Defining the expected 30-day mortality for patients undergoing palliative radiotherapy: A meta-analysis.

BACKGROUND: The expected 30-day mortality rate for patients treated with palliative radiationisnotestablished. The primary objective of this study is todefinetheproportion of patientswith advanced cancerwho diewithin 30-daysofpalliative radiotherapy(PR). Additionally, we explored the short term survival of patient subgroups undergoing PR treatment. METHODS: We searched MEDLINE, CINAHL, Embase and Cochrane Database of Systematic Reviews from January 1st 1980 to June 26, 2020. We included PUBMED's related search and reference lists to further identify articles. A meta-analysis of these research studies and reviews was performed. Published and unpublished English language randomized controlled trials, observational or prospective studies, and systematic reviews that reported 30-day mortality for patients with advanced cancer who received PR were eligible. Data extraction was done by two independent authors and included study quality indicators. To improve distribution and variance, all proportions were transformed using logit transformation. A random-effects model was used to pool data, using Der Simonian and Laird method of estimation where possible and appropriate. RESULTS: The data from 42 studies contributing 88,516 patients with advanced cancer who received PR were evaluated. The summary proportion of mortality in patients with advanced cancer within 30 days of receiving PR was 16% (95% CI = 14% to 18%). We found substantial heterogeneity in our data (I2 = 98.76%, p < 0.001), hence we applied subgroup analysis to identify potential moderating factors. We found a higher 30-day mortality rate after PR in the following groups: multiple treatment sites (QM(1) = 9.54, p = 0.002), hepatobiliary primary (QM(1) = 24.20, p < 0.001), inpatient status (QM(1) = 92.27, p < 0.001), Eastern Cooperative Oncology Group performance status (ECOG) 3-4 (QM(1) = 8.70, p = 0.003), United States (U.S.) patients (QM(1) = 28.70, p < 0.001) among others. CONCLUSIONS: We found that 16% of patients with advanced cancer receiving PR die within 30 days of treatment. Our findingcan be used asabenchmarktoestablishaglobal quality metric for radiation oncology practice audits.

Partial breast irradiation versus whole breast radiotherapy for early breast cancer.

BACKGROUND: Breast-conserving therapy for women with breast cancer consists of local excision of the tumour (achieving clear margins) followed by radiotherapy (RT). Most true recurrences occur in the same quadrant as the original tumour. Whole breast radiotherapy (WBRT) may not protect against the development of a new primary cancer developing in other quadrants of the breast. In this Cochrane Review, we investigated the delivery of radiation to a limited volume of the breast around the tumour bed (partial breast irradiation (PBI)) sometimes with a shortened treatment duration (accelerated partial breast irradiation (APBI)). OBJECTIVES: To determine whether PBI/APBI is equivalent to or better than conventional or hypofractionated WBRT after breast-conserving therapy for early-stage breast cancer. SEARCH METHODS: On 27 August 2020, we searched the Cochrane Breast Cancer Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and three trial databases. We searched for grey literature: OpenGrey (September 2020), reference lists of articles, conference proceedings and published abstracts, and applied no language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) without confounding, that evaluated conservative surgery plus PBI/APBI versus conservative surgery plus WBRT. Published and unpublished trials were eligible. DATA COLLECTION AND ANALYSIS: Two review authors (BH and ML) performed data extraction, used Cochrane's risk of bias tool and resolved any disagreements through discussion, and assessed the certainty of the evidence for main outcomes using GRADE. Main outcomes were local recurrence-free survival, cosmesis, overall survival, toxicity (subcutaneous fibrosis), cause-specific survival, distant metastasis-free survival and subsequent mastectomy. We entered data into Review Manager 5 for analysis. MAIN RESULTS: We included nine RCTs that enrolled 15,187 women who had invasive breast cancer or ductal carcinoma in-situ (6.3%) with T1-2N0-1M0 Grade I or II unifocal tumours (less than 2 cm or 3 cm or less) treated with breast-conserving therapy with negative margins. This is the second update of the review and includes two new studies and 4432 more participants. Local recurrence-free survival is probably slightly reduced (by 3/1000, 95% CI 6 fewer to 0 fewer) with the use of PBI/APBI compared to WBRT (hazard ratio (HR) 1.21, 95% confidence interval (CI) 1.03 to 1.42; 8 studies, 13,168 participants; moderate-certainty evidence). Cosmesis (physician/nurse-reported) is probably worse (by 63/1000, 95% CI 35 more to 92 more) with the use of PBI/APBI (odds ratio (OR) 1.57, 95% CI 1.31 to 1.87; 6 studies, 3652 participants; moderate-certainty evidence). Overall survival is similar (0/1000 fewer, 95% CI 6 fewer to 6 more) with PBI/APBI and WBRT (HR 0.99, 95% CI 0.88 to 1.12; 8 studies, 13,175 participants; high-certainty evidence). Late radiation toxicity (subcutaneous fibrosis) is probably increased (by 14/1000 more, 95% CI 102 more to 188 more) with PBI/APBI (OR 5.07, 95% CI 3.81 to 6.74; 2 studies, 3011 participants; moderate-certainty evidence). The use of PBI/APBI probably makes little difference (1/1000 less, 95% CI 6 fewer to 3 more) to cause-specific survival (HR 1.06, 95% CI 0.83 to 1.36; 7 studies, 9865 participants; moderate-certainty evidence). We found the use of PBI/APBI compared with WBRT probably makes little or no difference (1/1000 fewer (95% CI 4 fewer to 6 more)) to distant metastasis-free survival (HR 0.95, 95% CI 0.80 to 1.13; 7 studies, 11,033 participants; moderate-certainty evidence). We found the use of PBI/APBI in comparison with WBRT makes little or no difference (2/1000 fewer, 95% CI 20 fewer to 20 more) to mastectomy rates (OR 0.98, 95% CI 0.78 to 1.23; 3 studies, 3740 participants, high-certainty evidence). AUTHORS' CONCLUSIONS: It appeared that local recurrence-free survival is probably worse with PBI/APBI; however, the difference was small and nearly all women remain free of local recurrence. Overall survival is similar with PBI/APBI and WBRT, and we found little to no difference in other oncological outcomes. Some late effects (subcutaneous fibrosis) may be worse with PBI/APBI and its use is probably associated with worse cosmetic outcomes. The limitations of the data currently available mean that we cannot make definitive conclusions about the efficacy and safety or ways to deliver PBI/APBI. We await completion of ongoing trials.

Prognostic tools for survival prediction in advanced cancer patients: A systematic review.

Survival prediction for palliative cancer patients by physicians is often optimistic. Patients with a very short life expectancy (<4 weeks) may not benefit from radiation therapy (RT), as the time to maximal symptom relief after treatment can take 4-6 weeks. We aimed to identify a prognostic tool (or tools) to predict survival of less than 4 weeks and less than 3 months in patients with advanced cancer to guide the choice of radiation dose and fractionation. We searched Embase, Medline (EBSCOhost) and CINAHL (EBSCOhost) clinical databases for literature published between January 2008 and June 2018. Seventeen studies met the inclusion criteria and were included in the review. Prediction accuracy at less than 4 weeks and less than 3 months were compared across the prognostic tools. Reporting of prediction accuracy among the different studies was not consistent: the Palliative Prognostic Score (PaP), Palliative Prognostic Index (PPI) and Number of Risk Factors (NRF) best-predicted survival duration of less than 4 weeks. The PPI, performance status with Palliative Prognostic Index (PS-PPI), NRF and Survival Prediction Score (SPS) may predict 3-month survival. We recommend PPI and PaP tools to assess the likelihood of a patient surviving less than 4 weeks. If predicted to survive longer and RT is justified, the NRF tool could be used to determine survival probability less than 3 months which can then help clinicians select dose and fractionation. Future research is needed to verify the reliability of survival prediction using these prognostic tools in a radiation oncology setting.

Follow-up strategies for patients treated for non-metastatic colorectal cancer.

BACKGROUND: This is the fourth update of a Cochrane Review first published in 2002 and last updated in 2016.It is common clinical practice to follow patients with colorectal cancer for several years following their curative surgery or adjuvant therapy, or both. Despite this widespread practice, there is considerable controversy about how often patients should be seen, what tests should be performed, and whether these varying strategies have any significant impact on patient outcomes. OBJECTIVES: To assess the effect of follow-up programmes (follow-up versus no follow-up, follow-up strategies of varying intensity, and follow-up in different healthcare settings) on overall survival for patients with colorectal cancer treated with curative intent. Secondary objectives are to assess relapse-free survival, salvage surgery, interval recurrences, quality of life, and the harms and costs of surveillance and investigations. SEARCH METHODS: For this update, on 5 April 2109 we searched CENTRAL, MEDLINE, Embase, CINAHL, and Science Citation Index. We also searched reference lists of articles, and handsearched the Proceedings of the American Society for Radiation Oncology. In addition, we searched the following trials registries: ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. We contacted study authors. We applied no language or publication restrictions to the search strategies. SELECTION CRITERIA: We included only randomised controlled trials comparing different follow-up strategies for participants with non-metastatic colorectal cancer treated with curative intent. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently determined study eligibility, performed data extraction, and assessed risk of bias and methodological quality. We used GRADE to assess evidence quality. MAIN RESULTS: We identified 19 studies, which enrolled 13,216 participants (we included four new studies in this second update). Sixteen out of the 19 studies were eligible for quantitative synthesis. Although the studies varied in setting (general practitioner (GP)-led, nurse-led, or surgeon-led) and 'intensity' of follow-up, there was very little inconsistency in the results.Overall survival: we found intensive follow-up made little or no difference (hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.80 to 1.04: I² = 18%; high-quality evidence). There were 1453 deaths among 12,528 participants in 15 studies. In absolute terms, the average effect of intensive follow-up on overall survival was 24 fewer deaths per 1000 patients, but the true effect could lie between 60 fewer to 9 more per 1000 patients.Colorectal cancer-specific survival: we found intensive follow-up probably made little or no difference (HR 0.93, 95% CI 0.81 to 1.07: I² = 0%; moderate-quality evidence). There were 925 colorectal cancer deaths among 11,771 participants enrolled in 11 studies. In absolute terms, the average effect of intensive follow-up on colorectal cancer-specific survival was 15 fewer colorectal cancer-specific survival deaths per 1000 patients, but the true effect could lie between 47 fewer to 12 more per 1000 patients.Relapse-free survival: we found intensive follow-up made little or no difference (HR 1.05, 95% CI 0.92 to 1.21; I² = 41%; high-quality evidence). There were 2254 relapses among 8047 participants enrolled in 16 studies. The average effect of intensive follow-up on relapse-free survival was 17 more relapses per 1000 patients, but the true effect could lie between 30 fewer and 66 more per 1000 patients.Salvage surgery with curative intent: this was more frequent with intensive follow-up (risk ratio (RR) 1.98, 95% CI 1.53 to 2.56; I² = 31%; high-quality evidence). There were 457 episodes of salvage surgery in 5157 participants enrolled in 13 studies. In absolute terms, the effect of intensive follow-up on salvage surgery was 60 more episodes of salvage surgery per 1000 patients, but the true effect could lie between 33 to 96 more episodes per 1000 patients.Interval (symptomatic) recurrences: these were less frequent with intensive follow-up (RR 0.59, 95% CI 0.41 to 0.86; I² = 66%; moderate-quality evidence). There were 376 interval recurrences reported in 3933 participants enrolled in seven studies. Intensive follow-up was associated with fewer interval recurrences (52 fewer per 1000 patients); the true effect is between 18 and 75 fewer per 1000 patients.Intensive follow-up probably makes little or no difference to quality of life, anxiety, or depression (reported in 7 studies; moderate-quality evidence). The data were not available in a form that allowed analysis.Intensive follow-up may increase the complications (perforation or haemorrhage) from colonoscopies (OR 7.30, 95% CI 0.75 to 70.69; 1 study, 326 participants; very low-quality evidence). Two studies reported seven colonoscopic complications in 2292 colonoscopies, three perforations and four gastrointestinal haemorrhages requiring transfusion. We could not combine the data, as they were not reported by study arm in one study.The limited data on costs suggests that the cost of more intensive follow-up may be increased in comparison with less intense follow-up (low-quality evidence). The data were not available in a form that allowed analysis. AUTHORS' CONCLUSIONS: The results of our review suggest that there is no overall survival benefit for intensifying the follow-up of patients after curative surgery for colorectal cancer. Although more participants were treated with salvage surgery with curative intent in the intensive follow-up groups, this was not associated with improved survival. Harms related to intensive follow-up and salvage therapy were not well reported.

Hypofractionation for clinically localized prostate cancer.

BACKGROUND: Using hypofractionation (fewer, larger doses of daily radiation) to treat localized prostate cancer may improve convenience and resource use. For hypofractionation to be feasible, it must be at least as effective for cancer-related outcomes and have comparable toxicity and quality of life outcomes as conventionally fractionated radiation therapy. OBJECTIVES: To assess the effects of hypofractionated external beam radiation therapy compared to conventionally fractionated external beam radiation therapy for men with clinically localized prostate cancer. SEARCH METHODS: We searched CENTRAL, MEDLINE (Ovid), Embase (Ovid) and trials registries from 1946 to 15 March 2019 with reference checking, citation searching and contact with study authors. Searches were not limited by language or publication status. We reran all searches within three months (15th March 2019) prior to publication. SELECTION CRITERIA: Randomized controlled comparisons which included men with clinically localized prostate adenocarcinoma where hypofractionated radiation therapy (external beam radiation therapy) to the prostate using hypofractionation (greater than 2 Gy per fraction) compared with conventionally fractionated radiation therapy to the prostate delivered using standard fractionation (1.8 Gy to 2 Gy per fraction). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. Two authors independently assessed trial quality and extracted data. We used Review Manager 5 for data analysis and meta-analysis. We used the inverse variance method and random-effects model for data synthesis of time-to-event data with hazard ratios (HR) and 95% confidence intervals (CI) reported. For dichotomous data, we used the Mantel-Haenzel method and random-effects model to present risk ratios (RR) and 95% CI. We used GRADE to assess evidence quality for each outcome. MAIN RESULTS: We included 10 studies with 8278 men in our analysis comparing hypofractionation with conventional fractionation to treat prostate cancer.Primary outcomesHypofractionation may result in little or no difference in prostate cancer-specific survival [PC-SS] (HR 1.00, 95% CI 0.72 to 1.39; studies = 8, participants = 7946; median follow-up 72 months; low-certainty evidence). For men in the intermediate-risk group undergoing conventional fractionation this corresponds to 976 per 1000 men alive after 6 years and 0 more (44 fewer to 18 more) alive per 1000 men undergoing hypofractionation.We are uncertain about the effect of hypofractionation on late radiation therapy gastrointestinal (GI) toxicity (RR 1.10, 95% CI 0.68 to 1.78; studies = 4, participants = 3843; very low-certainty evidence).Hypofractionation probably results in little or no difference to late radiation therapy genitourinary (GU) toxicity (RR 1.05, 95% CI 0.93 to 1.18; studies = 4, participants = 3843; moderate-certainty evidence). This corresponds to 262 per 1000 late GU radiation therapy toxicity events with conventional fractionation and 13 more (18 fewer to 47 more) per 1000 men when undergoing hypofractionation.Secondary outcomesHypofractionation results in little or no difference in overall survival (HR 0.94, 95% CI 0.83 to 1.07; 10 studies, 8243 participants; high-certainty evidence). For men in the intermediate-risk group undergoing conventional fractionation this corresponds to 869 per 1000 men alive after 6 years and 17 fewer (54 fewer to 17 more) participants alive per 1000 men when undergoing hypofractionation.Hypofractionation may result in little to no difference in metastasis-free survival (HR 1.07, 95% CI 0.65 to 1.76; 5 studies, 4985 participants; low-certainty evidence). This corresponds to 981 men per 1000 men metastasis-free at 6 years when undergoing conventional fractionation and 5 more (58 fewer to 19 more) metastasis-free per 1000 when undergoing hypofractionation.Hypofractionation likely results in a small, possibly unimportant reduction in biochemical recurrence-free survival based on Phoenix criteria (HR 0.88, 95% CI 0.68 to 1.13; studies = 5, participants = 2889; median follow-up 90 months to 108 months; moderate-certainty evidence). In men of the intermediate-risk group, this corresponds to 804 biochemical-recurrence free men per 1000 participants at six years with conventional fractionation and 42 fewer (134 fewer to 37 more) recurrence-free men per 1000 participants with hypofractionationHypofractionation likely results in little to no difference to acute GU radiation therapy toxicity (RR 1.03, 95% CI 0.95 to 1.11; 4 studies, 4174 participants at 12 to 18 weeks' follow-up; moderate-certainty evidence). This corresponds to 360 episodes of toxicity per 1000 participants with conventional fractionation and 11 more (18 fewer to 40 more) per 1000 when undergoing hypofractionation. AUTHORS' CONCLUSIONS: These findings suggest that moderate hypofractionation (up to a fraction size of 3.4 Gy) results in similar oncologic outcomes in terms of disease-specific, metastasis-free and overall survival. There appears to be little to no increase in both acute and late toxicity.

Efficacy of flattening-filter-free beam in stereotactic body radiation therapy planning and treatment: A systematic review with meta-analysis.

A linear accelerator with the flattening-filter removed generates a non-uniform dose profile beam. We aimed to analyse and compare plan quality and treatment time between flattened beam (FB) and flattening-filter-free (FFF) beam to assess the efficacy of FFF beam for stereotactic body radiation therapy (SBRT). The search strategy was based around 3 concepts; radiation therapy, flattening-filter-free and treatment delivery. The years searched were restricted from 2010 to date of review (October 2015). All plan quality comparisons were between FFF and FB plans from the same data sets. We identified 210 potential studies based on the three searched concepts. All articles were screened by two authors for title and abstract and by three authors for full text. Ten studies met the eligibility criteria. Plan quality was evaluated using conformity index (CI), heterogeneity index (HI) and gradient index (GI). Dose to organs-at-risk (OAR) and healthy tissues were compared. Differences between beam-on-time (BOT) and treatment time (T × T) were also analysed. Normalized percentage ratios of CI and HI demonstrated no clinical differences among the studied articles. GI displayed small variations between the articles favouring FFF beam. The BOT with FFF is substantially reduced, and appears to impact the frequency of intra-fraction imaging which, in turn, affects total treatment time. Based on planning tumour volume (PTV) coverage, dose to OAR and healthy tissue sparing, FFF beam is clinically effective for the treatment of cancer patients using SBRT. We recommend the use of FFF beam for SBRT based on these factors and the reported overall treatment time reduction.

Intervention quality is not routinely assessed in Cochrane systematic reviews of radiation therapy interventions.

INTRODUCTION: The aim of this study was to maximise the benefits from clinical trials involving technological interventions such as radiation therapy. High compliance to the quality assurance protocols is crucial. We assessed whether the quality of radiation therapy intervention was evaluated in Cochrane systematic reviews. METHODS: We searched 416 published Cochrane systematic reviews and identified 67 Cochrane systematic reviews that investigated radiation therapy or radiotherapy as an intervention. For each systematic review, either quality assurance or quality control for the intervention was identified by a description of such processes in the published systematic reviews. RESULTS: Of the 67 Cochrane systematic reviews studied, only two mentioned quality assurance or quality control. CONCLUSIONS: Our findings revealed that 65 of 67 (97%) Cochrane systematic reviews of radiation therapy interventions failed to consider the quality of the intervention. We suggest that advice about the evaluation of intervention quality be added to author support materials.

Follow-up strategies for patients treated for non-metastatic colorectal cancer.

BACKGROUND: It is common clinical practice to follow patients with colorectal cancer (CRC) for several years following their curative surgery or adjuvant therapy, or both. Despite this widespread practice, there is considerable controversy about how often patients should be seen, what tests should be performed, and whether these varying strategies have any significant impact on patient outcomes. This is the second update of a Cochrane Review first published in 2002 and first updated in 2007. OBJECTIVES: To assess the effects of intensive follow-up for patients with non-metastatic colorectal cancer treated with curative intent. SEARCH METHODS: For this update, we searched CENTRAL (2016, Issue 3), MEDLINE (1950 to May 20th, 2016), Embase (1974 to May 20th, 2016), CINAHL (1981 to May 20th, 2016), and Science Citation Index (1900 to May 20th, 2016). We also searched reference lists of articles, and handsearched the Proceedings of the American Society for Radiation Oncology (2011 to 2014). In addition, we searched the following trials registries (May 20th, 2016): ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. We further contacted study authors. No language or publication restrictions were applied to the search strategies. SELECTION CRITERIA: We included only randomised controlled trials comparing different follow-up strategies for participants with non-metastatic CRC treated with curative intent. DATA COLLECTION AND ANALYSIS: Two authors independently determined trial eligibility, performed data extraction, and assessed methodological quality. MAIN RESULTS: We studied 5403 participants enrolled in 15 studies. (We included two new studies in this second update.) Although the studies varied in setting (general practitioner (GP)-led, nurse-led, or surgeon-led) and "intensity" of follow-up, there was very little inconsistency in the results.Overall survival: we found no evidence of a statistical effect with intensive follow-up (hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.78 to 1.02; I² = 4%; P = 0.41; high-quality evidence). There were 1098 deaths among 4786 participants enrolled in 12 studies.Colorectal cancer-specific survival: this did not differ with intensive follow-up (HR 0.93, 95% CI 0.78 to 1.12; I² = 0%; P = 0.45; moderate-quality evidence). There were 432 colorectal cancer deaths among 3769 participants enrolled in seven studies.Relapse-free survival: we found no statistical evidence of effect with intensive follow-up (HR 1.03, 95% CI 0.90 to 1.18; I² = 5%; P = 0.39; moderate-quality evidence). There were 1416 relapses among 5253 participants enrolled in 14 studies.Salvage surgery with curative intent: this was more frequent with intensive follow-up (risk ratio (RR) 1.98, 95% CI 1.53 to 2.56; I² = 31%; P = 0.14; high-quality evidence). There were 457 episodes of salvage surgery in 5157 participants enrolled in 13 studies.Interval (symptomatic) recurrences: these were less frequent with intensive follow-up (RR 0.59, 95% CI 0.41 to 0.86; I² = 66%; P = 0.007; moderate-quality evidence). Three hundred and seventy-six interval recurrences were reported in 3933 participants enrolled in seven studies.Intensive follow-up did not appear to affect quality of life, anxiety, nor depression (reported in three studies).Harms from colonoscopies did not differ with intensive follow-up (RR 2.08, 95% CI 0.11 to 40.17; moderate-quality evidence). In two studies, there were seven colonoscopic complications in 2112 colonoscopies. AUTHORS' CONCLUSIONS: The results of our review suggest that there is no overall survival benefit for intensifying the follow-up of patients after curative surgery for colorectal cancer. Although more participants were treated with salvage surgery with curative intent in the intensive follow-up group, this was not associated with improved survival. Harms related to intensive follow-up and salvage therapy were not well reported.

Partial breast irradiation for early breast cancer.

BACKGROUND: Breast-conserving therapy for women with breast cancer consists of local excision of the tumour (achieving clear margins) followed by radiotherapy (RT). RT is given to sterilize tumour cells that may remain after surgery to decrease the risk of local tumour recurrence. Most true recurrences occur in the same quadrant as the original tumour. Whole breast radiotherapy (WBRT) may not protect against the development of a new primary cancer developing in other quadrants of the breast. In this Cochrane review, we investigated the delivery of radiation to a limited volume of the breast around the tumour bed (partial breast irradiation (PBI)) sometimes with a shortened treatment duration (accelerated partial breast irradiation (APBI)). OBJECTIVES: To determine whether PBI/APBI is equivalent to or better than conventional or hypo-fractionated WBRT after breast-conserving therapy for early-stage breast cancer. SEARCH METHODS: We searched the Cochrane Breast Cancer Group Specialized Register (4 May 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 5), MEDLINE (January 1966 to 4 May 2015), EMBASE (1980 to 4 May 2015), CINAHL (4 May 2015) and Current Contents (4 May 2015). We searched the International Standard Randomised Controlled Trial Number Register (5 May 2015), the World Health Organization's International Clinical Trials Registry Platform (4 May 2015) and ClinicalTrials.gov (17 June 2015). We searched for grey literature: OpenGrey (17 June 2015), reference lists of articles, several conference proceedings and published abstracts, and applied no language restrictions. SELECTION CRITERIA: Randomized controlled trials (RCTs) without confounding, that evaluated conservative surgery plus PBI/APBI versus conservative surgery plus WBRT. Published and unpublished trials were eligible. DATA COLLECTION AND ANALYSIS: Two review authors (BH and ML) performed data extraction and used Cochrane's 'Risk of bias' tool, and resolved any disagreements through discussion. We entered data into Review Manager 5 for analysis. MAIN RESULTS: We included seven RCTs and studied 7586 women of the 8955 enrolled.Local recurrence-free survival appeared worse for women receiving PBI/APBI compared to WBRT (hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.11 to 2.35; six studies, 6820 participants, low-quality evidence). Cosmesis (physician-reported) appeared worse with PBI/APBI (odds ratio (OR) 1.51, 95% CI 1.17 to 1.95, five studies, 1720 participants, low-quality evidence). Overall survival did not differ with PBI/APBI (HR 0.90, 95% CI 0.74 to 1.09, five studies, 6718 participants, high-quality evidence).Late radiation toxicity (subcutaneous fibrosis) appeared worse with PBI/APBI (OR 6.58, 95% CI 3.08 to 14.06, one study, 766 participants, moderate-quality evidence). Acute skin toxicity appeared reduced with PBI/APBI (OR 0.04, 95% CI 0.02 to 0.09, two studies, 608 participants). Telangiectasia (OR 26.56, 95% CI 3.59 to 196.51, 1 study, 766 participants) and radiological fat necrosis (OR 1.58, 95% CI 1.02 to 2.43, three studies, 1319 participants) appeared worse with PBI/APBI. Late skin toxicity (OR 0.21, 95% CI 0.01 to 4.39, two studies, 608 participants) and breast pain (OR 2.17, 95% CI 0.56 to 8.44, one study, 766 participants) appeared not to differ with PBI/APBI.'Elsewhere primaries' (new primaries in the ipsilateral breast) appeared more frequent with PBI/APBI (OR 3.97, 95% CI 1.51 to 10.41, three studies, 3009 participants).We found no clear evidence of a difference for the comparison of PBI/APBI with WBRT for the outcomes of: cause-specific survival (HR 1.08, 95% CI 0.73 to 1.58, five studies, 6718 participants, moderate-quality evidence), distant metastasis-free survival (HR 0.94, 95% CI 0.65 to 1.37, four studies, 3267 participants, moderate-quality evidence), relapse-free survival (HR 1.36, 95% CI 0.88 to 2.09, three studies, 3811 participants), loco-regional recurrence-free survival (HR 1.80, 95% CI 1.00 to 3.25, two studies, 3553 participants) or mastectomy rates (OR 1.20, 95% CI 0.77 to 1.87, three studies, 4817 participants, low-quality evidence). Compliance was met: more than 90% of the women in all studies received the RT they were assigned to receive. We found no data for the outcomes of costs, quality of life or consumer preference. AUTHORS' CONCLUSIONS: It appeared that local recurrence and 'elsewhere primaries' (new primaries in the ipsilateral breast) are increased with PBI/APBI (the difference was small), but we found no evidence of detriment to other oncological outcomes. It appeared that cosmetic outcomes and some late effects were worse with PBI/APBI but its use was associated with less acute skin toxicity. The limitations of the data currently available mean that we cannot make definitive conclusions about the efficacy and safety or ways to deliver of PBI/APBI. We await completion of ongoing trials.

Fraction size in radiation therapy for breast conservation in early breast cancer.

BACKGROUND: Shortening the duration of radiation therapy would benefit women with early breast cancer treated with breast conserving surgery. It may also improve access to radiation therapy by improving efficiency in radiation oncology departments globally. This can only happen if the shorter treatment is as effective and safe as conventional radiation therapy. This is an update of a Cochrane Review first published in 2008 and updated in 2009. OBJECTIVES: To assess the effect of altered radiation fraction size for women with early breast cancer who have had breast conserving surgery. SEARCH METHODS: We searched the Cochrane Breast Cancer Specialised Register (23 May 2015), CENTRAL (The Cochrane Library 2015, Issue 4), MEDLINE (Jan 1996 to May 2015), EMBASE (Jan 1980 to May 2015), the WHO International Clinical Trials Registry Platform (ICTRP) search portal (June 2010 to May 2015) and ClinicalTrials.gov (16 April 2015), reference lists of articles and relevant conference proceedings. No language or publication constraints were applied. SELECTION CRITERIA: Randomised controlled trials of altered fraction size versus conventional fractionation for radiation therapy in women with early breast cancer who had undergone breast conserving surgery. DATA COLLECTION AND ANALYSIS: Two authors performed data extraction independently, with disagreements resolved by discussion. We sought missing data from trial authors. MAIN RESULTS: We studied 8228 women in nine studies. Eight out of nine studies were at low or unclear risk of bias. Altered fraction size (delivering radiation therapy in larger amounts each day but over fewer days than with conventional fractionation) did not have a clinically meaningful effect on: local recurrence-free survival (Hazard Ratio (HR) 0.94, 95% CI 0.77 to 1.15, 7095 women, four studies, high-quality evidence), cosmetic outcome (Risk ratio (RR) 0.90, 95% CI 0.81 to 1.01, 2103 women, four studies, high-quality evidence) or overall survival (HR 0.91, 95% CI 0.80 to 1.03, 5685 women, three studies, high-quality evidence). Acute radiation skin toxicity (RR 0.32, 95% CI 0.22 to 0.45, 357 women, two studies) was reduced with altered fraction size. Late radiation subcutaneous toxicity did not differ with altered fraction size (RR 0.93, 95% CI 0.83 to 1.05, 5130 women, four studies, high-quality evidence). Breast cancer-specific survival (HR 0.91, 95% CI 0.78 to 1.06, 5685 women, three studies, high quality evidence) and relapse-free survival (HR 0.93, 95% CI 0.82 to 1.05, 5685 women, three studies, moderate-quality evidence) did not differ with altered fraction size. We found no data for mastectomy rate. Altered fraction size was associated with less patient-reported (P < 0.001) and physician-reported (P = 0.009) fatigue at six months (287 women, one study). We found no difference in the issue of altered fractionation for patient-reported outcomes of: physical well-being (P = 0.46), functional well-being (P = 0.38), emotional well-being (P = 0.58), social well-being (P = 0.32), breast cancer concerns (P = 0.94; 287 women, one study). We found no data with respect to costs. AUTHORS' CONCLUSIONS: We found that using altered fraction size regimens (greater than 2 Gy per fraction) does not have a clinically meaningful effect on local recurrence, is associated with decreased acute toxicity and does not seem to affect breast appearance, late toxicity or patient-reported quality-of-life measures for selected women treated with breast conserving therapy. These are mostly women with node negative tumours smaller than 3 cm and negative pathological margins.

Clinical implications of the overshoot effect for treatment plan delivery and patient-specific quality assurance for step-and-shoot IMRT.

In this work, overshoot and undershoot effects associated with step-and-shoot IMRT (SSIMRT) delivery on a Varian Clinac 21iX are investigated, and their impact on patient-specific QA point dose measurements and treatment plan delivery are evaluated. Pinnacle3 SSIMRT plans consisting of 5, 10, and 15 identical 5 × 5 cm2 MLC defined segments and MU/segment values of 5 MU, 10 MU, and 20 MU were utilized and delivered at 600/300 MU/min. Independent of the number of segments the overshoot and undershoot at 600 MU/min were approximately ± 10%, ± 5%, and ± 2.5% for 5 MU/segment, 10 MU/segment, and 20 MU/segment, respectively. At 300 MU/min, each of these values is approximately halved. Interfractional variation of these effects (10 fractions), as well as dosimetric variations for intermediate segments, are reduced at the lower dose rate. QA point-dose measurements for a sample (n = 29) of head and neck SSIMRT beams were on average 2.9% (600 MU/min) and 1.7% (300 MU/min) higher than Pinnacle3 planned doses. In comparison for prostate beams (n = 46), measured point doses were 0.8% (600 MU/min) and 0.4% (300 MU/min) higher. The reduction in planned-measured point-dose discrepancies at 300 MU/min can be attributed in part to the inclusion of the first segment (overshoot) in the admixture of segments that deliver measured dose. Pinnacle3 plans for 10/9 head and neck/prostate treatments were adjusted by ± 0.5 MU to include the effects of overshoot and undershoot at 600 MU/min. Comparing original and adjusted plans for each site indicated that the original plan was preferred in 70% and 89% of head and neck and prostate cases, respectively. The disparity between planned and delivered treatment that this suggests can potentially be mitigated by treating SSIMRT at a dose rate below 600 MU/min.

Maastricht Delphi consensus on event definitions for classification of recurrence in breast cancer research.

BACKGROUND: In breast cancer studies, many different endpoints are used. Definitions are often not provided or vary between studies. For instance, "local recurrence" may include different components in similar studies. This limits transparency and comparability of results. This project aimed to reach consensus on the definitions of local event, second primary breast cancer, regional and distant event for breast cancer studies. METHODS: The RAND-UCLA Appropriateness method (modified Delphi method) was used. A Consensus Group of international breast cancer experts was formed, including representatives of all involved clinical disciplines. Consensus was reached in two rounds of online questionnaires and one meeting. RESULTS: Twenty-four international breast cancer experts participated. Consensus was reached on 134 items in four categories. Local event is defined as any epithelial breast cancer or ductal carcinoma in situ (DCIS) in the ipsilateral breast, or skin and subcutaneous tissue on the ipsilateral thoracic wall. Second primary breast cancer is defined as epithelial breast cancer in the contralateral breast. Regional events are breast cancer in ipsilateral lymph nodes. A distant event is breast cancer in any other location. Therefore, this includes metastasis in contralateral lymph nodes and breast cancer involving the sternal bone. If feasible, tissue sampling of a first, solitary, lesion suspected for metastasis is highly recommended. CONCLUSION: This project resulted in consensus-based event definitions for classification of recurrence in breast cancer research. Future breast cancer research projects should adopt these definitions to increase transparency. This should facilitate comparison of results and conducting reviews as well as meta-analysis.

Partial breast irradiation for early breast cancer.

BACKGROUND: Breast conserving therapy for women with breast cancer consists of local excision of the tumour (achieving clear margins) followed by radiation therapy (RT). RT is given to sterilize tumour cells that may remain after surgery to decrease the risk of local tumour recurrence. Most true recurrences occur in the same quadrant as the original tumour. Whole breast RT may not protect against the development of a new primary cancer developing in other quadrants of the breast. In this Cochrane Review, we investigated the role of delivering radiation to a limited volume of the breast around the tumour bed (partial breast irradiation: PBI) sometimes with a shortened treatment duration (accelerated partial breast irradiation: APBI). OBJECTIVES: To determine whether PBI/APBI is equivalent to or better than conventional or hypofractionated WBRT after breast conservation therapy for early-stage breast cancer. SEARCH METHODS: We searched the Cochrane Breast Cancer Group Specialised Register (07 November 2013), CENTRAL (2014, Issue 3), MEDLINE (January 1966 to 11 April 2014), EMBASE (1980 to 11 April 2014), CINAHL (11 April 2014) and Current Contents (11 April 2014). Also we searched the International Standard Randomised Controlled Trial Number Register, the World Health Organization's International Clinical Trials Registry Platform (07 November 2013) and US clinical trials registry (www.clinicaltrials.gov) (22 April 2014). We searched for grey literature: Open Grey (23 April 2014), reference lists of articles, a number of conference proceedings and published abstracts, and did not apply any language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) without confounding and evaluating conservative surgery plus PBI/APBI versus conservative surgery plus whole breast RT. We included both published and unpublished trials. DATA COLLECTION AND ANALYSIS: Three review authors (ML, DF and BH) performed data extraction and resolved any disagreements through discussion. We entered data into Review Manager for analysis. BH and ML assessed trials, graded the methodological quality using Cochrane's Risk of Bias tool and resolved any disagreements through discussion. MAIN RESULTS: We included four RCTs that had 2253 women. Two older trials examined RT techniques which do not reflect current practice and one trial had a short follow-up. We downgraded the quality of the evidence for our key outcomes due to risk of bias. Taken together with other GRADE recommendations, the quality of evidence for our outcomes was very low to low. For the comparison of partial breast irradiation/accelerated breast irradiation (PBI/APBI) with whole breast irradiation (WBRT), local recurrence-free survival appeared worse (Hazard Ratio (HR) 1.74, 95% confidence interval (CI) 1.23 to 2.45; three trials, 1140 participants, very low quality evidence). Cosmesis appeared improved with PBI/APBI in a single trial (OR 0.40, 95% CI 0.23 to 0.72; one trial, 241 participants, very low quality evidence), but late toxicity (telangiectasia OR 4.41, 95% CI 3.21 to 6.05; very low quality evidence, 708 participants) and subcutaneous fibrosis (OR 4.27, 95% CI 3.04 to 6.01; one trial, 710 participants, very low quality evidence) appeared increased in another trial. We found no clear evidence of a difference for the comparison of PBI/APBI versus WBRT for the outcomes of: overall survival (HR 0.99, 95% CI 0.83 to 1.18; three trials, 1140 participants, very low quality evidence), cause-specific survival (HR 0.95, 95% CI 0.74 to 1.22; two trials, 966 participants, low evidence quality), distant metastasis-free survival (HR 1.02, 95% CI 0.81 to 1.28; 1140 participants, low quality evidence), subsequent mastectomy rate (OR 0.20, 95% CI 0.01 to 4.21; 258 participants, low quality evidence) and relapse-free survival (HR 0.99, 95% CI 0.53 to 1.85; 258 participants, low quality evidence). We found no data for the outcomes of acute toxicity, new ipsilateral breast primaries, costs, quality of life or consumer preference. AUTHORS' CONCLUSIONS: The limitations of the data currently available mean that we cannot make definitive conclusions about the efficacy and safety or ways to deliver of PBI/APBI. We await completion of ongoing trials.

Sequencing of chemotherapy and radiotherapy for early breast cancer.

BACKGROUND: After surgery for localised breast cancer, radiotherapy (RT) improves both local control and breast cancer-specific survival. In patients at risk of harbouring micro-metastatic disease, adjuvant chemotherapy (CT) improves 15-year survival. However, the best sequence of administering these two types of adjuvant therapy for early-stage breast cancer is unclear. OBJECTIVES: To determine the effects of different sequencing of adjuvant CT and RT for women with early breast cancer. SEARCH METHODS: An updated search was carried out in the Cochrane Breast Cancer Group's Specialised Register (20 May 2011), MEDLINE (14 December 2011), EMBASE (20 May 2011) and World Health Organization (WHO) International Clinical Trials Registry Platform (20 May 2011). Details of the search strategy and methods of coding for the Specialised Register are described in the Group's module in The Cochrane Library. We extracted studies that had been coded as 'early', 'chemotherapy' and 'radiotherapy'. SELECTION CRITERIA: We included randomised controlled trials evaluating different sequencing of CT and RT. DATA COLLECTION AND ANALYSIS: We assessed the eligibility and quality of the identified studies and extracted data from the published reports of the included trials. We derived odds ratios (OR) and hazard ratios (HR) from the available numerical data. Toxicity data were extracted, where reported. We used a fixed-effect model for meta-analysis and conducted analyses on the basis of the method of sequencing of the two treatments. MAIN RESULTS: Three trials reporting two different sequencing comparisons were identified. There were no significant differences between the various methods of sequencing adjuvant therapy for local recurrence-free survival, overall survival, relapse-free survival and metastasis-free survival based on 1166 randomised women in three trials. Concurrent chemoradiation increased anaemia (OR 1.54; 95% confidence interval (CI) 1.10 to 2.15), telangiectasia (OR 3.85; 95% CI 1.37 to 10.87) and pigmentation (OR 15.96; 95% CI 2.06 to 123.68). Treated women did not report worse cosmesis with concurrent chemoradiation but physician-reported assessments did (OR 1.14; 95% CI 0.42 to 3.07). Other measures of toxicity did not differ between the two types of sequencing. On the basis of one trial (244 women), RT before CT was associated with an increased risk of neutropenic sepsis (OR 2.96; 95% CI 1.26 to 6.98) compared with CT before RT, but other measures of toxicity did not differ. AUTHORS' CONCLUSIONS: The data included in this review, from three well-conducted randomised trials, suggest that different methods of sequencing CT and RT do not appear to have a major effect on recurrence or survival for women with breast cancer if RT is commenced within seven months after surgery.

A retrospective analysis of survival outcomes for two different radiotherapy fractionation schedules given in the same overall time for limited stage small cell lung cancer.

PURPOSE: To compare survival outcomes for two fractionation schedules of thoracic radiotherapy, both given over 3 weeks, in patients with limited stage small cell lung cancer (LS-SCLC). METHODS AND MATERIALS: At Radiation Oncology Mater Centre (ROMC) and the Royal Brisbane & Women's Hospital (RBWH), patients with LS-SCLC treated with curative intent are given radiotherapy (with concurrent chemotherapy) to a dose of either 40 Gy in 15 fractions ('the 40 Gy/15# group') or 45 Gy in 30 fractions ('the 45 Gy/30# group'). The choice largely depends on institutional preference. Both these schedules are given over 3 weeks, using daily and twice-daily fractionation respectively. The records of all such patients treated from January 2000 to July 2009 were retrospectively reviewed and survival outcomes between the two groups compared. RESULTS: Of 118 eligible patients, there were 38 patients in the 40 Gy/15# group and 41 patients in the 45 Gy/30# group. The median relapse-free survival time was 12 months in both groups. Median overall survival was 21 months (95% CI 2-37 months) in the 40 Gy/15# group and 26 months (95% CI 1-48 months) in the 45 Gy/30# group. The 5-year overall survival rates were 20% and 25%, respectively (P = 0.24). On multivariate analysis, factors influencing overall survival were: whether prophylactic cranial irradiation (PCI) was given (P = 0.01) and whether salvage chemotherapy was given at the time of relapse (P = 0.057). CONCLUSIONS: Given the small sample size, the potential for selection bias and the retrospective nature of our study it is not possible to draw firm conclusions regarding the efficacy of hypofractionated thoracic radiotherapy compared with hyperfractionated accelerated thoracic radiotherapy however hypofractionated radiotherapy may result in equivalent relapse-free survival.

Multidisciplinary clinic care improves adherence to best practice in head and neck cancer.

PURPOSE: Multidisciplinary team (MDT) care is widely accepted as best practice for patients with head and neck cancer, although there is little evidence that MDT care improves head and neck cancer related outcomes. This study aims to determine the impact of MDT care on measurable clinical quality indicators (CQIs) associated with improved patient outcomes. MATERIALS AND METHODS: Patients treated for head and neck cancer at Ipswich Hospital from 2001 to 2008 were identified. Comparisons were made in adherence to CQIs between patients treated before (pre MDT) and after (post MDT) the introduction of the MDT. Associations were tested using the Chi-square and Whitney U-test. RESULTS: Treatment post MDT was associated with greater adherence to CQIs than pre MDT. Post MDT had higher rates of: dental assessment (59% versus 22%, p<.0001), nutritional assessment (57% versus 39%, p=.015), PET staging (41% versus 2%, p<.0001), chemo-radiotherapy (CRT) for locally advanced disease (66% versus 16%, p<.0001) and use of adjuvant CRT for high risk disease (49% versus 16%, p<.0001). The interval between surgery and radiotherapy was shorter in the post MDT group (p=.009) as was the mean length of hospitalization (p=.002). CONCLUSIONS: This study highlights the measurable advantages of MDT care over the standard, less formalized, referral process.

Split-course, high-dose palliative pelvic radiotherapy for locally progressive hormone-refractory prostate cancer.

PURPOSE: Local progression, in patients with hormone-refractory prostate cancer, often causes significant morbidity. Pelvic radiotherapy (RT) provides effective palliation in this setting, with most published studies supporting the use of high-dose regimens. The aim of the present study was to examine the role of split-course hypofractionated RT used at our institution in treating this group of patients. METHODS AND MATERIALS: A total of 34 men with locoregionally progressive hormone-refractory prostate cancer, treated with a split course of pelvic RT (45-60 Gy in 18-24 fractions) between 2000 and 2008 were analyzed. The primary endpoints were the response rate and actuarial locoregional progression-free survival. Secondary endpoints included overall survival, compliance, and acute and late toxicity. RESULTS: The median age was 71 years (range, 53-88). Treatment resulted in an overall initial response rate of 91%, a median locoregional progression-free survival of 43 months, and median overall survival of 28 months. Compliance was excellent and no significant late toxicity was reported. CONCLUSIONS: The split course pelvic RT described has an acceptable toxicity profile, is effective, and compares well with other high-dose palliative regimens that have been previously reported.

Adjuvant radiotherapy following radical prostatectomy for prostate cancer.

BACKGROUND: Men who have a radical prostatectomy (RP) for prostate cancer that does not involve lymph nodes, but extends beyond the prostate capsule into the seminal vesicles or to surgical margins, are at increased risk of relapse. In men with these high risk factors, radiotherapy (RT) directed at the prostate bed after surgery may reduce this risk, and be curative. OBJECTIVES: To evaluate the effect of adjuvant RT following RP for prostate cancer in men with high risk features compared with RP. SEARCH METHODS: We searched the Cochrane Prostatic Diseases and Urological Cancers Specialised Register (23 February 2011), the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE (January 1966 to February 2011), PDQ® (Physician Data Query) trial registry databases for ongoing studies (2 November 2010), reference lists from selected studies and reviews, and handsearched relevant conference proceedings. SELECTION CRITERIA: Randomised controlled trials (RCT) comparing RP followed by RT with RP alone. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the studies for inclusion and bias and extracted data for analysis. Authors were contacted to clarify data and obtain missing information. MAIN RESULTS: We found three RCTs involving 1815 men. Adjuvant RT following prostatectomy did not affect overall survival at 5 years (RD (risk difference) 0.00; 95% CI -0.03 to 0.03), but improved survival at 10 years (RD -0.11; 95% CI -0.20 to -0.02). Adjuvant RT did not improve prostate cancer-specific mortality at 5 years (RD -0.01; 95% CI -0.03 to 0.00). Adjuvant RT did not reduce metastatic disease at 5 years (RD -0.00; 95% CI -0.04 to 0.03), but reduced it at 10 years (RD -0.11; 95% CI -0.20 to -0.01). It improved local control at 5 and 10 years (RD -0.10; 95% CI -0.13 to -0.06 and RD -0.14; 95% CI -0.21 to -0.07, respectively), and biochemical progression-free survival at 5 years and 10 years (RD -0.16; 95% CI -0.21 to -0.11 and RD -0.29; 95% CI -0.39 to -0.19, respectively). There were no data for clinical disease-free survival. Adjuvant RT increased acute and late gastrointestinal toxicity [do you have the rd for this?], urinary stricture (RD 0.05; 95% CI 0.01 to 0.09) and incontinence (RD 0.04; 95% CI 0.01 to 0.08). It did not increase erectile dysfunction or degrade quality of life (RD 0.01; 95% CI -0.06 to -0.26), but with limited data. AUTHORS' CONCLUSIONS: Adjuvant RT after RP improves overall survival and reduces the rate of distant metastases, but these effects are only evident with longer follow up. At 5 and 10 years it improves local control and reduces the risk of biochemical failure, although the latter is not a clinical endpoint. Moderate or severe acute and late toxicity is minimal. There is an increased risk of urinary stricture and incontinence, but no detriment to quality of life, based on limited data. Given that the majority of men who have undergone a RP have a longer life expectancy, radiotherapy should be considered for those with high-risk features following radical prostatectomy. The optimal timing is unclear.

Fraction size in radiation treatment for breast conservation in early breast cancer.

BACKGROUND: Shortening the duration of radiation therapy would benefit women with early breast cancer treated with breast conserving surgery. It may also improve access to radiation therapy by improving efficiency in radiation oncology departments globally. This can only happen if the shorter treatment is as effective and safe as conventional radiation therapy. This is an updated version of the original Cochrane Review published in Issue 3, 2008. OBJECTIVES: To determine the effect of altered radiation fraction size on outcomes for women with early breast cancer who have undergone breast conserving surgery. SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group Specialised Register, MEDLINE, EMBASE and the WHO ICTRP search portal to June 2009, reference lists of articles and relevant conference proceedings. We applied no language constraints. SELECTION CRITERIA: Randomised controlled trials of unconventional versus conventional fractionation in women with early breast cancer who had undergone breast conserving surgery. DATA COLLECTION AND ANALYSIS: The authors performed data extraction independently, with disagreements resolved by discussion. We sought missing data from trial authors. MAIN RESULTS: Four trials reported on 7095 women. The women were highly selected: tumours were node negative and 89.8% were smaller than 3 cm. Where the breast size was known, 87% had small or medium breasts. The studies were of low to medium quality. Unconventional fractionation (delivering radiation therapy in larger amounts each day but over fewer days than with conventional fractionation) did not affect: (1) local recurrence risk ratio (RR) 0.97 (95% CI 0.76 to 1.22, P = 0.78), (2) breast appearance RR 1.17 (95% CI 0.98 to 1.39, P = 0.09), (3) survival at five years RR 0.89 (95% CI 0.77 to 1.04, P = 0.16). Acute skin toxicity was decreased with unconventional fractionation: RR 0.21 (95% CI 0.07 to 0.64, P = 0.007). AUTHORS' CONCLUSIONS: Two new studies have been published since the last version of the review, altering our conclusions. We have evidence from four low to medium quality randomised trials that using unconventional fractionation regimens (greater than 2 Gy per fraction) does not affect local recurrence, is associated with decreased acute toxicity and does not seem to affect breast appearance or late toxicity for selected women treated with breast conserving therapy. These are mostly women with node negative tumours smaller than 3 cm and negative pathological margins. Long-term follow up (> 5 years) is available for a small proportion of the patients randomised. Longer follow up is required for a more complete assessment of the effect of altered fractionation.