Hypofractionation; who and how Academic Medical Center Radiation Oncology Amsterdam, NL Geertjan van Tienhoven Academisch medisch Centrum Flevoziekenhuis [email protected] Academic Medical Center Radiation Oncology Amsterdam, NL Vught, 11-06-2014 no Take home message Academic Medical Center Radiation Oncology Amsterdam, NL Who? Vught, 11-06-2014 How? Shorter….? Radiation Sensitivity Academic Medical Center Radiation Oncology Amsterdam, NL Vught, 11-06-2014 Dependent upon: Total dose Fraction dose Overall treatment time α/β value tissues Biological basis Academic Medical Center Radiation Oncology Vught, 11-06-2014 Amsterdam, NL Linear quadratic model: S (D) = e-αD -βD α/β value is specific per tissue type Therapeutic width Academic Medical Center Radiation Oncology Amsterdam, NL Vught, 11-06-2014 %control 100 Tumour Normal tissues 50 65 Dose (Gy) Biological basis Academic Medical Center Radiation Oncology Tumour more sensitive Fraction Surviving cells Vught, 11-06-2014 Amsterdam, NL Repair and repopulation normal tissue more efficient Normal tissue Tumour Dose (Gy) Fractionation better if α/β value of tumours >> α/β normal tissues 1990’s Academic Medical Center Radiation Oncology Amsterdam, NL All curative scheme’s Fractiondose 2 Gy (Europe) 7 wks (incl boost) Fractiondose 1.8 Gy (VS) 5-6 wks Manchester Vught, 11-06-2014 Fractiondose 2.67 (3 weken) Radiotherapy Action Group Exposure Three large RCT’s Academic Medical Center Radiation Oncology Amsterdam, NL START A Trial 50 Gy 39 Gy 42.9 Gy 25 fx 13 fx 13 fx 2.0 Gy 3.0 Gy 3.3 Gy 5 weken 5 weken 5 weken 749 737 750 2.0 Gy 5 weken 2.67 Gy 3 weken 1105 1110 START B Trial 50 Gy 40 Gy 25 fx 15 fx Vught, 11-06-2014 Toronto Trial 50 Gy 42.5 Gy 25 fx 16 fx 2.0 Gy 5 weken 2.66 Gy 3 wk 1 dag 612 622 Toronto hypofractionation trial Academic Medical Center Radiation Oncology Amsterdam, NL Vught, 11-06-2014 Whelan, NEJM 2010 1234 patients Toronto hypofractionation trial Academic Medical Center Radiation Oncology Vught, 11-06-2014 Whelan, NEJM 2010 Amsterdam, NL Excellent to good cosmesis: 71.3 vs 69.8% (NS) Start A and B trials Academic Medical Center Radiation Oncology Haviland, Lancet Oncol 2013 Vught, 11-06-2014 Amsterdam, NL Start A and B trials Academic Medical Center Radiation Oncology Amsterdam, NL 9.9 years Toxicity seems even less with hypofractionation Haviland, Lancet Oncol 2013 Vught, 11-06-2014 9.3 years Proof of principle Academic Medical Center Radiation Oncology Amsterdam, NL Hypofractionation works in breast cancer Vught, 11-06-2014 Apparently α/β breast cancer is low As is α/β of normal tissues Dutch situation Academic Medical Center Radiation Oncology Amsterdam, NL LPRM working party Whole breast/chest wall Advice: hypofractionation 16 fx 2.66 Gy Boost Vught, 11-06-2014 Normal: 5 fx 2.66 Gy High: 7 fx 2.66 Gy Or simultaneous integrated Regional No advice LPRM……..but…… Future…….. FAST?? Academic Medical Center Radiation Oncology FAST Trial Vught, 11-06-2014 50 Gy 25 fx 28.5 Gy 5 fx 30 Gy 5 fx 5wk 5wk 5wk 915 patients randomized End point: cosmesis 37 months follow up FAST Trialists Group, R&O 2011 Amsterdam, NL FAST trial Academic Medical Center Radiation Oncology FAST Trialists Group, R&O 2011 Vught, 11-06-2014 Amsterdam, NL Dank voor de aandacht Academic Medical Center Radiation Oncology Vught, 11-06-2014 Amsterdam, NL [email protected]
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