New research was presented at AACR 2019, American Association for Cancer Research Annual Meeting, from March 29 to April 3 in Atlanta. The features below highlight some of the studies that emerged from the conference.
Comprehensive cfDNA for Newly Diagnosed mNSCLC
Evidence shows that the number of guideline-recommended biomarkers to be assessed in patients with newly diagnosed metastatic non-small cell lung cancer (mNSCLC) is increasing and includes both predictive and prognostic targets. While cell-free DNA (cfDNA) analysis appears to be a viable alternative to tissue genotyping—particularly in tissue- or time-limited clinical scenarios—the non-inferiority of comprehensive cfDNA relative to standard of care (SOC) tissue genotyping in identifying guideline-recommended genomic biomarkers in patients with mNSCLC has not been well established. To do so, researchers asked previously untreated patients with non-squamous mNSCLC who were undergoing SOC tissue genotyping to submit a pre-treatment blood sample for cfDNA analysis. Guideline-recommended biomarkers were identified by tissue in 21.3% of patients compared with 27.3% by cfDNA. Use of cfDNA increased the number of patients with an identified biomarker by 48%. Among patients without a guideline-recommended biomarker identified by tissue of cfDNA, 12.4% had an activating KRAS alteration identified in tissue alone or concordant with cfDNA, with cfDNA increasing the number of KRAS-positive patients from 24 to 92. For FDA-approved targets, cfDNA had a positive predictive value of 100% versus tissue genotyping.
Issues With Diagnosing Young-Onset CRC
Data suggest a rapid and increase of colorectal cancer (CRC) diagnoses among young adults aged 20 to 49, despite a decrease in overall incidence and mortality. To track the self-reported clinical, psychosocial, financial, and quality-of-life experiences of young-onset CRC patients and survivors, the Colorectal Cancer Alliance conducted an annual comprehensive survey of nearly 1,200 individuals in this population. While most CRC patients older than 50 are diagnosed during early stages of the disease, survey results showed that most young-onset patients and survivors (71%) were diagnosed during advanced stages, subjecting them to aggressive therapies and a substantial decrease in quality of life that included neuropathy, anxiety, clinical depression, and sexual dysfunctions. Following symptom onset, 63% of respondents waited 3-12 months before visiting a physician, and 67% reported having seen at least two physicians (some seeing more than four) before receiving a correct CRC diagnosis. Among the 33% who saw only one physician prior to diagnosis, 17% reported being initially misdiagnosed. Patients were most commonly misdiagnosed as having hemorrhoids or inflammatory bowel disease.
Gut Microbiome, Diet & Immunotherapy Response in Melanoma Patients
While studies are increasingly assessing the gut microbiome (GM) in response to melanoma therapy, few have examined how lifestyle factors may influence features of the GM or the influence of the GM on therapeutic outcomes to common melanoma therapies. For a study, researchers characterized the GM from fecal samples of patients with melanoma and collected baseline diet information as well as probiotic and antibiotic use. GM beta diversity (BD) was compared with multivariate analysis and descriptive statistics, while Wilcoxon tests were applied to alpha diversity (AD) among treatment response groups. Among all treatment groups, baseline AD was highest in patients with complete/partial response, compared with those with stable or progressive disease. While GM did not differ significantly by age, gender, or BMI, reports of probiotic (42%) and antibiotic (29%) use at baseline were associated with lower AD. Whole grains and overall diet quality were positively correlated with pro-response bacteria, whereas added sugars and processed meat were negatively correlated. GM community structure (BD) differed by high- and low-fiber intake. Patients with high- versus low-fiber diet had higher odds of response to anti-PD1 therapy.
Surgery of Primary Site in Contemporary Metastatic HER2+ Breast Cancer
Although previous research assessing survival following primary site surgery in patients with stage IV breast cancer have produced unclear results, anti-HER therapy for metastatic HER2+ disease has been well-documented to help improve outcomes. To examine the impact of primary tumor resection on survival in HER2+ stage IV breast cancer patients in the era of HER2-targeted therapy, study investigators assessed surgical removal of the primary tumor and overall mortality hazard ratios (HRs) among more than 3,200 women in this patient population. Treatment included chemo/immunotherapy in 89%; endocrine therapy, in 38%; and radiation, in 32%. Among them, 35% underwent primary site surgery. Overall mortality HRs were significantly associated with insurance (Medicare/other government vs none/Medicaid; HR, 0.36), receipt of chemo/immunotherapy (HR, 0.76), receipt of endocrine therapy (HR, 0.70), receipt of radiation therapy (HR, 1.33), African-American versus Caucasian race/ethnicity (HR, 1.39), visceral versus bone-only metastases (HR, 1.44), and lowest versus highest income quartile (HR, 1.36). Comorbidities, clinical tumor size, and clinical nodal status were not associated with survival. Propensity score analysis showed surgery was associated with improved survival versus no surgery (HR, 0.56).
Tumor Clonal Status in NSCLC
With prior studies suggesting that intratumoral heterogeneity appears to be a major cause of resistance to therapeutic agents and treatment failure, researchers conducted a study to evaluate clonal status—which reflects intratumoral heterogenetity—in non-small cell lung cancer (NSCLC). The study team performed targeted sequencing using a customized panel comprising 70 solid tumor-associated genes on samples obtained from 99 lung adenocarcinoma cases. Although no significant relationships with stage were observed between the total number of mutations or the number of variants when classified according to the variant effect predictor, a positive correlation was found between maximum primary tumor diameter and the number of clones. The number of clones also increased with stage, with disease-free survival significantly shorter among cases in which tumors had two or more clones when compared with those in which tumors had just one clone. Multivariate analysis controlling for total number of mutations, tumor stage, gender, age, and smoking showed the number to clones to be an independent determinant of disease-free survival.