Multimodal evaluation of hypoxia in brain metastases of lung cancer and interest of hypoxia image-guided radiotherapy
Abstract Lung cancer patients frequently develop brain metastases (BM). Despite aggressive treatment including neurosurgery and external-radiotherapy, overall survival remains poor. There is a pressing need to further characterize factors in the microenvironment of BM that may confer resistance to r...
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Nature Portfolio
2021
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oai:doaj.org-article:ee453995c9c84f099bc393bb803de6262021-12-02T15:00:20ZMultimodal evaluation of hypoxia in brain metastases of lung cancer and interest of hypoxia image-guided radiotherapy10.1038/s41598-021-90662-02045-2322https://doaj.org/article/ee453995c9c84f099bc393bb803de6262021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90662-0https://doaj.org/toc/2045-2322Abstract Lung cancer patients frequently develop brain metastases (BM). Despite aggressive treatment including neurosurgery and external-radiotherapy, overall survival remains poor. There is a pressing need to further characterize factors in the microenvironment of BM that may confer resistance to radiotherapy (RT), such as hypoxia. Here, hypoxia was first evaluated in 28 biopsies from patients with non‑small cell lung cancer (NSCLC) BM, using CA-IX immunostaining. Hypoxia characterization (pimonidazole, CA-IX and HIF-1α) was also performed in different preclinical NSCLC BM models induced either by intracerebral injection of tumor cells (H2030-Br3M, H1915) into the cortex and striatum, or intracardial injection of tumor cells (H2030-Br3M). Additionally, [18F]-FMISO-PET and oxygen-saturation-mapping-MRI (SatO2-MRI) were carried out in the intracerebral BM models to further characterize tumor hypoxia and evaluate the potential of Hypoxia-image-guided-RT (HIGRT). The effect of RT on proliferation of BM ([18F]-FLT-PET), tumor volume and overall survival was determined. We showed that hypoxia is a major yet heterogeneous feature of BM from lung cancer both preclinically and clinically. HIGRT, based on hypoxia heterogeneity observed between cortical and striatal metastases in the intracerebrally induced models, showed significant potential for tumor control and animal survival. These results collectively highlight hypoxia as a hallmark of BM from lung cancer and the value of HIGRT in better controlling tumor growth.Aurélien Corroyer-DulmontSamuel ValableJade FantinLaurent ChatreJérôme ToutainSylvain TeulierCéline BazilleElise LetissierJérôme LevalletDidier DivouxMéziane IbazizèneStéphane GuillouetCécile PerrioLouisa BarréSébastien SerresNicola R. SibsonFrançoise ChaponGuénaëlle LevalletMyriam BernaudinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021) |
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Medicine R Science Q |
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Medicine R Science Q Aurélien Corroyer-Dulmont Samuel Valable Jade Fantin Laurent Chatre Jérôme Toutain Sylvain Teulier Céline Bazille Elise Letissier Jérôme Levallet Didier Divoux Méziane Ibazizène Stéphane Guillouet Cécile Perrio Louisa Barré Sébastien Serres Nicola R. Sibson Françoise Chapon Guénaëlle Levallet Myriam Bernaudin Multimodal evaluation of hypoxia in brain metastases of lung cancer and interest of hypoxia image-guided radiotherapy |
| description |
Abstract Lung cancer patients frequently develop brain metastases (BM). Despite aggressive treatment including neurosurgery and external-radiotherapy, overall survival remains poor. There is a pressing need to further characterize factors in the microenvironment of BM that may confer resistance to radiotherapy (RT), such as hypoxia. Here, hypoxia was first evaluated in 28 biopsies from patients with non‑small cell lung cancer (NSCLC) BM, using CA-IX immunostaining. Hypoxia characterization (pimonidazole, CA-IX and HIF-1α) was also performed in different preclinical NSCLC BM models induced either by intracerebral injection of tumor cells (H2030-Br3M, H1915) into the cortex and striatum, or intracardial injection of tumor cells (H2030-Br3M). Additionally, [18F]-FMISO-PET and oxygen-saturation-mapping-MRI (SatO2-MRI) were carried out in the intracerebral BM models to further characterize tumor hypoxia and evaluate the potential of Hypoxia-image-guided-RT (HIGRT). The effect of RT on proliferation of BM ([18F]-FLT-PET), tumor volume and overall survival was determined. We showed that hypoxia is a major yet heterogeneous feature of BM from lung cancer both preclinically and clinically. HIGRT, based on hypoxia heterogeneity observed between cortical and striatal metastases in the intracerebrally induced models, showed significant potential for tumor control and animal survival. These results collectively highlight hypoxia as a hallmark of BM from lung cancer and the value of HIGRT in better controlling tumor growth. |
| format |
article |
| author |
Aurélien Corroyer-Dulmont Samuel Valable Jade Fantin Laurent Chatre Jérôme Toutain Sylvain Teulier Céline Bazille Elise Letissier Jérôme Levallet Didier Divoux Méziane Ibazizène Stéphane Guillouet Cécile Perrio Louisa Barré Sébastien Serres Nicola R. Sibson Françoise Chapon Guénaëlle Levallet Myriam Bernaudin |
| author_facet |
Aurélien Corroyer-Dulmont Samuel Valable Jade Fantin Laurent Chatre Jérôme Toutain Sylvain Teulier Céline Bazille Elise Letissier Jérôme Levallet Didier Divoux Méziane Ibazizène Stéphane Guillouet Cécile Perrio Louisa Barré Sébastien Serres Nicola R. Sibson Françoise Chapon Guénaëlle Levallet Myriam Bernaudin |
| author_sort |
Aurélien Corroyer-Dulmont |
| title |
Multimodal evaluation of hypoxia in brain metastases of lung cancer and interest of hypoxia image-guided radiotherapy |
| title_short |
Multimodal evaluation of hypoxia in brain metastases of lung cancer and interest of hypoxia image-guided radiotherapy |
| title_full |
Multimodal evaluation of hypoxia in brain metastases of lung cancer and interest of hypoxia image-guided radiotherapy |
| title_fullStr |
Multimodal evaluation of hypoxia in brain metastases of lung cancer and interest of hypoxia image-guided radiotherapy |
| title_full_unstemmed |
Multimodal evaluation of hypoxia in brain metastases of lung cancer and interest of hypoxia image-guided radiotherapy |
| title_sort |
multimodal evaluation of hypoxia in brain metastases of lung cancer and interest of hypoxia image-guided radiotherapy |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/ee453995c9c84f099bc393bb803de626 |
| work_keys_str_mv |
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