American Joint Committee On Cancer Classification Research Articles

Proposal of New ypStage Grouping System for Esophageal Squamous Cell Carcinoma Patients who Underwent Neoadjuvant Chemoradiotherapy followed by Surgery.

To propose a new ypTNM grouping system to address these limitations and improve prognostic relevance. The current 8th edition of the American Joint Committee on Cancer (AJCC) ypStage system shows unsatisfactory prognostic relevance in patients with esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy. The study cohort included 501 ESCC patients who received nCRT followed by esophagectomy at the Samsung Medical Center in Korea between 1994 and 2018 (development cohort) and 422 patients treated at Asan Medical Center (validation cohort). Recursive partitioning with a tree-structured regression model was used to develop and validate a new ypStage grouping system. In the new ypStage grouping system, ypStage I includes ypT0N0 only; ypStage II includes ypTis-T2N0 or ypT0-T2N1; ypStage III includes ypT3N0-N1; and ypStage IV includes ypT4N0-N1 or ypTanyN2-3. This system adequately addressed the limitations of the existing AJCC classification system, including overlapping and reversal of survival rates. Moreover, the discrimination ability of the new system was higher than that of the existing system [concordance-index (C-index): 61.9%] in the development (C-index: 66.6%) and validation (C-index: 66.0%) cohorts. NRIe was 0.17 [95% confidence interval (CI): 0.09-0.26, P-<0.001) and 0.18 (95% CI: 0.10-0.27, P-<0.001)] in the development and validation cohorts, respectively. The current study proposes a clear revised version of the 8th edition of the AJCC ypStage grouping system that exhibits superior prognostic stratification in patients with ESCC treated with nCRT followed by esophagectomy.

Conjunctival melanoma: Insights into classification, outcomes, and biomarkers

Conjunctival melanoma is quite rare, estimated at approximately 0.5 incidence per 1 million persons per year. This malignancy arises from a pre-existing nevus (7%), primary acquired melanosis (74%), or de novo without pre-existing condition (19%) and develops most often in patients with Fitzpatrick skin types I (23%) and II (62%). At initial presentation, the tumor size is approximately 13 mm in cross-sectional diameter and has 3-mm thickness, involving the bulbar (97%), forniceal (30%), tarsal (28%), or caruncular (11%) regions, often with corneal (54%) and rarely with orbital (4%) involvement. According to the eighth edition of the American Joint Committee on Cancer (AJCC), the tumor is classified as T1 (63%), T2 (18%), T3 (20%), and T4 (0%). Outcomes depend on several factors including patient age, AJCC classification, orbital invasion, and type of initial surgery, whereas tumor origin and Fitzpatrick skin type do not appear to impact outcomes. Older patients (≥70 years of age) demonstrate larger tumors, greater recurrence, and greater vision loss. Analysis of 425 patients by AJCC classification (T1 versus T2 versus T3) revealed increasing T category with greater lymph node metastasis (3% versus 13% versus 25%; P < .001), tumor-related systemic metastasis (13% versus 45% versus 40%; P < .001), and tumor-related death (8% versus 22% versus 37%; P < .001). Data of patients with orbital invasion revealed significantly greater 10-year rates of exenteration (P < .001), distant metastasis (P = .0005), and death (P = .001). Studies have demonstrated biomarkers related to conjunctival melanoma include mutations in BRAF, NRAS, ATRX, and NF1. Future therapies might be directed against these mutations or with small-molecule inhibitors and/or immunotherapy. In summary, conjunctival melanoma is a rare but ominous malignancy, imparting moderate risk for lymph node and systemic metastasis as well as death, depending on tumor features and classification. The first surgery is highly important in prevention of tumor seeding, recurrence, and metastasis.

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.

Identification of high-risk patients with a seven-biomarker prognostic signature for adjuvant treatment trial recruitment in American Joint Committee on Cancer v8 stage I–IIA cutaneous melanoma

PurposeMany patients with resected American Joint Committee on Cancer (AJCC) early-stage cutaneous melanoma nonetheless die of melanoma; additional risk stratification approaches are needed. Patients and methodsUsing prospectively-collected whole-tissue sections, we assessed in consecutive stage I–IIA patients (N = 439), a previously-validated, immunohistochemistry-based, 7-biomarker signature to prognosticate disease-free survival (DFS), melanoma-specific survival (MSS; primary end-point) and overall survival (OS), independent of AJCC classification. ResultsSeven-marker signature testing designated 25.1% of patients (110/439) as high-risk (stage IA, 13.3% [43/323], IB, 53.2% [42/79], and IIA, 67.6% [25/37]). A Kaplan–Meier analysis demonstrated high-risk patients to have significantly worse DFS, MSS and OS versus low-risk counterparts (P < 0.001). In multivariable Cox regression modelling also including key clinicopathological/demographic factors, 7-marker signature data independently prognosticated the studied end-points. Models with the 7-marker signature risk category plus clinicopathological/demographic covariates substantially outperformed models with clinicopathological/demographic variables alone in predicting all studied outcomes (areas under the receiver operator characteristic curve 74.1% versus 68.4% for DFS, 81.5% versus 71.2% for MSS, 80.9% versus 73.0% for OS; absolute differences 5.7%, 10.3% and 7.9%, respectively, favouring 7-marker signature risk category-containing models). ConclusionIn patients with AJCC early-stage disease, the 7-marker signature reliably prognosticates melanoma-related outcomes, independent of AJCC classification, and provides a valuable complement to clinicopathological/demographic factors.

Acral lentiginous melanoma histotype predicts outcome in clinical stage I-II melanoma patients: an International multicenter study

BackgroundIn the American Joint Committee on Cancer (AJCC) classification, acral lentiginous melanoma (ALM) histotype ALM is not included as an independent prognostic factor; in small series its negative prognostic impact on disease-free survival (DFS) and overall survival (OS) has been linked to the greater Breslow thickness (BT).Patients and methodsThe study was carried out at four referral melanoma centers (three Italian and one Polish). Clinical consecutive patients with stage I-II melanoma, who were diagnosed, treated, and followed up between January 1998 and March 2018 in annotated specific databases were included.ResultsOverall, 6734 were evaluable, 4349 with superficial spreading melanoma (SSM), 2132 with nodular melanoma (NM), and 253 with ALM. At univariable analysis, a statistically significant worse DFS [hazard ratio (HR) 2.72, 95% confidence interval (CI) 2.24-3.30; P < 0.001] and OS (HR 2.67, 95% CI 2.15-3.32; P < 0.001) were found in patients with ALM compared with SSM. Similarly, the NM histotype was associated with a worse prognosis compared with the SSM histotype (DFS: HR 2.29, 95% CI 2.08-2.52; P < 0.001 and OS: HR 2.21, 95% CI 1.99-2.46; P < 0.001). At multivariable analysis, after adjusting for age, sex, BT, ulceration, and the sentinel lymph node status, a statistically significant worse DFS [adjusted HR (aHR; ALM versus SSM) 1.25, 95% CI 1.02-1.52; P = 0.028] was confirmed for patients with ALM. For patients with NM, instead, no impact of histology was found in terms of DFS [aHR (NM versus SSM) 1.04, 95% CI 0.93-1.15; P = 0.513] and OS [aHR (NM versus SSM) 0.96, 95% CI 0.86-1.08; P = 0.548].ConclusionsALM is associated with a worse long-term DFS. Our results could have important clinical implications for patients’ stratification in future clinical trials and the incorporation of ALM histotype in the new AJCC classification as an independent prognostic factor.

Sebaceous gland carcinoma: analysis based on the 8th edition of American Joint Cancer Committee classification.

To assess the prognostic value of T category of the 8th edition of American Joint Committee on Cancer (AJCC) classification in periocular sebaceous gland carcinoma (SGC). Retrospective interventional case series of 119 cases. Based on the T category of 8th edition of AJCC classification, 119 periocular SGCs were classified into T1 (n = 33, 28%), T2 (n = 37, 31%) T3 (n = 17, 14%) and T4 (n = 32, 27%). There were no statistically significant differences in the rate of tumour recurrence based on T category. The outcome measures that showed significant increase with increase in T category included regional lymph node metastasis (3% for T1, 3% for T2, 12% for T3, and 44% for T4; p < 0.0001), systemic metastasis (0% for T1, 0% for T2, 12% for T3, and 25% for T4; p = 0.002) and death due to metastasis (0% for T1, 0% for T2, 12% for T3, and 22% for T4; p = 0.005). The 5-year Kaplan-Meier estimate rate for regional lymph node metastasis, systemic metastasis and metastasis-related death were all higher for the T4 category tumours (42%, p = 0.005; 34%, p = 0.0002; and 43%, p = 0.0001 respectively) compared to T1 (9%, 0%, and 0%), T2 (5%, 0%, and 0%) and T3 (10%, 17 and 8%) tumours. Primary tumour (T) category of the 8th edition AJCC classification predicts the prognosis of patients with periocular SGC. The rates of lymph node metastasis, systemic metastasis, and death is much higher in T4 tumours compared to T1, T2, and T3 tumours. There was no association between T category and tumour recurrence.

Which classification system defines best prognosis of mucinous neoplasms of the appendix with peritoneal dissemination: TNM vs PSOGI?

AimsSeveral classification systems are used for pseudomyxoma peritonei. The four-tiered classification system proposed by Peritoneal Surface Oncology Group International (PSOGI) and the two-tiered proposed by the eighth edition of the...

Analysis of the relationship between the anatomical location of intrapulmonary metastatic lymph nodes and relapse risk and survival in patients with N1 non-small cell lung cancer

Objective: To evaluate the relationship between the anatomical location of intrapulmonary metastatic lymph nodes and relapse risk and survival in patients with N1 non-small cell lung cancer(NSCLC). Methods: A retrospective analysis of the clinical and pathological data of 138 patients with completely resected N1 NSCLC was conducted. There were 79 males and 59 females, aged from 26 to 81 years with an average of (59±10) years. All of them were treated in the Department of Thoracic Surgery Ⅱ of Peking University Cancer Hospital between January 2007 and December 2015. Patients were stratified based on the 8th edition of the American Joint Committee on Cancer (AJCC) N1 classification and the modified pathological N1 classification strategy, respectively. According to modified pathological N1 classification strategy, which was defined based on the anatomical location of intrapulmonary metastatic lymph nodes, N1 nodes were subcategorized into the hilar (stations 10-11, mN1b) (n=36) and peripheral (stations 12-14, mN1a) (n=102) zones. The Kaplan-Meier curves were plotted to compare the relapse risk and survival analysis, disease-free survival (DFS), and overall survival (OS) were compared between the two staging methods through univariate and multivariate analysis to evaluate the effectiveness of the two classifications in stratifying patients with distinct risks of disease relapse and survival. Results: According to the modified N1 classification, the differences in 5-year DFS and OS between the subgroups (mN1a vs mN1b) were statistically significant(59.5% vs 35.7%; 81.2% vs 56.0%; both P<0.05). However, following the 8th edition of the AJCC N1 classification, no significant differences were found in DFS and OS between the subgroups (both P>0.05). Multivariate analysis showed that the modified N1 classification was an independent prognostic factor to DFS (HR=1.814, 95%CI: 1.005-3.275) and OS (HR=3.919, 95%CI: 1.918-8.009) (all P<0.05). However, the 8th edition of the AJCC N1 classification was not an independent prognostic factor to DFS (HR=1.360, 95%CI:0.767-2.412) or OS (HR=1.620, 95%CI:0.839-3.131) (both P>0.05) as revealed by multivariate analysis. Conclusions: The relapse risk and survival could be assessed effectively using the modified pathological N1 classification, which was defined and subcategorized based on the anatomical location of intrapulmonary metastatic lymph nodes for N1 NSCLC patients. The modified pathological N1 classification is superior to the 8th edition of the AJCC classification.

Advanced ocular surface squamous cell carcinoma (OSSC): long-term follow-up

PurposeTo analyze the clinical characteristics and long-term follow-up of patients with advanced ocular surface squamous cell carcinoma (OSSC) involving periocular tissues and/or orbit. Primary outcomes were overall survival (OS), disease-free survival (DFS), and overall recurrence rate (RR). Secondary outcomes were a correlation between primary outcomes and tumor location, American Joint Committee on Cancer Classification (AJCC) staging system, histological results, surgical margins, and type of treatment. Study design: a retrospective case series.MethodsThe medical records of patients affected by OSSC involving periocular tissues and/or orbit referring, from 01/2011 to 01/2020, to our tertiary referral center were reviewed.ResultsThirty-six eyes of 36 patients were included. The mean age was 68.2 years; 18 (50%) patients were males. The mean follow-up was 40 months. The RR was 64%. The OS at 12, 24, 36, and 60 months was respectively 97.1%, 92.7%, 92.7%, and 92.7%. The DFS at 12, 24, 36, and 60 months was respectively 62.9%, 50.8%, 41.6%, and 29.7%. Multicentric disease (p = 0.0039), inferior tarsus localization (p = 0.0428), histological diagnosis of high-risk SSCs (p = 0.0264), positive surgical margins (p = 0.0434), and excisional biopsy (EB) alone (p = 0.0005) were associated with an increased risk of recurrence. A shorter OS was observed in patients who underwent EB alone (p = 0.0049).ConclusionOSCC involving periocular tissues and/or orbit is an aggressive disease with a high recurrence rate. Multicentric disease, positive surgical margins, inferior tarsus localization, and surgery without adjuvant therapies are strong predictors of recurrence and are the main factors affecting prognosis.

Detection of cancer signal for over 50 AJCC cancer types with a multi-cancer early-detection test.

3072 Background: The Circulating Cell-free Genome Atlas study (CCGA; NCT02889978) previously demonstrated that a blood-based multi-cancer early detection (MCED) test utilizing cell-free DNA (cfDNA) sequencing in combination with machine learning could detect cancer signals across multiple cancer types and predict cancer signal origin. Cancer classes were defined within the CCGA study for sensitivity reporting. Separately, cancer types defined by the American Joint Committee on Cancer (AJCC) criteria, which outline unique staging requirements and reflect a distinct combination of anatomic site, histology and other biologic features, were assigned to each cancer participant using the same source data for primary site of origin and histologic type. Here, we report CCGA ‘cancer class’ designation and AJCC ‘cancer type’ assignment within the third and final CCGA3 validation substudy to better characterize the diversity of tumors across which a cancer signal could be detected with the MCED test that is nearing clinical availability. Methods: CCGA is a prospective, multicenter, case-control, observational study with longitudinal follow-up (overall population N = 15,254). Plasma cfDNA from evaluable samples was analyzed using a targeted methylation bisulfite sequencing assay and a machine learning approach, and test performance, including sensitivity, was assessed. For sensitivity reporting, CCGA cancer classes were assigned to cancer participants using a combination of the type of primary cancer reported by the site and tumor characteristics abstracted from the site pathology reports by GRAIL pathologists. Each cancer participant also was separately assigned an AJCC cancer type based on the same source data using AJCC staging manual (8th edition) classifications. Results: A total of 4077 participants comprised the independent validation set with confirmed status (cancer: n = 2823; non-cancer: n = 1254 with non-cancer status confirmed at year-one follow-up). Sensitivity was reported for 24 cancer classes (sample sizes ranged from 10 to 524 participants), as well as an “other” cancer class (59 participants). According to AJCC classification, the MCED test was found to detect cancer signals across 50+ AJCC cancer types, including some types not present in the training set; some cancer types had limited representation. Conclusions: This MCED test that is nearing clinical availability and was evaluated in the third CCGA substudy detected cancer signals across 50+ AJCC cancer types. Reporting CCGA cancer classes and AJCC cancer types demonstrates the ability of the MCED test to detect cancer signals across a set of diverse cancer types representing a wide range of biologic characteristics, including cancer types that the classifier has not been trained on, and supports its use on a population-wide scale. Clinical trial information: NCT02889978.

Conjunctival Melanoma: Outcomes based on the American Joint Committee on Cancer Clinical Classification (8th Edition) of 425 Patients at a Single Ocular Oncology Center.

The aim of this study was to evaluate outcomes of conjunctiva melanoma based on the American Joint Committee on Cancer Classification (AJCC) 8th edition. Retrospective interventional case series. Outcomes analysis of 425 patients. In this analysis of 425 patients with conjunctival melanoma, there were 266 (63%) patients classified as T1, 75 (18%) as T2, 84 (20%) as T3, and 0 (0%) as T4. A comparison (T1 vs T2 vs T3) revealed that history of primary acquired melanosis was more common in T2 (81% vs 96% vs 81%; P = 0.01) and conjunctival nevus more common in T1 (20% vs 9% vs 11%; P = 0.03). Of 381 patients with follow-up (mean of 57.6 months), comparison revealed higher T category with increasing local recurrence/new tumor (30% vs 43% vs 49%; P = 0.004), increasing exenteration (3% vs 9% vs 28%; P < 0.001), increasing melanoma-related locoregional lymph node metastasis (2% vs 7% vs 12%; P = 0.001), increasing melanoma-related systemic metastasis (9% vs 25% vs 23%; P < 0.001), and increasing melanoma-related death (4% vs 12% vs 18%; P < 0.001). A comparison at 10 years revealed visual acuity loss of >3 lines (32% vs 42% vs 63%; P < 0.001), melanoma recurrence/new tumor (47% vs 70% vs 74%; P < 0.001), exenteration (4% vs 24% vs 46%; P < 0.001), melanoma-related locoregional lymph node metastasis (3% vs 13% vs 25%; P < 0.001), melanoma-related systemic metastasis (13% vs 45% vs 40%; P < 0.001), and melanoma-related death (8% vs 22% vs 37%; P < 0.001). Based on the AJCC 8th edition of conjunctival melanoma, the 10-year risk per T category significantly increased for visual acuity loss of >3 lines, recurrence/new tumor, exenteration, locoregional and systemic melanoma-related metastasis, and melanoma-related death.

Differences in cutaneous melanoma survival between the 7th and 8th edition of the American Joint Committee on Cancer (AJCC). A multicentric population-based study.

The 8th edition of the AJCC manual for melanoma includes many changes leading to major substage migrations, which could lead to important clinical reassessments. To evaluate the differences and prognostic value of the 8th AJCC classification in comparison with the 7th edition. Clinical and histopathological data were retrieved from five melanoma referral centers including 7815 melanoma patients diagnosed between January 1998 and December 2018. All patients were reclassified and compared using the 7th and 8th classifications of the AJCC. Sankey plots were used to evaluate the migration of patients between the different versions. The primary outcome was overall survival (OS), and curves based on the Kaplan-Meier method were used to investigate survival differences between the 7th and 8th editions. The number of patients classified as stages IB, IIIA, and IIIB decreased while the patients classified as stages IA and IIIC increased notably. Migration analysis showed that many patients in group I were understaged whereas a significant percentage of patients in group III were upstaged. Indirect OS analysis showed a loss in the linearity in the AJCC 8th edition and the groups tended to overlap. Direct OS analysis between groups and versions of the AJCC showed a better prognosis within the new stage III patients, with no effect on those in stages I and II. The 8th AJCC edition represents an important change in the classification of patients. We observe that the main migratory changes occur in stage I and III, that severity linearity is lost and groups overlap, and that a more advanced stage does not mean a worse prognosis.

Recombinant Interferon Alpha-2b as Primary Treatment for Ocular Surface Squamous Neoplasia.

Purpose:To investigate the effects of topical and perilesional interferon alpha-2b as primary treatment for ocular surface squamous neoplasia (OSSN).Methods:In this prospective interventional case series, topical interferon alpha-2b (3 MIU/mL) was used as the initial treatment of OSSN, with perilesional interferon alpha-2b (3 MIU/mL) added based on clinical response. The primary outcome was complete tumor resolution. Spearman's rank correlation test was used to investigate the association of complete tumor resolution and time to resolution with baseline tumor characteristics and the American Joint Committee on Cancer (AJCC) classification for OSSN.Results:Ninety-two patients (92 OSSN tumors) were included in the study. The total follow-up duration was 13.57 ± 2.14 months (median: 12, range: 3–23). The median basal tumor diameter was 4 mm (mean: 4.13 ± 1.37). Complete tumor resolution was achieved in 89 cases (96.73%), with a median time to complete tumor resolution of 5 months (mean: 4.64 ± 1.92). Complete tumor resolution was 57 of 57 in T1 (100%), 8 of 9 in T2 (88.88%), and 21 of 23 in T3 (91.30%). There were statistically significant correlations between AJCC classification and complete tumor resolution (Spearman's r = −0.22, P = 0.03) and maximal basal tumor diameter and the time to complete resolution (Spearman's r = 0.35, P = 0.001). There were no recurrences during the study follow-up period.Conclusion:Topical interferon alpha-2b is effective and well tolerated as a primary treatment for OSSN, with a high rate of tumors responding completely to therapy.

The age threshold of the 8th edition AJCC classification is useful for indicating patients with aggressive papillary thyroid cancer in clinical practice

BackgroundPapillary thyroid cancer (PTC) is unique among cancers in that patient age is a consideration in staging. One of the most important modifications in the 8th Edition of the American Joint Committee on Cancer (AJCC) classification is to increase the age cut off for risk stratification in PTC from 45 to 55 years. However, whether this cut off is useful in clinical practice remains controversial. In the present study, we assessed how well this new age threshold stratifies patients with aggressive PTC.MethodsWe retrospectively analyzed the clinicopathological features and overall survival rate of patients with PTC admitted to and surgically treated at a single surgical center. The study protocol was divided into two series. In each series all patients (n = 523) were divided in 2 groups according to age cut off. In the first series (cut off 45) patients < 45 (n = 193) vs. ≥45 (n = 330) were compared, and in the second series (cut off 55) patients < 55 (n = 306) vs. ≥55 (n = 217) were compared.ResultsThe rate of the prevalence of locally advanced disease (pT3 and pT4) was significantly higher in the patients above 55 years old than in those below 55 years old (p = 0.013). No significant differences were found for this parameter in series with cut off point 45 years old. A significantly higher risk of locally advanced disease T3 + T4 (OR = 4.87) and presence of LNM (N1) (OR = 3.78) was observed in ≥45 years old group (p = 0.021 and p < 0.0001, respectively). More expressive results were found for the patients ≥55 years old group, where the risk of locally advanced disease (T3 + T4) was higher (OR = 5.21) and LNM presence was OR = 4.76 (p < 0.001 and p < 0.0001, respectively). None of the patients below 55 years old showed distant metastasis, but 19 patients above 55 years old showed M1 (p < 0.0001). In older patients group (≥55 years old) we observed deaths related thyroid cancer in 11 individuals.ConclusionsThe age cut off of 55 years old for risk stratification proposed by the 8th Edition of AJCC effectively stratifies PTC patients with a poor prognosis, indicating it is likely to be useful in clinical practice.

Compartmental Surgery With Microvascular Free Flap Reconstruction in Patients With T1-T4 Squamous Cell Carcinoma of the Tongue: Analysis of Risk Factors, and Prognostic Value of the 8th Edition AJCC TNM Staging System.

Compartmental surgery and primary reconstruction with microvascular free flaps represent the gold-standard in the treatment of oral tongue squamous cell carcinoma (OTSCC). However, there are still unclear clinical features that negatively affect the outcomes. This retrospective study included 80 consecutive patients with OTSCC who underwent compartmental surgery and primary reconstruction by free flap. The oncologic outcomes, the reliability of the 8th edition American Joint Committee on Cancer (AJCC) staging system and the prognostic factors were evaluated. Fifty-nine males and 21 females (mean age 57.8 years, range 27–81 years) were treated between November 2010 and March 2018 (one patient had two metachronous primaries). Seventy-one patients (88.75%, 52 males, 19 females, mean age of 57.9 years, range of 27–81 years) had no clinical history of previous head and neck radiotherapy and were considered as naive. Histology showed radical surgery on 80/81 lesions (98.8%), with excision margins >0.5 cm, while in 1 case (1.2%), a close posterior margin was found. According to the 8th AJCC classification, 37 patients (45.7%) were upstaged shifting from the clinical to the pathological stage, and 39 (48.1%) showed an upstaging while shifting from the 7th to the 8th AJCC staging system (no tumors were downstaged). Nodal involvement was confirmed in 33 patients (40.7%). Perineural and lymphovascular invasion were present in 9 (11.1%) and 11 (13.6%) cases, respectively. Twenty-two patients (27.1%) underwent adjuvant therapy. The 5-years disease-specific, overall, overall relapse-free, locoregional relapse-free and distant metastasis-free survival rates were 73.2, 66.8, 62.6, 67.4, and 86%, respectively. Patients with a lymph node ratio >0.09 experienced significantly worse outcomes. Univariate analysis showed that patients with previous radiotherapy, stage IV disease, nodal involvement, and lymphovascular invasion had significantly worse outcomes. Multivariate analysis focused naive patients and showed that lymphovascular invasion, advanced stage of disease, and node involvement resulted reliable prognostic factors, and patients with the same tumor stage and histological risk factors who did not undergo adjuvant therapy experienced significantly worse outcomes. In our series, surgery played a major role in the treatment of local extension; adjuvant therapy resulted strictly indicated in patients with advanced-stage disease associated with risk factors.

Enucleated globes with choroidal melanoma: A retrospective histopathological study and correlation with cytogenetic profile in 2 eye centers

BackgroundUveal melanoma is the commonest intraocular malignant tumor in adults and the choroid is the commonest involved location. It is more prevalent in Caucasians; however, the demographics are widely variable based on ethnicity. Histopathological features have been correlated to the cytogenetic profile, which we intend to report through the study of enucleated eyes with choroidal melanoma (CM). Materials and MethodsA retrospective review of 28 enucleated globes with CM in 2 tertiary eye centers (January 2000-December 2017). The tumors were histopathologically classified based on the 8th edition of the American Joint Committee on Cancer (AJCC). The histopathological risk factors and the AJCC classifications were correlated with Fluorescence in situ hybridization (FISH) for chromosomes 3 and 8 available results in 18/28 eyes. ResultsWe have included 28 patients with a mean age of 56 years, 13 males (46.4%) and 15 females (53.6%). None had lymph node involvement or metastatic disease. The tumor size was categorized as 3 and 4 in 68% of eyes. Half tumors were of spindle cell type and were associated with absent cytogenetic abnormality in chromosomes 3 and 8 (P=0.005). Closed vascular loops presence was significantly associated with abnormal chromosomes 3 and 8 (P=0.027). ConclusionPatients in our area presented late with larger tumor size. The spindle cell CM was the commonest and correlated with negative FISH results, while the presence of closed vascular loops was a risk factor for abnormal FISH results hence expected worse prognosis. AJCC classification did not correlate well with our FISH results.

Validation and modification of staging Systems for Poorly Differentiated Pancreatic Neuroendocrine Carcinoma

BackgroundThe American Joint Committee on Cancer (AJCC) and the European Neuroendocrine Tumor Society (ENETS) staging classifications are two broadly used systems for pancreatic neuroendocrine tumors. This study aims to identify the most accurate and useful tumor–node–metastasis (TNM) staging system for poorly differentiated pancreatic neuroendocrine carcinomas (pNECs).MethodsAn analysis was performed to evaluate the application of the ENETS, 7th edition (7th) AJCC and 8th edition (8th) AJCC staging classifications using the Surveillance, Epidemiology, and End Results (SEER) registry (N = 568 patients), and a modified system based on the analysis of the 7th AJCC classification was proposed.ResultsIn multivariable analyses, only the 7th AJCC staging system allocated patients into four different risk groups, although there was no significant difference. We modified the staging classification by maintaining the T and M definitions of the 7th AJCC staging and adopting new staging definitions. An increased hazard ratio (HR) of death was also observed from class I to class IV for the modified 7th (m7th) staging system (compared with stage I disease; HR for stage II =1.23, 95% confidence interval (CI) = 0.73–2.06, P = 0.44; HR for stage III =2.20, 95% CI =1.06–4.56, P = 0.03; HR for stage IV =4.95, 95% CI =3.20–7.65, P < 0.001). The concordance index (C-index) was higher for local disease with the m7th AJCC staging system than with the 7th AJCC staging system.ConclusionsThe m7th AJCC staging system for pNECs proposed in this study provides improvements and may be assessed for potential adoption in the next edition.

Accuracy of The Cancer Genome Atlas Classification vs American Joint Committee on Cancer Classification for Prediction of Metastasis in Patients With Uveal Melanoma

The Cancer Genome Atlas (TCGA) classification is a newly emerging method for prediction of uveal melanoma (UM)-related metastasis and death. Limited information is available regarding the accuracy of the TCGA classification for prediction of metastasis in patients with UM. To investigate the accuracy of the TCGA classification for predicting UM-related metastasis compared with the American Joint Committee on Cancer (AJCC) classification. In this retrospective cohort study, patients with UM treated with plaque radiotherapy at a tertiary referral center from October 1, 2008, to December 31, 2018, were evaluated. All patients with tumors classified according to the American Joint Committee on Cancer Staging Manual, 8th Edition, and who completed pretreatment fine-needle aspiration biopsy sampling for genetic analysis of chromosomes 3 and 8 for TCGA classification were included. Tumors were classified into 4 categories, 17 subcategories, and 4 stages using AJCC classification and further grouped into 4 classes using TCGA classification. Value of TCGA classification vs AJCC classification for predicting UM-related metastasis. Of 642 included patients, 331 (51.6%) were women, and the mean (SD) age was 58.0 (13.8) years. There were 642 tumors from 642 patients classified according to both AJCC and TCGA classifications. The mean (range) follow-up time for the entire cohort was 43.7 (1.4-159.2) months. At 5 years, TCGA classification showed higher value for prediction of metastasis (4 TCGA classes: Wald statistic, 94.8; hazard ratio [HR], 2.8; 95% CI, 2.3-3.5; P < .001; 4 AJCC categories: Wald statistic, 67.5; HR, 2.6; 95% CI, 2.1-3.2; P < .001; 17 AJCC subcategories: Wald statistic, 74.3; HR, 1.3; 95% CI, 1.2-1.3; P < .001; 4 AJCC stages: Wald statistic, 67.0; HR, not applicable; P < .001). After entering TCGA and AJCC classifications into a multivariate model, TCGA classification still showed higher value for prediction of metastasis (TCGA classification: Wald statistic, 61.5; HR, 2.4; 95% CI, 1.9-2.9; P < .001; AJCC classification: Wald statistic, 35.5; HR, 1.9; 95% CI, 1.5-2.4; P < .001). These results suggest that TCGA classification provides accuracy that is superior to AJCC categories, subcategories, and stages for predicting metastasis from UM. When genetic testing is available, TCGA classification can provide a more accurate way to identify patients at high risk of metastasis who might benefit from adjuvant therapy.

Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†.

Cutaneous melanoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†.

Prognostic Performance of Preoperative Staging: Assessed by Using Multidetector Computed Tomography-Between the New Clinical Classification and the Pathological Classification in the Eighth American Joint Committee on Cancer Classification for Gastric Carcinoma.

Since the eighth American Joint Committee on Cancer (AJCC) classification recently introduced the clinical classification for preoperative staging of gastric cancer, the new clinical classification has not been extensively validated yet. Therefore, in this study, we compared the prognostic performance of the new clinical classification and the pathologic classification for preoperative staging of gastric cancer. We reviewed 3027 patients with gastric cancer who were surgically treated between 2009 and 2013. Patient survival was analyzed according to the preoperative stage by the clinical classification and the pathologic classification in the eighth AJCC classification. The prognostic performance was examined using the Akaike information criterion (AIC) value and Harrell c-index. Patient survival was significantly different across the different stages when both classifications were used. However, individual pairwise comparisons showed that survival differences between each stage were more distinctive and homogeneous in the pathologic classification. In the multivariate model adjusted for the final pathologic stage, preoperative staging by the pathologic classification was an independent prognostic factor, whereas the clinical classification was not. The pathologic classification showed a lower AIC value compared with the clinical classification (5100.64 vs. 5114.14). The Harrell c-index was higher in the pathologic classification than in the clinical classification (0.741 vs. 0.739). The new clinical classification in the eighth AJCC classification discriminates patient survival well. However, it does not appear to have a better prognostic performance compared with the pathologic classification for preoperative staging of gastric cancer.