De-intensification of Radiotherapy Possible in Rare Liposarcoma

Pam Harrison

November 17, 2020

De-intensification of preoperative radiation therapy is both effective and oncologically safe in patients with myxoid liposarcoma, an extremely rare type of soft tissue sarcoma (STS). The lower doses of radiotherapy were also associated with far less morbidity than the current radiation standard, conclude researchers reporting a nonrandomized international trial.

The DOREMY trial explored the reduced dose of 36 Gy, given in once-daily fractions of 2 Gy, five fractions per week. (The standard dose is 50 Gy.)

"The results of this trial were everything we could have hoped for," lead author Jules Lansu, PhD, the Netherlands Cancer Institute, Amsterdam, said in a statement.

"We saw that the risk of local recurrence was no greater than what we had seen in the past with the old, higher dosage treatment [and] at the same time, the risk of wound complication was halved," he added.

The study was published online November 12 in JAMA Oncology.

Setting up the DOREMY trial took some doing. As myxoid liposarcoma is such a rare cancer, affecting only about 2 individuals per every 1 million each year, it would have been practically impossible for researchers to run a conventional phase 3 clinical trial comparing the two doses of radiotherapy head to head.

But when the idea of a lower dose of radiotherapy was first discussed, there was concern that giving fewer radiotherapy sessions would increase the risk of recurrence, and would lead to litigation against the researchers.

However, the researchers point out that myxoid liposarcoma is more sensitive to radiation therapy than other histological subtypes of STS, and it "frequently exhibits a marked tumor volume reduction, in sharp contrast to other subtypes of STS in which the volumes, as a rule, remain fairly constant," they observe.

So they set out to use the lower dose of 36 Gy in once-daily, 2-Gy fractions as an alternative dose-fractionation approach of preoperative radiotherapy for myxoid liposarcoma.

The radiation delivered was intensity-modulated radiation therapy (IMRT) and patients received only 18 radiotherapy sessions instead of the standard 25.

The study enrolled 79 patients, 77 of whom underwent surgical resection following preoperative radiation treatment. The median age of the group was 45 years and 56% were male.

The median overall radiation treatment time was 23 days and the median interval between completion of radiotherapy and surgery was 44 days, the investigators note.

"Overall, resection specimens from 70 of 77 patents (91%) showed extensive pathological response," Lansu and colleagues report.

The de-intensification regimen was considered a success when 70% or more of resected specimens showed an extensive treatment response, defined as 50% or greater of the tumor volume showing signs of irradiation effects. In fact, patients themselves began to notice that after the third week of receiving radiation, their tumors were starting to shrink. "We saw the same thing in our scans," noted senior author Rick Haas, MD, PhD, also from the Netherlands Cancer Institute.

"Furthermore after 6 to 8 weeks [of treatment], our examination of residual tumor tissue under the microscope showed that almost no living tumor cells remained," Haas said in a statement. After a median follow-up of 25 months among those who underwent a limb-sparing procedure, the local control rate was 100% for all patients regardless of the extent of pathological response, investigators add.

At 1 year, progression-free survival (PFS) was 97% and at 3 years, 93%. Overall survival (OS) and disease-specific survival were essentially identical at 99% at 1 year, and 95% at 3 years, researchers add.

Wound complications of any severity were observed in 22% of the group overall, with only 17% of those with moderate or major wound complications requiring any intervention. This is lower than has been seen historically: the observed wound complication rate was approximately 35% in patients who underwent standard preoperative radiotherapy. (Lancet. 2002;359:2235-2241)

Grade 3 late toxic effects, notably edema, only occurred in two patients (3%), and when patients with less than 2 years of follow-up were excluded, the incidence of grade 2 or higher late toxic effects was 7% or less.

This is again substantially lower by at least threefold than previously reported results. (Radiother Oncol. 2005;75:48-53).

Reducing the dose of radiotherapy from the usual dose of 50 Gy to 36 Gy did not compromise the quality of the surgical technique or local tumor control, the authors point out.

"The findings of this trial suggest that a dose reduction is effective and oncologically safe, and thus 36 Gy is proposed as an acceptable alternative preoperative radiotherapy dose for myxoid liposarcoma," the authors conclude.

The researchers invite the international sarcoma community to participate in a registry to confirm the findings of the DOREMY trial in their own clinical practices.

This study was supported in part by grants from Nanobiotix, Honderdduizend Keer een Tientje Foundation, and the European Organization for Research and Treatment of Cancer–Soft Tissue and Bone Sarcoma Group. Study author Aisha Miah, MD, PhD, reported receiving grants from National Health Service (NHS) funding to the National Institute for Health Research (NIHR) Biomedical Research Centre for Cancer at The Royal Marsden Hospital and The Institute of Cancer Research during the conduct of the study. Study author Winan van Houdt, MD, PhD, reported receiving personal fees from Amgen outside the submitted work. Lansu and the remaining investigators have disclosed no relevant financial relationships.

JAMA Oncol. Published online November 12, 2020. Abstract

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