Non-Surgical Breast-Conserving Treatment (KORTUC-BCT) Using a New Radiosensitization Method (KORTUC II) for Patients with Stage I or II Breast Cancer

Abstract

The purpose of the present study was to establish a non-surgical breast-conserving treatment (BCT) using KORTUC II radiosensitization treatment. A new radiosensitizing agent containing 0.5% hydrogen peroxide and 0.83% sodium hyaluronate (a CD44 ligand) has been developed for intra-tumoral injection into various tumors. This new method, named KORTUC II, was approved by our local ethics committee for the treatment of breast cancer and metastatic lymph nodes. A total of 72 early-stage breast cancer patients (stage 0, 1 patient; stage I, 23; stage II, 48) were enrolled in the KORTUC II trial after providing fully informed consent. The mean age of the patients was 59.7 years. A maximum of 6 mL (usually 3 mL for tumors of less than approximately 3 cm in diameter) of the agent was injected into breast tumor tissue twice a week under ultrasonographic guidance. For radiotherapy, hypofraction radiotherapy was administered using a tangential fields approach including an ipsilateral axillary region and field-in-field method; the energy level was 4 MV, and the total radiation dose was 44 Gy administered as 2.75 Gy/fraction. An electron boost of 3 Gy was added three times. Treatment was well tolerated with minimal adverse effects in all 72 patients. No patients showed any significant complications other than mild dermatitis. A total of 24 patients under 75 years old with stage II breast cancer underwent induction chemotherapy (EC and/or taxane) prior to KORTUC II treatment, and 58 patients with estrogen receptor-positive tumors also received hormonal therapy following KORTUC II. The mean duration of follow-up as of the end of September 2014 was 51.1 months, at which time 68 patients were alive without any distant metastases. Only one patient had local recurrence and died of cardiac failure at 6.5 years. Another one patient had bone metastases. For two of the 72 patients, follow-up ended after several months following KORTUC II treatment. In conclusion, non-surgical BCT can be performed using KORTUC II, which has three major characteristics: imaging guidance; enzyme-targeting; and targeting of breast cancer stem cells via the CD44 receptor.

Biological effects of hydrogen peroxide administered intratumorally with or without irradiation in murine tumors

“…In previous publications as well as in our preliminary clinical experiences, the safety of KORTUC treatment has almost been established. (7)(8)(9)(10)(11)18) Intratumoral oxygen pressures at 1 or 24 h after H 2 O 2 -containing sodium hyaluronate injections were reported previously. (13) Oxygen pressures increased to 1400-1600 mmHg 1 h later and decreased to 80-100 mmHg at 24 h. Our CT study results seemed to be consistent with the previous results.…”

“…In previous publications as well as in our preliminary clinical experiences, the safety of KORTUC treatment has almost been established. ()…”

“…In addition, phase I followed by phase II clinical studies were started in 2016 at the Royal Marsden Hospital, London (Y. Ogawa, personal communication, March 2017). There have been no randomized studies, but phase II studies in operable breast cancer patients have indicated definite efficacy . The investigators suggested that this treatment might become an alternative definitive treatment for early and advanced breast cancer in patients who refuse any type of surgery.…”

“…There have been no randomized studies, but phase II studies in operable breast cancer patients have indicated definite efficacy. (18) The investigators suggested that this treatment might become an alternative definitive treatment for early and advanced breast cancer in patients who refuse any type of surgery. Efficacy against other tumors has also been reported.…”

Serial Assessment of Therapeutic Response to a New Radiosensitization Treatment, Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas, Type II (KORTUC II), in Patients with Stage I/II Breast Cancer Using Breast Contrast-Enhanced Magnetic Resonance Imaging

“…Furthermore, cCR was also confirmed through other diagnostic modalities performed during the follow-up period. Actually, the therapeutic effect was evaluated by PET-CT [ 10 ], breast MRI, ultrasonographic examination [ 11 ], and mammography [ 12 ] at approximately 4 months and approximately 10 months after KORTUC II, and these examinations were repeated biannually for at least 5 years after KORTUC II treatment, thereafter. Only one patient (case 5 in Table 1 , Table 2 and Table 3 ) had local recurrence, which was discovered at 39 months; this patient died after 83 months of KORTUC II.…”