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1.  Transitioning from conventional radiotherapy to intensity-modulated radiotherapy for localized prostate cancer: changing focus from rectal bleeding to detailed quality of life analysis 
Journal of Radiation Research  2014;55(6):1033-1047.
With the advent of modern radiation techniques, we have been able to deliver a higher prescribed radiotherapy dose for localized prostate cancer without severe adverse reactions. We reviewed and analyzed the change of toxicity profiles of external beam radiation therapy (EBRT) from the literature. Late rectal bleeding is the main adverse effect, and an incidence of >20% of Grade ≥2 adverse events was reported for 2D conventional radiotherapy of up to 70 Gy. 3D conformal radiation therapy (3D-CRT) was found to reduce the incidence to ∼10%. Furthermore, intensity-modulated radiation therapy (IMRT) reduced it further to a few percentage points. However, simultaneously, urological toxicities were enhanced by dose escalation using highly precise external radiotherapy. We should pay more attention to detailed quality of life (QOL) analysis, not only with respect to rectal bleeding but also other specific symptoms (such as urinary incontinence and impotence), for two reasons: (i) because of the increasing number of patients aged >80 years, and (ii) because of improved survival with elevated doses of radiotherapy and/or hormonal therapy; age is an important prognostic factor not only for prostate-specific antigen (PSA) control but also for adverse reactions. Those factors shift the main focus of treatment purpose from survival and avoidance of PSA failure to maintaining good QOL, particularly in older patients. In conclusion, the focus of toxicity analysis after radiotherapy for prostate cancer patients is changing from rectal bleeding to total elaborate quality of life assessment.
PMCID: PMC4229926  PMID: 25204643
prostate cancer; radiotherapy; rectal bleeding; incontinence; genitourinary symptom; erectile dysfunction
2.  Radiotherapy treatment planning with contrast-enhanced computed tomography: feasibility of dual-energy virtual unenhanced imaging for improved dose calculations 
In radiotherapy treatment planning, intravenous administration of an iodine-based contrast agent during computed tomography (CT) improves the accuracy of delineating target volumes. However, increased tissue attenuation resulting from the high atomic number of iodine may result in erroneous dose calculations because the contrast agent is absent during the actual procedure. The purpose of this proof-of-concept study was to present a novel framework to improve the accuracy of dose calculations using dual-energy virtual unenhanced CT in the presence of an iodine-based contrast agent.
Simple phantom experiments were designed to assess the feasibility of the proposed concept. By utilizing a “second-generation” dual-source CT scanner equipped with a tin filter for improved spectral separation, four CT datasets were obtained using both a water phantom and an iodine phantom: “true unenhanced” images with attenuation values of 2 ± 11 Hounsfield Units (HU), “enhanced” images with attenuation values of 274 ± 23 HU, and two series of “virtual unenhanced” images synthesized from dual-energy scans of the iodine phantom, each with a different combination of tube voltages. Two series of virtual unenhanced images demonstrated attenuation values of 12 ± 29 HU (with 80 kVp/140 kVp) and 34 ± 10 HU (with 100 kVp/140 kVp) after removing the iodine component from the contrast-enhanced images. Dose distributions of the single photon beams calculated from the enhanced images and two series of virtual unenhanced images were compared to those from true unenhanced images as a reference.
The dose distributions obtained from both series of virtual unenhanced images were almost equivalent to that from the true unenhanced images, whereas the dose distribution obtained from the enhanced images indicated increased beam attenuation caused by the high attenuation characteristics of iodine. Compared to the reference dose distribution from the true unenhanced images, the dose distribution pass rates from both series of virtual unenhanced images were greater than 90%, while those from the enhanced images were less than approximately 50–60%.
Dual-energy virtual unenhanced CT improves the accuracy of dose distributions in radiotherapy treatment planning by removing the iodine component from contrast-enhanced images.
PMCID: PMC4118618  PMID: 25070169
Radiotherapy treatment planning; Dual-energy CT; Virtual unenhanced CT; Dose calculation; Iodine contrast agent; Tissue attenuation; CT number; Dual-source CT; Tin filter
3.  Development and reproducibility evaluation of a Monte Carlo-based standard LINAC model for quality assurance of multi-institutional clinical trials 
Journal of Radiation Research  2014;55(6):1131-1140.
Technical developments in radiotherapy (RT) have created a need for systematic quality assurance (QA) to ensure that clinical institutions deliver prescribed radiation doses consistent with the requirements of clinical protocols. For QA, an ideal dose verification system should be independent of the treatment-planning system (TPS). This paper describes the development and reproducibility evaluation of a Monte Carlo (MC)-based standard LINAC model as a preliminary requirement for independent verification of dose distributions. The BEAMnrc MC code is used for characterization of the 6-, 10- and 15-MV photon beams for a wide range of field sizes. The modeling of the LINAC head components is based on the specifications provided by the manufacturer. MC dose distributions are tuned to match Varian Golden Beam Data (GBD). For reproducibility evaluation, calculated beam data is compared with beam data measured at individual institutions. For all energies and field sizes, the MC and GBD agreed to within 1.0% for percentage depth doses (PDDs), 1.5% for beam profiles and 1.2% for total scatter factors (Scps.). Reproducibility evaluation showed that the maximum average local differences were 1.3% and 2.5% for PDDs and beam profiles, respectively. MC and institutions' mean Scps agreed to within 2.0%. An MC-based standard LINAC model developed to independently verify dose distributions for QA of multi-institutional clinical trials and routine clinical practice has proven to be highly accurate and reproducible and can thus help ensure that prescribed doses delivered are consistent with the requirements of clinical protocols.
PMCID: PMC4229916  PMID: 24957755
Monte Carlo; quality assurance; LINAC model; commissioning; multi-institutional clinical trials; dose verification
4.  Evaluation of imaging performance of megavoltage cone-beam CT over an extended period 
Journal of Radiation Research  2013;55(1):191-199.
A linear accelerator vendor and the AAPM TG-142 report propose that quality assurance testing for image-guided devices such megavoltage cone-beam CT (MV-CBCT) be conducted on a monthly basis. In clinical settings, however, unpredictable errors such as image artifacts can occur even when quality assurance results performed at this frequency are within tolerance limits. Here, we evaluated the imaging performance of MV-CBCT on a weekly basis for ∼ 1 year using a Siemens ONCOR machine with a 6-MV X-ray and an image-quality phantom. Image acquisition was undertaken using 15 monitor units. Geometric distortion was evaluated with beads evenly distributed in the phantom, and the results were compared with the expected position in three dimensions. Image-quality characteristics of the system were measured and assessed qualitatively and quantitatively, including image noise and uniformity, low-contrast resolution, high-contrast resolution and spatial resolution. All evaluations were performed 100 times each. For geometric distortion, deviation between the measured and expected values was within the tolerance limit of 2 mm. However, a subtle systematic error was found which meant that the phantom was rotated slightly in a clockwise manner, possibly due to geometry calibration of the MV-CBCT system. Regarding image noise and uniformity, two incidents over tolerance occurred in 100 measurements. This phenomenon disappeared after dose calibration of beam output for MV-CBCT. In contrast, all results for low-contrast resolution, high-contrast resolution and spatial resolution were within their respective tolerances.
PMCID: PMC3885132  PMID: 23979076
Cone-beam CT; QA; image-guided radiation therapy; IGRT; tolerance; calibration
5.  Feasibility and accuracy of relative electron density determined by virtual monochromatic CT value subtraction at two different energies using the gemstone spectral imaging 
Recent work by Saito (2012) has demonstrated a simple conversion from energy-subtracted computed tomography (CT) values (ΔHU) obtained using dual-energy CT to relative electron density (RED) via a single linear relationship. The purpose of this study was to investigate the feasibility of this method to obtain RED from virtual monochromatic CT images obtained by the gemstone spectral imaging (GSI) mode with fast-kVp switching.
A tissue characterization phantom with 13 inserts made of different materials was scanned using the GSI mode on a Discovery CT750 HD. Four sets of virtual monochromatic CT images (60, 77, 100 and 140 keV) were obtained from a single GSI acquisition. When we define Δ HU in terms of the weighting factor for the subtraction α, Δ HU ≡ (1 + α)H - αL (H and L represent the CT values for high and low energy respectively), the relationship between Δ HU and RED is approximated as a linear function, a × Δ HU/1000 + b (a, b = unity). We evaluated the agreement between the determined and nominal RED. We also have investigated reproducibility over short and long time periods.
For the 13 insert materials, the RED determined by monochromatic CT images agreed with the nominal values within 1.1% and the coefficient of determination for this calculation formula was greater than 0.999. The observed reproducibility (1 standard deviation) of calculation error was within 0.5% for all materials.
These findings indicate that virtual monochromatic CT scans at two different energies using GSI mode can provide an accurate method for estimating RED.
PMCID: PMC3627631  PMID: 23570343
Gemstone spectral imaging; Monochromatic images; Relative electron density; Dual energy; Computed tomography
6.  High dose rate brachytherapy for oral cancer 
Journal of Radiation Research  2012;54(1):1-17.
Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer.
PMCID: PMC3534285  PMID: 23179377
brachytherapy; oral cancer; high dose rate
7.  The usefulness of an independent patient-specific treatment planning verification method using a benchmark plan in high-dose-rate intracavitary brachytherapy for carcinoma of the uterine cervix 
Journal of Radiation Research  2012;53(6):936-944.
To develop an easy independent patient-specific quality assurance (QA) method using a benchmark plan for high-dose-rate intracavitary brachytherapy for cervix cancer, we conducted benchmark treatment planning with various sizes and combinations of tandem-ovoid and tandem-cylinder applications with ‘ideal’ geometry outside the patient. Two-dimensional-based treatment planning was conducted based on the Manchester method. We predicted the total dwell time of individual treatment plans from the air kerma strength, total dwell time and prescription dose of the benchmark plan. In addition, we recorded the height (dh), width (dw) and thickness (dt) covered with 100% isodose line. These parameters were compared with 169 and 29 clinical cases for tandem-ovoid or tandem-cylinder cases, respectively. With regard to tandem-ovoid cases, differences in total dwell time, dh, dt and dw between benchmark and individual plans were on average –0.2% ± 3.8%, –1.0 mm ± 2.6 mm, 0.8 mm ± 1.3 mm and –0.1 mm ± 1.5 mm, respectively. With regard to tandem-cylinder cases, differences in total dwell time, dhfront (the distance from tandem tip to tandem ring), dt and dw between benchmark and individual plans were on average –1.5% ± 3.1%, –1.5 mm ± 4.9 mm, 0.1 mm ± 1.0 mm and 0.2 mm ± 0.8 mm, respectively. Of two cases, more than 13% differences in total dwell time were observed between benchmark plans and the clinical cases, which turned out to be due to the use of the wrong source position setting. These results suggest that our method is easy and useful for independent verification of patient-specific treatment planning QA.
PMCID: PMC3483840  PMID: 22843371
independent verification; treatment planning; Manchester method; benchmark plan; high-dose-rate intracavitary brachytherapy; uterine cervix
8.  Quality assurance of MLC leaf position accuracy and relative dose effect at the MLC abutment region using an electronic portal imaging device 
Journal of Radiation Research  2012;53(5):798-806.
We investigated an electronic portal image device (EPID)-based method to see whether it provides effective and accurate relative dose measurement at abutment leaves in terms of positional errors of the multi-leaf collimator (MLC) leaf position. A Siemens ONCOR machine was used. For the garden fence test, a rectangular field (0.2 × 20 cm) was sequentially irradiated 11 times at 2-cm intervals. Deviations from planned leaf positions were calculated. For the nongap test, relative doses at the MLC abutment region were evaluated by sequential irradiation of a rectangular field (2 × 20 cm) 10 times with a MLC separation of 2 cm without a leaf gap. The integral signal in a region of interest was set to position A (between leaves) and B (neighbor of A). A pixel value at position B was used as background and the pixel ratio (A/B × 100) was calculated. Both tests were performed at four gantry angles (0, 90, 180 and 270°) four times over 1 month. For the nongap test the difference in pixel ratio between the first and last period was calculated. Regarding results, average deviations from planned positions with the garden fence test were within 0.5 mm at all gantry angles, and at gantry angles of 90 and 270° tended to decrease gradually over the month. For the nongap test, pixel ratio tended to increase gradually in all leaves, leading to a decrease in relative doses at abutment regions. This phenomenon was affected by both gravity arising from the gantry angle, and the hardware-associated contraction of field size with this type of machine.
PMCID: PMC3430416  PMID: 22843372
MLC; IMRT; EPID; garden fence test; calibration
9.  Japanese structure survey of radiation oncology in 2009 based on institutional stratification of the Patterns of Care Study 
Journal of Radiation Research  2012;53(5):710-721.
The ongoing structure of radiation oncology in Japan in terms of equipment, personnel, patient load and geographic distribution was evaluated in order to radiation identify and improve any deficiencies. A questionnaire-based national structure survey was conducted from March 2010 to January 2011 by the Japanese Society for Therapeutic Radiology and Oncology (JASTRO). These data were analyzed in terms of the institutional stratification of the Patterns of Care Study (PCS). The total numbers of new cancer patients and total of cancer patients (new and repeat) treated with radiation in 2009 were estimated at 201,000 and 240,000, respectively. The type and numbers of systems in actual use consisted of Linac (816), telecobalt (9), Gamma Knife (46), 60Co remote afterloading system (RALS) (29) and 192Ir RALS systems (130). The Linac systems used dual energy function for 586 (71.8%), 3DCRT for 663 (81.3%) and IMRT for 337 units (41.3%). There were 529 JASTRO-certified radiation oncologists (ROs), 939.4 full-time equivalent (FTE) ROs, 113.1 FTE medical physicists and 1836 FTE radiation therapists. The frequency of interstitial radiation therapy use for prostate and of intensity-modulated radiotherapy increased significantly. PCS stratification can clearly identify the maturity of structures based on their academic nature and caseload. Geographically, the more JASTRO-certified physicians there were in a given area, the more radiation therapy tended to be used for cancer patients. In conclusion, the Japanese structure has clearly improved during the past 19 years in terms of equipment and its use, although a shortage of manpower and variations in maturity disclosed by PCS stratification remained problematic in 2009.
PMCID: PMC3430417  PMID: 22843366
Structure survey; radiotherapy facility; radiotherapy personnel; radiotherapy equipment; caseload
10.  Dose reduction trial from 60 Gy in 10 fractions to 54 Gy in 9 fractions schedule in high-dose-rate interstitial brachytherapy for early oral tongue cancer 
Journal of Radiation Research  2012;53(5):722-726.
To compare the effects of 60 Gy/10 fractions (twice a day) with those of 54 Gy/9 fractions in high-dose-rate interstitial brachytherapy (HDR-ISBT) for early tongue cancer, we performed a matched-pair analysis of patients with early tongue cancer (T1-2N0M0), who were treated with 60 or 54 Gy of radiation between 1996 and 2004. Seventeen patients treated with 54 Gy and 34 matched-pair patients treated with 60 Gy were extracted and analyzed. Local recurrence occurred in two patients in the 54-Gy arm and five patients in the 60-Gy arm. The 2-year local control rates were 88% for both the 54-Gy arm and 60-Gy arm (not significant). The 2-year overall survival rates were 88% in the 60-Gy arm and 82% in the 54-Gy arm. Two-year actuarial complication-free rates were 91% in the 60-Gy arm and 83% in the 54-Gy arm (not significant), respectively. There was no significant association between the total dose and local control rate and late complications. The outcome of 54 Gy/ 9 fractions was similar to that of 60 Gy/ 10 fractions in patients with early tongue cancer.
PMCID: PMC3430427  PMID: 22843365
tongue cancer; brachytherapy; interstitial radiotherapy; high dose rate
11.  Age is not a limiting factor for brachytherapy for carcinoma of the node negative oral tongue in patients aged eighty or older 
To examine the role of brachytherapy for aged patients 80 or more in the trend of rapidly increasing number.
We examined the outcomes for elderly patients with node negative oral tongue cancer (T1-3N0M0) treated with brachytherapy. The 21 patients (2 T1, 14 T2, and 5 T3 cases) ranged in age from 80 to 89 years (median 81), and their cancer was pathologically confirmed. All patients underwent definitive radiation therapy, with low dose rate (LDR) Ra-226 brachytherapy (n = 4; median 70Gy), with Ir-192 (n = 12; 70Gy), with Au-198 (n = 1) or with high dose rate (HDR) Ir-192 brachytherapy (n = 4; 60 Gy). Eight patients also underwent external radiotherapy (median 30 Gy). The period of observation ranged from 13 months to 14 years (median 2.5 years). We selected 226 population matched younger counterpart from our medical chart.
Definitive radiation therapy was completed for all 21 patients (100%), and acute grade 2-3 mucositis related to the therapy was tolerable. Local control (initial complete response) was attained in 19 of 21 patients (90%). The 2-year and 5-year local control rates were 91%, (100% for T1, 83% for T2 and 80% for T3 tumors after 2 years). These figures was not inferior to that of younger counterpart (82% at 5-year, n.s.). The cause-specific survival rate was 83% and the regional control rate 84% at the 2-years follow-up. However, 12 patients died because of intercurrent diseases or senility, resulting in overall survival rates of 55% at 2 years and 34% at 5 years.
Age is not a limiting factor for brachytherapy for appropriately selected elderly patients, and brachytherapy achieved good local control with acceptable morbidity.
PMCID: PMC3016284  PMID: 21143904

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