American Joint Committee On Cancer 8th Research Articles

Validation of the American Joint Committee on Cancer Staging in Squamous Cell Carcinoma of the Vermilion Lip.

The vermilion lip is a unique anatomical junction between cutaneous and mucosal surfaces. Squamous cell carcinoma (SCC) of the vermilion lip (vlSCC) was previously classified as oral SCC (oSCC) under the American Joint Committee on Cancer (AJCC) 7th edition (AJCC7), but has been recategorized as a cutaneous SCC of the head and neck (HNcSCC) in the AJCC 8th edition (AJCC8). We investigated the locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) for the various pathological T categories and disease stages of vlSCC as per AJCC8. We performed a retrospective cohort study of 297 patients diagnosed with vlSCC between January 2004 and February 2019. For this study, vlSCC cases were staged according to both AJCC7 and AJCC8. Kaplan-Meier survival curves and Cox regression models were used to analyze differences in LRC, DFS, and OS between each pT category and disease stage, and log-rank tests were performed for subgroup analysis. Restaging of vlSCC using the AJCC8 resulted in 19% of patients being upstaged to pT3, and 16% being upstaged to stage III. No patients were downstaged in pT stage or overall stage. Our study shows that when the AJCC8 HNcSCC staging system is applied to vlSCC, there are important aberrations leading to unwarranted upstaging of pT1 and redundancy of pT2. Understanding of these limitations are important in considering treatment escalation.

The prognostic and predictive value of the 8th American Joint Committee on Cancer (AJCC) staging system among early breast cancer patients aged

This study respectively analyzed the prognostic value and the role in treatment decision-making [breast-conserving surgery (BCS) + radiotherapy (RT) or mastectomy (MAST)] of the 8th American Joint Committee on Cancer (AJCC) pathological prognostic staging system compared with the 7th AJCC anatomical staging system among early breast cancer patients aged <50 years. Patients with T1-2N0M0 breast cancer aged <50 years were extracted from the Surveillance, Epidemiology, and End Results database between 2010 and 2014. Breast cancer-specific survival (BCSS) was used as the primary endpoint. Chi-squared test, receiver operating characteristics analysis, Kaplan-Meier method, and multivariate Cox proportional models were used to conduct statistical analysis. A total of 22,640 female patients were identified, and 24.4% of them reallocated to new stage groups from the 7th to the 8th AJCC staging. Among them, 46.2% (n=10,450) and 53.8% (n=12,190) of patients received BCS + RT and MAST, respectively. The 8th AJCC staging system was an independent prognostic factor for BCSS. Patients treated with BCS + RT had better BCSS compared to those treated with MAST (P<0.001). According to the 8th AJCC staging, BCS + RT could improve 5-year BCSS compared with MAST in patients with stage IA (P=0.006) and stage IB (P=0.001) diseases, while comparable BCSS was found between the two treatment arms in patients' stage IIA disease (P=0.366). Multivariate analyses replicated similar findings after stratification by the 8th AJCC stages. In patients with T1-2N0 breast cancer and aged <50 years, the 8th AJCC pathological staging system provides accurate prognostic information than the 7th anatomical staging. BCS + RT is the optimal local management for stage IA and IB diseases, while it is the optional management in stage IIA disease according to the 8th AJCC staging.

Validation and modification of the AJCC 8th TNM staging system for pancreatic ductal adenocarcinoma in a Chinese cohort: A nationwide pancreas data center analysis.

ObjectiveTo validate the 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic ductal adenocarcinoma (PDAC) in a Chinese cohort of radically resected patients and to develop a refined staging system for PDAC.MethodsData were collected from the China Pancreas Data Center (CPDC) for patients with resected PDAC in 2016 and 2017, and cancer-specific survival (CSS) was evaluated using the Kaplan-Meier method and log-rank test. Univariate and multivariate analyses based on Cox regression were performed to identify prognostic factors. The recursive partitioning analysis (RPA), Kaplan-Meier method, and log-rank test were performed on the training dataset to generate a proposed modification for the 8th TNM staging system utilizing the preoperative carbohydrate antigen (CA)19-9 level. Validation was performed for both staging systems in the validation cohort.ResultsA total of 1,676 PDAC patients were retrieved, and the median CSS was significantly different between the 8th TNM groupings, with no significant difference in survival between stage IB and IIA. The analysis of T and N stages demonstrated a better prognostic value in the N category. Multivariate analysis showed that the preoperative serum CA19-9 level was the strongest prognostic indicator among all the independent risk factors. All patients with CA19-9 >500 U/mL had similar survival, and we proposed a new staging system by combining IB and IIA and stratifying all patients with high CA19-9 into stage III. The modified staging system had a better performance for predicting CSS than the 8th AJCC staging scheme.ConclusionsThe 8th AJCC staging system for PDAC is suitable for a Chinese cohort of resected patients, and the N category has a better prognostic value than the T category. Our modified staging system has superior accuracy in predicting survival than the 8th AJCC TNM staging system.

Duodenal/ampullary invasion is a poor prognostic factor for neoadjuvant-treated pancreatic ductal adenocarcinoma patients

Presenter: Katelyn Smith BA | University of Pittsburgh Medical Center Background: The current 8th edition of the American Joint Committee on Cancer (AJCC) T-staging system for pancreatic ductal adenocarcinoma (PDAC) is largely based on tumor size. In contrast, previous editions have not only incorporated tumor size but have also included extrapancreatic extension of the primary tumor. This modification in T-staging was done in part to address concerns of pathologic reproducibility in defining tumor spread into the surrounding peripancreatic soft tissue. While removing extrapancreatic extension may facilitate a more reproducible system, relying on tumor size alone may not account for other prognostic and less contentious pathologic features, such as duodenal/ampullary invasion. Moreover, considering the recent shift in clinical practice to include neoadjuvant therapy, defining and validating prognostic parameters for posttherapy pancreatectomy specimens are imperative. Methods: The prevalence and clinicopathologic features associated with PDAC invasion into the duodenum/ampulla were evaluated for 341 treatment-naïve patients and 329 neoadjuvant-treated patients between 2006 to 2016. These findings were separately analyzed using a cohort of 161 neoadjuvant-treated patients that were obtained between 2017 to 2019. Kaplan-Meier survival estimates and Cox proportion hazard regression were performed to identify predictors of overall survival (OS). Results: In comparison to treatment-naïve patients, neoadjuvant-treated patients had a lower prevalence of duodenal/ampullary involvement (44% vs. 57%, p = 0.002). A cross-comparison between treatment cohorts for patients without carcinomatous spread to the duodenum/ampulla revealed neoadjuvant-treated patients harbored smaller tumors (2.4 cm vs. 2.9 cm, p < 0.001) and had a lower prevalence of both perineural invasion (70% vs. 88%, p < 0.001) and lymphovascular invasion (60% vs. 75%, p = 0.005) as compared to treatment-naïve patients. A similar relationship was not observed between treatment groups for patients with duodenal/ampullary invasion and suggests duodenal/ampullary invasion may be an indicator of neoadjuvant treatment resistance. In the setting of neoadjuvant therapy, the detection of duodenal/ampullary involvement in posttherapy specimens correlated with a decreased 3-year OS rate (22% vs. 35%, p = 0.001), while no association between duodenal/ampullary invasion and OS was seen for treatment-naïve patients. A shorter OS for duodenal/ampullary invasion was also identified using a separate validation cohort of 161 neoadjuvant-treated patients (35% vs. 46%, p = 0.010). Among a total of 490 patients receiving neoadjuvant therapy, tumor infiltration into the duodenum/ampulla was a negative prognostic factor for poor OS (p = 0.042) by multivariate analysis (Table). Conclusion: The identification of duodenal/ampullary invasion in neoadjuvant-treated patients correlates with decreased patient OS and may reflect resistance to neoadjuvant therapy. Additionally, tumor infiltration into the duodenum/ampulla is a prognostic indicator for poor patient OS and is independent of other known prognostic parameters, such as the AJCC 8th edition T-staging system. Thus, the inclusion of duodenal/ampullary invasion in future editions of the AJCC T-staging system for neoadjuvant-treated patients may be of value.

Sex-specific survival benefit in early skin melanoma based on 8th AJCC edition: an analysis of data from the Surveillance, Epidemiology, and End Results (SEER) database.

BackgroundFemales have been found to have a survival benefit over males in past studies. However, in early melanoma patients, this benefit occurred in only those aged >60 years. The 8th edition of the American Joint Committee on Cancer (AJCC) readjusted the melanoma staging system, specifically stage I. This study aims to verify whether the sex-specific benefit in females exists in different age groups according to the 8th edition of the staging system.MethodsWe collected the data of individuals diagnosed with skin melanoma between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Based on the 8th edition of the melanoma staging system, patients diagnosed with pathological stage T1a-T3a, N0 and M0 melanoma were enrolled.ResultsA total of 115,576 patients, including 62,938 male patients and 52,638 female patients, were enrolled in this study. The survival rates of males and females in each stage from IA–IIA were significantly different (P<0.001). In further analyses of each age group, it was found that the proportions of patients with stages IA, IB and IIA were significantly different in each age group. Cox analysis showed that females with stage IA in all age groups benefited significantly, but those in stage IB benefited only when they were aged >60 years. In stage IIA patients, there were significant differences between the <50 and 61–70 years age groups.ConclusionsBased on data from the SEER database, we found that according to the 8th edition of the AJCC melanoma staging system, females had a higher survival rate than males, and this difference was significant in all age groups in the stage IA group but fluctuated with age in the stage IB and IIA groups.

Postresection prognosis of combined hepatocellular carcinoma-cholangiocarcinoma according to the 2010 World Health Organization classification: single-center experience of 168 patients.

PurposeCombined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) has wide histologic diversity. This study investigated the effects of cHCC-CC histology, according to the 2010 World Health Organization (WHO) classification, on patient prognosis.MethodsThe medical records of patients who underwent surgical resection for cHCC-CC at our institution between July 2012 and June 2019 were retrospectively evaluated.ResultsDuring the study period, 168 patients, 122 males (72.6%) and 46 females (27.4%), underwent surgical resection for cHCC-CC, including 159 patients (94.6%) who underwent R0 resection. Mean tumor diameter was 4.4 ± 2.8 cm, and 161 patients (95.8%) had solitary tumors. Histologically, 86 patients (51.2%) had classical type, and 82 (48.8%) had tumors with stem cell (SC) features, including 33 (19.6%) with intermediate-cell and 23 (13.7%) each with typical SC and cholangiolocellular features; 3 tumors (1.8%) were unclassifiable. At 1, 3, and 5 years, tumor recurrence rates were 31.9%, 49.6%, and 58.1%, respectively, and patient survival rates were 91.0%, 70.2%, and 60.3%, respectively. Univariate analysis showed that tumor size of >5 cm, microscopic and macroscopic vascular invasion, lymph node metastasis, 8th edition of the American Joint Committee on Cancer (AJCC) tumor stage, and 2010 WHO classification were significantly prognostic. Multivariate analysis showed that the 8th AJCC tumor stage and 2010 WHO histologic classification were independently prognostic for tumor recurrence and patient survival. There were no significant prognostic differences among the 3 SC subtypes.ConclusionPostresection outcomes are better in patients with SC-type than with classical-type cHCC-CC.

Prognostic and Predictive Value of the American Joint Committee on Cancer Pathological Prognostic Staging System in Nodal Micrometastatic Breast Cancer.

IntroductionTo investigate the prognostic and predictive effect of the American Joint Committee on Cancer (AJCC) 8th edition pathological prognostic staging system in patients with T1-2N1micM0 breast cancer who underwent mastectomy.MethodsData from T1-2N1micM0 breast cancer patients who underwent mastectomy from 2010–2014 were obtained from the Surveillance, Epidemiology, and End Results program. The chi-square test, binomial logistics regression, receiver-operating characteristics curve, competing-risk regression model, Cox proportional hazards regression model, and proportional hazard assumption were used for statistical analyses.ResultsWe identified 4,729 patients, including 1,062 patients were received postmastectomy radiotherapy (PMRT). Stage change occurred in 88.2% of the patients, of which 84.4% were downstaged and 3.7% were upstaged. Patients with higher pathological prognostic stages were independently predicted to receive PMRT. The 5-year breast cancer-specific survival (BCSS) was 97.5, 93.7, 90.1, 86.0, and 73.5% in disease stages IA, IB, IIA, IIB, and IIIA, respectively, according to the 8th edition criteria (P < 0.001). The AJCC 8th edition demonstrated moderate discriminative ability, and it had a significantly better ability to predict the BCSS than the AJCC 7th edition criteria (P < 0.001). The multivariate prognostic analysis showed that the new pathological prognostic staging was an independent prognostic factor affecting the BCSS. The BCSS worsened with an increase in the stage. The PMRT did not affect the BCSS regardless of the pathological prognostic stage. Similar trends were found using the competing-risks regression model.ConclusionsThe 8th AJCC breast cancer pathological prognostic staging system downstaged 84.4% of patients with T1-2N1micM0 disease and the survival outcome prediction with this staging system was more accurate than the AJCC 7th edition system. Our study does not support using the prognostic stage as a guideline to escalate of PMRT.

YpT0 gastric carcinoma after preoperative chemotherapy: a unique status according to AJCC 8th edition cancer staging system.

BackgroundAmerican Joint Committee on Cancer (AJCC) recently had published 8th edition staging system, in which a separate staging system was proposed for gastric cancers those received preoperative therapy (ypStage), however ypT0 was not included. The aim of this study was to propose the inclusion of ypT0 into the new staging classification.MethodsWe collected data of gastric cancer patients who underwent gastrectomy after preoperative chemotherapy in the First Affiliated Hospital of Zhejiang University (2004–2015). Kaplan-Meier survival estimations and log-rank tests were performed to compare survival.Results314 patients were enrolled in this study according to inclusion and exclusion criteria. The 5-year overall survival (OS) rate of all patients was 53.5% and the survival estimation was well discriminated by ypstage (P<0.001). Twenty-five patients were identified achieving pathological complete regression in primary lesion (ypT0), in which there were 16 pCR patients and 9 ypT0N+ patients. The 5-year OS of pCR patients was 93.8%, which was not better than ypstage I with 5-year OS of 97.5% (P=0.507). Meanwhile, ypT0N+ patients’ 5-year OS was 66.7%, which was significantly shorter than those with ypstage I (P=0.002), but no statistical difference from ypstage II with 5-year OS of 71.6% (P=0.583).ConclusionsComplete pathological regression of primary lesion (ypT0) was a predictor for long-term outcomes. pCR and ypT0N+ patients might be considered for inclusion in the ypstage I and ypstage II group respectively.

Modification of the 8th American Joint Committee on Cancer staging system for gallbladder carcinoma to improve prognostic precision

BackgroundThe 8th edition of the American Joint Committee on Cancer (AJCC) staging system for gallbladder carcinoma (GBC) came into force since 2018. However, the prognostic precision of this staging system has not been properly assessed. This study aimed to evaluate the latest staging system and suggest modifications to improve its prognostic precision.MethodsData of patients with GBC was included from the Surveillance, Epidemiology and End Results (SEER) database (2004–2015) and multicenter database (2010–2017). Baseline clinicopathologic characteristics were recorded including age, sex, race, grade, T category, N category, M category and stage. The Kaplan-Meier method was used to plot survival functions. The prediction power of the AJCC 8th edition and its modified version were evaluated using the concordance index (C-index).ResultsA total of 2779 GBC patients were included in the SEER database and 591 were collected from multicenter database. While no significant difference in survival of patients was observed between stages IVA and IVB using the 8th AJCC staging system (p > 0.05), the prognosis of stage IIIA showed a slightly better outcome than stage IIIB (p = 0.046) in the SEER database. In the multicenter database, there was no significant difference between stage IIIA and stage IIIB (p > 0.05). Similarly, no significant difference in the survival of patients between stages IIIA and IIIB was observed when M0 patients with at least 6 lymph nodes (LNs) were analyzed (p > 0.05) for both SEER and multicenter database. On the other hand, a modified staging system was able to stratify patients from stage IIIA, stage IIIB and stage IV (p < 0.001). For the SEER database, the C-indexes of 8th AJCC staging system and that of its modified version were 0.709 and 0.742, respectively. For the multicenter database, the C-index of 8th AJCC staging system and that of our modified version were 0.635 and 0.679, respectively.ConclusionsThe modified 8th staging system proposed in this study can improve the prognostic precision of the 8th AJCC staging system for GBC. We therefore suggest including these modifications in the next update of AJCC staging system for GBC.

A comprehensive validation of the novel 8th edition of American Joint Committee on Cancer staging manual for the long-term survivals of patients with non-functional pancreatic neuroendocrine neoplasms.

Histologically, the World Health Organization has classified pancreatic neuroendocrine neoplasms (p-NENs) into well-differentiated pancreatic neuroendocrine tumors (G1/G2 p-NETs) and poorly-differentiated pancreatic neuroendocrine carcinoma (G3 p-NECs) based on tumor mitotic counts and Ki-67 index. Recently, the 8th edition of American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging manual has incorporated some major changes in 2017 that the TNM staging system for p-NENs should only be applied to well-differentiated G1/G2 p-NETs, while poorly-differentiated G3 p-NECs be classified according to the new system for pancreatic exocrine adenocarcinomas. However, this new manual for p-NENs has seldom been evaluated.Data of patients with both G1/G2 and G3 non-functional p-NENs (NF-p-NENs) from our institution was retrospectively collected and analyzed using 2 new AJCC 8th staging systems. We also made survival comparisons between the 8th and 7th edition system separately for different subgroups.For G1/G2 NF-p-NETs, there were 52 patients classified in AJCC 8th edition stage I, 40 in stage II, 41 in stage III and 19 in stage IV. As for G3 NF-p-NECs, 17, 19, 24, and 18 patients were respectively defined from AJCC 8th edition stage I to stage IV. In terms of the AJCC 7th staging system, the 230 patients with NF-p-NENs were totally distributed from stage I to stage IV (94, 63, 36, 37, respectively). For the survival analysis of both G1/G2 NF-p-NETs and G3 NF-p-NECs, the AJCC 7th edition system failed to discriminate the survival differences when compared stage III with stage II or stage IV (P > .05), while the 8th edition ones could perfectly allocate patients into 4 statistically different groups (P < .05). The HCIs of AJCC 8th stage for G1/G2 NF-p-NETs [HCI=0.658, 95% confidence interval (CI)=0.602-0.741] and stage for G3 NF-p-NECs (HCI=0.704, 95% CI=0.595-0.813) was both statistically larger than those of AJCC 7th stage for different grading NF-p-NENs [(HCI=0.578, 95% CI=0.557-0.649; P=.031), (HCI=0.546, 95% CI=0.531-0.636; P = .019); respectively], indicating a more accurate predictive ability for the survivals of NF-p-NENs.Our data suggested the 2 new AJCC 8th staging systems were superior to its 7th edition for patients with both G1/G2 NF-p-NETs and G3 NF-p-NECs.

Prognostic Values of Preoperative Inflammatory and Nutritional Markers for Colorectal Cancer.

BackgroundIncreasing evidence indicates that inflammation and nutritional status are associated with survival outcomes in patients with colorectal cancer (CRC). This study aimed to investigate the prognostic values of preoperative inflammatory and nutritional factors and develop a prognostic model individually predicting overall survival (OS) and disease-free survival (DFS) in patients with CRC.MethodsWe retrospectively collected data on patients with CRC who underwent radical surgery. Independent prognostic inflammatory and nutritional markers were identified and novel prognostic models were developed incorporating the identified factors. The discriminative ability and model-fitting performance were evaluated by receiver operating characteristic curves and Akaike information criteria. Clinical usefulness was assessed by decision curve analysis.ResultsA total of 400 eligible patients were identified. Multivariate analysis identified pN stage, tumor differentiation grade, neutrophil count, and body mass index as independent prognostic factors for OS, and pN stage, tumor differentiation grade, neutrophil count, neutrophil-lymphocyte ratio, and serum albumin as prognostic factors for DFS. The combined inflammatory and nutritional prognostic model showed better discriminative ability, model-fitting performance, and net benefits than the inflammatory and nutritional models alone, and the American Joint Committee on Cancer (AJCC) 8th TNM classification for predicting OS and DFS.ConclusionPreoperative nutritional and inflammatory factors have significant prognostic value in patients with CRC. A novel prognostic model incorporating preoperative inflammatory and nutritional markers provides better prognostic performance than the AJCC 8th TNM classification. A novel nomogram incorporating preoperative inflammatory and nutritional markers can individually predict OS and DFS in patients with CRC.

Reappraisal of the T Category for Solitary Intrahepatic Cholangiocarcinoma by Tumor Size in 611 Early-Stage (T1-2N0M0) Patients After Hepatectomy: a Surveillance, Epidemiology, and End Results (SEER) Analysis

BackgroundThe association between tumor size and survival in patients with intrahepatic cholangiocarcinoma (ICC) after hepatectomy is controversial, and the T category in the American Joint Committee on Cancer (AJCC) stage for ICC is a topic of debate. MethodsData from 611 T1-2N0M0 ICC patients classified by the AJCC 8th edition who underwent hepatectomy were extracted from the Surveillance, Epidemiology, and End Results (SEER) database during 1988–2015. Cancer-specific survival was evaluated using Kaplan-Meier analysis. The optimal cutoff value of solitary tumor size was used an adjusted p value approach to discriminating patient survival. ResultsIn the AJCC 8th staging system, using a 5-cm cut-off value of tumor size for solitary ICC without vascular invasion (S/VI–) was not associated with survival in T1 category (p = 0.201), and multifocal ICC with vascular invasion had a worse survival than solitary ICC with vascular invasion (S/VI+) in T2 category (p = 0.014). Tumor size was a prognostic factor for both S/VI– and S/VI+, the optimal cutoff value of tumor size was obtained 8 cm for S/VI– and 3 cm for S/VI+. S/VI– ≤ 8 cm had a similar survival to S/VI+ ≤ 3 cm (p = 0.126), S/VI– > 8 cm had a similar survival to S/VI+ > 3 cm (p = 0.655), and multifocal ICC had a similar survival with S/VI– > 8 cm (p = 0.159) and S/VI+ > 3 cm (p = 0.196). When the cohort was divided into two groups—new T1 (S/VI– ≤ 8 cm and S/VI+ ≤ 3 cm) and new T2 (S/VI– > 8 cm, S/VI+ > 3 cm and multifocal ICC)—significant survival difference was observed (p < 0.0001). ConclusionsThe discriminatory power of the AJCC 8th edition for solitary ICC could be further enhanced by subdividing tumors according to size and vascular invasion (8 cm for S/VI– and 3 cm for S/VI+).

A 45-year experience of uveal melanoma in Taiwan: Verification of American Joint Committee on Cancer staging system and prognostic factors

To verify the staging system of the American Joint Committee on Cancer (AJCC) 8th edition for uveal melanoma, and to propose the prognostic factors of uveal melanoma by a 45-year cohort study. We collected patients who underwent operation with pathological proof from 1973 to 2017. The demographic data including gender, age, laterality, metastatic pattern, and histopathology type were recorded. The predictability for survival and monotonicity of gradients of the AJCC 8th edition were evaluated. The prognostic factors for survival were analyzed by univariate and multivariate analysis. A total of 72 patients were collected. The median age was 55 year-old (range 24-100). No specific gender predilection was revealed in our study. About 75.9% of metastases events happened in the first five-year of follow-up, and hepatic involvement was the most common. By the AJCC 8th edition, the distribution for stage I: II: III was 8 (11.1%), 37 (51.4%), and 27 (37.5%). The prognostic staging groups manifested fair predictability and monotonicity of gradients for survival outcome. The tumors with epithelioid cell type and ciliary body involvements had higher tumor-related mortality. The AJCC 8th edition prognostic staging groups for outcome prediction was validated. Periodic screening for metastases should be more frequent in the first five-year follow-up. The tumors with epithelioid cell pattern and ciliary body involvements were at risk of higher tumor-related mortality in Taiwanese patients.

National, Observational, Multicentric Retrospective Study to Understand Treatment Patterns, Patient Journey and Characteristics with Stage III Non-Small Cell Lung Cancer Patients in Turkey: Stone Trial

In this multi-institutional study, we sought to investigate the contemporary treatment patterns of patients at initial and during first and second progression diagnosed with primary stage III NSCLC in Turkey. The patient characteristics, disease burden, treatment patterns and patient journey of stage III NSCLC patients were revealed. The clinical data of 492 patients treated between 2013 and 2017 were collected from geographically diverse set of ten community oncology centers in Turkey. The initial treatment included all treatment facilities after diagnosis. It includes chemotherapy (ChT) and radiotherapy (RT) delivered either sequentially or concurrently. These treatment patterns are analyzed at first treatment period, and during first and second progression periods. Median age was 64 years (range, 40 – 90 years). Most of the patients were male (434 patients, 88.2%) and were either past smoker or current smoker (462 patients, 93.9%). More than half of the patients (56.1%) had squamous cell carcinoma (SCC) and mean tumor size was 5.1±2.1 cm. According to the American Joint Committee on Cancer (AJCC) staging system 7th edition clinical stage IIIA (311 patients, 63.2%) was more frequently seen, and stage IIIB (278 patients, 56.5%) was most frequent when patients were staged according to AJCC 8th edition. For initial treatment 429 patients (89.2%) received ChT and RT, either concurrently (393 patients, 79.9%) or sequentially (46 patients, 9.3%), and only 53 patients (10.8%) were treated with RT only. Most frequently used RT technique was 3-dimensional conformal RT (3DCRT) (276 patients, 56.0%), while only 3 patients (0.6%) were treated with stereotactic radiotherapy (SBRT). Median 9.3 months after completion of initial treatment 288 patients (58.4%) had disease progression, and 166 patients (64.6%) received treatment). The main treatment modality at first progression was systemic treatment (121 patients, 72.9%), while 65 patients (37.1%) were treated with RT only. The RT treatment sites were mostly to the metastatic sites. The SBRT technique was used in 25 patients (22.2%). Disease progression was observed in 30 patients median 4.2 months (range, 0.8 – 11.4 months) after completion of treatment of first progression. Of these patients 20 patients (66.7%) received systemic therapy. The use of TKI and immunotherapeutic agent was quite limited in this cohort during initial treatment, first and second progression time. In the initial treatment period, none of the patients received TKI and immunotherapy. Only 7 patients (5.8%) received TKI and 3 patients (2.5%) had immunotherapeutics during first progression interval. At second progression only 2 patients (1%) received TKI and immunotherapy separately. This national observational study showed that the majority of patients with unresectable stage III NSCLC received cCRT as the first therapy, and this practice was consistent with guidelines.

Development and Validation of a Clinical Prognostic Stage Group System for Nonmetastatic Prostate Cancer Using Disease-Specific Mortality Results From the International Staging Collaboration for Cancer of the Prostate

In 2016, the American Joint Committee on Cancer (AJCC) established criteria to evaluate prediction models for staging. No localized prostate cancer models were endorsed by the Precision Medicine Core committee, and 8th edition staging was based on expert consensus. To develop and validate a pretreatment clinical prognostic stage group system for nonmetastatic prostate cancer. This multinational cohort study included 7 centers from the United States, Canada, and Europe, the Shared Equal Access Regional Cancer Hospital (SEARCH) Veterans Affairs Medical Centers collaborative (5 centers), and the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry (43 centers) (the STAR-CAP cohort). Patients with cT1-4N0-1M0 prostate adenocarcinoma treated from January 1, 1992, to December 31, 2013 (follow-up completed December 31, 2017). The STAR-CAP cohort was randomly divided into training and validation data sets; statisticians were blinded to the validation data until the model was locked. A Surveillance, Epidemiology, and End Results (SEER) cohort was used as a second validation set. Analysis was performed from January 1, 2018, to November 30, 2019. Curative intent radical prostatectomy (RP) or radiotherapy with or without androgen deprivation therapy. Prostate cancer-specific mortality (PCSM). Based on a competing-risk regression model, a points-based Score staging system was developed. Model discrimination (C index), calibration, and overall performance were assessed in the validation cohorts. Of 19 684 patients included in the analysis (median age, 64.0 [interquartile range (IQR), 59.0-70.0] years), 12 421 were treated with RP and 7263 with radiotherapy. Median follow-up was 71.8 (IQR, 34.3-124.3) months; 4078 (20.7%) were followed up for at least 10 years. Age, T category, N category, Gleason grade, pretreatment serum prostate-specific antigen level, and the percentage of positive core biopsy results among biopsies performed were included as variables. In the validation set, predicted 10-year PCSM for the 9 Score groups ranged from 0.3% to 40.0%. The 10-year C index (0.796; 95% CI, 0.760-0.828) exceeded that of the AJCC 8th edition (0.757; 95% CI, 0.719-0.792), which was improved across age, race, and treatment modality and within the SEER validation cohort. The Score system performed similarly to individualized random survival forest and interaction models and outperformed National Comprehensive Cancer Network (NCCN) and Cancer of the Prostate Risk Assessment (CAPRA) risk grouping 3- and 4-tier classification systems (10-year C index for NCCN 3-tier, 0.729; for NCCN 4-tier, 0.746; for Score, 0.794) as well as CAPRA (10-year C index for CAPRA, 0.760; for Score, 0.782). Using a large, diverse international cohort treated with standard curative treatment options, a proposed AJCC-compliant clinical prognostic stage group system for prostate cancer has been developed. This system may allow consistency of reporting and interpretation of results and clinical trial design.

Clinical Utility of ypTNM Stage Grouping in the 8th Edition of the American Joint Committee on Cancer TNM Staging System for Esophageal Squamous Cell Carcinoma

The 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system provided a specific 'ypTNM' stage grouping for patients with esophageal cancer. This study aimed to evaluate the clinical utility of the AJCC 8th edition ypTNM stage grouping for patients with esophageal squamous cell carcinoma (ESCC). We enrolled 152 patients with ESCC who underwent surgery after neoadjuvant cisplatin plus 5-fluorouracil (CF) therapy between June 2005 and December 2011. ypStage was evaluated according to the AJCC 7th and 8th editions. Predictive performance for disease-specific survival (DSS) and overall survival (OS) was compared between both editions. The prognostic significance of ypTNM stage grouping was evaluated using univariate and multivariate analyses. Revision of the AJCC 7th edition to the 8th edition was associated with a change in ypStage in 96 patients (63.2%). The AJCC 8th edition revealed a better predictive performance than the 7th edition in terms of DSS (Akaike's information criterion [AIC] 499 vs. 513; Bayesian information criterion [BIC] 505 versus 519; concordance index [C-index] 0.725 versus 0.679) and OS (AIC 662 vs. 674; BIC 669 vs. 681; C-index 0.662 vs. 0.622). On univariate and multivariate analyses, ypStage in the 8th edition was an independent prognostic factor for both DSS and OS. ypTNM stage grouping in the AJCC 8th edition provided a better predictive performance for DSS and OS than that in the 7th edition. ypStage in the 8th edition was the most reliable prognostic factor for ESCC patients who underwent surgery after neoadjuvant CF therapy.

Novel analysis of prognosis of young patients with stage II differentiated thyroid cancer based on AJCC 8.0 and 6.0 criteria to implement the staging system.

The incidence of thyroid cancer among young adults is increasing; however, the clinical challenges specific to this population, such as diagnosis, reduced healthcare access, and inconsistent care, have received limited attention. Here, we conducted a subgroup analysis on a series of relatively young patients with differentiated thyroid carcinomas (DTCs), focusing on those with distant metastases at stage II, to obtain a deeper understanding of the factors influencing survival. Information on <45- or <55-year-old patients at any T/N stage with distant metastasis (M1) was extracted from the SEER database according to the staging system in the 6th and 8th American Joint Committee on Cancer (AJCC) editions, respectively. Patient mortality was evaluated using Cox proportional hazards regression analyses and Kaplan-Meier analyses with log-rank tests. Both cancer-specific and all-cause mortality rates per 1,000 person-years for patients ≥35 years old significantly differed from those of patients <35 years old. DTC-specific survival curves also significantly differed between these age groups, according to both the AJCC 6.0 and 8.0-based analyses (P=0.0017 and P<0.001, respectively), as did patient survival curves (P=0.0003, P<0.001, respectively). The multivariate Cox regression model also revealed that poor OS was strongly predicted by race (P<0.001) in the analysis based on the criteria of 8th AJCC staging system. Age is a risk factor for disease-specific and overall survival (OS) in young patients with stage II DTC, and young male patients exhibited poorer survival than females. Race also emerged as a potential risk factor for young patients in stage II. These findings offer guidance for improving the older and newer versions of the AJCC staging system.

Prognostic Relevance of the Eighth Edition of TNM Classification for Resected Perihilar Cholangiocarcinoma.

Objectives: In our study, we evaluated and compared the prognostic value and performance of the 6th, 7th, and 8th editions of the American Joint Committee on Cancer (AJCC) staging system in patients undergoing surgery for perihilar cholangiocarcinoma (PHC). Methods: Patients undergoing liver surgery with curative intention for PHC between 2002 and 2019 were identified from a prospective database. Histopathological parameters and stage of the PHC were assessed according to the 6th, 7th, and 8th editions of the tumor node metastasis (TNM) classification. The prognostic accuracy between staging systems was compared using the area under the receiver operating characteristic curve (AUC) model. Results: Data for a total of 95 patients undergoing liver resection for PHC were analyzed. The median overall survival time was 21 months (95% CI 8.1–33.9), and the three- and five-year survival rates were 46.1% and 36.2%, respectively. Staging according to the 8th edition vs. the 7th edition resulted in the reclassification of 25 patients (26.3%). The log-rank p-values for the 7th and 8th editions were highly statistically significant (p ≤ 0.01) compared to the 6th edition (p = 0.035). The AJCC 8th edition staging system showed a trend to better discrimination, with an AUC of 0.69 (95% CI: 0.52–0.84) compared to 0.61 (95% CI: 0.51–0.73) for the 7th edition. Multivariate survival analysis revealed male gender, age >65 years, positive resection margins, presence of distant metastases, poorly tumor differentiation, and lymph node involvement, such as no caudate lobe resection, as independent predictors of poor survival (p < 0.05). Conclusions: In the current study, the newly released 8th edition of AJCC staging system showed no significant benefit compared to the previous 7th edition in predicting the prognosis of patients undergoing liver resection for perihilar cholangiocarcinoma. Further research may help to improve the prognostic value of the AJCC staging system for PHC—for instance, by identifying new prognostic markers or staging criteria, which may improve that individual patient’s outcome.

Lymph Node Ratio-Based Staging System for Gallbladder Cancer With Fewer Than Six Lymph Nodes Examined

PurposeThe 8th edition of the American Joint Committee on Cancer (AJCC) tumor-lymph node-metastasis (TNM) staging system for gallbladder cancer (GBC) recommended that at least six lymph nodes (LNs) should be examined. But most patients with GBC had fewer than six LNs resected. This study aimed to establish an alternative index for assessing the LN status during the staging system for GBC patients with fewer than six LNs retrieved.Patients and MethodsPatient data was extracted from the Surveillance, Epidemiology, and End Results (SEER) database (cases between 2004 and 2013). X-tile software was used to determine the optimal cutoff value for lymph node ratio (LNR) and a concordance index (C-index) was used to evaluate the discriminatory powers of the two staging systems.ResultsThe majority of GBC patients in our cohort (1353, 78.5%) had fewer than six LNs examined. Among patients with inadequate LN examination, the higher number of LNs examined correlated with a lower proportion of patients. Using the TNM staging system, the C-index for patients with fewer than six LNs and patients with six or more LNs screened were 0.636 and 0.704, respectively. Using the staging system based on LNR (TNrM), the C-index for patients with fewer than six LNs retrieved and patients with six or more LNs retrieved were 0.649 and 0.694, respectively. Similar results were observed in patients with gallbladder adenocarcinoma (GBA).ConclusionTNrM might be superior to the 8th AJCC TNM staging system for stratifying GBC patients with fewer than six LNs examined, and it can complement TNM for more accurate risk stratification. Future prospective studies are needed to validate our findings.

Equipping the American Joint Committee on Cancer Staging for Resectable Pancreatic Ductal Adenocarcinoma with Tumor Grade: A Novel Staging System.

Background The 8th American Joint Committee on Cancer (AJCC) staging system for pancreatic ductal adenocarcinoma (PDAC) outperforms its previous version in reproducibility but not in survival discrimination. Tumor grade, an indicator of the aggressive biology of PDAC, has been suggested as a reliable prognostic factor. This study aimed to construct a novel staging system with greater prognostication for resectable PDAC by incorporating tumor grade into the 8th AJCC system. Methods A total of 9966 patients with resectable PDAC from the Surveillance Epidemiology and End Results (SEER) database were randomly separated into training and interval validation sets. Another 324 patients from our center were included as an external validation set. We proposed a novel staging system by sorting the substages yielded by a combination of T, N, and tumor grade based on their overall survival (OS) and grouping them into several stages. Prognostic homogeneity and discrimination were determined using the likelihood ratio χ2 and the linear trend χ2 test, respectively. Prognostic accuracies were evaluated by the area under the receiver operating characteristics curve (AUC). Results Using the 8th AJCC system, the prognosis of patients within the same stage was quite heterogeneous among different substages. The multivariate Cox model identified the tumor grade (hazard ratio 1.333, 95% confidence interval 1.250–1.423, p < 0.001) was an independent prognostic factor of the OS. In the training set, the AUC, homogeneity, and discriminatory ability were superior for the novel staging system than for the 8th AJCC system (0.642 vs. 0.615, 403.4 vs. 248.6, and 335.1 vs. 218.0, respectively). Similar results were observed in the internal and external validation sets. Conclusions The novel staging system incorporating tumor grade into the 8th AJCC system was associated with better prognostic accuracy, homogeneity, and discriminatory ability among resectable PDAC patients. Moreover, the novel staging system also allowed possibly adjuvant chemotherapy decisions.