The LYMPH trial: comparing microsurgical with conservative treatment for chronic breast cancer-associated lymphoedema - study protocol of a pragmatic randomised international multicentre superiority trial

Elisabeth A. Kappos; Yvonne Haas; Alexandra Schulz; Florian Peters; Shakuntala Savanthrapadian; Julia Stoffel; Maria C. Katapodi; Rosine Mucklow; Benedict Kaiser; Alexander Haumer; Stephanie Etter; Marco Cattaneo; Daniel Staub; Karin Ribi; Jane Shaw; Tristan M. Handschin; Steffen Eisenhardt; Giuseppe Visconti; Gianluca Franceschini; Lorenzo Scardina; Benedetto Longo; Marcus Vetter; Khalil Zaman; Jan A. Plock; Mario Scaglioni; Eduardo G. Gonzalez; Sergio D. Quildrian; Gunther Felmerer; Babak J. Mehrara; Jaume Masia Ayala; Gemma Pons; Daniel F. Kalbermatten; Justin M. Sacks; Martin Halle; 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; Shan Shan Qiu; Patricia E. Engels; Axelle Serre; Anna Lena Eberhardt; Sonja Ebner; Matthias Schwenkglenks; Yvette Stoel; Cornelia Leo; Raymund E. Horch; Phillip Blondeel; Bjoern Behr; Ulrich Kneser; Lukas Prantl; Daniel T. Boll; Cristina Granziera; Lars Hemkens; Nicole Lindenblatt; Martin Haug; Dirk J. Schaefer; Christoph Hirche; Andrea L. Pusic; Katrin Seidenstuecker; Yves Harder; Walter Weber

doi:10.1136/bmjopen-2024-090662

The LYMPH trial: comparing microsurgical with conservative treatment for chronic breast cancer-associated lymphoedema - study protocol of a pragmatic randomised international multicentre superiority trial

Elisabeth A. Kappos, Yvonne Haas, Alexandra Schulz, Florian Peters, Shakuntala Savanthrapadian, Julia Stoffel, Maria C. Katapodi, Rosine Mucklow, Benedict Kaiser, Alexander Haumer, Stephanie Etter, Marco Cattaneo, Daniel Staub, Karin Ribi, Jane Shaw, Tristan M. Handschin, Steffen Eisenhardt, Giuseppe Visconti, Gianluca Franceschini, Lorenzo ScardinaBenedetto Longo, Marcus Vetter, Khalil Zaman, Jan A. Plock, Mario Scaglioni, Eduardo G. Gonzalez, Sergio D. Quildrian, Gunther Felmerer, Babak J. Mehrara, Jaume Masia Ayala, Gemma Pons, Daniel F. Kalbermatten, Justin M. Sacks, Martin Halle, 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, Shan Shan Qiu, Patricia E. Engels, Axelle Serre, Anna Lena Eberhardt, Sonja Ebner, Matthias Schwenkglenks, Yvette Stoel, Cornelia Leo, Raymund E. Horch, Phillip Blondeel, Bjoern Behr, Ulrich Kneser, Lukas Prantl, Daniel T. Boll, Cristina Granziera, Lars Hemkens, Nicole Lindenblatt, Martin Haug, Dirk J. Schaefer, Christoph Hirche, Andrea L. Pusic, Katrin Seidenstuecker, Yves Harder, Walter Weber

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	e090662
Journal	BMJ Open
Volume	15
Issue number	2
DOIs	https://doi.org/10.1136/bmjopen-2024-090662
State	Published - Feb 17 2025

Keywords

breast tumours
clinical trial
patient reported outcome measures
plastic & reconstructive surgery
plastic & reconstructive surgery
randomized controlled trial

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Kappos, E. A., Haas, Y., Schulz, A., Peters, F., Savanthrapadian, S., Stoffel, J., Katapodi, M. C., Mucklow, R., Kaiser, B., Haumer, A., Etter, S., Cattaneo, M., Staub, D., Ribi, K., Shaw, J., Handschin, T. M., Eisenhardt, S., Visconti, G., Franceschini, G., ... Weber, W. (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. BMJ Open, 15(2), Article e090662. https://doi.org/10.1136/bmjopen-2024-090662

@article{22d10c7c3d10494b8a040b11a822e5a1,

title = "The LYMPH trial: comparing microsurgical with conservative treatment for chronic breast cancer-associated lymphoedema - study protocol of a pragmatic randomised international multicentre superiority trial",

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.",

keywords = "breast tumours, clinical trial, patient reported outcome measures, plastic & reconstructive surgery, plastic & reconstructive surgery, randomized controlled trial",

author = "Kappos, {Elisabeth A.} and Yvonne Haas and Alexandra Schulz and Florian Peters and Shakuntala Savanthrapadian and Julia Stoffel and Katapodi, {Maria C.} and Rosine Mucklow and Benedict Kaiser and Alexander Haumer and Stephanie Etter and Marco Cattaneo and Daniel Staub and Karin Ribi and Jane Shaw and Handschin, {Tristan M.} and Steffen Eisenhardt and Giuseppe Visconti and Gianluca Franceschini and Lorenzo Scardina and Benedetto Longo and Marcus Vetter and Khalil Zaman and Plock, {Jan A.} and Mario Scaglioni and Gonzalez, {Eduardo G.} and Quildrian, {Sergio D.} and Gunther Felmerer and Mehrara, {Babak J.} and Ayala, {Jaume Masia} and Gemma Pons and Kalbermatten, {Daniel F.} and Sacks, {Justin M.} and Martin Halle and Muntean, {Maximillian V.} and Taylor, {Erin M.} and Maria Mani and Jung, {Florian J.} and {Di Summa}, {Pietro G.} and Efterpi Demiri and Dimitris Dionyssiou and Groth, {Anne K.} and Norbert Heine and Joshua Vorstenborsch and Isaac, {Kathryn V.} and Qiu, {Shan Shan} and Engels, {Patricia E.} and Axelle Serre and Eberhardt, {Anna Lena} and Sonja Ebner and Matthias Schwenkglenks and Yvette Stoel and Cornelia Leo and Horch, {Raymund E.} and Phillip Blondeel and Bjoern Behr and Ulrich Kneser and Lukas Prantl and Boll, {Daniel T.} and Cristina Granziera and Lars Hemkens and Nicole Lindenblatt and Martin Haug and Schaefer, {Dirk J.} and Christoph Hirche and Pusic, {Andrea L.} and Katrin Seidenstuecker and Yves Harder and Walter Weber",

note = "Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.",

year = "2025",

month = feb,

day = "17",

doi = "10.1136/bmjopen-2024-090662",

language = "English",

volume = "15",

journal = "BMJ Open",

issn = "2044-6055",

number = "2",

}

Kappos, EA, Haas, Y, Schulz, A, Peters, F, Savanthrapadian, S, Stoffel, J, Katapodi, MC, Mucklow, R, Kaiser, B, Haumer, A, Etter, S, Cattaneo, M, Staub, D, Ribi, K, Shaw, J, Handschin, TM, Eisenhardt, S, Visconti, G, Franceschini, G, Scardina, L, Longo, B, Vetter, M, Zaman, K, Plock, JA, Scaglioni, M, Gonzalez, EG, Quildrian, SD, Felmerer, G, Mehrara, BJ, Ayala, JM, Pons, G, Kalbermatten, DF, Sacks, JM, Halle, M, Muntean, MV, Taylor, EM, Mani, M, Jung, FJ, Di Summa, PG, Demiri, E, Dionyssiou, D, Groth, AK, Heine, N, Vorstenborsch, J, Isaac, KV, Qiu, SS, Engels, PE, Serre, A, Eberhardt, AL, Ebner, S, Schwenkglenks, M, Stoel, Y, Leo, C, Horch, RE, Blondeel, P, Behr, B, Kneser, U, Prantl, L, Boll, DT, Granziera, C, Hemkens, L, Lindenblatt, N, Haug, M, Schaefer, DJ, Hirche, C, Pusic, AL, Seidenstuecker, K, Harder, Y & Weber, W 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', BMJ Open, vol. 15, no. 2, e090662. https://doi.org/10.1136/bmjopen-2024-090662

The LYMPH trial: comparing microsurgical with conservative treatment for chronic breast cancer-associated lymphoedema - study protocol of a pragmatic randomised international multicentre superiority trial. / Kappos, Elisabeth A.; Haas, Yvonne; Schulz, Alexandra et al.
In: BMJ Open, Vol. 15, No. 2, e090662, 17.02.2025.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - The LYMPH trial

T2 - comparing microsurgical with conservative treatment for chronic breast cancer-associated lymphoedema - study protocol of a pragmatic randomised international multicentre superiority trial

AU - Kappos, Elisabeth A.

AU - Haas, Yvonne

AU - Schulz, Alexandra

AU - Peters, Florian

AU - Savanthrapadian, Shakuntala

AU - Stoffel, Julia

AU - Katapodi, Maria C.

AU - Mucklow, Rosine

AU - Kaiser, Benedict

AU - Haumer, Alexander

AU - Etter, Stephanie

AU - Cattaneo, Marco

AU - Staub, Daniel

AU - Ribi, Karin

AU - Shaw, Jane

AU - Handschin, Tristan M.

AU - Eisenhardt, Steffen

AU - Visconti, Giuseppe

AU - Franceschini, Gianluca

AU - Scardina, Lorenzo

AU - Longo, Benedetto

AU - Vetter, Marcus

AU - Zaman, Khalil

AU - Plock, Jan A.

AU - Scaglioni, Mario

AU - Gonzalez, Eduardo G.

AU - Quildrian, Sergio D.

AU - Felmerer, Gunther

AU - Mehrara, Babak J.

AU - Ayala, Jaume Masia

AU - Pons, Gemma

AU - Kalbermatten, Daniel F.

AU - Sacks, Justin M.

AU - Halle, Martin

AU - Muntean, Maximillian V.

AU - Taylor, Erin M.

AU - Mani, Maria

AU - Jung, Florian J.

AU - Di Summa, Pietro G.

AU - Demiri, Efterpi

AU - Dionyssiou, Dimitris

AU - Groth, Anne K.

AU - Heine, Norbert

AU - Vorstenborsch, Joshua

AU - Isaac, Kathryn V.

AU - Qiu, Shan Shan

AU - Engels, Patricia E.

AU - Serre, Axelle

AU - Eberhardt, Anna Lena

AU - Ebner, Sonja

AU - Schwenkglenks, Matthias

AU - Stoel, Yvette

AU - Leo, Cornelia

AU - Horch, Raymund E.

AU - Blondeel, Phillip

AU - Behr, Bjoern

AU - Kneser, Ulrich

AU - Prantl, Lukas

AU - Boll, Daniel T.

AU - Granziera, Cristina

AU - Hemkens, Lars

AU - Lindenblatt, Nicole

AU - Haug, Martin

AU - Schaefer, Dirk J.

AU - Hirche, Christoph

AU - Pusic, Andrea L.

AU - Seidenstuecker, Katrin

AU - Harder, Yves

AU - Weber, Walter

PY - 2025/2/17

Y1 - 2025/2/17

N2 - 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.

AB - 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.

KW - breast tumours

KW - clinical trial

KW - patient reported outcome measures

KW - plastic & reconstructive surgery

KW - randomized controlled trial

UR - http://www.scopus.com/inward/record.url?scp=85218930477&partnerID=8YFLogxK

U2 - 10.1136/bmjopen-2024-090662

DO - 10.1136/bmjopen-2024-090662

M3 - Article

C2 - 39961719

AN - SCOPUS:85218930477

SN - 2044-6055

VL - 15

JO - BMJ Open

JF - BMJ Open

IS - 2

M1 - e090662

ER -

The LYMPH trial: comparing microsurgical with conservative treatment for chronic breast cancer-associated lymphoedema - study protocol of a pragmatic randomised international multicentre superiority trial

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