Tomoki Kitagawa

Purpose: We aimed to evaluate the efficacy and safety of re-irradiation stereotactic body radiation therapy (SBRT) in patients with metastatic epidural spinal cord compression (MESCC) following high-dose conventional radiotherapy. Materials and methods: Twenty-one patients met the following eligibility criteria: with an irradiation history of 50 Gy₂ equivalent dose in 2-Gy fractions (EQD2) or more, diagnosed MESCC in the cervical or thoracic spines, and treated with re-irradiation SBRT of 24 Gy in 2 fractions between April 2018 and March 2023. Prior treatment was radiotherapy alone, not including surgery. The primary endpoint was a 1-year local failure rate. Overall survival (OS) and treatment-related adverse events were assessed as the secondary endpoints. Since our cohort includes one treatment-related death (TRD) of esophageal perforation, the cumulative esophageal dose was evaluated to find the dose constraints related to severe toxicities. Results: The median age was 68, and 14 males were included. The primary tumor sites (esophagus/lung/head and neck/others) were 6/6/7/2, and the median initial radiotherapy dose was 60 Gy₂ EQD2 (range: 50–105 Gy₂, 60–70/ > 70 Gy₂ were 11/4). Ten patients underwent surgery followed by SBRT and 11 SBRT alone. At the median follow-up time of 10.4 months, 17 patients died of systemic disease progression including one TRD. No radiation-induced myelopathy or nerve root injuries occurred. Local failure occurred in six patients, with a 1-year local failure rate of 29.3% and a 1-year OS of 55.0%. Other toxicities included five cases of vertebral compression fractures (23.8%) and one radiation pneumonitis. The cumulative esophageal dose was recommended as follows: D_max < 203, D_0.035 cc < 187, and D_1cc < 167 (Gy₃ in biological effective dose). Conclusion: Re-irradiation spine SBRT may be effective for selected patients with cervical or thoracic MESCC, even with high-dose irradiation histories. The cumulative dose assessment across the original and re-irradiated esophagus was recommended to decrease the risk of severe esophageal toxicities.

Purpose: This retrospective study aimed to assess the efficacy and safety of palliative radiotherapy for painful non-bone lesions in patients with advanced cancer. Materials and methods: We enrolled patients with painful non-bone lesions who underwent conventional palliative radiotherapy between September 2018 and September 2022. The treatment targets included primary tumor lesions, lymph node metastases, non-bone hematogenous metastases, and other lesions. The primary endpoint was the overall pain response rate in evaluable patients, determined based on the International Consensus Pain Response Endpoint criteria. The secondary endpoints included overall survival, pain recurrence, and adverse events. Results: Of the 420 screened patients, 142 received palliative radiotherapy for painful non-bone lesions, and 112 were evaluable. A pain response was achieved in 67 patients (60%) of the 112 evaluable patients within a median of 1.2 months. Among these patients, 25 exhibited complete response, 42 partial response, 18 indeterminate response, and 27 pain progression. The median survival time was 5.5 months, recorded at a median follow-up of 6.0 months, during which 67 patients died. Multivariate analysis identified poor performance status scores of 2–4, opioid use, and re-irradiation as independent factors associated with a reduced likelihood of achieving a pain response. Pain recurrence occurred in 18 patients over a median of 4.1 months. Seventeen patients had grade 1–2 adverse events, while none experienced grade 3 or higher toxicity. Conclusion: Palliative radiotherapy can potentially be a safe and well-tolerated modality for managing painful non-bone lesions, with a low rate of adverse events.

Purpose: This study evaluated the trends in the platform for stereotactic radiotherapy to the brain (SRT), utilizing the open data of the National Database published by the Ministry of Health, Labour, and Welfare. Materials and methods: This study analyzed data from FY2014 to FY2021. The practices included in the study were gamma knife surgery (GKS) and SRT with a linear accelerator (LINAC). The total number of outpatient and inpatient cases in each SRT system was evaluated annually. Results: From April 2014 to March 2022, the study included 212,016 cases (102,691 GKS and 109,325 LINAC) of the registered 1,996,540 radiotherapy cases. In the first year, 13,117 (54.1%) cases were GKS, and 11,128 (45.9%) were LINAC; after that, GKS decreased, and LINAC increased, reaching the same rate in FY2017. Compared to the first year, the final year showed 11,702 GKS (− 1415 or − 10.8%) and 17,169 LINAC (+ 6041 or + 54.3%), with an increase of 4626 total SRT cases to 28,871 (+ 19.1%). The percentage of outpatient treatment also increased from 4.6 to 11.8% for GKS and from 44.7 to 57.9% for LINAC. Conclusion: The study found a gradual decrease in the selection of GKS, an increasing trend in the selection of LINAC, and an increase in the overall number of stereotactic irradiations. In particular, the proportion of outpatient treatment increased, indicating that more than half of LINAC was selected for outpatient treatment.

Aim This study aimed to evaluate the clinical benefits of systemic therapy (ST) combined with stereotactic radiosurgery (SRS) for brain metastases (BM). Methods The patient data were extracted from the institutional disease database from 2016 to 2021. Surgical and whole-brain radiotherapy cases and poor Karnofsky performance status (KPS < 70) were excluded. The eligible patients were divided into monotherapy (SRS alone or ST alone) and combined therapy (SRS and ST, combined within a month). Univariate and multivariate Cox proportional hazards analyses were used to examine factors associated with increased risk of death and intracranial progression. The propensity score for selecting treatment was calculated based on existing prognostic covariates. Two groups were matched 1:1 and compared for intracranial progression-free survival (PFS) and overall survival (OS). Results We identified 1605 patients and analyzed 928 (monotherapy: n = 494, combined therapy: n = 434). In a multivariable model, the combined therapy was independently associated with improved PFS and OS relative to the monotherapy. At the median follow-up of 383 days in the matched dataset, the combined therapy group showed significantly longer PFS (median, 7.4 vs. 5.0 months, P < 0.001) and OS (median, 23.1 vs. 17.2 months, P = 0.036) than the monotherapy group. The overall intracranial progression and mortality risk was reduced in the combined therapy group, with an estimated HR of 0.70 and 0.78. Conclusions Combined therapy exhibited longer PFS and OS than monotherapy in BM patients. The results support the recent trend toward combining systemic and local therapies, encouraging future clinical trials.

In this study, a prototype device was developed to quickly remove the mask used to immobilize the head and neck by remotely releasing the quick fasteners. As a first step in investigating the usefulness of this prototype, we performed repeated removal tests and examined the accuracy of dose calculation. The results showed that the quick-release fasteners of a Type-S system (CIVCO Medical Solutions, Iowa, USA) could be removed remotely and accurately (success rate: 100%). Additionally, the dose errors in treatment planning were negligible (< 1.0%), and the gamma pass rate was equivalent (99.9%). Therefore, this prototype device with a remote system would help manage patient safety in emergencies, such as a disaster or a sudden change in the patient's condition. However, age-related deterioration with long-term clinical use or its ability to link with beam-off still requires further exploration.

Gold nanoparticles (AuNPs) can be used with megavolt (MV) X-rays to exert radiosensitization effects, as demonstrated in cell survival assays and mouse experiments. However, the detailed mechanisms are not clear; besides physical dose enhancement, several chemical and biological processes have been proposed. Reducing the AuNP concentration while achieving sufficient enhancement is necessary for the clinical application of AuNPs. Here, we used positively charged (+) AuNPs to determine the radiosensitization effects of AuNPs combined with MV X-rays on DNA damage in vitro. We examined the effect of low concentrations of AuNPs on DNA damage and reactive oxygen species (ROS) generation. DNA damage was promoted by 1.4 nm +AuNP with dose enhancement factors of 1.4 ± 0.2 for single-strand breaks and 1.2 ± 0.1 for double-strand breaks. +AuNPs combined with MV X-rays induced radiosensitization at the DNA level, indicating that the effects were physical and/or chemical. Although −AuNPs induced similar ROS levels, they did not cause considerable DNA damage. Thus, dose enhancement by low concentrations of +AuNPs may have occurred with the increase in the local +AuNP concentration around DNA or via DNA binding. +AuNPs showed stronger radiosensitization effects than −AuNPs. Combining +AuNPs with MV X-rays in radiation therapy may improve clinical outcomes.

Background: This study aimed to investigate preoperative spirometry and BMI as early predictors of the mean heart and lung dose (MHD, MLD) in deep inspiration breath-hold (DIBH) radiotherapy. Methods: Left-sided breast cancer patients underwent breast-conserving surgery followed by DIBH radiotherapy enrolled. Patients who were not available for preoperative spirometry were excluded. One hundred eligible patients were performed free-breathing (FB-) CT and DIBH-CT for plan comparison. We completed the correlative and multivariate analysis to develop the linear regression models for dose prediction. The residuals were calculated to explore the unpreferable subgroups and compare the prediction accuracy. Results: Among the parameters, vital capacity (VC) and BMI showed the strongest negative correlation with MHD (r = − 0.33) and MLD (r = − 0.34), respectively. They were also significant in multivariate analysis (P < 0.001). Elderly and less VC were independent predictors of increasing absolute residuals (AR). The VC model showed no significant difference in AR compared to the model using the CT parameter of lung volume in FB (LV-FB): median AR of the LV-FB model vs. the VC model was 0.12 vs. 0.11 Gy (P = 0.79). On the other hand, the median AR of the MLD model was 0.38 Gy, showing no specific subgroups of larger AR. Conclusion: Preoperative spirometry and BMI are significant predictors of MHD and MLD, respectively. Although elderly and low-VC patients may have larger predictive variations, spirometry might be a substitute for LV-FB as a predictor of MHD.

Objective: To clarify the peripheral dose changes, especially in the eye lens and thyroid gland regions, using an acrylic-lead shield in cone-beam computed tomography (CBCT).Methods: The acrylic-lead shield consists of system walls and a system mat. The radiophotoluminescence glass dosemeter was set on the eye lens and thyroid gland regions on the RANDO phantom. The system mat was laid under the RANDO phantom ranging from the top of the head to the shoulders, and then, the system walls shielded the phantom’s head. Additionally, the phantom was covered anteriorly with a band that had the same shielding ability as the system mat to cover the thyroid gland region. Protocols for CBCT imaging of the thoracic or pelvic region in clinical practice were used. The measurement was performed with and without the acrylic-lead shield.Results: The dose to the eye lens region was reduced by 45% using the system wall. Conversely, the dose to the thyroid gland was unchanged. The use of the system mat reduced the dose to the thyroid gland region by 47%, and the dose to the eye lens was reduced by 22%. The dose to the eye lens region decreased to the background level using the system walls and mat.Conclusion: The newly proposed device using an acrylic-lead shield reduced the peripheral dose in CBCT imaging.Advances in knowledge: Attention is focused on managing peripheral dose in image-guided radiation therapy. The peripheral dose reduction using the acrylic-lead shield is a new proposal in radiotherapy that has never been studied.