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Purpose: This study aimed to investigate whether vitamin K 2 (menatetrenone) suppresses bone mineral density (BMD) loss in the irradiated region after radiotherapy (RT) in uterine cancer patients., Materials and Methods: Our study included 34 patients who underwent whole pelvic irradiation for uterine cancer between 2001 and 2010. The patients were categorized in two groups: (1) Vitamin K 2 (45 mg/day) administration group (group A) with 18 cases and (2) non-administered group (group B) with 16 cases. The duration of vitamin K 2 administration was 1 year or longer. BMD was measured before and immediately, 3 months, 6 months, 1 year, 1 year or more after RT., Results: Regarding change rate in the BMD of L3-L4 which was outside the irradiated field, no significant changes were observed in BMD after radiation in either groups compared to BMD before radiotherapy. Regarding change rate in BMD of L5-S1 which was inside the irradiated field, BMD reduced significantly at 6 months after radiotherapy compared to BMD before the start of radiotherapy in Group B (P = 0.0234). However, no significant change was seen in group A. Grade 2 and 3 insufficiency fractures appeared in both groups, one in each. Regarding outside the irradiation field, one patient developed compression fracture in L2 in group B, none occurred in group A . CONCLUSION: We suggest that vitamin K 2 could suppress the decrease in BMD due to whole pelvic radiotherapy. Further studies are needed in the future to improve quality of life such as the prevention of insufficiency fractures., Competing Interests: Declarations. Conflict of interest: The authors state that there are no conflicts of interest. Ethical approval: This study has been approved by Institutional Review Board of Hiroshima University (Clinical Trial Registration number: E-1836). Patient identifiers were removed, and this study was conducted in accordance with the Declaration of Helsinki. Informed consent: Informed consent was obtained from all individual participants included in the study., (© 2025. The Author(s).)

Objective. While the biological effective dose (BED) has been used to estimate the damage to tumor cells in radiotherapy, BED does not consider intrafractional interruption (IFI) occurring during irradiation. We aim to develop a framework to evaluate the decrease in BED [ΔBED] and to create a plan compensating for the decrease by IFI. Approach. ΔBEDwas calculated using a model based on the microdosimetric kinetic model (MKM) for four brain tumor cases treated using a volumetric-modulated arc therapy. Four biologically compensated plans (BCPs) were created in the treatment planning system by a single-time optimization using a base plan consideringΔBEDcreated in in-house software and optimization objectives for the original clinically delivered plan to achieve a homogeneous BED distribution within the planning target volume (PTV). The BED-volume histogram was evaluated for non-compensated plan and BCP with different timepoint of interruption, a percentage of gantry rotation angle (GRA) before interruption in planned GRA,ηand duration of interruptionτ. Characteristics of the dose accumulation were analyzed for different collimator angle sets, Plan A (10°, 85°) and Plan B (45° and 315°), for the first case. Main Results. Hot spots in theΔBEDdistribution forη= 25%, 50%, and 75% were observed at superior-and-interior ends, central region, and peripheral region in PTV, respectively. These behaviors could be understood by characteristics of the MKM-based model producing maximumΔBEDat 50% of the dose accumulation.ΔBED50%ranged 4.5%-6.6%, 5.0%-7.3%, and 5.3%-7.7% forτ= 60, 90, and 120 min, respectively. Plan A showed fast dose accumulation at superior and inferior edges while slow on peripheries in the lateral dose profile. Plan B showed more homogeneous PD distributions than Plan A during irradiation. Significance. The developed framework successfully evaluated and compensated for the decreased BED distribution., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Background: In patients with early-stage breast cancer following breast surgery, ultra-hypofractionated (UHF) breast/chest wall radiation therapy (RT) has been shown to be non-inferior to a moderate-hypofractionated (MHF) regimen, with a minimal risk of breast induration, in the FAST-Forward trial, and UHF is now becoming the standard regimen in Europe. Herein, we aimed to investigate Japanese patients' attitudes toward the UHF regimen., Methods: A questionnaire-based survey was conducted at 13 RT centers in nine prefectures across Japan. All patients underwent breast-conserving surgery, followed by either conventional fractionation (2 Gy/fr) or MHF (2.66 Gy/fr) whole-breast irradiation (WBI) with or without a tumor bed boost. The questionnaire consisted of 13 questions mainly addressing quality-of-life during RT. Key questions included an 11-point scale (0-10) for rating the patients' enthusiasm for the UHF regimen and prioritization of the following treatment-related effects: treatment efficacy, acute/late adverse effects, physical/emotional/financial burden, and breast cosmesis. The patient and treatment characteristics were assessed by a physician., Results: In total, 247 questionnaires were administered between November 2022 and June 2023. The age distribution was as follows: < 50:50 s:60 s: ≥ 70 = 59 (24%):76 (30%):63 (26%):49 (20%). Sixty-nine percent of patients rated their enthusiasm for the UHF regimen at ≥ 6 out of 10 points (45% rated 10/10). Treatment efficacy was the highest priority for most patients (89%), whereas breast cosmesis the lowest priority (53%)., Conclusions: Patients' enthusiasm for UHF-WBI was observed across the cohort. These results could motivate researchers and clinicians to introduce UHF regimens in clinical practice., (© 2024. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Bone metastases are often associated with pain and can occur in various types of cancer, significantly affecting patients' quality of life. Despite the high response rates to initial conventional radiotherapy in patients with painful spinal metastases, recurrence and inadequate response still occur. Thus, the development of a highly effective strategy for pain recurrence is crucial to improving the quality of life in patients with advanced metastatic cancer. This randomized phase III trial aims to confirm the superiority of re-irradiation with stereotactic body radiotherapy (24 Gy in 2 fractions) over conventional radiotherapy (8 Gy in a single fraction) in achieving a complete pain response at 12 weeks in patients with previously irradiated painful spinal metastases. A total of 158 patients from 33 hospitals will be enrolled in Japan over 3.5 years. This trial has been registered in the Japan Registry of Clinical Trials as jRCTs1030240172 (https://jrct.niph.go.jp/latest-detail/jRCT1030240172)., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Tumor blood vessels are highly leaky in structure and have poor blood perfusion, which hampers infiltration and function of CD8T cells within tumor. Normalizing tumor vessels is thus thought to be important in promoting the flux of immune T cells and enhancing ant-tumor immunity. However, how tumor vasculature is normalized is poorly understood. Metformin (Met) combined with ant-PD-1 therapy is known to stimulate proliferation of and to produce large amounts of IFNγ from tumor-infiltrating CD8T lymphocytes (CD8TILs). We found that the combination therapy promotes the pericyte coverage of tumor vascular endothelial cells (ECs) to improve blood perfusion and that it suppresses the hyperpermeability through the increase of VE-cadherin. Peripheral node addressin(PNAd) and vascular cell adhesion molecule (VCAM)-1, both implicated to promote tumor infiltration of CD8T cells, were also increased. Importantly, tumor vessel normalization, characterized as the reduced 70-kDa dextran leakage and the enhancement of VE-cadherin and VCAM-1, were canceled by anti-CD8 Ab or anti-IFNγ Ab injection to mice. The increased CD8TILs were also abrogated by anti-IFNγ Ab injection. In vascular ECs, flow cytometry analysis revealed that pSTAT1 expression was found to be associated with VE-cadherin expression. Moreover, in vitro treatment with Met and IFNγ enhanced VE-cadherin and VCAM-1 on human umbilical vein endothelial cells (HUVECs). The Kaplan-Meier method revealed a correlation of VE-cadherin or VCAM-1 levels with overall survival in patients treated with immune checkpoint inhibitors. These data indicate that IFNγ-mediated cross talk of CD8TILs with tumor vessels is important for creating a better tumor microenvironment and maintaining sustained antitumor immunity., Competing Interests: Competing interests statement:The authors declare no competing interest.

We sought to identify potential evidence-practice gaps in palliative radiotherapy using quality indicators (QIs), previously developed using a modified Delphi method. Seven QIs were used to assess the quality of radiotherapy for bone metastases (BoM) and brain metastases (BrM). Compliance rate was calculated as the percentage of patients for whom recommended medical care was conducted. Random effects models were used to estimate the pooled compliance rates. Of the 39 invited radiation oncologists, 29 (74%) from 29 centers participated in the survey; 13 (45%) were academic and 16 (55%) were non-academic hospitals. For the QIs, except for BoM-4, the pooled compliance rates were higher than 80%; however, for at least some of the centers, the compliance rate was lower than these pooled rates. For BoM-4 regarding steroid use concurrent with radiotherapy for malignant spinal cord compression, the pooled compliance rate was as low as 32%. For BoM-1 regarding the choice of radiation schedule, the compliance rate was higher in academic hospitals than in non-academic hospitals (P = 0.021). For BrM-3 regarding the initiation of radiotherapy without delay, the compliance rate was lower in academic hospitals than in non-academic hospitals (P = 0.016). In conclusion, overall, compliance rates were high; however, for many QIs, practice remains to be improved in at least some centers. Steroids are infrequently used concurrently with radiotherapy for malignant spinal cord compression., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

The effectiveness of single-fraction 8-Gy radiotherapy for painful bone metastases has been verified in numerous randomized controlled trials. However, few reports have described the effectiveness of single-fraction 8-Gy radiotherapy in painful tumors other than bone metastases. We conducted a retrospective analysis to evaluate the pain response to single-fraction 8-Gy radiotherapy in painful non-bone-metastasis tumors. We included patients who had received single-fraction 8-Gy radiotherapy for such tumors between January 2017 and December 2022, excluding those with brain metastases, hematological tumors and those who received re-irradiation. Pain response assessment was based on the best responses documented in the medical records and conducted by two radiation oncologists. A total of 36 eligible patients were included in this study. The irradiation sites included primary lesions in eight patients, lymph node metastases in eight, muscle metastases in seven, pleural dissemination in four, skin/subcutaneous metastases in four and other sites in five. Pain response was assessed in 24 patients after radiotherapy. Pain response rate was 88% in evaluable patients; 21 of the 24 patients experienced response. The median assessment date for pain response was 37 days (range: 8-156 days) after radiotherapy. Re-irradiation was performed in four patients (11%). Single-fraction 8-Gy radiotherapy seemed to be a promising treatment option for painful non-bone-metastasis tumors and warrants further investigation., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Objectives: Low-dose-rate brachytherapy (LDR-BT) with 198 Au grains and 192 Ir pins is an essential treatment option for oral cancer due to its high rate of local control and low invasiveness. However, the radiation exposure of medical radiation workers is concerning. Thus, we aimed to determine the radiation dose delivered to medical radiation workers during LDR-BT using 198 Au grains and 192 Ir pins for oral cancer., Methods: Thirty-two patients with oral cancer underwent 198 Au grain interstitial LDR-BT between June 2016 and May 2023, and 23 patients with tongue cancer underwent 192 Ir pin interstitial LDR-BT between March 2015 and November 2017 at our hospital. Dosimetry was performed by attaching a dosimeter to the chest pocket of the operator and assistant during 198 Au grain or 192 Ir pin LDR-BT. Since the operator also loads 198 Au grains into the implantation device, the operator's radiation dose includes the dose received during this preparation., Results: Mean radiation doses of the operators with 198 Au grain and 192 Ir pin LDR-BT were 165.8 and 211.2 μSv, respectively. Statistically significant differences between the radioactive sources of 198 Au grain and 192 Ir pin LDR-BT were observed (p = 0.0459). The mean radiation doses of the assistants with 198 Au grain and 192 Ir pin LDR-BT were 92.0 and 162.0 μSv, respectively. Statistically significant differences were observed between the radioactive sources of 198 Au grains and 192 Ir pin LDR-BT (p = 0.0003)., Conclusions: Regarding radioactive source differences, 192 Ir pin LDR-BT resulted in higher doses delivered to medical radiation workers than 198 Au grain LDR-BT., (© 2023. The Author(s) under exclusive licence to Japanese Society for Oral and Maxillofacial Radiology.)

Background and Purpose: The diaphragm respiratory motion (RM) could impact the target dose robustness in the lower esophageal cancer (EC). We aimed to develop a framework evaluating the impact of different RM patterns quantitatively in one patient, by creating virtual four-dimensional computed-tomography (v4DCT) images, which could lead to tailored treatment for the breathing pattern. We validated virtual 4D radiotherapy (v4DRT) along with exploring the acceptability of free-breathing volumetric modulated arc therapy (FB-VMAT)., Methods and Materials: We assessed 10 patients with superficial EC through their real 4DCT (r4DCT) scans. v4DCT images were derived from the end-inhalation computed tomography (CT) image (reference CT) and the v4DRT dose was accumulated dose over all phases. r4DRT diaphragm shifts were applied with magnitudes derived from r4DCT scans; clinical target volume (CTV) dose of v4DRT was compared with that of r4DRT to validate v4DRT. CTV dosage modifications and planning organ at risk volume (PRV) margins of the spinal cord were examined with the diaphragm movement. The percentage dose differences (ΔDx) were determined between the v4DRT and the dose calculated on the reference CT image., Results: The CTV ΔDx between the r4DRT and v4DRT were within 1% in cases with RM ≦ 15 mm. The average ΔD 100% and ΔD mean of the CTV ranging from 5 to 15 mm of diaphragm motion was 0.3% to 1.7% and 0.1% to 0.4%, respectively. All CTV index changes were within 3% and ΔD 1cc and ΔD 2cc of Cord PRV were within 1%., Conclusion: We postulate a novel method for evaluating the CTV robustness, comparable to the conventional r4DCT method under the diaphragm RM ≦ 15 mm permitting an impact of within 3% in FB-VMAT for EC on the CTV dose distribution., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Self-care demonstrated efficacy in preventing severe acute radiation dermatitis among patients with head and neck squamous cell carcinoma undergoing chemoradiotherapy (CRT). This prospective trial aimed to confirm the feasibility and safety of transcutaneous electrical sensory stimulation while examining the relationship between changes in self-care behavior through supportive care interventions and the severity of acute radiation dermatitis during CRT. Patients underwent assessments for dermatitis grading (Grades 1 to ≥3) and were interviewed regarding self-care practices. The self-care questionnaires comprised six items, and a point was deducted for each task that the patient could not perform independently. Statistical analysis was performed to determine the association between G3 radiation dermatitis and the lowest self-care behavior scores. Of the 10 patients enrolled, three experienced G3 dermatitis. During CRT, six patients maintained their initial scores and did not develop ≥G3 dermatitis. Meanwhile, three of four patients with decreased scores exhibited ≥G3 dermatitis. The group with ≥G3 dermatitis had significantly lower scores than those with ≤G2 dermatitis, suggesting that the inability of patients to perform self-care routinely may lead to severe acute radiation dermatitis. Further prospective studies are needed to confirm the potential of self-care interventions in preventing severe dermatitis.

Background/aim: With the prevalence of COVID-19, the importance of short-course radiotherapy (RT) in many cancers has been discussed. The aim of this study was to evaluate the results of hypofractionated schedule RT for localized gastric mucosa-associated lymphoid tissue (MALT) lymphoma., Patients and Methods: We assessed 45 patients with localized gastric MALT lymphoma who underwent RT between 2005 and 2019. The total RT dose ranged from 24-36 Gy in 10-18 fractions (median of 28 Gy/14 fractions). Patients were divided into three groups according to the dose fractionation: Group A, 30-36 Gy in 15-18 fractions; Group B, 26-28 Gy in 13-14 fractions; and Group C, 24-25 Gy in 10 fractions., Results: All the patients achieved complete remission without local recurrence. The 5-year overall, cause-specific, and progression-free survival rates were 97.5%, 100%, and 97.5%, respectively, with a median follow-up period of 82 months. Among the dose fractionation groups, there were no statistically significant differences in local control or incidence of grade 2 or worse adverse events., Conclusion: Results of RT for localized gastric MALT lymphoma showed excellent local control and survival with no serious adverse events, regardless of dose fractionation. In situations where short-term RT is required, a hypofractionated RT schedule of 24-25 Gy in 10 fractions could be an option for RT schedules., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Previous meta-analysis of conventional radiation therapy for painful bone metastases showed overall response (OR) rates of 72% to 75% (evaluable patients), 61% to 62% (intent-to-treat patients) for initial radiation therapy, and 68% for reirradiation (evaluable patients). However, the definition of pain response differed among the studies included. Hence, we conducted a systematic review and meta-analysis to determine the pain response rates assessed by the International Consensus Pain Response Endpoints (ICPRE) for both initial radiation therapy and reirradiation. The PubMed and Scopus databases were searched for articles published between 2002 and 2021. The inclusion criteria were (1) prospective studies or studies based on prospectively collected data and (2) studies in which pain response was assessed using ICPRE. Our primary outcomes of interest were the OR rates (sum of the complete and partial response rates) for both initial radiation therapy and reirradiation. Of the 6470 articles identified in our database search, 32 and 3 met the inclusion criteria for the analysis of initial radiation therapy and reirradiation, respectively. The OR rates of initial radiation therapy in evaluable patients (n = 4775) and intent-to-treat patients (n = 6775) were 60.4% (95% confidence interval [CI], 55.2-65.4) and 45.4% (95% CI, 38.7-52.4), respectively. The OR rates of reirradiation in evaluable patients (n = 733) and intent-to-treat patients (n = 1085) were 70.8% (95% CI, 15.7-96.9) and 62.2% (95% CI, 5.3-98.0), respectively. Subgroup analyses of initial radiation therapy including the comparison of randomized and nonrandomized studies showed no significant differences in any comparison, indicating similar response rates across different study designs. For initial radiation therapy, we determined the ICPRE-assessed response rates, which were lower than previously reported. The OR and complete response rates should be benchmarks for future randomized and nonrandomized studies. For reirradiation, the wide CIs demonstrate that the response rates based on ICPRE require further investigation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Radiation pneumonitis (RP) is a serious side effect of radiotherapy in patients with locally advanced non-small-cell lung cancer (NSCLC). Image cropping reduces training noise and may improve classification accuracy. This study proposes a prediction model for RP grade ≥ 2 using a convolutional neural network (CNN) model with image cropping. The 3D computed tomography (CT) images cropped in the whole-body, normal lung (nLung), and nLung regions overlapping the region over 20 Gy (nLung∩20 Gy) used in treatment planning were used as the input data. The output classifies patients as RP grade < 2 or RP grade ≥ 2. The sensitivity, specificity, accuracy, and area under the curve (AUC) were evaluated using the receiver operating characteristic curve (ROC). The accuracy, specificity, sensitivity, and AUC were 53.9%, 80.0%, 25.5%, and 0.58, respectively, for the whole-body method, and 60.0%, 81.7%, 36.4%, and 0.64, respectively, for the nLung method. For the nLung∩20 Gy method, the accuracy, specificity, sensitivity, and AUC improved to 75.7%, 80.0%, 70.9%, and 0.84, respectively. The CNN model, in which the input image is segmented in the normal lung considering the dose distribution, can help predict an RP grade ≥ 2 for NSCLC patients after definitive radiotherapy., (© 2023. Australasian College of Physical Scientists and Engineers in Medicine.)

Background/aim: The aim of this study was to investigate the use of spacers and their efficacy in brachytherapy with 198 Au grains for buccal mucosa cancer., Patients and Methods: Sixteen patients with squamous cell carcinoma of the buccal mucosa who were treated with 198 Au grain brachytherapy were included. The distance between 198 Au grains, distance between 198 Au grains and the maxilla or mandible, and the maximum dose/cc to the jawbone (D1cc) with and without a spacer was investigated in three out of 16 patients., Results: The median distance between 198 Au grains without and with a spacer was 7.4 and 10.7 mm, respectively; this was significantly different. The median distance between 198 Au grains and the maxilla without and with a spacer was 10.3 and 18.5 mm, respectively; again this was significantly different. The median distance between 198 Au grains and the mandible without and with a spacer was 8.6 and 17.3 mm, respectively; the difference was significant. The D1cc to the maxilla without and with a spacer were 14.9, 68.7, and 51.8 Gy and 7.5, 21.2, and 40.7 Gy in cases 1, 2, and 3, respectively. The D1cc to the mandible without and with a spacer were 27.5, 68.7, and 85.8 Gy and 11.3, 53.6, and 64.9 Gy in cases 1, 2, and 3, respectively. No osteoradionecrosis of the jaw bones was observed in any case., Conclusion: The spacer enabled maintenance of the distance between 198 Au grains, and between 198 Au grains and the jawbone. In buccal mucosa cancer, using a spacer in brachytherapy with 198 Au grains appears to reduce jawbone complications., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

It remains unclear whether sex differences exist during the development of visceral adipose tissue (VAT) inflammation associated with obesity. The purpose of this study was to clarify sex differences in the occurrence of senescence-related T cells (CD44 high PD-1 + CD4 + ), which play a key role in the progression of VAT inflammation associated with high-fat diet (HFD)-induced obesity. Phase 1 : C57BL/6N mice were fed either a control diet (HFC) or HFD for 5 wk. The area under the curve of the oral glucose-tolerance test (oGTT) was maximal at 15 wk in HFD-fed males and at 21 wk in females. At 17 wk, VAT weights were similar, but an increase in the number of macrophages in the VAT was observed only in HFD-fed males. In addition, the numbers of regulatory and senescence-related T cells were consistently higher in males than in females. Phases 2 and 3 : 6-wk-old female mice were randomly divided into sham operation and bilateral ovariectomy (OVX) groups and fed either an HFC or HFD from 7 wk. OVX mice were subjected to 17β-estradiol releasing or placebo pellet implantation and fed an HFC. Body and VAT weights were higher in the OVX group than in the sham. The number of macrophages did not change in the OVX group with either diet. HFC-fed OVX mice exhibited high senescence-related T cells in the VAT, resembling HFC-fed male mice. This change was abolished by 17β-estradiol replacement. Thus, we demonstrated different accumulation patterns of VAT immune cells between the sexes, revealing a role for estrogen in the appearance of senescence-related T cells. NEW & NOTEWORTHY The accumulation pattern of adipose tissue differs between the sexes; however, it is unclear whether sex differences exist during the development of adipose tissue inflammation and whether estrogen plays a role. We demonstrated sex differences in immune cells' subpopulation of visceral adipose tissue. The proinflammatory environment appeared earlier in males than in females. In addition, our results suggest that estrogen plays a role in visceral adipose tissue inflammation, particularly by regulating the appearance of senescence-related T cells.

Background: 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., Methods: 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., Results: 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., Conclusions: 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., (© 2022. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Background: We evaluated the long-term results of definitive chemoradiotherapy (CRT) with elective nodal irradiation (ENI) using a three-dimensional (3D) planning system for resectable, locally advanced esophageal squamous cell carcinoma (LA-ESCC)., Methods: This retrospective study included 65 patients with LA-ESCC who started CRT between 2006 and 2017. Patients with Stage I-IV LA-ESCC according to the Union for International Cancer Control TNM classification (eighth edition) were included. In stage IV, only supraclavicular lymph node (LN) metastasis was included. All patients received radiotherapy with ENI and concurrent chemotherapy with platinum and 5-fluorouracil., Results: The median age of the patients was 70 years (range 52-83 years). Stage I, II, III, and IV diseases were observed in 3 (5%), 28 (43%), 22 (34%), and 12 patients (18%), respectively. The median prescription dose was 66 Gy (range 50.4-66 Gy). The median follow-up period for the survivors was 71 months (range 8-175 months). The 5-year overall survival (OS) and progression-free survival rates were 54 and 43%, respectively. The 5-year OS rates for stages I-II and III-IV were 67 and 42%, respectively. Recurrence occurred in 29 patients (45%), and recurrence of regional LNs only occurred in 2 patients (3%). Grade 3 or higher late adverse events were observed in 8 patients (12%). Grade 5 heart failure occurred in two patients (3%); both had cardiovascular disease before treatment., Conclusion: The long-term results of definitive CRT with ENI for resectable LA-ESCC were favorable. ENI with a 3D planning system may reduce regional LN recurrence and late adverse events., (© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Appropriate use of radiotherapy leads to a better patient care. Oncologists may wonder when to apply radiotherapy for painful bone metastases, what patients should particularly be offered radiotherapy, when to apply re-irradiation, when to apply radiotherapy to malignant spinal cord compression, or whether to apply radiotherapy to prevent symptoms. This paper aims to offer non-radiation oncologist physicians knowledge to help them better refer patients to radiation oncology.

Purpose: Radiation pneumonitis (RP) is dose-limiting toxicity for non-small-cell cancer (NSCLC). This study developed an RP prediction model by integrating dose-function features from computed four-dimensional computed tomography (4DCT) ventilation using the least absolute shrinkage and selection operator (LASSO)., Methods: Between 2013 and 2020, 126 NSCLC patients were included in this study who underwent a 4DCT scan to calculate ventilation images. We computed two sets of candidate dose-function features from (1) the percentage volume receiving > 20 Gy or the mean dose on the functioning zones determined with the lower cutoff percentile ventilation value, (2) the functioning zones determined with lower and upper cutoff percentile ventilation value using 4DCT ventilation images. An RP prediction model was developed by LASSO while simultaneously determining the regression coefficient and feature selection through fivefold cross-validation., Results: We found 39.3 % of our patients had a ≥ grade 2 RP. The mean area under the curve (AUC) values for the developed models using clinical, dose-volume, and dose-function features with a lower cutoff were 0.791, and the mean AUC values with lower and upper cutoffs were 0.814. The relative regression coefficient (RRC) on dose-function features with upper and lower cutoffs revealed a relative impact of dose to each functioning zone to RP. RRCs were 0.52 for the mean dose on the functioning zone, with top 20 % of all functioning zone was two times greater than that of 0.19 for these with 60 %-80 % and 0.17 with 40 %-60 % (P < 0.01)., Conclusions: The introduction of dose-function features computed from functioning zones with lower and upper cutoffs in a machine learning framework can improve RP prediction. The RRC given by LASSO using dose-function features allows for the quantification of the RP impact of dose on each functioning zones and having the potential to support treatment planning on functional image-guided radiotherapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Introduction/Background: Chemoradiotherapy (CRT) followed by durvalumab, an immune checkpoint inhibitor, is the standard treatment for locally advanced non-small-cell lung cancer (NSCLC). Interstitial lung disease (ILD) is a life-threatening toxicity caused by these treatments; however, risk factors for the ILD have not yet been established. Interstitial lung abnormalities (ILAs) are computed tomography (CT) findings which manifest as minor interstitial shadows. We aimed to investigate whether ILAs could be risk factors for grade-two or higher ILD during durvalumab therapy. Patients and Methods: Patients with NSCLC who received durvalumab after CRT from July 2018 to June 2021 were retrospectively enrolled. We obtained patient characteristics, laboratory data, radiotherapeutic parameters, and chest CT findings before durvalumab therapy. Results: A total of 148 patients were enrolled. The prevalence of ILAs before durvalumab treatment was 37.8%. Among 148 patients, 63.5% developed ILD during durvalumab therapy. The proportion of patients with grade-two or higher ILD was 33.8%. The univariate logistic regression analysis revealed that older age, high dose-volume histogram parameters, and the presence of ILAs were significant risk factors for grade-two or higher ILD. The multivariate analysis showed that ILAs were independent risk factors for grade-two or higher ILD (odds ratio, 3.70; 95% confidence interval, 1.69−7.72; p < 0.001). Conclusions: We showed that pre-existing ILAs are risk factors for ILD during durvalumab treatment after CRT. We should pay attention to the development of grade-two or higher ILD during durvalumab treatment in patients with ILAs.

Background: High-mobility group box 1 (HMGB1) is a pro-inflammatory protein associated with the pathophysiology of lung injury and lung tumorigenesis. Here, we investigated the predictive potential of serum HMGB1 levels for radiation pneumonitis in patients with lung cancer., Methods: This was a retrospective biomarker study of 73 patients with non-small cell lung cancer treated with definitive thoracic radiotherapy between August 2007 and January 2021. We measured HMGB1 levels in serum stored before treatment, and analyzed its association with the development of grade ≥ 2 or grade ≥ 3 radiation pneumonitis. Additionally, baseline characteristics affecting HMGB1 levels were identified., Results: Of the 73 patients, 21 (28.8%) and 6 (8.2%) patients experienced grade 2 and ≥ 3 radiation pneumonitis, respectively. Univariate and multivariate logistic regression analyses revealed that higher baseline levels of serum HMGB1 were significantly associated with a higher risk of grade ≥ 3, but not grade ≥ 2, radiation pneumonitis. The incidence of grade ≥ 3 radiation pneumonitis was higher in patients with HMGB1 levels ≥ 6.2 ng/mL than in those with levels < 6.2 ng/mL (25.0% vs. 3.5%, p = 0.019). Baseline serum levels of HMGB1 were independently and positively associated with gross tumor volume., Conclusions: Higher serum HMGB1 levels were significantly associated with the risk of grade ≥ 3 radiation pneumonitis in patients with lung cancer, and therefore, HMGB1 could be a potential blood biomarker for predicting severe radiation pneumonitis., (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objectives: To develop an imaging prognostic model for idiopathic pulmonary fibrosis (IPF) patients using hybrid auto-segmentation radiomics analysis, and compare the predictive ability between the radiomics analysis and conventional visual score methods., Methods: Data from 72 IPF patients who had undergone CT were analyzed. In the radiomics analysis, quantitative CT analysis was performed using the semi-auto-segmentation method. In the visual method, the extent of radiologic abnormalities was evaluated and the overall percentage of lung involvement was calculated by averaging values for six lung zones. Using a training cohort of 50 cases, we generated a radiomics model and a visual score model. Subsequently, we investigated the predictive ability of these models in a testing cohort of 22 cases., Results: Three significant prognostic factors such as contrast, Idn, and cluster shade were selected by LASSO Cox regression analysis. In the visual method, multivariate Cox regression analysis revealed that honeycombing and reticulation were significant prognostic factors. Subsequently, a predictive nomogram for prognosis in IPF patients was established using these factors. In the testing cohort, the c-index of the visual and radiomics nomograms were 0.68 and 0.74, respectively. When dividing the cohort into high-risk and low-risk groups using the median nomogram score, significant differences in overall survival (OS) in the visual and radiomics models were observed (P=0.000 and P=0.0003, respectively)., Conclusions: The prediction model with hybrid radiomics analysis had a better ability to predict OS in IPF patients than that of the visual method., Competing Interests: None, (© 2022 The Author(s).)

Background: Stereotactic body radiotherapy (SBRT) is a promising approach in treating painful bone metastases. However, the superiority of SBRT over conventional external beam radiotherapy (cEBRT) remains controversial. Therefore, this systematic review and meta-analysis of randomised controlled trials was conducted to compare SBRT and cEBRT for the treatment of bone metastases., Methods: A search was conducted using PubMed on January 22, 2022, with the following inclusion criteria: (i) randomised controlled trials comparing SBRT with cEBRT for bone metastases and (ii) endpoint including pain response. Effect sizes across studies were pooled using random-effects models in a meta-analysis of risk ratios., Results: A total of 1246 articles were screened, with 7 articles comprising 964 patients (522 and 442 patients in the SBRT and cEBRT arms, respectively) meeting the inclusion criteria. The overall pain response (OR) rates of bone metastases at 3 months were 45% and 36% in the SBRT and cEBRT arms, respectively. The present analyses showed no significant difference between the two groups. In four studies included for the calculation of OR rates of spinal metastases at three months, the OR rates were 40% and 35% in the SBRT and cEBRT arms, respectively, with no significant difference between the two groups. The incidence of severe adverse effects and health-related quality of life outcomes were comparable between the two arms., Conclusions: The superiority of SBRT over cEBRT for pain palliation in bone metastases was not confirmed in this meta-analysis. Although SBRT is a standard of care for bone metastases, patients receiving SBRT should be selected appropriately., (© 2022. The Author(s).)

Objective: We aimed to develop a predictive model for occult cervical lymph node metastasis in patients with tongue cancer using radiomics and machine learning from pretreatment contrast-enhanced computed tomography., Study Design: This study included 161 patients with tongue cancer who received local treatment. Computed tomography images were transferred to a radiomics platform. The volume of interest was the total neck node level, including levels Ia, Ib, II, III, and IVa at the ipsilateral side, and each neck node level. The dimensionality of the radiomics features was reduced using least absolute shrinkage and selection operator logistic regression analysis. We compared 5 classifiers with or without the synthetic minority oversampling technique (SMOTE)., Results: For the analysis at the total neck node level, random forest with SMOTE was the best model, with an accuracy of 0.85 and an area under the curve score of 0.92. For the analysis at each neck node level, a support vector machine with SMOTE was the best model, with an accuracy of 0.96 and an area under the curve score of 0.98., Conclusions: Predictive models using radiomics and machine learning have potential as clinical decision support tools in the management of patients with tongue cancer for prediction of occult cervical lymph node metastasis., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: This study aimed to investigate status of displacement of gold-198 ( 198 Au) grains in patients with oral cancers as well as factors and countermeasures for the displacement of 198 Au grains., Material and Methods: The present study included 34 patients with oral cancers, who were exclusively treated with 198 Au grain brachytherapy between 2013 and 2019. Timing and duration of the 198 Au grain displacement from the oral cavity and reduction in radiation dose were estimated. Location of the displaced grain was classified as either inside or outside of gross tumor volume. Number and location of the displacement of 198 Au grains, primary lesion, and growth type were evaluated., Results: Of the 34 patients included in this study, 198 Au grains were displaced in 4 patients (11.8%) during hospitalization. A total of 5 grains (1.4%) were displaced out of an overall count of 367 grains implanted in these 34 patients. Of the four patients who experienced displacement of 198 Au grains, three had tongue cancer, and one had lip cancer. All four patients whose grains were displaced had superficial lesions., Conclusions: When performing brachytherapy with 198 Au grains for superficial lesions on the tongue or lips, care should be taken to avoid grain displacement., Competing Interests: The authors report no conflict of interest., (Copyright © 2022 Termedia.)

Background/aim: We investigated treatment outcomes and complications during reirradiation of patients with oral cancers., Patients and Methods: Six patients who received definitive radiotherapy for oral cancer as the initial treatment and brachytherapy for recurrence were included. Local control and overall survival rates, soft tissue and mandibular complications, and tooth extraction were investigated., Results: The five-year local control and overall survival rates were 83.3% and 100%, respectively. The occurrence rate of grade 2 soft tissue and mandible complications was 33.3%, and the primary sites were the buccal mucosa and the floor of mouth. The positions of the extracted tooth in the two cases were adjacent to the tumor, and one case developed grade 2 complication of the mandible., Conclusion: During recurrence of the buccal mucosa and the floor of mouth cancers, reirradiation should be avoided considering mandibular complications. To avoid reirradiation-related complications, tooth extraction near the radiation field should be avoided., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: This study aimed to retrospectively evaluate the radiation dose and complications in soft tissue and mandible caused by 198 Au grain brachytherapy alone or the combination with other modalities in patients with the cancer of the floor of the mouth., Materials and Methods: Twelve patients with T1 (n = 5) and T2 (n = 7) squamous cell carcinoma of the floor of the mouth, who were treated with 198 Au grain brachytherapy alone (n = 5) or the combination of external beam radiotherapy (EBRT) and/or chemotherapy and 198 Au grain brachytherapy (n = 7) from January 2005 to December 2016, were included. The relationships between the radiation dose and the complications of the soft tissue or mandible were investigated., Results: Seven of 12 patients had died. Of these 7 patients, one with T1 and 2 with T2 had died of the causes related to the cancer of the floor of the mouth. Two with T1 and 2 with T2 had died of other diseases. Two patients had grade 2 complications of the soft tissue and mandible. These patients were treated by the combination of EBRT and/or chemotherapy and 198 Au grain brachytherapy and irradiated with 123 or 139 Gy in total dose, respectively. And one of these patients was treated by the chemotherapy in addition to EBRT., Conclusion: Our study showed that the combination of EBRT and 198 Au grains brachytherapy for the floor of the mouth cancer patients might be associated with risks of developing complications of soft tissue ulcer and mandibular bone necrosis., (© 2021. The Author(s), under exclusive licence to Japanese Society for Oral and Maxillofacial Radiology and Springer Nature Singapore Pte Ltd.)

Background and Purpose: Radiotherapy (RT) has recently received increasing attention as an additional treatment for organ preservation after non-curative endoscopic submucosal dissection (ESD) in patients with superficial esophageal cancer. Esophageal stenosis is an adverse event related to RT after ESD that is not widely studied. The aim of this study was to investigate esophageal stenosis related to salvage RT in superficial esophageal cancer after non-curative ESD., Materials and Methods: Fifty patients who received salvage RT after non-curative ESD at a single institution between 2011 and 2018 were included in this study. The Common Terminology Criteria for Adverse Events, version 5.0, was used to assess esophageal stenosis. Data were compared using Fisher's exact test. Statistical significance was set at P < 0.05., Results: Median follow-up time was 48 months (range, 12-95 months). Grade 2 and 3 esophageal stenosis were observed in 17 (34%), and 3 patients (6%), respectively. The frequency of grade 2 or worse esophageal stenosis decreased over time (before RT, 6 months, 1 year, and 2 years after RT: 16 (32%), 13 (26%), 10 (20%), and 6 (12%) patients, respectively). Only one patient required endoscopic balloon dilation (EBD) 1 year after RT. All grade 3 esophageal stenosis improved grade 2 or less by EBD. In univariate analysis, only tumor location was a significant risk factor for grade 3 esophageal stenosis., Conclusions: Esophageal stenosis, after salvage RT in patients with esophageal cancer who received non-curative ESD, improved naturally or after EBD; only a few cases required long-term EBD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The use of volumetric modulated arc therapy is gradually widespread for locally advanced non-small cell lung cancer. The purpose of this study was to identify the factors that caused ≥ grade 2 radiation pneumonitis and evaluate the impact of using volumetric modulated arc therapy on the incidence of ≥ grade 2 radiation pneumonitis by comparing three-dimensional conformal radiation therapy., Methods: We retrospectively evaluated 124 patients who underwent radical radiotherapy for locally advanced non-small cell lung cancer in our institution between 2008 and 2019. The following variables were analysed to detect the factors that affected ≥ grade 2 radiation pneumonitis; age, sex, the presence of interstitial lung disease, pulmonary emphysema, tumour location, stage, PTV/lung volume, lung V20Gy, total dose, concurrent chemoradiotherapy, adjuvant immune checkpoint inhibitor, radiotherapy method. Radiation pneumonitis was evaluated using the common terminology criteria for adverse events (version 5.0)., Results: A total of 84 patients underwent three-dimensional conformal radiation therapy (3D-CRT group) and 40 patients underwent volumetric modulated arc therapy (VMAT group). The cumulative incidence of ≥ grade 2 radiation pneumonitis at 12 months was significantly lower in the VMAT group than in the 3D-CRT group (25% vs. 49.1%). The use of volumetric modulated arc therapy was a significant factor for ≥ grade 2 radiation pneumonitis (HR:0.32, 95% CI: 0.15-0.65, P = 0.0017) in addition to lung V20Gy (≥ 24%, HR:5.72 (95% CI: 2.87-11.4), P < 0.0001) and total dose (≥ 70 Gy, HR:2.64 (95% CI: 1.39-5.03), P = 0.0031) even after adjustment by multivariate analysis., Conclusions: We identified factors associated with ≥ grade 2 radiation pneumonitis in radiotherapy for patients with locally advanced non-small cell lung cancer. Volumetric modulated arc therapy has potential benefits to reduce the risk of ≥ grade 2 radiation pneumonitis., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

It is often challenging to determine the accurate size and shape of oral lesions through computed tomography (CT) or magnetic resonance imaging (MRI) when they are very small or obscured by metallic artifacts, such as dental prostheses. Intraoral ultrasonography (IUS) has been shown to be beneficial in obtaining precise information about total tumor extension, as well as the exact location and guiding the insertion of catheters during interstitial brachytherapy. We evaluated the role of IUS in assessing the clinical outcomes of interstitial brachytherapy with 198Au grains in tongue cancer through a retrospective medical chart review. The data from 45 patients with T1 (n = 21) and T2 (n = 24) tongue cancer, who were mainly treated with 198Au grain implants between January 2005 and April 2019, were included in this study. 198Au grain implantations were carried out, and positioning of the implants was confirmed by IUS, to ensure that 198Au grains were appropriately placed for the deep border of the tongue lesion. The five-year local control rates of T1 and T2 tongue cancers were 95.2% and 95.5%, respectively. We propose that the use of IUS to identify the extent of lesions and the position of implanted grains is effective when performing brachytherapy with 198Au grains., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

To predict grade ≥ 2 radiation pneumonitis (RP) in patients with locally advanced non-small cell lung cancer (NSCLC) using multi-region radiomics analysis. Data from 77 patients with NSCLC who underwent definitive radiotherapy between 2008 and 2018 were analyzed. Radiomic feature extraction from the whole lung (whole-lung radiomics analysis) and imaging- and dosimetric-based segmentation (multi-region radiomics analysis) were performed. Patients with RP grade ≥ 2 or < 2 were classified. Predictors were selected with least absolute shrinkage and selection operator logistic regression and the model was built with neural network classifiers. A total of 49,383 radiomics features per patient image were extracted from the radiotherapy planning computed tomography. We identified 4 features and 13 radiomics features in the whole-lung and multi-region radiomics analysis for classification, respectively. The accuracy and area under the curve (AUC) without the synthetic minority over-sampling technique (SMOTE) were 60.8%, and 0.62 for whole-lung and 80.1%, and 0.84 for multi-region radiomics analysis. These were improved 1.7% for whole-lung and 2.1% for multi-region radiomics analysis with the SMOTE. The developed multi-region radiomics analysis can help predict grade ≥ 2 RP. The radiomics features in the median- and high-dose regions, and the local intensity roughness and variation were important factors in predicting grade ≥ 2 RP., (© 2021. The Author(s).)

Aging is associated with functional decline in the immune system and increases the risk of chronic diseases owing to smoldering inflammation. In the present study, we demonstrated an age-related increase in the accumulation of Programmed Death-1 (PD-1)+ memory-phenotype T cells that are considered "senescence-associated T cells" in both the visceral adipose tissue and spleen. As caloric restriction is an established intervention scientifically proven to exert anti-aging effects and greatly affects physiological and pathophysiological alterations with advanced age, we evaluated the effect of caloric restriction on the increase in this T-cell subpopulation and glucose tolerance in aged mice. Long-term caloric restriction significantly decreased the number of PD-1+ memory-phenotype cluster of differentiation (CD) 4+ and CD8+ T cells in the spleen and visceral adipose tissue, decreased M1-type macrophage accumulation in visceral adipose tissue, and improved insulin resistance in aged mice. Furthermore, the immunological depletion of PD-1+ T cells reduced adipose inflammation and improved insulin resistance in aged mice. Taken together with our previous report, these results indicate that senescence-related T-cell subpopulations are involved in the development of chronic inflammation and insulin resistance in the context of chronological aging and obesity. Thus, long-term caloric restriction and specific deletion of senescence-related T cells are promising interventions to regulate age-related chronic diseases., Competing Interests: The authors have declared that no competing interests exist.

Background: This study aimed to propose a machine learning model to predict the local response of resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) treated by neoadjuvant chemoradiotherapy (NCRT) using pretreatment 18-fluorodeoxyglucose positron emission tomography (FDG PET) images., Methods: The local responses of 98 patients were categorized into two groups (complete response and noncomplete response). We performed a radiomics analysis using five segmentations created on FDG PET images, resulting in 4250 features per patient. To construct a machine learning model, we used the least absolute shrinkage and selection operator (LASSO) regression to extract radiomics features optimal for the prediction. Then, a prediction model was constructed by using a neural network classifier. The training model was evaluated with 5-fold cross-validation., Results: By the LASSO analysis of the training data, 22 radiomics features were extracted. In the testing data, the average accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve score of the five prediction models were 89.6%, 92.7%, 89.5%, and 0.95, respectively., Conclusions: The proposed machine learning model using radiomics showed promising predictive accuracy of the local response of LA-ESCC treated by NCRT.

Preoperative chemoradiotherapy with capecitabine or 5-fluorouracil is a standard treatment for locally advanced rectal cancer (LARC). S-1, a prodrug of 5-fluorouracil, is a candidate for this chemoradiotherapy regimen in Japan; however, treatment outcomes after S-1 treatment alone are not clear. This study aimed to assess the efficacy and tolerability of preoperative chemoradiotherapy with S-1 alone for LARC. We retrospectively evaluated 54 LARC patients who underwent preoperative chemoradiotherapy with S-1 alone in our institution between 2005 and 2017. The clinical tumor stage was cT2-3 in 31 patients and cT4 in 23 patients, and lymph node metastases were clinically evident in 31 patients. S-1, at a dose of 80 mg/m2/day, was orally administered during radiotherapy. A total dose of 45-50.4 Gy was delivered in 25-28 fractions (median: 50.4 Gy). Surgical resections were scheduled 6-10 weeks after chemoradiotherapy completion. The 3- and 5-year overall survival rates were 92.4 and 72.8%, respectively, with a median follow-up time of 51 months. The 3- and 5-year local control rates were 96.2 and 85.9%, respectively. A pathological complete response was observed in 7 patients (13.0%) at the time of surgery. Ten patients (18.5%) had grade 3 acute toxicities and 5 patients (9.3%) had grade 3 late toxicities. No grade 4 or 5 toxicities were observed. Preoperative chemoradiotherapy with S-1 alone followed by total mesorectal excision resulted in a low incidence of toxicities and comparable clinical results. Therefore, S-1 alone can be a treatment option for preoperative chemoradiotherapy in LARC patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Background: Although metastatic tumors in lymph nodes (LN) are potentially affected by neoadjuvant chemoradiotherapy (NCRT), the distribution of LN metastases of esophageal squamous cell carcinoma (ESCC) after trimodal therapy has never been sufficiently estimated., Patients and Methods: We evaluated the distribution of LN metastases, relationships between LN metastases and radiation fields, risk factors for LN metastasis, and the influence of LN metastasis on the survival of 184 patients with ESCC who underwent NCRT followed by esophagectomy., Results: Neoadjuvant chemoradiotherapy resulted in down-staged LN status in 74 (49.3%) patients. Pathological LN metastases were extensive in 177 LN stations in the cervical, mediastinal, and abdominal fields, and 162 (91.5%) metastases were located inside the radiation fields. Multivariate analysis showed that clinical N stage [N0 vs. 1/2/3: hazard ratio (HR), 2.69; 95% confidence interval (CI), 1.22-5.92; p = 0.01] and clinical response of primary tumor (complete vs. noncomplete: HR, 2.93; 95% CI, 1.50-5.69; p = 0.002) were statistically significant for pathological LN metastasis. Recurrence-free and overall survivals were significantly stratified according to the number of pathological LN metastases, associations between clinical and pathological LN metastases, and presence or absence of pathological LN metastases outside radiation field., Conclusions: About 50% of patients who were clinically diagnosed with LN metastasis before treatment were downstaged by NCRT, and their prognoses were relatively good. However, LN metastases were extensive at the cervical, mediastinal, and abdominal areas, even within the radiation field. Thus, systematic and adequate lymphadenectomy is required for ESCC treated by NCRT.

In this work, individual radiosensitivity was evaluated using DNA damage response and chromosomal aberrations (CAs) in peripheral blood lymphocytes (PBLs) for the prediction of acute toxicities of chemoradiotherapy (CRT) in esophageal cancer patients. Eighteen patients with esophageal cancer were enrolled in this prospective study. Prescribed doses were 60 Gy in 11 patients and 50 Gy in seven patients. Patients received 2 Gy radiotherapy five days a week. PBLs were obtained during treatment just before and 15 min after 2 Gy radiation therapy on the days when the cumulative dose reached 2, 20, 40 Gy and 50 or 60 Gy. PBLs were also obtained four weeks and six months after radiotherapy in all and 13 patients, respectively. Dicentric and ring chromosomes in PBLs were counted to evaluate the number of CAs. Gamma-H2AX foci per cell were scored to assess DNA double-strand breaks. We analyzed the association between these factors and adverse events. The number of γ-H2AX foci before radiotherapy showed no significant increase during CRT, while their increment was significantly reduced with the accumulation of radiation dose. The mean number of CAs increased during CRT up to 1.04 per metaphase, and gradually decreased to approximately 60% six months after CRT. Five patients showed grade 3 toxicities during or after CRT (overreactors: OR), while 13 had grade 2 or less toxicities (non-overreactors: NOR). The number of CAs was significantly higher in the OR group than in the NOR group at a cumulative dose of 20 Gy (mean value: 0.63 vs. 0.34, P = 0.02), 40 Gy (mean value: 0.90 vs. 0.52, P = 0.04), and the final day of radiotherapy (mean value: 1.49 vs. 0.84, P = 0.005). These findings suggest that number of CAs could be an index for predicting acute toxicities of CRT for esophageal cancer., (©2021 by Radiation Research Society. All rights of reproduction in any form reserved.)

Purpose: The T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign was previously reported as a diagnostic indicator of diffuse astrocytoma, isocitrate dehydrogenase-mutant, and 1p/19q noncodeletion. Subsequently, it was reported that the same findings were observed in diffuse intrinsic pontine glioma (DIPG). We investigated the clinical significance of T2-FLAIR mismatch sign in DIPG., Methods: Twenty-one patients with DIPG (Male: Female = 12:9) were treated at our institute between 2004 and 2019. All patients were treated with local radiotherapy of 54 Gy/30 fractions. The positive T2-FLAIR mismatch sign was defined if it fulfilled the following criteria: (1) T2-FLAIR mismatch volume was >50% of T2 high volume at nonenhanced area, (2) the FLAIR low lesion is not associated with gadolinium enhancement (inside of enhancement or just outside of enhancement defined as edema), and (3) signal-intensity of FLAIR lowest lesion at tumor is lower than the normal cerebellar cortex., Results: In our patient series, T2-FLAIR mismatch sign was found in 5 out of 21 patients. Objective response rate of radiotherapy was 100% in patients positive for T2-FLAIR mismatch, while it was 25.0% in patients negative for T2-FLAIR mismatch, and this difference was statistically significant (p < 0.01, Fisher's exact test). In patients under the age of 18-years, T2-FLAIR mismatch positive had a slightly better prognosis (p < 0.05, Wilcoxon test)., Conclusion: T2-FLAIR mismatch sign in DIPG may be an indicator for better response to radiotherapy and a better prognostic factor., (© 2021 S. Karger AG, Basel.)

Purpose: The present study aimed to evaluate the long-term results of definitive chemoradiotherapy (CRT) for unresectable locally advanced esophageal squamous cell carcinoma (LA-ESCC)., Materials and Methods: We analyzed eighty patients with unresectable LA-ESCC, who underwent definitive CRT between 2001 and 2014. The 5-year overall survival (OS), cause-specific survival (CSS), and progression-free survival (PFS) rates were calculated, and we investigated the prognostic factors and adverse events., Results: The median age was 66 years (range, 41-83 years). Histologically, all patients had squamous cell carcinoma. The most common tumor site was the middle thoracic esophagus in 43 (54%) patients. According to the eighth edition of the Union for International Cancer Control TNM classification, sixty-six patients (83%) had T4 disease, 59 (74%) had regional lymph node (LN) metastases, and 35 (44%) had distant LN metastases beyond the regional LN (M1 LYM) disease. Forty-five (56%) and 35 (44%) patients belong to clinical stages IVA and IVB, respectively. The median follow-up period for survivors was 86 months. The 5-year OS, CSS, and PFS rates were 20.2%, 25.7%, and 18.4%, respectively. On univariate analysis, only the performance status score was significantly associated with better overall survival (p = 0.026). Grade 3 or higher late adverse events were observed in 12 (15%) patients, and these included cardiopulmonary adverse events in 6 (8%) patients. Treatment-related death occurred in 3 (4%) patients., Conclusion: We showed the long-term results of definitive CRT for unresectable LA-ESCC. The survivals are still poor and new treatment strategies need to be developed., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

The present study aimed to analyze treatment outcomes after induction chemotherapy followed by chemoradiotherapy (CRT) using volumetric-modulated arc therapy (VMAT) in patients with stage IVA-B oropharyngeal cancer (OPC) or hypopharyngeal cancer (HPC), with long-term observation, including examination of larynx preservation. A total of 60 patients with stage IVA-B OPC or HPC, who underwent induction TPF chemotherapy (a combination regimen consisting of docetaxel, cisplatin, and 5-fluorouracil) followed by CRT using VMAT were analyzed. Overall survival (OS), progression-free survival (PFS), laryngoesophageal dysfunction-free survival (LEDFS), and locoregional control (LRC) were calculated and compared. Univariate and multivariate analyses were performed to determine statistical differences in OS and LEDFS. The median follow-up period at the time of evaluation was 61 months. Twenty-six (43%) patients had OPC and 34 (57%) had HPC. The 5-year OS, PFS, LEDFS, and LRC rates were 57%, 52%, 52%, and 68%, respectively. Response to TPF therapy was the only significant predictive factor of OS and LEDFS in multivariate analyses. Regarding long-term toxicities, grade ≥ 2 late toxicities accounted for 15%. No patients experienced grade ≥ 3 xerostomia, and 5% of all patients developed grade 3 dysphagia. With long-term observation, the OS, PFS, and LEDFS rates were relatively good, and the incidence of late toxicities was low. TPF followed by CRT using VMAT was feasible and more effective in those who responded to induction chemotherapy., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Background/aim: The present study aimed to analyze the treatment outcome after definitive radiotherapy (dRT) using volumetric-modulated arc therapy (VMAT) in patients with hypopharyngeal cancer (HPC), including an examination of late toxicities., Patients and Methods: A total of 62 patients with HPC, who underwent dRT using VMAT, were analyzed. Overall survival (OS), progression-free survival (PFS), laryngoesophageal dysfunction-free survival (LEDFS), and locoregional control (LRC) were calculated., Results: The median follow-up period was 49 months. The 3- and 5-year OS, PFS, LEDFS, and LRC rates were 77% and 60%, 61% and 56%, 66% and 53%, and both 79%, respectively. Regarding late toxicities, 11 (17.7%) patients developed grade ≥2 late toxicity. Grade 3 dysphagia was observed in 4 (6.5%) patients, and grade 2 xerostomia in 6 (9.7%)., Conclusion: VMAT was an effective treatment for HPC, with a low incidence of late toxicities., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Endoscopic resection is widely used as an effective treatment for superficial esophageal cancer. However, the risk of lymph node metastasis increases in cases of muscularis mucosae or deeper invasion, for which additional treatment such as radiotherapy or surgery is required. Accordingly, the current study investigated the efficacy and toxicity of salvage radiotherapy after non-curative endoscopic resection as an organ preservation strategy., Methods: We retrospectively reviewed 37 esophageal cancer patients who received salvage radiotherapy after non-curative endoscopic resection. The pathological invasion depths were the muscularis mucosae, submucosal layer, and muscularis propria in 14, 22, and one patient, respectively. All patients received external beam radiotherapy. Among them, eight received intraluminal brachytherapy following external beam radiotherapy. Elective nodal irradiation was administered to all patients. Twenty-five patients received concurrent platinum and fluorouracil-based chemotherapy., Results: The median follow-up time was 74 months (range: 3-212). The 5-year progression-free survival and overall survival rates were 64 and 78%, respectively. No local or regional lymph node recurrence was observed. The causes of death included esophageal cancer in one patient, metachronous esophageal cancer in one patient, other malignancies in eight patients, and other causes in six patients. Late cardiac toxicities ≥ grade 3 were observed in six patients, one of whom died of arrhythmia., Conclusions: Salvage radiotherapy after non-curative esophageal endoscopic resection is an effective treatment as an organ preservation strategy. Although muscularis mucosae and submucosal cancer have a high risk of lymph node metastasis, our results suggest that elective nodal irradiation contributes to reduced regional node metastases.

Introduction : According to several guidelines, stereotactic body radiation therapy (SBRT) for early hepatocellular carcinoma (HCC) can be considered an alternative to other modalities, such as resection, radiofrequency ablation (RFA), and transarterial chemoembolization (TACE), or when these therapies have failed or are contraindicated. This article reviews the current status of SBRT for the treatment of HCC. Areas covered : From the results of many retrospective reports, SBRT is a promising modality with an excellent local control of almost 90% at 2-3 years and acceptable toxicities. Currently there are no randomized trials to compare SBRT and other modalities, such as resection, RFA, and TACE, but many retrospective reports and propensity score matching have shown that SBRT is comparable to the different modalities. Repeated SBRT for intra-hepatic recurrent HCC also resulted in high local control with safety and satisfactory overall survival, which were comparable to those of other curative local treatments. Expert opinion : Despite the good results of SBRT, the conclusions of the comparisons of SBRT and other modalities are still controversial. Further studies, including randomized phase III studies to define that patients are more suitable for each curative local treatment, are needed.