Repopulation of FaDu human squamous cell carcinoma during fractionated radiotherapy correlateswith reoxygenation

Petersen, Cordula; Zips, Daniel; Krause, Mechthild; Schöne, Kerstin; Eicheler, Wolfgang; Hoinkis, Cordelia; Thames, Howard D.; Baumann, Michaël

doi:10.1016/s0360-3016(01)01686-8

Cited by 98 publications

(64 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Withers et al [21] proposed a period of up to 4 weeks between initiation of RT and the onset of accelerated repopulation in tumours. More recent papers, however, appear to support a lag time of around 3 weeks [5], and this is also supported by data from Petersen et al [22], who found a relationship between reduction in hypoxia and the onset of proliferation after 22 days. It should be stated, however, that there is no fixed lag period before the onset of proliferation that has been established.…”

Section: -Specificitymentioning

confidence: 61%

Predictive value of modelled tumour control probability based on individual measurements ofin vitroradiosensitivity and potential doubling time

Hedman¹,

Björk‐Eriksson²,

Brodin³

et al. 2013

BJR

View full text Add to dashboard Cite

Objective: The aim of this study was to compare patient-specific radiobiological parameters with population averages in predicting the clinical outcome after radiotherapy (RT) using a tumour control probability (TCP) model based on the biological effective dose (BED).Methods: A previously published study of 46 head and neck carcinomas with individually identified radiobiological parameters, radiosensitivity and potential doubling time (T pot ), and known tumour size was investigated. These patients had all been treated with external beam RT, and the majority had also received brachytherapy. The TCP for each individual based on the BED using patient-specific radiobiological parameters was compared with the TCP based on the BED using average radiobiological parameters (a50.3 Gy 21 , T pot 53 days).Results: 43 patients remained in the final analysis. There was only a weak trend for increasing local tumour control with increasing BED in both groups. However, when the TCP was calculated, the use of patientspecific parameters was better for identifying local control correctly. The sensitivity and specificity for tumour-specific parameters

show abstract

Section: -Specificitymentioning

confidence: 61%

Predictive value of modelled tumour control probability based on individual measurements ofin vitroradiosensitivity and potential doubling time

Hedman¹,

Björk‐Eriksson²,

Brodin³

et al. 2013

BJR

View full text Add to dashboard Cite

show abstract

“…22) and this may also differ between tumors of the same histopathologic type (23). In addition, CSC-related radiobiologic mechanisms such as repopulation during treatment and recovery from radiation-induced damage between the single fractions have been shown to increase tumor resistance against radiotherapy (24)(25)(26).…”

Section: Translational Relevancementioning

confidence: 99%

Low Cancer Stem Cell Marker Expression and Low Hypoxia Identify Good Prognosis Subgroups in HPV(−) HNSCC after Postoperative Radiochemotherapy: A Multicenter Study of the DKTK-ROG

Linge

Löck

Gudziol

et al. 2016

Clinical Cancer Research

Self Cite

117

143

View full text Add to dashboard Cite

Purpose: To investigate the impact of hypoxia-induced gene expression and cancer stem cell (CSC) marker expression on outcome of postoperative cisplatin-based radiochemotherapy (PORT-C) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC).Experimental Design: Expression of the CSC markers CD44, MET, and SLC3A2, and hypoxia gene signatures were analyzed in the resected primary tumors using RT-PCR and nanoString technology in a multicenter retrospective cohort of 195 patients. CD44 protein expression was further analyzed in tissue microarrays. Primary endpoint was locoregional tumor control.Results: Univariate analysis showed that hypoxia-induced gene expression was significantly associated with a high risk of locoregional recurrence using the 15-gene signature (P ¼ 0.010) or the 26-gene signature (P ¼ 0.002). In multivariate analyses, in patients with HPV16 DNA-negative but not with HPV16 DNA-positive tumors the effect of hypoxia-induced genes on locoregional control was apparent (15-gene signature: HR 4.54, P ¼ 0.006; 26-gene signature: HR 10.27, P ¼ 0.024). Furthermore, MET, SLC3A2, CD44, and CD44 protein showed an association with locoregional tumor control in multivariate analyses (MET: HR 3.71, P ¼ 0.016; SLC3A2: HR 8.54, P ¼ 0.037; CD44: HR 3.36, P ¼ 0.054; CD44 protein n/a because of no event in the CD44-negative group) in the HPV16 DNA-negative subgroup.Conclusions: We have shown for the first time that high hypoxia-induced gene expression and high CSC marker expression levels correlate with tumor recurrence after PORT-C in patients with HPV16 DNA-negative HNSCC. After validation in a currently ongoing prospective trial, these parameters may help to further stratify patients for individualized treatment de-escalation or intensification strategies.

show abstract

“…Although the number of tumor cells is greatly reduced during cytotoxic treatment, cells that survive are triggered to repopulate more effectively during the intervals between treatments, and this process of repopulation is an important cause of treatment failure (10,11,35,36). Randomized trials have convincingly shown that accelerated radiotherapy, that is, delivery of the radiation dose in a shorter time, can counteract accelerated repopulation and improve the tumor control probability (37,38).…”

Section: Dose Escalation To Highly Proliferative Subvolumesmentioning

confidence: 99%

¹⁸F-FLT PET/CT for Early Response Monitoring and Dose Escalation in Oropharyngeal Tumors

Troost¹,

Bussink²,

Hoffmann³

et al. 2010

J Nucl Med

143

View full text Add to dashboard Cite

Accelerated tumor cell proliferation is an important mechanism adversely affecting therapeutic outcome in head and neck cancer. 39-deoxy-39-18 F-fluorothymidine ( 18 F-FLT) is a PET tracer to noninvasively image tumor cell proliferation. The aims of this study were to monitor early tumor response based on repetitive 18 F-FLT PET/CT scans and to identify subvolumes with high proliferative activity eligible for dose escalation. Methods: Ten patients with oropharyngeal tumors underwent an 18 F-FLT PET/CT scan before and twice during radiotherapy. The primary tumor and metastatic lymph nodes (gross tumor volume, or GTV) were delineated on CT (GTV CT ) and after segmentation of the PET signal using the 50% isocontour of the maximum signal intensity or an adaptive threshold based on the signal-to-background ratio (GTV SBR ). GTVs were calculated, and similarity between GTV CT and GTV SBR was assessed. Within GTV SBR , the maximum and mean standardized uptake value (SUV max and SUV mean , respectively) was calculated. Within GTV CT , tumor subvolumes with high proliferative activity based on the 80% isocontour (GTV 80% ) were identified for radiotherapy planning with dose escalation. Results: The GTV CT decreased significantly in the fourth week but not in the initial phase of treatment. SUV max and SUV mean decreased significantly as early as 1 wk after therapy initiation and even further before the fourth week of treatment. For the primary tumor, the average (6SD) SUV mean of the GTV SBR was 4.7 6 1.6, 2.0 6 0.9, and 1.3 6 0.2 for the consecutive scans (P , 0.0001). The similarity between GTV CT and GTV SBR decreased during treatment, indicating an enlargement of GTV SBR outside GTV CT caused by the increasing difficulty of segmenting tracer uptake in the tumor from the background and by proliferative activity in the nearby tonsillar tissue. GTV 80% was successfully identified in all primary tumors and metastatic lymph nodes, and dose escalation based on the GTV 80% was demonstrated to be technically feasible. Conclusion: 18 F-FLT is a promising PET tracer for imaging tumor cell proliferation in head and neck carcinomas. Signal changes in 18 F-FLT PET precede volumetric tumor response and are therefore suitable for early response assessment. Definition of tumor subvolumes with high proliferative activity and dose escalation to these regions are technically feasible.

show abstract

Repopulation of FaDu human squamous cell carcinoma during fractionated radiotherapy correlateswith reoxygenation

Cited by 98 publications

References 29 publications

Predictive value of modelled tumour control probability based on individual measurements ofin vitroradiosensitivity and potential doubling time

Predictive value of modelled tumour control probability based on individual measurements ofin vitroradiosensitivity and potential doubling time

Low Cancer Stem Cell Marker Expression and Low Hypoxia Identify Good Prognosis Subgroups in HPV(−) HNSCC after Postoperative Radiochemotherapy: A Multicenter Study of the DKTK-ROG

¹⁸F-FLT PET/CT for Early Response Monitoring and Dose Escalation in Oropharyngeal Tumors

Contact Info

Product

Resources

About

Repopulation of FaDu human squamous cell carcinoma during fractionated radiotherapy correlateswith reoxygenation

Cited by 98 publications

References 29 publications

Predictive value of modelled tumour control probability based on individual measurements ofin vitroradiosensitivity and potential doubling time

Predictive value of modelled tumour control probability based on individual measurements ofin vitroradiosensitivity and potential doubling time

Low Cancer Stem Cell Marker Expression and Low Hypoxia Identify Good Prognosis Subgroups in HPV(−) HNSCC after Postoperative Radiochemotherapy: A Multicenter Study of the DKTK-ROG

18F-FLT PET/CT for Early Response Monitoring and Dose Escalation in Oropharyngeal Tumors

Contact Info

Product

Resources

About

¹⁸F-FLT PET/CT for Early Response Monitoring and Dose Escalation in Oropharyngeal Tumors