8th Edition Staging System Research Articles

A better prognostic stratification for the 8th edition of the AJCC staging system of gastric cancer by incorporating pT4aN0M0 into stage IIIA

IntroductionThe aim of this study was to analyze the prognosis of gastric cancer patients categorized as pT4aN0M0, pT1N3aM0/pT2N2M0/pT3N1M0 of stage IIB and stage IIIA and to compare the optimistic prognostic stratification between the AJCC 8th edition staging system and the AJCC modified 8th (m8th) edition staging system by incorporating pT4aN0M0 into stage IIIA. Material and methodsA total of 1770 patients who underwent gastrectomy were enrolled in this study. The homogeneity, the discriminatory ability, the monotonicity of the gradient assessments, and the discriminatory ability of the AJCC 8th and m8th edition staging systems were compared by using the likelihood ratio χ2 test, a linear trend χ2 test, the Akaike information criteria (AIC) and Bayesian information criterion (BIC) calculations, respectively. ResultsFor patients staged IIB, the 5-year survival rate of the patients categorized as pT4aN0M0 were significantly worse than that of the patients categorized as pT1N3aM0/pT2N2M0/pT3N1M0 (59.9% vs. 72.4%, P = 0.036). By contrast, the prognoses of the patients between the pT4aN0M0 category and those staged IIIA were analogous (59.9% vs. 61.5%, P = 0.693). Compared with the 8th edition system, the modified 8th edition staging system had a better homogeneity (higher likelihood ratio χ [2] score, 441.17 vs. 436.24), discriminatory ability, monotonicity of gradients (higher linear trend χ2 score, 436.78 vs. 416.15) and smaller AIC (10364.98 vs. 10369.91) and BIC values (10447.13 vs. 10452.06). ConclusionsThe prognosis of pT4aN0M0 was poorer than those of pT1N3aM0, pT2N2M0, and pT3N1M0, which were staged IIB. There is a better prognostic stratification for the AJCC 8th edition staging system of gastric cancer by incorporating pT4aN0M0 into stage IIIA.

5 protein-based signature for resectable lung squamous cell carcinoma improves the prognostic performance of the TNM staging

IntroductionPrognostic biomarkers have been very elusive in the lung squamous cell carcinoma (SCC) and none is currently being used in the clinical setting. We aimed to identify and validate the...

Abstract P1-03-03: Comparing staging assignments based on the 7th and 8th editions of the American Joint Committee on Cancer staging system for breast cancer

Abstract Background: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for breast cancer has redefined breast cancer staging to better represent the heterogeneity of the disease. The previously established TNM system reflected only tumor size (T), nodal status (N), and distant metastasis (M). The updated staging system introduces new clinical and pathological prognostic staging systems by incorporating tumor grade, tumor markers, and genomic assays. Prospective comparisons of staging assignment between AJCC 7th and 8th edition staging systems have not been performed in the United States. The objective of this study was to compare subjects' assigned stage between the AJCC 7th and 8th edition staging systems. Methods: Data were collected from patients with non-metastatic breast carcinoma who presented to the University of Chicago between January 1, 2018 and May 31, 2018. Upstaging or downstaging was defined as an increase or decrease by one or more letter or number stages (i.e. from IIA to IIB or IB). Descriptive data were generated for all collected data. Analysis was performed in Stata 14.0. Results: Clinical anatomic and prognostic stages were assigned to 246 patients while pathologic anatomic and prognostic stages were assigned to 142 patients. Forty-seven patients underwent neoadjuvant therapy and were not assigned a pathologic prognostic stage, while 57 patients had not undergone surgery at our institution by the end of the study period and were not assigned a pathologic stage. Two patients had lobular carcinomia in situ and were no longer considered to have a malignancy by the 8th edition staging system; anatomic staging was otherwise unchanged from 7th edition to 8th edition staging in this cohort. Of the 246 patients assigned clinical anatomic and prognostic stages, 48 patients were upstaged (19.5%), 37 were downstaged (15.0%), and 161 were not affected (65.5%) by prognostic staging. Of the 142 patients assigned pathologic anatomic and prognostic staging, nine patients were upstaged (6.3%), 32 were downstaged (22.5%), and 101 were not affected (71.1%) by prognostic staging. Four patients were eligible to be downstaged in pathologic prognostic staging by genomic assays such as Oncotype (consisting of Stage 1B or higher patients with T1N0M0 HER2 - ER + PR - Grade 3 disease or T2N0M0 HER2 - ER + disease). Of these patients, three had genomic assays performed by the end of the study period. Results from genomic assays did not affect the staging of these three patients. Stage Changes with the AJCC 8th Edition Upstaged % (n)Downstaged % (n)No Change in Stage % (n)Clinical Stage19.5 (48)15.0 (37)65.5 (161)Pathologic Stage6.3 (9)22.5 (32)71.1 (101) Conclusions: Approximately one third of breast cancer patients were assigned new clinical or pathologic stages with the AJCC 8th edition staging system. These findings confirm that implementation of the new criteria for staging will be important to many patients in discussions of treatment and prognosis. Citation Format: Brian R, Tseng J, Bao J, Jaskowiak N. Comparing staging assignments based on the 7th and 8th editions of the American Joint Committee on Cancer staging system for breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-03-03.

M1a disease should be reconsidered in esophageal cancer staging system from the perspective of treatment response and survival after definitive concurrent chemoradiotherapy.

13 Background: M1a node involvement based on the 6th edition AJCC staging system was classified as regional node involvement in the 7th edition of esophageal squamous cell carcinoma (ESCC). However, the clinical significance of M1a node involvement based on the 6th edition staging system has not been well established. Thus, we analyzed the prognostic value of M1a node in patients of ESCC after definitive chemoradiotherapy (CCRT). Methods: A total of 188 ESCC patients had M0 disease based on the 7th edition AJCC classification, of which 31 (16.5%) of them were reclassified to the M1a patient group under the 6th edition AJCC classification. After definitive CCRT, we compared the basic characteristics of two groups, analyzed the rate of complete remission (CR), recurrence, finally assessed overall survival (OS), and disease-free survival (DFS) of each group. Results: Among 31 patients reclassified to M1a disease, 21 patients (67.7%) had subclavian nodes and 10 patients (32.3%) had celiac nodes. The median follow-up period was 18.3 months. The M1a group showed a significantly lower survival rate not only in median OS (M1a 16.4 months, M0 42.7 months, P = 0.015), but also in 5-year OS (M1a 10.8%, M0 41.2%). Three of 31 patients (9.7%) in the M1a group achieved CR, while 41 of 157 patients (26.1%) in the M0 group achieved CR ( P = 0.048). However, there was no recurrence in the M1a group after achieved CR during follow-up period. Conclusions: Among ESCC patients after completing definitive CCRT, M1a patients according to the 6th AJCC staging system showed lower CR rate and OS rate compared with M0 disease patients. M1a nodes should be differentiated from regional node involvement.

Validation of the american joint commission on cancer (AJCC) 8th staging edition in patients with pancreatic adenocarcinoma: a SEER database analysis

Background: The 8th edition AJCC staging system for pancreatic cancer incorporated several significant changes. We sought to evaluate this staging system and assess its strengths and weaknesses relative to the 7th edition system. Methods: Using the Surveillance, Epidemiology and End Results (SEER) database (2004-2013), 8,960 patients undergoing surgical resection for non-metastatic pancreatic adenocarcinoma were identified. Overall survival was estimated using the Kaplan- Meier method and compared using log-rank tests. Concordance indices were calculated to evaluate the discriminatory power of both staging systems. Cox proportional hazards model were used to determine the impact of T and N classification on overall survival. Results: The concordance index for AJCC 8th staging system (0.60,CI95% 0.59-0.61) was comparable to that for the 7th AJCC staging system (0.59,CI95% 0.58-0.60). Stratified analyses for each N classification system demonstrated diminishing impact of T classification on overall survival with increasing nodal involvement. The corresponding concordance index for N0, N1 and N2 classifications were 0.58 (CI95%:0.55-0.60), 0.53 (CI95%:0.51-0.55), and 0.53 (CI95%:0.50-0.56) respectively. Conclusion: This is the first large-scale validation of the AJCC 8th edition staging system for pancreatic cancer. The revised system provides similar discrimination as compared to the 7th edition system. However, the 8th edition system allows finer stratification of patients with resected tumors according to extent of nodal involvement.

Validation of the American Joint Commission on Cancer (AJCC) 8th Staging Edition in Patients with Pancreatic Adenocarcinoma: A SEER Database Analysis

Background: The 8th edition AJCC staging system for pancreatic cancer incorporated several significant changes. We sought to evaluate this staging system and assess its strengths and weaknesses relative to the 7th edition system. Methods: Using the Surveillance, Epidemiology and End Results (SEER) database (2004-2013), 8,960 patients undergoing surgical resection for non-metastatic pancreatic adenocarcinoma were identified. Overall survival was estimated using the Kaplan- Meier method and compared using log-rank tests. Concordance indices were calculated to evaluate the discriminatory power of both staging systems. Cox proportional hazards model were used to determine the impact of T and N classification on overall survival. Results: The concordance index for AJCC 8th staging system (0.60,CI95% 0.59-0.61) was comparable to that for the 7th AJCC staging system (0.59,CI95% 0.58-0.60). Stratified analyses for each N classification system demonstrated diminishing impact of T classification on overall survival with increasing nodal involvement. The corresponding concordance index for N0, N1 and N2 classifications were 0.58 (CI95%:0.55-0.60), 0.53 (CI95%:0.51-0.55), and 0.53 (CI95%:0.50-0.56) respectively. Conclusion: This is the first large-scale validation of the AJCC 8th edition staging system for pancreatic cancer. The revised system provides similar discrimination as compared to the 7th edition system. However, the 8th edition system allows finer stratification of patients with resected tumors according to extent of nodal involvement.

Primary surgery for human papillomavirus-associated oropharyngeal cancer: Survival outcomes with or without adjuvant treatment

ObjectivesHuman papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) is a unique form of head and neck cancer with improved prognosis. We assessed survival for stage I patients with low- or intermediate-risk pathologic features with surgery alone compared with surgery with adjuvant radiation (RT) or chemoradiation (CRT). Materials and methodsWe identified patients with stage I HPV+ OPSCC (after restaging with 8th edition staging system) treated with surgery alone, adjuvant RT or CRT in the National Cancer Data Base from 2010 to 2013. We compared survival for low-risk patients (≤1 metastatic lymph nodes with no adverse features) and intermediate-risk patients (2–4 metastatic lymph nodes, microscopic extranodal extension (ENE) or lymphovascular invasion). ResultsWe examined 1677 patients with median follow-up of 43.9 months. In the intermediate-risk group, 4-year overall survival was 94.0% with surgery alone, 91.5% with adjuvant RT and 92.0% with adjuvant CRT (p = 0.72). There were similar rates of overall survival in the low-risk group. In multivariable models accounting for clinicopathologic differences the dose of adjuvant RT was not associated with mortality. On Cox proportional hazard modeling, adjuvant RT (HR 0.94; CI 0.43–2.08) or CRT (HR 0.96; CI 0.45–2.11) did not significantly improved survival compared with surgery alone in the intermediate-risk group (reference). Similar results were seen in the low-risk group. The composite number of pathologic risk features significantly improved risk stratification. ConclusionWe provide observational evidence that adjuvant RT or CRT does not provide a survival benefit for stage I HPV+ OPSCC with low- or intermediate-risk pathologic features.

Validating the AJCC 8th Edition of the Oral Cavity Cancer Staging System: A Multi-institutional Collaborative Study

We conducted a multi-institutional study to interrogate survival outcomes in patients with oral cavity squamous cell carcinoma (OC-SCC) treated definitively grouped according to the AJCC 8th edition staging system and compared them to the 7th edition system for best fit analysis. An IRB approved collaborative database of patients with primary OC-SCC stage I-IVb (AJCC 7th edition) treated with primary surgical resection between 1/1/2005 and 1/1/2015 with or without adjuvant therapy was established from 6 academic medical centers. From a total sample size of 1282 patients, we identified 1037 patients who had sufficient staging data to be included. Survival rates were generated using Kaplan Meier analysis. A Cox proportional hazards model was generated for each staging system and Akaike information criterion (AIC) was calculated for each. The study population consisted of 647 men (62%), 868 Whites (84%) with a median age of 61 and a median f/u of 56 months (1-180). Oral tongue was the most common location (38%), followed by floor of mouth (18%), alveolus (14%) and other. All patients had primary resection, 91% had a neck dissection, 46% had postop radiation therapy alone and 37% had postop chemoradiation. The stage was changed in 388 pts (37%) in the 8th edition, all of whom were upstaged (see Table 1). Relative to stage I, AJCC 8 failed to show a significant difference in survival for stage II (HR 1.2; p=0.63) and stage III disease (HR 1.5; p=0.14), while stages IVa (HR 2.5; p<0.001) and IVb (HR 4.8; p<0.001) demonstrated significantly inferior survival. AJCC 8 5yr OS rates were similar compared to AJCC 7 for stage I (81%) and II disease (77% vs 75%), higher for stage III (72% vs 65%) and stage IVa disease (55% vs 47%), and lower for stage IVb disease (34% vs 44%), respectively. The AIC were smaller for AJCC 8 (5,804 vs. 5,841) indicating better fit. The AJCC 8th edition upstaged 37% of patients with OC-SCC leading to more uniform representation within each stage. The 8th edition outperformed the 7th edition in distinctiveness, most notably in stage IVa and IVb disease.Abstract 41; Table 1Distribution of patients according to AJCC stageAJCC 7AJCC 8TotalIIIIIIIVAIVBI804112--133II-6952--121III--11237-149IVA---379246625IVB----99Total801101764162551037 Open table in a new tab

Evaluation of the prognostic value of the new AJCC 8th edition staging system for patients with pancreatic adenocarcinoma; a need to subclassify stage III?

BackgroundThere have been several proposed changes for the 8th edition of the American Joint Commission on Cancer (AJCC) for pancreatic adenocarcinoma. The aim of this study was to evaluate the prognostic value of the new staging system for patients with pancreatic adenocarcinoma, especially in stage III patients. MethodsWe analysed the data of patients newly diagnosed with pancreatic adenocarcinoma between 2008 and 2016 at our hospital. Patients were staged according to 7th edition AJCC criteria, as well as the new 8th edition staging system. The pathologic stage was used in the surgical cases, and the clinical stage, determined by radiographic findings, was used in the unresectable cases. ResultsFive hundred two patients were identified who met the inclusion criteria. In node-negative patients, there were no significant differences in survival among T 1, 2 and 3 groups according to the 8th edition. The survival rates of patients with N1 (1–3 positive nodes) and N2 (≥4 positive nodes) disease, according to 8th edition, were significantly different (p < 0.001). Although N2 and T4 patients are both stage III according to the new staging system, N2 patients had a better survival rate than T4 patients (p = 0.038). The new staging system stratifies patients more evenly across stages without sacrificing the prognostic accuracy. ConclusionsThe AJCC 8th edition has some advantages over the previous version. However, patients with N2 and T4, who have been integrated into stage III, showed different treatment modalities and prognoses, and we proposed dividing stage III into IIIA (T1-3N2M0) and IIIB (T4NanyM0).

Does p16+ Predict a Favorable Prognosis for Oropharyngeal Cancer? Risk Factors for Treatment Failure for Patients Who Underwent Surgery-Based Therapy.

This study aimed to identify prognostic clinicopathologic factors that could predict treatment failure and to analyze clinical data from p16+ oropharyngeal squamous cell carcinoma (OPSCC) patients who underwent surgery. Data from p16+ OPSCC patients who underwent surgery at Severance Hospital of Yonsei University were retrospectively reviewed. The average smoking history was 14.6 pack-years (range 0-94 pack-years). Of the 188 patients, 73 (38.8%) underwent transoral robotic surgery (TORS) for surgical treatment of their primary lesions, and the remaining 115 patients (61.2%) underwent conventional surgery. Extracapsular nodal spread was detected in 87 patients (46.3%). At histologic examination, 67 patients (35.6%) showed positive surgical margins, and 121 patients (64.4%) had negative surgical margins. Postoperative adjuvant treatment was performed for 167 patients (88.8%). During the follow-up period, there were 18 recurrences including 2 local recurrences, 10 regional recurrences, and 6 distant metastases. During the study period, 17 deaths occurred. The univariate analysis showed that the American Joint Committee on Cancer (AJCC) 8th-edition staging system, lymphovascular invasion, more than four metastatic lymph nodes, and a smoking history of more than 10 pack-years were significantly associated with treatment failure. In the multivariate analysis, only the AJCC 8th-edition staging system was significantly associated with the patient's survival. Surgical treatment methods including TORS for p16+ OPSCC patients showed excellent oncologic results, and many previously known clinicopathologic factors did not show a significant relationship with patient prognosis. Only the newly revised AJCC 8th-edition staging system showed a significant relationship with patient survival, and this should be considered in the setting of p16+ OPSCC treatment guidelines in the future.

P1.05-23 Evaluation of the 8th Edition of the TNM Classification for Lung Cancer at a Single Institution

The 7th edition has been used more than10 y ears and has proven reliable, but various problems had been indicated.The latest (8th) edition of the lung cancer staging classification was published in 2017. The purpose of this retrospective study is to make a external validation to the 8th edition of the lung cancer staging system. Subjects included 3,229 patients who underwent pulmonary resection for primary non-small cell lung cancer.Survival characteristics were compared using the 7th and 8th editions of the staging system. According to the 7th edition, there was no significant difference between pStages IIB and IIIA(P = 0.650), however, according to the 8th edition, there were significant differences between each adjacent stage group. Moreover, to the T descriptor(tumor size), which got most emphasis in the 8th edition, there were significant differences between each adjacent pT classification, either according to the 7th edition or the 8th edition. The UICC 8th edition staging system is considered valid for non-small cell lung cancer patients and appears to be superior in defining different prognostic groups than the 7th edition.

Validation of American Joint Committee on Cancer (AJCC) 8th edition for pancreatic neuroendocrine tumor

Introduction: The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic neuroendocrine tumor (NET) included several significant changes. This study aim to evaluate this staging system compared to the 7th edition AJCC staging system. Methods: Using Korean tumor registry system - Bilary pancreas (KOTUS-BP) and Korean Pancreas Surgery Club (KPSC) database (2000–2014), 486 patients who underwent surgery for nonfunctional neuroendocrine tumor of pancreas were identified. Except for 39 (8.0%) cases with grade 3 (G3), 447 patients with G1, G2 were included in this study. Overall survival and disease free survival were calculated using the Kaplan-Meier method and compared by log-rank tests. Results: Poor discrimination in 10 years overall survival rate was noted between stage III and IV. There was 10-year disease free survival discrimination by stage: I, 93.2%; II, 83.1%; III, 38.9%; IV, 0.0% (p < .0001). Significant difference in 10 years disease free survival rate existed according to T stage (T1 93.3% vs. T2 84.8% vs. T3 53.3% vs. T4 36.0%; p < 0.001) and grade (G1 91.9% vs. G2 39.4%; p < 0.001). There was significant difference in 10 years overall survival rate between N0 versus N1 (84.4% vs. 56.3%; p = 0.001). Conclusions: This is the first large-scale validation of the AJCC 8th edition staging system for pancreatic neuroendocrine tumor. The revised 8th system provides better discrimination compared to that of the 7th-edition system.

Prognostic impact of combined immunoprofiles in oropharyngeal squamous cell carcinoma patients with respect to AJCC 8th edition.

To examine combined immunoprofiles of epidermal growth factor receptor (EGFR), CD44, and p16 in oropharyngeal squamous cell carcinoma (OPSCC) and to correlate them with radiotherapy treatment outcomes and clinicopathological parameters. Prognostic impact of the American Joint Committee on Cancer (AJCC) 8th edition staging system in comparison with 7th edition was analyzed. The study included 77 OPSCC patients treated by definitive intensity-modulated radiotherapy (IMRT). Clinical staging was assessed according to the AJCC, both 7th and 8th edition. Immunohistochemical (IHC) analysis of CD44 and EGFR was performed on primary biopsy tumor tissues. To evaluate the HPV status, IHC detection of p16 was employed. The AJCC 8th edition staging system revealed correlations between overall survival (OS), progression-free survival (PFS), locoregional control (LRC), and clinical stage. EGFR and CD44 positivity (+) and p16 negativity (-) were associated with clinical stage IV of the disease. CD44+ and EGFR+ OPSCC displayed worse OS and LRC, and these cases also showed the worst 3-year OS and LRC. Combined analysis of protein expressions identified an association between p16- and EGFR+, p16- and CD44+, EGFR+, and CD44+. Combined immunoprofiles CD44+/p16-, EGFR+/p16-, and EGFR+/CD44+ were associated with worst OS and LRC. Combined immunoprofiles of p16, EGFR, and CD44 might provide valuable prognostic and predictive information for the individual OPSCC patients, especially in terms of response to IMRT and prediction of treatment outcomes. Application of the AJCC 8th edition staging for HPV+ OPSCC proved to improve hazard discrimination and prognostication of OPSCC.

Which staging system better predicts 10-year survival for gastric cancer? A study using an international multicenter database

PurposeOur aim was to evaluate the prognostic performance of the 8th edition AJCC staging system for gastric cancer survival after 10 years or more. Patients and methodsAn international multicenter database was constructed (total n = 4537) by combining gastric cancer cases from the SEER database (n = 3066) and the database (n = 1471) of the Department of Gastric Surgery, Fujian Medical University Union Hospital. The relative discriminatory abilities were assessed using the likelihood ratio chi-square test, Akaike's Information Criterion (AIC) and Harrell's concordance index (c-statistic). ResultsThe 10-year overall survival rate for all the patients was 32.2%. A 2-step multivariate analysis showed that the 8th edition staging system was an independent factor for long-term overall survival. It also had higher likelihood ratio chi-square score, c-statistic and smaller AIC values compared with the 7th edition. However, stages IB and IIA of the TNM staging system showed a similar prognosis (both P > 0.05). Based on the survival data, we revised the 8th edition by merging stages IB and IIA into 1 category in the training set. The modified staging system demonstrated superior prognostic stratification with a higher c-statistic, likelihood ratio chi-square score and smaller AIC values compared to the 8th edition. Similar results were observed in the external validation set. ConclusionThe 8th edition AJCC TNM classification predicts the 10-year survival of gastric cancer patients more accurately than the 7th edition. However, by merging stages IB and IIA into 1 category, we propose a revised TNM stage system that provides an optimal prognosis.

Predicting prognosis in resected esophageal squamous cell carcinoma using a clinical nomogram and recursive partitioning analysis

BackgroundDevelopment demand of precise medicine in resectable esophageal squamous cell carcinoma (ESCC) require to recognize patients at high risk treated by surgery alone. Thus, our aim was to construct a clinical nomogram and recursive partitioning analysis (RPA) to predict long-term survival in ESCC treated by surgery alone. MethodsBased on the patients with ESCC who treated by three-incisional esophagectomy and two-field lymphadenectomy alone, we identified and integrated significant prognostic factors for survival to build a nomogram. The nomogram was calibrated for overall survival (OS) and the predictive accuracy and discriminative ability was measured by concordance index (c-index) and Akaike information criterion (AIC). Based on the nomogram, the RPA was performed for risk stratification. ResultsA total of 747 patients were included for analysis. Five independent prognostic factors were identified and entered into the nomogram. The calibration curves for probability of 1-, 3-, and 5-year OS showed optimal agreement between nomogram prediction and actual observation. The AIC value of the nomogram was lower than that of the 7th edition staging system, whereas the c-index of the nomogram was higher than that of the 7th edition staging system. The risk groups stratified by RPA allowed significant distinction between survival curves within respective TNM categories. ConclusionThe RPA based on a clinical nomogram appears to be suitable for risk stratification in OS for resected ESCC. This practical system may help clinicians in decision making and design of clinical studies.

Survival Outcomes of Primarily Surgically Managed HPV-Associated Oropharyngeal Carcinoma Reported by the New AJCC/UICC 8th Edition Staging System

Survival Outcomes of Primarily Surgically Managed HPV-Associated Oropharyngeal Carcinoma Reported by the New AJCC/UICC 8th Edition Staging System

Abstract P5-23-03: Gene expression profiling in male breast cancer

Abstract Background: Tumor gene expression profiling tests are widely used to quantify risk of recurrence of breast cancer and guide systemic therapy in early stage breast cancer. These assays have not been well validated in a male cohort. The purpose of this study was to determine the current rates of genomic testing in male breast cancer (MBC), the distribution of risk of recurrence scores (RRS) in early stage MBC, and the effect of RRS on systemic treatment patterns. Methods: The National Cancer Database was queried and found to include 6,227 cases of pathologic T1/T2 and N0/N1 MBC from 2008-2014 with known genomic testing status. Of the 1478 (23.74%) male patients who had gene expression profiling performed, variables of interest included age at diagnosis, stage, estrogen receptor status (ER), RRS, and treatment. We compared the treatment patterns of the 1,343 patients who had RRS available and the 4,527 patients who were not tested. A similar analysis was performed in female breast cancer (FBC) patients to serve as a point of reference. Statistical analysis included multivariate logistic regression and Pearson's chi-square test. Results: Of the 1,478 (23.74%) cases of MBC who had gene expression profiling, the most significant variables included: younger age, non-Black race, diagnosis after 2010, tumor Grade II, Estrogen Receptor (ER) positivity, and N0 or N1mi disease. Of those who had results, the distribution of RRS was 59.3% low, 27.4% intermediate, and 13.3% high. A similar distribution was found in 154,705 women who were tested during the same study period. Risk scores in men were significantly associated with tumor grade and size, but not nodal status. 83.4% of men with a low RRS were treated with hormone therapy alone, with an adjusted odds ratio (AOR) of 7.18 (CI 5.78-8.91, p&amp;lt;0.001). Also, 61.8% of men with a high RRS received combination chemotherapy and hormone therapy, with an AOR of 5.16 (CI 3.60-740, p&amp;lt;0.001). Conclusion: Although there is limited literature supporting the use of genomic assays in MBC, our study found similar rates of testing in men and women with early stage breast cancer. Treatment patterns varied significantly based on risk stratification, implying that physicians are using gene profiling assays to help guide treatment in MBC. Understanding the role for genomic profiling in MBC is particularly important as these results will be incorporated into the new AJCC 8th edition staging system. Long term follow up is needed to determine whether these tests accurately predict prognosis and recurrence in a male cohort. Citation Format: Dubrovsky E, Raymond S, Chun J, Schnabel F. Gene expression profiling in male breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-23-03.

Impact of the T and N stage in the American Joint Committee on Cancer (AJCC) 8th edition staging system for pancreatic cancer with curative resection.

261 Background: The 8th edition of the AJCC staging system for pancreatic cancer contains several changes. T and N classification incorporate tumor size and number of positive lymph node (LN). The aim of this study was to evaluate the impact on the outcomes of the new classification for the patients who underwent curative resection and received adjuvant treatment with S-1. Methods: We retrospectively reviewed 96 patients who underwent curative resection for pancreatic ductal adenocarcinoma and received adjuvant treatment with S-1 (40, 50, or 60 mg according to body-surface area, orally administered twice a day for 28 days followed by a 14-day rest, every 6 weeks [one cycle], for up to four cycles) at our institution between January 2007 and December 2015. Inclusion criteria were as follows: PS0/1, adequate-organ functions, no critical complication, start of adjuvant therapy within 10 weeks after resection, and no active concomitant malignancy. Results: 66 patients were satisfied with these criteria. Patients characteristics were as follows: median age 67 years (range, 43-83), male 40 (61%), Pancreatoduodenectomy / Distal / Total pancreatectomy 50/14/2, combined portal vein or superior mesenteric vein resection 25 (38%), no postoperative complication 25 (38%), Well/Moderately/Poorly differentiated type 23/41/2, the median tumor size 30mm (range, 13-130), the median number of dissected LN 25 (range, 10-60), the median number of positive LN 2 (range, 0-8), and the resection margin status (R0/1) 62/4. The distribution in the 8th edition (1A/1B/2A/2B/3) was 6(9%) / 10(15%) / 5(8%) / 36(54%) / 9(14%), respectively. 2-year overall survival (OS) and relapse-free survival (RFS) were 70% and 52%. In the 8th edition staging system (1A/1B/2A/2B/3), 2-year OS and RFS were 100/90/80/66/40% and 83/70/53/49/22%, respectively. 2-year OS and RFS by T classification according to AJCC 8th edition were 100/68/56% and 90/39/56% (T1/2/3), while those by N classification were 90/66/40% and 70/49/22% (N0/1/2), respectively. Conclusions: The survival was poor with progress of the stage in the new classification. Especially at N stage, it might be suggested an association with prognosis.

The AJCC 8th Edition Staging System for Soft Tissue Sarcoma of the Extremities or Trunk: A Cohort Study of the SEER Database

Background: The AJCC recently published the 8th edition of its cancer staging system. Significant changes were made to the staging algorithm for soft tissue sarcoma (STS) of the extremities or trunk, including the addition of 2 additional T (size) classifications in lieu of tumor depth and grouping lymph node metastasis (LNM) with distant metastasis as stage IV disease. Whether these changes improve staging system performance is questionable. Patients and Methods: This retrospective cohort analysis of 21,396 adult patients with STS of the extremity or trunk in the SEER database compares the AJCC 8th edition staging system with the 7th edition and a newly proposed staging algorithm using a variety of statistical techniques. The effect of tumor size on disease-specific survival was assessed by flexible, nonlinear Cox proportional hazard regression using restricted cubic splines and fractional polynomials. Results: The slope of covariate-adjusted log hazards for sarcoma-specific survival decreases for tumors >8 cm in greatest dimension, limiting prognostic information contributed by the new T4 classification in the AJCC 8th edition. Anatomic depth independently provides significant prognostic information. LNM is not equivalent to distant, non-nodal metastasis. Based on these findings, an alternative staging system is proposed and demonstrated to outperform both AJCC staging schemes. The analyses presented also disclose no evidence of improved clinical performance of the 8th edition compared with the previous edition. Conclusions: The AJCC 8th edition staging system for STS is no better than the previous 7th edition. Instead, a proposed staging system based on histologic grade, tumor size, and anatomic depth shows significantly higher predictive accuracy, with higher model concordance than either AJCC staging system. Changes to existing staging systems should improve the performance of prognostic models. Until such improvements are documented, AJCC committees should refrain from modifying established staging schemes.

Validation of the postneoadjuvant therapy pathological stage of the American Joint Committee on Cancer (AJCC) 8th Edition for predicting outcomes of esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiotherapy (CRT) followed by esophagectomy.

138 Background: The AJCC 8th edition staging system introduces a new postneoadjuvant therapy staging category (ypTNM-8th) for ESCC patients receiving neoadjuvant treatment followed by esophagectomy. Whether this new staging category has better prognostic prediction than the pathological staging category of AJCC 7th edition (ypTNM-7th) needs validation. Methods: We enrolled ESCC patients receiving neoadjuvant paclitaxel/cisplatin-based CRT (RT = 40Gy) followed by esophagectomy from three phase II trials conducted in the National Taiwan University Hospital. The prognostic prediction abilities of the ypTNM-8th and the ypTNM-7th on patients’ survivals were compared using Cox regression, concordance index (C-index), R-square, and Akaike information criteria (AIC). Results: A total 135 patients (M:F = 127: 8, median age:53.0 years) were enrolled. With a median follow-up of 31.3 months, the median PFS and OS of all patients were 24.4 months (95% CI: 15.4-33.5) and 33.9 months (95% CI: 22.6-45.1), respectively. In univariate analysis, both ypTNM-8th and ypTNM-7th had statistically significant prognostic effects for PFS and OS. In multivariate analysis on OS, the ypTNM-8th demonstrated a statistically significant predicting effect (P = 0.015) while the ypTNM-7th did not (P = 0.051). Although there is no statistically different between ypTNM-8th and ypTNM-7th by R-square analysis, the ypTNM-8th had lower AIC and C-index for both PFS and OS, meaning an better efficiency of predicting survivals, than ypTNM-7th. Conclusions: The new ypTNM-8th may have better prognostic prediction for OS of locally advanced ESCC patients receiving neoadjuvant CRT than the ypTNM-7th. (Granted by 106-HCH029)