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.

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.

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.

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.

Safety and immunogenicity of the COVID-19 vaccine BNT162b2 in patients undergoing chemotherapy for solid cancer.

BACKGROUND: Although COVID-19 severity in cancer patients is high, the safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients undergoing chemotherapy for solid cancers in Japan have not been reported. METHODS: We investigated the safety and immunogenicity of BNT162b2 in 41 patients undergoing chemotherapy for solid cancers and in healthy volunteers who received 2 doses of BNT162b2. We evaluated serum IgG antibody titers for S1 protein by ELISA at pre-vaccination, prior to the second dose and 14 days after the second vaccination in 24 cancer patients undergoing cytotoxic chemotherapy (CC group), 17 cancer patients undergoing immune checkpoint inhibitor therapy (ICI group) and 12 age-matched healthy volunteers (HV group). Additionally, inflammatory cytokine levels were compared between the HV and ICI groups at pre and the next day of each vaccination. RESULTS: Anti-S1 antibody levels were significantly lower in the ICI and CC groups than in the HV group after the second dose (median optimal density: 0.241 [0.063-1.205] and 0.161 [0.07-0.857] vs 0.644 [0.259-1.498], p = 0.0024 and p < 0.0001, respectively). Adverse effect profile did not differ among the three groups, and no serious adverse event occurred. There were no differences in vaccine-induced inflammatory cytokines between the HV and ICI groups. CONCLUSION: Although there were no significant differences in adverse events in three groups, antibody titers were significantly lower in the ICI and CC groups than in the HV group. Further protection strategies should be considered in cancer patients undergoing CC or ICI.

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

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

Phase I study of the antiprogrammed cell death-1 Ab spartalizumab (PDR001) in Japanese patients with advanced malignancies.

Spartalizumab is a humanized IgG4/κ mAb directed against human programmed cell death-1 (PD-1). In this phase I study, we investigated safety, pharmacokinetics, preliminary antitumor activity, and toxicity of spartalizumab in patients with advanced malignancies. Patients (n = 18) with a range of tumor types received spartalizumab i.v. at doses of 1, 3, and 10 mg/kg every 2 weeks until disease progression, unacceptable toxicity, or discontinuation at the discretion of the investigator or patient. Most patients (61%) had received five or more prior lines of therapy. No dose-limiting toxicities were reported and, hence, the maximum tolerated dose was 10 mg/kg or more. Pharmacokinetics in Japanese patients aligned with those reported in a global dose-escalation study. The safety profile was consistent with other approved anti-PD-1 mAbs; the most common drug-related adverse events were maculopapular rash (22%), followed by malaise and increased blood alkaline phosphatase (11% each). Partial responses were reported in two patients (11%), one with transitional cell carcinoma and the other with hepatocellular carcinoma. In conclusion, this study confirmed the safety of spartalizumab given at a dose of up to 10 mg/kg every 2 weeks in Japanese patients with cancers.

Induction chemotherapy in locally advanced squamous cell carcinoma of the head and neck.

In order to maximize the benefit of induction chemotherapy, practice based on a comprehensive interpretation of a large number of clinical trials, as in this review, is essential. The standard treatment for locally advanced squamous cell carcinoma of the head and neck is surgery or chemoradiation. However, induction chemotherapy followed by (chemo) radiotherapy may be used in some circumstances. Although many clinical trials of induction chemotherapy have been conducted, a rationale other than to preserve the larynx is still controversial. Selection of this modality should therefore be made with care. The current standard regimen for induction chemotherapy is docetaxel, cisplatin and 5-FU, but concerns remain about toxicity, cost and the duration of treatment. Regarding treatment after induction chemotherapy, it is also unclear whether radiation alone or chemoradiation is the better option. Furthermore, there is no answer as to what drugs should be used in combination with radiation therapy after induction chemotherapy. Several new induction chemotherapy treatment developments are currently underway, and future developments are expected. This review article summarizes the current position of induction chemotherapy for head and neck squamous cell carcinoma, based on the evidence produced to date, and discusses the future prospects for this treatment.

Immunotherapy for squamous cell carcinoma of the head and neck.

Squamous cell carcinoma of the head and neck is characterized by an immunosuppressive environment and evades immune responses through multiple resistance mechanisms. A breakthrough in cancer immunotherapy employing immune checkpoint inhibitors has evolved into a number of clinical trials with antibodies against programmed cell death 1 (PD-1), its ligand PD-L1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) for patients with squamous cell carcinoma of the head and neck. CheckMate141 and KEYNOTE-048 were practice-changing randomized phase 3 trials for patients with platinum-refractory and platinum-sensitive recurrent or metastatic squamous cell carcinoma of the head and neck, respectively. Furthermore, many combination therapies using anti-CTLA-4 inhibitors, tyrosine kinase inhibitors and immune accelerators are currently under investigation. Thus, the treatment strategy of recurrent or metastatic squamous cell carcinoma of the head and neck is becoming more heterogeneous and complicated in the new era of individualized medicine. Ongoing trials are investigating immunotherapeutic approaches in the curative setting for locoregionally advanced disease. This review article summarizes knowledge of the role of the immune system in the development and progression of squamous cell carcinoma of the head and neck, and provides a comprehensive overview on the development of immunotherapeutic approaches in both recurrent/metastatic and locoregionally advanced diseases.

A Phase II study of the safety and efficacy of lenvatinib in patients with advanced thyroid cancer.

AIM: To investigate the safety and efficacy of lenvatinib in advanced thyroid cancer. PATIENTS/METHODS: In this Phase II study, 51 Japanese patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC), medullary thyroid cancer (MTC) or anaplastic thyroid cancer (ATC) received once-daily lenvatinib 24 mg. The primary end point was safety. RESULTS: All patients experienced ≥1 adverse event (AE); only one patient experienced an AE leading to discontinuation. The most common any-grade AEs were hypertension, decreased appetite, palmar-plantar erythrodysesthesia, fatigue and proteinuria. Response rates for RR-DTC: 68%; MTC: 22%; ATC: 24%. Median progression-free survival for RR-DTC: 25.8 months; MTC: 9.2 months; ATC: 7.4 months. CONCLUSION: Lenvatinib demonstrated a manageable safety profile, proven antitumor activity in RR-DTC and promising efficacy in MTC and ATC. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov NCT01728623.

Nutritional support dependence after curative chemoradiotherapy in head and neck cancer: supplementary analysis of a phase II trial (JCOG0706S1).

OBJECTIVES: To explore the risk factors of laryngo-esophageal dysfunction-free survival and nutritional support dependence over 12 months in patients with unresectable locally advanced head and neck carcinomas who received chemoradiotherapy in a phase II trial of JCOG0706 (UMIN000001272). METHODS: Forty-five patients received radiation therapy for a total of 70 Gy/35fr concurrently with S-1 and cisplatin. Risk factors of laryngo-esophageal dysfunction-free survival and nutritional support dependence over 12 months were analyzed using Cox regression models and logistic regression models, respectively, with consideration to patient laboratory data just before chemoradiotherapy. Radiation fields were reviewed to analyze the relationship between the extent of the irradiated field and functional outcome. RESULTS: With a median follow-up period of 3.5 years, 3-year laryngo-esophageal dysfunction-free survival was 48.9%. For laryngo-esophageal dysfunction-free survival, hazards ratio of 2.35 in patients with nutritional support at registration (vs. without nutritional support; 95% confidence interval 0.96-5.76). For nutritional support dependence over 12 months, odds ratio was 6.77 in patients with hemoglobin less than the median of 13.4 g/dl (vs. higher than or equal to the median; 95% confidence interval 1.24-36.85) and was 6.00 in patients with albumin less than the median of 3.9 g/dl (vs. higher than or equal to the median; 95% confidence interval 1.11-32.54). Primary sites in disease-free patients with nutritional support dependence over 12 months were the oropharynx (N = 2) or hypopharynx (N = 1), and all pharyngeal constrictor muscles were included in irradiated fields with a curative dose. CONCLUSIONS: This supplementary analysis showed that pretreatment severe dysphagia requiring nutritional support, anemia and hypoalbuminemia might have a negative prognostic impact on long-term functional outcomes after curative chemoradiotherapy in head and neck cancer.

Expression of programmed death-1 in sentinel lymph nodes of breast cancer.

BACKGROUND AND OBJECTIVES: To explore whether lymphocytes in sentinel lymph nodes (SLNs) are highly exposed to tumor neoantigens and thus express high level of programmed death 1 (PD-1), we examined PD-1 expression in SLNs and non-sentinel regional lymph nodes (non-SLNs) in breast cancer. METHODS: We performed PD-1 immunohistochemistry in two cohorts: 40 metastasis-negative SLNs including 10 patients for each subtype (luminal A-like, luminal B-like, HER2, and triple negative breast cancer [TNBC]); and 25 pairs of metastasis-positive SLNs and non-SLNs (10 luminal A-like, 10 luminal B-like, and 5 TNBC). RESULTS: Among 40 metastasis-negative SLNs, 34 and 6 samples were PD-1 intensity grade 1 (low) and 2 (high), respectively. PD-1 intensity correlated with PD-1-positive lymphocyte numbers (P = 0.005); TNBC had the highest PD-1 lymphocyte numbers among all subtypes. The median PD-1-positive lymphocyte number was higher in SLNs than non-SLNs. In most cases, more lymphocytes in SLNs expressed PD-1 than those in non-SLNs (P < 0.0001). CONCLUSIONS: TNBC had the greatest PD-1 expression among all subtypes, and metastasis-positive SLNs had more PD-1-positive lymphocytes than downstream non-SLNs. These data suggested that lymphocytes in SLNs are activated following exposure to tumor neoantigens and thus tumor specific, and could be utilized as a biomarker platform.

Fluorescence fingerprint as an instrumental assessment of the sensory quality of tomato juices.

BACKGROUND: Sensory analysis is an important standard for evaluating food products. However, as trained panelists and time are required for the process, the potential of using fluorescence fingerprint as a rapid instrumental method to approximate sensory characteristics was explored in this study. RESULTS: Thirty-five out of 44 descriptive sensory attributes were found to show a significant difference between samples (analysis of variance test). Principal component analysis revealed that principal component 1 could capture 73.84 and 75.28% variance for aroma category and combined flavor and taste category respectively. Fluorescence fingerprints of tomato juices consisted of two visible peaks at excitation/emission wavelengths of 290/350 and 315/425 nm and a long narrow emission peak at 680 nm. The 680 nm peak was only clearly observed in juices obtained from tomatoes cultivated to be eaten raw. The ability to predict overall sensory profiles was investigated by using principal component 1 as a regression target. Fluorescence fingerprint could predict principal component 1 of both aroma and combined flavor and taste with a coefficient of determination above 0.8. CONCLUSION: The results obtained in this study indicate the potential of using fluorescence fingerprint as an instrumental method for assessing sensory characteristics of tomato juices.

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.

Analysis of thromboembolism and prognosis in metastatic pancreatic cancer from the Tokushukai REAl­world data project.

Cancer-associated thromboembolism (CAT), including venous thromboembolism (VTE) and arterial thromboembolism (ATE), is a frequent complication of advanced pancreatic cancer. However, reports on its incidence and clinical outcomes, especially on ATE, are limited. The present study aimed to investigate the incidence of CAT and its effects on overall survival in patients with metastatic pancreatic cancer. As part of the Tokushukai REAl-world data project in Japan, 846 eligible patients with metastatic pancreatic cancer treated with first-line chemotherapy were identified between April 2010 and March 2020. Using diagnosis procedure combination data from these patients, the present study investigated the incidence of VTE, ATE and cerebral and gastrointestinal bleeding requiring hospitalization. Blood laboratory data were collected within 14 days of the start of first-line treatment, and Khorana scores were calculated. The associations between CAT complications and comorbidities, concomitant medications and prognosis were examined. Among the 846 patients, 21 (2.5) and 70 (8.3%) had VTE and ATE, respectively (including five with overlapping VTE and ATE). CAT-positive patients had a significantly higher rate of gastrointestinal bleeding events compared with CAT-negative patients [13 of 86 (15.2%) vs. 46 of 760 (6.1%); P=0.01]. CAT-positive patients had a poorer prognosis [hazard ratio (HR), 1.28; 95% confidence interval (CI), 1.01-1.62] compared with CAT-negative patients, even after adjusting for background factors (HR, 1.20; 95% CI, 0.95-1.52). Cox regression analyses showed that higher Khorana scores were associated with significantly worse prognosis. This real-world data demonstrated that the incidence rate of CAT in patients with metastatic pancreatic cancer was 10.2%, and no statistically significant differences were observed, although there was a trend toward an adverse prognosis. The Khorana score may also be useful for predicting prognosis, even in the absence of CAT. This study was registered in the UMIN Clinical Trial Registry (http://www.umin.ac.jp/ctr/index.htm; clinical trial no. UMIN000050590).

Inflammation­based prognostic markers in patients with advanced or recurrent gastric cancer treated with nivolumab: Tokushukai REAl­world Data project 02 (TREAD 02).

In addition to blood test data, inflammation-based prognostic markers have been used to predict the prognosis of various types of cancer. However, several of these previous studies may be outdated, as they were conducted prior to the widespread adoption of immune checkpoint inhibitors, leading to limited reports on their efficacy. The present study aimed to assess the accuracy of different inflammation-based prognostic markers in patients with advanced or recurrent gastric cancer undergoing nivolumab monotherapy as salvage-line chemotherapy. In a retrospective cohort study across Japan, a total of 159 patients with advanced or recurrent gastric cancer who were treated with nivolumab between September 2017 and March 2020 were selected. Blood test data were collected within 14 days of the start of chemotherapy and 17 inflammation-based prognostic markers were evaluated. Cox regression analysis was performed using all patient background factors. Subsequently, model selection was performed using backward elimination based on the Akaike information criterion (AIC) to obtain effective background factors which could be assessed for their impact on patient survival. For each marker, the magnitude of the impact on the survival rate, after adjusting for the background factors, was assessed using concordance and AIC analyses. A total of 159 patients (female, 30.2%; median age, 70 years) were included in the present study. Most patients received platinum, fluoropyrimidine and taxane treatment, with a median of three prior lines of systemic therapy. With a median follow-up of 3.3 months (95% CI, 2.5-3.8), median overall survival and time to treatment failure were 3.8 months (95% CI, 3.3-4.5) and 1.8 months (95% CI, 1.8-2.3), respectively. Amongst the 17 markers analyzed, the modified Glasgow prognostic score (mGPS) was classed as the most useful factor that affected the survival rate of patients. Real-world data showed that mGPS, an inflammation-based prognostic marker, had the strongest correlation with prognosis in patients with advanced or recurrent gastric cancer receiving nivolumab monotherapy. The present study was registered as a clinical trial with the UMIN Clinical Trial Registry (http://www.umin.ac.jp/ctr/index.htm) under the trial registration number UMIN000050590 on 15th March 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.

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.