| 1. |
- Dahl, Christian Falk, et al.
(författare)
-
A controlled study of risk factors for disease and current problems in long-term testicular cancer survivors
- 2010
-
Ingår i: Journal of cancer survivorship. - : Springer Science and Business Media LLC. - 1932-2259 .- 1932-2267. ; 4:3, s. 256-265
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction To compare risk factors for disease and current problems in long-term testicular cancer survivors (TCSs) and age-matched population-based controls (NORMs). Methods The study was cross-sectional and concerned 1,291 Norwegian TCSs followed up after a mean of 11 years, and 6,455 NORMs. Both TCSs and NORMs completed questionnaires and had a clinical examination. Indices for risk factors and current problems were calculated. Outcome measures were: visits to general practitioners last year, poor self-rated health, and poor quality of life (QoL). Results The mean risk score was significantly lower and the mean current problem score significantly higher in TCSs compared to NORMs without reaching clinical significance. The risk for future fatal cardiac events did not differ between the groups. TCSs had a higher risk for visiting a general practitioner than NORMs (OR 3.58, 95% CI 3.09-4.15), while no significant difference was observed for self-rated health. Poor QoL in TCSs was significantly associated with more current problems than risk factors. Previous treatment for mental problems, presence of severe somatic disease and musculo-skeletal problems were significantly associated with all three outcome measures. Musculo-skeletal problems were most strongly associated with visits to general practitioners among TCSs. Conclusions Several risk factors for preventive clinical interventions and current problems that eventually should be treated were identified in TCSs. Implications for cancer survivors TCSs show several risk factors and current problems that are relevant for visits to general practitioners, poorer self-rated health, and poorer QoL. These should get attention from health personnel caring for TCSs.
|
|
| 2. |
- Tveit, Kjell Magne, et al.
(författare)
-
Phase III Trial of Cetuximab With Continuous or Intermittent Fluorouracil, Leucovorin, and Oxaliplatin (Nordic FLOX) Versus FLOX Alone in First-Line Treatment of Metastatic Colorectal Cancer : The NORDIC-VII Study
- 2012
-
Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology: JCO. - 0732-183X .- 1527-7755. ; 30:15, s. 1755-1762
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: The NORDIC-VII multicenter phase III trial investigated the efficacy of cetuximab when added to bolus fluorouracil/folinic acid and oxaliplatin (Nordic FLOX), administered continuously or intermittently, in previously untreated metastatic colorectal cancer (mCRC). The influence of KRAS mutation status on treatment outcome was also investigated. Patients and Methods: Patients were randomly assigned to receive either standard Nordic FLOX (arm A), cetuximab and FLOX (arm B), or cetuximab combined with intermittent FLOX (arm C). Primary end point was progression-free survival (PFS). Overall survival (OS), response rate, R0 resection rate, and safety were secondary end points. Results: Of the 571 patients randomly assigned, 566 were evaluable in intention-to-treat (ITT) analyses. KRAS and BRAF mutation analyses were obtained in 498 (88%) and 457 patients (81%), respectively. KRAS mutations were present in 39% of the tumors; 12% of tumors had BRAF mutations. The presence of BRAF mutations was a strong negative prognostic factor. In the ITT population, median PFS was 7.9, 8.3, and 7.3 months for the three arms, respectively (not significantly different). OS was almost identical for the three groups (20.4, 19.7, 20.3 months, respectively), and confirmed response rates were 41%, 49%, and 47%, respectively. In patients with KRAS wild-type tumors, cetuximab did not provide any additional benefit compared with FLOX alone. In patients with KRAS mutations, no significant difference was detected, although a trend toward improved PFS was observed in arm B. The regimens were well tolerated. Conclusion: Cetuximab did not add significant benefit to the Nordic FLOX regimen in first-line treatment of mCRC.
|
|
| 3. |
|
|
| 4. |
- Haugnes, Hege S., et al.
(författare)
-
High-dose chemotherapy with autologous stem cell support in patients with metastatic non-seminomatous testicular cancer : a report from the Swedish Norwegian Testicular Cancer Group (SWENOTECA)
- 2012
-
Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 51:2, s. 168-176
-
Tidskriftsartikel (refereegranskat)abstract
- Background. The SWENOTECA IV protocol from 1995 is a prospective population-based study in metastatic non-seminomatous germ cell testicular cancer (NSGCT), designed for early identification of patients with poor response to standard cisplatin-based chemotherapy. A slow tumor marker decline (HCG T(1/2) > 3 days, AFP T(1/2) > 7 days) after BEP or BEP plus ifosfamide was regarded as poor response. The aim of this study was to present survival and toxicity data for patients treated with high-dose chemotherapy (HDCT) within the SWENOTECA IV cancer care program. Material and methods. In total 882 adult men diagnosed with metastatic NSGCT between July 1995 and June 2007 in Sweden and Norway (except one center) were included in SWENOTECA IV and treated accordingly. Among these, 55 men (6.2%) were treated with HDCT according to three different indications in the protocol: A) poor response to standard-dose intensified chemotherapy (BEP plus ifosfamide); B) vital cancer at surgery after intensified chemotherapy; and C) selected relapses after previous chemotherapy. In situation A and C two HDCT cycles and in situation B one HDCT cycle was recommended. Situation A was the reason for HDCT in 36 patients, B in seven and C in 12 patients. The first HDCT cycle consisted of carboplatin 28 x (GFR + 25) mg, cyclofosfamide 6000 mg/m(2) and etoposide 1750 mg/m(2), administered over four days. In cycle two, etoposide was replaced by tiotepa 480 mg/m(2). Results. After a median follow-up of 7.5 years, overall survival was 72%, 100% and 58%, while failure-free survival was 64%, 71% and 42% in situation A, B and C, respectively. Three patients (5.5%) died during HDCT (renal failure or intracerebral hemorrhage). Nephrotoxicity was the most common non-hematological grade 4 toxicity (n = 5, 9%). Conclusion. The population-based SWENOTECA strategy, selecting patients who do not respond adequately to primary standard-dose chemotherapy for immediate treatment intensification with HDCT, is feasible and might be advantageous.
|
|
| 5. |
- Kilander, Michaela B. C., et al.
(författare)
-
Disheveled regulates precoupling of heterotrimeric G proteins to Frizzled 6
- 2014
-
Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 28:5, s. 2293-2305
-
Tidskriftsartikel (refereegranskat)abstract
- Frizzleds (FZDs) are classified as G-protein-coupling receptors, but how signals are initiated and specified through heterotrimeric G proteins is unknown. FZD(6) regulates convergent extension movements, and its C-terminal Arg511Cys mutation causes nail dysplasia in humans. We investigated the functional relationship between FZD(6), Disheveled (DVL), and heterotrimeric G proteins. Live cell imaging combined with fluorescence recovery after photobleaching (FRAP) revealed that inactive human FZD(6) precouples to G(i1) and G(q) but not to G(oA),G(s), and G(12) proteins. G-protein coupling is measured as a 10-20% reduction in the mobile fraction of fluorescently tagged G proteins on chemical receptor surface cross-linking. The FZD(6) Arg511Cys mutation is incapable of G-protein precoupling, even though it still binds DVL. Using both FRAP and Forster resonance energy transfer (FRET) technology, we showed that the FZD(6)-G(i1) and FZD-G(q) complexes dissociate on WNT-5A stimulation. Most important, G-protein precoupling of FZD(6) and WNT-5A-induced signaling to extracellular signal-regulated kinase1/2 were impaired by DVL knockdown or overexpression, arguing for a strict dependence of FZD(6)-G-protein coupling on DVL levels and identifying DVL as a master regulator of FZD/G-protein signaling. In summary, we propose a mechanistic connection between DVL and G proteins integrating WNT, FZD, G-protein, and DVL function.Kilander, M. B. C., Petersen, J., Andressen, K. W., Ganji, R. S. Levy, F. O., Schuster, J., Dahl N., Bryja, V., Schulte, G. Disheveled regulates precoupling of heterotrimeric G proteins to Frizzled 6.
|
|
| 6. |
- Leon, Otilia, et al.
(författare)
-
Anal carcinoma - Survival and recurrence in a large cohort of patients treated according to Nordic guidelines
- 2014
-
Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 113:3, s. 352-358
-
Tidskriftsartikel (refereegranskat)abstract
- Objective:To evaluate treatment outcome in a large population-based cohort of patients with anal cancer treated according to Nordic guidelines.Material:Clinical data were collected on 1266 patients with anal squamous cell carcinoma diagnosed from 2000 to 2007 in Sweden, Norway and Denmark. 886 of the patients received radiotherapy 5464 Gy with or without chemotherapy (5-fluorouracil plus cisplatin or mitomycin). according to different protocols, stratified by tumor stage.Results:High age, male gender, large primary tumor, lymph node metastases, distant metastases, poor performance status, and non-inclusion into a protocol were all independent factors associated with worse outcome. Among patients treated according to any of the protocols, the 3-year recurrence-free survival ranged from 63% to 76%, with locoregional recurrences in 17% and distant metastases in 11% of patients. The highest rate of inguinal recurrence (11%) was seen in patients with small primary tumors, treated without inguinal irradiation.Conclusions:Good treatment efficacy was obtained with Nordic, widely implemented, guidelines for treatment of anal cancer. Inguinal prophylactic irradiation should be recommended also for small primary tumors. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
|
|
| 7. |
- Olofsson, Sven-Erik, et al.
(författare)
-
Population-Based Study of Treatment Guided by Tumor Marker Decline in Patients With Metastatic Nonseminomatous Germ Cell Tumor : A Report From the Swedish-Norwegian Testicular Cancer Group
- 2011
-
Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 29:15, s. 2032-2039
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose From 1995 to 2003, 603 adult patients from Sweden and Norway with metastatic testicular nonseminomatous germ cell tumor (NSGCT) were included prospectively in a population-based protocol with strict guidelines for staging, treatment, and follow-up. Patients with extragonadal primary tumor or previous treatment for contralateral testicular tumor were excluded. The basic strategy was to individualize treatment according to initial tumor marker response. Methods Initial treatment for all patients was two courses of standard bleomycin, etoposide, and cisplatin (BEP), with tumor markers analyzed weekly. Good response was defined as a half-life (t(1/2)) for alpha-fetoprotein (AFP) of <= 7 days and/or for beta-human chorionic gonadotropin (beta-HCG) of <= 3 days. Patients with prolonged marker t(1/2) (ie, poor response) received intensification with addition of ifosfamide (BEP-if/PEI) in step 1. If poor response continued, the treatment was intensified with high-dose chemotherapy with stem-cell rescue as step 2. Results Overall, 99% of all patients with metastatic testicular NSGCT in the population were included in the protocol. Median follow-up was 8.2 years. Seventy-seven percent of the patients were treated with BEP alone; 18% received intensification step 1%, and 5% received intensification step 2. Grouped according to International Germ Cell Consensus Classification, 10-year overall survival was 94.7% in good-prognosis patients, 90.0% in intermediate-prognosis patients, and 67.4% in poor-prognosis patients. Conclusion With detailed treatment protocols and a dedicated collaborative group of specialists, treatment results comparable to those reported from large single institutions can be achieved at national level. With the treatment principles used in Swedish-Norwegian Testicular Cancer Group study SWENOTECA IV, the survival of intermediate-prognosis patients is remarkable and close to that of good-prognosis patients.
|
|
| 8. |
|
|
| 9. |
- Røsjø, Helge, et al.
(författare)
-
Secretogranin II; a Protein Increased in the Myocardium and Circulation in Heart Failure with Cardioprotective Properties
- 2012
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:5, s. e37401-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Several beneficial effects have been demonstrated for secretogranin II (SgII) in non-cardiac tissue. As cardiac production of chromogranin A and B, two related proteins, is increased in heart failure (HF), we hypothesized that SgII could play a role in cardiovascular pathophysiology. Methodology/Principal Findings: SgII production was characterized in a post-myocardial infarction heart failure (HF) mouse model, functional properties explored in experimental models, and circulating levels measured in mice and patients with stable HF of moderate severity. SgII mRNA levels were 10.5 fold upregulated in the left ventricle (LV) of animals with myocardial infarction and HF (p<0.001 vs. sham-operated animals). SgII protein levels were also increased in the LV, but not in other organs investigated. SgII was produced in several cell types in the myocardium and cardiomyocyte synthesis of SgII was potently induced by transforming growth factor-beta and norepinephrine stimulation in vitro. Processing of SgII to shorter peptides was enhanced in the failing myocardium due to increased levels of the proteases PC1/3 and PC2 and circulating SgII levels were increased in mice with HF. Examining a pathophysiological role of SgII in the initial phase of post-infarction HF, the SgII fragment secretoneurin reduced myocardial ischemia-reperfusion injury and cardiomyocyte apoptosis by 30% and rapidly increased cardiomyocyte Erk1/2 and Stat3 phosphorylation. SgII levels were also higher in patients with stable, chronic HF compared to age-and gender-matched control subjects: median 0.16 (Q1-3 0.14-0.18) vs. 0.12 (0.10-0.14) nmol/L, p<0.001. Conclusions: We demonstrate increased myocardial SgII production and processing in the LV in animals with myocardial infarction and HF, which could be beneficial as the SgII fragment secretoneurin protects from ischemia-reperfusion injury and cardiomyocyte apoptosis. Circulating SgII levels are also increased in patients with chronic, stable HF and may represent a new cardiac biomarker.
|
|
| 10. |
- Tandstad, Torgrim, et al.
(författare)
-
Management of Seminomatous Testicular Cancer : A Binational Prospective Population-Based Study From the Swedish Norwegian Testicular Cancer Study Group
- 2011
-
Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 29:6, s. 719-725
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: A binational, population-based treatment protocol was established to prospectively treat and follow patients with seminomatous testicular cancer. The aim was to standardize care for all patients with seminoma to further improve the good results expected for this disease. Patients and Methods From 2000 to 2006, a total of 1,384 Norwegian and Swedish patients were included in the study. Treatment in clinical stage 1 (CS1) was surveillance, adjuvant radiotherapy, or adjuvant carboplatin. In metastatic disease, recommended treatment was radiotherapy in CS2A and cisplatin-based chemotherapy in CS2B or higher. Results At a median follow-up of 5.2 years, 5-year cause-specific survival was 99.6%. In CS1, 14.3% (65 of 512) of patients relapsed following surveillance, 3.9% (seven of 188) after carboplatin, and 0.8% (four of 481) after radiotherapy. We could not identify any factors predicting relapse in CS1 patients who were subjected to surveillance only. In CS2A, 10.9% (three of 29) patients relapsed after radiotherapy compared with no relapses in CS2A/B patients (zero of 73) treated with chemotherapy (P = .011). Conclusion An international, population-based treatment protocol for testicular seminoma is feasible with excellent results. Surveillance remains a good option for CS1 patients. No factors predicted relapse in CS1 patients on surveillance. Despite resulting in a lower rate of relapse than with adjuvant carboplatin, adjuvant radiotherapy has been abandoned in the Swedish and Norwegian Testicular Cancer Project (SWENOTECA) as a recommended treatment option because of concerns of induction of secondary cancers. The higher number of relapses in radiotherapy-treated CS2A patients when compared with chemotherapy-treated CS2A/B patients is of concern. Late toxicity of cisplatin-based chemotherapy versus radiotherapy must be considered in CS2A patients.
|
|
