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BackgroundPhosphatidylinositol 3-kinase (PI3K) pathway activation is a hallmark of endocrine therapy-resistant, hormone receptor-positive breast cancer. This phase 3 study assessed the efficacy of the pan-PI3K inhibitor buparlisib plus fulvestrant in patients with advanced breast cancer, including an evaluation of the PI3K pathway activation status as a biomarker for clinical benefit.MethodsThe BELLE-2 trial was a randomised, double-blind, placebo-controlled, multicentre study. Postmenopausal women aged 18 years or older with histologically confirmed, hormone receptor-positive and human epidermal growth factor (HER2)-negative inoperable locally advanced or metastatic breast cancer whose disease had progressed on or after aromatase inhibitor treatment and had received up to one previous line of chemotherapy for advanced disease were included. Eligible patients were randomly assigned (1:1) using interactive voice response technology (block size of 6) on day 15 of cycle 1 to receive oral buparlisib (100 mg/day) or matching placebo, starting on day 15 of cycle 1, plus intramuscular fulvestrant (500 mg) on days 1 and 15 of cycle 1, and on day 1 of subsequent 28-day cycles. Patients were assigned randomisation numbers with a validated interactive response technology; these numbers were linked to different treatment groups which in turn were linked to treatment numbers. PI3K status in tumour tissue was determined via central laboratory during a 14-day run-in phase. Randomisation was stratified by PI3K pathway activation status (activated vs non-activated vs and unknown) and visceral disease status (present vs absent). Patients, investigators, local radiologists, study team, and anyone involved in the study were masked to the identity of the treatment until unblinding. The primary endpoints were progression-free survival by local investigator assessment per Response Evaluation Criteria In Solid Tumors (version 1.1) in the total population, in patients with known (activated or non-activated) PI3K pathway status, and in PI3K pathway-activated patients. Efficacy analyses were done in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study drug and had at least one post-baseline safety assessment according to the treatment they received. This trial is registered with ClinicalTrials.gov, number NCT01610284, and is currently ongoing but not recruiting participants.FindingsBetween Sept 7, 2012, and Sept 10, 2014, 1147 patients from 267 centres in 29 countries were randomly assigned to receive buparlisib (n=576) or placebo plus fulvestrant (n=571). In the total patient population (n=1147), median progression-free survival was 6·9 months (95% CI 6·8-7·8) in the buparlisib group versus 5·0 months (4·0-5·2) in the placebo group (hazard ratio [HR] 0·78 [95% CI 0·67-0·89]; one-sided p=0·00021). In patients with known PI3K status (n=851), median progression-free survival was 6·8 months (95% CI 5·0-7·0) in the buparlisib group vs 4·5 months (3·3-5·0) in the placebo group (HR 0·80 [95% CI 0·68-0·94]; one-sided p=0·0033). In PI3K pathway-activated patients (n=372), median progression-free survival was 6·8 months (95% CI 4·9-7·1) in the buparlisib group versus 4·0 months (3·1-5·2) in the placebo group (HR 0·76 [0·60-0·97], one-sided p=0·014). The most common grade 3-4 adverse events in the buparlisib group versus the placebo group were increased alanine aminotransferase (146 [25%] of 573 patients vs six [1%] of 570), increased aspartate aminotransferase (103 [18%] vs 16 [3%]), hyperglycaemia (88 [15%] vs one [

Aim: Treatment options for esophageal squamous cell carcinoma includes surgery and chemoradiotherapy (CRT), however there was limited information about the factors influenced in patients' decision-making. Materials & methods: Patients who participated in JCOG0502, a parallel group controlled trial comparing surgery with CRT, were analyzed for the factors related to decision-making. Results: Of the 368 patients (pts) enrolled in the nonrandomized part in JCOG0502, 209 pts opted for surgery and 159 pts chose CRT on their own. Background characteristics were the same except for age. Multivariable logistic regression analysis showed that age ≥65 years, male sex, multiple lesions, absence of children and doctor's thinking were associated with the selection of CRT. Conclusion: The doctor's option was the most influential factor in the patient's decision-making process. Clinical Trial Registration: UMIN000000551 (ClinicalTrials.gov) Article highlights The JCOG0502 was a randomized trial designed to compare surgery and definitive chemoradiotherapy (CRT) in terms of overall survival for clinical stage I esophageal squamous cell carcinoma. However, the patients who did not consent to the randomized part of this trial could select their preferred therapy in a patient-preference arm. The results of the JCOG0502 showed that definitive CRT was noninferior to surgery in the nonrandomized part. Various factors might influence patients' selection of surgery or definitive CRT, but what these factors were remained unclear. From the results of the univariable analysis in the JCOG0502, older age and the doctor's thinking for definitive CRT or both treatments were associated with patients' decision to select definitive CRT. From the results of the multivariable analysis in the JCOG0502, older age, male sex, multiple lesions, absence of children and the doctor's thinking were independent factors for patients' decision to select definitive CRT. In these factors, the doctor's thinking was the factor that most strongly influenced the patient's decision-making. [ABSTRACT FROM AUTHOR]

Background/Objectives: Health management in workers in the taxi industry is particularly challenging due to irregular working hours and the need to prevent fatal accidents. In addition, drivers in Japan are aging, and the early prevention of age-related deterioration in oral health is an increasingly important issue. The aim of this cross-sectional study was to investigate the relationships between oral diadochokinesis (OD), tongue pressure, and lip-seal strength in Japanese male taxi workers. Methods: Measurements of tongue pressure and lip-seal strength were performed by dentists using specialized equipment. OD was measured using the number of consecutive "Pa", "Ta", and "Ka" vocalizations that could be produced in 5 s. We performed multiple regression analysis to examine the effects of lip-seal strength and tongue pressure on OD. Results: The study included 437 participants, excluding 17 who could not complete all oral cavity measurements. Tongue pressure showed a significant positive correlation with "Pa", "Ta", and "Ka" (correlation coefficients: 0.527–0.680). Lip-seal strength was not significantly correlated with OD. Tongue pressure showed a significant positive correlation with "Pa", "Ta", and "Ka". In the results of multiple regression analyses without the elderly participants, tongue pressure was associated with "Pa" (β[95% confidence interval]: 0.574[0.304, 0.843]), "Ta" (0.436[0.231, 0.640]), and "Ka" (0.424[0.210, 0.639]), and lip-seal strength was associated with "Pa" (0.128[0.032, 0.224]) and "Ka" (0.083[0.006, 0.160]). Conclusions: OD may be associated with lip-seal strength and tongue pressure even without including elderly workers. Regardless of age, maintaining good OD may help maintain lip-seal strength and tongue pressure, which may play a role in reducing the risk of age-related oral disorders. [ABSTRACT FROM AUTHOR]

Background: In older patients, esophageal squamous cell carcinoma (ESCC) is difficult to treat using standard therapies, including surgery and cisplatin-based chemoradiotherapy. Paclitaxel (PTX) has radiosensitizing activity. We conducted a phase I trial of PTX combined with radiotherapy to establish a standard therapy for locally advanced ESCC in older patients. Methods: Enrollment was conducted at six centers in Japan from April 2016 to September 2019. The participants were aged ≥ 70 years, had locally advanced ESCC, and were intolerant to surgery or unwilling. A fixed 60-Gy radiation dose was administered in 30 fractions. PTX dosing levels started at 30 mg/m2 weekly for 6 weeks. Depending on the number of DLTs, the dose was set to be increased by 10 mg/m2 or switched to biweekly. A geriatric assessment was performed before treatment using the Geriatric-8 screening tool. The primary endpoint was dose-limiting toxicity (DLT). Results: We enrolled 24 patients (6 per group); DLT was observed in one (grade 4 hypokalemia), one (grade 3 aspiration), two (grade 3 radiodermatitis, grade 3 esophageal hemorrhage), and two (grade 3 anorexia, grade 5 pneumonitis) patients in the weekly PTX 30, 40, 50, and 60 mg/m2 groups, respectively. All adverse events, except death in the 60 mg/m2 group, showed reversible improvement, and the safety profile was considered acceptable. The 2-year survival and complete response rates were 40.0% and 54.2%, respectively. There was a significant difference in survival between favorable and unfavorable Geriatric-8 scores. Conclusions: The recommended PTX dose with concomitant radiation was determined to be 50 mg/m2 weekly. Phase II trials at this dose are underway. [ABSTRACT FROM AUTHOR]

Objective: Reports demonstrating the effectiveness and safety of strut-adjusted volume implants (SAVI) in Japan are limited. Therefore, this study aimed to compare the treatment outcomes of SAVI and whole-breast irradiation (WBI) at a single facility. Materials and Methods: Data were retrospectively extracted from the medical records of patients treated with SAVI or WBI following partial mastectomy (Bp). Patients undergoing Bp, sentinel lymph node biopsy, and SAVI spacer insertion followed by brachytherapy with the SAVI device were compared to those followed with WBI. Local recurrence was assessed annually by physical examination, bilateral mammography, and breast ultrasonography. Results: The SAVI and WBI groups comprised 53 and 113 patients, with a median age of 55 and 52 years, respectively; among them, 47 and 91 patients had a pathological tumor diameter ≤2 cm and six and 22 had a pathological tumor diameter >2 cm, respectively. Recurrence events, acute adverse events, and late adverse events were observed in the SAVI and WBI groups in 1 and 3 (p = 0.726), 24 and 79 (p = 0.01), and 24 and 18 patients (p = 0.00002), respectively, with median observation periods of 60.0 and 47.8 months, respectively. All adverse events were grades 1-2, with dermatitis being the most common in the acute phase. In the late phase, pigmentation was common in both groups. Conclusion: The local recurrence rate does not differ between SAVI and WBI within the relatively short-term follow-up period. Longer follow-up is required to confirm our results in the Japanese population. [ABSTRACT FROM AUTHOR]