Altered Fractionation

RTOG 9003 (Fu et al)

  • Stage III or IV oral cavity, oropharynx, and supraglottic larynx
  • Stage II – IV base of tongue or hypophaynx
  • 1073 patients
  • Median follow-up 23 months
  • No metastatic disease
2 year follow-up Conventional fractionation Hyper-fractionation Accelerated fractionation with split concomitant boost
Fractionation 2 Gy/fxn, total dose 70 Gy 1.2Gy/fxn BID to 81.6 Gy 1.6 Gy/fxn BID to 67.2 Gy
2 week break after 38.4 Gy
1.8 Gy/fxn daily for 6 weeks
1.5 Gy/fxn BID boost for last 12 treatments, total dose 72 Gy
Local Control 46.0% 54.4% 47.5% 54.5%
Disease-free survival 31.7% 37.6% 33.2% 39.3%
Overall survival 46.1% 54.5% 46.2% 50.9%


  • Hyperfractionation results in a 10 to 15% increase in tumor control due to an increase in total dose
  • Late morbidity is not increased
  • Extremely short treatment times with decreased total dose (CHART) did not translate into improved tumor control
  • Acute reactions are similar or slightly increased compared with conventional fractionation

Meta-analysis by MARCH

  • 3·4% overall survival benefit in favor of altered fractionation at 5 years
  • hyperfractionated radiotherapy (8% benefit at 5 years) better than with accelerated radiotherapy (2% benefit at 5 years). Also hyperfraction is the only group with both survival and local control benefit.
  • Reduced local failures (6·4% at 5 years; p<0·0001), benefit on nodal control was less pronounced.
  • youngest patients < 50 benefited most; no measurable benefit for > 70 year olds.
  • The magnitude of the benefit from hyperfractionation (8%) is similar to that of concurrent chemoradiation therapy (6.5%).

Time/Dose Consideration

  • continuous better than split in nasopharynx, oropharynx and larynx.[2],[4]
  • 5.9% increase in local recurrence per day of prolongation of treatment time for nasopharynx.[3]
1. Bourhis J, Overgaard J, Audry H, Ang KK, Saunders M, Bernier J, Horiot JC, Le Maître A, Pajak TF, Poulsen MG, O'Sullivan B, Dobrowsky W, Hliniak A, Skladowski K, Hay JH, Pinto LH, Fallai C, Fu KK, Sylvester R, Pignon JP; Meta-Analysis of Radiotherapy in Carcinomas of Head and neck (MARCH) Collaborative Group. Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis. Lancet. 2006 Sep 2;368(9538):843-54. Review.The Lancet 368
2. Luo R-X, et al: Comparison of continuous and split-course radiotherapy for nasopharyngeal carcinoma: An analysis of 1446 cases with squamous cell carcinoma grade 3. IJROBP 30: 1107-1109, 1994).
3. Lee AWM, Chan DKK, Fowler JF, et al. Effect of time, dose and fractionation on local control of nasopharyngeal carcinoma. Radiotherapy Oncology 36: 24-31, 1995.
4. Wang CC, et al. Local control of T3 carcinomas after accelerated fractionation: a look at the "gap" [Abstract]. IJROBP 32(suppl 1): 162, 1995.
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