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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.

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.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.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.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.

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 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.

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.

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.

This study aimed to retrospectively evaluate the radiation dose and complications in soft tissue and mandible caused by 198Au grain brachytherapy alone or the combination with other modalities in patients with the cancer of the floor of the mouth. Twelve patients with T1 (n = 5) and T2 (n = 7) squamous cell carcinoma of the floor of the mouth, who were treated with 198Au grain brachytherapy alone (n = 5) or the combination of external beam radiotherapy (EBRT) and/or chemotherapy and 198Au 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. 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 198Au 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. Our study showed that the combination of EBRT and 198Au 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.

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.

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.

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.

This study aimed to evaluate the relationship between cardiac toxicity after definitive chemoradiotherapy (CRT) for esophageal cancer and the dose–volume histogram (DVH) of organs at risk (OARs) [using biological effective dose (BED)]. We analyzed the data of 83 patients with esophageal cancer treated using definitive CRT between 2001 and 2016. Furthermore, we evaluated pericardial effusion (PE) as a measure of cardiac toxicity. The median total irradiation dose was 60 (50.4–71) Gy. Symptomatic PE was observed in 12 (14%) patients. The heart and pericardium V5–V100-BED were significantly higher in patients with symptomatic PE than in those without symptomatic PE (heart: V5–V95-BED, P

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).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.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).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.

We investigated treatment outcomes and complications during reirradiation of patients with oral cancers.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.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.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.

This study aimed to investigate status of displacement of gold-198 (The present study included 34 patients with oral cancers, who were exclusively treated withOf the 34 patients included in this study,When performing brachytherapy with

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.

This study aimed to analyze the clinical results of radiotherapy for cervical cancer using two-dimensional (2D) intracavitary brachytherapy (ICBT) and computed tomography (CT)-based image-guided brachytherapy (IGBT) at our institution. Patients with stage IB–IVA cervical cancer who received ICBT between April 2008 and April 2014 were included in this study. In total 58 patients were assessed. The first 38 patients received ICBT with the 2D treatment plan (the 2D group), and the remaining 20 patients received CT-based IGBT (the IGBT group). The dose of point A tended to be lower in the IGBT group (mean value, 60.6 Gy vs. 62.5 Gy; p = .07), though the minimum dose to the 90% (D90) of the clinical target volume (CTV) was equivalent in both groups (mean value, 66.0 Gy vs. 66.2 Gy; p = .91). The rectum minimum dose to 2 cc (D2cc) was significantly lower in the IGBT group than in the 2D group (mean value, 61.2 Gy vs. 69.1 Gy; p = .001). With a median follow-up time of 60 months, the 5-year local control rates (LCRs) of the IGBT group and 2D group were 100% and 83%, respectively (p = .12). The 5-year incidence of rectal complications in the IGBT group and the 2D group were 11% and 29%, respectively (p = .26). Our study showed favorable LCR and preferred incidence of rectal complications in patients treated with CT-based IGBT., Highlights • The difference of the treatment results between 2D and 3D brachytherapy was analyzed. • The rectum D2cc was significantly lower in the IGBT group compared with the 2D group. • Local control rates tended to be better in the IGBT group than in the 2D group. • The incidence of rectal complications tended to be lower in the IGBT group.

In November 2011, a 61-year-old woman was diagnosed with squamous cell carcinoma (SCC) of the cervix in a uterus didelphys with vaginal septum. The patient was diagnosed with Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) stage IIB because of infiltration to the left parametrium without infiltration to the pelvic wall. The patient was treated with external-beam radiotherapy (EBRT) and brachytherapy (BT), using concomitant chemotherapy with cisplatin. A total of 50 Gy were delivered (2 Gy/fraction/day) to the pelvis, with a central shield after 40 Gy. The patient was treated four times with BT (6 Gy × 4 fractions), with tandem and ovoid applicators inserted once to the left side; tandem to the left side and ovoid bilaterally were inserted twice; and tandem to the right side and ovoid bilaterally were inserted once. Six years and 8 months after the start of treatment, the patient had had no relapse or severe late adverse effects. For accurate diagnosis and optimal treatment of the uterus didelphys, careful interview and pelvic examination at initial diagnosis of a patient are very important.

8528 Background: The standard treatment for locally advanced non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT) followed by treatment of durvalumab, one of immune checkpoint inhibitors (ICI). Interstitial lung disease (ILD) is a clinically life-threatening toxicity of CRT or durvalumab. The patient-characteristics or dose-volume histogram parameters of radiotherapy have been reported to be the risk factors for radiation-induced pneumonitis. However, the risk factors for ILD during durvalumab therapy has not been established. Interstitial lung abnormalities (ILA) are generated by aging or smoking, and manifest as minor interstitial shadow on lung computed tomography (CT). We previously reported that ILA were risk factors for ICI-induced ILD in patients with advanced NSCLC, as well as non-lung cancer. Therefore, we investigated whether ILA could be risk factors for ILD during the durvalumab therapy. Methods: We retrospectively enrolled NSCLC patients who received durvalumab after CRT at 10 institutions from July 2018 to June 2021. Patient-information, patient-characteristics, dose-volume histogram parameters, chest CT findings, and laboratory data, were obtained. CT findings were examined using CT obtained after CRT and prior to durvalumab therapy. Results: A total of 153 patients were enrolled, and the prevalence of ILA was 37.8% (56 patients) before durvalumab treatment. Among the enrolled patients, 94 (63.5%) developed ILD during durvalumab therapy. The proportion of patients with grade 1, grade 2, or grade 3 ILD was observed to be 29.7% (44 patients), 25.7% (38 patients), and 8% (12 patients), respectively. Univariate logistic regression analysis revealed that higher age, higher dose volume histogram parameters (V5, V20, mean lung dose), and the presence of ILA were significant risk factors for grade 2 or more ILD. Multivariate logistic regression analysis showed that ILA, especially ground grass attenuation in ILA, was an independent risk factor for grade 2 or more ILD (odds ratio: 7.02, 95% CI: 2.95-16.69, p < 0.0001). Conclusions: Pre-existing ILA are risk factors for ILD during durvalumab treatment after CRT. This observation is consistent with previously reported findings in patients with advanced lung cancer and non-lung cancer. Therefore, we should pay more attention to the development of grade 2 or more ILD during durvalumab treatment in patients with ILA.

Objective To predict grade 2 radiation pneumonitis (RP) in locally advanced non-small cell lung cancer (NSCLC) patients with high accuracy by using multi-region radiomics analysis.Material and Methods Data from 77 patients with NSCLC who underwent definitive radiotherapy from 2008 to 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. The data were split into 2 sets: 54 tumors for model training and 23 tumors for model testing. Patients with RP grade ≥2 or RP grade Results A total of 49383 radiomics features per patient image were extracted from the radiotherapy planning computed tomography scan. We identified 4 features selected in the whole-lung radiomics analysis and 13 radiomics features selected in the multi-region radiomics analysis for the classification. Out of 13 features, the median and high-dose region were selected from the shape analysis. The features of local intensity roughness and variation were selected from the statistical and texture analysis. The accuracy, specificity, sensitivity, and AUC were 80.1%, 79.2%, 88.9%, and 0.84 for our new method of multi-region radiomics analysis, respectively, which was improved from 60.8%, 64.6%, 53.8%, and 0.62 for whole-lung radiomics analysis. Conclusions The developed multi-region radiomics analysis can help predict grade 2 RP for NSCLC after definitive radiotherapy. The radiomics features in the median- and high-dose regions, and that of local intensity roughness and variation were important factors in predicting grade 2 RP.

This study aimed to retrospectively evaluate the radiation dose and complications in soft tissue and mandible caused byTwelve patients with T1 (n = 5) and T2 (n = 7) squamous cell carcinoma of the floor of the mouth, who were treated withSeven 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 andOur study showed that the combination of EBRT and

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.

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.

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.

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. 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. 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. 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.

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.

Purpose/Objective(s) Whole pelvis irradiation (WPI) is the standard radiation technique for locally advanced cervical cancer without para-aortic lymph node (PALN) metastasis. PALN is one of the most common late failure sites in patients treated with WPI. Although there are several reports about the utility of prophylactic extended-field irradiation (EFI), it is still controversial which patients benefit from prophylactic EFI. If we could predict a PALN metastasis from pre-treatment imaging data, it might help patients to select prophylactic EFI. This study aimed to construct a predictive model for the PALN metastasis in patients with cervical cancer by radiomics analysis using pretreatment magnetic resonance imaging (MRI) of the primary tumor. Materials/Methods Data of 94 patients with cervical squamous cell carcinoma who underwent radiotherapy between 2003/10 and 2018/2 were split into two sets: 66 patients for the training/validation and 28 patients for testing. The PALN status was classified into two groups (positive or negative). Both the synchronous and metachronous PALN metastasis was classified as PALN positive. A total number of 9394 radiomics features per a patient image were extracted from T1- and T2-weighted MRI images. The set of candidate predictors were selected with the least absolute shrinkage and selection operator (LASSO) logistic regression and build predictive models with neural network classifiers were used. The precision, accuracy, and sensitivity by generating confusion matrices and the areas under the receiver operating characteristic curve (AUC) for each model were evaluated. Results By the LASSO analysis of the training/validation data, we found 9 radiomics features from T1-weighted MRI image and 61 radiomics features from T2-weighted MRI image for the classification. The accuracy, specificity, sensitivity, and AUC of the prediction model for the dataset in testing group were 67.9 %, 91.0%, 10.0%, and 0.60 with T1-weighted MRI image, 95.7%, 97.0%, 92.5%, and 0.98 with T2-weighted MRI image, 96.4%, 99.0%, 90.7%, and 0.99 with the combination of T1 and T2-weighted MRI images, respectively. Conclusion We constructed a model to predict the PALN metastasis in patients with cervical cancer using pre-treatment MRI image-based radiomics and machine learning. The model based on T2-weighted image or combination of T1 and T2-wighted MRI image showed promising prediction accuracy. This model may be useful to select patients who benefit from prophylactic EFI. Author Disclosure I. Nishibuchi: None. D. Kawahara: None. M. Kawamura: None. K. Kubo: None. N. Imano: None. Y. Takeuchi: None. A. Saito: None. Y. Murakami: None. Y. Nagata: None.

PURPOSE/OBJECTIVE(S) Although the use of volumetric modulated arc therapy (VMAT) is widespread, there are few reports on the impact of using VMAT on radiation pneumonitis (RP) in radiotherapy for locally advanced non-small cell lung cancer (NSCLC) patients especially for Asians. The administration of durvalumab after radical chemoradiotherapy has been shown to improve the outcome of locally advanced NSCLC; however, it cannot be used when grade 2 or higher radiation pneumonitis occurs. Therefore, it is extremely important to identify the predictive factors of grade 2 RP. The purpose of this study was to identify the factors that caused grade 2 RP and evaluate the impact of using VMAT on the incidence of grade 2 RP in Japanese population whose risk of RP is higher than other areas. MATERIALS/METHODS We retrospectively evaluated 124 patients who underwent radical radiotherapy for locally advanced NSCLC at our hospital from 2008 to 2019. RP was evaluated using the common terminology criteria for adverse events version 5.0. In order to analyze predictive factors of grade 2 RP, the mean lung dose and V5 Gy-V70 Gy were analyzed as the lung DVH parameters. The other predictive factors for grade 2 RP examined in this study were age, gender, performance status, vital capacity (VC), forced expiratory volume in one second (FEV1.0), lung volume, Brinkman index, presence of interstitial lung disease, presence of pulmonary emphysema, CRP, KL-6, tumor site (upper/middle vs lower lobe), planning target volume (PTV), total dose (≥ 70 Gy vs < 70 Gy). Fisher's exact test and logistic regression analysis was used to compare the incidence of grade 2 RP between the two groups for univariate analysis (UVA) and multivariate analysis (MVA), respectively. P values < 0.05 were considered statistically significant. Predictive performance of the predictor as a continuous variable was evaluated using the area under the receiver operator characteristic (ROC) curve (AUC). RESULTS Eighty-four patients underwent 3D-CRT (3D-CRT group), and 40 patients underwent VMAT (VMAT group). Of the 124 cases, grade 2 or higher RP was observed in 51 cases (41.1%). The incidence of grade 2 or higher RP was significantly lower in the VMAT group compared with 3D-CRT group (25.0% vs. 48.8%, P = 0.0185). As for predictive factors of grade 2 RP, all lung DVH parameters were related to grade 2 RP. Among these factors, V30 which had the highest AUC value (0.787) was used as a representative value of lung DVH, and examined together with the other prognostic factors of RP in MVA. Both the UVA and MVA showed that the treatment methods (3D-CRT, P = 0.0097 in MVA), tumor site (lower lobe, P = 0.0011 in MVA), total dose (≥ 70 Gy, P = 0.0008 in MVA), and V30Gy (≥ 19%, P < 0.0001 in MVA) were associated with grade 2 or higher RP. CONCLUSION We identified the predictive factors for grade 2 or higher RP in radiotherapy for locally advanced NSCLC patients. It was suggested that the use of VMAT could reduce the incidence of grade 2 RP.

The purpose of this study was to analyze the clinical results of concurrent chemoradiotherapy (CCRT) with volumetric modulated arc therapy (VMAT) for nasopharyngeal carcinoma (NPC) patients. Patients with stage II–IVB NPC who received CCRT with VMAT between 2010 and 2014 were included in this study. The planned dose was 70 Gy in 35 fractions. Twenty patients aged between 28 and 85 years (median 60 years) were assessed. With a median follow-up time of 47 months, the 3-year overall survival and progression-free survival rates were 85 and 65%, respectively. The 3-year local, regional and distant control rates were 78, 88 and 79%, respectively. At 0, 3, 6 and 12 months from CCRT, 19, 6, 3, and 1 patients had grade 2 dry mouth, respectively. No cases of grade 3 or worse dry mouth were observed. The severity of dry mouth was downgraded from grade 2 to grade 0 or 1 significantly earlier in younger patients (

The aim of the current planning study is to evaluate the ability of gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI)–guided stereotactic body radiation therapy (SBRT) planning by using intensity-modulated radiation therapy (IMRT) techniques in sparing the functional liver tissues during SBRT for hepatocellular carcinoma. In this study, 20 patients with hepatocellular carcinoma were enrolled. Functional liver tissues were defined according to quantitative liver-spleen contrast ratios ≥ 1.5 on a hepatobiliary phase scan. Functional images were fused with the planning computed tomography (CT) images; the following 2 SBRT plans were designed using a “step-and-shoot” static IMRT technique for each patient: (1) an anatomical SBRT plan optimization based on the total liver; and (2) a functional SBRT plan based on the functional liver. The total prescribed dose was 48 gray (Gy) in 4 fractions. Dosimetric parameters, including dose to 95% of the planning target volume (PTV D 95% ), percentages of total and functional liver volumes, which received doses from 5 to 30 Gy (V5 to V30 and fV5 to fV30), and mean doses to total and functional liver (MLD and fMLD, respectively) of the 2 plans were compared. Compared with anatomical plans, functional image-guided SBRT plans reduced MLD (mean: plan A, 5.5 Gy; and plan F, 5.1 Gy; p p

Background Bevacizumab improves symptoms via reducing the peritumoral edema and/or normalizing blood brain barrier, and occasionally via reducing the tumor size. However, the effect against active cystic components has not been documented yet. Materials and Methods Between 2008 and 2018, 139 patients with primary or metastatic brain tumors were treated with bevacizumab (BEV) in our institution. The images and symptoms before and after administration of BEV were examined, and changes in size of cysts were evaluated as follows: CR (complete disappearance), PR (reduction by ≥50%), MR (reduction by ≥25%), SD (size change, Patients with cyst showed significant improvement in symptoms after the treatment with bevacizumab (BEV) compared to patients without cyst. Bevacizumab is effective against progressively increasing cysts. Although cyst reduction effect and tumor response and/or overall survival are independent, BEV may be effective in patients who are symptomatic due to cystic enlargement.

Objective: The aim of the current study is to evaluate the effectiveness of reduction metal artifacts using kV-CT image with the single-energy based metal artefact reduction (SEMAR) technique by single-energy reconstruction, monochromatic CT and rED reconstructed by dual-energy reconstruction. Methods: Seven different metal materials (brass, aluminum, copper, stainless, steel, lead and titanium) were placed inside the water-based PMMA phantom. After DECT-based scan, the artefact index (AI) were evaluated with the kV-CT images with and without SEMAR by single-energy reconstruction, and raw-data based electron density (rED), monochromatic CT images by dual-energy reconstruction. Moreover, the AI with evaluated with rED and the converted ED images from the kV-CT and monochromatic CT images. Results: The minimum average value of the AI with all-metal inserts was approximately 80 keV. The AI without SEMAR was larger than that with SEMAR for the 80 kV and 135 kV CT images. In the comparison of the AI for the rED and ED images that were converted from 80 kV and 135 kV CT images with and without SEMAR, the monochromatic CT images of the PMMA phantom with inserted metal materials at 80 keV revealed that the kV-CT with SEMAR reduced the metal artefact substantially. Conclusion: The converted ED from the kV-CT and monochromatic CT images could be useful for a comparison of the AI using the same contrast scale. The kV-CT image with SEMAR by single-energy reconstruction was found to substantially reduce metal artefact. Advances in knowledge: The effectiveness of reduction of metal artifacts using single-energy based metal artefact reduction (SEMAR) technique and dual-energy CT (DECT) was evaluated the electron density conversion techniques.

The long-term outcomes of whole-breast and boost irradiation after breast-conserving surgery (BCS) for patients with breast cancer were retrospectively analyzed. Patients who received whole-breast and boost irradiation after BCS from 1990 to 2002 were included. Boost irradiation was administered to each tumor bed, regardless of the surgical margin status. The median doses of whole-breast and boost irradiation were 45 Gy in 25 fractions (range 36–45 Gy), and 14 Gy in 7 fractions (range 0–14 Gy), respectively. Data for 306 patients were analyzed. With a median follow-up time of 144 months, the 10-year overall survival, disease-free survival, ipsilateral breast tumor recurrence (IBTR), and metachronous contralateral breast cancer (MCBC) occurrence rates were 93.0, 84.1, 2.1, and 4.1 %, respectively. In the multivariate analysis, pT2 was a significant risk factor for IBTR (p = 0.041), while age ≤ 50 years and pT2 were significant risk factors for MCBC occurrence (p = 0.003 and 0.043, respectively). One patient (0.3 %) developed angiosarcoma in the irradiated region 120 months after the completion of radiation therapy. The 12-year outcome of breast-conserving therapy using whole-breast and boost irradiation with doses of 45 and 14 Gy, respectively, was favorable.