Importance of overall treatment time for the outcome of radiotherapy of advanced head and neck carcinoma: dependency on tumor differentiation

Hansen, Olfred; Overgaard, Jens; Hansen, Hanne Sand; Overgaard, Marie; Høyer, Morten; Jørgensen, Karsten; Bastholt, Lars; Berthelsen, A

doi:10.1016/s0167-8140(97)01904-x

Cited by 137 publications

(69 citation statements)

References 22 publications

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“…Recently, it was suggested that well-differentiated carcinomas of the head and neck respond to a radiation trauma with accelerated repopulation just like the normal mucosa, and that these tumours may benefit from reduced overall treatment time (Hansen et al, 1997). In the present study, the poorly differentiated tumours appeared to be the most radiosensitive, measured by tumour cell SF 2 .…”

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confidence: 46%

In vitro radiosensitivity of tumour cells and fibroblasts derived from head and neck carcinomas: mutual relationship and correlation with clinical data

et al. 1999

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SummaryThe aim was to characterize the variation in the cellular in vitro radiosensitivities in squamous cell carcinomas of the head and neck, and to test for a possible correlation between different measures of radiosensitivity and the clinical and histopathological data. Cellular in vitro radiosensitivities were assessed in tumour biopsies from 71 patients using the modified Courtenay-Mills soft agar clonogenic assay combined with an immunocytochemical analysis. Radiosensitivity was quantified as the surviving fraction after a radiation dose of 2 Gy irrespective of cell type (overall SF 2 ), or based on identification of cell type (tumour cell SF 2 , fibroblast SF 2 ). Sixty-three biopsies were from primary tumours, and eight were from recurrences. Overall plating efficiency ranged from 0.005 to 1.60% with a median of 0.052%. The majority of the colonies obtained from the biopsies were fibroblast marker-positive; the proportion of tumour marker-positive colonies ranged from 1 to 88% with a median of 15%. The median overall SF 2 was 0.47 (range 0.24-0.96), the median tumour cell SF 2 was 0.50 (range 0.11-1.0) and the median fibroblast SF 2 was 0.49 (range 0.24-1.0). Comparing data from independent experiments, the overall SF 2 was significantly correlated with the SF 2 of fibroblasts (2P = 0.006) but not with the tumour cell SF 2 . The tumour cell and fibroblast radiosensitivities measured in the same individuals were not correlated (r = 0.06, 95% CI [-0.19, 0.30]). This finding seems to preclude a strong correlation between the radiosensitivity of tumour cells and fibroblasts. Concerning the clinical characteristics, neither of the measures of tumour radiosensitivity was correlated with T-and N-category, stage, tumour size, sex and age. However, the tumour cell radiosensitivity decreased with increasing grade of histopathological differentiation (2P = 0.012). The same tendency was found in two independent analyses of the same patient material. This correlation was not significant in case of the overall SF 2 or the fibroblast SF 2 .Keywords: predictive assays; in vitro radiosensitivity; squamous cell carcinoma of the head and neck; differentiation; fibroblasts; tumour cells 1074British Journal of Cancer (1999) 79(7/8), 1074-1084 © 1999 Cancer Research Campaign Article no. bjoc.1998 Received 11 al, 1991;West et al, 1997), tumour diameter, disease stage and patient age (West et al, 1997).The current report is an extension of a study using the modified CourtenayÐMills soft agar clonogenic assay, to measure in vitro radiosensitivity in squamous cell carcinomas of the head and neck (SCCHN) (Stausb¿l-Gr¿n et al, 1995). This previous study drew attention to the fact that stromal fibroblasts in addition to tumour cells were colony-forming in soft agar. An immunocytochemical analysis was developed to identify the origin of the colonies, and this provided estimates of the radiosensitivity of tumour cells (tumour cell SF 2 ), stromal fibroblasts (fibroblast SF 2 ), and an overall estimate (overall SF 2 ) in the same pat...

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confidence: 46%

In vitro radiosensitivity of tumour cells and fibroblasts derived from head and neck carcinomas: mutual relationship and correlation with clinical data

et al. 1999

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“…Cluster 2 shows also a higher percentage of well-differentiated tumors with respect to the other clusters (Fig. 2); this agrees with a previous study suggesting that welldifferentiated tumors have a more pronounced treatment-time dependency (17). Profile 7 showed benefit also from CHART, but this result was not significant after a multiple test correction.…”

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confidence: 90%

Molecular Marker Profiles Predict Locoregional Control of Head and Neck Squamous Cell Carcinoma in a Randomized Trial of Continuous Hyperfractionated Accelerated Radiotherapy

Buffa

Bentzen

Daley

et al. 2004

Clinical Cancer Research

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Purpose: Identification of factors that assist prediction of tumor response to radiotherapy may aid in refining treatment strategies and improving outcome. Possible association of molecular marker expression profiles with locoregional control of head and neck squamous cell carcinoma was investigated in a randomized trial of conventional versus continuous hyperfractionated accelerated radiotherapy (CHART).Experimental Design: Tumor material was obtained from 402 patients. Immunohistochemistry was used to assess Ki-67, CD31, p53, Bcl-2, and cyclin D1 expression. A hierarchical clustering algorithm with a Bayesian information criterion was used to group tumors with similar marker expression; resulting expression profiles were then compared in terms of their difference in outcome after CHART and conventionally fractionated radiotherapy.Results: Molecular marker profile was an independent prognostic factor for locoregional control. This was confirmed in multivariate analysis, including clinical variables such as tumor and nodal status, primary site, histological grade, age, and gender (P < 0.001 and P ‫؍‬ 0.006 for local and nodal relapse, respectively). In particular, Bcl-2-positive tumors responded significantly better than average in both arms of the trial. Tumors negative for p53-and Bcl-2, with high and randomly patterned Ki-67 expression, responded worse than average with no benefit from CHART. Tumors with similarly negative p53 and Bcl-2, but low Ki-67 staining, with an organized pattern, benefit significantly from CHART schedule.Conclusions: This study demonstrates the potential of molecular profiles to predict radiotherapy response of head and neck squamous cell carcinoma and for treatment stratification. Distinct expression profiles correlate with three distinct clinical phenotypes, including good locoregional control, poor locoregional control, and an outcome strongly dependent upon fractionation schedule.

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“…Well-differentiated squamous cell carcinoma has a shorter potential doubling time and a greater propensity for accelerated repopulation during radiotherapy than most other tumour types [53]. The experiences of the CHART and the DAHANCA studies tend to confirm the benefit of short overall treatment times for well differentiated compared with poorly differentiated squamous cell carcinomas [5,14]. Slevin at al.…”

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confidence: 99%

Three weeks radiotherapy for T1 glottic cancer: the Christie and Royal Marsden Hospital Experience

Gowda¹,

Henk²,

Mais³

et al. 2003

Radiotherapy and Oncology

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Importance of overall treatment time for the outcome of radiotherapy of advanced head and neck carcinoma: dependency on tumor differentiation

Cited by 137 publications

References 22 publications

In vitro radiosensitivity of tumour cells and fibroblasts derived from head and neck carcinomas: mutual relationship and correlation with clinical data

In vitro radiosensitivity of tumour cells and fibroblasts derived from head and neck carcinomas: mutual relationship and correlation with clinical data

Molecular Marker Profiles Predict Locoregional Control of Head and Neck Squamous Cell Carcinoma in a Randomized Trial of Continuous Hyperfractionated Accelerated Radiotherapy

Three weeks radiotherapy for T1 glottic cancer: the Christie and Royal Marsden Hospital Experience

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