Current American Joint Committee Research Articles

Morbidity, Prognostic Factors, and Competing Risk Nomogram for Combined Hepatocellular-Cholangiocarcinoma.

Background Combined hepatocellular-cholangiocarcinoma (CHC) is a rare and heterogeneous histological subtype of primary liver cancer, which is still poorly understood. This study aimed to describe the epidemiological and clinical features, investigate the prognostic indicators, and develop a competing risk nomogram for CHC. Methods The study cohort was taken from the Surveillance, Epidemiology, and End Results database. The annual percent change (APC) in incidence was calculated using the joinpoint regression. The nomogram was developed based on multivariate competing risk survival analyses and validated by calibration curves. Akaike information criterion, Bayesian information criterion, Harrell's C-index, and area under the receiver operating characteristic curves were obtained to compare prognostic performance. Decision curve analysis was introduced to examine the clinical value of the models. Results The overall incidence of CHC was 0.062 per 100,000 individuals in 2004 and 0.081 per 100,000 individuals in 2018, with an APC of 1.0% (P > 0.05). CHC displayed intermediate clinicopathological features of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Race, tumor size, vascular invasion, extrahepatic invasion, distant metastasis, grade, surgery, and Metavir stage were confirmed as the independent predictors of cancer-specific survival. The constructed nomogram was well calibrated, which showed better discrimination power and higher net benefits than the current American Joint Committee on Cancer staging system. Patients with liver transplantation had better survival than those with hepatectomy, especially patients within the Milan Criteria (P=0.022 and P=0.015). There was no survival difference between liver transplantation and hepatectomy in patients beyond the Milan Criteria (P=0.340). Conclusion The morbidity of CHC remained stable between 2004 and 2018. The constructed nomogram could predict the prognosis with good performance, which was meaningful to individual treatment strategies optimization. CHC patients should also be considered as potential liver transplantation recipients, especially those within the Milan Criteria, but the finding still needs more evidence to be further confirmed.

Outcomes of Living Donor Liver Transplantation in Patients With a History of Ruptured Hepatocellular Carcinoma.

Background: Liver transplantation (LT) is considered a contraindication in patients with a history of hepatocellular carcinoma (HCC) rupture because ruptured HCCs are classified as T4 in the current American Joint Committee on Cancer TNM system. This study aimed to assess living donor liver transplantation (LDLT) in these patients and elucidate the factors that may have affected their outcomes.Methods: Data of patients with a history of ruptured HCC who underwent LDLT between January 1999 and December 2019 were retrospectively reviewed.Results: Among 789 patients who underwent LDLT for HCC, five (0.64%) had a history of HCC rupture. Three patients (60%) were treated with transarterial chemoembolization (TACE) or transarterial embolization (TAE) for hemostasis, and two patients (40%) achieved spontaneous hemostasis. One of two patients who achieved spontaneous hemostasis underwent surgical resection and LT at 1 week and 6 years after the rupture, respectively. The other patient underwent LT 2 days after the rupture. Four patients (80%) survived for >5 years, while two patients (40%) experienced recurrence and succumbed during the median follow-up duration of 85.3 months (range, 12.4–182.7). The recurrence first developed at 4.3 and 17.0 months after LT; these patients were managed well using surgical resection for peritoneal seeding and TACE for intrahepatic HCC.Conclusion: LDLT can be considered a treatment method even in patients with a history of HCC rupture after full evaluation of tumor biology and risk of recurrence.

Assessment of Clinicopathological Characteristics and Development of an Individualized Prognostic Model for Patients With Hepatoid Adenocarcinoma of the Stomach

Few studies have examined the clinicopathological characteristics and prognoses of patients with hepatoid adenocarcinoma of the stomach (HAS). To explore the clinicopathological characteristics and prognoses of patients with HAS and develop a nomogram to predict overall survival (OS). This prognostic study involved a retrospective analysis of data from 315 patients who received a diagnosis of primary HAS between April 1, 2004, and December 31, 2019, at 14 centers in China. OS and prognostic factors. Patients were randomly assigned to a derivation cohort (n = 220) and a validation cohort (n = 95). A nomogram was developed based on independent prognostic factors identified through a multivariable Cox mixed-effects model. Among 315 patients with HAS (mean [SD] age, 61.9 [10.2] years; 240 men [76.2%]), 137 patients had simple HAS (defined as the presence of histologically contained hepatoid differentiation areas only), and 178 patients had mixed HAS (defined as the presence of hepatoid differentiation areas plus common adenocarcinoma areas). Patients with simple HAS had a higher median preoperative α-fetoprotein level than those with mixed HAS (195.9 ng/mL vs 48.9 ng/mL, respectively; P < .001) and a higher rate of preoperative liver metastasis (23 of 137 patients [16.8%] vs 11 of 178 patients [6.2%]; P = .003). The 3-year OS rates of patients with simple vs mixed HAS were comparable (56.0% vs 60.0%; log-rank P = .98). A multivariable Cox analysis of the derivation cohort found that the presence of perineural invasion (hazard ratio [HR], 2.13; 95% CI, 1.27-3.55; P = .009), preoperative carcinoembryonic antigen levels of 5 ng/mL or greater (HR, 1.72; 95% CI, 1.08-2.74; P = .03), and pathological node category 3b (HR, 3.72; 95% CI, 1.34-10.32; P = .01) were independent risk factors for worse OS. Based on these factors, a nomogram to predict postoperative OS was developed. The concordance indices of the nomogram (derivation cohort: 0.72 [95% CI, 0.66-0.78]; validation cohort: 0.72 [95% CI, 0.63-0.81]; whole cohort: 0.71 [95% CI, 0.66-0.76]) were higher than those derived using the American Joint Committee on Cancer's AJCC Cancer Staging Manual (8th edition) pathological tumor-node-metastasis (pTNM) staging system (derivation cohort: 0.63 [95% CI, 0.57-0.69]; validation cohort: 0.65 [95% CI, 0.56-0.75]; whole cohort: 0.64 [95% CI, 0.59-0.69]) and those derived using a clinical model that included pTNM stage and receipt of adjuvant chemotherapy (derivation cohort: 0.64 [95% CI, 0.58-0.69]; validation cohort: 0.65 [95% CI, 0.56-0.75]; whole cohort: 0.64 [95% CI, 0.59-0.69]). Based on the nomogram cutoff of 10 points, the whole cohort was divided into high-risk and low-risk groups. The 3-year OS rate of patients in the high-risk group was significantly lower than that of patients in the low-risk group (29.7% vs 75.9%, respectively; log-rank P < .001), and the 3-year prognosis of high-risk and low-risk groups could be further distinguished into pTNM stage I to II (33.3% vs 80.2%; exact log-rank P = .15), stage III (34.3% vs 71.3%; log-rank P < .001), and stage IV (15.5% vs 70.3%; log-rank P = .009). This study found that perineural invasion, preoperative carcinoembryonic antigen levels of 5 ng/mL or greater, and pathological node category 3b were independent risk factors associated with worse OS. An individualized nomogram was developed to predict OS among patients with HAS. This nomogram had good prognostic value and may be useful as a supplement to the current American Joint Committee on Cancer TNM staging system.

Construction and Validation of an Immune Cell Signature Score to Evaluate Prognosis and Therapeutic Efficacy in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy with high morbidity and mortality worldwide. Tumor immune microenvironment (TIME) plays a pivotal role in the outcome and treatment of HCC. However, the effect of immune cell signatures (ICSs) representing the characteristics of TIME on the prognosis and therapeutic benefit of HCC patients remains to be further studied.Materials and methods: In total, the gene expression profiles of 1,447 HCC patients from several databases, i.e., The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium, and Gene Expression Omnibus, were obtained and applied. Based on a comprehensive collection of marker genes, 182 ICSs were evaluated by single sample gene set enrichment analysis. Then, by performing univariate and multivariate Cox analysis and random forest modeling, four significant signatures were selected to fit an immune cell signature score (ICSscore).Results: In this study, an ICSscore-based prognostic model was constructed to stratify HCC patients into high-risk and low-risk groups in the TCGA-LIHC cohort, which was successfully validated in two independent cohorts. Moreover, the ICSscore values were found to positively correlate with the current American Joint Committee on Cancer staging system, indicating that ICSscore could act as a comparable biomarker for HCC risk stratification. In addition, when setting the four ICSs and ICSscores as features, the classifiers can significantly distinguish treatment-responding and non-responding samples in HCC. Also, in melanoma and breast cancer, the unified ICSscore could verify samples with therapeutic benefits.Conclusion: Overall, we simplified the tedious ICS to develop the ICSscore, which can be applied successfully for prognostic stratification and therapeutic evaluation in HCC. This study provides an insight into the therapeutic predictive efficacy of prognostic ICS, and a novel ICSscore was constructed to allow future expanded application.

Construction and validation of nomograms for non-metastatic Ewing sarcoma: A prognostic factor analysis based on the SEER database.

Ewing sarcoma is the second most common osseous disease in children and adolescents. It presents with a poor prognosis due to the high degree of malignancy and distant metastasis. In order to predict the disease prognosis and investigate a suitable therapeutic strategy for Ewing sarcoma, the present study aimed to describe the clinical characteristics, and to construct and validate nomograms for patients with non-metastatic Ewing sarcoma. A total of 627 cases of non-metastatic Ewing sarcoma were retrospectively collected from the Surveillance, Epidemiology, and End Results database between 2005 and 2014. Survival analysis and a machine learning model were used to identify independent prognostic variables and establish nomograms to estimate overall survival (OS) and cause-specific survival (CSS). The nomograms were bootstrap internally validated and externally validated using non-metastatic Ewing sarcoma cases from the First Affiliated Hospital of Zhengzhou University. The accuracy was also assessed by comparing with current American Joint Committee on Cancer (AJCC) staging systems. The total series consisted of 627 patients with non-metastatic Ewing sarcoma with a mean age of 20.14 years. Age, tumor extension, sex, International Classification of Diseases for Oncology, 3rd Edition histology, surgery and chemotherapy were identified as independent risk factors for OS and CSS. The aforementioned outcomes were incorporated to construct the nomograms, and the concordance indices (C-indices) for internal validation of OS and CSS prediction were 0.791 and 0.813, which were higher than those for AJCC sixth edition (OS, 0.531; CSS, 0.534) and seventh edition (OS, 0.547; CSS, 0.561), while the C-indices for external validation of OS and CSS prediction were 0.834 and 0.825, respectively. In conclusion, age, sex, tumor extension and surgery were independent prognostic factors for both OS and CSS. In addition, with regard to OS, the Ewing sarcoma subtype was a poor factor and chemotherapy was a favorable one. Nomograms based on reduced Cox models attained a satisfactory accuracy in predicting the survival of patients with non-metastatic Ewing sarcoma and could assist clinicians in evaluating survival more accurately.

Prognostic implications of extranodal extension in papillary thyroid carcinomas: A propensity score matching analysis and proposal for incorporation into current tumor, lymph node, metastasis staging

BackgroundThe current American Joint Committee on Cancer tumor, lymph node, metastasis cancer staging system for papillary thyroid carcinoma places low weight on extranodal extension. This study examined the prognostic implications of extranodal extension in papillary thyroid carcinoma patients and attempted to design a new staging system incorporating extranodal extension. MethodsWe reviewed data from 6,165 consecutive papillary thyroid carcinoma patients from 2012 to 2018. Patients with extrathyroidal extension or extranodal extension were included and then divided into 3 groups: extrathyroidal extension (papillary thyroid carcinoma with extrathyroidal extension but without extranodal extension, N = 457); extranodal extension (papillary thyroid carcinoma with extranodal extension but without extrathyroidal extension, N = 116); and extrathyroidal extension and extranodal extension (papillary thyroid carcinoma with both extrathyroidal extension and extranodal extension, N = 116). Recurrence-free survival and cancer-specific survival were compared before and after adjusting for differences using propensity score matching owing to observed heterogeneity in baseline characteristics in the original cohort. Recurrence-free survival and cancer-specific survival were also compared between patients with and without extranodal extension after matching at a 1:1 ratio. Cox proportional hazards regression analyses were used to identify the relationships of factors associated with structural recurrent disease in the node-positive subset. Then a new staging system incorporating extranodal extension was established, and the discrimination of the new staging system for recurrence-free survival and cancer-specific survival was investigated. ResultsOf the 6,165 patients with papillary thyroid carcinoma, extrathyroidal extension was found in 573 (9.3%) patients, and extranodal extension was observed in 232 (3.8%) patients. The recurrence-free survival and cancer-specific survival rates of patients with extranodal extension were similar to those of patients with extrathyroidal extension (all P > .05). Patients with extrathyroidal extension and extranodal extension experienced worse recurrence-free survival than patients with extrathyroidal extension or extranodal extension and even worse cancer-specific survival than patients with extrathyroidal extension (all P < .05). The recurrence-free survival and cancer-specific survival rates of patients with extranodal extension were worse than those of patients without extranodal extension (P = .003; P = .048). Cox proportional hazards regression analysis demonstrated that after propensity score matching, extranodal extension (hazard ratio 1.911; 95% confidence interval 1.568–3.609; P < .001) remained an independent predictor of structural recurrent disease in patients with node-positive papillary thyroid carcinoma. After incorporating extranodal extension into the current tumor, lymph node, metastasis classification, the new staging system presented a better discrimination for recurrence-free survival and cancer-specific survival for those with lymph node metastasis. ConclusionPapillary thyroid carcinoma patients with extranodal extension present worse prognosis, and incorporating extranodal extension in tumor, lymph node, metastasis classification identifies poor-risk patients more accurately.

Development and Validation of a Modified Pathologic Nodal Classification System for Cutaneous Melanoma

Given the evolving patterns of lymph node evaluation for cutaneous melanoma, it is unclear whether the current nodal classification system will continue to accurately reflect prognosis in the modern era. Existing nodal staging for cutaneous melanoma was developed primarily for patients undergoing completion lymph node dissection (CLND) for node-positive disease and does not produce groups with continuously increasing mortality. To develop and validate a modified nodal classification system for cutaneous melanoma. This retrospective cohort analysis included 105 785 patients with cutaneous melanoma undergoing surgery and nodal evaluation from January 1, 2004, to December 31, 2015, in the National Cancer Database. Extent of lymph node dissection was available for patients diagnosed in 2012 and onward. Multivariable models were generated with number of positive lymph nodes modeled using restricted cubic splines. A modified nodal classification system was derived using recursive partitioning analysis (RPA). The proposed lymph node classification system was validated in 85 499 patients from the Surveillance, Epidemiology, and End Results (SEER-18) database. Data were analyzed from April 9, 2020, to May 28, 2021. Overall survival. Among the 105 785 patients included in the analysis (62 496 men [59.1%]; mean [SD] age, 59.9 [15.5] years), number of positive lymph nodes (hazard ratio [HR] per lymph node for 0 to 2 positive lymph nodes, 2.48 [95% CI, 2.37-2-61; P < .001]; HR per lymph node for ≥3 positive lymph nodes, 1.10 [95% CI 1.07-1.13; P < .001]), clinically detected metastases (HR, 1.35; 95% CI, 1.27-1.42; P < .001), and in-transit metastases (HR, 1.48; 95% CI, 1.34-1.65; P < .001) were independently associated with mortality. An RPA-derived system using these variables demonstrated continuously increasing mortality for each proposed lymph node classification group, with HRs of 1.83 (95% CI, 1.76-1.91) for N1a, 2.72 (95% CI, 2.58-2.86) for N1b, 3.79 (95% CI, 3.51-4.08) for N2a, 4.56 (95% CI, 4.22-4.92) for N2b, 6.15 (95% CI, 5.59-6.76) for N3a, and 8.25 (95% CI, 7.64-8.91) for N3b in the proposed system (P < .001). By contrast, the current American Joint Committee on Cancer (AJCC) nodal classification system produced a more haphazard mortality profile, with HRs of 1.83 (95% CI, 1.76-1.91) for N1a, 3.81 (95% CI, 3.53-4.12) for N1b, 2.59 (95% CI, 2.30-2.93) for N1c, 2.71 (95% CI, 2.56-2.87) for N2a, 4.51 (95% CI, 4.17-4.87) for N2b, 3.44 (95% CI, 2.60-4.55) for N2c, 6.06 (95% CI, 5.51-6.67) for N3a, 8.15 (95% CI, 7.54-8.81) for N3b, and 6.90 (95% CI, 5.60-8.49) for N3c. As a sensitivity analysis, the proposed system continued to accurately stratify patients when excluding those undergoing CLND for microscopic lymph node metastases. This system was validated for overall survival and cause-specific mortality in SEER-18. Last, a new overall staging system for node-positive patients was developed by RPA and demonstrated improved concordance vs the AJCC, 8th edition system (C statistic, 0.690 [95% CI, 0.689-0.691] vs 0.666 [95% CI, 0.666-0.668]). The findings of this cohort study suggest that a modified nodal classification system can accurately stratify mortality risk in cutaneous melanoma in an era of increasing use of sentinel lymph node biopsy without CLND and should be considered for future staging systems.

Tumor primary site as a prognostic factor for Merkel cell carcinoma disease-specific death

Merkel cell carcinoma (MCC) primary site has not been fully investigated as a potential prognostic factor. To determine the incidence by tumor primary site of death due to MCC. We undertook a retrospective analysis of the Survival, Epidemiology, and End Results database. MCC patients treated between 1973 and 2016 were grouped by tumor primary site and a competing risks analysis was performed to test the impact of primary site on disease-specific death. Cumulative incidence of Merkel cell carcinoma-specific mortality (CMMI) at 5years was estimated for each primary site. Of 9407 MCC patients identified, 6305 (67.0%) had localized disease, 2397 (25.5%) had regional metastasis, and 705 (7.5%) had distant metastasis. Tumor primary site was predictive of CMMI and varied by stage at diagnosis. Tumors involving the scalp/neck carried the highest CMMI among localized MCC (26.0%). Tumors involving the lip had the highest CMMI among MCC with regional metastasis (56.7%) and distant metastasis (82.1%). Tumor size data were missing for a large proportion of patients, precluding stratification by stage according to current American Joint Committee on Cancer guidelines. Probability of MCC disease-specific death varies by primary site. The primary site of the tumor may be useful as a prognostic indicator for MCC.

Development and Validation of Nomograms to Predict Local, Regional, and Distant Recurrence in Patients With Thin (T1) Melanomas.

Although the prognosis of patients with thin primary cutaneous melanomas (T1, ≤ 1.0 mm) is generally excellent, some develop recurrence. We sought to develop and validate a model predicting recurrences in patients with thin melanomas. A Dutch population-based cohort (n = 25,930, development set) and a cohort from an Australian melanoma treatment center (n = 2,968, validation set) were analyzed (median follow-up 6.7 and 12.0 years, respectively). Multivariable Cox models were generated for local, regional, and distant recurrence-free survival (RFS). Discrimination was assessed using Harrell's C-statistic for each outcome. Each nomogram performance was evaluated using calibration plots defining low-risk and high-risk groups as the lowest and top 5% of the nomogram risk score, respectively. The nomograms' C-statistics were compared with those of a model including the current American Joint Committee on Cancer staging parameters (T-stage and sentinel node status). Local, regional, and distant recurrences were found in 209 (0.8%), 503 (1.9%), and 203 (0.8%) Dutch patients, respectively, and 23 (0.8%), 61 (2.1%), and 75 (2.5%) Australian patients, respectively. C-statistics of 0.79 (95% CI, 0.75 to 0.82) for local RFS, 0.77 (95% CI, 0.75 to 0.78) for regional RFS, and 0.80 (95% CI, 0.77 to 0.83) for distant RFS were obtained for the development model. External validation showed C-statistics of 0.80 (95% CI, 0.69 to 0.90), 0.76 (95% CI, 0.70 to 0.82), and 0.74 (95% CI, 0.69 to 0.80), respectively. Calibration plots showed a good match between predicted and observed rates. Using the nomogram, the C-statistic was increased by 9%-12% for the development cohort and by 11%-15% for the validation cohort, compared with a model including only T-stage and sentinel node status. Most patients with thin melanomas have an excellent prognosis, but some develop recurrence. The presented nomograms can accurately identify a subgroup at high risk. An online calculator is available at www.melanomarisk.org.au.

Dissecting the Lymphatic System to Predict Melanoma Metastasis

Melanoma is the most lethal form of skin cancer in the United States. Current American Joint Committee on Cancer (AJCC) staging uses Breslow depth and ulceration as the two primary tumor factors that predict metastatic risk in cutaneous melanoma. Early disease stages are generally associated with high survival rates. However, in some cases, patients with thin melanomas develop advanced disease, suggesting other factors may contribute to the metastatic potential of an individual patient’s melanoma. This review focuses on the role of the lymphatic system in the metastasis of cutaneous melanoma, from recent discoveries in mechanisms of lymphangiogenesis to elements of the lymphatic system that ultimately may aid clinicians in determining which patients are at highest risk. Ultimately, this review highlights the need to integrate pathological, morphological, and molecular characteristics of lymphatics into a “biomarker” for metastatic potential.

Duodenal, ampullary, and pancreatic neuroendocrine tumors: Oncologic outcomes are driven by tumor biology and tissue of origin.

Periampullary neuroendocrine tumors (NETs) arise from the duodenum, ampulla, and periampullary pancreas. Duodenal and ampullary NETs are rare and may have distinct biologic behavior from pancreatic NETs (P-NETs). We examined the outcomes of these entities. An institutional database was queried for patients undergoing resection for pancreatic head, duodenal, or ampullary NETs from 2000 to 2018. Patients with MEN1 syndrome or follow up less than 12 months were excluded. Three hundred and ten patients were identified. Tumor locations were ampulla (n = 15), duodenum (n = 35) and pancreas (n = 260). Median follow-up and recurrence-free survival (RFS) were 60.9 (interquartile range [IQR]: 34.8-99.3) and 171.7 (IQR: 84.0-NR) months. Clinicopathologic data and survival outcomes were similar for duodenal and ampullary NETs (RFS: p = .347 and overall survival [OS]: p = .246) and were combined into an intestinal subtype (IS) group. There were no differences in OS or RFS when comparing IS-NET and P-NET. On multivariate analysis, tissue of origin was not associated with risk of recurrence. The current American Joint Committee on Cancer staging guidelines, which account for origin tissue, were predictive of outcomes for all subtypes. Tissue of origin does not appear to impact long-term outcomes when comparing IS-NETs and P-NETs. The AJCC staging system offers good discriminatory capacity in the context of the tissue type.

The Head and Neck Oncology Specimen: The Gross Examination as an Essential Component to Diagnosis and Optimal Patient Outcomes

Abstract Achieving complete resection in head and neck oncologic cancer surgeries without leaving behind residual disease is the most significant factor to minimize the risk of locoregional recurrence and overall survival. Approaches regarding how to handle en bloc specimens for margin assessment also impact patients' long-term outcomes. Although sampling the tumor bed to evaluate for residual tumor at surgical margins (excision edges) is the most commonly practiced technique, some studies have shown that separately submitted tumor bed margins have lower sensitivity for tumor assessment compared with detection of those positive margins from direct sampling of the en bloc specimen. Close collaboration between the surgeon and pathologist is fundamental to optimize surgical margin assessment and reporting. Current American Joint Committee on Cancer (eighth edition) and National Comprehensive Cancer Network guidelines recommend the en bloc specimen sampling for intraoperative assessment of surgical margins. Cutoffs less than 5 mm between tumor and the surgical margin had been considered adequate in specific subsites in head and neck region. Emerging in situ imaging modalities and molecular testing may help to reduce inadequate surgical margins during tumor resections; however, further studies and validation are needed. This article presents a review of recent publications and guidelines of general grossing principles and recent updates to optimize cancer-free surgical margins and to emphasize the limitation issues encountered in routine practice.

A Novel Nomogram including AJCC Stages Could Better Predict Survival for NSCLC Patients Who Underwent Surgery: A Large Population-Based Study.

Objective In this study, we aimed to establish a novel nomogram model which was better than the current American Joint Committee on Cancer (AJCC) stage to predict survival for non-small-cell lung cancer (NSCLC) patients who underwent surgery. Patients and Methods. 19617 patients with initially diagnosed NSCLC were screened from Surveillance Epidemiology and End Results (SEER) database between 2010 and 2015. These patients were randomly divided into two groups including the training cohort and the validation cohort. The Cox proportional hazard model was used to analyze the influence of different variables on overall survival (OS). Then, using R software version 3.4.3, we constructed a nomogram and a risk classification system combined with some clinical parameters. We visualized the regression equation by nomogram after obtaining the regression coefficient in multivariate analysis. The concordance index (C-index) and calibration curve were used to perform the validation of nomogram. Receiver operating characteristic (ROC) curves were used to evaluate the clinical utility of the nomogram. Results Univariate and multivariate analyses demonstrated that seven factors including age, sex, stage, histology, surgery, and positive lymph nodes (all, P < 0.001) were independent predictors of OS. Among them, stage (C-index = 0.615), positive lymph nodes (C-index = 0.574), histology (C-index = 0.566), age (C-index = 0.563), and sex (C-index = 0.562) had a relatively strong ability to predict the OS. Based on these factors, we established and validated the predictive model by nomogram. The calibration curves showed good consistency between the actual OS and predicted OS. And the decision curves showed great clinical usefulness of the nomogram. Then, we built a risk classification system and divided NSCLC patients into two groups including high-risk group and low-risk group. The Kaplan–Meier curves revealed that OS in the two groups was accurately differentiated in the training cohort (P < 0.001). And then, we validated this result in the validation cohort which also showed that patients in the high-risk group had worse survival than those in the low-risk group. Conclusion The results proved that the nomogram model had better performance to predict survival for NSCLC patients who underwent surgery than AJCC stage. These tools may be helpful for clinicians to evaluate prognostic indicators of patients undergoing operation.

Novel Nomograms Individually Predicting Overall Survival of Non-metastatic Colon Cancer Patients.

Background: This study aimed to develop an effective prognostic nomogram for predicting non-metastatic colon cancer.Methods: The Surveillance, Epidemiology, and End Results program was utilized to analyze patients who underwent surgical therapy (25,350 for training, 10,860 for validation). Nomograms were created depending upon multivariate analysis in the training cohort and were compared to current American Joint Committee on Cancer (AJCC) classifications. Areas under the receiver-operating characteristic curves (AUCs), Akaike's information criterions (AICs), and calibration curves were used. The clinical benefit was measured using decision curve analyses (DCAs). The validation cohort was used to validate the results.Results: Nomogram 1 included age, gender, histological grade, T stage, number of retrieved lymph nodes, tumor size, and N stage. Nomogram 2 included age, gender, histological grade, T stage, number of retrieved lymph nodes, tumor size, and number of positive lymph nodes. The prognostic discrimination of nomogram 1 (AUC, 0.729, 95% CI, 0.723–0.736) was better than that of nomogram 2 (AUC, 0.704, 95% CI, 0.698–0.710, p < 0.001) in five-year overall survival in the training cohort. Nomogram 1 (AIC, 137,319) also showed superior model-fitting compared to nomogram 2 (AIC, 137,453). Similarity, nomogram 1 was better than the AJCC 6th and 8th TNM classifications. DCA revealed that nomogram 1 had a superior net benefit than other models. These findings were validated using the validation cohort.Conclusions: The proposed nomogram 1 was a better prognostic prediction model with better discrimination and superior model-fitting for patients with non-metastatic colon cancer, which might prove to be clinically helpful.

Prognostic significance of microscopic size in peripherally located scar-associated clinical stage I lung carcinomas

ObjectivesStaging of non-small cell lung carcinoma associated with scar is not discussed in detail in the current American Joint Committee on Cancer staging manual. The recommendation is to include the scar area in the tumor size measurement unless the tumor represents a small focus at the edge of the scar. The aim of this study is to investigate if subtraction of the size of the central scar from the total gross size of surgically resected peripheral clinical stage I non-small cell lung carcinoma improves patient stratification into more accurate prognostic groups. Materials and methodsHematoxylin and eosin sections of 148 non-small cell lung carcinomas (98 adenocarcinomas and 50 squamous cell carcinomas) were reviewed, including 44 adenocarcinomas and 9 squamous cell carcinomas with scar and 54 adenocarcinomas and 41 squamous cell carcinomas without scar. The microscopic size of the invasive tumor component was determined after the average percentage of scar tissue was subtracted from the grossly measured tumor diameter. Manual results were compared to digital image analysis. ResultsAdenocarcinoma with scar were associated with better overall (80.5 % vs. 63.2 %, p = 0.026) and cancer specific survival (95.2 % vs. 73.3 %, p = 0.0053) when compared to adenocarcinoma without scar. Better cancer specific survival was observed in acinar and papillary predominant adenocarcinoma (95.8 % with scar vs. 67.8 % without scar, p = 0.01); while similar trend although not statistically significant was observed in adenocarcinomas with solid or micropapillary component. Using microscopic size, pathologic T stage was down-staged in 21 adenocarcinomas. Squamous cell carcinoma with or without scar did not show a difference in survival. Manual and quantitative image analysis showed strong correlation (r = 0.9769, p < 0.0001). ConclusionOur study suggests that microscopic size of the invasive component in acinar and papillary predominant adenocarcinoma with scar might be a better predictor of survival than the total gross size.

Positive lymph node number and extranodal extension for predicting recurrence and survival in patients with salivary gland cancer.

This study compared our proposed N classification including the addition of the number of positive lymph node (LN+) and extranodal extension (ENE) with the current and previous American Joint Committee on Cancer (AJCC) N classifications in salivary gland cancer (SGC). This study involved 172 SGC patients who underwent surgery. Cox proportional hazard regression analyses were used to identify factors associated with overall survival (OS) and disease-free survival (DFS). In multivariate analyses, LN+ number, LN ratio, and ENE were associated with OS and DFS outcomes (all P < .05). Our new N classification proposed three categories: N0 (0 LN+), N1 (1 LN+), and N2 (≥2 LN+ or ENE). The C-index of our N classification showed improvement in OS prediction (0.768) compared with the AJCC seventh (0.743) and eighth (0.756) edition N classifications. Our proposed N classification incorporating LN+ number and ENE may improve prediction of post-treatment survival and recurrence in patients with SGC.

Prognostic classification for patients with nasopharyngeal carcinoma based on American Joint Committee on cancer staging system T and N categories

Background: This study examined the current American Joint Committee on Cancer (AJCC) 8th edition staging system and proposes a new classification for nasopharyngeal carcinoma (NPC).

Older patients with differentiated thyroid cancer exhibit more aggressive pathological characteristics than younger patients

Differentiated thyroid cancer (DTC) has long been recognized as having a worse prognosis in older people. We retrospectively evaluated the clinical and pathological characteristics of 973 sequentially treated patients with primary DTC stratified into 2 age groups, ≥ 55 or < 55 years, based on the current American Joint Committee on Cancer (AJCC) DTC staging system. We found that older patients had a higher frequency of extrathyroidal cancer extension and larger cancers, and that their cancers were less commonly completely resectable.

Microvascular Invasion and a Size Cutoff Value of 2 cm Predict Long-Term Oncological Outcome in Multiple Hepatocellular Carcinoma: Reappraisal of the American Joint Committee on Cancer Staging System and Validation Using the Surveillance, Epidemiology, and End-Results Database

Introduction: For prognostication of hepatocellular carcinoma (HCC), the optimal size cutoff value and the significance of microvascular invasion (mvi) remain inconclusive. Objective: This study sought to revisit the inconclusive components of current American Joint Committee on Cancer (AJCC) staging system and to develop a new practical prognostication model for patients with HCC based on 2 large cohorts. Method: In 1,175 patients who underwent resection for HCC (training cohort), prognostic significance of mvi, and optimal size cutoff value were revisited and a new staging model was established. Then, its performance was validated using 5,249 patients derived from a population-based database (validation cohort). Results: The optimal size cutoff value was 2 cm in multiple HCC, similar to that for solitary HCC. Multivariate analyses confirmed that mvi, a size >2 cm, and multiple lesions were independent predictors with similar weights for disease-specific survival. Based on these results, earlier stages of HCC were reclassified according to the number of the following factors: multiple tumors, >2 cm in diameter, and presence of mvi. Also, given the similar prognosis of Stages IIIB and IVA according to the AJCC 8th edition, these groups were reclassified into the same stage. This new staging model had a better performance than the AJCC 8th edition in both training cohort (c-statistics, 0.648 vs. 0.629) and the validation cohort (c-statistics, 0.646 vs. 0.645) regardless of the presence of cirrhosis. Conclusions: Inclusion of a size cutoff value of 2 cm and mvi could reclassify the current version of the AJCC staging system and offer an alternative prognostication model using a single size-cutoff value of HCC.

Low-Grade Appendiceal Mucinous Neoplasms: A Single Institution Experience of 64 Cases With Clinical Follow-up and Correlation With the Current (Eighth Edition) AJCC Staging.

Background. In this single-institution study, we applied the current (eighth edition) American Joint Committee on Cancer pathologic staging criteria to 64 low-grade mucinous neoplasms of the appendix (LAMNs), examined their histopathologic features, and studied the patients' clinical outcomes. Design. Sixty-four LAMNs, with a median follow-up of 52 months, were reviewed. Results. The distribution of pathologic stages was pTis (n = 39), pT3 (n = 1), pT4a (n = 5), pT4aM1a (n = 8), and pT4aM1b (n = 11). Recurrence was observed in only 2 patients (both with pT4aM1b disease), one of whom died of disease. All remaining patients were disease-free after a median clinical follow-up of 60 months. Conclusions. Our study confirms that pTis LAMNs have an excellent prognosis and suggests that pT4a and pT4aM1a LAMNs may also have a low risk of developing progressive disease.