Nicaraven attenuates the acquired radioresistance of established tumors in mouse models via PARP inhibition.

Nicaraven has been reported to inhibit the activity of poly (ADP-ribose) polymerase (PARP). In this study, we investigated the probable ability of nicaraven to attenuate cancer radioresistance during fractionated radiotherapy. Tumor models were established in C57BL/6 mice and BALB/c nude mice by subcutaneous injection of Lewis mouse lung carcinoma cancer cells and A549 human lung cancer cells, respectively. When the tumors had grown to approximately 100 mm3, we initiated fractionated radiotherapy. Nicaraven or saline was administered immediately after each irradiation exposure. Compared to saline treatment, nicaraven administration significantly induced gamma-H2AX foci formation and cell apoptosis in tumors at 1 or 3 days after an additional challenge exposure to 10 Gy and inhibited tumor growth during the short-term follow-up period, suggesting increased radiosensitivity of cancer cells. Moreover, the expression of PARP in tumor tissue was decreased by nicaraven administration. Our data suggest that nicaraven likely attenuates the acquired radioresistance of cancers through PARP inhibition.

Clinical impact of multimodal treatment including chemoradiotherapy, conversion surgery and postoperative chemotherapy for borderline resectable and unresectable locally advanced pancreatic cancer without disease progression after gemcitabine plus nab-paclitaxel.

BACKGROUND: The purpose of this study was to investigate treatment outcomes of chemoradiotherapy (CRT) using S-1 with or without conversion surgery after gemcitabine plus nab-paclitaxel (GnP) for borderline resectable (BR) and unresectable locally advanced (UR-LA) pancreatic cancer. METHODS: From 2016 to 2020, patients without disease progression after GnP for BR or UR-LA pancreatic cancer underwent CRT with S-1. If distant metastasis was not detected after CRT, conversion surgery and oral administration of S-1 as postoperative adjuvant chemotherapy for at least 6 months was performed. RESULTS: Forty patients were included in the present study. The median number of cycles of GnP was 6. Surgery was performed after CRT in 25 patients. The median progression-free survival (PFS) and overall survival (OS) periods from the start of radiotherapy were 24.6 and 27.4 months, respectively. The OS periods from the start of radiotherapy in patients who underwent conversion surgery and those who did not undergo conversion surgery were 41.3 and 16.8 months, respectively. The PFS periods from the start of radiotherapy in patients who underwent surgery and those who did not undergo surgery were 28.3 and 8.6 months, respectively. Patients who were able to receive S-1 after conversion surgery for more than 6 months had better OS than those who were not (p = 0.039), although there was no significant difference of PFS (p = 0.365). CONCLUSIONS: In BR/UR-LA pancreatic cancer without disease progression after GnP, multimodal treatment including CRT, conversion surgery and the scheduled postoperative chemotherapy may be effective.

Development and validation of an [18F]FDG-PET/CT radiomic model for predicting progression-free survival for patients with stage II - III thoracic esophageal squamous cell carcinoma who are treated with definitive chemoradiotherapy.

BACKGROUND: Radiomics is a method for extracting a large amount of information from images and used to predict treatment outcomes, side effects and diagnosis. In this study, we developed and validated a radiomic model of [18F]FDG-PET/CT for predicting progression-free survival (PFS) of definitive chemoradiotherapy (dCRT) for patients with esophageal cancer. MATERIAL AND METHODS: Patients with stage II - III esophageal cancer who underwent [18F]FDG-PET/CT within 45 days before dCRT between 2005 and 2017 were included. Patients were randomly assigned to a training set (85 patients) and a validation set (45 patients). Radiomic parameters inside the area of standard uptake value ≥ 3 were calculated. The open-source software 3D slicer and Pyradiomics were used for segmentation and calculating radiomic parameters, respectively. Eight hundred sixty radiomic parameters and general information were investigated.In the training set, a radiomic model for PFS was made from the LASSO Cox regression model and Rad-score was calculated. In the validation set, the model was applied to Kaplan-Meier curves. The median value of Rad-score in the training set was used as a cutoff value in the validation set. JMP was used for statistical analysis. RStudio was used for the LASSO Cox regression model. p < 0.05 was defined as significant. RESULTS: The median follow-up periods were 21.9 months for all patients and 63.4 months for survivors. The 5-year PFS rate was 24.0%. In the training set, the LASSO Cox regression model selects 6 parameters and made a model. The low Rad-score group had significantly better PFS than that the high Rad-score group (p = 0.019). In the validation set, the low Rad-score group had significantly better PFS than that the high Rad-score group (p = 0.040). CONCLUSIONS: The [18F]FDG-PET/CT radiomic model could predict PFS for patients with esophageal cancer who received dCRT.

Definitive radiotherapy consisting of external beam radiotherapy without central shielding and 3D image-guided brachytherapy for patients with cervical cancer: feasibility for Japanese patients and dose-response analyses for local control in the low-dose range.

OBJECTIVE: To assess the feasibility of external beam radiotherapy without central shielding in definitive radiotherapy for Japanese patients with cervical cancer. METHODS: We retrospectively analysed the data of cervical cancer patients treated with definitive radiotherapy consisting of external beam radiotherapy without central shielding and three-dimensional-image-guided brachytherapy. RESULTS: The study included 167 patients (T1 + 2 = 108, T3 + 4 = 59) from eight Japanese institutions. For three-dimensional-image-guided brachytherapy, intra-cavitary and interstitial brachytherapy was utilized in 33 patients (20%). The median follow-up was 26.6 months (interquartile range, 20-43.2). The maximum rectal D2 (75 Gy)/bladder D2 (90 Gy) constraints were deviated by 6%/10% and 10%/5% for T1 + 2 and T3 + 4, respectively. The 2-year incidence of ≥grade 3 proctitis/cystitis was 4%/1% for T1 + 2 and 10%/2% for T3 + 4. The 2-year local progression-free survival was 89% for T1 + 2 and 82% for T3 + 4. For T1 + 2, the 2-year local progression-free survival for the high-risk clinical target volume D90 ≥ 68 Gy (indicated by receiver operating characteristic analysis; area under the curve = 0.711) was 92% versus 67% for <68 Gy (log-rank; P = 0.019). Cox multivariate analysis indicated that the high-risk clinical target volume D90 was one of independent predictors of local failure (P = 0.0006). For T3 + 4, the 2-year local progression-free survival was 87% for the high-risk clinical target volume <82 cm3 (area under the curve = 0.67) and 43% for ≥82 cm3 (P = 0.0004). Only the high-risk clinical target volume was an independent predictor of local failure (P = 0.0024). CONCLUSIONS: Definitive radiotherapy consisting of external beam radiotherapy without central shielding and three-dimensional-image-guided brachytherapy was feasible for Japanese patients with cervical cancer. Dose de-escalation from the current global standards is suggested for patients with T1 + 2 disease.

Evaluation of the MVCT-based radiomic features as prognostic factor in patients with head and neck squamous cell carcinoma.

BACKGROUND: Megavoltage computed tomography (MVCT) images acquired during each radiotherapy session may be useful for delta radiomics. However, no studies have examined whether the MVCT-based radiomics has prognostic power. Therefore, the purpose of this study was to examine the prognostic power of the MVCT-based radiomics for head and neck squamous cell carcinoma (HNSCC) patients. METHODS: 100 HNSCC patients who received definitive radiotherapy were analyzed and divided into two groups: training (n = 70) and test (n = 30) sets. MVCT images obtained using TomoTherapy for the first fraction of radiotherapy and planning kilovoltage CT (kVCT) images obtained using Aquilion LB CT scanner were analyzed. Primary gross tumor volume (GTV) was propagated from kVCT to MVCT images using rigid registration, and 107 radiomic features were extracted from the GTV in MVCT and kVCT images. Least absolute shrinkage and selection operator (LASSO) Cox regression model was used to examine the association between overall survival (OS) and rad score calculated for each patient by weighting the feature value through the coefficient when features were selected. Then, the predictive values of MVCT-based and kVCT-based rad score and patient-, treatment-, and tumor-specific factors were evaluated. RESULTS: C-indices of the rad score for MVCT- and kVCT-based radiomics were 0.667 and 0.685, respectively. The C-indices of 6 clinical factors were 0.538-0.622. The 3-year OS was significantly different between high- and low-risk groups according to the MVCT-based rad score (50% vs. 83%; p < 0.01). CONCLUSIONS: Our results suggested that MVCT-based radiomics had stronger prognostic power than any single clinical factor and was a useful prognostic factor when predicting OS in HNSCC patients.

Impact of CT scan parameters on deformable image registration accuracy using deformable thorax phantom.

The purpose of this study was to evaluate the deformable image registration (DIR) accuracy using various CT scan parameters with deformable thorax phantom. Our developed deformable thorax phantom (Dephan, Chiyoda Technol Corp, Tokyo, Japan) was used. The phantom consists of a base phantom, an inner phantom, and a motor-derived piston. The base phantom is an acrylic cylinder phantom with a diameter of 180 mm, which simulates the chest wall. The inner phantom consists of deformable, 20 mm thick disk-shaped sponges with 48 Lucite beads and 48 nylon cross-wires which simulate the vascular and bronchial bifurcations of the lung. Peak-exhale and peak-inhale images of the deformable phantom were acquired using a CT scanner (Aquilion LB, TOSHIBA). To evaluate the impact of CT scan parameters on DIR accuracy, we used the four tube voltages (80, 100, 120, and 135 kV) and six reconstruction algorithms (FC11, FC13, FC15, FC41, FC44, and FC52). Intensity-based DIR was performed between the two images using MIM Maestro (MIM software, Cleveland, USA). Fiducial markers (beads and cross-wires) based target registration error (TRE) was used for quantitative evaluation of DIR. In case with different tube voltages, the range of average TRE were 4.44-5.69 mm (reconstruction algorithm: FC13). In case with different reconstruction algorithms, the range of average TRE were 4.26-4.59 mm (tube voltage: 120 kV). The TRE were differed by up to 3.0 mm (3.96-6.96 mm) depending on the combination of tube voltage and reconstruction algorithm. Our result indicated that CT scan parameters had moderate impact of TRE, especially for reconstruction algorithms for the deformable thorax phantom.

Dosimetric impact of deformable image registration using radiophotoluminescent glass dosimeters with a physical geometric phantom.

PURPOSE: To study the dosimetry impact of deformable image registration (DIR) using radiophotoluminescent glass dosimeter (RPLD) and custom developed phantom with various inserts. METHODS: The phantom was developed to facilitate simultaneous evaluation of geometric and dosimetric accuracy of DIR. Four computed tomography (CT) images of the phantom were acquired with four different configurations. Four volumetric modulated arc therapy (VMAT) plans were computed for different phantom. Two different patterns were applied to combination of four phantom configurations. RPLD dose measurement was combined between corresponding two phantom configurations. DIR-based dose accumulation was calculated between corresponding two CT images with two commercial DIR software and various DIR parameter settings, and an open source software. Accumulated dose calculated using DIR was then compared with measured dose using RPLD. RESULTS: The mean ± standard deviation (SD) of dose difference was 2.71 ± 0.23% (range, 2.22%-3.01%) for tumor-proxy and 3.74 ± 0.79% (range, 1.56%-4.83%) for rectum-proxy. The mean ± SD of target registration error (TRE) was 1.66 ± 1.36 mm (range, 0.03-4.43 mm) for tumor-proxy and 6.87 ± 5.49 mm (range, 0.54-17.47 mm) for rectum-proxy. These results suggested that DIR accuracy had wide range among DIR parameter setting. CONCLUSIONS: The dose difference observed in our study was 3% for tumor-proxy and within 5% for rectum-proxy. The custom developed physical phantom with inserts showed potential for accurate evaluation of DIR-based dose accumulation. The prospect of simultaneous evaluation of geometric and dosimetric DIR accuracy in a single phantom may be useful for validation of DIR for clinical use.

Improvement of deep learning prediction model in patient-specific QA for VMAT with MLC leaf position map and patient's dose distribution.

PURPOSE: Deep learning-based virtual patient-specific quality assurance (QA) is a novel technique that enables patient QA without measurement. However, this method could be improved by further evaluating the optimal data to be used as input. Therefore, a deep learning-based model that uses multileaf collimator (MLC) information per control point and dose distribution in patient's CT as inputs was developed. METHODS: Overall, 96 volumetric-modulated arc therapy plans generated for prostate cancer treatment were used. We developed a model (Model 1) that can predict measurement-based gamma passing rate (GPR) for a treatment plan using data stored as a map reflecting the MLC leaf position at each control point (MLPM) and data of the dose distribution in patient's CT as inputs. The evaluation of the model was based on the mean absolute error (MAE) and Pearson's correlation coefficient (r) between the measured and predicted GPR. For comparison, we also analyzed models trained with the dose distribution in patient's CT alone (Model 2) and with dose distributions recalculated on a virtual phantom CT (Model 3). RESULTS: At the 2%/2 mm criterion, MAE[%] and r for Model 1, Model 2, and Model 3 were 2.32% ± 0.43% and 0.54 ± 0.03, 2.70% ± 0.26%, and 0.32 ± 0.08, and 2.96% ± 0.23% and 0.24 ± 0.22, respectively; at the 3%/3 mm criterion, these values were 1.25% ± 0.05% and 0.36 ± 0.18, 1.57% ± 0.35% and 0.19 ± 0.20, and 1.39% ± 0.32% and 0.17 ± 0.22, respectively. This result showed that Model 1 exhibited the lowest MAE and highest r at both criteria of 2%/2 mm and 3%3 mm. CONCLUSIONS: These findings showed that a model that combines the MLPM and dose distribution in patient's CT exhibited a better GPR prediction performance compared with the other two studied models.

Evaluation of Unity 1.5 T MR-linac plan quality in patients with prostate cancer.

The Unity magnetic resonance (MR) linear accelerator (MRL) with MR-guided adaptive radiotherapy (MRgART) is capable of online MRgART where images are acquired on the treatment day and the radiation treatment plan is immediately replanned and performed. We evaluated the MRgART plan quality and plan reproducibility of the Unity MRL in patients with prostate cancer. There were five low- or moderate-risk and five high-risk patients who received 36.25 Gy or 40 Gy, respectively in five fractions. All patients underwent simulation magnetic resonance imaging (MRI) and five online adaptive MRI. We created plans for 5, 7, 9, 16, and 20 beams and for 60, 100, and 150 segments. We evaluated the target and organ doses for different number of beams and segments, respectively. Variation in dose constraint between the simulation plan and online adaptive plan was measured for each patient to assess plan reproducibility. The plan quality improved with the increasing number of beams. However, the proportion of significantly improved dose constraints decreased as the number of beams increased. For some dose parameters, there were statistically significant differences between 60 and 100 segments, and 100 and 150 segments. The plan of five beams exhibited limited reproducibility. The number of segments had minimal impact on plan reproducibility, but 60 segments sometimes failed to meet dose constraints for online adaptive plan. The optimization and delivery time increased with the number of beams and segments. We do not recommend using five or fewer beams for a reproducible and high-quality plan in the Unity MRL. In addition, many number of segments and beams may help meet dose constraints during online adaptive plan. Treatment with the Unity MRL should be performed with the appropriate number of beams and segments to achieve a good balance among plan quality, delivery time, and optimization time.

Survival prediction nomogram for patients with vertebral bone metastases treated with palliative radiotherapy.

Background: In the treatment of vertebral bone metastases, estimating patient prognosis is important to select the optimal treatment strategy. The purpose of this study was to identify prognostic factors for vertebral bone metastases treated with palliative radiotherapy and to establish a nomogram for predicting patient survival. Materials and methods: We analyzed patients who underwent palliative radiotherapy for vertebral bone metastasis between January 2010 and December 2020 at a single institution. Exclusion criteria were as follows: (1) primary bone malignancy, (2) stereotactic body radiotherapy, (3) concurrent radiotherapy to sites other than the vertebral bone, (4) radiotherapy to other sites within 12 weeks before or after the current radiotherapy, and (5) lack of more than half of blood test data before radiotherapy. Results: A total of 487 patients met the inclusion criteria. Clinical and hematologic data were collected from the patient record system. Patients were divided into training and test groups in a 7:3 ratio. Multivariate Cox regression analysis in the training cohort revealed six significant factors, including a history of chemotherapy, primary site (breast cancer, prostate cancer, or hematologic malignancy), use of analgesics, neutrophil-lymphocyte ratio, serum albumin, and lactate dehydrogenase. A prognostic nomogram was developed and validated in the test cohort. The area under the curve (AUC) values in predicting survival at 6, 24, and 60 months were 0.83, 0.88, and 0.88 in the training cohort and 0.85, 0.81, and 0.79 in the test cohort, respectively. Conclusions: This nomogram may help to select the treatment strategy for vertebral bone metastases.

PP6 deficiency in mice with KRAS mutation and Trp53 loss promotes early death by PDAC with cachexia-like features.

To examine effects of PP6 gene (Ppp6c) deficiency on pancreatic tumor development, we developed pancreas-specific, tamoxifen-inducible Cre-mediated KP (KRAS(G12D) plus Trp53-deficient) mice (cKP mice) and crossed them with Ppp6cflox / flox mice. cKP mice with the homozygous Ppp6c deletion developed pancreatic tumors, became emaciated and required euthanasia within 150 days of mutation induction, phenotypes that were not seen in heterozygous or wild-type (WT) mice. At 30 days, a comparative analysis of genes commonly altered in homozygous versus WT Ppp6c cKP mice revealed enhanced activation of Erk and NFκB pathways in homozygotes. By 80 days, the number and size of tumors and number of precancerous lesions had significantly increased in the pancreas of Ppp6c homozygous relative to heterozygous or WT cKP mice. Ppp6c-/- tumors were pathologically diagnosed as pancreatic ductal adenocarcinoma (PDAC) undergoing the epithelial-mesenchymal transition (EMT), and cancer cells had invaded surrounding tissues in three out of six cases. Transcriptome and metabolome analyses indicated an enhanced cancer-specific glycolytic metabolism in Ppp6c-deficient cKP mice and the increased expression of inflammatory cytokines. Individual Ppp6c-/- cKP mice showed weight loss, decreased skeletal muscle and adipose tissue, and increased circulating tumor necrosis factor (TNF)-α and IL-6 levels, suggestive of systemic inflammation. Overall, Ppp6c deficiency in the presence of K-ras mutations and Trp53 gene deficiency promoted pancreatic tumorigenesis with generalized cachexia and early death. This study provided the first evidence that Ppp6c suppresses mouse pancreatic carcinogenesis and supports the use of Ppp6c-deficient cKP mice as a model for developing treatments for cachexia associated with pancreatic cancer.

Durvalumab after chemoradiotherapy for locally advanced non-small cell lung cancer prolonged distant metastasis-free survival, progression-free survival and overall survival in clinical practice.

BACKGROUND: In clinical practice, the effect of durvalumab and radiation pneumonitis (RP) on survival after intensity-modulated radiotherapy (IMRT) is not fully understood. The purpose of this retrospective study was to investigate factors related to distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) after IMRT for locally advanced non-small cell lung cancer (LA-NSCLC). METHODS: All patients who were treated with conventional fractionated IMRT for LA-NSCLC between April 2016 and March 2021 were eligible. Time-to-event data were assessed by using the Kaplan-Meier estimator, and the Cox proportional hazards model was used for prognostic factor analyses. Factors that emerged after the start of IMRT, such as durvalumab administration or the development of RP, were analysed as time-dependent covariates. RESULTS: A total of 68 consecutive patients treated with conventional fractionated IMRT for LA-NSCLC were analysed. Sixty-six patients completed radiotherapy, 50 patients received concurrent chemotherapy, and 36 patients received adjuvant durvalumab. During the median follow-up period of 14.3 months, 23 patients died, and tumour progression occurred in 37 patients, including 28 patients with distant metastases. The 1-year DMFS rate, PFS rate and OS rate were 59.9%, 48.7% and 84.2%, respectively. Grade 2 RP occurred in 16 patients, grade 3 in 6 patients and grade 5 in 1 patient. The 1-year cumulative incidences of grade 2 or higher RP and grade 3 or higher RP were 33.8% and 10.3%, respectively. The results of multivariate analyses showed that durvalumab had a significantly lower hazard ratio (HR) for DMFS, PFS and OS (HR 0.31, p < 0.01; HR 0.33, p < 0.01 and HR 0.32, p = 0.02), respectively. Grade 2 or higher RP showed significance for DMFS and a nonsignificant trend for OS (HR 2.28, p = 0.04 and HR 2.12, p = 0.13), respectively, whereas a higher percentage of lung volume receiving 20 Gy or higher was significant for PFS (HR 2.25, p = 0.01). CONCLUSIONS: In clinical practice, durvalumab administration following IMRT with concomitant chemotherapy showed a significant survival benefit. Reducing the risk of grade 2 or higher RP would also be beneficial.

Palliative radiotherapy for gastric cancer bleeding: a multi-institutional retrospective study.

BACKGROUND: Palliative radiotherapy for gastric cancer bleeding has been reported to be a safe and effective treatment, but predictive factors for achievement of hemostasis and overall survival have not been established. METHODS: In this retrospective study, 120 courses of palliative radiotherapy for gastric cancer bleeding in 117 patients in 4 institutes in Japan were reviewed with approval of the ethical committee in each institute. The rate of achieving hemostasis was evaluated by 50% or more reduction of red blood cell transfusion before and after the start of radiotherapy, elevation of blood hemoglobin concentration in a period of 4 weeks from the start of radiotherapy or improvement of subjective or objective clinical symptoms in a period of 4 weeks from the start of radiotherapy. Predictive factors for overall survival and achieving hemostasis were investigated with the Cox hazards model. RESULTS: The median overall survival period was 3.7 months. Multivariate analysis showed that absence of metastatic disease, higher biological effective dose, higher serum albumin level, lower blood urea nitrogen level and lower neutrophil-to-lymphocyte ratio (NLR) were associated with longer overall survival. Elevation of hemoglobin concentration in a period of 4 weeks from the start of radiotherapy (mean concentration: 8.2 g/dL vs. 8.9 g/dL, p = 0.006) and decrease in the amount of red cell transfusion from a 4-week period before to a 4-week period after the start of radiotherapy (mean amount: 716 mL vs. 230 mL, p < 0.0001) were observed. The overall rate of achievement of hemostasis was 59.6%. In multivariate analysis, higher biological effective dose was associated with achievement of hemostasis. Grade 2 or higher acute adverse effects related to radiotherapy were observed in 17.5% of cases in 120 treatment courses. Six cases (5.0%) had grade 3 or 4 adverse effects including gastric penetration in 1 patient and anorexia requiring total parental nutrition in 3 patients. No grade 5 adverse effects were observed. CONCLUSIONS: Palliative radiotherapy for gastric cancer bleeding seems to be an effective and safe treatment strategy. Higher treatment dose was associated with longer overall survival and a hemostatic effect. Some hematological parameters may predict overall survival, and they would be helpful for deciding the treatment strategy.

Patterns of failure after salvage chemoradiotherapy for postoperative loco-regional recurrent esophageal cancer: 20-year experience in a single institution in Japan.

PURPOSE: The purpose of the present study was to evaluate patterns of recurrence after salvage chemoradiotherapy (SCRT) for postoperative loco-regional recurrent esophageal cancer. METHODS: We reviewed records for 114 patients with postoperative loco-regional recurrent esophageal cancer treated by platinum-based chemoradiotherapy between 2000 and 2020, and we evaluated the patterns of failure in patients who had recurrence again or who had been observed for 2 years or more after SCRT at the last observation date. RESULTS: One hundred and three patients were enrolled in this study. The median observation period for survivors was 60 months. Fifty-three patients died of esophageal cancer and nine patients died of other diseases. The 5-year overall survival rate, cause-specific survival rate and disease-control rate were 43.7%, 45.3% and 37.0%, respectively. Sixty-five patients had failure after SCRT. In those patients, 26 patients had only distant organ or non-regional lymph node metastases, 26 patients had only loco-regional failure, and 13 patients had both. Of those 65 patients, 64 patients showed failure within 42 months after SCRT. Of 39 patients with loco-regional failure, failure in the irradiated field was observed in 28 patients. Of those 28 patients, 27 patients showed failure within 24 months and the other patient showed failure at 26.5 months. CONCLUSIONS: The patterns of failure after SCRT for patients with postoperative loco-regional recurrent esophageal cancer were shown. The patterns of failure suggest that follow-up for at least 4 years after SCRT should be performed for those patients.

The benefit of concurrent chemotherapy with radiotherapy for esophageal cancer is limited in Asian patients aged 80 years or older: a SEER database analysis.

PURPOSE: To evaluate the benefit of concurrent chemotherapy with radiotherapy (RT) for esophageal cancer in Asian patients aged ≥ 80 years using the Surveillance, Epidemiology, and End Results (SEER) database. MATERIALS AND METHODS: Among more than 7000 patients with squamous cell carcinoma or adenocarcinoma who were treated by RT without surgery for esophageal cancer in the SEER database, 2047 patients aged ≥ 80 years were analyzed. Patients who received chemoradiotherapy (CRT group) and patients who received RT alone (RT alone group) were matched with a propensity score. RESULTS: The median observation period for survivors was 57 months. The 3-year and 5-year overall survival rates in all patients were 15.2% and 8.5%, respectively. The 3-year and 5-year cause-specific survival rates in all patients were 20.8% and 14.5%, respectively. After propensity score matching, the overall survival rate in the CRT group was significantly higher than that in the RT alone group (5-year overall survival rates: 11.9% and 3.2%, respectively, p < 0.001). In 108 Asian or Pacific Islander patients, there was no significant difference (5-year overall survival rates: 13.5% and 0%, respectively, p = 0.291), although the overall survival rate in the CRT group was significantly higher than that in the RT alone group in any other race. CONCLUSIONS: It is controversial whether CRT is beneficial for Asian or Pacific Islander patients aged 80 years or older with esophageal cancer based on Analysis of data in SEER database.

Clinical outcomes and prognostic factors for esophageal cancer in patients aged 80 years or older who were treated with definitive radiotherapy and chemoradiotherapy.

OBJECTIVE: Aging of populations has been rapidly increasing worldwide. The aim of this study was to identify prognostic factors of overall survival (OS) and progression-free survival (PFS) in patients aged 80 years or older who had esophageal cancer and received radiotherapy. METHODS: Patients aged 80 years or older who received radiotherapy between 2004 and 2015 were retrospectively reviewed. Pretreatment age, gender, performance status, Charlson comorbidity index score, tumor location, histology, clinical stage, results of blood tests and treatment methods were obtained to determine prognostic factors of OS and PFS. Survival curves were drawn using the Kaplan-Meier method and prognostic factors were analyzed using Cox's hazards model. RESULTS: Ninety-two patients were included. Thirty-five patients were treated with chemo-radiotherapy. The median follow-up period was 19.0 months. The 3-year OS and PFS rates were 44.7% and 28.4%, respectively. In multivariate analysis, clinical stage (hazard ratio [HR] 2.28, 95% confidence interval [CI] 1.40-3.73, p = 0.001) and the geriatric nutritional risk index (GNRI, HR 0.95, 95% CI 0.92-0.97, p < 0.001) were significant prognostic factors of OS. Clinical stage (HR 2.06, 95% CI 1.34-3.18, p = 0.001), tumor location (HR 2.04, 95% CI 1.39-3.01, p < 0.001) and GNRI (HR 0.96, 95% CI 0.94-0.99, p = 0.003) were significant prognostic factors of PFS. CONCLUSION: Clinical stage and GNRI were significant prognostic factors of OS and PFS. Tumor location was a significant prognostic factor of PFS. These prognostic factors might be useful for decision-making for elderly patients with esophageal cancer.

Why not de-intensification for uterine cervical cancer?

OBJECTIVE: The majority of uterine cervical cancer is known to be related to human papillomavirus (HPV), and HPV-related tumors are known to be radio-sensitive. In the management of HPV-related oropharyngeal cancer, de-intensification of treatment has been attempted; however, no such attempt is performed in the management of cervical cancer. The aim of this study was to identify a group of patients who can safely be treated by de-escalated treatment intensity. METHODS: From the Asian international multi-institutional retrospective study involving 13 Japanese, one Thailand, and one Korean institutions based on 469 patients, squamous cell carcinoma (Scc), tumor reduction ratio ≥29%, tumor size before brachytherapy ≤4 cm, and total treatment time (TTT) <9 weeks were identified as factors having an influence on local control. Based on these findings, low-risk patients having these four factors were extracted, and treatment outcomes categorized in 10 Gy increment of CTVHR D90 were compared. RESULTS: Among 469 patients, 162 patients (34.5%) met the criteria of low-risk group, and 63, 41, 43, and 15 patients were categorized in CTVHR D90 50-60 Gy, 60-70 Gy, 70-80 Gy, and >80 Gy, respectively. While 4-y progression-free survival ranged from 66 to 80%, 4-y local control was consistently over 90% in every dose group. Rectum and bladder D2cc and incidence of late adverse events decreased as CTVHR D90 decreased. CONCLUSIONS: The low-risk patients achieved favorable local control with CTVHR D90 <80 Gy. A personalized treatment strategy based on tumor response could also be adopted for cervical cancer.

IMRT improves local control in patients with nasopharyngeal carcinoma compared with conventional radiotherapy: propensity score-matched analysis.

BACKGROUND: It is still controversial whether intensity-modulated radiotherapy has an obvious advantage over conventional radiotherapy. The purposes of this study were to evaluate prognostic factors in pre-treatment characteristics for nasopharyngeal carcinoma and to compare treatment outcomes in patients who received intensity-modulated radiotherapy and patients who received two-dimensional radiotherapy or three-dimensional radiotherapy. METHODS: We reviewed patients with nasopharyngeal carcinoma who received chemoradiotherapy in our hospital during the period from 2000 to 2017, and we excluded patients who had a history of surgery for nasopharyngeal carcinoma and those who had distant metastases before treatment. A total of 72 patients who were treated by radiotherapy with concurrent chemotherapy were enrolled. All of the patients were irradiated with a total dose of 58-70 Gy. Overall survival, locoregional control and progression-free survival rates were compared in the groups treated by intensity-modulated radiotherapy and two-dimensional/three-dimensional radiotherapy. Propensity score matching was performed to homogenize the two groups. RESULTS: The median follow-up period was 62.5 months. After propensity score matching, in patients treated with intensity-modulated radiotherapy, the 5-year rate of overall survival, locoregional control and progression-free survival were 73.5, 95.2 and 72.7%, respectively. In patients treated with two-dimensional/three-dimensional radiotherapy, the 5-year rate of overall survival, locoregional control and progression-free survival were 69.1, 67.7 and 51.8%, respectively. There was a significant difference between the groups only in locoregional control. Late toxicities of grade 2 or higher were occurred in 38.5 and 24.2% of the patients treated by two-dimensional/three-dimensional radiotherapy and intensity-modulated radiotherapy, respectively. CONCLUSIONS: Our results suggested that intensity-modulated radiotherapy is more effective than two-dimensional/three-dimensional radiotherapy in patients with nasopharyngeal carcinoma, especially in locoregional control.

The Impact of Histological Subtype on Survival Outcome of Patients with Stage IIB-IVA Cervical Cancer Who Received Definitive Radiotherapy.

The impact of histologic subtype on definitive radiotherapy for patients with locally advanced cervical cancer remains unclear. The aim of this retrospective analysis was to assess clinicopathological findings and clinical outcome by histological type in patients with stage IIB-IVA cervical cancer. Ninety-two patients with stage IIB-IVA [International Federation of Gynecology and Obstetrics (FIGO) 2008] cervical cancer, who underwent definitive radiotherapy between 2013 to 2018, were identified as eligible for this study. The clinical information of the eligible patients was obtained from medical records of our hospital. Seventy-eight patients underwent concurrent chemoradiotherapy, and the remaining 14 patients received radiotherapy alone. Of 92 patients, 83 had squamous cell carcinoma (SCC) and 9 had non-SCC histology. Progression-free survival (PFS) rate of patients with non-SCC was significantly worse than of those with SCC (2-year PFS: 62.0% vs. 12.5%, p = 0.0020), but overall survival (OS) rate did not statistically differ between the two subtypes (2-year OS: 82.4% vs. 62.5%, p = 0.2157). Pelvic failure-free (PFF) rate of patients with non-SCC histology was significantly worse than of those with non-SCC (2-year PFF; 88.2% vs. 25.0%, p < 0.0001). In univariate analysis, non-SCC histology was associated with PFS rate, although there was no association with OS rate. In multivariate analysis, non-SCC histology and lymph node metastasis were independent prognostic factors for shorter PFS. In patients with stage IIB-IVA cervical cancer who underwent definitive radiotherapy, patients with non-SCC showed significantly worse PFS rate than those with SCC.

Development of a physical geometric phantom for deformable image registration credentialing of radiotherapy centers for a clinical trial.

PURPOSE: This study aimed to develop a physical geometric phantom for the deformable image registration (DIR) credentialing of radiotherapy centers for a clinical trial and tested the feasibility of the proposed phantom at multiple domestic and international institutions. METHODS AND MATERIALS: The phantom reproduced tumor shrinkage, rectum shape change, and body shrinkage using several physical phantoms with custom inserts. We tested the feasibility of the proposed phantom using 5 DIR patterns at 17 domestic and 2 international institutions (21 datasets). Eight institutions used the MIM software (MIM Software Inc, Cleveland, OH); seven used Velocity (Varian Medical Systems, Palo Alto, CA), and six used RayStation (RaySearch Laboratories, Stockholm, Sweden). The DIR accuracy was evaluated using the Dice similarity coefficient (DSC) and Hausdorff distance (HD). RESULTS: The mean and one standard deviation (SD) values (range) of DSC were 0.909 ± 0.088 (0.434-0.984) and 0.909 ± 0.048 (0.726-0.972) for tumor and rectum proxies, respectively. The mean and one SD values (range) of the HD value were 5.02 ± 3.32 (1.53-20.35) and 5.79 ± 3.47 (1.22-21.48) (mm) for the tumor and rectum proxies, respectively. In three patterns evaluating the DIR accuracy within the entire phantom, 61.9% of the data had more than a DSC of 0.8 in both tumor and rectum proxies. In two patterns evaluating the DIR accuracy by focusing on tumor and rectum proxies, all data had more than a DSC of 0.8 in both tumor and rectum proxies. CONCLUSIONS: The wide range of DIR performance highlights the importance of optimizing the DIR process. Thus, the proposed method has considerable potential as an evaluation tool for DIR credentialing and quality assurance.