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Background: Esophageal cancer is a lethal disease of global scope. Radiotherapy is the main method to treat esophageal cancer; however, it concurrently leads to malnutrition. Intensity-modulated radiotherapy (IMRT) is superior to three-dimensional conformal radiation therapy (3D-CRT) in dosimetry and clinical outcomes. In this cohort study, we aimed to compare the effect of 3D-CRT and IMRT on malnutrition status., Methods: We retrospectively included 79 esophageal cancer patients (IMRT: n=27, 3D-CRT: n=52) who received radiotherapy. We collected nutrition indexes at the beginning, the second week, and the end of radiotherapy. Paired-T test was used to evaluate the nutrition status during radiotherapy in each group. Chi-square test and independent-sample T -test were applied to compare the dynamic changes of indexes between IMRT and 3D-CRT groups., Results: The baselines of the two groups are comparable. Nutrition Risk Screening 2002 (NRS-2002) score, body weight, BMI, hemoglobin, lymphocyte, total protein, and albumin values were significantly reduced during radiotherapy in both groups. The dynamic changes of nutrition indexes during radiotherapy were not significantly different between the IMRT and 3D-CRT groups. Besides, no difference was found for radiation esophagitis or treatment completion between the two groups., Conclusions: Malnutrition occurs in esophageal cancer patients during radiotherapy. IMRT did not significantly decrease the risk of malnutrition compared to 3D-CRT., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2019 Journal of Thoracic Disease. All rights reserved.)

To investigate the effect of two modalities, radiotherapy (RT) and surgery plus entire hemithoracic radiotherapy (EHRT), on stage IVa thymoma. Patients enrolled in this study meet the following criteria: histologically proven thymoma; primary stage IVa or pleural dissemination after initial curative treatment. One treatment modality is intensity-modulated radiotherapy (IMRT) for pleural lesions with a dose ranging from 30-50 Gy, the other is macroscopically surgical resection plus EHRT with a dose of 13 Gy in 13 fractions. From July 2012 to April 2018, there were totally 56 patients enrolled in this study. The median age was 45 years old (range, 20-75 years old). There were 35 male and 21 female patients. The histology subtype distribution was 1 AB, 8 B1, 20 B2 and 27 B3, respectively. Thirty-one patients received IMRT for pleural dissemination and the response rate (CR + PR) was 97%. The mean local control time was 40 months (95% CI, 32.6-47.3 months). The in-field and out-field recurrence were 32% and 94%, respectively. The 2-year progression free survival (PFS) was 18%. While for patients who were treated by surgery plus EHRT, the in- and out-field recurrence were 8% and 16%, respectively. The 2-year PFS was 40%. The 2-year PFS for B1, B2 and B3 were 20%, 50% and 23%, respectively (P=0.255). Major toxicity occurred in IMRT group, 5 died of radiation-induced pneumonitis. Both IMRT and surgery plus EHRT showed good local control for stage IVa thymoma. Since stage IVa thymoma has a tendency to involve the whole hemithorax, surgery plus EHRT has a potential to produce longer PFS., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/med.2019.02.01). The series “Dedicated to the 9th International Thymic Malignancy Interest Group Annual Meeting (ITMIG 2018)” was commissioned by the editorial office without any funding or sponsorship. WF serves as an unpaid Editor-in-Chief of Mediastinum. The authors have no other conflicts of interest to declare., (2019 Mediastinum. All rights reserved.)

Background: To evaluate the potential dosimetric gains of helical tomotherapy (HT) versus intensity-modulated radiotherapy (IMRT) and volume-modulated arc therapy (VMAT) for craniospinal axis irradiation (CSI) of medulloblastoma., Methods: A total of 36 treatment plans were calculated retrospectively for 12 patients with medulloblastoma receiving CSI using HT with TomoTherapy Hi-Art Software (Version 2.0.7) (Accuray, Madison, WI, USA). For each case, the other two different delivery techniques were re-planned with IMRT/VMAT optimized with Eclipse treatment planning system (TPS) (Version 11.0.31). Homogeneity index (HI) and conformity index (CI) of the planning target volume (PTV) and organs at risk (OARs) sparing were analyzed. Differences in plans were evaluated using paired-samples t -test for various dosimetric parameters., Results: HT yielded the highest CI in all PTV coverage including PTV of gross tumor volume (PGTV) (HT: 0.7163; VMAT: 0.6688; IMRT: 0.6096), PTVbrain (HT: 0.8490; VMAT: 0.8384; IMRT: 0.7815) and PTVspine (HT: 0.5904; VMAT: 0.5862; IMRT: 0.5797). Meanwhile, HT yielded better HI in PGTV (HT: 0.0543; VMAT: 0.0759; IMRT: 0.0736), PTVbrain (HT: 0.5525; VMAT: 0.5619; IMRT: 0.5554) and PTVspine (HT: 0.0700; VMAT: 0.0782; IMRT: 0.0877). As for OARs, HT demonstrated marked superiority in critical organs including maximal/mean doses of brainstem PRV, optical chiasm and optic nerves., Conclusions: For CSI of medulloblastoma, HT offers superior outcomes in terms of PTV conformity, PTV homogeneity and critical OAR sparing as compared with IMRT/VMAT., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr.2019.01.30). The authors have no conflicts of interest to declare., (2019 Translational Cancer Research. All rights reserved.)

Introduction: The use of intensity-modulated radiation therapy (IMRT) in head and neck cancers has allowed for selective sparing of low-risk or uninvolved lymph nodes. In oropharyngeal cancers, the benefits and risks of omitting contralateral retropharyngeal lymph nodes (RPLN) remain uncertain. This study examines the outcomes of elective coverage of contralateral RPLN in oropharyngeal cancer treated with definitive IMRT., Methods: We analyzed 54 patients with newly diagnosed unilateral tonsil or base of tongue squamous cell carcinoma with at most unilateral neck involvement (cN0-N2b) and no RPLN involvement. These patients had no prior head and neck irradiation and were treated with definitive radiotherapy or chemoradiotherapy between 2012 and 2017. Cumulative incidences of local/regional/distant failure were estimated using competing risks methodology, and overall survival (OS) was estimated using the Kaplan-Meier method., Results: All patients received elective nodal coverage to the ipsilateral RPLN, and 38 (62%) patients did not receive elective treatment of the contralateral RPLN. There were no significant differences in baseline characteristics. There were no contralateral RPLN failures observed. When comparing patients who received contralateral RP treatment with those who did not, there were no significant differences in two-year local failure (23% vs. 9%, p = 0.09), regional failure (18% vs. 4%, p = 0.12), or distant failure (15% vs. 9%, p = 0.62). Two-year OS was 89%. Mean parotid dose was not significantly lower after sparing vs. treating the contralateral RPLN (median 25.6 vs. 32.7 Gy, p = 0.15)., Conclusions: The omission of contralateral RPLN irradiation in tonsil or tongue base carcinomas with unilateral neck involvement is safe without compromising disease control., Competing Interests: The authors have declared that no competing interests exist.

Background: The purpose of this study was to establish a risk stratification model for feeding tube use in patients who undergo intensity-modulated radiotherapy (IMRT) for head and neck cancers., Methods: One hundred thirty-nine patients treated with definitive IMRT (+/- concurrent chemotherapy) for head and neck mucosal cancers were included in this study. Patients were recommended a prophylactic feeding tube and followed up by a dietician for at least 8 weeks postradiotherapy (post-RT). Potential prognostic factors were analyzed for risk and duration of feeding tube use for at least 25% of dietary requirements., Results: Many variables had significant effects on risk and/or duration of feeding tube use in univariate analyses. Subsequent multivariable analysis showed that T classification ≥3 and level 2 lymphadenopathy were the best independent significant predictors of higher risk and duration of feeding tube use, respectively, in oral cavity, pharyngeal, and supraglottic primaries., Conclusion: In patients treated with definitive IMRT, T classification ≥3 and level 2 lymphadenopathy can potentially stratify patients into 4 risk groups for developing severe dysphagia requiring feeding tube use., (© 2018 Wiley Periodicals, Inc.)

Introduction: In this study, we catalogued physics contributions in the Red Journal over the past three decades and compared publication trends with global publication trends., Methods: We used the website of the Red Journal (International Journal of Radiation Oncology, Biology, and Physics) to access physics contributions published between 1988 and 2017. The contributions were catalogued following taxonomy guidelines endorsed by the American Association of Physicists in Medicine. From each issue, publications classified as "Physics Contributions" or as "Technical Innovations" or listed a physicist as one of the primary authors was indexed. Results are presented using descriptive statistics; chi-square [Formula: see text] 2 testing were utilized to examine trends in contributions over 10-year time intervals. For global trend comparison of Red Journal physics contributions, we utilized PubMed database to obtain publication counts on the topics of interest., Results: A total of 2,852 physics contributions were indexed (86 volumes and 436 issues). Overall, 76% of contributions were photon-beam therapy applications, 15% brachytherapy, 7% particle-beam therapy, and 3% electron-beam therapy. [Formula: see text] 2 analyses revealed significant changes in this distribution over time (p<0.001). Brachytherapy accounted for 23% of publications in the first decade, compared to 7% in the third decade. Particle beam therapy accounted for 4% of publications in the first decade and 12% in the third decade. Among treatment techniques, three-dimensional conformal radiation therapy (3D-CRT) accounted for 64% of contributions in the first decade, compared to 3% in the third decade. Intensity-modulated radiation therapy (IMRT)/volumetric modulated arc therapy (VMAT) accounted for 4% in the first decade, compared to 54% in the third decade. Significant increases in the proportions of studies focused on motion management, functional imaging for treatment planning, and radiation safety/quality assurance during the third decade were observed (p<0.001)., Conclusion: Trends of physics publications in the Red Journal and globally, in general, largely mirror technological advances in the field of radiation oncology. These changes reflect a technological transition in the field over three decades from beam's-eye-view designed static treatment ports to functional imaging and knowledge-based treatment planning with biological dose optimization and real-time tumor tracking., Competing Interests: The authors have declared that no competing interests exist.

Objectives: We performed dynamic tumor-tracking IMRT (DTT-IMRT) in locally advanced pancreatic cancer (LAPC) patients using a gimbaled linac of Vero4DRT. The purpose of this study is to report the first clinical results., Methods: From June 2013 to June 2015, eleven LAPC patients enrolled in this study and DTT-IMRT was successfully performed. The locoregional progression free survival (LRPFS), distant metastasis free survival (DMFS), overall survival (OS), hematologic and gastrointestinal (GI) toxicities were evaluated. Oncologic outcomes were estimated using Kaplan-Meier analysis, and toxicities using CTCAE v4.0., Results: The median radiation dose was 48 Gy (range, 45-51) in 15 fractions. Concurrent chemoradiotherapy (CCRT) was performed using gemcitabine in 9 patients and S-1 in one, while one patient refused. With a median follow-up of 22.9 months, 1-year LRPFS, DMFS, and OS rates were 90.9%, 70.7%, and 100%, respectively. Median survival time was 23.6 months. Grade-3 leucopenia and neutropenia were observed in two (18%) and one patient (9%), respectively. Grade-2 acute GI toxicity occurred in 2 patients (18%) and late grade-3 in 1 patient (9%)., Conclusions: Preliminarily application of DTT-IMRT using a gimbaled linac on CCRT in LAPC patients resulted in excellent locoregional control and OS without severe toxicity., Competing Interests: CONFLICTS OF INTEREST T. Mizowaki accepted a donation for research from Mitsubishi Heavy Industries.

Background: The aim of this study was to determine the feasibility of omitting the clinical target volume (CTV) in patients with locally advanced non-small cell lung cancer (NSCLC) treated with intensity-modulated radiotherapy (IMRT) by comparing dosimetric characteristics of three different IMRT plans with or without CTV implementation., Methods: Thirteen patients with stage III NSCLC were reviewed. Target volumes were contoured such that the planning target volume (PTV) derived from the gross tumor volume (GTV) directly was named PTV&#95;g and that from GTV plus CTV margin was named PTV&#95;c. The PTV margin to generate PTV&#95;g or PTV&#95;c was the same within each case. Three IMRT plans were retrospectively generated to deliver: (I) 60 Gy to PTV&#95;g in plan&#95;routine; (II) 60 Gy to PTV&#95;c in plan&#95;CTV, and (III) 50 Gy to PTV&#95;c while the dose was simultaneously escalated to 60 Gy to PTV&#95;g in plan&#95;SIB, achieved using the simultaneous integrated boost (SIB) technique. Optimization was performed to minimize the dose volumes of the irradiated normal lung, heart, esophagus, and spinal cord. Dose distributions and dosimetric indexes for the target volumes and critical structures in the three plans were computed and compared., Results: In plan&#95;routine, the 50-Gy isodose line covered at least 95% of the GTV plus CTV margins in all 13 patients. The statistics showed better sparing of the organs at risk (OAR) in plan&#95;routine than in plan&#95;CTV, and the best OAR sparing in plan&#95;SIB., Conclusions: In patients with locally advanced lung cancer, IMRT planning without CTV implementation provides sufficient dose coverage of subclinical disease while reducing the dose to normal tissues. The omission of CTV was feasible in our cohort of patients. However, when CTV was implemented, IMRT planning that included the SIB technique had further dosimetric benefits to the patients. This strategy thus merits further evaluation in clinical trials., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: The purpose of this study is to investigate the feasibility of a simultaneously integrated boost to the hypoxic subvolume of nasopharyngeal carcinomas (NCPs) under the guidance of 18 F-fluoromisonidazole (FMISO) positron emission tomography (PET)/CT using volumetric-modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) techniques., Methods: Eight patients with NPC were treated with simultaneous integrated boost-IMRT (treatment plan named IMRT70) with dose prescriptions of 70 Gy, 66 Gy, 60 Gy, and 54 Gy to the gross tumor volume (GTV), positive neck nodes, the planning target volume (PTV), and the clinically negative neck, respectively. Based on the same datasets, experimental plans with the same dose prescription plus a dose boost of 14 Gy (an escalation of 20% of the prescription dose) to the hypoxic volume target contoured on the pretreatment 18 F-FMISO PET/CT imaging were generated using IMRT and VMAT techniques, respectively (represented by IMRT84 and VMAT84). Two or more arcs (approximately 2-2.5 arcs, totally rotating angle <1000 degrees) were used in VMAT plans and 9 equally separated fields in IMRT plans. Dosimetric parameters, total monitor units, and delivery time were calculated for comparative study of plan quality and delivery efficiency between IMRT84 and VMAT84., Results: In experimental plans, hypoxic target volumes successfully received the prescribed dose of 84 Gy in compliance with other dose constraints with either the IMRT technique or the VMAT technique. In terms of the target coverage, dose homogeneity, and organs at risk (OAR) sparing, there was no statistically significant difference between the actual treatment plan of IMRT70 and experimental plans. The total monitor unit of VMAT84 (525.7 ± 39.8) was significantly less than IMRT70 (1171.5 ± 167; P = .001) and IMRT84 (1388.3 ± 151.0; P = .001) per fraction, with 55.1% and 62.1% reduction. The average machine delivery time was 3.5 minutes for VMAT plans in comparison with approximately 8 minutes for IMRT plans, resulting in a reduction factor of 56.2%. For experimental plans, the 3D gamma index average was over 98.0% with no statistical significant difference when a 3%/3 mm gamma passing rate criteria was used., Conclusion: With the guidance of 18 F-FMISO PET/CT imaging, dose escalation to hypoxic zones within NPC could be achieved and delivered efficiently with the VMAT technique in comparison with the IMRT technique., (© 2017 Wiley Periodicals, Inc.)

Background: The diagnosis and treatment of head and neck carcinoma of unknown primary (CUP) have changed with the introduction of fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT and intensity-modulated radiotherapy (IMRT), with potential implications for outcome., Methods: We conducted a retrospective analysis of 80 patients with head and neck CUP who were PET-staged and treated with curative intention using IMRT between 2006 and 2016 in the Netherlands Cancer Institute. Patient, tumor, and treatment demographics were recorded and oncologic outcomes were analyzed., Results: Local control was 100% in mucosal irradiated patients. Regional control was 90%. Ten patients developed distant metastases, which were associated with N3, extracapsular extension (ECE) and lower neck positive lymph nodes. Overall survival (OS) at 5 years was 62% and disease-specific survival was 78%. ECE, N3 neck, multiple levels of positive lymph nodes, and positive lymph nodes in the lower neck were associated with worse prognosis., Conclusion: Locoregional outcome of head and neck CUP managed with modern techniques is good. Future research needs to focus on reducing toxicity and patients prone for distant metastasis., (© 2017 Wiley Periodicals, Inc.)

In dynamic multi-leaf collimator (MLC) intensity-modulated radiotherapy (IMRT), the accuracy of delivered dose is influenced by the positional accuracy of the moving MLC. In order to assess the accuracy of the delivered dose during dynamic MLC IMRT, the delivered dose error in dynamic MLC IMRT using the MLC speed control with dose rate change was investigated. Sweeping gap sequence irradiation was performed with constant MLC leaf speed at 0.6 to 5 cm/s or changed MLC speed (4 steps). The positional accuracy of the moving MLC was evaluated from the trajectory log file. Absorbed dose measurements with sweeping field (Field size: 10 cm×10 cm, MLC leaf speed: 0.6 to 2.7 cm/s, MLC leaf gap width: 0.2 to 2.0 cm) were performed. The delivered dose error at each gap width was evaluated according to MLC leaf speed change. MLC positional errors and changes in delivered dose according to MLC leaf speed were within 0.07 mm and 0.6%, respectively, for all measurements. Beam hold-off did not occur under any conditions. We confirmed that TrueBeam can regulate MLC leaf speed below the maximum limit (2.5 cm/s) by changing the dose rate in real-time during irradiation in dynamic MLC IMRT. MLC gap error during irradiation was estimated within 0.2 mm at the maximum dose rate from the results of absolute dose measurements using dynamic MLC irradiation. In conclusion, TrueBeam can use the maximum dose rate for the treatment planning of dynamic MLC IMRT, which has an advantage of shorter treatment time.

We conducted a retrospective analysis to assess the toxicity and long-term survival of esophageal squamous cell carcinoma patients treated with three-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) versus conventional two-dimensional radiotherapy (2DRT). All data in the present study were based on four prospective clinical trials conducted at our institution from 1996 to 2004 and included 308 esophageal squamous cell carcinoma patients treated with 2DRT or 3DCRT/IMRT. Based on the inclusion and exclusion criteria, 254 patients were included in the analysis. Of these patients, 158 were treated with 2DRT, whereas 96 were treated with 3DCRT/IMRT. The rates of ≥Grade3 acute toxicity of the esophagus and lung were 11.5% versus 28.5% (P = 0.002) and 5.2% versus 10.8% (P = 0.127) in the 3DCRT/IMRT and 2DRT groups, respectively. The incidences of ≥Grade 3 late toxicity of the esophagus and lungs were 3.1% versus 10.7% (P = 0.028) and 3.1% versus 5.7% (P = 0.127) in the 3DCRT/IMRT and 2DRT groups, respectively. The 1-year, 3-year and 5-year estimated overall survival rates were 81%, 38% and 34% in the 3DCRT/IMRT group and 79%, 44% and 31% in the 2DRT group, respectively (P = 0.628). The 1-year, 3-year and 5-year local control rates were 88%, 71% and 66% in the 3DCRT/IMRT group and 84%, 66% and 60% in the 2DRT group, respectively (P = 0.412). Fewer incidences of acute and late toxicities were observed in esophageal squamous cell carcinoma patients treated with 3DCRT/IMRT compared with those treated with 2DRT. No significant survival benefit was observed with the use of 3DCRT/IMRT., (© 2015 International Society for Diseases of the Esophagus.)

Background: This retrospective study evaluates efficacy and tolerability of high-dose hypofractionated radiotherapy (RT) in patients with head and neck cancer., Methods: All patients with head and neck cancer treated between September 2003 and September 2013 with 12 × 4 Gy RT were included. Two and 3D-RT or intensity-modulated radiotherapy (IMRT) were used. Overall survival (OS), tumor response, and palliative effect were evaluated., Results: Palliative effect occurred in 63% of 81 included patients, lasted a median of 4.6 months, and was correlated with tumor response (p = .006). Median OS was 7.2 months. Confluent mucositis occurred more often in patients treated with 2D/3D-RT than IMRT (26% vs 44%; p = .04) and lasted for a median of 2 weeks., Conclusion: High-dose hypofractionated RT resulted in meaningful palliation in 63%, lasting for almost 5 months. IMRT should be the technique of choice, as it results in less high-grade toxicity. The 12 × 4 schedule should be opted for patients with reasonable functional capacities and a life expectancy of >6 months. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1264-E1270, 2016., (© 2015 Wiley Periodicals, Inc.)

Background: It is currently unclear whether the superior normal organ-sparing effect of intensity-modulated radiotherapy (IMRT) compared with 3-dimensional radiotherapy (3D) has a clinical impact on survival and cardiopulmonary mortality in patients with esophageal cancer (EC)., Methods: The authors identified 2553 patients aged > 65 years from the Surveillance, Epidemiology, and End Results (SEER)-Medicare and Texas Cancer Registry-Medicare databases who had nonmetastatic EC diagnosed between 2002 and 2009 and were treated with either 3D (2240 patients) or IMRT (313 patients) within 6 months of diagnosis. The outcomes of the 2 cohorts were compared using inverse probability of treatment weighting adjustment., Results: Except for marital status, year of diagnosis, and SEER region, both radiation cohorts were well balanced with regard to various patient, tumor, and treatment characteristics, including the use of IMRT versus 3D in urban/metropolitan or rural areas. IMRT use increased from 2.6% in 2002 to 30% in 2009, whereas the use of 3D decreased from 97.4% in 2002 to 70% in 2009. On propensity score inverse probability of treatment weighting-adjusted multivariate analysis, IMRT was not found to be associated with EC-specific mortality (hazard ratio [HR], 0.93; 95% confidence interval [95% CI], 0.80-1.10) or pulmonary mortality (HR, 1.11; 95% CI, 0.37-3.36), but was significantly associated with lower all-cause mortality (HR, 0.83; 95% CI, 0.72-0.95), cardiac mortality (HR, 0.18; 95% CI, 0.06-0.54), and other-cause mortality (HR, 0.54; 95% CI, 0.35-0.84). Similar associations were noted after adjusting for the type of chemotherapy, physician experience, and sensitivity analysis removing hybrid radiation claims., Conclusions: In this population-based analysis, the use of IMRT was found to be significantly associated with lower all-cause mortality, cardiac mortality, and other-cause mortality in patients with EC., (© 2015 American Cancer Society.)

Background: We investigated the feasibility of reirradiation with intensity-modulated radiotherapy (IMRT) for recurrent T1 to T2 nasopharyngeal carcinoma (NPC) by assessing long-term survival and late complication rates., Methods: Sixty patients who had been previously irradiated were diagnosed with locally recurrent T1 to T2 NPC and underwent reirradiation with IMRT. Severe radiation toxicities were assessed., Results: The median follow-up time was 40.0 months. The 5-year local failure-free survival (LFFS), distant failure-free survival (DFFS), and overall survival (OS) rates were 85.7%, 96.1%, and 67.2%, respectively. Independent prognostic factors included primary gross tumor volume >20 cm and the presence of significant complications. The most common severe complications were headache (31.6%), mucosal necrosis (30.0%), cranial neuropathy (25.0%), and temporal lobe necrosis (21.6%). Thirty-nine patients (65.0%) developed at least one severe complication and 18 patients died as a result., Conclusion: Excellent disease control can be achieved by reirradiation with IMRT for recurrent T1 to T2 NPC. However, the main challenge remains severe late complications., (© 2015 Wiley Periodicals, Inc.)

Background and Purpose: This study compares dosimetric parameters of planning target volume (PTV) coverage and organs at risk (OAR) sparing when postoperative radiotherapy for gynecologic cancers is delivered using volumetric modulated arc therapy (VMAT) versus a four-field (4FLD) box technique., Material and Methods: From July to December 2012, women requiring postoperative radiation for gynecologic cancers were treated with a standardized VMAT protocol. Two sets of optimized 4FLD plans were retrospectively generated: one based on standard anatomical borders (4FLD) and one based on the clinical target volume (CTV) created for VMAT with a 2 cm expansion guiding field border placement (4FLD+2). Ninety-five percent isodose curves were generated to evaluate PTV coverage., Results: VMAT significantly improved dose conformity compared with 4FLD and 4FLD+2 plans (p < 0.001) and provided additional coverage of the PTV posteriorly and superiorly, corresponding to coverage of the presacral and proximal iliac vessels. There was a significant reduction in dose to all OARs with VMAT, including a 58% reduction in the volume of the small bowel receiving more than 45 Gy (p=0.005)., Conclusions: Despite treating a larger volume, radiotherapy using a 4FLD technique is less homogenous and provides inferior coverage of the PTV compared with VMAT. With meticulous treatment planning and delivery, VMAT effectively encompasses the PTV and minimizes dose to OARs.

Background: To evaluate the survival benefit of intensity-modulated radiotherapy (IMRT) compared with conventional two-dimensional radiotherapy (2D-CRT) in nasopharyngeal carcinoma (NPC) using a large cohort with long follow-up., Methods: We retrospectively analysed 7081 non-metastatic NPC patients who received curative IMRT or 2D-CRT from February 2002 to December 2011., Results: Of the 7081 patients, 2245 (31.7%) were administered IMRT, while 4836 (68.3%) were administered 2D-CRT. At 5 years, the patients administered IMRT had significantly higher local relapse-free survival (LRFS), loco-regional relapse-free survival (LRRFS), progression-free survival (PFS) and overall survival (OS) (95.6%, 92.5%, 82.1% and 87.4%, respectively) than those administered 2D-CRT (90.8%, 88.5%, 76.7% and 84.5%, respectively; p<0.001). The distant metastasis-free survival (DMFS) was higher for IMRT than 2D-CRT, with borderline significance (87.6% and 85.7%, respectively; p=0.056). However, no difference was observed between IMRT and 2D-CRT in nodal relapse-free survival (NRFS; 96.3% and 97.4%, respectively; p=0.217). Multivariate analyses showed that IMRT was an independent protective prognostic factor for LRFS, LRRFS and PFS, but not NRFS, DMFS or OS., Conclusions: IMRT provided an improved LRFS, LRRFS and PFS in both the early and advanced T classifications and overall stage for non-disseminated NPC compared with 2D-CRT. However, no significant advantage was observed in NRFS, DMFS or OS when IMRT was used., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

We investigated the clinical outcomes of helical tomotherapy in 23 patients aged ≥80 years with localized and locally advanced prostate cancer and compared the results with data from 171 patients under 80 years. All patients received helical tomotherapy in our hospital between September 2009 and October 2012. The median follow-up periods were 35 months in the aged group and 34 months in the younger group. The median prescribed dose in helical tomotherapy was 78 Gy in 39 fractions (range, 72-78 Gy). The 3-year overall survival and biochemical relapse-free rates were 92% and 96% in the aged group and 99.4% and 97.3% in the younger group, respectively. There was no significant difference between the two groups in the biochemical relapse-free rates. The 3-year cumulative incidences of late Grade 2 or higher rectal toxicity and urinary toxicity were 13% and 4.8% in the aged group and 7.0% and 1.2% in the younger group, respectively. There was no significant difference between the aged group and the younger group in the cumulative incidence rates of rectal toxicity or urinary toxicity. No patients exhibited Grade 4 or higher toxicity, and all patients improved with conservative therapy. Helical tomotherapy in super-elderly patients with localized and locally advanced prostate cancer had good biochemical control rates without severe late toxicity. Definitive helical tomotherapy may be the treatment of choice for patients with localized and locally advanced prostate cancer, even in those older than 80 years of age., (© The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: Previous publications have demonstrated conflicting results regarding body mass index (BMI) and prostate cancer (CaP) outcomes after definitive radiotherapy (RT) before the dose escalation era. The goal of the current study was to determine whether increasing BMI was associated with outcomes in men with localized CaP who were treated with dose-escalated RT., Methods: The authors identified patients with localized (T1b-T4N0M0) CaP who were treated with definitive intensity-modulated RT and image-guided RT from 2001 through 2010. BMI was analyzed as a continuous variable. Adjusting for confounders, multivariable competing risk and Cox proportional hazards regression models were used to assess the association between BMI and the risk of biochemical failure (BF), distant metastases (DM), cause-specific mortality (CSM), and overall mortality., Results: Of the 1442 patients identified, approximately 20% had a BMI <25 kg/m(2) , 48% had a BMI of 25 to 29.9 kg/m(2) , 23% had a BMI of 30 to 34.9 kg/m(2) , 6% had a BMI of 35 to 39.9 kg/m(2) , and 4% had a BMI of ≥40 kg/m(2) . The median follow-up was 47.6 months (range, 1-145 months), with a median age of 68 years (range, 36-89 years). The median dose was 78 grays (range, 76-80 grays) and 30% of patients received androgen deprivation therapy. Increasing BMI was found to be inversely associated with age (P<.001) and pretreatment prostate-specific antigen level (P = .018). On multivariable analysis, increasing BMI was associated with an increased risk of BF (hazard ratio [HR], 1.03; 95% confidence interval [95% CI], 1.00-1.07 [P = .042]), DM (HR, 1.07; 95% CI, 1.02-1.11 [P = .004]), CSM (HR, 1.15; 95% CI, 1.07-1.23 [P<.001]), and overall mortality (HR, 1.05; 95% CI, 1.02-1.08 [P = .004])., Conclusions: For patients with CaP receiving dose-escalated intensity-modulated RT with daily image-guidance, increasing BMI appears to be associated with an increased risk of BF, DM, CSM, and overall mortality., (© 2015 American Cancer Society.)

Background: Although endoscopic nasopharyngectomy and intensity-modulated radiotherapy (IMRT) have been reported to be useful in treating isolated local recurrent nasopharyngeal carcinoma (NPC), their efficacy needs to be revaluated with comparison to 2D conventional radiotherapy (RT)., Methods: Four hundred ten patients with recurrent NPC were retrospectively analyzed, among whom the patients underwent IMRT, endoscopic nasopharyngectomy, and 2D conventional RT., Results: The 5-year overall survival (OS) and distant metastasis-free survival were significantly higher in endoscopic nasopharyngectomy and IMRT groups than in 2D conventional RT group both in the entire series and in the subgroup of patients with recurrent T1 to 2 NPC (p < .05), except in the subgroup of recurrent T3 to 4 stratifications (IMRT vs 2D conventional RT; 28.8% vs 16.8%; p = .351). Furthermore, endoscopic nasopharyngectomy was associated with better OS than IMRT in the recurrent T1 to 2 subgroup (79.2% vs 62.1%; p = .007). Multivariate analysis indicated therapeutic modality was an independent predictor of OS and distant metastasis-free survival (p < .001)., Conclusion: Endoscopic nasopharyngectomy and IMRT are associated with an improved OS and distant metastasis-free survival of patients with recurrent NPC compared to 2D conventional RT in early recurrent disease., (© 2014 Wiley Periodicals, Inc.)

Background: The current study was conducted to assess acute and late adverse events (AEs), overall survival (OS), pelvic failure, regional failure, distant failure, and disease-free survival in a prospective phase 2 clinical trial of bevacizumab and pelvic intensity-modulated radiotherapy (IMRT) with chemotherapy in patients with high-risk endometrial cancer., Methods: Patients underwent a hysterectomy and lymph node removal, and had ≥1 of the following high-risk factors: grade 3 carcinoma with >50% myometrial invasion, grade 2 or 3 disease with any cervical stromal invasion, or known extrauterine extension confined to the pelvis. Treatment included pelvic IMRT and concurrent cisplatin on days 1 and 29 of radiation and bevacizumab (at a dose of 5 mg/kg on days 1, 15, and 29 of radiation) followed by adjuvant carboplatin and paclitaxel for 4 cycles. The primary endpoint was grade ≥3 AEs occurring within the first 90 days (toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0])., Results: A total of 34 patients were accrued from November 2009 through December 2011, 30 of whom were eligible and received study treatment. Seven of 30 patients (23.3%; 1-sided 95% confidence interval, 10.6%-36.0%) developed grade ≥3 treatment-related nonhematologic toxicities within 90 days; an additional 6 patients experienced grade ≥3 toxicities between 90 and 365 days after treatment. The 2-year OS rate was 96.7% and the disease-free survival rate was 79.1%. No patient developed a within-field pelvic failure and no patients with International Federation of Gynecology and Obstetrics stage I to IIIA disease developed disease recurrence after a median follow-up of 26 months., Conclusions: Postoperative bevacizumab added to chemotherapy and pelvic IMRT appears to be well tolerated and results in high OS rates at 2 years for patients with high-risk endometrial carcinoma., (© 2015 American Cancer Society.)

Curative treatment for base-of-tongue squamous cell carcinoma (BOT SCC) has evolved over time; however, comparative outcomes analysis for various treatment strategies is lacking. The authors reviewed the evolution of treatment modality and radiotherapy (RT) technique for 231 consecutive BOT SCC patients at our institution between 1981 and 2011. Treatment modalities included definitive chemoradiotherapy (chemoRT) (42%), definitive RT (33%), surgery followed by RT (20%), and surgery alone (5%). RT techniques included external beam plus interstitial brachytherapy (EBRT + IB) (37%), conventional EBRT (29%), intensity-modulated radiation therapy ± simultaneous integrated boost (IMRT ± SIB) (34%). Clinical characteristics and outcomes were stratified by modality or RT technique. Treatment modality evolved from definitive RT (1980s-1990s) to definitive chemoRT (1990s-2000s). RT technique evolved from EBRT + IB (1980s-1990s) to conventional EBRT (1990s-2000s) to IMRT + SIB (2000s). With median alive follow-up of 6 years (0.3-28 years), the 5-year LC, LRC, and OS rates were 80%, 73%, and 51%. There was no difference in distribution of gender, age, stage among treatment modalities. Definitive chemoRT had improved LRC (HR 1.6) and OS (HR 1.7) compared to definitive RT. IMRT + SIB had improved LRC (HR 3.2), DFS (HR 3.4), and OS (HR 3.0) compared to conventional EBRT. Over the past 30 years, BOT SCC treatment has undergone major paradigm shifts that incorporate nonsurgical functional preservation, concurrent chemotherapy, and advanced RT techniques. Excellent locoregional control and survival outcomes are associated with accelerated IMRT with chemotherapy., (© 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: The purpose of this study was to discuss if the adoption of intensity-modulated radiotherapy (IMRT) for hypopharyngeal squamous cell carcinoma (SCC) has improved the outcome., Methods: We compared 3-dimensional (3D) radiotherapy (RT) and IMRT in all patients with hypopharyngeal SCC treated with curative intent RT or chemoradiation therapy (CRT) from January 1, 2000, to February 28, 2010. Locoregional control, overall survival (OS), distant relapse rate, larynx preservation rate, and enteral feeding tube duration were analyzed., Results: Of 181 consecutive patients, 90 received 3D-RT and 91 received IMRT. At 3 years, the IMRT group had higher locoregional control compared with the 3D-RT group (75% vs 58%; p = .003), but similar OS (50% vs 52%; p = .99), distant relapse rate (23% vs 20%; p = .79), and larynx-preservation rate (90% vs 86%; p = .16). The 2-year enteral feeding tube dependency rate was similar in both groups (19% vs 18%; p = .12)., Conclusion: Patients with hypopharyngeal SCC treated with IMRT showed a higher locoregional control compared with 3D-RT. However, distant-relapse rate and OS remain comparable between treatment techniques., (© 2014 Wiley Periodicals, Inc.)

Background: The aim of the prospective phase II study was to evaluate the efficacy and toxicities of concurrent carboplatin with intensity-modulated radiotherapy (IMRT) in the treatment of nasopharyngeal carcinoma (NPC)., Patients and Methods: Between October 2005 and November 2011, 73 stage II-IVB NPC patients received IMRT 70 Gy concurrently with three cycles of carboplatin (AUC 5) every three weeks, followed by three cycles of adjuvant carboplatin (AUC 5) and 5-FU (1,000 mg/m(2)/day for four days) every four weeks. All patients were evaluated for tumour response using response evaluation criteria in solid tumour (RECIST) criteria, survival analysis using Kaplan-Meier methods, and toxicities according to common terminology criteria for adverse events (CTCAE) version 4.0., Results: At three months after chemoradiation, 82.2% and 17.8% of patients achieved complete and partial response, respectively. With a median follow-up of 48.1 months (1.3-97.8 months), 9.6% and 17.8% had local recurrence and distant metastasis, respectively. The median survival was not reached. A three-year overall survival was 83.6% and a progression-free survival was 65.3%. Regarding treatment compliance, 97.2%, 68.5% and 69.8% completed radiation treatment, concurrent carboplatin and adjuvant chemotherapy, respectively. Grade 3-4 acute toxicities were oral mucositis (16.4%), dysphagia (16.4%), xerostomia (15.1%) and haematotoxicity (6.8%)., Conclusions: Carboplatin concurrently with IMRT provided excellent tumour response, manageable toxicities and good compliance. This should be considered as an alternative treatment for NPC patients.

Purpose: To compare the efficacy of intensity-modulated radiotherapy, three-dimensional conformal radiotherapy, and conventional radiotherapy for cervical cancer treatment., Materials and Methods: Whole pelvis intensity-modulated radiotherapy, three-dimensional conformal radiotherapy, and conventional radiotherapy plans were designed for 16 patients with stage IIB cervical cancer, each using the prescribed dose of 50.4 Gy/28 fractions. Dose-volume histograms of the target volume and organs at risk were evaluated., Results: Compared to the 3D conformal and conventional radiotherapy plans, the intensity-modulated radiotherapy plan demonstrated superior conformal treatment. The mean planning target volume dose of all three plans reached the target effective therapeutic dose. The planning target volume dose of the intensity-modulated radiotherapy plan was significantly higher than that of either the three-dimensional conformal radiotherapy or conventional radiotherapy plan (P<0.05). When more than 30 Gy was administered in intensity-modulated radiotherapy, organs at risk including the small intestine, rectum, bladder, and bone marrow received a significantly reduced volume of radiation. In comparison of the average planning target volume doses, significant volume reductions in irradiation of organs at risk were obtained with full bladders., Conclusions: An intensity-modulated radiotherapy plan with appropriate margins encompassing the primary tumour and potential microscopic pelvic disease reduces the dose to organs at risk without compromising target coverage. Intensity-modulated radiotherapy is an appropriate definitive treatment for patients with cervical cancer., (Copyright © 2014. Published by Elsevier SAS.)

Background: The optimal model of total dose and fraction size for patients with locally recurrent nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) remains unclear. The authors designed a randomized phase 2 clinical trial to investigate the efficacy of 2 different models, with the objective of determining an optimal model., Methods: Between January 2003 and December 2007, a total of 117 patients with locally recurrent nonmetastatic nasopharyngeal carcinoma were randomized to 2 different models of total dose and fraction size: group A (59 patients) received 60 gray in 27 fractions and group B (58 patients) received 68 gray in 34 fractions. Both groups received 5 daily fractions per week. All patients received IMRT alone., Results: The median follow-up was 25.0 months. The 5-year overall survival in group A was higher than that in group B (44.2% vs 30.3%; P =.06), and the local failure-free survival in group A was slightly lower than that in group B (63.7% vs 71.0%; P =.41). Severe late complications were the main cause of death. The incidences of mucosal necrosis and massive hemorrhage in patients in group B were significantly higher than those among patients in group A at 50.8% versus 28.8% (P =.02) and 31.0% versus 18.6% (P =.12), respectively. Tumor volume (P<.01) and model of total dose and fraction size (P =.03) were found to be significant factors for mucosal necrosis and massive hemorrhage., Conclusions: Appropriately decreasing the total dose and increasing the fraction size can achieve local control similar to that achieved with a higher dose after IMRT; furthermore, it can improve overall survival by significantly reducing the incidence of severe late complications including mucosal necrosis and massive hemorrhage., (© 2014 American Cancer Society.)

Background: The purpose of this study was to determine the effect of adaptive replanning on clinical outcome among patients treated by intensity-modulated radiotherapy (IMRT) for head and neck cancer., Methods: Three hundred seventeen patients underwent IMRT with daily image-guidance for newly diagnosed squamous cell carcinoma of the head and neck to a median dose of 66 Gy (range, 60-74 Gy). Of these 317 patients, 51 (16%) underwent adaptive radiotherapy with modification of the original IMRT midway during treatment., Results: The 2-year local-regional control was 88% for patients treated with adaptive replanning compared with 79% for patients treated without (p = .01). The median time to local-regional recurrence for the 4 patients treated by adaptive radiotherapy was 7 months (range, 3-15 months) with all failures occurring within the high-dose planning target volume (PTV)., Conclusion: Although the use of routine replanning is probably not necessary, our findings do suggest a significant benefit in appropriately selected patients., (© 2014 Wiley Periodicals, Inc.)

Background: The goal of the current study was to assess the rates of recurrence in the neck for patients with lymph node-positive human papillomavirus-associated cancer of the oropharynx who were treated with definitive radiotherapy (with or without chemotherapy)., Methods: This is a single-institution retrospective study. Methodology included database search, and statistical testing including frequency analysis, Kaplan-Meier tests, and comparative tests including chi-square, logistic regression, and log-rank., Results: The cohort consisted of 401 patients with lymph node-positive disease who underwent radiotherapy between January 2006 and June 2012. A total of 388 patients had computed tomography restaging, and 251 had positron emission tomography and/or ultrasound as a component of their postradiation staging. Eighty patients (20%) underwent neck dissection, and 21 patients (26%) had a positive specimen. The rate of neck dissection increased with increasing lymph node stage, and was lower in patients who had positron emission tomography scans or ultrasound in addition to computed tomography restaging. The median follow-up was 30 months. The 2-year actuarial neck recurrence rate was 7% and 5%, respectively, in all patients and those with local control. Lymph node recurrence rates were greater in current smokers (P = .008). There was no difference in lymph node recurrence rates noted between patients who did and those who did not undergo a neck dissection (P = .4) CONCLUSIONS: A treatment strategy of (chemo)radiation with neck dissection performed based on response resulted in high rates of regional disease control in patients with human papillomavirus-associated oropharyngeal cancer., (© 2014 American Cancer Society.)

Background: The purpose of this study was to determine the feasibility of nondaily image-guided radiotherapy (RT) strategies with intensity-modulated radiotherapy (IMRT) for head and neck cancer., Methods: Alignment data was analyzed from 103 consecutive patients treated by IMRT for head and neck cancer who had undergone daily imaging with onboard mega-voltage CT (MVCT), resulting in 3275 images. Geometric setup errors that would have occurred using less-than-daily imaging were hypothetically estimated for 4 temporal less-than-daily image-guided RT protocols., Results: For image-guided RT on the first fraction, weekly image-guided RT, first 5 + weekly image-guided RT, and alternating day image-guided RT, the respective incidences of geometric miss were 50.5%, 33.8%, 30.1%, and 15.7% assuming 3-mm uncertainty margins; and 18.7%, 11.7%, 10.3%, and 4.1% with 5-mm margins., Conclusion: Less-than-daily image-guided RT strategies result in a high incidence of potential miss when 3-mm uncertainty margins are utilized. Less-than-daily image-guided RT strategies should incorporate margins of at least 5 mm., (Copyright © 2013 Wiley Periodicals, Inc.)

Swept source optical coherence tomography (SS-OCT) is a convenient method for precise, early-stage detection of choroidal metastatic lesions, involving assessment of tumor response, and for regular follow-up studies. Using information obtained with SS-OCT, we performed intensity-modulated radiotherapy (IMRT) for a patient with choroidal metastasis from breast cancer with more accuracy than had been previously possible. We made replanning adaptive radiotherapy (ART) three times based on the rapid tumor shrinkage detected by weekly assessments with SS-OCT. Accordingly, the planning target volume (PTV) decreased from 1.6 cm(3) to 0.61 cm(3) (38%), with 0.95 cm(3) (59%) and 0.75 cm(3) (46%) as intermediate values during the treatment course. The D0.1 cm3 of the right optic nerve was also reduced from 1.70 Gy/fraction to 0.69 Gy/faction, with 1.41 Gy/fraction and 1.29 Gy/fraction as intermediate values. Adaptive replanning IMRT made it possible to perform locally curative treatment of the metastatic choroidal lesion with a higher dose for the PTV, and a lower dose for organs at risk (OARs).

Objective: To evaluate the morphological changes of the parotid glands in patients treated with intensity-modulated radiotherapy (IMRT) for nasopharyngeal and oropharyngeal tumors and the correlations with parotid function., Methods: Ten patients with nasopharyngeal and oropharyngeal tumors treated with IMRT between May 2009 and January 2010 at Hokkaido University Hospital were included in this study. In the morphological assessment of the parotid glands, the sizes and computed tomography (CT) numbers of the bilateral parotid glands before and after IMRT with CT were calculated. For functional assessment of the parotid glands, we conducted the Saxon test and used a visual analog scale (VAS) for xerostomia evaluation., Results: Reductions in saliva secretion were observed in the patients treated with IMRT for nasopharyngeal and oropharyngeal tumors, and there was a significant correlation between the reduction in saliva secretion and the VAS. The reductions in the parotid gland size and CT number were larger on the ipsilateral side than on the contralateral side. The reduction in saliva secretion was not significantly correlated with the reduction in parotid gland size, but was significantly correlated with the reduction in CT number., Conclusions: Morphological and functional changes of the parotid glands were observed after IMRT for nasopharyngeal and oropharyngeal tumors, and preservation of the contralateral parotid glands was only partly achieved. Among the morphological changes of the parotid glands, the CT number may be considered a predictor of parotid function after radiotherapy.

Introduction: A comparative study was conducted comparing the difference between (1) conformal radiotherapy (CRT) to the whole breast with sequential boost excision cavity plans and (2) intensity-modulated radiation therapy (IMRT) to the whole breast with simultaneously integrated boost to the excision cavity. The computed tomography (CT) data sets of 25 breast cancer patients were used and the results analysed to determine if either planning method produced superior plans., Methods: CT data sets from 25 past breast cancer patients were planned using (1) CRT prescribed to 50 Gy in 25 fractions (Fx) to the whole-breast planning target volume (PTV) and 10 Gy in 5Fx to the excision cavity and (2) IMRT prescribed to 60 Gy in 25Fx, with 60 Gy delivered to the excision cavity PTV and 50 Gy delivered to the whole-breast PTV, treated simultaneously. In total, 50 plans were created, with each plan evaluated by PTV coverage using conformity indices, plan maximum dose, lung dose, and heart maximum dose for patients with left-side lesions., Results: CRT plans delivered the lowest plan maximum doses in 56% of cases (average CRT = 6314.34 cGy, IMRT = 6371.52 cGy). They also delivered the lowest mean lung dose in 68% of cases (average CRT = 1206.64 cGy, IMRT = 1288.37 cGy) and V20 in 88% of cases (average CRT = 20.03%, IMRT = 21.73%) and V30 doses in 92% of cases (average CRT = 16.82%, IMRT = 17.97%). IMRT created more conformal plans, using both conformity index and conformation number, in every instance, and lower heart maximum doses in 78.6% of cases (average CRT = 5295.26 cGy, IMRT = 5209.87 cGy)., Conclusion: IMRT plans produced superior dose conformity and shorter treatment duration, but a slightly higher planning maximum and increased lung doses. IMRT plans are also faster to treat on a daily basis, with shorter fractionation.