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Article ; Online: Pazopanib for patients with advanced soft tissue sarcomas in a real-life setting.

Sleijfer, Stefan

2016 Volume 122, Issue 9, Page(s) 1346–1348

MeSH term(s)	Humans ; Pyrimidines/therapeutic use ; Sarcoma/drug therapy ; Soft Tissue Neoplasms/drug therapy ; Sulfonamides/therapeutic use
Chemical Substances	Pyrimidines ; Sulfonamides
Language	English
Publishing date	2016--01
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.29963
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Article ; Online: "It's the economy, stupid": strategies for improved cost containment in cancer treatment.

Sleijfer, S

Clinical pharmacology and therapeutics

2014 Volume 95, Issue 4, Page(s) 365–367

Abstract: The advent of numerous novel antitumor compounds has improved the prognosis of many cancer patients but has also substantially increased the costs of cancer care and put more pressure on health-care budgets. This situation increasingly raises questions ... ...

Abstract	The advent of numerous novel antitumor compounds has improved the prognosis of many cancer patients but has also substantially increased the costs of cancer care and put more pressure on health-care budgets. This situation increasingly raises questions such as the extent to which these drugs offer value sufficient to justify their cost and how to accommodate the increasing costs of cancer care. Here I look at the various aspects that affect cancer care economics and offer potential solutions.
MeSH term(s)	Antineoplastic Agents/economics ; Antineoplastic Agents/therapeutic use ; Budgets ; Cost Control ; Drug Costs ; Drug Design ; Health Care Costs ; Humans ; Neoplasms/drug therapy ; Neoplasms/economics ; Neoplasms/pathology ; Prognosis
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2014-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	123793-7
ISSN	1532-6535 ; 0009-9236
ISSN (online)	1532-6535
ISSN	0009-9236
DOI	10.1038/clpt.2014.9
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Zs.A 20: Show issues

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Article ; Online: Bridging the Translational Divide in Oncology:

Sleijfer, Stefan / Lolkema, Martijn

Clinical cancer research : an official journal of the American Association for Cancer Research

2020 Volume 26, Issue 15, Page(s) 3897–3898

Abstract: A study was presented in which sarcomas were microinjected simultaneously with several drugs to study the pharmacodynamic response after resection. This platform may represent a future way of probing efficacy of anticancer agents in the relevant model ... ...

Abstract	A study was presented in which sarcomas were microinjected simultaneously with several drugs to study the pharmacodynamic response after resection. This platform may represent a future way of probing efficacy of anticancer agents in the relevant model system: human tumors.
MeSH term(s)	Antineoplastic Agents ; Humans ; Sarcoma ; Soft Tissue Neoplasms ; Tumor Microenvironment
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2020-06-01
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-20-1452
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Zs.A 4223: Show issues

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Article ; Online: Apolipoprotein B mRNA-Editing Catalytic Polypeptide-Like-Induced Protein Changes in Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Throughout Disease Progression.

Bos, Manouk K / Smid, Marcel / Sleijfer, Stefan / Martens, John W M

JCO precision oncology

2022 Volume 6, Page(s) e2100190

Abstract: ... whereas termination codons (Glutamine[Q]>STOP[X] and Serine[S]>STOP[X]) occurred in tumor suppressor genes and, mostly, not ...

Abstract	Purpose: Apolipoprotein B mRNA-Editing Catalytic Polypeptide-like (APOBEC) enzymes are mutagenic factors contributing to tumor progression and therapy resistance. However, the effects of APOBEC-induced protein changes have not been systematically assessed. Here, we describe the effects of APOBEC on the coding sequence in primary and metastatic estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC). Methods: We determined the enrichment of amino acid (AA) changes resulting from APOBEC mutagenesis in 323 primary BC tumors and 424 metastatic breast cancer (mBC) lesions via comparison with a simulated mutational genomic landscape not under selection pressure. We subsequently explored genes with recurrent APOBEC-associated AA changes and investigated the clonality of individual APOBEC-associated mutations. Using public sequencing data from an independent primary BC and mBC cohort, we further confirm our findings by reporting genes having these enriched AA changes in an APOBEC context. Results: Our analysis demonstrated that several APOBEC-derived AA changes are significantly enriched compared with a simulated AA change distribution drawn at random. Among the enriched AA changes, Glutamate(E)>Lysine(K) and Glutamate(E)>Glutamine(Q) were mostly found at hotspots in oncogenes, whereas termination codons (Glutamine[Q]>STOP[X] and Serine[S]>STOP[X]) occurred in tumor suppressor genes and, mostly, not at hotspot locations. These mutations are found in genes contributing to BC initiation, eg, introduction of termination codons in Conclusion: Our results show that APOBEC mutagenesis recurrently targets various known drivers of BC initiation, progression, and endocrine resistance.
MeSH term(s)	APOBEC Deaminases/genetics ; Breast Neoplasms/chemistry ; Breast Neoplasms/genetics ; Disease Progression ; Female ; Humans ; Receptor, ErbB-2/analysis ; Receptors, Estrogen/analysis
Chemical Substances	Receptors, Estrogen ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1) ; APOBEC Deaminases (EC 3.5.4.5)
Language	English
Publishing date	2022-01-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2473-4284
ISSN (online)	2473-4284
DOI	10.1200/PO.21.00190
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Article: Combatting the rising costs of cancer drugs; interventions from a university hospital's perspective.

Dane, Aniek / van Leeuwen, Roelof / Hoedemakers, Maaike / van der Kuy, Hugo / Sleijfer, Stefan

Frontiers in pharmacology

2023 Volume 14, Page(s) 1264951

Abstract: Rapid increase in cost continues to have negative impact on patients' accessibility to life-changing anticancer medications. Moreover, the rising cost does not equate to similar increase in medication effectiveness. We recognise our responsibility as a ... ...

Abstract	Rapid increase in cost continues to have negative impact on patients' accessibility to life-changing anticancer medications. Moreover, the rising cost does not equate to similar increase in medication effectiveness. We recognise our responsibility as a university hospital to tackle this imbalance and strive to provide high quality, sustainable, affordable and accessible care. An active approach in cost containment of expensive and innovative cancer drugs was adopted in our organisation to safeguard accessibility and improve quality of life for patients. In this article, we described four inverventions: 1) identify right patient and minimise overtreatment, 2) in-house medicine production for selected indications, 3) minimise medicine spillages and 4) effective procurement strategies. We call on other hospitals to take action and, favourably, to collaborate on a European level. Together, we will safeguard the current and future care of our patients.
Language	English
Publishing date	2023-08-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2023.1264951
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Article ; Online: Integrative whole-genome and transcriptome analysis of HER2-amplified metastatic breast cancer.

Verschoor, Noortje / Smid, Marcel / Jager, Agnes / Sleijfer, Stefan / Wilting, Saskia M / Martens, John W M

Breast cancer research : BCR

2023 Volume 25, Issue 1, Page(s) 145

Abstract: Background: In breast cancer, the advent of anti-HER2 therapies has made HER2+ tumors a highly relevant subgroup. However, the exact characteristics which prohibit clinical response to anti-HER2 therapies and drive disease progression are not yet fully ... ...

Abstract	Background: In breast cancer, the advent of anti-HER2 therapies has made HER2+ tumors a highly relevant subgroup. However, the exact characteristics which prohibit clinical response to anti-HER2 therapies and drive disease progression are not yet fully known. Integrative whole-genome and transcriptomic sequencing data from both primary and metastatic HER2-positive breast cancer will enhance our understanding of underlying biological processes. Methods: Here, we used WGS and RNA sequencing data of 700 metastatic breast tumors, of which 68 being HER2+, to search for specific genomic features of HER2+ disease and therapy resistance. Furthermore, we integrated results with transcriptomic data to associate tumors exhibiting a HER2+-specific gene expression profile with ERBB2 mutation status, prior therapy and relevant gene expression signatures. Results: Overall genomic profiles of primary and metastatic HER2+ breast cancers were similar, and no specific acquired genomics traits connected to prior anti-HER2 treatment were observed. However, specific genomic features were predictive of progression-free survival on post-biopsy anti-HER2 treatment. Furthermore, a HER2-driven expression profile grouped HER2-amplified tumors with ERBB2-mutated cases and cases without HER2 alterations. The latter were reported as ER positive in primary disease, but the metastatic biopsy showed low ESR1 expression and upregulation of the MAPK pathway, suggesting transformation to ER independence. Conclusions: In summary, although the quantity of variants increased throughout HER2-positive breast cancer progression, the genomic composition remained largely consistent, thus yielding no new major processes beside those already operational in primary disease. Our results suggest that integrated genomic and transcriptomic analyses may be key in establishing therapeutic options.
MeSH term(s)	Humans ; Female ; Breast Neoplasms/pathology ; Receptor, ErbB-2/genetics ; Receptor, ErbB-2/metabolism ; Mutation ; Gene Expression Profiling/methods ; Genomics/methods ; Transcriptome ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism
Chemical Substances	Receptor, ErbB-2 (EC 2.7.10.1) ; Biomarkers, Tumor
Language	English
Publishing date	2023-11-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2015059-3
ISSN	1465-542X ; 1465-5411
ISSN (online)	1465-542X
ISSN	1465-5411
DOI	10.1186/s13058-023-01743-z
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Zs.A 5494: Show issues

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Jg. 1995 - 2021: Lesesall (2.OG)
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Article ; Online: Physicians' Perspectives on Ethical Issues Regarding Expensive Anti-Cancer Treatments: A Qualitative Study.

Bomhof, Charlotte H C / Schermer, Maartje / Sleijfer, Stefan / Bunnik, Eline M

AJOB empirical bioethics

2022 Volume 13, Issue 4, Page(s) 275–286

Abstract: Background: When anti-cancer treatments have been given market authorization, but are not (yet) reimbursed within a healthcare system, physicians are confronted with ethical dilemmas. Arranging access through other channels, e.g., hospital budgets or ... ...

Abstract	Background: When anti-cancer treatments have been given market authorization, but are not (yet) reimbursed within a healthcare system, physicians are confronted with ethical dilemmas. Arranging access through other channels, e.g., hospital budgets or out-of-pocket payments by patients, may benefit patients, but leads to unequal access. Until now, little is known about the perspectives of physicians on access to non-reimbursed treatments. This interview study maps the experiences and moral views of Dutch oncologists and hematologists. Methods: A diverse sample of oncologists and hematologists (n = 22) were interviewed. Interviews were analyzed thematically using Nvivo 12 qualitative data software. Results: This study reveals stark differences between physicians' experiences and moral views on access to anti-cancer treatments that are not (yet) reimbursed: some physicians try to arrange other ways of access and some physicians do not. Some physicians inform patients about anti-cancer treatments that are not yet reimbursed, while others wait for reimbursement. Some physicians have principled moral objections to out-of-pocket payment, while others do not. Conclusion: Oncologists and hematologists in the Netherlands differ greatly in their perspectives on access to expensive anti-cancer treatments that are not (yet) reimbursed. As a result, they may act differently when confronted with dilemmas in the consultation room. Physicians working in different healthcare systems may face similar dilemmas.
MeSH term(s)	Humans ; Qualitative Research ; Physicians ; Morals ; Netherlands
Language	English
Publishing date	2022-08-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2763190-4
ISSN	2329-4523 ; 2329-4515
ISSN (online)	2329-4523
ISSN	2329-4515
DOI	10.1080/23294515.2022.2110963
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Zs.A 6890: Show issues

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Article ; Online: Phase II studies in soft tissue sarcoma: time for reappraisal.

Sleijfer, Stefan

The oncologist

2012 Volume 17, Issue 2, Page(s) 154–156

MeSH term(s)	Antineoplastic Agents/therapeutic use ; Benzenesulfonates/therapeutic use ; Female ; Hemangiosarcoma/drug therapy ; Humans ; Male ; Niacinamide/analogs & derivatives ; Phenylurea Compounds ; Pyridines/therapeutic use ; Sorafenib
Chemical Substances	Antineoplastic Agents ; Benzenesulfonates ; Phenylurea Compounds ; Pyridines ; Niacinamide (25X51I8RD4) ; Sorafenib (9ZOQ3TZI87)
Language	English
Publishing date	2012-01-27
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	1409038-7
ISSN	1549-490X ; 1083-7159
ISSN (online)	1549-490X
ISSN	1083-7159
DOI	10.1634/theoncologist.2011-0382
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Zs.A 4845: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 494: Show issues

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Article ; Online: EJC's biennial report on metastatic soft tissue sarcoma: State of the art and future perspectives.

Vos, Melissa / Sleijfer, Stefan

European journal of cancer (Oxford, England : 1990)

2018 Volume 88, Page(s) 87–91

Abstract: In the last decade the limited treatment options for patients with metastatic soft tissue sarcoma have expanded considerably. With the addition of olaratumab to first-line treatment with doxorubicin, the introduction of several new agents in second-line ... ...

Abstract	In the last decade the limited treatment options for patients with metastatic soft tissue sarcoma have expanded considerably. With the addition of olaratumab to first-line treatment with doxorubicin, the introduction of several new agents in second-line treatment and beyond and other promising agents in the pipeline, perspectives of patients with metastatic soft tissue sarcoma are improving. Due to increasing insight into the biology of the different soft tissue sarcoma subtypes, choice of treatment has become much more histology-driven, although more prognostic and predictive factors are needed to further personalise therapy. This report summarises the current state of the art and discusses the promising developments in the treatment of patients with metastatic soft tissue sarcoma.
MeSH term(s)	Antibodies, Monoclonal/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Dioxoles/administration & dosage ; Doxorubicin/administration & dosage ; Drug Therapy/methods ; Drug Therapy/trends ; Forecasting ; Humans ; Neoplasm Metastasis ; Pyrimidines/administration & dosage ; Sarcoma/drug therapy ; Sarcoma/pathology ; Sulfonamides/administration & dosage ; Tetrahydroisoquinolines/administration & dosage
Chemical Substances	Antibodies, Monoclonal ; Dioxoles ; Pyrimidines ; Sulfonamides ; Tetrahydroisoquinolines ; pazopanib (7RN5DR86CK) ; Doxorubicin (80168379AG) ; trabectedin (ID0YZQ2TCP) ; olaratumab (TT6HN20MVF)
Language	English
Publishing date	2018
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	82061-1
ISSN	1879-0852 ; 0277-5379 ; 0959-8049 ; 0964-1947
ISSN (online)	1879-0852
ISSN	0277-5379 ; 0959-8049 ; 0964-1947
DOI	10.1016/j.ejca.2017.10.020
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Zs.A 456: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 583: Show issues

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Article ; Online: Non-Coding RNAs, a Novel Paradigm for the Management of Gastrointestinal Stromal Tumors.

Amirnasr, Azadeh / Sleijfer, Stefan / Wiemer, Erik A C

International journal of molecular sciences

2020 Volume 21, Issue 18

Abstract: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal malignancies found in the gastrointestinal tract. At a molecular level, most GISTs are characterized by gain-of-function mutations in V-Kit Hardy-Zuckerman 4 Feline Sarcoma Viral ... ...

Abstract	Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal malignancies found in the gastrointestinal tract. At a molecular level, most GISTs are characterized by gain-of-function mutations in V-Kit Hardy-Zuckerman 4 Feline Sarcoma Viral Oncogene Homolog (
MeSH term(s)	Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Gastrointestinal Stromal Tumors/genetics ; Gastrointestinal Stromal Tumors/metabolism ; Gastrointestinal Stromal Tumors/pathology ; Gastrointestinal Stromal Tumors/therapy ; Humans ; Imatinib Mesylate/therapeutic use ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Proto-Oncogene Proteins c-kit/genetics ; Proto-Oncogene Proteins c-kit/metabolism ; RNA, Neoplasm/genetics ; RNA, Neoplasm/metabolism ; Receptor, Platelet-Derived Growth Factor beta/genetics ; Receptor, Platelet-Derived Growth Factor beta/metabolism
Chemical Substances	Biomarkers, Tumor ; MicroRNAs ; RNA, Neoplasm ; Imatinib Mesylate (8A1O1M485B) ; KIT protein, human (EC 2.7.10.1) ; PDGFRB protein, human (EC 2.7.10.1) ; Proto-Oncogene Proteins c-kit (EC 2.7.10.1) ; Receptor, Platelet-Derived Growth Factor beta (EC 2.7.10.1)
Language	English
Publishing date	2020-09-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21186975
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