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Holmberg, Lars
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Publications (10 of 233) Show all publications
Beckmann, K., Garmo, H., Adolfsson, J., Bosco, C., Johansson, E., Robinson, D., . . . Van Hemelrijck, M. (2019). Androgen Deprivation Therapies and Changes in Comorbidity: A Comparison of Gonadotropin-releasing Hormone Agonists and Antiandrogen Monotherapy as Primary Therapy in Men with High-risk Prostate Cancer. European Urology, 75(4), 676-683
Open this publication in new window or tab >>Androgen Deprivation Therapies and Changes in Comorbidity: A Comparison of Gonadotropin-releasing Hormone Agonists and Antiandrogen Monotherapy as Primary Therapy in Men with High-risk Prostate Cancer
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2019 (English)In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 75, no 4, p. 676-683Article in journal (Refereed) Published
Abstract [en]

Background: Some studies suggest that gonadotropin-releasing hormone (GnRH) agonists are associated with higher risk of adverse events than antiandrogens (AAs) monotherapy. However, it has been unclear whether this is due to indication bias.

Objective: To investigate rates of change in comorbidity for men on GnRH agonists versus AA monotherapy in a population-based register study.

Design, setting, and participants: Men with advanced nonmetastatic prostate cancer (PCa) who received primary AA (n = 2078) or GnRH agonists (n = 4878) and age- and area-matched PCa-free men were selected from Prostate Cancer Database Sweden 3.0. Increases in comorbidity were measured using the Charlson Comorbidity Index (CCI), from 5 yr before through to 5 yr after starting androgen deprivation therapy (ADT).

Outcome measures and statistical methods: Multivariable linear regression was used to determine differences in excess rate of CCI change before and after ADT initiation. Risk of any incremental change in CCI following ADT was assessed using multivariable Cox regression analyses.

Results and limitations: Men on GnRH agonists experienced a greater difference in excess rate of CCI change after starting ADT than men on AA monotherapy (5.6% per yr, p < 0.001). Risk of any new CCI change after ADT was greater for GnRH agonists than for AA (hazard ratio, 1.32; 95% confidence interval, 1.20-144).

Conclusions: Impact on comorbidity was lower for men on AA monotherapy than for men on GnRH agonists. Our results should be confirmed through randomised trials of effectiveness and adverse effects, comparing AA monotherapy and GnRH agonists in men with advanced nonmetastatic PCa who are unsuitable for curative treatment.

Patient summary: Hormone therapies for advanced prostate cancer can increase the risk of other diseases (eg, heart disease, diabetes). This study compared two common forms of hormone therapy and found that the risk of another serious disease was higher for those on gonadotropin-releasing hormone agonists than for those on antiandrogen monotherapy.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2019
Keywords
Androgen deprivation therapy, Antiandrogen monotherapy, Comorbidity, Gonadotropin-releasing hormone agonists, Prostate cancer
National Category
Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-380435 (URN)10.1016/j.eururo.2018.11.022 (DOI)000461049200041 ()30497883 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2019-03-28 Created: 2019-03-28 Last updated: 2019-04-09Bibliographically approved
Essen, A., Santaolalla, A., Garmo, H., Hammar, N., Walldius, G., Jungner, I., . . . Van Hemelrijck, M. (2019). Baseline serum folate, vitamin B12 and the risk of prostate and breast cancer using data from the Swedish AMORIS cohort. Cancer Causes and Control, 30(6), 603-615
Open this publication in new window or tab >>Baseline serum folate, vitamin B12 and the risk of prostate and breast cancer using data from the Swedish AMORIS cohort
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2019 (English)In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 30, no 6, p. 603-615Article in journal (Refereed) Published
Abstract [en]

Purpose: The roles of folate and vitamin B12 in prostate cancer (PCa) or breast cancer (BC) development are unclear. We investigated their roles using the prospective Swedish Apolipoprotein MOrtality RISk (AMORIS) study.

Methods: 8,783 men and 19,775 women with vitamin B12 and folate serum measurements were included. Their associations with PCa and BC risk categories were evaluated using Cox proportional hazards regression.

Results: During mean follow-up of 13years, 703 men developed PCa. There was an inverse association between folate>32nmol/L and high-risk PCa [hazard ratio (HR) 0.12, 95% confidence interval (CI) 0.02-0.90], and a positive association between folate<5nmol/L and metastatic PCa (HR 5.25, 95% CI 1.29-21.41), compared with folate 5-32nmol/L. No associations with vitamin B12 were found. 795 women developed BC during mean follow-up of 14years. When restricting to the fasting population, there was a positive association between folate>32nmol/L and BC (HR 1.47, 95% CI 1.06-2.04).

Conclusion: High folate levels may protect against PCa and low folate levels may increase risk of metastatic PCa. High fasting folate levels may be associated with an increased BC risk. Vitamin B12 was not found to be linked with risk of PCa or BC. Longitudinal studies with serum and dietary information could help define new prevention targets and add information on the role of folate fortification.

Place, publisher, year, edition, pages
SPRINGER, 2019
Keywords
Prostate cancer (PCa), Breast cancer (BC), Vitamin B12, Folate, Severity
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-384996 (URN)10.1007/s10552-019-01170-6 (DOI)000467796500005 ()31020446 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2019-06-11 Created: 2019-06-11 Last updated: 2019-06-11Bibliographically approved
Plym, A., Johansson, A. L. ., Bower, H., Voss, M., Holmberg, L., Fredriksson, I. & Lambe, M. (2019). Causes of sick leave, disability pension, and death following a breast cancer diagnosis in women of working age. Breast, 45, 48-55
Open this publication in new window or tab >>Causes of sick leave, disability pension, and death following a breast cancer diagnosis in women of working age
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2019 (English)In: Breast, ISSN 0960-9776, E-ISSN 1532-3080, Vol. 45, p. 48-55Article in journal (Refereed) Published
Abstract [en]

Objectives: Women diagnosed with breast cancer during working age are at increased risk of permanent absence from work, but the underlying medical causes have rarely been studied. We examined the risk of cause-specific sick leave, disability pension, and the competing event death after a breast cancer diagnosis in a population-based cohort study.

Materials and methods: From the Breast Cancer Data Base Sweden, we identified 16,603 women diagnosed with stage I-III breast cancer between 2000 and 2012, and 63,773 control women. Using multi-state modelling, we calculated probabilities and durations of sick leave, disability pension, and death by registered cause, together with cause-specific hazard ratios.

Results: Five years after diagnosis, causes other than cancer accounted for around half of all sick leave (3.5% out of 6.8% of women) and disability pension (1.4% out of 2.6%) in women with breast cancer. Compared with control women, women with breast cancer were at increased risk of sick leave and disability pension due to mental disorders (HR 1.24, 95% CI 1.15-1.33 and HR 1.54, 95% CI 1.29-1.85, respectively) and disability pension due to inflammatory diseases (HR 1.46, 95% CI 1.05-2.03). The risk of sick leave and disability pension due to cardiovascular disease was also elevated, although only statistically significant for disability pension in women diagnosed after 2005 (HR 2.24, 95% CI 1.22-4.13).

Conclusion: Follow-up, support, and rehabilitation programs for women diagnosed with breast cancer must address a wide range of psychological and physical conditions to limit the consequences on working life.

Place, publisher, year, edition, pages
CHURCHILL LIVINGSTONE, 2019
Keywords
Breast cancer, Cause of death, Disability pension, Employment, Mental disorders, Sick leave
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-383143 (URN)10.1016/j.breast.2019.02.012 (DOI)000465411900008 ()30852409 (PubMedID)
Funder
Swedish Cancer Society, 14-0324The Breast Cancer Foundation
Available from: 2019-05-13 Created: 2019-05-13 Last updated: 2019-05-13Bibliographically approved
Beckmann, K., Russell, B., Josephs, D., Garmo, H., Häggström, C., Holmberg, L., . . . Adolfsson, J. (2019). Chronic inflammatory diseases, anti-inflammatory medications and risk of prostate cancer: a population-based case-control study. BMC Cancer, 19, Article ID 612.
Open this publication in new window or tab >>Chronic inflammatory diseases, anti-inflammatory medications and risk of prostate cancer: a population-based case-control study
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2019 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 19, article id 612Article in journal (Refereed) Published
Abstract [en]

Background: Whether chronic inflammation increases prostate cancer risk remains unclear. This study investigated whether chronic inflammatory diseases (CID) or anti-inflammatory medication use (AIM) were associated with prostate cancer risk.

Methods: Fifty-five thousand nine hundred thirty-seven cases (all prostate cancer, 2007-2012) and 279,618 age-matched controls were selected from the Prostate Cancer Database Sweden. CIDs and AIMs was determined from national patient and drug registers. Associations were investigated using conditional logistic regression, including for disease/drug subtypes and exposure length/dose.

Results: Men with a history of any CID had slightly increased risk of any prostate cancer diagnosis (OR: 1.08; 95%CI: 1.04-1.12) but not unfavourable' (high-risk or advanced) prostate cancer. Generally, risk of prostate cancer was highest for shorter exposure times. However, a positive association was observed for asthma >5years before prostate cancer diagnosis (OR: 1.21; 95%CI: 1.05-1.40). Risk of prostate cancer was increased with prior use of any AIMs (OR: 1.26; 95%CI: 1.24-1.29). A positive trend with increasing cumulative dose was only observed for inhaled glucocorticoids (p<0.011).

Conclusion: Detection bias most likely explains the elevated risk of prostate cancer with prior history of CIDs or use of AIMs, given the higher risk immediately after first CID event and lack of dose response. However, findings for length of time with asthma and dose of inhaled glucocorticoids suggest that asthma may increase risk of prostate cancer through other pathways.

Place, publisher, year, edition, pages
BMC, 2019
Keywords
Prostate cancer, Chronic inflammatory disease, Autoimmune disease, Anti-inflammatory medication
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-390092 (URN)10.1186/s12885-019-5846-3 (DOI)000472477600005 ()31226970 (PubMedID)
Funder
Swedish Cancer Society, 2013/472
Available from: 2019-08-05 Created: 2019-08-05 Last updated: 2019-08-05Bibliographically approved
Cazzaniga, W., Garmo, H., Robinson, D., Holmberg, L., Bill-Axelson, A. & Stattin, P. (2019). Mortality after radical prostatectomy in a matched contemporary cohort in Sweden compared to the Scandinavian Prostate Cancer Group 4 (SPCG-4) study. BJU International, 123(3), 421-428
Open this publication in new window or tab >>Mortality after radical prostatectomy in a matched contemporary cohort in Sweden compared to the Scandinavian Prostate Cancer Group 4 (SPCG-4) study
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2019 (English)In: BJU International, ISSN 1464-4096, E-ISSN 1464-410X, Vol. 123, no 3, p. 421-428Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To investigate if results in terms of absolute risk in mature randomised trials are relevant for contemporary decision-making. To do so, we compared the outcome for men in the radical prostatectomy (RP) arm of the Scandinavian Prostate Cancer Group Study number 4 (SPCG-4) randomised trial with matched men treated in a contemporary era before and after compensation for the grade migration and grade inflation that have occurred since the 1980s.

PATIENTS AND METHODS: A propensity score-matched analysis of prostate cancer mortality and all-cause mortality in the SPCG-4 and matched men in the National Prostate Cancer Register (NPCR) of Sweden treated in 1998-2006 was conducted. Cumulative incidence of prostate cancer mortality and all-cause mortality was calculated. Cox proportional hazards regression analyses were used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) for a matching on original Gleason Grade Groups (GGG) and second, matching with GGG increased one unit for men in the NPCR.

RESULTS: Matched men in the NPCR treated in 2005-2006 had half the risk of prostate cancer mortality compared to men in the SPCG-4 (HR 0.46, 95% CI 0.19-1.14). In analysis of men matched on an upgraded GGG in the NPCR, this difference was mitigated (HR 0.73, 95% CI 0.36-1.47).

CONCLUSIONS: Outcomes after RP for men in the SPCG-4 cannot be directly applied to men in the current era, mainly due to grade inflation and grade migration. However, by compensating for changes in grading, similar outcomes after RP were seen in the SPCG-4 and NPCR. In order to compare historical trials with current treatments, data on temporal changes in detection, diagnostics, and treatment have to be accounted for.

Keywords
Gleason Grade Groups, mortality, National Prostate Cancer Register of Sweden, Scandinavian Prostate Cancer Group Study Number 4, #PCSM, #ProstateCancer
National Category
Medical and Health Sciences Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-381179 (URN)10.1111/bju.14563 (DOI)000460173100013 ()30253031 (PubMedID)
Funder
Swedish Research Council, 2017-00847
Available from: 2019-04-05 Created: 2019-04-05 Last updated: 2019-04-12Bibliographically approved
Bill-Axelson, A., Holmberg, L. & Garmo, H. (2019). Radical Surgery or Watchful Waiting in Prostate Cancer Reply [Letter to the editor]. New England Journal of Medicine, 380(11), 1084-1084
Open this publication in new window or tab >>Radical Surgery or Watchful Waiting in Prostate Cancer Reply
2019 (English)In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 380, no 11, p. 1084-1084Article in journal, Letter (Other academic) Published
National Category
Cancer and Oncology General Practice
Identifiers
urn:nbn:se:uu:diva-380667 (URN)10.1056/NEJMc1900410 (DOI)000461210000019 ()30865809 (PubMedID)
Available from: 2019-04-01 Created: 2019-04-01 Last updated: 2019-04-01Bibliographically approved
Häggström, C., Garmo, H., de Luna, X., Van Hemelrijck, M., Söderkvist, K., Aljabery, F., . . . Holmberg, L. (2019). Survival after radiotherapy versus radical cystectomy for primary muscle-invasive bladder cancer: A Swedish nationwide population-based cohort study. Cancer Medicine, 8(5), 2196-2204
Open this publication in new window or tab >>Survival after radiotherapy versus radical cystectomy for primary muscle-invasive bladder cancer: A Swedish nationwide population-based cohort study
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2019 (English)In: Cancer Medicine, ISSN 2045-7634, E-ISSN 2045-7634, Vol. 8, no 5, p. 2196-2204Article in journal (Refereed) Published
Abstract [en]

Background: Studies of survival comparing radical cystectomy (RC) and radiotherapy for muscle-invasive bladder cancer have provided inconsistent results and have methodological limitations. The aim of the study was to investigate risk of death after radiotherapy as compared to RC.

Methods: We selected patients with muscle-invasive urothelial carcinoma without distant metastases, treated with radiotherapy or RC from 1997 to 2014 in the Bladder Cancer Data Base Sweden (BladderBaSe) and estimated absolute and relative risk of bladder cancer death and all-cause death. In a group of patients, theoretically eligible for a trial comparing radiotherapy and RC, we calculated risk difference in an instrumental variable analysis. We have not investigated chemoradiotherapy as this treatment was not used in the study time period.

Results: The study included 3 309 patients, of those 17% were treated with radiotherapy and 83% with RC. Patients treated with radiotherapy were older, had more advanced comorbidity, and had a higher risk of death as compared to patients treated with RC (relative risks of 1.5-1.6). In the "trial population," all-cause death risk difference was 6 per 100 patients lower after radiotherapy at 5 years of follow-up, 95% confidence interval -41 to 29.

Conclusion(s): Patient selection between the treatments make it difficult to evaluate results from conventionally adjusted and propensity-score matched survival analysis. When taking into account unmeasured confounding by instrumental variable analysis, no differences in survival was found between the treatments for a selected group of patients. Further clinical studies are needed to characterize this group of patients, which can serve as a basis for future comparison studies for treatment recommendations.

Place, publisher, year, edition, pages
WILEY, 2019
Keywords
bladder cancer, muscle-invasive, radical cystectomy, radiotherapy, urothelial carcinoma
National Category
Cancer and Oncology Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-387973 (URN)10.1002/cam4.2126 (DOI)000469272500024 ()30938068 (PubMedID)
Funder
Swedish Cancer Society, CAN 2013/472
Available from: 2019-06-27 Created: 2019-06-27 Last updated: 2019-06-27Bibliographically approved
Wennstig, A.-K., Garmo, H., Isacsson, U., Gagliardi, G., Rintelä, N., Lagerqvist, B., . . . Nilsson, G. (2019). The relationship between radiation doses to coronary arteries and location of coronary stenosis requiring intervention in breast cancer survivors. Radiation Oncology, 14, Article ID 40.
Open this publication in new window or tab >>The relationship between radiation doses to coronary arteries and location of coronary stenosis requiring intervention in breast cancer survivors
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2019 (English)In: Radiation Oncology, ISSN 1748-717X, E-ISSN 1748-717X, Vol. 14, article id 40Article in journal (Refereed) Published
Abstract [en]

Background: To assess the relationship between radiation doses to the coronary arteries (CAs) and location of a coronary stenosis that required intervention after three-dimensional conformal radiotherapy (3DCRT) for breast cancer (BC).

Methods: The study population consisted of 182 women treated for BC in Sweden between 1992 and 2012. All women received 3DCRT and subsequently underwent coronary angiography due to a suspected coronary event. CA segments were delineated in the patient's original planning-CT and radiation doses were recalculated based on the dose distribution of the original radiotherapy (RT) plan. The location of the CA stenosis that required intervention was identified from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Logistic regression analysis was used to assess the relationship between CA radiation doses and risk of a later coronary intervention at this specific location.

Results: The odds ratio (OR) varied by radiation dose to the mid left anterior descending artery (LAD) (p=0.005). Women receiving mean doses of 1-5 Gray (Gy) to the mid LAD had an adjusted OR of 0.90 (95% CI 0.47-1.74) for a later coronary intervention compared to women receiving mean doses of 0-1Gy to the mid LAD. In women receiving mean doses of 5-20Gy to the mid LAD, an adjusted OR of 1.24 (95% CI 0.52-2.95) was observed, which increased to an OR of 5.23 (95% CI 2.01-13.6) for mean doses over 20Gy, when compared to women receiving mean doses of 0-1Gy to the mid LAD.

Conclusions: In women receiving conventional 3DCRT for BC between 1992 and 2012, radiation doses to the LAD remained high and were associated with an increased requirement of coronary intervention in mid LAD. The results support that the LAD radiation dose should be considered in RT treatment planning and that the dose should be kept as low as possible. Minimising the dose to LAD is expected to diminish the risk of later radiation-induced stenosis.

Place, publisher, year, edition, pages
BMC, 2019
Keywords
Breast cancer, Radiotherapy, Radiation doses, 3DCRT, Coronary stenosis, Left anterior descending artery
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-379891 (URN)10.1186/s13014-019-1242-z (DOI)000460794000002 ()30845947 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2019-03-25 Created: 2019-03-25 Last updated: 2019-03-25Bibliographically approved
Crawley, D., Chamberlain, F., Garmo, H., Rudman, S., Zethelius, B., Holmberg, L., . . . Van Hemelrijck, M. (2018). A systematic review of the literature exploring the interplay between prostate cancer and type two diabetes mellitus. ecancermedicalscience, 12, Article ID 802.
Open this publication in new window or tab >>A systematic review of the literature exploring the interplay between prostate cancer and type two diabetes mellitus
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2018 (English)In: ecancermedicalscience, ISSN 1754-6605, E-ISSN 1754-6605, Vol. 12, article id 802Article, review/survey (Refereed) Published
Abstract [en]

Prostate cancer (PCa) and type two diabetes mellitus (T2DM) are both increasing prevalent conditions and often occur concurrently. However, the relationship between the two is more complex than just two prevalent conditions co-existing. This review systematically explores the literature around the interplay between the two conditions. It covers the impact of pre-existing T2DM on PCa incidence, grade and stage, as well as exploring the impact of T2DM on PCa outcomes and mortality and the interaction between T2DM and PCa treatments.

Keywords
type two diabetes, prostate cancer, review
National Category
Cancer and Oncology Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-350200 (URN)10.3332/ecancer.2018.802 (DOI)000423854500001 ()29456619 (PubMedID)
Available from: 2018-05-08 Created: 2018-05-08 Last updated: 2018-05-08Bibliographically approved
Wärnberg, F., Garmo, H., Folkvaljon, Y., Holmberg, L., Karlsson, P., Sandelin, K., . . . Bremer, T. (2018). Abstract GS5-08: A validation of DCIS biological risk profile in a randomised study for radiation therapy with 20 year follow-up (SweDCIS). Paper presented at San Antonio Breast Cancer Symposium, DEC 05-09, 2017, San Antonio, TX. Cancer Research, 78(4)
Open this publication in new window or tab >>Abstract GS5-08: A validation of DCIS biological risk profile in a randomised study for radiation therapy with 20 year follow-up (SweDCIS)
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2018 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 78, no 4Article in journal, Meeting abstract (Other academic) Published
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-351602 (URN)10.1158/1538-7445.SABCS17-GS5-08 (DOI)000425489400036 ()
Conference
San Antonio Breast Cancer Symposium, DEC 05-09, 2017, San Antonio, TX
Note

Wos title: A validation of DCIS biological risk profile in a randomised study for radiation therapy with 20 year follow-up (SweDCIS)

Supplement: S

Meeting Abstract: GS5-08

Available from: 2018-05-29 Created: 2018-05-29 Last updated: 2018-09-12Bibliographically approved
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