The value of plasma hypoxia markers for predicting imaging-based hypoxia in patients with head-and-neck cancers undergoing definitive chemoradiation

Rühle, Alexander; Grosu, A.L.; Wiedenmann, Nicole; Ruf, Juri; Bieber, Birgit; Stoian, Raluca; Thomsen, Andreas; Gkika, Eleni; Vaupel, Peter; Baltas, Dimos; Mix, Michael; Nicolay, Nils H.

doi:10.1016/j.ctro.2022.02.008

Cited by 3 publications

(3 citation statements)

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“…Osteopontin is involved in several pathways related to proliferation, angiogenesis and immunosuppression in cancers including HNSCC [ 56 ]. Furthermore, both intratumoral and plasma osteopontin have been linked to tumor hypoxia, and secretion of osteopontin is increased in senescence-associated T cells, therefore considered as immunosenescence marker [ 44 , 45 , 47 , 51 , 57 ]. To the best of our knowledge, this is the first report about an association between tissue osteopontin levels and patient age among elderly HNSCC patients.…”

Section: Discussionmentioning

confidence: 99%

“…TIM3, LAG3 and CD96 are other ICs that are intensively studied as potential targets in preclinical studies and clinical trials [39][40][41][42][43]. While plasma levels of osteopontin, a bone sialoprotein, have shown to exhibit predictive value regarding tumor hypoxia and the potential benefit of the hypoxia modifier nimorazole [44,45], osteopontin was also found to be abundantly secreted by immunosenescent T cells [46,47].…”

Section: Introductionmentioning

confidence: 99%

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Prognostic value of tumor-infiltrating immune cells and immune checkpoints in elderly head-and-neck squamous cell carcinoma patients undergoing definitive (chemo)radiotherapy

et al. 2022

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Background and purpose Tumor-infiltrating lymphocytes (TILs) are associated with locoregional control (LRC) in head-and-neck squamous cell carcinoma (HNSCC) patients undergoing (chemo)radiotherapy. As immunosenescence results in reduced immune activity, the role of TILs in elderly HNSCC patients may differ compared to younger patients, providing a rationale to study the prognostic role of TILs and immune checkpoints (ICs) in this population. Material and methods Sixty-three HNSCC patients aged ≥ 65 years undergoing definitive (chemo)radiotherapy between 2010 and 2019 with sufficient material from pre-treatment biopsies were included in the analysis. Immunohistochemical stainings of CD3, CD4, CD8, PD-L1, TIM3, LAG3, TIGIT and CD96, and of osteopontin as an immunosenescence-associated protein were performed. Overall survival (OS) and progression-free survival (PFS) were determined using the Kaplan–Meier method, and Fine-Gray's models were used for locoregional failure (LRF) analyses. Results While there was no correlation between patient age and IC expression, osteopontin levels correlated with increasing age (r = 0.322, p < 0.05). Two-year OS, PFS, and LRC were 44%, 34%, and 71%, respectively. Increased LAG3 expression, both intraepithelial (SHR = 0.33, p < 0.05) and stromal (SHR = 0.38, p < 0.05), and elevated stromal TIM3 expression (SHR = 0.32, p < 0.05) corresponded with reduced LRFs. Absent tumoral PD-L1 expression (TPS = 0%) was associated with more LRFs (SHR = 0.28, p < 0.05). There was a trend towards improved LRF rates in elderly patients with increased intraepithelial CD3 + (SHR = 0.52, p = 0.07) and CD8 + (SHR = 0.52, p = 0.09) TIL levels. Conclusion LAG3, TIM3 and TPS are promising biomarkers in elderly HNSCC patients receiving (chemo)radiotherapy. Considering the frequency of non-cancer related deaths in this population, the prognostic value of these biomarkers primarily relates to LRC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Prognostic value of tumor-infiltrating immune cells and immune checkpoints in elderly head-and-neck squamous cell carcinoma patients undergoing definitive (chemo)radiotherapy

et al. 2022

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“…The nal study [32] in Table 2 investigated the association between [ 18 F]FMISO PET imaging and plasma hypoxia markers (osteopontin, vascular endothelial growth factor (VEGF), galectin-3 and circulating tumour growth factor (CTGF)). The most promising result was obtained with serum osteopontin, a protein whose plasma concentration has been shown to increase in conditions of tumour hypoxia [32]. There was a moderate correlation between osteopontin levels and the baseline hypoxic volume (r=0.579), and residual hypoxia on [ 18 F]FMISO PET imaging (p<0.05) during treatment.…”

Section: Resultsmentioning

confidence: 99%

Is there a role for [18F]FMISO PET to guide dose adaptive radiotherapy in head and neck cancer? A review of the literature.

Sambasivan,

Barrington,

Connor

et al. 2023

Preprint

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Purpose Hypoxia is a major cause of radioresistance in head and neck cancer (HNC), resulting in treatment failure and disease recurrence. 18F-fluoromisonidazole ([18F]FMISO) PET has been proposed as a means of localising intratumoural hypoxia in HNC so that radiotherapy can be specifically escalated in hypoxic regions. This concept may not be deliverable in routine clinical practice, however, given that [18F]FMISO PET is costly, time consuming and difficult to access. The aim of this review was to summarise clinical studies involving [18F]FMISO PET to ascertain whether it can be used to guide radiotherapy treatment in HNC. Methods A comprehensive literature search was conducted on PubMed and Web of Science databases. Studies investigating [18F]FMISO PET in newly diagnosed HNC patients were considered eligible for review. Results We found the following important results from our literature review: 1) Studies have focussed on comparing [18F]FMISO PET to other hypoxia biomarkers, but currently there is no evidence of a strong correlation between [18F]FMISO and these biomarkers. 2) The results of [18F]FMISO PET imaging are not necessarily repeatable, and the location of uptake may vary during treatment. 3) Tumour recurrences do not always occur within the pretreatment hypoxic volume on [18F]FMISO PET. 4) Dose modification studies using [18F]FMISO PET are in a pilot phase and so far, none have demonstrated the efficacy of radiotherapy dose painting according to [18F]FMISO uptake on PET. Conclusions Our results suggest it is unlikely [18F]FMISO PET will be suitable for radiotherapy dose adaptation in HNC in a routine clinical setting. Part of the problem is that hypoxia is a dynamic phenomenon, and thus difficult to delineate on a single scan. Currently, it is anticipated that [18F]FMISO PET will remain useful within the research setting only.

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Is there a role for [18F]-FMISO PET to guide dose adaptive radiotherapy in head and neck cancer? A review of the literature

Sambasivan,

Barrington,

Connor

et al. 2024

Clin Transl Imaging

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Purpose Hypoxia is a major cause of radioresistance in head and neck cancer (HNC), resulting in treatment failure and disease recurrence. 18F-fluoromisonidazole ([18F]FMISO) PET has been proposed as a means of localising intratumoural hypoxia in HNC so that radiotherapy can be specifically escalated in hypoxic regions. This concept may be challenging to implement in routine clinical practice however, given that [18F]FMISO PET is costly, time consuming and difficult to access. The aim of this review was to summarise clinical studies involving [18F]FMISO PET and to appraise the evidence for its role in guiding radiotherapy treatment in HNC. Methods A comprehensive literature search was conducted on PubMed and Web of Science databases. Studies investigating [18F]FMISO PET in newly diagnosed HNC patients were considered eligible for review. Results We found the following important results from our literature review: (1) Studies have demonstrated a correlation between [18F]FMISO PET and other hypoxia biomarkers, although the results are not consistent enough to propose a proxy biomarker of [18F]FMISO PET. (2) [18F]FMISO PET uptake changes during a course of radiotherapy treatment, suggesting that imaging should be repeated during treatment. (3) Tumour recurrences do not always occur within the pretreatment hypoxic volume on [18F]FMISO PET. (4) Dose modification studies using [18F]FMISO PET are in a pilot phase. Conclusions Our results show that currently there is insufficient evidence to propose [18F]FMISO PET for radiotherapy dose adaptation in HNC in a routine clinical setting. Part of the challenge is that hypoxia is a dynamic phenomenon, and thus areas identified on a single scan may not be representative. At present, it is anticipated that [18F]FMISO PET will remain useful within the research setting only.

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The value of plasma hypoxia markers for predicting imaging-based hypoxia in patients with head-and-neck cancers undergoing definitive chemoradiation

Cited by 3 publications

References 75 publications

Prognostic value of tumor-infiltrating immune cells and immune checkpoints in elderly head-and-neck squamous cell carcinoma patients undergoing definitive (chemo)radiotherapy

Prognostic value of tumor-infiltrating immune cells and immune checkpoints in elderly head-and-neck squamous cell carcinoma patients undergoing definitive (chemo)radiotherapy

Is there a role for [18F]FMISO PET to guide dose adaptive radiotherapy in head and neck cancer? A review of the literature.

Is there a role for [18F]-FMISO PET to guide dose adaptive radiotherapy in head and neck cancer? A review of the literature

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