Accelerated Partial Breast Irradiation Using 5 Daily Fractions: A Prospective, Phase 2, Multicenter Trial of Cosmetic Outcomes and Toxicity-ACCEL Final Results.

PURPOSE: This study investigated the cosmetic degradation and toxicity for an accelerated partial breast irradiation (APBI) prescription delivered in 5 fractions over 1 week and compared the outcomes with those of whole breast irradiation (WBI). METHODS AND MATERIALS: The trial was a multicenter, single-arm, phase 2 prospective cohort study. Eligible women 50 years of age or older with estrogen receptor-positive and human epidermal growth factor receptor 2-negative invasive ductal carcinoma or ductal carcinoma in situ after breast-conserving surgery received 27 Gy in 5 daily fractions of APBI. The primary endpoint was noninferiority of 2-year cosmesis using the RAPID trial's WBI arm as the control arm. A global consensus cosmetic score using a European Organisation for Research and Treatment of Cancer rating scale score of excellent, good, fair, or poor for each patient at baseline and 2 years was generated by a panel of 5 radiation oncologists using photographs of treated and untreated breasts. RESULTS: From 2016 to 2019, 298 eligible women were enrolled. By the 2-year follow-up, 76 patients had been lost or withdrawn and 3 had died, resulting in 219 patients available for complete, 2-year photographic cosmetic evaluation. The median follow-up for all participants was 4.7 years (IQR, 3.8-5.5 years). No patient had a fair or poor cosmetic score at the 2-year evaluation. Cosmesis was better or unchanged for 97% of patients and worse for 3% (excellent to good), and no cosmetic failures occurred. The confidence intervals were 0.88 (0.86-0.90) and 1.00 (0.99-1.00) for the RAPID and ACCEL trials, respectively. CONCLUSIONS: Cosmetic degradation with 5 daily treatments of the ACCEL trial's APBI intervention is noninferior to the WBI arm of the RAPID trial.

Radiation doses and fractionation schedules in non-low-risk ductal carcinoma in situ in the breast (BIG 3-07/TROG 07.01): a randomised, factorial, multicentre, open-label, phase 3 study.

BACKGROUND: Whole breast irradiation (WBI) after conservative surgery for ductal carcinoma in situ (DCIS) reduces local recurrence. We investigated whether a tumour bed boost after WBI improved outcomes, and examined radiation dose fractionation sensitivity for non-low-risk DCIS. METHODS: The study was an international, randomised, unmasked, phase 3 trial involving 136 participating centres of six clinical trials organisations in 11 countries (Australia, New Zealand, Singapore, Canada, the Netherlands, Belgium, France, Switzerland, Italy, Ireland, and the UK). Eligible patients were women aged 18 years or older with unilateral, histologically proven, non-low-risk DCIS treated by breast-conserving surgery with at least 1 mm of clear radial resection margins. They were assigned to one of four groups (1:1:1:1) of no tumour bed boost versus boost after conventional versus hypofractionated WBI, or randomly assigned to one of two groups (1:1) of no boost versus boost after each centre prespecified conventional or hypofractionated WBI. The conventional WBI used was 50 Gy in 25 fractions, and hypofractionated WBI was 42·5 Gy in 16 fractions. A boost dose of 16 Gy in eight fractions, if allocated, was delivered after WBI. Patients and clinicians were not masked to treatment allocation. The primary endpoint was time to local recurrence. This trial is registered with ClinicalTrials.gov (NCT00470236). FINDINGS: Between June 25, 2007, and June 30, 2014, 1608 patients were randomly assigned to have no boost (805 patients) or boost (803 patients). Conventional WBI was given to 831 patients, and hypofractionated WBI was given to 777 patients. Median follow-up was 6·6 years. The 5-year free-from-local-recurrence rates were 92·7% (95% CI 90·6-94·4%) in the no-boost group and 97·1% (95·6-98·1%) in the boost group (hazard ratio 0·47; 0·31-0·72; p<0·001). The boost group had higher rates of grade 2 or higher breast pain (10% [8-12%] vs 14% [12-17%], p=0·003) and induration (6% [5-8%] vs 14% [11-16%], p<0·001). INTERPRETATION: In patients with resected non-low-risk DCIS, a tumour bed boost after WBI reduced local recurrence with an increase in grade 2 or greater toxicity. The results provide the first randomised trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control. The international scale of the study supports the generalisability of the results. FUNDING: National Health and Medical Research Council of Australia, Susan G Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, Canadian Cancer Trials Group.

Risk factors for psychological morbidity and the protective role of coping self-efficacy in young women with breast cancer early in diagnosis: a national multicentre cohort study.

PURPOSE: Young women with breast cancer (YWBC) are an understudied population and there are limited data on risk factors for psychological morbidity early in diagnosis. We examined psychological morbidity (anxiety, depression, stress symptoms), well-being and associated risk factors. METHODS: A total of 845 women from a pan-Canadian, multicentre inception cohort study of YWBC (age ≤ 40) who completed Patient Reported Outcome Measures (PROMs) after their initial surgical consultation and prior to surgical or other treatments were included. Multivariate regression analyses identified risk factors (i.e. parenting young children) associated with psychological morbidity and whether coping self-efficacy was protective. RESULTS: Rates of clinically significant anxiety (n = 683, 69.1%) and depression (n = 422, 42.7%) were high but lower for stress symptoms (n = 67, 6.8%). Probability of anxiety was high for women with a previous history of depression (OR 2.02, P = 0.03, CI 1.09-3.74) and working full-time (OR 1.76, P = 0.05 CI 1.02-2.77). Whereas, pre-existing depression (OR 2.91, P = 0.01, CI 1.36-6.01), younger children (age ≤ 10) (OR 1.69, P = 0.05, CI 1.01-2.93), and income > $100,000 (OR 2.06, P = 0.02, CI 1.18-3.64) were risk factors for depression. Coping self-efficacy was protective with a decreased risk of anxiety (OR 0.11, P ≤ 0.01 CI 0.04-0.28), depression (OR 0.03, P ≤ .01, CI 0.01-0.16), stress symptoms (OR 0.17, P ≤ .01, CI 0.04-0.65) and higher psychosocial well-being with a gain of 19.68 points (P < 0.01) for high levels of CSE (> mean plus 1 SD). Those with lower levels of neurosis had less negative outcomes. CONCLUSION: Young women with breast cancer are vulnerable to psychological morbidity early in diagnosis, particularly those with low coping self-efficacy and may benefit from earlier supportive care.

A retrospective analysis to demonstrate achievable dosimetry for the left anterior descending artery in left-sided breast cancer patients treated with radiotherapy.

PURPOSE: To demonstrate achievable dose for the left anterior descending artery (LAD) for left-sided breast cancer patients. METHODS: A retrospective analysis was conducted on all left-sided breast cancer patients receiving whole breast or post-mastectomy chest wall irradiation between 2013 and 2018. All patients in this study were treated with tangent-based techniques with the LAD prospectively contoured as routine clinical care. This large patient cohort was used to benchmark achievable mean doses to the LAD in the context of heart dose. The primary cohort of study were patients undergoing treatment with deep-inspiration breath-hold (DIBH), stratified by internal mammary nodes (IMN) inclusion. In all cases, the median (25th-75th percentile) is reported. RESULTS: A total of 1221 left-sided breast cancer patients were included in this study with 1045 in the DIBH cohort. The median heart mean dose for this cohort is 1.0 Gy (0.8-1.1). For patients treated in DIBH with IMNs included (n = 422), the median of the mean LAD dose is 3.6 Gy (2.9-4.4) and, for patients treated in DIBH with IMNs excluded (n = 623), the median of the mean LAD dose is 3.2 Gy (2.5-3.8). CONCLUSIONS: Appropriate respiratory management can be utilized to achieve low dose to the LAD for the majority of patients without compromising target coverage.

Results of the ACCEL trial: Dosimetry in accelerated partial breast irradiation.

PURPOSE: To report the achieved dosimetry in the ACCEL trial and compare the results to reported dosimetry from the major accelerated partial breast irradiation (APBI) phase III trials. METHODS: The ACCEL trial was a single arm, phase II, prospective cohort study. A five-field, inverse-planned, IMRT strategy was employed using a class solution technique to increase planning consistency including high dose conformity and low normal tissue dose to the ipsilateral breast. RESULTS: Between 2016 and 2019, 283 patients were treated with 27 Gy in five fractions in consecutive days. The average PTV conformity index was 1.1. For the ipsilateral breast, the median (range) volume receiving 95% and 50% of the prescription dose was 9.7% (3.2-22.4) and 30.3% (11.1-54.6), respectively. Compared to major APBI phase III trial constraints, this reduction in irradiated volume at the 95% and 50% isodose levels represents a reduction of 209 cm3 and 265 cm3, respectively. CONCLUSION: The IMRT planning strategy employed in the ACCEL trial demonstrated consistent and superior dosimetry by comparison to conventionally used 3D CRT techniques. Future APBI trials should update dosimetric constraints.

Quality of life after breast-conserving therapy and adjuvant radiotherapy for non-low-risk ductal carcinoma in situ (BIG 3-07/TROG 07.01): 2-year results of a randomised, controlled, phase 3 trial.

BACKGROUND: BIG 3-07/TROG 07.01 is an international, multicentre, randomised, controlled, phase 3 trial evaluating tumour bed boost and hypofractionation in patients with non-low-risk ductal carcinoma in situ following breast-conserving surgery and whole breast radiotherapy. Here, we report the effects of diagnosis and treatment on health-related quality of life (HRQOL) at 2 years. METHODS: The BIG 3-07/TROG 07.01 trial is ongoing at 118 hospitals in 11 countries. Women aged 18 years or older with completely excised non-low-risk ductal carcinoma in situ were randomly assigned, by use of a minimisation algorithm, to tumour bed boost or no tumour bed boost, following conventional whole breast radiotherapy or hypofractionated whole breast radiotherapy using one of three randomisation categories. Category A was a 4-arm randomisation of tumour bed boost versus no boost following conventional whole breast radiotherapy (50 Gy in 25 fractions over 5 weeks) versus hypofractionated whole breast radiotherapy (42·5 Gy in 16 fractions over 3·5 weeks). Category B was a 2-arm randomisation between tumour bed boost versus no boost following conventional whole breast radiotherapy, and category C was a 2-arm randomisation between tumour bed boost versus no boost following hypofractionated whole breast radiotherapy. Stratification factors were age at diagnosis, planned endocrine therapy, and treating centre. The primary endpoint, time to local recurrence, will be reported when participants have completed 5 years of follow-up. The HRQOL statistical analysis plan prespecified eight aspects of HRQOL, assessed by four questionnaires at baseline, end of treatment, and at 6, 12, and 24 months after radiotherapy: fatigue and physical functioning (EORTC QLQ-C30); cosmetic status, breast-specific symptoms, arm and shoulder functional status (Breast Cancer Treatment Outcome Scale); body image and sexuality (Body Image Scale); and perceived risk of invasive breast cancer (Cancer Worry Scale and a study-specific question). For each of these measures, tumour bed boost was compared with no boost, and conventional whole breast radiotherapy compared with hypofractionated whole breast radiotherapy, by use of generalised estimating equation models. Analyses were by intention to treat, with Hochberg adjustment for multiple testing. This trial is registered with ClinicalTrials.gov, NCT00470236. FINDINGS: Between June 1, 2007, and Aug 14, 2013, 1208 women were enrolled and randomly assigned to receive no tumour bed boost (n=605) or tumour bed boost (n=603). 396 of 1208 women were assigned to category A: conventional whole breast radiotherapy with tumour bed boost (n=100) or no boost (n=98), or to hypofractionated whole breast radiotherapy with tumour bed boost (n=98) or no boost (n=100). 447 were assigned to category B: conventional whole breast radiotherapy with tumour bed boost (n=223) or no boost (n=224). 365 were assigned to category C: hypofractionated whole breast radiotherapy with tumour bed boost (n=182) or no boost (n=183). All patients were followed up at 2 years for the HRQOL analysis. 1098 (91%) of 1208 patients received their allocated treatment, and most completed their scheduled HRQOL assessments (1147 [95%] of 1208 at baseline; 988 [87%] of 1141 at 2 years). Cosmetic status was worse with tumour bed boost than with no boost across all timepoints (difference 0·10 [95% CI 0·05-0·15], global p=0·00014, Hochberg-adjusted p=0·0016); at the end of treatment, the estimated difference between tumour bed boost and no boost was 0·13 (95% CI 0·06-0·20; p=0·00021), persisting at 24 months (0·13 [0·06-0·20]; p=0·00021). Arm and shoulder function was also adversely affected by tumour bed boost across all timepoints (0·08 [95% CI 0·03-0·13], global p=0·0033, Hochberg adjusted p=0·045); the difference between tumour bed boost and no boost at the end of treatment was 0·08 (0·01 to 0·15, p=0·021), and did not persist at 24 months (0·04 [-0·03 to 0·11], p=0·29). None of the other six prespecified aspects of HRQOL differed significantly after adjustment for multiple testing. Conventional whole breast radiotherapy was associated with worse body image than hypofractionated whole breast radiotherapy at the end of treatment (difference -1·10 [95% CI -1·79 to -0·42], p=0·0016). No significant differences were reported in the other PROs between conventional whole breast radiotherapy compared with hypofractionated whole breast radiotherapy. INTERPRETATION: Tumour bed boost was associated with persistent adverse effects on cosmetic status and arm and shoulder functional status, which might inform shared decision making while local recurrence analysis is pending. FUNDING: National Health and Medical Research Council, Susan G Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society.

International comparison of cosmetic outcomes of breast conserving surgery and radiation therapy for women with ductal carcinoma in situ of the breast.

PURPOSE: To assess the cosmetic impact of breast conserving surgery (BCS), whole breast irradiation (WBI) fractionation and tumour bed boost (TBB) use in a phase III trial for women with ductal carcinoma in situ (DCIS) of the breast. MATERIALS AND METHODS: Baseline and 3-year cosmesis were assessed using the European Organization for Research and Treatment of Cancer (EORTC) Cosmetic Rating System and digital images in a randomised trial of non-low risk DCIS treated with postoperative WBI +/- TBB. Baseline cosmesis was assessed for four geographic clusters of treating centres. Cosmetic failure was a global score of fair or poor. Cosmetic deterioration was a score change from excellent or good at baseline to fair or poor at three years. Odds ratios for cosmetic deterioration by WBI dose-fractionation and TBB use were calculated for both scoring systems. RESULTS: 1608 women were enrolled from 11 countries between 2007 and 2014. 85-90% had excellent or good baseline cosmesis independent of geography or assessment method. TBB (16 Gy in 8 fractions) was associated with a >2-fold risk of cosmetic deterioration (p < 0.001). Hypofractionated WBI (42.5 Gy in 16 fractions) achieved statistically similar 3-year cosmesis compared to conventional WBI (50 Gy in 25 fractions) (p ≥ 0.18). The adverse impact of a TBB was not significantly associated with WBI fractionation (interaction p ≥ 0.30). CONCLUSIONS: Cosmetic failure from BCS was similar across international jurisdictions. A TBB of 16 Gy increased the rate of cosmetic deterioration. Hypofractionated WBI achieved similar 3-year cosmesis as conventional WBI in women treated with BCS for DCIS.

External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node-negative breast cancer (RAPID): a randomised controlled trial.

BACKGROUND: Whole breast irradiation delivered once per day over 3-5 weeks after breast conserving surgery reduces local recurrence with good cosmetic results. Accelerated partial breast irradiation (APBI) delivered over 1 week to the tumour bed was developed to provide a more convenient treatment. In this trial, we investigated if external beam APBI was non-inferior to whole breast irradiation. METHODS: We did this multicentre, randomised, non-inferiority trial in 33 cancer centres in Canada, Australia and New Zealand. Women aged 40 years or older with ductal carcinoma in situ or node-negative breast cancer treated by breast conserving surgery were randomly assigned (1:1) to receive either external beam APBI (38·5 Gy in ten fractions delivered twice per day over 5-8 days) or whole breast irradiation (42·5 Gy in 16 fractions once per day over 21 days, or 50 Gy in 25 fractions once per day over 35 days). Patients and clinicans were not masked to treatment assignment. The primary outcome was ipsilateral breast tumour recurrence (IBTR), analysed by intention to treat. The trial was designed on the basis of an expected 5 year IBTR rate of 1·5% in the whole breast irradiation group with 85% power to exclude a 1·5% increase in the APBI group; non-inferiority was shown if the upper limit of the two-sided 90% CI for the IBTR hazard ratio (HR) was less than 2·02. This trial is registered with ClinicalTrials.gov, NCT00282035. FINDINGS: Between Feb 7, 2006, and July 15, 2011, we enrolled 2135 women. 1070 were randomly assigned to receive APBI and 1065 were assigned to receive whole breast irradiation. Six patients in the APBI group withdrew before treatment, four more did not receive radiotherapy, and 16 patients received whole breast irradiation. In the whole breast irradiation group, 16 patients withdrew, and two more did not receive radiotherapy. In the APBI group, a further 14 patients were lost to follow-up and nine patients withdrew during the follow-up period. In the whole breast irradiation group, 20 patients were lost to follow-up and 35 withdrew during follow-up. Median follow-up was 8·6 years (IQR 7·3-9·9). The 8-year cumulative rates of IBTR were 3·0% (95% CI 1·9-4·0) in the APBI group and 2·8% (1·8-3·9) in the whole breast irradiation group. The HR for APBI versus whole breast radiation was 1·27 (90% CI 0·84-1·91). Acute radiation toxicity (grade ≥2, within 3 months of radiotherapy start) occurred less frequently in patients treated with APBI (300 [28%] of 1070 patients) than whole breast irradiation (484 [45%] of 1065 patients, p<0·0001). Late radiation toxicity (grade ≥2, later than 3 months) was more common in patients treated with APBI (346 [32%] of 1070 patients) than whole breast irradiation (142 [13%] of 1065 patients; p<0·0001). Adverse cosmesis (defined as fair or poor) was more common in patients treated with APBI than in those treated by whole breast irradiation at 3 years (absolute difference, 11·3%, 95% CI 7·5-15·0), 5 years (16·5%, 12·5-20·4), and 7 years (17·7%, 12·9-22·3). INTERPRETATION: External beam APBI was non-inferior to whole breast irradiation in preventing IBTR. Although less acute toxicity was observed, the regimen used was associated with an increase in moderate late toxicity and adverse cosmesis, which might be related to the twice per day treatment. Other approaches, such as treatment once per day, might not adversely affect cosmesis and should be studied. FUNDING: Canadian Institutes for Health Research and Canadian Breast Cancer Research Alliance.

A Framework for Clinical Validation of Automatic Contour Propagation: Standardizing Geometric and Dosimetric Evaluation.

PURPOSE: The objective of this work was to outline and demonstrate a standardized framework for evaluating automatically propagated contour quality against expert contours. A 2-pronged approach is used to evaluate contour quality: a geometric evaluation to identify geometric and spatial discrepancies between propagated and expert contours, and a comprehensive dosimetric comparison to provide clinical context for the results. METHODS AND MATERIALS: The standardized framework requires a primary image, with reference contours and a radiation therapy treatment plan, and a secondary image. Reference contours are automatically propagated onto the secondary image anatomy and compared with expert contours obtained in an interobserver study. The standardized framework outlines geometric and dosimetric evaluation methodologies for determining indistinguishability between propagated and expert contours in a cohort analysis. Propagated contours are geometrically compared with expert contours in terms of the Dice similarity coefficient and the mean distance to agreement. Statistical analysis is performed on the central tendency and variability of Dice similarity coefficient and mean distance to agreement values over the patient cohort. Dosimetric evaluation involves computing the mean and 95% confidence intervals for the differences in cumulative dose-volume histograms for propagated and expert contours. A case study in accelerated partial breast irradiation was shown to demonstrate the framework. RESULTS: The standardized framework was applied to a case study of 24 patient data sets with 3 radiation oncologists providing the expert contours. Cohort analysis indicated that propagated contours were geometrically indistinguishable and dosimetrically distinguishable from expert contours. CONCLUSIONS: The recommended framework standardizes the comparison of geometric and dosimetric parameters to demonstrate indistinguishability of propagated contours from expert contours. Adoption of this framework is vital for consistent and comprehensive validation of automatic contour propagation for use in large-scale cohort analyses.

One-Year Cosmesis and Fibrosis From ACCEL: Accelerated Partial Breast Irradiation (APBI) Using 27 Gy in 5 Daily Fractions.

PURPOSE: To report 1-year cosmesis and toxicity outcomes of a prospective, phase II trial of accelerated partial breast irradiation using intensity-modulated radiation therapy (RT) to deliver 27 Gy in 5 daily fractions. METHODS AND MATERIALS: Node-negative breast cancer patients after breast conserving surgery with clear excision margins, with physician-assessed excellent or good baseline cosmesis were invited to participate in a prospective clinical trial to receive 27 Gy in 5 daily fractions to the expanded primary site. Clinical photographs and European Organisation for Research and Treatment of Cancer cosmetic score were collected at baseline prior to RT and 1-year after radiation therapy. A protocol-specified, interim analysis was scheduled when 50 patients had completed 1-year follow-up. A panel of 6 physicians provided a consensus global cosmetic score (termed panel-assessed score) based on clinical photographs at baseline and 1-year. Fibrosis and telangiectasia were prospectively assessed by clinical research staff at clinic visits. RESULTS: At the interim analysis, 55 patients had baseline and 1-year post-RT images available. Most patients had either an improvement (53%) or no change (40%) in cosmesis from baseline to 1-year. Among 49 patients with excellent or good panel-assessed score at baseline, only 2 (4%) patients had a fair score at 1-year post-RT, indicating cosmetic deterioration. No patients had evidence of telangiectasia or grade 2 or higher fibrosis. There were no recurrences. CONCLUSIONS: APBI using 27 Gy in 5 daily fractions achieved acceptable 1-year cosmesis and no grade 2 fibrosis. A preplanned stopping rule of 5% grade 2+ fibrosis was not observed. The trial will continue to the planned target accrual of 274 patients.

'Driving' Rates Down: A Population-Based Study of Opening New Radiation Therapy Centers on the Use of Mastectomy for Breast Cancer.

BACKGROUND: Two new cancer centers providing radiation therapy opened in Alberta, Canada, in 2010 and 2013, respectively. We aimed to assess whether opening the new RT centers influenced mastectomy rates for breast cancer. METHOD: Breast cancer patients who underwent surgery from 2004 through 2015 were identified from the Alberta Cancer Registry. Mastectomy rates for 64 predefined health status areas (HSAs) were calculated after adjusting for patient and system factors. Variations in mastectomy rates among the HSAs were quantified using weighted coefficient of variation (CV). Multivariable logistic regressions were performed to determine associations between driving time and mastectomy use in the entire cohort and in subgroups. RESULTS: Of the 21,872 patients, the proportion of patients who lived a ≤ 60 min drive from the nearest RT center significantly increased from 68.8% (95% CI 67.7-69.9%) to 80.7% (95% CI 79.5-81.9%) during the study period. Concurrently, the crude provincial mastectomy rate decreased from 56.2% (95% CI 55.3-57.1%) to 45.3% (95% CI 44.1-46.5%). However, variation in adjusted mastectomy rates (weighted CV) across the 64 HSAs increased from 9.5 to 14.6. Factors associated with mastectomy included age, larger tumor size, lymph node involvement, higher tumor grade, molecular subtype, lobular histology type, more comorbidities, academic institution, region, earlier period of diagnosis, and longer driving time to the nearest RT center. CONCLUSIONS: Opening new RT centers in previously underserved regions reduced driving times to the nearest center, and was associated with a reduction in mastectomy rates; however, these reductions among regions across the province were not uniform.

Clinical implementation of AXB from AAA for breast: Plan quality and subvolume analysis.

PURPOSE: Two dose calculation algorithms are available in Varian Eclipse software: Anisotropic Analytical Algorithm (AAA) and Acuros External Beam (AXB). Many Varian Eclipse-based centers have access to AXB; however, a thorough understanding of how it will affect plan characteristics and, subsequently, clinical practice is necessary prior to implementation. We characterized the difference in breast plan quality between AXB and AAA for dissemination to clinicians during implementation. METHODS: Locoregional irradiation plans were created with AAA for 30 breast cancer patients with a prescription dose of 50 Gy to the breast and 45 Gy to the regional node, in 25 fractions. The internal mammary chain (IMCCTV ) nodes were covered by 80% of the breast dose. AXB, both dose-to-water and dose-to-medium reporting, was used to recalculate plans while maintaining constant monitor units. Target coverage and organ-at-risk doses were compared between the two algorithms using dose-volume parameters. An analysis to assess location-specific changes was performed by dividing the breast into nine subvolumes in the superior-inferior and left-right directions. RESULTS: There were minimal differences found between the AXB and AAA calculated plans. The median difference between AXB and AAA for breastCTV V95% , was <2.5%. For IMCCTV , the median differences V95% , and V80% were <5% and 0%, respectively; indicating IMCCTV coverage only decreased when marginally covered. Mean superficial dose increased by a median of 3.2 Gy. In the subvolume analysis, the medial subvolumes were "hotter" when recalculated with AXB and the lateral subvolumes "cooler" with AXB; however, all differences were within 2 Gy. CONCLUSION: We observed minimal difference in magnitude and spatial distribution of dose when comparing the two algorithms. The largest observable differences occurred in superficial dose regions. Therefore, clinical implementation of AXB from AAA for breast radiotherapy is not expected to result in changes in clinical practice for prescribing or planning breast radiotherapy.

Deep inspiration breath hold level variability and deformation in locoregional breast irradiation.

PURPOSE: The purpose of this study was to evaluate the dosimetric effect of breath hold level variability and deformation on breast, chest wall, internal mammary chain (IMC) nodes, and heart. METHODS AND MATERIALS: Left-sided post-lumpectomy (n = 12) and postmastectomy (n = 3) patients underwent deep inspiration breath hold (DIBH) and exhale breath hold (EBH) computed tomography (CT) scans. Forward-planned locoregional breast plans were created on the DIBH scan. Two effects were modeled assuming no setup uncertainties: residual motion within the gating window and systematically shallow breath hold levels (BHLs). Real-time position management (RPM) was used to monitor BHL at simulation and during treatment. The RPM data were scaled to simulate BHL variation within symmetric gating window widths of ±1, 3, 5, and 7 mm; the dosimetric impact of this motion was simulated in the treatment planning system. Systematically "shallow" BHL errors were modeled using deformable image registration to map the patient trajectory from DIBH to EBH (n = 12). The deformable vector fields were scaled to produce synthetic CT scans modeling patient position during breath holds 1, 3, 5, and 7 mm shallower than simulator BHL. The original treatment plans were applied to the synthetic CTs and dose was recalculated. RESULTS: Acceptable plan quality was maintained for most patients with motion within gating windows up to ±7 mm. Patients with shallow median BHLs experienced loss of coverage at simulated gating windows ±5 mm or larger. At systematic 3 mm shallow BHL error, 4/12 patients had clinical target volume IMC V80% < 99%; this increased to 11/12 patients at 5 mm. Change in heart dose from systematic BHL errors was negligible. CONCLUSIONS: Motion within gating windows has minimal dosimetric impact for most BHL variability; however, loss of IMC coverage can occur even for small gating windows when BHLs are systematically shallow. This can be mitigated by restricting lower BHL tolerances or accounting for known uncertainties in planning.

What Conditions Make Proton Beam Therapy Financially Viable in Western Canada?

Background Proton beam therapy (PBT) is available in many western and Asian countries, but there is no clinical, gantry-based PBT facility in Canada. Methods A cost analysis was conducted from the Alberta Ministry of Health perspective with a 15-year horizon. Estimated costs were: PBT unit, facility development as part of an ongoing capital project, electricity, maintenance contract, and staffing. Revenues were: savings from stopping USA referrals, avoiding the costs of standard radiation therapy (RT) for Albertans receiving PBT instead, and cost-recovery charges for out-of-province patients. Results The Ministry of Health funded 15 Albertans for PBT in the USA in the 2014/15 fiscal year (mean CAD$ 237,348/patient). A single-vault, compact PBT unit operating 10 hours/day could treat 250 patients annually. A 100 Albertans, with accepted indications, such as the curative-intent treatment of chordomas, ocular melanomas, and selected pediatric cancers, would likely benefit annually from PBT's improved conformality and/or reduced integral dose compared to RT. The estimated capital cost was $40 million for a single beamline built within an ongoing capital project. Operating costs were $4.8 million/year at capacity. With 50% capacity reserved for non-Albertans at a cost recovery of $45,000/patient, a Western Canadian PBT facility would achieve net positive cash flow by year eight of clinical operations, assuming Alberta-to-USA referrals reach 21 patients/year by 2024 and increase at 3%/year thereafter. Sensitivity analysis indicates the lifetime net savings is robust to the assumptions made. Conclusion This business case, based on Canadian costing data and estimates, demonstrates the potential for a financially viable PBT facility in Western Canada.

Systemic Lupus Erythematosus is Not Necessarily a Contraindication to Adjuvant Breast Radiation Therapy.

A 41-year-old woman presented with pT4dN1aM0, right-sided, inflammatory breast cancer. She had a co-morbid diagnosis of systemic lupus erythematosus (SLE) at the age of 20 and was found to have significant kidney involvement (lupus-associated nephritis) at the age of 28. She went on to receive six cycles of neoadjuvant chemotherapy consisting of fluorouracil, epirubicin, cyclophosphamide, and docetaxcel (FEC-D) after which she had radiographically stable disease. She then had definitive treatment with bilateral mastectomy. Pathology showed a 4-cm residual invasive ductal carcinoma in the right breast and three residual metastatic lymph nodes in the right axilla. After extensive discussions with the patient, which included counseling on the potential increased risk of radiation-induced side effects, she received 50.4 Gy in 28 fractions of adjuvant radiotherapy (RT) to the chest wall and regional lymphatics including the internal mammary chains (IMCs). To minimize the risk of pulmonary toxicity, RT field arrangement consisted of a field-in-field modulated supraclavicular anterior/posterior parallel pair matched to shallow, photon tangent pair with 0.5 cm bolus to the lateral aspect of the chest wall and two matched direct anterior electron fields of 9 MeV with 1 cm bolus and 12 MeV with 0.5 cm bolus medially to cover the remaining residual chest wall and IMCs. This was immediately followed by a boost of 7.5 Gy in three fractions delivered via a photon tangent pair with 1 cm bolus to an area 6 cm superior and inferior to the surgical scar. Total treatment time was 50 days. The patient tolerated the therapy well but she developed grade three acute dermatitis. There were no pulmonary, shoulder joint movement, or brachial plexus side effects. This case is unusual in that SLE is generally considered a contraindication for elective RT. However, given her high risk for breast cancer recurrence, RT was offered with additional caution to minimize lung dose. Having completed the treatment, the side effects experienced were no greater than what would be expected in someone who did not have a diagnosis of SLE.

Signed family physician reminder letters to women overdue for screening mammography: A randomized clinical trial.

OBJECTIVE: To determine whether signed family physician reminder letters to women overdue for screening mammography prompts rescreening. METHODS: A randomized double-blind trial conducted in 2013 among women aged 51-73 and overdue for screening by 6-24 months. The study was carried out by the publicly funded British Columbia Cancer Agency Screening Mammography Program, which routinely sends standard reminder postcards to women who are due for mammography. Participating family physicians signed letters for the overdue women in their practices. The overdue women were mailed either the signed reminder letter and the standard reminder postcard, or the standard reminder postcard alone. The primary endpoint was the proportion of overdue women that attended a screening mammogram appointment within six months of mailing the study letters. The analysis was by intention to treat. RESULTS: In total, 822 family physicians participated and 5638 women were randomized. Mammography attendance by six months after mailing the reminders was 34.4% (947/2749) for women in the signed family physician letter arm, compared with 24.0% (660/2749) for women in the control arm (p < 0.0001). Adjusting for age, number of previous screening mammograms, and months overdue, women in the signed letter arm were significantly more likely to return for screening than women in the control arm (RR 1.41; 95% confidence interval: 1.30-1.54). CONCLUSION: A signed family physician reminder letter improved mammography attendance for women who were overdue for screening mammography.

Hypofractionated Nodal Radiation Therapy for Breast Cancer Was Not Associated With Increased Patient-Reported Arm or Brachial Plexopathy Symptoms.

PURPOSE: To determine whether nodal radiation therapy (RT) for breast cancer using modest hypofractionation (HF) with 2.25 to 2.5 Gy per fraction (fx) was associated with increased patient-reported arm symptoms, compared with conventional fractionation (CF) ≤2 Gy/fx. METHODS AND MATERIALS: Two cancer registries were used to identify subjects who received computed tomography-planned nodal RT for pT1-3, pN0-2, M0 breast cancer, from 2007 to 2010 at 2 cancer institutions. After ethics approval, patients were mailed an explanatory letter and the Self-reported Arm Symptom Scale, a validated instrument with 8 questions about arm symptoms and 5 related to activities of daily living. Clinicopathologic characteristics and Self-reported Arm Symptom Scale scores were compared between HF/CF cohorts using nonparametric analysis, χ2 analysis, and multivariate ordinal regression. RESULTS: Of 1759 patients, 800 (45.5%) returned a completed survey. A total of 708 eligible cases formed the study cohort. Of these, 406 (57%) received HFRT (40 Gy/16 fx, 45 Gy/20 fx), and 302 (43%) received CFRT (45-50 Gy/25 fx, 50.4 Gy/28 fx). Median time interval after RT was 5.7 years. Forty-three percent and 75% of patients received breast-conserving surgery and chemotherapy, respectively. Twenty-two percent received breast boost RT, independent of fractionation. Median age at diagnosis was 59 years (HF) and 53 years (CF) (P<.001). The mean numbers of excised (n=12) and involved (n=3) nodes were similar between fractionation cohorts (P=.44), as were the mean sums of responses in arm symptoms (P=.17) and activities of daily living (P=.85). Patients receiving HF reported lower rates of shoulder stiffness (P=.04), trouble moving the arm (P=.02), and difficulty reaching overhead (P<.01) compared with the CF cohort. There was no difference in self-reported arm swelling or symptoms related to brachial plexopathy. CONCLUSIONS: Nodal RT with hypofractionation was not associated with increased patient-reported arm symptoms or functional deficits compared with CF. Subjects treated with CF reported more disability in certain aspects of arm/shoulder function. These data support shorter fractionation utilization when regional nodes are within the therapeutic target.

Radiation therapy quality indicators for invasive breast cancer.

BACKGROUND AND PURPOSE: Radiation therapy (RT) for breast cancer has evolved considerably over the past two decades. A concise list of optimal care indexes is lacking. The purpose of this project was to generate a suite of quality of care indicators for breast cancer RT. MATERIALS AND METHODS: A modified Delphi approach was used including a comprehensive literature and guideline review (1995-2015), an initial review of potential quality indicators (QIs) by a steering committee, a survey of Canadian Radiation Oncologists, and a face-to-face consensus development meeting with breast cancer experts to develop a list of breast RT quality indicators. RESULTS: The literature review identified 163 potential QIs, which was reduced to 73 by the steering committee. After all rounds of the Delphi process the final suite included 33 QIs. Of these, 28 (85%) received at least 80% acceptance from the Radiation Oncologists who participated in the final online survey. CONCLUSIONS: A suite of measureable RT quality indicators to be considered during management of invasive breast cancer was developed. These indicators could be used to assess the quality and consistency of breast cancer RT practices.

Deep inspiration breath-hold produces a clinically meaningful reduction in ipsilateral lung dose during locoregional radiation therapy for some women with right-sided breast cancer.

PURPOSE: The goal of the work described here was to determine whether deep inspiration breath-hold (DIBH) produces a clinically meaningful reduction in pulmonary dose compared with free breathing (FB) during locoregional radiation for right-sided breast cancer. METHODS AND MATERIALS: Four-field, modified-wide tangent plans with full nodal coverage were developed for 30 consecutive patients on paired DIBH and FB CT scans. Nodes were contoured according to European Society for Radiotherapy and Oncology guidelines. Plan metrics were compared using Wilcoxon signed-rank testing. RESULTS: In 21 patients (70%), there was a ≥5% reduction in ipsilateral lung V20Gy with DIBH compared with FB. The mean decrease in ipsilateral lung V20Gy was 7.8% (0%-20%, P < .001). The mean lung dose decreased on average by 3.4 Gy with DIBH (-0.2 to 9.1, P < .001). The mean reduction in liver volume receiving 50% of the prescribed dose was 42.3 cm3 (0-178.9 cm3, P < .001). CONCLUSIONS: DIBH reduced ipsilateral lung V20Gy by ≥5% in the majority of patients. For some patients, the volume of liver receiving a potentially toxic dose decreased with DIBH. DIBH should be available as a treatment strategy to reduce ipsilateral lung V20Gy prior to compromising internal mammary chain nodal coverage for patients with right-sided breast cancer during locoregional radiation therapy if the V20Gy on FB exceeds 30%.