周一“星”视角|SBRT可治疗无法手术的早期中央型NSCLC；电子鼻技术在I期肺癌中的价值：一项真实世界评估

01

Antonin Levy1, Sonja Adebahr2,3, Coen Hurkmans4, Merina Ahmed5, Shahreen Ahmad6, Matthias Guckenberger7, Xavier Geets8, Yolande Lievens9, Maarten Lambrecht10,11, Nicolas Pourel12, Victor Lewitzki13, Krzysztof Konopa14, Kevin Franks15, Rafal Dziadziuszko14, Fiona McDonald5, Catherine Fortpied16, Enrico Clementel16, Béatrice Fournier16, Stefania Rizzo17, Christian Fink18,19, Oliver Riesterer7,20, Heike Peulen21,22, Nicolaus Andratschke7, Alan McWilliam23, Eleni Gkika2,3,24, Tanja Schimek-Jasch2,3, Anca-Ligia Grosu2,3, Cécile Le Pechoux1, Corinne Faivre-Finn23, Ursula Nestle2,25

1 Gustave Roussy, Université Paris Saclay, Department of Radiation Oncology, Villejuif, France

2 University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Department of Radiation Oncology, Freiburg, Germany

3 German Cancer Consortium (DKTK), Partner Site Freiburg, Freiburg, Germany;

4 Catharina Hospital, Department of Radiation Oncology, Eindhoven, The Netherlands

5 Royal Marsden NHS Foundation Trust/Institute of Cancer Research, Department of Radiotherapy, Sutton, United Kingdom

6 Guy's & St Thomas' NHS Foundation Trust, Department of Oncology and Radiotherapy, London, United Kingdom

7 University Hospital Zurich, University of Zurich, Department of Radiation Oncology, Zurich, Switzerland

8 Cliniques universitaires Saint-Luc, MIRO - IREC Lab, Department of Radiation Oncology, Brussels, Belgium

9 Ghent University Hospital and Ghent University, Department of Radiation Oncology, Ghent, Belgium

10 UZ Gasthuisberg Leuven , Department of Radiotherapy-Oncology, Leuven, Belgium

11 KU Leuven, Laboratory of experimental Radiotherapy , Leuven, Belgium

12 Institut Sainte-Catherine, Service de radiothérapie, Avignon, France

13 University Hospital Würzburg, Department of Radiation Oncology, Würzburg, Germany

14 Medical University of Gdansk, Department of Oncology and Radiotherapy, Gdansk, Poland

15 St. James's University Hospital, Department of Clinical Oncology, Leeds, United Kingdom

16 EORTC, Headquarters, Brussels, Belgium

17 Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Università della Svizzera Italiana, Lugano, Switzerland

18 Allgemeines Krankenhaus, AKH Celle, Celle, Germany

19 Department of Radiology and Nuclear Medicine, University Medical Centre Mannheim, Heidelberg University, Mannheim, Germany

20 Kantonsspital Aarau, Radio-Onkologie-Zentrum KSA-KSB, Aarau, Switzerland

21 Catharina Hospital, Department of Radiation Oncology, Eindhoven, The Netherlands

22 Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

23 University of Manchester, The Christie NHS Foundation Trust, Division of Cancer Sciences, Manchester, United Kingdom

24 Department of Radiation Oncology, University Hospital Bonn, University of Bonn, Bonn, Germany

25 Kliniken Maria Hilf GmbH Mönchengladbach, Department of Radiation Oncology, Mönchengladbach, Germany

Background: 

The international EORTC phase II single-arm LungTech trial 22113-08113 assessed safety and efficacy of stereotactic body radiotherapy (SBRT) in patients with centrally located early-stage non-small cell lung cancer (NSCLC).

Methods: 

Patients with inoperable non-metastatic central NSCLC (T1-T3 N0 M0, ≤7cm) were included. After prospective central imaging review and radiation therapy quality assurance (RTQA) for any eligible patient, SBRT (8x7.5 Gy, ICRU 83) was delivered. The primary endpoint was freedom from local progression probability at three years after start of SBRT.

Results: 

The trial was closed earlier due to poor accrual related to repeated safety-related pauses in recruitment. Between 08/2015 and 12/2017, 39 patients from 6 European countries were included and 31 were treated per protocol and analyzed. Patients were mainly male (58%) with a median age of 75 years. Baseline comorbidities were mainly respiratory (68%) and cardiac (48%). Median tumor size was 2.6 cm (range, 1.2-5.5) and most cancers were T1 (51.6%) or T2a (38.7%) N0 M0 and of squamous cell origin (48.4%). Median follow-up was 3.6 years. The 3-year freedom from local progression and overall survival rates were 81.5% (90% CI: 62.7-91.4%) and 61.1% (90%CI: 44.1-74.4%), respectively. Cumulative incidence rates of local, regional and distant progression at 3 years were 6.7% (90% CI: 1.6-17.1%), 3.3% (90% CI: 0.4-12.4%) and 29.8% (90% CI: 16.8-44.1%), respectively. SBRT-related acute and late AEs ≥ G3 were reported in 6.5% (n=2, including one G5 pneumonitis in a patient with prior interstitial lung disease) and 19.4 % (n=6, including one lethal hemoptysis after a lung biopsy in a patient receiving anticoagulants), respectively.

Conclusion:

The LungTech trial suggests that SBRT with 8×7.5Gy for central lung tumors in inoperable patients is associated with acceptable local control rates. However, late severe adverse events may occur after completion of treatment. This SBRT regimen is a viable treatment option after thorough risk-benefit discussion with patients. To minimize potentially fatal toxicity, careful management of dose constraints and post-SBRT interventions is crucial.

[CITATION]:Levy A, Adebahr S, Hurkmans C, et al.  Stereotactic body radiotherapy for centrally located inoperable early-stage NSCLC: EORTC 22113-08113 LungTech phase II trial results. J Thorac Oncol. 2024 May 22:S1556-0864(24)00577-X.

[DOI]: https:// doi.org/10.1016/j.jtho.2024.05.366.

[IF]:20.4

02

Gaetano Rocco¹, Giorgio Pennazza², Kay See Tan³, Stijn Vanstraelen⁴, Marco Santonico⁵, Robert J Corba⁴, Bernard J Park⁴, Smita Sihag⁴, Matthew J Bott⁴, Pierfilippo Crucitti⁶, James M Isbell⁴, Michelle S Ginsberg⁷, Hallie Weiss⁸, Raffaele Antonelli Incalzi⁹, Panaiotis Finamore⁶, Filippo Longo⁶, Alessandro Zompanti², Simone Grasso⁵, Stephen B Solomon⁷, Alain Vincent⁴, Alexa McKnight⁴, Michael Cirelli⁴, Carmela Voli⁴, Susan Kelly⁴, Mario Merone¹⁰, Daniela Molena⁴, Katherine Gray⁴, James Huang⁴, Valerie W Rusch⁴, Manjit S Bains⁴, Robert J Downey⁴, Prasad S Adusumilli⁴, David R Jones¹¹

1 Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address: roccog@mskcc.org.

2 Department of Engineering, Unit of Electronics for Sensor Systems, Università Campus Bio-Medico di Roma, Rome, Italy.

3 Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.

4 Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.

5 Department of Science and Technology for Sustainable Development and One Health, Unit of Electronics for Sensor Systems, Università Campus Bio-Medico di Roma, Rome, Italy.

6 Department of Thoracic Surgery, Università Campus Bio-Medico di Roma, Rome, Italy.

7 Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.

8 Department of Anesthesiology, Memorial Sloan Kettering Cancer Center, New York, New York.

9 Department of Geriatrics, Research Unit of Internal Medicine, Università Campus Bio-Medico di Roma, Rome, Italy.

10 Department of Engineering, Unit of Computational Systems and Bioinformatics, Università Campus Bio-Medico di Roma, Rome, Italy.

11 Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York; Druckenmiller Center for Lung Cancer Research, Memorial Sloan Kettering Cancer Center, New York, New York.

Objective: 

Electronic nose (E-nose) technology has demonstrated excellent sensitivity and specificity in the setting of lung cancer screening. However, the performance of E-nose specifically for early-stage tumors remains unclear. Therefore, the aim of our study was to assess the diagnostic performance of E-nose technology in clinical stage I lung cancer.

Methods: 

This Phase-IIc trial (NCT04734145) included patients diagnosed with a single ≥50% solid stage I nodule. Exhalates were prospectively collected from January 2020 to August 2023. Blinded bioengineers analyzed the exhalates, using E-nose technology to determine the probability of malignancy. Patients were stratified into 3 risk groups (low-risk, <0.2; moderate risk, ≥0.2 to 0.7; high-risk, ≥0.7). The primary outcome was the diagnostic performance of E nose versus histopathology (accuracy and F1 score). The secondary outcome was the clinical performance of the E-nose versus clinicoradiological prediction models.

Results: 

Based on the predefined cut-off (<0.20), E-nose agreed with histopathological results in 86% of cases, achieving an F1 score of 92.5%, based on 86 true positives, 2 false negatives, and 12 false positives (n=100). Compared with Swensen and Brock models, E-nose would refer fewer patients with malignant nodules to observation (Low-risk: 2 vs. 9 and 11; respectively; P=0.028 and P=0.011) and more patients with malignant nodules to treatment without biopsy (High-risk: 27 vs. 19 and 6; respectively; P=0.057 and P<0.001).

Conclusions: 

In the setting of clinical stage I lung cancer, E-nose has good agreement with histopathology. Accordingly, E-nose technology can be used in addition to imaging or as part of a “multiomics” platform.

[CITATION]: Rocco G, Pennazza G, Tan KS, et al. A real-world assessment of stage I lung cancer through electronic nose technology.J Thorac Oncol. 2024 May 16:S1556-0864(24)00211-9.

[DOI]: 10.1016/j.jtho.2024.05.006.

[IF]: 20.4