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Background: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is defined by p16 positivity and/or HPV DNA positivity. Because survival of patients with HPV-related OPSCC after chemoradiotherapy is favorable, a de-intensified treatment is expected to lead to less morbidity while maintaining low mortality. The association of tumor p16 and HPV DNA status with survival after radiotherapy alone remains unknown., Methods: We retrospectively examined survival of 107 patients with locally advanced OPSCC after radiotherapy alone (n = 43) or chemoradiotherapy (n = 64) with respect to tumor p16 and HPV DNA status, using Cox's proportional hazard model., Results: Survival after radiotherapy alone was significantly worse in p16-positive/HPV DNA-negative locally advanced OPSCC than in p16-positive/HPV DNA-positive locally advanced OPSCC. In bivariable analyses that included T category, N category, TNM stage, and smoking history, the survival disadvantage of p16-positive/HPV DNA-negative locally advanced OPSCC remained significant. There was no significant difference in survival after chemoradiotherapy between p16-positive/HPV DNA-positive locally advanced OPSCC and p16-positive/HPV DNA-negative locally advanced OPSCC. Survival in p16-positive/HPV DNA-positive locally advanced OPSCC after radiotherapy alone was similar to that after chemoradiotherapy, which stayed unchanged in bivariable analyses after adjustment of every other covariable. Survival of p16-negative/HPV DNA-negative locally advanced OPSCC was poor irrespective of treatment modality., Conclusions: Survival in p16-positive locally advanced OPSCC differs depending on HPV DNA status. Radiotherapy alone can serve as a de-intensified treatment for p16-positive/HPV DNA-positive locally advanced OPSCC, but not for p16-positive/HPV DNA-negative locally advanced OPSCC.

The troubles arising in the introduction of the medical information system are mostly related to the requirement definition. The present study proposed the requirements definition method on radiation therapy information system (RTIS) by using business modeling. The interview was conducted with six medical professionals regarding the entire business in the radiotherapy department. These businesses were modeled using Diamond Mandala Matrix (DMM) and data flow diagram (DFD) methods. Subsequently, functional requirements on RTIS were defined based on these modeling. As a result, 21 DMMs and 129 DFDs were created and 120 functional requirements were defined. By defining the functional requirements of the users, mutual understanding with vendors will deepen, and avoid an expected trouble in introducing RTIS. DMM was effective as an initial modeling such as the interviews and the organization of businesses. DFD was also effective for the business improvement and the definition of system functional requirements.

Purpose: Respiratory monitoring systems are used to detect the respiratory phase of patients during the planning and administration of respiratory gated radiotherapy by using four-dimensional computed tomography (4DCT) or 4D positron-emission tomography/CT (4DPET/CT) and the linear accelerator (linac), respectively. Generally, identical respiratory monitoring systems are used for 4DCT, 4DPET/CT, and linac. However, different systems are sometimes used in combination because the accessibility of the respiratory monitoring systems may differ by manufacturer. The combined use of different respiratory monitoring systems in phase-based gating is of concern because the differences in the timing of tags (end-respiration signals algorithmically determined by the respiratory monitoring system), defined by the two systems, may result in phase differences, The purpose of this study is to estimate this difference and evaluate its effect on 4DCT data., Methods: Ten patients (seven men and three women) with a median age of 75 yr (range: 57-84 yr) were treated by gated stereotactic body radiation therapy between April and December 2009. Two types of respiratory monitoring systems--RPM (Varian Medical Systems) and AZ-733V (Anzai MEDICAL)--were placed on the abdominal surface of the patients, and the respiratory signals were acquired by both systems. The relationship between the amplitude peak and the tag obtained by each respiratory system was analyzed for each patient. Further, the 4DCT images were reconstructed by using the signals obtained from both the RPM and the AZ-733V systems, and the tumor volumes and the tumor centroid positions in the craniocaudal plane were analyzed for each patient., Results: The correlation factor between the respiratory signals from the RPM system and AZ-733V system was 0.990 (range: 0.940-0.994). The amplitude peak of the RPM system corresponded well with that of the AZ-733V system. The median +/- standard deviation of the phase difference for all the patients ranged from -4.3 +/- 7.1% to 3.5 +/- 2.2%. In the case of some patients, differences were noted between the two systems in the estimation of the tumor centroid position and tumor shape., Conclusions: The estimation of the position of the tumor centroid and tumor shape may vary with the use of different respiratory monitoring systems. This implies that it is preferable to use the same respiratory monitoring system with 4DCT, 4DPET-CT, and linac.

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 > or = 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.

In fractionated stereotactic radiotherapy (SRT), the accuracy of patient relocation is very important. The Gill-Thomas-Cosman (GTC) re-locatable stereotactic frame is used for patient immobilization. A depth helmet and measuring probe are used to check the stability of the patient's head position relative to the GTC frame. However, displacement error caused by rotation of the patient's head is not considered in the depth-helmet measurement. Consequently, displacement of the isocenter position cannot be confirmed by the measurement obtained from the depth helmet. In this study, we evaluated the precision of reproducibility by comparing measurement values of the depth helmet with the displacement of anatomical position on a CT image. We analyzed 21 setups of 8 patients immobilized for SRT using the GTC frame, between June 2001 and June 2003. The reproducibility of the GTC frame was checked at each treatment by comparing it with the treatment planning position. The average discrepancy of the GTC frame set-up measured by the depth helmet was 0.6 mm, with a standard deviation of 0.3 mm. The result measured by CT was 0.7 mm, with a standard deviation of 0.4 mm. When the error of each measurement point was within 1.0 mm, the accuracy of relocation of the patient could be considered clinically acceptable. Displacement error not considered in the measurement of the depth helmet could be evaluated by using CT.

Background: Quality assurance (QA) of clinical practice is important for any medical specialty. Programs based on the Patterns of Care Study (PCS) have been developed to compare the quality of radiotherapeutic care at individual institutions, with the national average representing the process and outcome of radiotherapy. The feasibility of these programs was analyzed., Methods: Calculation programs for the national average and standard score were developed to evaluate quantitatively the process and outcome of radiotherapy at individual institutions as well as at the national level. The programs were used to evaluate the quality of radiotherapy for 561 esophageal carcinoma patients surveyed in the Japanese PCS., Results: As a representative example of QA measurement, the national average for the 5-year survival rate for these patients in the nonsurgery group was 5%. The regional averages for those in academic and nonacademic institutions were 9% and 1%, respectively (P = 0.0142), showing a significant difference between these two institutional strata. The standard score compared with the national average for institution No.105, for example, was 16.3 (P < 0.0001), with the positive value indicating that the outcome at this institution was significantly higher than the national average. The corresponding figure compared with the regional average was -0.3 (P = 0.7391), with the negative value indicating the outcome is not superior to the regional average of academic institutions., Conclusions: These programs make it possible to compare quantitatively the quality of radiation therapy at individual institutions with the national and regional averages. They should also be useful for nationwide QA projects in radiation oncology as well as in other medical specialities., (Copyright 2002 American Cancer Society.)

Background: Radiation-induced liver damage (RILD) occasionally occurs following carbon-ion radiotherapy (CIRT) for liver tumors, such as hepatocellular carcinoma (HCC), in patients with impaired liver function disease. However, the associated risk factors remain unknown. The present study aimed to determine the risk factors of RILD after CIRT. Methods: We retrospectively analyzed 108 patients with HCC treated with CIRT at the Osaka Heavy Ion Therapy Center between December 2018 and December 2022. RILD was defined as a worsening of two or more points in the Child–Pugh score within 12 months following CIRT. The median age of the patients was 76 years (range 47–95 years), and the median tumor diameter was 41 mm (range 5–160 mm). Based on the pretreatment liver function, 98 and 10 patients were categorized as Child–Pugh class A and B, respectively. We analyzed patients who received a radiation dose of 60 Gy (relative biological effectiveness [RBE]) in four fractions. The median follow-up period was 9.7 months (range 2.3–41.1 months), and RILD was observed in 11 patients (10.1%). Results: Multivariate analysis showed that pretreatment Child–Pugh score B (p = 0.003, hazard ratio [HR] = 6.90) and normal liver volume spared from < 30 Gy RBE (VS30 < 739 cm3) (p = 0.009, HR = 5.22) were significant risk factors for RILD. The one-year cumulative incidences of RILD stratified by Child–Pugh class A or B and VS30 < 739 cm3 or ≥ 739 cm3 were 10.3% or 51.8% and 39.6% or 9.2%, respectively. Conclusion: In conclusion, the pretreatment Child–Pugh score and VS30 of the liver are significant risk factors for RILD following CIRT for HCC. [ABSTRACT FROM AUTHOR]

The purpose of this survey was to examine the status of radiotherapy in Japan based on the cases registered in the Japanese Radiation Oncology Database (JROD), from 2015 to 2021, and to provide basic data to help improve the usefulness of the JROD in the future. The study population consisted of patients who underwent radiotherapy between 2014 and 2020 and did not opt out of the study. The survey item data analyzed in this study were entered into the database at each radiotherapy institution by referring to medical records from the preceding year. Our results show that the number of registered radiotherapy institutions and cases increased by ~50% in 2019 compared to those in 2015 (to 113 institutions and 60 575 cases, respectively). Among the survey item categories, the registration rate was lowest for prognostic information (13.9% on average over the 7-year period). In terms of the Japanese Society for Radiation Oncology disease site, the breast; lung, trachea and mediastinum and urogenital sites accounted for >50% of the total cases. The average survival and mortality rates over the 7-year study period were 67.4 and 17.4%, respectively. The X-ray radiotherapy completion rate exceeded 90% for all years and across all disease categories. 192Ir-based brachytherapy and 223Ra-based radionuclide therapy accounted for an average of 61.9 and 44.6%, respectively, of all corresponding cases over the 7-year period. In conclusion, this survey enables us to infer the actual status of radiotherapy in Japan based on the analysis of relevant nationwide data. [ABSTRACT FROM AUTHOR]

Introduction: Several studies have reported the relation between the imaging dose and secondary cancer risk and have emphasized the need to minimize the additional imaging dose as low as reasonably achievable. The iterative cone-beam computed tomography (iCBCT) algorithm can improve the image quality by utilizing scatter correction and statistical reconstruction. We investigate the use of a novel iCBCT reconstruction algorithm to reduce the patient dose while maintaining low-contrast detectability and registration accuracy. Methods: Catphan and anthropomorphic phantoms were analyzed. All CBCT images were acquired with varying dose levels and reconstructed with a Feldkamp–Davis–Kress algorithm-based CBCT (FDK-CBCT) and iCBCT. The low-contrast detectability was subjectively assessed using a 9-point scale by 4 reviewers and objectively assessed using structure similarity index (SSIM). The soft tissue-based registration error was analyzed for each dose level and reconstruction technique. Results: The results of subjective low-contrast detectability found that the iCBCT acquired at two-thirds of a dose was superior to the FDK-CBCT acquired at a full dose (6.4 vs 5.4). Relative to FDK-CBCT acquired at full dose, SSIM was higher for iCBCT acquired at one-sixth dose in head and head and neck region while equivalent with iCBCT acquired at two-thirds dose in pelvis region. The soft tissue-based registration was 2.2 and 0.6 mm for FDK-CBCT and iCBCT, respectively. Conclusion: Use of iCBCT reconstruction algorithm can generally reduce the patient dose by approximately two-thirds compared to conventional reconstruction methods while maintaining low-contrast detectability and accuracy of registration. [ABSTRACT FROM AUTHOR]

This paper describes the ongoing structure of radiation oncology in Japan in terms of equipment, personnel, patient load and geographic distribution to identify and overcome any existing limitations. From December 2014 to July 2017, the Japanese Society for Radiation Oncology conducted a questionnaire based on the Japanese national structure survey of radiation oncology in 2013. Data were analyzed based on institutional stratification by the annual number of new patients treated with radiotherapy per institution. The estimated annual numbers of new and total (new plus repeat) patients treated with radiation were 216 000 and 257 000, respectively. Additionally, the estimated cancer incidence was 862 452 cases with ~25.0% of all newly diagnosed patients being treated with radiation. The types and numbers of treatment devices actually used included linear accelerator (LINAC; n  = 880), Gamma Knife (n  = 45), 60Co remote afterloading system (RALS; n  = 23) and 192Ir RALS (n  = 128). The LINAC system used dual-energy functions in 675 units, 3D conformal radiotherapy functions in 785 and intensity-modulated radiotherapy (IMRT) functions in 494. There were 831 Japan Radiological Society/Japanese Society for Radiation Oncology-certified radiation oncologists, 1130.6 full-time equivalent (FTE) radiation oncologists, 2214.6 FTE radiotherapy technologists, 196.6 FTE medical physicists, 183.8 FTE radiotherapy quality managers and 856.7 FTE nurses. The frequency of IMRT use significantly increased during this time. In conclusion, the Japanese structure of radiation oncology has clearly improved in terms of equipment and utility although there was a shortage of personnel in 2013. [ABSTRACT FROM AUTHOR]

Background: A phase II study of adaptive two-step intensity-modulated radiotherapy (IMRT) with chemotherapy for nasopharyngeal cancer (NPC) (JCOG1015) was conducted to evaluate the efficacy and safety. Methods: Patients aged 20–75 years with stages II–IVB NPC were enrolled. As adaptive two-step IMRT, computed tomography planning was performed twice before IMRT for the initial plan of 46 Gy/23 fractions and during treatment for the boost plan of 24 Gy/12 fractions with a total dose of 70 Gy. Chemotherapy (cisplatin 80 mg/m2/3-weeks × 3 courses) was administered concurrently with IMRT, followed by adjuvant chemotherapy (cisplatin at 70 mg/m2 with 5-FU 700 at mg/m2 for 5 days/4 weeks × 3 courses). Results: Between 2011 and 2014, 75 patients were enrolled from 12 institutions. The 3-year overall survival (OS) for the 75 patients was 88%, and the upper and lower limits of the 95% CI of 78%–94% were higher than the expected 3-year OS of 75% for the target population adjusted by the actual proportion of stage II:III:IV = 21%:44%:35%. The 3-year progression-free survival (PFS) and loco-regional PFS were 71% [59–80%] and 77% [66–85%], respectively. Although no grade 4–5 late toxicities were observed, 15 patients (20%) developed grade 3 late toxicities. Grade 2 xerostomia was noted in 26%, 12%, and 9% at 1, 2, and 3 years after starting IMRT, respectively. Conclusions: Adaptive two-step IMRT for NPC demonstrated an excellent 3-year OS with acceptable toxicities. This method may be one treatment option for locally advanced NPC. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate knowledge-based volume modulated arc therapy (VMAT) plans for oesophageal cancers using a model trained with plans optimised with a different treatment planning system (TPS) and to compare lung dose sparing in two TPSs, Eclipse and RayStation. Materials and methods: A total of 64 patients with stage I–III oesophageal cancers were treated using hybrid VMAT (H-VMAT) plans optimised using RayStation. Among them, 40 plans were used for training the model for knowledge-based planning (KBP) in RapidPlan. The remaining 24 plans were recalculated using RapidPlan to validate the KBP model. H-VMAT plans calculated using RapidPlan were compared with H-VMAT plans optimised using RayStation with respect to planning target volume doses, lung doses, and modulation complexity. Results: In the lung, there were significant differences between the volume ratios receiving doses in excess of 5, 10, and 20 Gy (V5, V10, and V20). The V5 for the lung with H-VMAT plans optimised using RapidPlan was significantly higher than that of H-VMAT plans optimised using RayStation (p <.01), with a mean difference of 10%. Compared to H-VMAT plans optimised using RayStation, the V10 and V20 for the lung were significantly lower with H-VMAT plans optimised using RapidPlan (p =.04 and p =.02), with differences exceeding 1.0%. In terms of modulation complexity, the change in beam output at each control point was more constant with H-VMAT plans optimised using RapidPlan than with H-VMAT plans optimised using RayStation. The range of the change with H-VMAT plans optimised using RapidPlan was one third that of H-VMAT plans optimised using RayStation. Conclusion: Two optimisers in Eclipse and RayStation had different dosimetric performance in lung sparing and modulation complexity. RapidPlan could not improve low lung doses, however, it provided an appreciate intermediated doses compared to plans optimised with RayStation. [ABSTRACT FROM AUTHOR]

We evaluated the evolving structure of radiation oncology in Japan in terms of equipment, personnel, patient load and geographic distribution to identify and overcome any existing limitations. From March 2012 to August 2015, the Japanese Society for Radiation Oncology conducted a questionnaire based on the Japanese national structure survey of radiation oncology in 2011. Data were analyzed based on the institutional stratification by the annual number of new patients treated with radiotherapy per institution. The estimated annual numbers of new and total (new plus repeat) patients treated with radiation were 211 000 and 250 000, respectively. Additionally, the estimated cancer incidence was 851 537 cases with approximately 24.8% of all newly diagnosed patients being treated with radiation. The types and numbers of treatment devices actually used included linear accelerator (LINAC; n  = 836), telecobalt (n  = 3), Gamma Knife (n  = 46), 60Co remote afterloading system (RALS; n  = 24), and 192Ir RALS (n  = 125). The LINAC system used dual-energy functions in 619 units, 3D conformal radiotherapy functions in 719 and intensity-modulated radiotherapy (IMRT) functions in 412. There were 756 JRS or JASTRO-certified radiation oncologists, 1018.5 full-time equivalent (FTE) radiation oncologists, 2026.7 FTE radiotherapy technologists, 149.1 FTE medical physicists, 141.5 FTE radiotherapy quality managers and 716.3 FTE nurses. The frequency of IMRT use significantly increased during this time. To conclude, although there was a shortage of personnel in 2011, the Japanese structure of radiation oncology has clearly improved in terms of equipment and utility. [ABSTRACT FROM AUTHOR]

The article presents a study about the respiratory gated and non-gated stereotactic body radiotherapy for lung cancer in an asymmetric margin setting at the cranial and caudal sides. It cites the objective of the study in evaluating its total error. The article also discusses the methods and results of the study by coordinating the tumor centres (TCs) in the craniocaudal direction.

OBJECTIVE To evaluate the clinical results of radiotherapy (RT) for patients with regionally localized hormone-refractory prostate carcinoma (HRPC). PATIENTS AND METHODS As part of a Patterns of Care Study in Japan, a nationwide survey was conducted of RT for patients with prostate adenocarcinoma. We reviewed the detailed information of 140 patients with regionally localized HRPC who received RT between 1996 and 1998, and between 1999 and 2001, in 117 randomly selected institutes in Japan. The median (range) age of the patients was 74 (51–94) years, and their tumours were defined as well (14), moderately (51) or poorly (54) differentiated, or of unknown differentiation (21). The median (range) interval between hormonal therapy (HT) and RT was 32.5 (1.1–168.4) months. Ninety-five patients had T3-4 tumours and 28 had regional lymph node metastases before treatment. The median (range) prostate-specific antigen levels before the initial HT and before RT were 35.0 (1.5–276) and 10.0 (0.06–760.3) ng/mL, respectively. External beam RT was administered, with a median total dose of 66 Gy; 70 patients (50%) received pelvic irradiation. RESULTS At a median follow-up of 20.7 months, the 5-year overall and clinical progression-free survival rates (95% confidence interval) were 48.1 (36–60)% and 36.7 (26–47)%, respectively. Although there were distant metastases in 46 patients, only six had local progression. There was late morbidity of grade ≥3 in six patients. CONCLUSION To the best of our knowledge, this study comprises the largest series of regionally localized HRPC treated with RT reported to date. RT might have a limited role for HRPC, because in most patients RT failed, with distant metastasis. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the structure of radiation oncology in Japan in terms of equipment, personnel, patient load, and geographic distribution to identify and improve any deficiencies. Methods and Materials: A questionnaire-based national structure survey was conducted between March 2006 and February 2007 by the Japanese Society of Therapeutic Radiology and Oncology. These data were analyzed in terms of the institutional stratification of the Patterns of Care Study. Results: The total numbers of new cancer patients and total cancer patients (new and repeat) treated with radiotherapy in 2005 were estimated at approximately 162,000 and 198,000, respectively. In actual use were 765 linear accelerators, 11 telecobalt machines, 48 GammaKnife machines, 64 60Co remote-controlled after-loading systems, and 119 192Ir remote-controlled after-loading systems. The linear accelerator systems used dual-energy function in 498 systems (65%), three-dimensional conformal radiotherapy in 462 (60%), and intensity-modulated radiotherapy in 170 (22%). There were 426 Japanese Society of Therapeutic Radiology and Oncology-certified radiation oncologists, 774 full-time equivalent radiation oncologists, 117 medical physicists, and 1,635 radiation therapists. Geographically, a significant variation was found in the use of radiotherapy, from 0.9 to 2.1 patients/1,000 population. The annual patient load/FTE radiation oncologist was 247, exceeding the Blue Book guidelines level. Patterns of Care Study stratification can clearly discriminate the maturity of structures according to their academic nature and caseload. Conclusions: The Japanese structure has clearly improved during the past 15 years in terms of equipment and its use, although the shortage of manpower and variations in maturity disclosed by this Patterns of Care Study stratification remain problematic. These constitute the targets for nationwide improvement in quality assurance and quality control. [Copyright &y& Elsevier]

Purpose: Human papillomavirus (HPV)-related squamous cell carcinoma of the oropharynx (OPSCC) is extremely radiosensitive. Radiation therapy plus high-dose cisplatin remains the standard of care but causes long-term toxicity. Treatment deintensification approaches that reduce toxicity while maintaining survival are desirable for HPV-related OPSCC.Methods and Materials: We conducted a single-arm, multicenter, phase 2 trial. Patients with newly diagnosed, biopsy-proven, American Joint Committee on Cancer (seventh edition) stage III or IV OPSCC positive for both p16 and HPV DNA were eligible. Patients with T4, N3, or T1N1 disease were excluded. Smoking history was not included in eligibility criteria. Patients received intensity modulated radiation therapy (IMRT) of 70 Gy in 35 fractions or 70.4 Gy in 32 fractions without chemotherapy. The primary endpoint was complete response or complete metabolic response 10 weeks after IMRT completion.Results: Between September 13, 2013, and November 15, 2016, 39 patients were enrolled according to a 2-stage Simon design. Twenty-three patients (59%) had smoked for more than10 pack-years. Thirty-six patients (92%) had tumors genotyped as HPV16. Thirty-seven patients (95%) received full-dose radiation therapy and 35 (90%) had complete response or complete metabolic response. Median follow-up was 51 months (interquartile range, 41-63 months). One patient (3%) had regional recurrence and 3 (8%) had distant metastasis. One patient died of disease. The 2-year progression-free survival rate was 94% (95% CI, 81%-99%), and the 2-year overall survival rate was 100%. Common grade 3 adverse events during IMRT included mucositis in 10 patients (26%) and dysphagia in 7 patients (18%). No patients were dependent on a feeding tube at 1 month after IMRT completion. No grade 3 or 4 late adverse events were observed.Conclusions: IMRT alone is associated with excellent response as well as reduced toxicity and could be a treatment option for carefully selected patients with locally advanced "true" HPV-related OPSCC. Further studies are warranted. [ABSTRACT FROM AUTHOR]

• This study proposes a functional image based SBRT planning for liver tumors. • The normalized iodine density map from DECT showed strong correlation with FIB-4. • The proposed method could reduce doses to the high functional liver volume. • The target coverage was comparable with the standard clinical plan. This study aimed to generate a functional image of the liver using dual-energy computed tomography (DECT) and a functional-image-based stereotactic body radiation therapy plan to minimize the dose to the volume of the functional liver (V fl). A normalized iodine density (NID) map was generated for fifteen patients with liver tumors. The volume of liver with an NID < 0.46 was defined as V fl , and the ratio between V fl and the total volume of the liver (FLR) was calculated. The relationship between the FLR and Fibrosis-4 (FIB-4) was assessed. For patients with 15% < FLR < 85%, functional volumetric modulated-arc therapy plans (F-VMAT) were retrospectively generated to preserve V fl , and compared to the clinical plans (C-VMAT). FLR showed a significantly strong correlation with FIB-4 (r = −0.71, p < 0.01). For ten generated F-VMAT plans, the dosimetric parameters of D 99% , D 50% , D 1% and the conformity index were comparable to those of the C-VMAT (p > 0.05). For V fl , F-VMAT plans achieved lower V 5Gy (122.4 ± 31.7 vs 181.1 ± 57.3 cc), V 10Gy (44.4 ± 22.2 vs 98.2 ± 33.3 cc), V 15Gy (22.6 ± 20.3 vs 49.8 ± 33.7 cc), V 20Gy (11.6 ± 14.1 vs 24.9 ± 25.1 cc), and D mean (3.9 ± 2.3 vs 5.8 ± 3.0 Gy) values than the C-VMAT plans (p < 0.01). The functional image derived from DECT was successfully used, allowing for a reduction in the dose to the V fl without compromising target coverage. [ABSTRACT FROM AUTHOR]

Highlights • The tube feeding dependence was lower than expected by the original NTCP model. • The closed testing procedure indicated that adjustment of the intercept was needed. • The oral tongue could be new organ at risk for tube feeding dependence. Abstract Background and purpose The purpose of this study was to externally validate a previously published normal tissue complication probability (NTCP) model for tube feeding dependence at 6 months (TUBE M6) after completion of (chemo) radiotherapy. Materials and methods This study evaluated 122 head and neck cancer patients treated by definitive (chemo) radiotherapy. The closed testing procedure was used to select the appropriate method for updating the NTCP model. In this procedure, the likelihood ratio test was used to compare the updated model against the original model. Results Mean predicted NTCP was 12.2% (95% CI: 9.9%–14.5%) when using the original NTCP model for TUBE M6. TUBE M6 at our institute was 5.7% (95% CI: 1.8–9.6%) for the 122 patients evaluated. The test for the model revision against the original NTCP model was statistically significant (p = 0.032). The test for the model revision against the model adjusting intercept only was not statistically significant (p = 0.240). According to the closed testing procedure, the model required adjusting the intercept only. Conclusions TUBE M6 at our institute was lower than that predicted by the original NTCP model. The closed testing procedure indicated that only an adjustment of the intercept was needed indicating the importance of external validation. [ABSTRACT FROM AUTHOR]

Purpose: The patterns of care study (PCS) of radiotherapy for cervical cancer in Japan over the last 10 years was reviewed. Methods and Materials: The Japanese PCS working group analyzed data from 1,200 patients (1995–1997, 591 patients; 1999–2001, 324 patients; 2003–2005, 285 patients) with cervical cancer treated with definitive radiotherapy in Japan. Results: Patients in the 2001–2003 survey were significantly younger than those in the 1999–2001 study (p < 0.0001). Histology, performance status, and International Federation of Gynecology and Obstetrics stage were not significantly different among the three survey periods. Use of combinations of chemotherapy has increased significantly during those periods (1995–1997, 24%; 1999–2001, 33%; 2003–2005, 54%; p < 0.0001). The ratio of patients receiving concurrent chemotherapy has also dramatically increased (1995–1997, 20%; 1999–2001, 54%; 2003–2005, 83%; p < 0.0001). As for external beam radiotherapy (EBRT), the application rate of four-field portals has greatly increased over the three survey periods (1995–1997, 2%; 1999–2001, 7%; 2003–2005, 21%; p < 0.0001). In addition, the use of an appropriate beam energy for EBRT has shown an increase (1995–1997, 67%; 1999–2001, 74%; 2003–2005, 81%; p = 0.064). As for intracavitary brachytherapy (ICBT), an iridium source has become increasingly popular (1995–1997, 27%; 1999–2001, 42%; 2003–2005, 84%; p < 0.0001). Among the three surveys, the ratio of patients receiving ICBT (1995–1997, 77%; 1999–2001, 82%; 2003–2005, 78%) has not changed. Although follow-up was inadequate in each survey, no significant survival differences were observed (p = 0.36), and rates of late Grade 3 or higher toxicity were significantly different (p = 0.016). Conclusions: The Japanese PCS has monitored consistent improvements over the past 10 years in the application of chemotherapy, timing of chemotherapy, and EBRT methods. However, there is still room for improvement, especially in the clinical practice of ICBT. [Copyright &y& Elsevier]

Abstract: Objective: Cancer staging systems should be responsive to the development of diagnostic tools. The International Federation of Gynecology and Obstetrics (FIGO) cervical cancer guidelines were modified in 2009 regarding the pretreatment assessment. We report the recent Japanese patterns of pretreatment workup for cervical cancer. Methods: The Japanese Patterns of Care Study (PCS) working group analyzed the pretreatment diagnostic assessment data of 609 patients with cervical cancer treated with definitive radiotherapy in the two survey periods (1999–2001, 324; 2003–2005, 285) in Japan. Sixty-one of 640 institutions were selected for this survey using a stratified two-staged cluster sampling method. Results: The use of optional examinations in the latest FIGO guidelines such as intravenous urography, cystoscopy, and proctoscopy was gradually decreasing. Surgical staging was rarely performed in either survey period. Computed tomography (CT) and magnetic resonance imaging (MRI) were widely used, and MRI has become increasingly prevalent even between the two survey periods. Primary lesion size and pelvic lymph node status was evaluated by CT/MRI for most patients in both surveys. Conclusions: The use of CT/MRI that is encouraged in the latest FIGO staging guidelines already replaced intravenous urography, cystoscopy, and proctoscopy in Japan. Japanese patients received the potential benefit of CT/MRI because prognostic factors such as primary lesion size and pelvic lymph node status were evaluated by these modalities. The use of cystoscopy and proctoscopy should be continuously monitored in the future PCS survey because only CT/MRI could lead to the stage migration for patients on suspicion of bladder/rectum involvement on CT/MRI. [Copyright &y& Elsevier]

Purpose: To delineate changing trends in radical external beam radiotherapy (EBRT) for prostate cancer in Japan. Methods and Materials: Data from 841 patients with clinically localized prostate cancer treated with EBRT in the Japanese Patterns of Care Study (PCS) from 1996 to 2005 were analyzed. Results: Significant increases in the proportions of patients with stage T1 to T2 disease and decrease in prostate-specific antigen values were observed. Also, there were significant increases in the percentages of patients treated with radiotherapy by their own choice. Median radiation doses were 65.0 Gy and 68.4 Gy from 1996 to 1998 and from 1999 to 2001, respectively, increasing to 70 Gy from 2003 to 2005. Moreover, conformal therapy was more frequently used from 2003 to 2005 (84.9%) than from 1996 to 1998 (49.1%) and from 1999 to 2001 (50.2%). On the other hand, the percentage of patients receiving hormone therapy from 2003 to 2005 (81.1%) was almost the same as that from 1996 to 1998 (86.3%) and from 1999 to 2001 (89.7%). Compared with the PCS in the United States, patient characteristics and patterns of treatments from 2003 to 2005 have become more similar to those in the United States than those from 1996 to 1998 and those from 1999 to 2001. Conclusions: This study indicates a trend toward increasing numbers of patients with early-stage disease and increasing proportions of patients treated with higher radiation doses with advanced equipment among Japanese prostate cancer patients treated with EBRT during 1996 to 2005 survey periods. Patterns of care for prostate cancer in Japan are becoming more similar to those in the United States. [Copyright &y& Elsevier]

Purpose: To develop an infrastructure for the integrated Monte Carlo verification system (MCVS) to verify the accuracy of conventional dose calculations, which often fail to accurately predict dose distributions, mainly due to inhomogeneities in the patient''s anatomy, for example, in lung and bone. Methods and Materials: The MCVS consists of the graphical user interface (GUI) based on a computational environment for radiotherapy research (CERR) with MATLAB language. The MCVS GUI acts as an interface between the MCVS and a commercial treatment planning system to import the treatment plan, create MC input files, and analyze MC output dose files. The MCVS consists of the EGSnrc MC codes, which include EGSnrc/BEAMnrc to simulate the treatment head and EGSnrc/DOSXYZnrc to calculate the dose distributions in the patient/phantom. In order to improve computation time without approximations, an in-house cluster system was constructed. Results: The phase-space data of a 6-MV photon beam from a Varian Clinac unit was developed and used to establish several benchmarks under homogeneous conditions. The MC results agreed with the ionization chamber measurements to within 1%. The MCVS GUI could import and display the radiotherapy treatment plan created by the MC method and various treatment planning systems, such as RTOG and DICOM-RT formats. Dose distributions could be analyzed by using dose profiles and dose volume histograms and compared on the same platform. With the cluster system, calculation time was improved in line with the increase in the number of central processing units (CPUs) at a computation efficiency of more than 98%. Conclusions: Development of the MCVS was successful for performing MC simulations and analyzing dose distributions. [Copyright &y& Elsevier]

Purpose: To describe patient characteristics and the process of radiotherapy (RT) for patients with esophageal cancer treated between 1999 and 2001 in Japan. Methods and Materials: The Japanese Patterns of Care Study (PCS) Working Group conducted a third nationwide survey of 76 institutions. Detailed information was accumulated on 621 patients with thoracic esophageal cancer who received RT. Results: The median age of patients was 68 years. Eighty-eight percent were male, and 12% were female. Ninety-nine percent had squamous cell carcinoma histology. Fifty-five percent had the main lesion in the middle thoracic esophagus. Fourteen percent had clinical Stage 0–I disease, 32% had Stage IIA–IIB, 43% had Stage III, and 10% had Stage IV disease. Chemotherapy was given to 63% of patients; 39% received definitive chemoradiotherapy (CRT) without surgery and 24% pre- or postoperative CRT. Sixty-two percent of the patients aged ≥75 years were treated with RT only. Median total dose of external RT was 60 Gy for definitive CRT patients, 60 Gy for RT alone, and 40 Gy for preoperative CRT. Conclusions: This PCS describes general aspects of RT for esophageal cancer in Japan. Squamous cell carcinoma accounted for the majority of patients. The standard total external RT dose for esophageal cancer was higher in Japan than in the United States. Chemoradiotherapy had become common for esophageal cancer treatment, but patients aged ≥75 years were more likely to be treated by RT only. [Copyright &y& Elsevier]

Purpose: To analyze retrospectively the results of external beam radiotherapy for clinically localized hormone-refractory prostate cancer and investigate the clinical significance of nadir prostate-specific antigen (PSA) value within 12 months (nPSA12) as an early estimate of clinical outcomes after radiotherapy. Methods and Materials: Eighty-four patients with localized hormone-refractory prostate cancer treated with external beam radiotherapy were retrospectively reviewed. The total radiation doses ranged from 30 to 76 Gy (median, 66 Gy), and the median follow-up period for all 84 patients was 26.9 months (range, 2.7–77.3 months). Results: The 3-year actuarial overall survival, progression-free survival (PFS), and local control rates in all 84 patients after radiotherapy were 67%, 61%, and 93%, respectively. Although distant metastases and/or regional lymph node metastases developed in 34 patients (40%) after radiotherapy, local progression was observed in only 5 patients (6%). Of all 84 patients, the median nPSA12 in patients with clinical failure and in patients without clinical failure was 3.1 ng/mL and 0.5 ng/mL, respectively. When dividing patients according to low (<0.5 ng/mL) and high (≥0.5 ng/mL) nPSA12 levels, the 3-year PFS rate in patients with low nPSA12 and in those with high nPSA12 was 96% and 44%, respectively (p < 0.0001). In univariate analysis, nPSA12 and pretreatment PSA value had a significant impact on PFS, and in multivariate analysis nPSA12 alone was an independent prognostic factor for PFS after radiotherapy. Conclusions: External beam radiotherapy had an excellent local control rate for clinically localized hormone-refractory prostate cancer, and nPSA12 was predictive of clinical outcomes after radiotherapy. [Copyright &y& Elsevier]

Purpose: To describe the patterns of definitive radiotherapy practice for patients with uterine cervical cancer from 1999 to 2001 in Japan. Methods and Materials: The Japanese Patterns of Care Study (JPCS) working group conducted a third extramural audit survey of 68 institutions and collected specific information on 324 cervical cancer patients treated with definitive radiotherapy. Results: Almost all patients (96%) were treated with whole pelvic radiotherapy using opposing anteroposterior fields (87%). A midline block was used in 70% of the patients. Intracavitary brachytherapy (ICBT) was applied in 82% of cases. Most patients (89%) were treated with high-dose rate (HDR) ICBT. Calculation of doses to organs at risk (ICRU 38) was performed for rectum in 25% of cases and for bladder in 18% of cases. Only 3% of patients were given intravenous conscious sedation during ICBT applicator insertions. The median total biologically effective dose at point A (EBRT+ICBT) was 74 Gy10 in cases treated with HDR-ICBT. There was no significant difference in total biologically effective dose between stages. The median overall treatment time was 47 days. Concurrent chemoradiation was applied in 17% of patients. Conclusions: This study describes the general patterns of radiotherapy practice for uterine cervical cancer in Japan. Although methods of external radiotherapy seemed to be appropriate, there was room for improvement in ICBT practice, such as pretreatment. A substantial difference in total radiotherapy dose between Japan and the United States was observed. [Copyright &y& Elsevier]

Purpose: The aim of this study was to evaluate the efficacy and toxicity of moderate dose radiation therapy (RT) for mucosa-associated lymphoid tissue (MALT) lymphoma in a prospective multicenter phase II trial. Methods and Materials: The subjects in this study were 37 patients with MALT lymphoma between April 2002 and November 2004. There were 16 male and 21 female patients, ranging in age from 24 to 82 years, with a median of 56 years. The primary tumor originated in the orbit in 24 patients, in the thyroid and salivary gland in 4 patients each, and 5 in the others. The median tumor dose was 30.6 Gy (range, 30.6–39.6 Gy), depending on the primary site and maximal tumor diameter. The median follow-up was 37.3 months. Results: Complete remission (CR) or CR/unconfirmed was achieved in 34 patients (92%). The 3-year overall survival, progression-free survival, and local control probability were 100%, 91.9%, and 97.3%, respectively. Thirteen patients experienced Grade 1 acute toxicities including dermatitis, mucositis, and conjunctivitis. One patient developed Grade 2 taste loss. Regarding late toxicities, Grade 2 reactions including hypothyroidism, and radiation pneumonitis were observed in three patients, and Grade 3 cataract was seen in three patients. Conclusions: This prospective phase II study demonstrated that moderate dose RT was highly effective in achieving local control with acceptable morbidity in 37 patients with MALT lymphoma. [Copyright &y& Elsevier]

Summary: To investigate the practice process of postoperative radiation therapy for non-small-cell lung cancer (NSCLC) in Japan. Between April 2002 and March 2004, the Patterns of Care Study conducted an extramural audit survey for 76 of 556 institutions using a stratified two-stage cluster sampling. Data on treatment process of 627 patients with NSCLC who received radiation therapy were collected. Ninety-nine (16%) patients received postoperative radiation therapy between 1999 and 2001 (median age, 65 years). Pathological stage was stage I in 8%, II in 17%, IIIA in 44%, and IIIB in 20%. The median field size was 9cm×11cm, and median total dose was 50Gy. Photon energies of 6MV or higher were used for 64 patients, whereas a cobalt-60 unit was used for five patients. Three-dimensional conformal treatment was used infrequently. Institutional stratification influenced several radiotherapy parameters such as photon energy and planning target volume. Smaller non-academic institutions provided worse quality of care. The study confirmed continuing variation in the practice of radiotherapy according to stratified institutions. Outdated equipment such as Cobalt-60 units was used, especially in non-academic institutions treating only a small number of patients per year. [Copyright &y& Elsevier]

: PurposeTo evaluate the quality of radiotherapy (RT) in Japan, we have been carrying out a national survey through patterns-of-care studies (PCSs) since 1996. We present the preliminary results of surgery combined with RT with or without chemotherapy for thoracic esophageal cancer.: Methods and materialsA Japanese PCS data format for esophageal cancer was established based on one used in the United States and including information used in the surgical registration system in Japan, so that the results in both countries could be compared. An independent panel of radiation oncologists surveyed randomly selected institutions and patients between September 1998 and March 2001. There were 767 esophageal cancer patients, of whom 220 had undergone preoperative or postoperative RT.: ResultsThe median age of the 220 patients was 62.3 years (range 31–89); of them, 88.1% were men. Pathologically, 218 patients (99.5%) had squamous cell carcinoma, predominantly located in the middle and lower thoracic esophagus, 41.7% of the patients had Stage III disease; they accounted for 52.6% of patients in nonacademic institutions and for 37.7% of those in academic institutions (p = 0.016). Sixty-nine patients received preoperative RT; of them, 60.9% received chemotherapy; 145 patients received postoperative RT with or without chemotherapy. The spinal cord of 23 (11.7%) of 196 patients was irradiated with ≥50 Gy. In academic institutions, extended radical “three-field” lymphatic dissection was performed for 72 (48.7%) of 148 patients; however, this sophisticated surgical procedure was done in only 13 (25.5%) of 51 patients in nonacademic settings (p = 0.004). In all large academic institutions (those treating ≥300 patients annually), ≥6 MV of photon energy was used; 30.5% of nonacademic institutes had linear accelerators of <6 MV photon (p = 0.001). No deviations occurred in the radiation dose (median 46 Gy), fractionations, or fields between the two types of institutions. Univariate analyses showed that the statistically significant prognostic factors affecting overall survival were stage (p = 0.001), extended radical “three-field” lymphatic dissection (p = 0.001), no residual tumor (p = 0.001), supraclavicular RT (p = 0.001), mediastinal RT (p = 0.025), Karnofsky performance status (p = 0.006) photon energy (p = 0.011), and stratification of the institutions (p = 0.001). Multivariate analysis showed that the type of institution (p = 0.045, risk ratio = 0.604), stage (p 0.029, risk ratio = 0.572), no residual tumor (p = 0.006, risk ratio = 0.487), photon energy (p = 0.043, risk ratio = 0.579), and use of chemotherapy (p = 0.012, risk ratio = 1.907) significantly affected overall survival.: ConclusionThis PCS showed that in Japan important issues are present regarding RT for esophageal cancer that should be solved immediately, namely, treatment strategy, photon energy, and dose applied to the spinal cord. The PCS provided important information on how much improvement in structure and process would be required nationwide for RT of esophageal cancer. [Copyright &y& Elsevier]

The Patterns of Care Study (PCS) conducted a nationwide audit survey in order to establish the national practice process of radiation therapy for small-cell lung cancer (SCLC) and examined the influence of institutional stratification on the process of care in Japan. The PCS randomly sampled institutions and patients using a two-stage cluster method and surveyed the process of radiation therapy for 174 stage I–III SCLC patients according to the category of institution, stratified as follows: A1, academic institutions treating ≥300 patients a year; A2, <300 patients; B1, non-academic institutions treating ≥120 patients a year; and B2, <120 patients. Karnofsky performance status distributions showed significant variance by stratification of institutions (P=0.013). Patients treated on an outpatient basis accounted for 32% in A1, 23% in A2, 8% in B1, but only 5% in B2 (P=0.007). A photon energy ≥10 MV was used for 87% of patients in A1, 69% in A2, 54% in B1 and 23% in B2 (P=0.001). Contralateral hilus was irradiated for 11% of patients in A1, 17% in A2, 29% in B1 and 3% in B2 (P=0.001). Field size reduction during the treatment course was done for 77% of patients in A1, 54% in A2, 60% in B1 and 42% in B2 (P=0.007). Ninety-two percent of patients received combined chemotherapy and radiation therapy, and the most frequently used drugs were etoposide (91%) and cisplatin (69%). The results of clinical studies on SCLC had favorably penetrated into the clinical practice. However, the stratification of institutions significantly affected the process of radiation therapy in Japan. [Copyright &y& Elsevier]

Purpose: To investigate whether a novel iterative cone-beam computed tomography (CBCT) reconstruction algorithm reduces metal artifacts in head and neck patient images.Method: An anthropomorphic phantom and 35 patients with dental metal prostheses or implants were analyzed. All CBCT images were acquired using a TrueBeam linear accelerator and reconstructed with a Feldkamp-Davis-Kress algorithm-based CBCT (FDK-CBCT) and an iterative CBCT algorithm. The mean Hounsfield unit (HU) and standard deviation values were measured on the tongue near the metal materials and the unaffected region as reference values. The artifact index (AI) was calculated. For objective image analysis, the HU value and AI were compared between FDK-CBCT and iterative CBCT images in phantom and clinical studies. Subjective image analyses of metal artifact scores and soft tissue visualizations were conducted using a five-point scale by two reviewers in the clinical study.Results: The HU value and AI showed significant artifact reduction for the iterative CBCT than for the FDK-CBCT images (phantom study: 389.8 vs.-10.3 for HU value, 322.9 vs. 96.2 for AI, FDK-CBCT vs. iterative CBCT, respectively; clinical study: 210.3 vs. 69.0 for HU value, 149.6 vs. 70.7 for AI). The subjective scores in the clinical patient study were improved in the iterative CBCT images (metal artifact score: 1.1 vs. 2.9, FDK-CBCT vs. iterative CBCT, respectively; soft tissue visualization: 1.8 vs. 3.6).Conclusions: The iterative CBCT reconstruction algorithm substantially reduced metal artifacts caused by dental metal prostheses and improved soft tissue visualization compared to FDK-CBCT in phantom and clinical studies. [ABSTRACT FROM AUTHOR]

Purpose: To determine the efficacy of a definitive radiotherapy protocol using high-dose-rate intracavitary brachytherapy (HDR-ICBT) with a low cumulative dose schedule in nonbulky early-stage cervical cancer patients, we conducted a prospective multi-institutional study. Methods and Materials: Eligible patients had squamous cell carcinoma of the intact uterine cervix, Federation of Gynecologic Oncology and Obstetrics (FIGO) stages Ib1, IIa, and IIb, tumor size <40 mm in diameter (assessed by T2-weighted magnetic resonance imaging), and no pelvic/para-aortic lymphadenopathy. The treatment protocol consisted of whole-pelvis external beam radiotherapy (EBRT) of 20 Gy/10 fractions, pelvic EBRT with midline block of 30 Gy/15 fractions, and HDR-ICBT of 24 Gy/4 fractions (at point A). The cumulative biologically effective dose (BED) was 62 Gy10 (α/β = 10) at point A. The primary endpoint was the 2-year pelvic disease progression-free (PDPF) rate. All patients received a radiotherapy quality assurance review. Results: Between September 2004 and July 2007, 60 eligible patients were enrolled. Thirty-six patients were assessed with FIGO stage Ib1; 12 patients with stage IIa; and 12 patients with stage IIb. Median tumor diameter was 28 mm (range, 6–39 mm). Median overall treatment time was 43 days. Median follow-up was 49 months (range, 7–72 months). Seven patients developed recurrences: 3 patients had pelvic recurrences (2 central, 1 nodal), and 4 patients had distant metastases. The 2-year PDPF was 96% (95% confidence interval [CI], 92%–100%). The 2-year disease-free and overall survival rates were 90% (95% CI, 82%–98%) and 95% (95% CI, 89%–100%), respectively. The 2-year late complication rates (according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer of Grade ≥1) were 18% (95% CI, 8%–28%) for large intestine/rectum, 4% (95% CI, 0%–8%) for small intestine, and 0% for bladder. No Grade ≥3 cases were observed for genitourinary/gastrointestinal late complications. Conclusions: These results suggest that definitive radiotherapy using HDR-ICBT with a low cumulative dose schedule (BED, 62 Gy10 at point A) can provide excellent local control without severe toxicity in nonbulky (<4-cm) early-stage cervical cancer. [ABSTRACT FROM AUTHOR]