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The role of adjuvant external-beam radiotherapy (EBRT) in the treatment of locally advanced papillary thyroid carcinoma (PTC) remains controversial due to the lack of prospective data and the conflicting retrospective data. This study aimed to determine the benefits of adjuvant EBRT in patients with PTC and other organ invasions using propensity score matching to reduce the heterogeneity of the patient population.Data from patients with PTC with other organ invasions but no distant metastases who underwent surgery and adjuvant radioactive iodine (RAI) alone (Non-EBRT group) or adjuvant EBRT plus RAI (EBRT group) were retrospectively reviewed. Propensity matching was used to reduce heterogeneity. Survival outcomes and toxicities associated with EBRT were evaluated.Between January 2005 and December 2019, 102 patients in the Non-EBRT group and 26 patients in the EBRT group were evaluated. In the 48 propensity score-matched patients, no significant differences in baseline characteristics between the Non-EBRT and EBRT groups were detected. The locoregional recurrence-free survival (LRRFS) and recurrence-free survival (RFS) rates were significantly higher in the EBRT group compared with the rates in the Non-EBRT group (5y-LRRFS: 100% vs. 74%, p = 0.003, 5y-RFS: 91% vs. 74%, p = 0.035). EBRT was well-tolerated, with no grade ≥ 3 toxicity, and all patients completed the therapy as planned.Adjuvant EBRT plus RAI exhibited acceptable toxicity and improved LRRFS and RFS in patients with PTC with other organ invasions compared with RAI alone.

There is a lack of data on combined radiotherapy (RT) and cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) risk factors and toxicity. This study aimed to assess the incidence of and risk factors for non-hematologic toxicities in patients treated with combined RT and CDK4/6i using dose-volume parameter analysis.We conducted a retrospective multicenter cohort study of patients with metastatic breast cancer receiving RT within 14 days of CDK4/6i use. The endpoint was non-hematologic toxicities. Patient characteristics and RT treatment planning data were compared between the moderate or higher toxicities (≥ grade 2) group and the non-moderate toxicities group.Sixty patients were included in the study. CDK4/6i was provided at a median daily dose of 125 mg and 200 mg for palbociclib and abemaciclib, respectively. In patients who received concurrent RT and CDK4/6i (N = 29), the median concurrent prescribed duration of CDK4/6i was 14 days. The median delivered RT dose was 30 Gy and 10 fractions. The rate of grade 2 and 3 non-hematologic toxicities was 30% and 2%, respectively. There was no difference in toxicity between concurrent and sequential use of CDK4/6i. The moderate pneumonitis group had a larger lung V20 equivalent dose of 2 Gy per fraction and planning target volume than the non-moderate pneumonitis group.Moderate toxicities are frequent with combined RT and CDK4/6i. Caution is necessary concerning the combined RT and CDK4/6i. Particularly, reducing the dose to normal organs is necessary for combined RT and CDK4/6i.

Papillary thyroid carcinoma (PTC) with other organ invasions is directly related to patient prognosis and quality of life; however, studies on the clinical outcomes of adjuvant radioactive iodine (RAI) for PTC with other organ invasions are limited. This study aimed to clarify the clinical outcomes and prognostic factors for patients with PTC with other organ invasions after adjuvant RAI.Patients with PTC with other organ invasions without distant metastases who underwent surgery and adjuvant RAI were retrospectively reviewed. We evaluated the initial responses based on the American Thyroid Association guidelines and survival rates. Prognostic factors for locoregional recurrence-free survival (LRRFS) were analyzed.Between January 2005 and December 2019, 102 patients were included in the study. Their median age was 55 years. The median follow-up duration was 92 months (range; 30-231 months). The excellent response rate after RAI was 42%. The 7-year overall survival, LRRFS, and recurrence-free survival rates were 100%, 75%, and 75%, respectively. Metastatic lymph node size, resection margin status, and post-RAI suppressed thyroglobulin level were the independent prognostic factors for LRRFS.We demonstrated that 75% of patients with PTC with other organ invasions could achieve long-term survival without recurrence after adjuvant RAI. Future development of effective treatment strategies for large metastatic lymph nodes, gross residual tumors, and high serum thyroglobulin levels is warranted.

We investigated the localization accuracy of the off-isocenter targets using SyncTraX FX4, a new image registration device.In a phantom study, we used a MultiMet-WL Cube with metal targets at different distances from the isocenter. Image registrations were performed with SyncTraX and cone-beam computed tomography (CBCT). Nineteen fields with different gantry, collimator, and couch angles were delivered to each target. Localization errors of the off-isocenter targets were then evaluated. In a clinical study, localization accuracy was evaluated for 32 patients. First, image registration was performed using SyncTraX, and the accuracy of patient positioning was evaluated using CBCT. Next, positioning corrections were performed for intracranial setup errors exceeding the threshold (0.5 mm/0.5°) in each field. Finally, total setup uncertainty was evaluated using CBCT. Differences in dosimetric errors from planned doses between no patient positioning corrections during treatment and positioning corrections with SyncTraX were also evaluated.In the phantom study, the positioning accuracy on targets up to 7 cm from the isocenter was within 1 mm. In the clinical practice, the localization accuracies of SyncTraX were 0.35 ± 0.39 mm, 0.30 ± 0.24 mm, and 0.03 ± 0.27 mm in the lateral, vertical, and longitudinal directions, respectively. Post-treatment setup errors were reduced by correcting intrafractional setup errors with SyncTraX during treatment. Positioning corrections with SyncTraX reduced the maximum dosimetric error from 1.6% to 1.0%.SyncTraX provides satisfactory localization accuracy for the off-isocenter targets within 7 cm. SyncTraX reduce dosimetric errors caused by intrafractional setup errors during treatment.

Objective Compared with the implementation speed of image-guided adaptive brachytherapy for uterine cervical cancer, that of intracavitary and interstitial brachytherapy is slow, possible because it requires more invasive procedure of inserting needles directly into tumours. To accelerate the implementation speed of intracavitary and interstitial brachytherapy, a first hands-on seminar for image-guided adaptive brachytherapy and intracavitary and interstitial brachytherapy for uterine cervical cancer was held on 26 November 2022, supported by Japanese Society for Radiology and Oncology. This article deals with this hands-on seminar and difference of degree of confidence of participants in starting intracavitary and interstitial brachytherapy before and after the seminar. Methods The seminar consisted of lectures regarding intracavitary and interstitial brachytherapy in the morning and hands-on practice of needle insertion and contouring, as well as dose calculation practice using the radiation treatment system in the evening. Prior to and following the seminar, participants completed a questionnaire asking about their level of confidence in performing intracavitary and interstitial brachytherapy, expressed between 0 and 10 (the higher the number, the stronger the confidence). Results A total of 15 physicians, six medical physicists and eight radiation technologists from 11 institutions attended the meeting. The median level of confidence before and after the seminar was 3 (range, 0–6) and 5.5 (range, 3–7), respectively, and a statistically significant improvement was observed (P Conclusion It was suggested that the hands-on seminar on intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer improved the level of confidence of the attendees and propelled their motivation, through which it is expected that the implementation of intracavitary and interstitial brachytherapy will be accelerated.

Purpose We investigated the immobilization accuracy of a new type of thermoplastic mask—the Double Shell Positioning System (DSPS)—in terms of geometry and dose delivery. Methods Thirty‐one consecutive patients with 1–5 brain metastases treated with stereotactic radiotherapy (SRT) were selected and divided into two groups. Patients were divided into two groups. One group of patients was immobilized by the DSPS (n = 9). Another group of patients was immobilized by a combination of the DSPS and a mouthpiece (n = 22). Patient repositioning was performed with cone beam computed tomography (CBCT) and six‐degree of freedom couch. Additionally, CBCT images were acquired before and after treatment. Registration errors were analyzed with off‐line review. The inter‐ and intrafractional setup errors, and planning target volume (PTV) margin were also calculated. Delivered doses were calculated by shifting the isocenter according to inter‐ and intrafractional setup errors. Dose differences of GTV D99% were compared between planned and delivered doses against the modified PTV margin of 1 mm. Results Interfractional setup errors associated with the mouthpiece group were significantly smaller than the translation errors in another group (p = 0.03). Intrafractional setup errors for the two groups were almost the same in all directions. PTV margins were 0.89 mm, 0.75 mm, and 0.90 mm for the DSPS combined with the mouthpiece in lateral, vertical, and longitudinal directions, respectively. Similarly, PTV margins were 1.20 mm, 0.72 mm, and 1.37 mm for the DSPS in the lateral, vertical, and longitudinal directions, respectively. Dose differences between planned and delivered doses were small enough to be within 1% for both groups. Conclusions The geometric and dosimetric assessments revealed that the DSPS provides sufficient immobilization accuracy. Higher accuracy can be expected when the immobilization is combined with the use of a mouthpiece.

Lymphopenia at diagnosis is considered a negative prognostic factor for patients with extra-nodal natural killer (NK)/T-cell lymphoma (ENKTL), especially that of the absolute cluster of differentiation 4We analyzed the clinical data of 176 patients who met the inclusion criteria in Cancer Center of Integrated Hospital of Traditional Chinese Medicine, Southern Medical University from 2000 to 2018, including baseline clinical factors and ACD4C detected by flow cytometry, and examined the correlation between the results and clinical parameters and long-term outcomes.The complete response rate of the high ACD4C group was 57.6%, which was significantly higher than that of the low ACD4C group (15.1%, P0.001). The univariate analysis results showed that at a median follow-up time of 58.2 months, patients with a high ACD4C had significantly superior progression-free survival (PFS) and overall survival (OS) (P=0.034 and P=0.001, respectively). The multivariate analysis results revealed that Eastern Cooperative Oncology Group performance status (ECOG PS) and the ACD4C were independent prognostic factors for OS [RR (95% CI): 2.288 (1.209-4.328), P=0.011 and RR (95% CI): 2.058 (1.070-3.968), P=0.031, respectively]. ECOG PS was also an independent prognostic factor for PFS [RR (95% CI): 1.858 (1.064-3.244), P=0.029], while ACD4C tended to be independently correlated with PFS (P=0.085).In this large cohort study, we found that the ACD4C was associated with survival outcomes in ENKTL patients. It is a potential biomarker, which may potentially be applied to clinical.

Background International guidelines recommend brachytherapy for patients with dysphagia from esophageal cancer, whereas brachytherapy is infrequently used to palliate dysphagia in some countries. To clarify the availability of palliative treatment for dysphagia from esophageal cancer and explain why brachytherapy is not routinely performed are unknown, this study investigated the use of brachytherapy and external beam radiotherapy for dysphagia from esophageal cancer. Methods Japanese Radiation Oncology Study Group members completed a survey and selected the treatment that they would recommend for hypothetical cases of dysphagia from esophageal cancer. Results Of the 136 invited facilities, 61 completed the survey (44.9%). Four (6.6%) facilities performed brachytherapy of the esophagus, whereas brachytherapy represented the first-line treatment at three (4.9%) facilities. Conversely, external beam radiotherapy alone and chemoradiotherapy were first-line treatments at 61 and 58 (95.1%) facilities, respectively. In facilities that performed brachytherapy, the main reason why brachytherapy of the esophagus was not performed was high invasiveness (30.2%). Definitive-dose chemoradiotherapy with (≥50 Gy) tended to be used in patients with expected long-term survival. Conclusions Few facilities routinely considered brachytherapy for the treatment of dysphagia from esophageal cancer in Japan. Conversely, most facilities routinely considered external beam radiotherapy. In the future, it will be necessary to optimize external beam radiotherapy.

Evidence regarding postoperative radiation therapy (PORT) for metastases to the long bones is lacking. Characterizing the current practice patterns and identifying factors that influence dose-fractionation schedules are essential for future clinical trials. An internet-based survey of the palliative RT subgroup of the Japanese Radiation Oncology Study Group was performed in 2017 to collect data regarding PORT prescription practices and dose-fractionation schedules. Responders were also asked to recommend dose-fractionation schedules for four hypothetical cases that involved a patient with impending pathological fractures and one of four clinical features (poor prognosis, solitary metastasis, radio-resistant primary tumor or expected long-term survival). Responders were asked to indicate their preferred irradiation fields and the reasons for the dose fractionation schedule they chose. Responses were obtained from 89 radiation oncologists (67 institutions and 151 RT plans) who used 22 dose-fractionation schedules, with the most commonly used and recommended schedule being 30 Gy in 10 fractions. Local control was the most common reason for preferring longer-course RT. High-dose fractionated schedules were preferred for oligometastasis, and low-dose regimens were preferred for patients with a poor prognosis; however, single-fraction RT was not preferred. Most respondents recommended targeting the entire orthopedic prosthesis. These results indicated that PORT using 30 Gy in 10 fractions to the entire orthopedic prosthesis is preferred in current Japanese practice and that single-fraction RT was not preferred. Oligometastasis and poor prognosis influenced the selection of high- or low-dose regimens.

Background The aim of this study was to evaluate the long-term treatment results of combined superselective intraarterial chemotherapy and radiation therapy for advanced maxillary sinus cancer (MSC) and the incidence of regional lymph node failure, and to reveal the clinical and anatomical predictive factors for metastasis. Methods We retrospectively evaluated 55 consecutive patients with locally advanced squamous cell carcinoma of the maxillary sinus who were treated with external radiotherapy and superselective intraarterial chemotherapy. Elective nodal irradiation (ENI) was performed only in the clinical node-positive (cN+) cases and not in the clinical node-negative (cN0) cases. Results: Thirty-eight patients were cN0, and 17 were cN+ at diagnosis. Regional lymph node metastases occurred in 7 of 38 patients with cN0, and 2 of 17 with cN+ during the median follow-up period of 36 months. There were more cases of high-grade (3 or 4) late adverse events in the ENI group than in the non-ENI group (13% vs. 41%, respectively; p = 0.03). In cN0 cases without ENI, invasion of the pterygoid plates (57% vs. 90%; p p = 0.02) was significantly correlated with a low 5-year regional recurrence-free rate. Conclusions Patients with MCS and invasion of the pterygoid plates and oral cavity can be considered appropriate candidates for ENI.

We conducted a prospective study to quantitatively evaluate the movement of the chest wall to establish the simple and reproducible deep-inspiration breath-hold (DIBH) method. The left nipple position was monitored to confirm the inspiratory state. Planning computed tomography (CT) was performed under DIBH and free-breath. We conducted radiation plans with DIBH and free-breath CT and evaluated organ at risk (OAR) and target doses according to two different plans. The relationship between positioning errors of the chest wall and patient factors was evaluated using univariate analysis and fixed-effects models. Twenty-three patients aged ≤ 60 years were enrolled during January–August 2021; 358 daily radiation treatments were evaluated. The median time of treatment room occupancy was 16 minutes (interquartile range, 14–20). The area of the planning target volume (PTV) surrounded by the 95% isodose line was more extensive in DIBH than in free breathing (71.6% vs 69.5%, P

Diffuse large B-cell lymphoma (DLBCL) is the most frequently occurring subtype of lymphoma. Unfortunately, the fundamental processes underlying the pathogenesis of DLBCL remain little understood. NThe mRNA and protein expression of Wilms tumor 1-associating protein (WTAP) were determined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis in lymphoma cells lines. The effects of WTAP expression on human lymphoma cells lines were assessed using cell proliferation assays, colony formation assays, and CCK8 assays. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to screen candidate gene targets of WTAP. Finally, the regulatory mechanisms of WTAP in DLBCL were investigated using methylated RNA immunoprecipitation (MeRIP) assays.This study investigated the precise function of WTAP in DLBCL formation. The results demonstrated that the levels of mIn conclusion, these findings demonstrated that WTAP promotes DLBCL development via modulation of m

Purpose Improving pain interference in daily activities, rather than mere pain reduction, is a desirable endpoint for palliative radiation therapy. The association between pain response and pain interference has been studied almost exclusively in patients with painful bone metastases (PBMs), whereas nonindex pain has scarcely been explored in palliative radiation therapy. We investigated whether index and nonindex pain endpoints are associated with pain interference changes in patients with both PBMs and painful non-bone-metastasis tumors (PNTs). Methods and Materials Brief pain inventory data collected at baseline and at 2 months post-treatment were used to calculate differences in pain interference scores. Pain response in terms of the index pain was assessed using the international consensus endpoint. Patients were diagnosed with predominance of other pain (POP) if nonindex pain of malignant or unknown origin was present and had a greater pain score than the index pain. Results Of 302 patients, 127 (42%) had PBMs and 175 (58%) had PNTs. The median pain interference score, which is based on the mean of the 7 subscale items, decreased to a greater extent among responders than among nonresponders (PBM group: –3.43 vs –0.57 [P = .005]; PNT group: –2.43 vs –0.29 [P < .001]). Moreover, patients without POP experienced a greater reduction in their median pain interference score than did those with POP (PBM group: –2.71 vs +0.43 [P = .004]; PNT group: –2.00 vs +1.57 [P = .007]). The Jonckheere-Terpstra test showed a significant trend across 4 pain response categories in patients with PBMs and those with PNTs (P < .001 for both). Conclusions The index and nonindex pain endpoints were positively and negatively associated with improvement in pain interference, respectively. There was no apparent difference between patients with PBMs and PNTs in terms of the associations of these endpoints with pain interference.

Highlights • The frequency of use of the ICT has risen in research for PBMs. • The frequency of the ICT use has been considerably limited for PNTs. • None of the journal articles had investigated non-index pain., Background and purpose Consistent assessment of the pain response is essential for adequately comparing treatment efficacy between studies. We studied the assessment of pain endpoints in radiotherapy for painful bone metastases (PBMs) and painful non-bone-metastasis tumors (PNTs). Material and methods We performed a literature search in the Green (Radiotherapy and Oncology) and Red (International Journal of Radiation Oncology * Biology * Physics) Journals for full-length original articles published between 2009 and 2018. We only included articles that assessed palliation of tumor-related pain after radiotherapy. The data obtained included the definitions of pain response and assessment of non-index pain (pain other than that related to the irradiated tumors). Results Among the 1812 articles identified using the journals’ search function, 60 were included in the analysis. Thirty percent of the PBM articles and approximately half of the PNT articles did not report on analgesic use. Among the prospective studies, 68% of the articles on PBMs and 10% of the articles on PNTs used the International Consensus Endpoint. The PBM articles published in 2014–2018 utilized the International Consensus Endpoint more frequently than those published in 2009–2013 (p = 0.049). No articles reported information on non-index pain. Conclusions After the initial publication of the International Consensus Endpoint, the frequency of its use appears to have risen in PBM research; however, its use in PNT studies has been considerably limited. The International Consensus Endpoint should be consistently utilized in future studies on radiotherapy for painful tumors. Since none of the journal articles had investigated non-index pain, this issue may also needs to be addressed.

We aimed to compare the safety of radiotherapy with concurrent docetaxel (DOC-RT) for esophageal cancer (EC) in elderly patients who were divided into a creatinine clearance (Ccr)

Purpose: A quality indicator (QI) is a valuable tool to evaluate the quality of health care systems. In palliative radiation oncology, only a few of its related QIs have been developed to date. In this study, we sought to develop and pilot test QIs that assess the quality of care in palliative radiation therapy. Methods and materials: A modified Delphi method was used to establish consensus with an expert panel. The panel consisted of eight radiation oncologists who have expertise in palliative radiation oncology and one expert on Delphi methodology. Online panel meetings and e-mail surveys were conducted to develop QIs on palliative radiation therapy for bone and brain metastases. Feasibility of measurement was assessed though pilot surveys that were conducted by radiation oncologists at five facilities. Results: After three online meetings and two e-mail surveys, we developed four QIs on bone metastases and three QIs on brain metastases. Two email surveys and two pilot surveys confirmed the validity of QIs and the feasibility of measurement, respectively. Conclusions: We developed valid and feasible QIs on palliative radiation therapy for bone and brain metastases. Our work may contribute to reduce the evidence-practice gaps in palliative radiation oncology.

Palliative radiotherapy seems to be rarely performed for incurable gastric cancer. In this first multicenter study, we examined the effectiveness of palliative radiotherapy and investigated whether biologically effective dose (BED) is associated with survival, response, or re-bleeding. Eligibility criteria included blood transfusion or hemoglobin levels

Objective Stereotactic body radiotherapy has emerged as an attractive alternative to conventional radiotherapy for spinal metastases. However, it has limitations, including the need for advanced techniques and specific adverse effects. The present trial aimed to validate the feasibility and safety of stereotactic body radiotherapy in Japanese patients with spinal metastases. Methods Patients with one or two spinal metastases received stereotactic body radiotherapy of 24 Gy in two fractions. The primary endpoint was the proportion of severe adverse effects (≥ grade 3) in patients within 6 months after spine stereotactic body radiotherapy. Adverse effects were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4. The treatment protocol was considered feasible and tolerable if the proportion of severe adverse effects was 10% or less. Results Overall, 20 spinal segments in 20 patients who registered between March 2014 and October 2015 were included. Minor and major deviations were observed in the planning of 2 and 0 cases, respectively. The treatment completion rate was 100%. The median follow-up after registration was 24.5 (range: 1–61) months. Although four patients experienced acute grade 2 adverse effects, no grade 3 or higher adverse effects were observed within 6 months after spine stereotactic body radiotherapy. Vertebral compression fractures were observed in two patients (14 and 16 months after stereotactic body radiotherapy). The local control and pain response rates at 6 months were 100 and 83%, respectively. Conclusion This study demonstrated the feasibility and safety of spine stereotactic body radiotherapy in Japanese patients with spinal metastases.

We developed a new head supporting device to provide accurate correction of rotational setup during image‐guided radiation therapy (IGRT), evaluating its correction performance and the efficacy of dose distribution in stereotactic radiotherapy (SRT) using a helical tomotherapy (HT) system. The accuracy of rotational motion was measured using an electronic inclinometer; we compared device angles and measurement values from 0.0° to 3.0°. The correction accuracy was investigated based on the distance between rotational centers in the device and on megavoltage computed tomography (MVCT); the correction values were compared using distances in the range of 0.0–9.0 cm using a head phantom with a rotational error of 1.5°. For an SRT with a simultaneous integrated boost plan and a rotational error of 3.0° in yaw angle using a head phantom, and for a single‐isocenter SRT for multiple brain metastases in the data of three patients, dosimetric efficacy of the HT unit was evaluated for calculated dose distributions with MVCT after rotational correction. This device can correct pitch and yaw angles within 0.3° and can be corrected to within 0.5° for each rotational angle according to the result of MVCT correction regardless of the rotational center position. In the head phantom study, the device had a beneficial impact on rotational correction; D99% for the target improved by approximately 10% with rotational correction. Using patient data with the device, the mean difference based on the treatment planning data was 0.3% for D99% and −0.1% for coverage index to the target. Our rotational setup correction device has high efficacy, and can be used for IGRT.

Total body irradiation (TBI) using helical tomotherapy (HT) has advantages over the standard linear accelerator-based approach to the conditioning regimen for hematopoietic cell transplantation. However, the radiation field has to be divided into two independent irradiation plans to deliver a homogeneous dose to the whole body. A clinical target volume near the skin increases the skin surface dose; therefore, high- or low-dose regions arise depending on the set-up position accuracy because the two radiation fields are somewhat overlapped or separated. We aimed to determine an adequate treatment planning method robust to the set-up accuracy for the field joint dose distribution using HT-TBI. We calculated treatment plans reducing target volumes at the interface between the upper and lower body irradiations and evaluated these joint dose distributions via simulation and experimental studies. Target volumes used for the optimization calculation were reduced by 0, 0.5, 1.0, 2.0, 2.5, and 3.0 cm from the boundary surface on the upper and lower sides. Combined dose distributions with set-up error simulated by modifying coordinate positions were investigated to find the optimal planning method. In the ideal set-up position, the target volume without a gap area caused field junctional doses of up to approximately 200%; therefore, target volumes reduced by 2.0-3.0 cm could suppress the maximum dose to within 150%. However, with set-up error, high-dose areas exceeding 150% and low-dose areas below 100% were found with 2.0 and 3.0 cm target volume reduction. Using the dynamic jaw (DJ) system, dose deviations caused by set-up error reached approximately 20%, which is not suitable for HT-TBI. Moreover, these dose distributions can be easily adjusted when combined with the intensity modulation technique for field boundary regions. The results of a simulation and experimental study using a film dosimetry were almost identical, which indicated that reducing the target volume at the field boundary surface by 2.5 cm produces the most appropriate target definition.

Objective To determine the most appropriate radiologic criteria of metastatic retropharyngeal lymph nodes (RLNs) in patients with maxillary sinus cancer (MSC). Materials and methods We retrospectively evaluated 16 consecutive patients who underwent magnetic resonance imaging (MRI) before and after the treatment of locally advanced squamous cell carcinoma of the maxillary sinus. The minimal and maximal diameters of all RLNS were recorded. RLNs were classified as metastatic on the basis of the MRI follow-up (f/u). RLNs were considered non-metastatic if stable disease continued until the final MRI f/u and metastatic in cases with different evaluations (complete response, partial response, progressive disease) determined using Response Evaluation Criteria in Solid Tumours (RECIST) ver. 1.1. The receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to assess the accuracy of various criteria in the diagnosis of metastatic RLNs. Results Of the 34 RLNs in 16 cases observed on pretreatment MRI, 7 were classified as metastatic RLNs and 27 as non-metastatic RLNs. Using the radiologic criteria, metastatic RLNs tended to be diagnosed more accurately with the minimal axial diameter than with the maximal axial diameter (AUC; 0.97 vs. 0.73, p = 0.06). The most accurate size criterion of metastatic RLNs was a minimal axial diameter of 5 mm or larger, with an accuracy of 94.1% (32 of 34). Conclusions The most appropriate radiologic criterion of metastatic RLNs in MSC is a minimal axial diameter of 5 mm or longer.

PURPOSE/OBJECTIVE(S) In the largest prospective study to date, we examined the effectiveness of palliative radiation therapy for bleeding gastric cancer, and the association of the biologically effective dose (BED) with survival, bleeding response, or re-bleeding. MATERIALS/METHODS We recruited patients with incurable gastric cancer for whom palliative radiation therapy was planned. Eligibility criteria included blood transfusion or hemoglobin levels < 8.0 g/dL. The primary endpoint was the intention-to-treat (ITT) response rate at four weeks. Response entailed all of the following criteria: 1) hemoglobin levels ≥ 8.0 g/dL, 2) seven consecutive days from enrollment to blood sampling without blood transfusion, and 3) no salvage treatment (surgery, endoscopic treatment, transcatheter embolization, or reirradiation) for bleeding gastric cancer. Re-bleeding was defined as the need for blood transfusion or salvage treatment. Response was assessed at 2, 4, and 8 weeks after enrollment; re-bleeding was assessed monthly during the 6-month follow-up. Sample size was designed with the probability of obtaining a 90% confidence interval (CI) ≤ ± 15% being set at 0.8, assuming a per-protocol (PP) response rate of 70% at 4 weeks. RESULTS We enrolled 55 patients from 15 institutions. A median total radiation dose of 20 Gy (range, 8-45 Gy) was delivered in a median of five fractions. Of the 55 patients, 38 responded to treatment; of the 38 responders, 19 (50%) died and 12 (32%) experienced re-bleeding. The ITT response rates were 47%, 53% (95% CI, 39%-66%), and 49% at 2, 4, and 8 weeks, respectively. The PP response rates were 55%, 78%, and 90% at 2, 4, and 8 weeks, respectively. Restricted mean response and re-bleeding time up to 8 months were 2.3 months and 0.8 months, respectively. The median overall survival was 3.8 months (median follow-up, 12.1 months). The multivariable Cox model showed that neither response (a time-dependent covariate) (hazard ratio [HR], 1.04; 95% CI, 0.44-2.48) nor BED (alpha/beta = 10) (HR, 0.98; 95% CI, 0.95-1.02) were significant predictors of overall survival. The multivariable Fine-Gray model showed that BED was not a significant predictor of response (subdistribution HR, 1.02; 95% CI, 0.99-1.06). The univariable Cox model on transition hazard from response to re-bleeding showed that BED was not significantly associated with re-bleeding (HR, 0.98; 95% CI, 0.92-1.04). Grade 1, 2, 3, and ≥ 4 radiation-related adverse events were reported in 11, 9, 1, and 0 patients, respectively. CONCLUSION The PP bleeding response rate increased to 90% during the 8-week follow-up period. The frequent occurrence of death from shortly after enrollment lowered the ITT response rate and shortened the duration of response. BED was not significantly associated with survival, bleeding response, or re-bleeding.

OBJECTIVE This is an ancillary study of a multi-institutional randomized non-inferiority phase III trial of accelerated fractionation (AF) versus standard fractionation (SF) radiation therapy for T1-2N0M0 glottic cancer (JCOG0701). Biopsy specimens of tumors from the patients enrolled in the JCOG0701 are collected and the association between clinical outcomes and histopathologic features such as expression of epithelial cell adhesion molecule (EpCAM), p53, and p16 were investigated. METHODS Five slices of undyed slides from biopsy specimens were sent to the National Cancer Center Hospital and all the specimens were assessed for the expression of EpCAM, p53, and p16. The primary objective was to investigate the association between 3-year progression-free survival (PFS) and expression of EpCAM, p53, and p16. RESULTS A total of 88 out of 370 patients were enrolled in this ancillary study. The 3-year PFS for tumors with strong expression of EpCAM was 70.6% (95% CI 43.1%-86.6%), while that of tumors without strong expression of EpCAM was 77.5% (95% CI 65.9%-85.5%) with no remarkable difference between groups (P = .67). Likewise, there was no significant difference in 3-year PFS between tumors regardless of p53 or p16 status. However, in a subgroup analysis for 17 patients with a strong expression of EpCAM, AF showed better 3-year PFS than SF (100% vs 54.5%, P = .07). CONCLUSIONS From the current study, it could not be concluded that EpCAM, p16, and p53 were prognostic factors for early-stage glottic cancer after primary radiation therapy. AF might be an appropriate fractionation for tumors with a strong expression of EpCAM. LEVEL OF EVIDENCE 3 Laryngoscope, 131:1522-1527, 2021.

Background: The aim of this study was to evaluate the long-term treatment results of combined superselective intraarterial chemotherapy and radiation therapy for advanced maxillary sinus cancer (MSC) and the incidence of regional lymph node failure, and to reveal the clinical and anatomical predictive factors for metastasis.Methods: We retrospectively evaluated 55 consecutive patients with locally advanced squamous cell carcinoma of the maxillary sinus who were treated with external radiotherapy and superselective intraarterial chemotherapy. Elective nodal irradiation (ENI) was performed only in the clinical node-positive (cN+) cases and not in the clinical node-negative (cN0) cases.Results: Thirty-eight patients were cN0, and 17 were cN+ at diagnosis. Regional lymph node metastases occurred in 7 of 38 patients with cN0, and 2 of 17 with cN+ during the median follow-up period of 36 months. There were more cases of high-grade (3 or 4) late adverse events in the ENI group than in the non-ENI group (13% vs. 41%, respectively; p = 0.03). In cN0 cases without ENI, invasion of the pterygoid plates (57% vs. 90%; p < 0.01) and oral cavity (35% vs. 92%, with invasion vs without invasion, respectively; p = 0.02) was significantly correlated with a low 5-year regional recurrence-free rate.Conclusions: Patients with MCS and invasion of the pterygoid plates and oral cavity can be considered appropriate candidates for ENI.

BackgroundBecause of the lack of evidence on practice patterns of postoperative radiation therapy (PORT)in patients with metastases to the long bones, it is essential to characterize the current practice patterns and identify factors affecting dose-fractionation to aid future clinical trials. MethodsThe palliative radiation therapy subgroup of the Japanese Radiation Oncology Study Group conducted an internet-based survey to determine the prescription practices and various dose-fractionations used for PORT. Additionally, responders were asked to recommend dose-fractionations in four hypothetical cancer cases, wherein each case represented a patient with impending pathological fractures and one of the four features: limited prognosis, solitary metastasis, radio-resistant primary tumor, or long-term survival. Responders were asked to indicate their preferred irradiation fields and the reasons for choosing long-course radiotherapy over short-course radiotherapy (RT). ResultsEighty-nine radiation oncologists from 67 institutions and 151 RT plans were included. Twenty-two different dose-fractionations were used; the most commonly used and recommended dose-fractionation was 30 Gy in 10 fractions. “Local control” was most the common reason for preferring longer course RT. While fractionated higher-dose regimens were preferred in case of oligometastasis, low dose regimens were preferred in case of limited prognosis; single fraction RT was never preferred. Most respondents recommended involvement of “the entire orthopedic prosthesis.” ConclusionFor PORT of metastases to the long bones, 30 Gy in 10 fractions for the entire orthopedic prosthesis is preferred in current practice. Oligometastasis and a limited prognosis influence the selection of high- and low-dose regimens, respectively. Single fraction RT is never preferred.

There remains wide variation in the use of chest wall boluses for postmastectomy radiotherapy, which may result from the need for 2 treatment plans with the commonly used half-time tissue-equivalent 5-mm-thick bolus to achieve a full surface dose. To establish a bolus method requiring one treatment plan, we assessed the surface dose of a thinner daily bolus for all treatment fractions and compared it against the half-time 5-mm-thick bolus. In this basic study, we specifically investigated dosage achieved when using the following: (1) the existing bolus protocol, a half-time 5-mm-thick tissue-equivalent Clearfit bolus (Fujidenolo Inc., Aichi, JP); (2) no bolus; and (3) daily 1-, 2-, and 3-mm-thick Clearfit boluses at 4 and 6 MV photons. Dosimetric measurements were then taken in an anthropomorphic phantom to study the effect of each regimen on the surface doses, and the mean surface doses of the daily thinner boluses were compared with the existing bolus protocol by the Welch 2-sample t test. The mean surface doses for the existing bolus protocol, no bolus, and daily 1-, 2-, and 3-mm-thick boluses were 68% (range, 59% to 77%), 53% (41% to 66%), 73% (60% to 83%), 77% (66% to 87%), and 82% (75% to 91%) of the prescription dose at 4 MV, respectively; the corresponding values at 6 MV were 71% (63% to 79%), 50% (39% to 60%), 72% (56% to 83%), 81% (68% to 90%), and 89% (80 to 97%) of the prescription dose. The mean surface doses were comparable between the existing bolus protocol and the 1-mm-thick daily bolus at 4 and 6 MV. In conclusion, the mean surface dose of a 1-mm-thick bolus approximate that of a half-time 5-mm-thick bolus at 4 and 6 MV. As such, we have started a prospective clinical study on the safety and efficacy of a 1-mm-thick bolus for postmastectomy radiotherapy.

Purpose Palliative radiotherapy is the standard of care for bone metastases. However, skeletal-related events, defined as a pathologic fracture, paraplegia, surgery or radiotherapy for local recurrence, or severe pain in previously irradiated bone with radio-resistant histology type still present high incidence. The primary objective of this study was to determine whether zoledronic acid hydrate and palliative radiotherapy could prevent local skeletal-related events. Methods Eligible patients with bone metastases from renal cell carcinoma were treated with zoledronic acid hydrate every 3 or 4 weeks and concurrent palliative radiotherapy of 30 Gy in 3 Gy fractions. The criteria for radiotherapy were established by the treating physician, but patients with complicated bone metastases (impending pathological fracture or spinal cord compression) which needed immediate surgery were excluded. The primary endpoint was the local skeletal-related event-free survival rate at 1 year. Results Twenty-seven patients were included in the study. The median age was 65 (range, 50–84) years. Radiotherapy dose was 30 Gy for all patients except 1 whose radiotherapy was terminated due to brain metastasis progression at 18 Gy. Zoledronic acid hydrate was administered in a median of 12 (range, 0–34) times. The median follow-up period was 12 months and 19 months in patients who were still alive. Of 27 patients in the efficacy analysis, the 1-year local skeletal-related event-free rate was 77.6% (80% confidence interval, 66.2–89.0). Common grade 3 toxicities were hypocalcemia (1 [4%]), sGPT level increase (1 [4%]) and sGOT level increase (1 [4%]). There was no grade 4 or 5 toxicity. Conclusion Zoledronic acid hydrate administration and palliative radiotherapy were a well-tolerated and promising treatment reducing skeletal-related events for bone metastases from renal cell carcinoma.

Long-term follow-up of Japanese women with breast cancer who underwent hypofractionated whole-breast irradiation (HF-WBI) has not been well documented. Therefore, we compared the treatment results of HF-WBI and conventional fractionated (CF)-WBI. Patients with stage 0–II breast cancer receiving partial mastectomy were eligible for this prospective observational study. The HF-WBI consisted of 43.2 Gy in 16 fractions to the whole breast, with an additional tumor-bed boost of 8.1 Gy in three fractions for patients with positive or less than 5 mm surgical margins. A total of 615 patients (400: HF-WBI and 215: CF-WBI) who were treated between 2006 and 2008 were investigated. Propensity score matching was conducted based on age, tumor grade, and margin status, and 372 matched cases were investigated for examining factors relating to intrabreast tumor recurrence (IBTR). With a median follow-up period of 9.4 years, age and margin status were independent factors associated with IBTR occurrence (P = 0.006 and 0.016, respectively). The 10-year ipsilateral breast tumor control (IBTC) rates after HF-WBI and CF-WBI were 96.5% and 95.3%, respectively (P = 0.606). The 10-year IBTC rates according to margin status were 88.0% with positive margins, 94.9% with 5 mm margins, and 98.0% with negative margins (P = 0.014). There was no difference in IBTC between CF-WBI and HF-WBI in our patients. Positive surgical margin was a risk factor independently associated with IBTC rates after CF-WBI and HF-WBI. Further investigation is required to establish adequate treatment strategies for patients with positive surgical margins.

Background We assessed the non-inferiority of accelerated fractionation (AF) (2.4 Gy/fraction) compared with standard fractionation (SF) (2 Gy/fraction) regarding progression-free survival (PFS) in patients with T1-2N0M0 glottic cancer (GC). Patients and methods In this multi-institutional, randomized, phase III trial, patients were enrolled from 32 Japanese institutions. Key inclusion criteria were GC T1-2N0M0, age 20–80, Eastern Cooperative Oncology Group performance status of 0–1, and adequate organ function. Patients were randomly assigned to receive either SF of 66–70 Gy (33–35 fractions), or AF of 60–64.8 Gy (25–27 fractions). The primary end point was the proportion of 3-year PFS. The planned sample size was 360 with a non-inferiority margin of 5%. Results Between 2007 and 2013, 370 patients were randomized (184/186 to SF/AF). Three-year PFS was 79.9%(95% confidence interval [CI] 73.4–85.4) for SF and 81.7% (95% CI 75.4–87.0) for AF (difference 1.8%, 91% CI−5.1% to 8.8%; one-sided P = 0.047 > 0.045). The cumulative incidences of local failure at 3 years for SF/AF were 15.9%/10.3%. No significant difference was observed in 3-year overall survival (OS) between SF and AF. Grade 3 or 4 acute and late toxicities developed in 22 (12.4%)/21 (11.5%) and 2 (1.1%)/1 (0.5%) in the SF/AF arms. Conclusion Although the non-inferiority of AF was not confirmed statistically, the similar efficacy and toxicity of AF compared with SF, as well as the practical convenience of its fewer treatment sessions, suggest the potential of AF as a treatment option for early GC. Clinical trials registration UMIN Clinical Trial Registry, number UMIN000000819.

PURPOSE/OBJECTIVE(S) While the non-inferiority of hypofractionation (HF) to conventional fractionation for prostate cancer had been investigated in some randomized clinical trials, we started a multi-institutional phase II study to confirm the safety with the efficacy of HF intensity-modulated radiotherapy (IMRT) with image-guided technique for Japanese patients. MATERIALS/METHODS Eligibility criteria of the study included: pathologically proven adenocarcinoma; low or intermediate risk (cT1-T2c, PSA ≤ 20 and Gleason score (GS) ≤ 7) or high risk having one of the following factors, cT3a, PSA > 20/ ≤ 30, or GS = 8/9; cN0M0; age 50-80; performance status (PS) 0-1; written informed consent. HF IMRT with 70 Gy/28 fr (2.5 Gy/fr) was performed. The position of the prostate gland or inserted fiducial markers was verified with a full bladder before each treatment. Neoadjuvant hormonal therapy (HT) for 4-8 months was allowed for patients with intermediate or high risk. The GTV was defined as the prostate (+ extracapsular invasion for cT3a). The CTV was defined as the GTV for low risk, and the GTV plus proximal seminal vesicles for intermediate and high risk. The PTV was defined as the CTV plus 4-8 mm margins for organ motions and set-up errors. The bladder, rectum, small and large intestines, and femoral heads were defined as the organs at risk (OAR) as the solid organ. The dose prescription was D50% for the PTV, with Dmax ≤ 105% and Dmin ≥ 95%. The dose constraints for OARs were defined as follows: bladder V70/V65/V60/V55, 15%/25%/35%/50%; rectum V65/V55/V50/V45, 15%/25%/35%/50%; small intestine V55 < 0.5 cc; large intestine V60 < 0.5 cc; femoral heads Vmax ≤ 50 Gy. The primary endpoint was the incidence of late toxicities at 5 years. The secondary endpoints were the incidence of acute toxicities, biochemical failure-free, clinical failure-free, and overall survivals at 5 years. The sample size was calculated to 130 patients using alpha/beta errors of 0.05/0.2, with the threshold/expectation values of ≥ grade 2 late toxicities as 15%/7%. RESULTS From Jul/2012 to Oct/2014, 134 patients from 20 institutions were registered. Patients and tumor characteristics were as follows: median age 71 (54 - 79); cT1c/T2a/T2b/T2c/T3a, 53/50/7/19/5; GS 6/7/8/9, 32/80/16/6; median pretreatment PSA 9.0 ng/ml (3.15 - 28.6); low/intermediate/high risk, 20 (15%)/80 (60%)/34 (25%); PS 0/1, 67/67. HT was used for 121 patients (90%). The median follow-up time was 5.16 years. The incidences of grade 2/ ≥ 3 gastrointestinal and genitourinary late toxicities at 5 years (primary endpoint) were 5.3%/0% and 5.3%/0%, respectively. The corresponding figures of acute toxicities were 3.8%/0% and 14.5%/0%, respectively. The biochemical failure-free, clinical failure-free, and overall survivals at 5 years were 90.4%, 93.8%, and 94.5%, respectively. CONCLUSION The primary endpoint was met, and the safety and efficacy of HF IMRT was confirmed in this trial, and accepted as one of the standard of care for Japanese patients with prostate cancer.

Purpose/Objective(s) To achieve high-precision stereotactic body radiotherapy, visualization of moving tumor/target estimation is performed using 4-dimensional cone-beam computed tomography (4D-CBCT) before each treatment fraction. Currently, respiration-correlated 4D-CBCT is achieved with subgroups of cone-beam projections into different respiratory phases. However, insufficient projections inside each phase bin cause severe imaging artifacts. Convolutional neural networks are widely used to correct CBCT specific artifacts. Previous research has shown that mean absolute error in Hounsfield units improved up to 93% over the original CBCT image. However, slight voxel-wise misalignment between the training images may lead to blurred synthesis, and hence, due to respiratory motion, it is impossible to perform 4D-CBCT imaging without organ misalignment with the 4D-computed tomography (4D-CT). Cycle-generative adversarial network (cycle-GAN) framework enforces an inverse transformation and achieves high accurate consistency even in mapping nonlinear domains. The aim of this study was to improve 4D-CBCT image quality using cycle-GAN and evaluate its use in adaptive radiation therapy (ART) planning for lung cancer. Materials/Methods Unpaired 4D-CT and 4D-CBCT taken from publicly available datasets in 5 patients who underwent lung cancer treatment were used for training using cycle-GAN model. Then, Synthesis of 4D-CBCT (Syn-CBCT) images with improved quality conferred by the cycle-GAN model was tested in another 5 cases in the lung region. To assess pixel value deviation and image similarity, mean absolute errors (MAE) and structural similarity index measure (SSIM) were calculated for Syn-CBCT and paired 4D-CT images and compared with those of original 4D-CBCT images. Moreover, volumetric modulation arc therapy plans with a dose of 48 Gy in 4 fractions were recalculated based on Syn-CBCT images, and 3-dimensional (3D)-gamma (3%/3 mm) analysis was conducted to compare the former with ideal dose distributions observed in 4D-CT images. Results 4D-CBCT imaging quality was improved and lung tumor regions were clearly observed after noise and artifact removal by applying the trained cycle-GAN model. MAEs were improved by 21% and SSIMs by 46% for whole images. Hence, pixel value and structural visualization in Syn-CBCT images could achieve near-ideal quality of 4D-CT images. Large structures were generally consistent with those in paired 4D-CT images, whereas fine structures (pulmonary vessels and fine bones) were not completely duplicated. However, a mean 3D gamma pass rate of > 95% was achieved in all cases. Conclusion The proposed cycle-GAN method enhances 4D-CBCT image quality, making it comparable to that of 4D-CT images. Thus, clinical implementation of Syn-CBCT-based ART is feasible.

Using existing prognostic models, including the Graded Prognostic Assessment (GPA), it is difficult to identify patients with brain metastases (BMs) who are not likely to survive 2 months after whole-brain radiotherapy (WBRT). The purpose of this study was to identify a subgroup of patients who would not benefit clinically from WBRT. We retrospectively reviewed the records of 111 patients with BMs who were ineligible for surgery or stereotactic irradiation and who underwent WBRT between March 2013 and April 2016. Most patients were scheduled to receive a total dose of 30 Gy in 10 fractions. Non–small cell lung cancer represented the most common primary cancer type (67%), followed by breast cancer (12%). Median survival time (MST) was 109 days (range, 4–883). Univariate analysis identified five factors significantly associated with poor prognosis: performance status (PS) 2–4, perilesional edema, elevated serum lactate dehydrogenase (LDH), using steroids during WBRT, and presence of hepatic metastases. Multivariate analysis confirmed elevated LDH (>300 IU/l) as an independent predictor. MST for LDH >300 IU/l (n = 30) and LDH ≤300 IU/L (n = 87) cohorts were 47 days and 148 days, respectively (P < 0.001). MSTs for GPA 0–1 patients (n = 85) with and without elevated LDH were 37 days and 123 days, respectively (P < 0.001). More than half of the patients with GPA 0–1 and elevated LDH died within two months. Adding elevated LDH to the GPA will permit identification of patients with BMs who have extremely unfavorable prognoses.

Objectives Considering that therapeutic strategies for older adult patients with esophageal cancer (EC) remain controversial, we aimed to assess the safety of radiotherapy with concurrent docetaxel (DOC-RT) among older adult patients with EC. Materials and Methods Eligible patients included those aged ≥76 years who were diagnosed with esophageal squamous cell carcinoma. Patients received radiotherapy (60 Gy in 30 fractions) and concurrent docetaxel (10 mg/m2 weekly for six cycles). Survival, toxicity, and treatment completion rates were retrospectively evaluated. Results Among 84 older adult patients receiving radical radiotherapy or chemoradiotherapy, 73 receiving DOC-RT were studied. Median follow-up duration was 14 months (range, 2–101 months). The 1-, 3-, and 5-year overall survival rates were 63%, 33%, and 13%, respectively, with a median survival time of 21 months. Grade 3 acute toxicities included esophagitis (7%), esophageal fistula (3%), pneumonitis (1%), leukopenia (10%), and anemia (8%). Grade 3 late toxicities included esophageal stenosis (4%), pleural effusion (3%), pericardial effusion (1%), and pneumonitis (1%). Grade 4 and 5 toxicities were not observed. DOC-RT was discontinued due to deterioration in the general condition (6%), esophageal fistula (3%), pneumonia (1%), and pain (1%), resulting in a DOC-RT completion rate of 89% (65/73 patients). The non-completion group comprised a higher proportion of older adults (age ≥ 80 years) and undernourished [geriatric nutritional risk index (GNRI Conclusion DOC-RT can be a safe regimen for older adult patients with EC. Nonetheless, old age (≥80 years) and undernourishment (GNRI