Validation of the Prognostic Stage of American Joint Committee on Cancer Eighth Edition Staging Manual in Invasive Lobular Carcinoma Compared to Invasive Ductal Carcinoma and Proposal of a Novel Score System
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SUBMITTER: Ding S
PROVIDER: S-EPMC7461987 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe American Joint Committee on Cancer (AJCC) maintains that the eighth edition of its Staging Manual (AJCC8) has improved accuracy compared with the seventh (AJCC7). However, there are concerns that implementation may disrupt analysis of active clinical trials for stage III patients. We used an independent cohort of melanoma patients to test the extent to which AJCC8 has improved prognostic accuracy compared with AJCC7.MethodsWe analyzed a cohort of 1315 prospectively enrolled patients. We assessed primary tumor and nodal classification of stage I-III patients using AJCC7 and AJCC8 to assign disease stages at diagnosis. We compared recurrence-free (RFS) and overall survival (OS) using Kaplan-Meier curves and log-rank tests. We then compared concordance indices of discriminatory prognostic ability and area under the curve of 5-year survival to predict RFS and OS. All statistical tests were two-sided.ResultsStage IIC patients continued to have worse outcomes than stage IIIA patients, with a 5-year RFS of 26.5% (95% confidence interval [CI] = 12.8% to 55.1%) vs 56.0% (95% CI = 37.0% to 84.7%) by AJCC8 (P = .002). For stage I, removing mitotic index as a T classification factor decreased its prognostic value, although not statistically significantly (RFS concordance index [C-index] = 0.63, 95% CI = 0.56 to 0.69; to 0.56, 95% CI = 0.49 to 0.63, P = .07; OS C-index = 0.48, 95% CI = 0.38 to 0.58; to 0.48, 95% CI = 0.41 to 0.56, P = .90). For stage II, prognostication remained constant (RFS C-index = 0.65, 95% CI = 0.57 to 0.72; OS C-index = 0.61, 95% CI = 0.50 to 0.72), and for stage III, AJCC8 yielded statistically significantly enhanced prognostication for RFS (C-index = 0.65, 95% CI = 0.60 to 0.70; to 0.70, 95% CI = 0.66 to 0.75, P = .01).ConclusionsCompared with AJCC7, we demonstrate that AJCC8 enables more accurate prognosis for patients with stage III melanoma. Restaging a large cohort of patients can enhance the analysis of active clinical trials.
| S-EPMC7492758 | biostudies-literature
Project description:Answer questions and earn CME/CNE To update the melanoma staging system of the American Joint Committee on Cancer (AJCC) a large database was assembled comprising >46,000 patients from 10 centers worldwide with stages I, II, and III melanoma diagnosed since 1998. Based on analyses of this new database, the existing seventh edition AJCC stage IV database, and contemporary clinical trial data, the AJCC Melanoma Expert Panel introduced several important changes to the Tumor, Nodes, Metastasis (TNM) classification and stage grouping criteria. Key changes in the eighth edition AJCC Cancer Staging Manual include: 1) tumor thickness measurements to be recorded to the nearest 0.1 mm, not 0.01 mm; 2) definitions of T1a and T1b are revised (T1a, <0.8 mm without ulceration; T1b, 0.8-1.0 mm with or without ulceration or <0.8 mm with ulceration), with mitotic rate no longer a T category criterion; 3) pathological (but not clinical) stage IA is revised to include T1b N0 M0 (formerly pathologic stage IB); 4) the N category descriptors "microscopic" and "macroscopic" for regional node metastasis are redefined as "clinically occult" and "clinically apparent"; 5) prognostic stage III groupings are based on N category criteria and T category criteria (ie, primary tumor thickness and ulceration) and increased from 3 to 4 subgroups (stages IIIA-IIID); 6) definitions of N subcategories are revised, with the presence of microsatellites, satellites, or in-transit metastases now categorized as N1c, N2c, or N3c based on the number of tumor-involved regional lymph nodes, if any; 7) descriptors are added to each M1 subcategory designation for lactate dehydrogenase (LDH) level (LDH elevation no longer upstages to M1c); and 8) a new M1d designation is added for central nervous system metastases. This evidence-based revision of the AJCC melanoma staging system will guide patient treatment, provide better prognostic estimates, and refine stratification of patients entering clinical trials. CA Cancer J Clin 2017;67:472-492. © 2017 American Cancer Society.
| S-EPMC5978683 | biostudies-literature
Project description:ImportanceTo our knowledge, there are no validation studies to date of the prognostic value of the AJCC Cancer Staging Manual, eighth edition (AJCC 8), criteria for eyelid and periocular squamous cell carcinoma.ObjectiveTo determine the association of tumor (T) category in AJCC 8 with local recurrence, nodal metastasis, distant metastasis, and disease-specific survival (DSS) for eyelid and periocular squamous cell carcinoma.Design, setting, and participantsIn this retrospective, single-center cohort study, 109 consecutive patients with eyelid and periocular squamous cell carcinoma treated from January 1999 to April 2018 were included. Patients with secondary involvement of the periocular region were excluded.Main outcomes and measuresLocal recurrence, nodal metastasis, distance metastasis, and DSS.ResultsOf the 109 included patients, 81 (74.3%) were male, and the median (range) age was 66 (40-91) years. At presentation, 43 patients (39.4%) had recurrent tumor, 4 (3.7%) had nodal metastasis, and 1 (0.9%) had distant metastasis. The median (range) follow-up was 23 (1-161) months. During follow-up, 11 patients (10.1%) developed local recurrence, 7 (6.4%) developed nodal metastasis, 2 (1.8%) developed distant metastasis, and 9 (8.3%) died of disease. The 5-year DSS rate was 87.7% (95% CI, 79.5-96.9). Chronic immunosuppression (hazard ratio, 47.24; 95% CI, 7.33-304.30; P < .001) and presentation with recurrent squamous cell carcinoma (hazard ratio, 5.22; 95% CI, 1.12-24.31; P = .04) were associated with local recurrence during follow-up. Of the 11 patients with local recurrence during follow-up, 7 (64%) had perineural invasion. T category was associated with nodal metastasis; clinical stage of T2c or worse at presentation was associated with higher risk of nodal metastasis and death of disease but not with a higher risk of local recurrence. Distant metastasis was associated with nodal metastasis at presentation (hazard ratio, 32.50; 95% CI, 1.97-536.40; P = .02) and during follow-up. A total of 33 patients (30.3%) had different T categories depending on whether disease was staged according to the seventh or eighth edition of the AJCC Cancer Staging Manual. Compared with AJCC 7, AJCC 8 showed a better predictive value in terms of local recurrence (T3, 17% vs 14%; T4, 11% vs 16%) and DSS.Conclusions and relevanceThese findings suggest that T category in AJCC 8 is associated with nodal metastasis and DSS. Immunosuppression and presentation with recurrent disease are associated with increased risk of future local recurrence. Patients with tumors of clinical stage T2c or worse at presentation are at increased risk of nodal metastasis and worse DSS and should undergo surveillance for nodal metastasis. Future studies, ideally prospective in design, could provide greater confidence in these findings.
| S-EPMC6512305 | biostudies-literature
Project description:ImportanceImmune checkpoint inhibitors (ICIs) have transformed the survival of patients with metastatic melanoma. Patient prognosis is reflected by the American Joint Committee on Cancer (AJCC) staging system; however, it is unknown whether the metastatic (M) stage categories for cutaneous melanoma remain informative of prognosis in patients who have received ICIs.ObjectivesTo evaluate the outcomes of patients with metastatic cutaneous melanoma based on the M stage category from the AJCC eighth edition and to determine whether these designations continue to inform the prognosis of patients who have received ICIs.Design, setting, and participantsThis cohort study included patients with metastatic cutaneous melanoma who were treated between August 2006 and August 2019 at the University of Michigan. The estimated median follow-up time was 35.5 months. Patient data were collected via the electronic medical record system. Critical findings were externally validated in a multicenter nationwide cohort of patients treated within the Veterans Affairs health care system. Data analysis was conducted from February 2020 to January 2021.ExposuresAll patients were treated with dual-agent concurrent ipilimumab and nivolumab followed by maintenance nivolumab or single-agent ipilimumab, nivolumab, or pembrolizumab therapy. Patients were staged using the AJCC eighth edition.Main outcomes and measuresUnivariable and multivariable analyses were used to assess the prognostic value of predefined clinicopathologic baseline factors on survival.ResultsIn a discovery cohort of 357 patients (mean [SD] age, 62.6 [14.2] years; 254 [71.1%] men) with metastatic cutaneous melanoma treated with ICIs, the M category in the AJCC eighth edition showed limited prognostic stratification by both univariable and multivariable analyses. The presence of liver metastases and elevated levels of serum lactate dehydrogenase (LDH) offered superior prognostic separation compared with the M category (liver metastases: hazard ratio, 2.22; 95% CI, 1.48-3.33; P < .001; elevated serum LDH: hazard ratio, 1.73; 95% CI, 1.16-2.58; P = .007). An updated staging system based on these factors was externally validated in a cohort of 652 patients (mean [SD] age, 67.9 [11.6] years; 630 [96.6%] men), with patients without liver metastases or elevated LDH levels having the longest survival (median overall survival, 30.7 months).Conclusions and relevanceThis study found that the AJCC eighth edition M category was poorly reflective of prognosis in patients receiving ICIs. Future staging systems could consider emphasizing the presence of liver metastases and elevated LDH levels. Additional studies are needed to confirm the importance of these and other prognostic biomarkers.
| S-EPMC7944385 | biostudies-literature
Project description:Invasive lobular breast cancer (ILC) accounts for 10-15% of breast cancers and has distinct characteristics compared with the more common invasive ductal carcinoma (IDC). Studies have shown that ILC may be less sensitive to chemotherapy than IDC, with lower rates of complete pathological response after neo-adjuvant chemotherapy, but it is not clear how this affects long-term survival. Patients at Guy's and St Thomas' NHS Foundation Trust between 1975 and 2016 diagnosed with ER+ IDC or ER+ ILC were eligible for inclusion. Kaplan-Meier plots and Cox proportional-hazards regression models were used for analysis. There was no difference in overall survival comparing ER+ ILC to ER+ IDC (OR: 0.94, 95% CI: 0.83, 1.04) with a median follow-up time of 8.3 years compared to 8.4 years in IDC. However, ER+HER2- ILC had worse survival compared to ER+HER2- IDC in those that received chemotherapy (OR: 1.46, 95% CI: 1.06, 2.01). Here, median follow-up time was 7.0 years in ILC compared to 8.1 years in IDC. These results indicate worse overall survival after chemotherapy (neo-adjuvant and adjuvant) in ILC compared to ER+HER2- IDC even when correcting for tumour grade, age, size, and nodal involvement, but validation is needed in a larger study population.
| S-EPMC8234044 | biostudies-literature
Project description:ImportanceThe recently released eighth edition of the American Joint Committee on Cancer TNM staging system for pancreatic cancer seeks to improve prognostic accuracy but lacks international validation.ObjectiveTo validate the eighth edition of the American Joint Committee on Cancer TNM staging system in an international cohort of patients with resected pancreatic ductal adenocarcinoma.Design, setting, and participantsThis international multicenter cohort study took place in 5 tertiary centers in Europe and the United States from 2000 to 2015. Patients who underwent pancreatoduodenectomy for nonmetastatic pancreatic ductal adenocarcinoma were eligible. Data analysis took place from December 2017 to April 2018.ExposuresPatients were retrospectively staged according to the seventh and eighth editions of the TNM staging system.Main outcomes and measuresPrognostic accuracy on survival rates, assessed by Kaplan-Meier and multivariate Cox proportional hazards analyses and concordance statistics.ResultsA total of 1525 consecutive patients were included (median [IQR] age, 66 (58-72) years; 802 (52.6%) male). Distribution among stages via the seventh edition was stage IA in 41 patients (2.7%), stage IB in 42 (2.8%), stage IIA in 200 (13.1%), stage IIB in 1229 (80.6%), and stage III in 12 (0.8%); this changed with use of the eighth edition to stage IA in 118 patients (7.7%), stage IB in 144 (9.4%), stage IIA in 22 (1.4%), stage IIB in 643 (42.2%), and stage III in 598 (39.2%). With the eighth edition, 774 patients (50.8%) migrated to a different stage; 183 (12.0%) were reclassified to a lower stage and 591 (38.8%) to a higher stage. Median overall survival for the entire cohort was 24.4 months (95% CI, 23.4-26.2 months). On Kaplan-Meier analysis, 5-year survival rates changed from 38.2% for patients in stage IA, 34.7% in IB, 35.3% in IIA, 16.5% in IIB, and 0% in stage III (log-rank P < .001) via classification with the seventh edition to 39.2% for patients in stage IA, 33.9% in IB, 27.6% in IIA, 21.0% in IIB, and 10.8% in stage III (log-rank P < .001) with the eighth edition. For patients who were node negative, the T stage was not associated with prognostication of survival in either edition. In the eighth edition, the N stage was associated with 5-year survival rates of 35.6% in N0, 20.8% in N1, and 10.9% in N2 (log-rank P < .001). The C statistic improved from 0.55 (95% CI, 0.53-0.57) for the seventh edition to 0.57 (95% CI, 0.55-0.60) for the eighth edition.Conclusions and relevanceThe eighth edition of the TNM staging system demonstrated a more equal distribution among stages and a modestly increased prognostic accuracy in patients with resected pancreatic ductal adenocarcinoma compared with the seventh edition. The revised T stage remains poorly associated with survival, whereas the revised N stage is highly prognostic.
| S-EPMC6583013 | biostudies-literature
Project description:Objective: To validate the eighth edition of the AJCC staging system in patients with pancreatic adenocarcinoma receiving only stereotactic body radiation therapy and chemotherapy, and to propose modifications to improve prognostic accuracy. Methods: Patients with pathologically confirmed pancreatic adenocarcinoma without metastasis who were undergoing only chemoradiotherapy were included and staged according to the seventh and eighth editions of the AJCC staging system. Meanwhile, another group of stage T4 patients from the above enrollment with only portal vein involvement with or without tumor thrombi (PV ± PVTT) were retrieved for survival comparisons. Modifications were proposed according to the survival comparisons. A cohort from the SEER database was used for external validation of the modified staging system. Results: A total of 683 patients were included. Patients with N2 or N1 but different T stages had significantly different survival outcomes according to the eighth edition. The survival of patients with PV ± PVTT was comparable to that of patients with T4 tumors. The concordance index of the seventh and eighth editions, and the modified staging system was 0.744 (95%CI: 0.718-0.769), 0.750 (95%CI: 0.725-0.775), and 0.788 (95%CI: 0.762-0.813), respectively. For external validation, the concordance index was 0.744 (95%CI: 0.718-0.770), 0.750 (95%CI: 0.724-0.776), and 0.788 (95%CI: 0.762-0.814), respectively. Conclusions: The modified staging system is suggested to have the most accurate prognostic value. Hence, PV ± PVTT should be added to the definition of T4 tumors regardless of tumor size. Patients with N2 or N1 in different T stages could be regrouped into different substages. Additionally, stage III should be subclassified into IIIA (T3N2 and T4N0) and IIIB (T4N1-2).
| S-EPMC7309473 | biostudies-literature
Project description:We comparatively investigated the expression and clinical implications of lipid metabolism-related proteins in invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) of the breast. A total of 584 breast cancers (108 ILC and 476 IDC) were subjected to tissue microarray and immunohistochemical analysis for lipid metabolism-related proteins including hormone-sensitive lipase (HSL), perilipin A, fatty acid binding protein (FABP)4, carnitine palmitoyltransferase (CPT)-1, acyl-CoA oxidase 1, and fatty acid synthetase (FASN). HSL, perilipin A, and FABP4 expression (all p < 0.001) differed significantly: HSL and FABP4 were more frequently present in ILC, whereas perilipin A was more frequently detected in IDC. Among all invasive cancers, HSL and FABP4 were highly expressed in luminal A-type ILC (p < 0.001) and perilipin A in luminal A-type IDC (p = 0.007). Among luminal B-type cancers, HSL and FABP4 were more highly expressed in ILC (p < 0.001). Univariate analysis found associations of shorter disease-free survival with CPT-1 positivity (p = 0.004) and acyl-CoA oxidase 1 positivity (p = 0.032) and of shorter overall survival with acyl-CoA oxidase 1 positivity (p = 0.027). In conclusion, ILC and IDC exhibited different immunohistochemical lipid metabolism-related protein expression profiles. Notably, ILC exhibited high HSL and FABP4 and low perilipin A expression.
| S-EPMC5297861 | biostudies-literature
Project description:Breast cancer is a malignant neoplasm originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. ILCs and IDCs vary from each other with respect to various histological, biological and clinical features. Remarkably, ductal tumors tending to form glandular structures, whereas lobular tumors are less cohesive and tends to invade in single file. The high degree of similarity in the prognoses of IDC and ILC makes it beneficial to develop a differential diagnostic protocol to classify the two conditions. The main goal of the study is to construct the genetic regulatory network from the microarray data using biological knowledge and constraint-based inferences, in order to explore the potential significant gene regulatory networks that can differentiate IDC and ILC and thereby understand the complex interactions that are influenced by the genetic networks. Out of the 54676 genes present on the GPL570 platform- 29 genes exhibited 4 fold up regulation in case of IDC and 22 in the case of ILC. The ductal and lobular tumors displayed a striking difference in the expression of genes associated with cell adhesion, protein folding, and protein phosphorylation and invasion. Construction of separate gene regulation networks for IDC and ILC on the basis of gene expression altercation can be utilized in understanding the distinction in the possible mechanism that underlies the pathological differences between the two, which can be exploited in identifying diagnostic or therapeutic targets.
| S-EPMC3346022 | biostudies-literature
Project description:ObjectivesThe ground-glass component of part-solid tumour (PST) was eliminated as a clinical T (cT) descriptor in the eighth edition of the tumour, node and metastasis (TNM) staging system. We aimed to validate the new cT descriptor and investigate the prognostic impact of PST in the new staging system.MethodsNon-small-cell lung cancer (NSCLC) patients (n = 1061) who underwent lung resection and were available for the assessment of thin-section computed tomography images were retrospectively reviewed. Tumours with a solid component (SC) size-to-whole tumour size (STR) ratio of 0, those with 0 < STR < 1 and those with an STR of 1 were defined as pure ground-glass tumours, PSTs and solid tumours (STs), respectively.ResultsTumours with an SC diameter of >30 mm were less frequently observed among PSTs than among STs (4.83% vs 32.6%, P < 0.001). The postoperative 5-year survival of NSCLC patients with ground-glass tumour, PST and ST was 97.6%, 89.0% and 76.3%, respectively. In the survival analysis of patients with an SC diameter ≤30 mm, significant differences were observed among PST and ST (5-year survival, 90.7% vs 74.6%, P < 0.001). The multivariable analysis showed that age <70 years old, female sex, procedures with a lobectomy or more, SC size, pN0 disease and PST were independent predictors of a better survival among all PST and ST patients.ConclusionsAmong patients with cT1 tumours, those with PST showed a significantly better survival than did those with ST. Small-sized PST tumours may not be suitable for the new cT descriptor.
| S-EPMC8766204 | biostudies-literature