Analysis of the immune infiltrate in undifferentiated pleomorphic sarcoma of the extremity and trunk in response to radiotherapy: Rationale for combination neoadjuvant immune checkpoint inhibition and radiotherapy

Figures & data

Table 1. Clinico-Demographic and Treatment Characteristics of 17 Patients with Undifferentiated Pleomorphic Sarcoma of the Extremity and Trunk.

	Median (range, %)
Age, years	56.3 (20.3–83.2)
Gender
Male	11 (35%)
Female	6 (65%)
Tumor size, cm	8.7 (5.3–21.7)
Primary tumor location
Trunk	4 (23.5%)
Upper extremity	3 (17.6%)
Lower extremity	10 (58.8%)
Mitoses per 10 HPF	7.5 (3–70)
Neoadjuvant therapy
XRT only	7 (41.2%)
XRT + chemotherapy	10 (58.8%)

HPF: high-power fields

XRT: radiation therapy

Table 2. Outcomes of 17 Patients with Undifferentiated Pleomorphic Sarcoma of the Extremity and Trunk.

	Median (range, %)
RECIST response to neoadjuvant XRT
Partial response	3 (17.6%)
Stable disease	7 (41.2%)
Disease progression	7 (41.2%)
Final resection margins
R0	16 (94.1%)
R1	1 (5.9%)
Percent necrosis	20 (0–90)
Percent hyalinization	17.5 (0–95)
RFS, months	36.6 (2.3–79.3)
3-year RFS	50%
OS, months	NR (10–90.8)
3-year OS	70%
Status at last follow-up
No evidence of disease	10 (60%)
Alive with disease	2 (11.8%)
Dead of disease	4 (23.5%)
Dead, cause unknown	1 (5.9%)

NR: not reached

OS: overall survival

R0: microscopic negative margins

R1: gross complete resection with positive microscopic margins

RFS: recurrence-free survival

XRT: radiation therapy

Figure 1. Examples of treatment effect following radiotherapy of undifferentiated pleomorphic sarcoma. Representative photographs of H+E stained undifferentiated pleomorphic sarcoma of the extremity and trunk demonstrating increased tumor necrosis and hyalinization following radiotherapy. (A) Tumor with extensive hyalinization (H&E, 100x). (B) Tumor with extensive necrosis with ghost and degenerative tumor cells (H&E, 100x). (C) Tumors could also have a mix of both necrosis and hyalinization (H&E, 100x). Cytological changes consistent with treatment effect (inset, H&E, 200x) was also present in this sample.

Figure 2. Association between treatment effect following radiotherapy and survival. Increased hyalinization (A) and decreased necrosis (B) of undifferentiated pleomorphic sarcomas following radiotherapy are associated with improved recurrence-free and overall survival following surgical resection.

Figure 3. Comparison of immune infiltrate immunohistochemical studies in a pre- and post-treatment undifferentiated pleomorphic sarcoma. Representative photographs of immunostained undifferentiated pleomorphic sarcoma of the extremity and trunk. Increased CD3, CD4, CD8, CD163, FOXP3 and PD1 positive cells were seen in the post treatment specimen. Tumoral PD-L1 expression was increased.

Figure 4. Quantification of the change in the immune infiltrate following radiotherapy of undifferentiated pleomorphic sarcomas of the extremity and trunk. (A) Median CD3, CD8, CD4, FoxP3, and PD-1 positive cells prior to and following radiotherapy; (B) change in the number of CD3 positive tumor infiltrating cells, paired samples by patient; (C) change in the number of CD8 positive tumor infiltrating cells, paired samples by patient; (D) change in the number of CD4 positive tumor infiltrating cells, paired samples by patient.