Journal of Radiation Research最新文献

We aimed to compare dose to organs at risk (OARs) and the excess relative risk (ERR) of cardiac mortality among three-dimensional conformal radiotherapy (3D-CRT), volume modulated arc therapy (VMAT) and proton beam therapy (PBT) in craniospinal irradiation (CSI). CSI plans of 3D-CRT, VMAT and PBT were generated. Vertebral body reduced dose (VBR)-CSI according to the International Society of Paediatric Oncology recommendation was used for VMAT and PBT. We delineated two sets of target volumes, i.e. target volume (TV) 1 for brain and thecal sac and TV2 for the vertebral body. Two sets of CSI dose, 23.4 and 36 Gy, were prescribed for TV1, and VBR doses, 18.4 and 20 Gy, were prescribed for TV2. For 3D-CRT, we prescribed a dose only to cover TV1. For VMAT and PBT, 23.4/18.4Gy and 36/20 Gy in 13 and 20 fractions were optimized. To evaluate the ERR of cardiac mortality compared with the normal population, we incorporate the mean heart dose with the linear model. In a total of eight patients, 48 treatment plans were generated (24 plans for each dose set). PBT showed the lowest mean dose to all OARs, i.e. heart, lung, liver, kidney, esophagus, oral cavity, thyroid and vertebral body. PBT showed significantly less ERR of cardiac mortality compared with 3D-CRT and VMAT for both 23.4 and 36 Gy prescriptions. With VBR-CSI, PBT reduced the mean dose to all OARs and significantly reduced the ERR of cardiac mortality compared with 3D-CRT and VMAT. The advantage of PBT was manifest, especially with high-dose CSI.

The brain and spinal cord, which constitute the central nervous system, were historically considered immune-privileged sites, as it was believed they lacked an equivalent to the systemic lymphatic system. However, in 2013, a pathway facilitating the clearance of waste products through the brain parenchyma via the perivascular space was proposed, garnering attention as the 'glymphatic system'. Similar to the systemic lymphatic system, the glymphatic system plays a critical role in immune responses and has been implicated not only in Alzheimer's disease and inflammatory brain disorders but also in conditions such as hydrocephalus and glaucoma, which are associated with cerebrospinal fluid circulation impairments. Recent studies have suggested that dysfunction of the glymphatic system may promote the progression of brain tumors and reduce the efficacy of immune responses and pharmacological therapies targeting tumors. Radiotherapy is a major treatment option for brain tumors; however, while it can enhance immune responses against tumors, it may also suppress these responses at the same time. Additionally, cranial irradiation has been suggested to impair the function of the glymphatic system. This review provides an overview of the structure and functional evaluation methods of the glymphatic system, summarizes the effects of its dysfunction on brain tumor treatment, and explores recent findings on the impact of radiation therapy on glymphatic system functioning. Lastly, it also explores the potential for radiation therapy strategies that account for their effects on the glymphatic system.

Fluoroscopy-guided bronchoscopy is an essential tool for diagnosing and treating lung diseases, particularly lung cancer. However, prolonged fluoroscopic exposure raises concerns regarding radiation-induced lens injuries in physicians, such as radiation cataracts. In response to the International Commission on Radiological Protection lowering the occupational lens dose limit to an average of 20 mSv/year over 5 years, there is an increasing need for effective lens protection during such procedures. This study has aimed to develop a novel lens protection device specifically designed for bronchoscopy physicians and evaluate its protective performance through a phantom study. The device consisted of a 0.175 mm lead (Pb) sheet positioned on the left side of the physician's head, secured with headgear to improve stability and comfort during prolonged use. A phantom study was conducted using a trunk phantom to simulate a patient and a head phantom to simulate a physician. The scattered radiation doses were measured at 15 locations on the phantom head using a radiophotoluminescence glass dosimeter, both with and without a protective device. The device demonstrated a protective effect of more than 80% for the left eye across all tested angles, whereas the right eye showed protection ranging from approximately 40% to 75% depending on the angle. This novel lens protection device has the potential to significantly reduce scattered radiation to the left eye while minimizing vision obstruction and discomfort. This offers a practical solution for radiation protection during bronchoscopy and may be applicable to other interventional procedures requiring fluoroscopic guidance.

Conventional fractionated radiotherapy (CFRT) for hepatocellular carcinoma (HCC) is limited by intrinsic radioresistance. In this study, we investigated the radiosensitizing potential of maraviroc, a chemokine receptor 5 (CCR5) antagonist, and its mechanistic basis in HCC. A murine HCC model was established by subcutaneous implantation of H22 cells into the hind limbs of mice. Tumor-bearing mice received CFRT with or without maraviroc, and tumor growth kinetics were evaluated. Systemic levels of myeloid-derived suppressor cells (MDSCs) in peripheral blood and plasma chemokine ligand 5 (CCL5) were longitudinally monitored post-irradiation. In vitro mechanistic studies utilized maraviroc combined with conditioned media from 2 Gy-irradiated H22 cells to dissect its radiosensitizing effects. H22 cell viability, proliferation and migration were assessed following irradiation with or without maraviroc. Flow cytometry was employed to quantify polymorphonuclear MDSC (PMN-MDSC) proliferation, differentiation and immunosuppressive capacity via T-cell proliferation assays. Compared to monotherapy with either CFRT or maraviroc alone, maraviroc combined with CFRT significantly inhibited HCC growth in the mouse model. In vitro, maraviroc did not directly enhance irradiation-induced H22 cell death or suppress proliferation but reversed PMN-MDSC-mediated immunosuppression by attenuating PMN-MDSC migration and abrogating PMN-MDSC suppression of T-cell proliferation. Maraviroc combined with CFRT significantly inhibited the differentiation of bone marrow cells into PMN-MDSCs. In conclusion, the synergistic application of CCR5 antagonist with CFRT significantly enhanced radiosensitivity in HCC, primarily through suppression of PMN-MDSCs differentiation and migration, coupled with blockade of their T-cell proliferation inhibitory functions.

Cancer stem cell (CSC) radioresistance is a major cause of radiotherapy (RT) failure and tumor recurrence. The molecular target for eradicating CSCs has not been identified despite research efforts to overcome tumor radioresistance. The adenosine monophosphate-activated protein kinase (AMPK) is responsible for transmitting nuclear DNA damage signals to the mitochondria, which in turn generate adenosine triphosphate to execute a DNA damage response. Disruption of this mitochondria-mediated genomic defense mechanism may be an effective strategy to enhance the cytotoxic efficacy of RT. Here, we investigated the potential efficacy of the pan-AMPK inhibitor dorsomorphin (Dor) in preventing CSC radioresistance. Radioresistant cancer stem-like cells were derived from the human liver cancer cell line HepG2 (HepG2 82FR-31NR). The radiosensitizing effect of Dor was then examined in HepG2 82FR-31NR cell cultures by clonogenic assays. Low-dose Dor markedly suppressed the recovery of HepG2 cancer stem-like cells after radiation but had little effect on normal fibroblast proliferation and survival, whether applied alone or in combination with radiation. In conclusion, this study strongly suggests that Dor treatment can radiosensitize cancer stem-like cells at doses that have no significant cytotoxic effects on normal human fibroblasts.

The recommended dwell time weight of the needle in intracavitary/interstitial hybrid brachytherapy (HBT) has been 10-20%. This study aimed to investigate the correlation between the weight constraint of the needle and normal organ doses in uterine cervical cancer HBT. This study included 30 cervical cancer patients who received HBT with tandem/ovoid applicators. In our clinical practice, treatment plans were generated without the constraint of the dwell time weight of the needle. The cases where this weight exceeded 20% were replanned. An inverse planning technique with locking downscaled needle dwell time was used to reproduce isodose lines of clinical plans. Replanning repeated with downscaling of the dwell time until the weight of the needle fell <20% (Needle-Lock plan). The Needle-Lock plans were rescaled to coincide with the high-risk clinical target volumes D90 of clinical plans. D2cc in normal organs and the overdose area >200% of the prescribed dose were evaluated. In 17 of 30 (56.7%) clinical plans, the weight of the needle exceeded 20%. The rectum, bladder and sigmoid colon D2cc significantly increased with the Needle-Lock plan. The overdosage area also increased significantly (P < 0.01). The correlations between the needle number and the increase of D2cc in the rectum and sigmoid colon (P < 0.01) were statistically significant. Limiting needle dwell time weight by 10-20% increased bladder and rectum doses, especially with multiple needles. These findings suggest that needle dwell time weight recommendations could need to be reconsidered based on individual and institutional situation.

This study evaluated survival outcomes and prognostic factors in patients with bladder cancer treated with radiotherapy. A retrospective analysis was conducted on 488 patients across all cancer stages who received radiotherapy at two institutions between 1 January 2000 and 31 December 2022. Overall survival (OS) was assessed based on treatment intent (radical or palliative) and cancer stage. Among these patients, 304 with Stage II-III disease who underwent radical radiotherapy were further analyzed for OS and prognostic factors using Kaplan-Meier methods and Cox regression analysis. In the radical radiotherapy group, median survival times (MSTs) were 43 months for Stage 0-I, 29 months for Stage II-III, and 17 months for Stage IV (M0). In the palliative radiotherapy group, MSTs were 16 months (95% confidence interval [CI]: 11-25) for M0 and 9 months (95% CI: 7-15) for M1. Among the 304 patients with Stage II-III disease treated with radical radiotherapy, the 3-year OS rate was 43.0%. Hydronephrosis was the only independent prognostic factor significantly associated with worse OS (hazard ratio: 1.915, P < 0.001). Age, sex, stage, treatment era, prophylactic pelvic radiotherapy, chemotherapy and prescribed dose had no significant impact on OS. Radiotherapy remains a viable treatment option for patients at any stage of cancer. Although hydronephrosis negatively affects survival, it should not preclude the use of radiotherapy.

This study investigated the role of tumor immunogenicity in the ionizing radiation (IR)-induced abscopal effect. The ovalbumin-expressing B16 cell line (B16-OVA) served as a relatively immunogenic tumor model compared to the B16F10 cell line. C57BL/6 mice were implanted with B16-OVA or B16F10 in the left thigh as the primary tumor and B16F10 in the right thigh as the secondary tumor to evaluate the abscopal response. IR was applied solely to the primary tumor, followed by administration of isotype or anti-programmed cell death protein-1 (PD-1) antibodies. Tumor-infiltrating immune cells were analyzed using flow cytometry. B16-OVA tumors exhibited increased T-cell infiltration and elevated granzyme B and Ki-67 expression in CD8+ T cells compared to B16F10 tumors. IR delayed secondary tumor growth in B16-OVA-irradiated mice, but not in B16F10-irradiated mice. While CD8+ T-cell numbers increased in the secondary tumors of both groups, regulatory T cells significantly increased only in B16F10-irradiated mice. IR promoted differentiation from stem-like TCF1+TIM3- to effector-like TCF1-TIM3+ CD8+ T cells, with elevated granzyme B expression. Polyfunctional T cells co-expressing IFN-γ, TNF-α and IL-2 were significantly increased only in secondary tumors of B16-OVA-irradiated mice under PD-1 blockade. The abscopal effect was abolished by FTY720 treatment and CD8+ T-cell depletion. In conclusion, the IR-induced abscopal effect was dependent on the immunogenicity of the irradiated tumor. The findings may have implication on enhancing abscopal effect in clinical settings.

Intensity-modulated radiation therapy (IMRT) uses intensity-modulated photon beams from multiple directions to achieve conformal dose delivery to a target with a complex shape while reducing the dose to organs at risk. We analyzed the trends in IMRT utilization rates across Japanese prefectures from 2015 to 2019 and investigated their relationship with medical resources. Data from the National Database of Health Insurance Claims and the Japanese Society for Radiation Oncology Structure Survey were analyzed. IMRT utilization rates and medical resources (radiation oncologists, medical physicists, radiation technologists, and IMRT-capable linear accelerators) were assessed for all 47 prefectures. A mixed-model analysis was employed to examine the relationship between IMRT utilization rates and medical resources. IMRT utilization increased from 16.4% in 2015 to 22.0% in 2019, with significant regional disparities (range, <10% to >30%). Mixed-model analysis revealed that the number of IMRT-capable linear accelerators (estimate = 0.073, P < 0.01) and radiation oncologists (estimate = 0.032, P = 0.04) was significantly associated with higher IMRT utilization rates. Medical physicists and radiation technologists showed no significant association with IMRT utilization rates. Although the use of IMRT has increased in Japan, substantial regional disparities persist. Increasing the number of IMRT-capable linear accelerators and radiation oncologists may be the most effective strategy to improve equitable access to IMRT in Japan.