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Given the abundance of new research, it can be challenging to stay current on the latest advancements and findings. Oncology Times is here to help with summaries of the newest studies to ensure you are up-to-date on the latest innovations in oncology practice.



Disparities in neurotoxicity risk and outcomes among pediatric acute lymphoblastic leukemia patients

New research suggests Hispanic pediatric patients were more likely than non-Hispanic whites to develop neurotoxicity during the course of methotrexate chemotherapy for acute lymphoblastic lymphoma (ALL) (Clin Can Res 2018; doi:10.1158/1078-0432.CCR-18-0939). Between 2012 and 2017, investigators enrolled 280 newly diagnosed ALL patients from three pediatric cancer treatment centers-Texas Children's Hospital, the University of Arizona, and the University of Minnesota. The team examined medical records for suspected cases of neurotoxicity. Cox proportional hazards were utilized to estimate the association between race/ethnicity and methotrexate neurotoxicity. The data showed that 39 patients (13.9%) experienced neurotoxicity. Hispanic patients experienced neurotoxicity more than twice as often as non-Hispanic whites, after controlling for sex, age at diagnosis, body mass index, and ALL risk stratification. Nine of the 39 patients experienced a second neurotoxic event; all nine of these patients were Hispanic. Other racial/ethnic groups, including non-Hispanic black, were included in the study, but the population was too small to draw conclusions in these populations. Additionally, researchers found that patients who experienced neurotoxicity received an average of 2.25 fewer doses of intrathecal methotrexate. Six of the 39 patients (15.4%) who experienced neurotoxicity had a relapse of ALL, compared to 13 of the 241 patients (2.1%) who did not have neurotoxicity. "Hispanic ethnicity was associated with increased risk of methotrexate neurotoxicity, which was associated with treatment modifications and relapse," study authors wrote. "Understanding the mechanism and predictors of methotrexate neurotoxicity is important to improving treatment outcomes in pediatric ALL."



Disease-free and overall survival among patients with operable HER2-positive breast cancer treated with sequential vs. concurrent chemotherapy

There was no difference in disease-free survival (DFS) and overall survival (OS) among women with HER2+ breast cancer when receiving anthracycline-based chemotherapy and trastuzumab concurrently or sequentially in the neoadjuvant setting (JAMA Oncol 2018; doi:10.1001/jamaoncol.2018.3691). The randomized phase III trial enrolled 280 women with operable HER2+ invasive breast cancer at 36 centers across the country from September 2007 through December 2011. Study participants were assigned to neoadjuvant anthracycline-based chemotherapy and trastuzumab regimens, either given sequentially or concurrently. Therapy was followed by surgery. The sequential arm (Arm 1) enrolled 138 patients who received three-drug chemotherapy combination regimen known as FEC on day 1 of a 21-day cycle for 4 cycles, followed by paclitaxel plus trastuzumab weekly for 12 weeks. The concurrent arm (Arm 2) enrolled 142 patients who received paclitaxel plus trastuzumab weekly for 12 weeks, followed by FEC on day 1 of a 21-day cycle trastuzumab on days 1, 8, and 15 of the 21-day cycle for 4 cycles. All enrolled patients received a total of 1 year of trastuzumab therapy. Women with HR-positive tumors received endocrine therapy. The primary endpoint was the pCR rate in the breast. Secondary endpoints, included the pCR rate in the lymph nodes, DFS, and OS. With a median follow-up time of 5 years, researchers found no difference in either DFS or OS rates with concurrent or sequential delivery. In Arm 1, 18 women recurred and two were diagnosed with secondary cancers; 22 recurrences and three secondary cancers were diagnosed in Arm 2.



Longitudinal liquid biopsy and mathematical modeling of clonal evolution forecast time to treatment failure in the PROSPECT-C phase II colorectal cancer clinical trial

An evolutionary model utilizing serial blood samples from patients with advanced colorectal cancer treated with anti-EGFR therapies in a phase II trial could predict personalized waiting time for progression, according to recently published data (Can Discov 2018; doi:10.1158/2159-8290.CD-17-0891). Results from the PROSPECT-C trial, which evaluated biomarkers of both response and resistance to anti-EGFR therapies in patients with wild-type RAS metastatic colorectal cancer, were analyzed by the research team. Tumor biopsies were taken from patients at baseline and disease progression, and at partial response in some. Additionally, patients provided plasma samples every 4 weeks until disease progression. Researchers generated mathematical models that utilized cfDNA and carcinoembryonic antigen (CEA) levels from individual patients' plasma to predict time to progression. The results were validated using RECIST measurements from radiological imaging data. The mathematical model utilizing CEA measurements was applied to six patients to predict time to clinical progression. Of these predictions, three were within 10 percent of progression time as measured by RECIST. Data showed that predictions generated with high-sensitivity cfDNA profiling allowed for the prediction of progression time several weeks in advance, compared with models utilizing CEA measurements. "This study demonstrates how integrating frequently sampled longitudinal liquid biopsies with a mathematical framework of tumor evolution allows individualized quantitative forecasting of progression, providing novel opportunities for adaptive personalized therapies," according to investigators.



Intra-cavity stem cell therapy inhibits tumor progression in a novel murine model of medulloblastoma surgical resection

Results from early studies demonstrate how cancer-hunting stem cells, developed from skin cells, can track down and deliver a drug to destroy medulloblastoma cells hiding after surgery (PLoS One 2018; doi:10.1371/journal.pone.0198596). Researchers reported they could shrink tumors in laboratory models of medulloblastoma and extend life. The team showed the natural ability of the stem cells to be drawn to tumors, and began studying them as a way to deliver drugs to tumors and limit toxicity to the rest of the body. For the study, researchers reprogrammed skin cells into stem cells, and then genetically engineered them to manufacture a substance that becomes toxic to other cells when exposed to another drug, called a "pro-drug." Inserting the drug-carrying stem cells into the brain of laboratory models after surgery decreased the size of tumors by 15 times, and extended median survival in mice by 133 percent. Using human stem cells, they prolonged life of the mice by 123 percent, according to investigators. Additionally, the team developed a laboratory model of medulloblastoma to allow them to simulate the way standard care is currently delivered-surgery followed by drug therapy. Using this model, they discovered that after surgically removing a tumor, the cancer cells that remained grew faster. "We report a novel image-guided model of medulloblastoma resection/recurrence and provide new evidence of cytotoxic neural stem cells/induced NSCs delivered into the surgical cavity effectively target residual medulloblastoma foci."


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