Skip to main content
SpringerLink
Log in

Adjuvant Radiotherapy

  • Chapter
  • First Online:
Management of Breast Cancer in Older Women

Abstract

There is a dearth of level 1 (randomised controlled trial) evidence on adjuvant radiotherapy confined to older patients but it is slowly accumulating and influencing guidelines and practice. There are wide international variations in the application of adjuvant radiotherapy after breast conserving surgery and mastectomy in this age group. There are conflicting data on the effect of age on risk of local recurrence. Local recurrence rates have been falling in older patients treated by breast conserving therapy, reflecting the impact of screening, closer attention to surgical margins, better systemic therapy and radiotherapy. Recent trials support the use of hypofractionation and selected forms of partial breast irradiation. Breast boost is recommended in higher risk patients after breast conserving surgery. There is growing support for selective omission of postoperative radiotherapy in ‘low risk’ older patients. Trials of biomarker- assisted selection of such subgroups are ongoing. There is no level 1 evidence on postmastectomy radiotherapy (PMRT) confined to older patients. PMRT remains standard for patients with 4 or more positive nodes. For patients with 1–3 involved nodes, the role of PMRT remains controversial.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Biganzoli L, Wildiers H, Oakman C, et al. Management of elderly patients with breast cancer: updated recommendations of the International Society of Geriatric Oncology (SIOG), and European Society of Breast Cancer Specialists (EUSOMA). Lancet Oncol. 2012;13:e148–60.

    Article  PubMed  Google Scholar 

  2. Ballard-Barbash R, Potosky AL, Harlan LC, et al. Factors associated with surgical and radiation therapy for early stage breast cancer in older women. J Natl Cancer Inst. 1996;88:717–26.

    Article  Google Scholar 

  3. Kiderlen M, Bastiaannet E, Walsh PM, et al. Surgical treatment of early breast cancer in elderly: an international comparison. Breast Cancer Res Treat. 2012;132:675–82.

    Article  CAS  PubMed  Google Scholar 

  4. Moran MS, Schnitt SJ, Giuliano AE, et al. Society of Surgical Oncology-American Society for Radiation Oncology consensus guidelines on margins for breast-conserving surgery with whole-breast irradiation in stages 1 and 11 invasive breast cancer. Int J Rad Oncol Biol Phys. 2014;88:553–64.

    Article  Google Scholar 

  5. Mamtani M, Gonzalez JJ, Neo D, et al. Early-stage breast cancer in the octogenarian: tumor characteristics, treatment choices, and clinical outcomes. Ann Surg Oncol. 2016;23:3371–8.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Scalliet PGM. Adjuvant radiotherapy. In: Reed MW, Audisio RA, editors. Management of breast cancer in older women. London: Springer-Verlag; 2010. https://doi.org/10.1007/978-1-84800-255-4_17.

    Chapter  Google Scholar 

  7. Hughes KS, Schnaper LA. Can older women with early breast cancer avoid radiation? Lancet Oncol. 2015;16:235–7.

    Article  PubMed  Google Scholar 

  8. Courdi A, Gerard JP. Radiotherapy for elderly patients with breast cancer. J Clin Oncol. 2013;31:4571.

    Article  PubMed  Google Scholar 

  9. Darby SC, Ewertz M, Hall P, et al. Ischaemic heart disease after breast cancer radiotherapy. N Engl J Med. 2013;368:2527.

    Article  CAS  PubMed  Google Scholar 

  10. Grantzau T, Overgaard J. Risk of second non-breast cancer deaths among patients treated with and without postoperative radiotherapy for primary breast cancer: a systematic review and meta-analysis of population-based studies including 522,739 patients. Radiother Oncol. 2016;121:402–13.

    Article  PubMed  Google Scholar 

  11. Taylor C, Correa C, Duane FK, et al.; for the Early Breast Cancer Trialists’ Collaborative Group. Estimating the risks of breast cancer radiotherapy: evidence from modern radiation doses to the lungs and heart and from previous randomized trials. J Clin Oncol. 2017;35:1641–9.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Veronesi U, Luini A, Del Vecchio M, et al. Radiotherapy after breast-conserving surgery in women with localized breast cancer. N Engl J Med. 1993;328:1587–91.

    Article  CAS  PubMed  Google Scholar 

  13. Fisher B, Anderson S, Redmond CK, et al. Reanalysis and results after 12 years of follow-up in a randomized trial comparing mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med. 1995;333:1456–61.

    Article  CAS  PubMed  Google Scholar 

  14. Forrest AP, Stewart HJ, Everington D, et al.; on behalf of Scottish Cancer Trials Breast Group. Randomised controlled trial of conservation therapy for breast cancer: 6-year analysis of the Scottish trial. Lancet. 1996;348:708–13.

    Google Scholar 

  15. Van der Leij F, van Werkhoven E, Bosma S, et al. Low risk of recurrence in elderly patients treated with breast conserving therapy in a single institute. Breast. 2016;30:19–25.

    Article  PubMed  Google Scholar 

  16. Mannino M, Yarnold JR. Local relapse rates are falling after breast conserving surgery and systemic therapy for early breast cancer: can radiotherapy ever safely be withheld? Radiother Oncol. 2009;90(1):14–22.

    Article  PubMed  Google Scholar 

  17. Speers C, Zhao S, Liu M, Bartelink H, Pierce LJ, Feng FY. Development and validation of a novel radiosensitivity signature in human breast cancer. Clin Cancer Res. 2015;21(16):3667–77.

    Article  CAS  PubMed  Google Scholar 

  18. Cuzick J, Stewart J, Rutqvist L, et al. Cause-specific mortality in long-term survivors of breast cancer who participated in trials of radiotherapy. J Clin Oncol. 1994;12:447–53.

    Article  CAS  PubMed  Google Scholar 

  19. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials. Lancet. 2000;355:1757–70.

    Article  Google Scholar 

  20. Overgaard M, Hansen PS, Overgaard J, et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. N Engl J Med. 1997;337:949–55.

    Article  CAS  PubMed  Google Scholar 

  21. Ragaz J, Jackson SM, Le N, Plenderleith IH, Spinelli JJ, Basco VE, Wilson KS, Knowling MA, Coppin CM, Paradis M, Coldman AJ, Olivotto IA. Adjuvant radiotherapy and chemotherapy in node-positive premenopausal women with breast cancer. N Engl J Med. 1997;337(14):956–62.

    Article  CAS  PubMed  Google Scholar 

  22. Overgaard M, Jensen M-B, Overgaard J, et al. Postoperative radiotherapy in high-risk postmenopausal breast cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG82c randomized trial. Lancet. 1999;353:1641–8. Adjuvant radiotherapy and chemotherapy in node-positive postmenopausal women with breast cancer. N Engl J Med 1997;337:956–962.

    Article  CAS  PubMed  Google Scholar 

  23. Hojris D, Overgaard M, Christensenn JJ, Radiotherapy Committee of the Danish Cancer Cooperative Group, et al. Morbidity and mortality of ischaemic heart disease in high-risk breast-cancer patients after adjuvant postmastectomy systemic treatment with or without radiotherapy: analysis of DBCG 82b and 82c trials. Lancet. 1999;354:1425–30.

    Article  CAS  PubMed  Google Scholar 

  24. Karnofsky HS, Lecture M. Natural history of small breast cancers. J Clin Oncol. 1994;12:2229–34.

    Article  Google Scholar 

  25. Harris JR. Fifty years of progress in radiation therapy for breast cancer. Am Soc Clin Oncol Educ Book. 2014:21–5.

    Article  Google Scholar 

  26. Jatoi I, Benson J, Kunkler IH. Hypothesis: can the abcopal effect explain the impact of adjuvant radiotherapy on breast cancer mortality? NPJ Breast Cancer. 2018;4:8.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, et al. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011;378:1707–16.

    Article  CAS  PubMed  Google Scholar 

  28. Hughes KS, Schnaper LA, Berry D, et al. Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. N Engl J Med. 2004;351:971–7.

    Article  CAS  PubMed  Google Scholar 

  29. Hughes KS, Schnaper LA, Bellon JR, et al. Lumpectomy plus tamoxifen with or without irradiation in women aged 70 years or older with early breast cancer: long-term follow up of CALBG 9343. J Clin Oncol. 2013;31:2382–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. National Comprehensive Cancer Network. Clinical practice guidelines in oncology: breast version1.2005. Fort Washingtonn, PA: National Comprehensive Cancer Network; 2005. p. BINV-2.

    Google Scholar 

  31. Soulos PR, Yu JB, Roberts KB, et al. Assessing the impact of a cooperative group trial on breast cancer care in the medicare population. J Clin Oncol. 2012;30:1601–7.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Giordano SH. Radiotherapy in older women with low-risk breast cancer: why did practice not change. J Clin Oncol. 2012;30:1577–8.

    Article  PubMed  Google Scholar 

  33. Kunkler IH, Williams LJ, Jack WJ, et al. Breast-conserving surgery with or without irradiation in women aged 65 years of older with early breast cancer (PRIME 11) a randomised controlled trial. Lancet Oncol. 2015;16:266–73.

    Article  PubMed  Google Scholar 

  34. Lockyer AP, Ellis IO, Morgan DAL, et al. Factors influencing local recurrence after excision and radiotherapy for a primary breast cancer. Br J Surg. 1989;76:890–4.

    Article  Google Scholar 

  35. Smitt MC, Nowels KW, Zdeblick MJ, et al. The importance of lumpectomy surgical margin status in longterm results of breast conservation. Cancer. 1995;76:259–67.

    Article  CAS  PubMed  Google Scholar 

  36. Smith IE, Fribbens C. Management of breast cancer in older and frail patients. Breast. 2005;24 Suppl 2:S159–62. https://doi.org/10.1016/j.breast.2015.07.037. Epub 2015 Aug 21 2015

    Article  Google Scholar 

  37. de Glas NA, van de Water W, Engelhardt EG, Bastiaannet E, de Craen AJ, Kroep JR, et al. Validity of Adjuvant! Online program in older patients with breast cancer: a population-based study. Lancet Oncol. 2014;15(7):722–9.

    Article  PubMed  Google Scholar 

  38. Prescott RJ, Kunkler IH, Williams LJ, King CC, Jack W, van der Pol M, Goh TT, Lindley R, Cairns J. A randomised controlled trial of postoperative radiotherapy following breast conserving surgery in a minimum-risk older population. The PRIME trial. Health Technol Assess. 2007;11(31):1–149, iii–iv.

    Article  CAS  PubMed  Google Scholar 

  39. Williams LJ, Kunkler IH, King CC, Jack W, van der Pol M. A randomised controlled trial of post-operative radiotherapy following breast conserving surgery in a minimum-risk older population. Health Technol Assess. 2011;15(12):i–xi, 1–57.

    Article  CAS  PubMed  Google Scholar 

  40. Smith BD, Buccholz TA. Radiation treatments after breast-conserving therapy for elderly patients. J Clin Oncol. 2013;31:2367–8.

    Article  CAS  PubMed  Google Scholar 

  41. Kaidar-Person O, Kuten A, Walker GA, Morgan DAL. Should radiotherapy be omitted in women age 70 years or older with early breast cancer. J Clin Oncol. 2013;31:4569.

    Article  PubMed  Google Scholar 

  42. FAST Trialists group, Agrawal RM, Alhasso A, et al. First results of the randomised UK FAST trial of radiotherapy hypofractionation for treatment of early breast cancer (CRUKE/04/015). Radiother Oncol. 2011;100:93–100.

    Article  Google Scholar 

  43. Haviland JS, Owen JR, Dewar JA, Agrawal RK, Barrett J, Barrett-Lee PJ, Dobbs HJ, Hopwood P, Lawton PA, Magee BJ, Mills J, Simmons S, Sydenham MA, Venables K, Bliss JM, Yarnold JR, START Trialists’ Group. The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. Lancet Oncol. 2013;14:1086–94.

    Article  PubMed  Google Scholar 

  44. Whelan TJ, Pignol JP, Levine MN, Julian JA, MacKenzie R, Parpia S, Shelley W, Grimard L, Bowen J, Lukka H, Perera F, Fyles A, Schneider K, Gulavita S, Freeman C. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med. 2010;362(6):513–20.

    Article  CAS  PubMed  Google Scholar 

  45. Wang S, Kelly G, Gross C, Killelea BK, Mougalian S, Presley C, et al. Information needs of older women with early-stage breast cancer when making radiation therapy decisions. Int J Rad Oncol Biol Phys. 2017;98:733–40.

    Article  Google Scholar 

  46. Scottish Intercollegiate Guidelines Network (SIGN). Treatment of primary breast cancer. Edinburgh: SIGN; 2013. (SIGN publication no. 134). [September 2013]. Available from URL: http://www.sign.ac.uk

    Google Scholar 

  47. Plichta JK. Omitting radiation in older breast cancer patients. Am J Hematol Oncol. 2016;12:12–5.

    Google Scholar 

  48. Jagsi R. Progress and controversies: radiation therapy for invasive breast cancer. CA Cancer J Clin. 2014;64:135–52.

    Article  PubMed  Google Scholar 

  49. Early and locally advanced breast cancer: diagnosis and management. Draft guidelines 2018, National Institute for Care and Clinical Excellence: https://www.nice.org.uk/guidance/indevelopment/gid-ng10016/documents.

  50. Cannon DM, McHaffie DR, Patel PR, et al. Locoregional recurrence following accelerated partial breast irradiation for early-stage invasive breast cancer. Significance of oestrogen receptor status and other pathological variables. Ann Surg Oncol. 2013;20:3446–2013.

    Article  PubMed  Google Scholar 

  51. Bane AL, Whelan TJ, Pond GR, et al. Tumor factors predictive of response to hypofractionated radiotherapy in a randomized trial following breast conserving surgery. Ann Oncol. 2014;25:992–8.

    Article  CAS  PubMed  Google Scholar 

  52. Kirwan CC, Coles CE, Bliss J, et al. It’s PRIMETIME. Postoperative avoidance of radiotherapy: biomarker selection of women at very low risk of local recurrence. Clin Oncol (R Coll Radiol). 2016;28:594–6.

    Article  CAS  Google Scholar 

  53. Harris JR. The PRECISION trial (profiling early breast cancer for radiotherapy omission). A phase II study of breast –conserving surgery without adjuvant radiotherapy for favourable-risk breast cancer. Available at https://clinicaltrials.gov/ct2/show/NCT02653755.2016.

  54. Bartelink H, Horiot J-C, Poortsman PM, et al. Impact of a higher radiation dose on local control and survival in breast-conserving therapy of early breast: 10-year results of the randomized boost versus no boost EORTC 22881-10882 trial. J Clin Oncol. 2007;25:3259–65.

    Article  PubMed  Google Scholar 

  55. Bartelink H, Maingon P, Poortmans P, et al. Whole-breast irradiation with or without a boost for patients treated with breast-conserving surgery for early breast cancer:20 year follow-up of a randomised phase3 trial. Lancet Oncol. 2015;16:47–56.

    Article  PubMed  Google Scholar 

  56. Vrieling C, van Werkhoven E, Maingon P, et al. European Organisation for Research and Treatment of Cancer, Radiation Oncology and Breast Cancer Groups. Prognostic Factors for Local Control in Breast Cancer After Long-term Follow-up in the EORTC Boost vs No Boost Trial: A Randomized Clinical Trial. JAMA Oncol. 2017;3:42–8.

    Article  PubMed  Google Scholar 

  57. Cuttino LW, Kubicky CD. Who benefits from a tumor bed boost after whole-breast radiotherapy? JAMA Oncol. 2017;3:21–2.

    Article  PubMed  Google Scholar 

  58. Hickey BE, Lehman M, Francis DP, See AM. Partial breast irradiation for early breast cancer. Cochrane Database Syst Rev. 2016;7:CD007077. https://doi.org/10.1002/14651858.CD007077.pub3.

    Article  PubMed  Google Scholar 

  59. Coles CE, Griffin CL, Kirby AM, et al. IMPORT Trialists. Partial-breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial): 5-year results from a multicentre, randomised, controlled, phase 3, non-inferiority trial. Lancet. 2017;390:1048–60.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Olivotto IA, Whelan TJ, Parpia S, et al. Interim cosmetic and toxicity results from RAPID: a randomized trial of accelerated partial breast irradiation using three-dimensional conformal external beam radiotherapy. J Clin Oncol. 2013;31:4038–45.

    Article  PubMed  Google Scholar 

  61. Meattini I, Saieva C, Marrazzo L, Di Brina L, et al. Accelerated partial breast irradiation using intensity-modulated radiotherapy technique compared to whole breast irradiation for patients aged 70 years or older: subgroup analysis from a randomized phase 3 trial. Breast Cancer Res Treat. 2015;153:539–47.

    Article  CAS  PubMed  Google Scholar 

  62. Veronesi U, Orrechia R, Maisonneuve P, et al. Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial. Lancet Oncol. 2013;14:1269–77.

    Article  PubMed  Google Scholar 

  63. Vaidya JS, Wenz F, Bulsara M, et al. Risk-adapted targeted intra-operative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A trial. Lancet. 2014;383:603–13.

    Article  PubMed  Google Scholar 

  64. Cuzick J. Radiotherapy for breast cancer, The TARGIT-A trial. Lancet. 2014;383:1716.

    Article  PubMed  Google Scholar 

  65. Haviland J, A’Hern R, Bentzen S, et al. Radiotherapy for breast cancer the TARGIT-A trial. Lancet. 2014;383:1716–7.

    Article  PubMed  Google Scholar 

  66. Hepel J, Wazer D. A flawed study should not define a new standard of care. Int J Rad Oncol Biol Phys. 2015;91:255–7.

    Article  Google Scholar 

  67. Darby SC, Cutter DJ, Boerma M, et al. Radiation-related heart disease: current knowledge and future prospects. Int J Rad Oncol Biol Phys. 2010;76:656–65.

    Article  Google Scholar 

  68. Strnad V, Ott OJ, Hildebrandt G, et al. 5-year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: a randomised, phase 3, non inferiority trial. Lancet. 2016;387:229–38.

    Article  PubMed  Google Scholar 

  69. Schafer R, Strnad V, Polgar C, Uter W, Hildebrandt D, Ott OJ, et al. Quality-of-life for accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation in early breast cancer after breast-conserving surgery (GEC-ESTRO): 5-year results of a randomised, phase 3 trial. Lancet Oncol. 2018;19(6):834–44. https://doi.org/10.1016/S1470-2045(1)30195-5.

    Article  PubMed  Google Scholar 

  70. Tsoutsou PG, Sozzi WJ, Ozsahin M, Delaloue J-F, Bourhis J. Radiotherapy options after breast-conserving surgery: how can selection of patients be refined? J Clin Oncol. 2013;31:4570.

    Article  PubMed  Google Scholar 

  71. Lightowlers SV, Boersma LJ, Fourquet A, et al. Preoperative breast radiation therapy: indications and perspectives. Eur J Cancer. 2017;82:184–92.

    Article  CAS  PubMed  Google Scholar 

  72. Van der Leij F, Bosma SCJ, van der Vijver MJ, Wesseling J, Vreesswijk S, Rivera S, et al. First results of the preoperative accelerated partial breast irradiation (PABPI) trial. Radiother Oncol. 2015;114:322–7.

    Article  PubMed  Google Scholar 

  73. Horton JK, Blitzllau RC, Yoo S, Geradts J, Chang Z, Baker JA, et al. Preoperative single-fraction partial breast radiotherapy-novel phase 1 dose escalation protocol with radiation response biomarkers. Int J Rad Oncol Biol Phys. 2015;92:846–55.

    Article  Google Scholar 

  74. Mamtani A, Gonzalez JJ, Neo DT, Friedman RS, Recht A, Hacker MR, Sharma R. Treatment strategies in octogenarians with early-stage, high-risk breast cancer. Ann Surg Oncol. 2018;25(6):1495–501.

    Article  PubMed  PubMed Central  Google Scholar 

  75. EBCTCG (Early Breast Cancer Trialists’ Collaborative Group), McGale P, Taylor C, Correa C, et al. Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet. 2014;383:2127–35.

    Article  Google Scholar 

  76. Kunkler IH, Canney P, van Tienhoven G, Russell NS, MRC/EORTC (BIG 2-04) SUPREMO Trial Management Group. Elucidating the role of chest wall irradiation in ‘intermediate-risk’ breast cancer. Clin Oncol (R Coll Radiol). 2008;20(1):31–4.

    Article  CAS  Google Scholar 

  77. Curigliano G, Burstein HJ, P Winer E, et al. De-escalating and escalating treatments for early-stage breast cancer: the St Gallen International Expert Consensus Conference on the primary therapy of early breast cancer 2017. Ann Oncol. 2017;28(8):1700–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Recht A, Comen EA, Fine RE, et al. Postmastectomy radiotherapy: an American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology focused guideline update. J Clin Oncol. 2016;34:4431–42.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Edinburgh Cancer Research Centre, Institute of Genetic and Molecular Medicine, University of Edinburgh, Edinburgh, UK

    Ian Kunkler

Authors
  1. Ian Kunkler
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Brighton and Sussex Medical School, Brighton, UK

    Malcolm Reed

  2. Department of Surgery, Sahlgrenska University Hospital, Institute of Clinical Sciences, Gothenburg, Sweden

    Riccardo A. Audisio

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kunkler, I. (2019). Adjuvant Radiotherapy. In: Reed, M., Audisio, R. (eds) Management of Breast Cancer in Older Women. Springer, Cham. https://doi.org/10.1007/978-3-030-11875-4_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-11875-4_11

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-11874-7

  • Online ISBN: 978-3-030-11875-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation