Stereotactic image-guided neoadjuvant ablative single-dose radiation, then lumpectomy, for early breast cancer: the SIGNAL prospective single-arm trial of single-dose radiation therapy

Original Article

Stereotactic image-guided neoadjuvant ablative single-dose radiation, then lumpectomy, for early breast cancer: the SIGNAL prospective single-arm trial of single-dose radiation therapy

K. Guidolin, MD*, B. Yaremko, MSc MD, K. Lynn, BSc (Hons)§, S. Gaede, PhD||, A. Kornecki, MD#, G. Muscedere, MD#, I. BenNachum, MD#, O. Shmuilovich, MD#, M. Mouawad, MSc, E. Yu, MD PhD*, T. Sexton, MD PhD*,, N. Gelman, PhD#, V. Moiseenko, PhD**, M. Brackstone, MD PhD††, M. Lock, MD*



Background and Purpose

Adjuvant whole-breast irradiation after breast-conserving surgery, typically delivered over several weeks, is the traditional standard of care for low-risk breast cancer. More recently, hypofractionated, partial-breast irradiation has increasingly become established. Neoadjuvant single-fraction radiotherapy (rt) is an uncommon approach wherein the unresected lesion is irradiated preoperatively in a single fraction. We developed the signal (Stereotactic Image-Guided Neoadjuvant Ablative Radiation Then Lumpectomy) trial, a prospective single-arm trial to test our hypothesis that, for low-risk carcinoma of the breast, the preoperative single-fraction approach would be feasible and safe.


Patients presenting with early-stage (T < 3 cm), estrogen-positive, clinically node-negative invasive carcinoma of the breast with tumours at least 2 cm away from skin and chest wall were enrolled. All patients received prone breast magnetic resonance imaging (mri) and prone computed tomography simulation. Treatable patients received a single 21 Gy fraction of external-beam rt (as volumetric-modulated arc therapy) to the primary lesion in the breast, followed by definitive surgery 1 week later. The primary endpoints at 3 weeks, 6 months, and 1 year were toxicity and cosmesis (that is, safety) and feasibility (defined as the proportion of mri-appropriate patients receiving rt).


Of 52 patients accrued, 27 were successfully treated. The initial dosimetric constraints resulted in a feasibility failure, because only 57% of eligible patients were successfully treated. Revised dosimetric constraints were developed, after which 100% of patients meeting mri criteria were treated according to protocol. At 3 weeks, 6 months, and 1 year after the operation, toxicity, patient- and physician-rated cosmesis, and quality of life were not significantly different from baseline.


The signal trial presents a feasible method of implementing single-dose preoperative rt in early-stage breast cancer. This pilot study did not identify any significant toxicity and demonstrated excellent cosmetic and quality-of-life outcomes. Future randomized multi-arm studies are required to corroborate these findings.

KEYWORDS: Radiation oncology, stereotactic body radiotherapy, sbrt


The modern management of low-risk breast cancer involves the use of breast-conserving surgery plus radiotherapy (rt), which can be hypofractionated without sacrificing efficacy or safety compared with standard rt (that is, 50 Gy in 25 fractions)17. Recently, accelerated partial-breast irradiation was postulated to be a viable treatment option for low-risk disease, given that most local recurrences are located in the lumpectomy cavity8,9.

The most accelerated example of accelerated partial-breast irradiation is single-fraction radiation therapy (sfrt), which is well established in the literature and has been used to treat large cohorts of women with low-risk breast cancer, with acceptable clinical outcomes10,11. The technique is more convenient and might reduce health care costs by freeing space on radiation treatment units. Furthermore, sfrt might entice more women to undergo standard-of-care treatment (that is, breast-conserving surgery with rt), because the primary reasons for underuse of adjuvant rt after breast-conserving surgery are the time, travel, and effort required12,13. Despite such benefits, the risk of treatment-related toxicity is increased for sfrt compared with standard techniques, and the treatment planning and delivery platforms historically required for sfrt have not been widely available, which limit use of the technique in North America14. In Canada, intraoperative rt is cost-prohibitive because of the expense of disposable components, and it is currently used in very few centres. With the movement toward hypofractionation in the radiotherapeutic management of low-risk carcinoma of the breast in general, a discussion of how best to implement and to incorporate sfrt into routine clinical practice is very timely.

We therefore developed signal (Stereotactic Image-Guided Neoadjuvant Ablative Radiation Then Lumpectomy), a single-arm, single-institution clinical trial in which a cohort of women with early-stage low-risk carcinoma of the breast would be treated with neoadjuvant rt delivered 1 week before lumpectomy15. Based on a dose-escalation trial and another single-arm trial, and radiobiologic calculations described previously1517, we selected 21 Gy in 1 fraction, delivered prone, by external-beam volumetric modulated arc therapy, with dosimetry planning based on computed tomography (ct) simulation images co-registered with magnetic resonance imaging (mri) images. Our objectives were to evaluate the feasibility and safety of this approach in a pilot design as a guide for future randomized controlled studies. Our hypothesis was that, for selected patients with low-risk breast carcinoma, neoadjuvant partial-breast hypofractionated stereotactic body rt (sbrt) would be technically feasible, with acceptable toxicity and cosmesis. Here, we report the toxicity and cosmesis outcomes observed in a cohort of patients treated using that regimen.


The signal protocol was previously published, and Figure 1 shows the study schema15. Two primary endpoints were considered in signal: radiation toxicity and feasibility. Radiation toxicity was defined as grade 2 or greater toxicity (such as fibrosis), measured using the Common Terminology Criteria for Adverse Events18. Feasibility was defined as the ability to deliver treatment in accordance with the study-defined dosimetry constraints in 90% or more of the patients. Secondary endpoints were cosmesis (scored by the patient and the radiation oncologist or surgeon using the Modified Harvard–Harris Cosmetic Scale19) and quality of life (qol) measured using the Functional Assessment of Cancer Therapy–Breast tool20. Postoperative complications were also collected, analyzed, and reported. Approval for signal was given by Western University’s Health Sciences Research Ethics Board (no. 105643), and the trial was registered with (NCT02212860).



FIGURE 1 Study schema showing the entire course of the experimental protocol undergone by the patients. QOL = quality of life; MR = magnetic resonance; CT = computed tomography; RT = radiotherapy.

All postmenopausal women presenting for surgical consultation between 2014 and 2016 with a new diagnosis of early-stage (<3 cm in size, node-negative), estrogen receptor–positive, unifocal breast cancer were approached for participation. If initial ultrasonography suggested sufficient distance (that is, ≥2 cm) both between the lesion and the skin and between the lesion and chest wall, patients were enrolled.

Once enrolled, patients underwent ultrasound-guided insertion of a surgical clip as a fiducial marker. They were then immobilized on a prone breast board and were imaged by contrast-enhanced prone breast mri. If mri confirmed unifocal disease less than 3 cm that was sufficiently distant from the skin and the chest wall, patients proceeded to radiation treatment planning. All patients reaching planning were again positioned and immobilized on a prone breast board for ct simulation. Using rigid body registration, the prone breast mri was fused onto the prone ct simulation images. The gross tumour volume (gtv) was defined as the primary breast lesion seen on mri. The clinical target volume was defined as the gtv plus a 5 mm margin. The planning target volume (ptv) was defined as the clinical target volume plus a 5 mm margin. Radiation treatment plans were devised to deliver a prescription dose of 21 Gy to the ptv in a single fraction.

With the patient in prone position, 21 Gy was delivered by sbrt, using cone-beam ct imaging to confirm patient positioning and the accuracy of delivery by using the surgical clip to localize the tumour. Real-time image acquisition monitored patient positioning and allowed the beam to be disabled if the patient moved significantly. Relevant as-treated dosimetric constraints were based on a thorough review of the relevant published literature, published sbrt-based clinical trials, and general radiobiologic principles (Table I). After induction rt, radiolocalizing 125I seeds were placed adjacent to the surgical clip to facilitate localization and guided excision. All patients underwent breast-conserving surgery and sentinel lymph node biopsy (where clinically indicated), ideally within 1 week of rt. Older patients could opt out of sentinel lymph node biopsy in accordance with clinical guidelines. Toxicity, cosmesis (patient- and physician-assessed), and qol measures were collected at baseline and at 3 weeks, 6 months, and 1 year postoperatively. Toxicity was reported as the number of patients who experienced any grade 2 or greater toxicity at each time point, with comparison to baseline by the Fisher exact test. To allow for comparisons to other publications using the Modified Harvard–Harris Cosmetic Scale in breast irradiation trials, the cosmesis score (excellent, good, fair, poor) was collapsed into the proportion of patients or physicians rating the cosmesis as excellent or good or as fair or poor. The proportion of patients or physicians reporting a good or excellent cosmetic score at each time point was compared with baseline using the Fisher exact test. The qol total score at each time point was compared with baseline using the Student t-test.

TABLE I Normal tissue dosimetric limits,a original and revised



Between February 2014 and September 2016, 53 patients were approached for participation, and 52 patients were initially enrolled (Figure 2). Of those 52 patients, 13 were excluded at the time of mri (2 were upstaged by mri, 5 did not fit in the mri bore or were unable to remain still, and 6 did not meet the study criteria because of proximity of the tumour to skin or chest wall as measured on mri). Of the remaining 39 patients who met the criteria for breast mri and who went on to radiation treatment planning, the study-specified dosimetric constraints could not be met in 12 (in every case, either the chest wall or the skin constraint, or both, could not be met). Those patients were taken off the study protocol and instead went on to surgery and standard whole-breast adjuvant rt.



FIGURE 2 Patient flow diagram. MR = magnetic resonance; CT = computed tomography; RT = radiotherapy.

The remaining patients fell into one of two distinct cohorts depending on when they were treated (Figure 2). The first of those cohorts consisted of the first 36 patients approached (the “initial cohort”). Of those 36 patients, 8 were excluded at the time of mri (2 were upstaged by mri, 2 did not fit in the mri bore, and 4 did not meet the study criteria because of proximity of the tumour to skin or chest wall). The study-defined dosimetric constraints could not be met in 12 of the remaining 28 patients (the same 12 already mentioned).

Therefore, in the initial cohort, only 16 of 28 patients meeting the study criteria by breast mri went on to receive the study-defined treatment, representing a cohort-specific success rate of 57%. That result was deemed a failure of the approach, triggering an interim review as required by the protocol. During the interim review, we concluded that our dosimetric constraints were too restrictive, especially with respect to dose to skin. We similarly concluded that our original definition of skin (external contour less 5 mm) was too restrictive and more conservative than had been used in similar published clinical trials of sfrt21. Revised dosimetric constraints were therefore developed (Table I) and implemented to treat the next 16 patients who were accrued (the “revised cohort”). Of those 16 patients, 5 were excluded at the time of mri (3 did not fit in the mri bore; 2 did not meet the criteria for proximity of the tumour to skin or chest wall). Of the remaining 11 patients, all went on to receive the study-defined treatment, representing a cohort-specific success rate of 100%. The actual mean dose delivered in both patient cohorts was similar whether the cohort underwent treatment at the initial dosimetric constraints or at the revised constraints (Table II).

TABLE II As-treated target dosimetry doses, averaged over the study cohorts


All treated patients underwent local excision of the primary tumour to negative margins within 7 days of radiation, without any delay or complication. No patients showed signs of erythema at the time of surgery, none described any pain, and every patient expressed pleasure with the entire process. No surgery was made more complicated as a result of the preoperative radiation, and in fact the tissues appeared healthy and normal. No postoperative complications were encountered. No patients required in situ drains, and none had prolonged seroma, wound dehiscence, skin necrosis, or infection in the postoperative period.

Table III presents patient demographics and tumour details. Toxicity, cosmesis (patient- and physician-assessed), and qol measures (all assessed at baseline and at 3 weeks, 6 months, and 1 year postoperatively) are presented in Table IV. No patients experienced toxicity of grade 2 or higher at baseline or at 3 weeks or 1 year postoperatively, and 1 of 27 evaluable patients had a grade 2 delayed wound infection at the 6-month postoperative visit, which was not significantly different from baseline (p = 1.0). Physician-rated cosmesis (Harvard–Harris score) was slightly worse than baseline (100% judged good or excellent) at 3 weeks (93% judged good or excellent, p = 0.16), 6 months (96% judged good or excellent, p = 0.29), and 1 year (92% judged good or excellent, p = 0.13) postoperatively, but none of the differences were statistically significant. Physician-rated cosmetic outcomes for the patients was judged 96% good or excellent at baseline and 93% at 3 weeks (p = 0.60), 92% at 6 months (p = 0.53), and 96% at 1 year (p = 0.98) post-operatively. Again, none of those changes were statistically significant. Compared with baseline, qol was significantly improved at 3 weeks (p = 0.01) and at 1 year postoperatively (p = 0.001) and was elevated, although not significantly so, at 6 months postoperatively (p = 0.09).

TABLE III Baseline demographics and tumour characteristics for 27 study patients


TABLE IV Outcomes for 27 study patients after treatment



The signal study represents a novel approach to the radiotherapeutic management of early-stage low-risk carcinoma of the breast. The classic approach for such patients, established over many decades, is surgery followed by rt. The benefit of adjuvant rt in such a setting is well known and so too are its toxicities. In principle, neoadjuvant rt holds several advantages over adjuvant rt, including improved tumour oxygenation, reduced dose to the surrounding normal tissues because of a smaller target volume, and of course the ability to recognize and to delineate the disease in situ. That latter benefit was of particular interest to us, given the availability of mri for radiation treatment planning with image co-registration. Hypofractionation is now established in the treatment of multiple malignancies. As sfrt, sbrt, and other hypofractionated techniques likewise become more established in the management of breast cancer, it is incumbent upon us to understand as fully as possible the potential benefits and toxicities of that approach.

The unique aspects of the signal trial include the use of volumetric arc therapy with strict dosimetry constraints to skin and normal tissues, avoiding any early skin erythema or dermatitis, and any delayed fibrosis or telangiectasias by latest follow-up at 1 year. The co-registration of prone breast imaging allowed for high-fidelity treatment delivery, minimizing the dose to skin which, if these low-risk patients had requested mastectomy, would not require radiation at all, but when radiated, contributes to worsened cosmetic outcome and patient satisfaction. High-fidelity treatment might explain why our cosmetic outcomes were better than those reported by Pinnaro et al.22 in their sfrt trial using intensity-modulated rt (59% of patients reporting a good or excellent cosmetic outcome), and similar or better than outcomes in other larger trials looking at cosmesis with more standard radiation regimens (in the range of 81%–95% reporting good or excellent cosmesis)17,20,23.

As a pilot study, signal’s primary endpoints were feasibility and safety. Our results suggested that sfrt, when delivered in the manner specified by signal, was certainly tolerable and well-liked by the patients. Our approach with the initial dosimetry constraints was not feasible, but it became feasible after revision of the conservative constraints, with successful treatment of all eligible patients in the revised cohort compared with only a proportion of the patients in the initial cohort. In the initial cohort, acceptable radiation treatment plans could not be generated for 12 patients who appeared eligible by breast mri. For those 12 patients, the primary reason for ineligibility was proximity of the gtv to the skin (8 patients) or chest wall (4 patients), thereby rendering it impossible to meet the study-defined dosimetry limits. We therefore realized that our limits were simply too restrictive and would limit generalizability of the trial to a breast cancer population commonly seen in practice. This difficulty was most obvious for skin. We initially defined skin as the external contour contracted isotropically by 5 mm; we likewise required that the ptv could not extend into the skin. In addition, we imposed a maximum point dose of 16 Gy to the skin. Such definitions severely limited our ability to devise an acceptable treatment plan for patients whose disease was located more than 2 cm away from the skin surface. The situation was even less tenable when the ptv was situated in areas in which the external breast contour was changing rapidly in three dimensions, such as in the retroareolar region, where the ptv was surrounded by “skin” on every side except posteriorly. In addition, for lesions located very medially, buildup of dose was less, necessitating delivery of a somewhat higher dose both superficially and also through the chest wall if the prescription dose were to be attained.

When we devised the original normal-tissue dosimetric limits for signal, we reviewed multiple published studies of sfrt11,17,21,24,25 and accelerated partial-breast irradiation26,27, delivered using a variety of techniques in both the preoperative and postoperative settings. Most of those studies did not state specific skin constraints, even though the primary toxicity in most cases appeared to be skin toxicity. Our original dosimetric limits were therefore chosen to be conservative, recognizing that the available clinical data at that dose–fractionation were limited. Our revised dosimetric criteria were based on re-review of the published literature and on our limited clinical experience gained up to that point. Once the dosimetric limits were revised, 100% of mri-eligible patients accrued to the study were successfully treated, which met our a priori feasibility threshold of 90%. We therefore feel that signal using the revised dosimetric constraints could be considered a feasible method of delivering single-dose neoadjuvant rt.

Our second primary endpoint was radiation toxicity, which is related to the secondary endpoints of cosmesis and qol, because changes to the skin and underlying soft tissue of the breast can be immediately visible as discolorations. The mean toxicity score was not significantly different from baseline at 3 weeks, 6 months, or 1 year postoperatively (Table IV). A few grade 1 postsurgical toxicities were reported (such as transient postsurgical thickening at the scar), and 1 patient experienced a grade 2 toxicity (delayed wound infection at 6 months postoperatively), representing an expected breast wound infection rate from surgery alone. Neither patient- nor physician-rated cosmesis changed significantly from baseline at 3 weeks or 6 months post-operatively (Table IV). Finally, patients reported significantly improved qol at 3 weeks compared with baseline, although qol returned to baseline by 6 months.

The main limitation of this single-arm study is the small sample size and relatively short follow-up. The signal trial was designed to inform the design of future prospective randomized clinical trials by determining overall feasibility, identifying any early concerns about toxicity and safety, and assessing patient interest. The study was certainly well received by our patients (only 1 of 53 patients declined participation). Once we identified workable dosimetry constraints, we were successful in treating patients in a very timely manner, something that was highly popular with our local patient population, given that many lived several hours away. Although acute toxicity and cosmesis were certainly acceptable, it is not possible to comment about late radiation toxicity; we simply have not followed our patients for a sufficiently long time to permit such an assessment. The determination of late radiation toxicity is especially relevant with sfrt, given that the estimation of equivalent radiobiologic effects at a higher dose per fraction is notoriously difficult. Nonetheless, we are satisfied with our selected dose (21 Gy in a single fraction) for several reasons. It was selected based on both the standard linear-quadratic formulation as well as on newer approaches such as the “universal survival curve” which models effects at high doses per fraction more accurately28. In addition, our selected dose is consistent with doses delivered in several similar studies11,17. Finally, the use of mri permitted very accurate definition of the gtv, and confinement of the prescription dose to the area targeted for excision likely reduced any significant effect on acute and delayed toxicity29. To ensure safety, we used very stringent criteria, including a requirement that lesions be at least 2 cm from the skin. To ensure accurate localization, we fused a breast mri for each patient. Furthermore, we moved to a prone setup to minimize the effect of respiratory motion and day-to-day setup of the breast. Those three components of our treatment are not readily available in all institutions and would limit generalizability. However, to maximize safety, to provide a sufficient dose, and to ensure reliability for this new technique, they were included. In most centres, those components could easily be adopted, and an assessment of the need for each one (especially mri) will be published separately.


Neoadjuvant single-fraction (21 Gy) partial-breast sbrt followed by breast-conserving surgery appears to be a feasible, safe, and well-tolerated method for delivering radiation in the prone position using external-beam rt and equipment available at standard rt facilities. The findings of the present study have to be confirmed in a prospective randomized clinical trial.


We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare that we have none.


*Department of Surgery, University of Toronto, Toronto, ON,
Division of Radiation Oncology, Department of Oncology, London Regional Cancer Program, London, ON,
Schulich School of Medicine and Dentistry, Western University, London, ON,
§London Tumour Biobank, St. Joseph’s Health Care, London, ON,
||Medical Physics, London Regional Cancer Program, London, ON,
#Department of Medical Imaging, St. Joseph’s Health Care, London, ON,
**Department of Radiation Medicine and Applied Sciences, School of Medicine, University of California–San Diego, San Diego, U.S.A.,
††Division of Surgical Oncology, Department of Surgery, London Health Sciences Centre, London, ON.


1 Fisher B, Redmond C, Poisson R, et al. Eight-year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med 1989;320:822–8. [Erratum in: N Engl J Med 1994;330:1467]
cross-ref  pubmed  

2 Veronesi U, Zucali R, Luini A. Local control and survival in early breast cancer: the Milan trial. Int J Radiat Oncol Biol Phys 1986;12:717–20.
cross-ref  pubmed  

3 Forrest AP, Strewart HJ, Everington D, et al. Randomised controlled trial of conservation therapy for breast cancer: 6-year analysis of the Scottish trial. Scottish Cancer Trials Breast Group. Lancet 1996;348:708–13.
cross-ref  pubmed  

4 Whelan TJ, Pignol JP, Levine MN, et al. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med 2010;362:513–20.
cross-ref  pubmed  

5 Agrawal RK, Alhasso A, Barrett-Lee PJ, et al. on behalf of the fast Trialists Group. First results of the randomized U.K. fast trial of radiotherapy hypofractionation for treatment of early breast cancer (cruke/04/015). Radiother Oncol 2011;100:93–100.
cross-ref  pubmed  

6 Holli K, Hietanen P, Saaristo R, Huhtala H, Hakama M, Joensuu H. Radiotherapy after segmental resection of breast cancer with favorable prognostic features: 12-year follow-up results of a randomized trial. J Clin Oncol 2009;27:927–32.

7 Haviland JS, Owen JR, Dewar JA, et al. The UK Standardisation of Breast Radiotherapy (start) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10- year follow-up results of two randomised controlled trials. Lancet Oncol 2013;14:1086–94.
cross-ref  pubmed  

8 Correa C, Harris EE, Leonardi MC, et al. Accelerated partial breast irradiation: executive summary for the update of an astro evidence-based consensus statement. Pract Radiat Oncol 2017;7:73–9.

9 Polgar C, Van Limbergen E, Potter R, et al. on behalf of the gecestro Breast Cancer Working Group. Patient selection for accelerated partial-breast irradiation (apbi) after breast-conserving surgery: recommendations of the Groupe Européen de Curiethérapie–European Society for Therapeutic Radiology and Oncology (gecestro) Breast Cancer Working Group based on clinical evidence (2009). Radiother Oncol 2010;94:264–73.

10 Veronesi U, Orecchia R, Maisonneuve P, et al. Intraoperative radiotherapy versus external radiotherapy for early breast cancer (eliot): a randomized controlled equivalence trial. Lancet Oncol 2013;14:1269–77.
cross-ref  pubmed  

11 Vaidya JS, Baum M, Tobias JS, et al. Long-term results of targeted intraoperative radiotherapy (Targit) boost during breast-conserving surgery. Int J Radiat Oncol Biol Phys 2011;81:1091–7.

12 Guidolin K, Lock M, Richard L, Boldt G, Brackstone M. Predicting which patients actually receive radiation following breast conserving therapy in Canadian populations. Can J Surg 2016;59:358–60.
cross-ref  pubmed  pmc  

13 Wang EH, Park HS, Rutter CE, et al. Association between access to accelerated partial breast irradiation and use of adjuvant radiotherapy. Cancer 2017;123:502–11.

14 Olivotto IA, Whelan TJ, Parpia S, et al. Interim cosmetic and toxicity results from rapid: a randomized trial of accelerated partial breast irradiation using three-dimensional conformal external beam radiation therapy. J Clin Oncol 2013;31:4038–45.
cross-ref  pubmed  

15 Guidolin K, Lock M, Yaremko B, et al. A phase ii trial to evaluate single-dose stereotactic body radiation therapy (sbrt) prior to surgery for early-stage breast carcinoma: signal (Stereotactic Image-Guided Neoadjuvant Ablative Radiation Then Lumpectomy) trial. J Radiat Oncol 2015;4:423–30.

16 Horton JK, Blitzblau RC, Yoo S, et al. Preoperative single-fraction partial breast radiation therapy: a novel phase 1, dose-escalation protocol and exploration of breast cancer radiation response. Int J Radiat Oncol Biol Phys 2015;92:846–55.
cross-ref  pubmed  pmc  

17 Pinnaro P, Arcangeli S, Giordano C, et al. Toxicity and cosmesis outcomes after single fraction partial breast irradiation in early stage breast cancer. Radiat Oncol 2011;6:155.
cross-ref  pubmed  pmc  

18 United States, Department of Health and Human Services, National Institutes of Health, National Cancer Institute (nci). Common Terminology Criteria for Adverse Events (CTCAE). Ver. 4.03. Bethesda, MD: nci; 2010.

19 Harris JR, Levene MB, Svensson G, Hellman S. Analysis of cosmetic results following primary radiation therapy for stages i and ii carcinoma of the breast. Int J Radiat Oncol Biol Phys 1979;5:257–61.
cross-ref  pubmed  

20 Brady MJ, Cella DF, Mo F, et al. Reliability and validity of the Functional Assessment of Cancer Therapy–Breast quality-of-life instrument. J Clin Oncol 1997;1:974–86.

21 Blitzblau RC, Arya R, Yoo S, et al. A phase 1 trial of preoperative partial breast radiation therapy: patient selection, target delineation, and dose delivery. Pract Radiat Oncol 2015;5:e513–20.
cross-ref  pubmed  pmc  

22 Pinnaro P, Giordano C, Farneti A, et al. Short course hypofractionated whole breast irradiation after conservative surgery: a single institution phase ii study. J Exp Clin Cancer Res 2017;36:191.

23 Sayan M, Hard D, Wilson K, et al. Long-term cosmesis following a novel schedule of accelerated partial breast radiation in selected early stage breast cancer: result of a prospective clinical trial. Radiat Oncol J 2017;35:325–31.
cross-ref  pubmed  pmc  

24 Veronesi U, Orecchia R, Luini A, et al. Intraoperative radiotherapy during breast conserving surgery: a study on 1,822 cases treated with electrons. Breast Cancer Res Treat 2010;124:141–51.
cross-ref  pubmed  

25 Hoppe BS, Laser B, Kowalski AV, et al. Acute skin toxicity following stereotactic body radiation therapy for stage i non-small- cell lung cancer: who’s at risk? Int J Radiat Oncol Biol Phys 2008;72:1283–6.
cross-ref  pubmed  

26 van der Leij F, Bosma SC, van de Vijver MJ, et al. First results of the preoperative accelerated partial breast irradiation (papbi) trial. Radiother Oncol 2015;114:322–7.
cross-ref  pubmed  

27 Formenti SC, Hsu H, Fenton-Kerimian M, et al. Prone accelerated partial breast irradiation after breast-conserving surgery: five-year results of 100 patients. Int J Radiat Oncol Biol Phys 2012;84:606–11.
cross-ref  pubmed  pmc  

28 Park C, Papiez L, Zhang S, Story M, Timmerman RD. Universal survival curve and single fraction equivalent dose: useful tools in understanding potency of ablative radiotherapy. Int J Radiat Oncol Biol Phys 2008;70:847–52.
cross-ref  pubmed  

29 Kurtz JM. The clinical radiobiology of breast cancer radiotherapy. Radiother Oncol 2005;75:6–8.
cross-ref  pubmed  

Correspondence to: Muriel Brackstone, 790 Commissioners Road East, London, Ontario N6A 4L6..E-mail:

(Return to Top)

Current Oncology, VOLUME 26, NUMBER 3, JUNE 2019

Copyright © 2019 Multimed Inc.
ISSN: 1198-0052 (Print) ISSN: 1718-7729 (Online)