Intra-arterial Chemotherapy Research Articles

Outcome of salvage intra-arterial chemotherapy for recurrent retinoblastoma.

To examine the outcome of salvage intra-arterial chemotherapy (IAC) for patients with recurrent retinoblastoma after the initial course of IAC and determine the factors influencing clinical outcome. A total of 73 eyes of 71 patients with recurrent retinoblastoma undergoing salvage IAC after initial successfully IAC between May 2014 and May 2019 were retrospectively reviewed for clinical outcomes. Ocular survival and progression-free survival were used to examine the efficacy of salvage IAC. The factors influencing clinical outcomes were determined using univariate and multivariate analyses. The salvage IAC was delivered at mean 9.4 months (median 7, range 2.1-38.3 months) following the last cycle of initial IAC. 86.5% (64/73) eyes relapsed 16 months after the initial IAC. After the salvage IAC, 57 eyes (78.1%) were salvaged, and no further-line therapies were required for 36 eyes (49.3%). The 2-year Kaplan-Meier ocular survival and progression-free survival estimates after salvage IAC were 66.4% (95% CI, 31.5-42.1%) and 38.2% (95% CI, 17.8-28.8%), respectively. Univariate and multivariate analyses showed that the ocular survival and progression-free survival after salvage IAC were significantly associated with the history of vitreous seeds (p = 0.02 and p = 0.03, respectively). Salvage IAC is effective for the management of recurrent retinoblastoma after the initial successful IAC. Eyes with a history of vitreous seeds in the course of the disease are more likely to relapse and with worse ocular survival. A close follow-up strategy is imperative to treat the recurrent tumour after salvage IAC.

Trial working groups for paediatric brain tumours

Abstract Aims Children's brain tumours are the biggest cancer killer in children and young adults. Several recent developments have the potential to change the treatment of brain tumours in children. These include intra-CSF chemotherapy, ultrasound-mediated blood-brain barrier disruption, convection enhanced delivery, polymer delivery systems and electric field therapy, as well as intra-arterial and intra-nasal chemotherapy. To date, there have been very few clinical trials to evaluate any of these. The science and technology underlying these developments is not traditionally embedded within the standard paediatric neuro-oncology network. In addition, custom-built hardware, novel surgical procedures and, in some cases, the testing and licensing of implantable devices, add difficulty at the regulatory level. Method The authors participated in an international workshop funded by the charity Children with Cancer UK in 2016, where different experimental techniques aimed at optimising CNS drug delivery were discussed. Following this workshop and two subsequent workshops run by the CBTDDC (Children’s Brain Tumour Drug Delivery Consortium) in 2018 and 2020, the CBTDDC and the recently developed ITCC (Innovative Therapies for Children with Cancer) brain tumour group started working together to set up a new initiative. Called the ‘Clinical Trials Working Group for Central Nervous System Drug Delivery’, this aims to accelerate clinical trials to assess the safety and effectiveness of drug delivery devices for the treatment of paediatric brain tumours. On March 1st, 2021, CBTDDC with guest chair, Mr Kristian Aquilina (Consultant Paediatric Neurosurgeon at Great Ormond Street Hospital), hosted the first virtual meeting of this group. Results We have assembled a prestigious steering group, comprising international researchers and clinicians with expertise in diverse aspects of translational and clinical research in CNS drug delivery. At our first group meeting on March 1st, 2021, 38 leading brain tumour research scientists and clinicians from the UK, EU and US tackled the challenges head-on, with commitment and a driving passion to identify and move forwards with the most effective ways of translating drug delivery modalities into clinical trials. Attendees were split into three break-out sessions based on distinct drug delivery systems, and lots of insightful comments were collated. Conclusion The ideas generated during the 1st March meeting will help form the basis of a CBTDDC ‘Clinical Trials’ workshop in the autumn of 2021. In particular, there was an agreed consensus that a key objective will be the creation of a ‘Roadmap’ document for pre-clinical to clinical translation which would be shared with the paediatric neuro-oncology research community. CBTDDC look forward to working with steering group as we act on their recommendations to address the current challenges faced by translational drug delivery research. We present this abstract to the BNOS Annual 2021 Meeting to raise awareness of this initiative with the large number of relevant stakeholders who will be attending the event.

Targeted Neoadjuvant Intra-arterial Chemotherapy in Lacrimal Gland Adenoid Cystic Carcinoma: A Histological Correlation Using Apoptotic Tumor Markers.

Neoadjuvant intra-arterial cytoreductive chemotherapy is used for the treatment of lacrimal gland adenoid cystic carcinomas (ACC) to improve outcomes in this condition with an otherwise dismal prognosis. We share our experience in the management of an advanced case of ACC using a novel, highly targeted intra-arterial cytoreductive chemotherapy delivery technique involving both the internal and external carotid circulation, with an attempt to correlate the effect histologically. Refinement of the chemotherapy delivery using the tumor's vascular anatomy and appropriate blood vessel selection may lead to future globe sparing procedures without compromising survival.

Therapeutic efficacy of selective intra-arterial chemoradiotherapy with docetaxel and nedaplatin for fixed bulky nodal disease in head and neck cancer of unknown primary.

Fixed bulky nodal disease in patients with head and neck cancer of unknown primary (HNCUP) remains difficult to treat. This retrospective study evaluated the therapeutic efficacy of selective intra-arterial chemoradiotherapy with docetaxel and nedaplatin for fixed bulky nodal disease in HNCUP. Data from seven consecutive patients with fixed bulky nodal disease in HNCUP who had undergone selective intra-arterial chemoradiotherapy were analyzed. Whole pharyngeal mucosa and all bilateral nodal areas were irradiated (total dose 50Gy), and bulky nodal lesions were provided an additional 20Gy. Intra-arterial chemotherapy used a combination of nedaplatin (80mg/m2) and docetaxel (60mg/m2). Outcome measures were local control, disease-free survival, overall survival, and adverse events. Statistical analyses were performed using the Kaplan-Meier method. Median follow-up period was 24months (range 9-64). All patients had extracapsular extension (N3b) on imaging and clinical findings. Symptoms due to bulky disease were neck discomfort (100%), tumor bleeding (43%), tracheal obstruction (14%), and carotid sinus syndrome (28%). Median value for maximum diameter of cervical disease was 84mm (range 70-107), and 3-year local control, disease-free survival, and overall survival rates were 100, 54, and 64%, respectively. Symptoms due to bulky disease disappeared in all patients after intra-arterial chemoradiotherapy. Grade 4 leukopenia occurred in two patients (28%) as an acute adverse event. No other serious acute adverse events were observed. Selective intra-arterial chemoradiotherapy with docetaxel and nedaplatin can potentially achieve both favorable local control and survival in in HNCUP with fixed bulky nodal disease.

Результаты хирургии катаракты у детей с ретинобластомой

Purpose. To present results of cataract surgery in children with retinoblastoma. Material and methods. Within the period from 2012 to 2020, cataract surgery was performed in 21 children (22 eyes) with retinoblastoma aged 28 to 155 months (average – 65 months). Tumors of group B occurred in 2 cases, group C – in 4, group D – in 14, group E – in 1. In 8 cases, cataract occurred in a single eye. Posterior capsular cataract was observed in 18 patients, total – in 3. In all cases, the presence of cataract impeded the control of the tumor. Before cataract surgery all children underwent systemic chemotherapy, some of them also underwent intra-arterial and/or intravitreal chemotherapy, external beam radiotherapy, Gamma Knife stereotactic radiosurgery and local treatment modalities (episcleral plaque brachytherapy, thermotherapy, cryotherapy). There were no signs of tumor progression in all cases at the time of cataract surgery. The mean interval between complete tumor regression and cataract surgery was 23 months (range 6–75 months). Results. Full transparency of optical media was achieved in all eyes after surgery. No intraoperative and postoperative complications occurred. The final visual acuity was improved in 12 eyes, in the rest visual acuity could not be determined due to age. There were no signs of tumor recurrence or metastases in mean follow-up after surgery of 29 months (range 3–60). Conclusion. Our experience of cataract surgery in children with complete regression of retinoblastoma was proved to be a safe and effective way to improve visual functions and achieve transparency of optical media. Key words: retinoblastoma, cataract surgery, ophtalmooncology, functional results

Contemporary Update of Retinoblastoma in China: Three-Decade Changes in Epidemiology, Clinical Features, Treatments, and Outcomes

To report three-decade changes of clinical characteristics, progress of treatments, and risk factors associated with mortality and enucleation in patients with retinoblastoma in China. Retrospective cohort study. This multicenter study included 2552 patients diagnosed with retinoblastoma in 38 medical centers in 31 provinces in China from 1989 to 2017, with follow-up data. Kendall's tau-b value was used to describe correlation coefficients between the three eras (between 1989 and 2008, between 2009 and 2013, and between 2014 and 2017) and clinical or demographic features. Hazard ratios and odds ratios were applied to measure risk factors. A total of 324 (13%) patients died and 1414 (42%) eyes were removed. The 1-year, 3-year, and 5-year overall survival rates were 95%, 86%, and 83%, respectively. Patients were diagnosed at a better stage by International Classification for Retinoblastoma over time (Kendall's tau-b value=-0.084, P < .001). Pathological risk factors were also observed less in recent eras. New conservative therapies were adopted and used in more patients. The eye removal rate gradually decreased (Kendall's tau-b value=-0.167, P < .001). The overall survival rates were 81%, 83%, and 91% in the three eras. By multivariate Cox regression, bilateral tumors and extraocular extension were identified as risk factors for death. Among intraocular disease, Group E indicated higher risk of mortality. By multivariate logistics regression, unilateral tumors, earlier era of diagnosis, and extraocular extension were risk factors for eye salvage failure. Among intraocular retinoblastoma, Groups D and E had higher risk of eye salvage failure. Patients were diagnosed at an earlier stage in recent eras. Conservative therapies, including intra-arterial chemotherapy, were increasingly being used. The above changes may contribute to the decreasing enucleation rate. Although no significant impact was identified on the mortality by the three eras, a decreasing trend was shown.

Clinical Outcomes of Intra-arterial Chemoradiotherapy and Neoadjuvant Chemoradiotherapy Followed by Surgery for Maxillary Sinus Squamous Cell Carcinoma

Background: Although intra-arterial chemoradiotherapy (CRT) followed by surgery has been the standard of care for patients with advanced maxillary sinus squamous cell carcinoma (MSSCC), concurrent intra-arterial chemotherapy and high-dose radiotherapy without surgery has emerged as a promising alternative. Objectives: This study aimed to evaluate the ability of intra-arterial CRT alone to increase the overall survival (OS) of patients with MSSCC. Patients and Methods: Forty patients with histologically confirmed MSSCC, who were treated at Tokyo Medical University Hospital (Tokyo, Japan) between February 1999 and June 2015, were enrolled in this study. Twenty-seven patients were treated with intra-arterial CRT (median dose of 60 Gy) without surgery (CRT group), whereas 13 patients were treated with neoadjuvant intra-arterial CRT (median dose of 40 Gy), followed by surgery (S group). The association of OS with age, performance status, T factor (mean tumor size according to the tumor-node-metastasis [TNM] grading system), N factor (mean lymph node involvement according to the TNM grading system), and treatment method was assessed. Results: The median follow-up duration was 36.0 months. There were no significant differences regarding the patients’ characteristics between the two groups. The treatment method was the only significant prognostic factor for OS. The five-year OS rates were 92% and 55% in the CRT and S groups, respectively (P = 0.01). Conclusion: The intra-arterial CRT (60 Gy) without surgery yielded improved survival outcomes in patients with advanced MSSCC as compared to the neoadjuvant intra-arterial CRT (40 Gy) followed by surgery.

Five-Year Experience in Treatment of Retinoblastoma with Intra-Arterial Chemotherapy: A Single-Center Analysis.

Purpose:To report our 5-year experience in treating retinoblastoma (RB) with intra-arterial chemotherapy (IAC) as a primary or secondary therapy, without adjuvant intravitreal chemotherapy.Methods:A retrospective study was conducted on 70 eyes with intraocular RB that were treated with primary or secondary IAC from December 2010-2015. Demographic characteristics, clinical features, tumor control, and treatment complications were compared and reported.Results:Thirty-seven eyes had received IAC as a secondary therapy after failed/incomplete response to systemic chemotherapy, and 33 eyes had received IAC as a primary treatment. The mean age of patients was 25 ± 8.9 months, and the patients were followed for a mean of 24.5 ± 16.26 months. Overall, enucleation rates were significantly higher in advanced tumors (Group D and E) in both groups (both P < 0.05). The main reason for enucleation in this study group was being unresponsive to treatment (27.4%), with 76% of latter patients having vitreous seeds at the time of enucleation. Enucleation rates did not differ significantly between patients receiving primary (18/33, 54%) or secondary IAC (18/37, 48%) (P = 0.06). In addition, recurrence and complication rates did not differ significantly between eyes receiving IAC as their primary or secondary treatment (P > 0.05).Conclusion:In primary and secondary treatment of RB with IAC, the main findings that are globe salvage, recurrence, and complication rates were comparable when no adjuvant intravitreal chemotherapy was used.

Application of intra-arterial chemotherapy in high-risk non-muscle invasive bladder cancer: a systematic review and meta-analysis.

BackgroundTo summarize the current evidence on the effects of intra-arterial chemotherapy (IAC) on high-risk non-muscle invasive bladder cancer (NMIBC) and compare oncology results with intravesical chemotherapy (IVC).MethodsWe performed a systematic review and cumulative meta-analysis of the primary outcomes of interest by a systematical search of multiple scientific databases in February 2021. The mean difference (MD) and odds ratio (OR) were calculated for continuous and dichotomous variables respectively, with 95% confidence intervals (CIs). The hazard radio (HR) with 95% CIs was used for overall survival (OS), recurrence-free survival (RFS) and progression-free survival (PFS).ResultsA total of six studies with 866 patients were included. For IAC combined with IVC versus IVC alone, statistically significant differences were found regarding tumor recurrence rate (OR: 0.51, 95% CI [0.36∼0.72], p = 0.0001), tumor progression rate (OR: 0.47, 95% CI [0.30∼0.72], p = 0.0006), tumor-specific death rate (OR: 0.49, 95% CI [0.25∼0.99], p = 0.05), PFS (HR: 0.47, 95% CI [0.23∼0.96], p = 0.04) and RFS (HR: 0.60, 95% CI [0.41∼0.87], p = 0.007). No significant difference between two groups was found for time to first recurrence (MD: 3.27, 95% CI [−2.37∼8.92], p = 0.26) and OS (HR: 1.20, 95% CI [0.44∼3.32], p = 0.72). For IAC alone versus IVC, There was no statistical difference in the terms of tumor-specific death rate (OR: 0.67, 95% CI [0.29∼1.53], p = 0.34), RFS (HR: 0.90, 95% CI [0.56∼1.46], p = 0.68) and PFS (HR: 0.71, 95% CI [0.32∼1.55], p = 0.39). Adverse events mainly included nausea/vomiting (36.3%), hypoleukemia (19.4%), neutropenia (16.0%), increased creatinine (9.9%), increased alanine aminotransferase (18.7%), and thrombocytopenia (9.9%).ConclusionThe IAC combined with IVC is a safe and effective treatment for high risk NMIBC, with lower rates of recurrence, progression, tumor-specific death, PFS and RFS, and with minor and tolerable events. The effectiveness of the IAC alone is parallel to the IVC alone.

Application of Jianpi Xiaoai Recipe Combined with Cisplatin and Adriamycin in the Treatment of Endometrial Cancer and Its Effect on Disease Control Rate.

Objective To explore the application of Jianpi Xiaoai recipe combined with cisplatin and Adriamycin in the treatment of endometrial cancer (EC) and its effect on the disease control rate (DCR). Methods The data of 120 EC patients treated in People's Hospital of Rizhao from February 2019 to February 2020 were retrospectively analyzed. They were equally split into experimental group and control group according to the order of admission. All patients were treated with neoadjuvant intra-arterial chemotherapy (continuous infusion of the uterine artery for 5 days before surgery, with 20 mg of cisplatin mixed with 2000 mg of normal saline and 10 mg of Adriamycin mixed with 500 ml of normal saline daily), while the experimental group was treated with Jianpi Xiaoai recipe at the same time to compare the short-term efficacy, immune function indexes, incidence of adverse reactions, and HEC-1-B (human endometrial adenocarcinoma cells) cell inhibition rates between the two groups. Results The DCR and objective remission rate (ORR) in the experimental group were markedly higher compared with the control group (P < 0.05). The immune function indexes after treatment were remarkably better in the experimental group than in the control group (P < 0.05). Compared with the control group, the incidence of adverse reactions in the experimental group was notably lower (P < 0.05), while the HEC-1-B inhibition rates after treatment were obviously higher (P < 0.05). Conclusion Jianpi Xiaoai recipe combined with cisplatin and Adriamycin can increase the HEC-1-B cell inhibition rate in EC patients, improve their immune function, reduce the possibility of adverse reactions, and enhance the therapeutic effect, which is worthy of clinical application and popularization.

CLRM-08. TRIAL WORKING GROUPS FOR PAEDIATRIC BRAIN TUMOURS

INTRODUCTIONBrain tumours are the biggest cancer killer in children and young adults. Several recent developments have the potential to change the outlook for these children, including intra-CSF chemotherapy, ultrasound-mediated blood-brain barrier disruption, convection enhanced delivery, polymer delivery systems, electric field therapy, and intra-arterial and intra-nasal chemotherapy. To date, there have been very few clinical trials to evaluate these. In addition, custom-built hardware, novel surgical procedures and the testing and licensing of implantable devices add difficulty at the regulatory level.METHODSThe authors participated in an international workshop funded by the charity Children with Cancer UK in 2016, where different experimental techniques aimed at optimising CNS drug delivery were discussed. Following this and two subsequent workshops run by the CBTDDC (Children’s Brain Tumour Drug Delivery Consortium), the CBTDDC and the ITCC (Innovative Therapies for Children with Cancer) brain tumour group launched the ‘Clinical Trials Working Group for Central Nervous System Drug Delivery’. This aims to accelerate clinical trials to assess the safety and effectiveness of drug delivery devices for the treatment of paediatric brain tumours.RESULTSOn 1 March, 2021, CBTDDC and Mr Kristian Aquilina (Consultant Paediatric Neurosurgeon at Great Ormond Street Hospital) hosted the first steering group meeting, comprising 38 leading brain tumour research scientists and clinicians from the UK, EU and US.CONCLUSIONThe ideas generated during the March meeting are driving the agenda for a Clinical Trials Workshop that will be held in the autumn of 2021. In particular, there was agreed consensus that a ‘Roadmap’ document for pre-clinical to clinical translation needs to be created and shared with the paediatric neuro-oncology research community. We present this abstract to the CNS Clinical Trials Meeting to raise awareness of this initiative with the large number of relevant stakeholders who will be attending the event.

Orbital Retinoblastoma Treated with Intra-arterial Chemotherapy

A 5-year-old boy was referred with local orbital extension of unilateral retinoblastoma (Fig A) and measurable plasma cell-free RB1 DNA (Fig B, magnetic resonance imaging [MRI]). Two years prior he had received 2 courses of systemic chemotherapy with Carboplatin, Vincristine and Etoposide but additional treatment was halted because of a war in his country. Thirteen months later, after 3 sessions of ophthalmic artery chemosurgery with Melphalan, Carboplatin, and Topotecan at our institution, there was complete resolution of the tumor (Fig C) and disappearance of cfDNA (Fig D, MRI).

Efficacy of Intra-Arterial Plus Intravesical Chemotherapy for High-Risk Non-Muscle-Invasive Bladder Cancer: A Pooled Analysis.

Background: The treatment for high-risk non-muscle-invasive bladder cancer (NMIBC) remains highly debated for its high recurrence and progression risk. This work aimed to verify the efficacy and toxicity of intra-arterial chemotherapy (IAC) plus intravesical chemotherapy (IVC) in high-risk NMIBC.Methods: A comprehensive online literature search was conducted in three databases to select researches related to IAC + IVC for high-risk NMIBC. All data were analyzed using the Review Manager software version 5.3. And we used the Cochrane Risk of Bias tool to assessed the quality of these enrolled researches.Results: Seven eligible original publications were enrolled in our studies with a total of 1,247 patients. Compared with the intravesical instillation, IAC + IVC therapy showed a better therapeutic effect. The total odds ratio for tumor recurrence rate, tumor progression rate, survival rate, and tumor-specific death rate was calculated as 0.51 (95% CI: 0.36–0.72; p < 0.05), 0.51 (95% CI: 0.36–0.72; p < 0.05), 1.75 (95% CI: 1.09–2.81; p < 0.05), and 0.48 (95% CI: 0.28–0.84; p < 0.05), respectively. In patients who received IAC, most of the adverse events (AEs)in the treatment were Grade I and II.Conclusion: IAC + IVC regimen for high-risk NMIBC could effectively reduce recurrence and progression and provide a better prognosis than intravesical instillation. The adverse events of IAC were mild and acceptable.

Resident Perspectives 56-5

Resident Perspectives 56-5

"Unifocality as Prognostic Factor for Unilateral Retinoblastoma: Preliminary Results of 32 Eyes Treated with Intra-Arterial Chemotherapy Alone"

Retinoblastoma (RB) is the most common intraocular malignancy of in childhood. Approximately 60% of cases are unilateral while 40% are bilateral...

P14.88 Management of primary CNS lymphomas. Experience of 32 cases

Abstract BACKGROUND Lymphomas (primary and secondary) are rare tumors of the central nervous system. They can involve both the supratentorial areas and the posterior cranial fossa. Modern management of patients with suspected CNS lymphoma should include a stereotactic or navigation-guided biopsy and subsequently carrying out chemotherapy and, in rare cases, radiosurgery. MATERIAL AND METHODS We analyzed our experience of the diagnosis and treatment of PCNSL. Our work included 32 patients with PCNSL. The study did not include patients with suspected CNS lymphoma, according to MRI data, in whom the diagnosis was not confirmed after biopsy. RESULTS Thirty patients underwent biopsy (20 - navigation guided, 1 - open, 9 - “burr hole”) with preliminary intraoperative histological verification. Gross total resection was performed in 2 cases since, according to preoperative MRI data, it was assumed that the patient had glial tumors. Postoperative histological examination confirmed the diagnosis of CNS lymphoma in all cases. Subsequently, after detailed histological and immunohistochemical studies, 30 patients underwent intra-arterial chemotherapy or high-dose chemotherapy according to NCCN protocols. Palliative treatment was recommended in 2 cases due to acute deterioration of patients. In our work, we would like to present a diagnostic algorithm and treatment regimens used in the management of our patients. CONCLUSION In the treatment of CNS lymphomas, careful histological verification is required, which is possible if several key points are performed - discontinuation of dexamethasone at least 24 hours before the biopsy, MRI for intraoperative neuronavigation after discontinuation of dexamethasone, intraoperative preliminary histological verification. In our opinion, complete removal of the tumor is possible if there are no risks of developing a persistent neurological deficit. Various methods of opening the blood-brain barrier are currently used, which can significantly reduce the effective dosage of drugs and, accordingly, the side effects. Further research is needed to determine the dependence of the prognosis of the disease on the type of surgery (biopsy or resection).

Efficacy, Toxicity, and Pharmacokinetics of Intra-Arterial Chemotherapy Versus Intravenous Chemotherapy for Retinoblastoma in Animal Models and Patients.

PurposeThrough controlled comparative rabbit experiments and parallel patient studies, our purpose was to understand mechanisms underlying differences in efficacy and toxicity between intra-arterial chemotherapy (IAC) and intravenous chemotherapy (IVC).MethodsIn rabbits, ocular tissue drug levels were measured following IAC and IVC. Retinal toxicity was assessed using electroretinography, fluorescein angiography, optical coherence tomography (OCT) and OCT angiography. Efficacy to eradicate retinoblastoma orthotopic xenografts was compared. In IAC and IVC patients, we measured blood carboplatin pharmacokinetics and compared efficacy and toxicity.ResultsIn rabbits receiving IAC, maximum carboplatin levels were 134 times greater in retina (P = 0.01) and 411 times greater in vitreous (P < 0.001), and total carboplatin (area under the curve) was 123 times greater in retina (P = 0.005) and 131 times greater in vitreous (P = 0.02) compared with IVC. Melphalan levels were 12 times greater (P = 0.003) in retina and 26 times greater in vitreous (P < 0.001) for IAC. Blood levels were not different. IAC melphalan (but not IV melphalan or IV carboplatin, etoposide, and vincristine) caused widespread apoptosis in retinoblastoma xenografts but no functional retinal toxicity or cytopenias. In patients, blood levels following IVC were greater (P < 0.001) but, when adjusted for treatment dose, were not statistically different. Per treatment cycle in patients, IVC caused higher rates of anemia (0.32 ± 0.29 vs. 0.01 ± 0.04; P = 0.0086), thrombocytopenia (0.5 ± 0.42 vs. 0.0 ± 0.0; P = 0.0042), and neutropenia (0.58 ± 0.3 vs. 0.31 ± 0.25; P = 0.032) but lower treatment success rates (P = 0.0017).ConclusionsThe greater efficacy and lower systemic toxicity with IAC appear to be attributable to the greater ocular-to-systemic drug concentration ratio compared with IVC.Translational RelevanceProvides an overarching hypothesis for a mechanism of efficacy/toxicity to guide future drug development.

RB1 Circulating Tumor DNA in the Blood of Patients with Unilateral Retinoblastoma: Before and after Intra-arterial Chemotherapy

PurposeCirculating tumor DNA (ctDNA) is released by many tumors into the plasma. Its analysis has minimal procedural risk and, in many cancers, has the potential for clinical applications. In retinoblastoma, the clinical correlations of ctDNA in eyes treated without enucleation have not been studied. This purpose of this study was to determine how the ctDNA RB1 variant allele frequency (VAF) changes in patients with unilateral retinoblastoma after intra-arterial chemotherapy (IAC) treatment. Variant allele frequency is a proxy for tumor fraction.DesignCase series from a single tertiary cancer referral center.ParticipantsFive patients with retinoblastoma with at least 1 measurable ctDNA plasma specimen both at the time of active intraocular retinoblastoma before IAC and after at least 1 IAC cycle.MethodsCirculating tumor DNA RB1 was detected and VAF was measured before and after IAC treatment. Clinical correlations were made using clinical examination, fundus photography, ultrasound, and OCT.Main Outcome MeasuresComparison of ctDNA RB1 VAF before and after IAC treatment for retinoblastoma and concordance of ctDNA RB1 detectability with activity of intraocular disease.ResultsTwenty-three ctDNA specimens were included from 5 patients. The 5 baseline RB1 VAFs ranged from 0.27% to 4.23%. In all patients, the subsequent post–intra-arterial RB1 VAF was lower than baseline (0.0%–0.17%). At 4 months (2 months after IAC completion), the ctDNA consistently was negative in the patients who demonstrated clinically inactive intraocular disease.ConclusionsIn this small cohort, a decremental decrease in ctDNA RB1 VAF was found after IAC, suggesting that relative VAF changes could be a biomarker of treatment response.

Aqueous seeding in intraocular retinoblastoma: A review.

The management of retinoblastoma is complex. With increasing treatment modalities and increasing experience with each treatment modality, the globe salvage rates have drastically improved with time. Aqueous seeding in an eye with retinoblastoma is classified as group E based on International Classification of Intraocular Retinoblastoma, and most group E eyes were enucleated a decade earlier. Newer modalities of treatment have improved the globe salvage rates in group E eyes including those with aqueous seeding. Various globe salvage treatment modalities attempted for the management of aqueous seeds include external beam radiotherapy, plaque radiotherapy, intra-arterial chemotherapy, periocular chemotherapy, intravitreal chemotherapy and intracameral chemotherapy. Of all treatment modalities, intracameral chemotherapy holds promise for the management of aqueous seeds in selected patients, but it should be done with the utmost care by a trained ocular oncologist. Enucleation is still the preferred modality of treatment for eyes with advanced retinoblastoma and anterior segment invasion. This review focuses on the current evidence on aqueous seeding, highlighting the pathogenesis, classification, clinical presentation, treatment and outcomes.

Intraarterial Chemotherapy for Retinoblastoma - Initial Experiences of a German Reference Centre.

Adequate management of retinoblastoma requires a multidisciplinary and individual approach to treatment. Intraarterial chemotherapy (IAC) is one of the most commonly used treatment modalities, and enables supraselective application of chemotherapy via the ophthalmic artery and is now established in almost all treatment centres. However, published treatment success rates are heterogeneous. There are some unanswered issues regarding sight-threatening ocular complications and the long-term occurrence of secondary malignancies and metastatic disease. The objective of the present study is to analyse the results of a German national reference centre. Retrospective analysis of all children with an indication for at least one IAC from April 2010 to April 2020. IAC was used either as primary or recurrence therapy. Obligatory follow-up was at least 6 months. 137 eyes of 127 children with an indication for IAC could be included. 12 eyes with a follow-up of less than 6 months and 37 eyes in which IAC was technically not feasible were excluded. In summary, 88 eyes of 79 children were finally analysed. Mean follow-up was 38 months, ranging from 7 to 117 months. In total, 195 procedures were completed. In 30 eyes (34.1%) IAC was conducted as primary and in 58 (65.9%) as secondary therapy. There was an initial IAC treatment response in 75 eyes (85.2%) with a recurrence-free rate of 61.3%. Eye salvage rate was 68.1% with 28 enucleated eyes in total. Ocular complications were observed in 36 eyes (40.9%), with 19 eyes (21.6%) showing severe sight-threatening and 11 eyes (12.5%) presenting minor non-sight-threatening toxic reactions. During follow-up, 1 child developed a secondary malignancy, 1 child developed metastasis and 1 child died as a consequence of trilateral retinoblastoma. In summary, IAC is a potent modality for retinoblastoma treatment and has been very successful, even in advanced disease and heavily pretreated eyes. However, ocular complications should be taken in consideration, especially when the only seeing eye is treated. Long term incidences of secondary malignancies and metastatic diseases should be further investigated in prospective studies.