Accelerated radiation therapy for locally advanced squamous cell carcinomas of the oral cavity and oropharynx selected according to tumor cell kinetics—A phase II multicenter study

Antognoni, Paolo; Bignardi, Mario; Cazzaniga, L.F.; Poli, Aurélie; Richetti, A.; Bossi, Alberto; Rampello, G.; Barbera, Fernando; Soatti, Carlo Pietro; Bardelli, D; Giordano, Monica; Danova, Marco

doi:10.1016/s0360-3016(96)00403-8

Cited by 20 publications

(13 citation statements)

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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%

“…Values for effective repopulation doubling times (Teff) during the latter part of radiotherapy in head and neck tumors, calculated from retrospective clinical data, are of the order of 4±5 days [20,21,53]. These are in good agreement with Tpot values measured in other series [2,6,11,14,31,34,44,48,49,54], leading to the hypothesis that Tpot may indeed be a predictor of Teff [19], and was the stimulus for carrying out several of the studies contributing to the present analysis. The combined results of 11 studies presented here, however, do not support this hypothesis.…”

Section: Discussionsupporting

confidence: 70%

“…An added advantage is that these methods could be applied after in vivo labeling of the patient with the analogue, avoiding potential in vitro artifacts. 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].…”

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: Discussionsupporting

confidence: 70%

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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“…In a selection of large trials from 1990 to 2004 the average local control (LC) rate for HNSCC was 40-50% (2 Gy per day, 5 days per week for 6.5-8 weeks, i.e. 32-40 fractions and LC rates reported at 2-5 years), with a decrease in LC for advanced stage tumours and for tumours of larger size and faster cell proliferation [13,54,63,[69][70][71]. The total doses from oxic tumour simulations of 69-90 Gy in 6.9-9 weeks were also comparable with the BEDs calculated from HNSCC alternate fractionation clinical trials in the range 63-75 Gy with time correction in the BED formula [59].…”

Section: Comparison Of Hyp-rt Results With Hnscc Clinical Trials and mentioning

confidence: 99%

Monte Carlo radiotherapy simulations of accelerated repopulation and reoxygenation for hypoxic head and neck cancer

Harriss-Phillips

Bezak²,

Yeoh³

2011

BJR

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Objective: A temporal Monte Carlo tumour growth and radiotherapy effect model (HYP-RT) simulating hypoxia in head and neck cancer has been developed and used to analyse parameters influencing cell kill during conventionally fractionated radiotherapy. The model was designed to simulate individual cell division up to 10 8 cells, while incorporating radiobiological effects, including accelerated repopulation and reoxygenation during treatment. Method: Reoxygenation of hypoxic tumours has been modelled using randomised increments of oxygen to tumour cells after each treatment fraction. The process of accelerated repopulation has been modelled by increasing the symmetrical stem cell division probability. Both phenomena were onset immediately or after a number of weeks of simulated treatment. Results: The extra dose required to control (total cell kill) hypoxic vs oxic tumours was 15-25% (8-20 Gy for 562 Gy per week) depending on the timing of accelerated repopulation onset. Reoxygenation of hypoxic tumours resulted in resensitisation and reduction in total dose required by approximately 10%, depending on the time of onset. When modelled simultaneously, accelerated repopulation and reoxygenation affected cell kill in hypoxic tumours in a similar manner to when the phenomena were modelled individually; however, the degree was altered, with non-additive results. Simulation results were in good agreement with standard linear quadratic theory; however, differed for more complex comparisons where hypoxia, reoxygenation as well as accelerated repopulation effects were considered. Conclusion: Simulations have quantitatively confirmed the need for patient individualisation in radiotherapy for hypoxic head and neck tumours, and have shown the benefits of modelling complex and dynamic processes using Monte Carlo methods.

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“…In contrast induction chemotherapy schemes have not achieved a significant improvement of survival [8,13,26,29] but have still a role in laryngeal preservation. Also hyperfractioned and accelerated application of radiotherapy so far have not presented better results than combined chemoradiation [1,2,12]. The efficacy of hyperfractioned radiation and simultaneous chemotherapy is still in evaluation [14].…”

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confidence: 99%

Combined Radiochemotherapy with Docetaxel in Patients with Unresectable Locally Advanced Head and Neck Tumors

Hesse¹,

Heinrich²,

Zimmermann³

et al. 2000

Strahlenther Onkol

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Accelerated radiation therapy for locally advanced squamous cell carcinomas of the oral cavity and oropharynx selected according to tumor cell kinetics—A phase II multicenter study

Cited by 20 publications

References 50 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

Monte Carlo radiotherapy simulations of accelerated repopulation and reoxygenation for hypoxic head and neck cancer

Combined Radiochemotherapy with Docetaxel in Patients with Unresectable Locally Advanced Head and Neck Tumors

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