6120 Background: Sinonasal carcinomas (SNCs) are rare malignancies with poor prognosis. Multimodal treatments including induction chemotherapy (ICT), surgery and radiotherapy (RT) - modulated by histology and response to ICT - are often used, aiming to improve oncological outcome in terms of local control and survival. Two phase II clinical studies published in 2023 assessed the role of ICT in SNCs, SINTART1 and 2 for resectable and unresectable tumors, respectively [PMIDs: 37164774, 37163806]. The current work aims at reporting the long-term follow-up (FUP) data for both trials. Methods: The FUP was updated as of January 2026 for patients enrolled in both clinical studies. Median FUP was estimated with reverse Kaplan-Meier method. The following survival times were analyzed with Kaplan-Meier method in each cohort: overall survival (OS), disease-free survival (DFS), loco-regional-free survival (LRFS), distant metastasis-free survival (DMFS). Results: The updated median (m) survival times (in months) with their 95% confidence intervals (CI) and the event rates are detailed in Table 1. Pooling together the 2 studies, 30% of patients (18/60) were alive at last follow-up. Conclusions: SINTART 1 and 2 represent, to date, the largest prospective cohorts with long-term survival data in SNCs. With a median FUP exceeding 9 years, these results provide a robust benchmark for ICT-based multimodal strategies in this setting. Survival outcomes remain consistent with the initial reports, indicating that prognosis is largely determined within the first 2-3 years, when most deaths occur (approximately 70%). The near-overlap of mDFS and mLRFS identifies loco-regional failure as the predominant pattern of recurrence. Moreover, the short interval between relapse and death underscores the limited opportunity for salvage. These findings collectively emphasize the need for more effective local-intensification approaches and novel systemic agents. Additional analyses are underway to identify prognostic and predictive factors. Clinical trial information: NCT02099175 ; NCT02099188 . Resectable (SINTART1)N=35 Unresectable (SINTART2)N=25 mFUP (95% CI) 108.26 (97.37-129.84) 103.22 (91.68-NR) mOS (95% CI)Events 37.53 (21.97-98.36)66% 27.07 (11.28-65.03)76% mDFS (95% CI)Events 26.25 (15.43-80.43)71% 17.1 (7.89-37.76)80% mLRFS (95% CI)Events 26.25 (15.43-80.43)71% 18.95 (7.89-39.05)80% mDMFS (95% CI)Events 34.47 (21.84-96.32)69% 26.88 (9.31-46.78)76%

Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are commonly treated with radio-ligand therapy (RLT) but reliable biomarkers for predicting early disease progression are lacking. In this exploratory study we investigated whether microRNA (miRNA) expression in archival samples is associated with early response to RLT and with tumour origin and grading. Forty-eight formalin-fixed, paraffin-embedded samples from G1–G2 GEP-NETs patients treated with RLT (177Lu-Oxodotreotide (Lutathera®) were analyzed. Two CT or MRI scans per patient, performed within three months before and after RLT, were used to assess early progression (PD) according to RECIST v1.1. Thirteen miRNAs previously implicated in NET biology were quantified by qRT-PCR. Multiple logistic regression evaluated associations between miRNA expression and early progression, as well as relationships with tumour origin and grade. We observed trends suggesting that lower expression of miR-21-5p (OR = 0.51, 90% CI: 0.26–1.00) and miR-196a (OR = 0.78, 90% CI: 0.59–1.02), and higher expression of miR‑30a-5p (OR = 2.62, 90% CI: 0.1.14–6.05) may be associated with a reduced likelihood of early progression. Lower miR-196a and higher miR‑30a-5p expression was also more frequent in pancreatic tumours and lower miR-196a expression is associated to G1 lesions. These findings indicate that miRNA profiling in GEP-NETs archival samples is feasible and support the potential role of miR-21-5p, miR-196a, and miR‑30a-5p as exploratory biomarkers for early progression afterRLT. Further validation in independent cohorts is required to confirm these preliminary observations.

Relapsed/metastatic anaplastic thyroid carcinoma (R/M ATC) is associated with poor prognosis. Approximately 40

OBJECTIVE:For patients with muscle-invasive bladder cancer (MIBC), accurate assessment of neoadjuvant therapy response may allow for bladder-sparing strategies, emphasizing the need for accurate, noninvasive response assessment. Multi-parametric magnetic resonance imaging (mpMRI) has emerged as a promising imaging modality, but its reproducibility and diagnostic performance following neoadjuvant immunotherapy remain underexplored. METHODS:We analyzed data from 115 patients across three prospective trials (NABUCCO, TURANDOT, and PURE-01). Patients underwent mpMRI after transurethral resection of bladder tumor and before neoadjuvant immunotherapy, and after neoadjuvant immunotherapy prior to radical cystectomy. Multiple radiologists assessed the radiological response using qualitative (AJCC Staging, nacVI-RADS, Visual Response, and RECIST 1.1) and quantitative (diameter, volumetric) criteria. Using Fleiss' kappa, Krippendorff's alpha, and intraclass-correlation coefficient (ICC), we assessed inter-radiologist variability. ROC-AUC (Receiver operator characteristic-area under the curve) assessed the diagnostic accuracy for pathological complete response (pCR) of the primary tumor, with correlations explored for circulating tumor (ctDNA) and tumor cell density. RESULTS:Visual assessment demonstrated high inter-radiologist agreement among qualitative methods (α = 0.79, 95% CI: [0.68-0.87]), while semi-automatic volumetric analysis showed high reproducibility and accuracy quantitatively (ICC = 0.93, 95% CI: [0.83-0.95], AUC = 0.8-0.98). Volumetric measurements showed moderate correlation with ctDNA and tumor cell density. All methods exhibited strong predictive performance for pCR, but longitudinal volume changes showed a good combination of reproducibility and accuracy. CONCLUSIONS:Semi-automatic volumetric mpMRI assessment is a reproducible and accurate tool for evaluating local response to neoadjuvant immunotherapy in MIBC. Despite focusing on the primary tumor, these findings support its potential as an imaging biomarker and foundation for future response criteria. However, confirming its role in clinical decision-making requires prospective validation.

OBJECTIVE:This study aims to identify the best response criteria in patients with sinonasal cancer undergoing induction chemotherapy (IC). MATERIAL AND METHODS:Patients enrolled in SINTART-1 and SINTART-2 were included in this study. Unidimensional diameters (anteroposterior, AP; laterolateral, LL; craniocaudal, CC), maximum axial area (Amax), and volume (V) were performed on MRI by two radiologists. RECIST 1.1 assessment was included as a categorical variable. Variables were evaluated at baseline, after the 1st chemotherapy cycle, and at the best response. Interobserver repeatability was analyzed. Stepwise univariable and multivariable Cox proportional-hazards regression models were used to correlate variables with Disease-Free Survival (DFS) and Overall Survival (OS). RESULTS:60 patients were included in this study. Interobserver correlation coefficient at baseline and after 1st IC cycle was excellent for V (0.916 and 0.928 respectively), CC diameter (0.96 and 0.863), and AP diameter (0.846 and 0.796), good for LL diameter, and moderate for Amax. RECIST 1.1 criteria after the 1st IC cycle and at best response were not associated with OS and DFS. Volume variation after the 1st IC cycle and at best response was significantly associated with OS (p < 0.0001 and p = 0.002) and DFS (p < 0.0001 and p = 0.005). At the multivariable analysis, V variation after the 1st IC cycle and at best response was the only variable significantly associated with OS (p < 0.001 and p = 0.0019) and DFS (p = 0.0004 and p = 0.004). CONCLUSIONS:Volume variation should be preferred to RECIST 1.1 and other measurements to describe the radiological response to IC in sinonasal cancers.

INTRODUCTION:Despite several therapeutic efforts, lung cancer remains a highly lethal disease. Novel therapeutic approaches encompass immune-checkpoint inhibitors, targeted therapeutics and antibody-drug conjugates, with different results. Several studies have been aimed at identifying biomarkers able to predict benefit from these therapies and create a prediction model of response, despite this there is a lack of information to help clinicians in the choice of therapy for lung cancer patients with advanced disease. This is primarily due to the complexity of lung cancer biology, where a single or few biomarkers are not sufficient to provide enough predictive capability to explain biologic differences; other reasons include the paucity of data collected by single studies performed in heterogeneous unmatched cohorts and the methodology of analysis. In fact, classical statistical methods are unable to analyze and integrate the magnitude of information from multiple biological and clinical sources (eg, genomics, transcriptomics, and radiomics).METHODS AND OBJECTIVES:APOLLO11 is an Italian multicentre, observational study involving patients with a diagnosis of advanced lung cancer (NSCLC and SCLC) treated with innovative therapies. Retrospective and prospective collection of multiomic data, such as tissue- (eg, for genomic, transcriptomic analysis) and blood-based biologic material (eg, ctDNA, PBMC), in addition to clinical and radiological data (eg, for radiomic analysis) will be collected. The overall aim of the project is to build a consortium integrating different datasets and a virtual biobank from participating Italian lung cancer centers. To face with the large amount of data provided, AI and ML techniques will be applied will be applied to manage this large dataset in an effort to build an R-Model, integrating retrospective and prospective population-based data. The ultimate goal is to create a tool able to help physicians and patients to make treatment decisions.CONCLUSION:APOLLO11 aims to propose a breakthrough approach in lung cancer research, replacing the old, monocentric viewpoint towards a multicomprehensive, multiomic, multicenter model. Multicenter cancer datasets incorporating common virtual biobank and new methodologic approaches including artificial intelligence, machine learning up to deep learning is the road to the future in oncology launched by this project.

In Peptide Receptor Radionuclide Therapy (PRRT) with [177Lu]Lu-DOTATATE of gastro-entero-pancreatic neuroendocrine tumours (GEP NETs) a question remains open about the potential benefits of personalised dosimetry. This observational prospective study examines the association of individualized dosimetry with progression free survival (PFS) in G1-G2 GEP NETs patients following the standard [177Lu]Lu-DOTATATE therapeutic regimen. The analysis was conducted on 42 patients administered 4 times, and on 165 lesions. Dosimetry was performed after the first and the forth cycle, with two SPECT/CT scans at day 1 and 7 after administration. Global mean Tumour absorbed Dose of each patient (GTD) was calculated after cycle 1 and 4 as the sum of lesion doses weighted by lesion mass, normalized by the global tumour mass. Cumulative GTD_TOT was calculated as the mean between cycle 1 (GTD_1) and 4 (GTD_4) multiplied by 4. Patients were followed-up for median 32.8 (range 18–45.5) months, through blood tests and contrast enhanced CT (ceCT). This study assessed the correlation between global tumour dose (GTD) and PFS longer or shorter than 24 months. After a ROC analysis, we stratified patients according to the best cut-off value for two additional statistical analyses. At last a multivariate analysis was carried out for PFS > / < 24 months. The median follow-up interval was 33 months, ranging from 18 to 45.5 months. The median PFS was 42 months. The progression free survival rate at 20 months was 90.5

Background An accurate method of assessing the response of muscle-invasive bladder cancer (MIBC) to neoadjuvant treatment is needed for selecting candidates for bladder-sparing strategies. Purpose To evaluate the diagnostic accuracy and reproducibility of neoadjuvant chemotherapy Vesical Imaging Reporting and Data System (nacVI-RADS) scores and posttreatment Vesical Imaging Reporting and Data System (VI-RADS) scores when assessing MIBC response to neoadjuvant immunotherapy with multiparametric MRI (mpMRI). Materials and Methods A retrospective analysis of MRI scans was conducted in patients enrolled in the PURE-01 study (NCT02736266) from February 2017 to December 2019 who underwent pre- and postimmunotherapy mpMRI before radical cystectomy. Five readers independently reviewed the scans using VI-RADS and nacVI-RADS criteria. Diagnostic accuracy was evaluated for each reader, and the final histopathologic diagnosis served as the reference standard. Interreader agreement was assessed with the percentage of agreement, Conger κ, and Gwet agreement coefficient AC1. Results A total of 110 patients (median age, 67 years [IQR: 61-74]; 96 male) with 220 MRI scans were included; 80 (73%) patients had pure urothelial carcinoma. A total of 46 of 110 (42%) patients achieved a complete pathologic response. The sensitivity, specificity, and negative predictive value of nacVI-RADS 3 or higher for detecting residual disease (higher than stage ypT0) at radical cystectomy were 67%-84%, 63%-96%, and 63%-75%, respectively; for residual muscle-invasive disease (higher than stage ypT1), these values were 91%-98%, 55%-94%, and 93%-98%, respectively. The accuracy of nacVI-RADS was 72%-81% for stage ypT0 or higher disease and 71%-95% for stage ypT1 or higher disease. The accuracy of VI-RADS 3 or higher was 80%-95% for stage ypT1 or higher disease. The percentage of agreement for nacVI-RADS scores was 82% (κ = 0.62-0.65; AC1 = 0.65). Conclusion The nacVI-RADS scores showed good accuracy and reproducibility when assessing MIBC response to neoadjuvant immunotherapy. © RSNA, 2024 Supplemental material is available for this article.

This study aims to assess the predictive capability of cylindrical Tumor Growth Rate (cTGR) in the prediction of early progression of well-differentiated gastro-entero-pancreatic tumours after Radio Ligand Therapy (RLT), compared to the conventional TGR. Fifty-eight patients were included and three CT scans per patient were collected at baseline, during RLT, and follow-up. RLT response, evaluated at follow-up according to RECIST 1.1, was calculated as a percentage variation of lesion diameters over time (continuous values) and as four different RECIST classes. TGR between baseline and interim CT was computed using both conventional (approximating lesion volume to a sphere) and cylindrical (called cTGR, approximating lesion volume to an elliptical cylinder) formulations. Receiver Operating Characteristic (ROC) curves were employed for Progressive Disease class prediction, revealing that cTGR outperformed conventional TGR (area under the ROC equal to 1.00 and 0.92, respectively). Multivariate analysis confirmed the superiority of cTGR in predicting continuous RLT response, with a higher coefficient for cTGR (1.56) compared to the conventional one (1.45). This study serves as a proof of concept, paving the way for future clinical trials to incorporate cTGR as a valuable tool for assessing RLT response.

687 Background: As components of the liquid biopsy, Extracellular Vesicles (EVs) have gained major interest as biomarkers of diagnosis, prognosis and prediction of response/resistance to cancer therapies. Here we investigated if plasma EV immune profile, size and concentration in concert with plasma proteomics might discriminate responding from non-responding patients affected by advanced urothelial carcinoma (UC) or non-UC variant histologies (VH) undergoing cabozantinib (CABO) plus Durvalumab (DURVA) combination therapy after platinum chemotherapy (NCT03824691). Methods: We evaluated 40 patients for their plasma EV profile at baseline and at the first reassessment after 2-4 months of therapy. Baseline samples of 50 patients (40 plus additional 10 patients) were evaluated for their predictive potential. EVs were profiled using modified MACSplex technology (Miltenyi Biotec) coupled with flow cytometry and nanoparticle tracking analysis (NTA). Whole plasma was also searched for further indicators of response/resistance by proteomics (92 analytes, Immune-oncology panel, Olink). Results: Preliminary analysis of the single EV markers measuredin baseline samples evidenced no major association with response, although patients with VH histology showed a significant enrichment of CD1c and CD14 expressing EVs. Upon inclusion in the analysis of the on-therapy time point we were able to detect in the whole case set an increase of immune markers, including CD14, CD1c, CD2, CD20, CD8 and CD69; EV markers CD9, CD63 and CD81; platelet markers CD29, CD31 and CD326. This was also reflected by the global distribution of EV markers, which evidenced unexpectedly high levels of EVs exposing CD81 EV marker and CD8 already at baseline, with a further increase after therapy initiation. Finally, the dichotomization by response highlighted that a statistically significant increase of immune EVs was detectable almost exclusively in responding patients. NTA and plasma proteomics are currently ongoing. Conclusions: Our preliminary results suggest that the early dynamics in plasma EVs may inform on the clinical outcome to DURVA plus CABO. The significant increase of EVs expressing immune markers measured at first reassessment in responding patients may derive from the activation of the immune system induced by therapy. The comprehensive analysis of EV profiles, size and concentration together with plasma proteomics could give rise to predictive/prognostic biomarkers of response in this clinical setting, especially in patients with non-UC variant histologies. Acknowledgements. AIRC IG-25078 to VH, NET-2016-02361632 from Italian Health Ministry to A. Anichini. Clinical trial information: NCT03824691 .

BACKGROUND:The aim was to evaluate the performance of the Peritoneal Cancer Index (PCI) using imaging (ultrasound, contrast-enhanced computed tomography (CT), and whole-body diffusion-weighted magnetic resonance imaging (WB-DWI/MRI) in assessing peritoneal carcinomatosis and predicting non-resectability in tubo-ovarian carcinoma patients. METHODS:This was a prospective multicenter observational study. We considered all patients with suspected primary ovarian/tubal/peritoneal cancer who underwent preoperative ultrasound, CT, and WB-DWI/MRI (if available). The optimal cut off value for assessing the performance of the methods in predicting non-resectability was identified at the point at which the sensitivity and specificity were most similar. The reference standard to predict non-resectability was surgical outcome in terms of residual disease >1 cm or surgery not feasible. Agreement between imaging methods and surgical exploration in assessing sites included in the PCI score was evaluated using the Intraclass Correlation Coefficient (ICC). RESULTS:242 patients were included from January 2020 until November 2022. The optimal PCI cut-off for predicting non-resectability for surgical exploration was >12, which achieved the best AUC of 0.87, followed by ultrasound with a cut-off of >10 and AUC of 0.81, WB-DWI/MRI with a cut-off of >12 and AUC of 0.81, and CT with a cut-off of >11 and AUC of 0.74. Using ICC, ultrasound had very high agreement (0.94) with surgical PCI, while CT and WB-DWI/MRI had high agreement (0.86 and 0.87, respectively). CONCLUSION:Ultrasound performed by an expert operator had the best agreement with surgical findings compared to WB-DWI/MRI and CT in assessing radiological PCI. In predicting non-resectability, ultrasound was non-inferior to CT, while its non-inferiority to WB-DWI/MRI was not demonstrated.