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  • 1.
    El Ouali, Mourad
    et al.
    University of Kiel, Germany.
    Fohlin, Helena
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Srivastav, Anand
    University of Kiel, Germany.
    A randomised approximation algorithm for the hitting set problem2014Inngår i: Theoretical Computer Science, ISSN 0304-3975, E-ISSN 1879-2294, Vol. 555, s. 23-34Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Let H = (V, epsilon) be a hypergraph with vertex set V and edge set epsilon, where n := vertical bar V vertical bar and m := vertical bar epsilon vertical bar. Let l be the maximum size of an edge and Delta be the maximum vertex degree. A hitting set (or vertex cover) in H is a subset of V in which all edges are incident. The hitting set problem is to find a hitting set of minimum cardinality. It is known that an approximation ratio of l can be achieved easily. On the other hand, for constant l, an approximation ratio better than l cannot be achieved in polynomial time under the unique games conjecture (Khot and Regev, 2008 [17]). Thus breaking the l-barrier for significant classes of hypergraphs is a complexity-theoretically and algorithmically interesting problem, which has been studied by several authors (Krivelevich, 1997 [18], Halperin, 2000 [12], Okun, 2005 [23]). We propose a randomised algorithm of hybrid type for the hitting set problem, which combines LP-based randomised rounding, graphs sparsening and greedy repairing and analyse it for different classes of hypergraphs. For hypergraphs with Delta = O(n1/4) and l = O (root n) we achieve an approximation ratio of l(1 - c/Delta), for some constant c greater than 0, with constant probability. For the case of hypergraphs where l and Delta are constants, we prove a ratio of l(1 - l-1/8 Delta). The latter is done by analysing the expected size of the hitting set and using concentration inequalities. Moreover, for quasi-regularisable hypergraphs, we achieve an approximation ratio of l(1 - n/8m). We show how and when our results improve over the results of Krivelevich, Halperin and Okun.

  • 2.
    Eriksson, Hanna
    et al.
    Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
    Lyth, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i västra Östergötland, Forsknings- och utvecklingsenheten för Närsjukvården i Östergötland. Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Månsson-Brahme, Eva
    Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
    Frohm-Nilsson, Margareta
    Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
    Ingvar, Christian
    Lund University, Sweden.
    Lindholm, Christer
    Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Naredi, Peter
    Sahlgrenska Academy, Gothenburg, Sweden.
    Stierner, Ulrika
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Carstensen, John
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälsa och samhälle. Linköpings universitet, Filosofiska fakulteten.
    Hansson, Johan
    Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
    Later stage at diagnosis and worse survival in cutaneous malignant melanoma among men living alone: a nationwide population-based study from Sweden2014Inngår i: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 32, nr 13, s. 1356-1364Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    PURPOSE:

    To investigate the association between cohabitation status, clinical stage at diagnosis, and disease-specific survival in cutaneous malignant melanoma (CMM).

    METHODS:

    This nationwide population-based study included 27,235 patients from the Swedish Melanoma Register diagnosed with a primary invasive CMM between 1990 and 2007 and linked data to nationwide, population-based registers followed up through 2012.

    RESULTS:

    After adjustment for age at diagnosis, level of education, living area, period of diagnosis, and tumor site, the odds ratios (ORs) of higher stage at diagnosis were significantly increased among men living alone versus men living with a partner (stage II v stage I: OR, 1.42; 95% CI, 1.29 to 1.57; stage III or IV v stage I: OR, 1.43; 95% CI, 1.14 to 1.79). The OR for stage II versus stage I disease was also increased among women living alone (OR, 1.15; 95% CI, 1.04 to 1.28). After adjustments for the factors listed earlier, the CMM-specific survival was significantly decreased among men living alone (hazard ratio [HR] for death, 1.48; 95% CI, 1.33 to 1.65; P < .001). After additional adjustments for all potential and established prognostic factors, CMM-specific survival among men living alone versus men living with a partner remained significantly decreased (HR, 1.31; 95% CI, 1.18 to 1.46; P < .001), suggesting a residual adverse effect on survival not accounted for by these parameters.

    CONCLUSION:

    In all age groups among men, living alone is significantly associated with reduced CMM-specific survival, partially attributed to a more advanced stage at diagnosis. This emphasizes the need for improved prevention and early detection strategies for this group.

  • 3.
    Eriksson, Hanna
    et al.
    Karolinska Institutet, Stockholm, Sweden.
    Lyth, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Månsson-Brahme, Eva
    Karolinska Institutet, Stockholm, Sweden.
    Frohm-Nilsson, Margareta
    Karolinska Institutet, Stockholm, Sweden.
    Ingvar, Christian
    Lund University, Sweden .
    Lindholm, Christer
    Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Naredi, Peter
    Umeå University, Sweden .
    Stierner, Ulrika
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Wagenius, Gunnar
    Uppsala University, Sweden .
    Carstensen, John
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälsa och samhälle. Linköpings universitet, Hälsouniversitetet.
    Hansson, Johan
    Karolinska Institutet, Stockholm, Sweden.
    Low level of education is associated with later stage at diagnosis and reduced survival in cutaneous malignant melanoma: A nationwide population-based study in Sweden2013Inngår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 49, nr 12, s. 2705-2716Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    A worse outcome has been reported for cutaneous malignant melanoma (CMM) patients with low socioeconomic status. We have investigated the association between level of education, clinical stage at diagnosis (stage at diagnosis) and CMM-specific survival in Sweden.

    METHODS:

    We identified 27,235 patients from the Swedish Melanoma Register diagnosed with a primary invasive CMM between 1990 and 2007 and linked data to nationwide, population-based, health and census registers with a follow-up to 2010.

    RESULTS:

    The odds ratio (OR) of higher disease stage at diagnosis was significantly increased in lower education groups (OR stage II versus I=1.6; 95% confidence interval (CI)=1.5-1.7. OR stage III-IV versus I=2.3; 95% CI=1.8-2.9). The risk of dying of CMM, was significantly increased in patients with low (hazard ratio (HR) low versus high=2.02; 95% CI=1.80-2.26; p<0.0001) and intermediate (HR intermediate versus high=1.35; 95% CI=1.20-1.51; p<0.0001) level of education. After adjustment for age, gender, stage at diagnosis and other known prognostic factors, the HRs remained significant for low versus high (HR=1.13; 95% CI=1.01-1.27; p=0.04) but not for intermediate versus high (HR=1.11; 95% CI=0.99-1.24; p=0.08) education. The HR associated with low level of education was significantly higher among female patients, patients <55years, patients with truncal tumours and during the first 5years after diagnosis.

    CONCLUSION:

    Lower level of education is associated with reduced CMM-specific survival, which may at least partially be attributed to a more advanced stage at diagnosis. These results emphasise the need for improved early detection strategies.

  • 4.
    Fohlin, Helena
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Perez-Tenorio, Gizeh
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet.
    Fornander, Tommy
    Karolinska University Hospital, Sweden.
    Skoog, Lambert
    Karolinska University Hospital, Sweden.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Carstensen, John
    Linköpings universitet, Institutionen för medicin och hälsa, Hälsa och samhälle. Linköpings universitet, Hälsouniversitetet.
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Akt2 expression is associated with good long-term prognosis in oestrogen receptor positive breast cancer2013Inngår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 49, nr 6, s. 1196-1204Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction

    Akt is a signalling modulator for many cellular processes, including metabolism, cell proliferation, cell survival and cell growth. Three isoforms of Akt have been identified, but only a few studies have concerned the isoform-specific roles in the prognosis of breast cancer patients. The aim of this study was to investigate the prognostic value of v-akt murine thymoma viral oncogene homologue 1 (Akt1) and v-akt murine thymoma viral oncogene homologue 2 (Akt2) in oestrogen receptor positive (ER+) and oestrogen receptor negative (ER–) breast cancer with long-term follow-up.

    Material and methods

    The expression of Akt in tumour tissue was analysed with immunohistochemistry in a cohort of 272 postmenopausal patients with stage II breast cancer. The median follow-up time was 19 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox’s proportional hazards model.

    Results

    The risk of distant recurrence was reduced for patients with ER+ tumours expressing Akt2 compared to patients with no Akt2 expression (HR = 0.49, 95% CI 0.29–0.82, p = 0.007). When adjusting for important clinical tumour characteristics and treatment, Akt2 was still an independent prognostic factor (HR = 0.38, 95% CI 0.21–0.68, p = 0.001) and the association remained long-term. The prognostic value of Akt2 increased with higher oestrogen receptor levels from no effect among patients with ER– tumours to 68% risk reduction for the group with high ER-levels (P for trend = 0.042). Akt1 showed no significant prognostic information.

    Conclusion

    Our results indicate that Akt2 expression is associated with a lower distant recurrence rate for patients with ER+ tumours and that this association remains long-term. The prognostic value of Akt2 increases with higher oestrogen receptor expression, motivating further mechanistic studies on the role of Akt2 in ER+ breast cancer.

    Fulltekst (pdf)
    fulltext
  • 5.
    Frödin, Ulla
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Omvårdnad. Linköpings universitet, Hälsouniversitetet.
    Lotfi, Kourosh
    Linköpings universitet, Institutionen för medicin och hälsa, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk farmakologi.
    Fomichov, Victoria
    Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Juliusson, Gunnar
    Department of Hematology and Coagulation, Skåne County Council, Stem Cell Center, Lund University, Lund, Sweden.
    Börjeson, Sussanne
    Linköpings universitet, Institutionen för medicin och hälsa, Omvårdnad. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Early and Long-Term Follow-Up of Health-Related Quality of Life Following Allogeneic Hematopoietic Stem-Cell Transplantation2013Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Health-related quality of life (HRQL) of 94 consecutive patients undergoing allogeneic stem cell transplantation (SCT) with myeloablative conditioning (MAC, n = 18) or reduced intensity conditioning (RIC, n = 76) was evaluated using the EORTC QLQ C-30 questionnaire at baseline and 12 times up to 3 years after SCT. Functional status and the global quality of life decreased from baseline to weeks 2 and 3, especially role and social functions. Symptoms increased significantly during the first three weeks, particularly appetite loss, nausea and vomiting, diarrhea, and fatigue. It took at least one year for HRQL to return to the baseline level. The only function that improved significantly three years after SCT was role function. MAC patients experienced worse HRQL at baseline than RIC patients, and subsequently more pain, sleep disturbance, and appetite loss in weeks 3 and 4. Patients with extensive chronic graft-versus-host disease (GvHD) experienced reduced HRQL. These results provide a good overview of patients’ symptoms and HRQL during and after SCT and indicate when they require increased support. The results also demonstrate the importance of close follow-ups during the first year after SCT in order to improve the preventive interventions, particularly regarding appetite loss and chronic GvHD.

  • 6.
    Jancke, Georg
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Rosell, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Chebil, Gunilla
    County Hospital, Helsingborg, Sweden.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Bladder Wash Cytology at Diagnosis of Ta-T1 Bladder Cancer Is Predictive for Recurrence and Progression2012Inngår i: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 80, nr 3, s. 625-631Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE To evaluate the effect of the bladder wash cytology finding at the primary diagnosis of Stage Ta-T1 urinary bladder cancer on recurrence and progression. less thanbrgreater than less thanbrgreater thanMETHODS The clinical and pathologic characteristics of all patients with primary Stage Ta-T1 urinary bladder cancer were prospectively registered. The data were divided according to the bladder wash cytology results at diagnosis. Multivariate analyses were performed to determine the influence of bladder wash cytology on recurrence and progression. less thanbrgreater than less thanbrgreater thanRESULTS The analysis included 768 evaluable patients with a mean follow-up of 60 months. Recurrence was observed in 478 patients (62%) and progression in 71 (9%). High-grade malignant bladder wash cytology was predictive for recurrence and progression (P andlt; .001 and P = .036, respectively). Other factors affecting recurrence were missing bladder wash cytology data, tumors size 16-30 mm and andgt;30 mm, Stage T1 tumor category, and multiplicity (P = .008, P = .006, P andlt; .001, P = .002, and P andlt; .001, respectively). Progression was also associated with T1 tumor category, local recurrence, and primary concomitant carcinoma in situ (P andlt; .001, P andlt; .001, and P = .024, respectively). less thanbrgreater than less thanbrgreater thanCONCLUSION High-grade malignant bladder wash cytology at the primary diagnosis was predictive for recurrence and progression. This could be taken into account in designing future follow-up schedules.

  • 7.
    Jancke, Georg
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Rosell, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Impact of surgical experience on recurrence and progression after transurethral resection of bladder tumour in non-muscle-invasive bladder cancer2014Inngår i: SCANDINAVIAN JOURNAL OF UROLOGY, ISSN 2168-1805, Vol. 48, nr 3, s. 276-283Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: To evaluate the impact of experience in transurethral resection of bladder tumor (TUR-BT) on recurrence and progression in primary Ta/T1 urinary bladder cancer.

    Methods: Clinical and pathological characteristics of patients with primary Ta/T1 urinary bladder cancer were recorded prospectively from 1992 to 2007 inclusive. Data on surgeons’ experience were categorized as follows: (a) experience by training status (residents or specialists); (b) number of TUR-BTs performed by each surgeon during the registration period, with cut-off levels at > 100, > 150, > 200, > median, and > third quartile of surgical volume; (c) lifetime high-volume surgeons (> 100 TUR-BTs). Hazard ratios (HRs) were estimated using Cox regression with 95% confidence intervals (CIs) in both univariate and multivariate analysis.

    Results: The analysis included 768 evaluable patients with a median follow-up of 60 months. Recurrence was observed in 478 patients (62%) and progression in 71 (9%). Surgery was performed by residents in 100 cases and specialists in 668, with recurrence in 75 (75%) and 403 (60%) patients, and progression in 9 (9%) and 62 (9%), respectively. Surgery performed by residents was statistically associated with recurrence (HR = 0.69, 95% CI = 0.54-0.89) but not progression (HR = 0.72, 95% CI = 0.35-1.48). Surgical volume (b and c) was not found to have a significant impact on recurrence or progression in any of the analyses at the chosen cut-offs.

    Conclusions: Surgical experience (specialist/resident) was a predictive factor for recurrence after TUR-BT for Ta/T1 bladder cancer. However, surgeon volume was not associated with recurrence at the chosen cut-off levels. Training programs, checklist

  • 8.
    Jancke, Georg
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Rosell, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Residual tumour in the marginal resection after a complete transurethral resection is associated with local recurrence in Ta/T1 urinary bladder cancer2012Inngår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 46, nr 5, s. 343-347Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective. This study investigated the presence of residual tumour in the marginal resection (MR) after a complete transurethral resection (TURB) of Ta/T1 transitional urinary bladder cancer. The association between positive MR and recurrence was analysed. Material and methods. After macroscopically complete TURB, a marginal resection of 7 mm (corresponding to the diameter of the resection loop) was removed around the entire resection area. Univariate and multivariate Cox regression analyses were performed to assess the influence of residual disease on recurrence. Results. In all, 94 patients with a median follow-up time of 36 months were included, and residual tumour in the MR was present in 24 (26%). The recurrence rates for all cases, for those with a tumour-positive and a tumour-free MR were 60 (64%), 20 (83%) and 40 (57%), respectively. Local recurrence was found in 14 (58%) of the patients with tumour presence in the MR compared to 13 (19%) of those with a tumour-free margin. A positive MR was significantly associated with overall recurrence (p andlt; 0.001) and local recurrence (p = 0.001). Conclusion. Incomplete transurethral resection of bladder cancer is common, as demonstrated in 26% patients with positive MR. The presence of tumour in the MR may be a risk factor for recurrence, and particularly local recurrence.

  • 9.
    Loorents, Vera
    et al.
    Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Rosell, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Karlsson, Charlott
    Ryhov County Hospital, Jönköping, Sweden.
    Lidback, Maria
    Ryhov County Hospital, Jönköping, Sweden.
    Hultman, Kristina
    Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Börjeson, Sussanne
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Prophylactic training for the prevention of radiotherapy-induced trismus - a randomised study2014Inngår i: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, nr 4, s. 530-538Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND:

    Radiotherapy-induced trismus (RTIT) is a debilitating condition without any proven effective treatment. This study investigates the effectiveness of prophylactic training to prevent RTIT during and up to 12 months after completed RT in patients with head and neck cancer (HNC), also investigating the incidence of RTIT.

    METHODS:

    Sixty-six consecutive patients from two RT clinics in Sweden were randomised into one of two groups: training with TheraBite(®) Jaw Motion Rehabilitation System(™) or a control group. Maximum interincisal openings (MIO) were recorded at baseline and once a week during treatment, three, six and 12 months after completed RT. Training frequency was recorded by patients in a log book.

    RESULTS:

    There were no significant differences in MIO between the intervention and control groups at any of the measurement points. Patients in both groups maintained their normal variation in MIO at 12 months after completed RT. A small group of patients in the control group had a 17% mean decrease in MIO by week 6 compared to baseline and improved their MIO by using the training programme. There was a significant mean difference in MIO from baseline to week 6 (3 mm, p = 0.018), and month 6 (2.7 mm, p = 0.040), for patients receiving 3D conformal radiotherapy. There was a significant difference in MIO between patients treated with RT and concurrent chemotherapy compared to patients with RT only at 12 months (p = 0.033).

    CONCLUSIONS:

    Patients with HNC undergoing high dose RT do not need to be burdened with an intense prophylactic training programme during RT and up to 12 months after completed RT. MIO measurements during RT and up to 12 months after completed RT are recommended to identify a small risk group who are an exception and may need a training programme.

    Fulltekst (pdf)
    fulltext
  • 10. Bestill onlineKjøp publikasjonen >>
    Lyth, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Clinical-epidemiological studies on cutaneous malignant melanoma: A register approach2015Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The incidence of cutaneous malignant melanoma (CMM) is steadily increasing. Most of the patients have thin CMM with a good prognosis and a 5-year survival of about 90%. The prognosis is highly related to tumour thickness and clinical stage at diagnosis. Effective systemic treatment for patients with metastatic disease has only recently been available. This thesis aims to increase knowledge of trends in tumour thickness, prognostic factors, socioeconomic differences and medical costs in patients with CMM.

    The population-based Swedish melanoma register is the main source of data in all papers in the thesis. Papers I-III include patients from all of Sweden while paper IV is delimited to the County of Östergötland. Cox regression and logistic regression are the main multivariable methods used. Paper IV is focused on stage-specific costs of CMM by comparing direct healthcare costs to a general population.

    For men, there has been a shift over time towards thinner tumours at diagnosis accompanied by an improved survival. Women are still diagnosed with considerably thinner tumours and they experience a better survival than men. Tumour ulceration, tumour thickness and Clark’s level of invasion all showed significant independent long-term prognostic information in T1 CMMs. By combining these factors, three distinct prognostic subgroups were identified. Lower level of education was associated with reduced CMM-specific survival, which may at least partially be attributed to a more advanced stage at diagnosis. The direct healthcare costs for CMM patients were significantly higher than for the general population, independent of clinical stage. CMM patients diagnosed in clinical stage III-IV were associated with particularly high costs.

    Even though the survival among Swedish patients with CMM is among the highest in the world and still seems to improve, the results of this thesis emphasise the need of improved early detection strategies. This may be of particular concern in men, older women, and groups with a low level of education. The results also imply that the costs for the management of CMM patients may be reduced if early detection efforts are successful and lead to a more favourable stage distribution. The finding of a better risk stratification of thin CMMs may help to improve the management of this large patient group.

    Delarbeid
    1. Trends in cutaneous malignant melanoma in Sweden 1997-2011: Thinner tumours and improved survival among men
    Åpne denne publikasjonen i ny fane eller vindu >>Trends in cutaneous malignant melanoma in Sweden 1997-2011: Thinner tumours and improved survival among men
    Vise andre…
    2015 (engelsk)Inngår i: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 172, nr 3, s. 700-706Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background: Both patient survival and the proportion of patients diagnosed with thin cutaneous malignant melanoma (CMM) have been steadily rising in Sweden as in most western countries, though the rate of improvement in survival appears to have declined in Sweden at the end of last millennium.

    Objectives: To analyse the most recent trends in the distribution of tumour thickness (T-category) as well as CMM-specific survival in Swedish patients diagnosed 1997-2011.

    Methods: This nationwide population-based study included 30 590 patients registered in the Swedish Melanoma Register (SMR) and diagnosed with a first primary invasive CMM 1997-2011. The patients were followed through 2012 in the national Cause-of-Death Register.

    Results: Logistic and Cox regression analyses adjusting for age at diagnosis, tumour site, and health care region were carried out. The odds ratio for being diagnosed with thicker tumours was significantly reduced (P = 0·0008) and the CMM-specific survival significantly improved in men diagnosed 2007-2011 compared to men diagnosed 1997-2001 (hazard ratio=0·81; 95% CI 0·72-0·91, P = 0·0009) while the corresponding differences for women were not significant. Women were diagnosed with significantly thicker tumours during 2002-2006 and a tendency towards decreased survival was observed compared to those diagnosed earlier 1997-2001 and later 2007-2011.

    Conclusion: In Sweden, the CMMs of men are detected earlier over time and this seems to be followed by an improved CMM-specific survival for men. Women are still diagnosed with considerably thinner tumours and they experience a better survival than men.

    sted, utgiver, år, opplag, sider
    Wiley-Blackwell, 2015
    Emneord
    malignant melanoma, time trend, survival, tumour thickness, population based
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-113143 (URN)10.1111/bjd.13483 (DOI)000351400500029 ()25323770 (PubMedID)
    Tilgjengelig fra: 2015-01-12 Laget: 2015-01-12 Sist oppdatert: 2017-12-05bibliografisk kontrollert
    2. Prognostic subclassifications of T1 cutaneous melanomas based on ulceration, tumour thickness and Clark’s level of invasion: results of a population-based study from the Swedish Melanoma Register
    Åpne denne publikasjonen i ny fane eller vindu >>Prognostic subclassifications of T1 cutaneous melanomas based on ulceration, tumour thickness and Clark’s level of invasion: results of a population-based study from the Swedish Melanoma Register
    Vise andre…
    2013 (engelsk)Inngår i: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 168, nr 4, s. 779-786Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background  Survival and prognostic factors for thin melanomas have been studied relatively little in population-based settings. This patient group accounts for the majority of melanomas diagnosed in western countries today, and better prognostic information is needed.

    Objectives  The aim of this study was to use established prognostic factors such as ulceration, tumour thickness and Clark’s level of invasion for risk stratification of T1 cutaneous melanoma.

    Methods  From 1990 to 2008, the Swedish Melanoma Register included 97% of all melanomas diagnosed in Sweden. Altogether, 13 026 patients with T1 melanomas in clinical stage I were used for estimating melanoma-specific 10- and 15-year mortality rates. The Cox regression model was used for further survival analysis on 11 165 patients with complete data.

    Results  Ulceration, tumour thickness and Clark’s level of invasion all showed significant, independent, long-term prognostic information. By combining these factors the patients could be subdivided into three risk groups: a low-risk group (67·9% of T1 cases) with a 10-year melanoma-specific mortality rate of 1·5% (1·2–1·9%); an intermediate-risk group (28·6% of T1 cases) with a 10-year mortality rate of 6·1% (5·0–7·3%); and a high-risk group (3·5% of T1 cases) with a 10-year mortality rate of 15·6% (11·2–21·4%). The high- and intermediate-risk groups accounted for 66% of melanoma deaths within T1.

    Conclusions  Using a population-based melanoma register, and combining ulceration, tumour thickness and Clark’s level of invasion, three distinct prognostic subgroups were identified.

    sted, utgiver, år, opplag, sider
    Wiley-Blackwell, 2013
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-92611 (URN)10.1111/bjd.12095 (DOI)000317016100030 ()23066913 (PubMedID)
    Merknad

    Funding Agencies|regional cancer centre Southeast in Linkoping||

    Tilgjengelig fra: 2013-05-16 Laget: 2013-05-14 Sist oppdatert: 2017-12-06
    3. Low level of education is associated with later stage at diagnosis and reduced survival in cutaneous malignant melanoma: A nationwide population-based study in Sweden
    Åpne denne publikasjonen i ny fane eller vindu >>Low level of education is associated with later stage at diagnosis and reduced survival in cutaneous malignant melanoma: A nationwide population-based study in Sweden
    Vise andre…
    2013 (engelsk)Inngår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 49, nr 12, s. 2705-2716Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    BACKGROUND:

    A worse outcome has been reported for cutaneous malignant melanoma (CMM) patients with low socioeconomic status. We have investigated the association between level of education, clinical stage at diagnosis (stage at diagnosis) and CMM-specific survival in Sweden.

    METHODS:

    We identified 27,235 patients from the Swedish Melanoma Register diagnosed with a primary invasive CMM between 1990 and 2007 and linked data to nationwide, population-based, health and census registers with a follow-up to 2010.

    RESULTS:

    The odds ratio (OR) of higher disease stage at diagnosis was significantly increased in lower education groups (OR stage II versus I=1.6; 95% confidence interval (CI)=1.5-1.7. OR stage III-IV versus I=2.3; 95% CI=1.8-2.9). The risk of dying of CMM, was significantly increased in patients with low (hazard ratio (HR) low versus high=2.02; 95% CI=1.80-2.26; p<0.0001) and intermediate (HR intermediate versus high=1.35; 95% CI=1.20-1.51; p<0.0001) level of education. After adjustment for age, gender, stage at diagnosis and other known prognostic factors, the HRs remained significant for low versus high (HR=1.13; 95% CI=1.01-1.27; p=0.04) but not for intermediate versus high (HR=1.11; 95% CI=0.99-1.24; p=0.08) education. The HR associated with low level of education was significantly higher among female patients, patients <55years, patients with truncal tumours and during the first 5years after diagnosis.

    CONCLUSION:

    Lower level of education is associated with reduced CMM-specific survival, which may at least partially be attributed to a more advanced stage at diagnosis. These results emphasise the need for improved early detection strategies.

    sted, utgiver, år, opplag, sider
    Elsevier, 2013
    Emneord
    Melanoma, Survival, Socioeconomic status, Level of education, Stage at diagnosis, Population-based
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-95938 (URN)10.1016/j.ejca.2013.03.013 (DOI)000321336800010 ()23583439 (PubMedID)
    Merknad

    Funding Agencies|Swedish Cancer Society||Radiumhemmet Research Funds||Sigurd and Elsa Goljes Memorial Foundation||Stockholm County Council||

    Tilgjengelig fra: 2013-08-19 Laget: 2013-08-12 Sist oppdatert: 2017-12-06bibliografisk kontrollert
    4. Stage-specific direct healthcare costs in patients with cutaneous malignant melanoma
    Åpne denne publikasjonen i ny fane eller vindu >>Stage-specific direct healthcare costs in patients with cutaneous malignant melanoma
    2016 (engelsk)Inngår i: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 30, nr 5, s. 789-793Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background Clinical stage at diagnosis is a strong prognostic factor for death in cutaneous malignant melanoma (CMM), with worse prognosis at higher stages. However, few studies have investigated how direct healthcare cost per patient varies with clinical stage.

    Objective The aim of this study was to determine the stage-specific direct healthcare costs for CMM patients compared to the healthcare costs in the general population in the County of Östergötland, Sweden.

    Methods CMM patients in the County of Östergötland diagnosed 2005-2012 were identified from the Swedish cancer registry. Information on clinical stage was collected from the Swedish Melanoma Register (SMR) and cost data from the Cost per Patient database (CPP) for 1 075 CMM patients in Östergötland. CPP contains costs associated with all healthcare contacts per patient including inpatient, outpatient, and primary care. The CMM-related costs were defined as the difference in mean healthcare costs between CMM patients and general population.

    Results The first year after CMM diagnosis, the average healthcare costs for CMM patients was 2.8 times higher than in the general population. The healthcare cost ratio varied from 2.0 (stage I) to 10.1 (stage IV) and the CMM-related costs per patient-year varied from €2 670 (stage I) to €29 291 (stage IV). The mean healthcare costs decreased over time but remained significantly higher than in the general population for all clinical stages. During the first year after diagnosis, patients in clinical stage III-IV (7% of CMM patients) accounted for 27% of the total CMM-related healthcare costs.

    Conclusions The direct healthcare costs for CMM patients were significantly higher than in the general population independent of clinical stage. CMM patients diagnosed in clinical stage III-IV were associated with particularly high costs and the healthcare system may save resources by finding CMM patients in earlier stages.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-113144 (URN)10.1111/jdv.13110 (DOI)000374554200007 ()
    Merknad

    Funding agencies:Regional cancer center South East in Linkoping

    Vid tiden för disputation förelåg publikationen som manuskript

    Tilgjengelig fra: 2015-01-12 Laget: 2015-01-12 Sist oppdatert: 2017-05-03
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  • 11.
    Lyth, Johan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum. Linköpings universitet, Medicinska fakulteten.
    Carstensen, John
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Medicinska fakulteten.
    Synnerstad, Ingrid
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Hudkliniken i Östergötland. Linköpings universitet, Medicinska fakulteten.
    Lindholm, Christer
    Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Stage-specific direct healthcare costs in patients with cutaneous malignant melanoma2016Inngår i: Journal of the European Academy of Dermatology and Venereology, ISSN 0926-9959, E-ISSN 1468-3083, Vol. 30, nr 5, s. 789-793Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Clinical stage at diagnosis is a strong prognostic factor for death in cutaneous malignant melanoma (CMM), with worse prognosis at higher stages. However, few studies have investigated how direct healthcare cost per patient varies with clinical stage.

    Objective The aim of this study was to determine the stage-specific direct healthcare costs for CMM patients compared to the healthcare costs in the general population in the County of Östergötland, Sweden.

    Methods CMM patients in the County of Östergötland diagnosed 2005-2012 were identified from the Swedish cancer registry. Information on clinical stage was collected from the Swedish Melanoma Register (SMR) and cost data from the Cost per Patient database (CPP) for 1 075 CMM patients in Östergötland. CPP contains costs associated with all healthcare contacts per patient including inpatient, outpatient, and primary care. The CMM-related costs were defined as the difference in mean healthcare costs between CMM patients and general population.

    Results The first year after CMM diagnosis, the average healthcare costs for CMM patients was 2.8 times higher than in the general population. The healthcare cost ratio varied from 2.0 (stage I) to 10.1 (stage IV) and the CMM-related costs per patient-year varied from €2 670 (stage I) to €29 291 (stage IV). The mean healthcare costs decreased over time but remained significantly higher than in the general population for all clinical stages. During the first year after diagnosis, patients in clinical stage III-IV (7% of CMM patients) accounted for 27% of the total CMM-related healthcare costs.

    Conclusions The direct healthcare costs for CMM patients were significantly higher than in the general population independent of clinical stage. CMM patients diagnosed in clinical stage III-IV were associated with particularly high costs and the healthcare system may save resources by finding CMM patients in earlier stages.

  • 12.
    Lyth, Johan
    et al.
    Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Eriksson, H.
    Department of Oncology-Pathology, Karolinska Institute, Stockholm.
    Hansson, J.
    Department of Oncology-Pathology, Karolinska Institute, Stockholm.
    Ingvar, C.
    Department of Surgery, Lund University Hospital, Lund.
    Jansson, M.
    Department of Surgery, Umeå University, Umeå.
    Lapins, J.
    Department of Dermatology, Karolinska University Hospital, Stockholm.
    Månsson-Brahme, E.
    Department of Oncology-Pathology, Karolinska Institute, Stockholm.
    Naredi, P.
    Department of Surgery, University of Gothenburg, Sahlgrenska University Hospital, Göteborg.
    Stierner, U.
    Department of Oncology, Sahlgrenska University Hospital, Göteborg.
    Ullenhag, G.
    Department of Radiology, Oncology and Radiation Science, Section of Oncology, Uppsala University, Uppsala.
    Carstensen, John
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Medicinska fakulteten.
    Lindholm, C.
    Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Trends in cutaneous malignant melanoma in Sweden 1997-2011: Thinner tumours and improved survival among men2015Inngår i: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 172, nr 3, s. 700-706Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Both patient survival and the proportion of patients diagnosed with thin cutaneous malignant melanoma (CMM) have been steadily rising in Sweden as in most western countries, though the rate of improvement in survival appears to have declined in Sweden at the end of last millennium.

    Objectives: To analyse the most recent trends in the distribution of tumour thickness (T-category) as well as CMM-specific survival in Swedish patients diagnosed 1997-2011.

    Methods: This nationwide population-based study included 30 590 patients registered in the Swedish Melanoma Register (SMR) and diagnosed with a first primary invasive CMM 1997-2011. The patients were followed through 2012 in the national Cause-of-Death Register.

    Results: Logistic and Cox regression analyses adjusting for age at diagnosis, tumour site, and health care region were carried out. The odds ratio for being diagnosed with thicker tumours was significantly reduced (P = 0·0008) and the CMM-specific survival significantly improved in men diagnosed 2007-2011 compared to men diagnosed 1997-2001 (hazard ratio=0·81; 95% CI 0·72-0·91, P = 0·0009) while the corresponding differences for women were not significant. Women were diagnosed with significantly thicker tumours during 2002-2006 and a tendency towards decreased survival was observed compared to those diagnosed earlier 1997-2001 and later 2007-2011.

    Conclusion: In Sweden, the CMMs of men are detected earlier over time and this seems to be followed by an improved CMM-specific survival for men. Women are still diagnosed with considerably thinner tumours and they experience a better survival than men.

    Fulltekst (pdf)
    fulltext
  • 13.
    Lyth, Johan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Hansson, J.
    Department of Oncology–Pathology, Karolinska Institute, Stockholm, Sweden.
    Ingvar, C.
    Department of Surgery, Lund University Hospital, Lund, Sweden.
    Mansson-Brahme, E.
    Department of Oncology–Pathology, Karolinska Institute, Stockholm, Sweden.
    Naredi, P.
    Department of Surgery, Umeå University, Umeå, Sweden.
    Stierner, U.
    Department of Oncology, Sahlgrenska University Hospital, Göteborg, Sweden.
    Wagenius, G.
    Department of Oncology, Akademiska University Hospital, Uppsala, Sweden.
    Lindholm, C.
    Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Prognostic subclassifications of T1 cutaneous melanomas based on ulceration, tumour thickness and Clark’s level of invasion: results of a population-based study from the Swedish Melanoma Register2013Inngår i: British Journal of Dermatology, ISSN 0007-0963, E-ISSN 1365-2133, Vol. 168, nr 4, s. 779-786Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background  Survival and prognostic factors for thin melanomas have been studied relatively little in population-based settings. This patient group accounts for the majority of melanomas diagnosed in western countries today, and better prognostic information is needed.

    Objectives  The aim of this study was to use established prognostic factors such as ulceration, tumour thickness and Clark’s level of invasion for risk stratification of T1 cutaneous melanoma.

    Methods  From 1990 to 2008, the Swedish Melanoma Register included 97% of all melanomas diagnosed in Sweden. Altogether, 13 026 patients with T1 melanomas in clinical stage I were used for estimating melanoma-specific 10- and 15-year mortality rates. The Cox regression model was used for further survival analysis on 11 165 patients with complete data.

    Results  Ulceration, tumour thickness and Clark’s level of invasion all showed significant, independent, long-term prognostic information. By combining these factors the patients could be subdivided into three risk groups: a low-risk group (67·9% of T1 cases) with a 10-year melanoma-specific mortality rate of 1·5% (1·2–1·9%); an intermediate-risk group (28·6% of T1 cases) with a 10-year mortality rate of 6·1% (5·0–7·3%); and a high-risk group (3·5% of T1 cases) with a 10-year mortality rate of 15·6% (11·2–21·4%). The high- and intermediate-risk groups accounted for 66% of melanoma deaths within T1.

    Conclusions  Using a population-based melanoma register, and combining ulceration, tumour thickness and Clark’s level of invasion, three distinct prognostic subgroups were identified.

    Fulltekst (pdf)
    fulltext
  • 14.
    Malmström, Annika
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, LAH Linköping.
    Henning Gronberg, Bjorn
    St Olav's Hospital, Trondheim University Hospital Norwegian University of Science and Technology, Trondheim, Norway.
    Marosi, Christine
    Medical University of Vienna, Austria .
    Stupp, Roger
    Lausanne University Hospital, Switzerland.
    Frappaz, Didier
    Centre Léon Bérard, Lyon, France.
    Schultz, Henrik
    Aarhus University Hospital, Denmark .
    Abacioglu, Ufuk
    Marmara University Hospital, Istanbul, Turkey.
    Tavelin, Bjorn
    Umeå University, Sweden .
    Lhermitte, Benoit
    Lausanne University Hospital, Switzerland .
    Hegi, Monika E
    Lausanne University Hospital, Switzerland .
    Rosell, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Henriksson, Roger
    Umeå University, Sweden Regional Cancer Centre Stockholm and Gotland, Sweden .
    Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial2012Inngår i: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 13, nr 9, s. 916-926Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Most patients with glioblastoma are older than 60 years, but treatment guidelines are based on trials in patients aged only up to 70 years. We did a randomised trial to assess the optimum palliative treatment in patients aged 60 years and older with glioblastoma. less thanbrgreater than less thanbrgreater thanMethods Patients with newly diagnosed glioblastoma were recruited from Austria, Denmark, France, Norway, Sweden, Switzerland, and Turkey. They were assigned by a computer-generated randomisation schedule, stratified by centre, to receive temozolomide (200 mg/m(2) on days 1-5 of every 28 days for up to six cycles), hypofractionated radiotherapy (34.0 Gy administered in 3.4 Gy fractions over 2 weeks), or standard radiotherapy (60.0 Gy administered in 2.0 Gy fractions over 6 weeks). Patients and study staff were aware of treatment assignment. The primary endpoint was overall survival. Analyses were done by intention to treat. This trial is registered, number ISRCTN81470623. less thanbrgreater than less thanbrgreater thanFindings 342 patients were enrolled, of whom 291 were randomised across three treatment groups (temozolomide n=93, hypofractionated radiotherapy n=98, standard radiotherapy n=100) and 51 of whom were randomised across only two groups (temozolomide n=26, hypofractionated radiotherapy n=25). In the three-group randomisation, in comparison with standard radiotherapy, median overall survival was significantly longer with temozolomide (8.3 months [95% CI 7.1-9.5; n=93] vs 6.0 months [95% CI 5.1-6.8; n=100], hazard ratio [HR] 0.70; 95% CI 0.52-0.93, p=0.01), but not with hypofractionated radiotherapy (7.5 months [6.5-8.6; n=98], HR 0.85 [0.64-1.12], p=0.24). For all patients who received temozolomide or hypofractionated radiotherapy (n=242) overall survival was similar (8.4 months [7.3-9.4; n=119] vs 7.4 months [6.4-8.4; n=123]; HR 0.82, 95% CI 0.63-1.06; p=0.12). For age older than 70 years, survival was better with temozolomide and with hypofractionated radiotherapy than with standard radiotherapy (HR for temozolomide vs standard radiotherapy 0.35 [0.21-0.56], pandlt;0.0001; HR for hypofractionated vs standard radiotherapy 0.59 [95% CI 0.37-0.93], p=0.02). Patients treated with temozolomide who had tumour MGMT promoter methylation had significantly longer survival than those without MGMT promoter methylation (9.7 months [95% CI 8.0-11.4] vs 6.8 months [5.9-7.7]; HR 0.56 [95% CI 0.34-0.93], p=0.02), but no difference was noted between those with methylated and unmethylated MGMT promoter treated with radiotherapy (HR 0.97 [95% CI 0.69-1.38]; p=0.81). As expected, the most common grade 3-4 adverse events in the temozolomide group were neutropenia (n=12) and thrombocytopenia (n=18). Grade 3-5 infections in all randomisation groups were reported in 18 patients. Two patients had fatal infections (one in the temozolomide group and one in the standard radiotherapy group) and one in the temozolomide group with grade 2 thrombocytopenia died from complications after surgery for a gastrointestinal bleed. less thanbrgreater than less thanbrgreater thanInterpretation Standard radiotherapy was associated with poor outcomes, especially in patients older than 70 years. Both temozolomide and hypofractionated radiotherapy should be considered as standard treatment options in elderly patients with glioblastoma. MGMT promoter methylation status might be a useful predictive marker for benefit from temozolomide.

  • 15.
    Malmström, Annika
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, LAH Linköping.
    Stupp, Roger
    Lausanne University Hospital, Switzerland.
    Hegi, Monika
    Lausanne University Hospital, Switzerland.
    Rosell, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Henriksson, Roger
    Umeå University, Sweden Regional Cancer Centre Stockholm and Gotland, Sweden .
    Treatment options in elderly patients with glioblastoma - Authors' reply2012Inngår i: The Lancet Oncology, ISSN 1470-2045, E-ISSN 1474-5488, Vol. 13, nr 11, s. E461-E462Artikkel i tidsskrift (Annet vitenskapelig)
  • 16.
    Olsson, Hans
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Hultman, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Monsef, Nastaran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Rosell, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Johanson, Staffan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Urologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Immunohistochemical Evaluation of Cell Cycle Regulators: Impact on Predicting Prognosis in Stage T1 Urinary Bladder Cancer2012Inngår i: ISRN Urology, ISSN 2090-5807, E-ISSN 2090-5815, Vol. 2012, artikkel-id 379081Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Background and Objective. The cell cycle is regulated by proteins at different checkpoints, and dysregulation of this cycle plays a role in carcinogenesis. Matrix metalloproteinases (MMPs) are enzymes that degrade collagen and promote tumour infiltration. The aim of this study was to evaluate the expression of various cell cycle regulators and MMPs, and to correlate such expression with progression and recurrence in patients with stage T1 urothelial carcinoma of the bladder (UCB).

    Patients and Methods. This population-based cohort study comprised 201 well-characterized patients with primary stage T1 urothelial carcinoma of the bladder. Immunohistochemistry was performed on formalin-fixed material to quantify expression of cell cycle regulators and two MMPs.

    Results. Normal expression of p53 and abnormal expression of MMP9 were associated with greater risk of tumour recurrence. Also, normal p16 expression was related to a lower risk of tumour progression. MMP2, p21, cyclin D1, and pRb showed no significant results that could estimate progression or recurrence.

    Conclusions. Normal p16 expression is associated with a lower risk of tumour progression, but immunohistochemistry on cell cycle regulators and MMPs has little value in predicting the prognosis in stage T1 UCB.

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    fulltext
  • 17.
    Olsson, Hans
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Hultman, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Rosell, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    Population-based study on prognostic factors for recurrence and progression in primary stage T1 bladder tumours2013Inngår i: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 47, nr 3, s. 188-195Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective. Stage T1 urothelial carcinoma of the bladder (UCB) exhibits heterogeneous clinical behaviour, and the treatment is controversial. The aim of this study was to evaluate prognostic factors for UCB in a defined, population-based cohort comprising patients with a first time diagnosis of primary stage T1 UCB.

    Material and methods. The study population initially consisted of 285 patients with primary stage T1 UCB reported to the regional Bladder Cancer Registry in the Southeast Healthcare Region of Sweden from 1992 to 2001. The histological specimens were re-evaluated concerning stage, substaging of T1, World Health Organization (WHO) grade, lymphovascular invasion (LVI), tumour volume and total resected volume. Hospital records provided data on tumour size and multiplicity, occurrence of possible relapse and/or progression, death from UCB and whether treatment was given.

    Results. After re-evaluation, the study population comprised 211 patients. The median follow-up time was 60 months. LVI was a prognostic factor for UCB progression and recurrence. Tumour size larger than 30 mm and multiplicity increased the risk of recurrence. T1 substaging, tumour volume and total resected volume were not associated with recurrence or tumour progression.

    Conclusions. LVI is significantly correlated with progression and recurrence in patients with primary stage T1 UCB. Therefore, the presence of LVI should be evaluated in every new case of T1 UCB.

  • 18.
    Olsson, Hans
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Hultman, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Molekylär och immunologisk patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Rosell, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Jahnson, Staffan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Urologiska kliniken i Östergötland.
    MDM2 SNP309 promoter polymorphism and p53 mutations in urinary bladder carcinoma stage T12013Inngår i: BMC Urology, ISSN 1471-2490, E-ISSN 1471-2490, Vol. 13, nr 5Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Urinary bladder carcinoma stage T1 is an unpredictable disease that in some cases has a good prognosis with only local or no recurrence, but in others can appear as a more aggressive tumor with progression to more advanced stages. The aim here was to investigate stage T1 tumors regarding MDM2 promoter SNP309 polymorphism, mutations in the p53 gene, and expression of p53 and p16 measured by immunohistochemistry, and subsequently relate these changes to tumor recurrence and progression. We examined a cohort of patients with primary stage T1 urothelial carcinoma of the bladder and their tumors.

    Methods: After re-evaluation of the original slides and exclusions, the study population comprised 141 patients, all with primary stage T1 urothelial carcinoma of the bladder. The hospital records were screened for clinical parameters and information concerning presence of histologically proven recurrence and progression. The paraffin-embedded tumor material was evaluated by immunohistochemistry. Any mutations found in the p53 gene were studied by single-strand conformation analysis and Sanger sequencing. The MDM2 SNP309 polymorphism was investigated by pyrosequencing. Multivariate analyses concerning association with prognosis were performed, and Kaplan-Meier analysis was conducted for a combination of changes and time to progression.

    Results: Of the 141 patients, 82 had at least one MDM2 SNP309 G allele, and 53 had a mutation in the p53 gene, but neither of those anomalies was associated with a worse prognosis. A mutation in the p53 gene was associated with immunohistochemically visualized p53 protein expression at a cut-off value of 50%. In the group with p53 mutation Kaplan-Meier analysis showed higher rate of progression and shorter time to progression in patients with immunohistochemically abnormal p16 expression compared to them with normal p16 expression (p = 0.038).

    Conclusions: MDM2 SNP309 promoter polymorphism and mutations in p53 were not associated with worse prognosis in this cohort of patients with primary stage T1 urinary bladder carcinoma. However, patients with abnormal p16 expression and a mutated p53 gene had a higher rate of and a shorter time to progression, and p53 gene mutation was associated with an abnormal immunohistochemistry for p53 at a cut-off of 50%.

    Fulltekst (pdf)
    fulltext
  • 19.
    Rosell, Johan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Bengtsson, Nils-Olof
    Umeå University Hospital, Sweden .
    Fornander, Tommy
    Karolinska University Hospital, Sweden .
    Hatschek, Thomas
    Karolinska University Hospital, Sweden .
    Lindman, Henrik
    University of Uppsala Hospital, Sweden .
    Malmstrom, Per-Olof
    Skåne University Hospital, Sweden .
    Wallgren, Arne
    Sahlgrens University Hospital, Sweden .
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Carstensen, John
    Linköpings universitet, Institutionen för medicin och hälsa, Hälsa och samhälle. Linköpings universitet, Hälsouniversitetet.
    Effects of adjuvant tamoxifen therapy on cardiac disease: results from a randomized trial with long-term follow-up2013Inngår i: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 138, nr 2, s. 467-473Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tamoxifen is associated with a reduced risk of coronary heart disease (CHD). However, there are few reports on long-term effects. Using data from a large Swedish randomized trial of 5 and 2 years of adjuvant tamoxifen in women with early breast cancer, we here present results on morbidity and mortality from cardiac diseases during treatment and long-term after treatment. A total of 4,150 patients were breast cancer recurrence-free after 2 years. Data from the Swedish National Hospital Discharge Registry combined with information from the Swedish Cause of Death Registry were used to define events of disease. Hazard ratios were estimated using Cox regression. Patients assigned to 5 years in comparison with 2 years of postoperative tamoxifen experienced a reduced incidence of CHD [hazard ratio (HR), 0.83; 95 % CI 0.70-1.00], especially apparent during the active treatment period (HR 0.65; 95 % CI 0.43-1.00). The mortality from CHD was significantly reduced (HR 0.72; 95 % CI 0.53-0.97). During the active treatment, the morbidity of other heart diseases was also significantly reduced (HR 0.40; 95 % CI 0.25-0.64) but not after treatment stopped (HR 1.06; 95 % CI 0.87-1.30). Similar results were seen for both heart failure and atrial fibrillation/flutter. As compared to 2 years of therapy, 5 years of postoperative tamoxifen therapy prevents CHD as well as other heart diseases. The risk reduction is most apparent during the active treatment period, and later tends to diminish.

  • 20.
    Rosell, Johan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Nordenskjöld, Bo
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Bengtsson, Nils-Olof
    Umeå University Hospital, Sweden .
    Fornander, Tommy
    Karolinska University Hospital, Sweden .
    Hatschek, Thomas
    Karolinska University Hospital, Sweden .
    Lindman, Henrik
    University of Uppsala Hospital, Sweden .
    Malmstrom, Per-Olof
    Skåne University Hospital, Sweden .
    Wallgren, Arne
    Sahlgrens University Hospital, Sweden .
    Stål, Olle
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Carstensen, John
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för hälso- och sjukvårdsanalys. Linköpings universitet, Hälsouniversitetet.
    Effects of adjuvant tamoxifen therapy on the incidence of secondary cancer: results from a randomized trial with long term follow-up2014Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    BACKGROUND

    Tamoxifen is a well-established endocrine treatment for breast cancer. We here present results with respect to second primary cancer from a large randomized trial of 5 and 2 years of adjuvant tamoxifen. Breast cancer distant recurrence and mortality are also reported.

    METHODS

    Our study included 4128 postmenopausal patients with early stage breast cancer who were alive and free of breast cancer recurrence after 2 years of tamoxifen therapy. They were randomized to receive three more years of therapy or stop tamoxifen. In the comparison of 5 years versus 2 years of postoperative tamoxifen treatment hazard ratios were estimated using Cox regression for different follow-up periods defined as: During treatment (2-5 years) and after treatment (5-10 years, 10-15 years, > 5 years, > 10 years and > 15 years).

    RESULTS

    In the five years group the incidence of lung cancer was halved (hazard ratio [HR], 0.45, 95% confidence interval [95% CI], 0.27-0.77 [P = .0038]), and lung cancer mortality was decreased. An increased risk was observed for endometrial cancer (HR, 1.83; 95% CI, 1.19-2.81 [P = .0059]), but this risk appeared to decrease over time. The risk of contralateral breast cancer was decreased (HR, 0.73; 95% CI, 0.56-0.96 [P = .022]), also in the period after treatment stopped. In the five years group, the risk of distant recurrence was decreased, and statistically significant reductions were observed both during treatment and in the five year period after treatment stopped. The breast cancer mortality was reduced, especially during the post-treatment phase.

    CONCLUSIONS

    In this randomized study, tamoxifen substantially reduces the risk of new cancer both in contralateral breast and in lung up to 10 years after treatment stopped.

  • 21.
    Sjödahl, Rune
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Kirurgiska kliniken US.
    Rosell, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Starkhammar, Hans
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Onkologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Onkologiska kliniken US.
    Causes of death after surgery for colon cancer-impact of other diseases, urgent admittance, and gender2013Inngår i: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 48, nr 10, s. 1160-1165Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objective. In patients with colon cancer, high age and comorbidity is common. In this population-based retrospective study we have investigated causes of death and the influence of urgent operation, and gender on survival. Material and methods. Medical records of 413 patients with verified colon cancer were reviewed. The diagnosis was made during 2000-2006 and operation was performed in 385 patients (93%). Results. The overall 5-year survival after surgery was 48.3%. At the end of the follow-up, 128 patients (54.9%) had verified colon cancer when they died but 105 patients (45.1%) had no signs of colon cancer. Their 5-year survival was 5.5% and 41.9%, respectively (p andlt; 0.0001). Median survival time was significantly shorter after urgent compared with elective admittance, 20.7 months versus 77.9 months, and the 5-year survival 32.4% versus 57.9% (p = 0.0001). The tumor stage at operation was more favorable in patients dying with no signs of colon cancer than in those dying with cancer regarding stage I-II (66.7% versus 16.4%), and stage IV (1.0% versus 53.1%), but not regarding stage III (30.5% versus 29.7%). The overall survival in women who were operated was longer than in men (p = 0.045) as well as survival after elective admittance (p = 0.013). Conclusion. After a median follow-up of 56.1 months almost half of the patients who were dead had died from other causes than colon cancer. Ten percent of those patients had an incorrectly reported diagnosis of colon cancer as cause of death. Urgent admittance was associated with reduced survival time. The median survival time was longer in women than in men.

  • 22.
    Sörenson, Sverre
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Lungmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Lungmedicinska kliniken US. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Allergicentrum US.
    Fohlin, Helena
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för hälso- och vårdutveckling, Regionalt cancercentrum.
    Lindgren, Andrea
    Linköpings universitet, Institutionen för medicin och hälsa, Internmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Allergicentrum US.
    Lindskog, Magnus
    Uppsala University, Sweden .
    Bergman, Bengt
    Sahlgrens University Hospital, Sweden .
    Sederholm, Christer
    Linköpings universitet, Institutionen för medicin och hälsa, Lungmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Lungmedicinska kliniken US.
    Ek, Lars
    Skåne University Hospital, Sweden .
    Lamberg, Kristina
    University of Uppsala Hospital, Sweden .
    Clinchy, Birgitta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Predictive role of plasma vascular endothelial growth factor for the effect of celecoxib in advanced non-small cell lung cancer treated with chemotherapy2013Inngår i: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 49, nr 1, s. 115-120Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Aim of the study: The primary purpose of this study is to investigate if pretreatment plasma levels of vascular endothelial growth factor (VEGF) are predictive of the effect of celecoxib on survival in advanced non-small cell lung cancer (NSCLC) treated with palliative chemotherapy. A secondary objective is to describe the course of plasma VEGF levels during and after treatment with cytotoxic chemotherapy combined with celecoxib or placebo. less thanbrgreater than less thanbrgreater thanMethods: In a previously published double-blind multicenter phase III trial, 316 patients with NSCLC stage IIIB or IV and World Health Organisation (WHO) performance status 0-2 were randomised to receive celecoxib 400 mg b.i.d. or placebo in combination with two-drug platinum-based chemotherapy. Chemotherapy cycle length was three weeks and planned duration of chemotherapy was four cycles. Celecoxib was given for a maximum of one year but was stopped earlier in case of disease progression or prohibitive toxicity. In a subset of patients, plasma VEGF levels were examined at onset of treatment and at 6, 12 and 20 weeks. less thanbrgreater than less thanbrgreater thanResults: VEGF levels at start of treatment were obtained in 107 patients at four study sites. The median value was 70 pg/ml. Mean values declined during the first 12 weeks and then increased at 20 weeks. A subpopulation treatment effect pattern plot (STEPP) analysis showed an inverse relationship between initial plasma VEGF and the impact of celecoxib on survival with zero effect at 200 pg/ml. The effect on survival by celecoxib in the whole subset of patients was positive (hazard ratio (HR)=0.64 [confidence interval (CI) 0.43-0.95], p=0.028). less thanbrgreater than less thanbrgreater thanConclusion: Low pretreatment plasma levels of VEGF appear to be predictive of a positive effect of celecoxib on survival.

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