Besserer J, Mack A. Hypofractionated radiotherapy has the potential for second cancer reduction. Theor Biol Med Model. 2010 Feb 11;7:4. doi: 10.1186/1742-4682-7-4.

  PMID: 20149259 RESULT

• Dasu A, Toma-Dasu I, Olofsson J, Karlsson M. The use of risk estimation models for the induction of secondary cancers following radiotherapy. Acta Oncol. 2005;44(4):339-47. doi: 10.1080/02841860510029833.

  PMID: 16120542 RESULT

• Berrington de Gonzalez A, Gilbert E, Curtis R, Inskip P, Kleinerman R, Morton L, Rajaraman P, Little MP. Second solid cancers after radiation therapy: a systematic review of the epidemiologic studies of the radiation dose-response relationship. Int J Radiat Oncol Biol Phys. 2013 Jun 1;86(2):224-33. doi: 10.1016/j.ijrobp.2012.09.001. Epub 2012 Oct 24.

  PMID: 23102695 RESULT

• Sitathanee C, Tangboonduangjit P, Dhanachai M, Suntiwong S, Yongvithisatid P, Rutchantuk S, Changkaew P, Watjiranon R, Khachonkham S, Boonkitticharoen V. Secondary cancer risk from modern external-beam radiotherapy of prostate cancer patients: Impact of fractionation and dose distribution. J Radiat Res. 2021 Jul 10;62(4):707-717. doi: 10.1093/jrr/rrab038.

  PMID: 33993271 RESULT

• Ciabattoni A, Gregucci F, De Rose F, Falivene S, Fozza A, Daidone A, Morra A, Smaniotto D, Barbara R, Lozza L, Vidali C, Borghesi S, Palumbo I, Huscher A, Perrucci E, Baldissera A, Tolento G, Rovea P, Franco P, De Santis MC, Grazia AD, Marino L, Meduri B, Cucciarelli F, Aristei C, Bertoni F, Guenzi M, Leonardi MC, Livi L, Nardone L, De Felice F, Rosetto ME, Mazzuoli L, Anselmo P, Arcidiacono F, Barbarino R, Martinetti M, Pasinetti N, Desideri I, Marazzi F, Ivaldi G, Bonzano E, Cavallari M, Cerreta V, Fusco V, Sarno L, Bonanni A, Mangiacotti MG, Prisco A, Buonfrate G, Andrulli D, Fontana A, Bagnoli R, Marinelli L, Reverberi C, Scalabrino G, Corazzi F, Doino D, Di Genesio-Pagliuca M, Lazzari M, Mascioni F, Pace MP, Mazza M, Vitucci P, Spera A, Macchia G, Boccardi M, Evangelista G, Sola B, La Porta MR, Fiorentino A, Levra NG, Ippolito E, Silipigni S, Osti MF, Mignogna M, Alessandro M, Ursini LA, Nuzzo M, Meattini I, D'Ermo G. AIRO Breast Cancer Group Best Clinical Practice 2022 Update. Tumori. 2022 Jul;108(2_suppl):1-144. doi: 10.1177/03008916221088885.

  PMID: 36112842 RESULT

• Offersen BV, Boersma LJ, Kirkove C, Hol S, Aznar MC, Biete Sola A, Kirova YM, Pignol JP, Remouchamps V, Verhoeven K, Weltens C, Arenas M, Gabrys D, Kopek N, Krause M, Lundstedt D, Marinko T, Montero A, Yarnold J, Poortmans P. ESTRO consensus guideline on target volume delineation for elective radiation therapy of early stage breast cancer. Radiother Oncol. 2015 Jan;114(1):3-10. doi: 10.1016/j.radonc.2014.11.030. Epub 2015 Jan 24.

  PMID: 25630428 RESULT

• Duane F, Aznar MC, Bartlett F, Cutter DJ, Darby SC, Jagsi R, Lorenzen EL, McArdle O, McGale P, Myerson S, Rahimi K, Vivekanandan S, Warren S, Taylor CW. A cardiac contouring atlas for radiotherapy. Radiother Oncol. 2017 Mar;122(3):416-422. doi: 10.1016/j.radonc.2017.01.008. Epub 2017 Feb 21.

  PMID: 28233564 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Andrei Fodor, MD

  IRCCS San Raffaele Scientific Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrei Fodor, MD

CONTACT

+390226437634; fodor.andrei@hsr.it

Roberta Tummineri, MD

CONTACT

+390226435452; tummineri.roberta@hsr.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: A total of 458 patients are expected to be enrolled in this prospective, randomized study. A power of 80% and a significance level α of 5% are used to calculate the sample size. The hypothesis is that the proportion of patients free from local recurrence 5 years after the end of treatment is not less than 95.4%, with a margin of 5%. A total of 218 patients per arm are needed, and an additional 5% (22 patients) to compensate for dropouts.

Study Record Dates

• First Submitted: May 27, 2025
• First Posted: June 13, 2025
• Study Start: July 25, 2025
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2035
• Last Updated: July 28, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: for 5 years after the end of the study
• Access Criteria: request from the corresponding author approved by the Lombardy Territorial Ethics Committee

Locations

IT (1)