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Concept: Ann Arbor staging

171

Over the past decades, many studies have used data mining technology to predict the 5-year survival rate of colorectal cancer, but there have been few reports that compared multiple data mining algorithms to the TNM classification of malignant tumors (TNM) staging system using a dataset in which the training and testing data were from different sources. Here we compared nine data mining algorithms to the TNM staging system for colorectal survival analysis.

Concepts: Cancer, Oncology, Carcinoma in situ, Cancer staging, Colorectal cancer, Survival rate, TNM staging system, Ann Arbor staging

157

Answer questions and earn CME/CNE The revision of the eighth edition of the primary tumor, lymph node, and metastasis (TNM) classification of the American Joint Commission of Cancer (AJCC) for breast cancer was determined by a multidisciplinary team of breast cancer experts. The panel recognized the need to incorporate biologic factors, such as tumor grade, proliferation rate, estrogen and progesterone receptor expression, human epidermal growth factor 2 (HER2) expression, and gene expression prognostic panels into the staging system. AJCC levels of evidence and guidelines for all tumor types were followed as much as possible. The panel felt that, to maintain worldwide value, the tumor staging system should remain based on TNM anatomic factors. However, the recognition of the prognostic influence of grade, hormone receptor expression, and HER2 amplification mandated their inclusion into the staging system. The value of commercially available, gene-based assays was acknowledged and prognostic input added. Tumor biomarkers and low Oncotype DX recurrence scores can alter prognosis and stage. These updates are expected to provide additional precision and flexibility to the staging system and were based on the extent of published information and analysis of large, as yet unpublished databases. The eighth edition of the AJCC TNM staging system, thus, provides a flexible platform for prognostic classification based on traditional anatomic factors, which can be modified and enhanced using patient biomarkers and multifactorial prognostic panel data. The eighth edition remains the worldwide basis for breast cancer staging and will incorporate future online updates to remain timely and relevant. CA Cancer J Clin 2017. © 2017 American Cancer Society.

Concepts: Cancer, Breast cancer, Carcinoma in situ, Lung cancer, Cancer staging, Lymph node, TNM staging system, Ann Arbor staging

28

Background. The 7th TNM staging system for non-small cell lung cancer (NSCLC) developed by the International Association for the study of Lung Cancer (IASLC) has been applied in Sweden since the beginning of the year 2010. The aim of this retrospective study was to evaluate the prognostic role of the 7th TNM staging system in a surgical Swedish patient cohort with node-negative NSCLC. Material and methods. We collected data from stage I patients (pT1-2 pN0, 6th TNM system) who underwent surgery for NSCLC at Karolinska University Hospital from 1987 to 2002. Tumors were restaged according to the 7th TNM version. Cox multivariate survival analysis was implemented in order to determine the prognostic impact of pathological stage when classified according to either the 6th or the 7th TNM systems. Results. The patient population consisted of 452 subjects. Tumor size was ≤ 3 cm in 51% of cases. The predominant histology was adenocarcinoma (53%) and lobectomy was the most common surgical procedure (82% of patients). The five-year survival rate in patients with stage IA vs. IB (6th TNM) was 62% vs. 51%, respectively (log-rank p = 0.036). Corresponding figures for the 7th TNM system were 70% in stage IA-T1a, 51% in stage IA-T1b, 54% in stage IB, 51% in stage IIA and 35% in stage IIB (log-rank p = 0.002). On multivariate analysis, adjusted by age, gender, histology, kind of surgery, grade of differentiation and smoking status, pathological stage was an independent prognostic factor if classified according to the 7th TNM version (p = 0.001), but not if scored according to the 6th TNM edition (p = 0.090). Conclusion. The 7th TNM classification system is a more accurate predictor of prognosis in stage I operated patients than the old classification. The new system should be implemented even on retrospective cohorts especially when investigating the prognostic implication of the expression of molecular biomarkers.

Concepts: Cancer, Carcinoma in situ, Lung cancer, Non-small cell lung carcinoma, Cancer staging, Hospital, TNM staging system, Ann Arbor staging

27

Appendiceal neuroendocrine neoplasms (NENs) are rare and usually incidentally discovered. Most cases are clinically indolent, although the rare aggressive ones are poorly predictable. The aim of this study was to test the applicability and prognostic significance of the new World Health Organization (WHO) classification and to test the several pathologic features and TNM staging systems (American Joint Committee on Cancer and European Neuroendocrine Tumor Society) in these tumors. A multi-institutional retrospective series of 138 appendiceal NENs was selected on the basis of the availability of both pathologic material and clinical information, including follow-up data. All cases were reviewed to record pathologic features and to apply year 2000 and 2010 WHO classifications, as well as European Neuroendocrine Tumor Society and American Joint Committee on Cancer TNM stages. Clinical and pathologic characteristics were compared with disease outcome by contingency, univariate, and multivariate survival analyses. Although up to one third of cases presented several malignancy-associated pathologic features, only 4 patients died of the disease. Adverse outcome was significantly associated with extramural extension (including mesoappendix), well-differentiated carcinoma diagnosis (2000 WHO classification), pT3-4 stage, older age, and presence of positive resection margins, but not with tumor size, mitotic or proliferative indexes, and, consequently, 2010 WHO grading. In the appendix, at variance with midgut/hindgut NENs, the 2000 WHO classification performs better than the grading-based 2010 WHO scheme and, together with tumor stage, is the most relevant parameter associated with clinical aggressiveness.

Concepts: Cancer, Oncology, Carcinoma in situ, Lung cancer, Cancer staging, Neuroendocrine tumor, TNM staging system, Ann Arbor staging

23

Patients with human papillomavirus (HPV)-related oropharyngeal cancer (OPC) generally present with more advanced disease but have better survival than patients with HPV-unrelated OPC. The current American Joint Commission on Cancer (AJCC)/Union for International Cancer Control (UICC) TNM staging system for OPC was developed for HPV-unrelated OPC. A new staging system is needed to adequately predict outcomes of patients with HPV-related OPC.

Concepts: Cancer, Human papillomavirus, Carcinoma in situ, Lung cancer, Cancer staging, Nasopharyngeal carcinoma, TNM staging system, Ann Arbor staging

4

Studies in classical Hodgkin lymphoma (cHL) typically measure the time to events from diagnosis. We evaluated the risk of relapse at event-free survival time points in cHL and compared the risk of death to expected mortality rates in British Columbia (BC).

Concepts: Mortality rate, Demography, Lymphoma, Hodgkin's lymphoma, Non-Hodgkin lymphoma, British Columbia, Ann Arbor staging, Thomas Hodgkin

3

JAK2 constitutive activation/overexpression is common in classical Hodgkin lymphoma, and several cytokines stimulate Hodgkin lymphoma cells by recognizing JAK1-/JAK2-bound receptors. JAK blockade may thus be therapeutically beneficial in HL. This Phase II study assessed the safety and efficacy of ruxolitinib, an oral JAK1/2 inhibitor, in relapsed/refractory Hodgkin lymphoma patients. The primary objective was overall response rate according to IHP 2007 criteria. Thirty-three advanced patients (median prior lines: 5; refractory: 82%) were included; nine (27.3%) received at least 6 cycles of ruxolitinib and six (18.2%) > 6 cycles therapy. The overall response rate after 6 cycles was 3/32 (9.4%) patients, all partial responders, with transient stable disease in 11/32. Best overall response rate was 6/32 (18.8%). Rapid alleviation of B-symptoms was commonly noted. Median response duration was 7.7 months, median progression-free survival 3.5 months (95%CI: 1.9-4.6), and median overall survival 27.1 months (95%CI: 14.4-27.1). Forty adverse events were reported in 14/33 patients (42.4%); one led to treatment discontinuation; 87.5% recovered without sequelae. Twenty-five were of > Grade3. The latter consisted mostly of anemia (n=11) all considered related to ruxolitinib. Other main causes of > Grade3 adverse events included lymphopenia and infections. Of note, there was no Grade4 neutropenia or thrombocytopenia observed. Ruxolitinib shows signs of activity, though short-lived, beyond simple anti-inflammation. Its limited toxicity suggests the potential of being combined with other therapeutic modalities. ClinicalTrials.gov: NCT01877005.

Concepts: Clinical trial, Therapy, Lymphoma, Hodgkin's lymphoma, Blood disorders, Non-Hodgkin lymphoma, Ann Arbor staging, Thomas Hodgkin

2

Rhinoplasty is known to be one of the more technically challenging cosmetic procedures, with a revision rate of 5% to 15%. Reasons for revisions may range from minor deformities that can be treated in the office to major cosmetic and functional defects that require multiple surgical procedures to correct. The literature lacks a uniform scale that systematically evaluates the patient presenting for revision rhinoplasty. The TNM staging system for classifying malignant tumors was developed to aid the physician in planning treatment, providing some information about prognosis, assisting in evaluating the results of treatment, and facilitating the exchange of information. Although the patient presenting for a revision rhinoplasty does not have a potentially lethal disease, a classification system for such patients resembling that used for malignant tumors may provide similar benefits.

Concepts: Cancer, Carcinoma in situ, Cancer staging, Patient, TNM staging system, Ann Arbor staging

2

2

The outcomes of patients treated with surgery for early stage pancreatic ductal adenocarcinoma (PDAC) are variable with median survival ranging from 6 months to more than 5 years. This challenge underscores an unmet need for developing personalized medicine strategies to refine the current treatment decision-making process. To derive a prognostic gene signature for patients with early stage PDAC, a PDAC cohort from Moffitt Cancer Center (n = 63) was used with overall survival (OS) as the primary endpoint. This was further evaluated using an independent microarray cohort dataset (Stratford et al: n = 102). Technical validation was performed by NanoString platform. A prognostic 15-gene signature was developed and showed a statistically significant association with OS in the Moffitt cohort (hazard ratio [HR] = 3.26; p<0.001) and Stratford et al cohort (HR = 2.07; p = 0.02), and was independent of other prognostic variables. Moreover, integration of the signature with the TNM staging system improved risk prediction (p<0.01 in both cohorts). In addition, NanoString validation showed that the signature was robust with a high degree of reproducibility and the association with OS remained significant in the two cohorts. The gene signature could be a potential prognostic tool to allow risk-adapted stratification of PDAC patients into personalized treatment protocols; possibly improving the currently poor clinical outcomes of these patients.

Concepts: Scientific method, Statistics, Carcinoma in situ, Lung cancer, Cancer staging, Risk, TNM staging system, Ann Arbor staging