Treatment of Hepatocellular Carcinoma by Multimodal In Situ Vaccination Using Cryoablation and a Plant Virus Immunostimulant.

PURPOSE: To test the hypothesis that cryoablation combined with intratumoral immunomodulating nanoparticles from cowpea mosaic virus (CPMV) as an in situ vaccination approach induces systemic antitumoral immunity in a murine model of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Mice with bilateral, subcutaneous RIL-175 cell-derived HCCs were randomized to 4 groups: (a) phosphate-buffered saline (control), (b) cryoablation only (Cryo), (c) CPMV-treated only (CPMV), and (d) cryoablation plus CPMV-treated (Cryo + CPMV) (N = 11-14 per group). Intratumoral CPMV was administered every 3 days for 4 doses, with cryoablation performed on the third day. Contralateral tumors were monitored. Tumor growth and systemic chemokine/cytokine levels were measured. A subset of tumors and spleens were harvested for immunohistochemistry (IHC) and flow cytometry. One- or 2-way analysis of variance was performed for statistical comparisons. A P value of <.05 was used as the threshold for statistical significance. RESULTS: At 2 weeks after treatment, the Cryo and CPMV groups, alone or combined, outperformed the control group in the treated tumor; however, the Cryo + CPMV group showed the strongest reduction and lowest variance (1.6-fold ± 0.9 vs 6.3-fold ± 0.5, P < .0001). For the untreated tumor, only Cryo + CPMV significantly reduced tumor growth compared with control (9.2-fold ± 0.9 vs 17.8-fold ± 2.1, P = .01). The Cryo + CPMV group exhibited a transient increase in interleukin-10 and persistently decreased CXCL1. Flow cytometry revealed natural killer cell enrichment in the untreated tumor and increased PD-1 expression in the spleen. Tumor-infiltrating lymphocytes increased in Cryo + CPMV-treated tumors by IHC. CONCLUSIONS: Cryoablation and intratumoral CPMV, alone or combined, demonstrated potent efficacy against treated HCC tumors; however, only cryoablation combined with CPMV slowed the growth of untreated tumors, consistent with an abscopal effect.

Imaging Biomarkers and Liquid Biopsy in Assessment of Cervical Cancer.

ABSTRACT: The role of imaging has been increasing in pretherapy planning and response assessment in cervical cancer, particularly in high-resource settings that provide access to computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). In 2018, imaging was incorporated into the International Federation of Gynecology and Obstetrics staging system for cervical cancer. Magnetic resonance imaging is advantageous over CT for evaluation of the primary cervical cancer size and extent, because of superior contrast resolution. Furthermore, quantitative methods, including diffusion-weighted and dynamic contrast-enhanced MRI, show promise in improving treatment response and prognosis evaluation. Molecular imaging with fluorodeoxyglucose-PET/CT and PET/MRI can be particularly helpful in the detection of nodal disease and distant metastases. Semiautomated delineation of 3-dimensional tumor regions of interest has facilitated the development of novel PET-derived biomarkers that include metabolic volume and radiomics textural analysis features for prediction of outcomes. However, posttreatment inflammatory changes can be a confounder and lymph node evaluation is challenging, even with the use of PET/CT. Liquid biopsy has emerged as a promising tool that may be able to overcome some of the drawbacks inherent with imaging, such as limited ability to detect microscopic metastases or to distinguish between postchemoradiotherapy changes and residual tumor. Preliminary evidence suggests that liquid biopsy may be able to identify cervical cancer treatment response and resistance earlier than traditional methods. Future work should prioritize how to best synergize imaging and liquid biopsy as an integrated approach for optimal cervical cancer management.

Identifying enhancement-based staging markers on baseline MRI in patients with colorectal cancer liver metastases undergoing intra-arterial tumor therapy.

OBJECTIVES: To determine if three-dimensional whole liver and baseline tumor enhancement features on MRI can serve as staging biomarkers and help predict survival of patients with colorectal cancer liver metastases (CRCLM) more accurately than one-dimensional and non-enhancement-based features. METHODS: This retrospective study included 88 patients with CRCLM, treated with transarterial chemoembolization or Y90 transarterial radioembolization between 2001 and 2014. Semi-automated segmentations of up to three dominant lesions were performed on pre-treatment MRI to calculate total tumor volume (TTV) and total liver volumes (TLV). Quantitative 3D analysis was performed to calculate enhancing tumor volume (ETV), enhancing tumor burden (ETB, calculated as ETV/TLV), enhancing liver volume (ELV), and enhancing liver burden (ELB, calculated as ELV/TLV). Overall and enhancing tumor diameters were also measured. A modified Kaplan-Meier method was used to determine appropriate cutoff values for each metric. The predictive value of each parameter was assessed by Kaplan-Meier survival curves and univariable and multivariable cox proportional hazard models. RESULTS: All methods except whole liver (ELB, ELV) and one-dimensional/non-enhancement-based methods were independent predictors of survival. Multivariable analysis showed a HR of 2.1 (95% CI 1.3-3.4, p = 0.004) for enhancing tumor diameter, HR 1.7 (95% CI 1.1-2.8, p = 0.04) for TTV, HR 2.3 (95% CI 1.4-3.9, p < 0.001) for ETV, and HR 2.4 (95% CI 1.4-4.0, p = 0.001) for ETB. CONCLUSIONS: Tumor enhancement of CRCLM on baseline MRI is strongly associated with patient survival after intra-arterial therapy, suggesting that enhancing tumor volume and enhancing tumor burden are better prognostic indicators than non-enhancement-based and one-dimensional-based markers. KEY POINTS: • Tumor enhancement of colorectal cancer liver metastases on MRI prior to treatment with intra-arterial therapies is strongly associated with patient survival. • Three-dimensional, enhancement-based imaging biomarkers such as enhancing tumor volume and enhancing tumor burden may serve as the basis of a novel prognostic staging system for patients with liver-dominant colorectal cancer metastases.

Irinotecan-Eluting 75-150-µm Embolics Lobar Chemoembolization in Patients with Colorectal Cancer Liver Metastases: A Prospective Single-Center Phase I Study.

PURPOSE: The primary end point of this trial was to determine the feasibility and safety of transarterial chemoembolization with the use of 75-150-µm drug-eluting embolics loaded with irinotecan (DEE-IRI) for the treatment of metastatic colorectal cancer (CRC) refractory to systemic chemotherapy. MATERIALS AND METHODS: Fourteen patients (mean age 57.9 years) with liver-dominant metastatic disease (14.3% unilobar, 85.7% bilobar), who had failed at least 1 line of chemotherapy, were enrolled and received up to 4 (mean 2.3) cycles of DEE-IRI lobar transarterial chemoembolization. Technical complications and adverse events were recorded, and response was assessed by means of imaging-based criteria. Levels of irinotecan and angiogenesis biomarkers in the serum were measured at multiple time points. RESULTS: Thirty-two DEE-IRI transarterial chemoembolizations were successfully performed, and the full dose (100 mg) was delivered in all cases. The only grade 3-4 toxicity was abdominal pain (29%). One patient had objective response according to the Response Evaluation Criteria in Solid Tumors and World Health Organization, and 3 patients had objective response according to the European Association for the Study of the Liver. The median overall survival was 18.14 months, and the 1-year survival was 65%. The average plasma Cmax of the active metabolite was 41.5 ± 26.1 ng/mL, with average Tmax of 1.3 ± 0.5 hours. The treatment significantly reduced levels of vascular endothelial growth factor receptor 1 (VEGFR1) at 24 hours. CONCLUSIONS: Lobar transarterial chemoembolization with the use of DEE-IRI is a technically feasible and well tolerated palliative treatment for patients with refractory liver-predominant CRC metastatic disease and has acceptable pharmacokinetics. VEGFR1 is a potential biomarker for predicting treatment efficacy and risk of adverse events.

Assessment of an Innovative Voluntary Substance Abuse Treatment Program Designed to Replace Compulsory Drug Detention Centers in Malaysia.

BACKGROUND: As part of an ongoing initiative by the Malaysian government to implement alternative approaches to involuntary detention of people who use drugs, the National Anti-Drug Agency has created new voluntary drug treatment programs known as Cure and Care (C&C) Centers that provide free access to addiction treatment services, including methadone maintenance therapy, integrated with social and health services. OBJECTIVES: We evaluated early treatment outcomes and client satisfaction among patients accessing C&C treatment and ancillary services at Malaysia's second C&C Center located in Kota Bharu, Kelantan. METHODS: In June-July 2012, a cross-sectional convenience survey of 96 C&C inpatients and outpatients who entered treatment >30 days previously was conducted to assess drug use, criminal justice experience, medical co-morbidities, motivation for seeking treatment, and attitudes towards the C&C. Drug use was compared for the 30-day-period before C&C entry and the 30-day-period before the interview. RESULTS: Self-reported drug use levels decreased significantly among both inpatient and outpatient clients after enrolling in C&C treatment. Higher levels of past drug use, lower levels of social support, and more severe mental health issues were reported by participants who were previously imprisoned. Self-reported satisfaction with C&C treatment services was high. Conclusions/Importance: Preliminary evidence of reduced drug use and high levels of client satisfaction among C&C clients provide support for Malaysia's ongoing transition from compulsory drug detention centers (CDDCs) to these voluntary drug treatment centers. If C&C centers are successful, Malaysia plans to gradually transition away from CDDCs entirely.

Pretreatment drug use characteristics and experiences among patients in a voluntary substance abuse treatment center in Malaysia: A mixed-methods approach.

BACKGROUND: Drug use in Malaysia remains a significant public health and social problem despite implementation of harsh punitive drug policies such as forcibly placing suspected drug users into compulsory drug detention centers (CDDCs). Following criticism over human right violations in CDDCs, Malaysia has begun to transition towards voluntary drug treatment centers known as Cure & Care (C&C) centers. To best serve the needs of regional C&C centers, data on drug use are essential among patients accessing treatment. Using a mixed-methods approach, the authors examined pretreatment drug use characteristics and experiences with addiction treatment among C&C patients in Kelantan-a religiously conservative state in northeast Malaysia with high prevalence of drug use but where limited data are available on drug use patterns. METHODS: A mixed-methods study utilizing surveys (n = 96) and semistructured interviews (n = 20) was conducted among a convenience sample of inpatients and outpatients at the Pengkalan Chepa C&C Center in Kelantan. RESULTS: Survey results showed that 89.6% of participants met screening criteria for moderate to severe addiction severity. Nearly 90% reported lifetime illicit amphetamine (syabu, meth, ice, and pil kuda) use, followed by alcohol (60.4%) and opioids (52.1%). Qualitative results pointed to the powerful influence of peer networks in drug initiation and relapse, and the positive effect of the C&C center on drug rehabilitation. CONCLUSIONS: The drug use profile of the Kelantan C&C center enrollees shows extensive pretreatment amphetamine use, polysubstance use, and injection drug use, including high-risk behaviors such as sharing needles, syringes, and containers. Evidence points to the need for integration of social support-oriented practices and behavioral interventions into the rehabilitation of drug users in this region.

Interdisciplinary Approach to Expedited Outpatient Gastrostomy Tube Placement in Head and Neck Cancer Patients: A Single Center Retrospective Study.

RATIONALE AND OBJECTIVE: Treatment for head and neck cancer (HNC) can lead to decreased oral intake which often requires gastrostomy tube (g-tube) placement to provide nutritional support. A multidisciplinary team (MDT) consisting of interventional radiology (IR), HNC oncology and surgery, nutrition, and speech language pathology departments implemented an expedited outpatient g-tube placement pathway to reduce hospital stays and associated costs, initiate feeds sooner, and improve communication between care teams. This single center study investigates differences in complications, time to procedure and costs savings with implementing this pathway. METHODS: 142 patients with HNC who underwent elective image guided g-tube placement by IR from 2015 to 2022 were identified retrospectively. 52 patients underwent the traditional pathway, and 90 patients underwent the expedited pathway. Patient demographics, procedure characteristics, periprocedural costs and 90-day complication rates were collected and compared statistically. RESULTS: The 90-day complication rate was comparable between groups (traditional=32.7%; expedited=22.2%; p-value=0.17). The expedited pathway decreased the time from consult to procedure by 11.1 days (95% CI 7.6 - 14.6; p < 0.001) and decreased charge per procedure by $2940 (95% CI $989-$4891; p < 0.001). CONCLUSION: A MDT for the treatment of patients with HNC successfully provided enteral nutrition support faster, with fewer associated costs, and in a more patient centered approach than previously done at this institution.

Getting PrEPared for HIV Prevention Navigation: Young Black Gay Men Talk About HIV Prevention in the Biomedical Era.

Biomedical HIV prevention strategies, such as pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP), represent new opportunities to reduce critically high HIV infection rates among young black men who have sex with men (YBMSM). We report results of 24 dyadic qualitative interviews (N=48), conducted in Los Angeles, CA, exploring how YBMSM and their friends view PrEP and PEP. Interviews were analyzed using a grounded theory approach. Participants had widely divergent levels of knowledge about these prevention methods. Misconceptions and mistrust regarding PrEP were common, and concerns were expressed about PrEP-related stigma and the potential for gossip among peers who might assume a person on PrEP was HIV-positive. Yet participants also framed PrEP and PEP as valuable new options within an expanded "tool kit" of HIV prevention strategies that created possibilities for preventing new HIV infections, dating men with a different HIV status, and decreased anxiety about exposure to HIV. We organized themes around four main areas: (1) information and misinformation about biomedical HIV prevention; (2) expectations about PrEP, sexual behavior, and stigma; (3) gossip, disclosure, and "spreading the word" about PrEP and PEP; and (4) the roles of PrEP and PEP in an expanded HIV prevention tool kit. The findings suggest a need for guidance in navigating the increasingly complex array of HIV-prevention options available to YBMSM. Such "prevention navigation" could counter misconceptions and address barriers, such as stigma and mistrust, while helping YBMSM make informed selections from among expanded HIV prevention options.

An exploratory qualitative assessment of self-reported treatment outcomes and satisfaction among patients accessing an innovative voluntary drug treatment centre in Malaysia.

BACKGROUND: In Malaysia, compulsory drug detention centres (CDDCs) hold suspected drug users for two years without adjudication. Acute detoxification without healthcare access has been documented. CDDCs are criticized globally due to ineffectiveness in treating addiction and human rights violations. In response, the Malaysian government began transitioning these facilities into voluntary drug treatment centres known as "Cure and Care" (C&C) centres that embrace a holistic treatment-based approach to drug addiction rehabilitation. METHODS: An explorative qualitative study was undertaken to explore patient perspectives and satisfaction regarding treatment and services at the new Cure and Care centre in Kota Bharu, Malaysia. A convenience sample of 20 patients was recruited to participate in semi-structured in-depth interviews. Content analysis was used to identify the salient themes. RESULTS: Patients identified methadone treatment, psychosocial programs, religious instruction, and recreational activities as important factors contributing to treatment success for addressing both health and addiction needs. Though many had previously been in a CDDC, adherence to treatment in the C&C centre was perceived to be facilitated by the degree of social support, the voluntary nature and the array of new programs available for selection. CONCLUSION: C&Cs represents a dramatic shift in the Malaysian government's approach to drug addiction. Our findings demonstrate positive patient experiences associated with the holistic treatment-based approach of these centres. This exploratory study provides additional evidence to document this ongoing policy transition and may guide continued expansion of new holistic drug treatment programs across the country.