Rainer J Klement1, Jan-Jakob Sonke2, Michael Allgäuer3, Nicolaus Andratschke4, Steffen Appold5, José Belderbos2, Claus Belka6, Karin Dieckmann7, Hans T Eich8, Michael Flentje9, Inga Grills10, Michael Eble11, Andrew Hope12, Anca L Grosu13, Sabine Semrau14, Reinhart A Sweeney15, Juliane Hörner-Rieber16, Maria Werner-Wasik17, Rita Engenhart-Cabillic18, Hong Ye10, Matthias Guckenberger4. 1. Department of Radiotherapy and Radiation Oncology, Leopoldina Hospital Schweinfurt, Germany. Electronic address: rainer_klement@gmx.de. 2. Department of Radiation Oncology, The Netherland Cancer Institute, Amsterdam, The Netherlands. 3. Department of Radiotherapy, Barmherzige Brüder Regensburg, Germany. 4. Department of Radiation Oncology, University Hospital Zurich, Switzerland. 5. Department of Radiation Oncology, Technische Universität Dresden, Germany. 6. Department of Radiation Oncology, University Hospital of Ludwig-Maximilians-University Munich, Germany. 7. Department of Radiotherapy, Medical University of Vienna, Austria. 8. Department of Radiotherapy, University Hospital Münster, Germany. 9. Department of Radiotherapy and Radiation Oncology, University Hospital Wuerzburg, Germany. 10. Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, USA. 11. Department of Radiation Oncology, RWTH Aachen University, Germany. 12. Department of Radiation Oncology, University of Toronto and Princess Margaret Cancer Center, Canada. 13. Department of Radiation Oncology, University Hospital Freiburg, Germany. 14. Department of Radiation Oncology, Friedrich-Alexander University Erlangen-Nuremberg, Germany. 15. Department of Radiotherapy and Radiation Oncology, Leopoldina Hospital Schweinfurt, Germany. 16. Department of Radiation Oncology, University Hospital Heidelberg, Germany. 17. Department of Radiation Oncology, Thomas Jefferson University Hospital, Philadelphia, USA. 18. Department of Radiotherapy and Radiation Oncology, Phillips-University Marburg, Germany.
Abstract
BACKGROUND: High-dose hypofractionated radiotherapy should theoretically result in a deviation from the typical linear-quadratic shape of the cell survival curve beyond a certain threshold dose, yet no evidence for this hypothesis has so far been found in clinical data of stereotactic body radiotherapy treatment (SBRT) for early-stage non-small cell lung cancer (NSCLC). A pragmatic explanation is a larger α/β ratio than the conventionally assumed 10 Gy. We here attempted an estimation of the α/β ratio for NSCLC treated with SBRT using individual patient data. MATERIALS AND METHODS: We combined two large retrospective datasets, yielding 1294 SBRTs (≤10 fractions) of early stage NSCLC. Cox proportional hazards regression, a logistic tumor control probability model and a biologically motivated Bayesian cure rate model were used to estimate the α/β ratio based on the observed number of local recurrences and accounting for tumor size. RESULTS: A total of 109 local progressions were observed after a median of 17.7 months (range 0.6-76.3 months). Cox regression, logistic regression of 3 year tumor control probability and the cure rate model yielded best-fit estimates of α/β = 12.8 Gy, 14.9 Gy and 12-16 Gy (depending on the prior for α/β), respectively, although with large uncertainties that did not rule out the conventional α/β = 10 Gy. CONCLUSIONS: Clinicians can continue to use the simple LQ formalism to compare different SBRT treatment schedules for NSCLC. While α/β = 10 Gy is not ruled out by our data, larger values in the range 12-16 Gy are more probable, consistent with recent meta-regression analyses.
BACKGROUND: High-dose hypofractionated radiotherapy should theoretically result in a deviation from the typical linear-quadratic shape of the cell survival curve beyond a certain threshold dose, yet no evidence for this hypothesis has so far been found in clinical data of stereotactic body radiotherapy treatment (SBRT) for early-stage non-small cell lung cancer (NSCLC). A pragmatic explanation is a larger α/β ratio than the conventionally assumed 10 Gy. We here attempted an estimation of the α/β ratio for NSCLC treated with SBRT using individual patient data. MATERIALS AND METHODS: We combined two large retrospective datasets, yielding 1294 SBRTs (≤10 fractions) of early stage NSCLC. Cox proportional hazards regression, a logistic tumor control probability model and a biologically motivated Bayesian cure rate model were used to estimate the α/β ratio based on the observed number of local recurrences and accounting for tumor size. RESULTS: A total of 109 local progressions were observed after a median of 17.7 months (range 0.6-76.3 months). Cox regression, logistic regression of 3 year tumor control probability and the cure rate model yielded best-fit estimates of α/β = 12.8 Gy, 14.9 Gy and 12-16 Gy (depending on the prior for α/β), respectively, although with large uncertainties that did not rule out the conventional α/β = 10 Gy. CONCLUSIONS: Clinicians can continue to use the simple LQ formalism to compare different SBRT treatment schedules for NSCLC. While α/β = 10 Gy is not ruled out by our data, larger values in the range 12-16 Gy are more probable, consistent with recent meta-regression analyses.
Authors: Kim Melanie Kraus; Caroline Bauer; Benedikt Feuerecker; Julius Clemens Fischer; Kai Joachim Borm; Denise Bernhardt; Stephanie Elisabeth Combs Journal: Cancers (Basel) Date: 2022-06-15 Impact factor: 6.575
Authors: Annaïg Bertho; Morgane Dos Santos; Sarah Braga-Cohen; Valérie Buard; Vincent Paget; Olivier Guipaud; Georges Tarlet; Fabien Milliat; Agnès François Journal: Front Med (Lausanne) Date: 2021-12-24
Authors: Huei-Tyng Huang; Michael G Nix; Douglas H Brand; David Cobben; Crispin T Hiley; John D Fenwick; Maria A Hawkins Journal: Cancers (Basel) Date: 2022-10-05 Impact factor: 6.575