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Sökning: WFRF:(Scheithauer W)

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1.
  • Bernhard, Jürg, et al. (författare)
  • Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone : a randomized multicenter phase III clinical trial--SAKK 44/00-CECOG/PAN.1.3.001
  • 2008
  • Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 26:22, s. 3695-3701
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To compare clinical benefit response (CBR) and quality of life (QOL) in patients receiving gemcitabine (Gem) plus capecitabine (Cap) versus single-agent Gem for advanced/metastatic pancreatic cancer. PATIENTS AND METHODS: Patients were randomly assigned to receive GemCap (oral Cap 650 mg/m(2) twice daily on days 1 through 14 plus Gem 1,000 mg/m(2) in a 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000 mg/m(2) in a 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and then weekly for 3 weeks every 4 weeks) for 24 weeks or until progression. CBR criteria and QOL indicators were assessed over this period. CBR was defined as improvement from baseline for >or= 4 consecutive weeks in pain (pain intensity or analgesic consumption) and Karnofsky performance status, stability in one but improvement in the other, or stability in pain and performance status but improvement in weight. RESULTS: Of 319 patients, 19% treated with GemCap and 20% treated with Gem experienced a CBR, with a median duration of 9.5 and 6.5 weeks, respectively (P < .02); 54% of patients treated with GemCap and 60% treated with Gem had no CBR (remaining patients were not assessable). There was no treatment difference in QOL (n = 311). QOL indicators were improving under chemotherapy (P < .05). These changes differed by the time to failure, with a worsening 1 to 2 months before treatment failure (all P < .05). CONCLUSION: There is no indication of a difference in CBR or QOL between GemCap and Gem. Regardless of their initial condition, some patients experience an improvement in QOL on chemotherapy, followed by a worsening before treatment failure.
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2.
  • Bernhard, J., et al. (författare)
  • Estimating prognosis and palliation based on tumour marker CA 19-9 and quality of life indicators in patients with advanced pancreatic cancer receiving chemotherapy
  • 2010
  • Ingår i: British Journal of Cancer. - 0007-0920 .- 1532-1827. ; 103:9, s. 1318-1324
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: To investigate the prognostic value of quality of life (QOL) relative to tumour marker carbohydrate antigen (CA) 19-9, and the role of CA 19-9 in estimating palliation in patients with advanced pancreatic cancer receiving chemotherapy. METHODS: CA 19-9 serum concentration was measured at baseline and every 3 weeks in a phase III trial (SAKK 44/00-CECOG/PAN.1.3.001). Patients scored QOL indicators at baseline, and before each administration of chemotherapy (weekly or bi-weekly) for 24 weeks or until progression. Prognostic factors were investigated by Cox models, QOL during chemotherapy by mixed-effect models. RESULTS: Patient-rated pain (P<0.02) and tiredness (P<0.03) were independent predictors for survival, although less prognostic than CA 19-9 (P<0.001). Baseline CA 19-9 did not predict QOL during chemotherapy, except for a marginal effect on pain (P<0.05). Mean changes in physical domains across the whole observation period were marginally correlated with the maximum CA 19-9 decrease. Patients in a better health status reported the most improvement in QOL within 20 days before maximum CA 19-9 decrease. They indicated substantially less pain and better physical well-being, already, early on during chemotherapy with a maximum CA 19-9 decrease of >= 50% vs <50%. CONCLUSION: In advanced pancreatic cancer, pain and tiredness are independent prognostic factors for survival, although less prognostic than CA 19-9. Quality of life improves before best CA 19-9 response but the maximum CA 19-9 decrease has no impact on subsequent QOL. To estimate palliation by chemotherapy, patient's perception needs to be taken into account.
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3.
  • Herrmann, Richard, et al. (författare)
  • Gemcitabine plus capecitabine compared with gemcitabine alone in advanced pancreatic cancer : a randomized, multicenter, phase III trial of the Swiss Group for Clinical Cancer Research and the Central European Cooperative Oncology Group
  • 2007
  • Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 25:16, s. 2212-2217
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: This phase III trial compared the efficacy and safety of gemcitabine (Gem) plus capecitabine (GemCap) versus single-agent Gem in advanced/metastatic pancreatic cancer. Patients and Methods: Patients were randomly assigned to receive GemCap (oral capecitabine 650 mg/m2 twice daily on days 1 to 14 plus Gem 1,000 mg/m2 by 30-minute infusion on days 1 and 8 every 3 weeks) or Gem (1,000 mg/m2 by 30-minute infusion weekly for 7 weeks, followed by a 1-week break, and then weekly for 3 weeks every 4 weeks). Patients were stratified according to center, Kamofsky performance score (KPS), presence of pain, and disease extent. Results: A total of 319 patients were enrolled between June 2001 and June 2004. Median overall survival (OS) time, the primary end point, was 8.4 and 7.2 months in the GemCap and Gem arms, respectively (P = .234). Post hoc analysis in patients with good KPS (score of 90 to 100) showed a significant prolongation of median OS time in the GemCap arm compared with the Gem arm (10.1 v 7.4 months, respectively; P = .014). The overall frequency of grade 3 or 4 adverse events was similar in each arm. Neutropenia was the most frequent grade 3 or 4 adverse event in both arms. Conclusion: GemCap failed to improve OS at a statistically significant level compared with standard Gem treatment. The safety of GemCap and Gem was similar. In the subgroup of patients with good performance status, median OS was improved significantly. GemCap is a practical regimen that may be considered as an alternative to single-agent Gem for the treatment of advanced/metastatic pancreatic cancer patients with a good performance status.
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4.
  • Nordlinger, Bernard, et al. (författare)
  • Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983) : a randomised controlled trial.
  • 2008
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 371:9617, s. 1007-1016
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Surgical resection alone is regarded as the standard of care for patients with liver metastases from colorectal cancer, but relapse is common. We assessed the combination of perioperative chemotherapy and surgery compared with surgery alone for patients with initially resectable liver metastases from colorectal cancer. Methods This parallel-group study reports the trial's final data for progression-free survival for a protocol unspecified interim time-point, while overall survival is still being monitored. 364 patients with histologically proven colorectal cancer and up to four liver metastases were randomly assigned to either six cycles of FOLFOX4 before and six cycles after surgery or to surgery alone (182 in perioperative chemotherapy group vs 182 in surgery group). Patients were centrally randomised by minimisation, adjusting for Centre and risk score. The primary objective was to detect a hazard ratio (HR) of 0.71 or less for progression-free survival. Primary analysis was by intention to treat. Analyses were repeated for all eligible (171 vs 171) and resected patients (151 vs 152). This trial is registered with ClinicalTrials.gov, number NCT00006479. Findings In the perioperative chemotherapy group, 151 (83%) patients were resected after a median of six (range 1-6) preoperative cycles and 115 (63%) patients received a median six (1-8) postoperative cycles. 152 (84%) patients were resected in the surgery group. The absolute increase in rate of progression-free survival at 3 years was 7.3% (from 28.1% [95-66% CI 21.3-35.51 to 35.4% [28.1-42.7]; HR 0 . 79 [0.62-1.02]; p=0.058) in randomised patients; 8 . 1% (from 28.1% [21.2-36.6] to 36.2% [28.7-43.8]; HR 0 . 77 [0-60-1 . 001; p=0 . 041) in eligible patients; and 9.2% (from 33.2% [25.3-41.2] to 42.4% [34.0-50.5]; HR 0.73 [0.55-0.97]; p=0.025) in patients undergoing resection. 139 patients died (64 in perioperative chemotherapy group vs 75 in surgery group). Reversible postoperative complications occurred more often after chemotherapy than after surgery (40/159 [25%] vs 27/170 [16%]; p=0.04). After surgery we recorded two deaths in the surgery alone group and one in the perioperative chemotherapy group. Interpretation Perioperative chemotherapy with FOLFOX4 is compatible with major liver surgery and reduces the risk of events of progression-free survival in eligible and resected. patients. Funding Swedish Cancer Society, Cancer Research UK, Ligue Nationale Contre le Cancer, US National Cancer Institute, Sanofi-Aventis.
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5.
  • Schmoll, H. J., et al. (författare)
  • ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making
  • 2012
  • Ingår i: Annals of Oncology. - 0923-7534 .- 1569-8041. ; 23:10, s. 2479-2516
  • Tidskriftsartikel (refereegranskat)abstract
    • Colorectal cancer (CRC) is the most common tumour type in both sexes combined in Western countries. Although screening programmes including the implementation of faecal occult blood test and colonoscopy might be able to reduce mortality by removing precursor lesions and by making diagnosis at an earlier stage, the burden of disease and mortality is still high. Improvement of diagnostic and treatment options increased staging accuracy, functional outcome for early stages as well as survival. Although high quality surgery is still the mainstay of curative treatment, the management of CRC must be a multi-modal approach performed by an experienced multi-disciplinary expert team. Optimal choice of the individual treatment modality according to disease localization and extent, tumour biology and patient factors is able to maintain quality of life, enables long-term survival and even cure in selected patients by a combination of chemotherapy and surgery. Treatment decisions must be based on the available evidence, which has been the basis for this consensus conference-based guideline delivering a clear proposal for diagnostic and treatment measures in each stage of rectal and colon cancer and the individual clinical situations. This ESMO guideline is recommended to be used as the basis for treatment and management decisions.
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8.
  • Garatti, A. Caratti o., et al. (författare)
  • The GRAVITY young stellar object survey: II. First spatially resolved observations of the CO bandhead emission in a high-mass YSO
  • 2020
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 635
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The inner regions of the discs of high-mass young stellar objects (HMYSOs) are still poorly known due to the small angular scales and the high visual extinction involved. Aims. We deploy near-infrared spectro-interferometry to probe the inner gaseous disc in HMYSOs and investigate the origin and physical characteristics of the CO bandhead emission (2.3-2.4 m). Methods. We present the first GRAVITY/VLTI observations at high spectral (R = 4000) and spatial (mas) resolution of the CO overtone transitions in NGC2024 IRS 2. Results. The continuum emission is resolved in all baselines and is slightly asymmetric, displaying small closure phases (8). Our best ellipsoid model provides a disc inclination of 34 1, a disc major axis position angle (PA) of 166 1, and a disc diameter of 3:99 0:09 mas (or 1.69 0.04 au, at a distance of 423 pc). The small closure phase signals in the continuum are modelled with a skewed rim, originating from a pure inclination effect. For the first time, our observations spatially and spectrally resolve the first four CO bandheads. Changes in visibility, as well as differential and closure phases across the bandheads are detected. Both the size and geometry of the CO-emitting region are determined by fitting a bidimensional Gaussian to the continuum-compensated CO bandhead visibilities. The CO-emitting region has a diameter of 2.740:08 0:07 mas (1.16 0.03 au), and is located in the inner gaseous disc, well within the dusty rim, with inclination and PA matching the dusty disc geometry, which indicates that both dusty and gaseous discs are coplanar. Physical and dynamical gas conditions are inferred by modelling the CO spectrum. Finally, we derive a direct measurement of the stellar mass of M 14:7 M by combining our interferometric and spectral modelling results.
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9.
  • Garcia-Lopez, R., et al. (författare)
  • A measure of the size of the magnetospheric accretion region in TW Hydrae
  • 2020
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 584:7822, s. 547-550
  • Tidskriftsartikel (refereegranskat)abstract
    • Stars form by accreting material from their surrounding disks. There is a consensus that matter flowing through the disk is channelled onto the stellar surface by the stellar magnetic field. This is thought to be strong enough to truncate the disk close to the corotation radius, at which the disk rotates at the same rate as the star. Spectro-interferometric studies in young stellar objects show that hydrogen emission (a well known tracer of accretion activity) mostly comes from a region a few milliarcseconds across, usually located within the dust sublimation radius1–3. The origin of the hydrogen emission could be the stellar magnetosphere, a rotating wind or a disk. In the case of intermediate-mass Herbig AeBe stars, the fact that Brackett γ (Brγ) emission is spatially resolved rules out the possibility that most of the emission comes from the magnetosphere4–6 because the weak magnetic fields (some tenths of a gauss) detected in these sources7,8 result in very compact magnetospheres. In the case of T Tauri sources, their larger magnetospheres should make them easier to resolve. The small angular size of the magnetosphere (a few tenths of a milliarcsecond), however, along with the presence of winds9,10 make the interpretation of the observations challenging. Here we report optical long-baseline interferometric observations that spatially resolve the inner disk of the T Tauri star TW Hydrae. We find that the near-infrared hydrogen emission comes from a region approximately 3.5 stellar radii across. This region is within the continuum dusty disk emitting region (7 stellar radii across) and also within the corotation radius, which is twice as big. This indicates that the hydrogen emission originates in the accretion columns (funnel flows of matter accreting onto the star), as expected in magnetospheric accretion models, rather than in a wind emitted at much larger distance (more than one astronomical unit).
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10.
  • Hess, Viviane, et al. (författare)
  • CA 19-9 tumour-marker response to chemotherapy in patients with advanced pancreatic cancer enrolled in a randomised controlled trial
  • 2008
  • Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 9:2, s. 132-8
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Several studies in patients undergoing chemotherapy for advanced pancreatic carcinoma have linked a decrease in the concentration of the tumour marker carbohydrate antigen (CA) 19-9 to lengthened survival. The aim of this study was to test the hypotheses that an early decrease in baseline serum CA 19-9 concentration (on day 42, after two cycles of chemotherapy) by at least 50% is associated with lengthened survival, and that a decrease in CA 19-9 concentration of at least 50% from the baseline concentration to the lowest value measured at any time during treatment (nadir) is of prognostic significance, enabling its use as a surrogate endpoint for survival. METHODS: CA 19-9 serum concentration was measured at baseline and every 3 weeks thereafter in patients with histologically proven advanced pancreatic carcinoma enrolled in a randomised trial of gemcitabine versus gemcitabine plus capecitabine. Patients were excluded if baseline serum CA 19-9 concentration was below the upper limit of normal (ULN) in the laboratory or if this measurement was missing. Comparisons of survival between patients with and without a CA 19-9 response were corrected for the guarantee-time bias by the landmark method. The trial on which this study is based is registered on the clinical trials site of the US National Cancer Institute website http://www.clinicaltrials.gov/ct/show/NCT00030732. FINDINGS: 247 of 319 randomised patients were assessable for analysis of baseline serum CA 19-9 concentration, and, of these, 175 patients were assessable for tumour-marker response to treatment. Median overall survival for patients with a baseline CA 19-9 concentration equal to or above the median value (ie, 59xULN) was 5.8 months (95% CI 5.1-7.0), which was significantly shorter than that for patients with baseline concentrations below the median value (10.3 months [95% CI 8.6-12.8], p<0.0001). An early decrease in CA 19-9 concentration of at least 50% after two cycles of chemotherapy was not associated with a longer overall survival compared with patients who did not have a decrease of at least 50% (median 10.1 months [9.2-12.7] vs 8.6 months [6.9-11.2], p=0.53; hazard ratio for death 1.11 [0.81-1.52]). Furthermore, a decrease in CA 19-9 concentration of at least 50% reached at the CA 19-9 nadir concentration was not associated with a longer overall survival compared with those patients who did not have a decrease of at least 50% (median 7.8 months [6.5.10.1] vs 6.7 months [5.5-9.8], p=0.74; 0.95 [0.69-1.31]) after adjusting for the guarantee-time bias. INTERPRETATION: Pretreatment serum CA 19-9 concentration is an independent prognostic factor for survival, but a decrease in concentration during chemotherapy is not significantly associated with lengthened survival compared with those who did not have a corresponding decrease. Our data suggest that CA 19-9 response during chemotherapy is not a valid surrogate endpoint for survival in clinical trials.
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