Predictive assays of radiation response in patients with head and neck squamous cell carcinoma: A review of the institute gustave roussy experience

Eschwège, F.; Bourhis, Jean; Girinski, T; Lartigau, Éric; Guichard, M.; Deblé, David; Kepta, Lucina; Wilson, George D.; Luboinski, B.

doi:10.1016/s0360-3016(97)00509-9

Cited by 57 publications

(35 citation statements)

References 22 publications

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“…The¯ow cytometry data are also consistent with previously published data [2,3,5,9,11,14,18,31,34,43,44,48,49,54]. Just over half the patients were reported as having aneuploid tumors, and the aneuploid tumors had faster kinetics (higher LI, shorter Tpot) than the diploid tumors, as reported in other studies [5,8,9,11,14,31,34,47,49,54].…”

Section: Discussionsupporting

confidence: 91%

“…Several studies have employed such methods to assess the predictive value of pre-treatment cell kinetic parameters after radiotherapy [2,3,5,6,11,14,31,34,43,47,54]. Results have been variable, some showing positive association with outcome [3,5,14,47,54], and some not [11,18,31,34,43]. Almost all the studies have included relatively few patients, limiting their power.…”

Section: Introductionmentioning

confidence: 99%

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The value of pretreatment cell kinetic parameters as predictors for radiotherapy outcome in head and neck cancer: a multicenter analysis

Begg

Haustermans

Hart

et al. 1999

Radiotherapy and Oncology

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133

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Purpose: The aim of this study was to assess the potential of pre-treatment cell kinetic parameters to predict outcome in head and neck cancer patients treated by conventional radiotherapy.Materials and methods: Data from 11 different centers were pooled. Inclusion criteria were such that the patients received radiotherapy alone, and that the radiotherapy was given in an overall time of at least 6 weeks with a dose of at least 60 Gy. All patients received a tracer dose of either iododeoxyuridine (IdUrd) or bromodeoxyuridine (BrdUrd) intravenously prior to treatment and a tumor biopsy was taken several hours later. The cell kinetic parameters labeling index (LI), DNA synthesis time (Ts) and potential doubling time (Tpot) were subsequently calculated from¯ow cytometry data, obtained on the biopsies using antibodies against I/BrdUrd incorporated into DNA. Each center carried out their own¯ow cytometry analysis.Results: From the 11 centers, a total of 476 patients conforming to the inclusion criteria were analyzed. Median values for overall time and total dose were 49 days and 69 Gy, respectively. Fifty one percent of patients had local recurrences and 53% patients had died, the majority from their disease. Median follow-up was 20 months; being 30 months for surviving patients. Multivariate analysis revealed that T-stage, maximum tumor diameter, differentiation grade, N-stage, tumor localization and overall time correlated with locoregional control, in decreasing order of signi®cance. For the cell kinetic parameters, univariate analysis showed that only LI was signi®cantly associated with local control (P 0:02), with higher values correlating with a worse outcome. Ts showed some evidence that patients with longer values did worse, but this was not signi®cant (P 0:06). Tpot showed no trend (P 0:8). When assessing survival in a univariate analysis, neither LI nor Tpot associated with outcome (P 0:4, 0.4, respectively). Surprisingly, Ts did correlate with survival, with longer values being worse (P 0:02). In the multivariate analysis of local control, LI lost its signi®cance (P 0:16). Conclusions: The only pretreatment kinetic parameter for which some evidence was found for an association with local control (the best end-point for testing the present hypothesis) was LI, not Tpot, and this evidence disappeared in a multivariate analysis. It therefore appears that pretreatment cell kinetic measurements carried out using¯ow cytometry, only provide a relatively weak predictor of outcome after radiotherapy in head and neck cancer. q

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

The value of pretreatment cell kinetic parameters as predictors for radiotherapy outcome in head and neck cancer: a multicenter analysis

Begg

Haustermans

Hart

et al. 1999

Radiotherapy and Oncology

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133

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“…A clear correlation was found, though it required careful selection of the appropriate cut-off value for SF2 (0.42) to discriminate clearly between good and poor outcomes. A similar result was also obtained, though not consistently in head and neck cancer [13][14][15].…”

Section: Intrinsic Radiosensitivitysupporting

confidence: 78%

Molecular biology: the key to personalised treatment in radiation oncology?

Hirst¹,

Robson²

2010

BJR

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ABSTRACT. We know considerably more about what makes cells and tissues resistant or sensitive to radiation than we did 20 years ago. Novel techniques in molecular biology have made a major contribution to our understanding at the level of signalling pathways. Before the ''New Biology'' era, radioresponsiveness was defined in terms of physiological parameters designated as the five Rs. These are: repair, repopulation, reassortment, reoxygenation and radiosensitivity. Of these, only the role of hypoxia proved to be a robust predictive and prognostic marker, but radiotherapy regimens were nonetheless modified in terms of dose per fraction, fraction size and overall time, in ways that persist in clinical practice today. The first molecular techniques were applied to radiobiology about two decades ago and soon revealed the existence of genes/proteins that respond to and influence the cellular outcome of irradiation. The subsequent development of screening techniques using microarray technology has since revealed that a very large number of genes fall into this category. We can now obtain an adequately robust molecular signature, predicting for a radioresponsive phenotype using gene expression and proteomic approaches. In parallel with these developments, functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) can now detect specific biological molecules such as haemoglobin and glucose, so revealing a 3D map of tumour blood flow and metabolism. The key to personalised radiotherapy will be to extend this capability to the proteins of the molecular signature that determine radiosensitivity. Molecular biology developments have, over the past 20 years, provided us with a remarkable array of techniques, enhancing our understanding of how tumour and normal tissues respond to radiation damage. As these techniques grow increasingly sophisticated, their application should, in theory, present opportunities to improve the effectiveness of radiotherapy.However, as we look at how radiotherapy is performed today we see a discipline founded on 100 years of practice-based, empirical development, recently enhanced by impressive advances in dose delivery and image-guided procedures. These developments have brought us to a point where dose deposition is already highly tailored, to a tolerance of ,2% for most tissues of the body, which is much more accurate than any pharmaceutical agent. Yet, are we really delivering dose where it needs to go for maximal therapeutic gain? Basic radiobiology and the five RsThe interaction of high energy X-ray photons with tissue leads to the ejection of fast electrons from molecules (predominantly water), which in turn go on to generate a wide spectrum of secondary electrons, photons and free radicals. The most reactive of these radicals, OH, is capable of creating further radicals of macromolecules. If these are essential for cellular function, as in the case of DNA, then cell biology will be perturbed and this may lead to cell death.These processes have been known for at leas...

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“…This suggests that the length of the actual radiation treatment time is more significant than the surgery-radiotherapy gap probably due to occurrence of an accelerated repopulation process during the actual postoperative radiation treatment time similar to that thought to occur during radical radiotherapy of HNC (Withers et al, 1988). In case of radical radiotherapy of HNC, the influence of pretreatment tumour proliferation parameters on the treatment outcome is a controversial issue (Awwad et al, 1992;Lochin et al, 1992;Bourhis et al, 1993;Eschwege et al, 1997;Zackrisson et al, 1997;Høyer et al, 1998). A multicenter analysis of 476 patients in which 11 centres participating failed to demonstrate an association (Begg et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Accelerated hyperfractionation (AHF) compared to conventional fractionation (CF) in the postoperative radiotherapy of locally advanced head and neck cancer: influence of proliferation

Awwad¹,

Lotayef²,

Shouman³

et al. 2002

Br J Cancer

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Based on the assumption that an accelerated proliferation process prevails in tumour cell residues after surgery, the possibility that treatment acceleration would offer a therapeutic advantage in postoperative radiotherapy of locally advanced head and neck cancer was investigated. The value of T pot in predicting the treatment outcome and in selecting patients for accelerated fractionation was tested. Seventy patients with (T2/N1 -N2) or (T3-4/any N) squamous cell carcinoma of the oral cavity, larynx and hypopharynx who underwent radical surgery, were randomized to either (a) accelerated hyperfractionation: 46.2 Gy per 12 days, 1.4 Gy per fraction, three fractions per day with 6 h interfraction interval, treating 6 days per week or (b) Conventional fractionation: 60 Gy per 6 weeks, 2 Gy per fraction, treating 5 days per week. The 3-year locoregional control rate was significantly better in the accelerated hyperfractionation (88+4%) than in the CF (57+9%) group, P=0.01 (and this was confirmed by multivariate analysis), but the difference in survival (60+10% vs 46+9%) was not significant (P=0.29). The favourable influence of a short treatment time was further substantiated by demonstrating the importance of the gap between surgery and radiotherapy and the overall treatment time between surgery and end of radiotherapy. Early mucositis progressed more rapidly and was more severe in the accelerated hyperfractionation group; reflecting a faster rate of dose accumulation. Xerostomia was experienced by all patients with a tendency to be more severe after accelerated hyperfractionation. Fibrosis and oedema also tended to be more frequent after accelerated hyperfractionation and probably represent consequential reactions. T pot showed a correlation with disease-free survival in a univariate analysis but did not prove to be an independent factor. Moreover, the use of the minimum and corrected P-values did not identify a significant cut-off. Compared to conventional fractionation, accelerated hyperfractionation did not seem to offer a survival advantage in fast tumours though a better local control rate was noted. This limits the use of T pot as a guide for selecting patients for accelerated hyperfractionation. For slowly growing tumours, tumour control and survival probabilities were not significantly different in the conventional fractionation and accelerated hyperfractionation groups. A rapid tumour growth was associated with a higher risk of distant metastases (P=0.01). In conclusion, tumour cell repopulation seems to be an important determinant of postoperative radiotherapy of locally advanced head and neck cancer despite lack of a definite association between T pot and treatment outcome. In fast growing tumours accelerated hyperfractionation provided an improved local control but without a survival advantage. To gain a full benefit from treatment acceleration, the surgery-radiotherapy gap and the overall treatment time should not exceed 6 and 10 weeks respectively.

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Predictive assays of radiation response in patients with head and neck squamous cell carcinoma: A review of the institute gustave roussy experience

Cited by 57 publications

References 22 publications

The value of pretreatment cell kinetic parameters as predictors for radiotherapy outcome in head and neck cancer: a multicenter analysis

The value of pretreatment cell kinetic parameters as predictors for radiotherapy outcome in head and neck cancer: a multicenter analysis

Molecular biology: the key to personalised treatment in radiation oncology?

Accelerated hyperfractionation (AHF) compared to conventional fractionation (CF) in the postoperative radiotherapy of locally advanced head and neck cancer: influence of proliferation

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