Session Item

Based on the observation that most local recurrences in breast cancer (BC) undergoing breast-conserving surgery (BCS) occur near the tumor bed, accelerated partial breast irradiation (APBI) has been gaining ground as an attractive alternative in selected patient, with a growing interest in shifting radiotherapy (RT) from postoperative to preoperative setting.The aim of this study is to report preliminary results of the Phase I CRYSTAL trial, in which preoperative RT is delivered in a single fraction using CyberKnife for selected BC patients.

CRYSTAL is a monocentric phase I/II, single-arm and open-label study planning to enroll 79 patients over 5 years.Patients receive an ablative dose to the tumor before surgery using CyberKnife. The primary endpoint for the phase I study is the identification of the maximum tolerated dose (MTD) which meets a specific target toxicity level (no RTOG grade 3-4 toxicity).Dose escalation was designed as a 3+3 rule-based study, proceeding with cohorts of 3 patients testing 3 dose levels: 18Gy,21Gy,24Gy. The minimum of  the phase I population would be 9, if  there was no Grade 3-4 toxicity, to a maximum of 18 if in case of toxicity in each dose escalation step. For the phase II study the aim is the evaluation of treatment efficacy measured in terms of pathological complete response rate. The project was registered at clinicaltrials.gov (NCT04679454) and was approved by institutional Ethical Committee (identification number 1308). Inclusion and exclusion criteria are summarized in Table 1.

From 8/11/2021 to 9/9/2022 a total of 9 patients matching the inclusion criteria were enrolled and treated within the phase I study. Median age was 63.3 years (range 52.5–75.6). At a medium follow up of 6 months (range 1–11) no Grade>2 acute toxicity was observed. All patients underwent 3  breast MRI:before  ablative RT,immediately before surgery,ex-vivo MRI on the excised tumor. Median time to surgery was 33 days (range 28–36). No post-surgical complications were reported. All patients showed a decrease of the KI-67 labeling index between the pre-RT core biopsy and the surgical specimen. No complete pathological response was achieved. Five out of 9 patients had BCS and received post-operative RT to the whole breast. The whole breast RT treatment planning was modified in 2 patients: in one to underdose a lung infiltrate due to asymptomatic radiological pneumonitis, found at the time of CT simulation scan, and in the other one to underdose the part of a rib in order not to exceed the maximum cumulative dose according to the constraints.

Since no Grade>2 toxicity was observed and no dose limiting toxicity  was reached, the phase I study comprised  the minimum number of 9 patients and the 24 Gy dose step will be used for the treatment in the Phase II study. Data on late toxicity,molecular and pathologic assessment of RT-induced changes to study  apoptosis, hypoxia, lymphocitic response and gene expression profile are being collected.