Validity of a single-item indicator of treatment side effect bother in a diverse sample of cancer patients

Purpose With higher efficacy of cancer therapies, the numbers and types of side effects experienced by patients have also increased, evidencing a need for brief assessments of side effect bother. The Functional Assessment of Cancer Therapy-General (FACT-G) includes the item “I am bothered by side effects of treatment” (GP5). This study aimed to confirm GP5’s validity in a large, diverse, real-world patient sample. Methods Real-world data were drawn from 10 Adelphi Disease Specific Programmes (DSP™) conducted between 2015 and 2019 in France, Germany, Italy, Spain, the UK and the USA, covering 10 cancer sites. We examined correlations between GP5 responses and varied measures of patient-reported global health and the number of side effects experienced. We explored whether more advanced patients and those with worse Eastern Cooperative Oncology Group Performance Status Rating (ECOG PSR) reported greater side effect bother. Finally, we conducted differential item functioning (DIF) assessment using the Mantel–Haenszel approach. Results The sample included 6755 advanced cancer patients. GP5 responses were distributed similarly across most cancer sites. A moderate, negative correlation (rpolyserial = − 0.43) between GP5 responses and global health evidenced convergent validity. Known groups validity was evidenced by dichotomised distributions of GP5, showing expected results between cancer stage 2 vs. 3 and 4 and with ECOG PSR (p < 0.001). Little evidence of DIF was found. Conclusion GP5 exhibited evidence of validity across cancer sites and countries and appeared to measure the same construct across these countries. GP5 has significant promise as a summary indicator of side effect bother.

Cisplatin and Irinotecan as First-Line Chemotherapy for Previously Untreated Metastatic Thymic Carcinoma: Updated Analysis

Platinum-based chemotherapy is the de facto standard treatment for metastatic or unresectable thymic carcinoma. The optimal chemotherapy regimen has not yet been determined, including whether this should be combined with a second- or third-generation anti-cancer agent. We retrospectively evaluated the data of patients with metastatic or unresectable thymic carcinoma who were treated with a combination of cisplatin and irinotecan as first-line chemotherapy between 2002 and 2021 (trial registration UMIN000012175). The primary endpoint was response rate according to the RECIST criteria version 1.1. Secondary endpoints were disease control rate, progression-free survival (PFS), overall survival (OS), and toxicity (adverse events). Some patients analyzed in this study were also included in the previous trial, which was terminated early. For this analysis, we included 18 patients with a median age of 56 years and an Eastern Cooperative Oncology Group performance status of 0 or 1. All patients had clinical stage IVa or IVb thymic carcinoma according to the Masaoka-Koga staging system. The response rate was 44% and the disease control rate was 89%. The median PFS was 8.4 months (95% confidence interval (CI): 2.7–11.6 months) and the median OS was 45.6 months (95% CI: 15.7–69.1 months). Grade 3 or worse hematological toxicity was observed in 5 patients and grade 3 or worse non-hematological toxicity was observed in 3 patients. None of the patients developed febrile neutropenia, and no treatment-related deaths occurred. Thus, the combination of cisplatin and irinotecan as first-line chemotherapy for metastatic thymic carcinoma showed efficacy and acceptable toxicity.

Diversity, Trust and Conformity: a Simulation Study

Previous simulation models have found positive effects of cognitive diversity on group performance, but have not explored effects of diversity in demographics (e.g., gender, ethnicity). In this paper, we present an agent-based model that captures two empirically supported hypotheses about how demographic diversity can improve group performance. The results of our simulations suggest that, even when social identities are not associated with distinctive task-related cognitive resources, demographic diversity can, in certain circumstances, benefit collective performance by counteracting two types of conformity that can arise in homogeneous groups: those relating to group-based trust and those connected to normative expectations towards in-groups.

Prognostic nomogram for patients with unresectable pancreatic cancer treated with gemcitabine plus nab–paclitaxel or FOLFIRINOX: A post–hoc analysis of a multicenter retrospective study in Japan (NAPOLEON study)

Background No reliable nomogram has been developed until date for predicting the survival in patients with unresectable pancreatic cancer undergoing treatment with gemcitabine plus nab–paclitaxel (GnP) or FOLFIRINOX. Methods This analysis was conducted using clinical data of Japanese patients with unresectable pancreatic cancer undergoing GnP or FOLFIRINOX treatment obtained from a multicenter study (NAPOLEON study). A Cox proportional hazards model was used to identify the independent prognostic factors. A nomogram to predict 6–, 12–, and 18–month survival probabilities was generated, validated by using the concordance index (C–index), and calibrated by the bootstrapping method. And then, we attempted risk stratification for survival by classifying the patients according to the sum of the scores on the nomogram (total nomogram points). Results A total of 318 patients were enrolled. A prognostic nomogram was generated using data on the Eastern Cooperative Oncology Group performance status, liver metastasis, serum LDH, serum CRP, and serum CA19–9. The C–indexes of the nomogram were 0.77, 0.72 and 0.70 for 6–, 12–, and 18–month survival, respectively. The calibration plot showed optimal agreement at all points. Risk stratification based on tertiles of the total nomogram points yielded clear separations of the survival curves. The median survival times in the low–, moderate–, and high–risk groups were 15.8, 12.8 and 7.8 months (P<0.05), respectively. Conclusions Our nomogram might be a convenient and inexpensive tool to accurately predict survival in Japanese patients with unresectable pancreatic cancer undergoing treatment with GnP or FOLFIRINOX, and will help clinicians in selecting appropriate therapeutic strategies for individualized management.

Clinical features as potential prognostic factors in patients treated with nivolumab for highly pretreated metastatic gastric cancer: a multicenter retrospective study

Background Although nivolumab (anti-programmed cell death-1 antibody) is a promising approach for advanced gastric cancer (AGC), the response rate remains limited. The aim of this multicenter retrospective study was to determine if clinical features could serve as prognostic factors of the efficacy of nivolumab in patients with AGC. Methods Fifty-eight patients with AGC who were treated with nivolumab as a third or later line from October 2017 to December 2018 at any of five clinical sites were enrolled in the study. The correlation between the best overall response and clinical features was investigated. Overall survival and progression-free survival after initiation of nivolumab were calculated and clinical features that could be predictors of the prognosis were sought. Results The disease control rate (DCR) for nivolumab was 36.2% and was significantly correlated with performance status (p = 0.021), metastasis to one organ (p = 0.006), and grade 2 or higher immune-related adverse events (p = 0.027). There was also a significant association between response to nivolumab and ability to receive subsequent chemotherapy (p = 0.022). In the analysis of overall survival, the following variables were identified as being significantly associated with a poor outcome: Eastern Cooperative Oncology Group performance status ≥1, prior treatment with trastuzumab, no immune-related adverse events, lack of a response to nivolumab, and inability to receive subsequent chemotherapy. Conclusion The findings of this study suggest that nivolumab may be ineffective for AGC in patients with poor performance status and those with a history of treatment with trastuzumab.

Daratumumab plus lenalidomide and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: frailty subgroup analysis of MAIA

In the phase 3 MAIA study of patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM), daratumumab plus lenalidomide/dexamethasone (D-Rd) improved progression-free survival (PFS) versus lenalidomide/dexamethasone (Rd). We present a subgroup analysis of MAIA by frailty status. Frailty assessment was performed retrospectively using age, Charlson comorbidity index, and baseline Eastern Cooperative Oncology Group performance status score. Patients were classified as fit, intermediate, non-frail (fit + intermediate), or frail. Of the randomized patients (D-Rd, n = 368; Rd, n = 369), 396 patients were non-frail (D-Rd, 196 [53.3%]; Rd, 200 [54.2%]) and 341 patients were frail (172 [46.7%]; 169 [45.8%]). After a 36.4-month median follow-up, non-frail patients had longer PFS than frail patients, but the PFS benefit of D-Rd versus Rd was maintained across subgroups: non-frail (median, not reached [NR] vs 41.7 months; hazard ratio [HR], 0.48; P < 0.0001) and frail (NR vs 30.4 months; HR, 0.62; P = 0.003). Improved rates of complete response or better and minimal residual disease (10–5) negativity were observed for D-Rd across subgroups. The most common grade 3/4 treatment-emergent adverse event in non-frail and frail patients was neutropenia (non-frail, 45.4% [D-Rd] and 37.2% [Rd]; frail, 57.7% and 33.1%). These findings support the clinical benefit of D-Rd in transplant-ineligible NDMM patients enrolled in MAIA, regardless of frailty status.

Emotion Recognition From Speech Using Perceptual Filter and Neural Network

This chapter on multi speaker independent emotion recognition encompasses the use of perceptual features with filters spaced in Equivalent rectangular bandwidth (ERB) and BARK scale and vector quantization (VQ) classifier for classifying groups and artificial neural network with back propagation algorithm for emotion classification in a group. Performance can be improved by using the large amount of data in a pertinent emotion to adequately train the system. With the limited set of data, this proposed system has provided consistently better accuracy for the perceptual feature with critical band analysis done in ERB scale.

The new scientific and methodological model of creating a digital health passport for monitoring physical and mental state and physical preparedness of comprehensive school students

School nowadays is focused on students’ health as a prerequisite for a successful performance. The health status is a multifaceted concept which is gauged by various indicators. Determining the health status of children takes a lot of time resources on the part of educational staff engaged in systemizing and analysing the data and making practical recommendations for optimising students’ health. Boosting the quality of health monitoring can be achieved via modern IT systems by creating a digital health passport for school students. This research is based on the methods of theoretical analysis, synthesis, data generalisation, analytical modelling of the content and organisational process of health monitoring via modern information technology. An attempt was made to create a scientific and methodological model for collating and evaluating data on school children’s physical health, mental health and physical preparedness. The data are presented in the form of a digital health passport. The data were used as a basis for the computer programme The Health Passport which allows the user to obtain information on the general health status and differentiated aspects of health, such as physical or mental health and physical preparedness. The programme can also give individualised practical recommendations by analysing the test results; store statistically relevant information on individual and group performance; conduct comparative analysis of individual and group performance of comprehensive school students on the methodological basis of mathematical statistics.

Efficacy and Safety of Chemoradiation Therapy Using One- Shot Cisplatin via Hepatic Arterial Infusion for Advanced Hepatocellular Carcinoma with Major Macrovascular Invasion: a Single-arm Retrospective Cohort Study

Background: Patients with hepatocellular carcinoma (HCC) and macrovascular invasion (MVI) who receive systemic chemotherapy have a poor prognosis. This study aimed to determine if one-shot cisplatin (CDDP) chemotherapy via hepatic arterial infusion (HAI) combined with radiation therapy (RT) prior to systemic chemotherapy could improve the outcomes of these patients. Methods: This study consisted of 32 HCC patients with the following eligibility criteria: (i) portal vein invasion 3/4 and/or hepatic vein invasion 2/3; (ii) received one-shot CDDP via HAI; (iii) received RT for MVI, (iv) a Child-Pugh score ≤7; and (v) an Eastern Clinical Oncology Group Performance Status score of 0 or 1. To determine the therapeutic effect, we collect the information of patients’ characteristics and took contrast-enhanced computed tomography at the start of the therapy and every 2 to 4 months after the therapy initiated. We evaluated the overall response of the tumor and tumor thrombosis according to modified Response Evaluation Criteria in Solid Tumors. We assessed the patient’s data statistically by the Mann-Whitney U-test, fisher’s exact test, and evaluated overall survival and progress-free survival by log-ranked test, and analyzed the predictive factors by as appropriate. Results: The overall response rate at the first evaluation performed a median of 1.4 weeks after HAI was 16% of the main intrahepatic tumor and 59% of the MVI. The best responses were the same as those of the first-time responses. The duration of median survival was 8.6 months, and for progression-free survival of the main intrahepatic tumor was 3.2 months. The predictive factor of overall survival was the relative tumor volume in the liver and the first therapeutic response of MVI. There were no severe adverse events or radiation-induced hepatic complications. Conclusions: One-shot CDDP via HAI and RT were well tolerated and showed immediate and favorable control of MVI. Thus, this combination shows potential as a bridging therapy to systemic chemotherapy.

Sex-Based Clinical Outcome in Advanced NSCLC Patients Undergoing PD-1/PD-L1 Inhibitor Therapy—A Retrospective Bi-Centric Cohort Study

Men with non-small cell lung cancer (NSCLC) have a more favorable response to immune-checkpoint inhibitor (ICI) monotherapy, while women especially benefit from ICI-chemotherapy (CHT) combinations. To elucidate such sex differences in clinical practice, we retrospectively analyzed two cohorts treated with either ICI monotherapy (n = 228) or ICI-CHT combination treatment (n = 80) for advanced NSCLC. Kaplan–Meier analyses were used to calculate progression-free (PFS) and overall survival (OS), influencing variables were evaluated using Cox-regression analyses. No significant sex differences for PFS/OS could be detected in either cohort. Men receiving ICI monotherapy had a statistically significant independent impact on PFS by Eastern Cooperative Oncology Group performance status (ECOG) ≥2 (hazard ratio (HR) 1.90, 95% confidence interval (CI): 1.10–3.29, p = 0.021), higher C-reactive protein (CRP; HR 1.06, 95%CI: 1.00–1.11, p = 0.037) and negative programmed death-ligand 1 (PD-L1) status (HR 2.04, 95%CI: 1.32–3.15, p = 0.001), and on OS by CRP (HR 1.09, 95%CI: 1.03–1.14, p = 0.002). In men on ICI-CHT combinations, multivariate analyses (MVA) revealed squamous histology (HR 4.00, 95%CI: 1.41–11.2, p = 0.009) significant for PFS; and ECOG ≥ 2 (HR 5.58, 95%CI: 1.88–16.5, p = 0.002) and CRP (HR 1.19, 95%CI: 1.06–1.32, p = 0.002) for OS. Among women undergoing ICI monotherapy, no variable proved significant for PFS, while ECOG ≥ 2 had a significant interaction with OS (HR 1.90, 95%CI 1.04–3.46, p = 0.037). Women treated with ICI-CHT had significant MVA findings for CRP with both PFS (HR 1.09, 95%CI: 1.02–1.16, p = 0.007) and OS (HR 1.11, 95%CI: 1.03–1.19, p = 0.004). Although men and women responded similarly to both ICI mono- and ICI-CHT treatment, predictors of response differed by sex.