Veronica Mariotti

A novel model of dormancy for bone metastatic breast cancer cells

Mortality of patients with breast cancer is due overwhelmingly to metastatic spread of the disease. Although dissemination is an early event in breast cancer, extended periods of cancer cell dormancy can result in long latency of metastasis development. Deciphering the mechanisms underlying cancer cell dormancy and subsequent growth at the metastatic site would facilitate development of strategies to interfere with these processes. A challenge in this undertaking has been the lack of models for cancer cell dormancy. We have established novel experimental systems that model the bone microenvironment of the breast cancer metastatic niche. These systems are based on 3D cocultures of breast cancer cells with cell types predominant in bone marrow. We identified conditions in which cancer cells are dormant and conditions in which they proliferate. Dormant cancer cells were able to proliferate upon transfer into supportive microenvironment or upon manipulation of signaling pathways that control dormancy. These experimental systems will be instrumental for metastasis studies, particularly the study of cellular dormancy.

Mesenchymal stromal/stem cells in drug therapy: New perspective.

Mesenchymal stromal/stem cells (MSC) have emerged as a class of cells suitable for cellular delivery of nanoparticles, drugs and micro-RNA cargo for targeted treatments such as tumor and other protective mechanisms. The special properties of MSC underscore the current use for various clinical applications. Examples of applications include but are not limited to regenerative medicine, immune disorders and anti-cancer therapies. In recent years, there has been intense research in modifying MSC to achieve targeted and efficient clinical outcomes. This review discusses effects of MSC in an inflammatory microenvironment and then explains how these properties could be important to the overall application of MSC in cell therapy. The article also advises caution in the application of these cells because of their role in tumorigenesis. The review stresses the use of MSC as vehicles for drug delivery and discusses the accompanying challenges, based on the influence of the microenvironment on MSC.

Assessing fracture risk in early stage breast cancer patients treated with aromatase-inhibitors: An enhanced screening approach incorporating trabecular bone score

Introduction Aromatase-inhibitors (AIs) are commonly used for treatment of patients with hormone-receptor positive breast carcinoma, and are known to induce bone density loss and increase the risk of fractures. The current standard-of-care screening tool for fracture risk is bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). The fracture risk assessment tool (FRAX®) may be used in conjunction with BMD to identify additional osteopenic patients at risk of fracture who may benefit from a bone-modifying agent (BMA). The trabecular bone score (TBS), a novel method of measuring bone microarchitecture by DXA, has been shown to be an independent indicator of increased fracture risk. We report how the addition of TBS and FRAX®, respectively, to BMD contribute to identification of elevated fracture risk (EFR) in postmenopausal breast cancer patients treated with AIs. Methods 100 patients with early stage hormone-positive breast cancer treated with AIs, no prior BMAs, and with serial DXAs were identified. BMD and TBS were measured from DXA images before and following initiation of AIs, and FRAX® scores were calculated from review of clinical records. EFR was defined as either: BMD ≤−2.5 or BMD between −2.5 and −1 plus either increased risk by FRAX® or degraded microstructure by TBS. Results At baseline, BMD alone identified 4% of patients with EFR. The addition of FRAX® increased detection to 13%, whereas the combination of BMD, FRAX® and TBS identified 20% of patients with EFR. Following AIs, changes in TBS were independent of changes in BMD. On follow-up DXA, BMD alone detected an additional 1 patient at EFR (1%), whereas BMD+ FRAX® identified 3 additional patients (3%), and BMD+FRAX®+TBS identified 7 additional patients (7%). Conclusions The combination of FRAX®, TBS, and BMD maximized the identification of patients with EFR. TBS is a novel assessment that enhances the detection of patients who may benefit from BMAs.

Stem cell in alternative treatments for brain tumors: potential for gene delivery

Despite ongoing research efforts and attempts to bring new drugs into trial, the prognosis for brain tumors remains poor. Patients with the most common and lethal intracranial neoplasia, glioblastoma multiforme (GBM), have an average survival of one year with combination of surgical resection, radiotherapy and temozolomide. One of the main problems in the treatment of GBM is getting drugs across the blood brain barrier (BBB) efficiently. In an attempt to solve this problem, there are ongoing experimental and clinical trials to deliver drugs within stem cells. The purpose for this method is the ease by which stem cells home to the brain. This review discusses the experimental and clinical applications of stem cells for GBM. We also discuss the different properties of stem cells. This information is important to understand why one stem cell would be advantageous over another in cell therapy. We provide an overview of the different drug delivery methods, gene-based treatments and cancer vaccines for GBM, including the stem cell subset.

In-Hospital Mortality and Post-Transplantation Complications in Elderly Multiple Myeloma Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation: A Population-Based Study

Autologous hematopoietic stem cell transplantation (auto-HSCT) has improved survival in patients with multiple myeloma (MM) and is increasingly used in elderly patients. The aim of this study was to characterize and compare in-hospital complications and mortality after auto-HSCT in younger (< age 65) versus elderly (> age 65) MM patients utilizing the Nationwide Inpatient Sample. Over a 3-year period (2008 to 2010), 2209 patients with MM were admitted to US hospitals for auto-HSCT. The median age was 59 years, with 1650 patients (74.7%) younger than age 65 and 559 patients (25.3%) 65 or older. Overall, in-hospital mortality in MM patients after auto-HSCT was rare (1.5%) and there was no significant difference in mortality between elderly and younger patients. Elderly patients did have a significantly increased mean length of stay (18.6 days + 10.8 days [SD] versus 16.8 days + 7.2 days [SD], P < .001) and mean total hospital charges (

Abstract A27: Diversity in multiple myeloma clinical trials

161,117 + 

Post-gastrectomy complications and mortality in elderly patients with gastric cancer: A population-based study.

105,008 [SD] versus

Too sick to enroll? Comorbidities limiting recruitment in early phase trials, review of over 1,100 clinical trials.

151,192 + 

P2.01-054 Inclusion of Central Nervous System Metastasis in Lung Cancer Early Phase Clinical Trials

78,342 [SD] , P = .018) compared with younger patients. Elderly patients were significantly more likely than younger patients to develop major in-hospital post-transplantation complications such as severe sepsis (odds ratio [OR], 2.70; 95% confidence interval [CI], 1.40 to 5.21; P = .003), septic shock (OR, 3.10; 95% CI, 1.43 to 6.71; P = .004), pneumonia (OR, 1.62; 95% CI, 1.06 to 2.46; P = .024), acute respiratory failure (OR, 3.44; 95% CI, 1.70 to 6.96; P = .001), endotracheal intubation requiring prolonged mechanical ventilation (OR, 2.19; 95% CI, 1.06 to 4.55; P = .035), acute renal failure (OR, 2.14; 95% CI, 1.38 to 3.33; P = .001), and cardiac arrhythmias (OR, 2.06; 95% CI, 1.52 to 2.79; P <.001). These data may help guide informed consent discussions and provide a focus for future studies to reduce treatment-related morbidity in elderly MM patients undergoing auto-HSCT.

Evolution of pancreatic cancer survival over the past two decades.

Background: Multiple myeloma (MM) accounts for approximately 1% of all cancers and 10% of hematologic malignancies in the United States (U.S.). MM occurs in all races, but the incidence in African Americans is two to three times higher than in non-Hispanic whites. MM is also slightly more frequent in men than women (1.4:1). Many clinical trials lack appropriate representation of specific patient populations, limiting the generalizability of the evidence obtained. Therefore, we determined the representation of ethnic minorities, the elderly, and women in MM clinical trials. Methods: Enrollment data from all therapeutic trials reported as completed in clinicaltrial.gov from 2000 to 2016 were analyzed. Clinical trials including other hematologic malignancies and with recruitment outside of the U.S. were excluded. Enrollment fraction (EF) was defined as the number of enrollees divided by the 2013 SEER database MM complete prevalence. Chi-square test was used to estimate differences in categorical data. Results: Out of 177 MM clinical trials (CT), 78 (44%) reported ethnicity with a total of 12,055 enrollees. Regarding enrollees9 ethnic composition, 84% were non-Hispanic White (NHW), 8.6% African American (AA), 2.8% Asian, 1.8% Hispanic, and 0.1% Native American/Alaskan Indian. Out of those 78 CT, 52 (66%) were phase II, 15 (19%) phase III, and 11 (14%) phase I. Most of the results were published from 2012 to 2016 (74%). Forty-six (59%) trials were sponsored by industry, 7 (9%) by NCI, and 25 (32%) were investigator initiated. Participation in CT varied significantly across ethnic groups, NHW were more likely to be enrolled in CT (EF of 0.23) than AA (EF of 0.08, p Conclusions: Despite the higher incidence of MM in African Americans and the elderly, the former only represented 8.6% of the study participants and 66% of these were less than 65 years of age; therefore, we are lacking data in the tolerability of these new agents in our aging MM population. We also observed that industry studies were less likely to recruit AA patients. Collaborations between investigators, sponsors, and the community are necessary to increase our minority and elderly patients9 access to clinical trials. Citation Format: Narjust Duma, Miguel Gonzalez Velez, Jesus Vera-Aguilera, Richardo Parrondo, Veronica Mariotti, Jonas Paludo, Yucai Wang, Ronald Go, Alex Adjei. Diversity in multiple myeloma clinical trials [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr A27.