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Häggman, Michael
Alternative names
Publications (10 of 22) Show all publications
Glimelius, B., Melin, B., Enblad, G., Alafuzoff, I., Beskow, A. H., Ahlström, H., . . . Sjöblom, T. (2018). U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.. Acta Oncologica, 57(2), 187-194
Open this publication in new window or tab >>U-CAN: a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.
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2018 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 2, p. 187-194Article in journal (Refereed) Published
Abstract [en]

Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.

Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.

Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.

Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.

National Category
Cancer and Oncology Urology and Nephrology
Identifiers
urn:nbn:se:uu:diva-325565 (URN)10.1080/0284186X.2017.1337926 (DOI)000423473200003 ()28631533 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2017-06-26 Created: 2017-06-26 Last updated: 2018-03-09Bibliographically approved
von Below, C., Wassberg, C., Norberg, M., Tolf, A., Kullberg, J., Ladjevardi, S., . . . Ahlström, H. (2017). Additional value of magnetic resonance-targeted biopsies to standard transrectal ultrasound-guided biopsies for detection of clinically significant prostate cancer. Scandinavian journal of urology, 51(2), 107-113
Open this publication in new window or tab >>Additional value of magnetic resonance-targeted biopsies to standard transrectal ultrasound-guided biopsies for detection of clinically significant prostate cancer
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2017 (English)In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 51, no 2, p. 107-113Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: The aim of this study was to evaluate the additional value of magnetic resonance imaging-targeted biopsy (MRI-TB) to standard transrectal ultrasound-guided biopsy (SB) for detection of clinically significant prostate cancer (PCa). An additional aim was to compare the biopsy results to MRI evaluation using a Likert scale.

MATERIALS AND METHODS: Patients with newly diagnosed localized PCa (n = 53) by clinical routine SB were prospectively included. The majority of the patients were scheduled for curative therapy before enrollment. The patients underwent multiparametric MRI (mpMRI) at 3 T using an endorectal coil followed by two MRI-TBs, using ultrasound with cognitive fusion. All included patients underwent MRI-TB, even those who had low to very low suspicion of significant PCa on mpMRI. The detection rate of significant cancer on SB versus SB + MRI-TB was compared in the 53 included patients and with whole-mounted histopathology as reference in 34 cases. Comparison of the biopsy results to MRI evaluation and interreader agreement calculation of five-point Likert score evaluation were performed.

RESULTS: In total, 32 significant (Gleason ≥7) PCa were detected by SB, while SB + MRI-TB detected an additional five significant PCa. MRI-TB alone detected 20 and missed 17 significant PCa. Ten of the significant PCa cases missed by MRI-TB had a Likert score of 3 or lower. Interreader agreement using the Likert scale was high, with a kappa value of 0.77 (95% confidence interval 0.63-0.92, p < 0.0001).

CONCLUSION: Detection of significant PCa increased by adding MRI-TB to SB. This may not be of enough clinical value to justify the use of targeted biopsies in this patient group.

Keywords
Magnetic resonance imaging, prostatic neoplasm, targeted biopsies, transrectal ultrasound-guided biopsy
National Category
Urology and Nephrology Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-325563 (URN)10.1080/21681805.2017.1281346 (DOI)000403629400003 ()28635568 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2017-06-26 Created: 2017-06-26 Last updated: 2017-10-19Bibliographically approved
Tammela, T. L., Häggman, M., Ladjevardi, S., Taari, K., Isotalo, T., Lennernäs, H., . . . Ahlström, H. (2017). An Intraprostatic Modified Release Formulation of Antiandrogen 2-Hydroxyflutamide for Localized Prostate Cancer. Journal of Urology, 198(6), 1333-1339
Open this publication in new window or tab >>An Intraprostatic Modified Release Formulation of Antiandrogen 2-Hydroxyflutamide for Localized Prostate Cancer
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2017 (English)In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 198, no 6, p. 1333-1339Article in journal (Refereed) Published
Abstract [en]

PURPOSE: To investigate tolerability, safety and antitumor effects of a novel intra-prostatic depot formulation of antiandrogen 2-hydroxyflutamide (2-HOF in NanoZolid(®)) in men with localized prostate cancer (PCa).

MATERIALS AND METHODS: Two clinical trials, LPC-002 and LPC-003, were conducted on a total of 47 men. The formulation was injected transrectally into the prostate with ultrasound guidance. In LPC-002 the effects on prostate specific antigen (PSA) and prostate volume (PV) were measured over 6 months on 24 patients. In LPC-003, antitumor effects were evaluated with histopathology, magnetic resonance imaging (MRI) including spectroscopy (MRS) during 6 or 8 weeks on 23 patients. In both studies, testosterone and 2-HOF in plasma were measured, as well as quality-of-life parameters.

RESULTS: In LPC-002 (mean dose 690 mg) a reduction in PSA and PV was observed. The nadir values for PSA and PV were on average 24.9 % and 14.0 % below baseline, respectively. When increasing the dose in LPC-003 (920 mg and 1740 mg), the average PSA dropped 16 % and 23 %, respectively, after 6 and 8 weeks. MRI/MRS showed morphological changes and a global drop in metabolite concentrations following treatment indicating an antitumor response. The injections did not result in hormone related side effects. In total, three serious adverse events were reported, all resolved by oral antibiotic treatment.

CONCLUSIONS: The intraprostatic injections of 2-HOF depot formulations indicated anti-tumor effects and proved safe and tolerable. However, for better anti-cancer effects higher doses and better dose distribution are suggested.

Keywords
NanoZolid, Prostate cancer, bioresorbable, calcium sulphate, local treatment, modified-release
National Category
Medical and Health Sciences Urology and Nephrology Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-327250 (URN)10.1016/j.juro.2017.07.072 (DOI)000417150900023 ()28736321 (PubMedID)
Available from: 2017-08-07 Created: 2017-08-07 Last updated: 2018-03-06Bibliographically approved
Regula, N. K., Lubberink, M., Jorulf, H., Ladjevardi, S., Häggman, M. & Sörensen, J. (2017). Dynamic Imaging of Prostate Cancer with 11C-acetate PET/CT. Paper presented at Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI), JUN 10-14, 2017, Denver, CO. Journal of Nuclear Medicine, 58(S1), Article ID 662.
Open this publication in new window or tab >>Dynamic Imaging of Prostate Cancer with 11C-acetate PET/CT
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2017 (English)In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 58, no S1, article id 662Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Objectives: Dynamic 11C-acetate PET/CT can be used to study tissue perfusion and carbon flux simultaneously, but studies in cancer are limited. We investigated the kinetics of 11C-acetate in prostate cancer subjects using parametric images with an image-derived input function (IDIF).

Methods: Twenty-one patients with newly diagnosed low-moderate risk prostate cancer were studied. All underwent pelvic MRI. Dynamic 11C-acetate (5 MBq/kg) PET/CT of the pelvis was acquired for 32 minutes with 32 time frames. An IDIF was acquired from iliac vessels with multiple small regions of interest (ROIs) and a standardized metabolite correction. Parametric images of K1 (extraction), k2 (oxidative metabolism) and Vd (=K1/k2, anabolic metabolism defined as carbon retention) were constructed using a one-tissue compartment model. ROIs of the largest cancer region in each patient and normal prostate tissue were drawn using information from MRI (T2 and DWI images) and from post-surgical histopathology of whole prostate sections (n=7).

Results: Mean PSA was 8.3±3.9. Median Gleason Sum was 6 (range 5-7). K1, Vd and SUVs were higher in cancerous regions compared to normal prostate for all patients (p<0.001). PSA correlated to early SUV (r=0.50, p=0.02) and K1 (r=0.48, p=0.03). Early and late SUVs were correlated to Vd (r>0.76, p<0.001) and K1 (r>0.61, p<0.005).

Conclusion: Parametric images could be used to visualize the 11C-acetate kinetics of the prostate. In this cohort of relatively low-risk cancers, PSA values were related to cancer perfusion. SUV of cancerous regions at any time point is primarily associated with anabolic metabolism. Research Support: Swedish Cancer Foundation (Cancerfonden)

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-333339 (URN)000404949903062 ()
Conference
Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI), JUN 10-14, 2017, Denver, CO
Funder
Swedish Cancer Society
Available from: 2017-11-14 Created: 2017-11-14 Last updated: 2017-11-14Bibliographically approved
Weis, J., von Below, C., Tolf, A., Ortiz-Nieto, F., Wassberg, C., Haggman, M., . . . Ahlström, H. (2017). Quantification of metabolite concentrations in benign and malignant prostate tissues using 3D proton MR spectroscopic imaging. Journal of Magnetic Resonance Imaging, 45(4), 1232-1240
Open this publication in new window or tab >>Quantification of metabolite concentrations in benign and malignant prostate tissues using 3D proton MR spectroscopic imaging
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2017 (English)In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 45, no 4, p. 1232-1240Article in journal (Refereed) Published
Abstract [en]

PURPOSE: To estimate concentrations of choline (Cho), spermine (Spm), and citrate (Cit) in prostate tissue using 3D proton magnetic resonance spectroscopic imaging (MRSI) with water as an internal concentration reference as well as to assess the relationships between the measured metabolites and also between the metabolites and apparent diffusion coefficient (ADC).

MATERIALS AND METHODS: Forty-six prostate cancer patients were scanned at 3T. Spectra were acquired with the point-resolved spectroscopy (PRESS) localization technique. Single-voxel spectra of four healthy volunteers were used to estimate T1 relaxation time of Spm. Spm, Cho concentrations, and ADC values of benign prostate tissues were correlated with Cit content.

RESULTS: The T1 value, 708 ± 132 msec, was estimated for Spm. Mean concentrations in the benign peripheral zone (PZ) were Cho, 4.5 ± 1 mM, Spm, 13.0 ± 4.4 mM, Cit, 64.4 ± 16.1 mM. Corresponding values in the benign central gland (CG) were Cho, 3.6 ± 1 mM, Spm, 13.3 ± 4.5 mM, Cit, 34.3 ± 12.9 mM. Concentrations of Cit and Spm were positively correlated in the benign PZ zone (r = 0.730) and CG (r = 0.664). Positive correlation was found between Cit and Cho in the benign CG (r = 0.705). Whereas Cit and ADC were positively correlated in the benign PZ (r = 0.673), only low correlation was found in CG (r = 0.265).

CONCLUSION: We have shown that it is possible to perform water-referenced quantitative 3D MRSI of the prostate at the cost of a relatively short prolongation of the acquisition time. The individual metabolite concentrations provide additional information compared to the previously used metabolite-to-citrate ratios.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-304633 (URN)10.1002/jmri.25443 (DOI)000397489100030 ()27556571 (PubMedID)
Available from: 2016-10-06 Created: 2017-05-30 Last updated: 2017-05-30Bibliographically approved
Ladjevardi, S., Weis, J., Sörensen, J., Tolf, A., Häggman, M., von Below, C. & Jorulf, H. (2014). A Comparison of Different Imaging Techniques for Localisation of Cancers in the Prostate. Open Prostate Cancer Journal, 7, 1-6
Open this publication in new window or tab >>A Comparison of Different Imaging Techniques for Localisation of Cancers in the Prostate
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2014 (English)In: Open Prostate Cancer Journal, ISSN 1876-8229, Vol. 7, p. 1-6Article in journal (Refereed) Published
Abstract [en]

The diagnostic accuracy of standard transrectal ultrasound-guided (TRUL) biopsy is limited due to the finite number of cores that can be obtained. It has been shown that the technique is not sufficiently reliable in defining the location and extent of prostatic cancer. The main aim of this study was to investigate the effectiveness of magnetic resonance imaging (MRI), and positron emission tomography (PET/CT) imaging techniques in pinpointing potential tumour lesions prior to prostate biopsy.

Material and methods

The study cohort consisted of 45 men with a raised prostate specific-antigen (PSA) level and/or suspected prostate cancer (PCa) at digital rectal examinations (DRE). Of the 45 patients, 23 had PCa detected with core needle biopsy (CNB). All had 11C acetate PET/CT imaging. Ten of those 23 patients underwent radical prostatectomy (RP), of those ten patients, eight patients had MR spectroscopic imaging (MRSI) with 3 T and six had diffusion weighted imaging (DWI) with apparent diffusion coefficient calculation (MRI DWI ADC). CNB, PET/CT, 2D MRSI and ADC map results were compared with postoperative specimen histopathology.

Results

The sensitivity of CNB, PET/CT, MRSI and DWI ADC were 0.53, 0.55, 0.79 and 0.95, whereas the specificity of was 0.88, 0.87, 0.46 and 0.73, respectively.

Conclusion

MRI improves the PCa detection by defining the areas of interest for targeted CNB of the prostate and can reduce the number of biopsies required

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-225428 (URN)10.2174/1876822901407010001 (DOI)
Available from: 2014-06-03 Created: 2014-06-03 Last updated: 2017-12-05Bibliographically approved
Ladjevardi, S., Auer, G., Castro, J., Ericsson, C., Zetterberg, A., Häggman, M., . . . Jorulf, H. (2014). Prostate biopsy sampling causes hematogenous dissemination of epithelial cellular material. Disease Markers, 707529
Open this publication in new window or tab >>Prostate biopsy sampling causes hematogenous dissemination of epithelial cellular material
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2014 (English)In: Disease Markers, ISSN 0278-0240, E-ISSN 1875-8630, p. 707529-Article in journal (Refereed) Published
Abstract [en]

The extent of epithelial cellular material (ECM) occurring in venous blood samples after diagnostic core needle biopsy (CNB) was studied in 23 patients with CNB diagnosed prostate cancer without provable metastases and 15 patients without cancer. The data show a significant increase of ECM in the peripheral blood sampled 20 seconds or 30 minutes after the last of 10 CNB procedures compared to the number of ECM detectable in the blood samples taken before the performance of CNB. The data indicate that diagnostic CNB of prostate cancer causes an extensive tissue trauma with a potential risk of cancer cell dissemination.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-216770 (URN)10.1155/2014/707529 (DOI)000330893600001 ()
Available from: 2014-01-24 Created: 2014-01-24 Last updated: 2017-12-06Bibliographically approved
Bill-Axelson, A., Holmberg, L., Garmo, H., Rider, J. R., Taari, K., Busch, C., . . . Johansson, J.-E. (2014). Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer. New England Journal of Medicine, 370(10), 932-942
Open this publication in new window or tab >>Radical Prostatectomy or Watchful Waiting in Early Prostate Cancer
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2014 (English)In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 370, no 10, p. 932-942Article in journal (Refereed) Published
Abstract [en]

BackgroundRadical prostatectomy reduces mortality among men with localized prostate cancer; however, important questions regarding long-term benefit remain. MethodsBetween 1989 and 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy and followed them through the end of 2012. The primary end points in the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) were death from any cause, death from prostate cancer, and the risk of metastases. Secondary end points included the initiation of androgen-deprivation therapy. ResultsDuring 23.2 years of follow-up, 200 of 347 men in the surgery group and 247 of the 348 men in the watchful-waiting group died. Of the deaths, 63 in the surgery group and 99 in the watchful-waiting group were due to prostate cancer; the relative risk was 0.56 (95% confidence interval [CI], 0.41 to 0.77; P=0.001), and the absolute difference was 11.0 percentage points (95% CI, 4.5 to 17.5). The number needed to treat to prevent one death was 8. One man died after surgery in the radical-prostatectomy group. Androgen-deprivation therapy was used in fewer patients who underwent prostatectomy (a difference of 25.0 percentage points; 95% CI, 17.7 to 32.3). The benefit of surgery with respect to death from prostate cancer was largest in men younger than 65 years of age (relative risk, 0.45) and in those with intermediate-risk prostate cancer (relative risk, 0.38). However, radical prostatectomy was associated with a reduced risk of metastases among older men (relative risk, 0.68; P=0.04). ConclusionsExtended follow-up confirmed a substantial reduction in mortality after radical prostatectomy; the number needed to treat to prevent one death continued to decrease when the treatment was modified according to age at diagnosis and tumor risk. A large proportion of long-term survivors in the watchful-waiting group have not required any palliative treatment. (Funded by the Swedish Cancer Society and others.) The randomized Swedish trial of prostatectomy versus watchful waiting in disease detected mainly clinically (not by PSA screening) continues to show a benefit for early prostatectomy. The number of men younger than 65 needed to treat to prevent one death is now four. The Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4), a randomized trial of radical prostatectomy versus watchful waiting in men with localized prostate cancer diagnosed before the era of prostate-specific antigen (PSA) testing, showed a survival benefit of radical prostatectomy as compared with observation at 15 years of follow-up.(1) By contrast, the Prostate Cancer Intervention versus Observation Trial (PIVOT), initiated in the early era of PSA testing, showed that radical prostatectomy did not significantly reduce prostate cancer-specific or overall mortality after 12 years.(2) PSA screening profoundly changes the clinical domain of study. Among other considerations, the substantial additional lead time ...

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-225105 (URN)10.1056/NEJMoa1311593 (DOI)000332309800010 ()
Available from: 2014-05-27 Created: 2014-05-27 Last updated: 2017-12-05Bibliographically approved
Armstrong, A. J., Häggman, M., Stadler, W. M., Gingrich, J. R., Assikis, V., Polikoff, J., . . . Pili, R. (2013). Long-term Survival and Biomarker Correlates of Tasquinimod Efficacy in a Multicenter Randomized Study of Men with Minimally Symptomatic Metastatic Castration-Resistant Prostate Cancer.. Clinical Cancer Research, 19(24), 6891-6901
Open this publication in new window or tab >>Long-term Survival and Biomarker Correlates of Tasquinimod Efficacy in a Multicenter Randomized Study of Men with Minimally Symptomatic Metastatic Castration-Resistant Prostate Cancer.
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2013 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 19, no 24, p. 6891-6901Article in journal (Refereed) Published
Abstract [en]

PURPOSE: Tasquinimod (Active Biotech) is an oral immunomodulatory, anti-angiogenic, and anti-metastatic agent that delayed metastatic disease progression in a randomized placebo-controlled phase II trial in men with metastatic castration-resistant prostate cancer (mCRPC). Here, we report long-term survival with biomarker correlates from this trial.

EXPERIMENTAL DESIGN: Two hundred and one (134 tasquinimod and 67 placebo) men with mCRPC were evaluated. Forty-one men randomized to placebo crossed over to tasquinimod. Survival data were collected with a median follow-up time of 37 months. Exploratory biomarker studies at baseline and over time were collected to evaluate potential mechanism-based correlates with tasquinimod efficacy including progression-free survival (PFS) and overall survival (OS).

RESULTS: With 111 mortality events, median OS was 33.4 months for tasquinimod versus 30.4 months for placebo overall, and 34.2 versus 27.1 months in men with bone metastases (n = 136), respectively. Multivariable analysis demonstrated an adjusted HR of 0.52 [95% confidence interval (CI), 0.35-0.78; P = 0.001] for PFS and 0.64 (95% CI, 0.42-0.97; P = 0.034) for OS, favoring tasquinimod. Time-to-symptomatic progression was improved with tasquinimod (P = 0.039, HR = 0.42). Toxicities tended to be mild in nature and improved over time. Biomarker analyses suggested a favorable impact on bone alkaline phosphatase and lactate dehydrogenase (LDH) over time and a transient induction of inflammatory biomarkers, VEGF-A, and thrombospondin-1 levels with tasquinimod. Baseline levels of thrombospondin-1 less than the median were predictive of treatment benefit.

CONCLUSIONS: The survival observed in this trial of men with minimally symptomatic mCRPC suggests that the prolongation in PFS with tasquinimod may lead to a survival advantage in this setting, particularly among men with skeletal metastases, and has a favorable risk:benefit ratio. 

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-216769 (URN)10.1158/1078-0432.CCR-13-1581 (DOI)000328938700026 ()24255071 (PubMedID)
Available from: 2014-01-24 Created: 2014-01-24 Last updated: 2017-12-06Bibliographically approved
Carducci, M., Armstrong, A., Haggman, M., Stadler, W. M., Gingrich, J. R., Assikis, V., . . . Pili, R. (2012). Tasquinimod mechanism of action biomarkers: correlation with pfs and survival in men with metastatic castrate resistant prostate cancer treated in a randomized phase 2 trial. Paper presented at 37th Congress of the European-Society-for-Medical-Oncology (ESMO), SEP 28-OCT 02, 2012, Vienna, AUSTRIA. Annals of Oncology, 23(S9), 303-303
Open this publication in new window or tab >>Tasquinimod mechanism of action biomarkers: correlation with pfs and survival in men with metastatic castrate resistant prostate cancer treated in a randomized phase 2 trial
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2012 (English)In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 23, no S9, p. 303-303Article in journal, Meeting abstract (Other academic) Published
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-185373 (URN)000309409001400 ()
Conference
37th Congress of the European-Society-for-Medical-Oncology (ESMO), SEP 28-OCT 02, 2012, Vienna, AUSTRIA
Available from: 2012-11-26 Created: 2012-11-22 Last updated: 2017-12-07Bibliographically approved
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