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.

The Safety and Efficacy of Combination Therapy of Sorafenib and Radiotherapy for Advanced Hepatocellular Carcinoma: A Retrospective Study.

Objective Sorafenib is a standard therapy for advanced hepatocellular carcinoma (HCC), whereas radiotherapy is effective for local control of extrahepatic spread (EHS) or macrovascular invasion (MVI). This study investigated the safety and efficacy of this combined therapy to treat advanced HCC. Methods This retrospective study reviewed 62 patients with advanced-stage HCC with EHS or MVI who received sorafenib therapy, excluding the patients with only lung metastases. Results Of the 62 patients, 15 were treated using the combined therapy of sorafenib and radiotherapy (group RS), and 47 were treated with sorafenib monotherapy (group S). In group RS, patients were treated using three-dimensional conformal radiotherapy with a total irradiation dose of 30-60 Gy (median, 50 Gy). Irradiation was targeted at the bone, lymph nodes, adrenal gland, and MVI in 6, 5, 1, and 4 patients, respectively. The overall incidence of adverse events was 93.3% in group RS and 91.5% in group S (p=N.S.). Incidences of thrombocytopenia, leukopenia, and skin reaction were significantly higher in group RS (73.3%, 40.0%, and 66.7%, respectively) than in group S (36.2%, 10.6%, and 27.7%, respectively, p=0.02, 0.02, and <0.01, respectively). The incidence of severe adverse events, however, was comparable in the 2 groups: 20% in group RS and 19.2% in group S. The median progression-free survival (PFS) of EHS or MVI, PFS of whole lesions, and overall survival were longer in group RS (13.5, 10.6, and 31.2 months, respectively) than in group S (3.3, 3.5, and 12.1 months, respectively) (p<0.01 for all). Conclusion Sorafenib in combination with radiotherapy is a feasible and tolerable treatment option for advanced HCC.

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.

Nationwide multi-institutional retrospective analysis of high-dose-rate brachytherapy combined with external beam radiotherapy for localized prostate cancer: An Asian Prostate HDR-BT Consortium.

PURPOSE: To report outcomes and risk factors of high-dose-rate (HDR) brachytherapy combined with external beam radiotherapy with or without androgen deprivation therapy (ADT) in prostate cancer patients. MATERIALS AND METHODS: This multi-institutional retrospective analysis comprised 3424 patients with localized prostate cancer at 16 Asian hospitals. One-thirds (27.7%) of patients received only neoadjuvant ADT, whereas almost half (49.5%) of patients received both neoadjuvant and adjuvant ADT. Mean duration of neoadjuvant and adjuvant ADT were 8.6 months and 27.9 months, respectively. Biochemical failure was defined by Phoenix ASTRO consensus. Biochemical control rate, clinical disease-free survival (cDFS), cause-specific survival, and overall survival (OS) were calculated. RESULTS: Median followup was 66 months. Ten-year biochemical control, cDFS, cause-specific survival, and OS rate were 81.4%, 81.0%, 97.2%, and 85.6%, respectively. Receiving both neoadjuvant and adjuvant ADT was detected as a favorable factor for biochemical control, cDFS, and OS, but pelvic irradiation was detected as an adverse factor for cause-specific survival, and OS. Ten-year cumulative rates of late Grade ≥2 genitourinary and gastrointestinal toxicities were 26.8% and 4.1%, respectively; receiving both neoadjuvant and adjuvant ADT was detected as a favorable factor for preventing both toxicities. CONCLUSIONS: HDR combined with external beam radiotherapy was an effective and safe treatment for localized prostate cancer. Combination of long-term ADT was suggested to be necessary, even for HDR brachytherapy, and was useful in suppressing late toxicities. Meanwhile, pelvic irradiation was suggested to have an adverse effect on OS of our study population.

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.

Favorable control of rapidly progressive retroperitoneal pleomorphic leiomyosarcoma with multimodality therapy: a case report.

BACKGROUND: Retroperitoneal sarcomas (RPS), such as pleomorphic leiomyosarcoma, often invade or displace vital organs in the abdominal cavity and exhibit an aggressive clinical course. Complete surgical resection of the tumor and preoperative radiotherapy and chemotherapies can be used for non-metastatic RPS. However, in case of huge retroperitoneal sarcoma fully occupying the abdominal cavity, surgical resection tends to be insufficient, resulting in poor outcomes. This report describes a case of rapidly progressive retroperitoneal pleomorphic leiomyosarcoma that was favorably controlled by debulking surgery followed by combination chemotherapy and radiotherapy. CASE PRESENTATION: A 65-year-old Japanese woman developed abdominal discomfort due to a huge retroperitoneal tumor fully occupying the abdominal cavity. The immunohistochemical diagnosis was pleomorphic leiomyosarcoma with high-grade malignancy and aggressive proliferative features. Debulking surgery could be performed, but the small residual tumor had rapidly grown to an approximately 22 cm in length on the major axis within 38 days after the operation. The patient's general condition progressively declined. Combination chemotherapy, consisting of doxorubicin and ifosfamide, was successfully administered for six cycles while maintaining dose intensity. The best objective response was a partial response, and the chemotherapy was well tolerated. Approximately 50 Gy of radiotherapy was delivered to the remaining tumor. This multimodal strategy resulted in progression-free survival for more than 17 months and achieved sustained symptomatic relief. CONCLUSIONS: Multimodal therapy with debulking surgery, combination chemotherapy and radiotherapy controlled a rapidly progressive retroperitoneal pleomorphic leiomyosarcoma. Maintaining dose intensity of the chemotherapy and radiotherapy might contribute to overall tumor control.

[Clinical outcome in prostate cancer patients undergoing high-dose-rate brachytherapy with external beam radiotherapy in our institute].

OBJECTIVES: We investigate the biochemical control rates and adverse events for local and locally advanced prostate cancer patients undergoing high-dose-rate brachytherapy with external beam radiotherapy (EBRT + HDR-BT) in our institute. PATIENTS AND METHODS: From May 2004 through March 2010, 154 patients with local and locally advanced prostate cancer underwent EBRT + HDR-BT. One hundred thirteen patients with more than 6 months follow-up were evaluated. A median follow-up was 33 months. The patients consisted of 12 low-, 65 intermediate- and 36 high-risk patients. No patients received adjuvant androgen deprivation therapy with EBRT + HDR-BT. Biochemical freedom from failure (bFFF) was determined using the Phoenix definition. RESULTS: The 5-year bFFF rate was 100%, 94.7%, and 59.2% for low-, intermediate- and high-risk patients. The 58-month bFFF rate of high-risk patients with one ominous factor was significantly lower than that of high-risk patients with more than ominous two factors (87.4% vs 26.9%, p = 0.022). With respect to acute adverse events, transurethral electric coagulation was performed for vesical bleeding and tamponade after removal of applicator needles in only one patient. Regarding late adverse events 14.2% of patients had grade 3 genitourinary toxicity, mostly consisted of urethral stricture and 0.9% of patients had grade 3 gastrointestinal toxicity. CONCLUSIONS: EBRT + HDR-BT without adjuvant androgen deprivation therapy yields excellent bFFF in low- and intermediate-risk prostate cancer patients. However, to challenge higher bFFF rate in a part of high-risk patients and lower rate of adverse events, modified designing protocols and therapeutic plannning of EBRT + HDR-BT may be necessary.

[High-dose-rate brachytherapy with external beam radiotherapy for localized or locally advanced prostate cancer].

PURPOSE: To evaluate the therapeutic outcomes and late toxicities in patients treated by high-dose-rate brachytherapy (HDR-BT) with external beam radiotherapy (EBRT) for localized or locally advanced prostate cancer. MATERIALS AND METHODS: From May 2004 to September 2008, 86 men were treated by HDR-BT with EBRT for localized or locally advanced prostate cancer at the National Hospital Organization Kyushu Medical center. The median EBRT and HDR-BT doses were 40 Gy and 30 Gy, respectively. RESULT: With a median follow-up of 24 months, the 3-year overall, disease specific, and biochemical relapse-free survival rates in all patients were 97.3%, 100%, and 83.6% respectively. The 3-year biochemical relapse-free survival rate of the patients categorized to low or intermediate risk group (91.8%) was significantly better than that of the patients categorized to the high risk group (74.3%) (p = 0.042). There was no significant difference of biochemical relapse-free survival regarding to the other clinical factors (age, T-stage, Gleason score, initial prostate-specific antigen level, neoadjuvant hormone therapy, and total dose of EBRT and HDR-BT). Late Grade2 and Grade3 gastrointestinal toxicities were observed in 8 patients (9.3%) and 2 patients (2.3%), respectively. Late Grade2 genitourinary toxicities were observed in 12 patients (13.9%). There was no patient suffered from late Grade3 or greater genitourinary toxicities. CONCLUSION: HDR-BT with EBRT can be safe and effective for localized or locally advanced prostate cancer.

Metastatic hepatocellular carcinoma of the external auditory canal.

This report describes a rare case of metastatic hepatocellular carcinoma (HCC) presenting a huge mass in the left external auditory canal (EAC). The patient was a 55-year-old man with hepatitis B virus-related HCC. He presented to our department with a three-month history of increasing left otalgia, and hearing loss with recent fresh aural bleeding. Histopathologic examination indicated that the tumor was secondary to HCC. Although external irradiation was not effective, the tumor was treated with surgical debulking and high dose rate 192 Ir remote afterloading system (RALS) for postoperative intracavitary irradiation. A review of the literature revealed only five other cases of HCC metastasis to the temporal bone, all of which mainly metastasized in the internal acoustic meatus. The present case is the first report of HCC metastasis to the EAC.