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Johannes Wienker, Kaid Darwiche, Julia Wälscher, Jane Winantea, Michael Hagemann, Erik Büscher, Abhinav Singla, Christian Taube, Rüdiger Karpf-Wissel Department of Pneumology, University Medicine Essen- Ruhrlandklinik, Essen, Nordrhein-Westfalen, GermanyCorrespondence: Johannes Wienker, Department of Pneumology, University Medicine Essen- Ruhrlandklinik, Tüschener Weg 40, Essen, Nordrhein-Westfalen, 45239, Germany, Tel +49 2014334222, Fax +49 2014331988, Email johannes.wienker@stud.uni-due.deBackground: Bronchoscopic lung volume reduction (BLVR) with endobronchial valves (EBV) can be a successful treatment for end-stage emphysema patients. The reduction of hyperinflation enhances ventilatory mechanics and diaphragm function. Understanding predictors for treatment success is crucial for further improvements.Purpose: The aim of this study was to assess the effect of the target lobe volume reduction (TLVR) in relation to the ipsilateral lung volume reduction (ILVR), affected by the compensatory expansion of the adjacent lobe, on the outcome after BLVR with valves.Patients and Methods: The volumetric relationship of ILVR% to TLVR%, addressed as Reduction Ratio (R), was recorded in 82 patients and compared to changes in lung function, physical performance and quality of life. A small value for R implies a relatively low volume reduction of the ipsilateral lung (ILVR) compared to the volume reduction of the target lobe (TLVR). Additionally, the minimal clinically important difference (MCID) for R was calculated.Results: Patients with a smaller Reduction Ratio (R < 0.2) showed minor improvements at the 3 months follow-up compared to patients with R ≥ 0.2 (mean changes of 39 mL (5.8%), – 395 mL (– 4.9%) and 96 mL (7.1%) versus 231 mL (33%), – 1235 mL (– 20%) and 425 mL (29%) in the forced expiratory volume in 1s (FEV1), residual volume (RV) and inspiratory vital capacity (IVC), respectively, and – 3 m and 0 points versus 20.4 m and – 3.4 points in the 6-minute-walking-distance (6MWD) and COPD assessment test (CAT) score respectively). With a combined value of 0.185, a MCID for R was calculated with established anchors (FEV1, RV, and 6MWD) for emphysema patients.Conclusion: Extensive compensatory hyperinflation of the adjacent non-treated lobe after BLVR results in decreased ILVR, which is responsible for a lack of meaningful improvements in ventilatory mechanics and clinical outcome, despite technically successful lobe volume reduction.Keywords: emphysema, ipsilateral lung volume, reduction ratio, volume shift

Background: Regular disease monitoring with low-dose high-resolution (LD-HR) computed tomography (CT) scans is necessary for the clinical management of people with cystic fibrosis (pwCF). The aim of this study was to compare the image quality and radiation dose of LD-HR protocols between photon-counting CT (PCCT) and energy-integrating detector system CT (EID-CT) in pwCF., Methods: This retrospective study included 23 pwCF undergoing LD-HR chest CT with PCCT who had previously undergone LD-HR chest CT with EID-CT. An intraindividual comparison of radiation dose and image quality was conducted. The study measured the dose-length product, volumetric CT dose index, effective dose and signal-to-noise ratio (SNR). Three blinded radiologists assessed the overall image quality, image sharpness, and image noise using a 5-point Likert scale ranging from 1 (deficient) to 5 (very good) for image quality and image sharpness and from 1 (very high) to 5 (very low) for image noise., Results: PCCT used approximately 42% less radiation dose than EID-CT (median effective dose 0.54 versus 0.93 mSv, p < 0.001). PCCT was consistently rated higher than EID-CT for overall image quality and image sharpness. Additionally, image noise was lower with PCCT compared to EID-CT. The average SNR of the lung parenchyma was lower with PCCT compared to EID-CT (p < 0.001)., Conclusion: In pwCF, LD-HR chest CT protocols using PCCT scans provided significantly better image quality and reduced radiation exposure compared to EID-CT., Relevance Statement: In pwCF, regular follow-up could be performed through photon-counting CT instead of EID-CT, with substantial advantages in terms of both lower radiation exposure and increased image quality., Key Points: Photon-counting CT (PCCT) and energy-integrating detector system CT (EID-CT) were compared in 23 people with cystic fibrosis (pwCF). Image quality was rated higher for PCCT than for EID-CT. PCCT used approximately 42% less radiation dose and offered superior image quality than EID-CT., (© 2024. The Author(s).)

Over 40% stage-III non-small-cell lung cancer (NSCLC) patients (pts) experience 5-year survival following multimodality treatment. Nevertheless, little is known about relevant late toxicities and quality-of-life (QoL) in the further long-term follow-up. Therefore, we invited pts from our randomized phase-III trial (Eberhardt et al., Journal of Clinical Oncology 2015) after 10 years from diagnosis to participate within a structured survivorship program (SSP) including follow-up imaging, laboratory parameters, cardio-pulmonary investigations, long-term toxicity evaluations and QoL questionnaires. Of 246 pts initially accrued, 161 were considered potentially resectable following the induction therapy and were randomized (80 to arm A: definitive chemoradiation; 81 to arm B: definitive surgery; 85 not randomized for different reasons; group C). 31 from 37 pts still alive after 10 years agreed to the SSP (13 in A; 12 in B; 6 in C). Clinically relevant long-term toxicities (grade 3 and 4) were rarely observed with no signal favoring any of the randomization arms. Furthermore, available data from the global QoL analysis did not show a signal favoring any definitive locoregional approach (Mean QoL in SSP A pts: 56.41/100, B pts: 64.39/100) and no late decline in comparison to baseline and early 1-year follow-up. This is the first comprehensive SSP of very late survival follow-up reported in stage-III NSCLC treated within a randomized multimodality trial and it may serve as important baseline information for physicians and pts deciding for a locoregional treatment option., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Rationale: Positron Emission Tomography (PET) using the somatostatin receptor 2 (SSTR2)-antagonist satoreotide trizoxetan ( 68 Ga-SSO120) is a novel, promising imaging modality for small-cell lung cancer (SCLC), which holds potential for theranostic applications. This study aims to correlate uptake in PET imaging with SSTR2 expression in immunohistochemistry (IHC) and to assess the prognostic value of 68 Ga-SSO120 PET at initial staging of patients with SCLC. Methods: We analyzed patients who underwent 68 Ga-SSO120 PET/CT during initial diagnostic workup of SCLC as part of institutional standard-of-care. SSTR2 expression in IHC was evaluated on a 4-level scale and correlated with normalized standardized uptake values and tumor-to-liver ratios (SUV max and TLR peak ) in 68 Ga-SSO120 PET on a lesion level. Highest lesion SUV max /TLR peak per patient, SSTR2 score in IHC, M status according to TNM classification, and other parameters were analyzed for association with overall survival (OS) and time to treatment failure (TTF) by univariate, multivariate (cut-off values were identified on data for best separation), and stratified Cox regression. Results: We included 54 patients (24 men/30 women, median age 65 years, 21 M0/33 M1 according to TNM classification). In 43 patients with available surplus tumor tissue samples, hottest lesion SUV max /TLR peak showed a significant correlation with the level of SSTR2-expression by tumor cells in IHC (Spearman's rho 0.86/0.81, both p < 0.001; ANOVA p < 0.001). High SSTR2 expression in IHC, 68 Ga-SSO120 SUV max and TLR peak of the hottest lesion per patient, whole-body TLR mean , MTV, TLG, M status, and serum LDH showed a significant association with inferior TTF/OS in univariate analysis. In separate multivariate Cox regression (including sex, age, M stage, and LDH) higher hottest-lesion TLR peak showed a significant association with shorter OS (HR = 0.26, 95%CI: 0.08-0.84, p = 0.02) and SSTR2 expression in IHC with significantly shorter TTF (HR = 0.24, 95%CI: 0.08-0.71, p = 0.001) and OS (HR = 0.22, 95%CI: 0.06-0.84, p = 0.03). In total, 12 patients (22.2%) showed low (< 1), 21 (38.9%) intermediate (≥ 1 but < 2), 14 (25.9%) high (≥ 2 but < 5), and 7 (13.0%) very high (≥ 5) whole-body mean TLR mean . Conclusion: In patients with SCLC, SSTR2 expression assessed by 68 Ga-SSO120 PET and by IHC were closely correlated and associated with shorter survival. More than 75% of patients showed higher whole-body 68 Ga-SSO120 tumor uptake than liver uptake and almost 40% high or very high uptake, possibly paving the way towards theranostic applications., Competing Interests: Competing Interests: Filiz Oezkan received personal fees from Sanofi Aventis, Janssen, DeciBio, ERBE and Genentech/Roche Ltd.; program funding to the institution was received from Olympus, Astrazeneca, ERBE and Janssen, all outside the submitted work. Lale Umutlu is a Speaker / Advisory Board Member for Bayer Healthcare and Siemens Healthcare and received research grants from Siemens Healthcare outside the submitted work. Rainer Hamacher was supported by the Clinician Scientist Program of the University Medicine Essen Clinician Scientist Academy (UMEA; Faculty of Medicine and Deutsche Forschungsgemeinschaft [DFG]); reports travel grants from Lilly, Novartis, and PharmaMar; and reports personal fees from Lilly and PharmaMar outside the submitted work. Jens Siveke is supported by German Cancer Aid (grant 70112505, PIPAC; grant 70113834, PREDICT-PACA), the Wilhelm-Sander Foundation (grant 2019.008.1), the DFG through grant SI1549/3-1 (Clinical Research Unit KFO337) and SI1549/4-1, and the Federal Ministry of Education and Research (BMBF; SATURN3 consortium); receives honoraria as a consultant or for continuing medical education presentations from AstraZeneca, Bayer, Immunocore, Roche, and Servier; receives research funding (to the institution) from Bristol Myers Squibb, Celgene, and Roche; and holds ownership and serves on the board of directors of Pharma15—all outside the submitted work. Wolfgang Fendler reports fees from SOFIE Biosciences (research funding), Janssen (consultant, speaker), Calyx (consultant, image review), Bayer (consultant, speaker, research funding), Novartis (speaker, consultant), Telix (speaker), GE Healthcare (speaker), Eczacıbaşı Monrol (speaker), Abx (speaker), Amgen (speaker), and Urotrials, all outside the submitted work. Marcel Wiesweg reports honoraria and advisory role from Amgen, AstraZeneca, Daiichi Sankyo, GlaxoSmithKline, Janssen, Novartis, Pfizer, Roche, Takeda, and research funding from Bristol-Myers Squibb, Takeda outside the submitted work. Ken Herrmann reports personal fees from Bayer, personal fees and other from Sofie Biosciences, personal fees from SIRTEX, non-financial support from ABX, personal fees from Adacap, personal fees from Curium, personal fees from Endocyte, grants and personal fees from BTG, personal fees from IPSEN, personal fees from Siemens Healthineers, personal fees from GE Healthcare, personal fees from Amgen, personal fees from Novartis, personal fees from ymabs, personal fees from Aktis Oncology, personal fees from Theragnostics, personal fees from Pharma15, outside the submitted work. Martin Schuler reports personal fees as a consultant from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Janssen, Merck Serono, Novartis, Roche, Sanofi, and Takeda; honoraria for continuing medical education presentations from Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Janssen, MSD, and Novartis; and research funding (to the institution) from AstraZeneca and Bristol Myers Squibb, all outside the submitted work. Hubertus Hautzel reports personal fees from Roche and Urenco, and other fees from Pari, Roche and Urenco, outside the submitted work. David Kersting reports speaker honoraria from Pfizer and Novartis outside the submitted work. A research grant from Pfizer outside the submitted work and funding by the German Research Foundation (DFG, KE2933/1-1), outside the submitted work., (© The author(s).)

Introduction: Granulomatosis due to immune reconstitution inflammatory syndrome (IRIS) and disseminated Mycobacterium avium-intracellulare (M. avium) infection may trigger hypercalcemia. Here, we report a rare case of hypercalcemia and acute kidney damage related to IRIS in a person living with Human Immunodeficiency Virus (HIV)., Case Presentation: A 39-year-old male person living with HIV presented with muscle weakness and unwanted weight loss of 8 kg within the last 2 weeks. Laboratory findings included serum hypercalcemia of 3.27 mmol/mL associated with elevated calcitriol and acute kidney damage. Since the first diagnosis of HIV and concomitant disseminated M. avium infection, the patient received antiretroviral therapy (ART), rifabutin, clarithromycin, and ethambutol. 18 Fluoro-D-glucose positron emission computed tomography ( 18 FDG-PET/CT) showed progressive multilocular lymphadenopathy. Biopsy specimen from the duodenum as well as retroperitoneal and mediastinal lymph nodes revealed granulomatous inflammation consistent with IRIS. Treatment with forced diuresis, bisphosphonates, and calcitonin normalized serum calcium and kidney function recovered., Conclusion: Hypercalcemia due to IRIS is a rare differential diagnosis in persons living with HIV and may lead to acute kidney damage, despite sufficient ART and antimycobacterial treatment., (© 2024. The Author(s).)

A poor nutritional status is associated with worse pulmonary function and survival in people with cystic fibrosis (pwCF). CF transmembrane conductance regulator modulators can improve pulmonary function and body weight, but more data is needed to evaluate its effects on body composition. In this retrospective study, a pre-trained deep-learning network was used to perform a fully automated body composition analysis on chest CTs from 66 adult pwCF before and after receiving elexacaftor/tezacaftor/ivacaftor (ETI) therapy. Muscle and adipose tissues were quantified and divided by bone volume to obtain body size-adjusted ratios. After receiving ETI therapy, marked increases were observed in all adipose tissue ratios among pwCF, including the total adipose tissue ratio (+ 46.21%, p < 0.001). In contrast, only small, but statistically significant increases of the muscle ratio were measured in the overall study population (+ 1.63%, p = 0.008). Study participants who were initially categorized as underweight experienced more pronounced effects on total adipose tissue ratio (p = 0.002), while gains in muscle ratio were equally distributed across BMI categories (p = 0.832). Our findings suggest that ETI therapy primarily affects adipose tissues, not muscle tissue, in adults with CF. These effects are primarily observed among pwCF who were initially underweight. Our findings may have implications for the future nutritional management of pwCF., (© 2024. The Author(s).)

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 [FEV 1 ], 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 (ΔFEV 1 %, 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 (FEV 1 ) 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., (© 2024. The Author(s).)

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 68 Ga-SSO-120 in comparison to 18 F-FDG PET in the initial staging of SCLC patients. Methods: Patients with newly diagnosed SCLC who underwent additional whole-body 68 Ga-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 18 F-FDG PET/CT was evaluated if available within 2 wk before or after 68 Ga-SSO-120 PET if morphologic differences in CT images were absent. 68 Ga-SSO-120- or 18 F-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. 68 Ga-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 68 Ga-SSO-120 uptake (region-based mean SUV max ≥ 10); 28 patients (90.3%) had average 68 Ga-SSO-120 uptake greater than liver uptake (region-based mean peak tumor-to-liver ratio > 1). In 25 patients with evaluable 18 F-FDG PET, primary tumor, thoracic lymph node metastases, and distant metastases were detected in 100%, 92%, and 64%, respectively, of all investigated patients by 68 Ga-SSO-120 and in 100%, 92%, and 56%, respectively, by 18 F-FDG PET. 68 Ga-SSO-120 PET detected additional contralateral lymph node, liver, and brain metastases in 1, 1, and 2 patients, respectively (no histopathology available), and 18 F-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 68 Ga-SSO-120 and 18 F-FDG uptake was low (Spearman ρ = 0.26-0.33). Conclusion: 68 Ga-SSO-120 PET offers high diagnostic precision with comparable detection rates and additional complementary information to the gold standard, 18 F-FDG PET. Consistent uptake in most patients warrants exploration of SSTR2-directed radionuclide therapy., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Bronchoscopic lung volume reduction (BLVR) via valve implantation can be achieved by targeting severely hyperinflated and emphysematously destructed lung areas in patients with chronic obstructive lung disease. Lack of collateral ventilation (CV) is important for good outcomes with BLVR. CV can be measured using the catheter-based Chartis system. The aim of this study was to evaluate the correlation between total exhaled volume drained from the target lobe measured by Chartis and clinical outcomes after BLVR in CV-negative patients., Methods: From January 2016 to March 2019, 60 patients were included in this retrospective single-center analysis. Drained volume (TVol) measured by Chartis was recorded and compared with lung function and physical performance parameters. Outcome variables included the percentage change in lung function [forced expiratory volume in 1 s (FEV 1 ), residual volume (RV), and inspiratory vital capacity (IVC)]. Secondary outcomes were the degree of target lobe volume reduction (TLVR), change in 6-min walk distance (6MWD), and change in chronic obstructive pulmonary disease (COPD) assessment test (CAT) score., Results: Drained volume correlated significantly with post-BLVR change in FEV 1 ( r  = 0.663), IVC ( r  = 0.611), RV ( r  = -0.368), and TLVR ( r  = 0.635) (all p  < 0.05). In a priori -defined patient subgroups based on drained volume [<100 ml ( n  = 19), 100-400 ml ( n  = 33), and >400 ml ( n  = 8)]; mean changes in FEV 1 were 2.6%, 17.4%, and 51.3%; in RV were -3.9%, -10.6%, and -23.8%; in IVC were -4.0%, 10.6%, and 62.4%; and in TLVR were 525 ml (39%), 1375 ml (73%) and 1760 ml (100%), respectively. There were no significant correlations between absolute and percentage changes in 6MWD and the CAT score. Lung volume reduction was diagnosed in 32 (53%) cases., Conclusion: Drained volume measured by the Chartis system correlated with functional improvement in CV-negative patients undergoing BLVR. The reviews of this paper are available via the supplemental material section.