[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.

Application and subgroup analysis of competing risks model based on different lymph node staging systems in differentiated thyroid cancer.

Differentiated thyroid cancer (DTC) is the most common endocrine malignancy, with a rising incidence worldwide. Accurate prognostic models are essential for effective patient management. This study evaluates the prognostic value of various lymph node staging systems in DTC using a competing risks model. We used SEER database records (1998-2016) of 16,527 DTC patients, analyzing N stage, positive lymph node numbers (PLNNs), metastatic lymph node ratio (MLNR), log odds of positive lymph nodes (LODDS), and log odds of the negative lymph node (NLN)/T stage ratio (LONT). Univariate and multivariate analyses in a competing risks model were performed, along with subgroup analyses based on demographic and clinical characteristics. In this study of 16,527 patients with DTC, different lymph node staging systems showed different prognostic correlations in univariate and multivariate analyses. In particular, PLNNs showed significant prognostic correlations in several subgroups. Additionally, PLNNs were more suitable as a lymph node staging system for DTC than LODDS and MLNR in N1 stage subgroups, with an optimal cut-off of 13. Receiver operating characteristic curves, calibration curves and nomograms improved the clinical utility of the prognostic model based on PLNNs. Using competing risks model and subgroup analyses, we found that PLNNs had the best prognostic discriminatory efficacy for patients with DTC, especially those with N1 stage disease, and had an optimal cut-off value of 13.

Diagnostic potential of [18F]FDG PET/MRI in non-small cell lung cancer lymph node metastasis: a meta-analysis.

PURPOSE: This meta-analysis evaluated the diagnostic accuracy and diagnostic value of [18F]FDG PET/MRI for mediastinal lymph node staging of NSCLC. METHODS: Relevant articles in PubMed, Embase, Web of Science, and the Cochrane Library were searched until January 2023. Research evaluating [18F]FDG PET/MRI for mediastinal lymph node staging of NSCLC was included. Pooled estimates of sensitivity, specificity, PLR, and NLR were calculated by the "Stata" software. RESULTS: Nine researches were included, containing 618 patients. The pooled sensitivity of [18F]FDG PET/MRI for detecting mediastinal lymph node staging of NSCLC was 0.82 (0.70-0.90), and the pooled specificity was 0.88 (0.82-0.93). PLR and NLR were 7.38 (4.73-11.52) and 0.20 (0.11-0.36), respectively. The AUC value of this imaging modality was 0.92 (0.90-0.94). The post-test probability for [18F]FDG PET/MRI might rise to 88% when the pre-test probability was set at 50%. CONCLUSIONS: We considered [18F]FDG PET/MRI as an effective imaging tool with relatively high specificity and sensitivity. It has great potential to be used in the clinical management of patients in NSCLC who are amenable to early surgery. More studies with large sample sizes in the same direction are needed in future to obtain more reliable evidence-based support.

Noninvasive Staging of Lymph Node Status in Breast Cancer Using Machine Learning: External Validation and Further Model Development.

BACKGROUND: Most patients diagnosed with breast cancer present with a node-negative disease. Sentinel lymph node biopsy (SLNB) is routinely used for axillary staging, leaving patients with healthy axillary lymph nodes without therapeutic effects but at risk of morbidities from the intervention. Numerous studies have developed nodal status prediction models for noninvasive axillary staging using postoperative data or imaging features that are not part of the diagnostic workup. Lymphovascular invasion (LVI) is a top-ranked predictor of nodal metastasis; however, its preoperative assessment is challenging. OBJECTIVE: This paper aimed to externally validate a multilayer perceptron (MLP) model for noninvasive lymph node staging (NILS) in a large population-based cohort (n=18,633) and develop a new MLP in the same cohort. Data were extracted from the Swedish National Quality Register for Breast Cancer (NKBC, 2014-2017), comprising only routinely and preoperatively available documented clinicopathological variables. A secondary aim was to develop and validate an LVI MLP for imputation of missing LVI status to increase the preoperative feasibility of the original NILS model. METHODS: Three nonoverlapping cohorts were used for model development and validation. A total of 4 MLPs for nodal status and 1 LVI MLP were developed using 11 to 12 routinely available predictors. Three nodal status models were used to account for the different availabilities of LVI status in the cohorts and external validation in NKBC. The fourth nodal status model was developed for 80% (14,906/18,663) of NKBC cases and validated in the remaining 20% (3727/18,663). Three alternatives for imputation of LVI status were compared. The discriminatory capacity was evaluated using the validation area under the receiver operating characteristics curve (AUC) in 3 of the nodal status models. The clinical feasibility of the models was evaluated using calibration and decision curve analyses. RESULTS: External validation of the original NILS model was performed in NKBC (AUC 0.699, 95% CI 0.690-0.708) with good calibration and the potential of sparing 16% of patients with node-negative disease from SLNB. The LVI model was externally validated (AUC 0.747, 95% CI 0.694-0.799) with good calibration but did not improve the discriminatory performance of the nodal status models. A new nodal status model was developed in NKBC without information on LVI (AUC 0.709, 95% CI: 0.688-0.729), with excellent calibration in the holdout internal validation cohort, resulting in the potential omission of 24% of patients from unnecessary SLNBs. CONCLUSIONS: The NILS model was externally validated in NKBC, where the imputation of LVI status did not improve the model's discriminatory performance. A new nodal status model demonstrated the feasibility of using register data comprising only the variables available in the preoperative setting for NILS using machine learning. Future steps include ongoing preoperative validation of the NILS model and extending the model with, for example, mammography images.

Oncologic Staging with 68Ga-FAPI PET/CT Demonstrates a Lower Rate of Nonspecific Lymph Node Findings Than 18F-FDG PET/CT.

Nonspecific lymph node uptake on 18F-FDG PET/CT imaging is a significant pitfall for tumor staging. Fibroblast activation protein α expression on cancer-associated fibroblasts and some tumor cells is less sensitive to acute inflammatory stimuli, and fibroblast activation protein-directed PET may overcome this limitation. Methods: Eighteen patients from our prospective observational study underwent 18F-FDG and 68Ga fibroblast activation protein inhibitor (FAPI) PET/CT scans within a median of 2 d (range, 0-22 d). Lymph nodes were assessed on histopathology and compared with SUV measurements. Results: On a per-patient basis, lymph nodes were rated malignant in 10 (56%) versus 7 (39%) patients by 18F-FDG PET/CT versus 68Ga-FAPI PET/CT scans, respectively, with a respective accuracy of 55% versus 94% for true lymph node metastases. Five of 6 (83%) false-positive nodes on the 18F-FDG PET/CT scans were rated true negative by the 68Ga-FAPI PET/CT scans. On a per-lesion basis, tumor detection rates were similar (85/89 lesions, 96%). Conclusion: 68Ga-FAPI PET/CT imaging demonstrated higher accuracy for true nodal involvement and therefore has the potential to replace 18F-FDG PET/CT imaging for cancer staging.

Modified staging system of positive lymph nodes based nomogram in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) presents the similar trend and prevalence of lymph node metastasis to other biliary tract cancer. There is still a necessity and possibility for the current classification of lymph node in the 8th TNM of iCCA, which is the same as the criteria of hepatoma carcinoma (HCC), to further improve the prognostic capacity. We aim to explore the optimal positive lymph nodes cutoff value that could predict the survival outcomes of patients with iCCA and further establish a prognostic nomogram. METHOD: Clinical characteristics were retrospectively collected in 292 patients with iCCA from Sun Yat-sen University Cancer Center (SYSUCC) for preliminary analysis. A retrospective analysis of 107 patients with iCCA in the First Hospital of Dalian Medical University (FHDMU) was performed for verification. R software was used to determine the optimal cutoff value of positive lymph nodes (PLN) and further establish the nomogram with the Cox regression model in the primary cohort. RESULTS: In those patients who were graded into the N1 stage in 8th TNM staging system, the patients with PLN between 1 and 3 showed significantly better overall survival than those patients with more than 4 PLN (P < 0.0001). Moreover, there was a significant correlation between the new PLN classification and adverse clinical characteristic including Micro Invasion (P = 0.001), Lymph Vessel Invasion (P = 0.040), Satellite Sites (P < 0.001), and Tumor Size (P = 0.005). The PLN and ELN were both independent prognostic factors for survival outcomes in the multivariate analysis, and further showed large contribution to the nomogram. The nomogram achieved a satisfied C-index of 0.813 for overall survival (OS), 0.869 for progression-free survival (PFS) in the primary cohort, and 0.787 for OS, 0.762 for PFS in the validation cohort. CONCLUSION: The modified classification of PLN in iCCA could accurately stratify the N1 stage patients in 8th TNM staging system into two groups with significantly different overall survival. The development of this nomogram can offer new evidence to precisely post-operative management of iCCA patients.

Histology of the Primary Tumor Correlates with False Positivity of Integrated 18F-FDG-PET/CT Lymph Node Staging in Resectable Lung Cancer Patients.

This study aimed to evaluate the diagnostic accuracy and false positivity rate of lymph node (LN) staging assessed by integrated 18F-fluorodeoxyglucose positron emission computed tomography (18F-FDG-PET/CT) in patients with operable lung cancer to the tumor histology. In total, 129 consecutive patients with non-small-cell lung cancer (NSCLC) undergoing anatomical lung resections were included. Preoperative LN staging was evaluated in the relationship to the histology of the resected specimens (group 1: lung adenocarcinoma/LUAD; group 2: squamous cell carcinoma/SQCA). Statistical analysis was performed by the Mann-Whitney U-test, the chi2 test, and binary logistic regression analysis. To establish an easy-to-use algorithm for the identification of LN false positivity, a decision tree including clinically meaningful parameters was generated. In total, 77 (59.7%) and 52 (40.3%) patients were included in the LUAD and SQCA groups, respectively. SQCA histology, non-G1 tumors, and tumor SUVmax > 12.65 were identified as independent predictors of LN false positivity in the preoperative staging. The corresponding ORs and their 95% CIs were 3.35 [1.10-10.22], p = 0.0339; 4.60 [1.06-19.94], p = 0.0412; and 2.76 [1.01-7.55], and p = 0.0483. The preoperative identification of false-positive LNs is an important aspect of the treatment regimen for patients with operable lung cancer; thus, these preliminary findings should be further evaluated in larger patient cohorts.

Resultados de la estadificación clínica ganglionar mediastínica del cáncer pulmonar quirúrgico: datos de la cohorte prospectiva nacional del Grupo Español de Cirugía Torácica Videoasistida / Results in mediastinal lymph node staging of surgical lung cancer: Data from the prospective cohort of the Spanish Video-Assisted Thoracic Surgery Group

Introducción: El objetivo del estudio es valorar el rendimiento diagnóstico de la tomografía computarizada (TC) y la tomografía por emisión de positrones (PET) en la estadificación clínica mediastínica del cáncer pulmonar quirúrgico según los datos de la cohorte prospectiva del Grupo Español de Cirugía Torácica Videoasistida (GEVATS). Métodos: Se han analizado 2.782 pacientes intervenidos por carcinoma pulmonar primario. Se ha estudiado el acierto diagnóstico en la estadificación mediastínica (cN2). Se ha realizado un análisis bivariante y multivariante de los factores que influyen en el acierto. Se ha estudiado el riesgo de pN2 inesperado en los factores con los que se recomienda una prueba invasiva de estadificación: cN1, tumor central o tamaño mayor de 3cm. Resultados: El acierto global de la TC y PET en conjunto es del 82,9% con VPP y VPN de 0,21 y 0,93. En tumores mayores de 3cm y a mayor SUVmax del mediastino, el acierto es menor, OR de 0,59 (0,44 – 0,79) y 0,71 (0,66 – 0,75), respectivamente. En el abordaje VATS el acierto es mayor, OR de 2,04 (1,52 – 2,73). El riesgo de pN2 inesperado aumenta con el número de los factores cN1, tumor central o tamaño mayor de 3cm: entre el 4,5% (0 factores) y 18,8% (3 factores), pero no hay diferencias significativas con la realización de prueba invasiva. Conclusiones: La TC y PET en conjunto tienen un elevado valor predictivo negativo. Su acierto global es menor en tumores mayores de 3cm y SUVmax del mediastino elevado, y mayor en el abordaje VATS. El riesgo de pN2 inesperado es mayor si cN1, tumor central o mayor de 3cm y no varía significativamente con prueba invasiva. (AU)

Objectives: The objective of this study was to assess the diagnostic performance of combined computerised tomography (CT) and positron emission tomography (PET) in mediastinal staging of surgical lung cancer based on data obtained from the prospective cohort of the Spanish Group for Video-Assisted Thoracic Surgery (GEVATS). Methods: A total of 2782 patients underwent surgery for primary lung carcinoma. We analysed diagnostic success in mediastinal lymph node staging (cN2) using CT and PET. Bivariate and multivariate analyses were performed of the factors involved in this success. The risk of unexpected pN2 disease was analysed for cases in which an invasive testing is recommended: cN1, the tumour centrally located or the tumour diameter >3cm. Results: The overall success of CT together with PET was 82.9% with a positive predictive value of 0.21 and negative predictive value of 0.93. If the tumour was larger than 3cm and for each unit increase in mediastinal SUVmax, the probability of success was lower with OR 0.59 (0.44–0.79) and 0.71 (0.66–0.75), respectively. In the video-assisted thoracic surgery (VATS) approach, the probability of success was higher with OR 2.04 (1.52–2.73). The risk of unexpected pN2 increased with the risk factors cN1, the tumour centrally located or the tumour diameter >3cm: from 4.5% (0 factors) to 18.8% (3 factors) but did not differ significantly as a function of whether invasive testing was performed. Conclusions: CT and PET together have a high negative predictive value. The overall success of the staging is lower in the case of tumours >3cm and high mediastinal SUVmax, and it is higher when VATS is performed. The risk of unexpected pN2 is higher if the disease is cN1, the tumour centrally located or the tumour diameter >3cm but does not vary significantly as a function of whether patients have undergone invasive testing. (AU)

Lymph Node Log-Odds Ratio Accurately Defines Prognosis in Resectable Non-Small Cell Lung Cancer.

OBJECTIVES: The ratio of positive and resected lymph nodes (LN ratio) has been shown to be prognostic in non-small cell lung cancer (NSCLC). Contrary to the LN ratio, calculating the LN log-odds ratio (LN-LOR) additionally considers the total number of resected lymph nodes. We aim to evaluate LN-LOR between positive and resected lymph nodes as a prognostic factor in operable NSCLC. METHODS: Patients with NSCLC who underwent curative intent lobectomy treated at two high-volume centers were retrospectively studied. LN-LOR was dichotomized according to impact on OS and further combined with N descriptors and correlated with clinical variables and survival. RESULTS: 944 patients were included. Cut-off analysis revealed that an LN-LOR of -0.34 significantly discriminated patients according to OS (p < 0.001, chi-squared test 41.26). When combined with N1 and N2 descriptors, LN-LOR low risk (median OS not reached and 83 months) and LN-LOR high-risk patients (median OS 50 and 59 months) had similar survival irrespective of the anatomical location of the positive lymph nodes. Multivariable Cox regression analysis revealed that age (HR 1.02, 95% CI 1.001-1.032), sex (male, HR 1.65, 95% CI 1.25-2.19), histological subtype (HR 2.11, 95% CI 1.35-3.29), pathological stage (HR 1.23, 95% CI 1.01-1.45) and LN-LOR risk groups (low risk, HR 0.48, 95% CI 0.32-0.72) were independent prognostic factors for OS. CONCLUSIONS: This retrospective two-center analysis shows that LN-LOR is significantly associated with OS in resectable NSCLC and might better reflect the biological behavior of the disease, regardless of anatomical lymph node locations. This finding may additionally support the value of extensive LN dissection.

The absence of lymph nodes removed (pNx status) impacts survival in patients with lung cancer treated surgically.

OBJECTIVES: We aimed to study the clinical significance of the lack of lymph node assessment (pNx status) and its impact on survival in non-small-cell lung cancer patients. METHODS: We retrospectively analysed the Polish Lung Cancer Study Group database. pNx status was defined as 0 lymph nodes removed. We included 17,192 patients. RESULTS: A total of 1080 patients (6%) had pNx status. pNx patients were more likely to be younger, be female, have a different pT distribution, have squamous cell carcinoma, undergo open thoracotomy, be operated on in non-academic hospitals, and have a lower rate of some comorbidities. pNx was more likely to be cN0 than pN1 and pN2 but less likely than pN0 (p < 0.001). pNx patients were less likely to undergo preoperative invasive mediastinal diagnostics than pN1 and pN2 patients but more likely than pN0 patients (p < 0.001). Overall, the five-year overall survival rates were 64%, 45%, 32% and 50% for pN0, pN1, pN2 and pNx, respectively. In pairwise comparisons, all pN descriptors differed significantly from each other (all p < 0.0001 but pNx vs. pN1 p = 0.016). The placement of the pNx survival curve and survival rate depended on histopathology, surgical approach and pT status. In multivariable analysis, pNx was an independent prognostic risk factor (HR = 1.37, 95%CI: 1.23-1.51, p < 0.01). CONCLUSION: The resection of lymph nodes in lung cancer remains a crucial step in the surgical treatment of this disease. The survival of pNx patients is similar to that of pN1 patients. pNx survival curve placement depends on the other variables which could be useful in clinical decisions.

A machine learning tool to improve prediction of mediastinal lymph node metastases in non-small cell lung cancer using routinely obtainable [18F]FDG-PET/CT parameters.

BACKGROUND: In patients with non-small cell lung cancer (NSCLC), accuracy of [18F]FDG-PET/CT for pretherapeutic lymph node (LN) staging is limited by false positive findings. Our aim was to evaluate machine learning with routinely obtainable variables to improve accuracy over standard visual image assessment. METHODS: Monocentric retrospective analysis of pretherapeutic [18F]FDG-PET/CT in 491 consecutive patients with NSCLC using an analog PET/CT scanner (training + test cohort, n = 385) or digital scanner (validation, n = 106). Forty clinical variables, tumor characteristics, and image variables (e.g., primary tumor and LN SUVmax and size) were collected. Different combinations of machine learning methods for feature selection and classification of N0/1 vs. N2/3 disease were compared. Ten-fold nested cross-validation was used to derive the mean area under the ROC curve of the ten test folds ("test AUC") and AUC in the validation cohort. Reference standard was the final N stage from interdisciplinary consensus (histological results for N2/3 LNs in 96%). RESULTS: N2/3 disease was present in 190 patients (39%; training + test, 37%; validation, 46%; p = 0.09). A gradient boosting classifier (GBM) with 10 features was selected as the final model based on test AUC of 0.91 (95% confidence interval, 0.87-0.94). Validation AUC was 0.94 (0.89-0.98). At a target sensitivity of approx. 90%, test/validation accuracy of the GBM was 0.78/0.87. This was significantly higher than the accuracy based on "mediastinal LN uptake > mediastinum" (0.7/0.75; each p < 0.05) or combined PET/CT criteria (PET positive and/or LN short axis diameter > 10 mm; 0.68/0.75; each p < 0.001). Harmonization of PET images between the two scanners affected SUVmax and visual assessment of the LNs but did not diminish the AUC of the GBM. CONCLUSIONS: A machine learning model based on routinely available variables from [18F]FDG-PET/CT improved accuracy in mediastinal LN staging compared to established visual assessment criteria. A web application implementing this model was made available.

[Radiologic evaluation of lymph nodes in cancer patients]. / Bildgebende Diagnostik von Lymphknoten bei Verdacht auf Tumorbefall.

BACKGROUND: In solid tumors, the detection of locoregional lymph node metastases is of decisive importance not only for the prognosis but also for selecting the correct treatment. Various noninvasive imaging methods or, classically, lymph node dissection are available for this purpose. OBJECTIVE: This article presents the general principles of noninvasive lymph node diagnostics and discusses the value of the clinically available imaging modalities, ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET). In addition, recent new technical developments of each modality are highlighted. MATERIAL AND METHODS: Literature search and summary of the clinical and scientific experience of the authors. RESULTS: The available imaging procedures are divided into (1) morphological (US, CT, MRI) and (2) functional modalities (PET, special MRI). The former capture structural lymph node parameters, such as size and shape, while the latter address properties that go beyond morphology (e.g. glucose metabolism). The high diagnostic accuracy required for future treatment algorithms will require a combination of both aspects. DISCUSSION/CONCLUSION: Currently, none of the available modalities have sufficient accuracy to replace lymph node dissection in all oncological scenarios. One of the major challenges for interdisciplinary oncological research is to define the optimal interaction between imaging and lymph node dissection for different malignancies and tumor stages.

Results in mediastinal lymph node staging of surgical lung cancer: Data from the prospective cohort of the Spanish Video-Assisted Thoracic Surgery Group.

OBJECTIVES: The objective of this study was to assess the diagnostic performance of combined computerised tomography (CT) and positron emission tomography (PET) in mediastinal staging of surgical lung cancer based on data obtained from the prospective cohort of the Spanish Group for Video-Assisted Thoracic Surgery (GEVATS). METHODS: A total of 2782 patients underwent surgery for primary lung carcinoma. We analysed diagnostic success in mediastinal lymph node staging (cN2) using CT and PET. Bivariate and multivariate analyses were performed of the factors involved in this success. The risk of unexpected pN2 disease was analysed for cases in which an invasive testing is recommended: cN1, the tumour centrally located or the tumour diameter >3 cm. RESULTS: The overall success of CT together with PET was 82.9% with a positive predictive value of 0.21 and negative predictive value of 0.93. If the tumour was larger than 3 cm and for each unit increase in mediastinal SUVmax, the probability of success was lower with OR 0.59 (0.44-0.79) and 0.71 (0.66-0.75), respectively. In the video-assisted thoracic surgery (VATS) approach, the probability of success was higher with OR 2.04 (1.52-2.73). The risk of unexpected pN2 increased with the risk factors cN1, the tumour centrally located or the tumour diameter >3 cm: from 4.5% (0 factors) to 18.8% (3 factors) but did not differ significantly as a function of whether invasive testing was performed. CONCLUSIONS: CT and PET together have a high negative predictive value. The overall success of the staging is lower in the case of tumours >3 cm and high mediastinal SUVmax, and it is higher when VATS is performed. The risk of unexpected pN2 is higher if the disease is cN1, the tumour centrally located or the tumour diameter >3 cm but does not vary significantly as a function of whether patients have undergone invasive testing.

Radiomics Signature Using Manual Versus Automated Segmentation for Lymph Node Staging of Bladder Cancer.

BACKGROUND: Bladder cancer (BC) treatment algorithms depend on accurate tumor staging. To date, computed tomography (CT) is recommended for assessment of lymph node (LN) metastatic spread in muscle-invasive and high-risk BC. However, the diagnostic efficacy of radiologist-evaluated CT imaging studies is limited. OBJECTIVE: To evaluate the performance of quantitative radiomics signatures for detection of LN metastases in BC. DESIGN, SETTING, AND PARTICIPANTS: Of 1354 patients with BC who underwent radical cystectomy (RC) with lymphadenectomy who were screened, 391 with pathological nodal staging (pN0: n = 297; pN+: n = 94) were included and randomized into training (n = 274) and test (n = 117) cohorts. Pelvic LNs were segmented manually and automatically. A total of 1004 radiomics features were extracted from each LN and a machine learning model was trained to assess pN status using histopathology labels as the ground truth. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Radiologist assessment was compared to radiomics-based analysis using manual and automated LN segmentations for detection of LN metastases in BC. Statistical analysis was performed using the receiver operating characteristics curve method and evaluated in terms of sensitivity, specificity, and area under the curve (AUC). RESULTS AND LIMITATIONS: In total, 1845 LNs were manually segmented. Automated segmentation correctly located 361/557 LNs in the test cohort. Manual and automatic masks achieved an AUC of 0.80 (95% confidence interval [CI] 0.69-0.91; p = 0.64) and 0.70 (95% CI: 0.58-0.82; p = 0.17), respectively, in the test cohort compared to radiologist assessment, with an AUC of 0.78 (95% CI 0.67-0.89). A combined model of a manually segmented radiomics signature and radiologist assessment reached an AUC of 0.81 (95% CI 0.71-0.92; p = 0.63). CONCLUSIONS: A radiomics signature allowed discrimination of nodal status with high diagnostic accuracy. The model based on manual LN segmentation outperformed the fully automated approach. PATIENT SUMMARY: For patients with bladder cancer, evaluation of computed tomography (CT) scans before surgery using a computer-based method for image analysis, called radiomics, may help in standardizing and improving the accuracy of assessment of lymph nodes. This could be a valuable tool for optimizing treatment options.

Clinical value of regional lymph node sorting in gastric cancer.

BACKGROUND: Increasing evidence have shown that regional lymph node metastasis is a critical prognostic factor in gastric cancer (GC). In addition, lymph node dissection is a key factor in determining the appropriate treatment for GC. However, the association between the number of positive lymph nodes and area of lymph node metastasis in GC remains unclear. AIM: To investigate the clinical value of regional lymph node sorting after radical gastrectomy for GC. METHODS: This study included 661 patients with GC who underwent radical gastrectomy at Tianjin Medical University General Hospital between January 2012 and June 2020. The patients were divided into regional sorting and non-sorting groups. Clinicopathological data were collected and retrospectively reviewed to determine the differences in the total number of lymph nodes and number of positive lymph nodes between the groups. Independent sample t-tests were used for intergroup comparisons. Continuous variables that did not conform to a normal distribution were expressed as median (interquartile range), and the Mann-Whitney U test was used for inter-group comparisons. RESULTS: There were no significant differences between the groups in terms of the surgical method, tumor site, immersion depth, and degree of differentiation. The total number of lymph nodes was significantly higher in the regional sorting group (n = 324) than in the non-sorting group (n = 337) (32.5 vs 21.2, P < 0.001). There was no significant difference in the number of positive lymph nodes between the two groups. A total of 212 patients with GC had lymph node metastasis in the lymph node regional sorting group, including 89 (41.98%) cases in the first dissection station and 123 (58.02 %) cases in the second dissection station. Binary and multivariate logistic regression results showed that the number of positive lymph nodes (P < 0.001) was an independent risk factor for lymph node metastases at the second dissection station. CONCLUSION: Regional sorting of lymph nodes after radical gastrectomy may increase the number of detected lymph nodes, thereby improving the reliability and accuracy of lymph node staging in clinical practice.

Improved Accuracy of Lymph Node Staging and Long-Term Survival Benefit in Colorectal Cancer With Ex Vivo Arterial Methylene Blue Infiltration.

Introduction: Ex vivo methylene blue (MB) injection into the main supplying arteries of the colorectal specimen after surgical removal is an uncomplicated technique to support lymph node harvest during pathological evaluation. The primary aim of this randomized, interventional, bicentric trial was to evaluate the impact of MB injection on lymph node yield, with secondary aims assessing the accuracy of lymph node staging and the effect on 5-year overall survival for patients undergoing resection of colorectal cancer. Methods: In the study period between December 2013 and August 2015, 200 colorectal resections were performed at two independent onco-surgery centers of Hungary. Following surgical resection, each specimen was randomly assigned either to the control (standard pathological work-up) or to the MB staining group before formaldehyde fixation. Patient-level surgical and clinical data were retrieved from routinely collected clinical datasets. Survival status data were obtained from the National Health Insurance Fund of Hungary. Results: A total of 162 specimens, 82 in the control and 80 in the MB groups, were included for analysis. Baseline characteristics were equally distributed among study groups, except for specimen length. Both the median of total number of lymph nodes retrieved (control 11 ± 8 [0-33] nodes vs. MB 14 ± 6 [0-42] nodes; p < 0.01), and the ratio of cases with at least 12 removed lymph nodes (36/82, 43.9% vs. 53/80, 66.3%; p < 0.01) were higher in the MB group. The rate of accurate lymph node staging was non-significantly improved. As for rectal cancer, nodal staging accuracy (16/31, 51.6% vs. 23/30, 76.7%; p = 0.04) and the proportion with minimum 12 lymph node retrieval (7/31, 22.6%, vs. 18/30, 60%; p < 0.01) was improved by MB injection. In Mantel-Cox regression, a statistically significant survival benefit with methylene blue injection at 5 years post-surgery was proven (51.2% vs. 68.8%; p = 0.04). Conclusion: In our experience, postoperative ex vivo arterial methylene blue injection appears to be an uncomplicated technique, improving lymph node yield and decreasing the chance of insufficient nodal staging. The technique might also associate with a 5-year overall survival benefit.

Developing and validating a prognostic nomogram for ovarian clear cell carcinoma patients: A retrospective comparison of lymph node staging schemes with competing risk analysis.

Purpose: Lymph node (LN) involvement is a key factor in ovarian clear cell carcinoma (OCCC) although, there several indicators can be used to define prognosis. This study examines the prognostic performances of each indicator for OCCC patients by comparing the number of lymph nodes examined (TNLE), the number of positive lymph nodes (PLN), lymph node ratio (LNR), and log odds of metastatic lymph nodes (LODDS). Methods: 1,300 OCCC patients who underwent lymphadenectomy between 2004 and 2015 were extracted from the Surveillance Epidemiology and End Results (SEER) database. Primary outcomes were Overall Survival (OS) and the cumulative incidence of Cancer-Specific Survival (CSS). Kaplan-Meier's and Fine-Gray's tests were implemented to assess OS and CSS rates. After conducting multivariate analysis, nomograms using OS and CSS were constructed based upon an improved LN system. Each nomograms' performance was assessed using Receiver Operating Characteristics (ROC) curves, calibration curves, and the C-index which were compared to traditional cancer staging systems. Results: Multivariate Cox's regression analysis was used to assess prognostic factors for OS, including age, T stage, M stage, SEER stage, and LODDS. To account for the CSS endpoint, a proportional subdistribution hazard model was implemented which suggested that the T stage, M stage, SEER stage, and LNR are all significant. This enabled us to develop a LODDS-based nomogram for OS and a LNR-based nomogram for CSS. C-indexes for both the OS and CSS nomograms were higher than the traditional American Joint Committee on Cancer (AJCC), 8th edition, staging system. Area Under the Curve (AUC) values for predicting 3- and 5-year OS and CSS between nomograms also highlighted an improvement upon the AJCC staging system. Calibration curves also performed with consistency, which was verified using a validation cohort. Conclusions: LODDS and LNR may be better predictors than N stage, TNLE, and PLNs. For OCCC patients, both the LODDS-based and LNR-based nomograms performed better than the AJCC staging system at predicting OS and CSS. However, further large sample, real-world studies are necessary to validate the assertion.

Estadiaje ganglionar en el adenocarcinoma gástrico / Lymph node stage in gastric adenocarcinoma

Resumen Objetivos: El sistema linfático del estómago es complejo y multidireccional, siendo difícil predecir el patrón de diseminación linfática en el adenocarcinoma (ADC) gástrico. Los objetivos de este trabajo son determinar si el analizar los grupos ganglionares de la pieza quirúrgica por separado tiene implicaciones en el estadiaje, además estudiar la afectación de diferentes grupos ganglionares. Materials y Método: Estudio observacional retrospectivo de pacientes intervenidos de gastrectomía y linfadenectomía con intención curativa por ADC en un hospital de referencia (2017-2021).,_Se han comparado aquellos pacientes cuya pieza quirúrgica se estudió en su totalidad (grupo A) con aquellos en los que se separaron los grupos ganglionares para su análisis (grupo B). En el grupo B, se ha analizado la afectación ganglionar de diferentes grupos ganglionares en base a la localización tumoral y el estadio pT. Resultados: Se incluyeron 150 pacientes. La media de ganglios analizados fue significativamente mayor cuando se separaron los grupos ganglionares (grupo B) (24,01 respecto a 20,49). La afectación ganglionar fue del 45,8%, 58,3% y 55,5% en los tumores de tercio superior, medio e inferior respectivamente, y los grupos difirieron en base a la localización tumoral. El riesgo de afectación ganglionar fue significativamente mayor y hubo más grupos ganglionares perigástricos afectos cuanto mayor era el estadio pT. Conclusiones: Separar los grupos ganglionares previo a su análisis aumenta el número de ganglios analizados mejorando el estadiaje ganglionar. Existen diferentes rutas de drenaje linfático dependiendo de la localización tumoral y la afectación ganglionar aumenta de forma paralela al estadio pT.

Objectives: The lymphatic system of the stomach is complex and multidirectional, making it difficult to predict the pattern of lymphatic spread in gastric adenocarcinoma (GAC). The aim of this paper is to determine if analyzing the lymph node groups of the surgical specimen separately has implications in the pathological staging, as well as to study the involvement rate of different lymph node groups. Material and Method: Retrospective observational study of patients who underwent curative intent gastrectomy and lymphadenectomy for GAC in a reference hospital (2017-2021). Those patients whose surgical specimen was studied as a whole (group A) were compared with those in whom the lymph node groups were separated by surgeons before analysis (group B). In group B, the involvement of different lymph node groups was analyzed based on tumor location and pT stage. Results: 150 patients were included. The mean number of lymph nodes analyzed was significantly higher when the lymph node groups were separately analyzed (group B) (24.01 compared to 20.49). Lymph node involvement was 45.8%, 58.3%, and 55.5% in tumors of the upper, middle, and lower third, respectively, and the involved groups differed depending on the tumor location. The higher the pT stage was, the risk of lymph node involvement was significantly higher and there were more perigastric lymph node groups affected. Conclusions: Separating lymph node groups prior to their analysis increases the number of lymph nodes analyzed and therefore improves lymph node staging. There are different lymphatic drainage routes depending on the tumor location and lymph node involvement increases in parallel with the pT stage.