BMJ Open (Feb 2025)
The LYMPH trial: comparing microsurgical with conservative treatment for chronic breast cancer-associated lymphoedema – study protocol of a pragmatic randomised international multicentre superiority trial
- Andrea L Pusic,
- Matthias Schwenkglenks,
- Karin Ribi,
- Jane Shaw,
- Shan Shan Qiu,
- Walter Weber,
- Martin Halle,
- Khalil Zaman,
- Raymund E Horch,
- Marco Cattaneo,
- Cristina Granziera,
- Elisabeth A Kappos,
- Alexandra Schulz,
- Yves Harder,
- Rosine Mucklow,
- Martin Haug,
- Lars Hemkens,
- Daniel Staub,
- Marcus Vetter,
- Jaume Masia Ayala,
- Gemma Pons,
- Yvonne Haas,
- Florian Peters,
- Shakuntala Savanthrapadian,
- Julia Stoffel,
- Maria C Katapodi,
- Benedict Kaiser,
- Alexander Haumer,
- Stephanie Etter,
- Tristan M Handschin,
- Steffen Eisenhardt,
- Giuseppe Visconti,
- Gianluca Franceschini,
- Lorenzo Scardina,
- Benedetto Longo,
- Jan A Plock,
- Mario Scaglioni,
- Eduardo G Gonzalez,
- Sergio D Quildrian,
- Gunther Felmerer,
- Babak J Mehrara,
- Daniel F Kalbermatten,
- Justin M Sacks,
- Maximillian V Muntean,
- Erin M Taylor,
- Maria Mani,
- Florian J Jung,
- Pietro G di Summa,
- Efterpi Demiri,
- Dimitris Dionyssiou,
- Anne K Groth,
- Norbert Heine,
- Joshua Vorstenborsch,
- Kathryn V Isaac,
- Patricia E Engels,
- Axelle Serre,
- Anna-Lena Eberhardt,
- Sonja Ebner,
- Yvette Stoel,
- Cornelia Leo,
- Phillip Blondeel,
- Bjoern Behr,
- Ulrich Kneser,
- Lukas Prantl,
- Daniel T Boll,
- Nicole Lindenblatt,
- Dirk J Schaefer,
- Christoph Hirche,
- Katrin Seidenstuecker
Affiliations
- Andrea L Pusic
- 25 Division of Plastic and Reconstructive Surgery, Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Matthias Schwenkglenks
- 37 Health Economics Facility, Department of Public Health, University of Basel, Basel, Switzerland
- Karin Ribi
- 7 Quality of Life Office, International Breast Cancer Study Group, A Division of ETOP IBCSG Partners Foundation, Careum, Bern, Switzerland
- Jane Shaw
- 5 Patient Advocacy Group, Oncoplastic Breast Consortium, Basel, Switzerland
- Shan Shan Qiu
- 34 Department of Plastic, Reconstructive and Hand Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands
- Walter Weber
- 2 University of Basel, Basel, Switzerland
- Martin Halle
- 23 Department of Reconstructive Plastic Surgery, Karolinska University Hospital, Stockholm, Sweden
- Khalil Zaman
- 13 Department of Medical Oncology, Lausanne University Hospital, Lausanne, Switzerland
- Raymund E Horch
- 41 Department of Plastic and Hand Surgery, Erlangen University Hospital, Erlangen, Germany
- Marco Cattaneo
- 3 Department of Clinical Research, University Hospital Basel, Basel, Switzerland
- Cristina Granziera
- 47 Neurology Clinic and Policlinic, Departments of Head, Spine and Neuromedicine, Biomedicine and Clinical Research, University Hospital Basel, Basel, Switzerland
- Elisabeth A Kappos
- 1 Department of Plastic, Reconstructive, Aesthetic and Handsurgery, University Hospital Basel, Basel, Switzerland
- Alexandra Schulz
- 2 University of Basel, Basel, Switzerland
- Yves Harder
- 28 Department of Plastic and Hand Surgery, CHUV, Lausanne, Switzerland
- Rosine Mucklow
- 5 Patient Advocacy Group, Oncoplastic Breast Consortium, Basel, Switzerland
- Martin Haug
- 1 Department of Plastic, Reconstructive, Aesthetic and Handsurgery, University Hospital Basel, Basel, Switzerland
- Lars Hemkens
- 3 Department of Clinical Research, University Hospital Basel, Basel, Switzerland
- Daniel Staub
- 6 Department of Angiology, University Hospital Basel, Basel, Switzerland
- Marcus Vetter
- 12 Department of Oncology, Cantonal Hospital Basel-Landschaft, Liestal, Switzerland
- Jaume Masia Ayala
- 20 Department of Plastic Surgery, Universitat Autònoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- Gemma Pons
- 20 Department of Plastic Surgery, Universitat Autònoma de Barcelona, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
- Yvonne Haas
- 1 Department of Plastic, Reconstructive, Aesthetic and Handsurgery, University Hospital Basel, Basel, Switzerland
- Florian Peters
- 3 Department of Clinical Research, University Hospital Basel, Basel, Switzerland
- Shakuntala Savanthrapadian
- 2 University of Basel, Basel, Switzerland
- Julia Stoffel
- 1 Department of Plastic, Reconstructive, Aesthetic and Handsurgery, University Hospital Basel, Basel, Switzerland
- Maria C Katapodi
- 4 Department of Clinical Research, Founding Member Patient Advocacy Group Oncoplastic Breast Consortium, University Hospital Basel, Basel, Switzerland
- Benedict Kaiser
- 1 Department of Plastic, Reconstructive, Aesthetic and Handsurgery, University Hospital Basel, Basel, Switzerland
- Alexander Haumer
- 1 Department of Plastic, Reconstructive, Aesthetic and Handsurgery, University Hospital Basel, Basel, Switzerland
- Stephanie Etter
- 1 Department of Plastic, Reconstructive, Aesthetic and Handsurgery, University Hospital Basel, Basel, Switzerland
- Tristan M Handschin
- 1 Department of Plastic, Reconstructive, Aesthetic and Handsurgery, University Hospital Basel, Basel, Switzerland
- Steffen Eisenhardt
- 8 Department of Plastic and Hand Surgery, University Hospital Freiburg, Freiburg, Germany
- Giuseppe Visconti
- 9 Department of Woman and Child Health and Public Health, Division of Plastic Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Gianluca Franceschini
- 10 Department of Woman, Child Health and Public Health, Division of Breast Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Lorenzo Scardina
- 10 Department of Woman, Child Health and Public Health, Division of Breast Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
- Benedetto Longo
- 11 Department of Plastic and Reconstructive Surgery, University of Rome Tor Vergata, Roma, Italy
- Jan A Plock
- 14 Department of Plastic Surgery and Hand Surgery, Cantonal Hospital Aarau, Aarau, Switzerland
- Mario Scaglioni
- 15 Department of Hand and Plastic Surgery, Cantonal Hospital Lucerne, Lucerne, Switzerland
- Eduardo G Gonzalez
- 17 Division of Oncoplastic Surgery, Buenos Aires British Hospital, University of Buenos Aires, Instituto de Oncología Angel H Roffo, Buenos Aires, Argentina
- Sergio D Quildrian
- 17 Division of Oncoplastic Surgery, Buenos Aires British Hospital, University of Buenos Aires, Instituto de Oncología Angel H Roffo, Buenos Aires, Argentina
- Gunther Felmerer
- 18 Department of Trauma Surgery, Orthopedic Surgery and Plastic Surgery, University Medical Center Göttingen, Gottingen, Germany
- Babak J Mehrara
- 19 Department of Plastic and Reconstructive Surgery, Memorial Sloan Kettering Cancer Center, New York City, New York, USA
- Daniel F Kalbermatten
- 21 Department of Plastic, Reconstructive, and Aesthetic Surgery, Geneva University Hospitals, Geneva, Switzerland
- Justin M Sacks
- 22 Division of Plastic and Reconstructive Surgery, Washington University School of Medicine in Saint Louis, St Louis, Missouri, USA
- Maximillian V Muntean
- 24 Department of Plastic Surgery, Institute of Oncology, University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca, Romania
- Erin M Taylor
- 25 Division of Plastic and Reconstructive Surgery, Department of Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
- Maria Mani
- 26 Department of Plastic and Maxillofacial Surgery, Uppsala University Hospital, Uppsala, Sweden
- Florian J Jung
- 27 Department of Plastic and Hand Surgery, Cantonal Hospital Winterthur, Winterthur, Switzerland
- Pietro G di Summa
- 28 Department of Plastic and Hand Surgery, CHUV, Lausanne, Switzerland
- Efterpi Demiri
- 29 Department of Plastic Surgery, Aristotle University of Thessaloniki, Thessaloniki, Greece
- Dimitris Dionyssiou
- 29 Department of Plastic Surgery, Aristotle University of Thessaloniki, Thessaloniki, Greece
- Anne K Groth
- 30 Department of Plastic Surgery, Hospital Erasto Gaertner, Curitiba, Brazil
- Norbert Heine
- 31 Department of Plastic Surgery, Caritas Hospital St. Josef, Regensburg, Germany
- Joshua Vorstenborsch
- 32 Division of Plastic Surgery, McGill University, Montreal, Québec, Canada
- Kathryn V Isaac
- 33 Division of Plastic Surgery, The University of British Columbia, Vancouver, British Columbia, Canada
- Patricia E Engels
- 21 Department of Plastic, Reconstructive, and Aesthetic Surgery, Geneva University Hospitals, Geneva, Switzerland
- Axelle Serre
- 21 Department of Plastic, Reconstructive, and Aesthetic Surgery, Geneva University Hospitals, Geneva, Switzerland
- Anna-Lena Eberhardt
- 35 Department of Radiation Oncology, University Hospital Basel, Basel, Switzerland
- Sonja Ebner
- 36 Department of Obstetrics and Gynecology, Cantonal Hospital Basel-Landschaft, Liestal, Switzerland
- Yvette Stoel
- 39 Institute of Therapies and Rehabilitation, Division of Physiotherapy, Cantonal Hospital Winterthur, Winterthur, Switzerland
- Cornelia Leo
- 40 Breast Center, Kantonsspital Baden AG, Baden, Switzerland
- Phillip Blondeel
- 42 Department of Plastic and Reconstructive Surgery, University Hospital Ghent, Gent, Belgium
- Bjoern Behr
- 43 Department of Plastic, Reconstructive and Aesthetic Surgery, KEM Kliniken Essen-Mitte, Essen, Germany
- Ulrich Kneser
- 44 Department of Hand, Plastic and Reconstructive Surgery, Burn Center, University Hospital Heidelberg, BG Klinik Ludwigshafen, Ludwigshafen, Germany
- Lukas Prantl
- 45 Department of Plastic Surgery, University Hospital Regensburg, Regensburg, Germany
- Daniel T Boll
- 46 Department of Radiology and Nuclear Medicine, University Hospital Basel, Basel, Switzerland
- Nicole Lindenblatt
- 51 Department of Plastic and Hand Surgery, University Hospital Zurich, Zurich, Switzerland
- Dirk J Schaefer
- 1 Department of Plastic, Reconstructive, Aesthetic and Handsurgery, University Hospital Basel, Basel, Switzerland
- Christoph Hirche
- 52 Department of Plastic, Hand and Reconstructive Microsurgery, Hand Trauma and Replantation Centre, BG Unfallklinik Frankfurt am Main, Frankfurt am Main, Germany
- Katrin Seidenstuecker
- 53 Department of Plastic Surgery, Sana Kliniken Düsseldorf GmbH, Dusseldorf, Germany
- DOI
- https://doi.org/10.1136/bmjopen-2024-090662
- Journal volume & issue
-
Vol. 15,
no. 2
Abstract
Introduction Up to one-fifth of breast cancer survivors will develop chronic breast cancer-related lymphoedema (BCRL). To date, complex physical decongestion therapy (CDT) is the gold standard of treatment. However, it is mainly symptomatic and often ineffective in preventing BCRL progression. Lymphovenous anastomosis (LVA) and vascularised lymph node transfer (VLNT) are microsurgical techniques that aim to restore lymphatic drainage. This international randomised trial aims to evaluate advantages of microsurgical interventions plus CDT versus CDT alone for BCRL treatment.Methods and analysis The effectiveness of LVA and/or VLNT in combination with CDT, which may be combined with liposuction, versus CDT alone will be evaluated in routine practice across the globe. Patients with BCRL will be randomly allocated to either surgical or conservative therapy. The primary end point of this trial is the patient-reported quality of life (QoL) outcome ‘lymphoedema-specific QoL’, which will be assessed 15 months after randomisation. Secondary end points are further patient-reported outcomes (PROs), arm volume measurements, economic evaluations and imaging at different time points. A long-term follow-up will be conducted up to 10 years after randomisation. A total of 280 patients will be recruited in over 20 sites worldwide.Ethics and dissemination This study will be conducted in compliance with the Declaration of Helsinki and the International Council for Harmonisation-Good Clinical Practice (ICH-GCP) E6 guideline. Ethical approval has been obtained by the lead ethics committee ‘Ethikkommission Nordwest- und Zentralschweiz’ (2023-00733, 22 May 2023). Ethical approval from local authorities will be sought for all participating sites. Regardless of outcomes, the findings will be published in a peer-reviewed medical journal. Metadata detailing the dataset’s type, size and content will be made available, along with the full study protocol and case report forms, in public repositories in compliance with the Findability, Accessibility, Interoperability and Reuse principles.Trial registration number NCT05890677.
