Soft-tissue sarcomas (STS) are a group of rare, heterogeneous, and aggressive tumors, with high metastatic risk and relatively few efficient systemic therapies. In the quest for new treatments, the immune system represents an attractive therapeutic target. Recently, PD1/PDL1 inhibitors showed very promising results in patients with solid tumors. PDL1 expression has been rarely studied in STS, in small series only, by using immunohistochemistry (IHC), and with non-concordant prognostic implications. Here, we have analyzed PDL1 mRNA expression in 758 clinical STS samples retrospectively profiled using DNA microarrays and RNAseq, and searched for correlations with clinicopathological variables including metastasis-free survival (MFS) after surgery. PDL1 expression was heterogeneous across the samples. PDL1-high samples (41%) were more frequently leiomyosarcomas and liposarcomas, and showed more frequently a complex genetic profile and a high-risk CINSARC signature. No correlation existed with other clinicopathological features such as tumor site, depth, and pathological tumor grade and size. In multivariate prognostic analysis, the PDL1-high class was associated with shorter MFS, independently of the pathological type and the CINSARC signature. Analysis of correlations with biological factors suggested the existence in tumors of the PDL1-high class of a strong and efficient cytotoxic T-cell response, however associated with some degree of T-cell exhaustion and negative regulation. In conclusion, we show that PDL1 expression refines the prediction of metastatic relapse in operated localized STS, and that PD1/PDL1 blockade holds potential to improve patient survival by reactivating inhibited T cells to increase the antitumor immune in PDL1-high tumors.

BackgroundChordomas are very rare low-grade malignant bone tumors that arise from the embryonic rests of the notochord. They are characterized by slow growth and long history with frequent local relapses, and sometimes metastases. While chemotherapy is not efficient, imatinib has shown antitumor activity.Case presentationWe report on a 76-year-old patient with EGFR-overexpressing advanced chordoma that progressed on imatinib and subsequently responded to erlotinib during 12 months.ConclusionsWe report the fourth case of advanced chordoma treated with an EGFR inhibitor. We also review the literature concerning the rationale and potential of EGFR targeting in chordoma.

Synovial sarcoma (SVS) of the thyroid gland is exceedingly rare. We report the case of a 55-year-old man with a rapidly growing 7-cm neck mass. Because of suspicion of anaplastic thyroid carcinoma, a total thyroidectomy was planned, without preoperative cytology. During surgery, the tumor ruptured, leading to fragmented and incomplete resection. The morphological and immunohistochemical aspects suggested thyroid SVS, which was confirmed by fluorescent in situ hybridization (SYT gene rearrangement). The patient experienced immediate local relapse in close contact with large vessels and the thyroid cartilage and was referred to our institution. Doxorubicin-ifosfamide chemotherapy led to a minor response that authorized secondary conservative surgery. Because of microscopically incomplete resection, adjuvant radiotherapy was chosen and is ongoing 10 months after initial surgery. The prognosis of thyroid SVS is associated with a high risk for local and metastatic relapses. Pretreatment diagnosis is fundamental and may benefit from molecular analysis. Margin-free monobloc surgical excision is the best chance for cure, but adjuvant chemotherapy and radiotherapy deserve to be discussed.

GGI refines the prediction of MFS in operated STS and might improve the tailoring of adjuvant chemotherapy. Further clinical validation is warranted in larger retrospective, then prospective series, as well as the functional validation of relevant genes that could provide new therapeutic targets.