Nitroglycerin as a radiosensitizer in non-small cell lung cancer: Results of a prospective imaging-based phase II trial
| Autor: | Marike W. van Gisbergen, Erik Vegt, Joachim E. Wildberger, Felix M. Mottaghy, Catharina M.L. Zegers, Dirk De Ruysscher, Bart Reymen, Ala Yaromina, Philippe Lambin, Wouter van Elmpt, Ludwig Dubois, Aniek J.G. Even, Marco Das |
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| Přispěvatelé: | Radiotherapie, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Precision Medicine, RS: FSE DACS IDS, Institute of Data Science, Beeldvorming, MUMC+: DA Beeldvorming (5), RS: Carim - B06 Imaging, RS: GROW - R2 - Basic and Translational Cancer Biology, Radiology & Nuclear Medicine, Radiotherapy |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
HX4-HV
HX4 hypoxic volume medicine.medical_treatment R895-920 HYPOXIA NSCLC 030218 nuclear medicine & medical imaging TTD total tumour dose chemistry.chemical_compound Nitroglycerin Medical physics. Medical radiology. Nuclear medicine 0302 clinical medicine NECK-CANCER Clinical endpoint Medicine SUVmax maximum standardised uptake value MFS metastasis-free survival RC254-282 HX4 GTV gross tumour volume Neoplasms. Tumors. Oncology. Including cancer and carcinogens GTVp gross tumour volume of the primary tumour HX4-HF HX4 hypoxic fraction CHEMOTHERAPY 3. Good health TBR tumour-to-blood ratio Mitochondria Perfusion Oncology 030220 oncology & carcinogenesis HX4 2-nitroimidazole [18F]-HX4 (flortanidazole 3-[18F]fluoro-2-(4-((2-nitro-1Himidazol-1-yl)methyl)-1H-1 2 3-triazol-1-yl)-propan-1-ol) cardiovascular system medicine.symptom circulatory and respiratory physiology RADIOTHERAPY Radiosensitizer medicine.medical_specialty FHV fraction of hypoxic volume hypoxic fraction of the GTV Urology LRPFS loco-regional progression free survival Article PET positron emission tomography OS overall survival 03 medical and health sciences SDG 3 - Good Health and Well-being NSCLC non-small cell lung cancer CoR coefficient of repeatability Radiology Nuclear Medicine and imaging cardiovascular diseases Lung cancer BV blood volume IQR interquartile range Chemotherapy NO nitric oxide CARBOPLATIN NITRIC-OXIDE business.industry CONCURRENT INDAR individualized accelerated radiotherapy BF blood flow STAGE IIIA Hypoxia (medical) medicine.disease Carboplatin respiratory tract diseases DCE-CT dynamic contrast-enhanced CT Radiation therapy CI confidence interval PET chemistry GTVln gross tumour volume of the lymph nodes SUVmean mean standardised uptake value business |
| Zdroj: | Clinical and Translational Radiation Oncology, Vol 21, Iss, Pp 49-55 (2020) Clinical and Translational Radiation Oncology, 21, 49-55. Elsevier Ireland Ltd Clinical and Translational Radiation Oncology |
| ISSN: | 2405-6308 0121-0378 |
| Popis: | Highlights • Nitroglycerin didn’t improve overall survival of NSCLC patients. • The toxicity of combining nitroglycerin with standard treatment was mild. • Increased uptake of HX4 showed negative prognostic significance in NSCLC patients. • Tumor perfusion after nitroglycerin treatment did not correlate with outcome. Background Nitroglycerin is proposed as an agent to reduce tumour hypoxia by improving tumour perfusion. We investigated the potential of nitroglycerin as a radio-sensitizer in non-small cell lung cancer (NSCLC) and the potential of functional imaging for patient selection. Material and methods Trial NCT01210378 is a single arm phase II trial, designed to detect 15% improvement in 2-year overall survival (primary endpoint) in stage IB-IV NSCLC patients treated with radical (chemo-) radiotherapy and a Transiderm-Nitro 5 patch during radiotherapy. Patients underwent dynamic contrast-enhanced CTs (DCE-CT) and HX4 (hypoxia) PET/CTs before and after nitroglycerin. Secondary endpoints were progression-free survival, toxicity and the prognostic value of tumour perfusion/hypoxia at baseline and after nitroglycerin. Results The trial stopped after a futility analysis after 42 patients. At median follow-up of 41 months, two-year and median OS were 58% (95% CI: 44–78%) and 38 months (95% CI: 22–54 months), respectively. Nitroglycerin could not reduce tumour hypoxia. DCE-CT parameters did not correlate with OS, whereas hypoxic tumours had a worse OS (p = 0.029). Changes in high-uptake fraction of HX4 and tumour blood flow were negatively correlated (r = -0.650, p = 0.022). The heterogeneity in treatment modalities and patient characteristics combined with a small sample size made further subgroup analysis of survival results impossible. Toxicity related to nitroglyerin was limited to headache (17%) and hypotension (2.4%). Conclusion Nitroglycerin did not improve OS of NSCLC patients treated with (chemo-)radiotherapy. A general ability of nitroglycerin to reduce hypoxia was not shown. |
| Databáze: | OpenAIRE |
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