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Holmberg, Lars
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Publications (10 of 215) Show all publications
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
Pettersson, A., Robinson, D., Garmo, H., Holmberg, L. & Stattin, P. (2018). Age at diagnosis and prostate cancer treatment and prognosis: a population-based cohort study.. Annals of Oncology, 29(2), 377-385
Open this publication in new window or tab >>Age at diagnosis and prostate cancer treatment and prognosis: a population-based cohort study.
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2018 (English)In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 29, no 2, p. 377-385Article in journal (Refereed) Published
Abstract [en]

Background: Old age at prostate cancer diagnosis has been associated with poor prognosis in several studies. We aimed to investigate the association between age at diagnosis and prognosis, and if it is independent of tumor characteristics, primary treatment, year of diagnosis, mode of detection and comorbidity.

Patients and methods: We conducted a nation-wide cohort study including 121,392 Swedish men aged 55-95 years in Prostate Cancer data Base Sweden (PCBaSe) 3.0 diagnosed with prostate cancer in 1998-2012 and followed for prostate cancer death through 2014. Data were available on age, stage, grade, PSA-level, mode of detection, comorbidity, educational level and primary treatment. We used Cox regression to calculate hazard ratios (HR) and 95% confidence intervals (CIs).

Results: With increasing age at diagnosis, men had more comorbidity, fewer PSA detected cancers, more advanced cancers and were less often treated with curative intent. Among men with high-risk or regionally metastatic disease, the proportion of men with unknown M stage was higher among old men versus young men. During a follow-up of 751,000 person-years, 23,649 men died of prostate cancer. In multivariable Cox-regression analyses stratified by treatment, old age at diagnosis was associated with poorer prognosis among men treated with deferred treatment (HRage 85+ vs. 60-64: 7.19; 95% CI: 5.61-9.20), androgen deprivation therapy (HRage 85+ vs. 60-64: 1.72; 95% CI: 1.61-1.84) or radical prostatectomy (HRage 75+ vs. 60-64: 2.20; 95% CI: 1.01-4.77), but not radiotherapy (HRage 75+ vs. 60-64: 1.08; 95% CI: 0.76-1.53).

Conclusion: Our findings argue against a strong inherent effect of age on risk of prostate cancer death, but indicate that in current clinical practice, old men with prostate cancer receive insufficient diagnostic work-up and subsequent curative treatment.

Keywords
Age at diagnosis, Cohort study, Prognosis, Prostate cancer, Treatment
National Category
Cancer and Oncology Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-336231 (URN)10.1093/annonc/mdx742 (DOI)29161337 (PubMedID)
Available from: 2017-12-13 Created: 2017-12-13 Last updated: 2018-04-26Bibliographically approved
Grönberg, M., Nilsson, C., Markholm, I., Hedenfalk, I., Blomqvist, C., Holmberg, L., . . . Fjällskog, M.-L. (2018). Ghrelin expression is associated with a favorable outcome in male breast cancer. Scientific Reports, 8, Article ID 13586.
Open this publication in new window or tab >>Ghrelin expression is associated with a favorable outcome in male breast cancer
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 13586Article in journal (Refereed) Published
Abstract [en]

Ghrelin and obestatin are two gastrointestinal peptides, derived from a common precursor. Expression of both peptides have been found in breast cancer tissue and ghrelin has been associated with breast cancer development. Ghrelin expression is associated with longer survival in women diagnosed with invasive and node negative breast cancer. The clinical implications of the peptide expression in male breast cancer are unclear. The aim of this study was to investigate the role and potential clinical value of ghrelin and obestatin in male breast cancer. A tissue microarray of invasive male breast cancer specimens from 197 patients was immunostained with antibodies versus the two peptides. The expression of the peptides was correlated to previously known prognostic factors in breast cancer and to the outcome. No strong correlations were found between ghrelin or obestatin expression and other known prognostic factors. Only ghrelin expression was statistically significantly correlated to breast cancer-specific survival (HR 0.39, 95% CI 0.18-0.83) in univariate analyses and in multivariate models, adjusted for tumor size and node status (HR 0.38, 95% CI 0.17-0.87). HR for obestatin was 0.38 (95% CI 0.11-1.24). Ghrelin is a potential prognostic factor for breast cancer death in male breast cancer. Patients with tumors expressing ghrelin have a 2.5-fold lower risk for breast cancer death than those lacking ghrelin expression. Drugs targeting ghrelin are currently being investigated in clinical studies treating metabolic or nutritional disorders. Ghrelin should be further evaluated in forthcoming studies as a prognostic marker with the aim to be included in decision algorithms.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-365298 (URN)10.1038/s41598-018-31783-x (DOI)000444278400020 ()30206250 (PubMedID)
Funder
Swedish Cancer Society, CAN 2014/558Swedish Cancer Society, CAN 2011/461The Breast Cancer FoundationErik, Karin och Gösta Selanders Foundation
Available from: 2018-11-13 Created: 2018-11-13 Last updated: 2018-11-13Bibliographically approved
Bosco, C., Garmo, H., Hammar, N., Walldius, G., Jungner, I., Malmström, H., . . . Van Hemelrijck, M. (2018). Glucose, lipids and gamma-glutamyl transferase measured before prostate cancer diagnosis and secondly diagnosed primary tumours: a prospective study in the Swedish AMORIS cohort. BMC Cancer, 18, Article ID 205.
Open this publication in new window or tab >>Glucose, lipids and gamma-glutamyl transferase measured before prostate cancer diagnosis and secondly diagnosed primary tumours: a prospective study in the Swedish AMORIS cohort
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2018 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 18, article id 205Article in journal (Refereed) Published
Abstract [en]

Background: Improvements in detection and treatment of prostate cancer (PCa) translate into more men living with PCa, who are therefore potentially at risk of a secondly diagnosed primary tumour (SDPTs). Little is known about potential biochemical mechanisms linking PCa with the occurrence of SDPTs. The current study aims to investigate serum biomarkers of glucose and lipid metabolism and gamma-glutamyl transferase (GGT) measured prior to PCa diagnosis and their association with the occurrence of SDPTS.

Methods: From the Swedish AMORIS cohort, we selected all men diagnosed with PCa between 1996 and 2011, with at least one of the five biomarkers of interest (glucose, fructosamine, triglycerides, total cholesterol (TC), GGT) measured on average 16 years before PCa diagnosis (n = 10,791). Multivariate Cox proportional hazards models were used to determine hazard ratios (HR) for risk of SDPTs (overall and subtypes) by levels of the five biomarkers. Effect modification of treatment was assessed.

Results: 811 SDPTS were diagnosed during a median follow-up time of 5 years. Elevated levels of triglycerides (HR: 1.37, 95% CI: 1.17-1.60), TC (HR: 1.22, 95% CI: 1.04-1.42) and GGT (HR: 1.32, 95% CI: 1.02-1.71) were associated with an increased risk of SDPTs. Risk of SDPTs subtypes varied by biomarkers.

Conclusion: Elevated levels of biomarkers of lipid metabolism and GGT measured prior to PCa diagnosis were associated with an increased risk of SDPTs, suggesting a potential common biochemical background for development of PCa and SDPTs.

Place, publisher, year, edition, pages
BIOMED CENTRAL LTD, 2018
Keywords
Prostate cancer, Second primary tumours, Triglycerides, Gamma-glutamyl transferase, Glucose, Total cholesterol
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-349350 (URN)10.1186/s12885-018-4111-5 (DOI)000425517700006 ()29463235 (PubMedID)
Funder
Swedish Cancer SocietyForte, Swedish Research Council for Health, Working Life and Welfare
Available from: 2018-05-02 Created: 2018-05-02 Last updated: 2018-05-02Bibliographically approved
Häggström, C., Van Hemelrijck, M., Garmo, H., Robinson, D., Stattin, P., Rowley, M., . . . Holmberg, L. (2018). Heterogeneity in risk of prostate cancer: A Swedish population-based cohort study of competing risks and Type 2 diabetes mellitus. International Journal of Cancer, 143(8), 1868-1875
Open this publication in new window or tab >>Heterogeneity in risk of prostate cancer: A Swedish population-based cohort study of competing risks and Type 2 diabetes mellitus
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2018 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 143, no 8, p. 1868-1875Article in journal (Refereed) Published
Abstract [en]

Most previous studies of prostate cancer have not taken into account that men in the studied populations are also at risk of competing event, and that these men may have different susceptibility to prostate cancer risk. The aim of our study was to investigate heterogeneity in risk of prostate cancer, using a recently developed latent class regression method for competing risks. We further aimed to elucidate the association between Type 2 diabetes mellitus (T2DM) and prostate cancer risk, and to compare the results with conventional methods for survival analysis. We analysed the risk of prostate cancer in 126,482 men from the comparison cohort of the Prostate Cancer Data base Sweden (PCBaSe) 3.0. During a mean follow-up of 6years 6,036 men were diagnosed with prostate cancer and 22,393 men died. We detected heterogeneity in risk of prostate cancer with two distinct latent classes in the study population. The smaller class included 9% of the study population in which men had a higher risk of prostate cancer and the risk was stronger associated with class membership than any of the covariates included in the study. Moreover, we found no association between T2DM and risk of prostate cancer after removal of the effect of informative censoring due to competing risks. The recently developed latent class for competing risks method could be used to provide new insights in precision medicine with the target to classify individuals regarding different susceptibility to a particular disease, reaction to a risk factor or response to treatment.

Keywords
survival analysis, competing risks, latent class, prostate cancer, Type 2 diabetes mellitus
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-364127 (URN)10.1002/ijc.31587 (DOI)000443942800005 ()29744858 (PubMedID)
Funder
Swedish Cancer Society, 2013/472
Available from: 2018-11-05 Created: 2018-11-05 Last updated: 2018-11-05Bibliographically approved
Pettersson, A., Robinson, D., Garmo, H., Holmberg, L. & Stattin, P. (2018). Reply to the letter to the editor 'Age at diagnosis and prognosis among prostate cancer patients treated with radiotherapy: evidenced from three independent cohort studies' by X. Dong, G. Ma and F. Chen [Letter to the editor]. Annals of Oncology, 29(9), 2020-2021
Open this publication in new window or tab >>Reply to the letter to the editor 'Age at diagnosis and prognosis among prostate cancer patients treated with radiotherapy: evidenced from three independent cohort studies' by X. Dong, G. Ma and F. Chen
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2018 (English)In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 29, no 9, p. 2020-2021Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
Oxford University Press, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-368380 (URN)10.1093/annonc/mdy236 (DOI)000446087800023 ()29992285 (PubMedID)
Available from: 2018-12-06 Created: 2018-12-06 Last updated: 2018-12-06Bibliographically approved
Wadsten, C., Wennstig, A.-K., Garmo, H., Nilsson, G., Blomqvist, C., Holmberg, L., . . . Sund, M. (2018). Risk of ischemic heart disease after radiotherapy for ductal carcinoma in situ. Breast Cancer Research and Treatment, 171(1), 95-101
Open this publication in new window or tab >>Risk of ischemic heart disease after radiotherapy for ductal carcinoma in situ
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2018 (English)In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 171, no 1, p. 95-101Article in journal (Refereed) Published
Abstract [en]

The use of adjuvant radiotherapy (RT) in the management of ductal carcinoma in situ (DCIS) is increasing. Left-sided breast irradiation may involve exposure of the heart to ionising radiation, increasing the risk of ischemic heart disease (IHD). We examined the incidence of IHD in a population-based cohort of women with DCIS. The Breast Cancer DataBase Sweden (BCBase) cohort includes women registered with invasive and in situ breast cancers 1992-2012 and age-matched women without a history of breast cancer. In this analysis, 6270 women with DCIS and a comparison cohort of 31,257 women were included. Through linkage with population-based registers, data on comorbidity, socioeconomic status and incidence of IHD was obtained. Hazard ratios (HR) for IHD with 95% confidence intervals (CI) were analysed. Median follow-up time was 8.8 years. The risk of IHD was not increased for women with DCIS versus women in the comparison cohort (HR 0.93; 95% CI 0.82-1.06), after treatment with radiotherapy versus surgery alone (HR 0.77; 95% CI 0.60-0.98) or when analysing RT by laterality (HR 0.85; 95% CI 0.53-1.37 for left-sided versus right-sided RT). The risk of IHD was lower for women with DCIS allocated to RT compared to non-irradiated women and to the comparison cohort, probably due to patient selection. Comparison of RT by laterality did not show any over-risk for irradiation of the left breast.

Place, publisher, year, edition, pages
SPRINGER, 2018
Keywords
Ductal carcinoma in situ, Radiotherapy, Ischemic heart disease
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-361504 (URN)10.1007/s10549-018-4803-1 (DOI)000438656200010 ()29730730 (PubMedID)
Funder
The Breast Cancer FoundationVästerbotten County Council
Available from: 2018-09-25 Created: 2018-09-25 Last updated: 2018-09-25Bibliographically approved
Wennstig, A. K., Garmo, H., Isacsson, U., Gagliardi, G., Rintela, N., Lagerqvist, B., . . . Nilsson, G. (2018). The relationship between radiation doses to coronary arteries and later intervention requiring coronary stenosis in breast cancer. Paper presented at 11th European Breast Cancer Conference (EBCC), MAR 21-23, 2018, Barcelona, SPAIN. European Journal of Cancer, 92, S61-S62
Open this publication in new window or tab >>The relationship between radiation doses to coronary arteries and later intervention requiring coronary stenosis in breast cancer
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2018 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 92, p. S61-S62Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-357181 (URN)000429103100150 ()
Conference
11th European Breast Cancer Conference (EBCC), MAR 21-23, 2018, Barcelona, SPAIN
Available from: 2018-08-14 Created: 2018-08-14 Last updated: 2018-08-14Bibliographically approved
Åström, L., Grusell, E., Sandin, F., Turesson, I. & Holmberg, L. (2018). Two decades of high dose rate brachytherapy with external beam radiotherapy for prostate cancer. Radiotherapy and Oncology, 127(1), 81-87
Open this publication in new window or tab >>Two decades of high dose rate brachytherapy with external beam radiotherapy for prostate cancer
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2018 (English)In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 127, no 1, p. 81-87Article in journal (Refereed) Published
Abstract [en]

Background: High-dose-rate brachytherapy (HDR-BT) has optimal prerequisites in radiotherapy of prostate cancer (PC) with a conformal dose distribution and high doses per fraction giving a biological dose escalation. We report the outcome after HDR-BT and external beam radiotherapy (EBRT) after 20 years of experience.

Material and methods: The study includes 623 patients, median age of 66 years, treated from 1995 to 2008 and a median follow up of 11 years (range 2–266 months). Androgen deprivation therapy was given to 429 patients (69%). The HDR-BT was given with two 10 Gy fractions and the EBRT with 2 Gy fractions to 50 Gy.

Results: The 10-year PC-specific survival was 100%, 92%, 91%, and 75% for low-, intermediate-, high- and very high-risk patients respectively, and the 10-year probability of PSA relapse was 0%, 21%, 33%, and 65% respectively. The 10-year actuarial prevalence for ≥grade 2 GU- and GI-toxicities were 28% and 12% respectively and for ≥grade 3, 4% and 1% respectively. Urethral stricture was the most frequent GU complication with a 10-year actuarial incidence of 10%. Treatment without dose constraints for the urethra conferred a higher incidence 18%, compared to 5% after 2003 (p < 0.001). Sixteen patients experienced grade 4 GU toxicity, of which 13 were treated before 2003. No grade 4 rectal toxicity was seen.

Conclusion: The combination of EBRT and HDR-BT with adequate dose constraints to risk organs provides satisfactory long-term tumour control even in high-risk patients. GI toxicity stabilised but GU toxicity progressed during the 10-year follow up.

Keywords
Brachytherapy, High dose rate, Prostate cancer, Radiotherapy
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-347411 (URN)10.1016/j.radonc.2017.12.025 (DOI)000433102000013 ()29496280 (PubMedID)
Available from: 2018-03-31 Created: 2018-03-31 Last updated: 2018-08-24Bibliographically approved
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