Pathologic Response Rates after Neoadjuvant Therapy for Sarcoma: A Single Institution Study

Abstract

(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.

Is 5 the New 25? Long-Term Oncologic Outcomes From a Phase II, Prospective, 5-Fraction Preoperative Radiation Therapy Trial in Patients With Localized Soft Tissue Sarcoma

“…Pathologic complete response was also associated with improved OS (100% vs 81.2%, p=0.18) (40). Similarly in this study, therapy-related pathologic changes of ≥90% led to improved OS (100% vs. 77.9%, p=0.31).…”

“…Pathologic response to neoadjuvant therapy had been investigated in RTOG 9514, where 27% of patients who received interdigitated chemotherapy and radiation had a pathologic complete response (pCR) (39). Recent data has shown pCR such as necrosis and/or fibrosis have led to improved overall and distant recurrence-free survival (19,37,(39)(40)(41). Seldon et al, retrospectively reviewed 79 patients who received neoadjuvant radiation, chemotherapy or chemoradiation and showed that chemoradiation was associated with higher rates of pCR, as defined by ≥90% necrosis.…”

“… 39 Recent data have shown pCR such as necrosis and/or fibrosis has led to improved OS and distant recurrence-free survival. 19 , 37 , 39 , 40 , 41 Seldon et al retrospectively reviewed 79 patients who received neoadjuvant irradiation, chemotherapy, or chemoradiation, and showed that chemoradiation was associated with higher rates of pCR, as defined by ≥90% necrosis. 40 Pathologic complete response was also associated with improved OS (100% vs 81.2%, P = .18).…”

Local tumour response to neoadjuvant therapy with 2‐aminoethyl dihydrogen phosphate in dogs with soft tissue sarcoma

“…Studies in human STS and other malignancies have shown that increasing rates of treatment‐induced tumour necrosis correlate with improvement of oncological outcomes and survival. However, the relationship between pathologic response and outcomes of specific neoadjuvant treatments for STS remains indeterminate (Seldon et al., 2021).…”

“…Entrapment of serous fluid in non-cystic clefts in extensively necrotic, fluid-filled sarcomas may explain why some highly devitalised tumours increase in size after therapy and support the idea that assessment of clinical response to a given antineoplastic agent should not be based solely on tumour size (Grabellus et al, 2012). outcomes of specific neoadjuvant treatments for STS remains indeterminate (Seldon et al, 2021).…”