RPS 1802 - Breast cancer treatment monitoring

Purpose:

To evaluate the accuracy of image-guided localisation and removal of lymph nodes containing known metastases in breast cancer patients treated with neoadjuvant chemotherapy (NACT).

Methods and materials:

64 patients with breast cancer and nodal metastases who underwent NACT between 2017 and 2019 were prospectively enrolled. A clip was placed in the sampled node. After NACT, patients underwent sentinel lymph node (SLN) dissection, removal of the clipped node (CN), and subsequent axillary lymphadenectomy (ALND). Pathological results of SLN and CN were compared to ALND to assess the false-negative rate (FNR).

Results:

Axillary pathological complete response at ALND was 43,8%.

FNR of SLN was 25%, with 9 false-negative (FN) events in 36 patients with residual disease. In 6/9 patients with FN SLNs, the CN contained metastases, resulting in an FNR of 8.3%.

Basing on the number of abnormal nodes on initial staging, in patients with 1-3 abnormal nodes (21 patients) residual disease was identified in 10 patients at ALND (47,6%). The SLN didn’t reveal metastases in 4/10 patients (FNR=40%) while the CN didn’t reveal metastases in 1 patient (FNR=10%). In >4 abnormal nodes (43 patients), the FNRs of SLN and CN were 19,2% and 7,7%, respectively.

According to radiological response to NACT, in patients with complete radiological response (cRR) (38 patients), the FNR of SLND was 35.3% (6 FN events in 17 patients with residual disease). In 4/6 patients with FN SLNs, the CN contained metastases, with an FNR of 11,7%. In patients without cRR (26 patients), the FNRs of SLN and CN were 15.8% and 5.3%, respectively.

Conclusion:

CN could improve accuracy of axillary staging in node-positive patients who received NACT, especially in N1-stage and in patients with cRR.

Limitations:

Nodal-stage on initial staging.

Ethics committee approval

The study was approved by an ethics committee.

Funding:

No funding was received for this work.

Purpose:

To evaluate treatment response based on diffusion-weighted imaging (DWI) after neoadjuvant systemic treatment (NST). DWI score based on signal patterns on DWI were compared to RECIST-based evaluation.

Methods and materials:

Breast cancer patients who underwent dynamic contrast-enhanced (DCE) MRI and received NST followed by surgery between 2014 and 2019 (n=116) were analysed.

MRI protocols were as follows: T1WI, T2WI, DWI (TR/TE=7000/62 ms; b=0, 1000 sec/mm2), and DCE-MRI performed on 3.0 Tesla scanner (Siemens AG, Erlangen, Germany) with 18 or 16 channel dedicated breast coils. The MRIs were retrospectively evaluated by two radiologists with 20 and 3 years experience of breast MRI, and the target lesions were given a 3-point score . The RECIST-based evaluation was further classified into 3 groups (PD, SD, PR/near CR/CR).

Pathological evaluation: pCR was defined as no residual invasive or non-invasive cancer in breast tissue on histopathology from surgical resection (in situ lesion was allowed). Statistical analysis was performed with MedCalc. The diagnostic performance of DWI parameters in discriminating pCR was assessed using a receiver operating characteristic (ROC) analysis. For RECIST-based criteria, they were grouped as pCR or non-pCR.

Results:

Among 116 cases, 40.5% (47/116) achieved pCR while 59.5% (69/116) were categorised as non-pCR on pathology. The DWI score was strongly associated with residual disease. ROC analysis showed area under the ROC (AUC) of 0.96 (95% confidence interval: 0.91-0.99 ). ROC analysis of RECIST-based evaluation showed AUC of 0.70 (95% Confidence interval: 0.60-0.78).

Conclusion:

DWI-based evaluation of residual disease is a useful approach of breast cancer following NST.

Limitations:

Visual assessment.

Ethics committee approval

This study protocol was approved by our institutional review board.

Funding:

No funding was received for this work.

Purpose:

Sarcopenia is widely considered a predictor of poor survival and toxicity in breast cancer patients. The aim of this study was to evaluate if there is pectoralis muscle area (PMA) variation, reflecting a loss of skeletal muscle mass, on consecutive MRI examinations during neoadjuvant chemotherapy.

Methods and materials:

A total of n=110 consecutive patients (mean age 56±11years) who were treated with NAC for histologically proven primary breast cancer between January 2017 and January 2019, and in whom tumour response was checked with standard breast MRI, were included. Two radiologists calculated the pectoralis muscle cross-sectional area before and after NAC.

Results:

The time between the two MRI examinations, before starting NAC, and after completion of three cycles of NAC was 154,8±34 days. PMA calculated pre-NAC (8,14 cm²) was larger than PMA calculated post-NAC (7,03 cm²), (p<0.001). According to RECIST criteria, there were no significant differences between responders (complete or partial response) and no responders (p=0.362). The multivariate regression analysis did not show any significant relationships between ΔPMA and age, the time between MRI exams, estrogen and progesterone receptor status, human epidermal growth factor receptor status (HER-2), Ki-67 expression, lymph nodes status, RECIST criteria, or histological type and grade. Inter-reader (k=0.72) and intra-reader agreement (0.69 and 0.71) in PMA assessment were good.

Conclusion:

Pectoralis muscle mass variation, reflecting loss of skeletal muscle mass, in breast cancer patients undergoing NAC can be estimated directly on standard breast MRI.

Limitations:

Known limitations are the retrospective nature of the study and the lack of a control-group.

Ethics committee approval

The study was approved by our institutional review board. Written informed consent was obtained.

Funding:

No funding was received for this work.

Purpose:

To analyse the different shrinkage pattern of breast tumors in magnetic resonance imaging (MRI) after neoadjuvant chemotherapy (NAC) and to evaluate the efficacy of different shrinkage pattern in chemotherapy.

Methods and materials:

Data from 50 patients who were diagnosed with unilateral breast cancer underwent NAC before surgery after the eighth cycle of NAC was analysed retrospectively. All patients underwent MRI scan with contrast enhancement. The shrinkage pattern was classified into 3 categories: concentric shrinkage, fragment-like shrinkage, and mixed shrinkage. All the patients were divided into pathological complete response (pCR) group and N-pCR group according to the histopathologic tumour response. The χ² test were used to compare the baseline characteristics of pCR and N-pCR groups, as well as the tumour enhancement pattern and shrinkage pattern of the molecular types. Associations were evaluated using binary logistic regression models.

Results:

16 patients achieved pCR and 34 patients had a residual disease (N-pCR). Age, menopausal status, tumour size, lymph node, T stage, molecular typing, ER, PR, ki-67 status, and tumour enhancement mode on MRI showed no significance between pCR and N-pCR groups (all p>0.05), while only HER2 status and shrinkage pattern a significant difference (p<0.05 in both). Interobserver agreement regarding shrinkage pattern was moderate after NAC (Kappa value 0.719). There were no statistically significant differences in tumour shrinkage pattern and MRI tumour enhancement among the molecular types (all p >0.05). There were statistically significant differences in MRI tumour enhancement in the tumour shrinkage pattern (p<0.05). Logistic model showed that tumour shrinkage pattern after NAC and HER2 status were independent factors for predicting pCR.

Conclusion:

Shrinkage pattern and HER2 status can be independent factors for predicting pCR.

Limitations:

A retrospective study.

Ethics committee approval

LL-KT-201801162.

Funding:

Shenzhen science and technology research and development fund (JCYJ20180305164740612).

Purpose:

To assess the value of ¹⁸F-FDG PET/CT in predicting the presence of axillary lymph node metastasis (ALNM) and their response to neoadjuvant systemic therapy (NST) in breast cancer patients.

Methods and materials:

We analysed 37 patients with breast cancer that underwent ¹⁸F-FDG PET/CT prior to NST. Maximum standardised uptake values of the primary tumour (SUV-T) and the most FDG-avid lymph node (SUV-LN) and their ratio (NT ratio) were calculated. Patients with and without suspicious ALNM based on prior imaging were compared regarding their SUV values. ALNM response following NST was classified according to the Pinder classification. Patients were defined as responders (Pinder 1-3) and non-responders (Pinder 4). The association of SUV_max with ALNM response was assessed using ROC analyses.

Results:

Of 37 patients, 25 (68%) had suspicion for ALNM. Patients with suspected ALNM showed significantly higher SUV-LN (1.5 vs. 6.1) and NT ratio (0.3 vs. 1.0), but no significant difference in SUV-T (6.0 vs. 8.3) was found. Non-significant differences between responders and non-responders of SUV-T (7.5 vs. 8.2), SUV-LN (5.6 vs. 5.1), and NT ratio (0.9 vs. 0.7) were found. The AUCs for SUV-T, SUV-LN, and NT ratio were 0.544, 0.630, and 6.11, respectively. An SUV-LN cutoff value of 3.5 had a sensitivity of 75% and a specificity of 49% in identifying patients who responded to NST.

Conclusion:

¹⁸F-FDG PET/CT showed promising results in predicting ALNM and their response to NST in breast cancer patients.

Limitations:

These results are preliminary, hence the low sample size.

Ethics committee approval

The need for informed consent was waived by a local ethics committee.

Funding:

No funding was received for this work.

Purpose:

To evaluate the effect of breast MRI on overall survival (OS) and disease-free survival (DFS) of patients with invasive breast cancer in the Netherlands.

Methods and materials:

We selected all women from the nationwide cancer registry diagnosed with invasive breast cancer (a) between 2011-2013 for the OS-cohort and (b) in the first quarter of 2012 for the DFS-cohort. The study population was divided into a MRI and non-MRI group. In addition, subgroups were created according to breast cancer subtype: invasive carcinoma of no special type (NST) versus invasive lobular carcinoma (ILC). OS and DFS were compared between the MRI and non-MRI group using the Kaplan-Meier method and the log-rank test. Cox proportional hazard regression analysis was performed to estimate hazard ratio (HR) with a 95% confidence interval (CI). To account for missing data, multiple imputation was performed.

Results:

Of the 31,756 patients included in the OS-cohort (70% non-MRI and 30% MRI), 27,752 (87%) were diagnosed with invasive carcinoma NST and 4,004 (13%) with ILC. Multivariable Cox regression showed that breast MRI had a tendency towards better OS (HR 0.91, 95%-CI 0.74-1.11) and was statistically significant for patients aged >50 years (overall). Of the 2,464 patients included in the DFS-cohort (72% non-MRI and 28% MRI), 2,161 (88%) were diagnosed with invasive carcinoma NST and 303 (12%) with ILC. Multivariable Cox regression analysis showed that breast MRI was not significantly associated with DFS (HR 1.16, 95%-CI 0.81-1.67).

Conclusion:

Breast MRI was not significantly associated with an improved DFS and revealed a tendency towards an improved OS, which was only significant for patients aged >50.

Limitations:

Retrospective and observational design.

Ethics committee approval

n/a

Funding:

No funding was received for this work.

Purpose:

To investigate the accuracy of MRI in evaluating response to neoadjuvant chemotherapy (NAC) in primary breast cancer and to determine if the presence of DCIS/LCIS can influence the accuracy.

MRI has a high specificity for the correct detection of residual tumour after NAC, but low sensitivity (correct identification of complete pathological response (pCR) PPV 48% has been reported).

Methods and materials:

A cohort of 461 consecutive patients who received NAC in a single cancer centre (2007–2019) with post-NAC pre-surgery MRI and surgery pathology data were analysed. ‘Gold Standard’ for the response was pCR in the surgical specimen. Radiological complete response (rCR) was defined as 0 mm and non-rCR defined as ≥1 mm, using maximum tumour diameter on MRI.

Results:

In the whole cohort, MRI sensitivity (probability of identifying a pCR from rCR)=71.0% (88/124), and specificity (probability of correctly identifying non-pCR from non-rCR)=81.0% (273/337).

The presence of DCIS/LCIS in the surgical sample reduces the accuracy of MRI assessment, sensitivity by 24.8% (with=53.1% vs without=77.9%), and specificity by 2.4% (with=78.6% vs without=81.0%), increasing overestimation of disease size. False-negative rate (probability of rCR incorrectly identifying pCR) is 46.9% with DCIS/LCIS versus 22.1% without DCIS/LCIS.

Conclusion:

This analysis showed that there is a need to improve the accuracy of MRI assessment of pCR.

There is an urgent need to identify variables which can improve this invaluable tool to optimise treatment planning.

Introducing a volumetric and texture AI-driven analysis may increase the accuracy and confidence of MRI with positive clinical benefit leading to better patient treatment and less invasive approach to surgery.

Limitations:

A retrospective study. Further researches needed.

Ethics committee approval

n/a

Funding:

No funding was received for this work.

Purpose:

To investigate which MRI morphologic criteria can predict residual disease in ALNs in patients who have undergone NAC.

Methods and materials:

From 2017 to 2019, 60 consecutive patients with advanced breast cancer who underwent 1,5 T MRI before and after NAC were retrospectively collected. Pre- and post-NAC MRI were retrospectively analysed by two dedicated radiologists in consensus, blinded to histological results, evaluating both quantitative (number and diameter) and qualitative criteria (irregular margins, absence of fatty hilum, cortical thickness>3mm, perifocal oedema, rim enhancement, and asymmetry comparing with contralateral side) related to ALNs. ALNs status was evaluated by sentinel ALN biopsy or axillary dissection and nodal pathological response classified according to Pinder’s criteria [complete response (pCR) versus no-complete response (no-pCR)]. Statistical analysis (Chi-square or Fisher’s exact tests for categorical variables, non-parametric Mann-Whitney test for continuous variables) was performed to compare pCR versus no-pCR cases.

Results:

At baseline MRI, no-pCR cases ALNs were characterised by loss of fatty hilum (93.3% versus 44.4% in pCR, p=0.02), presence of rim enhancement (86.7% versus 11.1% in pCR, p=0.001), asymmetry (93.3% versus 44,4% in pCR, p=0.02), average cortical thickness significantly larger (9.5 versus 3.7 mm, p=0.004) than pCR cases. At post-NAC MRI, average cortical thickness was significantly (p=0.01) larger in no-pCR patients compared to pCR (4.5 versus 1.8 mm). Considering as suspicious ALN with at least one of the above characteristics, MRI sensitivity, specificity, positive and negative predictive values, and accuracy for assessing ALNs response were 88.2%, 77.8%%, 88.2%, 77.8%, and 84.6%, respectively.

Conclusion:

Based on our results, supporting the use of MRI in assessing nodal response after NAC, abnormal ALNs cortical thickness seems to be the most reliable parameter associated to no-pCR.

Limitations:

Small sample, monocentric study.

Ethics committee approval

n/a

Funding:

No funding was received for this work.

Purpose:

To determine whether a classifier based on two US parameters (volume and stiffness) is predictive of treatment responses from the first courses of neoadjuvant chemotherapy (NAC).

Methods and materials:

Prospective US analysis was performed in patients with breast cancer qualified for NAC, before and 7 days after the first four courses of NAC. US examinations with strain sonoelastography were performed using linear transducer L14-5. Tumour volume and tumour stiffness (using Tsukuba scale) were evaluated. The resistant malignant cells [RMC] (ranging from 0–100%) were assessed by a pathologist postoperatively. Histopathological examination classifies tumours as responding (RT) and non-responding (N-RT). RT included those with a reduction in cellularity ≥30% while N-RT was <30%. Correlation analysis, univariate, and multivariate logistic regression analysis were used for statistical assessment.

Results:

A total of 42 breast cancer in 30 patients (mean age 56.4y) were examined. A statistically significant correlation was found between stiffness, volume, and RMC (p<0.05) after 2, 3, and 4 courses of NAC. In logistic regression, the best results were after the 3^rd course of NAC. Using only stiffness as a prognostic parameter, we obtained a sensitivity of 37%, specificity of 87%, PPV 70%, NPV 63%, and for volumes respectively: 47%, 77%, 74%, and 67%. The classifier using both parameters showed a sensitivity of 73%, specificity 75%, PPV 68%, and NPV 78%.

Conclusion:

The use of two US parameters, volume and stiffness, are highly predictive of tumour response after the 3^rd NAC cycle and performed better than single parameters.

Limitations:

A small group.

Ethics committee approval

The study was approved by the institutional bioethical review board of each participating institution.

Funding:

Purpose:

To assess the long-term performance of wire-free SCOUT localisation in the breast and axilla in neoadjuvant chemotherapy patients prior to surgery.

Methods and materials:

Adult female breast cancer patients had wire-free SCOUT localisation (WFL) prior to neoadjuvant treatment and surgery between February 13, 2017, and July 3, 2019. Electronic medical record and surgical pathology determined the study endpoints.

Primary: Rate of successful surgery using WFL prior to NACT.

Secondary: Number of days to surgery, success rate of WFL placement, stability, and device-related complications.

Results:

38 WFL (16 breast and 22 axilla) were successfully placed prior to NACT in 34 patients, age 29-74 (mean 52) years. All (100%) underwent definitive breast cancer surgery after 32 to 516 (average 198) days. Standard imaging (MG, US, MRI, CT) was used to monitor response to NACT, specimen radiograph and surgical pathology reports documented no significant SCOUT migration (>5mm), no adverse events, and no obscuration of target tissue in 16/16 MRI exams.

Conclusion:

Since longer-duration SCOUT WFL lead to successful surgery without adverse events or limitations on MRI, this study suggests the possibility of a clinically relevant paradigm shift regarding the timing of preoperative localisation. WFL prior to NACT response maintains flexible options for the surgical team, including de-escalation of breast or axillary lymph node surgery.

Limitations:

This single-institution pilot was limited by a small study size. A multi-centre study including other WFL devices (TAG, MAGSEED, SmartClip) may provide further generalised knowledge for breast treatment teams.

Ethics committee approval

This prospective pilot study was approved by the institutional review board and written informed consent was obtained.

Funding:

No funding was received for this work.