Radiomics and dosiomics for predicting complete response to definitive chemoradiotherapy patients with oesophageal squamous cell cancer using the hybrid institution model.

OBJECTIVES: To develop a multi-institutional prediction model to estimate the local response to oesophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy based on radiomics and dosiomics features. METHODS: The local responses were categorised into two groups (incomplete and complete). An external validation model and a hybrid model that the patients from two institutions were mixed randomly were proposed. The ESCC patients at stages I-IV who underwent chemoradiotherapy from 2012 to 2017 and had follow-up duration of more than 5 years were included. The patients who received palliative or pre-operable radiotherapy and had no FDG PET images were excluded. The segmentations included the GTV, CTV, and PTV which are used in treatment planning. In addition, shrinkage, expansion, and shell regions were created. Radiomic and dosiomic features were extracted from CT, FDG PET images, and dose distribution. Machine learning-based prediction models were developed using decision tree, support vector machine, k-nearest neighbour (kNN) algorithm, and neural network (NN) classifiers. RESULTS: A total of 116 and 26 patients enrolled at Centre 1 and Centre 2, respectively. The external validation model exhibited the highest accuracy with 65.4% for CT-based radiomics, 77.9% for PET-based radiomics, and 72.1% for dosiomics based on the NN classifiers. The hybrid model exhibited the highest accuracy of 84.4% for CT-based radiomics based on the kNN classifier, 86.0% for PET-based radiomics, and 79.0% for dosiomics based on the NN classifiers. CONCLUSION: The proposed hybrid model exhibited promising predictive performance for the local response to definitive radiotherapy in ESCC patients. CLINICAL RELEVANCE STATEMENT: The prediction of the complete response for oesophageal cancer patients may contribute to improving overall survival. The hybrid model has the potential to improve prediction performance than the external validation model that was conventionally proposed. KEY POINTS: • Radiomics and dosiomics used to predict response in patients with oesophageal cancer receiving definitive radiotherapy. • Hybrid model with neural network classifier of PET-based radiomics improved prediction accuracy by 8.1%. • The hybrid model has the potential to improve prediction performance.

Comparison of clinical outcome between surgical treatment and particle beam therapy for pelvic bone sarcomas: A retrospective multicenter study in Japan.

BACKGROUND: Few studies have compared the clinical outcomes of patients with pelvic bone sarcomas treated surgically and those treated with particle beam therapy. This is a multicenter retrospective cohort study which compared the clinical outcomes of patients with pelvic bone sarcoma who underwent surgical treatment and particle beam therapy in Japan. METHODS: A total of 116 patients with pelvic bone sarcoma treated at 19 specialized sarcoma centers in Japan were included in this study. Fifty-seven patients underwent surgery (surgery group), and 59 patients underwent particle beam therapy (particle beam group; carbon-ion radiotherapy: 55 patients, proton: four patients). RESULTS: The median age at primary tumor diagnosis was 52 years in the surgery group and 66 years in the particle beam group (P < 0.001), and the median tumor size was 9 cm in the surgery group and 8 cm in the particle beam group (P = 0.091). Overall survival (OS), local control (LC), and metastasis-free survival (MFS) rates were evaluated using the Kaplan-Meier method and compared among 116 patients with bone sarcoma (surgery group, 57 patients; particle beam group, 59 patients). After propensity score matching, the 3-year OS, LC, and MFS rates were 82.9% (95% confidence interval [CI], 60.5-93.2%), 66.0% (95% CI, 43.3-81.3%), and 78.4% (95% CI, 55.5-90.5%), respectively, in the surgery group and 64.9% (95% CI, 41.7-80.8%), 86.4% (95% CI, 63.3-95.4%), and 62.6% (95% CI, 38.5-79.4%), respectively, in the particle beam group. In chordoma patients, only surgery was significantly correlated with worse LC in the univariate analysis. CONCLUSIONS: The groups had no significant differences in the OS, LC, and MFS rates. Among the patients with chordomas, the 3-year LC rate in the particle beam group was significantly higher than in the surgery group.

The TIGD5 gene located in 8q24 and frequently amplified in ovarian cancers is a tumor suppressor.

Ovarian cancer (OC) is the fifth most common cancer of female cancer death and leading cause of lethal gynecological cancers. High-grade serous ovarian carcinoma (HGSOC) is an aggressive malignancy that is rapidly fatal. Many cases of OC show amplification of the 8q24 chromosomal region, which contains the well-known oncogene MYC. Although MYC amplification is more frequently observed in OCs than in other tumor types, due to the large size of the 8q24 amplicon, the functions of the vast majority of the genes it contains are still unknown. The TIGD5 gene is located at 8q24.3 and encodes a nuclear protein with a DNA-binding motif, but its precise role is obscure. We show here that TIGD5 often co-amplifies with MYC in OCs, and that OC patients with high TIGD5 mRNA expression have a poor prognosis. However, we also found that TIGD5 overexpression in ovarian cancer cell lines unexpectedly suppressed their growth, adhesion, and invasion in vitro, and also reduced tumor growth in xenografted nude mice in vivo. Thus, our work suggests that TIGD5 may in fact operate as a tumor suppressor in OCs rather than as an oncogene.

Longitudinal changes in depressive symptoms associated with social isolation after the Great East Japan Earthquake in Iwate Prefecture: findings from the TMM CommCohort study.

BACKGROUND: Whether past disaster experiences affect the association between changes in social isolation and depressive symptoms is largely unknown. This study examined the association between changes in social isolation and depressive symptoms among survivors who experienced earthquake damage in the aftermath of the Great East Japan Earthquake (GEJE). METHODS: We analyzed longitudinal data from 10,314 participants who responded to self-report questionnaires on the Lubben Social Network Scale-6 (LSNS-6) and the Center for Epidemiological Studies-Depressive Scale (CES-D) in both the baseline survey (FY2013 to FY2015) and follow-up survey (FY2017 to FY2019) after the GEJE. According to changes in the presence of social isolation (< 12 of LSNS-6) at two time points, participants were categorized into four groups: "not socially isolated," "improved socially isolated," "newly socially isolated," and "continuously socially isolated." At the follow-up survey, a CES-D score of ≥ 16 indicates the presence of depressive symptoms. The adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were estimated using the logistic regression analysis to examine the influence of the change in social isolation over four years on depressive symptoms. RESULTS: Participants who were newly socially isolated had a significantly higher prevalence of depressive symptoms than those who were not socially isolated (AOR = 1.89, 95% CI = 1.61 - 2.23). In addition, AORs were highest for those who were continuously socially isolated and had experienced house damage (AOR = 2.17, 95% CI = 1.73 - 2.72) and those who were newly socially isolated and had not experienced the death of family members due to the GEJE (AOR = 1.88, 95%CI = 1.60 - 2.22). CONCLUSION: Our longitudinal findings suggest that being newly or continuously socially isolated is associated with a risk of depressive symptoms, not only among those who had experienced house damage or the death of a family member, but also those who had not, in the disaster-affected area. Our study underlines the clinical importance of social isolation after a large-scale natural disaster and draws attention to the need for appropriate prevention measures.

[Environmental risks to housing and living arrangements among older survivors of the Great East Japan Earthquake and their relationships with housing type: The RIAS Study].

Objective　Over the course of their lives, people spend most of their time in the home environment. The Community-based Integrated Care System 2018 by the Ministry of Health, Labour and Welfare in Japan declared the importance of "housing" and "living arrangements" as essential elements to enable older adults to live independently and to protect their privacy and dignity in their communities. The present study aims to clarify the relationship between current housing type and "housing" and "living arrangements" among older survivors of the Great East Japan Earthquake (GEJE).Methods　We used data obtained from 3,856 participants, aged 65 years or older, in the Research project for prospective Investigation of health problems Among Survivors of the GEJE (RIAS). Housing types were categorized as follows: "same housing," "temporary housing," "disaster public housing," "new housing" (in a different area), and "others." Healthy housing scores were calculated using a housing health checklist from the Nationwide Smart Wellness Housing Survey in Japan. "Living arrangements" were assessed based on residential status, social network, and social capital. To determine the risks associated with each "housing" and "living arrangement" category, we used multivariate logistic and linear regression models.Results　The number of participants in each housing type was as follows: 2,531 in "same housing," 146 in "temporary housing," 234 in "disaster public housing," 844 in "new housing," and 101 in "others." Compared with those living in "same housing," those living in "disaster public housing," "new housing," and "others" had a significantly higher healthy housing score, whereas those living in "temporary housing" had a lower score. However, with regards to "living arrangements," the number of residents who were living alone was significantly higher among those in "disaster public housing," and those living in "disaster public housing" as well as "new housing" had low social capital compared with those living in "same housing." The likelihood of having a poor social network was substantially higher for those living in "disaster public housing." Sub-scale analyses indicated that "disaster public housing" was associated with less family support, whereas "new housing" was associated with less support from friends.Conclusion　The present results indicate that older survivors-regardless of whether they live in the existing community-find it challenging to establish new social capital and social networks in a new location without the presence of "someone" they knew before the disaster.

Psychological Distress in Responders and Nonresponders in a 5-year Follow-up Health Survey: The RIAS Study.

BACKGROUND: People with poor health or mental conditions are generally unwilling to participate in the health examinations, and no studies have directly examined the relationship of psychological distress among disaster survivors with participation status to date. The present study thus examined psychosocial differences according to the respondent status in a 5-year follow-up survey among participants in the prospective health surveys on survivors of the Great East Japan Earthquake and Tsunami Disaster study in Iwate Prefecture, Japan. METHODS: We analyzed data from 10,203 Japanese survivors aged ≥18 years (mean age, 65.6 years; 38.0% men) and who underwent health examinations at baseline in 2011. Participants were classified into responders and nonresponders according to their 2015 health examination participation status. Psychological distress was evaluated using the Kessler 6 scale and categorized as none, mild, and severe. Multinominal logistic regression was used to examine the risk of psychological distress in relation to participation status. RESULTS: In the 2015 survey, 6,334 of 6,492 responders and 1,686 of 3,356 nonresponders were analyzed. The most common reasons for nonparticipation in the survey were participated in other health examinations, examined at a hospital, and did not have time to participate. Nonresponse in males was associated only with mild psychological stress, whereas nonresponse in females was associated with mild and severe psychological distress. CONCLUSION: Nonresponders in the follow-up survey had a higher risk of psychological distress than responders. Continuous monitoring of the health of nonresponders and responders may help to prevent future health deterioration.

Combined Associations of Liver Enzymes and Obesity With Diabetes Mellitus Prevalence: The Tohoku Medical Megabank Community-based Cohort Study.

BACKGROUND: Alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) are enzymes associated with diabetes mellitus (DM) prevalence. However, limited information is available regarding the association of liver enzymes and DM consistently present in obese and non-obese individuals. We examined whether the combination of ALT and GGT enzymes is associated with the prevalence of DM, regardless of obesity, in a general Japanese population. METHODS: We conducted a cross-sectional study of 62,786 participants aged ≥20 years who lived in Miyagi and Iwate, Japan. We divided all the participants into eight groups according to the ALT level (low: <30 IU/L and high: ≥30 IU/L), GGT level (low: <50 IU/L and high: ≥50 IU/L), and the presence of obesity. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression analysis, adjusting for potential confounders, to determine associations of the combination of ALT and GGT levels and obesity with DM prevalence. RESULTS: Overall, 6,008 participants (9.6%) had DM. Compared to non-obese individuals with low ALT and GGT levels, the participants with high ALT and GGT levels had high ORs for DM in both obese (OR 4.06; 95% CI, 3.61-4.56) and non-obese groups (OR 2.19; 95% CI, 1.89-2.52). The obese group had high ORs for DM, even at low ALT and GGT levels. CONCLUSION: High ALT and GGT levels are associated with DM prevalence in obese and non-obese participants. This finding suggests that correcting ALT and GGT levels and controlling obesity are important for the prevention of DM.

Space-Making Particle Therapy for Unresectable Hilar Cholangiocarcinoma.

INTRODUCTION: Although the primary treatment option for hilar cholangiocarcinoma (HC) has been surgical resection, most patients present with unresectable advanced tumors at the time of diagnosis. Particle therapy (PT) holds great potential for HC, even though the anatomical proximity to the gastrointestinal tract prevents delivering a radical dose to the tumor. Space-making PT (SMPT), consisting of spacer placement surgery and subsequent PT, has been developed to minimize complications and maximize the therapeutic benefit of dose escalation for HC. This study aimed to conduct a dosimetric evaluation and examine the effectiveness of SMPT for the treatment of HC. METHODS: Between 2007 and 2018, 12 patients with unresectable HC treated with SMPT were enrolled. The treatment outcomes and effectiveness of spacer placement surgery were evaluated through analyses of pre- and post-surgical parameters of dose-volume histograms. RESULTS: All patients completed the planned SMPT protocol. The median survival time was 29.6 months, and the 1- and 3-year overall survival rates were 82.5% and 45.8%, respectively. The mean V95% value (volume irradiated with 95% of the planned treatment dose) of the gross tumor volume and clinical target volume after spacer placement surgery improved to 98.5% and 96.6% from preoperative values of 85.6% and 78.1%, respectively (p = 0.0196 and p = 0.0053, respectively). Grade 3 or higher adverse events after SMPT were seen in 6 patients. DISCUSSION/CONCLUSION: SMPT led to improvements in dosimetric parameters and showed good feasibility and excellent outcomes. SMPT can be a promising novel alternative for unresectable HC.

Phase I trial of concurrent chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF-CRT) for locally advanced squamous cell carcinoma of the external auditory canal.

PURPOSE: Chemoradiotherapy with docetaxel (DOC), cisplatin (CDDP), and 5-FU (TPF-CRT) for locally advanced external auditory canal cancer (EACC) has favorable oncological and functional outcomes. To establish TPF-CRT as a standard of care for advanced EACC, we conducted this study to determine the maximum tolerated (MTD) and recommended dose (RD) of DOC in TPF-CRT for locally advanced EACC. METHODS: To determine the recommended (RD) and maximum tolerated dose (MTD) of DOC in TPF-CRT for EACC, a phase I trial was conducted using the standard "3 + 3" design for maximum dose finding. DOC was administered twice every 4 weeks, CDDP at 70 mg/m2 and 5-FU at 700 mg/m2; patients were also receiving radiotherapy (66 Gy). Eight patients with T3 or T4 EACC were prospectively enrolled. RESULTS: Two patients treated with DOC, 50 mg/m2, and one out of six patients treated with DOC, 40 mg/m2, had dose-limiting toxicities. Prolonged febrile neutropenia was observed in three patients. Grade 3 non-hematological toxicities were observed in only three patients. At study completion, six patients survived, five of whom were disease free. CONCLUSION: The RD and MTD of DOC in TPF-CRT for locally advanced EACC are 40 mg/m2 when doses of CDDP and 5-FU are 70 mg/m2 and 700 mg/m2, respectively.

Fiducial marker position affects target volume in stereotactic lung irradiation.

PURPOSE: Real-time tracking systems of moving respiratory targets such as CyberKnife, Radixact, or Vero4DRT are an advanced robotic radiotherapy device used to deliver stereotactic body radiotherapy (SBRT). The internal target volume (ITV) of lung tumors is assessed through a fiducial marker fusion using four-dimensional computed tomography (CT). It is important to minimize the ITV to protect normal lung tissue from exposure to radiation and the associated side effects post SBRT. However, the ITV may alter if there is a change in the position of the fiducial marker with respect to the tumor. This study investigated the relationship between fiducial marker position and the ITV in order to prevent radiation exposure of normal lung tissue, and correct target coverage. MATERIALS AND METHODS: This study retrospectively reviewed 230 lung cancer patients who received a fiducial marker for SBRT between April 2015 and September 2021. The distance of the fiducial marker to the gross tumor volume (GTV) in the expiratory (dex ) and inspiratory (din ) CT, and the ratio of the ITV/V(GTVex ), were investigated. RESULTS: Upon comparing each lobe, although there was no significant difference in the ddiff and the ITV/V(GTVex ) between all lobes for dex  < 10 mm, there was significant difference in the ddiff and the ITV/V(GTVex ) between the lower and upper lobes for dex ≥ 10 mm (p < 0.05). Moreover, there was significant difference in the ddiff and the ITV/V(GTVex ) between dex ≥10 mm and dex  < 10 mm in all lung regions (p < 0.05). CONCLUSION: The ITV that had no margin from GTVs increased when dex was ≥10 mm for all lung regions (p < 0.05). Furthermore, the increase in ITV tended to be greater in the lower lung lobe. These findings can help decrease the possibility of adverse events post SBRT, and correct target coverage.

Study Profile of the Tohoku Medical Megabank Community-Based Cohort Study.

BACKGROUND: We established a community-based cohort study to assess the long-term impact of the Great East Japan Earthquake on disaster victims and gene-environment interactions on the incidence of major diseases, such as cancer and cardiovascular diseases. METHODS: We asked participants to join our cohort in the health check-up settings and assessment center based settings. Inclusion criteria were aged 20 years or over and living in Miyagi or Iwate Prefecture. We obtained information on lifestyle, effect of disaster, blood, and urine information (Type 1 survey), and some detailed measurements (Type 2 survey), such as carotid echography and calcaneal ultrasound bone mineral density. All participants agreed to measure genome information and to distribute their information widely. RESULTS: As a result, 87,865 gave their informed consent to join our study. Participation rate at health check-up site was about 70%. The participants in the Type 1 survey were more likely to have psychological distress than those in the Type 2 survey, and women were more likely to have psychological distress than men. Additionally, coastal residents were more likely to have higher degrees of psychological distress than inland residents, regardless of sex. CONCLUSION: This cohort comprised a large sample size and it contains information on the natural disaster, genome information, and metabolome information. This cohort also had several detailed measurements. Using this cohort enabled us to clarify the long-term effect of the disaster and also to establish personalized prevention based on genome, metabolome, and other omics information.

Association between the social isolation and depressive symptoms after the great East Japan earthquake: findings from the baseline survey of the TMM CommCohort study.

BACKGROUND: Social isolation and mental health issues have become a severe problem in disaster areas in the Great East Japan Earthquake. This study examined whether the combination of the house damage and social isolation or the combination of the death of family members and social isolation is associated with depressive symptoms among survivors using the baseline study data of the Tohoku Medical Megabank Project Community-Based Cohort Study (TMM CommCohort Study). METHODS: We used cross-sectional data from a baseline survey of 48,958 participants (18,423 males, 30,535 females; aged 60.1 ± 11.2 years) to examine the association between social isolation measured by the Lubben social network scale 6 (LSNS-6) and depressive symptoms measured by the Center for Epidemiological Studies-Depressive Scale (CES-D). The presence of social isolation and depressive symptoms was defined by an LSNS-6 score of < 12 and a CES-D score of ≥16, respectively. We performed a logistic regression analysis to determine the multivariable-adjusted odds ratio (95% confidence interval) [AOR (95% CI)] for depressive symptoms according to sex in the social isolation in comparison to without social isolation, and the associations of the combination of the house damage or the death of family members and social isolation and depressive symptoms. RESULTS: Social isolation was significantly associated with depressive symptoms (males: OR = 1.87; 95% CI = 1.72-2.04, females: OR = 2.13; 95% CI = 2.00-2.26). Both males and females respondents with severe house damage and social isolation had a greater risk of depressive symptoms in comparison to those with an undamaged house and without social isolation (males: OR = 3.40; 95% CI = 2.73-4.24, females: OR = 2.92; 95% CI = 2.46-3.46). The risk of depressive symptoms was also higher in both males and females respondents with the death of family members and social isolation in comparison to those without the death of family members and without social isolation (males: OR = 2.18; 95% CI = 1.90-2.50, females: OR = 2.60; 95% CI = 2.35-2.88). CONCLUSION: The findings suggested that a combination of social isolation and severe house damage and the death of family members caused by a large-scale natural disaster was associated with a higher risk of depressive symptoms although the interaction was not statistically significant.

[Falls and associated risk factors among elderly survivors of the Great East Japan Earthquake: RIAS Study].

Objective　An increasing incidence of disuse syndrome is commonly observed in areas affected by large-scale natural disasters. Consequently, the fall risk is high in such populations, necessitating adequate attention to fall prevention measures. It is important to identify factors associated with falls to prevent deterioration in functional ability. We investigated the risk factors associated with falls among elderly survivors in disaster-stricken areas using longitudinal data from the Research project for the prospective Investigation of health problems Among Survivors of the Great East Japan Earthquake (RIAS) Study.Methods　Of all data obtained from the RIAS Study, we used the data of 1,380 survivors who were aged ≥65 years, were not diagnosed with cancer or cardiovascular disease, did not need supportive care, and could participate in the annual survey between 2011 and 2016. Self-administered questionnaires were distributed, and anthropometric and grip tests were performed during the 2011 survey to obtain information regarding housing damage, the fear of falls, arthralgia, cognitive function psychological distress, insomnia, frequency of leaving the house, a history of hypertension, dyslipidemia, diabetes, alcohol consumption status, smoking status, and/or body mass index, and grip strength. Based on the responses obtained from each annual survey, a fall was defined as an event during which an individual had fallen at least once. Multivariate-adjusted odds ratio(OR) and 95% confidence interval(CI) for all variables related to falls were calculated using logistic regression with adjustment for sex and residential area. Similar analyses were performed based on age groups (65-74 years and ≥75 years).Results　The 5-year fall incidence rate was 35.5% (31.9% [men], 37.9% [women]). In men, cognitive dysfunction was significantly associated with falls (OR 1.50, 95%CI 1.01-2.22). In women, cognitive dysfunction (OR 1.82, 95%CI 1.34-2.47), insomnia (OR 1.41, 95%CI 1.02-1.94), dyslipidemia (OR 1.58, 95% 95% CI 1.11-2.25), and a history of smoking (OR 4.30, 95%CI 1.08-17.14) were significantly associated with falls. In women aged ≥75 years, partial housing damage (OR 7.93, 95%CI 1.85-33.91) and psychological distress (OR 2.83, 95%CI 1.09-.7.37) were also significantly associated with falls.Conclusion　This study suggests that cognitive dysfunction in both sexes and insomnia, dyslipidemia, and a history of smoking in women were significantly associated with falls, and partial housing damage and psychological distress were risk factors for falls in women aged ≥75 years. Fall prevention after large-scale natural disasters warrants close attention to known risk factors and environmental and mental health changes.

Antibody-Conjugated Signaling Nanocavities Fabricated by Dynamic Molding for Detecting Cancers Using Small Extracellular Vesicle Markers from Tears.

Small extracellular vesicles (sEVs) are reliable biomarkers for early cancer detection; however, conventional detection methods such as immune-based assays and microRNA analyses are not very sensitive and require sample pretreatments and long analysis time. Here, we developed a molecular imprinting-based dynamic molding approach to fabricate antibody-conjugated signaling nanocavities capable of size recognition. This enabled the establishment of an easy-to-use, rapid, sensitive, pretreatment-free, and noninvasive sEV detection platform for efficient sEV detection-based cancer diagnosis. An apparent dissociation constant was estimated to be 2.4 × 10-16 M, which was ∼1000 times higher than that of commercial immunoassays (analysis time, 5 min/sample). We successfully used tears for the first time to detect cancer-related intact sEVs, clearly differentiating between healthy donors and breast cancer patients, as well as between samples collected before and after total mastectomy. Our nanoprocessing strategy can be easily repurposed for the specific detection of other types of cancer by changing the conjugated antibodies, thereby facilitating the establishment of liquid biopsy for early cancer diagnosis.

Poor self-rated health predicts the incidence of functional disability in elderly community dwellers in Japan: a prospective cohort study.

BACKGROUND: Although previous large population studies showed elderly with poor self-rated health (SRH) to be at a high risk of functional disability in Western countries, there have been few studies in which the association between SRH and functional disability was investigated in Japanese community dwellers. The association between SRH and functional disability, defined as certification of the long-term care insurance (LTCI) system, in Japanese elderly community dwellers was examined in this study. METHODS: A total of 10,690 individuals (39.5% men, mean age of 71.4 years) who were 65 years of age or more who did not have a history of cardiovascular disease or LTCI certification were followed in this prospective study for 10.5 years. SRH was classified into four categories: good, rather good, neither good nor poor, and poor. A Cox proportional-hazards model was used to determine the hazard ratios (HRs) for the incidence of functional disability among the SRH groups for each sex. RESULTS: The number of individuals with functional disability was 3377. Men who rated poor for SRH scored significantly higher for functional disability (HR [95% confidence interval]: poor = 1.74 [1.42, 2.14]) while women who rated rather good, neither good nor poor, and poor scored significantly higher for functional disability (rather good =1.12 [1.00, 1.25], neither good nor poor = 1.29 [1.13, 1.48], poor = 1.92 [1.65, 2.24]: p for trend < 0.001 in both sexes). CONCLUSION: Self-rated health, therefore, might be a useful predictor of functional disability in elderly people.

Phase 1/2 study of concurrent chemoradiotherapy with weekly irinotecan hydrochloride for advanced/recurrence uterine cancer: A multi-institutional study of Kansai Clinical Oncology Group.

OBJECTIVE: Concurrent chemoradiotherapy using cisplatin was thought to be standard treatment for squamous cell carcinoma of cervix, but it had not been effective for adenocarcinoma. Concurrent chemoradiotherapy using irinotecan hydrochloride (CPT-11) had been effective for colorectal cancer, thus, we chose CPT-11 as a candidate for gynecologic adenocarcinoma. To evaluate the maximum tolerated dose (MTD) of weekly CPT-11 with external pelvic radiotherapy, a phase 1/2 study was conducted according to modified Fibonacci method. METHODS: Eligible patients were advanced uterine cancer with measurable diseases [performance score (PS): 0-2]. Study period was from August 1st, 2002 to December 31st, 2008. The starting dose level (DL) of CPT-11 was 30 mg/m2 (DL1) given weekly for 4 weeks. Subsequently, dose escalation was scheduled in 10 mg/m2 increments to 60 mg/m2 (DL4). The fixed radiotherapy consisted of whole pelvic 1.8 Gy/d, once a day in weekday for five weeks and it amounted to 45 Gy (25 fractions) in total. RESULTS: Seventeen patients were enrolled. As for toxicities, one (1/17: 5.9%) grade (G) 4 neutropenia lasting 7 days had been seen in DL4. G2 diarrhea was identified in 35.3% (6/17) of the patients, and 11.8% (2/17) G3 diarrhea was observed in DL3 and DL4. Thus, the MTD of CPT-11 was defined as dose of 60 mg/m2. The recommended dose was decided as 50 mg/m2. The response rate was 88.2% [9 complete response (CR), 3 partial response (PR), 3 stable disease (SD), 2 not evaluable (NE)]. Disease control rate at 1 month after treatment completion was 100% but distant metastases were found in 24% (4/17) in longer outcome. CONCLUSIONS: MTD was 60 mg/m2 and recommended dose was set as 50 mg/m2. This concurrent chemoradiation using weekly CPT-11 was feasible at 50 mg/m2, and it might be effective even in adenocarcinoma of the uterus.

Patient preference study comparing hypofractionated versus conventionally fractionated whole-breast irradiation after breast-conserving surgery.

OBJECTIVE: To compare patient preferences and acute adverse events of hypofractionated (HF) and conventionally fractionated (CF) whole-breast irradiation (WBI) after breast-conserving surgery in our institution. METHODS: We conducted a patient preference study comparing CF-WBI (50 Gy/25 fractions) and HF-WBI (41.6 Gy/16 fractions) after breast-conserving surgery. Eligible patients selected either type of fractionation following an explanation from the radiation oncologist. In this report, we analyzed the selection rate and acute toxicities. RESULTS: Between June 2009 and December 2013, 348 patients (349 breasts) were identified as eligible for the study. Among them, 259 patients (260 breasts [74.5%]) selected CF-WBI and 89 patients (89 breasts [25.5%]) selected HF-WBI. Factors significantly associated with the selection of HF-WBI were older age (P = 0.028) and no adjuvant chemotherapy (P = 0.041). Regarding acute adverse events, Grade 2 (G2) or higher radiation dermatitis was less frequently observed in HF-WBI than in CF-WBI (13.8% vs. 29.4%; P = 0.004). In addition, G2 or higher breast pain was only observed in the CF-WBI group (6.9%; P = 0.012). There were no significant differences in the presence of fatigue, wound pain or radiation pneumonitis of G2 or higher between the groups. CONCLUSIONS: In this study, in which patients themselves selected the irradiation method, more patients tended to select CF-WBI. The frequency of G2 or higher dermatitis and breast pain was significantly lower in the HF-WBI group than in the CF-WBI group. Our results support the evidence for recommending HF-WBI after breast-conserving surgery while presenting aspects of patient preferences.

A Pretreatment-Free, Polymer-Based Platform Prepared by Molecular Imprinting and Post-Imprinting Modifications for Sensing Intact Exosomes.

Exosomes are small (30-100 nm) membrane vesicles that serve as regulatory agents for intercellular communication in cancers. Currently, exosomes are detected by immuno-based assays with appropriate pretreatments like ultracentrifugation and are time consuming (>12 h). We present a novel pretreatment-free fluorescence-based sensing platform for intact exosomes, wherein exchangeable antibodies and fluorescent reporter molecules were aligned inside exosome-binding cavities. Such antibody-containing fluorescent reporter-grafted nanocavities were prepared on a substrate by well-designed molecular imprinting and post-imprinting modifications to introduce antibodies and fluorescent reporter molecules only inside the binding nanocavities, enabling sufficiently high sensitivity to detect intact exosomes without pretreatment. The effectiveness of the system was demonstrated by using it to discriminate between normal exosomes and those originating from prostate cancer and analyze exosomes in tear drops.

Retrospective assessment of a single fiducial marker tracking regimen with robotic stereotactic body radiation therapy for liver tumours.

AIM: To investigate tumour motion tracking uncertainties in the CyberKnife Synchrony system with single fiducial marker in liver tumours. BACKGROUND: In the fiducial-based CyberKnife real-time tumour motion tracking system, multiple fiducial markers are generally used to enable translation and rotation corrections during tracking. However, sometimes a single fiducial marker is employed when rotation corrections are not estimated during treatment. MATERIALS AND METHODS: Data were analysed for 32 patients with liver tumours where one fiducial marker was implanted. Four-dimensional computed tomography (CT) scans were performed to determine the internal target volume (ITV). Before the first treatment fraction, the CT scans were repeated and the marker migration was determined. Log files generated by the Synchrony system were obtained after each treatment and the correlation model errors were calculated. Intra-fractional spine rotations were examined on the spine alignment images before and after each treatment. RESULTS: The mean (standard deviation) ITV margin was 4.1 (2.3) mm, which correlated weakly with the distance between the fiducial marker and the tumour. The mean migration distance of the marker was 1.5 (0.7) mm. The overall mean correlation model error was 1.03 (0.37) mm in the radial direction. The overall mean spine rotations were 0.27° (0.31), 0.25° (0.22), and 0.23° (0.26) for roll, pitch, and yaw, respectively. The treatment time was moderately associated with the correlation model errors and weakly related to spine rotation in the roll and yaw planes. CONCLUSIONS: More caution and an additional safety margins are required when tracking a single fiducial marker.

Myo-inositol concentration in MR spectroscopy for differentiating high grade glioma from primary central nervous system lymphoma.

It is sometimes difficult to distinguish gliomas from other tumors on routine imaging. In this study, we assessed whether 3-T magnetic resonance spectroscopy (MRS) with LCModel software might be useful for discriminating glioma from other brain tumors, such as primary central nervous system lymphomas (PCNSLs) and metastatic tumors. A total of 104 cases of brain tumor (66 gliomas, 20 PCNSLs, 6 metastatic tumors, 12 other tumors) were preoperatively investigated with short echo time (35 ms) single-voxel 3-T MRS. LCModel software was used to evaluate differences in the absolute concentrations of choline, N-acetylaspartate, N-acetylaspartylglutamate, glutamate + glutamine, myo-inositol (mIns), and lipid. mIns levels were significantly increased in high-grade glioma (HGG) compared with PCNSL (p < 0.001). In multivariate logistic regression analysis, mIns was the best marker for differentiating HGG from PCNSL (p < 0.0001, odds ratio 1.9927, 95% confidence interval 1.3628-3.2637). Conventional MRS detection of mIns resulted in a high diagnostic accuracy (sensitivity, 64%; specificity, 90%; area under the receiver operator curve, 0.80) for HGG. The expression of inositol 3-phosphate synthase (ISYNA1) was significantly higher in gliomas than in PCNSLs (p < 0.05), suggesting that the increased level of mIns in glioma is due to high expression of ISYNA1, the rate-limiting enzyme in the mIns-producing pathway. In conclusion, noninvasive analysis of mIns using single-voxel MRS may be useful in distinguishing gliomas from other brain tumors, particularly PCNSLs.