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Secondary lymphedema from cancer therapy

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Abstract

This manuscript is a summary of findings focusing on various aspects of secondary lymphedema specifically as a sequelae of treatment for cancer. The topic was addressed at a session held during the 8th International Congress on Cancer Metastasis that was unique a for the inclusion of patients with lymphedema and therapists joining physicians, healthcare professionals, and researchers in an effort to give an overview of secondary lymphedema following cancer therapy as well as highlighting the unknowns in the field. Lymphedema is defined and both diagnosis and incidence of cancer-related lymphedema are explored. Further, exploration of imaging options for lymphedema and information on the genetic research for patients with cancer-related secondary lymphedema are presented. Patient education and early detection methods are then explored followed by conservative treatment. Finally, an examination of surgical treatment methods available for patients with lymphedema is covered. Overall, this manuscript presents valuable information and updates for those not familiar with incidence, diagnosis, early detection, and rehabilitation of patients with cancer-related secondary lymphedema.

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References

  1. International Society of Lymphology (2020) The diagnosis and treatment of peripheral lymphedema: 2020 consensus document of the international society of lymphology. Lymphology 53:3–19

    Google Scholar 

  2. Cormier JN, Askew RL, Mungovan KS, Xing Y, Ross MI, Armer JM (2010) Lymphedema beyond breast cancer: a systematic review and meta-analysis of cancer-related secondary lymphedema. Cancer 116(22):5138–5149

    Article  Google Scholar 

  3. Shaitelman SF, Cromwell KD, Rasmussen JC, Stout NL, Armer JM, Lasinski BB, Cormier JN (2014) Recent progress in the treatment and prevention of cancer-related lymphedema. CA Cancer J Clin 65:55–81

    Article  Google Scholar 

  4. Tandra P, Kallam A, Krishnamurthy J (2019) Identification and management of lymphedema in patients with breast cancer. J Oncol Pract 15(5):255–262. https://doi.org/10.1200/JOP.18.00141

    Article  PubMed  Google Scholar 

  5. Lee MJ, Beith J, Ward L, Kilbreath S (2014) Lymphedema following taxane-based chemotherapy in women with early breast cancer. Lymphat Res Biol 12(4):282–288. https://doi.org/10.1089/lrb.2014.0030

    Article  CAS  PubMed  Google Scholar 

  6. Stanton AW, Modi S, Bennett Britton TM, Purushotham AD, Peters AM, Levick JR, Mortimer PS (2009) Lymphatic drainage in the muscle and subcutis of the arm after breast cancer treatment. Breast Cancer Res Treat 117(3):549–557. https://doi.org/10.1007/s10549-008-0259-z

    Article  PubMed  Google Scholar 

  7. Asellius G (1627) De lactibus venis quarto vasorum mesaraicorum genere novo inuento, Mediolani. JB Biddellium. Reproduced in 1972 by Epistem Editrice, Milano

  8. Natale G, Bocci G, Ribatti D (2017) Scholars and scientists in the history of the lymphatic system. J Anat 231(3):417–429

    Article  Google Scholar 

  9. Kinmonth JB (1972) The lymphatics: diseases, lymphography and surgery. Williams & Wilkins, Baltimore

    Google Scholar 

  10. Bernas M (2013) Imaging of the lymphatic system. Lymphedema management: the comprehensive guide for practitioners, 3rd edn. Thieme, New York

    Google Scholar 

  11. Witte CL, Witte MH, Unger EC, Williams WH, Bernas MJ, McNeill GC, Stazzone AM (2000) Advances in imaging of lymph flow disorders. Radiographics 20(6):1697–1719

    Article  CAS  Google Scholar 

  12. Jayaraj A, Raju S, May C, Pace N (2019) The diagnostic unreliability of classic physical signs of lymphedema. J Vasc Surg Venous Lymphat Disord 7(6):890–897. https://doi.org/10.1016/j.jvsv.2019.04.013

    Article  PubMed  Google Scholar 

  13. Rasmussen JC, Kwon S, Sevick-Muraca EM, Cormier JN (2012) The role of lymphatics in cancer as assessed by near-infrared fluorescence imaging. Ann Biomed Eng 40:408–421. https://doi.org/10.1007/s10439-011-0476-1

    Article  PubMed  Google Scholar 

  14. Hwang JH, Choi JY, Lee JY, Hyun SH, Choi Y, Choe YS, Lee KH, Kim BT (2007) Lymphscintigraphy predicts response to complex physical therapy in patients with early stage extremity lymphedema. Lymphology 40:172–176

    CAS  PubMed  Google Scholar 

  15. Yamamoto T, Matsuda N, Doi K, Oshima A, Yoshimatsu H, Todokoro T, Ogata F, Mihara M, Narushima M, Iida T, Koshima I (2011) The earliest finding of indocyanine green lymphography in asymptomatic limbs of lower extremity lymphedema patients secondary to cancer treatment: the modified dermal backflow stage and concept of subclinical lymphedema. Plast Reconstr Surg 128(4):314e–321e

    Article  CAS  Google Scholar 

  16. Yamamoto T, Yamamoto N, Doi K, Oshima A, Yoshimatsu H, Todokoro T, Ogata F, Mihara M, Narushima M, Iida T, Koshima I (2011) Indocyanine green-enhanced lymphography for upper extremity lymphedema: a novel severity staging system using dermal backflow patterns. Plast Reconstr Surg 128(4):941–947. https://doi.org/10.1097/PRS.0b013e3182268cd9

    Article  CAS  PubMed  Google Scholar 

  17. Aldrich MB, Rasmussen JC, Fife CE, Shaitelman SF, Sevick-Muraca EM (2020) The development and treatment of lymphatic dysfunction in cancer patients and survivors. Cancers (Basel) 12(8):2280. https://doi.org/10.3390/cancers12082280

    Article  CAS  Google Scholar 

  18. Dori Y, Keller MS, Fogel MA, Rome JJ, Whitehead KK, Harris MA, Itkin M (2014) MRI of lymphatic abnormalities after functional single-ventricle palliation surgery. AJR 203:426–431

    Article  Google Scholar 

  19. Dori Y (2016) Novel lymphatic imaging techniques. Tech Vasc Interv Radiol 19(4):255–261. https://doi.org/10.1053/j.tvir.2016.10.002

    Article  PubMed  Google Scholar 

  20. Rane S, Donahue PMC, Towse T, Ridner S, Chappell M, Jordi J, Gore J, Donahue MJ (2013) Clinical feasibility of noninvasive visualization of lymphatic flow with principles of spin labeling MR imaging: implications for lymphedema assessment. Radiology 269:893–902

    Article  Google Scholar 

  21. Brouillard P, Boon L, Vikkula M (2014) Genetics of lymphatic anomalies. J Clin Invest 124(3):898–904

    Article  CAS  Google Scholar 

  22. Leppänen VM, Brouillard P, Korhonen EA, Sipilä T, Jha SK, Revencu N, Labarque V, Fastré E, Schlögel M, Ravoet M, Singer A, Luzzatto C, Angelone D, Crichiutti G, D’Elia A, Kuurne J, Elamaa H, Koh GY, Saharinen P, Vikkula M, Alitalo K (2020) Characterization of ANGPT2 mutations associated with primary lymphedema. Sci Transl Med 12(560):eaax8013. https://doi.org/10.1126/scitranslmed.aax8013

    Article  CAS  PubMed  Google Scholar 

  23. Michelini S, Vettori A, Maltese PE, Cardone M, Bruson A, Fiorentino A, Cappellino F, Sainato V, Guerri G, Marceddu G, Tezzele S, Bertelli M (2016) Genetic screening in a large cohort of Italian patients affected by primary lymphedema using a next generation sequencing (NGS) approach. Lymphology 49(2):57–72

    CAS  PubMed  Google Scholar 

  24. Gordon K, Varney R, Keeley V, Riches K, Jeffery S, Van Zanten M, Mortimer P, Ostergaard P, Mansour S (2020) Update and audit of the St George’s classification algorithm of primary lymphatic anomalies: a clinical and molecular approach to diagnosis. J Med Genet 57(10):653–659. https://doi.org/10.1136/jmedgenet-2019-106084

    Article  CAS  PubMed  Google Scholar 

  25. Finegold DN, Schacht V, Kimak MA, Lawrence EC, Foeldi E, Karlsson JM, Baty CJ, Ferrell RE (2008) HGF and MET mutations in primary and secondary lymphedema. Lymphat Res Biol 6:65–68

    Article  CAS  Google Scholar 

  26. Finegold DN, Baty CJ, Knickelbein KZ, Perschke S, Noon SE, Campbell D, Karlsson JM, Huang D, Kimak MA, Lawrence EC, Feingold E, Meriney SD, Brufsky AM, Ferrell RE (2012) Connexin 47 mutations increase risk for secondary lymphedema following breast cancer treatment. Clin Cancer Res 18(8):1–9

    Article  Google Scholar 

  27. Newman B, Lose F, Kedda M-A, Francois M, Ferguson K, Janda M, Yates P, Spurdle AB, Hayes SC (2012) Possible genetic predisposition to lymphedema after breast cancer. Lymphat Res Biol 10:2–13

    Article  CAS  Google Scholar 

  28. Fu MR, Conley YP, Axelrod D, Guth AA, Yu G, Fletcher J, Zagzag D (2016) Precision assessment of heterogeneity of lymphedema phenotype, genotypes and risk prediction. Breast 29:231–240

    Article  Google Scholar 

  29. Miaskowski C, Dodd M, Paul SM, West C, Hamolsky D, Abrams G, Cooper BA, Elboim C, Neuhaus J, Schmidt BL, Smoot B, Aouizeratet BE (2013) Lymphatic and angiogenic candidate genes predict the development of secondary lymphedema following breast cancer surgery. PLoS ONE 8(4):e60164

    Article  CAS  Google Scholar 

  30. Leung G, Baggott C, West C, Elboim C, Paul SM, Cooper BA, Abrams G, Dhruva A, Schmidt BL, Kober K, Merriman JD, Leutwyler H, Neuhaus J, Langford D, Smoot BJ, Aouizerat BE, Miaskowski C (2014) Cytokine candidate genes predict the development of secondary lymphedema following breast cancer surgery. Lymphat Res Biol 12(1):10–22

    Article  CAS  Google Scholar 

  31. Smoot B, Kober KM, Paul SM, Levine JD, Abrams G, Mastick J, Topp K, Conley YP, Miaskowski CA (2017) Potassium channel candidate genes predict the development of secondary lymphedema following breast cancer surgery. Nurs Res 66(2):85–94

    Article  Google Scholar 

  32. Visser J, van Geel M, Cornelissen AJM, van der Hulst RRWJ, Qiu SS (2019) Breast cancer-related lymphedema and genetic predisposition: a systematic review of the literature. Lymphat Res Biol (online). https://doi.org/10.1089/lrb.2017.0083

    Article  Google Scholar 

  33. Boccardo F, Casabona F, De Cian F, Friedman D, Villa G, Bogliolo S, Ferrero S, Murelli F, Campisi C (2009) Lymphedema microsurgical preventive healing approach: a new technique for primary prevention of arm lymphedema after mastectomy. Ann Surg Oncol 16:703–708

    Article  Google Scholar 

  34. Box RC, Reul-Hirche HM, Bullock-Saxton JE, Furnival CM (2002) Physiotherapy after breast cancer surgery: results of a randomized controlled study to minimise lymphedema. Breast Cancer Res Treat 75:51–64

    Article  Google Scholar 

  35. Kilgore LJ, Korentager SS, Hangge AN, Amin AL, Balanoff CR, Larson KE, Mitchell MP, Chen JG, Burgen E, Khan QJ, O’Dea AP, Nye L, Sharma P, Wagner JL (2018) Reducing breast cancer-related lymphedema (BCRL) through prospective surveillance monitoring using bioimpedance spectroscopy (BIS) and patient directed self-interventions. Ann Surg Oncol 25(10):2948–2952. https://doi.org/10.1245/s10434-018-6601-8

    Article  PubMed  Google Scholar 

  36. Koelmeyer LA, Borotkanics RJ, Alcorso J, Prah P, Winch CJ, Nakhel K, Dean CM, Boyages J (2019) Early surveillance is associated with less incidence and severity of breast cancer-related lymphedema compared with a traditional referral model of care. Cancer 125(6):854–862. https://doi.org/10.1002/cncr.31873

    Article  PubMed  Google Scholar 

  37. Armer JM, Hulett JM, Bernas M, Ostby P, Stewart BR, Cormier JN (2013) Best practice guidelines in assessment, risk reduction, management, and surveillance for post-breast cancer lymphedema. Curr Breast Cancer Rep 5(2):134–144

    Article  Google Scholar 

  38. Kaufman DI, Shah C, Vicini FA, Rizzi M (2017) Utilization of bioimpedance spectroscopy in the prevention of chronic breast cancer-related lymphedema. Breast Can Res Treat 166:809–815. https://doi.org/10.1007/s10549-017-4451-x

    Article  CAS  Google Scholar 

  39. Whitworth PW, Cooper A (2017) Reducing chronic breast cancer-related lymphedema utilizing a program of prospective surveillance with bioimpedance spectroscopy. Breast J 24(1):62–65. https://doi.org/10.1111/tbj.12939

    Article  CAS  PubMed  Google Scholar 

  40. Soran A, Ozmen T, McGuire KP, Diego EJ, McAuliffe PF, Bonaventura M, Ahrendt GM, DeGore L, Johnson R (2014) The importance of detection of subclinical lymphedema for the prevention of breast cancer-related clinical lymphedema after axillary lymph node dissection: a prospective observational study. Lymph Res Bio 12(4):289–294

    Article  Google Scholar 

  41. Ridner SH, Dietrich MS, Cowher MS, Taback B, McLaughlin S, Ajkay N, Boyages J, Koelmeyer L, DeSnyder SM, Wagner J, Abramson V, Moore A, Shah C (2019) A randomized trial evaluating bioimpedance spectroscopy versus tape measurement for the prevention of lymphedema following treatment for breast cancer: interim analysis. Ann Surg Oncol 26(10):3250–3259. https://doi.org/10.1245/s10434-019-07344-5

    Article  PubMed  PubMed Central  Google Scholar 

  42. Lasinski BB, McKillip Thrift K, Squire D, Austin MK, Smith KM, Wanchai A, Green JM, Stewart BR, Cormier JN, Armer JM (2012) A systematic review of the evidence for complete decongestive therapy in the treatment of lymphedema from 2004 to 2011. PM&R 4(8):580–601

    Article  Google Scholar 

  43. Fu MR, Deng J, Armer JM (2014) Putting evidence into practice: cancer-related lymphedema. Clin J Oncol Nurs 18(Suppl):68–79

    Article  Google Scholar 

  44. Tam K, Shen L, Munneke JR, Ackerson LM, Partee PN, Somkin CP, Andre M, Kutner SE, Thiadens SRJ, Kwan ML (2012) Clinician awareness and knowledge of BCRL in a large, integrated healthcare delivery setting. Breast Cancer Res Treat 131(3):1029–1038

    Article  Google Scholar 

  45. Lighthouse Lymphedema Network; Shedding Light on Lymphedema. https://lighthouselymphedema.org/home2/. Assessed on 10 March 2021

  46. National Lymphedema Network (NLN). https://www.lymphnet.org. Assessed on 10 March 2021

  47. American Lymphedema Framework Project (ALFP). https://www.alfp.org/. Assessed on 10 March 2021

  48. Granzow JW (2018) Lymphedema surgery: the current state of the art. Clin Exp Metastasis 35(5–6):553–558. https://doi.org/10.1007/s10585-018-9897-7

    Article  PubMed  Google Scholar 

  49. Suami H, Chang DW (2010) Overview of surgical treatments for breast cancer-related lymphedema. Plast Reconstr Surg 126(6):1853–1863

    Article  CAS  Google Scholar 

  50. Granzow JW, Soderberg JM, Kaji AH, Dauphine C (2014) Review of current surgical treatments for lymphedema. Ann Surg Oncol Ann Surg Oncol 21(4):1195–1201

    Article  Google Scholar 

  51. Masia J, Pons G, Nardulli ML (2015) Combined surgical treatment in breast cancer-related lymphedema. J Reconstr Microsurg 32:16–27

    Article  Google Scholar 

  52. Boccardo F, De Cian F, Campisi CC, Molinari L, Spinaci S, Dessalvi S, Talamo G, Campisi C, Villa G, Bellini C, Parodi A, Santi PL, Campisi C (2013) Surgical prevention and treatment of lymphedema after lymph node dissection in patients with cutaneous melanoma. Lymphology 46(1):20–26

    CAS  PubMed  Google Scholar 

  53. Boccardo F, Valenzano M, Costantini S, Casabona F, Morotti M, Sala P, De Cian F, Molinari L, Spinaci S, Dessalvi S, Campisi CC, Villa G, Campisi C (2016) LYMPHA technique to prevent secondary lower limb lymphedema. Ann Surg Oncol 23(11):3558–3563. https://doi.org/10.1245/s10434-016-5282-4

    Article  PubMed  Google Scholar 

  54. Granzow JW, Soderberg JM, Dauphine C (2014) A novel two-stage surgical approach to treat chronic lymphedema. Breast J 20(4):420–422. https://doi.org/10.1111/tbj.12282

    Article  PubMed  Google Scholar 

  55. Granzow JW, Soderberg JM, Kaji AH, Dauphine C (2014) An effective system of surgical treatment of lymphedema. Ann Surg Oncol 21(4):1189–1194

    Article  Google Scholar 

  56. Brorson H, Svensson H, Norrgren K, Thorsson O (1998) Liposuction reduces arm lymphedema without significantly altering the already impaired lymph transport. Lymphology 31:156–172

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. TCU and UNTHSC School of Medicine, Fort Worth, TX, USA

    Michael Bernas

  2. California Pacific Medical Center Cancer Center, CPMC, San Francisco, CA, USA

    Saskia R. J. Thiadens

  3. Parkridge Medical Center Rehabilitation, Chattanooga, TN, USA

    Paula Stewart

  4. Division of Plastic Surgery, UCLA David Geffen School of Medicine, Los Angeles, CA, USA

    Jay Granzow

  5. Harbor-UCLA Medical Center, Los Angeles, CA, USA

    Jay Granzow

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  1. Michael Bernas
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  2. Saskia R. J. Thiadens
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  3. Paula Stewart
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  4. Jay Granzow
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Correspondence to Michael Bernas.

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Bernas, M., Thiadens, S.R.J., Stewart, P. et al. Secondary lymphedema from cancer therapy. Clin Exp Metastasis 39, 239–247 (2022). https://doi.org/10.1007/s10585-021-10096-w

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