Accelerated Partial Breast Irradiation FACTS & MYTHS

Accelerated Partial Breast Irradiation (APBI) Accelerated Partial Breast Irradiation FACTS & MYTHS V.Strnad Radiation options after breast conserving surgery Whole Breast Irradiation (EBRT) APBI technique options Boost technique options IORT External Beam Brachytherapy External Beam Brachytherapy IORT Linac 50 kv X-ray Multicatheter interstitial Single catheter HDR/PDR interstitial Linac 50 kv X-ray WHO CAN, DO IT. WHO CANNOT, COMBATS IT

APBI current methods 1. External beam radiation therapy with 6 MeV (IMRT) 2. Intraoperative radiation therapy with electrons (Linac) 3. Intraoperative radiation therapy with 50kV Röntgen-machine ( Intrabeam ) Phase III trials!? 4. Single-catheter brachytherapy Proxima-catheter SAVI-catheter Contura-catheter Electronic brachytherapy 5. Multicatheter interstitial brachytherapy 5 5 Gy at 10 mm!!

APBI using external beam radiation

APBI Phase 3 trials using external beam radiation Median follow-up 36 months Side effets Cosmesis p=0.002

Median follow-up 5 yeears N=520 APBI Phase 3 trials using external beam radiation 1.5%

Median follow-up 5 years APBI Phase 3 trials using external beam radiation

APBI using single fraction IORT 21 Gy 50-kV Röntgen-machine 5 5 Gy at 10 mm!!

APBI Phase 3 trial using of IORT with Linac

Results of IORT using Linac

APBI Phase 3 trial using IORT with Intrabeam (50 kv Röntgen-machine) Follow-up (Median): 2.5 years!!

APBI using balloon single catheter brachytherapy (Mammosite) Single dwell position at the center of the balloon Multi-dwell positions along active length of the catheter

Balloon Mammosite-System MammoSite Breast Brachytherapy Registry Trial

Balloon Mammosite-System Mastectomy risk, Smith et al. SABCS December 2011 brachytherapy with MammoSite: 3.95% MammoSite Breast Brachytherapy Registry Trial risk % EBRT: 2.18% years Smith GL, Xu Y, Buchholz TA, Giordano SH, Jiang J, Shih YC, Smith BD Association Between Treatment With Brachytherapy vs Whole-Breast Irradiation and Subsequent Mastectomy, Complications, and Survival Among Older Women With Invasive Breast Cancer. JAMA 2012 May 2;307(17):1827-1837.

APBI using multicatheter balloon systems SAVI, ClearPath, Contura

APBI using multicathter interstitial brachytherapy WS ETB CTV PTV ImTV 15mm 18mm 10mm

Multicatheter Brachytherapy for Partial Breast Irradiation FACTS & MYTHS Facts 1) Longest experiences among all APBI techniques 2) Variability, versatility, precision. 3) High Quality assurance and reproducibility. 4) No dependence on patient motions. Myths 1) Painful technique, scars remains. 2) Bad accceptance by patients. 3) Large experience and skill of physicians necessary. 4) The patients in Europe don t have any (travel) problem with utilization of EBRT 5) No long term results

Multicatheter Brachytherapy for Partial Breast Irradiation FACTS & MYTHS Facts 1) Longest experiences among all APBI techniques 2) Variability, Vielseitigkeit, precision of brachytherapy techniques. 3) High Quality assurance and reproducibility. Interstitial brachytherapy for breast cancer has been started 4) No dependence >45 years on ago patient!! motions. The basic rules of interstitial brachytherapy has been defined in Myths the same time 1) Painfull First technique, APBI Phase scars II trials remains. started >20 years ago. 2) Bad accceptance Development by and patients. definition of basic rules of Image-guided 3) Large brachytherapy experience and techniques skill of physicians in the necessary. same time. In this time versatile different brachytherapy techniques has been developed: Multi-Catheter techniques & Single-Catheter techniques.

Multicatheter Brachytherapy for Partial Breast Irradiation FACTS & MYTHS Fact is that multicatheter brachytherapy technique offer to physician and to the patient: 1)Longest experiences among all APBI techniques a. Technique b. Results 2) Variability, versatility, precision 3) High Quality assurance and reproducibility. 4) No dependence on patient motions. Myths 1) Painfull technique, scars remains. 2) Bad accceptance by patients. 3) Large experience and skill of physicians necessary.

Multicatheter Brachytherapy for Partial Breast Irradiation FACTS & MYTHS 2) Variability, versatility, precision. 3) High Quality assurance and reproducibility. 4) No dependence on patient motions. Multicatheter brachytherapy EBRT

Multicatheter Brachytherapy for Partial Breast Irradiation FACTS & MYTHS Facts 1) Longest experiences among all APBI techniques a. Technique 2) Variability, versatility, precision (Coverage ~ V100 95%). 3) High Quality assurance and reproducibility. 4) No dependence on patient motions. Myths 1) Painfull technique, scars remains. 2) Bad accceptance by patients. 3) Large experience and skill of physicians necessary. 4) The patients in Europe don t have any (travel) problem with utilization of EBRT 5) No long term results

Multicatheter Brachytherapy for Partial Breast Irradiation FACTS & MYTHS Myths 1) Painfull technique, scars remains. not true

Multicatheter Brachytherapy for Partial Breast Irradiation FACTS & MYTHS Myths 2) Bad accceptance by patients. not true Accelerated partial breast irradiation via brachytherapy: A patternsof-care analysis with ASTRO consensus statement groupings Brachytherapy, 10, 2011, 479-485 Zain A. Husain et al.

Multicatheter Brachytherapy for Partial Breast Irradiation FACTS & MYTHS Myths 3) Large experience and skill of physicians necessary consequently very scarely used technique.. Experience and skill are necessary but as for every medical ectivities!! Technique is very easy!

Multicatheter Brachytherapy for Partial Breast Irradiation FACTS & MYTHS Myths 3) Large experience and skill of physicians necessary consequently very scarely used technique..

Multicatheter Brachytherapy for Partial Breast Irradiation FACTS & MYTHS Myths 4) The patients in Europe don t have any (travel) problem with utilization of EBRT not true for Germany, France, Russia, China, India, Brasil Netherlands, Luxembourg Germany, France, Spain, Russia 67.5 km

APBI using multicatheter brachytherapy - Phase II trials Author/Study Polgar et al., 2012 Hungarian National Institute of Oncology, Phase II, Budapest Johansson et al., 2009 Örebro Med. Centre, Phase II, Örebro King, Kuske et al., 2000 Ochsner Clinic, Phase II, New Orleans Polgar et al, 2013 Hungarian National Institute of Oncology, Phase III, Budapest Arthur et al., 2008 Multicentric Phase II, RTOG 95-17 Mark et al., 2009 J Arrington Cancer Center, Phase II, Lubbock Antonucci, Vicini et al., 2011 William Beaumont Hospital, Phase II, Detroit Strnad et al., 2012 Multicentric Phase II, German-Austrian Study, Erlangen, Leipzig, Vienna, Linz Wilkinson, Beitsch Chen, Vicini et al. [diff APBI techniques] 2012 San Antonio Breast Cancer Symposium Kamrava, Kuske et al., 2015 Multi-Institutional Study Number of pts (n) Median follow-up (years) Local recurrences (%) (95% CI) (n) 45 13,8 11.9 (15 y.) (2.5 21.2) (4/45) 50 7,2 4.0 (1.2 16.2) (3/51) 51 6,25 2.0 (0.05 10.5 ) (1/51) 10,8 5.9 (1.3 11.2) (4/88) 99 7 6.1 (2.3 12.7) (6/99) 192 5,4 4.2 (1.8 8.0) (8/192) 199 9,6 5.0 (2.4 9.1) (10/199) 274 8 2.9 (1.3 5.7) (8/274) 88*/258 * treated with brachytherapy Annual local recurrences % 0,79 0,57 0,32 0,59 0,87 0,78 0,52 0,55 2.127 6 4.0 0,66 (3,2-5,7) 1356 6,7 3.8 0,93 Chen et al., ABS Annual Meeting 2014 W.Beaumont Health System, Royal Oak Young et al., ABS Annual Meeting 2014 Cancer Center, Oklahoma City 484 8 1,3-2.5 (5 y.), 0,25-0,5 2.5-4.6 (10y.) 241 5,5 1.54 0,28 University Hospital (4/241) Erlangen TOTAL 4.986 0,6 (mean)

APBI using multicatheter brachytherapy: largest Match pair analysis & largest Phase II trial 12 y. 3.8% vs 5 % 98% 95% 5 y. 8 y.

APBI using multicatheter brachytherapy largest retrospective analysis Median follow-up: 6.7 y.

APBI using multicatheter brachytherapy Phase III trial limited the statistical power

GEC-ESTRO Phase III multicentric APBI trial. Barcelona (Spain) Bern (Switzerland) Brno (Czech Rep.) Budapest (Hungary) Erlangen (Germany) Jena (Germany) Kiel (Germany) Münster (Germany) Leipzig (Germany) Lübeck (Germany) Regensburg (Germany) Rostock (Germany) Valencia (Spain) Vienna (Austria) Warszaw (Poland) Würzburg (Germany) www.apbi.uni-erlangen.de

GEC-ESTRO Phase III multicentric APBI trial. A prospective, randomized, multicentric phase III-trial; non-inferiority trial, analysis of results ~ as treated Stratification: with respect to center, invasive vs. non-invasive disease, and pre- vs. post-menopausal status. n= 1184 patients Breast conserving surgery low risk breast cancer stratification Accelerated Partial Breast Irradiation APBI (n=633) Whole Breast radiation therapy WBRT (n=551)

APBI using multicatheter brachytherapy GEC-ESTRO Phase III trial see please soon by:. already accepted.

Multicatheter Brachytherapy for Partial Breast Irradiation FACTS & MYTHS SUMMARY OF MYTHS MYTHS It s true? Painfull technique, scars remains NO Bad accceptance by patients NO Experience and skill of physicians necessary. YES The patients in Europe don t have any (travel) problem with utilization of EBRT No long term results NO NO

Brachytherapy for Partial Breast Irradiation FACTS & MYTHS

Brachytherapy for Partial Breast Irradiation FACTS & MYTHS ~ Summary 5 point score system Comparison of APBI using brachytherapy versus APBI using EBRT versus APBI using IORT Facts Multicathetecatheter (IMRT) Single- EBRT IORT-Linac IORT-50kV- X-ray Long term experience with this technique Long term results publ.(y.) Variability / Coverage +++++ (>20 years) +++++ (>12 years) +++++ (10 years) ++++ (5 years) +++ (5 years) ++ (2 years) +++++ (10 years) ++++ (4-5 years) ++++ (5-7 years) ++ (2.5 years) +++++ ++ +++++ ++++ - Versatility +++++ + +++++ ++++ - Precision +++++ +++++ ++++ +++++ +++++ Independence on patient motion High level of QA and reproducibility +++++ +++++ ++ +++++ +++++ +++++ +++++ ++++ +++++ +++++ TOTAL (points) 35 28 26 32 21

Accelerated Partial Breast Irradiation SUMMARY (1) Results of APBI using IORT (Intrabeam, Linac) are at the moment disappointing negative (2) Results of APBI using IMRT (external beam radiation therapy) are at the moment controversial, published results are negative (3) Results of APBI using multicatheter brachytherapy are current excellent. (4) Selection guidelines for appropriateness of APBI using brachytherapy will need to be constantly refined to reflect the ever-accumulating published results of clinical outcomes. Particular help will come from the recently closed GEC-ESTRO and NSABP B- 39/RTOG 0413 trials.