| 61. |
- Berndt, Sonja I., et al.
(författare)
-
Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia
- 2013
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:8, s. 868-U202
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P = 1.22 x 10(-14)), 18q21.33 (BCL2, P = 7.76 x 10(-11)), 11p15.5 (C11orf21, P = 2.15 x 10(-10)), 4q25 (LEF1, P = 4.24 x 10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P = 2.50 x 10(-9)), 9p21.3 (CDKN2B-AS1, P = 1.27 x 10(-8)), 18q21.32 (PMAIP1, P = 2.51 x 10(-8)), 15q15.1 (BMF, P = 2.71 x 10(-10)) and 2p22.2 (QPCT, P = 1.68 x 10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P = 2.08 x 10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P = 5.40 x 10(-8)) and 5p15.33 (TERT, P = 1.92 x 10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.
|
|
| 62. |
- Berndt, Sonja I., et al.
(författare)
-
Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia
- 2016
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P = 2.55 x 10(-11)), 6p25.2 (rs73718779, SERPINB6, P = 1.97 x 10(-8)) and 3q28 (rs9815073, LPP, P = 3.62 x 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P = 1.00 x 10(-11)) in the combined analysis. We find suggestive evidence (P<5 x 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P = 7.19 x 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P = 2.12 x 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.
|
|
| 63. |
- 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.
|
|
| 64. |
- Bernhard, Juerg, et al.
(författare)
-
Clinical Benefit Response in Pancreatic Cancer Trials Revisited
- 2014
-
Ingår i: Oncology Research and Treatment. - : S. Karger AG. - 2296-5270 .- 2296-5262. ; 37:1-2, s. 42-48
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Clinical benefit response (CBR), based on changes in pain, Karnofsky performance status, and weight, is an established palliative endpoint in trials for advanced gastrointestinal cancer. We investigated whether CBR is associated with survival, and whether CBR reflects a wide-enough range of domains to adequately capture patients' perception. Methods: CBR was prospectively evaluated in an international phase III chemotherapy trial in patients with advanced pancreatic cancer (n = 311) in parallel with patient-reported outcomes (PROs). Results: The median time to treatment failure was 3.4 months (range: 0-6). The majority of the CBRs (n = 39) were noted in patients who received chemotherapy for at least 5 months. Patients with CBR (n = 62) had longer survival than non-responders (n = 182) (hazard ratio = 0.69; 95% confidence interval: 0.51-0.94; p = 0.013). CBR was predicted with a sensitivity and specificity of 77-80% by various combinations of 3 mainly physical PROs. A comparison between the duration of CBR (n = 62, median = 8 months, range = 4-31) and clinically meaningful improvements in the PROs (n = 100-116; medians = 9-11 months, range = 4-24) showed similar intervals. Conclusion: CBR is associated with survival and mainly reflects physical domains. Within phase III chemotherapy trials for advanced gastrointestinal cancer, CBR can be replaced by a PRO evaluation, without losing substantial information but gaining complementary information.
|
|
| 65. |
- 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. - : Springer Science and Business Media LLC. - 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.
|
|
| 66. |
- Bexe-Lindskog, Elinor, et al.
(författare)
-
A population-based cohort study on adherence to practice guidelines for adjuvant chemotherapy in colorectal cancer
- 2014
-
Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407 .- 1471-2407. ; 14, s. 948-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The value of adjuvant chemotherapy in colorectal cancer is well studied, and guidelines have been established. Little is known about how treatment guidelines are implemented in the everyday clinical setting. Methods: This national population-based study on nearly 34,000 patients with colorectal cancer evaluates the adherence to present clinical guidelines for adjuvant chemotherapy. Virtually all patients with colorectal cancer in Sweden during the years 2007-2012 and data from the Swedish Colorectal Cancer Registry were included. Results: In colon cancer stage III, adherence to national guidelines was associated with lower age, presence of multidisciplinary team (MDT) conference, low co-morbidity, and worse N stage. The MDT forum also affected whether or not high-risk stage II colon cancer patients were considered for adjuvant chemotherapy. Rectal cancer patients both in stage II and III were considered for adjuvant chemotherapy less often than colon cancer patients, but the same factors influenced the decision. Adjuvant chemotherapy was started later than eight weeks after surgery in 30% of colon cancer patients and in 38% of rectal cancer patients. Conclusions: In Sweden, the adherence to national guidelines for adjuvant chemotherapy in colon cancer stage III is acceptable in younger and healthier patients. MDT conferences are of major importance and affect whether patients are recommended for adjuvant chemotherapy. Special consideration needs to be given to certain subgroups of patients, particularly older patients and patients with poorly differentiated tumors. There is a need to shorten the waiting time until start of chemotherapy.
|
|
| 67. |
|
|
| 68. |
- Biggar, Robert J., et al.
(författare)
-
Immunoglobulin subclass levels in patients with non-Hodgkin lymphoma
- 2009
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:11, s. 2616-20
-
Tidskriftsartikel (refereegranskat)abstract
- Allergy/atopy has been suggested to protect against non-Hodgkin lymphoma (NHL) and specific IgE levels are decreased in patients with NHL. We speculated that all immunoglobulin subclass levels might be downregulated in NHL and examined levels of IgM, IgD, IgA, IgE, IgG and IgG(4) in 200 NHL patients and 200 age- and sex-matched controls. Patients with B-cell NHL of many types had consistently lower median immunoglobulin subclass levels than controls. In every subclass except IgD, about 10-15% of B-cell NHL patients had absolute levels below the 2.5 percentile of controls. Subclass levels correlated with each other and many patients had more than one significantly low level. Levels were lowest for IgG(4) and IgE. Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma had especially low total IgE levels. In other B-cell NHL types, total IgE levels were decreased to a similar extent as other immunoglobulin subclasses. In conclusion, low IgE levels are only part of a more generalized loss of immunoglobulins of all subtypes in a wide variety of B-cell NHL types. Low immunoglobulin levels appear to be a consequence of B-cell NHL presence, and we speculate about molecular mechanisms that could reduce all immunoglobulin subclasses in B-cell NHL.
|
|
| 69. |
- Biggar, Robert J., et al.
(författare)
-
Serum YKL-40 and interleukin 6 levels in Hodgkin lymphoma
- 2008
-
Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 14:21, s. 6974-8
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Serum levels of the inflammatory markers YKL-40 and interleukin 6 (IL-6) are increased in many conditions, including cancers. We examined serum YKL-40 and IL-6 levels in patients with Hodgkin lymphoma, a tumor with strong immunologic reaction to relatively few tumor cells, especially in nodular sclerosis Hodgkin lymphoma. EXPERIMENTAL DESIGN: We analyzed Danish and Swedish patients with incident Hodgkin lymphoma (N=470) and population controls from Denmark (n=245 for YKL-40; n=348 for IL-6). Serum YKL-40 and IL-6 levels were determined by ELISA, and log-transformed data were analyzed by linear regression, adjusting for age and sex. RESULTS: Serum levels of YKL-40 and IL-6 increased in Hodgkin lymphoma patients compared with controls (YKL-40, 3.6-fold; IL-6, 8.3-fold; both, P<0.0001). In pretreatment samples from pretreatment Hodgkin lymphoma patients (n=176), levels were correlated with more advanced stages (P(trend), 0.0001 for YKL-40 and 0.013 for IL-6) and in those with B symptoms; however, levels were similar in nodular sclerosis and mixed cellularity subtypes, by EBV status, and in younger (<45 years old) and older patients. Patients tested soon after treatment onset had significantly lower levels than pretreatment patients; however, even >or=6 months after treatment onset, serum YKL-40 and IL-6 levels remained significantly increased compared with controls. In patients who died (n=12), pretreatment levels for YKL-40 and IL-6 were higher than in survivors, although not statistically significantly. CONCLUSIONS: Serum YKL-40 and IL-6 levels were increased in untreated Hodgkin lymphoma patients and those with more advanced stages but did not differ significantly by Hodgkin lymphoma histology. Following treatment, serum levels were significantly lower.
|
|
| 70. |
- Birgegård, Gunnar, 1944-, et al.
(författare)
-
Evaluation of beta globin mRNA as an early marker of haemoglobin response to epoetin treatment
- 2007
-
Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 24:3, s. 318-322
-
Tidskriftsartikel (refereegranskat)abstract
- Approximately 60% of anaemic cancer patients respond to epoetin treatment. An early marker of response would be valuable in order to avoid ineffective treatment. We have previously shown that beta globin mRNA increases rapidly after epoetin beta treatment of healthy controls. In the present study we have evaluated whether a change of this marker during the first 2 weeks of epoetin treatment could predict later Hb response in anaemic cancer patients. Twenty cancer patients with Hb <11 g/dl received epoetin beta (NeoRecormon®) 10,000 IU three times weekly during 6 weeks. Hb, reticulocytes and β-globin mRNA were followed. The latter was measured quantitatively using PCR via the 5′ nuclease assay. Eleven patients responded with a Hb increase of >1 g/dl, nine were nonresponders. All responders increased in β-globin mRNA within 2 weeks, mean 7.7× base-line. With a cut-off of an increase of 3× base-line value, we obtained a specificity of 45% and a sensitivity of 91% for the prediction of a later increase of Hb >1 g/dl. With a cut-off of 4× base-line, the specificity increased to 66%, but the sensitivity decreased to 82%. Beta globin mRNA increases before Hb in all responding patients. However, some non-responding patients also show an increase, and there is a trade-off between specificity and sensitivity as the cut-off level is set at different levels. Compared to reticulocyte count, β-globin mRNA is more reliable in the individual patient, but the clinical usefulness of the assay needs to be evaluated in further studies.
|
|
