Pathologic Response Rates after Neoadjuvant Therapy For Sarcoma

Abstract

Purpose/Objective(s): 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 (percent) necrosis in 48 patients comparing NA-XRT, NA-CTX, and NA-CRT. We also investigated initial clinical outcomes correlated with percent necrosis. Materials/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 percent 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 percent 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 percent 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 percent necrosis with sequential NA-CRT (78%) compared to NA-CTX (51%, pZ0.049), but a trend when compared to NA-XRT (45%, pZ0.075). Evaluation of patients only receiving neoadjuvant AI revealed significantly improved percent necrosis with NA-CRT (83%) compared to either NA-CTX (44%, pZ0.011) or NA-XRT (45%, pZ0.031). At a MFU of 1.6 years we found a non-significant trend toward improved outcomes with higher percent necrosis [at 70%, OS (HRZ0.11), LC (HRZ0.34), and DF (HRZ0.61)]. Conclusion: In patients diagnosed with high-grade STS of the extremity or trunk, sequential NA-CRT followed by surgery yields greater percent 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.