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2. |
- Aamand Grabau, Dorthe, et al.
(author)
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The prevalence of immunohistochemically determined oestrogen receptor positivity in primary breast cancer is dependent on the choice of antibody and method of heat-induced epitope retrieval - prognostic implications?
- 2013
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In: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 52:8, s. 1657-1666
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Journal article (peer-reviewed)abstract
- Background. Oestrogen receptor (ER) status is important for the choice of systemic treatment of breast cancer patients. However, most data from randomised trials on the effect of adjuvant endocrine therapy according to ER status are based on the cytosol methods. Comparisons with immunohistochemical methods have given similar results. The aim of the present study was to examine whether different ER antibodies and heat-induced epitope retrieval (HIER) methods influence the prevalence of ER-positivity in primary breast cancer. Material and methods. This study is based on patients included in a clinical trial designed to compare the effect of two years of adjuvant tamoxifen versus no adjuvant systemic treatment in premenopausal women. From 1986 to 1991, 564 patients from two study centres in Sweden were enrolled and randomised. Patients were randomised independently of ER status. In the present study, ER status was assessed on tissue microarrays with the three different ER antibody/HIER combinations: 1D5 in citrate pH 6 (n = 390), SP1 in Tris pH 9 (n = 390) and PharmDx in citrate pH 6 (n = 361). Results. At cut-offs of 1% and 10%, respectively, the prevalence of ER-positivity was higher with SP1 (75% and 72%) compared with 1D5 (68% and 66%) and PharmDx (66% and 62%). At these cut-offs, patients in the discordant groups (SP1-positive and 1D5-negative) seem to have a prognosis intermediate between those of the double-positive and double-negative groups. Comparison with the ER status determined by the cytosol-based methods in the discordant group also showed an intermediate pattern. The repeatability was good for all antibodies and cut-offs, with overall agreement andgt;= 93%. Conclusion. The present study shows that the choice of antibody and HIER method influences the prevalence of ER-positivity. We suggest that this be taken into consideration when choosing a cut-off for clinical decision making.
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3. |
- Abdulla, Maysaa, et al.
(author)
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A population-based study of cellular markers in R-CHOP treated diffuse large B-cell lymphoma patients
- 2016
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In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 55:9-10, s. 1126-1131
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Journal article (peer-reviewed)abstract
- Aim: To determine the prognostic significance of co-expression of MYC, BCL-2 and BCL-6 proteins in combination with other biomarkers and clinical characteristics within a population-based cohort of diffuse large B-cell lymphoma (DLBCL) patients uniformly treated with R-CHOP.Patients and methods: The immunohistochemical (IHC) expression of CD10, BCL-2, BCL-6, MUM1, MYC, CD5, CD30, Ki-67 and p53 was evaluated in a retrospective, population-based study comprising 188 DLBCL patients treated with R-CHOP and diagnosed in Sweden between 2002 and 2012.Results: Patients had a median age at diagnosis of 64 years (26-85 years) with a male:female ratio of 1.4:1. Approximately half (52%) of the patients presented with an International Prognostic Index (IPI) age adjusted (IPIaa)2. Median follow-up time was 51 months (range 0.4-158) and the five-year lymphoma-specific survival (LSS) was 76%, five-year overall survival (OS) was 65% and five-year progression-free survival (PFS) was 61%. A high Ki-67 value was found in 59% of patients, while p53 overexpression was detected in 12% of patients and MYC, BCL-2 and BCL-6 expression were detected in 42%, 55% and 74% of patients, respectively. IPIaa2 (p=0.002), Ki-6770% (p=0.04) and p53 overexpression50% (p=0.02) were associated with inferior LSS and OS. Co-expression of both MYC (>40%) and BCL-2 (>70%) proteins was detected in 27% of patients and correlated with a significantly inferior LSS (p=0.0002), OS (p=0.009) and PFS (p=0.03). In addition, triple expression of MYC, BCL-2 and BCL-6, also correlated with a significantly inferior LSS (p=0.02).Conclusion: Concurrent expression of MYC and BCL-2 proteins, as detected by IHC, was strongly associated with an inferior survival in DLBCL patients treated with R-CHOP. Other markers affecting survival were triple expression of MYC, BCL-2 and BCL-6, IPIaa, high Ki-67 and p53 overexpression.
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- Abdulla, Maysaa, et al.
(author)
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PD-L1 and IDO1 are potential targets for treatment in patients with primary diffuse large B-cell lymphoma of the CNS
- 2021
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In: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 60:4, s. 531-538
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Journal article (peer-reviewed)abstract
- BackgroundProgrammed cell death 1 (PD-1) and its ligands PD-L1 and PD-L2, as well as Indoleamine 2,3-deoxygenase (IDO1) can be expressed both by tumor and microenvironmental cells and are crucial for tumor immune escape. We aimed to evaluate the role of PD-1, its ligands and IDO1 in a cohort of patients with primary diffuse large B-cell lymphoma of the CNS (PCNSL).Material and methodsTissue microarrays (TMAs) were constructed in 45 PCNSL cases. RNA extraction from whole tissue sections and RNA sequencing were successfully performed in 33 cases. Immunohistochemical stainings for PD-1, PD-L1/paired box protein 5 (PAX-5), PD-L2/PAX-5 and IDO1, and Epstein-Barr virus encoding RNA (EBER) in situ hybridization were analyzed.ResultsHigh proportions of PD-L1 and PD-L2 positive tumor cells were observed in 11% and 9% of cases, respectively. High proportions of PD-L1 and PD-L2 positive leukocytes were observed in 55% and 51% of cases, respectively. RNA sequencing revealed that gene expression of IDO1 was high in patients with high proportion of PD-L1 positive leukocytes (p = .01). Protein expression of IDO1 in leukocytes was detected in 14/45 cases, in 79% of these cases a high proportion of PD-L1 positive leukocytes was observed. Gene expression of IDO1 was high in EBER-positive cases (p = .0009) and protein expression of IDO1 was detected in five of six EBER-positive cases.ConclusionOur study shows a significant association between gene and protein expression of IDO1 and protein expression of PD-L1 in the tumor microenvironment of PCNSL, possibly of importance for prediction of response to immunotherapies.
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7. |
- Adami, HO
(author)
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The prostate cancer pseudo-epidemic
- 2010
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In: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 49:3, s. 298-304
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Journal article (other academic/artistic)
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10. |
- Ahlin, Cecilia, et al.
(author)
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Aberrant expression of cyclin E in low-risk node negative breast cancer
- 2008
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In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 47:8, s. 1539-1545
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Journal article (peer-reviewed)abstract
- Background. Cyclin E is a cell cycle regulatory protein which occurs in G1, peaks in late G1 and is degraded in early S-phase. Cyclin E overexpression appears to be an independent prognostic factor for overall survival in breast cancer. Material and Methods. Nuclear cyclin A is a reliable marker for S-and G2-phases. Consequently, aberrant expression of cyclin E can be detected by simultaneous immunostainings for cyclin A and cyclin E. Studies have shown that aberrant cyclin E might provide additional prognostic information compared to that of cyclin E alone. This study aimed to investigate cyclin E and aberrant cyclin E expression in low-risk node negative breast cancer. We compared women that died from their breast cancer (n=17) with women free from relapse>8 years after initial diagnosis (n=24). All women had stage I, low risk breast cancer. The groups were matched regarding tumour size, receptor status, adjuvant chemotherapy and tumour differentiation. Tumour samples were analysed regarding expression of cyclin A, cyclin E and double-stained tumour cells using immunoflourescence staining and digital microscopy. Results. No differences were seen regarding expression of cyclin E or aberrant cyclin E in cases compared to controls. Discussion. We conclude that neither cyclin E nor aberrant cyclin E is a prognostic factor in low-risk node negative breast cancer patients.
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11. |
- Ahlström, Håkan, et al.
(author)
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An experimental model for pharmacokinetic studies of monoclonal antibodies in human colonic cancer
- 1987
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In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 26:6, s. 447-451
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Journal article (peer-reviewed)abstract
- An experimental model consisting of athymic rats carrying human colonic tumours from cell line LS 174T in both hind legs was used. 125I-labelled anti-carcinoembryonic antigen (anti-CEA) monoclonal antibodies were injected intra-arterially (i.a.), either alone (21 rats) or together with degradable starch microspheres (6 rats). As a control, an irrelevant antibody was injected i.a., alone (6 rats) or together with microspheres (3 rats). An intra-arterial injection was given on the side bearing one tumour in each rat, while the contralateral tumour served as an 'intravenous' control. The rats were submitted to external gamma measurements daily for four days. On the fourth day they were killed and pieces from the tumours and from various organs were examined by in vitro measurements. The results indicate strong expression of CEA in LS 174T cells grafted to athymic rats. No lasting enhancement of the tumour uptake was achieved by intra-arterial injection of antibodies as compared with the control tumours.
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12. |
- Ahlström, Håkan, et al.
(author)
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Enhanced uptake of intra-arterially injected anti-CEA monoclonal antibodies in human colonic cancer after mannitol infusion in an experimental model
- 1987
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In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 26:6, s. 453-458
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Journal article (peer-reviewed)abstract
- In a previous report athymic rats carrying transplanted human colonic tumours from cell line LS 174T in both hind legs were injected intra-arterially (i.a.) with 125I-labelled anti-carcinoembryonic (anti-CEA) monoclonal antibodies. The i.a. injection was given on one side bearing a tumour in each rat, while the contralateral tumour served as an 'intravenous' control. In the same experimental model and treated in the same way, 10 rats were injected i.a. with anti-CEA monoclonal antibodies after an i.a. mannitol infusion. In both groups of rats external gamma measurements were performed daily for four days. On the fourth day the rats were killed and pieces of the tumours and of various organs were weighed and the activity was determined with a gamma-counter. The tumour uptake of antibodies was significantly enhanced after mannitol infusion.
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13. |
- Ahlström, Håkan, et al.
(author)
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The spatial distribution of parenterally administered monoclonal antibodies against CEA in a human colorectal tumour xenograft
- 1989
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In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 28:1, s. 81-86
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Journal article (peer-reviewed)abstract
- A recently developed experimental model consisting of athymic rats carrying human colonic tumours from the cell line LS 174 T in both hind legs was used. 125I-labelled anti-carcinoembryonic (anti-CEA) monoclonal antibodies were injected either intra-arterially after a bolus injection of mannitol, or intra-peritoneally with or without mannitol. On the fourth day the rats were killed and pieces from the tumours and various organs were measured in a well scintillation counter. Tumour pieces were then submitted to autoradiography and immunohistochemistry for examination of the antibody distribution at the cellular level. In all examined tumours injected with anti-CEA antibodies, most of the antibodies were located in the periphery close to fibrovascular septa. It appears, in addition to the specificity of the antibody for the CEA, that the tumour vascular permeability and anatomy are of utmost importance for tumour targeting in this experimental model with the particular antibody used.
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18. |
- Albertsson, Per, 1964, et al.
(author)
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Dose effects of continuous vinblastine chemotherapy on mammalian angiogenesis mediated by VEGF-A.
- 2008
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In: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 47:2, s. 293-300
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Journal article (peer-reviewed)abstract
- Low-dose continuous or metronomic chemotherapy with several agents can exert significant antiangiogenic effects, as shown in preclinical studies. Therapy of this kind is generally well tolerated compared with conventional chemotherapy with high, temporally spaced out bolus doses. A critical point emerges when the effects on angiogenesis of low-toxic metronomic doses of chemotherapeutics in preclinical studies are to be transferred to clinical protocols, as there is a risk that a virtually non-toxic dose might also be ineffective; clearly, dose-effect data are important. We therefore sought to investigate whether a dose-dependent response exists in metronomic vinblastine chemotherapy. The surrogate tumor-free rat mesentery model, allowing the study of antiangiogenic effects per se, was used. Following systemically administered metronomic chemotherapy, it closely reflects the indirectly assessed antiangiogenic and growth-retarding effects in a syngenic cancer model. VEGF-A, which is a central proangiogenic factor in most tumors, was administered i.p. to induce angiogenesis in the mesenteric test tissue and, using morphometry, the angiogenesis-modulating effects of vinblastine were assessed in terms of objective quantitative variables. We report that continuous vinblastine treatment with an apparently non-toxic dose (1.0 mg/kg/week or 0.143 mg/kg/day) for 10 days, and a dose that substantially inhibited the physiologic body-weight gain (2.0 mg/kg/week or 0.286 mg/kg/day) for 6 days, demonstrates a dose-response relationship; the high dose significantly suppresses angiogenesis. To our knowledge, no previous study has reported on a dose-dependent antiangiogenic effect by continuous or metronomic vinblastine treatment in a mammalian in vivo model.
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19. |
- Albertsson, Per, 1964, et al.
(author)
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Low-dose continuous 5-fluorouracil infusion stimulates VEGF-A-mediated angiogenesis.
- 2009
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In: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 48:3, s. 418-25
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Journal article (peer-reviewed)abstract
- BACKGROUND: Tumor growth is angiogenesis-dependent. Animal studies have demonstrated that frequent administration of chemotherapeutics may have marked antiangiogenic effects and improved antitumor effects, with less severe toxic side-effects than intermittent maximum tolerated dose chemotherapy. Currently, research focused on low-dose antiangiogenic chemotherapy is increasing. We have recently reported that certain chemotherapeutics, including 5-fluorouracil (5-FU), may in fact stimulate angiogenesis in the tumor-free rat mesenteric window assay. The aim of the present study was to extend the investigation of the angiogenesis-modulating effects of 5-FU by prolonging the continuous infusion treatment time. METHOD: Angiogenesis was induced in the mesenteric test tissue in adult male Sprague-Dawley rats by i.p. injection of VEGF-A, which is a key angiogenic factor in most tumors. During the subsequent angiogenesis, 5-FU was delivered continuously for 14 days by an osmotic pump implanted subcutaneously. The angiogenic response was analyzed by morphometry in the mesenteric windows. RESULTS: The 14-days continuous infusion of 5-FU significantly stimulated angiogenesis. Thus the possibility that the previously reported surprising proangiogenic effect of 5-FU reflected an insufficiently long treatment period can be ruled out. CONCLUSION: The finding that continuously infused 5-FU is able to stimulate angiogenesis in the present rat model of angiogenesis warrants investigation of the mechanisms behind this unexpected finding. It may further have implications for the choice of antiangiogenic chemotherapeutic schedule used for cancer patients.
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20. |
- Albertsson, Per, 1964, et al.
(author)
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On metronomic chemotherapy: modulation of angiogenesis mediated by VEGE-A
- 2006
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In: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 45:2, s. 144-55
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Journal article (peer-reviewed)abstract
- Tumors are angiogenesis dependent. Preclinical studies have shown that well-tolerated continuous low dose, i.e. metronomic, chemotherapy can exert significant antiangiogenic effects per se and thereby a greater antitumor influence than conventional chemotherapy with high, spaced-out bolus doses. There are however, no means of quantitatively assessing the antiangiogenic effect of chemotherapy in tumors. We therefore used a surrogate tumor-free, non-surgical rat mesentery model and quantitatively studied the dose effect of metronomic treatment with cisplatin, cyclophosphamide, doxorubicin, fluorouracil and paclitaxel on VEGF-A-mediated angiogenesis, a characteristic of tumors. Cyclophosphamide and paclitaxel treatment exerted significant dose-dependent antiangiogenic effects, whereas doxorubicin treatment produced insignificant effects. By contrast, metronomic cisplatin and fluorouracil treatment occasionally significantly stimulated angiogenesis in a dose-dependent, non-linear manner. To our knowledge, this is the first report of metronomic chemotherapy stimulating angiogenesis in vivo. The data suggest that the angiogenic response to cisplatin, cyclophosphamide, fluorouracil and paclitaxel was significantly influenced by the presence of antioxidants in the vehicles or when co-treated with N-acetylcystein, a widely used free-radical scavenger. The data relating to the metronomic scheduling were compared with bolus treatment data for the identical agent formulations in the same experimental model. Cisplatin, cyclophosphamide and paclitaxel caused approximately the same overall, agent-specific angiogenesis-modulating effects following metronomic and bolus treatments. Moreover, apparently secondary delayed effects of chemotherapy affected capillary sprouting.
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21. |
- Albrow, Rebecca, et al.
(author)
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Interventions to improve cervical cancer screening uptake amongst young women : A systematic review
- 2014
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In: Acta Oncologica. - London : Informa Healthcare. - 0284-186X .- 1651-226X. ; 53:4, s. 445-451
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Research review (peer-reviewed)abstract
- Objectives. In view of declining screening uptake in young women, this review aims to summarise the available evidence relating to interventions designed to increase cervical screening uptake amongst women aged <= 35 years.Methods. Electronic databases were searched and further articles located by manual searches. Study designs employing a valid comparison group and including women aged <= 35 years published through 2012 were considered. Data was extracted on the uptake from either screening programme statistics or as reported by the study subjects. A narrative synthesis was undertaken for each category of interventions identified.Results. Ninety-two records were screened with 36 articles retrieved for further assessment. Four studies met the inclusion criteria, two of which evaluated more than one intervention. One of the studies evaluated the use of a modified invitation letter and reported no significant increase in uptake compared to a standard invitation. Three studies investigated the use of a reminder letter, with two reporting a positive effect on screening uptake in women aged 24-34. Three studies were included which supported the use of physician and telephone reminders. One study on HPV self-sampling reported a positive effect when compared with a reminder letter.Conclusions. There is a lack of randomised controlled trials designed to specifically address falling cervical screening uptake in amongst young women. Cervical screening programmes need to look beyond the use of invitation/reminders letters in this group of women to develop interventions which attempt to overcome as many barriers to uptake as possible.
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22. |
- Alevronta, Eleftheria, et al.
(author)
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Dose-response relationships for an atomized symptom of fecal incontinence after gynecological radiotherapy.
- 2013
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In: Acta oncologica (Stockholm, Sweden). - : Taylor & Francis. - 1651-226X .- 0284-186X. ; 52:4, s. 719-26
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Journal article (peer-reviewed)abstract
- Purpose. The aim of this study was to investigate what bowel organ and delivered dose levels are most relevant for the development of 'emptying of all stools into clothing without forewarning' so that the related dose-responses could be derived as an aid in avoiding this distressing symptom in the future. Material and methods. Of the 77 gynecological cancer survivors treated with radiotherapy (RT) for gynecological cancer, 13 developed the symptom. The survivors were treated between 1991 and 2003. The anal-sphincter region, the rectum, the sigmoid and the small intestines were all delineated and the dose-volume histograms were exported for each patient. The dose-volume parameters were estimated fitting the data to the Relative Seriality (RS), the Lyman and the generalized Equivalent Uniform Dose (gEUD) model. Results. The dose-response parameters for all three models and four organs at risk (OARs) were estimated. The data from the sigmoid fits the studied models best: D50 was 58.8 and 59.5 Gy (RS, Lyman), γ50 was 1.60 and 1.57 (RS, Lyman), s was 0.32, n was 0.13 and a was 7.7 (RS, Lyman, gEUD). The estimated volume parameters indicate that the investigated OARs behave serially for this endpoint. Our results for the three models studied indicate that they have the same predictive power (similar LL values) for the symptom as a function of the dose for all investigated OARs. Conclusions. In our study, the anal-sphincter region and sigmoid fit our data best, but all OARs were found to have steep dose-responses for 'emptying of all stools into clothing without forewarning' and thus, the outcome can be predicted with an NTCP model. In addition, the dose to the four studied OARs may be considered when minimizing the risk of the symptom.
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23. |
- Alevronta, Eleftheria, et al.
(author)
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Dose-response relationships of the sigmoid for urgency syndrome after gynecological radiotherapy.
- 2018
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In: Acta oncologica (Stockholm, Sweden). - 1651-226X .- 0284-186X. ; 57:10, s. 1352-1358
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Journal article (peer-reviewed)abstract
- To find out what organs and doses are most relevant for 'radiation-induced urgency syndrome' in order to derive the corresponding dose-response relationships as an aid for avoiding the syndrome in the future.From a larger group of gynecological cancer survivors followed-up 2-14years, we identified 98 whom had undergone external beam radiation therapy but not brachytherapy and not having a stoma. Of those survivors, 24 developed urgency syndrome. Based on the loading factor from a factor analysis, and symptom frequency, 15 symptoms were weighted together to a score interpreted as the intensity of radiation-induced urgency symptom. On reactivated dose plans, we contoured the small intestine, sigmoid colon and the rectum (separate from the anal-sphincter region) and we exported the dose-volume histograms for each survivor. Dose-response relationships from respective risk organ and urgency syndrome were estimated by fitting the data to the Probit, RS, LKB and gEUD models.The rectum and sigmoid colon have steep dose-response relationships for urgency syndrome for Probit, RS and LKB. The dose-response parameters for the rectum were D50: 51.3, 51.4, and 51.3Gy, γ50=1.19 for all models, s was 7.0e-09 for RS and n was 9.9×107 for LKB. For Sigmoid colon, D50 were 51.6, 51.6, and 51.5Gy, γ50 were 1.20, 1.25, and 1.27, s was 2.8 for RS and n was 0.079 for LKB.Primarily the dose to sigmoid colon as well as the rectum is related to urgency syndrome among gynecological cancer survivors. Separate delineation of the rectum and sigmoid colon in order to incorporate the dose-response results may aid in reduction of the incidence of the urgency syndrome.
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24. |
- Alexandersson, Nathalie, et al.
(author)
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Determinants of variable resource use for multidisciplinary team meetings in cancer care
- 2018
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In: Acta Oncologica. - 0284-186X. ; 57:5, s. 675-680
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Journal article (peer-reviewed)abstract
- Background: Multidisciplinary team meetings (MDTMs) have developed into standard of care to provide expert opinion and to grant evidence-based recommendations on diagnostics and treatment of cancer. Though MDTMs are associated with a range of benefits, a growing number of cases, complex case discussion and an increasing number of participants raise questions on cost versus benefit. We aimed to determine cost of MDTMs and to define determinants hereof based on observations in Swedish cancer care. Methods: Data were collected through observations of 50 MDTMs and from questionnaire data from 206 health professionals that participated in these meetings. Results: The MDTMs lasted mean 0.88 h and managed mean 12.6 cases with mean 4.2 min per case. Participants were mean 8.2 physicians and 2.9 nurses/other health professionals. Besides the number of cases discussed, meeting duration was also influenced by cancer diagnosis, hospital type and use of video facilities. When preparatory work, participation and post-MDTM work were considered, physicians spent mean 4.1 h per meeting. The cost per case discussion was mean 212 (range 91–595) EUR and the cost per MDTM was mean 2675 (range 1439–4070) EUR. Conclusions: We identify considerable variability in resource use for MDTMs in cancer care and demonstrate that 84% of the total cost is derived from physician time. The variability demonstrated underscores the need for regular and structured evaluations to ensure cost effective MDTM services.
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25. |
- Alexandra, Wide, et al.
(author)
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Fertility-related information received by young women and men with cancer : a population-based survey
- 2021
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In: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 60:8, s. 976-983
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Journal article (peer-reviewed)abstract
- Background: Infertility is a well-known sequela of cancer treatment. Despite guidelines recommending early discussions about risk of fertility impairment and fertility preservation options, not all patients of reproductive age receive such information.Aims: This study aimed to investigate young adult cancer patients' receipt of fertility-related information and use of fertility preservation, and to identify sociodemographic and clinical factors associated with receipt of information.Materials and methods: A population-based cross-sectional survey study was conducted with 1010 young adults with cancer in Sweden (response rate 67%). The inclusion criteria were: a previous diagnosis of breast cancer, cervical cancer, ovarian cancer, brain tumor, lymphoma or testicular cancer between 2016 and 2017, at an age between 18 and 39 years. Data were analyzed using logistic regression models.Results: A majority of men (81%) and women (78%) reported having received information about the potential impact of cancer/treatment on their fertility. A higher percentage of men than women reported being informed about fertility preservation (84% men vs. 40% women, p < .001) and using gamete or gonadal cryopreservation (71% men vs. 15% women, p < .001). Patients with brain tumors and patients without a pretreatment desire for children were less likely to report being informed about potential impact on their fertility and about fertility preservation. In addition, being born outside Sweden was negatively associated with reported receipt of information about impact of cancer treatment on fertility. Among women, older age (>35 years), non-heterosexuality and being a parent were additional factors negatively associated with reported receipt of information about fertility preservation.Conclusion: There is room for improvement in the equal provision of information about fertility issues to young adult cancer patients.
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26. |
- Anderlind, Eva, et al.
(author)
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Will haptic feedback speed up medical imaging? An application to radiation treatment planning
- 2008
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In: Acta Oncologica. - OSLO, Norge : Taylor & Francis. - 0284-186X .- 1651-226X. ; 47:1, s. 32-37
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Journal article (peer-reviewed)abstract
- Haptic technology enables us to incorporate the sense of touch into computer applications, providing an additional input/output channel. The purpose of this study was to examine if haptic feedback can help physicians and other practitioners to interact with medical imaging and treatment planning systems. A haptic application for outlining target areas (a key task in radiation therapy treatment planning) was implemented and then evaluated via a controlled experiment with ten subjects. Even though the sample size was small, and the application only a prototype, results showed that haptic feedback can significantly increase (p0.05) the speed of outlining target volumes and organs at risk. No significant differences were found regarding precision or perceived usability. This promising result warrants further development of a full haptic application for this task. Improvements to the usability of the application as well as to the forces generated have been implemented and an experiment with more subjects is planned.
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29. |
- Andersson, Inger, 1964, et al.
(author)
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Health related quality of life in stem cell transplantation: clinical and psychometric validation of the questionnaire module, High Dose Chemotherapy (HDC-19).
- 2008
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In: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 47:2, s. 275-85
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Journal article (peer-reviewed)abstract
- The objective of this study was to assess the psychometric properties of the HDC-19, a module questionnaire for assessing symptoms and problems of patients undergoing stem cell transplantation (SCT) following high-dose chemotherapy (HDC). It consists of 19 questions and was developed for use in conjunction with EORTC QLQ-C30. Psychometric evaluations were performed according to guidelines recommended by the EORTC. The principal component analyses suggested that nine of the HDC-19 items could be reduced to four components (sexual functioning, future health perspectives, skin irritations and joint/muscle pain). Multitrait scaling analysis showed that most item-scale correlation coefficients met the standards of convergent (>0.40) and discriminant validity. Test-retest reliability coefficients between assessments at inclusion and admission were high, indicating that perceived health status remained virtually unchanged during this period. As expected, correlations between admission and one month after transplantation were considerably lower. The internal consistency of the multi-item scales was also satisfactory, (Cronbach's alpha 0.59-0.87). Overall, the known-groups comparisons showed smaller differences between designated groups than expected. As expected, changes in the HDC-19 mirrored changes in QLQ-C30 'global quality of life'. These results lend support to the validity of the HDC-19 as a supplementary questionnaire for assessing specific health-related quality of life (HRQOL) issues relevant for SCT patients.
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30. |
- Andersson, J, et al.
(author)
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A population-based study on the first forty-eight breast cancer patients receiving trastuzumab (Herceptin (R)) on a named patient basis in Sweden
- 2002
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In: Acta Oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 41:3, s. 276-281
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Journal article (peer-reviewed)abstract
- Several studies have presented data on the efficacy and tolerability of trastuzumab within clinical trials. As a minority of patients is included in these trials, we undertook this retrospective study to describe trastuzumab therapy in clinical routine and its tolerability. We reviewed the medical records of the first 48 patients in Sweden who received treatment with trastuzumab on a named patient basis with (n = 29) and without (n = 19) chemotherapy. Forty-six patients had metastatic disease and had failed to respond to several prior regimens before starting antibody treatment. Two patients had locally advanced breast cancer failing on given neoadjuvant therapy. Patients with breast cancers with strong (3+) c-erbB-2 overexpression tended to have an improved survival from start of trastuzumab treatment versus those with a moderate (2+) overexpression (p=0.09). Adverse events were registered in 22 patients (46%). The most common and acute side effects were fever and chills (7 patients, 15%). The toxicity seemed reasonable but two patients (4%) suffered serious cardiac events, both of them having received previous treatment with antracyclines.
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31. |
- Andersson, Kristin, et al.
(author)
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The interface of population-based cancer registries and biobanks in etiological and clinical research : current and future perspectives
- 2010
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In: Acta Oncologica. - 0284-186X .- 1651-226X. ; 49:8, s. 1227-1234
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Journal article (peer-reviewed)abstract
- BACKGROUND: The availability of quality assured, population-based cancer registries and biobanks with high quality samples makes it possible to conduct research on large samples sets with long follow-up within a reasonable time frame. Defined quality for both cancer registries and biobanks is essential for enabling high quality biobank-based research. Recent networking projects have brought these infrastructures together to promote the combined use of cancer registries and biobanks in cancer research.MATERIALS AND METHODS: In this report we review the current status and future perspectives of cancer registries and biobanks and how the interface between them should be developed to optimally further cancer research.RESULTS AND DISCUSSION: Major conclusions for future improvements are that the research exploiting cancer registries and biobanks, and the research that is building and optimising the infrastructure, should evolve together for maximally relevant progress. Population-based and sustainable biobanks that continuously and consecutively store all samples ("Biological registries") under strict quality control are needed. There is also a need for increased education, information and visibility of the interdisciplinary sciences required for optimal exploitation of these resources.
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32. |
- Andersson, Ulrika, et al.
(author)
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A comprehensive study of the association between the EGFR and ERBB2 genes and glioma risk
- 2010
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In: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 12, s. 17-17
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Journal article (peer-reviewed)abstract
- Glioma is the most common type of adult brain tumor and glioblastoma, its most aggressive form, has a dismal prognosis. Receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR, ERBB2, ERBB3, ERBB4) family, and the vascular endothelial growth factor receptor (VEGFR), play a central role in tumor progression. We investigated the genetic variants of EGFR, ERBB2, VEGFR and their ligands, EGF and VEGF on glioma and glioblastoma risk. In addition, we evaluated the association of genetic variants of a newly discovered family of genes known to interact with EGFR: LRIG2 and LRIG3 with glioma and glioblastoma risk. Methods. We analyzed 191 tag single nucleotide polymorphisms (SNPs) capturing all common genetic variation of EGF, EGFR, ERBB2, LRIG2, LRIG3, VEGF and VEGFR2 genes. Material from four case-control studies with 725 glioma patients (329 of who were glioblastoma patients) and their 1 610 controls was used. Haplotype analyses were conducted using SAS/Genetics software. Results. Fourteen of the SNPs were significantly associated with glioma risk at p< 0.05, and 17 of the SNPs were significantly associated with glioblastoma risk at p< 0.05. In addition, we found that one EGFR haplotype was related to increased glioblastoma risk at p=0.009, Odds Ratio [OR] = 1.67 (95% confidence interval (CI): 1.14, 2.45). The Bonferroni correction made all p-values non-significant. One SNP, rs4947986 next to the intron/exon boundary of exon 7 in EGFR, was validated in an independent data set of 713 glioblastoma and 2 236 controls, [OR] = 1.42 (95% CI: 1.06,1.91). Discussion. Previous studies show that regulation of the EGFR pathway plays a role in glioma progression but the present study is the first to find that certain genotypes of the EGFR gene may be related to glioblastoma risk. Further studies are required to reinvestigate these findings and evaluate the functional significance.
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33. |
- Andersson, Ulrika, et al.
(author)
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Genetic variants in association studies : review of strengths and weaknesses in study design and current knowledge of impact on cancer risk
- 2009
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In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 48:7, s. 948-954
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Journal article (peer-reviewed)abstract
- Sequencing of the human genome has recently been completed and mapping of the complete genomic variation is ongoing. During the last decade there has been a huge expansion of studies of genetic variants, both with respect to association studies of disease risk and for studies of genetic factors of prognosis and treatments response, i.e., pharmacogenomics. The use of genetics to predict a patient's risk of disease or treatment response is one step toward an improved personalised prevention and screening modality for the prevention of cancer and treatment selection. The technology and statistical methods for completing whole genome tagging of variants and genome wide association studies has developed rapidly over the last decade. After identifying the genetic loci with the strongest, statistical associations with disease risk, future studies will need to further characterise the genotype-phenotype relationship to provide a biological basis for prevention and treatment decisions according to genetic profile. This review discusses some of the general issues and problems of study design; we also discuss challenges in conducting valid association studies in rare cancers such as paediatric brain tumours, where there is support for genetic susceptibility but difficulties in assembling large sample sizes. The clinical interpretation and implementation of genetic association studies with respect to disease risk and treatment is not yet well defined and remains an important area of future research.
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34. |
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35. |
- Angenete, Eva, 1972, et al.
(author)
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Preoperative radiotherapy and extracellular matrix remodeling in rectal mucosa and tumour matrix metalloproteinases and plasminogen components.
- 2009
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In: Acta oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 48:8, s. 1144-1151
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Journal article (peer-reviewed)abstract
- Background. Preoperative radiotherapy reduces recurrence but increases postoperative morbidity. The aim of this study was to explore the effect of radiotherapy in rectal mucosa and rectal tumour extracellular matrix (ECM) by studying enzymes and growth factors involved in ECM remodeling. Materials and methods. Twenty patients with short-term preoperative radiotherapy and 12 control patients without radiotherapy were studied. Biopsies from rectal mucosa and tumour were collected prior to radiotherapy and at surgery. Tissue MMP-1, -2, -9, TIMP-1, uPA, PAI-1, TGF-beta1 and calprotectin were determined by ELISA. Biopsies from irradiated and non-irradiated peritoneal areas were also analysed. Results. Radiotherapy increased the tissue levels of MMP-2 and PAI-1 in both the rectal mucosa and tumours while calprotectin and uPA showed an increase only in the mucosa after irradiation. The increase of calprotectin was due to an influx of inflammatory cells as revealed by immunohistochemistry. Prior to irradiation, the tumour tissues had increased levels of MMP-1, -2, -9, total TGF-beta1, uPA, PAI-1 and calprotectin compared to mucosa, while TIMP-1 and the active TGF-beta1 fraction showed no statistical difference. Conclusions. This study indicates a radiation-induced effect on selected ECM remodeling proteases. This reaction may be responsible for early and late morbidity. Interference of this response might reduce these consequences.
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36. |
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37. |
- Ardenfors, Oscar, et al.
(author)
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Are IMRT treatments in the head and neck region increasing the risk of secondary cancers?
- 2014
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In: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 53:8, s. 1041-1047
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Journal article (peer-reviewed)abstract
- Background. Intensity-modulated radiation therapy (IMRT) has been increasingly employed for treating head and neck (H&N) tumours due to its ability to produce isodoses suitable for the complex anatomy of the region. The aim of this study was to assess possible differences between IMRT and conformal radiation therapy (CRT) with regard to risk of radiation-induced secondary malignancies for H&N tumours. Material and methods. IMRT and CRT plans were made for 10 H&N adult patients and the resulting treatment planning data were used to calculate the risk of radiation-induced malignancies in four different tissues. Three risk models with biologically relevant parameters were used for calculations. The influence of scatter radiation and repeated imaging sessions has also been investigated. Results. The results showed that the total lifetime risks of developing radiation-induced secondary malignancies from the two treatment techniques, CRT and IMRT, were comparable and in the interval 0.9-2.5%. The risk contributions from the primary beam and scatter radiation were comparable, whereas the contribution from repeated diagnostic imaging was considerably smaller. Conclusion. The results indicated that the redistribution of the dose characteristic to IMRT leads to a redistribution of the risks in individual tissues. However, the total levels of risk were similar between the two irradiation techniques considered.
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39. |
- Arheden, A., et al.
(author)
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Real-world data on PD-1 inhibitor therapy in metastatic melanoma
- 2019
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In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 58:7, s. 962-966
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Journal article (peer-reviewed)abstract
- Introduction: Phase III studies of PD-1 inhibitors have demonstrated remarkable improvements in the survival of patients with metastatic melanoma (MM). If these results are generalizable to an unselected patient population treated in clinical routine is unknown. This study aimed to investigate and describe clinical efficacy and safety of PD-1 inhibitors in patients with MM treated in routine clinical practice. Material and methods: A retrospective descriptive study of patients with metastatic or inoperable cutaneous melanoma treated with PD-1 inhibitors at a single institution (Department of Oncology, Sahlgrenska University Hospital) from 1 September 2015 to 31 August 2017. Data were obtained from medical records. Results: A total of 116 patients were included in the analyses. The overall survival (OS) at 12-month follow-up was 70.2% and the median OS was 27.9 months. Patients with BRAF mutated tumors had increased OS, whereas ECOG PS >= 2, LDH > ULN and presence or history of brain metastases (stage M1d) were associated with impaired survival. Immune-related AEs of any grade occurred in 64 (55.2%) patients and 15 (12.9%) patients experienced immune-related AEs of grades 3 and 4. Notably, rheumatic adverse events occurred at a higher rate (15.5%) than previously reported. The occurrence of immune-related AEs was associated with a benefit in OS, while the severity of immune-related AEs did not affect survival, nor did the use of systemic corticosteroids. Conclusions: The efficacy and safety of PD1 inhibitors in routine clinical practice appear comparable to that described in clinical trials.
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40. |
- Armuand, Gabriela M., et al.
(author)
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Women more vulnerable than men when facing risk for treatment-induced infertility : a qualitative study of young adults newly diagnosed with cancer
- 2015
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In: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 54:2, s. 243-252
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Journal article (peer-reviewed)abstract
- BACKGROUND: Being diagnosed with cancer constitutes not only an immediate threat to health, but cancer treatments may also have a negative impact on fertility. Retrospective studies show that many survivors regret not having received fertility-related information and being offered fertility preservation at time of diagnosis. This qualitative study investigates newly diagnosed cancer patients' experiences of fertility-related communication and how they reason about the risk of future infertility.MATERIAL AND METHODS: Informants were recruited at three cancer wards at a university hospital. Eleven women and 10 men newly diagnosed with cancer participated in individual semi-structured interviews focusing on three domains: experiences of fertility-related communication, decision-making concerning fertility preservation, and thoughts and feelings about the risk of possible infertility. Data was analyzed through qualitative content analysis.RESULTS: The analysis resulted in three sub-themes, 'Getting to know', 'Reacting to the risk' and 'Handling uncertainty', and one main theme 'Women more vulnerable when facing risk for infertility', indicating that women reported more negative experiences related to patient-provider communication regarding fertility-related aspects of cancer treatment, as well as negative emotional reactions to the risk of infertility and challenges related to handling uncertainty regarding future fertility. The informants described distress when receiving treatment with possible impact on fertility and used different strategies to handle the risk for infertility, such as relying on fertility preservation or thinking of alternative ways to achieve parenthood. The negative experiences reported by the female informants may be related to the fact that none of the women, but almost all men, had received information about and used fertility preservation.CONCLUSIONS: Women newly diagnosed with cancer seem to be especially vulnerable when facing risk for treatment-induced infertility. Lack of shared decision-making concerning future fertility may cause distress and it is therefore necessary to improve the fertility-related communication targeted to female cancer patients.
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41. |
- Arne, Gabriella, et al.
(author)
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Gastrointestinal stromal tumors (GISTs) express somatostatin receptors and bind radiolabeled somatostatin analogs.
- 2013
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In: Acta oncologica (Stockholm, Sweden). - 1651-226X .- 0284-186X. ; 52:4, s. 783-792
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Journal article (peer-reviewed)abstract
- Background. Gastrointestinal stromal tumors (GISTs) can be effectively treated with tyrosine kinase inhibitors (TKIs). However, some patients with GIST develop drug resistance, and alternative treatment strategies are therefore needed. The aim of this study was to analyze the expression of somatostatin receptors (SSTR) in GIST as a target for peptide receptor-mediated radiotherapy (PRRT). Material and methods. Expression profiling of SSTR1-5 was performed on biopsies from 34 GISTs (16 gastric tumors, 15 small intestinal tumors, and three rectal tumors). SSTR scintigraphy ((111)In-octreotide) and measurement of (111)In activity in tumor specimens was performed in seven patients. Uptake and internalization of (177)Lu- octreotate was studied in primary cell cultures from two patients. Results. Quantitative PCR analysis showed expression of SSTR1 and SSTR2 in the majority of tumors, while SSTR3-5 were expressed at low levels. Immunohistochemical analysis confirmed the presence of SSTR1 and SSTR2 proteins in all GISTs, and SSTR3-5 in a subset of tumors. Diagnostic imaging by SSTR scintigraphy, using (111)In-octreotide, demonstrated tumor uptake of (111)In in three of six GIST patients. Measurement of (111)In activity in excised tumor specimens from five patients gave tumor-to-blood (T/B) activity ratios of between eight and 96. Tumor cells in primary culture (gastric and small intestinal GIST) specifically bound and internalized (177)Lu when incubated with the therapeutic compound (177)Lu-octreotate for 4-48 hours (p < 0.05). Conclusion. Peptide receptor-mediated radiotherapy via SSTR may provide a novel treatment strategy in carefully selected GIST patients with TKI-resistant tumors.
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42. |
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47. |
- Ask, Anders, et al.
(author)
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The potential of proton beam radiation therapy in gastrointestinal cancer
- 2005
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In: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:8, s. 896-903
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Journal article (peer-reviewed)abstract
- A group of Swedish oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours and normal tissues. In gastrointestinal cancers, it is assessed that at least 345 patients, mainly non-resectable rectal cancers, oesophageal and liver cancers, are eligible. Great uncertainties do however exist both in the number of patients with gastrointestinal cancers suitable for radiation therapy, and in the proportion of those where proton beams may give sufficiently better results.
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48. |
- Ask, Anders, et al.
(author)
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The potential of proton beam radiation therapy in head and neck cancer.
- 2005
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In: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 44:8, s. 876-80
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Journal article (peer-reviewed)abstract
- A group of Swedish oncologists and hospital physicists have estimated the number of patients in Sweden suitable for proton beam therapy. The estimations have been based on current statistics of tumour incidence, number of patients potentially eligible for radiation treatment, scientific support from clinical trials and model dose planning studies and knowledge of the dose-response relations of different tumours and normal tissues. In head and neck cancer, including thyroid cancer, it is assessed that at least 300 patients annually will gain sufficiently from proton beam therapy, both to improve tumour control and to decrease toxicity to compensate for the increased treatment costs using protons.
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49. |
- Ask, Samuel, et al.
(author)
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The effect of psychosocial interventions for sexual health in patients with pelvic cancer : a systematic review and meta-analysis
- 2024
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In: Acta Oncologica. - : Medical Journals Sweden AB. - 0284-186X .- 1651-226X. ; 63:1, s. 230-239
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Research review (peer-reviewed)abstract
- Aim: The aim of this systematic review and meta-analysis was to explore and evaluate the effect of psychosocial interventions in improving sexual health outcomes among post-treatment patients with pelvic cancer.Methods: Inclusion and exclusion criteria were pelvic cancer survivors; psychosocial interventions; studies with a control group and measures of sexual health. Five databases were searched for literature along with an inspection of the included studies' reference lists to extend the search. Risk of bias was assessed with the RoB2 tool. Standardised mean difference (SMD) with a random effects model was used to determine the effect size of psychosocial interventions for sexual health in patients with pelvic cancers.Results: Thirteen studies were included, with a total number of 1,541 participants. There was a large heterogeneity regarding the type of psychosocial intervention used with the source found in a leave one out analysis. Six studies showed statistically significant improvements in sexual health, while three showed positive but non-significant effects. The summary effect size estimate was small SMD = 0.24 (95% confidence interval [CI]: 0.05 to 0.42, p = 0.01).Discussion: There is limited research on psychosocial interventions for sexual health in pelvic cancer patients. There are also limitations in the different pelvic cancer diagnoses examined. Commonly, the included articles examined physical function rather than the whole sexual health spectrum. The small effect sizes may in part be due to evaluation of psychosocial interventions by measuring physical dysfunction. Future research should broaden sexual health assessment tools and expand investigations to more cancer types.
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50. |
- Asklund, Thomas, et al.
(author)
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Brain tumors in Sweden : Data from a population-based registry 1999-2012
- 2015
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In: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 54:3, s. 377-384
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Journal article (peer-reviewed)abstract
- Background. The Swedish brain tumor registry has, since it was launched in 1999, provided significant amounts of data on histopathological diagnoses and on important aspects of surgical and medical management of these patients. The purpose is mainly quality control, but also as a resource for research.Methods. Three Swedish healthcare regions, constituting 40% of the Swedish population, have had an almost complete registration. The following parameters are registered: diagnosis according to SNOMED/WHO classification, symptoms, performance status, pre- and postoperative radiology, tumor size and localization, extent of surgery and occurrence of postoperative complications, postoperative treatment, such as radiotherapy and/or chemotherapy, other treatments, complications and toxicity, occurrence of reoperation/s, participation in clinical trials, multidisciplinary conferences and availability of a contact nurse.Results. Surgical radicality has been essentially constant, whereas the use of early (within 72 hours) postoperative CT and MRI has increased, especially for high-grade glioma, which is a reflection of quality of surgery. Survival of patients with high-grade glioma has increased, especially in the age group 60-69. Patients aged 18-39 years had a five-year survival of 40%. Waiting times for the pathological report has been slightly prolonged. Geographical differences do exist for some of the variables.Conclusion. Population-based registration is valuable for assessment of clinical management, which could have impact on patient care. As a result of short survival and/or the propensity to affect cognitive functions this patient group has considerable difficulties to make their voices heard in society. We therefore believe that a report like the present one can contribute to the spread of knowledge and increase the awareness for this patient group among caregivers and policy makers.
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