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Background and purpose: Squamous cell carcinoma of the anus (SCCA) can recur after chemoradiotherapy (CRT). Early prediction of treatment response is crucial for individualising treatment. Existing data on radiological biomarkers is limited and contradictory. We performed an individual patient data meta-analysis (IPM) of four prospective trials investigating whether diffusion-weighted (DW) magnetic resonance imaging (MRI) in weeks two to three of CRT predicts treatment failure in SCCA. Material and methods: Individual patient data from four trials, including paired DW-MRI at baseline and during CRT, were combined into one dataset. The association between ADC volume histogram parameters and treatment failure (locoregional and any failure) was assessed using logistic regression. Pre-defined analysis included categorising patients into a change in the mean ADC of the delineated tumour volume above and below 20%. Results: The study found that among all included 142 patients, 11.3 % (n = 16) had a locoregional treatment failure. An ADC mean change of 20 % resulted in a locoregional failure rate of 16.7 % and 8.0 %, respectively. However, no other ADC-based histogram parameter was associated with locoregional or any treatment failure. Conclusions: DW-MRI standard parameters, as an isolated biomarker, were not found to be associated with increased odds of treatment failure in SCCA in this IPM. Radiological biomarker investigations involve multiple steps and can result in heterogeneous data. In future, it is crucial to include radiological biomarkers in large prospective trials to minimize heterogeneity and maximize learning.

Abstract Background Small cell lung cancer (SCLC) is an aggressive cancer often presenting in an advanced stage and prognosis is poor. Early response evaluation may have impact on the treatment strategy. Aim We evaluated 18F-fluorothymidine-(FLT)-PET/diffusion-weighted-(DW)-MRI early after treatment start to describe biological changes during therapy, the potential of early response evaluation, and the added value of FLT-PET/DW-MRI. Methods Patients with SCLC referred for standard chemotherapy were eligible. FLT-PET/DW-MRI of the chest and brain was acquired within 14 days after treatment start. FLT-PET/DW-MRI was compared with pretreatment FDG-PET/CT. Standardized uptake value (SUV), apparent diffusion coefficient (ADC), and functional tumor volumes were measured. FDG-SUVpeak, FLT-SUVpeak, and ADCmedian; spatial distribution of aggressive areas; and voxel-by-voxel analyses were evaluated to compare the biological information derived from the three functional imaging modalities. FDG-SUVpeak, FLT-SUVpeak, and ADCmedian were also analyzed for ability to predict final treatment response. Results Twelve patients with SCLC completed FLT-PET/MRI 1–9 days after treatment start. In nine patients, pretreatment FDG-PET/CT was available for comparison. A total of 16 T-sites and 12 N-sites were identified. No brain metastases were detected. FDG-SUVpeak was 2.0–22.7 in T-sites and 5.5–17.3 in N-sites. FLT-SUVpeak was 0.6–11.5 in T-sites and 1.2–2.4 in N-sites. ADCmedian was 0.76–1.74 × 10− 3 mm2/s in T-sites and 0.88–2.09 × 10−3 mm2/s in N-sites. FLT-SUVpeak correlated with FDG-SUVpeak, and voxel-by-voxel correlation was positive, though the hottest regions were dissimilarly distributed in FLT-PET compared to FDG-PET. FLT-SUVpeak was not correlated with ADCmedian, and voxel-by-voxel analyses and spatial distribution of aggressive areas varied with no systematic relation. LT-SUVpeak was significantly lower in responding lesions than non-responding lesions (mean FLT-SUVpeak in T-sites: 1.5 vs. 5.7; p = 0.007, mean FLT-SUVpeak in N-sites: 1.6 vs. 2.2; p = 0.013). Conclusions FLT-PET and DW-MRI performed early after treatment start may add biological information in patients with SCLC. Proliferation early after treatment start measured by FLT-PET is a promising predictor for final treatment response that warrants further investigation. Trial registration Clinicaltrials.gov, NCT02995902. Registered 11 December 2014 - Retrospectively registered.

Angiogenesis is crucial in tissue repair and prevents scar tissue formation following an ischemic event such as myocardial infarction. The ischemia induces formation of new capillaries, which have high expression of integrin αvβ3. [68Ga]Ga-NODAGA-E[(cRGDyK)]2 ([68Ga]Ga-RGD) is a promising PET-radiotracer reflecting angiogenesis by binding to integrin αvβ3. A Göttingen mini-pig underwent transient catheter-induced left anterior descending artery (LAD) occlusion for 120 min, and after 8 weeks was imaged on a Siemens mMR 3T PET/MR system. A large antero-septal infarction was evident by late gadolinium enhancement (LGE) on the short axis and 2–4 chamber views. The infarcted area corresponded to the area with high [68Ga]Ga-RGD uptake on the fused PET/MR images, with no uptake in the healthy myocardium. To support the hypothesis that [68Ga]Ga-RGD uptake reflects angiogenesis, biopsies were sampled from the infarct border and healthy myocardium. Expression of αvβ3 was evaluated using immunohistochemistry. The staining showed higher αvβ3 expression in the capillaries of the infarct border compared to those in the healthy myocardium. These initial data confirm in vivo detection of angiogenesis using [68Ga]Ga-RGD PET in a translational model, which overall support the method applicability when evaluating novel cardio-protective therapies.

Background and study aims Electrochemotherapy is an anticancer treatment that uses electric pulses to facilitate uptake of chemotherapeutic drugs in tumor cells and has proven to have a high local cytotoxic effect with minimal adverse events. Electrochemotherapy has mostly been used in treatment of cutaneous metastases but development of a new endoscopic electrode device has made treatment of colorectal tumors possible. This first-in-man multicenter phase I study investigated safety and efficacy of electrochemotherapy using endoscopic electroporation in patients with colorectal tumors. Patients and methods Seven patients with colorectal tumors who were deemed ineligible for or had declined standard treatment were included. They were treated with bleomycin either intratumorally or intravenously and the electric pulses were delivered through the endoscopic electrode device. Safety and efficacy were assessed clinically and by scans immediately after treatment and adverse events were reported. Response was evaluated up to 6 months after treatment by scans (magnetic resonance imaging or computed tomography) and endoscopic examinations. Results Seven patients aged 62 to 88 years with multiple comorbidities were included and had one or two treatments each. Post-treatment scans showed tumor responses in the treated areas and no damage to surrounding tissues. Only a few grade one adverse events were reported. Three patients had preoperative rectal bleeding, of which two reported cessation of bleeding and one reported decreased bleeding. Conclusion This first-in-man study shows that electrochemotherapy for colorectal tumors using the endoscopic electrode device can induce local tumor response and is safe also for fragile elderly patients with comorbidities.

Eosinophilic cystitis (EC) is a relatively rare, but benign inflammatory bladder disease compared to that of the malignant pediatric rhabdomyosarcoma (RMS), in which it can be mimicking on initial suspicion. The origin, symptoms and findings of both EC and RMS are still discussed and hence, lead to the challenge in distinguishing them by cystoscopy and several image modalities. We present a case in which cross-sectional imaging modalities including fluorine-18-fluro-2-deoxy-D-glucose (18F-FDG)-positron emission tomography (PET) / computed tomography (CT) / magnetic resonance imaging (MRI) (18F-FDG-PET/CT/MRI (The imaging modality 18F-FDG-PET/CT/MRI referring to two continuous scans scanned on the same 18F-FDG-tracer dose for both the whole-body 18F-FDG-PET/CT and the regional 18F-FDG-PET/MRI of the pelvis.)) raised suspicion of RMS. Hence, the final diagnosis of EC was established by repeated histopathology. It is important to have EC in mind when seeking differential diagnosis of malignant diseases like RMS in order to provide the correct treatment for the patient and highly homogenously increased 18F-FDG-uptake should raise the suspicion of EC as a differential diagnosis. Furthermore, 18F-FDG-uptake rate is suggested as a future potential biomarker for monitoring of therapeutic response in eosinophilic inflammatory diseases, thus more research on this topic is needed.

Background and study aims Esophageal cancer is on the rise in the western world and the disease has a poor 5-year survival prognosis below 20 %. Electrochemotherapy is a treatment where a chemotherapeutic drug is combined with locally applied electrical pulses, in order to increase the drug’s cytotoxicity in malignant cells. This study presents the first results with electrochemotherapy treatment in esophageal cancer. Patients and methods In this first-in-human trial, six patients with advanced esophageal cancer were treated with electrochemotherapy using intravenous bleomycin. All side effects and adverse events (AEs) were registered and the patients were later evaluated with gastroscopy and 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI). Results Treatment were well tolerated, main AEs being nausea, vomiting, oral thrush, pneumonia, retrosternal pain, fever, and hoarseness. No serious complications were observed. Five patients had a visual tumor response confirmed by gastroscopy. In two cases, these findings were confirmed with 18F-FDG PET/MRI as it revealed a reduction of total tumor mass. Conclusion Electrochemotherapy in patients with advanced esophageal cancer was conducted without major safety concerns. This study paves the way for larger studies, which may further elucidate response rates for and side effects of this new treatment.

Purpose: With the increasing number of therapy options available for patients with lung cancer, early response evaluation is needed. We performed this pilot study to assess the feasibility of early, repeated Positron emission tomography-magnetic resonance (PET/MR), the impact of timing and the capability for response prediction in lung tumors during chemotherapy. Methods: Patients with stage IV non-small cell lung cancer referred for chemotherapy were prospectively recruited. Fluorine-18-Fluorodeoxyglucose(18F-FDG)-PET/MR scans were performed prior to, during and after the first or second cycle of chemotherapy. Primary tumors were defined on all scans and size, FDG-uptake and apparent diffusion coefficient (ADC) were measured. Early response was described over time and a Standard Linear Mixed Model was applied to analyze changes over time. Results: 45 FDG-PET/MR scans were performed in 11 patients. Whereas the overall changes measured by ADC did not change significantly, there was an overall significant decrease in FDG-uptake from pre to post treatment scans. There was no difference in the FDG-uptake measured 1 or 3 weeks after therapy, but uptake measured 2 weeks after therapy differed from measurements at week 3. Changes measured in patients scanned during the first treatment cycle appeared more pronounced than during the second cycle. Conclusions: This pilot study indicates that response evaluation shortly after initiation of chemotherapy appears concordant with later evaluation and probably more reliable than evaluation midway between cycles. Responses during or after the first cycle of chemotherapy rather than during subsequent cycles are likely to be more readily measured.