Effect of Neoadjuvant Therapies on Soft Tissue Sarcomas with Tail-like Lesions: A Multicenter Retrospective Study

Abstract

Several types of soft tissue sarcomas have peripheral infiltrative growth characteristics called tail-like lesions. The efficacy of neoadjuvant therapy for tumors with tail-like lesions has not been elucidated. From 2012 to 2019, we analyzed 36 patients with soft tissue sarcoma with tail-like lesions treated with neoadjuvant therapy, including chemotherapy, radiotherapy, or both. The effect of neoadjuvant therapy on the tail sign was investigated by analyzing the change in tail-like lesions during neoadjuvant therapy and histological responses. The median length of the tail-like lesion reduced from 29.5 mm at initiation to 19.5 mm after neoadjuvant therapy. The extent of shrinkage in tail-like lesions was related to the histopathological responses in the main part of the tumor. Complete disappearance of the tail-like lesion was observed in 12 patients; however, it was not related to achieving a microscopically negative margin. The oncologic outcomes did not significantly differ between cases with and without the complete disappearance of tail-like lesions. This study indicated that the shrinkage of tail-like lesions did not have a significant effect on complete resection or improvements of clinical outcomes. A more comprehensive evaluation is needed to elaborate on the surgical strategy.

Keywords: chemotherapy; invasive front; myxofibrosarcoma; neoadjuvant therapy; radiotherapy; soft tissue sarcoma; tail-like lesion; undifferentiated pleomorphic sarcoma.

Figure 1

The rates of change in the tumor and the relationship between the main part and tail-like lesion. (a) Rates of change in maximum length of the tumor. (b) Rates of change in the length of the tail-like lesion. (c) Rates of change in the thickness of the tail-like lesion. (d) Relationship between the changes in maximum length of the main part and the length of the tail-like lesion. Squares indicate the means, and the error bars indicate the standard deviations. (e) Relationship between the rate of change in maximum length of the main part and the thickness of the tail-like lesion. (f) Relationship between the tail-like lesions’ length and thickness.

Figure 2

Waterfall plots illustrating the rates of change in the tumor with various neoadjuvant therapies. The rates of change were evaluated using the aforementioned method. (a) The rates of change in the main part of the tumor; (b) the rates of change in the length of the tail-like lesion; (c) the rates of change in the thickness of the tail-like lesion. The red bars indicate radiotherapy, blue bars indicate chemotherapy, and green bars indicate combination therapy (chemoradiotherapy); (d) the pie charts indicate the relationships between the neoadjuvant modalities and histological response (4-tier classification). For readability, grades 3 and 4 were integrated. In the Rt + Cx group, hyperthermia was added as an augmentation. A, Adriamycin; C, carboplatin; Cx, chemotherapy; D, docetaxel; E, etoposide; G, gemcitabine; Ht, hyperthermia; I, ifosfamide; P, cisplatin; Rt, radiotherapy; VDC/IE, vincristine + Adriamycin + cyclophosphamide/ifosfamide + etoposide; VIDE, vincristine + ifosfamide + Adriamycin + etoposide.

Figure 3

Box-and-whisker plots of the relationship between the histopathological evaluations and the shrinkage of tumors. (a) Relationships between the histopathological response and changes in the maximum length of the main part; (b) relationships between the histopathological response and changes in the length of the tail-like lesion; (c) relationships between the histopathological response and changes in the thickness of the tail-like lesion.

Figure 4

Kaplan–Meier curves comparing patients who underwent neoadjuvant therapy with those who did not, among UPS + MFS subtypes. (a) Overall survival, (b) local relapse-free survival, and (c) distant relapse-free survival. The red and blue lines indicate patients with and without neoadjuvant therapy, respectively.