Pamela Samson1, Kathleen Keogan2, Traves Crabtree1, Graham Colditz3, Stephen Broderick4, Varun Puri1, Bryan Meyers5. 1. Washington University in St. Louis, Division of Cardiothoracic Surgery, United States. 2. Washington University in St. Louis, Division of Biostatistics, United States. 3. Washington University in St. Louis, Department of Surgery, Division of Public Health Science, United States. 4. St. Luke's Hospital, Division of Cardiothoracic Surgery, United States. 5. Washington University in St. Louis, Division of Cardiothoracic Surgery, United States. Electronic address: meyersb@wudosis.wustl.edu.
Abstract
OBJECTIVES: To identify the variability of short- and long-term survival outcomes among closed Phase III randomized controlled trials with small sample sizes comparing SBRT (stereotactic body radiation therapy) and surgical resection in operable clinical Stage I non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Clinical Stage I NSCLC patients who underwent surgery at our institution meeting the inclusion/exclusion criteria for STARS (Randomized Study to Compare CyberKnife to Surgical Resection in Stage I Non-small Cell Lung Cancer), ROSEL (Trial of Either Surgery or Stereotactic Radiotherapy for Early Stage (IA) Lung Cancer), or both were identified. Bootstrapping analysis provided 10,000 iterations to depict 30-day mortality and three-year overall survival (OS) in cohorts of 16 patients (to simulate the STARS surgical arm), 27 patients (to simulate the pooled surgical arms of STARS and ROSEL), and 515 (to simulate the goal accrual for the surgical arm of STARS). RESULTS:From 2000 to 2012, 749/873 (86%) of clinical Stage I NSCLC patients who underwent resection were eligible for STARS only, ROSEL only, or both studies. When patients eligible for STARS only were repeatedly sampled with a cohort size of 16, the 3-year OS rates ranged from 27 to 100%, and 30-day mortality varied from 0 to 25%. When patients eligible for ROSEL or for both STARS and ROSEL underwent bootstrapping with n=27, the 3-year OS ranged from 46 to 100%, while 30-day mortality varied from 0 to 15%. Finally, when patients eligible for STARS were repeatedly sampled in groups of 515, 3-year OS narrowed to 70-85%, with 30-day mortality varying from 0 to 4%. CONCLUSION: Short- and long-term survival outcomes from trials with small sample sizes are extremely variable and unreliable for extrapolation.
RCT Entities:
OBJECTIVES: To identify the variability of short- and long-term survival outcomes among closed Phase III randomized controlled trials with small sample sizes comparing SBRT (stereotactic body radiation therapy) and surgical resection in operable clinical Stage I non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Clinical Stage I NSCLCpatients who underwent surgery at our institution meeting the inclusion/exclusion criteria for STARS (Randomized Study to Compare CyberKnife to Surgical Resection in Stage I Non-small Cell Lung Cancer), ROSEL (Trial of Either Surgery or Stereotactic Radiotherapy for Early Stage (IA) Lung Cancer), or both were identified. Bootstrapping analysis provided 10,000 iterations to depict 30-day mortality and three-year overall survival (OS) in cohorts of 16 patients (to simulate the STARS surgical arm), 27 patients (to simulate the pooled surgical arms of STARS and ROSEL), and 515 (to simulate the goal accrual for the surgical arm of STARS). RESULTS: From 2000 to 2012, 749/873 (86%) of clinical Stage I NSCLCpatients who underwent resection were eligible for STARS only, ROSEL only, or both studies. When patients eligible for STARS only were repeatedly sampled with a cohort size of 16, the 3-year OS rates ranged from 27 to 100%, and 30-day mortality varied from 0 to 25%. When patients eligible for ROSEL or for both STARS and ROSEL underwent bootstrapping with n=27, the 3-year OS ranged from 46 to 100%, while 30-day mortality varied from 0 to 15%. Finally, when patients eligible for STARS were repeatedly sampled in groups of 515, 3-year OS narrowed to 70-85%, with 30-day mortality varying from 0 to 4%. CONCLUSION: Short- and long-term survival outcomes from trials with small sample sizes are extremely variable and unreliable for extrapolation.
Authors: Achilles J Fakiris; Ronald C McGarry; Constantin T Yiannoutsos; Lech Papiez; Mark Williams; Mark A Henderson; Robert Timmerman Journal: Int J Radiat Oncol Biol Phys Date: 2009-02-27 Impact factor: 7.038
Authors: Mojgan Taremi; Andrew Hope; Max Dahele; Shannon Pearson; Sharon Fung; Thomas Purdie; Anthony Brade; John Cho; Alexander Sun; Jean-Pierre Bissonnette; Andrea Bezjak Journal: Int J Radiat Oncol Biol Phys Date: 2011-03-04 Impact factor: 7.038
Authors: Traves D Crabtree; Chadrick E Denlinger; Bryan F Meyers; Issam El Naqa; Jennifer Zoole; A Sasha Krupnick; Daniel Kreisel; G Alexander Patterson; Jeffrey D Bradley Journal: J Thorac Cardiovasc Surg Date: 2010-04-18 Impact factor: 5.209
Authors: Joe Y Chang; Suresh Senan; Marinus A Paul; Reza J Mehran; Alexander V Louie; Peter Balter; Harry J M Groen; Stephen E McRae; Joachim Widder; Lei Feng; Ben E E M van den Borne; Mark F Munsell; Coen Hurkmans; Donald A Berry; Erik van Werkhoven; John J Kresl; Anne-Marie Dingemans; Omar Dawood; Cornelis J A Haasbeek; Larry S Carpenter; Katrien De Jaeger; Ritsuko Komaki; Ben J Slotman; Egbert F Smit; Jack A Roth Journal: Lancet Oncol Date: 2015-05-13 Impact factor: 41.316
Authors: Bryan A Whitson; Rafael S Andrade; Adam Boettcher; Ricardo Bardales; Robert A Kratzke; Peter S Dahlberg; Michael A Maddaus Journal: Ann Thorac Surg Date: 2007-06 Impact factor: 4.330
Authors: DuyKhanh P Ceppa; Andrzej S Kosinski; Mark F Berry; Betty C Tong; David H Harpole; John D Mitchell; Thomas A D'Amico; Mark W Onaitis Journal: Ann Surg Date: 2012-09 Impact factor: 12.969
Authors: Julie K Jang; Scott M Atay; Li Ding; Elizabeth A David; Sean C Wightman; Anthony W Kim; Jason C Ye Journal: Am J Clin Oncol Date: 2022-04-01 Impact factor: 2.339