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Holmberg, Lars
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Publications (10 of 222) 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
Åström, L., Sandin, F. & Holmberg, L. (2018). Good Prognosis following a PSA Bounce after High Dose Rate Brachytherapy and External Radiotherapy in Prostate Cancer. Radiotherapy and Oncology, 129(3), 561-566
Open this publication in new window or tab >>Good Prognosis following a PSA Bounce after High Dose Rate Brachytherapy and External Radiotherapy in Prostate Cancer
2018 (English)In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 129, no 3, p. 561-566Article in journal (Refereed) Published
Abstract [en]

Background

PSA kinetics after curative radiotherapy for prostate cancer is an important part of the posttreatment evaluation. We analysed PSA bounce occurrence after combined high dose rate brachytherapy (HDR-BT) and external radiotherapy (ERT).

Material & methods

We analysed 623 patients treated from 1995 to 2008. The median age was 66 years (47-79). The median initial PSA was 12 ng/ml (0.1-224). Neoadjuvant endocrine therapy was given to 429 patients. ERT was given with 2 Gy fractions to 50 Gy and HDR-BT in two 10 Gy fractions. The median follow-up was 11 years (range 2-266 months). PSA bounce was defined as a temporary rise in PSA >0.2 ng/ml. PSA failure was defined according to the Phoenix definition.

Results

PSA bounce occurred in 159 patients (26%), where 56 patients had a bounce amplitude >2 ng/ml and 31 patients had multiple bounces. Median time to bounce peak was 15 (3-103) months with a median bounce value of 1.5 (0.3-12) ng/ml. Younger age and lower Gleason scores were associated with PSA bounce. In a Cox regression analysis with PSA bounce as a time-dependent covariate and adjusted for other prognostic factors, PSA bounce was associated with a lower risk for PSA failure (HR=0.42; 95% confidence interval 0.26-0.70).

Conclusion

PSA bounce after HDR-BT combined with ERT is common and associated with a good prognosis. As the relapse risk after an early bounce is very low, the findings should alert clinicians not to initiate salvage treatment too early. Research in prospective identification of PSA bounce is clinically relevant.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-347416 (URN)10.1016/j.radonc.2018.08.011 (DOI)000452272800023 ()30193693 (PubMedID)
Note

Title in thesis list of papers: Good Prognosis following a PSA Bounce after High Dose Rate Brachytherapy with External Radiotherapy in Prostate Cancer

Available from: 2018-03-31 Created: 2018-03-31 Last updated: 2019-01-09Bibliographically 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
Wickberg, A., Magnuson, A., Holmberg, L., Adami, H.-O. & Liljegren, G. (2018). Influence of the subtype on local recurrence risk of breast cancer with or without radiation therapy. Breast, 42, 54-60
Open this publication in new window or tab >>Influence of the subtype on local recurrence risk of breast cancer with or without radiation therapy
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2018 (English)In: Breast, ISSN 0960-9776, E-ISSN 1532-3080, Vol. 42, p. 54-60Article in journal (Refereed) Published
Abstract [en]

Purpose: To investigate if intrinsic subtypes of breast cancer predict different risks of ipsilateral breast tumor recurrence (IBTR) following breast-conserving surgery (BCS) with and without postoperative radiation therapy. Patients and methods: We randomized 381 women with a unifocal T1N0M0 breast cancer to BCS alone (197 women) or BCS plus postoperative radiation therapy (XRT) (184 women). All available histopathological material was re-analyzed with modern immunohistochemical methods (223 women). After 20 years of complete follow-up we analyzed the risk of IBTR by intrinsic breast cancer subtypes (luminal A, luminal B/HER2-negative, luminal B/HER2-positive, HER2-positive and triple negative). We used Cox regression analyses to estimate hazard ratios (HR) with 95% confidence intervals (CI). Results: In a multivariate analysis the luminal B/HER2-negative subtype, compared with the luminal A subtype, was associated with a higher risk of IBTR overall (HR 3.04; 95% CI 1.38-6.71) and in both the XRT-group (HR 5.08 95% CI 1.31-19.7) and the non-XRT-group (HR 2.58 95%CI 1.07-6.20); (p for interaction 0.37). The risk of IBTR in the XRT- and non-XRT group, stratified by intrinsic subtype, revealed an absolute risk difference at 20 years to the benefit of XRT of 14% (95% CI 1.0%-26%) for luminal A, 17% (95% CI -6.0% to 39%) for luminal B/HER2 negative and 22% (95% CI -7.0-51%) for the high-risk group. Conclusions: Among breast cancer patients treated with BCS, the luminal B/HER2-negative subtype predicts an about 3-fold higher risk for IBTR compared to other intrinsic subtypes independent of postoperative radiation therapy. (C) 2018 Elsevier Ltd. All rights reserved.

Place, publisher, year, edition, pages
CHURCHILL LIVINGSTONE, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-369386 (URN)10.1016/j.breast.2018.08.097 (DOI)000448315600010 ()30176553 (PubMedID)
Available from: 2019-01-15 Created: 2019-01-15 Last updated: 2019-01-15Bibliographically approved
Birgegård, G., Folkvaljon, F., Garmo, H., Holmberg, L., Besses, C., Griesshammer, M., . . . Harrison, C. N. (2018). Leukemic transformation and second cancers in 3649 patients with high-risk essential thrombocythemia in the EXELS study. Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, 74, 105-109
Open this publication in new window or tab >>Leukemic transformation and second cancers in 3649 patients with high-risk essential thrombocythemia in the EXELS study
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2018 (English)In: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 74, p. 105-109Article in journal (Refereed) Published
Abstract [en]

EXELS, a post-marketing observational study, is the largest prospective study of high-risk essential thrombocythemia (ET) patients, with an observation time of 5 years. EXELS found higher event rates of acute leukemia transformation in patients treated with hydroxycarbamide (HC). In the current analysis, we report age-adjusted rates of malignant transformation from 3460 EXELS patients exposed to HC, anagrelide (ANA), or both. At registration, 481 patients had ANA treatment without HC exposure, 2305 had HC without ANA exposure, and 674 had been exposed to both. Standard incidence ratios (SIRs) were calculated using data from the Cancer Incidence in Five Continents database to account for differences in age-, gender-, and country-specific background rates. SIRs for acute myelogenous leukemia (AML) were high in ET patients. SIRs for AML were high in HC-treated patients, but AML was rare in ANA-treated patients; no cases of AML were found in patients only treated with ANA. No statistically significant difference was seen between SIRs for ANA and HC treatment for AML or skin cancer. SIRs for other cancers were similar in the HC and ANA groups and close to 1, indicating little difference in risk. Although statistically inconclusive, this study strengthens concerns regarding possible leukemogenic risk with HC treatment. (NCT00202644)

Keywords
Acute myelogenous leukemia, Malignant transformation, Anagrelide, Hydroxycarbamide
National Category
Cancer and Oncology Hematology
Identifiers
urn:nbn:se:uu:diva-369595 (URN)10.1016/j.leukres.2018.10.006 (DOI)000449112000017 ()30368038 (PubMedID)
Available from: 2018-12-19 Created: 2018-12-19 Last updated: 2018-12-19Bibliographically approved
Bill-Axelson, A., Holmberg, L., Garmo, H., Taari, K., Busch, C., Nordling, S., . . . Johansson, J.-E. (2018). Radical Prostatectomy or Watchful Waiting in Prostate Cancer: 29-Year Follow-up. New England Journal of Medicine, 379(24), 2319-2329
Open this publication in new window or tab >>Radical Prostatectomy or Watchful Waiting in Prostate Cancer: 29-Year Follow-up
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2018 (English)In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 379, no 24, p. 2319-2329Article in journal (Refereed) Published
Abstract [en]

BACKGROUND Radical prostatectomy reduces mortality among men with clinically detected localized prostate cancer, but evidence from randomized trials with long-term followup is sparse.

METHODS We randomly assigned 695 men with localized prostate cancer to watchful waiting or radical prostatectomy from October 1989 through February 1999 and collected follow-up data through 2017. Cumulative incidence and relative risks with 95% confidence intervals for death from any cause, death from prostate cancer, and metastasis were estimated in intention-to-treat and per-protocol analyses, and numbers of years of life gained were estimated. We evaluated the prognostic value of histopathological measures with a Cox proportional-hazards model.

RESULTS By December 31, 2017, a total of 261 of the 347 men in the radical-prostatectomy group and 292 of the 348 men in the watchful-waiting group had died; 71 deaths in the radical-prostatectomy group and 110 in the watchful-waiting group were due to prostate cancer (relative risk, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001; absolute difference in risk, 11.7 percentage points; 95% CI, 5.2 to 18.2). The number needed to treat to avert one death from any cause was 8.4. At 23 years, a mean of 2.9 extra years of life were gained with radical prostatectomy. Among the men who underwent radical prostatectomy, extracapsular extension was associated with a risk of death from prostate cancer that was 5 times as high as that among men without extracapsular extension, and a Gleason score higher than 7 was associated with a risk that was 10 times as high as that with a score of 6 or lower (scores range from 2 to 10, with higher scores indicating more aggressive cancer).

CONCLUSIONS Men with clinically detected, localized prostate cancer and a long life expectancy benefited from radical prostatectomy, with a mean of 2.9 years of life gained. A high Gleason score and the presence of extracapsular extension in the radical prostatectomy specimens were highly predictive of death from prostate cancer.

National Category
Urology and Nephrology General Practice
Identifiers
urn:nbn:se:uu:diva-372932 (URN)10.1056/NEJMoa1807801 (DOI)000452872600007 ()30575473 (PubMedID)
Funder
Swedish Cancer Society, 07 05 12 CAN 2014/1275The Karolinska Institutet's Research Foundation
Available from: 2019-01-10 Created: 2019-01-10 Last updated: 2019-01-10Bibliographically approved
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