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. The study guideline comprised three risk groups for locoregional recurrence, with corresponding locoregional radiotherapy recommendations: no chest wall radiotherapy and no regional radiotherapy in the low-risk group, only local radiotherapy in the intermediate-risk group, and locoregional radiotherapy in the high-risk group. Radiotherapy consisted of a biologically equivalent dose of 25 fractions of 2 Gy, with or without a boost. During the study period, the generally applied radiotherapy technique in the Netherlands was forward-planned or inverse-planned intensity modulated radiotherapy. 5-year follow-up was assessed, taking into account adherence to the study guideline, with locoregional recurrence rate as primary endpoint. We hypothesised that 5-year locoregional recurrence rate would be less than 4% (upper-limit 95% CI 7·8%). This study was registered at ClinicalTrials.gov, NCT01279304, and is completed. FINDINGS: 838 patients were eligible for 5-year follow-up analyses: 291 in the low-risk group, 370 in the intermediate-risk group, and 177 in the high-risk group. The 5-year locoregional recurrence rate in all patients was 2·2% (95% CI 1·4-3·4). The 5-year locoregional recurrence rate was 2·1% (0·9-4·3) in the low-risk group, 2·2% (1·0-4·1) in the intermediate-risk group, and 2·3% (0·8-5·5) in the high-risk group. If the study guideline was followed, the locoregional recurrence rate was 2·3% (0·8-5·3) for the low-risk group, 1·0% (0·2-3·4) for the intermediate-risk group, and 1·4% (0·3-4·5) for the high-risk group. INTERPRETATION: In this study, the 5-year locoregional recurrence rate was less than 4%, which supports our hypothesis that it is oncologically safe to de-escalate locoregional radiotherapy based on locoregional recurrence risk, in selected patients with cT1-2N1 breast cancer treated with primary chemotherapy, according to this predefined, consensus-based study guideline. FUNDING: Dutch Cancer Society. TRANSLATION: For the Dutch translation of the abstract see Supplementary Materials section.

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. Pre-NST axillary staging with FDG-PET/CT (less- or more than four suspicious axillary nodes; cALN < 4 or cALN ≥ 4) and post-NST pathological axillary response measured in the pre-NST largest tumor-positive axillary lymph node marked with an iodine seed (MARI-node; ypMARI-neg or ypMARI-pos) determined axillary treatment: no further treatment (cALN < 4, ypMARI-neg), axillary radiotherapy (ART) (cALN < 4, ypMARI-pos and cALN ≥ 4, ypMARI-neg) or ALND plus ART (cALN ≥ 4, ypMARI-pos). RESULTS: Of 272 women included, the MARI-node was tumor-negative in 56 (32%) of 174 cALN < 4 patients and 43 (44%) of 98 cALN ≥ 4 patients. According to protocol, 56 (21%) patients received no further axillary treatment, 161 (59%) received ART and 55 (20%) received ALND plus ART. Median follow-up was 3.0 years (IQR 1.9-4.1). Five patients (one no further treatment, four ART) had axillary metastases. Three-year aRFI was 98% (95% CI 96-100). The overall recurrence risk remained highest for patients with ALND (HR 4.36; 95% CI 0.95-20.04, p = 0.059). CONCLUSIONS: De-escalation of axillary treatment according to the MARI-protocol prevented ALND in 80% of cN+ patients with an excellent three-year aRFI of 98%.

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. CONCLUSION: These cases indicate a possible interaction between radiotherapy and palbociclib. Therefore, we recommend using radiotherapy cautiously when combined with CDK4/6 inhibitors.

[Partial breast irradiation]. / Partiële borstbestraling.

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. Because the target volume is smaller than with WBI, reduced toxicity is expected and a higher dose per fraction can be applied. As a result, overall treatment time can be reduced. There are various methods to deliver PBI, including brachytherapy, intraoperative radiation therapy, and external beam radiation therapy (EBRT). Multiple studies showed less toxicity and similar or improved cosmetic outcome after PBI using EBRT.

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. Cumulative incidence of iDCIS and iIBC following BCS and BCS + RT were assessed. Associations of DCIS treatment with iDCIS and iIBC risk were estimated in multivariable Cox models. RESULTS: The 20-year cumulative incidence of any ipsilateral breast event was 30.6% (95% confidence interval (CI): 28.9-32.6) after BCS compared to 18.2% (95% CI 16.3-20.3) following BCS + RT. Women treated with BCS compared to BCS + RT had higher risk of developing iDCIS and iIBC within 5 years after DCIS diagnosis (for iDCIS: hazard ratio (HR)age < 50 3.2 (95% CI 1.6-6.6); HRage ≥ 50 3.6 (95% CI 2.6-4.8) and for iIBC: HRage<50 2.1 (95% CI 1.4-3.2); HRage ≥ 50 4.3 (95% CI 3.0-6.0)). After 10 years, the risk of iDCIS and iIBC no longer differed for BCS versus BCS + RT (for iDCIS: HRage < 50 0.7 (95% CI 0.3-1.5); HRage ≥ 50 0.7 (95% CI 0.4-1.3) and for iIBC: HRage < 50 0.6 (95% CI 0.4-0.9); HRage ≥ 50 1.2 (95% CI 0.9-1.6)). CONCLUSION: RT is associated with lower iDCIS and iIBC risk up to 10 years after BCS, but this effect wanes thereafter.

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. Patients received radiation therapy (RT; 10 x 4 Gray or 5 x 6 Gray), followed by a wide local excision after 6 weeks. Patients underwent magnetic resonance imaging (MRI) and 18F-fluorodexoyglucose (FDG) positron emission tomography/computed tomography (PET/CT) before RT and 5 weeks after RT, before surgery. We assessed the response to PAPBI using a histopathologic assessment and correlated this with responses on MRI and FDG PET/CT. We calculated the positive predictive values (PPVs) of MRI and PET/CT as the number of true positives (complete response on MRI/normalized at visual evaluation on PET/CT and pathologic complete response) divided by the number of patients with a complete response on MRI/normalized at visual evaluation on PET/CT. Similarly, the negative predictive values (NPVs) of MRI and PET/CT were calculated. RESULTS: The pathologic response was (nearly) complete in 15 (23%) of the 66 patients and partially complete in 28 (42%). The remaining 23 patients (35%) were nonresponders. The PPV of MRI (Response evaluation criteria in solid tumors [RECIST]) was 87.5% and the NPV was 85%. The PPV and NPV of PET/CT were 25% and 92%, respectively. CONCLUSIONS: The most accurate method to predict a response and residual disease after preoperative RT in low-risk breast cancer was MRI, using RECIST.

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). Clinicopathological factors, copy number- and gene expression profiles of primary tumors were compared between cases and controls, and between primary tumors and local recurrences. RESULTS: The cumulative 5-year LR rate was 1.07% (95% CI 0.72-1.59%) and 10-year LR rate 2.56% (1.81-3.62%). Analysis of a subset of primary tumors and local recurrences showed similar histopathological characteristics (n = 15), copy number (n = 13) and gene expression profiles (n = 14). Basal subtype was strongly associated with LR in univariable and multivariable analysis. Gains of CCND1 were identified more frequently among controls, while more frequent gains of FGFR1 and IGF1R were observed among cases. Upregulation of genes involved in the p53-pathway was observed in recurring tumors compared to non-recurring tumors. We could not identify a genomic classifier for LR. CONCLUSIONS: All investigated local recurrences were true genomic recurrences. Although differences in copy number variation and gene expression pathways were observed in recurring tumors compared to non-recurring tumors, no genomic classifier for LR could be identified.

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. Patients with four or more suspicious nodes at imaging were excluded. SG recommended whole breast RT for patients treated with breast conserving therapy. SG on loco(-regional) RT were defined for three risk groups based on the ypN status: (1) ypN0 (low-risk): RT breast and no RT after mastectomy; (2) ypN1 (intermediate-risk): RT breast or chest wall; (3) ypN2 (high-risk): RT breast or chest wall, including regional lymph nodes. RESULTS: We included 848 patients: 292 in the low-risk group; 374 in the intermediate-risk group; 182 in the high-risk group. Overall, 64% of the patients was treated according to the SG; 11% received less RT than the predefined target volumes and 25% received more extensive RT than according to the SG. The largest variation was seen in the intermediate risk group, where only 54% was treated according to the SG. CONCLUSION: Substantial deviation from the SG for post-operative RT was observed after PST, especially in patients with an intermediate-risk. Future analyses will evaluate outcome of these patients in relation to risk factors and the actual RT given.

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. Radiation therapy consisted of 10 × 4 Gy (2010-2013) or 5 × 6 Gy (after 2013) to the tumor (gross target volume) with a 25 mm margin (20 mm from gross target volume to clinical target volume, 5 mm planning target volume). RESULTS: One hundred thirty-three patients treated between 2010 and 2016 were analyzed with a median follow-up of 5.0 years (0.9-8.8 years). Seventy-eight (59%) patients were treated with 10 × 4 Gy in 2 weeks and 55 (41%) patients with 5 × 6 Gy in 1 week. Eighteen postoperative complications (14%) occurred in 15 patients (11%). The proportion of patients with no to mild fibrosis in the treated part of the breast at 2 years and later time points was around 90%. Cosmesis improved over time in several patients: excellent to good cosmetic score as rated by the physician was 68% at 6 months and 92% at 5 years. Seventy-seven percent (6 months) to 82% (5 years) of patients were "satisfied" or "very satisfied" with their cosmetic outcome. Three recurrences were detected in the biopsy track and 1 recurrence in the ipsilateral breast. CONCLUSIONS: PAPBI is a feasible method with a low postoperative complication rate, limited fibrosis, and good to excellent cosmetic outcome. The local recurrence rate was 3% at 5 years; however, no local recurrences were observed since removal of the needle biopsy track.

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. Patients were treated with preoperative RT (10 × 4 Gy in 10 days or 5 × 6 Gy in 5 days) and a lumpectomy 6 weeks thereafter. The response of the tumor to RT was evaluated by pathologic assessment. To analyze the gene expression data, unsupervised and supervised clustering was performed. Gene expression profiles were compared between biopsies of responders and nonresponders and between samples before and after RT. RESULTS: Ninety-four samples from 77 patients were analyzed: 68 pretreatment biopsies and 26 post-RT surgery specimens. Six patients had a (near) complete pathologic response, 3 patients had a good response, 32 patients had a partial response, and 22 patients had no or very limited response. Comparing patients with and without response to RT, 25 genes were significantly differentially expressed and were not linked to a pathway. Comparison of samples before and after RT identified significant changes in gene expression. Genes involved in p53 signaling, TNFA1 signaling, apoptosis, epithelial mesenchymal transition, and inflammatory response were upregulated. Genes involved in mitotic spindle, G2M checkpoint, and E2F targets were downregulated. CONCLUSIONS: Radiation-induced gene expression changes mainly involved p53 signaling, cell cycle regulation, DNA repair, and inflammatory response. No clinically significant differences could be identified in gene expression between patients with and without response to RT.

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. PATIENTS AND METHODS: A total of 2050 consecutive SLN procedures were evaluated from clinically node-negative breast cancer patients. Planar lymphoscintigraphy was performed at 3 h after an intratumoral injection of technetium-99m-nanocolloid. This technique was used for extra-axillary SLN identification. Patient, tumor, and treatment characteristics were analyzed for association with SLN nonvisualization. Factors with a P-value less than 0.1 in univariate analysis were included in a multivariate logistic regression model. RESULTS: The SLN visualization rate was 86.7%. In multivariate logistic regression, age of at least 70 years [odds ratio (OR): 3.24; 95% confidence interval (CI): 2.14-4.91)], BMI of at least 30 (OR: 1.93; 95% CI: 1.39-2.69), T3/T4-tumors (OR: 2.70; 95% CI: 1.37-5.32), medially/centrally located tumors (OR: 1.52; 95% CI: 1.17-1.99), previous mantle field radiation (OR: 4.04; 95% CI: 1.74-9.35), nonpalpable tumors (OR: 1.88; 95% CI: 1.36-2.60), and presence of iodine seeds (OR: 1.35; 95% CI: 1.02-1.78) were associated significantly with nonvisualization on lymphoscintigraphy. Nonvisualization was the strongest independent predictor of unsuccessful intraoperative SLN identification (P<0.001). Overall, the SLN identification rate was 97.7% because of the use of additional imaging and blue dye. CONCLUSION: This study reports new tumor and treatment-related risk factors for nonvisualization on lymphoscintigraphy by using an intratumoral injection in primary breast cancer. We recommend a periareolar subcutaneous injection to improve SLN visualization in patients with limited prognostic and therapeutic relevance of internal mammary chain SLN identification.

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. Lymphoscintigraphy was performed after intratumoral technetium-99 m injection, and all sentinel nodes were removed. Both RFS and OS were calculated for subgroups with tumor-positive, tumor-negative, or non-removed IMCSNs. Predictive factors were identified for tumor-positive IMCSNs and distant metastasis by regression analysis. RESULTS: For 287 (85%) of 336 patients, IMCSN biopsy was performed, and metastasis was detected in 38 patients (13%). The patients with tumor-positive IMCSNs had poorer OS than the patients with no IMCSN metastasis or non-removed IMCSNs (p = 0.002). These patients also had worse RFS due to distant metastasis (p = 0.002). Axillary metastasis was predictive for tumor-positive IMCSNs (positive predictive value, 38.5%). The predictive factors for distant metastasis were tumor-positive IMCSNs (hazard ratio [HR], 2.5), non-removed IMCSNs (HR, 2.3), tumor diameter greater than 1.5 cm (HR, 3.5), and age older than 65 years (HR, 3.1; reference, < 50 years). CONCLUSIONS: Patients with IMCSNs have worse survival due to distant metastasis. The clinically relevant predictive factor for distant metastasis is tumor larger than 1.5 cm. According to the authors' current protocol, IMCSN biopsy is performed for patients younger than 70 years who have a tumor larger than 1.5 cm, with the cardiotoxicity of the adjuvant IMCRT weighed against the survival benefit.

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. First, the CT and the CBCT scans were registered on bones. Subsequently, breast-contour data were generated. The CBCT contours were analyzed in 3D in terms of deviations (mean and standard deviation) relative to the contour of the CT scan for the upper medial, lower medial, upper lateral, and lower lateral breast quadrants, and the axilla. RESULTS: Regional systematic and random standard deviations of the breast quadrants varied between 1.5 and 2.1 mm and 1.0-1.6 mm, respectively, and were larger for the axilla (3.0 mm). An absolute average shape change of  ≥4.0 mm in at least one region was present in 21/71 fractions (30%), predominantly in breast volumes > 800 cc (p = <0.01). Furthermore, seroma was associated with larger shape changes (p = 0.04). CONCLUSIONS: Breast-shape variability varies between anatomic locations. Changes in the order of 4 mm are frequently observed during RT, especially for large breasts. This should be taken into account in the development of protocols for partial breast irradiation and boost treatment.

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). Multivariable analyses were performed using Cox proportional hazards models. RESULTS: 1922 patients with a median age of 70 years were analyzed. The 5- and 10- years LRR rates were 2% and 3% respectively. In multivariable analysis there was no significant factor influencing LRR risk. Patients with low risk tumors (node negative patients with T1 and ER positive, grade 1 or 2) had lower risk of DM (HR 0.26) and better OS (HR 0.65) compared to patients with higher risk tumors (grade 3 and/or node positive). CONCLUSION: In elderly breast cancer patients the risk of LRR and DM is low. In patients with less favorable characteristics the risk of LRR is equally low, with a higher risk to develop DM and worse OS. Treatment in the low risk group may be minimized, while for the higher risk group adjuvant treatment could be intensified.

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. RESULTS: 70 patients with a median follow-up of 23 months (3-44 months) were evaluated. The overall postoperative infection rate was 11%. At 1, 2 and 3 years of follow-up respectively 89%, 98% and 100% of patients had no or mild induration-fibrosis. Fibrosis was only found in a small volume of the breast. The global cosmetic outcome was good to excellent in 77% at 6 months to 100% at 3 years. Two patients developed a local recurrence. CONCLUSION: Our first results show limited fibrosis in a small volume and good to excellent cosmetic outcome. In selected patients, preoperative radiotherapy appears to be a good option for breast conserving therapy.

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.

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. Primary tumor FDG uptake was evaluated and compared with clinical and histopathological characteristics. Presence of locoregional and distant metastases was assessed and compared with conventional imaging procedures. RESULTS: The primary tumor was visible with PET/CT in 54 (87%) of 62 patients, increasing from 59% (10/17) in tumors ≤ 10 mm to 98% (44/45) in tumors over 10 mm. All triple negative and HER2-positive tumors and 40/48 (83%) ER-positive/HER2-negative tumors were visualized. Sensitivity and specificity of PET/CT in the detection of axillary metastases were 73% and 100%, respectively. PET/CT depicted periclavicular nodes in two patients. Of 12 distant lesions, one was confirmed to be a lung metastasis, three were false positive, and eight were new primary proliferative lesions. CONCLUSION: Using optimal imaging acquisition, the majority of T1 breast carcinomas can be visualized with PET/CT. Specificity in the detection of axillary metastases is excellent, but sensitivity appears to be limited. Additional whole body imaging has a low yield in this specific patient group.

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. Retrospectively, heart registrations were performed for cone-beam computed tomography (CBCT) to planning CT. Further, breast-surface registrations were performed for a surface, captured concurrently with CBCT, to planning CT. The resulting setup errors were compared with linear regression analysis. Furthermore, geometric uncertainties of the heart (systematic [Σ] and random [σ]) were estimated relative to the surface registration. Based on these uncertainties planning organ at risk volume (PRV) margins for the heart were calculated: 1.3Σ-0.5σ. RESULTS: Moderate correlation between surface and heart setup errors was found: R(2)=0.64, 0.37, 0.53 in left-right (LR), cranio-caudal (CC), and in anterior-posterior (AP) direction, respectively. When surface imaging would be used for monitoring, the geometric uncertainties of the heart (cm) are [Σ=0.14, σ=0.14]; [Σ=0.66, σ=0.38]; [Σ=0.27, σ=0.19] in LR; CC; AP. This results in PRV margins of 0.11; 0.67; 0.25 cm in LR; CC; AP. CONCLUSION: When DIBH-RT after breast-conserving surgery is guided by the breast-surface position then PRV margins should be used to take into account the heart-position variability relative to the breast-surface.