Risk prediction model for cisplatin-induced acute kidney injury in patients with head and neck cancer receiving chemoradiotherapy: A re-analysis of a phase II/III JCOG1008 trial.

OBJECTIVES: Acute kidney injury (AKI) represents a major toxicity associated with cisplatin. We developed a risk prediction model for cisplatin-induced AKI in patients with postoperative high-risk head and neck cancer who received chemoradiotherapy during a randomized phase II/III trial, JCOG1008. MATERIALS AND METHODS: Two hundred and fifty-one patients received radiotherapy with weekly cisplatin at 40 mg/m2 (weekly arm) or 3-weekly cisplatin at 100 mg/m2 (3-weekly arm). AKI was defined using the AKI Network classification/staging system as increased serum creatinine of ≥0.3 mg/dL or a ≥1.5-fold increase from baseline 30 days after completing chemoradiotherapy. The Akaike information criterion was used to explore the optimal model by combining explanatory variables at registration. RESULTS: Among the 251 patients (210 men and 41 women (median age; 62 years)), 94 (37.5 %) developed cisplatin-induced AKI. The optimal cisplatin-induced AKI risk prediction model comprised four factors, including a primary site of hypopharynx/larynx (vs. oral cavity/oropharynx), 3-weekly arm (vs. weekly arm), serum albumin of ≤3.5 g/dL (vs. >3.5 g/dL) and creatinine clearance (CCr) of <90 mL/min (vs. ≥90 mL/min). The incidence of cisplatin-induced AKI rose with cumulative count of the four factors. When the cumulative count was ≥2, the positive predictive value for cisplatin-induced AKI was 50.3 %. CONCLUSIONS: We developed a risk prediction model for cisplatin-induced AKI in patients with head and neck cancer who received postoperative chemoradiotherapy using primary site, cisplatin administration method, serum albumin, and CCr. Patients with risk factors unrelated to the cisplatin administration method should adopt a weekly cisplatin regimen.

Efficacy of Short-Course Antibiotic Therapy for Acute Cholangitis With Positive Blood Cultures: A Retrospective Study.

BACKGROUND: Short-term treatment of acute cholangitis is sufficient for cure compared with the standard treatment duration. Whether this short-course antimicrobial therapy is effective in patients with acute cholangitis with positive blood cultures has not been fully investigated. This study assessed whether patients with acute cholangitis could achieve successful outcomes with a three-day or shorter antimicrobial treatment period, even with a positive blood culture. METHODS: This single-center retrospective study involved patients with acute cholangitis, defined according to the Tokyo Guidelines 2018 for any cause, who underwent successful biliary drainage and completed a seven-day or shorter antimicrobial treatment. Patients were categorized into six groups based on the duration of antibiotic use (short or standard) after endoscopic retrograde cholangiopancreatography and blood culture findings (positive, negative, or no collection). The primary outcome was the clinical cure rate, defined as no initial presenting symptoms by day 14 after biliary drainage and no recurrence or death by day 30. Secondary outcomes included a three-month recurrence rate and length of hospital stay. RESULTS: In total, 389 cases were selected, and 27 patients (6.9%) undergoing short-course therapy tested positive for blood culture. The clinical cure rate (n=25, 92.6%) in this group was comparable to that in the other groups. For the three-month recurrence rate (n=1, 3.7%) and median hospital stay (six days), this group's outcomes were either better or similar to those of the other groups. CONCLUSIONS: For cases of successful drainage in acute cholangitis, even with positive blood cultures, short-term antibiotic therapy may be appropriate.

Prognostic impact of concomitant pH-regulating drugs in patients with non-small cell lung cancer receiving epidermal growth factor receptor tyrosine kinase inhibitors: the Tokushukai REAl-world Data project 01-S1.

PURPOSE: This study aimed to examine the prognostic impact of concomitant pH-regulating drug use in patients with epidermal growth factor receptor (EGFR)-mutation-positive non-small-cell lung cancer (NSCLC) receiving EGFR-tyrosine kinase inhibitors (TKIs). METHODS: We conducted a nationwide retrospective cohort study and reviewed clinical data of consecutive patients with NSCLC treated with the first-line EGFR-TKIs in 46 hospitals between April 2010 and March 2020. Cox regression analyses were conducted to examine the differences in overall survival (OS) between patients treated with and without concomitant pH-regulating drugs, including potassium-competitive acid blockers (P-CABs), proton pump inhibitors (PPIs), and H2-receptor antagonists (H2RAs). RESULTS: A total of 758 patients were included in the final dataset, of which 307 (40%) were administered concomitant pH-regulating drugs while receiving frontline EGFR-TKIs. After adjusting for basic patient characteristics, patients administered gefitinib, erlotinib, afatinib, and osimertinib with concomitant pH-regulating drugs had lower OS than those without concomitant pH-regulating drugs, with hazard ratios of 1.74 (with a 95% confidence interval of 1.34-2.27), 1.33 (0.80-2.22), 1.73 (0.89-3.36), and 5.04 (1.38-18.44), respectively. The 2-year OS rates of patients receiving gefitinib with or without concomitant pH-regulating drugs were 65.4 and 77.5%, those for erlotinib were 55.8 and 66.6%, and those for afatinib were 63.2 and 76.9%, respectively. The 1-year OS rates of patients receiving osimertinib with or without concomitant pH-regulating drugs were 88.1% and 96.9%, respectively. CONCLUSION: In addition to the first-generation EGFR-TKIs, the second- and third-generation EGFR-TKIs also resulted in OS deterioration in patients with EGFR mutation-positive NSCLC when used concurrently with pH-regulating drugs.

Antimicrobial therapy outcomes in acute cholangitis: Hilar multiple obstructions versus single hilar and common bile duct obstructions.

Background and Aim: The appropriate duration of antimicrobial therapy for acute cholangitis (AC) arising from multiple hilar biliary obstructions as opposed to simple obstruction in the extrahepatic bile duct has not been established. This study assessed the efficacy of the duration of antimicrobial treatments in the Tokyo Guidelines 2018 for AC based on the cause and site of obstruction. Methods: This single-center retrospective study involved patients with AC who underwent successful biliary drainage and completed a 7-day or shorter antimicrobial treatment. Patients were categorized into three groups: Group 1, bile duct stone or benign obstruction; Group 2, simple biliary obstruction due to malignancy; and Group 3, multiple hilar biliary obstruction due to malignancy. The primary outcome was clinical cure rate, and the secondary outcomes were 3-month recurrence rate and length of hospital stay. Results: A total of 373 patients were selected. Patients in Group 3 were younger or had Charlson Comorbidity Index ≥4, and had fewer positive blood cultures. In Group 3, the clinical cure rate (87.1%) and 3-month recurrence rate (32.3%) were less favorable than those in the other groups. In Group 1, the clinical cure rate was significantly higher (98.1%, P = 0.02) with a much lower 3-month recurrence rate of only 3.4% (P < 0.001) than that in the other groups. The median hospital stay for all groups was 7 days. Conclusion: This study suggests that the outcomes in Group 3 may be worse than those in Groups 1 or 2, regardless of the duration of the antibiotic treatment.

Expression of EGFR and p16 in Squamous Cell Carcinoma of External Auditory Canal.

The expression of EGFR and p16 in the external auditory canal squamous cell carcinoma (EACSCC) and their impacts on oncological outcomes were not well studied. Seventeen-one consecutive patients who were treated for EACSCC at Kobe University Hospital from 1995 to 2018 were enrolled in this study. The expression of EGFR, and p16 were evaluated and their impacts on oncological outcomes were statistically analyzed. Positive expression of EGFR was observed in 62 patients (87%). Strong positive expression of p16 were observed in 18 patients (32.4%), and weakly positive expression in 30 patients (42.3%), respectively. While the number of the patients with negative EGFR expression were limited, all the surgically treated patients with negative EGFR expression have been alive without disease. In the patients with T3 & T4a EACSCC, prognosis of the patients with positive p16 expression EACSCC tended to be better than those with negative p16 expression. These results suggest the clinical significance of EGFR and p16 expressions in the patients with advanced EACSCC to predict oncological outcomes.

Inflammation­based prognostic markers of metastatic pancreatic cancer using real­world data in Japan: The Tokushukai REAl­world Data (TREAD) project.

Inflammation-based prognostic markers based on a combination of blood-based parameters, including the modified Glasgow prognostic score (mGPS), have been associated with clinical outcomes in patients with various types of cancer. The present study aimed to evaluate and compare the accuracy of these previously reported markers in patients with metastatic pancreatic cancer receiving first-line chemotherapy. A total of 846 patients were identified between April 2010 and March 2020 as part of a nationwide real-world study from 46 Tokushukai medical group hospitals in Japan. Blood laboratory data collected within 14 days of starting first-line chemotherapy assessed 17 inflammation-based prognostic markers. Information from patients with no missing data was used to compare the accuracy and performance of the inflammation-based prognostic markers. A total of 487 patients were eligible for this supplemental analysis. The 17 inflammation-based markers demonstrated significant prognostic value. Among them, the concordance rate with overall survival (OS) was highest for mGPS. The median OS time of patients with mGPS 0, 1 and 2 was 8.2, 6.0 and 2.9 months, respectively. Compared with mGPS 0, mGPS 1 and 2 showed hazard ratios of 1.39 (95% confidence interval, 1.07-1.81) and 2.63 (2.00-3.45), respectively. The present real-world data analysis showed that various previously reported inflammation-based markers had significant prognostic value in patients with metastatic pancreatic cancer. Among these markers, the mGPS demonstrated the highest level of accuracy. This trial has been registered in the University Hospital Medical Information Network Clinical Trials Registry as UMIN000050590 on April 1, 2023.

Association of short-course antimicrobial therapy and bacterial resistance in acute cholangitis: Retrospective cohort study.

Background and study aims Although the number of resistant bacteria tends to increase with prolonged antimicrobial therapy, no studies have examined the relationship between the duration of antimicrobial therapy and increase in the number of resistant bacteria in acute cholangitis. We hypothesized that the short-term administration of antimicrobial agents in acute cholangitis would suppress bacterial resistance. Patients and methods This was a single-center, retrospective, observational study of patients with acute cholangitis admitted between January 2018 and June 2020 who met the following criteria: successful biliary drainage, positive blood or bile cultures, bacteria identified from cultures sensitive to antimicrobials, and subsequent cholangitis recurrence by January 2022. The patients were divided into two groups: those whose causative organisms at the time of recurrence became resistant to the antimicrobial agents used at the time of initial admission (resistant group) and those who remained susceptible (susceptible group). Multivariate analysis was used to examine risk factors associated with the development of resistant pathogens. Multivariate analysis investigated antibiotics used with the length of 3 days or shorter after endoscopic retrograde cholangiopancreatography (ERCP) and previously reported risk factors for the development of bacterial resistance. Results In total, 89 eligible patients were included in this study. There were no significant differences in patient background or ERCP findings between the groups. The use of antibiotics, completed within 3 days after ERCP, was associated with a lower risk of developing bacterial resistance (odds ratio, 0.17; 95% confidence interval, 0.04-0.65; P =0.01). Conclusions In acute cholangitis, the administration of antimicrobials within 3 days of ERCP may suppress the development of resistant bacteria.

Real-world treatment outcomes of metastatic biliary tract cancer patients in Japan: the Tokushukai REAl-world data project 04 (TREAD 04).

OBJECTIVES: To investigate temporal trends in treatment patterns and prognostic factors for overall survival in patients with metastatic biliary tract cancer. METHODS: From the Tokushukai REAl-world Data project, we identified 945 patients with metastatic biliary tract cancer treated with gemcitabine, tegafur/gimeracil/oteracil, gemcitabine plus cisplatin, gemcitabine plus tegafur/gimeracil/oteracil or gemcitabine plus cisplatin and tegafur/gimeracil/oteracil between April 2010 and March 2022. Stratified/conventional Cox regression analyses were conducted to examine the association between overall survival and patient- and tumour-related factors, study period, hospital volume, hospital type and first-line chemotherapy regimen. Using inverse probability of treatment weighting with propensity scores, overall survival was also compared between monotherapy and combination therapy groups. RESULTS: We enrolled 366 patients (199 men; median age, 72 years). Over a median follow-up of 5.2 months, the median overall survival was 7.0 months (95% confidence interval 6.2-9.0), and the median time to treatment failure was 3.5 months (95% confidence interval 3.1-4.5). Median overall survival and time to treatment failure for gemcitabine/tegafur-gimeracil-oteracil/gemcitabine plus cisplatin/gemcitabine plus tegafur-gimeracil-oteracil/gemcitabine plus cisplatin and tegafur-gimeracil-oteracil regimen were 6.2/6.6/7.9/16.2/15.1 and 2.8/3.4/4.1/15.3/7.4 months, respectively. Primary disease site, previous surgery, previous endoscopic procedures and hospital type were identified as significant prognostic factors. Inverse probability of treatment weighting analysis demonstrated that combination therapy had a significantly better prognosis than monotherapy (hazard ratio 0.61, 95% confidence interval 0.43-0.88, P = 0.006). CONCLUSIONS: Our real-world data analysis showed that standard care for metastatic biliary tract cancer is widely used in hospitals throughout Japan and verified the survival benefits of combination therapy over monotherapy observed in prior clinical trials. CLINICAL TRIAL NUMBER: UMIN000050590 (http://www.umin.ac.jp/ctr/index.htm).

Stepwise prolongation of overall survival from first to third generation EGFR-TKIs for EGFR mutation-positive non-small-cell lung cancer: the Tokushukai REAl-world Data project (TREAD 01).

OBJECTIVE: The introduction of new-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has afforded promising overall survival outcomes in clinical trials for non-small-cell lung cancer. We aim to investigate the current adoption rate of these agents and the real-world impact on overall survival among institutions. METHODS: In a nationwide retrospective cohort study of 46 Tokushukai Medical Group hospitals in Japan, we analyzed clinical data of consecutive patients with non-small-cell lung cancer receiving EGFR-TKIs between April 2010 and March 2020. Univariate and multivariate Cox regression analyses examined the associations between overall survival and patient/tumor-related factors and first-line EGFR-TKIs. RESULTS: A total of 758 patients (58.5% females; median age, 73 years) were included. Of 40 patients diagnosed in 2010, 72.5% received gefitinib, whereas 81.3% of 107 patients diagnosed in 2019 received osimertinib as the first-line EGFR-TKI. With a median follow-up of 15.8 months, the median overall survival was 28.4 months (95% confidence interval, 15.3-31.0). In a multivariate Cox regression analysis, age, body mass index, disease status, EGFR mutational status and first-line epidermal growth factor receptor tyrosine kinase inhibitor were identified as significant prognostic factors after adjusting for background factors including study period, hospital volume and hospital type. The estimated 2-year overall survival rates for gefitinib, erlotinib, afatinib and osimertinib were 70.1% (95% confidence interval 59.7-82.4), 67.8% (95% confidence interval 55.3-83.2), 75.5% (95% confidence interval 64.7-88.0) and 90.8% (95% confidence interval 84.8-97.3), respectively. The median time to treatment failure of gefitinib, erlotinib, afatinib and osimertinib were 12.8, 8.8, 12.0 and 16.9 months or more, respectively. CONCLUSIONS: Our real-world data revealed that the swift and widespread utilization of newer-generation EGFR-TKIs in patients with EGFR mutation-positive non-small-cell lung cancer, and that these newer-generation EGFR-TKIs can prolong overall survival regardless of hospital volume or type. Therefore, osimertinib could be a reasonable first choice treatment for these patients across various clinical practice settings.

Real­world treatment outcomes among patients with metastatic pancreatic cancer in Japan: The Tokushukai real­world data project.

The present study aimed to investigate temporal trends in treatment patterns and prognostic factors for overall survival (OS) among patients with metastatic pancreatic cancer. From the Tokushukai REAl-world Data project, 1,093 patients with metastatic pancreatic cancer treated with gemcitabine, tegafur/gimeracil/oteracil (S-1), gemcitabine plus S-1, gemcitabine plus nab-paclitaxel, or fluorouracil, folic acid, oxaliplatin and irinotecan (FOLFIRINOX) between April 2010 and March 2020 were identified. Stratified/conventional Cox regression analyses were conducted to examine associations between patient- and tumor-related factors, study period, hospital volume, hospital type and first-line chemotherapy regimens. Overall, 846 patients were selected (503 male patients; median age, 70 years) after excluding ineligible patients. Over a median follow-up of 5.4 months, the median OS was 6.8 months (95% confidence interval, 6.3-7.4). The median OS for gemcitabine, S-1, gemcitabine plus S-1, gemcitabine plus nab-paclitaxel and FOLFIRINOX regimens was 5.9, 5.3, 7.7, 9.0 and 9.5 months, respectively. The median OS for 2010-2013, 2014-2017 and 2017-2020 was 6.2, 7.1 and 7.8 months, respectively. Performance status, body mass index and first-line chemotherapy regimens were identified to be significant prognostic factors. In summary, the real-world data indicated that standard care, including chemotherapy, for metastatic pancreatic cancer was widely used in hospitals throughout Japan and verified the survival benefits of gemcitabine plus nab-paclitaxel and FOLFIRINOX observed in prior clinical trials. This trial has been registered in the University Hospital Medical Information Network Clinical Trials Registry as UMIN000050590 on April 1, 2023.

Safety and Accuracy of Professional Continuous Glucose Monitoring in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.

Hyperglycemia in the early days following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a well-known risk factor for acute graft-versus-host disease (GVHD) and non-relapse mortality. The FreeStyle Libre Pro, a factory calibrated continuous glucose monitoring (CGM) device, has been used for the retrospective analysis of glucose testing in patients with diabetes. We assessed the safety and accuracy of the device in patients undergoing allo-HSCT. We recruited eight patients who underwent allo-HSCT between August 2017 and March 2020. They wore the FreeStyle Libre Pro on the day before or on the day of transplantation until 28 days after transplantation. Adverse events, especially bleeding and infection, were monitored to assess safety, and blood glucose levels were measured and compared with the device values. None of the eight participants experienced bleeding that was difficult to stop from the sensor site or local infection that required antimicrobial administration. The device value was well correlated with blood glucose (correlation coefficient r=0.795, P<0.01); however, the overall mean absolute relative difference was 32.1%±16.0%. Our study demonstrated the safety of FreeStyle Libre Pro in allo-HSCT patients. However, the sensor results tended to be lower than the blood glucose levels.

Response to mRNA SARS-CoV-2 vaccination evaluated by B-cell receptor repertoire after tixagevimab/cilgavimab administration.

The use of anti-SARS-CoV-2 antibody products like tixagevimab/cilgavimab represents an important strategy to protect immunocompromised patients with haematological malignancies from COVID-19. Although patients who receive these agents should still be vaccinated, the use of tixagevimab/cilgavimab can mask the production of anti-spike antibody after vaccination, making it hard to assess vaccine response. We have newly established a quantification method to assess the response to SARS-CoV-2 vaccination at the mRNA level using B-cell receptor (BCR) repertoire assay and the Coronavirus Antibody Database (CoV-AbDab). Repeated blood samples before and after vaccination were analysed for the BCR repertoire, and BCR sequences were searched in the database. We analysed the number and percentage frequency of matched sequences. We found that the number of matched sequences increased 2 weeks after the first vaccination and quickly decreased. Meanwhile, the number of matched sequences more rapidly increased after the second vaccination. These results show that the postvaccine immune response can be assessed at the mRNA level by analysing the fluctuation in matching sequences. Finally, BCR repertoire analysis with CoV-AbDab clearly demonstrated the response to mRNA SARS-CoV-2 vaccination even after tixagevimab/cilgavimab administration in haematological malignancy patients who underwent allogeneic haematopoietic stem cell transplantation.

Real-World Outcomes of Systemic Therapy in Japanese Patients with Cancer (Tokushukai REAl-World Data Project: TREAD): Study Protocol for a Nationwide Cohort Study.

Cohort studies using large-scale databases have become increasingly important in recent years. The Tokushukai Medical Group is a leading medical group in Japan that includes 71 general hospitals nationwide from Hokkaido to Okinawa, with a total of 18,000 beds, and a unified electronic medical record system. This retrospective cohort study aims to evaluate the real-world outcomes of systemic therapy for Japanese patients with cancer using this merit of scale. All adult patients with cancer who received systemic therapy using a centrally registered chemotherapy protocol system at 46 hospitals from April 2010 to March 2020 will be identified (~48,850 patients). Key exclusion criteria include active double cancer and inadequate data extraction. Data will be obtained through electronic medical records, diagnosis procedure combination data, medical prescription data, and the national cancer registration system that includes sociodemographic variables, diagnostic and laboratory tests, concomitant drug prescriptions, cost, and overall survival. Kaplan-Meier estimates will be calculated for time-to-event analyses. Stratified/conventional Cox proportional hazards regression analyses will be conducted to examine the relationships between overall survival and related factors. Our findings provide important insights for future research directions, policy initiatives, medical guidelines, and clinical decision-making.

Promising Efficacy of a Third Dose of mRNA SARS-CoV-2 Vaccination in Patients Treated with Anti-CD20 Antibody Who Failed 2-Dose Vaccination.

Anti-CD20 antibodies react with CD20 expressed not only on malignant B cells, but also on normal B cells. It has been reported that patients treated with anti-CD20 antibodies had an insufficient response to two-dose mRNA SARS-CoV-2 vaccination. To investigate the efficacy of a third dose in these patients, we investigated serum IgG antibody titers for the S1 protein after a third vaccination in 22 patients treated with the anti-CD20 antibody who failed two-dose vaccination. Results showed that overall, 50% of patients seroconverted. Although no patient who received the third dose within 1 year of the last anti-CD20 antibody administration showed an increase in S1 antibody titer, 69% of patients who received the third dose more than 1 year after the last anti-CD20 antibody administration seroconverted. Our data show that a third dose of vaccination is effective in improving the seroconversion rate in patients treated with the anti-CD20 antibody who failed standard two-dose vaccination.

Transition of the PD-1 occupancy of nivolumab on T cells after discontinuation and response of nivolumab re-challenge.

Although nivolumab is administered every two or four weeks, high programmed cell death-1 (PD-1) binding of nivolumab on T cells lasting for several months has been reported. A relationship between the PD-1 occupancy rate on T-cells and the efficacy of nivolumab is not yet fully understood. The present study used flow cytometric analyses to determine the time-dependence of PD-1 occupancy in five patients who discontinued nivolumab. The relationship between PD-1 occupancy at relapse and the efficacy of re-challenge was also studied. Occupancies after discontinuation were measured at a total of 32 points. The data indicated that it took 32.4 and 48.9 weeks to decrease occupancy by 50 and 70%, respectively. Subsequently, two patients had recurrence and were re-challenged with nivolumab. At that time, one patient had 70.8% occupancy while the other had 6.6%. Treatment was effective only for the patient with lower occupancy. Overall, the present study suggests that re-challenge with nivolumab may be efficacious in patients with low occupancy at recurrence.

Human papillomavirus-related oropharyngeal carcinoma.

It was not until around 2000 that human papillomavirus-related oropharyngeal carcinoma was recognized as carcinoma with clinical presentations different from nonrelated head and neck carcinoma. Twenty years after and with the revision of the tumor-node-metastasis classification in 2017, various clinical trials focused on human papillomavirus-related oropharyngeal carcinoma to improve the prognosis and quality of life of patients with this disease. However, the incidence of human papillomavirus-related cancers is increasing, which is expected to be particularly prominent in Japan, where human papillomavirus vaccination is not widely available. In this review, we describe the current status of clinical trials (mainly focused on initial surgery and radiation dose reduction) for, primary and secondary prevention of, and the present status of human papillomavirus-related oropharyngeal carcinoma in Japan.

Identification of Breast Cancer Stem Cells Using a Newly Developed Long-acting Fluorescence Probe, C5S-A, Targeting ALDH1A1.

BACKGROUND/AIM: Aldehyde dehydrogenase (ALDH) 1A1 is a well-known marker for cancer stem cells (CSCs), characterized by self-renewal capacity and multidrug resistance in breast cancer. We developed a near-infrared turn-on fluorescence probe for ALDH1A1, C5S-A, which is suitable for observing and analyzing viable cells. Here, we demonstrated the utility of C5S-A in CSC research using breast cancer cell lines. MATERIALS AND METHODS: To evaluate concordance between C5S-A and conventional stem cell markers, breast cancer cells sorted for ALDEFLUOR-positive cells and for CD44+/CD24- cell populations were stained with C5S-A. Tumorigenicity of C5S-A-positive cells was examined by mammosphere formation assay and subcutaneous transplantation to immunodeficient mice. Additionally, to determine how long fluorescence from a single staining remained observable, we cultured breast cancer cells for 5 days after C5S-A staining. We then evaluated whether C5S-A-positive cells possessed resistance to cytotoxic drugs by chronological imaging. RESULTS: C5S-A staining showed good concordance with conventional breast CSC markers, and good utility for research into CSC characteristics in breast cancer cell lines, including tumorigenesis. Additionally, C5S-A was observable for more than 3 days with a single staining. Using this property, we then confirmed that C5S-A-positive cells possessed resistance to cytotoxic drugs, which is one of the characteristics of CSCs. CONCLUSION: We showed that C5S-A is suitable for CSC research using breast cancer cell lines, and confirmed its utility in observing cells over time.

Management of elderly patients with head and neck cancer.

There are no established guidelines for managing older patients with head and neck cancer. Most clinical trials that define current standard therapy included few elderly patients. On the other hand, there is great variability in patients' comorbidities, physical functions, cognitive function, familial and financial background and values. The key point appears to be appropriate geriatric assessment, clarifying the patients' outcomes and a multidisciplinary team approach, including the treatment decision-making policy. Although these processes should be scientific in nature, the evidence for the treatment of elderly head and neck patients is very limited. This review summarizes the evidence available regarding the management of geriatric assessment, each treatment modality and the multidisciplinary team approach for older patients with head and neck cancers.

Systemic therapy for salivary gland malignancy: current status and future perspectives.

Salivary gland malignancies are rare neoplasms that have a broad histological spectrum and a variety of biologic behaviors. Salivary gland malignancies are known as chemo-resistant tumors, which render optimal treatment challenging. This review summarizes the role of systemic therapy for salivary gland malignancies. To date, the advantage of adding concurrent chemotherapy has remained undefined for both postoperative and inoperable locally advanced salivary gland malignancy patients undergoing radiotherapy. For recurrent/metastatic disease, local and/or systemic treatment options should be discussed in a multidisciplinary setting with consideration to both patient needs and tumor factors. For symptomatic patients or those who may compromise organ function, palliative systemic therapy can be a reasonable option based on the results of phase II studies. Platinum combination regimens as first-line therapy have been widely accepted. Personalized therapies have become established options, particularly for androgen receptor-positive, HER2-positive and NTRK fusion-positive salivary gland malignancies (i.e. androgen receptor and HER2 in salivary duct carcinoma and NTRK3 in secretory carcinoma). For patients with adenoid cystic carcinoma, multi-targeted tyrosine kinase inhibitors have also been developed. Anti-PD1 checkpoint inhibitors have shown limited activity to date. Investigation of active systemic treatments for salivary gland malignancy remains a significant unmet need. Future directions might include a more comprehensive genomic screening approach (usually next-generation sequencing-based) and combination strategies using immune checkpoint inhibitors. These are rare malignancies that require ongoing effort in the conduct of high-quality clinical trials.

Limited increase in antibody titers following mRNA SARS-CoV-2 vaccination for more than 3 years after final dose of anti-CD20 antibody.

We investigated the efficacy of BNT162b2 mRNA COVID-19 vaccine in patients with B-cell malignancies treated with anti-CD20 antibody. Although T-cell-mediated immune responses were detected even in patients receiving R-CHOP treatment, the S1 antibody titer following BNT162b2 vaccination remained only marginally increased for more than 3 years after the final dose of anti-CD20 antibody. We found no relationship between the percent of B-cells and S1 antibody titer. The duration of this suppression was much longer than we anticipated. Further protection and treatment strategies against COVID-19 for these patients are warranted.