Diagnosis of Metastatic Non-Small Cell Lung Cancer during Hospitalization: Missed Opportunity for Optimal Supportive Care?

PURPOSE: The usual workup for patients newly diagnosed with advanced non-small cell lung cancer (NSCLC) occurs in the ambulatory setting. A subset of patients present with acute care needs and receive the diagnosis while hospitalized. Palliative therapies are typically initiated when patients are outpatients, even when diagnoses are made when they are inpatients. Lengthy admission, rehabilitation needs after discharge, and readmissions are possible barriers to timely and adequate outpatient follow-up. The outcomes for these patients diagnosed in the hospital are not well characterized. We hypothesized that patients have been ill-served by current treatment patterns, as reflected by low rates of cancer-directed treatment and poor survival. PATIENTS AND METHODS: We performed a retrospective study of new inpatient diagnoses of metastatic NSCLC at our institution between 1 January 2012 and 1 January 2022. The primary outcome was the proportion of patients ultimately receiving cancer-directed therapy. Other outcomes included time to treatment, use of targeted therapy, palliative care/hospice utilization, and overall survival (OS). RESULTS: Seventy-three patients were included, with a median age of 57 years. Twenty-seven patients (37%) ultimately received systemic therapy with a median time from diagnosis to treatment of 37.5 days. Overall, 5.4% patients died while admitted, 6.8% were discharged to a hospice, 21.9% were discharged to a facility, and 61.6% were discharged home. Only 20 patients (27%) received palliative care consultation. The median OS for our entire population was 2.3 months, with estimated 6-month and 1-year OS rates of 32% and 22%, respectively. CONCLUSION: Patients with new inpatient diagnoses of metastatic NSCLC have extremely poor outcomes. Current management strategies resulted in few patients starting systemic therapy, yet most of the patients did not receive palliative care or hospice involvement. These findings demonstrate that there is a high unmet need to optimally support and palliate these patients.

Defining the Role of the Gut Microbiome in the Pathogenesis and Treatment of Lymphoid Malignancies.

The gut microbiome is increasingly being recognized as an important immunologic environment, with direct links to the host immune system. The scale of the gut microbiome's genomic repertoire extends the capacity of its host's genome by providing additional metabolic output, and the close communication between gut microbiota and mucosal immune cells provides a continued opportunity for immune education. The relationship between the gut microbiome and the host immune system has important implications for oncologic disease, including lymphoma, a malignancy derived from within the immune system itself. In this review, we explore past and recent discoveries describing the role that bacterial populations play in lymphomagenesis, diagnosis, and therapy. We highlight key relationships within the gut microbiome-immune-oncology axis that present exciting opportunities for directed interventions intended to shape the microbiome for therapeutic effect. We conclude with a limited summary of active clinical trials targeting the microbiome in hematologic malignancies, along with future directions on gut microbiome investigations within lymphoid malignancies.

Precision Medicine in Myeloid Malignancies: Hype or Hope?

PURPOSE OF REVIEW: We review how understanding the fitness and comorbidity burden of patients, and molecular landscape of underlying acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) at the time of diagnosis is now integral to treatment. RECENT FINDINGS: The upfront identification of patients' fitness and molecular profile facilitates selection of targeted and novel agents, enables risk stratification, allows consideration of allogeneic hematopoietic cell transplantation in high-risk patients, and provides treatment selection for older (age ≥ 75) or otherwise unfit patients who may not tolerate conventional treatment. The use of measurable residual disease (MRD) assessment improves outcome prediction and can also guide therapeutic strategies such as chemotherapy maintenance and transplant. In recent years, several novel drugs have received FDA approval for treating patients with AML with or without specific mutations. A doublet and triplet combination of molecular targeted and other novel treatments have resulted in high response rates in early trials. Following the initial success in AML, novel drugs are undergoing clinical trials in MDS. Unprecedented advances have been made in precision medicine approaches in AML and MDS. However, lack of durable responses and long-term disease control in many patients still present significant challenges, which can only be met, to some extent, with innovative combination strategies throughout the course of treatment from induction to consolidation and maintenance.

Determinants of ten-year overall survival of acute myeloid leukemia: a large national cancer database analysis.

Clinical trials do not routinely capture long-term overall survival (OS) in acute myeloid leukemia (AML). We utilized a large National Cancer Database (NCDB) to determine different factors affecting 10-year OS in AML. For patients, 18-59 years who were treated with chemotherapy only without upfront hematopoietic cell transplant (HCT), younger age, female, CBF AML, higher income, and private insurance conferred higher 10-year OS. Among patients, 18-59 years treated with chemotherapy and upfront HCT, younger age and private insurance conferred higher 10-year OS. In a Cox proportional hazard model, the likelihood of death decreased with younger age, fewer comorbidities, treatment at an academic center, private insurance, and use of multiagent chemotherapy. Our results demonstrate poor long-term OS even among younger patients and highlights disparities in leukemia care based on insurance type.

A precision medicine approach to management of acute myeloid leukemia in older adults.

PURPOSE OF REVIEW: Therapy selection in older adults with acute myeloid leukemia (AML) can be challenging because of a higher incidence of high-risk cytogenetic and molecular features conferring chemoresistance and poor functional status leading to increased treatment-related toxicities. The purpose of this review is to highlight the recent advances in precision medicine in AML that have shown promise to improve outcomes of older adults. RECENT FINDINGS: The utilization of next generation sequencing to identify and target actionable mutations can influence therapy selection in one-third of patients and can result in higher response rates as well as survival compared with those who do not receive targeted therapy. Oral targeted agents are available for AML with IDH 1, IDH2, or FLT3 mutations. Low-intensity venetoclax-based regimens have shown high rates of responses in AML, particularly among those with NPM1 and IDH2 mutations; responses are often durable and associated with minimal residual disease (MRD) negativity. Multiple studies have demonstrated the prognostic significance of flow cytometric MRD, with potential implications for subsequent therapy. SUMMARY: Novel approaches for AML risk-stratification, MRD assessment, and a precision medicine approach offer significant promise to improve survival and quality of life of older adults.

Novel Treatment Paradigms in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease marked by the presence of several driver mutations and molecular subgroups even in a single patient. The genetic and molecular heterogeneity is also reflected by a progressive shift from a morphologic classification to one informed by causative genomic changes. Cytogenetic results and somatic mutations are increasingly being utilized to guide use of intensive chemotherapy and low-intensity chemotherapy, particularly among older adults. Utilization of next-generation sequencing in AML has led to increasing use of targeted treatments for actionable mutations. Quantitative real-time polymerase chain reaction-based mutational analysis and multicolor flow cytometry offer sensitive assays that can detect minimal residual disease (MRD). Several studies have shown that MRD negativity, as defined by specified cutoff values, is highly prognostic with potential therapeutic implications. The last 3 years mark an unprecedented history in the drug development in AML with approval of 8 new drugs and large portfolio of ongoing early and late-phase trials of several promising drugs. Multiple combinatorial trials of approved agents and approval of newer agents in the future will continue to change the therapeutic landscape of AML.