8th Edition TNM Staging System Research Articles

A Nomogram Based on Platelet Distribution Width-to-Lymphocyte Ratio to Predict Overall Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma.

To evaluate the prognostic significance of platelet distribution width-to-lymphocyte ratio (PDWLR) in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Moreover, a nomogram based on PDWLR was built and validated to predict the overall survival (OS) of this population. All LA-NPC patients who were diagnosed and treated between January 2015 and December 2017 at Guangxi Medical University Cancer Hospital were included. Cox regression analyses were performed to assess PDWLR and clinical features that might affect OS to screen for independent predictors. The independent predictors and important clinical variables were used to build and validate a nomogram for predicting OS. Then, the capability of the model was estimated by discrimination, calibration and clinical usefulness. Risk stratification was conducted using the nomogram-calculated risk score, and the comparison of survival in the high-risk group and the low-risk group was through Kaplan-Meier method. This study included 746 LA-NPC patients. Multivariate Cox analysis suggested that age (hazard ratio [HR]: 1.81, 95% confidence interval [CI]: 1.18-2.78, P = 0.007), gender (HR: 2.03, 95% CI: 1.12-3.68, P = 0.019), pre-treatment plasma Epstein-Barr virus (EBV) DNA (HR: 1.55, 95% CI: 1.01-2.39, P = 0.047), PDWLR (HR: 2.61, 95% CI: 1.67-4.09, P < 0.001) were independent predictors of OS. Compared to the 8th edition TNM staging system, the nomogram based on the above four factors and important clinical variables (T stage and N stage) demonstrated better predictive performance. Moreover, the model had the ability to identify individuals at high risk. PDWLR was a promising negative predictor for patients with LA-NPC. The nomogram based on PDWLR demonstrated better predictive performance than the current staging system.

A Nomogram Based on Platelet Distribution Width-to-Lymphocyte Ratio to Predict Overall Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma.

To evaluate the prognostic significance of platelet distribution width-to-lymphocyte ratio (PDWLR) in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). Moreover, a nomogram based on PDWLR was built and validated to predict the overall survival (OS) of this population. All LA-NPC patients who were diagnosed and treated between January 2015 and December 2017 at Guangxi Medical University Cancer Hospital were included. Cox regression analyses were performed to assess PDWLR and clinical features that might affect OS to screen for independent predictors. The independent predictors and important clinical variables were used to build and validate a nomogram for predicting OS. Then, the capability of the model was estimated by discrimination, calibration and clinical usefulness. Risk stratification was conducted using the nomogram-calculated risk score, and the comparison of survival in the high-risk group and the low-risk group was through Kaplan-Meier method. This study included 746 LA-NPC patients. Multivariate Cox analysis suggested that age (hazard ratio [HR]: 1.81, 95% confidence interval [CI]: 1.18-2.78, P = 0.007), gender (HR: 2.03, 95% CI: 1.12-3.68, P = 0.019), pre-treatment plasma Epstein-Barr virus (EBV) DNA (HR: 1.55, 95% CI: 1.01-2.39, P = 0.047), PDWLR (HR: 2.61, 95% CI: 1.67-4.09, P < 0.001) were independent predictors of OS. Compared to the 8th edition TNM staging system, the nomogram based on the above four factors and important clinical variables (T stage and N stage) demonstrated better predictive performance. Moreover, the model had the ability to identify individuals at high risk. PDWLR was a promising negative predictor for patients with LA-NPC. The nomogram based on PDWLR demonstrated better predictive performance than the current staging system.

Challenges in the Assessment of Medullary Bone Invasion in Oral Cavity Cancers and Its Prognostic Significance.

As per AJCC 8th edition TNM staging system, bone invasion is a poor prognostic marker that upstages oral cavity squamous carcinoma (OSCC) to pT4a. Cortical erosion alone of bone or tooth socket by a gingival primary is not sufficient to upstage a tumour. The differentiation of cortical erosion from invasion through the cortical bone into the medulla is often challenging, limiting accurate staging. This review aims to assess the difficulties in differentiating cortical erosion from medullary invasion and evaluate the prognostic significance of different patterns of bone involvement. A retrospective review of OSCC with primary curative surgery and bone resection treated at a single-center over 10years, was performed to assess the prognostic significance of bone invasion. Hematoxylin-eosin stained slides of a subset of cases were re-reviewed in a planned manner to assess difficulties in precise categorization (no invasion/erosion/cortical invasion and medullary invasion), evaluate interobserver agreement, and correlate with clinical outcome. Five hundred and ninety patients were included, with a median follow-up of 28months. On univariate analysis, the 3-year local, nodal and distant metastasis control were not significantly different in the 3 groups of no invasion, erosion, and invasion (p = 0.43, 0.47, and 0.47, respectively). Overall survival (OS) at 3years was 78.1% and disease-free-survival(DFS) was 63.7% in the entire cohort. On univariate analysis, there was significant difference in OS and DFS based on these groups. This did not translate into independent prognostic benefit on multivariable analysis (p = 0.75 and 0.19, respectively). The independent prognostic factors were margin positivity, tumor differentiation, perineural invasion and pathological nodal involvement. Planned re-review of a subset of 202 cases resulted in a change in bone involvement category in 26/202 cases, which was mainly due to difficulty in assessing cortico-medullary junction near the tooth socket and bone fragmentation. The assessment showed moderate to near complete agreement (kappa 0.59-0.82) between 2 observers. Our study shows that bone involvement is not an independent prognostic marker and there is no specific correlation of medullary invasion with outcome over those that showed cortical erosion. Several factors contribute to difficulties and interobserver variability in assessing bone involvement.

Prediction values of tertiary lymphoid structures in the prognosis of patients with left- and right-sided colon cancer: a multicenter propensity score-matched study.

Tertiary lymphoid structures (TLS) are the lymphocyte aggregates that play a key role in the vast majority of solid tumors including colon cancer, displaying an antitumor effect under most circumstances. The heterogeneity between left- and right-sided colon cancer (LCC and RCC) encompasses various aspects, such as clinical manifestations, pathological features, and immune responses. However, the function and prognostic significance of TLS within LCC and RCC have yet to be fully understood. A retrospective analysis was performed on 2612 patients who underwent radical resection for LCC or RCC without distant metastasis in multiple medical centers. Utilizing propensity score matching, 121 patients with LCC and 121 patients with RCC were selected for the training set. An external validation set including 64 patients with LCC and 64 patients with RCC were also employed. Hematoxylin-eosin and immunohistochemical staining were used to assess TLS and the proportion of various immune cells. Clinical characteristics and prognostic values of TLS in patients with LCC and RCC were analyzed. Nomograms were constructed for LCC and RCC to predict 3-year and 5-year overall survival (OS), respectively. For LCC and RCC patients, TLS was located in the interstitial region or outside the tumor tissue and mainly consisted of B cells and T cells. The TLS quantity and density in RCC were higher than those of LCC. In multivariate Cox regression analysis, TLS density ( P =0.014), vascular invasion ( P =0.019), and AJCC stage ( P =0.026) were independent prognostic factors for 5-year OS of RCC. For LCC patients, AJCC stage ( P =0.024), tumor differentiation ( P =0.001), and tumor budding ( P =0.040) emerged as independent prognostic factors for 5-year OS. Similar results were obtained in the external verification set. Separate nomograms for RCC and LCC were developed, displaying improved prediction performance compared to the AJCC 8th edition TNM staging system. Differences in TLS quantity and density were observed between LCC and RCC, suggesting that a nomogram based on TLS density could more effectively predict survival for RCC patients. Furthermore, a nomogram based on tumor budding was recommended for better prediction of LCC patient survival. Taken together, these results suggested that the immune and clinical characteristics of colon cancer at left and right side were substantially different, which may lead to the use of different prediction model and the development of individual treatment strategy.

Newly proposed survival staging system for poorly differentiated thyroid cancer: a SEER-based study.

Despite the recent release of the 8th edition TNM staging system, the risk stratification for poorly differentiated thyroid cancer (PDTC) remains controversial. Retrospective study. SEER database and the First Hospital of China Medical University (FHCMU) database. Between 2004 and 2015, 1201 PDTC patients from the SEER database were enrolled to propose a new staging system. 38 PDTC patients were included from the FHCMU. A retrospective analysis of 1201 PDTC cases was performed, and a new staging classification was developed as follows: stage I: age < 55 and T1/any N/M0 (n = 127, 10.57%); stage II: age < 55 and T2-4/any N/M0 or age ≥ 55 and T1-2/any N/M0 (n = 523, 43.55%); stage III: age < 55 and any T/N0/M1 or age ≥ 55 and any T3/any N/M0 (n = 239, 19.90%); stage IV: age < 55 and any T/N1/M1 or age ≥ 55 and T4/any N/M0, and T/any N/M1 (n = 312, 25.98%). The 10-year disease-specific survival rates of patients in the new stages I, II, III, and IV were 97.9%, 77.9%, 35.3%, and 12.1%, respectively. The proportion of variation explained (PVE) for disease-specific survival of the proposed system was higher than that of the 8th AJCC TNM staging (30.61% vs. 27.15%). The accuracy of the staging system was verified in 38 PDTC patients from the FHCMU. The proposed staging system provided a more accurate risk stratification for PDTC patients. The new staging model may facilitate the design of personalized treatment strategies for PDTC patients.

MA04.05 T3 Defining Features Influence Long Term Survival after Resection of T3N0M0 NSCLC

Despite improvements from the 7th edition, the T3 category in the 8th edition TNM staging system is still heterogeneous. We evaluated long-term survival in patients with non-small cell lung cancer (NSCLC) classified as T3N0M0 by different T3 tumor features to identify ways to improve the prognostic utility of the classification.

The Poor Prognosis of Patients with Stage III Gastric Cancer after D2 Dissection Is Mainly due to Lymphatic Metastasis, Especially the Metastasis of No.12a LN: A Nested Case-Control Study

Background: The prognosis of stage III gastric cancer (GC) patients based on the 8th edition TNM staging system after D2 dissection was still heterogeneous. We aimed to explore clinicopathological reasons that led to the poor prognosis of these patients, especially from a surgical aspect. Methods: We divided 320 stage III GC patients who underwent distal or total gastrectomy with D2 lymphadenectomy into group 1 and group 2, according to the disease-free survival (DFS), and compared the clinicopathological features between these 2 groups. Then, we divided group 1 into group 1D and group 1T and group 2 into group 2D and group 2T, according to distal or total gastrectomy. Finally, we compared the status of lymph node (LN) metastasis in each group of perigastric LN between the subgroups, respectively. Results: Univariate analyses revealed that patients’ LN metastasis was the only significant difference between group 1 and group 2 (p < 0.05). Compared with group 1D, the percentage of patients who had metastatic LN in all groups of the perigastric LN (included No.1, 3, 4sb, 4d, 5, 6, 7, 8a, 9, 11p and 12a) increased in group 2D. A similar tendency was found in group 2T (included No.1, 2, 3, 4sa, 4sb, 4d, 5, 6, 7, 8a, 9, 10, 11p, 11d and 12a) compared with group 1T. Further multivariate regression analyses revealed that the increases of group No.12a and 5 LN were significant (p < 0.05) in group 2D, the increases of group No.12a, 8a and 6 LN were significant (p < 0.05) in group 2T, respectively. Among these, the increases of group No.12a LNs were the most significant (p < 0.01). Conclusions: The poor prognosis of patients with stage III GC after D2 dissection is mainly due to lymphatic metastasis. The status of LN metastasis in the prognostic value of GC needs to be further enhanced in present staging systems. Maybe the metastasis of No.12a LN is the most significant poor prognostic factor of these patients. It points out that the dissection of No.12a LN should be carefully performed in radical gastrectomy.

Radical (chemo)radiotherapy in oropharyngeal squamous cell carcinoma: Comparison of TNM 7th and 8th staging systems

PurposeTo evaluate whether the 8th staging system is a better discriminator of overall survival (OS) than the 7th edition for oropharyngeal cancer patients after definitive (chemo)radiotherapy (CRT). Material and methodsData from oropharyngeal cancer patients treated with CRT with curative intent between 2010 and 2016 at Guy’s and St Thomas’ Hospitals were reviewed. Human papillomavirus (HPV) status was ascertained in all cases. Patients were staged using the 7th edition and the 8th edition TNM staging system. Demographics, tumor characteristics and treatment response data were included in univariate and multivariate analysis for OS. OS and disease-free survival (DFS) were estimated using the Kaplan-Meier method. In addition, a multivariate survival Cox regression analysis of several clinical variables was performed. ResultsA total of 273 patients were included. The median follow-up was 4.7 years. Overall 63 patients died. In multivariate analysis, HPV status, complete response at 3 months and ≤21 units/week alcohol were prognostic for OS. For the entire cohort, the 5-year OS and DFS rates were 78.1% (95% confidence interval CI 0.719–0.831) and 73.9% (95% CI 0.677–0.792), respectively. Better stratification of OS and DFS was recorded by 8th edition for the entire cohort. In HPV-positive cases, risk stratification based on tobacco smoking and nodal stage resulted in statistically higher discrimination in OS rates (5-year OS 90.7% in low risk patients and 84.6% in intermediate risk, p = 0.05) and DFS rates (5-year DFS 91.5% in low risk and 76.1% in intermediate risk, p = 0.001). ConclusionThe 8th edition TNM staging system provides better OS stratification in oropharyngeal cancer after definitive CRT compared with the 7th edition. Other clinical variables, such as complete response at 3 months, alcohol and tobacco smoking, should also be considered in future classifications as they provide additional risk stratification information in both HPV-positive and HPV-negative disease.

Dataset for the reporting of carcinoma of the bladder-cystectomy, cystoprostatectomy and diverticulectomy specimens: recommendations from the International Collaboration on Cancer Reporting (ICCR).

The International Collaboration on Cancer Reporting (ICCR) is a not for profit organisation whose goal is to produce standardised internationally agreed and evidence-based datasets for pathology reporting. With input from pathologists worldwide, the datasets are intended to be uniform and structured. They include all items necessary for an objective and accurate pathology report which enables clinicians to apply the best treatment for the patient. This dataset has had input from a multidisciplinary ICCR expert panel. The rationale for some items being required and others recommended is explained, based on the latest literature. The dataset incorporates data from the World Health Organization (WHO) 2016, and also from the latest (8th edition) TNM staging system of the American Joint Committee on Cancer (AJCC). Fifteen required elements and eight recommended items are described. This dataset provides all the details for a precise and valuable pathology report required for patient management and prognostication. This dataset is intended for worldwide use, and should facilitate the collection of standardised comparable data on bladder carcinoma at an international level.

The Effect of Resection Margin Distance and Invasive Component Size on Recurrence After Sublobar Resection in Patients With Small (≤2 Cm) Lung Adenocarcinoma.

When performing sublobar resection for lung cancer, the margin distance should exceed the tumor size. However, instead of total tumor size, the 8th edition TNM staging system has adopted the size of invasive component for the T stage. The aim of this study was to determine whether the prognosis was satisfactory when the resection margin distance was greater than the invasive component size instead of the total tumor size. From 2008 to 2017, 193 consecutive patients were diagnosed with lung adenocarcinoma (invasive component size ≤2cm) and underwent sublobar resection. We analyzed risk factors for recurrence using clinicopathological factors including margin/invasive component ratio (resection margin distance/invasive component size). Mean tumor size was 1.4 (±0.5) cm and the mean invasive component size was 0.8cm (±0.5). In the multivariate analysis, neither resection margin distance (cm) nor margin/tumor ratio (resection margin distance/tumor size) was significant risk factors for recurrence. On the other hand, the margin/invasive component ratio (hazard ratio =0.035, p = 0.043) and the SUVmax (hazard ratio =1.993, p = 0.033) were significant risk factors for recurrence. When sublobar resection is performed for small (invasive component size ≤2cm) adenocarcinomas of the lung, the resection margin distance should be larger than the invasive component size. Sublobar resection is not an appropriate treatment for lung adenocarcinoma with high SUVmax.

MA05.02 Log Odds of Positive Lymph Nodes Predicts Overall Survival and the Benefit of Postoperative Radiotherapy in Malignant Pleural Mesothelioma

Nodal categories of malignant pleural mesothelioma (MPM) are mostly adopted from lung cancer staging criteria and the N descriptors in the eighth edition of TNM staging system have not been fully verified. We aimed to evaluate the effectiveness of the current N descriptors and a novel prognosticator—the log odds of positive lymph nodes (LODDS)—in predicting overall survival (OS) and postoperative radiotherapy (PORT) benefit in MPM. Patients in the Surveillance, Epidemiology, and End Results (SEER) database with MPM undergoing surgery and lymph nodes examination were extracted and restaged according to the 8th edition TNM staging system. LODDS was calculated as loge[(positive nodes count+0.5)/(negative nodes count+0.5)]. X-tile software determined the optimal cut-point for LODDS. Log-rank tests along with Cox regression analyses were adopted for survival analyses. Harrell's C-index statistic measured discriminatory ability and prognostic performance. A total of 534 patients were enrolled in this study. N descriptors were unevenly distributed. Most cases were staged as N0 (51.9%) and N1 (47.0%), with only 1.1% staged as N2. The eighth edition N descriptors failed to clarify the survival difference between adjacent categories and were incapable of predicting PORT benefit. The cut-points for LODDS were classified as follows: LODDS1 (≤-2.61), LODDS2 (-2.56≤LODDS≤0.62), and LODDS3 (≥0.87). The median survival of LODDS1 was 23.1 months compared with 17.9 months (HR=1.397, P=0.005) and 13.0 months (HR=2.317, P<0.001) for LODDS2 and LODDS3, respectively. The survival curves stratified by LODDS separated nicely without overlapping and the benefit of PORT was limited to cases with LODDS3 (≥0.87). LODDS also provided better C-index than the conventional N descriptors. LODDS performs better than N descriptors for predicting survival and benefits of PORT in resected MPM, and it could be considered as a potential parameter to compensate for defects in the 8th AJCC TNM staging for MPM.

PL04.03 The Relevance of an International Database for the Study of Thymic Neoplasms

Until the 8thedition of the AJCC/UICC TNM classification of malignant tumours went into effect, no official stage classification was available for thymic malignancies. Some classification systems had been proposed but were generally developed from a limited number of patients and not usually tested in an independent dataset. The system developed by Dr. Akira Masaoka in 1981 did undergo external validation and was widely adopted. However, the adoption of these proposed systems in different institutions and regions was hampered by a lack of uniform nomenclature and varying interpretations of definitions. The current (8thedition) TNM stage classification for thymic malignancies endorsed by AJCC and UICC was informed by a database with 10,808 cases of thymic malignancies from 105 sites worldwide, compiling cases contributed by ITMIG (including patients from North and South America, European, and Korean (KART) and Chinese (ChART) institutions), Japan (JART), and Europe (ESTS) with funding and coordination by IASLC and Cancer Research and Biostatistics (CRAB), with the specific intent of developing a TNM based staging system for these malignancies. The IASLC Stating and Prognostic Factors Committee - Thymic Domain (SPFC-TD) conducted a web-based cross-sectional survey to assess the implementation of the 8thEdition TNM staging system in the thoracic community. The survey was sent to the major thymic organizations (ITMIG, ESTS, KART, ChART, RYTHMIC, JART) in addition to IASLC membership. A new database to inform the 9thedition TMN staging system is under development to provide updated follow-up from the institutions contributing to the 8thedition database, add additional institutions, and add new cases collected prospectively. According to the survey results, the TNM stage classification of thymic tumors has gained a reasonable acceptance in the scientific community, while the Masaoka stage system remains widely employed. An increased attention to the N descriptor seems to have been incorporated. There is high awareness of the new staging system. The current efforts of the Thymic Domain of the IASLC Staging and Prognostic Factors Committee focus on expanding and updating the database used for the 8thedition to further refine the stage definitions and includes updated follow-up on patients from Turkey, the ESTS, JART, ChART and KART, plus data collected prospectively from ChART. The database created to inform the 9thedition of TNM staging for thymic malignancies will allow for refinement and adjustment of the 8thedition system and attempt to address any perceived deficiencies of the current system. An overview of the current state of the database will be presented at the meeting in Barcelona.

Clinical impact of segmental renal vein invasion on recurrence in patients with clinical T1 renal cell carcinoma undergoing partial nephrectomy.

This study evaluated the clinical significance of pathological factors associated with T3a upstaging according to the American Joint Committee on Cancer/Union for International Cancer Control 8th edition TNM-staging system in patients with clinical T1 renal cell carcinoma undergoing definitive surgery. We retrospectively investigated 418 patients with renal cell carcinoma who underwent partial or radical nephrectomy at our institution between 2006 and 2016. Surgical specimens were grossly and microscopically re-reviewed with respect to extrarenal extension patterns by two urological pathologists. Kaplan-Meier analysis and Cox regression were used to determine the impact of the factors associated with pathological stage T3a on recurrence-free survival. Harrell's c-index was used to compare the prognostic accuracy of the current and previous staging systems. Overall, the 5-year recurrence-free survival was 94.5% (median follow-up duration, 60.8months). Of 418 patients, 46 (11.0%) were upstaged to pathological stage T3a, including 12/267 (4.5%) and 34/151 (22.5%) in the partial and radical nephrectomy groups, respectively. Among these upstaged patients, partial nephrectomy was significantly associated with a higher recurrence rate than radical nephrectomy (5-year recurrence-free survival: 48.9 vs. 83.9%, P = 0.0172). Although perinephric fat invasion had the highest c-index in all patients (0.580-0.679), microscopic segmental renal vein invasion was a significant predictor of recurrence in patients undergoing partial nephrectomy (c-index, 0.60). Assessing microscopic segmental renal vein invasion, which has been included in the current staging system recently, is essential to accurately predict the oncological outcome in the era of partial nephrectomy for clinical T1 renal cell carcinoma.

Nomograms for predicting overall survival and cancer-specific survival in patients with surgically resected intrahepatic cholangiocarcinoma.

PurposeTo develop and validate nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) in patients with surgically resected intrahepatic cholangiocarcinoma (ICC).Patients and methodsThe nomograms were developed using a development cohort of 947 ICC patients after surgery selected from Surveillance, Epidemiology, and End Results database, and externally validated using a training cohort of 159 patients admitted at our institution. Nomograms for OS and CSS were established based on the independent prognostic factors identified by COX regression models and Fine and Grey’s models, respectively. The performance of the nomograms was validated internally and externally by using the concordance index (c-index), and calibration plot, and compared with that of AJCC 8th edition TNM staging system by using c-index and decision curve analysis.ResultsAge, T stage, M stage, lymph node ratio (LNR) level and tumor grade were independent prognostic predictors for OS in ICC patients, while T stage, M stage, LNR level and tumor grade were independent prognostic predictors for CSS. Nomogram predicting OS was with a c-index of 0.751 on internal validation and 0.725 up to external validation, while nomogram for CSS was with a c-index of 0.736 on internal validation and 0.718 up to external validation. Calibration plots exhibited that the nomograms-predicted and actual OS/CSS probabilities were fitted well on both internal and external validation. Additionally, the nomograms exhibited superiority over AJCC 8th edition TNM staging system with higher c-indices and net benefit gains, in predicting OS and CSS in ICC patients after surgery.ConclusionThe constructed nomograms could predict OS and CSS with good performance, which could be served as an effective tool for prognostic evaluation and individual treatment strategies optimization in ICC patients after surgery in clinical practice.

Prognosis after wedge resection in patients with 8th edition TNM stage IA1 and IA2 non-small cell lung cancer.

According to the 8th edition TNM classification for non-small cell lung cancer (NSCLC), tumor stage (T) is determined by the maximum size of the invasive component, without the lepidic component, and the T category has been further subdivided. We investigated the indications for wedge resection using the 8th edition TNM staging system, which measures only the size of the invasive component in tumor size. We compared 5-year disease-free survival (DFS) rates in 429 consecutive patients with 8th edition stage IA1 and IA2 NSCLC who underwent lobectomy or wedge resection from 2007 to 2017. We also analyzed the risk factors for recurrence after surgical resection. There were no significant differences in clinicopathological factors or 5-year DFS in patients with stage IA1 disease (5-year DFS 95.0%, lobectomy, vs. 91.6%, wedge resection; P=0.435). For patients with stage IA2 tumors, the 5-year DFS was 88.3% after lobectomy and 74.0% after wedge resection (P=0.118). There were significant differences in clinicopathological characteristics between lobectomy and wedge resection groups in stage IA2 NSCLC. On multivariate analysis, serum CEA level [hazard ratio (HR) =1.040, P=0.046] and lymphovascular invasion (HR =2.664, P=0.027), but not wedge resection, were significant risk factors for recurrence in stage IA2 NSCLC. On multivariate analysis for recurrence risk after wedge resection in stage IA1 and stage IA2 NSCLC, only the width of the resection margin was associated with recurrence. Wedge resection may be an acceptable procedure in stage IA1 NSCLC. When performing wedge resection, it is necessary to ensure a sufficient resection margin distance.

Disease-Free Survival for Patients with Thin Melanomas according to the American Joint Committee on Cancer 8th Edition

Background: The recently implemented AJCC 8th edition TNM staging system for malignant melanoma (MM) changed the definition for T1a and T1b tumours. Objectives: To analyse differences in disease-free survival (DFS) among patients with thin MM staged according to both AJCC 7th and 8th editions. Methods: An observational study including 285 patients with cutaneous thin MM (thickness ≤1 mm). Cases were staged as T1a and T1b using both 7th and 8th editions. Neither regional nor visceral diseases were present at diagnosis. DFS curves were generated according to the Kaplan-Meier method. Results: An 8% shift of patients from a T1a towards a T1b stage group was observed after applying the AJCC 8th edition. According to this 8th edition, DFS for T1a patients was significantly longer than for T1b patients (log-rank test; p = 0.005); 5-year DFS for T1a and T1b was 100 and 95%, respectively (Wilcoxon test; p = 0.002). According to the AJCC 7th edition, DFS did not significantly differ for T1a and T1b patients; 5-year DFS for T1a and T1b was 99 and 97%, respectively (p > 0.05). Conclusions: The AJCC 8th edition seems to be a better tool for staging thin melanomas.

Evaluation of the Eighth Edition of the American Joint Committee on Cancer TNM Staging System for Gastric Cancer: An Analysis of 7371 Patients in the SEER Database.

Objective To investigate the validity of the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system for gastric cancer. Methods The clinicopathologic data of 7371 patients who were diagnosed with gastric cancer and had 16 or more involved lymph nodes (LNs) were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database and retrospectively reviewed. Results Stage migration occurred primarily during stage III between the 7th and 8th edition TNM staging systems. Stages IIIB and IIIC in the 7th edition staging system were divided in the 8th edition and had obvious differences in survival rates (both P < 0.001). The 8th edition TNM stages IIIC and IV showed similar survival rates (P = 0.101). The prognosis of patients with T4aN3bM0 was not different from that of patients with TxNxM1 (P = 0.433), while the prognosis of patients with T4bN3bM0 was significantly poorer than that of patients with TxNxM1 (P = 0.008). A revised TNM system with both T4aN3bM0 and T4bN3bM0 incorporated into stage IV was proposed. Multivariable regression analysis showed that the revised TNM system, but not the 7th and 8th editions, was an independent factor for disease-specific survival (DSS) in the third step of the analysis. Further analyses revealed that the revised TNM system had superior discriminatory ability to the 8th edition staging system, which was also an improvement over the 7th edition staging system. Conclusion The 8th edition of the AJCC TNM staging system is superior to the 7th edition for predicting the DSS rates of gastric cancer patients. However, for better prognostic stratification, it might be more suitable for T4aN3bM0/T4bN3bM0 to be incorporated into stage IV in the 8th edition TNM staging system.

A Nomogram for Predicting Cancer-Specific Survival of TNM 8th Edition Stage I Non-small-cell Lung Cancer.

Models for predicting the survival outcomes of stage I non-small-cell lung cancer (NSCLC) defined by the newly released 8th edition TNM staging system are scarce. This study aimed to develop a nomogram for predicting the cancer-specific survival (CSS) of these patients and identifying individuals with a higher risk for CSS. A total of 30,475 NSCLC cases were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We identified and integrated the risk factors to build a nomogram. The model was subjected to bootstrap internal validation with the SEER database, and external validation with a multicenter cohort of 1133 patients from China. The difference in the impact of adjuvant chemotherapy on model-defined high- and low-risk patients was examined using the National Cancer Database (NCDB). Eight independent prognostic factors were identified and integrated into the model. The calibration curves showed good agreement. The concordance index (C-index) of the nomogram was higher than that of the staging system (IA1, IA2, IA3, and IB) (internal validation set 0.63 vs. 0.56; external validation set 0.66 vs. 0.55; both p < 0.01). Specifically, 21.7% of stage IB patients (7.5% of all stage I) were categorized into the high-risk group (score > 30). There was a significant interaction effect between the adjuvant chemotherapy and risk groups in the NCDB cohort (p = 0.003). We established a practical nomogram to predict CSS for 8th edition stage I NSCLC. A prospective study is warranted to determine its role in identifying adjuvant chemotherapy candidates.

Tumor-Infiltrating NETs Predict Postsurgical Survival in Patients with Pancreatic Ductal Adenocarcinoma.

Tumor-infiltrating neutrophils (TINs) indicate poor prognosis for patients with pancreatic ductal adenocarcinoma (PDAC). Activated neutrophils can generate neutrophil extracellular traps (NETs). Little is known about the presence and prognostic significance of tumor-infiltrating NETs in PDAC. This study enrolled 317 patients, in two independent sets (training and validation), who underwent curative pancreatectomy for PDAC in Shanghai Cancer Center. TINs and NETs were identified by immunohistochemical staining for CD15 and citrullinated histone H3, respectively. The relationship between clinicopathological features and outcomes was analyzed. Accuracy of prognostic prediction models was evaluated using concordance index (C-index) and Akaike information criterion (AIC). NETs were associated with OS (both, P < 0.001) and RFS (both, P < 0.001) in the training and validation sets. Tumor-infiltrating NETs predicted poor postsurgical survival of patients with PDAC. Moreover, multivariate analysis identified NETs and AJCC TNM stage as two independent prognostic factors for OS and RFS. Combination of NETs with the 8th edition TNM staging system (C-index, 0.6994 and 0.6669, respectively; AIC, 1067 and 1126, respectively) generated a novel model that improved the predictive accuracy for survival in both sets (C-index, 0.7254 and 0.7117, respectively; AIC, 1047 and 1102, respectively). The model combining presence of NETs with the 7th edition AJCC TNM staging system also had improved predictive accuracy. NETs were an independent prognostic factor in PDAC and incorporation of NETs along with the standard TNM stating system refined risk-stratification and predicted survival in PDAC with improved accuracy.

An updated and validated PET/CT volumetric prognostic index for non-small cell lung cancer

ObjectivesWhole-body metabolic tumor volume (MTVWB) and TNM staging are independent prognostic factors for overall survival (OS) in non-small cell lung cancer (NSCLC). We aimed to update and validate the PET/CT volumetric prognostic index (PVP index) using the new 8th edition TNM staging system to evaluate its prognostic power versus TNM staging and MTVWB alone. Materials and MethodsThis study was a retrospective analysis of 949 non-small cell lung cancer (NSCLC) patients diagnosed between 2004 and 2014. Clinical TNM stage, MTVWB, age and gender, tumor histology type at the initial staging PET/CT exam, as well as treatment history and long-term survival data were obtained. Patients were randomly assigned to modeling or validation group. Univariate and multivariate Cox regression analyses were performed to compare PVP index, TNM stage, and MTVWB in the validation group. ResultsThe updated PVP index included the 3 variables TNM stage, and MTVWB and age. Univariate Cox models showed significant association of PVP index with overall survival (OS) in patients with NSCLC (with Hazard ratio HR = 2.88 in the validation group, p < 0.001). The C-statistic of the PVP index (C-statistic = 0.71 in the validation group) was significantly greater than that of 8th edition TNM staging (C-statistic = 0.68, p = 0.029), MTVWB (C-statistic = 0.68, p = 0.001), and patient age (C-statistic = 0.53, p < 0.001). Multivariate Cox regression analyses demonstrated significant association of PVP index with OS (with HR = 2.80, p < 0.001) after adjusting patient’s gender and tumor histology. ConclusionsThe updated PVP index provides a quantitative risk assessment for NSCLC patients using 8th edition TNM staging, MTVWB, and age. The index provides a simple and practical way for the care team to incorporate the independent prognostic value of both the TNM stage and MTVWB. This approach can further improve the accuracy of overall survival prognosis.