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Background: The nodal positivity rate after neoadjuvant chemotherapy (ypNþ) in patients with clinically node-negative (cN0) breast cancer is low, especially in those with a pathological complete response of the breast. The aim of this study was to identify characteristics known before surgery that are associated with achieving ypN0 in patients with cN0 disease. These characteristics could be used to select patients in whom sentinel lymph node biopsy may be omitted after neoadjuvant chemotherapy. Methods: This cohort study included patients with cT1-3 cN0 breast cancer treated with neoadjuvant chemotherapy followed by breast surgery and sentinel node biopsy between 2013 and 2018. cN0 was defined by the absence of suspicious nodes on ultrasound imaging and PET/CT, or absence of tumour cells at fine-needle aspiration. Univariable and multivariable logistic regression analyses were performed to determine predictors of ypN0. Results: Overall, 259 of 303 patients (85.5 per cent) achieved ypN0, with high rates among those with a radiological complete response (rCR) on breast MRI (95·5 per cent). Some 82 per cent of patients with hormone receptor-positive disease, 98 per cent of those with triple-negative breast cancer (TNBC) and all patients with human epidermal growth factor receptor 2 (HER2)-positive disease who had a rCR achieved ypN0. Multivariable regression analysis showed that HER2-positive (odds ratio (OR) 5·77, 95 per cent c.i. 1·91 to 23·13) and TNBC subtype (OR 11·65, 2·86 to 106·89) were associated with ypN0 status. In addition, there was a trend toward ypN0 in patients with a breast rCR (OR 2·39, 0·95 to 6·77). Conclusion: The probability of nodal positivity after neoadjuvant chemotherapy was less than 3 per cent in patients with TNBC or HER2-positive disease who achieved a breast rCR on MRI. These patients could be included in trials investigating the omission of sentinel node biopsy after neoadjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Introduction 18 F-FDG PET/CT has high positive predictive value for the detection of avid lymph node metastases in breast cancer patients. We analysed the effect of upstaging lymph nodes by PET/CT on short-term outcome in stage II/III breast cancer patients. Patients and methods A total of 278 stage II/III primary breast cancer patients (mean age 48.9 years, range 19–75 years) were re-staged with 18 F-FDG PET/CT before start of pre-operative systemic treatment (PST). Patients were divided in three groups based on risk for local recurrence: a low – (T2N0), intermediate – (T0-2N1 and T3N0) and a high-risk group (T0-3N2–3, T3N1 and T4). Within these groups we looked at local recurrence-free survival (LRFS), recurrence-free survival (RFS) and overall survival (OS) within the first 3 years of follow-up. Results With a median follow-up (FU) of 50 months the RFS, LRFS and OS were 87%, 88% and 92% respectively for the whole group. PET/CT upstaged 43 patients from the low- and intermediate risk group to the high-risk group, based on detection of ≥4 avid axillary nodes or occult N2/3-disease. Patients upstaged with PET/CT had more events for all three analyses compared to the original risk groups, which resulted in a significantly worse RFS (69.8%; p = 0.03) a nearly significantly worse LRFS (p = 0.052) and no effect in OS (p = 0.433). Discussion Additional PET/CT staging allows breast cancer patients to be treated according to the true stage, still stage II/III breast cancer patients upstaged to N2/3 by PET/CT have worse short-term outcome, despite adjustment of treatment, than patients staged high-risk with conventional imaging. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Risk factors for local recurrence in breast cancer after breast conserving therapy (BCT) differ from those for local recurrence after mastectomy. To better guide optimal treatment of individual patients, it is desirable to identify patients at high risk for local recurrence. Several clinical and histopathologic factors, such as young age and presence of ductal carcinoma in situ, are known to be predictors for local recurrence after BCT. After mastectomy, lymph node status and tumor size are dominant risk factors for local recurrence. The results of recent expression profiling studies have explained differences in prognosis and risk for local recurrence and also explained response to different therapies (adjuvant systemic therapy and radiotherapy). Because of the variation in different subtypes of breast cancer and the difference in amount of tumor burden remaining after surgery, finding robust predictive profiles is complex. In this review, we describe the predictive and prognostic factors for local recurrence after mastectomy and BCT and also describe the role of radiosensitivity in local recurrence. [Copyright &y& Elsevier]

The article presents a study which aims to redesign the processes done at the computer tomography (CT) department in the Academic Medical Center in Amsterdam, the Netherlands, to decrease the access time for the CT-scan and simultaneously increase utilization level. Results have suggested that the promising and most feasible opportunity is to reallocate the insertion of intravenous access lines to a preparation room to reduce access time and improve utilization rate.

Background: Poly (ADP-ribose) Polymerase (PARP) inhibitors are promising novel radiosensitisers. Pre-clinical models have demonstrated potent and tumour-specific radiosensitisation by PARP inhibitors. Olaparib is a PARP inhibitor with a favourable safety profile in comparison to clinically used radiosensitisers including cisplatin when used as single agent. However, data on safety, tolerability and efficacy of olaparib in combination with radiotherapy are limited.Methods: Olaparib is dose escalated in combination with radical (chemo-)radiotherapy regimens for non-small cell lung cancer (NSCLC), breast cancer and head and neck squamous cell carcinoma (HNSCC) in three parallel single institution phase 1 trials. All trials investigate a combination treatment of olaparib and radiotherapy, the NSCLC trial also investigates a triple combination of olaparib, radiotherapy and concurrent low dose cisplatin. The primary objective is to identify the maximum tolerated dose of olaparib in these combination treatments, defined as the dose closest to but not exceeding a 15% probability of dose limiting toxicity. Each trial has a separate dose limiting toxicity definition, taking into account incidence, duration and severity of expected toxicities without olaparib. Dose escalation is performed using a time-to-event continual reassessment method (TITE-CRM). TITE-CRM enables the incorporation of late onset toxicity until one year after treatment in the dose limiting toxicity definition while maintaining an acceptable trial duration. Olaparib treatment starts two days before radiotherapy and continues during weekends until two days after radiotherapy. Olaparib will also be given two weeks and one week before radiotherapy in the breast cancer trial and HNSCC trial respectively to allow for translational research. Toxicity is scored using common terminology criteria for adverse events (CTCAE) version 4.03. Blood samples, and tumour biopsies in the breast cancer trial, are collected for pharmacokinetic and pharmacodynamic analyses.Discussion: We designed three parallel phase 1 trials to assess the safety and tolerability of the PARP inhibitor olaparib in combination with radical (chemo-)radiotherapy treatment regimens. PARP inhibitors have the potential to improve outcomes in patients treated with radical (chemo-)radiotherapy, by achieving higher locoregional control rates and/or less treatment associated toxicity.Trial Registration: ClinicalTrials.gov Identifiers: NCT01562210 (registered March 23, 2012), NCT02227082 (retrospectively registered August 27, 2014), NCT02229656 (registered September 1, 2014). [ABSTRACT FROM AUTHOR]

Background: Risk for locoregional recurrence (LRR) in breast cancer depends on tumor size and on number and location of tumor-positive locoregional nodes. Postoperative irradiation of chest wall and/or locoregional nodes is advised in patients at high risk for LRR, but remains controversial in patients at intermediate risk. Because the number of tumor-positive axillary nodes in patients treated with neoadjuvant chemotherapy (NAC) can no longer be determined from the axillary lymph node dissection (ALND) and conventional staging of N3-disease with ultrasound is inaccurate, planning of radiotherapy in these patients is hampered. The aim of the present study was to assess the accuracy of 18F-FDG PET/CT for locoregional staging in stage II-III breast cancer patients scheduled for NAC. Second, we wished to assess the value of pre-chemotherapy PET/CT in estimating the risk for LRR and determining chest wall and/or locoregional radiotherapy indication, based on the detection of ≥4 FDG-avid axillary nodes or occult N3-disease. Methods: 278 patients underwent PET/CT of the thorax in prone position. Presence and number of FDG-avid nodes were evaluated, blinded for other diagnostic procedures. First, PET/CT findings were compared with histopathology before NAC (ultrasound with fine needle aspiration and/or sentinel lymph node biopsy (SLNB)) to determine the diagnostic accuracy for detection of axillary metastases and newly discovered N3-disease. Second, risk estimation and radiotherapy planning were evaluated with and without PET/CT. Conventional locoregional staging consisted of ultrasound with fine needle aspiration before, SLNB before, and ALND after NAC. Patients were classified as low-risk (cT2N0), intermediate-risk (cT0N1, cT1N1, cT2N1, and cT3N0), or high-risk (cT3N1, cT4, cN2-3, and (y)pN2-3) for LRR. Emphasis was on the number of patients upstaged to the high-risk group by PET/CT, requiring postoperative locoregional irradiation. Results: Sensitivity, specificity, positive predictive value, and negative predictive value in the detection of axillary metastases were 80%, 92%, 98%, and 53%, respectively. Occult lymph node metastases in the internal mammary chain and periclavicular area were detected in 17 (6%) and 25 (9%) patients, respectively. PET/CT detected occult N3-disease in 5 (11%) of 47 low-risk patients. In 116 intermediate-risk patients, PET/CT detected ≥4 FDG-avid nodes in 14 (12%) patients and occult N3-disease in 13 (11%) patients, upstaging 25 (22%) of intermediate-risk patients. In total, 30 (18%) of 278 low- and intermediate-risk patients were upstaged to the high-risk group, requiring chest wall and/or locoregional irradiation. [ABSTRACT FROM AUTHOR]