De-escalation of radiotherapy after primary chemotherapy in cT1-2N1 breast cancer (RAPCHEM; BOOG 2010-03): 5-year follow-up results of a Dutch, prospective, registry study.

Background: Primary chemotherapy in breast cancer poses a dilemma with regard to adjuvant locoregional radiotherapy, as guidelines for locoregional radiotherapy were originally based on pathology results of primary surgery. We aimed to evaluate the oncological safety of de-escalated locoregional radiotherapy in patients with cT1-2N1 breast cancer treated with primary chemotherapy, according to a predefined, consensus-based study guideline.

Methods: In this prospective registry study (RAPCHEM, BOOG 2010-03), patients referred to one of 17 participating radiation oncology centres in the Netherlands between Jan 1, 2011, and Jan 1, 2015, with cT1-2N1 breast cancer (one to three suspicious nodes on imaging before primary chemotherapy, of which at least one had been pathologically confirmed), and who were treated with primary chemotherapy and surgery of the breast and axilla were included in the study.

Three-year follow-up of de-escalated axillary treatment after neoadjuvant systemic therapy in clinically node-positive breast cancer: the MARI-protocol.

Purpose: In clinically node-positive (cN+) breast cancer patients, evidence supporting response-guided treatment after neoadjuvant systemic therapy (NST) instead of axillary lymph node dissection (ALND) is increasing, but follow-up results are lacking. We assessed three-year axillary recurrence-free interval (aRFI) in cN+ patients with response-adjusted axillary treatment according to the 'Marking Axillary lymph nodes with Radioactive Iodine seeds' (MARI)-protocol.

Methods: We retrospectively assessed all stage II-III cytologically proven cN+ breast cancer patients who underwent the MARI-protocol between July 2014 and November 2018.

[Partial breast irradiation].

Breast-conserving therapy (BCT), consisting of local excision of the tumor followed by whole breast radiotherapy, is nowadays considered standard of care for early stage breast cancer. For patients at low risk of local recurrence, partial breast irradiation (PBI) is an alternative treatment. The rationale for PBI is that irradiation of only the tumour bed and surrounding area will result in less toxicity, while maintaining an acceptable low local recurrence rate as most of the local recurrences occur at or near the original tumor site.

Long-term risk of subsequent ipsilateral lesions after surgery with or without radiotherapy for ductal carcinoma in situ of the breast.

Background: Radiotherapy (RT) following breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) reduces ipsilateral breast event rates in clinical trials. This study assessed the impact of DCIS treatment on a 20-year risk of ipsilateral DCIS (iDCIS) and ipsilateral invasive breast cancer (iIBC) in a population-based cohort.

Methods: The cohort comprised all women diagnosed with DCIS in the Netherlands during 1989-2004 with follow-up until 2017.

Unexpected toxicity of CDK4/6 inhibitor palbociclib and radiotherapy.

Background: Cyclin-dependent kinase (CDK) 4/6 inhibitors have recently been approved for the treatment of hormone receptor-positive and HER2-negative metastatic breast cancer in association with endocrine therapy in postmenopausal women. Data on the interaction of CDK4/6 inhibition and radiotherapy are scarce, but some studies show unexpected toxicity.

Cases: We report three cases of unexpected severe or prolonged soft tissue, skin, and gastrointestinal toxicity in patients treated with a combination of radiotherapy and the CDK4/6 inhibitor palbociclib.

Evaluation of Early Response to Preoperative Accelerated Partial Breast Irradiation (PAPBI) by Histopathology, Magnetic Resonance Imaging, and 18F-fluorodexoyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT).

Purpose: This study aimed to find indicators for early response to radiation therapy in breast cancer. These would be of help in tailoring treatment for individual patients.

Methods And Materials: We analyzed 66 patients with low-risk breast cancer (≥60 years; cT1-2pN0) treated within the Preoperative Accelerated Partial Breast Irradiation (PAPBI) trial.

A case-control study to identify molecular risk factors for local recurrence in young breast cancer patients.

Purpose: To investigate risk factors for local recurrence (LR) after breast conserving therapy in young breast cancer patients randomized in the "Young Boost Trial".

Material & Methods: In the "Young Boost Trial" 2421 patients ≤50 years old were randomized between a 16 Gy and 26 Gy boost after breast conserving surgery and whole breast radiation (50 Gy). We performed a case-control study comparing patients who developed a LR (cases) and for each of them three control patients free of recurrence (controls).

Radiotherapy after primary CHEMotherapy (RAPCHEM): Practice variation in a Dutch registration study (BOOG 2010-03).

Background: We conducted a prospective cohort study in the Netherlands (RAPCHEM: NCT01279304, BOOG 2010-03) in breast cancer (BC) patients treated with primary systemic therapy (PST), followed by surgery and post-operative radiation therapy (RT) according to a predefined consensus-based study-guideline (SG). The aim of the current analysis is to evaluate adherence to the SG.

Methods: From January 2011 to January 2015, patients with cT1-2N1 BC treated in 17 Dutch RT Centres were included.

Five-Year Results of the Preoperative Accelerated Partial Breast Irradiation (PAPBI) Trial.

Purpose: In this multicenter phase 2 feasibility study, we investigated the impact of preoperative accelerated partial breast irradiation (PAPBI) on local control, breast fibrosis, and cosmetic outcome.

Methods And Materials: Women aged >60 years with an invasive, unifocal (mammography and magnetic resonance imaging), nonlobular adenocarcinoma of the breast were treated with PAPBI. Six weeks after radiation therapy, a wide local excision was performed.

Response to Preoperative Radiation Therapy in Relation to Gene Expression Patterns in Breast Cancer Patients.

Purpose: We aimed to study radiation-induced gene expression changes and to identify differences in gene expression between patients with and without response to radiation therapy (RT) for invasive breast cancer with the purpose of exploring whether a predictive signature could be developed. Such a signature could assist in optimizing individualized locoregional treatment.

Methods And Materials: RNA-seq using next-generation sequencing was performed on fresh frozen samples from pretreatment biopsies and post-RT surgery specimens from patients with low-risk breast cancer treated within the multicenter preoperative accelerated partial breast irradiation trial.

Predictive risk factors for sentinel lymph node nonvisualization on planar lymphoscintigraphy using an intratumoral injection in patients with primary breast cancer.

Objectives: Lymphoscintigraphy is considered a useful tool to optimize sentinel lymph node (SLN) identification. Nonvisualization of the SLN is associated with a lower SLN identification rate. The aim of this study was to identify preoperative factors associated with SLN nonvisualization on lymphoscintigraphy.

Internal Mammary Chain Sentinel Nodes in Early-Stage Breast Cancer Patients: Toward Selective Removal.

Background: Removal of internal mammary chain sentinel nodes (IMCSNs) affects prognosis and treatment of breast cancer, and internal mammary chain radiotherapy (IMCRT) can improve survival for selected patients. This study aimed to determine the effect of IMCSN biopsy on recurrence-free survival (RFS) and overall survival (OS) and to identify predictive factors for IMCSN and distant metastasis.

Methods: Patients with IMCSNs were selected from a prospective database for the period 1999-2007.

Breast-shape changes during radiation therapy after breast-conserving surgery.

Background & Purpose: With the introduction of more conformal techniques for breast cancer radiation therapy (RT), motion management is becoming increasingly important. We studied the breast-shape variability during RT after breast-conserving surgery (BCS).

Materials & Methods: Planning computed tomography (CT) and follow-up cone-beam CT (CBCT) scans were available for 71 fractions of 17 patients undergoing RT after BCS.

Prognostic Factors for Local Control in Breast Cancer After Long-term Follow-up in the EORTC Boost vs No Boost Trial: A Randomized Clinical Trial.

Importance: Prognostic factors of ipsilateral breast tumor recurrence (IBTR) may change over time following breast-conserving therapy.

Objective: The EORTC "boost no boost" trial showed that young age and high-grade invasive carcinoma were the most important risk factors for IBTR. This study reanalyses pathological prognostic factors related to IBTR using long-term follow-up.

Low risk of recurrence in elderly patients treated with breast conserving therapy in a single institute.

Objectives: To guide decision making in preventing over- or under-treatment in older breast cancer patients who have undergone breast conserving surgery, we analyzed prognostic factors and risk of recurrence in a consecutive series of patients ≥ 65 years old with breast cancer and identified subgroups that may benefit or not from more intensive treatment.

Methods: Patients ≥65 years of age with breast cancer (pT1-2/pN0-2) treated with breast conserving surgery and postoperative radiation therapy at the Netherlands Cancer Institute (NKI) between 1980 and 2008 were identified. Endpoints were locoregional recurrence (LRR), distant metastasis (DM) and overall survival (OS).

First results of the preoperative accelerated partial breast irradiation (PAPBI) trial.

Background And Purpose: The aim of this study is to assess the toxicity and cosmetic outcome of preoperative accelerated partial breast irradiation (PAPBI) for breast cancer patients with low risk on local recurrence.

Material And Methods: Women aged ⩾60years with an invasive, unifocal ⩽3cm on MRI, (non-lobular) adenocarcinoma of the breast and a negative sentinel node received PAPBI (40Gray in 10 fractions over 2 weeks). Six weeks after radiotherapy a wide local excision was performed.

Target volume delineation in external beam partial breast irradiation: less inter-observer variation with preoperative- compared to postoperative delineation.

The challenge of adequate target volume definition in external beam partial breast irradiation (PBI) could be overcome with preoperative irradiation, due to less inter-observer variation. We compared the target volume delineation for external beam PBI on preoperative versus postoperative CT scans of twenty-four breast cancer patients.

Estimation of heart-position variability in 3D-surface-image-guided deep-inspiration breath-hold radiation therapy for left-sided breast cancer.

Purpose: To investigate the heart position variability in deep-inspiration breath-hold (DIBH) radiation therapy (RT) for breast cancer when 3D surface imaging would be used for monitoring the BH depth during treatment delivery. For this purpose, surface setup data were compared with heart setup data.

Materials And Methods: Twenty patients treated with DIBH-RT after breast-conserving surgery were included.

Pre-chemotherapy 18F-FDG PET/CT upstages nodal stage in stage II-III breast cancer patients treated with neoadjuvant chemotherapy.

In breast cancer patients treated with neoadjuvant chemotherapy (NAC) the number of tumor-positive nodes can no longer reliably be determined. Furthermore, ultrasound (US) seems suboptimal for the detection of N3-disease. Therefore we assessed the proportion of breast cancer patients treated with NAC in which pre-chemotherapy 18F-FDG PET/CT detected ≥4 axillary nodes or occult N3-disease, upstaging nodal status and changing risk estimation for locoregional recurrence (LRR).

Tumor bed delineation for external beam accelerated partial breast irradiation: a systematic review.

In recent years, accelerated partial breast irradiation (APBI) has been considered an alternative to whole breast irradiation for patients undergoing breast-conserving therapy. APBI delivers higher doses of radiation in fewer fractions to the post-lumpectomy tumor bed with a 1-2 cm margin, targeting the area at the highest risk of local recurrence while sparing normal breast tissue. However, there are inherent challenges in defining accurate target volumes for APBI.

Accuracy of 18F-FDG PET/CT for primary tumor visualization and staging in T1 breast cancer.

Background: The aim of this study was to assess the accuracy of 18F-FDG PET/CT in T1 breast cancer regarding visualization of the primary tumor and the detection of locoregional and distant metastases.

Methods: Sixty-two women with invasive T1 breast cancer underwent a PET/CT. Image acquisition of the thorax was done in prone position with hanging breasts, followed by whole-body scanning in supine position.

Locoregional lymph node involvement on 18F-FDG PET/CT in breast cancer patients scheduled for neoadjuvant chemotherapy.

The optimal method for locoregional staging in patients treated with neoadjuvant chemotherapy (NAC), usually ultrasound (US) and pre- or post-chemotherapy sentinel lymph node biopsy (SLNB), remains subject of debate. The aim of this study was to assess the value of 18F-FDG PET/CT for detecting locoregional lymph node metastases in primary breast cancer patients scheduled for NAC. 311 breast cancer patients, scheduled for NAC, underwent PET/CT of the thorax in prone position with hanging breasts.