Do Molecular Subtypes of Breast Cancer Affect Outcomes Following Hypofractionation or Conventional Fractionation Radiation Therapy?

Introduction Molecular subtypes of breast cancer (BC) are well-established prognostic markers in early-stage BC patients. The addition of radiation therapy (RT) to breast-conserving surgery has improved outcomes in this patient population, with conventional fractionation (CF) and hypofractionation (HF) regimens displaying comparable morbidity and mortality. However, most studies have not taken into account molecular subtype. Thus, it is still unknown if outcomes are similar between CF and HF for each molecular subtype. Herein, the effects of molecular subtype on the efficacy of CF and HF radiotherapy regimens for early-stage BC patients receiving adjuvant RT was investigated. Methods A retrospective review of stage I/II BC patients who received surgical intervention (breast conservation surgery or mastectomy) followed by RT at UNMC between 2010 and 2017 was conducted. Demographics, tumor characteristics, treatment data (course and dose of radiotherapy), and outcomes information (progression and survival) were collected. Cumulative incidence function and Kaplan-Meier testing were used to assess recurrence and survival, respectively. Variables were then further analyzed using univariate and multivariable COX proportional hazard models. Results In total, 311 patients met the inclusion criteria, including 211 CF and 100 HF patients. Patients undergoing HF were of lower stage and grade, but increased age. Rates of locoregional recurrence, distant recurrence, and survival were similar between cohorts. When stratifying based on molecular subtype, no differences in recurrences or survival were observed. On multivariable analysis, only stage was a significant predictor of distant failure and survival. Conclusions Although patient numbers were low, these findings suggest that HF and CF are equally efficacious in controlling locoregional recurrence in early stage BC patients. Thus, a hypofractionated regimen for radiation therapy should be considered an option regardless of molecular subtype in early stage BC following breast conserving surgery

Mid-morning Break and Poster Sessions: Family Gambling and its Connection to Intergenerational Family Relationship Building

Introduction Most research has viewed gambling as an individual activity and very little research has been devoted to the impacts of family gambling. Bengtson and Roberts (1991) viewed intergenerational family solidarity as a comprehensive construct consisting of six components of solidarity. Affectual, Associational, and Functional solidarities, can be adapted to a gambling context. The three family solidarity dimensions of affection, association, and function are the core components to family solidarity (Hogerbrugge & Komter, 2012)

Polymeric Chloroquine: Modifying an Old Drug to Make It a Little Sweeter

Hydroxyethyl starch (HES) is a clinically used polysaccharide colloidal plasma volume expander. The goal of this study was to synthesize HES modified with hydroxychloroquine (HCQ) as a novel polymeric drug with the ability to inhibit the invasive character of pancreatic cancer (PC) cells. HES was conjugated with HCQ using a simple carbonyldiimidazole coupling to prepare Chloroquine-modified HES (CQ-HES). CQ-HES with various degrees of HCQ substitution were synthesized and characterized. In vitro studies showed CQ-HES to have a similar toxicity profile as HCQ. Confocal microscopy revealed the propensity of CQ-HES to localize to lysosomes, and mechanistic studies confirmed the ability of CQ-HES to inhibit autophagy in PC cells similar to HCQ. Further studies demonstrated a greatly enhanced ability of CQ-HES to inhibit the invasion of PC cells when compared with HCQ. No significant HCQ release from CQ-HES was observed, which confirmed that the observed activity was due to the action of CQ-HES as a polymeric drug. Pharmacokinetic (PK) studies showed that CQ-HES preferentially distributed to the liver and kidney but had limited ability to alter distribution to tumors. Furthermore, levels observed in the eyes were 2-4 times higher when administering HCQ than CQ-HES. In an orthotopic syngeneic model of PC, the addition of CQ-HES to gemcitabine therapy reduced primary tumor growth and prolonged survival. Additionally, mice who received HCQ showed significantly higher levels of HCQ in the eyes compared to CQ-HES. Complete blood count and complete metabolic profiles did not identify any organ or tissue dysfunctions in mice receiving CQ-HES. Further pathohistological analysis confirmed the safety of CQ-HES as no microscopic indications of augmented tissue damage were observed. Lastly, pretreatment sensitization with CQ-HES improved survival in the setting of stereotactic body radiation therapy. Thus, CQ-HES appears to be safe, improves outcomes of radiation and chemotherapy, and reduces HCQ exposure to the eye, which may help prevent retinopathy

Discipline

I make delicate but often sinister sculptural works that evoke latent sexual drives through odd combinations of materials, objects, and proximities. Vintage objects from the domestic context- furniture, clothing, and personal [accoutrements] - are conjoined in ways that concretize and make visible their strange functions and corresponding social expectations. My works acknowledge the educational properties of objects and provoke an analysis of the ways we intuit information about societal expectation through observation of our surroundings. As the functions of these objects are frequently ambiguous, they suggest similarly ambiguous but unsettling information about their implicit connotational expectations. The objects exist as instruments, compensations, and residual artifacts of the negotiation between individual interests and societal constraints. &nbsp; The body is the site and mediator of all psychological and social experience; sexuality is the site where the body and power negotiation intersect. The body is the site and instrument of expectation and punishment, even where the body is not touched directly ; the body is the physical space through which intangible motivations, desires, considerations, and infractions are mediated and controlled. Many of the instruments used to impose societal and behavioral discipline refer to the body, and most of the objects included in my works refer either directly or indirectly to bodily contact. These objects are an examination of the somatic and psychological negotiation of power- the acquiring, maintaining, or giving of power or control.</p

Radiation Therapy Improves Local Control in Juvenile Nasopharyngeal Angiofibroma following Disease Progression after Embolization and Surgical Resection: A Case Report

Juvenile nasopharyngeal angiofibroma (JNA) is a relatively uncommon, benign neoplasm of the nasopharynx that can be very difficult to diagnose early due to inconspicuous and seemingly harmless presenting symptoms. Early diagnosis and treatment of JNA are essential for a good prognosis. JNA typically responds well to radiation therapy (RT), but when it does not, the most appropriate next course of action has not been readily defined due to the limited occurrence and experience with this neoplasm. Herein, we describe a JNA patient, who continued to progress after surgery and 36 Gy of adjuvant radiation, but after an additional 14.4 Gy, he has remained in remission for over 2 years. An 11-year-old boy who presented with JNA underwent treatment with embolization and surgical resection. Unfortunately, the tumor progressed within 2 months of surgical intervention and he required RT for adequate local control. While undergoing RT, he again demonstrated signs of progression; so his radiation regimen was increased from 3,600 cGy in 20 fractions to 5,040 cGy in 28 fractions. Since completing RT, the tumor has continued to decrease in size, and the patient is stable and has been without signs of disease progression for over 24 months now. Thus, escalating the radiation regimen to 5,040 cGy may improve local control in rapidly progressive JNA

Highly Aggressive and Radiation-Resistant, “Atypical” and Silent Pituitary Corticotrophic Carcinoma: A Case Report and Review of the Literature

Background: Pituitary tumors typically remain silent unless interaction with nearby structures occurs. Rare subsets of pituitary tumors display aggressive phenotypes: highly mitotic, locally invasive, metastatic, chemotherapy and radiation resistant, etc. Disease progression and response to therapy is ill-defined in these subtypes, and their true prognostic potential is debated. Thus, identifying tumor characteristics with prognostic value and efficacious treatment options remains a challenge in aggressive pituitary tumors. Case Presentation: A 45-year-old female presented with a nonfunctioning corticotropic pituitary macroadenoma with biomarkers suggestive of an “atypical” subtype: Ki-67 of 8–12%, increased mitosis, and locally invasive. Despite resections and radiation, growth continued, eventually affecting her vision. Although histologically ACTH positive, the patient remained clinically asymptomatic. Twelve months later, an episode of Cushing’s disease-induced psychosis prompted a PET-CT scan, identifying sites of metastasis. Temozolomide was added to her medical regimen, and her metastatic liver lesions and boney metastases were treated with radiofrequency ablation and stereotactic body radiation therapy, respectively. Systemic treatment resulted in a drop in her ACTH levels, with her most recent scans/labs at 12 months following RFA suggesting remission. Conclusions: This is a unique presentation of a pituitary tumor, displaying characteristics of both clinically silent corticotropic and “atypical” macroadenoma subtypes. Although initially ACTH positive while clinically silent, the patient’s disease ultimately recurred metastatically with manifestations of Cushing’s disease and psychosis. With the addition of temozolomide to her treatment plan, her primary and metastatic sites have responded favorably to radiation therapy. Thus, the addition of temozolomide may be beneficial in the treatment of aggressive pituitary tumors