Showing papers on "AJCC staging system published in 2021"

Nomogram Based on Lactate Dehydrogenase-to-Albumin Ratio (LAR) and Platelet-to-Lymphocyte Ratio (PLR) for Predicting Survival in Nasopharyngeal Carcinoma

Abstract: Purpose The prognosis of inflammation-related indicators like lactate dehydrogenase/albumin ratio (LAR) and the platelet/lymphocyte ratio (PLR) in nasopharyngeal carcinoma (NPC) is not yet clear. Our objective is to establish and verify the nomogram using LAR and PLR ratio for the first time to explore the prognostic value in NPC. Patients and methods This was a retrospective collection of 1661 patients with non-metastatic NPC admitted to our hospital from 2010 to 2017. The final variables of overall survival (OS) and progression-free survival (PFS) were selected by Cox regression analysis to establish nomograms, and the methods to verify the prediction precision and discriminative ability of the nomograms were concordance index (C index), the receiver operating characteristic (ROC) curve and calibration curve. The risk stratification was carried out through the nomograms and compared with the current staging system by the Kaplan-Meier methods. Results Multivariate Cox analysis resulted that age, plasma Epstein-Barr Virus (EBV) DNA, T stage, N stage, white blood cells (WBC), PLR and LAR were independent prognostic risk factors for OS and PFS, and sex is an independent prognostic risk factor for OS. The C-indexes of OS nomogram were 0.722 (95% CI: 0.706-0.738) and 0.747 (95% CI: 0.717-0.777) in the training cohort and validation cohort, which were statistically higher than the current 8th AJCC staging system (0.646 and 0.688). The C-indexes of PFS nomogram were 0.696 (95% CI: 0.680-0.713) and 0.690 (95% CI: 0.660-0.720), which were also statistically higher than the current 8th AJCC staging system (0.632 and 0.666). Otherwise, ROC curves and the calibration curve for probability also confirmed satisfied consistency with actual observations. Conclusion LAR is a novel useful independent factor in NPC. The proposed nomogram LAR and PLR resulted in more accurate prognostic prediction than current staging system for NPC patients.

Development and validation of prognostic nomograms for early-onset locally advanced colon cancer.

Abstract: Background The incidence of colorectal cancer in patients younger than 50 years has been increasing in recent years. Objective Develop and validate prognostic nomograms predicting overall survival (OS) and cancer-specific survival (CSS) for early-onset locally advanced colon cancer (EOLACC) based on the Surveillance, Epidemiology, and End Results (SEER) database. Results The entire cohort comprised 13,755 patients with EOLACC. The nomogram predicting OS for EOLACC displayed that T stage contributed the most to prognosis, followed by N stage, regional nodes examined (RNE) and surgery. The nomogram predicting CSS for EOLACC demonstrated similar results. Various methods identified the discriminating superiority of the nomograms. X-tile software was used to classify patients into high-risk, medium-risk, and low-risk according to the risk score of the nomograms. The risk stratification effectively avoided the survival paradox. Conclusions We established and validated nomograms for predicting OS and CSS based on a national cohort of almost 13,000 EOLACC patients. The nomograms could effectively solve the issue of survival paradox of the AJCC staging system and be an excellent tool to integrate the clinical characteristics to guide the therapeutic choice for EOLACC patients. Methods Nomograms were constructed based on the SEER database and the Cox regression model.

Grading Solid Pseudopapillary Tumors of the Pancreas: the Fudan Prognostic Index

Abstract: Ki-67 has been shown to predict outcome of patients with solid pseudopapillary tumor of the pancreas (SPTP) but has not been incorporated into a formal classification system to predict recurrence-free survival (RFS). This is a retrospective cohort study of patients with histologically confirmed diagnosis of SPTP who had at least 1 year of follow-up at two tertiary academic centers. Survival data were assessed by Kaplan–Meier method and multivariable Cox regression model. Prognostic performance was compared among various systems. A total of 193 consecutive patients were included, ranging in age from 12 to 70 years (median 33 years). Seven patients (3.6%) developed tumor recurrence. The 3-, 5-, and 10-year RFS rates were estimated at 96.9%, 96.1%, and 94.8%, respectively. For the AJCC staging system, patients with stage I had similar prognosis to those with stage II. For the ENETS staging system, patients with stage I to III had similar prognosis. Grade based on Ki-67 was superior to both the AJCC and ENETS systems for predicting survival. Multivariate analysis revealed that large tumor size [> 10 cm; hazard ratio (HR), 6.177 95% confidence interval (CI), 1.289–29.603; P = 0.023] and Ki-67 (HR, 17.199 95% CI, 4.001–73.930; P < 0.001) were independent predictors for RFS. The Fudan Prognostic Index based on the combination of Ki-67 and tumor size showed excellent discrimination for RFS and was more accurate and informative than other grading/staging systems. The Fudan Prognostic Index better predicts RFS compared with either Ki-67 alone or the current AJCC and ENETS TNM-based staging systems.

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

Abstract: Background 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. Methods 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. Results 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. Conclusion 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.

Development and validation of a new clinical staging system to predict survival for esophageal squamous cell carcinoma patients: Application of the nomogram.

Abstract: Introduction Survival of patients with the same clinical stage varies widely and effective tools to evaluate the prognosis utilizing clinical staging information is lacking. This study aimed to develop a clinical nomogram for predicting survival of patients with Esophageal Squamous Cell Carcinoma (ESCC). Materials and methods On the basis of data extracted from the SEER database (training cohort, n = 3375), we identified and integrated significant prognostic factors for nomogram development and internal validation. The model was then subjected to external validation with a separate dataset obtained from Jinling Hospital of Nanjing Medical University (validation cohort, n = 1187). The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index), Akaike information criterion (AIC) and calibration curves. And risk group stratification was performed basing on the nomogram scores. Results On multivariable analysis of the training cohort, seven independent prognostic factors were identified and included into the nomogram. Calibration curves presented good consistency between the nomogram prediction and actual observation for 1-, 3-, and 5-year OS. The AIC value of the nomogram was lower than that of the 8th edition American Joint Committee on Cancer TNM (AJCC) staging system, whereas the C-index of the nomogram was significantly higher than that of the AJCC staging system. The risk groups stratified by CART allowed significant distinction between survival curves within respective clinical TNM categories. Conclusions The risk stratification system presented better discriminative ability for survival prediction than current clinical staging system and might help clinicians in decision making.

Serum Extracellular Vesicle-Derived miRNAs in Patients with Non-Small Cell Lung Cancer—Search for Non-Invasive Diagnostic Biomarkers

Abstract: The aim of the study was a search for diagnostic and/or prognostic biomarkers in patients with non-small cell lung cancer (NSCLC) patients, based on circulating microRNAs (miRs: miR-23a, miR-361, miR-1228 and miR-let7i) in extracellular vesicles (EVs). Serum EVs were isolated from NSCLC patients (n = 31) and control subjects (n = 21). RNA was isolated from EVs and reverse transcription reaction was performed. Relative levels of miR-23a, miR-361, miR-1228 and miR-let7i were assessed in real-time qPCR using TaqMan probes. Analysis was based on the 2-ΔΔCT method. Statistically significant lower levels of miR-23a and miR-let7i were observed among NSCLC patients vs. control group: miR-23a, 0.054 vs. 0.107; miR-let7i, 0.193 vs. 0.369 (p = 0.003, p = 0.005, respectively). A receiver operating characteristic (ROC) curve analysis demonstrated the diagnostic potential of each individual serum EV-derived miRNA with an area under the curve AUC = 0.744 for miR-23a (p = 0.0003), 0.733 for miR-let7i (p = 0.0007). The decreased level of miR-23a in patients correlated with metastasis to lymph nodes and with AJCC tumor staging system. The results demonstrate that miR-23a and miR-let7i may prove clinically useful as significant, non-invasive markers in NSCLC diagnosis. Additionally, changing profile level of miR-23a that correlates with cancer development may be considered as an NSCLC progression marker.

Proposed modification of the eighth edition of the AJCC staging system for intrahepatic cholangiocarcinoma.

Abstract: Background To improve the prognostic accuracy of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system for intrahepatic cholangiocarcinoma (ICC) with establishment and validation of a modified TNM (mTNM) staging system. Methods Data on patients who underwent curative-intent resection for ICC was collected from 15 high-volume centers worldwide (n = 643). An external validation dataset was obtained from the SEER registry (n = 797). The mTNM staging system was proposed by redefining T categories, and incorporating the recently proposed N status as N0 (no lymph node metastasis [LNM]), N1 (1–2 LNM) and N2 (≥3 LNM). Results The 8th AJCC TNM staging system failed to stratify overall survival (OS) of stage II versus IIIA, stage IIIB versus IV, as well as overall stage III versus IV among all patients from the two databases, as well as stage I versus II, and stage III versus III among patients who had ≥6 LNs examined. There was a monotonic decrement in survival based on the proposed mTNM staging classification among patients derived from both the multi-institutional (Median OS, stage I 69.8 vs. II 37.1 vs. III 18.9 vs. IV 16.4 months, all p Conclusion The modified TNM staging system for ICC using the new T and N definitions provided an improved means to stratify patients relative to long-term OS versus the 8th AJCC staging.

Negative Prognostic Implication of TERT Promoter Mutations in Human Papillomavirus–Negative Tonsillar Squamous Cell Carcinoma Under the New 8th AJCC Staging System

Abstract: Telomerase reverse transcriptase gene promoter (TERTp) mutation is a potential candidate for pathogenesis and therapeutic target of tonsillar squamous cell carcinomas (TSCCs) in association with human papillomavirus (HPV). Their clinical relevance has not been validated under the new 8th American Joint Committee on Cancer (AJCC) staging system. We analyzed real-time peptide nucleic acid-mediated PCR and sequencing methods (TERTp mutation) and real-time PCR-based assay (HPV) in 80 surgically resected TSCCs. The 8th edition staging system improved the stratification of the early and advanced stages and between T or N categories for overall survival over the 7th edition. TERTp mutation was found in 7.5%, and HPV in 80.0% of the patients. The majority (83.3%) of TERTp mutation cases were HPV-positive TSCCs. Applying the 8th edition staging system, TERTp mutation was an independent factor of poor prognosis for disease-free survival (DFS) in TSCC patients, supporting the clinical significance of TERTp mutation in tonsil cancer. TERTp mutations were also negatively correlated with overall survival and DFS in HPV-negative TSCCs. Conclusively, TERTp mutation provides negative prognostic impact on survival of surgically managed tonsil cancers staged with the AJCC 8th edition.

Tumor Size Still Impacts Prognosis in Breast Cancer With Extensive Nodal Involvement.

Abstract: Background and Purpose Although tumor size and nodal status are the most important prognostic factors, it is believed that nodal status outperforms tumor size as a prognostic factor. In particular, when patients have a nodal stage greater than N2 (more than nine positive lymph nodes), it is well accepted that tumor size does not retain its prognostic value. Even in the newest American Joint Committee on Cancer (AJCC) prognostic staging system, which includes molecular subtype as an important prognostic factor, T1-3N2 patients are categorized as the same population. The same is true for T1-4N3 patients. Moreover, some physicians have speculated that for tumors staged N2 or greater, the smaller the tumor is, the more aggressive the tumor. Thus, this study aims to investigate the prognostic value of tumor stage (T stage) in patients with extensive nodal involvement and to compare the survival of T4N × M0 and T × N3M0. Patients and Methods Female breast cancer patients with nine or more positive lymph nodes or with T4 tumors were identified in the SEER registry between 2010 and 2015. The effect of T stage on breast cancer-specific survival (BCSS) was assessed using the Kaplan-Meier survival curve method and risk-adjusted Cox proportional hazard regression modeling. Survival comparison of T4NxM0 and TxN3M0 patients was also achieved using the Kaplan-Meier survival curve method and risk-adjusted Cox proportional hazard regression model. Results Overall, 21,696 women with N2-3 tumors were included from 284,073 patients.T stage, nodal stage (N stage), ER, PR, HER2 and grade were all independent prognostic factors (p <0.001). HRs for ER, PR, HER2, grade, and N stage were 0.662 (0.595-0.738), 0.488 (0.438-0.543), 0.541 (0.489-0.598), 1.534 (1.293-1.418) and 1.551 (1.435-1.676), respectively. Notably, HER2 positivity was correlated with better BCSS possibly due to the wide adoption of anti-HER2 therapy. Using T1 as a reference, HRs of T2, T3, and T4 were 1.363 (1.200-1.548), 2.092 (1.824-2.399) and 3.497 (3.045-4.017), respectively. The same results held true when subgroup analysis based on N stage were conducted. In the two subgroups, namely, women staged as T1-3N2 and women staged as T1-4N3, T stage was also a significant negative prognostic factor independent of ER, PR, HER2 and grade. Moreover, 8,328 women staged as T4 with different nodal statuses were also identified from the whole database. When we compared T4Nx with TxN3, it was found that T4 tumors exhibited worse outcomes than N3 tumors independent of other prognostic factors. When molecular subtype was included in the subgroup analysis, survival could not be distinguished between T4 and N3 only in TNBC. Conclusions In patients with extensive nodal status, tumor stage remains a prognostic factor independent of other factors, such as ER, PR, HER2, and grade. In patients with T4Nx or TxN3 tumors, T4 tumors exhibit worse outcomes than N3 tumors independent of other prognostic factors. The AJCC staging system should be modified based on these findings.

Prognostic Value of Tumor Staging: Predicting Nodal Metastases in Cutaneous Squamous Cell Carcinoma.

Abstract: OBJECTIVES Determine the ability of three staging systems to stratify the risk of nodal metastases in cases of cutaneous squamous cell carcinoma (cSCC). Examine differential staging of tumors across the three systems and the resulting implications for clinical decision making. STUDY DESIGN Retrospective chart review. METHODS This study included 118 patients who underwent excision of primary cSCC of the head and neck as well as elective neck dissection for the same tumor between 2006 and 2017. Tumors were staged using the 2010 7th edition American Joint Committee on Cancer (AJCC 7) staging system, the 2016 8th edition AJCC staging system (AJCC 8), and the Brigham and Women's Hospital (BWH) alternative tumor staging system published in 2013. RESULTS There were 28 patients (23.7%) with positive nodal metastases at the time of tumor excision. Almost all tumors staged as tumor (T)2 using AJCC 7 were upstaged to T3 or T4 using the new AJCC 8, and these two groups accounted for the majority of the nodal metastases. Similarly, the BWH-staged T3 group contained the highest number of tumors with nodal metastases. None of the three staging systems significantly stratified tumors in a manner that predicted the presence of nodal metastases. CONCLUSION Individuals with cSCC tumors staged T3 or higher in the AJCC 8 and BWH staging systems should undergo neck dissection, whereas those with lower staging should be discussed with the patient on a case-by-case basis. LEVEL OF EVIDENCE 4.

Evaluation of the AJCC Eighth-Edition Prognostic Staging System for Breast Cancer in a Latin American Cohort.

Abstract: The staging of breast cancer has been based on tumor size, lymph node involvement, and presence or absence of distant metastases. The American Joint Committee on Cancer (AJCC) staging system in its eighth edition incorporates hormone receptors, human epidermal growth factor receptor 2 (HER2), and histologic grade due to their prognostic importance. In Latin America, however, the impact of the new edition is unknown. This article evaluates the performance of the AJCC eighth-edition staging system in a cohort of patients with breast cancer at a reference center in Colombia. The study investigated a descriptive cohort of 912 patients who received complete treatment for non-metastatic invasive breast cancer and had information on the anatomic stage and biologic factors,. All the patients were restaged using the AJCC eighth-edition classification. Changes in clinical stages and differences between the two classifications were compared. The study enrolled 912 patients. Changes in staging occurred for 54.82% (downstaging for 40.3% and upstaging for 14.47%) of these patients. For recurrence-free survival, the C-Index of the eighth-edition AJCC was 0.726, and the AIC was 1323.7, whereas the C-Index of the seventh-edition AJCC was 0.731, and the AIC was 1314.3 (p = 0.99). The seventh and eighth editions of the AJCC staging system have similar predictive values in our population for recurrence-free survival. Future studies are necessary to evaluate the performance of the AJCC eighth-edition staging system in predicting overall survival.

Impact of surgical margin width on long-term outcomes for intrahepatic cholangiocarcinoma: a multicenter study

Abstract: BACKGROUND The objective of this study was to investigate the survival outcomes of surgical margin width in intrahepatic cholangiocarcinoma (ICC). METHODS Between November 2011 and August 2017, patients who underwent hepatectomy for ICC were collected from 13 major hepatopancreatobiliary centers in China. The survival outcomes for patients who underwent wide margin hepatectomy (WMH) were compared with those who underwent narrow margin hepatectomy (NMH) using the 1:1 propensity score matching (PSM). RESULTS Among 478 included patients, 195 (40.8%) underwent WMH whereas 283 (59.2%) underwent NMH. PSM yielded 79 matched patients with similar baseline characteristics. Patients underwent WMH had a significant better OS and DFS compared with those underwent NMH (before PSM: median OS 27 vs 17 months, P < 0.05; median DFS 15 vs 8 months, P = 0.001, after PSM: median OS 41 vs 22 months, p < 0.05; median DFS 16 vs 10 months, p < 0.05). However, subgroup analysis based on the AJCC staging system, WMH could only improve the survival outcomes in AJCC I ICC patients (Stage I: OS, DFS, P<0.05). CONCLUSIONS Surgeons should strive to achieve a wide surgical margin for patients with AJCC I ICC to optimize the long-term outcome.

Development and Assessment of a Clinical Calculator for Estimating the Likelihood of Recurrence and Survival Among Patients With Locally Advanced Rectal Cancer Treated With Chemotherapy, Radiotherapy, and Surgery.

Abstract: Importance Predicting outcomes in patients receiving neoadjuvant therapy for rectal cancer is challenging because of tumor downstaging. Validated clinical calculators that can estimate recurrence-free survival (RFS) and overall survival (OS) among patients with rectal cancer who have received multimodal therapy are needed. Objective To develop and validate clinical calculators providing estimates of rectal cancer recurrence and survival that are better for individualized decision-making than the American Joint Committee on Cancer (AJCC) staging system or the neoadjuvant rectal (NAR) score. Design, setting, and participants This prognostic study developed risk models, graphically represented as nomograms, for patients with incomplete pathological response using Cox proportional hazards and multivariable regression analyses with restricted cubic splines. Because patients with complete pathological response to neoadjuvant therapy had uniformly favorable outcomes, their predictions were obtained separately. The study included 1400 patients with stage II or III rectal cancer who received treatment with chemotherapy, radiotherapy, and surgery at 2 comprehensive cancer centers (Memorial Sloan Kettering [MSK] Cancer Center and Siteman Cancer Center [SCC]) between January 1, 1998, and December 31, 2017. Patients from the MSK cohort received chemoradiation, surgery, and adjuvant chemotherapy from January 1, 1998, to December 31, 2014; these patients were randomly assigned to either a model training group or an internal validation group. Models were externally validated using data from the SCC cohort, who received either chemoradiation, surgery, and adjuvant chemotherapy (chemoradiotherapy group) or short-course radiotherapy, consolidation chemotherapy, and surgery (total neoadjuvant therapy with short-course radiotherapy group) from January 1, 2009, to December 31, 2017. Data were analyzed from March 1, 2020, to January 10, 2021. Exposures Chemotherapy, radiotherapy, chemoradiotherapy, and surgery. Main outcomes and measures Recurrence-free survival and OS were the outcome measures, and the discriminatory performance of the clinical calculators was measured with concordance index and calibration plots. The ability of the clinical calculators to predict RFS and OS was compared with that of the AJCC staging system and the NAR score. The models for RFS and OS among patients with incomplete pathological response included postoperative pathological tumor category, number of positive lymph nodes, tumor distance from anal verge, and large- and small-vessel venous and perineural invasion; age was included in the risk model for OS. The final clinical calculators provided RFS and OS estimates derived from Kaplan-Meier curves for patients with complete pathological response and from risk models for patients with incomplete pathological response. Results Among 1400 total patients with locally advanced rectal cancer, the median age was 57.8 years (range, 18.0-91.9 years), and 863 patients (61.6%) were male, with tumors at a median distance of 6.7 cm (range, 0-15.0 cm) from the anal verge. The MSK cohort comprised 1069 patients; of those, 710 were assigned to the model training group and 359 were assigned to the internal validation group. The SCC cohort comprised 331 patients; of those, 200 were assigned to the chemoradiotherapy group and 131 were assigned to the total neoadjuvant therapy with short-course radiotherapy group. The concordance indices in the MSK validation data set were 0.70 (95% CI, 0.65-0.76) for RFS and 0.73 (95% CI, 0.65-0.80) for OS. In the external SCC data set, the concordance indices in the chemoradiotherapy group were 0.71 (95% CI, 0.62-0.81) for RFS and 0.72 (95% CI, 0.59-0.85) for OS; the concordance indices in the total neoadjuvant therapy with short-course radiotherapy group were 0.62 (95% CI, 0.49-0.75) for RFS and 0.67 (95% CI, 0.46-0.84) for OS. Calibration plots confirmed good agreement between predicted and observed events. These results compared favorably with predictions based on the AJCC staging system (concordance indices for MSK validation: RFS = 0.69 [95% CI, 0.64-0.74]; OS = 0.67 [95% CI, 0.58-0.75]) and the NAR score (concordance indices for MSK validation: RFS = 0.56 [95% CI, 0.50-0.63]; OS = 0.56 [95% CI, 0.46-0.66]). Furthermore, the clinical calculators provided more individualized outcome estimates compared with the categorical schemas (eg, estimated RFS for patients with AJCC stage IIIB disease ranged from 7% to 68%). Conclusions and relevance In this prognostic study, clinical calculators were developed and validated; these calculators provided more individualized estimates of the likelihood of RFS and OS than the AJCC staging system or the NAR score among patients with rectal cancer who received multimodal treatment. The calculators were easy to use and applicable to both short- and long-course radiotherapy regimens, and they may be used to inform surveillance strategies and facilitate future clinical trials and statistical power calculations.

Development and Validation of a Prognostic Nomogram for Gastric Signet Ring Cell Carcinoma: A Multicenter Population-Based Study.

Abstract: Background Gastric signet ring cell carcinoma (GSRCC) is a rare disease associated with poor prognosis. A prognostic nomogram was developed and validated in this study to assess GSRCC patients' overall survival (OS). Methods Patients diagnosed with GSRCC from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2016) and the First Hospital of China Medical University (CMU1h) were enrolled in this retrospective cohort study. Univariate and multivariate COX analysis was used to determine independent prognostic factors to construct the prognostic nomogram. Predictions were evaluated by the C-index and calibration curve. In addition, the receiver operating characteristic (ROC) curve, decision curve analysis (DCA), and Kaplan-Meier analysis were employed to assess the clinical utility of the survival prediction model. Results Patients were classified into two cohorts. We randomly divided patients in the SEER database and CMU1h cohort into a training group (n=3068, 80%) and a validation group (n=764, 20%). Age, race, T stage, N stage, M stage, therapy, and tumor size were significantly associated with the prognosis of GSRCC patients. On this basis, a nomogram was constructed, with a C-index in the training and the validation cohorts at 0.772 (95% CI: 0.762-0.782) and 0.774 (95% CI: 0.752-0.796), respectively. The accuracy of the generated nomogram was verified through calibration plots. Similarly, compared with the traditional AJCC staging system, the results of the area under curve (AUC) calculated by ROC, DCA, and Kaplan-Meier curves, demonstrated a good predictive value of the constructed nomogram, compared to the traditional AJCC staging system. Conclusion In the present study, seven independent prognostic factors of GSRCC were screened out. The established nomogram models based on seven variables provided a visualization of each prognostic factor's risk and assisted clinicians in predicting the 1-, 3-, and 5-year OS of GSRCC.

Which Staging System Is More Suitable for Gastric Neuroendocrine Cancer and Mixed Adenoneuroendocrine Carcinomas? A Multicenter Cohort Study.

Abstract: Purpose To evaluate whether the European Neuroendocrine Tumor Society (ENETS) system or the 8th American Joint Committee on Cancer (AJCC) staging manual are suitable for gastric neuroendocrine carcinomas and/or mixed adenoneuroendocrine carcinomas (G-NECs/MANECs). Methods Patients in the a multicentric series with G-NEC/MANEC who underwent curative-intent surgical resection for a primary tumor were included. An optimal staging system was proposed base on analysis of the T and N status and validated by the SEER database. Results Compared with the ENETS system, the survival curves of the T category and N category in the 8th AJCC system were better separated and distributed in a more balanced way, but the survival curves of T2 vs T3, N0 vs N1, and N3a vs N3b overlapped. For the T category, the 8th AJCC T category was modified by combining T2 and T3, which was consistent with the T category in the 6th AJCC manual for GC. For the N category, the optimal cut-off values of metastatic lymph nodes using X-tile were also similar to those of the N category in the 6th AJCC system. The Kaplan-Meier plots of the 6th AJCC system showed statistically significant differences between individual substages. Compared with the other two classifications, the 6th AJCC system also showed superior prognostic stratification. Similar results were obtained in both multicentric and SEER validation sets. Conclusions Compared to the 8th AJCC and ENETS systems, the 6th AJCC staging system for GC is more suitable for G-NEC/MANEC and can be adopted in clinical practice.

Development and validation of a nomogram to predict cancer-specific survival of uveal melanoma.

Abstract: Uveal melanoma (UM) is a rare but aggressive cancer, which is the most common primary intraocular malignancy in adults. We aimed to develop and validate a competing risk nomogram to predict cancer-specific survival (CSS) of patients with UM, as well as compare its prognostic value with that of the American Joint Committee on Cancer (AJCC) staging system. Data of patients diagnosed with UM from 2010 to 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. We extracted and integrated significant prognostic factors based on competing risk regression to build a nomogram. The nomogram with an online prediction version was also created. The performance of the nomogram was evaluated using Harrell’s concordance index (C-index) and calibration plots. Receiver operating characteristic (ROC) curve was carried out to estimate clinical applicability of the model. Improvements in the predictive accuracy of our new model compared with AJCC staging system were estimated by calculating the relative integrated discrimination improvement (IDI) and the net reclassification improvement (NRI). A total of 839 eligible patients with primary UM were randomly assigned to a training cohort (588, 70%) and a validation cohort (251, 30%). Age, histological type, T stage and M stage were independent prognostic factors to predict CSS of UM and were incorporated in the nomogram. The calibration plots indicated that the 3- and 5-year CSS probabilities were consistent between the nomogram prediction and the actual observation. The C-index for this model was 0.778 (95% CI:0.756–0.800) and 0.786 (95% CI: 0.749–0.816) in the training cohort and validation cohort. Areas under the curve (AUCs) were 0.814, 0.771, and 0.792 in the training cohort, 0.788, 0.781 and 0.804 in the validation cohort, respectively. The NRI value in AJCC staging system was − 0.153 (95% CI -0.29 – − 0.041) for 3 years of follow-up and − 0.276 (95% CI -0.415 – − 0.132) for 5 years of follow-up. The IDI values for 3 and 5 years of follow-up in the AJCC staging system were − 0.021 (P = 0.076) and − 0.045 (P = 0.004), respectively. We have developed and validated a competing risk nomogram to reliably predict cancer-specific survival of patients with UM. This convenient tool may be useful for evaluating cancer-specific prognosis.

A nomogram predicting overall survival in patients with non-metastatic pancreatic head adenocarcinoma after surgery: a population-based study

Abstract: Pancreatic head adenocarcinoma (PHAC), a malignant tumour, has a very poor prognosis, and the existing prognostic tools lack good predictive power. This study aimed to develop a better nomogram to predict overall survival after resection of non-metastatic PHAC. Patients with non-metastatic PHAC were collected from the Surveillance, Epidemiology, and End Results (SEER) database and divided randomly into training and validation cohorts at a ratio of 7:3. Cox regression analysis was used to screen prognostic factors and construct the nomogram. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated to evaluate the performance of the model. The predictive accuracy and clinical benefits of the nomogram were validated using the area under the curve (AUC), calibration curves, and decision curve analysis (DCA). From 2010 to 2016, 6419 patients with non-metastatic PHAC who underwent surgery were collected from the SEER database. A model including T stage, N stage, grade, radiotherapy, and chemotherapy was constructed. The concordance index of the nomogram was 0.676, and the AUCs of the model assessing survival at multiple timepoints within 60 months were significantly higher than those of the American Joint Committee on Cancer (AJCC) 8th staging system in the training cohort. Calibration curves showed that the nomogram had ability to predict the actual survival. The NRI, IDI, and DCA curves also indicated that our nomogram had higher predictive capability and clinical utility than the AJCC staging system. Our nomogram has an ability to predict overall survival after resection of non-metastatic PHAC and includes prognostic factors that are easy to obtain in clinical practice. It would help assist clinicians to conduct personalized medicine.

Expanding Criteria for Prognostic Stage IA in Hormone Receptor-Positive Breast Cancer

Abstract: BACKGROUND The prognostic significance of patients with low-risk Recurrence Score (RS) results in the context of the American Joint Committee on Cancer (AJCC) 8th-edition pathologic prognostic staging has not been investigated. We evaluated if expanded RS criteria can be considered for downstaging in AJCC pathologic prognostic staging. METHODS Using Surveillance, Epidemiology, and End Results data we identified patients with T1-3N0-3M0 HR-positive/HER2-negative breast cancer treated from 2010-2015 with follow-up data through 2016. We evaluated TNM categories, grade, and RS result. The primary outcome measured was 5-year disease-specific survival (DSS) of patients with low-risk RS results not already pathologic prognostic stage IA, determined by T and N categories per AJCC 8th edition. All statistical tests were 2-sided. RESULTS Of 154,050 patients with median follow-up of 49 months (range = 0-83), RS results were obtained in 60,886 (39.5%): RS was .05). For those with RS 18-25, there was a small decrease in DSS for T2N0 (2.3%) and modest decrease for T1-2N1 (4.2%-6.4%) compared to pathologic prognostic stage IA patients (P < .001). CONCLUSION Patients with RS < 18 have excellent 5-year DSS regardless of T category for N0-1 disease suggesting further modification of the AJCC staging system using this cutoff.

Prognostic Value of Combing Primary Tumor and Nodal Glycolytic-Volumetric Parameters of 18F-FDG PET in Patients with Non-Small Cell Lung Cancer and Regional Lymph Node Metastasis.

Abstract: We investigated whether the combination of primary tumor and nodal 18F-FDG PET parameters predict survival outcomes in patients with nodal metastatic non-small cell lung cancer (NSCLC) without distant metastasis. We retrospectively extracted pre-treatment 18F-FDG PET parameters from 89 nodal-positive NSCLC patients (stage IIB-IIIC). The Cox proportional hazard model was used to identify independent prognosticators of overall survival (OS) and progression-free survival (PFS). We devised survival stratification models based on the independent prognosticators and compared the model to the American Joint Committee on Cancer (AJCC) staging system using Harrell's concordance index (c-index). Our results demonstrated that total TLG (the combination of primary tumor and nodal total lesion glycolysis) and age were independent risk factors for unfavorable OS (p < 0.001 and p = 0.001) and PFS (both p < 0.001), while the Eastern Cooperative Oncology Group scale independently predicted poor OS (p = 0.022). Our models based on the independent prognosticators outperformed the AJCC staging system (c-index = 0.732 versus 0.544 for OS and c-index = 0.672 versus 0.521 for PFS, both p < 0.001). Our results indicate that incorporating total TLG with clinical factors may refine risk stratification in nodal metastatic NSCLC patients and may facilitate tailored therapeutic strategies in this patient group.

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

Abstract: Importance Few studies have examined the clinicopathological characteristics and prognoses of patients with hepatoid adenocarcinoma of the stomach (HAS). Objective To explore the clinicopathological characteristics and prognoses of patients with HAS and develop a nomogram to predict overall survival (OS). Design, Setting, and Participants 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. Main Outcomes and Measures 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. Results 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). Conclusions and Relevance 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.

Nomogram for predicting postoperative cancer-specific early death in patients with epithelial ovarian cancer based on the SEER database: a large cohort study.

Abstract: Purpose Ovarian cancer is a common gynecological malignant tumor. Poor prognosis is strongly associated with early death, but there is no effective tool to predict this. This study aimed to construct a nomogram for predicting cancer-specific early death in patients with ovarian cancer. Methods We used data from the Surveillance, Epidemiology, and End Results database of patients with ovarian cancer registered from 1988 to 2016. Important independent prognostic factors were determined by univariate and multivariate logistic regression and LASSO Cox regression. Several risk factors were considered in constructing the nomogram. Nomogram discrimination and calibration were evaluated using C-index, internal validation, and receiver operating characteristic (ROC) curves. Results A total of 4769 patients were included. Patients were assigned to the training set (n = 3340; 70%) and validation set (n = 1429; 30%). Based on the training set, eight variables were shown to be significant factors for early death and were incorporated in the nomogram: American Joint Committee on Cancer (AJCC) stage, residual lesion size, chemotherapy, serum CA125 level, tumor size, number of lymph nodes examined, surgery of primary site, and age. The concordance indices and ROC curves showed that the nomogram had better predictive ability than the AJCC staging system and good clinical practicability. Internal validation based on validation set showed good consistency between predicted and observed values for early death. Conclusion Compared with predictions made based on AJCC stage or residual lesion size, the nomogram could provide more robust predictions for early death in patients with ovarian cancer.

Impact of Bile Duct Tumor Thrombus on the Long-Term Surgical Outcomes of Hepatocellular Carcinoma Patients: A Propensity Score Matching Analysis.

Abstract: Hepatectomy with tumor thrombectomy is the preferred treatment option for hepatocellular carcinoma (HCC) patients with bile duct tumor thrombus (BDTT); however, the impact of BDTT on their prognosis is unclear. We aimed to investigate the long-term surgical outcomes of HCC patients with BDTT. The data of HCC patients with and without BDTT who underwent hepatectomy were retrospectively reviewed and the long-term outcomes were compared. For propensity score matching (PSM) analysis, patients were matched in a 1:1 ratio. Subgroup analysis was conducted according to the American Joint Committee on Cancer (AJCC) staging system. Before PSM, HCC patients with BDTT had more advanced tumor stages and adverse clinicopathological features. Recurrence-free survival (RFS) and overall survival (OS) were significantly higher in the non-BDTT group before PSM (RFS, p < 0.001; OS, p < 0.001), while after PSM, the BDTT group had significantly poorer RFS (p = 0.025). There was no difference in OS between the groups (p = 0.588). Subgroup analysis showed that RFS and OS in AJCC stage I–II patients were significantly poorer in the BDTT group; no differences were found in the AJCC stage III group before or after PSM. When the presence of BDTT was recommended to increase the AJCC staging system by one stage in AJCC stage I–II patients, the predictive ability for RFS and OS was higher. BDTT was associated with significantly poorer long-term surgical outcomes in AJCC stage I–II patients. A modified AJCC staging system including BDTT status in stage I–II might have a better prognostic ability.

Revisiting the AJCC staging system of adrenocortical carcinoma.

Abstract: OBJECTIVE To evaluate the performance characteristics of AJCC 7th and 8th staging systems among patients with adrenal cortical carcinoma. METHODS Surveillance, Epidemiology, and End Results (SEER) 18-registry was accessed and patients with adrenocortical carcinoma who were diagnosed 2010-2015 with complete information about AJCC 7th staging system were included. AJCC 8th staging system information was then reconstructed for each patient using available TNM staging variables. Kaplan-Meier overall survival estimates, multivariable Cox regression analysis, and concordance index (C-statistic) were used to examine the performance characteristics of both staging systems. RESULTS A total of 574 patients with a diagnosis of adrenocortical carcinoma were included in the current analysis. Using Kaplan-Meier survival estimates, overall survival was compared among different AJCC stages for both versions; and the P value was significant (< 0.001) for both comparisons. C-statistic was then calculated for both staging systems and the results were as follows: for AJCC 7th version: 0.726 (95% CI 0.683-0.769); and for AJCC 8th version: 0.745 (95% CI 0.704-0.786). Patients with M1 disease (stage IV according to AJCC 8th edition) were then divided according to the extent of distant metastases into single versus multiple sites of metastases. Using Kaplan-Meier survival estimates, patients with a single site of metastases have better overall survival (P = 0.006). A C-statistic for a hypothetical modification of AJCC 8th staging system subdividing stage IV patients into IVA and IVB based on the number of metastatic sites was: 0.753 (95% CI 0.713-0.794). CONCLUSIONS There is a minimal difference in the prognostic performance between both versions of the AJCC staging system. Subdivision of stage IV cancer into stage IVA and IVB (according to the number of organs with metastatic deposits) should be considered in subsequent versions of adrenocortical carcinoma staging.

Assessment of the AJCC staging system of pheochromocytomas/paragangliomas.

Abstract: This study aims to assess the performance of the AJCC 8th staging system for pheochromocytomas and paragangliomas (PPGLs) based on a population-based cohort. Surveillance, epidemiology, and end results (SEER)-18 registry database was reviewed, and patients with PPGLs diagnosed 2004–2015 were reviewed. AJCC stage for each patient was reconstructed from the collaborative stage dataset. Kaplan–Meier survival estimates according to the AJCC stage were reviewed, and multivariable Cox regression analysis was conducted to determine the impact of AJCC stages on overall and cancer-specific survival. A total of 416 patients with PPGLs were eligible and were included in the current analysis. Using Kaplan–Meier survival estimates, patients with stage IV seem to have the worst overall survival (P < 0.001). When the results were stratified by the site of origin (adrenal vs. extra-adrenal), similar findings were observed in both strata (P < 0.001 in each stratum). Using multivariable Cox regression analysis for overall survival, HR for stage I vs. II was: 0.59; (95% CI: 0.27–1.27), HR for stage II vs. III: 0.82; (95% CI: 0.41–1.63), and HR for stage III vs. IV was: 0.37; (95% CI: 0.24–0.58). Likewise, for cancer-specific survival, HR for stage I vs. II was: 0.72; (95% CI: 0.26–1.97), HR for stage II vs. III: 0.64; (95% CI: 0.25–1.63), and HR for stage III vs. IV was: 0.33; (95% CI: 0.19–0.56). C-statistic for AJCC 8th staging system was: 0.723 (95% CI: 0.669–0.776). Further improvements within AJCC 8th edition are possible, including the inclusion of the extent of metastatic disease in the subclassification of stage IV disease, and not considering primary tumor site when assigning T stage.