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Phase III Randomized Trial of Very Accelerated Radiation Therapy Compared With Conventional Radiation Therapy in Squamous Cell Head and Neck Cancer: A GORTEC Trial

Jean Bourhis, Michel Lapeyre, Jacques Tortochaux, Michel Rives, Mehdi Aghili, Sylvain Bourdin, François Lesaunier, Toufik Benassi, Claire Lemanski, Lionel Geoffrois, Antoine Lusinchi, Pierre Verrelle, Etienne Bardet, Morbize Julieron, Pierre Wibault, Monique Luboinski, Ellen Benhamou

From the Institut Gustave Roussy, Radiation Oncology, Head and Neck Statistics Departments, Villejuif; Centre Alexis Vautrin, Nancy; Centre Jean Perrin, Clermont-Ferrand; Centre Claudius Regaud, Toulouse; Centre René Gauducheau, Nantes; Centre Francois Baclesse, Caen; Centre Hospitalier, Lagny; and the Centre Val D'aurelle, Montpellier, France

Address reprint requests to Jean Bourhis, MD, PhD, Department of Radiation-Oncology, Gustave Roussy Institute, 39 rue Camille Desmoulins, 94805 Villejuif, France; e-mail: bourhis{at}igr.fr

	ABSTRACT

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PURPOSE: With the aim to increase the dose intensity of radiation therapy (RT), and subsequently the locoregional control rate, a very accelerated RT regimen was compared with conventional RT in a series of patients with head and neck squamous cell carcinoma (HNSCC).

PATIENTS AND METHODS: Between 1994 and 1998, 268 patients with T3 or T4, N0 to N3 HNSCC (staged by 1997 International Union Against Cancer criteria) that was not eligible for surgery were randomly assigned to receive either conventional RT, delivering 70 Gy in 7 weeks to the primary tumor and 35 fractions of 2 Gy over 49 days, or to receive very accelerated RT, delivering 62 to 64 Gy in 31 to 32 fractions of 2 Gy over 22 to 23 days (2 Gy/fraction bid).

RESULTS: The most common tumor site was the oropharynx and most of the patients (70%) had T4 and N1 to N3 tumors in 72% of patients. The main patient and tumor characteristics were well-balanced between the two arms. The median total doses were 63 Gy (accelerated) and 70 Gy (conventional), with a median overall time of 22 days and 48 days, respectively. Acute mucositis was markedly increased in the accelerated-RT arm (P < .001). The locoregional control rate was improved by 24% at 6 years with accelerated RT. In contrast, disease-free survival and overall survival were not significantly different between the two arms. There was no difference in late effects between the two arms.

CONCLUSION: The very accelerated RT regimen was feasible and provided a major benefit in locoregional control but had a modest effect on survival.

	INTRODUCTION

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More than 500,000 head and neck squamous cell carcinomas (HNSCC) are diagnosed worldwide each year, most of them being locally advanced at presentation.¹ The treatment of HNSCC is generally based on surgery and radiation therapy, which allows for locoregional control rates of 70% to 80% in early-stage carcinoma (stages I to II, 1997 International Union Against Cancer [UICC] staging system), but is markedly inferior in the locally advanced stages (UICC stages III and IV). Because radiation therapy plays a key role in the management of these cancers, several approaches have been developed to improve its efficacy, while maintaining acceptable toxicities. Among them, the addition of concomitant chemotherapy has been shown to improve survival, compared with radiotherapy alone.^2-7 The magnitude of the benefit associated with the use of chemotherapy (CT), evaluated from more than 10,000 patients entered onto 63 randomized trials (Meta-Analysis of Chemotherapy in Head and Neck Cancer [MACH-NC] database) was 4%, being more pronounced for concomitant radiotherapy (RT) -CT (8% at 5 years).⁷

An alternative to RT-CT has been to use altered fractionated RT. Indeed, a considerable interest has been focused in the last decades on the possibilities of improving the efficacy of radiotherapy when using altered fractionated radiotherapy. Altered fractionated RT aims to increase the dose intensity of RT by delivering a total dose as high as possible in an overall time that is as short as possible. This increased dose intensity of RT can be obtained either by increasing the total dose (hyperfractionation) and/or decreasing the overall time (acceleration) compared with the dose and schedule for conventional RT. These recent advances were made possible because of a better understanding of the parameters of fractionation (total dose, dose per fraction, interval between fraction, and overall treatment time) involved in determining acute normal tissue reactions (mucositis, epithelitis), as well as the late effects (fibrosis, necrosis). Decreasing the dose per fraction (< 1.2 Gy) can protect late-responding normal tissues more than tumor cells, leading to a differential effect that allows the delivery of a total dose that is higher than the conventional dose in the same overall time and constitutes the basis of hyperfractionated RT.^8-11

More recently, accelerated RT schedules have been developed with the aim to overcome tumor cell repopulation during the course of radiotherapy.^5,12-21 Another argument to evaluate accelerated RT in HNSCC is related to the rapid tumor cell kinetics of these cancers, with a potential doubling time of less than 3 days in the majority of cases.^22,23 Several randomized trials have compared conventional RT to accelerated RT in HNSCC. In some of these trials, a significant improvement in local control was evident in the accelerated arm, without a significant gain in overall survival.¹⁹ Large variations of the overall treatment time have been reported from 1 week to more than 5 weeks of reduction of the overall time. The total dose was kept the same when moderate acceleration was used (1 to 2 weeks), whereas with stronger degrees of acceleration, the total dose was reduced in order to avoid unacceptable acute toxicity.^5,15-17,24 This dose reduction had been reported in the Continuous Hyperfractionated Accelerated Radiotherapy (CHART) trial,²⁴ and more recently in the Trans-Tasman Radiation Oncology Group (TROG) trial,¹⁵ which used doses of 54 Gy and 59 Gy, respectively. In both trials, only a marginal benefit was seen in favor of the accelerated arm, suggesting that the total dose might have been too low to obtain a significant benefit on tumor control. In contrast with these studies, in a phase II study we previously reported on the feasibility of using very accelerated RT while maintaining the total dose at higher levels.^12-14 In this randomized study, we have further studied this very accelerated regimen, and compared it with conventional RT in a series of patients with locally advanced HNSCC.

	PATIENTS AND METHODS

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Inclusion Criteria
Patients were eligible if they had no previous history of cancer and/or previous RT or chemotherapy treatment, and if they had a performance status of 0 to 2 (WHO scoring system). After a pan-endoscopy under general anesthesia, a computed tomography scan and/or magnetic resonance imaging scan of the head and neck, and a metastatic work-up (lung, liver), the patient's eligibility was assessed by a multidisciplinary committee composed of a head and neck surgeon, a radiation oncologist, and a medical oncologist. Patients with a T3 or T4, N0 to N3 (UICC 1997 staging system) squamous cell carcinoma of the head and neck (oropharynx, oral cavity, hypopharynx, or larynx) were eligible. All patients had to have a disease that was not eligible for surgery, either because of locoregional extension and/or because of poor general condition. Signed informed consent for each patient was obtained before random assignment.

Treatment
Patients were randomly assigned to receive either conventional RT, delivering 70 Gy to the primary tumor over 7 weeks and 35 fractions of 2 Gy in 49 days, or very accelerated RT, delivering 62 to 64 Gy in 31 to 32 fractions over 22 to 23 days (2 Gy/fraction bid). The interval between fractions in the accelerated arm was at least 8 hours. In both arms, the dose was calculated in accordance with International Commission on Radiation Units and Measurements (ICRU) Report 50. A 4-MV linac or cobalt 60 irradiation were used along with conventional treatment planning system (no 3-dimensional conformal RT or intensity-modulated radiation therapy was used). The spinal cord exclusion was performed at 34 Gy in the accelerated arm and at 42 Gy in the conventional arm, and cervical posterior nodes were treated thereafter with electron beams of appropriate energy (8 to 12 MeV). Prophylactic nodal irradiation dose was 45 Gy in the accelerated arm and 50 Gy in the conventional arm.

Randomization
Patients fulfilling enrolment criteria were centrally randomized by phone (at the Institute Gustave Roussy, Villejuif, France). Treatment arm assignments (conventional RT v very accelerated RT) were allocated from a computer-generated list stratified by center.

Sample Size and Statistical Analysis
It was estimated that a minimum of 100 patients per group would be necessary to demonstrate an increase of the locoregional tumor control rate, from 30% in the conventional group to 55% in the very accelerated group, with = 5% and ß = 5% (two-tailed test).

Analyses were carried out on the intent-to-treat principle. Differences between groups were evaluated by ² test or Fisher's exact test for categoric variables and t test for continuous variables (two-sided tests). The survival probabilities were estimated according to the Kaplan-Meier method. The curves carry Rothman's 95% CIs. Survival curves were compared by the logrank test, and the Cox proportional hazards model was used to estimate the risk ratio of events after controlling for prognostic variables.

	RESULTS

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Patient Characteristics
Between November 1994 and September 1998, 268 patients were included in this study from 11 French cancer centers of the Groupe Oncologie Radiotherapie Tête et Cou (GORTEC). The analysis was performed for 266 patients because of missing data for one patient and because another patient refused treatment soon after random assignment. Of the 266 remaining patients, 129 were randomly assigned to conventional RT and 137 patients were assigned to accelerated RT.

The main initial characteristics of the patients included are listed in Table 1, showing that the most common tumor site was the oropharynx. The distribution of the patients according to the tumor and nodal stage is shown in Tables 1 and 2. Most of the patients had T4 disease and a nodal involvement was found in most patients. The distribution of the main patient and tumor characteristics was well-balanced between both study arms, although more advanced nodal involvement was observed in the accelerated arm (this difference between the two arms was of borderline significance for some items: fixity, nodal size, ulceration).

Quality Assurance for Radiotherapy
The characteristics of each individual treatment were reviewed by a panel consisting of investigators and external experts who examined the medical charts twice a year throughout the study period. Ninety-five percent of the medical charts were reviewed by this panel. The total dose, the duration of radiotherapy, the dose per fraction, and the dose distributions were checked, along with the verification of the fields of irradiation. The tumor and nodal extension were also checked and restaged when appropriate.

The total dose was scored as correct, with less than 5% deviation in 93% of patients on the accelerated arm and 91% of patients on the conventional arm. A minor deviation (between 5% and 10%) was observed in 1% and 2% of patients in the accelerated and conventional arms, respectively, whereas a major deviation (dose received varied > 10% of the protocol's stipulation) was observed in 6% and 7% of the accelerated arm and the conventional RT arms, respectively (definitive treatment interruptions).

Regarding the overall duration of radiotherapy, the treatment was shorter than initially planned in 8% of the accelerated-arm patients and 30% of the conventional-arm patients (frequently, slightly less than 48 hours). The abbreviated treatment was judged to be in keeping with the panel guidelines in 74% of the patients on the accelerated arm and 66% of the patients on the conventional arm. A minor deviation from the planned schedule (overall time > 5 to 10 days) occurred more frequently in the accelerated arm (13% v 3%). Similarly, a major deviation from the planned schedule (overall time > 10 days) occurred more frequently in the accelerated arm (6% v 1%).

Acute Toxicity
The main acute toxicity was related to mucosal reactions. In order to assess this acute mucositis, both the WHO and the RTOG (Radiation Therapy Oncology Group) scoring systems were used. A more severe and more prolonged mucositis was observed in the patients treated with accelerated RT, as listed in Table 3. Indeed, most of the patients in the accelerated arm had WHO grade 3 (liquid) or grade 4 (aphagia) toxicities, whereas based on the RTOG scoring system, most of the patients had grade 3 confluent mucositis. These acute mucosal reactions related to the accelerated RT regimen took a mean time of 2.5 months to heal. The other acute toxicities, especially the skin toxicity, were similar in both arms of the study (Table 3).

Tumor Control and Survival
The locoregional control rate was significantly better in the accelerated-RT arm, as shown in Figure 1. At 2 years, a 24% improvement was seen in favor of the accelerated arm (P < .01), which was maintained at 5 years. In contrast, disease-free survival and overall survival were not significantly different between the two arms, although the results were in favor of the accelerated-RT arm, as shown in Figure 2.

View larger version (9K): [in this window] [in a new window]   Fig 1. Locoregional control. RT, radiation therapy.

View larger version (9K): [in this window] [in a new window]   Fig 2. Overall survival. RT, radiation therapy.

Late Effects
Late toxicity was assessed throughout the follow-up period, using the European Organisation for Research and Treatment of Cancer (EORTC) -RTOG scoring system. With a median follow-up of more than 6 years, there was no difference in late effects between the two arms for all the items considered, that is, neck fibrosis, bone necrosis, myelitis (0% in both arms), mucosal necrosis, and so on (Table 6).

View this table: [in this window] [in a new window]   Table 6. Late Effects Toxicity Grade 3 After 3 Months (RTOG criteria)

	DISCUSSION

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... Author Contributions REFERENCES

 
We report here for the first time the results of a randomized trial that evaluates the effect of a very intense radiotherapy regimen. Interestingly, the long follow-up period allows us to present mature data, especially on late effects associated with radiotherapy.

Altered-fractionation RT has been shown to be a possible treatment option to improve the efficacy of RT in advanced HNSCC. However, little is known about the possibility to maintain a relatively high total dose when using a very accelerated regimen. The regimen tested in this study is one of the most intense ones reported so far, and proved to be feasible on a multi-institutional basis.

As expected, based on experiences in previous reports,^12-14 acute toxicity was a major concern, with confluent mucositis in most patients that was associated with prolonged time for healing (average, 2.5 months). The use of a feeding tube was mandatory for most of the patients in the accelerated-RT arm.

In contrast, no increase in late effects was observed, suggesting that the overall treatment time may influence the acute toxicity more than the late effects. Indeed, late effects may be more related to other parameters such as the dose per fraction, the interval between fraction and the total dose.^8,11,16,24 Among these three parameters, the dose per fraction was maintained at a high level, but the two other factors were designed to minimize the risk of late effects. Indeed, a relatively large interval between fractions was used (> 8 to 9 hours), and the total dose was reduced compared with conventional RT.

Regarding the selection of the patients, most of the cases in both arms were strictly unresectable, but a slight imbalance regarding nodal extension was found in favor of the patients on the conventional-RT arm. Despite that, the accelerated RT provided a major benefit in terms of locoregional control, however, it led to a modest effect on survival. This discrepancy between the marked benefit observed in locoregional control and the limited effect on survival has already been reported in HNSCC.¹⁹ When using very accelerated RT, it may be important to keep the total dose as high as reasonably achievable, because previous studies that used relatively lower total doses of RT on very accelerated schedules (CHART²⁴: 54 Gy in 12 days; TROG¹⁵: 59.5 Gy in 4 weeks) failed to show a significant benefit on tumor control, although they showed a trend in favor of the accelerated RT. In contrast, using higher total doses associated with strong acceleration schedules, such as in the EORTC 22851 trial¹⁶ (72 Gy in 5 weeks) and in the Vancouver trial¹⁷ (66 Gy in 3.5 weeks), may increase acute toxicity, as seen in our study, but may also increase late effects. However, a potential confounding factor that may have influenced late toxicity in the Vancouver trial was surgery, since most of the cases of severe toxicity were reported in patients who underwent salvage surgery.

Whether the type of very accelerated RT we used is any better than less intense modified-fractionated RT, especially hyperfractionated schedules that seemed promising in a recent meta-analysis,¹⁸ is not known and would need to be studied.

The standard of care used in this study may appear in 2006 to be questionable, since conventional RT alone is no longer considered as a reference arm.^7,18 However, when our trial began in 1994, it was not clear whether alternative treatment could be better than conventional RT. With that aim in mind, we initiated in 1994 two randomized trials within the GORTEC group, comparing conventional RT to concomitant RT-CT^3,6 and a second trial to very accelerated RT.

It is also not known how this very intense RT regimen may compare with concomitant RT-CT, which has regularly been shown to be superior to conventional RT alone in advanced HNSCC.⁷ This issue is being addressed in an ongoing GORTEC randomized study (99-02 trial).

	Authors' Disclosures of Potential Conflicts of Interest

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... Author Contributions REFERENCES

 
The authors indicated no potential conflicts of interest.

	Author Contributions

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... Author Contributions REFERENCES

 

Conception and design: Jean Bourhis, Michel Lapeyre, Pierre Verrelle, Etienne Bardet, Ellen Benhamou Provision of study materials or patients: Jean Bourhis, Michel Lapeyre, Jacques Tortochaux, Michel Rives, Sylvain Bourdin, Toufik Benassi, Claire Lemanski, Lionel Geoffrois, Pierre Verrelle, Etienne Bardet, Morbize Julieron, Pierre Wibault, Antoine Lusinchi Collection and assembly of data: Jean Bourhis, Michel Lapeyre, Jacques Tortochaux, Michel Rives, Mehdi Aghili, François Lesaunier, Pierre Verrelle, Morbize Julieron, Monique Luboinski, Ellen Benhamou Data analysis and interpretation: Jean Bourhis, Michael Lapeyre, Ellen Benhamou Manuscript writing: Jean Bourhis, Lionel Geoffrois, Antoine Lusinchi, Pierre Wibault, Ellen Benhamou Final approval of manuscript: Jean Bourhis, Michel Rives, Sylvain Bourdin, Claire Lemanski, Lionel Geoffrois, Antoine Lusinchi, Pierre Verrelle, Etienne Bardet, Morbize Julieron, Pierre Wibault, Monique Luboinski, Ellen Benhamou Other: Toufik Benassi [Investigation]

 

	ACKNOWLEDGMENTS

 
We thank the external review experts J.J. Mazeron, MD, V. Grégoire, MD, PhD, P. Maingon, MD, P. Pommier, MD, for their review, and we thank Ana Chauvain for her contribution in preparing the manuscript.

	NOTES

 
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

	REFERENCES

TOP ABSTRACT INTRODUCTION PATIENTS AND METHODS RESULTS DISCUSSION Authors' Disclosures of... Author Contributions REFERENCES

 
1. Ferlay J, Bray F, Pisani P, et al: GLOBOCAN 2000: Cancer Incidence, Mortality and Prevalence Worldwide, Version 1.0. IARC CancerBase No. 5. Lyon, France, IARC Press, 2001

2. Bourhis J, Pignon JPP: Meta-analyses in head and neck squamous cell carcinoma: What is the role of chemotherapy? Hematol Oncol Clin North Am 13:769-775, 1999[CrossRef][Medline]

3. Calais G, Alfonsi M, Bardet E, et al: Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma. J Natl Cancer Inst 91:2081-2086, 1999[Abstract/Free Full Text]

4. Brizel DM, Alsbers M, Fisher S: Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer. N Engl J Med 338:1798-1804, 1998[Abstract/Free Full Text]

5. Dobrowsky W, Dobrowsky E, Naudé J, et al: Conventional versus accelerated in advanced head and neck cancer. Br J Cancer Suppl 74:S279-S281, 1996 (suppl)

6. Denis F, Garaud P, Bardet E, et al: Late toxicity results of the GORTEC 94-01 randomized trial comparing radiation therapy with concomitant radio-chemotherapy for advanced-stage oropharynx carcinoma: Comparison of LENT/SOMA, RTOG/EORTC and NCI/CTC scoring systems. Int J Radiat Oncol Biol Phys 55:93-98, 2003[CrossRef][Medline]

7. Pignon JP, Bourhis J, Domenge C, et al: Meta-analysis of chemotherapy in head and neck squamous cell carcinoma: On behalf of the MACH-NC collaborative group. Lancet 355:949-955, 2000[Medline]

8. Horiot JC, LeFur R, N'Guyen T, et al: Hyperfractionation versus conventional fractionation in oropharyngeal carcinoma: Final analysis of a randomized trial of the EORTC cooperative group of radiotherapy. Radiother Oncol 25:231-241, 1992[CrossRef][Medline]

9. Datta NR, Dutta Choudhry A, Gupta S, et al: Twice a day versus once a day radiation therapy in head and neck cancer. Int J Radiat Oncol Biol Phys 17:132, 1989 (suppl 1; abstr 35)

10. Pinto LHJ, Canary PCV, Araujo CMM, et al: Prospective randomized trial comparing hyperfractionated versus conventional radiotherapy in stage III and IV oropharyngeal carcinoma. Int J Radiat Oncol Biol Phys 21:557-562, 1991[Medline]

11. Fu KK, Pajak TF, Trotti A, et al: A radiation therapy oncology group (RTOG) phase III randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas: First report of RTOG 9003. Int J Radiat Oncol Biol Phys 48:7-16, 2000[CrossRef][Medline]

12. Bourhis J, Fortin A, Dupuis O, et al: Very accelerated radiotherapy : Preliminary results in locally unresectable head and neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys 32:747-752, 1995[CrossRef][Medline]

13. Bourhis J, Wibault P, Eschwege F: Very accelerated fractionation. Int J Radiat Oncol Biol Phys 32:889-890, 1995[CrossRef][Medline]

14. Bourhis J, De Crevoisier R, Wibault P, et al: A randomized study of very accelerated radiotherapy with and without amifostine in head and neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys 46:1105-1108, 2000[CrossRef][Medline]

15. Poulsen MG, Denham JW, Peters LJ, et al: A randomised trial of accelerated and conventional radiotherapy for stage III and IV squamous carcinoma of the head and neck: A Trans-Tasman Radiation Oncology Group Study. Radiother Oncol 60:113-122, 2001[CrossRef][Medline]

16. Horiot JC, Bontemps P, van den Bogaert W, et al: Accelerated fractionation compared to conventional fractionation improves locoregional control in the radiotherapy of advanced head and neck cancer: Results of the EORTC 22851 randomized trial. Radiother Oncol 44:111-121, 1997[CrossRef][Medline]

17. Jackson SM, Weir LM, Hay JH, et al: Randomized trial of accelerated versus conventional radiotherapy in head and neck cancer. Radiother Oncol 43:39-46, 1997[CrossRef][Medline]

18. Bourhis J, Syz N, Overgaard J, et al: Conventional vs modified fractionated radiotherapy: Meta-analysis of radiotherapy in head and neck carcinoma—A meta-analysis based on individual patient data. Int J Radiat Oncol Biol Phys 54:71-72, 2002 (suppl; abstr 119)

19. Overgaard J, Hansen HS, Specht L, et al: Five compared with six fractions per week of conventional radiotherapy of squamous-cell carcinoma of head and neck: DAHANCA 6 and 7 randomised controlled trial. Lancet 362:933-940, 2003[CrossRef][Medline]

20. Skladowski K, Maciejewski B, Golen M, et al: Randomized clinical trial on 7-days continuous accelerated irradiation (CAIR) of head and neck cancer: Report on 3-year tumor control and normal tissue toxicity. Radiother Oncol 55:101-110, 2000[CrossRef][Medline]

21. Hliniak A, Gwiazdowska B, Szutkowski Z, et al: A multicentre randomized/controlled trial of a conventional versus modestly accelerated radiotherapy in the laryngeal cancer: Influence of a 1 week shortening overall time. Radiother Oncol 62:1-10, 2002[CrossRef][Medline]

22. Bourhis J, Dendale R, Hill C, et al: Potential doubling time and clinical outcome in head and neck carcinoma treated with 70 Gy/7 weeks. Int J Radiat Oncol Biol Phys 35:471-476, 1996[CrossRef][Medline]

23. Ang K, Trotti A, Garden A, et al: Importance of overall time factor in post-operative radiotherapy. Proceedings of the 4th International Conference on Head and Neck Cancer, July 28-August 1, 1996, pp 231-235

24. Dische S, Saunders M, Barrett A, et al: A randomized multicentre trial of CHART vs conventional radiotherapy in head and neck cancer. Radiother Oncol 44:123-136, 1997[CrossRef][Medline]

Submitted August 7, 2004; accepted March 17, 2006.

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This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bourhis, J. Articles by Benhamou, E. Search for Related Content PubMed PubMed Citation Articles by Bourhis, J. Articles by Benhamou, E. Social Bookmarking                            What's this?