Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Fractionated Radiation Therapy in Treating Advanced Squamous Cell Carcinoma of the Head and Neck

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	18 and over	NCI	RTOG-9003 RTOG-90-03, NCT00771641

Objectives

I.  Determine whether hyperfractionation and/or accelerated fractionation 
(split-course or with a concomitant boost) improves the locoregional control 
rate over standard fractionation radiotherapy in patients with advanced 
squamous cell carcinomas of the head and neck.

II.  Determine the disease-free survival and overall survival of these 
patients treated with different radiotherapy fractionation schemes.

III.  Determine the acute and late toxicities of each fractionation schedule.

IV.  Compare the quality of life on the two regimens.

Entry Criteria

Disease Characteristics:

Histologically proven squamous cell carcinoma of the head and neck, including
lymphoepithelioma and anaplastic carcinoma
  Biopsy from the primary or regional nodes acceptable
  No adenocarcinomas

The following stages and sites are eligible:
  Stage III/IV oral cavity, including:
     Anterior 2/3 of the tongue
     Buccal mucosa
     Floor of mouth
     Hard palate
     Gingiva
     Retromolar trigone

  Stage III/IV oropharynx, including:
     Tonsil and pillars
     Faucial arch and soft palate
     Posterolateral pharyngeal walls

  Stage II/III/IV base of the tongue and hypopharynx

  Stage III/IV supraglottic larynx, including:
     Ventricular band
     Arytenoid
     Supra- and infrahyoid epiglottis
     Aryepiglottic fold (tumors at glottic and subglottic
     sites excluded)

Nonpalpable nodes detected only on CT or MRI must be at least 1.0 cm in
diameter or contain necrosis to prove N+ disease

No metastasis below the clavicle clinically or radiologically

Prior/Concurrent Therapy:

Biologic therapy:
  Not specified

Chemotherapy:
  No prior chemotherapy

Endocrine therapy:
  Not specified

Radiotherapy:
  No prior radiotherapy to head and neck
  No planned combined external beam and interstitial boost irradiation

Surgery:
  No prior surgery (other than biopsy)
  No planned combined pre- or postoperative programs
     Radical neck dissections allowed if lymph nodes are greater than 3 cm
     prior to radiotherapy or involvement persists after treatment

     Resection of persistent disease at the primary site may be performed 6
     weeks after completion of radiotherapy

Patient Characteristics:

Age:
  At least 18

Performance status:
  Karnofsky 60-100%

Hematopoietic:
  Not specified

Hepatic:
  Not specified

Renal:
  Not specified

Other:
  Medically able to withstand radiotherapy
  No second malignancy within 5 years except nonmelanomatous skin cancer
  Follow-up by participating radiotherapist required

Expected Enrollment

A total of 1,080 patients (270/arm) will be accrued over 5.75 years.  If 
excessive toxicity is noted in any arm after entry of 324 and 634 patients, 
that arm may be closed.

Outline

Randomized study.

Arm I:  Radiotherapy.  Irradiation of primary tumor and involved and at-risk 
nodal areas using linear accelerators with photon energies of 1.25-6.0 MV 
(dual energy arrangements may also use a beam greater than 6.0 MV), electrons 
of 4-25 MV, or Co60.  Standard fractionation.

Arm II:  Radiotherapy.  Targets and equipment as in Arm I.  Hyperfractionation.

Arm III:  Radiotherapy.  Targets and equipment as in Arm I.  Accelerated 
split-course hyperfractionation.

Arm IV:  Radiotherapy.  Targets and equipment as in Arm I.  Accelerated 
fractionation with concomitant boost.

Konski AA, Winter K, Cole BF, et al.: Quality-adjusted survival analysis of Radiation Therapy Oncology Group (RTOG) 90-03: Phase III randomized study comparing altered fractionation to standard fractionation radiotherapy for locally advanced head and neck squamous cell carcinoma. Head Neck : , 2008.[PUBMED Abstract]

Calvin DP, Hammond ME, Pajak TF, et al.: Microvessel density >or=60 does not predict for outcome after radiation treatment for locally advanced head and neck squamous cell carcinoma: results of a correlative study from the Radiation Therapy Oncology Group (RTOG) 90-03 Trial. Am J Clin Oncol 30 (4): 406-19, 2007.[PUBMED Abstract]

Konski AA, Bhargavan M, Owen J, et al.: Altered fractionated radiotherapy is cost-effective in the treatment of locally advanced head and neck cancer: an economic analysis of Radiation Therapy Oncology Group (RTOG) 90-03. [Abstract] J Clin Oncol 24 (Suppl 18): A-6007, 302s, 2006.

Rabinovitch R, Grant B, Berkey BA, et al.: Impact of nutrition support on treatment outcome in patients with locally advanced head and neck squamous cell cancer treated with definitive radiotherapy: a secondary analysis of RTOG trial 90-03. Head Neck 28 (4): 287-96, 2006.[PUBMED Abstract]

Pajak TF, Trotti A, Gwede CK, et al.: The TAME risk classification system: acute toxicity burden and IPD analysis of RTOG 90-03. [Abstract] Int J Radiat Oncol Biol Phys 63 (2 Suppl 1): A-217, S131, 2005.

Trotti A, Fu KK, Pajak TF, et al.: Long term outcomes of RTOG 90-03: a comparison of hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinoma. [Abstract] Int J Radiat Oncol Biol Phys 63 (2 Suppl 1): A-116, S70, 2005.

Hammond E, Berkey BA, Fu KK, et al.: P105 as a prognostic indicator in patients irradiated for locally advanced head-and-neck cancer: a clinical/laboratory correlative analysis of RTOG-9003. Int J Radiat Oncol Biol Phys 57 (3): 683-92, 2003.[PUBMED Abstract]

Konski A, Berkey BA, Kian Ang K, et al.: Effect of education level on outcome of patients treated on Radiation Therapy Oncology Group Protocol 90-03. Cancer 98 (7): 1497-503, 2003.[PUBMED Abstract]

Tu X, Berkey BA, Zhang HZ, et al.: Impact of EGFR expression on the response of advanced head and neck carcinomas to concomitant boost radiotherapy in a RTOG phase III trial (90-03). Int J Radiat Oncol Biol Phys 57 (2 Suppl): S157, 2003.

Ang KK, Berkey BA, Tu X, et al.: Impact of epidermal growth factor receptor expression on survival and pattern of relapse in patients with advanced head and neck carcinoma. Cancer Res 62 (24): 7350-6, 2002.[PUBMED Abstract]

Eldridge B, Rabinovitch R, Berkey BA, et al.: The impact of baseline nutritional support on treatment outcome in patients with locally advanced squamous cell cancer of the head and neck treated with definitive radiotherapy: report of the Radiation Therapy Oncology Group (RTOG) trial 90-03. [Abstract] Int J Radiat Oncol Biol Phys 54(2 suppl 1): A-199, 115, 2002.

Konski A, Berkey B, Ang KK, et al.: The effect of education level on outcome of patients treated on Radiation Therapy Oncology Group (RTOG) protocol 90-03. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-992, 2002.

Calvin DP, Hammond ME, Pajak TF, et al.: Microvessel density (MVD)> 60 does not predict for outcome in advanced head and neck squamous cell carcinoma (HNSCC): results of a prospective study from the RTOG 90-03 trial. [Abstract] Int J Radiat Oncol Biol Phys 51 (3 suppl 1): A-68, 41, 2001.

Fisher J, Scott C, Fu K, et al.: Treatment, patient and tumor characteristics impact quality of life (QOL) in patients with locally advanced head and neck cancer: report of the Radiation Therapy Oncology Group (RTOG) trial 90-03. [Abstract] Int J Radiat Oncol Biol Phys 51 (3 suppl 1): A-174, 98, 2001.

Konski AA, Scott CB, Ang KK, et al.: Does dose escalation of radiotherapy (RT) improve quality-adjusted survival (QAS) in unresectable head and neck cancer (HNC) patients (Pts)? Radiation Therapy Oncology Group (RTOG) study 90-03. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-906, 227a, 2001.

Konski A, Scott C, Ang KK, et al.: Cost-utility analysis of RTOG 90-03: phase III randomized study comparing altered fractionation to standard fractionation radiotherapy for locally advanced head and neck squamous cell carcinoma. [Abstract] Int J Radiat Oncol Biol Phys 51(3 suppl 1): A-87, 48, 2001.

Fisher J, Scott C, Fu K, et al.: Randomized study comparing quality of life between standard fractionation radiotherapy and altered fractionation schemas in patients with locally advanced squamous cell cancer of the head and neck. [Abstract] Proceedings of the International Conference on Head and Neck Cancer A201, 117, 2000.

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 (1): 7-16, 2000.[PUBMED Abstract]

Hammond E, Pajak T, Fu K, et al.: p105 as a prognostic indicator in patients irradiated for locally advanced head and neck cancer: a clinical/laboratory correlative analysis of RTOG 9003. [Abstract] Proceedings of the International Conference on Head and Neck Cancer A135, 145, 2000.

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 radiography for head and neck squamous cell carcinomas: preliminary results of RTOG 9003. [Abstract] Int J Radiat Oncol Biol Phys 45 (3 suppl): A-1, 145, 1999.

Coyne JC, Pajak TF, Bruner DW: Reply to emotional well-being does not predict survival in head and neck cancer patients: a Radiation Therapy Oncology Group study. Cancer 112 (10): 2327-8, 2008.

Cullen KJ, Nikitakis N, Goloubeva O, et al.: Effect of elevated expression of GST-π and p53 on prognosis in head and neck cancer patients treated with chemoradiotherapy but not radiotherapy alone: An analysis of RTOG trials 9003 and 9501. [Abstract] J Clin Oncol 26 (Suppl 15): A-6013, 2008.

Schumaker L, Nikitakis N, Goloubeva O, et al.: Elevated expression of glutathione S-transferase pi and p53 confers poor prognosis in head and neck cancer patients treated with chemoradiotherapy but not radiotherapy alone. Clin Cancer Res 14 (18): 5877-83, 2008.[PUBMED Abstract]

Siddiqui F, Pajak TF, Watkins-Bruner D, et al.: Pretreatment quality of life predicts for locoregional control in head and neck cancer patients: a radiation therapy oncology group analysis. Int J Radiat Oncol Biol Phys 70 (2): 353-60, 2008.[PUBMED Abstract]

Spiegel D, Kraemer HC: Emotional well-being does not predict survival in head and neck cancer patients: a Radiation Therapy Oncology Group study. Cancer 112 (10): 2326-7; author reply 2327-8, 2008.[PUBMED Abstract]

Coyne JC, Pajak TF, Harris J, et al.: Emotional well-being does not predict survival in head and neck cancer patients: a Radiation Therapy Oncology Group study. Cancer 110 (11): 2568-75, 2007.[PUBMED Abstract]

Sanabria A, Carvalho AL, Kowalski LP: Is nutrition support related to a poor prognosis in head and neck cancer patients? Thoughts about the secondary analysis of RTOG trial 90-03. Head Neck 29 (5): 518-9; author reply 519-20, 2007.[PUBMED Abstract]

Konski AA, Pajak T, Movsas B, et al.: Socio-demographic variables influence outcome in Radiation Therapy Oncology Group head and neck trials. [Abstract] Proceedings of the American Society of Clinical Oncology 22 (Suppl 14): A-6043, 529s, 2004.

Kumar P, Harris J, Garden AS, et al.: Outcome comparisons of four Radiation Therapy Oncology Group (RTOG) trials in patients with stage IV-T4 head and neck (H/N) cancer: encouraging results using intra-arterial (IA) cisplatin (P) and concurrent radiation therapy (RT). [Abstract] J Clin Oncol 22 (Suppl 14): A-5527, 494s, 2004.

Movsas B, Konski A, Pajak T, et al.: Quality of life (QOL) variables influence local regional control in Radiation Therapy Oncology Group (RTOG) headsneck trials (9003 and 9111). [Abstract] Int J Radiat Oncol Biol Phys 60 (1 Suppl 1): A-199, S252, 2004.

Owen JB, Grigsby PW, Caldwell TM, et al.: Can costs be measured and predicted by modeling within a cooperative clinical trials group? Economic methodologic pilot studies of the radiation therapy oncology group (RTOG) studies 90-03 and 91-04. Int J Radiat Oncol Biol Phys 49 (3): 633-9, 2001.[PUBMED Abstract]

Owen J, Grigsby P, Caldwell T, et al.: Can costs be measured and predicted by modelling within a cooperative clinical trials group? Economic methodological pilot studies of Radiation Therapy Oncology Group studies 9003 and 9104. [Abstract] Int J Radiat Oncol Biol Phys 45 (3 suppl): A-150, 225, 1999.

Trial Contact Information

Trial Lead Organizations

Radiation Therapy Oncology Group

K. Kian Ang, MD, PhD, Protocol chair		Ph: 713-563-2300; 800-392-1611

Registry Information
Official Title		Phase III Randomized Comparison of Radiotherapy Fractionation in Advanced Squamous Cell Carcinoma of the Head and Neck: Twice-Daily Hyperfractionation vs Split-Course Accelerated Hyperfractionation vs Accelerated Fractionation with Concomitant Boost vs Standard Fractionation
Registered in ClinicalTrials.gov		NCT00771641
Date Submitted to PDQ		1991-09-30
Information Last Verified		2009-01-08
NCI Grant/Contract Number		CA31946