Skip to main content
Top
Published in: BMC Cancer 1/2019

Open Access 01-12-2019 | Cytostatic Therapy | Research article

It’s never too late - balance and endurance training improves functional performance, quality of life, and alleviates neuropathic symptoms in cancer survivors suffering from chemotherapy-induced peripheral neuropathy: results of a randomized controlled trial

Authors: S. Kneis, A. Wehrle, J. Müller, C. Maurer, G. Ihorst, A. Gollhofer, H. Bertz

Published in: BMC Cancer | Issue 1/2019

Login to get access

Abstract

Background

Chemotherapy-induced peripheral neuropathy (CIPN) can affect functional performance and quality of life considerably. Since balance training has proven to enhance physical function, it might be a promising strategy to manage CIPN-induced functional impairments.

Methods

Fifty cancer survivors with persisting CIPN after finishing their treatment were randomly allocated to an intervention (IG) or active control group (CG). The IG did endurance plus balance training, the CG only endurance training (twice weekly over 12 weeks). Pre- and post-assessments included functional performance, cardiorespiratory fitness, vibration sense, and self-reported CIPN symptoms (EORTC QLQ-CIPN20).

Results

Intention-to-treat analyses (n = 41) did not reveal a significant group difference (CG minus IG) for sway path in semi-tandem stance after intervention (primary endpoint), adjusted for baseline. However, our per-protocol analysis of 37 patients with training compliance ≥70% revealed: the IG reduced their sway path during semi-tandem stance (− 76 mm, 95% CI -141 – -17; CG: -6 mm, 95% CI -52 – 50), improved the duration standing on one leg on instable surface (11 s, 95% CI 8–17; CG: 0 s, 95%CI 0–5) and reported decreased motor symptoms (−8points, 95% CI -18 – 0; CG: -2points 95% CI -6 – 2). Both groups reported reduced overall- (IG: -10points, 95% CI -17 – -4; CG: -6points, 95% CI -11 – -1) and sensory symptoms (IG: -7points, 95% CI -15 – 0; CG: -7points, 95% CI -15 – 0), while only the CG exhibited objectively better vibration sense (knuckle: 0.8points, 95% CI 0.3–1.3; IG: 0.0points, 95% CI -1.1 – 0.9; patella: 1.0points, 95% CI 0.4–1.6: IG: -0.8points, 95% CI -0.2 – 0.0). Furthermore, maximum power output during cardiopulmonary exercise test increased in both groups (IG and CG: 0.1 W/kg, 95% CI 0.0–0.2), but only the CG improved their jump height (2 cm, 95% CI 0.5–3.5; IG: 1 cm, 95% CI -0.4 – 3.2).

Conclusion

We suppose that endurance training induced a reduction in sensory symptoms in both groups, while balance training additionally improved patients’ functional status. This additional functional effect might reflect the IG’s superiority in the CIPN20 motor score. Both exercises provide a clear and relevant benefit for patients with CIPN.

Trial registration

German Clinical Trials Register (DRKS) number: DRKS00005419, prospectively registered on November 19, 2013.
Literature
1.
go back to reference Mols F, Beijers T, Vreugdenhil G. Van de poll-Franse L. chemotherapy-induced peripheral neuropathy and its association with quality of life: a systematic review. Support Care Cancer. 2014;22(8):2261–9.CrossRef Mols F, Beijers T, Vreugdenhil G. Van de poll-Franse L. chemotherapy-induced peripheral neuropathy and its association with quality of life: a systematic review. Support Care Cancer. 2014;22(8):2261–9.CrossRef
2.
go back to reference Seretny M, Currie GL, Sena ES, Ramnarine S, Grant R, MacLeod MR, et al. Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: a systematic review and meta-analysis. Pain. 2014;155(12):2461–70.CrossRef Seretny M, Currie GL, Sena ES, Ramnarine S, Grant R, MacLeod MR, et al. Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: a systematic review and meta-analysis. Pain. 2014;155(12):2461–70.CrossRef
3.
go back to reference Pike CT, Birnbaum HG, Muehlenbein CE, Pohl GM, Natale RB. Healthcare costs and workloss burden of patients with chemotherapy-associated peripheral neuropathy in breast, ovarian, head and neck, and nonsmall cell lung cancer. Chemother Res Pract. 2012;2012:913848.PubMedPubMedCentral Pike CT, Birnbaum HG, Muehlenbein CE, Pohl GM, Natale RB. Healthcare costs and workloss burden of patients with chemotherapy-associated peripheral neuropathy in breast, ovarian, head and neck, and nonsmall cell lung cancer. Chemother Res Pract. 2012;2012:913848.PubMedPubMedCentral
4.
go back to reference Winters-Stone KM, Horak F, Jacobs PG, Trubowitz P, Dieckmann NF, Stoyles S, et al. Falls, functioning, and disability among women with persistent symptoms of chemotherapy-induced peripheral neuropathy. J Clin Oncol. 2017;35(23):2604–12.CrossRef Winters-Stone KM, Horak F, Jacobs PG, Trubowitz P, Dieckmann NF, Stoyles S, et al. Falls, functioning, and disability among women with persistent symptoms of chemotherapy-induced peripheral neuropathy. J Clin Oncol. 2017;35(23):2604–12.CrossRef
5.
go back to reference van Schie CHM. Neuropathy: mobility and quality of life. Diabetes Metab Res Rev. 2008;24(Suppl 1):45–51.CrossRef van Schie CHM. Neuropathy: mobility and quality of life. Diabetes Metab Res Rev. 2008;24(Suppl 1):45–51.CrossRef
6.
go back to reference Brown JC, Harhay MO, Harhay MN. Physical function as a prognostic biomarker among cancer survivors. Br J Cancer. 2015;112:194–8.CrossRef Brown JC, Harhay MO, Harhay MN. Physical function as a prognostic biomarker among cancer survivors. Br J Cancer. 2015;112:194–8.CrossRef
7.
go back to reference Hershman DL, Lacchetti C, Dworkin RH, Smith EML, Bleeker J, Cavaletti G, et al. Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2014;32(18):1941–67.CrossRef Hershman DL, Lacchetti C, Dworkin RH, Smith EML, Bleeker J, Cavaletti G, et al. Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2014;32(18):1941–67.CrossRef
8.
go back to reference Streckmann F, Zopf EM, Lehmann HC, May K, Rizza J, Zimmer P, et al. Exercise intervention studies in patients with peripheral neuropathy: a systematic review. Sports Med Auckl NZ. 2014;44(9):1289–304.CrossRef Streckmann F, Zopf EM, Lehmann HC, May K, Rizza J, Zimmer P, et al. Exercise intervention studies in patients with peripheral neuropathy: a systematic review. Sports Med Auckl NZ. 2014;44(9):1289–304.CrossRef
9.
go back to reference Balducci S, Iacobellis G, Parisi L, Di Biase N, Calandriello E, Leonetti F, et al. Exercise training can modify the natural history of diabetic peripheral neuropathy. J Diabetes Complicat. 2006;20(4):216–23.CrossRef Balducci S, Iacobellis G, Parisi L, Di Biase N, Calandriello E, Leonetti F, et al. Exercise training can modify the natural history of diabetic peripheral neuropathy. J Diabetes Complicat. 2006;20(4):216–23.CrossRef
10.
go back to reference Dixit S, Maiya AG, Shastry BA. Effect of aerobic exercise on peripheral nerve functions of population with diabetic peripheral neuropathy in type 2 diabetes: a single blind, parallel group randomized controlled trial. J Diabetes Complicat. 2014;28(3):332–9.CrossRef Dixit S, Maiya AG, Shastry BA. Effect of aerobic exercise on peripheral nerve functions of population with diabetic peripheral neuropathy in type 2 diabetes: a single blind, parallel group randomized controlled trial. J Diabetes Complicat. 2014;28(3):332–9.CrossRef
11.
go back to reference Song CH, Petrofsky JS, Lee SW, Lee KJ, Yim JE. Effects of an exercise program on balance and trunk proprioception in older adults with diabetic neuropathies. Diabetes Technol Ther. 2011;13(8):803–11.CrossRef Song CH, Petrofsky JS, Lee SW, Lee KJ, Yim JE. Effects of an exercise program on balance and trunk proprioception in older adults with diabetic neuropathies. Diabetes Technol Ther. 2011;13(8):803–11.CrossRef
12.
go back to reference Richardson J, Sandman D, Vela S. A focused exercise regimen improves clinical measures of balance in patients with peripheral neuropathy. Arch Phys Med Rehabil. 2001;82(2):205–9.CrossRef Richardson J, Sandman D, Vela S. A focused exercise regimen improves clinical measures of balance in patients with peripheral neuropathy. Arch Phys Med Rehabil. 2001;82(2):205–9.CrossRef
13.
go back to reference Allet L, Armand S, de Bie RA, Golay A, Monnin D, Aminian K, et al. The gait and balance of patients with diabetes can be improved: a randomised controlled trial. Diabetologia. 2010;53(3):458–66.CrossRef Allet L, Armand S, de Bie RA, Golay A, Monnin D, Aminian K, et al. The gait and balance of patients with diabetes can be improved: a randomised controlled trial. Diabetologia. 2010;53(3):458–66.CrossRef
14.
go back to reference Sartor CD, Watari R, Pássaro AC, Picon AP, Hasue RH, Sacco IC. Effects of a combined strengthening, stretching and functional training program versus usual-care on gait biomechanics and foot function for diabetic neuropathy: a randomized controlled trial. BMC Musculoskelet Disord. 2012;13:36.CrossRef Sartor CD, Watari R, Pássaro AC, Picon AP, Hasue RH, Sacco IC. Effects of a combined strengthening, stretching and functional training program versus usual-care on gait biomechanics and foot function for diabetic neuropathy: a randomized controlled trial. BMC Musculoskelet Disord. 2012;13:36.CrossRef
15.
go back to reference Taube W, Gruber M, Gollhofer A. Spinal and supraspinal adaptations associated with balance training and their functional relevance. Acta Physiol (Oxf). 2008;193(2):101–16.CrossRef Taube W, Gruber M, Gollhofer A. Spinal and supraspinal adaptations associated with balance training and their functional relevance. Acta Physiol (Oxf). 2008;193(2):101–16.CrossRef
16.
go back to reference Zech A, Hübscher M, Vogt L, Banzer W, Hänsel F, Pfeifer K. Balance training for neuromuscular control and performance enhancement: a systematic review. J Athl Train. 2010;45(4):392–403.CrossRef Zech A, Hübscher M, Vogt L, Banzer W, Hänsel F, Pfeifer K. Balance training for neuromuscular control and performance enhancement: a systematic review. J Athl Train. 2010;45(4):392–403.CrossRef
17.
go back to reference Duregon F, Vendramin B, Bullo V, Gobbo S, Cugusi L, Di Blasio A, et al. Effects of exercise on cancer patients suffering chemotherapy-induced peripheral neuropathy undergoing treatment: a systematic review. Crit Rev Oncol Hematol. 2018;121:90–100.CrossRef Duregon F, Vendramin B, Bullo V, Gobbo S, Cugusi L, Di Blasio A, et al. Effects of exercise on cancer patients suffering chemotherapy-induced peripheral neuropathy undergoing treatment: a systematic review. Crit Rev Oncol Hematol. 2018;121:90–100.CrossRef
18.
go back to reference Streckmann F, Kneis S, Leifert JA, Baumann FT, Kleber M, Ihorst G, et al. Exercise program improves therapy-related side-effects and quality of life in lymphoma patients undergoing therapy. Ann Oncol. 2014;25(2):493–9.CrossRef Streckmann F, Kneis S, Leifert JA, Baumann FT, Kleber M, Ihorst G, et al. Exercise program improves therapy-related side-effects and quality of life in lymphoma patients undergoing therapy. Ann Oncol. 2014;25(2):493–9.CrossRef
19.
go back to reference Granacher U, Muehlbauer T, Taube W, Gollhofer A, Gruber M. Sensorimotor Training. In: Cardinale M, Newton R, Nosaka K, editors. Strength and conditioning: biological principles and practical applications. San Francisco: Wiley-Blackwell; 2011. p. 399. Granacher U, Muehlbauer T, Taube W, Gollhofer A, Gruber M. Sensorimotor Training. In: Cardinale M, Newton R, Nosaka K, editors. Strength and conditioning: biological principles and practical applications. San Francisco: Wiley-Blackwell; 2011. p. 399.
20.
go back to reference Borg G. Psychophysical bases of perceived exertion. Med Sci Sports Exerc. 1982;14(5):377–81.CrossRef Borg G. Psychophysical bases of perceived exertion. Med Sci Sports Exerc. 1982;14(5):377–81.CrossRef
21.
go back to reference Scharhag-Rosenberger F, Becker T, Streckmann F, Schmidt K, Berling A, Bernardi A, et al. Studien zu körperlichem Training bei onkologischen Patienten: Empfehlungen zu den Erhebungsmethoden. Dtsch Z Für Sportmed. 2014;65(11):304–13.CrossRef Scharhag-Rosenberger F, Becker T, Streckmann F, Schmidt K, Berling A, Bernardi A, et al. Studien zu körperlichem Training bei onkologischen Patienten: Empfehlungen zu den Erhebungsmethoden. Dtsch Z Für Sportmed. 2014;65(11):304–13.CrossRef
22.
go back to reference Pestronk A, Florence J, Levine T, Al-Lozi MT, Lopate G, Miller T, et al. Sensory exam with a quantitative tuning fork: rapid, sensitive and predictive of SNAP amplitude. Neurology. 2004;62(3):461–4.CrossRef Pestronk A, Florence J, Levine T, Al-Lozi MT, Lopate G, Miller T, et al. Sensory exam with a quantitative tuning fork: rapid, sensitive and predictive of SNAP amplitude. Neurology. 2004;62(3):461–4.CrossRef
23.
go back to reference Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85(5):365–76.CrossRef Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85(5):365–76.CrossRef
24.
go back to reference Wasserman. Principles of Exercise Testing & Interpretation: including pathophysiology and clinical applications, vol. 586. Philadelphia: Lippincott Williams & Wilkins; 1999. Wasserman. Principles of Exercise Testing & Interpretation: including pathophysiology and clinical applications, vol. 586. Philadelphia: Lippincott Williams & Wilkins; 1999.
25.
go back to reference Fritz CO, Morris PE, Richler JJ. Effect size estimates: current use, calculations, and interpretation. J Exp Psychol Gen. 2012;141(1):2–18.CrossRef Fritz CO, Morris PE, Richler JJ. Effect size estimates: current use, calculations, and interpretation. J Exp Psychol Gen. 2012;141(1):2–18.CrossRef
26.
go back to reference Wampler MA, Topp KS, Miaskowski C, Byl NN, Rugo HS, Hamel K. Quantitative and clinical description of postural instability in women with breast Cancer treated with Taxane chemotherapy. Arch Phys Med Rehabil. 2007;88(8):1002–8.CrossRef Wampler MA, Topp KS, Miaskowski C, Byl NN, Rugo HS, Hamel K. Quantitative and clinical description of postural instability in women with breast Cancer treated with Taxane chemotherapy. Arch Phys Med Rehabil. 2007;88(8):1002–8.CrossRef
27.
go back to reference Tofthagen C, Overcash J, Kip K. Falls in persons with chemotherapy-induced peripheral neuropathy. Support Care Cancer. 2012;20(3):583–9.CrossRef Tofthagen C, Overcash J, Kip K. Falls in persons with chemotherapy-induced peripheral neuropathy. Support Care Cancer. 2012;20(3):583–9.CrossRef
28.
go back to reference Kneis S, Wehrle A, Freyler K, Lehmann K, Rudolphi B, Hildenbrand B, et al. Balance impairments and neuromuscular changes in breast cancer patients with chemotherapy-induced peripheral neuropathy. Clin Neurophysiol. 2016;127(2):1481–90.CrossRef Kneis S, Wehrle A, Freyler K, Lehmann K, Rudolphi B, Hildenbrand B, et al. Balance impairments and neuromuscular changes in breast cancer patients with chemotherapy-induced peripheral neuropathy. Clin Neurophysiol. 2016;127(2):1481–90.CrossRef
29.
go back to reference Herman HK, Monfort SM, Pan XJ, Chaudhari AMW, Lustberg MB. Effect of chemotherapy-induced peripheral neuropathy on postural control in cancer survivors. J Clin Oncol. 2017;35(Suppl 5):128.CrossRef Herman HK, Monfort SM, Pan XJ, Chaudhari AMW, Lustberg MB. Effect of chemotherapy-induced peripheral neuropathy on postural control in cancer survivors. J Clin Oncol. 2017;35(Suppl 5):128.CrossRef
30.
go back to reference Marshall TF, Zipp GP, Battaglia F, Moss R, Bryan S. Chemotherapy-induced-peripheral neuropathy, gait and fall risk in older adults following cancer treatment. J Cancer Res Pract. 2017;4(4):134–8.CrossRef Marshall TF, Zipp GP, Battaglia F, Moss R, Bryan S. Chemotherapy-induced-peripheral neuropathy, gait and fall risk in older adults following cancer treatment. J Cancer Res Pract. 2017;4(4):134–8.CrossRef
31.
go back to reference Monfort SM, Pan X, Patrick R, Ramaswamy B, Wesolowski R, Naughton MJ, et al. Gait, balance, and patient-reported outcomes during taxane-based chemotherapy in early-stage breast cancer patients. Breast Cancer Res Treat. 2017;164(1):69–77.CrossRef Monfort SM, Pan X, Patrick R, Ramaswamy B, Wesolowski R, Naughton MJ, et al. Gait, balance, and patient-reported outcomes during taxane-based chemotherapy in early-stage breast cancer patients. Breast Cancer Res Treat. 2017;164(1):69–77.CrossRef
32.
go back to reference Schwenk M, Grewal GS, Holloway D, Muchna A, Garland L, Najafi B. Interactive sensor-based balance Training in older Cancer patients with chemotherapy-induced peripheral neuropathy: a randomized controlled trial. Gerontology. 2016;62(5):553–63.CrossRef Schwenk M, Grewal GS, Holloway D, Muchna A, Garland L, Najafi B. Interactive sensor-based balance Training in older Cancer patients with chemotherapy-induced peripheral neuropathy: a randomized controlled trial. Gerontology. 2016;62(5):553–63.CrossRef
33.
go back to reference Zimmer P, Trebing S, Timmers-Trebing U, Schenk A, Paust R, Bloch W, et al. Eight-week, multimodal exercise counteracts a progress of chemotherapy-induced peripheral neuropathy and improves balance and strength in metastasized colorectal cancer patients: a randomized controlled trial. Support Care Cancer. 2017;26(2):615–24.CrossRef Zimmer P, Trebing S, Timmers-Trebing U, Schenk A, Paust R, Bloch W, et al. Eight-week, multimodal exercise counteracts a progress of chemotherapy-induced peripheral neuropathy and improves balance and strength in metastasized colorectal cancer patients: a randomized controlled trial. Support Care Cancer. 2017;26(2):615–24.CrossRef
34.
go back to reference Streckmann F, Lehmann HC, Balke M, Schenk A, Oberste M, Heller A, et al. Sensorimotor training and whole-body vibration training have the potential to reduce motor and sensory symptoms of chemotherapy-induced peripheral neuropathy-a randomized controlled pilot trial. Support Care Cancer. 2018. [Epub ahead of print]. Streckmann F, Lehmann HC, Balke M, Schenk A, Oberste M, Heller A, et al. Sensorimotor training and whole-body vibration training have the potential to reduce motor and sensory symptoms of chemotherapy-induced peripheral neuropathy-a randomized controlled pilot trial. Support Care Cancer. 2018. [Epub ahead of print].
35.
go back to reference Vandervoort AA. Aging of the human neuromuscular system. Muscle Nerve. 2002;25(1):17–25.CrossRef Vandervoort AA. Aging of the human neuromuscular system. Muscle Nerve. 2002;25(1):17–25.CrossRef
36.
go back to reference van der Kooij H, Peterka RJ. Non-linear stimulus-response behavior of the human stance control system is predicted by optimization of a system with sensory and motor noise. J Comput Neurosci. 2011;30(3):759–78.CrossRef van der Kooij H, Peterka RJ. Non-linear stimulus-response behavior of the human stance control system is predicted by optimization of a system with sensory and motor noise. J Comput Neurosci. 2011;30(3):759–78.CrossRef
37.
go back to reference Fukuda Y, Li Y, Segal RA. A mechanistic understanding of axon degeneration in chemotherapy-induced peripheral neuropathy. Front Neurosci. 2017;11:481.CrossRef Fukuda Y, Li Y, Segal RA. A mechanistic understanding of axon degeneration in chemotherapy-induced peripheral neuropathy. Front Neurosci. 2017;11:481.CrossRef
38.
go back to reference Han Y, Smith MT. Pathobiology of cancer chemotherapy-induced peripheral neuropathy (CIPN). Front Pharmacol. 2013;4:156.CrossRef Han Y, Smith MT. Pathobiology of cancer chemotherapy-induced peripheral neuropathy (CIPN). Front Pharmacol. 2013;4:156.CrossRef
39.
go back to reference Kieffer JM, Postma TJ, Van de Poll-Franse L, Mols F, Heimans JJ, Cavaletti G, et al. Evaluation of the psychometric properties of the EORTC chemotherapy-induced peripheral neuropathy questionnaire (QLQ-CIPN20). Qual Life Res. 2017;26(11):2999–3010.CrossRef Kieffer JM, Postma TJ, Van de Poll-Franse L, Mols F, Heimans JJ, Cavaletti G, et al. Evaluation of the psychometric properties of the EORTC chemotherapy-induced peripheral neuropathy questionnaire (QLQ-CIPN20). Qual Life Res. 2017;26(11):2999–3010.CrossRef
40.
go back to reference Park J-S, Höke A. Treadmill exercise induced functional recovery after peripheral nerve repair is associated with increased levels of neurotrophic factors. PLoS One. 2014;9(3):e90245.CrossRef Park J-S, Höke A. Treadmill exercise induced functional recovery after peripheral nerve repair is associated with increased levels of neurotrophic factors. PLoS One. 2014;9(3):e90245.CrossRef
41.
go back to reference Cooper MA, Kluding PM, Wright DE. Emerging relationships between exercise, sensory nerves, and neuropathic pain. Front Neurosci. 2016;10:372.CrossRef Cooper MA, Kluding PM, Wright DE. Emerging relationships between exercise, sensory nerves, and neuropathic pain. Front Neurosci. 2016;10:372.CrossRef
42.
go back to reference Beijersbergen CMI, Granacher U, Gäbler M, DeVita P, Hortobágyi T. Power training-induced increases in muscle activation during gait in old adults. Med Sci Sports Exerc. 2017;49(11):2198–205.CrossRef Beijersbergen CMI, Granacher U, Gäbler M, DeVita P, Hortobágyi T. Power training-induced increases in muscle activation during gait in old adults. Med Sci Sports Exerc. 2017;49(11):2198–205.CrossRef
Metadata
Title
It’s never too late - balance and endurance training improves functional performance, quality of life, and alleviates neuropathic symptoms in cancer survivors suffering from chemotherapy-induced peripheral neuropathy: results of a randomized controlled trial
Authors
S. Kneis
A. Wehrle
J. Müller
C. Maurer
G. Ihorst
A. Gollhofer
H. Bertz
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2019
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-019-5522-7

Other articles of this Issue 1/2019

BMC Cancer 1/2019 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine