Dosiomics for intensity-modulated radiotherapy in patients with prostate cancer: survival analysis stratified by baseline prostate-specific antigen and Gleason grade group in a 2-institutional retrospective study.

OBJECTIVE: This study evaluated the prognostic impact of the quality of dose distribution using dosiomics in patients with prostate cancer, stratified by pretreatment prostate-specific antigen (PSA) levels and Gleason grade (GG) group. METHODS: A total of 721 patients (Japanese Foundation for Cancer Research [JFCR] cohort: N = 489 and Tokyo Radiation Oncology Clinic [TROC] cohort: N = 232) with localized prostate cancer treated by intensity-modulated radiation therapy were enrolled. Two predictive dosiomic features for biochemical recurrence (BCR) were selected and patients were divided into certain groups stratified by pretreatment PSA levels and GG. Freedom from biochemical failure (FFBF) was estimated using the Kaplan-Meier method based on each dosiomic feature and univariate discrimination was evaluated using the log-rank test. As an exploratory analysis, a dosiomics hazard (DH) score was developed and its prognostic power for BCR was examined. RESULTS: The dosiomic feature extracted from planning target volume (PTV) significantly distinguished the high- and low-risk groups in patients with PSA levels >10 ng/mL (7-year FFBF: 86.7% vs 76.1%, P < .01), GG 4 (92.2% vs 76.9%, P < .01), and GG 5 (83.1% vs 77.8%, P = .04). The DH score showed significant association with BCR (hazard score: 2.04; 95% confidence interval: 1.38-3.01; P < .001). CONCLUSION: The quality of planned dose distribution on PTV may affect the prognosis of patients with poor prognostic factors, such as PSA levels >10 ng/mL and higher GGs. ADVANCES IN KNOWLEDGE: The effects of planned dose distribution on prognosis differ depending on the patient's clinical background.

Radiomics and dosiomics for predicting complete response to definitive chemoradiotherapy patients with oesophageal squamous cell cancer using the hybrid institution model.

OBJECTIVES: To develop a multi-institutional prediction model to estimate the local response to oesophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy based on radiomics and dosiomics features. METHODS: The local responses were categorised into two groups (incomplete and complete). An external validation model and a hybrid model that the patients from two institutions were mixed randomly were proposed. The ESCC patients at stages I-IV who underwent chemoradiotherapy from 2012 to 2017 and had follow-up duration of more than 5 years were included. The patients who received palliative or pre-operable radiotherapy and had no FDG PET images were excluded. The segmentations included the GTV, CTV, and PTV which are used in treatment planning. In addition, shrinkage, expansion, and shell regions were created. Radiomic and dosiomic features were extracted from CT, FDG PET images, and dose distribution. Machine learning-based prediction models were developed using decision tree, support vector machine, k-nearest neighbour (kNN) algorithm, and neural network (NN) classifiers. RESULTS: A total of 116 and 26 patients enrolled at Centre 1 and Centre 2, respectively. The external validation model exhibited the highest accuracy with 65.4% for CT-based radiomics, 77.9% for PET-based radiomics, and 72.1% for dosiomics based on the NN classifiers. The hybrid model exhibited the highest accuracy of 84.4% for CT-based radiomics based on the kNN classifier, 86.0% for PET-based radiomics, and 79.0% for dosiomics based on the NN classifiers. CONCLUSION: The proposed hybrid model exhibited promising predictive performance for the local response to definitive radiotherapy in ESCC patients. CLINICAL RELEVANCE STATEMENT: The prediction of the complete response for oesophageal cancer patients may contribute to improving overall survival. The hybrid model has the potential to improve prediction performance than the external validation model that was conventionally proposed. KEY POINTS: • Radiomics and dosiomics used to predict response in patients with oesophageal cancer receiving definitive radiotherapy. • Hybrid model with neural network classifier of PET-based radiomics improved prediction accuracy by 8.1%. • The hybrid model has the potential to improve prediction performance.

Unbiased evaluation of predicted gamma passing rate by an event-mixing technique.

BACKGROUND: Predicting models of the gamma passing rate (GPR) have been studied to substitute the measurement-based gamma analysis. Since these studies used data from different radiotherapy systems comprising TPS, linear accelerator, and detector array, it has been difficult to compare the performances of the predicting models among institutions with different radiotherapy systems. PURPOSE: We aimed to develop unbiased scoring methods to evaluate the performance of the models predicting the GPR, by introducing both best and worst limits for the performance of the GPR prediction. METHODS: Two hundred head-and-neck VMAT plans were used to develop a framework. The GPRs were measured using the ArcCHECK device. The predicted GPR [p] was generated using a deep learning-based model [pDL ]. The predicting model was evaluated using four metrics: standard deviation (SD) [σ], Pearson's correlation coefficient (CC) [r], mean squared error (MSE) [s], and mean absolute error (MAE) [a]. The best limit [ σ m ${\sigma _m}$ , r m ${r_m}$ , s m ${s_m}$ , and a m ${a_m}$ ] was estimated by measuring the SD of measured GPR [m] by shifting the device along the longitudinal direction to measure different sampling points. Mimicked best and worst p's [pbest and pworst ] were generated from pDL . The worst limit was defined such that m and p have no correlation [CC ∼ 0]. The worst limit [σMix , rMix , sMix , and aMix ] was generated using the event-mixing (EM) technique originally introduced in high-energy physics experiments. The range of σ, r, s, and a was defined to be [ σ m , σ Mix ] $[ {{\sigma _m},{\sigma _{{\mathrm{Mix}}}}} ]$ , [ 0 , r m ] $[ {0,{r_m}} ]$ , [ s m , s Mix ] $[ {{s_m},{s_{{\mathrm{Mix}}}}} ]$ , and [ a m , a Mix ] $[ {{a_m},{a_{{\mathrm{Mix}}}}} ]$ . The achievement score (AS) independently based on σ, r, s, and a were calculated for pDL , pbest and pworst . The probability that p fails the gamma analysis (alert frequency; AF) was estimated as a function of σ d ${\sigma _d}$ values within the [ σ m ${\sigma _m}$ , σMix ] range for the 3%/2 mm data with a 95% criterion. RESULTS: SDs of the best limit were well reproduced by σ m = 0.531 100 - m ${\sigma _m} = \;0.531\sqrt {100 - m} $ . The EM technique successfully generated the ( m , p ) $( {m,p} )$ pairs with no correlation. The AS using four metrics showed good agreement. This agreement indicates successful definitions of both best and worst limits, consistent definitions of the AS, and successful generations of mixed events. The AF for the DL-based model with the 3%/2 mm tolerance was 31.5% and 63.0% with CL's 99% and 99.9%, respectively. CONCLUSION: We developed the AS to evaluate the predicting model of the GPR in an unbiased manner by excluding the effects of the precision of the radiotherapy system and the spreading of the GPR. The best and worst limits of the GPR prediction were successfully generated using the measured precision of the GPR and the EM technique, respectively. The AS and σ p ${\sigma _p}$ are expected to enable objective evaluation of the predicting model and setting exact achievement goal of precision for the predicted GPR.

[Analysis of Preventive Cases Using Resilience Engineering in Radiotherapy Department].

PURPOSE: Resilience engineering is the ability of a system to adjust its own functions and maintain the required behavior in the face of changes and disturbances, and resilience potential is a necessary requirement. We aimed to clarify the relationship between resilience potential and error prevention cases. METHOD: Based on the error cases reported in our department, we aggregated the relationship with resilience potential for each radiation treatment process. RESULT: As a result of tabulating the relationship, we were able to recognize and prevent errors by taking preventive measures from past cases. On the other hand, in cases that slipped through the check mechanism, errors were discovered because of a sense of discomfort in unusual situations, and some error cases could be prevented by increasing the resilience potential. CONCLUSION: This study found that preparation, observation, coping, and utilization of past experiences are related to resilience potential in preventive cases.

CT number calibration audit in photon radiation therapy.

BACKGROUND: Inadequate computed tomography (CT) number calibration curves affect dose calculation accuracy. Although CT number calibration curves registered in treatment planning systems (TPSs) should be consistent with human tissues, it is unclear whether adequate CT number calibration is performed because CT number calibration curves have not been assessed for various types of CT number calibration phantoms and TPSs. PURPOSE: The purpose of this study was to investigate CT number calibration curves for mass density (ρ) and relative electron density (ρe ). METHODS: A CT number calibration audit phantom was sent to 24 Japanese photon therapy institutes from the evaluating institute and scanned using their individual clinical CT scan protocols. The CT images of the audit phantom and institute-specific CT number calibration curves were submitted to the evaluating institute for analyzing the calibration curves registered in the TPSs at the participating institutes. The institute-specific CT number calibration curves were created using commercial phantom (Gammex, Gammex Inc., Middleton, WI, USA) or CIRS phantom (Computerized Imaging Reference Systems, Inc., Norfolk, VA, USA)). At the evaluating institute, theoretical CT number calibration curves were created using a stoichiometric CT number calibration method based on the CT image, and the institute-specific CT number calibration curves were compared with the theoretical calibration curve. Differences in ρ and ρe over the multiple points on the curve (Δρm and Δρe,m , respectively) were calculated for each CT number, categorized for each phantom vendor and TPS, and evaluated for three tissue types: lung, soft tissues, and bones. In particular, the CT-ρ calibration curves for Tomotherapy TPSs (ACCURAY, Sunnyvale, CA, USA) were categorized separately from the Gammex CT-ρ calibration curves because the available tissue-equivalent materials (TEMs) were limited by the manufacturer recommendations. In addition, the differences in ρ and ρe for the specific TEMs (ΔρTEM and Δρe,TEM , respectively) were calculated by subtracting the ρ or ρe of the TEMs from the theoretical CT-ρ or CT-ρe calibration curve. RESULTS: The mean ± standard deviation (SD) of Δρm and Δρe,m for the Gammex phantom were -1.1 ± 1.2 g/cm3 and -0.2 ± 1.1, -0.3 ± 0.9 g/cm3 and 0.8 ± 1.3, and -0.9 ± 1.3 g/cm3 and 1.0 ± 1.5 for lung, soft tissues, and bones, respectively. The mean ± SD of Δρm and Δρe,m for the CIRS phantom were 0.3 ± 0.8 g/cm3 and 0.9 ± 0.9, 0.6 ± 0.6 g/cm3 and 1.4 ± 0.8, and 0.2 ± 0.5 g/cm3 and 1.6 ± 0.5 for lung, soft tissues, and bones, respectively. The mean ± SD of Δρm for Tomotherapy TPSs was 2.1 ± 1.4 g/cm3 for soft tissues, which is larger than those for other TPSs. The mean ± SD of Δρe,TEM for the Gammex brain phantom (BRN-SR2) was -1.8 ± 0.4, implying that the tissue equivalency of the BRN-SR2 plug was slightly inferior to that of other plugs. CONCLUSIONS: Latent deviations between human tissues and TEMs were found by comparing the CT number calibration curves of the various institutes.

[Development of a Phantom and Analysis Program for Assessment of Positional Accuracy of Image-guided Radiation Therapy].

PURPOSE: We created a phantom and analysis program for the assessment of IGRT positional accuracy. We verified the accuracy of analysis and the practicality of this evaluation method at several facilities. METHOD: End-to-end test was performed using an in-house phantom, and EPID images were acquired after displacement by an arbitrary amount using a micrometer, with after image registration as the reference. The difference between the center of the target and the irradiated field was calculated using our in-house analysis program and commercial software. The end-to-end test was conducted at three facilities, and the IGRT positional accuracy evaluation was verified. RESULT: The maximum difference between the displacement of the target determined from the EPID image and the arbitrary amount of micrometer displacement was 0.24 mm for the in-house analysis program and 0.30 mm for the commercial software. The maximum difference between the center of the target and the irradiation field on EPID images acquired at the three facilities was 0.97 mm. CONCLUSION: The proposed evaluation method using our in-house phantom and analysis program can be used for the assessment of IGRT positional accuracy.

Radio Frequency Identification Gate System to Identify Misused Personal Dosimeters.

The use of two personal dosimeters, one worn over and one worn under a protective apron, provides the best estimate of effective dose. However, inappropriate positioning of dosimeters is a common occurrence, resulting in abnormally high or low radiation exposure records. Although such incorrect positioning can be identified by radiation exposure records, doing so is time-consuming and labor-intensive for administrators. Therefore, a system that can identify incorrect locations of dosimeters without burdening administrators must be developed. In this study, we developed a radio frequency identification (RFID) gate system that can differentiate between two RFID-tagged dosimeters placed over and under a metal apron and identify misused dosimeters. To simulate the position of the RFID-tagged dosimeters, we designed four dosimeter-wearing classes, including "proper use" and three types of "misuse" (i.e., "reversed," "both under," and "both over"). When the system predicts "misuse" based on the tag reading, the worker is alerted with lights and alarms. The system performance was evaluated using a confusion matrix, with an overall accuracy of 97.75%, demonstrating high classification performance. The safety of the system against life support devices was also investigated, demonstrating that they were not affected by the electric field at 0.3 m or more from the antenna of the system under any transmit powers tested. This RFID gate system is highly capable of identifying incorrectly positioned dosimeters, enabling real-time monitoring of dosimeters to manage their positioning.

The impact of the COVID-19 pandemic on radiotherapy delivery in Japan: An observational study based on the national database.

BACKGROUND: This study analyzed the impact of the coronavirus disease 2019 (COVID-19) pandemic on radiotherapy delivery in Japan using a high-quality Japanese national database based on universal health coverage. METHODS: We performed a retrospective observational study using National Database of Health Insurance Claims and Specific Health Checkups of Japan open data focused on radiotherapy between fiscal year (FY) 2019 and FY2020 and the number of COVID-19 cases from the Ministry of Health, Labour, and Welfare. We statistically analyzed the relationship between the number of COVID-19 cases and the number of radiotherapy deliveries in Japan as a whole and by prefecture. RESULTS: The total number of external beam radiotherapy (EBRT) fractions was 4,472,140 in FY2019 and 4,227,673 in FY2020 (-5.8%). EBRT courses were 250,395 in FY2019 and 240,329 in FY2020 (-4.0%), stereotactic radiotherapy courses were 27,619 in FY2019 and 31,786 in FY2020 (+15.1%), and single-fraction palliative radiotherapy courses were 4124 in FY2019 and 5255 in FY2020 (+21.5%). The total number of breast and prostate hypofractionated radiotherapy (HFRT) fractions was 155,773 and 48,188 in FY2019, and 200,256 and 84,230 in FY2020 (+28.6% and +74.8%), respectively. In the Pearson correlation analysis, EBRT fractions were lower, and breast HFRT fractions were higher in prefectures with more COVID-19 cases. CONCLUSIONS: Overall, radiotherapy delivery in Japan was relatively stable after the pandemic, with an increase in HFRT. Also, EBRT fractions decreased, and breast HFRT were more likely to be used in prefectures with more COVID-19 cases.

Biological dosimetric impact of dose-delivery time for hypoxic tumour with modified microdosimetric kinetic model.

Background: An improved microdosimetric kinetic model (MKM) can address radiobiological effects with prolonged delivery times. However, these do not consider the effects of oxygen. The current study aimed to evaluate the biological dosimetric effects associated with the dose delivery time in hypoxic tumours with improved MKM for photon radiation therapy. Materials and methods: Cell survival was measured under anoxic, hypoxic, and oxic conditions using the Monte Carlo code PHITS. The effect of the dose rate of 0.5-24 Gy/min for the biological dose (Dbio) was estimated using the microdosimetric kinetic model. The dose per fraction and pressure of O2 (pO2) in the tumour varied from 2 to 20 Gy and from 0.01 to 5.0% pO2, respectively. Results: The ratio of the Dbio at 1.0-24 Gy/min to that at 0.5 Gy/min (RDR) was higher at higher doses. The maximum RDR was 1.09 at 1.0 Gy/min, 1.12 at 12 Gy/min, and 1.13 at 24 Gy/min. The ratio of the Dbio at 0.01-2.0% of pO2 to that at 5.0% of pO2 (Roxy) was within 0.1 for 2-20 Gy of physical dose. The maximum Roxy was 0.42 at 0.01% pO2, 0.76 at 0.4% pO2, 0.89 at 1% pO2, and 0.96 at 2% pO2. Conclusion: Our proposed model can estimate the cell killing and biological dose under hypoxia in a clinical and realistic patient. A shorter dose-delivery time with a higher oxygen distribution increased the radiobiological effect. It was more effective at higher doses per fraction than at lower doses.

Novel simulation for dosimetry impact of diaphragm respiratory motion in four-dimensional volumetric modulated arc therapy for esophageal cancer.

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 ΔD100% and ΔDmean 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 ΔD1cc and ΔD2cc 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.

Dose uncertainty due to energy dependence in dual-energy computed tomography.

Purpose: To evaluate the absolute dose uncertainty at 2 different energies and for the large and small bowtie filters in dual-energy computed tomography (DECT). Material and methods: Measurements were performed using DECT at 80 kV and 140 kilovoltage peak (kVp), and single-energy computed tomography (CT) at 120 kV. The absolute dose was calculated from the mass-energy absorption obtained from the half-value layer (HVL) of aluminium. Results: The difference in the water-to-air ratio of the mean mass energy-absorption coefficients at 80 kV and 140 kV was 2.0% for the small bow-tie filter and 3.0% for the large bow-tie filter. At lower tube voltages, the difference in the absorbed dose with the large and small bow-tie filters was larger. Conclusions: The absolute dose uncertainty due to energy dependence was 3.0%, which could be reduced with single-energy beams at 120 kV or by using the average effective energy measurement with dual-energy beams.

Long-Term Follow-up of a Randomized Controlled Trial on Accelerated Radiation Therapy Versus Standard Fractionated Radiation Therapy for Early Glottic Cancer (JCOG0701A3).

PURPOSE: We previously reported the primary results of JCOG0701, a randomized, multicenter, phase 3, noninferiority trial comparing accelerated fractionation (Ax) to standard fractionation (SF) for early glottic cancer. In the primary results, although the similar efficacy of 3-year progression-free survival and toxicity of Ax compared with SF was observed, the noninferiority of Ax was not confirmed statistically. To evaluate the long-term follow-up results of JCOG0701, we conducted JCOG0701A3 as an ancillary study of JCOG0701. METHODS AND MATERIALS: In JCOG0701, 370 patients were randomly assigned to receive SF of 66 to 70 Gy (33-35 fractions; n = 184) or Ax of 60 to 64.8 Gy (25-27 fractions; n = 186). The data cutoff date for this analysis was in June 2020. Overall survival, progression-free survival, and late adverse events including central nervous system ischemia were analyzed. RESULTS: With a median follow-up period of 7.1 years (range, 0.1-12.4), progression-free survival of the SF and Ax arms were 76.2% and 78.2% at 5 years and 72.7% and 74.8% at 7 years (P = .44). OS of the SF and Ax arms were 92.7% and 89.6% at 5 years and 90.8% and 86.5% at 7 years (P = .92). Among 366 patients with a protocol treatment, the cumulative incidence of late adverse events of the SF and Ax arms were 11.9% and 7.4% at 8 years (hazard ratio, 0.53; 95% CI, 0.28-1.01; P = .06). Central nervous system ischemia of grade 2 or higher was observed in 4.1% for the SF arm and 1.1% for the Ax arm (P = .098). CONCLUSIONS: After long-term follow-up, Ax showed comparable efficacy to SF and a tendency for better safety. Ax may be suitable for early glottic cancer because of its convenience in minimizing treatment time, cost, and labor.

Effect of Target Changes on Target Coverage and Dose to the Normal Brain in Fractionated Stereotactic Radiation Therapy for Metastatic Brain Tumors.

Purpose: We evaluated the dosimetric effect of tumor changes in patients with fractionated brain stereotactic radiation therapy (SRT) on the tumor and normal brain using repeat verification magnetic resonance imaging (MRI) in the middle of the treatment period. Methods and Materials: Fifteen large intracranial metastatic lesions with fractionated SRT were scanned employing standardized planning MRI (MRI-1). Repeat verification MRI (MRI-2) were performed during the middle of the irradiation period. Gross tumor volume (GTV) was defined as the volume of the contrast-enhancing lesion on T1-weighted MRI with gadolinium contrast agent. The doses to the tumor and normal brain were evaluated on the MRI-1 scan. Beam configuration and intensity on the initial volumetric modulated arc therapy plan were used to evaluate the dose to the tumor and the normal brain on MRI-2. We evaluated the effect of D98% (percent dose irradiating 98% of the volume) on the GTV using the plans on the MRI-1 and MRI-2 scans. For the normal brain, the V90%, V80%, and V50% (volume of the normal brain receiving >90%, 80%, and 50% of the prescribed dose, respectively) were investigated. Results: Three (20% of the total) and 4 (26% of the total) tumors exhibited volume shrinkage or enlargement changes of >10%. Five (33% of the total) tumors exhibited volume shrinkage and enlargement changes of <10%. Three tumors (20% of the total) showed no volume changes. D98% of the GTV increased in patients with tumor shrinkage because of dose inhomogeneity and decreased in patients with tumor enlargement, with a coefficient of determination of 0.28. The V90%, V80%, and V50% increase with decreasing tumor volumes and were linearly related to the tumor volume difference with a coefficient of determination values of 0.97, 0.98, and 0.97, respectively. Conclusions: Repeat verification MRI for brain fractionated SRT during the treatment period should be considered to reduce the magnitude of target underdosing or normal brain overdosing.

Interfractional Liver Positional Motion Under Exhaled Breath Holding Based on Cone Beam Computed Tomography.

BACKGROUND/AIM: We measured interfractional liver positional motion in liver stereotactic body radiotherapy (SBRT) with exhaled breath holding (BH) based on kilovoltage (kV) cone-beam computed tomography (CBCT) images. PATIENTS AND METHODS: We collected 528 pre-treatment kV-CBCT images from 132 patients who underwent liver SBRT under exhaled BH using the Abches system, a non-electronic contact-based respiratory monitoring device, and analyzed them to investigate interfractional liver positional motion. Planning computed tomography (CT) scans were obtained using the Abches system when the patients were under exhaled BH. Translational 3-degree-of-freedom (DOF) soft-tissue-based image registration was performed using the kV-CBCT images under exhaled BH after 6-DOF vertebral bone image registration. Interfractional liver positional motions in the left-right (LR), anteroposterior (AP), and craniocaudal (CC) directions were defined based on the differences in the position of the liver relative to the vertebral bones. RESULTS: For all fractions, the absolute mean±standard deviation for the interfractional liver positional motion in the LR, AP, and CC directions was 0.7±1.0 mm, 1.0±1.5 mm, and 2.8±3.1 mm, respectively. The liver interfractional systematic/random positional motions in the LR, AP, and CC directions were 0.9/1.2 mm, 1.4/1.8 mm, and 2.9/3.9 mm, respectively. For all fractions, 100.0%, 98.3%, and 86.9% of the interfractional liver positional motions in the LR, AP, and CC directions, respectively, were less than 5 mm. CONCLUSION: CBCT-guided online correction should be used to correct interfractional liver positions errors present in liver SBRT with exhaled BH.

Multicenter retrospective study of stereotactic body radiotherapy for patients with previously untreated initial small hepatocellular carcinoma.

AIM: We aimed to verify the therapeutic efficacy and safety of stereotactic body radiotherapy (SBRT) for previously untreated initial small hepatocellular carcinoma (HCC) in a multicenter, retrospective study. METHODS: Patients who underwent SBRT for HCC at the Japanese Society of Clinical Oncology (JCOG) member hospitals in Japan between July 2013 and December 2017 and met the following eligibility criteria were included: (1) initial HCC; (2) ≤3 nodules, ≤5 cm in diameter; (3) Child-Pugh score of A or B; and (4) unsuitability for or refusal of standard treatment. We analyzed the overall survival, recurrence-free survival, and cumulative incidence of local recurrence rate, and adverse events directly related to SBRT. RESULTS: Seventy-three patients with 79 lesions from 14 hospitals were analyzed. The median age was 77 years (range: 50-89 years), and the median tumor size was 23 mm (range: 6-50 mm). The median radiation dose was 40 Gy (range: 35-60 Gy) in five fractions (range: 4-8). The median follow-up period was 45 months (range: 0-103 months). The 3-year overall survival, recurrence-free survival, and cumulative incidence of local recurrence rates were 69.9% (95% CI: 58.7%-81%), 57.9% (95% CI: 45.2%-70.5%), and 20.0% (95% CI: 11.2%-30.5%), respectively. Four cases (5.5%) of adverse events of grade 3 or higher were reported: three cases of grade 3 and one case of grade 4 (duodenal ulcer). No grade 5 toxicities were observed. CONCLUSION: SBRT is a promising treatment modality, particularly for small HCCs, as they are not suitable for standard treatment.

Endoscopic findings suggestive of a high risk of non-radical cure after definitive chemoradiotherapy for cT1bN0M0 esophageal squamous cell carcinoma.

BACKGROUND: Definitive chemoradiotherapy (DCRT) is a curative treatment option for cT1bN0M0 esophageal squamous cell carcinoma (ESCC); however, local residual disease and recurrence after complete remission may occur. We aimed to identify endoscopic findings associated with the risk of non-radical cure (local remnant or recurrence) after DCRT for cT1bN0M0 ESCC. METHODS: We retrospectively analyzed 40 consecutive patients with cT1bN0M0 ESCC who had undergone DCRT between January 2007 and December 2017. We examined the endoscopic findings in patients with residual or recurrent (RR) disease (RR group) and those without RR disease [non-RR (NRR) group] after DCRT. We also evaluated outcomes after DCRT for each endoscopic finding. RESULTS: There were 10 patients in the RR group and 30 patients in the NRR group. The RR group had a significantly larger tumor size and a higher proportion of lesions with type 0-I. The 5-year relapse-free survival rate was significantly lower in type 0-I and in the presence of B3 vessels. Endoscopic findings in 15 patients with cT1bN0M0 ESCC, type 0-I, who underwent DCRT revealed significantly more reddish lesions in the RR group compared to the NRR group. CONCLUSIONS: cT1bN0M0 ESCC large size, with B3 vessels, and type 0-I has a high risk of non-radical cure after DCRT, especially the reddish type 0-I, which may need to be considered for treatment similar to advanced cancer, including surgery with preoperative DCRT.

Characterization of scanning orientation and lateral response artifact for EBT4 Gafchromic film.

The purpose of this study was to investigate the impact of scanning orientation and lateral response artifact (LRA) effects on the dose-response of EBT4 films and compare it with that of EBT3 films. Dose-response curves for EBT3 and EBT4 films in red-green-blue (RGB) color channels in portrait orientation were created for unexposed films and for films exposed to doses ranging from 0 to 1 000 cGy. Portrait and landscape orientations of the EBT3 and EBT4 films were scanned to investigate the scanning orientation effect in the red channel. EBT3 and EBT4 films were irradiated to assess the LRA in the red channel using a field size of 15 × 15 cm2 and delivered doses of 200, 400, and 600 cGy. Films were scanned at the edge of the scanner bed, and the measured doses were compared with the treatment planning system (TPS) calculated doses at a position 100 mm lateral to the scanner center. At a dose of 200 cGy, the differences in optical density (OD) in the red, green, and blue color channels between EBT3 and EBT4 films were 0.035 (24.8%), 0.042 (49.7%), and 0.022 (64.4%), respectively. The EBT4 film slightly improved the scanning orientation compared to the EBT3 film. The OD difference in the different scanning orientations for the EBT3 and EBT4 films was 0.015 (6.8%) and 0.007 (3.9%), respectively, at a dose of 200 cGy. This is equivalent to a 20 or 10 cGy variation at a dose of 200 cGy. Compared with the TPS calculation, the measurement doses for EBT3 and EBT4 films irradiated at 200 cGy were approximately 16% and 13% higher, respectively, at the 100 mm off-centered position. The EBT4 film showed an improvement concerning the impact of LRA compared with the EBT3 film. This study demonstrated that the response of EBT4 film to a dose in the blue channel was less sensitive and showed an improvement in the scanning orientation and LRA effects.

Effectiveness of Spacers in Brachytherapy With 198Au Grains for Patients With Buccal Mucosa Cancer.

BACKGROUND/AIM: The aim of this study was to investigate the use of spacers and their efficacy in brachytherapy with 198Au grains for buccal mucosa cancer. PATIENTS AND METHODS: Sixteen patients with squamous cell carcinoma of the buccal mucosa who were treated with 198Au grain brachytherapy were included. The distance between 198Au grains, distance between 198Au 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 198Au grains without and with a spacer was 7.4 and 10.7 mm, respectively; this was significantly different. The median distance between 198Au 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 198Au 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 198Au grains, and between 198Au grains and the jawbone. In buccal mucosa cancer, using a spacer in brachytherapy with 198Au grains appears to reduce jawbone complications.

Prognostic Value of Radiomics Analysis of Skeletal Muscle After Radical Irradiation of Esophageal Cancer.

BACKGROUND/AIM: Sarcopenia is an independent survival predictor in several tumor types. Computed tomography (CT) is the standard measurement for body composition assessment. Radiomics analysis of CT images allows for the precise evaluation of skeletal muscles. This study aimed to construct a prognostic survival model for patients with esophageal cancer who underwent radical irradiation using skeletal muscle radiomics. PATIENTS AND METHODS: We retrospectively identified patients with esophageal cancer who underwent radical irradiation at our institution between April 2008 and December 2017. Skeletal muscle radiomics were extracted from an axial pretreatment CT at the third lumbar vertebral level. The prediction model was constructed using machine learning coupled with the least absolute shrinkage and selection operator (LASSO). The predictive nomogram model comprised clinical factors with radiomic features. Three prediction models were created: clinical, radiomics, and combined. RESULTS: Ninety-eight patients with 98 esophageal cancers were enrolled in this study. The median observation period was 57.5 months (range=1-98 months). Thirty-five radiomics features were selected by LASSO analysis, and a prediction model was constructed using training and validation data. The average of the accuracy, specificity, sensitivity, and area under the concentration-time curve for predicting survival in esophageal cancer in the combined model were 75%, 92%, and 0.86, respectively. The C-indices of the clinical, radiomics, and combined models were 0.76, 0.80, and 0.88, respectively. CONCLUSION: A prediction model with skeletal muscle radiomics and clinical data might help determine survival outcomes in patients with esophageal cancer treated with radical radiotherapy.

Image masking using convolutional networks improves performance classification of radiation pneumonitis for non-small cell lung cancer.

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.