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

PurposeTo 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 MethodsThe 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.ResultsEight 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.ConclusionsBTG-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.     

Debut y manejo de leucemia mieloblástica aguda durante la gestación: a propósito de un caso

Acute myeloid leukaemia (AML) is one of the deadliest haematological malignancies. During pregnancy it is a rare comorbidity and can lead to adverse outcomes, such as death, without adequate treatment. The management of AML during pregnancy remains a challenge. We report the case of a primigravida 34-year-old, with 18 weeks of amenorrhoea, who attended the emergency department presenting with pain and hypertrophy of the oral mucosa, accompanied by intense asthenia. Acute myeloblastic leukaemia was diagnosed. The possibility of terminating the pregnancy was offered given the lack of evidence regarding the maternal-foetal outcome, but the patient rejected it, so chemotherapy treatment was started. In the ultrasound controls there was no evidence of teratogenic alterations nor foetal growth restriction, and there were no alterations in Doppler flow values. It was decided to end the pregnancy at 32 + 3 GW. A preterm male was born through eutocic delivery with a normal Apgar test and umbilical cord pH, and did not require resuscitation. The puerperium was favourable and 15 days following discharge she was admitted for a bone marrow transplant from her HLA identical sister. The patient died due to rejection of the transplant and the complications derived from this event.     

ImmunoPET imaging of hematological malignancies: From preclinical promise to clinical reality

Immuno-positron emission tomography (immunoPET) imaging is a paradigm-shifting imaging technique for whole-body and all-lesion tumor detection, based on the combined specificity of tumor-targeting vectors [e.g., monoclonal antibodies (mAbs), nanobodies, and bispecific antibodies] and the sensitivity of PET imaging. By noninvasively, comprehensively, and serially revealing heterogeneous tumor antigen expression, immunoPET imaging is gradually improving the theranostic prospects for hematological malignancies. In this review, we summarize the available literature regarding immunoPET in imaging hematological malignancies. We also highlight the pros and cons of current conjugation strategies, and modular chemistry that can be leveraged to develop novel immunoPET probes for hematological malignancies. Lastly, we discuss the use of immunoPET imaging in guiding antibody drug development.     

首荟通便胶囊预防肝胆胰恶性肿瘤化疗后便秘的疗效观察

目的:探讨首荟通便胶囊预防肝胆胰恶性肿瘤化疗后便秘的临床疗效。方法:选取2016年8月至2018年8月河北医科大学第二医院肝胆外科收治的老年肝胆胰恶性肿瘤化疗患者80例作为研究对象,按照随机数字表法随机分为对照组和观察组,每组40例。对照组口服乳果糖口服液,观察组在对照组基础上加服首荟通便胶囊。治疗14 d后,比较2组的临床疗效。结果:中医病症临床疗效观察,对照组总有效率达到75%;观察组,总有效率达到90%,2组比较差异有统计学意义(P<0.05)。临床症状评分观察,对照组总有效率达到77.5%;观察组总有效率达到92.5%,2组比较差异有统计学意义(P<0.05)。排便评分(VAS评分)观察,治疗后对照组排便间隔时间和每次排便时间均长于观察组,2组VAS评分比较,差异均有统计学意义(P<0.05)。结论:首荟通便胶囊可以有效预防肝胆胰恶性肿瘤化疗后的便秘,有效缓解患者排便疼痛程度,减少排便时间,效果显著,值得临床推广。     

Posaconazole therapeutic drug monitoring in clinical practice and longitudinal analysis of the effect of routine laboratory measurements on posaconazole concentrations

Posaconazole is indicated for prophylaxis and treatment of invasive aspergillosis. Therapeutic drug monitoring (TDM) of posaconazole is used to optimise drug exposure. The aim of this study was to analyse and describe the TDM practices and exposure of posaconazole tablets. Patients who received posaconazole for treatment or prophylaxis of fungal infections were included in the study. The following therapeutic window was defined: if concentration was low (<0.7 mg/L for prophylaxis or < 1.5 mg/L for treatment) or high (>3.75 mg/L), the hospital pharmacist provided the physician with dosage advice, which implementation to patient care was analysed. A longitudinal analysis was performed to analyse if different confounding variables had an effect on posaconazole concentrations. Forty‐seven patients were enrolled resulting in 217 posaconazole trough concentrations. A median of 3 (IQR 1‐7) samples was measured per patient. The median concentration was 1.7 mg/L (IQR 0.8‐2.7) for prophylaxis and 1.76 mg/L (IQR 1.3‐2.3) for treatment. Overall, 78 posaconazole concentrations were out of the therapeutic window. For 45 (54%) of these concentrations, a dosage change was recommended. In the longitudinal analysis, the laboratory markers and patient baseline variables did not have an effect on posaconazole concentrations. Adequate posaconazole exposure was shown in 64% (affected 28 patients) of the measured concentrations. TDM practice of posaconazole can be improved by increasing the implementation rate of dose recommendation by a multidisciplinary antifungal stewardship team.     

A case of nodal marginal zone lymphoma with hypersensitivity to mosquito bites as initial symptom

Hypersensitivity to mosquito bites (HMB) refers to skin reactions such as bullae and necrosis, which occurs after being bitten by mosquitoes and can present with multiple systemic reactions such as fever, lymphadenopathy, hepatosplenomegaly simultaneously or subsequently. A 48‐year‐old male patient presented with recurrent erythema, nodules, papules, vesicles and bullae over upper body and bilateral limbs with itching over the sites of mosquito bite for more than 1 year with low‐grade fever and superficial lymph nodes enlargement. The patient's symptoms failed to improve from conventional anti allergic treatment although skin biopsy showed changes of HMB reaction. Subsequently, the lymph node was biopsied and was reported to be nodal marginal zone lymphoma (NMZL), and then the patient was eventually diagnosed with nodal marginal zone lymphoma with HMB. To date only one case of nodal marginal zone lymphoma with HMB has been reported from Korea, and this is the first case to be reported in China.     

Interstitial brachytherapy for gynecologic malignancies: Complications,toxicities, and management

From both a disease and management perspective, locally advanced gynecologic cancers present a significant challenge. Dose escalation with brachytherapy serves as a key treatment, providing conformal radiation while sparing at-risk organs. Intracavitary brachytherapy techniques have been shown to be effective, with improving tumor control and toxicity profiles with the advent of three-dimensional image planning. Despite this, the variations in tumor size, location, and pelvic anatomy may lead to suboptimal dosimetry with standard intracavitary applicators in some clinical scenarios. The addition of interstitial needles (interstitial brachytherapy (interstitial brachytherapy) can improve the conformality of brachytherapy treatments by adding needles to peripheral (and central) regions of the target volume, improving the ability to escalate doses in these undercovered regions while sparing organs at risk. Interstitial brachytherapy can be delivered by intracavitary and interstitial hybrid applicators (ICBT/ISBT), perineal template (P-ISBT), or by free-hand technique. ISBT has however yet to be widely available because of concerns of complications and toxicities from this specialized treatment. However, with the increasing use of three-dimensional image-guided brachytherapy, there is an opportunity to increase the level of expertise in the gynecologic radiation oncology community with an improved understanding of the potential complications and morbidity. In this article, we review the acute and long-term toxicity in both ICBT/ISBT and P-ISBT using image-guided brachytherapy.     

外泌体在血液肿瘤微环境中的作用及其诊治意义

外泌体是细胞外囊泡的一类主要成分，是正常生理情况下组织细胞间信号传递的重要介质；在多种血液肿瘤研究中发现外泌体是骨髓微环境各成分间相互作用的关键载体，由于其广泛存在并含有特定的核酸、蛋白等分子，外泌体被作为潜在的生物标志物和治疗靶点/载体，在血液肿瘤诊治中的重要性近年正逐步受到关注。     

Lenalidomide in the management of eosinophilic dermatosis of hematological malignancy

Eosinophilic dermatosis of hematological malignancy is a paraneoplastic skin eruption associated with chronic lymphocytic leukemia and other B‐cell malignancies. It clinically resembles an insect bite reaction and it can precede the symptoms of the hematological malignancy or be related to a more aggressive course. Different treatments have been proposed, but partial response and recurrence are frequent. Herein, we describe a case of eosinophilic dermatosis associated with mantle cell lymphoma with remission after lenalidomide therapy.