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Altered Fractionation Versus Standard Fractionation Radiation Therapy
Source: Laryngeal Cancer Treatment (PDQ®)–Health Professional Version, National Cancer Institute.
Source updated: May 14, 2025 · Captured 2026-09-09.
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Context: Treatment Option Overview for Laryngeal Cancer
Radiation therapy alone with altered fractionation may be used for patients with locally advanced laryngeal cancer who are not candidates for chemotherapy. Altered fractionation radiation therapy yields a higher locoregional control rate compared with standard fractionated radiation therapy for patients with stage III and stage IV head and neck cancer.
Evidence (altered fractionation vs. standard fractionation radiation therapy):
The randomized RTOG-9003 trial (NCT00771641) included four radiation therapy treatment arms:[21,22][Level of evidence A1]In a long-term analysis, the three investigational arms were compared with SFX.
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The randomized RTOG-9003 trial (NCT00771641) included four radiation therapy treatment arms:[21,22][Level of evidence A1]In a long-term analysis, the three investigational arms were compared with SFX.
Standard fractionation (SFX) to 70 Gy in 35 daily fractions for 7 weeks.
The randomized RTOG-9003 trial (NCT00771641) included four radiation therapy treatment arms:[21,22][Level of evidence A1]In a long-term analysis, the three investigational arms were compared with SFX.
Hyperfractionation (HFX) to 81.6 Gy in 68 twice-daily fractions for 7 weeks.
The randomized RTOG-9003 trial (NCT00771641) included four radiation therapy treatment arms:[21,22][Level of evidence A1]In a long-term analysis, the three investigational arms were compared with SFX.
Accelerated fractionation split course (AFX-S) to 67.2 Gy in 42 fractions for 6 weeks with a 2-week rest after 38.4 Gy.
The randomized RTOG-9003 trial (NCT00771641) included four radiation therapy treatment arms:[21,22][Level of evidence A1]In a long-term analysis, the three investigational arms were compared with SFX.
Accelerated concurrent boost fractionation (AFX-C) to 72 Gy in 42 fractions for 6 weeks.
The randomized RTOG-9003 trial (NCT00771641) included four radiation therapy treatment arms:[21,22][Level of evidence A1]In a long-term analysis, the three investigational arms were compared with SFX.
Only the HFX arm showed superior locoregional control and survival at 5 years compared with the SFX arm (HR, 0.79; 95% CI, 0.62–1.00; P = .05).
The randomized RTOG-9003 trial (NCT00771641) included four radiation therapy treatment arms:[21,22][Level of evidence A1]In a long-term analysis, the three investigational arms were compared with SFX.
AFX-C was associated with increased late toxicity compared with SFX.
The following results were shown in a meta-analysis of 15 randomized trials with a total of 6,515 patients and a median follow-up of 6 years involving the assessment of HFX or AFX-S for patients with stage III and stage IV oropharyngeal cancer:[23][Level of evidence A1]
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The following results were shown in a meta-analysis of 15 randomized trials with a total of 6,515 patients and a median follow-up of 6 years involving the assessment of HFX or AFX-S for patients with stage III and stage IV oropharyngeal cancer:[23][Level of evidence A1]
There was a significant survival benefit with altered-fractionated radiation therapy and a 3.4% absolute benefit at 5 years (HR, 0.92; 95% CI, 0.86–0.97; P = .003).
The following results were shown in a meta-analysis of 15 randomized trials with a total of 6,515 patients and a median follow-up of 6 years involving the assessment of HFX or AFX-S for patients with stage III and stage IV oropharyngeal cancer:[23][Level of evidence A1]
Altered-fractionation radiation therapy improves locoregional control, with greater benefit shown in younger patients.
The following results were shown in a meta-analysis of 15 randomized trials with a total of 6,515 patients and a median follow-up of 6 years involving the assessment of HFX or AFX-S for patients with stage III and stage IV oropharyngeal cancer:[23][Level of evidence A1]
HFX demonstrated a greater survival benefit (8% at 5 years) than did AFX-S (2% with accelerated fractionation without total dose-reduction and 1.7% with total dose-reduction at 5 years; P = .02).
An additional late effect from radiation therapy is hypothyroidism, which occurs in 30% to 40% of patients who have received external-beam radiation therapy to the entire thyroid gland. Thyroid function testing of patients is a consideration before therapy and as part of posttreatment follow-up.[24,25]
Prospective data from two randomized controlled trials reported the incidence of hypothyroidism.[26]
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At a median follow-up of 41 months, 55.1% of the patients developed hypothyroidism (39.3% subclinical, 15.7% biochemical).
Patients who underwent intensity-modulated radiation therapy (IMRT) had higher subclinical hypothyroidism (51.1% vs. 27.3%; P = .021), peaking around 1 year after radiation therapy.
Younger age, hypopharynx/larynx primary, node positivity, higher dose/fraction (IMRT arm), and D100 were statistically significant factors for developing hypothyroidism.[26][Level of evidence A3]
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For patients with well-lateralized oropharyngeal cancer, such as a T1 or T2 tonsil primary tumor with limited extension into the palate or tongue base and limited ipsilateral lymph node involvement without extracapsular extension, elective treatment to the ipsilateral lymph nodes results in only minimal risk of spread to the contralateral neck.[27] For T3 and T4 tumors that are midline or approach the midline, bilateral nodal treatment is a consideration. In addition to the cervical lymph node chain, retropharyngeal lymph nodes can also be encompassed in the elective nodal treatment.
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