Partial Breast Re-irradiation Research Articles

Hypofractionated partial breast re-irradiation in the conservative retreatment of breast cancer local recurrence

Aimto evaluate the outcome of partial breast re-irradiation (re-PBI) with intensity modulated RT (IMRT), using a hypofractionated scheme for breast cancer (BC) local recurrence (LR) operated on with repeat breast-conserving surgery (re-BCS). MethodsIMRT-based re-PBI was performed using either helical or step-and-shoot modality to deliver 37.05 Gy in 13 fractions in 2.5 weeks. Cumulative incidence (CumI) of 2ndLR, toxicity, disease-free (DFS), BC specific (BCSS), and overall (OS) survival were evaluated. ResultsBetween 5/2012 and 5/2021, 70 patients had re-PBI. Median follow-up (FU) was 6.3 years (Q1-Q3, 4.0-8.1.). Median age at 1stLR was 62. The median primary BC-1stLR interval was 12.4 years (range: 1.6-26.7). Luminal A-like 1stLR accounted for 41% of the cases and median size was 0.8 cm. During FU, 18 (26%) patients showed a subsequent event: three 2snLRs (corresponding to 8-y Cumulative rate of 4%), 3 regional nodal recurrences, 7 distant metastases, and 5 other primary tumors. At 8 years, DFS, BCSS and OS were 76%, 90%, and 90%, respectively. At multivariate analysis, Grade 3 and extensive intraductal component were independent predictors for DFS. For 51 and 46 patients, chronic toxicity and cosmesis were evaluated, respectively: 4% had grade 3 fibrosis and cosmesis was deemed good/excellent in just over 60% of the cases. ConclusionRe-PBI after re-BCS represents a feasible alternative to mastectomy with regard to local control, showing an acceptable toxicity profile. A long-term FU is crucial to better understand the pattern of relapse and consolidate the position of re-PBI in clinical practice

Salvage Breast-Conserving Surgery and Reirradiation With Intraoperative Electrons for Recurrent Breast Cancer: A Multicentric Study on Behalf of Italian Association of Radiotherapy and Clinical Oncology

AimIntraoperative radiotherapy with electrons (IOERT) may represent a viable choice for partial breast re-irradiation (rePBI) after repeat quadrantectomy for local recurrence (LR) for primary breast cancer (BC) in lieu of mastectomy. Materials and MethodsA database collecting data on rePBI with IOERT from 8 Italian centres was set up in 2016- 2018, providing data on cumulative incidence (CumI) of 2nd LR nd survival with a long follow-up (FU) ResultsFrom 2002 to 2015, 109 patients underwent the conservative retreatment.The median primary BC -1stLR interval was 11.1 years (range: 2.4-27.7). The median 1stLR size was 0.9 cm (range: 0.3-3.0) and 43.6% were Luminal A. Median IOERT dose was 18 Gy (range: 12-21) and median collimator was 4 cm (range: 3-6). Median FU was 11.7 years (interquartile range: 7.7-14.6). The 2ndLR CumI was 12.2% (95% CI: 6.8-19.2) at 5 years and 32.3% at 10 years (95% CI: 22.8-42.2), occurring in the same site as the 1stLR in about half of the cases. HER2 status and collimator size were independent LR predictors. The 5- and 10-year overall survival were 95.2% and 88.3%, respectively, while 5- and 10-year BC specific survival were 98% and 94.5%. The development of a 2ndLR significantly reduced BCSS (HR=9.40, P<0.001). Grade ≥3 fibrosis was 18.9%. Patient-reported cosmesis was good/excellent in 59.7% of the cases. Conclusion2ndLR CumI was within the range of the literature, but higher than expected, opening questions on radiation field extension and fractionation schedule. Since a 2ndLR worsened the outcome, salvage modality must be carefully planned.

Second Conservative Treatment for Local Recurrence Breast Cancer: A GEC-ESTRO Oncological Outcome and Prognostic Factor Analysis

For second ipsilateral breast tumor event (2nd IBTE), second conservative treatment (2nd CT) combining lumpectomy plus accelerated partial breast reirradiation (APBrI) represents a curative option. The aim of this study was to analyze oncological prognostic factors for patients with a 2nd IBTE treated with 2nd CT. An analysis of clinical practices was conducted across 7 academic hospitals/cancer centers in 6 European countries based on the GEC-ESTRO database. Patients presenting a 2nd IBTE occurring after conservative surgery (lumpectomy+axillary evaluation) and irradiation performed for the primary tumor underwent a 2nd CT with brachytherapy-based APBrI. The main outcome was 5-year cumulative incidence (CI) rate of second local relapse. All analyzed patients were classified according to risk groups for Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) accelerated partial breast irradiation (APBI) and molecular classification and time interval between first and second breast surgery (TIS1S2). Finally, we combined GEC-ESTRO APBI, molecular, and TIS1S2 risk groups, leading to the definition of a new score (named TAM: score based on the combination of time interval [T] between first and second surgery and APBI [A] and molecular [M] classifications) specifically designed for 2nd IBTE oncological outcome analysis. From July 1994 to January 2021, a total of 508 patients received a 2nd CT. At the time of 2nd IBTE, median age was 64.6 years (range, 56.2-72.6). With a median follow-up of 60.9 months (56.2-72.6), the 5-year second local relapse CI rate was 4% (95% confidence interval [95% CI], 2%-6%). The 5-year distant metastasis disease CI rate was 7% (95% CI, 4%-10%). Five-year disease-free and overall survival rates were 89% (95% CI, 86%-93%) and 91% (95% CI, 88%-94%), respectively. In multivariate analysis, TAM score was an independent prognostic factor for all the oncological items (P < .001) except disease-specific survival (P=.07) and overall survival (P=.09). The grade ≥3 late toxicity rate was 12.1%. This analysis of 2nd CT combining lumpectomy with APBrI for 2nd IBTE confirmed the excellent oncological results obtained after 2nd CT. Furthermore, the GEC-ESTRO TAM score appears to be an important prognostic factor, assisting patients and physicians in the decision-making process.

PO-1251 Partial breast re-irradiation with IMRT for local recurrence after whole breast radiotherapy

PO-1251 Partial breast re-irradiation with IMRT for local recurrence after whole breast radiotherapy

PL02 Presentation Time: 2:15 PM: Protocol-Based Re-Lumpectomy and Salvage Brachytherapy as Accelerated Partial Breast Re-Irradiation for In-Breast Tumor Recurrence After Whole Breast Irradiation: Long-Term Results

<h3>Purpose</h3> To analyze the clinical outcome of salvage lumpectomy and multi-catheter salvage brachytherapy for local recurrent breast tumor. <h3>Material and Methods</h3> Between 07/03 and 12/21, 76 patients with local recurrence after previous breast conserving surgery and whole breast irradiation underwent a protocol based re-lumpectomy and adjuvant salvage-brachytherapy as partial breast re-irradiation. We analyzed second local recurrent rates, distant metastasis rates, disease-free survival, and overall survival as primary objective, and late effects and cosmetic results as secondary objective. <h3>Results</h3> Median and mean follow-up after the salvage brachytherapy was 48 and 65 months, respectively [range: 8-198 months]. The 5y.- and 10y.-cumulative local 2^nd recurrence rates were 4.1% and 17.1%, respectively. Five and 10-year actuarial distant-metastasis rate were 7.7%. 5y.- and 10-year overall survival rates were 90.8% and 85.4%, respectively. As serious late side effects grade 3-4 we observed only fibrosis grade 3 by 8/76 patients (10.5%). <h3>Conclusion</h3> For patients with local in-breast recurrence after previous breast conserving surgery and whole breast irradiation is the re-lumpectomy plus salvage-brachytherapy as partial breast re-irradiation a reasonable and effective organ sparing treatment option, which is at least equivalent to results achieved with salvage mastectomy.

Changes in Fractionation Schedules for Breast Cancer Treatment during the COVID-19 Pandemic

Purpose/Objective(s)In 2020, 5-year results of the FAST-Forward trial and 10-year results for both the FAST trial and APBI-IMRT-Florence trials using ultrahypofractionated radiation (UHFR) were all published, each detailing equivalent outcomes for partial and whole breast UHFR schedules compared to more conventional fractionation regimes in early-stage breast cancer. Due to concerns over viral exposure, these treatment regimens were adopted in an effort to minimize patient exposure while achieving equivalent oncologic control. The purpose of this study was to compare the use of UHFR schedules for breast cancer patients before COVID-19, at the height of the pandemic and after widespread vaccination and analyze factors predictive of use.Materials/MethodsBetween October 2019 and February 2022, 733 patients with stage 0 or I breast cancer were offered radiation at our institution following breast conserving surgery. 43 patients were excluded (35 declined radiation and 8 received partial breast re-irradiation). We analyzed target volume (whole vs partial breast) and fractionation schemes (1 week vs 3 or more weeks) for 3 time periods of interest: pre-COVID-19 (October 2019-March 2020), height of COVID-19 (March 2020-March 2021) and post-COVID-19 vaccine (March 2021-February 2022). Fisher's exact test was used to compare frequencies of treatment parameters across groups and time periods. Logistic regression was used to determine factors associated with UHFR use. R (v4.1.2) was used for analysis.ResultsThe use of UHFR increased during the post-vaccine period as compared to pre-Covid-19 and the pre-vaccine time periods (p<0.001), with 4.6%, 9.2% and 23%, receiving UHFR respectively. On univariate analysis in the pre-vaccine time period, patients with grade 2 and 3 cancers were less likely to get UHFR (p = 0.003 and p = 0.005, respectively). Receiving radiation from an academic attending was associated with higher use of UHFR (p = 0.0004). On multivariate (MVA) patients with grade 2 and 3 disease remained less likely to get UHFR (p 0.001 and 0.004). Treatment by an academic attending remained a significant factor for use of UHFR (p=0.0003). In the post-vaccine time period, on univariate analysis, negative ER status and grade 3 tumors were associated with less use of UHFR (p = 0.04 and p = 0.0001, respectively). On MVA, only grade 3 was associated with less UHFR use (p = 0.0002).ConclusionDuring COVID there was a significant increase in the use of UHFR regimens for treatment of early-stage breast cancer patients at our institution that persisted and increased after the introduction of the vaccine despite return to pre-COVID patient volumes. Uptake of these new regimens was initially higher among academic radiation oncologists, however with education of community physicians and implementation of treatment planning scorecards, widespread adoption was seen.

Partial Breast Reirradiation for Patients With Ipsilateral Breast Tumor Recurrence After Initial Treatment With Breast Conservation for Early Stage Breast Cancer

PurposeAccelerated partial breast irradiation (APBI), including intraoperative radiation therapy (IORT), is an evidence-based treatment option in patients undergoing breast conserving surgery (BCS) for early-stage breast cancer. However, literature regarding reirradiation for patients with ipsilateral breast tumor recurrences (IBTR) is limited. This prospective study assessed the feasibility and efficacy of using APBI in patients who had prior whole breast irradiation. Methods and MaterialsThis was a single institution, prospective study of patients who were previously treated with BCS and adjuvant whole breast radiation. At the time of enrollment, all had unifocal IBTR, histologically confirmed invasive ductal carcinoma with negative margins after repeat BCS. Patients received either IORT in a single fraction at time of BCS or MammoSite brachytherapy twice daily over 5 days. Follow-up data and patient surveys were collected at 1, 3, 6, 9, and 12 months, then annually for at least a 5-year period. ResultsFrom 2008 to 2014, 13 patients were enrolled. Median time to recurrence after initial course of radiation was 12.5 years. Median follow-up after retreatment was 7.8 years. One patient in the IORT group had a subsequent tumor bed recurrence, yielding a local control of 92%. One patient had distant recurrence. At baseline, 680 reported excellent-good cosmesis compared with 42% at 5 years. All patients indicated total satisfaction with overall treatment experience. ConclusionsAPBI using IORT was well tolerated with excellent local control and may be a reasonable alternative to mastectomy for IBTR. Further study is needed to determine the most suitable candidates for this approach.

Abstract PD7-09: Safety of conservative surgery with accelerated partial breast re-irradiation for isolated ipsilateral breast cancer recurrence regardless of immunohistochemical subtype. A multicentric prospective study

Abstract Background. The standard of care for patients (pts) with an ipsilateral breast tumour recurrence (IBTR) after breast conserving therapy (BCT) is a salvage mastectomy. However there is no solid data providing a clear advantage of radical surgery for IBTR in terms of the outcome for patients with isolated local recurrence after BCT. Nevertheless, there is a growing interest in the feasibility of repeating BCT for these patients (pts). We analyzed the oncological outcomes of repeated breast-conserving therapy (rBCT) related to the immunohistochemical subtype. Materials and methods. Between 2014 and 2020, 35 pts were selected for a 2nd BCT, a new lumpectomy with accelerated partial breast re-irradiation (APBrI), and prospectively followed in three university hospitals in Barcelona. Inclusion criteria were pts older than 50y with a late (&amp;gt; 48m from primary treatment) isolated IBTR less than 2cm, without having primary major radiotherapy toxicity. Oncological outcomes were analyzed. Results. At IBTR, median age was 65y and median time to ITBR was 154m. Patients characteristics are shown in table 1. Tumor’s recurrence was DCIS in 5 pts (14.3%) and invasive carcinoma in 30 pts (85.7%), where Luminal A in 10 pts (33.3%), Luminal B-HER2 negative in 12 pts (40%), Luminal B-HER2 positive in 2 (6.7%), non-Luminal HER2 positive in 3 (10%) and triple negative in 3 (10%). With a median follow-up of 37 months, there were 4 relapses (11.4%), one was a 2nd IBTR (2.85%) after in-situ IBTR, and 3 were metastatic recurrences (8.6%), two after invasive and one after in-situ IBTR. Both metastatic progressions after invasive IBTR, were hormone receptor positive and HER2 negative (Luminal B). There were 2 deaths not related with breast cancer. The 2nd IBTR rate was 2.85%. Five-year regional-free survival, metastasis-free survival, and overall survival was 82.4% (95% IC 52.6 - 94.4 %), %, 84.6% (95% IC 51 - 96 %) and 93.3% (95% IC 61.2 - 99%), respectively. Conclusion. Conservative treatment with breast conserving surgery and APBrI for isolated IBTR after BCT seems like a feasible technique as an alternative to mastectomy in selected patients. Second local recurrences and overall survival are similar to the rates described for salvage mastectomy for isolated ipsilateral breast tumour recurrence. In this cohort of patients, the immunohistochemical subtype tumors with poor prognosis (HER2 positive and triple negative) did not show increase in the local recurrence rate. Table 1.Patients Characteristicsn%Histology TypeIDC2777.1ILC0DCIS514.3Others38.6Differentiation gradeWell differentiated1028.6Moderately differentiated1851.4Poorly differentiated720Estrogen-receptor statusPositive2880Negative720Progesteron-receptor statusPositive1645.7Negative1748.6Unknown25.7HER2 statusOver-expressed617.1Non-over-expressed2674.3Unknown38.6Ki67&amp;lt; 20 %1748.6&amp;gt; 20 %1337.2Unknown514.3IHC subtypeLuminal A1033.3Luminal B1240Luminal B-HER2 positive26.7Non-luminal HER2 positive310Triple negative310IBTR locatedSame quadrant1748.6Different quadrant1645.7Unknwon25.7APBrI3D-CRT927.3IORT26.1IMRT2266.7 Citation Format: Martin Espinosa-Bravo, Victoria Reyes Lopez, Clara Morales Comas, Joaquín Rivero Déniz, Javier de La Torre Fernández de Vega, Irene Vives Roselló, Christian Sisó Raber, Manuel Altabas Gonzalez, Alexandra Giraldo Marin, Inma Alonso, Nuria Argudo, Pau Nicolau, Manel Algara, Xavier Sanz, Xavier Caparrós, Gabriela Oses, Jordi Saez, María Vernet-Tomas, Meritxell Mollà. Safety of conservative surgery with accelerated partial breast re-irradiation for isolated ipsilateral breast cancer recurrence regardless of immunohistochemical subtype. A multicentric prospective study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD7-09.

Salvage of locally recurrent breast cancer with repeat breast conservation using 45Gy hyperfractionated partial breast re-irradiation.

Mastectomy has long been the preferred approach for local salvage of recurrent breast cancer following breast-conservation therapy (BCT). Growing interest in avoiding mastectomy prompted RTOG 1014, a landmark phase two study demonstrating the feasibility of repeat BCT using a novel radiotherapy (RT) regimen (i.e., 45Gy administered in 30 fractions of 1.5Gy twice-daily to the partial breast, "rePBI"). We adopted this regimen as our institutional standard and report our observations regarding the safety and efficacy of rePBI as salvage therapy. All patients at our institution who underwent repeat BCT and subsequently received rePBI from 2011 to 2019 were identified. Clinicopathologic features and treatment characteristics for both primary breast cancers and recurrences were collected, as were rates of subsequent recurrence and treatment-associated toxicities. The cohort included 34 patients with a median age of 65.8 (46.2-78.2) at the time of rePBI. At a median follow-up of 23.5months, there were two subsequent locoregional recurrences (2-year local control rate 97%). There was no grade ≥ 3 toxicity. The most common acute toxicity (< 3months) was radiation dermatitis (100%), and common grade 1-2 late toxicities (> 3months) included fibrosis in 14 (41%), breast asymmetry in 12 (35%), and chest wall pain in 11 (32%). Repeat breast conservation using the hyperfractionated partial breast RT regimen defined by RTOG 1014 (45Gy administered in 30 1.5Gy twice-daily fractions) appears effective and well tolerated. No grade 3 or higher toxicities were observed and local control was excellent. Longer term follow-up among larger cohorts will define whether salvage mastectomy should remain the preferred standard.

Repeat breast-conserving treatment of ipsilateral breast cancer recurrence: a nationwide survey amongst breast surgeons and radiation oncologists in the Netherlands

BackgroundIn line with the paradigm to minimize surgical morbidity in patients with primary breast cancer, there is increasing evidence for the safety of a repeat breast-conserving treatment (BCT) of an ipsilateral breast tumour recurrence (IBTR) in selected patients. The conditions for the feasibility of a repeat BCT vary widely in literature. In clinical practice, many physicians have ongoing concerns about the oncological safety and possible toxicity of repeat BCT.AimTo investigate the attitude of Dutch breast surgeons and radiation oncologists towards repeat BCT and to report on their experiences with, objections against and perceived requirements to consider a repeat BCT in case of IBTR.Patients and methodsAn online survey consisting of a maximum of 26 open and multiple-choice questions about repeat BCT for IBTR was distributed amongst Dutch breast surgeons and radiation oncologists.ResultsForty-nine surgeons representing 49% of Dutch hospitals and 20 radiation oncologists representing 70% of Dutch radiation oncology centres responded. A repeat BCT was considered feasible in selected cases by 28.7% of breast surgeons and 55% of radiation oncologists. The most important factors to consider a repeat BCT for both groups were the patient’s preference to preserve the breast and surgical feasibility of a second lumpectomy. Arguments against a repeat BCT were based on the perceived unacceptable toxicity and cosmesis of a second course of radiotherapy. The technique of preference for re-irradiation would be partial breast irradiation (PBI) according to all radiation oncologists. Differentiating between new primary tumours (NPT) and true recurrences (TR) was reported to be done by 57.1% of breast surgeons and 60% of radiation oncologists. The most important reason to differentiate between NPT and TR was to establish prognosis and to consider whether a repeat BCT would be feasible.ConclusionAn increasing number of Dutch breast cancer specialists is considering a repeat BCT feasible in selected cases, at the patient’s preference and with partial breast re-irradiation.

PO-0937: Partial breast re-irradiation with IMRT for local recurrence after whole breast radiotherapy

PO-0937: Partial breast re-irradiation with IMRT for local recurrence after whole breast radiotherapy

Salvage of Locally Recurrent Breast Cancer with Repeat Breast Conservation Using 45Gy Hyperfractionated Partial Breast Re-Irradiation

Mastectomy has long been the preferred approach for local salvage of recurrent breast cancer following breast conservation therapy (BCT). Growing interest in avoiding mastectomy prompted RTOG 1014, a landmark phase 2 study demonstrating the feasibility of repeat BCT using a novel radiotherapy (RT) regimen (i.e. 45Gy administered in thirty fractions of 1.5Gy twice-daily to the partial breast, “rePBI”). We adopted this regimen as our institutional standard and report our experience to test the hypothesis that rePBI is safe and effective as salvage therapy. All patients at our institution who underwent repeat BCT from 2011-2019 were identified. Patients with invasive or in situ breast cancer who received rePBI were included. Clinicopathologic features and treatment characteristics for both primary breast cancers and recurrences were collected, as were rates of subsequent recurrence and treatment-associated toxicities. The cohort included 34 patients with a median age of 65.8 years (range 46.2 – 78.2) at the time of rePBI. At initial BCT, 12 (35%) had in-situ disease and 22 (65%) had invasive breast cancer with a median tumor size of 1. 2 cm (range 0.2 – 4.2 cm). Median whole breast RT dose was 48.6 Gy (range 42.4 – 54 Gy) and 27 (79%) received a boost to the lumpectomy cavity. At the time of local recurrence and salvage with BCT using rePBI, 9 (27%) patients presented with in-situ disease and 25 (73%) had invasive histology of which 28 (82%) were ER+, 19 (56%) were PR+, and 2 (6%) were HER2+. The median disease-free interval between primary and recurrence was 9.8 years (range 1.4-27.2) and median tumor size was 0.8 cm (range 0.1 – 3.5 cm). As part of the salvage regimen, 19 (56%) patients received endocrine therapy and 9 (27%) received chemotherapy or targeted therapy. At a median follow-up after rePBI of 23.5 months, there were two subsequent locoregional recurrences: one patient had another in-breast recurrence and underwent mastectomy (the only mastectomy in the cohort to date), the second patient had a regional recurrence and underwent axillary dissection followed by regional nodal irradiation. The overall rate of adverse events was low, with no grade ≥3 toxicity. The most common acute toxicity (< 3 months) was radiation dermatitis of grade 1 or 2, experienced by all patients. Late toxicities (> 3 months) included grade 1 or 2 fibrosis in 14 (41%), breast asymmetry in 12 (35%), chest wall pain in 11 (32%), lymphedema in 4 (12%), shoulder range of motion limitation in 3 (9%) and telangiectasia in 2 (6%). Repeat breast conservation using the hyperfractionated partial-breast RT regimen defined by RTOG 1014 (45Gy administered in thirty 1.5Gy twice-daily fractions) appears effective and well-tolerated. None of the patients in this cohort exhibited grade 3 or higher toxicity and subsequent local control was excellent. Longer term follow-up among larger cohorts will define whether salvage mastectomy should remain the preferred standard.

High-dose-rate Brachytherapy as Adjuvant Local rEirradiation for Salvage Treatment of Recurrent breAst cancer (BALESTRA): a retrospective mono-institutional study.

PurposeTo evaluate clinical results of catheter-based interstitial high-dose-rate (HDR) brachytherapy (BT) as adjuvant treatment in previously irradiated recurrent breast cancer.Material and methodsBetween January 2011 and September 2015, 31 consecutive patients with histologically confirmed recurrent breast cancer after conservative surgery and conventional whole breast radiotherapy, were retreated with a second conservative surgical resection and reirradiated with adjuvant interstitial HDR-BT. None of the brachytherapy implant was performed during the quadrantectomy procedure. A dose of 34 Gy in 10 fractions, 2 fractions per day, with a minimal interval of 6 hours was delivered.ResultsAt the time of the implant, the median age of patients was 59.7 years (range, 39.3-74.9 years). The median time from first treatment until BT for local recurrence was 11.9 years (range, 2.5-27.8 years). The median interval between salvage surgery and BT was 3.6 months (range, 1-8.2 months). No acute epidermitis or soft tissue side effects higher than grade 2 were recorded, with good cosmetic results in all patients. Most of the patients presented grade 1-2 late side effects. Only one patient developed grade 3 liponecrosis. After a median follow-up of 73.7 months (range, 28.8-102.4 months), the overall survival and cancer specific survival were 87.1% and 90.3%, respectively; 5-year local control and 5-year progression-free survival rate were 90.3% and 83.9%, respectively.ConclusionsOur preliminary analysis showed that HDR-BT is a feasible treatment for partial breast reirradiation offering very low complications rate and fast procedure. Higher patients’ cohort is warranted in order to define the role of this treatment modality in the breast conservative management of local recurrence.

Effectiveness of Breast-Conserving Surgery and 3-Dimensional Conformal Partial Breast Reirradiation for Recurrence of Breast Cancer in the Ipsilateral Breast

Mastectomy is standard for recurrence of breast cancer after breast conservation therapy with whole breast irradiation. The emergence of partial breast irradiation led to consideration of its application for reirradiation after a second lumpectomy for treatment of recurrence of breast cancer in the ipsilateral breast. To assess the effectiveness and adverse effects of partial breast reirradiation after a second lumpectomy and whether the treatment is an acceptable alternative to mastectomy. The NRG Oncology/Radiation Therapy Oncology Group 1014 trial is a phase 2, single-arm, prospective clinical trial of 3-dimensional, conformal, external beam partial breast reirradiation after a second lumpectomy for recurrence of breast cancer in the ipsilateral breast after previous whole breast irradiation. The study opened on June 4, 2010, and closed June 18, 2013. Median follow-up was 5.5 years. This analysis used all data received at NRG Oncology through November 18, 2018. Eligible patients experienced a recurrence of breast tumor that was less than 3 cm and unifocal in the ipsilateral breast more than 1 year after breast-conserving therapy with whole breast irradiation and who had undergone excision with negative margins. Adjuvant partial breast reirradiation, 1.5 Gy twice daily for 30 treatments during 15 days (45 Gy), using a 3-dimensional conformal technique. The main outcomes of the present study were the predefined secondary study objectives of recurrence of breast cancer in the ipsilateral breast, late adverse events (>1 year after treatment), mastectomy incidence, distant metastasis-free survival, overall survival, and circulating tumor cell incidence. A total of 65 women were enrolled, with 58 evaluable for analysis (mean [SD] age, 65.12 [9.95] years; 48 [83%] white). Of the recurrences of breast cancer in the ipsilateral breast, 23 (40%) were noninvasive and 35 (60%) were invasive. In all 58 patients, 53 (91%) had tumors 2 cm or smaller. All tumors were clinically node negative. A total of 44 patients (76%) tested positive for estrogen receptor, 33 (57%) for progesterone receptor, and 10 (17%) for ERBB2 (formerly HER2 or HER2/neu) overexpression. Four patients had breast cancer recurrence, with a 5-year cumulative incidence of 5% (95% CI, 1%-13%). Seven patients underwent ipsilateral mastectomies for a 5-year cumulative incidence of 10% (95% CI, 4%-20%). Both distant metastasis-free survival and overall survival rates were 95% (95% CI, 85%-98%). Four patients (7%) had grade 3 and none had grade 4 or higher late treatment adverse events. For patients experiencing recurrence of breast cancer in the ipsilateral breast after lumpectomy and whole breast irradiation, a second breast conservation was achievable in 90%, with a low risk of re-recurrence of cancer in the ipsilateral breast using adjuvant partial breast reirradiation. This finding suggests that this treatment approach is an effective alternative to mastectomy.

Partial-Breast Reirradiation with Intraoperative Radiotherapy (IORT) for Patients Affected By Breast Cancer after Prior Thoracic Radiotherapy

Mastectomy is currently recommended for patients suffering of new or recurrent breast cancer after prior thoracic radiation. The normal tissue tolerance does not permit a second full-dose course of whole breast irradiation after a second breast-conserving surgery (BCS). We retrospectively investigated the role of a second BCS followed by intraoperative radiotherapy (IORT) for patients with localized breast cancer and prior thoracic radiation. Twenty-five patients, who declined salvage mastectomy for their breast cancer after prior thoracic radiation, were treated with BCS and IORT between 2009 and 2018. Twenty patients (74%) presented breast cancer local relapse after whole breast irradiation, seven (26%) previously received mantle field irradiation for Hodgkin Lymphoma. All breast tumors/recurrences were T1 and unifocal. IORT was delivered with the low energy X-rays IntrabeamTM device (Carl Zeiss Meditec AG, Oberkochen, Germany), using a single dose of 6 Gy prescribed to a depth of 1 cm from applicator surface (20-21Gy at applicator surface). Local control (LC), mastectomy free survival (MFS), disease free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier estimator. Treatment-related toxicities were scored by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The median time from prior thoracic radiation to breast cancer presentation was 14 years (range 6-34). All patients successfully underwent BCS and partial breast reirradiation with IORT without acute toxicity. The median follow-up from IORT was 61 months (range 2-117 months). Two patients with local recurrence underwent salvage mastectomy; among whom one had a second local relapse and started chemotherapy. One patient deceased from brain metastases. No other local or distant relapses were detected. LC, MFS, DFS, and OS at five years were 94%, 92.3%, 88.2% and 94% respectively. No cases of late Grade ≥3 toxicity were registered. In our retrospective experience, BCS with IORT is a feasible option for breast preservation in patients with localized breast cancer / recurrence and prior thoracic radiation. Treatment tolerance was excellent. Prospective trials are required to confirm these preliminary findings.

2ndconservative Treatment for 2ndipsilateral Breast Tumor Event: Mature Oncological Results and Prognostic Factors from the GEC-Estro Bcwg.

In case of second ipsilateral breast tumor event (2ndIBTE) occurring after primary radio-surgical treatment, salvage mastectomy or 2ndconservative treatment (2ndCT) including an accelerated partial breast re-irradiation (APBrI) can be discussed according to patient and tumor features. We report updated results from the database of the GEC-ESTRO Breast Cancer Working Group. Between 2000 and 2014, 343 patients (pts) underwent a 2ndCT in 12 hospital/cancer centers from 7 European countries. After lumpectomy, APBrI was performed using either low (30 – 55 Gy reference isodose) or high dose-rate brachytherapy (28 - 34 Gy). Oncological outcome including 3rdIBTE-free survival and overall survival (OS) was analyzed. Univariate (UVA) and multivariate analyses (MVA) were conducted to identify significant prognostic factors for 3rdIBTE including the belonging to one of the 3 sub-groups of the GEC-ESTRO APBI classification (GAC) and the tumor molecular profile (MP - JAMA. 2019;321:288-300). Late toxicity was reported. With a median follow-up of 72 months (range: 64 - 80 months), 150 pts (44%), 144 pts (42 %) and 49 pts (14%) were classified as low (LR), intermediate (IR) and high-risk (HR) respectively. Regarding the molecular profile (excluding in situ carcinomas), 233 pts (77%), 28 pts (10%) and 40 pts (13%) were positive hormonal receptors (HR+), over-expressed Her2 (Her2+) and triple negative (TN) respectively. For the whole cohort, 6-year 3rdIBTE-free survival and OS rates were 94.6% and 85.9% respectively. For the cohort excluding in situ carcinomas, 6-year 3rdIBTE-free survival and OS rates were 93.8% and 84.8% respectively. In UVA, SBR (1,2 vs 3 - p = 0.008), age (< 50 y vs. 50 y - p = 0.001), GAC (p = 0.001) and MP (p = 0.05) were considered as significant prognostic factors for 3rdIBTE, while, in MVA, SBR (HR 3.3 CI: 1.269 - 8.585; p = 0.01) and GAC (HR 8.4 CI: 1.878 - 37.864; p = 0.004) were the two remaining prognostic factors. In terms of late toxicity, 194 pts (87%) presented G1,2 complications while G>=3 complication rate was 13%. In case of 2ndIBTE, 2ndCT combining re-lumpectomy + APBrI represent a valid therapeutic option in terms of oncological outcome as well as toxicity profile. Patient and tumor characteristics have to be carefully evaluated while patient information remains crucial for the discussion of treatment choice.

GEC-ESTRO APBI classification as a decision-making tool for the management of 2nd ipsilateral breast tumor event.

Second ipsilateral breast tumor event (2ndIBTE) occurring after primary radio-surgical treatment can be treated by either salvage mastectomy or 2nd conservative treatment (2ndCT) including an accelerated partial breast re-irradiation (APBrI). We analyzed the impact of the GEC-ESTRO APBI classification (GAC) on the oncological outcome after APBrI. Between 2000 and 2016, 159 patients (pts) underwent a 2ndCT. After lumpectomy, APBrI was performed using either low-dose (30-55Gy reference isodose) or high-dose rate brachytherapy (28-34Gy). Oncological outcome including 3rdIBTE, regional (RFS) or metastasis-free survival (MFS), specific (SS) and overall survival (OS) was analyzed according to GAC. Univariate (UVA) and multivariate analyses (MVA) were conducted to identify significant prognostic factors for 3rdIBTE. With a median follow-up of 71months (range 62-85months), 60 pts (42%), 61 pts (42.7%) and 22 pts (15.4%) were classified as low-risk (LR), intermediate-risk (IR) and high-risk (HR), respectively. For the whole cohort, 6-year 3rdIBTE-free survival, RFS, MFS, SS and OS rates were 97.4, 96.4, 90.3, 92.9 and 91.2%, respectively. Six-year 3rdIBTE-free survival rates for LR, IR and HR were 100, 95.8 and 92.9%, respectively (p = 0.003), while no significant differences were found between the three GAC groups for RFS, MFS, SS. In UVA, lympho-vascular invasion (p = 0.009), positive margins (p = 0.0001) and GAC high-risk group (p = 0.001) were considered as significant prognostic factors for 3rdIBTE, while, in MVA, high-risk group (p = 0.009) was the only prognostic factor. In case of 2ndIBTE, GAC could be used as a decision helping tool to discuss conservative or radical treatment options. Patient information remains crucial in order to accurately define the salvage therapy modalities.

Second breast conserving therapy after ipsilateral breast tumor recurrence – a 10-year experience of re-irradiation

PurposeThe aim of this study is to evaluate the efficacy and toxicity of post-operative partial breast re-irradiation with multi-catheter brachytherapy after second breast conserving therapy (BCT) in patients with small, low-risk ipsilateral breast tumor recurrence (IBTR).Material and methodsBetween 2008 and 2018, 19 consecutive patients with low-risk IBTR (max. rpT1 cN0 cM0, Her2 negative, preferably positive hormone receptor status) who refused mastectomy were treated with salvage lumpectomy, followed by post-operative partial breast re-irradiation with multi-catheter brachytherapy. Eight patients were irradiated using PDR brachytherapy (49.8-50.4 Gy in pulses of 0.5-0.7 Gy) and 11 patients using HDR brachytherapy (34.2 Gy in fractions of 3.8 Gy or 32 Gy in fractions of 4 Gy). All patients had undergone prior BCT for their primary tumor, followed by adjuvant whole breast radiotherapy. Local control (LC), locoregional control (LRC), overall survival (OS), disease-free survival (DFS) as well as toxicity were evaluated in the present study.ResultsAfter a median follow-up of 65 months following IBTR (18-120 months), only one second IBTR in 19 patients was diagnosed 77 months after re-irradiation, resulting in a LC rate of 100% at 5 years. DFS and OS rates were both 100% at 5 years following re-irradiation. Except for the above mentioned second IBTR, no regional or distant relapse was recorded. Regarding toxicity, 63% of patients developed adverse events (CTCAE grade ≤ 2), with fibrosis detected in 37% (7/19) of patients, necrosis in 11% (2/19), hyperpigmentation in 47% (9/19), and telangiectasia in 11% (2/19), respectively. No patient showed a high-grade (CTCAE grade ≥ 3) adverse event.ConclusionsIn case of small, low-risk IBTR, adjuvant re-irradiation using multi-catheter brachytherapy is a feasible, safe, and effective treatment method after repeated lumpectomy, and an alternative to mastectomy.

NRG Oncology/RTOG 1014: Patient Reported Outcomes (PRO) and Cosmesis From a Phase II Study of Repeat Breast Preserving Surgery and 3D Conformal (3D-CRT) Partial Breast Re-Irradiation (PBrI) for In-Breast Recurrence.

NRG/RTOG 1014 is a prospective phase II trial of 3D-CRT PBrI following repeat lumpectomy for in-breast recurrence following previous whole breast irradiation (WBI). This analysis focuses on patient reported and cosmetic outcomes. Eligible patients (pts) had in-breast recurrences presenting >1 year following WBI for initial lesion, were confirmed to be <3cm, unifocal and resected with negative margins. Prescription dose of 45 Gy was delivered as 1.5Gy BID for 30 treatments with 3D-CRT. PRO were collected using the Breast Cancer Treatment Outcome Scale (BCTOS) where change compared to the contralateral breast is graded as 1 = none, 2 = slight, 3 = moderate and 4 = large and analyzed in three domains: functional (e.g. shoulder or arm movement, stiffness, pain) , cosmetic (e.g. breast size, texture, shape, scar tissue ) and breast-specific pain (e.g. breast pain, tenderness, sensitivity). MD assessment was done using a four point NRG/RTOG established criteria scale. The BCTOS and MD Cosmetic Score were completed at baseline (prior to the start of PBrI, but after surgery), 12 months (mo), and 36 mo intervals. Of the 58 pts eligible and treated, 46 (79%) consented to the Quality of Life component. BCTOS mean + standard deviation (SD) at baseline, 12 and 36 mo in the table demonstrate that functional status was unchanged over the observation period, breast-specific pain improved and cosmesis worsened slightly at 12 mo and 36 mo.Abstract 84; TableBCTOS Mean + SDFunctionalCosmeticBreast-Specific PainBaseline (n=46)1.27 ± 0.421.95 ± 0.551.92 ± 0.5412-month (n=36)1.28 ± 0.432.05 ± 0.661.70 ± 0.6436-month (n=32)1.29 ± 0.472.12 ± 0.711.76 ± 0.83 Open table in a new tab MD-assessed fibrosis, volume loss, retraction and/or pigment change was scored as effecting cosmesis at baseline (n=44) in 9%, 41%, 28%, 7%, respectively; worsening to 21%, 49%, 36%, 8% at 12 mo (n=39); and, 43%, 57%, 53%, 7% at 36 mo (n=30), respectively. MD assessed cosmesis was excellent/good in 59%, 63% and 52% respectively and Fair/Poor 41%, 37% and 48% respectively at baseline (n=44), 12 mo (n=35) and 36 mo (n=27). When evaluating individual pts with all time points available, improvements and deteriorations in MD scoring were seen. BCTOS cosmetic status mean score correlated to the MD- assessed four point score at the 12 mo interval: BCTOS mean score of 1.67 ± 0.57, 1.88 ± 0.44, 2.19 ± 0.69, and 2.48 ± 1.21 corresponding to the MD assessment of excellent, good, fair, and poor, respectively. Based on PRO, repeat lumpectomy with PBrI had no impact on functional status, breast-specific pain improved over time, and there was a small worsening of cosmesis. MD assessment of cosmesis correlated with this trend. Fibrosis, volume loss, retraction, pigment change were the MD identified factors most commonly affecting cosmesis at 12 and 36 months.

ESTRO-ACROP guideline: Interstitial multi-catheter breast brachytherapy as Accelerated Partial Breast Irradiation alone or as boost – GEC-ESTRO Breast Cancer Working Group practical recommendations

PurposeThis consensus statement from the Breast Cancer Working Group of Groupe Européen de Curiethérapie of European Society for Radiotherapy and Oncology (GEC-ESTRO) aims at generating practical guidelines for multi-catheter image-guided brachytherapy in the conservative management of breast cancer patients used for either Accelerated Partial Breast Irradiation (APBI) or for a breast boost. MethodsRecent advances in techniques of multi-catheter brachytherapy were summarized and all the relevant literature was reviewed by a panel of experts. Panel members of the GEC-ESTRO experts participated in a series of conferences, supplemented their clinical experience, were surveyed to determine their current practices and patterns, performed a literature review, and formulated recommendations for implementing APBI with multi-catheter brachytherapy, focusing on treatment planning issues, catheter insertion, dosimetry and quality assurance. This document was reviewed and approved by the full panel, the GEC-ESTRO executive board and by the ACROP (Advisory Committee on Radiation Oncology Practice). ResultsThree-dimensional (3D) treatment planning, catheter insertion techniques, dosimetry and methods of quality assurance for APBI and boost with multi-catheter image-guided brachytherapy after breast conserving surgery are described. Detailed recommendations for daily practice including dose constraints are given. ConclusionsRecent standards and guidelines for the use of APBI with different multi-catheter image-guided brachytherapy techniques have been defined. Different techniques are used to insert the catheters. Guidelines are mandatory to assure precise catheter insertion for coverage of the target volume and to guarantee high-quality dosimetry. The same rules apply for brachytherapy based boost irradiation for breast cancer after whole breast irradiation as well as for partial breast re-irradiation.