Phase II trial of biweekly administration with eribulin after three cycles of induction therapy in hormone receptor-positive, HER2-negative metastatic breast cancer (JACCRO BC-03).

PURPOSE: Metastatic breast cancer (MBC) is usually incurable; treatment aims to maximize patients' function and quality of life (QOL). Eribulin is a standard treatment in patients with MBC pretreated with anthracycline and taxane; however, the best administration schedule is unknown. METHODS: In this prospective phase II trial of patients with luminal MBC, we administered biweekly eribulin to patients who completed a three-cycle induction treatment. RESULTS: Sixty patients with hormone-receptor-positive and HER2-negative MBC were enrolled; 40 obtained stable disease (SD) or better efficacy after induction therapy, after which they were switched to biweekly maintenance administration. The median progression-free survival (PFS) in patients who switched to maintenance therapy was 15.21 weeks (95% CI 9.71-22.14), starting on the first day of maintenance therapy. Overall survival (OS) in patients who switched to maintenance therapy was 21.39 months (95% CI 18.89-32.89). PFS and OS in the whole population starting from the registration date were 19.00 weeks (95% CI 17.00-25.00) and 21.52 months (95% CI 16.23-24.25), respectively. PFS from the enrollment date for patients who received maintenance therapy was 25.29 weeks (95% CI 19.14-32.14). Patients who achieved complete response or partial response during induction therapy had significantly longer PFS compared to patients with SD. CONCLUSION: The efficacy of biweekly administration of eribulin at maintenance was nonsignificant. However, less frequent visits are convenient, and reduced dose intensity improves safety. Biweekly administration, besides dose reduction, could be an acceptable option for patients who are unable to maintain a standard regimen.

Risk Profiling of Cancer Treatment-Related Cardiovascular Disorders in Breast Cancer Patients Who Received Adjuvant Chemotherapy With Trastuzumab.

Background: The prognosis of cancer survivors has dramatically improved, but effective strategies for cancer treatment-related cardiovascular disorders (CTRCD) remain to be elucidated in the emerging field of cardio-oncology. In this study, we investigated risk factors for CTRCD in breast cancer patients treated with trastuzumab. Methods and Results: We performed a retrospective analysis of 141 consecutive women who received adjuvant trastuzumab, and underwent baseline (BL) and follow-up (FU) echocardiography at Juntendo University between April 2010 and December 2016. The major concomitant treatment was anthracyclines in 94% and radiotherapy in 53%. During the median treatment period of 11 months, there were 22 (15.6%) cardiology consultations, 3 (2.1%) treatment interruptions with irreversible CTRCD, and no deaths. Left ventricular ejection fraction (LVEF) was decreased from a median 67.5% (BL) to 63.4% (FU; P<0.0001), with reduced LVEF noted in 26.2% at FU<90%BL, in 13.5% at FU

Overcoming the Adverse Effects of Everolimus to Achieve Maximum Efficacy in the Treatment of Inoperable Breast Cancer: A Review of 11 Cases at Our Hospital.

Everolimus is an effective treatment for advanced and/or metastatic breast cancer, especially in hormone receptor-positive cases. However, adverse events have prevented considerable numbers of clinicians from using this drug. Herein, we reviewed our clinical experiences and endeavored to identify patients in whom the benefits of everolimus treatment would outweigh these adverse events. If measures were available to prevent or minimize adverse effects prior to treatment, everolimus would be a more widely applicable drug. This retrospective study involved 11 patients in whom nonresectable or recurrent breast cancers were treated with everolimus between April 2014 and January 2016. Two patients achieved a partial response (PR) and 4 showed stable disease (SD) (1 showed long SD, i.e., > 24 weeks). The response rate was 18%, and the clinical benefit rate (PR + long SD) was 27%. Regarding adverse events, interstitial pneumonia (grade 3) developed in 3 patients (18%), necessitating treatment discontinuation. When using everolimus, it may be important to select suitable patients for whom this treatment can be continued with sufficient control of adverse events. Herein, we provide information relevant to the clinical use of everolimus based on our daily practice experiences with this agent.

Trypophobic Discomfort is Spatial-Frequency Dependent.

Clusters of holes, such as those in a lotus seedpod, induce trypophobic discomfort. Previous research has demonstrated that high-contrast energy at midrange spatial frequencies in images causes trypophobic discomfort. The present study examined the effects on discomfort of eliminating various spatial frequency components from the images to reveal how each spatial frequency contributes to the discomfort. Experiment 1 showed that eliminating midrange spatial frequencies did not affect trypophobic discomfort, while Experiment 2 revealed that images of holes that consisted of only high-spatial frequencies evoked less discomfort than other images and that images containing only low or midrange spatial frequencies induced as much trypophobic discomfort as did the original images. Finally, Experiment 3 found that participants with a high level of the trypophobic trait experienced stronger discomfort from the original images and the images containing only low or midrange spatial frequencies than participants with a low level of the trypophobic trait. Our findings thus suggest that trypophobic discomfort can be induced by middle and low spatial frequencies.

Cross-cultural validity of the theory of planned behavior for predicting healthy food choice in secondary school students of Inner Mongolia.

AIMS: Unhealthy eating behavior is a serious health concern among secondary school students in Inner Mongolia. To predict their healthy food choices and devise methods of correcting unhealthy choices, we sought to confirm the cross-cultural validity of the theory of planned behavior among Inner Mongolian students. MATERIALS AND METHODS: A cross-sectional study, conducted between November and December 2014. Overall, 3047 students were enrolled. We devised a questionnaire based on the theory of planned behavior to measure its components (intentions, attitudes, subjective norms, and perceived behavioral control) in relation to healthy food choices; we also assessed their current engagement in healthy food choices. RESULTS: A principal component analysis revealed high contribution rates for the components (69.32%-88.77%). A confirmatory factor analysis indicated that the components of the questionnaire had adequate model fit (goodness of fit index=0.997, adjusted goodness of fit index=0.984, comparative fit index=0.998, and root mean square error of approximation=0.049). Notably, data from participants within the suburbs did not support the theory of planned behavior construction. Several paths did not predict the hypothesis variables. However, attitudes toward healthy food choices strongly predicted behavioral intention (path coefficients 0.49-0.77, p<0.01), regardless of demographic characteristics. CONCLUSION: Our results support that the theory of planned behavior can apply to secondary school students in urban areas. Furthermore, attitudes towards healthy food choices were the best predictor of behavioral intentions to engage in such choices in Inner Mongolian students.

Effect of telling patients their "spirometric-lung-age" on smoking cessation in Japanese smokers.

BACKGROUND: Cigarette smoking remains a significant public health problem. However, current treatment programs have not yet succeeded in sufficiently reducing smoking rates. The study aimed to examine whether patients' recognition of "spirometric-lung-age (SLA)" estimated from spirometry data prompts smoking cessation. METHODS: From December 2010 to September 2011, participating smokers were prospectively enrolled into the standardized smoking cessation program (Visits 1-5 for 12 weeks) and assigned single-blindly to either SLA assessment or control groups. The SLA group was informed of the estimated age of their lungs from spirometry analysis and given an opportunity to recognize the difference from their actual chronological age, whereas the control group was not. The primary calculation of outcome was the smoking quit rate on Visit 5, whereas the secondary end-point was the proportion of patients who remained abstinent 1 year later. RESULTS: One hundred and twenty-six Japanese smokers (88 males) participated and were randomly assigned to the SLA group (n=52) or the control group (n=74). The smoking quit rate on Visit 5 was similar in the SLA assessment group and control group (59.6% vs. 41.9%; P=0.0700). However, the proportion of patients who remained abstinent 1 year later was similar in both groups (78.6% vs. 69.0%; P=0.5497). Multivariate logistic regression analysis after adjusting baseline characteristics demonstrated that telling patients their SLA, the use of varenicline, and age were significantly associated with smoking quit rate on Visit 5 whereas only age was associated with remaining abstinent 1 year later. CONCLUSIONS: Telling patients their SLA can become a useful tool prompting smoking cessation among Japanese smokers although other factors such as pharmacotherapy and age also influence the cessation of smoking.

Crossmodal Modulation of Spatial Localization by Mimetic Words.

The present study investigated whether aurally presented mimetic words affect the judgment of the final position of a moving object. In Experiment 1, horizontal apparent motion of a visual target was presented, and an auditory mimetic word of "byun" (representing rapid forward motion), "pitari" (representing stop of motion), or "nisahi" (nonsense syllable) was presented via headphones. Observers were asked to judge which of two test stimuli was horizontally aligned with the target. The results showed that forward displacement in the "pitari" condition was significantly smaller than in the "byun" and "nisahi" conditions. However, when non-mimetic but meaningful words were presented (Experiment 2), this effect did not occur. Our findings suggest that the mimetic words, especially that meaning stop of motion, affect spatial localization by means of mental imagery regarding "stop" established by the phonological information of the word.

[Immune Checkpoint for a Kidney Cancer and Other Cancers].

Immune checkpoint inhibitors have been getting increasing attention in the field of cancer treatment, resulting in the investigation of numerous drugs and target cancers. Clinical trials of immune checkpoint inhibitors have focused on malignant melanomas and non-small cell lung cancer;however, recently, clinical trials have been carried out for other cancers. To date, 31 phase III clinical trials have been conducted for 13 types of cancer. Recently, the results of the CheckMate025 kidney cancer and CheckMate141 head and neck cancer trials have been reported. These reports showed that nivolumab significantly enhanced overall survival in comparison to that associated with an existing second-line treatment drug. Based on these results, the approval of nivolumab for use in renal cell cancer and head and neck cancer is expected in the near future. Furthermore, the results of 20 phase III clinical trials will be submitted from 2017 to 2019, expanding the approval of immune checkpoint inhibitors. However, many issues such as biomarker searches, the evaluation of antitumor effects, and the impact on medical economy remain to be resolved. In this report, we outline clinical trial trends and the future prospects for immune checkpoint inhibitors.

Effect of motion coherence on time perception relates to perceived speed.

The present study examined the effect of coherence of moving visual objects on time perception. Participants observed stimuli composed of four line segments moving behind or in front of occluders. The line segments appeared to move either coherently as a diamond outline or incoherently, depending on the occlusion. Results from the temporal bisection task indicated that the duration of the coherently moving stimulus was perceived longer or shorter compared to the duration of the incoherently moving stimulus depending on the stimulus configurations. The speed comparison task revealed that the trend of the difference in perceived speed between the coherent and incoherent motions in each stimulus configuration was consistent with that of the difference in perceived duration between them. These results demonstrate the effect of motion coherence on perceived duration, and that this effect may be mediated by changes in perceived speed. Our finding provides evidence supporting the involvement of global motion processing in time perception.

Emotion biases voluntary vertical action only with visible cues.

Emotional information influences our bodily experiences according to the space-valence metaphor (positive/negative is up/down). In the present study, we examined whether visible and invisible emotional stimuli could also modulate voluntary action. After observing an emotional image (e.g., positive, neutral, or negative), participants used a joystick to arbitrarily position a dot stimulus in a display. The emotional image was either masked (masked condition) or not (unmasked condition) via a continuous flash suppression technique, i.e., dynamic interocular masking. We found that in the unmasked condition, the placed position of the dot was significantly higher after observing the positive image compared with the negative image, but this difference was not present in the masked condition. Our findings suggest that conscious emotional information is necessary for activating sensorimotor representations of vertical directions, and voluntary action is performed based on these activations.

A case report of using nivolumab for a malignant melanoma patient with rheumatoid arthritis.

The use of antibodies against programmed cell death 1 (PD-1), which block inhibitory T cell checkpoints, is a promising new therapy for advanced malignant melanoma and NSCLC. However, patients with autoimmune diseases were excluded at the clinical trial using such immune checkpoint inhibitor, because of the possibilities to worsen an adverse event of the autoimmune disease. Thus, the efficacy and toxicity of nivolumab using such cases have not been reported yet. A 70-year-old woman with bone and duodenal metastasis of primary mucosal melanoma with complications of the rheumatoid arthritis was treated with nivolumab. After 4 weeks injection of nivolumab, bone metastasis was diminished. After receiving six courses of nivolumab therapy, she maintained a complete response for 9 months, without rheumatic exacerbation or drug-related adverse events. Establishment of the biomarker of the effect prediction of the PD-1 antibody, the adverse event prediction will be important in future.

[Pharmacological Treatment for Bone Metastasis].

An objective of improvement of treatment outcomes of cancer is alleviation of bone metastasis that occurs in many types of cancers. Recently, the guidelines for the diagnosis and treatment of bone metastasis were published by the Japanese Society of Medical Oncology in cooperation with other groups. These guidelines are essentially evidence based for the pharmacological treatment of bone metastasis by using bone modifying agents (BMA). Cancer cells inhibit osteoblast formation and promote osteoclast proliferation. Many growth factors that are produced by the bone marrow promote osteoclast proliferation. Furthermore, many growth factors enhance the rate of cancer cell growth. These processes underlie bone metastasis. Evidence for the effectiveness of BMA for the treatment of lung cancer, breast cancer, prostate cancer, multiple myeloma, and other cancers is provided in each section of the guidelines. These guidelines also provide evidence for the suppression of skeletal related events (SRE) in lung, breast, and prostate cancers. With regard to multiple myeloma, the guidelines provide evidence for the improvement of overall survival in addition to that for suppression of SRE. Based on these evidences, the guidelines recommend aggressive treatment with BMA for bone metastasis in such cancers.

Post-determined emotion: motor action retrospectively modulates emotional valence of visual images.

Upward and downward motor actions influence subsequent and ongoing emotional processing in accordance with a space-valence metaphor: positive is up/negative is down. In this study, we examined whether upward and downward motor actions could also affect previous emotional processing. Participants were shown an emotional image on a touch screen. After the image disappeared, they were required to drag a centrally located dot towards a cued area, which was either in the upper or lower portion of the screen. They were then asked to rate the emotional valence of the image using a 7-point scale. We found that the emotional valence of the image was more positive when the cued area was located in the upper portion of the screen. However, this was the case only when the dragging action was required immediately after the image had disappeared. Our findings suggest that when somatic information that is metaphorically associated with an emotion is linked temporally with a visual event, retrospective emotional integration between the visual and somatic events occurs.

Time-to-contact estimation modulated by implied friction.

The present study demonstrated that friction cues for target motion affect time-to-contact (TTC) estimation. A circular target moved in a linear path with a constant velocity and was gradually occluded by a static rectangle. The target moved with forward and backward spins or without spin. Observers were asked to respond at the time when the moving target appeared to pass the occluder. The results showed that TTC was significantly longer in the backward spin condition than in the forward and without-spin conditions. Moreover, similar results were obtained when a sound was used to imply friction. Our findings indicate that the observer's experiential knowledge of motion coupled with friction intuitively modulated their TTC estimation.

Weight lifting can facilitate appreciative comprehension for museum exhibits.

Appreciation of exhibits in a museum can be equated to a virtual experience of lives in the contexts originally surrounding the exhibits. Here we focus on the importance of weight information, and hence tested whether experiencing a weight during museum exhibit appreciation affects the beholders' satisfaction and recognition memory for the exhibits. An experiment was performed at a museum exhibiting skeletal preparations of animals. We used nine preparations and prepared four weight stimuli as weight cues in accordance with the actual weight of four of the preparations: Remaining five preparations was displayed without weight stimuli. In the cued condition, participants were asked to lift up the weight stimuli during their observation of the four exhibits. In the uncued condition, participants observed the exhibits without touching the weight stimuli. After observation of the exhibits, the participants responded to a questionnaire that measured their impressions of the exhibits and the museum, and performed a recognition test on the exhibits. Results showed that memory performance was better and viewing duration was longer with weight lifting instruction than without instruction. A factor analysis on the questionnaires revealed four factors (likeability, contentment, value, and quality). A path analysis showed indirect effects of viewing duration on memory performance and willingness-to-pay (WTP) for the museum appreciation through the impression factors. Our findings provide insight into a new interactive exhibition that enables long appreciation producing positive effects on visitors' impression, memory, and value estimation for exhibits.

The difference in speed sequence influences perceived duration.

Perceived duration of a moving stimulus increases with the speed of the motion. However, a recent study found that the perceived duration of a decelerating stimulus was longer than that of an accelerating one, even though their averaged speed was identical (Matthews 2011 Journal of Experimental Psychology: Human Perception and Performance 37 1617-1627). We conducted three experiments to discover how this speed-change-induced time distortion occurs. We found that the perceived duration of a decelerating motion was longer than that of an accelerating one both in sub-second and supra-second presentation duration conditions, when speed changed linearly over time (experiment 1). The differences could not be explained by the differences in average perceived speed between them (experiment 2). Moreover, the perceived duration of a decelerating motion was also longer than that of an accelerating one, even when speed changed once during the presentation duration (experiment 3). These results suggest that average speed differences in the early and late parts of the presentation duration are important for the occurrence of the speed-change-induced time distortion.

Emotional sounds influence vertical vection.

While viewing a large vertically moving sinusoidal luminance grating, the perception of upward self-motion (vection) was modulated by positive sounds (e.g., a baby's laughter). This may be because positive emotion and the spatial metaphor of vertical directions were unified in the mind.

One's own name distorts visual space.

Here, we demonstrated that one's own name attracts the subjective location of a visual target. We simultaneously presented observers their own name and others' name in the left and right visual fields. A target circle was presented for 53 ms around the center of the display 200 ms after the names disappeared. Ten observers were required to manually reproduce the target location by pointing with the mouse. The results indicated that the observers significantly mislocalized the target 1.61' on average toward the location of their own name. These observations indicated that the visual space is distorted by one's own name, which biases the spatial distribution of visual attention.

Time dilation caused by static images with implied motion.

The present study examined whether implicit motion information from static images influences perceived duration of image presentation. In Experiments 1 and 2, we presented observers with images of a human and an animal character in running and standing postures. The results revealed that the perceived presentation duration of running images was longer than that of standing images. In Experiments 3 and 4, we used abstract block-like images that imitated the human figures used in Experiment 1, presented with different instructions to change the observers' interpretations of the stimuli. We found that the perceived duration of the block image presented as a man running was longer than that of the image presented as a man standing still. However, this effect diminished when the participants were told the images were green onions (objects with no implied motion), suggesting that the effect of implied motion cannot be attributed to low-level visual differences. These results suggest that implied motion increases the perceived duration of image presentation. The potential involvement of higher-order motion processing and the mirror neuron system is discussed.

Perceived duration of plaid motion increases with pattern speed rather than component speed.

Several studies have shown that visual motion distorts perceived duration: The duration of fast-moving stimuli is judged to be longer than the same duration of stationary or slow-moving stimuli. However, it is still unclear which stages of motion processing are involved in this apparent dilation of the perceived duration. In this study, using a two-dimensional pattern motion of a plaid as a stimulus, we systematically manipulated the speed of pattern and component motions of the plaid to examine which motion information influences the perceived duration of the plaid stimuli. Experiment 1 found that perceived duration increased with pattern speed, even though component speed was constant. Experiments 2 and 3 revealed that perceived duration was unchanged, even though component speed increased, as long as the pattern speed was identical. Experiment 4 used both static and moving plaids and confirmed that the results of Experiments 1-3 reflected duration dilation, not duration compression, induced by motion. These results suggest that higher order visual processing in the middle temporal area may play an important role in motion-induced duration dilation.