Initial Evaluation of [18F]FAPI-74 PET for Various Histopathologically Confirmed Cancers and Benign Lesions

The 18F-labeled fibroblast activation protein inhibitor (FAPI) [18F]FAPI- 74 has the benefit of a higher synthetic yield and better image resolution than 68Ga-labeled FAPI. We preliminarily evaluated the diagnostic performance of [18F]FAPI-74 PET in patients with various histopathologically confirmed cancers or suspected malignancies. Methods: We enrolled 31 patients (17 men and 14 women) with lung cancer (n = 7), breast cancer (n = 5), gastric cancer (n = 5), pancreatic cancer (n = 3), other cancers (n = 5), and benign tumors (n = 6). Twenty-seven of the 31 patients were treatment-naïve or preoperative, whereas recurrence was suspected in the remaining 4 patients. Histopathologic confirmation was obtained for the primary lesions of 29 of the 31 patients. In the remaining 2 patients, the final diagnosis was based on the clinical course. [18F]FAPI-74 PET scanning was performed 60min after the intravenous injection of [18F]FAPI-74 (240631 MBq). The [18F]FAPI-74 PET images were compared between the primary or local recurrent lesions of malignant tumors (n = 21) and nonmalignant lesions (n 5 8: type-B1 thymomas, granuloma, solitary fibrous tumor, and postoperative or posttherapeutic changes). The uptake and number of detected lesions on [18F]FAPI-74 PET were also compared with those on [18F]FDG PET for available patients (n = 19). Results: [18F]FAPI-74 PET showed higher uptake in primary lesions of various cancers than in nonmalignant lesions (median SUVmax, 9.39 [range, 1.83-25.28] vs. 3.49 [range, 2.21-15.58]; P = 0.053), but some of the nonmalignant lesions showed high uptake. [18F]FAPI-74 PET also showed significantly higher uptake than [18F]FDG PET (median SUVmax, 9.44 [range, 2.50-25.28] vs. 5.45 [range, 1.22-15.06] in primary lesions [P 5 0.010], 8.86 [range, 3.51-23.33] vs. 3.84 [range, 1.01-9.75] in lymph node metastases [P 5 0.002], and 6.39 [range, 0.55-12.78] vs. 1.88 [range, 0.73-8.35] in other metastases [P 5 0.046], respectively). In 6 patients, [18F]FAPI-74 PET detected more metastatic lesions than [18F]FDG PET. Conclusion: [18F]FAPI-74 PET showed higher uptake and detection rates in primary and metastatic lesions than did [18F]FDG PET. [18F]FAPI-74 PET is a promising novel diagnostic modality for various tumors, especially for precise staging before treatment, including characterization of tumor lesions before surgery. Moreover, 18F-labeled FAPI ligand might serve a higher demand in clinical care in the future.This research was originally published in JNM. Tadashi Watabe, Sadahiro Naka, Mitsuaki Tatsumi et.al. Initial Evaluation of [18F]FAPI-74 PET for Various Histopathologically Confirmed Cancers and Benign Lesions. J Nucl Med. 2023, 64(8), 1225-1231. © SNMMI

Constrained clusters of gene expression profiles with pathological features

Motivation: Gene expression profiles should be useful in distinguishing variations in disease, since they reflect accurately the status of cells. The primary clustering of gene expression reveals the genotypes that are responsible for the proximity of members within each cluster, while further clustering elucidates the pathological features of the individual members of each cluster. However, since the first clustering process and the second classification step, in which the features are associated with clusters, are performed independently, the initial set of clusters may omit genes that are associated with pathologically meaningful features. Therefore, it is important to devise a way of identifying gene expression clusters that are associated with pathological features. Results: We present the novel technique of “itemset constrained clustering ”(IC-Clustering), which computes the optimal cluster that maximises the interclass variance of gene expression between groups, which are divided according to the restriction that only divisions that can be expressed using common features are allowed. This constraint automatically labels each cluster with a set of pathological features that characterize that cluster. When applied to liver cancer datasets, IC-Clustering revealed informative gene expression clusters, which could be annotated with various pathological features, such as “tumor ” and “man”, or “except tumor ” and “normal liver function. ” In contrast, the k-means method overlooked these clusters. Supplementary Information: Our dataset is available on the following web page

Neoadjuvant chemotherapy for locally advanced gastric cancer in Japan: Consensus meeting at the 77th general meeting of the Japanese Society of Gastroenterological Surgery

Abstract Treatment strategy for locally advanced gastric cancer differs worldwide. Neoadjuvant chemotherapy (NAC) is considered one of the promising treatment options for locally advanced gastric cancer, even in Japan, and clinical trials have been conducted or are ongoing. A consensus meeting was organized at the 77th general meeting of the Japanese Society of Gastroenterological Surgery in 2022, in which the current status and future prospects of NAC for locally advanced gastric cancer were discussed. Participants at the meeting looked forward to the results of the JCOG1509 trial, providing solid evidence regarding NAC. The optimal indications and regimens for NAC were also debated. Patients with cStage III gastric cancer are the main targets of NAC in Japan, and a doublet regimen of S‐1 and oxaliplatin was preferred by the participants. However, the feasibility of a triplet regimen with S‐1, oxaliplatin, and docetaxel, and that with 5‐FU, leucovorin, oxaliplatin, and docetaxel has been demonstrated, and these could become treatment options in Japan. Other points of discussion include perioperative chemotherapy to avoid peritoneal recurrence and for patients with dMMR/MSI‐high tumors. The panel regarded NAC as a promising treatment option, and NAC will become the standard treatment for cStage III gastric cancer in Japan if an ongoing clinical trial successfully demonstrates its efficacy

Re‐appraisal of the universal definition of tumor rupture among patients with high‐risk gastrointestinal stromal tumors

Abstract Aim Tumor rupture has been indicated as a risk factor for recurrence of gastrointestinal stromal tumors (GISTs). The universal definition of tumor rupture was proposed. This study evaluated whether the universal definition was more accurate in identification of GISTs with high recurrent risk than subjective judgment. Methods The study included 507 patients with high‐risk GISTs who underwent complete resection between December 2012 and December 2015. We conducted a questionnaire survey in participating institutes to re‐diagnose tumor rupture based on the universal definition according to their surgical and pathological findings. We compared the clinical outcomes of tumor rupture based on the definition to those based on the surgeon's judgment and clarified the clinical importance of the rupture. Results Sixty‐four patients were initially registered to have tumor rupture by surgeon's judgment, and it became 90 patients who had tumor rupture after reevaluation. Although there were significant differences in recurrence‐free survival (RFS) between no rupture and rupture for both initial registration and reevaluation (p = 0.002, <0.001, respectively), a significant difference in overall survival was only observed after reevaluation (p = 0.011). Tumor rupture was significantly associated with large tumor size, mixed cell type in histology, R1 resection, frequent adjuvant therapy and recurrence, but not with location, mitosis, and genotype. Adjuvant therapy more than 3 years improved RFS of patients with tumor rupture. Conclusion This study suggested that tumor rupture based on the universal definition more accurately identified GISTs with poor prognostic outcomes than the subjective judgment

Comparison of the effects of open and laparoscopic approach on body composition in gastrectomy for gastric cancer: A propensity score‐matched study

Abstract Aim To compare the effects of open (OG) and laparoscopic gastrectomy (LG) on body composition and muscle strength. Methods This study performed a propensity score matching analysis using cases from a large‐scale, multicenter, phase III randomized controlled trial concerning oral nutritional supplements after gastrectomy and analyzed both the whole and matched cohorts. Measurements of body composition and hand grip strength (HGS) were performed at baseline (preoperatively) and at 1, 2, 3, 6, and 12 months after gastrectomy. Results Of 835 patients, 275 and 560 underwent OG and LG, respectively. Skeletal muscle mass (SMM) and HGS loss were significantly lesser in the LG group than in the OG group. The propensity score‐matched analysis, including 120 pairs of patients, confirmed that the % SMM loss values at 1, 2, 3, 6, and 12 POM were −4.5%, −4.0%, −4.7%, −4.6%, and −5.8% in the OG group and −3.0%, −1.9%, −2.4%, −2.2%, and −2.7% in the LG group, respectively. The % SMM loss was significantly lesser in the LG group than in the OG group (repeated measures ANOVA p < 0.001). The HGS loss was non‐significantly smaller in the LG group than in the OG group. Conclusion Skeletal muscle mass loss was significantly lesser in the LG group than in the OG group in both cohorts, indicating that LG may be more effective than OG for maintaining muscle mass