Clinical trial NCT07020780: 5 fr Ultrahypofractionated WBI and SIB for Breast Cancer With Unfavorable Characteristics
Official title: Five Fractions Ultrahypofractionated Whole Breast Radiotherapy and Simultaneous Integrated Boost to the Tumor Bed, for Breast Cancer Patients With Unfavorable Characteristics
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Breast Cancer
Keywords: Breast Cancer
Whole Breast Irradiation
Simultaneous Integrated Boost
Adjuvant Radiotherapy
Utrahypofractionated Radiotherapy
Moderately Hypofractionated Radiotherapy
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
First posted: 2025-06-13
Enrollment: 458
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Detailed description: The project refers to a study on patients with T1-T3 Nx-N3 breast cancer, aged under 40 years or with unfavorable histology (lobular carcinoma, multifocal tumor, or histological subtypes Luminal B Her2 positive, Hormonal Receptors negative Her 2 positive, Triple Negative Breast Cancer-TNBC-) treated with breast-conserving surgery (BCS) and radiotherapy to the whole breast (+/- lymph node areas) to a total dose of 26 Gy in 5 fractions, with simultaneous boost (SIB) to the tumor bed to the total dose of 30 Gy, that will be compared with the current departmental standard of moderately hypofractionated radiotherapy to the whole breast, to 40.05 Gy in 15 fractions, with SIB to the tumor bed to a total dose of 48 Gy.

Eligibility criteria: Inclusion Criteria:

1. Histological diagnosis of breast cancer
2. 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)
3. Signed informed consent
4. Clinical stage T1-T3, Nx-N3
5. Negative surgical margins (≥ 0.2 cm)
6. Clinical M0 in the previous 3 months
7. PS (ECOG) ≤2
8. No previous thoracic radiotherapy
9. Fertile women using contraceptive methods started during oncological treatment

Exclusion Criteria:

1. Patients with favorable characteristics (Luminal A, Luminal B Her2 negative, ≥ 40 years) undergoing partial irradiation
2. Patients who have undergone mastectomy
3. Multicentric tumors
4. Positive or close surgical margins (\<0.2 cm)
5. BRCA1/2 positive (only if known)
6. Serious systemic diseases
7. Mental or other disorders that may prevent the patient from signing the informed consent
8. 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)
9. Collagen or autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, scleroderma, Sjogren's syndrome)
10. Evidence of distant metastases (M1)
11. Contraindication to treatment systemic
12. Pregnant women
13. Non-compliance with the dose limits established in the treatment plan

Primary outcomes:
measure: Local Relapse Free Survival (LRFS)
timeFrame: 5 years
Secondary outcomes:
measure: Acute toxicity
timeFrame: 1 month
measure: Acute toxicity
timeFrame: 3 months
measure: Late toxicity
timeFrame: 5 years
measure: Late toxicity
timeFrame: 5 years
measure: Local Control
timeFrame: 5 years
measure: Ipsilateral Breast Tumor Recurrence (IBTR)
timeFrame: 5 years
measure: Regional Relapse-Free Survival (RRFS)
timeFrame: From the date of radiotherapy end until the date of regional relapse, assessed up to 5 years
measure: Distant Metastasis-Free Survival (DMFS)
timeFrame: From the date of radiotherapy end until the date of distant metasis diagnosis, assessed up to 5 years
measure: Disease-Free Survival (DFS)
timeFrame: From the date of radiotherapy end until the date of first, any ( local, regional, distant) relapse, assessed up to 5 years
measure: Breast Cancer Specific Survival (BCSS)
timeFrame: From the date of radiotherapy end until the date of death from breast cancer, assessed up to 5 years
measure: Overall Survival (OS)
timeFrame: From the date of radiotherapy end until the date of death from any cause, assessed up to 5 years
measure: Cosmesis
timeFrame: 5 years
measure: Acute toxicity interim analysis
timeFrame: 3 months
measure: Late toxicity interim analysis
timeFrame: 42 months
measure: Local relapse interim analysis
timeFrame: 42 months
measure: Incidence of Treatment-Emergent Adverse Events as assessed with breast tumor specific quality of life questionnaires
timeFrame: 5 years
measure: Modeling of organ movement
timeFrame: 15 days
measure: Radiomics
timeFrame: 5 years
measure: Predictive factors for toxicity
timeFrame: 5 years
measure: Predictive factors for disease progression
timeFrame: 5 years
measure: Predictive factors for death
timeFrame: 5 years
Other outcomes:
Locations:
city: Milan
country: Italy
facility: IRCCS San Raffaele Scientific Institute
Study officials:
affiliation: IRCCS San Raffaele Scientific Institute
name: Andrei Fodor, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Lievens Y. Hypofractionated breast radiotherapy: financial and economic consequences. Breast. 2010 Jun;19(3):192-7. doi: 10.1016/j.breast.2010.03.003.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Boyages J, Harris JR. Local therapy of invasive disease. Hematol Oncol Clin North Am. 1989 Dec;3(4):675-90.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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. Erratum In: Lancet Oncol. 2015 Jan;16(1):e6.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.