Treatment Assessment of pNET and NELM after Everolimus by Quantitative MRI Parameters

Abstract

Assessment of treatment response to targeted therapies such as everolimus is difficult, especially in slow-growing tumors such as NETs. In this retrospective study, 17 patients with pancreatic neuroendocrine tumors (pNETs) and hepatic metastases (NELMs) (42 target lesions) who received everolimus were analyzed. Intralesional signal intensities (SI) of non-contrast T1w, T2w and DCE imaging, and apparent diffusion coefficients (ADCmean and ADCmin) of DWI, were measured on baseline and first follow-up MRI after everolimus initiation. Response assessment was categorized according to progression-free survival (PFS), with responders (R) showing a PFS of ≥11 months. ADCmin of NELMs decreased in Rs whereas it increased in non-responders (NR). Percentual changes of ADCmin and ADCmean differed significantly between response groups (p < 0.03). By contrast, ADC of the pNETs tended to increase in Rs, while there was no change in NRs. Tumor-to-liver (T/L) ratio of T1 SI of NELMs increased in Rs and decreased in NRs, and percentual changes differed significantly between response groups (p < 0.02). T1 SI of the pNETs tended to decrease in Rs and increase in Ns. The quotient of pretherapeutic and posttherapeutic ADCmin values (DADCmin) and length of everolimus treatment showed significant association with PFS in univariable Cox analysis. In conclusion, quantitative MRI, especially DWI, seems to allow treatment assessment of pNETs with NELMs under everolimus. Interestingly, the responding NELMs showed decreasing ADC values, and there might be an opposite effect on ADC and T1 SI between NELMs and pNETs.

Quantitative SSTR-PET/CT for predicting response and survival outcomes in patients with pancreatic neuroendocrine tumors receiving CAPTEM

“…These observations might be related to the small number of total pNET (n = 16). Another possibility is that functional / morphological changes might be different between liver metastasis and the primary tumor as discussed by Ingenerf et al 28 The Choi et al response criteria suggested that changes in tumor attenuation could better represent treatment response to imatinib in gastrointestinal stromal tumors. 29 While Choi et al found a decrease in tumor density of more than 15% on CT had a sensitivity of 97% and a specificity of 100% in identifying PET responders versus 52% and 100% by RECIST, we observed a slight, but statistically significant decrease in HU values in nonresponding lesions (p = 0.02), while no significant change was observed in responding lesions.…”

Utility of clinical and MR imaging parameters for prediction and monitoring of response to capecitabine and temozolomide (CAPTEM) therapy in patients with liver metastases of neuroendocrine tumors

“…Parameters such as signal intensity (SI) on T1-weighted or T2-weighted images, tumor vascularization, and apparent diffusion coefficient (ADC) derived from DWI are increasingly scrutinized for their predictive and monitoring potential across various therapy regimens. 8 , 9 , 10 , 11 Notably, no prior study has assessed the utility of these MRI parameters for monitoring therapy or predicting CAPTEM response in patients with hepatic metastasized NETs. Therefore, this study aims to evaluate clinical, morphological, and functional imaging factors for their ability to predict and monitor therapy response in metastatic NET patients undergoing CAPTEM treatment.…”

Synchronous neuroendocine liver metastases in comparison to primary pancreatic neuroendocrine tumors on MRI and SSR-PET/CT

“…demonstrated that there are differences between pNET and its metastases: ADCmin values of NELM decreased significantly in responders following the initiation of everolimus treatment, whereas ADC values in nonresponders increased. Conversely, ADC (both minimum and mean) of pNETs tended to increase in responders, while there was no change observed in nonresponders, indicating distinct behavior between pNETs and their NELM counterparts ( 19 ).…”