(1) Background: Pathologic necrosis of soft tissue sarcomas (STS) has been used to determine treatment response, but its relationship to neoadjuvant treatments remains indeterminate. In this retrospective, single institution study, we hypothesized that neoadjuvant chemoradiation (NA-CRT) yields higher rates of pathologic complete response (pCR) than neoadjuvant radiation (NA-XRT) or chemotherapy (NA-CT) alone. (2) Methods: Patients with extremity STS between 2011–2020 who received neoadjuvant treatment were included. pCR was defined as percent necrosis of the surgical specimen greater than or equal to 90%. (3) Results: 79 patients were analyzed. 51.9% of the population were male with a mean age of 58.4 years. 49.4% identified as Non-Hispanic White. Twenty-six (32.9%) patients achieved pCR while 53 (67.1%) did not. NA-CT (OR 15.82, 95% CI = 2.58–96.9, p = 0.003 in univariate (UVA) and OR 24.7, 95% CI = 2.88–211.2, p = 0.003 in multivariate (MVA), respectively) and NA-XRT (OR 5.73, 95% CI = 1.51–21.8, p = 0.010 in UVA and OR 7.95, 95% CI = 1.87–33.7, p = 0.005 in MVA, respectively) was significantly associated with non- pCR when compared to NA-CRT. The analysis also demonstrated that grade 3 tumors, when using grade 2 as reference, also had significantly higher odds of achieving pCR (OR 0.23, 95% CI = 0.06–0.80, p = 0.022 in UVA and OR 0.16, 95% CI = 0.04–0.70, p = 0.015 in MVA, respectively). (4) Conclusion: NA-CRT yields superior pCR compared to other neoadjuvant regimens. This extends to higher grade tumors.

IMPORTANCE A large proportion of extremity soft-tissue sarcomas (ESS) occur among young adults, yet this group is underrepresented in clinical trials, resulting in limited data on this population. Younger patients present many complex challenges that affect clinical management. OBJECTIVE To investigate variations in treatment management in young adults vs older adults with ESS. DESIGN, SETTING, AND PARTICIPANTS This multicenter retrospective cohort study used the National Cancer Data Base (NCDB) to identify patients 18 years and older with ESS who received definitive treatment (ie, limb-sparing surgery [LSS] or amputation) between 2004 and 2014. Data analysis was conducted in November 2019. EXPOSURES Treatment regimen received among young adults (aged 18-39 years) and older adults (Ն40 years) after diagnosis with ESS. MAIN OUTCOMES AND MEASURES To detect unique factors associated with treatment decisions in young adults with ESS, multivariable analyses used logistic regressions for patterns of treatment and their association with demographic factors and tumor characteristics. RESULTSOverall, 8953 patients were identified, and among these, 1280 (14.3%) were young adults.From the full cohort, 4796 patients (53.6%) identified as male and 6615 (73.9%) identified as non-Hispanic White. More young adults than older adults underwent amputation (age 18-39 years, 104 of 1280 [8.1%]; age 40-64 years, 217 of 3937 [5.5%]; aged Ն65 years, 199 of 3736 [5.3%]), but the association was not statistically significant (age Ն65 years, odds ratio [OR], 1.49; 95% CI, 1.00-2.23; P = .05). Young adults were more likely to receive chemotherapy than older patients (age 40-65 years, OR, 0.52; 95% CI, 0.45-0.60; P = .001; Ն65 years, OR, 0.16; 95% CI, 0.12-0.20; P = .001). Conversely, young adults were less likely to receive radiation therapy compared with older

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.