Case Study Indicates Drug Sensitivity Testing-Guided Treatment May Improve PFS in SRMS

The drug sensitivity test-guided treatment was associated with significant improvements in the patient’s condition after 8 weeks.

A treatment approach centered around personalized functional precision oncology may yield survival benefits for patients with sclerosing and spindle cell rhabdomyosarcoma (SRMS), said researchers based on their findings from a 7-year-old patient.

Originally presenting with SRMS in 2016, the patient was diagnosed with recurrent metastatic disease in 2019 following treatment that included surgery, radiation therapy, and chemotherapy. She was subsequently enrolled in the researchers’ clinical trial that combined high-throughput drug sensitivity testing (DST) of more than 100 treatments with genomic profiling.

The DST-guided treatment was associated with significant improvements in the patient’s condition after 8 weeks, including a decrease in tumor burden, reduced metastatic disease, and improved symptoms and quality of life. Time to disease progression was 6 months, significantly longer than time to disease progression with the patient’s previous regimen (2 weeks).

“Recurrent and metastatic SRMS has a poor prognosis, with survival often measured in months (median 2-4 months),” wrote the researchers, noting that the patient died approximately 8 months following trial enrollment. “This clinical case shows the significance of developing a functional precision oncology approach, using patient material for DST—with confirmation by molecular profiling—to identify the most effective drug combination for a child with recurrent metastatic SRMS.”

Based on her molecular profiling, the patient received a combination of vincristine, irinotecan, and temozolomide (VIT). Profiling showed that the patient had mutations in cell cycle and cell division regulatory genes and the Ras signaling pathway. She also had a deletion in CDKN2A and CDKN2B, as well as the MYOD1 mutation.

For 6 months, the patient remained disease free; however, her pulmonary nodules eventually progressed, leading to lung collapse, after which she no longer received any further treatment.

“VIT is sometimes used to treat pediatric relapsed RMS; however, [progression-free survival] at 3 months is 23% (95% CI, 5.7 -46.7),” explained the researchers. “The treating oncologist would not have decided to use that regimen without guidance from the drug testing results especially because 2 of those drugs were used in upfront therapy (3 years prior). However, the clinical benefit shown on the patient corresponds to the positive activity of those drugs in the DST that was performed ex vivo,” they concluded.


De La Rocha AMA, Fader M, Coats ER, et al. Clinical utility of functional precision medicine in the management of recurrent/relapsed childhood rhabdomyosarcoma. Published online October 27, 2021. JCO Precis Oncol. doi: 10.1200/PO.20.00438