Responses Rarely Follow Neoadjuvant Radiation in Retroperitoneal Sarcoma

Between January 1, 2000, and December 31, 2020, researchers at Fox Chase Cancer Center evaluated RECIST responses to neoadjuvant radiation in patients with nonmetastatic retroperitoneal sarcoma (RPS) to determine if this therapy effectively downsized tumors before surgery.¹ The retrospective review, published in the Journal of Surgical Research, showed that favorable RECIST responses were rare and that a significant proportion of tumors increased in size during radiation therapy.

RECIST Responses

The study team analyzed imaging from 22 patients and observed only 1 partial RECIST response (4.5%). A total of 77.3% (n = 17) exhibited stable disease. While 63.6% (n = 14) of tumors decreased in size by a mean relative amount of 7.1%, 36.4% (n = 8) of tumors either remained unchanged or increased in size, with a mean relative increase of 21.9%.

Furthermore, 18.2% of patients (n = 4) met the criteria for progressive disease, showing a mean relative size increase of 38%. Prior to radiation, 10 tumors radiographically abutted or encased adjacent organs. The researchers noted no change in organ abutment following treatment.

In the study cohort, 16 patients underwent surgical resection following neoadjuvant radiation. The mean operative time was 364.2 minutes, and the average estimated blood loss was 1056.7 mL. Researchers observed that patients with progressive disease by RECIST criteria experienced longer mean operative times (397.7 minutes) compared with those with stable disease (353 minutes). Similarly, mean estimated blood loss was higher in the progressive disease group at 1125 mL vs 1015 mL for those with stable disease.

Thirteen patients (81.3%) required the resection of adjacent organs or tissue during tumor extirpation. The mean number of adjacent organs resected was 2.7 for patients with stable disease and 3.0 for those with progressive disease. Specific organs removed included the kidney, adrenal gland, colon, liver segments, and pancreas. Notably, 3 patients underwent adjacent organ resection despite having no radiographic evidence of organ involvement on preoperative imaging.

Pathological analysis revealed that all patients who underwent surgery achieved an R0 or R1 margin. Tumor invasion into proximal organs was pathologically confirmed in 3 patients (18.8%). The average size of the tumor specimens was 17.4 cm, with a range of 3.5 cm to 40 cm. While tumor necrosis was identified in 4 patients (25%), it was present in 50% of those with progressive disease compared with only 14.3% of those with stable disease. There were no 30-day readmissions or 30-day mortalities reported following these procedures.

Study Details

This single-center retrospective review (IRB#22-9070) at a National Cancer Institute-designated center included adult patients who underwent curative-intent treatment for primary RPS. The study population had a mean age of 60.8 years and was 60% female. Intensity-modulated radiation therapy (IMRT) was the most frequently used modality, with patients receiving a median dose of 5000 cGy.

Study radiologists reviewed raw imaging obtained before and after radiation to quantify absolute and relative changes in tumor size, RECIST response, and adjacent organ involvement. RECIST v1.1 definitions were used, where a partial response required a 30% decrease in the sum of target lesion diameters and progressive disease required a 20% increase. Patients with incomplete records or missing raw images were excluded.

Histologic analysis showed that:

• Liposarcoma was the most common subtype (59.1%; n = 13).
• Leiomyosarcoma accounted for 27.3% (n = 6) of the cohort.
• Other subtypes included spindle cell sarcoma and dedifferentiated liposarcoma.

The researchers also referenced larger randomized trials, such as the phase 3 EORTC-62092 (STRASS) trial (NCT01344018), which compared preoperative radiotherapy plus surgery to surgery alone.² The STRASS trial previously demonstrated that adding radiation did not improve 3-year abdominal recurrence-free survival for the overall cohort.

Safety

The researchers highlighted that tumor progression during radiation can carry significant risks. Specifically, instances of progression could lead to tumor growth that renders planned operations more morbid or potentially causes patients to miss the window for surgical intervention.

Comparative safety data from the STRASS trial showed that serious adverse events occurred in 24% of patients receiving radiotherapy plus surgery vs 10% in the surgery-only group. In that trial, the most common grade 3/4 adverse events in the radiation group included lymphopenia (77%), anemia (12%), and hypoalbuminemia (12%). One treatment-related death due to a gastropleural fistula was reported in the STRASS radiation arm.

References

1. Papai E, Crear B, Kim A, et al. RECIST responses to radiation in retroperitoneal soft tissue sarcoma: when and how often do they occur? J Surg Res. Published online December 15, 2025. doi:10.1016/j.jss.2025.11.057
2. Bonvalot S, Gronchi A, Le Péchoux C, et al. Preoperative radiotherapy plus surgery versus surgery alone for patients with primary retroperitoneal sarcoma (EORTC-62092: STRASS): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2020;21(10):1366-1377. doi:10.1016/S1470-2045(20)30446-0