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.

Prognostic factors for esophageal squamous cell carcinoma without pathological lymph node metastasis after neoadjuvant therapy and surgery.

BACKGROUND: Pathological lymph node metastasis (LNM) following multimodal therapy is an important indicator of poor prognosis in patients with esophageal cancer. However, a significant number of patients without LNM are still at high risk for recurrence. METHODS: We assessed prognostic factors in 143 patients without pathological LNM who were diagnosed with locally advanced esophageal squamous cell carcinoma (ESCC) and underwent neoadjuvant chemotherapy (NAC) or chemoradiotherapy (NACRT), followed by surgery. RESULTS: Using univariate and multivariate analyses of recurrence-free survival, carcinoembryonic antigen (CEA) levels (hazard ratio [HR]: 2.17, 95% confidence interval [CI]: 1.12-4.23, and p = 0.02) and neutrophil-to-lymphocyte ratio (NLR) (HR: 1.22, 95% CI: 1.04-1.43, and p = 0.02) were significant independent covariates. Furthermore, pretherapeutic LNM (HR: 1.94, 95% CI: 1.003-3.76, and p = 0.049), NACRT (HR: 3.29, 95% CI: 1.30-8.33, and p = 0.01), poorly differentiated tumors (HR: 2.52, 95% CI: 1.28-4.98, and p = 0.01), and lymphovascular invasion (LVI) (HR: 2.78, 95% CI: 1.27-6.09, and p = 0.01) were also significant independent covariates. The recurrence rates among patients with 0/1, 2, 3, and 4/5 poor prognostic factors were significantly different (5.0%, 25.0%, 35.7%, and 53.8%, respectively; p = 0.001); the survival rates were stratified among these prognostic groups. CONCLUSIONS: Pretherapeutic CEA and NLR levels, pretherapeutic LNM, NACRT, poorly differentiated tumors, and LVI were significantly correlated with survivals in patients without pathological LNM after neoadjuvant therapy and surgery. Postoperative therapy should be considered in patients with ESCC with several indicators of recurrence, even in those without pathological LNM who underwent surgery following neoadjuvant therapy.

Long-term results of chemoradiotherapy with elective nodal irradiation for resectable locally advanced esophageal cancer in three-dimensional planning system.

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.

Influence of different air CT numbers for IVDT on the dose distribution in TomoTherapy MVCT.

This study aims to evaluate the effect of different air computed tomography (CT) numbers of the image value density table (IVDT) on the retrospective dose calculation of head-and-neck (HN) radiotherapy using TomoTherapy megavoltage CT (MVCT) images. The CT numbers of the inside and outside air and each tissue-equivalent plug of the "Cheese" phantom were obtained from TomoTherapy MVCT. Two IVDTs with different air CT numbers were created and applied to MVCT images of the HN anthropomorphic phantom and recalculated by Planned Adaptive to verify dose distribution. We defined the recalculation dose with MVCT images using both inside and outside air of the IVDT as IVDT MVCT inair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{inair}}$ and IVDT MVCT outair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{outair}}$ , respectively. Treatment planning doses calculated on kVCT images were compared with those calculated on MVCT images using two different IVDT tables, namely, IVDT MVCT inair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{inair}}$ and IVDT MVCT outair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{outair}}$ . The difference between average MVCT numbers ±1 standard deviation on inside and outside air of the calibration phantom was 65 ± 36 HU. This difference in MVCT number of air exceeded the recommendation lung tolerance for dose calculation error of 2%. The dose differences between the planning target volume (PTV): D98% , D50% , D2% and the organ at risk (OAR): Dmax , Dmean recalculated by IVDT MVCT inair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{inair}}$ and IVDT MVCT outair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{outair}}$ using MVCT images were a maximum of 0.7% and 1.2%, respectively. Recalculated doses to the PTV and OAR with MVCT showed that IVDT MVCT outair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{outair}}$ was 0.5%-0.7% closer to the kVCT treatment planning dose than IVDT MVCT inair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{inair}}$ . This study showed that IVDT MVCT outair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{outair}}$ was more accurate than IVDT MVCT inair ${\mathrm{IVDT}}_{\mathrm{MVCT}}^{\mathrm{inair}}$ in recalculating the dose HN cases of MVCT using TomoTherapy.

Xenopus laevis Oocyte Array Fluidic Device Integrated with Microelectrodes for A Compact Two-Electrode Voltage Clamping System.

We report on a compact two-electrode voltage clamping system composed of microfabricated electrodes and a fluidic device for Xenopus laevis oocytes. The device was fabricated by assembling Si-based electrode chips and acrylic frames to form fluidic channels. After the installation of Xenopus oocytes into the fluidic channels, the device can be separated in order to measure changes in oocyte plasma membrane potential in each channel using an external amplifier. Using fluid simulations and experiments, we investigated the success rates of Xenopus oocyte arrays and electrode insertion with respect to the flow rate. We successfully located each oocyte in the array and detected oocyte responses to chemical stimuli using our device.

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.

Robust optimization of VMAT for prostate cancer accounting for geometric uncertainty.

The aim of this study was to propose optimal robust planning by comparing the robustness with setup error with the robustness of a conventional planning target volume (PTV)-based plan and to compare the robust plan to the PTV-based plan for the target and organ at risk (OAR). Data from 13 patients with intermediate-to-high-risk localized prostate cancer who did not have T3b disease were analyzed. The dose distribution under multiple setup error scenarios was assessed using a conventional PTV-based plan. The clinical target volume (CTV) and OAR dose in moving coordinates were used for the dose constraint with the robust plan. The hybrid robust plan added the dose constraint of the PTV-rectum to the static coordinate system. When the isocenter was shifted by 10 mm in the superior-inferior direction and 8 mm in the right-left and anterior directions, the doses to the CTV, bladder, and rectum of the PTV-based plan, robust plan, and hybrid robust plan were compared. For the CTV D99% in the PTV-based plan and hybrid robust plan, over 95% of the prescribed dose was secured in all directions, except in the inferior direction. There was no significant difference between the PTV-based plan and the hybrid robust plan for rectum V70Gy , V60Gy , and V40Gy . This study proposed an optimization method for patients with prostate cancer. When the setup error occurred within the PTV margin, the dose robustness of the CTV for the hybrid robust plan was higher than that of the PTV-based plan, while maintaining the equivalent OAR dose.

Distribution of Lymph Node Metastasis in Esophageal Squamous Cell Carcinoma After Trimodal Therapy.

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.

Potential benefits of volumetric modulated arc therapy to reduce the incidence of ≥ grade 2 radiation pneumonitis in radiotherapy for locally advanced non-small cell lung cancer patients.

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.

Predictions of Pathological Features and Recurrence Based on FDG-PET Findings of Esophageal Squamous Cell Carcinoma after Trimodal Therapy.

BACKGROUND: The degree of metabolic activity in tumor cells can be determined by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET). Associations between FDG uptake by primary tumors of locally advanced esophageal squamous cell carcinoma (ESCC) under trimodal therapy and the pathological features of such tumors have not been fully investigated. PATIENTS AND METHODS: We evaluated relationships between the maximal standardized uptake (SUVmax) in primary tumors on preoperative PET images and pathological features as well as cancer recurrence in 143 patients with ESCC who underwent neoadjuvant chemoradiotherapy (NCRT) followed by surgery. RESULTS: The post-SUVmax significantly differed after NCRT for ypT and ypN status, lymphatic invasion (LI), venous invasion (VI), and recurrence. Furthermore, the %ΔSUVmax (rate of decrease between before and after NCRT) for LI, VI, and recurrence significantly differed. Univariate and multivariate analyses selected post-SUVmax and %ΔSUVmax as independent preoperative predictors of recurrence-free survival [hazard ratio (HR) 1.46; 95% confidence interval (CI) 1.24-1.72 and HR 0.97; 95% CI 0.96-0.99, respectively; p < 0.001 for both]. Recurrence-free and overall survival were significantly stratified according to optimal SUVmax cutoffs for predicting recurrence (post- and %ΔSUVmax: 2.8 and 70, respectively). CONCLUSIONS: The post- and %ΔSUVmax of primary tumors were significantly associated with the pathological features and recurrence of ESCC under trimodal therapy. Therefore, FDG-PET can preoperatively predict the degree of aggressive tumor behavior in ESCC under trimodal therapy.

A phase II study of adaptive two-step intensity-modulated radiation therapy (IMRT) with chemotherapy for loco-regionally advanced nasopharyngeal cancer (JCOG1015).

BACKGROUND: A phase II study of adaptive two-step intensity-modulated radiotherapy (IMRT) with chemotherapy for nasopharyngeal cancer (NPC) (JCOG1015) was conducted to evaluate the efficacy and safety. METHODS: Patients aged 20-75 years with stages II-IVB NPC were enrolled. As adaptive two-step IMRT, computed tomography planning was performed twice before IMRT for the initial plan of 46 Gy/23 fractions and during treatment for the boost plan of 24 Gy/12 fractions with a total dose of 70 Gy. Chemotherapy (cisplatin 80 mg/m2/3-weeks × 3 courses) was administered concurrently with IMRT, followed by adjuvant chemotherapy (cisplatin at 70 mg/m2 with 5-FU 700 at mg/m2 for 5 days/4 weeks × 3 courses). RESULTS: Between 2011 and 2014, 75 patients were enrolled from 12 institutions. The 3-year overall survival (OS) for the 75 patients was 88%, and the upper and lower limits of the 95% CI of 78%-94% were higher than the expected 3-year OS of 75% for the target population adjusted by the actual proportion of stage II:III:IV = 21%:44%:35%. The 3-year progression-free survival (PFS) and loco-regional PFS were 71% [59-80%] and 77% [66-85%], respectively. Although no grade 4-5 late toxicities were observed, 15 patients (20%) developed grade 3 late toxicities. Grade 2 xerostomia was noted in 26%, 12%, and 9% at 1, 2, and 3 years after starting IMRT, respectively. CONCLUSIONS: Adaptive two-step IMRT for NPC demonstrated an excellent 3-year OS with acceptable toxicities. This method may be one treatment option for locally advanced NPC.

Clinical Significance of 18F-Fluorodeoxyglucose-Positron Emission Tomography-Positive Lymph Nodes to Outcomes of Trimodal Therapy for Esophageal Squamous Cell Carcinoma.

BACKGROUND: The clinical significance of lymph node (LN) status determined by preoperative 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) has not been investigated in patients with locally advanced esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (NCRT) followed by surgery (trimodal therapy). METHODS: This study reviewed 132 consecutive patients with ESCC who had been preoperatively evaluated using FDG-PET before and after NCRT to analyze associations among LN status according to PET findings, pathologic LN metastasis, and prognosis of ESCC after trimodal therapy. RESULTS: Lymph nodes that were PET-positive both before and after NCRT comprised significant predictive markers of pathologic LN metastasis in station-by-station analyses (sensitivity, specificity, and accuracy respectively 41.7%, 95.0%, and 92.7% before, and 12.0%, 99.4%, and 95.6% after NCRT; both p < 0.0001). The numbers of LNs evaluated using PET before and after NCRT were significantly associated with those of pathologic metastatic LNs. Uni- and multivariable analyses selected LN status determined by PET before NCRT as a significant independent predictor of both recurrence-free [LN-negative vs LN-positive: hazard ratio (HR) 1.90; 95% confidence interval (CI) 1.02-3.23; p = 0.045] and overall survival (HR 2.62; 95% CI 1.29-5.30; p = 0.01). CONCLUSIONS: The status of LN determined by preoperative FDG-PET is significantly associated with pathologic LN status and the prognosis of ESCC with trimodal therapy. Thus, FDG-PET is a useful diagnostic tool for preoperative prediction of pathologic LN metastasis and survival among patients with ESCC.

HTLV-1 Tax-Specific CTL Epitope-Pulsed Dendritic Cell Therapy Reduces Proviral Load in Infected Rats with Immune Tolerance against Tax.

Adult T cell leukemia/lymphoma (ATL), a CD4+ T cell malignancy with a poor prognosis, is caused by human T cell leukemia virus type 1 (HTLV-1) infection. High proviral load (PVL) is a risk factor for the progression to ATL. We previously reported that some asymptomatic carriers had severely reduced functions of CTLs against HTLV-1 Tax, the major target Ag. Furthermore, the CTL responses tended to be inversely correlated with PVL, suggesting that weak HTLV-1-specific CTL responses may be involved in the elevation of PVL. Our previous animal studies indicated that oral HTLV-1 infection, the major route of infection, caused persistent infection with higher PVL in rats compared with other routes. In this study, we found that Tax-specific CD8+ T cells were present, but not functional, in orally infected rats as observed in some human asymptomatic carriers. Even in the infected rats with immune unresponsiveness against Tax, Tax-specific CTL epitope-pulsed dendritic cell (DC) therapy reduced the PVL and induced Tax-specific CD8+ T cells capable of proliferating and producing IFN-γ. Furthermore, we found that monocyte-derived DCs from most infected individuals still had the capacity to stimulate CMV-specific autologous CTLs in vitro, indicating that DC therapy may be applicable to most infected individuals. These data suggest that peptide-pulsed DC immunotherapy will be useful to induce functional HTLV-1-specific CTLs and decrease PVL in infected individuals with high PVL and impaired HTLV-1-specific CTL responses, thereby reducing the risk of the development of ATL.

Photon and electron backscatter dose and energy spectrum analysis around Lipiodol using flattened and unflattened beams.

PURPOSE: The aim of the current study was to evaluate the backscatter dose and energy spectrum from the Lipiodol with flattening filter (FF) and flattening filter-free (FFF) beams. Moreover, the backscatter range, that was defined as the backscatter distance (BD) are revealed. METHODS: 6 MVX FF and FFF beams were delivered by TrueBeam. Two dose calculation methods with Monte Carlo calculation were used with a virtual phantom in which the Lipiodol (3 × 3 × 3 cm3 ) was located at a depth of 5.0 cm in a water-equivalent phantom (20 × 20 × 20 cm3 ). The first dose calculation was an analysis of the dose and energy spectrum with the complete scattering of photons and electrons, and the other was a specified dose analysis only with scattering from a specified region. The specified dose analysis was divided into a scattering of primary photons and a scattering of electrons. RESULTS: The lower-energy photons contributed to the backscatter, while the high-energy photons contributed the difference of the backscatter dose between the FF and FFF beams. Although the difference in the dose from the scattered electrons between the FF and FFF beams was within 1%, the difference of the dose from the scattered photons between the FF and FFF beams was 5.4% at a depth of 4.98 cm. CONCLUSIONS: The backscatter range from the Lipiodol was within 3 mm and depended on the Compton scatter from the primary photons. The backscatter dose from the Lipiodol can be useful in clinical applications in cases where the backscatter region is located within a tumor.

Evaluation of raw-data-based and calculated electron density for contrast media with a dual-energy CT technique.

OBJECTIVES: The aim of the current study is to evaluate the accuracy and the precision of raw-data-based relative electron density (REDraw) and the calibration-based RED (REDcal) at a range of low-RED to high-RED for tissue-equivalent phantom materials by comparing them with reference RED (REDref) and to present the difference of REDraw and REDcal for the contrast medium using dual-energy CT (DECT). METHODS: The REDraw images were reconstructed by raw-data-based decomposition using DECT. For evaluation of the accuracy of the REDraw, REDref was calculated for the tissue-equivalent phantom materials based on their specified density and elemental composition. The REDcal images were calculated using three models: Lung-Bone model, Lung-Ti model and Lung-Ti (SEMAR) model which used single-energy metal artifact reduction (SEMAR). The difference between REDraw and REDcal was calculated. RESULTS: In the titanium rod core, the deviations of REDraw and REDcal (Lung-Bone model, Lung-Ti model and Lung-Ti model with SEMAR) from REDref were 0.45%, 50.8%, 15.4% and 15.0%, respectively. The largest differences between REDraw and REDcal (Lung-Bone model, Lung-Ti model and Lung-Ti model with SEMAR) in the contrast medium phantom were 8.2%, -23.7%, and 28.7%, respectively. However, the differences between REDraw and REDcal values were within 10% at 20 mg/ml. The standard deviation of the REDraw was significantly smaller than the REDcal with three models in the titanium and the materials that had low CT numbers. CONCLUSION: The REDcal values could be affected by beam hardening artifacts and the REDcal was less accurate than REDraw for high-Z materials as titanium. ADVANCES IN KNOWLEDGE: The raw-data-based reconstruction method could reduce the beam hardening artifact compared with image-based reconstruction and increase the accuracy for the RED estimation in high-Z materials, such as titanium and iodinated contrast medium.

Long-term outcome of stereotactic body radiotherapy for patients with small hepatocellular carcinoma.

AIM: To evaluate the long-term outcome of stereotactic body radiotherapy in patients with small hepatocellular carcinoma who were ineligible for resection or ablation therapies. METHODS: A total of 65 patients with 74 hepatocellular carcinomas (median tumor size 16 mm) were enrolled in the present study. They were treated with the prescribed dose of 48 Gy in four fractions at the isocenter. We extended the observation period and analyzed long-term outcomes, including overall survival, progression-free survival, local control, and various prognostic factors, in these patients. RESULTS: The median follow-up period was 41 months for all patients and 62 months for surviving patients. The 3- and 5-year overall survival rates were 56.3% (95% confidence interval, 44.1-68.5%) and 41.4% (95% confidence interval, 28.7-54.1%), respectively. The 3- and 5-year progression-free survival rates were 25.4% (95% confidence interval, 14.0-36.8%) and 10.6% (95% confidence interval, 1.5-19.8%), respectively. The 3- and 5-year local control rates were both 100% (95% confidence interval 100%). Liver toxicities exceeding grade 3 were observed in 15 patients (23.1%). The proportion of patients who had grade ≥3 toxicities did not increase. Adverse effects (grade ≤2) presented as significant prognostic factors of overall survival, while TNM stage (T1N0M0) was a significant prognostic factor of progression-free survival after multivariate analysis. CONCLUSIONS: Stereotactic body radiotherapy was effective for patients with small hepatocellular carcinomas who were ineligible for resection or ablation therapies. The incidence of grade ≥3 adverse effects did not increase, even after longer follow-up times.

Evaluation of Prognostic Factors for Esophageal Squamous Cell Carcinoma Treated with Neoadjuvant Chemoradiotherapy Followed by Surgery.

BACKGROUND: Intensive trimodality therapy is needed for locally advanced esophageal squamous cell carcinoma (ESCC). However, some patients develop recurrence and die of cancer even after trimodality therapy. METHODS: We evaluated prognostic factors based on data from 125 patients with ESCC who underwent neoadjuvant chemoradiotherapy (NCRT) comprising concurrent chemotherapy and 40 Gy of radiation, followed by curative-intent esophagectomy. RESULTS: Thirty-four (27.2%) patients achieved a pathological complete response (pCR) after NCRT. The 5-year recurrence-free (RFS) and overall survival (OS) rates of all patients were 49.2 and 52.9%, respectively, and were significantly better for patients with pCR than without pCR (p = 0.01 and 0.02, respectively). Univariate and multivariate analyses selected performance status [PS 0 vs. 1: hazard ratio (HR) 2.05; 95% confidence interval (CI) 1.30-4.84; p = 0.01] and ypN (0 vs. 1: HR 2.33; 95% CI 1.12-4.84; p = 0.02; 0 vs. 2/3: HR 3.73; 95% CI 1.68-8.28; p = 0.001) as independent covariates for RFS. Furthermore, PS (0 vs. 1; HR 2.94; 95% CI 1.51-5.72; p = 0.002) and ypN (0 vs. 1; HR 2.26; 95% CI 1.09-4.69; p = 0.03; 0 vs. 2/3: HR 3.90; 95% CI 1.79-8.48; p = 0.001) were also independent covariates for OS. CONCLUSIONS: Performance status 1 and ypN+ were significantly associated with a poor prognosis after trimodality therapy for ESCC.

Effect of secondary electron generation on dose enhancement in Lipiodol with and without a flattening filter.

PURPOSE: Lipiodol, which was used in transcatheter arterial chemoembolization before liver stereotactic body radiation therapy (SBRT), remains in SBRT. Previous we reported the dose enhancement in Lipiodol using 10 MV (10×) FFF beam. In this study, we compared the dose enhancement in Lipiodol and evaluated the probability of electron generation (PEG) for the dose enhancement using flattening filter (FF) and flattening filter free (FFF) beams. METHODS: FF and FFF for 6 MV (6×) and 10× beams were delivered by TrueBeam. The dose enhancement factor (DEF), energy spectrum, and PEG was calculated using Monte Carlo (MC) code BEAMnrc and heavy ion transport code system (PHITS). RESULTS: DEFs for FF and FFF 6× beams were 7.0% and 17.0% at the center of Lipiodol (depth, 6.5 cm). DEFs for FF and FFF 10× beams were 8.2% and 10.5% at the center of Lipiodol. Spectral analysis revealed that the FFF beams contained more low-energy (0-0.3 MeV) electrons than the FF beams, and the FF beams contained more high-energy (>0.3 MeV) electrons than the FFF beams in Lipiodol. The difference between FFF and FF beam DEFs was larger for 6× than for 10×. This occurred because the 10× beams contained more high-energy electrons. The PEGs for photoelectric absorption and Compton scattering for the FFF beams were higher than those for the FF beams. The PEG for the photoelectric absorption was higher than that for Compton scattering. CONCLUSIONS: FFF beam contained more low-energy photons and it contributed to the dose enhancement. Energy spectra and PEGs are useful for analyzing the mechanisms of dose enhancement.

[Study of Dose Recalculation Method on Overriding Lung Density Using CBCT Image in the Thorax].

It is a useful method for the adaptive radiotherapy (ART) to calculate absorbed dose accurately on the image set taken by on-board cone beam computed tomography (CBCT) attached to linac for image-guided radiation therapy (IGRT). For this purpose, a simple and accurate calculation method is necessary. Several papers report that it is possible to calculate easily and accurately by using several methods of researches in the neck and prostate, but the lung density varies greatly depending on patient thorax condition. In this study, we propose a new dose recalculation method, which is a simple procedure and can achieve accurate dose calculation considered different lung densities in each patient. By using this method, it is possible to calculate exclusive of artifacts in CBCT because of overriding the lung density. The dose error between dose recalculation of the CBCT image and treatment plan agreed within±1%. Therefore, this method is expected to be a useful method for accurate dose calculation with CBCT image for ART.

Energy spectrum and dose enhancement due to the depth of the Lipiodol position using flattened and unflattened beams.

AIM: Lipiodol was used for stereotactic body radiotherapy combining trans arterial chemoembolization. Lipiodol used for tumour seeking in trans arterial chemoembolization remains in stereotactic body radiation therapy. In our previous study, we reported the dose enhancement effect in Lipiodol with 10× flattening-filter-free (FFF). The objective of our study was to evaluate the dose enhancement and energy spectrum of photons and electrons due to the Lipiodol depth with flattened (FF) and FFF beams. METHODS: FF and FFF for 6 MV beams from TrueBeam were used in this study. The Lipiodol (3 × 3 × 3 cm3) was located at depths of 1, 3, 5, 10, 20, and 30 cm in water. The dose enhancement factor (DEF) and the energy fluence were obtained by Monte Carlo calculations of the particle and heavy ion transport code system (PHITS). RESULTS: The DEFs at the centre of Lipiodol with the FF beam were 6.8, 7.3, 7.6, 7.2, 6.1, and 5.7% and those with the FFF beam were 20.6, 22.0, 21.9, 20.0, 12.3, and 12.1% at depths of 1, 3, 5, 10, 20, and 30 cm, respectively, where Lipiodol was located in water. Moreover, spectrum results showed that more low-energy photons and electrons were present at shallow depth where Lipiodol was located in water. The variation in the low-energy spectrum due to the depth of the Lipiodol position was more explicit with the FFF beam than that with the FF beam. CONCLUSIONS: The current study revealed variations in the DEF and energy spectrum due to the depth of the Lipiodol position with the FF and FFF beams. Although the FF beam could reduce the effect of energy dependence due to the depth of the Lipiodol position, the dose enhancement was overall small. To cause a large dose enhancement, the FFF beam with the distance of the patient surface to Lipiodol within 10 cm should be used.