RADIATION DOSE REDUCTION AT LOW TUBE VOLTAGE WITH CORONARY ARTERY BYPASS GRAFT COMPUTED TOMOGRAPHY ANGIOGRAPHY BASED ON THE CONTRAST NOISE RATIO INDEX.

To compare the radiation dose and diagnostic ability of the 100-kVp protocol, based on the contrast noise ratio (CNR) index, during coronary artery bypass graft (CABG) vessels with those of the 120-kVp protocol. For the 120-kVp scans (150 patients), the targeted image level was set at 25 Hounsfield units (HU) (CNR120 = iodine contrast/25 HU). For the 100-kVp scans (150 patients), the targeted noise level was set at 30 HU to obtain the same CNR as in the 120-kVp scans (i.e. using 1.2-fold higher iodine contrast, CNR100 = 1.2 × iodine contrast/(1.2 × 25 HU) = CNR120). We compared the CNRs, radiation doses, detection of CABG vessels and visualisation scores of the scans acquired at 120 and 100 kVp, respectively. At the same CNR, the 100-kVp protocol may help reduce the radiation dose by ⁓30% compared with the 120-kVp protocol, without degradation of diagnostic ability during CABG.

COMPARISON OF THE 64- AND 80-DETECTOR ROW COMPUTED TOMOGRAPHY AMONG THE CT NUMBER AND RADIATION DOSE DURING LOWER EXTREMITY COMPUTED TOMOGRAPHY ANGIOGRAPHY.

To compare the computed tomography (CT) number and the radiation dose between the 64 (group A) and 80-detector row (group B) during lower extremity computed tomography angiography (LE-CTA). We enrolled 144 patients underwent LE-CTA and compared the CT number for the popliteal arteries, radiation dose and the rate of the optimal CT number during the LE-CTA exceeding 200 HU between the two groups. The CT number for the popliteal arteries and mean dose-length product was significantly higher in Group A than in Group B (P < 0.01). The rate of the optimal CT number for the popliteal arteries was 23.6% with Group B scanner and 56.9% with Group A (P < 0.05). The 64-detector row CT was significantly higher in the CT number for the popliteal arteries, radiation dose and rate of the optimal CT number during the LE-CTA than the 80-detector row. Depiction ability did not improve by using a high CT scanner with a wider detector during LE-CTA.

Usefulness of the patient-specific contrast enhancement optimizer simulation software during the whole-body computed tomography angiography.

To evaluate whether the patient-specific contrast enhancement optimizer simulation software (p-COP) is useful for predicting contrast enhancement during whole-body computed tomography angiography (WBCTA). We randomly divided the patients into two groups using a random number table. We used the contrast material (CM) injection protocol selected by p-COP in group A (n = 52). The p-COP used an algorithm including data on the individual patient's cardiac output. Group B (n = 50) was assigned to the conventional CM injection protocol based on body weight. We compared the CT number in the abdominal aorta at the celiac artery level between the two groups and classified them as acceptable (> 280 HU) and unacceptable (< 279 HU) based on the optimal CT number for the WBCTA scans. To evaluate the difference in both injection protocols, we compared the visual inspection of the images of the artery of Adamkiewicz in both protocols. The CM dosage and injection rate in group A were significantly lower than those in group B (480.8 vs. 501.1 mg I/kg and 3.1 vs. 3.3 ml/s, p < 0.05). The CT number of the abdominal aorta at the celiac level was 382.4 ± 62.3 HU in group A and 363.8 ± 71.3 HU in group B (p = 0.23). CM dosage and injection rate were positively correlated to cardiac output for group A (r = 0.80, p < 0.05) and group B (r = 0.16, p < 0.05). The number of patients with an acceptable CT number was higher in group A [46/6 (86.7%)] than in group B [43/7 (71.4%)], but not significant (p = 0.71). The visualization rate for the Adamkiewicz artery was not significantly different between groups A and B (p = 0.89). The p-COP was useful for predicting contrast enhancement during WBCTA with a lower CM dosage and a lower contrast injection rate than that based on the body weight protocol. In patients with lower cardiac output a reduction in contrast injection rate and CM dosage did not lead to a reduced imaging quality, thus particularly in this group CM dosage can be reduced by p-COP.

Boron neutron capture therapy using cyclotron-based epithermal neutron source and borofalan (10B) for recurrent or locally advanced head and neck cancer (JHN002): An open-label phase II trial.

BACKGROUND AND PURPOSE: Boron neutron capture therapy (BNCT) can be performed without reactors due to development of cyclotron-based epithermal neutron source (C-BENS), which is optimized for treatment for deeper-seated tumors. The purpose of this study was to evaluate efficacy and safety of cyclotron-based BNCT with borofalan (10B) for recurrent or locally advanced head and neck cancer. MATERIALS AND METHODS: In this open-label, phase II JHN002 trial of BNCT using C-BENS with borofalan (10B), patients with recurrent squamous cell carcinoma (R-SCC) or with recurrent/locally advanced non-squamous cell carcinoma (R/LA-nSCC) of the head and neck were intravenously administered 400 mg/kg borofalan (10B), followed by neutron irradiation. The tumor dose was determined passively as the mucosal maximum dose of 12 Gy-Eq. The primary endpoint was the objective response rate (ORR). Post-trial observational JHN002 Look Up study was planned for evaluating locoregional progression-free survival (LRPFS). RESULTS: Eight R-SCC and 13 R/LA-nSCC patients were enrolled. All R-SCC patients had prior radiotherapy with a median dose of 65.5 Gy (range, 59.4-76.0 Gy). The ORR for all patients was 71%, and complete response/partial response were 50%/25% in R-SCC and 8%/62% in R/LA-nSCC. The 2-year overall survival for R-SCC and R/LA-nSCC were 58% and 100%, respectively. The median LRPFS was 11.5 months for R-SCC. Frequently observed adverse events included alopecia (95%), hyperamylasemia (86%), and nausea (81%). CONCLUSION: These data suggest that BNCT using C-BENS with borofalan (10B) is a promising treatment option for patients with R-SCC or R/LA-nSCC of the head and neck.

Long-term outcome of cutaneous melanoma patients treated with boron neutron capture therapy (BNCT).

Our aim was to assess the long-term clinical outcome of boron neutron capture therapy (BNCT) using 10B-para-boronophenylalanine (BPA) as the boron delivery agent for cutaneous melanoma. Eight patients (eight lesions) were treated between October 2003 and April 2014. Their ages ranged from 48 to 86 years at the time of treatment. All of the targets were primary lesions and they were located on the sole or face. No patient had evidence of regional lymph node involvement, distant metastases or an active secondary cancer. The clinical stage was cT1-2N0M0 and performance scores were <2. BNCT was carried out at the Kyoto University Research Reactor (KUR). The patients were irradiated with an epithermal neutron beam between the curative tumor dose and the tolerable skin dose. Eight patients were evaluated and six showed a complete response (CR), while two patients had a partial response (PR). Of the two patients with a PR, one has remained a PR with brown spots persisting for 7.5 years following BNCT. The tumor in the other patient recurred after 6 years at the site of persisting brown macula. The overall control rate (CR + PR without recurrence) for the cohort was 88% (7/8). There have never been any adverse events >Grade 2 for the long follow-up period. Our results suggest that BNCT may be a promising treatment modality in the management of early stage cutaneous melanoma when wide local excision is not feasible.

Pharmacokinetics of 10B-p-boronophenylalanine (BPA) in the blood and tumors in human patients: A critical review with special reference to tumor-to-blood (T/B) ratios using resected tumor samples.

We reviewed 10B concentration kinetics in the blood and tumors in human patients administered with BPA. The 10B concentration in the blood peaked at the end of intravenous infusion of BPA, followed by a biphasic-decreasing curve with half-lives for the first and second components of the curve being 0.7-3.7 and 7.2-12.0 h, respectively. The mean tumor-to-blood (T/B) ratio obtained from resected tumor samples was 3.40 ± 0.83 for melanoma and the ratio ranged from 1.4 to 4.7 for glioblastoma.

Boron neutron capture therapy for head and neck cancer: Relevance of nuclear-cytoplasmic volume ratio and anti-tumor effect. -A preliminary report.

BNCT is a type of particle beam radiation therapy that utilizes an α particle and 7Li nucleus generated when a thermal neutron is captured by a 10B nucleus involved in the boron compound that has been taken up into tumor tissue selectively. In this report, the relevance of N/C ratio of tumor cell and anti-tumor effect for BNCT clinical cases of head and neck cancer were verified. Examination of pre-irradiated tumor histopathological specimens of 9 BNCT treated head and neck cancer patients (4 CR patients, 5 non-CR patients) was performed. The statistically significant difference between the CR group and the non-CR group was examined for the physical dose was multiplied by the absolute biological effectiveness (ABE) value determined from the patient's tumor specific N/C ratio. Analysis showed the mean tumor dose could not distinguish between CR and non-CR groups. However, the ABE dose could clearly distinguish between the CR group and the non-CR group (p = 0.0250). The N/C ratio of tumor cell can influence the anti-tumor effect of BNCT for HNC.

Boron neutron capture therapy for vulvar melanoma and genital extramammary Paget's disease with curative responses.

BACKGROUND: Although the most commonly recommended treatment for melanoma and extramammary Paget's disease (EMPD) of the genital region is wide surgical excision of the lesion, the procedure is highly invasive and can lead to functional and sexual problems. Alternative treatments have been used for local control when wide local excision was not feasible. Here, we describe four patients with genital malignancies who were treated with boron neutron capture therapy (BNCT). METHODS: The four patients included one patient with vulvar melanoma (VM) and three with genital EMPD. They underwent BNCT at the Kyoto University Research Reactor between 2005 and 2014 using para-boronophenylalanine as the boron delivery agent. They were irradiated with an epithermal neutron beam between the curative tumor dose and the tolerable skin/mucosal doses. RESULTS: All patients showed similar tumor and normal tissue responses following BNCT and achieved complete responses within 6 months. The most severe normal tissue response was moderate skin erosion during the first 2 months, which diminished gradually thereafter. Dysuria or contact pain persisted for 2 months and resolved completely by 4 months. CONCLUSIONS: Treating VM and EMPD with BNCT resulted in complete local tumor control. Based on our clinical experience, we conclude that BNCT is a promising treatment for primary VM and EMPD of the genital region. Trial registration numbers UMIN000005124.

Retrospective analysis of definitive radiotherapy for neck node metastasis from unknown primary tumor: Japanese Radiation Oncology Study Group study.

OBJECTIVE: To investigate the optimal treatment method and risk factor of neck node metastasis from unknown primary tumors (NUP) treated by radiotherapy. METHODS: Retrospective case study based on a multi-institutional survey was conducted by the Japanese Radiation Oncology Study Group. Patients pathologically diagnosed as having NUP from 1998 to 2007 were identified. Univariate and multivariate analyses of overall survival (OS), progression free survival (PFS), neck progression free survival (NPFS) and mucosal progression free survival (MPFS) were evaluated. RESULTS: In total, 130 patients with median age of 65 years were included. Nodal stages N1, N2a, N2b and N2c were observed for 10, 26, 43, 12 and 39 patients, respectively. All the patients received radiotherapy (RT) with neck dissection in 60 and with chemotherapy in 67 cases. The median doses to the metastatic nodes, prophylactic neck and prophylactic mucosal sites were 60.0, 50.4 and 50.4 Gy, respectively. The median follow-up period for surviving patients was 42 months. Among 12 patients, occult primary tumors in the neck region developed after radiotherapy. The 5-year OS, PFS, NPFS and MPFS were 58.1%, 42.4%, 47.3% and 54.9%, respectively. Univariate analysis showed that lower N stage (N1-2b), non-bulky node (<6 cm) and negative extracapsular extension (ECE) status were the factors associated with favorable OS, PFS, NPFS and MPFS. Radical surgery proved to be a favorable factor of OS, NPFS and MPFS. On multivariate analysis, lower N stage and negative ECE status were correlated with improved survival. CONCLUSIONS: Lower nodal stage and negative ECE status showed a favorable impact on survival and disease control in patients with NUP treated by radiotherapy.

Efficacy of prophylactic irradiation to the contralateral testis for patients with advanced-stage primary testicular lymphoma: an analysis of outcomes at a single institution.

BACKGROUND: Primary testicular lymphoma (PTL) is a rare, extranodal lymphoma that often relapses in the contralateral testis. We evaluated outcomes in patients with any stage of PTL who had received CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) with rituximab chemotherapy and prophylactic radiotherapy to the contralateral testis. METHODS: We retrospectively identified 15 patients (median age 66 years; range 39-81) diagnosed with diffuse large B-cell PTL in the period 2000-2014. Characteristics and outcomes of these cases were evaluated. RESULTS: All patients received initial orchiectomy followed by CHOP with or without rituximab. Thirteen patients received prophylactic irradiation to the contralateral testis. During follow-up (median 67 months; range 8-190), one patient died of PTL, three died of other disease, and nine were free from relapse. For stage I-II disease, 5-year progression-free and overall survival rates were 80 and 100%, respectively. For stage III-IV PTL, 5-year progression-free and overall survival rates were 50 and 72%, respectively. Notably, no patient developed contralateral testicular involvement after prophylactic irradiation. CONCLUSIONS: The observed outcomes suggest that the combination of (i) CHOP plus rituximab and (ii) radiotherapy for local recurrence prophylaxis is promising for both stage I-II and stage III-IV PTL.

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 phase I/II clinical trial for the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer.

BACKGROUND: This paper describes about a study protocol of phase I/II multicenter prospective clinical trial evaluating the feasibility and efficacy of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced uterine cervical cancer patients. METHODS AND DESIGN: Patients with histologically confirmed FIGO stage IB2, IIA2, IIB, and IIIB uterine cervical carcinoma width of which is larger than 5 cm assessed by MRI will be entered to this clinical trial. Protocol therapy is 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP (40 mg/m(2)), followed by 24 Gy in 4 fractions of HBT and central shield EBRT up to 50-50.4 Gy in 25-28 fractions. Tumor width is assessed again within one week before the first HBT and if the tumor width is larger than 4 cm, patients proceed to the secondary registration. In phase I section, feasibility of this will be investigated. If less than 10 % out of 20 patients experienced greater than grade 3 acute non-hematologic adverse effects, the study proceeds to phase II part. In phase II part a total of 55 patients will be accrued and the efficacy of the HBT will be investigated comparing with historical control data. If the lower margin of 90 % confidence interval of the 2-year pelvic progression-free survival of the HBT trial is higher than 64 %, the HBT is considered to be more effective than conventional ICBT. DISCUSSION: The aim of this study is to demonstrate the feasibility and efficacy of the HBT for locally advanced cervical cancer. This trial will clarify the indication, feasibility, and efficacy of this new technique. TRIAL REGISTRATION: UMIN000019081 ; Registration date: 2015/9/30.

Early clinical experience utilizing scintillator with optical fiber (SOF) detector in clinical boron neutron capture therapy: its issues and solutions.

BACKGROUND: Real-time measurement of thermal neutrons in the tumor region is essential for proper evaluation of the absorbed dose in boron neutron capture therapy (BNCT) treatment. The gold wire activation method has been routinely used to measure the neutron flux distribution in BNCT irradiation, but a real-time measurement using gold wire is not possible. To overcome this issue, the scintillator with optical fiber (SOF) detector has been developed. The purpose of this study is to demonstrate the feasibility of the SOF detector as a real-time thermal neutron monitor in clinical BNCT treatment and also to report issues in the use of SOF detectors in clinical practice and their solutions. MATERIAL AND METHODS: Clinical measurements using the SOF detector were carried out in 16 BNCT clinical trial patients from December 2002 until end of 2006 at the Japanese Atomic Energy Agency (JAEA) and Kyoto University Research Reactor Institute (KURRI). RESULTS: The SOF detector worked effectively as a real-time thermal neutron monitor. The neutron fluence obtained by the gold wire activation method was found to differ from that obtained by the SOF detector. The neutron fluence obtained by the SOF detector was in better agreement with the expected fluence than with gold wire activation. The estimation error for the SOF detector was small in comparison to the gold wire measurement. In addition, real-time monitoring suggested that the neutron flux distribution and intensity at the region of interest (ROI) may vary due to the reactor condition, patient motion and dislocation of the SOF detector. CONCLUSION: Clinical measurements using the SOF detector to measure thermal neutron flux during BNCT confirmed that SOF detectors are effective as a real-time thermal neutron monitor. To minimize the estimation error due to the displacement of the SOF probe during treatment, a loop-type SOF probe was developed.

Development of a wavelength-separated type scintillator with optical fiber (SOF) dosimeter to compensate for the Cerenkov radiation effect.

The scintillator with optical fiber (SOF) dosimeter consists of a miniature scintillator mounted on the tip of an optical fiber. The scintillator of the current SOF dosimeter is a 1-mm diameter hemisphere. For a scintillation dosimeter coupled with an optical fiber, measurement accuracy is influenced by signals due to Cerenkov radiation in the optical fiber. We have implemented a spectral filtering technique for compensating for the Cerenkov radiation effect specifically for our plastic scintillator-based dosimeter, using a wavelength-separated counting method. A dichroic mirror was used for separating input light signals. Individual signal counting was performed for high- and low-wavelength light signals. To confirm the accuracy, measurements with various amounts of Cerenkov radiation were performed by changing the incident direction while keeping the Ir-192 source-to-dosimeter distance constant, resulting in a fluctuation of <5%. Optical fiber bending was also addressed; no bending effect was observed for our wavelength-separated SOF dosimeter.

Docetaxel/ TS-1 with radiation for unresectable squamous cell carcinoma of the esophagus--a phase II trial.

BACKGROUND: We tried a new regimen of docetaxel / TS-1 (tegafur-gimestat-otastat potassium) combined with radiation for squamous cell carcinoma of the esophagus in a phase II trial. PATIENTS AND METHODS: The patients, whose tumor invaded other organs without other organ metastasis, were given TS-1 (60 mg/m2/day) from days 1 to 14, and docetaxel (20-30 mg/m2) on days 1 and 8. They received radiation in 2.0 Gy from days 1 to 21. Patients were given a seven-day rest after the first course, and then were treated with the same regimen from days 28 to 49. RESULTS: Seventeen cases were enrolled in the study. The response rate was 76.4% (13/17). The overall 5-year survival rate was 29.6% (5/17) and median survival time was 15.2 months. Adverse events more than grade 3 occurred in 10 cases. CONCLUSION: This combination therapy may be one of the most effective treatments because of its lower rate of non-hematological adverse events and higher response rate. Three cases also underwent salvage surgery when the tumor recurred, and in one case, chemoradiation to a metastatic nodule on the thoracic wall was added.

BNCT for advanced or recurrent head and neck cancer.

The therapeutic effect of surgery and/or combination of conventional chemoradiotherapy is limited in the patients with recurrent squamous cell carcinoma (SCC) and locally advanced non-squamous cell carcinoma without malignant melanoma (non-SCC) of the head and neck. Currently, clinical trials of BNCT for head and neck cancers are being conducted in some institutes to verify its the effectiveness. BNCT was performed in 10 patients with recurrent SCC, 7 patients with recurrent non-SCC and 3 patients with newly diagnosed non-SCC in our university between October 2003 and September 2007. Eleven patients showed complete remission and 7 patients showed partial remission of irradiated site. The effective rate [(CR+PR)/total cases] was 90%. No severe acute or chronic normal-tissue reactions were observed in any patients. BNCT is effective and safe in the patients with recurrent SCC and locally advanced non-SCC.

Boron neutron capture therapy for advanced salivary gland carcinoma in head and neck.

PURPOSE: Boron neutron capture therapy (BNCT) is among the radiation treatments known to have a selective lethal effect on tumor cells. This study summarizes the tumor responses and the acute and late adverse effects of BNCT in the treatment of patients with both recurrent and newly diagnosed T4 salivary gland carcinoma. METHODS: Two patients with recurrent cancer and 3 with newly diagnosed T4 advanced malignancy were registered between October 2003 and September 2007, with the approval of the medical ethics committees of Kawasaki Medical School and Kyoto University. BNCT was performed, in a single fraction using an epithermal beam, at Japan Research Reactor 4. RESULTS: All patients achieved a complete response within 6 months of treatment. The median duration of the complete response was 24.0 months; the median overall survival time was 32.0 months. Three of the 5 patients are still alive; the other 2 died of distant metastatic disease. Open biopsy of the parotid gland after BNCT was performed in 1 patient and revealed no residual viable cancer cells and no serious damage to the normal glandular system. Although mild alopecia, xerostomia, and fatigue occurred in all patients, there were no severe adverse effects of grade 3 or greater. CONCLUSIONS: Our preliminary results demonstrate that BNCT is a potential curative therapy for patients with salivary gland carcinoma. The treatment does not cause any serious adverse effects, and may be used regardless of whether the primary tumor has been previously treated.

Boron neutron capture therapy outcomes for advanced or recurrent head and neck cancer.

We retrospectively review outcomes of applying boron neutron capture therapy (BNCT) to unresectable advanced or recurrent head and neck cancers. Patients who were treated with BNCT for either local recurrent or newly diagnosed unresectable head or neck cancers between December 2001 and September 2007 were included. Clinicopathological characteristics and clinical outcomes were retrieved from hospital records. Either a combination of borocaptate sodium and boronophenylalanine (BPA) or BPA alone were used as boron compounds. In all the treatment cases, the dose constraint was set to deliver a dose <10-12 Gy-eq to the skin or oral mucosa. There was a patient cohort of 62, with a median follow-up of 18.7 months (range, 0.7-40.8). A total of 87 BNCT procedures were performed. The overall response rate was 58% within 6 months after BNCT. The median survival time was 10.1 months from the time of BNCT. The 1- and 2-year overall survival (OS) rates were 43.1% and 24.2%, respectively. The major acute Grade 3 or 4 toxicities were hyperamylasemia (38.6%), fatigue (6.5%), mucositis/stomatitis (9.7%) and pain (9.7%), all of which were manageable. Three patients died of treatment-related toxicity. Three patients experienced carotid artery hemorrhage, two of whom had coexistent infection of the carotid artery. This study confirmed the feasibility of our dose-estimation method and that controlled trials are warranted.

Long-term outcome of hypofractionated radiotherapy to the whole breast of Japanese women after breast-conserving surgery.

BACKGROUND: In Japan, there are still no reports of long-term outcome for hypofractionated radiotherapy to the whole breast after breast-conserving surgery (BCS). We report our institution's results from evaluation of the efficacy and safety of hypofractionated radiotherapy for Japanese women. METHODS: Data in the medical records of 327 patients were retrospectively reviewed. The patients were treated with hypofractionated radiotherapy between January 2003 and December 2006 at the Kawasaki Medical School Hospital and were followed for more than 3 years. The median age was 54 years old (the age range was 28-80 years). The whole breast was irradiated with a total dose of 42.56 Gy/16 fx with boost irradiation to positive margins. Adjuvant therapy consisted of chemotherapy and/or hormone therapy and was administered to 300 patients, based on their stage or pathological findings. RESULTS: Follow-up periods ranged from 21 to 92 months; the median follow-up period was 60 months. At 5-year follow-up, overall survival, cause-specific survival, relapse-free survival, and local control were 96.0, 97.5, 95.3, and 99.7% respectively. Grade 2 radiation pneumonitis occurred in five patients. Grade 2 radiation dermatitis occurred in 17 patients. Severe late complications were not observed. CONCLUSIONS: In our study, hypofractionated radiotherapy led to good results without severe toxicity. We believe hypofractionated radiotherapy after BCS is safe and efficient treatment for Japanese women.

Alteration of cytoskeletal molecules in a human T cell line caused by continuous exposure to chrysotile asbestos.

Among the various biological effects of asbestos such as fibrogenesis and carcinogenesis, we have been focusing on the immunological effects becausesilica (SiO(2)) and asbestos chemically is a mineral silicate of silica. Observations of the effects of asbestos on CD4+ T cells showed reduction of CXCR3 chemokine receptor and reduced capacity of interferon γ production. In particular, use of theHTLV-1 immortalized human T cell line, MT-2, and cDNA array analysis have helped to identify the modification of CXCR3. We investigated alteration of protein expression among MT-2 original cells that had no contact with asbestos, and six chrysotile-continuously exposed independent sublines using ProteinChip and two-dimensional gel electrophoresis (2DGE) assays. Further confirmation of the changes in protein expression due to asbestos exposure was obtained after the 2DGE method indicated protein modification of ß-actin. ß-actin was upregulated in mRNA, as were the levels of protein expression and phosphorylation. Moreover, a binding assay between cells and chrysotile showed that various molecules related to the cytoskeleton such as vimentin, myosin-9 and tubulin-ß2, as well as ß-actin, exhibited enhanced bindings in asbestos-exposed cells. The overall findings indicate that the cell surface cytoskeleton may play an important role in inducing the cellular changes caused by asbestos in immune cells, since fibers are not incorporated to the cells and how the alterations of cytoskeleton determined cell destiny to cause the reduction of tumor immunity is important to consider the biological effects of asbestos. Further studies to target several cytoskeleton-related molecules associated with the effects of asbestos will result in a better understanding of the immunological effects of asbestos and support the development of chemo-prevention to recover anti-tumor immunity in asbestos-exposed patients.