Ira Jacobs

Background: Cancer cachexia describes the muscle and weight loss, anorexia, and physical impairment common in certain adult cancers. No formal criteria exist to define paediatric cancer cachexia, making its clinical recognition and impact largely unknown. Using established undernutrition guidelines, criteria were developed to identify potential cachexia in children with cancer based on standardised anthropometric measures or diagnostic codes. Methods: The Surveillance, Epidemiology, and End Results and Optum Electronic Health Records databases were used to estimate prevalence and incidence rates of cancer and cancer cachexia between 2017 and 2021 in patients aged < 20 and < 18 years, respectively. In the absence of a consensus definition for paediatric cachexia, four sets of candidate criteria were developed based on body weight for length/height or body mass index z‐scores, or reduced gain or loss of body weight, corresponding to mild or severe undernutrition. A fifth criterion required a potentially cachexia‐related ICD‐10‐CM diagnosis code. Results: This study included 26,855 paediatric patients (aged < 18 years) with cancer; ~90% were aged ≥ 2 years. Epidemiologic estimates for cancer cachexia prevalence and incidence rate varied considerably by age, cancer type and cachexia definition. Estimates were low for most categories, especially in the youngest age groups; however, cachexia was difficult to assess in patients aged < 2 years due to small patient numbers. Conclusions: We describe one of the first attempts to develop potential paediatric cachexia criteria. These criteria and resulting data provide a framework to inform further research into generating consensus guidelines for the identification of childhood cancer cachexia.

Aims: We assessed care in cancer patients with cachexia across leading health systems (LHSs). Patients & methods: Qualitative interviews and quantitative surveys were conducted with LHSs executives and frontline health care personnel, representing 46 total respondents and 42 unique LHSs and including oncology service line leaders, supportive care services, dietitians and surgical oncologists. Results: Cachexia was not considered a top priority, and formal diagnoses were rare. Participants highlighted the importance of addressing barriers to increase clinical trial enrollment and support frontline health care personnel and patients in early detection of cachexia. Conclusion: Cachexia prioritization needs to be elevated across LHSs executives to obtain capital and strategic imperatives to advance related care.

Aim: Understanding factors that shape leading health systems' (LHS) perspectives around heart failure (HF) treatment. Patients & methods: First of its kind study using a cross-sectional, descriptiv... Plain language summary What is this summary about? We interviewed frontline healthcare workers (such as doctors and nurses) as well as executives at large US health systems to understand how they t... Tweetable abstract A survey of frontline healthcare workers and executives from large health systems showed there are opportunities to improve heart failure treatment and become more comprehensive ...

Background: The COVID-19 pandemic accelerated drivers for virtual health adoption and triggered the US federal government to implement regulatory changes to reduce barriers to virtual health implementation. Consequently, virtual health solutions have been increasingly adopted, and health systems in the United States have been reorganizing their care delivery process with unprecedented speed. Objective: This study aimed to assess and make recommendations on the strategy, business model, implementation, and future considerations for scaling and sustaining virtual health solutions based on the views of executives from the largest health systems in the United States. Methods: In September 2020 and October 2020, the Health Management Academy conducted 29 quantitative surveys and 23 qualitative interviews involving 58 executives from 41 of the largest health systems in the United States. Participating health systems were approximately equally distributed across size categories (small, medium, and large, defined as annual total operating revenue US $2-3 billion, $3-6 billion, and >$6 billion, respectively) and US Census Bureau regions (Northeast, Midwest, South, and West). Results: Based on the Health Management Academy’s assessment of approaches to governance, financing, data infrastructure, and clinical integration of virtual health, most participating health systems (13/24, 54%) had a mid-stage level of maturity in virtual health implementation. Executives reported the pandemic is forcing health systems to re-examine strategic priorities; the most commonly raised key impacts were increased access (15/21, 71%) and flexibility (10/21, 48%) as well as lower costs of care delivery (9/21, 43%). Most executives (16/28, 57%) reported their organization had a defined budget for virtual health, and many noted that virtual health is best supported through value-based payment models. Irrespective of health system maturity, reimbursement was consistently rated as a key challenge to virtual health scaling, along with patient access to and understanding of virtual health technology. The success of virtual health implementation was most commonly measured by patient satisfaction, health care provider engagement, and proportion of health care providers using virtual health solutions (reported by 7/8, 88%; 6/8, 75%; and 7/8, 75% of information technology executives, respectively). Almost all health systems (27/29, 93%) expect to continue growing their virtual health offerings for the foreseeable future, with user-friendliness and ease of integration into the electronic medical record as key factors in making go-forward decisions on virtual health solutions (each selected by 9/10, 90% executives). Conclusions: The increased demand for virtual health solutions during the COVID-19 pandemic is expected to continue postpandemic. Consequently, health systems are re-evaluating their current platforms, processes, and strategy to develop a sustainable, long-term approach to virtual health. To ensure future success, health system leaders need to proactively build on their virtual health solutions; advocate for payment, site flexibility, and reimbursement parity for virtual health; and demonstrate continued engagement and boldness to evolve care beyond established models.

BACKGROUND The COVID-19 pandemic accelerated drivers for virtual health adoption and triggered the US federal government to implement regulatory changes to reduce barriers to virtual health implementation. Consequently, virtual health solutions have been increasingly adopted, and health systems in the United States have been reorganizing their care delivery process with unprecedented speed. OBJECTIVE This study aimed to assess and make recommendations on the strategy, business model, implementation, and future considerations for scaling and sustaining virtual health solutions based on the views of executives from the largest health systems in the United States. METHODS In September 2020 and October 2020, the Health Management Academy conducted 29 quantitative surveys and 23 qualitative interviews involving 58 executives from 41 of the largest health systems in the United States. Participating health systems were approximately equally distributed across size categories (small, medium, and large, defined as annual total operating revenue US $2-3 billion, $3-6 billion, and >$6 billion, respectively) and US Census Bureau regions (Northeast, Midwest, South, and West). RESULTS Based on the Health Management Academy’s assessment of approaches to governance, financing, data infrastructure, and clinical integration of virtual health, most participating health systems (13/24, 54%) had a mid-stage level of maturity in virtual health implementation. Executives reported the pandemic is forcing health systems to re-examine strategic priorities; the most commonly raised key impacts were increased access (15/21, 71%) and flexibility (10/21, 48%) as well as lower costs of care delivery (9/21, 43%). Most executives (16/28, 57%) reported their organization had a defined budget for virtual health, and many noted that virtual health is best supported through value-based payment models. Irrespective of health system maturity, reimbursement was consistently rated as a key challenge to virtual health scaling, along with patient access to and understanding of virtual health technology. The success of virtual health implementation was most commonly measured by patient satisfaction, health care provider engagement, and proportion of health care providers using virtual health solutions (reported by 7/8, 88%; 6/8, 75%; and 7/8, 75% of information technology executives, respectively). Almost all health systems (27/29, 93%) expect to continue growing their virtual health offerings for the foreseeable future, with user-friendliness and ease of integration into the electronic medical record as key factors in making go-forward decisions on virtual health solutions (each selected by 9/10, 90% executives). CONCLUSIONS The increased demand for virtual health solutions during the COVID-19 pandemic is expected to continue postpandemic. Consequently, health systems are re-evaluating their current platforms, processes, and strategy to develop a sustainable, long-term approach to virtual health. To ensure future success, health system leaders need to proactively build on their virtual health solutions; advocate for payment, site flexibility, and reimbursement parity for virtual health; and demonstrate continued engagement and boldness to evolve care beyond established models.

Aim: To provide an assessment of published literature on the demographic representation in Phase I trials of biopharmaceutical oncology agents. Materials & methods: We conducted a rapid evidence as... Lay abstract A plain language version of this article is available and is published alongside the paper online: www.futuremedicine.com/doi/suppl/10.2217/fon-2020-1262

Objective: To investigate patient-reported outcome (PRO) usage in phase I oncology clinical trials, including types of PRO measures and changes over time. Methods: We analyzed ClinicalTrials.gov records of phase I oncology clinical trials completed by December 2019. Results: Of all eligible trials, 2.3% (129/5,515) reported ≥1 PRO, totaling 181 instances of PRO usage. PRO usage increased over time, from 0.6% (trials initiated before 2000) to 3.4% (trials starting between 2015 and 2019). The most common PRO measures were unspecified (29%), tumor-specific (24%), and generic cancer (19%). Conclusion: Although uncommon in phase I oncology clinical trials, PRO usage is increasing over time. PRO measures were often unspecified on ClinicalTrials.gov, suggesting that more precise reporting and standardization are needed.

The immunologic landscape of the host and tumor play key roles in determining how patients will benefit from immunotherapy, and a better understanding of these factors could help inform how well a tumor responds to treatment. Recent advances in immunotherapy and in our understanding of the immune system have revolutionized the treatment landscape for many advanced cancers. Notably, the use of immune checkpoint inhibitors has demonstrated durable responses in various malignancies. However, the response to such treatments is variable and currently unpredictable, the availability of predictive biomarkers is limited, and a substantial proportion of patients do not respond to immune checkpoint therapy. Identification and investigation of potential biomarkers that may predict sensitivity to immunotherapy is an area of active research. It is envisaged that a deeper understanding of immunity will aid in harnessing the full potential of immunotherapy, and allow appropriate patients to receive the most appropriate treatments. In addition to the identification of new biomarkers, the platforms and assays required to accurately and reproducibly measure biomarkers play a key role in ensuring consistency of measurement both within and between patients. In this review we discuss the current knowledge in the area of peripheral immune-based biomarkers, drawing information from the results of recent clinical studies of a number of different immunotherapy modalities in the treatment of cancer, including checkpoint inhibitors, bispecific antibodies, chimeric antigen receptor T cells, and anti-cancer vaccines. We also discuss the various technologies and approaches used in detecting and measuring circulatory biomarkers and the ongoing need for harmonization.

Summary: Background In pancreatic ductal adenocarcinoma (PDAC), the chemokine (C-C motif) ligand 2 (CCL2)/chemokine (C-C motif) receptor 2 (CCR2) axis plays a key role in immunosuppressive properties of the tumor microenvironment, patient prognosis, and chemoresistance. This phase Ib study assessed the effects of the orally administered CCR2 inhibitor PF-04136309 in combination with nab-paclitaxel and gemcitabine in patients with previously untreated metastatic PDAC. Methods Patients received PF-04136309 twice daily (BID) continuously plus nab-paclitaxel (125 mg/m²) and gemcitabine (1000 mg/m²) administered on days 1, 8, and 15 of each 28-day cycle. The primary objectives were to evaluate safety and tolerability, characterize dose-limiting toxicities (DLTs), and determine the recommended phase II dose (RP2D) of PF-04136309. Results In all, 21 patients received PF-04136309 at a starting dose of 500 mg or 750 mg BID. The RP2D was identified to be 500 mg BID. Of 17 patients treated at the 500 mg BID starting dose, three (17.6%) experienced a total of four DLTs, including grade 3 dysesthesia, diarrhea, and hypokalemia and one event of grade 4 hypoxia. Relative to the small number of patients (n = 21), a high incidence (24%) of pulmonary toxicity was observed in this study. The objective response rate for 21 patients was 23.8% (95% confidence interval: 8.2–47.2%). Levels of CD14 + CCR2+ inflammatory monocytes (IM) decreased in the peripheral blood, but did not accumulate in the bone marrow. Conclusions PF-04136309 in combination with nab-paclitaxel plus gemcitabine had a safety profile that raises concern for synergistic pulmonary toxicity and did not show an efficacy signal above nab-paclitaxel and gemcitabine. ClinicalTrials.gov identifier: NCT02732938.

The increasing use of multiple immunomodulatory (IMD) agents for cancer therapies (e.g. antibodies targeting immune checkpoints, bispecific antibodies, and chimeric antigen receptor [CAR]-T cells), is raising questions on their potential immunogenicity and effects on treatment. In this review, we outline the mechanisms of action (MOA) of approved, antibody-based IMD agents, potentially related to their immunogenicity, and discuss the reported incidence of anti-drug antibodies (ADA) as well as their clinical relevance in patients with cancer. In addition, we discuss the impact of the administration route and potential strategies to reduce the incidence of ADA and manage treated patients. Analysis of published reports indicated that the risk of immunogenicity did not appear to correlate with the MOA of anti-programmed death 1 (PD-1)/PD-ligand 1 monoclonal antibodies nor to substantially affect treatment with most of these agents in the majority of patients evaluated to date. Treatment with B-cell depleting agents appears associated with a low risk of immunogenicity. No significant difference in ADA incidence was found between the intravenous and subcutaneous administration routes for a panel of non-oncology IMD antibodies. Additionally, while the data suggest a higher likelihood of immunogenicity for antibodies with T-cell or antigen-presenting cell (APC) targets versus B-cell targets, it is possible to have targets expressed on APCs or T cells and still have a low incidence of immunogenicity.