Authors:
Dr med Dr phil Takeshi Miyamoto | Gunma prefectural Cancer Center | Japan
Dr med Dr phil Masataka Sawaki | Aichi Cancer Center | Japan
Dr med Akiyo Yoshimura | Aichi Cancer Center | Japan
Dr med Dr phil Tomomi Fujisawa | Gunma prefectural Cancer Center | Japan
Mariko Kawamura | Nagoya University Graduate School of Medicine | Japan
Takeshi Ebara | Gunma prefectural Cancer Center | Japan
Ken Ando | Gunma prefectural Cancer Center | Japan
Jun Eishima | Gunma prefectural Cancer Center | Japan
Hiroyuki Tachibana | Aichi Cancer Center | Japan
Takeshi Kodaira | Aichi Cancer Center | Japan
Toyone Kikumori | Nagoya University Graduate School of Medicine | Japan
Yasuhiro Yanagita | Gunma prefectural Cancer Center | Japan
Hiroji Iwata | Aichi Cancer Center | Japan
[Background] For early breast cancer, breast-conserving surgery and whole breast irradiation 50 Gy (± boost) for remaining breast is the standard treatment. However, because whole breast irradiation costs 5 weeks outpatient treatments, we need to develop new method to shorten the period of irradiation in Japan. Intraoperative irradiation therapy (IORT) for the remain mammary grand (21 Gy/fr), one of the accelerated partial breast irradiation (APBI) methods, with properly case selection was reported to have equal ipsilateral breast tumor recurrence (IBTR) rate comparing with the conventional whole breast irradiation by phase III trial (Veronesi U, Lancet Oncol 2013, Vaidya JS, Lancet 2014, Stmad V, Lancet 2016). This procedure is positioned in suitable group by ASTRO guideline 2017. We performed multicenter phase II study of IORT in early breast cancer (UMIN00003578), because we have no data for Japanese breast cancer patients with IORT.
[Purpose] To investigate the efficacy and safety of IORT.
[Patients and methods] Eligibility criteria: 1) T < 2.5 cm, 2) to have hope for breast conserving surgery, 3) ≥ 50 years old, 4) surgical margin >1cm, 5) intraoperative pathologically free margins, 6) sentinel node negative and 7) written informed consent. Exclusion criteria: 1) contraindications to radiation, 2) past radiation therapy for the same breast or chest, 3) extensive intraductal component, 4) a tumor located in the axillary tail of the breast.
Procedures: 1) sentinel lymph node biopsy, proven to node negative, 2) Partial resection with at least 1cm margin, 3) microscopic assessment of margins by frozen sections, 4) to protect the chest wall, install the lead disk between the grand and major pectoralis muscle, 5) suture of the remaining breast, 6) irradiation of 21 Gy (90% dose), used by MOBETRON® (IntraOp Medical Corporation) or Clinac® 21EX (Varian Medical Systems, Inc.).
Primary endpoint: IBTR rate. Secondary endpoint: safety (or toxicity).
Toxicity was evaluated with the Common Terminology Criteria for Adverse Events (CTCAE) V4.0.
Target number of subjects: 140 cases.
[Results] From April 2010 to April 2015, 142 patients were enrolled and accrual was completed. 129 patients underwent IORT at 21Gy. Median follow up time is 51.5 months (range 30.0-89.0). Stage 0; n=4(3.1%), Stage I; n=98(76.0%), Stage IIA; n=27(20.9%). The intrinsic subtypes of patients were followed, Luminal type; n=116(89.9%), Triple Negative; n=9(7.0%), HER 2; n=4(3.1%). IBTR occurred in 4 cases (3.1%, [95%CI: 0.9-0.78]). Adverse events were, deep connective tissue fibrosis G1: 78.1%, postoperative hemorrhage G 1: 4.7%, wound infection G 3: 1.6%, G 2: 1.6%, G1: 1.6%, soft tissue necrosis G 3: 0.8%, G 2: 0.8%, G1: 1.6%, wound dehiscence G 1: 2.3% and pain G 1: 8.6%.
[Conclusion] IBTR was low in patients with IORT at 21Gy, and this treatment was tolerated well in Japanese women as well as conventional breast irradiation.