Tumor Stiffness Measurement at Multifrequency MR Elastography to Predict Lymphovascular Space Invasion in Endometrial Cancer.

Background Pathologic lymphovascular space invasion (LVSI) is associated with poor outcome in endometrial cancer. Its relationship with tumor stiffness, which can be measured with use of MR elastography, has not been extensively explored. Purpose To assess whether MR elastography-based mechanical characteristics can aid in the noninvasive prediction of LVSI in patients with endometrial cancer. Materials and Methods This prospective study included consecutive adult patients with a suspected uterine tumor who underwent MRI and MR elastography between October 2022 and July 2023. A region of interest delineated on T2-weighted magnitude images was duplicated on MR elastography images and used to calculate c (stiffness in meters per second) and φ (viscosity in radians) values. Pathologic assessment of hysterectomy specimens for LVSI served as the reference standard. Data were compared between LVSI-positive and -negative groups with use of the Mann-Whitney U test. Multivariable logistic regression was used to determine variables associated with LVSI positivity and develop diagnostic models for predicting LVSI. Model performance was assessed with use of area under the receiver operating characteristic curve (AUC) and compared using the DeLong test. Results A total of 101 participants were included, 72 who were LVSI-negative (median age, 53 years [IQR, 48-62 years]) and 29 who were LVSI-positive (median age, 54 years [IQR, 49-60 years]). The tumor stiffness in the LVSI-positive group was higher than in the LVSI-negative group (median, 4.1 m/sec [IQR, 3.2-4.6 m/sec] vs 2.2 m/sec [IQR, 2.0-2.8 m/sec]; P < .001). Tumor volume, cancer antigen 125 level, and tumor stiffness were associated with LVSI positivity (adjusted odds ratio range, 1.01-9.06; P range, <.001-.04). The combined model (AUC, 0.93) showed better performance for predicting LVSI compared with clinical-radiologic model (AUC, 0.77; P = .003) and similar performance to the MR elastography-based model (AUC, 0.89; P = .06). Conclusion The addition of tumor stiffness as measured at MR elastography into a clinical-radiologic model improved prediction of LVSI in patients with endometrial cancer. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Ehman in this issue.

Cervical lymph node metastasis prediction from papillary thyroid carcinoma US videos: a prospective multicenter study.

BACKGROUND: Prediction of lymph node metastasis (LNM) is critical for individualized management of papillary thyroid carcinoma (PTC) patients to avoid unnecessary overtreatment as well as undesired under-treatment. Artificial intelligence (AI) trained by thyroid ultrasound (US) may improve prediction performance. METHODS: From September 2017 to December 2018, patients with suspicious PTC from the first medical center of the Chinese PLA general hospital were retrospectively enrolled to pre-train the multi-scale, multi-frame, and dual-direction deep learning (MMD-DL) model. From January 2019 to July 2021, PTC patients from four different centers were prospectively enrolled to fine-tune and independently validate MMD-DL. Its diagnostic performance and auxiliary effect on radiologists were analyzed in terms of receiver operating characteristic (ROC) curves, areas under the ROC curve (AUC), accuracy, sensitivity, and specificity. RESULTS: In total, 488 PTC patients were enrolled in the pre-training cohort, and 218 PTC patients were included for model fine-tuning (n = 109), internal test (n = 39), and external validation (n = 70). Diagnostic performances of MMD-DL achieved AUCs of 0.85 (95% CI: 0.73, 0.97) and 0.81 (95% CI: 0.73, 0.89) in the test and validation cohorts, respectively, and US radiologists significantly improved their average diagnostic accuracy (57% vs. 60%, P = 0.001) and sensitivity (62% vs. 65%, P < 0.001) by using the AI model for assistance. CONCLUSIONS: The AI model using US videos can provide accurate and reproducible prediction of cervical lymph node metastasis in papillary thyroid carcinoma patients preoperatively, and it can be used as an effective assisting tool to improve diagnostic performance of US radiologists. TRIAL REGISTRATION: We registered on the Chinese Clinical Trial Registry website with the number ChiCTR1900025592.

Different tracers for sentinel node detection in gynecologic oncology.

PURPOSE OF REVIEW: In the past decade, sentinel lymph node (SLN) mapping has progressively substituted full lymphadenectomies in gynecologic oncology. In this article, we review the most relevant and the latest literature on this topic. RECENT FINDINGS: In endometrial and cervical cancer, the current evidence further support the value of indocyanine green (ICG) as tracer of choice for SLN mapping. Experience in vulvar cancer is more limited, with ICG used together with technetium-99 m (Tc-99m) as a dual tracer but ICG, so far, has not been a game changer in this setting as it has been for cervical and endometrial cancer. SUMMARY: For most gynecologic cancers, ICG fluorescence imaging is considered now a days the tracer of choice for lymphatic mapping. However, in early-stage vulvar cancer, SLN biopsy with radioactive tracer continues to be the standard-of-care in lymph node status assessment.

MRI radiomics and biological correlations for predicting axillary lymph node burden in early-stage breast cancer.

BACKGROUND AND AIMS: Preoperative prediction of axillary lymph node (ALN) burden in patients with early-stage breast cancer is pivotal for individualised treatment. This study aimed to develop a MRI radiomics model for evaluating the ALN burden in early-stage breast cancer and to provide biological interpretability to predictions by integrating radiogenomic data. METHODS: This study retrospectively analyzed 1211 patients with early-stage breast cancer from four centers, supplemented by data from The Cancer Imaging Archive (TCIA) and Duke University (DUKE). MRI radiomic features were extracted from dynamic contrast-enhanced MRI images and an ALN burden-related radscore was constructed by the backpropagation neural network algorithm. Clinical and combined models were developed, integrating ALN-related clinical variables and radscore. The Kaplan-Meier curve and log-rank test were used to assess the prognostic differences between the predicted high- and low-ALN burden groups in both Center I and DUKE cohorts. Gene set enrichment and immune infiltration analyses based on transcriptomic TCIA and TCIA Breast Cancer dataset were used to investigate the biological significance of the ALN-related radscore. RESULTS: The MRI radiomics model demonstrated an area under the curve of 0.781-0.809 in three validation cohorts. The predicted high-risk population demonstrated a poorer prognosis (log-rank P < .05 in both cohorts). Radiogenomic analysis revealed migration pathway upregulation and cell differentiation pathway downregulation in the high radscore groups. Immune infiltration analysis confirmed the ability of radiological features to reflect the heterogeneity of the tumor microenvironment. CONCLUSIONS: The MRI radiomics model effectively predicted the ALN burden and prognosis of early-stage breast cancer. Moreover, radiogenomic analysis revealed key cellular and immune patterns associated with the radscore.

Lymph node imaging for thyroid cancer.

Cervical lymph nodes (LNs) in the central (level VI) and lateral (levels II-V) compartments of the neck are the most common sites of locoregional metastases associated with thyroid cancer. Prophylactic nodal dissections are uncommon in modern thyroid surgery and are not routinely performed due to concern for increased morbidity and do not offer improved survival. Therefore, a selective approach for LN dissections is increasingly important. Preoperatively, this is most frequently assessed with cervical ultrasound (US). Contrast-enhanced computed tomography (CT) of the neck can also be used for preoperative assessment. Both US and CT imaging can be used to characterise LNs in levels II-VI and their risk of malignancy based on size, morphology, and growth. US-guided fine-needle aspiration of equivocal LN with thyroglobulin (Tg) washout can also determine if a LN harbours malignancy. For postoperative surveillance after total thyroidectomy, both US and CT continue to play an important role at 6-12 months intervals. These patients may also benefit from additional biochemical data such as Tg levels in addition to LN and thyroid bed imaging. Thyroid uptake scans may also play a role in LN surveillance postoperatively for well-differentiated thyroid carcinoma in certain clinical contexts. Less commonly, positron emitted tomography may play a role, but is typically reserved for patients with aggressive or radioactive iodine refractory disease.

R2* mapping and reduced field-of-view diffusion-weighted imaging for preoperative assessment of nonenlarged lymph node metastasis in rectal cancer.

The aim of the current study is to investigate the diagnostic value of R2* mapping versus reduced field-of-view diffusion-weighted imaging (rDWI) of the primary lesion of rectal cancer for preoperative prediction of nonenlarged lymph node metastasis (NLNM). Eighty-one patients with pathologically confirmed rectal cancer underwent preoperative R2* mapping and rDWI sequences before total mesorectal excisions and accompanying regional lymph node dissections. Two radiologists independently performed whole-tumor measurements of R2* and apparent diffusion coefficient (ADC) parameters on primary lesions of rectal cancer. Patients were divided into positive (NLNM+) and negative (NLNM-) groups based on their pathological analysis. The tumor location, maximum diameter of the tumor, and maximum short diameter of the lymph node were assessed. R2* and ADC, pT stage, tumor grade, status of mesorectal fascia, and extramural vascular invasion were also studied for their potential relationships with NLNM using multivariate logistic regression analysis. The NLNM+ group had significantly higher R2* (43.56 ± 8.43 vs. 33.87 ± 9.57, p < 0.001) and lower ADC (1.00 ± 0.13 vs. 1.06 ± 0.22, p = 0.036) than the NLNM- group. R2* and ADC were correlated to lymph node metastasis (r = 0.510, p < 0.001 for R2*; r = -0.235, p = 0.035 for ADC). R2* and ADC showed good and moderate diagnostic abilities in the assessment of NLNM status with corresponding area-under-the-curve values of 0.795 and 0.636. R2* provided a significantly better diagnostic performance compared with ADC for the prediction of NLNM status (z = 1.962, p = 0.0498). The multivariate logistic regression analysis demonstrated that R2* was a compelling factor of lymph node metastasis (odds ratio = 56.485, 95% confidence interval: 5.759-554.013; p = 0.001). R2* mapping had significantly higher diagnostic performance than rDWI from the primary tumor of rectal cancer in the prediction of NLNM status.

Disease extent according to baseline [18F]fluorodeoxyglucose PET/CT and molecular subtype: prediction of axillary treatment response after neoadjuvant systemic therapy for breast cancer.

BACKGROUND: Axillary disease extent according to baseline [18F]fluorodeoxyglucose PET/CT combined with pathological axillary treatment response has been proposed to guide de-escalation of axillary treatment for clinically node-positive breast cancer patients treated with neoadjuvant systemic therapy. The aim of this study was to assess whether axillary disease extent according to baseline [18F]fluorodeoxyglucose PET/CT and breast cancer molecular subtype are predictors of axillary pCR. METHODS: This study included clinically node-positive patients treated with neoadjuvant systemic therapy in the prospective Radioactive Iodine Seed placement in the Axilla with Sentinel lymph node biopsy ('RISAS') trial (NCT02800317) with baseline [18F]fluorodeoxyglucose PET/CT imaging available. The predictive value of axillary disease extent according to baseline [18F]fluorodeoxyglucose PET/CT and breast cancer molecular subtype to estimate axillary pCR was evaluated using logistic regression analysis. Discriminative ability is expressed using ORs with 95% confidence intervals. RESULTS: Overall, 185 patients were included, with an axillary pCR rate of 29.7%. The axillary pCR rate for patients with limited versus advanced baseline axillary disease according to [18F]fluorodeoxyglucose PET/CT was 31.9% versus 26.1% respectively. Axillary disease extent was not a significant predictor of axillary pCR (OR 0.75 (95% c.i. 0.38 to 1.46) (P = 0.404)). There were significant differences in axillary pCR rates between breast cancer molecular subtypes. The lowest probability (7%) was found for hormone receptor+/human epidermal growth factor receptor 2- tumours. Using this category as a reference group, significantly increased ORs of 14.82 for hormone receptor+/human epidermal growth factor receptor 2+ tumours, 40 for hormone receptor-/human epidermal growth factor receptor 2+ tumours, and 6.91 for triple-negative tumours were found (P < 0.001). CONCLUSION: Molecular subtype is a significant predictor of axillary pCR after neoadjuvant systemic therapy, whereas axillary disease extent according to baseline [18F]fluorodeoxyglucose PET/CT is not.

Distinct impacts of radiological appearance on lymph node metastasis and prognosis based on solid size in clinical T1 non-small cell lung cancer.

BACKGROUND: Solid nodules (SN) had more aggressive features and a poorer prognosis than part-solid nodules (PSN). This study aimed to evaluate the specific impacts of nodule radiological appearance (SN vs. PSN) on lymph node metastasis and prognosis based on solid size in cT1 non-small cell lung cancer (NSCLC). METHODS: Patients with cT1 NSCLC who underwent anatomical resection between 2010 and 2019 were retrospectively screened. Univariable and multivariable logistic regression analyses were adopted to evaluate the associations between nodule radiological appearance and lymph node metastasis. The log-rank test and Cox regression analyses were applied for prognostic evaluation. The cumulative recurrence risk was evaluated by the competing risk model. RESULTS: There were 958 and 665 NSCLC patients with PSN and SN. Compared to the PSN group, the SN arm had a higher overall lymph node metastasis rate (21.7% vs. 2.7%, P < 0.001), including nodal metastasis at N1 stations (17.7% vs. 2.1%), N2 stations (14.0% vs. 1.6%), and skip nodal metastasis (3.9% vs. 0.6%). However, for cT1a NSCLC, no significant difference existed between SN and PSN (0 vs. 0.4%, P = 1). In addition, the impacts of nodule radiological appearance on lymph node metastasis varied between nodal stations. Solid NSCLC had an inferior prognosis than part-solid patients (5-year disease-free survival: 79.3% vs. 96.2%, P < 0.001). The survival inferiority only existed for cT1b and cT1c NSCLC, but not for cT1a. Strikingly, even for patients with nodal involvement, SN still had a poorer disease-free survival (P = 0.048) and a higher cumulative incidence of recurrence (P < 0.001) than PSN. Specifically, SN had a higher recurrence risk than PSN at each site. Nevertheless, the distribution of recurrences between SN and PSN was similar, except that N2 lymph node recurrences were more frequent in solid NSCLC (28.21% vs. 7.69%, P = 0.041). CONCLUSION: SN had higher risks of lymph node metastasis and poorer prognosis than PSN for cT1b and cT1c NSCLC, but not for cT1a. SN exhibited a greater proportion of N2 lymph node recurrence than PSN. SN and PSN needed distinct strategies for nodal evaluation and postoperative follow-up.

Incidence rate of occult lymph node metastasis in clinical T1-2N0M0 small cell lung cancer patients and radiomic prediction based on contrast-enhanced CT imaging: a multicenter study : Original research.

BACKGROUND: This study aimed to explore the incidence of occult lymph node metastasis (OLM) in clinical T1 - 2N0M0 (cT1 - 2N0M0) small cell lung cancer (SCLC) patients and develop machine learning prediction models using preoperative intratumoral and peritumoral contrast-enhanced CT-based radiomic data. METHODS: By conducting a retrospective analysis involving 242 eligible patients from 4 centeres, we determined the incidence of OLM in cT1 - 2N0M0 SCLC patients. For each lesion, two ROIs were defined using the gross tumour volume (GTV) and peritumoral volume 15 mm around the tumour (PTV). By extracting a comprehensive set of 1595 enhanced CT-based radiomic features individually from the GTV and PTV, five models were constucted and we rigorously evaluated the model performance using various metrics, including the area under the curve (AUC), accuracy, sensitivity, specificity, calibration curve, and decision curve analysis (DCA). For enhanced clinical applicability, we formulated a nomogram that integrates clinical parameters and the rad_score (GTV and PTV). RESULTS: The initial investigation revealed a 33.9% OLM positivity rate in cT1 - 2N0M0 SCLC patients. Our combined model, which incorporates three radiomic features from the GTV and PTV, along with two clinical parameters (smoking status and shape), exhibited robust predictive capabilities. With a peak AUC value of 0.772 in the external validation cohort, the model outperformed the alternative models. The nomogram significantly enhanced diagnostic precision for radiologists and added substantial value to the clinical decision-making process for cT1 - 2N0M0 SCLC patients. CONCLUSIONS: The incidence of OLM in SCLC patients surpassed that in non-small cell lung cancer patients. The combined model demonstrated a notable generalization effect, effectively distinguishing between positive and negative OLMs in a noninvasive manner, thereby guiding individualized clinical decisions for patients with cT1 - 2N0M0 SCLC.

Sentinel lymph node detection in thyroid carcinoma using [68Ga]Ga-tilmanocept PET/CT: a proof-of-concept study.

PURPOSE: Sentinel lymph node (SLN) biopsy is rarely used for thyroid carcinoma staging. This is due to challenges associated with conventional Tc-99m-labeled tracers, often producing a large hotspot at the injection site, potentially hiding nearby SLNs (shine-through effect). The aim of this study was to demonstrate the feasibility and effectiveness of SLN visualization using the new PET tracer [68Ga]Ga-tilmanocept. METHODS: Patients with thyroid carcinoma underwent ultrasound-guided peritumoral injection of [68Ga]Ga-tilmanocept and ICG-[99mTc]Tc-nanocolloid. [68Ga]Ga-tilmanocept PET/CT scans were conducted at 15 min and 60 min post-injection to visualize the SLNs. SLN biopsy was performed using ICG-[99mTc]TC-nanocolloid for intraoperative identification. The corresponding lymph node level was resected for reference. RESULTS: Seven differentiated thyroid carcinoma (DTC) and 3 medullary thyroid carcinoma (MTC) patients were included, of which 6 were clinically node-negative. The median number of SLNs detected on [68Ga]Ga-tilmanocept PET/CT and resected was 3 (range 1-4) and 3 (range 1-5), respectively. Eight SLNs were found on PET/CT in the central compartment and 19 in the lateral compartment. The SLN procedure detected (micro)metastases in all patients except one. Seventeen of 27 pathologically assessed SLNs were positive, 8 negative, and 2 did not contain lymph node tissue, which led to upstaging in 5 out of 6 clinically node-negative patients. CONCLUSIONS: [68Ga]Ga-tilmanocept PET/CT identified SLNs in all patients, mainly in the lateral neck. The SLNs were successfully surgically detected and resected using ICG-[99mTc]Tc-nanocolloid. This technique has the potential to improve neck staging, enabling more personalized treatment of thyroid cancer according to the lymph node status. TRIAL REGISTRATION: 2021-002470-42 (EudraCT).

Comparison of the diagnostic value of [68 Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT in patients with T stage ≤ 2a2 uterine cervical cancer: a prospective study.

PURPOSE: To compare the diagnostic value of [68 Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT in patients with T stage ≤ 2a2 uterine cervical cancer patients. METHODS: Patients pathologically diagnosed with cervical cancer and with a T stage ≤ T2a2 were prospectively enrolled. All patients underwent whole-body [68 Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT within 2 weeks, and surgical treatment was performed within 10 days after PET. RESULTS: Twenty-five patients were enrolled. Twenty patients underwent radical hysterectomy, among which all of them underwent pelvic lymphadenectomy, and 10 patients underwent para-aortic lymphadenectomy. Three patients received merely laparoscopic lymphadenectomy without hysterectomy. Two patients with both [18F]FDG and [68 Ga]Ga-FAPI-04 lymph node high metabolism were staged as FIGO IIIC1r, and concurrent chemoradiation therapy (CCRT) was performed. [18F]FDG and [68 Ga]Ga-FAPI-04 had equivalent detection ability on primary tumors, with a positive detection rate of 96.0%. The accuracy of T staging using [18F]FDG and [68 Ga]Ga-FAPI-04 was relatively 50% and 55.0%. Elevated and underrated staging was due to misdiagnosis of either vaginal infiltration or tumor size. In terms of lymph node metastasis detection, the specificity of [68 Ga]Ga-FAPI-04 was 100% (95% CI, 84.6% ~ 100.0%), which was significantly higher than [18F]FDG (59.1% (95% CI, 36.4% ~ 79.3%)) (p = 0.004). CONCLUSION: [68 Ga]Ga-FAPI-04 PET/MR and [18F]FDG PET/CT demonstrated an equivalent detection ability on cervical cancer primary tumors. However, [68 Ga]Ga-FAPI-04 PET/MR's diagnostic value in lymph node metastasis was significantly higher than [18F]FDG PET/CT. [68 Ga]Ga-FAPI-04 PET/MR has the potential for more accurate treatment planning, thus clarifying fertility preservation indications for early-stage young patients.

[68Ga]Ga-FAPI-46 PET/CT for penile cancer - a feasibility study.

PURPOSE: Penile cancer is a rare entity and has a good prognosis in localized stage. Delayed surgical treatment of lymphatic disease is associated with poor overall survival but conventional imaging cannot detect occult lymph node metastasis sufficiently. Imaging cancer related fibroblasts has shown promising results as non-invasive staging tool in various tumor entities but has not yet been evaluated in penile cancer. METHODS: In this single-center pilot study, patients planned for surgical treatment for penile cancer underwent preoperatively [68Ga]Ga-FAPI-46 PET/CT. Post-operative histopathology was compared to [68Ga]Ga-FAPI-46 PET/CT results. RESULTS: From January 2022 to June 2022, a total number 11 patients with histopathologically proven penile cancer underwent surgery and received [68Ga]Ga-FAPI-46 PET/CT prior therapy. 8 primary tumor sites and 4 lymph node regions were analyzed. FAPI uptake was increased on primary tumor site (SUVmax 16.2 (9.1 - 25.8)). Histopathological proven lymph node regions showed highly increased FAPI uptakes (SUVmax 17.9 (16.4 - 23.5) on [68Ga]Ga-FAPI-46 PET/CT. CONCLUSION: In this first pilot cohort, there were no false-positive FAPI uptake which might allow the detection of occult lymph node metastasis by [68Ga]Ga-FAPI-46 PET/CT and might consequently lead to omitting lymph node regions during surgery that had no increased FAPI uptake pre-operatively.

First-in-human validation of a DROP-IN ß-probe for robotic radioguided surgery: defining optimal signal-to-background discrimination algorithm.

PURPOSE: In radioguided surgery (RGS), radiopharmaceuticals are used to generate preoperative roadmaps (e.g., PET/CT) and to facilitate intraoperative tracing of tracer avid lesions. Within RGS, there is a push toward the use of receptor-targeted radiopharmaceuticals, a trend that also has to align with the surgical move toward minimal invasive robotic surgery. Building on our initial ex vivo evaluation, this study investigates the clinical translation of a DROP-IN ß probe in robotic PSMA-guided prostate cancer surgery. METHODS: A clinical-grade DROP-IN ß probe was developed to support the detection of PET radioisotopes (e.g., 68 Ga). The prototype was evaluated in 7 primary prostate cancer patients, having at least 1 lymph node metastases visible on PSMA-PET. Patients were scheduled for radical prostatectomy combined with extended pelvic lymph node dissection. At the beginning of surgery, patients were injected with 1.1 MBq/kg of [68Ga]Ga-PSMA. The ß probe was used to trace PSMA-expressing lymph nodes in vivo. To support intraoperative decision-making, a statistical software algorithm was defined and optimized on this dataset to help the surgeon discriminate between probe signals coming from tumors and healthy tissue. RESULTS: The DROP-IN ß probe helped provide the surgeon with autonomous and highly maneuverable tracer detection. A total of 66 samples (i.e., lymph node specimens) were analyzed in vivo, of which 31 (47%) were found to be malignant. After optimization of the signal cutoff algorithm, we found a probe detection rate of 78% of the PSMA-PET-positive samples, a sensitivity of 76%, and a specificity of 93%, as compared to pathologic evaluation. CONCLUSION: This study shows the first-in-human use of a DROP-IN ß probe, supporting the integration of ß radio guidance and robotic surgery. The achieved competitive sensitivity and specificity help open the world of robotic RGS to a whole new range of radiopharmaceuticals.

[68 Ga]Ga-FAPI-46 PET/CT for locoregional lymph node staging in urothelial carcinoma of the bladder prior to cystectomy: initial experiences from a pilot analysis.

INTRODUCTION: [68 Ga]Ga-FAPI-46 PET/CT is a novel hybrid imaging method that previously showed additional diagnostic value in the assessment of distant urothelial carcinoma lesions. We hypothesized that patients with bladder cancer benefit from [68 Ga]Ga-FAPI-46 PET/CT prior to radical cystectomy for locoregional lymph node staging. MATERIALS AND METHODS: Eighteen patients underwent [68 Ga]Ga-FAPI-46 PET/CT for evaluation of lymph node (LN) status in predefined LN regions. Two hundred twenty-nine intraoperatively removed LN served as histopathological reference standard. RESULTS: Urothelial carcinoma (UC) spread was found in ten LN in seven different regions (14.3%). Hereby, [68 Ga]Ga-FAPI-46 PET/CT was positive in four out of seven regions (57.1%) and showed significantly increased FAPI uptake compared to non-pathological regions. In the remaining three out of seven (42.9%) regions, [68 Ga]Ga-FAPI-46 PET/CT was rated negative since no pathological increased FAPI uptake was detected or the proximity of the urinary tract prevented a differentiation from physiological uptake. CT was inconspicuous in these three regions. In total, two FAP-positive LN regions were found without histopathological counterpart. Overall, sensitivity, specificity, positive predictive value, and negative predictive value were 57.1%, 95.2%, 66.7%, and 93.0% for PET imaging. CONCLUSION: In summary, this innovative [68 Ga]Ga-FAPI-46 PET/CT method showed high specificity and negative predictive value in patients with bladder UC with a future potential to optimize therapy planning.

2-[18F]FDG PET-based quantification of lymph node metabolic heterogeneity for predicting lymph node metastasis in patients with colorectal cancer.

BACKGROUND AND PURPOSE: The pre-surgical estimation of lymph node (LN) metastasis in colorectal cancer (CRC) poses a significant diagnostic predicament. The associations between LN morphology, density, and metabolic heterogeneity and LN metastasis status in CRCs have been seldomly examined through the lens of radiomics. This research aimed to assess 2-[18F]FDG PET-based quantification of intratumoral metabolic heterogeneity for predicting lymph node metastasis in patients with colorectal cancer. MATERIALS AND METHODS: The construction of the model utilized data from 264 CRC patients, all of whom underwent preoperative 2-[18F]FDG PET/CT. Radiomic features were extracted from PET and CT images of LNs. Least absolute shrinkage and selection operator (LASSO) regression was implemented for selecting pertinent imaging features with a tenfold cross-validation. The predictive accuracy for LN metastasis status was juxtaposed against traditional methodologies (comprising CT-reported LN status and PET/CT-reported LN status) by deploying the receiver operating characteristic (ROC) curve analysis. The radiomics signature was evaluated based on discrimination, calibration, and clinical utility parameters. The model was further subjected to validation using an independent cohort of 132 patients from the period of January 2012 to June 2020. RESULTS: The radiomics model was composed of eight significant radiomic features (five from PET and three from CT), encapsulating metabolic and density heterogeneity. The radiomics signature (area under the curve (AUC), 0.908) showcased a significantly superior performance compared to CT-reported LN status (AUC, 0.563, P < 0.001) and PET/CT-reported LN status (AUC, 0.64, P < 0.001) for predicting LN-positive or LN-negative status. The radiomics signature (AUC, 0.885) also showcased a significantly superior performance compared to CT-reported LN status (AUC, 0.587, P < 0.001) and PET/CT-reported LN status (AUC, 0.621, P < 0.001) to identify N1 and N2. This signature maintained its independence from clinical risk factors and exhibited robustness in the validation test set. Decision curve analysis attested to the clinical utility of the radiomics signature. CONCLUSIONS: The radiomics signature based on 2-[18F]FDG PET/CT, which derived image features directly from LNs irrespective of clinical risk factors, displayed enhanced diagnostic performance compared to conventional CT or PET/CT-reported LN status. This allows for the identification of pre-surgical LN metastasis status and facilitates a patient-specific prediction of LN metastasis status in CRC patients.

Defining the optimal target-to-background ratio to identify positive lymph nodes in prostate cancer patients undergoing robot-assisted [99mTc]Tc-PSMA radioguided surgery: updated results and ad interim analyses of a prospective phase II study.

INTRODUCTION: Prostate-specific membrane antigen radioguided surgery (PSMA-RGS) might identify lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing extended pelvic lymph node dissection (ePLND). The optimal target-to-background (TtB) ratio to define RGS positivity is still unknown. MATERIALS & METHODS: Ad interim analyses which focused on 30 patients with available pathological information were conducted. All patients underwent preoperative PSMA positron emission tomography (PET). 99m-Technetium-PSMA imaging and surgery ([99mTc]Tc-PSMA-I&S) was administered the day before surgery. In vivo measurements were conducted using an intraoperative gamma probe. Performance characteristics and implications associated with different TtB ratios were assessed. RESULTS: Overall, 9 (30%) patients had LNI, with 22 (13%) and 80 (11%) positive regions and lymph nodes, respectively. PSMA-RGS showed uptakes in 12 (40%) vs. 7 (23%) vs. 6 (20%) patients for a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4. At a per-region level, sensitivity, specificity and accuracy for a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4 were 72%, 88% and 87% vs. 54%, 98% and 92% vs. 36%, 99% and 91%. Performing ePLND only in patients with suspicious spots at PSMA PET (n = 7) would have spared 77% ePLNDs at the cost of missing 13% (n = 3) pN1 patients. A TtB ratio ≥ 2 at RGS identified 8 (24%) suspicious areas not detected by PSMA PET, of these 5 (63%) harbored LNI, with one pN1 patient (11%) that would have been missed by PSMA PET. Adoption of a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4, would have allowed to spare 18 (60%) vs. 23 (77%) vs. 24 (80%) ePLNDs missing 2 (11%) vs. 3 (13%) vs. 4 (17%) pN1 patients. CONCLUSIONS: PSMA-RGS using a TtB ratio ≥ 2 to identify suspicious nodes, could allow to spare > 50% ePLNDs and would identify additional pN1 patients compared to PSMA PET and higher TtB ratios.

Preoperative evaluation of mediastinal lymph nodes in non-small cell lung cancer using [68Ga]FAPI-46 PET/CT: a prospective pilot study.

PURPOSE: Mediastinal nodal staging is crucial for surgical candidate selection in non-small cell lung cancer (NSCLC), but conventional imaging has limitations often necessitating invasive staging. We investigated the additive clinical value of fibroblast activation protein inhibitor (FAPI) PET/CT, an imaging technique targeting fibroblast activation protein, for mediastinal nodal staging of NSCLC. METHODS: In this prospective pilot study, we enrolled patients scheduled for surgical resection of NSCLC based on specific criteria designed to align with indications for invasive staging procedures. Patients were included when meeting at least one of the following: (1) presence of FDG-positive N2 lymph nodes, (2) clinical N1 stage, (3) central tumor location or tumor diameter of ≥ 3 cm, and (4) adenocarcinoma exhibiting high FDG uptake. [68Ga]FAPI-46 PET/CT was performed before surgery after a staging workup including [18F]FDG PET/CT. The diagnostic accuracy of [68Ga]FAPI-46 PET/CT for "N2" nodes was assessed through per-patient visual assessment and per-station quantitative analysis using histopathologic results as reference standards. RESULTS: Twenty-three patients with 75 nodal stations were analyzed. Histopathologic examination confirmed that nine patients (39.1%) were N2-positive. In per-patient assessment, [68Ga]FAPI-46 PET/CT successfully identified metastasis in eight patients (sensitivity 0.89 (0.52-1.00)), upstaging three patients compared to [18F]FDG PET/CT. [18F]FDG PET/CT detected FDG-avid nodes in six (42.8%) of 14 N2-negative patients. Among them, five were considered non-metastatic based on calcification and distribution pattern, and one was considered metastatic. In contrast, [68Ga]FAPI-46 PET/CT correctly identified all non-metastatic patients solely based on tracer avidity. In per-station analysis, [68Ga]FAPI-46 PET/CT discriminated metastasis more effectively compared to [18F]FDG PET/CT-based (AUC of ROC curve 0.96 (0.88-0.99) vs. 0.68 (0.56-0.78), P < 0.001). CONCLUSION: [68Ga]FAPI-46 PET/CT holds promise as an imaging tool for preoperative mediastinal nodal staging in NSCLC, with improved sensitivity and the potential to reduce false-positive results, optimizing the need for invasive staging procedures.

Preoperative assessment of lymph nodal metastases with [68Ga]Ga-DOTATOC PET radiomics for improved surgical planning in well-differentiated pancreatic neuroendocrine tumours.

PURPOSE: 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. METHODS: 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). RESULTS: LN metastases were detected in 29/72 patients at histology. [68Ga]Ga-DOTATOC PET qualitative examination of LN involvement provided bACC = 60%, SN = 24%, SP = 95%, PPV = 78% and NPV = 65%. The best-performing radiomic model provided a bACC = 70%, SN = 77%, SP = 61%, PPV = 60% and NPV = 83% (outperforming the control model, p < 0.05*). CONCLUSION: In this study, [68Ga]Ga-DOTATOC PET radiomics allowed to increase diagnostic sensitivity in detecting LN metastases from 24 to 77% in NF-PanNET patients candidate to surgery. Especially in case of micrometastatic involvement, this approach might assist clinicians in a better patients' stratification.

Investigation of correlation between shear wave elastography and lymphangiogenesis in invasive breast cancer and diagnosis of axillary lymph node metastasis.

BACKGROUND: Accurate evaluation of axillary lymph node metastasis (LNM) in breast cancer is very important. A large number of hyperplastic and dilated lymphangiogenesis cases can usually be found in the pericancerous tissue of breast cancer to promote the occurrence of tumor metastasis.Shear wave elastography (SWE) can be used as an important means for evaluating pericancerous stiffness. We determined the stiffness of the pericancerous by SWE to diagnose LNM and lymphangiogenesis in invasive breast cancer (IBC). METHODS: Patients with clinical T1-T2 stage IBC who received surgical treatment in our hospital from June 2020 to December 2020 were retrospectively enrolled. A total of 299 patients were eventually included in the preliminary study, which included an investigation of clinicopathological features, ultrasonic characteristics, and SWE parameters. Multivariable logistic regression analysis was used to establish diagnostic model and evaluated its diagnostic performance of LNM. The correlation among SWE values, collagen volume fraction (CVF), and microlymphatic density (MLD) in primary breast cancer lesions was analyzed in another 97 patients. RESULTS: The logistic regression model is Logit(P)=-1.878 + 0.992*LVI-2.010*posterior feature enhancement + 1.230*posterior feature shadowing + 0.102*posterior feature combined pattern + 0.009*Emax. The optimum cutoff value of the logistic regression model was 0.365, and the AUC (95% CI) was 0.697 (0.636-0.758); the sensitivity (70.7 vs. 54.3), positive predictive value (PPV) (54.0 vs. 50.8), negative predictive value (NPV) (76.9 vs. 69.7), and accuracy (65.2 vs. 61.9) were all higher than Emax. There was no correlation between the SWE parameters and MLD in primary breast cancer lesions. CONCLUSIONS: The logistic regression model can help us to determine LNM, thus providing more imaging basis for the selection of preoperative treatment. The SWE parameter of the primary breast cancer lesion cannot reflect the peritumoral lymphangiogenesis, and we still need to find a new ultrasonic imaging method.

An integrated model incorporating deep learning, hand-crafted radiomics and clinical and US features to diagnose central lymph node metastasis in patients with papillary thyroid cancer.

OBJECTIVE: To evaluate the value of an integrated model incorporating deep learning (DL), hand-crafted radiomics and clinical and US imaging features for diagnosing central lymph node metastasis (CLNM) in patients with papillary thyroid cancer (PTC). METHODS: This retrospective study reviewed 613 patients with clinicopathologically confirmed PTC from two institutions. The DL model and hand-crafted radiomics model were developed using primary lesion images and then integrated with clinical and US features selected by multivariate analysis to generate an integrated model. The performance was compared with junior and senior radiologists on the independent test set. SHapley Additive exPlanations (SHAP) plot and Gradient-weighted Class Activation Mapping (Grad-CAM) were used for the visualized explanation of the model. RESULTS: The integrated model yielded the best performance with an AUC of 0.841. surpassing that of the hand-crafted radiomics model (0.706, p < 0.001) and the DL model (0.819, p = 0.26). Compared to junior and senior radiologists, the integrated model reduced the missed CLNM rate from 57.89% and 44.74-27.63%, and decreased the rate of unnecessary central lymph node dissection (CLND) from 29.87% and 27.27-18.18%, respectively. SHAP analysis revealed that the DL features played a primary role in the diagnosis of CLNM, while clinical and US features (such as extrathyroidal extension, tumour size, age, gender, and multifocality) provided additional support. Grad-CAM indicated that the model exhibited a stronger focus on thyroid capsule in patients with CLNM. CONCLUSION: Integrated model can effectively decrease the incidence of missed CLNM and unnecessary CLND. The application of the integrated model can help improve the acceptance of AI-assisted US diagnosis among radiologists.