Kerrie A Sullivan1, Forough Farrokhyar1, Grigorios I Leontiadis2, Yogita S Patel3, Isabella F Churchill1, Danielle A Hylton1, Feng Xie4, Andrew J E Seely5, Jonathan Spicer6, Biniam Kidane7, Simon R Turner8, Kazuhiro Yasufuku9, Waël C Hanna10. 1. Division of Thoracic Surgery, McMaster University, Hamilton, Ontario, Canada; Department of Health Research Methods, Evidence & Impact, McMaster University, Hamilton, Ontario, Canada. 2. Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada. 3. Division of Thoracic Surgery, McMaster University, Hamilton, Ontario, Canada. 4. Department of Health Research Methods, Evidence & Impact, McMaster University, Hamilton, Ontario, Canada; Centre for Health Economics and Policy Analysis, McMaster University, Hamilton, Ontario, Canada. 5. Division of Thoracic Surgery, University of Ottawa, Ottawa, Ontario, Canada. 6. Division of Thoracic Surgery, McGill University, Montréal, Québec, Canada. 7. Section of Thoracic Surgery, University of Manitoba, Winnipeg, Manitoba, Canada; Research Institute in Oncology and Hematology, Cancer Care Manitoba, Winnipeg, Manitoba, Canada. 8. Division of Thoracic Surgery, University of Alberta, Edmonton, Alberta, Canada. 9. Division of Thoracic Surgery, University of Toronto, Toronto, Ontario, Canada. 10. Division of Thoracic Surgery, McMaster University, Hamilton, Ontario, Canada; Department of Health Research Methods, Evidence & Impact, McMaster University, Hamilton, Ontario, Canada. Electronic address: hannaw@mcmaster.ca.
Abstract
OBJECTIVE: Triple normal lymph nodes, appearing benign on computed tomography, positron emission tomography, and endobronchial ultrasound, have less than a 6% probability of malignancy. We hypothesized that targeted sampling (TS), which omits biopsy of triple normal lymph nodes during endobronchial ultrasound, is not an inferior staging strategy to systematic sampling (SS) of all lymph nodes. METHODS: A prospective randomized feasibility trial was conducted to decide on the progression to a pan-Canadian trial comparing TS with SS. Patients with cN0-N1 non-small cell lung cancer undergoing endobronchial ultrasound were randomized to TS or SS. Lymph nodes in the TS arm crossed over to receive SS. Progression criteria included recruitment rate (70% minimum), procedure length (no significant increase for TS), and incidence of missed nodal metastasis (<6%). Mann-Whitney U test and McNemar's test on paired proportions were used for statistical comparisons. RESULTS: The progression criterion of 70% recruitment rate was achieved early, triggering a planned early stoppage of the trial. Nineteen patients were allocated to each arm. The median procedure length for TS was significantly shorter than SS (3.07 vs 19.07 minutes; P < .001). After crossover analysis, 5.45% (95% confidence interval, 1.87-14.85) of lymph nodes in the TS arm were upstaged from N0 to N2, but this incidence of missed nodal metastasis was below the 6% threshold. During surgical resection, the nodal upstaging incidence from N0 to N2 was 0% for 15 lymph nodes in each arm. CONCLUSIONS: Progression criteria to a pan-Canadian, noninferiority crossover trial comparing TS with SS have been met, and such a trial is warranted.
OBJECTIVE: Triple normal lymph nodes, appearing benign on computed tomography, positron emission tomography, and endobronchial ultrasound, have less than a 6% probability of malignancy. We hypothesized that targeted sampling (TS), which omits biopsy of triple normal lymph nodes during endobronchial ultrasound, is not an inferior staging strategy to systematic sampling (SS) of all lymph nodes. METHODS: A prospective randomized feasibility trial was conducted to decide on the progression to a pan-Canadian trial comparing TS with SS. Patients with cN0-N1 non-small cell lung cancer undergoing endobronchial ultrasound were randomized to TS or SS. Lymph nodes in the TS arm crossed over to receive SS. Progression criteria included recruitment rate (70% minimum), procedure length (no significant increase for TS), and incidence of missed nodal metastasis (<6%). Mann-Whitney U test and McNemar's test on paired proportions were used for statistical comparisons. RESULTS: The progression criterion of 70% recruitment rate was achieved early, triggering a planned early stoppage of the trial. Nineteen patients were allocated to each arm. The median procedure length for TS was significantly shorter than SS (3.07 vs 19.07 minutes; P < .001). After crossover analysis, 5.45% (95% confidence interval, 1.87-14.85) of lymph nodes in the TS arm were upstaged from N0 to N2, but this incidence of missed nodal metastasis was below the 6% threshold. During surgical resection, the nodal upstaging incidence from N0 to N2 was 0% for 15 lymph nodes in each arm. CONCLUSIONS: Progression criteria to a pan-Canadian, noninferiority crossover trial comparing TS with SS have been met, and such a trial is warranted.
Authors: Daniel P Steinfort; Shankar Siva; Kanishka Rangamuwa; Percy Lee; David Fielding; Phan Nguyen; Barton R Jennings; Shaun Yo; Nick Hardcastle; Gargi Kothari; Laurence Crombag; Jouke Annema; Kazuhiro Yasufuku; David E Ost; Louis B Irving Journal: BMC Pulm Med Date: 2022-09-24 Impact factor: 3.320