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Combination therapy with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors and hormonal therapy as the first-line and second-line treatments has already been shown to be effective in patients with hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) in clinical trials. On the other hand, in clinical practice, CDK4/6 inhibitors are used not only as first-/second-line but also as later-line hormonal therapies, or for patients receiving prior chemotherapy in metastatic setting. However, the efficacy and safety of combination therapy in these patients remain unclear. In this study, we evaluate the clinical efficacy and safety of combination therapy with abemaciclib and hormonal therapy for chemotherapy-treated patients with HR+ HER2- MBC.This multi-institutional prospective cohort study will involve a total of 300 chemotherapy-treated patients with HR+ HER2- MBC. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival, time to treatment failure, response rate, clinical benefit rate, and adverse events. The preplanned subpopulation analysis is the number of chemotherapy regimens for HR+ HER2- MBC (two or less vs. three or more), prior treatment history with CDK4/6 inhibitors other than abemaciclib (presence vs. absence) and menopausal status (pre vs. post). We also planned to determine PFS of the subpopulation treated with abemaciclib as maintenance therapy after chemotherapy.In this multi-institutional prospective cohort study, we evaluate the clinical efficacy and safety of combination therapy with abemaciclib and hormonal therapy for chemotherapy-treated patients with HR+ HER2- MBC. We also evaluate this combination therapy as maintenance therapy in patients who respond to early-line chemotherapy.

Background/Aim: We evaluated the efficacy and safety of tolvaptan for autosomal dominant polycystic kidney disease (ADPKD) in real-world practice. Patients and Methods: We retrospectively reviewed the cases of 27 patients who had been diagnosed with ADPKD between January 2014 and December 2022. Among them, 14 patients received tolvaptan (60 mg/day; morning: 45 mg, night: 15 mg) after being admitted for 2 days. In the outpatient clinic, blood and urine samples were taken monthly. Results: The mean age, pretreatment estimated glomerular filtration rate (eGFR), treatment duration, and total kidney volume were 60 years, 45.6 ml/min/1.73 m2, 2.8 years, and 2,390 ml, respectively. One month later, the patients’ renal dysfunction had worsened slightly, and their serum sodium concentrations had significantly increased. After one year, the mean reduction in the eGFR was –5.5 ml/min/1.73 m(2). Moreover, at 3 years the patients’ renal function was stable. No hepatic dysfunction or electrolyte abnormalities were noted, although discontinuation occurred in two cases. Tolvaptan treatment is considered to be safe. Conclusion: Tolvaptan was effective against ADPKD in a real-world setting. Moreover, the safety of tolvaptan was confirmed.

Background: Trastuzumab Deruxtecan (T-DXd) is a novel antibody-drug conjugate that targets human epidermal growth factor receptor 2 (HER2) with a DNA topoisomerase I inhibitor payload and has demonstrated antitumor activity in clinical trials. Based on the results of a global Phase II clinical trial (DESTINY-Breast01, NCT03248492), T-DXd was conditionally approved for the treatment of patients with HER2+ unresectable or metastatic breast cancer who had received ≥2 prior anti-HER2 based therapies (US, EU, UK, etc) or after prior chemotherapy (Japan). With regards to the safety profile, the incidence of cumulative toxicities such as peripheral neuropathy and edema was lower with T-DXd as compared to what has been observed with taxanes. However, chemotherapy-induced nausea and vomiting (CINV), fatigue, and neutrophil count decrease were observed as treatment emergent adverse events (TEAE). Interstitial lung disease (ILD)/pneumonitis was especially observed in 15.2% of patients treated with T-DXd, leading to death in 2.7% of patients. These adverse events need appropriate monitoring and management in daily clinical practice. We hypothesized that electronic patient-reported outcomes (ePROs) monitoring would allow early detection of adverse events due to T-DXd and thus improve patient safety and quality of life (QoL). Study design: This is an open-label, multicenter, randomized controlled study comparing ePRO monitoring with routine follow-up of patients with HER2+ advanced or metastatic breast cancer who receive T-DXd in routine clinical practice. Patients randomized to the ePRO group are monitored through weekly PRO-CTCAE assessment as well as daily temperature and SpO2 measurement using the ePRO application on the patient's mobile device. Changes in symptoms are monitored by the attending physician using an electronic chart. In addition, an e-mail alert is sent to the site medical staff if any symptoms exceed a predetermined threshold. The primary endpoint of the study is the change from baseline in the EORTC QLQ-C30 (Global QoL) score at 24 weeks. Secondary endpoints include time to deterioration of Global QoL, EORTC FA12 score change, overall survival, progression-free survival, and adherence to the ePRO monitoring as assessed by the proportion of patients completing the questionnaires. Analysis of primary endpoint will be done using mixed effects models for repeated measures (MMRM) and sample size will be estimated based on the Wald test for differences between groups in mean parameters at 24 weeks. To detect 10-points score difference between the groups with a standard deviation of 24, with a two-sided alpha level of 10%, and a power of 87%, 55 patients would be required in each group. Enrollment started in March 2021. Clinical trial identification: jRCTs031200387 Citation Format: Takafumi Sangai, Yuichiro Kikawa, Mitsuchika Hosoda, Yohei Hamanaka, Yuko Tanabe, Tatsuya Yoshida, Kaori Tane, Daisuke Takabatake, Tetsuhiko Taira, Kazuhiro Araki, Takayuki Iwamoto, Mamoru Takada, Kazutaka Narui, Takeshi Yamaguchi, Akimitsu Yamada, Tomoko Miura, Yukari Uemura, Tomohiko Aihara, Hirofumi Mukai, Naruto Taira. Randomized study comparing electronic patient reported outcomes (ePROs) monitoring with routine follow up during trastuzumab deruxtecan treatment in patients with inoperable or metastatic breast cancer (PRO-DUCE study) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-12-08.

BACKGROUND Androgen deprivation therapy (ADT) is one of the most effective treatments for advanced prostate cancer (PCa). However, it has been reported that the use of ADT is significantly associated with an increased risk of acute kidney injury (AKI) among patients with newly diagnosed non-metastatic PCa. We investigated changes in renal function that occurred in Japanese patients with PCa after ADT was discontinued. PATIENTS AND METHODS Among 121 patients who underwent prostate biopsies, were pathologically diagnosed with PCa, and received ADT for ≥6 months at our Institution between 2009 and 2014, 60 patients who underwent radiotherapy for stage B or C PCa were eligible for inclusion in this retrospective study. Renal function was assessed using the estimated glomerular filtration rate (eGFR) before treatment and at 1, 3, 6, 9, and 12 months after the initiation of ADT and the rate of change in the eGFR (ΔeGFR) during ADT and after the discontinuation of ADT was investigated. We divided patients into two groups: Group 1 received ADT for 6 months, and group 2 received ADT for 12 months. Age; ΔeGFR; prostate-specific antigen, testosterone and hemoglobin levels; clinical stage; Gleason score; comorbidities; body mass index; heart rate; and the cardiothoracic ratio were analyzed. RESULTS A total of 60 patients (group 1: n=23, group 2: n=37) were analyzed. The Gleason score of group 2 was higher than that of group 1 (p=0.0011). Regarding clinical stage, group 1 had more patients with stage B disease, and group 2 had more with stage C (p

ObjectivesWhole SARS-CoV-2 genome sequencing from COVID-19 patients is useful for infection control and regional trends evaluation. We report a lineage data collected from hospitals in the Kanto region of Japan.MethodsWe performed whole genome sequencing in specimens of 198 COVID-19 patients at 13 collaborating hospitals in the Kanto region. Phylogenetic analysis and fingerprinting of the nucleotide substitutions underwent to differentiate and classify the viral lineages.ResultsMore than 90% of the strains belonged to Clade 20B and two lineages (B.1.1.284 and B.1.1.214) have been detected predominantly in the Kanto region. However, one sample from a COVID-19 patient in November 2020, belonged to the B.1.346 lineage of Clade 20C, which has been prevalent in western United States. The patient had no history of overseas travel and no contact with anyone who had travelled abroad, suggesting that this strain appeared likely to have been imported from western United States, across the strict quarantine barrier.ConclusionB.1.1.284 and B.1.1.214 have been identified predominantly in the Kanto region and B.1.346 of clade 20C in one patient was probably imported from western United States. These results illustrate that a decentralized network of hospitals can be significantly advantageous for monitoring regional molecular epidemiologic trends.Highlights· Whole SARS-CoV-2 genome sequencing is useful for infection control· B.1.1.284 and B.1.1.214 have been identified predominantly in the Kanto region· B.1.346 of Clade 20C was detected in one COVID-19 patient in November· Molecular genomic data sharing provides benefits to public health against COVID-19

Introduction 123I-metaiodobenzylguanidine scanning has high sensitivity and specificity for the diagnosis of tumors derived from sympathetic nerves or the adrenal medulla. We report the rare case of a 123I-metaiodobenzylguanidine false-positive renal cell carcinoma. Case presentation The patient was referred to our hospital with an incidental left renal mass during evaluation for hypertension. An ovarian tumor and prominent ascites were also observed. Serum and urine catecholamine levels were high to suspect a catecholamine-producing tumor of the kidney. 123I-metaiodobenzylguanidine scintigraphy showed increased 123I-metaiodobenzylguanidine intake in the tumor. Laparoscopic radical left nephrectomy was performed. The pathologic diagnosis was an oncocytic variant of chromophobe renal cell carcinoma. No pheochromocytoma features were found. Conclusion We report the first case of a 123I-metaiodobenzylguanidine false-positive renal cell carcinoma. This case was diagnosed with primary aldosteronism and Meigs' syndrome, which made the clinical course more complicated.

Background The HORSE-BC study previously demonstrated that second-line endocrine therapy (ET) for patients with acquired endocrine-resistant metastatic breast cancer (MBC) still provided a clinically meaningful benefit. Herein, we investigated the health-related quality of life (HR-QOL) in the HORSE-BC study. Methods Patients with acquired endocrine-resistant MBC who were scheduled for second-line ET were recruited. The HR-QOL was assessed at baseline, and 1 and 3 months after second-line ET initiation. To investigate the minimally important difference (MID) in the Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES), we evaluated the means and standard deviations for the distribution-based method, and differences in the change in HR-QOL for the anchor-based method. We also investigated the association between FACT-ES total scores and clinical benefit. Results Overall, 56 patients were enrolled. Of these, 47 were analyzed. When defined as 1/3 standard deviation estimates based on the distribution method, the calculated MID was 5.9. The MIDs of the FACT-ES total scores based on the anchor method were 7.7 for decline and 4.1 for improvement. The MID decline proportions were 6.1% and 14.7% lower in patients who experienced clinical benefits than in those who did not at 1 and 3 months, respectively. The ratios of MID improvement in patients who experienced clinical benefits were 18.3% and 3.2% higher, respectively; the mean change in the FACT-ES total score from baseline improved in patients who experienced clinical benefits. Conclusions Maintaining the HR-QOL as determined by FACT-ES may be associated with clinical benefits in patients with acquired endocrine-resistant MBC treated with ET.

A 34-year-old man visited our hospital complaining of a small painless left scrotal mass. His serum alpha-fetoprotein and human chorionic gonadotropin-beta levels were normal. Ultrasonography revealed a solitary 14 mm mass. Magnetic resonance imaging revealed a mass with high intensity on T2-weighted imaging. Computed tomography revealed a heterogeneous tumor in the left scrotum. Left high orchiectomy was performed. The histopathological diagnosis was a teratoma without germ cell neoplasia in situ (GCNIS). Fluorescence in situ hybridization analysis showed no appearance of i(12p). The patient was clinically diagnosed as having a prepubertal-type testicular teratoma. Adult teratomas contain GCNIS and are aggressively treated as malignant germ cell tumors. However, a prepubertal-type teratoma is benign and does not relapse. It is essential to validate the appearance of i(12p) to differentiate prepubertal and postpubertal-type teratoma.

Background/Aim: We investigated the changes in and characteristics of renal function in Japanese patients with high-risk prostate cancer (PCa) who underwent radiotherapy and long-term androgen deprivation therapy (ADT), including those seen after the ADT was discontinued. Patients and Methods: Among 60 patients who were pathologically diagnosed with PCa and received ADT for 24 months and radiotherapy, 36 patients who underwent treatment for stage B or C PCa were eligible. We assessed renal function using the estimated glomerular filtration rate (eGFR) and investigated the rate of change in the eGFR (ΔeGFR) during and after ADT. Univariate and multivariate logistic analyses were carried out to identify clinical factors that were significantly associated with renal dysfunction at 36 months. Results: The incidence of renal dysfunction at 36 months was 75% (27/36). Multivariate analysis showed that the presence/absence of HF was an independent predictor of renal dysfunction at 36 months. Conclusion: Renal function tended to recover after ADT was received for 24 months and subsequently discontinued. The presence/absence of HF represents new and meaningful information for patients receiving ADT, and high-risk PCa patients prior to ADT.

Background/Aim: There are few reports about the administration of nivolumab plus ipilimumab to hemodialysis patients and their efficacy and safety have not been established yet. Case Report: A 74-year-old male, who was receiving hemodialysis, was presented with metastatic renal cell carcinoma (mRCC). Two years later, more metastases were found, hence, immunotherapy involving nivolumab plus ipilimumab was initiated. After two doses of immunotherapy, interstitial pneumonia was observed. Thus, steroid pulse therapy was administered immediately. Subsequently, computed tomography (CT) findings and symptoms improved markedly. One month later, a CT scan showed a nodular shadow and an air cavity. A fungal infection was strongly suspected, so an antifungal drug was administered. Conclusion: Combination immunotherapy with nivolumab plus ipilimumab was demonstrated to be effective in a hemodialysis patient with mRCC.

Background/aim This study aimed to access the effectiveness of serum neutrophil-to-lymphocyte ratio (NLR) in patients undergoing prostate needle biopsy with a prostate specific antigen (PSA) between 4.0 and 10.0 ng/ml. Patients and methods A total of 633 cases were eligible. We evaluated several factors including age, PSA, PSA-density (PSAD), platelet-to-lymphocyte ratio (PLR) and NLR in the presence or absence of prostate cancer (PCa), retrospectively. We evaluated statistically the associations between each factor and pathological findings or Gleason score. Results A total of 201 were evaluated in this study. Regarding the presence or absence of prostate cancer, there were statistically significant differences in age, PSA levels, PSAD, the PLR and NLR. The mean NLR value of the patients with PCa was significantly lower compared to the entire cohort. Multivariate analysis showed that age, PSAD, and NLR were independent risk factors predicting PCa. Conclusion For patients having a PSA between 4.0 and 10.0 ng/ml, NLR was a predicting factor of PCa prior to prostate needle biopsy and an effective biomarker and useful tool for avoiding unnecessary biopsies.

Aspergillus fumigatus is the commonest cause of pulmonary aspergillosis; however, a recently developed molecular genetic technique identified A. lentulus as a sibling species. Most of the isolates were found in solid organ recipients, often associated with a fatal outcome. Moreover, there is concern that A. lentulus has low susceptibility to multiple antifungal agents. Herein, we report an adult immunocompromised patient with proven invasive pulmonary aspergillosis (IPA) caused by A. lentulus, which was identified through molecular genetic analysis. The patient was diagnosed with IPA by bronchoscopy 3 weeks after initiating systemic corticosteroid therapy for anti-neutrophil cytoplasmic antibody-associated vasculitis. The clinical course of IPA due to A. lentulus showed improvement after treatment with the antifungal agent voriconazole. In summary, we report an adult immunocompromised patient without a history of transplantation who was diagnosed with IPA due to A. lentulus successfully treated with voriconazole, and we also report the findings of a literature review on IPA caused by A. lentulus.

Background: Docetaxel + Trastuzumab (H) + Pertuzumab (P) provided progression-free survival (PFS) and overall survival (OS) benefits in HER2-positive advanced or metastatic breast cancer (AMBC) in the CLEOPATRA study as a first-line therapy. However, long-term administration of docetaxel at a dose of 75 mg/m2 every 3 weeks in AMBC patients (pts) is difficult due to the toxicities. Eribulin mesylate (E) is a well-tolerated microtubule inhibitor, and we have reported the efficacy and safety of EHP regimen as first- and second-line therapy for AMBC in a multicenter, phase II study (JBCRG-M03/UMIN000012232). In this M06 study, we address the clinical question as to which is the better chemotherapy partner for HP as first line regimen, in terms of efficacy, toxicity and QOL. Methods: JBCRG-M06 is a multicenter open-label randomized phase III study for HER2-positive AMBC pts who have received no prior chemotherapy except for the HER2- Antibody-Drug Conjugate (ADC). Pts will be randomized 1:1 to E (1.4mg/m2 on day 1 and 8) + H (8 mg/kg loading dose followed by 6 mg/kg) +P (840 mg loading dose followed by 420 mg) q3wks or standard taxanes (docetaxel 75mg/m2 on day1 or paclitaxel 80mg/m2 on day 1, 8 and 15) + HP q3wks. Stratification factors for randomization are; presence of visceral metastases, number of prior taxanes on perioperative adjuvant treatment, and treatment with prior anti-HER2-ADC. Primary endpoint is PFS and secondary endpoints include overall response rate, duration of response, OS, patient-reported outcomes (PRO) relating to QOL and peripheral neuropathy, new-metastases free survival, and safety. Translational research to search for biomarker for individual precision therapy will be performed. Main eligibility criteria are as follows: pts with HER2-positive AMBC, female aged 20-70 years old, ECOG PS of 0-1, LVEF ≥ 50% at baseline and adequate organ function. Pts who had progressive MBC within 6 months after the end of primary adjuvant systemic chemotherapy are excluded. The sample size was calculated by type1 error (2-sided) of 0.05 and 80% power to estimate the noninferiority margin 1.33 with an expected median PFS of 14.2 months. The target number of pts is 480 recruited over the duration of 3-years. The first patient in was achieved on August 2017. (ClinicalTrials.gov Identifier:NCT03264547). Citation Format: Masuda N, Yamashita T, Saji S, Araki K, Ito Y, Takano T, Takahashi M, Tsurutani J, Koizumi K, Kitada M, Kojima Y, Sagara Y, Tada H, Iwasa T, Kadoya T, Iwatani T, Hasegawa H, Morita S, Ohno S. A phase III trial to compare eribulin mesylate + trastuzumab (H) + pertuzumab (P) with paclitaxel or docetaxel + HP for HER2-positive advanced or metastatic breast cancer (JBCRG-M06/ EMERALD) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT2-07-05.

Background:It is unclear how to define responsiveness to endocrine therapy (ET) during the clinical course of advanced breast cancer (ABC), especially in evaluation of the effect of sequential ET. Objective:The goal of the study was to evaluate the efficacy of second line treatment of physician's choice (2nd-line TPC) for estrogen receptor-positive (ER+) and HER2-negative postmenopausal ABC with very low or low sensitivity to initial ET. Methods:A multicenter prospective observational cohort study was performed for 2nd-line TPCs. ABC with low sensitivity to initial ET was defined as recurrence within 5 years (yrs) during adjuvant ET or progression within 9 months (mo.) of initial ET. Similarly, ABC with very low sensitivity to initial ET was defined as recurrence within 2 yrs during adjuvant ET or progression within 3 mo. of initial ET. The expected clinical benefit rate (CBR: defined as patients who achieved CR, PR or SD for 24 weeks) was 50%. The null hypothesis of a CBR of 30% was tested with a one-sided α of 5%. 90% confidence intervals (CIs) were calculated for hypothesis tests. Results: A total of 56 patients (pts) were enrolled, but 7 were ineligible and one discontinued before starting the protocol treatment. The median age was 66 yrs (range: 41-88) and the median BMI was 23.4 kg/m2 (16.4-31.9). All pts were ER+ and 80% were PgR+. Most of pts had a baseline PS of 0 or 1, 90% had invasive ductal carcinoma, and 10% had invasive lobular carcinoma. Postoperative recurrence was detected in 84% and these pts had a median duration of adjuvant ET of 30.5 mo. (5.3-58.9). De novo stage IV ABC was present in 16%, with a median duration of first-line ET of 5 mo. (2.3-10.8). Adjuvant chemotherapy including anthracycline- and/or a taxane-containing regimen was administered in 58% (29/49). As adjuvant ET before initial recurrence, 34 pts received non-steroidal aromatase inhibitors (AIs) (88.0%), 1 received a steroidal AI (2.3%), and 3 received a selective estrogen receptor modulator (SERM). As first line ET in de novo stage IV, 7 pts (14%) were treated with AIs or a SERM (1 case). 2nd-line TPCs were also used, with 40 pts receiving fulvestrant (82%), 5 receiving SERMs (10%), 3 receiving a mTOR inhibitor plus a steroidal AI (6%), and one patient receiving an AI alone. The overall CBR was 44.9% (90% CI: 34.6-57.6, p=0.009), and CBR was similar across following subgroups (PgR+: n=39, 51.3%, 90% CI: 39.6-65.2, p=0.0016; very low sensitivity group: n=17, 58.8%, 90% CI: 42.0-78.8, p=0.003; non-visceral metastases: n=25, 40%, 90% CI; 34.1-65.9, p=0.0175). However, there were not statistically significant CBR in PgR- (n=10, 20.0%, 90% CI; 8.73-50.7, p=0.617), fulvestrant subgroup (n=40, 40.0 %, 90% CI; 29.2-54.2, p=0.063), low sensitive group (n=32, 37.5%, 90% CI; 26.0-53.6, p=0.1326), and visceral metastases (n=24, 48%, 90%CI; 28.2-60.3 p=0.072). The median PFS was 7.1 mo. (95% CI: 5.6-10.6). Conclusion:This study shows that 2nd line ETs was effective and might be a valid option in the sequence of treatments for postmenopausal women with ABC with low sensitivity to initial ET. It was suggested that PgR and visceral metastasis were significant predictive factors for CBR. Citation Format: Araki K, Fujisawa T, Sakamaki K, Kikawa Y, Iwamoto T, Sangai T, Shien T, Takao S, Nishimura R, Takahashi M, Aihara T, Mukai H, Taira N. Sequential second line endocrine therapy is still an effective strategy for postmenopausal ER+ and HER2- advanced breast cancer with low sensitivity to initial endocrine therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-13-09.

Although peripheral blood-based parameters (PBBPs) are reported as prognostic indicators in patients with breast cancers, their utility has not been studied in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC). Tumor-infiltrating lymphocytes (TILs) might be a predictive factor in patients with HER2-positive ABC treated with pertuzumab and trastuzumab (PT) plus docetaxel. We aimed to evaluate whether PBBPs could have predictive value in HER2-positive ABC treated with pertuzumab and trastuzumab (PT) combined with eribulin (ERI) or nab-paclitaxel (Nab-PTX). Data from 51 patients included in two single-arm, phase II trials were included in this retrospective-prospective study; the ERI + PT (N = 30) and Nab-PTX + PT (N = 21) combinations were registered under clinical trials number UMIN000012375 and UMIN000006838, respectively. We assessed PBBPs using prospectively collected data and investigated the association with progression-free survival (PFS); we evaluated absolute lymphocyte count (ALC), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR). The cutoff values for ALC, NLR, and PLR were set at 1000 or 1500 cells/μL, 2, and 250, respectively. PFS was significantly improved in patients with ALC ≥1500/μL compared to those with ALC 1000–

Although eribulin and nab-paclitaxel are chemotherapy agents widely used for locally advanced or metastatic breast cancer (MBC), their predictive factors remain unknown. Because the absolute neutrophil-to-lymphocyte ratio (NLR) is a significant prognostic factor for early-stage breast cancer, we investigated its usefulness in terms of the eribulin or nab-paclitaxel treatment efficacy for MBC.A total of 85 patients with MBC treated with eribulin (n = 59) or nab-paclitaxel (n = 26) were recruited. NLR values were collected at baseline, after 1 cycle, after 2 cycles, and at the end of treatment. The NLR cutoff value was set at 3.The progression-free survival (PFS) of patients with an NLR 3 at baseline (median, 242 days; n = 24) was significantly better than that of patients with an NLR of ≥ 3 (median, 98 days; n = 35; hazard ratio, 0.37, 95% confidence interval, 0.18-0.71; P = .0032). Similarly, the overall survival was marginally significantly better in patients with an NLR 3 who were treated with eribulin (P = .058). However, the NLR was not significantly associated with PFS or overall survival for patients treated with nab-paclitaxel. No significant association was found between the NLR during treatment and PFS in the eribulin group. The significance of the NLR for the efficacy of eribulin was consistent, irrespective of estrogen receptor status, previous anthracycline or endocrine use, and the number of previous chemotherapy regimens.A low NLR at baseline was significantly associated with improved PFS in patients treated with eribulin but not in those treated with nab-paclitaxel. Therefore, the baseline NLR might be clinically useful for selecting patients who would benefit from eribulin.

Background/Aim: Recently, it was reported that the use of androgen deprivation therapy (ADT) is significantly associated with an increased risk of acute kidney injury (AKI) in patients with newly diagnosed non-metastatic prostate cancer. This study aimed to investigate the incidence of early renal dysfunction in Japanese prostate cancer patients receiving ADT and the factors associated with it. Patients and Methods: A total of 135 patients who had been pathologically diagnosed with prostate cancer and had received ADT for at least 6 months were eligible for study inclusion. The estimated glomerular filtration rate (eGFR) before treatment, and at 1, 3, and 6 months of ADT were evaluated retrospectively. We assessed renal function using eGFR and investigated the rate of change in the eGFR (ΔeGFR) during ADT. Univariate and multivariate logistic analyses were carried out to identify clinical factors that were significantly associated with renal dysfunction after 6 months ADT. Results: A total of 110 cases were evaluated in this study. The incidence of renal dysfunction after 6 months ADT was 63% (69/110). The mean ΔeGFR after 1, 3, and 6 months of ADT were –0.6%, –3.1% and –1.7%, respectively (p

Objectives. To determine whether an alkaline phosphatase (ALP) flare after androgen deprivation therapy (ADT) is associated with the treatment response in castration-resistant prostate cancer (CRPC) and predicts the prognosis of metastatic prostate cancer (PCa) patients. Methods. One hundred and nineteen patients diagnosed with metastatic PCa between 2008 and 2017 were retrospectively studied. The ALP flare ratio was calculated as the ratio of ALP levels 1 month after beginning ADT to ALP levels at diagnosis. The association of the ALP flare ratio with the prostate-specific antigen (PSA) response to CRPC treatment (second-generation androgen receptor targeted therapy (ART) or docetaxel), time to CRPC, and overall survival (OS) were investigated. Results. The time to CRPC and OS was significantly longer in patients with an ALP flare ratio less than 1.33 compared to a ratio more than 1.33. No difference in PSA response was seen regarding the ALP flare ratio in both ART and docetaxel treatment. Second-generation ART-treated patients with a low ALP flare ratio showed longer OS than those with a higher ALP flare ratio ( p = 0.0367 ). However, no difference was seen between a high and low ALP flare ratio ( p = 0.8054 ) in docetaxel-treated patients. The ALP flare ratio was the most significant prognostic factor for OS ( p < 0.0001 ). Conclusions. A higher ALP flare ratio after first-line ADT was a significant prognostic factor in metastatic PCa, especially in patients treated with second-generation ART for CRPC. Chemotherapy for patients with a higher ALP flare ratio 1 month after induction of ADT may be a clinically relevant decision.

Purpose Second-line endocrine therapy (ET) for estrogen receptor (ER)-positive and human epidermal growth factor 2 (HER2)-negative metastatic breast cancer (MBC) is offered based on the response to first-line ET. However, no clinical trials have evaluated the efficacy and safety of secondary ETs in patients with poor responses to initial ET. This study evaluated the efficacy of second-line ET in ER-positive and HER2-negative postmenopausal MBC patients with low or very low sensitivity to initial ET. Methods This multicenter prospective observational cohort study evaluated the response of 49 patients to second-line ETs in postmenopausal MBC patients with low or very low sensitivity to initial ET. The primary endpoint was the clinical benefit rate (CBR) for 24 weeks. Results Of the 49 patients assessed, 40 (82%) received fulvestrant in the second line, 5 (10%) received selective estrogen receptor modulators, 3 (6%) received aromatase inhibitors (AIs) alone, and 1 received everolimus with a steroidal AI. The overall CBR was 44.9% [90% confidence interval (CI): 34.6–57.6, p = 0.009]; CBR demonstrated similar significance across the progesterone receptor-positive (n = 39, 51.3%, 90% CI: 39.6–65.2, p = 0.002), very low sensitivity (n = 17, 58.8%, 90% CI: 42.0–78.8, p = 0.003), and non-visceral metastases (n = 25, 48.0%, 90% CI: 34.1–65.9, p = 0.018) groups. The median progression-free survival was 7.1 months (95% CI: 5.6–10.6). Conclusion Second-line ET might be a viable treatment option for postmenopausal patients with MBC with low and very low sensitivity to initial ET. Future studies based on larger and independent cohorts are needed to validate these findings.

Background: Tumor-infiltrating lymphocytes might be a one of predictive outcome of human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC) patients (pts) who treated with trastuzumab and pertuzumab (TP) plus docetaxel. Although peripheral blood-based parameter (PBBP) is reported as a prognostic indicator of patients with early breast cancers, utility of PBBP has not been studied in HER2-positive ABC. Objective:The aim of our study was to determine whether PBBP is significant for predictive efficacy in HER2-positive ABC treated with TP combined with eribulin (ERI) or nab-paclitaxel (Nab-PTX). Methods: The 51 patients' data from two single arm phase II trials was included in this retrospective-prospective study; ERI + TP (n=30) or Nab-PTX + TP (n=21) registered with UMIN000012375 or UMIN000006838, respectively. We assessed the PBBP in prospectively collected data and investigated their association with progression-free survival (PFS). In consideration of PBBP, we evaluated absolute lymphocyte count (ALC), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR). The cutoff values of ALC, NLR, and PLR were set at 1000 cells/μL, 2, and 250, respectively. Results:Median age at baseline was 58 years (range: 31-77). Median number of previous chemotherapy was 3 (range: 1-10). Pts had multiple metastases, 53% with LNs, 35% with bone, 25% with lung, 20% with liver, and 6% with brain. The objective response rate (CR+PR) and clinical benefit rate (CR+PR+ more than 6 month SD) were 37% (n=19) and 59% (n=30), respectively. The median PFS of all pts was 301 days (range: 21-1281). The PFS of pts with ALC-High was significantly better than those of ALC-low (hazard ratio (HR): 2.74, 95% confidence interval (CI): 1.28 to 5.86; p= .0097). Furthermore, improved PFS was obtained in pts with ALC greater than 1500 cells/μL compared with less than 1000 cells/uL (HR: 4.05, 95% CI: 1.60 to 11.6; p= .0029). Significant associations seem to exist irrespective of number of previous chemotherapy. Since we combined different studies for evaluating PBBP, ERI and Nab-PTX were calculated separately. Marginally significant associations between ALC and PFS were obtained both in ERI (HR: 2.18, 95% CI: 0.87 to 5.60; p=.0973) and Nab-PTX (HR: 3.26, 95% CI: 0.80 to 12.4; p=.0939). The PFS of NLR-low pts was significantly better than those of NLR-high (HR: 2.29, 95% CI: 1.01 to 5.90; p= .0477), but this statistical difference was inferior to those of ALC. There was no significant association between PLR and PFS. Conclusions: Pre-treatment ALC-High was significantly correlated with favorable PFS of pts treated with TP irrespective of combination chemotherapy in HER2-positve ABC. Prolonged PFS of TP combination therapy might be obtained mediating through host systemic onco-immunity. These data obtained here suggest that a usefulness of ALC for selecting pts who might have clinical benefit from TP combination therapy for heavily treated HER2-positve ABC. Citation Format: Araki K, Ito Y, Fukada I, Kobayashi K, Ohno S, Miyagawa Y, Imamura M, Kira A, Takatsuka Y, Egawa C, Suwa H, Miyoshi Y. Predictive impact of absolute lymphocyte counts for progression-free survival in HER2-positive advanced breast cancer treated with pertuzumab and trastuzumab plus eribulin or nab-paclitaxel [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-09-31.

Purpose To evaluate the association between tumor shrinkage patterns shown with magnetic resonance (MR) imaging during neoadjuvant chemotherapy (NAC) and prognosis in patients with low-grade luminal breast cancer. Materials and Methods This retrospective study was approved by the institutional review board and informed consent was obtained from all subjects. The low-grade luminal breast cancer was defined as hormone receptor-positive and human epidermal growth factor receptor 2-negative with nuclear grades 1 or 2. The patterns of tumor shrinkage as revealed at MR imaging were categorized into two types: concentric shrinkage (CS) and non-CS. Among 854 patients who had received NAC in a single institution from January 2000 to December 2009, 183 patients with low-grade luminal breast cancer were retrospectively evaluated for the development set. Another data set from 292 patients who had received NAC in the same institution between January 2010 and December 2012 was used for the validation set. Among these 292 patients, 121 patients with low-grade luminal breast cancer were retrospectively evaluated. Results In the development set, the median observation period was 67.9 months. Recurrence was observed in 31 patients, and 16 deaths were related to breast cancer. There were statistically significant differences in both the disease-free survival (DFS) and overall survival (OS) rates between patterns of tumor shrinkage (P < .001 and P < .001, respectively). Multivariate analysis demonstrated that the CS pattern had the only significant independent association with DFS (P = .001) and OS (P = .009) rate. In the validation set, the median follow-up period was 56.9 months. Recurrence was observed in 20 patients (16.5%) and eight (6.6%) deaths were related to breast cancer. DFS rate was significantly longer in patients with the CS pattern (72.8 months; 95% confidence interval [CI]: 69.9, 75.6 months) than in those with the non-CS pattern (56.0 months; 95% CI: 49.1, 62.9 months; P ≤ .001). The CS pattern was associated with an excellent prognosis (median OS, 80.6 months; 95% CI: 79.3, 81.8 months vs 65.0 months; 95% CI: 60.1, 69.8 months; P = .004). Multivariate analysis demonstrated that the CS pattern had the only significant independent association with DFS (P = .007) and OS (P = .037) rates. Conclusion The CS pattern as revealed at MR imaging during NAC had the only significant independent association with prognosis in patients with low-grade luminal breast cancer. © RSNA, 2017.

Background The efficacy and safety of continuing multiple anti-HER2 therapies in advanced breast cancer (ABC) patients remains unclear. This study investigated eribulin in combination with pertuzumab and trastuzumab for both taxane- and trastuzumab-pretreated HER2-positive ABC patients. Methods In a single-institute, single-arm, open-label, phase II trial, HER2-positive ABC patients who had previously received taxanes and trastuzumab were treated with eribulin in combination with pertuzumab and trastuzumab. The pharmacokinetics of eribulin in this combination were assessed in 6 patients. Tumor assessments were conducted every 6 weeks for the first 6 cycles and every 12 weeks thereafter. The primary endpoint was objective response rate (ORR). Results A total of 30 patients (median age, 58 years; range, 31–76) were enrolled, with a median number of previous chemotherapy regimens of 3.5 (range: 1–9) in the metastatic setting. Pharmacokinetic parameters of eribulin in this combination were similar to previous reports of eribulin monotherapy. ORR was 34.8% (95% CI: 16.4–57.3, n = 23), and median progression-free survival was 42.6 weeks (95% CI: 20.3–51.9, n = 30). Clinical benefit rate was 60.9% (95% CI: 16.4–57.3). The most common grade 3/4 adverse event was neutropenia in 20 patients (66.7%). A dose reduction of eribulin was required in 27 patients due to adverse events, particularly grade 3 neutropenia. Conclusions Eribulin in combination with pertuzumab and trastuzumab was well tolerated in heavily pretreated patients. Eribulin may be a viable treatment option when used in combination with pertuzumab and trastuzumab for HER2-positive ABC patients (UMIN Clinical Trial Registry identification number, UMIN000012375).

Background Trastuzumab (Tmab), pertuzumab (Pmab), and taxane has been a standard first-line treatment for recurrent or metastatic human epidermal growth factor (HER2)-positive breast cancer (HER2+ mBC) but has some safety issues due to taxane-induced toxicities. This has led to ongoing efforts to seek less toxic alternatives to taxanes that are equally effective when used in combination with Tmab plus Pmab. This study aims to show the non-inferiority of eribulin, a non-taxane microtubule inhibitor, against taxane, as a partner for dual HER2 blockade. Methods/design This multicenter, randomized, open-label, parallel-group, phase III study will involve a total of 480 Japanese women with HER2+ mBC who meet the following requirements: (1) age 20–70 years; (2) no prior cytotoxic chemotherapy (excluding trastuzumab-emtansine) for mBC; (3) ≥ 6 months after prior neoadjuvant or adjuvant cytotoxic chemotherapy; (4) presence of any radiologically evaluable lesion; (5) left ventricular ejection fraction ≥ 50%; (6) Eastern Cooperative Oncology Group performance status score of 0 or 1; (7) adequate organ function; and (8) life expectancy of at least 6 months. They will be randomized 1:1 to receive eribulin (1.4 mg/m2 on days 1 and 8) or taxane (docetaxel 75 mg/m2 on day 1 or paclitaxel 80 mg/m2 on days 1, 8, and 15) in combination with Tmab (8 mg/kg then 6 mg/kg) plus Pmab (840 mg then 420 mg) on day 1 of each 21-day cycle. The treatment will be continued until disease progression or unmanageable toxicity. The primary endpoint is progression-free survival as per investigator according to RECIST v1.1 criteria. Key secondary endpoints include objective response rate, overall survival, quality of life and safety. Non-inferiority will be tested with two margins of 1.33 and 1.25 in a stepwise manner. If non-inferiority is shown with a margin of 1.25, superiority will then be tested. Discussion If this study shows the non-inferiority, or even superiority, of Tmab, Pmab, and eribulin against the existing taxane-containing regimen, this new regimen may become a standard first- or second-line treatment option for HER2+ mBC in Japan. Trial registration ClinicalTrials.gov, ID: NCT03264547. Registered on 28 June 2017.

The combination chemotherapy regimen of eribulin (ERI) and trastuzumab (TRA)—the ERI-TRA regimen—has been shown to be highly tolerable for patients with recurrent or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, no sufficient clinical evidence is available for the long-term safety profile of the regimen. We report on three patients in the Phase I combination study of the regimen, for whom the regimen could be conducted over the long term. Patient #1 was a 68-year-old woman and underwent the regimen until cycle 23. Patient #2 was a 61-year-old woman and underwent the regimen until cycle 27. Patient #3 was a 59-year-old woman and underwent the regimen until cycle 22. All these patients had undergone TRA-based combination therapy before the onset of the regimen. Any new categories of adverse events did not occur in association with the long-term combination chemotherapy. Neutropenia experienced by these patients was reversible and easily manageable by dose adjustment (interruption/delay and reduction). Neither increase in the risk of cardiomyopathy nor the worsening of peripheral neuropathy greater than grade 1 was found. The present regimen was suggested to be a novel chemotherapeutic option for patients with HER2-positive recurrent or metastatic breast cancer. The fact that the long-term ERI-TRA regimen was successfully conducted for these patients can be supplementary clinical information that is beneficial for clinical oncologists.

Background Multiple anti-HER2 therapies have improved the outcome for patients with HER2-positive breast cancer. However, optimal management has yet to be established for lapatinib (LAP)- and trastuzumab (Tmab)-resistant disease progression. Data from our institution were reviewed to contribute to the search for best practices. Patients and Methods Between June 2009 and March 2013, 74 HER2-positive advanced breast cancer (ABC) patients were treated with LAP with capecitabine (LAPCAP). Patients re-treated with Tmab-based chemotherapies were identified, with a focus on baseline characteristics, chemotherapies, and efficacy. The study focused on the clinical outcomes of 50 patients re-treated with Tmab after LAPCAP-resistant disease progression (LAPCAP-PD), with an assessment of tumor response and clinical benefit (CB). Progression-free survival (PFS) was used as a predictive surrogate marker for the efficacy of Tmab rechallenge. Results All patients were pretreated with Tmab- and LAP-based chemotherapies. At a median follow-up of 7.9 months, PFS was 4.6 months, and overall survival was 33.7 months after LAPCAP-PD. Rechallenges with Tmab-based chemotherapies included gemcitabine (GEM) in 23 patients, vinorelbine in 14, taxanes in 5, endocrine treatments in 2, and others. The CB rate was 32%, including complete response for 1, partial response for 3, and > 6 months of stable disease for 12. Although the median PFS was longer for patients treated with microtubule inhibitors (MTIs) than with GEM, various chemotherapies had different efficacy regardless of whether or not previous LAPCAP had CBs. Conclusion Tmab rechallenge combined with not only MTIs but also an antimetabolite agent is effective against some LAPCAP-PD HER2-positive ABC.

We aimed to confirm the efficacy of fulvestrant in Japanese postmenopausal advanced/recurrent breast cancer (ABC) patients, and investigate factors contributing to time-to-treatment failure (TTF) prolongation.This retrospective study included 194 ABC patients who received fulvestrant (500 mg) from January 2012 to December 2014.TTF (efficacy measure), overall survival (OS), factors prolonging TTF and adverse events were evaluated.The median age was 65 (42 - 90) years. Overall, TTF was 5.48 months. In patients without prior chemotherapy (n = 59), OS was significantly longer (p = 0.0131) than in patients with prior chemotherapy (n = 135). There was no strong correlation between TTF with fulvestrant and other endocrine therapies, total duration of endocrine therapy and maximum duration of endocrine therapy. TTF was significantly longer in patients with less than two prior chemotherapy regimens (p = 0.0093), de novo metastatic disease (p = 0.0124) and without liver metastasis (p = 0.0024). We observed one case each of pulmonary infarction and psychiatric disorder.Fulvestrant is effective for ABC patients and may show greater efficacy in patients with few prior chemotherapy regimens, de novo metastatic disease and absence of liver metastasis. Prior endocrine therapy duration might not be a predictive factor for fulvestrant TTF in heavily treated ABC patients.

In a 68-year-old man on maintenance hemodialysis (HD), severe anemia was detected. Bone marrow biopsy was performed for investigation of pancytopenia and pathological examination revealed adenocarcinoma of the prostate. Prostate specific antigen (PSA) was 574 ng/mL. After androgen deprivation therapy was initiated, PSA decreased to 13.7 ng/mL. But subsequent elevation of PSA and pain due to bone metastases were recognized. Denosumab (120 mg) was administered. Although improvement of bone pain was observed, severe hypocalcemia occurred. Severe hypophosphatemia was subsequently detected. When we use denosumab in dialysis patients with advanced cancer, we should be careful of hypophosphatemia.

Tocilizumab (TCZ) is a humanized antihuman interleukin-6 (IL-6) receptor antibody used for the treatment of inflammatory diseases such as rheumatoid arthritis (RA). While TCZ could act as a therapeutic agent, it has a potential for inducing adverse drug events including psoriasis-like eruption. Seven cases with specific reference to TCZ-induced psoriasis eruption have been reported worldwide so far. In these cases, treatments with the same dosage of TCZ were either maintained or discontinued. Herein, we report a case involving a 74-year-old man diagnosed with rheumatoid factor-positive and anti-citrullinated protein antibody-positive RA with comorbidity of atopic dermatitis. TCZ was administered intravenously with oral methotrexate. After the third infusion, the patient developed TCZ-induced psoriasis-like eruptions, which were resolved by shortening the dose interval. Eruption recurrence was not observed after frequent TCZ subcutaneous injection. Our case may help physicians manage TCZ-induced psoriasis-like eruption.