Transarterial Infusion Chemotherapy Research Articles

Bland Embolization and Transarterial Chemoembolization in Hepatocarcinoma

AbstractHepatocarcinoma (HCC) is the main cause of morbidity and mortality worldwide in patients with cirrhosis. Eighty percent of cases worldwide are due to infections with hepatitis B and C viruses, but nonalcoholic steatohepatitis (NASH) is projected to be an important etiology. It is usually diagnosed in advanced stages, only 15% of patients are surgical candidates, and up to 35% can receive only supportive care. This pathology has changed over time with the significant advances in treatment alternatives that can improve life expectancy for patients who are not surgical candidates. Therapeutic alternatives are available based on staging according to different models and the Barcelona Clinic Liver Cancer (BCLC) staging system. Systemic pharmacological options (neoadjuvant, adjuvant, and hormonal therapy), surgical options, and locoregional therapies have been developed; all these interventions have been directed to increase the life expectancy of some patients with variable results. Regional therapies include transarterial embolization (TAE) or bland embolization, transarterial infusion chemotherapy, conventional transarterial chemoembolization (TACE), drug-eluting bead transarterial chemoembolization (DEB-TACE), and transarterial radioembolization, with no substantial difference in outcomes between patients treated with TACE and those receiving DEB-TACE, but benefits of lower systemic adverse effects and improved of quality-adjusted life years measure with DEB-TACE. With the addition of immunotherapy to these interventions, the outcomes are expected to be even more impactful on main outcomes such as survival and disease-free survival.

Transarterial infusion chemotherapy for advanced esophageal cancer with airway stenosis.

This study aimed to investigate the safety and efficacy of transarterial infusion chemotherapy for the treatment of esophageal cancer with airway stenosis. Data of patients with advanced esophageal cancer complicated with airway stenosis treated with transarterial infusion chemotherapy were retrospectively analyzed. Dyspnea, clinical efficacy and adverse reactions were evaluated. Of these patients, 27 had grade II preoperative dyspnea, and 31 had grade III preoperative dyspnea, 26 had grade I postoperative dyspnea, 25 had grade II postoperative dyspnea, and 7 had grade III postoperative dyspnea. Among 3 patients with left main bronchial stenosis and atelectasis, 2 had complete remission after transarterial infusion chemotherapy, and 1 demonstrated partial remission. After treatment, complete response, partial response, and stable disease were observed in 7, 34, and 17 cases, respectively. Total objective effective rate and disease control rate were 70.6% (41/58) and 100.0%, respectively. During follow up, 24 patients died of organ failure, and 17 patients died of tumor-related respiratory failure. Seven patients died of gastrointestinal bleeding, 1 patient died of myocardial infarction, and 9 patients survived. Transarterial infusion chemotherapy is safe and effective for the treatment of advanced esophageal cancer with airway stenosis.

Hepatic artery infusion chemotherapy for advanced hepatocellular carcinoma

Objective:This study’s purpose was to evaluate the response, safety and overall survival of trans-arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma with preserved hepatic function.Methods:This study was carried out on 25 patients, diagnosed with hepatocellular carcinoma (HCC) combined with portal vein tumor thrombosis (PVTT) and underwent hepatic artery infusion chemotherapy (HAIC). Radiological investigations as Triphasic CT or dynamic MRI liver assessment pre and post therapy were acquired. Intra-Arterial chemotherapeutic agent infusion using only doxorubicin was performed.Results:Neither of the patients who underwent HAIC developed complete or partial response. Only one patient (4.8%) from 21 patients under HAIC had stable disease. 20 patients (95%) had progressive disease. Progressive disease was in form of progression at the primary tumor site in form of increased focal lesion size, number or vascular invasion. Vascular invasion was seen in one patient (4.8%) in the form of hepatic vein thrombosis. Mean progression free survival was about 2.24 ± 0.88 months. Mean overall survival was about 5.72 ± 0.89 months.Conclusion:Our study demonstrated lower clinical efficacy and lower disease control rate of repeated HAIC using doxorubicin only infusion in case of advanced HCC with PVT as compared to combined doxorubicin and cisplatin in previous studies as well as the standard therapy with sorafenib.

Lenvatinib combined with hepatic arterial infusion of modified FOLFOX regime as an initial treatment in patients with intermediate-stage hepatocellular carcinoma beyond up-to-seven criteria.

e16154 Background: Transcatheter arterial chemoembolization (TACE) is not effective for intermediate-stage hepatocellular carcinoma (HCC) beyond up-to-seven criteria (substage B2) and also impairs the hepatic functional reserve, resulting in poor prognosis. This study aimed to investigate the efficacy and safety of lenvatinib combined transarterial infusion chemotherapy with FOLFOX regimen (FOLFOX-HAIC) for substage B2 HCC. Methods: This study retrospectively enrolled and analyzed 18 patients with substage B2 HCC from Nov. 2019 to Nov. 2021. Patients were orally administered with 8 mg(≤60kg) or 12mg(> 60kg) lenvatinib once daily initially, and FOLFOX-HAIC (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2,400 mg/m2 for 46 hours) was performed every 3 weeks and up to 6 sessions. Then patients were treated with lenvatinib alone. Patients with downsizing HCC was allowed for potential curative therapies (surgical resection or ablation). Best response according to the RECIST 1.1 and mRECIST criteria, progression-free survival (PFS) and treatment-related adverse events (TRAE) were evaluated. Results: 18 patients (median age: 63.0 years) underwent a total of 77 cycles of HAIC therapy (mean: 4.3; range: 2-6). All patients were classified as Child-Pugh A class. The ORR were 83.3% (RECIST 1.1) and 94.4% (mRECIST), the disease control rate (DCR) was 100% (RECIST1.1/mRECIST). With a median follow-up period of 12.9 months, the median PFS was 10 months. During the follow-up period, no patient died, and 8 of 18 (44.4%) patients experienced progression. 6-, 9-, and 12-months PFS rates were 94%, 74%, and 55%, respectively. TRAE occurred in 15 of 18 patients (83.3%). Two grade 3 TRAE (hepatic encephalopathy and hypertension) was observed. Conclusions: Lenvatinib combined with FOLFOX-HAIC was well tolerated and had shown promising ORR, PFS rates in patients with intermediate-stage HCC beyond up-to-seven criteria. A prospective large-scale trial is needed to justify these results. [Table: see text]

Sequential treatment of severe airway stenosis caused by esophageal cancer by using airway stent implantation and arterial infusion chemotherapy

The purpose of this clinical study was to investigate the efficacy and safety of airway stent implantation and transarterial infusion chemotherapy in the sequential treatment of severe airway stenosis caused by esophageal cancer. Data of patients with advanced esophageal cancer complicated by severe airway stenosis treated with airway stent implantation and transarterial infusion chemotherapy were retrospectively analyzed. Furthermore, dyspnea, clinical efficacy, adverse reactions, and survival of patients were evaluated. 71 patients were included in this study. There were 28 patients with grade III dyspnea and 43 patients with grade IV dyspnea before airway stent implantation, and 34 patients with grade I dyspnea, 35 patients with grade II dyspnea and 2 patients with grade III dyspnea after airway stent implantation. After airway stent implantation and 1–3 courses of transarterial infusion chemotherapy, 11, 41 and 19 patients had complete response, partial response and stable response respectively. Total disease control rate (DCR) and objective response rate (ORR) were 100.0% and 73.2%, respectively. During the follow-up, 32 patients died of organ failure, 24 patients died of tumor-related respiratory failure, and 10 patients died of gastrointestinal bleeding. The median survival time of all patients was 8 months, and the 1-year survival rate was 40.8%. Airway stent implantation combined with arterial infusion chemotherapy is safe and effective for sequential treatment of esophageal cancer with severe airway stenosis.

Transarterial Infusion Chemotherapy with FOLFOX Could be an Effective and Safe Treatment for Unresectable Intrahepatic Cholangiocarcinoma.

Background Transarterial infusion (TAI) chemotherapy with the FOLFOX regimen has shown good efficacy and safety in the treatment of hepatocellular carcinoma (HCC). However, it has not been reported in intrahepatic cholangiocarcinoma (ICC). Methods The data of consecutive patients with unresectable ICC who underwent TAI with the FOLFOX regimen from November 2016 to September 2019 were retrospectively analyzed. Treatment effectiveness and safety were evaluated and compared using the Kaplan–Meier method, log-rank test, Cox regression models, and χ2 test. Results Twenty-nine patients were included in the study. The median overall survival (OS) was 16.2 months (95% CI, 13.0–19.4). The median progression-free survival (PFS) was 8.7 months (95% CI, 6.2–11.1). Twenty-seven patients were included in the efficacy analysis. There were 0, 10, 13, and 4 patients with CR, PR, SD, and PD, respectively, based on mRECIST criteria. The ORR was 37.0%, and the DCR was 85.2%. There were 27 patients (93.1%) who experienced grade 1-2 AEs, while only 1 patient experienced grade 3 AEs. Conclusion TAI with the FOLFOX regimen could be an effective and safe treatment for unresectable ICC.

Transarterial infusion chemotherapy with FOLFOX for advanced hepatocellular carcinoma: a multi-center propensity score matched analysis of real-world practice.

To compare the treatment effectiveness and safety among transarterial infusion chemotherapy (TAI) with FOLFOX regimen, transarterial chemoembolization (TACE), and sorafenib in patients with BCLC stage C hepatocellular carcinoma (HCC). The data of consecutive patients with BCLC stage C HCC treated with TAI, TACE, or sorafenib from January 2015 to December 2018 at three centers were retrospectively analyzed. Propensity-score matched (PSM) analysis was pairwise performed to reduce selection bias. Treatment effectiveness and safety were evaluated and compared using the Kaplan-Meier method, log-rank test, Cox regression models, and χ2 test. The median overall survival (OS) in the matched TAI cohort was significantly longer than the sorafenib cohort (19.6 vs. 7.5 months, P=0.009), and the TACE cohort (estimated 27.8 vs. 6.6 months, P<0.001). The difference in median progression-free survival (PFS) between the matched TAI and sorafenib cohorts was not significant (5.8 vs. 2.3 months, P=0.219). The median PFS in the matched TAI cohort was significantly longer than the TACE cohort (6.5 vs. 2.8 months, P<0.001). The objective response rate (ORR) in the matched TAI cohort was significantly higher than the sorafenib cohort (36.4% vs. 0.0%, P<0.001) and the TACE cohort (48.7% vs. 4.7%, P<0.001). The incidences of adverse events (AEs) were similar among these three cohorts. TAI with FOLFOX regimen was an effective and safe therapy that improved survival of patients with BCLC stage C HCC.

Neoadjuvant transarterial infusion chemotherapy with FOLFOX could improve outcomes of resectable BCLC stage A/B hepatocellular carcinoma patients beyond Milan criteria: An interim analysis of a multi-center, phase 3, randomized, controlled clinical trial.

4008 Background: The efficacy of operation, as the only radical option for resectable BCLC stage A/B hepatocellular carcinoma (HCC) patients beyond Milan criteria, is still unsatisfactory. This study aimed to investigate to efficacy and safety of preoperative neoadjuvant transarterial infusion chemotherapy (TAI) with FOLFOX regimen for these patients. Methods: In this multi-center, prospective, phase 3, randomized, open-labeled, controlled clinical trial, resectable BCLC stage A/B HCC patients beyond Milan criteria were randomly assigned (1:1) before hepatectomy to receive either neoadjuvant TAI (NT group) or operation directly without any neoadjuvant treatment (OP group). The primary endpoint was overall survival (OS), the secondary endpoints are progression-free survival (PFS), recurrence free survival (RFS), and safety. Results: Between March, 2016 and July, 2020, 208 patients enrolled from five Chinese hospitals were randomly assigned to NT group (n=104) or OP group (n=104)， with 99 patients in NT group and 100 patients in OP group included in the efficacy and safety analysis. Clinicopathological characteristics were balanced between the two groups. The 1-, 2-, and 3-year OS rates for NT group were 92.9%, 78.6%, and 63.5%, and were 79.5%, 62.0%, and 46.3% for OP group, respectively. The 6-, 12-, and 18-month PFS rates for NT group were 77.6%, 50.4%, and 47.4%, and were 52.7%, 42.8%, and 34.8% for OP group, respectively. The OS and PFS were significantly better in NT group than in OP group (p=0.016 and 0.017, respectively). The 6-, 12-, and 18-month RFS rates for NT group were 63.8%, 47.3%, and 47.3%, and were 52.7%, 42.8%, and 34.8% for OP group, respectively. The RFS between the two group had no difference (p=0.385). No patients in NT group experienced grade 3 or more severe TAI related adverse events. The operation related adverse events were similar between two groups (p=0.300). Conclusions: Neoadjuvant TAI before hepatectomy may bring survival benefits for resectable BCLC stage A/B HCC patients beyond Milan criteria. Trial number: NCT03851913. Clinical trial information: NCT03851913.

Gastroesophageal junction cancer with hepatic metastasis: Effective Treatment using microsphere embolization combined with transarterial infusion chemotherapy

PurposeTo determine the safety and efficacy of microsphere embolization plus transarterial infusion chemotherapy for the treatment of gastroesophageal junction cancer with hepatic metastasis. MethodsSixty patients with gastroesophageal junction cancer and hepatic metastasis were randomly divided into two groups: group A (treatment group), which was treated with transarterial infusion chemotherapy plus microsphere embolization for gastroesophageal cancer, and with transarterial chemoembolization for hepatic metastasis; and group B (control group), which was treated with transarterial infusion chemotherapy for gastroesophageal cancer, and with transarterial chemoembolization for hepatic metastasis. The chemotherapy regimen used consisted of oxaliplatin plus FUDR. The embolization agent used for gastroesophageal cancer and the hepatic metastasis were Embosphere and ultra-liquefied lipiodol, respectively. ResultsThe median survival time of patients in group A was 19 months, with survival rates at 12, 18, and 24 months of 93.3%, 60.0%, and 23.3%, respectively. The median survival time of patients in group B was 13 months, with survival rates at 12, 18, and 24 months of 60.0%, 30.0%, and 3.3%, respectively. There was a significant difference in survival between the two groups (P = 0.00). One month after treatment, the severity of dysphagia was significantly less in group A, as compared to that in group B (p < 0.001). ConclusionTreatment of gastroesophageal junction cancer with hepatic metastasis by transarterial infusion chemotherapy plus microsphere embolization can rapidly reduce tumor size near the gastroesophageal junction. This treatment is an effective therapeutic option for these patients as it can relieve dysphagia and improve long-term survival rate.

Clinical Evaluation of Transarterial Infusion Chemotherapy for Advanced Esophageal Cancer.

Background: Most esophageal cancer patients are diagnosed at an advanced stage when there are few effective treatments. Transarterial infusion chemotherapy is a local chemotherapy method wherein chemotherapeutic drugs are directly injected into tumor vessels.Methods: Transarterial infusion chemotherapy was performed on advanced esophageal cancer patients once a month, and each patient underwent 1-3 treatments. The clinical results, complications, and effectiveness rates of each treatment episode were recorded and analyzed.Results: Transarterial infusion chemotherapy was successfully performed in all patients, and no severe complications such as paraplegia or death were noted. Complete response, partial response, and stable disease were noted in 17.3% (13/75), 77.3% (58/75), and 5.3% (4/75) of cases after transarterial infusion chemotherapy, respectively. The total treatment efficacy (complete response + partial response) was 94.7%. All cases exhibited improvement in clinical stage, with a marked decrease in dysphagia. Subsequent treatments were administered to 13 patients, including radical radiation in 7 and chemotherapy in 6. During follow-up, death was caused by progressive carcinoma in 20, tumor-related pneumatic infection and respiratory failure in 11, and gastrointestinal hemorrhage in 17. The median survival time was 15 months and the 1-year survival rate was 58.1%.Conclusions: Transarterial infusion chemotherapy may be safely and effectively used for treatment of advanced esophageal cancer.

A novel combination of percutaneous stenting with iodine-125 seed implantation and chemotherapy for the treatment of pancreatic head cancer with obstructive jaundice

PurposeInsertion of radioactive strips through the biliary stent has been reported to offer longer survival and patency than an uncovered conventional self-expanding metal stent in patients with unresectable malignant biliary obstruction. The aim of this study was to investigate the safety and effectiveness of intraluminal brachytherapy combined with 125I seed implantation and transarterial infusion chemotherapy for the treatment of pancreatic head cancer with obstructive jaundice. MethodFrom October 2012 to January 2018, 21 consecutive patients diagnosed with biliary obstruction caused by locally advanced, nonmetastatic pancreatic cancer with cytologically or histologically confirmed by biopsy were enrolled and receive treatment with intraluminal brachytherapy using 125I seed strand and CT-guided percutaneous radioactive seed implantation therapy. The procedure-related and radiation complications were assessed. The outcomes were measured in terms of stent patency, patient survival, complications related to the procedure. ResultOne of the 22 patients (4.5%, 1/22) with pancreatic head cancer failed to perform the above procedure because the guidewire was unable to pass through the obstruction segment. The remaining 21 patients (95.5%, 21/22) with pancreatic head cancer with obstructive jaundice were successfully placed with biliary stents and radioactive strips through drainage tubes. The median number of 125I seeds loaded was 15, ranging from 12 to 17. After the chemotherapy with gemcitabine and cisplatin, no adverse reaction of Grade Ⅲ ∼ Ⅳ occurred in all cases. Median stent patency was 12.50 months (95% CI: 10.26, 14.74). By May 2019, all 21 patients had died, with overall survival of 5.2–23.3 months, with a median survival of 13.20 months (95% CI: 10.96, 15.44). ConclusionPercutaneous 125I seed implantation combined with insertion of radioactive strips through the biliary stent has the characteristics of less trauma, fewer complications, simple operation, and so on. These procedures bring remission of obstructive jaundice combined with the increased survival for the treatment of obstructive jaundice caused by unresectable pancreatic head cancer if follow-up chemotherapy is carried out. The long-term efficacy of this treatment combination needs to be confirmed by further multicenter, large sample size prospective randomized controlled studies.

Transarterial infusion chemotherapy (TAI) combined with Sintilimab in locally advanced, potentially resectable hepatocellular carcinoma (HCC).

e16593 Background: Our previous studies showed that TAI with modified FOLFOX increased tumor response and resection rate compared with conventional TACE in advanced HCC. PD-1/PD-L1 inhibitors have been demonstrated promising value in HCC. This study aims to evaluate the efficacy and safety of FOLFOX-TAI combined with Sintilimab (a PD-1 inhibitor) in locally advanced, potentially resectable HCC. Methods: This prospective, nonrandomized controlled phase II study is recruiting 40 pts with locally advanced, potentially resectable HCC (localized to semi-liver with invasion to branch of the portal vein). Pts in the combined group receive repeated 3-week cycles of Sintilimab 200mg IV Day1 and TAI with FOLFOX Day2 (Oxaliplatin 130 mg/m2, Leucovorin 400 mg/m2, 5-FU 400 mg/m2 and 5-FU 2400 mg/m2, next 46 hours). Pts in the control group only received TAI. Tumor assessment with RECIST 1.1 was performed every 2 cycles. The pts gained visible tumor shrinkage and opportunity for resection received surgical hepatectomy. Pts with stable disease (SD) or unconfirmed progression disease (PD) will receive repeated cycles until confirmed PD or intolerable toxicity, with max cycles of 8 for TAI and 16 for Sintilimab. The primary endpoint is progression or postoperative relapse free survival (PFS). Secondary endpoints include ORR, DCR, resection rate, OS, and safety. Results: As of Jan 10, 2020, 33 eligible pts were enrolled. All treatment related AEs were grade 1 or 2, including transaminase and bilirubin increase, nausea, hypoalbuminemia, rash, leucopenia, thrombopenia, and weight loss. No irAE and treatment related SAE was observed. Conclusions: TAI combined with Sintilimab attributed to high surgical conversion rate and good safety profile for locally advanced, potentially resectable HCC. Clinical trial information: NCT03869034 .

Postoperative adjuvant transarterial infusion chemotherapy with FOLFOX could improve outcomes of hepatocellular carcinoma patients with microvascular invasion: A preliminary report of a phase III, randomized, controlled clinical trial.

527 Background: Microvascular invasion (MVI) is a risk factor for recurrence after hepatectomy for hepatocellular carcinoma (HCC) patients. This study aimed to investigate to efficacy and safety of postoperative adjuvant transarterial infusion chemotherapy (TAI) with FOLFOX regimen for HCC patients with MVI. Methods: In this prospective, phase III, randomized, open-labeled, controlled clinical trial, HCC patients with histologically confirmed MVI were randomly assigned (1:1) after hepatectomy to receive either 1-2 cycles adjuvant TAI (AT group) or follow-up without any adjuvant treatment (FU group). The primary endpoint was disease-free survival (DFS), the secondary endpoints are overall survival (OS) and safety. Results: Between June, 2016 and April 2019, 127 patients were randomly assigned to AT group (n=63) or FU group (n=64). Clinicopathological characteristics were balanced between the two groups. The 6-, 12-, and 18-month OS rates for AT group were 100.0%, 97.7%, and 97.7%, and were 94.5%, 89.6%, and 78.5% for FU group, respectively. The 6-, 12-, and 18-month DFS rates for AT group were 84.7%, 61.8%, and 58.7%, and were 62.9%, 48.1%, and 38.6% for FU group, respectively. The OS and DFS were significantly better in AT group than in FU group (p=0.037 and 0.023, respectively). No patients in AT group experienced grade 3 or more severe adverse events (AEs). Conclusions: Adjuvant TAI after hepatectomy may bring survival benefits of OS and DFS for HCC patients with MVI. Clinical trial information: NCT03192618.

Acute kidney injury after platinum-based transcatheter arterial chemoembolization and transarterial infusion chemotherapy in patients with hepatocellular carcinoma.

The incidence of acute kidney injury and the association between acute kidney injury and prognosis have been reported about transcatheter arterial chemoembolization using anthracycline. However, the incidence of acute kidney injury after platinum-based transarterial chemoembolization or transarterial infusion chemotherapy remains unclear. The aim of this study was to investigate association between acute kidney injury after platinum-based transcatheter arterial chemoembolization/transarterial infusion chemotherapy and prognosis in patients with hepatocellular carcinoma. We retrospectively analysed 270 sessions in 129 patients who underwent platinum-based transcatheter arterial chemoembolization/transarterial infusion chemotherapy. Acute kidney injury was diagnosed according to the criteria established by the International Club of Ascites. The incidence of acute kidney injury, risk factors for serum creatinine elevation and association between acute kidney injury and prognosis were assessed. Fifteen cases of acute kidney injury (5.6%, 15/270) developed in 14 patients (10.8%, 14/129). Ascites (coefficient: 0.059, P=0.006), low estimated glomerular filtration rate (coefficient: -0.008, P=0.029), diabetes (coefficient: 0.072, P<0.001) and high albumin-bilirubin grade (albumin-bilirubin grade 2: coefficient: 0.053, P=0.004; and albumin-bilirubin grade 3: coefficient: 0.103, P<0.001) were significantly associated with an elevation in serum creatinine levels after transcatheter arterial chemoembolization/transarterial infusion chemotherapy. The development of acute kidney injury was associated with poor prognosis (hazard ratio: 3.18, 95%CI: 1.411-7.171, P=0.005). Patients with acute kidney injury had a significantly lower survival rate than patients without acute kidney injury (log-rank test; P=0.034). The incidence of acute kidney injury after platinum-based transcatheter arterial chemoembolization/transarterial infusion chemotherapy was consistent with that after transcatheter arterial chemoembolization using anthracycline, and the development of acute kidney injury was associated with poor prognosis. Ascites, diabetes, low estimated glomerular filtration rate and high albumin-bilirubin grade were risk factors for serum creatinine elevation after platinum-based transcatheter arterial chemoembolization/transarterial infusion chemotherapy.

Transarterial Infusion Chemotherapy with FOLFOX for Advanced Hepatocellular Carcinoma: A Multi-Center Propensity Score Matched Analysis of Real-World Practice

Background: To compare the treatment effectiveness and safety among transarterial infusion chemotherapy (TAI) with FOLFOX regimen, transarterial chemoembolization (TACE), and sorafenib in patients with BCLC stage C hepatocellular carcinoma (HCC). Methods: The data of consecutive patients with BCLC stage C HCC treated with TAI, TACE, or sorafenib from January 2015 to December 2018 at three centers were retrospectively analyzed. Propensity-score matched (PSM) analysis was pairwise performed (TAI vs. TACE and TAI vs. sorafenib) to reduce selection bias. Treatment effectiveness and safety were evaluated and compared using the Kaplan-Meier method, log-rank test, Cox regression models, and I‡2 test. Findings: The median overall survival (OS) in the matched TAI group was significantly longer than the sorafenib group (19*6 months vs. 7*5 months, p=0*009), and the TACE group (estimated 27*8 months vs. 6*6 months, p<0*001). The difference in median progression-free survival (PFS) between the matched TAI and sorafenib groups was not significant (5*8 months vs. 2*3 months, p=0*219). The median PFS in the matched TAI group was significantly longer than the TACE group (6*5 months vs. 2*8 months, p<0*001). The objective response rate (ORR) in the matched TAI group was significantly higher than the sorafenib group (36*4% vs. 0*0%, p<0*001) and the TACE group (48*7% vs. 4*7%, p<0*001). The incidences of adverse events (AEs) were similar among these three groups. Interpretation: TAI with FOLFOX regimen was an effective and safe therapy that improved survival of patients with BCLC stage C HCC. Funding Statement: This study was supported by the National Natural Science Foundation of China (No. 81871985); Natural Science Foundation of Guangdong Province (No. 2018A0303130098 and No. 2017A030310203); Medical Scientific Research Foundation of Guangdong Province (No. A2017477); Science and Technology Planning Project of Guangzhou (No. 201903010017 and No. 201904010479); Clinical Trials Project (5010 Project) of Sun Yat-sen University (No. 5010-2017009). Declaration of Interests: All authors declared no conflicts of interest. Ethics Approval Statement: This study was conducted according to the ethical guidelines of the 1975 Declaration of Helsinki, and it was reviewed and approved by the Institutional Review Board at the Sun Yat-sen University Cancer Center (No. B2018-126-01). Informed consent was obtained from each patient for the data to be used for research.

Angiographic Findings in Patients with Hepatocellular Carcinoma Previously Treated Using Proton Beam Therapy.

Given the growing interest in using proton beam therapy (PBT) for hepatocellular carcinoma (HCC), it is possible that transarterial chemoembolization (TACE) could be used for selected patients who have previously undergone PBT. However, these cases can be technically challenging to treat and require appropriate preparation. Thus, we aimed to identify angiographic findings in this setting. We retrospectively identified 31 patients (28 men and 3 women, mean age: 69 years, range: 43–84 years) who underwent hepatic angiography plus TACE or transarterial infusion chemotherapy (TAI) for HCC that recurred after PBT (July 2007 to June 2018). We discovered four angiographic findings, which we speculate were related to the previous PBT. 18 patients experienced recurrence in the irradiated field, and 13 patients experienced recurrence outside the irradiated field. 29 patients underwent TACE and only 2 patients underwent TAI. The mean number of previous PBT treatments was 1.3 ± 0.6 (range: 1–4). The median interval from the earliest PBT treatment to hepatic angiography was 559 days (range: 34–5,383 days), and the median interval from the latest PBT treatment to hepatic angiography was 464 days (range: 34–5,383 days). Abnormal staining of the irradiated liver parenchyma was observed in 22 patients, which obscured the angiographic tumor staining in 4 patients. Development of a tortuous tumor feeder vessel was observed in 13 patients. Development of an extrahepatic collateral pathway was observed in 7 patients. Development of an arterioportal or arteriovenous shunt was observed in 4 patients. Based on these findings, we conclude that PBT was associated with various angiographic findings during subsequent transarterial chemotherapy for recurrent HCC, and familiarity with these findings will be important in developing appropriate treatment plans.

Effect of Interventional Therapy on the Expression of Survivin mRNA in Cervical Cancer

To examine the expression of survivin mRNA in cervical squamous cancer at different time points during interventional therapy in order to find the optimal time point for continual treatment. Fifty patients with stage IB2-IIB cervical squamous cancer receiving transarterial infusion chemotherapy and chemoembolization were included in the present study. The expression of survivin mRNA in cancer samples before and after interventional therapy (on days 7, 14 and 21) were examined by reverse transcription-polymerase chain reaction. The expression of survivin mRNA in cancer samples before the interventional therapy was significantly higher than that of any time point after the interventional therapy (p<0.05). After treatment, the expression of survivin mRNA decreased until day 14. The expression of survivin mRNA was inhibited by the interventional therapy. It seems that day 14 after interventional treatment is the right time point for continuation of treatment.

Transarterial chemoembolization for management of hemoptysis: initial experience in advanced primary lung cancer patients.

To evaluate the hemostatic effects of transarterial infusion chemotherapy in addition to embolization (chemoembolization) for advanced primary lung cancer with tumor-related hemoptysis. Ten consecutive patients with stage IIIB/IV or recurrent primary lung cancer (squamous cell carcinoma in six, adenocarcinoma in four) who underwent chemoembolization for control of hemoptysis were enrolled. At enrollment, five patients were considered refractory and five had contraindications to standard therapies. The amount of hemoptysis was massive in two patients, moderate in seven, and slight in one. Transarterial infusion chemotherapy via feeding arteries using cisplatin (25mg/m2) and 5-fluorouracil (300mg/m2) was repeated every 3-4weeks for three cycles. HepaSphere (100-150µm) or gelatin sponge particles were selected as embolic materials depending on the presence of pulmonary shunts and were added for embolization just after drug infusion. Hemoptysis improved in all patients (resolution in nine, significant decrease in one). The median hemostasis time was 11.9months (range 2.7-25.9months). The target pulmonary lesions shrank in seven patients, and pulmonary atelectasis disappeared in three of five patients. Chemoembolization may be a palliative option with favorable hemostasis time for advanced primary lung cancer with hemoptysis.

Early Decreases in α-Fetoprotein and Des-γ-carboxy Prothrombin Predict the Antitumor Effects of Hepatic Transarterial Infusion Chemotherapy with Cisplatin (CDDP) Powder in Patients with Advanced Hepatocellular Carcinoma.

Objective We retrospectively investigated the relationship between the tumor response and serial changes in α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) during hepatic arterial infusion of a cisplatin powder formulation (CDDP powder) in patients with advanced hepatocellular carcinoma (HCC). Methods Seventy-six advanced HCC patients were analyzed. All HCC patients received high-concentration cisplatin (1.43 mg/mL) via the haptic artery at a dose of 65 mg/m(2). AFP and DCP were measured at baseline and four to eight weeks after treatment, and the antitumor responses were evaluated according to the response evaluation criteria in solid tumours (RECIST) criteria after one or two courses of treatment. The patients were classified into two groups, a decreased group and a non-decreased group, according to the change in the serum levels of AFP and DCP at four to eight weeks compared to baseline. Results The response to treatment of the decreased group (n=16) and non-decreased group (n=60) was complete response/partial response/stable disease/progressive disease (CR/PR/SD/PD) in 4/4/5/3 and 1/11/8/40 patients, respectively. The response rate and disease control rate of the decreased group were significantly higher than those of the non-decreased group (p=0.016 and p<0.001, respectively). The median survival time (MST) of the decreased/non-decreased groups were 25.9/10.6 months, respectively. The cumulative survival rates for the decreased group were significantly higher than those of the non-decreased group (p=0.042). In the multivariate analysis, vascular invasion and the decreased group were significant factors that affected the therapeutic efficacy. Conclusion A decrease in the levels of AFP and DCP after the first treatment with CDDP powder is a good predictor for the antitumor effect and the prognosis.

Rapid and early α-fetoprotein and des-γ-carboxy prothrombin responses to initial arterial infusion chemotherapy predict treatment outcomes of advanced hepatocellular carcinoma.

The aim of the present study was to predict the effects of transarterial infusion (TAI) chemotherapy based on early changes in α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) in patients with advanced hepatocellular carcinoma (HCC). Seventy-four patients who underwent TAI with cisplatin, 5-fluorouracil, mitomycin C and epirubicin for advanced HCC were enrolled. Antitumor responses were evaluated 6 months after TAI. Rapid and early responses were defined as the ratio of AFP or DCP after 1 week and 1 month compared to baseline. A total of 5, 10, 17 and 42 patients had complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD), respectively. Early AFP response was significantly lower in the CR+PR compared to the SD+PD groups (P<0.01). The early DCP response was significantly lower in the CR+PR compared to the SD+PD. The sensitivity and specificity of rapid and early AFP responses in the CR+PR were 0.78 and 0.72, and 0.80 and 0.73, respectively, and those of rapid and early DCP responses were 0.67 and 0.65, and 0.77 and 0.71, respectively. The combination of AFP and DCP responses had higher specificity compared to AFP or DCP alone responses. Patients were divided into responder and non-responder groups to evaluate the prediction of survival outcome. Early responders of AFP, DCP and AFP+DCP, who were divided based on the cut-off values of CR+PR survived significantly longer than the non-responders (P<0.05). In conclusion, rapid or early responses of AFP and/or DCP levels 1 and 4 weeks after TAI chemotherapy helped to predict the treatment effects.