Randomized Trial on Intraoperative Radiotherapy Full Dose Vs External Radiotherapy

Carcinoma Breast Clinical Trial

— ELIOT  

Official title:

Randomized Clinical Trial: Comparison Between Quadrantectomy Followed by External Fractionated Radiotherapy and Quadrantectomy Associated With Intraoperative Radiotherapy in Women >= 48 Years of Age Affected by Early-stage Breast Carcinoma.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01849133
• Other study ID #: IEO S65/500
• Status: Completed
• Phase: N/A
• First received: May 5, 2013
• Last updated: May 5, 2013
• Start date: November 2000
• Est. completion date: December 2012

Study information

• Verified date: May 2013
• Source: European Institute of Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate the efficacy of exclusive intraoperative radiation therapy after conserving surgery in early-stage breast cancer compared with whole breast radiotherapy. The primary outcome was the rate of ipsilateral true recurrence ( any recurrence at or close to primary tumor bed) and new ipsilateral tumors ( any recurrence occurring in quadrants other than the previous one) and the recurrence free survival.

Description:

The ELIOT trial is a prospective single center randomised phase III trial which compared intraoperative radiotherapy with electrons to the tumor bed with conventional scheme of whole breast external beam radiotherapy. Patients were randomly allocated to intraoperative radiotherapy group or external radiotherapy group in a 1:1 ratio.

The rationale for providing partial breast irradiation to the tumor bed lies on the patterns of ipsilateral breast tumor relapse reported in Literature. In fact, the majority of recurrences occur close to the tumor bed. Several randomized trials of breast conserving surgery with or without whole breast radiotherapy showed that in 75-90% of cases recurrences were at the site of original primary tumor. In this context, limiting irradiation to the tumor bed may result in a similar local control as whole breast irradiation, provided that patients are properly selected.

The intraoperative treatment was delivered with a mobile miniaturized accelerator, located in the operating room, while for external radiotherapy a 6 MV linear accelerator was used. The surgical technique to perform ELIOT has been standardized in every step. The breast gland is prepared by separating it from the subcutaneous tissue and the underlying pectoralis muscle and by restoring the continuity of the surgical breach after having protected the thoracic wall by lead and aluminium disks to optimize the delivered dose. The linear accelerator delivers electrons at variable energy, ranging from 3 to 9 MeV: the proper electron energy is chosen according to the target thickness. Collimation is achieved by hard-docking system, consisting of 5 mm thick high- quality polymethyl methacrylate round applicators of 4 to 10 -cm diameter.

For radiation protection a primary beam stopper and mobile 1.5 cm thick lead shields are provided. The prescribed dose was 21 Gy at the 90% isodose. After delivery of the radiation dose, the applicator and the disk were removed and the gland is reconstructed again.

In the conventional arm of the study, the external beam radiotherapy is given after the full recovery from the surgical excision. All patients undergo virtual simulation including a treatment-planning CT scan. The clinical target volume is defined to extend to 5 mm below the skin surface and include breast parenchyma down to the deep fascia, but not including the underlying muscle and rib cage. The irradiated volume should extend medially to the midline, laterally to the mid axillary line and inferiorly to 1-2 cm below the level of intra-mammary fold and superiorly to the suprasternal notch. Using BEV, the blocks are used to shield as much heart and lung as possible without compromising the PTV.

Treatment is delivered by a pair of tangential fields with wedges as necessary. The prescribed dose to the whole-breast was 50 Gy delivered in 2 Gy fraction over 5 weeks with a 6 -megavolt linear accelerator followed by a sequential boost of 10 Gy to the tumor bed with electrons. A PTV dose homogeneity of -5% + 7% as recommended by ICRU (International Commission on Radiation Units and Measurements) report no 50.

Patients were followed up with at least 6-month clinical examination up to 5 years and then every 8 months thereafter. Annual mammogram was performed .

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1305
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 48 Years to 75 Years

Eligibility

Inclusion Criteria:

• Age = 48 and < 75

• Clinical mammographic/ultrasound diagnosis of unicentric carcinoma, with ultrasound diameter =2.5 cm. Advisable, but not mandatory, the execution of mammoscintigraphy with MDP-99mTc (Methyl diphosphonate technetium-99m) : this procedure allows the bone staging and the mapping of eventual multi-focality/multi-centricity of the breast neoplasm.

• No previous therapy (biopsy included) for breast cancer in other Institutions.

• Patients with non-palpable lesions will undergo preoperative centering and stereotactic and/or ultrasound-guided cytology (the execution of this last procedure is not mandatory).

• Adequate information to the patient and informed consent.

Exclusion Criteria:

• Ductal or lobular non-infiltrating carcinoma.

• Paget disease.

• Tumor in close proximity to the skin.

• Tumor in the axillary tail.

• Documented multi-centricity/multi-focality of the tumor.

• Patients who underwent excisional biopsy in other Institutions.

• Histology different from carcinoma.

• Personal anamnesis positive for malignancy (basocellular carcinoma, in situ carcinoma of the cervix, contralateral breast cancer free of disease after 15 years of follow-up excluded).

• General contraindications to regular follow-up or radiotherapy.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Carcinoma Breast

Intervention

Radiation:
• external fractionated radiotherapy
conventional external beam radiotherapy
• intraoperative radiotherapy
Intraoperative radiotherapy (IORT). Total delivered dose 21Gy (Gray), 90% isodose

Locations

Country	Name	City	State
Italy	European Institute of Oncology	Milan

Sponsors (1)

Lead Sponsor	Collaborator
European Institute of Oncology

Country where clinical trial is conducted

Italy, 

References & Publications (25)

Bernier J, Viale G, Orecchia R, Ballardini B, Richetti A, Bronz L, Franzetti-Pellanda A, Intra M, Veronesi U. Partial irradiation of the breast: Old challenges, new solutions. Breast. 2006 Aug;15(4):466-75. Epub 2006 Jan 24. — View Citation

Calvo FA, Meirino RM, Orecchia R. Intraoperative radiation therapy first part: rationale and techniques. Crit Rev Oncol Hematol. 2006 Aug;59(2):106-15. Epub 2006 Jul 14. Review. — View Citation

Calvo FA, Meirino RM, Orecchia R. intraoperative radiation therapy part 2. Clinical results. Crit Rev Oncol Hematol. 2006 Aug;59(2):116-27. Epub 2006 Jul 21. Review. — View Citation

Ciocca M, Orecchia R, Garibaldi C, Rondi E, Luini A, Gatti G, Intra M, Veronesi P, Lazzari R, Tosi G, Veronesi U. In vivo dosimetry using radiochromic films during intraoperative electron beam radiation therapy in early-stage breast cancer. Radiother Oncol. 2003 Dec;69(3):285-9. — View Citation

Ciocca M, Pedroli G, Orecchia R, Guido A, Cattani F, Cambria R, Veronesi U. Radiation survey around a Liac mobile electron linear accelerator for intraoperative radiation therapy. J Appl Clin Med Phys. 2009 Apr 28;10(2):2950. — View Citation

Ciocca M, Piazzi V, Lazzari R, Vavassori A, Luini A, Veronesi P, Galimberti V, Intra M, Guido A, Tosi G, Veronesi U, Orecchia R. Real-time in vivo dosimetry using micro-MOSFET detectors during intraoperative electron beam radiation therapy in early-stage breast cancer. Radiother Oncol. 2006 Feb;78(2):213-6. Epub 2005 Dec 15. — View Citation

Galimberti V, Ciocca M, Leonardi MC, Zanagnolo V, Paola B, Manuela S, Sahium RC, Lazzari R, Gentilini O, Peccatori F, Veronesi U, Orecchia R. Is electron beam intraoperative radiotherapy (ELIOT) safe in pregnant women with early breast cancer? In vivo dosimetry to assess fetal dose. Ann Surg Oncol. 2009 Jan;16(1):100-5. doi: 10.1245/s10434-008-0172-z. Epub 2008 Oct 21. — View Citation

Gatzemeier W, Orecchia R, Gatti G, Intra M, Veronesi U. [Intraoperative radiotherapy (IORT) in treatment of breast carcinoma--a new therapeutic alternative within the scope of breast-saving therapy? Current status and future prospects. Report of experiences from the European Institute of Oncology (EIO), Mailand]. Strahlenther Onkol. 2001 Jul;177(7):330-7. German. — View Citation

Intra M, Gatti G, Luini A, Galimberti V, Veronesi P, Zurrida S, Frasson A, Ciocca M, Orecchia R, Veronesi U. Surgical technique of intraoperative radiotherapy in conservative treatment of limited-stage breast cancer. Arch Surg. 2002 Jun;137(6):737-40. — View Citation

Intra M, Leonardi C, Luini A, Veronesi P, Gennari R, Gatti G, Ciocca M, Soteldo J, Bassi F, Venturino M, Orecchia R, Veronesi U. Full-dose intraoperative radiotherapy with electrons in breast surgery: broadening the indications. Arch Surg. 2005 Oct;140(10):936-9. — View Citation

Intra M, Leonardi MC, Gatti G, Vento AR, Ciocca M, Veronesi P, Bassani G, Dos Santos GR, Rodriguez J, Luini A, Orecchia R, Veronesi U. Intraoperative radiotherapy during breast conserving surgery in patients previously treated with radiotherapy for Hodgkin's disease. Tumori. 2004 Jan-Feb;90(1):13-6. — View Citation

Intra M, Luini A, Gatti G, Ciocca M, Gentilini OD, Viana AA, Chagas EM, Berrettini A, Schuh F, Scarpa D, Orecchia R, Veronesi U. Surgical technique of intraoperative radiation therapy with electrons (ELIOT) in breast cancer: a lesson learned by over 1000 — View Citation

Intra M, Orecchia R, Veronesi U. Intraoperative radiotherapy: the debate continues. Lancet Oncol. 2004 Jun;5(6):340. — View Citation

Luini A, Gatti G, Zurrida S, Talakhadze N, Brenelli F, Gilardi D, Paganelli G, Orecchia R, Cassano E, Viale G, Sangalli C, Ballardini B, dos Santos GR, Veronesi U. The evolution of the conservative approach to breast cancer. Breast. 2007 Apr;16(2):120-9. Review. — View Citation

Luini A, Orecchia R, Gatti G, Intra M, Ciocca M, Galimberti V, Veronesi P, Santos GR, Gilardi D, Veronesi U. The pilot trial on intraoperative radiotherapy with electrons (ELIOT): update on the results. Breast Cancer Res Treat. 2005 Sep;93(1):55-9. — View Citation

Orecchia R, Ciocca M, Lazzari R, Garibaldi C, Leonardi MC, Luini A, Intra M, Gatti G, Veronesi P, Petit JI, Veronesi U. Intraoperative radiation therapy with electrons (ELIOT) in early-stage breast cancer. Breast. 2003 Dec;12(6):483-90. — View Citation

Orecchia R, Ciocca M, Tosi G, Franzetti S, Luini A, Gatti G, Veronesi U. Intraoperative electron beam radiotherapy (ELIOT) to the breast: a need for a quality assurance programme. Breast. 2005 Dec;14(6):541-6. Epub 2005 Oct 19. — View Citation

Orecchia R, Ivaldi GB, Leonardi MC. Integrated breast conservation and intraoperative radiation therapy. Breast. 2009 Oct;18 Suppl 3:S98-102. doi: 10.1016/S0960-9776(09)70283-8. — View Citation

Orecchia R, Luini A, Veronesi P, Ciocca M, Franzetti S, Gatti G, Veronesi U. Electron intraoperative treatment in patients with early-stage breast cancer: data update. Expert Rev Anticancer Ther. 2006 Apr;6(4):605-11. Review. — View Citation

Petit JY, Veronesi U, Orecchia R, Luini A, Rey P, Intra M, Didier F, Martella S, Rietjens M, Garusi C, DeLorenzi F, Gatti G, Leon ME, Casadio C. Nipple-sparing mastectomy in association with intra operative radiotherapy (ELIOT): A new type of mastectomy for breast cancer treatment. Breast Cancer Res Treat. 2006 Mar;96(1):47-51. Epub 2005 Oct 27. — View Citation

Petit JY, Veronesi U, Orecchia R, Rey P, Martella S, Didier F, Viale G, Veronesi P, Luini A, Galimberti V, Bedolis R, Rietjens M, Garusi C, De Lorenzi F, Bosco R, Manconi A, Ivaldi GB, Youssef O. Nipple sparing mastectomy with nipple areola intraoperative radiotherapy: one thousand and one cases of a five years experience at the European institute of oncology of Milan (EIO). Breast Cancer Res Treat. 2009 Sep;117(2):333-8. doi: 10.1007/s10549-008-0304-y. Epub 2009 Jan 17. — View Citation

Rampinelli C, Bellomi M, Ivaldi GB, Intra M, Raimondi S, Meroni S, Orecchia R, Veronesi U. Assessment of pulmonary fibrosis after radiotherapy (RT) in breast conserving surgery: comparison between conventional external beam RT (EBRT) and intraoperative RT with electrons (ELIOT). Technol Cancer Res Treat. 2011 Aug;10(4):323-9. — View Citation

Veronesi U, Gatti G, Luini A, Intra M, Ciocca M, Sanchez D, Zurrida S, Navarro S, Orecchia R. Full-dose intraoperative radiotherapy with electrons during breast-conserving surgery. Arch Surg. 2003 Nov;138(11):1253-6. — View Citation

Veronesi U, Gatti G, Luini A, Intra M, Orecchia R, Borgen P, Zelefsky M, McCormick B, Sacchini V. Intraoperative radiation therapy for breast cancer: technical notes. Breast J. 2003 Mar-Apr;9(2):106-12. — View Citation

Veronesi U, Orecchia R, Luini A, Gatti G, Intra M, Zurrida S, Ivaldi G, Tosi G, Ciocca M, Tosoni A, De Lucia F. A preliminary report of intraoperative radiotherapy (IORT) in limited-stage breast cancers that are conservatively treated. Eur J Cancer. 2001 Nov;37(17):2178-83. — View Citation

* Note: There are 25 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of local relapses	local relapse of disease and ipsilateral second primary	5 YEARS	No