Yoshiyuki Hiraki

Variation of Clinical Target Volume Definition among Japanese Radiation Oncologists in External Beam Radiotherapy for Prostate Cancer

BACKGROUND We investigated the interobserver variation in the prostate target volume and the trend toward the use of diagnostic computed tomography (CT) or magnetic resonance (MR) images for treatment planning. METHODS Twenty-five radiation oncologists were asked to draw the external contour of the prostate on CT images (0.3 cm spacing) of a patient with localized prostate cancer. They also answered a questionnaire regarding the use of diagnostic CT or MR images for the contouring. RESULTS Of the 25 physicians, 28% rarely or never referred to the diagnostic CT images. In contrast, the physicians tended to refer to the MR images more frequently. Approximately 50% of the physicians believed in the usefulness of contrast-enhanced images for the delineation of the prostate. As for the variation of the prostate contouring, the median craniocaudal prostate length was 36 mm (range, 21-54 mm), and the median prostate volume was 43.5 cm(3) (range, 23.8-98.3 cm(3)). The interobserver variability was not significant in the duration as a radiation oncologist, the board certification status as radiation oncologists, and the number of treatment plans developed for prostate cancer during the last 1 year. CONCLUSION A wide variety of the definitions of the prostate was found among Japanese radiation oncologists.

Sclerosing hemangioma of the lung : MR findings and correlation with pathological features

Two sclerosing hemangiomas of the lung had mixed areas of high and low signal intensity on both T1- and T2-weighted images and were totally enhanced on postcontrast T1-weighted images. The T1 high signal intensity areas corresponded to those including abundant clear cells, and the T2-weighted low signal intensity areas corresponded to the fibrotic or hemorrhagic areas in the tumors. The T2 high signal intensity areas with remarkable contrast enhancement corresponded to the hemangiomatous parts of the tumors.

A multicentre randomised clinical trial of chemoradiotherapy plus hyperthermia versus chemoradiotherapy alone in patients with locally advanced cervical cancer

Abstract Purpose: To evaluate the effectiveness of whole-pelvic hyperthermia (HT) added to standard chemoradiotherapy (CRT) in locally advanced cervical cancer (CC), by investigating the clinical response and survival of patients treated with cisplatin-based CRT vs. CRT with HT (CRT + HT). Materials and methods: This study was conducted at five hospitals in Japan between September 2001 and March 2015 in patients with the International Federation of Gynecology and Obstetrics stage IB (bulky)–IVA CC undergoing definitive CRT. After giving a written informed consent, patients were randomly allocated to two treatment groups: CRT and CRT + HT group. Overall survival (OS), disease-free survival (DFS), local relapse-free survival (LRFS), complete response (CR) rate and tolerability were evaluated. Results: In total, 101 patients were treated. Patient characteristics, total dose of cisplatin and radiotherapy were similar for both groups. Although not statistically significant, the 5-year OS, DFS and LRFS in the CRT + HT group (77.8%, 70.8% and 80.1%, respectively) were better than those in the CRT group (64.8%, 60.6% and 71.0%, respectively). CR was significantly more likely to be achieved in patients in the CRT + HT group than in the CRT group (88% vs. 77.6%; adjusted odds ratio, 3.993; 95% confidence interval, 1.018–15.67; p = .047). CRT + HT was well tolerated and caused no additional acute or long-term toxicity compared with CRT alone. Conclusions: HT combined with CRT improved the CR rate of CRT in patients with locally advanced CC, however, could not improve survival outcomes. Further studies in larger samples are warranted.

Improvement in treatment results of glioblastoma over the last three decades and beneficial factors

Abstract Background. The purpose of this study is to elucidate the trend of glioblastoma outcome and scrutinize the factors contributing to better outcome over three decades. Methods. Survival time and the influencing factors were retrospectively analyzed in 223 newly diagnosed primary glioblastoma patients during 1980–2010. Appraised factors included age, sex, tumor site, year of surgery, extent of resections, use of surgery supporting system, Karnofsky Performance Status (KPS), chemotherapy, conventional external beam radiotherapy (EBRT), and CyberKnife stereotactic radiotherapy (CK-SRT) use. Results. The median survival time (MST) in all patients was 13.6 months. The MSTs for 4 periods were 9.8 (1980–1990), 13.7 (1991–2000), 12.9 (2001–2005), and 15.8 months (2006–2010), respectively (p = 0.0047). Total resection, subtotal resection, partial resection, and biopsy had MSTs of 31.8, 13.9, 11.4, and 7.0 months, respectively (p < 0.0001). Regarding chemotherapy, MSTs of the temozolomide base group and nimustine hydrochloride (ACNU) base group were 16.9 and 14.6 months, respectively, whereas the MST of patients without chemotherapy was only 9.8 months (p < 0.0001). The MSTs for 40-Gy EBRT plus CK-SRT and 60-Gy EBRT were 19.1 and 10.7 months, respectively (p < 0.0001). But in sub-selected patients, treated during 2001–2010, whose resection rate was total resection or subtotal resection, EBRT was completed and postoperative KPS was greater than or equal to 70, the MST with and without CK-SRT was 26.6 and 18.3 months, respectively (p = 0.1529). According to the Cox proportional hazards model, degree of resection, KPS, ACNU use, temozolomide use, bevacizumab use, EBRT dose, and CK-SRT use were good prognostic factors. Use of neuronavigation and use of intraoperative magnetic resonance imaging were related to higher resection rate, but not determined as prognostic factors. Conclusions. We observed a gradual improvement in glioblastoma outcome, presumably because of improvements in therapeutic modalities for surgery, anticancer agents, and radiation, but the efficacy of CK-SRT remains unclear.

Long-term survivors of advanced esophageal cancer without surgical treatment: a multicenter questionnaire survey in Kyushu, Japan

SUMMARY Since the introduction of recent improvements in adjuvant therapy for esophageal cancer, some patients have demonstrated good prognosis. In the present study, we analyzed 3- and 5-year survivors of advanced esophageal cancer who did not undergo any surgical treatment. Between 1990 and 1998, 831 patients were admitted to 14 university hospitals and one cancer center associated with the membership of the Kyushu study group for adjuvant therapy of esophageal cancer. Twelve (1.4%) of the patients were 3-year survivors and 13 (1.6%) were 5-year survivors. The reasons for non-operation were refusal (eight patients), tumor-related factors (11 patients), and host-related factors (six patients). With a single exception, all patients had locally advanced tumors. Almost all long-term survivors had fewer than five lymph node metastases, in regions limited to the neck and/or mediastinum. Radiation therapy was combined with chemotherapy for 16 of the 25 patients, and chemotherapy-based cisplatin was used for 15 of these 16 patients. Fifteen of the patients remain alive; 10 died seven of them from esophageal cancer. Chemoradiation therapy was effective for some patients with locally advanced esophageal cancer, particularly in the absence of or with few lymph node metastases. To improve the prognosis of patients with advanced esophageal cancer who, for various causes, cannot undergo surgical treatment, a new protocol for adjuvant therapy is required.

Effectiveness of RF capacitive hyperthermia combined with radiotherapy for stages III and IV oro-hypopharyngeal cancers: a non-randomized comparison between thermoradiotherapy and radiotherapy.

Seventy-two patients with Stages III and IV (TNM, UICC, 1987) squamous-cell carcinoma of the oropharynx and hypopharynx (oro-hypopharyngeal cancer) were treated with external irradiation, or irradiation plus 13.56 MHz radiofrequency (RF) capacitive hyperthermia from 1989 to 1995. This study compared initial response, histological effect and 5-year survival rate of thermoradiotherapy (TRT) group with those of radiotherapy alone (RT) group. In the TRT group, 15 patients were treated definitively, and 18 patients preoperatively. In the RT group, 15 patients were treated definitively, and 24 patients preoperatively. With definitive irradiation, the complete response rate of the primary lesions was 73% in the TRT group and 27% in the RT group (p = 0.009) and the complete response rate of the metastatic lymph nodes was 80% in the TRT group and 27% in the RT group (p = 0.005). With preoperative irradiation, the pathological CR (No residual cancerous cells) rate of the primary lesions was 56% in the TRT group and 8% in the RT group (p = 0.01), and the pathological CR rate of the lymph nodes was 72% in the TRT group and 21% in the RT group (p = 0.001). The 5-year survival rates with definitive irradiation were 47.6% in the TRT group and 18.7% in the RT group (p = 0.025). Thus TRT was more effective than RT for advanced oro-hypopharyngeal cancer.

The position of the opposite flat applicator changes the SAR and thermal distributions of the RF capacitive intracavitary hyperthermia.

The variations of the specific absorption rate (SAR) and thermal distribution in the JSHO QA phantoms were investigated by radiofrequency (RF) capacitive intracavitary hyperthermia (ICHT) applicator (AP-T01, Omron Electric Co., Kyoto, Japan) with the changing position of the opposite flat applicator (15-cm in diameter). The thermal distribution was observed with the thermographic camera and the normalized SAR distribution was calculated with the thermal data that were measured with the thermocouple thermometers. The SAR and thermal distributions of AP-T01 significantly varied with the position of the opposite flat applicator. The slope of the normalized SAR became gradual towards the side of the flat applicator. During the operating of a high flow rate (1500ml/min) cooling system, the region between AP-T01 and the flat applicator was widely and rather homogeneously heated, except the hot spot around the end of AP-T01. This hot spot may be due to the imbalance of cooling of AP-T01 and the warming-up of the electrode. These results suggest that the RF capacitive ICHT using AP-T01 may be clinically effective on the deep-seated tumours in the direction of either the end wall, such as cervical cancers, or the upper wall, such as prostatic cancers and the mediastinal metastatic lymph nodes, if an improvement of the cooling system is achieved.

Increased accumulation of iodine-123-IMP in the pulmonary inflammatory lesion surrounding a lung cancer

In a patient with primary lung cancer, increased accumulation of I-123-IMP was observed in a pulmonary inflammatory lesion surrounding a lung cancer which was delineated as a photon deficient area. Ga-67-citrate uptake was observed in both the inflammatory and cancerous areas. These findings suggest that I-123-IMP may have the potential to accumulate differently in a variety of pathological conditions of the lung and thus may be a clinically useful lung imaging agent.

Relationships between thermal dose parameters and the efficacy of definitive chemoradiotherapy plus regional hyperthermia in the treatment of locally advanced cervical cancer: data from a multicentre randomised clinical trial

Abstract Purpose: To evaluate the contribution of the thermal dose parameters during regional hyperthermia (HT) treatment to the clinical outcomes in patients with cervical carcinoma (CC) who received chemoradiotherapy (CRT) plus HT. Materials and methods: Data from a multicentre randomised clinical trial of concurrent CRT + HT vs. CRT alone were used to evaluate the efficacy and safety of this combination therapy in the CC patients. The intrarectal temperatures of patients undergoing HT were recorded. The complete thermal data of 47 (92%) of the 51 patients in the CRT + HT group were available for the thermal analysis. Thus, 47 patients who received CRT + HT were included in the present study. Results: Among the patients who received CRT + HT, a higher CEM43T90 (≥1 min) value (a thermal dose parameter) was significantly associated with better local relapse-free survival in both univariate (p = 0.024) and multivariate (p = 0.0097) analyses. The disease-free survival of the patients with higher CEM43T90 (≥1 min) values tended to be better in comparison to patients with lower CEM43T90 (<1 min) value (p = 0.071). A complete response tended to be associated with the CEM43T90 (p = 0.056). Disease-free survival, local relapse-free survival and complete response rate for patients with higher CEM43T90 (≥1) were significantly better than those for patients with CRT alone (p = 0.036, p = 0.036 and p = 0.048). Conclusions: Dose-effect relationships between thermal dose parameters and clinical outcomes were confirmed in the CC patients treated with a combination of CRT + HT. This study also confirmed that HT with lower CEM43T90 is insufficient to achieve a significant hyperthermic sensitisation to CRT.

The size and distance of the opposite flat applicator change the SAR and thermal distributions of RF capacitive intracavitary hyperthermia.

The variations of the specific absorption rate (SAR) and thermal distributions in the JSHO QA phantom were investigated by using the radiofrequency (RF) capacitive intracavitary hyperthermia (ICHT) applicator (AP-T01, Omron Electric Co., Kyoto, Japan) and the opposite flat applicators of different sizes (AP-75E: 7.5cm in diameter, AP-100E: 10cm in diameter, and AP-150E: 15cm in diameter). The influences of the distance between both applicators were also investigated. Heating of the region between both applicators became weaker with the increase in size of the opposite flat applicator, and it became stronger with the decrease of the distance between both applicators. Heating near the flat applicator became weaker with the increase in size of the flat applicators, and it showed no apparent difference with the increase of the distance between both applicators. The normalized SAR values between AP-T01 and the opposite flat applicator became smaller and its slope became steeper with the increase in size of the opposite flat applicator and in the distance between both applicators. These results suggest that the variability of the specific absorption rate (SAR) and thermal distributions of the region between both applicators may show the potentiality of usefulness for heating the tumours of various sizes, shapes and location.