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11.
  • Dreifaldt, Ann Charlotte, 1964- (författare)
  • Epidemiological aspects on malignant diseases in childhood
  • 2006
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>The trends of malignant diseases in children aged 0 to 14 years, reported to the Swedish Cancer Registry 1960–1998 (n=9 298) were analyzed. The most common diagnoses were leukemia, 29.7%, tumors of the central nervous system (CNS), 27.6%, and lymphomas, 10.2%. The average annual incidence rate of childhood malignant diseases 1990–1998 was 16.19/100 000 person-years. Average annual change in incidence rate of all childhood cancer was +1.01% (95% confidence interval (CI)=0.80-1.22). Statistically significant increase was seen for leukemia +0.85% (95% CI=0.42–1.28), lymphomas +1.87% (95% CI=1.17–2.58), CNS tumors +1.45% (95% CI=1.02–1.88), sympathetic nervous system tumors +1.61% (95% CI=0.79–2.44), hepatic tumors +2.62% (95% CI=2.02–3.21), and germ cell and gonadal tumors +1.21% (95% CI=0.23–2.19).</p> <p>Children are exposed to persistent organic pollutants (POPs) during fetal life and breast-feeding. In a case-control study including cases of childhood cancer reported to the Cancer Registry 1988–1991 (n=962) we used breastfeeding duration as a surrogate for exposure to POPs. One matched control per case was used. Information on breast-feeding, vaccinations and chronic illness was collected from copies of the children’s Child Health Center records.</p> <p>Overall, breast-feeding did not affect the risk of childhood cancer, OR=1.0 (95% CI=0.7–1.3) using breast-feeding up to one month as reference. For non-Hodgkin lymphoma (NHL) OR for breast-feeding for &gt;1 month yielded OR=5.0 (95% CI=1.1–23).</p> <p>No association was seen between preschool vaccinations and childhood cancer except for lymphomas and measles/measles-mumps-rubella vaccination, OR=0.2 (95% CI=0.1–0.6). Increased risk of all cancer was found for congenital malformations, OR=1.7 (95% CI=0.97–2.9), especially of leukemia, OR=3.0 (95% CI=1.5–5.8). Children with disorders of brain function had an increased risk of all cancer, OR=6.0 (95% CI=1.3–27), especially of brain tumors, OR=10 (95% CI=1.3–78).</p> <p>A childhood population expected to be more exposed to POPs is children of fishermen. In a register-based study, the cancer incidence rates in a cohort of fishermen children (at age 0-19 years) were compared to the rates of referent children. A modestly increased incidence rate ratio (IRR) of childhood cancer was found, IRR=1.38 (95% CI=0.96–2.00) and an increased IRR for acute lymphoid leukemia, IRR=2.65 (95% CI=1.005–6.97). In west coast fishermen children, an increased IRR was observed for NHL, IRR=3.19 (95% CI=0.98–10.4).</p>
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12.
  • Isacsson, Ulf (författare)
  • Comparative treatment planning in external radiotherapy of malignant tumours : Potential gains using protons
  • 1998
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • <p>It is well known that protons have physical characteristics superior to conventional radiation qualities in external beam radiotherapy. The primary aim of this work is to determine if the physical advantages also may lead to clinical advantages. A second aim is to evaluate the treatment planning algorithms incorporated into a 3D treatment planning system, used in the prediction, Helax-TMS<sup>TM</sup>. The potential benefits of using protons instead of conventional radiation qualities is evaluated by comparing treatment plans. Dose-response models of tumour control probability (TCP) and normal tissue complication probability (NTCP) were used to predict the treatment outcome for the different plans. Uncertainties in the results were studied in sensitivity analyses.</p><p>Comparative studies were performed in four different tumour types, locally advanced rectal cancer, a paraspinal tumour, oesophageal cancer and left-sided node-positive breast cancer. Advantages with protons were seen in all cases, but the advantages were of different size.</p><p>Proton therapy in patients with oesophageal carcinoma increases the TCP from 6 to 49% if a risk of 1% in the spinal cord and a total NTCP for the two lungs equivalent to a one-sided pulmectomy is allowed. This gain is relatively insensitive to variations, within reasonable limits, in the dose-response parameters.</p><p>Proton therapy reduces the risk for cardiac mortality and radiation pneumonitis to almost zero when treating node-positive left-sided breast cancer after breast-conserving surgery.</p><p>The evaluation of the treatment planning algorithms shows that pencil kernel algorithms are required in order to accurately calculate dose distributions in heterogeneous patient volumes. The scattering phenomenon in the vicinity of interfaces between different materials is modelled. The magnitude of the effect is underestimated (less than 1%) due to the inherent approximations.</p>
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13.
  • Stattin, Pär, et al. (författare)
  • Surveillance and deferred treatment for localized prostate cancer : Population based study in the National Prostate Cancer Register of Sweden
  • 2008
  • Ingår i: Journal of Urology. - Baltimore : Williams and Wilkins. - 0022-5347 .- 1527-3792. ; 180:6, s. 2423-2430
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>PURPOSE: To what extent active surveillance and deferred treatment for localized risk prostate cancer are used is unclear. We assessed the use of surveillance and of deferred treatment in a population based, nationwide cohort in Sweden.</p> <p>MATERIALS AND METHODS: In the National Prostate Cancer Register of Sweden, with a 98% coverage vs the compulsory Swedish Cancer Registry, we identified 8,304 incident cases of prostate cancer in 1997 to 2002 with age younger than 70 years, clinical local stage T1 or 2, N0 or Nx, M0 or Mx and serum prostate specific antigen less than 20 ng/ml. Data were extracted from medical charts for 7,782 of these men (94%) at a median of 4 years after diagnosis.</p> <p>RESULTS: Primary treatment was surveillance for 2,065 men (26%), radical prostatectomy for 3,722 (48%), radiotherapy for 1,632 (21%) and hormonal treatment for 363 (5%). Men on surveillance had lower local tumor stage, grade and prostate specific antigen, and were older than those who received active primary treatment (p &lt;0.001). After a median surveillance of 4 years 711 men (34%) on surveillance had received deferred treatment, which was radical prostatectomy for 279 (39%), radiotherapy for 212 (30%) and hormonal treatment for 220 (30%).</p> <p>CONCLUSIONS: Surveillance was a common treatment for patients younger than 70 years with localized prostate cancer in Sweden in 1997 to 2002, 26% of men with localized prostate cancer started surveillance and after a median followup of 4 years, 66% of these men remained on surveillance.</p>
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14.
  • Planck, Maria (författare)
  • Hereditary Nonpolyposis Colorectal Cancer - Molecular Genetics and Biology of Associated Tumors
  • 2002
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Popular Abstract in Swedish Cancerförekomst i familjen är en riskfaktor för flera vanliga cancerformer. Såväl ärftlig (<i>hereditär</i>) som icke-ärftlig (<i>sporadisk</i>) cancer är resultatet av en ansamling av förändringar (<i>mutationer</i>) i gener vars normala funktion är att reglera cellernas delning, tillväxt och mognad. Vid ärftlig cancer finns den första erforderliga mutationen i kroppens alla celler från födseln, medan de genetiska förändringarna vid sporadisk cancer uppkommit endast i tumörcellerna (<i>somatiska mutationer</i>). <i>HNPCC</i> Syndromet <i>hereditär nonpolyposis kolorektal cancer (HNPCC)</i> betecknar inte (som namnet antyder) en viss cancerform, utan en ärftlig benägenhet att utveckla flera cancertyper, framför allt tjock- och ändtarmscancer (<i>kolorektal cancer</i>) samt livmodercancer, men även cancer i magsäck, tunntarm, äggstockar, urinvägar, hjärna och hud. HNPCC drabbar cirka en av tusen individer och är därigenom ett av de vanligaste ärftliga cancerpredisponerande tillstånd man känner till. Orsaken är en ärftlig mutation i någon av flera <i>DNA-reparationsgener</i>, vanligen <i>MLH1</i> eller <i>MSH2</i>. DNA-reparationsgenerna känner normalt igen och reparerar skador som uppstår i cellernas DNA och förhindrar därmed att somatiska mutationer består och ger upphov till cancer. Defekt DNA-reparation orsakar en genetisk instabilitet, som i sin tur leder till att somatiska mutationer lättare ansamlas och påskyndar cancerutvecklingen. Syndromet ärvs <i>dominant</i>, vilket innebär att barn och syskon till drabbade individer löper 50% risk att bära samma genetiska defekt. <i>Vilka mutationer och gener är inblandade i sydsvenska HNPCC-familjer?</i> I syfte att identifiera HNPCC-familjer och kartlägga ärftliga mutationer i södra Sverige studerade vi generna <i>MLH1</i> och <i>MSH2</i> i sexton familjer med misstänkt HNPCC. För att undersöka betydelsen av nya HNPCC-associerade gener, analyserade vi ytterligare en DNA-reparationsgen, <i>MSH6</i>, i vilken ärftliga mutationer tidigare endast hittats i två japanska familjer. Vi fann sju olika HNPCC-orsakande mutationer, spridda över de tre generna <i>MLH1, MSH2,</i> och <i>MSH6</i>. Även om <i>MSH6</i>-mutation är en mindre vanlig orsak till HNPCC är analys av <i>MSH6</i>-genen således av värde i familjer där man ej funnit någon mutation i <i>MLH1</i> eller <i>MSH2</i>. <i>Hur vanligt är defekt DNA-reparation?</i> Vi har undersökt betydelsen av defekt DNA-reparation för uppkomst av ändtarmscancer, tunntarmscancer samt hos patienter som utvecklat både livmodercancer och kolorektal cancer. Sporadisk kolorektal cancer drabbar ändtarmen i en tredjedel av fallen medan HNPCC-tumörer mera sällan uppkommer där. För att studera DNA-reparationsgenernas roll i ändtarmscancer analyserade vi förekomsten av <i>mikrosatellitinstabilitet</i> och ärftlig mutation i <i>MLH1, MSH2</i> och <i>MSH6</i> i 165 ändtarmscancrar. Mikrosatellitinstabilitet uppkommer i tumörer med defekt DNA-reparation och innebär en förkortning av sekvenser som består av likadana DNA-byggstenar upprepade många gånger efter varandra. Sådana repeterade DNA-sekvenser (<i>mikrosatelliter</i>) drabbas ofta av den typ av skador som <i>MLH1, MSH2</i> och <i>MSH6</i> normalt reparerar. Vi fann att mikrosatellitinstabilitet i ändtarmstumörer är ovanligt (3/165) men starkt indikerar HNPCC-mutation, vilket påvisades hos alla de tre patienter som hade mikrosatellitinstabilitet i tumörerna. Trots att individer med HNPCC löper en 100-faldigt ökad risk att drabbas av cancer i tunntarmen, utgör denna ovanliga cancerform endast en liten andel av HNPCC-tumörerna och är ofullständigt studerad. Vi undersökte 70 tunntarmscancrar avseende DNA-reparations-defekter och fann mikrosatellitinstabilitet och/eller förlust av MLH1 eller MSH2 i ungefär samma frekvens som i tjocktarmscancer (13/70). Detta tyder på en liknande roll för DNA-reparationsgenerna i tunntarmscancer och visar att analys av mikrosatellitinstabilitet är av värde vid misstanke om HNPCC-associerad tumör i tunntarmen. Den vanligaste icke-kolorektala cancerformen vid HNPCC är livmodercancer. Kvinnor med HNPCC löper således hög risk att drabbas av både kolorektal cancer och livmodercancer. Från det svenska cancerregistret identifierade vi individer som utvecklat båda dessa cancerformer i ung ålder och undersökte tumörerna avseende mikrosatellitinstabilitet och förlust av MLH1, MSH2 och MSH6. Identisk förlust i båda tumörerna från samma individ är förenligt med ärftlig mutation i respektive DNA-reparationsgen och demonstrerades hos nästan hälften av dessa individer. Således finns det starka skäl att misstänka HNPCC hos patienter som drabbats av både livmodercancer och kolorektal cancer i ung ålder. <i>Hur orsakar defekt DNA-reparation cancer?</i> Den typ av skador som DNA-reparationsgenerna normalt reparerar drabbar främst repeterade DNA-sekvenser. Somatiska mutationer i gener som innehåller repeterade sekvenser och samtidigt har en cellreglerande funktion utgör en möjlig mekanism för tumöruppkomst vid defekt DNA-reparation. Vi undersökte mönstret av somatiska mutationer i olika sådana gener, dels i olika tumörer från en stor HNPCC-familj och dels i olika delar av en och samma HNPCC-tumör. Vi fann att dessa somatiska mutationer varierade både mellan olika tumörer med samma bakomliggande HNPCC-mutation och inom en och samma tumör. Denna variabilitet indikerar att ingen av de undersökta generna i sig är nödvändig för canceruppkomst utan att utvecklingen av en HNPCC-tumör snarare kräver en ansamling av ett flertal sådana mutationer. Sammanfattningsvis har vi i dessa studier · identifierat nya HNPCC-orsakande mutationer, · kartlagt frekvensen defekt DNA-reparation i ändtarmscancer och tunntarmscancer, · påvisat hög frekvens mikrosatellitinstabilitet och förlust av DNA-reparationsproteiner hos kvinnor som utvecklat både kolorektal cancer och livmodercancer samt · demonstrerat såväl intra- som intertumörheterogenitet av somatiska mutationer i cancerassocierade gener med repeterade sekvenser. Studierna bidrar därmed till en ökad förståelse för hur defekt DNA-reparation orsakar cancer och hur HNPCC-orsakade tumörer utvecklas.
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15.
  • Alfonzo, Emilia, et al. (författare)
  • No survival difference between robotic and open radical hysterectomy for women with early-stage cervical cancer: results from a nationwide population-based cohort study
  • 2019
  • Ingår i: European Journal of Cancer. - 0959-8049. ; 116, s. 169-177
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The aim of the study was to compare overall survival (OS) and disease-free survival (DFS) after open and robotic radical hysterectomy for early-stage cervical cancer. Patients and methods: This was a nationwide population-based cohort study on all women with cervical cancer stage IA1-IB of squamous, adenocarcinoma or adenosquamous histological subtypes, from January 2011 to December 2017, for whom radical hysterectomy was performed. The Swedish Quality Register of Gynaecologic Cancer was used for identification. To ensure quality and conformity of data and to disclose patients not yet registered, hospital registries were reviewed and validated. Cox and propensity score regression analysis and univariable and multivariable regression analysis were performed in regard to OS and DFS. Results: There were 864 women (236 open and 628 robotic) included in the study. The 5-year OS was 92% and 94% and DFS was 84% and 88% for the open and robotic cohorts, respectively. The recurrence pattern was similar in both groups. Using propensity score analysis and matched cohorts of 232 women in each surgical group, no significant differences were seen in survival: 5-year OS of 92% in both groups (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.50–2.01) and DFS of 85% vs 84% in the open and robotic cohort, respectively (HR, 1.08; 95% CI, 0.66–1.78). In univariable and multivariable analysis with OS as the end-point, no significant factors were found, and in regard to DFS, tumour size (p < 0.001) and grade 3 (p = 0.02) were found as independent significant risk factors. Conclusion: In a complete nationwide population-based cohort, where radical hysterectomy for early-stage cervical cancer is highly centralised, neither long-term survival nor pattern of recurrence differed significantly between open and robotic surgery.
16.
  • Ramos-Casals, Manel, et al. (författare)
  • Sicca/Sjögren's syndrome triggered by PD-1/PD-L1 checkpoint inhibitors. Data from the International Immunocancer Registry (ICIR)
  • 2019
  • Ingår i: Clinical and Experimental Rheumatology. - Pacini. - 1593-098X. ; 37, s. 114-122
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To analyse the worldwide occurrence of sicca/Sjögren's (SS) syndrome associated with the use of immune checkpoint inhibitors (ICI) in patients with cancer. Methods. The ImmunoCancer International Registry (ICIR) is a Big Data- Sharing multidisciplinary network composed by 40 specialists in Rheumatology, Internal Medicine, Immunology and Oncology from 18 countries focused on the clinical and basic research of the immune-related adverse events (irAEs) related to cancer immunotherapies. For this study, patients who were investigated for a clinical suspicion of SS after being exposed to ICI were included. Results. We identified 26 patients (11 women and 15 men, with a mean age at diagnosis of 63.57 years). Underlying cancer included lung (n=12), renal (n=7), melanoma (n=4), and other (n=3) neoplasia. Cancer immunotherapies consisted of monotherapy (77%) and combined regimens (23%). In those patients receiving monotherapy, all patients were treated with PD-1/PD-L1 inhibitors (nivolumab in 9, pembrolizumab in 7 and durvalumab in 4); no cases associated with CTLA-4 inhibitors were identified. The main SS-related features consisted of dry mouth in 25 (96%) patients, dry eye in 17 (65%), abnormal ocular tests in 10/16 (62%) and abnormal oral diagnostic tests in 12/14 (86%) patients. Minor salivary gland biopsy was carried out in 15 patients: histopathological findings consisted of mild chronic sialadenitis in 8 (53%) patients and focal lymphocytic sialadenitis in the remaining 7 (47%); a focus score was measured in 5 of the 6 patients (mean of 1.8, range 1-4). Immunological markers included positive ANA in 13/25 (52%), anti-Ro/ SS-A in 5/25 (20%), RF in 2/22 (9%), anti-La/SS-B in 2/25 (8%), low C3/C4 levels in 1/17 (6%) and positive cryoglobulins in 1/10 (10%). Classification criteria for SS were fulfilled by 10 (62%) out of 16 patients in whom the two key classificatory features were carried out. Among the 26 patients, there were only 3 (11%) who presented exclusively with sicca syndrome without organ-specific autoimmune manifestations. Therapeutic management included measures directed to treat sicca symptoms and therapies against autoimmune-mediated manifestations (glucocorticoids in 42%, second/ third-line therapies in 31%); therapeutic response for systemic features was observed in 8/11 (73%). No patient died due to autoimmune involvement. Conclusion. Patients with Sjögren's syndrome triggered by ICI display a very specific profile different from that reported in idiopathic primary SS, including more frequent occurrence in men, a higher mean age, a predominant immunonegative serological profile, and a notable development of organ-specific autoimmune involvement in spite of the poor immunological profile. The close association found between sicca/Sjögren's syndrome and primarily PD-1 blockade requires further specific investigation. © COPYRIGHT CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2019.
17.
  • Adolfsson, Jan, et al. (författare)
  • Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005 : Data from the national prostate cancer register in Sweden
  • 2007
  • Ingår i: Scandinavian Journal of Urology and Nephrology. - Stockholm : Taylor & Francis. - 0036-5599 .- 1651-2065. ; 41:6, s. 456-477
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><em>Objective.</em> The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. <em>Material and methods.</em> Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. <em>Results.</em> In total, 72 028 patients were registered, comprising &gt;97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of &gt;100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score ≤6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of &lt;20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged ≥75 years than in those aged &lt;75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. <em>Conclusions.</em> All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer</p>
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18.
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19.
  • Anderzén-Carlsson, Agneta, 1966- (författare)
  • Att hantera rädsla hos barn med cancer
  • 2008
  • Ingår i: Onkologi i Sverige. - 1653-1582. ; 4:6, s. 14-20
  • Tidskriftsartikel (populärvet., debatt m.m.)
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20.
  • Anderzén-Carlsson, Agneta, 1966-, et al. (författare)
  • Embodied suffering : experiences of fear in adolescent girls with cancer
  • 2008
  • Ingår i: Journal of Child Health Care. - London : Sage. - 1367-4935 .- 1741-2889. ; 12:2, s. 129-143
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Previously, fear in adolescents with cancer has been sparsely described from an emic perspective. The aim of this study was to illuminate fear in adolescents with personal experience of cancer. The participants were six adolescent girls between the age of 14 and 16 years who were no longer under active treatment for cancer but still went for regular check-ups. Open interviews were conducted. Data were analysed according to the phenomenological hermeneutic method. In the result one main theme was identified: `an embodied fear — a threat to the personal self'. This theme was built up by three separate but intertwined themes: `experiencing fear related to the physical body', `experiencing existential fear' and `experiencing fear related to the social self'. In the comprehensive understanding the fear was interpreted from youth cultural aspects as well as a holistic perspective. The importance of professionals taking the whole person and their situation into account when meeting the fear is underlined.</p>
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