Sorafenib Plus Hepatic Arterial Infusion Chemotherapy versus Sorafenib for Hepatocellular Carcinoma with Major Portal Vein Tumor Thrombosis: A Randomized Trial.

Background The prognosis of hepatocellular carcinoma (HCC) with major portal vein tumor thrombosis (PVTT) is dismal after standard treatment with sorafenib. Hepatic arterial infusion chemotherapy (HAIC) has been suggested for patients with HCC and major PVTT. Purpose To compare the efficacy and safety of sorafenib plus 3cir-OFF HAIC versus sorafenib alone for advanced HCC with major PVTT. Materials and Methods This phase II trial recruited systemic treatment-naïve patients with HCC and major PVTT (portal vein invasion grade Vp3 [first branch] and Vp4 [main trunk]) between June 2017 and November 2019. Patients were randomly assigned (1:1 ratio) to receive sorafenib (400 mg twice daily) plus 3cir-OFF HAIC (35 mg/m2 oxaliplatin [hours 0-2] followed by 600 mg/m2 5-fluorouracil [hours 2-24], days 1-3) with a standardized percutaneous port catheter system or sorafenib alone (400 mg twice daily) every 4 weeks. The primary end point was overall survival (OS). The secondary end points were objective response rate, progression-free survival (PFS), and safety. OS and PFS were assessed using the Kaplan-Meier method and log-rank test. Results The intent-to-treat population included 64 patients, with 32 in each group. The median OS was 16.3 months (95% CI: 0.0, 35.5) with sorafenib plus HAIC and 6.5 months (95% CI: 4.4, 8.6) with sorafenib alone (hazard ratio [HR] = 0.28; 95% CI: 0.15, 0.53; P < .001). A higher objective response rate (41% [n = 13] vs 3% [n = 1], P < .001) and a longer median PFS (9.0 months vs 2.5 months; HR = 0.26; 95% CI: 0.15, 0.47; P < .001) were observed in the sorafenib plus HAIC group. Grade 3 or 4 adverse events were more frequent in the sorafenib plus HAIC group, including diarrhea (n = 7 [22%] vs n = 5 [16%]), hand-foot syndrome (n = 6 [19%] vs n = 2 [6%]), and thrombocytopenia (n = 7 [22%] vs n = 0). Conclusion Sorafenib plus 3cir-OFF hepatic arterial infusion chemotherapy may be a promising treatment in patients with hepatocellular carcinoma and major portal vein tumor thrombosis because of the improved survival and an acceptable safety profile. Clinical trial registration no. NCT03009461 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Chung in this issue.

MRI in predicting the response of gastrointestinal stromal tumor to targeted therapy: a patient-based multi-parameter study.

BACKGROUND: To investigate the performance of quantitative indicators of MRI in early prediction of the response of gastrointestinal stromal tumor (GIST) to targeted therapy in a patient-based study. METHODS: MRI examinations were performed on 62 patients with GIST using 1.5 T scanners before and at two and 12 weeks after treatment with targeted agents. The longest diameter (LD) and contrast-to-noise ratio (CNR) of the tumors were measured by T2-weighted imaging (T2WI), and the apparent diffusion coefficient (ADC) was determined using diffusion-weighted imaging (DWI). The pre-therapy and early percentage changes (%Δ) of the three parameters were compared with regard to their abilities to differentiate responder and non- responder patients, using ROC curves. RESULTS: There were 42 patients in responder and 20 in non-responder group. After two weeks of therapy, the percentage changes in the ADC and LD were significantly different between the two groups (ADC: responder 30% vs. non- responder 1%, Z = - 4.819, P < 0.001; LD: responder - 7% vs. non- responder - 2%, Z = - 3.238, P = 0.001), but not in T2WI-CNR (responder - 3% vs. non-responder 9%, Z = - 0.663, P = 0.508). The AUCs on ROC for %ΔLD, %ΔT2WI-CNR and %ΔADC after two weeks of therapy were 0.756, 0.552 and 0.881, respectively, for response differentiation. When %ΔADC ≥15% was used to predict responder, the PPV was 93.3%. CONCLUSIONS: The percentage change of the ADC after two weeks of therapy outperformed T2WI-CNR and longest diameter in predicting the early response of GIST to targeted therapy.

Phase II study of weekly irinotecan and capecitabine treatment in metastatic colorectal cancer patients.

BACKGROUND: The purpose of this phase II study was to evaluate the safety and efficacy of weekly irinotecan and capecitabine (wXELIRI) treatment in patients with metastatic colorectal cancer, specifically the rate of severe diarrhea. METHODS: Patients with unresectable histologically confirmed metastatic colorectal cancer with measurable disease received weekly irinotecan 90 mg/m² on day 1 and capecitabine 1200 mg/m² twice daily on days 1-5. Patients naïve to systemic chemotherapy for metastatic disease or who had failed FOLFOX (infusional 5-fluorouracil [5-FU], leucovorin, and oxaliplatin) or XELOX (capecitabine plus oxaliplatin) as first-line treatment were eligible. The primary endpoint was the rate of grade 3/4 diarrhea. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. RESULTS: A total of 52 patients were enrolled, 30 of whom received wXELIRI as first-line treatment and 22 as second-line treatment. Grade 4 diarrhea was observed in one patient and the rate of grade 3/4 diarrhea was 7.7%. The other common grade 3/4 toxicities included leukopenia (9.6%), neutropenia (17.3%), nausea (3.8%), vomiting (3.8%), fatigue (1.9%), and hand-foot syndrome (1.9%). The median progression-free survival and overall survival for the 30 patients treated in the first-line setting was 8.5 and 16.3 months, while those for the 22 patients treated in the second-line setting was 5.0 and 10.7 months, respectively. CONCLUSIONS: The wXELIRI regimen resulted in a low rate of severe diarrhea with an acceptable toxicity profile. This study provides a basis for a subsequent randomized controlled study of wXELIRI versus FOLFIRI (irinotecan, 5-FU, and folinic acid) to further explore the efficacy and safety of this regimen. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01322152.

The efficacy of autologous matrix-induced chondrogenesis (AMIC) for osteochondral lesions of the talus in the mid-long term: a systematic review and meta-analysis.

PURPOSE: The objective of this study was to provide a comprehensive review of the existing literature regarding the treatment of osteochondral lesions of the talus (OLT) using autologous matrix-induced chondrogenesis (AMIC), while also discussing the mid-long term functional outcomes, complications, and surgical failure rate. METHODS: We searched Embase, PubMed, and Web of Science for studies on OLT treated with AMIC with an average follow-up of at least 2 years. Publication information, patient data, functional scores, surgical failure rate, and complications were extracted. RESULTS: A total of 15 studies were screened and included, with 12 case series selected for meta-analysis and 3 non-randomized controlled studies chosen for descriptive analysis. The improvements in the Visual Analog Scale (VAS), the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot, and Tegner scores at the last follow-up were (SMD = - 2.825, 95% CI - 3.343 to - 2.306, P < 0.001), (SMD = 2.73, 95% CI 1.60 to 3.86, P < 0.001), (SMD = 0.85, 95% CI 0.5 to 1.2, P < 0.001) respectively compared to preoperative values. The surgery failure rate was 11% (95% CI 8-15%), with a total of 12 patients experiencing complications. CONCLUSION: The use of AMIC demonstrates a positive impact on pain management, functional improvement, and mobility enhancement in patients with OLT. It is worth noting that the choice of stent for AMIC, patient age, and OLT size can influence the ultimate clinical outcomes. This study provides evidences supporting the safety and efficacy of AMIC as a viable treatment option in real-world medical practice.

The landscape of cancer research and cancer care in China.

The rising cancer incidence rate in China poses a substantial public health concern, although there have been remarkable improvements in the country's cancer mortality and survival rates. In this Review, we outline the current landscape and future directions of cancer care and research in China. We discuss national screening programs and strategies for cancer detection and delve into the evolving landscape of cancer care, emphasizing the adoption of multidisciplinary, comprehensive treatment and precision oncology. Additionally, we examine changes in drug research and development policies that have enabled approval of new drugs. Finally, we look to the future, highlighting key priorities and identifying gaps. Effectively addressing challenges and seizing opportunities associated with cancer research in China will enable the development of targeted approaches to alleviate the global burden of cancer.

Randomized phase II study of capecitabine plus cisplatin with or without sorafenib in patients with metastatic gastric cancer (STARGATE).

BACKGROUND: In this randomized phase II study, we evaluated the efficacy and safety of sorafenib in combination with capecitabine and cisplatin (XP) as first-line chemotherapy in advanced gastric cancer. PATIENTS AND METHODS: Patients with metastatic gastric or gastroesophageal junction adenocarcinoma were randomized (1:1) to receive either sorafenib plus XP (S + XP) or XP alone. In cases of disease progression in the XP arm, crossover to sorafenib alone was allowed. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), response rates, safety profiles, and biomarkers, and the response rates and PFS with secondline sorafenib alone after progression in the XP arm. RESULTS: Between Jan 2011 and Feb 2013, a total of 195 patients were accrued (97 in the S + XP arm and 98 in the XP alone arm). The overall response rate was 54% with S + XP, and 52% with XP alone (p = 0.83). With a median follow-up of 12.6 months (range, 0.1-29.2), the median PFS assessed by independent review was 5.6 months in the S + XP arm and 5.3 months in the XP arm (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.67-1.27, p = 0.61). Overall survival was not different between the two arms (median 11.7 vs. 10.8 months; HR 0.93, 95% CI 0.65-1.31, p = 0.66). Frequencies of grade 3/4 toxicities were similar between the S + XP and XP alone arms, except for neutropenia (21% vs. 37%), anorexia (0% vs. 5%), and hand-foot skin reaction (7% vs. 1%). Among 51 patients who crossed over to sorafenib alone after disease progression in the XP arm, there was no objective response and their median PFS was 1.3 months (95% CI, 1.2-1.7). CONCLUSION: The addition of sorafenib to XP chemotherapy was safe but not more effective than XP alone for first-line treatment of metastatic gastric cancer.

Cancer tracking system improves timeliness of liver cancer care at a Veterans Hospital: A comparison of cohorts before and after implementation of an automated care coordination tool.

INTRODUCTION: Hepatocellular carcinoma (HCC) requires complex care coordination. Patient safety may be compromised with untimely follow-up of abnormal liver imaging. This study evaluated whether an electronic case-finding and tracking system improved timeliness of HCC care. METHODS: An electronic medical record-linked abnormal imaging identification and tracking system was implemented at a Veterans Affairs Hospital. This system reviews all liver radiology reports, generates a queue of abnormal cases for review, and maintains a queue of cancer care events with due dates and automated reminders. This is a pre-/post-intervention cohort study to evaluate whether implementation of this tracking system reduced time between HCC diagnosis and treatment and time between first liver image suspicious for HCC, specialty care, diagnosis, and treatment at a Veterans Hospital. Patients diagnosed with HCC in the 37 months before tracking system implementation were compared to patients diagnosed with HCC in the 71 months after its implementation. Linear regression was used to calculate mean change in relevant intervals of care adjusted for age, race, ethnicity, BCLC stage, and indication for first suspicious image. RESULTS: There were 60 patients pre-intervention and 127 post-intervention. In the post-intervention group, adjusted mean time from diagnosis to treatment was 36 days shorter (p = 0.007), time from imaging to diagnosis 51 days shorter (p = 0.21), and time from imaging to treatment 87 days shorter (p = 0.05). Patients whose imaging was performed for HCC screening had the greatest improvement in time from diagnosis to treatment (63 days, p = 0.02) and from first suspicious image to treatment (179 days, p = 0.03). The post-intervention group also had a greater proportion of HCC diagnosed at earlier BCLC stages (p<0.03). CONCLUSIONS: The tracking system improved timeliness of HCC diagnosis and treatment and may be useful for improving HCC care delivery, including in health systems already implementing HCC screening.

[Bloodletting acupuncture at jing-well points along three-yang meridians of foot combined with acupuncture on migraine:a randomized controlled trial].

OBJECTIVE: To compare the analgesic effect of bloodletting acupuncture at jing-well points along three-yang meridians of foot combined with routine acupuncture and simple routine acupuncture on migraine. METHODS: A total of 60 patients with migraine were randomized into an observation group and a control group, 30 cases in each one, of which, 4 cases were dropped out in the observation group, 1 case was dropped out in the control group. In the observation group, bloodletting acupuncture at jing-well points combined with routine acupuncture were applied. The bloodletting acupuncture was applied at corresponding jing-well points of three-yang meridians of foot [Lidui (ST 45), Zhiyin (BL 67), Zuqiaoyin (GB 44)] according to pain location. And routine acupuncture was adopted at Sizhukong (TE 23), Shuaigu (GB 8), Taiyang (EX-HN 5), Fengchi (GB 20), Hegu (LI 4), Taichong (LR 3), Zulinqi (GB 41), Yanglingquan (GB 34) and Waiguan (TE 5). In the control group, routine acupuncture was applied, acupoint selection and operation were the same as the observation group. The treatment was given once a day, 30 min a time, 5 days as one course with 2 days interval, and 2 courses were required. Before treatment, immediately after needle withdrawal, 4 h after needle withdrawal and after 2 courses of treatment, the visual analogue scale (VAS) score was compared in the two groups. Before and after treatment, the migraine comprehensive score was observed in the two groups, and the therapeutic effect was evaluated. RESULTS: Immediately after needle withdrawal, 4 h after needle withdrawal and after 2 courses of treatment, the VAS scores in the two groups were decreased (P<0.05), the VAS scores immediately after needle withdrawal, 4 h after needle withdrawal and after 2 courses of treatment in the observation group were lower than those in the same time of the control group (P<0.05). After treatment, the migraine comprehensive scores in the two groups were decreased (P<0.05), the reducing degree in the observation group was greater than the control group (P<0.05). The total effective rate in the observation group was 92.3% (24/26), which was higher than 89.7% (26/29) in the control group, there was no significant difference (P>0.05). CONCLUSION: Bloodletting acupuncture at jing-well points along three-yang meridians of foot combined with routine acupuncture and simple routine acupuncture have analgesic effect, and the combined therapy is superior to simple routine acupuncture.

Effects of intensity of electroacupuncture on chronic pain in patients with knee osteoarthritis: a randomized controlled trial.

BACKGROUND: Conditioned pain modulation (CPM) is impaired in people with chronic pain such as knee osteoarthritis (KOA). The purpose of this randomized, controlled clinical trial was to investigate whether strong electroacupuncture (EA) was more effective on chronic pain by strengthening the CPM function than weak EA or sham EA in patients with KOA. METHODS: In this multicenter, three-arm parallel, single-blind randomized controlled trial, 301 patients with KOA were randomly assigned. Patients were randomized into three groups based on EA current intensity: strong EA (> 2 mA), weak EA (< 0.5 mA), and sham EA (non-acupoint). Treatments consisted of five sessions per week, for 2 weeks. Primary outcome measures were visual analog scale (VAS), CPM function, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: Three hundred one patients with KOA were randomly assigned, among which 271 (90.0%) completed the study (mean age 63.93 years old). One week of EA had a clinically important improvement in VAS and WOMAC but not in CPM function. After 2 weeks treatment, EA improved VAS, CPM, and WOMAC compared with baseline. Compared with sham EA, weak EA (3.8; 95% CI 3.45, 4.15; P < .01) and strong EA (13.54; 95% CI 13.23, 13.85; P < .01) were better in improving CPM function. Compared with weak EA, strong EA was better in enhancing CPM function (9.73; 95% CI 9.44, 10.02; P < .01), as well as in reducing VAS and total WOMAC score. CONCLUSION: EA should be administered for at least 2 weeks to exert a clinically important effect on improving CPM function of KOA patients. Strong EA is better than weak or sham EA in alleviating pain intensity and inhibiting chronic pain. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry ( ChiCTR-ICR-14005411 ), registered on 31 October 2014.

[Effects of Migu Tablet on bone mineral density, serum levels of osteoprotegerin and its ligand and bone metabolic markers in patients with postmenopausal osteoporosis].

OBJECTIVE: To study the effects of Migu Tablet (MGT) on bone mineral density (BMD), serum levels of osteoprotegerin (OPG) and its ligand (OPGL), and bone metabolic markers in patients with postmenopausal osteoporosis (PMO). METHODS: BMD in 192 women of natural menopause, 48 to 65 years old, were determined. Among them, 160 women with PMO were randomized into 4 groups, 54 in the Migu Tablet group (MGTG), 53 in the Xianlin Gubao group (XLGBG) and 53 in the Leli Calcium group (LCG). And the other 32 women with BMD in normal range were set as the control group. Serum levels of OPG, OPGL, bone alkaline phosphates (sBAP), osteocalcin (sOC), cross-linked C-telopeptides of collagen type I (sCTx), and urine level of bone cross-linked N-telopeptides of collagen type I (uNTx) were measured before treatment and at the 12th and 24th week of treatment, with enzyme-linked immunosorbent assay (ELISA); BMD of orthophoric lumbar vertebrae, femoral neck, Ward's triangle and trochanter were determined by dual-energy X-ray absorptiometry at the same time as well. RESULTS: After 24-week treatment, BMD was heightened to different degree, serum levels of OPG, sCTx, uNTx/Cr were significantly decreased and OPGL, sBAP, sOC were increased in the MGTG and XLGBG, while these indexes showed insignificant change in the LCG and the control group. CONCLUSION: The effect of MGT in treating PMO were notable, just like that of XLGB, but single medication of calcium tablet cannot alleviate the disease and also incapable to prevent the loss of bone.

Evaluation of multi-dimensional outcomes of chronic diseases: a clinical example from China.

The purpose of this study is to provide the evidence of individualized/personalized care by evaluating multi-dimensional outcomes of chronic diseases in the elderly. We used primary osteoporosis as an example, to evaluate the outcomes of three treatments (calcium combined vitamin D=Ca+vit.D; estrogen and disphosphonates) at the same time with biological dimension (bone-mineral density=BMD) and socio-psychological dimension (health-related quality of life=HR-QOL), using the medical outcomes study short-form 36-item health survey (SF-36) and cost dimension (drug cost). Using BMD as the outcome index, disphosphonate was the most effective treatment, in terms of HR-QOL, estrogen was the most effective while Ca+vit.D was the cheapest treatment, namely, different dimensional outcomes with different results. Outcome evaluation of chronic diseases in the elderly needs to combine psychological and socio-economic parameters together with the physiological measurement, to encourage a transition from "the disease-centered" to "the patient-centered" perspective as well as achieve sustainable and coordinated development of health and socio-economic resources.

Two-dose-level confirmatory study of the pharmacokinetics and tolerability of everolimus in Chinese patients with advanced solid tumors.

BACKGROUND: This phase I, randomized, multicenter, open-label study investigated the pharmacokinetics, safety, and efficacy of the oral mammalian target of rapamycin inhibitor everolimus in Chinese patients with advanced solid tumors. METHODS: A total of 24 patients with advanced breast cancer (n = 6), gastric cancer (n = 6), non-small cell lung cancer (n = 6), or renal cell carcinoma (n = 6) who were refractory to/unsuitable for standard therapy were randomized 1:1 to oral everolimus 5 or 10 mg/day. Primary end points were pharmacokinetic parameters and safety and tolerability. Pharmacokinetic 24-h profiles were measured on day 15; trough level was measured on days 2, 8, 15, 16, and 22. Tolerability was assessed continuously. This final analysis was performed after all patients had received 6 months of study drug or had discontinued. RESULTS: Everolimus was absorbed rapidly; median Tmax was 3 h (range, 1-4) and 2 h (range, 0.9-6) in the 5 and 10 mg/day groups, respectively. Pharmacokinetic parameters increased dose proportionally from the 5 and 10 mg/day doses. Steady-state levels were achieved by day 8 or earlier. The most common adverse events suspected to be related to everolimus therapy were increased blood glucose (16.7% and 41.7%) and fatigue (16.7% and 33.3%) in the everolimus 5 and 10 mg/day dose cohorts, respectively. Best tumor response was stable disease in 10 (83%) and 6 (50%) patients in the 5 and 10 mg/day groups, respectively. CONCLUSIONS: Everolimus 5 or 10 mg/day was well tolerated in Chinese patients with advanced solid tumors. The observed safety and pharmacokinetic profile of everolimus from this study were consistent with previous studies. TRIAL REGISTRATION: Chinese Health Authorities 2008L09346.

Açäo, "in vitro", da violeta de genciana sobre formas evolutivas do Plasmodium falciparum / In vitro activity of gentian violet on asesenal Plasmodium falciparum

Utilizando a técnica de RIECKMANN e col., os autores realizaram 20 microtestes de sensibilidade, procurando verificar a capacidade da violeta de genciana em impedir, na cultura "in vitro", o desenvolvimento habitual do Plasmodium falciparum. Os resultados mostraram que houve inibiçäo da evoluçäo do protozoário nas concentraçöes de 1/1000, 1/1500, 1/2000, 1/2500, 1/3000 e 1/4000, significando que nas condiçöes da experiência o corante atuou sobre as formas sanguíneas assexuadas do protozoário. Estas verificaçöes sugerem que a violeta de genciana poderia ser usada na profilaxia da malária transfusional