Proton Therapy for Lymph Nodes in Breast Cancer

Breast Cancer Clinical Trial

— BR01  

Official title:

Proton Therapy for Peripheral Lymph Nodes in Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01365845
• Other study ID #: IRB201701740
• Secondary ID: UFPTI 1016-BR01
• Status: Completed
• Phase: N/A
• Start date: April 2012
• Est. completion date: May 23, 2018

Study information

• Verified date: May 2018
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if proton radiation therapy will reduce the amount of heart that is exposed to radiation, thereby decreasing the frequency and/or severity of any cardiac side effects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: May 23, 2018
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• Pathologically confirmed invasive adenocarcinoma of the breast stage I-III (TX, T0-4, N0-3) with medially located tumor and/or axillary node invasion.

• Patients must have undergone either mastectomy or breast conservation surgery.

• Patients are required to have axillary staging which can include sentinel node biopsy alone if sentinel node is negative.

• Patient must require peripheral lymph node radiation per physician discretion.

Exclusion Criteria:

• Evidence of distant metastasis (M1).

• Prior radiotherapy to the area of interest.

• Prior history of cardiovascular disease per physician discretion.

• Prior or concurrent cancer other than non-melanomatous skin cancer unless disease free for at least 5 years.

• Collagen vascular disease, specifically dermatomyositis with a CPK level above normal or with an active skin rash, systemic lupus erythematosis or scleroderma.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Radiation:
• Photon
50.4 Gy to the breast/chest wall and peripheral lymph nodes at 1.8 Gy per fraction
• 3D-Proton/Conventional plan or 3D-proton only
50.4 Cobalt Gray Equivalent/Gray to the breast/chest wall and peripheral lymph nodes at 1.8 Cobalt Gray Equivalent/Gray per fraction

Locations

Country	Name	City	State
United States	University of Florida Proton Therapy Institute	Jacksonville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of Florida

Country where clinical trial is conducted

United States, 

References & Publications (22)

Arriagada R, Lê MG, Mouriesse H, Fontaine F, Dewar J, Rochard F, Spielmann M, Lacour J, Tubiana M, Sarrazin D. Long-term effect of internal mammary chain treatment. Results of a multivariate analysis of 1195 patients with operable breast cancer and positive axillary nodes. Radiother Oncol. 1988 Mar;11(3):213-22. — View Citation

Avisar E, Molina MA, Scarlata M, Moffat FL. Internal mammary sentinel node biopsy for breast cancer. Am J Surg. 2008 Oct;196(4):490-4. doi: 10.1016/j.amjsurg.2008.06.003. Epub 2008 Aug 23. — View Citation

Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans V, Godwin J, Gray R, Hicks C, James S, MacKinnon E, McGale P, McHugh T, Peto R, Taylor C, Wang Y; Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005 Dec 17;366(9503):2087-106. Review. — View Citation

Cuzick J, Stewart H, Rutqvist L, Houghton J, Edwards R, Redmond C, Peto R, Baum M, Fisher B, Host H, et al. Cause-specific mortality in long-term survivors of breast cancer who participated in trials of radiotherapy. J Clin Oncol. 1994 Mar;12(3):447-53. — View Citation

Darby SC, McGale P, Taylor CW, Peto R. Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 300,000 women in US SEER cancer registries. Lancet Oncol. 2005 Aug;6(8):557-65. — View Citation

Farrús B, Vidal-Sicart S, Velasco M, Zanón G, Fernández PL, Muñoz M, Santamaría G, Albanell J, Biete A. Incidence of internal mammary node metastases after a sentinel lymph node technique in breast cancer and its implication in the radiotherapy plan. Int J Radiat Oncol Biol Phys. 2004 Nov 1;60(3):715-21. — View Citation

Freedman GM, Fowble BL, Nicolaou N, Sigurdson ER, Torosian MH, Boraas MC, Hoffman JP. Should internal mammary lymph nodes in breast cancer be a target for the radiation oncologist? Int J Radiat Oncol Biol Phys. 2000 Mar 1;46(4):805-14. Review. — View Citation

Heuts EM, van der Ent FW, von Meyenfeldt MF, Voogd AC. Internal mammary lymph drainage and sentinel node biopsy in breast cancer - A study on 1008 patients. Eur J Surg Oncol. 2009 Mar;35(3):252-7. doi: 10.1016/j.ejso.2008.06.1493. Epub 2008 Aug 5. — View Citation

Højris I, Overgaard M, Christensen JJ, Overgaard J. Morbidity and mortality of ischaemic heart disease in high-risk breast-cancer patients after adjuvant postmastectomy systemic treatment with or without radiotherapy: analysis of DBCG 82b and 82c randomised trials. Radiotherapy Committee of the Danish Breast Cancer Cooperative Group. Lancet. 1999 Oct 23;354(9188):1425-30. — View Citation

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96. doi: 10.3322/CA.2007.0010. Epub 2008 Feb 20. — View Citation

Kahán Z, Csenki M, Varga Z, Szil E, Cserháti A, Balogh A, Gyulai Z, Mándi Y, Boda K, Thurzó L. The risk of early and late lung sequelae after conformal radiotherapy in breast cancer patients. Int J Radiat Oncol Biol Phys. 2007 Jul 1;68(3):673-81. Epub 2007 Mar 9. — View Citation

Kwa SL, Lebesque JV, Theuws JC, Marks LB, Munley MT, Bentel G, Oetzel D, Spahn U, Graham MV, Drzymala RE, Purdy JA, Lichter AS, Martel MK, Ten Haken RK. Radiation pneumonitis as a function of mean lung dose: an analysis of pooled data of 540 patients. Int J Radiat Oncol Biol Phys. 1998 Aug 1;42(1):1-9. — View Citation

Lind PA, Marks LB, Hardenbergh PH, Clough R, Fan M, Hollis D, Hernando ML, Lucas D, Piepgrass A, Prosnitz LR. Technical factors associated with radiation pneumonitis after local +/- regional radiation therapy for breast cancer. Int J Radiat Oncol Biol Phys. 2002 Jan 1;52(1):137-43. — View Citation

Marks LB, Munley MT, Bentel GC, Zhou SM, Hollis D, Scarfone C, Sibley GS, Kong FM, Jirtle R, Jaszczak R, Coleman RE, Tapson V, Anscher M. Physical and biological predictors of changes in whole-lung function following thoracic irradiation. Int J Radiat Oncol Biol Phys. 1997 Oct 1;39(3):563-70. — View Citation

N. Xu, M. Ho, C.G. Morris, N.P. Mendenhall. Proton treatment of peripheral lymph nodes in breast cancer. Int J Radiat Oncol Biol Phys 2010; 78: S803.

Overgaard M, Hansen PS, Overgaard J, Rose C, Andersson M, Bach F, Kjaer M, Gadeberg CC, Mouridsen HT, Jensen MB, Zedeler K. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial. N Engl J Med. 1997 Oct 2;337(14):949-55. — View Citation

Overgaard M, Jensen MB, Overgaard J, Hansen PS, Rose C, Andersson M, Kamby C, Kjaer M, Gadeberg CC, Rasmussen BB, Blichert-Toft M, Mouridsen HT. Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet. 1999 May 15;353(9165):1641-8. — View Citation

Ragaz J, Jackson SM, Le N, Plenderleith IH, Spinelli JJ, Basco VE, Wilson KS, Knowling MA, Coppin CM, Paradis M, Coldman AJ, Olivotto IA. Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med. 1997 Oct 2;337(14):956-62. — View Citation

TURNER-WARWICK RT. The lymphatics of the breast. Br J Surg. 1959 May;46:574-82. — View Citation

Veronesi U, Arnone P, Veronesi P, Galimberti V, Luini A, Rotmensz N, Botteri E, Ivaldi GB, Leonardi MC, Viale G, Sagona A, Paganelli G, Panzeri R, Orecchia R. The value of radiotherapy on metastatic internal mammary nodes in breast cancer. Results on a large series. Ann Oncol. 2008 Sep;19(9):1553-60. doi: 10.1093/annonc/mdn183. Epub 2008 May 7. — View Citation

Veronesi U, Marubini E, Mariani L, Valagussa P, Zucali R. The dissection of internal mammary nodes does not improve the survival of breast cancer patients. 30-year results of a randomised trial. Eur J Cancer. 1999 Sep;35(9):1320-5. — View Citation

Wennberg B, Gagliardi G, Sundbom L, Svane G, Lind P. Early response of lung in breast cancer irradiation: radiologic density changes measured by CT and symptomatic radiation pneumonitis. Int J Radiat Oncol Biol Phys. 2002 Apr 1;52(5):1196-206. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Volume of Heart Receiving = 5 Gray (Gy)/Cobalt Gray Equivalent (CGE)	A reduction of 50% in heart volume exposed to radiation doses = 5 Gy/CGE was considered preferred outcome in this study plan.	2 weeks prior to starting radiation therapy.
Secondary	Secondary Dosimetric Endpoint	Assess improvements in other dosimetry endpoints including lung dose (mean lung dose, V20, V5), heart dose (mean heart, V20, V5), mean dose to the thyroid, mean esophageal dose, D95 coverage for axillary, supraclavicular and internal mammary nodes, maximal spinal cord dose (Dmax) and skin Dmax.	2 weeks prior to starting radiation therapy.
Secondary	Assessment of Acute Side Effects	Assess acute toxicities including pericarditis, pneumonitis, dermatitis, fatigue, and nausea.	Participants will be assessed weekly during radiation therapy for an expected average of 7 weeks.
Secondary	Assessment of Longterm Side Effects and Disease Specific End Points.	Assess late toxicities including clinical and sub-clinical heart disease, pulmonary fibrosis, soft tissue fibrosis, rib fracture, and secondary malignancies.; Analyze local control, progression-free survival, and overall survival.	1 month following completion of treatment, then every 6 months for 5 years, then annually thereafter.
Secondary	Assessment of Cardiac Function Markers	Assess levels of cardiac function markers Troponin and Brain Naturietic Peptide before and after treatment.	after treatment

External Links

•   University of Florida Proton Therapy Institute website