The present study aimed to evaluate whether an adapted plan with Ethos™ could be used for pharyngeal cancer. Ten patients with pharyngeal cancer who underwent chemoradiotherapy with available daily cone-beam computed tomography (CBCT) data were included. Simulated treatments were generated on the Ethos™ treatment emulator using CBCTs every four to five fractions for two plans: adapted and scheduled. The simulated treatments were divided into three groups: early (first-second week), middle (third-fourth week), and late (fifth-seventh week) periods. Dose-volume histogram parameters were compared for each period between the adapted and scheduled plans in terms of the planning target volume (PTV) (D98%, D95%, D50% and D2%), spinal cord (Dmax and D1cc), brainstem (Dmax) and ipsilateral and contralateral parotid glands (Dmedian and Dmean). The PTV D98%, D95% and D2% of the adapted plan were significantly higher than those of the scheduled plans in all periods, except for D98% in the late period. The adapted plan significantly reduced the spinal cord Dmax and D1cc compared with the scheduled plan in all periods. Ipsilateral and contralateral parotid glands Dmean of the adapted plan were lower than those of scheduled plan in the late period. In conclusion, the present study revealed that the adapted plans could maintain PTV coverage while reducing the doses to organs at risk in each period compared with scheduled plans.

PURPOSE: This study aimed to assess recurrence patterns and identify the optimal dose and target volumes of postoperative radiotherapy (PORT) in patients with oral cavity squamous cell carcinoma (OSCC). METHODS: Data of 111 patients who received PORT for OSCC between January 2010 and April 2020 were retrospectively reviewed. The median age was 68 years (range 19-88). PORT was administered as initial treatment to 63 patients and as salvage treatment for recurrent tumors to 48 patients. The median prescribed dose was 60 Gy (range 50-66) administered in 30 fractions (range 25-33). RESULTS: Median follow-up time was 73 months (range 24-147). Overall survival (OS), progression-free survival (PFS), local control (LC), and locoregional control (LRC) at 3 years were 55.6%, 45.6%, 74.6%, and 63.1%, respectively. There were no significant differences in OS, PFS, LC, and LRC between the initially diagnosed and postoperative recurrent cases. Of 22 patients (20%) who developed regional nodal recurrences, 17 (15%) and 11 (10%) had in-field and out-of-field recurrences, respectively. Of 105 patients who received irradiation to the primary tumor bed, 24 (23%) developed recurrence at the primary site. The PFS and LC rates were significantly worse in patients receiving ≤ 56 Gy to the primary site than those receiving > 56 Gy (p = 0.016 and p = 0.032, respectively). CONCLUSION: PORT was effective for postoperative recurrences as well as for initially diagnosed oral cavity cancer. Doses greater than 56 Gy to the primary site may be required in PORT for OSCC.

BACKGROUND: This study aimed to reveal the long-term outcomes and late toxicities (> 5 years) after definitive intensity-modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). METHODS: Data from 43 patients (median age, 55 years; range, 17-72 years) with NPC who underwent definitive IMRT between 2001 and 2018 were analyzed. All patients were alive and disease-free 5 years after IMRT. A total dose of 70 (range, 66-70) Gy was delivered in 35 (33-35) fractions with concurrent cisplatin chemotherapy. RESULTS: The median follow-up duration was 119 (range, 61.5-242.1) months. Three patients developed locoregional failure at 79, 92, and 149 months after IMRT, respectively. Of these, 2 patients died of disease progression at 136 and 153 months after IMRT. One patient died of aspiration pneumonia 141 months after IMRT, despite salvage of the recurrent tumor by re-irradiation. In addition, one patient died of aspiration pneumonia 62 months after the IMRT. Thus, the 10-year overall survival, progression-free survival, and locoregional control rates were 98%, 92%, and 94%, respectively. Grade ≥ 2 and ≥ 3 late toxicities were observed in 28 (65%) and 9 (21%) patients, respectively. Nine second primary cancers, including five tongue cancers and two external auditory canal carcinomas, were observed in seven (16%) patients. CONCLUSION: Late recurrences, severe late toxicities, and second primary cancers were observed > 5 years after IMRT. A long-term follow-up of > 5 years is needed in patients with NPC.

BACKGROUND: We clarified the dose difference between the anisotropic analytical algorithm (AAA) and Acuros XB (AXB) with increasing target's air content using a virtual phantom and clinical cases. MATERIALS AND METHODS: Whole neck volumetric modulated arc therapy (VMAT) plan was transferred into a virtual phantom with a cylindrical air structure at the center. The diameter of the air structure was changed from 0 to 6 cm, and the target's air content defined as the air/planning target volume (PTV) in percent (air/PTV) was varied. VMAT plans were recalculated by AAA and AXB with the same monitor unit (MU) and multi-leaf collimator (MLC) motions. The dose at each air/PTV (5%-30%) was compared between each algorithm with D98%, D95%, D50% and D2% for the PTV. In addition, MUs were also compared with the same MLC motions between the D95% prescription with AAA (AAA_D95%), AXB_D95%, and the prescription to 100% minus air/PTV (AXB_D100%-air/PTV) in clinical cases of head and neck (HNC). RESULTS: When air/PTV increased (5-30%), the dose differences between AAA and AXB for D98%, D95%, D50% and D2% were 3.08-15.72%, 2.35-13.92%, 0.63-4.59%, and 0.14-6.44%, respectively. At clinical cases with air/PTV of 5.61% and 28.19%, compared to AAA_D95%, the MUs differences were, respectively, 2.03% and 6.74% for AXB_D95% and 1.80% and 0.50% for AXB_D100%-air/PTV. CONCLUSION: The dose difference between AAA and AXB increased as the target's air content increased, and AXB_D95% resulted in a dose escalation over AAA_D95% when the target's air content was ≥ 5%. The D100%-air/PTV of PTV using AXB was comparable to the D95% of PTV using AAA.

PURPOSE: To investigate the risk of bladder cancer (BCa) in patients treated with brachytherapy for prostate cancer (PCa). METHODS: We retrospectively analyzed 583 patients with PCa who underwent brachytherapy with or without external beam radiotherapy (EBRT). We analyzed the disease-free survival (DFS) of BCa in patients with PCa who underwent brachytherapy with or without EBRT. We performed multivariate Cox regression analyses of DFS using age, EBRT, and Brinkman index (BI) score (number of cigarettes smoked per day × number of years smoking) ≥ 200 as variables for BCa after brachytherapy. RESULTS: Fourteen patients (2.4%) developed BCa after brachytherapy with or without EBRT. The percentage of high-grade urothelial carcinoma (UC) was 63.6%. A total of 85.7% of patients had non-muscle invasive BCa, and 14.3% of patients had muscle invasive BCa. DFS was longer in brachytherapy monotherapy than in combination therapy (brachytherapy + EBRT). Multivariate Cox regression analysis showed that a BI score ≥ 200 (Hazard Ratio (HR 8.61; 95% Confidence Interval (CI) 1.12-65.98) and EBRT combination (HR 3.29; 95% CI 1.03-10.52) were significantly associated with BCa development in patients with PCa treated with brachytherapy. Furthermore, patients with BI score ≥ 200 and EBRT combination had a significantly higher risk of BCa compared with patients with BI score < 200 (HR Log-rank test P = 0.010). CONCLUSION: Most cases of BCa after brachytherapy with or without EBRT are high grade and invasive. We hypothesized that the EBRT combination might be a risk factor for BCa in patients with PCa who underwent brachytherapy.

BACKGROUND AND PURPOSE: In this study, fluoromisonidazole positron emission tomography (F-MISO PET/CT) was used to evaluate tumor hypoxia and re-oxygenation in patients with lung tumors treated with stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: Patients with T1-2 N0 lung cancer were included in this study. The prescribed dose was 48-52 Gy in four fractions. F-MISO PET/CT was performed twice, before SBRT and 1-3 days after the first irradiation. The maximum standardized uptake value (SUVmax) and tumor/muscle ratio (TMR) were evaluated as indicators of hypoxia. The threshold for hypoxia was defined as a TMR of 1.30 or more. RESULTS: Between 2016 and 2021, 15 patients were included. Pre-treatment tumor hypoxia was observed in nine tumors (60 %). TMR in all six tumors without pre-treatment hypoxia rose after single high-dose irradiation. In contrast, TMR in six of nine tumors with pre-treatment hypoxia dropped after irradiation, suggesting re-oxygenation. Although no local recurrence was noted, regional and/or distant relapses were seen in four patients (27 %). Of these, three had tumors with abnormal F-MISO uptake. The remaining patient had a tumor without signs of hypoxia on pre-treatment PET/CT. The 2-year progression free survival of patients with tumors with and without pre-treatment hypoxia were 30 % and 63 %, respectively (p = 0.319). CONCLUSION: Tumor hypoxia reduced after single high-dose irradiation. Tumor with F-MISO uptake seems to be an unfavorable prognostic factor in lung SBRT.

PURPOSE: Stereotactic body radiotherapy (SBRT) is a treatment option for early-stage lung cancer. We aimed to examine the differences in failure patterns after SBRT according to the clinical T stage. METHODS: A total of 120 patients with early-stage lung cancer (T1-3N0M0) who underwent SBRT were analysed. The clinical stage in patients whose tumours were in contact with the chest wall was confirmed using four-dimensional computed tomography (4D-CT). Local failure, regional node metastasis, and distant metastasis were confirmed from clinical charts. RESULTS: Median follow-up time was 27.5 months (range 7-122) after SBRT. Thirteen patients were restaged from clinical T2 with visceral pleural invasion to T3 with chest wall invasion using 4D-CT analysis. Thirty-seven patients developed recurrences. The median progression-free survival (PFS) and overall survival (OS) were 38.1 and 53.8 months, respectively. The 3‑year PFS and OS rates were 50.7% and 60.3%, respectively. A significant difference was observed in PFS according to the clinical T stage (p = 0.001). No significant differences were observed in OS according to the clinical T stage (p = 0.213). The proportion of locoregional failures relative to distant metastasis decreased with progression from T1 to T3. The pleural dissemination rate was significantly higher in T3 tumours than in T1 and T2 tumours (p = 0.010). CONCLUSION: Clinical T stage is associated with PFS after SBRT for lung cancer. There were differences in the failure patterns according to T stage. 4D-CT might provide significant information for assessing chest wall invasion associated with unfavourable PFS.

BACKGROUND: JCOG1015A1 is an ancillary research study to determine the organ-specific dose constraints in head and neck carcinoma treated with intensity-modulated radiation therapy (IMRT) using data from JCOG1015. METHODS: Individual patient data and dose-volume histograms of organs at risk (OAR) were collected from 74 patients with nasopharyngeal carcinoma treated with IMRT who enrolled in JCOG1015. The incidence of late toxicities was evaluated using the cumulative incidence method or prevalence proportion. ROC analysis was used to estimate the optimal DVH cut-off value that predicted toxicities. RESULTS: The 5-year cumulative incidences of Grade (G) 1 myelitis, ≥ G1 central nervous system (CNS) necrosis, G2 optic nerve disorder, ≥ G2 dysphagia, ≥ G2 laryngeal edema, ≥ G2 hearing impaired, ≥ G2 middle ear inflammation, and ≥ G1 hypothyroidism were 10%, 5%, 2%, 11%, 5%, 26%, 34%, and 34%, respectively. Significant associations between DVH parameters and incidences of toxicities were observed in the brainstem for myelitis (D1cc ≥ 55.8 Gy), in the brain for CNS necrosis (D1cc ≥ 72.1 Gy), in the eyeball for optic nerve disorder (Dmax ≥ 36.6 Gy), and in the ipsilateral inner ear for hearing impaired (Dmean ≥ 44 Gy). The optic nerve, pharyngeal constrictor muscle (PCM), and thyroid showed tendencies between DVH parameters and toxicity incidence. The prevalence proportion of G2 xerostomia at 2 years was 17 versus 6% (contralateral parotid gland Dmean ≥ 25.8 Gy vs less). CONCLUSIONS: The dose constraint criteria were appropriate for most OAR in this study, although more strict dose constraints might be necessary for the inner ear, PCM, and brainstem.

Stereotactic body radiotherapy (SBRT) is a treatment option for early-stage lung cancer. The purpose of this study was to investigate the optimal dose distribution and prognostic factors for local control (LC) after SBRT for lung cancer. A total of 104 lung tumors from 100 patients who underwent SBRT using various treatment regimens were analyzed. Dose distributions were corrected to the biologically effective dose (BED). Clinical and dosimetric factors were tested for association with LC after SBRT. The median follow-up time was 23.8 months (range, 3.4-109.8 months) after SBRT. The 1- and 3-year LC rates were 95.7% and 87.7%, respectively. In univariate and multivariate analyses, pathologically confirmed squamous cell carcinoma (SQ), T2 tumor stage, and a Dmax < 125 Gy (BED10) were associated with worse LC. The LC rate was significantly lower in SQ than in non-SQ among tumors that received a Dmax < 125 Gy (BED10) (p = 0.016). However, there were no significant differences in LC rate between SQ and non-SQ among tumors receiving a Dmax ≥ 125 Gy (BED10) (p = 0.198). To conclude, SQ, T2 stage, and a Dmax < 125 Gy (BED10) were associated with poorer LC. LC may be improved by a higher Dmax of the planning target volume.

BACKGROUND: The present study aimed to evaluate the prognostic factors in human papillomavirus (HPV)-positive and HPV-negative oropharyngeal cancer (OPC) treated with definitive radiotherapy. METHODS: We retrospectively evaluated 101 patients with OPC who underwent definitive radiotherapy between 2008 and 2018. RESULTS: The median follow-up period of the surviving patients was 68 months (range, 8-164 months). The 5-year overall survival rate was 69.8%. Univariate analyses revealed that poor survival was associated with male sex, smoking ≥30 pack-years, Eastern Cooperative Oncology Group performance status ≥1, tumor-node-metastasis (TNM) stage III-IV (8th edition), HPV-negativity, serum lactate dehydrogenase (LDH) ≥202, C-reactive protein/albumin ratio ≥0.15, and lymphocyte-to-monocyte ratio <2.90. In multivariate analyses, poor survival was independently correlated with smoking ≥30 pack-years (p < 0.01) and LDH ≥202 (p = 0.02). CONCLUSIONS: The present study suggested that high LDH levels predicted poor survival after definitive radiotherapy for patients with both HPV-positive and HPV-negative OPC.

BACKGROUND: The role of intensity-modulated radiation therapy in the treatment of cervical esophageal cancer remains unclear. The outcome of concurrent chemoradiotherapy for cervical esophageal squamous cell carcinoma using intensity-modulated radiation therapy was retrospectively evaluated. METHODS: Between 2004 and 2017, 36 patients with cervical esophageal cancer treated with intensity-modulated radiation therapy were included. Among these patients, one had stage II disease, three stage III, 19 stage IVA, and 13 stage IVB. All patients received radiotherapy at a dose of 60 Gy and concurrent platinum-based doublet chemotherapy. RESULTS: The median follow-up period for surviving patients was 36 months. Three-year locoregional control, progression-free survival, and overall survival rates were 54, 40, and 46%, respectively. Disease progression was noted in 20 out of 36 patients (56%). Grade 3 late toxicities were observed in four patients (three esophageal stenoses and one carotid artery stenosis). There were no grade 4-5 toxicities. Univariate analysis identified the duration of radiotherapy as a prognostic factor for overall survival. CONCLUSIONS: Chemoradiotherapy using intensity-modulated radiation therapy for locally advanced cervical esophageal carcinoma achieved satisfactory locoregional control and survival with acceptable toxicities.

PURPOSE: We investigated the performance of the simplified knowledge-based plans (KBPs) in stereotactic body radiotherapy (SBRT) with volumetric-modulated arc therapy (VMAT) for lung cancer. MATERIALS AND METHODS: For 50 cases who underwent SBRT, only three structures were registered into knowledge-based model: total lung, spinal cord, and planning target volume. We performed single auto-optimization on VMAT plans in two steps: 19 cases used for the model training (closed-loop validation) and 16 new cases outside of training set (open-loop validation) for TrueBeam (TB) and Halcyon (Hal) linacs. The dosimetric parameters were compared between clinical plans (CLPs) and KBPs: CLPclosed, KBPclosed-TB and KBPclosed-Hal in closed-loop validation, CLPopen, KBPopen-TB and KBPopen-Hal in open-loop validation. RESULTS: All organs at risk were comparable between CLPs and KBPs except for contralateral lung: V5 of KBPs was approximately 3%-7% higher than that of CLPs. V20 of total lung for KBPs showed comparable to CLPs; CLPclosed vs. KBPclosed-TB and CLPclosed vs. KBPclosed-Hal: 4.36% ± 2.87% vs. 3.54% ± 1.95% and 4.36 ± 2.87% vs. 3.54% ± 1.94% (P = 0.54 and 0.54); CLPopen vs. KBPopen-TB and CLPopen vs. KBPopen-Hal: 4.18% ± 1.57% vs. 3.55% ± 1.27% and 4.18% ± 1.57% vs. 3.67% ± 1.26% (P = 0.19 and 0.27). CI95 of KBPs with both linacs was superior to that of the CLP in closed-loop validation: CLPclosed vs. KBPclosed-TB vs. KBPclosed-Hal: 1.32% ± 0.12% vs. 1.18% ± 0.09% vs. 1.17% ± 0.06% (P < 0.01); and open-loop validation: CLPopen vs. KBPopen-TB vs. KBPopen-Hal: 1.22% ± 0.09% vs. 1.14% ± 0.04% vs. 1.16% ± 0.05% (P ≤ 0.01). CONCLUSIONS: The simplified KBPs with limited number of structures and without planner intervention were clinically acceptable in the dosimetric parameters for lung VMAT-SBRT planning.

BACKGROUND/AIM: We evaluated the dosimetric profiles of manually generated volumetric-modulated arc therapy (VMAT) plans and performance of a commercial knowledge-based planning system (KBP) in treating breast cancer. MATERIALS AND METHODS: We defined the manually generated VMAT plan as the manual plan (MP). Twenty MPs were generated for left-sided breast cancer patients who underwent breast-conserving surgery and used to develop a KBP training set. The other five patients were used for validation. The dosimetric parameters among MPs, tangential irradiation plans (TPs), and KBP-VMAT plans (KBP-Ps) were compared. RESULTS: D95 and homogeneity of the planning target volume (PTV) were significantly higher and greater in MPs and KBP-Ps than in TPs. Lung V20, V40 The Dmean for the left anterior descending artery was lower in MPs and KBP-Ps than in TPs. KBP could save time in generating VMAT plans. CONCLUSION: MPs and KBP-Ps could ensure higher dose uniformity of PTV than TPs. KBP could faster generate comparable MPs for breast cancer.

PURPOSE: This study aimed to investigate the influence of cleaned-up knowledge-based treatment planning (KBP) models on the plan quality for volumetric-modulated arc therapy (VMAT) of prostate cancer. MATERIALS AND METHODS: Thirty prostate cancer VMAT plans were enrolled and evaluated according to four KBP modeling methods as follows: (1) model not cleaned - trained by fifty other clinical plans (KBPORIG); (2) cases cleaned by removing plans that did not meet all clinical goals of the dosimetric parameters, derived from dose-volume histogram (DVH) (KBPC-DVH); (3) cases cleaned outside the range of ±1 standard deviation through the principal component analysis regression plots (KBPC-REG); and (4) cases cleaned using both methods (2) and (3) (KBPC-ALL). Rectal and bladder structures in the training models numbered 34 and 48 for KBPC-DVH, 37 and 33 for KBPC-REG, and 26 and 33 for KBPC-ALL, respectively. The dosimetric parameters for each model with one-time auto-optimization were compared. RESULTS: All KBP models improved target dose coverage and conformity and provided comparable sparing of organs at risks (rectal and bladder walls). There were no significant differences in plan quality among the KBP models. Nevertheless, only the KBPC-ALL model generated no cases of >1% V78 Gy (prescribed dose) to the rectal wall, whereas the KBPORIG, KBPC-DVH, and KBPC-REG models included two, four, and three cases, respectively, which were difficult to overcome with KBP because the planning target volume (PTV) and rectum regions overlapped. CONCLUSIONS: The cleaned-up KBP model based on DVH and regression plots improved plan quality in the PTV-rectum overlap region.

BACKGROUND: We retrospectively compared the 7th and the 8th editions of The American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM classification in the cohort of survival of the patients with esophageal squamous cell carcinoma (ESCC) treated by definitive radiotherapy. METHODS: We included in this study 403 patients with ESCC who underwent radiotherapy or chemoradiotherapy, at a total radiation dose of ≥ 50 Gy with curative intent from 2000 to 2016 at Kindai University Hospital, and who had no distant metastasis (excluding supraclavicular lymph node). The same patient data set was re-staged according to both the 7th and 8th editions of AJCC/UICC TNM classification. RESULTS: For the 7th edition, 5-year overall survival (OS) for stages I, II, III, and IV were 58%, 52%, 22%, and 12%, respectively, which seemed to be separable into two groups (Stages I-II and III-IV). In the 8th edition, corresponding values for stages I, II, III, and IV were 65%, 44%, 34%, and 16%, respectively, which seemed to be separated into three groups (Stage I, II-III, and IV). CONCLUSIONS: The 8th edition of AJCC/UICC TNM classification is a useful predictor of OS among ESCC patients who were treated with definitive radiotherapy.

This study aimed to identify factors that predict prognosis after radiotherapy for brain metastases (BMs) from small-cell lung cancer (SCLC). This study retrospectively evaluated 48 consecutive patients who underwent whole-brain radiotherapy (WBRT) for BMs from SCLC between February 2008 and December 2017. WBRT was delivered at a median dose of 30 Gy (range: 30-40 Gy) in 10 fractions (range: 10-16 fractions). Clinical factors were tested for associations with overall survival after WBRT. The median survival and 1-year overall survival rate after WBRT treatment were 232 days and 34.4%, respectively. Univariate analyses revealed that longer survival was associated with Eastern Cooperative Oncology Group performance status of 0-1, asymptomatic BMs, lactate dehydrogenase (LDH) in the normal range, Radiation Therapy Oncology Group-recursive partitioning analysis class 2, and a graded prognostic assessment score of ≥1.5 (P < 0.01, P < 0.01, P < 0.01, P < 0.01 and P < 0.05, respectively). In the multivariate analyses, longer survival was independently associated with asymptomatic BMs [hazard ratio for death (HR), 0.32; 95% confidence interval (CI), 0.12-0.79; P < 0.05] and LDH in the normal range (HR, 0.42; 95% CI, 0.21-0.83; P < 0.05). The presence of symptoms due to BMs and LDH values independently predicted prognosis after WBRT for BMs from SCLC. Elevated LDH may provide valuable information for identifying patients with BMs who could have poor survival outcomes.

Aim: This study aimed to identify prognostic factors for response to whole-brain radiotherapy (WBRT) in patients with brain metastases (BMs) from non-small cell lung cancer (NSCLC). Patients and Methods: This study retrospectively evaluated 100 patients who underwent WBRT for BMs from NSCLC between December 2012 and October 2017. Clinical factors were tested for associations with overall survival after WBRT. Results: The median follow-up time was 134 days (range=14-1,395 days), the median survival time was 143 days, and the 1-year survival rate was 30.4%. Univariate and multivariate analyses revealed that better survival was independently associated with expression of programmed death-ligand 1 (PD-L1), no previous treatment for BMs, no extracranial disease, and a neutrophil-to-lymphocyte ratio (NLR) of <5.0. Conclusion: A low NLR and positive PD-L1 expression independently predict better prognosis in patients with BMs from NSCLC after WBRT. These findings suggest that the potential immune response may influence survival among patients with BMs.

[This corrects the article DOI: 10.1371/journal.pone.0204721.].

BACKGROUND: Chemoradiotherapy (CRT) is a standard treatment for anal canal cancer although many patients with anal canal cancer undergo surgery in Japan. The efficacy of CRT for anal canal cancer was evaluated retrospectively. METHODS: Medical charts of 13 patients with anal canal cancer treated by definitive CRT from October 2004 to May 2016 were reviewed. Twelve patients had squamous cell carcinoma and one had adeno-squamous carcinoma. PET/CT simulation was performed in nine patients. The median total dose was 59.4 Gy (range 57.6-63.4 Gy) with fractions of 1.8-2.0 Gy. Ten patients received chemotherapy with mitomycin C (10 mg/m2) and fluorouracil (5-FU) (800 mg/m2 over 4 days) in weeks 1 and 5, while two patients were treated with cisplatin (40 mg) and 5-FU (750 mg over 5 days) in weeks 1 and 5. One elderly patient received radiotherapy (RT) alone. RESULTS: All 13 patients were alive after a median follow-up period of 102 months (range 16-121 months). Local failure only occurred in the patient with adeno-squamous cell carcinoma, while there was no loco-regional recurrence or distant metastasis in the other 12 patients. The 5-year loco-regional control rate (LRC) and 5-year overall survival rate (OS) were 92% and 100%, respectively. Acute toxicities of ≥ grade 3 were observed in six patients (46%), mainly being dermatitis around the anal verge, and late toxicity of ≥ grade 3 occurred in one patient. CONCLUSION: CRT for squamous cell carcinoma of the anal canal achieved good LRC and OS with acceptable toxicities.

BACKGROUND: This study clarified the mechanical performance of volumetric modulated arc therapy (VMAT) plans for prostate cancer generated with a commercial knowledge-based treatment planning (KBP) and whether KBP system could be applied clinically without any major problems with mechanical performance. METHODS: Thirty consecutive prostate cancer patients who underwent VMAT using extant clinical plans were evaluated. The mechanical performance and dosimetric accuracy of the single optimized KBPs, which were trained with other 51 clinical plans, were compared with the clinical plans. The mechanical performance metrics were mean field area (MFA), mean asymmetry distance (MAD), cross-axis score (CAS), closed leaf score (CLS), small aperture score (SAS), leaf travel (LT), modulation complexity score (MCSv), and monitor unit (MU). The γ passing rates were evaluated with ArcCheck and EBT3 film. RESULTS: The mean mechanical performance metrics (clinical plan vs. KBP) were as follows: 18.28 cm2 vs. 17.25 cm2 (MFA), 21.08 mm vs. 20.47 mm (MAD), 0.54 vs. 0.55 (CAS), 0.040 vs. 0.051 (CLS), 0.20 vs. 0.23 (SAS5mm), 458.5 mm vs. 418.8 mm (LT), 0.27 vs. 0.27 (MCSv), and 618.2 vs. 622.1 (MU), respectively. Significant differences were observed for CLS and LT. The average γ passing rates (clinical plan vs. KBP) were as follows: 99.0% vs. 99.1% (3%/3 mm) and 92.4% vs. 92.5% (2%/2 mm) with ArcCHeck, and 99.5% vs. 99.4% (3%/3 mm) and 95.2% vs. 95.4% (2%/2 mm) with EBT3 film, respectively. CONCLUSIONS: The KBP used lower multileaf collimator (MLC) travel and more closed or small MLC apertures than the clinical plan. The KBP system of VMAT for the prostate cancer was acceptable for clinical use without any major problems.

Tungsten functional paper (TFP) is a paper-based radiation-shielding material, which is lead-free and easy to cut. We developed a radiation protection undergarment using TFP for prostate cancer patients treated with permanent 125I seed implantation (PSI). The aim of this study was to evaluate the shielding ability of the undergarment with respect to household contacts and members of the public. Between October 2016 and April 2017, a total of 10 prostate cancer patients treated with PSI were enrolled in this prospective study. The external radiation exposure from each patient 1 day after PSI was measured with and without the undergarment. Measurements were performed using a survey meter at 100 cm from the surface of the patient's body. The exposure rates were measured from five directions: anterior, anteriorly oblique, lateral, posteriorly oblique, and posterior. The measured radiation exposure rates without the undergarment, expressed as mean ± standard deviation, from the anterior, anteriorly oblique, lateral, posteriorly oblique, and posterior directions were 1.28 ± 0.43 μSv/h, 0.70 ± 0.34 μSv/h, 0.21 ± 0.062 μSv/h, 0.65 ± 0.33 μSv/h and 1.24 ± 0.41 μSv/h, respectively. The undergarment was found to have (mean ± standard deviation) shielding abilities of 88.7 ± 5.8%, 44.0 ± 42.1%, 50.6 ± 15.9%, 72.9 ± 27.0% and 90.4 ± 10.7% from the anterior, anteriorly oblique, lateral, posteriorly oblique, and posterior directions, respectively. In conclusion, this shielding undergarment is a useful device that has the potential to reduce radiation exposure for the general public and the patient's family.

BACKGROUND/AIM: 18F-misonidazole positron emission tomography (FMISO PET)/computed tomography (CT) obtained before and during radiotherapy (RT) was analyzed as to whether it could predict clinical outcome. PATIENTS AND METHODS: Twenty-two patients were included. FMISO PET/ CT was performed twice before RT and at a dose of approximately 20 Gy/10 fractions. FMISO maximum standardized uptake values (SUVmax), the tumor-to-muscle ratios (T/M), and hypoxic volume (HV) in gross target volumes were measured. RESULTS: Of the 22 tumors, 18 had hypoxic areas (SUVmax ≥1.60) before RT. SUVmax, T/M, and HV on the first PET/CT were significantly correlated with initial tumor response, although the values during RT were not related to the response. The overall survival and loco-regional control rates of patients below cut-off values were significantly better than those above the cut-off values. CONCLUSION: Tumor hypoxia detected by FMISO PET/CT before RT may predict clinical outcome.

BACKGROUND: Four-dimensional computed tomography (4D-CT) ventilation is an emerging imaging modality. Functional avoidance of regions according to 4D-CT ventilation may reduce lung toxicity after radiation therapy. This study evaluated associations between 4D-CT ventilation-based dosimetric parameters and clinical outcomes. METHODS: Pre-treatment 4D-CT data were used to retrospectively construct ventilation images for 40 thoracic cancer patients retrospectively. Fifteen patients were treated with conventional radiation therapy, 6 patients with hyperfractionated radiation therapy and 19 patients with stereotactic body radiation therapy (SBRT). Ventilation images were calculated from 4D-CT data using a deformable image registration and Jacobian-based algorithm. Each ventilation map was normalized by converting it to percentile images. Ventilation-based dosimetric parameters (Mean Dose, V5 [percent lung volume receiving ≥5 Gy], and V20 [percent lung volume receiving ≥20 Gy]) were calculated for highly and poorly ventilated regions. To test whether the ventilation-based dosimetric parameters could be used predict radiation pneumonitis of ≥Grade 2, the area under the curve (AUC) was determined from the receiver operating characteristic analysis. RESULTS: For Mean Dose, poorly ventilated lung regions in the 0-30% range showed the highest AUC value (0.809; 95% confidence interval [CI], 0.663-0.955). For V20, poorly ventilated lung regions in the 0-20% range had the highest AUC value (0.774; 95% [CI], 0.598-0.915), and for V5, poorly ventilated lung regions in the 0-30% range had the highest AUC value (0.843; 95% [CI], 0.732-0.954). The highest AUC values for Mean Dose, V20, and V5 were obtained in poorly ventilated regions. There were significant differences in all dosimetric parameters between radiation pneumonitis of Grade 1 and Grade ≥2. CONCLUSIONS: Poorly ventilated lung regions identified on 4D-CT had higher AUC values than highly ventilated regions, suggesting that functional planning based on poorly ventilated regions may reduce the risk of lung toxicity in radiation therapy.

Purpose: The aim of this study was to compare the implant quality between intraoperatively built custom-linked seeds (IBCL) and loose seeds (LS) retrospectively. Material and methods: This study included 74 prostate cancer patients who were treated with permanent prostate brachytherapy (PPB) using IBCL (n = 37) or LS (n = 37) between July 2014 and June 2016. Dose-volume histogram (DVH) parameters, seed migration, and operation time were compared between the IBCL and LS groups. In addition to the standard target volume of the whole prostate gland, DVH parameters for prostate plus a 3 mm margin (CTV) were evaluated. Results: In intraoperative planning, prostate V150 was lower (54.8% vs. 59.6%, p = 0.027), and CTV V100 (88.1% vs. 85.6%, p = 0.019) and D90 (98.5% vs. 92.6%, p = 0.0033) were higher in the IBCL group compared with in the LS group. In post-implant dosimetry, prostate V100 (96.9% vs. 95.2%, p = 0.020), CTV V100 (85.6% vs. 81.7%, p = 0.046), and CTV D90 (94.2% vs. 86.5%, p < 0.001) were higher, and prostate V150 (57.1% vs. 64.5%, p = 0.0051) and CTV V150 (31.5% vs. 35.7%, p = 0.046) were lower in the IBCL group compared with in the LS group. Regarding DVH changes between intraoperative planning and post-implant dosimetry, the decrease in prostate D90 was significantly lower in the IBCL group than in the LS group (-1.16% vs. -4.17%, p < 0.001). For the IBCL group, the operation time was slightly but significantly longer than that for the LS group (50.5 minutes vs. 43.7 minutes, p = 0.011). However, the seed migration rate was significantly lower in the IBCL group than in the LS group (5% vs. 41%, p < 0.001). Conclusions: Intraoperatively built custom-linked is more advantageous than LS in terms of dosimetric parameters and migration.

本研究は、日本臨床腫瘍研究グループ（JCOG）で行った「上咽頭癌に対する強度変調放射線治療（IMRT）の多施設共同第II相試験（JCOG1015）」の線量体積ヒストグラム（DVH）と患者データを用いて、晩期有害事象と正常臓器の線量効果関係を明らかにする研究である。本研究は2020年8月にJCOGプロトコール審査委員会で承認され、さらに2020年に9月に近畿大学医学部で、2021年2月に国立研究開発法人国立がん研究センターの倫理委員会で承認された。 2021年度には、これらのデータを基に、内耳Dmean（平均線量)、甲状腺Dmean、水晶体Dmean、眼球Dmax（最大線量）、視神経Dmax、耳下腺Dmedian（中央線量）, 耳下腺Dmean、中下咽頭収縮筋Dmean、喉頭Dmean、頸髄Dmax, 頸髄D1cc（1cc線量）、脳Dmax, 脳D1cc、脳幹Dmax, 脳幹D1ccなどのDVH因子と臓器特異的晩期有害事象との線量効果関係を検討した。その結果、脊髄炎G1以上と脳幹D1cc≧55.8Gy、中枢神経壊死G1以上と脳D1cc≧72.1Gy、聴覚障害G2以上と内耳Dmean≧44Gy、および中耳炎G2以上と内耳Dmean≧51.5Gyとの間に有意な線量依存関係が確認された。また、嚥下障害G2以上と中下咽頭収縮筋Dmean ≧41.2Gy、および甲状腺機能低下G1以上と甲状腺Dmean ≧45.6Gyとの間に線量依存傾向がみられた。JCOG1015では聴覚障害・中耳炎、脊髄炎の頻度が比較的高く、内耳および脳幹線量との相関が見られたため、内耳、脳幹線量のさらなる低減が望ましいと考えられた。以上の結果は、2021年11月にオンライン開催された第34回日本放射線腫瘍学会で発表した。その後、英文原著論文として執筆中である。

適応放射線治療の介入時期を明らかにするため、治療室内CT(CBCT)を用いた前向き臨床試験を行った。5週間の間に耳下腺の体積減少が見られた。標的体積も体積減少をみとめたが、線量低下はなかった。脊髄・脳幹の最大線量は2週目から約1割程度で5%以上の増加がみられ、再治療計画が必要と考えられた。人工知能を利用したknowledge-based planning (KBP)は、再治療計画の迅速化に有効である。前立腺癌および頭頸部癌に対して、KBPの治療計画と実際に照射された治療計画との比較を行った。いずれの検討でも、KBPで作成したプランは、実臨床で用いられた治療計画と同等あるいは優れていた。