Health-related quality of life of early-stage breast cancer patients after different radiotherapy regimens.

PURPOSE: To evaluate and compare health-related quality of life (HRQL) of women with early-stage breast cancer (BC) treated with different radiotherapy (RT) regimens. METHODS: Data were collected from five prospective cohorts of BC patients treated with breast-conserving surgery and different RT regimens: intraoperative RT (IORT, 1 × 23.3 Gy; n = 267), external beam accelerated partial breast irradiation (EB-APBI, 10 × 3.85 Gy; n = 206), hypofractionated whole breast irradiation(hypo-WBI, 16 × 2.67 Gy; n = 375), hypo-WBI + boost(hypo-WBI-B, 21-26 × 2.67 Gy; n = 189), and simultaneous WBI + boost(WBI-B, 28 × 2.3 Gy; n = 475). Women ≥ 60 years with invasive/in situ carcinoma ≤ 30 mm, cN0 and pN0-1a were included. Validated EORTC QLQ-C30/BR23 questionnaires were used to asses HRQL. Multivariable linear regression models adjusted for confounding (age, comorbidity, pT, locoregional treatment, systemic therapy) were used to compare the impact of the RT regimens on HRQL at 12 and 24 months. Differences in HRQL over time (3-24 months) were evaluated using linear mixed models. RESULTS: There were no significant differences in HRQL at 12 months between groups except for breast symptoms which were better after IORT and EB-APBI compared to hypo-WBI at 12 months (p < 0.001). Over time, breast symptoms, fatigue, global health status and role functioning were significantly better after IORT and EB-APBI than hypo-WBI. At 24 months, HRQL was comparable in all groups. CONCLUSION: In women with early-stage breast cancer, the radiotherapy regimen did not substantially influence long-term HRQL with the exception of breast symptoms. Breast symptoms are more common after WBI than after IORT or EB-APBI and improve slowly until no significant difference remains at 2 years posttreatment.

Dynamic Contrast-enhanced and Diffusion-weighted Magnetic Resonance Imaging for Response Evaluation After Single-Dose Ablative Neoadjuvant Partial Breast Irradiation.

Purpose: We aimed to evaluate changes in dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) magnetic resonance imaging (MRI) scans acquired before and after single-dose ablative neoadjuvant partial breast irradiation (NA-PBI), and explore the relation between semiquantitative MRI parameters and radiologic and pathologic responses. Methods and Materials: We analyzed 3.0T DCE and DW-MRI of 36 patients with low-risk breast cancer who were treated with single-dose NA-PBI, followed by breast-conserving surgery 6 or 8 months later. MRI was acquired before NA-PBI and 1 week, 2, 4, and 6 months after NA-PBI. Breast radiologists assessed the radiologic response and breast pathologists scored the pathologic response after surgery. Patients were grouped as either pathologic responders or nonresponders (<10% vs ≥10% residual tumor cells). The semiquantitative MRI parameters evaluated were time to enhancement (TTE), 1-minute relative enhancement (RE1min), percentage of enhancing voxels (%EV), distribution of washout curve types, and apparent diffusion coefficient (ADC). Results: In general, the enhancement increased 1 week after NA-PBI (baseline vs 1 week median - TTE: 15s vs 10s; RE1min: 161% vs 197%; %EV: 47% vs 67%) and decreased from 2 months onward (6 months median - TTE: 25s; RE1min: 86%; %EV: 12%). Median ADC increased from 0.83 × 10-3 mm2/s at baseline to 1.28 × 10-3 mm2/s at 6 months. TTE, RE1min, and %EV showed the most potential to differentiate between radiologic responses, and TTE, RE1min, and ADC between pathologic responses. Conclusions: Semiquantitative analyses of DCE and DW-MRI showed changes in relative enhancement and ADC 1 week after NA-PBI, indicating acute inflammation, followed by changes indicating tumor regression from 2 to 6 months after radiation therapy. A relation between the MRI parameters and radiologic and pathologic responses could not be proven in this exploratory study.

Tumor-Infiltrating Lymphocytes in Low-Risk Patients With Breast Cancer Treated With Single-Dose Preoperative Partial Breast Irradiation.

PURPOSE: Preoperative partial breast irradiation (PBI) has the potential to induce tumor regression. We evaluated the differences in the numbers of preirradiation tumor infiltrating lymphocytes (TILs) between responders and nonresponders after preoperative PBI in low-risk patients with breast cancer. Furthermore, we evaluated the change in number of TILs before and after irradiation. METHODS AND MATERIALS: In the prospective ABLATIVE study, low-risk patients with breast cancer underwent treatment with single-dose preoperative PBI (20 Gy) to the tumor and breast-conserving surgery after 6 or 8 months. In the preirradiation diagnostic biopsy and postirradiation resection specimen, numbers of TILs in 3 square regions of 450 × 450 µm were counted manually. TILs were visualized with CD3, CD4, and CD8 immunohistochemistry. Differences in numbers of preirradiation TILs between responders and nonresponders were tested using Mann-Whitney U test. Responders were defined as pathologic complete or near-complete response, and nonresponders were defined "as all other response." Changes in numbers of TILs after preoperative PBI was evaluated with the Wilcoxon signed rank test. RESULTS: Preirradiation tissue was available from 28 patients, postirradiation tissue from 29 patients, resulting in 22 pairs of preirradiation and postirradiation tissue. In these 35 patients, 15 had pathologic complete response (43%), 11 had a near-complete response (31%), 7 had a partial response (20%), and 2 had stable disease (6%). The median numbers of CD3+ TILs, CD4+ TILs, and CD8+ TILs in the preirradiation tumor tissue were 49 (interquartile range [IQR], 36-80), 45 (IQR, 28-57), and 19 (IQR, 8-35), respectively. The number of preirradiation TILs did not differ significantly between responders and nonresponders. The median numbers of CD3+ TILs, CD4+ TILs, and CD8+ TILs in postirradiation tumor tissue were 17 (IQR, 13-31), 26 (IQR, 16-35), and 7 (IQR, 5-11), respectively. CONCLUSIONS: After preoperative PBI in this limited cohort, the number of TILs in tumor tissue decreased. No differences in numbers of preirradiation TILs between responders and nonresponders were observed.

Tumor Response After Neoadjuvant Magnetic Resonance Guided Single Ablative Dose Partial Breast Irradiation.

PURPOSE: 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). METHODS AND MATERIALS: 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). RESULTS: 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. CONCLUSIONS: 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.

Treatment constraints for single dose external beam preoperative partial breast irradiation in early-stage breast cancer.

BACKGROUND: Following breast-conserving surgery and post-operative 3D-conformal accelerated partial breast irradiation (APBI), suboptimal cosmetic results have been reported. Preoperative radiation delivery to the intact tumor enables better target visualization and treatment volume reduction. Single dose preoperative APBI has the potential to improve toxicity profiles, reduce treatment burden and enable in vivo exploration of breast cancer radiogenomics. PURPOSE: Develop practical guidelines for single dose external beam preoperative APBI. METHODS: Recommended dose constraints were derived from pooled dosimetry estimates from 2 clinical trials. In an American dose escalation trial, a uniform 15, 18 or 21 Gy dose has previously been evaluated for non-lobular cT1N0 or low/intermediate grade DCIS <2 cm in prone position (n = 32). In the Netherlands, the feasibility of ablative APBI (20 Gy to GTV, 15 Gy to CTV) to non-lobular cT1N0 in supine position, is currently being explored (n = 15). The dosimetric adherence to the developed constraints was evaluated in new APBI plans with a 21 Gy uniform dose but an extended CTV margin (n = 32). RESULTS: Dosimetric data pooling enabled the development of practical guidelines for single dose preoperative APBI. CONCLUSION: The developed guidelines will allow further explorations in the promising field of single dose preoperative external beam APBI for breast cancer treatment.

Quantification of intra-fraction motion in breast radiotherapy using supine magnetic resonance imaging.

In early-stage breast-cancer patients, accelerated partial-breast irradiation techniques (APBI) and hypofractionation are increasingly implemented after breast-conserving surgery (BCS). For a safe and effective radiation therapy (RT), the influence of intra-fraction motion during dose delivery becomes more important as associated fraction durations increase and targets become smaller. Current image-guidance techniques are insufficient to characterize local target movement in high temporal and spatial resolution for extended durations. Magnetic resonance imaging (MRI) can provide high soft-tissue contrast, allow fast imaging, and acquire images during longer periods. The goal of this study was to quantify intra-fraction motion using MRI scans from 21 breast-cancer patients, before and after BCS, in supine RT position, on two time scales. High-temporal 2-dimensional (2D) MRI scans (cine-MRI), acquired every 0.3 s during 2 min, and three 3D MRI scans, acquired over 20 min, were performed. The tumor (bed) and whole breast were delineated on 3D scans and delineations were transferred to the cine-MRI series. Consecutive scans were rigidly registered and delineations were transformed accordingly. Motion in sub-second time-scale (derived from cine-MRI) was generally regular and limited to a median of 2 mm. Infrequently, large deviations were observed, induced by deep inspiration, but these were temporary. Movement on multi-minute scale (derived from 3D MRI) varied more, although medians were restricted to 2.2 mm or lower. Large whole-body displacements (up to 14 mm over 19 min) were sparsely observed. The impact of motion on standard RT techniques is likely small. However, in novel hypofractionated APBI techniques, whole-body shifts may affect adequate RT delivery, given the increasing fraction durations and smaller targets. Motion management may thus be required. For this, on-line MRI guidance could be provided by a hybrid MRI/RT modality, such as the University Medical Center Utrecht MRI linear accelerator.

MRI-guided single fraction ablative radiotherapy for early-stage breast cancer: a brachytherapy versus volumetric modulated arc therapy dosimetry study.

BACKGROUND AND PURPOSE: A radiosurgical treatment approach for early-stage breast cancer has the potential to minimize the patient's treatment burden. The dosimetric feasibility for single fraction ablative radiotherapy was evaluated by comparing volumetric modulated arc therapy (VMAT) with an interstitial multicatheter brachytherapy (IMB) approach. METHODS AND MATERIALS: The tumors of 20 patients with early-stage breast cancer were delineated on a preoperative contrast-enhanced planning CT-scan, co-registered with a contrast-enhanced magnetic resonance imaging (MRI), both in radiotherapy supine position. A dose of 15 Gy was prescribed to the planned target volume of the clinical target volume (PTVCTV), and 20 Gy integrated boost to the PTV of the gross tumor volume (PTVGTV). Treatment plans for IMB and VMAT were optimized for adequate target volume coverage and minimal organs at risk (OAR) dose. RESULTS: The median PTVGTV/CTV receiving at least 95% of the prescribed dose was ⩾99% with both techniques. The median PTVCTV unintentionally receiving 95% of the prescribed PTVGTV dose was 65.4% and 4.3% with IMB and VMAT, respectively. OAR doses were comparable with both techniques. CONCLUSION: MRI-guided single fraction radiotherapy with an integrated ablative boost to the GTV is dosimetrically feasible with both techniques. We perceive IMB less suitable for clinical implementation due to PTVCTV overdosage. Future studies have to confirm the clinical feasibility of the single fraction ablative approach.