Philippe Vergauwe

Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial

BACKGROUND Most patients who have active Crohns disease are treated initially with corticosteroids. Although this approach usually controls symptoms, many patients become resistant to or dependent on corticosteroids, and long exposure is associated with an increased risk of mortality. We aimed to compare the effectiveness of early use of combined immunosuppression with conventional management in patients with active Crohns disease who had not previously received glucocorticoids, antimetabolites, or infliximab. METHODS We did a 2-year open-label randomised trial at 18 centres in Belgium, Holland, and Germany between May, 2001, and January, 2004. We randomly assigned 133 patients to either early combined immunosuppression or conventional treatment. The 67 patients assigned to combined immunosuppression received three infusions of infliximab (5 mg/kg of bodyweight) at weeks 0, 2, and 6, with azathioprine. We gave additional treatment with infliximab and, if necessary, corticosteroids, to control disease activity. 66 patients assigned to conventional management received corticosteroids, followed, in sequence, by azathioprine and infliximab. The primary outcome measures were remission without corticosteroids and without bowel resection at weeks 26 and 52. Analysis was by modified intention to treat. This trial was registered with ClinicalTrials.gov, number NCT00554710. FINDINGS Four patients (two in each group) did not receive treatment as per protocol. At week 26, 39 (60.0%) of 65 patients in the combined immunosuppression group were in remission without corticosteroids and without surgical resection, compared with 23 (35.9%) of 64 controls, for an absolute difference of 24.1% (95% CI 7.3-40.8, p=0.0062). Corresponding rates at week 52 were 40/65 (61.5%) and 27/64 (42.2%) (absolute difference 19.3%, 95% CI 2.4-36.3, p=0.0278). 20 of the 65 patients (30.8%) in the early combined immunosuppression group had serious adverse events, compared with 19 of 64 (25.3%) controls (p=1.0). INTERPRETATION Combined immunosuppression was more effective than conventional management for induction of remission and reduction of corticosteroid use in patients who had been recently diagnosed with Crohns disease. Initiation of more intensive treatment early in the course of the disease could result in better outcomes.

Mucosal Healing Predicts Sustained Clinical Remission in Patients With Early-Stage Crohn's Disease

BACKGROUND & AIMS Few prospective data are available to support the clinical relevance of mucosal healing in patients with Crohns disease. This study examined whether complete healing, determined by endoscopy, predicts a better outcome in Crohns disease. METHODS One-hundred thirty-three newly diagnosed and treatment-naïve Crohns disease patients were given either a combination of immunosuppressive therapy (azathioprine) and 3 infusions of infliximab or treatment with conventional corticosteroids. Patients given azathioprine were given repeated doses of infliximab for relapses, patients given corticosteroids were given azathioprine in cases of corticosteroid dependency and infliximab only if azathioprine failed. A representative subset of 49 patients from the initially randomized cohort underwent ileocolonoscopy after 2 years of therapy. Correlation analysis was performed between different clinical parameters including endoscopic activity (Simple Endoscopic Score) and clinical outcome 2 years after this endoscopic examination. Data were available from 46 patients 3 and 4 years after therapy began. RESULTS Complete mucosal healing, defined as a simple endoscopic score of 0 after 2 years of therapy, was the only factor that predicted sustained, steroid-free remission 3 and 4 years after therapy was initiated; it was observed in 17 of 24 patients (70.8%) vs 6 of 22 patients with lesions detected by endoscopy (27.3%, Simple Endoscopic Score >0) (P = .036; odds ratio = 4.352; 95% confidence interval, 1.10-17.220). Fifteen of 17 patients with mucosal healing at year 2 maintained in remission without further infliximab infusions during years 3 and 4 (P = .032; odds ratio = 4.883; 95% confidence interval, 1.144-20.844). CONCLUSIONS Complete mucosal healing in patients with early-stage Crohns disease is associated with significantly higher steroid-free remission rates 4 years after therapy began.

Combination of gemcitabine and cetuximab in patients with advanced cholangiocarcinoma: a phase II study of the Belgian Group of Digestive Oncology

BACKGROUND Cholangiocarcinomas are uncommon tumours with a poor prognosis, that frequently present epidermal growth factor receptor overexpression. METHODS In a multi-centre phase II trial, patients with unresectable cholangiocarcinoma, naïve to chemotherapy, received Cetuximab (400 mg/m(2) at week 1, then 250 mg/m(2)/week) and Gemcitabine (1 g/m(2) on day 1, 8 and 15 every 4 weeks). Primary end point was progression-free survival (PFS) rate at 6 months, using a Simon 2-stage design. Moreover, we assessed the impact of KRAS status and skin toxic effect on efficacy. RESULTS Forty-four patients (41% locally advanced/59% metastatic) were enrolled. Median age was 61.5 years; ECOG PS was 0 (68%) or 1. Six months PFS reached 47%. Median OS was 13.5 months [95% confidence interval (CI) 9.8-31.8 months]. Nine patients (20.4%) had PR and disease-control rate was 79.5%. Grade 3/4-related toxic effects were haematological (52.2%), skin rash (13.6%) and fatigue (11.4%). KRAS mutations were found in 7 of 27 patients and had no influence on PFS. Skin toxic effect ≥grade 2 was associated with increased PFS (P = 0.05). CONCLUSION(S) Our study met its primary end point, suggesting that Gemcitabine-Cetuximab has activity in cholangiocarcinoma. KRAS status was not associated with PFS, unlike skin toxic effect, which could be used as a surrogate marker for efficacy. ClinicalTrials.gov Identifier: NCT00747097.

Validation of the Freund Clock Drawing Test as a screening tool to detect cognitive dysfunction in elderly cancer patients undergoing comprehensive geriatric assessment.

We aimed to validate the Freund Clock Drawing Test (CDT), with its predefined cutoff score of ≤4, as a screening tool to detect elderly cancer patients in need of a more in‐depth cognitive evaluation within a comprehensive geriatric assessment (CGA).

Predictors of baseline cancer-related cognitive impairment in cancer patients scheduled for a curative treatment.

Recent research in the field of cancer‐related cognitive impairments (CRCI) has shown CRCI presentation prior to treatment initiation. Some have attributed these problems to worry and fatigue, whereas others have suggested an influence of age, IQ, and other psychosocial and medical factors.

The use of uHear™ to screen for hearing loss in older patients with cancer as part of a comprehensive geriatric assessment

Abstract Objective: We previously validated uHear™ to screen for hearing loss in older patients with cancer without a known hearing loss, as part of a comprehensive geriatric assessment (CGA). In view of low specificity, we tested a new modified uHear™ scoring system as described by Handzel. Methods: Patients, aged ≥70 years, were evaluated by uHear™ and conventional audiometry, which is considered the gold standard, as part of a CGA. The pass or fail screening cut-off for uHear™ was defined as having ≥2 consecutive hearing grades starting from the moderate–severe threshold zone ranging from 0.5 to 2.0 kHz (modified Handzel-uHear™ scoring system). To accept the modified Handzel-uHear™ as screening tool, it was predefined that the combined sensitivity (S) and specificity (Sp) of the test (S + Sp/2) was at least 80% and that an actual combined (S + Sp)/2 of 90% would be found. Results: Ninety ears (45 subjects) were tested. Of those ears, 24.4% were identified as impaired by conventional audiometry. Modified Handzel-uHear™ identified 26.7% of tested ears as impaired. The combined (S + Sp)/2 of the modified Handzel-uHear™ was calculated as 77.5%, while in previous cohort, this was retrospectively calculated as 94.6%. A new uHear™ scoring system was proposed and tested in current and previous cohort. A (S + Sp)/2 of 80.2 and 78.8%, respectively, were obtained. Conclusion: uHear™ is a feasible tool for use within the CGA and shows promising results. However, further research is warranted to optimize the cut-off method before it could be routinely implemented within geriatric oncology.

924 Long-Term Outcomes of Top-Down Versus Step-up Treatment in Newly Diagnosed Crohn's Disease: Final Data

G A A b st ra ct s variables, healthcare utilization, comorbidities and baseline immunosuppressive medication use, to assess the relative effectiveness and safety of IFX and ADA. Results: Our cohort comprised 1869 biologic-naive UC pts (age, 42.3±16.0y; 50.8% males) who were prescribed IFX (n=1470) or ADA (n=399) as first-line anti-TNF agents, and followed over median of 1.7 years (IQR, 0.9-3.0). Baseline demographics, healthcare utilization (outpatient, inpatient or emergency room visits; imaging and endoscopic procedures), comorbidities and prior medication exposure was comparable between the two groups (Table 1). As compared to ADA, pts treated with IFX were significantly less likely to require IBD-related hospitalization and new steroid prescription, after adjusting for baseline demographic variables, healthcare utilization, comorbidities and baseline immunosuppressive medication use (Table 2). There was no significant difference in the risk of abdominal surgery, though the number of events was small. Persistence on therapy at 6 months was significantly higher for IFX (61.4%) compared to ADA (14.8%). The incidence of serious infections was comparable between IFXand ADA-treated pts (incidence rate per 100 patient years: IFX vs. ADA, 1.49 vs. 2.25). Conclusion: In a large cohort of biologic-naive UC pts, IFX appears superior to ADA as first-line anti-TNF agent for important clinically relevant outcomes, without increased risk of serious infections. This requires further validation in randomized trials. Baseline characteristics of biologic-naive patients with ulcerative colitis.

CPT-11 and mitomycin-C in heavily pre-treated patients with metastatic colorectal cancer: a belgian multicentre phase II study

3716 Background: Data on third-line chemotherapy for metastatic colorectal cancer are lacking and the treatment is questionable. The aim of this prospective study is to evaluate the safety and efficacy of CPT-11 combined with mitomycin-C in heavily pre-treated patients with metastatic colorectal cancer. This association might have synergistic activity. METHODS Fourty nine patients (median age: 61; range: 42-79); WHO PS 0/1/2: n = 16/29/4) were included. All patients had metastatic disease with progression after two lines of chemotherapy (Folfiri 1st line followed by Folfox 2d line, n = 33, Folfox 1st line followed by Folfiri 2d line, n = 13, other regimen, n = 3). The investigational regimen consisted of CPT-11 150 mg/m2 as a 90 min infusion D1 and mitomycin-C 5 mg/m2 as bolus D1, q 2 weeks. RESULTS All patients received at least one cycle of chemotherapy (median: 5.5; range: 1-15); dose reduction or delay occured in respectively 8 (16%) and 14 (28%) patients. Fourty six patients were evaluable for response: PR = 3/46 (6.5%); SD = 18/46 (39%); PD = 25/46 (54%). Median survival is not yet reached. Grade 3/4 toxicities occured in 18/49 patients (37%), hematological toxicities in 11/49 (22%), non hematological toxicities in 9/49 (18%). Febrile neutropenia occured in 2 patients with one toxic death. CONCLUSIONS CPT-11 and mitomycin-C seems to effectively stabilize disease progression in heavily pre-treated patients with metastatic colorectal cancer with a manageable safety profile. No significant financial relationships to disclose.

The distress thermometer predicts subjective, but not objective, cognitive complaints six months after treatment initiation in cancer patients

ABSTRACT Objectives: Research has indicated that cancer-related cognitive impairments (CRCI) may be influenced by psychosocial factors such as distress, worry and fatigue. Therefore, we aimed to validate the distress thermometer (DT) as a screening tool to detect CRCI six months post-treatment-initiation in a group of general cancer patients. Methods: Patients (≥18 years, n = 125) with a histologically confirmed diagnosis of a solid cancer or hematological malignancy, scheduled for a curative treatment, were evaluated at baseline (T0) and six months post-treatment-initiation (T1) for CRCI by a neuropsychological assessment, including patient-reported outcome measures (PROMs). Assessed cognitive domains included premorbid intelligence, attention, processing speed, flexibility, verbal and visual episodic memory and verbal fluency. PROMs entailed distress (DT, cut-off ≥4, range 0–10), anxiety and depression, fatigue (FACIT-fatigue scale) and subjective cognitive complaints. Results: At T0, 60.4% of patients showed a DT score of ≥4, whereas 50% met this criterion at T1. According to the definition of the International Cognition and Cancer Task Force, 25.5% and 28.3% of patients presented with a CRCI at T0 and T1, respectively. When evaluating the DT as a screening tool for CRCI at T1, data showed an inverse relationship between the DT and CRCI. ROC-curve analysis revealed an AUC <0.5. ROC-curve analyses evaluating the DT and FACIT-fatigue scale as screening tools for subjective cognitive complaints showed an AUC ± SE of, respectively, 0.642 ± 0.067 and 0.794 ± 0.057. Conclusions: The DT at T0 cannot be used to screen for objective CRCI at T1, but both the DT and FACIT-fatigue scale at T0 showed potential as screening tools for subjective cognitive complaints at T1.

Integrating geriatric assessment in the first line chemotherapy treatment in older patients with metastatic colorectal cancer: Results of a prospective observational cohort study (AVAPLUS)

OBJECTIVES This study aims to investigate the use of chemotherapy with or without bevacizumab in older patients with metastatic colorectal cancer (mCRC) in current daily practice and to identify predictive parameters for treatment-related outcomes. PATIENTS AND METHODS This is a Belgian multi-centre, observational cohort study. Patients≥70years old with mCRC considered suitable for first-line chemotherapy were eligible for inclusion. At baseline geriatric screening and assessment was performed. Treatment choice was at the discretion of the investigator. Treatment duration, Progression Free Survival (PFS) and safety were recorded. RESULTS Between August 2011 and July 2013, 252 patients with mCRC were included of which 50.8% were treated with bevacizumab. Median treatment duration was 5.5months and median PFS was 8.9months. Approximately 50% of patients experienced severe adverse events, most frequently diarrhea. In multivariate analysis, baseline Eastern Cooperative Oncology Group (ECOG)-performance status (PS) was predictive for treatment duration (p=0.0047), PFS (p<0.0001) and severe toxicity and baseline nutritional status for PFS (p=0.0007). In patients with a good ECOG-PS, nutritional status was predictive for PFS. CONCLUSIONS In current daily practice in Belgium, half of older patients with colorectal cancer treated with chemotherapy also receive bevacizumab. Nearly half of older patients presented with severe toxicity during treatment. Baseline nutritional status is a predictive marker for PFS. Patients with a baseline ECOG-PS≥2 have shorter PFS and higher risk of severe toxicity and should therefore be treated with caution.