1.Hypofractionation versus conventional fractionation

• Population, Intervention, Comparator

  Population:

  Women with early breast cancer who had undergone breast conserving surgery; where reported, 0.15% had ductal carcinoma in situ and all had negative pathological margins. 91% of tumors were ≤ 3 cm. 39% of women receiving hypofractionation and 35% receiving conventional fractionation also received a radiation boost (an extra dose delivered to the tumor bed). 74% of women received tamoxifen and 21%, chemotherapy

  Intervention:

  Hypofractionation regimens varied across trials: from 28.5 Gy to 42.9 Gy in 5 to 16 fractions over 3 to 5 weeks where reported

  Comparator:

  Conventional fractionation: 50 Gy in 25 fractions over 5 weeks

• OUTCOME 1.1: Local recurrence-free survival

  Narrative result:

  This outcome was reported at different time points and no evidence of a difference between groups was seen at any time. Subgroup analysis by dose found similar results to the main analysis, although some of the analyses may have been underpowered. Click below for full details.

  Reference:

  Hickey BE, James ML, Lehman M, Hider PN, Jeffery M, Francis DP, See AM. Fraction size in radiation therapy for breast conservation in early breast cancer. Cochrane Database of Systematic Reviews 2016, Issue 7. Art. No.: CD003860. DOI: 10.1002/14651858.CD003860.pub4. [Review search date: May 2015]

  • Subgroup analysis 1.1.1: Local recurrence-free survival - [subgroup: LR-FS at median 3.5 years’ follow-up]

    Risk of bias of studies:

    The reviewers did not perform a GRADE assessment of the quality of the evidence. Of the two studies, one failed to report adequate allocation concealment and random sequence generation, did not report adequate blinding of participants/carers/outcome assessors and both had unclear numbers of withdrawals.

    Narrative result:

    Two RCTs with 955 participants found no statistically significant difference between groups.

    Relative effect or mean difference:

    There was no statistically significant difference between groups (HR 0.18, 95% CI 0.03 to 1.13).

    Forest plot from Cochrane Review

    Reference:

    Hickey BE, James ML, Lehman M, Hider PN, Jeffery M, Francis DP, See AM. Fraction size in radiation therapy for breast conservation in early breast cancer. Cochrane Database of Systematic Reviews 2016, Issue 7. Art. No.: CD003860. DOI: 10.1002/14651858.CD003860.pub4. [Review search date: May 2015]

  • Subgroup analysis 1.1.2: Local recurrence-free survival - [subgroup: LR-FS at median 10 years’ follow-up]

    Quality of the evidence:

    The reviewers performed a GRADE assessment of the quality of evidence for this outcome at this time point and stated that the evidence was high quality. See Summary of findings from Cochrane review

    Narrative result:

    Four RCTs with 7095 participants found no statistically significant difference between groups.

    Relative effect or mean difference:

    There was no statistically significant difference between groups (HR 0.94, 95% CI 0.77 to 1.15).

    Forest plot from Cochrane Review

    Absolute effect:

    66 per 1000 women (95% CI 54 to 80) with hypofractionation compared with 70 per 1000 women with conventional.

    Reference:

    Hickey BE, James ML, Lehman M, Hider PN, Jeffery M, Francis DP, See AM. Fraction size in radiation therapy for breast conservation in early breast cancer. Cochrane Database of Systematic Reviews 2016, Issue 7. Art. No.: CD003860. DOI: 10.1002/14651858.CD003860.pub4. [Review search date: May 2015]

• OUTCOME 1.2: Cosmesis (follow-up 42 months to 12 years)

  Quality of the evidence:

  The reviewers performed a GRADE assessment of the quality of evidence for this outcome at this time point and stated that the evidence was high quality. See Summary of findings from Cochrane review

  Narrative result:

  Four RCTs with 2103 participants found no statistically significant difference between groups. This outcome was assessed with a 4-point scale and the results were dichotomized as good or excellent versus poor or fair.

  Relative effect or mean difference:

  There was no statistically significant difference between groups (RR 0.90, 95% CI 0.81 to 1.01).

  Forest plot from Cochrane Review

  Absolute effect:

  280 per 1000 women (95% CI 252 to 314) with hypofractionation compared with 311 per 1000 women with conventional.

  Reference:

  Hickey BE, James ML, Lehman M, Hider PN, Jeffery M, Francis DP, See AM. Fraction size in radiation therapy for breast conservation in early breast cancer. Cochrane Database of Systematic Reviews 2016, Issue 7. Art. No.: CD003860. DOI: 10.1002/14651858.CD003860.pub4. [Review search date: May 2015]

• OUTCOME 1.3: Overall survival at 10 years’ median follow-up

  Quality of the evidence:

  The reviewers performed a GRADE assessment of the quality of evidence for this outcome at this time point and stated that the evidence was high quality. See Summary of findings from Cochrane review

  Narrative result:

  Three RCTs with 5685 participants found no statistically significant difference between groups.

  Relative effect or mean difference:

  There was no statistically significant difference between groups (HR 0.91, 95% CI 0.80 to 1.03).

  Forest plot from Cochrane Review

  Absolute effect:

  153 per 1000 women (95% CI 135 to 171) with hypofractionation compared with 166 per 1000 women with conventional.

  Reference:

  Hickey BE, James ML, Lehman M, Hider PN, Jeffery M, Francis DP, See AM. Fraction size in radiation therapy for breast conservation in early breast cancer. Cochrane Database of Systematic Reviews 2016, Issue 7. Art. No.: CD003860. DOI: 10.1002/14651858.CD003860.pub4. [Review search date: May 2015]

• OUTCOME 1.4: Acute skin radiation toxicity

  Risk of bias of studies:

  The reviewers did not perform a GRADE assessment of the quality of evidence for this outcome. Of the two studies, one failed to report adequate allocation concealment and random sequence generation, both reported adequate blinding of participants/carers/outcome assessors but had unclear numbers of withdrawals.

  Narrative result:

  Two RCTs with 357 participants found that fewer women had acute skin radiation toxicity with hypofractionation compared with conventional.

  Relative effect or mean difference:

  There was a statistically significant difference between groups, in favor of hypofractionation (RR 0.32, 95% CI 0.22 to 0.45).

  Forest plot from Cochrane Review

  Absolute effect:

  146 per 1000 women (95% CI 102 to 208) with hypofractionation compared with 464 per 1000 women with conventional.

  Reference:

  Hickey BE, James ML, Lehman M, Hider PN, Jeffery M, Francis DP, See AM. Fraction size in radiation therapy for breast conservation in early breast cancer. Cochrane Database of Systematic Reviews 2016, Issue 7. Art. No.: CD003860. DOI: 10.1002/14651858.CD003860.pub4. [Review search date: May 2015]

• OUTCOME 1.5: Late subcutaneous toxicity (fibrosis) (median follow-up 6 years)

  Quality of the evidence:

  The reviewers performed a GRADE assessment of the quality of evidence for this outcome at this time point and stated that the evidence was high quality. See Summary of findings from Cochrane review

  Narrative result:

  Four RCTs with 5130 participants found no statistically significant difference between groups. Subgroup analysis by time point (5 or 10 years) found similar results to the main analysis.

  Relative effect or mean difference:

  There was no statistically significant difference between groups (RR 0.93, 95% CI 0.83 to 1.05).

  Forest plot from Cochrane Review

  Absolute effect:

  4 per 1000 women (95% CI 3 to 4) with hypofractionation compared with 4 per 1000 women with conventional.

  Reference:

  Hickey BE, James ML, Lehman M, Hider PN, Jeffery M, Francis DP, See AM. Fraction size in radiation therapy for breast conservation in early breast cancer. Cochrane Database of Systematic Reviews 2016, Issue 7. Art. No.: CD003860. DOI: 10.1002/14651858.CD003860.pub4. [Review search date: May 2015]

• OUTCOME 1.6: Breast cancer-specific survival at 10 years

  Quality of the evidence:

  The reviewers performed a GRADE assessment of the quality of evidence for this outcome at this time point and stated that the evidence was high quality. See Summary of findings from Cochrane review

  Narrative result:

  Three RCTs with 5685 participants found no statistically significant difference between groups.

  Relative effect or mean difference:

  There was no statistically significant difference between groups (HR 0.91, 95% CI 0.78 to 1.06).

  Forest plot from Cochrane Review

  Absolute effect:

  113 per 1000 women (95% CI 98 to 130) with hypofractionation compared with 123 per 1000 women with conventional.

  Reference:

  Hickey BE, James ML, Lehman M, Hider PN, Jeffery M, Francis DP, See AM. Fraction size in radiation therapy for breast conservation in early breast cancer. Cochrane Database of Systematic Reviews 2016, Issue 7. Art. No.: CD003860. DOI: 10.1002/14651858.CD003860.pub4. [Review search date: May 2015]

• OUTCOME 1.7: Relapse-free survival

  Quality of the evidence:

  The reviewers performed a GRADE assessment of the quality of evidence for this outcome at this time point and stated that the evidence was moderate quality. See Summary of findings from Cochrane review

  Narrative result:

  Three RCTs with 5685 participants found no statistically significant difference between groups. Subgroup analysis by time point (5 or 10 years) found similar results to the main analysis.

  Relative effect or mean difference:

  There was no statistically significant difference between groups (HR 0.93, 95% CI 0.82 to 1.05).

  Forest plot from Cochrane Review

  Absolute effect:

  210 per 1000 women (95% CI 188 to 234) with hypofractionation compared with 224 per 1000 women with conventional.

  Reference:

  Hickey BE, James ML, Lehman M, Hider PN, Jeffery M, Francis DP, See AM. Fraction size in radiation therapy for breast conservation in early breast cancer. Cochrane Database of Systematic Reviews 2016, Issue 7. Art. No.: CD003860. DOI: 10.1002/14651858.CD003860.pub4. [Review search date: May 2015]

• OUTCOME 1.8: Quality of life

  Risk of bias of studies:

  The reviewers did not perform a GRADE assessment of the quality of the evidence. The study failed to report adequate allocation concealment but reported adequate blinding of participants/carers/outcome assessors and had low numbers of withdrawals.

  Narrative result:

  One RCT with 270 women reported this outcome. Fewer women treated with altered fraction size experienced fatigue (patient and physician-reported) compared with conventional fractionation at six months. No obvious difference between groups was seen for physical well-being, functional well-being, emotional well-being, social well-being and breast cancer concerns using FACT-B and FACT-G.

  Relative effect or mean difference:

  Data were reported narratively.

  Reference:

  Hickey BE, James ML, Lehman M, Hider PN, Jeffery M, Francis DP, See AM. Fraction size in radiation therapy for breast conservation in early breast cancer. Cochrane Database of Systematic Reviews 2016, Issue 7. Art. No.: CD003860. DOI: 10.1002/14651858.CD003860.pub4. [Review search date: May 2015]

• OUTCOME 1.9: Rate of mastectomy

  Narrative result:

  The reviewers found no studies assessing this outcome.

  Reference:

  Hickey BE, James ML, Lehman M, Hider PN, Jeffery M, Francis DP, See AM. Fraction size in radiation therapy for breast conservation in early breast cancer. Cochrane Database of Systematic Reviews 2016, Issue 7. Art. No.: CD003860. DOI: 10.1002/14651858.CD003860.pub4. [Review search date: May 2015]