For our September #radonc #jc we will be discussing partial breast irradiation (PBI), focusing on intraoperative radiation therapy (IORT) as part of breast conserving therapy. As the trend toward de-escalation continues in local therapy, IORT raises questions about patient selection for no radiation, partial breast irradiation, or whole breast irradiation..
This coming weekend, we will review an update of the randomized trial, TARGIT-A:
The article is free for download. Professor Jayant Vaidya, breast surgeon at UCL Cancer Institute, and Dr. Elena Sperk, radiation oncologist in Mannheim Germany, will join us this weekend to discuss this multicenter randomized trial, along with some coauthors. The chat will start at 8AM CST on Saturday, September 19th and continue through Sunday, September 20th to facilitate global participation.
Because this treatment technique is less frequently done than whole breast radiation or other forms of PBI, we plan to cover more questions and omit a live hour discussion.
We will focus on the following topics:
T1: The original hypothesis for TARGIT-A was that partial breast irradiation limited to the surgical cavity was sufficient for early stage breast cancer. Can you explain the study design and what pragmatic design means?
T2: In the IORT arm, supplemental external beam radiotherapy was used if margins were <1mm or if there was >25% DCIS (EIC). Do current recommendations for adequate margins change whether these are still reasons for EBRT?
T3: How does IORT work (type of unit, setup, treatment planning, OR resources)? How does the dosimetry of IORT differ from other breast techniques, especially HDR brachytherapy APBI?
T4: Based upon the trial design, it appears evenly balanced between receptor status and HER2/neu expression. Do you have any data on differences in the arms by St.Gallen’s classification?
T5: BRCA testing has evolved over time, including wider accessibility. How did that change accrual and evaluation for enrolled patients in TARGIT-A? –What about OncotypeDX use?
T6: Patients joined the steering committee of TARGIT-A as the trial opened, which has become much more common now. From your perspective, how has including patients in the clinical trial been beneficial? Are there barriers to patient inclusion for trial design at the outset?
T7: What is a noninferiority trial? Why did you choose this design?
T8: What were the key breast cancer-related outcomes that should interest clinicians in discussing the best options for adjuvant radiation, if offered at all?
T9: Depending upon the setting, implementing IORT may require shifting initial consultations to discuss adjuvant radiotherapy preoperatively. How has that influenced the patient-physician relationship with the clinical oncologist/radiation oncologist compared to postoperative evaluation?
T10: What are the health economics, and what assumptions are needed to make it work?
T11: Given contemporary changes in our understanding of cancer biology, changes in surgical techniques, who are the ideal candidates for IORT with 50 kV photons?
Here are guidelines on how to sign up and participate
Any suggestions? Leave a comment or tweet us at @Rad_Nation. Looking forward to seeing everyone this weekend!
1. Vaidya JS, Bulsara M, Baum M, et al. 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. 2020;370:m2836. https://www.bmj.com/content/370/bmj.m2836
2. Vaidya A, Vaidya P, Both B, Brew-Graves C, Bulsara M, Vaidya JS. Health economics of targeted intraoperative radiotherapy (TARGIT-IORT) for early breast cancer: a cost-effectiveness analysis in the United Kingdom. BMJ Open. 2017;7(8):e014944.
3. Shah C, Wobb J, Khan A. Intraoperative Radiation Therapy in Breast Cancer: Still Not Ready for Prime Time. Annals of Surgical Oncology. 2016;23(6):1796-1798. https://link.springer.com/article/10.1245/s10434-016-5129-z#citeas
4. Fastner G, Gaisberger C, Kaiser J, et al. ESTRO IORT Task Force/ACROP recommendations for intraoperative radiation therapy with electrons (IOERT) in breast cancer. Radiotherapy and Oncology. 2020;149:150-157. https://www.thegreenjournal.com/article/S0167-8140(20)30240-1/abstract
5. Veronesi U, Orecchia R, Maisonneuve P, et al. Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial. Lancet Oncol. 2013;14(13):1269-1277. https://linkinghub.elsevier.com/retrieve/pii/S1470-2045(13)70497-2
6. Lorenzen AW, Kiriazov B, De Andrade JP, et al. Intraoperative Radiotherapy for Breast Cancer Treatment in a Rural Community. Ann Surg Oncol. 2018;25(10):3004-3010. https://dx.doi.org/10.1245/s10434-018-6574-7
7. Correa C, Harris EE, Leonardi MC, et al. Accelerated Partial Breast Irradiation: Executive summary for the update of an ASTRO Evidence-Based Consensus Statement. Practical Radiation Oncology. 2017;7(2):73-79. https://www.practicalradonc.org/article/S1879-8500(16)30184-9/fulltext
8. Herskind C, Wenz F. Radiobiological comparison of hypofractionated accelerated partial-breast irradiation (APBI) and single-dose intraoperative radiotherapy (IORT) with 50-kV X-rays. Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft [et al]. 2010;186(8):444-451. http://europepmc.org/article/med/20803285#impact
9. Kawamura M, Itoh Y, Kamomae T, et al. A phase I/II trial of intraoperative breast radiotherapy in an Asian population: 10-year results with critical evaluation. Journal of Radiation Research. 2020;61(4):602-607. https://academic.oup.com/jrr/article/61/4/602/5850956
10. Hepel J, Wazer DE. A Flawed Study Should Not Define a New Standard of Care. International Journal of Radiation Oncology, Biology, Physics. 2015;91(2):255-257. https://www.redjournal.org/article/S0360-3016(14)04125-X/abstract#%20
11. Vaidya JS, Bulsara M, Wenz F, et al. Pride, Prejudice, or Science: Attitudes Towards the Results of the TARGIT-A Trial of Targeted Intraoperative Radiation Therapy for Breast Cancer. International Journal of Radiation Oncology, Biology, Physics. 2015;92(3):491-497. https://www.redjournal.org/article/S0360-3016(15)00334-X/abstract
12. Balagamwala EH, Manyam BV, Leyrer CM, et al. Most patients are eligible for an alternative to convetional whole-breast irradiation for early-stage breast cancer: a National Cancer Database Analysis. Breast J 2018;24(5):806-810 https://onlinelibrary.wiley.com/doi/abs/10.1111/tbj.13051
13. ClinicalTrials.gov. Intraoperative electron radiotherapy for low-risk early breast cancer (COSMOPOLITAN). 2019. Available from: https://clinicaltrials.gov/ct2/show/study/NCT03838419
14. Sperk E. First per protocol analysis of the Prospective Phase II Study of Intraoperative Radiotherapy (IORT) in Elderly Patients with Small Breast Cancer: Targit E(lderly). Int J Radiat Oncol Biol Phys. 2019 Sep;105(1 Suppl):S8. (Abstract Only) https://www.redjournal.org/article/S0360-3016(19)31228-3/fulltext.
15. Obi E, Tom MC, Manyam BV, et al. Outcomes with intraoperative radiation therapy in early-stage breast cancer. Breast J. 2020;26(3):454-457. https://onlinelibrary.wiley.com/doi/abs/10.1111/tbj.13574