bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recognizing seromadesis to prevent false-positive PET-CT interpretations.
Authors: Bhatt Geetika , Li Xiao-Feng , Jain Angita , Stephens Matthew , Civelek Ali Cahid 
Published: March 2020

e22084 Background: Seromas are the result of a local inflammatory response to a mechanical injury incurred by tissue aggression either during surgery or the presence of foreign bodies. Unfortunately, the common practice of using of percutaneous or surgical drains, does not decrease the frequency of seroma formation and is associated with an increased risk of infection. Methods: Since first introduced in 1935 for pleurodesis, talcum powder has been used extensively as a simple, effective, and economic procedure for the treatment and prophylaxis of recurrent pleural effusions. It induces a strong fibrotic reaction due to the activation of polymorphonuclear neutrophils, interleukin 8 and fibroblast growth factor. One of the earliest documented uses was by Coons et al., in 1993 utilizing an experimental dog model. In 2006, Saeb-Parsy et al. described its use in recurrent seroma after breast surgery. More recently in 2012, Klima et al. reported that a prophylactic application of subcutaneous talc after axillary dissection in a porcine model safely reduces drain duration and prevents seromas without local or systemic side effects. More recently, it has also been used in superficial soft tissue excisions for melanomas and large metastatic lymphadenopathy excisions. Currently, F-18 FDG PET-CT is widely used in the diagnosis and management of patients with malignancies. However, the imaging tracer F-18 FDG is utilized not only by malignant cells but by infectious, inflammatory cells as well resulting in false ‘positive’ findings. Results: When a patient undergoes pleurodesis using talc, the local inflammatory process is seen as intense increased F18 FDG activity on PET-CT scan. This can be perceived and misinterpreted as initial or recurrent malignant foci or infection. Thus it is imperative that interpreting physicians be aware of the wide range of application of talcum powder to any site with a potential of seroma development. Conclusions: Presence of intense F-18 FDG activity corresponding to somewhat linear irregular area of hyperdensity seen in the CT portion of PET-CT in previous surgical bed should alert the interpreting physician on strong probability of talc induced exuberant inflammatory reaction and associated F-18 FDG activity.
First results of the prospective Neoadjuvant Breast Registry Symphony Trial (NBRST).
Authors: Whitworth Pat W. , Gittleman Mark , Akbari Stephanie , Stork Lisette , De Snoo Femke , Gibson Jessica , Beitsch Peter D. 
Published: March 2020

e22117 Background: Classification into molecular subtypes may be important for the selection of therapy for patients with early breast cancer. Previous analyses had shown that breast cancer subtypes have distinct clinical outcome (Sorlie, PNAS 2001; Esserman, BCRT 2011). The aim of the prospective NBRST study is to measure chemosensitivity as defined by pathological Complete Response (pCR), or endocrine sensitivity as defined by partial response (PR) and metastasis-free survival in molecular subgroups. Methods: The study includes women aged 18–90 with histologically proven breast cancer, who are scheduled to start neo-adjuvant chemotherapy (CT) or neo-adjuvant endocrine therapy (ET), and who provide written informed consent. Additional inclusion criteria include no excision biopsy or axillary dissection, no confirmed distant metastatic disease, and no prior therapy for breast cancer. Treatment is at the discretion of the physician adhering to NCCN approved regimens. 500 Patients will be enrolled. Results: 128 Patients (median age 52, range 22-79), T1-4 N0-3, had definitive surgery and the overall pCR rate was 22%.14 (11%) patients are classified as Luminal A-type (BluePrint Luminal/MammaPrint Low Risk) of whom 11 received neo-adjuvant CT; none of these patients had a pCR. While 3 patients received neo-adjuvant ET and all 3 had a PR. 47 (37%) Patients are classified as Luminal B-type (BluePrint Luminal/MammaPrint High Risk). All but 1 patient received neo-adjuvant CT and 4 (9%) had a pCR. 20 (16%) Patients are classified as BluePrint HER2-type and received neo-adjuvant CT plus Trastuzumab; 8 (40%) had a pCR. 47 (37%) Patients are classified as BluePrint Basal-type and received neo-adjuvant CT; 15 (32%) had a pCR. Of the patients with IHC/FISH HER2+ cancer 13/39 (33%) had a pCR and 6/21 (29%) of the patients with IHC/FISH triple negative breast cancer. Conclusions: We observed differences in pCR to neo-adjuvant treatment in groups stratified by BluePrint and MammaPrint. Patients with Luminal A-type breast cancer have a high response to neo-adjuvant endocrine therapy (100% PR) and no pCR to neo-adjuvant CT. While patients with BluePrint HER2-type and Basal-type breast cancer have a high pCR rate to neo-adjuvant CT. Clinical trial information: NCT01479101.
Dynamics of T-cell infiltration during the course of ovarian cancer: The gradual shift from a Th17 effector cell response to a predominant infiltration by regulatory T cells.
Authors: Partlova Simona , Fialova Anna , Sojka Ludek , Rob Lukas , Bartunkova Jirina , Spisek Radek 
Published: March 2020

e22129 Background: Ovarian cancer is diagnosed in more than 190,000 new patients every year and is known to have the highest mortality rate among gynaecologic cancers. The type of immune cells that are present within the tumor microenvironment can play a crucial role in the survival of patients. However, little is known about the dynamics of the tumor-infiltrating immune cells during disease progression. Methods: We studied the immune cells infiltrating the tumor tissue of ovarian cancer patients at different stages of disease. We analysed the patterns of T lymphocytes in fresh tumor tissue as well as blood samples of 44 newly diagnosed ovarian cancer patients by flow cytometry. To evaluate whether regulatory T cells (Tregs) develop in situ or migrate to tumor tissue, we measured a concentration of chemokine CCL22 in tumor cell culture supernatants. We also determined the expression of CCR4 on circulating as well as tumor-infiltrating Tregs by flow cytometry. Results: The early stages of development of ovarian carcinomas were characterized by a strong Th17 immune response, whereas in stage II patients, recruitment of high numbers of Th1 cells was observed. In disseminated tumors (stage III-IV), we detected a dominant population of Helios+ activated regulatory T cells along with high numbers of macrophages and immature myeloid dendritic cells. Tumor-infiltrating Tregs had markedly lower expression of CCR4 than circulating Tregs, and the numbers of tumor-infiltrating Tregs significantly correlated with the levels of CCL22 in ovarian tumor cell culture supernatants, suggesting their recruitment via a CCR4/CCL22 interaction. CCL22 was mainly produced by tumor cells, macrophages and mDCs in the primary ovarian tumors, and its expression markedly increased in response to IFNgamma. Conclusions: Taken together, the specific recruitment of Tregs, probably triggered by inflammatory stimuli, leads to a significant immune suppression in the advanced stages of ovarian cancer.
Deciphering Treg accumulation in melanoma.
Authors: Tobin Vealey Kristen E. , Le Poole I. Caroline , Klarquist Jared S. , Eby Jonathan M. 
Published: March 2020

e22170 Background: A high density of regulatory T-cells (Tregs) at melanoma tumor sites correlates with poor prognosis due to immunosuppressive effects on the host immune system. While the concentration of circulating Tregs in patients with melanoma is not significantly different from that of healthy controls, Tregs tend to accumulate at tumor sites. We hypothesized that the influx of Tregs observed in melanoma tumors may be explained by enhanced tumor homing. Methods: To quantify the relative expression of chemokine receptors CCL4 and CCL8, and skin homing receptor CLA, blood was drawn from five metastatic melanoma patients and five healthy controls. Lymphocytes were ficolled and negatively sorted for CD3 expression. T-cells were subjected to 7-color FACS staining where Tregs were defined as CD4+CD25+CD127lowFoxP3+ and were simultaneously assessed for expression of CCR4, CCR8, and CLA. To further understand chemokine-receptor signaling involved in Treg homing in melanoma we analyzed the number of CCL22 producing cells in four human metastatic melanoma tissues and four healthy skin tissues obtained during surgery. Dermal CCL22+ cells were detected by indirect immunohistochemistry and quantified to a depth of three times the thickness of the epidermis. Results: Lymphocytes of melanoma patients were found to exhibit enhanced expression of CCR4 (mean of 65.9 versus 51.2%, p<0.01) and CCR8 (3.0 versus 1.5%, p<0.05), but not CLA (21.9 versus 23.9%) as compared with healthy controls. The mean fluorescence intensities of CCR4 and CCR8 were likewise elevated by 63 and 49% over controls (p<0.05 and p<0.01), respectively. A markedly increased number of CCL22 secreting cells were found in tumor samples (mean of 1063.1 versus 207.4, p= 0.02) as compared with healthy controls. Conclusions: These data strongly suggest that enhanced homing of CCR4+ Tregs towards the ligand CCL22 is likely involved in accumulating Tregs at melanoma tumor sites, ultimately impeding effective anti-tumor immune responses. Targeting chemokine-receptor signaling may thus be an effective intervention strategy in melanoma.
Serum chemokine CXCL7 activity after resection of breast cancer.
Authors: Kosir Mary Ann , Ju Donghong 
Published: March 2020

e22182 Background: The chemokine CXCL7 is associated with tumor migration, invasion and angiogenesis and is a ligand for CXCR2. The purpose of the study is to measure changes in serum chemokine CXCL7 from resectable breast cancer patients between preoperative and postoperative blood samples. Methods: With IRB approval, we prospectively collected serum samples from patients undergoing breast cancer surgery immediately preoperatively and at least one week postoperatively. Serum CXCL7 protein concentrations were measured by enzyme-linked immunosorbent assay (ELISA) using human CXCL7/NAP-2 Duo set ELISA Development System (R and D Systems, Minneapolis, MN) according to manufacturer’s instructions. Measurements were performed in duplicate with three separate experiments. Results were analyzed using unpaired and paired Student’s t-Test. Demographic and clinical information were collected. Normal donor samples were from ProteoGenex. Results: Twenty-three matched serum samples were analyzed. The mean age was 52 years (range 36-67), 65.2% were African American, 56.5% underwent partial mastectomy. There were 5 in Stage I, 9 in Stage II, 2 in Stage III, and 7 in Stage 0. Only 4 of 16 with invasive cancer had nodal disease, 11 were ER positive, 6 were triple negative, and 5 of 7 with DCIS were ER positive. Matched serum samples showed greater CXCL7 serum levels in preoperative samples when compared to normal donor samples (9.10 ±0.45 vs 8.10 ± 0.22 ug/ml; mean±sem, p<0.05). The CXCL7 serum levels were significantly decreased in postoperative serum as compared to preoperative serum (8.40 ± 0.47 vs 9.10 ± 0.45 ug/ml; mean±sem, p<0.05) reaching normal donor serum levels. When individual matched pairs of serum were analyzed, 16 showed decrease in postoperative CXCL7 levels compared to preoperative. Conclusions: The chemokine CXCL7 found in serum is increased in breast cancer patients compared to normal donors, and significantly decreases postoperatively to normal levels. This supports translational research of the role of CXCL7 in breast cancer.
Urinary 8-oxoguanine as a predictor of survival in patients undergoing radiotherapy.
Authors: Roszkowski Krzysztof , Olinski Ryszard 
Published: March 2020

e22197 Background: Despite several factors with prognostic value which are available for conventional cancer therapy, there is no test of the outcome of radiotherapy for individual prediction. Usually a certain dose level is prescribed for a whole group of cancer patients with similar diagnosis. This dose is set empirically taking into consideration the most sensitive patients. However, development of a prognostic test would allow to predict in advance which patients may be treated with even a higher dose while in the other case to find another more successful modality. The aim of this work was to investigate whether fractionated radiotherapy of cancer patients (n=99) is responsible for oxidative DNA damage on the level of the whole organism and whether the biomarkers of the damage such as 8-oxo-dG (8-oxo-7,8-dihydro-2’-deoxyguanosine) and its modified base (8-oxo-Gua) in urine and DNA may be used as a predictor of radiotherapy success. Methods: All the aforementioned modifications were analyzed using techniques which involve HPLC/EC or HPLC/GC/MS. Results: Of all analysed parameters only patients with significantly elevated urinary excretion of the 8-oxo-Gua with concomitant unchanged level of 8-oxo-dG in leukocytes DNA in the samples collected 24 h after the first fraction in comparison to the initial level have significantly increased survival time (60 mo. after the treatment, survival of 50% of the patients who fulfill the above mentioned criteria, in comparison with 10% of the patients who did not). Conclusions: Results of our work suggest that patients with higher urinary 8-oxo-Gua and concomitant stable level of 8-oxo-dG in leukocytes DNA, after 24h of the first dose should be regarded as better responder to radiotherapy as being at lower risk of mortality. Impact: The above mentioned statement could make it possible to use these parameters as a markers to predict the clinical success.
The study of in vivo acute effect of two different delivery modalities of iron oxide core with titanium dioxide shell nanoparticles in rabbits liver tumor.
Authors: Refaat Tamer , West Derek , Elachy Samar , Parimi Vamsi , May Jasmine , Harris Kathleen R. , Larson Andrew C. , Omary Reed A. , Paunesku Tatjana , Woloschak Gayle 
Published: March 2020

e22204 Background: To compare intravenous (IV) versus fluoroscopy-guided transarterial intra-catheter (IC) delivery of iron oxide core with titanium dioxide shell nanoparticles (NPs) in vivo in VX2 model of liver cancer in rabbits and detect the NPs distribution and effect of NPs presence on the target tumor and other rabbit’s organs. Methods: After obtaining the IACUC approval, liver tumors were obtained by implantation of tumor tissue obtained from a hind limb VX2 tumor of donor rabbits. NPs were delivered either IV or IC. After rabbit termination, 2 hours post NPs injection, tumor, liver, kidney, lung and spleen were harvested, split in half and a part of it was frozen while the remainder was formalin fixed and paraffin embedded. To assess the NPs distribution in 2D we stained 5um thick paraffin tissue sections using Dopamine-Biotin-DHS histochemical (HC) staining followed by Nanozoomer microscopy analysis. H and E staining, TUNEL assay and Ki67 immunohistochemistry were also done. X-ray Fluorescence Microscopy (XFM) was used to quantify the NPs. Frozen tissue was used for bulk NPs concentration analysis using Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Results: This study included ten rabbits; 3 rabbits had IV NPs injections, 3 had IC NPs injection, 2 control and 2 donors. ICP-MS analysis showed statistically significant higher NPs concentration in tumors of IC arm vs. IV arm (p= 0.0356), while there was higher concentration of NPs in liver (p=0.00077) and spleen (p = 0.01356) of IV vs. IC arms but no difference in kidneys or lungs. These findings were consistent with results from HC and XFM analyses. HC 2D analysis of NPs distribution showed that the RES have taken up the NPs non-specifically. There were no statistically significant differences between the treatment groups regarding the Ki67 proliferation or the TUNEL apoptosis indices or when control rabbits were compared to NPs treated rabbits. Conclusions: Both IV and IC NPs injection are feasible modalities for delivering NPs to tumors with acceptable acute systemic effects and comparable tumor effect. IV delivery increased sequestration of the NPs by RES and their accumulation in spleen and liver.
A pilot chemoprevention study of isopropanolic black cohosh extract in women with ductal carcinoma in situ.
Authors: Hofstatter Erin Wysong , Stavris Karen , Horowitz Nina Ruth , Killelea Brigid K. , Tsangaris Theodore , Lannin Donald R. , Andrejeva Liva , Cong Xiangyu , Yao Xiaopan , Rimm David , Chagpar Anees B. 
Published: March 2020

TPS1609 Background: Recent evidence suggests that black cohosh (Cimicifuga racemosa) may be a potential agent for breast cancer prevention. The active ingredients in black cohosh preparations appear to be triterpene glycosides. Recent preclinical data suggest several mechanisms by which triterpenes may prevent and treat breast cancer, including anti-proliferative, pro-apoptotic, anti-estrogenic, and anti-inflammatory effects. Epidemiologic data demonstrate a significant protective effect of black cohosh against the development of breast cancer in healthy women, and prolonged disease-free survival in breast cancer patients. There is also abundant evidence demonstrating the safety and tolerability of black cohosh in several clinical trials studying its use for treatment of hot flashes. We hypothesize that efficacy of black cohosh can be demonstrated in a pilot pre-operative window trial in a cohort of women with ductal carcinoma in situ (DCIS). Methods: In this trial, we treat women with a 2-5 week pre-operative course of commercial standardized isopropanolic black cohosh extract (20 mg orally twice per day). We aim to demonstrate a reduction in breast epithelial cell proliferation as measured by Ki-67 staining in regions of DCIS using traditional IHC staining and AQUA analysis. We also assess safety and tolerability of black cohosh through monitoring of patient adherence, liver function tests and serum hormone levels. 22 patients will be enrolled onto the trial. Sample size is based on power calculations for the specific study aim of determining the mean change in the levels of Ki67, using a targeted effect size. Assuming a 10% drop-out rate, a sample size of 20 patients will achieve 91% power to detect a 0.8 standard deviation of difference with a two-sided significance level at 0.05 using Wilcoxon signed-rank test. Eligible subjects are pre- and post-menopausal women ≥ 18 years of age newly diagnosed with DCIS histologically confirmed on breast core biopsy, prior to definitive excision. Women who have recently taken any agent known to affect Ki67 levels in the breast (e.g. hormone therapy) are excluded. Enrollment is currently ongoing with 10 of 22 patients accrued. Clinical trial registry number NCT01628536. Clinical trial information: NCT01628536.
Design of the AFFINITY study: A randomized phase III study of a novel clusterin inhibitor, custirsen, plus cabazitaxel/prednisone (CbzP) versus CbzP alone as second-line chemotherapy in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Beer Tomasz M. , Blumenstein Brent A. , Fizazi Karim , Hotte Sebastien J. , Jacobs Cindy , Stewart Patricia S. 
Published: March 2020

TPS5103 Background: Custirsen enhances chemotherapeutic activity via inhibition of clusterin expression. Clusterin is a cytoprotective, antiapoptotic chaperone upregulated by anticancer therapies that confers treatment resistance. In a phase 2 study, mCRPC patients who had progressed within 6 mos of completing first-line docetaxel (DOC)/prednisone (P) and who were retreated with DOC/P and custirsen had a median overall survival of 15.8 mos. Lowering of serum clusterin level during second-line treatment was associated with significantly longer survival. CbzP has recently shown a survival advantage in patients with prostate cancer that has progressed after DOC therapy. The AFFINITY study was designed to evaluate in a larger study whether adding custirsen to CbzP will further improve survival in this patient population. Methods: AFFINITY was initiated in August 2012. Eligible patients in this phase 3, international, multicenter, open-label trial must have received ≥225 mg/m2 of DOC; have progressive disease as defined by RECIST 1.1, bone scan progression, and/or serum prostate-specific antigen level; have metastatic disease of the chest/abdomen/pelvis/bone; have adequate renal and liver function; and have a Karnofsky score ≥70%. Patients may have received up to 1 DOC regimen as well as abiraterone and/or enzalutamide. Approximately 630 patients will receive 21d cycles of Cbz (25 mg/m2IV q21d) + P (10 mg PO/d), either alone or with custirsen 640 mg IV given for 3 loading doses and then weekly until disease progression, unacceptable toxicity, or 10 cycles. The primary efficacy measure is overall survival. The secondary measure is proportion of patients alive without disease progression at Day 140 post-randomization. All efficacy analyses are intent to treat. Adverse events of all patients who receive ≥1 dose of custirsen or Cbz will be included in the safety analysis. This study is sponsored by Teva BPP R&D, Inc., in collaboration with OncoGenex Pharmaceuticals, Inc. Clinical trial information: NCT01578655.
MotHER: A registry for women with breast cancer who received trastuzumab (T) with or without pertuzumab (P) during pregnancy or within 6 months prior to conception.
Authors: Brown Vikki , Partridge Ann , Chu Laura , Szado Tania , Trudeau Caroline , Andrews Elizabeth B 
Published: March 2020

TPS658 Background: T and P are monoclonal antibodies that target different HER2 epitopes. T is approved for treatment of early and metastatic HER2+ BC while P is approved in combination with T for previously untreated HER2+ MBC. Oligohydramnios has been reported in patients (pts) who received T during pregnancy, and also in P-treated pregnant monkeys. Although both antibodies are FDA Pregnancy Category D, indicating evidence of fetal harm, some physicians and pts accept this risk and continue treatment. The MotHER registry was established in 2008 as an FDA postmarketing commitment to evaluate the effects of T therapy on pregnancy outcome; P was included in the study following its approval in 2012. MotHER is the first prospective study of the effects of a targeted cancer therapy on pregnancy outcome. Methods: MotHER is a US registry study of women exposed to T±P during pregnancy or within 6 months prior to conception. Women enroll voluntarily and are followed until pregnancy outcome; infants are followed through the first year of life. Medical information is primarily collected from healthcare providers. Information on potential birth defects noted at birth or during the pediatric follow-up is classified by a birth defect evaluator/clinical geneticist. Enrollment must be initiated before pregnancy outcome. Pts with known prenatal testing results may enroll, but to reduce the potential for bias these pts will be analyzed as a subset. Primary outcomes: number and nature of pregnancy complications, including oligohydramnios, pregnancy outcomes, fetal/infant outcomes and fetal/infant functional deficits. Secondary outcomes: preterm births, elective/therapeutic abortions, miscarriages, fetal growth abnormalities and delivery complications. The study is descriptive and not for formal hypothesis testing; event proportions with CIs will be calculated. The registry will accrue in the US from 2009 to 2019 for T-treated pts and from 2012 to 2022 for P+T-treated pts. The number of potential pts is small therefore physicians are encouraged to refer any eligible pt to increase knowledge about the safety of T±P in pregnancy. herceptinpregnancyregistry.com. Clinical trial information: NCT00833963.