American Joint Committee On Cancer Eighth Edition Research Articles

Application of the Eighth Edition of the American Joint Committee on Cancer Staging for Pancreatic Adenocarcinoma.

Notable modifications have been made in the American Joint Committee on Cancer (AJCC) Staging eighth edition staging for pancreatic cancer for the consideration of the irreproducible and inapplicable of the AJCC seventh edition staging. However, the new staging classification has not been systemically verified. A comparison was performed to evaluate the application of the AJCC seventh and eighth staging classifications using the Surveillance, Epidemiology, and End Results registry (18,450 patients) and an institutional series (2040 patients). For the eighth staging classification, patients with tumor diameter of greater than 4 cm (T3N0M0, IIA) had similar prognosis to patients with 1 to 3 positive nodes (T1-3N1M0, IIB). For patients who underwent tumor resection and without lymph node involvement, survival curves of T1 (≤2 cm), T2 (2-4 cm), and T3 (>4 cm) were well separated. Statistical difference in survival analyses was demonstrated in N0 (0 positive node), N1 (1-3 positive nodes), and N2 (≥4 positive nodes) patients underwent tumor resection. The AJCC eighth edition had better stage distribution than the AJCC seventh edition for pancreatic cancer. The eighth edition of AJCC staging is more applicable and accurate than the seventh edition for pancreatic adenocarcinoma.

Ocular surface squamous neoplasia: analysis based on the 8th American Joint Committee on Cancer classification.

To evaluate outcomes of ocular surface squamous neoplasia (OSSN) based on American Joint Committee on Cancer (AJCC), 8th edition classification. Retrospective, non-randomized interventional case series of 127 patients (136 eyes) with OSSN. On the basis of the AJCC (eighth edition), OSSN was classified as per T category as Tis (n = 14, 10%), T1 (n = 0), T2 (n = 4, 3%), T3 (n = 113, 83%), and T4 (n = 5, 4%). The following parameters increased with increasing T category: mean age at presentation at 37years for Tis, 43years for T2, 46years for T3, and 55years for T4 (p = 0.04); mean tumor basal diameter of 4mm for Tis, not applicable (na) for T1, 6mm for T2, 7mm for T3, 20mm for T4 (p = 0.001); extent of clock hours of corneal involvement (0, na, 0, 4, 8; p = 0.02), and conjunctival involvement (1, na, 2, 3, 9; p = 0.0005); involvement of adjacent structures including fornix (0%, na, 0, 9, 80%; p < 0.001), and caruncle (0%, na, 0, 3, 60%; p < 0.001) for Tis, T1, T2, T3, and T4, respectively. Overall, of the 136 eyes, 19 (14%) had tumor recurrence, and all tumor recurrences were seen in T3. Regional lymph node metastasis was noted in 4 (3%) patients. No systemic metastasis or death occurred in any patient during the mean follow-up period of 15months (median, 11months; range 6-55months). Increasing T category based on AJCC 8th edition classification is associated with increasing severity of disease, tumor recurrence rate, and the rate of regional lymph node metastasis.

Major prognostic factors for recurrence and survival independent of the American Joint Committee on Cancer eighth edition staging system in patients with cutaneous squamous cell carcinoma treated with multimodality therapy

The purpose of this study was to assess changes resulting from the American Joint Committee on Cancer (AJCC) eighth edition for cutaneous squamous cell carcinoma (SCC) and evaluate pertinent excluded factors. In 101 patients receiving surgery and postoperative radiation, recurrence and survival were estimated by cumulative incidence and Kaplan-Meier method. Time-to-event analysis was performed using Cox proportional hazards and Fine-Gray competing risks regression models. The 2-year locoregional recurrence, overall survival (OS), and cause-specific mortality rates were 25%, 72%, and 13%, respectively. The AJCC eighth edition upstaged T classification in 50% of patients and overall stage in 39%. In multivariate analysis, immunosuppression and in-transit metastasis were associated with locoregional recurrence. Older age and in-transit metastasis were associated with worse OS. In univariate analysis (limited by number of events), cause-specific mortality was associated with positive margin, in-transit metastasis, and the seventh edition dichotomized T classification and overall stage. In-transit metastasis was significantly associated with locoregional recurrence, OS, and cause-specific mortality. Efforts should be made to define in-transit metastasis in the staging system.

Validation of the Eighth American Joint Committee on Cancer Staging System for Distal Bile Duct Carcinoma.

PurposeT category of the eighth edition of the American Joint Committee on Cancer (AJCC) staging system for distal bile duct carcinoma (DBDC) was changed to include tumor invasion depth measurement, while the N category adopted a 3-tier classification system based on the number of metastatic nodes.Materials and MethodsTo validate cancer staging, a total of 200 surgically resected DBDCs were staged and compared according to the seventh and eighth editions.ResultsT categories included T1 (n=37, 18.5%), T2 (n=114, 57.0%), and T3 (n=49, 24.5%). N categories included N0 (n=133, 66.5%), N1 (n=50, 25.0%), and N2 (n=17, 8.5%). Stage groupings included I (n=33, 16.5%), II (n=150, 75.0%), and III (n=17, 8.5%). The overall 5-year survival rates (5-YSRs) of T1, T2, and T3 were 59.3%, 42.4%, and 12.2%, respectively. T category could discriminate patient survival by both pairwise (T1 and T2, p=0.011; T2 and T3, p < 0.001) and overall (p < 0.001) comparisons. The overall 5-YSRs of N0, N1, and N2 were 47.3%, 17.0%, and 14.7%, respectively. N category could partly discriminate patient survival by both pairwise (N0 and N1, p < 0.001; N1 and N2, p=0.579) and overall (p < 0.001) comparisons. The overall 5-YSRs of stages I, II, and III were 59.0%, 35.4%, and 14.7%, respectively. Stages could distinguish patient survival by both pairwise (I and II, p=0.002; II and III, p=0.015) and overall (p < 0.001) comparisons. On multivariate analyses, T and N categories (p=0.014 and p=0.029) and pancreatic invasion (p=0.006) remained significant prognostic factors.ConclusionThe T andNcategories of the eighth edition AJCC staging system for DBDC accurately predict patient prognosis.

Iris Melanoma Outcomes Based on the American Joint Committee on Cancer Classification (Eighth Edition) in 432 Patients

The American Joint Committee on Cancer (AJCC) classification was updated to the eighth edition in January 2017, providing staging for iris melanoma. This study evaluated outcomes of iris melanoma per the AJCC classification, eighth edition. Retrospective case series. Four hundred thirty-two patients with iris melanoma. Management including tumor resection, plaque radiotherapy, or enucleation. Local tumor recurrence, melanoma-related systemic metastasis, and melanoma-related death. Of 432 patients with iris melanoma, AJCC classification was category T1 (n= 324 [75%]), T2 (n= 83 [19%]), T3 (n= 2 [<1%]), and T4 (n= 23 [5%]). There was no difference in age, race, gender, eye, or iris color among T categories. Overall, Kaplan-Meier analysis of outcomes (at 5 and 10 years) revealed visual acuity reduction by 3 lines or more (42% and 54%, respectively), secondary glaucoma (29% and 33%, respectively), local recurrence (8% and 17%, respectively), secondary enucleation (12% and 19%, respectively), lymph node metastasis (1% and 1%, respectively), melanoma-related systemic metastasis (5% and 10%, respectively), and melanoma-related death (3% and 4%, respectively). Compared with T1 category, the hazard ratio (HR) for local recurrence in nonenucleated eyes was 1.31 for T2, not evaluable (NE) for T3 (because of small cohort), and 6.61 for T4; the HR for metastasis was 3.41 for T2, NE for T3 (because of small cohort), and 25.6 for T4; the HR for death was 7.51 for T2, NE for T3 (because of small cohort), and 26.5 for T4; and the odds ratio for enucleation was 1.23 for T2, 3.63 for T3, and 4.72 for T4. Features predictive of melanoma-related metastasis (multivariate analysis) included secondary glaucoma (P < 0.001; HR, 4.51), T2 category (vs. T1; P= 0.01; HR, 4.09), and T4 category (vs. T1; P < 0.001; HR, 30.8). Features predictive of melanoma-related death (multivariate analysis) included older age (P= 0.008; HR, 2.16 per 10-year increase), T2 category (vs. T1; P= 0.005; HR, 8.07), and T4category (vs. T1; P < 0.001; HR, 20.3). The AJCC eighth edition classification provides prognostic stratification of iris melanoma. By multivariate analysis, the ratio for melanoma-related metastasis was 4 times greater in category T2 and 31 times greater in T4 compared with T1. The ratio for melanoma-related death was 8 times greater in category T2 and 20 times greater in T4 compared with T1. The cohort size for T3 was too small to provide useful information.

Treatment deintensification in human papillomavirus-positive oropharynx cancer: Outcomes from the National Cancer Data Base.

The growing epidemic of human papillomavirus-positive (HPV+) oropharyngeal cancer and the favorable prognosis of this disease etiology have led to a call for deintensified treatment for some patients with HPV+ cancers. One of the proposed methods of treatment deintensification is the avoidance of chemotherapy concurrent with definitive/adjuvant radiotherapy. To the authors' knowledge, the safety of this form of treatment de-escalation is unknown and the current literature in this area is sparse. The authors investigated outcomes after various treatment combinations stratified by American Joint Committee on Cancer (AJCC) eighth edition disease stage using patients from the National Cancer Data Base. A retrospective study of 4443 patients with HPV+ oropharyngeal cancer in the National Cancer Data Base was conducted. Patients were stratified into AJCC eighth edition disease stage groups. Multivariate Cox regressions as well as univariate Kaplan-Meier analyses were conducted. For patients with stage I disease, treatment with definitive radiotherapy was associated with diminished survival compared with chemoradiotherapy (hazard ratio [HR], 1.798; P = .029), surgery with adjuvant radiotherapy (HR, 2.563; P = .002), or surgery with adjuvant chemoradiotherapy (HR, 2.427; P = .001). For patients with stage II disease, compared with treatment with chemoradiotherapy, patients treated with a single-modality (either surgery [HR, 2.539; P = .009] or radiotherapy [HR, 2.200; P = .030]) were found to have poorer survival. Among patients with stage III disease, triple-modality therapy was associated with improved survival (HR, 0.518; P = .024) compared with treatment with chemoradiotherapy. Deintensification of treatment from chemoradiotherapy to radiotherapy or surgery alone in cases of HPV+ AJCC eighth edition stage I or stage II disease may compromise patient safety. Treatment intensification to triple-modality therapy for patients with stage III disease may improve survival in this group. Cancer 2018;124:717-26. © 2017 American Cancer Society.

Validation Study of the American Joint Committee on Cancer Eighth Edition Prognostic Stage Compared With the Anatomic Stage in Breast Cancer

The American Joint Committee on Cancer (AJCC) eighth edition staging manual introduced a new prognostic stage for breast cancer incorporating biologic factors in addition to traditional anatomic factors. To perform a validation study of the AJCC eighth edition prognostic stage in a single-institution cohort and a large population database. Patients with breast cancer treated with surgery as an initial intervention were identified in a prospective institutional database from The University of Texas MD Anderson Cancer Center and the California Cancer Registry. Vital status data were complete through December 31, 2016, in The University of Texas MD Anderson cohort and through December 31, 2014, in the California Cancer Registry cohort. Patients receiving neoadjuvant systemic therapy, those with inflammatory or rare breast cancers, and those with unknown clinicopathologic factors were excluded. Factors evaluated included T, N, and M categories and tumor grade, as well as estrogen receptor, progesterone receptor, and HER2 status. Disease-specific survival was calculated by the Kaplan-Meier method. The Harrell concordance index (C index) was used to quantify models' predictive performance, and the Akaike information criterion (AIC) was used to compare model fits. A total of 3327 patients with stage I to IIIC breast cancer treated between 2007 and 2013 at The University of Texas MD Anderson Cancer Center (median follow-up of 5 years) with complete clinicopathologic data were identified. Compared with the AJCC anatomic stage, the prognostic stage upstaged 29.5% of patients and downstaged 28.1%. The prognostic stage (C index, 0.8357 and AIC, 816.8) provided more accurate stratification with respect to disease-specific survival than the anatomic stage (C index, 0.737 and AIC, 1039.8) (P < .001 for the C index). A total of 54 727 patients with stage I to IV breast cancer treated between 2005 and 2009 were identified in the California Cancer Registry (median follow-up of 7 years). The prognostic stage upstaged 31.0% of patients and downstaged 20.6%. The prognostic stage (C index, 0.8426 and AIC, 80 661.68) performed better than the anatomic stage (C index, 0.8097 and AIC, 81 577.89) (P < .001 for the C index). The prognostic stage provided more accurate prognostic information than the anatomic stage alone in both a single-institution cohort and a large population database, thereby supporting its use in breast cancer staging.

Validation of the American Joint Committee on Cancer eighth edition staging system in patients undergoing hepatectomy for hepatocellular carcinoma: a US population-based study

BackgroundThe American Joint Committee on Cancer (AJCC) eighth edition staging system for hepatocellular carcinoma (HCC) has incorporated several significant changes. This study aims to evaluate the newly proposed staging system and assess its strengths and weaknesses. Materials and methodsUsing the Surveillance, Epidemiology, and End Results database, we identified patients with pathologically confirmed stage I-III HCC diagnosed between 2004 and 2014. ResultsAfter all exclusion criteria were applied, AJCC seventh and eighth edition staging was possible in 4931 patients. According to the AJCC eighth edition staging system, stages IB and II did not differ significantly in terms of overall survival (OS) and cause-specific survival (CSS) (P = 0.928 and 0.872, respectively). On the basis of the above results, we reclassified T1a, T1b, and T2 into several subgroups. According to the modified AJCC eighth edition staging system, OS and CSS among the five groups of patients differed significantly. For OS predication, the Akaike information criterion values for the AJCC seventh, eighth, and modified eighth edition staging systems were 29,288.24, 29,282.85, and 27,182.21, respectively, and the c-indices for the AJCC seventh, eighth, and modified eighth edition staging systems were 0.5716, 0.5805, and 0.6082, respectively. Regarding CSS, the Akaike information criterion values for the AJCC seventh, eighth, and modified eighth edition staging systems were 21,701.11, 21,682.12, and 20,313.26, respectively, and the c-indices for the AJCC seventh, eighth, and modified eighth edition staging systems were 0.5983, 0.6117, and 0.6436, respectively. ConclusionsThis is the first large-scale validation of the AJCC eighth edition staging system for patients undergoing hepatectomy. Our study revealed that there was a lack of discrepancy in the outcomes for stage IB and II tumors for AJCC eighth edition staging system of HCC. Our modified AJCC eighth edition staging system allows for finer stratification of patients undergoing hepatectomy according to more detailed tumor size and vascular invasion classifications.

A Lymph Node Ratio-Based Staging Model Is Superior to the Current Staging System for Pancreatic Neuroendocrine Tumors.

The incidence of pancreatic neuroendocrine tumors (PNETs) is increasing. Current staging systems include nodal positivity, but the association of lymph node status and worse survival is controversial. The study aim was to determine the prognostic significance of lymph node ratio (LNR) and compare it with nodal positivity for PNET. A retrospective analysis of the Surveillance, Epidemiology, and End Results database between 2004 and 2011 was performed in patients who underwent a pancreatectomy with lymphadenectomy. The primary outcome was disease-specific survival (DSS). Of the 896 patients analyzed, T stage, N stage, distant metastasis, grade, extent of resection, sex, and age ≥57 years were significantly associated with worse DSS on univariate analysis. On multivariate analysis, age ≥57 [hazard ratio (HR) 1.75, 95% confidence interval (CI), 1.12 to 2.74, P = 0.015], male sex (HR 1.58; 95% CI, 1.01 to 2.48; P = 0.046), grade (poorly differentiated/undifferentiated: HR 7.59; 95% CI, 4.71 to 12.23; P < 0.001), distant metastases (HR 2.45; 95% CI, 1.58 to 3.79; P < 0.001), and partial pancreatectomy (HR 2.55; 95% CI, 1.2 to 5.4; P = 0.015) were associated with worse DSS. Comparison between staging models constructed based on LNR cutoffs and the American Joint Committee on Cancer (AJCC) eighth edition staging system revealed that a model based on LNR ≥0.5 was superior. LNR ≥0.5 is independently associated with worse DSS. A staging system with LNR ≥0.5 was superior to the current AJCC eighth edition staging system.

Interpretation and evaluation of the American Joint committee on Cancer (AJCC) 8th Edition Staging System for patients with gastroenteropancreatic neuroendocrine tumors

American Joint Committeeon Cancer (AJCC) released the eighth edition staging system manual in October 2016. Based on the shortcomings in the seventh edition of AJCC staging system, staging classifications for gastroenteropancreatic neuroendocrine tumor (GEP-NET) were updated. The changes are as follow: small intestinal NET was divided into two groups, duodenal and jejunoileal NET and lymphatic metastasis was redefined into N1 and N2 in jejunoileal NET; stages were condensed except colorectal NET; the staging classification for pancreatic NET proposed by European Neuroendocrine Tumor Society(ENETS) was adopted. However, problems still exist in the eighth edition AJCC staging classifications for GEP-NET. For instance, whether the definitions of N1 and N2 in jejunoileal NET are accurate in clinical management is still less understood. Thus, further clinical validations of the AJCC eighth edition staging system for GEP-NET are needed. Meanwhile, the eighth edition AJCC staging classifications for GEP-NET still did not step towards precision medicine and risks assessment models with high quality are still absent.

Next-Generation Sequencing: A Novel Approach to Distinguish Multifocal Primary Lung Adenocarcinomas from Intrapulmonary Metastases

Distinguishing between multiple lung primary tumors and intrapulmonary metastases is imperative for accurate staging. The American Joint Committee on Cancer (AJCC) criteria are routinely used for this purpose but can yield equivocal conclusions. This study evaluated whether next-generation sequencing (NGS) using the 50-gene AmpliSeq Cancer Hotspot Panel version 2 can help facilitate this distinction. NGS was performed on known primary-metastatic pairs (8 patients) and multiple lung adenocarcinomas (11 patients). Primary-metastatic pairs had high mutational concordance. Seven pairs shared mutations, and 1 was concordant for having no mutations. Driver mutations in KRAS (n = 4), EGFR (n = 2), and BRAF (n = 1) were always concordant. Multiple lung tumors from 3 patients were completely concordant and predicted by NGS to be intrapulmonary metastases, whereas 8 had completely discordant mutations and were predicted to be independent primary tumors. The NGS prediction correlated with the AJCC (eighth edition) prediction in all patients for whom the latter was unequivocal (8 of 11). Furthermore, it separated patients by overall survival. Patients with predicted multiple independent primary tumors by NGS had better survival than those with distant metastases (P=0.016, log-rank test), whereas those with predicted intrapulmonary metastases had no difference (P=0.527). With further validation, the 50-gene panel has the potential to serve as an adjunct to the AJCC criteria.

Validation of the Eighth AJCC New Substages forBladder Cancer Among Different StagingContexts.

To validate the prognostic value of the new American Joint Committee on Cancer (AJCC) staging system (eighth edition) among different staging contexts (clinical vs. pathologic). Surveillance, Epidemiology, and End Results (SEER) database (2010-2014) was accessed through SEER*Stat program and both AJCC seventh and eighth edition stages were assigned for each patient. Overall and cancer-specific survival analyses according to both editions were conducted through Kaplan-Meier analysis. Concordance index (c-index) was assessed for each edition. A total of 7074 patients with pathologically staged and 26,698 with clinically staged urinary bladder carcinoma were identified in the period from 2010 to 2014. Among patients with pathologically staged disease without neoadjuvant treatment, P values for all pairwise comparisons among different stages (according to AJCC seventh and eighth systems) were significant for both overall and cancer-specific survivals (< .01). Moreover, within the same cohort, c-index (using death from urinary bladder cancer as the dependent variable) for AJCC seventh system was 0.714 (SE 0.008; 95% CI, 0.699-0.729); whereas the c-index for the AJCC eighth system was 0.718 (SE 0.008; 95% CI, 0.702-0.733). Likewise, among patients with clinically staged disease, P values for all pairwise comparisons among different AJCC eighth stages were significant for overall survival (< .05) except for stage IIIA versus stage IIIB; whereas P values for all pairwise comparisons among different AJCC eighth stages were significant for cancer-specific survival (P< .05). This analysis supports the prognostic relevance of the added substages described within AJCC eighth edition stages III and IV for clinically staged and pathologically staged disease without neoadjuvant treatment.

Prognostic value of the eighth edition AJCC TNM classification for differentiated thyroid carcinoma

BackgroundThe prognostic value of the proposed eighth edition of the American Joint Committee on Cancer (AJCC) tumor, node, and metastasis (TNM) classification is currently unclear. The aim of the study was to evaluate the prognostic value of the eighth edition of the AJCC TNM classification. MethodsWe retrospectively assessed 3176 patients with differentiated thyroid carcinoma (DTC) who underwent thyroidectomy at a tertiary Korean hospital from 1996 to 2005. Cancer-specific survival (CSS) was analyzed using the Kaplan–Meier method and compared using the log-rank test. Performance of the eighth edition TNM with respect to prediction of CSS was assessed against the current seventh edition. ResultsUpon reclassification according to the eighth edition, 37.6% of patients were down-staged. The proportions of stage I and II tumors increased from 61.9% to 81.1% and from 1.7% to 16.0%, respectively, whereas those of stage III and IVB (formerly IVC in the seventh edition) decreased from 27.6% to 2.3% and 0.8% to 0.5%, respectively. The proportions of variance explained (PVEs) for the ability of the eighth and the seventh edition to predict CSS were 3.9% and 2.9%, respectively. The C-index values were 0.765 (95% confidence interval 0.764–0.766) for the eighth edition and 0.736 (0.735–0.737) for the seventh edition. ConclusionOur results demonstrate that the eighth edition TNM more accurately predicts CSS for patients with DTC than does the seventh edition.

The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging.

The American Joint Committee on Cancer (AJCC) staging manual has become the benchmark for classifying patients with cancer, defining prognosis, and determining the best treatment approaches. Many view the primary role of the tumor, lymph node, metastasis (TNM) system as that of a standardized classification system for evaluating cancer at a population level in terms of the extent of disease, both at initial presentation and after surgical treatment, and the overall impact of improvements in cancer treatment. The rapid evolution of knowledge in cancer biology and the discovery and validation of biologic factors that predict cancer outcome and response to treatment with better accuracy have led some cancer experts to question the utility of a TNM-based approach in clinical care at an individualized patient level. In the Eighth Edition of the AJCC Cancer Staging Manual, the goal of including relevant, nonanatomic (including molecular) factors has been foremost, although changes are made only when there is strong evidence for inclusion. The editorial board viewed this iteration as a proactive effort to continue to build the important bridge from a "population-based" to a more "personalized" approach to patient classification, one that forms the conceptual framework and foundation of cancer staging in the era of precision molecular oncology. The AJCC promulgates best staging practices through each new edition in an effort to provide cancer care providers with a powerful, knowledge-based resource for the battle against cancer. In this commentary, the authors highlight the overall organizational and structural changes as well as "what's new" in the Eighth Edition. It is hoped that this information will provide the reader with a better understanding of the rationale behind the aggregate proposed changes and the exciting developments in the upcoming edition. CA Cancer J Clin 2017;67:93-99. © 2017 American Cancer Society.