Hypo-Vascular Liver Metastases Treated with Transarterial chemoembolization: Assessment of Early Response by Volumetric Contrast-Enhanced and Diffusion-Weighted Magnetic Resonance Imaging

OBJECTIVE: To evaluate the value of anatomic and volumetric functional magnetic resonance imaging (MRI) in early assessment of response to trans-arterial chemoembolization (TACE) in hypovascular liver metastases. METHODS: This retrospective study included 52 metastatic lesions (42 targeted and 10 non-targeted) in 17 patients who underwent MRI before and early after TACE. Two reviewers reported response by anatomic criteria (Response Evaluation Criteria in Solid Tumor [RECIST], modified RECIST [mRECIST], and European Association for the Study of Liver Disease [EASL]) and functional criteria (volumetric apparent diffusion coefficient and contrast enhancement). Treatment endpoint was RECIST at 6 months. A 2-sample paired t test was used to compare the mean changes after intra-arterial therapy. P < .05 was considered statistically significant. RESULTS: Reduction in mRECIST and EASL at 1 month was significant in the whole cohort as well as in responders by RECIST at 6 months, and the changes fulfilled partial response criteria for both metrics in responders. Responders also had significant changes in volumetric apparent diffusion coefficient (P = .01 and P = .03) and contrast enhancement (P < .0001 and P < .0001) at 1 month for both readers, respectively. CONCLUSION: At 1 month post treatment, responders did not fulfill RECIST criteria but fulfilled mRECIST and EASL criteria. In addition, volumetric contrast-enhanced and diffusion-weighted MRI may be helpful in evaluating early treatment response after TACE in hypovascular liver metastases in patients who have failed to respond to initial chemotherapy.     

Renal Cell Carcinoma Metastatic to the Liver: Early Response Assessment after Intraarterial Therapy Using 3D Quantitative Tumor Enhancement Analysis

PURPOSELiver metastases from renal cell carcinoma (RCC) are not uncommon in the course of disease. However, data about tumor response to intraarterial therapy (IAT) are scarce. This study assessed whether changes of enhancing tumor volume using quantitative European Association for the Study of the Liver (qEASL) on magnetic resonance imaging (MRI) and computed tomography (CT) can evaluate tumor response and predict overall survival (OS) early after therapy.RESULTSMean qEASL (cm³) decreased from 93.5 to 67.2 cm³ (P= .004) and mean qEASL (%) from 63.1% to 35.6% (P= .001). No significant changes were observed using other response criteria. qEASL was the only significant predictor of OS when used to stratify patients into responders and nonresponders with median OS of 31.9 versus 11.1 months (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.19-0.97; P= .042) for qEASL (cm³) and 29.9 versus 10.2 months (HR, 0.09; 95% CI, 0.01-0.74; P= .025) for qEASL (%).CONCLUSIONThree-dimensional (3D) quantitative tumor analysis is a reliable predictor of OS when assessing treatment response after IAT in patients with RCC metastatic to the liver. qEASL outperforms conventional non-3D methods and can be used as a surrogate marker for OS early after therapy.     

Identifying the Association of Contrast Enhancement with Vascular Endothelia Growth Factor Expression in Anaplastic Gliomas: A Volumetric Magnetic Resonance Imaging Analysis

Contrast enhancement is a crucial radiologic feature of malignant brain tumors, which are associated with genetic changes of the tumor. The purpose of the current study was to investigate the potential relationship among tumor contrast enhancement with MR imaging, vascular endothelial growth factor (VEGF) expression, and survival outcome in anaplastic gliomas. MR images from 240 patients with histologically confirmed anaplastic gliomas were retrospectively analyzed. The volumes of T2 hyperintense, contrast enhanced regions and necrotic regions on postcontrast T1-weighted images were measured. The ratio of the enhanced volume to necrotic volume was compared between patients with high versus low levels of VEGF expression and was further used in the survival analysis. The volumetric ratio of enhancement to necrosis was significantly higher in patients with low VEGF expression than in those with high VEGF expression (Mann-Whitney, p = 0.009). In addition, the enhancement/necrosis ratio was identified as a significant predictor of progression-free survival (Cox regression model, p = 0.004) and overall survival (Cox regression model, p = 0.006) in the multivariate analysis. These results suggest that the volumetric ratio of enhancement to necrosis could serve as a noninvasive radiographic marker associated with VEGF expression and that this ratio is an independent predictor for progression-free survival and overall survival in patients with anaplastic gliomas.     

肝动脉导管化疗栓塞序贯经皮微波消融治疗原发性肝癌的临床应用

目的:探讨肝动脉导管化疗栓塞(TACE)序贯B超/CT精准引导下经皮微波消融(MWA)在原发性肝癌中的治疗应用,分析比较疗效。方法:回顾性分析2016年1月至2018年7月在上海交通大学附属第一人民医院接受治疗的96例原发性肝癌患者,42例行TACE序贯联合B超/CT精准引导下MWA治疗(联合组),另54例仅行单纯TACE治疗(TACE组)。术后1月、3月、6月、1年、2年复查增强CT/MRI、AFP、肝功能,随访2年比较两组患者肿瘤坏死、复发、进展和生存情况,评价两组疗效。结果:联合组肿瘤坏死率92.9%,TACE组肿瘤坏死率48.1%,差异有统计学意义(P0.05);联合组肿瘤复发率7.1%,TACE组肿瘤复发率24.1%,差异有统计学意义(P0.05);联合组肿瘤进展率19.1%,TACE组肿瘤进展率27.8%,差异无统计学意义(P0.05);联合组肿瘤进展时间13.2个月,TACE组肿瘤进展时间7.6个月,差异有统计学差异(P0.05);联合组1年生存率83.3%,TACE组1年生存率57.4%,差异有统计学意义(P0.05);联合组2年生存率62%,TACE组2年生存率31.5%,差异有统计学意义(P0.05);联合组中位生存时间28.9个月,TACE组中位生存时间16.9个月,差异有统计学意义(P0.05)。结论:TACE序贯MWA治疗肝癌安全有效,互补增益,是肝癌综合治疗的新模式。     

Multidetector Computed Tomography-Based Microstructural Analysis Reveals Reduced Bone Mineral Content and Trabecular Bone Changes in the Lumbar Spine after Transarterial Chemoembolization Therapy for Hepatocellular Carcinoma

Purpose

It is well recognized that therapeutic irradiation can result in bone damage. However, long-term bone toxicity associated with computed tomography (CT) performed during interventional angiography has received little attention. The purpose of this study was to determine the prevalence of osteoporosis and trabecular microstructural changes in patients after transarterial chemoembolization (TACE) for hepatocellular carcinoma therapy using an interventional-CT system.

Materials and Methods

Spinal microarchitecture was examined by 64-detector CT in 81 patients who underwent TACE, 35 patients with chronic hepatitis, and 79 controls. For each patient, the volumetric CT dose index (CTDIv) during TACE (CTDIv (TACE)), the dose-length product (DLP) during TACE (DLP (TACE)), and CTDIv and DLP of routine dynamic CT scans (CTDIv (CT) and DLP (CT), respectively), were calculated as the sum since 2008. Using a three dimensional (3D) image analysis system, the tissue bone mineral density (tBMD) and trabecular parameters of the 12th thoracic vertebra were calculated. Using tBMD at a reported cutoff value of 68 mg/cm³, the prevalence of osteoporosis was assessed.

Results

The prevalence of osteoporosis was significantly greater in the TACE vs. the control group (39.6% vs. 18.2% for males, P<0.05 and 60.6% vs. 34.8% for females, P<0.01). Multivariate regression analysis demonstrated that sex, age, and CTDIv (CT) significantly affected the risk of osteoporosis. Of these indices, CTDIv (CT) had the highest area under the curve (AUC) (0.735). Correlation analyses of tBMD with cumulative radiation dose revealed weak correlations between tBMD and CTDIv (CT) (r ² = 0.194, P<0.001).

Conclusion

The prevalence of osteoporosis was significantly higher in post TACE patients than in control subjects. The cumulative radiation dose related to routine dynamic CT studies was a significant contributor to the prevalence of osteoporosis.     

Fuzheng Jiedu Xiaoji formulation inhibits hepatocellular carcinoma progression in patients by targeting the AKT/CyclinD1/p21/p27 pathway

BackgroundHepatocellular carcinoma (HCC) is a common malignant tumor with limited treatment options. Conventional antitumor therapy combined with traditional Chinese medicine (TCM) to limit tumor progression has gradually become the focus of complementary and alternative therapies for HCC treatment. The Fuzheng Jiedu Xiaoji formulation (FZJDXJ) alleviates the clinical symptoms of patients and inhibits tumor progression, but its curative effect still requires extensive clinical research and mechanistic analysis.PurposeTo explore the effectiveness of FZJDXJ in HCC patients and investigate its biological function and mechanism underlying anticancer therapy.MethodsThis randomized controlled clinical trial enrolled 291 HCC patients receiving transcatheter arterial chemoembolization (TACE) therapy; patients received either FZJDXJ combined with standard treatment, or standard treatment alone, for 48 weeks. Statistical analyses were performed according to survival time at the end of the trial. The main constituents of the FZJDXJ extracts were identified and evaluated using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and molecular docking. The antitumor effects of FZJDXJ and its specific biological mechanism of action were studied.ResultsAfter 48 weeks of treatment, one-year overall survival (OS) and progression-free survival (PFS) were significantly different between the two groups. Co-administration of FZJDXJ and TACE prolonged the OS of HCC patients, especially in BCLC A or B stage. FZJDXJ and TACE treatment effectively extended the PFS of patients, especially in the BCLC B stage. HPLC-MS/MS identified 1619 active constituents of FZJDXJ, including formononetin, chlorogenic acid (CGA), caffeic acid, luteolin, gallic acid, diosgenin, ergosterol endoperoxide, and lupeol, which may function through the AKT/CyclinD1/p21/p27 pathways. Through molecular docking, CGA and gallic acid could effectively combine with Thr308, an important phosphorylation site of AKT1. FZJDXJ inhibited tumor growth in nude mice. In vitro, FZJDXJ-mediated serum inhibited the proliferation, migration, and invasion of liver cancer cells, and promoted cell apoptosis.ConclusionClinically, FZJDXJ combined with TACE therapy significantly prolonged OS and PFS and reduced the mortality rate of HCC patients. Mechanistically, FZJDXJ effectively inhibited the proliferation and migration of liver cancer cells through the modulation of the AKT/CyclinD1/p21/p27 pathways, and may be a promising TCM drug for anti-HCC therapy.     

Optimal timing of combining sorafenib with trans-arterial chemoembolization in patients with hepatocellular carcinoma: A meta-analysis

BackgroundThe combination therapy of trans-arterial chemoembolization (TACE) and sorafenib were proved to be one of the effective methods for intermediate and advanced hepatocellular carcinoma (HCC). Although it has been confirmed that the combination therapy can prolong survival for advanced HCC effectively, the therapeutic efficacy and safety are still controversial and the clinical value has not been determined. This meta-analysis aims to evaluate the efficacy and safety of combination therapy and discuss the optimal timing of combination for better clinical benefits.Data sourcesPubMed, EMBASE, the Cochrane Library, MEDLINE, and Web of Science were systematically reviewed to search for relevant studies published before May 15, 2021. Studies comparing the efficacy and safety of TACE + sorafenib with TACE + placebo / alone were adopted. Two reviewers independently extracted study outcomes. The data were analyzed through fixed/random-effect meta-analysis models with Review Manager (Version 5. 3) software.Results7 randomized controlled trials (RCTs) were included with 1464 patients with unresectable HCC (734 in TACE + sorafenib group and 730 in TACE + placebo or alone group). Meta-analysis showed that objective response rate (ORR) and disease control rate (DCR) were slightly improved in TACE + sorafenib group (ORR: risk ratio = 1.24; 95% confidence interval: 1.08–1.42; P = 0.002; DCR: risk ratio = 1.09; 95% confidence interval: 1.01–1.18; P = 0.02). The combination therapy obviously improved time to progression (TTP) (hazard ratio: 0.73; 95% confidence interval: 0.55–0.96; P = 0.03) and progression-free survival (PFS) (hazard ratio 0.62; 95% confidence interval: 0.52–0.73, P < 0.00001) but not overall survival (OS) (hazard ratio: 0.93; 95% confidence interval: 0.59–1.46; P = 0.75) or time to untreatable progression (TTUP) (hazard ratio: 0.76; 95% confidence interval: 0.31–1.89; P = 0.56). In addition, the incidence of adverse reactions (AEs) in combination group were higher than TACE + placebo / alone group. Furthermore, the subgroup analysis showed that the heterogeneity of TTP was notably decreased (pre-TACE: P = 0.12, I² = 48%; post-TACE: P = 0.58, I² = 0%), and the hazard ratio was 0.59 (95% confidence interval: 0.51–0.68; P < 0.00001) in pre-TACE subgroup which indicated that combination before TACE significantly prolonged TTP but not in combination after TACE (hazard ratio: 0.88; 95% confidence interval: 0.62–1.24; P = 0.46). In term of AEs, sensitivity analysis indicated that the risk ratio for hand-foot skin reaction, diarrhea, rash/desquamation, and hypertension was 7.41, 2.58, 2.14, 1.55 in pre-TACE subgroup respectively and was 11.34, 3.26, 3.61, 4.11 in post-TACE subgroup respectively (All P < 0.05).ConclusionThe combination of TACE and sorafenib significantly can improve TTP and PFS, and reduce the level of risk of adverse reactions of unresectable HCC, especially in the combination before TACE.     

肝动脉灌注化疗栓塞联合射频消融对中晚期肝癌患者生存率、肝功能和T淋巴细胞亚群的影响

摘要 目的：探讨肝动脉灌注化疗栓塞（TACE）联合射频消融（RFA）对中晚期肝癌患者生存率、肝功能和T淋巴细胞亚群的影响。方法：选取2014年7月~2018年4月期间我院收治的中晚期肝癌患者126例,根据随机数字表法将患者分为对照组和研究组,各63例。对照组给予TACE治疗,研究组则在对照组的基础上联合RFA治疗,比较两组患者疗效、生存率、肝功能、T淋巴细胞亚群及不良反应情况。结果：研究组治疗后临床总有效率为69.84%（44/63）,显著高于对照组患者的50.79%（32/63）（P<0.05）。两组患者治疗后丙氨酸氨基转移酶（ALT）、总胆红素（TBIL）、天门冬氨酸氨基转移酶（AST）均较治疗前降低,且研究组低于对照组（P<0.05）。两组治疗后CD4⁺、CD4⁺/CD8⁺较治疗前降低,但研究组高于对照组（P<0.05）;CD8⁺较治疗前升高,但研究组低于对照组（P<0.05）。两组不良反应发生率比较差异无统计学意义（P>0.05）。研究组患者1年、2年生存率均高于对照组（P<0.05）。结论：TACE联合RFA治疗中晚期肝癌患者,安全性较好,疗效较好,可有效改善患者肝功能,减轻机体免疫抑制,提高患者生存率。     

不同方式治疗原发性肝癌合并门静脉癌栓的治疗效果比较

目的:对不同方式治疗原发性肝癌(HCC)合并门静脉癌栓(PVTT)的治疗效果进行比较。方法:收取我院2010年2月至2013年3月收治的HCC合并PVTT患者83例进行回顾性分析,按照治疗方法的不同分为A组(手术+经导管动脉化疗栓塞TACE)26例、B组(手术+门静脉化疗PVC)25例以及C组(手术+TACE+PVC)32例。对三组患者不良反应发生情况、生存率、生存质量进行考察与比较,并对可能影响生存率的因素进行分析。结果:三组患者均行手术切除,切除率为100%。三组患者化疗后不良反应发生率方面比较差异无统计学意义(P0.05)。C组患者生存质量提高总有效率及改善率分别为78.13%和50.00%,均显著高于其他两组,差异有统计学意义(P0.05)。C组患者中位生存时间及半年、1年、2年、3年生存率均显著高于A组和B组,差异具有统计学意义(P0.05)。影响HCC合并PVTT患者的主要因素包括肿瘤大小、肿瘤数目、病理分级及癌栓类型(P0.05)。结论:HCC合并PVTT患者术后使用TACE+PVC联合治疗可有效提高患者生存率,改善生活质量。     

Clinical Characteristics of 582 Patients with Uveal Melanoma in China

Objective

To assess clinical characteristics, treatment and survival of patients with uveal melanoma in China.

Methods

The retrospective study included all patients with malignant uveal melanoma who were consecutively examined in the study period from January 2005 and June 2015 in the Beijing Tongren hospital.

Results

The mean age of the 582 patients (295(50.7%) women) was 44.6±12.6 years (range:5–77 years). The tumors were located most often in the superior temporal region (in 117(21.5%) patients) and least common in the inferior region (in 31(5.7%) patients). In 548(94.2%) patients, the tumors were located in the choroid, in 33(5.7%) patients in the ciliary body, and in one (0.2%) patient in the iris. Treatment included episcleral brachytherapy (415(71.3%) patients), local tumor resection (48(8.2%) patients) and primary enucleation (119(20.4%) patients). In 53 individuals out of the 415 patients with primary brachytherapy, episcleral brachytherapy was followed by enucleation, due to an increasing tumor size or due to uncontrolled neovascular glaucoma. Median follow-up time was of 30 months (range: 1–124 months; mean: 34.8 ± 24.4 months). Overall survival rate at 5 and 10 years was of 92.7% and 85.1%. Younger age (P = 0.017), tumor location in the nasal meridian(P = 0.004), smaller tumor size (P<0.001), hemispheric tumor shape (P = 0.025), histological tumor cell type (spindle-cell type versus epitheloid cell type;P = 0.014), and type of treatment (episcleral brachytherapy versus local tumor resection and versus primary enucleation; P<0.001) were significantly associated with the overall survival in univariate analysis, while in multivariate analysis only smaller tumor size was significantly (P<0.001; RR: 4.75; 95% confidence interval:2.11,10.7) associated with better overall survival.

Conclusions

In this study on clinical characteristics of uveal melanoma of a larger group of patients from China, the onset age was considerably younger and survival rate better than in studies from Western countries. Tumor size was the most significant factor for survival.     

Optimal timing of combining sorafenib with trans-arterial chemoembolization in patients with hepatocellular carcinoma: A meta-analysis

BackgroundThe combination therapy of trans-arterial chemoembolization (TACE) and sorafenib were proved to be one of the effective methods for intermediate and advanced hepatocellular carcinoma (HCC). Although it has been confirmed that the combination therapy can prolong survival for advanced HCC effectively, the therapeutic efficacy and safety are still controversial and the clinical value has not been determined. This meta-analysis aims to evaluate the efficacy and safety of combination therapy and discuss the optimal timing of combination for better clinical benefits.Data sourcesPubMed, EMBASE, the Cochrane Library, MEDLINE, and Web of Science were systematically reviewed to search for relevant studies published before May 15, 2021. Studies comparing the efficacy and safety of TACE + sorafenib with TACE + placebo / alone were adopted. Two reviewers independently extracted study outcomes. The data were analyzed through fixed/random-effect meta-analysis models with Review Manager (Version 5. 3) software.Results7 randomized controlled trials (RCTs) were included with 1464 patients with unresectable HCC (734 in TACE + sorafenib group and 730 in TACE + placebo or alone group). Meta-analysis showed that objective response rate (ORR) and disease control rate (DCR) were slightly improved in TACE + sorafenib group (ORR: risk ratio = 1.24; 95% confidence interval: 1.08–1.42; P = 0.002; DCR: risk ratio = 1.09; 95% confidence interval: 1.01–1.18; P = 0.02). The combination therapy obviously improved time to progression (TTP) (hazard ratio: 0.73; 95% confidence interval: 0.55–0.96; P = 0.03) and progression-free survival (PFS) (hazard ratio 0.62; 95% confidence interval: 0.52–0.73, P < 0.00001) but not overall survival (OS) (hazard ratio: 0.93; 95% confidence interval: 0.59–1.46; P = 0.75) or time to untreatable progression (TTUP) (hazard ratio: 0.76; 95% confidence interval: 0.31–1.89; P = 0.56). In addition, the incidence of adverse reactions (AEs) in combination group were higher than TACE + placebo / alone group. Furthermore, the subgroup analysis showed that the heterogeneity of TTP was notably decreased (pre-TACE: P = 0.12, I² = 48%; post-TACE: P = 0.58, I² = 0%), and the hazard ratio was 0.59 (95% confidence interval: 0.51–0.68; P < 0.00001) in pre-TACE subgroup which indicated that combination before TACE significantly prolonged TTP but not in combination after TACE (hazard ratio: 0.88; 95% confidence interval: 0.62–1.24; P = 0.46). In term of AEs, sensitivity analysis indicated that the risk ratio for hand-foot skin reaction, diarrhea, rash/desquamation, and hypertension was 7.41, 2.58, 2.14, 1.55 in pre-TACE subgroup respectively and was 11.34, 3.26, 3.61, 4.11 in post-TACE subgroup respectively (All P < 0.05).ConclusionThe combination of TACE and sorafenib significantly can improve TTP and PFS, and reduce the level of risk of adverse reactions of unresectable HCC, especially in the combination before TACE.     

Effect of the normal liver mean dose on intrahepatic recurrence in patients with hepatocellular carcinoma after receiving liver stereotactic body radiation therapy

Background and purposeThis study aims to evaluate whether dosimetric parameters affect the intrahepatic out-field recurrence or distant metastasis-free survival following the stereotactic body radiation therapy (SBRT) in patients with hepatocellular carcinoma (HCC).Materials and methodsA total of 76 patients with HCC who were treated with SBRT from January 2015 to May 2020 were included in this retrospective study. The main clinical endpoints considered were intrahepatic out-field free survival (OutFFS) and distant metastasis-free survival (DMFS). The target parameters and the liver were documented including tumor diameters, gross tumor volume (GTV), Liver minus GTV volume (LGV), and Liver minus GTV mean dose (LGD). Multivariable Cox regression with forward stepwise selection was performed to identify independent risk factors for OutFFS and DMFS. Maximally selected rank statistics were used to determine the most informative cut-off value for age and LGD.ResultsThe median follow-up was 28.2 months (range, 7.7–74.5 months). LGD higher than 12.54 Gy [HR, 0.861(0.747–0.993); p = 0.040] and age greater than 67-year-old [HR, 0.966(0.937–0.997); p = 0.030] are two independent predictors of OutFFS, previous TACE treatment [HR, 0.117(0.015–0.891); p = 0.038] was an independent predictor of DMFS.ConclusionsThe results of this study suggested that the higher the dose received by the normal liver (greater than 12.54 Gy) the better the intrahepatic out-field recurrence-free survival (RFS) rate. Further study is warranted to confirm and to better understand this phenomenon.     

CT-guided 125I brachytherapy in the treatment of distant metastases in the oral cavity and maxillofacial region

PURPOSE: We aimed to evaluate the feasibility and clinical effectiveness of CT-guided ¹²⁵I brachytherapy for distant oral and maxillofacial metastases. MATERIALS AND METHODS: We retrospectively analyzed 65 patients with 84 distant oral and maxillofacial metastases. Thirty-one patients with 38 lesions received ¹²⁵I brachytherapy (group A) and 34 with 46 lesions received external beam radiotherapy (EBRT; group B). RESULTS: Median follow-up time was 16 months. The 3-, 6-, 12-, 18-, and 24-month local control rates for group A were 83.9%, 75.9%, 66.7%, 38.4%, and 25.0%, respectively; for group B they were 76.5%, 62.5%, 43.8%, 25.0%, and 0.0%, respectively (P < .05); the median local tumor progression-free survival times were 14 and 9 months, respectively. Group A had a better local tumor progression-free survival (LTPFS) relative to group B (P < .001; HR, 6.961 [95%CI, 2.109, 9.356]). Cox proportional hazards regression analysis indicated that ¹²⁵I brachytherapy, tumor size, and primary pathological type were the independent factors affecting LTPFS. Additionally, ¹²⁵I brachytherapy showed better performance in relieving patient clinical symptoms relative to EBRT (P < .05). Group A also had fewer complications than group B, especially regarding grade 3/4 complications according to Radiation Therapy Oncology Group grading criteria. Mean overall survival times in groups A and B were 17.1 and 14.8 months, respectively. CONCLUSION: CT-guided ¹²⁵I brachytherapy is feasible and safe for distant oral and maxillofacial metastases; it achieved a better local control rate, longer LTPFS and fewer complications without compromising overall survival compared with EBRT.     

肝动脉化疗栓塞术联合碘125粒子植入对原发性肝癌合并门静脉癌栓患者血清TSGF、TK-1、sB7-H3水平的影响

摘要 目的：观察肝动脉化疗栓塞术（TACE）联合碘125粒子植入治疗原发性肝癌（PHC）合并门静脉癌栓（PVTT）的疗效及对血清恶性肿瘤特异性生长因子（TSGF）、胸苷激酶1（TK-1）、可溶性B7-H3（sB7-H3）的影响。方法：选择新疆医科大学附属肿瘤医院2019年1月到2020年1月期间收治的PHC合并PVTT患者120例,按照随机数字表法分为对照组（TACE治疗,60例）和联合组（TACE结合碘125粒子植入治疗,60例）。观察两组疗效、肝功能指标[丙氨酸氨基转移酶（ALT）、谷草转氨酶（AST）、总胆红素（TBiL）]、血清肿瘤标志物[甲胎蛋白（AFP）、细胞角蛋白19片段（CYFRA21-1）及癌胚抗原（CEA）]、TSGF、TK-1、sB7-H3。随访3年,采用Kaplan-Meier曲线分析（Log-Rank检验）两组患者总生存期（OS）的差异。结果：联合组的临床总有效率高于对照组（P<0.05）。与治疗前相比,两组治疗后ALT、AST、TBiL均下降,且联合组均低于对照组同期（P<0.05）。与治疗前相比,两组治疗后AFP、CYFRA21-1、CEA均下降,且联合组均低于对照组同期（P<0.05）。与治疗前相比,两组治疗后TSGF、TK-1、sB7-H3均下降,且联合组均低于对照组同期（P<0.05）。联合组的OS长于对照组（P<0.05）。结论：TACE联合碘125粒子植入治疗PHC合并PVTT患者,可提高临床疗效,降低血清肿瘤标志物水平,减轻肝功能损伤,延长患者OS并调节血清TSGF、TK-1、sB7-H3水平。     

Is abdominal compression useful in lung stereotactic body radiation therapy? A 4DCT and dosimetric lobe-dependent study

PurposeTo determine the usefulness of abdominal compression in lung stereotactic body radiation therapy (SBRT) depending on lobe tumor location.Materials and methodsTwenty-seven non-small cell lung cancer patients were immobilized in the Stereotactic Body Frame? (Elekta). Eighteen tumors were located in an upper lobe, one in the middle lobe and nine in a lower lobe (one patient had two lesions). All patients underwent two four-dimensional computed tomography (4DCT) scans, with and without abdominal compression. Three-dimensional tumor motion amplitude was determined using manual landmark annotation. We also determined the internal target volume (ITV) and the influence of abdominal compression on lung dose-volume histograms.ResultsThe mean reduction of tumor motion amplitude was 3.5 mm (p = 0.009) for lower lobe tumors and 0.8 mm (p = 0.026) for upper/middle lobe locations. Compression increased tumor motion in 5 cases. Mean ITV reduction was 3.6 cm³ (p = 0.039) for lower lobe and 0.2 cm³ (p = 0.048) for upper/middle lobe lesions. Dosimetric gain of the compression for lung sparing was not clinically relevant.ConclusionsThe most significant impact of abdominal compression was obtained in patients with lower lobe tumors. However, minor or negative effects of compression were reported for other patients and lung sparing was not substantially improved. At our institute, patients with upper or middle lobe lesions are now systematically treated without compression and the usefulness of compression for lower lobe tumors is evaluated on an individual basis.     

Tumor Volume as an Alternative Response Measurement for Imatinib Treated GIST Patients

Background

Assessment of tumor size changes is crucial in clinical trials and patient care. We compared imatinib-induced volume changes of liver metastases (LM) from gastro-intestinal stromal tumors (GIST) to RECIST and Choi criteria and their association with overall survival (OS).

Methods

LM from 84 GIST patients (training and validation set) were evaluated using manual and semi-automated Computed Tomography measurements at baseline, after 3, 6 and 12 months of imatinib. The ability of uni-dimensional (1D) and three-dimensional (3D) measurements to detect size changes (increase/decrease) ≥20% was evaluated. Volumetric response cut-offs were derived from minimally relevant changes (+20/−30%) by RECIST, considering lesions as spherical or ellipsoidal.

Results

3D measurements detected size changes ≥20% more frequently than 1D at every time-point (P≤0.008). 3D and Choi criteria registered more responses than RECIST at 3 and 6 months for 3D-spheres (P≤0.03) and at all time-points for 3D-ellipsoids and Choi criteria (P<0.001). Progressive disease by 3D criteria seems to better correlate to OS at late time-points than other criteria.

Conclusion

Volume criteria (especially ellipsoids) classify a higher number of patients as imatinib-responders than RECIST. Volume discriminates size changes better than diameter in GIST and constitutes a feasible and robust method to evaluate response and predict patient benefit.     

Augmenting Entomopathogenic Nematodes in Soil from a Florida CitrusOrchard: Non-Target Effects of a Trophic Cascade

Laboratory experiments were conducted to study non-target effects of augmenting entomopathogenic nematode (EPN)communities in soil. When raw soil from a citrus orchard was augmented with either 2,000 Steinernema riobrave or S. diaprepesi, fewer EPN (P ≤ 0.05) survived if the soil had also been treated with 2,000 S. riobrave 7 d earlier (i.e., two augmentation events rather than one). EPN survival was unaffected by treatment (P ≤ 0.05) in soil that was air-dried to disrupt antagonist activity prior to the experiment. When S. diaprepesi, S. riobrave, Heterorhabditis zealandica or no EPN were added to raw soil and S. diaprepesi was added 5 d later, the survival of both S. diaprepesi and of total EPN was greater (P ≤ 0.05) in soil that received no pretreatment than in soilpre treated with S. riobrave. Pretreatment of soil with H. zealandica or S. diaprepesi had less or no affect on survival of S. diaprepesi or total EPN. When nematodes were recovered from soil and placed on water agar, the number of S. diaprepesi that were killed by endoparasitic and trapping nematophagous fungi was greater (P ≤ 0.05) if soil was pretreated with steinernematid species than if the soil was not pretreated or was pretreated with H. zealandica. The adverse effects of pretreating soil on EPN survival were density dependent within a range of pretreatment dosages (20–100 IJ/cm² soil surface), and the treatment effects required more time to become evident at lower than at higher dosages. These experiments suggest that non-target effects of augmenting the EPN community in soil vary among EPN species and have the potential to temporarily reduce EPN numbers below the natural equilibrium density.     

Lipiodol as an Imaging Biomarker of Tumor Response After Conventional Transarterial Chemoembolization: Prospective Clinical Validation in Patients with Primary and Secondary Liver Cancer

PURPOSE:To prospectively investigate whether Lipiodol can be used as a potential imaging biomarker of tumor response after conventional transarterial chemoembolization (cTACE) for both primary and secondary liver cancer. MATERIALS AND METHODS: This prospective single-center single-arm clinical trial enrolled a total of 39 patients with primary or secondary liver malignancy [hepatocellular carcinoma (HCC), n = 22 and non-HCC, n = 17]. Patients were treated with cTACE according to a standardized protocol and underwent multimodality imaging at baseline [magnetic resonance imaging (MRI)/computed tomography (CT)/positron emission tomography (PET)]; at 24 hours post-TACE (CT); and at 30, 90, and 180 days post-TACE (MRI/CT/PET). Image data analysis included quantitative assessment of tumor characteristics, Lipiodol deposition, fluorodeoxyglucose uptake, and tumor response assessment. Statistical analysis included linear regression, Student's t tests, Wilcoxon rank sum and signed rank test, Chi-square, and Fisher's exact test. RESULTS: Image analysis demonstrated that baseline tumor diameter (R² = 0.4, P = .0001), area (R² = 0.45, P < .0001), volume (R² = 0.3, P < .002), and enhancing volume (cm³, R² = 0.23, P < .002) at baseline correlated inversely with Lipiodol tumor coverage and response rates. Baseline tumor enhancement in % of the total tumor was the only parameter to positively correlate with Lipiodol coverage (R² = 0.189, P = .0456). Patients with high Lipiodol coverage of the tumors showed a higher tumor quantitative European Association for the Study of the Liver response rate at 30-day follow-up (P = .004). Lipiodol retention in both primary and secondary liver tumors was sustained over time, while nontarget hepatic deposits demonstrated near-complete elimination at 30-day follow-up (P < .001). CONCLUSION: Lipiodol deposition in liver tumors can be predicted using quantitative baseline imaging characteristics and correlates with tumor response. This supports another role for Lipiodol, namely, that of an imaging biomarker of tumor response after cTACE.     

仑伐替尼联合TACE对不可切除肝细胞癌患者肿瘤标志物、凋亡分子和血清ST6GAL1、ANG-2、HGF的影响

摘要 目的：探讨仑伐替尼联合肝动脉化疗栓塞术（TACE）对不可切除肝细胞癌患者肿瘤标志物、凋亡分子和血清唾液酸转移酶1（ST6Gal1）、血管生成素-2（ANG-2）、肝细胞生长因子（HGF）的影响。方法：采用随机数字表法将四川绵阳四0四医院2020年3月~2022年12月期间收治的114例不可切除肝细胞癌患者分为对照组（n=57,TACE治疗）和研究组（n=57,仑伐替尼联合TACE治疗）。对比两组疗效、肿瘤标志物[甲胎蛋白（AFP）、糖类抗原199（CA199）、癌胚抗原（CEA）]、血清凋亡分子[B淋巴细胞瘤-2相关X蛋白（Bax）、B淋巴细胞瘤-2基因（Bcl-2）、存活素（Survivin）、半胱氨酸天冬氨酸蛋白酶-4（Caspase-4）]和血清ST6Gal1、ANG-2、HGF水平,并观察两组治疗期间不良反应发生情况。结果：与对照组相比,研究组的临床总有效率更高（P<0.05）。与对照组相比,研究组治疗后AFP、CA199、CEA水平更低（P<0.05）。与对照组相比,研究组治疗后Bcl-2、Survivin水平更低,Bax、Caspase-4水平更高（P<0.05）。与对照组相比,研究组治疗后ST6Gal1、ANG-2、HGF水平更低（P<0.05）。两组不良反应总发生率组间对比未见差异（P>0.05）。结论：仑伐替尼联合TACE用于不可切除肝细胞癌患者,可提高临床治疗效果,调节肿瘤标志物、凋亡分子和血清ST6Gal1、ANG-2、HGF水平,安全性较好。