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Introduction: Local therapies for high risk non-muscle-invasive bladder cancer (NMIBC) such as intravesical chemotherapy (IVC) have shown a high rate of progression and recurrence (1). Intravesical Bacillus Calmette-Guérin (BCG) for local therapies has been shown to reduce progression and recurrence in patient with NMIBC. However, its potential role is limited in high burden countries for tuberculosis (TB) due to its low specificity that can cause wrong diagnosis or false positive in patients with clinically diagnosed tuberculosis. BCG vaccine that has to be given for most people in tuberculosis endemic countries will induce trained immunity that could reduce the effectivity of intravesical BCG for NMIBC Moreover, intravesical BCG is contraindicated in patient with or previous tuberculosis. The potential clinical benefit of intraarterial chemotherapy (IAC) in delaying the recurrence and progression of high-risk NMIBC have been investigated with promising results (2, 3). We aimed to conduct a meta-analysis to evaluate the potential anti-tumor effect of IAC in NMIBC. Methods: We conducted a comprehensive search of published articles in Cochrane Library, Pubmed, and Science-Direct to identify relevant randomized controlled trials (RCTs) and observational studies comparing IAC alone or combined with IVC versus IVC/BCG alone in NMIBC. The protocol of preferred reporting items for systematic review and meta-analysis (PRISMA) was applied to this study. Results: Four RCTs and 4 cohort observational studies were eligible in this study and 5 studies were included in meta-analysis. The risk ratio of tumor recurrence was reduced by 35% (RR = 0.65; 95% CI 0.49-0.87; p = 0.004) in IAC plus IVC, while recurrence-free survival (RFS) was prolonged by 45% (HR: 0.55; 95% CI, 0.44-0.69; p < 0.001). The risk of tumor progression was reduced by 45% (RR = 0.55; 95% CI 0.41-0.75; p = 0.002) and tumor progression-free survival (PFS) was also prolonged by 53% (HR: 0.47; 95% CI, 0.34-0.65; p < 0.001). Some RCT's had high or unclear risk of bias, meanwhile 4 included cohort studies had overall low risk of bias, therefore the pooled results need to be interpreted cautiously. Subgroup analysis revealed that the heterogeneity outcome of tumour recurrence might be attributed to the difference in NMIBC stages and grades. Conclusions: The IAC alone or combined with IVC following bladder tumor resection may lower the risk of tumor recurrence and progression. These findings highlight the importance of further multi institutional randomized controlled trials with bigger sample size using a standardized IAC protocol to validate the current results. [ABSTRACT FROM AUTHOR]

Introduction: Local therapies for high risk non-muscle-invasive bladder cancer (NMIBC) such as intravesical chemotherapy (IVC) have shown a high rate of progression and recurrence (1). Intravesical Bacillus Calmette-Guérin (BCG) for local therapies has been shown to reduce progression and recurrence in patient with NMIBC. However, its potential role is limited in high burden countries for tuberculosis (TB) due to its low specificity that can cause wrong diagnosis or false positive in patients with clinically diagnosed tuberculosis. BCG vaccine that has to be given for most people in tuberculosis endemic countries will induce trained immunity that could reduce the effectivity of intravesical BCG for NMIBC Moreover, intravesical BCG is contraindicated in patient with or previous tuberculosis. The potential clinical benefit of intraarterial chemotherapy (IAC) in delaying the recurrence and progression of high-risk NMIBC have been investigated with promising results (2, 3). We aimed to conduct a meta-analysis to evaluate the potential anti-tumor effect of IAC in NMIBC. Methods: We conducted a comprehensive search of published articles in Cochrane Library, Pubmed, and Science-Direct to identify relevant randomized controlled trials (RCTs) and observational studies comparing IAC alone or combined with IVC versus IVC/BCG alone in NMIBC. The protocol of preferred reporting items for systematic review and meta-analysis (PRISMA) was applied to this study. Results: Four RCTs and 4 cohort observational studies were eligible in this study and 5 studies were included in meta-analysis. The risk ratio of tumor recurrence was reduced by 35% (RR = 0.65; 95% CI 0.49-0.87; p = 0.004) in IAC plus IVC, while recurrence-free survival (RFS) was prolonged by 45% (HR: 0.55; 95% CI, 0.44-0.69; p < 0.001). The risk of tumor progression was reduced by 45% (RR = 0.55; 95% CI 0.41-0.75; p = 0.002) and tumor progression-free survival (PFS) was also prolonged by 53% (HR: 0.47; 95% CI, 0.34-0.65; p < 0.001). Some RCT’s had high or unclear risk of bias, meanwhile 4 included cohort studies had overall low risk of bias, therefore the pooled results need to be interpreted cautiously. Subgroup analysis revealed that the heterogeneity outcome of tumour recurrence might be attributed to the difference in NMIBC stages and grades. Conclusions: The IAC alone or combined with IVC following bladder tumor resection may lower the risk of tumor recurrence A systematic review and meta-analysis of intraarterial chemotherapy for non muscle invasive bladder cancer: Promising alternative therapy in high tuberculosis burden countries Zakaria Aulia Rahman 1, 2, Furqan Hidayatullah 1, 2, Jasmine Lim3, Lukman Hakim1, 4 1 Department of Urology, Faculty of Medicine, Universitas Airlangga; 2 Dr. Soetomo General-Academic Hospital, Surabaya, East Java, Indonesia; 3 Department of Surgery, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 4 Universitas Airlangga Teaching Hospital, Surabaya, East Java, Indonesia. DOI: 10.4081/aiua.2024.12154 Summary and progression. These findings highlight the importance of further multi institutional randomized controlled trials with bigger sample size using a standardized IAC protocol to validate the current results.

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Purpose : The goal of this study was to compare the efficacy of intraarterial chemotherapy (IAC) for retinoblastoma delivered via the ophthalmic artery (OA) division of the internal carotid artery (ICA) versus alternative branches of the external carotid artery (ECA). Methods: We performed a retrospective chart review of patients receiving IAC for retinoblastoma at a single institution. Subjects were divided into three groups: those that received IAC solely through the OA branch of the ICA, those that initially received IAC through the OA branch of the ICA but were later switched to the ECA, and those that only received IAC through the ECA. The main outcomes compared included globe salvage rate and reduction in tumor thickness and size. Results: A total of 30 eyes from 26 patients were included. A total of 91 (58%) sessions of IAC were performed through the OA division of the ICA and 65 (42%) were performed through branches of the ECA. Eleven eyes (37%) solely received IAC through the OA branch of the ICA, 16 eyes (53%) were converted to ECA treatment, and 3 eyes solely received IAC through branches of the ECA. Statistical analysis did not show any significant difference in globe salvage rate or reduction in tumor thickness and size. Conclusion: The use of alternative approaches for IAC when the OA branch of the ICA catheterization is not feasible allows for safe continued delivery of highly effective IAC, leading to similar outcomes in terms of globe salvage and reduction in tumor size. [ABSTRACT FROM AUTHOR]

Retinoblatoma is now the pediatric cancer with the highest cure rate. More than any other ocular malignancy the approach to this cancer has changed dramatically in the past 10 years. Most of the things taught to the majority of all Ophthalmology residents is out of date. Because few Ophthalmologists deal with retinoblastoma they are not aware of these seismic changes so this summary of my Curtin lectures outlines some of the major changes all Ophthalmologists should be familiar with. [ABSTRACT FROM AUTHOR]

Background In pursuit of a cure for cancer, it is imperative to utilize every tool, resource, and strategy. Included under this umbrella is the optimization of drug delivery. Broadly speaking, anti‐cancer treatment has been perpetually hindered by off‐target activity, systemic toxicity, and other adverse reactions. Intraarterial (IA) delivery of therapeutics is an approach that has garnered increased attention in recent years. This approach can deliver drug directly to the desired site with the potential to minimize systemic toxicity. Methods In this review, we briefly cover existing IA indications for peripheral solid tumors as a base from which we can learn, followed by trials and procedural considerations of IA drug delivery for neck, head, and central nervous system tumors. Results While the bulk of IA research and clinical trials have focused on drug delivery outside of the central nervous system, there have been recent encouraging results in IA tumor treatment within the neurointerventional arena, such as head and neck tumors, retinoblastoma, glioblastoma multiforme, and central nervous system lymphoma. Conclusion This review highlights the need for increased clinical research on IA chemotherapeutic delivery as a multi‐disciplinary approach involving neurointerventional surgeons.

Cell-free DNA analysis in cancer has gone from research to widespread clinical use in the past 10 years. At Memorial Sloan Kettering Cancer Center, we developed a technology and test to assay cell-free DNA (cfDNA) from blood (plasma) in our retinoblastoma patients. cfDNA derived from intraocular retinoblastoma can be measured and quantified in the blood (plasma) of patients. It is derived from the tumor cells themselves. Simulating lesions did not have cfDNA abnormalities. cfDNA disappears quickly after cutting the optic nerve (50% gone in 10 minutes) and if cfDNA is measurable after enucleation, metastases develop. Analysis of the buffy coat can detect germline defects including very low levels of mosaicism not detected with other NGS techniques. Analysis of the buffy coat also reveals non Rb1 germline predilections to second cancers. Analysis of cfDNA from blood of retinoblastoma patients can be used to diagnose and manage retinoblastoma and reflect an accurate molecular profile of RB1 abnormalities of the intraocular tumor. Analysis of the germline with the buffy coat detects very low levels of mosaicism not detected with conventional methods. Liquid biopsy for retinoblastoma is already in clinical use and offers information not available with any other technique. [ABSTRACT FROM AUTHOR]

Background: Patients with unresectable recurrent rectal cancer (RRC) or colorectal cancer (CRC) with liver metastases, refractory to at least two lines of traditional systemic therapy, may receive third line intraarterial chemotherapy (IC) and targeted therapy (TT) using drugs selected by chemosensitivity and tumor gene expression analyses of liquid biopsy-derived circulating tumor cells (CTCs).Methods: In this retrospective study, 36 patients with refractory unresectable RRC or refractory unresectable CRC liver metastases were submitted for IC and TT with agents selected by precision oncotherapy chemosensitivity assays performed on liquid biopsy-derived CTCs, transiently cultured in vitro, and by tumor gene expression in the same CTC population, as a ratio to tumor gene expression in peripheral mononuclear blood cells (PMBCs) from the same individual. The endpoint was to evaluate the predictive accuracy of a specific liquid biopsy precision oncotherapy CTC purification and in vitro culture methodology for a positive RECIST 1.1 response to the therapy selected.Results: Our analyses resulted in evaluations of 94.12% (95% CI 0.71-0.99) for sensitivity, 5.26% (95% CI 0.01-0.26) for specificity, a predictive value of 47.06% (95% CI 0.29-0.65) for a positive response, a predictive value of 50% (95% CI 0.01-0.98) for a negative response, with an overall calculated predictive accuracy of 47.22% (95% CI 0.30-0.64).Conclusions: This is the first reported estimation of predictive accuracy derived from combining chemosensitivity and tumor gene expression analyses on liquid biopsy-derived CTCs, transiently cultured in vitro which, despite limitations, represents a baseline and benchmark which we envisage will be improve upon by methodological and technological advances and future clinical trials. [ABSTRACT FROM AUTHOR]

Objective: Human papilloma virus-negative oropharyngeal cancer has not achieved satisfactory outcomes compared with those of human papilloma virus-positive oropharyngeal cancer. This study evaluated the therapeutic efficacy of selective intraarterial chemoradiotherapy with the docetaxel and nedaplatin regimen for human papilloma virus-negative oropharyngeal cancer.Methods: Twenty-two consecutive patients with human papilloma virus-negative oropharyngeal cancer who had undergone selective intraarterial chemoradiotherapy were retrospectively analyzed. The primary tumor and whole neck were irradiated (50 Gy). Subsequently, the primary site and metastatic lymph nodes were boosted by 20 Gy. The intraarterial chemotherapy regimen comprised a combination of nedaplatin (80 mg/m2) and docetaxel (60 mg/m2), which was initially administered at the start of radiotherapy and was given every 4 weeks for three sessions. Each intraarterial dose of an anticancer agent was determined according to the percentage of the tumor volume supplied by the target artery to the total tumor volume, which was intraoperatively measured via cone-beam computed tomography. The outcome measures were locoregional control, disease-free survival, and overall survival rates and adverse events. Statistical analyses were performed using the Kaplan-Meier method.Results: The median follow-up period was 59 (range, 15-103) months. The T stage was T1/T2 in 5 patients (23%), T3 in 5 patients (23%), and T4 in 12 patients (54%). Cervical lymph node metastasis was staged as ≥N2c in 7 (32%) patients. Complete response was achieved in all patients at the first imaging examination after intraarterial chemoradiotherapy. The 5-year locoregional control, disease-free survival, and overall survival rates were 96% (95% confidence interval, 0.72-0.99), 91% (95% confidence interval, 0.68-0.98), and 100% (95% confidence interval, not available), respectively. Regarding serious acute adverse events, grade 4 laryngeal edema and leukopenia were observed in 1 (5%) and 11 patients (50%), respectively. No other serious acute adverse events were observed.Conclusion: Selective intraarterial chemoradiotherapy with docetaxel and nedaplatin has the potential to achieve favorable locoregional control, disease-free survival, and overall survival rates in human papilloma virus-negative oropharyngeal cancer. [ABSTRACT FROM AUTHOR]

We report one retinoblastoma patient with dual ophthalmic arteries (also known as "double ophthalmic arteries") arising from the internal carotid artery which fuse with each other inside the orbit. The caudal ophthalmic artery with larger caliber originated from the cavernous segment of internal carotid artery and passed through the superior orbital fissure. The cranial and tiny one arose more cranially from the supraclinoid internal carotid artery and passed through the optic canal. After superselective catheterization, frank anastomosis was shown between two ophthalmic arteries and the central retinal artery arose from the cranial one. To the best of our knowledge, this case is the first observation of a dual ophthalmic artery with cavernous/supracavernous origins fusing with each other proven by superselective ophthalmic angiography. Whether there is an anastomosis between two ophthalmic arteries is important for deciding which artery to be selected for intraarterial treatment. In cases of retinoblastoma, detailed angiographic analysis may be essential to examine the orbital arterial system and to avoid unexpected complications during intraarterial chemotherapy. [ABSTRACT FROM AUTHOR]

Retinoblastoma stands as a paradigm of success in treating malignancies among pediatric patients. Over recent decades, the approach to managing retinoblastoma has evolved significantly, transitioning from the preservation of patients' lives to the preservation of eyes and vision while minimizing treatment-related complications. Chemotherapy, administered through diverse routes, has solidified its role as the cornerstone of retinoblastoma treatment. In addition to intravenous chemotherapy (IVC), alternative administration routes, including intraarterial (IAC), intravitreal, intracameral, and periocular delivery, have emerged as promising modalities for retinoblastoma management. Numerous studies have demonstrated outstanding outcomes, achieving nearly 100% salvage rates for eyes classified under groups A-C. However, for advanced intraocular retinoblastoma (groups D and E eyes), IAC appears to offer superior local control rates compared to IVC. Intravitreal injection of chemotherapeutic agents, when administered in a controlled and secure manner, holds promise in averting the need for enucleation and radiotherapy in advanced retinoblastoma cases presenting with vitreous seeds. The optimal chemotherapy strategy remains meticulously tailored based on numerous factors. This review provides a comprehensive update on chemotherapy across various routes, encompassing key considerations, dosages, administration methods, treatment outcomes, and potential complications. Furthermore, it explores emerging potential treatments and outlines future directions aimed at enhancing treatment outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate magnetic resonance imaging (MRI) findings in patients suffering choroidal occlusive vasculopathy (COV) after intra-arterial chemotherapy (IAC) for retinoblastoma., Methods: A retrospective study of 37 eyes of 34 patients receiving IAQ between 2016 to 2021 as primary or secondary treatment for retinoblastoma was conducted. Twenty-two patients received systemic chemotherapy with carboplatin, vincristine and etoposide. The rest received IAC as primary treatment. The drugs administered were melphalan (3-4mg), carboplatin (40mg) plus topotecan (20mg). The patients were examined under general anaesthesia every month to observe tumor regression and possible complications of the treatment. For the patients with COV an MRI was obtained to analyse the choroidal thickness and axial ocular length., Results: A COV was observed in 5 of the 37 eyes receiving IAC (13,51%), all of them with a complete sectorial choroidopathy not sparing the fovea (grade 2). In 4 of the 5 patients the choroidal thickness was decreased and in three cases the size of the eye which presented COV was clearly smaller than the contralateral eye. Tumor control was archived in all 5 patients., Conclusion: In our cases COV was associated with reduction of thinning of choroid and eye length in the MRI. A new classification maybe needed to correlate better with the severity of the complication affecting the fovea. Although early results generally are favorable to the use of IAC, longer follow up and scrupulous documentation of side effects will be necessary to know the true role of IAC for retinoblastoma., (Copyright © 2022 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)