Non-coplanar Arc-Involved Beam Arrangement With Sufficient Arc Rotations Is Suitable for Volumetric-Modulated Arc-Based Radiosurgery for Single Brain Metastasis.

Introduction In linac-based stereotactic radiosurgery (SRS) leveraging a multileaf collimator (MLC) for brain metastasis (BM), volumetric-modulated arcs (VMAs) enable the generation of a suitable dose distribution with efficient planning and delivery. However, the arc arrangement, including the number of arcs, allocation, and rotation ranges, varies substantially among devices and facilities. Some modalities allow coplanar arc(s) (CA(s)) or beam(s) alone, and some facilities only use them intentionally despite the availability of non-coplanar arcs (NCAs). The study was conducted to examine the significance of NCAs and the optimal arc rotation ranges in VMA-based SRS for a single BM. Materials and methods This was a planning study for the clinical scenario of a single BM, including 20 clinical cases with a gross tumor volume (GTV) of 0.72-44.30 cc. Three different arc arrangements were compared: 1) reciprocating double CA alone of each 360º rotation with different collimator angles of 0 and 90º, 2) one CA and two NCAs of each 120º rotation with the shortest beam path lengths to the irradiation isocenter (NCA_L), and 3) one CA of 360º rotation and two NCAs of each 180º rotation (NCA_F). The three arcs were allocated similarly to equally divide the cranial hemisphere with different collimator angles of 0, 45, and 90º. Three VMA-based SRS plans were generated for each GTV using a 5 mm leaf-width MLC with the identical optimization method that prioritized the steepness of dose gradient outside the GTV boundary without any constraints to the GTV internal dose. A prescribed dose was uniformly assigned to the GTV D V-0.01 cc, the minimum dose of GTV minus 0.01 cc. The GTV dose conformity, the steepness of dose gradients both outside and inside the GTV boundary, the degree of concentric lamellarity of the dose gradients, and the appropriateness of the dose attenuation margin outside the GTV boundary were evaluated using metrics appropriate for each. Results The arc arrangements including NCAs showed significantly steeper dose gradients both outside and inside the GTV boundary with smaller dose attenuation margins than the CAs alone, while NCAs showed no significant advantage on the GTV dose conformity. In the NCA-involved arc arrangements, the NCA_F was significantly superior to the NCA_L in terms of the GTV dose conformity, the steepness of dose gradient outside the GTV, the degree of concentric lamellarity of the dose gradients outside and inside the GTV boundary, and the appropriateness of dose attenuation margin. However, the NCA_F showed no significant advantage on the steepness of dose increase inside the GTV boundary over the NCA_L. The dose increase just inside the prescribed isodose surface to the GTV boundary was significantly steeper with the NCA_L than the NCA_F. Conclusions In VMA-based SRS for a single BM, an arc arrangement including NCAs is indispensable, and sufficient arc rotations are suitable for achieving a dose distribution that maximizes therapeutic efficacy and safety in comparison to limited ones which are appropriate for dynamic conformal arcs. Although VMA with CAs alone can provide a non-inferior GTV dose conformity to NCAs, CA(s) alone should be applied only to situations where shorter irradiation time is prioritized over efficacy and safety.

Evaluation of the intramammary distribution of breast lesions detected by MRI but not conventional second-look B-mode ultrasound using an MRI/ultrasound fusion technique.

The objective of this study was to evaluate the intramammary distribution of MRI-detected mass and focus lesions that were difficult to identify with conventional B-mode ultrasound (US) alone. Consecutive patients with lesions detected with MRI but not second-look conventional B-mode US were enrolled between May 2015 and June 2023. Following an additional supine MRI examination, we performed third-look US using real-time virtual sonography (RVS), an MRI/US image fusion technique. We divided the distribution of MRI-detected mammary gland lesions as follows: center of the mammary gland versus other (superficial fascia, deep fascia, and atrophic mammary gland). We were able to detect 27 (84%) of 32 MRI-detected lesions using third-look US with RVS. Of these 27 lesions, 5 (19%) were in the center of the mammary gland and 22 (81%) were located in other areas. We were able to biopsy all 27 lesions; 8 (30%) were malignant and 19 (70%) were benign. Histopathologically, three malignant lesions were invasive ductal carcinoma (IDC; luminal A), one was IDC (luminal B), and four were ductal carcinoma in situ (low-grade). Malignant lesions were found in all areas. During this study period, 132 MRI-detected lesions were identified and 43 (33%) were located in the center of the mammary gland and 87 (64%) were in other areas. Also, we were able to detect 105 of 137 MRI-detected lesions by second-look conventional-B mode US and 38 (36%) were located in the center of the mammary gland and 67 (64%) were in other areas. In this study, 81% of the lesions identified using third-look US with RVS and 64% lesions detected by second-look conventional-B mode US were located outside the center of the mammary gland. We consider that adequate attention should be paid to the whole mammary gland when we perform third-look US using MRI/US fusion technique.

Consideration of Optimal Evaluation Metrics for Internal Gross Tumor Dose Relevant to Tumor Response in Multi-fraction Stereotactic Radiosurgery of Brain Metastasis.

Introduction In stereotactic radiosurgery (SRS) for brain metastasis (BM), the target dose inhomogeneity remains highly variable among modalities, irradiation techniques, and facilities, which can affect tumor response during and after multi-fraction SRS. Volumetric-modulated arcs (VMAs) can provide a concentrically-layered steep dose increase inside a gross tumor volume (GTV) boundary compared to dynamic conformal arcs. This study was conducted to review the optimal evaluation method for the internal GTV doses relevant to maximal response and local control, specifically to examine the significance of the doses 2 mm and 4 mm inside the GTV boundary in VMA-based SRS. Materials and methods This was a planning study for the clinical scenario of a single BM and targeted 25 GTVs of >0.50 cc, including eight spherical models with diameters of 10-45 mm and 17 clinical BMs (GTV: 0.72-44.33 cc). SRS plans were generated for each GTV using VMA with a 5-mm leaf-width multileaf collimator and the optimization that prioritized the steepness of the dose gradient outside the GTV boundary without any internal dose constraints. The dose prescription and evaluation were based on the GTV D V-0.01 cc, a minimum dose of GTV minus 0.01 cc. Two planning systems were compared for the GTV - 2 mm and GTV - 4 mm structures that were generated by equally reducing 2 mm and 4 mm from the GTV surface. The D eIIVs, a minimum dose of the irradiated isodose volume equivalent to the GTV - 2 mm and GTV - 4 mm, were compared to other common metrics. Results The GTV - 2 mm and GTV - 4 mm volumes differed significantly between the systems. In the spherical GTVs, the irradiated isodose surfaces of GTV D 80% and D 50% corresponded to 0.4-1.6 mm (<2 mm) and 1.0-4.6 mm inside the GTV boundary, respectively. In the 25 GTVs, the GTV - 2 mm coverage with the D eIIV varied from 83.7% to 98.2% (95-98% in 68% of the cases), while the GTV coverage with the GTV - 2 mm D eIIV was 20.2-75.9%. In the 23 GTVs of ≥1.26 cc, the GTV coverage with the GTV - 4 mm D eIIV varied from 1.9% to 55.6% (<50% in 87% of the cases). No significant difference was observed between the GTV D 50% and the GTV - 2 mm D eIIV, while the GTV - 4 mm D eIIV was significantly higher than the GTV D 50%. No significant correlations were observed between the GTV D 50% and the D eIIVs of the GTV - 2 mm and GTV - 4 mm. Conclusions The doses 2 mm and 4 mm inside a GTV have low correlations with the GTV D 50% and may be more relevant to maximal response and local control for SRS of BM. The D eIIV instead of the minimum dose of a fixed % coverage (e.g. D 98%) is suitable for reporting the doses 2 mm and 4 mm inside the GTV boundary in terms of avoiding the over- or under-coverage, with consideration to substantial variability in minus margin addition functions among planning systems. In VMA-based SRS with a steep dose gradient, the doses 2-4 mm inside a GTV decrease significantly as the GTV increases, which can attenuate the excessive dose exposure to the surrounding brain in a large BM due to the GTV shrinkage during multi-fraction SRS.

Intra-arterial chemoradiotherapy for oral cancer: Superiority of intensity-modulated radiation therapy over three-dimensional conformal radiation therapy.

PURPOSE: To determine the superiority of intensity-modulated radiation therapy (IMRT) over three-dimensional conformal radiation therapy (3DCRT) in patients who underwent intra-arterial chemoradiotherapy for oral cancer. METHODS: We retrospectively analyzed patients with locally advanced oral cancer curatively treated with intra-arterial chemoradiotherapy at a single institution between 2010 and 2021. All patients treated after May 2015 underwent IMRT. Docetaxel (12 mg/m2/week) and nedaplatin (5 mg/m2/day) were administered through a shallow temporal artery using a catheter. RESULTS: In total, 143 patients (IMRT: 71; 3DCRT: 72) were included in this study. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 75.7 % and 59.8 %, respectively, with no significant differences between the irradiation methods. In multivariate analysis, cervical lymph node metastasis (LNM) was the only significant poor prognostic factor contributing to OS, PFS, locoregional control (LRC), and local control (LC). In multivariate subgroup analysis of LNM cases (n = 90), IMRT contributed to favorable LRC (hazard ratio [HR]=0.4, P = 0.01) and LC (HR=0.4, P = 0.006). There was no difference in the incidence of grade ≥2 osteonecrosis of the jaw (4.2 % vs. 12.5 %, P = 0.13), xerostomia (75 % vs. 82 %, P = 0.316), or dysgeusia (80 % vs. 82 %, P = 0.834) between the IMRT and 3DCRT groups. However, the rates of xerostomia at 6 months and dysgeusia at 3 months were lower in the IMRT group (both P < 0.001). CONCLUSION: IMRT neither improved patient survival nor significantly reduced the incidence of osteonecrosis of the jaw. However, it demonstrated favorable LRC and LC in patients with LNM, suggesting an advantage in early recovery from xerostomia and dysgeusia.

Appropriateness of Dose Attenuation Margin Outside the Gross Tumor Volume (GTV) in Volumetric-Modulated Arc-Based Radiosurgery for Brain Metastasis With the Steepest Dose Gradient Outside the GTV and Biologically Effective Dose 80 Gy to GTV Boundary.

Introduction In stereotactic radiosurgery (SRS) for brain metastasis (BM), volumetric-modulated arcs (VMA) can provide a suitable dose distribution and efficient delivery, even with a widely available 5-mm leaf-width multileaf collimator (MLC). The planning optimization with affirmatively accepting internal high doses of a gross tumor volume (GTV) enhances the steepness of the dose gradient outside the GTV. However, an excessively steep dose falloff outside a GTV is susceptible to insufficient coverage of inherent irradiation uncertainties with the dose attenuation margin. This study was conducted to examine the appropriateness of dose attenuation margin outside a GTV in 5-mm MLC VMA-based SRS with a steep dose gradient and dose prescription with a biologically effective dose (BED) 80 Gy in various fractions to the GTV margin. Materials and methods This was a planning study for the clinical scenario of a single BM and targeted 28 GTVs, including nine sphere-shaped models with diameters of 5-45 mm and 19 clinical BMs (GTV 0.08-44.33 cc). SRS plans were generated for each GTV using 5-mm MLC VMA with an optimization that prioritized the steepness of dose falloff outside the GTV boundary without any internal dose constraints. A prescribed dose with the BED 80 Gy in 1-10 fraction(s) was assigned to the GTV D V-0.01 cc, a minimum dose of GTV minus 0.01 cc (D >95% for GTV >0.20 cc, D 95% for GTV ≤0.20 cc). The BED was based on the linear-quadratic formula with an alpha/beta ratio of 10 (BED10). Two planning systems were compared for the GTV + 2 mm structures that were generated by adding an isotropic 2-mm margin to the GTV. Results The GTV + 2 mm volumes differed significantly between the systems and further varied on the dose-volume histograms. The D V-0.05 cc, D 98%, and D 95% of the GTV + 2 mm were associated with substantial over- or under-coverages of the GTV + 2 mm, although the irradiated isodose volumes (IIVs) of the D 98% were closest to the GTV + 2 mm in general. The coverage values of the GTV + 2 mm with the minimum dose of the IIV equivalent to the GTV + 2 mm, D eIIV, were 93.3%-98.7% (≥95% in 26 cases). The GTV + 2 mm D eIIV relative to the GTV D V-0.01 cc was ≥81.9% (BED10 ≥60 Gy in ≤5 fractions) in 13 cases, while those were <69.8% (BED10 <48 Gy in ≤5 fractions) in four cases with the GTV of 0.33-1.77 cc. Conclusions A dose attenuation margin outside a GTV can be excessively steep for some small GTVs in 5-mm MLC VMA-based SRS with a steepest dose gradient and a BED10 80 Gy in ≤5 fractions to the GTV D V-0.01 cc, for which an adjustment of the too precipitous dose gradient is preferred to sufficiently cover relevant uncertainties. A GTV + 2 mm D eIIV with ≥95% coverage is more suitable for evaluating the appropriateness of dose attenuation outside the GTV than other common metrics with a fixed % coverage or D V-≤0.05 cc. Given the substantial variability in margin addition functions among planning systems, dose prescription to a margin-added GTV is unsuitable for ensuring uniform dose prescription.

Clinical characteristics and pathological features of undetectable clinically significant prostate cancer on multiparametric magnetic resonance imaging: A single-center and retrospective study.

Objectives: The objectives of this study were to clarify the pathological features of clinically significant prostate cancer (csPC) that is undetectable on multiparametric magnetic resonance imaging (mpMRI). Material and Methods: This single-center and retrospective study enrolled 33 men with prostate cancer (PC), encompassing 109 PC lesions, who underwent mpMRI before radical prostatectomy. Two radiologists independently assessed the mpMR images of all lesions and compared them with the pathological findings of PC. All PC lesions were marked on resected specimens using prostate imaging reporting and data system version 2.1 and classified into magnetic resonance imaging (MRI)-detectable and MRI-undetectable PC lesions. Each lesion was classified into csPC and clinically insignificant PC. Pathological characteristics were compared between MRI-detectable and MRI-undetectable csPC. Statistical analysis was performed to identify factors associated with MRI detectability. A logistic regression model was used to determine the factors associated with MRI-detectable and MRI-undetectable csPC. Results: Among 109 PC lesions, MRI-detectable and MRI-undetectable PCs accounted for 31% (34/109) and 69% (75/109) of lesions, respectively. All MRI-detectable PCs were csPC. MRI-undetectable PCs included 30 cases of csPC (40%). The detectability of csPC on mpMRI was 53% (34/64). The MRI-undetectable csPC group had a shorter major diameter (10.6 ± 6.6 mm vs. 19.0 ± 6.9 mm, P < 0.001), shorter minor diameter (5.7 ± 2.9 mm vs. 10.7 ± 3.4 mm, P < 0.001), and lower percentage of lesions with Gleason pattern 5 (17% vs. 71%, P < 0.001). Shorter minor diameter (odds ratio [OR], 2.62; P = 0.04) and lower percentage of Gleason pattern 5 (OR, 24; P = 0.01) were independent predictors of MRI-undetectable csPC. Conclusion: The pathological features of MRI-undetectable csPC included shorter minor diameter and lower percentage of Gleason pattern 5. csPC with shorter minor diameter may not be detected on mpMRI. Some MRI-undetectable csPC lesions exhibited sufficient size and Gleason pattern 5, emphasizing the need for further understanding of pathological factors contributing to MRI detectability.

Deep Learning-based Lung dose Prediction Using Chest X-ray Images in Non-small Cell Lung Cancer Radiotherapy.

Purpose: This study aimed to develop a deep learning model for the prediction of V20 (the volume of the lung parenchyma that received ≥20 Gy) during intensity-modulated radiation therapy using chest X-ray images. Methods: The study utilized 91 chest X-ray images of patients with lung cancer acquired routinely during the admission workup. The prescription dose for the planning target volume was 60 Gy in 30 fractions. A convolutional neural network-based regression model was developed to predict V20. To evaluate model performance, the coefficient of determination (R2), root mean square error (RMSE), and mean absolute error (MAE) were calculated with conducting a four-fold cross-validation method. The patient characteristics of the eligible data were treatment period (2018-2022) and V20 (19.3%; 4.9%-30.7%). Results: The predictive results of the developed model for V20 were 0.16, 5.4%, and 4.5% for the R2, RMSE, and MAE, respectively. The median error was -1.8% (range, -13.0% to 9.2%). The Pearson correlation coefficient between the calculated and predicted V20 values was 0.40. As a binary classifier with V20 <20%, the model showed a sensitivity of 75.0%, specificity of 82.6%, diagnostic accuracy of 80.6%, and area under the receiver operator characteristic curve of 0.79. Conclusions: The proposed deep learning chest X-ray model can predict V20 and play an important role in the early determination of patient treatment strategies.

A case of uterine adenomyoma of endocervical type that was suspected as minimal deviation adenocarcinoma on biopsy, MRI findings, and literature review.

Uterine adenomyomas of endocervical type are rare benign tumors of the uterine cervix commonly presented as cyst-like, dilated glandular structures within polypoid masses. A premenopausal woman in her 50s was referred to our hospital because of an increasing watery vaginal discharge. A multifocal cyst measuring 5 × 4.5 cm in size projecting into the endocervical canal was revealed on a contrast-enhanced MRI. The fluid within the tumor showed a hypointense signal on T1-weighted imaging (T1WI) and a hyperintense signal on T2-weighted imaging (T2WI). On T2WI, most of the septa within the tumor showed a slightly hyperintense to hypointense signal, whereas some areas revealed a strong hypointense signal; the contrast effect on the septum was satisfactory. On the T2WI taken 2 years previously, the tumor was a 4.5 × 3.5 cm polypoid mass protruding from the posterior endocervical wall. Contrastingly, the current T2WI showed that the stem was no longer identifiable because of tumor growth. Because previous imaging showed that the tumor was a stalked tumor protruding from the posterior endocervical wall, the imaging diagnosis was uterine adenomyoma of the endocervical type. A biopsy suggested the possibility of a minimal deviation adenocarcinoma (MDA). Hence, a total hysterectomy was performed. The final diagnosis confirmed the uterine adenomyoma of endocervical type. Uterine adenomyoma of the endocervical type might be difficult to differentiate from MDA in small biopsy specimens; therefore, evaluation of morphology by MRI is considered important in preoperative diagnosis.

Proposal of an Alternative Near-Minimum Isodose Surface DV-0.01 cc Equally Minimizing Gross Tumor Volume Below the Relevant Dose as the Basis for Dose Prescription and Evaluation of Stereotactic Radiosurgery for Brain Metastases.

Introduction In stereotactic radiosurgery (SRS) for brain metastasis (BM), the prescribed dose is generally reported as a minimum dose to cover a specific percentage (e.g. D98%) of the gross tumor volume (GTV) with or without a margin or an unspecified intended marginal dose to the GTV boundary. In dose prescription to a margin-added planning target volume (PTV), the GTV marginal dose is likely variable and unclear. This study aimed to reveal major flaws of dose prescription to a fixed % coverage of a target volume (TV), such as GTV D98% or PTV D95%, and to propose an alternative. Materials and methods Seven quasi-spherical models with volumes ranging from 1.00 to 15.00 cc were assumed as GTVs. The GTVs and the volumes generated by adding isotropic 1- and 2-mm margins to the GTV boundaries (GTV + 1 and 2 mm) were used for SRS planning, dose prescription, and evaluation. Volumetric-modulated arcs with a 5-mm leaf-width multileaf collimator were used to optimize each SRS plan to ensure the steepest dose gradient outside each TV boundary. In dose prescription to the GTV D98%, 0.02-0.3 cc of the GTV is below the prescribed dose, and the volume increases with larger GTVs. The volume below the prescribed dose should be less than the equivalent of a 3-mm-diameter lesion, i.e. 0.01 cc. Therefore, DV-0.01 cc was defined as an alternative near-minimum dose for which the TV below a relevant dose is less than 0.01 cc. Four different dose prescriptions, including the GTV DV-0.01 cc, were compared using specific doses in 1, 3, and 5 fractions, equivalent to 80, 60, and 50 Gy, respectively, as biologically effective doses (BEDs) to the boundaries of GTV, GTV + 1 mm, and GTV + 2 mm, respectively. Results Dose prescription to the GTV DV-0.01 cc corresponds to 95.0, 98.0, and 99.0-99.93% coverages for the GTV of 0.20, 0.50, and 1.00-15.00 cc, respectively. The GTV DV-0.01 cc varied substantially and decreased significantly as the GTV increased in dose prescriptions to the GTV D98%, GTV + 1 mm D95%, and GTV + 2 mm D95%. The GTV + 2 mm DV-0.01 cc increased significantly as the GTV increased, except for the dose prescription to the GTV + 2 mm D95% with a decreasing tendency. When comparing BED-based specific dose prescriptions, dose prescription to the GTV DV-0.01 cc was optimal in terms of the following: 1) consistency of the near-minimum dose of GTV; 2) the highest BED at 2 mm outside the GTV, except for 1.00 cc GTV, and the rational increase with increasing GTV; and 3) the highest BED at 2 mm inside the GTV. In dose prescription with the BED of 80 Gy in 1 fraction and 5 fractions to the GTV DV-0.01 cc, the GTV limits were ≤1.40 and ≤8.46 cc, respectively, in order for the irradiated isodose volume not to exceed the proposed thresholds for minimizing the risk of brain radionecrosis. Conclusions Dose prescription to a fixed % coverage of a GTV with or without a margin leads to the substantially varied near-minimum dose at the GTV boundary, which significantly decreases with increasing GTV. Alternatively, GTV DV-0.01 cc with a variable coverage (D>95%) for >0.20 cc GTV and fixed D95% for ≤0.20 cc GTV is recommended as the basis for dose prescription and evaluation, along with supplemental evaluation of the marginal dose of the GTV plus a margin (e.g. GTV + 2 mm) to demonstrate the appropriateness of dose attenuation outside the GTV boundary.

The Guidelines for Percutaneous Transhepatic Portal Vein Embolization: English Version.

Preoperative portal vein embolization is a beneficial option to reduce the risk of postoperative liver failure by promoting the growth of the future liver remnant. In particular, a percutaneous transhepatic procedure (percutaneous transhepatic portal vein embolization) has been developed as a less-invasive approach. Although percutaneous transhepatic portal vein embolization is widely recognized as a safe procedure, various complications, including rare but fatal adverse events, have been reported. Currently, there are no prospective clinical trials regarding percutaneous transhepatic portal vein embolization procedures and no standard guidelines for the PTPE procedure in Japan. As a result, various methods and various embolic materials are used in each hospital according to each physician's policy. The purpose of these guidelines is to propose appropriate techniques at present and to identify issues that should be addressed in the future for safer and more reliable percutaneous transhepatic portal vein embolization techniques.

Solid tumours showing oligoprogression to immune checkpoint inhibitors have the potential for abscopal effects.

PURPOSE: Given the uncertainty surrounding the abscopal effect (AE), it is imperative to identify promising treatment targets. In this study, we aimed to explore the incidence of AE when administering radiotherapy to patients with oligoprogressive solid tumours while they are undergoing treatment with immune checkpoint inhibitors (ICIs). MATERIALS AND METHODS: In this multicentre prospective observational study, oligoprogressive disease was defined as a < 20% increase in lesions compared to > 2 months before enrolment. We enrolled patients who requested radiotherapy during the ICI rest period between 2020 and 2023. AE was considered present if ≥ 1 non-irradiated lesion decreased by ≥ 30% before the next line of systemic therapy started. RESULTS: Twelve patients were included in this study; the common primary lesions were in the lungs (four patients) and kidneys (three patients). AEs were observed in six (50%) patients, with a median time to onset of 4 (range 2-9) months after radiotherapy. No significant predictors of AEs were identified. Patients in the AE group had a significantly better 1-year progression-free survival (PFS) rate than those in the non-AE group (p = 0.008). Two patients from the AE group were untreated and progression-free at the last follow-up. Four (33%) patients experienced grade 2 toxicity, with two cases attributed to radiotherapy and the other two to ICI treatment. No grade 3 or higher toxicities were observed in any category. CONCLUSION: Patients with oligoprogressive disease may be promising targets with potential for AEs. AEs can lead to improved PFS and, in rare cases, to a certain progression-free period without treatment. Irradiating solid tumours in patients with oligoprogressive disease during immune checkpoint inhibitor therapy may be a promising target with the potential for abscopal effects (AEs). AEs can lead to improved progression-free survival and, in rare cases, to a certain progression-free period without treatment.

Primary renal neuroendocrine tumor: A case report with computed tomography findings.

We report a rare case of a primary renal neuroendocrine tumor. The patient was a 64-year-old woman. The patient's chief complaint was gross hematuria. Dynamic contrast-enhanced computed tomography (CT) revealed a hypovascular mass 13 cm in diameter in the right kidney. The border of the mass was clear. A grossly contrast-impaired area and internal granular calcification were observed. A right radical nephrectomy was performed. Macroscopically, the mass was hemorrhaged and necrotic. It was diagnosed as a neuroendocrine tumor (NET) (Grade 2) histologically. Findings, such as hypovascularity, calcification, and necrosis, in our case were similar to those in previous reports. These findings are considered relatively characteristic of primary renal NETs.

Evaluation of virtual monochromatic imaging with dual-energy computed tomography of small liver metastases from malignant abdominal tumours: Quantitative and qualitative analyses.

Background: The assessment of small metastatic liver tumours using dual-energy computed tomography (DECT) has not been fully established. Purpose: To assess the effect of low-keV virtual monochromatic imaging (VMI) with non-contrast and contrast-enhanced DECT on the qualitative and quantitative image parameters of small liver metastases. Material and methods: Two radiologists retrospectively evaluated 92 metastatic liver tumours (5-20 mm) in 32 patients. Non-contrast and contrast-enhanced VMI were reconstructed at seven energy levels (40-100 keV) with 10-keV intervals. Lesion boundary, lesion delineation, image noise, and overall image quality were evaluated using the visual analogue scale. A high subjective score indicates good overall image quality, clear nodal boundaries and delineation, and less noticeable image noise. Subjective scores were compared using the Kruskal-Wallis test. A quantitative analysis involving the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) was performed. Results: The lesion boundary was highest at 40 keV and significantly improved during the non-contrast portal venous phase compared to that at higher keV (p < .005). The lesion delineation score was significantly higher at 40 keV and tended to decrease at higher keV. Image noise and overall image quality were rated low at low keV; however, those at 80, 90, and 100 keV were rated the highest (p < .005). The CNR and SNR were highest for non-contrast CT at 100 keV. During the portal venous phase, no significant differences were observed in CNR and SNR at each keV. Conclusion: Low-keV imaging using non-contrast and contrast-enhanced DECT is useful for delineating small hepatic metastatic tumours.

Five-Fraction Radiosurgery Using a Biologically Equivalent Dose of a Single Fraction of 24 Gy for a 3-cm Parasagittal Para-Central Sulcus Brain Metastasis From Adenocarcinoma of the Cecum.

An isolated single brain metastasis (BM) is an extremely rare manifestation of failure in patients with cecal adenocarcinoma (CAC). Total en bloc resection (while preserving function) of a 3-cm BM involving both the primary motor and sensory cortexes presents a conundrum: achieving long-term local control and safety of such a BM is also challenging for stereotactic radiosurgery (SRS). We describe the case of a 3.1-cm BM from CAC in the left parasagittal para-central sulcus region, which was treated using five-fraction SRS with a biologically effective dose (BED) of 81.6 Gy. In the SRS, the gross tumor volume (GTV, 7.14 cm3) was defined based on computed tomography (CT)/T1/T2 matching (enhancing lesion 11.66 cm3), and 98.7% of the GTV (CT/T2 mass) was covered with 43.6 Gy (58% isodose) using volumetric-modulated arcs. The maximum tumor response was partial (19.7% of the prior GTV) and sustained for 15.2 months, leaving minor neurological symptoms. However, the patient developed neurological worsening at six months, attributed to adverse radiation effects with a CT/T1/T2 mismatch, for which medical management, including the addition of bevacizumab (BEV), was effective for one year. Multi-fraction SRS with a high marginal and internal BED and sequential systemic therapy, including BEV, can be a minimally invasive, efficacious, and durable treatment option for a large CAC-BM involving the central sulcus. Early co-administration of BEV following SRS, dose escalation to the GTV boundary, and more than five fractions of SRS may be considered to improve the efficacy and safety further.

Nineteen-Month Immunity to Adverse Radiation Effects Following 5-Fraction Re-radiosurgery With 43.6 Gy for Local Progression After Prior 3-Fraction Radiosurgery for Brain Metastasis From Pan-Negative Lung Adenocarcinoma.

Clinical management of patients with local control failure following stereotactic radiosurgery (SRS) for brain metastasis (BM) can be frequently challenging. Re-irradiation with multi-fraction (fr) SRS by using a biological effective dose of ≥80 Gy, based on the linear-quadratic formula with an alpha/beta ratio of 10 (BED10), can be an efficacious option for such a scenario with the BED10 of <80 Gy. However, its long-term safety beyond one year remains unclear. In this report, we describe the case of a patient with a single metachronous BM from lung adenocarcinoma (LAC), without major genetic alterations, in which re-SRS with 43.6 Gy/5 fr (BED10 81.6 Gy) for local progression, following prior 3-fr SRS of the BM, resulted in sustained regression without any local adverse radiation effects (AREs) for 19 months. The BM with a gross tumor volume (GTV) of 1.12 cm3 in the left parietal lobe was initially treated with SRS of 27 Gy/3 fr (50% isodose). Despite steroid administration for nivolumab-induced bullous pemphigoid associated with transient elevation of tumor markers, the BM showed local progression with T1/T2 matching at 38.3 and eight months after SRS and discontinuation of nivolumab, respectively. In the 5-fr re-SRS, 99% of the GTV (1.18 cm3) was covered with 43.6 Gy (63% isodose). However, along with the thoracic disease progression, multiple new BMs developed 15.5 months after the re-SRS, for which volumetric-modulated arc-based whole brain radiotherapy (WBRT) was administered, with simultaneously integrated boosts to 17 lesions and moderate dose attenuation in the pre-irradiated region. However, concurrent administration of gemcitabine and WBRT might have led to persistent severe anorexia for 2.5 months. The patient died 10.8 years after the initial chemotherapy. The relatively small GTV with the superficial location may have rendered the re-irradiated region immune to AREs after the high BED10 re-SRS. Long-term survival can be achieved by chemoimmunotherapy in patients with pan-negative LAC, with limited systemic metastases who are unfit for targeted agents. Therefore, SRS for limited BMs in such scenarios should aim for complete local tumor eradication beyond a partial response in either a first-line or re-irradiation setting.

Volumetric-Modulated Arc-Based Re-radiosurgery With Simultaneous Reduced-Dose Whole-Brain Irradiation for Local Failures Following Prior Radiosurgery of Brain Oligometastases From Small Cell Lung Cancer.

First-line and possibly repeated stereotactic radiosurgery (SRS) with preserving whole-brain radiotherapy (WBRT) is an attractive and promising option for synchronous or metachronous limited brain metastases (BMs) from small cell lung cancer (SCLC), for which a modest prescription dose is generally preferred, such as a biological effective dose of ≤60 Gy, based on the linear-quadratic formula with an alpha/beta ratio of 10 (BED10). In addition, the optimal planning scheme for re-SRS for local progression after SRS of BMs from SCLC remains unclear. Herein, we describe a case of limited BMs developing after a partial response to standard chemoradiotherapy (CRT) for limited-stage SCLC. The BMs, including local failures following prior single-fraction (fr) SRS, were re-treated with volumetric-modulated arc-based SRS combined with simultaneous reduced-dose WBRT. The first SRS with 36.3 Gy/3 fr (BED10 80 Gy) for a small BM resulted in a local control of 17.2 months. However, the second SRS with 20 Gy/1 fr (BED10 60 Gy) to the 60% or 85% isodose surface (IDS) covering the gross tumor volume (GTV) of three new BMs with a paradoxical T1/T2 mismatch, that is, a visible mass on T2 larger than an enhancing area, resulted in partial symptomatic local progression of all lesions within 5.2 months, along with the development of two new lesions, despite continued amrubicin monotherapy. In contrast, the third SRS with 53 Gy/10 fr (BED10 81 Gy) to ≤74% IDSs encompassing the GTV boundary resulted in complete responses of all the lesions during six months. However, despite a combined use of WBRT of 25 Gy in the third SRS, symptomatic spinal cerebrospinal fluid dissemination and new BMs developed, the former leading to patient mortality. A BED10 of ≥80 Gy to the GTV margin and a steep dose increase inside the GTV boundary are suitable to ensure excellent local control in SRS for SCLC BMs. Re-SRS with the aforementioned scheme can be an efficacious option for local failures following prior SRS with a BED10 of ≤60 Gy. Modest dose escalation with a simultaneous integrated boost to bulky lesions in the initial CRT may reduce the development of new BM through improved control of the potential source.

Twenty-Month Regression Following Concurrent Conventional Whole-Brain Irradiation and Chemoimmunotherapy for ≥3.8 cm Cerebellar Metastasis From Small Cell Lung Cancer.

Standard whole-brain radiotherapy (WBRT) alone for large brain metastases (BMs) from small cell lung cancer (SCLC) has limited efficacy and durability, and stereotactic radiosurgery (SRS) alone for symptomatic posterior fossa BMs >3 cm with satellite lesions is challenging. Herein, we describe the case of a 73-year-old female presenting with treatment-naïve SCLC and 15 symptomatic multiple BMs, including a ≥3.8-cm cerebellar mass (≥17.7 cm3) and two adjacent lesions; otherwise, the SCLC was confined to the thorax. The patient was initially treated concurrently with conventional WBRT (30 Gy in 10 fractions) without boost and chemoimmunotherapy (CIT) consisting of carboplatin, etoposide, and atezolizumab. Atezolizumab was excluded during irradiation. Five months after WBRT, the large cerebellar lesion had remarkably regressed, and the smaller lesions (≤17 mm) showed complete responses (CRs) without local progression at 20 months. However, six and 16 months after WBRT, the thoracic lesions had progressed, and although amrubicin was administered, four new BMs, including pons involvement, had developed, respectively. Despite the CRs of the four BMs following SRS (49.6 Gy in eight fractions) and the sustained regression of the thoracic lesions, meningeal dissemination and multiple new BMs were evident 3.5 months post-SRS. The small remnant of the large BM and/or newly developed BMs abutting the cerebrospinal fluid (CSF) space could have led to CSF dissemination, the presumed cause of the patient's death. Taken together, concurrent chemo-WBRT and subsequent CIT can provide excellent and durable tumor responses for SCLC BMs, but may not be fully sufficient for BMs ≥3.8 cm. Therefore, in cases with large lesions, focal dose escalation of the large lesions, consolidative thoracic radiotherapy, and dose de-escalation in the macroscopically unaffected brain region may prevent or attenuate CSF dissemination, new BM development, and adverse effects and thus should be considered.

In Vitro Characterization of Drug-Loaded Superabsorbent Polymer Microspheres: Absorption and Release Capacity of Contrast Material, Antibiotics and Analgesics.

PURPOSE: To examine the characteristics of drug-loaded superabsorbent polymer microspheres (SAP-MS) such as drug absorption, drug release, diameter, and visibility. MATERIALS AND METHODS: SAP-MS (HepaSphere150-200 µm; Merit Medical, South Jordan, UT, USA) were suspended in drug solutions: (a) cefazolin, (b) lidocaine, (c) iopamidol and cefazolin, (d) iopamidol and lidocaine, and (e) iopamidol, cefazolin, and lidocaine. The concentrations of drugs were measured, and the amount of each drug absorbed was calculated. Filtered drug-loaded SAP-MS were mixed with saline, and the drug release rates were calculated. The diameter changes of SAP-MS during absorption were observed. Radiography of drug-loaded SAP-MS was evaluated as radiopacity by contrast-to-noise ratio (CNR). RESULTS: The drug concentration did not change during absorption. The release rates increased for 10 min and then came to an equilibrium. The mean amounts of drug absorbed at 180 min and mean release rates at 24 h were (a) cefazolin: 265.4 mg, 64.2%; (b) lidocaine: 19.6 mg, 75.6%; (c) iopamidol: 830.2 mg, 22.5%; cefazolin: 137.6 mg, 21.2%; (d) iopamidol: 1620.6 mg, 78.5%; lidocaine: 13.5 mg, 81.4%; and (e) iopamidol: 643.7 mg, 52.9%; cefazolin: 194.0 mg, 51.6%; lidocaine: 5.3 mg, 58.4%. The diameter of SAP-MS increased for approximately 15 min. Finally, the diameters of SAP-MS were (a) 3.9 times, (b) 5.0 times, (c) 2.2 times, (d) 5.5 times, and (e) 3.6 times larger than the original size. Drug-loaded SAP-MS containing iopamidol were visible under X-ray imaging, with CNRs of (c) 3.0, (d) 9.0, and (e) 4.5. CONCLUSION: SAP-MS can absorb and release iopamidol, cefazolin, and lidocaine.

5-Fraction Re-radiosurgery for Progression Following 8-Fraction Radiosurgery of Brain Metastases From Lung Adenocarcinoma: Importance of Gross Tumor Coverage With Biologically Effective Dose ≥80 Gy and Internal Dose Increase.

The criteria for indication of salvage stereotactic radiosurgery (SRS) for local progression following multi-fraction (mf) SRS of brain metastases (BMs) remain controversial, along with the optimal planning scheme. Herein, we described a case of BMs from pan-negative lung adenocarcinoma (LAC), in which the two lesions of local progression following initial eight-fraction (8-fr) SRS were re-treated with 5-fr SRS with the biologically effective dose (BED10) of ≥80 Gy, based on the linear-quadratic (LQ) formula with an alpha/beta ratio of 10. The re-SRS resulted in the alleviation of symptoms and favorable tumor responses with minimal adverse effects during the 7.3-month follow-up. In the lesions of local progression, the gross tumor volume (GTV) coverage with 49.6 Gy (BED10 80 Gy) was generally insufficient, and the GTV dose wes relatively homogeneous with ≥87% isodose covering. In contrast, the 5-fr re-SRS was performed with sufficient GTV coverage with ≤68% isodose of 43 Gy (BED10 80 Gy). Taken together, sufficient GTV coverage with a BED10 of ≥80 Gy and steep dose increase inside the GTV boundary, that is, extremely inhomogeneous GTV dose, are important in 8-fr SRS for ensuring excellent local control of BMs from pan-negative LAC. For local progression following mfSRS that does not fulfill both criteria, re-SRS with the above planning scheme can be an efficacious and safe treatment option for at least six months, especially in cases in which the prior SRS was performed with a dose/fractionation under adequate consideration of brain tolerance. The BED10 seems to be the most suitable for estimating the anti-tumor efficacies of SRS doses in 3-8 fr, similar to that of a single fraction of 24 Gy.