Malnutrition prevalence in cancer patients in Belgium: The ONCOCARE study.

RATIONALE: Unintentional weight loss and malnutrition are common among cancer patients. Malnutrition has been associated with impaired health-related quality of life, less well-tolerated chemotherapy regimens and shorter life duration. In Belgium there is a lack of epidemiological data on malnutrition in oncology patients at advanced stages of the disease. METHODS: Malnutrition assessment data was collected through a prospective, observational study in 328 patients who started a neoadjuvant anticancer therapy regimen or who started 1st, 2nd or 3rd line anticancer therapy for a metastatic cancer via 3 visits according to regular clinical practice (baseline visit (BV) maximum 4 weeks before start therapy, 1st Follow up visit (FUV1) ± 6 weeks after start therapy, FUV2 ± 4 months after start therapy). Malnutrition screening was evaluated using the Nutritional Risk Screening score 2002 (NRS-2002)and the diagnosis of malnutrition by the GLIM criteria. In addition, SARC-F questionnaire and Fearon criteria were used respectively to screen for sarcopenia and cachexia. RESULTS: Prevalence of malnutrition risk at BV was high: 54.5% of the patients had a NRS ≥ 3 (NRS 2002) and increased during the study period (FUV1: 73.2%, FUV2: 70.1%). Prevalence of malnutrition based on physician subjective assessment (PSA) remained stable over the study period but was much lower compared to NRS results (14.0%-16.5%). At BV, only 10% of the patients got a nutrition plan and 43.9% received ≤ 70% of nutritional needs, percentage increased during FU period (FUV1: 68.4%, FUV2: 67.6%). Prevalence of sarcopenia and cachexia were respectively 12.4% and 38.1% at BV and without significant variation during the study period, but higher than assessed by PSA (11.6% and 6.7% respectively). Figures were also higher compared to PSA. There were modifications in cancer treatment at FUV1 (25.2%) and at FUV2 (50.8%). The main reasons for these modifications at FUV1 were adverse events and tolerability. Patient reported daily questionnaires of food intake showed early nutritional deficits, preceding clinical signs of malnutrition, and therefore can be very useful in the ambulatory setting. CONCLUSIONS: Prevalence of malnutrition and cachexia was high in advanced cancer patients and underestimated by physician assessment. Earlier and rigorous detection of nutritional deficit and adjusted nutritional intake could lead to improved clinical outcomes in cancer patients. Reporting of daily caloric intake by patients was also very helpful with regards to nutritional assessment.

Severe treatment-induced inflammatory polyarthritis in advanced melanoma patients: 2 case reports.

Immune checkpoint inhibitors (ICI) and targeted therapies form the therapeutic mainstay for v-Raf murine sarcoma viral oncogene homolog B V600-mutated metastatic melanoma. Both treatment regimens can cause inflammatory arthritis. The reported incidence of treatment-induced inflammatory arthritis is low, though presumably underestimated due to lack of awareness, clear definitions and uniform grading systems. Nevertheless, recognition is important as inflammatory arthritis can become chronic and thus affect the quality of life beyond treatment. In this short communication, we present two patients with metastatic melanoma treated with ICI and targeted therapies who develop severe polyarthritis. Based on their clinical discourse we describe standard inflammatory arthritis treatment modalities and more advanced immunomodulatory treatment options with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biologic DMARDs (bDMARDs). Long-term immunosuppressive treatment with glucocorticoids or DMARDs in this setting raises concerns about antitumour response and potential carcinogenic risk. Current literature on this topic is scarce, heterogeneous and retrospective. Prospective analysis of cancer patients treated with DMARDs is needed to clearly address these concerns.

Which Factors Predict Overall Survival in Patients With Metastatic Castration-Resistant Prostate Cancer Treated With Abiraterone Acetate Post-Docetaxel?

BACKGROUND: Abiraterone acetate (AA) increases overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel. However, survival time varies substantially between individuals. Our goal was to identify prognostic factors that better estimate OS. MATERIALS AND METHODS: This is a retrospective multicentric analysis of 368 patients with mCRPC starting AA with prednisone after docetaxel. Cox proportional hazards statistics were applied. A multivariate model was constructed based on significant univariate predictors by using a manual stepwise forward and backward selection strategy. Model performance was determined by using receiver operating characteristic (ROC) curves. RESULTS: Univariate analysis identified 20 significant OS predictors. A multivariate model was constructed, based on 220 patients, incorporating 5 independent risk factors for decreased OS at the time of AA initiation: hemoglobin < 12 g/dL (hazard ratio [HR] 2.02), > 10 metastases (HR 1.80), ECOG performance status ≥ 2 (HR 1.88), radiographic progression (HR 1.50), and time since diagnosis < 90 months (HR 1.66, all P < .05). Patients were stratified into 3 groups: good (0-2 risk factors, median OS 22.6 months), intermediate (3 risk factors, median OS 13.9 months), and poor prognosis (4-5 risk factors, median OS 6.2 months). The area under the ROC curve based on the event "death by the time of median OS (13.3 months)" was 0.736 (95% confidence interval 0.670-0.803). CONCLUSION: We identified 5 readily available risk factors independently associated with decreased OS. The resulting model may be used for patient counseling in daily clinical practice, as well as patient stratification in clinical trials.

Abiraterone acetate post-docetaxel for metastatic castration-resistant prostate cancer in the Belgian compassionate use program.

BACKGROUND: Abiraterone acetate (AA) is licensed for treating metastatic castration-resistant prostate cancer (mCRPC). Real-world data on oncological outcome after AA are scarce. The current study assesses efficacy and safety of AA in mCRPC patients previously treated with docetaxel who started treatment during the Belgian compassionate use program (January 2011-July 2012). PATIENTS AND METHODS: Records from 368 patients with mCRPC from 23 different Belgian hospitals who started AA 1000mg per day with 10mg prednisone or equivalent were retrospectively reviewed (September 2013-December 2014). Prostate-specific antigen (PSA) response (decrease≥50%), time to PSA progression (increase>50% over PSA nadir in case of PSA response/>25% in absence of PSA response), time to radiographic progression (on bone scans or for soft tissue lesions using Response Evaluation Criteria In Solid Tumors 1.1), overall survival and adverse event rate (Common Terminology Criteria for Adverse Events v4.03) were analyzed. Kaplan-Meier statistics were applied. RESULTS: Overall, 92 patients (25%) had an Eastern Cooperative Oncology Group performance status≥2. Median age was 73 years, median PSA was 103ng/dl. PSA response was observed in 131 patients (37.4%). Median time to PSA and radiographic progression was 4.1 months (95% CI: 3.6-4.6) and 5.8 months (5.3-6.4), respectively. Median overall survival was 15.1 months (13.6-16.6). Most common grade 3 to 4 adverse events were anemia (13.9%), hypokalemia (7.3%), fatigue (6.8%), and pain (6.3%). Median duration of AA treatment was 5.3 months (interquartile range: 2.8-10.3). The main study limitation is its retrospective design. CONCLUSIONS: These real-world data on post-docetaxel AA efficacy are in line with the COU-AA-301 trial. Importantly, incidence of severe anemia and hypokalemia is up to 50% higher than reported in previous studies.

Promoting evidence-based management of anemia in cancer patients: concurrent and discriminant validity of RESPOND, a web-based clinical guidance system based on the EORTC guidelines for supportive care in cancer.

GOAL OF WORK: The goal of this study is to test the validity of RESPOND, a web-based decision support system to assess and manage anemia in cancer patients as per the European Organisation for Research and Treatment of Cancer (EORTC) guidelines. The intraclass correlation metrics for the algorithmic definitions were reported previously. Reported here are the concurrent validity, the extent to which clinicians' anemia management is guidelines-congruent when using the system; and discriminant validity, the extent to which clinicians practice in congruence with guidelines when vs. when not using the system. PATIENTS AND METHODS: Hybrid matched design with precohort (retrospective; clinicians not using RESPOND) and postcohort (prospective; clinicians using RESPOND) of anemic patients matched on cancer type and chemotherapy regimen and followed up over 4 months after treatment initiation with erythropoietic proteins (34 patients per cohort; total N = 68). Congruence scores quantified the extent to which anemia management was congruent with the EORTC guidelines (range 0-10). MAIN RESULTS: Hemoglobin (Hb) increased significantly for both cohorts, but the postcohort group showed more rapid rate of Hb increase over time (p < 0.006), higher Hb by visit 4 (p = 0.007), and greater Hb increase by visit 4 (p = 0.006). Concurrent validity was high with mean postcohort congruence scores of 8.18 +/- 1.38. Discriminant validity was inferred from statistically significant differences in mean congruence scores between cohorts (p < 0.001) and from the postcohort having odds ratios of 3.64 for patients to reach Hb >or= 11 g/dL and 2.91 to achieve Hb >or= 12 g/dL. CONCLUSIONS: RESPOND, a validated computerized clinical guidance system with an incremental effect beyond the pharmacotherapeutic effect of erythropoietic proteins, offers clinicians accurate and safe guidance in managing anemia in cancer patients.

Managing cancer-related anaemia in congruence with the EORTC guidelines is an independent predictor of haemoglobin outcome: initial evidence from the RESPOND study.

PURPOSE: To model the relationship between scores for practicing in congruence (CSs; 0-10) with EORTC guidelines for erythropoietic proteins (EPs) and haemoglobin (Hb) outcomes observed in the validation study of the RESPOND system. METHODS: Thirty four patient pairs matched on cancer type and chemotherapy in pre- (retrospective; clinicians not using RESPOND) and post-cohorts (prospective; clinicians using RESPOND) followed over 4 months following EP treatment initiation. CSs quantify the extent that care was guideline-adherent. Linear and logistic regressions controlling for cohort examined Hb outcomes as a function of CSs. RESULTS: A one-point increase in CS was associated with 0.60g/dL increase in Hb at month 4 (R(2)=0.40) and 0.56g/dL increase in Hb change from month 1-4 (R(2)=0.33). Each one-point increase in CS increased the odds of reaching Hb>or=11g/dL by 3.14 (R(2)=0.42) and Hb>or=12g/dL by 2.77 (R(2)=0.45). CONCLUSION: Guideline-adherent EP treatment may improve Hb outcomes but specifically designed outcomes studies are necessary.

Promoting evidence-based management of anemia in cancer patients: background, development, and scientific validation of RESPOND, a web-based clinical guidance system based on the EORTC guidelines.

The 2006 EORTC guidelines for erythropoietic proteins in cancer-related anemia provide the most up-to-date assessment of the evidence base. Considering general concerns in medicine about clinicians' adoption of evidence-based guidelines, it is critical to find ways of bringing guidelines to the point of care. We describe the rationale behind RESPOND, a web-based clinical guidance system based on the EORTC guidelines, and the methodologies of two studies conducted to validate the system. In a first descriptive study, experts are asked to rate the accuracy of every algorithm derived from the guidelines. In a second step and using a hybrid matched pre-post design, separate retrospective and prospective patient cohorts matched by type of cancer and similarity of chemotherapy regimen (33 pairs) are used to examine the extent to which clinicians' practice patterns converge with the EORTC guidelines when they use or not use the RESPOND system. It is hypothesized that these studies will provide the necessary validation for RESPOND as an evidence-based clinical support tool.

Intraclass correlation metrics for the accuracy of algorithmic definitions in a computerized decision support system for supportive cancer care.

As part of the development of a computerized clinical decision support system for anemia management in cancer patients, we applied psychometric principles and techniques to assess the accuracy of the algorithmic operationalizations of a set of evidence-based practice guidelines. In an iterative rating process, five medical and nursing experts rated 27 algorithmic sets derived from 18 guidelines, the objective being an intraclass coefficient (ICC) exceeding 0.90. The first round of review yielded an ICC of 1.00 for 22 sets. After revision and resubmission to the expert panel, an ICC of 1.00 was obtained for the additional five sets. The evolving decision support system is based on algorithms that accurately specify evidence-based guidelines for anemia management in cancer patients.