| 1. |
- Fransson, Per, et al.
(författare)
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Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer (HYPO-RT-PC) : patient-reported quality-of-life outcomes of a randomised, controlled, non-inferiority, phase 3 trial
- 2021
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Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 22:2, s. 235-245
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The HYPO-RT-PC trial compared conventionally fractionated radiotherapy with ultra-hypofractionated radiotherapy in patients with localised prostate cancer. Ultra-hypofractionation was non-inferior to conventional fractionation regarding 5-year failure-free survival and toxicity. We aimed to assess whether patient-reported quality of life (QOL) differs between conventional fractionation and ultra-hypofractionation up to 6 years after treatment in the HYPO-RT-PC trial.METHODS: HYPO-RT-PC is a multicentre, open-label, randomised, controlled, non-inferiority, phase 3 trial done in 12 centres (seven university hospitals and five county hospitals) in Sweden and Denmark. Inclusion criteria were histologically verified intermediate-to-high-risk prostate cancer (defined as T1c-T3a with one or two of the following risk factors: stage T3a; Gleason score ≥7; and prostate-specific antigen 10-20 ng/mL with no evidence of lymph node involvement or distant metastases), age up to 75 years, and WHO performance status 0-2. Participants were randomly assigned (1:1) to conventional fractionation (78·0 Gy in 39 fractions, 5 days per week for 8 weeks) or ultra-hypofractionation (42·7 Gy in seven fractions, 3 days per week for 2·5 weeks) via a minimisation algorithm with stratification by trial centre, T-stage, Gleason score, and prostate-specific antigen. QOL was measured using the validated Prostate Cancer Symptom Scale (PCSS) and European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30) at baseline, the end of radiotherapy, months 3, 6, 12, and 24 after radiotherapy, every other year thereafter up to 10 years, and at 15 years. The primary endpoint (failure-free survival) has been reported elsewhere. Here we report QOL, a secondary endpoint analysed in the per-protocol population, up to 6 years after radiotherapy. The HYPO-RT-PC trial is registered with the ISRCTN registry, ISRCTN45905321.FINDINGS: Between July 1, 2005, and Nov 4, 2015, 1200 patients were enrolled and 1180 were randomly assigned (conventional fractionation n=591, ultra-hypofractionation n=589); 1165 patients (conventional fractionation n=582, ultra-hypofractionation n=583) were included in this QOL analysis. 158 (71%) of 223 patients in the conventional fractionation group and 146 (66%) of 220 in the ultra-hypofractionation group completed questionnaires at 6 years. The median follow-up was 48 months (IQR 25-72). In seven of ten bowel symptoms or problems the proportion of patients with clinically relevant deteriorations at the end of radiotherapy was significantly higher in the ultra-hypofractionation group than in the conventional fractionation group (stool frequency [p<0·0001], rush to toilet [p=0·0013], flatulence [p=0·0013], bowel cramp [p<0·0001], mucus [p=0·0014], blood in stool [p<0·0001], and limitation in daily activity [p=0·0014]). There were no statistically significant differences in the proportions of patients with clinically relevant acute urinary symptoms or problems (total 14 items) and sexual functioning between the two treatment groups at end of radiotherapy. Thereafter, there were no clinically relevant differences in urinary, bowel, or sexual functioning between the groups. At the 6-year follow-up there was no difference in the incidence of clinically relevant deterioration between the groups for overall urinary bother (43 [33%] of 132 for conventional fractionation vs 33 [28%] of 120 for ultra-hypofractionation; mean difference 5·1% [95% CI -4·4 to 14·6]; p=0·38), overall bowel bother (43 [33%] of 129 vs 34 [28%] of 123; 5·7% [-3·8 to 15·2]; p=0·33), overall sexual bother (75 [60%] of 126 vs 59 [50%] of 117; 9·1% [-1·4 to 19·6]; p=0·15), or global health/QOL (56 [42%] of 134 vs 46 [37%] of 125; 5·0% [-5·0 to 15·0]; p=0·41).INTERPRETATION: Although acute toxicity was higher for ultra-hypofractionation than conventional fractionation, this long-term patient-reported QOL analysis shows that ultra-hypofractionation was as well tolerated as conventional fractionation up to 6 years after completion of treatment. These findings support the use of ultra-hypofractionation radiotherapy for intermediate-to-high-risk prostate cancer.
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| 2. |
- Widmark, Anders, et al.
(författare)
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Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer : 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial
- 2019
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 394:10196, s. 385-395
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hypofractionated radiotherapy for prostate cancer has gained increased attention due to its proposed high radiation-fraction sensitivity. Recent reports from studies comparing moderately hypofractionated and conventionally fractionated radiotherapy support the clinical use of moderate hypofractionation. To date, there are no published randomised studies on ultra-hypofractionated radiotherapy. Here, we report the outcomes of the Scandinavian HYPO-RTPC phase 3 trial with the aim to show non-inferiority of ultra-hypofractionation compared with conventional fractionation.Methods: In this open-label, randomised, phase 3 non-inferiority trial done in 12 centres in Sweden and Denmark, we recruited men up to 75 years of age with intermediate-to-high-risk prostate cancer and a WHO performance status between 0 and 2. Patients were randomly assigned to ultra-hypofractionation (42.7 Gy in seven fractions, 3 days per week for 2.5 weeks) or conventional fractionated radiotherapy (78.0 Gy in 39 fractions, 5 days per week for 8 weeks). No androgen deprivation therapy was allowed. The primary endpoint was time to biochemical or clinical failure, analysed in the per-protocol population. The prespecified non-inferiority margin was 4% at 5 years, corresponding to a critical hazard ratio (HR) limit of 1.338. Physician-recorded toxicity was measured according to the Radiation Therapy Oncology Group (RTOG) morbidity scale and patient-reported outcome measurements with the Prostate Cancer Symptom Scale (PCSS) questionnaire. This trial is registered with the ISRCTN registry, number ISRCTN45905321.Findings: Between July 1, 2005, and Nov 4, 2015, 1200 patients were randomly assigned to conventional fractionation (n=602) or ultra-hypofractionation (n=598), of whom 1180 (591 conventional fractionation and 589 ultra-hypofractionation) constituted the per-protocol population. 1054 (89%) participants were intermediate risk and 126 (11%) were high risk. Median follow-up time was 5.0 years (IQR 3.1-7.0). The estimated failure-free survival at 5 years was 84% (95% CI 80-87) in both treatment groups, with an adjusted HR of 1.002 (95% CI 0.758-1.325; log-rank p=0.99). There was weak evidence of an increased frequency of acute physician-reported RTOG grade 2 or worse urinary toxicity in the ultra-hypofractionation group at end of radiotherapy (158 [28%] of 569 patients vs 132 [23%] of 578 patients; p=0.057). There were no significant differences in grade 2 or worse urinary or bowel late toxicity between the two treatment groups at any point after radiotherapy, except for an increase in urinary toxicity in the ultra-hypofractionation group compared to the conventional fractionation group at 1-year follow-up (32 [6%] of 528 patients vs 13 [2%] of 529 patients; (p=0.0037). We observed no differences between groups in frequencies at 5 years of RTOG grade 2 or worse urinary toxicity (11 [5%] of 243 patients for the ultra-hypofractionation group vs 12 [5%] of 249 for the conventional fractionation group; p=1.00) and bowel toxicity (three [1%] of 244 patients vs nine [4%] of 249 patients; p=0.14). Patient-reported outcomes revealed significantly higher levels of acute urinary and bowel symptoms in the ultra-hypofractionation group compared with the conventional fractionation group but no significant increases in late symptoms were found, except for increased urinary symptoms at 1-year follow-up, consistent with the physician-evaluated toxicity.Interpretation: Ultra-hypofractionated radiotherapy is non-inferior to conventionally fractionated radiotherapy for intermediate-to-high risk prostate cancer regarding failure-free survival. Early side-effects are more pronounced with ultra-hypofractionation compared with conventional fractionation whereas late toxicity is similar in both treatment groups. The results support the use of ultra-hypofractionation for radiotherapy of prostate cancer. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
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| 3. |
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| 4. |
- Andersson, Anne, 1966-, et al.
(författare)
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Family history of cancer as a risk factor for second malignancies after Hodgkin's lymphoma
- 2008
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 98:5, s. 1001-1005
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Tidskriftsartikel (refereegranskat)abstract
- This study estimated the risk of second primary malignancies after Hodgkin's lymphoma (HL) in relation to family history of cancer, age at diagnosis and latency, among 6946 patients treated for HL in Sweden in 1965–1995 identified through the Swedish Cancer Register (SCR). First-degree relatives (FDRs) to the HL patients and their malignancies were then ascertained together with their malignancies through the Multi-Generation Registry and SCR. The HL patient cohort was stratified on the number of FDRs with cancer, and standardised incidence ratios (SIRs) of developing SM were analysed. In the HL cohort, 781 SM were observed 1 year or longer after HL diagnosis. The risk for developing SM increased with the number of FDRs with cancer, SIRs being 2.26, 3.01, and 3.45 with 0, 1, or ≥2 FDRs with cancer, respectively. Hodgkin's lymphoma long-term survivors treated at a young age with a family history of cancer carry an increased risk for developing SM and may represent a subgroup where standardised screening for the most common cancer sites could be offered in a stringent surveillance programme.
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| 5. |
- Andersson, Anne, 1966-, et al.
(författare)
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High risk of cardiovascular side effects after treatment of Hodgkin's lymphoma : is there a need for intervention in long-term survivors?
- 2021
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Ingår i: Upsala Journal of Medical Sciences. - : Upsala Medical Society. - 0300-9734 .- 2000-1967. ; 126
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hodgkin lymphoma (HL) patients have a good prognosis after adequate treatment. Previous treatment with mantle field irradiation has been accompanied by an increased long-term risk of cardiovascular disease (CVD). This study identified co-morbidity factors for the development of cardiovascular side effects and initiated an intervention study aimed to decrease morbidity and mortality of CVD in HL survivors.Design: Hodgkin lymphoma patients aged ≤45 years diagnosed between 1965 and 1995 were invited to participate. In total, 453 patients completed a questionnaire that addressed co-morbidity factors and clinical symptoms. Of these, 319 accepted to participate in a structured clinical visit. The statistical analyses compared individuals with CVD with those with no CVD.Results: Cardiovascular disease was reported by 27.9%. Radiotherapy (odds ratio [OR]: 3.27), hypertension and hypercholesterolemia were shown to be independent risk factors for the development of CVD. The OR for CVD and valve disease in patients who received radiotherapy towards mediastinum was 4.48 and 6.07, respectively. At clinical visits, 42% of the patients were referred for further investigation and 24% of these had a cardiac ultrasound performed due to previously unknown heart murmurs.Conclusion: Radiotherapy towards mediastinum was an independent risk factor for CVD as well as hypercholesterolemia and hypertension. A reasonable approach as intervention for this cohort of patients is regular monitoring of hypertension and hypercholesterolemia and referral to adequate investigation when cardiac symptoms appear. Broad knowledge about the side effects from radiotherapy in the medical community and well-structured information regarding late side effects to the patients are all reasonable approaches as late effects can occur even 40 years after cancer treatment.
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| 6. |
- Andersson, Anne, 1966-, et al.
(författare)
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Long-term risk of cardiovascular disease in Hodgkin lymphoma survivors : retrospective cohort analyses and a concept for prospective intervention
- 2009
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 124:8, s. 1914-1917
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have shown increased cardiovascular mortality as late side effects in Hodgkin lymphoma (HL) patients. This study identifies stratifying risk factors for surveillance and defines concepts for a clinical feasible and noninvasive prospective protocol for intervention of cardiovascular side effects. HL patients diagnosed between 1965 and 1995 (n = 6.946) and their first-degree relatives (FDR) were identified through the Swedish Cancer Registry and the Swedish Multigeneration Registry. For the HL and FDR cohort, in-patient care for cardiovascular disease (CVD) was registered through the Hospital Discharge Registry, Sweden. Standard incidence ratios of developing CVD for the HL cohort were calculated. A markedly increased risk for in-patient care of CVD was observed in HL patients with HL diagnosed at age 40 years or younger and with more than 10 years follow-up. In the HL survivors, a family history of congestive heart failure (CHF) and coronary artery disease (CAD) increased the risk for these diseases. The Swedish Hodgkin Intervention and Prevention study started in 2007. In the pilot feasibility study for prospective intervention (47 patients), about 25% of the cases had side effects and laboratory abnormalities. These patients were referred to a cardiologist or general practitioner. In the prospective cohort, a positive family history for CHF or CAD could be a stratifying risk factor when setting up a surveillance model. The prospective on-going study presents an intervention model that screens and treats for comorbidity factors. This article also presents an overview of the study concept.
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| 7. |
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| 8. |
- Davis, Faith, et al.
(författare)
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Second primary tumors following a diagnosis of meningioma in Sweden, 1958-1997.
- 2007
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Ingår i: Neuroepidemiology. - : S. Karger AG. - 1423-0208 .- 0251-5350. ; 29:1-2, s. 101-106
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Tidskriftsartikel (refereegranskat)abstract
- This study quantifies the risk of second primary tumors following a diagnosis of meningioma. 12,012 meningiomas and 926 second primary cancers were identified (ICD7, path code 461) between1958 and 1997 using Swedish Cancer Registry data. Standardized incidence ratios (SIRs) and exact 95% confidence intervals (CIs) were calculated. An elevated risk of any second primary cancer diagnosis (SIR = 1.2, 95% CI = 1.1–1.3) was observed. Elevated and statistically significant SIRs were observed for renal cancer (SIR = 1.6), melanoma (SIR = 1.7), thyroid cancer (SIR = 2.6) and brain tumors (SIR = 2.6). A consistent pattern of risk over time supports the evaluation of common risk factor profiles for renal, melanoma and thyroid cancers. Radiation exposures increase the risk of these rare tumors, so quantifying the cumulative and shared effects of environmental and treatment exposures is of further interest.
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| 9. |
- Egberg Thyme, Karin, 1943-, et al.
(författare)
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Art therapy and self-image : A 5-year follow-up art therapy RCT study of women diagnosed with breast cancer
- 2022
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Ingår i: Palliative & Supportive Care. - : Cambridges Institutes Press. - 1478-9515 .- 1478-9523. ; 20:4, s. 482-490
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Tidskriftsartikel (refereegranskat)abstract
- Mål: Denna uppföljningsstudie om upplevd självbild och psykofysisk nöd/psykiska symptom baserades på en ranomiserad kontrollerad studie av konstterapi på kvinnor med bröstcancer.Metod: Syftet var att undersöka de långsiktiga effekterna av tidsbegränsad konstterapi med hjälp av instrumenten Strukturanalys av socialt beteende (SASB) och Symptom Check List-90 (SCL-90).Resultat: Tre anslutningskluster i SASB visade signifikanta förändringar efter terapin: Autonomt jag (kluster 1), Accepterande själv (kluster 2) och Älskande själv (kluster 3). Klusterna 2 och 3 fortsatte att förändras till förmån för interventionsgruppen vid den 5-åriga uppföljningen. Det fanns inga signifikanta skillnader i SCL-90-resultaten mellan interventionsgruppen och kontrollgruppen i uppföljningsstudien.Betydelse av resultat: Konstterapiinterventionen var både terapeutisk och psyko-pedagogisk. Slutsatsen av denna studie är att närmar sig känslor genom tidsbegränsad konstterapi verkar ha en långvarig effekt på det vidhäftande beteende som visas i SASB-modellen efter intervention, och denna effekt förblev 5 år senare.
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| 10. |
- Elmstedt, Sixten, et al.
(författare)
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Cancer patients hospitalised in the last week of life risk insufficient care quality : a population-based study from the Swedish Register of Palliative Care
- 2019
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Ingår i: Acta Oncologica. - : Taylor & Francis Group. - 0284-186X .- 1651-226X. ; 58:4, s. 432-438
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Tidskriftsartikel (refereegranskat)abstract
- Background: One-quarter of all cancer deaths in Sweden occur in hospitals. If the place of death affects the quality of end-of-life (EOL) is largely unknown.Methods: This population-based, retrospective study included all adults cancer deaths reported to the Swedish Register of Palliative Care in 2011-2013 (N = 41,729). Hospital deaths were compared to deaths occurring in general or specialised palliative care, or in nursing homes with respect to care quality indicators in the last week of life. Odds ratios (OR) with 95% confidence intervals (CI) were calculated with specialised palliative home care as reference.Results: Preferred place of death was unknown for 63% of hospitalised patients and consistent with the actual place of death in 25% compared to 97% in palliative home care. Hospitalised patients were less likely to be informed when death was imminent (OR: 0.3; CI: 0.28-0.33) as were their families (OR: 0.51; CI: 0.46-0.57). Validated screening tools were less often used in hospitals for assessment of pain (OR: 0.32; CI: 0.30-0.34) or other symptoms (OR: 0.31; CI: 0.28-0.34) despite similar levels of EOL symptoms. Prescriptions of as needed drugs against anxiety (OR: 0.27; CI: 0.24-0.30), nausea (OR: 0.19; CI: 0.17-0.21), or pulmonary secretions (OR: 0.29; CI: 0.26-0.32) were less prevalent in hospitals. Bereavement support was offered after 57% of hospital deaths compared to 87-97% in palliative care units and 72% in nursing homes.Conclusions: Dying in hospital was associated with inferior end-of-life care quality among cancer patients in Sweden.
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| 11. |
- Emilsson, Sofia, et al.
(författare)
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Support group participation during the post-operative radiotherapy period increases levels of coping resources among women with breast cancer.
- 2012
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Ingår i: European Journal of Cancer Care. - : Hindawi Limited. - 0961-5423 .- 1365-2354. ; 21:5, s. 591-598
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Tidskriftsartikel (refereegranskat)abstract
- Support group participation during the post-operative radiotherapy period increases levels of coping resources among women with breast cancer Being diagnosed with breast cancer is a traumatic experience that can elevate levels of distress and cause depletion of coping resources in many of the disease's victims. This non-randomised case-control study among breast cancer patients undergoing radiotherapy indicates that participation in a support group that focuses on communication and mutual sharing between its member's has positive effects and increases levels of coping resources assessed with the Coping Resources Inventory (CRI). Results of the CRI showed a significant difference between the study group and control group in the social domain at the second occasion of measurement (P= 0.007) and in the emotional domain at the third occasion (P= 0.028). Within the study group, over time, increased levels of coping resources reached significant levels concerning the emotional domain at the second occasion (P= 0.025). Conversely, coping resources were decreased in the same domain within the control group over time, at the third occasion (P= 0.053). Additionally, anxiety and depression were assessed using the Hospital Anxiety and Depression Scale, showing no difference between the groups. This study shows that participation in a support group during post-operative radiotherapy can be socially and emotionally strengthening because of the opportunity for the patients to mutually share experiences.
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| 12. |
- Faraz, Mahmood, et al.
(författare)
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LRIG1 gene copy number analysis by ddPCR and correlations to clinical factors in breast cancer
- 2020
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Ingår i: BMC Cancer. - : BioMed Central. - 1471-2407. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) copy number alterations and unbalanced gene recombination events have been reported to occur in breast cancer. Importantly, LRIG1 loss was recently shown to predict early and late relapse in stage I-II breast cancer.Methods: We developed droplet digital PCR (ddPCR) assays for the determination of relative LRIG1 copy numbers and used these assays to analyze LRIG1 in twelve healthy individuals, 34 breast tumor samples previously analyzed by fluorescence in situ hybridization (FISH), and 423 breast tumor cytosols.Results: Four of the LRIG1/reference gene assays were found to be precise and robust, showing copy number ratios close to 1 (mean, 0.984; standard deviation, +/-0.031) among the healthy control population. The correlation between the ddPCR assays and previous FISH results was low, possibly because of the different normalization strategies used. One in 34 breast tumors (2.9%) showed an unbalanced LRIG1 recombination event. LRIG1 copy number ratios were associated with the breast cancer subtype, steroid receptor status, ERBB2 status, tumor grade, and nodal status. Both LRIG1 loss and gain were associated with unfavorable metastasis-free survival; however, they did not remain significant prognostic factors after adjustment for common risk factors in the Cox regression analysis. Furthermore, LRIG1 loss was not significantly associated with survival in stage I and II cases.Conclusions: Although LRIG1 gene aberrations may be important determinants of breast cancer biology, and prognostic markers, the results of this study do not verify an important role for LRIG1 copy number analyses in predicting the risk of relapse in early-stage breast cancer.
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| 13. |
- Fransson, Per, et al.
(författare)
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Reliability and responsiveness of a prostate cancer questionnaire for radiotherapy-induced side effects
- 2001
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Ingår i: Supportive Care in Cancer. - : Springer. - 0941-4355 .- 1433-7339. ; 9:3, s. 187-198
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Tidskriftsartikel (refereegranskat)abstract
- Few self-assessment cancer-specific questionnaires / modules have yet been developed for radiotherapy-induced side effects. The aim of the present study was to test the reliability and responsiveness of a prostate cancer (PC)specific questionnaire. Thirty-one patients with PC graded their urinary and intestinal symptoms and their sexual function on the questionnaire. A doctor and a nurse performed a structured interview and graded the patient's symptoms with the same questions. The procedure was performed at both the start and the end of the treatment. A high concordance regarding symptom detection was seen between the patient, nurse and the doctor. The inter-rater test shows intraclass correlation coefficient (ICC) values above 0.60 in all scales. The internal reliability exceeded the lower limit (Cronbach alpha > 0.70) for all scales. The test-retest gave acceptable reliability for all scales (ICC greater than or equal to 0.60). All scales indicated increased problems during radiotherapy. The questionnaire was proven to be valid for the evaluations of urinary and intestinal problems and for sexual function in PC patients.
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| 14. |
- Fritzson, Anna, et al.
(författare)
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Association between parenteral fluids and symptoms in hospital end-of-life care : an observational study of 280 patients
- 2015
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Ingår i: BMJ Supportive & Palliative Care. - : BMJ. - 2045-435X .- 2045-4368. ; 5:2, s. 160-168
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate whether dying patients receiving parenteral fluids (PF) suffer from more or less symptoms than patients who do not receive PF. Today's evidence on how PF affects palliative patients' symptoms is very scarce. Nevertheless, 40% of the patients who die expectedly in Swedish hospitals receive PF during their last 24 h of life.METHODS: A historical cohort study of medical records was performed. Of the 530 patients who were reported to have died expectedly at hospital in Västerbotten county (Sweden) between 1 January 2011 and 30 June 2012, 140 cases who had received PF and 140 controls who had not received PF were identified by stratified randomisation and matched by age, sex and main disease. The groups were compared regarding documented presence of dyspnoea, respiratory secretions, anxiety, nausea and confusion during the last 24 h and the last week of life.RESULTS: The prevalence of documented dyspnoea in the PF groups was higher than in the non-PF groups (51% vs 22% last 24 h, p<0.0001; 70% vs 45% last 7 days, p<0.001). The proportions of patients suffering from dyspnoea increased with larger administered volume. Although our main hypothesis--that the prevalence of respiratory secretions would be higher in the PF group--was not confirmed, we found a tendency in that direction (63% vs 50% last week, p=0.072). No clinically significant differences in anxiety, nausea or confusion were found.CONCLUSIONS: There is an association between PF administration and increased frequency of documented dyspnoea for terminally ill patients in their last week of life.
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| 15. |
- Försti, A, et al.
(författare)
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Polymorphisms in the genes of the urokinase plasminogen activation system in relation to colorectal cancer
- 2007
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Ingår i: Annals of Oncology. - : Oxford University Press. - 0923-7534 .- 1569-8041. ; 18:12, s. 1990-1994
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Tidskriftsartikel (refereegranskat)abstract
- Background: Extracellular matrix degradation, mediated by the urokinase plasminogen activation (uPA) system, is a critical step in tumor invasion and metastasis. High tumor levels of uPA and its inhibitor PAI-1 have been correlated with poor cancer prognosis. We examined four single nucleotide polymorphisms (SNPs) with a potential effect on expression of genes in the uPA system for their role in colorectal cancer susceptibility and prognosis.Patients and methods: We genotyped the SNPs in 308 Swedish incident colorectal cancer patients with up to 16 years of follow-up and in 585 age- and sex-matched controls. We evaluated the associations between genotypes and colorectal cancer and Dukes' stage. Survival probabilities were compared between different subgroups.Results: Patients with PAI-1 –675 5G/5G genotype had better survival than patients with 4G/4G or 4G/5G genotypes when they had Dukes' stage A or B tumors (P = 0.023 and P = 0.015, respectively). No statistically significant association was observed between the SNPs and the risk of colorectal cancer or Dukes' stage.Conclusions: Our results suggest a role for the PAI-1 genotype in colorectal cancer prognosis, but further studies are needed to evaluate the impact of our finding in the clinic.
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| 16. |
- Försti, Asta, et al.
(författare)
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Polymorphisms in the transforming growth factor beta 1 pathway in relation to colorectal cancer progression
- 2010
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Ingår i: Genes, Chromosomes and Cancer. - New York : Liss. - 1045-2257 .- 1098-2264. ; 49:3, s. 270-281
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Tidskriftsartikel (refereegranskat)abstract
- Transforming growth factor beta1 (TGFB1) acts as a growth inhibitor of normal colonic epithelial cells, however, as a tumor promoter of colorectal cancer (CRC) cells. To explore the association between genetic polymorphisms in the TGFB1 pathway and CRC susceptibility and clinical outcome, we carried out a case-control study on a Swedish population of 308 CRC cases and 585 age- and gender-matched controls. The cases were sampled prospectively and had up to 16 years follow-up, making the study material particularly suitable for survival analysis. On the basis of their reported or predicted functional effect, nine single-nucleotide polymorphisms (TGFB1: Leu10Pro; TGFBR1: 9A/6A and IVS7G+24A; FURIN: C-229T; THBS1: T+42C; LTBP1L: C-256G; LTBP4: T-893G and Thr750Ala; BAMBI: T-779A) were selected for genotyping. We evaluated the associations between genotypes and CRC and Dukes' stage. Survival probabilities were compared between different subgroups. The observed statistically significant associations included a decreased CRC risk for TGFBR1 IVS7G+24A minor allele carriers (odds ratio (OR): 0.72, 95% confidence interval (CI): 0.53-0.97), less aggressive tumors with Dukes' stage A+B for carriers of LTBP4 Thr750Ala and BAMBI T-779A minor alleles (OR: 0.58, 95%CI: 0.36-0.93 and OR: 0.51, 95%CI: 0.29-0.89, respectively) and worse survival for FURIN C-229T heterozygotes (hazard ratio: 1.63, 95%CI: 1.08-2.46). As this is the first study about the influence of the polymorphisms in the TGFB1 pathway on CRC progression, further studies in large independent cohorts are warranted.
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| 17. |
- Gkekas, Ioannis, 1981-, et al.
(författare)
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Sporadic deficient mismatch repair in colorectal cancer increases the risk for non-colorectal malignancy : a European multicenter cohort study
- 2024
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Ingår i: Journal of Surgical Oncology. - : John Wiley & Sons. - 0022-4790 .- 1096-9098. ; 129:7, s. 1295-1304
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: Disparities between tumors arising via different sporadic carcinogenetic pathways have not been studied systematically. This retrospective multicenter cohort study evaluated the differences in the risk for non-colorectal malignancy between sporadic colorectal cancer (CRC) patients from different DNA mismatch repair status.Methods: A retrospective European multicenter cohort study including in total of 1706 CRC patients treated between 1996 and 2019 in three different countries. The proficiency (pMMR) or deficiency (dMMR) of mismatch repair was determined by immunohistochemistry. Cases were analyzed for tumor BRAFV600E mutation, and BRAF mutated tumors were further analyzed for hypermethylation status in the promoter region of MLH1 to distinguish between sporadic and hereditary cases. Swedish and Finish patients were matched with their respective National Cancer Registries. For the Czech cohort, thorough scrutiny of medical files was performed to identify any non-colorectal malignancy within 20 years before or after the diagnosis of CRC. Poisson regression analysis was performed to identify the incidence rates of non-colorectal malignancies. For validation purposes, standardized incidence ratios were calculated for the Swedish cases adjusted for age, year, and sex.Results: Of the 1706 CRC patients included in the analysis, 819 were female [48%], median age at surgery was 67 years [interquartile range: 60–75], and sporadic dMMR was found in 188 patients (11%). Patients with sporadic dMMR CRC had a higher incidence rate ratio (IRR) for non-colorectal malignancy before and after diagnosis compared to patients with a pMMR tumor, in both uni- (IRR = 2.49, 95% confidence interval [CI] = 1.89–3.31, p = 0.003) and multivariable analysis (IRR = 2.24, 95% CI = 1.67–3.01, p = 0.004). This association applied whether or not the non-colorectal tumor developed before or after the diagnosis of CRC in both uni- (IRR = 1.91, 95% CI = 1.28–2.98, p = 0.004), (IRR = 2.45, 95% CI = 1.72–3.49, p = 0.004) and multivariable analysis (IRR = 1.67,95% CI = 1.05–2.65, p = 0.029), (IRR = 2.35, 95% CI = 1.63–3.42, p = 0.005), respectively.Conclusion: In this retrospective European multicenter cohort study, patients with sporadic dMMR CRC had a higher risk for non-colorectal malignancy than those with pMMR CRC. These findings indicate the need for further studies to establish the need for and design of surveillance strategies for patients with dMMR CRC.
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| 18. |
- Kinhult, Sara, et al.
(författare)
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Regional variation i användningen av TTF vid glioblastombehandling : [Regional variation in usage of TTF (Optune)]
- 2023
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Ingår i: Läkartidningen. - : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 120:120
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Tidskriftsartikel (refereegranskat)abstract
- The standard treatment of glioblastoma, an aggressive brain tumour, includes radiotherapy combined with temozolomide. Based on a randomised trial, showing five months increased survival, TTF has been introduced in the management of patients with good performance status. Data from the Swedish national quality registry for CNS tumours have been analysed for TTF usage. The results demonstrate that 65 percent of the patients accepted treatment with TTF. More than half of the treated patients interrupted treatment due to low compliance or their own wish. Median treatment time was 164 days, with a range from 0 to 774 days. There was a large variation between different regions in how many patients were offered TTF treatment. A non-significant trend to better survival was seen for the group of TTF-treated patients compared to individually matched controls. In summary, TTF is a new treatment for glioblastoma, with potential to prolong survival also in real world patients. Today, the treatment is not offered equally to all patients, despite national guidelines.
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| 19. |
- Kinhult, Sara, et al.
(författare)
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Regional variation i användningen av TTF vid glioblastombehandling
- 2023
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Ingår i: Lakartidningen. - 0023-7205. ; 120
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Tidskriftsartikel (refereegranskat)abstract
- The standard treatment of glioblastoma, an aggressive brain tumour, includes radiotherapy combined with temozolomide. Based on a randomised trial, showing five months increased survival, TTF has been introduced in the management of patients with good performance status. Data from the Swedish national quality registry for CNS tumours have been analysed for TTF usage. The results demonstrate that 65 percent of the patients accepted treatment with TTF. More than half of the treated patients interrupted treatment due to low compliance or their own wish. Median treatment time was 164 days, with a range from 0 to 774 days. There was a large variation between different regions in how many patients were offered TTF treatment. A non-significant trend to better survival was seen for the group of TTF-treated patients compared to individually matched controls. In summary, TTF is a new treatment for glioblastoma, with potential to prolong survival also in real world patients. Today, the treatment is not offered equally to all patients, despite national guidelines.
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| 20. |
- Kinhult, Sara, et al.
(författare)
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Regional variation in usage of TTF (Optune) Regional variation i användningen av TTF vid glioblastombehandling : [Regional variation in usage of TTF (Optune)]
- 2023
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Ingår i: Läkartidningen. - : Sveriges läkarförbund. - 0023-7205 .- 1652-7518. ; 120
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Tidskriftsartikel (refereegranskat)abstract
- The standard treatment of glioblastoma, an aggressive brain tumour, includes radiotherapy combined with temozolomide. Based on a randomised trial, showing five months increased survival, TTF has been introduced in the management of patients with good performance status. Data from the Swedish national quality registry for CNS tumours have been analysed for TTF usage. The results demonstrate that 65 percent of the patients accepted treatment with TTF. More than half of the treated patients interrupted treatment due to low compliance or their own wish. Median treatment time was 164 days, with a range from 0 to 774 days. There was a large variation between different regions in how many patients were offered TTF treatment. A non-significant trend to better survival was seen for the group of TTF-treated patients compared to individually matched controls. In summary, TTF is a new treatment for glioblastoma, with potential to prolong survival also in real world patients. Today, the treatment is not offered equally to all patients, despite national guidelines.
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| 21. |
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| 22. |
- Kohler, Corina, et al.
(författare)
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Assessing the value of CAN-gene mutations using MALDI-TOF MS
- 2011
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Ingår i: Journal of Cancer Research and Clinical Oncology. - : Springer Science and Business Media LLC. - 0171-5216 .- 1432-1335. ; 137:8, s. 1239-1244
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Tidskriftsartikel (refereegranskat)abstract
- Sjöblom et al./Wood et al. already showed that the vast majority of CAN-genes are mutated at very low frequency. Due to the fact that we only found one mutation in our cohort, we therefore assume that at the selected loci, mutations might be low-frequency events and therefore, more rarely detectable. However, further evaluation of the CAN-gene mutations in larger cohorts should be the aim of further studies.
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| 23. |
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| 24. |
- Lindgren, Moa, et al.
(författare)
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Type IV collagen as a potential biomarker of metastatic breast cancer
- 2021
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Ingår i: Clinical and Experimental Metastasis. - : Springer. - 0262-0898 .- 1573-7276. ; 38:2, s. 175-185
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Tidskriftsartikel (refereegranskat)abstract
- No reliable, non-invasive biomarker of metastatic breast cancer (mBC) exists: circulating CA15-3 (cCA15-3) is the marker mostly used to monitor mBC. Circulating collagen IV (cCOLIV) has been evaluated in other metastatic cancers and has been found to be a promising biomarker. The overarching aim of this study was to evaluate cCOLIV as a potential biomarker in patients with mBC. The first aim was to determine the levels of cCOL IV and cCA15-3 in patients with healthy controls, primary breast cancer (pBC) and mBC. The second aim was to compare levels of cCOLIV and cCA15-3 in patients with different metastatic sites of BC. The third aim was to investigate the prognostic value of cCOLIV and cCA15-3 for mBC patients. The fourth aim was to analyse whether a combination of the two biomarkers was more accurate in detecting mBC than a single marker. Lastly, we investigated the tissue expression levels of COLIV in BC bone metastases (BM) and liver metastases (LM). Plasma levels of cCOLIV and cCA15-3 from healthy controls and patients with pBC and mBC were measured. COLIV expression in tissue from patients with LM and BM was analysed using immunohistochemistry. Clinical and survival data were collected from medical charts. The levels of cCOLIV and cCA15-3 were significantly elevated in mBC patients compared with healthy controls and pBC patients. No differences in cCOLIV and cCA15-3 levels were found based on the metastatic site. High levels of cCOLIV, but not cCA15-3, correlated with poorer survival. cCOLIV alone and the combination of cCA15-3 and cCOLIV were superior to cCA15-3 at detecting mBC. COL IV was highly expressed in the tissue of LM and BM. Our study suggests that cCOLIV is a potential marker to monitor patients with BC.
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| 25. |
- Lindskog, Magnus, et al.
(författare)
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Old age as risk indicator for poor end-of-life care quality : a population-based study of cancer deaths from the Swedish Register of Palliative Care
- 2015
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 51:10, s. 1331-1339
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Tidskriftsartikel (refereegranskat)abstract
- Background: If patient age affects the quality of end-of-life care in cancer is unknown. Using data from a population-based register of palliative care in Sweden, we addressed this question. Methods: This nation-wide study focused on the last week of life of adults dying from cancer in 2011-2012, based on data reported to a national quality register for end-of-life care (N = 26,976). We specifically investigated if age-dependent differences were present with respect to thirteen indicators of palliative care quality. Patients were categorised in one out of five pre-defined age groups. Odds ratios (OR) with 95% confidence intervals (CIs), adjusted for type of end-of-life care unit, were calculated using logistic regression, with the oldest group as reference. Findings: Age-dependent differences in implementation rate were detected for ten out of thirteen end-of-life care quality indicators, most of which were progressively less well met with each increment in age group. Compared to elderly cancer patients, young patients were more often informed about imminent death, (OR, 3.9; 95% CI 2.5-5.9, p < 0.001), were more often systematically assessed for the presence and severity of pain (OR, 1.6; 95% CI 1.2-2.1, p < 0.001) or other symptoms (OR, 1.4; 95% CI 1.0-1.9, p = 0.044), were more likely to be assessed by palliative care consultation services (OR, 4.3; 95% CI 3.3-5.7, p < 0.001) and to have injections prescribed as needed against pain (OR, 3.4; 95% CI 1.3-9.4, p = 0.016), anxiety (OR, 3.8; 95% CI 2.0-7.1, p < 0.001) or nausea (OR, 3.6; 95% CI 2.3-5.7, p < 0.001). The families of young patients were more likely to be informed about imminent death ( OR, 2.6; 95% CI 1.5-4.3, p = 0.001) and to be offered bereavement support ( OR, 4.6; 95% CI 2.7-7.8, p < 0.001). Interpretation: Old age is a risk indicator for poor end-of-life care quality among cancer patients in Sweden. Funding: The executive committee of the National Quality Registries in Sweden.
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