Postoperative Late Hearing Deterioration in Cholesteatoma with Labyrinthine Fistulas.

A labyrinthine fistula is a severe complication of middle ear cholesteatoma that can cause profound sensorineural hearing loss and vertigo. However, there is no consensus regarding the transition to postoperative hearing. Although hearing deteriorates gradually with a delay in some cases of labyrinthine fistula, insufficient consideration has been given to this point. We examined perioperative changes in cases of middle ear cholesteatoma with labyrinthine fistulas. We retrospectively reviewed the medical records of 578 patients with middle ear cholesteatoma who underwent tympanoplasty at our hospital between 2016 and 2021. Patients with labyrinthine fistulas were selected; their perioperative bone-conduction hearing was assessed. Fistula depth was determined following the classification reported by Dornhoffer et al. The hearing was compared preoperatively, early postoperatively (3-6 months), and 1 year postoperatively. Forty-eight patients (8.3%) had labyrinthine fistulas. Regarding depth, 21 cases were type I, 14 were type IIa, 3 were type IIb, and 10 were type III. Preoperative bone-conduction hearing was significantly poor in invasion type IIb or deeper cases. Cases with type IIb or deeper fistulas, multiple fistulas, or vertigo deteriorated postoperatively. Type III cases or those with multiple fistulas deteriorated further from the early postoperative period to 1 year postoperatively. Concerning frequency, 500 and 2000 Hz showed a delayed deterioration. This is a valuable report of delayed hearing loss after surgery in patients with a labyrinthine fistula. This change is associated with the labyrinthine fistula's depth and multiple fistulas-this is important during preoperative counseling of patients undergoing surgery.

TP53 signature predicts pathological complete response after neoadjuvant chemotherapy for breast cancer: Observational and confirmational study using prospective study cohorts.

The TP53 signature is considered a predictor of neoadjuvant chemotherapy (NAC) response and prognostic factor in breast cancer. The objective of this study was to confirm TP53 signature can predict pathological complete response (pCR) and prognosis in cohorts of breast cancer patients who received NAC in prospective studies. Development cohorts (retrospective [n = 37] and prospective [n = 216] cohorts) and validation cohorts (NAC administered prospective study cohorts [n = 407] and retrospective perioperative chemotherapy (PC)-naïve, hormone receptor (HrR)-positive cohort [PC-naïve_HrR+ cohort] [n = 322]) were used. TP53 signature diagnosis kit was developed using the development cohorts. TP53 signature predictability for pCR and the relationship between recurrence-free survival (RFS), overall survival (OS), and the TP53 signature were analyzed. The pCR rate of the mutant (mt) signature group was significantly higher than that of the wild-type (wt) signature group (odds ratio, 5.599; 95 % confidence interval = 1.876-16.705; P = 0.0008). The comparison of the RFS and OS between the HrR+ and HER2- subgroup of the NAC cohort and of the PC-naïve_HrR+ cohort indicated that the RFS and OS benefit of NAC was greater in the mt signature group than in the wt signature group. From post hoc analyses, the RFS and OS benefit from adding capecitabine to FEC+T as NAC might be observed only in the mt signature group. The TP53 signature can predict the pCR after NAC, and the RFS and OS benefit from NAC may be greater in the mt signature group than in the wt signature group.

Impact of Novel Agents on Patient Characteristics, Treatment Patterns, and Outcomes in Patients With Metastatic Castration-resistant Prostate Cancer.

BACKGROUND/AIM: The therapeutic landscape for metastatic castration-resistant prostate cancer (mCRPC) has changed dramatically with the introduction of several novel agents. However, limited data are available to determine whether the introduction of novel agents affected patient characteristics, treatment patterns, and outcomes compared with the period when these agents were not available. The objective of this study was to evaluate the impact of the introduction of novel mCRPC agents on patient characteristics, treatment patterns, and outcomes. PATIENTS AND METHODS: Two cohorts of Japanese patients diagnosed with mCRPC between 2009 and 2014 (Epoch 1) and 2015 and 2019 (Epoch 2) were retrospectively analyzed. RESULTS: A total of 125 treatment-naïve mCRPC patients, consisting of 42 patients in Epoch 1 and 83 patients in Epoch 2, were evaluated. We obtained the following results: (i) a dramatic shift in the first-line treatment from docetaxel to androgen receptor axis-targeted agents (ARATs), (ii) an age range expansion for first-line treatment, and (iii) an overall survival (OS) advantage in Eopch 2 compared to Epoch 1. Multivariate analysis in the overall population showed that Epoch 2 and low prostate-specific antigen (PSA) levels at the start of first-line treatment were independent prognostic factors for OS. CONCLUSION: In real-world mCRPC practice, the introduction of novel agents has improved the prognosis of mCRPC while allowing more patients to receive mCRPC treatment across a broad age range. In addition, low PSA levels at the start of first-line treatment were associated with improved OS, indicating the importance of starting mCRPC treatment while PSA levels are low.

Factors associated with non-completion of palliative radiotherapy for spinal metastasis in patients with terminal cancer: a retrospective study.

BACKGROUND: Predictors of non-completion of radiotherapy (RT) should be identified to determine the optimal RT dose. Therefore, this study aimed to explore factors associated with non-completion of palliative RT in patients with terminal cancer. METHODS: In this retrospective study, patients with terminal cancer who received RT (not including single-fraction RT) for relief of pain caused by spinal metastasis were categorized into complete and incomplete groups. Baseline characteristics, hematologic test data [e.g., total lymphocyte count (TLC)], performance status, palliative performance scale (PPS) score, psoas muscle index (PMI), Charlson comorbidity index, and age-adjusted Charlson comorbidity index of the patients were compared between the two groups. RESULTS: The complete group comprised 58 patients (median age: 68 years; female/male: 17/41; number of irradiation fractions: ≥2 to <10, 20 patients; 10, 34 patients; and >10, 4 patients), and the incomplete group comprised 9 patients (median age: 68 years; female/male: 3/6; number of irradiation fractions: ≥2 to <10, 2 patients; 10, 7 patients; and >10, 0 patient). The proportion of patient death within 1 week or 1 month was higher in the incomplete group than in the complete group. Compared with that in the incomplete group, TLC measured 1 week before RT (pre-TLC) and PMI recorded before RT were significantly higher in the complete group (P=0.013 and P=0.012, respectively). In multivariable analyses, pre-TLC was significantly associated with the incomplete group (P=0.048). Compared with the complete group, the incomplete group included several patients whose PPS scores rapidly decreased. CONCLUSIONS: Pre-TLC can predict non-completion of palliative RT in patients with terminal cancer.

The Japanese breast cancer society clinical practice guidelines for radiation treatment of breast cancer, 2022 edition.

The Breast Cancer Clinical Practice Guidelines, organized by the Japanese Breast Cancer Society (JBCS), were published in 2022. We present the English version of the Radiation Therapy (RT) section of the guidelines. The JBCS formed a task force to update the 2018 version of the JBCS Clinical Practice Guidelines. The Background Questions (BQs) contain the standard treatments for breast cancer in clinical practice, whereas the Clinical Questions (CQs) address daily clinical questions that remain controversial. Future Research Questions (FRQs) explore the subjects that are considered important issues, despite there being insufficient data for inclusion as CQs. The task force selected the 12 BQs, 8 CQs, and 6 FRQs for the RT section. For each CQ, systematic literature reviews and meta-analyses were conducted according to the Minds Manual for Guideline Development 2020, version 3.0. The recommendations, strength of recommendation, and strength of evidence for each CQ were determined based on systematic reviews and meta-analyses, and finalized by voting at the recommendation decision meeting.

The Japanese Breast Cancer Society Clinical Practice Guidelines for Breast Cancer, 2022 Edition: changes from the 2018 edition and general statements on breast cancer treatment.

The Japanese Breast Cancer Society Clinical Practice Guidelines for Breast Cancer, 2022 Edition was published in June 2022. The guidelines were prepared while conforming as much as possible to the "Minds Manual for Guideline Development 2020 ver. 3.0." edited by the Minds Manual Development Committee of the Japan Council for Quality Health Care in 2021. In addition, a survey of Japanese Breast Cancer Society members on the 2018 edition of the guidelines was conducted from February 19 to March 4, 2021. Based on the responses from over 600 members, original innovations were made to make the guidelines more user-friendly. The 2018 edition of the guidelines was developed to provide support tools for physicians and patients to utilize shared decision-making. The 2022 guidelines consist of two volumes: (1) an "Epidemiology and Diagnosis" section covering "Screening and Diagnosis", "Radiological diagnosis", and "Pathological diagnosis", and (2) a "Treatment" section covering "Surgical therapy", "Radiation therapy", and "Systemic therapy". We believe that this concise summary of the guidelines will be useful to physicians and researchers in Japan and overseas.

Augmented Reality-Assisted Transcanal Endoscopic Ear Surgery for Middle Ear Cholesteatoma.

Background: The indications for transcanal endoscopic ear surgery (TEES) for middle ear cholesteatoma have expanded for cases involving mastoid extension. However, TEES is not indicated for all cases with mastoid extension. In addition, predicting the extent of external auditory canal (EAC) removal needed for cholesteatoma resection is not always easy. The purpose of this study was to use augmented reality (AR) to project the lesion onto an intraoperative endoscopic image to predict EAC removal requirements and select an appropriate surgical approach. Methods: In this study, patients showing mastoid extension were operated on using a navigation system with an AR function (Stryker). Results: The results showed that some cases with lesions slightly extending into the antrum required extensive resection of the EAC, while cases with lesions extending throughout the antrum required smaller resection of the EAC, indicating TEES. Conclusions: By predicting the extent of the needed EAC removal, it is possible to determine whether TEES (a retrograde approach) or canal wall-up mastoidectomy, which preserves as much of the EAC as possible, should be performed. We believe that our findings will contribute to the success of middle ear surgeries and the implementation of robotic surgery in the future.

Trastuzumab deruxtecan for human epidermal growth factor receptor 2-low advanced or metastatic breast cancer: recommendations from the Japanese Breast Cancer Society Clinical Practice Guidelines.

The Japanese Breast Cancer Society Clinical Practice Guidelines are published as timely guidance on clinical issues in breast cancer treatment in Japan. In the recent edition of these guidelines, we addressed a new clinical question 34 (CQ 34, systemic treatment part) "Is trastuzumab deruxtecan recommended for patients with unresectable or metastatic HER2-low breast cancer?" and a new future research question 7 (FRQ 7, pathological diagnosis part) "How is HER2-low breast cancer diagnosed for the indication of trastuzumab deruxtecan?". These questions address use of trastuzumab deruxtecan in patients with unresectable or metastatic HER2-low breast cancer who have previously received chemotherapy for metastatic disease. The strengths of evidence and recommendation were determined through a quantitative and qualitative systematic review using multiple outcomes, including efficacy and safety. We conclude that trastuzumab deruxtecan is recommended for this patient population (strength of recommendation: 1; strength of evidence: moderate; CQ34) and that HER2-low expression for the indication of trastuzumab deruxtecan should be diagnosed using companion diagnostics based on appropriate criteria (FRQ7).

The Japanese Breast Cancer Society clinical practice guidelines for epidemiology and prevention of breast cancer, 2022 edition.

The Japanese Breast Cancer Society Clinical Practice Guidelines for Epidemiology and Prevention of Breast Cancer, 2022 Edition.

Prognostic Factors of Platinum-Refractory Advanced Urothelial Carcinoma Treated with Pembrolizumab.

INTRODUCTION: Immune checkpoint inhibitor (ICI) therapy has significantly improved the prognosis of some patients with advanced urothelial carcinoma (UC), but it does not provide high therapeutic efficacy in all patients. Therefore, identifying predictive biomarkers is crucial in determining which patients are candidates for ICI treatment. This study aimed to identify the predictors of ICI treatment response in patients with platinum-refractory advanced UC treated with pembrolizumab. METHODS: Patients with platinum-refractory advanced UC who had received pembrolizumab at two hospitals in Japan were included. Univariate and multivariate analyses were performed to identify biomarkers for progression-free survival (PFS) and overall survival (OS). RESULTS: Forty-one patients were evaluable for this analysis. Their median age was 75 years, and the vast majority of the patients were male (85.4%). The objective response rate was 29.3%, with a median overall survival (OS) of 17.8 months. On multivariate analysis, an Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥ 2 (HR = 6.33, p = 0.03) and a baseline neutrophil-to-lymphocyte ratio (NLR) > 3 (HR = 2.79, p = 0.04) were significantly associated with poor OS. Antibiotic exposure did not have a significant impact on either PFS or OS. CONCLUSIONS: ECOG-PS ≥ 2 and baseline NLR > 3 were independent risk factors for OS in patients with platinum-refractory advanced UC treated with pembrolizumab. Antibiotic exposure was not a predictor of ICI treatment response.