Morten Ladekarl

Introduction Aim: Fibroblast activation protein inhibitor (FAPI) has demonstrated promising oncological diagnostic performance. Although no adverse events (AEs) have been previously reported, a formal safety evaluation of FAPI PET/CT is lacking. This study aimed to assess the safety and tolerability of [⁶⁸Ga]Ga‐FAPI‐46 PET/CT, with a focus on hemodynamic parameters, AEs, and patient‐reported discomfort. Materials and Methods: Participants were included from two ongoing prospective diagnostic trials: (1) FAPI PET/CT in ovarian cancer (EU CTIS no. 2023‐505938‐98‐00) and (2) FAPI PET/CT in gastric and gastroesophageal junction cancer (EU CTIS no. 2023‐505916‐40‐01). A dose of 150–250 MBq [⁶⁸Ga]Ga‐FAPI‐46 was administered, and low‐dose, non‐contrast CT was performed. Hemodynamic parameters, including systolic and diastolic blood pressure (BP) and heart rate (HR), were measured at baseline, 1‐min post‐injection (p.i.), 10 min p.i., and post‐scan. Additionally, potential AEs and discomfort were assessed at these timepoints and 1 day p.i., and participants were instructed to report events. AEs were graded according to the Common Terminology Criteria for Adverse Events version 5.0. Results: Thirty participants were included. No patient reported AEs or discomfort attributable to [⁶⁸Ga]Ga‐FAPI‐46, and no significant changes in mean systolic or diastolic BP were observed; however, three patients experienced increases in systolic BP classified as AEs. A clinically non‐relevant but statistically significant ( p < 0.01) decrease in HR (from 77 bpm at baseline to 73 bpm at post‐scan) was observed. Conclusion: [⁶⁸Ga]Ga‐FAPI‐46 PET/CT is well tolerated with no immediate patient‐reported discomfort or clinically relevant hemodynamic AEs. The observed decrease in HR from baseline to post‐scan likely reflects prescan nervousness.

Digestive neuroendocrine carcinomas (NEC) are rare, aggressive, and treatment‐resistant malignancies. Platinum and etoposide are recommended as first line treatment; however, with limited benefit in colorectal NEC and in NEC with low Ki67 of 20%–55%. There is no firm evidence for second‐line treatment. Being efficient in digestive adenocarcinomas, FOLFIRINOX is sometimes used also in patients with NEC. In this retrospective cohort study, patients with digestive NEC who received FOLFIRINOX and were diagnosed 2014–2021 were retrospectively identified at three Scandinavian centers. Histology was re‐evaluated according to the 2019 WHO classification to exclude NET G3 tumors. Patient characteristics, treatment response, and survival outcomes were assessed. Fifty cases were identified; four of these were classified as mixed neuroendocrine non‐neuroendocrine neoplasm (MiNEN). The most common primary sites were colon ( n = 17) and pancreas ( n = 13). FOLFIRINOX was administrated predominantly in later lines (82%). Overall response rate (RR) was 44% (95% confidence interval (CI): 29%–58%) and disease control rate 72% (CI: 57%–83%), while median progression free survival was 5.6 months (CI: 4.3–6.9 months). Twenty‐three patients with colorectal primary, 12 patients with Ki67 < 55%, and 33 patients previously exposed to platinum and etoposide as first line; the RR was 52%, 50%, and 39%, respectively. This study suggests a role for FOLFIRINOX in digestive NEC. High efficacy was observed, even in patients with hard‐to‐treat colorectal primaries, in those with Ki67 < 55%, and in patients previously exposed to platinum and etoposide.

Background: About 40% of patients with pancreatic cancer (PC) are left untreated. Identification of the modifiable factors for opting out could increase the number eligible for treatment. Methods: We first assessed the completeness of registration. Next, we identified patients residing in the North Denmark Region, included 2023/24 in the Danish Pancreas Cancer Database (DPCD), registered as “no treatment”. We supplemented register data with health record data, including reasons for opting out of treatment. Results: Registration in DPCD was complete compared to the National Clinical Cancer Database, except for one patient. Six patients had other tumors. Of a total of 91 patients, 79% were >75 years old, 2/3 were in performance status (PS) > 2, more than half were socially or physically fragile, while 42% had significant comorbidity. Only 20% were referred to an oncologist. The median overall survival was 2 months, and the 1-year survival was 6%. Clinical stage and PS were prognostic in multivariable analysis. In 70%, poor PS was a reason for opting out of treatment, while 11% declined treatment without objective reasons. Conclusions: Poor PS, frailty, or patients’ wishes explained 89% opting out of treatment. On a patient level, modifiable factors seem limited in this population.

There is limited data regarding the rare and aggressive colorectal neuroendocrine carcinoma (CR‐NEC). In this large prospective study, molecular–clinical characteristics and treatment outcomes following palliative chemotherapy are reported for 163 metastatic CR‐NEC patients, with a comparison to a population‐based prospective cohort of 263 metastatic colorectal adenocarcinoma (CR‐AC) patients. Eighty‐three percent of CR‐NEC received first‐line platinum‐etoposide, while 98% of CR‐AC patients received first‐line fluorouracil‐based chemotherapy. Disease control rate across all first‐line regimens in CR‐NEC and CR‐AC was 43% vs. 74%, immediate progressive disease 46% vs. 15%, progression‐free survival 2.4 months (m) (95% CI 2.1–3.3) vs. 7.7 m (95% CI 6.9–8.5), and overall survival 6.7 m (95% CI 5.6–8.8) vs. 16.8 m (95% CI 13.7–20.3), all, p < .001. CR‐NEC more often had synchronous metastases, worse performance status, and symptom burden at treatment initiation than CR‐AC (all, p < .001). Two‐year survival was 9% vs. 37% in CR‐NEC and CR‐AC ( p < .001). BRAF mutations were frequent in CR‐NEC and CR‐AC (26% vs. 20%, p = .153) and associated with shorter OS in CR‐NEC and CR‐AC ( p = .025 and p = .003). KRAS mutations were less frequent in CR‐NEC than CR‐AC (34% vs. 45%, p = .041), but only associated with shorter OS in rectal NEC ( p = .04). The frequencies of APC and TP53 mutations were similar between the cohorts and did not impact survival. Metastatic CR‐NEC and CR‐AC are clinically distinct, with NEC demonstrating more aggressive features, limited treatment effect, and worse prognosis. Although they share important driver mutations, the underlying reason for their marked clinical differences remains unclear.

Background: Evidence of treatment of patients with relapse following multimodal treatment for oesophageal, gastro-oesophageal junctional and gastric adenocarcinoma is almost absent. Methods: In a nationwide consecutive cohort of 202 patients, radically resected after perioperative chemotherapy (CTx) and followed-up without scheduled imaging, we identified 89 patients with recurrence within 12 years. We registered prior clinico-pathological and treatment characteristics, alarming symptoms, work-up, recurrence patterns, treatment of recurrence, and outcome. Results: Median time to recurrence was 15.2 months, 91% of relapses occurred within 3 years. Frequent alarming symptoms were pain, weight loss and loss of appetite. Fifty-four percent recurred at multiple sites, 36% at a single anatomic site, and 10% were solitary. Recurrence was a 99% fatal event with a median overall survival (OS) of only 4.6 months. Older age, ypN3 at surgery, poor performance status, weight loss, non-solitary recurrence, no postoperative CTx, and no palliative CTx, were associated with short OS. Three patients had initial surgery, but all progressed; one additional patient was cured by salvage surgery after palliative CTx. Sixty percent (53 patients) were treated with CTx yielding a median progression-free survival and OS of 4.0 and 5.8 months, respectively; the overall response rate was 35%. Pleuroperitoneal metastases predicted poor prognosis. Non-platinum-based, first-line palliative CTx was used in 38%, mostly in patients with short treatment-free interval. Interpretation: In this national cohort, recurrence was a 99% fatal event and only 60% of patients received palliative CTx. Efficacy of palliative CTx at relapse after multi-modal treatment is poor and needs further investigations.

Description of the quality control of DNA extraction

Multivariate Cox proportional hazards model of progression free survival by ctDNA response.

Overall survival according to baseline ctDNA status