Purpose: We aimed to evaluate the value of [⁶⁸ Ga]Ga-DOTA-FAPI-04 PET/CT for the diagnosis of recurrent soft tissue sarcoma (STS), compared with [¹⁸F]FDG PET/CT. Methods: A total of 45 patients (21 females and 24 males; median age, 46 years; range, 18–71 years) with 13 subtypes of STS underwent [¹⁸F]FDG and [⁶⁸ Ga]Ga-DOTA-FAPI-04 PET/CT examination within 1 week for assessment local relapse or distant metastasis. Positive lesions on PET/CT images were verified by biopsy or 3-month follow-up. Wilcoxon matched-pairs signed-rank test was used to compare the semiquantitative values (SUV_max and TBR) of [¹⁸F]FDG and [⁶⁸ Ga]Ga-DOTA-FAPI-04 in tumor lesions, and McNemar test was applied to test for differences of both tracers. Results: Among the 45 patients, 282 local relapses and distant metastases were identified. Compared to [¹⁸F]FDG, [⁶⁸ Ga]Ga-DOTA-FAPI-04 PET/CT detected more lesions (275 vs. 186) and outperformed in sensitivity, specificity, PPV, NPV, and accuracy for the diagnosis of recurrent lesions (P < 0.001). [⁶⁸ Ga]Ga-DOTA-FAPI-04 demonstrated significantly higher values of SUV_max and TBR than [¹⁸F]FDG PET/CT in liposarcoma (P = 0.011 and P < 0.001, respectively), malignant solitary fibrous tumor (MSFT) (P < 0.001 and P < 0.001, respectively), and interdigitating dendritic cell sarcoma (IDCS) (P < 0.001and P < 0.001, respectively). While mean SUV_max and TBR presented favorable uptake of [¹⁸F]FDG over [⁶⁸ Ga]Ga-DOTA-FAPI-04 in undifferentiated pleomorphic sarcoma (UPS) (P = 0.003 and P < 0.001, respectively) and rhabdomyosarcoma (RMS) (P < 0.001 and P < 0.001, respectively). Conclusion: [⁶⁸ Ga]Ga-DOTA-FAPI-04 PET/CT is a promising new imaging modality for recurrent surveillance of STS, and compares favorably with [¹⁸F]FDG for identifying recurrent lesions of liposarcoma, MSFT, and IDCS.

Purpose: This prospective single-arm phase II clinical trial aimed to evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) combined with ifosfamide (IFO) as the first-line treatment for patients with advanced or metastatic soft-tissue sarcoma (STS). Patients and Methods: Patients received PLD (30 mg/m2; day 1) in combination with IFO (1.8 g/m2; days 1–5) every 21 days until disease progression, unacceptable toxicities, patient death, or for up to six cycles. The primary endpoint was progression-free survival (PFS; NCT03268772). Results: Overall, 69 patients with chemotherapy-naïve advanced or metastatic STS were enrolled between May 2015 and November 2019. At a median follow-up of 47.2 months, the median PFS and overall survival (OS) were found to be 7.3 [95% confidence interval (CI): 5.7–8.9] and 20.6 (95% CI: 16.3–25.0) months, respectively. The response and disease control rates were 26.1% and 81.2%, respectively. Adverse events were manageable, and no grade 3–4 cardiotoxicities were observed. There was no significant change in left ventricular ejection fraction values between baseline and after treatment (P = 0.669). Exploratory biomarker analysis suggested NF1 single-nucleotide variant was associated with poor OS (P < 0.0001) and PFS (P = 0.044). In addition, 2 patients with BRCA2 loss progressed in the initial 2 months and died within 10 months. Improved OS was observed in homologous recombination deficiency (HRD)-negative patients compared with their HRD-positive counterparts (P = 0.0056). Conclusions: Combination therapy comprising PLD and IFO is an effective and well-tolerated first-line treatment for patients with advanced or metastatic STS.

Background: Previous studies on cancer of unknown primary (CUP) mainly focus on treatment and prognosis in western populations and lacked clinical evaluation of different IHC markers, so this study aimed to evaluate characteristics of CUP and recommend a diagnostic strategy from a single center in China. Methods and results: Data of 625 patients with CUP were retrospectively collected and reviewed. The patients ranged in age from 20 to 91 years, with a female-to-male ratio of 1.3:1. The predominant histological type was poor or undifferentiated adenocarcinomas (308; 49.3%). The results of Canhelp-Origin molecular testing for the identification of the tissue of origin in 262 of 369 patients (71.0%) were considered predictable (similarity score > 45), with the most common predicted primary tumor site being the breast (57, 21.8%). Unpredictable molecular results correlated with more aggressive clinical parameters and poor survival. Thee positivity rates of several targeted antibodies (GATA3, GCDFP15, TTF1, Napsin A, and PAX8), based on the clinically predicted site, were lower than those reported for the corresponding primary tumors. Nonetheless, TRPS1 and INSM1 were reliable markers of predicted breast carcinoma (75.0%) and neuroendocrine tumors (83.3%), respectively. P16 expression, as well as HPV and EBER testing contributed significantly to the diagnosis of squamous cell carcinomas. Survival analysis revealed that older ages (> 57), ≥ 3 metastatic sites, non-squamous cell carcinomas, bone/liver/lung metastases, unpredictable molecular results, and palliative treatment correlated with poor overall survival. Conclusions: We recommend a CUP diagnostic strategy involving the use of targeted antibody panels as per histological findings that is potentially applicable in clinical practice. The markers TRPS1, INSM1, and P16 expression, as well as HPV and EBER testing are particularly valuable in this aspect. Molecular testing is also predictive of survival rates.