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Lindman, Henrik
Publications (10 of 48) Show all publications
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
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
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
Wickberg, A., Liljegren, G., Killander, F., Lindman, H., Bjohle, J., Carlberg, M., . . . Villman, K. (2018). Omitting radiotherapy in women >= 65 years with low-risk early breast cancer after breast-conserving surgery and adjuvant endocrine therapy is safe. European Journal of Surgical Oncology, 44(7), 951-956
Open this publication in new window or tab >>Omitting radiotherapy in women >= 65 years with low-risk early breast cancer after breast-conserving surgery and adjuvant endocrine therapy is safe
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2018 (English)In: European Journal of Surgical Oncology, ISSN 0748-7983, E-ISSN 1532-2157, Vol. 44, no 7, p. 951-956Article in journal (Refereed) Published
Abstract [en]

Purpose: The aim of this study was to verify if radiotherapy (RT) safely can be omitted in older women treated for estrogen-receptor positive early breast cancer with breast-conserving surgery (BCS) and endocrine therapy (ET). Patients and Methods: Eligibility criteria were: consecutive patients with age >= 65 years, BCS + sentinel node biopsy, clear margins, unifocal T1N0M0 breast cancer tumor, Elston-Ellis histological grade 1 or 2 and estrogen receptor-positive tumor. After informed consent, adjuvant ET for 5 years was prescribed. Primary endpoint was ipsilateral breast tumor recurrence (IBTR). Secondary endpoints were contralateral breast cancer and overall survival. Results: Between 2006 and 2012, 603 women were included from 14 Swedish centers. Median age was 71.1 years (range 65-90). After a median follow-up of 68 months 16 IBTR (cumulative incidence at five-year follow-up; 1.2%, 95% CI, 0.6% to 2.5%), 6 regional recurrences (one combined with IBTR), 2 distant recurrences (both without IBTR or regional recurrence) and 13 contralateral breast cancers were observed. There were 48 deaths. One death (2.1%) was due to breast cancer and 13 (27.1%) were due to other cancers (2 endometrial cancers). Five-year overall survival was 93.0% (95% CI, 90.5% to 94.9%). Conclusion: BCS and ET without RT seem to be a safe treatment option in women >= 65 years with early breast cancer and favorable histopathology. The risk of IBTR is comparable to the risk of contralateral breast cancer. Moreover, concurrent morbidity dominates over breast cancer as leading cause of death in this cohort with low-risk breast tumors.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2018
Keywords
Breast-conserving surgery, Endocrine therapy, Postoperative radiotherapy
National Category
Cancer and Oncology Surgery
Identifiers
urn:nbn:se:uu:diva-361106 (URN)10.1016/j.ejso.2018.04.002 (DOI)000437391100005 ()29709338 (PubMedID)
Available from: 2018-09-21 Created: 2018-09-21 Last updated: 2018-09-21Bibliographically approved
Joensuu, H. & Lindman, H. (2018). Taxane Followed by Anthracycline or Vice Versa: Impact of Sequential Order on Breast Cancer Recurrence? Reply [Letter to the editor]. JAMA Oncology, 4(3), 423-424
Open this publication in new window or tab >>Taxane Followed by Anthracycline or Vice Versa: Impact of Sequential Order on Breast Cancer Recurrence? Reply
2018 (English)In: JAMA Oncology, ISSN 2374-2437, E-ISSN 2374-2445, Vol. 4, no 3, p. 423-424Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
AMER MEDICAL ASSOC, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-356896 (URN)10.1001/jamaoncol.2017.3352 (DOI)000426995100036 ()29075758 (PubMedID)
Available from: 2018-08-09 Created: 2018-08-09 Last updated: 2018-08-09Bibliographically approved
Netterberg, I., Karlsson, M. O., Nielsen, E. I., Quartino, A. L., Lindman, H. & Friberg, L. E. (2018). The risk of febrile neutropenia in breast cancer patients following adjuvant chemotherapy is predicted by the time course of interleukin-6 and C-reactive protein by modelling.. British Journal of Clinical Pharmacology, 84(3), 490-500
Open this publication in new window or tab >>The risk of febrile neutropenia in breast cancer patients following adjuvant chemotherapy is predicted by the time course of interleukin-6 and C-reactive protein by modelling.
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2018 (English)In: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 84, no 3, p. 490-500Article in journal (Refereed) Published
Abstract [en]

AIMS: Early identification of patients with febrile neutropenia (FN) is desirable for initiation of preventive treatment, such as with antibiotics. In this study, the time courses of two inflammation biomarkers, interleukin (IL)-6 and C-reactive protein (CRP), following adjuvant chemotherapy of breast cancer, were characterized. The potential to predict development of FN by IL-6 and CRP, and other model-derived and clinical variables, was explored.

METHODS: The IL-6 and CRP time courses in cycles 1 and 4 of breast cancer treatment were described by turnover models where the probability for an elevated production following initiation of chemotherapy was estimated. Parametric time-to-event models were developed to describe FN occurrence to assess: (i) predictors available before chemotherapy is initiated; (ii) predictors available before FN occurs; and (iii) predictors available when FN occurs.

RESULTS: The IL-6 and CRP time courses were successfully characterized with peak IL-6 typically occurring 2 days prior to CRP peak. Of all evaluated variables the CRP time course was most closely associated with the occurrence of FN. Since the CRP peak typically occurred at the time of FN diagnosis it will, however, have limited value for identifying the need for preventive treatment. The time course of IL-6 was the predictor that could best forecast FN events. Of the variables available at baseline, age was the best, although in comparison a relatively weak, predictor.

CONCLUSIONS: The developed models add quantitative knowledge about IL-6 and CRP and their relationship to the development of FN. The study suggests that IL-6 may have potential as a clinical predictor of FN if monitored during myelosuppressive chemotherapy.

Keywords
C-reactive protein, NONMEM, adjuvant chemotherapy, febrile neutropenia, interleukin-6
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-343812 (URN)10.1111/bcp.13477 (DOI)000424877400009 ()29178353 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2018-03-01 Created: 2018-03-01 Last updated: 2018-04-09Bibliographically approved
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
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