March 20, 2020
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Shorter neoadjuvant radiotherapy regimen effective, safe in soft tissue sarcoma

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Anusha Kalbasi, MD
Anusha Kalbasiz

A 5-day regimen of neoadjuvant radiotherapy appeared as effective and safe as the conventional 5-week regimen for patients with soft tissue sarcoma, according to results of a prospective phase 2 study published in Clinical Cancer Research.

“Because of advances in imaging and radiation therapy delivery, we have been successful in moving away from longer treatment regimens for several cancer types, including common cancers like lung, prostate and breast cancer,” Anusha Kalbasi, MD, assistant professor of radiation oncology at UCLA Jonsson Comprehensive Cancer Center, told Healio. “Since we are able to target tumors more accurately and spare the normal tissues, we are more comfortable delivering high doses of radiation in a single treatment, and so we can condense the overall treatment time.

“Having seen these advances in more common cancers, we wanted to test whether this approach would be possible in the preoperative treatment of sarcoma,” he added. “But, we wanted to test the safety out of concern for unexpected side effects.”

The current standard of care for high-risk primary soft tissue sarcoma is surgery and, in some cases, neoadjuvant or adjuvant radiation therapy. Patients also may receive chemotherapy to lower the risk for metastases.

Preoperative radiation is preferred because previous studies have shown it to be associated with lower rates of long-term adverse events such as lymphedema, fibrosis and joint immobility, Kalbasi said. Standard preoperative treatment typically comprises 5 weeks of daily radiation Monday through Friday.

Kalbasi and colleagues enrolled 52 patients with soft tissue sarcoma of the limbs or trunk in a single-institution study to determine the safety and toxicity of a 5-day neoadjuvant radiotherapy regimen. Study participants received 30 Gy in five fractions to the primary tumor with standard margins.

Grade 2 or higher late radiation toxicity served as the study’s primary endpoint. Researchers also examined major wound complications, local recurrences and distant metastases, and they conducted exploratory analyses to evaluate germline biomarkers for wound toxicity and the effects of the study on treatment utilization.

Median follow-up was 29 months.

Results showed seven of 44 evaluable patients developed at least one grade 2 late toxicity, the most common of which were fibrosis (11%), joint stiffness (11%) and lymphedema (4%). This met the primary endpoint.

Among 35 patients evaluable for local control with at least 2 years of follow-up, two (5.7%) experienced local recurrence after surgery, which is on par with studies that employed the longer conventional regimen, according to Kalbasi.

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Sixteen of 50 patients (32%) who underwent surgery had major wound complications, a rate comparable to that observed in prospective studies of neoadjuvant radiotherapy. Researchers also found a signature defined by 19 germline single nucleotide polymorphisms in microRNA binding sites of immune and DNA damage response genes, in addition to lower extremity tumor location, could be used to predict major wound complications. Further validation of this putative germline biomarker profile could guide safer use of neoadjuvant radiotherapy, researchers wrote.

Kalbasi said Jonsson Comprehensive Cancer Center has increased use of neoadjuvant radiotherapy threefold over the past 2 years.

“We are eager to move this work forward to a larger multi-institutional trial ... to show the efficacy and safety of this approach in a large number of patients across a variety of centers,” he told Healio. – by John DeRosier

For more information:

Anusha Kalbasi, MD, can be reached at Jonsson Comprehensive Cancer Center, Sarcoma Program, UCLA; B-262 Factor Building, 700 Tiverton Ave., Los Angeles, CA 90095; email: anushakalbasi@mednet.ucla.edu.

Disclosures: Kalbasi reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.