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American Association for Cancer Research, April 10-15

The first week of the annual meeting of the American Association for Cancer Research was held virtually this year from April 10 to 15 and attracted participants from around the world, including scientists, cancer survivors, clinicians, allied health professionals, industry professionals, and others interested in cancer. The conference highlighted recent advances in the treatment, management, and prevention of cancer.

In one study, João Alessi, M.D., of the Dana-Farber Cancer Institute in Boston, and colleagues found that non-small cell lung cancer (NSCLC) patients receiving an immune checkpoint inhibitor who had an aneuploidy score ≤2 had higher overall response rates and longer progression-free and overall survival than those with aneuploidy scores >2.

The authors performed a retrospective analysis of cases from a single academic cancer center, which profiled targeted next-generation sequencing using the OncoPanel. Each tumor was assigned an aneuploidy score from 0 to 39 based on the number of altered chromosome arms within its cells. The researchers used this information to explore whether the aneuploidy score was linked to the effectiveness of treatment. The study provided an improved understanding of aneuploidy, including clinicopathologic, genomic, and immunophenotypic correlates, and also showed that a low aneuploidy is a predictor for improved immunotherapy efficacy in NSCLC.

"Of note, we found no impact of low aneuploidy among metastatic NSCLC cases who were treated with first-line chemotherapy," Alessi said. "In a separate cohort, we observed that tumors with low aneuploidy scores had significantly higher numbers of immune cells positive for the CD8, Foxp3, and programmed death ligand 1 (PD-1) proteins. The presence of these inflammatory markers indicates that tumors with low aneuploidy may be more likely to come under immune system attack than those with higher aneuploidy levels, which could contribute to increased responses to immune checkpoint inhibition."

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In another study, Emily Blauel-Bocko, M.D., of the Children's Hospital of Philadelphia, and colleagues identified rare pathogenic germline variants in patients with sporadic pediatric neuroblastoma and, for the first time, assessed whether these variants are inherited or acquired de novo.

The authors performed sequencing for a large and unselected population of neuroblastoma patient-parent triads and dyads as well as matched tumor DNA and RNA samples. This included 556 patients with 457 triads and 99 dyads, all of whom underwent whole genome sequencing of germline samples. More than half of the cohort had tumors sequenced with whole genome sequencing (336), whole exome sequencing (326), and RNA sequencing (207). Pathogenic/likely pathogenic variants in a preselected list of 197 cancer predisposition genes were then identified. The researchers found that 16 percent of the cohort harbored a pathogenic/likely pathogenic germline variant in a cancer predisposition gene. In addition, the vast majority (94 percent) of these pathogenic/likely pathogenic variants were found to be inherited, with equal maternal versus paternal inheritance patterns.

"In addition, we discovered that the presence of a pathogenic/likely pathogenic variant is associated with worse outcomes, in terms of event-free survival and overall survival, in a statistically significant manner," Blauel-Bocko said. "These findings absolutely heighten our concern for patients with such germline variants. However, as this is a new finding, the application to risk assignment, treatment decisions, and general counseling has yet to be evaluated."

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Patrick Forde, M.D., of the Sidney Kimmel Comprehensive Cancer Center and Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins University in Baltimore, and colleagues found that the addition of nivolumab to chemotherapy prior to surgery may be a viable treatment option for resectable lung cancer at high risk for recurrence.

The researchers enrolled 358 patients who were randomly assigned to either three cycles of chemotherapy or three cycles of chemotherapy with nivolumab (an anti-PD-1 immunotherapy drug). After treatment, the participants underwent surgical resection of their tumors. The primary end points of the study were pathological complete response and event-free survival. The researchers found that the addition of nivolumab to chemotherapy increased the pathological complete response rate from 2.2 to 24 percent and was not associated with any increase in toxicity.

"In a subset analysis, DNA from the tumor detected in patients' blood cleared at a higher rate in patients treated with chemo-nivolumab, and those patients who did clear tumor DNA were more likely to have a pathological complete response," Forde said. "While we await longer term survival results, the pathological complete response and absence of any increased toxicity when adding nivolumab to chemotherapy prior to surgery are very encouraging."

The study was supported by Bristol Myers Squibb, the manufacturer of nivolumab.

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Andreana N. Holowatyj, Ph.D., of the Vanderbilt University School of Medicine and Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, and colleagues discovered potential biological determinants in early-onset microsatellite stable colorectal cancer according to race.

The authors included clinical-grade targeted sequencing and clinico-demographic data from more than 6,000 cases of colorectal adenocarcinoma from the AACR Project GENIE consortium. They explored tumor mutational burden and genomic patterns of early-onset colorectal cancer by race using multivariable regression models adjusted for sex, site and histology, sequencing assay, sample type, and tumor mutational burden. The researchers observed differences in tumor mutational burden by race among cases with early-onset microsatellite stable colorectal cancer, as non-Hispanic Blacks, but not Asians or Pacific Islanders, had a significantly higher tumor mutational burden compared with Whites.

"We also identified distinct genomic patterns of early-onset microsatellite stable colorectal cancer by race. Unique LRP1B, TGFBR2, APC, and PIK3CA nonsilent mutation frequencies were observed in microsatellite stable colorectal cancers among young patients across racial groups," Holowatyj said. "The higher tumor mutational burden in tumors of Black patients with early-onset microsatellite stable colorectal cancer yields potential clinical implications upon validation. Furthermore, there is potential to target these distinct molecular characteristics via therapeutic modalities which could facilitate precision medicine and close the gaps in health disparities for young patients diagnosed with colorectal cancer."

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AACR: Ovarian Cancer Patients at Higher Risk for Mental Illness

THURSDAY, April 15, 2021 -- Women diagnosed with ovarian cancer are more than three times more likely to be diagnosed with mental illnesses, such as anxiety, depression, and adjustment disorder, compared with the general public, according to a study presented during Week 1 of the annual meeting of the American Association for Cancer Research, held virtually from April 10 to 15.

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AACR: Copanlisib + Rituximab Slows Relapsed Indolent Lymphoma

TUESDAY, April 13, 2021 -- Copanlisib plus rituximab reduces disease progression or death in patients with relapsed indolent non-Hodgkin lymphoma, according to a study presented during Week 1 of the annual meeting of the American Association for Cancer Research, held virtually from April 10 to 15.

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AACR: Personalized Vaccine for Cancer Tolerated, Feasible

MONDAY, April 12, 2021 -- A personalized vaccine can be synthesized and is feasible for administration to patients with cancer, according to a study presented during Week 1 of the annual meeting of the American Association for Cancer Research, held virtually from April 10 to 15.

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AACR: Healthy Lifestyle May Counter High Genetic Risk for Lethal Prostate Cancer

MONDAY, April 12, 2021 -- Genetic factors are associated with an increased risk for overall and lethal prostate cancer, and adherence to a healthy lifestyle can reduce the risk for lethal disease among men in the highest genetic risk quartile, according to a study presented during Week 1 of the annual meeting of the American Association for Cancer Research, held virtually from April 10 to 15.

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