Breast Cancer LymphedemaNCT03333226
Axillary Reverse Mapping (ARM) in Breast Cancer Surgery to Prevent Lymphedema. (ARMtrial)
A study testing Axillary Reverse Mapping (ARM) in people with Breast Cancer Lymphedema, run by University Hospital of Ferrara at 1 site in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer Lymphedema
- What is being tested?
- Axillary Reverse Mapping (ARM)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteItaly
- Study dates
- 17 Jan 2018to Dec 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- T1-T2 stage breast cancer
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Azienda Ospedaliero Universitaria S. Anna
Cona, Ferrara, 44124
Paolo Carcoforo, MD, 0039 0532 236123, paolo.carcoforo@unife.it
Mattia Portinari, MD, 0039 0532 236100, mattia.portinari@unife.it
About this study
Official title: Axillary Reverse Mapping (ARM). Identification of the Arm Lymphatic Pathways in Breast Cancer Surgery to Prevent Breast Cancer Related Lymphedema (BCRL): a Randomized Clinical Trial.
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).
Read the detailed description
The investigators will conduct a randomized clinical trial (RCT) at the S. Anna University Hospital of Ferrara (Italy) on consecutive patients undergoing SLNB for breast cancer and subsequent ALND in case of SLN metastases. Eligible patients for radioguided sentinel lymph node biopsy (rSLNB) will be randomly divided in two groups: 1) experimental group in which patients undergoing rSLNB and ARM photodynamic procedure; and, in case of SLN metastases, subsequent ALND with ARM node preservation; 2) control group in which patients undergoing rSLNB and ARM photodynamic procedure; and, in case of SLN metastases, subsequent ALND with ARM node removal.
Consent procedure
Patients will be visited in the outpatient clinic by one of the treating surgeon, who will approach the subject and explain the study. If the patient is interested in participating, further details will be provided and consent will be obtained.
Experimental design
Step 1
Patients enrolled in both groups will be subjected to rSLNB associated to ARM photodynamic procedure.
Radioguided SLNB technique:
The day before surgery, four peri-areolar subcutaneous injections of Tc-99m Nanocoll® will be performed for an overall volume of 0.4 ml (standard activity of 74 MBq). Pre-operative imaging of SLN consists of an anterior and lateral static acquisition, generally performed between 1 and 5 hours post-injection (max. 18 hours), by means of a double head gammacamera (Siemens, ECAM). The gamma camera energy selection peak is centered on the 140 KeV of 99mTc (with a window of ± 10%), and the use of high-resolution collimators and of a 256x256 acquisition matrix. Acquisition time varies between 2 and 8 minutes. Cutaneous projection of SLN will be marked with a skin-marking pen. The day of surgery, after intraoperative routine prep and drape, a handheld gamma probe (EuroProbe III, EURORAD, Chennevières-sur-Marne, France) will be used to localize radioactivity before skin incision and during axillary dissection to identify SLN, that is defined by counts >10% of background.
ARM photodynamic procedure:
The day of surgery, 15 minutes before surgical incision, patients will be subjected to injection of 1 ml of ICG (5mg/ml) in the upper forearm and during SLNB we will perform an evaluation of lymphatic arm pathways with fluorescence (IC-Flow Diagnostic Green, SEDA S.p.a., Milano, Italy). If a crossover between SLN of the breast and the arm's lymph node will be find, the ARM lymph node identified by the photodynamic technique will be excised for pathological evaluation.
Step 2
Patients with tumor positive SLN, eligible for ALND, will undergo to preoperative arm lymphoscintigraphy in order to asses possible changes in lymphatic drainage pathways of the arm after rSLNB.
The day before ALND, an injection of a volume of 0.4 ml of Tc-99m Nanocoll® in each hand will be performed, fractioned in all interdigital space. The subsequent scintigraphic planar acquisition is performed using a double head gamma-camera (Siemens, Ecam) according the following protocol:
- 5 minutes post injection: imaging acquisition on hands and forearms positioned over collimator with a marker near right arm;
- 10 minutes post injection :anterior acquisition with gamma camera head 1 on elbows and shoulders;
- 15 minutes post injection : anterior acquisition on both axilla and thorax using cobalt wires markers drawing cranium profile;
- 20 minutes post injection :marking with skin-marking pen of skin projection of most radioactive axillary nodes;
- 120/180 minutes post injection : acquisition in the same position for checking of possible number and/or site changes of nodes marked before.
Step 3
Experimental group:
In case of SLN metastases, during radical ALND (I, II,III levels of Berg), the ARM lymph node identified with both radioguided and photodynamic methods will be isolated from the other axillary lymph nodes and preserved. Photodynamic method will also allow us to visualize the lymphatic drainage of the arm that will be preserved.
Control group:
In case of SLN metastases, during radical ALND (I, II,III levels of Berg), the ARM lymph node identified with both radioguided and photodynamic method will be isolated from the other axillary lymph nodes and removed.
Step 4
The post-operative follow up will be conducted in inpatient setting and after discharge in outpatient setting (surveillance for early and delayed surgical complications). All patients will be clinically evaluated at 10, 30, 60, and 180 days after surgery and undergoing bilateral arms lymphoscintigraphy at 60 days after surgery to determine possible lymphoscintigraphic changes underlying a subclinical BCRL. Clinically follow-up will include the clinical presentation (pain, integumentary abnormalities, paresthesia, hypoesthesia, neuro-vascular deficits), 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. In case of BCRL diagnosis patients will be addressed to rehabilitative center for therapy.
Statistical analysis
A prospective analysis will be obtained from database in which patients data will be collected, with details of the patients and tumors characteristics, lymphatic drainage of the upper extremity, intra- and post-operative outcome, and follow up. The power analysis, based on preliminary results, reports that 150 women in each group are required to achieve a power of 0.9 and to detect a significant difference (p<0.05). Data will be expressed as mean ± standard deviation or median (interquartile range - IQR 25-75) according to the distribution. The Shapiro-Wilk test will be used to assess the assumption of normality. Categorical data will be presented as number (%). Data will be analyzed using the Chi-square test to compare percentages, t-Student test will be used to compare the means and Mann-Whitney test to compare non parametric data. Logistic regression analysis will be employed to construct a model predicting BCRL using factors regarding the patient [age, gender, BMI, American Society of Anesthesiology (ASA) classification], the tumor (size, stage, bio-molecular characteristics ), crossover, type of intervention (preservation of ARM lymph node vs. dissection), and post-operative treatment (chemotherapy, radiotherapy). Significance will be considered for values of p<0.05. Statistical analysis will be performed with IBM SPSS Statistics for Windows, Version 24.0 (IBM Corp. Armonk, NY: IBM Corp.).
- Conditions
- Breast Cancer Lymphedema
- Being tested
- Axillary Reverse Mapping (ARM)
- Keywords
- Breast Neoplasms, Sentinel Lymph Node Biopsy, Lymph Node Excision, Technetium Tc 99m, Indocyanine Green, Lymphatic System, Secondary Prevention
- Medical subject headings
- Breast Cancer Lymphedema, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Axillary Reverse Mapping (ARM)Procedure or surgery
ARM lymph node preservation versus removal
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Procedure: Axillary Reverse Mapping (ARM) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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, the radioguided technique (Tc-99m Nanocoll) will be used to identify the SLN of the breast; at the same time, the Axillary Reverse Mapping (ARM) of the upper limb will be carried out by Indocyanine Green, and the ARM lymph node will be identified and preserved. If a crossover between SLN of the breast and the arm's lymph node will be find, the ARM lymph node identified by the photodynamic technique will be excised for pathological evaluation.
Measured: Intraoperatively
Lymphoscintigraphic sub-clinical modifications of arm lymphatic drainage after ALND
Bilateral arms lymphoscintigraphy
Measured: The day before ALND and at 60 days after ALND
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2017
- Study start17 Jan 2018
- Primary completionDec 2020 (estimated)
- Study completionDec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Breast Cancer LymphedemaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital of Ferrara
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Paolo Carcoforo, University Hospital of Ferrara
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03333226
- Sponsor's protocol ID
- RF-2013-02358165
- Status last verified
- Jan 2018
- First submitted
- 2 Nov 2017
- Last updated
- 23 Jan 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Formal requests will be evaluated.
Publications
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.
PubMed 17187979McWayne 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.
PubMed 15968692Purushotham 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.
PubMed 15994144Wilke 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.
PubMed 16514477Shih 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.
PubMed 19289624Ponzone 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.
PubMed 17990039Boneti 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.
PubMed 19800452Britton 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.
PubMed 19319006Noguchi 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.
PubMed 21913193Han 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.
PubMed 26919589Yue 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.
PubMed 25776198Sarri 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.
PubMed 28331338
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Axillary Reverse Mapping (ARM). Identification of the Arm Lymphatic Pathways in Breast Cancer Surgery to Prevent Breast Cancer Related Lymphedema (BCRL): a Randomized Clinical Trial.
- ClinicalTrials.gov ID
- NCT03333226
- Acronym / sponsor ID
- RF-2013-02358165
- Conditions
- Breast Cancer Lymphedema
- Keywords
- Breast Neoplasms, Sentinel Lymph Node Biopsy, Lymph Node Excision, Technetium Tc 99m, Indocyanine Green, Lymphatic System, Secondary Prevention
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- University Hospital of FerraraUniversity, hospital or other
- Study start
- 17 Jan 2018 (actual)
- Primary completion
- Dec 2020 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 6 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
The investigators will conduct a randomized clinical trial (RCT) at the S. Anna University Hospital of Ferrara (Italy) on consecutive patients undergoing SLNB for breast cancer and subsequent ALND in case of SLN metastases. Eligible patients for radioguided sentinel lymph node biopsy (rSLNB) will be randomly divided in two groups: 1) experimental group in which patients undergoing rSLNB and ARM photodynamic procedure; and, in case of SLN metastases, subsequent ALND with ARM node preservation; 2) control group in which patients undergoing rSLNB and ARM photodynamic procedure; and, in case of SLN metastases, subsequent ALND with ARM node removal.
Consent procedure
Patients will be visited in the outpatient clinic by one of the treating surgeon, who will approach the subject and explain the study. If the patient is interested in participating, further details will be provided and consent will be obtained.
Experimental design
Step 1
Patients enrolled in both groups will be subjected to rSLNB associated to ARM photodynamic procedure.
Radioguided SLNB technique:
The day before surgery, four peri-areolar subcutaneous injections of Tc-99m Nanocoll® will be performed for an overall volume of 0.4 ml (standard activity of 74 MBq). Pre-operative imaging of SLN consists of an anterior and lateral static acquisition, generally performed between 1 and 5 hours post-injection (max. 18 hours), by means of a double head gammacamera (Siemens, ECAM). The gamma camera energy selection peak is centered on the 140 KeV of 99mTc (with a window of ± 10%), and the use of high-resolution collimators and of a 256x256 acquisition matrix. Acquisition time varies between 2 and 8 minutes. Cutaneous projection of SLN will be marked with a skin-marking pen. The day of surgery, after intraoperative routine prep and drape, a handheld gamma probe (EuroProbe III, EURORAD, Chennevières-sur-Marne, France) will be used to localize radioactivity before skin incision and during axillary dissection to identify SLN, that is defined by counts >10% of background.
ARM photodynamic procedure:
The day of surgery, 15 minutes before surgical incision, patients will be subjected to injection of 1 ml of ICG (5mg/ml) in the upper forearm and during SLNB we will perform an evaluation of lymphatic arm pathways with fluorescence (IC-Flow Diagnostic Green, SEDA S.p.a., Milano, Italy). If a crossover between SLN of the breast and the arm's lymph node will be find, the ARM lymph node identified by the photodynamic technique will be excised for pathological evaluation.
Step 2
Patients with tumor positive SLN, eligible for ALND, will undergo to preoperative arm lymphoscintigraphy in order to asses possible changes in lymphatic drainage pathways of the arm after rSLNB.
The day before ALND, an injection of a volume of 0.4 ml of Tc-99m Nanocoll® in each hand will be performed, fractioned in all interdigital space. The subsequent scintigraphic planar acquisition is performed using a double head gamma-camera (Siemens, Ecam) according the following protocol:
- 5 minutes post injection: imaging acquisition on hands and forearms positioned over collimator with a marker near right arm;
- 10 minutes post injection :anterior acquisition with gamma camera head 1 on elbows and shoulders;
- 15 minutes post injection : anterior acquisition on both axilla and thorax using cobalt wires markers drawing cranium profile;
- 20 minutes post injection :marking with skin-marking pen of skin projection of most radioactive axillary nodes;
- 120/180 minutes post injection : acquisition in the same position for checking of possible number and/or site changes of nodes marked before.
Step 3
Experimental group:
In case of SLN metastases, during radical ALND (I, II,III levels of Berg), the ARM lymph node identified with both radioguided and photodynamic methods will be isolated from the other axillary lymph nodes and preserved. Photodynamic method will also allow us to visualize the lymphatic drainage of the arm that will be preserved.
Control group:
In case of SLN metastases, during radical ALND (I, II,III levels of Berg), the ARM lymph node identified with both radioguided and photodynamic method will be isolated from the other axillary lymph nodes and removed.
Step 4
The post-operative follow up will be conducted in inpatient setting and after discharge in outpatient setting (surveillance for early and delayed surgical complications). All patients will be clinically evaluated at 10, 30, 60, and 180 days after surgery and undergoing bilateral arms lymphoscintigraphy at 60 days after surgery to determine possible lymphoscintigraphic changes underlying a subclinical BCRL. Clinically follow-up will include the clinical presentation (pain, integumentary abnormalities, paresthesia, hypoesthesia, neuro-vascular deficits), 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. In case of BCRL diagnosis patients will be addressed to rehabilitative center for therapy.
Statistical analysis
A prospective analysis will be obtained from database in which patients data will be collected, with details of the patients and tumors characteristics, lymphatic drainage of the upper extremity, intra- and post-operative outcome, and follow up. The power analysis, based on preliminary results, reports that 150 women in each group are required to achieve a power of 0.9 and to detect a significant difference (p<0.05). Data will be expressed as mean ± standard deviation or median (interquartile range - IQR 25-75) according to the distribution. The Shapiro-Wilk test will be used to assess the assumption of normality. Categorical data will be presented as number (%). Data will be analyzed using the Chi-square test to compare percentages, t-Student test will be used to compare the means and Mann-Whitney test to compare non parametric data. Logistic regression analysis will be employed to construct a model predicting BCRL using factors regarding the patient [age, gender, BMI, American Society of Anesthesiology (ASA) classification], the tumor (size, stage, bio-molecular characteristics ), crossover, type of intervention (preservation of ARM lymph node vs. dissection), and post-operative treatment (chemotherapy, radiotherapy). Significance will be considered for values of p<0.05. Statistical analysis will be performed with IBM SPSS Statistics for Windows, Version 24.0 (IBM Corp. Armonk, NY: IBM Corp.).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| ARM lymph node preservation | Experimental | Procedure: Axillary Reverse Mapping (ARM)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. |
| ARM lymph node removal | Active comparator | Procedure: Axillary Reverse Mapping (ARM)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- T1-T2 stage breast cancer
Key exclusion criteria (7 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Axillary Reverse Mapping (ARM)ARM lymph node preservation versus removal | Procedure or surgery | ARM lymph node preservation, ARM lymph node removal |
Primary outcome
Incidence of Breast Cancer Related Lymphedema (BCRL) after Axillary Lymph Node Dissection (ALND)
Time frame: From the day of surgery to 12 months after surgery
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.
3 secondary outcomes
Incidence of Breast Cancer Related Lymphedema (BCRL) after Sentinel Lymph Node Biopsy (SLNB) alone
Time frame: From the day of surgery to 12 months after surgery
Crossover between Sentinel Lymph Node (SLN) of the Breast and the ARM lymph node
Time frame: Intraoperatively
Lymphoscintigraphic sub-clinical modifications of arm lymphatic drainage after ALND
Time frame: The day before ALND and at 60 days after ALND
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2018.
- Background: PubMed 17187979Sakorafas 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.
- Background: PubMed 15968692McWayne 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.
- Background: PubMed 15994144Purushotham 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.
- Background: PubMed 16514477Wilke 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.
- Background: PubMed 19289624Shih 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.
- Background: PubMed 17990039Ponzone 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.
- Background: PubMed 19800452Boneti 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.
- Background: PubMed 19319006Britton 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.
- Background: PubMed 21913193Noguchi 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.
- Background: PubMed 26919589Han 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.
- Background: PubMed 25776198Yue 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.
- Background: PubMed 28331338Sarri 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.
- Individual participant dataSharing planned: Undecided. Formal requests will be evaluated.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Axillary Reverse Mapping (ARM) in people with Breast Cancer Lymphedema, run by University Hospital of Ferrara at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Paolo Carcoforo, MD (0039 0532 236123, paolo.carcoforo@unife.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Breast Cancer Related Lymphedema (BCRL) after Axillary Lymph Node Dissection (ALND) (time frame: From the day of surgery to 12 months after surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03333226, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2018; AzTrials last refreshed its copy on 6 Nov 2026.