Report on the Clinical Outcomes of Permanent Breast Seed Implant for Early-Stage Breast Cancers

doi:10.1016/j.ijrobp.2015.07.2266

International Journal of Radiation OncologyBiologyPhysics

Volume 93, Issue 3, 1 November 2015, Pages 614-621

https://doi.org/10.1016/j.ijrobp.2015.07.2266 Get rights and content

Purpose

Permanent breast seed implant is an accelerated partial breast irradiation technique realizing the insertion of ¹⁰³Pd seeds in the seroma after lumpectomy. We report the 5-year efficacy and tolerance for a cohort, pooling patients from 3 clinical trials.

Methods and Materials

The trials accrued postmenopausal patients with infiltrating ductal carcinoma or ductal carcinoma in situ ≤3 cm and clear surgical margins, who were node negative, and had a planning target volume <120 cm³. The outcomes included overall and disease-free survival and local and contralateral recurrence at 5 years. The true local recurrence rate was compared using 2-tailed paired t tests for estimates calculated using the Tufts University ipsilateral breast tumor recurrence and Memorial Sloan Kettering ductal carcinoma in situ nomograms.

Results

The cohort included 134 patients, and the observed local recurrence rate at a median follow-up period of 63 months was 1.2% ± 1.2%, similar to the estimate for whole breast irradiation (P=.23), significantly better than for surgery alone (relative risk 0.27; P<.001), and significantly lower than contralateral recurrence (relative risk 0.33; P<.001). The 5-year overall survival rate was 97.4% ± 1.9%, and the disease-free survival rate was 96.4% ± 2.1%. At 2 months, 42% of the patients had erythema, 20% induration, and 16% moist desquamation. The rate of mainly grade 1 telangiectasia was 22.4% at 2 years and 24% at 5 years. The rate of asymptomatic induration was 23% at 2 years and 40% at 5 years.

Conclusions

The 5-year data suggest that permanent breast seed implantation is a safe accelerated partial breast irradiation option after lumpectomy for early-stage breast cancer with a tolerance profile similar to that of whole breast irradiation.

Introduction

Most breast cancers are diagnosed at an early stage 1, 2, and the current standard of care includes breast-conserving surgery with limited node sampling, followed by whole breast irradiation (WBI) delivered 5 days per week for 3 to 7 weeks 3, 4, 5. For appropriately selected patients, limiting radiation to the postoperative cavity with a margin can suffice to prevent local recurrence 6, 7, 8, 9. Also, because a smaller volume of normal tissue is treated, the radiation therapy can be delivered within a shorter period 8, 9. The concept of accelerated partial breast irradiation (APBI) has been tested in multiple studies, including phase 3 trials 10, 11, 12, 13, and diverse techniques have been proposed, including brachytherapy, external beam 3-dimensional conformal radiation therapy, and intraoperative radiation therapy 11, 12, 13. The American Society for Radiation Oncology and several other societies have published recommendations for the careful use of APBI 14, 15, 16, 17.

In 2006, our team reported the first use of permanent breast seed implant (PBSI) as a technique for APBI (18). Patients have been enrolled in 3 consecutive pilot or registry trials. Thus, in the present study, we performed a post hoc analysis of the 5-year efficacy and tolerance for a cohort of patients accrued in those trials. The results were compared with the calculated probability of local control using the Tuft University ipsilateral breast tumor recurrence (IBTR) invasive carcinoma nomogram and the Memorial Sloan Kettering Cancer Center ductal carcinoma in situ (DCIS) recurrence nomogram 19, 20.

Section snippets

Patients

The first phase 1/2 study included patients aged ≥40 years who had undergone lumpectomy for unifocal infiltrating ductal carcinoma, grade 1 or 2, <3 cm in diameter, with surgical margins of ≥5 mm, no lymphovascular invasion, and <25% DCIS. Lobular histologic features were excluded. Initially, patients with 1 to 3 positive nodes were included; however, after the publication of the American Society for Radiation Oncology guidelines (14), such patients were also excluded. The endpoints were local

Patients, date, and census

From April 2004 to May 2014, 134 patients were treated in the 3 studies and in 3 centers by 4 radiation oncologists. The initial phase 1/2 study accrued 67 patients from April 2004 to April 2007. A 2-year gap separated the first and the second 2 subsequent studies to collect the efficacy, tolerance, and safety PBSI data. The 2 subsequent multicenter studies also accrued 67 patients from April 2009 to May 2014. Only patients with a minimum 6-month follow-up period were selected for the present

Discussion

The present study reports on the 5-year outcomes of patients with early-stage breast cancer treated with PBSI as the sole form of adjuvant radiation therapy. The efficacy appeared similar to that of WBI, with a 5-year local recurrence rate similar to that predicted by nomograms, 1.2% versus 1.4% (P=NS). This rate of local recurrence is one quarter of that estimated for patients treated with lumpectomy without radiation therapy (4.6%; P<.001) and one third of that calculated for contralateral

Conclusions

The role of APBI is still pending the final results of several multicenter randomized controlled trials in Europe, the United States, and Canada (11). The purpose of the present study was to assess the value of seed brachytherapy as a form of APBI. The results we have reported suggest that the technique is safe and the tolerance is equivalent to that of other APBI brachytherapy techniques.

Acknowledgments

This research was supported by the Canadian Breast Cancer Foundation, Ontario Chapter.

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Cited by (50)

A postimplant dosimetry simulation framework for robustness evaluation in permanent breast seed implant brachytherapy
2024, Brachytherapy
Permanent breast seed implant (PBSI) brachytherapy is a promising treatment that has the potential to be widely utilized with increased standardization, optimization, and robustness. Excellent early efficacy and very high patient acceptance were reported, however, to further evaluate and improve planning strategies, a framework to quantify plan robustness to implant uncertainties is necessary.
In this study, we aim to quantify clinical seed displacement using an automated algorithm and develop and validate a PBSI post-implant dosimetry simulation framework to evaluate PBSI plan robustness to implant uncertainties.
Clinical PBSI seed displacements were quantified for 63 consecutive patients. A PBSI simulator was developed in Matlab (2020) by resampling clinical seed displacements and computing a range of possible post-implant dosimetry outcomes under various seed displacement scenarios. Simulations were performed retrospectively on 63 previous clinical plans to evaluate plan robustness to seed displacement.
Mean seed displacement for the whole cohort was 10 ± 6 mm. A clinical seed displacement database was established and a user interface was developed for the simulation framework. For all clinical plans, the median (range) value of simulated median ETV V90 in various seed displacement scenarios was 97.8% (87.5–100%).
A PBSI postimplant dosimetry simulation framework was developed and validated. Simulation results showed that the current PTV planning margin is sufficient to provide adequate postimplant dose coverage of ETV. This simulator can be used to evaluate plan robustness to seed displacement and will facilitate future research in improving PBSI planning methods.
Special issue. De-escalation of loco-regional treatment in breast cancer: Time to find the balance? Partial breast irradiation
2023, Breast
Breast cancer is the most common cancer in women worldwide. Over the past few decades, remarkable progress has been made in understanding the biology and pathology of breast cancer. A personalized conservative approach has been currently adopted addressing the patient's individual risk of relapse. After postoperative whole breast irradiation for early-stage breast cancer, a rate of recurrences outside the initial tumour bed lower than 4% was observed. Thus, the highest benefits of breast irradiation seem to result from the dose delivered to the tissue neighbouring the tumour bed. Nonetheless, reducing treatment morbidity while maintaining radiation therapy's ability to decrease local recurrences is an important challenge in treating patients with radiation therapy. In this regard, strategies such as partial-breast irradiation have been developed to reduce toxicity without compromising oncologic outcomes. According to the national and international published guidelines, clinical oncologists can refer to specific dose/fractionation schedules and eligible criteria. However, there are still some areas of open questions. Breast cancer represents a multidisciplinary paradigm; it should be considered a heterogeneous disease where a “one-treatment-fits-all” approach cannot be considered an appropriate option. This is a wide overview on the main partial breast irradiation advantages, risks, timings, techniques, and available recommendations. We aim to provide practical findings to support clinical decision-making, exploring future perspectives, towards a balance for optimisation of breast cancer.
Breast brachytherapy: Building a bright future on the foundation of a rich history of advancement in technology, technique, and patient-centered care
2023, Brachytherapy
For over 20 years, the concept of accelerated partial breast irradiation (APBI) has received considerable attention. Initially concentrating on the appropriateness of APBI as an alternative treatment to whole breast radiotherapy, investigation and innovation evolved towards dose delivery and technique appropriateness. The purpose of this article is to review the pertinent literature that supports the role brachytherapy serves in delivering APBI and the recognized brachytherapy techniques for dose delivery. Publications establishing techniques utilizing multicatheter brachytherapy, single-entry brachytherapy applicators, permanent breast seed implantation brachytherapy, noninvasive breast brachytherapy and electronic brachytherapy are described. The use of brachytherapy for repeat breast conservation therapy is additionally reviewed. A historical perspective and potential direction of future investigation and innovation are presented.
Feasibility study of defining planning target volume using surgical margins in permanent breast seed implant brachytherapy
2023, Brachytherapy
This study investigates the feasibility and potential impacts of utilizing a Groupe Européen de Curiethérapie-European Society for Therapeutic Radiation and Oncology (GEC ESTRO) recommended surgical margin-based planning margin in permanent breast seed implant (PBSI) brachytherapy.
Seventy-nine patients were included in this retrospective study. Three margin selections were used for PTV construction: (1) 1.25 or 1.5 cm isotropic margin (PTV_PBSI), (2) 2 cm minus surgical margin in each direction as recommended by GEC ESTRO (PTV_aniso), and (3) 2 cm minus minimum surgical margin isotropically (PTV_iso). PTV volume and dose coverage using clinical PBSI plans were compared across three groups. New PBSI plans were constructed on PTV_aniso for 20 patients and planning parameters were compared to original plans constructed on PTV_PBSI.
Twenty patients had surgical margins in six directions reported, with a median value of 8 mm anteriorly, and 10 mm in all other directions. PTV_aniso (36.3 ± 15.0 cc) was overall smaller than PTV_PBSI (55.6 ± 14.3 cc), p value < 0.05. PBSI clinical plans showed satisfactory coverage on PTV_aniso, with a median (range) V100 of 97.9% (85.8%–100.0%). Comparing to original treatment plans, new plans constructed on PTV_aniso reduced the number of implant seeds and skin dose.
Clinical PBSI plans provide satisfactory coverage of GEC ESTRO recommended PTVs. In this patient cohort, GEC ESTRO planning margin resulted in smaller target volumes, and therefore, new plans constructed on PTV_aniso required fewer implanted seeds and lower skin doses were achieved. However, given PBSI delivery uncertainties, further investigations are required to determine if the GEC ESTRO planning margin will be sufficiently robust.
Partial breast irradiation: An updated consensus statement from the American brachytherapy society
2022, Brachytherapy
In 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.
Members 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.
The 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.
This 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.
Comparison of visibility of iodinated hydrogel and gadolinium-modified hyaluronic acid spacer gels on computed tomography and onboard imaging
2022, Physics and Imaging in Radiation Oncology
Citation Excerpt :
It reduces the amount of tissue irradiated and helps to reduce the amount of radiation scattered to the body, possibly providing a survival advantage in reducing the risk of death from secondary cancers [8]. For well selected low-risk patients, large multicenter randomized clinical trials have shown equivalent oncological outcomes for whole breast irradiation and APBI using brachytherapy [9–11], external 3D conformal radiotherapy [12,13], and intraoperative therapy [14,15]. APBI requires accurate target delineation for treatment planning, as well as a precise target localization during treatment since a geographical miss can lead to an increased risk of local recurrence and toxicity.
In accelerated partial breast irradiation (APBI), accurate definition of the tumour bed is crucial to reduce the risk of local recurrence and the volume of healthy tissue irradiated. Recently, hydrogels have been proposed to improve visibility of the lumpectomy cavity for APBI. The aim of this study was to alter two commercially available hyaluronic acid (HA) gels, with gadopentenate dimeglumine (GD), a magnetic resonance imaging (MRI) contrast agent. We hypothesize that after injection in the surgical cavity, the mixtures will be visible with computed tomography (CT) for improved treatment planning, cone-beam CT (CBCT) for improved patient setup and planar kilovoltage (kV) x-ray for real-time tracking during treatment.
In this ex vivo study, GD was mixed with the two HA gels, and 1 mL of each mixture was injected into fatty and muscular tissue of a pork phantom. Visibility with CT, CBCT and planar x-ray imaging was assessed. Contrast-to-noise ratios (CNR) were measured and compared to commercially available iodinated polyethylene glycol (PEG).
The gel mixtures showed increased visibility over HA gels without GD. When comparing CNR of the gel mixtures to that of iodinated PEG on CT, there was a 4-fold increase in muscle for both mixtures and a 1.6-fold to 3.6-fold increase in fat, depending on the HA gel. Gel mixtures showed better visibility with planar kV imaging over iodinated PEG.
Addition of GD to HA gels increases visibility with CT, CBCT and planar x-ray imaging, indicating potential for improved delineation and positioning in APBI.

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Clinical InvestigationReport on the Clinical Outcomes of Permanent Breast Seed Implant for Early-Stage Breast Cancers

Purpose

Methods and Materials

Results

Conclusions

Introduction

Section snippets

Patients

Patients, date, and census

Discussion

Conclusions

Acknowledgments

Lancet

Lancet

J Am Coll Surg

Radiother Oncol

Lancet

Int J Radiat Oncol Biol Phys

Radiother Oncol

Brachytherapy

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Semin Radiat Oncol

Lancet Oncol

Int J Radiat Oncol Biol Phys

J Am Coll Surg

Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: Meta-analysis of individual patient data for 10,801 women in 17 randomised trials

Lancet

Clinical Investigation
Report on the Clinical Outcomes of Permanent Breast Seed Implant for Early-Stage Breast Cancers