Kazufumi Kagawa

Initial clinical assessment of CT-MRI image fusion software in localization of the prostate for 3D conformal radiation therapy☆

PURPOSE To assess the utility of image fusion software and compare MRI prostate localization with CT localization in patients undergoing 3D conformal radiation therapy of prostate cancer. MATERIALS AND METHODS After a phantom study was performed to ensure the accuracy of image fusion procedure, 22 prostate cancer patients had CT and MRI studies before the start of radiotherapy. Immobilization casts used during radiation treatment were also used for both imaging studies. After the clinical target volume (CTV) (prostate or prostate + seminal vesicles) was defined on CT, slices from the MRI study were reconstructed to precisely match the CT slices by identifying three common bony landmarks on each study. The CTV was separately defined on the matched MRI slices. Data related to the size and location of the prostate were compared between CT and MRI. The spatial relationship between the tip of urethrogram cone on CT and prostate apex seen on MRI was also estimated. RESULTS The phantom study showed the registration discrepancies between CT and MRI smaller than 1.0 mm in any pair in comparison. The patient study showed a mean image registration error of 0.9 (+/- 0.6) mm. The average prostate volume was 63.0 (+/- 25.8) cm3 and 50.9 (+/- 22.9) cm3 determined by CT and MRI, respectively. The difference in prostate location with the two studies usually differed at the base and at the apex of the prostate. On the transverse MRI, the prostate apex was situated 7.1 (+/- 4.5) mm dorsal and 15.1 (+/- 4.0) mm cephalad to the tip of urethrogram cone. CONCLUSIONS CT-MRI image fusion study made it possible to compare the two modalities directly. MRI localization of the prostate is more accurate than CT, and indicates the distance from cone to apex is 15 mm. CT-MRI image fusion technique provides valuable supplements to CT technology for more precise targeting of the prostate cancer.

Preclinical biological assessment of proton and carbon ion beams at Hyogo Ion Beam Medical Center

PURPOSE To assess the biologic effects of proton and carbon ion beams before clinical use. METHODS AND MATERIALS Cultured cells from human salivary gland cancer (HSG cells) were irradiated at 5 points along a 190 MeV per nucleon proton and a 320 MeV per nucleon carbon ion beam, with Bragg peaks modulated to 6 cm widths. A linac 4 MV X-ray was used as a reference. Relative biologic effectiveness (RBE) values at each point were calculated from survival curves. Cells were also irradiated in a cell-stack phantom to identify that localized cell deaths were observed at predefined depth. Total body irradiation of C3H/He mice was performed, and the number of regenerating crypts per jejunal section was compared to calculate intestinal RBE values. For carbon ion and referential 4 MV X-ray beams, mouse right legs were irradiated by four-fractional treatment and followed up for skin reaction scoring. RESULTS RBE values calculated from cell survival curves at the dose that would reduce cell survival to 10% (D10) ranged from 1.01 to 1.05 for protons and from 1.23 to 2.56 for carbon ions. The cell-stack phantom irradiation revealed localized cell deaths at predefined depth. The intestinal RBE values ranged from 1.01 to 1.08 for protons and from 1.15 to 1.88 for carbon ions. The skin RBE value was 2.16 at C320/6 cm spread-out Bragg peak (SOBP) center. CONCLUSION The radiobiologic measurements of proton and carbon ion beams at Hyogo Ion Beam Medical Center are consistent with previous reports using proton beams in clinical settings and carbon ion beams with similar linear energy transfer (LET) values.

Usefulness of positron-emission tomographic images after proton therapy ☆

PURPOSE To examine the positron emission tomography (PET) image obtained after proton irradiation and investigate the usefulness of the image for confirmation of the irradiated volume in proton radiotherapy (RT). METHODS AND MATERIALS A homogenous phantom was irradiated separately by carbon-ion and proton beams and the images obtained were compared. The PET images of cancer patients just after proton RT were then taken after informed consent. RESULTS In the PET image produced by carbon-ion beams, the high pixel counts in the image corresponded to the Bragg peak; however, in that produced by proton beams, they were visible throughout the entire track of the proton beams and were not related to the Bragg peak. The PET image of patients treated with proton RT was similar to that of the phantom experiment. CONCLUSION The PET image after proton RT was different from that of carbon-ion RT. It was found that the PET image was very useful in proton RT to verify treatment planning.

Status of the clinical work at Hyogo

On April 1, 2001, the Hyogo Ion Beam Medical Center (HIBMC) was opened as the first facility in the world to provide ion beam therapy using 2 types of beams, protons and carbon-ions. We will introduce the HIBMC, and report the results of the clinical study and general practice.

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.

External-Beam Radiotherapy for Clinically LocalizedProstate Cancer in Osaka, Japan, 1995–2006

Purpose:To establish an initial database of external-beam radiotherapy (EBRT) for clinically localized prostate cancer used in Osaka, Japan, and, by analyzing the results of the Osaka multicenter cooperative study, to determine time trends, outcome, and applicability of existing and the authors’ original risk stratification methods.Patients and Methods:Data of 652 patients with clinically localized prostate cancer (T1–4 N0 M0) were accrued from July to December 2007. These patients had been treated from 1995 through 2006 with consecutive definitive EBRT of ≥ 60 Gy at eleven institutions, mainly in Osaka. Altogether, 436 patients were eligible for analysis using several risk stratification methods, namely, those of D’Amico et al., the National Comprehensive Cancer Network (NCCN), and Seattle, as well as the authors’ original Prostate Cancer Risk Index (PRIX).Results:The number of patients showed a tenfold increase over 10 years, together with a rapid spread of the use of Gleason Score from 0% to > 90% of cases. The dominant RT dose fractionation was 70 Gy/35 fractions (87%). Hormone therapy had been administered to 95% of the patients and the higher PRIX corresponded to the higher rate of hormone usage. 3- and 5-year biochemical relapse-free survival (bRFS) rates were 85% and 70%, respectively. The D’Amico (p = 0.132), NCCN (p = 0.138), Seattle (p = 0.041) and PRIX (p = 0.044) classifications showed weak or no correlation with bRFS, while the own modified three-class PRIX (PRIX 0, 1–5, 6) showed a strong correlation (p = 0.002).Conclusion:The use of prostate EBRT in Japan is still in its infancy, but is rapidly expanding. The short-term outcomes have been satisfactory considering the moderate RT dose. A very high rate of hormone usage may affect the outcome favorably, but also may compromise the usefulness of current risk stratification.Ziel:Erstellung einer ersten Datenbank zur perkutanen Strahlentherapie (EBRT) bei klinisch lokalisiertem Prostatakrebs in Osaka, Japan, und Ermittlung der zeitlichen Entwicklung, Resultate und Anwendbarkeit der existierenden und der eigenen Risikostratifikationsmethoden mittels Analyse der Ergebnisse der multizentrischen kooperativen Osaka-Studie.Patienten und Methodik:Daten von 652 Patienten mit klinisch lokalisiertem Prostatakrebs (T1–4 N0 M0) wurden von Juli bis Dezember 2007 erfasst. Diese Patienten waren zwischen 1995 und 2006 in elf Einrichtungen, vorwiegend in Osaka, mit konsekutiver definitiver EBRT von ≥ 60 Gy behandelt worden. Insgesamt 436 Patienten qualifizierten sich für die Analyse mittels mehrerer Risikostratifikationsmethoden, namentlich jener von D’Amico et al., National Comprehensive Cancer Network (NCCN) und Seattle sowie des eigenen Prostatakrebsrisikoindex (PRIX).Ergebnisse:Die Anzahl der Patienten stieg binnen 10 Jahren um das Zehnfache, und gleichzeitig kam es zu einem rasch zunehmenden Einsatz des Gleason-Scores von 0% auf > 90% der Fälle. Die dominante RT-Dosisfraktionierung betrug 70 Gy/35 Frak tionen (87%). Eine Hormontherapie war 95% der Patienten verabreicht worden, und der höhere PRIX entsprach der höheren Rate des Hormoneinsatzes. Die 3- und 5-Jahres-Raten des biochemisch rezidivfreien Überlebens (bRFS) lagen bei 85% bzw. 70%. Die Klassifikationen von D’Amico et al. (p = 0,132), NCCN (p = 0,138), Seattle (p = 0,041) und PRIX (p = 0,044) zeigten eine schwache Korrelation mit dem bRFS, wogegen der eigene modifizierte Drei-Klassen-PRIX (PRIX 0, 1–5, 6) eine starke Korrrelation (p = 0,002) ergab.Schlussfolgerung:Der Einsatz der Prostata-EBRT in Japan ist noch in der Anfangsphase begriffen, breitet sich aber rasch aus. Angesichts moderater RT-Dosen sind zufriedenstellende kurzfristige Resultate erzielt worden. Eine sehr hohe Rate von Hormonverabreichungen mag die Ergebnisse günstig beeinflussen, könnte aber auch die Nützlichkeit der gegenwärtigen Risikostratifikation gefährden.

External-beam radiotherapy for clinically localized prostate cancer in Osaka, Japan, 1995-2006: time trends, outcome, and risk stratification.

Purpose:To establish an initial database of external-beam radiotherapy (EBRT) for clinically localized prostate cancer used in Osaka, Japan, and, by analyzing the results of the Osaka multicenter cooperative study, to determine time trends, outcome, and applicability of existing and the authors’ original risk stratification methods.Patients and Methods:Data of 652 patients with clinically localized prostate cancer (T1–4 N0 M0) were accrued from July to December 2007. These patients had been treated from 1995 through 2006 with consecutive definitive EBRT of ≥ 60 Gy at eleven institutions, mainly in Osaka. Altogether, 436 patients were eligible for analysis using several risk stratification methods, namely, those of D’Amico et al., the National Comprehensive Cancer Network (NCCN), and Seattle, as well as the authors’ original Prostate Cancer Risk Index (PRIX).Results:The number of patients showed a tenfold increase over 10 years, together with a rapid spread of the use of Gleason Score from 0% to > 90% of cases. The dominant RT dose fractionation was 70 Gy/35 fractions (87%). Hormone therapy had been administered to 95% of the patients and the higher PRIX corresponded to the higher rate of hormone usage. 3- and 5-year biochemical relapse-free survival (bRFS) rates were 85% and 70%, respectively. The D’Amico (p = 0.132), NCCN (p = 0.138), Seattle (p = 0.041) and PRIX (p = 0.044) classifications showed weak or no correlation with bRFS, while the own modified three-class PRIX (PRIX 0, 1–5, 6) showed a strong correlation (p = 0.002).Conclusion:The use of prostate EBRT in Japan is still in its infancy, but is rapidly expanding. The short-term outcomes have been satisfactory considering the moderate RT dose. A very high rate of hormone usage may affect the outcome favorably, but also may compromise the usefulness of current risk stratification.Ziel:Erstellung einer ersten Datenbank zur perkutanen Strahlentherapie (EBRT) bei klinisch lokalisiertem Prostatakrebs in Osaka, Japan, und Ermittlung der zeitlichen Entwicklung, Resultate und Anwendbarkeit der existierenden und der eigenen Risikostratifikationsmethoden mittels Analyse der Ergebnisse der multizentrischen kooperativen Osaka-Studie.Patienten und Methodik:Daten von 652 Patienten mit klinisch lokalisiertem Prostatakrebs (T1–4 N0 M0) wurden von Juli bis Dezember 2007 erfasst. Diese Patienten waren zwischen 1995 und 2006 in elf Einrichtungen, vorwiegend in Osaka, mit konsekutiver definitiver EBRT von ≥ 60 Gy behandelt worden. Insgesamt 436 Patienten qualifizierten sich für die Analyse mittels mehrerer Risikostratifikationsmethoden, namentlich jener von D’Amico et al., National Comprehensive Cancer Network (NCCN) und Seattle sowie des eigenen Prostatakrebsrisikoindex (PRIX).Ergebnisse:Die Anzahl der Patienten stieg binnen 10 Jahren um das Zehnfache, und gleichzeitig kam es zu einem rasch zunehmenden Einsatz des Gleason-Scores von 0% auf > 90% der Fälle. Die dominante RT-Dosisfraktionierung betrug 70 Gy/35 Frak tionen (87%). Eine Hormontherapie war 95% der Patienten verabreicht worden, und der höhere PRIX entsprach der höheren Rate des Hormoneinsatzes. Die 3- und 5-Jahres-Raten des biochemisch rezidivfreien Überlebens (bRFS) lagen bei 85% bzw. 70%. Die Klassifikationen von D’Amico et al. (p = 0,132), NCCN (p = 0,138), Seattle (p = 0,041) und PRIX (p = 0,044) zeigten eine schwache Korrelation mit dem bRFS, wogegen der eigene modifizierte Drei-Klassen-PRIX (PRIX 0, 1–5, 6) eine starke Korrrelation (p = 0,002) ergab.Schlussfolgerung:Der Einsatz der Prostata-EBRT in Japan ist noch in der Anfangsphase begriffen, breitet sich aber rasch aus. Angesichts moderater RT-Dosen sind zufriedenstellende kurzfristige Resultate erzielt worden. Eine sehr hohe Rate von Hormonverabreichungen mag die Ergebnisse günstig beeinflussen, könnte aber auch die Nützlichkeit der gegenwärtigen Risikostratifikation gefährden.

Relative biological effectiveness of therapeutic proton beams for HSG cells at Japanese proton therapy facilities

We investigated the relative biological effectiveness (RBE) of therapeutic proton beams at six proton facilities in Japan with respect to cell lethality of HSG cells. The RBE of treatments could be determined from experimental data. For this purpose, we used a cell survival assay to compare the cell-killing efficiency of proton beams. Among the five linear accelerator (LINAC) X-ray machines at 4 or 6 MeV that were used as reference beams, there was only a small variation (coefficient of variation CV = 3.1% at D10) in biological effectiveness. The averaged value of D10 for the proton beams at the middle position of the spread-out Bragg peak (SOBP) was 4.98. These values showed good agreement, with a CV of 4.3% among the facilities. Thus, the average RBE10 (RBE at the D10 level) at the middle position of the SOBP beam for six facilities in Japan was 1.05 with a CV of 2.8%.

Focal Residual Contrast Media in the Kidney 24 Hours after Angiography

Purpose: To examine the relationship between focal renal cortical retention (FRCR) and contrast-associated nephropathy (CAN). Material and Methods: We investigated the incidence of both phenomena in 105 patients. CAN was defined as an increase in the creatinine level >0.3 mg/dl and >20% on days 1, 3, or 7. We compared predisposing factors for FRCR and CAN. Serum creatinine and blood urea nitrogen (BUN) for renal function were determined on the morning of the day of the angiography. The BUN/creatinine ratio was used as an indicator of the degree of hydration. Results: FRCR was demonstrated in 17 patients (16%) by delayed CT 24 h after angiography, and CAN was found in 16 patients (15%). No significant relationship between CAN and FRCR was found. We found a correlation between high total volumes of contrast and FRCR. Advanced age, high blood urea nitrogen, high creatinine, and dehydration were risk factors for CAN. Conclusion: Delayed CT showed a higher incidence of injury to the renal parenchyma than previously detected by conventional radiography.

External-Beam Radiotherapy for Clinically Localized Prostate Cancer in Osaka, Japan, 1995–2006@@@Perkutane Strahlentherapie bei klinisch lokalisiertem Prostatakrebs in Osaka, Japan, 1995–2006. Zeitliche Entwicklung, Resultate und Risikostratifikation: Time Trends, Outcome, and Risk Stratification

Purpose:To establish an initial database of external-beam radiotherapy (EBRT) for clinically localized prostate cancer used in Osaka, Japan, and, by analyzing the results of the Osaka multicenter cooperative study, to determine time trends, outcome, and applicability of existing and the authors’ original risk stratification methods.Patients and Methods:Data of 652 patients with clinically localized prostate cancer (T1–4 N0 M0) were accrued from July to December 2007. These patients had been treated from 1995 through 2006 with consecutive definitive EBRT of ≥ 60 Gy at eleven institutions, mainly in Osaka. Altogether, 436 patients were eligible for analysis using several risk stratification methods, namely, those of D’Amico et al., the National Comprehensive Cancer Network (NCCN), and Seattle, as well as the authors’ original Prostate Cancer Risk Index (PRIX).Results:The number of patients showed a tenfold increase over 10 years, together with a rapid spread of the use of Gleason Score from 0% to > 90% of cases. The dominant RT dose fractionation was 70 Gy/35 fractions (87%). Hormone therapy had been administered to 95% of the patients and the higher PRIX corresponded to the higher rate of hormone usage. 3- and 5-year biochemical relapse-free survival (bRFS) rates were 85% and 70%, respectively. The D’Amico (p = 0.132), NCCN (p = 0.138), Seattle (p = 0.041) and PRIX (p = 0.044) classifications showed weak or no correlation with bRFS, while the own modified three-class PRIX (PRIX 0, 1–5, 6) showed a strong correlation (p = 0.002).Conclusion:The use of prostate EBRT in Japan is still in its infancy, but is rapidly expanding. The short-term outcomes have been satisfactory considering the moderate RT dose. A very high rate of hormone usage may affect the outcome favorably, but also may compromise the usefulness of current risk stratification.Ziel:Erstellung einer ersten Datenbank zur perkutanen Strahlentherapie (EBRT) bei klinisch lokalisiertem Prostatakrebs in Osaka, Japan, und Ermittlung der zeitlichen Entwicklung, Resultate und Anwendbarkeit der existierenden und der eigenen Risikostratifikationsmethoden mittels Analyse der Ergebnisse der multizentrischen kooperativen Osaka-Studie.Patienten und Methodik:Daten von 652 Patienten mit klinisch lokalisiertem Prostatakrebs (T1–4 N0 M0) wurden von Juli bis Dezember 2007 erfasst. Diese Patienten waren zwischen 1995 und 2006 in elf Einrichtungen, vorwiegend in Osaka, mit konsekutiver definitiver EBRT von ≥ 60 Gy behandelt worden. Insgesamt 436 Patienten qualifizierten sich für die Analyse mittels mehrerer Risikostratifikationsmethoden, namentlich jener von D’Amico et al., National Comprehensive Cancer Network (NCCN) und Seattle sowie des eigenen Prostatakrebsrisikoindex (PRIX).Ergebnisse:Die Anzahl der Patienten stieg binnen 10 Jahren um das Zehnfache, und gleichzeitig kam es zu einem rasch zunehmenden Einsatz des Gleason-Scores von 0% auf > 90% der Fälle. Die dominante RT-Dosisfraktionierung betrug 70 Gy/35 Frak tionen (87%). Eine Hormontherapie war 95% der Patienten verabreicht worden, und der höhere PRIX entsprach der höheren Rate des Hormoneinsatzes. Die 3- und 5-Jahres-Raten des biochemisch rezidivfreien Überlebens (bRFS) lagen bei 85% bzw. 70%. Die Klassifikationen von D’Amico et al. (p = 0,132), NCCN (p = 0,138), Seattle (p = 0,041) und PRIX (p = 0,044) zeigten eine schwache Korrelation mit dem bRFS, wogegen der eigene modifizierte Drei-Klassen-PRIX (PRIX 0, 1–5, 6) eine starke Korrrelation (p = 0,002) ergab.Schlussfolgerung:Der Einsatz der Prostata-EBRT in Japan ist noch in der Anfangsphase begriffen, breitet sich aber rasch aus. Angesichts moderater RT-Dosen sind zufriedenstellende kurzfristige Resultate erzielt worden. Eine sehr hohe Rate von Hormonverabreichungen mag die Ergebnisse günstig beeinflussen, könnte aber auch die Nützlichkeit der gegenwärtigen Risikostratifikation gefährden.