The potential of proton therapy to reduce acute haematological toxicity in concurrent chemoradiotherapy for oesophageal cancer

: Radiotherapy dose escalation using a simultaneous integrated boost (SIB) is predicted to improve local tumour control in oesophageal cancer, yet any increase in acute haematological toxicity (HT) could limit the predicted improvement in patient outcome. Proton therapy has been shown to significantly reduce HT in lung cancer patients receiving concurrent chemotherapy, we therefore investigated the potential of bone marrow sparing with protons for oesophageal tumours. 21 mid-oesophageal cancer patients treated with conformal radiotherapy (3D50) were selected. Two surrogates for bone marrow were created by outlining thoracic bones (bone) and only the body of the thoracic vertebrae (TV) in Eclipse (Varian). The % overlap of TV with the PTV was recorded for each patient. Additional plans were created retrospectively: a volumetric modulated arctherapy plan (VMAT50) with the same dose as 3D50; a VMAT SIB plan with a dose prescription of 62.5 Gy to the high risk sub-region within the planning treatment volume (VMAT62.5); a re-optimised TV sparing VMAT plan (VMAT62.5bm) and a proton therapy plan (SFO62.5) with the same SIB dose prescription. Bone and TV dose-metrics were recorded and compared across all plans and variation with respect to PTV size and % overlap for each patient was studied. 3D50 plans show the highest bone mean dose and TV V 30Gy values for each patient. VMAT plans irradiate a larger bone V 10Gy volume than 3D50 plans. Re-optimised VMAT62.5bm plans showed improved sparing of the TV volume, but only proton plans showed significant sparing for bone V 10Gy and bone mean dose, especially for patients with larger PTV size. A recent study of 52 lung cancer patients treated with 3D conformal and IMRT found thoracic vertebrae dose parameters (mean dose, V 20Gy and V 30Gy ) to be associated with risk of grade ≥ 3 leukopenia (22) , and a study of 41 oesophageal cancer patients investigated similar dose-volume parameters (thoracic vertebrae mean dose, V 20Gy and V 10Gy ) to propose cut-off values to avoid grade ≥ 3 leukopenia (23). The size and position of target volumes also means that the potential for dose sparing of bone marrow in the thorax may be greater than for the pelvis, especially if IMRT, VMAT or proton therapy are used. While these techniques may improve the conformality of the high dose region, the distribution of low doses (5-15 Gy) is very different with IMRT or VMAT compared to 3D conformal radiotherapy. Proton therapy plans have demonstrated a reduction in bone V 10Gy by 30% and 27% compared to 3D and IMRT plans respectively (24) and reduced HT for lung cancer patients treated with passive scattering protontherapy has been reported (25). Given the proximity and anatomical location of the oesophagus in relationship to the vertebral bodies and the technological capabilities of modern linear accelerators, the potential for bone marrow sparing for individual patients also merits further investigation. This study therefore compares the dose-volume metrics for thoracic bone structures in order to identify differences in dose distribution for a representative group of mid-oesophageal cancer patients from conformal, VMAT and proton therapy treatment techniques. The potential for re-optimising VMAT plans to improve bone marrow sparing or of selecting patients for treatment with proton therapy is also illustrated by comparing dosimetric parameters for individual patients.