Relevance of shrinkage versus fragmented response patterns in rectal cancer

AIMS: Partial response to neoadjuvant chemoradiotherapy (CRT) presents with one of two main response patterns: shrinkage or fragmentation. This study investigated the relevance of these response patterns in rectal cancer, correlation with other response indicators, and outcome.METHODS AND RESULTS: The study included a test (n = 197) and a validation cohort (n = 218) of post-CRT patients with rectal adenocarcinoma not otherwise specified and a partial response. Response patterns were scored by two independent observers using a previously developed three-step flowchart. Tumour regression grading (TRG) was established according to both the College of American Pathologists (CAP) and Dworak classifications. In both cohorts, the predominant response pattern was fragmentation (70% and 74%), and the scoring interobserver agreement was excellent (k = 0.85). Patients with a fragmented pattern presented with significantly higher pathological stage (ypTNM II-IV, 78% versus 35%; P &lt; 0.001), less tumour regression with Dworak (P = 0.004), and CAP TRG (P = 0.005) compared to patients with a shrinkage pattern. As a predictor of prognosis, the shrinkage pattern outperformed the TRG classification and stratified patients better in overall (fragmented pattern, hazard ratio [HR] 2.04, 95% confidence interval [CI] 1.19-3.50, P = 0.008) and disease-free survival (DFS; fragmented pattern, HR 2.50, 95% CI 1.23-5.10, P = 0.011) in the combined cohorts. The multivariable regression analyses revealed pathological stage as the only independent predictor of DFS.CONCLUSIONS: The heterogeneous nature of tumour response following CRT is reflected in fragmentation and shrinkage. In rectal cancer there is a predominance of the fragmented pattern, which is associated with advanced stage and less tumour regression. While not independently associated with survival, these reproducible patterns give insights into the biology of tumour response.</p

Relevance of shrinkage versus fragmented response patterns in rectal cancer

AIMS: Partial response to neoadjuvant chemoradiotherapy (CRT) presents with one of two main response patterns: shrinkage or fragmentation. This study investigated the relevance of these response patterns in rectal cancer, correlation with other response indicators, and outcome.METHODS AND RESULTS: The study included a test (n = 197) and a validation cohort (n = 218) of post-CRT patients with rectal adenocarcinoma not otherwise specified and a partial response. Response patterns were scored by two independent observers using a previously developed three-step flowchart. Tumour regression grading (TRG) was established according to both the College of American Pathologists (CAP) and Dworak classifications. In both cohorts, the predominant response pattern was fragmentation (70% and 74%), and the scoring interobserver agreement was excellent (k = 0.85). Patients with a fragmented pattern presented with significantly higher pathological stage (ypTNM II-IV, 78% versus 35%; P &lt; 0.001), less tumour regression with Dworak (P = 0.004), and CAP TRG (P = 0.005) compared to patients with a shrinkage pattern. As a predictor of prognosis, the shrinkage pattern outperformed the TRG classification and stratified patients better in overall (fragmented pattern, hazard ratio [HR] 2.04, 95% confidence interval [CI] 1.19-3.50, P = 0.008) and disease-free survival (DFS; fragmented pattern, HR 2.50, 95% CI 1.23-5.10, P = 0.011) in the combined cohorts. The multivariable regression analyses revealed pathological stage as the only independent predictor of DFS.CONCLUSIONS: The heterogeneous nature of tumour response following CRT is reflected in fragmentation and shrinkage. In rectal cancer there is a predominance of the fragmented pattern, which is associated with advanced stage and less tumour regression. While not independently associated with survival, these reproducible patterns give insights into the biology of tumour response.</p

Relevance of shrinkage versus fragmented response patterns in rectal cancer

AIMS: Partial response to neoadjuvant chemoradiotherapy (CRT) presents with one of two main response patterns: shrinkage or fragmentation. This study investigated the relevance of these response patterns in rectal cancer, correlation with other response indicators, and outcome.METHODS AND RESULTS: The study included a test (n = 197) and a validation cohort (n = 218) of post-CRT patients with rectal adenocarcinoma not otherwise specified and a partial response. Response patterns were scored by two independent observers using a previously developed three-step flowchart. Tumour regression grading (TRG) was established according to both the College of American Pathologists (CAP) and Dworak classifications. In both cohorts, the predominant response pattern was fragmentation (70% and 74%), and the scoring interobserver agreement was excellent (k = 0.85). Patients with a fragmented pattern presented with significantly higher pathological stage (ypTNM II-IV, 78% versus 35%; P &lt; 0.001), less tumour regression with Dworak (P = 0.004), and CAP TRG (P = 0.005) compared to patients with a shrinkage pattern. As a predictor of prognosis, the shrinkage pattern outperformed the TRG classification and stratified patients better in overall (fragmented pattern, hazard ratio [HR] 2.04, 95% confidence interval [CI] 1.19-3.50, P = 0.008) and disease-free survival (DFS; fragmented pattern, HR 2.50, 95% CI 1.23-5.10, P = 0.011) in the combined cohorts. The multivariable regression analyses revealed pathological stage as the only independent predictor of DFS.CONCLUSIONS: The heterogeneous nature of tumour response following CRT is reflected in fragmentation and shrinkage. In rectal cancer there is a predominance of the fragmented pattern, which is associated with advanced stage and less tumour regression. While not independently associated with survival, these reproducible patterns give insights into the biology of tumour response.</p

Surgical Treatment of Renal Cell Cancer Liver Metastases: A Population-Based Study

Background: To evaluate outcomes of surgical treatment in patients with hepatic metastases from renal-cell carcinoma in the Netherlands, and to identify prognostic factors for survival after resection. Renal-cell carcinoma has an incidence of 2,000 new patients in the Netherlands each year (12.5/100,000 inhabitants). According to literature, half of these patients ultimately develop distant metastases with 20% involvement of the liver. Resection of renal-cell carcinoma liver metastases (RCCLM) is performed in only a minority of patients. Hence, little is known about outcome of resectable RCCLM. Methods: Patients were retrieved from local databases of theNetherlands Task Force for Liver Surgery (14 centers) and from the Dutch collective pathology database. Survival and prognostic factors were determined by Kaplan-Meier analysis and log rank test. Results: Thirty-three patients were identified who underwent resection (n = 29) or local ablation (n = 4) of RCCLM in the Netherlands between 1990 and 2008. These patients comprise 0.5% to 1% of the total population of patients diagnosed with RCCLM in that period. There was no operative mortality. The overall survival at 1, 3, and 5 years was 79, 47, and 43%, respectively. Metachronous metastases (n = 23, P = 0.03) and radical resection (n = 19, P < 0.001) were statistically significant prognosticators of ov

The development of instruments to measure the work disability assessment behaviour of insurance physicians

<p>Abstract</p> <p>Background</p> <p>Variation in assessments is a universal given, and work disability assessments by insurance physicians are no exception. Little is known about the considerations and views of insurance physicians that may partly explain such variation. On the basis of the Attitude - Social norm - self Efficacy (ASE) model, we have developed measurement instruments for assessment behaviour and its determinants.</p> <p>Methods</p> <p>Based on theory and interviews with insurance physicians the questionnaire included blocks of items concerning background variables, intentions, attitudes, social norms, self-efficacy, knowledge, barriers and behaviour of the insurance physicians in relation to work disability assessment issues. The responses of 231 insurance physicians were suitable for further analysis. Factor analysis and reliability analysis were used to form scale variables and homogeneity analysis was used to form dimension variables. Thus, we included 169 of the 177 original items.</p> <p>Results</p> <p>Factor analysis and reliability analysis yielded 29 scales with sufficient reliability. Homogeneity analysis yielded 19 dimensions. Scales and dimensions fitted with the concepts of the ASE model. We slightly modified the ASE model by dividing behaviour into two blocks: behaviour that reflects the assessment process and behaviour that reflects assessment behaviour.</p> <p>The picture that emerged from the descriptive results was of a group of physicians who were motivated in their job and positive about the Dutch social security system in general. However, only half of them had a positive opinion about the Dutch Work and Income (Capacity for Work) Act (WIA). They also reported serious barriers, the most common of which was work pressure. Finally, 73% of the insurance physicians described the majority of their cases as 'difficult'.</p> <p>Conclusions</p> <p>The scales and dimensions developed appear to be valid and offer a promising basis for future research. The results suggest that the underlying ASE model, in modified form, is suitable for describing the assessment behaviour of insurance physicians and the determinants of this behaviour. The next step in this line of research should be to validate the model using structural equation modelling. Finally, the predictive value should be tested in relation to outcome measurements of work disability assessments.</p

Recommendations for reporting tumor budding in colorectal cancer based on the International Tumor Budding Consensus Conference (ITBCC) 2016

Tumor budding is a well-established independent prognostic factor in colorectal cancer but a standardized method for its assessment has been lacking. The primary aim of the International Tumor Budding Consensus Conference (ITBCC) was to reach agreement on an international, evidence-based standardized scoring system for tumor budding in colorectal cancer. The ITBCC included nine sessions with presentations, a pre-meeting survey and an e-book covering the key publications on tumor budding in colorectal cancer. The ‘Grading of Recommendation Assessment, Development and Evaluation’ method was used to determine the strength of recommendations and quality of evidence. The following 10 statements achieved consensus: tumor budding is defined as a single tumor cell or a cell cluster consisting of four tumor cells or less (22/22, 100%). Tumor budding is an independent predictor of lymph node metastases in pT1 colorectal cancer (23/23, 100%). Tumor budding is an independent predictor of survival in stage II colorectal cancer (23/23, 100%). Tumor budding should be taken into account along with other clinicopathological features in a multidisciplinary setting (23/23, 100%). Tumor budding is counted on H&E (19/22, 86%). Intratumoral budding exists in colorectal cancer and has been shown to be related to lymph node metastasis (22/22, 100%). Tumor budding is assessed in one hotspot (in a field measuring 0.785 mm2) at the invasive front (22/22, 100%). A three-tier system should be used along with the budding count in order to facilitate risk stratification in colorectal cancer (23/23, 100%). Tumor budding and tumor grade are not the same (23/23, 100%). Tumor budding should be included in guidelines/protocols for colorectal cancer reporting (23/23, 100%). Members of the ITBCC were able to reach strong consensus on a single international, evidence-based method for tumor budding assessment and reporting. It is proposed that this method be incorporated into colorectal cancer guidelines/protocols and staging systems