Axillary Reverse Mapping (ARM) in Breast Cancer Surgery to Prevent Lymphedema. (ARMtrial)

NCT03333226 | Unknown

• 1 other identifier: RF-2013-02358165
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Breast cancer related lymphedema (BCRL) is a debilitating and distressing condition affecting approximately one out of five breast cancer survivors. BCRL is a chronic swelling of the upper arm following axillary lymph nodes dissection, and it is associated to a significant functional, psychological and social morbidity, with an heavy impact on life quality. Several studies reported BCRL incidence between 6.7% and 62.5% for different population cohorts. Randomized clinical trials (RCTs) reported that sentinel lymph node biopsy (SLNB) when compared with axillary lymph node dissection (ALND) leads to a significant reduction in postoperative complications. However, the advent of SLNB does not solve the problem of BCRL with a concrete chance to develop a lymphedema after single SLNB around 7%. Health care cost of BCRL rehabilitative treatment is not available in literature yet. Few studies considered incidence, risk factors and treatment costs of BCRL among working-age women after breast cancer treatment, reporting that BCRL population had significantly higher rehabilitative medical costs ($14,877 to $23,167) with twice as much risk to develop BCRL complications, such as lymphangitis or cellulitis when compared to "BCRL free" population (OR = 2.02, P = .009). Axillary reverse mapping (ARM) procedure claims to map and preserve arm lymphatic drainage during ALND and/or during SLNB, reducing BCRL development. ARM is developed as result of assumption that arm's lymphatic pathway is not involved by metastatic tumor cells of the primary breast cancer. However, when the arm lymph node correspond to the SLN it should be removed for correct tumor staging, thus a lymphatic drainage disruption onset will be expected with BCRL risk increase. During the ARM procedure, a fluorescence imaging technique (photodynamic procedure) is useful for detecting lymphatic drainage of the upper limb and it allows in differentiating the fluorescent ARM node from the SLN identified by the radioguided technique (99mTC-Nanocoll).

Conditions

Breast Cancer Lymphedema

Keywords

Breast Neoplasms; Sentinel Lymph Node Biopsy; Lymph Node Excision; Technetium Tc 99m; Indocyanine Green; Lymphatic System; Secondary Prevention

Outcome Measures

Primary Outcomes (1)

• Incidence of Breast Cancer Related Lymphedema (BCRL) after Axillary Lymph Node Dissection (ALND)

  Incidence of BCRL in patients in whom the ARM lymph node is preserved compared to those in which it is removed. Clinically follow-up will include the clinical presentation (pain, integumentary abnormalities, paresthesia, hypoesthesia, neuro-vascular deficits), standardized measurement of 7 records \[diameters of the upper limb (hand, wrist, 15 cm and 10 cm distally to olecranon, elbow (olecranon), 10 cm and 15 cm proximally to olecranon)\] and final conversion into volumes.

  From the day of surgery to 12 months after surgery

Secondary Outcomes (3)

• Incidence of Breast Cancer Related Lymphedema (BCRL) after Sentinel Lymph Node Biopsy (SLNB) alone

  From the day of surgery to 12 months after surgery

• Crossover between Sentinel Lymph Node (SLN) of the Breast and the ARM lymph node

  Intraoperatively

• Lymphoscintigraphic sub-clinical modifications of arm lymphatic drainage after ALND

  The day before ALND and at 60 days after ALND

Study Arms (2)

ARM lymph node preservation

EXPERIMENTAL

All patients will be sent to both rSLNB and photodynamic Axillary Reverse Mapping (ARM) to evaluate the crossover between SLN and ARM lymph node. In case of SLN metastases, an ALND with ARM lymph node preservation will be performed.

Procedure: Axillary Reverse Mapping (ARM)

ARM lymph node removal

ACTIVE COMPARATOR

All patients will be sent to both rSLNB and photodynamic Axillary Reverse Mapping (ARM) to evaluate the crossover between SLN and ARM lymph node. In case of SLN metastases, an ALND with ARM lymph node removal will be performed.

Procedure: Axillary Reverse Mapping (ARM)

Interventions

Axillary Reverse Mapping (ARM) PROCEDURE

ARM lymph node preservation versus removal

ARM lymph node preservation; ARM lymph node removal

Eligibility Criteria

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

You may qualify if:

• T1-T2 stage breast cancer

You may not qualify if:

• axillary lymph node metastasis;
• previous surgery on the ipsilateral axilla;
• neoadjuvant chemo-radiotherapy;
• presence of primitive lymphedema of the arm;
• allergy to Iodine, thyroid disease, renal and hepatic impairment (for issues related to Indocyanine Green)
• pregnancy;
• patients refusing to participate in the study.

Sponsors & Collaborators

• University Hospital of Ferrara: lead

Study Sites (1)

Azienda Ospedaliero Universitaria S. Anna

Cona, Ferrara, 44124, Italy

RECRUITING

Related Publications (12)

• Sakorafas GH, Peros G, Cataliotti L, Vlastos G. Lymphedema following axillary lymph node dissection for breast cancer. Surg Oncol. 2006 Nov;15(3):153-65. doi: 10.1016/j.suronc.2006.11.003. Epub 2006 Dec 21.

  PMID: 17187979 BACKGROUND

• McWayne J, Heiney SP. Psychologic and social sequelae of secondary lymphedema: a review. Cancer. 2005 Aug 1;104(3):457-66. doi: 10.1002/cncr.21195.

  PMID: 15968692 BACKGROUND

• Purushotham AD, Upponi S, Klevesath MB, Bobrow L, Millar K, Myles JP, Duffy SW. Morbidity after sentinel lymph node biopsy in primary breast cancer: results from a randomized controlled trial. J Clin Oncol. 2005 Jul 1;23(19):4312-21. doi: 10.1200/JCO.2005.03.228.

  PMID: 15994144 BACKGROUND

• Wilke LG, McCall LM, Posther KE, Whitworth PW, Reintgen DS, Leitch AM, Gabram SG, Lucci A, Cox CE, Hunt KK, Herndon JE 2nd, Giuliano AE. Surgical complications associated with sentinel lymph node biopsy: results from a prospective international cooperative group trial. Ann Surg Oncol. 2006 Apr;13(4):491-500. doi: 10.1245/ASO.2006.05.013. Epub 2006 Mar 2.

  PMID: 16514477 BACKGROUND

• Shih YC, Xu Y, Cormier JN, Giordano S, Ridner SH, Buchholz TA, Perkins GH, Elting LS. Incidence, treatment costs, and complications of lymphedema after breast cancer among women of working age: a 2-year follow-up study. J Clin Oncol. 2009 Apr 20;27(12):2007-14. doi: 10.1200/JCO.2008.18.3517. Epub 2009 Mar 16.

  PMID: 19289624 BACKGROUND

• Ponzone R, Mininanni P, Cassina E, Sismondi P. Axillary reverse mapping in breast cancer: can we spare what we find? Ann Surg Oncol. 2008 Jan;15(1):390-1; author reply 392-3. doi: 10.1245/s10434-007-9663-6. Epub 2007 Nov 8. No abstract available.

  PMID: 17990039 BACKGROUND

• Boneti C, Korourian S, Diaz Z, Santiago C, Mumford S, Adkins L, Klimberg VS. Scientific Impact Award: Axillary reverse mapping (ARM) to identify and protect lymphatics draining the arm during axillary lymphadenectomy. Am J Surg. 2009 Oct;198(4):482-7. doi: 10.1016/j.amjsurg.2009.06.008.

  PMID: 19800452 BACKGROUND

• Britton TB, Solanki CK, Pinder SE, Mortimer PS, Peters AM, Purushotham AD. Lymphatic drainage pathways of the breast and the upper limb. Nucl Med Commun. 2009 Jun;30(6):427-30. doi: 10.1097/MNM.0b013e328315a6c6.

  PMID: 19319006 BACKGROUND

• Noguchi M, Noguchi M, Nakano Y, Ohno Y, Kosaka T. Axillary reverse mapping using a fluorescence imaging system in breast cancer. J Surg Oncol. 2012 Mar;105(3):229-34. doi: 10.1002/jso.22094. Epub 2011 Sep 12.

  PMID: 21913193 BACKGROUND

• Han C, Yang B, Zuo WS, Zheng G, Yang L, Zheng MZ. The Feasibility and Oncological Safety of Axillary Reverse Mapping in Patients with Breast Cancer: A Systematic Review and Meta-Analysis of Prospective Studies. PLoS One. 2016 Feb 26;11(2):e0150285. doi: 10.1371/journal.pone.0150285. eCollection 2016.

  PMID: 26919589 BACKGROUND

• Yue T, Zhuang D, Zhou P, Zheng L, Fan Z, Zhu J, Hou L, Yu F, Dong X, Xiao L, He Q. A Prospective Study to Assess the Feasibility of Axillary Reverse Mapping and Evaluate Its Effect on Preventing Lymphedema in Breast Cancer Patients. Clin Breast Cancer. 2015 Aug;15(4):301-6. doi: 10.1016/j.clbc.2015.01.010. Epub 2015 Feb 19.

  PMID: 25776198 BACKGROUND

• Sarri AJ, Dias R, Laurienzo CE, Goncalves MC, Dias DS, Moriguchi SM. Arm lymphoscintigraphy after axillary lymph node dissection or sentinel lymph node biopsy in breast cancer. Onco Targets Ther. 2017 Mar 6;10:1451-1457. doi: 10.2147/OTT.S117830. eCollection 2017.

  PMID: 28331338 BACKGROUND

MeSH Terms

Conditions

Breast Cancer Lymphedema; Breast Neoplasms

Condition Hierarchy (Ancestors)

Lymphedema; Lymphatic Diseases; Hemic and Lymphatic Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Paolo Carcoforo, MD

CONTACT

0039 0532 236123; paolo.carcoforo@unife.it

Mattia Portinari, MD

CONTACT

0039 0532 236100; mattia.portinari@unife.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Patients will be randomized before the SLNB procedure. Due to the type of intervention, the blinding of the treating surgeon will not be possible, thus the surgeon will be aware of both the intraoperative crossover between ARM lymph node and SLN (secondary outcome) and the allocation to ARM lymph node preservation or removal. Data about BCRL (primary outcome) will be collected by the physiatrist and the physiotherapist that will be blinded about the allocation (ARM lymph node preservation/removal) and the crossover between SLN of the breast and the arm's lymph node. The assessment of lymphoscintigraphic subclinical modification in the arm lymphatic drainage after SLNB and ALND (secondary outcomes) will be performed by a blinded nuclear medicine physician that will not be aware of the allocation (ARM lymph node preservation/removal) and the crossover between ARM lymph node and breast's SLN.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: Eligible patients for radioguided sentinel lymph node biopsy (rSLNB) will be randomly divided in two groups: 1. experimental group in which all patients will be sent to both rSLNB and photodynamic Axillary Reverse Mapping (ARM) to evaluate the crossover between SLN and ARM lymph node. In case of SLN metastases, an ALND with ARM lymph node preservation will be performed. 2. control group in which all patients will be sent to both rSLNB and photodynamic Axillary Reverse Mapping (ARM) to evaluate the crossover between SLN and ARM lymph node. In case of SLN metastases, an ALND with ARM lymph node removal will be performed.

Study Record Dates

• First Submitted: November 2, 2017
• First Posted: November 6, 2017
• Study Start: January 17, 2018
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: January 23, 2018

Record last verified: 2018-01

Locations

IT (1)