Hideya Yamazaki

Phase III trial of high- vs. low-dose-rate interstitial radiotherapy for early mobile tongue cancer.

PURPOSE Oral tongue carcinomas are highly curable with radiotherapy. In the past, patients with tongue carcinoma have usually been treated with low dose rate (LDR) interstitial radiation. This Phase III study was designed to compare the treatment results obtained with LDR with those obtained with high dose rate (HDR) interstitial radiotherapy for tongue carcinoma. METHODS AND MATERIALS The criteria for patient selection for the Phase III study were: (a) presence of a T1T2N0 tumor that could be treated with single-plane implantation, (b) localization of tumor at the lateral tongue border, (c) tumor thickness of 10 mm or less, (d) performance status between O and 3, and (e) absence of any severe concurrent disease. From April 1992 through December 1993, 15 patients in the LDR group (70 Gy/4 to 9 days) and 14 patients in the HDR group (60 Gy/10 fractions/6 days) were accrued. The time interval between two fractions of the HDR brachytherapy was more than 6 h. RESULTS Local recurrence occurred in two patients treated with LDR brachytherapy but in none of the patients treated with HDR. One- and 2-year local control rates for patients in the LDR group were both 86%, compared with 100% in the HDR group (p = 0.157). There were four patients with nodal metastasis in the LDR group and three in the HDR group. Local recurrence occurred in two of the four patients with nodal metastases in the LDR group. One- and 2-year nodal control rates for patients in the LDR group are were 85%, compared with 79% in the HDR group. CONCLUSION HDR fractionated interstitial brachytherapy can be an alternative to traditional LDR brachytherapy for early tongue cancer and eliminate the radiation exposure for medical staffs.

High-dose-rate brachytherapy as monotherapy for localized prostate cancer: A retrospective analysis with special focus on tolerance and chronic toxicity

PURPOSE To examine retrospectively fractionated high-dose-rate brachytherapy as monotherapy for localized prostate cancer with special focus on tolerance and toxicity, especially chronic toxicity. MATERIALS AND METHODS Between May 1995 and October 2001, 43 patients with localized prostate cancer were treated with high-dose-rate brachytherapy without external beam irradiation at Osaka University Hospital. The stage was T1, T2, T3, and T4 in 8, 14, 18, and 3 patients, respectively. The adenocarcinoma was well, moderately, or poorly differentiated in 12, 16, and 15 patients, respectively. The median initial prostate-specific antigen level was 19.3 ng/mL (range 3.8-233.0). Thirty-eight patients also received hormonal therapy. Metallic needles were implanted transperineally under real-time ultrasound guidance, followed by a dose optimization program. Patients were irradiated twice daily at intervals of >6 h. A total dose of 54 Gy in nine fractions within 5 days (48 Gy in eight fractions within 5 days for the first 7 cases) was administered in one implant session. The median follow-up was 24 months (range 1-76). RESULTS Radiation Therapy Oncology Group acute toxicity of Grade 4, 2, and 1 occurred in 1 (2%), 12 (28%), and 8 (19%) patients, respectively. Five patients had late toxicity: one with rectal ulcer (Grade 2) and four with rectal bleeding (Grade 1). The volume receiving 100% of the prescribed dose showed significant correlations with the incidence of acute and chronic toxicities (p = 0.005 and p = 0.014, respectively). The 3-year actuarial overall survival, local control, and biochemical no evidence of disease rate was 94%, 100%, and 55%, respectively. The crude biochemical control rate for low, intermediate, and high-risk patients was 100% (5 of 5), 80% (8 of 10), and 61% (17 of 28), respectively. CONCLUSIONS High-dose-rate brachytherapy as monotherapy was found to be feasible and well tolerated. It showed a low chronic toxicity rate without any event of Radiation Therapy Oncology Group of Grade 3 or greater.

Results of low- and high-dose-rate interstitial brachytherapy for T3 mobile tongue cancer

PURPOSE To evaluate the treatment results of low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy (ISBT) for T3 mobile tongue cancer. MATERIAL AND METHODS Between 1974 and 1992, 61 patients with T3 mobile tongue cancer were treated with LDR ISBT using (192)Ir hairpins with or without single pins. In addition, between 1991 and 1999, 14 patients were treated with HDR ISBT. For nine patients treated with ISBT alone, the total dose was 59-94 Gy (median 72 Gy) within one week in LDR ISBT and 60 Gy/10 fractions/5 days in HDR ISBT. For 66 patients treated with a combination therapy of external beam radiotherapy (EBRT) and ISBT, the total dose was 12.5-60 Gy (median 30 Gy) of EBRT and 50-112 Gy (median 68 Gy) within 1 week in LDR ISBT or 32-60 Gy (median 48 Gy)/8-10 fractions/5-7 days in HDR ISBT. RESULTS The 2- and 3-year local control rates of all patients were both 68%. The 2- and 3-year local control rates of patients treated with LDR ISBT were both 67%, and those with HDR ISBT were both 71%. The local control rate of patients treated with HDR ISBT was similar to those with LDR ISBT. CONCLUSIONS ISBT for T3 mobile tongue cancer is effective and acceptable. The treatment result of HDR ISBT is almost similar to that of LDR ISBT for T3 mobile tongue cancer.

LYMPH NODE METASTASIS OF EARLY ORAL TONGUE CANCER AFTER INTERSTITIAL RADIOTHERAPY

PURPOSE To examine the prognostic factors for lymph node metastasis after brachytherapy for early (T1-T2N0M0) oral tongue cancer. METHODS AND MATERIALS We reviewed the records of 571 patients (500 low dose rate and 71 high dose rate) treated at Osaka University Hospital between 1967 and 1999. RESULTS Patients with lymph node metastasis had tumor with an average diameter of 26 +/- 8 mm and a thickness of 9 +/- 5 mm; for patients without lymph node metastasis, the corresponding dimensions were 23 +/- 8 mm and 7.5 +/- 4 mm (p = 0.0004 and 0.001, respectively). After 5 years, the ulcerative (48%) and indurative/infiltrative (39%) types showed a higher ratio of nodal involvement than the exophytic (31%) and superficial (19%) types (p <0.0001). Multivariate analysis showed ulceration (p = 0.006) and a thickness of <or =6 mm (p = 0.04) to be statistically significant predisposing factors for lymph node metastasis. The lymph node control rate was 68% in 1967-1979, 71% in 1980-1990, and 66% in 1990-1999; the corresponding successful salvage rates for lymph node metastasis were 43%, 33%, and 58% (p = 0.04). CONCLUSION The appearance of the tumor, especially the presence or absence of ulceration and the diameter and thickness, are useful prognostic indicators for lymph node metastasis. Although the rates of lymph node metastasis did not change, the salvage outcome for recurrence after interstitial radiotherapy has recently improved.

High dose rate versus low dose rate interstitial radiotherapy for carcinoma of the floor of mouth

PURPOSE Patients with cancer of the floor of mouth are treated with radiation because of functional and cosmetic reasons. We evaluate the treatment results of high dose rate (HDR) and low dose rate (LDR) interstitial radiation for cancer of the floor of mouth. METHODS AND MATERIALS From January 1980 through March 1996, 41 patients with cancer of the floor of mouth were treated with LDR interstitial radiation using 198Au grains, and from April 1992 through March 1996 16 patients with HDR interstitial radiation. There were 26 T1 tumors, 30 T2 tumors, and 1 T3 tumor. For 21 patients treated with interstitial radiation alone, a total radiation dose of interstitial therapy was 60 Gy/10 fractions/6-7 days in HDR and 85 Gy within 1 week in LDR. For 36 patients treated with a combination therapy, a total dose of 30 to 40 Gy of external radiation and a total dose of 48 Gy/8 fractions/5-6 days in HDR or 65 Gy within 1 week in LDR were delivered. RESULTS Two- and 5-year local control rates of patients treated with HDR interstitial radiation were 94% and 94%, and those with LDR were 75% and 69%, respectively. Local control rate of patients treated with HDR brachytherapy was slightly higher than that with 198Au grains (p = 0.113). For late complication, bone exposure or ulcer occurred in 6 of 16 (38%) patients treated with HDR and 13 of 41 (32%) patients treated with LDR. CONCLUSION HDR fractionated interstitial brachytherapy can be an alternative to LDR brachytherapy for cancer of the floor of mouth and eliminate radiation exposure for the medical staff.

Radiotherapy of early tongue cancer in patients less than 40 years old

PURPOSE To evaluate the results of treatment for early mobile tongue cancer in patients less than 40 years. METHODS AND MATERIALS Between January 1967 and September 1992, 70 patients less than 40 years old (young age group) with early tongue cancer (T1-2N0M0) were treated with low-dose-rate (LDR) interstitial radiotherapy at the Osaka University Hospital (OUH). All patients had a minimum 2-year follow-up (median: 13 years). External radiotherapy (median: 30 Gy) was combined in 25 cases. The treatment results were compared with those for two older age groups (middle age: 40-64 years old; old age: 65 years old or more). RESULTS The 5-year probability of cause-specific survival (CSS) rate for the young age group was 80%, which was not significantly different from the two older groups: 81% for middle age and 71% for old age. However, male patients of young age showed significantly worse rates than those of middle and old age (p = 0.02). The 5-year local control rate for the young age group was 78%. It was not significantly different from the two older groups: 81% for middle age and 70% for old age. The incidence of regional lymph node metastasis was 32% for T1, 48% for T2, 56% for males, and 24% for females. The regional failure rate of young males was significantly higher than those of the two older groups: 32% for middle and 22% for old age (p = 0.001). CONCLUSION The overall treatment results for patients with early tongue cancer less than 40 years old were not worse than those of older age groups. However, male gender was a risk factor for lymph node metastasis and CSS.

Influence of age on the results of brachytherapy for early tongue cancer

PURPOSE To determine the influence of elder age on the results of brachytherapy for early (T1-2 N0 M0) oral tongue cancer and examine the compatibility of low-dose rate (LDR) with high-dose rate (HDR) brachytherapy. METHODS AND MATERIALS We analyzed 591 patients treated at Osaka University Hospital between 1967 and 1999. We compared the results of radiotherapy for 156 elderly patients (137 LDR and 19 HDR) 65 years of age or older and 435 patients (383 LDR and 52 HDR) less than 65 years of age. RESULTS HDR brachytherapy showed the same local control rate as LDR brachytherapy (81% at 3 years). Elderly patients showed a poorer local control rate (75% at 3 years) than the younger group (83% at 3 years)(p = 0.002). Multivariate analysis identified age as the only prognostic factor for local control (p = 0.002). CONCLUSIONS HDR brachytherapy achieved the same result as LDR brachytherapy. However, the elderly patient showed a higher rate of local recurrence after brachytherapy.

Comparative analysis of G2 arrest after irradiation with 75 keV carbon-ion beams and 137Cs γ-rays in a human lymphoblastoid cell line

Heavy-ion beams are more effective than gamma-rays in causing G2 arrest. In this study, we investigated the expression of Wee1 and Cdc2 protein levels in order to analyze the G2 arrest caused by carbon-ion beam irradiation. Human lymphoblastoid TK6 cells were exposed to a 75 keV carbon-ion beam or 137Cs gamma-rays. Although the levels of Wee1 and Cdc2 protein were increased after exposure to either beam, Wee1 protein levels were influenced more by carbon-ion beam irradiation than by gamma-rays. To the contrary, Cdc2 protein levels were increased more by gamma-rays than by carbon-ion beams. These findings suggest that the G2 arrest produced by heavy-ion beams, such as the carbon-ion irradiation used in this study, might be associated with the overexpression of the Wee1 protein and of Cdc2 phosphorylation regulated by Wee1. Together, these events may act to prolong the length of G2 arrest.

HDR and MDR intracavitary treatment for carcinoma of the uterine cervix

AimTreatment of carcinoma of the uterine cervix by remote afterloading brachytherapy has been accompanied with new isotopes having dose rates different from the classical low-dose rate (LDR) radium source. The dose rate conversion factor from LDR to high-dose rate (HDR) found to be around 0.54 in most studies. As regards medium-dose rate (MDR) brachytherapy, the published data are very few and the experience is still short. In this study the experience of Osaka University Hospital with micro-HDR-Selectron and Selectron-MDR, as a preliminary report of the clinical trial, is presented.Patients and MethodFrom August 1991 through April 1993, a total of 45 patients with carcinoma of the uterine cervix were randomly allocated to either microSelectron-HDR or Selectron-MDR at the Osaka University Hospital. As regards HDR, dose to point A was adjusted to 32 Gy (for stages I and II), 30 Gy/4 fractions, and 22.5 Gy/3 fractions, for stages III, and IV, respectively. The corresponding values in case of MDR were 35.6, 34 Gy/4 fractions, and 25.5 Gy/3 fractions. External irradiation, according to the stage, was the same in the 2 groups. Nucletron Planning System (NPS) was used for pre-treatment dose calculation at point A, rectal and bladder wall. The dose rate at point A ranged from 24 to 75.6 cGy/min for the HDR group, while for the MDR group ranged among 174.8 to 229.6 cGy/h.ResultsThe 3-year survival and loco-regional control rates for both modalities were nearly equivalent (62% and 67% for HDR and 68% and 74% for MDR). The cumulative rectal and bladder complication rates were the same in both groups (29% at 3 years), with only 1 patient (MDR-group) developed grade 3 rectal and bladder complication. In this study, point A dose rate correction factor from LDR to HDR was 0.53 and 0.6 from LDR to MDR.ConclusionFrom the previous reports from Osaka University Medical School, as well as others, HDR was proposed as an alternative to LDR brachytherapy for treatment of carcinoma of the uterine cervix. In this report, Selectron-MDR was nearly equivalent to the microSelectron-HDR as regards survival and loco-regional control rates as well as radiation-induced complication. This is a preliminary report, and the study still needs larger number of patients, and longer follow-up period.ZusammenfassungZielDie Therapie des Zervixkarzinoms mittels Afterloading-Brachytherapie wird neuerdings mit neuen Isotopen durchgeführt, die andere Dosisraten haben als die klassischen LDR-Radiumquellen. Der Konversionsfaktor der Dosisrate vom LDR-zum HDR-Verfahren wurde in den meisten Studien mit 0,54 angegeben. Bezogen auf die MDR-Brachytherapie, sind die veröffentlichten Daten spärlich und der klinische Erfahrungshorizont kurz. In dieser Studie werden die klinischen Erfahrungen der Osaka Universitätsklinik mit dem HDR-microSelectron und MDR-Selectron vorgestellt.Patienten und MethodeVon August 1991 bis April 1993 wurden insgesamt 45 Patientinnen mit Zervixkarzinom randomisiert für eine microSelectron-HDR-oder Selectron-MDR-Brachytherapie. Für die HDR-Brachytherapie wurde die Dosis am Punkt A mit 32 Gy in vier Fraktionen (Stadium I und II), 30 Gy in vier Fraktionen (Stadium III) und 22,5 Gy in drei Fraktionen (Stadium IV) festgelegt. Die entsprechenden Werte lagen bei der MDR-Brachytherapie bei 35,6 Gy und 34 Gy in vier Fraktionen bzw. 25,5 Gy in drei Fraktionen. Die extreme Radiotherapie war in Anpassung an das Stadium für beide Gruppen gleich. Das Nucletron-Planungssystem (NPS) wurde für die Kalkulation der Vorbestrahlungsdosis am Punkt A sowie an der Rektum-und Blasenwand verwendet. Die Dosisrate am Punkt A variierte von 24 bis 75,6 cGy/min bei der HDR-Gruppe und zwischen 174,8 und 229,6 cGy/h bei der MDR-Gruppe.ErgebnisseDie Drei-Jahres-Überlebensrate sowie lokoregionale Kontrollrate war bei beiden Bestrahlungsgruppen gleich (62% und 67% bei HDR; 68% und 74% bei MDR). Die kumulativen Komplikationsraten für Rektum und Blase waren ebenfalls gleich (29%); nur ein Patient (MDR-Gruppe) entwickelte Grad-3-Komplikationen an Blase und Rektum. In dieser Studie betrug der Punkt-A-Dosis-Korrekturfaktor von LDR nach HDR 0,53 und von LDR nach MDR 0,6.SchlußfolgerungAusgehend von früheren Berichten der Osaka Universitätsklinik sowie anderen Berichten, wurde die HDR-Brachytherapie als Alternative zur LDR-Brachytherapie bei der Behandlung des Zervixkarzinoms vorgeschlagen. Im vorliegenden Bericht zeigten sich nahezu äquivalente Überlebens-und lokoregionale Komplikationsraten sowie strahlenbedingte Komplikationen für das Selectron-MDR-und das microSelectron-HDR-Verfahren. Dieser vorläufige Bericht wird jedoch noch größere Patientenzahlen und eine längere Nachbeobachtungszeit bis zur endgültigen Beurteilung benötigen.

Lack of correlation between gallbladder opacification in delayed CT and contrast-associated nephropathy

Abstract The objective of our study was to determine the correlation between gallbladder opacification by delayed CT and contrast-associated nephropathy (CAN). Delayed CT after angiography was performed in 269 patients. Gallbladder opacification was defined when the CT value in gallbladder was more than 30 HU. Positive renal dysfunction was recognized as CAN which defined as an increase in serum creatinine level > 0.3 mg/dl and > 20 % on days 1, 3, or 7. Gallbladder opacification appeared in 154 of 269 (57 %) patients and CAN in 35 (13 %) patients. Of 117 patients without gallbladder opacification, 17 CAN (14 %) were recognized, and of 152 patients with gallbladder opacification, 18 CAN (12 %) were recognized. No significant correlation existed between delayed gallbladder opacification and CAN.