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Challenges in Breast Cancer Irradiation

Early-stage breast cancer

  • Treatment benefits
  • Clinical challenge
  • Clinical solution
  • ZEISS solution

Intraoperative radiotherapy (IORT) is an effective treatment for patients and a sustainable radiotherapy option for societies

Treatment benefits

  • Clinical effectiveness

    IORT can be used to sterilize the tumor bed by changing the tumor bed microenvironment, increase the local control and overall survival and in recurrent cases lower the risk of distant metastases compared to conventional radiotherapy.1,2,3,4,5

  •

    Serving patient needs

    IORT causes less radiation-induced side-effects, less pain and better cosmetic outcomes, offers selected patients with recurrent tumors the option of a subsequent breast-conserving treatment and is generally safer for populations at risk, e.g. smokers or patients with a cardiac disease compared to the standard of care.5,6,7,8,9,10

  •

    Sustainable & cost-effective

    IORT helps to reduce total treatment cost burden, increase quality-adjusted life years (QALY), free-up hospital resources and patient throughput while also being a more sustainable treatment due to less waste, power consumption and travel for global healthcare systems compared to the standard of care.11,12,13

Providing a personalized radiotherapy treatment that saves lives of more patient groups and populations at risk, eliminates conventional radiotherapy side-effects, increases QALYs and helps global societies to reduce their resource and cost burden while providing more value-based healthcare

Clinical challenge

Irradiating breast cancer by delivering the necessary dose immediately and precisely to the tumor bed while not causing collateral damage to surrounding healthy tissue, such as the heart, the lung or other sensitive areas, remains a challenge for conventional radiotherapy treatments.

The usual time gap between surgery and conventional radiotherapy as well as the irradiation of healthy tissue can lead to (faster) local recurrences and radiation-induced side effects which both may result in a shorter overall survival for the patient. Additionally, conventional treatment options can cause more pain and show decreasing cosmetic result for patients, reducing their quality of life.2,14

Using IORT as a versatile single-dose or boost treatment

Clinical solution

  • Within conventional radiotherapy treatment schemes, there is a time gap of typically 4-6 weeks between breast-conserving surgery (BCS) and follow-up irradiation. During this time gap the body starts a biological wound healing response. In the course of this process, the wound fluid stimulates cell growth, including the proliferation, migration, and invasion of residual tumor cells, thereby potentially causing the tumor to re-grow. IORT applied directly during surgery sterilizes the tumor bed, establishes an anti-tumorigenic microenvironment in the breast, and beneficially alters the wound fluid to prevent tumor re-growth.2,3,4

  • IORT has demonstrated that it can increase the overall survival as well as reduce the non-breast cancer related deaths of patients compared to EBRT.1

Lower the risk of local recurrence by changing the tumor bed micro-environment already during surgery and also increase the overall survival

IORT during breast cancer treatment enables the delivery of local high doses to sterilize the tumor bed which establishes an anti-tumorigenic microenvironment in the breast still during surgery. This is due to the fact, that immediate irradiation after breast tumor resection positively affects the tumor bed tissue and proliferation of wound fluid.2,3,4  Additionally, clinical results have demonstrated that the use of IORT increases the overall survival in early breast cancer patients compared to EBRT.1,5  

[...] TARGIT-IORT is not only an effective but can be in many ways a better treatment for early stage breast cancer patients. Every hospital where breast cancer surgery is performed should offer this form of radiation treatment to their breast cancer patients. [...] It should be considered the new standard of treatment for early stage breast cancer [...]

Valery Uhl, MD

Board Certified Radiation Oncologist and President of the TARGIT Collaborative Group (TCG) Society

  • IORT can be applied as a single-dose for selected patients or given as a boost treatment in combination with conventional radiotherapy. Both options cause a much shorter overall radiotherapy scheme compared to non-IORT treatment courses only.13,14

  • Objective assessments of cosmetic outcomes after targeted intraoperative radiotherapy compared with EBRT over the years show a very good IORT cosmesis over time while EBRT decreases.8,9

  • Radiation-related pain symptoms in patients with breast cancer show a significantly lower risk of developing moderate to severe pain for IORT patients compared to EBRT patients.10

Patients benefit from less radiation-induced side-effects compared to the standard of care and in case of recurrent tumors selected patients have the option of a subsequent breast-conserving treatment

Besides the immediate effect IORT has on the tumor bed environment, clinical results also prove that a one-shot IORT treatment can replace up to 15-30 fractions of conventional EBRT treatments for 80% of patients1 if given as a boost, speeding up the overall radiotherapy treatment for care-givers and patients. This is not only greatly reducing the number of necessary hospital visits during the treatment course but also more convenient for patients. IORT results in less radiation scattering to organs at risk and causes less radiation-induced side effects the patient can feel compared to EBRT, e.g. less moderate to severe pain and better cosmetic outcomes, as proven by objective assessments over time and patient self-reported data.1,5,8,9,10 Thus, for most patients and especially for risk populations, e.g. patients with cardiac diseases or smokers, IORT is a safer breast cancer treatment option compared to the standard of care.6,7,9,16

IORT is a favorable clinical, cost-effective and more sustainable treatment option for global healthcare systems compared to the standard of care

Besides the depicted medical effectiveness IORT also has a very positive societal effect, as it helps to substantially reduce the burden for patients, the overall and real treatment costs compared to EBRT by more than 50% while demonstrating an increased QALY value compared to the current standard of care.11,12  Therefore, it enables care-givers to free-up hospital resources for selected patients to increase the overall patient throughput in the radiotherapy department.

Summarizing, IORT offers a significantly more sustainable radiotherapy option compared to the standard of care due to less waste, use of power and travel times11,13 and demonstrates treatment effectiveness without heterogenity between countries and healthcare systems1, a true value-add for every healthcare provider.

Single dose intra-operative radiotherapy for early stage breast cancer can be a better alternative to conventional whole breast radiotherapy for most patients during primary tumor management.

Professor Jayant Vaidya

Professor of Surgery and Oncology and Consultant Surgeon at the University College London (UK) and Chief Principal Investigator of the TARGIT-A study

IORT sustainability effect for eligible breast cancer patients annual, area-wide use in UK
  • 1,200

    carbon emissions lowered by 1,200 tonnes
    (equivalent to 100 hectaes of forest)13

  • 170,000

    170,000 hours of lifetime saved
    (can be used instead for childcare, volunteer work, or paid work for example)13

  • 8 million

    8 million fewer commuting kilometers
    (traveling to clinic)13

These excellent results provide real clinical justification for single intraoperative radiation in suitable patients with early breast cancer. It is now essential to develop the corresponding treatment guidelines as soon as possible.

Professor Jeffrey Tobias

Professor of Oncology at the University College London (UK) and joint initiator of the TARGIT-A study

  • 1

    Vaidya, J. S., et al. (2020). Long-term survival and local control outcomes from single dose targeted intraoperative radiotherapy during lumpectomy (TARGIT-IORT) for early breast cancer: TARGIT-A randomised clinical trial. BMJ, 370, m2836. https://doi.org/10.1136/bmj.m2836
  • 2

    Linares-Galiana, I., et al. (2021). Changes in peripheral immune cells after intraoperative radiation therapy in low-risk breast cancer. J Radiat Res. 2021 Jan 1;62(1):110-118. doi: 10.1093/jrr/rraa083.
  • 3

    Fabris, L., et al. (2016). Radiotherapy-induced miR-223 prevents relapse of breast cancer by targeting the EGF pathway. Oncogene 35, 4914–4926 doi:10.1038/onc.2016.23
  • 4

    Belletti, B., et al. (2008). Targeted intraoperative radiotherapy impairs the stimulation of breast cancer cell proliferation and invasion caused by surgical wounding. Clin Cancer Res 14(5):1325–32. doi:10.1158/1078-0432.CCR-07-4453
  • 5

    Kolberg, H-C., et al. (2022). Breast preservation after local recurrence of breast cancer: Comparison of length and quality of life (QoL) between breast conserving surgery with intraoperative radiotherapy (TARGIT-IORT) versus mastectomy. Journal of Clinical Oncology 2022 40:16_suppl, e12573-e12573.
  • 6

    Stefanovic, S., et al. (2021). Cardiac serum marker alterations after intraoperative radiotherapy with low-energy x-rays in early breast cancer as an indicator of possible cardiac toxicity. Strahlenther Onkol. 2021 Jan;197(1):39-47. doi: 10.1007/s00066-020-01671-3.
  • 7

    Kolberg, H-C., et al. (2022). Impact of targeted intraoperative (TARGIT-IORT) tumor bed boost during breast conserving surgery for early breast cancer on breast cancer and non-breast cancer associated mortality and morbidity. Cancer Res (2022) 82 (4_Supplement): P3-19-16. https://doi.org/10.1158/1538-7445.SABCS21-P3-19-16
  • 8

    Corica, T., et al. (2018). Cosmetic outcome as rated by patients, doctors, nurses and BCCT. core software assessed over 5 years in a subset of patients in the TARGIT-A Trial. Radiation Oncology (2018) 13:68. https://doi.org/10.1186/s13014-018-0998-x
  • 9

    Keshtgar, M. R., et al. (2013) Objective assessment of cosmetic outcome after targeted intraoperative radiotherapy in breast cancer: results from a randomised controlled trial. Breast Cancer Research and Treatment 140, pages 519–525, doi.org/10.1007/s10549-013-2641-8
  • 10

    Welzel, G., et al. (2013) Radiation-related quality of life parameters after targeted intraoperative radiotherapy versus whole breast radiotherapy in patients with breast cancer: results from the randomized phase III trial TARGIT-A. Radiation Oncology Journal 8, 9. doi.org/10.1186/1748-717X-8-9
  • 11

    Vaidya, J. S., et al. (2017). Health economics of targeted intraoperative radiotherapy (TARGIT- IORT) for early breast cancer: a cost- effectiveness analysis in the United Kingdom. BMJ Open 7: e014944. doi:10.1136/bmjopen-2016-014944
  • 12

    Monten, C., et al. (2017). Adjuvant breast radiotherapy: How to trade-off cost and effectiveness?. Radiother Oncol, https://doi.org/10.1016/j.radonc.2017.11.005
  • 13

    Coombs, N. J., et al. (2016). Environmental and social benefits of the targeted intraoperative radiotherapy for breast cancer: data from UK TARGIT-A trial centres and two UK NHS hospitals offering TARGIT IORTBMJ Open 2016;6:e010703. doi: 10.1136/bmjopen-2015-010703
  • 14

    Vaidya, J. S., et al. (2010). Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial. Lancet, 376(9735), 91–102. https://doi.org/10.1016/S0140-6736(10)60837-9
  • 15

    Vaidya, J. S., et al. (2011). Long-term results of targeted intraoperative radiotherapy (Targit) boost during breast-conserving surgery. International journal of radiation oncology, biology, physics, 81(4), 1091–1097. https://doi.org/10.1016/j.ijrobp.2010.07.1996
  • 16

    Kolberg, H-C., et al. (2017). Targeted intraoperative radiotherapy tumour bed boost during breast conserving surgery after neoadjuvant chemotherapy – a subgroup analysis of hormone receptor-positive HER2-negative breast cancer. Breast Care 12:318–323. DOI:10.1159/000479424.