Is breast seroma after tumour resection associated with patient-reported breast appearance change following radiotherapy? Results from the IMPORT HIGH (CRUK/06/003) trial.

Background Seroma describes a collection of serous fluid within a cavity, occurring following surgery. Seroma is associated with normal tissue effects (NTE) following breast radiotherapy, as reported by clinicians and on photographs. This study investigates the association between seroma and the NTE breast appearance change collected using patient-reported outcome measures (PROMs) in IMPORT HIGH, as well as investigating the association between breast appearance change and patient/tumour/treatment factors.Methods Case-control methodology was used for seroma analysis within IMPORT HIGH. Cases were patients reporting moderate/marked breast appearance change and controls reported none/mild changes at year-3. One control was selected at random for each case. Seromas were graded as not visible/subtle or visible/highly visible on CT radiotherapy planning scans. Logistic regression tested associations, adjusting for patient/tumour/treatment factors.Results 1078/1149 patients consented to PROMs, of whom 836 (78%) reported whether they had 3-year breast appearance change; 231 cases and 231 controls were identified. 304/462 (66%) patients received chemotherapy. Seroma prevalence was 20% (41/202) in cases and 16% (32/205) in controls, and less frequent in patients receiving adjuvant chemotherapy [10% (24/246) compared with 29% (40/138) without]. Visible seroma was not significantly associated with breast appearance change [OR 1.38 (95%CI 0.83-2.29), p = 0.219]. Larger tumour size, haematoma, current smoking and body image concerns at baseline were independent risk factors.Conclusions Seroma was not associated with patient-reported breast appearance change, but haematoma and smoking were significant risk factors. Lack of association may be related to lower prevalence of seroma compared with previous reports, perhaps reflecting patients receiving adjuvant chemotherapy in whom seroma resolves prior to radiotherapy

A multicentre study of the evidence for customized margins in photon breast boost radiotherapy.

Objective To determine if subsets of patients may benefit from smaller or larger margins when using laser setup and bony anatomy verification of breast tumour bed (TB) boost radiotherapy (RT).Methods Verification imaging data acquired using cone-beam CT, megavoltage CT or two-dimensional kilovoltage imaging on 218 patients were used (1574 images). TB setup errors for laser-only setup (dlaser) and for bony anatomy verification (dbone) were determined using clips implanted into the TB as a gold standard for the TB position. Cases were grouped by centre-, patient- and treatment-related factors, including breast volume, TB position, seroma visibility and surgical technique. Systematic (Σ) and random (σ) TB setup errors were compared between groups, and TB planning target volume margins (MTB) were calculated.Results For the study population, Σlaser was between 2.8 and 3.4 mm, and Σbone was between 2.2 and 2.6 mm, respectively. Females with larger breasts (p = 0.03), easily visible seroma (p ≤ 0.02) and open surgical technique (p ≤ 0.04) had larger Σlaser. Σbone was larger for females with larger breasts (p = 0.02) and lateral tumours (p = 0.04). Females with medial tumours (p < 0.01) had smaller Σbone.Conclusion If clips are not used, margins should be 8 and 10 mm for bony anatomy verification and laser setup, respectively. Individualization of TB margins may be considered based on breast volume, TB and seroma visibility.Advances in knowledge Setup accuracy using lasers and bony anatomy is influenced by patient and treatment factors. Some patients may benefit from clip-based image guidance more than others

Patient-Reported Outcomes Over 5 Years After Whole- or Partial-Breast Radiotherapy: Longitudinal Analysis of the IMPORT LOW (CRUK/06/003) Phase III Randomized Controlled Trial.

Purpose IMPORT LOW demonstrated noninferiority of partial-breast and reduced-dose radiotherapy versus whole-breast radiotherapy for local relapse and similar or reduced toxicity at 5 years. Comprehensive patient-reported outcome measures collected at serial time points are now reported.Patients and methods IMPORT LOW recruited women with low-risk breast cancer after breast-conserving surgery. Patients were randomly assigned to 40 Gy whole-breast radiotherapy (control), 36 Gy whole-breast and 40 Gy partial-breast radiotherapy (reduced-dose), or 40 Gy partial-breast radiotherapy only (partial-breast) in 15 fractions. European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires Core 30 and Breast Cancer-Specific Module, Body Image Scale, protocol-specific items, and the Hospital Anxiety and Depression Scale were administered at baseline, 6 months, and 1, 2, and 5 years. Patterns of moderate/marked adverse effects (AEs) were assessed using longitudinal regression models, and baseline predictors were investigated.Results A total of 41 of 71 centers participated in the patient-reported outcome measures substudy; 1,265 (95%) of 1,333 patients consented, and 557 (58%) of 962 reported no moderate/marked AEs at 5 years. Breast appearance change was most prevalent and persisted over time (approximately 20% at each time point). Prevalence of breast hardness, pain, oversensitivity, edema, and skin changes reduced over time ( P < .001 for each), whereas breast shrinkage increased ( P < .001). Analysis by treatment group showed average number of AEs per person was lower in partial-breast (incidence rate ratio, 0.77; 95% CI, 0.71 to 0.84; P < .001) and reduced-dose (incidence rate ratio, 0.83; 95% CI, 0.76 to 0.90; P < .001) versus whole-breast group and decreased over time in all groups. Younger age, larger breast size/surgical deficit, lymph node positivity, and higher levels of anxiety/depression were baseline predictors of subsequent AE reporting.Conclusion Most AEs reduced over time, with fewer AEs in the partial-breast and reduced-dose groups. Baseline predictors for AE reporting were identified. These findings will facilitate informed discussion and shared decision making for future patients receiving moderately hypofractionated breast radiotherapy

Can patient-reported outcomes be used instead of clinician-reported outcomes and photographs as primary endpoints of late normal tissue effects in breast radiotherapy trials? Results from the IMPORT LOW trial.

BACKGROUND: In an era of low local relapse rates after adjuvant breast radiotherapy, risks of late normal-tissue effects (NTE) need to be balanced against risk of relapse. NTE are assessed using patient-reported outcome measures (PROMs), clinician-reported outcomes (CRO) and photographs. This analysis investigates whether PROMs can be used as primary NTE endpoints in breast radiotherapy trials. METHODS: Analyses were conducted within IMPORT LOW (ISRCTN12852634) at 2 and 5 years. NTE were recorded by CRO, photographs and PROMs. Measures of agreement tested concordance, risk ratios for radiotherapy groups were compared, and influence of baseline characteristics on concordance investigated. RESULTS: In 1095 patients who consented to PROMS and photographs, PROMs were available at 2 and/or 5 years for 976 patients, of whom 909 had CRO and 844 had photographs. Few patients had moderate/marked NTE, irrespective of method used (eg. 19% patients and 9% clinicians reported breast shrinkage at year-5). Patients reported more NTE than assessed from CRO or photographs (p < 0.001 for most NTE). Concordance between assessments was poor on an individual patient level; eg. for year-5 breast shrinkage, % agreement = 48% and weighted kappa = 0.17. Risk ratios comparing radiotherapy schedules were consistent between PROMs and CRO or photographs. CONCLUSIONS: Few patients had moderate/marked NTE irrespective of method used. Patients reported more NTE than CRO and photographs, therefore NTE may be underestimated if PROMs are not used. Despite poor concordance between methods, effect sizes from PROMs were consistent with CRO and photographs, suggesting PROMs can be used as primary NTE endpoints in breast radiotherapy trials

Is breast seroma after tumour resection associated with patient-reported breast appearance change following radiotherapy? Results from the IMPORT HIGH (CRUK/06/003) trial.

BACKGROUND: Seroma describes a collection of serous fluid within a cavity, occurring following surgery. Seroma is associated with normal tissue effects (NTE) following breast radiotherapy, as reported by clinicians and on photographs. This study investigates the association between seroma and the NTE breast appearance change collected using patient-reported outcome measures (PROMs) in IMPORT HIGH, as well as investigating the association between breast appearance change and patient/tumour/treatment factors. METHODS: Case-control methodology was used for seroma analysis within IMPORT HIGH. Cases were patients reporting moderate/marked breast appearance change and controls reported none/mild changes at year-3. One control was selected at random for each case. Seromas were graded as not visible/subtle or visible/highly visible on CT radiotherapy planning scans. Logistic regression tested associations, adjusting for patient/tumour/treatment factors. RESULTS: 1078/1149 patients consented to PROMs, of whom 836 (78%) reported whether they had 3-year breast appearance change; 231 cases and 231 controls were identified. 304/462 (66%) patients received chemotherapy. Seroma prevalence was 20% (41/202) in cases and 16% (32/205) in controls, and less frequent in patients receiving adjuvant chemotherapy [10% (24/246) compared with 29% (40/138) without]. Visible seroma was not significantly associated with breast appearance change [OR 1.38 (95%CI 0.83-2.29), p = 0.219]. Larger tumour size, haematoma, current smoking and body image concerns at baseline were independent risk factors. CONCLUSIONS: Seroma was not associated with patient-reported breast appearance change, but haematoma and smoking were significant risk factors. Lack of association may be related to lower prevalence of seroma compared with previous reports, perhaps reflecting patients receiving adjuvant chemotherapy in whom seroma resolves prior to radiotherapy

Patient-Reported Outcomes Over 5 Years After Whole- or Partial-Breast Radiotherapy: Longitudinal Analysis of the IMPORT LOW (CRUK/06/003) Phase III Randomized Controlled Trial.

PURPOSE: IMPORT LOW demonstrated noninferiority of partial-breast and reduced-dose radiotherapy versus whole-breast radiotherapy for local relapse and similar or reduced toxicity at 5 years. Comprehensive patient-reported outcome measures collected at serial time points are now reported. PATIENTS AND METHODS: IMPORT LOW recruited women with low-risk breast cancer after breast-conserving surgery. Patients were randomly assigned to 40 Gy whole-breast radiotherapy (control), 36 Gy whole-breast and 40 Gy partial-breast radiotherapy (reduced-dose), or 40 Gy partial-breast radiotherapy only (partial-breast) in 15 fractions. European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires Core 30 and Breast Cancer-Specific Module, Body Image Scale, protocol-specific items, and the Hospital Anxiety and Depression Scale were administered at baseline, 6 months, and 1, 2, and 5 years. Patterns of moderate/marked adverse effects (AEs) were assessed using longitudinal regression models, and baseline predictors were investigated. RESULTS: A total of 41 of 71 centers participated in the patient-reported outcome measures substudy; 1,265 (95%) of 1,333 patients consented, and 557 (58%) of 962 reported no moderate/marked AEs at 5 years. Breast appearance change was most prevalent and persisted over time (approximately 20% at each time point). Prevalence of breast hardness, pain, oversensitivity, edema, and skin changes reduced over time ( P < .001 for each), whereas breast shrinkage increased ( P < .001). Analysis by treatment group showed average number of AEs per person was lower in partial-breast (incidence rate ratio, 0.77; 95% CI, 0.71 to 0.84; P < .001) and reduced-dose (incidence rate ratio, 0.83; 95% CI, 0.76 to 0.90; P < .001) versus whole-breast group and decreased over time in all groups. Younger age, larger breast size/surgical deficit, lymph node positivity, and higher levels of anxiety/depression were baseline predictors of subsequent AE reporting. CONCLUSION: Most AEs reduced over time, with fewer AEs in the partial-breast and reduced-dose groups. Baseline predictors for AE reporting were identified. These findings will facilitate informed discussion and shared decision making for future patients receiving moderately hypofractionated breast radiotherapy.We acknowledge support from Cancer Research UK (grant number C1491/A6035), the National Institute for Health Research (NIHR) Cancer Research Network (CRN), National Health Service Research Scotland, Health and Care Research Wales and the National Institute of Health Research Royal Marsden/ Institute of Cancer Research Biomedical Research Centre. In addition Dr Charlotte Coles is supported by the Cambridge National Institute of Health Research Biomedical Research Centre. Dr Indrani Bhattacharya is supported by a Cancer Research UK clinical trial fellowship (C1491/A8895)

Is breast seroma after tumour resection associated with patient-reported breast appearance change following radiotherapy? Results from the IMPORT HIGH (CRUK/06/003) trial.

BACKGROUND: Seroma describes a collection of serous fluid within a cavity, occurring following surgery. Seroma is associated with normal tissue effects (NTE) following breast radiotherapy, as reported by clinicians and on photographs. This study investigates the association between seroma and the NTE breast appearance change collected using patient-reported outcome measures (PROMs) in IMPORT HIGH, as well as investigating the association between breast appearance change and patient/tumour/treatment factors. METHODS: Case-control methodology was used for seroma analysis within IMPORT HIGH. Cases were patients reporting moderate/marked breast appearance change and controls reported none/mild changes at year-3. One control was selected at random for each case. Seromas were graded as not visible/subtle or visible/highly visible on CT radiotherapy planning scans. Logistic regression tested associations, adjusting for patient/tumour/treatment factors. RESULTS: 1078/1149 patients consented to PROMs, of whom 836 (78%) reported whether they had 3-year breast appearance change; 231 cases and 231 controls were identified. 304/462 (66%) patients received chemotherapy. Seroma prevalence was 20% (41/202) in cases and 16% (32/205) in controls, and less frequent in patients receiving adjuvant chemotherapy [10% (24/246) compared with 29% (40/138) without]. Visible seroma was not significantly associated with breast appearance change [OR 1.38 (95%CI 0.83-2.29), p = 0.219]. Larger tumour size, haematoma, current smoking and body image concerns at baseline were independent risk factors. CONCLUSIONS: Seroma was not associated with patient-reported breast appearance change, but haematoma and smoking were significant risk factors. Lack of association may be related to lower prevalence of seroma compared with previous reports, perhaps reflecting patients receiving adjuvant chemotherapy in whom seroma resolves prior to radiotherapy

A multicentre study of the evidence for customized margins in photon breast boost radiotherapy.

OBJECTIVE: To determine if subsets of patients may benefit from smaller or larger margins when using laser setup and bony anatomy verification of breast tumour bed (TB) boost radiotherapy (RT). METHODS: Verification imaging data acquired using cone-beam CT, megavoltage CT or two-dimensional kilovoltage imaging on 218 patients were used (1574 images). TB setup errors for laser-only setup (dlaser) and for bony anatomy verification (dbone) were determined using clips implanted into the TB as a gold standard for the TB position. Cases were grouped by centre-, patient- and treatment-related factors, including breast volume, TB position, seroma visibility and surgical technique. Systematic (Σ) and random (σ) TB setup errors were compared between groups, and TB planning target volume margins (MTB) were calculated. RESULTS: For the study population, Σlaser was between 2.8 and 3.4 mm, and Σbone was between 2.2 and 2.6 mm, respectively. Females with larger breasts (p = 0.03), easily visible seroma (p ≤ 0.02) and open surgical technique (p ≤ 0.04) had larger Σlaser. Σbone was larger for females with larger breasts (p = 0.02) and lateral tumours (p = 0.04). Females with medial tumours (p < 0.01) had smaller Σbone. CONCLUSION: If clips are not used, margins should be 8 and 10 mm for bony anatomy verification and laser setup, respectively. Individualization of TB margins may be considered based on breast volume, TB and seroma visibility. Advances in knowledge: Setup accuracy using lasers and bony anatomy is influenced by patient and treatment factors. Some patients may benefit from clip-based image guidance more than others