Citations

AbstractObjectiveThe established link between oestrogen and breast cancer occurs via both oestrogen receptor (ER)‐mediated and non ER‐mediated mechanisms. The term genotoxic estrogens describes mutagenic metabolites, including oestrogen catechols and quinones, which have been linked to breast carcinogenesis in post‐menopausal women. We aimed to assess whether the route of administration of 17β oestradiol (E2) affects the accumulation of genotoxic oestrogen metabolites in a model of ovarian failure in young girls with Turner syndrome.MethodsStored plasma samples obtained at 0 and 12 months were used from 40 adolescents with Turner syndrome who participated in a 12 months randomized controlled trial of the metabolic impact of E2 orally (2 mg/d) vs transdermally (100 µg/d); dose escalation allowed matching of unconjugated E2 levels in the parent study. We measured 12 oestrogen metabolites (total concentrations = conjugated and unconjugated) using a highly sensitive LCMSMS assay. Results from 48 normally menstruating adolescents were used for comparison.ResultsAfter treatment, least square mean (SE) total E2 concentrations were higher in the oral vs transdermal group (6784 pmol/L vs 1123 [1614], P < 0.0001), as was oestrone (E1) (91 060 pmol/L vs 19 278 [16 534], P < 0.0001). Also, higher after oral treatment were catechol‐oestrogens 4‐hydroxy‐E2 (149 vs 28 [±49] pmol/L), 2‐hydroxy‐E2 (300 vs 76 [±52]), 4‐hydroxy‐E1 (450 vs 105 [±113]), 2‐hydroxy‐E1 (3094 vs 740 [±684]) and 16α‐hydroxy‐E1 (3,007 vs 157 [±534]) (<0.001 between groups). Levels were much closer to controls in the transdermal group.ConclusionsCommon feminizing doses of oral oestradiol for 12 months result in substantial accumulation of unphysiologic, genotoxic oestrogens compared to transdermal oestradiol, expanding concerns about oral oestrogens’ first hepatic passage. Further studies assessing long‐term risks of these metabolites in women taking different forms of oestrogen are needed.

Objectives: To validate a neck-shaft angle (NSA) correction formula using the known angle between the medullary nail and lag screw of an indwelling cephalomedullary nail (CMN). Methods: Pertrochanteric femur fractures were created in 7 synthetic femurs and reconstructed with a CMN. Anteroposterior x-rays were taken with the proximal femur in 0, 15, 30, and 45 degrees of internal/external rotation and 10 and 20 degrees of flexion with neutral rotation. The femoral NSA and the nail angle were measured on anteroposterior x-rays. The corrected NSA was obtained by multiplying the known nail angle by the quotient of the measured NSA over the measured nail angle. Results: With increasing degrees of internal or external rotation, the difference between the actual and the measured NSA increased. After correction using the known angle of the nail, the measured NSA was reduced to within 3 degrees of the actual NSA over all degrees of rotation. At neutral rotation, 15 degrees of external rotation, and 10 and 20 degrees of hip flexion, there was minimal difference between the actual NSA and the measured NSA, negating the effect of the correction formula. Conclusions: The measured NSA after CMN of intertrochanteric fractures is altered by hip rotation. This study validates the correction formula, which determines this difference by using the known angle between the lag screw and the nail.

65 Background: We need better methods to understand the social determinants of health and integrate psychosocial and economic sequelae of cancer and its treatment into healthcare delivery for ethnoculturally diverse population. A Patient-Reported Outcomes Quality of Life (PROQOL) instrument has been developed to capture less commonly discussed patient concerns (Personal Relationships, Emotional health, Physical health, Cancer diagnosis and treatment, Money and Care planning) and improve patient-provider communication. We sought to adapt this instrument and pilot it in underserved, ethnically diverse solid tumor and hematological malignancies patients at Maricopa Integrated Health System (MIHS) in Phoenix, AZ. Methods: Two focus groups (FG) were conducted to understand patient perspectives of an adapted Spanish version of PROQOL. This version was then piloted among patients on active cancer treatment. Patients also completed a Linear Analog Scale Assessment (from 1-10) for quality of life (QOL) and its domains (higher scores indicate better QOL). Results: All participants in both FG (11/12 female) were Hispanics, with a median age of 53 years. Participants agreed that the domains covered in the PROQOL represented the most important psychosocial needs in their cancer continuum. No difficulty in understanding the individual domains or questions for delving deeper into each domain was noted. Median age of 34 pilot study participants (74% female) was 48 years, 79% were Hispanic, 10% were African Americans and median household income was $ 43,924 (range 23,002-98,382). 28/34 completed the Spanish version. Most common concerns were ‘Money’ (32%): difficulty paying medical bills and non-medical expenses and ‘Cancer Diagnosis, Treatment and Survivorship’ (32%): type of cancer and treatment concerns. Median overall QOL was 8 (range 3-10). Conclusions: PROQOL is feasible for systematic capture of patient concerns in underserved, ethnic minority cancer patients. A better understanding of these challenges can help design interventions to improve psychosocial and financial outcomes for the vulnerable groups and decrease disparities in care delivery.

e21079 Background: Increased emphasis is being placed on patient centered outcomes. There is little existing literature on the patient population's prioritization of outcomes in skin cancer care. A PCORI-supported Patient Outcomes Summit was organized to address this. Methods: Patients were recruited from patient support groups, solicitation of ASDS member practices, as well as personal recruitment of patients from the practices of the investigators. A one-day Patient Outcome Summit was convened in Arlington, VA in August 2016. Patients attendees were given orientation to existing outcomes for skin cancer as well as the Delphi process. They then participated in a two round Delphi process by run non-physician facilitators (AB and EA). Group discussion was used to solicit outcomes for inclusion in the rating rounds. Outcomes were then rated anonymously on a 1 (lowest relevance) to 9 (highest relevance) scale. Patients were then able to view the anonymous feedback of the group and rerate the items as they deemed fit based on the group feedback. Results: 21 patients participated in the Delphi process (5 men and 21 women). 10 were melanoma and 11 were non-melanoma patients. 56 treatment related outcomes and themes were identified. The ten most highly rated themes are shown in the table. Conclusions: The first ever skin cancer patient outcome summit was convened to address the lack of patient-centered data in the skin cancer literature and guide measure development. Some traditional outcomes (recurrence) were identifiend. However, the majority of the themes rated most important by the patient attendees center around inclusion of the patient in the decision making process and the physician-patient communication. Increased emphasis and education in these domains may drive increased patient satisfaction in skin cancer care. [Table: see text]

TPS4591 Background: Radical cystectomy is the standard of care for patients with BCG-unresponsive high risk non-muscle invasive bladder cancer (NMIBC). Based on the reported efficacy of atezolizumab in metastatic urothelial carcinoma and the known expression of PD-L1 expression in NMIBC after BCG therapy, this trial will evaluate the activity of atezolizumab in BCG-unresponsive high risk NMIBC. Methods: This is a single arm phase II trial testing systemic atezolizumab (1200 mg IV) every 3 weeks for one year in 135 patients with BCG-unresponsive high risk NMIBC. The study will enroll 70 patients with CIS (with or without concomitant Ta/T1) and 65 with Ta/T1 only. Patients with CIS at baseline will undergo mandatory repeat biopsy at 6 months, and all other patients only for suspected recurrence. Patients with persistent CIS, high grade Ta/T1 recurrence or progression to muscle invasive or metastatic disease will be taken off treatment. The co-primary endpoints are: (1) complete response (CR) at 6 months in the CIS subgroup, and (2) event-free survival (EFS) at 18 months in the overall population. A hierarchical approach will be used to test the two co-primary endpoints. Secondary endpoints include duration of CR as well as progression-free, cystectomy-free, bladder cancer-specific and overall survival in all patients. Response will be correlated to expression of PD-L1 and CD8 by IHC, and to molecular subtypes and immune signatures by RNA-sequencing. Results: If ≥28 (40%) CIS patients respond, the agent will be considered promising. This design has a significance level of 4.6%, and a power of 96%. If the lower bound of the 90% confidence interval of the 18-month EFS excludes 20%, the investigators will conclude the regimen significantly improves EFS relative to historical data (type I error rate 0.05 and statistical power 0.93). Conclusion:Successful completion of this trial could lead to a new treatment paradigm for patients with BCG-unresponsive high risk NMIBC. Funding: NIH/NCI grants: CA180888, CA180819, CA180820, CA180821, and CA180863. Clinical trial information: NCT02844816.

TPS4138 Background: Apatinib is an orally administered, highly selective tyrosine kinase inhibitor of VEGFR-2 that has been studied in many clinical trials, primarily in China, treating various solid tumors. Based on the results of the Chinese Phase 3 study, apatinib was approved in China for the treatment of advanced gastric cancer (GC), but apatinib has yet to be evaluated in a randomized placebo-controlled study in the rest of the world. ANGEL is a multinational, placebo controlled, Phase 3 study investigating the efficacy and safety of apatinib in advanced GC patients in North America, Europe, and Asia Pacific. Methods: Main eligibility criteria include patients with advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction for whom at least 2 prior lines of standard chemotherapy had failed, ECOG performance status ≤ 1, and disease progression < 6 months after last chemotherapy treatment. Approximately 459 patients will be randomized in a 2:1 ratio to receive continuous 28-day cycles of apatinib 700 mg or a matched placebo daily with best supportive care until disease progression, intolerable toxicity or withdrawal of consent. Stratification factors include geographic region (Asia vs. North America/Europe), disease measurability, prior ramucirumab treatment, and treatment therapy line (3rd or 4th). Primary endpoint is overall survival (OS) in the intent-to-treat population, and secondary endpoints are progression free survival (PFS), objective response rate (ORR), disease control rate (DCR), quality of life, and safety. The primary analysis of OS will be conducted in intention-to-treat population using a stratified log-rank test at the two-sided alpha = 0.05 level of significance. If the primary analysis of OS is statistically significant, then PFS and ORR will be analyzed. All other secondary efficacy endpoints will be analyzed using two-sided tests at the alpha = 0.05 level of significance. Enrollment opened Feb 2017. Clinical trial information: NCT03042611.