Monitoring neoadjuvant chemotherapy in breast cancer patients: Improved MR assessment at 3 T?

Purpose:

To investigate possible improvements in predicting the response to neoadjuvant chemotherapy (NAC) at 3 T for locally advanced breast cancer (LABC).

Materials and Methods:

Dynamic contrast‐enhanced magnetic resonance (DCE‐MR) images acquired before and during NAC were retrospectively analyzed in 85 patients. Tumor volume and diameter, three volumes based on the shape of the enhancement curve, relative signal intensity, area under the curve, and the signal‐to‐noise ratio were extracted. Differences between responders and nonresponders at the same and between MR timepoints during treatment were evaluated.

Results:

A higher signal‐to‐noise ratio was observed on 3 T images compared to 1.5 T, and 3 T revealed more significant findings related to response compared to 1.5 T. The DCE‐MRI‐derived volume parameters were the earliest predictors of response at both 1.5 and 3 T.

Conclusion:

Our results show that 3 T provides an improved assessment of the response to NAC in LABC patients, where the MR determined tumor volume reduction before the second cycle of NAC was the strongest and earliest predictor of a response. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

Assessment of breast cancer response to neoadjuvant chemotherapy: is volumetric MRI a reliable tool?

The purpose of this study was to evaluate the reliability of volumetric magnetic resonance imaging (MRI) in breast cancer size assessment before, during and after neoadjuvant chemotherapy (NAC).Volumetric MRI measures performed on 15 patients with breast cancer were compared with volumes reckoned upon mean lesional diameters, using the same MRI data. Concordance correlation coefficient (CCC), Bland & Altman plots, RECIST evaluation and Cohen's Kappa were assessed, to evaluate the agreement between the two methods.CCC was computed before (0.9357), during (0.8053) and after (0.7499) NAC, in all examinations pooled together (0.8617), and on final tumor volume as a percentage of baseline volume (0.9224). In 2/15 (13.3%) cases RECIST assessment was different. Cohen's Kappa was 0.787 (CI_95% = 0.513-1.062).In summary, volumetric MRI is a reliable tool to assess breast cancer size before, during and after NAC. Further investigations are needed to understand whether improvements in surgical planning are feasible.     

Investigating the prediction value of multiparametric magnetic resonance imaging at 3 T in response to neoadjuvant chemotherapy in breast cancer

Objective

To explore the predictive value of parameters derived from diffusion-weighted imaging (DWI) and contrast-enhanced (CE)-MRI at different time-points during neoadjuvant chemotherapy (NACT) in breast cancer.

Methods

Institutional review board approval and written, informed consent from 42 breast cancer patients were obtained. The patients were investigated before and at three different time-points during neoadjuvant chemotherapy (NACT) using tumour diameter and volume from CE-MRI and ADC values obtained from drawn 2D and segmented 3D regions of interest. Prediction of pathologic complete response (pCR) was evaluated using the area under the curve (AUC) of receiver operating characteristic analysis.

Results

There was no significant difference between pathologic complete response and non-pCR in baseline size measures (p?>?0.39). Diameter change was significantly different in pCR (p?<?0.02) before the mid-therapy point. The best predictor was lesion diameter change observed before mid-therapy (AUC?=?0.93). Segmented volume was not able to differentiate between pCR and non-pCR at any time-point. The ADC values from 3D-ROI were not significantly different from 2D data (p?=?0.06). The best AUC (0.79) for pCR prediction using DWI was median ADC measured before mid-therapy of NACT.

Conclusions

The results of this study should be considered in NACT monitoring planning, especially in MRI protocol designing and time point selection.

Key Points

? Mid-therapy diameter changes are the best predictors of pCR in neoadjuvant chemotherapy. ? Volumetric measures are not strictly superior in therapy monitoring to lesion diameter. ? Size measures perform as a better predictor than ADC values.

     

The ‘twinkle’ artifact — A novel method of clip identification to facilitate targeted axillary surgery following neoadjuvant chemotherapy in breast cancer patients

ObjectivesA targeted surgical approach which accurately determines axillary status after neoadjuvant chemotherapy (NAC) may allow appropriate de-escalation of surgical treatment. It is postulated that the combined use of a particular marker clip, ULTRACOR®TWIRL™ (Bard, Inc.), and specific ultrasound settings for its identification, may overcome the challenges of pre-operative localisation with size diminution of nodes following NAC. Hence, this feasibility study was performed.MethodsThree patients with locally advanced breast cancer (LABC), who had the Twirl marker clip placed in biopsy-proven metastatic axillary lymph nodes and completed treatment were included in this preliminary study. Preoperative sonographic identification of the clip and associated node was done on the day of surgery, confirmed by eliciting the ‘twinkle’ artifact, followed by hookwire localisation and resection. The ‘twinkle’ artifact was demonstrated within each specimen after resection.ResultsAll three patients who completed treatment for LABC had successful identification and resection of clipped node aided by the ‘twinkle artifact’.ConclusionThe ‘twinkle’ artifact is a novel and useful aid in identifying the Twirl™ clip marking a lymph node in the post-NAC setting, with the potential to be used intraoperatively.     

Does the pretreatment tumor sampling location correspond with metabolic activity on 18F-FDG PET/CT in breast cancer patients scheduled for neoadjuvant chemotherapy?

Purpose

To define the correlation between the core biopsy location and the area with highest metabolic activity on 18F-FDG PET/CT in stage II–III breast cancer patients before neoadjuvant chemotherapy. Also, we would like to select a subgroup of patients in which PET/CT information may optimize tumor sampling.

Methods

A PET/CT in prone position was acquired in 199 patients with 203 tumors. The distance and relative difference in standardized uptake value (SUV) between core biopsy localization (indicated by a marker) and area with highest degree of FDG uptake were evaluated. A distance ≥2 cm and a relative difference in SUV ≥25% were considered clinically relevant and a combination of both was defined as non-correspondence. Non-correspondence for different tumor characteristics (TNM stage, lesion morphology on MRI and PET/CT, histology, subtype, grade, and Ki-67) was assessed.

Results

Non-correspondence was found in 28 (14%) of 203 tumors. Non-correspondence was significantly associated with T-stage, lesion morphology on MRI and PET/CT, tumor diameter, and histologic type. It was more often seen in tumors with a higher T-stage (p = 0.028), diffuse (non-mass) and multifocal tumors on MRI (p = 0.001), diffuse and multifocal tumors on PET/CT (p < 0.001), tumors >3 cm (p < 0.001), and lobular carcinomas (p < 0.001). No association was found with other features.

Conclusion

Non-correspondence between the core biopsy location and area with highest FDG uptake is regularly seen in stage II–III breast cancer patients. PET/CT information and possibly FDG-guided biopsies are most likely to improve pretreatment tumor sampling in tumors >3 cm, lobular carcinomas, and diffuse and multifocal tumors.     

Occurrence of pneumonitis following radiotherapy of breast cancer – A prospective study

Aim

of this study is to determine the temporal resolution of therapy-induced pneumonitis, and to assess promoting factors in adjuvant treated patients with unilateral mammacarcinoma.

Patients and methods

A total of 100 post-surgery patients were recruited. The cohort was treated by 2 field radiotherapy (2FRT; breast and chest wall, N?=?75), 3 field radiotherapy (3FRT; + supraclavicular lymphatic region, N?=?8), or with 4 field radiotherapy (4FRT; + parasternal lymphatic region, N?=?17). Ninety-one patients received various systemic treatments prior to irradiation. Following an initial screening visit post-RT, two additional visits after 12 and 25 weeks were conducted including radiographic examination. In addition, general anamnesis and the co-medication were recorded. The endpoint was reached as soon as a pneumonitis was developed or at maximum of six months post-treatment.

Results

A pneumonitis incidence of 13% was determined. Of 91 patients with prior systemic therapy, 11 patients developed pneumonitis. Smoking history and chronic obstructive pulmonary disease (COPD) appeared to be positive predictors, whereas past pneumonia clearly promoted pneumonitis. Further pneumonitis-promoting predictors are represented by the applied field extensions (2 field radiotherapy [2FRT]?<?3 field radiotherapy [3FRT]?<?4 field radiotherapy [4FRT]) and the type of combined initial systemic therapies. As a consequence, all of the three patients in the study cohort treated with 4FRT and initial chemotherapy combined with anti-hormone and antibody protocols developed pneumonitis. A combination of the hormone antagonists tamoxifen and goserelin might enhance the risk for pneumonitis. Remarkably, none of the 11 patients co-medicated with statins suffered from pneumonitis.

Conclusions

The rapidly increasing use of novel systemic therapy schedules combined with radiotherapy (RT) needs more prospective studies with larger cohorts. Our results indicate that contribution to pneumonitis occurrence of various (neo)adjuvant therapy approaches followed by RT is of minor relevance, whereas mean total lung doses of >10 Gy escalate the risk of lung tissue complications. The validity of potential inhibitors of therapy-induced pneumonitis as observed for statin co-medication should further be investigated in future trials.

     

Computed tomographic peritoneography prior to intraperitoneal chemotherapy in advanced müllerian cancer: a pilot study

ObjectiveThe objective of this study was to utilize computed tomographic peritoneography (CTP) to assess distribution prior to intraperitoneal chemotherapy for advanced müllerian cancer.MethodsNineteen patients were submitted to CTP. A novel 6-point peritoneal distribution index was developed and applied to the patients prospectively.ResultsThe median peritoneal distribution index was 6 (range, 4–6). The most common region for incomplete peritoneal distribution correlated to the right subphrenic space.ConclusionFurther studies are needed to determine the impact of inadequate distribution on recurrence and survival.     

Prognostic relevance at 5 years of the early monitoring of neoadjuvant chemotherapy using 18F-FDG PET in luminal HER2-negative breast cancer

Purpose

The objective of this study was to evaluate, in the luminal human epidermal growth factor receptor 2 (HER2)-negative breast cancer subtype, the prognostic value of tumour glucose metabolism at baseline and of its early changes during neoadjuvant chemotherapy (NAC).

Methods

This prospective study included 61 women with hormone-sensitive HER2-negative breast cancer treated with NAC. ¹⁸F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed at baseline. Hepatic activity was used as a reference to distinguish between low metabolic and hypermetabolic tumours. In hypermetabolic tumours, a PET exam was repeated after the first course of NAC. The relative change in the maximum standardized uptake value of the tumour (?SUV) was calculated.

Results

Nineteen women had low metabolic luminal breast cancers at baseline, correlated with low proliferation indexes. Forty-two women had hypermetabolic tumours, corresponding to more proliferative breast cancers with higher Ki-67 expression (p?=?0.017) and higher grade (p?=?0.04). The median follow-up period was 64.2 months (range 11.5–93.2). Thirteen women developed recurrent disease, nine of whom died. Worse overall survival was associated with larger tumour size [>5 cm, hazard ratio (HR)?=?6.52, p?=?0.009] and with hypermetabolic tumours achieving a low metabolic response after one cycle of NAC (ΔSUV?<?16 %, HR?=?10.63, p?=?0.004). Five-year overall survival in these poor responder patients was 49.2 %. Overall survival in women with low metabolic tumours or hypermetabolic/good response tumours was 100 and 96.15 %, respectively.

Conclusion

In luminal HER2-negative breast tumours, tumour metabolism at baseline and changes after the first course of NAC are early surrogate markers of patients’ survival. A subgroup of women with hypermetabolic/poorly responding tumours, correlated with poor prognosis at 5 years, can be identified early. These results may guide future studies by tailoring the NAC regimen to the metabolic response.     

Interim heterogeneity changes measured using entropy texture features on T2-weighted MRI at 3.0 T are associated with pathological response to neoadjuvant chemotherapy in primary breast cancer

Objectives

To investigate whether interim changes in hetereogeneity (measured using entropy features) on MRI were associated with pathological residual cancer burden (RCB) at final surgery in patients receiving neoadjuvant chemotherapy (NAC) for primary breast cancer.

Methods

This was a retrospective study of 88 consenting women (age: 30–79 years). Scanning was performed on a 3.0 T MRI scanner prior to NAC (baseline) and after 2–3 cycles of treatment (interim). Entropy was derived from the grey-level co-occurrence matrix, on slice-matched baseline/interim T2-weighted images. Response, assessed using RCB score on surgically resected specimens, was compared statistically with entropy/heterogeneity changes and ROC analysis performed. Association of pCR within each tumour immunophenotype was evaluated.

Results

Mean entropy percent differences between examinations, by response category, were: pCR: 32.8%, RCB-I: 10.5%, RCB-II: 9.7% and RCB-III: 3.0%. Association of ultimate pCR with coarse entropy changes between baseline/interim MRI across all lesions yielded 85.2% accuracy (area under ROC curve: 0.845). Excellent sensitivity/specificity was obtained for pCR prediction within each immunophenotype: ER+: 100%/100%; HER2+: 83.3%/95.7%, TNBC: 87.5%/80.0%.

Conclusions

Lesion T2 heterogeneity changes are associated with response to NAC using RCB scores, particularly for pCR, and can be useful across all immunophenotypes with good diagnostic accuracy.

Key Points

? Texture analysis provides a means of measuring lesion heterogeneity on MRI images.? Heterogeneity changes between baseline/interim MRI can be linked with ultimate pathological response.? Heterogeneity changes give good diagnostic accuracy of pCR response across all immunophenotypes.? Percentage reduction in heterogeneity is associated with pCR with good accuracy and NPV.

     

Staying abreast of imaging – Current status of breast cancer detection in high density breast

ObjectivesThe aim of this paper is to illustrate the current status of imaging in high breast density as we enter a new decade of advancing medicine and technology to diagnose breast lesions.Key findingsEarly detection of breast cancer has become the chief focus of research from governments to individuals. However, with varying breast densities across the globe, the explosion of breast density information related to imaging, phenotypes, diet, computer aided diagnosis and artificial intelligence has witnessed a dramatic shift in new screening recommendations in mammography, physical examination, screening younger women and women with comorbid conditions, screening women at high risk, and new screening technologies. Breast density is well known to be a risk factor in patients with suspected/known breast neoplasia. Extensive research in the field of qualitative and quantitative analysis on different tissue characteristics of the breast has rapidly become the chief focus of breast imaging. A summary of the available guidelines and modalities of breast imaging, as well as new emerging techniques under study that can potentially provide an augmentation or even a replacement of those currently available.ConclusionDespite all the advances in technology and all the research directed towards breast cancer, detection of breast cancer in dense breasts remains a dilemma.Implications for practiceIt is of utmost importance to develop highly sensitive screening modalities for early detection of breast cancer.     

Influence of additional breast ultrasound on cancer detection in a cohort study for quality assurance in breast diagnosis—analysis of 102,577 diagnostic procedures

Purpose  

To determine the value of a breast ultrasound (US) examination in addition to mammography in cases of American College of Radiology (ACR) tissue pattern III and IV in symptomatic women and women at risk.     

The use of 3′-deoxy-3′-18F-fluorothymidine (FLT) PET in the assessment of long-term survival in breast cancer patients treated with neoadjuvant chemotherapy

Annals of Nuclear Medicine - To assess the role of serial FLT-PET scans during early neoadjuvant treatment as a prognostic marker of response to treatment and survival. This study is a prospective...     

Out of balance – Postural control in cancer patients before and after neurotoxic chemotherapy

BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect deriving from neurotoxic chemotherapeutic agents. The underlying nerve injury can affect proprioception causing impaired postural control, gait difficulties and a higher risk of falling. Overall, the symptoms and functional limitations negatively affect patients’ independence and quality of life.Research questionOur objective was to analyze postural control in cancer patients before and after neurotoxic chemotherapy and to compare these data to healthy controls.MethodsParticipants were 35 cancer patients (PAT) and 35 healthy, one-to-one gender, age, height, and weight matched controls (HMC). Postural control of HMC was tested once, whereas PAT were tested prior to (PAT_pre) and three weeks after completion of neurotoxic chemotherapy (PAT_post). Temporal, spatial and frequency domain measures of the center of pressure (COP) were calculated using a force plate. The following balance conditions were analyzed: bipedal stance with open (BP_EO) and closed eyes (BP_EC), semi-tandem (ST_EO, ST_EC) and monopedal stance (MP_EO). CIPN was assessed clinically (Total Neuropathy Score) and via questionnaire. Time and group differences were determined by using Wilcoxon-signed-rank tests. Spearman correlation was applied to analyze associations between severity of CIPN and postural control.ResultsPAT_post showed significantly increased temporal and spatial measures of the COP (p < .05) – both after neurotoxic chemotherapy (PAT_pre–PAT_post) and in comparison to HMC. Withdrawal of visual control resulted in greater temporal and spatial COP displacements in PAT_post than in the comparative groups (PAT_pre, HMC). Correlation analyzes revealed moderate associations of COP measures with clinical CIPN measures and low to none for the questionnaires.SignificanceThree weeks after completion of neurotoxic chemotherapy, PAT_post showed significant balance deficits compared to PAT_pre and HMC. Especially the deficits in the standing conditions with closed eyes may indicate an impaired proprioception. This hypothesis is supported by the finding that stronger CIPN symptoms were associated with poorer postural control. However, future studies need to take further influencing factors on postural control into account (e.g. strength) in order to generate efficacious rehabilitation measures.