Publications by authors named "Sandra Eloranta"

85 Publications

Parenthood Rates and Use of Assisted Reproductive Techniques in Younger Hodgkin Lymphoma Survivors: A Danish Population-Based Study.

J Clin Oncol 2021 Jun 25:JCO2100357. Epub 2021 Jun 25.

Department of Hematology, Aalborg University Hospital, Aalborg, Denmark.

Purpose: The majority of young adults with Hodgkin lymphoma (HL) are cured, but chemotherapy-induced infertility can have profound psychosocial consequences. Providing data on parenthood rates and use of assisted reproductive techniques (ARTs) after contemporary HL treatment is important for patient counseling and survivorship care.

Materials And Methods: All Danish patients with HL diagnosed during 2000-2015 at the ages 18-40 years who achieved remission after first-line therapy were included and matched on age, sex, and parenthood status to five random persons from the general population. Parenthood rates were defined as the rate of first live birth per 1,000 person years, starting 9 months after HL diagnosis. Nationwide birth and patient registers were used to capture parenthood outcomes and ARTs use.

Results: A total of 793 HL survivors and 3,965 comparators were included (median follow-up 8.7 years). Similar parenthood rates were observed for male and female HL survivors when compared with matched comparators (56.2 57.1; = .871 for males and 63.8 61.2; = .672 for females). For male HL survivors, BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) therapy was associated with lower parenthood rates as compared to the matched comparators (28.1 60.8; = .020). Live birth after ARTs were more common for HL survivors than for comparators (males 21.6% 6.3%; < .001; females 13.6% 5.5%; = .001). There were no differences in gestational age, Apgar score, or newborn measurements between HL survivors and matched comparators.

Conclusion: The parenthood rates for HL survivors who have not experienced relapse were generally similar to the general population. However, ARTs were used more often before the first live birth in HL survivors, which is relevant information when discussing possible long-term side effects and fertility-preserving treatment options.
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http://dx.doi.org/10.1200/JCO.21.00357DOI Listing
June 2021

Real world treatment utilization patterns in patients with castration-resistant prostate cancer.

Scand J Urol 2021 Jun 7:1-8. Epub 2021 Jun 7.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Background: Studies describing treatment utilization for castration-resistant prostate cancer (CRPC) are limited. We aimed to describe the treatment utilization of a contemporary population-based CRPC cohort between 2006 and 2016.

Methods: We identified 1699 men with a PC diagnosis between 2005 and 2015, who developed CRPC between 2006 and 2015 in the Stockholm region of Sweden. Demographic information, stage and grade at PC diagnosis, stage at CRPC, prostate-specific antigen (PSA) nadir, PSA doubling time, treatment utilization rate within 1 year of CRPC diagnosis, reason for stopping therapy, treatment sequence trajectory, overall and PC specific survival was described.

Results: Treatment for men with de novo metastatic disease ( = 463) was 32%, treatment for men with progressive metastatic disease after PC diagnosis ( = 66) was 44%, treatment for men with nonmetastatic CRPC ( = 113) was 34% and treatment for those with an unknown stage at time of CRPC diagnosis ( = 857) was 12%. Docetaxel was used in 39%, abiraterone acetate plus prednisone in 15%, enzalutamide in 13%, cabazitaxel in 11% and radium-223 in 5% of treatments. Treatment increased from 22% in 2006-2009 for metastatic cancer to 50% in 2013-2015 ( < .001). Factors associated with treatment were an unknown stage at diagnosis (OR: 0.3, 95% CI: 0.2-0.4), age ≥75 years (OR: 0.2, 95% CI: 0.1 - 0.3), PSA doubling time >3 months (OR: 0.4, 95% CI: 0.3 - 0.6) and a diagnosis between 2013 and 2015 (OR: 3.4, 95% CI: 2.0 - 5.8).

Conclusions: Despite treatment availability, in this large real-world cohort we found treatment utilization to remain low.
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http://dx.doi.org/10.1080/21681805.2021.1936626DOI Listing
June 2021

Unmarried or less-educated patients with mantle cell lymphoma are less likely to undergo a transplant, leading to lower survival.

Blood Adv 2021 03;5(6):1638-1647

Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

It is unknown how many mantle cell lymphoma (MCL) patients undergo consolidation with autologous hematopoietic cell transplantation (AHCT), and the reasons governing the decision, are also unknown. The prognostic impact of omitting AHCT is also understudied. We identified all MCL patients diagnosed from 2000 to 2014, aged 18 to 65 years, in the Swedish Lymphoma Register. Odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regression models were used to compare the likelihood of AHCT within 18 months of diagnosis. All-cause mortality was compared between patients treated with/without AHCT using hazard ratios (HRs) and 95% CIs estimated from Cox regression models. Probabilities of being in each of the following states: alive without AHCT, alive with AHCT, dead before AHCT, and dead after AHCT, were estimated over time from an illness-death model. Among 369 patients, 148 (40%) were not treated with AHCT within 18 months. Compared with married patients, never married and divorced patients had lower likelihood of undergoing AHCT, as had patients with lower educational level, and comorbid patients. Receiving AHCT was associated with reduced all-cause mortality (HR = 0.58, 95% CI: 0.40-0.85). Transplantation-related mortality was low (2%). MCL patients not receiving an AHCT had an increased mortality rate, and furthermore, an undue concern about performing an AHCT in certain societal groups was seen. Improvements in supportive functions potentially increasing the likelihood of tolerating an AHCT and introduction of more tolerable treatments for these groups are needed.
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http://dx.doi.org/10.1182/bloodadvances.2020003645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993102PMC
March 2021

A multistate model incorporating estimation of excess hazards and multiple time scales.

Stat Med 2021 04 8;40(9):2139-2154. Epub 2021 Feb 8.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

As cancer patient survival improves, late effects from treatment are becoming the next clinical challenge. Chemotherapy and radiotherapy, for example, potentially increase the risk of both morbidity and mortality from second malignancies and cardiovascular disease. To provide clinically relevant population-level measures of late effects, it is of importance to (1) simultaneously estimate the risks of both morbidity and mortality, (2) partition these risks into the component expected in the absence of cancer and the component due to the cancer and its treatment, and (3) incorporate the multiple time scales of attained age, calendar time, and time since diagnosis. Multistate models provide a framework for simultaneously studying morbidity and mortality, but do not solve the problem of partitioning the risks. However, this partitioning can be achieved by applying a relative survival framework, allowing us to directly quantify the excess risk. This article proposes a combination of these two frameworks, providing one approach to address (1) to (3). Using recently developed methods in multistate modeling, we incorporate estimation of excess hazards into a multistate model. Both intermediate and absorbing state risks can be partitioned and different transitions are allowed to have different and/or multiple time scales. We illustrate our approach using data on Hodgkin lymphoma patients and excess risk of diseases of the circulatory system, and provide user-friendly Stata software with accompanying example code.
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http://dx.doi.org/10.1002/sim.8894DOI Listing
April 2021

Incidence of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) including CNS relapse in a population-based cohort of 4243 patients in Sweden.

Blood Cancer J 2021 01 7;11(1). Epub 2021 Jan 7.

Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

We performed a national population-based study of all patients diagnosed with diffuse large B-cell lymphoma (DLBCL) in Sweden in 2007-2014 to assess treatment intent and risk of relapsed/refractory disease, including central nervous system (CNS) relapse, in the presence of competing risks. Overall, 84% of patients started treatment with curative intent (anthracycline-based) (n = 3550, median age 69 years), whereas 14% did not (n = 594, median age 84 years) (for 2% the intent was uncertain). Patients treated with curative intent had a 5-year OS of 65.3% (95% CI: 63.7-66.9). The median OS among non-curatively treated patients was 2.9 months. The 5-year cumulative incidence of relapsed/refractory disease in curative patients was 23.1% (95% CI: 21.7-24.6, n = 847). The 2-year cumulative incidence of CNS relapse was 3.0% (95% CI: 2.5-3.6, n = 118) overall, and 8.0% (95% CI: 6.0-10.6, n = 48) among patients with high CNS-IPI (4-6), when considering other relapse locations and death as competing events. The incidence of relapsed/refractory DLBCL overall and in the CNS was lower than in previous reports, still one in seven patients was not considered fit enough to start standard immunochemotherapy at diagnosis. These results are important for quantification of groups of DLBCL patients with poor prognosis requiring completely different types of interventions.
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http://dx.doi.org/10.1038/s41408-020-00403-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791057PMC
January 2021

Clinical characteristics and outcomes among 2347 patients aged ≥85 years with major lymphoma subtypes: a Nordic Lymphoma Group study.

Br J Haematol 2021 02 24;192(3):551-559. Epub 2020 Nov 24.

Department of Medicine Solna, Division of Clinical Epidemiology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.

There is a lack of data regarding treatment and prognosis for the growing group of oldest old patients with lymphoma. Therefore, we studied 2347 patients aged ≥85 years from the Danish and Swedish lymphoma registers 2000-2016 (Denmark) and 2007-2013 (Sweden). Outcome was assessed using relative survival (RS). The 2-year RS overall for patients with aggressive lymphomas was 38% [95% confidence interval (CI) 35-42%], of whom 845 (66%) patients received active treatment (chemotherapy, radiotherapy, immunotherapy, other). For aggressive lymphomas, not receiving active treatment was associated with an inferior 2-year RS of 12% (95% CI 9-17%) compared to 49% (95% CI 45-53%) for patients who received active treatment (excess mortality rate ratio 2·84, 95% CI 2·3-3·5; P < 0·0001). For patients with indolent lymphoma, the 2-year RS was 77% (95% CI 72-82%). Here, 383 (46%) patients received active treatment at diagnosis, but did not have better 2-year RS (75%, 95% CI 67-81%) compared to those who did not receive active treatment (83%, 95% CI 74-89%). We conclude that outcomes for the oldest old patients with lymphoma are encouraging for several subtypes and that active treatment is associated with improved outcome amongst the oldest old patients with aggressive lymphomas, indicating that age itself should not be a contraindication to treatment.
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http://dx.doi.org/10.1111/bjh.17250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894517PMC
February 2021

Reproductive Outcomes After Breast Cancer in Women With vs Without Fertility Preservation.

JAMA Oncol 2021 Jan;7(1):86-91

Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

Importance: The practice of fertility preservation (FP) in women with breast cancer (BC) is spreading, but long-term reproductive outcomes after FP are largely unknown.

Objective: To investigate the long-term reproductive outcomes in women who did or did not undergo FP at the time of BC diagnosis.

Design, Setting, And Participants: A Swedish nationwide cohort study was conducted to investigate the long-term reproductive outcomes of women with BC receiving FP at 1 of the regional FP programs from 1994 to 2017 (n = 425). Population comparators with BC but without history of FP (n = 850) were sampled from regional BC registers, matched on age, calendar period of diagnosis, and county. Data on live births, assisted reproductive technology (ART) use, and mortality were retrieved from population-based registers. Data analysis was performed from January to September 2020.

Exposures: History of having received FP compared with no history of FP (unexposed).

Main Outcomes And Measures: The primary outcome was hazard ratios (HRs) of live births and ART treatments following BC in women with vs without FP and the cumulative incidence of these events in the presence of the competing risk of death.

Results: Women who had undergone FP (n = 425) had lower parity (302 [71.1%] were nulliparous compared with 171 [20.1%] in the unexposed group), were younger (mean [SD] age, 32.1 [4.0] vs 33.3 [3.6] years), more often had estrogen receptor-positive tumors (289 [68.0%] vs 515 [60.6%]), and were more often scheduled for chemotherapy (399 [93.9%] vs 745 [87.7%]). Of 425 women exposed to FP, 97 (22.8%) had at least 1 post-BC live birth (mean follow-up, 4.6 years), compared with 74 of 850 women (8.7%) unexposed to FP (mean follow-up, 4.8 years). Overall, live birth rates after BC were significantly higher among women with FP (adjusted hazard ratio [aHR], 2.3; 95% CI, 1.6-3.3). The 5-year and 10-year cumulative incidence of post-BC live births was 19.4% and 40.7% among FP-exposed women vs 8.6% and 15.8% among comparators, respectively. Rates of ART use were also higher in the FP group (aHR, 4.8; 95% CI, 2.2-10.7). The all-cause mortality rate was lower in women exposed to FP (aHR, 0.4; 95% CI, 0.3-0.7), with 5-year cumulative incidence of death of 5.3% (95% CI, 3.1%-9.0%) vs 11.1% (95% CI, 8.7%-14.1%) for women with vs without FP.

Conclusions And Relevance: In this cohort study of Swedish women after a BC diagnosis, successful pregnancy after BC was possible both in women with and without FP at the time of diagnosis, but a significantly higher likelihood of post-BC live births and ART treatments was observed in women who underwent FP, without any negative association with all-cause survival. This information is valuable for health care clinicians responsible for oncologic treatment and reproductive counseling of women diagnosed with breast cancer at reproductive age.
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http://dx.doi.org/10.1001/jamaoncol.2020.5957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677871PMC
January 2021

Relative and absolute cancer risks among Nordic kidney transplant recipients-a population-based study.

Transpl Int 2020 12 25;33(12):1700-1710. Epub 2020 Sep 25.

Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Kidney transplant recipients (KTRs) have an increased cancer risk compared to the general population, but absolute risks that better reflect the clinical impact of cancer are seldom estimated. All KTRs in Sweden, Norway, Denmark, and Finland, with a first transplantation between 1995 and 2011, were identified through national registries. Post-transplantation cancer occurrence was assessed through linkage with cancer registries. We estimated standardized incidence ratios (SIR), absolute excess risks (AER), and cumulative incidence of cancer in the presence of competing risks. Overall, 12 984 KTRs developed 2215 cancers. The incidence rate of cancer overall was threefold increased (SIR 3.3, 95% confidence interval [CI]: 3.2-3.4). The AER of any cancer was 1560 cases (95% CI: 1468-1656) per 100 000 person-years. The highest AERs were observed for nonmelanoma skin cancer (838, 95% CI: 778-901), non-Hodgkin lymphoma (145, 95% CI: 119-174), lung cancer (126, 95% CI: 98.2-149), and kidney cancer (122, 95% CI: 98.0-149). The five- and ten-year cumulative incidence of any cancer was 8.1% (95% CI: 7.6-8.6%) and 16.8% (95% CI: 16.0-17.6%), respectively. Excess cancer risks were observed among Nordic KTRs for a wide range of cancers. Overall, 1 in 6 patients developed cancer within ten years, supporting extensive post-transplantation cancer vigilance.
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http://dx.doi.org/10.1111/tri.13734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756726PMC
December 2020

Concordance in survival among first-degree relatives diagnosed with indolent lymphoid malignancies including chronic lymphocytic leukemia.

Eur J Haematol 2020 Dec 29;105(6):779-785. Epub 2020 Sep 29.

Department of Medicine Solna, Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden.

Objectives: To investigate concordance in survival time among first-degree relatives with lymphoid malignancies.

Methods: By linkage of national Swedish registers, we identified 66 430 patients diagnosed with a lymphoid malignancy 1958-2016 with information on first-degree relationships and follow-up until 2017. Among these, we identified pairs of first-degree relatives with any (N = 3326) or a similar (N = 690) lymphoid malignancy subtype. We defined survival in the first-degree relative as good, expected, or poor based on tertiles of deviance residuals from a multivariable Cox regression model. Next, we used Cox regression to estimate hazard ratios (HR) of death with 95% confidence intervals (CI) among patients, using the survival of their first-degree relative as exposure and adjusting for confounders.

Results: There was no concordance in survival among first-degree relatives with any lymphoid malignancy (HR  = 1.00 (reference), HR  = 1.02, 95% CI: 0.89-1.17, HR  = 1.12, 95% CI: 0.98-1.27, P  = .08). Among first-degree relatives with indolent lymphoma, including chronic lymphocytic leukemia, those with a first-degree relative to an expected or poor survival had worse outcome compared to those with a first-degree relative with good survival (HR  = 1.44, 95% CI: 0.82-2.53, HR  = 1.79, 95% CI: 1.07-3.00, P  = .03).

Conclusion: Our results support a role of inherited factors in the outcome of indolent lymphoma, including chronic lymphocytic leukemia.
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http://dx.doi.org/10.1111/ejh.13510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702025PMC
December 2020

Risk of infections in patients with myeloproliferative neoplasms-a population-based cohort study of 8363 patients.

Leukemia 2021 02 16;35(2):476-484. Epub 2020 Jun 16.

Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.

Infections are a common complication in patients with many hematologic malignancies, however, whether patients with myeloproliferative neoplasms (MPN) also are at an increased risk of infections is largely unknown. To assess the risk of serious infections, we performed a large population-based matched cohort study in Sweden including 8 363 MPN patients and 32,405 controls using high-quality registers between the years 1992-2013 with follow-up until 2015. The hazard ratio (HR) of any infection was 2.0 (95% confidence interval 1.9-2.0), of bacterial infections 1.9 (1.8-2.0), and of viral infections 2.1 (1.9-2.3). One of the largest risk increases was that of sepsis, HR 2.6 (2.4-2.9). The HR of any infection was highest in primary myelofibrosis 3.7 (3.2-4.1), and significantly elevated in all MPN subtypes; 1.7 (1.6-1.8) in polycythemia vera and 1.7 (1.5-1.8) in essential thrombocythemia. There was no significant difference in risk of infections between untreated patients and patients treated with hydroxyurea or interferon-α during the years 2006-2013. These novel findings of an overall increased risk of infections in MPN patients, irrespective of common cytoreductive treatments, suggest the increased risk of infection is inherent to the MPN.
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http://dx.doi.org/10.1038/s41375-020-0909-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738400PMC
February 2021

Efficacy and safety of controlled ovarian stimulation using GnRH antagonist protocols for emergency fertility preservation in young women with breast cancer-a prospective nationwide Swedish multicenter study.

Hum Reprod 2020 04;35(4):929-938

Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

Study Question: How efficacious and safe are the current approaches to controlled ovarian stimulation (COS) aimed at fertility preservation (FP) in women with breast cancer (BC)?

Summary Answer: In women with BC undergoing COS aiming at egg/embryo cryopreservation, letrozole-based protocols and those randomly started were equally effective compared with conventional COS, and the overall survival was similar between the women that proceeded to FP and those who did not.

What Is Known Already: Cryopreservation of oocytes and embryos is an established method for FP in women with BC. Recent improvements to COS protocols include concomitant use of letrozole, random-cycle start day of stimulation and the use of GnRHa for the egg maturation trigger. To date, limited sample size of the available studies has not allowed investigation of differences in the efficacy of the different approaches to COS for FP in this patient population.

Study Design, Size, Duration: A prospective multicenter study with national coverage including 610 women with BC counseled between 1 January 1995 and 30 June 2017 at six Swedish FP regional programs.

Participants/materials, Setting, Methods: After counseling, 401 women elected to undergo COS. Treatments differed in the use or not of concomitant letrozole, a conventional or random-cycle day COS initiation and the use of hCG versus GnRHa trigger for oocyte maturation. Numbers of cryopreserved oocytes and embryos were defined as primary outcome. Pregnancy attempts, reproductive outcomes and long-term survival, investigated by the linking of individuals of the cohort to the total population register of the Swedish Tax Agency (up to 25 November 2018), were evaluated.

Main Results And The Role Of Chance: Using letrozole or not resulted in similar numbers of oocytes and embryos cryopreserved (meanoocytes = 9.7 versus 10 and meanembryos 4.0 versus 5.3, respectively), similar to COS with random versus conventional start (meanoocytes 9.0 versus 10.6 and meanembryos 4.8 versus 4.8). In COS with letrozole, a GnRHa trigger was associated with a higher number of oocytes retrieved (P < 0.05) and embryos cryopreserved (P < 0.005), compared with conventional hCG trigger. Of 99 women who returned to fertility clinics after cancer treatment, 32 proceeded to thawing of oocytes or embryos and 10 of them had live births. The all-cause survival between the women that underwent COS and those who did not was similar and did not differ between the two groups.

Limitations, Reasons For Caution: Data on tumor characteristics and estrogen receptor (ER) status were not known for all women at the time of FP counseling and planning of COS, thus protocols with letrozole have been used for both estrogen-sensitive and non-estrogen-sensitive BC. For the same reason, subsequent adjustment for ERs in the BC or tumor characteristics as potential confounders were not performed as these parameters were not available and did not influence the provision of FP through COS.

Wider Implications Of The Findings: The results of our study support the premise that recently introduced potential improvements to COS protocols for FP in women with BC are efficacious and safe.

Study Funding/competing Interest(s): This study was supported by research grants from the Swedish Cancer Society, the Stockholm County Council, the Percy Falk Stiftelsen, Radiumhemmets Forskningsfonder, The Swedish Breast Cancer Association and Karolinska Institutet to K.A.R.W. J.B. reports grants from Amgen, AstraZeneca, Pfizer, Roche, Sanofi-Aventis and Merck, outside the submitted work, and payment from UpToDate to Asklepios Medicine HB for a chapter on BC prediction and prognostication. All the other authors have no competing interests to report.
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http://dx.doi.org/10.1093/humrep/deaa029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192532PMC
April 2020

Survival in patients diagnosed with castration-resistant prostate cancer: a population-based observational study in Sweden.

Scand J Urol 2020 Apr 8;54(2):115-121. Epub 2020 Apr 8.

Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

This study investigated prostate cancer (PC)-specific survival and overall survival (OS) in a population-based castration-resistant PC (CRPC) cohort. Data from Stockholm Prostate-Specific Antigen (PSA) and Biopsy Register patients with increasing PSA despite gonadotropin-releasing hormone treatment or surgical castration ( = 1,712) included PSA values and biopsies from 2003 to 2015 and were linked to the National Prostate Cancer Register and Prescribed Drug Register. Kaplan-Meier method estimated PC-specific survival and OS, stratified by metastasis at PC diagnosis, and Cox regression estimated hazard ratios (HRs) for Gleason score and T-stage at PC diagnosis and for age and calendar period at CRPC onset by metastasis status at diagnosis. Median OS after CRPC onset was 23.2 months (95% CI = 21.0-25.9) among patients without metastases (M0) at primary diagnosis, and 13.2 months (11.3-14.5) among patients with metastases (M1). Median PC-specific survival from CRPC onset was 30.3 (27.5-34.1) months and 13.3 (12.1-15.8) months for M0 and M1 patients, respectively. Biopsy Gleason score ≥ 8 was associated with higher all-cause mortality than ≤6 (HR = 2.07 [95% CI = 1.43-3.01]) and PC-specific mortality (2.07 [1.27-3.40]) after CRPC among patients with M0 disease. Patients developing CRPC from 2012 onward had lower all-cause mortality (HR = 0.71 [95% CI = 0.60-0.85] [M0]; 0.60 [0.47-0.77] [M1]) and PC-specific mortality (0.73 [0.57-0.94] [M0]; 0.62 [0.46-0.84] [M1]) compared with those prior to 2012. M1 disease at PC diagnosis was associated with worse survival after CRPC onset versus M0. Higher Gleason score at diagnosis was associated with higher mortality after CRPC onset in M0 patients at diagnosis.
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http://dx.doi.org/10.1080/21681805.2020.1739139DOI Listing
April 2020

Outcome and determinants of failure to complete primary R-CHOP treatment for reasons other than non-response among patients with diffuse large B-cell lymphoma.

Am J Hematol 2020 07 3;95(7):740-748. Epub 2020 Apr 3.

Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Patients with diffuse large B-cell lymphoma (DLBCL) who fail to complete planned treatment with R-CHOP due to toxicity are sparsely described. We investigated the extent of failure to complete treatment (six cycles or more, or three cycles + RT for patients with stage I disease) with R-CHOP for reasons unrelated to non-response, the determinants of such failure and the outcome among these patients. Three thousand one hundred and forty nine adult DLBCL patients who started primary treatment with R-CHOP were identified through the Swedish lymphoma register 2007-2014. Of these, 147 (5%) stopped prematurely after 1-3 cycles of R-CHOP for reasons unrelated to non-response, 168 (5%) after 4-5 cycles and 2639 patients (84%) completed planned treatment. Additionally, 195 (6%) patients did not complete treatment due to non-response or death before treatment end. In a multivariable logistic regression model, age > 75 years, poor performance status, extranodal disease and Charlson Comorbidity Index ≥1 were significantly associated with failure to complete planned R-CHOP treatment for other reasons than non-response. Non-completion of treatment strongly correlated with survival. Five-year overall survival for patients who received 1-3 cycles was 26% (95% CI: 19%-33%), 49% (95% CI: 41%-57%) for 4-5 cycles and 76% (74%-77%) for patients who completed treatment. Failure to complete planned R-CHOP treatment is an important clinical issue associated with inferior survival. Old age and poor performance status most strongly predict such failure. These results indicate a need for improved treatment tailoring for patients with certain baseline demographics to improve tolerability and chance for treatment completion.
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http://dx.doi.org/10.1002/ajh.25789DOI Listing
July 2020

Statin use is associated with improved survival in multiple myeloma: A Swedish population-based study of 4315 patients.

Am J Hematol 2020 06 20;95(6):652-661. Epub 2020 Mar 20.

Department of Medicine, Division of Hematology, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.

Statin use has been associated with reduced cancer-specific mortality among patients with several cancer types, including multiple myeloma (MM). We aimed to further elucidate the association of statin use and dose intensity with MM survival. Using Swedish population-based national health registers, we identified all incident MM diagnoses occurring January 1, 2007 to December 31, 2013 and their drug dispensations and comorbidities. We assessed statin exposure in 6-month periods pre- and post-diagnosis, treated diagnosis as baseline for calculating survival time, and calculated hazard ratios (HR) and 95% confidence intervals (CI) of exposure-related MM-specific and all-cause mortality using Cox regression. We assessed statin exposure during the entire follow-up and risk of MM-specific mortality in a nested case-control analysis. We classified dose intensity according to American College of Cardiology/American Heart Association recommendations. We ascertained 4315 MM cases during follow-up. Statin use was associated with reduced MM-specific mortality (pre-diagnosis use multivariate-adjusted HR, 95% CI: 0.83, 0.71-0.96; 6 months post-diagnosis: 0.73, 0.60-0.89; entire follow-up: 0.65, 0.52-0.80) and (more weakly) with all-cause mortality. Intensity analyses suggested a dose-response; MM-specific mortality decreased with increasing statin intensity in all time windows (eg, 6 months post-diagnosis: low [0.76 (0.56-1.03)], medium [0.73 (0.58-0.92)], high [0.33 (0.08-1.32)] intensity). However, relatively few patients received high intensity treatment, and the trend was statistically significant only for unadjusted pre-diagnosis use. In this large population-based MM cohort, statin use was associated with improved MM-specific survival in both sexes. Randomized prospective studies are warranted to evaluate statins as adjuvant treatment in MM.
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http://dx.doi.org/10.1002/ajh.25778DOI Listing
June 2020

Trends in the prevalence, incidence and survival of non-Hodgkin lymphoma subtypes during the 21st century - a Swedish lymphoma register study.

Br J Haematol 2020 06 17;189(6):1083-1092. Epub 2020 Feb 17.

Clinical Epidemiology Division, Department of Medicin Solna, Karolinska Institutet, Stockholm, Sweden.

Non-Hodgkin lymphoma (NHL) prognosis has improved in recent years, yet the number of patients living with the diagnosis, i.e. the prevalence, has seldom been reported. The prevalence provides a measure of the burden of disease, useful for healthcare planning and to optimise resource allocation. We provide a systematic presentation of temporal trends in absolute numbers of prevalent patients by NHL subtypes, linking them to trends in incidence, survival and mortality. Patients diagnosed 2000-2016 were identified in the national Swedish lymphoma register. Incidence and mortality rates, relative survival and prevalence were estimated for NHL overall and for major clinical and morphological subtypes. Poisson regression was used to test for temporal trends. Increasing incidence and improved survival have led to a 47% increase in the five-year prevalence of NHL overall in 2016 compared to 2004. An increasing prevalence was observed for all investigated subtypes during the study period, but most notably for diffuse large B cell lymphomas among aggressive subtypes (66%), and marginal zone lymphomas among indolent subtypes (135%). This dramatic increase in NHL prevalence underscores the need to develop and evaluate alternative follow-up schemes to use resources efficiently and still ensure optimal care of lymphoma survivors.
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http://dx.doi.org/10.1111/bjh.16489DOI Listing
June 2020

The prevalence of mental health problems in elite athletes.

J Sci Med Sport 2020 Apr 2;23(4):329-335. Epub 2019 Nov 2.

Department of Clinical Neuroscience, Karolinska Institutet.

Objectives: The first aim was to examine mental health problems (MHP) in elite athletes addressing prevalence, sex-differences, onset, recurrent episodes, help-seeking, symptoms of specific disorders and previous psychiatric diagnoses. The second aim was to investigate if sport-specific instruments could indicate clinical levels of psychiatric symptoms.

Design: Cross-sectional survey.

Methods: Elite athletes representing different Swedish national teams and applying for a university scholarship (n=333) answered a web-based survey. Females represented 58.9%. Mean age was 24.6(±3.1) years and 77.2% were individual- and 22.8% team-sport athletes.

Results: Lifetime prevalence of MHP was 51.7% (females 58.2%, males 42.3%). Point prevalence was 11.7% (females 13.8%, males 8.8%). Onset of first MHP episode peaked at age 19 with 50% of onsets between ages 17-21. Recurrent episodes were common, and females sought help more than males (females 37.8%, males 16.8%). Overall 19.5% reached the clinical cut-offs for symptoms of anxiety and/or depression (females 26.0%, males 10.2%). Previous psychiatric diagnoses existed among 8.1% (females 10.7%, males 4.4%). A depressive disorder, an eating disorder or a trauma and stress related disorder (self-reported as burnout) were most common. Finally, most sport-specific instruments (80%) demonstrated a fair diagnostic accuracy compared to clinically validated instruments.

Conclusions: Lifetime prevalence of MHP was reported by more than half of the athletes. Symptoms manifested in young age and recurrent episodes were common. Sport-specific instruments indicating when symptoms reach clinical levels are potentially useful for data summary purposes on a group level, but without sufficiently high sensitivity and specificity to be recommend for applied work with athletes.
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http://dx.doi.org/10.1016/j.jsams.2019.10.022DOI Listing
April 2020

Comorbidities and sex differences in causes of death among mantle cell lymphoma patients - A nationwide population-based cohort study.

Br J Haematol 2020 04 13;189(1):106-116. Epub 2019 Nov 13.

Department of Medicine, Division of Clinical Epidemiology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.

The prognosis for mantle cell lymphoma (MCL) remains poor. Our aim was to assess the impact of comorbidities on survival and causes of death. For 1,385 MCL patients (1,009 males, 376 females) diagnosed in 2000-2014 (median age 71 years, range 22-96) comorbidities ≤ 10 years of diagnosis were classified according to the Charlson comorbidity index (CCI; 0, 1, 2+). Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated to compare lymphoma-specific and all-cause mortality rates. Model-based predictions were used to obtain probabilities of death. Overall, 44% had any comorbidity (CCI 1+) and 28% severe comorbidity (CCI 2+). Over a median follow-up of 3·7 years (range 0-16), 633 (46%) died, the majority (76%) from lymphoma. Severe comorbidity was independently associated with higher all-cause [hazard ratio (HR) = 1·52; 95% CI: 1·24-1·85) and lymphoma-specific mortality (HR = 1·31; 95% CI: 1·04-1·65). Particularly among patients with connective tissue, renal and psychiatric diseases, and dementia. Among females with any comorbidity, non-lymphoma deaths represented a larger proportion of all deaths, compared to males with any comorbidity. In general, more efficient lymphoma treatments need to be considered also for patients with severe comorbidity. However, among females with any comorbidity, the likelihood of non-lymphoma death was still considerable, perhaps favouring a more liberal use of a "wait and watch" approach.
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http://dx.doi.org/10.1111/bjh.16317DOI Listing
April 2020

Distribution of hospital care among pediatric and young adult Hodgkin lymphoma survivors-A population-based cohort study from Sweden and Denmark.

Cancer Med 2019 08 2;8(10):4918-4927. Epub 2019 Jul 2.

Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.

The burden of late effects among Hodgkin lymphoma (HL) survivors treated according to contemporary protocols remains poorly characterized. We used nation-wide registers to assess number of inpatient bed-days and specialist outpatient visits among 1048 HL-patients (<25 years, diagnosed 1990-2010) and 5175 country-, sex-, and age-matched comparators. We followed them for up to 24 years, with time-dependent assessment of relapse status. International Classification of Diseases (ICD-10) chapter-specific hazard ratios (HRs) were assessed in Cox regression analyses, and nonparametric statistics described patterns of health-care-use. Relative to comparators, relapse-free survivors were at increased risk of infections, diseases of the blood, endocrine, circulatory and respiratory systems, and unspecific symptoms, HRs ranging from 1.86 to 3.05. Relative to comparators, relapsed survivors had at statistically significantly increased risk of diseases reflecting practically all investigated disease-chapters, HRs ranging from 1.60 to 18.7. Among relapse-free survivors, 10% of the patients accounted for 80% of all hospital bed days, and 55% were never hospitalized during follow-up. Among relapsed-survivors, 10% of the patients accounted for 50% of the bed days, and only 24% were never hospitalized during follow-up. In contrast, 10% of the comparators accounted for 90% of hospital bed days and 75% were never hospitalized. These findings challenge the impression of a uniformly distributed long-term morbidity among all HL survivors and emphasize the need for early identification and attention to patients particularly susceptible to late effects, such as relapsed survivors.
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http://dx.doi.org/10.1002/cam4.2363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712477PMC
August 2019

Author's reply to: A note on competing risks in analyses of cancer-specific mortality.

Int J Cancer 2019 09 28;145(6):1706-1707. Epub 2019 Jun 28.

Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

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http://dx.doi.org/10.1002/ijc.32517DOI Listing
September 2019

Validation of data quality in the Swedish National Register for Breast Cancer.

BMC Public Health 2019 May 2;19(1):495. Epub 2019 May 2.

Department of Molecular Medicine and Surgery Karolinska Institutet, Stockholm, Sweden.

Background: The National Breast Cancer Register (NBCR) of Sweden was launched in 2008 and is used for quality assurance, benchmarking, and research. Its three reporting forms encompass Notification, Adjuvant therapy and Follow-up. Target levels are set by national and international guidelines. This national validation assessed data quality of the register.

Methods: Data recorded through the Notification form were evaluated for completeness, timeliness, comparability and validity. Completeness was assessed by cross-linkage to the Swedish Cancer Register (SCR). Comparability was analyzed by comparing registration routines in NBCR with national and international guidelines. Timeliness was defined as the difference between the earliest date of diagnosis and the reporting date to NBCR. Validity was assessed by re-abstraction of medical chart data for 800 randomly selected patients diagnosed in 2013.

Results: The completeness of the NBCR was high with a coverage across regions and years (2010-2014) of 99.9%. Of all incident cases reported to the NBCR in 2013 (N = 8654), 98.5% were included within 12 months and differences between health regions were essentially negligible. Coding procedures followed guidelines and were uniformly adhered to. The proportion of missing values was < 5% for most variables and reported information generally had high exact agreement (> 90%).

Conclusions: Completeness of data, comparability and agreement in the NBCR was high. For clinical quality purposes and benchmarking, improved timeliness is warranted. Assessment of validity has resulted in a thorough review of all variables included in the Notification form with clarifications and revision of selected variables.
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http://dx.doi.org/10.1186/s12889-019-6846-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6498669PMC
May 2019

Survival among solid organ transplant recipients diagnosed with cancer compared to nontransplanted cancer patients-A nationwide study.

Int J Cancer 2020 02 11;146(3):682-691. Epub 2019 Apr 11.

Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Solid organ transplant recipients (OTRs) have an increased cancer risk but their survival once diagnosed with cancer has seldom been assessed. We therefore investigated cancer-specific survival among OTRs with a wide range of cancer forms nationally in Sweden. The study included 2,143 OTRs with cancer, and 946,089 nontransplanted cancer patients diagnosed 1992-2013. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression models adjusted for age, sex and calendar year. Median follow-up was 3.1 (range 0-22) years. Overall, OTRs diagnosed with any cancer had a 35% higher rate of cancer death compared to nontransplanted cancer patients (HR: 1.35, 95% CI: 1.24-1.47). Specifically, higher rates of cancer-specific death were observed among OTRs diagnosed with Hodgkin lymphoma (HR: 15.0, 95% CI: 5.56-40.6), high-grade non-Hodgkin lymphoma (HR: 2.68, 95% CI: 1.90-3.77), malignant melanoma (HR: 2.80, 95% CI: 1.74-4.52) and urothelial (HR: 2.56, 95% CI: 1.65-3.97), breast (HR: 2.12, 95% CI: 1.38-3.25), head/neck (HR: 1.55, 95% CI: 1.02-2.36) and colorectal (HR: 1.42, 95% CI: 1.07-1.88) cancer. The worse outcomes were not explained by differences in distribution of cancer stage or histologic subtypes. For other common cancer forms such as prostate, lung and kidney cancer, the prognosis was similar to that in nontransplanted cancer patients. In conclusion, several but not all types of posttransplantation cancer diagnoses are associated with worse outcomes than in the general population. Reasons for this should be further explored to optimize posttransplantation cancer management.
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http://dx.doi.org/10.1002/ijc.32299DOI Listing
February 2020

Relapse Risk and Loss of Lifetime After Modern Combined Modality Treatment of Young Patients With Hodgkin Lymphoma: A Nordic Lymphoma Epidemiology Group Study.

J Clin Oncol 2019 03 6;37(9):703-713. Epub 2019 Feb 6.

3 Karolinska Institutet, Solna, Sweden.

Purpose: Estimates of short- and long-term survival for young patients with classic Hodgkin lymphoma (cHL) are of considerable interest. We investigated cHL prognosis in the era of contemporary treatment at different milestones during the follow-up.

Patients And Methods: On the basis of a Nordic cohort of 2,582 patients diagnosed at ages 18 to 49 years between 2000 and 2013, 5-year relapse risks and 5-year restricted losses in expectation of lifetime were estimated for all patients and for patients who achieved event-free survival (EFS) for 12 (EFS12), 24 (EFS24), 36 (EFS36) or 60 (EFS60) months. The median follow-up time was 9 years (range, 2.9 to 16.8 years).

Results: The 5-year overall survival was 95% (95% CI, 94% to 96%). The 5-year risk of relapse was 13.4% (95% CI, 12.1% to 14.8%) overall but decreased to 4.2% (95% CI, 3.8% to 4.6%) given that patients reached EFS24. Relapse risk for patients treated with six to eight courses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) was comparable to that of patients treated with six to eight courses of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) despite more adverse risk criteria among patients treated with BEACOPP. Both from diagnosis and if EFS24 was reached, the losses in expectation of lifetime during the following 5 years were small (from diagnosis, 45 days [95% CI, 35 to 54 days] and for patients who reached EFS24, 13 days [95% CI, 7 to 20 days]). In stage-stratified analyses of 5-year restricted loss in expectation of lifetime, patients with stages I to IIA disease had no noteworthy excess risk of death after they reached EFS24, whereas risk remained measurable for patients with stages IIB to IV cHL.

Conclusion: Real-world data on young patients with cHL from the Nordic countries show excellent outcomes. The outlook is particularly favorable for patients who reach EFS24, which supports limited relapse-oriented clinical follow-up.
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http://dx.doi.org/10.1200/JCO.18.01652DOI Listing
March 2019

Temporal trends in treatment-related incidence of diseases of the circulatory system among Hodgkin lymphoma patients.

Int J Cancer 2019 09 5;145(5):1200-1208. Epub 2019 Feb 5.

Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

While Hodgkin lymphoma (HL) survival has improved, treatment-related complications remain a concern. As a measure of treatment-related diseases of the circulatory system (DCS) we report excess incidence of DCS and absolute risks among HL patients diagnosed in the modern treatment era. From the Swedish Cancer Register, we identified all HL patients diagnosed 1985 through 2013, at ages 18-80 years. Excess incidence rate ratios (EIRRs) with 95% confidence intervals (CIs) comparing excess DCS incidence between calendar periods were estimated overall, and at 5 and 10 years after diagnosis using flexible parametric models. Model-based predictions were used to obtain probabilities of being diagnosed with DCS, in the presence of competing risks. During follow-up, 726 (16%) of the 4,479 HL patients experienced DCS. Overall, the excess DCS incidence was lower during all calendar periods compared to the first (2009-2013 vs. 1985-1988: EIRR = 0.63, 95% CI: 0.42-0.95). The 5- and 10-year excess incidence of DCS decreased between 1985 and 1994 for 25-year-olds (5-year-EIRR  = 0.32, 95% CI: 0.12-0.92) and 60-year-olds (5-year-EIRR  = 0.45, 95% CI: 0.24-0.88), but remained stable thereafter. No improvements were observed among 75-year-olds. The probability of excess DCS remained the same throughout the study period. In 2009, the percentage of patients aged 25, 60 and 75 experiencing excess DCS within 5 years was 3.4, 15.0 and 17.0% (males) and 2.3, 10.8 and 12.6% (females). Treatment-related incidence of DCS has declined since the mid-1980s, but more recent improvements are absent and an excess risk remains. Continued efforts towards less toxic treatments are warranted, alongside primary prevention strategies.
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http://dx.doi.org/10.1002/ijc.32142DOI Listing
September 2019

Optimizing Outcome Prediction in Diffuse Large B-Cell Lymphoma by Use of Machine Learning and Nationwide Lymphoma Registries: A Nordic Lymphoma Group Study.

JCO Clin Cancer Inform 2018 12;2:1-13

Jorne L. Biccler, Lasse Hjort Jakobsen, Martin Bøgsted, and Tarec C. El-Galaly, Aalborg University Hospital and Aalborg University, Aalborg; Peter de Nully Brown, Copenhagen University Hospital, Copenhagen; Henrik Frederiksen, Odense University Hospital, Odense; Judit Jørgensen, Aarhus University Hospital, Aarhus; Denmark; Sandra Eloranta and Karin E. Smedby, Karolinska Institutet, Stockholm; Mats Jerkeman, Lund University, Lund; and Karin E. Smedby, Karolinska University Hospital, Solna, Sweden.

Purpose: Prognostic models for diffuse large B-cell lymphoma (DLBCL), such as the International Prognostic Index (IPI) are widely used in clinical practice. The models are typically developed with simplicity in mind and thus do not exploit the full potential of detailed clinical data. This study investigated whether nationwide lymphoma registries containing clinical data and machine learning techniques could prove to be useful for building modern prognostic tools.

Patients And Methods: This study was based on nationwide lymphoma registries from Denmark and Sweden, which include large amounts of clinicopathologic data. Using the Danish DLBCL cohort, a stacking approach was used to build a new prognostic model that leverages the strengths of different survival models. To compare the performance of the stacking approach with established prognostic models, cross-validation was used to estimate the concordance index (C-index), time-varying area under the curve, and integrated Brier score. Finally, the generalizability was tested by applying the new model to the Swedish cohort.

Results: In total, 2,759 and 2,414 patients were included from the Danish and Swedish cohorts, respectively. In the Danish cohort, the stacking approach led to the lowest integrated Brier score, indicating that the survival curves obtained from the stacking model fitted the observed survival the best. The C-index and time-varying area under the curve indicated that the stacked model (C-index: Denmark [DK], 0.756; Sweden [SE], 0.744) had good discriminative capabilities compared with the other considered prognostic models (IPI: DK, 0.662; SE, 0.661; and National Comprehensive Cancer Network-IPI: DK, 0.681; SE, 0.681). Furthermore, these results were reproducible in the independent Swedish cohort.

Conclusion: A new prognostic model based on machine learning techniques was developed and was shown to significantly outperform established prognostic indices for DLBCL. The model is available at https://lymphomapredictor.org .
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http://dx.doi.org/10.1200/CCI.18.00025DOI Listing
December 2018

No association between low-dose aspirin use and breast cancer outcomes overall: a Swedish population-based study.

Breast Cancer Res 2018 11 20;20(1):142. Epub 2018 Nov 20.

Department of Medicine Solna, Division of Clinical Epidemiology, Karolinska Institutet and Karolinska University Hospital, SE-171 76, Stockholm, Sweden.

Background: Results from previous studies indicate that use of low-dose aspirin may improve breast cancer prognosis. We evaluated aspirin use and breast cancer outcomes in relation to clinical characteristics as well as dose and duration of aspirin use.

Methods: We used information from the Regional Breast Cancer Quality-of-Care Registries in three Swedish regions to identify 21,414 women diagnosed with a first stage I-III breast cancer between 1 April 2006 and 31 December 2012. The cohort was further linked to nationwide registers to retrieve information about dispensing low-dose aspirin before and after breast cancer diagnosis, comorbidity and causes of death. In a separate analysis, we investigated time to breast cancer death among 621 women with stage IV disease at diagnosis. Associations were evaluated using a multivariable Cox proportional hazards model.

Results: Among women with stage I-III breast cancer, 2660 (12.4%) used low-dose aspirin shortly before breast cancer diagnosis and 4091 (19.1%) were users during follow-up. Women were followed for a median of 3.8 years after diagnosis. There was no association between aspirin use and breast cancer-specific death in multivariable analyses (use before diagnosis: hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.77-1.12; use after diagnosis: HR 1.00, 95% CI 0.74-1.37). Similarly, aspirin use was not associated with risk of first recurrence/metastases in a subgroup of stage I-III breast cancer patients (HR 0.97, 95% CI 0.86-1.10). However, in analyses stratified by stage, an inverse association between low-dose aspirin use after diagnosis and breast cancer death was found for women with stage I tumors (HR 0.53, 95% CI 0.29-0.96). Among women with stage IV disease at diagnosis, aspirin use was not associated with time to breast cancer death (HR 0.91, 95% CI 0.67-1.23).

Conclusion: In this large population-based cohort study there was no evidence that low-dose aspirin use before or after breast cancer diagnosis is associated with a reduced risk of adverse outcomes overall in breast cancer. However, a potential benefit was noted among women with stage I tumors, warranting further investigation.
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http://dx.doi.org/10.1186/s13058-018-1065-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247765PMC
November 2018

Post-mastectomy radiation therapy with or without implant-based reconstruction is safe in terms of clinical target volume coverage and survival - A matched cohort study.

Radiother Oncol 2019 02 25;131:229-236. Epub 2018 Jul 25.

Department of Oncology-Pathology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden. Electronic address:

Background And Purpose: Patients with breast cancer receiving mastectomy in our institution are offered immediate breast reconstruction (IBR). IBR may have an impact on the optimisation of radiation therapy (RT). Therefore, we aimed to evaluate the clinical target volume (CTV) dose coverage when disregarding the dose received by the breast implant in women treated for breast cancer. Furthermore, to investigate the safety of immediate breast reconstruction (IBR) with an implant (IBR+) in terms of recurrence and survival compared to patients without an implant (IBR-).

Patients And Methods: This matched-cohort included 128 patients with IBR+ and 252 IBR- patients (controls). The potential confounding effects of tumour stage and treatment were controlled for. For IBR+ patients, the implant volume was excluded from the CTV in the RT planning images, and the RT target coverage (V CTV covered by ≥the 95% isodose) was compared between the IBR+ and IBR- groups.

Results: A limited under dosage was observed in patients without lymph-node irradiation; the V mean values for the CTV subtracting the implant were 84% and 92%, for IBR+ and IBR- groups, respectively. Median follow-up duration was 5.8 years (0.1-7.5 years). In comparing IBR+ and IBR- groups, no statistically significant differences were found in the incidence of recurrence rate ratios or recurrence free survival (log-rank p = 0.142), overall survival (log-rank p = 0.096), or breast cancer specific survival (log-rank p = 0.147).

Conclusions: Post-mastectomy radiation therapy and implant-based reconstruction lead to minor under dosage of the target, due to the projection of the subcutaneous tissue in the presence of the implant. However, recurrence and survival rates were equally distributed among IBR+ and IBR- patients indicating that the overall treatment protocol used in our institution is safe.
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http://dx.doi.org/10.1016/j.radonc.2018.07.005DOI Listing
February 2019

Contemporarily Treated Patients With Hodgkin Lymphoma Have Childbearing Potential in Line With Matched Comparators.

J Clin Oncol 2018 09 25;36(26):2718-2725. Epub 2018 Jul 25.

Caroline E. Weibull, Anna L.V. Johansson, Sandra Eloranta, Paul C. Lambert, Paul W. Dickman, and Ingrid Glimelius, Karolinska Institutet; Karin E. Smedby and Magnus Björkholm, Karolinska Institutet and Karolinska University Hospital, Stockholm; Ingrid Glimelius, Uppsala University and Uppsala Akademiska Hospital, Uppsala, Sweden; Anna L.V. Johansson, Cancer Registry of Norway, Oslo, Norway; and Paul C. Lambert, University of Leicester, Leicester, United Kingdom.

Purpose With excellent cure rates for young patients with Hodgkin lymphoma (HL), there is an increasing number of female survivors of HL interested in becoming pregnant. Here, we report childbearing among contemporarily treated HL survivors in comparison with the general population. Material and Methods Using Swedish registers, 449 women (ages 18 to 40 years) diagnosed with HL between 1992 and 2009 and in remission 9 months after diagnosis were identified. Patients were age- and calendar-year-matched to 2,210 population comparators. Rates of first postdiagnosis childbirth were calculated. Hazard ratios (HRs) with 95% CIs were estimated for different follow-up periods using Cox regression. Cumulative probabilities of first childbirth were calculated in the presence of the competing risk of death or relapse. Results Twenty-two percent of relapse-free patients with HL had a child during follow-up, and first childbirth rates increased over time, from 40.2 per 1,000 person-years (1992 to 1997) to 69.7 per 1,000 person-years (2004 to 2009). For comparators, childbirth rates remained stable (70.1 per 1,000 person-years). Patients diagnosed between 2004 and 2009 had a cumulative probability of childbirth similar to comparators. Three years or more after diagnosis, no differences in childbirth rates were observed between patients and comparators, regardless of stage or treatment. Patients who received six to eight courses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone had a lower childbirth rate than comparators during the first 3 years (HR, 0.23; 95% CI, 0.06 to 0.94), as did patients who received six to eight courses of chemotherapy and radiotherapy (HR, 0.21; 95% CI, 0.07 to 0.65). Conclusion Childbearing potential among female survivors of HL has improved over time, and childbirth rates 3 years after diagnosis in contemporarily treated patients are, in the absence of relapse, similar to those in the general population, regardless of stage and treatment.
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http://dx.doi.org/10.1200/JCO.2018.78.3514DOI Listing
September 2018

Real-world evidence in safety assessment of new treatments.

Lancet Haematol 2018 Nov 12;5(11):e510-e511. Epub 2018 Jun 12.

Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska University Hospital, Stockholm 171 76, Sweden.

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http://dx.doi.org/10.1016/S2352-3026(18)30073-5DOI Listing
November 2018

Long-term survival and loss in expectancy of life in a population-based cohort of 7114 patients with diffuse large B-cell lymphoma.

Am J Hematol 2018 May 17. Epub 2018 May 17.

Division of Clinical Epidemiology, Department of Medicin Solna, Karolinska Institutet, Stockholm, Sweden.

Survival has improved among patients with diffuse large B-cell lymphoma (DLBCL) with the addition of anti-CD20 antibody therapy. We aimed to quantify trends and remaining loss in expectation of life (LEL) due to DLBCL at a national population-based level. Patients diagnosed with DLBCL 2000-2013 (N = 7114) were identified through the Swedish Lymphoma Registry and classified according to the age-adjusted International Prognostic Index (aaIPI). The novel measure LEL is the difference between remaining life years among patients and the general population and was predicted using flexible parametric models from diagnosis and among 2-year survivors, by age and sex. Median age at DLBCL-diagnosis was 70 (18-105) years and 54.8% presented with stage III-IV disease. On average, LEL due to DLBCL decreased from 8.0 (95% CI: 7.7-8.3) to 4.6 (95% CI: 4.5-4.6) years over the study period. By risk group, LEL was most reduced among patients with aaIPI ≥2 aged 50-60 years. However, these patients were still estimated to lose >8 years in 2013 (eg, LEL 8.6 years (95% CI: 5.0-12.3)). Among 2-year survivors, LEL was reduced from 6.1 years (95% CI: 5.6-6.5) (aaIPI ≥ 2) and 3.8 years (95% CI: 3.6-4.1) (aaIPI < 2) to 1.1 (95% CI: 1.1-1.2) and 1.0 year (95% CI: 0.8-1.1), respectively. The reduction was observed across all ages. Results for females were similar. By using LEL we illustrate the improvement of DLBCL survival over time. Despite adequate immunochemotherapy, substantial LEL among patients with IPI ≥ 2 points to remaining unmet medical needs. We speculate that observed reduced losses among 2-year survivors indicate a reduction of late relapses.
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http://dx.doi.org/10.1002/ajh.25147DOI Listing
May 2018

Greater attention should be paid to developing therapies for elderly patients with Hodgkin lymphoma-A population-based study from Sweden.

Eur J Haematol 2018 Jul 23;101(1):106-114. Epub 2018 May 23.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Objective: Forty percent of Hodgkin lymphoma (HL) patients are older than 50 years at diagnosis, a fact which is not commonly recognized. Older patients do significantly worse than younger patients and are rarely included in clinical trials.

Methods: Using data from Swedish Cancer and Lymphoma Registries, we estimated relative survival ratios (RSRs) for 7997 HL patients (diagnosed 1973-2013; 45% ≥50 years).

Results: The 1-year RSRs (95% confidence interval; CI) for males aged 45-59, 60-69, 70-80, and 81 years and over, diagnosed in 2013, were 0.95 (0.91-0.97), 0.88 (0.81-0.92), 0.74 (0.63-0.81), and 0.52 (0.35-0.67), respectively. The corresponding 1-year RSRs for females were 0.97 (0.94-0.98), 0.91 (0.85-0.95), 0.82 (0.73-0.88), and 0.66 (0.50-0.77). No improvements in 1-year of 5-year relative survival from 2000 to 2013 were observed for patients aged 45-59 or 60-69 but there were modest improvements for patients aged 70 years and older. Importantly, we saw no changes in the distribution of disease or patient characteristics between 2000 and 2013.

Conclusions: Elderly patients constitute a large group with clearly unmet medical needs. Our findings motivate a more active approach to including elderly patients in clinical trials. Our study provides a baseline for outcome comparison after the broader introduction of targeted drugs.
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http://dx.doi.org/10.1111/ejh.13090DOI Listing
July 2018
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