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PURPOSE: To investigate hypoxia-guided dose-boosting for increased tumour control and improved normal tissue sparing using FMISO-PET images METHODS: Individual tumor-specific control probability (iTSCP) was calculated using a modified linear-quadratic model with rectal-specific radiosensitivity parameters for three limiting-case assumptions of the hypoxia / FMISO uptake relationship. (18) FMISO-PET images from 2 patients (T3N0M0) from the RHYTHM trial (Investigating Hypoxia in Rectal Tumours NCT02157246) were chosen to delineate a hypoxic region (GTV_MISO defined as tumor-to-muscle ratio > 1.3) within the anatomical GTV. Three VMAT treatment plans were created in Eclipse (Varian): STANDARD (45Gy / 25 fractions to PTV4500); BOOST_GTV (simultaneous integrated boost of 60Gy / 25fr to GTV +0.5cm) and BOOST_MISO (60Gy / 25fr to GTV_MISO+0.5cm). GTV mean dose (in EQD2), iTSCP and normal tissue dose-volume metrics (small bowel, bladder, anus, and femoral heads) were recorded. RESULTS: Patient A showed small hypoxic volume (15.8% of GTV) and Patient B moderate hypoxic volume (40.2% of GTV). Dose escalation to 60Gy was achievable, and doses to femoral heads and small bowel in BOOST plans were comparable to STANDARD plans. For patient A, a reduced maximum bladder dose was observed in BOOST_MISO compared to BOOST_GTV (D0.1cc 49.2Gy vs 54.0Gy). For patient B, a smaller high dose volume was observed for the anus region in BOOST_MISO compared to BOOST_GTV (V55Gy 19.9% vs 100%), which could potentially reduce symptoms of fecal incontinence. For BOOST_MISO, the largest iTSCPs (A: 95.5% / B: 90.0%) assumed local correlation between FMISO uptake and hypoxia, and approached iTSCP values seen for BOOST_GTV (A: 96.1% / B: 90.5%). CONCLUSION: Hypoxia-guided dose-boosting is predicted to improve local control in rectal tumors when FMISO is spatially correlated to hypoxia, and to reduce dose to organs-at-risk compared to boosting the whole GTV. This could lead to organ-preserving treatment strategies for locally-advanced rectal cancer, thereby improving quality of life. Oxford Cancer Imaging Centre (OCIC); Cancer Research UK (CRUK); Medical Research Council (MRC).

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Conference paper

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Biomedical modeling, Cancer, Medical image quality, Tissues