The American Society of Radiation Oncology has recently updated its guidelines on the role of accelerated partial breast irradiation in the management of breast cancer. This commentary discusses the ...new recommendations and how we might advise patients in the light of existing data.
We aimed to identify a five-fraction schedule of adjuvant radiotherapy (radiation therapy) delivered in 1 week that is non-inferior in terms of local cancer control and is as safe as an international ...standard 15-fraction regimen after primary surgery for early breast cancer. Here, we present 5-year results of the FAST-Forward trial.
FAST-Forward is a multicentre, phase 3, randomised, non-inferiority trial done at 97 hospitals (47 radiotherapy centres and 50 referring hospitals) in the UK. Patients aged at least 18 years with invasive carcinoma of the breast (pT1–3, pN0–1, M0) after breast conservation surgery or mastectomy were eligible. We randomly allocated patients to either 40 Gy in 15 fractions (over 3 weeks), 27 Gy in five fractions (over 1 week), or 26 Gy in five fractions (over 1 week) to the whole breast or chest wall. Allocation was not masked because of the nature of the intervention. The primary endpoint was ipsilateral breast tumour relapse; assuming a 2% 5-year incidence for 40 Gy, non-inferiority was predefined as ≤1·6% excess for five-fraction schedules (critical hazard ratio HR of 1·81). Normal tissue effects were assessed by clinicians, patients, and from photographs. This trial is registered at isrctn.com, ISRCTN19906132.
Between Nov 24, 2011, and June 19, 2014, we recruited and obtained consent from 4096 patients from 97 UK centres, of whom 1361 were assigned to the 40 Gy schedule, 1367 to the 27 Gy schedule, and 1368 to the 26 Gy schedule. At a median follow-up of 71·5 months (IQR 71·3 to 71·7), the primary endpoint event occurred in 79 patients (31 in the 40 Gy group, 27 in the 27 Gy group, and 21 in the 26 Gy group); HRs versus 40 Gy in 15 fractions were 0·86 (95% CI 0·51 to 1·44) for 27 Gy in five fractions and 0·67 (0·38 to 1·16) for 26 Gy in five fractions. 5-year incidence of ipsilateral breast tumour relapse after 40 Gy was 2·1% (1·4 to 3·1); estimated absolute differences versus 40 Gy in 15 fractions were −0·3% (−1·0 to 0·9) for 27 Gy in five fractions (probability of incorrectly accepting an inferior five-fraction schedule: p=0·0022 vs 40 Gy in 15 fractions) and −0·7% (−1·3 to 0·3) for 26 Gy in five fractions (p=0·00019 vs 40 Gy in 15 fractions). At 5 years, any moderate or marked clinician-assessed normal tissue effects in the breast or chest wall was reported for 98 of 986 (9·9%) 40 Gy patients, 155 (15·4%) of 1005 27 Gy patients, and 121 of 1020 (11·9%) 26 Gy patients. Across all clinician assessments from 1–5 years, odds ratios versus 40 Gy in 15 fractions were 1·55 (95% CI 1·32 to 1·83, p<0·0001) for 27 Gy in five fractions and 1·12 (0·94 to 1·34, p=0·20) for 26 Gy in five fractions. Patient and photographic assessments showed higher normal tissue effect risk for 27 Gy versus 40 Gy but not for 26 Gy versus 40 Gy.
26 Gy in five fractions over 1 week is non-inferior to the standard of 40 Gy in 15 fractions over 3 weeks for local tumour control, and is as safe in terms of normal tissue effects up to 5 years for patients prescribed adjuvant local radiotherapy after primary surgery for early-stage breast cancer.
National Institute for Health Research Health Technology Assessment Programme.
Local cancer relapse risk after breast conservation surgery followed by radiotherapy has fallen sharply in many countries, and is influenced by patient age and clinicopathological factors. We ...hypothesise that partial-breast radiotherapy restricted to the vicinity of the original tumour in women at lower than average risk of local relapse will improve the balance of beneficial versus adverse effects compared with whole-breast radiotherapy.
IMPORT LOW is a multicentre, randomised, controlled, phase 3, non-inferiority trial done in 30 radiotherapy centres in the UK. Women aged 50 years or older who had undergone breast-conserving surgery for unifocal invasive ductal adenocarcinoma of grade 1–3, with a tumour size of 3 cm or less (pT1–2), none to three positive axillary nodes (pN0–1), and minimum microscopic margins of non-cancerous tissue of 2 mm or more, were recruited. Patients were randomly assigned (1:1:1) to receive 40 Gy whole-breast radiotherapy (control), 36 Gy whole-breast radiotherapy and 40 Gy to the partial breast (reduced-dose group), or 40 Gy to the partial breast only (partial-breast group) in 15 daily treatment fractions. Computer-generated random permuted blocks (mixed sizes of six and nine) were used to assign patients to groups, stratifying patients by radiotherapy treatment centre. Patients and clinicians were not masked to treatment allocation. Field-in-field intensity-modulated radiotherapy was delivered using standard tangential beams that were simply reduced in length for the partial-breast group. The primary endpoint was ipsilateral local relapse (80% power to exclude a 2·5% increase non-inferiority margin at 5 years for each experimental group; non-inferiority was shown if the upper limit of the two-sided 95% CI for the local relapse hazard ratio HR was less than 2·03), analysed by intention to treat. Safety analyses were done in all patients for whom data was available (ie, a modified intention-to-treat population). This study is registered in the ISRCTN registry, number ISRCTN12852634.
Between May 3, 2007, and Oct 5, 2010, 2018 women were recruited. Two women withdrew consent for use of their data in the analysis. 674 patients were analysed in the whole-breast radiotherapy (control) group, 673 in the reduced-dose group, and 669 in the partial-breast group. Median follow-up was 72·2 months (IQR 61·7–83·2), and 5-year estimates of local relapse cumulative incidence were 1·1% (95% CI 0·5–2·3) of patients in the control group, 0·2% (0·02–1·2) in the reduced-dose group, and 0·5% (0·2–1·4) in the partial-breast group. Estimated 5-year absolute differences in local relapse compared with the control group were −0·73% (−0·99 to 0·22) for the reduced-dose and −0·38% (−0·84 to 0·90) for the partial-breast groups. Non-inferiority can be claimed for both reduced-dose and partial-breast radiotherapy, and was confirmed by the test against the critical HR being more than 2·03 (p=0·003 for the reduced-dose group and p=0·016 for the partial-breast group, compared with the whole-breast radiotherapy group). Photographic, patient, and clinical assessments recorded similar adverse effects after reduced-dose or partial-breast radiotherapy, including two patient domains achieving statistically significantly lower adverse effects (change in breast appearance p=0·007 for partial-breast and breast harder or firmer p=0·002 for reduced-dose and p<0·0001 for partial-breast) compared with whole-breast radiotherapy.
We showed non-inferiority of partial-breast and reduced-dose radiotherapy compared with the standard whole-breast radiotherapy in terms of local relapse in a cohort of patients with early breast cancer, and equivalent or fewer late normal-tissue adverse effects were seen. This simple radiotherapy technique is implementable in radiotherapy centres worldwide.
Cancer Research UK.
...boost volumes should be small and targeted. ...it is necessary that patients are empowered to exercise choices that reflect their individual preferences. RJ is funded by the Susan G Komen ...Foundation and has received grants paid to her institution for unrelated work from the National Institutes of Health, the Doris Duke Foundation, the Greenwall Foundation, the American Cancer Society, and Blue Cross Blue Shield of Michigan for the Michigan Radiation Oncology Quality Consortium; was principal investigator on a contract to conduct an investigator-initiated study with Genentech on the financial toxicity experienced by patients with breast cancer, paid to her institution; received personal fees for an advisory or grant review service from the National Institutes of Health, the Doris Duke Foundation, and the Greenwall Foundation; served as an expert witness for Sherinian and Hasso, Dressman Benzinger LaVelle, and Kleinbard, unrelated to the topic of this Comment; and has stock options as compensation for her advisory board role in Equity Quotient, a company that evaluates culture in health-care companies unrelated to the topic of this Comment.
There were ten instances of ischaemic heart disease reported in IMPORT HIGH and confirmed by investigation; 8 and 2 from people with left-sided and right-sided breast cancer, respectively. Subgroup ...analysis by age was not planned because the event rate for local recurrence is very low, making these data unreliable, especially as there were only 322 participants younger than 40 years within our trial. CEC reports grants from the National Institute for Health Research Efficacy and Mechanism Evaluation, Cancer Research UK RadNet, the Lancet Breast Cancer Commission, and Addenbrooke's Charitable Trust outside the submitted work; reports membership of five external independent monitoring committees; is Chair of the Lancet Breast Cancer Commission; and is funded by the National Institute for Health and Care Research (NIHR) and supported by the NIHR Cambridge Biomedical Research Centre.
High-field magnetic resonance-linear accelerators (MR-Linacs), linear accelerators combined with a diagnostic magnetic resonance imaging (MRI) scanner and online adaptive workflow, potentially give ...rise to novel online anatomic and response adaptive radiation therapy paradigms. The first high-field (1.5T) MR-Linac received regulatory approval in late 2018, and little is known about clinical use, patient tolerability of daily high-field MRI, and toxicity of treatments. Herein we report the initial experience within the MOMENTUM Study (NCT04075305), a prospective international registry of the MR-Linac Consortium.
Patients were included between February 2019 and October 2020 at 7 institutions in 4 countries. We used descriptive statistics to describe the patterns of care, tolerability (the percentage of patients discontinuing their course early), and safety (grade 3-5 Common Terminology Criteria for Adverse Events v.5 acute toxicity within 3 months after the end of treatment).
A total 943 patients participated in the MOMENTUM Study, 702 of whom had complete baseline data at the time of this analysis. Patients were primarily male (79%) with a median age of 68 years (range, 22-93) and were treated for 39 different indications. The most frequent indications were prostate (40%), oligometastatic lymph node (17%), brain (12%), and rectal (10%) cancers. The median number of fractions was 5 (range, 1-35). Six patients discontinued MR-Linac treatments, but none due to an inability to tolerate repeated high-field MRI. Of the 415 patients with complete data on acute toxicity at 3-month follow-up, 18 (4%) patients experienced grade 3 acute toxicity related to radiation. No grade 4 or 5 acute toxicity related to radiation was observed.
In the first 21 months of our study, patterns of care were diverse with respect to clinical utilization, body sites, and radiation prescriptions. No patient discontinued treatment due to inability to tolerate daily high-field MRI scans, and the acute radiation toxicity experience was encouraging.
Abstract Purpose To compare non-target tissue (including left-anterior-descending coronary-artery (LAD)) dosimetry of prone versus supine whole (WBI) and partial-breast irradiation (PBI). Methods and ...materials Sixty-five post-lumpectomy breast cancer patients underwent CT-imaging supine and prone. On each dataset, the whole-breast clinical-target-volume (WB-CTV), partial-breast CTV (tumour-bed + 15 mm), ipsilateral-lung and chest-wall were outlined. Heart and LAD were outlined in left-sided cases ( n = 30). Tangential-field WBI and PBI plans were generated for each position. Mean LAD, heart, and ipsilateral-lung doses ( xmean ), maximum LAD (LADmax ) doses, and the volume of chest-wall receiving 50 Gy ( V50Gy ) were compared. Results Two-hundred and sixty plans were generated. Prone positioning reduced heart and LAD doses in 19/30 WBI cases (median reduction in LADmean = 6.2 Gy) and 7/30 PBI cases (median reduction in LADmax = 29.3 Gy) (no difference in 4/30 cases). However, prone positioning increased cardiac doses in 8/30 WBI (median increase in LADmean = 9.5 Gy) and 19/30 PBI cases (median increase in LADmax = 22.9 Gy) (no difference in 3/30 cases). WB-CTV > 1000cm3 was associated with improved cardiac dosimetry in the prone position for WBI ( p = 0.04) and PBI ( p = 0.04). Prone positioning reduced ipsilateral-lungmean in 65/65 WBI and 61/65 PBI cases, and chest-wall V50Gy in all WBI cases. PBI reduced normal-tissue doses compared to WBI in all cases, regardless of the treatment position. Conclusions In the context of tangential-field WBI and PBI, prone positioning is likely to benefit left-breast-affected women of larger breast volume, but to be detrimental in left-breast-affected women of smaller breast volume. Right-breast-affected women are likely to benefit from prone positioning regardless of breast volume.
To assess the pathologic and radiologic response in patients with low-risk breast cancer treated with magnetic resonance (MR) guided neoadjuvant partial breast irradiation (NA-PBI) and to evaluate ...toxicity and patient-reported outcomes (PROs).
For this single-arm prospective trial, women with unifocal, non-lobular tumors with a maximum diameter of 20 mm (age, 50-70 years) or 30 mm (age, ≥70 years) and tumor-negative sentinel node(s) were eligible. Patients were treated with a single ablative dose of NA-PBI followed by breast-conserving surgery after an interval of 6 to 8 months. Target volumes were defined on radiation therapy planning computed tomography scan and additional magnetic resonance imaging. Prescribed doses to gross tumor volume and clinical target volume (gross tumor volume plus 20 mm margin) were 20 Gy and 15 Gy, respectively. Primary outcome was pathologic complete response (pCR). Secondary outcomes were radiologic response (on magnetic resonance imaging), toxicity (Common Terminology Criteria for Adverse Events), PROs (European Organisation for Research and Treatment of Cancer QLQ-BR23, Hospital Anxiety and Depression Scale), and cosmesis (assessed by patient, radiation oncologist, and BCCT.core software).
Thirty-six patients were treated with NA-PBI, and pCR was reported in 15 patients (42%; 95% confidence interval, 26%-59%). Radiologic complete response was observed in 15 patients, 10 of whom had pCR (positive predictive value, 67%; 95% confidence interval, 39%-87%). After a median follow-up of 21 months (range, 12-41), all patients experienced grade 1 fibrosis in the treated breast volume. Transient grade 2 and 3 toxicity was observed in 31% and 3% of patients, respectively. Local recurrences were absent. No deterioration in PROs or cosmetic results was observed.
NA-PBI has the potential to induce pCR in a substantial proportion of patients, with acceptable toxicity. This treatment seems a feasible alternative to standard postoperative irradiation and could even result in postponement or omission of surgery if pCR can be accurately predicted in selected low-risk patients.
Abstract Purpose To determine whether voluntary deep-inspiratory breath-hold (v_DIBH) and deep-inspiratory breath-hold with the active breathing coordinator™ (ABC_DIBH) in patients undergoing left ...breast radiotherapy are comparable in terms of normal-tissue sparing, positional reproducibility and feasibility of delivery. Methods Following surgery for early breast cancer, patients underwent planning-CT scans in v_DIBH and ABC_DIBH. Patients were randomised to receive one technique for fractions 1–7 and the second technique for fractions 8–15 (40 Gy/15 fractions total). Daily electronic portal imaging (EPI) was performed and matched to digitally-reconstructed radiographs. Cone-beam CT (CBCT) images were acquired for 6/15 fractions and matched to planning-CT data. Population systematic ( Σ ) and random errors ( σ ) were estimated. Heart, left-anterior-descending coronary artery, and lung doses were calculated. Patient comfort, radiographer satisfaction and scanning/treatment times were recorded. Within-patient comparisons between the two techniques used the paired t -test or Wilcoxon signed-rank test. Results Twenty-three patients were recruited. All completed treatment with both techniques. EPI-derived Σ were ⩽1.8 mm (v_DIBH) and ⩽2.0 mm (ABC_DIBH) and σ ⩽2.5 mm (v_DIBH) and ⩽2.2 mm (ABC_DIBH) (all p non-significant). CBCT-derived Σ were ⩽3.9 mm (v_DIBH) and ⩽4.9 mm (ABC_DIBH) and σ ⩽ 4.1 mm (v_DIBH) and ⩽ 3.8 mm (ABC_DIBH). There was no significant difference between techniques in terms of normal-tissue doses (all p non-significant). Patients and radiographers preferred v_DIBH ( p = 0.007, p = 0.03, respectively). Scanning/treatment setup times were shorter for v_DIBH ( p = 0.02, p = 0.04, respectively). Conclusions v_DIBH and ABC_DIBH are comparable in terms of positional reproducibility and normal tissue sparing. v_DIBH is preferred by patients and radiographers, takes less time to deliver, and is cheaper than ABC_DIBH.
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