Background: Radiotherapy (RT) after breast conserving surgery (BCS) for ductal carcinoma in situ (DCIS) reduces the relative ipsilateral breast event (IBE) risk by 50%. The DCISionRT® test estimates IBE risk in DCIS women treated with... more
Background: Radiotherapy (RT) after breast conserving surgery (BCS) for ductal carcinoma in situ (DCIS) reduces the relative ipsilateral breast event (IBE) risk by 50%. The DCISionRT® test estimates IBE risk in DCIS women treated with BCS, and RT benefit. The test has been validated in five cohorts, including the SweDCIS randomized trial. Swedish national guidelines define low-risk DCIS using clinicopathology criteria. Methods: We determined the number of women irradiated per IBE prevented and treatment-costs based on 10-year outcomes from the SweDCIS trial. Four strategies were compared: no RT (Strategy 1); RT for all (Strategy 2), RT for DCISionRT Elevated Risk only (Strategy 3); Swedish DCIS Guidelines, omit RT for low-risk (Strategy 4). In SweDCIS, women were randomised to RT or not after BCS, 1988-2000 (n=1046). Data for DCISionRT biomarkers (PR, HER2, Ki67, FOXA1, p16/INK4A, SIAH2, COX2) and clinical factors (age, tumor size, margin, palpability) were available for 504 women w...
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Purpose: The effect of postoperative radiotherapy (RT) based on the immune phenotype of tumor-infiltrating lymphocytes (TILs) has not been investigated. The purpose of this study was to analyze how the balance between CD8+ T cells and T... more
Purpose: The effect of postoperative radiotherapy (RT) based on the immune phenotype of tumor-infiltrating lymphocytes (TILs) has not been investigated. The purpose of this study was to analyze how the balance between CD8+ T cells and T regulatory cells (FOXP3+), which have opposite effects on the anti-tumoral defense, affects the risk of ipsilateral breast tumor recurrence (IBTR) and of any recurrence as well as the interaction with RT in a large randomized RT trial. Methods: In the SweBCG91RT trial, patients with breast cancer stage I and II were randomized to breast conserving surgery (BCS) and postoperative RT or BCS only and followed for a median time of 15.2 years. Tumor blocks were retrieved and stromal TILs were assessed through hematoxylin-eosin stained slides. CD8+ T cells and T regulatory cells were evaluated through staining for CD8 and FOXP3 and the percentage of stroma occupied by CD8+ T cells and T regulatory cells respectively was then calculated. Cutoffs at 5% and 2...
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Objective Oral leukoplakia (OL) presents as a white lesion of the oral mucosa and is not typically associated with the sensation of pain. OL should be surgically removed when possible because it is considered a potentially malignant oral... more
Objective Oral leukoplakia (OL) presents as a white lesion of the oral mucosa and is not typically associated with the sensation of pain. OL should be surgically removed when possible because it is considered a potentially malignant oral disorder (PMOD). This study assessed the pain sensations experienced by patients in association with the occurrence and surgical treatment of OL. Methods Inclusion criteria were: a clinical diagnosis of OL; biopsy excision; and observation for at least 12 months in the ORA-LEU-CAN study. At the first visit, all the patients were asked about the occurrence of symptoms within the lesion. Ninety-four subjects were assessed over a period of 1 year. All patients underwent complete removal of OL. The patient cohort was divided into three sub-groups: (i) no pain before excision and at the 1-year follow-up; (ii) pain before excision; and (iii) pain at the 1-year follow-up. Results Overall, pain was reported by 21.3% of the patients at the study start wherea...
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Background: Although preclinical studies have indicated that stroma cells can modulate the radiosensitivity of tumor cells, non-leukocytic stroma cells have not yet been explored as potential predictive markers for radiotherapy (RT)... more
Background: Although preclinical studies have indicated that stroma cells can modulate the radiosensitivity of tumor cells, non-leukocytic stroma cells have not yet been explored as potential predictive markers for radiotherapy (RT) through systematic analyses of clinical samples. Platelet-derived growth factor receptor beta (PDGFRb) is a key regulator of fibroblasts, pericytes and smooth muscle cells. A high expression of PDGFRb in tumor-associated stroma has previously been associated with worse recurrence free and breast cancer specific survival as well as reduced tamoxifen sensitivity in invasive breast cancer. Purpose: To analyze the prognostic and predictive impact of stromal PDGFRb regarding ipsilateral breast tumor recurrence (IBTR) and any recurrence in a large randomized RT trial. Methods: Stromal PDGFRb expression was assessed by immunohistochemical staining of tissue microarrays (TMAs) with 958 tumors from the SweBCG91RT trial (Swedish Breast Cancer Group 91 Radiotherapy...
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Prediction of radiotherapy (RT) benefit after breast-conserving surgery (BCS) for DCIS is crucial. The aim was to validate a biosignature, DCISionRT®, in the SweDCIS randomized trial. Women were randomly assigned to RT or not after BCS,... more
Prediction of radiotherapy (RT) benefit after breast-conserving surgery (BCS) for DCIS is crucial. The aim was to validate a biosignature, DCISionRT®, in the SweDCIS randomized trial. Women were randomly assigned to RT or not after BCS, between 1987 and 2000. Tumor blocks were collected, and slides were sent to PreludeDxTM for testing. In 504 women with complete data and negative margins, DCISionRT divided 52% women into Elevated (DS > 3) and 48% in Low (DS ≤ 3) Risk groups. In the Elevated Risk group, RT significantly decreased relative 10-year ipsilateral total recurrence (TotBE) and 10-year ipsilateral invasive recurrence (InvBE) rates, HR 0.32 and HR 0.24, with absolute decreases of 15.5% and 9.3%. In the Low Risk group, there were no significant risk differences observed with radiotherapy. Using a cutoff of DS > 3.0, the test was not predictive for RT benefit (p = 0.093); however, above DS > 2.8 RT benefit was greater for InvBE (interaction p = 0.038). Recurrences at 1...
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AIM The first Swedish National Guidelines for Ovarian Cancer (NGOC) were published in 2012. We aimed to evaluate surgical outcomes and survival in patients with stage IIIC-IV disease, before and after the NGOC implementation. METHOD Women... more
AIM The first Swedish National Guidelines for Ovarian Cancer (NGOC) were published in 2012. We aimed to evaluate surgical outcomes and survival in patients with stage IIIC-IV disease, before and after the NGOC implementation. METHOD Women with primary epithelial ovarian cancer, FIGO stage IIIC-IV, registered in the Swedish Quality Registry for Gynecologic Cancer 2008-2011 and 2013-2016 were included. Surgical outcomes were analyzed, including frequency of complete cytoreduction (R0). Relative survival (RS) and excess mortality rate ratios (EMRRs) were computed as measures of survival. Univariable and multivariable regression (Poisson) were calculated. RESULTS In total, 3728 women were identified, 1746 before and 1982 after NGOC. After adjusting for age and stage, survival was improved 2013-2016 vs. 2008-2011 (EMRR 0.89; 95%CI:0.82-0.96, p < 0.05). For women undergoing primary debulking surgery (PDS), R0 frequency (28.9% vs. 53.3%; p < 0.001) and 5-year RS (29.6% (95%CI:26.8-32.8) vs. 37.4% (95%CI:33.6-41.7)) were increased, but fewer patients (58% vs. 44%, p < 0.001) underwent PDS after NGOC implementation. Median survival for the PDS cohort increased from 35 months (95%CI,32.8-39.2) to 43 months (95%CI,40.9-46.4). In the neoadjuvant chemotherapy (NACT) + interval debulking surgery (IDS) cohort, R0 increased (36.8% to 50.1%, p < 0.001), but not 5-year RS (17.5% vs. 20.7%, ns). Compared to PDS, the EMRR was 1.32 (95%CI,1.19-1.47, p < 0.001) for NACT+IDS and 3.00 (95%CI,2.66-3.38, p < 0.001) for chemotherapy alone. In multivariable analyses, PDS, R0, age ≤ 70 years, and stage IIIC were found to be independent factors for improved RS. CONCLUSION Implementation of the first National Guidelines for Ovarian Cancer improved relative survival in advanced ovarian cancer.
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OBJECTIVE Vulvar cancer affects mainly elderly women and with an ageing population the incidence has increased. We explored the primary treatment patterns and relative survival of patients with vulvar squamous cell carcinoma (VSCC) by... more
OBJECTIVE Vulvar cancer affects mainly elderly women and with an ageing population the incidence has increased. We explored the primary treatment patterns and relative survival of patients with vulvar squamous cell carcinoma (VSCC) by stage and age-group. METHODS A population-based nationwide study on women diagnosed with VSCC between 2012 and 2016 and registered in the Swedish Quality Registry for Gynecologic Cancer (SQRGC). Main outcome was 5-year relative survival (RS) estimated by the Pohar Perme method. The relative risk of excess mortality (EMRR) between different groups was analyzed by Poisson regression. The age-standardized relative survival (AS-RS) was estimated for the total cohort. RESULTS Median follow-up time was 41 months. The study population included 657 women; 33% were ≥ 80 years old. FIGO stage I was most common (55%). Primary surgery was performed in 96% stage I, 65% stage II, 80% stage III and 28% stage IV. In women ≥80 years, exploration of the groins and chemoradiotherapy was less often performed. They also received lower mean doses of radiation than younger women. The 5-year AS-RS was 74%. 5-year RS was 84% for stage I, 60% for stage II, 54% for stage III and 35% for stage IV. The EMRR for women ≥80 years compared with women <60 years was 4.3 (p < 0.001); 4.9 (p < 0.001) for stages I-II and 3.5(p = 0.007) for stage III. CONCLUSIONS In general, primary treatment of patients with vulvar squamous cell carcinoma in Sweden adhered to guidelines. Areas of improvement include treatment for stage II and for the very old.
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Research Interests: Breast Cancer, Medicine, Parameter estimation, Multivariate Analysis, Complication, and 15 moreHumans, Autoimmune Disease, Blood Pressure, Female, Clinical Sciences, Aged, Middle Aged, Adult, Prognosis, Genetic variation, Hormone Therapy, Individual Difference, Adverse effects, Breast Neoplasms, and multivariate analyses
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Women with BRCA variants have a high lifetime risk of developing breast and ovarian cancer. The aim of this study was to investigate the standard incidence ratios (SIR) for breast and ovarian cancer and standard mortality ratios (SMR) in... more
Women with BRCA variants have a high lifetime risk of developing breast and ovarian cancer. The aim of this study was to investigate the standard incidence ratios (SIR) for breast and ovarian cancer and standard mortality ratios (SMR) in a population-based cohort of women in Western Sweden, under surveillance and after risk reducing surgery. Women who tested positive for a BRCA variant between 1995–2016 (n = 489) were prospectively registered and followed up for cancer incidence, risk reducing surgery and mortality. The Swedish Cancer Register was used to compare breast and ovarian cancer incidence and mortality with and without risk reducing surgery for women with BRCA variants in comparison to women in the general population. SIR for breast cancer under surveillance until risk-reducing mastectomy (RRM) was 14.0 (95% CI 9.42–20.7) and decreased to 1.93 (95% CI 0.48–7.7) after RRM. The SIR for ovarian cancer was 124.6 (95% CI 59.4–261.3) under surveillance until risk reducing salpin...
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Background: Organ transplant recipients (OTRs) have a very high risk of developing cutaneous squamous cell carcinoma (cSCC). Immunosuppressed OTRs may have a higher proportion of poorly differentiated cSCC than non-OTRs. Objectives: The... more
Background: Organ transplant recipients (OTRs) have a very high risk of developing cutaneous squamous cell carcinoma (cSCC). Immunosuppressed OTRs may have a higher proportion of poorly differentiated cSCC than non-OTRs. Objectives: The aim of this study was to investigate the degree of differentiation of cSCCs in OTRs compared with immunocompetent individuals. Patients/Methods: Data from the Swedish Cancer Registry were crosschecked with data from the Transplant registry of the Transplant Institute at Sahlgrenska University Hospital in Gothenburg, Sweden. All OTRs with a diagnosis of cSCC, basosquamous carcinoma, and/or cSCC in situ established at the Department of Dermatology, Sahlgrenska University Hospital, during 2002-2015 were included. The control group consisted of non-OTRs with the same diagnoses during the same time period. Results: During 2002-2015, 82 OTRs diagnosed with 515 tumors and 883 non-OTRs with 1,247 tumorswere included. OTRs developed 0.47 tumors/year vs 0.10 t...
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Concurrent chemoradiotherapy is the mainstay treatment for NSCLC stage III disease. To investigate whether radiation dose escalation based on individual normal tissue constraints can improve outcome, the Swedish lung cancer study group... more
Concurrent chemoradiotherapy is the mainstay treatment for NSCLC stage III disease. To investigate whether radiation dose escalation based on individual normal tissue constraints can improve outcome, the Swedish lung cancer study group launched this randomized phase II trial. NSCLC patients with stage III disease, good performance status (0-1) and adequate lung function (FEV1 > 1.0 L and CO diffusion capacity > 40%) received three cycles of cisplatin (75 mg/m day 1) and vinorelbine (25 mg/m day 1 and 8) every third week. Radiotherapy started concurrently with the second cycle, with either 2 Gy daily, 5 days a week, to 68 Gy (A) or escalated therapy (B) based on constraints to the spinal cord, esophagus and lungs up to 84 Gy by adding an extra fraction of 2 Gy per week. A pre-planned safety analysis revealed excessive toxicity and decreased survival in the escalated arm, and the study was stopped. Thirty-six patients were included during 2011-2013 (56% male, 78% with adenocarci...
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Substantial evidence links exposure to moderate or high doses of ionising radiation, particularly in childhood, with increased risk of leukaemia. The association of leukaemia with exposure to low-dose (<100 mSv) radiation is less... more
Substantial evidence links exposure to moderate or high doses of ionising radiation, particularly in childhood, with increased risk of leukaemia. The association of leukaemia with exposure to low-dose (<100 mSv) radiation is less certain, although this is the dose range most relevant to the general population. We aimed to estimate the risk of leukaemia associated with low-dose radiation exposure in childhood (age <21 years). In this analysis of historical cohort studies, we pooled eligible cohorts reported up to June 30, 2014. We evaluated leukaemia and myeloid malignancy outcomes in these cohorts with the relevant International Classification of Diseases and International Classification of Diseases for Oncology definitions. The cohorts included had not been treated for malignant disease, had reported at least five cases of the relevant haematopoietic neoplasms, and estimated individual active bone marrow (ABM) doses. We restricted analysis to individuals who were younger than...
Lenalidomide (Len) plus dexamethasone (Dex) is approved for the treatment of relapsed or refractory multiple myeloma (RRMM). It is possible that single-agent Len may be effective as prolonged treatment regimen in RRMM once patients... more
Lenalidomide (Len) plus dexamethasone (Dex) is approved for the treatment of relapsed or refractory multiple myeloma (RRMM). It is possible that single-agent Len may be effective as prolonged treatment regimen in RRMM once patients demonstrate an initial response to Len+Dex induction. Patients with RRMM who responded to first-line Len+Dex in an observational study (NCT01430546) received up to 24 cycles of either Len (25 mg/day) or Len+Dex (25 mg/day and 40 mg/week) as prolonged treatment in a subsequent phase 2 clinical trial (NCT01450215). In the observational study (N = 133), median time to response was 1.7 (range 0.6-9.6) months. A complete response to all treatments received in both studies was observed in 11% of patients; very good partial response and partial response rates were 31% and 38%, respectively. Corresponding response rates in the subgroup of patients who did not enter the phase 2 trial (n = 71) were 3%, 18%, and 39%, respectively. Rates of disease progression at 2 y...
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This study examined whether previously reported results, indicating that prostate-specific antigen (PSA) screening can reduce prostate cancer (PC) mortality regardless of sociodemographic inequality, could be corroborated in an 18 year... more
This study examined whether previously reported results, indicating that prostate-specific antigen (PSA) screening can reduce prostate cancer (PC) mortality regardless of sociodemographic inequality, could be corroborated in an 18 year follow-up. In 1994, 20,000 men aged 50-64 years were randomized from the Göteborg population register to PSA screening or control (1:1) (study ID: ISRCTN54449243). Men in the screening group (n = 9950) were invited for biennial PSA testing up to the median age of 69 years. Prostate biopsy was recommended for men with PSA ≥2.5 ng/ml. Last follow-up was on 31 December 2012. In the screening group, 77% (7647/9950) attended at least once. After 18 years, 1396 men in the screening group and 962 controls had been diagnosed with PC [hazard ratio 1.51, 95% confidence interval (CI) 1.39-1.64]. Cumulative PC mortality was 0.98% (95% CI 0.78-1.22%) in the screening group versus 1.50% (95% CI 1.26-1.79%) in controls, an absolute reduction of 0.52% (95% CI 0.17-0....
Heart transplantation (HTx) has become the standard treatment for patients with end-stage heart disease. We report on the long-term outcome after HTx at our centre and investigate trends in outcome over time. During the period, between... more
Heart transplantation (HTx) has become the standard treatment for patients with end-stage heart disease. We report on the long-term outcome after HTx at our centre and investigate trends in outcome over time. During the period, between 1984 and 2014, a total of 610 HTx procedures were performed in 595 patients (median 48years; IQR 31-57years; range 24days-71years; mean 43years; 75% male) in our institution. Long-term outcome was investigated in the whole cohort, among children (n=76), bridged with mechanical circulatory support (MCS, n=131), re-transplanted (n=17), and concomitant kidney transplantation (n=12). Long-term survival was at 1, 5, 10, 15 and 20years: 86% (95CI 0.83-0.89); 77% (95CI 0.73-0.80); 63% (95CI 0.59-0.68); 48% (95CI 0.43-0.54) and 30% (95CI 0.25-0.36), respectively. The median survival for the whole cohort was 14.1years. Patients transplanted during the most recent time period (2010-2014) had a better survival compared to previous eras, with a 1- and 3-year surv...
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The increased use of diagnostic and therapeutic procedures that involve radiation raises concerns about radiation effects, particularly in children and to the radio-sensitive thyroid gland. Evaluation of relative risk (RR) trends for... more
The increased use of diagnostic and therapeutic procedures that involve radiation raises concerns about radiation effects, particularly in children and to the radio-sensitive thyroid gland. Evaluation of relative risk (RR) trends for thyroid radiation doses <0.2 gray; evidence of a threshold dose; and possible modifiers of the dose-response, e.g., sex, age at exposure, time since exposure. Pooled data from nine cohort studies of childhood external radiation exposure and thyroid cancer with individualized dose estimates, ≥1,000 irradiated subjects or ≥10 thyroid cancer cases, with data limited to individuals receiving doses <0.2 gray. Cohorts included: childhood cancer survivors (n=2); children treated for benign diseases (n=6); and children who survived the atomic bombings in Japan (n=1). There were 252 cases and 2,588,559 person-years in irradiated individuals and 142 cases and 1,865,957 person-years in non-irradiated individuals. There were no interventions. Incident thyroid...
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The aim of the study was to determine survival outcome in patients with serous cancer in the ovary, fallopian tube, peritoneum and of undesignated origin. Nation-wide population-based study of women≥18years with histologically verified... more
The aim of the study was to determine survival outcome in patients with serous cancer in the ovary, fallopian tube, peritoneum and of undesignated origin. Nation-wide population-based study of women≥18years with histologically verified non-uterine serous cancer, included in the Swedish Quality Registry for primary cancer of the ovary, fallopian tube and peritoneum diagnosed 2009-2013. Relative survival (RS) was estimated using the Ederer II method. Simple and multivariable analyses were estimated by Poisson regression models. Of 5627 women identified, 1246 (22%) had borderline tumors and 4381 had malignant tumors. In total, 2359 women had serous cancer; 71% originated in the ovary (OC), 9% in the fallopian tube (FTC), 9% in the peritoneum (PPC) and 11% at an undesignated primary site (UPS). Estimated RS at 5-years was 37%; for FTC 54%, 40% for OC, 34% for PPC and 13% for UPS. In multivariable regression analyses restricted to women who had undergone primary or interval debulking surgery for OC, FTC and PPC, site of origin was not independently associated with survival. Significant associations with worse survival were found for advanced stages (RR 2.63, P&amp;amp;amp;amp;lt;0.001), moderate (RR 1.90, P&amp;amp;amp;amp;lt;0.047) and poor differentiation (RR 2.20, P&amp;amp;amp;amp;lt;0.009), neoadjuvant chemotherapy (RR1.33, P&amp;amp;amp;amp;lt;0.022), residual tumor (RR 2.65, P&amp;amp;amp;amp;lt;0.001) and platinum single (2.34, P&amp;amp;amp;amp;lt;0.001) compared to platinum combination chemotherapy. Survival was poorer for serous cancer at UPS than for ovarian, fallopian tube and peritoneal cancer. Serous cancer at UPS needs to be addressed when reporting and comparing survival rates of ovarian cancer.
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Stereotactic body radiotherapy (SBRT) has been introduced for small lung tumors due to excellent local control and few side effects, even though there are no comparative studies. SPACE (Stereotactic Precision And Conventional radiotherapy... more
Stereotactic body radiotherapy (SBRT) has been introduced for small lung tumors due to excellent local control and few side effects, even though there are no comparative studies. SPACE (Stereotactic Precision And Conventional radiotherapy Evaluation) is the first randomized phase II trial comparing SBRT and conventional fractionated radiotherapy (3DCRT). Patients with stage I medically inoperable NSCLC were randomized to receive SBRT to 66Gy in 3 fractions (one week) or 3DCRT to 70Gy (7weeks). Patients were followed to assess efficacy, toxicity and HRQL. Between 2007 and 2011, 102 patients were randomized. Mean age 74 (57-86), 60% women, the vast majority (92%) had COPD or cardiovascular comorbidity. The SBRT arm included more patients with T2-tumors (p=0.02) and male gender (p=0.35). The median follow-up was 37months with a 1-, 2- and 3-year PFS of: SBRT: 76%, 53%, 42% and 3DCRT: 87%, 54% 42%, HR=0.85 (95% CI 0.52-1.36) with no difference between the groups and no difference in OS (HR=0.75, 95% CI 0.43-1.30). At the end of the study 70% of SBRT patients had not progressed compared to 59% (3DCRT, p=0.26). Toxicity was low with no grade 5 events. Pneumonitis of any grade was observed in 19% (SBRT) and 34% (3DCRT, p=0.26), and esophagitis in 8% and 30% respectively (p=0.006). HRQL was evaluated with the EORTC QLQ 30 and LC14 module and patients treated with 3DCRT experienced worse dyspnea (p=0.01), chest pain (p=0.02) and cough (&amp;amp;amp;amp;amp;amp;gt;10 points difference). There was no difference in PFS and OS between SBRT and conventionally treated patients despite an imbalance of prognostic factors. We observed a tendency of an improved disease control rate in the SBRT group and they experienced better HRQL and less toxicity. SBRT is convenient for patients and should be considered standard treatment for patients with inoperable stage I NSCLC.
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This study focuses on the incidence, treatment, and survival of de novo acute leukemia in a 25-year perspective in western Sweden and Estonia. At the beginning of our study, Estonia was a part of the Eastern bloc with planned economy, but... more
This study focuses on the incidence, treatment, and survival of de novo acute leukemia in a 25-year perspective in western Sweden and Estonia. At the beginning of our study, Estonia was a part of the Eastern bloc with planned economy, but since 1991 it is a member of the European Union and transforming into a market economy. Survival rates have steadily increased in both countries. However, a gap between their survival curves remains. Based on our data, it is difficult to explain the big difference in the 5-year relative survival in favor of western Sweden (55 vs. 22%). In Germany, there was a big difference in overall cancer survival between East and West Germany after the fall of the iron curtain, but today no difference is seen. Differences in survival are probably due to a higher proportion of intense chemotherapy regimens and a higher rate of hematopoietic stem cell transplantations in Sweden. Other important factors might be better supportive care and diagnostics as well as be...
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This study describes the occurrence of renal failure among 1353 newly diagnosed cases of multiple myeloma. Renal function was evaluated by serum creatinine concentration in 1353 cases, 31% of whom had renal failure at the time of... more
This study describes the occurrence of renal failure among 1353 newly diagnosed cases of multiple myeloma. Renal function was evaluated by serum creatinine concentration in 1353 cases, 31% of whom had renal failure at the time of diagnosis. In 1206 cases an estimation of creatinine clearance was made. When renal failure was defined by using creatinine clearance estimation, 49% had renal failure at the time of diagnosis. Renal failure was present in 24% of patients with an M component of IgG-, 31% of IgA- and 100% of IgD-type. 52% of patients with light chain disease had renal failure. The frequency of renal failure was similar in lambda- and kappa-light chain disease. Patients with a high excretion of Bence Jones protein in the urine (&gt; 10 g/24 h) had renal failure significantly more often than patients with lower excretion. Renal failure was related to advanced disease; 41% of patients with stage III (Durie-Salmon) disease had renal failure. Renal failure was found in 45% of patients with hypercalcaemia. When estimated creatinine clearance was used as a predictor of renal function, the same trends were found as mentioned above. In addition, the proportion of patients with renal failure was found to increase with advancing age.
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High-dose therapy has become a common treatment for myeloma. The objectives of this study were to estimate in a prospective, population-based setting the impact on survival of high-dose therapy in newly diagnosed, symptomatic patients... more
High-dose therapy has become a common treatment for myeloma. The objectives of this study were to estimate in a prospective, population-based setting the impact on survival of high-dose therapy in newly diagnosed, symptomatic patients less than 60 years old and to compare the results with those of conventionally treated historic controls. The prospective population comprised 348 patients. Of these, 274 were treated according to a specified intensive-therapy protocol (Nordic Myeloma Study Group [NMSG] #5/94) and constituted the intensive-therapy group. The historic population consisted of 313 patients identified from 5 previous population-based Nordic studies. Of these, 274 fulfilled the eligibility criteria for high-dose therapy stated in NMSG #5/94 and constituted the control group. The expected numbers of patients in the prospective population and the historic population were 450 and 410, respectively, estimated from previously established data on the incidence in this population and the population base for each study. Survival was prolonged in the intensive-therapy group compared with the control group (risk ratio for the control group 1.62; 95% confidence interval 1.22-2.15; P =.001). These groups represented more than 60% of the expected number of patients. When survival for all the registered patients in the 2 populations was compared, representing more than 75% of the expected number of patients, the advantage for the prospective population persisted (risk ratio for the historic population 1.46; 95% confidence interval 1.14-1.86; P =. 002). These results indicate that the introduction of high-dose therapy for newly diagnosed myeloma has resulted in prolonged survival for the total patient population aged less than 60 years. (Blood. 2000; 95:7-11)
Research Interests: Survival Analysis, Dexamethasone, Humans, Female, Blood, and 14 moreMultiple Myeloma, Male, Confidence intervals, Clinical Sciences, Middle Aged, Doxorubicin, Time Factors, Case Control Studies, Hematopoietic Stem Cell Transplantation, Disease Free Survival, Cause of death, Vincristine, Cardiovascular medicine and haematology, and Paediatrics and reproductive medicine
To evaluate centralized primary care of advanced ovarian and fallopian tube cancers in a complete population cohort in relation to complete cytoreduction, time interval from surgery to chemotherapy and relative survival. A regional... more
To evaluate centralized primary care of advanced ovarian and fallopian tube cancers in a complete population cohort in relation to complete cytoreduction, time interval from surgery to chemotherapy and relative survival. A regional population-based cohort study of women diagnosed with primary ovarian and fallopian tube cancers and included in the Swedish Quality Registry (SQR) during 2008-2013 in a region where primary care of advanced stages was centralized in 2011. Surgical, oncological characteristics, outcomes, follow-ups and relative survivals were analyzed. There were 817 women diagnosed with ovarian and fallopian tube cancers during 2008-2013 and 523 were classified as FIGO stage III-IV and further analyzed. Primary debulking surgery (PDS) was performed in 81% and neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) in 11%. Complete cytoreduction at PDS was performed in 37% before compared to 49% after centralization (p&amp;amp;lt;0.03). The chemotherapy protocols were identical in the cohorts and they received and completed the planned chemotherapy equally. The time interval between PDS and chemotherapy was 36days (median) before compared to 24days after centralization (p&amp;amp;lt;0.01). The relative 3-year survival rate in women treated by PDS was 44% compared to 65% after centralization and the estimated excess mortality rate ratio (EMRR) was reduced (RR 0.58; 95% CI 0.42-0.79). Comparing the complete cohorts before and after centralization, regardless primary treatment, the relative 3-year survival rate increased from 40% to 61% with reduced EMRR (RR 0.59; 95% CI 0.45-0.76). Centralized primary care of advanced ovarian and fallopian tube cancers increases complete cytoreduction, decreases time interval from PDS to chemotherapy and improves relative survival significantly.
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Studies have causally linked external thyroid radiation exposure in childhood with thyroid cancer. In 1995, investigators conducted relative risk analyses of pooled data from seven epidemiologic studies. Doses were mostly <10 Gy,... more
Studies have causally linked external thyroid radiation exposure in childhood with thyroid cancer. In 1995, investigators conducted relative risk analyses of pooled data from seven epidemiologic studies. Doses were mostly <10 Gy, although childhood cancer therapies can result in thyroid doses >50 Gy. We pooled data from 12 studies of thyroid cancer patients who were exposed to radiation in childhood (ages <20 years), more than doubling the data, including 1,070 (927 exposed) thyroid cancers and 5.3 million (3.4 million exposed) person-years. Relative risks increased supralinearly through 2-4 Gy, leveled off between 10-30 Gy and declined thereafter, remaining significantly elevated above 50 Gy. There was a significant relative risk trend for doses <0.10 Gy (P < 0.01), with no departure from linearity (P = 0.36). We observed radiogenic effects for both papillary and nonpapillary tumors. Estimates of excess relative risk per Gy (ERR/Gy) were homogeneous by sex (P = 0.35)...
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Active surveillance (AS) has become a well-accepted and widely used treatment strategy. To assess the long-term safety of AS for men with screen-detected prostate cancer (PCa). All men with screen-detected PCa who had very low-, low-, or... more
Active surveillance (AS) has become a well-accepted and widely used treatment strategy. To assess the long-term safety of AS for men with screen-detected prostate cancer (PCa). All men with screen-detected PCa who had very low-, low-, or intermediate-risk PCa and were managed with AS (January 1, 1995 to December 31, 2014) in the Göteborg screening trial. Prostate-specific antigen tests every 3-12 mo, rebiopsies in cases of clinical progression, and every 2-3 yr in men with stable disease. Triggers for intervention were disease progression (prostate-specific antigen, grade, and/or stage) or patient initiative. Treatment-free, failure-free, PCa-specific, and overall survival. The Kaplan-Meier method and Cox proportional hazards models were used. Four-hundred and seventy-four men were managed with AS (median age at diagnosis 66.0 yr, median follow-up 8.0 yr). Two-hundred and two men discontinued AS and initiated treatment. The 10-yr and 15-yr treatment-free survival was 47% and 34%, respectively. The hazard ratio for the treatment for low- and intermediate-risk PCa, compared with very low risk, was 1.4 (95% confidence interval [CI] 1.01-1.94) and 1.6 (95% CI 1.13-2.25). Fifty-four men failed AS. The 10-yr and 15-year failure-free survival was 87% and 72%, respectively. These estimates were 94% and 88% for the very low-risk group, 85% and 77% for the low-risk group, and 73% and 40% for the intermediate-risk group. The hazard ratio for failure for low- and intermediate-risk PCa, compared with very low-risk, was 2.2 (95% CI 1.05-4.47) and 4.8 (95% CI 2.44-9.33). Six men died from PCa and none had very low-risk PCa. The 10-yr and 15-yr PCa-specific survival was 99.5% and 96%, respectively. These estimates were 100% for the very low-risk group, 100% and 94% for the low-risk group, and 98% and 90% for the intermediate-risk group. No predefined protocol was used. AS is safe for men with very low-risk PCa, but for men with low- and intermediate-risk PCa, AS carries a risk of missing the possibility of being able to cure the cancer. It is questionable whether men who are not in the lowest tumor risk group and who have a long remaining life expectancy are suitable candidates for this strategy. Long-term results from this study indicate that some men will miss their chance of cure with active surveillance and it is questionable whether active surveillance is a suitable strategy for men who are not in the lowest tumor risk group and who have a very long remaining life expectancy.
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Research Interests: Adolescent, Sweden, Humans, Female, Melanoma, and 8 moreMale, Young Adult, Registries, Aged, Middle Aged, Adult, Educational Status, and Socioeconomic Factors
In a previous publication from the Göteborg randomised screening trial from 2010, biennial prostate-specific antigen (PSA) screening for men ≤69 yr of age was shown to lower prostate cancer (PCa) mortality by 44%. The evidence of the... more
In a previous publication from the Göteborg randomised screening trial from 2010, biennial prostate-specific antigen (PSA) screening for men ≤69 yr of age was shown to lower prostate cancer (PCa) mortality by 44%. The evidence of the optimal age to stop screening, however, is limited. To examine the risk of PCa after the discontinuation of screening. In December 1994, 20 000 men in Göteborg, Sweden, between the ages of 50 and 65 yr were randomised to a screening arm (invited biennially to PSA testing) and a control arm (not invited). At the upper age limit (average: 69 yr), a total of 13 423 men (6449 and 6974 in the screening and control arms, respectively) were still alive without PCa. The incidence of PCa hereafter was established by matching with the Western Swedish Cancer Register. Participants were followed until a diagnosis of PCa, death, or final follow-up on June 30, 2012, or for a maximum of 12 yr after the last invitation. Incidence rates and disease-free survival were calculated with life table models and Kaplan-Meier estimates. A competing risk model was also applied. Postscreening, 173 cases of PCa were diagnosed in the screening arm (median follow-up: 4.8 yr) and 371 in the control arm (median follow-up: 4.9 yr). Up to 9 yr postscreening, all risk groups were more commonly diagnosed in the control arm, but after 9 yr the rates in the screening arm caught up, other than those for the low-risk group. PCa mortality also caught up after 9 yr. Nine years after the termination of PSA testing, the incidence of potentially lethal cancers equals that of nonscreened men. Considering the high PCa mortality rate in men &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;80 yr of age, a general age of 70 yr to discontinue screening might be too low. Instead, a flexible age to discontinue based on individual risk stratification should be recommended.
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... Westin, Solleftea; Lars-Olof Andersson, Ornskoldsvik; Anita Bjurman, Lycksele; Karin Forsberg, Skelleftea; Dan Fors, Pitea ... 11.↵ Avvisati G, Mandelli F. The role of interferon-α in the management of ... 12.↵ Montuoro A, De Rosa L,... more
... Westin, Solleftea; Lars-Olof Andersson, Ornskoldsvik; Anita Bjurman, Lycksele; Karin Forsberg, Skelleftea; Dan Fors, Pitea ... 11.↵ Avvisati G, Mandelli F. The role of interferon-α in the management of ... 12.↵ Montuoro A, De Rosa L, De Blasio A, Pacilli L, Petti N, De Laurenzi A. Alpha ...
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Purpose To evaluate the effect of adjuvant radiotherapy (RT) after breast conservation surgery in different breast cancer subtypes in a large, randomized clinical trial with long-term follow-up. Patients and Methods Tumor tissue was... more
Purpose To evaluate the effect of adjuvant radiotherapy (RT) after breast conservation surgery in different breast cancer subtypes in a large, randomized clinical trial with long-term follow-up. Patients and Methods Tumor tissue was collected from 1,003 patients with node-negative, stage I and II breast cancer who were randomly assigned in the Swedish Breast Cancer Group 91 Radiotherapy trial between 1991 and 1997 to breast conservation surgery with or without RT. Systemic adjuvant treatment was sparsely used (8%). Subtyping was performed with immunohistochemistry and in situ hybridization on tissue microarrays for 958 tumors. Results RT reduced the cumulative incidence of ipsilateral breast tumor recurrence (IBTR) as a first event within 10 years for luminal A–like tumors (19% v 9%; P = .001), luminal B–like tumors (24% v 8%; P < .001), and triple-negative tumors (21% v 6%; P = .08), but not for human epidermal growth factor receptor 2–positive (luminal and nonluminal) tumors (1...
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Exposure to ionizing radiation is a known risk factor for breast cancer and the fertility pattern is a recognized modifier of breast cancer risk. The aim of this study was to elucidate the interaction between these 2 factors. This study... more
Exposure to ionizing radiation is a known risk factor for breast cancer and the fertility pattern is a recognized modifier of breast cancer risk. The aim of this study was to elucidate the interaction between these 2 factors. This study is based on a Swedish cohort of 17 202 women who had been irradiated for skin haemangiomas in infancy between 1920 and 1965. The mean age at treatment was 6 months and the median breast dose was 0.05 Gy (range 0-35.8 Gy). Follow-up information on vital status, parity, age at first childbirth and breast cancer incidence was retrieved through record linkage with national population registers for the period 1958-1995. Analyses of excess relative risk (ERR) models were performed using Poisson regression methods. In this cohort, the fertility pattern differed from that in the Swedish population, with significantly fewer childbirths overall and before 25 years of age but more childbirth after that age. There were 307 breast cancers in the cohort and the st...
Research Interests: Breast Cancer, Stratification, Sweden, Postmenopausal Women, Humans, and 22 moreRecord Linkage, Female, Poisson regression, Cohort Study, Infant, Risk factors, Registries, Newborn Infant, Aged, Middle Aged, Adult, Birth Rate, Maternal Age, Interaction effect, Risk Factors, Ionizing Radiation, Parity, Age Groups, Age of Onset, Cohort Studies, Relative Risk, and Skin Neoplasms
The cohort of 17,200 female Swedish hemangioma patients, who had been exposed to ionizing radiation because of skin hemangioma, was analyzed for breast cancer incidence with descriptive excess relative risk models and mechanistic models... more
The cohort of 17,200 female Swedish hemangioma patients, who had been exposed to ionizing radiation because of skin hemangioma, was analyzed for breast cancer incidence with descriptive excess relative risk models and mechanistic models of carcinogenesis. The dosimetry system has recently been updated, leading to substantially reduced doses for the most highly exposed part of the Stockholm cohort. The follow-up includes persons until December 2009 with 877 breast cancer cases. All models agree on the risk estimates. The excess relative and excess absolute risk at the age of 50 years are 0.48Gy(-1) (95% CI 0.28; 0.69) and 10.4 [Formula: see text] (95% CI 6.1; 14.4), respectively. These risk estimates are about a factor of 2 higher than previous analyses of this cohort as a consequence of the re-evaluation of the dosimetry system. Explicit models incorporating effects of genomic instability were developed and applied to the hemangioma cohort. It was found that a radiation-induced tran...
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The aim of this study was to investigate the effect of age and number of screens on the risk of prostate cancer (PCa) diagnosis. The Göteborg randomized population-based PCa screening trial has, since 1995, invited men biennially for... more
The aim of this study was to investigate the effect of age and number of screens on the risk of prostate cancer (PCa) diagnosis. The Göteborg randomized population-based PCa screening trial has, since 1995, invited men biennially for prostate-specific antigen (PSA)-testing, until the upper age limit 70 years. Men with a PSA-level above the threshold ≥2.5 ng/ml were recommended further work-up including 10-core biopsy (sextant before 2009). The present study comprises 9,065 men born 1930-43 (1944 excluded due to different screening algorithm). Complete attendees were defined as men who accepted all screening invitations (maximum 3-9 invitations). Cumulative incidence of PCa was calculated using standard methods. Of the 3,488 (38%) complete attendees, 667 were diagnosed with PCa (follow-up 1995-30 Jun 2014). At the age 70, there was no significant difference in PCa risk between those who started screening at the age of 52 (9 screens), 55 (7 screens) or 60 (5 screens) years. However, the cumulative risk of PCa diagnosis increased dramatically with age and was 7.9% at age 60, 15% at age 65 and 21% at age 70, for men who had been screened ≥4 times. There was no clear association between risk of PCa and the number of screens. Starting screening at an early age appears to advance the time of PCa diagnosis but does not seem to increase the risk of being diagnosed with the disease. Age at termination of screening is strongly associated with the risk of being diagnosed with PCa.
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ABSTRACT Background. In patients with primary liver cancer (PLC), we recently found that the kidney appeared to be the most common site of an extrahepatic primary malignancy.Objective. To establish a possible association between PLC and... more
ABSTRACT Background. In patients with primary liver cancer (PLC), we recently found that the kidney appeared to be the most common site of an extrahepatic primary malignancy.Objective. To establish a possible association between PLC and kidney cancer (KC).Methods. The study included all cases of PLC (n=14168) and KC (n=34304) reported to the Swedish Cancer Registry between the years 1958 and 1995. Both malignancies were reported in 92 cases. A Poisson model was used to estimate the hazard function of KC and PLC after the diagnosis of PLC and KC, respectively.The probability that a new cancer will be detected after PLC and KC, respectively, was calculated from the hazard function.Results. The probability of a new cancer within one year after PLC and KC diagnosis at the age of 70, was 2.05% considering KC and 1.30% considering PLC, respectively. The corresponding probability of KC and PLC in an individual randomly selected from the population at the age of 70 is 0.056 and 0.024%, respectively.Conclusions. In a low incidence area of PLC this malignancy and KC seem to be parallel phenomenons in many patients. This finding may imply an existence of at least one common, unknown aetiologic factor for these two cancers.
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Endometrial cancer is the most abundant female gynecologic malignancy, ranking fourth in incidence among invasive tumors in women. Females of the BDII inbred rat strain are extremely prone to endometrial adenocarcinoma (EAC), and... more
Endometrial cancer is the most abundant female gynecologic malignancy, ranking fourth in incidence among invasive tumors in women. Females of the BDII inbred rat strain are extremely prone to endometrial adenocarcinoma (EAC), and approximately 90% of virgin females spontaneously develop EAC during their lifetime. Thus, these rats serve as a useful model for the genetic analysis of this malignancy. In the present work, gene expression profiling, by means of cDNA microarrays, was performed on cDNA from endometrial tumor cell lines and from cell lines derived from nonmalignant lesions/normal tissues of the endometrium. We identified several genes associated with the transforming growth factor-beta (TGF-beta) pathway to be differentially expressed between endometrial tumor cell lines and nonmalignant lesions by using clustering and statistical inference analyses. The expression levels of the genes involved in the TGF-beta pathway were independently verified using semiquantitative reverse-transcription polymerase chain reaction. Repressed TGF-beta signaling has been reported previously in EAC carcinogenesis, but this is the first report demonstrating aberrations in the expression of TGF-beta downstream target genes. We propose that the irregularities present in TGF-beta pathway among the majority of the EAC tumor cell lines may affect EAC carcinogenesis.
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The incidence of breast cancer was studied in a cohort of 17,202 women irradiated for skin hemangioma in infancy at the Radiumhemmet, Stockholm, or the Sahlgrenska University Hospital, Gothenburg. A major part of the cohort had been... more
The incidence of breast cancer was studied in a cohort of 17,202 women irradiated for skin hemangioma in infancy at the Radiumhemmet, Stockholm, or the Sahlgrenska University Hospital, Gothenburg. A major part of the cohort had been treated with radium-226 applicators, and the mean absorbed dose to the breasts was 0.29 Gy (range &lt;0.01-35.8 Gy). Two hundred forty-five breast cancers were diagnosed in the cohort during the period 1958-1993, and the standardized incidence ratio (SIR) was 1.20 (95% CI 1.06-1.36). Different dose-response models were tested, and a linear model gave the best fit. Neither age at exposure, breast dose rate, ovarian dose nor time since exposure had any statistically significant modifying effect, and breast dose was the only determinant of risk. The excess relative risk per gray (ERR/Gy) was 0.35 (95% CI 0.18-0.59), which is lower than in most other studies.
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ABSTRACT Objective: The Swedish Head and Neck Cancer Register (SweHNCR) started in 2008. The purpose was to register all new patients with head and neck cancer and collect data about tumor stage, planned and received treatment, relapse... more
ABSTRACT Objective: The Swedish Head and Neck Cancer Register (SweHNCR) started in 2008. The purpose was to register all new patients with head and neck cancer and collect data about tumor stage, planned and received treatment, relapse and survival. Data for oral cancer from the first 3 years will be presented. Method: The SweHNCR is covering more than 95% of all HN cancers in Sweden. Between 2008 and 2010, 3701 new cases were registered including 1029 of oral cancers (28%). The most common location was tongue (42%), followed by gingival (21%), buccal mucosa (19%), floor of the mouth (14%), and hard palate (3%). Less than 10% were treated with palliative intent. Results: Sixty percent of all gingival cancers were diagnosed as T4 while 70% of the tongue cancers were diagnosed as T1-T2. A total of 25% had lymphnode metastasis, range 27% (tongue) to 12% (hard palate). Surgery was the most common treatment (38%), followed by combinations of surgery and radiotherapy (36%), 19% were treated with radiotherapy alone or combined with chemotherapy, and 7% did not receive any treatment. The 2-year survival was 69% (hard palate 83%, buccal mucosa 74%, gingival 70%, tongue 69%, and floor of the mouth 63%). Data regarding treatment and stage of the disease will be further analyzed together with survival data. Conclusion: Oral cancer is the most common HN cancer location in Sweden. Almost all patients are given curative treatment (90%) consisting of surgery alone or in combination with radiotherapy (70%). The 2-year survival rate varied between 63% to 83%. Different treatment policies and survival rate was found within the country. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2012.