8th Edition AJCC Staging Research Articles

SAT-461 NIFTP: A Painstaking Diagnosis Through the Pathologist’s Eyes

Non-invasive encapsulated follicular variant of papillary thyroid cancer (EFVPTC) was recently reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFT-P).1 In 2018, revised and stricter criteria were proposed for a lesion to qualify as NIFT-P including no well-formed papilla or BRAF-V600E mutation.2 We are presenting an interesting case to highlight the importance of scrutinizing pathology slides to diagnose NIFTP with these more strict criteria.35-year-old female from Puerto-Rico was diagnosed with Graves’ disease. After 2 years of methimazole treatment, total thyroidectomy was planned for definitive treatment of Graves’ disease. During the work up, she was noted to have a cystic nodule in isthmus, a 1.1 cm hypoechoic nodule in left mid-lobe and a 1.1 cm isoechoic rounded mass in left level III neck, which was initially thought to be a lateral aberrant thyroid remnant. Her thyroid uptake scan was consistent with a multinodular goiter with no uptake in the extrathyroidal mass. The mass was biopsied and showed Atypia of Undetermined Significance (AUS) Bethesda III with washout positive for thyroglobulin (Tg). Total thyroidectomy with bilateral central and left lateral neck dissection was performed. The pathology showed an intrathyroidal 1.2 cm EFVPTC with predominant follicular features and <1% papillae, without tumor capsular invasion. The initial diagnosis was NIFT-P with a background of chronic thyroiditis. However, on pathology, the level III neck mass was a 2 cm metastatic node with classical PTC. ThyroSeq mutational analysis of tissue blocks for both the thyroid nodule and lymph node were positive for NCOA4-RET (RET-PTC3) gene fusion, a BRAF-V600E-like mutation found in classical PTC. On review of her pathology, the thyroid lesion was noted to have more than one papilla, though <1% papillae and was >30% solid, hence not qualifying as NIFT-P and her histological diagnosis was changed to EFVPTC. She was staged as AJCC 8th edition stage 1 with intermediate ATA risk for which she received adjuvant therapy of 101 mCi 131I.Although classification into NIFT-P has been shown to reduce overtreatment of low risk encapsulated PTC, pathology slides should be closely scrutinized to ensure fulfillment of all criteria in order for a lesion to qualify as NIFT-P. This will minimize failure to recognize PTCs, that would warrant closer follow up and surveillance for recurrence.1. Rossi, Esther D, et al. Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: Update and Diagnostic Considerations—a Review. Endocrine Pathology 30.2 (2019)2. Nikiforov, Yuri E et al. Change in Diagnostic Criteria for Noninvasive Follicular Thyroid Neoplasm With Papillary-like Nuclear Features. JAMA oncology vol. 4,8 (2018)

SUN-426 The Impact from AJCC 8Th Edition Staging System on Thyroid Cancer Outcomes by Race And Ethnicity

Background. Previous studies have demonstrated racial and ethnic outcome disparities among differentiated thyroid cancer (DTC) patients. However, the impact of the 8th edition of the American Joint Committee on Cancer staging system (AJCC8) on these disparities is unknown. Methods. DTC patients with sufficient tumor and survival data were identified in the National Cancer Database from 2004-2013. The 7th edition of the staging system (AJCC7) and AJCC8 criteria were compared. Multivariable logistic regression was used to evaluate the association between AJCC7 to AJCC8 staging change and race and ethnicity. Cox-proportional hazards regression was then used to evaluate the association between AJCC7 to AJCC8 staging change and overall survival. Results. Of 33,323 DTC patients, 76.7% were White/Non-Hispanics, 7.6% Blacks, 6.7% Hispanics, 5.4% Asian/Pacific-Islanders, and 3.6% Native-American/Other. Most were female (77%) with papillary DTC (90%). After adjusting for demographic, tumor, and treatment characteristics, Hispanics and Asian/Pacific-Islanders were 27% and 12% less likely to be AJCC7 to AJCC8 downstaged than White/Non-Hispanics (OR=0.73, 95%CI: 0.66-0.81; and OR=0.88, 95%CI: 0.79-0.99, respectively); Blacks had no significant downstaging difference compared to White/Non-Hispanics (OR=0.99, 95% CI: 0.90-1.09, p=0.79). Although AJCC8 was a better survival prognosticator than AJCC7, Cox-proportional hazards regression showed that all AJCC7 to AJCC8 downstaged patients had an increased risk of death compared to patients with unchanged staging, regardless of race and ethnicity: White/Non-Hispanics (HR=2.64, 95%CI: 2.34-2.98), Blacks (HR=1.77, 95%CI: 1.23-2.54), Hispanic (HR=3.27, 95%CI: 2.05-5.22), Asian/Pacific-Islanders (HR=2.31, 95%CI: 1.35-3.98), and Native-American/Other (HR=5.26, 95%CI: 2.10-13.19). However, based on two way interaction, the magnitude of negative change in survival from downstaging was only different between White/Non-Hispanics and Blacks (HR=2.64 vs. HR=1.77, respectively; p=0.04). Conclusions. Racial and ethnic outcome disparities persist with AJCC8. The proportion of downstaged DTC patients with AJCC8 varies by race and ethnicity, with the least impact found in Hispanics and Asian/Pacific-Islanders. Downstaged patients across all racial and ethnic groups had a decreased survival than those with unchanged stage, with the least impact in Blacks. These disparities should be taken into account when counseling patients about their prognosis with the new AJCC8.

Overuse of Diagnostic Brain Imaging Among Patients With Stage IA Non-Small Cell Lung Cancer.

Among patients diagnosed with stage IA non-small cell lung cancer (NSCLC), the incidence of occult brain metastasis is low, and several professional societies recommend against brain imaging for staging purposes. The goal of this study was to characterize the use of brain imaging among Medicare patients diagnosed with stage IA NSCLC. Using data from linked SEER-Medicare claims, we identified patients diagnosed with AJCC 8th edition stage IA NSCLC in 2004 through 2013. Patients were classified as having received brain imaging if they underwent head CT or brain MRI from 1 month before to 3 months after diagnosis. We identified factors associated with receipt of brain imaging using multivariable logistic regression. Among 13,809 patients with stage IA NSCLC, 3,417 (25%) underwent brain imaging at time of diagnosis. The rate of brain imaging increased over time, from 23.5% in 2004 to 28.7% in 2013 (P=.0006). There was significant variation in the use of brain imaging across hospital service areas, with rates ranging from 0% to 64.0%. Factors associated with a greater likelihood of brain imaging included older age (odds ratios [ORs] of 1.16 for 70-74 years, 1.13 for 75-79 years, 1.31 for 80-84 years, and 1.46 for ≥85 years compared with 65-69 years; all P<.05), female sex (OR, 1.09; P<.05), black race (OR 1.23; P<.05), larger tumor size (ORs of 1.23 for 11-20 mm and 1.28 for 21-30 mm tumors vs 1-10 mm tumors; all P<.05), and higher modified Charlson-Deyo comorbidity score (OR, 1.28 for score >1 vs score of 0; P<.05). Roughly 1 in 4 patients with stage IA NSCLC received brain imaging at the time of diagnosis despite national recommendations against the practice. Although several patient factors are associated with receipt of brain imaging, there is significant geographic variation across the United States. Closer adherence to clinical guidelines is likely to result in more cost-effective care.

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

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

Development and validation of novel nomograms for predicting the survival of patients after surgical resection of pancreatic ductal adenocarcinoma.

Background/AimsPancreatic ductal adenocarcinoma (PDAC) is associated with high mortality, even after surgical resection. The existing predictive models for survival have limitations. This study aimed to develop better nomograms for predicting overall survival (OS) and cancer‐specific survival (CSS) in PDAC patients after surgery.MethodsA total of 6323 PDAC patients were retrospectively recruited from the Surveillance, Epidemiology, and End Results (SEER) database and randomly allocated into training, validation, and test cohorts. Multivariate Cox regression analysis was conducted to identify significant independent factors for OS and CSS, which were used for construction of nomograms. The performance was evaluated, validated, and compared with that of the 8th edition AJCC staging system.ResultsTen independent factors were significantly correlated with OS and CSS. The 1‐, 3‐, and 5‐year OS rates were 40%, 20%, and 15%, and 1‐, 3‐, and 5‐year CSS rates were 45%, 24%, and 19%, respectively. The nomograms were calibrated well, with c‐indexes of 0.640 for OS and 0.643 for CSS, respectively. Notably, relative to the 8th edition AJCC staging system, the nomograms were able to stratify each AJCC stage into three prognostic subgroups for more robust risk stratification. Furthermore, the nomograms achieved significant clinical validity, exhibiting wide threshold probabilities and high net benefit. Performance assessment also showed high predictive accuracy and reliability.ConclusionsThe predictive ability and reliability of the established nomograms have been validated, and therefore, these nomograms hold potential as novel approaches to predicting survival and assessing survival risks for PDAC patients after surgery.

Liquid Biopsy as Effective Predictor of Stage III Melanoma Relapse

Liquid Biopsy as Effective Predictor of Stage III Melanoma Relapse

Abstract P5-06-23: Comparison of the AJCC eighth edition prognostic stage and anatomic stage in different histological breast cancer types and proposal of a novel score system

Abstract Background: The objective of the current study was to validate the prognostic staging system (PS) proposed in AJCC 8th edition staging manual among patients with invasive ductal carcinoma (IDC) and patients with invasive lobular carcinoma (ILC) respectively, and to compare the predictive performances of PS in both cohorts. Method: Patients diagnosed with IDC and ILC from 2010 to 2015 in the Surveillance, Epidemiology and End Results (SEER) database were retrospectively identified. Patients were restaged according to anatomic staging system (AS) and PS. Disease-specific survival (DSS) and overall survival (OS) were estimated by Kaplan-Meier method. The predictive performances of different staging systems were quantified and compared based on Harrell’s concordance index (C-index) and Akaike information criterion (AIC) calculated from Cox models. New staging score systems were established by assigning points to DSS-associated prognostic factors to improve risk stratification. Results: A total of 184,541 female patients were included in the final analyses, with 166,084 (90%) cases in the IDC cohort while 18,475 (10%) cases in the ILC cohort. Stage distribution and survival outcomes of different stages were showed in Table1. In IDC cohort, the PS (C-index, 0.8281; AIC, 110274.5) showed superiority in risk stratification compared with the AS (C-index, 0.8125; AIC, 112537.0; P&amp;lt;0.001 for C-index) with respect to DSS. In ILC cohort, the PS (C-index, 0.8281; AIC, 7124.423) was not superior to the AS (C-index, 0.8324; AIC, 7144.818; P=0.748 for C-index) in prognosis prediction with respect to DSS. Similar results were observed with respect to OS. Among three score systems specially designed for ILC patients, the score system defined by AS plus grade plus estrogen receptor and progesterone receptor (AS+GEP) allowed for better staging (C-index, 0.8085; AIC 7178.448). Detailed point assignments were listed in Table2. Conclusion: Compared with AS, the PS provided more accurate stratification for patients with IDC, but not for patients with ILC. The AS+GEP score system may fit ILC tumors better. Further investigation was needed to refine tumor staging. Table1. Distribution and survival outcomes by anatomic stages and prognostic stages in IDC cohort(N=166,084) and ILC cohort(N=18,475).StageIDC cohortILC cohortN (%)4-year DSS4-year OSN (%)4-year DSS5-year OSASIA85807(51.7)98.7195.687779(42.1)99.2395.99IB4500(2.7)97.7495.63326(1.8)98.6394.57IIA38186(23.0)95.2591.314596(24.9)97.4392.75IIB19762(11.9)91.2387.282628(14.2)96.3492.13IIIA10879(6.6)84.5381.462010(10.9)92.0587.14IIIB2831(1.7)75.3368.83202(1.1)74.6568.15IIIC4119(2.5)71.8267.22916(5.0)77.5573.94PSIA102448(61.7)98.8695.7012156(65.9)98.8095.27IB25722(15.5)95.7292.203553(19.3)95.4991.22IIA17329(10.4)91.0087.13757(4.1)95.1189.06IIB6599(4.0)86.7183.40541(2.9)91.6886.15IIIA7092(4.3)82.3078.281049(5.7)83.0177.15IIIB3431(2.1)76.0071.12313(1.7)72.3369.12IIIC3463(2.1)57.4352.3887(0.5)52.5348.09 Table 2. Univariate and multivariate analyses for factors associated with DSS and point assignment in ILC cohort.FactorUnivariate analysisMultivariate analysisModel AS+GModel AS+GEPHRPHRPHRPPointStageIA1/11/0IB1.84&amp;lt;0.0011.750.3541.870.2690IIA3.34&amp;lt;0.0013.15&amp;lt;0.0013.15&amp;lt;0.0011IIB5.31&amp;lt;0.0014.91&amp;lt;0.0015.04&amp;lt;0.0012IIIA10.74&amp;lt;0.0019.76&amp;lt;0.0019.82&amp;lt;0.0013IIIB30.16&amp;lt;0.00126.49&amp;lt;0.00123.86&amp;lt;0.0014IIIC31.41&amp;lt;0.00127.90&amp;lt;0.00126.06&amp;lt;0.0014Grade11/11/021.75&amp;lt;0.0011.43&amp;lt;0.0012.380.014134.30&amp;lt;0.0012.47&amp;lt;0.0012.06&amp;lt;0.0011ER statusPositive1/1/0Negative6.85&amp;lt;0.0012.51&amp;lt;0.0011PR statusPositive1/1/0Negative2.47&amp;lt;0.0011.75&amp;lt;0.0011HER2 statusNegative1/Positive1.270.253Abbreviations for tables: AS, anatomic staging system; PS, prognostic staging system; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; DSS, disease -specific survival; OS, overall survival; HR, hazard ratio; ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor 2; AS+G,anatomic stage plus grade; AS+GEP, anatomic stage plus grade plus estrogen receptor plus progesterone receptor. Citation Format: Shuning Ding, Jiayi Wu, Caijin Lin, Lisa Andriani, Weilin Chen, Deyue Liu, Li Zhu. Comparison of the AJCC eighth edition prognostic stage and anatomic stage in different histological breast cancer types and proposal of a novel score system [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-06-23.

The Double-Edge Role of the Addition of Adjuvant Chemotherapy to Concurrent Chemoradiotherapy in the Treatment of Nasopharyngeal Carcinoma.

PurposeTo construct a prognostic index (PI) for overall survival (OS) to stratify nasopharyngeal carcinoma (NPC) into high-risk and low-risk groups. We also applied the model to investigate the role of the addition of adjuvant chemotherapy (AC) to concurrent chemoradiotherapy (CCRT) regimens for the treatment of NPC.MethodsA prognostic model was established based on a retrospective study of 362 patients from January 2008 to June 2011. The discriminative and calibration abilities of the model were evaluated by Harrell’s concordance index (C-index), and calibration curves. Bootstrapping was used to perform for internal validation. External validation was conducted using 324 patients diagnosed with NPC from July 2011 to December 2012 at the same institution. Survival analyses were performed between CCRT-AC and CCRT alone groups for the high-risk and low-risk groups.ResultsThe primary PI comprised covariates that were associated with OS in the training cohort, including T stage, N stage, age, and plasma alkaline phosphatase (ALP). Internal and external validation showed that the discrimination of the PI for OS was significantly better than that of the 8th edition AJCC staging system. Discretization by using a fixed PI score cut-off of 407.96 determined from the training data set yielded high- and low-risk subgroups with distinct OS outcomes in the validation cohort. Adjuvant chemotherapy improved OS in high-risk patients (HR 0.620, 95% CI 0.408 to 0.941; P = 0.023) but increased the risk of distant metastasis (HR, 4.222, 95% CI, 0.959 to 18.585; P = 0.038) in low-risk patients.ConclusionThe proposed prognostic model achieved good prediction and calibration of OS for patients with NPC. The addition of adjuvant chemotherapy might be a double-edged sword, bringing survival benefit to high-risk patients but greater risk of distant metastasis to low-risk patients.

Implications for Breast Cancer Restaging Based on the 8th Edition AJCC Staging Manual.

We assessed the changes that have resulted from the latest breast cancer staging guidelines and the potential impact on prognosis. Contemporary data suggest that combining anatomic staging and tumor biology yields a predictive synergy for determining breast cancer prognosis. This forms the basis for the American Joint Committee on Cancer's (AJCC) Staging Manual, 8th edition. We assessed the changes that have resulted from the new staging guidelines and the potential impact on prognosis. Women with stages I to III breast cancer from 2010 to 2014 in the National Cancer Data Base were pathologically staged according to the 7th and 8th editions of the AJCC Staging Manual. Patient characteristics and restaging outcomes were summarized. Unadjusted overall survival (OS) was estimated, and differences were assessed. Cox proportional-hazards models were utilized to estimate the adjusted association of stage with OS. After restaging the 493,854 women identified, 6.8% were upstaged and 29.7% were downstaged. The stage changes varied by tumor histology, receptor status, tumor grade, and Oncotype DX scores (all P < 0.0001). Applying the 8th edition criteria yielded an incremental reduction in survival for each increase in stage, which was not consistently seen in the 7th edition. In a subgroup analysis based on hormone receptor (HR) status, those with stages II and III, and HR- disease had a worse OS than those with HR+ disease. Applying the 8th edition staging criteria resulted in a stage change for >35% of patients diagnosed with invasive breast cancer and refined OS estimates. Overall, the transition to the 8th edition is expected to better drive clinical care, treatment recommendations, and future research.

Validation of the AJCC 8th edition staging of oral cavity squamous cell carcinoma in a UK cohort

Validation of the AJCC 8th edition staging of oral cavity squamous cell carcinoma in a UK cohort

Relevant changes in the AJCC 8th edition staging manual for oral cavity cancer and future implications.

Diagnostic confirmation and staging of cancer are primary steps in cancer patients care. Since its inception, the TNM staging system has as its main focus on an essentially anatomic classification associated with survival endpoints. Ideally, it would allow the stratification of patients in risk groups that have clearly distinct survival outcomes based on anatomic and some nonanatomic variables but similar survival outcomes within each stratum.

Difference in Outcomes for Patients with HPV Type 16 Versus HPV Non-Type 16 Oropharyngeal Squamous Cell Carcinoma

Oropharyngeal squamous cell carcinoma (OPSCC) associated with human papillomavirus (HPV) is known to have better treatment outcomes. What remains unclear is whether all HPV DNA types carry similar prognostic relevance. We aimed to evaluate disease control and survival outcomes by HPV DNA type. Patients with primary, non-metastatic OPSCC treated with curative intent were reviewed from an IRB-approved institutional database. Patients that underwent HPV DNA PCR testing with available genotype were dichotomized by the presence of HPV type 16 (HPV-16) or other (HPV-non16). Locoregional control (LRC), overall survival (OS) and disease-free survival (DFS) were determined using the Kaplan-Meier method and compared using the log-rank test. Multivariable Cox proportional hazards models were generated for OS, DFS, LRC using predictors found to be significant (p<0.05) on univariate models. A total of 205 patients were included: 150 had HPV DNA PCR testing, 120 (80%) were positive, and 114 had a known HPV type. Ninety-nine of 114 (87%) were positive for HPV16 and fifteen (13%) were positive for HPV-non16. p16 immunohistochemistry was available in 35 patients and positive in 97% of HPV16 and 100% of HPV-non16 patients. There were no significant differences in age, ECOG performance status, oropharynx subsite, AJCC 7th/8th Edition stage, smoking or alcohol use between HPV-16 and HPV-non16 patients. 3-year OS, DFS, and LRC for HPV16 and HPV-non16 was 84% v. 69% (p=0.02), 80% v. 63% (p=0.04), and 82% v. 62% (p=0.01), respectively. Multivariable models including ECOG, smoking status, AJCC 8th Edition stage, and treatment found HPV16 associated with OS (aHR 0.31, 95% CI 0.10-0.95, p=0.04) and LRC (aHR 0.33, 95% CI 0.11-0.99, p=0.05). This study provides insight into the outcomes of HPV positive oropharyngeal squamous cell carcinoma stratified by HPV16 and HPV-non16 subtypes. These data suggest that patients with HPV-non16-associated OPSCC may have worse outcomes including decreased survival and locoregional control compared to patients who carry the HPV16 subtype.

Impact of Postoperative Elective Nodal Irradiation in Pathologically Node Negative Early Stage Squamous Carcinoma of the Oral Tongue

The risk of regional recurrence in early stage (pT1-2pN0) squamous cell carcinoma of the oral tongue (OTSCC) is high even after adequate neck surgery, especially in tumors with deep invasion (DOI). Whether postoperative elective nodal irradiation (ENI) in these patients can improve regional control is still unknown. This retrospective study sets to evaluate the role of ENI in regional control in pT1-2pN0 OTSCC. Cases of OTSCC referred to Queen Elizabeth Hospital between 2004 and 2015 were extracted from the Hong Kong Cancer Registry. Inclusion criteria were pT1-2 and pN0 (AJCC 7th Edition) and primary surgery with at least an ipsilateral selective neck dissection. ENI is defined as a radiation dose of ≥ 50 Gy (EQD2) to ipsilateral level I and II or more. Independent review of the DOI of each tumor was carried out by the pathologists from the referring hospitals according to the definition set out in the AJCC 8th Edition staging manual. Regional control and survival outcomes were evaluated using log-rank test and the cox proportional hazard model. A total of 511 patients diagnosed with OTSCC were identified within the study period. 55 of them fulfilled the inclusion criteria. Median follow up was 72.9 months. 16 (29.1%) patients received ENI while 39 (70.9%) did not. ENI was not correlated with tumor grade, perineural invasion, or lymphovascular invasion, but DOI was significantly deeper for patients who received ENI (median 6.5 mm vs 10.5 mm, Mann-Whitney U, p < 0.001). When stratified by a DOI cut-off of 5 mm, the 5-year regional control is not significantly different (81.8% for < 5mm vs. 87.4% for ≥ 5 mm, p = 0.65). 5-year regional control rate with ENI is numerically higher, though statistical significance is marginal (100% vs. 80.5%, p = 0.076). Despite having a statistically significant deeper DOI, patients who received ENI had comparable regional control to those without. ENI may negate the negative prognostic impact of deep DOI. Further prospective validation study is warranted.

OTHR-08. PREDICTION OF RISK OF CENTRAL NERVOUS SYSTEM METASTASIS FOR AJCC 8TH EDITION STAGE III MELANOMA PATIENTS

Among common solid tumors, melanoma has the highest risk of CNS metastasis. Improved understanding of the incidence, risk factors, and timing of CNS metastasis is needed to inform surveillance strategies for at-risk patients. Clinical data were extracted from two institutions for AJCC 8th edition stage III melanoma patients, diagnosed from 1998–2014 who had negative baseline CNS imaging within 4 months of diagnosis. The cumulative incidence of CNS metastasis was calculated in the presence of the competing risk of death from stage III presentation, and at benchmark time points 1-, 2-, and 5-years post-diagnosis. The cohort (N=1,918) consisted of patients from major melanoma centers in the US (50.6%) and Australia (49.4%). The first site of distant metastasis was CNS only for 3.9%, CNS and extra-cranial sites (ECS) for 1.9%, and ECS only for 31.2% of patients (N=1918); 15.5% of patients who developed distant metastases (N=708) had CNS involvement at first diagnosis of stage IV disease. Cumulative incidence of CNS metastasis from stage III diagnosis was 3.7% (95% Confidence Interval (CI): 2.9–4.6) at 1-year; 9.6% (95% CI: 8.3–11.0) at 2-years; and 15.9% (95% CI: 14.2–17.7) at 5-years. In multivariable analyses, risk of CNS metastasis was significantly higher for males; younger patients; increasing AJCC stage group; scalp primary tumor site, acral melanoma subtype, and increased primary tumor mitotic rate. Conditional analyses showed that only high primary tumor mitotic rate (>9 per mm2) was significantly associated with risk of subsequent CNS metastasis among patients who survived without CNS recurrence 1-, 2-, and 5-years after the diagnosis of stage III disease. Similar rates of CNS metastasis were observed between these two large, geographically-distinct stage III melanoma patient cohorts. These results provide a framework for developing evidence-based surveillance strategies and for evaluating the impact of contemporary adjuvant therapies on the risk of melanoma CNS metastasis.

Eyelid sebaceous carcinoma: Validation of the 8th edition of the American Joint Committee on cancer T staging system and the prognostic factors for local recurrence, nodal metastasis, and survival.

To investigate the clinicopathological features and prognostic factors for eyelid sebaceous gland carcinoma (SGC) in an ethnic Chinese population and to validate the performance of the T category of the 8th edition AJCC staging systems, with the aim of providing information for refinements. Sixty-three patients with pathological diagnosis of SGC were enroled retrospectively. The clinicopathological features, treatments, and outcomes were collected. Prognostic factors associated with the outcome of local recurrence, regional lymph node metastasis, and tumour-related death were analysed. The performance analysis was performed by comparing the predictive value for survival and the monotonicity of gradients between the 7th and 8th staging systems. The distribution of T1:T2:T3:T4 tumours according to the 7th and 8th edition was 6:40:16:1 and 23:26:5:9, respectively. Positive surgical margin was a poor prognostic factor. Local recurrence was associated with more aggressive histopathological features and surrounding structure invasions. Regional lymph node metastasis was associated with larger tumours. The T category of 8th edition showed better predictability for local recurrence and regional lymph node metastasis, while the T category of 7th edition had better monotonicity of gradients. Tumours classified as T2c or worse had higher risk of regional lymph node metastasis, while tumours T3b or worse in the 8th edition had more tumour-related death. Patients with higher T category are at risk of regional lymph node metastasis and tumour-related death. Further refinement of the T category of AJCC staging system can focus on the predictability for local recurrence and the monotonicity of gradients.

Nationwide treatment patterns of oropharyngeal cancer in the human papillomavirus era.

e17521 Background: Human papillomavirus-mediated (HPV+) oropharyngeal cancer is now defined as a clinically distinct entity from HPV-unrelated (HPV-) disease in the 8th edition AJCC staging system, which more accurately informs prognosis for HPV+ patients. Treatment decisions are currently made according to the AJCC 7th ed staging. HPV+ patients are associated with favorable outcome. This study aims to analyze the national pattern of practice for HPV+ disease. Methods: Patients with oropharyngeal squamous cell carcinoma (OPSCC) diagnosed from 2010-2012 were identified from the National Cancer Database (NCDB). Patients were staged using the AJCC 7th system. Chemotherapy, radiotherapy and surgery were counted as treatment modalities. Fisher’s exact test and chi-squared test were used to assess treatment patterns over time. Overall survival (OS) was compared with Cox proportional hazards model. Results: 5,928 HPV+ OPSCC patients were identified. Single modality (surgery or radiation) was the most common treatment choice, used in 53.6% of stage I and 48.8% of stage II patients. For stage I, the use of dual modality therapy (70.8% received surgery with radiation) decreased from 36% in 2010 to 19% in 2012 (p = 0.05), though no significant difference in OS was seen between dual modality and single modality. Dual modality with chemoradiation was the main approach for stage III (58.6%) and stage IVA (67.5%) disease. Use of trimodality decreased from 2010 to 2012 in both stage III (p = 0.03) and stage IVA (p &lt; 0.01). Conclusions: Using a national cohort of HPV+ patients from the NCDB, we showed that single modality was the most common for stages I/II and dual modality was the mainstay for stages III/IVA. Usage of aggressive approaches (dual modality for stages I/II and trimodality for stages III/IVA) decreased over time. Prospective studies would be needed to determine the optimized therapeutic choice for HPV+ patients given favorable outcome.

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.

Surgery does not impact cancer-specific survival for AJCC 8th edition stage I pancreatic neuroendocrine tumors

Background: The role of surgery is unclear for stage I pancreatic neuroendocrine tumors (PNETs) based on AJCC 8th edition staging manual, which excludes high-grade and carcinomas. We examined survival outcomes in patients with stage I PNETs, and evaluated the impact of surgery on overall (OS) and cancer-specific survival (CSS). Methods: Using SEER data from 2007 to 2015 we included well- and moderately-differentiated PNET patients. Poor or undifferentiated neuroendocrine tumors and neuroendocrine carcinomas were excluded. 725 patients were identified and included in the analysis. Survival tables and log-rank, univariable and multivariable Cox regression models were used to examine OS and CSS. Results: Among the 725 patients, the majority underwent surgical treatment (n = 642, 88.6%). Median follow-up for the study population was 24 months. There were 38 overall deaths (5.24% death rate) and 12 cancer-specific deaths (1.66% death rate). All cancer-specific deaths occurred early on; all remaining deaths occurring beyond the 3-year mark were not cancer-related. Median OS and CSS were not reached, with 5-year OS and CSS rates of 91.1% and 98%, respectively for the whole population. OS was significantly lower in the non-surgical group compared to those having surgery, with 5-year OS rates of 65.0% versus 93.5% (log rank <0.01). However, CSS was no different between the two groups with 5-year CSS rates of 95.1% in the non-surgical group and 98.3% in the surgical group (log rank=0.26). On multivariable analysis, surgery was not associated with improved CSS – although it was an independent predictor of OS (see Table). Conclusion: For 8th Edition AJCC stage I PNETs, surgery is not associated with improved CSS. However, it was associated with improved OS, implying a selection bias towards surgery being performed in healthier patients. Based on these data, there is a limited role of surgery for the management of stage I PNETs and surgical treatment should be individualized, as the primary cause of death for these patients is non-cancer related.

Validation of AJCC 8th edition stage for Gall bladder cancer

Purpose: This study evaluate discriminatory value of newly proposed cancer AJCC 8th staging system compared to the AJCC 7th staging system of gallbladder cancer.

A critical analysis of the prognostic performance of the 8th edition American Joint Committee on Cancer staging for metastatic cutaneous squamous cell carcinoma of the head and neck.

The 8th edition AJCC staging of cutaneous squamous cell carcinoma of the head and neck (cSCCHN) incorporated extranodal extension (ENE) for the first time. This study compared the prognostic performance of the 7th and 8th edition staging for cSCCHN with nodal metastases. Retrospective analysis of 96 patients with metastatic cSCCHN, comparing the ability of staging systems to predict disease-specific and overall survival (OS) using the proportion of variation explained and Harrell's C-index. In AJCC8, the N classification was upstaged in 77% of patients due to the presence of ENE and 88% of patients were classified as TNM stage IV. AJCC8 was inferior to AJCC7 in predicting disease-specific survival for both N and TNM stages, and OS by TNM stage. The majority of patients with metastatic cSCCHN have ENE and are classified as TNM stage IV based on the 8th edition staging, resulting in poor prognostic performance.