Six-year outcomes of robot-assisted radical prostatectomy versus volumetric modulated arc therapy for localized prostate cancer: A propensity score-matched analysis.

BACKGROUND: Although robot-assisted radical prostatectomy (RARP) and intensity-modulated radiotherapy are the leading respective techniques of prostatectomy and radiotherapy for localized prostate cancer, almost no study has directly compared their outcomes; none have compared mortality outcomes. METHODS: We compared 6­year outcomes of RARP (n = 500) and volumetric modulated arc therapy (VMAT, a rotational intensity-modulated radiotherapy, n = 360) in patients with cT1-4N0M0 prostate cancer. We assessed oncological outcomes, namely overall survival (OS), cancer-specific survival (CSS), radiological recurrence-free survival (rRFS), and biochemical recurrence-free survival (bRFS), using propensity score matching (PSM). We also assessed treatment-related complication outcomes of prostatectomy and radiotherapy. RESULTS: The median follow-up duration was 79 months (> 6 years). PSM generated a matched cohort of 260 patients (130 per treatment group). In the matched cohort, RARP and VMAT showed equivalent results for OS, CSS, and rRFS: both achieved excellent 6­year outcomes for OS (> 96%), CSS (> 98%), and rRFS (> 91%). VMAT had significantly longer bRFS than RARP, albeit based on different definitions of biochemical recurrence. Regarding complication outcomes, patients who underwent RARP had minimal (2.6%) severe perioperative complications and achieved excellent continence recovery (91.6 and 68.8% of the patients achieved ≤ 1 pad/day and pad-free, respectively). Patients who underwent VMAT had an acceptable rate (20.0%) of grade ≥ 2 genitourinary complications and a very low rate (4.4%) of grade ≥ 2 gastrointestinal complications. CONCLUSION: On the basis of PSM after a 6-year follow-up, RARP and VMAT showed equivalent and excellent oncological outcomes, as well as acceptable complication profiles.

Crackless high-aspect-ratio processing of a silica glass with a temporally shaped ultrafast laser.

In this Letter, we propose a crackless high-aspect-ratio processing method based on a temporally shaped ultrafast laser. The laser pulse is temporally split into two sub pulses: one with smaller energy is used to excite electrons but without ablation so that the applied pressure to the sample is weak, and the other one is used to heat the electrons and achieve material removal after it is temporally stretched by a chirped volume Bragg grating (CVBG). Compared with the conventional ultrafast laser processing, the crack generation is almost suppressed by using this proposed method. The hole depth increases more than 3.3 times, and the aspect ratio is improved at least 2.2 times. Moreover, processing dynamics and parameter dependence are further experimentally studied. It shows that the processing highly depends on the density of electrons excited by the first pulse (P1) and the energy of the second pulse (P2). This novel, to the best of our knowledge, method provides a new route for the precise processing of wide-bandgap materials.

Treatment with lysophosphatidic acid improves glomerulonephritis through the suppression of macrophage activation in a murine model of systemic lupus erythematosus.

OBJECTIVES: Several therapeutic agents have been developed and used for the clinical treatment of systemic lupus erythematosus (SLE). In cases where SLE is accompanied by severe organ failures, such as neuropsychiatric lupus erythematosus (NPSLE) and acute onset of lupus nephritis, the use of potent immunosuppressive drugs, such as cyclophosphamide, is necessary. However, potent immunosuppressive drugs are known to increase infection risks. Thus, the development of therapeutic agents with novel mechanisms is urgently required. Previously, we reported that treatment with lysophosphatidic acid (LPA) prevents depression-like behaviours by suppressing microglial activation in MRL/lpr mice. In this study, we examined whether the treatment with LPA improves glomerulonephritis by affecting systemic immunity in MRL/lpr mice. METHODS: Eighteen-week-old MRL/lpr mice were treated with a vehicle or LPA for 3 weeks. After treatment, the glomerular inflammation and damage parameters were compared between the 2 groups. Moreover, we examined the effects of LPA on immune cells by flow cytometry using isolated splenocytes. RESULTS: LPA treatment in MRL/lpr mice significantly reduced the daily urinary albumin content and suppressed the CD68-positive cells and Periodic acid-Schiff (PAS)-positive areas in the glomeruli. The treatment also suppressed plasma anti-dsDNA antibodies and inflammatory cytokines in MRL/lpr mice. Although LPA did not significantly affect the total number of splenocytes, the treatment significantly reduced CD11b+Ly6G-Ly6C- cells (mature macrophages), as well as CD11b+Ly6G-Ly6C-CD68+ cells (activated mature macrophages). CONCLUSIONS: These results suggest that LPA may improve glomerulonephritis by suppressing macrophage activation in MRL/lpr mice.

Comparative analysis of treatment decision-making in patients with localized prostate and cervical cancer: what influences receiving surgery or radiotherapy?

PURPOSE: This study focused on identifying the factors influencing the decision-making process in patients with localized prostate and cervical cancer in Japan and specifically examining the choice between surgery and radiotherapy. METHODS: Patients with specific cancer stages registered with a healthcare research company for whom radical surgery or radiotherapy was equally effective and recommended participated in this cross-sectional online survey. RESULTS: The responses of 206 and 231 patients with prostate and cervical cancer, respectively, revealed that both groups relied heavily on the physicians' recommendations (prostate: odds ratio (OR) = 40.3, p < 0.001; cervical: OR = 5.59, p < 0.001) and their impression of radiotherapy (prostate: OR = 9.22, p < 0.001; cervical: OR = 2.31, p < 0.001). Factors such as hypertension (OR = 6.48, p < 0.05), diabetes mellitus (OR = 9.68, p < 0.05), employment status (OR = 0.08, p < 0.01), and impressions of surgery (OR = 0.14, p < 0.01) also played a significant role in patients with prostate cancer. In contrast, the specialty of the physician (OR = 4.55, p < 0.05) proposing the treatment influenced the decision-making process of patients with cervical cancer. Information sources varied between the two groups: patients with prostate cancer were more inclined towards printed materials, whereas patients with cervical cancer were more inclined towards interpersonal relationships. CONCLUSION: Although several limitations, such as the sample and recall bias, were noted, this study emphasizes the role of psychosocial factors in the decision-making process and the requirement for tailored information sources.

Deregulated JNK signaling enhances apoptosis during hyperthermia.

PURPOSE: c-Jun N-terminal kinases (JNKs) comprise a subfamily of mitogen-activated protein kinases (MAPKs). The JNK group is known to be activated by a variety of stimuli. However, the molecular mechanism underlying heat-induced JNK activation is largely unknown. The aim of this study was to clarify how JNK activity is stimulated by heat. METHODS AND MATERIALS: The expression levels of various MAPK members in HeLa cells, with or without hyperthermia treatment, were evaluated via western blotting. The kinase activity of MAPK members was assessed through in vitro kinase assays. Cell death was assessed in the absence or presence of siRNAs targeting MAPK-related members. RESULTS: Hyperthermia decreased the levels of MAP3Ks, such as ASK1 and MLK3 which are JNK kinase kinase members, but not those of the downstream MAP2K/SEK1 and MAPK/JNK. Despite the reduced or transient phosphorylation of ASK1, MLK3, or SEK1, downstream JNK was phosphorylated in a temperature-dependent manner. In vitro kinase assays demonstrated that heat did not directly stimulate SEK1 or JNK. However, the expression levels of DUSP16, a JNK phosphatase, were decreased upon hyperthermia treatment. DUSP16 knockdown enhanced the heat-induced activation of ASK1-SEK1-JNK pathway and apoptosis. CONCLUSION: JNK was activated in a temperature-dependent manner despite reduced or transient phosphorylation of the upstream MAP3K and MAP2K. Hyperthermia-induced degradation of DUSP16 may induce activation of the ASK1-SEK1-JNK pathway and subsequent apoptosis.

Adherence to national guidelines for colorectal, breast, and cervical cancer screenings in Japanese workplaces: a survey-based classification of enterprises' practices into "overscreening," "underscreening," and "guideline-adherence screening".

BACKGROUND: Workplace cancer screening programs are determined as part of an employee's benefits package and health checkups are perceived positively. However, the current status of workplace cancer screening programs in Japan is unavailable. This study aimed to assess the adherence to national guidelines for colorectal, breast, and cervical cancer screenings in the workplace among Japanese enterprises and identify factors associated with excessive or inadequate screenings. METHODS: A cross-sectional study design was employed. Data were obtained from a survey conducted by the "Corporate Action to Promote Cancer Control" between November and December 2022 among registered partner enterprises in Japan. The survey included questions on background characteristics, cancer screening practices, and intervention approaches. The analysis included 432 enterprises that provided complete responses regarding colorectal, breast, and cervical cancer screenings. RESULTS: The guideline-adherence rates for colorectal, breast, and cervical cancer screenings in the workplace were 12.7%, 3.0%, and 8.8%, respectively. Enterprises had lower adherence to screening guidelines than local governments. Colorectal (70.8%) and breast (67.1%) cancer screenings were predominantly categorized as "overscreening" and cervical (60.6%) cancer screening, as "underscreening." Factors such as enterprise scale, health insurance associations, and the number of interventional approaches were significantly associated with increased "overscreening" (101-1000: ß = 0.13, p = 0.01; ≥ 1000: ß = 0.17, p < 0.01; health insurance association: ß = 0.23, p < 0.01; and approaches: ß = 0.42, p < 0.01) and reduced "underscreening" (101-1000: ß = -0.13, p = 0.01; ≥ 1000: ß = -0.17, p < 0.01; health insurance association: ß = -0.18, p < 0.01; and approaches: ß = -0.48, p < 0.01). CONCLUSION: Adherence to national guidelines for colorectal, breast, and cervical cancer screenings in the workplace was suboptimal among Japanese enterprises. Therefore, appropriate cancer screening measures and interventions to ensure guideline adherence and optimization of screening benefits while minimizing potential harms should be expeditiously implemented.

Relationship between hydrogel spacer distribution and dosimetric parameters in linear-accelerator-based stereotactic body radiotherapy for prostate cancer.

PURPOSE: To explore the potential of quantitative parameters of the hydrogel spacer distribution as predictors for separating the rectum from the planning target volume (PTV) in linear-accelerator-based stereotactic body radiotherapy (SBRT) for prostate cancer. METHODS: Fifty-five patients underwent insertion of a hydrogel spacer and were divided into groups 1 and 2 of the PTV separated from and overlapping with the rectum, respectively. Prescribed doses of 36.25-45 Gy in five fractions were delivered to the PTV. The spacer cover ratio (SCR) and hydrogel-implant quality score (HIQS) were calculated. RESULTS: Dosimetric and quantitative parameters of the hydrogel spacer distribution were compared between the two groups. For PTV, D99% in group 1 (n = 29) was significantly higher than that in group 2 (n = 26), and Dmax, D0.03cc, D1cc, and D10% for the rectum were significantly lower in group 1 than in group 2. The SCR for prostate (89.5 ± 12.2%) in group 1 was significantly higher (p < 0.05) than that in group 2 (74.7 ± 10.3%). In contrast, the HIQS values did not show a significant difference between the groups. An area under the curve of 0.822 (95% confidence interval, 0.708-0.936) for the SCR was obtained with a cutoff of 93.6%, sensitivity of 62.1%, and specificity of 100%. CONCLUSIONS: The SCR seems promising to predict the separation of the rectum from the PTV in linear-accelerator-based SBRT for prostate cancer.

Exploring the Correlation Between Health Literacy and Knowledge of Cervical Cancer and Radiotherapy Among Japanese Women: A Web-Based Survey.

Health literacy (HL) plays a vital role in an individual's ability to make informed health decisions. Japan faces several challenges in cervical cancer control, including low human papillomavirus (HPV) vaccination and screening rates, underutilization of radiotherapy, and limited HL. This study explored the association between HL and knowledge of cervical cancer and radiotherapy, particularly among young Japanese women. We conducted a web-based survey among users of LunaLuna, a popular women's healthcare application, to assess their HL and knowledge about cervical cancer and radiotherapy through a 46-question survey. We compared three groups in terms of HL (inadequate, problematic, and sufficient & excellent). Multiple regression analysis was used to identify factors associated with knowledge. In total, 1468 respondents were included in this study. HL was positively correlated with knowledge scores (inadequate: 51.8%; problematic: 56.3%; sufficient & excellent: 60%). Participants displayed relatively low accuracy for treatment-related questions. Higher HL (ß = 0.15, p < 0.01), education (ß = - 0.11, p < 0.01), cervical cancer screening (ß = - 0.11, p < 0.01), income (ß = 0.09, p < 0.01), and employment (ß = - 0.06, p = 0.04) were significant factors affecting knowledge of cervical cancer and radiotherapy. Our findings underscore the pivotal role of HL in promoting cervical cancer prevention and providing a better understanding of radiotherapy. Despite factors such as age, education, and history of cervical cancer screening, HL showed the strongest association with knowledge of cervical cancer and radiotherapy. The enhancement of HL and knowledge dissemination may be critical for promoting cervical cancer prevention and radiotherapy in Japan.

Treatment with lysophosphatidic acid prevents microglial activation and depression-like behaviours in a murine model of neuropsychiatric systemic lupus erythematosus.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is an incurable disease characterised by neuropsychiatric symptoms, particularly depression. Novel therapeutic options for NPSLE are urgently needed. Several previous reports have suggested that both microglial activation and impaired neurogenesis may be involved in the progression of depression. In contrast, the administration of lysophosphatidic acid (LPA) ameliorates depression and anxiety. Therefore, in the present study, we determined whether treatment with LPA affects microglial activation, impaired neurogenesis, and abnormal behaviour in MRL/lpr mice. In both tail suspension test and forced swim test, the MRL/lpr mice exhibited a significant increase in total immobility time compared with MRL/+ mice. Treatment with LPA significantly suppressed the prolonged immobility time in MRL/lpr mice. In contrast, pretreatment with ki16425 (a specific antagonist of LPA receptor 1 and 3) significantly reversed the effects of LPA. Furthermore, MRL/lpr mice exhibited impairments in spatial working memory and visual cognitive memory, which were suppressed by LPA treatment. The expression levels of TMEM119, CD68, GFAP, and caspase-3 in the hippocampus and prefrontal cortex of MRL/lpr mice were significantly higher than those in MRL/+ mice. Treatment with LPA inhibited these increases in MRL/lpr mice. Pretreatment with ki16425 reversed LPA-mediated inhibition of microglial activation. The quantity of sodium fluorescein that leaked into the brain tissues in MRL/lpr mice were significantly higher than that in MRL/+ mice. Treatment with LPA tended to decrease the sodium fluorescein leakage. These findings suggest that treatment with LPA may regulate microglial activation, which is important in the pathogenesis of NPSLE, as well as blood-brain-barrier weakening and abnormal behaviour.

Decrease in MAP3Ks expression enhances the cell death caused by hyperthermia.

PURPOSE: Hyperthermia is a promising anticancer treatment modality. However, the molecular mechanism underlying the thermal sensitivity of tumor cells is largely unknown. The aim of this study was to clarify how biochemical changes triggered by heat stimulate antitumor activity. METHODS AND MATERIALS: The expression levels of various MAPK members in HeLa cells with or without hyperthermia were evaluated by western blotting and RT-PCR. The intracellular Ca2+ concentration [Ca2+]i was monitored by digital imaging using CaTM-2 AM. An in vitro cleavage assay was used to determine whether calcium-dependent protease calpain cleaves MAPK components. Cell proliferation and clonogenicity were assessed in the absence or presence of siRNAs targeting MAPK members. RESULTS: Hyperthermia decreased the levels of MAP3K TAK1, RAF1 and MEKK2 but not of the downstream MAP2K and MAPK members. The hyperthermia-induced degradation of TAK1 and MEKK2 was rescued by either the proteasome inhibitor MG132 or the calpain inhibitor ALLN; however, RAF1 was not affected by the inhibitors. Heat induced down regulation of RAF1. Hyperthermia increased [Ca2+]i and calpain I expression. The calcium ionophore A23187 decreased TAK1 and MEKK2 levels. An in vitro cleavage assay demonstrated that TAK1 and MEKK2 are calpain I substrates. Knockdown of TAK1, RAF1 and MEKK2 suppressed cell proliferation and clonogenicity. CONCLUSIONS: Hyperthermia decreased the levels of MAP3K TAK1, RAF1 and MEKK2, without reduction of the downstream components in the MAP3K-MAP2K-MAPK cascade, by a calpain-dependent degradation pathway or transcriptional regulation. TAK1, RAF1 and/or MEKK2 play crucial roles in cell proliferation and clonogenicity and are potential molecular targets for hyperthermia.

Translocation of HSP47 and generation of mitochondrial reactive oxygen species in human neuroblastoma SK-N-SH cells following electron and X-ray irradiation.

Generation of mitochondrial reactive oxygen species (ROS), lipid peroxidation, 4-hydroxy-2-nonenal, and heat-shock protein (HSP) 47 after electron and X-ray irradiations were detected in the human neuroblastoma cell line SK-N-SH. After 10 Gy electron irradiation and 15 Gy X-ray irradiation, mitochondrial ROS production and lipid peroxidation were significantly increased. Additionally, we observed a significant increase in the levels of HSP47 after 3 and 10 Gy electron irradiation as well as 15 Gy X-ray irradiation. Furthermore, myristoylation and farnesylation were increased after 10 Gy electron and 15 Gy X-ray irradiations. We found that the level of HSP47 increased in the mitochondria after 10 Gy electron and 15 Gy X-ray irradiations. HSP47 coexisted with myristoylation and farnesylation. Furthermore, HSP47 overexpression increased mitochondrial ROS production. These results suggest that HSP47 plays an important role in mitochondria and induces mitochondrial ROS production in SK-N-SH cells.

Sequentially timed all-optical mapping photography boosted by a branched 4f system with a slicing mirror.

We present sequentially timed all-optical mapping photography (STAMP) with a slicing mirror in a branched 4f system for an increased number of frames without sacrificing pixel resolution. The branched 4f system spectrally separates the laser light path into multiple paths by the slicing mirror placed in the Fourier plane. Fabricated by an ultra-precision end milling process, the slicing mirror has 18 mirror facets of differing mirror angles. We used the boosted STAMP to observe dynamics of laser ablation with two image sensors which captured 18 subsequent frames at a frame rate of 126 billion frames per second, demonstrating this technique's potential for imaging unexplored ultrafast non-repetitive phenomena.

Efficacy of a hydrogel spacer in three-dimensional conformal radiation therapy for prostate cancer.

OBJECTIVES: We aimed to compare the dose constraints fulfillment rate of the three-dimensional conformal radiotherapy treatment plan before and after a hydrogel spacer insertion. METHODS: The planning computed tomography scans of 39 patients who received stereotactic body radiotherapy for prostate cancer were used. All patients inserted a hydrogel spacer and underwent computed tomography scans before and after spacer insertion. The three-dimensional conformal radiotherapy plans according to NCCN classification, low-, intermediate- and high-risk, were made for each patient. Clinical target volume included prostate and seminal vesicle 2 cm for high risk, prostate and seminal vesicle 1 cm for intermediate risk and prostate only for low risk. Three-dimensional conformal radiotherapy including a seven-field conformal technique with 76 Gy in 38 fractions. Dose constraints for rectum and bladder were V70 Gy ≤ 15%, V65 Gy ≤ 30% and V40 Gy ≤ 60%. RESULTS: Among 39 patients, 35 (90%), 19 (49%) and 13 (33%) and 38 (97%), 38 (97%) and 34 (87%) patients before and after the spacer insertion fulfilled rectum dose constraints for low-, intermediate- and high-risk plans, respectively. A hydrogel spacer significantly reduced rectum dose and improved the rectum dose constraints fulfillment rate in intermediate (P < 0.01) and high (P < 0.01), but no difference was found in low-risk plan (P = 0.25). On multivariate analysis, spacer use was associated with the higher rectum dose constraints fulfillment rate. CONCLUSIONS: A hydrogel spacer reduced rectum dose and improved the dose constraints fulfillment rate in three-dimensional conformal radiotherapy plan. Although IMRT is the standard treatment, 3D-CRT using a hydrogel spacer may be a treatment option.

Surface and build-up dose comparison between Elekta 6 MV flattening filter and flattening-filter-free beams using an advanced Markus ionization chamber and a solid water-equivalent phantom.

Using a plane-parallel advanced Markus ionization chamber and a stack of water-equivalent solid phantom blocks, percentage surface and build-up doses of Elekta 6 MV flattening filter (FF) and flattening-filter-free (FFF) beams were measured as a function of the phantom depth for field sizes ranging from 2 × 2 to 10 × 10 cm2 . It was found that the dose difference between the FF and the FFF beams was relatively small. The maximum dose difference between the FF and the FFF beams was 4.4% at a depth of 1 mm for a field size of 2 × 2 cm2 . The dose difference was gradually decreased while the field size was increased up to 10 × 10 cm2 . The measured data were also compared to published Varian FF and FFF data, suggesting that the percentage surface and build-up doses as well as the percentage dose difference between FF and FFF beams by our Elekta linac were smaller than those by the Varian linac.

[Improvement in Image Quality of CBCT during Treatment by Cycle Generative Adversarial Network].

PURPOSE: Volumetric modulated arc therapy (VMAT) can acquire projection images during rotational irradiation, and cone-beam computed tomography (CBCT) images during VMAT delivery can be reconstructed. The poor quality of CBCT images prevents accurate recognition of organ position during the treatment. The purpose of this study was to improve the image quality of CBCT during the treatment by cycle generative adversarial network (CycleGAN). METHOD: Twenty patients with clinically localized prostate cancer were treated with VMAT, and projection images for intra-treatment CBCT (iCBCT) were acquired. Synthesis of PCT (SynPCT) with improved image quality by CycleGAN requires only unpaired and unaligned iCBCT and planning CT (PCT) images for training. We performed visual and quantitative evaluation to compare iCBCT, SynPCT and PCT deformable image registration (DIR) to confirm the clinical usefulness. RESULT: We demonstrated suitable CycleGAN networks and hyperparameters for SynPCT. The image quality of SynPCT improved visually and quantitatively while preserving anatomical structures of the original iCBCT. The undesirable deformation of PCT was reduced when SynPCT was used as its reference instead of iCBCT. CONCLUSION: We have performed image synthesis with preservation of organ position by CycleGAN for iCBCT and confirmed the clinical usefulness.

Nonlinear photoacoustic waves for light guiding to deep tissue sites.

Light scattering by tissues limits performance in biological sensing or stimulation. Here we present a photoacoustic technique that increases light transmittance by one order of magnitude and enables light localization in deep tissue. Laser-induced nonlinear acoustic waves are utilized to produce a high refractive index contrast in scattering medium without high-intensity pressure. The size of guiding area is around 60 µm, which is equivalent or smaller than the diameter of multimode fibers. To show potential use in biomedical fields, we performed light guiding and imaging of fluorescence, through swine tissues with thickness more than 1 mm.

Undetected human papillomavirus DNA and uterine cervical carcinoma: Association with cancer recurrence.

BACKGROUND: The time course of human papillomavirus (HPV) DNA clearance was studied in patients with carcinoma of the cervix during follow-up after primary radical radiotherapy (RT). This study investigated the relationship between timing of HPV clearance and RT effectiveness. PATIENTS AND METHODS: A total of 71 consecutive patients who were treated for cervical cancer with primary radical radiotherapy and high-dose rate intracavitary brachytherapy with or without chemotherapy were enrolled in the study. Samples for HPV DNA examination were taken before (1) treatment, (2) every brachytherapy, and (3) every follow-up examination. The times when HPV DNA was undetected were analyzed for association with recurrence-free survival. RESULTS: HPV DNA was not detected in 13 patients (18 %) before RT. Of the 58 patients with HPV DNA detected before treatment, HPV DNA was not detected in 34 % during treatment and in 66 % after the treatment. Within 6 months after RT, HPV DNA was detected in 0 % of all patients. The patients were followed up for a median period of 43 months (range 7-70 months). In all, 20 patients were found to develop recurrence. The 3-year cumulative disease-free survival (DFS) rate was 71 ・} 5.4 % for all 71 patients. In multivariate analysis, DFS was significantly associated with HPV (detected vs. not detected) with a hazard ratio of 0.07 (95 % confidence interval 0.008-0.6, p = 0.009). CONCLUSION: In this study, patients in whom HPV was not detected had the worst prognosis. Six months after RT, HPV DNA was detected in 0 % of the patients. Patients in whom HPV DNA could not be detected before treatment need careful follow-up for recurrence and may be considered for additional, or alternative treatment.

Lung stereotactic radiotherapy for oligometastases: comparison of oligo-recurrence and sync-oligometastases.

BACKGROUND: Oligometastases can be divided into sync-oligometastases and oligo-recurrence. The difference is whether the primary site is uncontrolled or controlled. The goal of this multicenter study was to evaluate treatment outcomes and factors affecting survival after stereotactic body radiotherapy for pulmonary oligometastases. METHODS: The information after stereotactic body radiotherapy from January 2004 to April 2014 was retrospectively collected. Ninety-six patients (65 males, 31 females) were enrolled. Ten cases (10%) were sync-oligometastases, 79 cases (82%) were oligo-recurrences and 7 (7%) were unclassified oligometastases with <6 months of disease-free interval. The median disease-free interval between initial therapy and stereotactic body radiotherapy was 24 months. The median calculated biological effective dose was 105.6 Gy. RESULTS: The median follow-up period was 32 months for survivors. The 3-year overall survival and relapse-free survival rates were 53% and 32%, respectively. No Grade 5 toxicity occurred. The median overall survival was 23.9 months for sync-oligometastases and 66.6 months for oligo-recurrence (P = 0.0029). On multivariate analysis, sync-oligometastases and multiple oligometastatic tumors were significant unfavorable factors for both overall survival and relapse-free survival. CONCLUSIONS: In stereotactic body radiotherapy for oligometastatic lung tumors, the state of oligo-recurrence has the potential of a significant prognostic factor for survival.

Impact of Gleason pattern 5 including tertiary pattern 5 on outcomes of salvage treatment for biochemical recurrence in pT2-3N0M0 prostate cancer.

BACKGROUND: Gleason pattern 5 (GP5), including tertiary GP5, at radical prostatectomy has reportedly been associated with poorer clinical outcome. However, it is undetermined how tertiary GP5 is handled in the new Gleason grade grouping starting in 2016, and its prognostic value in patients undergoing salvage treatment for postoperative biochemical recurrence (BCR) remains unclear. METHODS: We retrospectively reviewed 116 patients with pT2-3N0M0 prostate cancer (PC) who received salvage treatment for BCR after radical prostatectomy between 2003 and 2014. The primary endpoint was failure of salvage treatment, defined as a single prostate-specific antigen (PSA) value ≥0.2 ng/ml after PSA nadir following salvage treatment. Associations of various clinicopathological factors, including GP5, with failure-free survival were assessed. Cox proportional hazards model was used for multivariate analysis. RESULTS: Patients received salvage treatment with either radiotherapy (n = 48), androgen-deprivation therapy (n = 61), or both (n = 7) for BCR. Twenty-three patients (19.8 %) experienced failure of salvage treatment, with a median follow-up period of 79 months. Univariate analysis associated GP5, Gleason score-based parameters, lymphovascular invasion, and PSA doubling time <6 months with poorer failure-free survival. Receiver operating characteristic curve analyses identified the area under the curve for GP5 (0.654) as the largest among those parameters (P = 0.0060). Multivariate analysis demonstrated that GP5 was the only independent predictor of poor outcome. CONCLUSIONS: The presence of GP5 is an independent predictor of poor prognosis in patients with pT2-3N0M0 PC undergoing salvage treatment for BCR after radical prostatectomy. GP5 may thus be a more useful marker than conventional Gleason score in this setting.

[Evaluation of a Post-analysis Method for Cumulative Dose Distribution in Stereotactic Body Radiotherapy].

PURPOSE: The purpose of this study was to evaluate a post-analysis method for cumulative dose distribution in stereotactic body radiotherapy (SBRT) using volumetric modulated arc therapy (VMAT) . METHOD: VMAT is capable of acquiring respiratory signals derived from projection images and machine parameters based on machine logs during VMAT delivery. Dose distributions were reconstructed from the respiratory signals and machine parameters in the condition where respiratory signals were without division, divided into 4 and 10 phases. The dose distribution of each respiratory phase was calculated on the planned four-dimensional CT (4DCT). Summation of the dose distributions was carried out using deformable image registration (DIR), and cumulative dose distributions were compared with those of the corresponding plans. RESULTS AND DISCUSSION: Without division, dose differences between cumulative distribution and plan were not significant. In the condition where respiratory signals were divided, dose differences were observed over dose in cranial region and under dose in caudal region of planning target volume (PTV). Differences between 4 and 10 phases were not significant. CONCLUSION: The present method was feasible for evaluating cumulative dose distribution in VMAT-SBRT using 4DCT and DIR.