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Tumor Hypoxia on 18F-Fluoromisonidazole Positive Emission Tomography as a Predictor of Distant Metastasis-Free Survival after Chemoradiation for Head and Neck Squamous Cell Carcinoma: A Pooled Analysis of Clinical Trials.

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Title: Tumor Hypoxia on 18F-Fluoromisonidazole Positive Emission Tomography as a Predictor of Distant Metastasis-Free Survival after Chemoradiation for Head and Neck Squamous Cell Carcinoma: A Pooled Analysis of Clinical Trials.
Authors: Gui, C.1 (AUTHOR), Wray, R.2 (AUTHOR), Schoder, H.2 (AUTHOR), Grkovski, M.3 (AUTHOR), Humm, J.2 (AUTHOR), Wong, R.J.4 (AUTHOR), Sherman, E.5 (AUTHOR), Riaz, N.1 (AUTHOR), Lee, N.Y.1 (AUTHOR)
Source: International Journal of Radiation Oncology, Biology, Physics. 2024 Supplement, Vol. 120 Issue 2, pS130-S131. 2p.
Subjects: Squamous cell carcinoma, Patient selection, Overall survival, Tumor classification, Hypoxemia
Abstract: High rates of locoregional control are observed after chemoradiation (CRT) for head and neck squamous cell carcinoma (HNSCC), but distant metastasis (DM) remains a major cause of morbidity and mortality. Improved prediction of adverse oncologic outcomes would facilitate patient selection for escalated therapy. Prior studies have shown that tumor hypoxia on FMISO PET predicts for local failure after CRT, but data showing an association with DM are limited. We combined data from two clinical trials to evaluate whether tumor hypoxia on FMISO PET predicts DM-free survival (DMFS) and overall survival (OS) after CRT for HNSCC. From 2004 to 2020, patients undergoing CRT for nonmetastatic HNSCC who enrolled on two clinical trials investigating the role of FMISO PET (NCT00606294, NCT03323463) were included in this analysis. FMISO PET before and ≥ 7 days after starting CRT were evaluated for tumor hypoxia. Pre- and intra-treatment hypoxia were hypothesized to predict worse DMFS and OS, measured from the end of CRT. DMFS was defined using a composite endpoint, consisting of biopsy-proven HNSCC outside the head and neck or death. Predictors of DMFS and OS were modeled with Cox regression. Among 295 patients, 86% had oropharyngeal primaries, and 89% had HPV+ disease. Per AJCC 7th edition staging, 15% had T ≥ 3, and 18% had N ≥ 2c. De-escalated 30 Gy CRT was delivered to 49% of patients; all others received 70 Gy CRT. Pre- and intra-treatment hypoxia on FMISO PET were identified in 218 (74%) and 69 (23%) patients, respectively. Median follow-up among survivors was 4.4 years. DMFS and OS at 4 years were 89% and 94%, respectively. Among 17 patients with DM, 4 had prior locoregional recurrence. Among 69 patients negative for pre-treatment hypoxia, none experienced DM. In univariable models, worse DMFS was associated with pre-treatment hypoxia (HR 3.37, 95% CI = 1.03-11.1, p = 0.04) and intra-treatment hypoxia (HR 2.57, 95% CI = 1.28-5.15, p = 0.008). In a multivariable model, intra-treatment hypoxia independently predicted worse DMFS (HR 2.94, 95% CI = 1.40-6.21, p = 0.005), alongside T ≥ 3 disease. In univariable models, trends toward worse OS were seen with pre-treatment hypoxia (HR 2.76, 95% CI = 0.84-9.08, p = 0.09) and intra-treatment hypoxia (HR 1.76, 95% CI = 0.85-3.61, p = 0.13). We report the largest clinical series evaluating tumor hypoxia on FMISO PET as a predictor for DMFS and OS after CRT for HNSCC. Pre- and intra-treatment hypoxia on FMISO PET significantly predicted worse DMFS. Intra-treatment hypoxia predicted worse DMFS independent of tumor stage. No patients who were negative for hypoxia on pre-treatment FMISO PET experienced DM. Tumor hypoxia on FMISO PET may aid in selecting patients for escalated treatment strategies aimed at preventing DM. [ABSTRACT FROM AUTHOR]
Copyright of International Journal of Radiation Oncology, Biology, Physics is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Tumor Hypoxia on 18F-Fluoromisonidazole Positive Emission Tomography as a Predictor of Distant Metastasis-Free Survival after Chemoradiation for Head and Neck Squamous Cell Carcinoma: A Pooled Analysis of Clinical Trials.
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  Data: <searchLink fieldCode="JN" term="%22International+Journal+of+Radiation+Oncology%2C+Biology%2C+Physics%22">International Journal of Radiation Oncology, Biology, Physics</searchLink>. 2024 Supplement, Vol. 120 Issue 2, pS130-S131. 2p.
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  Data: <searchLink fieldCode="DE" term="%22Squamous+cell+carcinoma%22">Squamous cell carcinoma</searchLink><br /><searchLink fieldCode="DE" term="%22Patient+selection%22">Patient selection</searchLink><br /><searchLink fieldCode="DE" term="%22Overall+survival%22">Overall survival</searchLink><br /><searchLink fieldCode="DE" term="%22Tumor+classification%22">Tumor classification</searchLink><br /><searchLink fieldCode="DE" term="%22Hypoxemia%22">Hypoxemia</searchLink>
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  Label: Abstract
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  Data: High rates of locoregional control are observed after chemoradiation (CRT) for head and neck squamous cell carcinoma (HNSCC), but distant metastasis (DM) remains a major cause of morbidity and mortality. Improved prediction of adverse oncologic outcomes would facilitate patient selection for escalated therapy. Prior studies have shown that tumor hypoxia on FMISO PET predicts for local failure after CRT, but data showing an association with DM are limited. We combined data from two clinical trials to evaluate whether tumor hypoxia on FMISO PET predicts DM-free survival (DMFS) and overall survival (OS) after CRT for HNSCC. From 2004 to 2020, patients undergoing CRT for nonmetastatic HNSCC who enrolled on two clinical trials investigating the role of FMISO PET (NCT00606294, NCT03323463) were included in this analysis. FMISO PET before and ≥ 7 days after starting CRT were evaluated for tumor hypoxia. Pre- and intra-treatment hypoxia were hypothesized to predict worse DMFS and OS, measured from the end of CRT. DMFS was defined using a composite endpoint, consisting of biopsy-proven HNSCC outside the head and neck or death. Predictors of DMFS and OS were modeled with Cox regression. Among 295 patients, 86% had oropharyngeal primaries, and 89% had HPV+ disease. Per AJCC 7th edition staging, 15% had T ≥ 3, and 18% had N ≥ 2c. De-escalated 30 Gy CRT was delivered to 49% of patients; all others received 70 Gy CRT. Pre- and intra-treatment hypoxia on FMISO PET were identified in 218 (74%) and 69 (23%) patients, respectively. Median follow-up among survivors was 4.4 years. DMFS and OS at 4 years were 89% and 94%, respectively. Among 17 patients with DM, 4 had prior locoregional recurrence. Among 69 patients negative for pre-treatment hypoxia, none experienced DM. In univariable models, worse DMFS was associated with pre-treatment hypoxia (HR 3.37, 95% CI = 1.03-11.1, p = 0.04) and intra-treatment hypoxia (HR 2.57, 95% CI = 1.28-5.15, p = 0.008). In a multivariable model, intra-treatment hypoxia independently predicted worse DMFS (HR 2.94, 95% CI = 1.40-6.21, p = 0.005), alongside T ≥ 3 disease. In univariable models, trends toward worse OS were seen with pre-treatment hypoxia (HR 2.76, 95% CI = 0.84-9.08, p = 0.09) and intra-treatment hypoxia (HR 1.76, 95% CI = 0.85-3.61, p = 0.13). We report the largest clinical series evaluating tumor hypoxia on FMISO PET as a predictor for DMFS and OS after CRT for HNSCC. Pre- and intra-treatment hypoxia on FMISO PET significantly predicted worse DMFS. Intra-treatment hypoxia predicted worse DMFS independent of tumor stage. No patients who were negative for hypoxia on pre-treatment FMISO PET experienced DM. Tumor hypoxia on FMISO PET may aid in selecting patients for escalated treatment strategies aimed at preventing DM. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of International Journal of Radiation Oncology, Biology, Physics is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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      – TitleFull: Tumor Hypoxia on 18F-Fluoromisonidazole Positive Emission Tomography as a Predictor of Distant Metastasis-Free Survival after Chemoradiation for Head and Neck Squamous Cell Carcinoma: A Pooled Analysis of Clinical Trials.
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