Outcomes in patients with high- and very high-risk localized prostate cancer treated with definitive IMRT and long-term hormone therapy.

BACKGROUND: The aim of this study was to evaluate the effectiveness of intensity-modulated radiation therapy in combination with long-term androgen deprivation therapy for high-risk and very high-risk localized prostate cancer while also investigating factors associated with the therapeutic effect. METHODS: Men who fulfilled criteria for the National Comprehensive Cancer Network high-risk or very high-risk localized prostate cancer and were treated with definitive intensity-modulated radiation therapy (74-78 Gy) of the prostate and the seminal vesicle combined with androgen deprivation therapy in our institution from 2007 to 2016 were identified (n = 197). In principle, patients received androgen deprivation therapy for 3-6 months before radiation, concurrently, and for 2 years after completion of intensity-modulated radiation therapy. RESULTS: The median follow-up period was 96 months. The 5-year and 10-year overall survival rates in the overall population were 96.9% and 89.3%, respectively. The 5-year and 10-year cumulative incidence rates of biochemical failure were 2.5% and 16.3% in the high-risk group, and 8.6% and 32.0% in the very high-risk group, respectively, indicating a significant difference between the two groups (P = 0.023). Grade Group 5 and younger age (cutoff: 70 years old) were independent predictors of recurrence (P = 0.016 and 0.017, respectively). Patients exhibiting biochemical failure within <18 months after completion of androgen deprivation therapy displayed an increased risk of cancer-specific mortality (P = 0.039) when contrasted with those who had a longer interval to biochemical failure. CONCLUSIONS: Patients with the National Comprehensive Cancer Network very high-risk prostate cancer, particularly those with Grade Group 5 and younger age, showed worse outcomes following intensity-modulated radiation therapy and long-term androgen deprivation therapy.

Mental rotation ability and spontaneous brain activity: a magnetoencephalography study.

We performed experiments using magnetoencephalography to clarify the relationship between three-dimensional visuospatial abilities and spontaneous visual thinking characteristics. Subjects were divided into two groups based on the rate of correct answers to mental rotation tasks: those with good performances (Group G) and those with bad performances (Group B). We found the followings: (1) in the mental rotation tasks, the 25-35 Hz lower γ band activities in the superior parietal lobule/intraparietal sulcus regions and in the occipitotemporal region were significantly larger in Group G than in Group B and (2) in the spontaneous mental imagery tasks, the 20-Hz band activity in the left premotor cortex and the 35-Hz band activity in the supplementary motor area were significantly larger in Group G.

Aortic Dissection and Cardiac Dysfunction Emerged Coincidentally During the Long-Term Treatment with Angiogenesis Inhibitors for Metastatic Renal Cell Carcinoma.

Angiogenesis inhibitors, such as sorafenib and axitinib, which target vascular endothelial growth factor (VEGF) signaling, are widely used for renal cell carcinoma, including metastasis. In this study, we report a case of cardiovascular adverse events of aortic dissection and cardiac dysfunction during treatment with sorafenib and axitinib for metastatic renal cell carcinoma. A 66-year-old man had been administered sorafenib for 2 years after nephrectomy due to renal cell carcinoma. To control the progression of metastatic lung tumor, axitinib was started after sorafenib for four years. During the treatment, angiotensin II type 1 receptor blockers and Ca antagonists were used to strictly control the axitinib-induced hypertension and proteinuria. Aortic dissection and cardiac dysfunction occurred coincidentally. Considering the critical role of VEGF signaling in the homeostasis of the cardiovascular system, we speculated that the long-term use of axitinib and sorafenib directly influenced the initiation of aortic dissection and cardiac dysfunction. Although the precise mechanisms underlying the aortic dissection and cardiac dysfunction induced by angiogenesis inhibition are still elusive, onco-cardiologists and oncologists should pay careful attention to cardiovascular toxicity and complications in patients with cancer, particularly patients undergoing long-term cancer treatment.

Dynamic interactions of the cortical networks during thought suppression.

OBJECTIVES: Thought suppression has spurred extensive research in clinical and preclinical fields, particularly with regard to the paradoxical aspects of this behavior. However, the involvement of the brain's inhibitory system in the dynamics underlying the continuous effort to suppress thoughts has yet to be clarified. This study aims to provide a unified perspective for the volitional suppression of internal events incorporating the current understanding of the brain's inhibitory system. MATERIALS AND METHODS: Twenty healthy volunteers underwent functional magnetic resonance imaging while they performed thought suppression blocks alternating with visual imagery blocks. The whole dataset was decomposed by group-independent component analysis into 30 components. After discarding noise components, the 20 valid components were subjected to further analysis of their temporal properties including task-relatedness and between-component residual correlation. RESULTS: Combining a long task period and a data-driven approach, we observed a right-side-dominant, lateral frontoparietal network to be strongly suppression related. This network exhibited increased fluctuation during suppression, which is compatible with the well-known difficulty of suppression maintenance. CONCLUSIONS: Between-network correlation provided further insight into the coordinated engagement of the executive control and dorsal attention networks, as well as the reciprocal activation of imagery-related components, thus revealing neural substrates associated with the rivalry between intrusive thoughts and the suppression process.

Brain activities of visual thinkers and verbal thinkers: A MEG study.

In this study we measured activation patterns in the primary visual cortex and the frontal language areas and compared them in individuals with strong and weak capacities to mentally visualize information during spontaneous thinking. Subjects were first administered a 5-item questionnaire to assess their ability to create mental pictures, and were divided into two groups (strong and weak visualizers) on this basis. They then performed tasks requiring visual imagery and verbal recollection, and their local neural activities were measured, using magnetoencephalography (MEG). Notably in the high beta-band (25Hz), the visual area (BA 17) was more strongly activated in strong visualizers, whereas, the frontal language areas were more strongly activated in weak visualizers. Strong visualizers are considered to be visual thinkers, and weak visualizers are verbal thinkers.

Impact of hyponatremia on survival of patients with metastatic renal cell carcinoma treated with molecular targeted therapy.

OBJECTIVES: Hyponatremia is reported to be associated with poor survival in localized renal cell carcinoma and metastatic renal cell carcinoma treated with immunotherapy. However, there are no reports on the relationship between hyponatremia and prognosis of metastatic renal cell carcinoma treated with molecular targeted therapy. We evaluated the prognostic significance of hyponatremia in metastatic renal cell carcinoma treated with molecular targeted therapy as first-line therapy. METHODS: We retrospectively analyzed a database comprising 87 patients treated from April 2008 to July 2011 with sorafenib or sunitinib as first-line therapy for metastatic renal cell carcinoma. Patients were divided into three groups according to serum sodium level: severe hyponatremia (≤134 mEq/L), mild hyponatremia (135-137 mEq/L) and normal natremia (≥138 mEq/L). RESULTS: Median cancer-specific survival time was 8.8 months in the patients with severe and mild hyponatremia, and 32.6 months in the patients with normal natremia (P < 0.001). Multivariate analysis showed severe and mild hyponatremia to be significantly associated with cancer-specific survival (hazard ratio 6.228; 95% confidence interval 2.161-17.947, P = 0.001; hazard ratio 3.374; 95% confidence interval 1.294-8.798, P = 0.013), respectively. Neutrophilia and high C-reactive protein level (C-reactive protein ≥1.0 mg/dL) were significant prognostic factors to predict inferior cancer-specific survival. In Harrell's concordance index calculation, hyponatremia could significantly improve the predictive accuracy for estimation of survival probability (P = 0.028). CONCLUSIONS: Hyponatremia (<138 mEq/L), neutrophilia and high C-reactive protein levels seem to represent significant predictive factors for cancer-specific survival in metastatic renal cell carcinoma patients treated with molecular targeted therapy as first line therapy. Furthermore, hyponatremia might be significantly associated with chronic inflammation and tumor aggressiveness.

Clinical outcome and prognostic factors of sorafenib in Japanese patients with advanced renal cell carcinoma in general clinical practice.

OBJECTIVE: Effects of sorafenib in general clinical practice, especially those with patients of Asian ethnicity, have been rarely investigated. We assessed efficacy, safety and prognostic factors for progression-free survival in Japanese patients receiving sorafenib for advanced renal cell carcinoma. METHODS: We performed a retrospective analysis of 159 Japanese patients with renal cell carcinoma. Progression-free survival was estimated by the Kaplan-Meier method. Objective response (per Response Evaluation Criteria in Solid Tumors) and safety were assessed. Cox proportional hazards model was used to identify independent prognostic factors for progression-free survival. RESULTS: The median progression-free survival was 9.0 months (95% confidence interval, 7.5-10.6 months). In 142 patients with measurable lesions, the objective response rate was 21.8%, and disease control was achieved in 85 (59.9%) patients. Adverse events of any grade occurred in 152 patients (95.6%). Most common adverse events causing discontinuation or interruption of sorafenib were hand-foot skin reaction (22%), rash (10.7%) and liver dysfunction (10.7%). Dose reduction or therapy interruption due to adverse events was required in 128 patients (80.5%). Univariate and multivariate analysis revealed that favorable prognosis according to Memorial Sloan-Kettering Cancer Center prognostic factors and relative dose intensity during the first month of treatment of ≥50% were significant factors for predicting superior progression-free survival with sorafenib treatment. CONCLUSIONS: Sorafenib was effective in Japanese patients with advanced renal cell carcinoma in general clinical practice and was tolerated although most patients required dose reduction or interruption of therapy. Future studies should establish new strategies for treatment without sacrificing both efficacy and patient quality of life.

One-month relative dose intensity of not less than 50% predicts favourable progression-free survival in sorafenib therapy for advanced renal cell carcinoma in Japanese patients.

BACKGROUND: Sorafenib is a multikinase inhibitor used as a second-line treatment for metastatic renal cell carcinoma (mRCC). However, it is very difficult to estimate sorafenib dosage because it is difficult to maintain stable administration and dosage intervals due to several side-effects. We examined the correlation between relative dose intensity (RDI) and clinical outcome of sorafenib therapy in a multi-institutional study. METHODS: A study population of 70 first-line therapy-refractory patients with pathologically confirmed RCC was eligible for this investigation. Clinical outcomes were evaluated according to clinicopathological features and RDI for 1 month (1M-RDI). RESULTS: There was significant difference in progression-free survival (PFS) time but not overall survival (OS) time when the 1M-RDI cut-off value was ≥ 50%. In 15 patients (21.4%) with 1M-RDI of <50%, median PFS time was 4.1 months (95% I collagen (95% CI): 2.0-6.2), whereas it was 10.5 months (95% CI: 7.6-13.4) in the patients with 1M-RDI of ⩾50% (P=0.022). Multivariate analysis showed 1M-RDI status to be significantly associated with PFS (HR: 3.838, 95% CI: 1.658-8.883, P=0.002) but not OS (P=0.328). CONCLUSION: Although this study was retrospective, a 1M-RDI cut-off value of ≥ 50% for sorafenib may be the first factor to predict PFS but not OS in cytokine pretreated mRCC patients. The data indicate that a dose of 400mg/day of sorafenib administered successively for the first one month was necessary to prolong disease stabilisation and could be tolerated by Japanese patients.

Significance of electrostimulation in detecting neurovascular bundle during radical prostatectomy.

OBJECTIVE: The reported rate of erectile dysfunction after nerve-sparing prostatectomy varies according to physicians. Because exact preservation of the neurovascular bundle (NVB) solely depends on the judgment of the physician, he or she should try to correctly identify the NVB and also avoid neurophysiologic injury of the NVB during the procedure. The purpose of the present study is to assess the status of the NVB preservation by physician's judgment at the operation, the changes in intracavernous pressure related to intraoperative electrical stimulation and postoperative histopathological examination. PATIENTS AND METHODS: Thirty-eight patients who underwent nerve-sparing radical prostatectomy judged by intraoperative electrical stimulation of the NVB were included in this study. Bilateral, unilateral and non-nerve-sparing procedures were performed in 18, 17, and 3 cases, respectively. The NVB preservation evaluated by intraoperative physician's judgment was compared to that evaluated by postoperative histopathological examination. Furthermore, the NVB preservation evaluated by intraoperative electrical stimulation was compared to that by physician's judgment and postoperative histopathological examination. RESULTS: For 68 of 76 NVB (89.5%), intraoperative subjective judgment and histopathological assessment were identical. For 66 of 76 NVB (86.8%), electrical stimulation findings and the physician's judgments were identical, and for 70 of 76 NVB (92.1%), electrical stimulation findings and histopathological findings were identical. CONCLUSION: Even if physicians are convinced of a successful nerve-sparing procedure, there are some cases in which the NVB is not preserved accurately or neurophysiological damage is suffered. Therefore, intraoperative electrical stimulation of the NVB as well as the cavernosal nerve is very useful in evaluation of NVB preservation.