Jihyoun Lee

Targeted gold nanoparticles enhance sensitization of prostate tumors to megavoltage radiation therapy in vivo.

UNLABELLED We report potent radiosensitization of prostate cancers in vitro and in vivo using goserelin-conjugated gold nanorods. Progressive receptor-mediated internalization of conjugated nanorods over time increases the radiation interaction cross-section of cells and contributes to the effects observed in vitro. The low concentrations of gold required, the long interval between injection of nanoparticles and radiation, and the use of megavoltage radiation to generate radiosensitization in vivo foretell the possibility of eventual clinical translation of this approach. FROM THE CLINICAL EDITOR The ability of gold nanoparticles (AuNPs) to enhance the effect of physical radiation dose on tumor cells is known. This radiosensitization effect is thought to result from an increased number of photoelectric absorption events and the increased number of electrons present in gold. The authors here sought to further increase the amount and specificity of gold accumulation in prostatic cancer cells by conjugating gold nanorods to goserelin, a synthetic luteinizing hormone releasing hormone (LHRH) analogue that would bind to the LHRH receptor overexpressed in prostate cancers. It was shown that tumour cells were more sensitive to megavoltage radiation therapy. It is hoped that there would be eventual clinical translation of this approach.

High-Temperature Oxidation of Ti0.3Al0.2N0.5 Thin Films Deposited on a Steel Substrate by Ion Plating

To improve the high-temperature oxidation resistance of STD61 steels used ashot dies or cutting tools, Ti0.3Al0.2N0.5films were deposited on STD61 steel substrates by arc-ion plating. Thedeposited film consisted of Ti3Al2N2 andTi2N phases. The oxidation characteristics were studied attemperatures ranging from 700 to 900°C in air. The deposited STD61steels displayed excellent oxidation resistance up to 800°C, butexhibited large weight gains and breakaway oxidation at 900°C. Theoxidation products were primarily Fe2O3, TiO, TiO2,and α-Al2O3, the relative amount of each oxidebeing dependent on the oxidation condition. Among various oxides, TiO2and α-Al2O3 were the major oxides at 800°Cfor at least up to 16 hr. However, at a higher temperature or a longeroxidation period, the significant outward diffusion of iron from thesubstrate resulted in the formation of iron oxides, together with otheroxides of Ti and Al.

Skin-sparing mastectomy and immediate latissimus dorsi flap reconstruction: a retrospective analysis of the surgical and patient-reported outcomes

BackgroundSkin-sparing mastectomy (SSM) and latissimus dorsi (LD) flap immediate breast reconstruction (IBR) is a tailored surgical procedure. The surgical and patient-reported outcome (PRO) of SSM and LD IBR were assessed.MethodsRetrospective data of 146 SSMs performed by a single surgeon was reviewed. Among patients included in the data, 65 patients underwent SSM and LD IBR without a prosthetic implant. A survey estimating the degree of patient satisfaction (poor, fair, good, and excellent) as regards the cosmetic outcomes of surgery was performed. The patients were divided into two groups according to their degree of satisfaction (excellent group versus non- excellent group), and analysis was done to identify factors affecting the highest patient satisfaction.ResultsThe mean age of the patients was 48.4 years, and pathological results were: infiltrating ductal carcinoma (n = 48, 73.8%), ductal carcinoma in situ (n = 15, 23.1%), and others (n = 2, 3.1%). One patient received postmastectomy radiotherapy. After a mean follow-up of 34 months, no local recurrence occurred. There was no skin necrosis or LD flap loss. Donor site morbidities were seroma (n = 8, 12.3%), scarring (n = 8, 12.3%), and back pain (n = 6, 9.2%). Fifty patients (76.9%) were satisfied and 40% reported their degree of satisfaction as excellent. Breast symmetry (P <0.001), nipple cosmesis (P <0.001), visual difference of bilateral breasts (P = 0.021), and panel assessment score (P <0.001) were factors that affected the highest patient satisfaction.ConclusionsOur SSM and LD IBR was safe, with no local recurrence and low morbidities, and produced a sufficiently high level of patient satisfaction. Achieving breast symmetry and nipple cosmesis would be the key to meeting the patient’s expectation.

Interdigitating dendritic cell sarcoma occured alone in axilla.

Interdigitating dendritic cell sarcoma (IDCS) is a very rare disease around the world and its prognosis is known to be aggressive. This reports a case diagnosed as IDCS of the axillary region treated in Soonchunhyang University Hospital. A 57-year-old female visited Soonchunhyang University Hospital with a left axillary mass. The mass was hard and fixed. Computed tomography observed a 7 cm lymph node at the left axilla, and core biopsy suspected sarcoma. In another study, there was no specific finding except the axillary lesion. Left axillary lymph node dissection (level I, II) was conducted and the pathologic report finally showed IDCS. The patient was treated with only radiotherapy and followed up without recurrence for 13 months up to now. IDCS is a very rare sarcoma that is hard to diagnose and progresses fast. Thus, treatment is very difficult. Proper treatment can be better established after more experiences.

Influence of the Angelina Jolie Announcement and Insurance Reimbursement on Practice Patterns for Hereditary Breast Cancer

Lack of awareness, the stigma of carrying a genetic mutation, and economic factors are barriers to acceptance of BRCA genetic testing or appropriate risk management. We aimed to investigate the influence of Angelina Jolies announcement of her medical experience and also health insurance reimbursement for BRCA gene testing on practice patterns for hereditary breast and ovarian cancer (HBOC). A survey regarding changes in practice patterns for HBOC before and after the announcement was conducted online. The rate of BRCA gene testing was obtained from the National Health Insurance Review and Assessment Service database. From May to August 2016, 70 physicians responded to the survey. Genetic testing recommendations and prophylactic management were increased after the announcement. Risk-reducing salpingo-oophorectomy and contralateral prophylactic mastectomy was significantly increased in BRCA carriers with breast cancer. The BRCA testing rate increased annually. Health insurance and a celebrity announcement were associated with increased genetic testing.

Reproductive factors as risk modifiers of breast cancer in BRCA mutation carriers and high-risk non-carriers

This study was conducted to identify the role of reproductive factors as environmental modifiers for breast cancer (BC) risk in clinic-based, East-Asian BRCA1 and BRCA2 mutation carriers and non-carriers with high-risk criteria of BRCA mutations (family history (FH) of BC, early-onset BC (aged ≤40 years)). A total of 581 women who were BRCA carriers (222 BRCA1 and 359 BRCA2), 1,083 non-carriers with FH, and 886 non-carriers with early-onset BC were enrolled and interviewed to examine the reproductive factors, from 2007 to 2014. The hazard ratio (HR) and its 95% confidence interval (CI) in the weighted Cox regression model were used to calculate the BC risk based on the reproductive factors. Earlier menarche increased BC risk by 3.49-fold in BRCA2 mutation carriers (95%CI=2.03–6.00) and 3.30-fold in non-carriers with FH (95%CI=1.73–6.34), but was insignificantly associated with BRCA1 carriers and non-carriers for early-onset BC (P-heterogeneity=0.047). Higher parity decreased BC risk in BRCA carriers and non-carriers with FH, especially in BRCA1 carriers (HR=0.27, 95% CI=0.09–0.83 for two parity; and HR=0.23, 95%CI=0.05–1.00 for ≥3 parity), but increased the early-onset BC risk (HR=4.63, 95%CI=2.56–8.51 for >3 parity, p-heterogeneity=0.045). Oral contraceptive (OC) use and longer estrogen exposure periods (≥30 years) were associated with an increased risk of early-onset BC (HR=3.99, 95%CI=1.65–9.67; HR=7.69, 95%CI=1.96–25.01), while OC use was not associated with BC risk in other groups and longer estrogen exposure had rather decreased risk for BC risk (both p-heterogeneity<0.001). Several reproductive factors as risk modifiers could heterogeneously be associated with BC among BRCA1/2 mutation carriers, non-carriers with FH, and early-onset BC non-carriers.

Development of second primary cancer in Korean breast cancer survivors

Purpose Breast cancer survivors have slightly increased the risk of second primary cancers. Breast, colon, uterine, and ovarian cancers are common secondary cancers in breast cancer survivors. In this study, we assessed the development of second primary cancers of breast cancer survivors in Korea. Methods Medical records of patients with breast cancer in 3 tertiary medical institutions were reviewed retrospectively. We evaluated secondary malignancy diagnosed at least 2 months after the breast cancer diagnosis. Based on the International Classification of Disease-9 codes of malignancies, secondary primary breast cancer records were evaluated with person-year adjustment. The standardized incidence ratio (SIR) was assessed using national cancer incidence. Results A total of 3,444 treatment records were included from 3 medical centers. The cumulative incidence of overall second primary cancers was 2.8% (n = 93). The SIR was significantly higher in all sites (1.56; 95% confidence interval [CI], 1.26–1.91), endometrial cancer (5.65; 95% CI, 2.06–12.31), biliary tract cancer (3.96; 95% CI, 1.19–8.60), and thyroid cancer (2.29; 95% CI, 1.67–3.08). Conclusion The incidence of cancer was higher in breast cancer survivors compared to general population. Surveillance of secondary cancer in this group should be recommended individually considering the benefit related to the prognosis of primary breast cancer.

Abstract 2051: Three-dimensional in vivo photoacoustic tracking of targeted nanoparticles in a pancreatic cancer model

The use of targeted gold nanoparticles (AuNPs) has shown tremendous promise in the early detection and improved therapy of cancer. Successful development and implementation of these new theranostic approaches, however, depends on sufficient transvascular migration and specific accumulation of AuNPs to extravascular tumor tissue. This study utilized photoacoustic (PA) imaging to track - in three dimensions and through 24 hours - the extravasation and accumulation of targeted AuNPs in a subcutaneous murine model of prostate cancer. AuNPs (nanorods; 760-nm peak) targeting the Luteinizing-hormone-releasing hormone receptor were systemically injected into three mice bearing PC-3 human prostate cancer tumors; as a control, three additional mice were injected with PEGylated AuNPs. For all particle-tracking studies, multi-wavelength (680, 760, 800, 920, & 940 nm), volumetric (spherical volume with 25.6-mm diameter) PA imaging was conducted at pre-injection, post-injection, 15-min, 60-min, 240-min, and 24-hr time points; the imaging volume contained the tumor and the spleen (control). Following imaging, tumors were excised and inductively coupled plasma mass spectrometry (ICP-MS) of samples and two-photon imaging of histological sections was performed to confirm AuNP accumulation and diffusion, respectively. Volumetric PA perfusion assessment was then conducted by monitoring the wash-out of indocyanine green (ICG) in near real-time (0.25 Hz for 180 s post-injection). All PA imaging studies were performed on the Nexus 128 preclinical imaging system (Endra Inc., Ann Arbor, MI). Spectral unmixing of the multi-wavelength PA data was achieved to segment AuNPs and deoxy-/oxyhemoglobin (i.e. for local hypoxia assessment). Accumulation and extravasation data of the targeted AuNPs in the tumor were then compared to tumor perfusion data, PA-derived tumor hypoxia data, PEGylated AuNP accumulation data in the tumor, AuNP accumulation data in the spleen, and ICP-MS/histological analysis. Results of the study establish that volumetric PA imaging with multi-wavelength unmixing is able to track nanoparticle accumulation and extravasation throughout an in vivo tumor model. The location and relative degree of particle accumulation was also found to correlate with PA-based perfusion and vascularity assessment. This study demonstrates that volumetric PA imaging has the spatiotemporal resolution and sensitivity to track extravasation of AuNPs in an in vivo tumor model. This in vivo tracking ability - along with concurrent PA-based perfusion and hypoxia mapping - could be of significant benefit in understanding and improving nanoparticle targeting for the diagnosis and treatment of cancer. Citation Format: Richard Bouchard, Tatiana Wolfe, Michael Thornton, Timothy Morgan, Trevor Mitcham, Shanta Bhattarai, Jonathan Grant, Jihyoun Lee, John Hazle, Sunil Krishnan. Three-dimensional in vivo photoacoustic tracking of targeted nanoparticles in a pancreatic cancer model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2051. doi:10.1158/1538-7445.AM2014-2051

Pegfilgrastim for primary prophylaxis of febrile neutropenia in breast cancer patients undergoing TAC chemotherapy

Purpose Primary prophylaxis with granulocyte colony-stimulating factor can effectively prevent febrile neutropenia (FN) during breast cancer treatment. The aims of this study were to evaluate the incidence of FN and the ANC profile in patients undergoing chemotherapy and pegfilgrastim primary prophylaxis. Methods Patients receiving 6 cycles of adjuvant docetaxel, doxorubicin, and cyclophosphamide (TAC) chemotherapy were included in this study. Pegfilgrastim was administered with analgesics 24 hours after treatment. Laboratory tests were performed on day 0 (before chemotherapy) and ANC was measured daily starting day 5 until it were restored to 1,000/mm3. Bone pain was checked via the numeral rating scale (NRS). Results A total of 61 patients and 366 cycles were evaluated. Mean age was 49.2 ± 7.1 years. FN was seen in 5 patients (16.4%) and 12 cycles (3.3%) with pegfilgrastim. Grades 3 and 4 neutropenia was seen in 91.5% of cycles with FN. The ANC nadir was most commonly seen at day 7 and the mean ANC nadir depth was 265.7/m3. Age was negatively correlated with nadir depth (r = −0.137, P = 0.009). Severe pain higher than NRS 7 occurred in less than 20% of patients after the administration of pegfilgrastim. Conclusion Incidence of FN was low during the chemotherapy by primary prophylaxis with pegfilgrastim. The ANC nadir was seen on day 7 after chemotherapy. Bone pain with pegfilgrastim was well tolerated during TAC chemotherapy.

Nationwide Analysis of Treatment Patterns for Korean Breast Cancer Survivors Using National Health Insurance Service Data

Background The National Health Insurance Service (NHIS) established a healthcare claim database for all Korean citizens. This study aimed to analyze the NHIS data and investigate the patterns of breast cancer treatments. Methods We constructed a retrospective female breast cancer cohort by analyzing annual incident cases. The annual number of newly diagnosed female breast cancer was compared between the NHIS data and Korea National Cancer Incidence Database (KNCIDB). The annual treatment patterns including surgery, chemotherapy, radiation therapy, endocrine therapy and targeted therapy were analyzed. Results A total of 148,322 women with newly diagnosed invasive breast cancer during 2006–2014 was identified. The numbers of newly diagnosed invasive breast cancer cases were similar between the NHIS data and KNCIDB, which demonstrated a strong correlation (r = 0.995; P < 0.001). The age distribution of the breast cancer cases in the NHIS data and KNCIDB also showed a strong correlation (r = 1.000; P < 0.001). About 85% of newly diagnosed breast cancer patients underwent operations. Although the proportions of chemotherapy use have not changed during 2006–2014, the total number of chemotherapy prescriptions sharply increased during this period. The proportions of radiotherapy and anti-hormonal therapy increased. Among the anti-hormonal agents, tamoxifen was the most frequently prescribed medication, and letrozole was the most preferred endocrine treatment in patients aged ≥ 50 years. Conclusion Along with the increased breast cancer incidence in Korea, the frequencies of breast cancer treatments have increased. The NHIS data can be a feasible data source for future research.