Purpose/Objective(s): Clinical evidence suggests that radiation dose received by the hippocampus during whole brain radiotherapy may play a role in radiation-induced neurocognitive decline. To prospectively evaluate the neurocognitive (NC) benefit of hippocampal sparing (PCI-HA), we have developed a phase III clinical trial (PREMER) to test hippocampal sparing during PCI. Materials/Methods: 118 patients undergoing PCI were randomized to receive PCI (nZ60) or PCI-HA (nZ58). The hippocampus was contoured, and hippocampal avoidance regions were created using a 5-mm volumetric expansion around the hippocampus. Linear accelerator ebased intensitymodulated radiotherapy and Volumetric Modulated Arc Therapy treatment plans were generated for a prescription dose of 25 Gy in 10 fractions. The main objective was NC function at 3 months assessed by Free and Cued Selective Reminding Test (FCSRT). The FCSRT is a well-validated and reliable assessment of memory, including encoding, retrieval, and retention of new information over time. Results: These treatment modalities spared the hippocampus, with a D100 of 8.4 AE 2.0 Gy and a maximum dose of 14.5 AE 3.3 Gy. There was a decline in free delayed recall in PCI vs PCI-HA arm at 3 months (21.7 vs 5.1%; p 0.01; OR 5 [IC 95% 1.36-18.87]) at 6 months (32.6 vs 7.3%; p 0.008; OR 6.1 [IC 95% 1.60-23.29]) and at 12 months (18.5 vs 3.8%; p 0.09; OR 5.7 [IC 95% 0.61-52.42])

Our preliminary study demonstrates the feasibility of EGFR determination in bladder washings of patients affected by NMIBC after TUR, during adjuvant treatment and subsequent follow-up. A useful pellet was available in more than 85% of patients, with evidence of up-regulation in 36% of them. Within the high risk category, a significant overexpression of EGFR, mean value of 4.16 folds, was detected. EGFR overexpression might identify a subgroup of high risk tumors inclined to progression despite of intravesical therapy and could represent an additional prognostic factor to select candidates for early radical cystectomy.

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