Background: The ocular involvement of neuroendocrine neoplasms (NENs) is uncommon and mainly represented by metastases from gastrointestinal and lung neuroendocrine tumors. Primary orbital NENs are even less common and their diagnostic and therapeutic management is a challenge. Methods: A systematic review of the literature was conducted from 1966 to September 2023 on PubMed to identify articles on orbital NENs and to summarize their clinical–pathological features, diagnosis and therapeutic management. Furthermore, we presented a case of a locally advanced retro-orbital primary neuroendocrine tumor that was referred to the certified Center of Excellence of Sant’Andrea Hospital, La Sapienza University of Rome, Italy. Results: The final analysis included 63 records on orbital NENs and 11 records focused on primary orbital NENs. The localization was mostly unilateral and in the right orbit; proptosis or exophthalmos represented the initial symptoms. The diagnostic work-up and therapeutic management was discussed and a diagnostic algorithm for the suspicion of primary orbital NENs was proposed. Conclusions: A multidisciplinary approach is required for the management of primary orbital NENs, emphasizing the importance of early referral to dedicated centers for prompt differential diagnosis, tailored treatment, and an improved quality of life and survival.

Background: This exploratory study assessed whether qualitative dynamic contrast-enhanced MRI (DCE-MRI) time–intensity curves (TICs) differentiate non-progressive treatment-related changes (NPTRC) from tumor progression after stereotactic radiotherapy for brain metastases. Methods: Thirty-two patients with 51 treated lesions underwent DCE-MRI. Five neuroradiologists independently delineated a volume of interest and classified the resulting TIC as Type A–D. Longitudinal clinical and MRI follow-up provided the reference outcome, which was recorded before the TIC framework was finalized. An A/B versus C/D grouping was evaluated as a secondary exploratory analysis. Results: Thirty-five lesions were classified as NPTRC and 16 as tumor progression. All 17 Type A lesions were NPTRC, whereas all 13 Type C/D lesions showed progression. Type B was observed in 21 of 51 lesions (41.2%), including 18 NPTRC and 3 progressive lesions, representing a substantial indeterminate subgroup. The exploratory A/B versus C/D grouping yielded 81.3% sensitivity and 100% specificity. The ordinal TIC analysis yielded an AUC of 0.952. Interobserver agreement was high within the present reader group (Fleiss’ κ = 0.889). Conclusions: Type A was associated with NPTRC, Types C/D were associated with progression, and Type B represented an indeterminate pattern. These descriptive findings require independent validation before clinical use.

Background: This exploratory study assessed whether qualitative dynamic contrast-enhanced MRI (DCE-MRI) time–intensity curves (TICs) differentiate non-progressive treatment-related changes (NPTRC) from tumor recurrence after stereotactic radiotherapy for brain metastases. Methods: Thirty-two patients with 51 treated lesions underwent DCE-MRI. Five neuroradiologists inde-pendently delineated a volume of interest and classified the resulting TIC as Type A–D. Longitudinal clinical and MRI follow-up provided the reference outcome, which was recorded before the TIC framework was finalized. An A/B versus C/D grouping was evaluated as a secondary exploratory analysis. Results: Thirty-five lesions were classified as NPTRC and 16 as tumor recurrence. All 17 Type A lesions were NPTRC, and all 13 Type C/D lesions showed recurrence. Type B occurred in both groups (18 NPTRC; 3 recurrences). The A/B versus C/D grouping yielded 81.3% sensitivity and 100% specificity. The ordinal TIC analysis yielded an area under the curve of 0.952. Interobserver agree-ment was high for the four TIC categories (Fleiss’ κ = 0.889). Conclusions: Type A was associated with NPTRC, Types C/D with recurrence, and Type B represented an indeterminate pattern. These descriptive findings require independent validation before clinical use.