CA: A Cancer Journal for Clinicians

The first 5 decades of research in acute myeloid leukemia (AML) were dominated by the cytarabine plus anthracyclines backbone, with advances in strategies including allogeneic hematopoietic stem cell transplantation, high‐dose cytarabine, supportive care measures, and targeted therapies for the subset of patients with acute promyelocytic leukemia. Since 2017, a turning point in AML research, 12 agents have received regulatory approval for AML in the United States: venetoclax (BCL2 inhibitor); gemtuzumab ozogamicin (CD33 antibody–drug conjugate); midostaurin, gilteritinib, and quizartinib (fms‐like tyrosine kinase 3 inhibitors); ivosidenib, olutasidenib, and enasidenib (isocitrate dehydrogenase 1 and 2 inhibitors); oral azacitidine (a partially absorbable formulation); CPX351 (liposomal encapsulation of cytarabine:daunorubicin at a molar ratio of 5:1); glasdegib (hedgehog inhibitor); and recently revumenib (menin inhibitor; approved November 2024). Oral decitabine‐cedazuridine, which is approved as a bioequivalent alternative to parenteral hypomethylating agents in myelodysplastic syndrome, can be used for the same purpose in AML. Menin inhibitors, CD123 antibody–drug conjugates, and other antibodies targeting CD123, CD33, and other surface markers are showing promising results. Herein, the authors review the frontline and later line therapies in AML and discuss important research directions.

In the United States, over 2 million individuals openly identify with a gender that differs from their sex assigned at birth. A cancer diagnosis is physically and psychologically taxing—and, in some, traumatic. However, for transgender and gender‐diverse (TGD) people, many of whom have experienced discrimination in myriad health care settings, the challenges may be even greater. These recommendations focus on how best to deliver quality cancer care to transgender men (individuals who identify as men but were assigned female sex at birth), transgender women (individuals who identify as women but were assigned male sex at birth), and people who identify somewhere beyond this gender spectrum as nonbinary or using other terms, based on the available, albeit sparse, literature. This review broaches: (1) the epidemiology of cancer in TGD individuals, including the incidence of cancer and cancer‐related mortality; (2) cancer center practices that are welcoming and affirming to TGD patients; (3) the need for awareness and intentionality in the spaces of diagnosis and treatment for cancer; (4) the inevitable conclusion that gender differences exist but much more needs to be learned about the impact of gender‐affirming therapy, consisting of gender‐affirming surgeries and gender‐affirming hormone therapy, on cancer therapy; and (5) the efficacy and perceived safety of antineoplastic therapy and gender‐affirming hormone therapy.

This is the American Cancer Society's biennial update of statistics on breast cancer among women based on high‐quality incidence and mortality data from the National Cancer Institute and the Centers for Disease Control and Prevention. Breast cancer incidence continued an upward trend, rising by 1% annually during 2012–2021, largely confined to localized‐stage and hormone receptor‐positive disease. A steeper increase in women younger than 50 years (1.4% annually) versus 50 years and older (0.7%) overall was only significant among White women. Asian American/Pacific Islander women had the fastest increase in both age groups (2.7% and 2.5% per year, respectively); consequently, young Asian American/Pacific Islander women had the second lowest rate in 2000 (57.4 per 100,000) but the highest rate in 2021 (86.3 per 100,000) alongside White women (86.4 per 100,000), surpassing Black women (81.5 per 100,000). In contrast, the overall breast cancer death rate continuously declined during 1989–2022 by 44% overall, translating to 517,900 fewer breast cancer deaths during this time. However, not all women have experienced this progress; mortality remained unchanged since 1990 in American Indian/Alaska Native women, and Black women have 38% higher mortality than White women despite 5% lower incidence. Although the Black‐White disparity partly reflects more triple‐negative cancers, Black women have the lowest survival for every breast cancer subtype and stage except localized disease, with which they are 10% less likely to be diagnosed than White women (58% vs. 68%), highlighting disadvantages in social determinants of health. Progress against breast cancer could be accelerated by mitigating racial, ethnic, and social disparities through improved clinical trial representation and access to high‐quality screening and treatment.

Older adults with cancer heterogeneously experience health care, treatment, and symptoms. Geriatric assessment (GA) offers a comprehensive evaluation of an older individual's health status and can predict cancer‐related outcomes in individuals with solid tumors and those with hematologic malignancies. In the last decade, randomized controlled trials have demonstrated the benefits of GA and GA management (GAM), which uses GA information to provide tailored intervention strategies to address GA impairments (e.g., implementing physical therapy for impaired physical function). Multiple phase 3 clinical trials in older adults with solid tumors and hematologic malignancies have demonstrated that GAM improves treatment completion, quality of life, communication, and advance care planning while reducing treatment‐related toxicity, falls, and polypharmacy. Nonetheless, implementation and uptake of GAM remain challenging. Various strategies have been proposed, including the use of GA screening tools, to identify patients most likely to benefit from GAM, the systematic engagement of the oncology workforce in the delivery of GAM, and the integration of technologies like telemedicine and mobile health to enhance the availability of GA and GAM interventions. Health inequities in minoritized groups persist, and systematic GA implementation has the potential to capture social determinants of health that are relevant to equitable care. Caregivers play an important role in cancer care and experience burden themselves. GA can guide dyadic supportive care interventions, ultimately helping both patients and caregivers achieve optimal health.

In 2018, the authors reported estimates of the number and proportion of cancers attributable to potentially modifiable risk factors in 2014 in the United States. These data are useful for advocating for and informing cancer prevention and control. Herein, based on up‐to‐date relative risk and cancer occurrence data, the authors estimated the proportion and number of invasive cancer cases (excluding nonmelanoma skin cancers) and deaths, overall and for 30 cancer types among adults who were aged 30 years and older in 2019 in the United States, that were attributable to potentially modifiable risk factors. These included cigarette smoking; second‐hand smoke; excess body weight; alcohol consumption; consumption of red and processed meat; low consumption of fruits and vegetables, dietary fiber, and dietary calcium; physical inactivity; ultraviolet radiation; and seven carcinogenic infections. Numbers of cancer cases and deaths were obtained from data sources with complete national coverage, risk factor prevalence estimates from nationally representative surveys, and associated relative risks of cancer from published large‐scale pooled or meta‐analyses. In 2019, an estimated 40.0% (713,340 of 1,781,649) of all incident cancers (excluding nonmelanoma skin cancers) and 44.0% (262,120 of 595,737) of all cancer deaths in adults aged 30 years and older in the United States were attributable to the evaluated risk factors. Cigarette smoking was the leading risk factor contributing to cancer cases and deaths overall (19.3% and 28.5%, respectively), followed by excess body weight (7.6% and 7.3%, respectively), and alcohol consumption (5.4% and 4.1%, respectively). For 19 of 30 evaluated cancer types, more than one half of the cancer cases and deaths were attributable to the potentially modifiable risk factors considered in this study. Lung cancer had the highest number of cancer cases (201,660) and deaths (122,740) attributable to evaluated risk factors, followed by female breast cancer (83,840 cases), skin melanoma (82,710), and colorectal cancer (78,440) for attributable cases and by colorectal (25,800 deaths), liver (14,720), and esophageal (13,600) cancer for attributable deaths. Large numbers of cancer cases and deaths in the United States are attributable to potentially modifiable risk factors, underscoring the potential to substantially reduce the cancer burden through broad and equitable implementation of preventive initiatives.

Social media is widely used globally by patients, families of patients, health professionals, scientists, and other stakeholders who seek and share information related to cancer. Despite many benefits of social media for cancer care and research, there is also a substantial risk of exposure to misinformation, or inaccurate information about cancer. Types of misinformation vary from inaccurate information about cancer risk factors or unproven treatment options to conspiracy theories and public relations articles or advertisements appearing as reliable medical content. Many characteristics of social media networks—such as their extensive use and the relative ease it allows to share information quickly—facilitate the spread of misinformation. Research shows that inaccurate and misleading health‐related posts on social media often get more views and engagement (e.g., likes, shares) from users compared with accurate information. Exposure to misinformation can have downstream implications for health‐related attitudes and behaviors. However, combatting misinformation is a complex process that requires engagement from media platforms, scientific and health experts, governmental organizations, and the general public. Cancer experts, for example, should actively combat misinformation in real time and should disseminate evidence‐based content on social media. Health professionals should give information prescriptions to patients and families and support health literacy. Patients and families should vet the quality of cancer information before acting upon it (e.g., by using publicly available checklists) and seek recommended resources from health care providers and trusted organizations. Future multidisciplinary research is needed to identify optimal ways of building resilience and combating misinformation across social media.

Tumor‐agnostic therapies represent a paradigm shift in oncology by altering the traditional means of characterizing tumors based on their origin or location. Instead, they zero in on specific genetic anomalies responsible for fueling malignant growth. The watershed moment for tumor‐agnostic therapies arrived in 2017, with the US Food and Drug Administration's historic approval of pembrolizumab, an immune checkpoint inhibitor. This milestone marked the marriage of genomics and immunology fields, as an immunotherapeutic agent gained approval based on genomic biomarkers, specifically, microsatellite instability‐high or mismatch repair deficiency (dMMR). Subsequently, the approval of NTRK inhibitors, designed to combat NTRK gene fusions prevalent in various tumor types, including pediatric cancers and adult solid tumors, further underscored the potential of tumor‐agnostic therapies. The US Food and Drug Administration approvals of targeted therapies (BRAF V600E, RET fusion), immunotherapies (tumor mutational burden ≥10 mutations per megabase, dMMR) and an antibody‐drug conjugate (Her2‐positive–immunohistochemistry 3+ expression) with pan‐cancer efficacy have continued, offering newfound hope to patients grappling with advanced solid tumors that harbor particular biomarkers. In this comprehensive review, the authors delve into the expansive landscape of tissue‐agnostic targets and drugs, shedding light on the rationale underpinning this approach, the hurdles it faces, presently approved therapies, voices from the patient advocacy perspective, and the tantalizing prospects on the horizon. This is a welcome advance in oncology that transcends the boundaries of histology and location to provide personalized options.

Cancer mortality rates have declined during the last 28 years, but that process is not equitably shared. Disparities in cancer outcomes by race, ethnicity, socioeconomic status, sexual orientation and gender identity, and geographic location persist across the cancer care continuum. Consequently, community outreach and engagement (COE) efforts within National Cancer Institute‐Designated Cancer Center (NCI‐DCC) catchment areas have intensified during the last 10 years as has the emphasis on COE and catchment areas in NCI's Cancer Center Support Grant applications. This review article attempts to provide a historic perspective of COE within NCI‐DCCs. Improving COE has long been an important initiative for the NCI, but it was not until 2012 and 2016 that NCI‐DCCs were required to define their catchment areas rigorously and to provide specific descriptions of COE interventions, respectively. NCI‐DCCs had previously lacked adequate focus on the inclusion of historically marginalized patients in cancer innovation efforts. Integrating COE efforts throughout the research and operational aspects of the cancer centers, at both the patient and community levels, will expand the footprint of COE efforts within NCI‐DCCs. Achieving this change requires sustained commitment by the centers to adjust their activities and improve access and outcomes for historically marginalized communities.

The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including gastroenteropancreatic neuroendocrine tumors (GEP‐NETs), is meant to be dynamic, requiring periodic updates to optimize AJCC staging definitions. This entails the collaboration of experts charged with evaluating new evidence that supports changes to each staging system. GEP‐NETs are the second most prevalent neoplasm of gastrointestinal origin after colorectal cancer. Since publication of the AJCC eighth edition, the World Health Organization has updated the classification and separates grade 3 GEP‐NETs from poorly differentiated neuroendocrine carcinoma. In addition, because of major advancements in diagnostic and therapeutic technologies for GEP‐NETs, AJCC version 9 advocates against the use of serum chromogranin A for the diagnosis and monitoring of GEP‐NETs. Furthermore, AJCC version 9 recognizes the increasing role of endoscopy and endoscopic resection in the diagnosis and management of NETs, particularly in the stomach, duodenum, and colorectum. Finally, T1NXM0 has been added to stage I in these disease sites as well as in the appendix.

The rising costs of cancer care and subsequent medical financial hardship for cancer survivors and families are well documented in the United States. Less attention has been paid to employment disruptions and loss of household income after a cancer diagnosis and during treatment, potentially resulting in lasting financial hardship, particularly for working‐age adults not yet age‐eligible for Medicare coverage and their families. In this article, the authors use a composite patient case to illustrate the adverse consequences of cancer diagnosis and treatment for employment, health insurance coverage, household income, and other aspects of financial hardship. They summarize existing research and provide nationally representative estimates of multiple aspects of financial hardship and health insurance coverage, benefit design, and employee benefits, such as paid sick leave, among working‐age adults with a history of cancer and compare them with estimates among working‐age adults without a history of cancer from the most recently available years of the National Health Interview Survey (2019–2021). Then, the authors identify opportunities for addressing employment and health insurance coverage challenges at multiple levels, including federal, state, and local policies; employers; cancer care delivery organizations; and nonprofit organizations. These efforts, when informed by research to identify best practices, can potentially help mitigate the financial hardship associated with cancer.

This article presents global cancer statistics by world region for the year 2022 based on updated estimates from the International Agency for Research on Cancer (IARC). There were close to 20 million new cases of cancer in the year 2022 (including nonmelanoma skin cancers [NMSCs]) alongside 9.7 million deaths from cancer (including NMSC). The estimates suggest that approximately one in five men or women develop cancer in a lifetime, whereas around one in nine men and one in 12 women die from it. Lung cancer was the most frequently diagnosed cancer in 2022, responsible for almost 2.5 million new cases, or one in eight cancers worldwide (12.4% of all cancers globally), followed by cancers of the female breast (11.6%), colorectum (9.6%), prostate (7.3%), and stomach (4.9%). Lung cancer was also the leading cause of cancer death, with an estimated 1.8 million deaths (18.7%), followed by colorectal (9.3%), liver (7.8%), female breast (6.9%), and stomach (6.8%) cancers. Breast cancer and lung cancer were the most frequent cancers in women and men, respectively (both cases and deaths). Incidence rates (including NMSC) varied from four‐fold to five‐fold across world regions, from over 500 in Australia/New Zealand (507.9 per 100,000) to under 100 in Western Africa (97.1 per 100,000) among men, and from over 400 in Australia/New Zealand (410.5 per 100,000) to close to 100 in South‐Central Asia (103.3 per 100,000) among women. The authors examine the geographic variability across 20 world regions for the 10 leading cancer types, discussing recent trends, the underlying determinants, and the prospects for global cancer prevention and control. With demographics‐based predictions indicating that the number of new cases of cancer will reach 35 million by 2050, investments in prevention, including the targeting of key risk factors for cancer (including smoking, overweight and obesity, and infection), could avert millions of future cancer diagnoses and save many lives worldwide, bringing huge economic as well as societal dividends to countries over the forthcoming decades.