Early response assessment and prediction of overall survival after peptide receptor radionuclide therapy

BACKGROUND: Response after peptide receptor radionuclide therapy (PRRT) can be evaluated using anatomical imaging (CT/MRI), somatostatin receptor imaging ([(68)Ga]Ga-DOTA-TATE PET/CT), and serum Chromogranin-A (CgA). The aim of this retrospective study is to assess the role of these response evaluation methods and their predictive value for overall survival (OS). METHODS: Imaging and CgA levels were acquired prior to start of PRRT, and 3 and 9 months after completion. Tumour size was measured on anatomical imaging and response was categorized according to RECIST 1.1 and Choi criteria. [(68)Ga]Ga-DOTA-TATE uptake was quantified in both target lesions depicted on anatomical imaging and separately identified PET target lesions, which were either followed over time or newly identified on each scan with PERCIST-based criteria. Response evaluation methods were compared with Cox regression analyses and Log Rank tests for association with OS. RESULTS: A total of 44 patients were included, with median follow-up of 31 months (IQR 26–36 months) and median OS of 39 months (IQR 32mo-not reached)d. Progressive disease after 9 months (according to RECIST 1.1) was significantly associated with worse OS compared to stable disease [HR 9.04 (95% CI 2.10–38.85)], however not compared to patients with partial response. According to Choi criteria, progressive disease was also significantly associated with worse OS compared to stable disease [HR 6.10 (95% CI 1.38–27.05)] and compared to patients with partial response [HR 22.66 (95% CI 2.33–219.99)]. In some patients, new lesions were detected earlier with [(68)Ga]Ga-DOTA-TATE PET/CT than with anatomical imaging. After 3 months, new lesions on [(68)Ga]Ga-DOTA-TATE PET/CT which were not visible on anatomical imaging, were detected in 4/41 (10%) patients and in another 3/27 (11%) patients after 9 months. However, no associations between change in uptake on (68)Ga-DOTA-TATE PET/CT or serum CgA measurements and OS was observed. CONCLUSIONS: Progression on anatomical imaging performed 9 months after PRRT is associated with worse OS compared to stable disease or partial response. Although new lesions were detected earlier with [(68)Ga]Ga-DOTA-TATE PET/CT than with anatomical imaging, [(68)Ga]Ga-DOTA-TATE uptake, and serum CgA after PRRT were not predictive for OS in this cohort with limited number of patients and follow-up time.