Combined intra-arterial chemotherapy and intravitreal melphalan for the treatment of advanced unilateral retinoblastoma

●AIM:To evaluate the efficacy and safety of combined intraarterial chemotherapy(IAC)and intravitreal melphalan(IVM)for the treatment of advanced unilateral retinoblastoma.●METHODS:This retrospective study involved 30 consecutive eyes from 30 Chinese patients with advanced unilateral retinoblastoma.All patients were initially treated with IAC combined with IVM.The clinical status and complications were recorded at each visit.●RESULTS:The International Intraocular Retinoblastoma Classification groups were D in 23 eyes and E in 7 eyes.All eyes showed severe cloud vitreous seeds at the first visit.The mean number of IAC cycles and intravitreal injections was 3.2(range,3-4)and 6(range,1-14),respectively.The median follow-up time was 29 mo(range,7-36 mo).Treatment success with regression of the retinal tumor and vitreous seeds was achieved in 29 of 30 eyes(96.7%).Globe salvage was attained in 93.3%(28/30)eyes,and enucleation(n=2)was per formed due to neovascular glaucoma and persistent vitreous hemorrhage.Complications included retinal pigment epithelium(RPE)atrophy(n=13;43%),mild lens opacity(n=7;23%),vitreous hemorrhage(n=5;17%)and rhegmatogenous retinal detachment(n=1;3%).No extraocular tumor extension or metastasis occurred.●CONCLUSION:Combined IAC and IVM is effective and safe for the treatment of advanced unilateral retinoblastoma.

Use of intra-arterial chemotherapy for retinoblastoma:results of a survey

·AIM: To obtain baseline knowledge about the current use of intra-arterial chemotherapy(SSOAIC) in centers worldwide.·METHODS: A survey including questions about the use of SSOAIC was emailed to retinoblastoma experts.·RESULTS:Seventy-nine(response rate 69.9%) doctors from 63 centers in 35 countries responded. Thirty-one centers from 19 countries use SSOAIC. Twelve performed more than 50 procedures. Melphalan is the most commonly used drug but 15 centers use more than one drug. First line therapy for advanced unilateral disease is the most common use of SSOAIC(74.2%). Centers with larger experience(】50 applications) were less likely using melphalan alone(P =0.06) and significantly more likely using SSOAIC in more situations such as second line in preference to radiotherapy P =0.05. Nineteen(61.2%)stated that SSOAIC improved their results and 21(77.8%)reported less toxicity compared to other treatments.Three centers reported that SSOAIC did not improve their results. There were regional variations in the use of SSOAIC which is used more frequently as secondary treatment in Europe compared to the USA and Japan.Ten centers identified cost is the major limiting factor for SSOAIC.· CONCLUSION: SSOAIC is used in an increasing number of centers worldwide with regional variations.Centers with more experience in SSOAIC use it in more situations including other drugs than melphalan. The majority of the centers using this technique reportedimproved results and few complications.

Efficacy of second-course intra-arterial chemotherapy in children for advanced retinoblastoma recurrence after intra-arterial chemotherapy

Purpose: The present study determined the efficacy and toxicity of second-course intra-arterial chemotherapy(IAC) in advanced retinoblastoma(RB) recurrence in children following failed initial IAC. Materials and Methods: A total of 24 child patients with unilateral or bilateral intra-ocular advanced RB(IIRC Group D and Group E) undergoing second-course IAC treatment after initial intra-arterial chemotherapy between September 2011 and November 2016 were enrolled. Global salvage, ocular adverse events, and systemic adverse events were assessed. Results: Following second-course IAC, 15(62.5%) showed complete control at 34 months follow-up, while 8 cases(33.3%) failed the treatment and 1 patient with metastatic disease(4.2%) eventually died of brain metastasis after refusing treatment. Ocular adverse events included eyelid edema(n=12), ptosis(n=5), forehead erythema(n-5), enophthalmos(n=3), and cataract(n=2). None of the patients had systemic adverse events, such as stroke or sepsis. Also, no secondary neoplasms and technical complications were observed. Conclusion: Second-course IAC is a potential alternative to enucleation in children with advanced RB, who fail an initial course of IAC. However, patients with advanced RB should be managed at experienced centers in order to consider all the alternatives before enucleation.

Prognostic value of post-treatment ^(18)F-FDG PET/CT for advanced head and neck cancer after combined intra-arterial chemotherapy and radiotherapy

Objective：To clarify the prognostic value of post-treatment 18F-fluorodeoxyglucose （FDG） positron emission tomography （PET）/computed tomography （CT） in patients with advanced head and neck squamous cell carcinoma （HNSCC） after combined intra-arterial chemotherapy and radiotherapy （IACR）.Methods：Thirty-six patients with HNSCC who underwent IACR were recruited.The period from the end of IACR to the last post-treatment 18F-FDG PET/CT examination was 8-12 weeks.Both patient-based and lesion-based analyses were used to evaluate the PET/CT images.For lesion-based analysis,36 regions （12 lesions of recurrences and 24 scars at primary sites） were selected.The Kaplan-Meier method was used to assess the overall survival （OS） stratified by 18F-FDG uptake or visual interpretation results.Results：Twelve patients with recurrence were identified by six months after IACR.The sensitivity and specificity in the patient-based analysis were 67％ （8/12） and 88％ （21/24）,respectively.The mean OS was estimated to be 12.1 months （95％ CI,6.3-18.0 months） for the higher maximum standardized uptake value （SUVmax） group （n=7） and 44.6 months （95％ CI,39.9-49.3 months） for the lower SUVmax group （n=29）.OS in the higher SUVmax group （cut-off point,6.1） or positive visual interpretation group was significantly shorter than that in the lower SUVmax or negative visual interpretation group （P＜0.001 and P＜0.05,respectively）.Conclusions：The SUVmax and visual interpretation of HNSCC on post-IACR 18F-FDG PET/CT can provide prognostic survival estimates.

HIGH DOSE INTRA-ARTERIAL HEPATIC INFUSIONAL CHEMOTHERAPY WITH DRUG FILTRATION (HAI-F) FOR PRIMARY LIVER CANCER(A PRELIMINARY REPORT)

Fifteen patients with unresectable hepatocellular carcinoma were treated with unresectable hepatocellular carcinoma were treated with high dose MMC or ADR via hepatic artery with drug filtration in our hospital from April to December 1988. Among them, 11 cases (73%) had symptoms relief, 3 cases (20%) tumor minimal remission and AFP decreased in 4 cases (33%). One case dide of hep'atoma 8 months after HAI-F and another case was followed up only 2 months after treatment, the remaining 13 cases are alive for 5 to 10 months after HAI-F. The reasons of unsatisfactory results were analyzed and possible ways of improvement were suggested.

Intra-Arterial Chemotherapy for Retinoblastoma

The management of retinoblastoma is challenging and complex. Preservation of the eyeball as well as vision, with minimum morbidity, is the aim in the initial stages. This has been made possible by the use of chemotherapy that is targeted to the eye in the form of selective intravitreal and intra-arterial chemotherapy which has shown promising results. The efficacy and safety of intra- arterial chemotherapy have been reported by many specialized centers. The aim of this article was to review the role of intraarterial chemotherapy in the management of retinoblastoma and its clinical outcomes. In addition, we will review the possible complications of the procedure. We were able to collect articles relevant to our research objectives by reviewing the title and abstract of each article. Irrelevant articles and those that did not meet the inclusion criteria were excluded. This yielded a total of 19 studies. The results indicated that intraarterial chemotherapy is an effective and new modality of treatment for retinoblastoma to salvage the eyeball and helps in the prevention of enucleation with minimal local and systemic complications that are mostly transient. For future work, we recommend conducting more prospective studies with large samples and the long duration of follow-up. Also, we recommend future studies focusing on assessing visual acuity, as most of the currently available studies did not assess the visual acuity, making the judgment on vision preservation with IAC difficult.

Efficacy of continuous gastric artery infusion chemotherapy in relieving digestive obstruction in advanced gastric cancer

BACKGROUND Obstruction or fullness after feeding is common in gastric cancer(GC)patients,affecting their nutritional status and quality of life.Patients with digestive obstruction are generally in a more advanced stage.Existing methods,including palliative gastrectomy,gastrojejunostomy,endoluminal stent,jejunal nutrition tube and intravenous chemotherapy,have limitations in treating these symptoms.AIM To analyze the efficacy of continuous gastric artery infusion chemotherapy(cGAIC)in relieving digestive obstruction in patients with advanced GC.METHODS This study was a retrospective study.Twenty-nine patients with digestive obstruction of advanced GC who underwent at least one cycle of treatment were reviewed at The Second Affiliated Hospital of Zhejiang University School of Medicine.The oxaliplatin-based intra-arterial infusion regimen was applied in all patients.Mild systemic chemotherapy was used in combination with local treatment.The clinical response was evaluated by contrast-enhanced computed tomography using Response Evaluation Criteria In Solid Tumors(RECIST)criteria.Digestive tract symptoms and toxic effects were analyzed regularly.A comparison of the Karnofsky Performance Status(KPS)score and Stooler’s Dysphagia Score before and after therapy was made.Univariate survival analysis and multivariate survival analysis were also performed to explore the key factors affecting patient survival.RESULTS All patients finished cGAIC successfully without microcatheter displacement,as confirmed by arteriography.The median follow-up time was 24 mo(95%CI:20.24-27.76 mo).The overall response rate was 89.7%after cGAIC according to the RECIST criteria.The postoperative Stooler’s Dysphagia Score was significantly improved.Twentytwo(75.9%)of the 29 patients experienced relief of digestive obstruction after the first two cycles,and 13(44.8%)initially unresectable patients were then considered radically resectable.The median overall survival time(mOS)was 16 mo(95%CI:9.32-22.68 mo).Patients who received radical surgery had a significantly longer mOS than other patients(P value<0.001).Multivariate Cox regression analysis indicated that radical resection after cGAIC,intravenous chemotherapy after cGAIC,and immunotherapy after cGAIC were independent predictors of mOS.None of the patients stopped treatment because of adverse events.CONCLUSION cGAIC was effective and safe in relieving digestive obstruction in advanced GC,and it could improve surgical conversion possibility and survival time.

Clinical Observation of Arteriovenous Combined Chemotherapy in Advanced Gastric Cancer

Objective:To analyze the therapeutic effect and influencing factors of arteriovenous combined chemotherapy in 39 patients with advanced gastric cancer,and to explore the choice of therapeutic strategy.Methods:In this group of patients,the sequence of combined use of arteriovenous chemotherapy was 2 cycles of arterial chemotherapy first,followed by 3~4 cycles of systemic intravenous chemotherapy,and then changed to traditional Chinese medicine,oral chemotherapeutic drugs or immunotherapy after stable disease.Results:Thirty-five patients achieved complete disappearance of symptoms,significant tumor reduction of 26%(PR:13/39),moderate tumor reduction of 51%,18 patients with tumor markers decreased by more than 50%,4 patients completely reduced to normal,half-year survival rate of 90%,1-year survival rate of 56%,3-year survival rate of 33%,5-year survival rate of 10%.Conclusion:The use of arteriovenous combined chemotherapy and embolization in patients with middle and advanced gastric cancer is not only feasible,but also less complications.It can enable some patients to achieve stage II surgical resection,reduce or delay the metastasis and recurrence of patients,improve the quality of life of patients and prolong the survival time.

Retrospective analysis of 56 patients with advanced gastric cancer treated with combination of intravenous and intra-arterial intensified neoadjuvant chemotherapy

Background Pre-operative chemotherapy has gained widespread interest while treating advanced gastric cancer in eastern countries. However, there is currently no established standard regimen for gastric cancer. The aim of this research was to explore the value of preoperative chemotherapy with a combination of intravenous and intra-arterial intensified chemotherapy in advanced .qastric cancer.

Effect of multiple-phase regional intra-arterial infusion chemotherapy on patients with resectable pancreatic head adenocarcinoma

Background Regional intra-arterial infusion chemotherapy （RIAC） has been more valuable to improve prognosis and quality of life of patients with inoperable pancreatic adenocarcinomas, and adjuvant RIAC plays an important role in prolonging survival and reducing risk of liver metastasis after radical resection of pancreatic cancer, but the effect of preoperative or multiple-phase RIAC （preoperative combined with postoperative RIAC） for resectable pancreatic cancers has not been investigated. In this prospective study, the effect of multiple-phase RIAC for patients with resectable pancreatic head adenocarcinoma was evaluated, and its safety and validity comparing with postoperative RIAC were also assessed. Methods Patients with resectable pancreatic head cancer were randomly assigned to two groups. Patients in group A （n=-50） were treated with new therapeutic mode of extended pancreaticoduodenectomy combined with multiple-phase RIAC, and those in group B （n=-50） were treated with extended pancreaticoduodenectomy combined with postoperative RIAC in the same period. The feasibility, compliance and efficiency of the new therapeutic mode were evaluated by tumor size, serum tumor markers, clinical benefit response （CBR）, surgical complications, mortality and toxicity of RIAC. The disease-free survival time, median survival time, incidence of liver metastasis, survival rate at 1, 2, 3 and 5 years were also observed. Life curves were generated by the Kaplan-Meier method. Results The pain relief rate and CBR in group A was 80% and 84% respectively. Serum tumor markers decreased obviously and tumors size decreased in 26% of patients after preoperative RIAC in group A. No more surgical complications, mortality or severe systemic side effects were observed in group A compared with group B. The incidence of liver metastasis in group A was 34% which was lower than 50% in group B. The disease-free survival time and median survival time in group A were 15.5 months and 18 months respectively. The 1-, 2-, 3- and 5-year survival rates were 54.87%, 34.94%, 24.51% and 12.25% respectively. There was no significant difference of survival time or survival rates between two groups. Conclusions Multiple-phase RIAC is effective in combined therapy of resectable pancreatic head carcinomas by enhancing inhibition of tumor growth and reduction of liver metastasis, without negative effect on patients＇ safety or surgical procedure.

术前区域动脉灌注生长抑素和化疗药物对结肠癌细胞增殖、凋亡和血管形成的影响

目的探讨术前区域动脉灌注生长抑素和化疗药物对细胞增殖、凋亡和血管形成的影响。方法结肠癌病人45例,随机分为A、B和C组,每组15例。A组为术前加入善宁的区域动脉灌注化疗组,B组为术前不加入善宁的区域动脉灌注化疗组,C组不采用区域动脉灌注化疗常规手术组。切除标本行MVD、VEGF、Ki67LI、ALI检察。结果A、B、C组MVD分别为12±8、25±17、26±16(P<0.05),VEGF表达分别为39、70、72,Ki67LI分别为8±4、11±6、16±7(P<0.05),ALI分别为4.3±0.5、2.2±0.6、1.5±0.6(P<0.05)。区域动脉灌注化疗对肿瘤增殖有抑制作用,并促进细胞凋亡,加入善宁可以加强上述作用外,对肿瘤血管形成具有抑制作用。结论术前区域动脉灌注化疗药物,可以提高结肠癌的疗效,生长抑素可以增强其抗肿瘤作用。

眼内期视网膜母细胞瘤动脉化疗进展

视网膜母细胞瘤(RB)是婴幼儿最常见的眼内恶性肿瘤。化疗是眼内期RB的主要治疗方法,有助于最大限度保留患儿眼球。动脉化疗即经动脉对RB进行化疗,是近年来兴起的新的方法,可有效避免静脉化疗的全身毒副作用。该文就RB动脉化疗进展进行了综述。

A clinical and long-term follow-up study of perioperative sequential triple therapy for gastric cancer

INTRODUCTIONAlthough the long-term postoperative survival rateof gastric cancer(GC) patients has been improvedsignificantly since the local dissection of lymph nodewas widely used in China,yet the low curativeresection rate and the high recurrence rate fromperitoneal and hepatic metastases hinder it fromfurther improvement.To alter the currentunsatisfactory status of GC treatment,a

Colorectal liver metastases:An update on multidisciplinary approach

Liver metastasis is the commonest form of distant metastasis in colorectal cancer.Selection criteria for surgery and liver-directed therapies have recently been extended.However,resectability remains poorly defined.Tumour biology is increasingly recognized as an important prognostic factor;hence molecular profiling has a growing role in risk stratification and management planning.Surgical resection is the only treatment modality for curative intent.The most appropriate surgical approach is yet to be established.The primary cancer and the hepatic metastasis can be removed simultaneously or in a two-step approach;these two strategies have comparable long-term outcomes.For patients with a limited future liver remnant,portal vein embolization,combined ablation and resection,and associating liver partition and portal vein ligation for staged hepatectomy have been advocated,and each has their pros and cons.The role of neoadjuvant and adjuvant chemotherapy is still debated.Targeted biological agents and loco-regional therapies(thermal ablation,intra-arterial chemo-or radio-embolization,and stereotactic radiotherapy) further improve the already favourable results.The recent debate about offering liver transplantation to highly selected patients needs validation from large clinical trials.Evidencebased protocols are missing,and therefore optimal management of hepatic metastasis should be personalized and determined by a multi-disciplinary team.

An international survey of classification and treatment choices for group D retinoblastoma

AIM： To determine which IIRC scheme was used by retinoblastoma centers worldwide and the percentage of D eyes treated primarily with enucleation versus globe salvaging therapies as well as to correlate trends in treatment choice to IIRC version used and geographic region. METHODS： An anonymized electronic survey was offered to 115 physicians at 39 retinoblastoma centers worldwide asking about IIRC classification schemes and treatment patterns used between 2008 and 2012. Participants were asked to record which version of the IIRC was used for classification, how many group D eyes were diagnosed, and how many eyes were treated with enucleation versus globe salvaging therapies. Averages of eyes per treatment modality were calculated and stratified by both IIRC version and geographic region. Statistical significance was determined by Chi-square, ANOVA and Kruskal-Wallis tests using Prism. RESULTS： The survey was completed by 29% of physicians invited to participate. Totally 1807 D eyes were diagnosed. Regarding IIRC system, 27% of centers used the Children＇s Hospital of Los Angeles （CHLA） version, 33% used the Children＇s Oncology Group （COG） version, 23% used the Philadelphia version, and 17% were unsure. The rate for primary enucleation varied between 0 and 100% and the mean was 29%. By IIRC version, primary enucleation rates were： Philadelphia, 8%; COG, 34%; and CHLA, 37%. By geographic region, primary enucleation rates were： Latin America, 57%; Asia, 40%; Europe, 36%; Africa, 10%, US, 8%; and Middle East, 8%. However, systemic chemoreduction was used more often than enucleation in all regions except Latin America with a mean of 57% per center （P〈0.0001）. CONCLUSION： Worldwide there is no consensus on which IIRC version is used, systemic chemoreduction was the most frequently used initial treatment during the study period followed by enucleation and primary treatment modality, especially enucleation, varied greatly with regards to IIRC version used and geographic region.