We investigated whether we could identify a panel of miRNAs associated with response to treatment in tumor tissues of patients with Hormone Receptor-positive/HER2-negative metastatic breast cancer treated with endocrine therapy (ET) and the CDK4/6 inhibitor (CDK4/6i)i palbociclib. In total, 52 patients were evaluated, with 41 receiving treatment as the first line. The overall median PFS was 20.8 months (range 2.5–66.6). In total, 23% of patients experienced early progression (<6 months). Seven miRNAs (miR-378e, miR-1233, miR-99b-5p, miR-1260b, miR-448, -miR-1252-5p, miR-324-3p, miR-1233-3p) showed a statistically significant negative association with PFS. When we considered PFS < 6 months, miR-378e, miR-99b-5p, miR-877-5p, miR-1297, miR-455-5p, and miR-4536-5p were statistically associated with a poor outcome. In the multivariate analysis, the first three miRNAs confirmed a significant and independent impact on PFS. The literature data and bioinformatic tools provide an underlying molecular rationale for most of these miRNAs, mainly involving the PI3K/AKT/mTOR pathway and cell-cycle machinery as cyclin D1, CDKN1B, and protein p27^Kip1 and autophagy. Our findings propose a novel panel of miRNAs associated with a higher likelihood of early progression in patients treated with ET and Palbociclib and may contribute to shed some light on the mechanisms of de novo resistance to CDK4/6i, but this should be considered exploratory and evaluated in larger cohorts.

Background/Objectives: Assessing treatment response in neuroendocrine tumors (NETs) remains challenging. The multifactorial mechanism of action of peptide receptor radionuclide therapy (PRRT) further complicates response evaluation, particularly in the absence of standardized criteria. This study aimed to compare different imaging-based response assessment methods after PRRT and to explore their relationship with clinical outcomes, particularly progression-free survival (PFS). Methods: In this single-center retrospective study, we analyzed NET patients treated with PRRT between 2020 and 2024 who underwent [⁶⁸Ga]Ga-DOTATOC PET/CT before and after therapy, with a minimum follow-up of 12 months. Five response criteria were evaluated: (a) Krenning Score changes; (b) adapted PERCIST criteria (MORE); (c) ZP-normalized parameter; (d) qualitative visual PET assessment; and (e) RECIST-based morphological response on contrast-enhanced CT. Imaging findings were correlated with clinical outcomes. Nonparametric analyses were performed using the MedCalc^® software. Results: Thirty-one patients (median age 63 years; 17 males) with NET were evaluated after PRRT. Post-PRRT PET/CT was performed at a median of 3 months. Response rates varied across methods, with higher rates noted using functional imaging (MORE 66%, Visual PET 68%, ZP 70%) compared to RECIST (40%) and Krenning score (21%). After a median follow-up of 37 months, 58% of patients experienced disease progression. Although no significant association was found between the response criteria and progression (p > 0.05), functional imaging showed a trend toward better correlation with longer progression-free survival. Conclusions: Functional PET-based responsecriteria suggest association with progression-free survival compared to RECIST criteria and Krenning score changes. However, given the exploratory nature of the study and its methodological limitations, these observations should be considered hypothesis-generating only. They do not provide definitive evidence of superiority over established assessment methods and therefore should not be interpreted as practice-changing.

Background/Objectives: The extensive use of computed tomography (CT) has led to a significant increase in the detection of small and non-palpable pulmonary nodules, necessitating the use of invasive methods for definitive diagnosis. Video-assisted thoracoscopic surgery (VATS) has become the preferred procedure for nodule resections; however, intraoperative localization remains challenging, especially for deep or subsolid lesions. This study explores whether SPECT/CT improves the technical and clinical outcomes of radio-guided occult lesion localization (ROLL) before uniportal video-assisted thoracoscopic surgery (u-VATS). Methods: This is a retrospective study involving consecutive patients referred for the resection of pulmonary nodules who underwent CT-guided ROLL followed by u-VATS between September 2017 and December 2024. From January 2023, SPECT/CT was systematically added after planar imaging. The cohort was divided into a planar group and a planar + SPECT/CT group. The inclusion criteria involved nodules sized ≤ 2 cm, with ground glass or solid characteristics, located at a depth of <6 cm from the pleural surface. ^99mTc-MAA injected activity, timing, the classification of planar and SPECT/CT image findings (focal uptake, multisite with focal uptake, multisite without focal uptake), spillage, and post-procedure complications were evaluated. Statistical analysis was performed, with continuous data expressed as the median and categorical data as the number. Comparisons were made using chi-square tests for categorical variables and the Mann–Whitney U test for procedural duration. Cohen’s kappa coefficient was calculated to assess agreement between imaging modalities. Results: In total, 125 patients were selected for CT-guided radiotracer injection followed by uniportal-VATS. The planar group and planar + SPECT/CT group comprised 60 and 65 patients, respectively. Focal uptake was detected in 68 (54%), multisite with focal uptake in 46 (36.8%), and multisite without focal uptake in 11 patients (8.8%). In comparative analyses between planar and SPECT/CT imaging in 65 patients, 91% exhibited focal uptake, revealing significant differences in classification for 40% of the patients. SPECT/CT corrected the classification of 23 patients initially categorized as multisite with focal uptake to focal uptake, improving localization accuracy. The mean procedure duration was 39 min with SPECT/CT. Pneumothorax was more frequently detected with SPECT/CT (43% vs. 1.6%). The intraoperative localization success rate was 96%. Conclusions: SPECT/CT imaging in the ROLL procedure for detecting pulmonary nodules before u-VATs demonstrates a significant advantage in reclassifying radiotracer positioning compared to planar imaging. Considering its limited impact on surgical success rates and additional procedural time, SPECT/CT should be reserved for technically challenging cases. Larger sample sizes, multicentric and prospective randomized studies, and formal cost–utility analyses are warranted.