Yvonne M. Schrage

Background: The aim of this study was to describe the impact of surgical resections on tumour-infiltrating lymphocyte (TIL) therapy, based on results from a randomized phase III trial comparing TIL therapy with standard ipilimumab in patients with metastatic melanoma (NCT02278887). Methods: Surgical details of all operations performed in the trial were collected. Location, total number, and size of resected metastases were assessed in relation to successful TIL investigational medicinal product (IMP) manufacture and response to TIL therapy. Results: A total of 93 operations were needed to treat 80 patients with TIL therapy. Surgical complications were detected in 17% of operations. These were mostly mild Clavien–Dindo grade I/II complications and one Clavien–Dindo grade IIIa complication. The size or number of resected lesions did not significantly impact the TIL-IMP manufacture failure or response rate. The failure rate of TIL-IMP manufacture from lymph node metastases was 2.8% (1 of 36), which was lower than from subcutaneous metastases (19.4% (6 of 31), P = 0.037) and other sites (15.0% (3 of 20), P = 0.038). Response rates per resected lesion type were 52.9% (18 of 34) for lymph nodes, 40.9% (9 of 22) for subcutaneous lesions, 58.8% (10 of 17) for other lesions, and 60.0% (3 of 5) for combinations of lesions, without statistically significant differences. Conclusion: Tumour resections for TIL-IMP manufacture lead to limited surgical complications. Manufacture with a therapeutic response was successful using lesions of varying sizes from different anatomical locations, with highest rates for lymph nodes.

This retrospective, single-center study investigates the association between PET parameters and pathological response or disease recurrence in patients with soft tissue sarcoma (STS) treated with neoadjuvant chemotherapy (NACT). The maximum standardized uptake value (SUVmax_BL), metabolic tumor volume (MTV_BL), and total lesion glycolysis (TLG_BL) were measured at baseline [¹⁸F]FDG PET/CT and the change in percentage (ΔSUVmax, ΔMTV, ΔTLG) from baseline to early evaluation [¹⁸F]FDG PET/CT was calculated. The optimal cutoff values of the different PET parameters for pathological response, defined as 15% fibrosis/hyalinization, and recurrence-free survival were obtained for analysis. Forty-two patients who underwent baseline [¹⁸F]FDG PET/CT and NACT followed by surgery were included between January 2015 and January 2023. The primary diagnoses were angiosarcoma (n = 15), leiomyosarcoma (n = 15), sarcoma not otherwise specified (n = 9) and synovial sarcoma (n = 3). Twenty-eight (66.6%) patients underwent an early evaluation PET/CT. MTV_BL, TLG_BL, and ΔSUVmax (p = 0.024; p = 0.042, p = 0.009, respectively) values above the cutoff were associated with a pathological response based on RVT. ΔSUVmax, ΔMTV, and ΔTLG (p = 0.002; p = 0.019; p = 0.039, respectively) values above the cutoff were positively related to >15% fibrosis/hyalinization. MTV_BL, TLG_BL, and ΔMTV (p = 0.014; p = 0.022; p = 0.034, respectively) values above the cutoff were prognostic for the recurrence of disease. [¹⁸F]FDG PET/CT has a promising role in STS patients treated with NACT.

Background/Objectives: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors of the gastrointestinal (GI) tract, predominantly driven by KIT or PDGFRα oncogene mutations. Nonspecific symptoms contribute to diagnostic delays, with general practitioners (GPs) playing a pivotal role in early detection. However, studies on GIST-specific primary care pathways are limited. This study examines GP contacts, diagnoses, and prescribed drugs in primary care during the 12 months preceding GIST diagnosis. Methods: This case-control study utilized data from the Netherlands Cancer Registry and Nivel Primary Care Database. It included 294 GIST patients diagnosed between 2010 and 2020 and 576 matched cancer-free controls. GP contacts, diagnoses, and newly prescribed drugs were analyzed across two time intervals: 0–4 and 5–12 months prediagnosis. Statistical comparisons were conducted using the Wilcoxon rank-sum test and descriptive analyses. Results: GIST cases had a median of six GP contacts (IQR 4–11) in the 12 months prediagnosis versus three (IQR 2–6) for controls (p < 0.05). Contacts increased 4 months before diagnosis, peaking 1 month prior. Common diagnoses in the 4-month interval included malignant neoplasms of the stomach (27.9%) and other digestive sites (27.6% and 11.2%), abdominal pain (9.5%), and iron deficiency anemia (9.5%). Newly prescribed drugs included proton pump inhibitors (13.9%) and osmotically acting laxatives (15.0%). Conclusions: This study highlights increased GP visits and specific reasons for these visits before GIST diagnosis. Future research should further examine GP records, not only through coded data but also unstructured data, and incorporate patient and GP perspectives to explore potential improvements in the diagnostic process.

Background: Neoadjuvant imatinib therapy plays a crucial role in the management of gastrointestinal stromal tumors (GISTs), but its impact across various mutational profiles remains uncertain. Objective: The aim of this study is to describe the clinicopathological features and to assess the response and surgical outcomes of neoadjuvant imatinib in GIST patients exhibiting diverse mutational profiles. Methods: We conducted a retrospective study, extracting data from the Dutch GIST Registry, including patients treated with neoadjuvant imatinib. Response rate was the primary outcome, and secondary outcomes were the time on neoadjuvant treatment and resection margins (R0 vs. R1/R2), respectively. Results: Between 2009 and 2021, 326 patients were treated with neoadjuvant imatinib, of which 264 (80.9%) underwent resection. A total of 197 (74.6%) of them had a KIT-exon 11 mutation, 19 (7.3%) had other KIT mutations, 10 (3.8%) had PDGFRA D842 mutations, 21 (6.8%) had other PDGFRA mutations, 2 (0.7%) had NTRK mutation, 1 (0.4%) had an SDH mutation, and 17 (6.4%) had WT GISTs. Patients with KIT-exon 11 mutations demonstrated a higher rate of partial response to imatinib (60.5% vs. 33.3%; p = 0.00). A positive resection margin (R1 or R2) was observed in 14 (21.2%) patients with a non-KIT exon 11 mutations and in 11 (5.5%) patients with a KIT-exon 11 mutation (p = 0.00). Moreover, non-KIT exon 11 mutation patients had a shorter median duration of neoadjuvant therapy (5.3 months, range 0.5–21.0) compared to patients with a KIT exon 11 mutation (8.8 months, range 0.2–31.3; p < 0.001). Conclusions: Our study highlights the variability in treatment response associated with different GIST mutational profiles. Patients with a KIT-exon-11 mutation tended to respond more favorably to neoadjuvant imatinib in terms of partial response and surgical outcomes.