The 8th AJCC classification is inferior to a new neck stage based on intraparotid lymph node in parotid gland cancer.

BACKGROUND: Lymph node (LN) status is an important prognostic factor for parotid gland cancer (PGC). This study aimed to analyze the impact of extranodal extension (ENE) of intraparotid LN and LN metastasis burden on survival in PGC. METHODS: Patients with surgically treated PGC and at least one metastatic cervical LN were retrospectively enrolled. Primary outcome variables were distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS). The impact of ENE and LN metastasis burden was assessed using the Cox model. RESULTS: A total of 292 patients were included. ENE in cervical or intraparotid LN was not associated with DMFS, DSS, or OS. Intraparotid LN metastasis had a significant impact on prognosis, and the presence of only one metastatic intraparotid LN offered an approximately 1.5-fold risk of distant metastasis. Prognostic models based on the number of positive LNs (1 vs. 2-3 vs. 4+) were superior to the AJCC N stage in terms of DMFS, DSS, and OS. CONCLUSIONS: ENE of cervical or intraparotid LN has a limited effect on the prognosis of PGC, and the number of positive LNs is better than the AJCC N stage in LN status evaluation.

Immune infiltration at the primary tumor is associated with clinical outcome of patients with extranodal extension of lymph node metastasis in oral cancer.

BACKGROUND: Extranodal extension (ENE) of lymph node metastasis is one of the most reliable prognostic indicators for patients with locally advanced oral cancer. Although multiple reports have found a close relationship between immune infiltration of tumors and patient clinical outcomes, its association with ENE is unknown. METHODS: We identified 234 human papillomavirus-negative (HPV-) oral cavity squamous cell carcinoma (OSCC) patients in The Cancer Genome Atlas and investigated the immune infiltration profiles of primary tumors and their association with survival. RESULTS: Hierarchical clustering analysis clearly classified the overall immune infiltration status in OSCC into high immune or low immune groups. The combination of ENE positivity and low immune infiltration was strongly associated with poor overall survival (OS) compared to the combination of ENE positivity and high immune infiltration [hazard ratio 2.04 (95 %CI, 1.08-3.83); p = 0.024]. The immune infiltration status was not associated with OS rates in patients with ENE-negative or node negative tumors. CONCLUSION: Overall Immune infiltration at the primary site was significantly associated with clinical outcome of OSCC patients with ENE.

[Clinical characteristics and prognostic factors of breast cancer patients with tumor deposits in the ipsilateral axillary region].

Objective: To investigate the clinicopathologic features and prognostic factors of breast cancer patients with tumor deposits in the ipsilateral axillary region. Methods: We retrospectively analyzed the clinicopathologic data and follow-up results of 155 patients with breast cancer diagnosed for the first time and complicated with tumor deposits in the ipsilateral axillary region in the Department of Thyroid-Breast-Vascular Surgery of Xijing Hospital from January 2008 to September 2018. Kaplan-Meier method was used for survival analysis. Log rank test was used for the univariate analysis of prognostic factors, and Cox regression was used for multivariate analysis. Results: The median disease free survival (DFS), median distant metastasis free survival (DMFS), and median overall survival (OS) of the 155 patients were 52.0 months, 66.6 months, and 102.2 months, respectively. The 5-year and 10-year DFS rates were 45.7% and 23.1%, the 5-year and 10-year DMFS rates were 56.9% and 28.9%, and the 5-year and 10-year OS rates were 79.3% and 46.0%, respectively. Multivariate Cox regression analysis showed that family tumor history (HR=0.362, 95% CI: 0.140-0.937), clinical T stage (T3: HR=3.508, 95% CI: 1.380-8.918; T4: HR=2.220, 95% CI: 1.076-4.580), estrogen/progesterone receptor status (HR=0.476, 95% CI: 0.261-0.866), number of tumor deposits (HR=1.965, 95% CI:1.104-3.500) and neoadjuvant chemotherapy (HR=1.961, 95% CI: 1.032-3.725) were independent influencing factors for DFS. Molecular subtype [human epidermal growth factor receptor-2(HER-2) positive and hormone receptor negative: HR=7.862, 95% CI: 3.189-19.379], number of tumor deposits (HR=2.155, 95% CI: 1.103-4.212), neoadjuvant chemotherapy (HR=5.002, 95% CI: 2.300-10.880) and radiotherapy (HR=2.316, 95% CI: 1.005-5.341) were independent influencing factors of DMFS. Histological grade (HR=4.362, 95% CI: 1.932-9.849), estrogen/progesterone receptor expression (HR=0.399, 95% CI: 0.168-0.945), HER-2 expression (HR=2.535, 95% CI: 1.114-5.768) and neoadjuvant chemotherapy (HR=4.080, 95% CI: 1.679-9.913) were independent influencing factors of OS. Conclusions: The presence of tumor deposits weakens the influence of axillary lymph node status and distant metastases on the prognosis of breast cancer patients. Therefore, a clinicopathological staging system taking into account tumor deposits should be developed. Since the number of tumor deposits affects the risk of recurrence and metastasis of breast cancer patients, we recommend that the number of tumor deposits should be reported in detail in the pathological report after breast cancer surgery.

Lymphoma and Other Lymph Node Pathologies Among Adult Patients with Lymphadenopathy in Abakaliki, Nigeria.

INTRODUCTION: Lymphadenopathy is usually due to benign or malignant conditions. It can also be local or systemic in distribution and can involve peripheral or deep-seated lymph nodes. This study aimed to determine the prevalence of lymphoma and the distribution pattern of lymph node pathologies among adult patients who presented with lymphadenopathy and its relationship with age and sex. METHODS: A retrospective study was conducted, and a record of all cases of lymphadenopathy with histological diagnosis over 5-year period (January 2017 to December 2021) was extracted from Departments of Anatomical Pathology of Alex Ekwueme Federal University Teaching Hospital, Abakaliki. The data generated were analyzed using Statistical Package for Social Sciences (SPSS) software, version 26. RESULTS: One hundred and ninety results were extracted with an age range of 18 to 94 years and a mean age of 41 ± 16 years. They were made up of 75 (39.5%) males and 115 (60.5%) females, with a male-to-female ratio of 1:1.5. The prevalence of lymphoma was 50.0% (95/190). Thirty-five (18.4%) were Hodgkin's lymphoma (HL), while 60 (31.6%) were non-Hodgkin's lymphoma (NHL). Other pathologies manifested by cases of lymphadenopathy include metastatic tumor deposits (38 (20%)), reactive lymphoid hyperplasia (29 (15.3%)), and tuberculous lymphadenitis (18 (9.5%)). Others include sinus histiocytosis (4 (2.1%)), dermatopathic lymphadenitis (5 (2.6%)), and Castleman's disease (1 (0.5%)). CONCLUSION: About half of all patients who presented with lymphadenopathy were lymphoma with a high prevalence of 50%, and the majority were NHL. Other major causes of lymphadenopathy were metastatic tumor deposits, reactive lymphoid hyperplasia, and tuberculous lymphadenitis. Any case of lymphadenopathy should be properly investigated early for effective management.

Presence of tumor deposits is a strong indicator of poor outcome in patients with stage III colorectal cancers undergoing radical surgery.

BACKGROUND: Tumor deposits (TDs) are emerging as an adverse prognostic factor in colorectal cancers (CRCs). However, TDs are somewhat neglected in the current staging system. It has been proposed either to add the TD count to the number of metastatic lymph nodes or to consider TDs as distant metastases; however, the scientific basis for these proposals seems questionable. This study aimed to investigate a new staging system. METHODS: A total of 243 consecutive patients with stage III CRC who were undergoing curative resection and adjuvant chemotherapy were included. Each substage of stage III TNM was split according to the absence or presence of TDs. Receiver operating characteristic (ROC) curves and bootstrap methods were used to compare the current vs the new competing staging system in terms of oncologic outcome prediction. RESULTS: A high rate of TDs was recorded (124 cases [51%]). TDs were correlated with other adverse prognostic indicators, particularly vascular and perineural invasions, and showed a negative correlation with the number of removed lymph nodes, suggesting a possible multimodal origin. In addition, TDs were confirmed to have a negative impact on oncologic outcome, regardless of their counts. Compared with the current staging system, the new classification displayed higher values at survival ROC analysis, a significantly better stratification of patients, and effective identification of patients at high risk of recurrence. CONCLUSIONS: TDs negatively affect the prognosis in CRCs. A revision of the staging system could be useful to optimize treatments. The proposed new classification is easy to implement and more accurate than the current one. This study was registered online on the ClinicalTrials.gov website under the following identifier: NCT05923450.

Tumour deposits are independently associated with recurrence in colon cancer.

AIM: Tumour deposits are focal aggregates of cancer cells in pericolic fat and mesentery, distinct from vessels, nerves and lymphatics. Their presence upstages lymph node negative patients but is ignored in lymph node positive patients. We investigated the clinicopathological factors associated with tumour deposits and their impact on recurrence in lymph node positive and negative patients. METHOD: Clinicopathological variables were collected from the medical records of patients with Stage I-III colon cancer who underwent resection in 2017-2019. Pathology was reviewed by a gastrointestinal pathologist. Patients with rectal cancer, metastasis, and concurrent malignancy were excluded. RESULTS: Tumour deposits were noted in 69 (9%) of 770 patients. They were associated with the presence of lymph node metastasis, advanced T category, poorly differentiated tumours, microsatellite stable subtype and lymphovascular and perineural invasion (p < 0.05). The presence of tumour deposits (hazard ratio 2.48, 95% CI 1.49-4.10) and of lymph node metastasis (hazard ratio 3.04, 95% CI 1.72-5.37) were independently associated with decreased time to recurrence. There was a weak correlation (0.27) between the number of tumour deposits and the number of positive lymph nodes. CONCLUSION: Tumour deposits are associated with more advanced disease and high-risk pathological features. The presence of tumour deposits and lymph node metastasis were found to be independent risk factors for decreased time to recurrence. A patient with both lymph node metastasis and tumour deposits is more than twice as likely to have recurrence compared with a patient with only lymph node metastasis. Tumour deposits independently predict recurrence and should not be ignored in lymph node positive patients.

The significance of the presence of extranodal extension in the metastatic node of differentiated thyroid cancer: a proposal for modification in the American Thyroid Association (ATA) risk stratification.

BACKGROUND: Multiple factors contribute to recurrences in differentiated thyroid cancers (DTC). Though the nodal size and number of positive nodes along with the presence of extranodal extension (ENE) have been mentioned in the present ATA risk stratification, the weightage given for ENE seems inadequate compared to the former two. METHODOLOGY: Factors predicting recurrences were analysed in this retrospective study of patients with DTC operated in a tertiary care centre. Based on our findings, we propose a modification in the present risk stratification. We have done so by comparing with existing risk stratification for fit and discrimination of this system. RESULTS: Out of 1428 patients, 859 (60.2%) patients had pathological nodal metastases (pN +) with ENE being present in 26.8% of these. The recurrence rate was 6.4% (92 patients). Recurrence rates in patients with ≤ 5 nodes without ENE, > 5 nodes without ENE, ≤ 5 nodes with ENE and > 5 nodes with ENE were 2.7%, 1.3%, 8.3% and 10.3%, respectively. Recurrence rates in patients with 0.2-3 cm without ENE, 0.2-3 cm with ENE and > 3 cm with/without ENE were 1.8%, 8.5% and 13.4%, respectively. A modified risk stratification incorporating ENE and excluding the number of metastatic nodes was proposed. The modified risk stratification had a better fit than the present system in terms of higher C index and lower AIC. CONCLUSIONS: Extranodal extension in differentiated thyroid cancer had the maximum influence on recurrence risk (recurrence-free survival) in our cohort. The prognostic impact of ENE supersedes the number of positive nodes in the risk of recurrence.

Defining the role of multiparametric MRI in predicting prostate cancer extracapsular extension.

OBJECTIVES: To identify the predictive factors of prostate cancer extracapsular extension (ECE) in an institutional cohort of patients who underwent multiparametric MRI of the prostate prior to radical prostatectomy (RP). PATIENTS AND METHODS: Overall, 126 patients met the selection criteria, and their medical records were retrospectively collected and analysed; 2 experienced radiologists reviewed the imaging studies. Logistic regression analysis was conducted to identify the variables associated to ECE at whole-mount histology of RP specimens; according to the statistically significant variables associated, a predictive model was developed and calibrated with the Hosmer-Lomeshow test. RESULTS: The predictive ability to detect ECE with the generated model was 81.4% by including the length of capsular involvement (LCI) and intraprostatic perineural invasion (IPNI). The predictive accuracy of the model at the ROC curve analysis showed an area under the curve (AUC) of 0.83 [95% CI (0.76-0.90)], p < 0.001. Concordance between radiologists was substantial in all parameters examined (p < 0.001). Limitations include the retrospective design, limited number of cases, and MRI images reassessment according to PI-RADS v2.0. CONCLUSION: The LCI is the most robust MRI factor associated to ECE; in our series, we found a strong predictive accuracy when combined in a model with the IPNI presence. This outcome may prompt a change in the definition of PI-RADS score 5.

Clinical Significance and Prognostic Implications of Discontinuous Growth Pattern in Esophageal Adenocarcinoma: A Multi-Institutional Study.

The significance of discontinuous growth (DG) of the tumor to include tumor deposits and intramural metastasis in esophageal adenocarcinoma (EAC) is unclear. Esophagectomy specimens from 151 treatment-naïve and 121 treated patients with EAC were reviewed. DG was defined as discrete (≥2 mm away) tumor foci identified at the periphery of the main tumor in the submucosa, muscularis propria, and/or periadventitial tissue. Patients' demographics, clinicopathologic parameters, and oncologic outcomes were compared between tumors with DG versus without DG. DGs were identified in 16% of treatment-naïve and 29% of treated cases ( P =0.01). Age, gender, and tumor location were comparable in DG+ and DG- groups. For the treatment-naïve group, DG+ tumors were larger with higher tumor grade and stage and more frequent extranodal extension, lymphovascular/perineural invasion, and positive margin. Patients with treated tumors presented at higher disease stages with higher rates of recurrence and metastasis compared with treatment-naïve patients. In this group, DG was also associated with TNM stage and more frequent lymphovascular/perineural spread and positive margin, but not with tumor size, grade, or extranodal extension. In multivariate analysis, in all patients adjusted for tumor size, lymphovascular involvement, margin, T and N stage, metastasis, neoadjuvant therapy status, treatment year, and DG, DG was found to be an independent adverse predictor of survival outcomes in EAC. DG in EAC is associated with adverse clinicopathologic features and worse patient outcomes. DG should be considered throughout the entire clinicopathologic evaluation of treatment-naïve and treated tumors as well as in future staging systems.

The prognostic effect of radiological extranodal extension in HPV-positive oropharyngeal squamous cell carcinomas: a retrospective cohort analysis.

PURPOSE: Radiological extranodal extension (rENE) is a well-known negative prognosticator in head and neck squamous cell carcinoma (HNSCC). However, controversy remains regarding the prognostic effect of rENE in HPV-positive oropharyngeal SCCs (OPSCC). This single-center retrospective cohort analysis assessed the prognostic role of rENE in an HPV + OPSCC population and tried to validate a recently proposed modification of the TNM8 N-classification. METHODS: 129 patients with HPV + OPSCC, of whom 106 cN + patients, were included. Radiological imaging (CT, MRI or both) was reanalyzed by a senior head and neck radiologist. Overall survival (OS), disease-free survival (DFS), locoregional recurrence-free survival (LRFS), and disease-specific survival (DSS) were evaluated. Cox proportional hazard models were used for estimating hazard ratios (HR). RESULTS: A non-significant trend towards better outcomes in the rENE- group, as compared to the rENE + population, was observed for 5 year OS [80.99% vs 68.70%, HR: 2.05, p = 0.160], 5 year RFS [78.81% vs 67.87%, HR: 1.91, p = 0.165], 5 year DFS [77.06% vs 60.16%, HR: 2.12, p = 0.0824] and 5 year DSS [88.83% vs 81.93%, HR: 2.09, p = 0.195]. OS declined with ascending levels of rENE (p = 0.020). Multivariate analysis identified cT-classification and smoking as independent negative predictors for OS/DFS. The proposed modification of the TNM8 N-classification could not be validated. CONCLUSIONS: Although rENE could not be identified as an independent negative prognosticator for outcome in our HPV + OPSCC population, outcomes tend to deteriorate with increasing rENE.

MRI-predicted extramural vascular invasion and tumour deposit are main predictors of disease-free survival in patients undergoing surgical resection for rectal cancer.

BACKGROUND: MRI is crucial in staging patients with rectal cancer and planning treatment. The aim was to analyse the prognostic role of MRI-predicted tumour deposits and/or extramural vascular invasion (mrTD/EMVI) in a cohort of patients with rectal cancer undergoing surgical resection, with selective neoadjuvant chemoradiotherapy (nCRT). METHOD: Retrospective analysis of a single-centre cohort of consecutive patients with rectal cancer undergoing low anterior resection or abdominoperineal excision between 2008 and 2020. Unit policy was selective nCRT for MRI-predicted threatened or involved circumferential resection margin (mrCRM), or radiologically involved pelvic sidewall nodes. The primary outcome was disease-free survival. Secondary outcomes were rates of local recurrence, distant recurrence and overall survival. RESULTS: A total of 314 patients were analysed. Median age was 65 years (female/male: 114/200). A total of 54/314 (17%) had nCRT and 35 patients (11%) underwent abdominoperineal excision. Median follow-up was 64 months. Overall, local recurrence was detected in 18/314 (5.7%) and distant recurrence in 45/314 (14.3%). In patients not receiving nCRT (n = 260), local recurrence was detected in 11/260 (4.2%) and distant recurrence in 35/260 (13.5%). Disease-free survival was 80.5% at 5 years. Specifically, disease-free survival was 89% in mrTD/EMVI-negative and mrCRM-negative, 67% in mrTD/EMVI-positive and mrCRM-negative, and 64% in the mrCRM-positive rectal cancer (log-rank, P < 0.001). On multivariable Cox-regression analysis mrTD/EMVI was the only MRI variable associated with disease-free survival (hazard ratio 2.95; P < 0.001). CONCLUSION: mrTD/EMVI is a major prognostic indicator. Rectal cancer patients with mrCRM-negative and mrTD/EMVI-negative have excellent long-term outcomes with surgery alone. Patients with mrTD/EMVI-positive should be selectively stratified for neoadjuvant treatments in future clinical trials.

Prognostic effect of categorized tumor deposits in gastric cancer: A single-center retrospective study.

BACKGROUND: Tumor deposits are defined as all types of isolated cancer lesions without lymphocyte aggregates considered part of the lymph node. Tumor deposits have been reported as a negative prognostic factor. However, the survival significance of categorized tumor deposits is uncertain, particularly in gastric cancer. This study aimed to investigate the prognostic difference among categorized tumor deposits. METHODS: Patients who underwent gastrectomy for gastric cancer were enrolled. All tumor deposits were categorized into irregular nodule, irregular nodule star, smooth nodule, and vascular/neural invasion. There are some cases with more than 2 categorized tumor deposits. These cases were categorized as tumor deposit complex in the following analysis. We performed survival analysis between the patients with and without tumor deposits, and compared the survival among each categorized tumor deposit. RESULTS: Of 868 patients, there were 96 (11.1%) and 772 (88.9%) patients with and without tumor deposits. Vascular/neural invasion, smooth nodule, irregular nodule, irregular nodule star, and the tumor deposits complex was observed in 6 (6.3%), 15 (15.6%), 43 (44.8%), 1 (1.0%), and 31 (32.3%) patients. Patients with tumor deposits displayed poorer survival than those without; the 3-year overall survival: tumor deposits negative = 87.0%, tumor deposits positive = 53.2% (P < .001). Survival analysis revealed tumor deposits can be a prognostic risk factor (hazard ratio: 1.9854, 95% confidence interval: 1.393-2.830, P < .01). Irregular nodule and the tumor deposits complex demonstrated the worst prognosis (irregular nodule 3-year overall survival: 51.2%, tumor deposits complex 3-year overall survival: 41.9%, P = .001), whereas smooth nodule demonstrated better prognosis (smooth nodule 3-year overall survival: 80%). CONCLUSION: Tumor deposits exerted a negative survival effect in gastric cancer. Irregular nodule and the tumor deposits complex displayed a strong prognostic effect.

Validation of a Clinical Calculator Predicting Freedom From Colon Cancer Recurrence After Surgery on the Basis of Molecular and Clinical Variables.

BACKGROUND: The Memorial Sloan Kettering clinical calculator for estimating the likelihood of freedom from colon cancer recurrence on the basis of clinical and molecular variables was developed at a time when testing for microsatellite instability was performed selectively, based on patient age, family history, and histologic features. Microsatellite stability was assumed if no testing was done. OBJECTIVE: This study aimed to validate the calculator in a cohort of patients who had all been tested for microsatellite instability. DESIGN: Retrospective cohort analysis. SETTINGS: Comprehensive cancer center. PATIENTS: This study included consecutive patients who underwent curative resection for stage I, II, or III colon cancer between 2017 and 2019. INTERVENTION: Universal testing of mircrosatellite phenotype in all cases. MAIN OUTCOME MEASURES: The calculator's predictive accuracy was assessed using the concordance index and a calibration plot of predicted versus actual freedom from recurrence at 3 years after surgery. For a secondary sensitivity analysis, the presence of a tumor deposit(s) (disease category N1c) was considered equivalent to one positive lymph node (category N1a). RESULTS: With a median follow-up of 32 months among survivors, the concordance index for the 745 patients in the cohort was 0.748 (95% CI, 0.693-0.801), and a plot of predicted versus observed recurrences approached the 45° diagonal, indicating good discrimination and calibration. In the secondary sensitivity analysis for tumor deposits, the concordance index was 0.755 (95% CI, 0.700-0.806). LIMITATIONS: This study was limited by its retrospective, single-institution design. CONCLUSIONS: These results, based on inclusion of actual rather than imputed microsatellite stability status and presence of tumor deposits, confirm the predictive accuracy and reliability of the calculator. See Video Abstract . VALIDACIN DE UNA CALCULADORA CLNICA QUE PREDICE LA AUSENCIA DE RECURRENCIA POSTQUIRURGICA DEL CNCER DE COLON SOBRE LA BASE DE VARIABLES MOLECULARES Y CLNICAS: ANTECEDENTES:La calculadora clínica del Memorial Sloan Kettering para la estimación de la probabilidad de ausencia de recurrencia del cáncer de colon sobre la base de variables clínicas y moleculares, se desarrolló en un momento en que las pruebas para la inestabilidad de microsatélites se realizaban de forma selectiva, basadas en la edad del paciente, los antecedentes familiares y las características histológicas. Se asumía la estabilidad micro satelital si no se realizaba ninguna prueba.OBJETIVO:El objetivo de este estudio fue validar la calculadora en una cohorte de pacientes a los que se les había realizado la prueba de inestabilidad de microsatélites.DISEÑO:Análisis de cohorte retrospectivo.AJUSTE:Centro integral de cáncer.PACIENTES:Pacientes consecutivos con cáncer de colon que fueron sometidos a resección curativa por cáncer de colon en estadios I, II o III entre los años 2017 y 2019.PRINCIPALES MEDIDAS DE RESULTADO:La precisión predictiva de la calculadora fue evaluada mediante el índice de concordancia y un gráfico de calibración de la ausencia de recurrencia predecida versus la real a los 3 años tras la cirugía. A los efectos de un análisis secundario de sensibilidad, la presencia de depósito(s) tumoral(es) (categoría de enfermedad N1c) se consideró equivalente a un ganglio linfático positivo (categoría N1a).RESULTADOS:Con una mediana de seguimiento de 32 meses entre los supervivientes, el índice de concordancia para los 745 pacientes de la cohorte fue de 0,748 (intervalo de confianza del 95 %, 0,693 a 0,801), y una gráfica de recurrencias previstas versus observadas se acercó a la diagonal de 45°, indicando una buena discriminación y calibración. En el análisis secundario de sensibilidad para depósitos tumorales, el índice de concordancia fue de 0,755 (intervalo de confianza del 95 %, 0,700 a 0,806).LIMITACIONES:Diseño retrospectivo, institución única.CONCLUSIONES:Estos resultados, basados en la inclusión real del estado de estabilidad de microsatélites en lugar de imputado y la presencia de depósitos tumorales, confirman la precisión predictiva y la confiabilidad de la calculadora. (Traducción-Dr Osvaldo Gauto ).

Validation of the Proposed International Association for the Study of Lung Cancer Residual Tumor Classification to Upgrade Extracapsular Extension of Tumor in Nodes From R0 to Incomplete Resection.

INTRODUCTION: The International Association for the Study of Lung Cancer (IASLC) proposed a revised R classification to upstage extracapsular extension (ECE) of tumor in nodes from R0 to R1. Nevertheless, evidence to confirm this proposal is insufficient. METHODS: The study included 4061 surgical patients with NSCLC. After reclassification by IASLC-R classification, overall survival (OS) was analyzed to compare patients with ECE with those with R0, R(un), and incomplete resection (R1 and R2). The recurrence pattern of ECE was evaluated to determine whether it correlated with incomplete resection. RESULTS: Among 1136 patients with N disease, those without ECE (n = 754, 67%) had a significantly better OS than those with ECE (n = 382, 33%) (p < 0.001). This negative prognostic significance was consistent across multiple subgroups. Multivariate analysis revealed that ECE was an independent prognostic risk factor (p < 0.001). When patients with ECE were separated from the IASLC-R1 group, their OS was significantly worse than that of IASLC-R(un) patients, but comparable to that of the remaining patients in the IASLC-R1 patients when analyzing all patients and patients with N disease. Moreover, patients with ECE had an increased risk of local recurrence in the mediastinum (p < 0.001), ipsilateral lung (p = 0.031), and malignant pleural effusion or nodes (p = 0.004) but not distant recurrence including contralateral or both lungs (p = 0.268), liver (p = 0.728), brain (p = 0.252), or bone (p = 0.322). CONCLUSIONS: The prognosis of ECE patients is comparable with that of R1 patients. Moreover, their higher risk of local recurrence strongly suggests the presence of occult residual tumor cells in the surgical hemithoracic cavity. Therefore, upgrading ECE into incomplete resection is reasonable.

Imaging Characteristics Predictive of Cervical Extranodal Tumor Extension in Patients With Head and Neck Squamous Cell Carcinoma.

OBJECTIVES: The aims of the study were to determine the predictive imaging findings of extranodal extension (ENE) in metastatic cervical lymph nodes of head and neck squamous cell carcinoma and to investigate the interobserver agreement among radiologists with different experience levels. MATERIALS AND METHODS: Patients with cervical lymph node dissection and who had metastatic lymph nodes and preoperative imaging were included. Three radiologists evaluated nodal necrosis, irregular contour, gross invasion, and perinodal fat stranding. They also noted their overall impression regarding the presence of the ENE. Sensitivity, specificity, odds ratios based on logistic regression, and interobserver agreement of ENE status were calculated. RESULTS: Of 106 lymph nodes (that met inclusion criteria), 31 had radiologically determined ENE. On pathologic examination, 22 of 31 nodes were positive for ENE. The increasing number of metastatic lymph nodes was associated with the presence of the ENE ( P = 0.010). Irregular contour had the highest sensitivity (78.6%) and gross invasion had the highest specificity (96%) for the determination of the ENE. The radiologists' impression regarding the presence of the pathlogical ENE had 39.3% sensitivity and 82% specificity. Metastatic lymph nodes with a perinodal fat stranding and with the longest diameter of greater than 2 cm were found to be strong predictors of the ENE. The gross invasion demonstrated the highest κ value (0.731) among the evaluated imaging criteria. CONCLUSIONS: In the assessment of ENE, the gross invasion had the highest specificity among imaging features and showed the highest interobserver agreement. Perinodal fat stranding and the longest diameter of greater than 2 cm in a metastatic lymph node were the best predictors of the ENE.

A gradient mapping guided explainable deep neural network for extracapsular extension identification in 3D head and neck cancer computed tomography images.

BACKGROUND: Diagnosis and treatment management for head and neck squamous cell carcinoma (HNSCC) is guided by routine diagnostic head and neck computed tomography (CT) scans to identify tumor and lymph node features. The extracapsular extension (ECE) is a strong predictor of patients' survival outcomes with HNSCC. It is essential to detect the occurrence of ECE as it changes staging and treatment planning for patients. Current clinical ECE detection relies on visual identification and pathologic confirmation conducted by clinicians. However, manual annotation of the lymph node region is a required data preprocessing step in most of the current machine learning-based ECE diagnosis studies. PURPOSE: In this paper, we propose a Gradient Mapping Guided Explainable Network (GMGENet) framework to perform ECE identification automatically without requiring annotated lymph node region information. METHODS: The gradient-weighted class activation mapping (Grad-CAM) technique is applied to guide the deep learning algorithm to focus on the regions that are highly related to ECE. The proposed framework includes an extractor and a classifier. In a joint training process, informative volumes of interest (VOIs) are extracted by the extractor without labeled lymph node region information, and the classifier learns the pattern to classify the extracted VOIs into ECE positive and negative. RESULTS: In evaluation, the proposed methods are well-trained and tested using cross-validation. GMGENet achieved test accuracy and area under the curve (AUC) of 92.2% and 89.3%, respectively. GMGENetV2 achieved 90.3% accuracy and 91.7% AUC in the test. The results were compared with different existing models and further confirmed and explained by generating ECE probability heatmaps via a Grad-CAM technique. The presence or absence of ECE has been analyzed and correlated with ground truth histopathological findings. CONCLUSIONS: The proposed deep network can learn meaningful patterns to identify ECE without providing lymph node contours. The introduced ECE heatmaps will contribute to the clinical implementations of the proposed model and reveal unknown features to radiologists. The outcome of this study is expected to promote the implementation of explainable artificial intelligence-assiste ECE detection.

The diagnostic accuracy of local staging in colon cancer based on computed tomography (CT): evaluating the role of extramural venous invasion and tumour deposits.

PURPOSE: The shift from adjuvant to neoadjuvant treatment in colon cancer demands the radiological selection of patients for systemic therapy. The aim of this study was to evaluate the accuracy of the CT-based TNM stage and high-risk features, including extramural venous invasion (EMVI) and tumour deposits, in the identification of patients with histopathological advanced disease, currently considered for neoadjuvant treatment (T3-4 disease). METHODS: All consecutive patients surgically treated for non-metastatic colon cancer between January 2018 and January 2020 in a referral centre for colorectal cancer were identified retrospectively. All tumours were staged on CT according to the TNM classification system. Additionally, the presence of EMVI and tumour deposits on CT was evaluated. The histopathological TNM classification was used as reference standard. RESULTS: A total of 176 patients were included. Histopathological T3-4 colon cancer was present in 85.0% of the patients with CT-detected T3-4 disease. Histopathological T3-4 colon cancer was present in 96.4% of the patients with CT-detected T3-4 colon cancer in the presence of both CT-detected EMVI and CT-detected tumour deposits. Histopathological T0-2 colon cancer was present in 50.8% of the patients with CT-detected T0-2 disease, and in 32.4% of the patients without CT-detected EMVI and tumour deposits. CONCLUSION: The diagnostic accuracy of CT-based staging was comparable with previous studies. The presence of high-risk features on CT increased the probability of histopathological T3-4 colon cancer. However, a substantial part of the patients without CT-detected EMVI and tumour deposits was diagnosed with histopathological T3-4 disease. Hence, more accurate selection criteria are required to correctly identify patients with locally advanced disease.

Extranodal extension in head and neck squamous cell carcinoma: need for accurate pretherapeutic staging to select optimum treatment and minimize toxicity.

PURPOSE OF REVIEW: In 2017, the American Joint Committee on Cancer (AJCC) introduced the inclusion of extracapsular nodal extension (ENE) into the N staging of nonviral head and neck squamous cell carcinoma (HNSCC), while retaining the traditional N classification based on the number and sizes of metastatic nodes. The extent of ENE was further defined as microscopic ENE (ENEmi) and major ENE (ENEma) based on extent of disease beyond the nodal capsule (≤ or > 2 mm). This article reviews the evidence and progress made since these changes were introduced. RECENT FINDINGS: The 'gold standard' for evaluation ENE is histopathologic examination, the current preferred primary treatment of patients with HNSCC is by radiation-based therapy ±â€Šchemotherapy or biotherapy. The current pretreatment staging is by imaging, which needs improved reliability of radiologic rENE assessment with reporting needs to consider both sensitivity and specificity (currently computed tomography images have high-specificity but low-sensitivity). Adjuvant chemotherapy is indicated for patients with ENEma to enhance disease control, whereas for patients with ENEmi, there is a need to assess the benefit of adjuvant chemotherapy. Evidence that the presence of pENE in HPV-positive oropharyngeal carcinoma is an independent prognostic factor and should be considered for inclusion in future AJCC editions has recently emerged. SUMMARY: There remains a paucity of data on the reliability of imaging in the staging of rENE, more so the for the accurate assessment of ENEmi. Optimistic early results from use of artificial intelligence/deep learning demonstrate progress and may pave the way for better capabilities in tumor staging, treatment outcome prediction, resulting in improved survival outcomes.

Radiologic extranodal extension for nodal staging in nasopharyngeal carcinoma.

PURPOSE: Extranodal extension (ENE) has the potential to add value to the current nodal staging system (N8th) for predicting outcome in nasopharyngeal carcinoma (NPC). This study aimed to incorporate ENE, as well as cervical nodal necrosis (CNN) to the current stage N3 and evaluated their impact on outcome prediction. The findings were validated on an external cohort. METHODS & MATERIALS: Pre-treatment MRI of 750 patients from the internal cohort were retrospectively reviewed. Predictive values of six modified nodal staging systems that incorporated four patterns of ENE and two patterns of CNN to the current stage N3 for disease-free survival (DFS) were compared with that of N8th using multivariate cox-regression and concordance statistics in the internal cohort. Performance of stage N3 for predicting disease recurrence was calculated. An external cohort of 179 patients was used to validate the findings. RESULTS: Incorporation of advanced ENE, which infiltrates into adjacent muscle/skin/salivary glands outperformed the other five modifications for predicting outcomes (p < 0.01) and achieved a significantly higher c-index for 5-year DFS (0.69 vs 0.72) (p < 0.01) when compared with that of N8th staging system. By adding advanced ENE to the current N3 increased the sensitivity for predicting disease recurrence from 22.4 % to 47.1 %. The finding was validated in the external cohort (5-year DFS 0.65 vs. 0.72, p < 0.01; sensitivity of stage N3 increased from 14.0 % to 41.9 % for disease recurrence). CONCLUSION: Results from two centre cohorts confirmed that the radiological advanced ENE should be considered as a criterion for stage N3 disease in NPC.