Objective: This single-centre retrospective study aims to determine the incidence of therapy-induced surgical benefit in patients with non-metastatic gastrointestinal stromal tumour (GIST) treated with neoadjuvant tyrosine kinase inhibitors (TKI) and evaluate whether this can be predicted by radiological response criteria. Methods: Thirty-nine non-metastatic GIST patients were treated with neoadjuvant TKI treatment, followed by curative-intended surgery, and monitored using contrast-enhanced computed tomography (CE-CT). Surgical benefit was independently assessed by two surgical oncologists and was defined by de-escalation of surgical strategy or reduced surgical complexity. Radiological response between baseline and the last preoperative scan was determined through RECIST 1.1, Choi and volumetric criteria. Results: In this patient cohort, median neoadjuvant treatment interval was 8.3 (IQR, 3.9–10.6) months. Surgical benefit was gained in 22/39 patients. When comparing radiological criteria to findings on surgical benefit, accuracy, sensitivity, and specificity for RECIST 1.1 (90 %, 100.0 % and 82 %), Choi (64 %, 24 %, and 96 %) and volumetry (95 %, 100.0 %, and 91 %) were calculated. In 30/39 patients, temporal changes in tumour size over the course of treatment was assessed. Tumour volume reduced significantly in the surgical-benefit group compared to the non-benefit group (72 % vs. 25 %, p < 0.01) within three months. 14/19 surgical-benefit patients had an initial volume reduction above 66 %, after which volume reduced slightly with a median 3.1 % (IQR, 2.1–7.8 %) reduction. Conclusion: Surgical benefit after neoadjuvant treatment was achieved in 56 % of patients and was most accurately reflected by size-based response criteria. In patients with therapy-induced surgical benefit, nearly all treatment-induced volume reductions were achieved within three months.

Bone and soft tissue sarcomas are a group of rare malignant tumours with major histological and anatomical varieties. In a metastatic setting, sarcomas have a poor prognosis due to limited response rates to chemotherapy. Radioligand therapy targeting prostate-specific membrane antigen (PSMA) may offer a new perspective. PSMA is a type II transmembrane glycoprotein which is present in all prostatic tissue and overexpressed in prostate cancer. Despite the name, PSMA is not prostate-specific. PSMA expression is also found in a multitude of non-prostatic diseases including a subgroup of sarcomas, mostly in its neovascular endothelial cells. On PET/CT imaging, multiple sarcomas have also shown intense PSMA-tracer accumulation. PSMA expression and PSMA-tracer uptake seem to be highest in patients with aggressive and advanced sarcomas, who are also in highest need of new therapeutic options. Although these results provide a good rationale for the future use of PSMA-targeted radioligand therapy in a selection of sarcoma patients, more research is needed to gain insight into optimal patient selection methods, PSMA-targeting antibodies and tracers, administered doses of radioligand therapy, and their efficacy and tolerability. In this review, mRNA expression of the FOLH1 gene which encodes PSMA, PSMA immunohistochemistry, PSMA-targeted imaging and PSMA-targeted therapy in sarcomas will be discussed.

Genomic profiling is critical for the identification of treatment options for patients with metastatic cancer, but it remains unclear how frequently this procedure should be repeated during the course of the disease. To address this, we analyzed whole-genome sequencing (WGS) data of 250 biopsy pairs, longitudinally collected over the treatment course of 231 adult patients with a representative variety of metastatic solid malignancies. Within the biopsy interval (median, 6.4 months), patients received one or multiple lines of (mostly) standard-of-care (SOC) treatments, with all major treatment modalities being broadly represented. SOC biomarkers and biomarkers for clinical trial enrollment could be identified in 23% and 72% of biopsies, respectively. For SOC genomic biomarkers, we observed full concordance between the first and the second biopsy in 99% of pairs. Of the 219 biomarkers for clinical trial enrollment that were identified in the first biopsies, we recovered 94% in the follow-up biopsies. Furthermore, a second WGS analysis did not identify additional biomarkers for clinical trial enrollment in 91% of patients. More-frequent genomic evolution was observed when considering specific genes targeted by small-molecule inhibitors or hormonal therapies (21% and 22% of cases, respectively). Together, our data demonstrate that there is limited evolution of the actionable genome of treated metastases. A single WGS analysis of a metastatic biopsy is generally sufficient to identify SOC genomic biomarkers and to identify investigational treatment opportunities.