A Japanese prospective multi-institutional feasibility study on accelerated partial breast irradiation using multicatheter interstitial brachytherapy: clinical results with a median follow-up of 60 months.

BACKGROUND: We carried out the first multi-institutional prospective study on accelerated partial breast irradiation (APBI) via multicatheter interstitial brachytherapy in a shorter period for early breast cancer in Japan. METHODS: Patient eligibility criteria included positive hormone receptors, tumors ≤ 3 cm and TNM stage pN0M0. After breast-conserving surgery (Japanese cylindrical resection) and histological confirmation of negative surgical margins and the absence of lymph node metastasis, applicator implantation was performed either postoperatively or intraoperatively. High-dose-rate brachytherapy of 36 Gy in 6 fractions was delivered. RESULTS: Forty-six patients from six institutions received this treatment regimen, and the median follow-up time was 60 months (range 57-67 months). The median resected breast tissue volume was 81 cm3 (range 28-260 cm3). No Grade 4 late sequela, local recurrence nor death due to breast cancer were observed. Grade 2-3 sequelae such as rib fracture (2%), soft tissue necrosis (9%), fibrosis (20%), and breast pain (9%) were observed. The resected breast tissue volumes of the patients who had Grade ≥ 2 fibrosis and Grade < 2 fibrosis were 105.9 ± 32.3 cm3 and 76.3 ± 45.6 cm3, respectively, p = 0.02. The overall cosmetic outcome score of Excellent/Good was 74% at 60 months after APBI. Grade ≥ 1 fibrosis was observed in 44% and 92% of patients who scored Excellent/Good and Fair/Poor, respectively, p = 0.004. CONCLUSIONS: This study showed excellent local control and survival results with minimal late sequelae.

Case report of a dose-volume histogram analysis of rib fracture after accelerated partial breast irradiation: interim analysis of a Japanese prospective multi-institutional feasibility study.

We initiated the first multi-institutional prospective study of accelerated partial breast irradiation for early breast cancer in Japan. Our early clinical results showed that the treatment methods were technically reproducible between institutions and showed excellent disease control at a median follow-up of 26 months in our previous report. At present, total 46 patients from six institutions underwent the treatment regimen from October 2009 to December 2011, and the median follow-up time was 60 months (range, 57-67 months). In 46 patients, we experienced one patient who had rib fracture as a late complication. The dose-volume histogram (DVH) result of this patient was analyzed. The D0.01cc, D0.1cc, and D1cc values of the patient were 913, 817, and 664 cGy per fraction, respectively. These values were the highest values in 46 patients. The average D0.01cc, D0.1cc, and D1cc values of the other 45 patients were 546, 500, and 419, respectively, cGy per fraction. From this result, DVH values showing high-dose irradiated volume (D0.01cc, D0.1cc, and D1cc) seem to be a good predictive factor of rib fracture for accelerated partial breast irradiation. However, further investigation is necessary because of the small number of patients investigated.

Uncertainty of cosmetic evaluation after accelerated partial breast irradiation: interim analysis of a Japanese prospective multi-institutional feasibility study.

PURPOSE: We conducted a multi-institutional prospective study on accelerated partial breast irradiation (APBI) using interstitial brachytherapy. The clinical results over a minimum follow-up period of 30 months are presented here. MATERIALS AND METHODS: Forty-six patients with breast cancer were treated with breast-conserving surgery and postoperative APBI. After confirmation of negative surgical margins and negative lymph nodes, a high-dose-rate brachytherapy protocol of 36 Gy/6 fractions was carried out. All clinical data were prospectively collected using the Common Terminology Criteria for Adverse Events ver. 3.0. RESULTS: No recurrence was observed. Cumulative rates of grade 2 or higher late sequelae were 25% for fibrosis, 2% for fractures, 9% for pain, and 9% for soft tissue necrosis. Rates of excellent or good cosmetic results as assessed by the physician and patient were 93 and 89% at the 12-month follow-up and 76 and 74% at the 30-month follow-up, respectively. Large volumes of resected tissue in small breasts were associated with fibrosis of grade 2 or higher. CONCLUSION: APBI in Japanese women provides satisfactory clinical results except for cosmetic outcomes. There is some difficulty with the assessment of fibrosis and cosmetic outcomes, especially in patients with small breasts. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000001677.

A Japanese prospective multi-institutional feasibility study on accelerated partial breast irradiation using interstitial brachytherapy: clinical results with a median follow-up of 26 months.

BACKGROUND: A Japanese prospective multi-institutional feasibility study on accelerated partial breast irradiation using interstitial brachytherapy was performed. The first clinical results were reported with a median follow-up of 26 months. PATIENTS AND METHODS: Forty-six female breast cancer patients with positive hormone receptors and tumors ≤3 cm, pN0M0, completed the protocol treatment. After breast-conserving surgery and histological confirmation of negative surgical margins and pN0, brachytherapy applicators were implanted either postoperatively (n = 45) or intraoperatively (n = 1). High-dose-rate brachytherapy of 36 Gy/6 fractions was delivered. All clinical data were prospectively collected using case report forms and the Common Terminology Criteria for Adverse Events ver.3.0. RESULTS: At the median follow-up of 26 months, no breast cancer recurrence of any type was observed. Sequelae ≥G2 were dermatitis (G2, 7 %), fibrosis (G2, 11 %; G3, 4 %), fracture (G2, 2 %), pain (G2, 7 %; G3, 2 %), and soft tissue necrosis (G2, 6 %). Cosmetic outcomes evaluated by excellent/good scores were 100 % at pre-therapy (n = 46), 94 % at 12 months (n = 46), and 81 % at 24 months (n = 36), respectively. CONCLUSIONS: Disease control and sequelae were satisfactory due to the strict eligibility and protocol-defined treatment parameters. The cosmetic outcomes were comparable to those of previous Japanese breast-conserving therapy series.

A Japanese prospective multi-institutional feasibility study on accelerated partial breast irradiation using interstitial brachytherapy: treatment planning and quality assurance.

BACKGROUND: In Japan, breast-conserving surgery with closed cavity has generally been performed for breast cancer patients, and accelerated partial breast irradiation (APBI) is considered difficult because Asian females generally have smaller breast sizes than Western females. Therefore, common identification of target and treatment plan method in APBI is required. A prospective multicenter study was conducted in Japan to determine institutional compliance with APBI using high-dose-rate interstitial brachytherapy (ISBT) designed for Japanese female patients. METHODS: For this study, 46 patients were recruited at eight institutions from January 2009 to December 2011. The reproducibility of the ISBT-APBI plan was evaluated using three criteria: (1) minimum clinical target volume dose with a clip dose ≥ 6 Gy/fraction, (2) irradiated volume constraint of 40-150 cm(3), and (3) uniformity of dose distribution, expressed as the dose non-uniformity ratio (DNR, V150/V100) < 0.35. The ISBT-APBI plan for each patient was considered reproducible when all three criteria were met. When the number of non-reproducible patients was ≤ 4 at study completion, APBI at this institution was considered statistically reproducible. RESULTS: Half of the patients (52 %) had a small bra size (A/B cup). The mean values of the dose-constrained parameters were as follows: Vref, 117 cm(3) (range, 40-282), DNR, 0.30 (range, 0.22-0.51), and clip dose, 784 cGy (range, 469-3146). A total of 43/46 treatment plans were judged to be compliant and ISBT-APBI was concluded to be reproducible. CONCLUSIONS: This study showed that multi-institutional ISBT-APBI treatment plan was reproducible for small breast patient with closed cavity.

A comparison of the respiratory signals acquired by different respiratory monitoring systems used in respiratory gated radiotherapy.

PURPOSE: Respiratory monitoring systems are used to detect the respiratory phase of patients during the planning and administration of respiratory gated radiotherapy by using four-dimensional computed tomography (4DCT) or 4D positron-emission tomography/CT (4DPET/CT) and the linear accelerator (linac), respectively. Generally, identical respiratory monitoring systems are used for 4DCT, 4DPET/CT, and linac. However, different systems are sometimes used in combination because the accessibility of the respiratory monitoring systems may differ by manufacturer. The combined use of different respiratory monitoring systems in phase-based gating is of concern because the differences in the timing of tags (end-respiration signals algorithmically determined by the respiratory monitoring system), defined by the two systems, may result in phase differences, The purpose of this study is to estimate this difference and evaluate its effect on 4DCT data. METHODS: Ten patients (seven men and three women) with a median age of 75 yr (range: 57-84 yr) were treated by gated stereotactic body radiation therapy between April and December 2009. Two types of respiratory monitoring systems--RPM (Varian Medical Systems) and AZ-733V (Anzai MEDICAL)--were placed on the abdominal surface of the patients, and the respiratory signals were acquired by both systems. The relationship between the amplitude peak and the tag obtained by each respiratory system was analyzed for each patient. Further, the 4DCT images were reconstructed by using the signals obtained from both the RPM and the AZ-733V systems, and the tumor volumes and the tumor centroid positions in the craniocaudal plane were analyzed for each patient. RESULTS: The correlation factor between the respiratory signals from the RPM system and AZ-733V system was 0.990 (range: 0.940-0.994). The amplitude peak of the RPM system corresponded well with that of the AZ-733V system. The median +/- standard deviation of the phase difference for all the patients ranged from -4.3 +/- 7.1% to 3.5 +/- 2.2%. In the case of some patients, differences were noted between the two systems in the estimation of the tumor centroid position and tumor shape. CONCLUSIONS: The estimation of the position of the tumor centroid and tumor shape may vary with the use of different respiratory monitoring systems. This implies that it is preferable to use the same respiratory monitoring system with 4DCT, 4DPET-CT, and linac.

[Changes of edema associated with I-125 prostate brachytherapy].

We have been performing TRUS-guided transperineal prostate brachytherapy with I-125 for prostate-confined adenocarcinoma since October 2003. We examined prostate volume using CT scanning on Day 1, Day 15, and Day 30 in the initial 15 patients, and investigated time-dependent changes of edema associated with I-125 prostate brachytherapy. Prostate volume had increased to 173% of the average on the first day after implantation. Improvements in the swelling of the prostate showed decreases in 30% in the first 2 weeks (Days 1-15) and 12% in the second 2 weeks (Days 15-30). V100 and D 90% showed statistically significant increases of 5.5% and 8.4% in the first 2 weeks after implantation and 2.3% and 5.2% in the second 2 weeks (Days 15-30). We considered one month a suitable time at which to calculate post-planning because V100 and D 90% changed little statistically.

Long-term, irradiation-induced effects on thermoregulation in the skin after thermal stimulation.

PURPOSE: The morphological effect of radiation on the skin has been adequately analyzed, but the functional effect has received little attention. The purpose of this study was to examine the long-term effects of radiation on the skin from the viewpoint of function. MATERIALS AND METHODS: Physiological changes in the irradiated skin of patients who had undergone breast-conserving therapy for the treatment of breast cancer were examined throughout the follow-up period. Thermal stimulation was applied to both breasts, and changes in skin temperature and sweating reactivity of irradiated and non-irradiated skin were measured. RESULTS: From three weeks to the end of radiotherapy, the resting skin temperature of the irradiated region was significantly elevated, while the rate of sweating was lower. More than two years after radiotherapy, the elevated resting skin temperature of the irradiated region had returned to within the range observed for non-irradiated skin, although an abnormally high increase in skin temperature after thermal stimulation continued to be observed for more than two years after radiotherapy. At the same time, sweating after thermal stimulation continued to be suppressed. CONCLUSION: Present observations suggest that functional effects, such as the skin temperature and sweating ability of irradiated skin, persist longer than readily visible morphological changes.