CA: A Cancer Journal for Clinicians最新文献

The 2024 update to Cancer Statistics from the American Cancer Society estimates that over 2,000,000 people this year will hear the words, “you have cancer.”¹ This amounts to nearly 5500 people each day, or the equivalent to one person experiencing this every 15 seconds. This marks the first time incidence has eclipsed 2 million Americans, with more people being diagnosed at earlier stages of these diseases, when cure rates are the highest. Consequently, cancer mortality continues to decline, with an estimated 4.1 million lives saved since 1991, because of significant investments in research and screening by the National Institutes of Health, the Centers for Disease Control and Prevention, the American Cancer Society, and others. To us, four parts of the report particularly stand out.

First, historically, cancer has been a disease that disproportionally affects men. However, this report demonstrates that, whereas the cancer incidence in men has been stable since the 2013, the incidence in women has ticked up since the late 1990s, attributed to higher rates of breast and uterine corpus cancers and melanoma. Thus cancer is becoming more gender-indiscriminate, with a male-to-female incidence ratio of 1.14 (95% CI, 1.136–1.143) in all ages. Many have hypothesized that differential lifestyle and risk-taking behaviors, alongside environmental exposures, resulted in higher cancer rates in men. However, as the incidence gap between genders closes, signs may point to risk factors (e.g., obesity, sedentary lifestyle) that are similarly affecting both groups, highlighting the need for a better understanding of this phenomenon.

Second, although the overall cancer incidence is increasing, there are particular cancers and populations disproportionately affected. For example, whereas the rise in uterine corpus cancers in White women has increased by about 1% per year since the mid-2000s, the increase is in excess of 2% in Black, Hispanic, Asian American, and Pacific Islander people. Colorectal cancer (CRC) too shows a variability when age is considered; the declines noted in CRC are largely because of a lower rate in people older than 65 years; among those younger than 55 years, the rate continues to increase by 1% to 2% per year. Finally, men saw their rates stabilize for liver cancer and, potentially, for melanoma between 2015 and 2019, yet women saw their rates increase by 2% per year. Taken together, the report highlights how cancer cannot be over-simplified to one diagnosis, nor can we generalize these trends in a short bullet.

Third, although the report highlights the tremendous advances in the treatment of hematologic and advanced solid tumor malignancies, the impact of disparities cannot be overstated. Compared with White women, for example, more Black women are diagnosed at a more advanced stage (44% vs. 23%) and have a poorer prognosis (5-year survival rate estimates of 63% vs. 84%, respectively). As the aut

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 2020) and mortality data collected by the National Center for Health Statistics (through 2021). In 2024, 2,001,140 new cancer cases and 611,720 cancer deaths are projected to occur in the United States. Cancer mortality continued to decline through 2021, averting over 4 million deaths since 1991 because of reductions in smoking, earlier detection for some cancers, and improved treatment options in both the adjuvant and metastatic settings. However, these gains are threatened by increasing incidence for 6 of the top 10 cancers. Incidence rates increased during 2015–2019 by 0.6%–1% annually for breast, pancreas, and uterine corpus cancers and by 2%–3% annually for prostate, liver (female), kidney, and human papillomavirus-associated oral cancers and for melanoma. Incidence rates also increased by 1%–2% annually for cervical (ages 30–44 years) and colorectal cancers (ages <55 years) in young adults. Colorectal cancer was the fourth-leading cause of cancer death in both men and women younger than 50 years in the late-1990s but is now first in men and second in women. Progress is also hampered by wide persistent cancer disparities; compared to White people, mortality rates are two-fold higher for prostate, stomach and uterine corpus cancers in Black people and for liver, stomach, and kidney cancers in Native American people. Continued national progress will require increased investment in cancer prevention and access to equitable treatment, especially among American Indian and Alaska Native and Black individuals.

The last decade has seen rapid progress in the use of genomic tests, including gene panels, whole-exome sequencing, and whole-genome sequencing, in research and clinical cancer care. These advances have created expansive opportunities to characterize the molecular attributes of cancer, revealing a subset of cancer-associated aberrations called driver mutations. The identification of these driver mutations can unearth vulnerabilities of cancer cells to targeted therapeutics, which has led to the development and approval of novel diagnostics and personalized interventions in various malignancies. The applications of this modern approach, often referred to as precision oncology or precision cancer medicine, are already becoming a staple in cancer care and will expand exponentially over the coming years. Although genomic tests can lead to better outcomes by informing cancer risk, prognosis, and therapeutic selection, they remain underutilized in routine cancer care. A contributing factor is a lack of understanding of their clinical utility and the difficulty of results interpretation by the broad oncology community. Practical guidelines on how to interpret and integrate genomic information in the clinical setting, addressed to clinicians without expertise in cancer genomics, are currently limited. Building upon the genomic foundations of cancer and the concept of precision oncology, the authors have developed practical guidance to aid the interpretation of genomic test results that help inform clinical decision making for patients with cancer. They also discuss the challenges that prevent the wider implementation of precision oncology.

Pain is one of the most burdensome symptoms in people with cancer, and opioid analgesics are considered the mainstay of cancer pain management. For this review, the authors evaluated the efficacy and toxicities of opioid analgesics compared with placebo, other opioids, nonopioid analgesics, and nonpharmacologic treatments for background cancer pain (continuous and relatively constant pain present at rest), and breakthrough cancer pain (transient exacerbation of pain despite stable and adequately controlled background pain). They found a paucity of placebo-controlled trials for background cancer pain, although tapentadol or codeine may be more efficacious than placebo (moderate-certainty to low-certainty evidence). Nonsteroidal anti-inflammatory drugs including aspirin, piroxicam, diclofenac, ketorolac, and the antidepressant medicine imipramine, may be at least as efficacious as opioids for moderate-to-severe background cancer pain. For breakthrough cancer pain, oral transmucosal, buccal, sublingual, or intranasal fentanyl preparations were identified as more efficacious than placebo but were more commonly associated with toxicities, including constipation and nausea. Despite being recommended worldwide for the treatment of cancer pain, morphine was generally not superior to other opioids, nor did it have a more favorable toxicity profile. The interpretation of study results, however, was complicated by the heterogeneity in the study populations evaluated. Given the limited quality and quantity of research, there is a need to reappraise the clinical utility of opioids in people with cancer pain, particularly those who are not at the end of life, and to further explore the effects of opioids on immune system function and quality of life in these individuals.

In 2021, the American Cancer Society published its first biennial report on the status of cancer disparities in the United States. In this second report, the authors provide updated data on racial, ethnic, socioeconomic (educational attainment as a marker), and geographic (metropolitan status) disparities in cancer occurrence and outcomes and contributing factors to these disparities in the country. The authors also review programs that have reduced cancer disparities and provide policy recommendations to further mitigate these inequalities. There are substantial variations in risk factors, stage at diagnosis, receipt of care, survival, and mortality for many cancers by race/ethnicity, educational attainment, and metropolitan status. During 2016 through 2020, Black and American Indian/Alaska Native people continued to bear a disproportionately higher burden of cancer deaths, both overall and from major cancers. By educational attainment, overall cancer mortality rates were about 1.6–2.8 times higher in individuals with ≤12 years of education than in those with ≥16 years of education among Black and White men and women. These disparities by educational attainment within each race were considerably larger than the Black–White disparities in overall cancer mortality within each educational attainment, ranging from 1.03 to 1.5 times higher among Black people, suggesting a major role for socioeconomic status disparities in racial disparities in cancer mortality given the disproportionally larger representation of Black people in lower socioeconomic status groups. Of note, the largest Black–White disparities in overall cancer mortality were among those who had ≥16 years of education. By area of residence, mortality from all cancer and from leading causes of cancer death were substantially higher in nonmetropolitan areas than in large metropolitan areas. For colorectal cancer, for example, mortality rates in nonmetropolitan areas versus large metropolitan areas were 23% higher among males and 21% higher among females. By age group, the racial and geographic disparities in cancer mortality were greater among individuals younger than 65 years than among those aged 65 years and older. Many of the observed racial, socioeconomic, and geographic disparities in cancer mortality align with disparities in exposure to risk factors and access to cancer prevention, early detection, and treatment, which are largely rooted in fundamental inequities in social determinants of health. Equitable policies at all levels of government, broad interdisciplinary engagement to address these inequities, and equitable implementation of evidence-based interventions, such as increasing health insurance coverage, are needed to reduce cancer disparities.

The 2023 American Cancer Society (ACS) report on cancer disparities highlights the persistent issues related to inequities in cancer incidences and outcomes.¹ Black individuals continue to be diagnosed at higher incidence rates than White individuals with multiple cancers, including colorectal, pancreatic, lung, prostate, and cervical cancers. The report also reveals that Black patients with the same cancers as White patients have a 16%–20% higher mortality rate.

These findings highlight that disparities persist and how difficult the challenges are to address them, particularly when they cannot be attributed easily to any one factor. In the 2023 ACS report, for example, the authors looked at the impact of education on cancer mortality rates and found that those with ≤12 years of education had a 2.5 times higher rate of mortality than those with ≥16 years of education. The protective effect of years of education, however, had less effect on mortality among Black individuals with cancer, who continued to have a higher mortality rate compared with White individuals across all educational thresholds. Therefore, the higher cancer incidence rates are multiplicative for Black individuals who have multiple identities associated with worse outcomes.

The finding that Black individuals who are highly educated and still have higher cancer mortality rates brings up two important issues. The first is the devastating and pervasive impact of structural racism and minority status on the health of Black individuals regardless of socioeconomic strides and success. The authors note that these manifest as a lack of access to high-quality services, financial burdens that limit treatment, or biases that prevent screening and preventative efforts, among others.

Implicit bias on a provider and staff level can also contribute to differences in the quality of cancer care being delivered and exacerbate medical mistrust. For example, Enzinger and colleagues evaluated access to opioids among people on Medicare who were dying of cancer (n = 318,549) in the 30 days before death or hospice enrollment.² Compared with White patients, Black and Hispanic patients were less likely to receive any opioid, and, if given, they were more likely to receive a lower daily and a lower total dose. Black men also reportedly were more likely to undergo urine drug screening. According to this report, the disparities were not attenuated by adjustments for socioeconomic factors (e.g., rurality, community-level factors). The second important issue regarding access to opioids is that it emphasizes the importance of applying an intersectional lens to disparities work in order to make progress, which is something that is missing from the current analyses.

Intersectionality was originally used by Kimberlé Crenshaw in Black feminist theory as a critical framework to understand power and oppression that takes into acc

Testicular germ cell tumor (GCT) is the most common solid tumor in adolescent and young adult men. Progress in the management of GCT has been made in the last 50 years, with a substantial improvement in cure rates for advanced disease, from 25% in the 1970s to nearly 80%. However, relapsed or platinum-refractory disease occurs in a proportion, 20% of whom will die from disease progression. This article reviews the current evidence-based treatments for extracranial GCT, the acute and chronic toxic effects that may result, and highlights contemporary advances and progress in the field.

A large observational study of patients in England and Wales evaluated the effectiveness of the methylation-based multi-cancer early detection (MCED) blood test Galleri to identify over 50 types of cancer in symptomatic subjects. According to the University of Oxford researchers, who led the SYMPLIFY study, never before has an MCED test’s performance been evaluated in patients suspected of having some form of cancer.

“This is the first study to examine the performance of this blood test in a symptomatic population,” says study co-author Mark R. Middleton, PhD, professor of experimental cancer medicine, a consultant medical oncologist, and head of the Department of Oncology at the University of Oxford in the United Kingdom. “The test has been developed for screening asymptomatic people in the general population. Looking at people with symptoms is important because most people with cancer have symptoms before they present.”

Dr Middleton, who is also director of the cancer research UKOxford Centre, adds, “Often, the symptoms are vague and family physicians have to work out whom to refer for invasive tests. We were interested in seeing how [this blood test] might perform here, to see if it could help sort out who needs more tests for what symptoms.” The study appears in Lancet Oncology (doi:10.1016/S1470-2045(23)00277-2).

Each subject was referred for imaging, endoscopy, or other diagnostic tests as follow-ups for suspected gynecological, lung, lower gastrointestinal, or upper gastrointestinal cancer and other non-specific but suspicious symptoms. Each subject also provided a blood sample for DNA testing.

According to the researchers, the most frequently reported symptoms were unexplained weight loss (1318, 24.1%), erratic bowel habits (1199, 22.0%), postmenopausal bleeding (875, 16.0%), and rectal bleeding (858, 15.7%). Other symptoms included abdominal pain (794, 14.5%), other pains (580, 10.6%), dysphagia (482, 8.8%) and anemia (390, 7.1%)

The researchers found that the MCED test detected cancer signals in 323 subjects. Of these, 244 were diagnosed with cancer, a positive predictive value of 75.5% and a negative predictive value of 97.6%. The investigators found that the test’s sensitivity for cancer detection increased with more advanced cancer stages, and that there was some variation in accuracy depending on referral pathway, symptom cluster, and symptoms. In essence, they wrote that the results illustrated the importance of clinical context in interpreting the results and urged careful evaluation of each individual case.

With these caveats, researchers found that the most common cancer diagnoses of the 368 cancers detected were colorectal cancer (137, 37.2%), lung cancer (81, 22.0%), uterine cancer (30, 8.2%), oesophago-gastric cancer (22, 6.0%), and ovarian cancer (14, 3.8%).

The overall sensitivity and specificity of the MCED test for uncovering the 368 cancers was 66.3% and 98.4%, respecti

It has long been believed—but with few large-scale epidemiological studies to prove it—that ultra-processed foods can contribute to a number of cancers. A new European observational study, based on results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort study, offers more proof validating the issue. The EPIC study goes one step further by showing how diet alternatives can result in a lower risk of certain cancers. The study appears in Lancet Planetary Health (doi:10.1016/S2542-5196(23)00021-9).

The EPIC cohort study included participants from 23 universities, university hospitals, and cancer research centers in 10 European countries recruited from March 18, 1991, to July 2, 2001. The researchers administered dietary questionnaires to determine each subject’s food and drink consumption. They identified participants with cancer by checking cancer registries and other sources, such as health insurance records and follow up questioning. Participants were excluded if they had a cancer diagnosis before recruitment, and other factors they believed might distort the research. Of the more than 521,000 EPIC subjects, 450,111 were included in this study, of which 318,686 were female (70.8%) and 131,425 were male (29.2%).

“We performed a substitution analysis to assess the effect of replacing 10% of processed foods and ultra-processed foods with 10% of minimally processed foods on cancer risk at 25 anatomical sites using Cox proportional–hazards models,” the researchers wrote.

“We do not consider our study ground-breaking, since other cohorts like Nutrinet Sante, UK Biobank, etc., have published similar results,” says study author Inge Huybrechts, PhD, a nutritional epidemiologist and head of the lifestyle exposure and interventions team at the World Health Organization in Lyon, France. “However, we would like to underline that it is the largest multi-center prospective cohort study conducted so far, with multiple cancer endpoints and careful control for multiple testing that confirm that our findings are robust. In addition, we [were] the first cohort to validate our food processing indicators against food processing biomarkers, which further supports our findings” [doi: 10.3389/fnut.2022.1035580].

The researchers found that a diet that focused on minimally processed and fresh foods, including whole grains, dairy products, nonstarchy vegetables, and even coffee, may reduce the risk for developing several cancers overall, while cancer risks increased when diets included more processed and ultra-processed foods.

The study also reported that when 10% of processed foods were replaced by minimally processed foods, the risk for cancer overall was reduced by 4%, and the risk for several specific cancer types was significantly reduced, including the risk for esophageal adenocarcinoma (43%) and hepatocellular carcinoma (23%).

Substituting minimally processed foods for ultra-processed f

The American Cancer Society has updated its guideline for lung cancer screening in people who are at higher risk because of their history of smoking.

The test used to screen for lung cancer is a LDCT scan. During an LDCT scan, you lie on a table while a computed tomography scanner uses x-rays to make detailed images of your chest, including your lungs. The scan only takes a few minutes.

LDCT scans can help find abnormal areas in the lungs that may be cancer, before they start causing any symptoms. An LDCT scan is recommended once a year for lung cancer screening.

For more information about lung cancer and screening, visit the American Cancer Society (https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/detection.html).