Cochrane · intervention · CD006387
Interventions for the treatment of oral cavity and oropharyngeal cancer: radiotherapy
Glenny, AM, Furness, S, Worthington, HV, et al. · Cochrane Database of Systematic Reviews · 2010 · Cochrane Library
Full textEvery question was extracted from the full review (methods and results), not only its Summary of Findings table.
Questions
47
current version
GRADE rated
2
No studies
3
Included studies
30
as reported
No studies 3 · 6.4%Ungraded 42 · 89.4%Very low 1 · 2.1%Low 0 · 0%Moderate 1 · 2.1%High 0 · 0%
Ungraded means an effect was reported without a GRADE rating; it is not a gap. No studies means the review found nothing to answer the question. The six categories are a display order, not a score.
Review question
| Element | Planned (methods) | Found (results) |
|---|---|---|
| Population | Patients with cancer of the oral cavity (ICD-O C01-C06) or oropharynx (ICD-O C09-C10); primary squamous cell carcinoma of the oral mucosa; histological variants and carcinoma in situ included; head and neck cancer trials eligible if at least 50% of participants had oral cavity or oropharyngeal cancer (or separate data available) | Oral cavity or oropharyngeal cancer (at least 50% of participants in most trials); 2 trials oral cavity only, 4 oropharynx only, 1 either; recruitment periods 1 to 10 years from 1969; stages I-IV to III-IV |
| Intervention | Radiotherapy: any mode of administration, dose of fractionation and total dose, number of fractions per day and per week, and duration; the intervention under evaluation must be radiotherapy | Hyperfractionated (n=3); Hyperfractionated/accelerated (n=4); Hyperfractionated/accelerated/split (n=4); Accelerated (n=2); Accelerated/boost (n=4); Accelerated/split (n=1); Hyperfractionated/accelerated split course (n=1); Split course (n=1); Variable total dose (n=1); Mixed beam (n=1); Neutron (n=4); Pre-operative (n=3); Pre-operative and post-operative (n=1); Morning radiotherapy (n=1); Low dose rate interstitial (n=1) |
| Comparison | Alternative radiotherapy regimen; other treatment modality (surgery, chemotherapy); or the addition of radiotherapy to other treatment modalities | Conventional radiotherapy; Conventional photon radiotherapy; Surgery alone; Post-operative radiotherapy alone; Afternoon radiotherapy; High dose rate interstitial radiotherapy; Accelerated radiotherapy (comparator in Fu 1995 and Hukku 1991); Standard/conventional total dose (Cox 1990) |
| Outcomes | Primary: Overall survival/total mortality; Locoregional control; Disease free survival; Progression free survival or time to recurrence. Secondary: Quality of life; Harms associated with treatment; Direct and indirect costs to patients and health services; Patient satisfaction | Total mortality (n=21); Locoregional control (n=15); Disease free survival (n=8); Quality of life (n=1); Harms/adverse events (multiple trials); Direct and indirect costs (n=0); Patient satisfaction (n=0) |
| Study designs | Randomised controlled trials comparing radiotherapy with an alternative radiotherapy regimen or other treatment modality, or evaluating the addition of radiotherapy to other treatment modalities; minimum follow-up of 6 months | Randomised controlled trials (n=30) |
| Timing | Minimum follow-up of 6 months | Follow-up and recruitment 1 to 10 years (earliest recruitment 1969); mortality assessed around 5 years |
Search date: 2010-07. Databases: Cochrane Oral Health Group's Trials Register; Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE via OVID; EMBASE via OVID; Current Controlled Trials (www.controlled-trials.com)
Questions and results
Show all 2 versionsAltered fractionation radiotherapy (hyperfractionated and/or accelerated) vs Conventional (standard) fractionation radiotherapy
Population: People with primary squamous cell carcinoma of the oral cavity (ICD-O C01-C06) or oropharynx (ICD-O C09-C10); head and neck cancer trials eligible where more than 50% of participants had oral cavity or oropharyngeal cancer (or separate data available)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Mortality 5 years · All included studies | HR 0.86 [0.76, 0.98] Conventional: Low-risk 200 per 1000; Medium-risk 500 per 1000; High-risk 700 per 1000 vs Altered fractionation:… | 13 studies · 3751 participants | Very low Downgraded: risk of bias, inconsistency, indirectness |
Disease free survival | HR 0.85 [0.70, 1.03] | 8 studies | Ungraded |
Mortality 5 years · Studies at low risk of bias (sensitivity analysis) | HR 0.93 [0.80, 1.07] Conventional: Low-risk 200 per 1000; Medium-risk 500 per 1000; High-risk 700 per 1000 vs Altered fractionation:… | 5 studies · 1511 participants | Moderate Downgraded: indirectness |
Locoregional control | HR 0.79 [0.70, 0.89] | 11 studies | Ungraded |
Hyperfractionated radiotherapy vs Conventional (standard) fractionation radiotherapy
Population: People with primary squamous cell carcinoma of the oral cavity (ICD-O C01-C06) or oropharynx (ICD-O C09-C10); head and neck cancer trials eligible where more than 50% of participants had oral cavity or oropharyngeal cancer (or separate data available)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total mortality | HR 0.78 [0.68, 0.90] | 3 studies · 966 participants | Ungraded |
Locoregional control | HR 0.74 [0.62, 0.89] | 3 studies · 966 participants | Ungraded |
Disease free survival | Hyperfractionated vs conventional, disease free survival: data available for one trial (Fu 2000); no statistically significant difference (Analysis 1.3). No pooled estimate reported. | 1 study | Ungraded |
Hyperfractionated/accelerated radiotherapy vs Conventional (standard) fractionation radiotherapy
Population: People with primary squamous cell carcinoma of the oral cavity (ICD-O C01-C06) or oropharynx (ICD-O C09-C10); head and neck cancer trials eligible where more than 50% of participants had oral cavity or oropharyngeal cancer (or separate data available)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Locoregional control | HR 0.84 [0.72, 0.99] | 4 studies · 1071 participants | Ungraded |
Disease free survival | Hyperfractionated/accelerated vs conventional, disease free survival: one trial (Poulsen 2001); no statistically significant difference (Analysis 1.3). No pooled estimate. | 1 study | Ungraded |
Total mortality | HR 0.87 [0.75, 1.00] | 4 studies · 1071 participants | Ungraded |
Hyperfractionated/accelerated/split-course radiotherapy vs Conventional (standard) fractionation radiotherapy
Population: People with primary squamous cell carcinoma of the oral cavity (ICD-O C01-C06) or oropharynx (ICD-O C09-C10); head and neck cancer trials eligible where more than 50% of participants had oral cavity or oropharyngeal cancer (or separate data available)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Disease free survival | Hyperfractionated/accelerated/split vs conventional, disease free survival: two trials (Fu 2000, Olmi 2003); results contradictory with substantial statistical heterogeneity (P = 0.02, I2 = 82%); no pooled estimate… | 2 studies | Ungraded |
Total mortality | HR 1.02 [0.90, 1.17] | 4 studies · 1299 participants | Ungraded |
Locoregional control | HR 0.86 [0.74, 1.01] | 4 studies · 1299 participants | Ungraded |
Accelerated radiotherapy (no split, boost or hyperfractionation) vs Conventional (standard) fractionation radiotherapy
Population: People with primary squamous cell carcinoma of the oral cavity (ICD-O C01-C06) or oropharynx (ICD-O C09-C10); head and neck cancer trials eligible where more than 50% of participants had oral cavity or oropharyngeal cancer (or separate data available)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total mortality | Accelerated vs conventional, total mortality: only one trial reported data (Skladowski 2006; IPD available). A statistically significant difference in favour of the altered fractionation was shown (Analysis 1.1). No… | 1 study | Ungraded |
Locoregional control | Accelerated vs conventional, locoregional control: one trial (Skladowski 2006); a statistically significant difference in favour of the altered fractionation was shown (Analysis 1.2). No numeric estimate given. | 1 study | Ungraded |
Disease free survival | Accelerated vs conventional, disease free survival: both trials reported this, but substantial clinical and statistical heterogeneity (P = 0.0004, I2 = 92%) meant a pooled analysis was not reported (Analysis 1.3). | 2 studies | Ungraded |
Accelerated radiotherapy with concomitant boost vs Conventional (standard) fractionation radiotherapy
Population: People with primary squamous cell carcinoma of the oral cavity (ICD-O C01-C06) or oropharynx (ICD-O C09-C10); head and neck cancer trials eligible where more than 50% of participants had oral cavity or oropharyngeal cancer (or separate data available)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Disease free survival | Accelerated/boost vs conventional, disease free survival: all four trials provided data; pooled estimate showed a statistically significant difference in favour of the accelerated/boost schedule, with statistical… | 4 studies · 1203 participants | Ungraded |
Total mortality | HR 0.95 [0.80, 1.13] | 3 studies · 1203 participants | Ungraded |
Locoregional control | Accelerated/boost vs conventional, locoregional control: IPD from one trial (Fu 2000); a statistically significant difference in favour of the accelerated schedule with boost was shown (Analysis 1.2). No numeric… | 1 study | Ungraded |
Accelerated/split-course radiotherapy vs Conventional (standard) fractionation radiotherapy
Population: People with primary squamous cell carcinoma of the oral cavity (ICD-O C01-C06) or oropharynx (ICD-O C09-C10); head and neck cancer trials eligible where more than 50% of participants had oral cavity or oropharyngeal cancer (or separate data available)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total mortality 5 years | RR 1.17 [0.57, 2.43] | 1 study · 147 participants | Ungraded |
Hyperfractionated/accelerated split-course radiotherapy vs Accelerated radiotherapy with concomitant boost
Population: People with primary squamous cell carcinoma of the oral cavity (ICD-O C01-C06) or oropharynx (ICD-O C09-C10); head and neck cancer trials eligible where more than 50% of participants had oral cavity or oropharyngeal cancer (or separate data available)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total mortality | Hyperfractionated/accelerated split course vs accelerated boost (Fu 1995, feasibility study, 75 participants): authors report no significant difference in total mortality; data not presented in a way that allows… | 1 study · 75 participants | Ungraded |
Locoregional control | Fu 1995: no significant difference in locoregional control; data not presented in a way that allows calculation of an HR. | 1 study · 75 participants | Ungraded |
Disease free survival | Fu 1995: no significant difference in disease free survival; data not presented in a way that allows calculation of an HR. | 1 study · 75 participants | Ungraded |
Split-course radiotherapy vs Accelerated radiotherapy
Population: People with primary squamous cell carcinoma of the oral cavity (ICD-O C01-C06) or oropharynx (ICD-O C09-C10); head and neck cancer trials eligible where more than 50% of participants had oral cavity or oropharyngeal cancer (or separate data available)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Locoregional control 2 years | RR 1.33 [0.67, 2.67] | 1 study · 110 participants | Ungraded |
Total mortality 2 years | RR 1.00 [0.82, 1.22] | 1 study · 110 participants | Ungraded |
Disease free survival 2 years | RR 0.83 [0.29, 2.42] | 1 study · 110 participants | Ungraded |
Higher total dose radiotherapy (76.8 Gy over 6.4 weeks) vs Conventional/standard total dose radiotherapy (72 Gy)
Population: People with primary squamous cell carcinoma of the oral cavity (ICD-O C01-C06) or oropharynx (ICD-O C09-C10); head and neck cancer trials eligible where more than 50% of participants had oral cavity or oropharyngeal cancer (or separate data available)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total mortality | HR 1.08 [0.69, 1.70] | 1 study | Ungraded |
Locoregional control | HR 0.78 [0.55, 1.11] | 1 study | Ungraded |
Lower total dose radiotherapy (67.2 Gy over 5.6 weeks) vs Conventional/standard total dose radiotherapy (72 Gy)
Population: People with primary squamous cell carcinoma of the oral cavity (ICD-O C01-C06) or oropharynx (ICD-O C09-C10); head and neck cancer trials eligible where more than 50% of participants had oral cavity or oropharyngeal cancer (or separate data available)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Locoregional control | HR 1.13 [0.78, 1.64] | 1 study | Ungraded |
Total mortality | HR 1.38 [0.83, 2.29] | 1 study | Ungraded |
Mixed beam (neutron and photon) radiotherapy vs Conventional photon radiotherapy
Population: People with primary squamous cell carcinoma of the oral cavity (ICD-O C01-C06) or oropharynx (ICD-O C09-C10); head and neck cancer trials eligible where more than 50% of participants had oral cavity or oropharyngeal cancer (or separate data available)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Locoregional control | HR 1.04 [0.84, 1.29] | 1 study · 327 participants | Ungraded |
Total mortality | HR 1.12 [0.92, 1.36] | 1 study · 327 participants | Ungraded |
Neutron radiotherapy vs Conventional photon radiotherapy
Population: People with primary squamous cell carcinoma of the oral cavity (ICD-O C01-C06) or oropharynx (ICD-O C09-C10); head and neck cancer trials eligible where more than 50% of participants had oral cavity or oropharyngeal cancer (or separate data available)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Locoregional control 5 years | RR 0.97 [0.69, 1.36] | 1 study | Ungraded |
Total mortality | HR 1.10 [0.90, 1.34] | 3 studies | Ungraded |
Disease free survival 5 years | RR 0.63 [0.36, 1.09] | 1 study | Ungraded |
Pre-operative radiotherapy (plus surgery) vs Surgery alone
Population: People with primary squamous cell carcinoma of the oral cavity (ICD-O C01-C06) or oropharynx (ICD-O C09-C10); head and neck cancer trials eligible where more than 50% of participants had oral cavity or oropharyngeal cancer (or separate data available)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total mortality | HR 0.83 [0.64, 1.07] | 1 study | Ungraded |
Locoregional control Timing unclear | RR 0.63 [0.28, 1.46] | 1 study | Ungraded |
Pre-operative and post-operative radiotherapy vs Post-operative radiotherapy alone
Population: People with primary squamous cell carcinoma of the oral cavity (ICD-O C01-C06) or oropharynx (ICD-O C09-C10); head and neck cancer trials eligible where more than 50% of participants had oral cavity or oropharyngeal cancer (or separate data available)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Locoregional control | HR 1.13 [0.78, 1.64] | 1 study | Ungraded |
Disease free survival | HR 1.13 [0.78, 1.64] | 1 study | Ungraded |
Total mortality | HR 0.67 [0.35, 1.28] | 1 study | Ungraded |
Morning radiotherapy vs Afternoon radiotherapy
Population: People with primary squamous cell carcinoma of the oral cavity (ICD-O C01-C06) or oropharynx (ICD-O C09-C10); head and neck cancer trials eligible where more than 50% of participants had oral cavity or oropharyngeal cancer (or separate data available)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Total mortality 2 years | RR 1.09 [0.74, 1.59] | 1 study · 216 participants | Ungraded |
Quality of life | Bjarnason 2009: no statistically significant difference in quality of life scores (data not reported). Morning radiotherapy was associated with significantly less weight loss after 5 months. | 1 study · 216 participants | Ungraded |
Locoregional control | HR 0.92 [0.60, 1.42] | 1 study · 216 participants | Ungraded |
Low dose rate interstitial radiotherapy vs High dose rate interstitial radiotherapy
Population: People with primary squamous cell carcinoma of the oral cavity (ICD-O C01-C06) or oropharynx (ICD-O C09-C10); head and neck cancer trials eligible where more than 50% of participants had oral cavity or oropharyngeal cancer (or separate data available)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Locoregional control | HR 1.00 [0.16, 6.44] | 1 study · 59 participants | Ungraded |
Intensity modulated radiotherapy (IMRT) vs Conventional or other radiotherapy
Population: People with primary squamous cell carcinoma of the oral cavity (ICD-O C01-C06) or oropharynx (ICD-O C09-C10); head and neck cancer trials eligible where more than 50% of participants had oral cavity or oropharyngeal cancer (or separate data available)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcome NR | Discussion: 'There are currently no trials of IMRT in this systematic review' (the PARSPORT trial was underway, expected 2013). No eligible trials of intensity modulated radiotherapy identified. | 0 studies | No studies |
Altered fractionation radiotherapy vs Chemoradiotherapy (concurrent, standard fractionation)
Population: People with primary squamous cell carcinoma of the oral cavity (ICD-O C01-C06) or oropharynx (ICD-O C09-C10); head and neck cancer trials eligible where more than 50% of participants had oral cavity or oropharyngeal cancer (or separate data available)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcome NR | Discussion: altered fractionation radiotherapy 'has not been directly compared to chemoradiotherapy'. No eligible head-to-head trials. | 0 studies | No studies |
Altered fractionation radiotherapy plus chemotherapy vs Chemoradiotherapy with standard (conventional) fractionation
Population: People with primary squamous cell carcinoma of the oral cavity (ICD-O C01-C06) or oropharynx (ICD-O C09-C10); head and neck cancer trials eligible where more than 50% of participants had oral cavity or oropharyngeal cancer (or separate data available)
| Outcome | Effect | Evidence | Status / GRADE |
|---|---|---|---|
Outcome NR | Discussion: 'there are no completed trials of altered fractionation plus chemotherapy versus chemoradiotherapy with standard fractionation.' | 0 studies | No studies |