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Objectives To assess the frequency, intensity, and clinical impact of [ 18 F]FDG-avidity of axillary lymph nodes after vaccination with COVID-19 vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) in patients referred for oncological FDG PET/CT. Methods One hundred forty patients referred for FDG PET/CT during February and March 2021 after first or second vaccination with Pfizer-BioNTech or Moderna were retrospectively included. FDG-avidity of ipsilateral axillary lymph nodes was measured and compared. Assuming no knowledge of prior vaccination, metastatic risk was analyzed by two readers and the clinical impact was evaluated. Results FDG PET/CT showed FDG-avid lymph nodes ipsilateral to the vaccine injection in 75/140 (54%) patients with a mean SUV max of 5.1 (range 2.0 – 17.3). FDG-avid lymph nodes were more frequent in patients vaccinated with Moderna than Pfizer-BioNTech (36/50 [72%] vs. 39/90 [43%] cases, p < 0.001). Metastatic risk of unilateral FDG-avid axillary lymph nodes was rated unlikely in 52/140 (37%), potential in 15/140 (11%), and likely in 8/140 (6%) cases. Clinical management was affected in 17/140 (12%) cases. Conclusions FDG-avid axillary lymph nodes are common after COVID-19 vaccination. The avidity of lymph nodes is more frequent in Moderna compared to that in Pfizer-BioNTech vaccines. To avoid relatively frequent clinical dilemmas, we recommend carefully taking the history for prior vaccination in patients undergoing FDG PET/CT and administering the vaccine contralateral to primary cancer. Key Points • PET/CT showed FDG-avid axillary lymph nodes ipsilateral to the vaccine injection site in 54% of 140 oncological patients after COVID-19 vaccination. • FDG-avid lymphadenopathy was observed significantly more frequently in Moderna compared to patients receiving Pfizer-BioNTech-vaccines. • Patients should be screened for prior COVID-19 vaccination before undergoing PET/CT to enable individually tailored recommendations for clinical management.

Background Neoadjuvant chemotherapy (CT) followed by radiotherapy (RT) and surgery showed a median survival of 28.7 months in resectable stage IIIB non-small-cell lung cancer (NSCLC) patients (pts). Here, we evaluate the impact of concomitant cetuximab to the same neoadjuvant chemo-radiotherapy (CRT) in selected patients (pts) with NSCLC, stage IIIB. Methods Resectable stage IIIB NSCLC received three cycles of CT (cisplatin 100 mg/m 2 and docetaxel 85 mg/m 2 d1, q3w) followed by RT (44 Gy in 22 fractions) with concomitant cetuximab (250 mg/m 2 , q1w) and subsequent surgery. The primary endpoint was 1-year progression-free survival (PFS). Results Sixty-nine pts were included in the trial. Fifty-seven (83%) pts underwent surgery, with complete resection (R0) in 42 (74%) and postoperative 30 day mortality of 3.5%. Responses were: 57% after CT-cetuximab and 64% after CRT-cetuximab. One-year PFS was 50%. Median PFS was 12.0 months (95% CI: 9.0–15.6), median OS was 21.3 months, with a 2- and 3-yr survival of 41% and 30%, respectively. Conclusions This is one of the largest prospective phase 2 trial to investigate the role of induction CRT and surgery in resectable stage IIIB disease, and the first adding cetuximab to the neoadjuvant strategy. This trial treatment is feasible with promising response and OS rates, supporting an aggressive approach in selected pts.

Immune checkpoint inhibitor treatment has the potential to prolong survival in non-small cell lung cancer (NSCLC), however, some of the patients develop resistance following initial response. Here, we analyze the immune phenotype of matching tumor samples from a cohort of NSCLC patients showing good initial response to immune checkpoint inhibitors, followed by acquired resistance at later time points. By using imaging mass cytometry and whole exome and RNA sequencing, we detect two patterns of resistance¨: One group of patients is characterized by reduced numbers of tumor-infiltrating CD8 +  T cells and reduced expression of PD-L1 after development of resistance, whereas the other group shows high CD8 +  T cell infiltration and high expression of PD-L1 in addition to markedly elevated expression of other immune-inhibitory molecules. In two cases, we detect downregulation of type I and II IFN pathways following progression to resistance, which could lead to an impaired anti-tumor immune response. This study thus captures the development of immune checkpoint inhibitor resistance as it progresses and deepens our mechanistic understanding of immunotherapy response in NSCLC. Acquired resistance to immune checkpoint inhibitors limits therapeutic success in non-small-cell lung cancer, however, the underpinning immune parameters are largely unknown. Here authors distinguish resistance types based on immune cell infiltration, immune checkpoint molecule and cytokine expression level, using paired samples from patients in the sensitive and in the resistant disease phase.

Background Carcinoid heart disease is a rare disease which develops in patients with functional neuroendocrine tumors in an advanced tumor state. Patients diagnosed with carcinoid heart disease have a poor longtime prognosis with respect to morbidity and mortality and long-term data on patient outcomes are lacking. Methods and results In this retrospective study, we analyzed outcomes of 23 patients with carcinoid heart disease enrolled into the SwissNet database. We observed that early diagnosis with echocardiographic surveillance of carcinoid heart disease during the course of the neuroendocrine tumor disease was beneficial to overall survival of patients. Conclusion Through nationwide patient enrollment, the SwissNet registry is a powerful data tool to identify, follow-up and evaluate long-term patient outcomes in patients with rare neuroendocrine tumor driven pathologies including carcinoid heart syndrome with observational methods enabling better therapy optimization to improve patient`s long-term perspectives and survival. In line with the current ESMO recommendations, our data proposes that heart echocardiography should be included as part of the general physical assessment in patients with newly diagnosed NET. Highlights CHD is associated with poor prognosis Early CHD detection prolongs survival Echo as baseline prior NET therapy is recommended

Background The existence of abscopal effects has been suggested already a long time ago, but only recently with the advent of immune checkpoint inhibition in clinical oncology and modern imaging techniques has it become possible to directly observe such effects in patients. They have been well described in patients with malignant melanoma being treated with immune-checkpoint inhibitors and stereotactic radiotherapy, but experience in other malignancies is very limited. Case presentation Here, we describe a case of a patient with metastatic non-small cell lung cancer, who experienced a complete response secondary to an abscopal effect on treatment with anti-PD-1 therapy and stereotactic body radiotherapy to some of the involved sites. Conclusions Our case reports confirms the existence of abscopal effects in NSCLC and suggests synergism between immune-checkpoint inhibition and local ablative RT. We suggest that this approach is now further studied in prospective clinical trials on oligo-metastatic or oligo-progressing NSCLC.

To evaluate whether a machine learning classifier can evaluate image quality of maximum intensity projection (MIP) images from F18-FDG-PET scans. A total of 400 MIP images from F18-FDG-PET with simulated decreasing acquisition time (120 s, 90 s, 60 s, 30 s and 15 s per bed-position) using block sequential regularized expectation maximization (BSREM) with a beta-value of 450 and 600 were created. A machine learning classifier was fed with 283 images rated “sufficient image quality” and 117 images rated “insufficient image quality”. The classification performance of the machine learning classifier was assessed by calculating sensitivity, specificity, and area under the receiver operating characteristics curve (AUC) using reader-based classification as the target. Classification performance of the machine learning classifier was AUC 0.978 for BSREM beta 450 and 0.967 for BSREM beta 600. The algorithm showed a sensitivity of 89% and 94% and a specificity of 94% and 94% for the reconstruction BSREM 450 and 600, respectively. Automated assessment of image quality from F18-FDG-PET images using a machine learning classifier provides equivalent performance to manual assessment by experienced radiologists.

This study aimed to evaluate the diagnostic accuracy of Node Reporting and Data System (Node-RADS) in discriminating between normal, reactive, and metastatic axillary LNs in patients with melanoma who underwent SARS-CoV-2 vaccination. Patients with proven melanoma who underwent a 2-[ 18 F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (2-[ 18 F]-FDG PET/CT) between February and April 2021 were included in this retrospective study. Primary melanoma site, vaccination status, injection site, and 2-[ 18 F]-FDG PET/CT were used to classify axillary LNs into normal, inflammatory, and metastatic (combined classification). An adapted Node-RADS classification (A-Node-RADS) was generated based on LN anatomical characteristics on low-dose CT images and compared to the combined classification. 108 patients were included in the study (54 vaccinated). HALNs were detected in 42 patients (32.8%), of whom 97.6% were vaccinated. 172 LNs were classified as normal, 30 as inflammatory, and 14 as metastatic using the combined classification. 152, 22, 29, 12, and 1 LNs were classified A-Node-RADS 1, 2, 3, 4, and 5, respectively. Hence, 174, 29, and 13 LNs were deemed benign, equivocal, and metastatic. The concordance between the classifications was very good (Cohen’s k : 0.91, CI 0.86–0.95; p -value < 0.0001). A-Node-RADS can assist the classification of axillary LNs in melanoma patients who underwent 2-[ 18 F]-FDG PET/CT and SARS-CoV-2 vaccination.

Background Systemic response to local anticancer treatment is a phenomenon called ‘abscopal effect’. The immune system is thought to play a pivotal role in its occurrence. To date, several cases have been reported, particularly in patients receiving combined local treatment and immune checkpoint inhibitors. In such cases, it is impossible to discriminate between the effects of local and systemic treatment. Only a few cases of abscopal effect have been described with radiotherapy alone. Case presentation Here, we report on the case of an 81-year-old woman with recurrent metastatic squamous cell carcinoma of the lung with mediastinal tumor bulk, lymph node and bone metastases. The patient refused to undergo systemic treatment, and palliative stereotactic radiotherapy of the mediastinal tumor was performed. At restaging with FDG-PET/CT, the patient presented with a decrease in size and FDG-avidity both of the irradiated site and of the lymph node and bone metastases (which did not receive radiotherapy). At 25 months after radiotherapy, the patient is still in remission at all sites. Conclusions This is a rare case of an abscopal effect after radiotherapy as monotherapy. It is one of the few hitherto reported for lung cancer. Several ongoing studies with a combination of radiotherapy and immunotherapy are seeking to exploit a potential synergy to induce abscopal effects.

Background Malignant serous effusion (MSE) denotes a manifestation of metastatic disease with typical high concentrations of both cancer and immune cells, making them an ideal resource for in vitro cytologic studies. Hence, the aim of the study was to investigate the features of 2D and 3D MSE culture systems as well as their feasibilities for in vitro drug screening. Methods Pleural and peritoneal effusions from 8 patients were collected and processed for 2D monolayer and 3D hanging drop cell culture into GravityPLUS™ plates. Representative markers for cell components, proliferation rate and tumour classification were investigated by immunohistochemistry, followed by absolute quantification using a digitalised image analysis approach. Further, we implemented another 3D cell culture model based on a low attachment method for in vitro drug sensitivity testing of carboplatin, pemetrexed and pembrolizumab for 5 patients. Results Monolayer cell culture was favourable for the growth of mesothelial cells, while hanging drop culture in GravityPLUS™ plates showed better ability for preserving cancer cells, inducing positive diagnostic markers expression and restraining the growth of mesothelial cells. For in vitro drug testing, MSE from five patients presented various drug sensitivities, and one case showed strong response to PD-1 checkpoint inhibition (pembrolizumab). For some patients, the application of combinatorial drugs had better therapeutic responses compared to monotherapy. Conclusions Digitalised quantification of data offers a better understanding of different MSE culture models. More importantly, the proposed platforms are practical and amenable for performing in vitro chemo-/immunotherapeutic drug testing by using routine cytologic MSE in a personalised manner. Next to cell blocks, our work demonstrates the prognostic and predictive value of cytologic effusion samples.

Background In patients with resectable stage III non-small cell lung cancer (NSCLC), induction chemoimmunotherapy followed by surgical resection has shown unprecedented rates of pathological response and event-free survival. However, a triple-induction including radiochemotherapy and immunotherapy followed by surgical resection has not been routinely established in clinical practice. Case presentation We report the case of a 47-year-old patient with stage IIIA NSCLC who was treated in a combined concept including induction concurrent radiochemotherapy, followed by 4 cycles of pembrolizumab and subsequent intrapericardial left-sided pneumonectomy. Histological analysis revealed a pathological complete response. Conclusions The case demonstrates that the combination of neoadjuvant chemo-, radio- and immunotherapy in advanced NSCLC may lead to a relevant down-staging and may enable a R0-resection of a borderline resectable tumor. However, the combination of four different treatment modalities requires resilience and a good performance status. A triple induction treatment may be a promising option for selected patients with locally advanced NSCLC and good performance status.