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Lindman, Henrik
Publications (10 of 52) Show all publications
Velikyan, I., Schweighoefer, P., Feldwisch, J., Seemann, J., Frejd, F. Y., Lindman, H. & Sörensen, J. (2019). Diagnostic HER2-binding radiopharmaceutical, [Ga-68]Ga-ABY-025, for routine clinical use in breast cancer patients. American Journal of Nuclear Medicine and Molecular Imaging, 9(1), 12-23
Open this publication in new window or tab >>Diagnostic HER2-binding radiopharmaceutical, [Ga-68]Ga-ABY-025, for routine clinical use in breast cancer patients
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2019 (English)In: American Journal of Nuclear Medicine and Molecular Imaging, ISSN 2160-8407, Vol. 9, no 1, p. 12-23Article in journal (Refereed) Published
Abstract [en]

[Ga-68]Ga-ABY-025/PET-CT targeting human epidermal growth factor receptor type 2 (HER2) has demonstrated its potential clinical value for the detection and quantification of HER2 in a phase I clinical study with breast cancer patients. Previously, the radiopharmaceutical was prepared manually, however larger scale of multicenter clinical trials and routine healthcare requires automation of the production process to limit the operator radiation dose, improve tracer manufacturing robustness, and provide on-line documentation for good manufacturing practice (GMP) compliance. The production of [Ga-68]Ga-ABY-025 was implemented on the Modular-Lab PharmTrace synthesis platform (Eckert & Ziegler) and disposable cassettes were developed. Pharmaceutical grade Ge-68/Ga-68 generator (GalliaPharm (R)) was used in the study. The active pharmaceutical ingredient starting material ABY-025 (GMP grade) was provided by Affibody AB. The patient examinations were conducted using a Discovery MI PET/CT scanner (20 cm FOV, GE Healthcare). Reproducible and GMP compliant fully automated production of [Ga-68]Ga-ABY-025 was developed. The radiochemical purity of the product was 98.7 +/- 0.6% with total peptide content of 315 +/- 15 mu g (n = 3). Radionuclidic purity, sterility, endotoxin content, residual solvent content, and sterile filter integrity were controlled and met acceptance criteria. The product was stable at ambient temperature for at least 2 h. The primary tumor and metastasis were detected with SUVmax values of 8.3 and 16.0, respectively. Automated production of [Ga-68]Ga-ABY-025 was established and the process was validated enabling standardized multicenter phase II and III clinical trials and routine clinical use. Patient examinations conformed to the radiopharmaceutical biodistribution observed in the previous phase I study.

Place, publisher, year, edition, pages
E-CENTURY PUBLISHING CORP, 2019
Keywords
Affibody, breast cancer, clinical study, HER2, GMP, gallium-68
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-379777 (URN)000460442600002 ()
Funder
Swedish Cancer SocietyThe Breast Cancer Foundation
Available from: 2019-03-21 Created: 2019-03-21 Last updated: 2019-03-21Bibliographically approved
Cazzaniga, M. E., Ciruelos, E., Fabi, A., Garcia-Saenz, J., Lindman, H., Mavroudis, D., . . . Torri, V. (2019). Metastatic or locally advanced breast cancer patients: towards an expert consensus on nab-paclitaxel treatment in HER2-negative tumoursthe MACBETH project. Cancer Chemotherapy and Pharmacology, 83(2), 301-318
Open this publication in new window or tab >>Metastatic or locally advanced breast cancer patients: towards an expert consensus on nab-paclitaxel treatment in HER2-negative tumoursthe MACBETH project
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2019 (English)In: Cancer Chemotherapy and Pharmacology, ISSN 0344-5704, E-ISSN 1432-0843, Vol. 83, no 2, p. 301-318Article in journal (Refereed) Published
Abstract [en]

Introduction: Despite the large use of nab-paclitaxel as a treatment option in metastatic breast cancer (MBC) across different countries, no definitive data are available in particular clinical situations.

Areas covered: Efficacy, safety and schedule issues concerning available literature on nab-paclitaxel in advanced breast cancer and in specific subgroups of patients have been discussed and voted during an International Expert Meeting. Ten expert specialists in oncology, with extensive clinical experience on Nab-P and publications in the field of MBC have been identified. Six scientific areas of interest have been covered, generating 13 specific Statements for Nab-P, after literature review. For efficacy issues, a summary of research quality was performed adopting the GRADE algorithm for evidence scoring. The panel members were invited to express their opinion on the statements, in case of disagreement all the controversial opinions and the relative motivations have been made public.

Expert opinion: Consensus was reached in 30.8% of the Nab-P statements, mainly those regarding safety issues, whereas ones regarding efficacy and schedule still remain controversial areas, requiring further data originated by the literature.

Keywords
Expert meeting, Nab-paclitaxel, Breast cancer, Weekly schedule, Neuropathy
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-378731 (URN)10.1007/s00280-018-3717-2 (DOI)000459155300007 ()30460489 (PubMedID)
Available from: 2019-03-08 Created: 2019-03-08 Last updated: 2019-03-08Bibliographically approved
Lindman, H., Andersson, M., Ahlgren, J., Balslev, E., Sverrisdottir, A., Holmberg, S. B., . . . Blomqvist, C. (2018). A randomised study of tailored toxicity-based dosage of fluorouracil-epirubicin-cyclophosphamide chemotherapy for early breast cancer (SBG 2000-1). European Journal of Cancer, 94, 79-86
Open this publication in new window or tab >>A randomised study of tailored toxicity-based dosage of fluorouracil-epirubicin-cyclophosphamide chemotherapy for early breast cancer (SBG 2000-1)
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2018 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 94, p. 79-86Article in journal (Refereed) Published
Abstract [en]

Study aim: Retrospective studies have demonstrated a worse outcome in breast cancer patients not developing leukopenia during adjuvant chemotherapy. The SBG 2000-1 is the first randomised trial designed to compare individually dosed chemotherapy without G-CSF support based on grade of toxicity to standard-dosed chemotherapy based on body surface area (BSA). Methods: Patients with early breast cancer were included and received the first cycle of standard FEC (fluorouracil 600 mg/m(2), epirubicin 60 mg/m(2), cyclophosphamide 600 mg/m2). Patients with nadir leukopenia grade 0-2 after first cycle were randomised between either 6 additional courses of tailored FEC with increased doses (E 75-90 mg/m(2), C 900-1200 mg/m(2)) or fixed treatment with 6 standard FEC. Patients with grade 3-4 leukopenia were registered and treated with 6 standard FEC. Primary end-point was distant disease-free survival (DDFS). Results: The study enrolled 1535 patients, of which 1052 patients were randomised to tailored FEC (N = 524) or standard FEC (N = 528), whereas 401 patients with leukopenia grade 3-4 continued standard FEC and formed the registered cohort. Dose escalation did not statistically significantly improve 10-year DDFS (79% and 77%, HR 0.87, CI 0.67-1.14, P = 0.32) or OS (82% and 78%, respectively, HR 0.89, CI 0.57e1.16, P = 0.38). Corresponding estimates for the registered group of patients were DDFS 79% and OS 82%, respectively. Conclusions: The SBG 2000-1 study failed to show a statistically significant improvement of escalated and tailored-dosed chemotherapy compared with standard BSA-based chemotherapy in patients with low haematological toxicity, although all efficacy parameters showed a numerical advantage for tailored treatment.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2018
Keywords
Adjuvant, Breast cancer, Chemotherapy, Dosage, Dose tailoring, Leukopenia
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-352580 (URN)10.1016/j.ejca.2018.02.016 (DOI)000429403700009 ()29547834 (PubMedID)
Available from: 2018-08-07 Created: 2018-08-07 Last updated: 2018-08-07Bibliographically approved
Joensuu, H., Fraser, J., Wildiers, H., Huovinen, R., Auvinen, P., Utriainen, M., . . . Lindman, H. (2018). Abstract GS3-04: A randomized phase III study of adjuvant trastuzumab for a duration of 9 weeks versus 1 year, combined with adjuvant taxane-anthracycline chemotherapy, for early HER2-positive breast cancer (the SOLD study). 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 GS3-04: A randomized phase III study of adjuvant trastuzumab for a duration of 9 weeks versus 1 year, combined with adjuvant taxane-anthracycline chemotherapy, for early HER2-positive breast cancer (the SOLD study)
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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-351601 (URN)10.1158/1538-7445.SABCS17-GS3-04 (DOI)000425489400018 ()
Conference
San Antonio Breast Cancer Symposium, DEC 05-09, 2017, San Antonio, TX
Note

Supplement: S, Meeting Abstract: GS3-04.

Wos title: A randomized phase III study of adjuvant trastuzumab for a duration of 9 weeks versus 1 year, combined with adjuvant taxane-anthracycline chemotherapy, for early HER2-positive breast cancer (the SOLD study)

Available from: 2018-05-29 Created: 2018-05-29 Last updated: 2018-05-29Bibliographically approved
Joensuu, H., Fraser, J., Wildiers, H., Huovinen, R., Auvinen, P., Utriainen, M., . . . Lindman, H. (2018). Effect of Adjuvant Trastuzumab for a Duration of 9 Weeks vs 1 Year With Concomitant Chemotherapy for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer The SOLD Randomized Clinical Trial. JAMA Oncology, 4(9), 1199-1206
Open this publication in new window or tab >>Effect of Adjuvant Trastuzumab for a Duration of 9 Weeks vs 1 Year With Concomitant Chemotherapy for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer The SOLD Randomized Clinical Trial
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2018 (English)In: JAMA Oncology, ISSN 2374-2437, E-ISSN 2374-2445, Vol. 4, no 9, p. 1199-1206Article in journal (Refereed) Published
Abstract [en]

Importance: Trastuzumab plus chemotherapy is the standard adjuvant treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. While the standard duration of trastuzumab treatment is 12 months, the benefits and harms of trastuzumab continued beyond the chemotherapy are unclear.

Objective: To evaluate the efficacy and safety of adjuvant trastuzumab continued beyond chemotherapy in women treated with up-front chemotherapy containing a taxane and trastuzumab.

Design, Setting, and Participants: Open-label, randomized (1:1) clinical trial including women with HER2-positive breast cancer. Chemotherapy was identical in the 2 groups, consisting of 3 cycles of 3-weekly docetaxel (either 80 or 100 mg/m2) plus trastuzumab for 9 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide. Thereafter, no trastuzumab was administered in the 9-week group, whereas controls received trastuzumab to complete 1 year of administration. Disease-free survival (DFS) was compared between the groups using a Cox model and the noninferiority approach. The estimated sample size was 2168 patients (1-sided testing, with a relative noninferiority margin of 1.3). From January 3, 2008, to December 16, 2014, 2176 patients were accrued from 7 countries.

Intervention: Docetaxel plus trastuzumab for 9 weeks, followed by 3 cycles of fluorouracil, epirubicin, and cyclophosphamide in both groups. Controls continued trastuzumab to 1 year.

Main Outcomes and Measures: The primary objective was DFS; secondary objectives included distant disease–free survival, overall survival, cardiac DFS, and safety.

Results: In the 2174 women analyzed, median age was 56 (interquartile range [IQR], 48-64) years. The median follow-up was 5.2 (IQR, 3.8-6.7) years. Noninferiority of the 9-week treatment could not be demonstrated for DFS (hazard ratio, 1.39; 2-sided 90% CI, 1.12-1.72). Distant disease–free survival and overall survival did not differ substantially between the groups. Thirty-six (3%) and 21 (2%) patients in the 1-year and the 9-week groups, respectively, had cardiac failure; the left ventricle ejection fraction was better maintained in the 9-week group. An interaction was detected between the docetaxel dose and DFS; patients in the 9-week group treated with 80 mg/m2 had inferior and those treated with 100 mg/m2 had similar DFS as patients in the 1-year group.

Conclusions and Relevance: Nine weeks of trastuzumab was not noninferior to 1 year of trastuzumab when given with similar chemotherapy. Cardiac safety was better in the 9-week group. The docetaxel dosing with trastuzumab requires further study.

Trial Registration: ClinicalTrials.gov Identifier: NCT00593697

Place, publisher, year, edition, pages
AMER MEDICAL ASSOC, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-366270 (URN)10.1001/jamaoncol.2018.1380 (DOI)000444765300012 ()29852043 (PubMedID)
Funder
Academy of Finland
Available from: 2018-11-26 Created: 2018-11-26 Last updated: 2018-11-26Bibliographically approved
Lindman, H., Haji, A., Jernling, M. & Schiza, A. (2018). Evidence on the occurrence of brain metastases amongst deceased metastatic breast cancer patients from an Uppsala county disease registry. Paper presented at 11th European Breast Cancer Conference (EBCC), MAR 21-23, 2018, Barcelona, SPAIN. European Journal of Cancer, 92, S118-S118
Open this publication in new window or tab >>Evidence on the occurrence of brain metastases amongst deceased metastatic breast cancer patients from an Uppsala county disease registry
2018 (English)In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 92, p. S118-S118Article 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-357178 (URN)000429103100318 ()
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
Lundgren, C., Lindman, H., Rolander, B. & Ekholm, M. (2018). Good adherence to adjuvant endocrine therapy in early breast cancer: a population-based study based on the Swedish prescribed Drug Register. Acta Oncologica, 57(7), 935-940
Open this publication in new window or tab >>Good adherence to adjuvant endocrine therapy in early breast cancer: a population-based study based on the Swedish prescribed Drug Register
2018 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 57, no 7, p. 935-940Article in journal (Refereed) Published
Abstract [en]

Introduction: Adjuvant endocrine therapy improves recurrence-free and overall survival in primary breast cancer. However, not all patients complete their planned treatment, mostly because of side-effects. The aim of this study was to examine the adherence to adjuvant endocrine therapy in a cohort of primary breast cancer patients in Region Jonkoping County, Sweden, after 3 and 5 years.

Material and methods: The Swedish Breast Cancer Register was used to identify patients diagnosed with hormone receptor positive breast cancer in Region Jonkoping County between 2009 and 2012. Adherence was evaluated based on data from the Swedish Prescribed Drug Register, and Medication Possession Ratio (MPR), defined as the days' supply of medication during the period from the first dispensing till the last dispensing in the time period (3 and 5 years), divided by number of days. Adherence was defined as MPR >= 80%. Regression analyses were used to identify subgroups associated with adherence; age, type of endocrine treatment, additional adjuvant therapy, and hospital responsible for the follow-up (Eksjo, Jonkoping, and Varnamo).

Results: We identified 634 patients who were recommended adjuvant endocrine therapy and to be able to estimate adherence after 3 and 5 years, 488 patients were included in the analysis. After 3 years of treatment, 91.2% of the patients (95% confidence interval (0) 88.7-93.6; n = 445), were found to be adherent. The corresponding figure for the 271 patients who had completed 5 years of treatment was 91.5% (95% CI 88.2-94.8; n=248). No subgroups (age, endocrine therapy, radio/chemotherapy, or hospital) were significantly associated with adherence in the multiple logistic regression analysis.

Discussion: This study shows substantially higher adherence to adjuvant endocrine therapy than previously reported. Reasons for this could be differences in routines for therapy information and follow-up, but this needs to be further investigated.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2018
National Category
Cancer and Oncology Nursing
Identifiers
urn:nbn:se:uu:diva-362853 (URN)10.1080/0284186X.2018.1442932 (DOI)000441790600008 ()29493327 (PubMedID)
Funder
Futurum - Academy for Health and Care, Jönköping County Council, Sweden
Available from: 2018-10-15 Created: 2018-10-15 Last updated: 2018-10-15Bibliographically approved
Alhuseinalkhudhur, A., Lubberink, M., Velikyan, I., Tolmachev, V., Frejd, F., Feldwisch, J., . . . Sörensen, J. (2018). Kinetic Analysis of the HER2-binding ABY-025 Affibody Using Dynamic PET in Patients with Metastatic Breast Cancer. Paper presented at 31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY. European Journal of Nuclear Medicine and Molecular Imaging, 45, S457-S457
Open this publication in new window or tab >>Kinetic Analysis of the HER2-binding ABY-025 Affibody Using Dynamic PET in Patients with Metastatic Breast Cancer
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2018 (English)In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 45, p. S457-S457Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
Springer, 2018
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-372956 (URN)000449266204116 ()
Conference
31st Annual Congress of the European-Association-of-Nuclear-Medicine (EANM), OCT 13-17, 2018, Dusseldorf, GERMANY
Available from: 2019-01-24 Created: 2019-01-24 Last updated: 2019-01-24Bibliographically approved
Matikas, A., Margolin, S., Hellström, M., Johansson, H., Bengtsson, N.-O., Karlsson, L., . . . Bergh, J. (2018). Long-term safety and survival outcomes from the Scandinavian Breast Group 2004-1 randomized phase II trial of tailored dose-dense adjuvant chemotherapy for early breast cancer. Breast Cancer Research and Treatment, 168(2), 349-355
Open this publication in new window or tab >>Long-term safety and survival outcomes from the Scandinavian Breast Group 2004-1 randomized phase II trial of tailored dose-dense adjuvant chemotherapy for early breast cancer
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2018 (English)In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 168, no 2, p. 349-355Article in journal (Refereed) Published
Abstract [en]

Although adjuvant polychemotherapy improves outcomes for early breast cancer, the significant variability in terms of pharmacokinetics results in differences in efficacy and both short and long-term toxicities. Retrospective studies support the use of dose tailoring according to the hematologic nadirs. The SBG 2004-1 trial was a randomized feasibility phase II study which assessed tailored dose-dense epirubicin and cyclophosphamide (EC) followed by docetaxel (T) (group A), the same regimen with fixed doses (group B) and the TAC regimen (group C). Women aged 18-65 years, ECOG PS 0-1 with at least one positive axillary lymph node were randomized 1:1:1. The primary endpoint of the study was the safety and feasibility of the treatment. Toxicity was graded according to CTC-AE version 3.0. The design and short-term toxicity have been previously published. Here, we report safety and efficacy data after 10 years of follow-up. A total of 124 patients were included in the study. After a median follow-up of 10.3 years, the probability for 10-year survival was 78.5, 75.1, and 63.4% and for relapse free survival 64.1, 71.0, and 59.5% for groups A, B, and C, respectively. There were no cases of clinically diagnosed cardiotoxicity or hematologic malignancies. No patient was lost to follow-up. In this randomized phase II trial, tailored dose adjuvant chemotherapy was feasible, without an increased risk for long-term adverse events after a median follow-up of 10 years.

Place, publisher, year, edition, pages
SPRINGER, 2018
Keywords
Adjuvant chemotherapy, Breast cancer, Dose-dense, Randomized, Tailored dose
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-350272 (URN)10.1007/s10549-017-4599-4 (DOI)000426778200006 ()29190004 (PubMedID)
Funder
Swedish Cancer SocietyKing Gustaf V Jubilee FundThe Karolinska Institutet's Research FoundationSwedish Research CouncilStockholm County Council
Available from: 2018-05-14 Created: 2018-05-14 Last updated: 2018-05-14Bibliographically approved
Ryden, L., Loman, N., Larsson, C., Hegardt, C., Vallon-Christersson, J., Malmberg, M., . . . Borg, Å. (2018). Minimizing inequality in access to precision medicine in breast cancer by real-time population-based molecular analysis in the SCAN-B initiative. British Journal of Surgery, 105(2), E158-E168
Open this publication in new window or tab >>Minimizing inequality in access to precision medicine in breast cancer by real-time population-based molecular analysis in the SCAN-B initiative
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2018 (English)In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 105, no 2, p. E158-E168Article in journal (Refereed) Published
Abstract [en]

Background: Selection of systemic therapy for primary breast cancer is currently based on clinical biomarkers along with stage. Novel genomic tests are continuously being introduced as more precise tools for guidance of therapy, although they are often developed for specific patient subgroups. The Sweden Cancerome Analysis Network - Breast (SCAN-B) initiative aims to include all patients with breast cancer for tumour genomic analysis, and to deliver molecular subtype and mutational data back to the treating physician.

Methods: An infrastructure for collection of blood and fresh tumour tissue from all patients newly diagnosed with breast cancer was set up in 2010, initially including seven hospitals within the southern Sweden regional catchment area, which has 1.8 million inhabitants. Inclusion of patients was implemented into routine clinical care, with collection of tumour tissue at local pathology departments for transport to the central laboratory, where routines for rapid sample processing, RNA sequencing and biomarker reporting were developed.

Results: More than 10 000 patients from nine hospitals have currently consented to inclusion in SCAN-B with high (90 per cent) inclusion rates from both university and secondary hospitals. Tumour samples and successful RNA sequencing arc being obtained from more than 70 per cent of patients, showing excellent representation compared with the national quality registry as a truly population-based cohort. Molecular biomarker reports can be delivered to multidisciplinary conferences within 1 week.

Conclusion: Population-based collection of fresh tumour tissue is feasible given a decisive joint effort between academia and collaborative healthcare groups, and with governmental support. An infrastructure for genomic analysis and prompt data output paves the way for novel systemic therapy for patients from all hospitals, irrespective of size anti location.

Place, publisher, year, edition, pages
WILEY, 2018
National Category
Surgery Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-351772 (URN)10.1002/bjs.10741 (DOI)000429002100016 ()29341157 (PubMedID)
Funder
Swedish Cancer Society, CAN 2016/659VINNOVA, 2014-00484
Available from: 2018-06-04 Created: 2018-06-04 Last updated: 2018-06-04Bibliographically approved
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