OPTimizing Irradiation Through Molecular Assessment of Lymph Node (OPTIMAL)

NCT02335957 | Completed DMC

• 1 other identifier: GIC-RAD-2014-02
• Study Type: interventional
• Target: 489
• Locations: 3 countries
• Sites: 50

Brief Summary

The main purpose of this study is to show the non-inferiority of the incidental irradiation, as compared to intentional irradiation of the axillary nodes, in terms of 5-years disease-free survival (DFS) of early stage breast cancer patients with limited affectation of sentinel node assessed by OSNA (250 to 15,000 copies/uL), treated with breast-conservative surgery without axillary lymphadenectomy.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Disease Free Survival

  The primary outcome will be the 5-years DFS. DFS is defined as the time from randomization to any breast cancer-related event, including local, regional or distant recurrence, or death from breast cancer.

  5 years

Secondary Outcomes (5)

• Time to loco-regional recurrence up 5-years

  5 years

• Time to distant recurrence up 5-years

  5 years

• Number of patients with acute toxicity, defined as any adverse event appearing up to one month after finalization of radiotherapy.

  7 years

• Number of patients with chronic toxicity, defined as any adverse event appearing during follow-up, up to 5 years.

  7 years

• Total irradiation dose (Gy) received in axillary levels I, II and III, supraclavicular fossa, and internal mammary chain volumes, at the end of radiotherapy.

  2 years

Study Arms (2)

Intentional irradiation of lymph nodes

OTHER

Patients will receive a total dose of 50 Gy in the whole breast and nodal areas(axillary I, II, III, and supraclavicular) with optimization of the technique, in daily fractions of 2 Gy and 5 fractions/week during 5 weeks.

Radiation: Irradiation

Incidental irradiation of lymph nodes

EXPERIMENTAL

Patients will receive a total dose of 50 Gy in the whole breast, but not aimed at nodal areas, with optimization of the technique, in daily fractions of 2 Gy and 5 fractions/week during 5 weeks.

Radiation: Irradiation

Interventions

Irradiation RADIATION

Intentional versus incidental irradiation of lymphatic node areas, administered using a lineal accelerator, after 3D delimitation of the supraclavicular and axillary levels I, II and III. In both treatment arms, further tumoral bed boost will be allowed according to the investigator criteria, whether dose contribution to the nodal areas can be calculated. Due to its nature, interventions cannot be asked.

Incidental irradiation of lymph nodes; Intentional irradiation of lymph nodes

Eligibility Criteria

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

You may qualify if:

• Infiltrating, ductal carcinoma of the breast.
• Treated with conservative surgery (tumorectomy or quadrantectomy) without lymphadenectomy.
• Sentinel lymph node assessed by OSNA, with TTL in the range 250 - 15,000 copies/μL.
• Age ≥ 18 yrs old.
• Karnofsky Index ≥ 70 %.
• Signed Informed Consent.

You may not qualify if:

• Other types of breast cancer different from infiltrating ductal carcinoma.
• Bilateral breast cancer.
• Males.
• Mastectomy or axillary homolateral lymph node dissection.
• Previous thoracic irradiation therapy.
• Systemic neoadjuvant therapy previous to surgery.
• Contraindications of radiotherapy (pregnancy, severe collagen diseases).
• Other neoplasms.
• Severe associated comorbidities that, according to the investigator criteria, may interfere with the study evaluations.

Sponsors & Collaborators

• Grupo de Investigación Clínica en Oncología Radioterapia: lead

Study Sites (50)

Hospital de Perugia

Perugia, Italy

Location

Hospital Espírito Santo

Evora, Portugal

Location

Centro Hospitalar De São João

Porto, Portugal

Location

Hospital Distrital de Santarém

Santarém, Portugal

Location

Hospital de Cruces

Barakaldo, Bilbao, Spain

Location

Hospital Universitario de Gran Canaria Dr. Negrín

Las Palmas de Gran Canaria, Canary Islands, Spain

Location

Complejo Hospitalario Universitario de Fuenlabrada

Fuenlabrada, Madrid, Spain

Location

Hospital Universitario Puerta de Hierro

Majadahonda, Madrid, Spain

Location

Hospital General Universitario de Santa Lucía

Cartagena, Murcia, Spain

Location

Complejo Hospitalario de Navarra

Pamplona, Navarre, Spain

Location

Fundación Hospital de Jove

Gijón, Principality of Asturias, Spain

Location

Centro Onoclógico de Galicia

A Coruña, Spain

Location

Complejo Hospitalario Universitario de Albacete

Albacete, Spain

Location

Hospital Universitario de la Ribera

Alzira, Spain

Location

Hospital Universitario Infanta Cristina

Badajoz, Spain

Location

Centro Médico Teknon

Barcelona, Spain

Location

Clínica Platon

Barcelona, Spain

Location

Hospital Clínic de Barcelona

Barcelona, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

ICO Duran i Reynals

Barcelona, Spain

Location

Hospital Universitario de Burgos

Burgos, Spain

Location

Hospital Universitario Puerta del Mar

Cadiz, Spain

Location

Hospital Provincial de Castellón

Castelló, Spain

Location

Hospital General Universitario de Ciudad Real

Ciudad Real, Spain

Location

Hospital de Donostia

Donostia / San Sebastian, Spain

Location

Hospital Universitario Virgen de las Nieves

Granada, Spain

Location

Hospital Universitario de León

León, Spain

Location

Hospital Universitari Arnau de Vilanova

Lleida, Spain

Location

Hospital Clínico Universitario de San Carlos

Madrid, Spain

Location

Hospital Fundación Jiménez Díaz

Madrid, Spain

Location

Hospital Ramon y Cajal

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario Gregorio Marañón

Madrid, Spain

Location

Hospital Universitario la Paz

Madrid, Spain

Location

Hospital General Universitario Virgen de la Arrixaca

Murcia, Spain

Location

Hospital Universitari Sant Joan de Reus

Reus, Spain

Location

Hospital Universitario de Salamanca

Salamanca, Spain

Location

Hospital Clínico Universitario de Santiago

Santiago de Compostela, Spain

Location

Hospital Virgen de la Macarena

Seville, Spain

Location

Hospital Virgen del Rocío

Seville, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, Spain

Location

Hospital General Universitario de Valencia

Valencia, Spain

Location

Hospital Universitari i Politecnic la Fe

Valencia, Spain

Location

Instituto Valenciano de Oncología (IVO)

Valencia, Spain

Location

Hospital Clínico Universitario de Valladolid

Valladolid, Spain

Location

Complejo Hospitalario Universitario de Vigo

Vigo, Spain

Location

Hospital Universitario de Araba

Vitoria-Gasteiz, Spain

Location

Hospital Virgen de la Concha

Zamora, Spain

Location

Hospital Clínico Universitario Lozano Blesa

Zaragoza, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, Spain

Location

Related Publications (21)

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• Early Breast Cancer Trialists' Collaborative Group (EBCTCG); Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, Cutter D, Davies C, Ewertz M, Godwin J, Gray R, Pierce L, Whelan T, Wang Y, Peto R. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011 Nov 12;378(9804):1707-16. doi: 10.1016/S0140-6736(11)61629-2. Epub 2011 Oct 19.

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• Ragaz J, Olivotto IA, Spinelli JJ, Phillips N, Jackson SM, Wilson KS, Knowling MA, Coppin CM, Weir L, Gelmon K, Le N, Durand R, Coldman AJ, Manji M. Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. J Natl Cancer Inst. 2005 Jan 19;97(2):116-26. doi: 10.1093/jnci/djh297.

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• Overgaard M, Nielsen HM, Overgaard J. Is the benefit of postmastectomy irradiation limited to patients with four or more positive nodes, as recommended in international consensus reports? A subgroup analysis of the DBCG 82 b&c randomized trials. Radiother Oncol. 2007 Mar;82(3):247-53. doi: 10.1016/j.radonc.2007.02.001. Epub 2007 Feb 15.

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• van Wely BJ, Teerenstra S, Schinagl DA, Aufenacker TJ, de Wilt JH, Strobbe LJ. Systematic review of the effect of external beam radiation therapy to the breast on axillary recurrence after negative sentinel lymph node biopsy. Br J Surg. 2011 Mar;98(3):326-33. doi: 10.1002/bjs.7360. Epub 2010 Nov 30.

  PMID: 21254004 BACKGROUND

• Peg V, Espinosa-Bravo M, Vieites B, Vilardell F, Antunez JR, de Salas MS, Delgado-Sanchez JJ, Pinto W, Gozalbo F, Petit A, Sansano I, Del Mar Tellez M, Rubio IT. Intraoperative molecular analysis of total tumor load in sentinel lymph node: a new predictor of axillary status in early breast cancer patients. Breast Cancer Res Treat. 2013 May;139(1):87-93. doi: 10.1007/s10549-013-2524-z. Epub 2013 Apr 11.

  PMID: 23576079 BACKGROUND

• Veronesi U, Orecchia R, Zurrida S, Galimberti V, Luini A, Veronesi P, Gatti G, D'Aiuto G, Cataliotti L, Paolucci R, Piccolo P, Massaioli N, Sismondi P, Rulli A, Lo Sardo F, Recalcati A, Terribile D, Acerbi A, Rotmensz N, Maisonneuve P. Avoiding axillary dissection in breast cancer surgery: a randomized trial to assess the role of axillary radiotherapy. Ann Oncol. 2005 Mar;16(3):383-8. doi: 10.1093/annonc/mdi089. Epub 2005 Jan 24.

  PMID: 15668261 BACKGROUND

• Martelli G, Boracchi P, De Palo M, Pilotti S, Oriana S, Zucali R, Daidone MG, De Palo G. A randomized trial comparing axillary dissection to no axillary dissection in older patients with T1N0 breast cancer: results after 5 years of follow-up. Ann Surg. 2005 Jul;242(1):1-6; discussion 7-9. doi: 10.1097/01.sla.0000167759.15670.14.

  PMID: 15973094 BACKGROUND

• Hwang RF, Gonzalez-Angulo AM, Yi M, Buchholz TA, Meric-Bernstam F, Kuerer HM, Babiera GV, Tereffe W, Liu DD, Hunt KK. Low locoregional failure rates in selected breast cancer patients with tumor-positive sentinel lymph nodes who do not undergo completion axillary dissection. Cancer. 2007 Aug 15;110(4):723-30. doi: 10.1002/cncr.22847.

  PMID: 17587208 BACKGROUND

• Bilimoria KY, Bentrem DJ, Hansen NM, Bethke KP, Rademaker AW, Ko CY, Winchester DP, Winchester DJ. Comparison of sentinel lymph node biopsy alone and completion axillary lymph node dissection for node-positive breast cancer. J Clin Oncol. 2009 Jun 20;27(18):2946-53. doi: 10.1200/JCO.2008.19.5750. Epub 2009 Apr 13.

  PMID: 19364968 BACKGROUND

• Veronesi U, Viale G, Paganelli G, Zurrida S, Luini A, Galimberti V, Veronesi P, Intra M, Maisonneuve P, Zucca F, Gatti G, Mazzarol G, De Cicco C, Vezzoli D. Sentinel lymph node biopsy in breast cancer: ten-year results of a randomized controlled study. Ann Surg. 2010 Apr;251(4):595-600. doi: 10.1097/SLA.0b013e3181c0e92a.

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• Caudle AS, Hunt KK, Kuerer HM, Meric-Bernstam F, Lucci A, Bedrosian I, Babiera GV, Hwang RF, Ross MI, Feig BW, Hoffman K, Litton JK, Sahin AA, Yang W, Hortobagyi GN, Buchholz TA, Mittendorf EA. Multidisciplinary considerations in the implementation of the findings from the American College of Surgeons Oncology Group (ACOSOG) Z0011 study: a practice-changing trial. Ann Surg Oncol. 2011 Sep;18(9):2407-12. doi: 10.1245/s10434-011-1593-7. No abstract available.

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• Giuliano AE, McCall L, Beitsch P, Whitworth PW, Blumencranz P, Leitch AM, Saha S, Hunt KK, Morrow M, Ballman K. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons Oncology Group Z0011 randomized trial. Ann Surg. 2010 Sep;252(3):426-32; discussion 432-3. doi: 10.1097/SLA.0b013e3181f08f32.

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• Giuliano AE, Hunt KK, Ballman KV, Beitsch PD, Whitworth PW, Blumencranz PW, Leitch AM, Saha S, McCall LM, Morrow M. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. 2011 Feb 9;305(6):569-75. doi: 10.1001/jama.2011.90.

  PMID: 21304082 BACKGROUND

• Carlson RW, Hudis CA, Pritchard KI; National Comprehensive Cancer Network Breast Cancer Clinical Practice Guidelines in Oncology; American Society of Clinical Oncology Technology Assessment on the Use of Aromatase Inhibitors; St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer. Adjuvant endocrine therapy in hormone receptor-positive postmenopausal breast cancer: evolution of NCCN, ASCO, and St Gallen recommendations. J Natl Compr Canc Netw. 2006 Nov;4(10):971-9. doi: 10.6004/jnccn.2006.0082.

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• Haffty BG, Hunt KK, Harris JR, Buchholz TA. Positive sentinel nodes without axillary dissection: implications for the radiation oncologist. J Clin Oncol. 2011 Dec 1;29(34):4479-81. doi: 10.1200/JCO.2011.36.1667. Epub 2011 Oct 31. No abstract available.

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• Bayo E, Herruzo I, Arenas M, Algara M. Consensus on the regional lymph nodes irradiation in breast cancer. Clin Transl Oncol. 2013 Oct;15(10):766-73. doi: 10.1007/s12094-013-1027-z. Epub 2013 Mar 22.

  PMID: 23519538 BACKGROUND

• Algara M, Rodriguez E, Martinez-Arcelus FJ, Salinas J, Sanz X, Beato I, Manso A, Soler A, Rodriguez JR, Frias A, Calin A, Juan G, Meireles P, Flaquer A; OPTIMAL investigators. OPTimizing Irradiation through Molecular Assessment of Lymph node (OPTIMAL): a randomized clinical trial. Radiother Oncol. 2022 Nov;176:76-82. doi: 10.1016/j.radonc.2022.09.006. Epub 2022 Sep 19.

  PMID: 36210628 DERIVED

• Algara Lopez M, Rodriguez Garcia E, Beato Tortajada I, Martinez Arcelus FJ, Salinas Ramos J, Rodriguez Garrido JR, Sanz Latiesas X, Soler Rodriguez A, Juan Rijo G, Flaquer Garcia A. OPTimizing Irradiation through Molecular Assessment of Lymph node (OPTIMAL): a randomized open label trial. Radiat Oncol. 2020 Oct 2;15(1):229. doi: 10.1186/s13014-020-01672-7.

  PMID: 33008422 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Radiation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Physical Phenomena

Study Officials

• Manuel Algara López, Medicine

  Grupo de Investigación Clínica en Oncología Radioterápica (GICOR)

  PRINCIPAL INVESTIGATOR

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: ST

Study Record Dates

• First Submitted: December 23, 2014
• First Posted: January 12, 2015
• Study Start: April 1, 2015
• Primary Completion: July 1, 2021
• Study Completion: July 1, 2021
• Last Updated: April 1, 2022

Record last verified: 2022-03

Locations

IT (1); PT (3); ES (46)