Using guideline-based clinical decision support in oncological multidisciplinary team meetings: A prospective, multicenter concordance study.

BACKGROUND: Multidisciplinary team meetings formulate guideline-based individual treatment plans based on patient and disease characteristics and motivate reasons for deviation. Clinical decision trees could support multidisciplinary teams to adhere more accurately to guidelines. Every clinical decision tree is tailored to a specific decision moment in a care pathway and is composed of patient and disease characteristics leading to a guideline recommendation. OBJECTIVE: This study investigated (1) the concordance between multidisciplinary team and clinical decision tree recommendations and (2) the completeness of patient and disease characteristics available during multidisciplinary team meetings to apply clinical decision trees such that it results in a guideline recommendation. METHODS: This prospective, multicenter, observational concordance study evaluated 17 selected clinical decision trees, based on the prevailing Dutch guidelines for breast, colorectal and prostate cancers. In cases with sufficient data, concordance between multidisciplinary team and clinical decision tree recommendations was classified as concordant, conditional concordant (multidisciplinary team specified a prerequisite for the recommendation) and non-concordant. RESULTS: Fifty-nine multidisciplinary team meetings were attended in 8 different hospitals, and 355 cases were included. For 296 cases (83.4%), all patient data were available for providing an unconditional clinical decision tree recommendation. In 59 cases (16.6%), insufficient data were available resulting in provisional clinical decision tree recommendations. From the 296 successfully generated clinical decision tree recommendations, the multidisciplinary team recommendations were concordant in 249 (84.1%) cases, conditional concordant in 24 (8.1%) cases and non-concordant in 23 (7.8%) cases of which in 7 (2.4%) cases the reason for deviation from the clinical decision tree generated guideline recommendation was not motivated. CONCLUSION: The observed concordance of recommendations between multidisciplinary teams and clinical decision trees and data completeness during multidisciplinary team meetings in this study indicate a potential role for implementation of clinical decision trees to support multidisciplinary team decision-making.

Extracapsular extension in the positive sentinel lymph node: a marker of poor prognosis in cT1-2N0 breast cancer patients?

OBJECTIVE: This study aims to evaluate whether extracapsular extension (ECE) in the sentinel lymph node (SLN) is associated with involvement of ≥ 4 lymph node metastases at completion axillary lymph node dissection (ALND) and the effect on 5-year disease-free survival (DFS) and 10-year overall survival (OS). ECE in a SLN is usually a contraindication for omitting completion ALND in cT1-2N0 breast cancer patients treated with breast-conserving therapy and 1-2 positive SLN(s). METHODS: All cT1-2N0 breast cancer patients with 1-3 positive SLN(s) who underwent ALND between 2005 and 2008 were selected from the Netherlands Cancer Registry. Logistic regression analysis was used to determine the association between ECE and ≥ 4 lymph node metastases. Five-year DFS and 10-year OS were analyzed using Kaplan-Meier survival analysis. Cox regression analysis was performed to correct for other prognostic factors. RESULTS: A total of 3502 patients were included. Information on ECE was available for 2111 (60.3%) patients, consisting of 741 (35.1%) patients with and 1370 (64.9%) without ECE. The incidence of ≥ 4 lymph node metastases was 116 (15.7%) in the ECE group vs. 80 (5.8%) in the group without ECE (p < 0.001). Five-year DFS rate was 86.4% in the ECE group compared to 88.8% in the group without ECE (p = 0.085). 10-year OS rate was 78.6% compared to 83.0% (p = 0.018), respectively. Cox regression analysis showed that ECE was not an independent prognostic factor for both DFS and OS. CONCLUSIONS: ECE was significantly associated with involvement of ≥ 4 lymph node metastases in the completion ALND group. ECE was not an independent prognostic factor for both DFS and OS.

Neo-adjuvant chemotherapy followed by surgery versus surgery alone in high-risk patients with resectable colorectal liver metastases: the CHARISMA randomized multicenter clinical trial.

BACKGROUND: Efforts to improve the outcome of liver surgery by combining curative resection with chemotherapy have failed to demonstrate definite overall survival benefit. This may partly be due to the fact that these studies often involve strict inclusion criteria. Consequently, patients with a high risk profile as characterized by Fong's Clinical Risk Score (CRS) are often underrepresented in these studies. Conceptually, this group of patients might benefit the most from chemotherapy. The present study evaluates the impact of neo-adjuvant chemotherapy in high-risk patients with primary resectable colorectal liver metastases, without extrahepatic disease. Our hypothesis is that adding neo-adjuvant chemotherapy to surgery will provide an improvement in overall survival (OS) in patients with a high-risk profile. METHODS/DESIGN: CHARISMA is a multicenter, randomized, phase III clinical trial. Patients will be randomized to either surgery alone (standard treatment, arm A) or to 6 cycles of neo-adjuvant oxaliplatin-based chemotherapy, followed by surgery (arm B). Patients must be ≥ 18 years of age with liver metastases of histologically confirmed primary colorectal carcinoma. Patients with extrahepatic metastases are excluded. Liver metastases must be deemed primarily resectable. Only patients with a CRS of 3-5 are eligible. The primary study endpoint is OS. Secondary endpoints are progression free survival (PFS), quality of life, morbidity of resection, treatment response on neo-adjuvant chemotherapy, and whether CEA levels can predict treatment response. DISCUSSION: CHARISMA is a multicenter, randomized, phase III clinical trial that will provide an answer to the question if adding neo-adjuvant chemotherapy to surgery will improve OS in a well-defined high-risk patient group with colorectal liver metastases. TRIAL REGISTRATION: The CHARISMA is registered at European Union Clinical Trials Register (EudraCT), number: 2013-004952-39 , and in the "Netherlands national Trial Register (NTR), number: 4893.

Polymerase chain reaction for Enterococcus faecalis in drain fluid: the first screening test for symptomatic colorectal anastomotic leakage. The Appeal-study: analysis of parameters predictive for evident anastomotic leakage.

PURPOSE: With current diagnostic methods, the majority of patients with symptomatic colorectal anastomotic leakage(CAL) is identified approximately 1 week after operation.The aim of this study is to determine whether real-time polymerase chain reaction (RT-PCR) for detection of Escherichia coli and Enterococcus faecalis on drain fluid can serve as a screening test for CAL in the early postoperative phase. METHODS: All patients included in this multicenter prospective observational study underwent left-sided colorectal resection for both malignant and benign diseases with construction of an anastomosis. In all patients, an intra-abdominal drain was placed during operation. During the first five postoperative days, drain fluid was processed for RT-PCR. The quantitative results of the RT-PCR on days 2 to 5 were compared to the results of day 1 in order to detect concentration changes. RESULTS: In total, 243 patients, with both benign and malignant diseases, were included of whom 19 (7.8 %) developed symptomatic CAL. An increase in E. coli concentration was found insignificantly more patients with CAL on day 4 and 5 [p =0.0004; diagnostic odds ratio (DOR) 7.9]. For E. faecalis, this result was found for days 2, 3, and 4 (p <0.003) with highest DOR on day 3 (31.6). Sensitivity and negative predictive values were 92.9 and 98.7 %, respectively, virtually ruling out CAL in case of negative test results on the third postoperative day. CONCLUSION: Quantitative PCR for E. faecalis performed on drain fluid may be an objective, affordable and fast screening tool for symptomatic colorectal anastomotic leakage.

High level of distress in long-term survivors of thyroid carcinoma: results of rapid screening using the distress thermometer.

CONTEXT: Cancer patients are at increased risk for distress. The Distress Thermometer (DT) and problem list (PL) are short-tools validated and recommended for distress screening in cancer patients. OBJECTIVE: To investigate the level of distress and problems experienced by survivors of differentiated non-medullary thyroid carcinoma (DTC), using the DT and PL and whether this correlates with clinical and demographical variables. PARTICIPANTS, DESIGN AND SETTING: All 205 DTC patients, under follow-up at the outpatient clinic of our university hospital, were asked to fill in the DT and PL, hospital anxiety and depression scale (HADS), illness cognition questionnaire (ICQ) and an ad hoc questionnaire. Receiver Operator Characteristic analysis (ROC) was used to establish the optimal DT cut-off score according to HADS. Correlations of questionnaires scores with data on diagnosis, treatment and follow-up collected from medical records were analyzed. RESULTS: Of the 159 respondents, 145 agreed to participate [118 in remission, median follow-up 7.2 years (range 3 months-41 years)]. Of these, 34.3% rated their distress score ≥5, indicating clinically relevant distress according to ROC analysis. Patients reported physical (86%) over emotional problems (76%) as sources of distress. DT scores correlated with HADS scores and ICQ subscales. No significant correlations were found between DT scores and clinical or demographical characteristics except for employment status. CONCLUSION: Prevalence of distress is high among patients with DTC even after long-term remission and cannot be predicted by clinical and demographical characteristics. DT and PL are useful screening instruments for distress in DTC patients and could easily be incorporated into daily practice.

Gender differences in tumor characteristics, treatment and survival of colorectal cancer: A population-based study.

BACKGROUND: The importance of sex and gender as modifiers of health and disease is increasingly recognized. The aim of this study was to analyze gender differences in incidence, tumor characteristics, treatment and relative survival (RS) in colorectal cancer (CRC). METHODS: Observational population-based study including patients diagnosed with CRC in the Netherlands between 2010 and 2020. Stratified by localization (colon/rectum) and age (18-55/56-70/≥71years), gender differences in incidence, tumor characteristics, treatment and RS were analyzed. Multivariable regression was used to analyze the influence of gender on treatment and RS. RESULTS: The age-standardized incidence per 100,000 person-years of colon and rectal cancer is higher among men than women (colon: 41.2 versus 32.4, rectum: 22.8 versus 12.6). Besides differences in patient- and tumor characteristics, differences in treatment allocation and RS were observed. Most strikingly, women aged ≥ 71 years with stage IV colon cancer are less often treated with systemic therapy (31.3 % versus 28.4 %, adjusted odds ratio (OR) 0.63, 95 % CI 0.48-0.83) and more often receive best supportive care only (47.6 % versus 40.0 %, adjusted OR 1.58, 95 % CI 1.19-2.11). CONCLUSION: Statistically significant and clinically relevant gender differences in incidence, patient- and tumor characteristics and treatment allocation are observed in patients with CRC. Reasons for differences in treatment allocation deserve further investigation.

Brief fixation enables same-day breast cancer diagnosis with reliable assessment of hormone receptors, E-cadherin and HER2/Neu.

AIMS: Preoperative core needle biopsy (CNB) is commonly used to confirm the diagnosis of breast cancer. For treatment purposes and for determining histological type, especially in case of neoadjuvant therapy, oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status and E-cadherin assessments are crucial. Considering the increasing demand for same-day diagnosis of breast lesions, an accelerated method of CNB processing was developed, in which the tissue fixation time is radically reduced. METHODS: To determine whether short fixation time frustrates assessment of ER, PR and E-cadherin immunohistochemistry (IHC) and HER2 fluorescence in situ hybridisation (FISH), 69 consecutive patients with 70 invasive breast carcinomas were included through the same-day diagnostics programme of breast lesions of the Radboud university medical center and the hospital Pantein. IHC for ER, PR and E-cadherin and HER2 FISH were compared between CNBs fixed for approximately 60-90 min and traditionally fixed resection specimens. RESULTS: Overall agreement between CNBs and resection specimens was 98.6% for ER (p<0.001; κ=0.93), 90.0% for PR (p<0.001; κ=0.75), 100% for E-cadherin (p<0001; κ=1.00) and 98.6% (p<0.001; κ=0.94) for HER2 FISH. Positive and negative predictive values were respectively 98.4% and 100% for ER, 95.9% and 76.2% for PR, 100% and 100% for E-cadherin and 90% and 100% for HER2 FISH. CONCLUSIONS: Hormone receptors and E-cadherin IHC and HER2 FISH are highly comparable between briefly fixed CNBs and the corresponding traditionally fixed resection specimens, and can therefore reliably be used in the daily clinical practice of same-day diagnostics of breast cancer.

Acute phase proteins in drain fluid: a new screening tool for colorectal anastomotic leakage? The APPEAL study: analysis of parameters predictive for evident anastomotic leakage.

BACKGROUND: We aim to determine if C-reactive protein (CRP), lipopolysaccharide-binding protein (LBP), and procalcitonin (PCT) in drain fluid can serve as screening tools for colorectal anastomotic leakage (CAL). METHODS: Patients included in this multicenter prospective observational study underwent left hemicolectomy, sigmoid resection, high anterior resection, low anterior resection, or subtotal colectomy. During the first 5 postoperative days, CRP, LBP, and PCT were determined on drain fluid. RESULTS: In total 243 patients were included, of whom 19 (8%) developed CAL. CRP levels were higher in patients with leakage on day 3 and day 5, levels of LBP were higher on days 2, 3, and 4, and PCT levels were higher on day 5. Multivariate analysis showed LBP to be significantly related to CAL. An increase in the average initial value at the first postoperative day with 1 standard deviation increased the risk of leakage by 1.6 times. CONCLUSION: Increased concentrations of LBP in drain fluid are significantly associated to a higher chance of CAL and could contribute in a future prognostic model for CAL.