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Inter- and intra-observer variability in the classification of extracapsular extension in p16 positive oropharyngeal squamous cell carcinoma nodal metastases.

ABSTRACT: Discern inter- and intra-observer variability in the classification of extracapsular extension (ECE) in p16+ oropharyngeal (OP) SCC comparing pathologists' own criteria versus those of a well-defined classification system.Five pathologists reviewed 50 digitally scanned nodal metastasis slides in three Rounds. Round One was by their own criteria as ECE present or absent, and Rounds Two and Three were with a defined ECE system: Grade 0 (no ECE), 0c (no ECE - thick capsule; no infiltration), 1 (ECE - cells beyond capsule), and 2 (soft tissue metastasis - cells in soft tissue without residual node). Round Three assessed intra-observer variability after an 8 month washout period.In Round One, all five agreed on only 48% of cases (n=24). Fleiss's Kappa value was 0.508 (95% CI: 0.357-0.644). For Rounds Two and Three, Grades 0 and 0c and Grades 1 and 2 were separately grouped as ECE absent or present. In Round Two, all five agreed on 68% of cases (n=34). Fleiss' Kappa was 0.635 (95% CI: 0.472-0.783), indicating statistically significantly better agreement. In Round Three, all five agreed on 64% of cases (n=32) giving a Fleiss's Kappa of 0.639. Pathologists agreed with their prior reads in approximately 90% of cases (average n=45.4, range n=42-49), an average intra-observer Cohen's Kappa of 0.8 (range: 0.68-0.95). Inter- and intra-observer variability rates for classification of soft tissue metastasis (ECE2) were substantially worse.There is substantial inter-, and modest intra-, observer variability among head and neck pathologists for ECE in p16+ OPSCC, which is modestly improved by a defined system.

SUBMITTER: Lewis JS

PROVIDER: S-EPMC4875754 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Inter- and intra-observer variability in the classification of extracapsular extension in p16 positive oropharyngeal squamous cell carcinoma nodal metastases.

Lewis James S JS Tarabishy Yaman Y Luo Jingqin J Mani Haresh H Bishop Justin A JA Leon Marino E ME Prasad Manju L ML Xu Haodong H Di Palma Silvana S

Oral oncology 20150817 11

<h4>Objective</h4>Discern inter- and intra-observer variability in the classification of extracapsular extension (ECE) in p16+ oropharyngeal (OP) SCC comparing pathologists' own criteria versus those of a well-defined classification system.<h4>Methods</h4>Five pathologists reviewed 50 digitally scanned nodal metastasis slides in three Rounds. Round One was by their own criteria as ECE present or absent, and Rounds Two and Three were with a defined ECE system: Grade 0 (no ECE), 0c (no ECE - thick ...[more]

PMID: 26293844

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Project description:INTRODUCTION:Extracapsular extension (ECE) in regional lymph nodes and positive surgical margins (PSM) are considered high-risk adverse pathologic features in patients with oropharyngeal squamous cell carcinoma (OPSCC) that each constitute an indication for postoperative adjuvant chemoradiation. We identify pre-operative clinical factors that can predict post-operative ECE and/or PSM and create a nomogram to help clinical decision making. METHODS:Adult patients with non-metastatic OPSCC with initial surgical treatment and confirmed HPV status diagnosed between 2010 and 2014 were selected from the National Cancer Database. Clinical staging was modified to American Joint Committee on Cancer 8th edition parameters. Logistic regression was used for multivariate analysis to identify predictors of pathologic ECE and/or PSM. RESULTS:5065 patients were included. 47.5% of the 3336 HPV-positive (HPV+) patients had ECE/PSM. 40.4% of the 1729 HPV-negative (HPV-) patients with had ECE/PSM. A model was built that included age, clinical ECE, tumor grade, and clinical T and N staging for HPV+ patients. Increasing N-classification was highly predictive of pathologic ECE and/or PSM (N1 OR?=?3.6, N2 OR?=?7.0, N3 OR?=?11.2, p?<?0.01). Clinical ECE (OR?=?4.1, p?<?0.01), tumor grade (ORs 2.2-4.4 with p?<?0.05), and increasing clinical T-classification (ORs 1.2-1.8, p?<?0.05) were also associated with ECE and/or PSM. A similar model was built for HPV- with similar predictive capability. Two internally validated nomograms were designed that demonstrated good discrimination (HPV+ AUC?=?0.66, 95% CI: 0.64-0.68, and HPV- AUC?=?0.70, 95% CI: 0.67-0.72) and good calibration (goodness-of-fit statistic of HPV+ 6.32, p?=?0.61 and HPV- 11.66, p?=?0.17). CONCLUSIONS:These are the first nomograms designed to help predict ECE or PSM for both HPV+ and HPV- OPSCC. The nomograms can facilitate shared decision-making between clinicians and patients as they consider upfront treatment selection for OPSCC.

Project description:Importance:Clinical trials that deintensify treatment for patients with suspected human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) use p16 expression to identify HPV-mediated tumors and guide treatment. While p16 staining has a strong correlation with good outcomes, approximately 12% of p16-positive patients have recurrent disease. Biomarkers that reveal tumor-specific characteristics, such as nodal involvement, may change therapy decisions. Objective:To assess whether if a tumor-specific genetic signature exists for node-negative vs node-positive HPV 16-positive/p16-positive OPSCCs. Design, Setting, and Participants:This was a retrospective cohort study with randomized case selection for p16 OPSCCs undertaken at a university-based, tertiary care cancer center. Samples were collected from patients with p16-positive OPSCC. A total of 21 HPV 16/p16-positive tumors were used in this study. Main Outcomes and Measures:Gene expression profiles of node-negative vs node-positive tumor samples were evaluated using a differential expression analysis approach and the sensitivity and specificity of a molecular signature was determined. Results:Among the 21 patients in the study (3 women, 18 men; mean [SD] age, 54.6 [9.6] years), 6 had node-negative disease and 15 had node-positive disease. Using differential expression analysis, we found 146 genes that were significantly different in patients with node-negative disease vs those with node-positive disease, of which 15 genes were used to create a genetic signature that could distinguish node-negative-like from node-positive-like disease. The resultant molecular signature has a sensitivity of 88.2% (95% CI, 63.6%-98.5%) and specificity of 85.7% (95% CI, 42.1%-99.6%). The positive likelihood ratio of this signature was 6.1 (95% CI, 1.0-38.2) and the negative likelihood ratio was 0.1 (95% CI, 0.04-0.5). Given this population's prevalence of node-positive disease of 70.8%, the positive- and negative-predicative values for this gene signature were 93.7% (95% CI, 70.8%-98.9%) and 75.0% (95% CI, 44.1%-92.0%), respectively. In addition, we developed a gene signature using agnostic, machine learning software that identified a 40-gene profile that predicts node-negative disease from node-positive disease (area under the curve, 0.93; 95% CI, 0.63-1.00). Conclusions and Relevance:Many HPV-16 and p16-positive tumors are treated as "lower-risk," but they do not have similar genetic compositions at the biological level. The identification of subgroups with unique expression patterns, such as those with nodal metastases, may guide physicians toward alternative or more aggressive therapies. In our study, unguided clustering suggested that that the larger biological characteristics of a tumor could be a better prognostic biomarker.

Project description:BackgroundMusculoskeletal disorders particularly in the back and lower extremities are common among marines. Here, movement-control tests are considered clinically useful for screening and follow-up evaluation. However, few studies have addressed the reliability of clinical tests, and no such published data exists for marines. The present aim was therefore to determine the inter- and intra-observer reliability of clinically convenient tests emphasizing movement control of the back and hip among marines. A secondary aim was to investigate the sensitivity and specificity of these clinical tests for discriminating musculoskeletal pain disorders in this group of military personnel.MethodsThis inter- and intra-observer reliability study used a test-retest approach with six standardized clinical tests focusing on movement control for back and hip. Thirty-three marines (age 28.7 yrs, SD 5.9) on active duty volunteered and were recruited. They followed an in-vivo observation test procedure that covered both low- and high-load (threshold) tasks relevant for marines on operational duty. Two independent observers simultaneously rated performance as "correct" or "incorrect" following a standardized assessment protocol. Re-testing followed 7-10 days thereafter. Reliability was analysed using kappa (κ) coefficients, while discriminative power of the best-fitting tests for back- and lower-extremity pain was assessed using a multiple-variable regression model.ResultsInter-observer reliability for the six tests was moderate to almost perfect with κ-coefficients ranging between 0.56-0.95. Three tests reached almost perfect inter-observer reliability with mean κ-coefficients > 0.81. However, intra-observer reliability was fair-to-moderate with mean κ-coefficients between 0.22-0.58. Three tests achieved moderate intra-observer reliability with κ-coefficients > 0.41. Combinations of one low- and one high-threshold test best discriminated prior back pain, but results were inconsistent for lower-extremity pain.ConclusionsOur results suggest that clinical tests of movement control of back and hip are reliable for use in screening protocols using several observers with marines. However, test-retest reproducibility was less accurate, which should be considered in follow-up evaluations. The results also indicate that combinations of low- and high-threshold tests have discriminative validity for prior back pain, but were inconclusive for lower-extremity pain.

Project description:The aim of the present study is to evaluate the intra- and inter-observer agreement in assessing the renal function by means of 99mTc-MAG3 diuretic renography. One hundred and twenty adults were enrolled in the study. One experienced and one junior radiographer processed the renograms twice by assigning manual and semi-automated regions of interest. The differential renal function (DRF, %), time to maximum counts for the right and left kidney (TmaxR-TmaxL, min) and time to half-peak counts (T1/2, min) were calculated. The Bland-Altman analysis (bias±95% limits of agreement), Lin's concordance correlation coefficient and weighted Fleiss' kappa coefficient were used to assess agreement. Based on the Bland-Altman analysis, the intra-observer repeatability results for the experienced radiographer using the manual and the semi-automated techniques were 0.2 ± 2.6% and 0.3 ± 6.4% (DRF), respectively, -0.01 ± 0.24 and 0.00 ± 0.34 (TmaxR), respectively, and 0.00 ± 0.26 and 0.00 ± 0.33 (TmaxL), respectively. For the junior radiographer, the respective results were 0.5 ± 5.0% and 0.8 ± 9.4% (DRF), 0.00 ± 0.44 and 0.01 ± 0.28 (TmaxR), and 0.01 ± 0.28 and -0.02 ± 0.44 (TmaxL). The inter-observer repeatability for the manual method was 0.6 ± 5.0% (DRF), -0.10 ± 0.42 (TmaxR) and -0.05 ± 0.38 (TmaxL), and for the semi-automated method -0.2 ± 9.1% (DRF), 0.00 ± 0.31 (TmaxR) and -0.05 ± 0.40 (TmaxL). The weighted Fleiss' kappa coefficient for the T1/2 assessments ranged between 0.85-0.97 for both intra- and inter-observer repeatability with both methods. These findings suggest a very good repeatability in DRF assessment with the manual method-especially for the experienced observer-but a less good repeatability with the semi-automated approach. The calculation of Tmax was also operator-dependent. We conclude that reader experience is important in the calculation of renal parameters. We therefore encourage reader training in renal scintigraphy. Moreover, the manual tool seems to perform better than the semi-automated tool. Thus, we encourage cautious use of automated tools and adjunct validation by manual methods where possible.

Dataset Information

Inter- and intra-observer variability in the classification of extracapsular extension in p16 positive oropharyngeal squamous cell carcinoma nodal metastases.

Publications

Inter- and intra-observer variability in the classification of extracapsular extension in p16 positive oropharyngeal squamous cell carcinoma nodal metastases.

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