Journal of Radiation Research最新文献

The purpose of this study was to design a radiogenomics machine learning-DeepSurv model for biochemical recurrence-free (BCR-free) survival and treatment response (TR) prediction for radiotherapy (RT) of prostate cancer (PCa). In this study, radiomic features were extracted from pre and post treatment multiparametric MRI (mpMRI), including T2-weighted (T2W), diffusion-weighted MR imaging (DWI) and apparent diffusion coefficient (ADC). Also, genomic biomarkers such as Ki-67 (a cell proliferation marker reflecting tumor growth activity and also prognostic information in cancer progression), PTEN (tumor suppressor gene regulating cell growth and survival, have a prominent role for TR and cancer progression) and Decipher (a genomic signature predicting cancer recurrence risk and TR based on gene expression patterns) were collected. Radiomics feature selection and dimensionality reduction methods were employed, followed by training machine learning (ML) models. Moreover, time to event data and survival models including Random Survival Forest (RSF) and DeepSurv neural networks were used. For model performance, the concordance index (C-index) and integrated Brier score (IBS), and for improving interpretability, the SHapley Additive exPlanations (SHAP) were applied. Radiomic feature of MRI including Kurtosis demonstrated a near-perfect positive correlation with Ki-67 expression (r = 0.64), however skewness showed a strong negative correlation with PTEN status (r = -0.88). Entropy and kurtosis of MRI were also highly correlated with the Decipher genomic risk score (r = 0.90 and r = -0.96, respectively). The integrated ML-DeepSurve model performance overall F1-score was 0.93 for TR. The model also offered robust stratification for patients based on BCR-free survival probability. Our findings underscore the potential of radiogenomic signatures as non-invasive biomarkers to personalized PCa RT decisions and provide a novel clinically explainable predictive model based on radiomic and molecular biomarkers for BCR-free survival and TR of mentioned cancer.

We have previously reported that the localized application of gaseous plasma to normal tissues suppresses distant tumor growth in mice, resembling the abscopal effect of radiotherapy. Plasma, a partially ionized gas generated by a high-voltage electrical discharge, is fundamentally distinct from ionizing radiation and produces diverse reactive oxygen and nitrogen species that interact with biological tissues. This study examined the abscopal-like effects of normal tissue plasma treatment in BALB/c mice with subcutaneous Colon 26 tumors. The left dorsal skin, 2-3 cm from the tumor, was exposed to plasma for 10 min per day for 5 consecutive days, which delayed the growth of distant tumors. Similar tumor suppression was observed with abdominal exposure, indicating that the effect was not site-specific. In C.B-17 SCID mice (lacking T and B cells) and BALB/c nu/nu mice (lacking T cells), dorsal treatment did not suppress tumor growth, suggesting that T cells are likely involved in the response. Flow cytometric analysis of tumor-infiltrating immune cells in BALB/c mice revealed significant reductions in macrophages and increases in monocytes, with a possible but nonsignificant increase in dendritic cells. No consistent changes were detected in CD8+ T-cell proportion or ICOS (inducible T-cell costimulatory) expression. However, the lack of antitumor effects in immunodeficient mice suggests that CD8+ T cells are involved.

This study aimed to establish the diagnostic reference levels (DRLs) of imaging doses for image-guided radiotherapy (IGRT) used in intensity-modulated radiotherapy for prostate cancer in Japan. A nationwide survey was conducted to gather data on image acquisition conditions, parameters, and frequencies across 193 radiation therapy institutions using intensity-modulated radiotherapy. IGRT modalities, such as kilovoltage and megavoltage cone-beam computed tomography (CBCT), two-dimensional imaging, and in-room computed tomography (CT), were targeted. Data analysis focused on image acquisition parameters displayed by the devices, such as tube voltage, current, and imaging dose, along with the CT dose index volume (CTDIvol) and dose-length product (DLP), were collected from 222 radiotherapy devices. The results showed that kV-CT/CBCT was the most frequently used modality, used in 94% of the institutions. Imaging dose-reduction techniques were adopted by over half of the institutions, with 56% optimizing imaging parameters and 45% reducing the imaging field size or scan length. The 75th percentile for CTDIvol was 16.0 mGy, while that for DLP was 263 mGy·cm, with considerable variation among devices and institutions. This study provides the first large-scale reference data for IGRT imaging doses used for prostate cancer treatment in Japan. These results are critical for improving patient safety by optimizing imaging protocols and establishing DRLs tailored to IGRT. These findings will serve as a basis for further refinement of radiological protection practices in Japan.

Boron Neutron Capture Therapy (BNCT) is a targeted radiotherapy that utilizes the nuclear reaction of 10B with thermal neutrons to destroy tumor cells while sparing healthy tissue. Its effectiveness relies on accurately modeling boron distribution. Current treatment planning systems use a fixed tumor-to-normal tissue (T/N) boron ratio, ignoring pharmacokinetics. This study improves BNCT dose calculations by integrating time-dependent boron concentrations from pharmacokinetic simulations. Firstly, this research improved the traditional two-compartment pharmacokinetic model to a three-compartment model to better represent boron distribution, accounting for different tumor locations. Two patient cases were simulated, and the comparisons were performed between the dose distributions obtained by the fixed T/N ratio method and the ones obtained by our pharmacokinetic-based approach. Results showed significant discrepancies between the two methods, with the maximum dose deviation in the tumor region reaching 11.386%. The pharmacokinetic-based method provided more accurate and individualized dose calculations. Secondly, the multi-objective optimization using the Basin Hopping algorithm was employed to determine the optimal irradiation time periods. This approach enhanced treatment efficacy by increasing the average dose and maximum dose in the gross tumor volume by ~4% within the same irradiation period, while minimizing damage to normal tissues. The optimized irradiation schedules resulted in improved dose delivery to the tumor while maintaining safe levels for normal tissues. Our findings highlight the importance of integrating pharmacokinetic data into BNCT treatment planning to improve dose accuracy and treatment outcomes.

Spacers separating the tumor from adjacent organs help improve irradiation dose parameters. We introduce a new hyaluronate gel spacer with MEIJI (ADANT®) as an alternative to the previously used Suvenyl® and its injection technique for cervical cancer brachytherapy. Five patients with cervical cancer underwent hyaluronate gel injection (HGI) with the MEIJI hyaluronate gel in their rectovaginal and vesicovaginal septa. The minimum doses covering 90% of the high-risk clinical target volume (CTVHRD90%), the most exposed 2 cc (D2cc) of organs at risk per session, as well as the total doses for combined external beam radiotherapy (with a central shield) and brachytherapy, were assessed. The median CTVHRD90% was 9.3 (range, 6.4-9.7) Gy per session and 92.2 Gy in the equivalent dose in 2 Gy fractions (EQD2) (80.3-93.3 Gy-EQD2) overall. The median rectum D2cc was 2.9 (1.8-5.0) Gy per session and 45.4 (43.4-57.1) Gy-EQD2 overall. The median D2cc of the bladder (bladder D2cc) was 4.8 (2.4-6.5) Gy per session and 64.6 (62.3-69.6) Gy-EQD2 overall. The MEIJI spacer disappeared within 3 or 7 days with no adverse events associated with HGI or deterioration of the patients' quality of life. MEIJI HGI facilitates a sufficient CTVHRD90% while keeping the rectal and bladder D2cc within dose constraints, even when the rectum and bladder are in close proximity to the CTVHR. In conclusion, the MEIJI spacer may help appropriately meet dose constraints, thereby potentially contributing to improving local control and/or reducing adverse events for patients receiving radiotherapy for cervical cancer.

This study presented a quantitative analysis of the differences in the depths of the distal 50% of acquired and estimated positron emission tomography (PET) images for 18 patients who had a total of 109 titanium (Ti) metal-surgical clips implanted after breast-conserving surgery. Offline PET/computed tomography (PET/CT) images were acquired after proton irradiation. Hounsfield Unit modifications were applied to correct for metal artifacts induced by the Ti clips in the planning CT scans of the soft tissues surrounding the clips. The positron-emitting-isotope PET distribution was calculated through Range-Verification scripting. Quantitative analysis was conducted on the depth differences at the distal 50% R50 of the PET and the calculated PET distribution. Using the R50 method, the depth verification results of the clips and the normal tissues were compared. The R50 method calculates the positional difference at the half-maximum value 2 cm from the skin, with clips beyond this position not affecting the results. Analyses of the regions around the Ti clips were conducted. The depth difference for Ti < 2 cm (where the depth of the clips from the skin was <2 cm) was -1.63 ± 1.08 mm, while the corresponding normal tissue (Ticont) showed a depth difference of -1.79 ± 1.15 mm. There was no statistically significant difference in the depth differences between Ti < 2 cm and the corresponding Ticont. This study utilized offline PET verification to demonstrate that applying tissue corrections based on surgical clips and surrounding muscle tissues in clinical practice ensures that the presence of surgical clips does not compromise the precision of proton dose delivery at the surgical site.

From simple viruses to complex multicellular animals, ionizing radiation can have deleterious effects on all organisms. For humans, exposure to radiation can come from a wide range of sources such as environmental contamination, occupational hazards, radiotherapy and space flight. In the next few decades, radiation toxicity will become an increasing healthcare concern as nuclear power usage, risk of nuclear war, space-based industry and cancer incidence are all projected to increase. While the biology of acute radiation sickness is relatively well understood, ionizing radiation can also cause severe chronic effects whose molecular and cellular basis remain largely a mystery. This is partly because complications that arise months or even years after exposure depend on tissue-level responses, and so there are aspects of late radiation toxicity that can only be investigated in vivo. We suggest that Drosophila melanogaster can contribute to understanding this phenomenon. To this date, Drosophila radiation research has been heterogenous in terms of dose, radiation type and developmental stage of exposure, but despite this a pattern of observations suggest that fruit flies experience both short- and long-term radiation injury. Moreover, the genetic underpinning of the Drosophila radiation response seems conserved with that of humans. We propose that Drosophila is well-suited to model radiation damage to tissues, highlighting the potential of the fly to inform clinical radiobiology research.

Total neoadjuvant therapy (TNT) improves oncological outcomes in locally advanced rectal cancer (LARC); however, treatment-induced lymphopenia remains a concern. We analyzed 74 patients undergoing three TNT regimens: long-course chemoradiotherapy with consolidation chemotherapy (LCCRT-CNCT), short-course radiotherapy with CNCT (SCRT-CNCT), and induction chemotherapy with LCCRT (INCT-LCCRT). Severe radiation-induced lymphopenia (RIL, Grade ≥ 3) occurred in 48%, 24%, and 54%, respectively (P = 0.126). In the LCCRT-CNCT group, large bowel irradiation (V35 Gy > 46 cc) was significantly associated with severe RIL in univariable analysis but not in multivariable models (P = 0.227), and in an exploratory combined analysis of LCCRT-CNCT and INCT-LCCRT, this showed a trend (P = 0.093). Pre-TNT absolute lymphocyte count (ALC) was an independent predictor of RIL. Small bowel irradiation (V15 Gy > 104 cc) predicted severe lymphopenia during chemotherapy in the univariable analysis; but multivariable analysis suggested pre-TNT ALC as the main factor, showing a trend toward significance (P = 0.051). In the SCRT-CNCT group, pre-TNT ALC was the only significant factor for severe lymphopenia in both the RT and chemotherapy phases in univariable analysis. Severe RIL significantly prolonged lymphocyte recovery time (median, 283 vs. 76 days, P < 0.001), whereas immune recovery did not differ according to the TNT regimen. The median ALC at the last follow-up was 86% of the baseline value, indicating incomplete recovery. While pre-TNT ALC correlated with lymphopenia risk, minimizing bowel irradiation may help mitigate treatment-induced immunosuppression. Prospective studies are required to validate these findings.

In recent years, there has been growing interest in cardiac toxicity following radiation therapy (RT) for esophageal cancer; however, detailed incidence and risk factors in Japanese patients remain unclear. The purpose of this study was to clarify the incidence, timing, risk factors, and dose-volume relationships of multiple cardiac toxicities, including pericardial effusion, heart failure, arrhythmia, cardiac valve disease and acute coronary syndrome. We retrospectively analyzed patients of thoracic esophageal cancer without distant metastasis who were treated with curative RT at our hospital between 2007 and 2020. Cardiac toxicity events were graded according to common terminology criteria for adverse events v5.0. Association between cardiac dose-volume parameters and grade 2 or higher toxicity was analyzed using logistic regression analysis. The analysis included 250 patients, with a median follow-up period of 21 months. The 2-year cumulative incidence of grade 2 or higher pericardial effusion, heart failure, arrhythmia, and acute coronary syndrome were 36.6%, 0.4%, 1.4%, and 1.3%, respectively. Logistic regression analysis identified the volume of the whole heart receiving 30Gy as a significant risk factor for grade 2 pericardial effusion (OR, 1.03; 95% confidence interval [CI], 1.01-1.04; P < 0.01) and grade 2 arrhythmia (OR, 1.10; 95%CI, 1.02-1.18; P = 0.01). We reported detailed profile of cardiac toxicity in Japanese patients who received curative RT for esophageal cancer. Reducing cardiac radiation dose may reduce the risk of pericardial effusion and arrhythmia.