Preoperative Partial Breast Irradiation Research Articles

A narrative review for radiation oncologists to implement preoperative partial breast irradiation.

The strategy to anticipate radiotherapy (RT) before surgery, for breast cancer (BC) treatment, has recently generated a renewed interest. Historically, preoperative RT has remained confined either to highly selected patients, in the context of personalized therapy, or to clinical research protocols. Nevertheless, in the recent years, thanks to technological advances and increased tumor biology understanding, RT has undergone great changes that have also impacted the preoperative settings, embracing the modern approach to breast cancer. In particular, the reappraisal of preoperative RT can be viewed within the broader view of personalized and tailored medicine. In fact, preoperative accelerated partial breast irradiation (APBI) allows a more precise target delineation, with less variability in contouring among radiation oncologists, and a smaller treatment volume, possibly leading to lower toxicity and to dose escalation programs. The aim of the present review, which represents a benchmark study for the AIRC IG-23118, is to report available data on different technical aspects of preoperative RT including dosimetric studies, patient's selection and set-up, constraints, target delineation and clinical results. These data, along with the ones that will become available from ongoing studies, may inform the design of the future trials and representing a step toward a tailored APBI approach with the potential to challenge the current treatment paradigm in early-stage BC.Trial registration: The study is registered at clinicaltrials.gov (NCT04679454).

Abstract PD3-03: Preoperative robotic radiosurgery for early breast cancer: results of the phase II ROCK trial (NCT03520894)

Abstract Introduction. Breast-conserving surgery (BCS) followed by postoperative radiotherapy (RT) still represents the standard of care for early breast cancer (BC) patients. Hypofractionated schedules in maximum 15 fractions are currently accepted as the gold standard for external beam whole and partial breast irradiation (PBI). PBI for selected early BC patients allowed a shorter overall treatment duration and an improved patient compliance as compared to old-fashioned RT schedules. Preoperative PBI, due to the advantage of treating a well-defined volume, has been gaining attention in this multidisciplinary scenario. It avoids local treatment delay and might allow tumour downstaging with increased rates of BCS and improved cosmetic outcomes. Since local recurrence might be driven by biological mechanisms of radioresistance rather than geographical miss, higher dose per fraction may overcome repair mechanisms allowing tumoral cells to escape from conventional RT damage. We report the results of the phase II ROCK trial (NCT03520894), enrolling early BC patients treated with preoperative robotic radiosurgery (prRS), in terms of acute and early late toxicity, disease control, and cosmesis. Material and methods. The study recruited between August 2018 and September 2021 at the Radiation Oncology Unit of the University of Florence (Florence, Italy). Eligible patients were women aged 50+ years, with histologically proven invasive early BC, HR+/HER2- disease, without lymph vascular invasion, tumour size up to 25 mm suitable for BCS. Exclusion criteria were clinical node positive disease, multiple foci tumours, and patients with breast lesion limiting within 5 mm from the skin surface. The study aimed to prospectively assess the safety and feasibility of a single Cyberknife® (Accuray Incorporated, Sunnyvale, CA, USA) 21Gy-fraction prRS in preoperative setting, and to identify predictive factors for outcomes based on biologic and clinical features. The primary endpoint was the acute skin toxicity (from the end of prRS to surgery) according to the RTOG and the EORTC scales. Secondary endpoints were the rate of early late skin and non-skin toxicity as measured 90 days from the end of prRS, the rate of pathological complete response (pCR) according to Chevalier score. Cosmetic outcomes were prospectively scored every 6-month using the BCCT.core software. Results. From August 2018 to September 2021, a total of 70 patients were recruited and enrolled. Of those, 41 were excluded due to tumour biology exclusion criteria and 7 due to multiple foci breast disease evidenced at basal MRI. Therefore, 22 patients were successfully treated with pRS. Median age at diagnosis was 68 years (range 50-86), median tumour size was 14 mm (range 7.5-25). Required target dosimetric parameters were met in all patients, as well as normal tissue constraints. Patients received surgery after a median time of 29 days from biopsy, without any delay or postoperative complication. Overall, three G1 adverse events (13.6%) were recorded within 7 days from prRS (1 erythema, 2 breast pain). Three events (13.6%) were recorded between 7 and 30 days from prRS, one G2 breast oedema and two G1 breast pain. No acute toxicity greater than G2 was recorded. Five patients experienced early late G1 toxicity (1 breast pain, 4 breast induration). One patient reported G2 breast induration. No early late toxicity greater than G2 was observed. At a median follow up of 18 months (range 6-29.8), cosmetic results were scored excellent/good and fair in 14 and 5 patients, respectively, while 3 patients experienced a poor cosmetic outcome. Overall, pCR after surgery was reported in 2 patients (9%). Two patients received postoperative whole breast irradiation, according to histopathological results. Conclusions. ROCK trial showed that a single 21 Gy dose prRS represents a feasible technique for selected patients affected by early BC, showing a good safety profile and a promising effectiveness. Citation Format: Icro Meattini, Giulio Francolini, Vanessa Di Cataldo, Luca Visani, Carlotta Becherini, Erika Scoccimarro, Monica Mangoni, Viola Salvestrini, Laura Masi, Chiara Bellini, Raffaela Doro, Federica Di Naro, Marco Bernini, Jacopo Nori, Lorenzo Orzalesi, Simonetta Bianchi, Lorenzo Livi. Preoperative robotic radiosurgery for early breast cancer: results of the phase II ROCK trial (NCT03520894) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD3-03.

Pre-operative partial breast irradiation: revolutionizing radiation treatment for women with early stage breast cancer.

Partial breast irradiation (PBI) has been increasingly accepted as a suitable component of breast conservation in the management of patients with early stage breast cancer, however the majority of existing studies have focused on the use of adjuvant or intra-operative techniques. Several early stage studies have more recently shown that PBI can be safely used in the pre-operative setting. Early data show similar local control without evidence of increased toxicity or worsening cosmesis, as compared to postoperative PBI or standard whole breast irradiation. While long term data are still maturing, pre-operative accelerated PBI (PAPBI) offers a number of possible clinical advantages including reducing the treatment field and increasing the number of patients eligible for PBI, identifying biomarkers of response to radiation, and improving the rates of breast conservation and treatment compliance. This review discusses key concepts and controversies surrounding PBI as it has increasingly been adopted in the US, Canada, and Europe, and introduces the concepts and early studies of PAPBI. In addition, we summarize ongoing clinical trials investigating PAPBI, review clinical benefits and challenges associated with PAPBI versus postoperative PBI, and discuss ongoing limitations as well as next generation technologies important to the implementation of PAPBI in the management of patients with early-stage localized breast cancer.

145 (PB-058) Poster - Preoperative partial breast irradiation in low-risk breast cancer patients: a systematic review of literature

Background: Since 2017, partial breast irradiation (PBI) is considered standard treatment after breast conserving surgery (BCS) in breast cancer patients with a low risk on recurrence. In order to reduce the irradiated breast tissue volume, toxicity, and the number of radiotherapy sessions, PBI can be performed preoperatively. In this study, we assessed the clinical and oncological outcomes of preoperative PBI.

Partial breast irradiation: An updated consensus statement from the American brachytherapy society

PurposeIn recent years, results with mature follow-up have been reported for several Phase III trials randomizing women to receive whole breast irradiation (WBI) versus varying modalities of partial breast irradiation (PBI). It is important to recognize that these methods vary in terms of volume of breast tissue treated, dose per fraction, and duration of therapy. As such, clinical and technical guidelines may vary among the various PBI techniques. MethodsMembers of the American Brachytherapy Society with expertise in PBI performed an extensive literature review focusing on the highest quality data available for the numerous PBI options offered in the modern era. Data were evaluated for strength of evidence and published outcomes were assessed. ResultsThe majority of women enrolled on randomized trials of WBI versus PBI have been age >45 years with tumor size <3 cm, negative margins, and negative lymph nodes. The panel also concluded that PBI can be offered to selected women with estrogen receptor negative and/or Her2 amplified breast cancer, as well as ductal carcinoma in situ, and should generally be avoided in women with extensive lymphovascular space invasion. ConclusionsThis updated guideline summarizes published clinical trials of PBI methods. The panel also highlights the role of PBI for women facing special circumstances, such as history of cosmetic breast augmentation or prior breast irradiation, and discusses promising novel modalities that are currently under study, such as ultrashort and preoperative PBI. Updated consensus guidelines are also provided to inform patient selection for PBI and to characterize the strength of evidence to support varying PBI modalities.

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

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. 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. 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. 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.

Altered fractionation in radiation therapy for breast cancer in the elderly: are we moving forward?

Radiotherapy is a pivotal treatment for treating breast cancer. However, its role in the management of elderly patients is still under debate. Some authors suggest be avoided after surgery for early stage, some others advocate its adoption. For breast cancer treatment different schedules are used both for whole and partial breast irradiation, in adjuvant as well as definitive setting. Which one is better for elderly patients is a controversial topic. Numerous studies focused on both moderate or extreme hypofractionated irradiation have been published. However, only few addressed the topic on elderly patient population. The data on hypofractionated radiotherapy showed that for whole breast, locoregional and post-mastectomy treatment, this approach is a valid option reporting similar efficacy and toxicity to the standard fractionation. Also accelerated partial breast irradiation for patients with favourable early stage disease represents a viable option allowing for de-escalation by targeting radiation dose to the part of breast tissue at highest recurrence risk. Undoubtedly, for frail and elderly patients a short course of radiotherapy could increase their adherence and the quality of life. In the same manner, the preoperative approach has been applied for both whole and partial breast irradiation, allowing for more precise target delineation compared to the post-surgical one, eventually leading to a smaller treatment volume, to less geographical missing and possibly to a lower radiation-induced toxicity. Some more long-term results could make us more confident in prescribing adjuvant or preoperative partial breast irradiation. These approaches could be the most appropriate treatment for elderly patients, potentially preserving quality of life and increasing the tolerability to the irradiation.

EP-1312 Evaluation of MRI-based guidelines for contouring tumors for preoperative partial breast irradiation

EP-1312 Evaluation of MRI-based guidelines for contouring tumors for preoperative partial breast irradiation

OC-0591 Response after MR-guided single dose ablative preoperative partial breast irradiation

OC-0591 Response after MR-guided single dose ablative preoperative partial breast irradiation

Findings on Surveillance Imaging After Preoperative Partial Breast Irradiation for Early Stage Breast Cancer

To evaluate the mammographic sequelae of preoperative accelerated partial breast irradiation (APBI) delivered via either stereotactic radiosurgery or a conventionally fractionated regimen. This multicenter, retrospective study evaluated surveillance mammograms from patients enrolled in 2 prospective, preoperative APBI clinical trials. At 1 site, 31 patients with cT1N0 invasive carcinomas or low- or intermediate-grade ductal carcinoma in situ (<2cm) received preoperative stereotactic radiosurgery and had a total of 186 mammograms available for review. At the second site, 180 mammograms from 25 patients with cT1-2 (<3cm) unifocal invasive carcinomas treated with conventionally fractionated, preoperative APBI were reviewed. Findings were compared with those of 26 early stage breast cancers treated with conventional postoperative whole breast radiation therapy. At a median follow-up of 61months, 17 patients (55%) treated with single-dose APBI exhibited exuberant fat necrosis at the lumpectomy site. Fat necrosis was believed to be clinically palpable in 5 (16%) of these patients within the first 3years of follow-up. Exuberant fat necrosis developed in 5 patients (20%) treated with fractionated APBI over a median 68-month follow-up period but only 2 of those patients (8%) who underwent conventional whole breast radiation therapy. In situ tumor targeting in the preoperative setting allows relative sparing of normal tissue but results in a larger and more vigorous area of change on surveillance imaging, potentially reflecting the interaction of surgical resection with an irradiated tissue bed. High-dose stereotactic radiosurgery in particular increases the risk of developing a uniquely robust and well-demarcated pattern of fat necrosis onmammogram that may also present clinically. With many ongoing studies evaluating the preoperative treatment approach, defining the landscape of expected imaging sequelae will provide useful anticipatory guidance for clinicians and patients.

Pathologic Response and Acute Toxicity: Planned Interim Analysis of the Phase 2 NeoRT Trial Evaluating Preoperative Single Fraction Partial Breast Radiation Therapy in Early Stage Breast Cancer

Pre-operative partial breast irradiation (PBI) has been explored as an alternative to adjuvant breast radiotherapy. Practically, this approach has the potential to limit treatment volumes while simultaneously providing an avenue to study breast cancer radiation response. In this Phase II study, we hypothesized that 20% of patients would have a complete pathologic response at surgical resection six weeks after preoperative radiation. Histologically confirmed breast cancer patients with ER(+) or PR(+), Her2(-) T1N0 invasive breast cancer or Tis <2cm were enrolled in this single institution, IRB approved, Phase II study delivering 21Gy preoperatively to the intact tumor. Toxicity was scored using CTCAE version 4.0. Any toxicity possibly, probably or definitely related to radiotherapy is reported. Interim analysis was planned to assess complete pathologic response rates, defined as no residual invasive or in-situ tumor. Residual cancer burden (RCB) was also calculated. 20 of 40 planned patients have been enrolled. Three patients were subsequently ineligible on MRI but fifteen have proceeded to surgical resection. Two patients have received radiation but not surgery at the time of this analysis. The median age was 61 (range 58-77), 87% of patients were white and 87% had invasive ductal carcinoma. One patient had a post-operative wound infection and grade 3 seroma requiring drain placement. A second patient had a small area of wound dehiscence with seroma leakage. Remaining toxicities were grade 1-2 and consisted primarily of discomfort, seroma, fatigue and skin change. Pathologic complete response was noted in 1 patient (7%). Another had a pCR by RCB assessment, both with DCIS on pre-treatment biopsy. 5 patients (33%) had an RCB of I, and 8 patients (53%) an RCB of II. Fifteen women with early stage breast cancer have completed a single preoperative fraction of 21Gy followed by surgical resection at six weeks. Two (13%) grade 3 post-operative toxicities and one (7%) pathologic complete response were noted. This interim analysis suggests an increase in post-operative complications relative to our Phase I experience and a low rate of complete pathologic response in invasive disease. We plan to increase accrual in order to better define the optimal timing of surgical excision relative to operative complications and tumor response.

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

BackgroundFollowing 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. PurposeDevelop practical guidelines for single dose external beam preoperative APBI. MethodsRecommended dose constraints were derived from pooled dosimetry estimates from 2 clinical trials. In an American dose escalation trial, a uniform 15, 18 or 21Gy dose has previously been evaluated for non-lobular cT1N0 or low/intermediate grade DCIS <2cm in prone position (n=32). In the Netherlands, the feasibility of ablative APBI (20Gy to GTV, 15Gy 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 21Gy uniform dose but an extended CTV margin (n=32). ResultsDosimetric data pooling enabled the development of practical guidelines for single dose preoperative APBI. ConclusionThe developed guidelines will allow further explorations in the promising field of single dose preoperative external beam APBI for breast cancer treatment.

Dosimetric Feasibility of Preoperative Partial Breast Irradiation in Prone Position Using a Magnetic Resonance Linear Accelerator

Dosimetric Feasibility of Preoperative Partial Breast Irradiation in Prone Position Using a Magnetic Resonance Linear Accelerator

E01. Striving for the optimum

The treatment of early breast cancer has changed drastically, from avoidance of mastectomy to preoperative partial breast irradiation, and to an individualized approach for adjuvant treatment. These changes became possible as a result of the inclusion of modern imaging before and during surgery and radiotherapy, and by selecting adjuvant treatment on prognostic and (soon) predictive molecular biological assays. All this has led to a major improvement in treatment outcomes, as shown by the results from several trials performed over recent decades. These trials have led us to ask new questions: in particular, how will molecular biology guide the treatment of early breast cancer towards precision medicine? An intriguing issue is the age effect in breast cancer patients. Although long-term follow-up has revealed that mastectomy results in survival equal to that of breastconserving therapy (BCT) [1], the boost versus no boost trial showed a dramatic age effect in young patients in that they had many more local recurrences than older patients [2] (Fig. 1). This trial aimed at reducing the required radiation dose for BCT, weighing the side effects (i.e. fibrosis) against improved tumor control. Fortunately it was shown that younger patients benefited from a higher radiation in the European Organisation for Research and Treatment of Cancer (EORTC) boost versus no boost trial, while in older patients a lower radiation dose was sufficient [3] (Fig. 2).

Has partial breast irradiation by IORT or brachytherapy been prematurely introduced into the clinic?

In contrast to most new oncology treatments, wide clinical introduction of partial breast irradiation (PBI) is not based on level A trial evidence. Despite promising phase I/II data, new reports based upon large cohorts of patients mention more recurrences and/or complications from PBI compared with whole breast irradiation (WBI), necessitating more careful selection of patients for PBI while awaiting long term results of major clinical trials. In an attempt to improve this we give preoperative PBI within a prospective trial.

P2-08-04: Computer-Derived Breast MRI Features Have Complementary Value for Preoperative Selection of Systemic Drug Therapy in Node-Negative Stage-I/II Breast Cancer Patients.

Abstract Background: Typical guidelines for adjuvant systemic drug therapy require assessment of lymph node status, tumor extent and grade. Increasing interest exists, however, for preoperative therapy (neoadjuvant drug therapy and preoperative partial breast irradiation). Here, representative excision specimens are not available to assess eligibility for systemic therapy. Moreover, tumor grade may be difficult to assess in core biopsies resulting in underestimation rates up to 40%. Contrast-enhanced MRI has been shown to correlate with underlying tumor biology, but it is unknown whether it can complement eligibility criteria for systemic drug therapy. Purpose: To assess the complementary value of MRI to determine eligibility for systemic drug therapy prior to breast-conserving surgery in node-negative stage-I/II breast cancer patients. Materials and methods: Patients with preoperative node-negative invasive breast cancer ≥1.0 cm and eligible for breast-conserving therapy after conventional breast imaging and MRI were consecutively included between February 2000 and March 2007. Informed consent was obtained from all patients. Eligibility to systemic therapy was determined on the basis of national guidelines using age, size, tumor grade, as well as axillary lymph node status at final pathology. Twenty temporal and morphological features of contrast uptake at MRI were automatically analyzed by a previously build CAD workstation1,2. Preoperative lymph node status was derived from ultrasound-guided fine-needle aspiration. Multivariate logistic regression and receiver-operating characteristics (ROC) analysis was used to assess associations between preoperative features (age, ER status, computer-extracted MRI features) and eligibility to systemic therapy based on post-operative features (tumor size, grade, lymph node status). Results: Three-hundred-and-eighty-six patients were included. The mean patient age was 58 years. The mean tumor size at pathology was 1.6 cm. Tumor grade was I, II and III in 128 (33%), 163 (42%), and 94 (24%) of tumors, respectively. Post-operative lymph node status was positive in 115/386 (30%) patients. In total, 262/386 (68%) patients were eligible for systemic drug therapy based on post-operative pathology. Multivariate analysis of preoperatively available features yielded ER status, and principle components 1, 6, 8 and 15 of the computer-extracted features. These components describe tumor volume and shape, heterogeneity of contrast uptake, late-enhancement kinetics, and probability of malignancy. The resulting model correlated with the Adjuvant! program (R=0.55, p&amp;lt;0.0001). The area under the ROC curve was 0.82 (p&amp;lt;0.0001). Without the model, agreement between preoperative and postoperative assessment of eligibility to drug therapy was 232/386 (60%) at 15/124 (12%) overestimation rate. With the MRI model, it increased to 258/386 (67%) (p=0.004) without increasing overestimation rate. Conclusion: Computer-analysis of contrast-enhanced MRI has potential to complement preoperative selection of stage I/II node-negative breast-cancer patients for systemic drug therapy. Ref: 1. Gilhuijs et al., Radiology 2002; 225: 907–916 2. Deurloo et al., Radiology 2005; 234: 693–701 Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-08-04.

Preoperative Single Fraction Partial Breast Radiotherapy for Early-Stage Breast Cancer

Several recent series evaluating external beam accelerated partial breast irradiation (PBI) have reported adverse cosmetic outcomes, possibly related to large volumes of normal tissue receiving near-prescription doses. We hypothesized that delivery of external beam PBI in a single fraction to the preoperative tumor volume would be feasible and result in a decreased dose to the uninvolved breast compared with institutional postoperative PBI historical controls. A total of 17 patients with unifocal Stage T1 breast cancer were identified. Contrast-enhanced subtraction magnetic resonance images were loaded into an Eclipse treatment planning system and used to define the target volumes. A "virtual plan" was created using four photon beams in a noncoplanar beam arrangement and optimized to deliver 15 Gy to the planning target volume. The median breast volume was 1,713 cm(3) (range: 1,014-2,140), and the median clinical target volume was 44 cm(3) (range: 26-73). In all cases, 100% of the prescription dose covered 95% of the clinical target volume. The median conformity index was 0.86 (range: 0.70-1.12). The median percentage of the ipsilateral breast volume receiving 100% and 50% of the prescribed dose was 3.8% (range: 2.2-6.9) and 13.3% (range: 7.5-20.8) compared with 18% (range: 3-42) and 53% (range: 24-65) in the institutional historical controls treated with postoperative external beam PBI (p = .002). The median maximum skin dose was 9 Gy. The median dose to 1 and 10 cm(3) of skin was 6.7 and 4.9 Gy. The doses to the heart and ipsilateral lung were negligible. Preoperative PBI resulted in a substantial reduction in ipsilateral breast tissue dose compared with postoperative PBI. The skin dose appeared reasonable, given the small volumes. A prospective Phase I trial evaluating this technique is ongoing.