BACKGROUND:Management of axillary nodes in breast cancer (BC) remains controversial. Increasingly, node-positive patients receive primary systemic therapy (PST), achieving axillary downstaging in up to 70% of cases. However, current imaging methods, despite being pivotal in the choice for PST, show limited accuracy in assessing treatment response. This study evaluated the diagnostic performance of hybrid [18F]FDG PET/MRI as non-invasive, single-step tool for post-PST nodal assessment. METHODS:This prospective, single-arm, monocentric interventional trial (SNBvsPET/MRI1, ClinicalTrials.gov NCT04826211) was conducted at San Raffaele Scientific Institute, Milan. Patients with node-positive BC eligible for PST were enrolled between September 2019 and December 2024. In addition to routine imaging, including axillary ultrasound (A-US), [18F]FDG PET/MRI was performed before and after PST. Scans were independently reviewed by two radiologists and two nuclear medicine physicians. Final pathology served as the reference standard. FINDINGS:Of 109 screened patients, 68 were included in the final analysis Mean(SD) age was 52.3(11.0) years. Residual axillary disease was pathologically confirmed in 30(44.2%) patients. [18F]FDG PET/MRI correctly identified 16 cases (sensitivity 53.3%, specificity 68.4%, PPV 57.1%, NPV 65.0%). Diagnostic accuracy varied by BC subtype with higher PPV in luminal (85.7%) and greater NPV in HER2+ and triple-negative tumors (83.3%). Overall, the performance of [18F]FDG PET/MRI and A-US were not significantly different (p > 0.05). INTERPRETATIONS:[18F]FDG PET/MRI accuracy for axillary staging in node-positive BC patients following PST is limited. Our findings are hypothesis-generating to design future trials and suggest that tailoring imaging to molecular subtype may optimize axillary evaluation and better inform surgical decision-making after PST.

IntroductionAccurately predicting pathological complete response (pCR) after primary systemic therapy (PST) in breast cancer remains a clinical challenge. This study compares the diagnostic performance of ultrasound (US) and Fluorodeoxyglucose positron emission tomography/magnetic resonance imaging ([18F]FDG PET/MRI) in predicting breast-pCR following PST.MethodsThis multicenter analysis included 143 patients: 54 node-positive patients from San Raffaele Hospital, who underwent an additional [18F]FDG PET/MRI within a prospective trial (ClinicalTrials.gov ID: NCT04826211) and 89 cases retrospectively retrieved from the database of Heidelberg Hospital, irrespectively of nodal status at diagnosis. In US, breast clinical complete response (breast cCR) was defined as a tumor size of 0 mm or no sign of tumor in the breast; in [18F]FDG PET/MRI, as the absence of significant [18F]FDG uptake on PET images and contrast-enhancement on MRI. Diagnostic accuracy was assessed across PET only, MRI only, combined PET/MRI (PET or MRI positive), and concordant PET/MRI (both positive). Subgroup analyses explored associations of breast cCR with tumor molecular subtypes.Results[18F]FDG PET/MRI showed a sensitivity of 62% (95% CI 42%-81%) and a specificity of 67% (95% CI 46%-83%), whereas ultrasound showed a sensitivity of 59% (95% CI 44%-73%) and a specificity of 62% (95% CI 46%-77%) in detecting breast response to PST. No significant difference was observed between [18F]FDG PET/MRI and US in terms of sensitivity (62.9%vs59.1%, p=0.93) and specificity (66.6%vs62.2%, p=0.94) in detecting response to PST. Exploratory subgroup analysis suggested variation in sensitivity: US showed a sensitivity of 73% (95% CI 0.45-0.92) in triple-negative tumors and 50% (95% CI 16%-84%) in HER2-positive tumors, while [18F]FDG PET/MRI demonstrated a sensitivity of 77% (95% CI 46%-95%) in Luminal B cancers.Conclusion[18F]FDG PET/MRI and US showed comparable performance in diagnostic accuracy of breast pCR following PST, with varying effectiveness across tumor subtypes. Further research should focus on multimodal imaging strategies integrated with clinical and molecular data.

Breast cancer (BC) requires the evaluation of tumor aggressiveness features to guide treatment decisions. Biopsy-derived prognostic information may differ from surgical histopathology due to tumor heterogeneity. Hybrid PET/MRI can provide additional information for tumor characterization, supporting initial therapy planning and prognosis. In this work, we acquired 157 BC patients using a hybrid PET/MRI scanner. The PET data were combined with ADC and semi-quantitative DCE-MRI metrics to derive “hybrid PET/MRI parameters.” Pathological data such as tumor grade, hormone receptors, proliferation index (Ki67), and surrogate molecular subtype were collected, and we evaluated their associations with hybrid imaging, also comparing with the PET and MRI data analyzed separately. Ki67 showed moderate correlations with PET, ADCmin, and most hybrid parameters. The PET and hybrid data differentiate histopathological factors, while ADCmin differentiates G1 vs. G2 and luminal A vs. luminal B. In the ROC analysis, hybrid SUVmax/ADCmin shows better performance to predict luminal B from luminal A (AUC 0.720, sensitivity 73.1%, specificity 63.2%, PPV 54.3%, NPV 79.7%) than SUVmean alone. Our findings suggest that these novel hybrid PET/MRI parameters may help the characterization of tumor tissue in IDC. However, a multivariate analysis is needed to confirm our preliminary results.

IntroductionAccurate staging at diagnosis is essential for optimizing treatment strategies and prognosis in early breast cancer (EBC). [18F]FDG positron emission tomography/magnetic resonance imaging (PET/MRI) is a hybrid imaging modality that enables simultaneous evaluation of locoregional disease and metastatic spread. This study assessed the impact of [18F]FDG PET/MRI on treatment planning in patients with EBC.MethodsThis unplanned sub-study derives from a prospective, interventional, single-arm clinical trial (SNB vs PET/MRI 2) conducted at San Raffaele University Hospital (Milan) between July 2020 and April 2024 (NCT04829643). Patients with EBC scheduled for primary surgery underwent additional preoperative [18F]FDG PET/MRI. The primary endpoint was the proportion of patients whose treatment strategy was modified based on PET/MRI findings. The secondary endpoint was the performance of PET/MRI in detecting multifocal breast cancer compared with standard imaging.ResultsA total of 264 patients, including five bilateral cases, were analyzed. [18F]FDG PET/MRI led to treatment plan modifications in 30.7% of patients. Surgical approach was altered in 23.9%, while 4.9% received primary systemic therapy and 1.9% were referred for systemic therapy alone. PET/MRI showed a sensitivity of 61.7%, specificity of 84.9%, positive predictive value (PPV) of 49.1%, and negative predictive value (NPV) of 90.4% for multifocal disease detection. When combined with standard imaging, specificity and PPV increased to 96.0% and 63.6%, respectively (p=0.001). Multifocal tumors detected by PET/MRI accounted for 15.2% of the cohort.Conclusions[18F]FDG PET/MRI significantly influences treatment decisions in EBC, modifying management in nearly one-third of patients. However, its moderate diagnostic accuracy warrants caution to prevent overtreatment.

To identify a tumor-mean absorbed dose (Dmean) that can predict response to Yttrium-90 resin-microsphere transarterial radioembolization (TARE) in patients with hepatocellular carcinoma (HCC) and evaluate its efficacy and safety. Patients with HCC eligible for TARE in two centers between January 2020 and May 2024 were retrospectively analyzed. Clinical, radiological, and procedural data were collected. Objective response rate (ORR) on lesion, complete response (CR), overall response, time-to-local progression (TLP), and time-to-progression (TTP) were evaluated on contrast-enhanced CT at 3 and 6 months according to mRECIST. The optimal Dmean of ORR on the target lesion and of CR was identified with ROC analysis at 3-months. Fischer’s test compared ORR, Kaplan–Meier survival outcomes, and Cox regression was used for uni-and multivariable analyses. Seventy-six lesions in 64 patients (mean age 71.3 ± 9.6; 54 men) were evaluated. Median follow-up was 15.0 months (IQR 8.0–24.3). Mean tumor diameter was 55.2 (± 31.8) mm. CR on target lesion at 3-months was achieved in 42 lesions. Mean TLP and OS were 27.6 ± 2.5 and 36.2 ± 2.9 months, respectively. The calculated Dmean for ORR was 296.74 Gy (specificity 100, PPV 100

Personalized treatment schemes are being systematically applied to ensure best treatment outcome in oncologic patients. This is true also for personalized dosimetry in transarterial radioembolization (TARE) in hepatocellular carcinoma (HCC) patients. Precise and detailed volumetric and functional data derived from radiological and nuclear imaging methods are essential for personalized dosimetry. We sought to evaluate accuracy of dual-phase cone-beam CT (CBCT) in comparison to pre-treatment contrast-enhanced CT (CECT), and 99mTc-macroaggregated albumin-SPECT/CT ([99mTc]MAA SPECT/CT) to predict and assess the efficacy of TARE based on post-treatment 90Y PET/CT. Thirty consecutive patients with HCC treated with TARE were included. Intraprocedural dual-phase CBCT acquisition protocol was developed to distinguish tumor volume in the early arterial phase and perfused volume of non-affected liver in the late arterial phase. Volumetric data obtained from pre-treatment CECT, dual-phase CBCT and [99mTc]MAA SPECT/CT were compared to post-treatment 90Y PET/CT considered the standard reference. Treatment simulations for final calculated dose from the different imaging derived volumes were then compared to post-treatment 90Y PET/CT. CBCT resulted as the most accurate method in predicting tumor- (R2 0.88) and perfused volumes (R2 0.82). Dosimetry prediction planning performed on derived volumes from the different methods did not show significant difference (p < 0.05), yet highest concordance with 90Y PET/CT data was observed with dual-phase CBCT. Our study shows that dual-phase CBCT acquisition is a novel alternative method for correctly and safely administering more accurate and defined doses during TARE. clinicaltrials.gov ID: NCT03981497.

Accurate identification of lymph node (LN) metastases is pivotal for surgical planning of pancreatic neuroendocrine tumours (PanNETs); however, current imaging techniques have sub-optimal diagnostic sensitivity. Aim of this study is to investigate whether [68Ga]Ga-DOTATOC PET radiomics might improve the identification of LN metastases in patients with non-functioning PanNET (NF-PanNET) referred to surgical intervention. Seventy-two patients who performed preoperative [68Ga]Ga-DOTATOC PET between December 2017 and March 2022 for NF-PanNET. [68Ga]Ga-DOTATOC PET qualitative assessment of LN metastases was measured using diagnostic balanced accuracy (bACC), sensitivity (SN), specificity (SP), positive and negative predictive values (PPV, NPV). SUVmax, SUVmean, Somatostatin receptor density (SRD), total lesion SRD (TLSRD) and IBSI-compliant radiomic features (RFs) were obtained from the primary tumours. To predict LN involvement, these parameters were engineered, selected and used to train different machine learning models. Models were validated using tenfold repeated cross-validation and control models were developed. Models’ bACC, SN, SP, PPV and NPV were collected and compared (Kruskal–Wallis, Mann–Whitney). LN metastases were detected in 29/72 patients at histology. [68Ga]Ga-DOTATOC PET qualitative examination of LN involvement provided bACC = 60

Purpose: The early regression index (ERI) predicts treatment response in rectal cancer patients. Aim of current study was to prospectively assess tumor response to neoadjuvant chemo-radiotherapy (nCRT) of locally advanced esophageal cancer using ERI, based on MRI. Material and methods: From January 2020 to May 2023, 30 patients with esophageal cancer were enrolled in a prospective study (ESCAPE). PET-MRI was performed: i) before nCRT (t(pre)); ii) at mid-radiotherapy, t(mid); iii) after nCRT, 2-6 weeks before surgery (t(post)); nCRT delivered 41.4 Gy/23fr with concurrent carboplatin and paclitaxel. For patients that skipped surgery, complete clinical response (cCR) was assessed if patients showed no local relapse after 18 months; patients with pathological complete response (pCR) or with cCR were considered as complete responders (pCR + cCR). GTV volumes were delineated by two observers (V-pre, V-mid, V-post) on T2w MRI: ERI and other volume regression parameters at t(mid) and t(post) were tested as predictors of pCR + cCR. Results: Complete data of 25 patients were available at the time of the analysis: 3/25 with complete response at imaging refused surgery and 2/3 were cCR; in total, 10/25 patients showed pCR + cCR (pCR = 8/22). Both ERImid and ERIpost classified pCR + cCR patients, with ERImid showing better performance (AUC:0.78, p = 0.014): A two-variable logistic model combining ERImid and V-pre improved performances (AUC:0.93, p < 0.0001). Inter-observer variability in contouring GTV did not affect the results. Conclusions: Despite the limited numbers, interim analysis of ESCAPE study suggests ERI as a potential predictor of complete response after nCRT for esophageal cancer. Further validation on larger populations is warranted.

Sentinel lymph node biopsy (SLNB) is currently considered as a viable alternative to elective neck dissection (END) for the management of cN0 oral cavity squamous cell carcinoma (OCSCC). However, some difficulties were detected in sentinel lymph node (SLN) identification in floor of mouth (FOM) and ventral tongue tumors because of the so-called “shine-through radioactivity” of the injection site, which may mask nodal hotspots in proximity. We assessed the feasibility and the potential strengths of combining 99mTc-Tilmanocept with indocyanine green (ICG) fluorescence lympho-angiography in a dedicated multimodal protocol for SLNB in T1/T2N0 oral cancer to evaluate the synergistic role of each of these two tracers in providing the appropriate sensitivity and ease of learning, even in such a critical anatomical subsite. A detailed, stepwise description of our multimodal protocol is provided, together with the presentation of its application in two cases of early-stage ventral tongue tumors. Radioactive guidance with 99mTc-Tilmanocept was used preoperatively to perform planar lymphoscintigraphy and single-photon emission computed tomography/computed tomography and to define the nodal hotspot(s) and the surgical “roadmap”. In addition, it was used intraoperatively to pinpoint the SLN location within each nodal hotspot with high specificity but limited spatial resolution. Optical guidance with ICG injection at the tumor bed and near-infrared fluorescence imaging was then added, providing intuitive intraoperative guidance within each nodal hotspot with high spatial resolution. Our small experience with this protocol is illustrated and future perspectives are highlighted.

Background: Accurate staging is crucial in breast cancer (BC) management and could potentially improve prognosis. Recent studies reported that PET/ MRI is a novel hybrid imaging tool which provides a simultaneous assessment of locoregional extent and metastatic spread. This study evaluated the impact on BC management of FDG PET/MRI at diagnosis in patients who were candidates for primary surgery.

Abstract Background: Breast cancer (BC) staging is essential to planning the most appropriate treatment pathway. Currently, BC management has become more tailored to the tumor’s and patient’s characteristics. However, BC imaging shows varying performance according to tumor subtypes. In particular, routine imaging may pose some challenges when evaluating luminal A BC (LumA) and lobular BC (Lob). LumA, due to low grade and proliferation index (< 20%) shows lower sensitivity on axillary US, reduced MRI enhancement, and low FDG-avidity on PET. Similarly, Lob, due to its peculiar single-cell growth pattern, exhibits inferior sensitivity on axillary MRI and FDG-avidity. LumA and Lob account for >50% of all BCs. Despite their favourable prognosis, metastases and recurrences still occur; this translates into a higher absolute number of events than in other subtypes. As a result, a concrete risk of disease underestimation and under-treatment exists. Two ongoing studies on FDG-PET/MRI imaging in our institution have already demonstrated that its sensitivity also decreases in LumA and Lob. Based on these premises, our hypothesis states that by combining the advantages of hybrid PET/MRI with the high accuracy of 16α -18F-fluoro-17-beta-estradiol(FES), a radiolabeled form of estrogen binding to functionally active ER, we could obtain a reliable, non-invasive, operator-independent, one-stage imaging method for staging LumA and ER-positive Lob. Trial design: This is a prospective cohort study where patients with LumA and ER-positive Lob will be enrolled in four cohorts undergoing: A) primary surgery; B) induction endocrine therapy; C) neoadjuvant chemotherapy, and D) systemic therapy for metastatic disease. FES PET/MRI examinations will be performed at baseline for local and systemic staging in all cohorts and a second exam after systemic therapy in cohorts C-D. Correlations between the FES PET/MRI parameters and pathology, gene expression, and FDG PET parameters, when available, will be investigated. Study aims will evaluate: 1) the performance of the FES PET/MRI in axillary staging compared with axillary surgery; 2) potential correlations between changes in FES uptake and changes in proliferation index after three weeks of endocrine therapy (ET); 3) the performance of the FES PET/MRI in systemic staging of patients undergoing systemic therapy in comparison with standard imaging; 4) biological determinants of tumor heterogeneity on pathological, imaging, and genomic levels. Statistics: The primary analysis in cohort A will test the sensitivity of the FES PET/MRI in detecting macrometastatic axillary nodes. Assuming that the probability that a patient has positive nodes is 33%, 119 patients (10% drop-out included) will provide 80% power to reject the null hypothesis about sensitivity at a 5% significance level if the true sensitivity is at least 50%. Results from the FES PET/MRI will be also compared with standard imaging in terms of sensitivity and number of lesions detected using the Mc-Nemar test for paired proportions and the Wilcoxon signed-rank test for paired data. The primary analysis in Cohort B will test the association between the FES-SUV change from pre-ET to post-ET and the Ki-67 change from core biopsy to post-ET in ER positive BC patients with a Ki-67 >10%. The association between these changes will be measured by the Pearson correlation index ρ. Α total of 52 patients (10% drop-out included) from Cohort B will provide 80% power to reject the null hypothesis about ρ at a 5% significance level if the true ρ is at least 0.4. No formal sample size was calculated for cohort C and D: results will be considered descriptive in nature, informing sample size considerations for future trials. We intent to recruit 20 and 30 patients, respectively. Accrual has not started yet. Project funded by AIRC (Associazione Italiana Ricerca sul Cancro) Next Gen Clinician Scientist ID 28378 Contact: Dr. Rosa Di Micco, dimicco.rosa@hsr.it Citation Format: Rosa Di Micco, Carla Canevari, Francesca Gallivanone, Nicole Rotmensz, Veronica Zuber, Sara Baleri, Giovanni Cisternino, Mario Rampa, Stefania Zambelli, Giulia Viale, Patrizia Zucchinelli, Manuela Morgante, Paola Scifo, Elena Venturini, Paola Magnani, Isabella Sassi, Vincenzo Bagnardi, Pietro Panizza, Giampaolo Bianchini, Arturo Chiti, Oreste Davide Gentilini. FES-PET/MRI for Tailored treatment of luminal A and lobular breast cancer: a prospective cohort study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-19-03.

Background: Breast cancer (BC) management has evolved towards a tailored treatment mainly based on tumor and patient's characteristics. Staging at diagnosis is crucial but imaging performance is not equivalent in all subtypes. In particular, staging luminal A BC (LumA) and lobular BC (Lob) remains complex. Despite the relatively favourable prognosis, nodal metastases and recurrence are possible and, as LumA and Lob account for >50% of all BCs, their absolute values are high with a concrete risk of disease underestimation and undertreatment. Genomic testing showed that a high genomic risk of recurrence could be hidden behind low clinical risk tumors. To date, obtaining an initial reliable staging of LumA and Lob in order to plan the most appropriate treatment and to minimize the recurrence risk represents an unmet clinical need. In San Raffaele Hospital (OSR), two ongoing studies on FDG-PET/MRI in BC staging showed that its sensitivity decreases in these BC types. Our hypothesis is that combining the advantages of hybrid PET/MRI and the high accuracy of 16- alpha-18F-fluoro-17-beta-estradiol(FES), a radiolabeled form of estrogen binding to functionally active ER, we could obtain a reliable, non-invasive, operator-independent, one-stage imaging method.

To evaluate the role of 68Ga-DOTATOC PET parameters in predicting DAXX/ATRX loss of expression in patients with Pancreatic neuroendocrine tumors (PanNET) candidate to surgery. This retrospective study included 72 consecutive patients with PanNET (January 2018–March 2022) who underwent to 68Ga-DOTATOC PET for preoperative staging. Image analysis: qualitative assessment and extraction of SUVmax, SUV mean, somatostatin receptor density (SRD), and total lesion somatostatin receptor density (TLSRD) from primary PanNET. Radiological diameter and biopsy information (grade, Ki67) were collected. Loss of expression (LoE) of DAXX/ATRX was assessed by immunohistochemistry on surgical specimen. Student t-test, univariate and multivariate logistic regression and ROC curves have been used to investigate the predictive value of PET parameters on DAXX/ATRX LoE. Forty-two/72 patients had a G1, 28/72 a G2, and 2/72 a G3 PanNET. Seven/72 patients had DAXX LoE, 10/72 ATRX LoE, and 2/72 DAXX/ATRX LoE. SRD and TLSRD could predict DAXX LoE (p = 0.002, p = 0.018, respectively). By evaluating SRD in combination with radiological diameter, only SRD maintained statistical significance (multivariate logistic regression: p = 0.020, OR = 1.05), providing the best prediction (AUC-ROC = 79.01