Paradoxical Response to Neoadjuvant Therapy in Undifferentiated Pleomorphic Sarcoma: Increased Tumor Size on MRI Associated with Favorable Pathology.

Background/Objectives: To correlate size changes in undifferentiated pleomorphic sarcoma (UPS) on magnetic resonance imaging (MRI) after neoadjuvant chemoradiation therapy (nCRT) with pathological response, risk of local recurrence, and therapeutic regimens. Methods: This retrospective study analyzed clinical, pathological, and imaging data from 39 biopsy-proven UPS subjects. Four readers measured the tumor dimensions before and after nCRT, including two perpendicular axial diameters and the longest coronal/sagittal diameter. Three cross-sectional areas and bounding volume were also calculated. Responders (pR) were defined as having ≤10% viable cells and non-responders (pNR) as having more. Inter-reader agreement was evaluated using Kendall's concordance coefficient. Changes in tumor size were compared between pR and pNR using one-way ANOVA and Tukey's HSD test for multiple comparisons of means. Results: pR showed a greater increase in size across all measurements compared to pNR. For the longest axial diameter, the mean increase was 30% ± 35% for pR and 14% ± 31% for pNR, with a mean difference (pR-pNR) of 16% (95% CI: 6-27%, p = 0.003). In tumors treated with radiotherapy alone, pR exhibited larger size increases in all dimensions compared to pNR. In contrast, in the chemoradiation group, pR showed a slight increase, while pNR generally shrank, although these differences did not reach statistical significance. Notably, pNR with local recurrence exhibited a reduction in all tumor dimensions compared to pNR without local recurrence. Conclusions: This exploratory study suggests that tumor size changes may predict pathological response and local recurrence after nCRT in UPS; however, the small sample size limits the generalizability of these findings.