The cross-regional settlement methods in hospitals and the treatment-seeking behavior of patients with malignant tumors in China: an evolutionary game model.

Background: Cross-regional settlement management is a key indicator of national health insurance system maturity. Given the significant demand for cross-regional medical treatment among Chinese patients with malignant tumors and the territorially managed health insurance system, further research is necessary to explore the relationship between hospital settlement methods and treatment-seeking behaviors among these patients. This study introduces and validates an evolutionary game model that provides a theoretical foundation for direct settlement policies in cross-regional treatment. Methods: An evolutionary game model was constructed with patients and hospitals serving as strategic players within a dynamic system. This model integrates the patients' treatment utility, medical and nonmedical costs, and hospitals' financial and technological advancement benefits. Results: The evolutionary stability analysis revealed seven-game outcomes between hospitals and patients with malignant tumors. The numerical simulations suggest an evolutionary convergence toward strategy (1, 0), indicating a trend where patients with malignant tumors opt for cross-regional treatment, yet hospitals choose not to implement a direct settlement policy. Parameter sensitivity analysis showed that the parameters set in this study affected player behavioral choices and game equilibria. Conclusion: A strong demand for cross-regional medical treatment among Chinese patients with malignant tumors, and some hospitals require more incentives to implement cross-regional settlements. The key factors influencing the willingness of some patients with malignant tumors to resettle include the costs of in-area medical care, costs of cross-regional treatment without direct settlement, and the utility of cross-regional treatment. Technological advancement benefits and input costs influence some hospitals' motivation to adopt cross-regional settlements. Policy adjustments that effectively implement direct settlement policies can facilitate equilibrium, enhance the initiatives of some local health insurance management departments, improve the accessibility and efficiency of medical services, and reduce nonmedical expenses for patients.

Paraneoplastic Neurologic Disorders.

OBJECTIVE: This article reviews the clinical presentations, neural antibody associations, and oncologic accompaniments of paraneoplastic neurologic syndromes and neurologic autoimmunity in the context of immune checkpoint inhibitor (ICI) cancer immunotherapy. LATEST DEVELOPMENTS: Neural antibody discovery has improved the diagnosis of paraneoplastic neurologic syndromes. Neural antibodies also delineate the underlying disease pathophysiology and thus inform outcomes and treatments. Neural antibodies specific for extracellular proteins have pathogenic potential, whereas antibodies specific for intracellular targets are biomarkers of a cytotoxic T-cell immune response. A recent update in paraneoplastic neurologic syndrome criteria suggests high- and intermediate-risk phenotypes as well as neural antibodies to improve diagnostic accuracy in patients with paraneoplastic neurologic syndromes; a score was created based on this categorization. The introduction of ICI cancer immunotherapy has led to an increase in cancer-related neurologic autoimmunity with distinct clinical phenotypes. ESSENTIAL POINTS: Paraneoplastic neurologic syndromes reflect an ongoing immunologic response to cancer mediated by effector T cells or antibodies. Paraneoplastic neurologic syndromes can present with manifestations at any level of the neuraxis, and neural antibodies aid diagnosis, focus cancer screening, and inform prognosis and therapy. In patients with high clinical suspicion of a paraneoplastic neurologic syndrome, cancer screening and treatment should be undertaken, regardless of the presence of a neural antibody. ICI therapy has led to immune-mediated neurologic complications. Recognition and treatment lead to improved outcomes.

Evolving oncology care management trends in the United States: A survey among health care decision makers.

BACKGROUND: There is limited knowledge of how US managed care professionals view and prioritize quality metrics/performance measures, care models, alternative payment models, and clinical pathways in oncology settings. OBJECTIVE: To characterize payor perspectives on, and the use of, oncology clinical pathways and performance measures in their reimbursement/access decision-making process. METHODS: A survey was implemented via SurveyMonkey software and distributed electronically to a national sample of the Academy of Managed Care Pharmacy (AMCP) Market Insights Panel members from July 11 through August 5, 2022. The survey was created by a steering committee based on literature reviews of the current and future oncology care landscapes. The survey consisted of 47 questions, including those to establish respondents' position, responsibilities, and demographics. The results are presented as descriptive statistics for 7 key questions that covered the perceptions and use of quality metrics/performance measures, alternative payment models, and oncology care pathways as prioritized by the steering committee. RESULTS: Among the 695 AMCP panel members who were sent the survey, 73 responded (response rate 10.5%), 54 were eligible to continue, and 31 completed the entire questionnaire; the low response rate may limit generalizability of the survey results. Specific oncology clinical and economic measures of performance were currently used (70%-88%) but generally received less endorsement for future use (39%-49%) except for chemotherapy during end of life, which was considered for future use by 80% of respondents but was only currently used by 31%. Benchmarking was the primary reason for the use of performance measures; only 27% used these to inform value-based agreements. Real-world data tracked by respondents' institutions primarily focused on managed care and pharmacy utilization (39%-85%), with patient-reported and clinical outcomes tracked by only 17%-34%. Almost one-third (31%) did not use clinical oncology pathways, and among those who did, fewer than half (48%) reported that their organization tracks whether treatment decisions agree with the oncology care pathways, and only 26% reported feedback to oncology providers on how often their treatment decisions agree with the pathways. When considering alternative payment models, patient-related components received lower rankings in importance than clinical relevance, actionability, and costs. CONCLUSIONS: Variation among payors regarding current trends in oncology care management, including on the importance of patient-centric outcomes and the use of oncology clinical pathways, suggests the need to focus on value-based health care and greater uptake of oncology clinical pathways.

Experiences and Satisfaction With Telehealth During the COVID-19 Pandemic: The Perspectives of Patients With Cancer in Australia.

PURPOSE: There has been a significant rise in telehealth consultations across Australia since COVID-19 was declared a worldwide pandemic. We aimed to obtain patient feedback on telehealth, identify key strengths and weaknesses, and assess the feasibility of telehealth beyond the pandemic. METHODS: A survey was developed to obtain patient feedback on telehealth. Patients attending medical oncology clinics at St George Hospital and Sutherland Hospital from April 1, 2020, to May 31, 2020, were identified. Patients who were reviewed via phone or videoconference were included in this study. Eligible patients were texted or emailed a survey link within a week of their telehealth consultation. Surveys were anonymous and completion of the survey implied informed consent. Patients who did not have a mobile number or e-mail were excluded from this study. RESULTS: One thousand fifty-nine patients were reviewed during the study period, of whom 644 (60%) were reviewed via telehealth. The survey response rate was 36.3% (230 patients responded of 634 surveys sent). Ten telehealth patients did not have a mobile number or email and were excluded. Sixty-seven percent of telehealth consults were for active surveillance, 31% for prechemotherapy/treatment reviews, 1.6% for best supportive care, and 0.5% for new consults. Seventy percent of patients were satisfied that their medical needs were met via telehealth. Ninety percent wanted another telehealth consult, and 73% wanted telehealth to continue post resolution of the pandemic. Minimizing risk of exposure to COVID-19 and patient convenience were identified as key strengths of telehealth while absence of physical examination was the main disadvantage. CONCLUSION: Majority of the patients surveyed were satisfied that telehealth safely met their medical needs. There is a considerable demand for telehealth to continue beyond the pandemic.

Dose selection of novel anticancer drugs: exposing the gap between selected and required doses.

Historically, dose selection of anticancer drugs has mainly been based on establishing the maximum tolerated dose in phase 1 clinical trials with a traditional 3 plus 3 design. In the era of targeted therapies and immune-modulating agents, this approach does not necessarily lead to selection of the most favourable dose. This strategy can introduce potentially avoidable toxicity or inconvenience for patients. Multiple changes in drug development could lead to more rational dose selection, such as use of better predictive preclinical models, adaptive and randomised trial design, evaluation of multiple dose levels in late-phase development, assessment of target activity and saturation, and early biomarker use for efficacy and safety evaluation. In this Review, we evaluate the rationale and validation of dose selection in each phase of drug development for anticancer drugs approved by the European Medicines Agency and US Food and Drug Administration from Jan 1, 2020, to June 30, 2023, and give recommendations for dose optimisation to improve safety and patient convenience. In our evaluation, we classified 20 (65%) of the 31 recently registered anticancer agents as potential candidates for dose optimisation, which could be achieved either by reducing the dose (n=10 [32%]) or adjusting the dosage regimen (n=10 [32%]). Dose selection seemed to be adequately justified for nine (29%) of the drugs, whereas the reviewed data were inconclusive for formulating a recommendation on dose optimisation for two (6%) of the drugs.

Radiotherapy, immunity, and immune checkpoint inhibitors.

Radiotherapy exerts immunostimulatory and immunosuppressive effects, both locally, within the irradiated tumour microenvironment, and systemically, outside the radiation field. Inspired by preclinical data that showed synergy between radiotherapy and immune checkpoint inhibitors, multiple clinical trials were initiated with the hypothesis that combined treatment with radiotherapy and immune checkpoint inhibitors could stimulate a robust systemic immune response and improve clinical outcomes. However, despite early optimism, radioimmunotherapy trials in the curative and metastatic settings have met with little success. In this Review, we summarise the immunostimulatory effects of radiotherapy that provided the theoretical basis for trials of combination radiotherapy and immune checkpoint inhibitors. We also discuss findings from clinical trials incorporating radiotherapy and immune checkpoint inhibitors and examine the success of these trials in the context of the immunosuppressive effects of radiotherapy. We conclude by highlighting targets for relieving radiotherapy-induced immunosuppression with the goal of enhancing the combined effects of radiotherapy and immune checkpoint inhibitors.

WRN Helicase: Is There More to MSI-H than Immunotherapy?

In this issue, Picco and colleagues provide further evidence that WRN inhibitors are synthetically lethal in microsatellite instability-high (MSI-H) cancers and function by blocking the helicase domain of select WRN residues. They demonstrate that WRN inhibitors may be even more effective in a subset of MSI-high tumors with (TA)n repeat expansions, which represents a possible strategy in clinical development. See related article by Picco et al., p. 1457 (1).

Iron: The Secret Ingredient Breaking PARPi Resistance.

PARP inhibitors (PARPi) are used as a first-line treatment option for cancers with BRCA1/2 mutations, yet a significant number of patients show a limited response to these agents. In the present study, Lei and colleagues demonstrate that PARPi promote increased ferroptosis sensitivity and this can be exploited therapeutically to improve the response to PARPi, marking an important therapeutic concept to exploit ferroptosis-based strategies in clinical settings. See related article by Lei et al., p. 1476 (2).

Interactions Between Oral Microbiota and Cancers in the Aging Community: A Narrative Review.

The oral microbiome potentially wields significant influence in the development of cancer. Within the human oral cavity, an impressive diversity of more than 700 bacterial species resides, making it the second most varied microbiome in the body. This finely balanced oral microbiome ecosystem is vital for sustaining oral health. However, disruptions in this equilibrium, often brought about by dietary habits and inadequate oral hygiene, can result in various oral ailments like periodontitis, cavities, gingivitis, and even oral cancer. There is compelling evidence that the oral microbiome is linked to several types of cancer, including oral, pancreatic, colorectal, lung, gastric, and head and neck cancers. This review discussed the critical connections between cancer and members of the human oral microbiota. Extensive searches were conducted across the Web of Science, Scopus, and PubMed databases to provide an up-to-date overview of our understanding of the oral microbiota's role in various human cancers. By understanding the possible microbial origins of carcinogenesis, healthcare professionals can diagnose neoplastic diseases earlier and design treatments accordingly.

Interactions between oral microbiota shifts and cancer: The oral microbiome potentially wields significant influence in the development of cancer. Within the human oral cavity, an impressive diversity of more than 700 bacterial species resides, making it the second most varied microbiome in the body. This finely balanced oral microbiome ecosystem is vital for sustaining oral health. However, disruptions in this equilibrium, often brought about by dietary habits and inadequate oral hygiene, can result in various oral ailments like periodontitis, cavities, gingivitis, and even oral cancer. There is compelling evidence that the oral microbiome is linked to several types of cancer, including oral, pancreatic, colorectal, lung, gastric, and head and neck cancers. This review discussed the critical connections between cancer and members of the human oral microbiota. Extensive searches were conducted across the Web of Science, Scopus, and PubMed databases to provide an up-to-date overview of our understanding of the oral microbiota's role in various human cancers. By understanding the possible microbial origins of carcinogenesis, healthcare professionals can diagnose neoplastic diseases earlier and design treatments accordingly.

Mushrooms and Their Compounds with Potential Anticancer Activity: A Review.

Mushrooms produce many metabolites that show biological activity, which can be obtained from their fruiting body, mycelium or recovered from the culture broth when mushrooms are grown in submerged fermentation. Mushrooms are a source of natural pharmaceuticals; they have been reported to have potential inhibitory or preventive activity against some diseases, including different types of cancer. Cancer represents one of the main causes of death worldwide. It is worth mentioning that despite advances in pharmacological treatments, they still present side effects in patients. In this sense, the study of the use of mushrooms in complementary treatments against cancer is of great interest. Based on studies carried out in vitro and, in some cases, using animal models, it has been observed that mushrooms present preventive, corrective, and therapeutic properties against different types of cancer, by stimulating the immune system, due to their antioxidant, antimutagenic, and anti-inflammatory activities, as well as the regulation of the expression of some cellular processes, cell cycle arrest, and apoptosis, etc. Based on the above, this manuscript shows a review of scientific studies that support the anticancer activity of some mushrooms and/or their bioactive compounds.

Negative association of steroids with immunotherapy efficacy in a multi-tumor cohort: time and dose-dependent.

Previous studies have suggested a negative impact of steroids on the efficacy of immune checkpoint inhibitors (ICI), but how this effect is modulated by the dosage and time of administration is yet to be clarified. We have performed a retrospective analysis of 475 patients with advanced solid tumors treated with ICI as monotherapy from 2015 to 2022. Data regarding immune-related adverse events (irAEs) and clinical outcomes were collected. For each patient, the daily steroid dose (in mg/kg of prednisone) was registered until disease progression or death. The impact of cumulative doses on response rates and survival outcomes was analyzed within different periods. The objective response rate (ORR) was significantly lower among patients exposed to steroids within 30 days before the first cycle of ICI (C1) (20.3% vs. 36.7%, p < 0.01) and within the first 90 days of treatment (25.7% vs. 37.7%, p = 0.01). This negative association was confirmed by multivariable analysis. Higher mean steroid doses were observed among non-responders, and cumulative doses were inversely correlated with the disease control rate (DCR) around ICI initiation. Remarkably, poorer outcomes were observed even in patients belonging to the lowest dose quartile compared to the steroid-naïve population. The exposure to steroids after 6 months of ICI was not associated with worse survival outcomes. Our results suggest that the potential impact of steroids on ICI efficacy may be time-dependent, prevailing around ICI initiation, and dose-dependent, with modulation of neutrophil-to-lymphocyte ratio as a possible underlying mechanism.