Body composition impacts outcome of bronchoscopic lung volume reduction in patients with severe emphysema: a fully automated CT-based analysis.

Chronic Obstructive Pulmonary Disease (COPD) is characterized by progressive and irreversible airflow limitation, with individual body composition influencing disease severity. Severe emphysema worsens symptoms through hyperinflation, which can be relieved by bronchoscopic lung volume reduction (BLVR). To investigate how body composition, assessed through CT scans, impacts outcomes in emphysema patients undergoing BLVR. Fully automated CT-based body composition analysis (BCA) was performed in patients with end-stage emphysema receiving BLVR with valves. Post-interventional muscle and adipose tissues were quantified, body size-adjusted, and compared to baseline parameters. Between January 2015 and December 2022, 300 patients with severe emphysema underwent endobronchial valve treatment. Significant improvements were seen in outcome parameters, which were defined as changes in pulmonary function, physical performance, and quality of life (QoL) post-treatment. Muscle volume remained stable (1.632 vs. 1.635 for muscle bone adjusted ratio (BAR) at baseline and after 6 months respectively), while bone adjusted adipose tissue volumes, especially total and pericardial adipose tissue, showed significant increase (2.86 vs. 3.00 and 0.16 vs. 0.17, respectively). Moderate to strong correlations between bone adjusted muscle volume and weaker correlations between adipose tissue volumes and outcome parameters (pulmonary function, QoL and physical performance) were observed. Particularly after 6-month, bone adjusted muscle volume changes positively corresponded to improved outcomes (ΔForced expiratory volume in 1 s [FEV1], r = 0.440; ΔInspiratory vital capacity [IVC], r = 0.397; Δ6Minute walking distance [6MWD], r = 0.509 and ΔCOPD assessment test [CAT], r = -0.324; all p < 0.001). Group stratification by bone adjusted muscle volume changes revealed that groups with substantial muscle gain experienced a greater clinical benefit in pulmonary function improvements, QoL and physical performance (ΔFEV1%, 5.5 vs. 39.5; ΔIVC%, 4.3 vs. 28.4; Δ6MWDm, 14 vs. 110; ΔCATpts, -2 vs. -3.5 for groups with ΔMuscle, BAR% < -10 vs. > 10, respectively). BCA results among patients divided by the minimal clinically important difference for forced expiratory volume of the first second (FEV1) showed significant differences in bone-adjusted muscle and intramuscular adipose tissue (IMAT) volumes and their respective changes after 6 months (ΔMuscle, BAR% -5 vs. 3.4 and ΔIMAT, BAR% -0.62 vs. 0.60 for groups with ΔFEV1 ≤ 100 mL vs > 100 mL). Altered body composition, especially increased muscle volume, is associated with functional improvements in BLVR-treated patients.

Impact of Bronchoscopic Lung Volume Reduction with Valves on the Pulmonary Gas Exchange.

Introduction: Bronchoscopic lung volume reduction (BLVR) with endobronchial valves has been shown to be a safe and effective treatment for patients with severe lung emphysema. Previous studies have reported a benefit in pulmonary function, exercise capacity, and quality of life after BLVR-treatment. The effect of BLVR with valves on the pulmonary gas exchange and its association with clinical outcomes has not been analyzed to date. The primary goal of this study was to investigate the impact of BLVR on the pulmonary gas exchange and the impact of the target lobe selection in patients with discordant target lobes in high-resolution computed tomography (HRCT) scan and perfusion scan on the pulmonary gas exchange and clinical outcomes. Methods: In this single-center study, we retrospectively analyzed pulmonary function tests, 6-min-walk-tests, HRCT scans, perfusion scans, and blood gas analyses in 77 patients over the course of 6 months following BLVR treatment. Results: We observed that complete lobar occlusion with bronchoscopic valves leads to a transient impairment of pulmonary gas exchange. Despite this, an overall positive clinical outcome could be shown in patients treated with endobronchial valves. If the target lobe selection based on HRCT and perfusion scans is discrepant, a selection based on the HRCT scan tends to be associated with a better outcome than a selection based on the perfusion scan. Conclusions: Complete lobar occlusion with bronchoscopic valves leads to a transient impairment of pulmonary gas exchange but nevertheless results in an overall positive clinical outcome.

Early Metabolic Response by PET Predicts Sensitivity to Next-Line Targeted Therapy in EGFR-Mutated Lung Cancer with Unknown Mechanism of Acquired Resistance.

Targeted therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has established the precision oncology paradigm in lung cancer. Most patients with EGFR-mutated lung cancer respond but eventually acquire resistance. Methods: Patients exhibiting the EGFR p.T790M resistance biomarker benefit from sequenced targeted therapy with osimertinib. We hypothesized that metabolic response as detected by 18F-FDG PET after short-course osimertinib identifies additional patients susceptible to sequenced therapy. Results: Fourteen patients with EGFR-mutated lung cancer and resistance to first- or second-generation EGFR TKI testing negatively for EGFR p.T790M were enrolled in a phase II study. Five patients (36%) achieved a metabolic 18F-FDG PET response and continued osimertinib. In those, the median duration of treatment was not reached (95% CI, 24 mo to not estimable), median progression-free survival was 18.7 mo (95% CI, 14.6 mo to not estimable), and median overall survival was 41.5 mo. Conclusion: Connecting theranostic osimertinib treatment with early metabolic response assessment by PET enables early identification of patients with unknown mechanisms of TKI resistance who derive dramatic clinical benefit from sequenced osimertinib. This defines a novel paradigm for personalization of targeted therapies in patients with lung cancer dependent on a tractable driver oncogene.

Neoadjuvant nivolumab with or without relatlimab in resectable non-small-cell lung cancer: a randomized phase 2 trial.

Antibodies targeting the immune checkpoint molecules PD-1, PD-L1 and CTLA-4, administered alone or in combination with chemotherapy, are the standard of care in most patients with metastatic non-small-cell lung cancers. When given before curative surgery, tumor responses and improved event-free survival are achieved. New antibody combinations may be more efficacious and tolerable. In an ongoing, open-label phase 2 study, 60 biomarker-unselected, treatment-naive patients with resectable non-small-cell lung cancer were randomized to receive two preoperative doses of nivolumab (anti-PD-1) with or without relatlimab (anti-LAG-3) antibody therapy. The primary study endpoint was the feasibility of surgery within 43 days, which was met by all patients. Curative resection was achieved in 95% of patients. Secondary endpoints included pathological and radiographic response rates, pathologically complete resection rates, disease-free and overall survival rates, and safety. Major pathological (≤10% viable tumor cells) and objective radiographic responses were achieved in 27% and 10% (nivolumab) and in 30% and 27% (nivolumab and relatlimab) of patients, respectively. In 100% (nivolumab) and 90% (nivolumab and relatlimab) of patients, tumors and lymph nodes were pathologically completely resected. With 12 months median duration of follow-up, disease-free survival and overall survival rates at 12 months were 89% and 93% (nivolumab), and 93% and 100% (nivolumab and relatlimab). Both treatments were safe with grade ≥3 treatment-emergent adverse events reported in 10% and 13% of patients per study arm. Exploratory analyses provided insights into biological processes triggered by preoperative immunotherapy. This study establishes the feasibility and safety of dual targeting of PD-1 and LAG-3 before lung cancer surgery.ClinicalTrials.gov Indentifier: NCT04205552 .

LIONS PREY: A New Logistic Scoring System for the Prediction of Malignant Pulmonary Nodules.

OBJECTIVES: Classifying radiologic pulmonary lesions as malignant is challenging. Scoring systems like the Mayo model lack precision in predicting the probability of malignancy. We developed the logistic scoring system 'LIONS PREY' (Lung lesION Score PREdicts malignancY), which is superior to existing models in its precision in determining the likelihood of malignancy. METHODS: We evaluated all patients that were presented to our multidisciplinary team between January 2013 and December 2020. Availability of pathological results after resection or CT-/EBUS-guided sampling was mandatory for study inclusion. Two groups were formed: Group A (malignant nodule; n = 238) and Group B (benign nodule; n = 148). Initially, 22 potential score parameters were derived from the patients' medical histories. RESULTS: After uni- and multivariate analysis, we identified the following eight parameters that were integrated into a scoring system: (1) age (Group A: 64.5 ± 10.2 years vs. Group B: 61.6 ± 13.8 years; multivariate p-value: 0.054); (2) nodule size (21.8 ± 7.5 mm vs. 18.3 ± 7.9 mm; p = 0.051); (3) spiculation (73.1% vs. 41.9%; p = 0.024); (4) solidity (84.9% vs. 62.8%; p = 0.004); (5) size dynamics (6.4 ± 7.7 mm/3 months vs. 0.2 ± 0.9 mm/3 months; p < 0.0001); (6) smoking history (92.0% vs. 43.9%; p < 0.0001); (7) pack years (35.1 ± 19.1 vs. 21.3 ± 18.8; p = 0.079); and (8) cancer history (34.9% vs. 24.3%; p = 0.052). Our model demonstrated superior precision to that of the Mayo score (p = 0.013) with an overall correct classification of 96.0%, a calibration (observed/expected-ratio) of 1.1, and a discrimination (ROC analysis) of AUC (95% CI) 0.94 (0.92-0.97). CONCLUSIONS: Focusing on essential parameters, LIONS PREY can be easily and reproducibly applied based on computed tomography (CT) scans. Multidisciplinary team members could use it to facilitate decision making. Patients may find it easier to consent to surgery knowing the likelihood of pulmonary malignancy. The LIONS PREY app is available for free on Android and iOS devices.

Diagnostic Accuracy of 68Ga-FAPI Versus 18F-FDG PET in Patients with Various Malignancies.

To assess the diagnostic accuracy of 68Ga-labeled fibroblast activation protein inhibitor (FAPI) and 18F-labeled FDG PET for the detection of various tumors, we performed a head-to-head comparison of both imaging modalities across a range of tumor entities as part of our ongoing 68Ga-FAPI PET observational trial. Methods: The study included 115 patients with 8 tumor entities who received imaging with 68Ga-FAPI for tumor staging or restaging between October 2018 and March 2022. Of those, 103 patients received concomitant imaging with 68Ga-FAPI and 18F-FDG PET and had adequate lesion validation for accuracy analysis. Each scan was evaluated for the detection of primary tumor, lymph nodes, and visceral and bone metastases. True or false positivity and negativity to detected lesions was assigned on the basis of histopathology from biopsies or surgical excision, as well as imaging validation. Results: 68Ga-FAPI PET revealed higher accuracy than 18F-FDG PET in the detection of colorectal cancer (n = 14; per-patient, 85.7% vs. 78.6%; per-region, 95.6% vs. 91.1%) and prostate cancer (n = 22; per-patient, 100% vs. 90.9%; per-region, 96.4% vs. 92.7%). 68Ga-FAPI PET and 18F-FDG PET had comparable per-patient accuracy in detecting breast cancer (n = 16, 100% for both) and head and neck cancers (n = 10, 90% for both modalities). 68Ga-FAPI PET had lower per-patient accuracy than 18F-FDG PET in cancers of the bladder (n = 12, 75% vs. 100%) and kidney (n = 10, 80% vs. 90%), as well as lymphoma (n = 9, 88.9% vs. 100%) and myeloma (n = 10, 80% vs. 90%). Conclusion: 68Ga-FAPI PET demonstrated higher diagnostic accuracy than 18F-FDG PET in the diagnosis of colorectal cancer and prostate cancer, as well as comparable diagnostic performance for cancers of the breast and head and neck. Accuracy and impact on management will be further assessed in an ongoing prospective interventional trial (NCT05160051).

NET-Induced Carcinoid Heart Disease Affecting Both Tricuspid and Aortic Valves Due to Patent Foramen Ovale and Right/Left Shunt: A Multi-imaging Challenge to Nuclear Medicine.

ABSTRACT: Carcinoid heart disease (Hedinger syndrome) is a long-term consequence in hormone-active neuroendocrine tumors with hepatic metastases and carcinoid syndrome. Because of serotonin, excess multiple cardiac and pulmonary symptoms evolve, which are further complicated by a patent foramen ovale due to right-left shunting. We present a 53-year-old man with an ileum-neuroendocrine tumor including gross liver metastases and long-term stable disease who subsequently developed Hedinger syndrome. Initially experiencing progressive dyspnea, he eventually experienced severe hypoxemia due to patent foramen ovale. 99mTc-MAA lung perfusion scintigraphy quantitatively identified the right-left shunting, whereas 68Ga-FAPI-46 PET/CT characterized the typical fibrous heart valve thickening due to serotonin-induced fibroblast proliferative properties.

Oncologic Staging with 68Ga-FAPI PET/CT Demonstrates a Lower Rate of Nonspecific Lymph Node Findings Than 18F-FDG PET/CT.

Nonspecific lymph node uptake on 18F-FDG PET/CT imaging is a significant pitfall for tumor staging. Fibroblast activation protein α expression on cancer-associated fibroblasts and some tumor cells is less sensitive to acute inflammatory stimuli, and fibroblast activation protein-directed PET may overcome this limitation. Methods: Eighteen patients from our prospective observational study underwent 18F-FDG and 68Ga fibroblast activation protein inhibitor (FAPI) PET/CT scans within a median of 2 d (range, 0-22 d). Lymph nodes were assessed on histopathology and compared with SUV measurements. Results: On a per-patient basis, lymph nodes were rated malignant in 10 (56%) versus 7 (39%) patients by 18F-FDG PET/CT versus 68Ga-FAPI PET/CT scans, respectively, with a respective accuracy of 55% versus 94% for true lymph node metastases. Five of 6 (83%) false-positive nodes on the 18F-FDG PET/CT scans were rated true negative by the 68Ga-FAPI PET/CT scans. On a per-lesion basis, tumor detection rates were similar (85/89 lesions, 96%). Conclusion: 68Ga-FAPI PET/CT imaging demonstrated higher accuracy for true nodal involvement and therefore has the potential to replace 18F-FDG PET/CT imaging for cancer staging.

DOTATOC PET/CT imaging of a typical carcinoid tumor in a human ex-vivo perfused lung lobe.

The use of Isolated lung perfusion (ILP), combined with medical imaging modalities such as positron emission tomography-computed tomography (PET/CT), provides real-time visualization of tumors in ventilated and perfused vital lung tissue. This experiment intends to show the feasibility and benefits of using ILP combined with PET/CT imaging. Following lung surgery on a 49-year-old male, his left lower lobectomy specimen, which held a typical carcinoid tumor, was preserved on normothermic ILP. Gallium-68-Edotreotide ([68Ga]-DOTATOC) was administered into the ILP circuit, and dynamic emission data from PET/CT was acquired. ILP was carried out for 120 minutes. Near physiologic gas exchange and glucose metabolism were preserved throughout the experiment. The time activity curves (TAC) of 5 different volumes of interest (VOI) showed notable differences in tracer uptake over time. The peripheral area of the carcinoid exhibited delayed but high somatostatin receptor agonist uptake compared to the surrounding parenchyma and the intrapulmonary artery. However, the central area of the carcinoid showed very low [68Ga]-DOTATOC uptake. This experiment demonstrates the potential of ILP combined with PET/CT for kinetic modeling in experimental nuclear medicine imaging. By providing visualization of tracer uptake in perfused lung tissue, this model could potentially improve our understanding of tumor physiology and molecular imaging.

Accuracy of nodal staging by 18F-FDG-PET/CT in limited disease small-cell lung cancer.

BACKGROUND: Small-cell lung cancer (SCLC) is highly aggressive with a nearly incurable disease in most cases. The most important prognostic factor is the status of the mediastinal lymph nodes. Only a small proportion of patients can be diagnosed at early stages and directed to curative multimodal treatment. Therefore, accuracy of nodal staging by (18F)-Fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) computed tomography (18F-FDG-PET/CT) in (very) limited disease SCLC, although not well investigated, is highly important. METHODS: Treatment naive, non-bulky patients treated or diagnosed with SCLC between June 2012 and April 2020 with complete data including FDG-PET/CT and invasive mediastinal staging were retrospectively analyzed (n = 19). Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and accuracy of mediastinal lymph node staging of 18F-FDG-PET/CT was calculated. RESULTS: The FDG-PET/CT showed a sensitivity of 91%, and the specificity was calculated as 87.5%. In this cohort, the disease prevalence in lymph nodes was 58% (n = 11). Positive predictive value was 91%, NPV 88% and accuracy calculated at 89%. One patient was upstaged from single-level N2 to multilevel N2. In one patient, upstaging in invasive staging was performed from N2 to N3, and one patient was downstaged from N1 to N0. CONCLUSIONS: FDG-PET/CT is a valuable tool for the detection of distant metastases, but in mediastinal staging of SCLC some limitations might remain. Invasive methods remain the gold standard. Therefore, the mediastinal lymph nodal status of patients with SCLC screened for multimodal treatment should be further evaluated by additional invasive techniques to verify the exact N-staging and to optimize treatment stratification.

68Ga-SSO-120 PET for Initial Staging of Small Cell Lung Cancer Patients: A Single-Center Retrospective Study.

PET imaging using the somatostatin receptor 2 (SSTR2) antagonist satoreotide trizoxetan (SSO-120, previously OPS-202) could offer accurate tumor detection and screening for SSTR2-antagonist radionuclide therapy in patients with SSTR2-expressing small cell lung cancer (SCLC). The aim of this single-center study was to investigate tumor uptake and detection rates of 68Ga-SSO-120 in comparison to 18F-FDG PET in the initial staging of SCLC patients. Methods: Patients with newly diagnosed SCLC who underwent additional whole-body 68Ga-SSO-120 PET/CT during the initial diagnostic workup were retrospectively included. The mean administered activity was 139 MBq, and the mean uptake time was 60 min. Gold-standard staging 18F-FDG PET/CT was evaluated if available within 2 wk before or after 68Ga-SSO-120 PET if morphologic differences in CT images were absent. 68Ga-SSO-120- or 18F-FDG-positive lesions were reported in 7 anatomic regions (primary tumor, thoracic lymph node metastases, and distant metastases including pleural, contralateral pulmonary, liver, bone, and other) according to the TNM classification for lung cancer (eighth edition). Consensus TNM staging (derived from CT, endobronchial ultrasound-guided transbronchial needle aspiration, PET, and brain MRI) by a clinical tumor board served as the reference standard. Results: Thirty-one patients were included, 12 with limited and 19 with extensive disease according to the Veterans Administration Lung Study Group classification. 68Ga-SSO-120-positive tumor was detected in all patients (100%) and in 90 of the 217 evaluated regions (41.5%). Thirteen patients (42.0%) had intense average 68Ga-SSO-120 uptake (region-based mean SUVmax ≥ 10); 28 patients (90.3%) had average 68Ga-SSO-120 uptake greater than liver uptake (region-based mean peak tumor-to-liver ratio > 1). In 25 patients with evaluable 18F-FDG PET, primary tumor, thoracic lymph node metastases, and distant metastases were detected in 100%, 92%, and 64%, respectively, of all investigated patients by 68Ga-SSO-120 and in 100%, 92%, and 56%, respectively, by 18F-FDG PET. 68Ga-SSO-120 PET detected additional contralateral lymph node, liver, and brain metastases in 1, 1, and 2 patients, respectively (no histopathology available), and 18F-FDG PET detected additional contralateral lymph node metastases in 3 patients (1 confirmed, 1 systematic endobronchial ultrasound-guided transbronchial needle aspiration-negative, and 1 without available histopathology). None of these differences altered Veterans Administration Lung Study Group staging. The region-based monotonic correlation between 68Ga-SSO-120 and 18F-FDG uptake was low (Spearman ρ = 0.26-0.33). Conclusion: 68Ga-SSO-120 PET offers high diagnostic precision with comparable detection rates and additional complementary information to the gold standard, 18F-FDG PET. Consistent uptake in most patients warrants exploration of SSTR2-directed radionuclide therapy.

Preoperative PET-SUVmax and volume based PET parameters of the primary tumor fail to predict nodal upstaging in early-stage lung cancer.

OBJECTIVES: Accurate nodal staging is of utmost importance in patients with lung cancer. FDG-PET/CT imaging is now part of the routine staging. Despite thorough preoperative staging nodal upstaging still occurs in early-stage lung cancer. However, the predictive value of preoperative PET metrics of the primary tumor on nodal upstaging remains to be unexplored. Our aim was to assess the association of these preoperative PET-parameters with nodal upstaging in histologically confirmed lung adenocarcinoma and squamous cell carcinoma. METHODS: From January 2016 to November 2018, 500 patients with pT1-T2/cN0 lung cancer received an anatomical resection with curative intent. 171 patients with adenocarcinoma and squamous cell carcinoma and available PET-CTs were retrospectively included. We analyzed the the association of nodal upstaging with preoperative PET-SUVmax and metabolic PET metrics including total lesion glycolysis (TLG) and metabolic tumor volume (MTV) with different defined thresholds. RESULTS: High values of preoperative PET-SUVmax of the primary tumor were associated with squamous cell carcinoma (p < 0.0001) and with larger tumors (p < 0.0001). Increased preoperative C-reactive protein levels (<1mg/dL) correlated significantly with high preoperative PET-SUVmax values (p < 0.0001). No significant relationship between PET-SUVmax and lactate dehydrogenase activity (p = 0.6818), white blood cell count (p = 0.7681), gender (p = 0.1115) or age (p = 0.9284) was observed. Nodal upstaging rate was 14.0 % with 8.8 % N1 and 5.3 % N2 upstaging. Tumor size (p = 0.0468) and number of removed lymph nodes (p = 0.0461) were significant predictors of nodal upstaging but no significant association was found with histology or PET parameters. Of note, increased MTV - regardless of the threshold - tended to associate with nodal upstaging. CONCLUSION: Early-stage lung cancer patients with squamous histology and T2 tumors presented increased preoperative PET-SUVmax values. Nevertheless, beyond tumor size and number of removed lymph nodes neither SUVmax nor metabolic PET parameters MTV and TLG were significant predictors of nodal upstaging.

Fibroblast-Activation Protein PET and Histopathology in a Single-Center Database of 324 Patients and 21 Tumor Entities.

We present an overview of our prospective fibroblast-activation protein inhibitor (FAPI) registry study across a 3-y period, with head-to-head comparison of tumor uptake in 68Ga-FAPI and 18F-FDG PET, as well as FAP immunohistochemistry. Methods: This is an interim analysis of the ongoing 68Ga-FAPI PET prospective observational trial at our department. Patients who underwent clinical imaging with 68Ga-FAPI PET between October 2018 and October 2021 were included. Tracer uptake was quantified by SUVmax for tumor lesions and by SUVmean for normal organs. PET tumor volume (40% isocontour) and tumor-to-background ratios were calculated. Correlation between SUVmax and FAP staining in tissue samples was analyzed. Results: In total, 324 patients with 21 different tumor entities underwent 68Ga-FAPI imaging; 237 patients additionally received 18F-FDG PET. The most common tumor entities were sarcoma (131/324, 40%), pancreatic cancer (67/324, 21%), and primary tumors of the brain (22/324, 7%). The mean primary tumor SUVmax was significantly higher for 68Ga-FAPI than 18F-FDG among pancreatic cancer (13.2 vs. 6.1, P < 0.001) and sarcoma (14.3 vs. 9.4, P < 0.001), and the same was true for mean SUVmax in metastatic lesions of pancreatic cancer (9.4 vs. 5.5, P < 0.001). Mean primary tumor maximum tumor-to-background ratio was significantly higher for 68Ga-FAPI than 18F-FDG across several tumor entities, most prominently pancreatic cancer (14.7 vs. 3.0, P < 0.001) and sarcoma (17.3 vs. 4.7, P < 0.001). Compared with 18F-FDG, 68Ga-FAPI showed superior detection for locoregional disease in sarcoma (52 vs. 48 total regions detected) and for distant metastatic disease in both sarcoma (137 vs. 131) and pancreatic cancer (65 vs. 57), respectively. Among 61 histopathology samples, there was a positive correlation between 68Ga-FAPI SUVmax and overall FAP immunohistochemistry score (r = 0.352, P = 0.005). Conclusion: 68Ga-FAPI demonstrates higher absolute uptake in pancreatic cancer and sarcoma, as well as higher tumor-to-background uptake along with improved tumor detection for pancreatic cancer, sarcoma, and other tumor entities when compared with 18F-FDG. 68Ga-FAPI is a new tool for tumor staging with theranostic potential.

Histological Validation of FDG and PSMA-Targeted PET/CT Imaging in a Rare Tracheal Adenoid Cystic Carcinoma.

ABSTRACT: Adenoid cystic carcinomas are the second most common entity of tracheal malignancies, which have an overall incidence as low as only 0.2 in 100,000 persons per year. We present the case of a 64-year-old man with a histologically confirmed adenoid cystic carcinoma who sequentially underwent 18F-FDG PET/CT and 68Ga-PSMA-11 PET/CT within 1 day for staging 3 days before surgical resection of the tumor. Immunohistochemistry revealed PSMA expression of the tumor corroborating the PSMA PET findings.

Prediction of malignant lymph nodes in NSCLC by machine-learning classifiers using EBUS-TBNA and PET/CT.

Accurate determination of lymph-node (LN) metastases is a prerequisite for high precision radiotherapy. The primary aim is to characterise the performance of PET/CT-based machine-learning classifiers to predict LN-involvement by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in stage-III NSCLC. Prediction models for LN-positivity based on [18F]FDG-PET/CT features were built using logistic regression and machine-learning models random forest (RF) and multilayer perceptron neural network (MLP) for stage-III NSCLC before radiochemotherapy. A total of 675 LN-stations were sampled in 180 patients. The logistic and RF models identified SUVmax, the short-axis LN-diameter and the echelon of the considered LN among the most important parameters for EBUS-positivity. Adjusting the sensitivity of machine-learning classifiers to that of the expert-rater of 94.5%, MLP (P = 0.0061) and RF models (P = 0.038) showed lower misclassification rates (MCR) than the standard-report, weighting false positives and false negatives equally. Increasing the sensitivity of classifiers from 94.5 to 99.3% resulted in increase of MCR from 13.3/14.5 to 29.8/34.2% for MLP/RF, respectively. PET/CT-based machine-learning classifiers can achieve a high sensitivity (94.5%) to detect EBUS-positive LNs at a low misclassification rate. As the specificity decreases rapidly above that level, a combined test of a PET/CT-based MLP/RF classifier and EBUS-TBNA is recommended for radiation target volume definition.

Effectiveness of durvalumab consolidation in stage III non-small-cell lung cancer: focus on treatment selection and prognostic factors.

The pivotal PACIFIC trial defined durvalumab consolidation as the new standard of care in patients with stage III non-small-cell lung cancer treated with definitive radiochemotherapy. The authors characterized the durvalumab effect after induction chemotherapy according to the ESPATUE trial and definitive radiochemotherapy. All consecutive patients with stage III non-small-cell lung cancer receiving definitive radiochemotherapy between January 2017 and February 2020 were included. Primary end points were progression-free survival and overall survival. Altogether, 160 patients (75 PD-L1-positive, 62 PD-L1-negative, 23 unknown) received definitive radiochemotherapy, 146 (91%) of whom received prior induction chemotherapy. Durvalumab consolidation showed high effectiveness overall and in the good-risk group according to the PACIFIC trial (log-rank test: p < 0.005). Hazard ratios for progression-free survival and overall survival were at the lower limits of those in the PACIFIC trial. These results were robust to adjustment for potential confounders by propensity score weighting. Eastern Cooperative Oncology Group (ECOG) performance status was the most important pretreatment prognostic factor.

The PACIFIC trial is the major landmark trial for stage III non-small-cell lung cancer (NSCLC) patients treated with combined chemoradiation and defined immunotherapy as maintenance treatment and the new standard of care in patients with stage III NSCLC. Here the authors report a retrospective study comparing consecutive stage III NSCLC patients receiving induction chemotherapy and definitive chemoradiation with or without durvalumab consolidation in a high-volume lung cancer center. After induction chemotherapy, chemoradiation and immune checkpoint inhibition, a durable and remarkable tumor response can be achieved in the clinical routine. Consolidation immunotherapy with durvalumab can be confirmed as a strong innovative therapeutic option in NSCLC in almost all subgroups of patients.

Diagnostic Performance of 99mTc-Methoxy-Isobuty-Isonitrile (MIBI) for Risk Stratification of Hypofunctioning Thyroid Nodules: A European Multicenter Study.

99mTc-MIBI (MIBI) imaging is able to exclude malignancy of hypofunctioning thyroid nodules (TNs) with high probability but false positive results are frequent due to low specificity. Therefore, pre-test selection of appropriate TNs is crucial. For image evaluation visual and semiquantitative methods (Washout index, WOInd) are used. Aim of this study was to evaluate the diagnostic performance of MIBI imaging in hypofunctioning TNs with indeterminate fine-needle aspiration cytology results in a multicentric European setting. Patients with hypofunctioning TNs, EU-TIRADS 4 or 5, Bethesda III/IV and MIBI imaging were included. For visual evaluation the intensity of MIBI uptake in the TN was compared to normal thyroid tissue. 358 patients with 365 TNs (n = 68 malignant) were included. Planar imaging (SPECT) showed a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 96% (94%), 21% (22%), 22% (15%), 96% (96%), and 35% (32%). The WOInd (38.9% of all cases, optimal cutoff: -19%) showed a sens 100% (spec 89%, PPV 82%, NPV 100%, ACC 93%). For hypofunctioning TNs at intermediate or high risk with indeterminate cytology, a MIBI negative result on visual evaluation is an effective tool to rule-out thyroid malignancy. The semi-quantitative method could considerably improve overall diagnostic performance of MIBI imaging.

False Positive Ventilation/Perfusion SPECT/CT Mismatch Mimicking Pulmonary Embolism in a Patient With Bilateral Lung Transplant.

ABSTRACT: Ventilation/perfusion SPECT/CT has very high sensitivity with little false-positive findings for diagnosing pulmonary embolism (PE). However, bronchopulmonary tumors or structural changes of the lungs' vasculature infrequently mimic PE. Here, a 59-year-old man presented with acute dyspnea and acute renal failure 5 years after bilateral lung transplant. Pulmonary ventilation/perfusion SPECT/CT was performed demonstrating a lobar mismatch of the left upper lung lobe indicative for PE. Bronchoscopy revealed local hyperemia of this lobe, indicating prolonged venous blood return. Subsequent CT angiography confirmed postsurgical upper pulmonary vein obliteration as final diagnosis. In conclusion, pulmonary vein obliteration might cause false-positive ventilation/perfusion SPECT/CT.