CA Cancer J Clin
· 2025 · PMID 40146038
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Individuals from rural areas in the United States suffer higher rates of morbidity and mortality from cancer than their urban counterparts. This review is based on the idea that equity-the elimination of unnecessary and...Individuals from rural areas in the United States suffer higher rates of morbidity and mortality from cancer than their urban counterparts. This review is based on the idea that equity-the elimination of unnecessary and preventable differences between groups of individuals-should underlie access to cancer care resources for patients from rural areas. Access to cancer clinical trials serves as the framework for identifying and understanding barriers in access to quality oncologic care. The authors discuss the interplay between rural living, socioeconomic status, culture, and health; and they highlight how economic considerations in rural areas often limit access to clinical trials and oncologic care because economies of scale do not apply in these regions given the requirement for high-quality oncology care even with lower patient volumes. The authors propose solutions to enhance access to clinical trials and improve the quality of oncologic care in rural areas, viewing these aims as ethical and moral imperatives.
Islami F, Nargis N, Liu Q
… +6 more, Bandi P, Siegel RL, Choudhury PP, Freedman ND, Warner KE, Jemal A
CA Cancer J Clin
· 2025 · PMID 40131130
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Lung cancer mortality rates in the United States have declined steeply in recent decades, largely because of substantial reductions in smoking prevalence, as approximately 85% of lung cancer deaths are attributable to ci...Lung cancer mortality rates in the United States have declined steeply in recent decades, largely because of substantial reductions in smoking prevalence, as approximately 85% of lung cancer deaths are attributable to cigarette smoking. In this study, the authors estimate the number of averted lung cancer deaths and corresponding person-years of life gained during 1970-2022 as a measure of progress in cancer prevention through tobacco control. By using the 1970-2022 National Center for Health Statistics mortality data (with national coverage), the authors calculated the expected number of deaths for each year, age, sex, race, and age group based on the expected lung cancer death rate multiplied by the population at risk in that group. The number of averted lung cancer deaths were calculated by subtracting the observed number of deaths from the expected number in each group. Person-years of life gained were estimated as a measure of avoided premature mortality based on the average additional years a person would have lived if they had not died from lung cancer. The authors estimated that 3,856,240 lung cancer deaths (2,246,610 in men, 1,609,630 in women) were averted, and 76,275,550 person-years of life (40,277,690 in men, 35,997,860 in women) were gained during 1970-2022, with an average of 19.8 person-years of life gained (17.9 in men, 22.4 in women) per averted death. The number of averted lung cancer deaths accounted for 51.4% of the estimated declines in overall cancer deaths and was substantially greater in men (60.1%) than in women (42.7%). By race, this proportion was 53.6% in the White population (62.8% in men, 44.6% in women) and 40.0% in the Black population (44.4% in men, 34.7% in women). The substantial estimated numbers of averted lung cancer deaths and person-years of life gained highlight the remarkable effect of progress against smoking on reducing premature mortality from lung cancer.
CA Cancer J Clin
· 2025 · PMID 40057846
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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...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.
Saka AH, Giaquinto AN, McCullough LE
… +4 more, Tossas KY, Star J, Jemal A, Siegel RL
CA Cancer J Clin
· 2025 · PMID 39976243
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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 year...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.
Tang LL, Chen L, Xu GQ
… +20 more, Zhang N, Huang CL, Li WF, Mao YP, Zhou GQ, Lei F, Chen LS, Huang SH, Chen L, Chen YP, Zhang Y, Liu X, Xu C, Zhao Y, Li JB, Liu N, Xie FY, Guo R, Sun Y, Ma J
CA Cancer J Clin
· 2025 · PMID 39970442
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BACKGROUND: Nearly 90% locoregionally advanced nasopharyngeal carcinoma (LANPC) responds to induction chemotherapy (IC) with significant tumor volume shrinkage. Radiotherapy always follows IC, and reduced volume has been...BACKGROUND: Nearly 90% locoregionally advanced nasopharyngeal carcinoma (LANPC) responds to induction chemotherapy (IC) with significant tumor volume shrinkage. Radiotherapy always follows IC, and reduced volume has been proposed. However, the efficacy and safety of reduced-volume radiotherapy is uncertain. METHODS: In this multi-center, noninferiority, randomized, controlled trial, patients with LANPC who completed IC were randomly assigned (1:1) to receive reduced-volume radiotherapy based on post-IC tumor volume (Post-IC group) or conventional volume radiotherapy based on pre-IC tumor volume (Pre-IC group). The primary endpoint was locoregional relapse-free survival, with a noninferiority margin of 8%. Secondary endpoints comprised adverse events, and quality of life (QoL). RESULTS: Between August 7, 2020, and May 27, 2022, 445 patients were randomly assigned to Post-IC (n = 225) or Pre-IC (n = 220) groups. The average volume receiving radical dose was 66.6 cm in Post-IC group versus 80.9 cm. After a median follow-up of 40.4 months, the 3-year locoregional relapse-free survival was 91.5% in the Post-IC group versus 91.2%, with a difference of 0.3% (95% confidence interval -4.9% to 5.5%). The incidence of grade 3-4 radiation-related toxicity was lower in the Post-IC group including: acute mucositis (19.8% vs 34.1%), late otitis media (9.5% vs 20.9%) and late dry month (3.6% vs 9.5%). The Post-IC group had better QoL for global health status, physical functioning, emotional functioning, dry mouth and sticky saliva. CONCLUSIONS: In this trial, reduced-volume radiotherapy was noninferior to conventional volume radiotherapy in locoregional relapse-free survival, and was associated with lower toxicities and improved QoL. (ClinicalTrials.gov identifier NCT04384627).
Nikanjam M, Kato S, Allen T
… +2 more, Sicklick JK, Kurzrock R
CA Cancer J Clin
· 2025 · PMID 39841128
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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 t...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 × 10 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.
Siegel RL, Kratzer TB, Giaquinto AN
… +2 more, Sung H, Jemal A
CA Cancer J Clin
· 2025 · PMID 39817679
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Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes using incidence data c...Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes using incidence data collected by central cancer registries (through 2021) and mortality data collected by the National Center for Health Statistics (through 2022). In 2025, 2,041,910 new cancer cases and 618,120 cancer deaths are projected to occur in the United States. The cancer mortality rate continued to decline through 2022, averting nearly 4.5 million deaths since 1991 because of smoking reductions, earlier detection for some cancers, and improved treatment. Yet alarming disparities persist; Native American people bear the highest cancer mortality, including rates that are two to three times those in White people for kidney, liver, stomach, and cervical cancers. Similarly, Black people have two-fold higher mortality than White people for prostate, stomach, and uterine corpus cancers. Overall cancer incidence has generally declined in men but has risen in women, narrowing the male-to-female rate ratio (RR) from a peak of 1.6 (95% confidence interval, 1.57-1.61) in 1992 to 1.1 (95% confidence interval, 1.12-1.12) in 2021. However, rates in women aged 50-64 years have already surpassed those in men (832.5 vs. 830.6 per 100,000), and younger women (younger than 50 years) have an 82% higher incidence rate than their male counterparts (141.1 vs. 77.4 per 100,000), up from 51% in 2002. Notably, lung cancer incidence in women surpassed that in men among people younger than 65 years in 2021 (15.7 vs. 15.4 per 100,000; RR, 0.98, p = 0.03). In summary, cancer mortality continues to decline, but future gains are threatened by rampant racial inequalities and a growing burden of disease in middle-aged and young adults, especially women. Continued progress will require investment in cancer prevention and access to equitable treatment, especially for Native American and Black individuals.
Hage Chehade C, Gebrael G, Sayegh N
… +8 more, Ozay ZI, Narang A, Crispino T, Golan T, Litton JK, Swami U, Moore KN, Agarwal N
CA Cancer J Clin
· 2025 · PMID 39791278
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Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors, such as olaparib, talazoparib, rucaparib, and niraparib, comprise a therapeutic class that targets PARP proteins involved in DNA repair. Cancer cells with...Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors, such as olaparib, talazoparib, rucaparib, and niraparib, comprise a therapeutic class that targets PARP proteins involved in DNA repair. Cancer cells with homologous recombination repair defects, particularly BRCA alterations, display enhanced sensitivity to these agents because of synthetic lethality induced by PARP inhibitors. These agents have significantly improved survival outcomes across various malignancies, initially gaining regulatory approval in ovarian cancer and subsequently in breast, pancreatic, and prostate cancers in different indications. This review offers a comprehensive clinical overview of PARP inhibitor approvals, emphasizing their efficacy across different cancers based on landmark phase 3 clinical trials.
Gencel-Augusto J, Minaya NJ, Johnson DE
… +1 more, Grandis JR
CA Cancer J Clin
· 2025 · PMID 39785094
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Despite ongoing efforts to increase the number of women in science, technology, engineering, and mathematics (STEM) and in medicine, Hispanic women remain severely underrepresented in these fields. This disparity not onl...Despite ongoing efforts to increase the number of women in science, technology, engineering, and mathematics (STEM) and in medicine, Hispanic women remain severely underrepresented in these fields. This disparity not only hinders scientific innovation and the delivery of culturally competent medical care but also perpetuates a systemic exclusion. Research specifically addressing the challenges faced by Hispanic women, the extent of underrepresentation in these disciplines, and strategies to mitigate these issues is sparce. The authors conducted a systematic analysis of peer-reviewed articles to address this gap. The findings reveal a stark underrepresentation of Hispanic women across all examined fields, particularly compared with White women. In addition, the underrepresentation persists when compared with Hispanic men, although the disparity is less pronounced. The authors identify ongoing disparities in promotion, compensation, and retention rates for Hispanic women; present data for barriers to entry and retention; and highlight existing programs and strategies aimed at addressing this underrepresentation. Finally, a framework is presented for future studies and actionable initiatives, and the broader implications of these findings for the field of oncology are highlighted.
Kantarjian HM, DiNardo CD, Kadia TM
… +7 more, Daver NG, Altman JK, Stein EM, Jabbour E, Schiffer CA, Lang A, Ravandi F
CA Cancer J Clin
· 2025 · PMID 39656142
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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, hig...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.
Cathcart-Rake EJ, Chan A, Menendez A
… +4 more, Markstrom D, Schnitzlein C, Chong YW, Dizon DS
CA Cancer J Clin
· 2025 · PMID 39652385
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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,...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.