The use of bioimpedance spectroscopy to monitor response to treatment interventions with breast cancer-related lymphedema.

2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 138-138
Author(s):  
Chirag Shah ◽  
Frank Vicini ◽  
Peter D. Beitsch ◽  
Beth Anglin ◽  
Alison Lisa Laidley ◽  
...  

138 Background: Currently, limited tools are available to assess response to therapy in patients with breast cancer related lymphedema (BCRL). The purpose of this study was to perform an exploratory analysis to determine if, in clinical settings, bioimpedance spectroscopy (BIS) can detect changes in extracellular fluid volume in response to treatment of BCRL. Methods: Three centers that had experience with BIS (L-Dex U400, ImpediMed Limited, Brisbane, Australia) provided retrospective data on 50 patients with breast cancer who were evaluated with BIS at baseline and following loco-regional procedures. Patients had a pre-surgical L-Dex measurement as well as at least 2 post-surgical measurements (before and after BCRL intervention). Decisions regarding intervention were made by physicians with no L-Dex score cut-off utilized. An analysis was performed comparing changes in L-Dex scores for those patients undergoing treatment for BCRL (n=13) versus those not undergoing intervention (n=37). A second analysis was also performed on all patients with elevated L-Dex scores compared to baseline prior to intervention (n=32). Results: The mean age was 54 years old. Fifty four percent of patients underwent SLN biopsy with a mean of 7.9 nodes removed. The mean change in L-Dex score from baseline (pre-treatment) to the first post-surgical L-Dex score measurement was 3.3 +/- 6.8. When comparing the cohort treated for BCRL to those not treated, L-Dex scores were significantly reduced (-4.3 v. 0.1, p=0.005) following intervention. For the subset of patients with elevated L-Dex scores post-surgery, the change in L-Dex score following BCRL intervention was significantly reduced (-5.8 v. 0.1, p=0.001) compared with those observed. Conclusions: These results confirm that BIS can detect increases in L-Dex scores following breast surgery and can also detect reductions in L-Dex scores following intervention for early onset lymphedema. These results demonstrate that BIS has significant clinical utility as it can be used to monitor patients with early BCRL who undergo intervention and to follow these patients (through serial measurements) to document their short and long-term response to these treatments.

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 89-89
Author(s):  
Frank Vicini ◽  
Douglas W. Arthur ◽  
Maureen Lyden ◽  
Chirag Shah

89 Background: The purpose of the study was to evaluate bioelectrical impedance spectroscopy's (BIS) ability to detect and monitor extracellular fluid accumulation of the upper limb as it relates to the extent of locoregional therapy for patients with breast cancer. Methods: A total of 125 patients from 4 clinical practices, with newly diagnosed breast cancer were evaluated at baseline and following locoregional procedures that could potentially affect fluid accumulation in the arm and signal the possible development of early lymphedema. In order to assess the ability of BIS to detect sub-clinical changes by treatment modality, the change in L-Dex score from baseline to measurements taken within 180 days following surgery were calculated. Results: Fifty-one patients (40.8%) underwent lumpectomy and 74 (59.2%) mastectomy; 68 patients (54.4%) underwent sentinel lymph node (SLN) sampling. Sixty-five patients underwent radiation therapy (RT) with RT patients being more likely to have undergone lumpectomy (66.2% v. 3.2%, p<0.001) and axillary dissection (41.5% v. 19.4%, p=0.04) compared with patients not receiving RT. However, no difference in the mean number of nodes sampled (7.7 v. 5.4, p=0.14) was noted for patients receiving RT compared with those not receiving RT. Patients receiving RT had a significantly increased change in L-Dex score (0.8 v. -2.5, p=0.03) compared with those patients not receiving RT. For all patients, ALND was associated with a significantly increased change in L-Dex score (5.0 v. 0.3, p=0.003) compared with SLN. When stratifying by the number of nodes removed, a statistically significant increase in the change in L-Dex score was noted (0.4 v. 0.4 v. 4.3 v. 6.4, p=0.04) for 0-3, 4-6, 7-10, and greater than 10 lymph nodes removed. Conclusions: In this limited analysis, L-Dex scores paralleled the extent of axillary sampling and the addition of radiation therapy; these results suggest that BIS can be used to monitor patients for the early onset of edema as differences emerged within 180 days of surgery.


2015 ◽  
Vol 112 (46) ◽  
pp. 14325-14330 ◽  
Author(s):  
Sara M. Tolaney ◽  
Yves Boucher ◽  
Dan G. Duda ◽  
John D. Martin ◽  
Giorgio Seano ◽  
...  

Preoperative bevacizumab and chemotherapy may benefit a subset of breast cancer (BC) patients. To explore potential mechanisms of this benefit, we conducted a phase II study of neoadjuvant bevacizumab (single dose) followed by combined bevacizumab and adriamycin/cyclophosphamide/paclitaxel chemotherapy in HER2-negative BC. The regimen was well-tolerated and showed a higher rate of pathologic complete response (pCR) in triple-negative (TN)BC (11/21 patients or 52%, [95% confidence interval (CI): 30,74]) than in hormone receptor-positive (HR)BC [5/78 patients or 6% (95%CI: 2,14)]. Within the HRBCs, basal-like subtype was significantly associated with pCR (P= 0.007; Fisher exact test). We assessed interstitial fluid pressure (IFP) and tissue biopsies before and after bevacizumab monotherapy and circulating plasma biomarkers at baseline and before and after combination therapy. Bevacizumab alone lowered IFP, but to a smaller extent than previously observed in other tumor types. Pathologic response to therapy correlated with sVEGFR1 postbevacizumab alone in TNBC (Spearman correlation 0.610,P= 0.0033) and pretreatment microvascular density (MVD) in all patients (Spearman correlation 0.465,P= 0.0005). Moreover, increased pericyte-covered MVD, a marker of extent of vascular normalization, after bevacizumab monotherapy was associated with improved pathologic response to treatment, especially in patients with a high pretreatment MVD. These data suggest that bevacizumab prunes vessels while normalizing those remaining, and thus is beneficial only when sufficient numbers of vessels are initially present. This study implicates pretreatment MVD as a potential predictive biomarker of response to bevacizumab in BC and suggests that new therapies are needed to normalize vessels without pruning.


2021 ◽  
Author(s):  
Marieke A. Helmich ◽  
M. Wichers ◽  
Frenk Peeters ◽  
Evelien Snippe

More instability (MSSD) and variability (SD) of negative affect (NA) have been related to current and future depressive symptoms. We investigated whether MSSD and SD of NA were predictive of the rate of symptom improvement during treatment and of reaching remission status. Forty-six individuals with major depressive disorder completed six days of ecological momentary assessments (10 beeps per day) before starting a combination of pharmacotherapy and supportive therapy. During and after treatment, the Hamilton Depression Rating Scale (HDRS) diagnostic interview was performed monthly for 18 months. Using multilevel modeling and logistic regression, a linear decrease in HDRS scores as well as reaching remission status (HDRS of ≤7 within or after five months) were predicted by the mean, SD and MSSD of NA in momentary assessments, and relevant baseline predictors. Mean NA, but not the SD or MSSD of NA, predicted rates of depressive symptom reduction over five months. The odds of remitting during treatment were not associated with any predictors. Our results suggest that pre-treatment assessments of NA instability and variability may not give an indication of the treatment response over time. Clinically, the mean of NA may be more promising as a baseline indicator of response potential.


2021 ◽  
Author(s):  
Luis E. Raez ◽  
Kathleen Danenberg ◽  
Daniel Sumarriva ◽  
Joshua Usher ◽  
Jacob Sands ◽  
...  

Aim: We report an exploratory analysis of cfRNA as a biomarker to monitor clinical responses in non-small cell lung cancer (NSCLC), breast cancer, and colorectal cancer (CRC). An analysis of cfRNA as a method for measuring PD-L1 expression with comparison to clinical responses was also performed in the NSCLC cohort. Methods: Blood samples were collected from 127 patients with metastatic disease that were undergoing therapy, 52 with NSCLC, 50 with breast cancer, and 25 with CRC. cfRNA was purified from fractionated plasma, and following reverse transcription (RT), total cfRNA and gene expression of PD-L1were analyzed by real-time polymerase chain reaction (qPCR) using beta-actin expression as a surrogate for relative amounts of cfDNA and cfRNA. For the concordance study of liquid biopsies and tissue biopsies, the isolated RNA was analyzed by RNAseq for the expressions of 13 genes. We had to close the study early due to a lack of follow-up during the Covid-19 pandemic. Results: We collected a total of 373 blood samples. Mean cfRNA PCR signals after RT were about 50-fold higher than those of cfDNA. cfRNA was detected in all patients, while cfDNA was detected in 88% of them. A high concordance was found for the expression levels of 13 genes between blood and solid tumor tissue. Changes in cfRNA levels followed over the course of treatments were associated with response to therapy, increasing in progressive disease (PD) and falling when a partial response (PR) occurred. The expression of PD-L1 over time in patients treated with immunotherapy decreased with PR but increased with PD. Pre-treatment levels of PD-L1 were predictive of response in patients treated with immunotherapy. Conclusion: Changes in cfRNA correlate with clinical response to the therapy. Total cfRNA may be useful in predicting clinical outcomes. PD-L1 gene expression may provide a biomarker to predict response to PD-L1 inhibition.


2020 ◽  
pp. 112067212096345
Author(s):  
Marco Lupidi ◽  
Ramkailash Gujar ◽  
Alessio Cerquaglia ◽  
Jay Chhablani ◽  
Daniela Fruttini ◽  
...  

Purpose: To quantitatively assess retinal neovascularizations (RNVs) in proliferative diabetic retinopathy (PDR) before and after photocoagulative laser treatment (PLT) using Optical Coherence Tomography Angiography (OCT-A). Methods: Consecutive patients with PDR were examined with fluorescein angiography (FA) and OCT-A before and after PLT. Baseline and after-treatment FA images were quantitatively analyzed to assess both the RNVs area and leakage area. On OCT-A RNVs area, vascular perfusion density (VPD), vessel length density (VLD) and fractal dimension were computed. VPD of the full-retina OCT-A underneath the RNV was determined to evaluate potential laser-induced changes in vascular perfusion. Results: Fifteen eyes of 13 patients with PDR were enrolled. The mean area of the RNVs was 0.47 ± 0.50 mm2 in the baseline OCT-A and 0.32 ± 0.40 mm2 in the post-treatment assessment ( p = 0.0002). The mean RNV VPD of RNV was 2% ± 4% in pre-treatment and 1% ± 1% for the post-treatment ( p = 0.0001). The mean VLD of RNV was 7.26 ± 1.53 at baseline and 6.64 ± 1.65 in the post treatment ( p = 0.0002). A significant difference in terms of mean RNVs area and VPD reduction between eyes that needed additional treatment and those that did not (~40% vs ~20%; p < 0.05), was observed. Mean VPD of full-retinal thickness OCT-angiogram was 55% ± 10% for the pre-treatment and 53% ± 8% for the post treatment scan ( p = 0.02). Conclusion: The quantitative OCT-A assessment of laser-induced changes of RNVs can be a useful non-invasive approach for determining treatment efficacy. A reduction of RNVs area or VPD ⩾ 40% might reveal those eyes that won’t require additional treatment. Retinal perfusion impairment seemed to progress independently from the treatment.


Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2918
Author(s):  
Simone Borgoni ◽  
Emre Sofyalı ◽  
Maryam Soleimani ◽  
Heike Wilhelm ◽  
Karin Müller-Decker ◽  
...  

Breast cancer is one of the leading causes of death for women worldwide. Patients whose tumors express Estrogen Receptor α account for around 70% of cases and are mostly treated with targeted endocrine therapy. However, depending on the degree of severity of the disease at diagnosis, 10 to 40% of these tumors eventually relapse due to resistance development. Even though recent novel approaches as the combination with CDK4/6 inhibitors increased the overall survival of relapsing patients, this remains relatively short and there is a urgent need to find alternative targetable pathways. In this study we profiled the early phases of the resistance development process to uncover drivers of this phenomenon. Time-resolved analysis revealed that ATF3, a member of the ATF/CREB family of transcription factors, acts as a novel regulator of the response to therapy via rewiring of central signaling processes towards the adaptation to endocrine treatment. ATF3 was found to be essential in controlling crucial processes such as proliferation, cell cycle, and apoptosis during the early response to treatment through the regulation of MAPK/AKT signaling pathways. Its essential role was confirmed in vivo in a mouse model, and elevated expression of ATF3 was verified in patient datasets, adding clinical relevance to our findings. This study proposes ATF3 as a novel mediator of endocrine resistance development in breast cancer and elucidates its role in the regulation of downstream pathways activities.


1976 ◽  
Vol 83 (4) ◽  
pp. 856-864 ◽  
Author(s):  
Pentti Holma ◽  
Herman Adlercreutz

ABSTRACT Plasma levels of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) as well as the response of LH and FSH to the intravenous administration of 100 μg of luteinizing hormone releasing hormone (LRH) were measured in 16 well-trained athletes (mean age 30 years) before and after 2 months of daily oral intake of 15 mg of metandienon, an anabolic steroid (Anabolin®, 17α-methyl-17β-hydroxy-1,4-androstadien-3-one, Medica, Finland). All athletes continued to train regularly, just as they had done for several years. During administration of metandienon the mean plasma testosterone level fell 69%, from 29.4 ± 11.6 nmol/l to 9.1 ± 7.5 nmol/l. The mean plasma levels of LH and FSH also fell significantly (P < 0.001 and P < 0.01, respectively), both about 50%. Because LH and FSH levels were low after administration of the steroid the maximum stimulation values after LRH administration were also lower than pre-treatment values although the mean increments did not differ significantly before and after administration of the anabolic steroid. However, after treatment, the FSH response curve had a biphasic pattern in most subjects, with peaks at 10 to 20 and 50 to 60 min after the iv injection of LRH. Administration of LRH after the treatment period had no effect on FSH secretion in two subjects and no effect on LH secretion in one. Our results show that administration of an anabolic steroid causes a pronounced lowering of plasma levels of testosterone, LH and FSH but causes no gross alteration in the response of LH secretion to stimulation by LRH. The reason for the biphasic response pattern of FSH to LRH administration in most subjects is not known.


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