CA: A Cancer Journal for Clinicians最新文献

Lung cancer screening is a proven method to detect cancers early, resulting in reduced morbidity and mortality. Guidelines regarding lung cancer screening have been published by a few groups, including the American Cancer Society (ACS) who, since 2010, have recommended for low-dose computed tomography screening for those who meet the criteria. One such criterion is years since quitting (YSQ). The 2023 update¹ incorporates significant evolutions that reflect an updated evidence base, in particular related to YSQ. In recognizing that genomic alterations from combustible tobacco exposure do not reliably reverse over time, the guideline update expands the population of those eligible for screening. Furthermore, it serves as a cautionary tale to current episodic smokers regarding the common assumption that quitting smoking removes the risk of lung cancer, particularly with the passage of time.

The rationale for this change is explained as follows: the individual risk of lung cancer does indeed decrease over time once someone quits smoking, but this reduction is relatively lower only if compared with a similar person who continues to smoke. Compared with a person who never smoked, the risk for lung cancer appears to remain three times greater, even at 20 and 30 YSQ. This introduces an entirely new cohort of people now eligible for lung cancer screening, some of whom we may not visualize when imagining the patient who should be contacted for annual screening. For example, picture a business executive in her 50s who previously smoked two packs per day throughout high school and into young adulthood, quitting when she became a parent at age 30 years. She smoked during college and graduate school, but that is now in the distant past. Because of her previous smoking history of 20 pack-years, she is now—for the first time ever—considered a prime candidate for lung cancer screening to reduce the potential morbidity and mortality from lung cancer.

Embedded within this update are acknowledgments of the limitations of available data. For example, large trials used in this analysis did not routinely report on race or ethnicity; and, where race was captured, the vast majority of individuals were White study volunteers. Whether the same eligibility criteria for lung cancer screening applies across races is not clear, but some data suggest that race matters, with lung cancer onset at a younger age among Black people compared to White people, and with a higher proportion of those who did not meet the critical 30 pack-year threshold to initiate lung cancer screening (compared with White people). Finally, how to identify nonsmokers who may benefit from screening is not known. This is important because it accounts for 20% of all diagnoses of lung cancer. We agree that further work into who they are is urgent.

For now, this important update is one that requires swift action at the individual, community, state, an

Lung cancer is the leading cause of mortality and person-years of life lost from cancer among US men and women. Early detection has been shown to be associated with reduced lung cancer mortality. Our objective was to update the American Cancer Society (ACS) 2013 lung cancer screening (LCS) guideline for adults at high risk for lung cancer. The guideline is intended to provide guidance for screening to health care providers and their patients who are at high risk for lung cancer due to a history of smoking. The ACS Guideline Development Group (GDG) utilized a systematic review of the LCS literature commissioned for the US Preventive Services Task Force 2021 LCS recommendation update; a second systematic review of lung cancer risk associated with years since quitting smoking (YSQ); literature published since 2021; two Cancer Intervention and Surveillance Modeling Network-validated lung cancer models to assess the benefits and harms of screening; an epidemiologic and modeling analysis examining the effect of YSQ and aging on lung cancer risk; and an updated analysis of benefit-to-radiation-risk ratios from LCS and follow-up examinations. The GDG also examined disease burden data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program. Formulation of recommendations was based on the quality of the evidence and judgment (incorporating values and preferences) about the balance of benefits and harms. The GDG judged that the overall evidence was moderate and sufficient to support a strong recommendation for screening individuals who meet the eligibility criteria. LCS in men and women aged 50–80 years is associated with a reduction in lung cancer deaths across a range of study designs, and inferential evidence supports LCS for men and women older than 80 years who are in good health. The ACS recommends annual LCS with low-dose computed tomography for asymptomatic individuals aged 50–80 years who currently smoke or formerly smoked and have a ≥20 pack-year smoking history (strong recommendation, moderate quality of evidence). Before the decision is made to initiate LCS, individuals should engage in a shared decision-making discussion with a qualified health professional. For individuals who formerly smoked, the number of YSQ is not an eligibility criterion to begin or to stop screening. Individuals who currently smoke should receive counseling to quit and be connected to cessation resources. Individuals with comorbid conditions that substantially limit life expectancy should not be screened. These recommendations should be considered by health care providers and adults at high risk for lung cancer in discussions about LCS. If fully implemented, these recommendations have a high likelihood of significantly reducing death and suffering from lung cancer in the United States.

The progression of cancer involves a critical step in which malignant cells escape from control by the immune system. Antineoplastic agents are particularly efficient when they succeed in restoring such control (immunosurveillance) or at least establish an equilibrium state that slows down disease progression. This is true not only for immunotherapies, such as immune checkpoint inhibitors (ICIs), but also for conventional chemotherapy, targeted anticancer agents, and radiation therapy. Thus, therapeutics that stress and kill cancer cells while provoking a tumor-targeting immune response, referred to as immunogenic cell death, are particularly useful in combination with ICIs. Modern oncology regimens are increasingly using such combinations, which are referred to as chemoimmunotherapy, as well as combinations of multiple ICIs. However, the latter are generally associated with severe side effects compared with single-agent ICIs. Of note, the success of these combinatorial strategies against locally advanced or metastatic cancers is now spurring successful attempts to move them past the postoperative (adjuvant) setting to the preoperative (neoadjuvant) setting, even for patients with operable cancers. Here, the authors critically discuss the importance of immunosurveillance in modern clinical cancer management.

Rutika Mehta has served on advisory boards for Bristol-Myers Squibb Company, Eli Lilly & Company, Merck, Astellas Pharma US Inc., Novartis, BostonGene, Guardant Health, SeaGen Inc., and Natera; and on a Data and Safety Monitoring Board for Arcus Biosciences outside the submitted work. Christine Walko is employed by Mission Healthcare, has stock and ownership interests in Nabriva Therapeutics, and has served on advisory boards or as a consultant for Jackson Laboratory for Genomic Medicine, Intermountain Precision Genomics, and Clarified Precision Medicine outside the submitted work. Laura Barton reports consulting fees from AstraZeneca outside the submitted work. Gregory Lauwers reports consulting fees from ALIMENTIV outside the submitted work. The remaining authors disclosed no conflicts of interest.

Eight years ago, Paula Chambers-Raney from Houston, Texas, suffered from stomach pain, blood in her stool, and anemia. Her primary care physician told her that she had hemorrhoids. Then, over the next 18 months, other clinicians told her that she might have irritable bowel syndrome, she had probably eaten something red, and she should eat more green leafy vegetables for her anemia. After losing her job because of the number of sick days she had taken, with her health still not improving, she went to her county hospital’s emergency room for a colonoscopy. “They found a baseball-sized tumor,” says Chambers-Raney. “I was 44 years old and up until then was told I was too young to have something serious like colon cancer.”

Recognizing the alarming trend of younger people being diagnosed with colorectal cancer (CRC), in 2018, the American Cancer Society, followed by other health organizations, began recommending lowering the age for screening from the age of 50 years to the age of 45 years. A new study appearing in the Journal of the National Cancer Institute (doi:10.1093/jnci/djad068) is the latest to validate this change.

In the study, the researchers looked for abdominal pain, rectal bleeding, diarrhea, and iron-deficiency anemia, with each indicating an increased risk for early-onset CRC. They sought to determine if these four symptoms—identified as red flags—might be key to the detection of early-onset CRC. To perform this work, the researchers conducted a nested case-control study from the IBM MarketScan Commercial Database, which includes individual claims data from approximately 113 million insured adults aged 18–64 years from across the United States. The primary analyses were restricted to adults aged 18–49 years with at least 2 years of continuous enrollment before the index date. For the secondary analyses, they included adults aged 50–64 years.

The primary analyses focused on identifying red-flag indications that appeared 3 months to 2 years before the index date of diagnosis. “Ultimately, the overarching objective is to improve the early detection of CRC at younger ages, which holds significant potential for improving patient outcomes,” says senior study author Yin Cao, ScD, MPH, an associate professor of surgery in the Division of Public Health Sciences of the Department of Surgery at Washington University School of Medicine in St. Louis, Missouri.

“To our knowledge, this study is among the first large-scale studies to identify predictive red-flag signs and symptoms for early-onset CRC compared to a matched control group and in comparison with signs and symptoms in people with CRC diagnosed at older ages,” she says.

The researchers found that 19.3% of people with early-onset CRC had symptoms beginning within 3 months to 2 years of their diagnosis with a median diagnostic interval of 8.7 months. In addition, 49.1% first showed symptoms within 3 months of their diagnosis. Also, the median diagnostic interva

There is encouraging news for patients with endometrial cancer based on the results of two recent phase 3 clinical trials: Immunotherapy combined with chemotherapy may appreciably increase progression-free survival for patients with advanced or recurrent endometrial cancer.

Both trials—NRG-GY018 and RUBY— were presented at the Society of Gynecologic Oncology 2023 Annual Meeting on Women’s Cancer in Tampa, Florida. Both also appear in The New England Journal of Medicine.

The NRG-GY018 trial (doi:10.1056/NEJMoa2302312) was a double-blind, placebo-controlled, randomized study. Enrolled were 816 volunteers with stage III/IVA, stage IVB, or recurrent endometrial cancer who were randomized 1:1 to receive either pembrolizumab—an immune checkpoint inhibitor—plus chemotherapy with paclitaxel and carboplatin or a placebo plus chemotherapy for six cycles. They then received as many as 14 cycles of maintenance pembrolizumab or placebo.

All had newly diagnosed stage III or IVA disease with Response Evaluation Criteria for Solid Tumors– measurable disease or stage IVB or recurrent endometrial cancer with or without measurable disease.

The volunteers were divided into two cohorts: those who had mismatch repair–deficient (dMMR) disease and those who had mismatch repair–proficient (pMMR) disease. The primary outcome was progression-free survival in both cohorts. Interim analyses were scheduled after 84 events of death or progression in the cohort with dMMR disease and at least 196 events in the cohort with pMMR disease.

The double-blind, placebo-controlled RUBY trial (doi:10.1056/NEJMoa2216334) enrolled 494 patients with first recurrent or primary advanced stage III or IV endometrial cancer. Measurable disease was required for stages IIIA–C1, and 49 patients with carcinosarcoma—a rare and difficult-to-treat subset of endometrial cancer—were included. Volunteers were randomly assigned in a 1:1 ratio to receive 500 mg of dostarlimab or a placebo intravenously in combination with paclitaxel plus carboplatin. Doses were received every 3 weeks for the first six cycles. This was followed by 1000 mg of dostarlimab or the placebo intravenously every 6 weeks for up to 3 years.

Computed tomography or magnetic resonance imaging was performed every 6 weeks until Cycle 8 and then every 9 weeks until Week 52. Imaging was then performed every 12 weeks. There were 118 volunteers (23.9%) who had dMMR, microsatellite instability–high tumors.

For the NRG-GY018 study, the primary outcome was investigator-assessed progression-free survival according to the Response Evaluation Criteria for Solid Tumors (version 1.1). Key secondary outcomes included safety, overall survival, and health-related quality of life as assessed, the researchers reported.

“At 12-months, the percent of patients who were without evidence of disease progression or death in the dMMR cohort was 74% for the pembrolizumab group and 38% for the pla

Salivary gland cancers are a rare, histologically diverse group of tumors. They range from indolent to aggressive and can cause significant morbidity and mortality. Surgical resection remains the mainstay of treatment, but radiation and systemic therapy are also critical parts of the care paradigm. Given the rarity and heterogeneity of these cancers, they are best managed in a multidisciplinary program. In this review, the authors highlight standards of care as well as exciting new research for salivary gland cancers that will strive for better patient outcomes.

For patients with cancer under-going gonadotoxic therapies who wish to undergo sperm banking, distance may have an impact on their decision for making the trek from their homes to the clinic according to a new retrospective study. Overall, researchers at the University of Pittsburgh Medical Center (UPMC) found that distance seemed to play a role in whether or not men underwent fertility preservation (FP).

The study appears in JCO Oncology Practice (doi:10.1200/OP.22.00789).

The study authors note that although nearly 90% of the US population lives within a half-hour’s drive to a urologist, there is a steep dropoff for males who live close to specialists and medical centers offering FP. Lead author Daniel Pelzman, MD, resident physician at UPMC’s Department of Urology in Pittsburgh, Pennsylvania, says that this was a key reason prompting the study. “There has been so little research done about geography as a potential barrier to fertility preservation in men. We believe this is the first study to investigate whether the distances from fertility centers decreased the odds of males taking advantage of FP after referral.”

For the study, the researchers investigated male patients who were referred to the UPMC fertility clinic for FP between 2013 and 2021. Each subject had at least reached puberty, and all had FP recommended by a reproductive specialist. Semen was collected at a time chosen by the patients. Although not all patients saw a reproductive urologist before FP, all of them agreed to counseling with an FP coordinator by phone or in person.

Specifically, the study reported that for all cancer types, 73.6% (182) of the patients who lived no more than 20 miles away from the UPMC fertility clinic underwent FP. Although a slightly higher proportion of those living 20–40 miles away (70 men) underwent FP (76.1%), rates consistently dropped the farther out people lived from the UPMC fertility clinic; only 59.6% (28 of 47) of the patients who lived 40–60 miles from the clinic and 58.3% (14 of 24) of the patients who lived 80–100 miles from the clinic underwent sperm banking at the UPMC fertility clinic. Still, the researchers noted that the proportion of patients undergoing FP was consistently high (i.e., >50%). “This finding confirms that men want to pursue fertility preservation after referral, even if it is difficult logistically,” Dr Pelzman concluded.

Timothy D. Gilligan, MD, vice-chair for education and associate professor of medicine at the Cleveland Clinic’s Taussig Cancer Institute in Cleveland, Ohio, agrees that men would be more likely to complete sperm banking if there were a facility for doing so closer to where they live. “The study was not able to determine whether the men who lived farther away simply went somewhere else closer to do sperm banking, however,” he adds. “In other words, it’s possible that the men who did not complete sperm banking in Pittsburgh did complete it somewhere el

Anew study raises an alarm over polypharmacy, an issue that is not new but may become more worrisome because of an aging population and a myriad of new drugs coming to market, including cancer drugs. The study appears in Cancer (doi:10.1002/cncr.34642).

Corresponding author Erika Ramsdale, MD, MS, geriatric oncologist and associate professor of hematology/oncology in the Department of Medicine at the University of Rochester in Rochester, New York, warns that although there is some evidence that cancer treatment outcomes may be affected by taking multiple medications and/or potentially inappropriate medications (PIMs), “the research is still very sparse.”

Dr Ramsdale says that the main goal of this new study was to examine the associations between polypharmacy, PIMs, and potential drug–drug interactions (PDIs) and adverse cancer treatment outcomes in a large national cohort of older adults with advanced cancer. The authors note that polypharmacy and PIMs have suspected roles in many adverse events in older patients with cancer, including toxicities, but cause and effect links have been unclear.

This secondary analysis uses data from an earlier nationwide, multicenter, cluster-randomized study by the same team that appeared in The Lancet (doi:10.1016/S01406736(21)01789-X). Known as the Geriatric Assessment for Patients 70 Years and Older (GAP70+) study, it assessed clinician-rated grade 3–5 chemotherapy toxicity in older adults with advanced cancer who were undergoing a new cancer treatment regimen.

In the Cancer study, the authors note that a host of variables exist beyond the age and possible disabilities of the patients. Other factors that can contribute to difficulties include health care system–level issues, such as poor transitions of care, interdepartmental communication, multiple pharmacies, and “prescribing cascades.”

There were 718 patients enrolled in the study between July 2014 and March 2019 who had provided written consent. The subjects ranged in age from 70 to 94 years, were predominantly male (56.4%) and non-Hispanic White (87.5%), and had a stage III/IV solid tumor or lymphoma (87.5%). Gastrointestinal cancer was the most common type (246 patients; 34.3%), and it was followed by lung cancer (180 patients; 25.1%).

Four hundred forty of the 718 patients (61.3%) were taking five or more medications, 198 (27.6%) were taking eight or more, and 104 (14.5%) were taking more than 10. The researchers found that 447 patients (62.3%) received one or more PIMs according to the 2019 American Geriatrics Society Beers Criteria (range, 0–8 PIMs), and 206 (28.7%) received at least one PIM according to the Screening Tool of Older Persons’ Prescriptions (STOPP) criteria. All told, there were 482 patients (67.1%) with one or more PIMs.

There were 177 patients who had at least one potentially major PDI (category D or X).

The researchers found that the mean number of grade 2 or high

Patient navigation is a strategy for overcoming barriers to reduce disparities and to improve access and outcomes. The aim of this umbrella review was to identify, critically appraise, synthesize, and present the best available evidence to inform policy and planning regarding patient navigation across the cancer continuum. Systematic reviews examining navigation in cancer care were identified in the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, Cumulative Index of Nursing and Allied Health (CINAHL), Epistemonikos, and Prospective Register of Systematic Reviews (PROSPERO) databases and in the gray literature from January 1, 2012, to April 19, 2022. Data were screened, extracted, and appraised independently by two authors. The JBI Critical Appraisal Checklist for Systematic Review and Research Syntheses was used for quality appraisal. Emerging literature up to May 25, 2022, was also explored to capture primary research published beyond the coverage of included systematic reviews. Of the 2062 unique records identified, 61 systematic reviews were included. Fifty-four reviews were quantitative or mixed-methods reviews, reporting on the effectiveness of cancer patient navigation, including 12 reviews reporting costs or cost-effectiveness outcomes. Seven qualitative reviews explored navigation needs, barriers, and experiences. In addition, 53 primary studies published since 2021 were included. Patient navigation is effective in improving participation in cancer screening and reducing the time from screening to diagnosis and from diagnosis to treatment initiation. Emerging evidence suggests that patient navigation improves quality of life and patient satisfaction with care in the survivorship phase and reduces hospital readmission in the active treatment and survivorship care phases. Palliative care data were extremely limited. Economic evaluations from the United States suggest the potential cost-effectiveness of navigation in screening programs.