| 61. |
- Robinson, David, 1968-, et al.
(författare)
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PSA Kinetics Provide Improved Prediction of Survival in Metastatic Hormone-Refractory Prostate Cancer
- 2008
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Ingår i: Urology. - : Elsevier BV. - 0090-4295 .- 1527-9995. ; 72:4, s. 903-907
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To assess the value of prostate-specific antigen (PSA) kinetics in predicting survival and relate this to the baseline variables in men with metastatic hormone-refractory prostate cancer (HRPC). Methods: The data from 417 men with HRPC were included in a logistic regression model that included hemoglobin, PSA, alkaline phosphatase, Soloway score, and performance status pain analgesic score at baseline. The posttreatment variables included the PSA level halving time after the start of treatment, PSA level at nadir, interval to nadir, PSA velocity (PSAV), PSA doubling time after reaching a nadir, patient age, and treatment. These variables were added to the baseline model, forming new logistic regression models that were tested for net reclassification improvement. Results: The area under the receiver operating characteristics curve for the baseline model was 0.67. Of all variables related to PSA kinetics, the PSAV was the best predictor. The addition of PSAV to the baseline model increased the area under the receiver operating characteristics curve to 0.81. Only a moderate increase in the area under the receiver operating characteristics curve (0.83) was achieved by combining the baseline model in a multivariate model with PSAV, PSA doubling time, interval to nadir, and patient age at diagnosis of HRPC. Conclusions: The PSAV alone gave a better prediction of survival value than all other PSA kinetics variables. By combining PSAV with the variables available at baseline, a better ground for treatment decision-making in men with HRPC can be achieved.
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| 62. |
- Lövgren, Malin, et al.
(författare)
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Symptoms and problems with functioning among women and men with inoperable lung cancer : A longitudinal study.
- 2008
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Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 60:1, s. 113-124
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study is to compare the prevalence and intensity of symptoms and problems with functioning between women and men with inoperable lung cancer (LC) during 3 months post-diagnosis. One hundred and fifty-nine patients completed the EORTC QLQ C-30+LC13 at three time points: close to diagnosis and prior to treatment, and one, and 3 months later. Descriptive cross-sectional analyses and longitudinal analyses using repeated measure ANOVA were conducted. These patients reported many and intense symptoms and problems with functioning. The most salient finding from the cross-sectional analysis was that women reported both more, and more intense problems with emotional functioning close to diagnosis. Statistically significant improvements over time were found in both men and women with regard to emotional functioning, dyspnea, insomnia, cough, pain in arm/shoulder, while physical functioning, fatigue, constipation, dysphagia, peripheral neuropathy and alopecia deteriorated significantly over time. The longitudinal analyses suggest that, with the exception of emotional functioning, gender differences were not only related to biological sex alone, but were also found to be related to other components of the patients' life situation, such as education, age, civil status and type of LC. Sensitivity to different symptom experiences and responses to those experiences between and within women and men is also necessary in the management of symptoms in patients with inoperable LC.
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| 63. |
- Lövgren, Malin, et al.
(författare)
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Time spans from first symptom to treatment in patients with lung cancer : The influence of symptoms and demographic characteristics
- 2008
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X .- 0001-6381. ; 47:3, s. 397-405
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cancer stage at diagnosis is the most important prognostic factor for lung cancer (LC), but most patients are diagnosed with advanced disease with many and intense symptoms. This study explores relationships between LC patients' first symptoms, symptoms triggering health care system (HCS) contact, demographic/clinical characteristics, and time spans in the care trajectory from first symptom(s) to treatment start.MATERIALS AND METHODS: Medical records were examined from all 314 patients diagnosed with primary LC in 2003 at a Department of Respiratory Medicine, in Stockholm Sweden. Descriptive analysis was used to examine symptoms and time spans in the care trajectory. Cox regression analysis was conducted to explore the influence of symptoms and demographic/clinical characteristics on the time spans.RESULTS: Tumor-specific symptoms led to HCS visits to a greater extent than did systemic symptoms, despite reports of weight loss, fatigue and appetite loss as common first symptoms. Minor differences between women and men were found regarding specific symptoms. The study confirms that the time spans from first symptoms reported to treatment start are extensive, exceeding Swedish national recommendations. A lump/resistance, neurological symptoms, appetite loss, hemoptysis and non-thoracic related pain were associated with significantly shorter time spans in the care trajectory. People >74 years old risked longer time span from first HCS visit to treatment start.CONCLUSION: This study indicates a need for a more efficient LC care trajectory. Elderly patients could be particularly vulnerable for longer time spans.
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| 64. |
- Engström, Katarina, 1956, et al.
(författare)
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Liposarcoma: outcome based on the Scandinavian Sarcoma Group register.
- 2008
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Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 113:7, s. 1649-56
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim was to study the clinicopathological characteristics, treatment, and outcome of liposarcoma in an unselected, population-based patient sample, and to establish whether treatment was according to the Scandinavian Sarcoma Group (SSG) treatment guidelines. METHODS: The SSG Pathology Board reviewed 319 liposarcoma cases reported between 1986 and 1998. After the review, 237 patients without metastasis were analyzed for local recurrence rate in relation to surgical margins, radiotherapy, occurrence of metastasis, and survival. RESULTS: Seventy-eight percent of the patients were primarily operated on at a sarcoma center, 45% with wide margins. All patients operated on outside the center had nonwide margins. Low-grade lesions constituted 67% of cases. Despite nonwide surgery, only 58% of high-grade lesions were treated with postoperative radiotherapy. The risk of local recurrence after nonwide surgery, without irradiation, was 47% for high-grade lesions. The estimated 10-year, local recurrence-free and metastasis-free survival in the low-grade group was 87% and 95%, respectively. In the high-grade group, it was 75% and 61%, respectively. Independent adverse prognostic factors for local recurrence were surgery outside a sarcoma center and histological type dedifferentiated liposarcoma. For metastases, they were old age, large tumor size, high grade, and histological type myxoid liposarcoma with a round cell component. Radiotherapy showed significant effect on local recurrence rate for the same grade and margin. CONCLUSIONS: Patients with liposarcoma should be treated at specialized centers. Postoperative radiotherapy decreases the local recurrence rate. To maintain quality and provide support for further trials, reporting to quality registers is crucial.
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| 65. |
- Pontén, Fredrik, et al.
(författare)
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The Human Protein Atlas : A tool for pathology
- 2008
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 216:4, s. 387-393
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Tidskriftsartikel (refereegranskat)abstract
- Tissue-based diagnostics and research is incessantly evolving with the development of new molecular tools. It has long been realized that immunohistochemistry can add an important new level of information on top of morphology and that protein expression patterns in a cancer may yield crucial diagnostic and prognostic information. We have generated an immunohistochemistry-based map of protein expression profiles in normal tissues, cancer and cell lines. For each antibody, altogether 708 spots of tissues and cells are analysed and the resulting images and data are presented as freely available in the Human Protein Atlas (www.proteinatlas.org). The new version 4 of the atlas, including more than 5 million images of immunohistochemically stained tissues and cells, is based on 6122 antibodies, representing 5011 human proteins encoded by approximately 25% of the human genome. The gene-centric database includes a putative classification of proteins in various protein classes, both functional classes, such as kinases or transcription factors and project-related classes, such as candidate genes for cancer or cardiovascular diseases. For each of the internally generated antibodies, the exact antigen sequence is presented, together with a visualization of application-specific validation data, including a protein array assay, western blot analysis, immunohistochemistry and, in most cases, immunofluorescent-based confocal microscopy. The updated version also includes new search algorithms to allow complex queries regarding expression profiles, protein classes and chromosome location. Thus, the presented Human Protein Atlas provides a resource for pathology-based biomedical research, including protein science and biomarker discovery.
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| 66. |
- Thellenberg Karlsson, Camilla, 1972-
(författare)
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Prostate cancer : epidemiological studies of risk factors
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In spite of the fact that prostate cancer is the most common male cancer in both Sweden and many other countries in the developed world, little is known of risk factors and predisposing conditions. The only well recognized risk factors are age, race and familial aggregation. More knowledge about risk factors could lead to better preventive measures together with better treatments. One way to evaluate this is to study second primary cancers; the connection between two different cancers can give valuable insight in etiology or clues to shared risk factors. This thesis aims at evaluating risk factors for prostate cancer. We constructed a cohort of 135,713 men diagnosed with prostate cancer and reported to the Swedish Cancer Registry 1958-1996. The cohort was followed for second primary cancers and a doubled risk of male breast cancer was found. We also noted increased risks for small intestine cancers and melanoma. As a follow-up on the increased risk of male breast cancer, we performed a nested case – control study. Included cases were men with first prostate and then breast cancer (n = 41) matched to men with only prostate cancer (n =81). For these men, we collected medical records and extracted data regarding treatment. Furthermore, all men diagnosed with both prostate and breast cancer irrespective which came first (n = 83) were used as probands. To both these sets of cases with breast and prostate cancer, we identified first degree relatives and grandchildren from parish offices throughout Sweden. Linking to the Cancer Registry retrieved all cancer diagnoses amongst relatives. Results from this study show a relation between estrogen treatment of prostate cancer and the risk of developing breast cancer. We also found that a small part of the cases with both cancers appeared in families with inheritance patterns possibly attributed to BRCA2. As estrogen treatment seemed involved in increased risk of breast cancer after prostate cancer, we wanted to investigate the newly discovered Estrogen receptor β and the relation to prostate cancer risk. Previous reports have shown that ERβ acts as a negative regulator of proliferation. ERβ expression occurs mainly in prostatic epithelial cells and the expression gradually diminishes when cancer develops and aggravates. We used a single nucleotide polymorphism (SNP) association study approach to evaluate genetic variation in ERβ as a risk factor for prostate cancer. One SNP, located in the promoter region associated with a small increased risk of prostate cancer whereas variation in the rest of the gene did not. In the last paper, we investigated trans-urethral resection (TURP) of the prostate due to benign prostate hyperplasia (BPH) as a risk factor for later development of prostate cancer. Evidence has gathered that both BPH and prostate cancer are associated to inflammation. By comparing incidence and mortality in a cohort of 7,901 men with the general population there appeared to be an increased risk of prostate cancer but decreased mortality. Analyzing this increased risk further, we conducted a nested case - control study with men extracted from the cohort. Cases had a TURP and later developed prostate cancer and controls just had a TURP. We then evaluated the specimens from TURP regarding extent of inflammation, degree of androgen receptor down regulation and expression of p53, all factors previous associated with prostate cancer. None of these parameters differed between cases and controls and they can therefore not explain the increased risk. Decreased mortality but increased risk might be explained by surveillance bias, which means more medical attention to these patients, resulting in diagnosing clinically non-significant cancers. In summary, our results show a doubled risk of male breast cancer following prostate cancer. A risk that can be attributed to the use of estrogen to treat prostate cancer or to some extent a possible mutation in BRCA2. We also propose that a SNP change in the ERβ promoter confer a small increased risk of prostate cancer. A small risk elevation of prostate cancer following TURP most probable could depend on surveillance bias.
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| 67. |
- Fernö, Mårten, et al.
(författare)
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Analys av HER2 i bröstcancer kvalitetssäkrad. Viktig behandlingsprediktiv och prognostisk faktor.
- 2008
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 105:32-33, s. 2181-2184
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Tidskriftsartikel (refereegranskat)abstract
- Human epidermal growth factor receptor 2 (HER2) is overexpressed and/or amplified in 15-20% of all breast cancers, and is associated with an aggressive tumour type with impaired prognosis and a predictive marker for trastuzumab treatment. HER2 status can be determined by immunohistochemistry (IHC) at protein level and by fluorescence in situ hybridisation (FISH) analysing gene amplification, and it is recommended that it should be performed in all primary breast cancers. In a quality control study the reproducibility of HER2 status was assessed by distributing eleven breast tumours prepared on a tissue microarray to 25 pathology laboratories in Sweden in 2005 and 2006. The concordance between the laboratories indicated good reproducibility for IHC 2005 (kappa value 0.79) and very good reproducibility for 2006 (kappa value 0.86). The corresponding reproducibility for FISH was very good on both occasions (kappa value 0.92 and 0.96 respectively). A questionnaire indicated that 90% of all primary breast cancers diagnosed in Sweden in 2006 were tested for HER2 status. By way of summary, HER2 status is now implemented in clinical routine diagnostics in Sweden, and the present reproducibility study supports a high quality of testing.
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| 68. |
- Gunnarsson, Rebeqa, et al.
(författare)
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Screening for copy-number alterations and loss of heterozygosity in chronic lymphocytic leukemia-A comparative study of four differently designed, high resolution microarray platforms
- 2008
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 93, s. 0536-0536
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Tidskriftsartikel (refereegranskat)abstract
- Screening for gene copy-number alterations (CNAs) has improved by applying genome-wide microarrays, where SNP arrays also allow analysis of loss of heterozygozity (LOH). We here analyzed 10 chronic lymphocytic leukemia (CLL) samples using four different high-resolution platforms: BAC arrays (32K), oligonucleotide arrays (185K, Agilent), and two SNP arrays (250K, Affymetrix and 317K, Illumina). Cross-platform comparison revealed 29 concordantly detected CNAs, including known recurrent alterations, which confirmed that all platforms are powerful tools when screening for large aberrations. However, detection of 32 additional regions present in 2-3 platforms illustrated a discrepancy in detection of small CNAs, which often involved reported copy-number variations. LOH analysis using dChip revealed concordance of mainly large regions, but showed numerous, small nonoverlapping regions and LOH escaping detection. Evaluation of baseline variation and copy-number ratio response showed the best performance for the Agilent platform and confirmed the robustness of BAC arrays. Accordingly, these platforms demonstrated a higher degree of platform-specific CNAs. The SNP arrays displayed higher technical variation, although this was compensated by high density of elements. Affymetrix detected a higher degree of CNAs compared to Illumina, while the latter showed a lower noise level and higher detection rate in the LOH analysis. Large-scale studies of genomic aberrations are now feasible, but new tools for LOH analysis are requested.
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| 69. |
- Linderoth, Johan, et al.
(författare)
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Genes associated with the tumour microenvironment are differentially expressed in cured versus primary chemotherapy-refractory diffuse large B-cell lymphoma
- 2008
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Ingår i: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 141:4, s. 423-32
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Tidskriftsartikel (refereegranskat)abstract
- In order to identify genes associated with primary chemotherapy-resistance, gene expression profiles (GEP) in tumour tissue from 37 patients with de novo diffuse large B-cell lymphoma (DLBCL), stage II-IV, either in continuous complete remission (n = 24) or with progressive disease during primary treatment (n = 13), were examined using spotted 55K oligonucleotide arrays. Immunohistochemistry was used for confirmation at the protein level. The top 86 genes that best discriminated between the two cohorts were chosen for further analysis. Only seven of 86 genes were overexpressed in the refractory cohort, e.g. RABGGTB and POLE, both potential targets for drug intervention. Seventy-nine of 86 genes were overexpressed in the cured cohort and mainly coded for proteins expressed in the tumour microenvironment, many of them involved in proteolytic activity and remodelling of extra cellular matrix. Furthermore, major histocompatibility complex class I molecules, CD3D and ICAM1 were overexpressed, indicating an enhanced immunological reaction. Immunohistochemistry confirmed the GEP results. The frequency of tumour infiltrating lymphocytes, macrophages, and reactive cells expressing ICAM-1, lysozyme, cathepsin D, urokinase plasminogen activator receptor, signal transducer and activator of transcription 1, and galectin-3 was higher in the cured cohort. These findings indicate that a reactive microenvironment has an impact on the outcome of chemotherapy in DLBCL.
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| 70. |
- Mattsson, Elisabet, et al.
(författare)
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Are there any positive consequences of childhood cancer? : A review of the literature
- 2008
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Ingår i: Acta Oecologica. - : Informa UK Limited. - 1146-609X .- 1873-6238 .- 0284-186X .- 1651-226X. ; 47:2, s. 199-206
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Forskningsöversikt (refereegranskat)abstract
- The aim was to investigate whether there are any positive consequences of childhood cancer. Studies published 1990-2005 reporting survivors' descriptions of positive consequences of childhood cancer were identified through a search in the databases CINAHL, PsycINFO, and PubMed. According to a manifest content analysis, positive consequences were referred to three themes: life values, relations to others, and relation to self. A second search in the same databases was conducted to identify studies investigating whether survivors of childhood cancer differ from comparison groups with regard to variables assigned to these themes. In these studies, no conclusions about positive consequences with regard to the theme life values can be drawn, as only one study was identified. In addition, only a small minority of findings from comparative studies indicate that childhood cancer has any positive consequences with regard to relations to others and relation to self. A majority of the results indicate that survivors do not differ from comparison groups, whereas some findings highlight that friendship and marital status are areas of concern, and parenthood and sexuality are areas of potential concern. It is recommended that survivors of childhood cancer are followed up by a multi-professional team, focusing not only on the survivors' health status but also on relations to family, friends, and partners.
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