Assessment of programmed death-ligand 1 expression in primary tumors and paired lymph node metastases of gastric adenocarcinoma.

BACKGROUND: Anti-programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) immunotherapy has demonstrated promising results on gastric cancer (GC). However, PD-L1 can express differently between metastatic sites and primary tumors (PT). AIM: To compare PD-L1 status in PT and matched lymph node metastases (LNM) of GC patients and to determine the correlation between the PD-L1 status and clinicopathological characteristics. METHODS: We retrospectively reviewed 284 GC patients who underwent D2-gastrectomy. PD-L1 was evaluated by immunohistochemistry (clone SP142) using the combined positive score. All PD-L1+ PT staged as pN+ were also tested for PD-L1 expression in their LNM. PD-L1(-) GC with pN+ served as the comparison group. RESULTS: Among 284 GC patients included, 45 had PD-L1+ PT and 24 of them had pN+. For comparison, 44 PD-L1(-) cases with pN+ were included (sample loss of 4 cases). Of the PD-L1+ PT, 54.2% (13/24 cases) were also PD-L1+ in the LNM. Regarding PD-L1(-) PT, 9.1% (4/44) had PD-L1+ in the LNM. The agreement between PT and LNM had a kappa value of 0.483. Larger tumor size and moderate/severe peritumoral inflammatory response were associated with PD-L1 positivity in both sites. There was no statistical difference in overall survival for PT and LNM according to the PD-L1 status (P = 0.166 and P = 0.837, respectively). CONCLUSION: Intra-patient heterogeneity in PD-L1 expression was observed between the PT and matched LNM. This disagreement in PD-L1 status may emphasize the importance of considering different tumor sites for analyses to select patients for immunotherapy.

Real-world retrospective study of prostate-specific antigen and safety assessment with darolutamide plus androgen deprivation therapy for metastasis hormone-sensitive prostate cancer.

Background: ARASENS has demonstrated the efficacy and safety for darolutamide (DARO) with androgen deprivation therapy (ADT) plus docetaxel in metastasis hormone-sensitive prostate cancer (mHSPC). There is a lack of reports for DARO with ADT in mHSPC though the regimen is used in clinical from time to time. Moreover, recent studies have supported the importance of early and rapid prostate-specific antigen (PSA) reduction, which correlates with reduced disease progression and improved survival in patients with mHSPC. This study aims to evaluate PSA reduction as a primary endpoint for DARO with ADT in the treatment of mHSPC and to evaluate the real-world short-term PSA control of DARO with ADT from two leading medical centers in China. Methods: We retrospectively reviewed the clinical records of patients with mHSPC receiving ADT and DARO (600 mg, b.i.d.). The collection of data spanned from March 1, 2022, to July 31, 2023. The main observation indicators were PSA level and drug-related adverse events (AE) after medication. PSA levels were closely monitored prior to treatment initiation and at 2-week intervals, as well as at 1, 3, and 6 months after the initiation of treatment. We also conducted an analysis to determine the proportion of patients achieving a PSA reduction of 50% or more (PSA50) and 90% or more (PSA90) as well as the percentage of patients with a notable decrease in PSA level to 0.2 ng/mL and PSA nadir of ≤0.02 ng/mL. Results: Fifty-one patients were included in the study, with a median age of 73 years. At diagnosis of HSPC, the majority of patients had a Gleason score ≥8 (n=40, 78.40%) and a median baseline PSA level of 88 ng/mL. Approximately 45.1% (n=23) of patients had a Charlson Comorbidity Index over 1 and were receiving one or more nontumor-related treatments. The median follow-up time was 9.3 months (range, 1.16-15.8 months). The median reductions in PSA levels compared to baseline were 84.37%, 91.48%, 94.67% and 99.81% at 2 weeks, 1 month, 3 months and 6 months after administration of DARO with ADT, respectively. The median time to PSA50, PSA90, significant PSA reduction (PSA <0.2 ng/mL), and PSA nadir (PSA <0.02 ng/mL) was 0.97, 1.27, 1.98, and 2.08 months, respectively. AE mainly included fatigue (two patients) and arm pain (one patient), all of which were grade I or II AE. No grade III or AE were observed. Conclusions: For treating prostate cancer, DARO with ADT has good early efficacy, demonstrating prompt and substantial control of PSA levels, with a favorable safety profile.

Exploratory Assessment of Galectin-1, -3, and -9 in Non-Small Cell Lung Cancer.

Galectins play a pivotal role in lung cancer oncogenic pathways, influencing apoptosis, angiogenesis, and tumor metastasis. Biomarkers that diagnose, prognose, and guide cancer treatment are crucial, with galectins having the biomarker potential for non-small cell lung cancer (NSCLC). Using enzyme-linked immunosorbent assay (ELISA), we assessed serum galectin-1, -3, and -9 levels in NSCLC patients. A retrospective chart review was performed to examine patient demographics, cancer stage, tumor biology, cancer treatment, and patient outcomes. Galectin levels were then compared across these factors. In this exploratory analysis, galectin-3 levels were significantly lower in patients with squamous cell lung cancer (p = 0.0019) and in patients exposed to chemotherapy (p = 0.0375). Galectin-1 levels were significantly lower in patients with previous metastasis but had no correlation with future metastasis. Abnormal galectin-1 levels were significantly correlated with decreased overall survival (OS) in NSCLC (p = 0.0357) and specifically in patients with surgically resectable NSCLC (p = 0.0112). However, abnormal galectin-1 levels were not found to correlate with decreased OS in multivariable analysis (p = 0.0513). These findings may have clinical implications as galectin-3 inhibitors are in trials for NSCLC. Additionally, they suggest that galectin-1 has potential as a prognostic marker for surgically resectable NSCLC.

Pathologic Assessment and Staging of Multiple Non-Small Cell Lung Carcinomas: A Paradigm Shift with the Emerging Role of Molecular Methods.

Non-small cell lung carcinomas (NSCLCs) commonly present as 2 or more separate tumors. Biologically, this encompasses 2 distinct processes: separate primary lung carcinomas (SPLCs), representing independently arising tumors, and intrapulmonary metastases (IPMs), representing intrapulmonary spread of a single tumor. The advent of computed tomography imaging has substantially increased the detection of multifocal NSCLCs. The strategies and approaches for distinguishing between SPLCs and IPMs have evolved significantly over the years. Recently, genomic sequencing of somatic mutations has been widely adopted to identify targetable alterations in NSCLC. These molecular techniques have enabled pathologists to reliably discern clonal relationships among multiple NSCLCs in clinical practice. However, a standardized approach to evaluating and staging multiple NSCLCs using molecular methods is still lacking. Here, we reviewed the historical context and provided an update on the growing applications of genomic testing as a clinically relevant benchmark for determining clonal relationships in multiple NSCLCs, a practice we have designated "comparative molecular profiling." We examined the strengths and limitations of the morphology-based distinction of SPLCs vs IPMs and highlighted pivotal clinical and pathologic insights that have emerged from studying multiple NSCLCs using genomic approaches as a gold standard. Lastly, we suggest a practical approach for evaluating multiple NSCLCs in the clinical setting, considering the varying availability of molecular techniques.

Utility of UV Signature Mutations in the Diagnostic Assessment of Metastatic Head and Neck Carcinomas of Unknown Primary.

BACKGROUND: Metastatic carcinoma of unknown primary origin to the head and neck lymph nodes (HNCUP) engenders unique diagnostic considerations. In many cases, the detection of a high-risk human papillomavirus (HR-HPV) unearths an occult oropharyngeal squamous cell carcinoma (SCC). In metastatic HR-HPV-independent carcinomas, other primary sites should be considered, including cutaneous malignancies that can mimic HR-HPV-associated SCC. In this context, ultraviolet (UV) signature mutations, defined as ≥ 60% C→T substitutions with ≥ 5% CC→TT substitutions at dipyrimidine sites, identified in tumors arising on sun exposed areas, are an attractive and underused tool in the setting of metastatic HNCUP. METHODS: A retrospective review of institutional records focused on cases of HR-HPV negative HNCUP was conducted. All cases were subjected to next generation sequencing analysis to assess UV signature mutations. RESULTS: We identified 14 HR-HPV negative metastatic HNCUP to either the cervical or parotid gland lymph nodes, of which, 11 (11/14, 79%) had UV signature mutations, including 4 (4/10, 40%) p16 positive cases. All UV signature mutation positive cases had at least one significant TP53 mutation and greater than 20 unique gene mutations. CONCLUSION: The management of metastatic cutaneous carcinomas significantly differs from other HNCUP especially metastatic HR-HPV-associated SCC; therefore, the observation of a high percentage of C→T with CC →TT substitutions should be routinely incorporated in next generation sequencing reports of HNCUP. UV mutational signatures testing is a robust diagnostic tool that can be utilized in daily clinical practice.

Depth of Invasion Assessment in Laryngeal Glottic Carcinoma: A Preoperative Imaging Approach for Prognostication.

OBJECTIVE: The prognostic value of depth of invasion (DOI) in oral squamous cell cancer carcinoma and cutaneous melanoma is well established, while there is a lack of reports investigating the role of DOI in laryngeal cancer. This study aims to explore the association of glottic cancer DOI with other established pathological risk factors and nodal metastasis and evaluate the feasibility of measuring DOI preoperatively using tomographic imaging. METHODS: The medical records of glottic cancer patients treated between 2015 and 2020 in a single tertiary referral center were screened retrospectively. Pathologically measured DOI (pDOI) value was also reviewed and registered. Preoperative computer tomography (CT) was used to obtain the radiological DOI (rDOI) measured by two dedicated radiologists. Their inter-rated agreement was assessed and the correlation between pDOI and rDOI was calculated. pDOI association with the main pathology report features was assessed with univariable analysis. Cox univariable and multivariable models were used to explore the role of pDOI on survival. RESULTS: Ninety-one patients had pDOI data available, of which 59 also had rDOI data. A strong concordance between the two radiologists was found (concordance correlation coefficient = 0.96); rDOI and pDOI were highly and significantly correlated (R = 0.85; p < 0.001). pDOI was significantly higher in patients with perineural invasion (PNI; p < 0.001), lymphovascular invasion (LVI; p < 0.001), and nodal metastasis (p < 0.001). pDOI was associated with disease-free survival at univariable analysis (p = 0.04) while it did not show a significant impact (p = 0.10) at multivariable analysis. CONCLUSION: Glottic carcinoma DOI correlates with PNI, LVI, and nodal metastasis and it can be reliably assessed in a preoperative setting using CT imaging. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Accuracy of radiomics in the diagnosis and preoperative high-risk assessment of endometrial cancer: a systematic review and meta-analysis.

Background: With the increasing use of radiomics in cancer diagnosis and treatment, it has been applied by some researchers to the preoperative risk assessment of endometrial cancer (EC) patients. However, comprehensive and systematic evidence is needed to assess its clinical value. Therefore, this study aims to investigate the application value of radiomics in the diagnosis and treatment of EC. Methods: Pubmed, Cochrane, Embase, and Web of Science databases were retrieved up to March 2023. Preoperative risk assessment of EC included high-grade EC, lymph node metastasis, deep myometrial invasion status, and lymphovascular space invasion status. The quality of the included studies was appraised utilizing the RQS scale. Results: A total of 33 primary studies were included in our systematic review, with an average RQS score of 7 (range: 5-12). ML models based on radiomics for the diagnosis of malignant lesions predominantly employed logistic regression. In the validation set, the pooled c-index of the ML models based on radiomics and clinical features for the preoperative diagnosis of endometrial malignancy, high-grade tumors, lymph node metastasis, lymphovascular space invasion, and deep myometrial invasion was 0.900 (95%CI: 0.871-0.929), 0.901 (95%CI: 0.877-0.926), 0.906 (95%CI: 0.882-0.929), 0.795 (95%CI: 0.693-0.897), and 0.819 (95%CI: 0.705-0.933), respectively. Conclusions: Radiomics shows excellent accuracy in detecting endometrial malignancies and in identifying preoperative risk. However, the methodological diversity of radiomics results in significant heterogeneity among studies. Therefore, future research should establish guidelines for radiomics studies based on different imaging sources. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=364320 identifier CRD42022364320.

Surgical and Interventional Management of Lung Metastasis: Surgical Assessment, Resection, Ablation, Percutaneous Interventions.

The lungs are the second most common site of metastases for colorectal cancer after the liver. Pulmonary metastases can be identified at the time of diagnosis of the primary tumor, or metachronously. About 20% of patients with colorectal cancer will develop pulmonary metastases. The best options for treatment include a multidisciplinary treatment approach consisting of surgical resection whenever possible, and chemotherapy. Surgical options most often include minimally invasive segmentectomy or wedge resection, while patients unable to have surgery may benefit from radio frequency ablation or radiation treatment. Prognosis is dependent on preoperative carcinoembryonic antigen level, number, and location of metastatic lesions, and resectability of primary tumor. Overall, pulmonary metastases are best treated by complete resection whenever possible.

Treatment response assessment to chemotherapy with bevacizumab for colorectal liver metastasis by contrast-enhanced ultrasound.

Background: Though contrast-enhanced ultrasound (CEUS) perfusion parameters have been approved to be potential indicators for response to chemotherapy in solid tumors, their ability in assessment of colorectal liver metastasis (CRLM) to chemotherapy with bevacizumab (Bev) has rarely been investigated. Methods: From March 2021 to May 2022, 115 consecutive CRLM patients with CEUS pre- and post-2 months' chemotherapy with Bev were prospectively enrolled. One target lesion per patient underwent CEUS quantitative analysis with SonoLiver software. Rise time, time-to-peak, mean transit time, maximal intensity (IMAX), and area under the time-intensity curve (AUC) were assessed with region of interest (ROI) selected on whole lesion, lesion periphery, and internal lesion, respectively. The reduction and ratio of post- to pre-treatment in parameters were investigated in development cohort (n=89) and validated in internal validation cohort (n=26) according to the chronological order. Results: With modified Response Evaluation Criteria in Solid Tumor as reference, 48, 14 responders and 41, 12 non-responders were included in development and validation cohort, respectively. Significantly smaller values of IMAX and AUC on ROIwhole, ROIperipheral, and ROIinternal, were observed post-treatment in development cohort (all P<0.05). In predicting treatment response, the influence of ROI selection was observed when using ∆IMAX and ∆AUC, while no influence was observed using ratios. Areas under the receiver operating characteristic curve (AUROCs) for ∆IMAX and ∆AUC on ROIperipheral were 0.939 (0.867-0.979), 0.951 (0.883-0.985), and 0.917 (0.740-0.988), 0.923 (0.748-0.990) in development and validation cohort, respectively. For ratios of IMAX and AUC, AUROCs were 0.976 (0.919-0.997), 0.938 (0.865-0.978), and 0.899 (0.717-0.982), 0.982 (0.836-1.000) in development and validation cohort, respectively. Conclusions: IMAX and AUC showed significant reductions in responders, and different analyses ROIs influence the performance of ∆IMAX and ∆AUC in response assessment. Parameters derived from ROI peripheral exhibited the most promising results in predicting treatment response.

Assessment of bone turnover markers and DXA parameters to predict bone metastasis progression during zoledronate treatment: a single-center experience.

Bone metastases (BM) are a serious cancer complication, potentially causing substantial morbidity. Among the clinical issues related to BM, there is the lack of specific tools for early diagnosis and prognosis. We explored whether combining bone turnover markers (BTM) with dual-energy X-ray absorptiometry (DXA) assessment could identify early BM progression and risk of skeletal-related events (SREs) during zoledronate treatment. Before the initiation of zoledronate (T0) and after six months of treatment (T1), serum levels of five BTM were measured, and patients (N = 47) underwent DXA evaluation. Standard radiological imaging was performed to assess bone tumor response to medical anti-cancer treatment. High tumor burden in bone correlated with higher serum CTX (p = 0.007) and NTX (p = 0.005) at baseline. Low concentrations of OPG at T0 predicted BM progression with a sensitivity and specificity of 63% and 77%, respectively, when a cutoff of 5.2 pmol/l was used; such a predictive meaning was stronger in patients with lytic BM (sensitivity: 88%, specificity: 80%; p = 0.0006). As for the risk of SREs, we observed an association between low baseline OC (p = 0.04) and OPG (p = 0.08) and the onset of any-time SREs, whereas an increase in OPG over time was associated with reduced risk of on-study events (p = 0.03). Moreover, a statistically significant correlation emerged between low baseline lumbar T-score and femur BMD and on-study SREs (p < 0.001 in both instances). These findings suggest that addition of DXA to BTM dosage could help stratifying the risk of SREs at the time of BM diagnosis but does not enhance our capability of detecting bone progression, during zoledronate treatment.

Navigating Post-Operative Outcomes: A Comprehensive Reframing of an Original Graded Prognostic Assessment in Patients with Brain Metastases.

BACKGROUND: Graded Prognostic Assessment (GPA) has been proposed for various brain metastases (BMs) tailored to the primary histology and molecular profiles. However, it does not consider whether patients have been operated on or not and does not include surgical outcomes as prognostic factors. The residual tumor burden (RTB) is a strong predictor of overall survival. We validated the GPA score and introduced "volumetric GPA" in the largest cohort of operated patients and further explored the role of RTB as an additional prognostic factor. METHODS: A total of 630 patients with BMs between 2007 and 2020 were included. The four GPA components were analyzed. The validity of the original score was assessed using Cox regression, and a modified index incorporating RTB was developed by comparing the accuracy, sensitivity, specificity, F1-score, and AUC parameters. RESULTS: GPA categories showed an association with survival: age (p < 0.001, hazard ratio (HR) 2.9, 95% confidence interval (CI) 2.5-3.3), Karnofsky performance status (KPS) (p < 0.001, HR 1.3, 95% CI 1.2-1.5), number of BMs (p = 0.019, HR 1.4, 95% CI 1.1-1.8), and the presence of extracranial manifestation (p < 0.001, HR 3, 95% CI 1.6-2.5). The median survival for GPA 0-1 was 4 months; for GPA 1.5-2, it was 12 months; for GPA 2.5-3, it was 21 months; and for GPA 3.5-4, it was 38 months (p < 0.001). RTB was identified as an independent prognostic factor. A cut-off of 2 cm3 was used for further analysis, which showed a median survival of 6 months (95% CI 4-8) vs. 13 months (95% CI 11-14, p < 0.001) for patients with RTB > 2 cm3 and <2 cm3, respectively. RTB was added as an additional component for a modified volumetric GPA score. The survival rates with the modified GPA score were: GPA 0-1: 4 months, GPA 1.5-2: 7 months, GPA 2.5-3: 18 months, and GPA 3.5-4: 34 months. Both scores showed good stratification, with the new score showed a trend towards better discrimination in patients with more favorable prognoses. CONCLUSION: The prognostic value of the original GPA was confirmed in our cohort of patients who underwent surgery for BM. The RTB was identified as a parameter of high prognostic significance and was incorporated into an updated "volumetric GPA". This score provides a novel tool for prognosis and clinical decision making in patients undergoing surgery. This method may be useful for stratification and patient selection for further treatment and in future clinical trials.

Multiplex Imaging Reveals Novel Subcellular, Microenvironmental, and Racial Patterns of MRTFA/B Activation in Invasive Breast Cancers and Metastases.

Breast cancer progression and metastasis involve the action of multiple transcription factors in tumors and in the cells of the tumor microenvironment (TME) and understanding how these transcription factors are coordinated can guide novel therapeutic strategies. Myocardin related transcription factors A and B (MRTFA/B) are two related transcription factors that redundantly control cancer cell invasion and metastasis in mouse models of breast cancer, but their roles in human cancer are incompletely understood. Here, we used a combination of multiplexed immunofluorescence and bioinformatics analyses to show that MRTFA/B are concurrently activated in tumor cells, but they show distinct patterns of expression across different histological subtypes and in the TME. Importantly, MRTFA expression was elevated in metastatic tumors of African American patients, who disproportionately die from breast cancer. Interestingly, in contrast to publicly available mRNA expression data, MRTFA was similarly expressed across estrogen receptor (ER) positive and negative breast tumors, while MRTFB expression was highest in ER+ breast tumors. Furthermore, MRTFA was specifically expressed in the perivascular antigen presenting cells (APCs) and its expression correlated with the expression of the immune checkpoint protein V-set immunoregulatory receptor (VSIR). These results provide unique insights into how MRTFA and MRTFB can promote metastasis in human cancer, into the racial disparities of their expression patterns, and their function within the complex breast cancer TME.

An [18F]FDG PET/3D-ultrashort echo time MRI-based radiomics model established by machine learning facilitates preoperative assessment of lymph node status in non-small cell lung cancer.

OBJECTIVES: To develop an [18F]FDG PET/3D-UTE model based on clinical factors, three-dimensional ultrashort echo time (3D-UTE), and PET radiomics features via machine learning for the assessment of lymph node (LN) status in non-small cell lung cancer (NSCLC). METHODS: A total of 145 NSCLC patients (training, 101 cases; test, 44 cases) underwent whole-body [18F]FDG PET/CT and chest [18F]FDG PET/MRI were enrolled. Preoperative clinical factors and 3D-UTE, CT, and PET radiomics features were analyzed. The Mann-Whitney U test, LASSO regression, and SelectKBest were used for feature extraction. Five machine learning algorithms were used to establish prediction models, which were evaluated by the area under receiver-operator characteristic (ROC), DeLong test, calibration curves, and decision curve analysis (DCA). RESULTS: A prediction model based on random forest, consisting of four clinical factors, six 3D-UTE, and six PET radiomics features, was used as the final model for PET/3D-UTE. The AUCs of this model were 0.912 and 0.791 in the training and test sets, respectively, which not only showed different degrees of improvement over individual models such as clinical, 3D-UTE, and PET (AUC-training = 0.838, 0.834, and 0.828, AUC-test = 0.756, 0.745, and 0.768, respectively) but also achieved the similar diagnostic efficacy as the optimal PET/CT model (AUC-training = 0.890, AUC-test = 0.793). The calibration curves and DCA indicated good consistency (C-index, 0.912) and clinical utility of this model, respectively. CONCLUSION: The [18F]FDG PET/3D-UTE model based on clinical factors, 3D-UTE, and PET radiomics features using machine learning methods could noninvasively assess the LN status of NSCLC. CLINICAL RELEVANCE STATEMENT: A machine learning model of 18F-fluorodeoxyglucose positron emission tomography/ three-dimensional ultrashort echo time could noninvasively assess the lymph node status of non-small cell lung cancer, which provides a novel method with less radiation burden for clinical practice. KEY POINTS: • The 3D-UTE radiomics model using the PLS-DA classifier was significantly associated with LN status in NSCLC and has similar diagnostic performance as the clinical, CT, and PET models. • The [18F]FDG PET/3D-UTE model based on clinical factors, 3D-UTE, and PET radiomics features using the RF classifier could noninvasively assess the LN status of NSCLC and showed improved diagnostic performance compared to the clinical, 3D-UTE, and PET models. • In the assessment of LN status in NSCLC, the [18F]FDG PET/3D-UTE model has similar diagnostic efficacy as the [18F]FDG PET/CT model that incorporates clinical factors and CT and PET radiomics features.

Assessment of whole-body MRI including diffusion-weighted sequences in the initial staging of breast cancer patients at high risk of metastases in comparison with PET-CT: a prospective cohort study.

OBJECTIVE: The aim of this study was to assess the diffusion-weighted whole-body-MRI (WBMRI) in the initial staging of breast cancer at high risk of metastases in comparison with positron emission tomography (PET)-CT. METHODS: Forty-five women were prospectively enrolled. The inclusion criteria were female gender, age >18, invasive breast cancer, an initial PET-CT, and a performance status of 0-2. The exclusion criteria were contraindication to WB-MRI and breast cancer recurrence. The primary outcome was the concordance of WB-MRI and PET-CT in the diagnosis of distant metastases, whereas secondary outcomes included their concordance for the primary tumor and regional lymph nodes (LN), as well as the agreement of WB-MRI interpretation between two radiologists. RESULTS: The mean age was 51.2 years with a median size of the primary tumor of 30 mm. Concordance between the two modalities was almost perfect for metastases staging, all sites included (k = 0.862), with excellent interobserver agreement. The accuracy of WB-MRI for detecting regional LN, distant LN, lung, liver, or bone metastases ranged from 91 to 96%. In 2 patients, WB-MRI detected bone metastases that were overlooked by PET-CT. WB-MRI showed a substantial agreement with PET-CT for staging the primary tumor, regional LN status, and stage (k = 0.766, k = 0.756, and k = 0.785, respectively) with a high interobserver agreement. CONCLUSION: WB-MRI including DWI could be a reliable and reproducible examination in the initial staging of breast cancer patients at high risk of metastases, especially for bone metastases and therefore could be used as a surrogate to PET-CT. CLINICAL RELEVANCE STATEMENT: Whole-body-MRI including DWI is a promising technique for detecting metastases in the initial staging of breast cancer at high risk of metastases. KEY POINTS: Whole-body-MRI (WB-MRI) was effective for detecting metastases in the initial staging of 45 breast cancer patients at high risk of metastases in comparison with PET-CT. Concordance between WB-MRI and PET-CT was almost perfect for metastases staging, all sites included, with excellent interobserver agreement. The accuracy of WB-MRI for detecting bone metastases was 92%.

Clinical features and imaging examination assessment of cervical lymph nodes for thyroid carcinoma.

BACKGROUNDS: The purpose of this study is to investigate the relationship between clinical characteristics and cervical lymph node metastasis (LNM) in patients with thyroid carcinoma, as well as estimate the preoperative diagnosis values of ultrasound (US) and contrast enhanced computed tomography (CECT) examinations on the neck for detection of cervical LNM in thyroid carcinoma. METHODS: A retrospective analysis of 3 026 patients with surgically proven thyroid carcinoma was conducted. Patients' clinical characteristics, including gender, age, tumor size, bilateral lesions, multifocality, adenomatous nodules, Hashimoto's thyroiditis (HT), and extrathyroidal extension, were collected to explore their association with cervical LNM in thyroid carcinoma. Preoperative assessments for central lymph node metastasis (CLNM) and lateral lymph node metastasis (LLNM) were conducted through US and CECT. The diagnostic value of US, CECT and US combined with CECT for detection of LNM located in various cervical compartments was estimated based on the pathological results. RESULTS: The risk of cervical LNM was higher in thyroid cancer patients who were male, age < 55 years old, tumor size > 10 mm, bilateral lesions, and extrathyroidal extension, while multifocality, adenomatous nodules and HT had no significant effect on LNM. US, CECT and US combined with CECT all had a higher sensitivity to LLNM (93.1%, 57.8%, 95.4%) than to CLNM (32.3%, 29.0%, 43.4%). US and CECT had a high specificity to both CLNM and LLNM (94.3-97.8%). CONCLUSION: Preoperative clinical characteristics and imaging examinations on patients with thyroid carcinoma are crucial to the evaluation of cervical lymph nodes and conducive to individualizing surgical treatments by clinicians. US combined with CECT are superior to single US or CECT alone in detection of CLNM and LLNM.

Assessment of aggressive bladder cancer mutations in plasma cell-free DNA.

Background and aims: The spatial and temporal genetic heterogeneity of bladder cancer (BC) makes challenging to find specific drivers of metastatic disease, thus preventing to determine those BC patients at high risk of tumor progression. Our aim was to identify DNA mutations providing aggressive behavior to bladder tumors and analyze them in patients' cell-free DNA (cfDNA) during their follow-up after radical cystectomy (RC) in order to monitor tumor evolution. Methods: Six BC patients who underwent RC and presented disease progression during their follow-up were included. Next-generation sequencing was used to determine somatic mutations in several primary tumor and metastatic specimens from each patient. Shared DNA mutations between primary bladder tumor and metastatic sites were identified in cfDNA samples through droplet digital PCR. Results: Besides BC genetic heterogeneity, specific mutations in at least one of these genes -TERT, ATM, RB1, and FGFR3- were found in primary tumors and their metastases in all patients. These mutations were also identified in the patients' cfDNA at different follow-up time points. Additionally, the dynamic changes of these mutations in cfDNA allowed us to determine tumor evolution in response to treatment. Conclusion: The analysis of BC mutations associated with poor prognosis in plasma cfDNA could be a valuable tool to monitor tumor evolution, thus improving the clinical management of BC patients.

Nasopharyngeal malignant melanoma masquerading in the gallbladder: the importance of histological assessment.

Metastatic melanoma of the gallbladder is a rare entity that is often diagnosed late, leading to a poor prognosis. The disease may present insidiously as acute cholecystitis or remain asymptomatic. Optimal management remains unclear but surgical resection is considered the mainstay of treatment for this condition. We report the case of a 47-year-old man who suffered a protracted course of generalised abdominal symptoms eventually culminating in a diagnosis of acute cholecystitis. Following an emergency laparoscopic cholecystectomy, the histology revealed a melanoma with an unknown primary. Subsequently this was traced to the nasopharynx. Because of the presence of concurrent liver metastasis, systemic immunotherapy with palliative intent was commenced following a multidisciplinary team discussion. This case highlights the importance of sending clinical specimens for histological analysis. We argue against selectively choosing which specimens to send for histology because radiological and/or intraoperative macroscopic inspection of resected tissue alone can result in a missed diagnosis.

Risk assessment in pT1 colorectal cancer.

Colorectal cancer (CRC) is a common malignancy worldwide and tumour stage is closely related to clinical outcome. A small but significant proportion of submucosal-invasive (ie, pT1) CRC are associated with regional lymph node metastases (LNM) and a worse prognosis. The likelihood of LNM in pT1 CRC needs to be balanced against the operative risk and costs of surgical resection when determining the best patient management. A wide range of histopathological and clinical factors may affect LNM risk in this setting. This script provides a comprehensive overview of the tumour and patient-associated features that have been linked to LNM risk in pT1 CRC. Some of the features are well established within the literature and are included in published guidelines, while others are novel and emerging in nature. Odds ratios for LNM that are associated with key predictive features are provided where appropriate, and published models developed as an aid to the calculation of LNM risk are discussed.

Assessment of the albumin-bilirubin score in breast cancer patients with liver metastasis after surgery.

Objective: This study aims to investigate the potential prognostic value of albumin-bilirubin (ALBI) score in breast cancer patients with liver metastasis after surgery. Methods: This was a retrospective study of 178 breast cancer patients with liver metastasis after surgery. ALBI score was calculated by the following formula: (log10 bilirubin × 0.66) - (albumin × 0.085). The optimal cutoff value of ALBI score was assessed by X-tile. The clinical influence of ALBI score on survival outcomes using Kaplan-Meier method, Log-rank test, Cox proportional hazards regression model. The calibration curves, decision curve analysis and time-dependent ROC curve were used to assess the predictive performance of the nomogram's models. Results: The classifications of 178 breast cancer patients with liver metastasis after surgery were as follows: low ALBI score group (＜-3.36) vs. high ALBI score group (≥-3.36). The Cox proportional hazards regression model indicated that ALBI score was a potential predictor. Kaplan-Meier survival curve performed that the median disease free survival (p = 0.0029) and overall survival (p＜0.0001) in low ALBI score group were longer than in high ALBI score group. The ALBI-based nomograms had good predictive performance. Conclusions: The ALBI score has high prognostic ability for survival time in breast cancer with liver metastasis after surgery. These models will be valuable in discriminating patients at high risks of liver metastasis.