CA: A Cancer Journal for Clinicians最新文献

A man aged 41 years who had a past medical history significant for bilateral lower extremity varicosities and a prior 20-pack-year smoking history reported several days of fatigue to his primary care physician. His family history was notable for metastatic kidney cancer in his father. On laboratory testing, he was anemic (hemoglobin, 11.2 g/dL), with iron studies suggestive of iron-deficiency anemia. He denied any melena, hematochezia, or hematuria and underwent a full workup, including colonoscopy and capsule endoscopy, which were negative for sources of occult bleeding. The patient eventually underwent computed tomography (CT) scans of the chest, abdomen, and pelvis, which demonstrated a large, heterogeneously enhancing right renal mass measuring 9.5 × 8.2 × 6.8 cm with tumor thrombus invasion of the right renal collecting system, right renal vein, and inferior vena cava (IVC) above the hepatic veins. In addition, there was a pulmonary nodule in the left lower lobe measuring 0.8 cm, which was believed to be concerning for metastatic disease and subcentimeter retroperitoneal lymph nodes. One month later, he proceeded with a CT-guided biopsy of the pulmonary nodule at an outside hospital, with pathology revealing metastatic renal cell carcinoma (RCC). The tumor cells were positive for PAX8 and CAIX and negative for TTF1, which were suggestive of clear cell RCC (ccRCC) histology. He proceeded with a fluorodeoxyglucose F18 positron emission tomography (PET) scan for further evaluation, which demonstrated abnormal uptake in the right renal mass, a soft tissue mass in the IVC, and several small pulmonary nodules in bilateral lower lobes. His Eastern Cooperative Oncology Group (ECOG) performance status was 0. The patient was started on nivolumab plus ipilimumab (3 mg/kg and 1 mg/kg every 3 weeks, respectively), both of which are immune checkpoint inhibitors (ICIs), for intermediate-risk, metastatic RCC (according to the International Metastatic Renal Cell Carcinoma Database Consortium [IMDC] risk model) by an outside medical oncology team before presentation at Emory University Hospital.

After completing four cycles of combination immunotherapy, the patient was re-evaluated for potential cytoreductive surgery. He underwent magnetic resonance imaging (MRI) of the abdomen and pelvis for presurgical planning, most importantly as it related to the extent of the caval thrombus. The right renal mass was unchanged in size (8.8 × 6.3 × 8.7 cm); however, there was progression of the IVC tumor thrombus up to the right atrium, along with multiple (>10) new arterially enhancing lesions in the liver measuring up to 1.4 cm, compatible with metastasis (Figure 1). Transesophageal echocardiogram showed a large mass in the right atrium originating from the IVC; however, right ventricular size and function were normal, and the left ventricular ejection fraction was 60%.

In April 2023, after a multidisciplinary genitourinary tumor board, the consensus w

The concept of blood-based multicancer early detection (MCED) tests has generated much excitement, in part because of the potential of such tests to reduce cancer mortality by encompassing cancers for which screening is currently not available. A review in this issue of CA: A Cancer Journal for Clinicians, largely authored by members in the Division of Cancer Prevention at the National Cancer Institute (NCI), addresses the current status of the field.¹ The authors convey a reluctance to refer to the field as MCED. In their view and that of others, the evidence to date does not support substantial performance in detecting cancer at an early stage.² Therefore, instead, they use the designation multicancer detection (MCD) tests. The authors describe a strategy for MCD tests adopted by developers, consisting of first detecting a cancer signal based on shared biomarkers across cancer types, followed by assessment of the tissue of origin based on another set of biomarkers. The review includes a list of developers of MCD tests and the performance of tests for which data have become publicly available based on their positive and negative predictive values. The authors also provide details of the NCI Vanguard program aimed, in the short term, at testing the performance of MCD platforms they have selected among applicants and, in the longer term, at conducting prospective, randomized clinical studies.

Although the review provides an assessment of the current status of the MCD/MCED field, there is much that we do not know and that remains to be determined. From an effectiveness point of view, the optimal number of cancer types to be included may be debated. Currently, screening is available in the United States for lung, breast, colon, cervical, and prostate cancers. Screening is also available for gastric cancer in Asian countries, where the incidence is high. Although MCD tests have the potential to encompass a much broader range of cancers, notably including cancers for which screening is not available, it is clear that a relatively small number of cancers account for the vast majority of cancer deaths. American Cancer Society cancer statistics 2024 data for US cancer mortality project that five cancer types account for greater than 50% of cancer deaths.³ For men, they include pancreas and hepatobiliary cancers and, for women, pancreas and ovarian cancers. Given that an MCD test may vary in its performance by cancer type in terms of sensitivity and specificity, overall test performance may degrade with attempts to universally cover a vast number of cancer types. Moreover, for common cancers for which screening strategies are recommended, should MCD tests result in improved positive predictive value of screening programs? For other malignancies, the underlying cancer biology or treatment approaches may obviate any benefit of an MCD test. For example, the

Multicancer detection (MCD) tests use a single, easily obtainable biospecimen, such as blood, to screen for more than one cancer concurrently. MCD tests can potentially be used to improve early cancer detection, including cancers that currently lack effective screening methods. However, these tests have unknown and unquantified benefits and harms. MCD tests differ from conventional cancer screening tests in that the organ responsible for a positive test is unknown, and a broad diagnostic workup may be necessary to confirm the location and type of underlying cancer. Among two prospective studies involving greater than 16,000 individuals, MCD tests identified those who had some cancers without currently recommended screening tests, including pancreas, ovary, liver, uterus, small intestine, oropharyngeal, bone, thyroid, and hematologic malignancies, at early stages. Reported MCD test sensitivities range from 27% to 95% but differ by organ and are lower for early stage cancers, for which treatment toxicity would be lowest and the potential for cure might be highest. False reassurance from a negative MCD result may reduce screening adherence, risking a loss in proven public health benefits from standard-of-care screening. Prospective clinical trials are needed to address uncertainties about MCD accuracy to detect different cancers in asymptomatic individuals, whether these tests can detect cancer sufficiently early for effective treatment and mortality reduction, the degree to which these tests may contribute to cancer overdiagnosis and overtreatment, whether MCD tests work equally well across all populations, and the appropriate diagnostic evaluation and follow-up for patients with a positive test.

A study using data from the Danish Cancer Registry has identified risk factors among cancer survivors that might help to prevent them from developing new primary cancers, which the study calls secondary cancers. The study also has investigated whether index and second cancers might be linked. The study, from the Danish Cancer Institute in Copenhagen, Denmark, appears in Lancet Oncology (doi:10.1016/S1470-2045(23)00538-7).

Although knowledge about risk factors for the development of a patient’s first cancer, including genetic, immune, and hormonal factors as well as environmental and lifestyle risks (including smoking and alcohol use), is advancing, whether or not these issues also lead to a different cancer diagnosis is understudied. The researchers, led by Trille Kristina Kjaer, PhD, wrote that this study “aimed to investigate absolute and relative incidence of second primary cancer and examine how common etiological exposures for the first cancer were associated with development of a second cancer.”

The study included a cohort of 457,334 patients across Denmark who were diagnosed with cancer between January 1, 1997, and December 31, 2014. Each patient included in the cohort was at least 40 years old. At the time of diagnosis, their year of diagnosis, cohabitation status, income, and comorbidity were also noted, as were their genders: 50.3% (230,150) were male, and 49.7% (227,184) were female. The median age at first primary cancer was 68.3 years. Follow-up for the patients lasted up to 24 years (up to December 31, 2020).

Each patient had survived at for least 1 year after their primary cancer diagnosis had been received.

There were 27 cancer types included for both primary and secondary cancers; the relative risk of developing a new primary cancer during follow-up for the survivors was calculated with Cox proportional hazards regression.

Dr Kjaer says that it is important to note that the study was conducted in a socialized medicine society where citizens have equal access to medical treatment. As for the make-up of the cohort, she adds, “The study includes only adult cancer patients as opposed to many other studies in this field that also include childhood cancer survivors or [feature] only childhood cancer survivors. Also, we were able to take into account the competing risk of death and adjust our results for important confounders such as socioeconomic status and comorbidity.”

The researchers found that for all survivors, the incidence of a new primary cancer increased over time, from 6.3% 5 years after diagnosis to 10.5% at 10 years to 13.5% at 15 years.

Researchers found that survivors of liver, pancreatic, and lung cancer had the lowest 10-year cumulative incidence of a new primary cancer. Lung cancer was also noted to be the most frequent or second most frequent new cancer in survivors of seven of the 10 first primary cancer types associated with the highest incidence of a new cancer diagnosis

With genetic testing becoming more readily available for cancer prevention and surveillance, a new study investigated whether skipping counseling—either before or after testing—is any worse than requiring counseling for patients with a family history of cancer or those known to be at genetic risk for cancer. The results of Making Genetic Testing Accessible (MAGENTA), a four-armed randomized clinical trial, appear in JAMA Oncology (doi:10.1001/jamaoncol.2023.3748).

What prompted researchers from the University of Washington to investigate this issue was their recognition that there was low awareness of the necessity of genetic counseling in the testing process. According to the lead study author, Elizabeth Swisher, MD, a professor in the Department of Obstetrics and Gynecology and coleader of the Breast and Ovarian Cancer Research Program at the Fred Hutchinson/University of Washington Cancer Consortium in Seattle, Washington, the investigation sought to establish if skipping the standard counseling increased posttest distress and whether that would affect completing the testing process.

According to Dr Swisher, the researchers believe that MAGENTA is the first large randomized clinical trial evaluating the effect of individualized preand posttest counseling for cancer risk assessment while providing electronic enrollment, remote testing, and counseling. “As a result, we hoped to identify more accessible options for patients to get cancer genetic risk assessments without negatively impacting their worries about cancer risk.”

Study participants in all of the cohorts were found through social media and advertisements in traditional media outlets. All were enrolled between April 27, 2017, and September 29, 2020. The data analysis was performed between December 13, 2020, and May 31, 2023.

Participants were limited to English-speaking female residents of the United States who were at least 30 years old and had a family or personal history of breast or ovarian cancer. Each had to have internet access and access to a licensed health care professional. Those who had previously undergone genetic counseling were not eligible. There was no financial incentive offered.

The participants were assigned to either a family history cohort or a familial pathogenic variant (PV) cohort. The family history cohort included participants with a personal or family history of breast or ovarian cancer. To qualify for the PV cohort, participants needed a minimum of one biological relative with a PV in BRCA1, BRCA2, BRIP1, PALB2, RAD51C, RAD51D, BARD1, MSH2, MSH6, MLH1, or PMS2. There were 3125 in the family history cohort and 714 in the familial PV cohort.

The participants then watched a video about genetic testing, signed consent forms, and completed baseline questionnaires. Genetic counseling was provided by phone appointments, and testing was performed with home-delivered saliva kits. There were follow-up question

This erratum corrects the following:

Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12-49. doi:10.3322/caac.21820

Multiple errors appear in Table 9. The first age column should be “1–19” (not “1–9” as originally published), and the second age column should be “20–39” (not “20–30”). Additionally, cancer was left off as the fourth leading cause of death among men aged 40–59 years.

The authors apologize for the oversight.

Tanguy Y. Seiwert reports personal/consulting fees from AstraZeneca, EISAI INC., Inate Pharma Inc., iTeos, Merck, Regeneron Pharmaceuticals, Sanofi, and Vir; and service on a Data and Safety Monitoring Board at BioNTech outside the submitted work. Michelle D. Williams reports personal/consulting fees from Bayer Healthcare and support for other professional activities from Springer outside the submitted work. Neil D. Gross reports grants/contracts and personal/consulting fees from Regeneron Pharmaceuticals Inc.; personal/consulting fees from DragonFly Therapeutics Inc., Intuitive Surgical Inc., Merck, Replimune, and Sanofi/Genzyme US Companies; and support for other professional activities from PDS Biotechnology Corporation outside the submitted work. The remaining authors disclosed no conflicts of interest.

CA: A Cancer Journal for Clinicians (CA) was not a journal I ever saw myself publishing in let alone leading; its impact factor and prestige seemed out of reach for me—such is the Imposter Syndrome. Still, I came across the opportunity to become its editor and I applied, thinking I would regret it if I did not at least try. To my delight, I was chosen to succeed Ted Gansler, who had led CA as its editor for 23 years. Unbeknownst to me, I would also be the first to lead the journal from outside of the American Cancer Society (ACS).

CA holds a special place in medicine, and specifically in oncology. Best known for the annual publication of Cancer Statistics, it is also the reference for a diverse readership, from primary care providers to advanced practice practitioners, both within the United States and globally. Therefore, it remains important that what we publish is accessible to all—regardless of whether they are specialized in cancer medicine. With that in mind, we have instituted new instructions for our potential authors, and they are based in intentionality. Articles submitted need to be understandable to our audience, and this is an opportunity to translate technical concepts into much more accessible language. I’ve asked the authors to be cognizant that our readership includes not only diverse health professionals but also people who themselves have experienced cancer, their caregivers, and advocates. As such, patient-centric language should be used. As examples, cancer should not be used as an adjective (e.g., breast cancer patients) nor should progression on treatment be referred to as a failure. The patient experience is also one that it is important to acknowledge, and I have challenged those who intend to submit to CA to incorporate patients’ points of view in the construction and the writing of articles and to include them as authors wherever it makes sense.

As we move into the future, I hope to make use of CA to democratize the access to important information; and, in 2024, CA will begin considering publication of high-impact clinical trial results. I intend the process to be a collaboration from the start, from gaging the appropriateness of phase 3 research for CA to timely peer review and publication, while maintaining the standards set above. Although this is a major shift in the past content CA has accepted, our editorial group at ACS believe this is an important step for CA, not only because of its eminence in medical publishing but because it represents an opportunity for everyone to access information that may change the standards of care. These articles will not be restricted—they will be free and downloadable at our journal’s website, just as CA content has always been.

Most of all, I want to ensure all who read and contribute to CA that the rigorous care that Dr. Gansler provided will continue. Articles are personally reviewe

Science editor Amy H from Santa Clarita, California, was aware of her immediate family’s heavy cancer history so it came as no surprise to her when she was diagnosed with cancer—a stage 1 tumor in the transverse colon. However, nagging questions remained: Did lifestyle, environment, or other factors play a role in her diagnosis, or could her cancer possibly have been tied to a genetic history?

A new study has found that her uncertainty and anxiety are not uncommon: Most patients with cancer do not undergo germline testing to learn if their cancer may have been associated with an inherited gene mutation. The study appears in the Journal of the American Medical Association (doi:10.1001/jama.2023.9526).

For the study, researchers included patients from California and Georgia in the Surveillance, Epidemiology, and End Results (SEER) registries, who were at least age 20 years, and diagnosed with any cancer between January 1, 2013, and March 31, 2019. Genes were grouped by cancer types and recommended for testing according to the National Comprehensive Cancer Network’s practice guidelines. Four laboratories submitted gene-level interpretations while also checking nationwide for patients who may have moved to other states.

There were 1,369,602 patients selected for the study. Patient variables included sex, cancer stage at diagnosis, age at diagnosis, ethnicity, and race. They also included companion genetic testing resulted comprising 107 genes of interest. The results were classified as pathogenic, benign, or uncertain.

The patients who underwent testing varied by the following cancer types: 50% had male breast cancer, 38.6% had ovarian cancer, 26% had female breast cancer, 7.5 had more than one cancer type, 6.4% had endometrial cancer, 5.6% had pancreatic cancer, 5.6% had colorectal cancer, 1.1% had prostate cancer, and 0.3% had lung cancer.

The researchers also found that testing overall increased during the time of the study. Of particular note, they found that testing in patients with pancreatic cancer increased from 1.2% in 2013 to 18.6% in 2019. This increase was not even, however; testing for patients with lung cancer remained low, increasing only from 0.1% in 2013 to 0.8% in 2019. They also found lower rates of genetic testing in older patients; although 18% of patients age 40 years were tested, only 2% of patients at age 80 years were tested.

The study authors noted that of all the pathogenic results, 67.5% to 94.9% of gene variants were in those genes that practice guidelines recommend testing. They also found that 68.3% to 83.8% of variants identified were in genes that have been linked to cancer type. “Gastrointestinal cancer–associated genes represented 68.3% of pathogenic results in colorectal cancer and 71.8% of pathogenic results in endometrial cancer,” they wrote. “Breast and ovarian cancer–associated genes represented 79.5% of pathogenic results in female breast cancer, 83.8% in male brea

W then ophthalmologist and co-founder of Glaucomflecken LLC, William Flanary, MD, suffered two separate, unrelated bouts of cancer and then cardiac arrest, his wife served as his primary caregiver. While Dr Flanary received the medical attention he needed, Kristin Flanary, also known as Lady Glaucomflecken, co-founder and marketing director of Glaucomflecken LLC in Portland, Oregon, was left frazzled and worn down. “We discovered there’s a big discrepancy between how closely we look at how patients are doing in terms of distress versus how closely we look at how caregivers are doing.”

She is not alone in her view. It is well-accepted that cancer causes many physical, emotional, and financial burdens not only for patients, but for their caregivers as well. A new observational study has confirmed that caregivers’ needs are often overlooked, making them vulnerable.

The study by researchers at Wake Forest School of Medicine in Winston-Salem, North Carolina, appears in the Journal of the National Cancer Institute (doi:10.1093/jnci/djad198).

According to study authors, what prompted the creation of this study was the growing recognition that there was a need for better integration of caregivers into patient-centered cancer care, but to do so research was needed to evaluate the most pressing caregiving burdens and to develop strategies to ease these burdens. They noted that caregivers’ experience symptoms of at least moderate depression, anxiety, worry, and stress that can hinder their ability to help with the patient’s coping and functioning. “The practice of clinic-level distress screening may be one opportunity to improve the assessment and management of caregiver concerns,” they wrote.

For the study, the researchers worked with Wake Forest University’s NCI Community Oncology Research Program (WF NCORP) Research Base in Winston-Salem, North Carolina. NCORPs are part of a network for clinical trials and cancer care delivery research in community oncology clinics nationwide. “There are approximately 1,000 distinct sub-affiliates within 46 NCORP affiliates, many of which cluster together in organizational units or practice groups with common resources, providers, and operations,” they wrote. Data collection took place between January 2019 and June 2020.

The surveys were given to the staff member identified as the most knowledgeable about supportive care services, distress screening, and management for oncology patients at their institution. For this study, the researchers referred to them as supportive care leaders (SCLs.)

Key factors the researchers collected included the number of oncology providers, academic affiliations, the practice setting (in-patient, outpatient, freestanding outpatient, or private clinic) whether it was single or multi-specialty group, hospital affiliations, patient demographics (including age, sex, race, and ethnicity), and whether patients were enrolled in Medicaid and/or Medicare.