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Article: Acute polyneuropathy in a metastatic melanoma patient treated with vemurafenib and cobimetinib.

Compter, Annette / Boogerd, Willem / van Thienen, Johannes V / Brandsma, Dieta

2018 Volume 7, Issue 5, Page(s) 418–420

Language	English
Publishing date	2018-03-21
Publishing country	United States
Document type	Case Reports
ZDB-ID	2645818-4
ISSN	2163-0933 ; 2163-0402
ISSN (online)	2163-0933
ISSN	2163-0402
DOI	10.1212/CPJ.0000000000000331
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Article ; Online: Effects of tamoxifen and exemestane on cognitive function in postmenopausal patients with breast cancer.

Lee Meeuw Kjoe, Philippe R / Kieffer, Jacobien M / Small, Brent J / Boogerd, Willem / Schilder, Christina M / van der Wall, Elsken / Meershoek-Klein Kranenbarg, Elma / van de Velde, Cornelis J H / Schagen, Sanne B

JNCI cancer spectrum

2023 Volume 7, Issue 2

Abstract: Background: Cognitive effects of tamoxifen have been described. We augment data from a previous short-term (ST) follow-up study with long-term (LT) data to evaluate ST and LT cognitive effects of tamoxifen followed by exemestane and exemestane in breast ...

Abstract	Background: Cognitive effects of tamoxifen have been described. We augment data from a previous short-term (ST) follow-up study with long-term (LT) data to evaluate ST and LT cognitive effects of tamoxifen followed by exemestane and exemestane in breast cancer patients. Methods: Patients from the Tamoxifen and Exemestane Adjuvant Multinational trial received 5 years exemestane (exemestane group, n = 114) or 2.5 years tamoxifen followed by 2.5 years exemestane (sequential group, n = 92). Neuropsychological performance was assessed pre-endocrine therapy, after 1 year (ST follow-up) and at 5 years (LT follow-up). A control group of healthy participants (n = 120) were assessed with parallel intervals. With random effects modeling we evaluated cognitive changes from baseline to ST and LT follow-up. Statistical tests were 2-sided. Results: After controlling for age, intelligence quotient, attrition, menopausal symptoms, anxiety and/or depression, and/or fatigue, the sequential group showed ST and LT decline compared with control participants on verbal memory (effect size [ES] = 0.26, P = .01; ES = 0.34, P = .003) and executive function (ES = 0.27, P = .007; ES = 0.38, P = .002). Compared with the exemestane group, the sequential group demonstrated ST decline on information processing speed (ES = 0.33, P = .01) and executive function (ES = 0.32, P = .01) and LT decline on verbal memory (ES = 0.33, P = .02). The exemestane group showed no cognitive decline compared with control participants. Conclusion: Cognitive adverse effects of tamoxifen alone and after switching to exemestane were observed, suggestive of a carryover effect of tamoxifen. Our results underline the need for well-controlled, prospective trials studying cognitive effects of endocrine therapy.
MeSH term(s)	Humans ; Female ; Tamoxifen/adverse effects ; Breast Neoplasms/drug therapy ; Breast Neoplasms/psychology ; Follow-Up Studies ; Postmenopause ; Prospective Studies ; Cognition
Chemical Substances	Tamoxifen (094ZI81Y45) ; exemestane (NY22HMQ4BX)
Language	English
Publishing date	2023-03-03
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2515-5091
ISSN (online)	2515-5091
DOI	10.1093/jncics/pkad022
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Article ; Online: PITX2 induction leads to impaired cardiomyocyte function in arrhythmogenic cardiomyopathy.

van Kampen, Sebastiaan J / Han, Su Ji / van Ham, Willem B / Kyriakopoulou, Eirini / Stouthart, Elizabeth W / Goversen, Birgit / Monshouwer-Kloots, Jantine / Perini, Ilaria / de Ruiter, Hesther / van der Kraak, Petra / Vink, Aryan / van Laake, Linda W / Groeneweg, Judith A / de Boer, Teun P / Tsui, Hoyee / Boogerd, Cornelis J / van Veen, Toon A B / van Rooij, Eva

Stem cell reports

2023 Volume 18, Issue 3, Page(s) 749–764

Abstract: Arrhythmogenic cardiomyopathy (ACM) is an inherited progressive disease characterized ...

Abstract	Arrhythmogenic cardiomyopathy (ACM) is an inherited progressive disease characterized by electrophysiological and structural remodeling of the ventricles. However, the disease-causing molecular pathways, as a consequence of desmosomal mutations, are poorly understood. Here, we identified a novel missense mutation within desmoplakin in a patient clinically diagnosed with ACM. Using CRISPR-Cas9, we corrected this mutation in patient-derived human induced pluripotent stem cells (hiPSCs) and generated an independent knockin hiPSC line carrying the same mutation. Mutant cardiomyocytes displayed a decline in connexin 43, NaV1.5, and desmosomal proteins, which was accompanied by a prolonged action potential duration. Interestingly, paired-like homeodomain 2 (PITX2), a transcription factor that acts a repressor of connexin 43, NaV1.5, and desmoplakin, was induced in mutant cardiomyocytes. We validated these results in control cardiomyocytes in which PITX2 was either depleted or overexpressed. Importantly, knockdown of PITX2 in patient-derived cardiomyocytes is sufficient to restore the levels of desmoplakin, connexin 43, and NaV1.5.
MeSH term(s)	Humans ; Myocytes, Cardiac/metabolism ; Connexin 43/genetics ; Connexin 43/metabolism ; Desmoplakins/genetics ; Desmoplakins/metabolism ; Induced Pluripotent Stem Cells/metabolism ; Mutation ; Cardiomyopathies
Chemical Substances	Connexin 43 ; Desmoplakins
Language	English
Publishing date	2023-03-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2720528-9
ISSN	2213-6711 ; 2213-6711
ISSN (online)	2213-6711
ISSN	2213-6711
DOI	10.1016/j.stemcr.2023.01.015
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Article ; Online: Improved Brain Penetration and Antitumor Efficacy of Temozolomide by Inhibition of ABCB1 and ABCG2.

de Gooijer, Mark C / de Vries, Nienke A / Buckle, Tessa / Buil, Levi C M / Beijnen, Jos H / Boogerd, Willem / van Tellingen, Olaf

Neoplasia (New York, N.Y.)

2018 Volume 20, Issue 7, Page(s) 710–720

Abstract: The anticancer drug temozolomide is the only drug with proven activity against high-grade gliomas and has therefore become a part of the standard treatment of these tumors. P-glycoprotein (P-gp; ABCB1) and breast cancer resistance protein (BCRP; ABCG2) ... ...

Abstract	The anticancer drug temozolomide is the only drug with proven activity against high-grade gliomas and has therefore become a part of the standard treatment of these tumors. P-glycoprotein (P-gp; ABCB1) and breast cancer resistance protein (BCRP; ABCG2) are transport proteins, which are present at the blood-brain barrier and limit the brain uptake of substrate drugs. We have studied the effect of P-gp and BCRP on the pharmacokinetics and pharmacodynamics of temozolomide, making use of a comprehensive set of in vitro transport experiments and in vivo pharmacokinetic and antitumor efficacy experiments using wild-type, Abcg2
MeSH term(s)	ATP Binding Cassette Transporter, Sub-Family B/antagonists & inhibitors ; ATP Binding Cassette Transporter, Sub-Family G, Member 2/antagonists & inhibitors ; Animals ; Antineoplastic Agents, Alkylating/pharmacokinetics ; Antineoplastic Agents, Alkylating/pharmacology ; Blood-Brain Barrier/metabolism ; Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/drug therapy ; Brain Neoplasms/metabolism ; Brain Neoplasms/pathology ; Cell Line ; Dacarbazine/analogs & derivatives ; Dacarbazine/pharmacokinetics ; Dacarbazine/pharmacology ; Disease Models, Animal ; Humans ; Magnetic Resonance Imaging ; Male ; Mice ; Neoplasm Proteins/antagonists & inhibitors ; Swine
Chemical Substances	ABCB1 protein, human ; ABCG2 protein, human ; ATP Binding Cassette Transporter, Sub-Family B ; ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; Antineoplastic Agents, Alkylating ; Neoplasm Proteins ; Dacarbazine (7GR28W0FJI) ; temozolomide (YF1K15M17Y)
Language	English
Publishing date	2018-05-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	1483840-0
ISSN	1476-5586 ; 1522-8002
ISSN (online)	1476-5586
ISSN	1522-8002
DOI	10.1016/j.neo.2018.05.001
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Article ; Online: Changes in brain white matter integrity after systemic treatment for breast cancer: a prospective longitudinal study.

Menning, Sanne / de Ruiter, Michiel B / Veltman, Dick J / Boogerd, Willem / Oldenburg, Hester S A / Reneman, Liesbeth / Schagen, Sanne B

Brain imaging and behavior

2018 Volume 12, Issue 2, Page(s) 324–334

Abstract: An increasing number of studies suggest chemotherapy for breast cancer may be neurotoxic. Cross-sectional MRI diffusion tensor imaging (DTI) studies suggest a vulnerability of brain white matter to various chemotherapeutic regimens. Up till now, this was ...

Abstract	An increasing number of studies suggest chemotherapy for breast cancer may be neurotoxic. Cross-sectional MRI diffusion tensor imaging (DTI) studies suggest a vulnerability of brain white matter to various chemotherapeutic regimens. Up till now, this was confirmed in one prospective DTI study: Deprez et al. (2012) showed a widespread decline in fractional anisotropy (FA) of breast cancer patients after chemotherapy consisting of 5-fluorouracil (5-FU), epirubicin and cyclophosphamide (FEC) +/- taxanes +/- endocrine treatment. Our aim was to evaluate whether similar detrimental effects on white matter integrity would be observed with the currently widely prescribed anthracycline-based chemotherapy for breast cancer (predominantly doxorubicin and cyclophosphamide +/- taxanes +/- endocrine treatment (=BC + SYST; n = 26) compared to no systemic treatment (BC; n = 23) and no-cancer controls (NC; n = 30). Assessment took place before and six months after chemotherapy, and matched intervals for the unexposed groups. DTI data were analyzed using voxel-based tract-based spatial statistics and region of interest (ROI) analysis. Voxel-based analysis did not show an effect of chemotherapy +/- endocrine treatment on white matter integrity. ROI analysis however indicated subtle detrimental effects of chemotherapy +/- endocrine treatment by showing a larger decline in WM integrity in the superior longitudinal fasciculus and corticospinal tract in BC + SYST than BC. Indications for relatively mild neurotoxicity in our study might be explained by patient characteristics and specific aspects of data analysis. The omission of 5-FU in current treatment regimens or the administration of doxorubicin instead of epirubicin is also discussed as an explanation for the observed effects.
MeSH term(s)	Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Brain/diagnostic imaging ; Brain/drug effects ; Brain/pathology ; Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/drug therapy ; Cognitive Dysfunction/diagnostic imaging ; Cognitive Dysfunction/etiology ; Cognitive Dysfunction/pathology ; Diffusion Tensor Imaging ; Female ; Humans ; Image Processing, Computer-Assisted ; Middle Aged ; Prospective Studies ; Treatment Outcome ; White Matter/diagnostic imaging ; White Matter/drug effects ; White Matter/pathology
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2018-02-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2377165-3
ISSN	1931-7565 ; 1931-7557
ISSN (online)	1931-7565
ISSN	1931-7557
DOI	10.1007/s11682-017-9695-x
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Article ; Online: Brain Hyperconnectivity >10 Years After Cisplatin-Based Chemotherapy for Testicular Cancer.

Stouten-Kemperman, Myrle M / de Ruiter, Michiel B / Boogerd, Willem / Kerst, J Martijn / Kirschbaum, Clemens / Reneman, Liesbeth / Schagen, Sanne B

Brain connectivity

2018 Volume 8, Issue 7, Page(s) 398–406

Abstract: Chemotherapy for testicular cancer (TC) has been associated with neurotoxic effects shortly post-treatment. Late effects of chemotherapy on brain function in this patient group are still unknown. In this study, we investigated differences between ... ...

Abstract	Chemotherapy for testicular cancer (TC) has been associated with neurotoxic effects shortly post-treatment. Late effects of chemotherapy on brain function in this patient group are still unknown. In this study, we investigated differences between patients with and without chemotherapy in functional brain networks at rest and during an affective processing functional magnetic resonance imaging (fMRI) task on average >14 years post-treatment. In addition, we report on changes in cognitive functioning during survivorship by comparing present and previous performance on a neuropsychological test battery on average 11 years earlier (3 years post-treatment). Twenty-eight chemotherapy (43.1 ± 7.5 years) and 23 surgery-only (48.2 ± 9.5 years) TC survivors were examined using neurocognitive tests and 3T-fMRI >10 years after treatment end. Brain functional networks were identified using dual regression independent component analysis. Task fMRI was analyzed using a block design. Standardized domain change scores were calculated for each individual to assess cognitive change. TC patients in the chemotherapy group showed functional hyperconnectivity at rest in the precuneus network, sensory and motor function network, executive control network, and the ventral stream network when compared with surgery-only patients. Furthermore, hypoactivation was found when performing the affective processing task. Cognitive data revealed that both groups showed comparable patterns of change from 3 to 14 years after initial treatment. This study provides novel insights on the possible underlying neurobiological mechanisms of late neurotoxic effects of cisplatin-based chemotherapy. Present findings reveal that functional hyperconnectivity is widespread, possibly to compensate for the pathophysiological disturbances. This concurs with our previous findings of structural hyperconnectivity in white matter. Longitudinal multimodal imaging studies are warranted to further investigate the association between long-term structural and functional network connectivity data, as well as its relationship with cognitive changes.
MeSH term(s)	Adult ; Antineoplastic Agents/therapeutic use ; Brain/diagnostic imaging ; Brain/drug effects ; Cisplatin/therapeutic use ; Cognition Disorders/drug therapy ; Cognition Disorders/etiology ; Humans ; Image Processing, Computer-Assisted ; Longitudinal Studies ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neural Pathways/diagnostic imaging ; Neural Pathways/drug effects ; Oxygen/blood ; Testicular Neoplasms/complications ; Testicular Neoplasms/drug therapy ; Testicular Neoplasms/pathology ; Tomography Scanners, X-Ray Computed
Chemical Substances	Antineoplastic Agents ; Cisplatin (Q20Q21Q62J) ; Oxygen (S88TT14065)
Language	English
Publishing date	2018-09-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2609017-X
ISSN	2158-0022 ; 2158-0014
ISSN (online)	2158-0022
ISSN	2158-0014
DOI	10.1089/brain.2017.0569
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Article ; Online: Clinical and radiological response of BRAF inhibition and MEK inhibition in patients with brain metastases from BRAF-mutated melanoma.

Geukes Foppen, Marnix H / Boogerd, Willem / Blank, Christian U / van Thienen, Johannes V / Haanen, John B / Brandsma, Dieta

Melanoma research

2018 Volume 28, Issue 2, Page(s) 126–133

Abstract: Patients with brain metastases (BM) from melanoma have an overall survival (OS) of 2-6 months after whole-brain radiotherapy. Targeted therapy (TT) is an effective treatment for BRAF-mutated metastatic melanoma. Moreover, recent studies indicate ... ...

Abstract	Patients with brain metastases (BM) from melanoma have an overall survival (OS) of 2-6 months after whole-brain radiotherapy. Targeted therapy (TT) is an effective treatment for BRAF-mutated metastatic melanoma. Moreover, recent studies indicate intracranial responses of TT in patients with BM. We analyzed 146 patients with BM from BRAF-mutated melanoma treated with vemurafenib, dabrafenib, or dabrafenib+trametinib between 2010 and 2016. We determined clinical and radiological response, progression-free survival (PFS), and OS. Median OS of patients treated with dabrafenib+trametinib was 11.2 months [n=30; 95% confidence interval (CI): 6.8-15.7], 8.8 months for dabrafenib alone (n=31; 95% CI: 3.9-13.7), and 5.7 months for vemurafenib (n=85; 95% CI: 4.6-6.8). A significantly longer OS was observed in the dabrafenib+trametinib group than in the vemurafenib group (hazard ratio for death, 0.52; 95% CI: 0.30-0.89; P=0.02). Median intracranial PFS of all patients was 4.1 months. Median intracranial PFS for patients treated with dabrafenib+trametinib was 5.8 months (95% CI: 3.2-8.5), 5.7 months (95% CI: 3.0-8.4) for dabrafenib, and 3.6 months (95% CI: 3.5-3.8) for vemurafenib (P=0.54). A total of 63 (43%) patients had symptomatic BM. Intracranial disease control rate at 8 weeks in these patients was 65 versus 70% extracranially. Neurological symptoms improved in 46% of patients with symptomatic BM, whereas in 21%, they remained stable. Median OS in patients with BM from BRAF-mutated melanoma treated with dabrafenib+trametinib was significantly longer than for vemurafenib. Improvement of neurological symptoms was seen in almost half of the patients with symptomatic BM treated with TT.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Brain Neoplasms/drug therapy ; Brain Neoplasms/enzymology ; Brain Neoplasms/genetics ; Brain Neoplasms/secondary ; Humans ; Imidazoles/administration & dosage ; Imidazoles/therapeutic use ; MAP Kinase Kinase Kinases/antagonists & inhibitors ; Male ; Melanoma/drug therapy ; Melanoma/enzymology ; Melanoma/pathology ; Middle Aged ; Mutation ; Oximes/administration & dosage ; Oximes/therapeutic use ; Protein Kinase Inhibitors/pharmacology ; Proto-Oncogene Proteins B-raf/antagonists & inhibitors ; Proto-Oncogene Proteins B-raf/genetics ; Pyridones/administration & dosage ; Pyridones/therapeutic use ; Pyrimidinones/administration & dosage ; Pyrimidinones/therapeutic use ; Retrospective Studies ; Skin Neoplasms/drug therapy ; Skin Neoplasms/enzymology ; Skin Neoplasms/genetics ; Skin Neoplasms/pathology ; Treatment Outcome ; Vemurafenib/therapeutic use ; Young Adult
Chemical Substances	Imidazoles ; Oximes ; Protein Kinase Inhibitors ; Pyridones ; Pyrimidinones ; Vemurafenib (207SMY3FQT) ; trametinib (33E86K87QN) ; BRAF protein, human (EC 2.7.11.1) ; Proto-Oncogene Proteins B-raf (EC 2.7.11.1) ; MAP Kinase Kinase Kinases (EC 2.7.11.25) ; dabrafenib (QGP4HA4G1B)
Language	English
Publishing date	2018-01-31
Publishing country	England
Document type	Journal Article ; Observational Study
ZDB-ID	1095779-0
ISSN	1473-5636 ; 0960-8931
ISSN (online)	1473-5636
ISSN	0960-8931
DOI	10.1097/CMR.0000000000000429
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Article ; Online: Neurological immune-related adverse events of ipilimumab.

Bot, Ilja / Blank, Christian U / Boogerd, Willem / Brandsma, Dieta

Practical neurology

2013 Volume 13, Issue 4, Page(s) 278–280

Abstract: Ipilimumab enhances the T lymphocyte mediated immune response to both tumour cells and healthy tissue, improving survival in patients with metastatic melanoma but also leads to more immune-related adverse events (irAEs) than previously used treatments, ... ...

Abstract	Ipilimumab enhances the T lymphocyte mediated immune response to both tumour cells and healthy tissue, improving survival in patients with metastatic melanoma but also leads to more immune-related adverse events (irAEs) than previously used treatments, such as dacarbazine. We present three patients with neurological irAEs from ipilimumab treatment: hypophysitis, meningitis and Guillain-Barré syndrome. Once an irAE occurs, ipilimumab should be stopped and corticosteroids started. Usually, ipilimumab-induced irAE symptoms improve within days to weeks, but can be life-threatening if unrecognised.
MeSH term(s)	Aged ; Antibodies, Monoclonal/therapeutic use ; CTLA-4 Antigen/immunology ; Humans ; Immunologic Factors/therapeutic use ; Ipilimumab ; Male ; Melanoma/drug therapy ; Melanoma/immunology ; Middle Aged
Chemical Substances	Antibodies, Monoclonal ; CTLA-4 Antigen ; Immunologic Factors ; Ipilimumab
Language	English
Publishing date	2013-08
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	2170881-2
ISSN	1474-7766 ; 1474-7758
ISSN (online)	1474-7766
ISSN	1474-7758
DOI	10.1136/practneurol-2012-000447
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Article ; Online: Reaction on the Interpretation of the Hippocampus Avoidance Prophylactic Cranial Irradiation Trial in SCLC (NCT01780675).

Belderbos, José S A / De Ruysscher, Dirk K M / De Jaeger, Katrien / Koppe, Friederike / Lambrecht, Maarten L F / Lievens, Yolande N / Dieleman, Edith M T / Jaspers, Jaap P M / Van Meerbeeck, Jan P / Ubbels, Fred / Kwint, Margriet H / Kuenen, Marianne A / Deprez, Sabine / De Ruiter, Michiel B / Boogerd, Willem / Sikorska, Karolina / Van Tinteren, Harm / Schagen, Sanne B

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

2021 Volume 16, Issue 8, Page(s) e63–e65

MeSH term(s)	Cranial Irradiation/adverse effects ; Hippocampus ; Humans ; Lung Neoplasms/prevention & control ; Small Cell Lung Carcinoma/prevention & control
Language	English
Publishing date	2021-08-04
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2432037-7
ISSN	1556-1380 ; 1556-0864
ISSN (online)	1556-1380
ISSN	1556-0864
DOI	10.1016/j.jtho.2021.06.010
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Article ; Online: Why Did the Randomized Trial of Prophylactic Cranial Irradiation With or Without Hippocampus Avoidance in SCLC Not Reveal a Difference?

Belderbos, José S A / De Ruysscher, Dirk K M / De Jaeger, Katrien / Koppe, Friederike / Lambrecht, Maarten L F / Lievens, Yolande / Dieleman, Edith M T / Jaspers, Jaap P M / Van Meerbeeck, Jan P / Ubbels, Fred / Kwint, Magriet / Kuenen, Marianne / Deprez, Sabine / De Ruiter, Michiel B / Boogerd, Willem / Sikorska, Karolina / Van Tinteren, Harm / Schagen, Sanne B

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

2021 Volume 16, Issue 6, Page(s) e42–e45

MeSH term(s)	Cranial Irradiation/adverse effects ; Hippocampus ; Humans ; Lung Neoplasms ; Small Cell Lung Carcinoma
Language	English
Publishing date	2021-05-25
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2432037-7
ISSN	1556-1380 ; 1556-0864
ISSN (online)	1556-1380
ISSN	1556-0864
DOI	10.1016/j.jtho.2021.03.015
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