| 1. |
- Myrdal, Gunnar, et al.
(författare)
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Regional differences in treatment and outcome in non-small cell lung cancer : a population-based study (Sweden)
- 2009
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Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 63:1, s. 16-22
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Tidskriftsartikel (refereegranskat)abstract
- In the recent decade uniform treatment guidelines for non-small cell lung cancer (NSCLC) have been introduced in Sweden. The objective of this study was to examine time trends and differences in treatment intensity for NSCLC between county clinical centres in Central Sweden. A second aim was to investigate whether any differences in treatment of NSCLC were associated with differences in survival. 4345 patients with a diagnosis of NSCLC between 1995 and 2003 were identified in the population-based Lung Cancer Register of Central Sweden. Multivariate logistic regression was used to estimate odds ratios to analyse the likelihood of receiving different treatment modalities for NSCLC. Cox proportional hazard models estimating relative hazard ratios were used to identify factors related to death (by any cause). Of all patients, 33.4% received no treatment, and 17.5% underwent surgery. Between 1995 and 2003, the proportion of patients receiving chemotherapy rose from 14.6% to 55%. There were pronounced differences between county centres in treatment policies, especially concerning surgery and radiotherapy. The likelihood of receiving treatment for NSCLC was highest at county centre A where both surgical treatment and chemotherapy were given more often. Compared to this reference county, the risk of death was between 20% and 40% higher in the other counties after adjusting for age, stage, gender, time period, smoking status and histopathological type. When analyses were adjusted for treatment, county of residence was no longer a prognostic factor. Despite common guidelines there were marked differences in treatment activity between the counties. Treatment activity was associated with survival. Survival benefits may follow improvement in compliance to guidelines.
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| 2. |
- Albertsson, Maria, et al.
(författare)
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Phase II studies on docetaxel alone every third week, or weekly in combination with gemcitabine in patients with primary locally advanced, metastatic, or recurrent esophageal cancer
- 2007
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Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 24:4, s. 407-412
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The purpose of these studies was to compare efficacy and toxicity of docetaxel alone with the combination of gemcitabine and docetaxel for treatment of metastatic esophageal carcinoma. PATIENTS AND METHODS: These studies enrolled patients with histopathologically verified squamous cell carcinoma or adenocarcinoma of the esophagus or cardia. Between March 1997 and June 1999, 52 patients were enrolled in the initial Phase II study (Study 1). They were scheduled for treatment with docetaxel 100 mg/m2 every third week as a 1-h infusion. The second Phase II study between September 2000 and March 2003 included 65 patients (Study II). They were given docetaxel 30 mg/m2, administered as a 30-min i.v. infusion weekly for four times, followed by 2 weeks of rest, and gemcitabine starting with a dose of 750 mg/m2 (if well-tolerated 1,000 mg/m2) on days 1 and 15, followed by 3 weeks of rest. A new cycle began on day 36. Patients were premedicated with betamethasone 8 mg p.o. on the evening before, and 8 mg i.v. 30-60 min before the docetaxel infusion. Response was confirmed by computed tomography and assessed at 12 and 24 weeks. Toxicity was assessed according to WHO scales. RESULTS: In study I, 38 out of the 52 enrolled patients were valuable. Two patients experienced complete remission (CR) (5%), 10 patients partial remission (PR) (26%), nine patients stable disease (SD) (24%), and 17 patients showed progressive disease (PD) (45%). Toxicity mainly involved leukopenia, which in some cases required hospitalization and treatment with antibiotics. In Study II, 46 out of the 65 enrolled patients (70%) were assessable. Out of these, three patients (7%) had CR, eight patients (17%) had PR, 10 patients (22%) had SD, and 25 (54%) PD. Overall response was 24% while an additional 22% showed stable disease. Toxicity mainly consisted of leucopenia and pain. CONCLUSION: Docetaxel as a single agent is active in esophageal cancer, both in treatment naive and in previously treated patients with recurrent disease. The overall response rate was 31%, with a good-safety profile. The addition of gemcitabine is well tolerated, but adds no efficacy. Weekly administration of docetaxel may be less effective. It demonstrates moderate efficacy and the doses used provide an acceptable safety profile.
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| 3. |
- Bolander, Åsa, 1977-
(författare)
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Prognostic Factors in Malignant Melanoma
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Because of the failure so far to find effective treatment for patients with advanced stages of melanoma, increasing efforts have been made to find prognostic factors identifying patients in the risk zone for development of metastasis.This thesis investigates the prognostic powers of a few selected serological and immunohistochemical biomarkers.In the first and second study, patients operated on for localized malignant melanoma were investigated regarding the prognostic impact of angiogenic serological markers and circulating levels of S100. We concluded that the S100 assays, especially S100BB, are potential biomarkers in patients with malignant melanoma, correlated to both survival and disease free survival. However, no such conclusion could be drawn from the first study, where we found no correlation to survival and investigated angiogenic markers.In the third and fourth study four new potential immunohistochemical biomarkers where investigated in collaboration with the Swedish Human Protein Atlas Program, and those where TRP-1, galectin-1, DLG5 and syntaxin-7.We found that TRP-1 correlated inversely with tumor stage and galectin-1 correlated to Ki-67.DLG5 showed a significant inverse correlation to Ki67 and the expression of STX7 was inversely correlated to tumor stage, suggesting that decreased expression is associated with more aggressive tumors.None of the investigated markers in study III and IV correlated with disease free survival or overall survival.In the fifth and last study, we examined the expression of SOX10, a transcription factor, in different melanocytic lesions. Also, a proliferation assay was carried out in a human melanoma cell line. The results reveal the presence of SOX10 in different melanocytic lesions, with a weak inverse correlation to survival and a significant inverse correlation to T-stage. A significant decrease in proliferation rate for SOX10 silenced cells was found and our data also suggests an increased migratory response in SOX10 silenced cells.
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| 4. |
- Bolander, Åsa, et al.
(författare)
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Serological and immunohistochemical analysis of S100 and derivatives as markers for prognosis of newly operated malignant melanoma patients
- 2008
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Ingår i: Melanoma research. - 0960-8931 .- 1473-5636. ; 18:6, s. 412-419
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of cutaneous malignant melanoma is rising, and tumour markers are attracting attention as a possible alternative to clinical examination in the follow-up situation. S100 is the preferred marker for malignant melanoma, and correlation between serum S100 and disease relapse and survival has been reported. S100 tests previously used in clinical studies were specified poorly regarding reactivity with S100A1B and S100BB. In this study, a newly designed S100 assay (designed to measure exclusively S100A1B and S100BB) and two newly developed serological assays, S100A1B, and S100BB, were investigated postoperatively in patients undergoing radical surgery for cutaneous malignant melanoma. Additionally, immunohistochemical analysis of S100A4 was performed on the primary malignant melanoma using tissue microarrays. The primary aim of the study was to investigate whether any of these assays, either singly or in combination, can contribute additional information concerning increased risk of relapse and death because of malignant melanoma. In total, 98 patients (54 males, 44 females) with malignant melanoma were included in the study. As a continuous variable, S100BB (P=0.016) was associated statistically with increased risk of relapse; this was not the case for increased values of either S100 (P=0.11) or S100A1B (P=0.92). The Kaplan-Meier overall survival as well as disease specific survival curve for the S100 serum level demonstrated a statistically significant association with better survival if the patient had a S100 level
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| 5. |
- Bolander, Åsa, et al.
(författare)
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The Role of Circulating Angiogenic Factors in Patients Operated on for Localized Malignant Melanoma
- 2007
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Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 27:5A, s. 3211-3217
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Tidskriftsartikel (refereegranskat)abstract
- Malignant melanoma is a disease capable of rapid progression and rapidly developing metastases. Angiogenesis is a key event signalling tumour progression and elevated levels of angiogenic markers may indicate metastatic disease. No previously published work has, so far, examined plasma vascular endothelial growth factor (VEGF) and its receptor, VEGFR-1, in melanoma. This study investigated circulating levels of the angiogenic factors, VEGF-A and -D, their receptors 1-3 and hepatocyte growth factor (HGF)/scatter factor, in patients shortly after primary surgery for localized malignant melanoma. Elevated circulating levels of VEGF and its receptors, and of HGF, were found postoperatively, possibly derived from the reactive stroma adjacent to the tumours. Using univariate analysis, a correlation between levels of VEGFR-1 and relapse was found, but a correlation between the investigated angiogenic factors and survival could not be established. The results of the present study indicate that production of these angiogenic factors may be due to sources other than malignant melanoma cells.
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| 6. |
- Carlsson, Björn, et al.
(författare)
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Effector T cell analysis of melanoma tumor-infiltrating lymphocyte cultures using HLA-ABC semimatched melanoma cell lines
- 2008
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Ingår i: Journal of immunotherapy (1997). - 1524-9557 .- 1537-4513. ; 31:7, s. 633-43
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Tidskriftsartikel (refereegranskat)abstract
- The generation of T cells with specific reactivity against tumor-associated antigens is prerequisite for adoptive transfer therapy. Melanoma-specific lymphocyte cultures can be established from tumor-infiltrating lymphocytes (TILs) by in vitro culture with high levels of interleukin-2. In this report, we present TIL data originating from 728 attempted cultures from 33 consecutive melanoma biopsy specimens originating from 30 patients. Cultures were analyzed for the presence of interferon gamma (IFNgamma)-producing cells upon stimulation with a panel of HLA-ABC semimatched melanoma cell lines. We sought to find whether such cell lines could be used to analyze TIL reactivity. Cell lines were used as stimulators to circumvent the need for autologous primary tumor cells. Melanoma-reactive cultures were identified by flow cytometry in 25 of the 30 patients. Four hundred forty-four of 728 (60.9%) cultures contained TILs at the end of experiment. Ninety-one of 318 cultures (28.6%) contained IFNgamma-producing cells after stimulation. In HLA-A*0201 patients IFNgamma analysis was complemented with melanoma-specific tetramer staining. All but one HLA-A*0201 patient had MART-1/Melan-A27-35-directed TILs, with frequencies ranging from 0.1% to 90% of CD8 cells. In addition, tetramer analysis also identified TILs directed against gp100, Tyrosinase, and Her2Neu. Tumor material was collected via needle biopsy in 16 cases and surgery in 18 cases. Overall, surgical material generated more cultures positive for T cells. The described methods are efficient in characterizing clinically relevant melanoma-reactive TILs.
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| 7. |
- Dreilich, M., et al.
(författare)
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HER-2 overexpression (3+) in patients with squamous cell esophageal carcinoma correlates with poorer survival
- 2006
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Ingår i: Dis Esophagus. - : Oxford University Press (OUP). ; 19:4, s. 224-231
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of esophageal carcinoma is increasing worldwide. In Sweden, approximately 400 patients are diagnosed each year. The present study retrospectively investigates survival in 97 patients with esophageal carcinoma in regard to their HER-2 status as examined by immunohistochemistry (IHC) and chromogen in situ hybridization (CISH). Sixty-eight patients had localised disease and 29 patients had advanced disease. Seventy patients had squamous cell carcinoma, and nine of these patients (13%) had HER-2 overexpression (3+). Eight (30%) of 27 adenocarcinoma patients overexpressed (3+) HER-2. In patients overexpressing (3+) HER-2 a statistical trend towards poorer survival was observed (P = 0.057). In squamous cell carcinoma patients, HER-2 overexpression (3+) correlated with poorer survival (P = 0.035), whereas in adenocarcinoma patients, HER-2 status (3+) did not. HER-2 amplification according to CISH was present in five (two squamous cell carcinomas and three adenocarcinomas) out of 17 HER-2 overexpressing (3+) tumours. In conclusion, HER-2 overexpression (3+) seems to be associated with poorer survival in esophageal carcinomas, especially in patients with squamous cell esophageal carcinoma.
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| 8. |
- Dreilich, Martin, 1970-
(författare)
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Predictive Factors in Esophageal Carcinoma
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Esophageal carcinoma is a malignancy with a poor prognosis and is the sixth cause of cancer related death worldwide. In Sweden approximately 400 new cases are diagnosed every year. The aim of this present thesis was to investigate predictive factors for esophageal carcinoma patients.126 esophageal carcinoma patients admitted to the department of Oncology at the University Hospital in Uppsala between 1990-2000 were investigated with focus on known and potential prognostic factors. Performance status and stage of the disease were the only independent prognostic factors (p-values <0.001). Angiogenic factors VEGF and bFGF were correlated to platelet and leukocyte counts and VEGF was correlated to tumor volume (p=0.04) whereas bFGF was not (p=0.08) in pre-treatment serum samples from 42 esophageal carcinoma patients. The use of the angiogenic factors as prognostic factors, prior to therapy in patients with esophageal carcinoma, according to the results from the present study, seems limited. HER-2 overexpression was seen in 17% of 97 investigated esophageal tumor samples. In squamous cell carcinoma patients, HER-2 overexpression correlated with poorer survival (p=0.035), whereas in adenocarcinoma patients, HER-2 status did not. HER-2 overexpression seems to be associated with poorer survival in esophageal carcinomas, especially in patients with squamous cell esophageal carcinoma. Telomerase activity was detected in all esophageal cell lines, with a broad range of activity levels. No correlation was found between telomerase activity levels and sensitivity to investigated cytotoxic drugs. We therefore conclude that basal telomerase activity level is not a key determinant of sensitivity to standard cytotoxic drugs in esophageal carcinoma cell lines. The virus HPV-16 was detected in 16 % of the patients; no other type HPV was detected. HPV-16 infection had no significant effect on survival (p=0.72). Our results did not show that HPV-16 increases survival or improve therapy response in patients with esophageal carcinoma.
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| 9. |
- Dreilich, Martin, et al.
(författare)
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Telomerase activity is not a key determinant of sensitivity to standard cytotoxic drugs in human esophageal carcinoma cell lines
- 2006
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Ingår i: Anti-Cancer Drugs. - 0959-4973 .- 1473-5741. ; 17:5, s. 503-509
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to investigate if basal telomerase activity levels may predict sensitivity to cytotoxic drugs in a panel of human esophageal carcinoma cell lines. The TRAPeze telomerase detection assay was used to investigate telomerase activity in the cell lines. Cytotoxic drug sensitivity for 20 standard cytotoxic agents was assessed using the fluorometric microculture cytotoxicity assay (FMCA). Telomerase activity was detected in all cell lines with a broad range of activity levels. Drug sensitivity also varied considerably between the cell lines. Except for a P value towards a correlation between mitoxantrone and telomerase activity (P=0.054), no statistically significant correlation was found between telomerase activity levels and sensitivity to investigated drugs, including key drugs such as cisplatin (P=0.9), 5-fluorouracil (P=0.8) and doxorubicin (P=0.54). We therefore conclude that basal telomerase activity level is not a key determinant of sensitivity to standard cytotoxic drugs in esophageal carcinoma cell lines.
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| 10. |
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