BACKGROUND: Rubidium-82 positron emission tomography ( ⁸² Rb PET) myocardial perfusion imaging is used in clinical practice to quantify regional perfusion defects. Additionally, ⁸² Rb PET provides a measure of absolute myocardial flow reserve (MFR), describing the vasculature state of health. We assessed whether ⁸² Rb PET-derived MFR is associated with all-cause mortality independently of the extent of perfusion defects. METHODS: We conducted a multicenter clinical registry-based study of patients undergoing ⁸² Rb PET myocardial perfusion imaging on suspicion of chronic coronary syndromes. Patients were followed up in national registries for the primary outcome of all-cause mortality. Global MFR ≤2 was considered reduced. RESULTS: Among 7169 patients studied, 38.1% were women, the median age was 69 (IQR, 61–76) years, and 39.0% had MFR ≤2. A total of 667 (9.3%) patients died during a median follow-up of 3.1 (IQR, 2.6–4.0) years, more in patients with MFR ≤2 versus MFR >2 (15.7% versus 5.2%; P <0.001). MFR ≤2 was associated with all-cause mortality across subgroups defined by the extent of perfusion defects (all P <0.05). In a Cox survival regression model adjusting for sex, age, comorbidities, kidney function, left ventricular ejection fraction, and perfusion defects, MFR ≤2 was a robust predictor of mortality with a hazard ratio of 1.62 (95% CI, 1.31–2.02; P <0.001). Among patients with no reversible perfusion defects (n=3101), MFR ≤2 remained strongly associated with mortality (hazard ratio, 1.86 [95% CI, 1.26–2.73]; P <0.01). The prognostic value of impaired MFR was similar for cardiac and noncardiac death. CONCLUSIONS: MFR ≤2 predicts all-cause mortality independently of the extent of perfusion defects. Our results support the inclusion of MFR when assessing the prognosis of patients suspected of chronic coronary syndromes.

Circulating tumor DNA (ctDNA) has the potential to become a reliable biomarker for identifying minimal residual disease (MRD) and predicting recurrence in patients with non-small cell lung cancer (NSCLC) following curative treatment. However, there is a lack of studies that investigate the clinical validity of ctDNA using a tumor-agnostic approach, which can provide significant clinical benefits. We analyzed samples from 45 NSCLC patients recruited in a prospective national multicenter study, all of whom had undergone curative treatment. A total of 38 pre-treatment plasma samples and 76 post-treatment plasma samples were examined using a commercially available cancer personalized profiling by deep sequencing (CAPP-seq) strategy, and a tumor-agnostic approach. Post-treatment samples were collected at two distinct landmark time points: Follow-up 1 (0.5-4.5 months post-treatment) and Follow-up 2 (4.5-7.5 months post-treatment). Detectable ctDNA post-treatment was significantly associated with increased risk of tumor recurrence and shorter recurrence-free survival (RFS). Using only a single blood sample taken from Follow-up 2, we correctly identified MRD in 50% of the patients who later experienced recurrence. However, subgroup analysis further revealed that in patients treated with radiotherapy or chemoradiotherapy (CRT), ctDNA detection was significantly linked to shorter RFS in the MRD analysis from Follow-up 2, but not in the MRD analysis from Follow-up 1. These findings suggest that post-treatment ctDNA, detected using a tumor-agnostic approach, is a reliable biomarker for predicting recurrence in NSCLC patients following curative treatment. However, the optimal timing for blood sampling to detect MRD appears to depend on the type of curative treatment received.

Immune checkpoint inhibitor therapy (ICT) is a new treatment strategy developed for the treatment of cancer. ICT inhibits pathways known to downregulate the innate immune response to cancer cells. These drugs have been shown to be effective in the treatment of a variety of cancers, including metastatic melanoma and lung cancer. Challenges in response evaluation of patients in ICT have risen as immune related side effects and immune cell infiltration may be confused with progressive disease. Furthermore, the timing of the evaluation scan may be challenged by relatively slow responses. To overcome this, new response criteria for evaluating these patients with morphologic imaging have been proposed. The aim of this paper is to review and discuss the current evidence for the use of molecular imaging, e.g., PET/CT (Positron Emission Tomography/Computer Tomography) with ¹⁸F-Fluorodeoxyglucoes (FDG) as an alternative imaging method for monitoring patients undergoing ICT. Following the currently available evidence, this review will primarily focus on patients with malignant melanoma.

Despite increased focus on prevention as well as improved treatment possibilities, lung cancer remains among the most frequent and deadliest cancer diagnoses worldwide. Even lung cancer patients treated with curative intent have a high risk of relapse, leading to a dismal prognosis. More knowledge on the efficacy of surveillance with both current and new technologies as well as on the impact on patient treatment, quality of life, and survival are urgently needed. We therefore designed a randomized phase 3 trial. In one arm, every other computed tomography (CT) scan is replaced by positron emission tomography/CT, the other arm is the standard follow-up scheme with CT. The standard arm is identical to the current national Danish follow-up program. The primary endpoint is to compare the number of relapses treatable with curative intent in the 2 arms. We aim to include 750 patients over a 3-year period. Additionally, we will test the feasibility of noninvasive lung cancer diagnostics and surveillance in the form of circulating tumor DNA analysis. For this purpose, blood samples are collected before treatment and at each following control. The blood samples are stored in a biobank for later analysis and will not be used for guiding patient treatment decisions.

Post-treatment surveillance is recommended for non-small cell lung cancer (NSCLC) due to a high risk of recurrence, but evidence on the optimal surveillance method is lacking. This trial evaluates fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([¹⁸F]FDG PET/CT) versus contrast-enhanced CT (ceCT) for surveillance in NSCLC patients. In this multicenter, randomized controlled trial (SUPE_R, ClinicalTrials.gov NCT03740126), patients with stage IA-IIIC NSCLC were randomized 1:1 to standard surveillance (ceCT) or surveillance with [¹⁸F]FDG PET/CT after completion of curative treatment. The primary outcome was the proportion of recurrences treated with curative intent. Secondary outcomes included time to recurrence (TTR) and overall survival (OS). Between February 2019 and February 2022, 750 patients were randomized to PET/CT (n=373) or CT (n=377). Recurrences occurred in 164 patients (22%). The proportion of recurrences treated with curative intent was identical between the PET group (42 of 87) and CT group (37 of 77), both 48% (p=0.98). More recurrences were detected through scheduled follow-up in the PET group (90%) compared to the CT group (77%; p = 0.02). There were no significant differences in TTR (HR 1.12, 95% CI 0.82 - 1.52, p = 0.48) or OS (HR 0.97, 95% CI 0.66 - 1.43, p = 0.89) between groups. Surveillance with [¹⁸F]FDG PET/CT did not improve rates of curatively treated recurrences, TTR, or OS compared to ceCT in NSCLC patients after curative treatment. These findings do not support the routine use of [¹⁸F]FDG PET/CT for post-treatment surveillance in this patient population.

Following curative treatment for non-small cell lung cancer (NSCLC), surveillance to detect recurrence is recommended. While computed tomography (CT) is the current standard for follow-up imaging, the optimal surveillance strategy remains debated. This study compares the diagnostic accuracy of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT; hereafter referred to as PET/CT) and CT for NSCLC surveillance. This study represents a secondary analysis of data from a randomized controlled trial (SUPE_R, ClinicalTrials.gov NCT03740126) of patients with stage IA-IIIC NSCLC who completed curative-intent treatment between February 2019 and February 2022. CT and PET/CT scans were compared for recurrence detection using biopsy, multidisciplinary team assessment, or follow-up imaging as reference standards. The analysis included 899 PET/CT scans and 852 CT scans from 692 patients (mean age 69 years ± 8 [SD]; 412 female). For detecting recurrence, PET/CT demonstrated a higher sensitivity (88% [95% CI, 80%-93%] vs. 62% [95% CI, 50%-73%]; P < .001) but lower specificity (89% [95% CI, 86%-91%] vs. 96% [95% CI, 94%-97%]; P < .001) compared to CT. PET/CT demonstrated a higher sensitivity compared to CT after treatment with chemoradiotherapy (100% [95% CI, 72%-100%] vs. 46% [95% CI, 19%-75%]; P = .006) and at 0 to 6 month after treatment (83% [95% CI, 63%-94%] vs. 41% [95% CI, 21%-65%]; P = .008). The higher sensitivity of PET/CT, particularly after chemoradiotherapy and early post-treatment, suggests it may be particularly valuable in these high-risk scenarios. However, CT remains preferred for routine surveillance of low-risk patients given its superior specificity.