PET-CT staging affects time to treatment in sarcoma.

BACKGROUND AND OBJECTIVES: PET-CTs are being increasingly utilized in sarcoma care. This study sought to investigate the impact of PET-CT acquisition on time to treatment initiation. METHODS: The records of bone and soft tissue sarcoma patients treated at our institution were reviewed. Dates of initial presentation to a sarcoma-treating physician and dates of treatment initiation were recorded. RESULTS: Time to treatment was greater in patients (p < 0.001) with median time to treatment of 26 days (IQR 17, 36) and 20 days (IQR 12, 29) for those who did and did not undergo PET-CT, respectively. Those who underwent PET-CT in addition to a plain chest CT also had significantly increased time to treatment (p < 0.001) with median time to treatment of 27 days (IQR 17, 36) and 20 days (IQR 13, 28) for those who underwent both studies and those who underwent plain CT alone, respectively. CONCLUSIONS: Despite a statistically significant increase in time to treatment with the acquisition of a PET-CT scan, the added time is likely clinically insignificant. Additionally, PET-CT may offer additional benefits in potentially more accurate staging.

What is the clinical impact of staging and surveillance PET-CT scan findings in patients with bone and soft tissue sarcoma?

BACKGROUND AND OBJECTIVES: Positron emission tomography-computerized tomography (PET-CTs) are becoming increasingly utilized in sarcoma care, workup, and surveillance. This study aimed to describe additional PET-CT findings as well as subsequent workups and changes in the clinical course due to those results. METHODS: Patient records were retrospectively reviewed, and the additional workups and evaluations triggered by PET-CT findings were qualitatively analyzed to document their results. Additional changes in the clinical course were documented. RESULTS: A total of 183 bone and soft tissue sarcoma patients underwent PET-CT as part of staging or surveillance. Additional workup was performed in 31.5% (n = 41 of 130) patients who had positive PET-CT findings. Among these, 36.6% (n = 15 of 41) patients had clinically significant findings that altered the clinical course. Overall, 14.8% (n = 27 of 183) experienced a change in the clinical course due to PET-CT. CONCLUSION: PET-CT often highlights lesions of potential clinical importance. Additional workup, as well as changes in the clinical course, were not infrequent. Future, multi-institutional studies should address the value of PET-CT in sarcoma care.

Epigenetic targeted therapy of stabilized BAP1 in ASXL1 gain-of-function mutated leukemia.

Mutations of ASXL1, encoding a component of the BAP1 histone H2A deubiquitinase complex, occur in human myeloid neoplasms and are uniformly associated with poor prognosis. However, the precise molecular mechanisms through which ASXL1 mutations alter BAP1 activity and drive leukemogenesis remain unclear. Here we demonstrate that cancer-associated frameshift mutations in ASXL1, which were originally proposed to act as destabilizing loss-of-function mutations, in fact encode stable truncated gain-of-function proteins. Truncated ASXL1 increases BAP1 protein stability, enhances BAP1 recruitment to chromatin and promotes the expression of a pro-leukemic transcriptional signature. Through a biochemical screen, we identified BAP1 catalytic inhibitors that inhibit truncated-ASXL1-driven leukemic gene expression and impair tumor progression in vivo. This study represents a breakthrough in our understanding of the molecular mechanisms of ASXL1 mutations in leukemia pathogenesis and identifies small-molecular catalytic inhibitors of BAP1 as a potential targeted therapy for leukemia.