DCIS knowledge of women choosing between active surveillance and surgery for low-risk DCIS.

BACKGROUND: Ductal carcinoma in situ (DCIS) can progress to invasive breast cancer (IBC), but often never will. As we cannot predict accurately which DCIS-lesions will or will not progress to IBC, almost all women with DCIS undergo breast-conserving surgery supplemented with radiotherapy, or even mastectomy. In some countries, endocrine treatment is prescribed as well. This implies many women with non-progressive DCIS undergo overtreatment. To reduce this, the LORD patient preference trial (LORD-PPT) tests whether mammographic active surveillance (AS) is safe by giving women with low-risk DCIS a choice between treatment and AS. For this, sufficient knowledge about DCIS is crucial. Therefore, we assessed women's DCIS knowledge in association with socio-demographic and clinical characteristics. METHODS: LORD-PPT participants (N = 376) completed a questionnaire assessing socio-demographic and clinical characteristics, risk perception, treatment choice and DCIS knowledge after being informed about their diagnosis and treatment options. RESULTS: 66 % of participants had poor knowledge (i.e., answered ≤3 out of 7 knowledge items correctly). Most incorrect answers involved overestimating the safety of AS and misunderstanding of DCIS prognostic risks. Overall, women with higher DCIS knowledge score perceived their risk of developing IBC as being somewhat higher than women with poorer knowledge (p = 0.049). Women with better DCIS knowledge more often chose surgery whilst most women with poorer knowledge chose active surveillance (p = 0.049). DISCUSSION: Our findings show that there is room for improvement of information provision to patients. Decision support tools for patients and clinicians could help to stimulate effective shared decision-making about DCIS management.

Added value of repeat sentinel lymph node biopsy in FDG-PET/CT node-negative patients with ipsilateral breast cancer recurrence.

PURPOSE: Repeat sentinel lymph node biopsy (rSLNB) has been suggested for axillary staging in clinically node-negative (cN0) patients with ipsilateral breast tumor recurrence (IBTR). Although rSLNB is technically feasible in this group of patients, the clinical value has not been established. We aimed to assess the added value of rSLNB in cN0 patients with IBTR who underwent optimal clinical staging with FDG-PET/CT. METHODS: This retrospective single-center cohort study included 119 patients with IBTR-staged cT1-4N0M0 with FDG-PET/CT who underwent rSLNB between 2006 and 2020. Overall recurrence-free survival (RFS) and overall survival (OS) were calculated for subgroups with tumor-positive, tumor negative, and unsuccessful rSLNB. RESULTS: rSLNB was successful in 79 (66%) of the 119 included patients, of whom 70 (59%) had a tumor negative and 9 (8%) a tumor-positive rSLNB; rSLNB was unsuccessful in the remaining 40 (34%) patients. Patients with a tumor-positive rSLNB had poorer overall 5-year RFS compared to patients with a tumor negative or unsuccessful rSLNB (44% vs. 86% vs. 90%, p = 0.004). Although patients with a tumor-positive rSLNB had worse RFS, the 10-year OS was comparable to a tumor negative or unsuccessful rSLNB (89% vs. 89% vs. 95%, p = 0.701). CONCLUSION: The incidence of a tumor-positive rSLNB in patients with a negative FDG-PET/CT is low and does not change survival. Therefore, in cN0 patients with IBTR who underwent optimal clinical staging with FDG-PET/CT, we support a patient- and tumor-tailored treatment strategy in which rSLNB may be omitted.

Toward omitting sentinel lymph node biopsy after neoadjuvant chemotherapy in patients with clinically node-negative breast cancer.

BACKGROUND: The nodal positivity rate after neoadjuvant chemotherapy (ypN+) 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.

Identifying pathologic complete response of the breast after neoadjuvant systemic therapy with ultrasound guided biopsy to eventually omit surgery: Study design and feasibility of the MICRA trial (Minimally Invasive Complete Response Assessment).

PURPOSE: Improvements in neoadjuvant systemic therapy (NST) for breast cancer patients have led to increasing rates of pathologic complete response (pCR). The MICRA trial (NTR6120) aims at identifying pCR with post-NST biopsies. Here, we report the study design and feasibility. METHODS: The MICRA-trial is a multi-center prospective cohort study. Patients with a pre-NST placed marker and radiologic complete (rCR) or partial response on MRI after NST are eligible for inclusion. Ultrasound guided biopsy of the original tumor area is performed. Pathology results of the biopsies and surgery specimens are compared. The primary endpoint is false-negative rate of biopsies in identifying pCR. RESULTS: During the first year of the trial 58 patients with rCR were included. One patient was a screening failure and excluded for analysis. Twenty-one percent had hormone receptor (HR)+/HER2- tumors, 21% HR+/HER2+ tumors, 18% HR-/HER2+ tumors and 40% TN tumors. Overall pCR was 68%. In seven patients biopsies could not be obtained: in 6 patients, the marker could not be identified on ultrasound in the OR and in 1 patient there were technical difficulties. A median of eight biopsies was obtained (range 4-9). The median of histopathological representative biopsies was 4 (range 1-8). CONCLUSION: Ultrasound guided biopsy of the breast in patients with excellent response on MRI after NST is feasible. Accuracy results of the MICRA trial will be presented after inclusion of 525 patients to determine if ultrasound guided biopsy is an accurate alternative to surgical resection for assessment of pCR after NST.

Major Reduction in Axillary Lymph Node Dissections After Neoadjuvant Systemic Therapy for Node-Positive Breast Cancer by combining PET/CT and the MARI Procedure.

BACKGROUND: Axillary lymph node dissection (ALND) is frequently performed for node-positive (cN+) breast cancer patients. Combining positron emission tomography/computed tomography (PET/CT) before-NST and the MARI (marking axillary lymph nodes with radioactive iodine seeds) procedure after neoadjuvant systemic therapy (NST) has the potential for avoiding unnecessary ALNDs. This report presents the results from implementation of this strategy. METHODS: All breast cancer patients treated with NST at the Netherlands Cancer Institute who underwent a PET/CT and the MARI procedure from July 2014 to July 2017 were included in the study. All the patients underwent tailored axillary treatment according to a protocol based on the combined results of PET/CT before NST and the MARI procedure after NST. With this protocol, patients showing one to three FDG-avid axillary lymph nodes (ALNs) on PET/CT (cN<4) and a tumor-negative MARI node receive no further axillary treatment. All cN (<4) patients with a tumor-positive MARI node receive locoregional radiotherapy, as well as patients with four or more FDG-avid ALNs [cN(4+)] and a tumor-negative MARI node after NST. An ALND is performed only for cN(4+) patients with a tumor-positive MARI node. RESULTS: The data of 159 patients who received a PET/CT before NST and a MARI procedure after NST were analyzed. Of these patients, 110 had one to three FDG-avid ALNs and 49 patients showed four or more FDG-avid ALNs on PET/CT before NST. For 130 patients (82%), ALND was omitted. Locoregional radiotherapy was administered to 91 patients (57%), and 39 patients (25%) received no further axillary treatment. CONCLUSION: Combining pre-NST axillary staging with PET/CT and post-NST staging with the MARI procedure resulted in an 82% reduction of ALNDs for cN + breast cancer patients.

[Radiofrequency ablation of colorectal metastases to the liver: results since the first application in the Netherlands]. / Radiofrequente ablatie van colorectale levermetastasen: resultaten vanaf de eerste toepassing in Nederland.

OBJECTIVE: To provide an overview of the morbidity, mortality and survival following the introduction of radiofrequency ablation (RFA) of colorectal liver metastases in the Netherlands. DESIGN: Prospective, descriptive study. METHOD: Between June 1999 and December 2003 in eight hospitals in the Netherlands, 87 patients treated by RFA for colorectal liver metastases were included in the study. The outcome measures were morbidity, 30-day mortality and the percentage local recurrence. RESULTS: In 104 RFA procedures, 199 metastases were ablated; 31 procedures were performed percutaneously and 73 by laparotomy. In 29 procedures, RFA was combined with partial liver resection. The overall postoperative morbidity rate was 19% and the RFA-related morbidity was 14%. 1 patient died following right hemihepatectomy and RFA in the remaining parenchyma (mortality: 1%). Median survival following RFA was 25 months, with a median progression-free survival of 13 months. The overall local recurrence rate was 46%. Since January 2004, this percentage has decreased to approximately 6. Diameter and central location of the metastases were independent risk factors for the development of a local recurrence. CONCLUSION: RFA is an alternative treatment for patients who are not eligible for partial liver resection. The high local recurrence rate in this series reflects the limited experience with this technique during its introduction in the Netherlands. In specialised centres the percentage local recurrence is now 5. Treatment by RFA should always be weighed against the option of partial liver resection and possible (neoadjuvant) chemotherapy. RFA should therefore preferably be carried out in a centre with expertise in the field of liver surgery.

Locoregional therapies of liver metastases in a rat CC531 coloncarcinoma model results in increased resistance to tumour rechallenge.

BACKGROUND: Locoregional treatments like photodynamic therapy (PDT), radiofrequency ablation (RFA) or hepatic artery infusion (HAI) of chemotherapeutics may be applied for unresectable colorectal liver metastases. We evaluated the effect of these treatments on the immune response in a rat colon tumour liver metastases model. METHOD: Wag/Rij rats were inoculated at day 0 with CC531 tumour cells at two sites in the liver. At day 15, one of two tumours was treated with RFA or PDT, or the liver was treated by HAI. Twelve days later (day 27), rats were rechallenged locally with CC531 cells in the liver or systemically with CC531 cells in the femoral vein. At day 42, tumour growth in liver and lungs was determined. RESULTS: RFA, PDT and HAI were very effective in liver tumour eradication, but following RFA or PDT there was no inhibitory effect on untreated nearby liver tumours. Outgrowth after local rechallenge was, however, significantly inhibited in RFA-, PDT- and HAI-treated rats, whereas all control rats showed outgrowth of a third liver tumour. After systemic rechallenge, control rats developed lung metastases whereas treated rats did not, but this difference was not statistically significant. CONCLUSION: These results show that following PDT, RFA and HAI resistance to local and possibly systemic tumour rechallenge is increased. This may be partly due to the induction or enhancement of a cellular immune response.

Adverse effects of radiofrequency ablation of liver tumours in the Netherlands.

BACKGROUND: Radiofrequency ablation (RFA) is a new treatment for liver tumours. Complications encountered after RFA in the Netherlands were evaluated in the present study. METHODS: Between June 1999 and November 2003 patients undergoing RFA of irresectable liver tumours in eight medical centres were registered prospectively. RESULTS: One hundred and forty-three RFA procedures were performed in 122 patients. RFA was combined with partial hepatectomy in 37 instances. Death occurred after two procedures (1.4 per cent), and was mainly due to concomitant partial hepatectomy. A total of 19 major complications occurred after ten procedures, including biliary tract damage (seven patients), liver failure (four), hepatic abscess (three), peritoneal infection (two), intrahepatic haematoma (one), hepatic artery aneurysm (one) and pulmonary embolism (one). Twenty-four minor complications were related to concomitant partial hepatectomy or laparotomy. The overall complication rate was 20.3 per cent and the rate of complications related directly to RFA was 9.8 per cent. CONCLUSION: The procedure-specific complication rate was almost 10 per cent and it is recommended that RFA should be performed only by an experienced team comprising a hepatobiliary surgeon, gastroenterologist, hepatologist and interventional radiologist. Biliary stricture, hepatic vascular damage and hepatic abscesses were the most common major complications.