Histological Assessment of Synovial Sarcoma Before and After TCR-T Cell Therapy and Cryoablation: A Case Report.

BACKGROUND/AIM: Cancer/testis antigens (CTAs) are well-known molecular targets with expression restricted to testicular germ cells and malignant tumors. T-cell receptor (TCR)-engineered T-cell (TCR-T) therapy against CTAs in patients with sarcoma has shown substantial progress, but resistance to TCR-T therapy remains a critical problem. In this report, we present a case of synovial sarcoma treated with TCR-T therapy targeting the New York-esophageal squamous cell carcinoma (NY-ESO)-1 protein. Histological findings were compared before and after TCR-T therapy and before and immediately after cryoablation. CASE REPORT: A 68-year-old man received additional wide resection for synovial sarcoma in the left leg. Due to multiple metastases, he was enrolled in a clinical trial of TCR-T therapy for NY-ESO-1. The tumor demonstrated a 34.9% reduction in diameter. However, disease progression occurred by day 84 after TCR-T therapy. Six months after disease progression, cryoablation was performed for right posterior rib lesion and tumor specimens were obtained by needle biopsy both before and immediately after cryoablation. Ten months after the diagnosis of disease progression, the patient died. Expression levels of NY-ESO-1, human leukocyte antigen, and immune checkpoint proteins remained unchanged before and after TCR-T therapy. Beta catenin was up-regulated in recurrent tumor tissues after TCR-T therapy compared to levels observed before TCR-T therapy. Immediately after cryoablation, immunoreactivity for NY-ESO-1 showed a slightly reduction. CONCLUSION: Up-regulation of beta-catenin in synovial sarcoma with recurrence after TCR-T therapy may be involved in T-cell exclusion and resistance to TCR-T therapy. Needle biopsy after cryoablation can be performed with sufficient pathological diagnostic accuracy including immunostaining.

Oncological outcome, functional results and costs after unplanned excision of musculoskeletal soft tissue sarcoma.

BACKGROUND: Treatment of soft tissue sarcomas (STS) should only be initiated once the diagnosis is fully established. Resection of tumors of unknown nature should be avoided. Nevertheless, specialized centers continue to face numbers of unplanned excisions (UPE) in STS. AIM: To compare oncologic and functional outcomes, number of surgeries, length of hospital stay and treatment costs of UPE versus planned excision (PE) in STS. METHOD: A retrospective single tertiary center study was performed on 201 patients. Survival, local and distant recurrence rates were compared between PE (n = 137) and UPE (n = 64). In a subgroup analysis of 60 patients, functional outcome (MSTS and TESS scores), and socio-economic impact (number of surgeries, length of hospital stay and treatment costs) in "functional planned excision" (fPE) group (n = 30) and "functional unplanned excision" (fUPE) group (n = 29) were compared. RESULTS: There was no significant difference in oncological outcome between PE and UPE. In the subgroup analysis, we found a non-significant difference in functional outcome. Patients in the fUPE had significantly more surgeries (3.5 vs. 1.4; p < 0.00001) and costs of their management was 64% higher than fPE (p = 0.048). Hospital stay was longer after fUPE but not statistically significant (18.3 days vs. 11.8 days; p = 0.13). CONCLUSION: Even though oncological and functional outcomes are comparable after PE and UPE of STS, the number of surgeries, length of hospital stay and treatment costs were higher in patients with UPE. Our data underscore the importance of specialized STS treatment centers including multidisciplinary management.

Clinicopathological assessment of T1 soft tissue sarcomas.

INTRODUCTION: Many studies have identified factors prognostic for soft tissue sarcomas of local recurrence, and distant metastasis. Several studies demonstrated that some subsets of patients could be safely treated by surgery alone, with acceptable rates of local recurrence. The aim of this study was to better clarify the necessity for adjuvant therapy and the width of the resected margin, by investigating the clinicopathological results of T1 (≤5 cm) soft tissue sarcomas. PATIENTS AND METHODS: A retrospective review was conducted in 96 adult patients treated for nonmetastatic AJCC T1 primary non-small round cell soft tissue sarcomas in our institution from 1995 to 2008. There were 49 men and 47 women ranging in age from 18 to 85 years (mean 51), and the observation period was 6-159 months (mean 52). The site of origin was the upper extremity in 21 cases, the lower extremity in 45, and the trunk in 30. Forty-four cases had high-grade malignant tumors, and 52 had low-grade malignant ones. Tumor size ranged from 0.7 to 5.0 cm (median size, 3.5 cm). Thirty-nine cases (41%) had previously undergone unplanned excision elsewhere. RESULTS: Eighty-nine (93%) of the patients were continuously free of disease, four were alive and currently free of disease, one was alive with metastasis, and two had died. The event-free survival rate at 5 years was 93.3%. The overall survival rate at 5 years was 94.1%. In 23 of the 45 cases with unplanned excisions (51%) residual tumor was found on histological examination. After definitive surgery, 92 patients (96%) had R0 margins. Four patients (4%) had R1 margins and were treated with postoperative radiotherapy. Forty-five of 51 cases after planned biopsies (88%) showed infiltrative growth microscopically. CONCLUSION: Tumor size was found to have a major impact on the prognosis of soft tissue sarcomas, emphasizing the importance of early detection and early treatment of these tumors. Most patients suffering from T1 soft tissue sarcomas might be able to avoid adjuvant therapies including radiotherapy and chemotherapy. To achieve good local control with surgery alone, an adequate surgical margin must be achieved even for small lesions.

[Assessment of prognostic factors of thoracic synovial sarcoma]. / Evaluation des facteurs pronostiques du synovialosarcome thoracique.

INTRODUCTION: Synovial sarcoma is an uncommon tumour and thoracic involvement is rare and of varying location. Clinical characteristics are dominated by pain, with a slow progression over years. Pathological and immuno-histochemical characteristics are helpful in the diagnosis but a specific translocation between chromosomes X and 18 is crucial for confirmation. Extensive surgical resection is required for cure, combined with adjuvant radiotherapy in the presence of adverse prognostic factors. CASE REPORT: We report a case of synovial sarcoma of the chest wall, responsible for chronic local pain for several years, presenting as an acute pleuropneumonitis in a 21-year-old patient. In view of the large size of the tumour, associated with a high proliferation index (Ki-67), a surgical resection was performed, together with local adjuvant radiotherapy. CONCLUSION: This case report reviews synovial sarcoma and underlines the difficulties and requirements of both diagnostic strategy and therapeutic management. Among them, an initial systematic review of prognostic factors (tumour size, mitotic activity, proliferation index, SYT-SSX type fusion, histological grade) is crucial to determine the therapeutic options.

Assessment of chemosensitivity in patients with malignant bone and soft tissue tumors using thallium-201 scintigraphy and doxorubicin binding assay.

This study was performed to compare the accumulation of thallium (Tl)-201 which is correlated with malignancy and the doxorubicin binding ability, which is correlated with chemosensitivity, in nine patients who received preoperative chemotherapy with doxorubicin and cisplatin. Tl-201 scintigraphy was performed at 15 minutes (early image) and 3 hours (delayed image) after injection of 111 MBq of Tl-201. The change of degree of the radionuclide uptake between the early and delayed images was evaluated before and after preoperative chemotherapy. The doxorubicin binding ability (%DB) to nuclear DNA in living tumor cells isolated from biopsy materials was assessed by doxorubicin binding assay. The histologic response to preoperative chemotherapy was evaluated by the percentage of tumor necrosis. Before preoperative chemotherapy no changes of Tl-201 uptake between the early and delayed images was detected in any tumors. Five patients, who had no change of Tl-201 uptake after preoperative chemotherapy, showed a poor histologic response and had a %DB ranging from 10% to 70% (mean: 36.0%). The other four patients, who had a %DB greater than 90%, showed a good histologic response. All of these four patients had decreased Tl-201 uptake after preoperative chemotherapy. This study demonstrated that doxorubicin binding assay and midcourse Tl-201 scintigraphy are useful methods to assess the response to chemotherapy early in malignant bone and soft tissue tumors.