Escalation and Intensification of Radiotherapy for Stage III Non-small Cell Lung Cancer: Opportunities for Treatment Improvement |
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| Authors: | J.D. Fenwick A.E. Nahum Z.I. Malik C.V. Eswar M.Q. Hatton V.M. Laurence J.F. Lester D.B. Landau |
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| Affiliation: | 2. School of Cancer Studies, Liverpool University, Royal Liverpool University Hospital, Daulby Street, Liverpool L69 3GA, UK;3. Department of Clinical Oncology, Clatterbridge Centre for Oncology, Clatterbridge Road, Wirral CH63 4JY, UK;4. Department of Clinical Oncology, Weston Park Hospital, Witham Road, Sheffield S10 2SJ, UK;5. Department of Clinical Oncology, Velindre Hospital, Whitchurch, Cardiff CF14 2TL, UK;1. 21st Century Oncology/Michigan Healthcare Professionals, Farmington Hills, USA;2. Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, USA;3. Department of Radiation Oncology, University of Wuerzburg, Germany;4. Department of Radiation Oncology, Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands;5. Princess Margaret Hospital, University of Toronto, Canada;6. Department of Radiation Oncology, Thomas Jefferson University Hospital, Philadelphia, USA;1. Department of Radiation Oncology, Clatterbridge Cancer Centre NHS Foundation Trust, Bebington, United Kingdom;2. National Clinical Analysis and Specialised Applications Team (NATCANSAT), Clatterbridge Cancer Centre NHS Foundation Trust, Bebington, United Kingdom;3. Department of Molecular and Clinical Cancer Medicine, Institute of Translational Medicine, University of Liverpool, United Kingdom;1. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas;2. Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas;3. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas;4. Department of Biostatatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas;6. Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas;1. Agostino Gemelli Hospital, Rome, Italy;2. Niguarda Ca’ Granda Hospital, Milan, Italy;3. University of Modena, Modena, Italy;4. IRCCS Foundation Ca’ Granda Maggiore Hospital, Milan, Italy;5. University of Bari, Bari, Italy;6. University of Udine, Udine, Italy;7. Ospedali Riuniti, Bergamo, Italy;8. Sant’Orsola Malpighi Hospital, Bologna, Italy;9. University of Padua, Padua, Italy;10. San Camillo Spallanzani Hospital, Rome, Italy;11. Sapienza University, Rome, Italy;12. University of Torvergata, Rome, Italy;1. Washington University, St Louis, MO, USA;2. Radiation Therapy Oncology Group-Statistical Center, Philadelphia, PA, USA;3. The University of Texas MD Anderson Cancer Center, Houston, TX, USA;4. Christiana Care/Helen Graham Medical Center, Newark, DE, USA;5. Mayo Clinic, Scottsdale, AZ, USA;6. Mayo Clinic, Rochester, MN, USA;7. SUNY Upstate Medical University, Syracuse NY, USA;8. H Lee Moffitt Cancer Center, Tampa, FL, USA;9. USON- Texas Oncology-Sugarland, Sugarland, TX, USA;10. Michigan Cancer Research Consortium CCOP, Ypsilanti, MI, USA;11. University of Texas Southwestern, Dallas, TX, USA;12. UPMC-Shadyside Hospital, Pittsburgh, PA, USA;13. Christiana Care Health CCOP, Newark, DE, USA;14. The Ottawa Hospital Cancer Centre, Ottawa, Canada;15. Emory University, Atlanta, GA, USA;p. Kansas City CCOP, Kansas City, MO, USA |
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| Abstract: | In this overview we review and model how radiotherapy tumour control and complication rates vary with dose, fractionation, schedule duration, irradiated volume and use of chemotherapy for stage III non-small cell lung cancer (NSCLC), and use the modelling to study the effectiveness of different NSCLC dose-escalation approaches being developed in the UK. Data have been collated for pneumonitis, lung fibrosis, early and late oesophagitis, cord and cardiac complications, and local progression-free survival at 30 months. Dependences of the various end points on treatment-related factors are catalogued and analysed using the linear-quadratic incomplete repair model to account for dose and fractionation effects, making linear corrections for differences in schedule duration, and loosely characterising volume effects using parallel- and series-type concepts. Tolerance limits are calculated for the different end points and distilled into ranges of prescribed dose likely to be tolerable when delivered in 2.5 and 4 week radiation and 6 week chemoirradiation schedules using conformal techniques. Worthwhile (～20%) gains in 30 month local progression-free survival should be achievable at safely deliverable levels of dose escalation. The analysis suggests that longer schedules may be more beneficial than shorter ones, but this finding is governed by the relative rates of tumour and oesophageal accelerated proliferation, which are quite imprecisely known. Consequently escalated 2.5, 4 and 6 week schedules are being developed; each should lead to useful improvements in local control but it is not yet known which schedule will be most effective. |
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