8th Edition American Joint Committee Research Articles

Validation of the AJCC 8th Edition Breast Cancer Prognostic Staging System in Legacy Alliance Trials (AFT-01).

The 8th edition American Joint Committee on Cancer staging system combined anatomic stage (AS) with receptor status and grade to create prognostic stage (PS). PS has been validated in single-institution and cancer registry studies; however, missing human epidermal growth factor receptor 2 (HER2) status and variable treatment and follow-up create limitations. Our objective was to compare the relative prognostic ability of PS versus AS to predict survival using breast cancer clinical trial data. Women with non-metastatic breast cancer enrolled in six Alliance for Clinical Trials in Oncology trials were included (enrollment years 1997-2010). AS and PS were constructed using pathological tumor size, nodal status, estrogen receptor (ER), progesterone receptor (PR), HER2 status, and grade. Unadjusted Cox proportional hazard models were estimated to predict overall survival within 5 years, with AS and PS as predictor variables. The relative predictive power of staging models was assessed by comparing Harrell concordance indices (C-indices). Kaplan-Meier-based mortality estimates were compared by stage. Overall, 6924 women were included (median age 53years); 45.2% were diagnosed with ER+/PR+/HER2- tumors, 26.2% with HER2+ tumors, and 17.1% with ER-/PR-/HER2- tumors. Median follow-up time was 5 years (interquartile range 2.95-5.00). PS significantly improved predictive performance (C-index 0.721) for overall survival compared with AS (0.700) (p=0.020). Kaplan-Meier hazard estimates suggested PS did not distinguish mortality risk between patients with IIB and IIIA or IB and IIA disease. PS has significantly improved predictive performance for OS compared with AS. As systemic therapies evolve, it will be important to re-evaluate the prognostic staging system, particularly for patients with intermediate-stage cancers. gov Identifier: NCT02171078.

Retinoblastoma in Asia: Clinical Presentation and Treatment Outcomes in 2112 Patients from 33 Countries

PurposeTo describe the clinical presentation and treatment outcomes of children diagnosed with retinoblastoma (RB) in the year 2017, throughout Asia. DesignMulti-national prospective study including treatment-naïve patients diagnosed with retinoblastoma in Asia during 2017 and followed up thereafter. ParticipantsA total of 2112 patients (2797 eyes) from 96 RB treatment centers in 33 Asian countries. InterventionChemotherapy, radiotherapy, enucleation, orbital exenteration Main Outcome MeasuresEnucleation and death ResultsWithin the cohort, 1021 (48%) patients were from South Asia (SA), 503 (24%) from East Asia (EA), 310 (15%) from South-East Asia (SEA), 218 (10%) from West Asia (WA) and 60 (3%) from Central Asia (CA). Mean age at presentation was 27 months (median, 23 months; range, <1 to 261 months). There were 1195 (57%) males and 917 (43%) females. The most common presenting complaints were leukocoria (72%) and strabismus (13%). Based on 8th edition American Joint Committee for Cancer, tumors were staged as cT1 (n=441; 16%), cT2 (n=951; 34%), cT3 (n=1136; 41%), cT4 (n=267; 10%), N1 (n=48; 2%), and M1 (n=129; 6%) at presentation. RB was treated with intravenous chemotherapy in 1450 (52%) eyes and 857 (31%) underwent primary enucleation. Three-year Kaplan-Meier estimates for enucleation and death were 33% and 13% for CA, 18% and 4% for EA, 27% and 15% for SA, 32% and 22% for SEA, 20% and 11% for WA (p<0.0001 and p<0.0001), respectively. ConclusionAt the conclusion of this study, there was a significant heterogeneity in treatment outcomes of RB between the regions of Asian continent. East Asia displayed better outcomes with higher rates of globe and life salvage, while South-East Asia had poorer outcomes compared to the rest of Asia.

Positive margin and advanced depth of invasion as the indicators for assessing the necessity of adjuvant chemoradiotherapy in early-stage oral cavity squamous cell carcinoma.

e18052 Background: Adjuvant therapy was indicated for patients with a high risk of disease progression after curative therapy, and RTOC 9501/EORTC 22931 were the landmark studies for assessing the necessity of adjuvant therapy in oral cavity squamous cell carcinoma (OCSCC). However, the role of adjuvant therapy in early-staging OCSCC, which was redefined by the 8th edition American Joint Committee on Cancer (AJCC) staging system, was unknown. Methods: A total of 485 early-staging OCSCC patients (pT1-2N0) diagnosed between Jan 2010 and Dec 2019 were retrospectively enrolled. All of them were newly diagnosed and reevaluated to meet the criteria of the 8th edition AJCC staging system. Adjuvant therapy was discussed and concluded in the combined conference of the head and neck multidisciplinary team at Chung Shan Medical University Hospital. And the enrolled patients were divided into the groups with or without adjuvant therapy. The effectiveness of adjuvant therapy and prognostic factor for locoregional recurrence-free survival (LRFS) were analyzed. Results: Nearly one-sixth (16.1%, 78/485) of the enrolled patients received adjuvant therapy. The patients with adjuvant therapy were worse in pathologic T staging ( P &lt; 0.001), histologic grade ( P &lt; 0.001), and pathologic features (depth of invasion [DOI] &gt; 4mm, P &lt; 0.001; perineural invasion, P &lt; 0.001) than those without. Positive margin and advanced DOI ( &gt; 4mm) were the independent factors for LRFS. Adjuvant therapy did not improve LRFS that the 3-year LRFS of the patients with or without adjuvant therapy were 79.7% and 81.5%, respectively ( P = 0.718)(hazard ratio [HR], 95% confidence interval [CI]: 1.10 [0.67-1.80]). However, adjuvant chemoradiotherapy (CRT) indeed prolonged LRFS in some subgroups, such as those with positive margin or advanced DOI (the subgroup with positive margin, 3-year LRFS of those with or without adjuvant therapy, 100% and 58.8%, HR[95% CI]: 0.04[0.00-267.330]; the subgroup with advanced DOI, 3-year LRFS, 83.3% and 73.1%, HR[95% CI]: 0.48[0.16-2.01]). In addition to positive margin, advanced DOI was the most critical correlation coefficient factor among the pathologic features, including pathologic T staging, perineural invasion, lymphovascular invasion, poorly differentiated, and close margin. For the patients eligible for evaluation, forty percent (40.1%, 180/439) of the patients were diagnosed with positive margins or advanced DOI and these patients might be considered to receive adjuvant CRT in the future. Conclusions: Positive margin and DOI were the most important indicators to evaluate the necessity of adjuvant CRT in early-staging OCSCC. Future warranted studies were needed.

Early Stage Melanoma of the Vermillion with Mucosal Melanoma in Situ: A Clinical Conundrum

BackgroundMelanoma is a predominantly cutaneous malignancy associated with sun exposure. Mucosal melanoma is rare and carries a distinct pathogenesis from cutaneous tumors. The vermillion of the lip is a unique site that divides cutaneous from mucosal tissues. Tumors arising on the dry aspect are classified as cutaneous and those of the wet aspect are mucosal. The distinction is importation in tumor staging as all mucosal melanomas are classified as T3-T4b under the current 8th edition American Joint Committee of Cancer (AJCC) guidelines.MethodsWe describe a case of early stage melanoma of the vermillion with associated mucosal melanoma in situ. We discuss nuances of management at this site and the distinctions between cutaneous versus mucosal melanomas with a review of the literature.ResultsOur patient was treated surgically with 2-3 cm margins. Residual melanoma in situ was present at the mucosal margin on final pathology which required a second surgery for margin revision. The case was discussed at tumor board with recommendation for no further treatment.ConclusionsThe nuances between the vermillion and mucosal lip must be understood for appropriate staging and treatment of melanomas. The paucity of literature on melanomas affecting this site render management decisions challenging. Multidisciplinary discussion is essential for guiding care.

Retrospective analysis of 8th edition American Joint Cancer Classification: Distal cholangiocarcinoma.

This is a retrospective analysis of whether the 8th edition American Joint Committee on Cancer (AJCC) was a significant improvement over the 7th AJCC distal extrahepatic cholangiocarcinoma classification. In total, 111 patients who underwent curative resection of mid-distal bile duct cancer from 2002 to 2019 were included. Cases were re-classified into 7th and 8th AJCC as well as clinicopathological univariate and multivariate, and Kaplan-Meier survival curve and log rank were calculated using R software. In patient characteristics, pancreaticoduodenectomy/pylorus preserving pancreaticoduodenectomy had better survival than segmental resection. Only lymphovascular invasion was found to be significant (hazard ratio 2.01, p = 0.039) among all clinicopathological variables. The 8th edition AJCC Kaplan Meier survival curve showed an inability to properly segregate stage I and IIA, while there was a large difference in survival probability between IIA and IIB. The 8th distal AJCC classification did resolve the anatomical issue with the T stage, as T1 and T3 showed improvement over the 7th AJCC, and the N stage division of the N1 and N2 category was found to be justified, with poorer survival in N2 than N1. Meanwhile, in TMN staging, the 8th AJCC was able differentiate between early stage (I and IIA) and late stage (IIB and III) to better explain the patient prognosis.

Comparing the predictive performance of different lymph node staging systems for postoperative overall survival in patients with ampullary carcinoma.

This study was to analyze and compare the predictive performance of the 7th and the 8th edition American Joint Committee on Cancer (AJCC) N staging system, lymph nodes ratio (LNR) and log odds of positive lymph node (LODDS) for the survival of patients with ampullary carcinomas (ACs). This retrospective cohort study included patients with primary ACs after surgery from the Surveillance, Epidemiology, and End Results (SEER) 2004-2015. Univariate and multivariate Cox proportional hazard models were used. The study population was divided into a training set and a testing set in a ratio of 7-3. The C-index and area under the curve (AUC) were used to compare the predictive performance of the four staging on overall survival (OS) in the training set and the testing set. A total of 7,480 patients with primary ACs (1,178 survived and 1,128 dead) were in this study. The average follow-up time was 41.1 months. N1 stage and N2 stage of the 8th edition AJCC N staging system, LNR staging (0-0.3), LNR (>0.3), LODDS (-2.4 to -0.8) and LODDS (>-0.8) were associated with OS in AC patients after adjusting for age, race, pT stage, tumor size, grade, radiation, and insurance. The C-index of the 7th AJCC N staging was significantly lower than the C-index of the 8th AJCC N staging in the training set [0.608 vs. 0.629, P < 0.001] and testing set [0.635 vs. 0.658, P < 0.001]. The C-index of the LODDS staging was significantly higher than the C-index of the 8th AJCC N staging in the training set [0.641 vs. 0.629, P = 0.034] and testing set [0.671 vs. 0.658, P = 0.034]. LODDS staging may be a potential predictor of OS at 6 months [AUC = 0.687], 12 months (AUC = 0.692), and 48 months (AUC = 0.709), and LNR staging (AUC = 0.655) may be a potential predictor of OS at 24 months in AC patients. The predictive ability of LNR staging and LODDS staging were also found in different subgroups. The LNR and LODDS staging systems' predictive performance for OS of AC patients were superior to the 8th edition AJCC N staging system, especially in patients ages ≥65 or with higher tumor grade (grade II and III). The LNR staging and the LODDS staging were potential predictors for 24-month OS, and 6, 12, 24 and 48-month OS, respectively.

The number of metastatic lymph nodes optimizes staging in patients aged 55 years or older with papillary thyroid cancer.

Current staging criteria for papillary thyroid cancer (PTC) do not include the number of metastatic lymph nodes (LNs), which is highly predictive of survival in multiple cancers. The LN metastasis burden is particularly relevant for older adults with thyroid cancer because of their poor prognosis. We examined a modified staging system for this population utilizing node number (Nn). Overall, 14,341 patients aged 55 years or older with stage I-IVB PTC were identified in the 2004-2015 Surveillance, Epidemiology and End Results database. Cox regression models were conducted to test the relationship between positive LN number and PTC-specific survival (PTCSS). Independent training/validation sets were used to derive and validate a new revised TNnM grouping. The 8th edition American Joint Committee on Cancer TNM staging system was compared with TNnM stage by calculating the 10-year PTCSS rates, Harrell's concordance index (C-index), and Akaike's information criterion (AIC). An increase in number of LN metastases was identified as an independent, negative prognostic factor for PTCSS in multivariate analysis. 10-year PTCSS for stage I-IVB based on the AJCC 8th edition TNM were 98.83%, 93.49%, 71.21%, 72.95%, and 58.52%, respectively, while 10-year PTCSS for the corresponding stage in the TNnM were 98.59%, 92.2%, 83.26%, 75.24%, and 56.73%, respectively. The revised TNnM stage was superior, with a higher C-index and a lower AIC in both the training and validation cohorts. The TNnM staging system for PTC patients ≥ 55 years could be associated with improved outcomes. External validation studies of this system are warranted.

A novel nomogram based on log odds of positive lymph nodes to predict survival for non-metastatic gallbladder adenocarcinoma after surgery

The prognosis of non-metastatic gallbladder adenocarcinoma (NM-GBA) patients is affected by the status of metastatic lymph nodes. The purpose of this study was to explore the prognostic value of the log odds of positive lymph nodes (LODDS) and develop a novel nomogram to predict the overall survival in NM-GBA patients. A total of 1035 patients confirmed to have NM-GBA were selected from the Surveillance, Epidemiology, and End Results (SEER) database and further divided into training and validation cohorts. The discrimination and calibration of the nomogram were evaluated using the concordance index (C-index), the area under the time-dependent receiver operating characteristic curve (time-dependent AUC), and calibration plots. The net benefits and clinical utility of the nomogram were quantified and compared with those of the 8th edition American Joint Committee on Cancer (AJCC) Tumor-Node-Metastasis (TNM) staging system using decision curve analysis (DCA), net reclassification index (NRI), and integrated discrimination improvement (IDI). The risk stratifications of the nomogram and the TNM-staging system were compared. LODDS showed the highest accuracy in predicting OS for NM-GBA. The C-index (0.730 for the training cohort and 0.746 for the validation cohort) and the time-dependent AUC (> 0.7) indicated the satisfactory discriminative ability of the nomogram. The calibration plots showed a high degree of consistency. The DCA, NRI, and IDI indicated that the nomogram performed significantly better than the TNM-staging (P < 0.05). A novel LODDS-included nomogram was developed and validated to assist clinicians in evaluating the prognosis of NM-GBA patients.

LB934 Metastatic squamous cell carcinoma is associated with a lower disease-specific survival in immunosuppressed patients: A matched case-control study

Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer with over 1 million cases and an estimated 3,932 to 8,791 deaths each year in the United States. cSCC patients have a 1-3% chance of developing metastasis which increases to 7-13% in immunosuppressed patients. The new 8th edition American Joint Committee on Cancer (AJCC8) classification system is currently used to stage cSCC, however immunosuppression is not included as a staging criterion. A review of patients with a diagnosis of cSCC seen at a tertiary referral center was conducted from 2010-2020.

Metastatic Death Based on Presenting Features and Treatment for Advanced Intraocular Retinoblastoma: A Multicenter Registry-Based Study

Purpose:To evaluate presenting features, tumor size, and treatment methods for risk of metastatic death due to advanced intraocular retinoblastoma (RB).Design:International, multicenter, registry-based retrospective case series.Participants:A total of 1841 patients with advanced RB.Methods:Advanced RB was defined by 8th edition American Joint Committee on Cancer (AJCC) categories cT2 and cT3 and new AJCC-Ophthalmic Oncology Task Force (OOTF) Size Groups (1: < 50% of globe volume, 2: > 50% but < 2/3, 3: > 2/3, and 4: diffuse infiltrating RB). Treatments were primary enucleation, systemic chemotherapy with secondary enucleation, and systemic chemotherapy with eye salvage.Main Outcome Measures:Metastatic death.Results:The 5-year Kaplan–Meier cumulative survival estimates by patient-level AJCC clinical subcategories were 98% for cT2a, 96% for cT2b, 88% for cT3a, 95% for cT3b, 92% for cT3c, 84% for cT3d, and 75% for cT3e RB. Survival estimates by treatment modality were 96% for primary enucleation, 89% for systemic chemotherapy and secondary enucleation, and 90% for systemic chemotherapy with eye salvage. Risk of metastatic mortality increased with increasing cT subcategory (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of metastatic mortality in categories cT3c (glaucoma, hazard ratio [HR], 4.9; P = 0.011), cT3d (intraocular hemorrhage, HR, 14.0; P < 0.001), and cT3e (orbital cellulitis, HR, 19.6; P < 0.001) than in category cT2a and with systemic chemotherapy with secondary enucleation (HR, 3.3; P < 0.001) and eye salvage (HR, 4.9; P < 0.001) than with primary enucleation. The 5-year Kaplan–Meier cumulative survival estimates by AJCC-OOTF Size Groups 1 to 4 were 99%, 96%, 94%, and 83%, respectively. Mortality from metastatic RB increased with increasing Size Group (P < 0.001). Cox proportional hazards regression analysis revealed that patients with Size Group 3 (HR, 10.0; P = 0.002) and 4 (HR, 41.1; P < 0.001) had a greater risk of metastatic mortality than Size Group 1.Conclusions:The AJCC-RB cT2 and cT3 subcategories and size-based AJCC-OOTF Groups 3 (> 2/3 globe volume) and 4 (diffuse infiltrating RB) provided a robust stratification of clinical risk for metastatic death in advanced intraocular RB. Primary enucleation offered the highest survival rates for patients with advanced intraocular RB.

Tumor Size, Not Small Vessel Invasion, Predicts Survival in Patients With Hepatocellular Carcinoma.

The 8th edition American Joint Committee on Cancer (AJCC) staging system for hepatocellular carcinoma (HCC) has been criticized for failing to stratify patients. We aimed to reassess and modify the tumor staging criteria for HCC. Three independent study cohorts were collected and analyzed. The initial cohort consists of 103 patients with HCC. By Kaplan-Meier survival analysis, the 8th edition failed to distinguish between T1b and T2. Only tumor size and large vessel invasion, but not small vessel invasion or other histopathologic parameters, predicted HCC survival. We modified the T staging criteria by eliminating small vessel invasion while emphasizing tumor size in the middle categories (T2 and T3), which achieved more even distribution of cases and significantly improved risk stratifications (P < .001). This modification was then validated in a cohort of 250 consecutive patients from Mount Sinai Hospital and an online Surveillance, Epidemiology, and End Results data set comprising 9,685 patients, which showed similar results. Small vessel invasion was not an independent prognostic factor in either validation cohort. Our study showed that tumor size, but not small vessel invasion, predicts survival in patients with HCC. We suggest incorporating our modified T staging criteria in future AJCC revisions.

Validation of the Prognostic Stage from the American Joint Committee on Cancer 8th Staging Manual in Luminal B-Like Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer.

PurposeThe 8th edition American Joint Committee on Cancer (AJCC) prognostic staging system (PS) has been validated numerous times; however, the prognostic value of PS for breast cancer based on molecular subtype has rarely been explored. This study aimed to investigate the prognostic value of PS in Chinese patients with luminal B-like human epidermal growth factor receptor 2 (HER2)-negative breast cancer.MethodsA total of 407 eligible cases were included in the study. All of the cases were restaged using the 8th edition AJCC Anatomic Staging System (AS) and PS. The Kaplan–Meier method was used to calculate estimated survival and the Log rank test was used to compare the survival differences between groups.ResultsThe 5-year disease-specific survival (DSS) and overall survival (OS) rates were 90.3% and 93.5%, respectively, and there were statistically significant differences in the 5-year DSS and 5-year OS rates among the different anatomic and prognostic stage groups. The application of the PS resulted in the assignment of 215 (52.8%) patients to a different group. Different prognostic stage groups restaged from anatomic Stage III had significant differences in both DSS (χ2 = 4.366, p = 0.037) and OS (χ2 = 7.549, p = 0.006); additionally, different prognostic stage groups from the anatomic Stage II group had significant differences in DSS (χ2 = 7.724, p = 0.021) but no significant differences in OS (χ2 = 5.182, p = 0.075). However, different prognostic stage groups from anatomic Stage I had no significant differences in either DSS (χ2= 0.159, p = 0.690) or OS (χ2 = 0.099, p = 0.753).ConclusionThe 8th edition AJCC PS refined the anatomic stage grouping in luminal B-like HER2-negative breast cancer and could lead to a more personalized approach to breast cancer treatment.

Maximal lymph nodal diameter on N stage of nasopharyngeal carcinoma.

To assess the maximal lymph nodal diameter on the 8th edition American Joint Committee on Cancer staging system of nasopharyngeal carcinoma (NPC).This study extracted NPC patients between 2004 and 2016 in the Surveillance, Epidemiology, and End Results database. Included patients were divided into 3 groups: ≤3 cm, >3–6 cm, and >6 cm based on the maximal lymph nodal diameter. Cumulative survival curves of 5-year overall survival (OS) and cancer-specific survival (CSS) were calculated using the Kaplan-Meier method between the 3 groups.The 5-year OS (64.0% vs 59.3%, P = .240) and CSS (71.8% vs 67.0%, P = .242) of ≤3 cm and >3–6 cm groups were not different. In contrast, the 5-year OS and CSS were different between >6 cm and ≤3 cm groups, and between >6 cm and >3–6 cm groups. The stratified hazard ratio of OS and CSS was 1.75 (95% confidence interval: 1.25–2.45; P = .001) and 1.77 (95% confidence interval: 1.20–2.60; P = .004) for the >6 cm group in the multivariate regression analysis.It is reasonable that the maximal lymph nodal diameter with >6 cm is classified as stage N3 of the 8th edition American Joint Committee on Cancer staging system for NPC.

The clinicopathologic features and the validity of the new T1 pancreatic cancer defined by the 8th edition American Joint Committee on Cancer cancer staging system

With the introduction of the eighth edition American Joint Committee on Cancer (AJCC) staging system for pancreatic cancer, several changes have been made to T1 pancreatic cancer. One of the most prominent changes was the removal of extrapancreatic extension concept, allowing many of the previously T3 tumors to be down staged to T1 pancreatic cancer. In addition, T1 was subcategorized into T1a, T1b, and T1c discriminated by 0.5 cm and 1.0 cm. The down-staging of previous T3 tumors to T1 imply that surgeons and physicians will encounter more T1 pancreatic cancer patients than before. However, the prognosis and clinicopathologic features of T1 pancreatic cancer have not been investigated in depth in the past. In addition, because of the changes in the definition of T1 pancreatic cancer, the T1 pancreatic cancer cohort defined by the eighth edition AJCC system represents a new set of patients. With increasing T1 pancreatic cancer patients, there is a need for better understanding of clinicopathologic features and prognosis of T1 pancreatic cancers. The feasibility of changes in T1 definition also needs to be investigated. The removal of the extrapancreatic extension concept was based on one study that did not present the relevant result in detail. Furthermore, prognostic insignificance of extrapancreatic concept was not reproduced in other studies. On the contrary, several studies have found extrapancreatic concept to have a prognostic significance. Subcategorization was also a problematic change. The idea of subcategorization into T1a, T1b, and T1c was proposed by Dr. Adsay to categorize small invasive carcinomas associated with premalignant cystic lesions such as intraductal papillary mucinous neoplasm. This was a proposal, and the cut-off size values were not based on scientific evidence. Therefore, it is not clear why a proposal would be incorporated into a staging system. To answer these questions, a study was initiated as a part of the 2nd Korea-Japan Collaborative Studies. Forty-two centers from Japan and Korea participated in this study and clinicopathologic data of 1,459 patients with T1 pancreatic cancer were collected for analysis. The patients were resected between 2000 and 2019. Subtypes other than pancreatic ductal adenocarcinoma and pancreatic cancers arising from premalignant cystic lesions were excluded. Patients who did not have lymph nodes assessed or had distant metastasis at surgery were excluded. Patients who received neoadjuvant treatment were also excluded from the study. This lecture aims to deliver the clinicopathologic features and the outcome of T1 pancreatic cancer. At the same time, this lecture will investigate the feasibility of the T1 definition by the eighth edition AJCC staging system for pancreatic cancer and demonstrate a need for revision in the future.

Retropharyngeal lymph node metastasis on N stage of nasopharyngeal carcinoma

PurposesTo evaluate retropharyngeal lymph node metastasis on N stage of nasopharyngeal carcinoma (NPC).MethodsNPC patients were extracted from the Surveillance, Epidemiology, and End Results database between 2004 and 2016. Pathologically confirmed patients with complete data of retropharyngeal lymph node metastasis were investigated. The included patients were divided into N1a and N1b groups. Overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan–Meier method and propensity score matching (PSM) analyses.ResultsThis retrospective cohort study examined 759 patients: 70 who were stage N1a and 689 who were stage N1b. Before PSM, N1a group was associated with similar 5-year OS (77.7% vs. 72.4%; P = 0.15) and CSS (85.6% vs. 79.9%; P = 0.09) compared to N1b group. After PSM, a similar OS (75.0% vs. 60.7%; P = 0.12) was found between the radiotherapy and chemoradiotherapy groups. However, N1a group showed a better 5-year CSS (83.8% vs. 71.1%; P = 0.04) compared to N1b group. Stage N1b was an independent risk prognostic factor for CSS (hazard ratio = 2.54, 95% confidence interval: 1.02–6.34; P = 0.04).ConclusionsOS was not different between N1a and N1b groups. Retropharyngeal lymph node metastasis defined as stage N1 of the 8th edition American Joint Committee on Cancer staging system is reasonable.

T3 versus T4a staging challenges in deeply invasive colonic adenocarcinomas and correlation with clinical outcomes

Despite the latest 8th edition American Joint Committee on Cancer Staging Manual guidelines, disagreement still exists among pathologists regarding staging deeply invasive colonic adenocarcinomas ≤1 mm to the serosal surface. In this retrospective study, 151 untreated colonic adenocarcinomas staged initially as either pT3 or pT4a and with available 5-year follow-up data were retrieved and re-categorized: Group 1 (38 cases): pT4a with tumor at the serosa; Group 2 (49 cases): tumor ≤1 mm from the serosa, with intervening reactive fibrosis (40/49) or inflammation (9/49); Group 3 (64 cases): pT3 tumor >1 mm from the serosa. Clinical outcomes were analyzed. Groups 1 and 2 tumors showed significantly lower 5-year recurrence-free survival and lower overall survival rates (log-rank p < 0.001 for both), when compared with Group 3 tumors. Even after adjusting for adjuvant therapy and nodal metastases, the proportional hazards ratios for the risk of death (p < 0.001) and risk of recurrence (p = 0.005) showed significantly higher risk in Groups 1 and 2 compared with Group 3. The synchronous nodal (p = 0.012) and metachronous distant metastases (p = 0.004) were also significantly more in Groups 1 and 2 versus Group 3. Colonic adenocarcinomas ≤1 mm from the serosal surface behaved more akin to “bona fide” pT4a tumors at the serosal surface in our study with regards to clinical outcomes. We recommend these tumors be staged as pT4a rather than pT3, as supported by outcome data in our study. We hope this will also ensure reproducibility and consistency in staging these tumors across institutions.

A relook at the 8th edition of the AJCC TNM staging system of anaplastic thyroid carcinoma: A SEER‐based study

In the 8th edition American Joint Committee on Cancer (AJCC) tumour-node-metastasis (TNM) staging system (TNM-8), changes have been made regarding anaplastic thyroid carcinoma (ATC) compared with the 7th edition (TNM-7). The major changes are that anaplastic ATC now has the same T stage definitions as differentiated thyroid cancer, and new staging of IVA and IVB is implemented. However, the clinical impact of the new edition for ATC remains unclear due to scarce and conflicting data. In this study, we compared the AJCC TNM-7 and TNM-8 in the same group of patients. In this retrospective study, we included patients who were diagnosed with ATC between 2004 and 2015; data were gathered from the Surveillance, Epidemiology and End Results (SEER) database. Overall survival (OS) was evaluated according to T stage and TNM stage according to the 7th and 8th editions. Kaplan-Meier and log-rank testing was used to analyse OS. The effect of potential predictors was estimated using the Cox regression model. We included 669 patients in the study. The median age of the cohort was 70years. During the follow-up, 600 (89.7%) patients died, 528 of whom died of thyroid cancer. The TNM-8 T staging more effectively predicted survival than the 7th edition (proportion of variation explained: 3.53% vs. 1.72%). However, the clinical stage was almost unchanged according to the TNM-8 (proportion of variation explained: 10.69% vs. 10.73%). The new T classification is an effective predictor of survival for patients with ATC. The results support the use of T definitions as per those of differentiated thyroid cancer. However, whether lymph node metastasis should be taken into account for defining ATC TNM staging should be reconsidered.

Development and validation of a new clinical staging system to predict survival for esophageal squamous cell carcinoma patients: Application of the nomogram

IntroductionSurvival of patients with the same clinical stage varies widely and effective tools to evaluate the prognosis utilizing clinical staging information is lacking. This study aimed to develop a clinical nomogram for predicting survival of patients with Esophageal Squamous Cell Carcinoma (ESCC). Materials and methodsOn the basis of data extracted from the SEER database (training cohort, n = 3375), we identified and integrated significant prognostic factors for nomogram development and internal validation. The model was then subjected to external validation with a separate dataset obtained from Jinling Hospital of Nanjing Medical University (validation cohort, n = 1187). The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index), Akaike information criterion (AIC) and calibration curves. And risk group stratification was performed basing on the nomogram scores. ResultsOn multivariable analysis of the training cohort, seven independent prognostic factors were identified and included into the nomogram. Calibration curves presented good consistency between the nomogram prediction and actual observation for 1-, 3-, and 5-year OS. The AIC value of the nomogram was lower than that of the 8th edition American Joint Committee on Cancer TNM (AJCC) staging system, whereas the C-index of the nomogram was significantly higher than that of the AJCC staging system. The risk groups stratified by CART allowed significant distinction between survival curves within respective clinical TNM categories. ConclusionsThe risk stratification system presented better discriminative ability for survival prediction than current clinical staging system and might help clinicians in decision making.

Nodal metastasis size predicts disease-free survival in cutaneous head and neck squamous cell carcinoma involving the parotid but not cervical nodes.

The 8th edition American Joint Committee on Cancer nodal (N) staging of cutaneous squamous cell carcinoma of the head and neck (cSCCHN) is largely based on lymph node metastasis size, despite conflicting data in the literature. This study aimed to investigate the prognostic significance of largest node size in cSCCHN. Retrospective analysis of 94 patients undergoing curative-intent treatment for nodal cSCCHN with surgery ± radiotherapy at Liverpool Hospital, Sydney, Australia was conducted. Survival outcomes were assessed using multivariate Cox regression. The primary end point was disease-free survival (DFS). Objective measures of model performance were used in exploratory analyses to identify optimal size thresholds for predicting survival. Nodal metastasis size significantly predicted DFS on multivariate analysis (hazard ratio 1.24; 95% confidence interval 1.06-1.46; P = 0.008). This prognostic impact occurred predominantly in parotid metastases (hazard ratio 1.27; 95% confidence interval 1.07-1.51; P = 0.006); each 1 cm increase in size increased the risk of recurrence or death by 27%, irrespective of the number of involved nodes. In parotid metastases, size thresholds of ≤3, 3-4.5 and >4.5 cm optimized prognostic discrimination. Extranodal extension (ENE) was associated with decreased DFS in nodes ≤3 cm in size (P = 0.025), but not in those >3 cm (P = 0.744). Size is an important prognostic factor in cSCCHN with parotid metastases, with optimal thresholds of ≤3, >3-4.5 and >4.5 cm. The prognostic impact of ENE was seen only in nodal metastases ≤3 cm in size. These results may have important implications for node size thresholds and inclusion of ENE in the American Joint Committee on Cancer N staging categories.

Prognostic value of the 8th edition American Joint Commission Cancer nodal staging system for patients with head and neck cutaneous squamous cell carcinoma: A multi-institutional study.

The 8th edition American Joint Committee on Cancer staging manual (AJCC8) introduced a separate staging system for head and neck cutaneous squamous cell carcinoma (HNcSCC) which parallels mucosal SCC and incorporates extranodal extension (ENE). This study aims to evaluate its prognostic utility. Univariate analysis of 1146 patients with metastatic HNcSCC from four Australian cancer centers was performed according to both AJCC 7th (AJCC7) and the 8th editions. AJCC8 increased classification of 924 (80.6%) patients to either pN2a or pN3b and 341 patients (29.8%) from stage III to IV compared to AJCC7. The disease-specific survival (DSS) was not significantly different between pN1, pN2 or pN3a categories per AJCC8. Estimates of model performance for the AJCC8 pN staging revealed modest predictive capacity (Harrell's C of 0.62 for DSS). The risk stratification according to pN classification of AJCC8 staging system performed poorly as a prognostic indicator.