"I've had constant fears that I'll get cancer": the construction and experience of medical intervention on intersex bodies to reduce cancer risk.

PURPOSE: This paper examines the subjective experience of medical interventions on intersex bodies to reduce cancer risk. METHODS: Twenty-five individuals with intersex variations took part in semi-structured interviews, analysed through thematic discourse analysis. RESULTS: Intersex bodies were positioned as inherently sick and in need of modification, with cancer risk legitimating surgical and hormonal intervention. This resulted in embodied shame, with negative impacts on fertility and sexual wellbeing. However, many participants resisted discourses of bio-pathologisation and embraced intersex status. Some medical interventions, such as HRT, were perceived to have increased the risk of cancer. Absence of informed consent, and lack of information about intersex status and the consequences of medical intervention, was positioned as a human rights violation. This was compounded by ongoing medical mismanagement, including health care professional lack of understanding of intersex variations, and the objectification or stigmatization of intersex people within healthcare. The consequence was non-disclosure of intersex status in health contexts and lack of trust in health care professionals. CONCLUSIONS: The legitimacy of poorly-evidenced cancer risk discourses to justify medical intervention on intersex bodies needs to be challenged. Healthcare practitioners need to be provided with education and training about cultural safety practices for working with intersex people.

Disrupted identities, invisibility and precarious support: a mixed methods study of LGBTQI adolescents and young adults with cancer.

BACKGROUND: Lesbian, gay, bisexual, transgender, queer and intersex (LGBTQI) adolescents and young adults (AYAs) with cancer report higher levels of depression and anxiety and lower health related quality of life than non-LGBTQI AYAs with cancer, and LGBTQI adults with cancer. This mixed methods study examined LGBTQI AYAs' experiences of cancer and cancer care, to understand these health disparities. METHODS: Online surveys were completed by 95 LGBTQI AYAs with cancer (age 16-39 years); 19 AYAs took part in a one-to-one semi structured interview. Reflexive thematic analysis of interviews and open-ended survey responses facilitated in-depth examination of subjective experiences; descriptive statistics performed on individual closed-ended survey items identified the percentage of AYAs reporting experiences identified in the qualitative analysis. RESULTS: 63% of AYAs reported high or very high distress on the K10. Three themes were identified in the qualitative analysis: 1) "Identities in flux", included subthemes "Cancer disrupts developing identities, and involvement with LGBTQI communities"; "Internalized prejudice impacts identities"; and "Cancer facilitates identities and embodiment". 2) "Invisibility in cancer care", included subthemes "Navigating disclosure amongst cis-heteronormative assumptions", "Discrimination and paternalistic cancer care" and " Cis-heteronormativity within cancer information". 3) "Precarious social support for LGBTQI AYAs with cancer", included subthemes " Social support during cancer is helpful for LGBTQI AYAs", "LGBTQI AYAs navigate limited support", and" Finding cancer peer support networks is difficult for LGBTQI AYAs". CONCLUSIONS: LGBTQI AYAs with cancer experience psychosocial vulnerabilities related to identity development, experiences of care, and social support networks. These factors likely contribute to their previously evidenced elevated risk of distress, relative to both non-LGBTQI AYAs and LGBTQI older adults. AYAs affected by cancer may require additional, tailored supportive care, including targeted information resources, LGBTQI AYA specific cancer support groups, or partnerships and referrals to LGBTQI community organisations. Additionally, it is evident that health care professionals and cancer services have much work to do in ensuring LGBTQI AYAs receive affirming and appropriate care across paediatric and adult clinical settings. They must move beyond assuming all patients are cisgender, heterosexual and do not have intersex variations unless otherwise stated; work to signal inclusivity and facilitate disclosure; and be able to respond appropriately with tailored information and care, which is inclusive of LGBTQI partners, chosen family, and support systems.

Almost invisible: A review of inclusion of LGBTQI people with cancer in online patient information resources.

OBJECTIVE: This review assessed the inclusion of lesbian, gay, bisexual, trans, queer and/or intersex (LGBTQI) people in online cancer information. METHODS: The websites of Australian cancer organizations were reviewed to identify if they included LGBTQI people and the extent and nature of this inclusion. Websites that did not include LGBTQI people were then reviewed to identify if information was implicitly LGBTQI inclusive. International LGBTQI cancer information resources were reviewed to identify key content. RESULTS: Of sixty-one Australian cancer organization websites reviewed, eight (13%) mentioned LGBTQI people, including 13 information resources targeted to LGBTQI people and 19 general cancer information resources that mentioned LGBTQI people. For Australian cancer websites that did not mention LGBTQI people, 88% used gender neutral language to refer to partners, 69% included a range of sexual behaviours, 13% used gender neutral language when referring to hormones or reproductive anatomy but none acknowledged diverse relationship types. Internationally, 38 LGBTQI-specific cancer information resources were identified. CONCLUSIONS: Cancer patient information resources need to be LGBTQI inclusive. LGBTQI-targeted resources are required to address this population's unique needs and improve cultural safety and cancer outcomes. PRACTICE IMPLICATIONS: Recommendations are provided for LGBTQI inclusive cancer patient information resources.

Phase 0 Study of Vandetanib-Eluting Radiopaque Embolics as a Preoperative Embolization Treatment in Patients with Resectable Liver Malignancies.

PURPOSE: To assess the safety and tolerability of a vandetanib-eluting radiopaque embolic (BTG-002814) for transarterial chemoembolization (TACE) in patients with resectable liver malignancies. MATERIALS AND METHODS: The VEROnA clinical trial was a first-in-human, phase 0, single-arm, window-of-opportunity study. Eligible patients were aged ≥18 years and had resectable hepatocellular carcinoma (HCC) (Child-Pugh A) or metastatic colorectal cancer (mCRC). Patients received 1 mL of BTG-002814 transarterially (containing 100 mg of vandetanib) 7-21 days prior to surgery. The primary objectives were to establish the safety and tolerability of BTG-002814 and determine the concentrations of vandetanib and the N-desmethyl vandetanib metabolite in the plasma and resected liver after treatment. Biomarker studies included circulating proangiogenic factors, perfusion computed tomography, and dynamic contrast-enhanced magnetic resonance imaging. RESULTS: Eight patients were enrolled: 2 with HCC and 6 with mCRC. There was 1 grade 3 adverse event (AE) before surgery and 18 after surgery; 6 AEs were deemed to be related to BTG-002814. Surgical resection was not delayed. Vandetanib was present in the plasma of all patients 12 days after treatment, with a mean maximum concentration of 24.3 ng/mL (standard deviation ± 13.94 ng/mL), and in resected liver tissue up to 32 days after treatment (441-404,000 ng/g). The median percentage of tumor necrosis was 92.5% (range, 5%-100%). There were no significant changes in perfusion imaging parameters after TACE. CONCLUSIONS: BTG-002814 has an acceptable safety profile in patients before surgery. The presence of vandetanib in the tumor specimens up to 32 days after treatment suggests sustained anticancer activity, while the low vandetanib levels in the plasma suggest minimal release into the systemic circulation. Further evaluation of this TACE combination is warranted in dose-finding and efficacy studies.

Physician Identification Badges: A Multispecialty Quality Improvement Study to Address Professional Misidentification and Bias.

OBJECTIVE: To evaluate whether providing resident physicians with "DOCTOR" role identification badges would impact perceptions of bias in the workforce and alter misidentification rates. PARTICIPANTS AND METHODS: Between October 2019 and December 2019, we surveyed 341 resident physicians in the anesthesiology, dermatology, internal medicine, neurologic surgery, otorhinolaryngology, and urology departments at Mayo Clinic in Rochester, Minnesota, before and after an 8-week intervention of providing "DOCTOR" role identification badges. Differences between paired preintervention and postintervention survey answers were measured, with a focus on the frequency of experiencing perceived bias and role misidentification (significance level, α=.01). Free-text comments were also compared. RESULTS: Of the 159 residents who returned both the before and after surveys (survey response rate, 46.6% [159 of 341]), 128 (80.5%) wore the "DOCTOR" badge. After the intervention, residents who wore the badges were statistically significantly less likely to report role misidentification at least once a week from patients, nonphysician team members, and other physicians (50.8% [65] preintervention vs 10.2% [13] postintervention; 35.9% [46] vs 8.6% [11]; 18.0% [23] vs 3.9% [5], respectively; all P<.001). The 66 female residents reported statistically significantly fewer episodes of gender bias (65.2% [43] vs 31.8% [21]; P<.001). The 13 residents who identified as underrepresented in medicine reported statistically significantly less misidentification from patients (84.6% [11] vs 23.1% [3]; P=.008); although not a statistically significant difference, the 13 residents identifying as underrepresented in medicine also reported less misidentification with nonphysician team members (46.2% [6] vs 15.4% [2]; P=.13). CONCLUSION: Residents reported decreased role misidentification after use of a role identification badge, most prominently improved among women. Decreasing workplace bias is essential in efforts to improve both diversity and inclusion efforts in training programs.

Radiopaque beads loaded with doxorubicin in the treatment of patients with hepatocellular carcinoma: A retrospective, multi-center study.

BACKGROUND AND AIMS: Radiopaque drug-eluting beads are an emerging treatment option for patients with hepatocellular carcinoma (HCC). The primary objective of this study was to evaluate overall disease and target tumor response of non-resectable HCC after TACE with a doxorubicin-loaded radiopaque microsphere. METHODS: Data were abstracted from records of patients with unresectable HCC who received TACE with doxorubicin-loaded radiopaque LC Bead LUMITM microspheres at one of five United States centers between February 2016 - November 2017. Response was measured using modified response criteria in solid tumors. Primary efficacy endpoints included objective response rate (ORR) and disease control rate (DCR) at first assessment post-treatment, both overall and for targeted tumors. ORR was the sum of complete and partial response. DCR was ORR plus stable disease. Toxicity was calculated using common terminology criteria for adverse events. RESULTS: Eighty-two patients were included. Overall ORR and DCR were 47.6% (39/82) and 76.8% (63/82), respectively. ORR and DCR of target tumors were 56% and 98%, respectively. Five patients experienced adverse events (5/82, 6.1%). No grade 4-5 toxicities occurred. CONCLUSIONS: TACE with drug-loaded radiopaque beads is a promising treatment for unresectable HCC. Prospective studies should evaluate whether radiopaque beads reduce off-target distribution of microspheres.

VEROnA Protocol: A Pilot, Open-Label, Single-Arm, Phase 0, Window-of-Opportunity Study of Vandetanib-Eluting Radiopaque Embolic Beads (BTG-002814) in Patients With Resectable Liver Malignancies.

BACKGROUND: Transarterial chemoembolization (TACE) is the current standard of care for patients with intermediate-stage hepatocellular carcinoma (HCC) and is also a treatment option for patients with liver metastases from colorectal cancer. However, TACE is not a curative treatment, and tumor progression occurs in more than half of the patients treated. Despite advances and technical refinements of TACE, including the introduction of drug-eluting beads-TACE, the clinical efficacy of TACE has not been optimized, and improved arterial therapies are required. OBJECTIVE: The primary objectives of the VEROnA study are to evaluate the safety and tolerability of vandetanib-eluting radiopaque embolic beads (BTG-002814) in patients with resectable liver malignancies and to determine concentrations of vandetanib and the N-desmethyl metabolite in plasma and resected liver following treatment with BTG-002814. METHODS: The VEROnA study is a first-in-human, open-label, single-arm, phase 0, window-of-opportunity study of BTG-002814 (containing 100 mg vandetanib) delivered transarterially, 7 to 21 days before surgery in patients with resectable liver malignancies. Eligible patients have a diagnosis of colorectal liver metastases, or HCC (Childs Pugh A), diagnosed histologically or radiologically, and are candidates for liver surgery. All patients are followed up for 28 days following surgery. Secondary objectives of this study are to evaluate the anatomical distribution of BTG-002814 on noncontrast-enhanced imaging, to evaluate histopathological features in the surgical specimen, and to assess changes in blood flow on dynamic contrast-enhanced magnetic resonance imaging following treatment with BTG-002814. Exploratory objectives of this study are to study blood biomarkers with the potential to identify patients likely to respond to treatment and to correlate the distribution of BTG-002814 on imaging with pathology by 3-dimensional modeling. RESULTS: Enrollment for the study was completed in February 2019. Results of a planned interim analysis were reviewed by a safety committee after the first 3 patients completed follow-up. The recommendation of the committee was to continue the study without any changes to the dose or trial design, as there were no significant unexpected toxicities related to BTG-002814. CONCLUSIONS: The VEROnA study is studying the feasibility of administering BTG-002814 to optimize the use of this novel technology as liver-directed therapy for patients with primary and secondary liver cancer. TRIAL REGISTRATION: ClinicalTrial.gov NCT03291379; https://clinicaltrials.gov/ct2/show/NCT03291379. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13696.

Vandetanib-eluting Radiopaque Beads: Pharmacokinetics, Safety, and Efficacy in a Rabbit Model of Liver Cancer.

Background Transarterial chemoembolization with cytotoxic drugs is standard treatment for unresectable intermediate-stage hepatocellular carcinoma but achieves suboptimal outcomes because of hypoxic stress and the production of detrimental proangiogenic factors. An alternative approach using radiopaque embolization beads loaded with the antiangiogenic drug vandetanib may provide improved anticancer efficacy. Purpose To evaluate the pharmacokinetics, safety, and efficacy of vandetanib-eluting radiopaque bead (VERB) chemoembolization of rabbit liver tumors. Materials and Methods Between April 2015 and March 2016, 60 New Zealand white rabbits with VX2 liver tumors were randomly treated with VERBs at different doses, with nonloaded radiopaque beads (ROBs), or with intra-arterial vandetanib suspension (VS) or were not treated. Vandetanib plasma concentration and tumor growth at US were evaluated. Animals were euthanized after 3 days or 3 weeks. Assessment included bead distribution at x-ray imaging and histologic examination, tumor viability at histologic examination, and vandetanib tissue concentration. Group comparison analysis (Mann-Whitney, Kruskal-Wallis, and χ2 tests) and predictive factor analysis for tumor growth and viability were performed. Results Vandetanib plasma concentration was lower with VERBs than with VS (P < .01), while concentration in tumor was higher for VERBs (than for VS) at 3 days (median, 29.2 vs 2.74 ng/mg; P = .48). Tumor growth was lower with VERBs than with ROBs and with VS at both time points, with median values of +114%, +192%, and +466% at 3 weeks, respectively. Tumor viability was lower at 3 days for VERBs than for ROBs and for VS (3%, 18%, and 38%, respectively) but was not significantly different at 3 weeks. The volume of bead in tumor was a significant predictive factor for lower tumor growth in multivariable analysis at 3 days (P = .03). Drug tumor concentration was a significant predictive factor for lower tumor growth at 3 weeks (P = .04). Conclusion Vandetanib-eluting radiopaque bead chemoembolization showed a pharmacokinetic advantage over intra-arterial drug administration in a preclinical model of liver cancer. High deposition of beads and high vandetanib concentration in tumor led to stronger antitumor effects. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Kim and Van den Abbeele in this issue.

Transcatheter chemoembolization in the treatment of HCC in patients not eligible for curative treatments: midterm results of doxorubicin-loaded DC bead.

PURPOSE: To examine the results of segmental transcatheter arterial chemoembolization with doxorubicin-loaded DC Bead in the treatment of hepatocellular carcinoma (HCC) in non-surgical candidates. MATERIAL AND METHODS: Seventy-one patients (60% men; 11% women; mean age 63; range 46-71 years) with documented HCC of 3-10 cm in diameter (mean 6.2) were enrolled prospectively in the study. All patients had cirrhosis-related HCC that was developed on an underlying controlled hepatitis infection. Only patients with compensated cirrhosis--Child A or B--were included in this study. RESULTS: Overall complete response (CR) according to EASL on an intention to treat basis was seen in 11 patients who developed complete necrosis (15.5%). Objective response (OR) ranged from 66.2% to 85.5% across the four treatments. Survival at 12 months was 97.05%. Sustained CR was observed in 11 (16.1%), and OR in 49 (72%). Sustained partial response was seen in 49 patients (72.05%). Survival at 18 months was 94.1%. At 24 months follow-up survival was 91.1%. Sustained OR was seen in 45 patients (66.2%) while sustained CR was 16.1% (11/68). At 30 months survival was 88.2%. One patient with CR developed multifocal HCC in areas that most likely were not embolized during the previous embolization sessions. In this patient recurrence-free survival was 28 months. Alpha Fetroprotein levels decreased significantly in measurements 1 month post each procedure (p < 0.001). Bilirubin, gamma-GT, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase (ALP) showed only transient increases observed during the study period. Severe procedure-related complications were seen in 4.2% (cholecystitis: n = 1; liver abscess: n = 1; pleural effusion: n = 1). Post Embolization Syndrome (PES) was observed in all patients. CONCLUSION: Transcatheter arterial chemoembolization with DC Bead is an effective and safe procedure in the treatment of HCC patients not eligible for curative treatments with high rates of response and high rates of mid term survival.