Pathologic response rates after neoadjuvant therapy for sarcoma.

Abstract

11060 Background: Treatment approaches for soft-tissue sarcomas (STS) vary across sarcoma centers of excellence. A multi-institutional study showed neoadjuvant doxorubicin and ifosfamide (AI) surpassed other agents in recurrence-free survival of several sarcoma subtypes. Our institution manages high-grade STS of the extremity and trunk with neoadjuvant chemotherapy (NA-CTX), neoadjuvant radiation (NA-XRT), or neoadjuvant sequential chemoradiation (NA-CRT) followed by oncologic resection and adjuvant chemotherapy. We report the pathologic (%) necrosis in 48 patients comparing NA-XRT, NA-CTX, and NA-CRT. We also investigated initial clinical outcomes correlated with % necrosis. Methods: We reviewed records of patients who received neoadjuvant therapy for sarcoma over the last four years at our center. We required a pathology report that detailed % necrosis in the specimen. We excluded the same histologies according to RTOG 9514 and RTOG 0630 protocols. There were 48 patients evaluable. The primary regimens compared were NA-CTX, NA-XRT, and NA-CRT before oncologic resection. After determining the mean % necrosis and SE for each group, we determined statistical significance through one-way ANOVA with post-hoc Tukey HSD Test. Kaplan-Meier Analysis was used to compare rates of % necrosis with OS, LC, and DF. Radiation therapy was 50Gy in 25 fractions over 5 weeks. The most common preoperative chemotherapy regimen was 3-4 cycles of AI. Results: Whole cohort evaluation found significant improvement in % necrosis with sequential NA-CRT (78%) compared to NA-CTX (51%, p = 0.049), but a trend when compared to NA-XRT (45%, p = 0.075). Evaluation of patients only receiving neoadjuvant AI revealed significantly improved % necrosis with NA-CRT (83%) compared to either NA-CTX (44%, p = 0.011) or NA-XRT (45%, p = 0.031). At a MFU of 1.6 years we found a non-significant trend toward improved outcomes with higher % necrosis [at 70%, OS (HR = 0.11), LC (HR = 0.34), and DF (HR = 0.61)]. Conclusions: In patients diagnosed with high-grade STS of the extremity or trunk, sequential NA-CRT followed by surgery yields greater % necrosis in tumors when compared to NA-CTX or NA-XRT alone. Longer follow up is required to determine if pathologic response correlates with improved outcomes.