Abstract Background Our study aim was to evaluate neuromuscular ultrasound (NMUS) for the assessment of taxane chemotherapy‐induced peripheral neuropathy (CIPN), the dose‐limiting toxicity of this agent. Methods This cross‐sectional study of breast cancer patients with taxane CIPN measured nerve cross‐sectional area (CSA) by NMUS and compared with healthy historical controls. Correlations were determined between CSA and symptom scale, nerve conduction studies, and intraepidermal nerve fiber density (IENFD). Results A total of 20 participants reported moderate CIPN symptoms at a median of 3.8 months following the last taxane dose. Sural nerve CSA was 1.2 mm 2 smaller than healthy controls ( P ≤ .01). Older age and time since taxane were associated with smaller sural nerve CSA. For each 1 mm 2 decrease in sural nerve CSA, distal IENFD decreased by 2.1 nerve/mm (R 2 0.30; P = .04). Conclusions These data support a sensory predominant taxane neuropathy or neuronopathy and warrant future research on longitudinal NMUS assessment of CIPN.
Abstract Background Premenopausal women with high-risk hormone receptor (HR)-positive breast cancer often receive ovarian function suppression (OFS) with aromatase inhibitor therapy; however, abrupt menopause induction, together with further decrements in estrogen exposure through aromatase inhibition, may affect cardiovascular microcirculatory function. We examined adenosine-induced changes in left ventricular (LV) myocardial T1, a potential subclinical marker of LV microcirculatory function in premenopausal women undergoing treatment for breast cancer. Methods Twenty-one premenopausal women (14 with HR-positive breast cancer receiving OFS with an aromatase inhibitor and 7 comparator women with triple-negative breast cancer [TNBC] who had completed primary systemic therapy) underwent serial resting and adenosine cardiovascular magnetic resonance imaging measurements of LV myocardial T1 and LV volumes, mass, and ejection fraction. All statistical tests were 2-sided. Results After a median of 4.0 months (range = 3.1-5.7 months), the stress to resting ratio of LV myocardial T1 declined in women with HR-positive breast cancer (−1.3%, 95% confidence interval [CI] = −3.4% to 0.7%) relative to those with TNBC (3.2%, 95% CI = −1.2% to 7.6%, P = .02). After accounting for age, LV stroke volume, LV ejection fraction, diastolic blood pressure, and breast cancer subtype women with HR-positive breast cancer experienced a blunted T1 response after adenosine relative to women with TNBC (difference = −4.7%, 95% CI = −7.3% to −2.1%, Pdifference = .002). Conclusions Over the brief interval examined, women with HR-positive breast cancer receiving OFS with an aromatase inhibitor experienced reductions in adenosine-associated changes in LV myocardial T1 relative to women who received nonhormonal therapy for TNBC. These findings suggest a possible adverse impact on LV myocardial microcirculatory function in premenopausal women with breast cancer receiving hormone deprivation therapy.
This study evaluates the predictive value of post-therapy 18-fluoro-deoxyglucose positron emission tomography (FDG-PET), including indeterminate studies, following curative-intent therapy in diffuse large B-cell lymphoma (DLBCL). Consecutive patients from September 2002 to December 2005 were prospectively offered enrollment in an observational registry. Available FDG-PET reports after primary therapy were interpreted by hematologist–oncologists as positive, negative, or indeterminate. One hundred twenty-five patients with DLBCL had a median follow-up of 35.2 months. Ninety-three percent were treated with R-CHOP-like therapy. Twenty percent of PET reports were judged indeterminate. Event-free survival (EFS) at 3 years for the negative and indeterminate groups was 85% and 71%, respectively (p = 0.28 by log-rank). Overall survival (OS) at 3 years for negative, indeterminate, and positive groups was 89%, 88%, and 48%. Combining the pre-therapy International Prognostic Index (IPI) with the post-therapy FDG-PET result added to the predictive value of the study for patients. Three-year EFS for patients with low or low-intermediate IPI risk and an indeterminate FDG-PET report was 93%, while for those with high or high-intermediate pre-therapy IPI the 3-year EFS was 45% (p < 0.02). Interpreting FDG-PET reports following curative-intent chemotherapy in patients is informative but imprecise, and incorporation of pre-therapy prognosis can improve predictive utility.
Abstract Purpose: The implementation of the innovative technologies remains the top priority for the development of potential modalities for the diagnosis and treatment of various cancers. Despite all the recent advances, ovarian cancer is considered as a lethal gynecologic malignancy in which vast majority of the cases are diagnosed at the late metastatic stage at which the prognosis is poor. Because of the few apparent early symptoms, significant effort was made for developing efficient methods to identify early progression of the disease. We demonstrated that the bioconjugation of the V7 peptide on 27nm wormhole mesoporous silica nanoparticles (V7-CWMSN) particles specifically release the IR780 imaging probe at the orthotopically implanted early-stage ovarian tumor to detect by multispectral optoacoustic imaging technology (MSOT). Methods: Wormhole mesoporous silica nanoparticles (WMSN) were synthesized by sol-gel chemistry. The WMSN were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The surface of the WMSN particle was functionalized with pH sensitizer chitosan to obtain CWMSN. The CWMSN particle was loaded with propidium Iodide (PI) or IR780 infrared imaging dye. Further, the conjugation of the CWMSN with V7 pHLIP peptide (V7-CWMSN) developed pH sensitive cargo release from the nanoparticles. Female athymic mice were orthotopically implanted with ES-2 ovarian cancer cells. Following 10 days of orthotopic implantation of the tumor cells, mice were intravenously injected with V7-CWMSN particles containing IR780 dye and were imaged with MSOT. Results: In the current study, we have synthesized the wormhole-shaped mesoporous silica particles (WMSN) with the 27 nm diameter carrying IR780 imaging probes for the detection of early-stage ovarian cancer. The V7 peptide undergoes a conformational change upon contact with the acidic tumor microenvironment. Also, the chitosan crosslinking on the surface of the particles (V7-CWMSN) acts as a gatekeeper that is degradable upon contact with acidic pH tumor to prevent off-target release. As a model for ovarian cancer, we have used athymic mice orthotopically implanted with ovarian cancer cells. This model closely resembles the human ovarian cancer pathophysiology. Our results have demonstrated that the intravenous delivery of V7-CWMSN particles could detect the orthotopically implanted early-stage ovarian tumors (p<0.0001,n=5). Conclusion: The development of the distinct nanoformulations with potent imaging technology enables the visualization of early-stage ovarian tumors. Translating these modalities may allow clinicians to identify early-stage malignancies that are currently undetectable through conventional imaging techniques. Citation Format: Abhilash Samykutty, Molly W. McNally, William E. Grizzle, Akiko Chiba, Alexandra Thomas, Lacey R. McNally. Acidic tumor microenvironment targeted wormhole-shaped mesoporous silica nanoparticles to detect ovarian cancer by multispectral optoacoustic tomography [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4122.
1057 Background: Prior estimates of costs associated with CPM have been limited to single institution studies or simulation-based decision models and have failed to take into account costs associated with breast reconstruction (BR), also correlated with CPM. Our study uses actual charges incurred in a population-based dataset to estimate costs for the initial procedures as well as surgical complications and additional (addl) breast procedures for CPM and UM. Methods: Women receiving immediate CPM or UM in 2008-2010 were identified from SPARCS, the state of New York’s all payer data reporting system for inpatient stays and outpatient encounters. Claims submitted within two years of the primary breast surgery were collected. Surgical complications and addl breast procedures were also identified. Summed charges were transformed to costs following published cost-to-charge ratios. Log-linear models were fitted to estimate costs of CPM and UM, controlling for age, race, year, insurance status, BR, and the interaction between extent of mastectomy and BR. Results: In our final cohort of 13,110 women, 11% received CPM. Median total costs were 46% ($7,521.72) higher for CPM than UM (p < .01). Those with CPM were more likely than UM to experience complications (30% v 21%, p < .01) and have addl breast procedures (80% v 45%, p < .01), and thus higher follow up costs. However, BR was not uniformly distributed by extent of surgery, as 93% of CPM and 46% of UM patients received BR (p < .01). When stratified by BR, rates of complications did not differ by CPM or UM, but were much higher for those who underwent BR than those who did not (31% and 12% respectively, p < .01). Controlling for BR and patient characteristics, costs were similar between CPM and UM in terms of complications (p = .27), addl breast procedures (p = .19), and overall follow up (p = .98). Conclusions: Despite lack of survival benefit, a growing number of average-risk women elect CPM, often with BR. In our cohort, the complications, addl breast procedures, and higher follow up costs associated with CPM were driven by BR. These additional costs associated with BR should be considered when evaluating the benefit-cost ratio of CPM.
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