Who and Why do Patients Report Lymphedema After Breast Cancer Treatment Without an Objective Measurable Swelling

Official title

The Enigma of Subjective Lymphedema: Who and Why do Patients Report Lymphedema After Breast Cancer Treatment Without an Objective Measurable Swelling? The Role of Lymphatic and Sensory Processing Problems

Overview

Breast cancer related lymphedema (BCRL) at the arm and/or trunk is an extremely dreaded complication after breast cancer treatment due to its chronicity and impact. The incidence of objective arm and trunk/ breast BCRL is declining due to the major shift into the treatment approach of breast cancer. However, many patients report a sensation of swelling without the presence of objective BCRL, referred to as subjective BCRL. Therefore, subjective BCRL is defined as the diagnosis of BCRL based on the patient's sensation of a difference in size at the arm and/or trunk without the presence of objective BCRL. At this moment, there is no clear information on the prevalence and the transitions between different BCRL states (no-subjective-objective) over time, as well as about the underlying mechanisms and contributing factors of subjective BCRL. Therefore, the investigators hypothesize that four mechanisms might be associated with the presence and severity of subjective arm or trunk/breast BCRL, including the presence and/ or severity of lymphatic (1) and sensory processing problems (nociceptive (2), neuropathic (3), and/or central sensory processing problems (4)). The investigators will set up a prospective longitudinal study with breast cancer patients to determine the prevalence of subjective and objective arm or trunk/ breast BCRL at 1, 6, and 12 month(s) post-surgery and the transitions between different BCRL states (no-subjective-objective BCRL) (AIM 1). In addition, factors related to four potential underlying mechanisms (lymphatic, nociceptive, neuropathic, and central sensory processing problems) that contribute to the occurrence of subjective BCRL in comparison to no self-reported swelling and objective BCRL will be determined (AIM 2). Furthermore, the present study will be undertaken to determine factors related to these four underlying mechanisms that contribute to the severity of subjective BCRL at arm or trunk/ breast BCRL within the group of patients with subjective BCRL at different time-points after surgery (at 1, 6, and 12 month(s) post-surgery) (AIM 3).

Interventions

• Other Measurements for breast cancer related lymphedema (volumetric measurements, bioimpedance spectroscopy, bioimpedance analysis, tissue dielectric constant measurements, ultrasonography)
  Assessments related to different types of breast cancer related lymphedema at arm (1. self-reported swelling at arm, 2. subjective arm lymphedema, 3. objective arm lymphedema) using the Norman questionnaire, volume measurements (volumetry and perimetry), bioimpedance spectroscopy, and bioimpedance analysis Assessments related to different types of breast cancer related lymphedema at trunk/ breast (1. self-reported swelling at trunk/ breast, 2. subjective trunk/ breast lymphedema, 3. objective t
• Other Measurements for lymphatic problems (volumetric measurements, tissue dielectric measurement, lymphofluoroscopy)
  Clinical assessments related to lymphatic problems (1. amount of swelling at arm by relative arm volume difference, 2. amount of swelling at trunk by percentage water ratio, 3. severity of dermal rerouting at upper limb and trunk by lymphofluoroscopy (i.e., near-infrared fluorescence imaging device)
• Other Measurements for sensory processing problems by monofilaments, algometer, goniometer, and neurosensory analyzer
  Clinical measurements related to nociceptive, neuropathic and central sensory problems based on the Quantitative Sensory Testing principles using different devices algometer, goniometer, standardized set of monofilaments, and neurosensory analyzer

Primary outcome measures

• Presence of subjective arm lymphedema [Time frame: Time frame up to 12 months post-surgery]
• Presence of subjective trunk/ breast lymphedema [Time frame: Time frame up to 12 months post-surgery]
• Presence of objective arm lymphedema [Time frame: Time frame up to 12 months post-surgery]
• Presence of objective trunk/ breast lymphedema [Time frame: Time frame up to 12 months post-surgery]

Secondary outcome measures (12)

• Amount of swelling at upper limb and trunk/breast [Time frame: Time frame up to 12 months post-surgery]
• Severity of dermal rerouting at upper limb and trunk/breast [Time frame: Time frame up to 12 months post-surgery]
• Severity of myofascial adhesions at the level of the scars [Time frame: Time frame up to 12 months post-surgery]
• Severity of local muscle stiffness [Time frame: Time frame up to 12 months post-surgery]
• Severity of local muscle tenderness [Time frame: Time frame up to 12 months post-surgery]
• Severity of impaired shoulder range of motion [Time frame: Time frame up to 12 months post-surgery]
• Presence of neuropathic pain at upper arm and trunk [Time frame: Time frame up to 12 months post-surgery]
• Severity of sensory loss at the arm and trunk [Time frame: Time frame up to 12 months post-surgery]
• Severity of altered cold sensation sensitivity at the arm and trunk [Time frame: Time frame up to 12 months post-surgery]
• Severity of altered heat sensation sensitivity at the arm and trunk [Time frame: Time frame up to 12 months post-surgery]
• Severity of altered sensory acuity in the arm and trunk [Time frame: Time frame up to 12 months post-surgery]
• Severity of widespread hyperalgesia [Time frame: Time frame up to 12 months post-surgery]

Eligibility criteria

Inclusion criteria

• adults (men and women) who are ≥ 18 years of age
• diagnosed with primary unilateral non-metastatic or oligometastatic breast cancer
• scheduled for surgery (mastectomy or breast conserving surgery; in combination with axillary lymph node dissection or sentinel node biopsy)
• able to read, understand, and speak Dutch
• have voluntary written informed consent of the patient

Exclusion criteria

• distant metastases
• planned bilateral lymph node surgery
• oedema of the arm from another cause
• an allergy to iodine or Indocyanine Green (ICG), or
• physically or mentally unable to participate throughout the entire duration of the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Screening

Study locations

Belgium · 1 center

• University Hospitals of Leuven, center for lymphedema — Leuven

Publications

• Gursen C, Dylke ES, Moloney N, Meeus M, De Vrieze T, Devoogdt N, De Groef A. Self-reported signs and symptoms of secondary upper limb lymphoedema related to breast cancer treatment: Systematic review. Eur J Cancer Care (Engl). 2021 Sep;30(5):e13440. doi: 10.1111/ecc.13440. Epub 2021 Mar 18. PMID 33733550
• Svensson BJ, Dylke ES, Ward LC, Black DA, Kilbreath SL. Screening for breast cancer-related lymphoedema: self-assessment of symptoms and signs. Support Care Cancer. 2020 Jul;28(7):3073-3080. doi: 10.1007/s00520-019-05083-7. Epub 2019 Oct 22. PMID 31641870
• De Groef A, Devoogdt N, Gursen C, Moloney N, Warpy V, Daelemans J, Dams L, Haenen V, Van der Gucht E, Heroes AK, De Vrieze T, Dylke E. Correction to: Sensory signs and symptoms in women with self-reported breast cancer-related lymphedema: a case-control study. J Cancer Surviv. 2022 Dec;16(6):1508-1509. doi: 10.1007/s11764-021-01125-4. No abstract available. PMID 34716888
• Fu MR, Axelrod D, Cleland CM, Qiu Z, Guth AA, Kleinman R, Scagliola J, Haber J. Symptom report in detecting breast cancer-related lymphedema. Breast Cancer (Dove Med Press). 2015 Oct 15;7:345-52. doi: 10.2147/BCTT.S87854. eCollection 2015. PMID 26527899
• Sackey H, Johansson H, Sandelin K, Liljegren G, MacLean G, Frisell J, Brandberg Y. Self-perceived, but not objective lymphoedema is associated with decreased long-term health-related quality of life after breast cancer surgery. Eur J Surg Oncol. 2015 Apr;41(4):577-84. doi: 10.1016/j.ejso.2014.12.006. Epub 2015 Jan 13. PMID 25659877
• Terada M, Yoshimura A, Sawaki M, Hattori M, Naomi G, Kotani H, Adachi Y, Iwase M, Kataoka A, Sugino K, Mori M, Horisawa N, Ozaki Y, Iwata H. Patient-reported outcomes and objective assessments with arm measurement and bioimpedance analysis for lymphedema among breast cancer survivors. Breast Cancer Res Treat. 2020 Jan;179(1):91-100. doi: 10.1007/s10549-019-05443-1. Epub 2019 Sep 18. PMID 31535321
• Sayko O, Pezzin LE, Yen TW, Nattinger AB. Diagnosis and treatment of lymphedema after breast cancer: a population-based study. PM R. 2013 Nov;5(11):915-23. doi: 10.1016/j.pmrj.2013.05.005. Epub 2013 May 17. PMID 23684778
• McLaughlin SA, Wright MJ, Morris KT, Sampson MR, Brockway JP, Hurley KE, Riedel ER, Van Zee KJ. Prevalence of lymphedema in women with breast cancer 5 years after sentinel lymph node biopsy or axillary dissection: patient perceptions and precautionary behaviors. J Clin Oncol. 2008 Nov 10;26(32):5220-6. doi: 10.1200/JCO.2008.16.3766. Epub 2008 Oct 6. PMID 18838708

Identifiers

NCT: NCT06324721 · S68133

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗