High-grade soft-tissue sarcoma: optimizing injection improves MRI evaluation of tumor response.

OBJECTIVES: To determine the acquisition delay after gadolinium-chelate injection that optimizes the prediction of the histological response during anthracycline-based neoadjuvant chemotherapy (NAC) for locally advanced high-grade soft-tissue sarcomas (STS). METHODS: Thirty patients (mean age 62 years) were included in this IRB-approved study. All patients received 5-6 cycles of NAC followed by surgery. A good response was defined as ≤ 10% viable cells on histological analysis of the surgical specimen. DCE-MRI was performed before treatment (MRI0) and after two cycles (MRI1). Images were obtained every 8 s. Change in contrast enhancement (CE) between MRI0 and MRI1 was calculated for each acquisition delay 't' on the whole tumor volume. Area under the receiver-operating characteristics curves (AUROC) for change in CE was calculated at each acquisition delay, as well as the accuracy of the Choi criteria. RESULTS: There were 22 (73.3%) poor responders. Acquisition delay had a significant effect on change in CE and on the response status according to Choi (p = 0.0014 and 0.0270, respectively). The highest AUROC was obtained at t = 58 s (0.792) with an optimal threshold of a -30.5% decrease in CE. At t = 58 s, accuracy to predict a poor response was 82.8% above this threshold, while it was 72.4% and 70% with no objective response according to the Choi criteria and RECIST1.1, respectively. CONCLUSION: Optimization of acquisition delay after injection to estimate change in CE improves the prediction of histological response. For STS undergoing NAC, a 60-s delay can be recommended with MRI. KEY POINTS: • Accuracy of response criteria based on contrast enhancement, like the Choi criteria, is dependent on the acquisition delay after gadolinium-chelate injection. • DCE-MRI helps determine the optimal acquisition delay after gadolinium-chelate injection for improving evaluation of tumor response. • In soft tissue sarcoma, an acquisition delay at 60 s optimizes the evaluation of the response and accuracy of the Choi criteria.

Presentation and outcome of frequent and rare sarcoma histologic subtypes: A study of 10,262 patients with localized visceral/soft tissue sarcoma managed in reference centers.

BACKGROUND: The objective of this study was to describe characteristics at diagnosis and outcomes of adults with soft tissue sarcoma. METHODS: The authors conducted a retrospective multicenter study of 12,262 patients who were treated between January 1980 and 31 December 2013 in French Sarcoma Group centers and enrolled in the "Conticabase." Diagnoses were systematically reviewed by expert pathologists, and entities were classified according to the 2013 World Health Organization classification. Diagnostic characteristics, treatments, and outcomes are described for the entire cohort, for the subgroup of patients with translocation-related sarcomas, and for 9 different histologic subtypes. RESULTS: The results stressed the magnitude of heterogeneity among adult sarcomas. For example, compared with other sarcomas, translocation-related sarcomas (2143 tumors; 20.8%) were associated with a younger age at presentation (40.6 vs 60.0 years; P < .0001), a low rate of predisposing conditions (0.01% vs 22.3%; P < .0001), a higher rate of lymph node involvement (4.7% vs 1.3%; P < .0001), and a higher rate of synchronous metastasis (11.9% vs 6.7%; P < .001); and complete (R0) resection (41.6% vs 31.9%; P < .0001), receipt of (neo)adjuvant radiation therapy (62.6% vs 42.2%; P < .0001), and receipt of (neo)adjuvant chemotherapy (36.6% vs 22.3%; P < .0001) were significantly more frequent. Overall, translocation-related sarcomas were associated with a lower rate of local relapse (18.1% vs 26.0%; P < .0001) but a higher rate of metastatic relapse (42.0% vs 30.7%; P < .0001). CONCLUSIONS: Collaborative efforts are urgently needed to better assess the natural history and management options for every histologic subtype of sarcoma. Cancer 2018;124:1179-87. © 2017 American Cancer Society.

YWHAE rearrangement identified by FISH and RT-PCR in endometrial stromal sarcomas: genetic and pathological correlations.

Endometrial stromal sarcomas represent the second most common mesenchymal uterine tumor. The 2003 WHO classification distinguishes low-grade and undifferentiated endometrial stromal sarcomas with different prognoses. Endometrial stromal sarcomas are a genetically heterogeneous group of sarcomas harboring different cytogenetic anomalies. Recently, a fusion between the YWHAE and FAM22A/B genes subsequent to a t(10;17) (q22;p13) has been described in endometrial sarcomas with high-grade histology. We examined YWHAE rearrangements by FISH break-apart and RT-PCR in a series of 27 undifferentiated uterine stromal sarcoma without JAZF1 rearrangements. Immunohistochemistry (IHC) was carried out with a panel of antibodies (estrogen (ER) and progesterone (PR) receptors, CD10, Cyclin D1, ß-catenin, p53, and Ki-67). We identified a subgroup of endometrial sarcomas with high-grade histology and uniform morphology harboring YWHAE rearrangements. FISH break-apart was interpretable in 20 cases (74%). Twelve cases (60%) showed <10% of tumor cells with a YWHAE rearrangement, 4 cases (20%) showed between 10 and ≤20%, and 4 (20%) >20%. RT-PCR was tested on 24/27 cases (88%) and 19 cases were interpretable (79%). Five cases (26%) showed a specific fusion transcript YWHAE-FAM22A/B sequence. The best concordance rate between FISH and RT-PCR (94%) was obtained with the threshold of 20% of cells with a YWHAE rearrangement. The YWHAE-rearranged cases showed high-grade morphology with uniform appearance, spindle or round epithelioid cells, low ER and PR, CD10 expression, and a high and diffuse positivity for Cyclin D1, p53, and nuclear ß-catenin negativity. Cyclin D1 was the most sensitive marker for high-grade endometrial sarcomas with YWHAE rearrangement. All undifferentiated uterine sarcomas with pleomorphic appearances did not harbor any YWHAE rearrangements, except for one case. Overall, for endometrial sarcoma cases with high-grade morphology we recommend to test for YWHAE rearrangements by FISH break-apart, a cost- and time-efficient method, and to complete the investigation by RT-PCR in borderline cases.