Intra-Operative Electron Boost and Hypofractionated Whole-Breast Irradiation During Breast-conserving Treatment (BCT)

NCT01343459 | Completed DMC

• 2 other identifiers: ISIORT - 01ISIORT 01
• Study Type: interventional
• Target: 1,464
• Locations: 1 country
• Sites: 1

Brief Summary

Title: HIOB - Hypofractionated Whole-Breast Irradiation preceded by Intraoperative Radiotherapy with Electrons as anticipated Boost ISIORT- 01 HIOB is defined as hypofractionated WBRT (40,5 Gy in 2,7 Gy per fraction) preceded by an Intraoperative Boost to the tumor bed ( 90 % reference dose of 10 Gy, 11,1 Gy Dmax IOERT). Primary endpoint is the proof of superiority of a new treatment regimen. The HIOB study concept is supposed to test the hypothesis whether such a combined schedule is superior (or iso-effective) towards "standard" RT in terms of local control and cosmetic outcome. In the vast majority of all publications, annual and 5 year in-breast recurrence rates following BCT showed a clear dependency on patient age within the following boundaries (primary references): Age \> 50: Bartelink (standard): 0,7% (annual) 3,5% (5y) START B (best): 0,4 %(annual) 2,0% (5y) Age 41-50: Bartelink (standard) 1,2% (annual) 6,0% (5y) Whelan (best) 0,72%(annual) 3,6% (5y) Age ≥ 35-40 Bartelink (standard) 2% (annual) 10% (5y) Whelan (best) 0,72% (annual) 3,6% (5y) long these three different age groups, benchmarking will be performed against the best published results following 'Golden Standard'RT, usually defined as conventionally fractionated WBRT with 50 Gy (25 x2) plus external tumor bed boost with 10-16 Gy electrons (5-8x2Gy). Superiority is defined as going below the lower limit of the estimated 5 year local recurrence rate within the respective age group Inferiority is defined as crossing the respective upper limit . Secondary endpoint: Disease free survival Tertiary endpoint: toxicity assessment (acute and late) including long term cosmetic evaluation Study design and statistics:

• Prospective multicenter single-armed
• Sequential probability ratio test (SPRT)
• Separate analysis within three different age groups Estimated Accrual time: strongly dependent on recruitment per year within the respective age group . Due to the statistical estimation of Szenario A and B the study will close after max. Time-period of 10 years in case of A or 6,4 years in case of B.. Principal investigators and study coordinators: UC of Radiotherapy and Radio-Oncology UC of Special Gynecology and Breast Cancer Center Landeskrankenhaus Salzburg, Paracelsus University Clinics

Conditions

Local Neoplasm Recurrence; Toxicity

Keywords

Hypofractionated Whole breast irradiation; Hypofractionated Whole breast irradiation long term results; Breast conserving therapy; IORT with electrons in breast cancer; IOERT as anticipated Boost; IOERT and hypofractionated whole breast irradiation

Outcome Measures

Primary Outcomes (1)

• 5 year local recurrence rate: Sequential Probability Ratio Test

  Sequential Probability Ratio Test

  10 years

Secondary Outcomes (1)

• Acute toxicity: CTC-toxicity Scoring-system;Late toxicity: LENT-SOMA scoring-systems

  10 years

Other Outcomes (1)

• Cosmesis

  10 years

Study Arms (1)

IOERT followed by hypofractionated WBRT

EXPERIMENTAL

HIOB: IOERT of 11.1 Gy followed by WBRT with 15 times 2.7 Gy per fraction.

Radiation: HIOB

Interventions

HIOB RADIATION

IOERT single shot as a boost followed by hypofractionated WBRT (HIOB) * IOERT is performed on mobile or fixed linacs * Reference dose: 11 Gy specified as maximum dose, with a minimum target volume dose of 90% encompassing the PTV (i.e. 10 Gy). WBRT * must start within day 36- 56 postoperatively (week 6 - 8 p.o.) in case of adjuvant hormonal treatment (or no further tumor specific medication) * In case of adjuvant chemotherapy, a time - gap between IOERT and WBRT up to 9 months is allowed. * Single reference dose per fraction: 2,7 Gy (ICRU) * Number of fractions: 15, Number of fractions per week: 5 * Total WBRT dose: 40,5 Gy

IOERT followed by hypofractionated WBRT

Eligibility Criteria

• Age: 35 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological proven invasive breast carcinoma
• Age: ≥ 35 years
• Tumor stage T1-2
• nodal status: N0-1
• Freedom of surgical margins: R0 (both invasive and in situ component), that means no ink on tumors (invasive or in situ) (ago-online.de) .
• Also multifocal disease within the same quadrant with a maximum distance of \< 5 cm
• all grades G1-G3
• Hormonal receptor and Her-2 status: no limitations
• Informed and undersigned consent

You may not qualify if:

• In-situ Carcinoma without invasive component
• Age \< 35
• Tumor stage T3,4
• Nodal status \>N1
• if irradiation of regional lymphatics is required
• Re-excision after IOERT
• Immediately secondary mastectomy (not due to recurrence).
• Multicentricity according to international definition: \> 5 cm distance to each other
• previous radiotherapy to the involved breast
• Karnofsky Index \< 70%
• Mixed connective tissue diseases including rheumatoid Polyarthritis, Thrombangitis obliterans
• Chronic pre-existent lung disease (Lung fibrosis, Pneumokoniosis, late-type Allergies like Farmer lung; Asthma bronchiale, severe Emphysema, COPD III \*)
• Cardiac Co-Morbidity: clinically positive coronary vessel disease, St.p. myocardial infarction, pacemakers and/or defibrillators)
• Distant metastases
• breast size (PTV) \> 2500 ml

Sponsors & Collaborators

• Paracelsus Medical University: lead
• LKH Klagenfurt: collaborator
• Poznan University of Medical Sciences: collaborator
• San Filippo Neri General Hospital: collaborator
• Avera McKennan Hospital & University Health Center: collaborator
• St. Luke's Hospital ,Cedar Rapids, US: collaborator
• A.O.U. San Giovanni Battista di Torino, Italy: collaborator
• IRCCS Cancer Referral Center of Basilicata: collaborator
• Heinrich-Heine University, Duesseldorf: collaborator
• St. Elisabeth-Hospital Köln-Hohenlind, Germany: collaborator
• S.C. Radiotherapia Aziendale Umbria, Italy: collaborator
• Azienda Ospedaliero, Universitaria Ospedali Riuniti: collaborator
• Fondazione Salvatore Maugeri: collaborator
• Marien Hospital Düsseldorf: collaborator
• Azienda Ospedaliero Universitaria Maggiore della Carita: collaborator
• Philipps University Marburg: collaborator
• Istituti Tumori Giovanni Paolo II: collaborator
• University Hospital of Ferrara: collaborator

Study Sites (1)

Paracelsus private university; University Clinic of Radio-Oncology

Salzburg, 5020, Austria

Location

Related Publications (12)

• Bartelink H, Horiot JC, Poortmans P, Struikmans H, Van den Bogaert W, Barillot I, Fourquet A, Borger J, Jager J, Hoogenraad W, Collette L, Pierart M; European Organization for Research and Treatment of Cancer Radiotherapy and Breast Cancer Groups. Recurrence rates after treatment of breast cancer with standard radiotherapy with or without additional radiation. N Engl J Med. 2001 Nov 8;345(19):1378-87. doi: 10.1056/NEJMoa010874.

  PMID: 11794170 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Ivaldi GB, Leonardi MC, Orecchia R, Zerini D, Morra A, Galimberti V, Gatti G, Luini A, Veronesi P, Ciocca M, Sangalli C, Fodor C, Veronesi U. Preliminary results of electron intraoperative therapy boost and hypofractionated external beam radiotherapy after breast-conserving surgery in premenopausal women. Int J Radiat Oncol Biol Phys. 2008 Oct 1;72(2):485-93. doi: 10.1016/j.ijrobp.2007.12.038. Epub 2008 Apr 11.

  PMID: 18407434 BACKGROUND

• START Trialists' Group; Bentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett-Lee PJ, 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 A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet Oncol. 2008 Apr;9(4):331-41. doi: 10.1016/S1470-2045(08)70077-9. Epub 2008 Mar 19.

  PMID: 18356109 BACKGROUND

• Owen JR, Ashton A, Bliss JM, Homewood J, Harper C, Hanson J, Haviland J, Bentzen SM, Yarnold JR. Effect of radiotherapy fraction size on tumour control in patients with early-stage breast cancer after local tumour excision: long-term results of a randomised trial. Lancet Oncol. 2006 Jun;7(6):467-71. doi: 10.1016/S1470-2045(06)70699-4.

  PMID: 16750496 BACKGROUND

• Yarnold J, Ashton A, Bliss J, Homewood J, Harper C, Hanson J, Haviland J, Bentzen S, Owen R. Fractionation sensitivity and dose response of late adverse effects in the breast after radiotherapy for early breast cancer: long-term results of a randomised trial. Radiother Oncol. 2005 Apr;75(1):9-17. doi: 10.1016/j.radonc.2005.01.005. Epub 2005 Mar 16.

  PMID: 15878095 BACKGROUND

• Reitsamer R, Sedlmayer F, Kopp M, Kametriser G, Menzel C, Deutschmann H, Nairz O, Hitzl W, Peintinger F. The Salzburg concept of intraoperative radiotherapy for breast cancer: results and considerations. Int J Cancer. 2006 Jun 1;118(11):2882-7. doi: 10.1002/ijc.21727.

  PMID: 16381011 BACKGROUND

• Reitsamer R, Peintinger F, Sedlmayer F, Kopp M, Menzel C, Cimpoca W, Glueck S, Rahim H, Kopp P, Deutschmann H, Merz F, Brandis M, Kogelnik H. Intraoperative radiotherapy given as a boost after breast-conserving surgery in breast cancer patients. Eur J Cancer. 2002 Aug;38(12):1607-10. doi: 10.1016/s0959-8049(02)00116-8.

  PMID: 12142049 BACKGROUND

• Sedlmayer F, Fastner G, Merz F, Deutschmann H, Reitsamer R, Menzel C, Ciabattoni A, Petrucci A, Hager E, Willich N, Orecchia R, Valentini V; International Society of Intraoperative Radiotherapy. IORT with electrons as boost strategy during breast conserving therapy in limited stage breast cancer: results of an ISIORT pooled analysis. Strahlenther Onkol. 2007 Dec;183 Spec No 2:32-4. doi: 10.1007/s00066-007-2013-6. No abstract available.

  PMID: 18167006 BACKGROUND

• Whelan T, MacKenzie R, Julian J, Levine M, Shelley W, Grimard L, Lada B, Lukka H, Perera F, Fyles A, Laukkanen E, Gulavita S, Benk V, Szechtman B. Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node-negative breast cancer. J Natl Cancer Inst. 2002 Aug 7;94(15):1143-50. doi: 10.1093/jnci/94.15.1143.

  PMID: 12165639 BACKGROUND

MeSH Terms

Conditions

Neoplasm Recurrence, Local

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Gerd Fastner, Assoc.Prof.

  Dep. of Radiotherapy and Radio-Oncology, Paracelsus Medical University Salzburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc. Prof., MD

Study Record Dates

• First Submitted: April 26, 2011
• First Posted: April 28, 2011
• Study Start: January 1, 2011
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: January 4, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)