CA: A Cancer Journal for Clinicians最新文献

When Patricia Santos, MD, was a medical resident in radiation oncology at Memorial Sloan Kettering Cancer Center (MSKCC) in New York, she and her colleagues observed the numerous challenges that people experiencing homelessness (PEH) face after a cancer diagnosis.

“A number of us who were doing work in this space had our own individual stories of what we saw on a one-on-one basis, but we found very little literature on what that actually meant for cancer care delivery and services among the unhoused,” says Dr Santos, now an assistant professor of radiation oncology at Emory University School of Medicine in Atlanta, Georgia.

She practices at Atlanta’s Grady Memorial Hospital, one of the largest public safety net hospitals in the country.

Setting out to learn more while still at MSKCC, she and her colleagues launched a study that was published in JAMA Oncology (doi:10.1001/jamaoncol.2024.3645). This large cross-sectional study of hospitalized US adults diagnosed with cancer found that PEH had higher prevalences of lung and upper gastrointestinal cancers along with comorbid substance use disorder and HIV. Despite these diagnoses and longer hospital stays, these individuals were less likely to undergo invasive procedures or systemic therapy or have higher-than-median costs of stay than housed populations. Homelessness was associated with a lower rate of death while a patient was in the hospital. However, PEH were found to be 4 times more likely to be discharged against medical advice.

Using the 2016–2020 National Inpatient Sample, the cross-sectional study assessed hospitalized inpatient adults aged 18 years or older who were diagnosed with cancer. Researchers developed a cohort of PEH and housed individuals who were matched according to age, sex, race, ethnicity, insurance type, cancer diagnosis, number of comorbidities, substance abuse disorder, severity of illness, year of admission, hospital location, hospital ownership, region, and hospital bed size.

The study included 13,793,462 housed individuals (median age, 68 years) and 45,150 PEH (median age, 58 years).

Despite the advances in cancer prevention, early detection, and treatments, all of which have led to improved cancer survival, globally, there is an increased incidence in cancer-related deaths. Although each patient and each tumor is wholly unique, the tipping point to incurable disease is common across all patients: the dual capacity for cancers to metastasize and resist systemic treatment. The discovery of genetic mutations and epigenetic variation that emerges during cancer progression highlights that evolutionary and ecology principles can be used to understand how cancer evolves to a lethal phenotype. By applying such an eco-evolutionary framework, the authors reinterpret our understanding of the metastatic process as one of an ecologic invasion and define the eco-evolutionary paths of evolving therapy resistance. With this understanding, the authors draw from successful strategies optimized in evolutionary ecology to define strategic interventions with the goal of altering the evolutionary trajectory of lethal cancer. Ultimately, studying, understanding, and treating cancer using evolutionary ecology principles provides an opportunity to improve the lives of patients with cancer.

African American and other Black individuals (referred to as Black people in this article) have a disproportionate cancer burden, including the lowest survival of any racial or ethnic group for most cancers. Every 3 years, the American Cancer Society estimates the number of new cancer cases and deaths for Black people in the United States and compiles the most recent data on cancer incidence (herein through 2021), mortality (through 2022), survival, screening, and risk factors using population-based data from the National Cancer Institute and the Centers for Disease Control and Prevention. In 2025, there will be approximately 248,470 new cancer cases and 73,240 cancer deaths among Black people in the United States. Black men have experienced the largest relative decline in cancer mortality from 1991 to 2022 overall (49%) and in almost every 10-year age group, by as much as 65%–67% in the group aged 40–59 years. This progress largely reflects historical reductions in smoking initiation among Black teens, advances in treatment, and earlier detections for some cancers. Nevertheless, during the most recent 5 years, Black men had 16% higher mortality than White men despite just 4% higher incidence, and Black women had 10% higher mortality than White women despite 9% lower incidence. Larger inequalities for mortality than for incidence reflect two-fold higher death rates for prostate, uterine corpus, and stomach cancers and for myeloma, and 40%–50% higher rates for colorectal, breast, cervical, and liver cancers. The causes of ongoing disparities are multifactorial, but largely stem from inequalities in the social determinants of health that trace back to structural racism. Increasing diversity in clinical trials, enhancing provider education, and implementing financial incentives to ensure equitable care across the cancer care continuum would help close these gaps.

Next-generation sequencing has revealed the disruptive reality that advanced/metastatic cancers have complex and individually distinct genomic landscapes, necessitating a rethinking of treatment strategies and clinical trial designs. Indeed, the molecular reclassification of cancer suggests that it is the molecular underpinnings of the disease, rather than the tissue of origin, that mostly drives outcomes. Consequently, oncology clinical trials have evolved from standard phase 1, 2, and 3 tissue-specific studies; to tissue-specific, biomarker-driven trials; to tissue-agnostic trials untethered from histology (all drug-centered designs); and, ultimately, to patient-centered, N-of-1 precision medicine studies in which each patient receives a personalized, biomarker-matched therapy/combination of drugs. Innovative technologies beyond genomics, including those that address transcriptomics, immunomics, proteomics, functional impact, epigenetic changes, and metabolomics, are enabling further refinement and customization of therapy. Decentralized studies have the potential to improve access to trials and precision medicine approaches for underserved minorities. Evaluation of real-world data, assessment of patient-reported outcomes, use of registry protocols, interrogation of exceptional responders, and exploitation of synthetic arms have all contributed to personalized therapeutic approaches. With greater than 1 × 10¹² potential patterns of genomic alterations and greater than 4.5 million possible three-drug combinations, the deployment of artificial intelligence/machine learning may be necessary for the optimization of individual therapy and, in the near future, also may permit the discovery of new treatments in real time.