Inadequate Uptake of USPSTF-Recommended Low Dose CT Lung Cancer Screening.

In 2023, Journal of Primary Care and Community Health published the results of 4 outstanding studies in which investigators aimed to explore and improve clinician and eligible individuals' knowledge of the rationale for lung cancer screening (LCS). Their results highlighted the underutilization of LCS, particularly for certain high risk populations, and the continued disparities in screening seen between groups of eligible individuals. Here, key findings from those 2023 Journal of Primary Care and Community Health reports, along with salient findings of other recent LCS reports, are discussed. The bases for the United States Preventive Task Force (USPSTF) LCS recommendations, barriers primary care providers face, the perspective of eligible individuals, importance of shared decision-making (SDM) and disparities between groups in LCS are reviewed along with potential strategies to ensure that more eligible individuals are offered LCS.

Rate of Pathogenic Germline Variants in Patients With Lung Cancer.

PURPOSE: Germline genetic testing (GGT) is now recommended for all patients diagnosed with ovarian or pancreatic cancer and for a large proportion of patients based solely on a diagnosis of colorectal or breast cancer. However, GGT is not yet recommended for all patients diagnosed with lung cancer (LC), primarily because of a lack of evidence that supports a significant frequency of identifying pathogenic germline variants (PGVs) in these patients. This study characterizes GGT results in a cohort of patients with LC. METHODS: We reviewed deidentified data for 7,788 patients with GGT (2015-2022). PGV frequencies were compared to a control cohort of unaffected individuals. GGT results were stratified by genomic ancestry, history of cancer, and PGV clinical actionability per current guidelines. RESULTS: Of all patients with LC, 14.9% (1,161/7,788) had PGVs. The rate was similar when restricted to patients with no cancer family history (FH) or personal history (PH) of other cancers (14.3%). PGVs were significantly enriched in BRCA2, ATM, CHEK2, BRCA1, and mismatch repair genes compared with controls. Patients of European (EUR) genomic ancestry had the highest PGV rate (18%) and variants of uncertain significance were significantly higher in patients of non-EUR genomic ancestry. Of the PGVs identified, 61.3% were in DNA damage repair (DDR) genes and 95% were clinically actionable. CONCLUSION: This retrospective study shows a LC diagnosis identifies patients with a significant likelihood of having a cancer-predisposing PGV across genomic ancestries. Enrichment of PGVs in DDR genes suggests that these PGVs may contribute to LC cancer predisposition. The frequency of PGVs among patients with LC did not differ significantly according to FH or PH of other cancers.

Family Matters: Germline Testing in Thoracic Cancers.

Most thoracic cancers arise via a series of stepwise somatic alterations driven by a well-defined carcinogen (ie, tobacco or asbestos for lung cancer and mesothelioma, respectively). A small proportion can emerge on a background of pathogenic germline variants (PGVs), which have the property of heritability. In general, PGVs may be initially suspected on the basis of the presence of specific clinical features. Such gene × environment interactions significantly increase the risk of developing lung cancer (1.5- to 3.2-fold). PGVs have been discovered involving the actionable driver oncogene, epidermal growth factor receptor (EGFR), with an EGFR T790M PGV rate of 0.3%-0.9% in the nonsquamous non-small-cell lung cancer subtype. Its appearance during routine somatic DNA sequencing in those patients who have not had a previous tyrosine kinase inhibitor should raise suspicion. In patients with sporadic mesothelioma, BAP1 is the most frequently mutated tumor driver, with a PGV rate between 2.8% and 8%, associated with a favorable prognosis. BAP1 PGVs accelerate mesothelioma tumorigenesis after asbestos exposure in preclinical models and may be partly predicted by clinical criteria. At present, routine germline genetic testing for thoracic cancers is not a standard practice. Expert genetic counseling is, therefore, required for patients who carry a PGV. Ongoing studies aim to better understand the natural history of patients harboring PGVs to underpin future cancer prevention, precise counseling, and cancer management with the goal of improving the quality and length of life.

Is It Time to Expand Our Definition of "Clinical Utility"?

Currently, genetic tests that predict cancer risk or risk of recurrence in patients who have had their cancer treated with curative intent must have proven "clinical utility" to be recommended by the organizations responsible for publishing the standard-of-care guidelines for cancer care.Based on the current definition of clinical utility, most patients are denied testing for cancer-predisposing genes or pathogenic germline variants even though germline testing has been proven as highly accurate in identifying pathogenic germline variant carriers, there are measures recommended to prevent and diagnose early cancers associated with particular PGVs, and disparities in patient access to genetic tests are well described.Similarly, despite dozens of studies demonstrating that detected circulating tumor DNA (ctDNA) after curative intention therapy of different cancer types is a highly accurate biomarker that predicts recurrence, the major organizations that publish guidelines for cancer monitoring after curative intention therapy recommend against using ctDNA assays to detect minimal residual disease and thereby predict recurrence for all solid tumor malignancies.Here, the primary reasons that these genetic tests are considered to lack proven clinical utility and the primary evidence suggesting that a broader definition of clinical utility should be considered are discussed. By expanding the definition of clinical utility, many patients will benefit from the information gained from having these genetic tests.

Precision oncology comes of age.

ABSTRACT: Each cancer has a unique fingerprint, and precision oncology can be used to more effectively fight malignancies. The identified genes, expressed RNA, and proteins expressed in patients' cancers are now used routinely to predict prognosis and inform treatment recommendations. This article describes how malignancies develop and some of the targeted drugs that can be used against them.

Primary Care Implications of the Expanded National Guidelines for Germline Testing of Patients Previously Diagnosed with Colorectal Cancer.

Colorectal cancer (CRC) is among the most common cancers diagnosed in the United States. Most patients are cured, have completed their routine surveillance in oncology clinics, and are being followed by primary care clinicians (PCCs). Those providers are tasked with discussing with these patients genetic testing for inherited cancer-predisposing genes that are called PGVs.Recently, the National Comprehensive Cancer Network (NCCN) Hereditary/Familial High-Risk Assessment: Colorectal Guidelines expert panel updated their recommendations for genetic testing. It is now recommended that all patients diagnosed with CRC before age 50 be tested and patients diagnosed at age 50 or older be considered for multigene panel testing (MGPT) for inherited cancer-predisposing PGVs.Here, I discuss the basis for the NCCN expanded genetic testing recommendations and highlight the salient controversies related to genetic testing. I also review the literature that suggests that PCCs identified more training as the measure needed before they are comfortable having complex discussions related to genetic testing with their patients.