Autologous Peripheral Blood Stem Cell Transplantation and Timing of Local Radiation Therapy in Patients With Malignant Lymphoma: Results of the Japanese Radiation Oncology Study Group Questionnaire Survey.

BACKGROUND/AIM: Malignant lymphoma (ML) including Hodgkin's lymphoma and non-Hodgkin's lymphoma is often treated with local radiation therapy (RT) in combination with autologous hematopoietic stem cell transplantation (ASCT) to prevent relapse; however, the efficacy and optimal timing of this approach is unclear. In this study, a national survey conducted by the Japanese Radiation Oncology Study Group reviewed ML cases from 2011 to 2019 to determine whether RT should be added to ASCT, focusing on the use of autologous peripheral blood stem cell transplantation (auto-PBSCT), a predominant form of ASCT. PATIENTS AND METHODS: The survey encompassed 92 patients from 11 institutes, and assessed histological ML types, treatment regimens, timing of RT relative to auto-PBSCT, and associated adverse events. RESULTS: The results indicated no significant differences in adverse events, including myelosuppression, based on the timing of RT in relation to auto-PBSCT. However, anemia was more prevalent when RT was administered before auto-PBSCT, and there was a higher incidence of neutropenia recovery delay in patients receiving RT after auto-PBSCT. CONCLUSION: This study provides valuable insights into the variable practices of auto-PBSCT and local RT in ML treatment, emphasizing the need for optimized timing of these therapies to improve patient outcomes and reduce complications.

FLASH Effect Is Not Always Induced by Ultra-high Dose-rate Proton Irradiation Under Hypoxic Conditions.

BACKGROUND/AIM: Pre-clinical studies have shown that irradiation with electrons at an ultra-high dose-rate (FLASH) spares normal tissue while maintaining tumor control. However, most in vitro experiments with protons have been conducted using a non-clinical irradiation system in normoxia alone. This study evaluated the biological response of non-tumor and tumor cells at different oxygen concentrations irradiated with ultra-high dose-rate protons using a clinical system and compared it with the conventional dose rate (CONV). MATERIALS AND METHODS: Non-tumor cells (V79) and tumor cells (U-251 and A549) were irradiated with 230 MeV protons at a dose rate of >50 Gy/s or 0.1 Gy/s under normoxic or hypoxic (<2%) conditions. The surviving fraction was analyzed using a clonogenic cell survival assay. RESULTS: No significant difference in the survival of non-tumor or tumor cells irradiated with FLASH was observed under normoxia or hypoxia compared to the CONV. CONCLUSION: Proton irradiation at a dose rate above 40 Gy/s, the FLASH dose rate, did not induce a sparing effect on either non-tumor or tumor cells under the conditions examined. Further studies are required on the influence of various factors on cell survival after FLASH irradiation.

Poly(ester imide)s with Low Linear Coefficients of Thermal Expansion and Low Water Uptake (VII): A Strategy to Achieve Ultra-Low Dissipation Factors at 10 GHz.

In this study, a series of ester-linked tetracarboxylic dianhydrides (TCDAs) with 2,6-naphthalene-containing longitudinally extended structures consisting of different numbers of aromatic rings (NAr = 6-8) was synthesized to obtain novel modified polyimides, poly(ester imide)s (PEsIs). These TCDAs were fully compatible with the conventional manufacturing processes of conventional polyimide (PI) systems. As an example, the PEsI film obtained from the ester-linked TCDA (NAr = 8) and an ester-linked diamine achieved unprecedented outstanding dielectric properties without the support of fluorinated monomers, specifically an ultra-low dissipation factor (tan δ) of 0.00128 at a frequency of 10 GHz (50% RH and 23 °C), in addition to an extremely high glass transition temperature (Tg) of 365 °C, extremely low linear coefficient of thermal expansion (CTE) of 6.8 ppm K-1, suppressed water uptake (0.24%), requisite film ductility, and a low haze. Consequently, certain PEsI films developed in this study are promising candidates for heat-resistant dielectric substrates for use in 5G-compatible high-speed flexible printed circuit boards (FPCs). The chemical and physical factors denominating tan δ are also discussed.

Clinical Results and Hematologic Predictors of Linear Accelerator-Based Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy for Brain Metastasis in Patients Aged 75 Years or Older: A Retrospective Study.

OBJECTIVE: This study aimed to evaluate prognostic factors including pre-radiosurgical blood count in elderly patients (EPs) with brain metastasis (BM) who were treated using linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator. METHODS: Between January 2011 and November 2021, 101 consecutive EPs with BM were treated by LINAC-based SRS or fSRT using LINAC with a micro-multileaf collimator. EPs were defined as patients aged ≥75 years. RESULTS: The tumors originated from the lungs (n = 90; 89.1%), colon (n = 2; 2.0%), and others (n = 9; 8.8%) in these EPs. The median pretreatment Karnofsky Performance Status was 80 (range, 40-100). The median follow-up time was 10 months (range, 0-76), as was the median survival. The 6-month, 1-year, and 2-year survival in the EP group was 58.3%, 43.2%, and 28.5%, respectively. Freedom from local failure at 6 months and 1 and 2 years was 97%, 95%, and 91.5%, respectively. Freedom from distant failure at 6 months and 1 and 2 years in EPs was 70.6%, 59.4%, and 54.2%, respectively. A high neutrophil/lymphocyte ratio >5.33 was an unfavorable predictor of prognosis for EPs with BMs treated with SRS and fSRT (P < 0.001). In the EPs, the prognostic factors associated with prolonged survival in the Cox proportional hazards model were being female and a good pretreatment Karnofsky Performance Status. CONCLUSIONS: The findings of our study highlight the efficacy of LINAC-based SRS and fSRT with a micro-multileaf collimator in the treatment of EPs with BMs. Neutrophil/lymphocyte ratio can be an important factor in treatment decisions for EPs with BMs.

Colorless Polyimides Derived from 5,5'-bis(2,3-norbornanedicarboxylic anhydride): Strategies to Reduce the Linear Coefficients of Thermal Expansion and Improve the Film Toughness.

In this paper, novel colorless polyimides (PIs) derived from 5,5'-bis(2,3-norbornanedicarboxylic anhydride) (BNBDA) were presented. The results of single-crystal X-ray structural analysis using a BNBDA-based model compound suggested that it had a unique steric structure with high structural linearity. Therefore, BNBDA is expected to afford new colorless PI films with an extremely high glass transition temperature (Tg) and a low linear coefficient of thermal expansion (CTE) when combined with aromatic diamines with rigid and linear structures (typically, 2,2'-bis(trifluoromethyl)benzidine (TFMB)). However, the polyaddition of BNBDA and TFMB did not form a PI precursor with a sufficiently high molecular weight; consequently, the formation of a flexible, free-standing PI film via the two-step process was inhibited because of its brittleness. One-pot polycondensation was also unsuccessful in this system because of precipitation during the reaction, probably owing to the poor solubility of the initially yielded BNBDA/TFMB imide oligomers. The combinations of (1) the structural modification of the BNBDA/TFMB system, (2) the application of a modified one-pot process, in which the conditions of the temperature-rising profile, solvents, azeotropic agent, catalysts, and reactor were refined, and (3) the optimization of the film preparation conditions overcame the trade-off between low CTE and high film toughness and afforded unprecedented PI films with well-balanced properties, simultaneously achieving excellent optical transparency, extremely high Tg, sufficiently high thermal stability, low CTE, high toughness, relatively low water uptake, and excellent solution processability.

Quality of life in patients who underwent robot-assisted radical prostatectomy compared with those who underwent low-dose-rate brachytherapy.

BACKGROUND: To compare the quality of life (QOL) in patients who underwent robot-assisted radical prostatectomy (RARP) or low-dose-rate brachytherapy (LDR-BT) for prostate cancer. METHODS: We enrolled patients who underwent LDR-BT (LDR-BT alone [n = 540] or LDR-BT plus external beam radiation therapy [n = 428]) and RARP (n = 142). QOL was evaluated using the International Prostate Symptom Score, Expanded Prostate Cancer Index Composite (EPIC), Sexual Health Inventory for Men (SHIM), and 8-item Short Form (SF-8) health survey. The two groups were compared using propensity score matching analysis. RESULTS: At 24 months after treatment, the number of patients with worsened urinary QOL in the urinary domain of EPIC compared with baseline was 78/111 (70%) and 63/137 (46%) in the RARP and LDR-BT groups, respectively (p < 0.001). In the urinary incontinence and function domain, this number was higher in the RARP group versus the LDR-BT group. However, in the urinary irritative/obstructive domain, the number of patients with improved urinary QOL at 24 months compared with baseline was 18/111 (16%) and 9/137 (7%), respectively (p = 0.01). Regarding the SHIM score, sexual domain of EPIC, and mental component summary of SF-8, there were more number of patients with worsened QOL in the RARP group than in the LDR-BT group. In the EPIC bowel domain, the number of patients with worsened QOL was lower in the RARP group versus the LDR-BT group. CONCLUSION: The differences in QOL observed between patients treated with RARP and LDR-BT could assist in treatment selection for prostate cancer.

Long-Term Survival after Linac-Based Stereotactic Radiosurgery and Radiotherapy with a Micro-Multileaf Collimator for Brain Metastasis.

BACKGROUND: this study aimed to evaluate the prognostic factors associated with long-term survival after linear accelerator (linac)-based stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator for brain metastasis (BM). METHODS: This single-center retrospective study included 226 consecutive patients with BM who were treated with linac-based SRS or fSRT with a micro-multileaf collimator between January 2011 and December 2018. Long-term survival (LTS) was defined as survival for more than 2 years after SRS/fSRT. RESULTS: The tumors originated from the lung (n = 189, 83.6%), breast (n = 11, 4.9%), colon (n = 9, 4.0%), stomach (n = 4, 1.8%), kidney (n = 3, 1.3%), esophagus (n = 3, 1.3%), and other regions (n = 7, 3.1%). The median pretreatment Karnofsky performance scale (KPS) score was 90 (range: 40-100). The median follow-up time was 13 (range: 0-120) months. Out of the 226 patients, 72 (31.8%) were categorized in the LTS group. The median survival time was 43 months and 13 months in the LTS group and in the entire cohort, respectively. The 3-year, 4-year, and 5-year survival rate in the LTS group was 59.1%, 49.6%, and 40.7%, respectively. Multivariate regression logistic analysis showed that female sex, a pre-treatment KPS score ≥ 80, and the absence of extracranial metastasis were associated with long-term survival. CONCLUSIONS: female sex, a favorable pre-treatment KPS score, and the absence of extracranial metastasis were associated with long-term survival in the current cohort of patients with BM.

Late genitourinary and gastrointestinal toxicity and radiation-induced second primary cancers in patients treated with low-dose-rate brachytherapy.

OBJECTIVES: To evaluate late genitourinary (GU) and gastrointestinal (GI) toxicities and radiation-induced second primary cancers (RISPCs) in patients who received low-dose-rate brachytherapy (LDR-BT) with or without external beam radiotherapy for prostate cancer. METHODS: This retrospective study included 897 consecutive patients who received LDR-BT between July 2004 and July 2015 in our institution. Adverse events and the incidence of second primary cancers were evaluated at 1, 3, 6, 12, 18, 24, 30, 36, 48, 54, and 60 mo after LDR-BT and then once a year. Related factors to ≥grade 2 (G2) toxicity were evaluated using the Cox proportional-hazards model. RESULTS: The median follow-up time was 85.2 (interquartile range: 66.8-111.3) mo. The cumulative incidence rates of ≥G2 GU toxicity at 5 and 10 yrs after LDR-BT were 11.2% and 14.7%, respectively. The International Prostate Symptom Score before LDR-BT (continuous) (hazard ratio [HR]: 1.03), no neoadjuvant androgen deprivation therapy (HR: 1.69), and combination external beam radiotherapy (HR: 3.30) were risk factors related to the incidence of ≥G2 GU toxicity. The cumulative incidence rates of ≥G2 GI toxicity at 5 and 10 yrs after LDR-BT were 3.3% and 3.3%, respectively. Age (continuous) (HR: 1.09), body mass index (continuous) (HR: 0.87), and rectum V100 (continuous) (HR: 1.64) were risk factors related to ≥G2 GI toxicity. A total of 12 (1.3%) patients developed metachronous RISPCs (bladder cancer: 9; rectal cancer: 3). CONCLUSION: The incidence rates of late GU and GI toxicities and RISPCs after LDR-BT were low.

5-Aminolevulinic acid overcomes hypoxia-induced radiation resistance by enhancing mitochondrial reactive oxygen species production in prostate cancer cells.

BACKGROUND: The naturally occurring amino acid 5-aminolevulinic acid (5-ALA) is a precursor of protoporphyrin IX (PpIX) biosynthesised in the mitochondria. When accumulated PpIX is excited by light (wavelength of 625-635 nm), reactive oxygen species (ROS) are generated. Here, we investigated whether 5-ALA may increase the sensitisation of prostate cancer (PCA) cells to radiotherapy through the generation of ROS via its metabolite, PpIX. METHODS: Effect of 5-ALA on PC-3 and DU-145 PCA cell lines treated with ionising radiation (IR) was examined in vitro and in vivo with assessment by clonogenic assay, mitochondrial function and ROS production under normoxia or hypoxia condition. RESULTS: 5-ALA enhanced intra-mitochondrial ROS production immediately after exposure to IR and decreased mitochondrial membrane potential via increase of intra-cellular PpIX. IR with 5-ALA induced mitochondrial dysfunction and increased ATP production, switching energy metabolism to the quiescence. Under hypoxic condition, ROS burst and mitochondrial dysfunction were induced by IR with 5-ALA resulting reducing cancer stemness and radiation resistance. CONCLUSION: These results suggest that combined therapy with 5-ALA and radiation therapy is a novel strategy to improve the anti-cancer effects of radiation therapy for PCA.

Solution-Processable Colorless Polyimides Derived from Hydrogenated Pyromellitic Dianhydride: Strategies to Reduce the Coefficients of Thermal Expansion by Maximizing the Spontaneous Chain Orientation Behavior during Solution Casting.

In this study, practically useful colorless polyimides (PIs) with low coefficients of thermal expansion (CTEs) and other desirable properties were prepared from hydrogenated pyromellitic dianhydride (1-exo,2-exo,4-exo,5-exo-cyclohexanetetracarboxylic dianhydride, H-PMDA). A modified one-pot polymerization method afforded a high-molecular-weight PI with sufficient film-forming ability from 2,2'-bis(trifluoromethyl)benzidine (TFMB) with a rod-like structure and H-PMDA. However, the PI film cast from its homogeneous solution did not have low CTEs, similar to the analogous system using meta-tolidine. To solve this problem, a series of amide- and amide-imide-containing diamines were designed and synthesized. The modified one-pot polymerization of H-PMDA and the diamines in γ-butyrolactone produced homogeneous, viscous, and stable solutions of high-molecular-weight PIs with high solid contents. The cast films of certain systems examined in this study simultaneously achieved low CTEs, high optical transparency, considerably high glass transition temperatures (Tgs), and sufficient ductility. A possible mechanism for the generation of low CTEs, which is closely related to the spontaneous in-plane orientation behavior during solution casting, was proposed. Certain H-PMDA-based PIs developed in this study are promising colorless heat-resistant plastic substrates for use in image display devices and other optical applications.

Long-term outcomes and central nervous system relapse in extranodal natural killer/T-cell lymphoma.

To elucidate the long-term outcomes of non-anthracycline-containing therapies and central nervous system (CNS) events in patients with extranodal NK/T-cell lymphoma, nasal type (ENKTL), the clinical data of 313 patients with ENKTL diagnosed between 2000 and 2013 in a nationwide retrospective study in Japan were updated and analyzed. At a median follow-up of 8.4 years, the 5-year overall survival (OS) and progression-free survival (PFS) were 71% and 64%, respectively, in 140 localized ENKTL patients who received radiotherapy-dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) in clinical practice. Nine (6.4%) patients experienced second malignancies. In 155 localized ENKTL patients treated with RT-DeVIC, 10 (6.5%) experienced CNS relapse (median, 12.8 months after diagnosis). In five of them, the events were confined to the CNS. Nine of the 10 patients who experienced CNS relapse died within 1 year after CNS relapse. Multivariate analysis identified gingival (hazard ratio [HR], 54.35; 95% confidence interval [CI], 8.60-343.35) and paranasal involvement (HR, 7.42; 95% CI, 1.78-30.89) as independent risk factors for CNS relapse. In 80 advanced ENKTL patients, 18 received steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy as first-line treatment. Patients who received SMILE as their first-line treatment tended to have better OS than those who did not (p = 0.071). Six (7.5%) advanced ENKTL patients experienced isolated CNS relapse (median, 2.6 months after diagnosis) and died within 4 months of relapse. No second malignancies were documented in advanced ENKTL patients. In the entire cohort, the median OS after first relapse or progression was 4.6 months. 12 patients who survived 5 years after PFS events were disease-free at the last follow-up. Of those, 11 (92%) underwent hematopoietic stem cell transplantation. Our 8-year follow-up revealed the long-term efficacy and safety of RT-DeVIC and SMILE. The risk of CNS relapse is an important consideration in advanced ENKTL.

Mirabegron Reduces Urinary Frequency and Improves Overactive Bladder Symptoms at 3 Months After 125I-brachytherapy for Prostate Cancer: An Open-Labeled, Randomized, Non-Placebo-Controlled Study.

OBJECTIVE: To evaluate the additional effects of mirabegron to alpha-1 adrenergic antagonist on lower urinary tract symptoms of patients who underwent 125I-brachytherapy for prostate cancer. PATIENTS AND METHODS: Patients who underwent 125I-brachytherapy for prostate cancer (cT1-cT3aN0M0) in a single institute between September 2016 and October 2018 were enrolled in the randomized, non-placebo, open-labeled, paralleled study. Patients were randomly distributed (1:1) to combination group (tamsulosin (0.2 mg/day) plus mirabegron (50 mg/day)) or tamsulosin-alone group after 125I -brachytherapy by envelope method. The primary endpoint was the change from baseline in mean voided volume per micturition 3 months after 125I brachytherapy. The secondary endpoints included the changes from baseline of International Prostate Symptom Score, Overactive Bladder Symptom Score, and Expanded Prostate Cancer Index Composite scores and 24 hours urinary frequency after 3 months after 125I brachytherapy. RESULTS: The mean changes in volume voided per micturition in the combination (n = 108) and tamsulosin-alone (n = 110) groups were -62.5 (standard deviation, ±53.8) and -68.0 (standard deviation, ±52.7), respectively (P = .17). The change in Overactive Bladder Symptom Score in combination group (P = .02) was more moderate than in tamsulosin-alone group; and 24 hour urinary frequency in combination group was lower (P = .03) than in tamsulosin-alone group. Retention rates within 3 months after 125I-brachytherapy in the mirabegron and tamsulosin-alone groups were 7.3% (9/122) and 6.0% (7/118), respectively (P = .80). CONCLUSION: Tamsulosin and mirabegron combination therapy after 125I-brachytherapy did not improve voided volume per micturition compared to tamsulosin-only treatment. However, it could improve frequent urination and overactive bladder symptoms.

Erectile dysfunction and sexual quality of life in patients who underwent low-dose-rate brachytherapy alone for prostate cancer.

This study evaluated erectile function and sexual quality of life (QoL), and predictive factors for erectile dysfunction (ED) and the deterioration of sexual QoL in 70 patients who underwent low-dose-rate brachytherapy (LDR-BT) alone for prostate cancer without androgen deprivation therapy. Erectile function and sexual QoL were evaluated before and 1, 3, 6, 12, 24, 36, 48 and 60 months after LDR-BT. Binary logistic regression analysis was used to determine whether age, prostate volume, hypertension, diabetes, Brinkman's index, testosterone, baseline Sexual Health Inventory for Men (SHIM) score and post-implant dosimetry parameters could predict ED and deterioration of sexual QoL at 24 and 60 months after LDR-BT. After 24 and 60 months, ED was noted in 39 of 70 patients and 42 of 64 patients respectively. Furthermore, sexual QoL worsened in 42 of 70 and 43 of 64 patients respectively. Baseline SHIM score was identified as a significant predictor of ED (24 months: odds ratio [OR]: 0.83, p = 0.02; 60 months: OR: 0.83, p = 0.03) and the deterioration of sexual QoL (24 months: OR: 0.84, p = 0.03). LDR-BT for prostate cancer promoted decreased erectile function and sexual QoL, with high preimplant potency being a significant predictor of ED and the deterioration of sexual QoL.

Factors affecting urinary frequency after low-dose-rate brachytherapy for prostate cancer.

OBJECTIVES: Lower urinary tract symptoms are transiently exacerbated by low-dose-rate brachytherapy (LDR-BT) for prostate cancer and recover to pretreatment levels 1 year thereafter. Generally, these symptoms are influenced by temperature. We aimed to search for factors affecting the lower urinary tract symptoms after seed implant including seasons. METHODS: We retrospectively enrolled 812 patients who underwent LDR-BT at Nara Medical University Hospital from January 2010 to December 2018 and for whom the International Prostate Symptom Score, Overactive Bladder Symptom Score, and frequency volume charts were available. We investigated the relationships between lower urinary tract symptoms, 24-hours urinary frequency, 24-hours urinary volume before and after seed implant, radiation dose, and season of seed implant. RESULTS: The mean age was 69.5 years. The mean prostate volume was 24.2 mL. The International Prostate Symptom Score, Overactive Bladder Symptom Score, and 24-hours urinary frequency increased until 3 months and gradually decreased over 6 months after seed implant. Multiple linear regression analysis revealed that 24-hours urinary frequency at 3 months after seed implant was significantly influenced by external beam radiotherapy, larger prostate volume before implant, higher 24-hours urinary frequency at baseline, larger 24-hours urinary volume at 3 months after implant, and performance of implant in summer. CONCLUSIONS: Lower urinary tract symptoms worsened 3 months after seed implant of LDR-BT regardless of the season of implant. The urinary frequency 3 months after seed implant was slightly lower when seed implant was performed in the summer.

Impact of neoadjuvant androgen deprivation therapy on postimplant prostate D90 and prostate volume after low-dose-rate brachytherapy for localized prostate cancer.

OBJECTIVE: Higher quality of postimplant dosimetric evaluation is associated with higher biochemical recurrence-free survival rates after low-dose-rate brachytherapy for localized prostate cancer. Postimplant prostate D90 is a key dosimetric parameter showing the quality of low-dose-rate brachytherapy. In this study, to improve the quality of low-dose-rate brachytherapy for localized prostate cancer, we investigated pre-implant factors affecting the reduction of postimplant prostate D90. METHODS: A total of 441 patients underwent low-dose-rate brachytherapy monotherapy and 474 patients underwent low-dose-rate brachytherapy with external beam radiation therapy. Logistic regression analysis was carried out to identify predictive factors for postimplant D90 decline. The cut-off value of the D90 decline was set at 170 Gy and 130 Gy in the low-dose-rate brachytherapy monotherapy group and low-dose-rate brachytherapy with external beam radiation therapy group, respectively. RESULTS: On multivariate analysis, neoadjuvant androgen deprivation therapy was identified as an independent predictive factor for the decline of postimplant D90 in both the low-dose-rate brachytherapy monotherapy group (P < 0.001) and low-dose-rate brachytherapy with external beam radiation therapy group (P = 0.003). Prostate volume changes and computed tomography/transrectal ultrasound prostate volume ratio were significantly and negatively correlated with the postimplant D90. The prostate volume changes and computed tomography/transrectal ultrasound prostate volume ratio were significantly higher in patients with neoadjuvant androgen deprivation therapy than those without neoadjuvant androgen deprivation therapy (P < 0.001). CONCLUSIONS: Neoadjuvant androgen deprivation therapy decreased postimplant D90 with substantial prostate gland swelling after low-dose-rate brachytherapy. When neoadjuvant androgen deprivation therapy is required to reduce prostate volume for patients with large prostate glands and offer adequate local control for patients with high-risk prostate cancer before low-dose-rate brachytherapy, intraoperative D90 adjustment might be necessary.

Linac-based stereotactic radiosurgery and fractionated stereotactic radiotherapy with a micro-multileaf collimator for brain metastasis in the primary motor cortex.

This study aimed to assess the clinical outcomes of linear accelerators (linac)-based, stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) with a micro-multileaf collimator for brain metastasis in the primary motor cortex (BMPMC). Thirty-five consecutive patients with BMPMC who were treated by linac-based SRS or fSRT between January 2012 and March 2020 were analyzed. BMPMC was defined as a tumor located in the precentral gyrus on gadolinium-enhanced magnetic resonance imaging (MRI) and T2-weghted imaging (T2WI). In total, 35 patients with 37 metastases were analyzed. The median follow-up time was 13 (range: 1-97) months. The tumor volume was 0.05-26.5 (median: 0.62) cm3. All patients were treated with SRS or fSRT using 35 Gy with 7 Gy per fraction daily. The median survival time (MST) was 16.9 months. The pretreatment KPS and RPA class significantly differed in terms of MST on the log-rank tests. Seven symptomatic patients had hemiparesis before SRS or fSRT. All symptomatic patients, except one with facial paresis and one who died within 3 months, experienced improvement at a 3 month follow-up. None of the patients presented with persistent radiation injury at the final follow-up. Two patients presented with grade 3 radiation-related central nervous system necrosis, which was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. In BMPMC, SRS and fSRT had good tumor control and did not cause serious complications. Therefore, they are suitable treatment options with an acceptable safety profile.

Salvage Surgical Resection after Linac-Based Stereotactic Radiosurgery for Newly Diagnosed Brain Metastasis.

BACKGROUND: This study aimed to assess the clinical outcomes of salvage surgical resection (SSR) after stereotactic radiosurgery and fractionated stereotactic radiotherapy (SRS/fSRT) for newly diagnosed brain metastasis. METHODS: Between November 2009 and May 2020, 318 consecutive patients with 1114 brain metastases were treated with SRS/fSRT for newly diagnosed brain metastasis at our hospital. During this study period, 21 of 318 patients (6.6%) and 21 of 1114 brain metastases (1.9%) went on to receive SSR after SRS/fSRT. Three patients underwent multiple surgical resections. Twenty-one consecutive patients underwent twenty-four SSRs. RESULTS: The median time from initial SRS/fSRT to SSR was 14 months (range: 2-96 months). The median follow-up after SSR was 17 months (range: 2-78 months). The range of tumor volume at initial SRS/fSRT was 0.12-21.46 cm3 (median: 1.02 cm3). Histopathological diagnosis after SSR was recurrence in 15 cases, and radiation necrosis (RN) or cyst formation in 6 cases. The time from SRS/fSRT to SSR was shorter in the recurrence than in the RNs and cyst formation, but these differences did not reach statistical significance (p = 0.067). The median survival time from SSR and from initial SRS/fSRT was 17 and 74 months, respectively. The cases with recurrence had a shorter survival time from initial SRS/fSRT than those without recurrence (p = 0.061). CONCLUSIONS: The patients treated with SRS/fSRT for brain metastasis need long-term follow-up. SSR is a safe and effective treatment for the recurrence, RN, and cyst formation after SRS/fSRT for brain metastasis.

Comparison of disease-specific quality of life in prostate cancer patients treated with low-dose-rate brachytherapy: A randomized controlled trial of silodosin versus naftopidil.

OBJECTIVES: To compare the effects of naftopidil and silodosin administration on the quality of life of patients with prostate cancer who underwent low-dose-rate brachytherapy. METHODS: In total, 141 men diagnosed with localized prostate cancer who were treated with low-dose-rate brachytherapy were enrolled. Patients were randomized (1:1) to the naftopidil (75 mg/day, n = 63) or silodosin group (8 mg/day, n = 64). Naftopidil and silodosin were administered 1 day after low-dose-rate brachytherapy, and were continued for at least 3 months. Using the University of California at Los Angeles Prostate Cancer Index and Sexual Health Inventory for Men scores, the mean changes and rates of deterioration from baseline were compared. The deterioration rates in the quality of life of patients at 1 and 3 months after low-dose-rate brachytherapy were evaluated based on the minimal important difference. RESULTS: The rates of deterioration from baseline to 1 and 3 months after low-dose-rate brachytherapy were not significantly different between the two groups in terms of urinary function, urinary bother, bowel bother, sexual function or Sexual Health Inventory for Men scores. In contrast, there were significant differences in bowel function (naftopidil 1 month, 52%; 3 months, 52%; silodosin 1 month, 28%; 3 months, 34%; 1 month, P < 0.01; 3 months, P = 0.048) and sexual bother (naftopidil 3 months, 11%; silodosin 3 months, 29%; P = 0.01). CONCLUSIONS: Naftopidil and silodosin provide different disease-specific quality of life outcomes in patients undergoing, especially in terms of bowel function and sexual bother. These findings can help in the selection of α-1 adrenoceptor antagonists after low-dose-rate brachytherapy.

27-Hydroxycholesterol regulates human SLC22A12 gene expression through estrogen receptor action.

The excretion and reabsorption of uric acid both to and from urine are tightly regulated by uric acid transporters. Metabolic syndrome conditions, such as obesity, hypercholesterolemia, and insulin resistance, are believed to regulate the expression of uric acid transporters and decrease the excretion of uric acid. However, the mechanisms driving cholesterol impacts on uric acid transporters have been unknown. Here, we show that cholesterol metabolite 27-hydroxycholesterol (27HC) upregulates the uric acid reabsorption transporter URAT1 encoded by SLC22A12 via estrogen receptors (ER). Transcriptional motif analysis showed that the SLC22A12 gene promoter has more estrogen response elements (EREs) than other uric acid reabsorption transporters such as SLC22A11 and SLC22A13, and 27HC-activated SLC22A12 gene promoter via ER through EREs. Furthermore, 27HC increased SLC22A12 gene expression in human kidney organoids. Our results suggest that in hypercholesterolemic conditions, elevated levels of 27HC derived from cholesterol induce URAT1/SLC22A12 expression to increase uric acid reabsorption, and thereby, could increase serum uric acid levels.

Clinical questions on rehabilitation in cancer patients with skeletal metastasis: a content analysis of the multidisciplinary tumor board records.

PURPOSE: Cancer rehabilitation addresses the functional needs of patients who have various impairments. Disease control is a critical oncological consideration, while physical intervention increased weights of importance in several situations. To identify the clinical status that necessitates active physical intervention in cancer patients with skeletal metastasis, we performed a content analysis in the multidisciplinary tumor board (MDTB) records. METHODS: From January 2017 to September 2019, the MDTB discussed 168 consecutive patients with skeletal metastasis. We reviewed the MDTB records and asked responsible physicians to frame clinical questions. Based on these data, we identified the predictor valuables with the association to rehabilitation-related clinical questions using univariate and multivariate analyses. Moreover, we investigated a predictor of the change in Barthel index (BI) scores using univariate analyses. RESULTS: Rehabilitation-related questions arose more frequently in older patients (p = 0.011), in patients with slow-growth vs. rapid-growth tumor (p = 0.002), and in patients with skeletal-related events (p = 0.001) at MDTB. The tumor growth speed was associated with the change in BI scores, as slower-growth tumors had the benefit of BI gains (p = 0.017). CONCLUSIONS: Regarding rehabilitation in patients with skeletal metastasis, we should pay attention to three parameters: occurrence of skeletal events, patient age, and growth speed of tumors. Rehabilitation-related questions may reflect patients' functional needs that occur more frequently in patients with pathological fractures or neurological symptoms, older patients, and patients with slow-growth tumors.