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Retinoblastoma is the most common pediatric ocular malignancy. It is triggered by a biallelic mutation in the RB1 gene or MYCN oncogene amplification. Retinoblastomas can be unilateral (60%–70%) or bilateral (30%–40%); bilateral tumors are always heritable and present at an earlier age as compared to unilateral ones (18–24 months vs. 36 months in India). High prevalence rates, delayed presentation, and inaccessibility to healthcare lead to worse outcomes in developing countries. The past few decades have seen a paradigm change in the treatment of retinoblastomas, shifting from enucleation and external beam radiotherapy to less aggressive modalities for eye salvage. Multimodality treatment is now the standard of care and includes intraarterial or intravenous chemotherapy along with focal consolidation therapies such as transpupillary thermotherapy, cryotherapy, and laser photocoagulation. Intravitreal and intracameral chemotherapy can help in controlling intraocular seeds. Advanced extraocular or metastatic tumors still have a poor prognosis. Genetic testing, counseling, and screening of at-risk family members must be incorporated as essential parts of management. A better understanding of the genetics and molecular basis of retinoblastoma has opened up the path for potential targeted therapy in the future. Novel recent advances such as liquid biopsy, prenatal diagnosis, prognostic biomarkers, tylectomy, and chemoplaque point to promising future directions.

Retinoblastoma is the most common pediatric ocular malignancy. It is triggered by a biallelic mutation in the RB1 gene or MYCN oncogene amplification. Retinoblastomas can be unilateral (60%–70%) or bilateral (30%–40%); bilateral tumors are always heritable and present at an earlier age as compared to unilateral ones (18–24 months vs. 36 months in India). High prevalence rates, delayed presentation, and inaccessibility to healthcare lead to worse outcomes in developing countries. The past few decades have seen a paradigm change in the treatment of retinoblastomas, shifting from enucleation and external beam radiotherapy to less aggressive modalities for eye salvage. Multimodality treatment is now the standard of care and includes intraarterial or intravenous chemotherapy along with focal consolidation therapies such as transpupillary thermotherapy, cryotherapy, and laser photocoagulation. Intravitreal and intracameral chemotherapy can help in controlling intraocular seeds. Advanced extraocular or metastatic tumors still have a poor prognosis. Genetic testing, counseling, and screening of at‑risk family members must be incorporated as essential parts of management. A better understanding of the genetics and molecular basis of retinoblastoma has opened up the path for potential targeted therapy in the future. Novel recent advances such as liquid biopsy, prenatal diagnosis, prognostic biomarkers, tylectomy, and chemoplaque point to promising future directions. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the adverse effects of selective intra-arterial chemotherapy (SIAC) on the eyes and optic nerves of retinoblastoma patients using magnetic resonance imaging (MRI). We aim to understand the post-SIAC changes in orbital and ocular structures and evaluate their impact on eye and optic nerve growth. Experienced radiologists analyzed MR images of retinoblastoma eyes treated with SIAC, comparing them to eyes treated with other eye-saving methods and healthy eyes. Results reveal common adverse effects like inflammation and vascular changes, along with significant ocular growth arrest and optic nerve atrophy in eyes treated with SIAC, especially in children treated ≤ 12 months of age. This study underscores the importance of careful consideration when utilizing SIAC, particularly in young patients, due to its potential negative effects on eye and optic nerve development. This retrospective multicenter study examines therapy-induced orbital and ocular MRI findings in retinoblastoma patients following selective intra-arterial chemotherapy (SIAC) and quantifies the impact of SIAC on ocular and optic nerve growth. Patients were selected based on medical chart review, with inclusion criteria requiring the availability of posttreatment MR imaging encompassing T2-weighted and T1-weighted images (pre- and post-intravenous gadolinium administration). Qualitative features and quantitative measurements were independently scored by experienced radiologists, with deep learning segmentation aiding total eye volume assessment. Eyes were categorized into three groups: eyes receiving SIAC (Rb-SIAC), eyes treated with other eye-saving methods (Rb-control), and healthy eyes. The most prevalent adverse effects post-SIAC were inflammatory and vascular features, with therapy-induced contrast enhancement observed in the intraorbital optic nerve segment in 6% of patients. Quantitative analysis revealed significant growth arrest in Rb-SIAC eyes, particularly when treatment commenced ≤ 12 months of age. Optic nerve atrophy was a significant complication in Rb-SIAC eyes. In conclusion, this study highlights the vascular and inflammatory adverse effects observed post-SIAC in retinoblastoma patients and demonstrates a negative impact on eye and optic nerve growth, particularly in children treated ≤ 12 months of age, providing crucial insights for clinical management and future research. [ABSTRACT FROM AUTHOR]

Purpose: The study was undertaken to look into the clinicodemographic profile, management, and clinical outcomes of advanced retinoblastoma at a tertiary care center. Methods: A prospective cohort study was conducted from Jan 2019 to Dec 2022. Forty-two patients of intraocular advanced retinoblastoma were assessed. The treatment protocol was formulated based on size, extension of tumor, and laterality. Primary outcome measure was response to the treatment in terms of regression of tumor and seeds and no evidence of recurrence after 12 month in enucleated eyes. Secondary outcome measures were complications like implant exposure, metastasis, and death associated with each treatment modality. Results: The mean age of the study group was 13 months. The most common presentation was leukocoria with diminished vision. Most of the patients had group E retinoblastoma (n = 40, 95%) as per the International Classification of Retinoblastoma. In 12 patients with group E retinoblastoma, primary enucleation was performed and in six patients, secondary enucleation was done, in which initially, globe salvage treatment was tried. In 30 patients, globe salvage treatment was attempted and we could manage to save 23 eyes. The most common treatment modality was intra-arterial chemotherapy using a triple-drug regimen. One patient developed intracranial spread and died due to systemic metastasis during the follow-up period. Conclusion: The current study showed that globe salvage is possible in advanced retinoblastoma if appropriate therapy is instituted depending upon the extent of the tumor and availability of latest treatment modalities. Intra-arterial chemotherapy using triple drugs can be offered as a first-line therapy in advanced unilateral retinoblastoma as it has been found to be very effective in the present study. [ABSTRACT FROM AUTHOR]

Retinoblastoma is the most common eye malignancy in children that if left untreated can invade intraocular structures, metastasize, and rarely lead to death. Traditionally treated with systemic chemotherapy, Intra-arterial chemotherapy is gaining popularity as it allows for the direct administration of chemotherapy through the ophthalmic artery, thus reducing systemic side effects. Intra-arterial chemotherapy procedures have evolved, with refinements to reduce risks and radiation exposure. Intra-arterial chemotherapy boasts an impressive technical success rate and one year ocular survival even amongst advanced cases. This review offers a thorough examination of the technique, indications, contraindications, outcomes, and alternative options for Intra-arterial chemotherapy. [ABSTRACT FROM AUTHOR]

Background: This case report aims to describe an adverse reaction following intra-arterial melphalan chemotherapy in a 48-year-old female patient with choroidal melanoma. The chemotherapy was part of a phase I clinical trial (MELCOM Study - ClinicalTrials.gov ID: NCT05893654), designed to evaluate its efficacy as a bridge to Ru-106 brachytherapy for treating large uveal melanomas. This is the first reported case of a cutaneous reaction to melphalan in an adult patient. Observations: Upon administration of melphalan, the patient developed an erythematous periorbital skin lesion three days post-treatment. The lesion evolved into a hyperchromic brownish macule that later disappeared spontaneously. Conclusions and Importance: While melphalan successfully reduced the tumor dimensions, making the patient eligible for subsequent Ru-106 brachytherapy, it led to a cutaneous reaction previously reported only in pediatric patients. Despite this aesthetic complication, the therapy was effective in tumor reduction, highlighting the need for further studies to assess the risk-benefit profile of intra-arterial melphalan chemotherapy in adult populations.

Background Lacrimal gland adenoid cystic carcinoma (LGACC) has historically been associated with a poor prognosis even with localized disease, with a survival of 56% at 5 years. In 1988, we treated the first patient with neoadjuvant intra-arterial cytoreductive chemotherapy (IACC). Since then, we have used this protocol as the standard approach. We aim to analyze the outcomes of patients with LGACC treated with the protocol and compare them to a population-based cohort to assess if IACC can improve survival. Methods We prospectively assessed all non-metastatic patients with LGACC treated with IACC at a single institution between 1988 and 2021. For a comparison group, we identified all non-metastatic patients with LGACC treated with excision from the Surveillance, Epidemiology, and End Results (SEER) registry. We calculated disease-specific survival using the Kaplan-Meier and Cox proportional-hazards modeling methods. Results Thirty-five non-metastatic patients with LGACC treated with IACC were identified at a single institution, and 64 patients with non-metastatic LGACC treated with excision were identified in the SEER database. The 5- and 10-year disease-specific survival rates for patients treated with IACC were 84% (95%CI 71-97) and 76% (95%CI 60-92), respectively. While the 5- and 10-year disease-specific survival rates for the population-based cohort were 72% (95%CI 62-82) and 46% (95%CI 32-60). The survival analysis favored IACC, with a 60% lower risk of death (HR: 0.4; 95%CI 0.2-0.9). Conclusion IACC improves disease-specific survival in comparison to a population-based cohort treated with excision. Additional patients treated with IACC at multiple institutions are required to provide further external validity. [ABSTRACT FROM AUTHOR]

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Purpose: The study was undertaken to look into the clinicodemographic profile, management, and clinical outcomes of advanced retinoblastoma at a tertiary care center. Methods: A prospective cohort study was conducted from Jan 2019 to Dec 2022. Forty-two patients of intraocular advanced retinoblastoma were assessed. The treatment protocol was formulated based on size, extension of tumor, and laterality. Primary outcome measure was response to the treatment in terms of regression of tumor and seeds and no evidence of recurrence after 12 month in enucleated eyes. Secondary outcome measures were complications like implant exposure, metastasis, and death associated with each treatment modality. Results: The mean age of the study group was 13 months. The most common presentation was leukocoria with diminished vision. Most of the patients had group E retinoblastoma (n = 40, 95%) as per the International Classification of Retinoblastoma. In 12 patients with group E retinoblastoma, primary enucleation was performed and in six patients, secondary enucleation was done, in which initially, globe salvage treatment was tried. In 30 patients, globe salvage treatment was attempted and we could manage to save 23 eyes. The most common treatment modality was intra-arterial chemotherapy using a triple-drug regimen. One patient developed intracranial spread and died due to systemic metastasis during the follow-up period. Conclusion: The current study showed that globe salvage is possible in advanced retinoblastoma if appropriate therapy is instituted depending upon the extent of the tumor and availability of latest treatment modalities. Intra-arterial chemotherapy using triple drugs can be offered as a first-line therapy in advanced unilateral retinoblastoma as it has been found to be very effective in the present study.

Preoperative intra-arterial chemoradiotherapy (IACRT) can improve the outcome and reduce the extent of surgery in patients with advanced oral cancer. However, the response to this regimen varies among patients, which may be related to the immune status of the tumor. We investigated the effects of proteins involved in tumor immunity on the outcomes of combined IACRT and surgery for oral cancer. We examined CD8 + and FoxP3 + tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression on immune cells and tumor cells in pretreatment biopsy samples from 69 patients diagnosed with oral cancer treated with IACRT at our institution during 2000–2020. Patients with abundant CD8 + TILs had significantly better 5-year disease-specific survival (DSS) compared to that of patients with less infiltration of these cells (P = 0.016). Patients with higher FoxP3 + T-cells invasion had significantly better DSS compared to that of less FoxP3 (P = 0.005). Patients with high PD-L1 expression in tumor cells and immune cells had significantly better DSS than that of patients with low PD-L1 expression in these cells (P = 0.009 and P = 0.025, respectively). Collectively, these results suggest that the tumor immune microenvironment could affect outcomes of IACRT treatment in oral cancer. [ABSTRACT FROM AUTHOR]

PURPOSE: We aimed to analyze our 4-year experience of intra-arterial chemotherapy (IAC) for retinoblastoma (RB) and to examine the tumor response, globe salvage, mortality, and safety profile of IAC in the Malaysian profile. MATERIALS AND METHODS: This was a retrospective, interventional case series. A total of 22 eyes of 20 patients with RB who underwent IAC using melphalan and topotecan from January 2018 to December 2021 in Hospital Kuala Lumpur were retrospectively reviewed. Tumor response, globe salvage, mortality, and safety profile of IAC were compared based on the International Classification of Retinoblastoma. RESULTS: The mean patient age at IAC was 21.3 months. An overall globe salvage rate of 63.6% was observed: more specifically, 100% for Group A, 75% for Groups B and C, 66.7% for Group D, and 42.9% for Group E. Poor tumor response after IAC was significantly associated with a lesser chance of globe salvage (P = 0.045). The overall rate of good tumor response following IAC was 77.3%. Specifically, rates of good tumor response in each group were 100%, 75%, 75%, 83.3% and 71.4% in group A, B, C, D and E, respectively. The mortality rate was 5%. Complications (per-catheterization) included cerebral infarct (2.2%), oxygen desaturation (2.2%), vomiting (26.1%), periorbital edema (8.8%), ptosis (6.5%), fever, femoral hematoma, and hyperpigmentation over lid (4.4% each). CONCLUSION: Four-year experience showed that IAC is a safe and effective method for RB management. Patients with a poor response after IAC may have a lower chance of globe salvage. Careful patient selection is of utmost importance to achieve the best outcome in a setting of limited health-care resources. [ABSTRACT FROM AUTHOR]

Objective: The use of ophthalmic artery chemotherapy (OAC) as a front-line and salvage therapy for retinoblastoma has grown. However, the risk of metastatic death in these patients remains unclear. Materials and Methods: This study of metastatic deaths in OAC may benefit physicians managing retinoblastoma patients. A literature search of Medline, Scopus, Science Direct, and CINAHL was conducted from conception until November 2023. The primary outcome was metastatic death in patients treated with OAC. Results: From the 219 evaluated articles, nine met the inclusion criteria. A total of 596 (635 eyes) patients were treated with OAC; and 20 cases resulted in death due to metastasis of the retinoblastoma. The metastatic mortality rate was 2.5% (95% confidence interval: 0.8%-4.2%) which was statistically significant (p < 0.05). The central nervous system was the most common site of metastasis, followed by multiple sites of metastasis. Conclusion: OAC treatment is associated with the risk of metastatic death, but it is lower than the overall mortality rate of retinoblastoma. Further studies to identify the risk of metastasis are needed.

This retrospective multicenter study examines therapy-induced orbital and ocular MRI findings in retinoblastoma patients following selective intra-arterial chemotherapy (SIAC) and quantifies the impact of SIAC on ocular and optic nerve growth. Patients were selected based on medical chart review, with inclusion criteria requiring the availability of posttreatment MR imaging encompassing T2-weighted and T1-weighted images (pre- and post-intravenous gadolinium administration). Qualitative features and quantitative measurements were independently scored by experienced radiologists, with deep learning segmentation aiding total eye volume assessment. Eyes were categorized into three groups: eyes receiving SIAC (Rb-SIAC), eyes treated with other eye-saving methods (Rb-control), and healthy eyes. The most prevalent adverse effects post-SIAC were inflammatory and vascular features, with therapy-induced contrast enhancement observed in the intraorbital optic nerve segment in 6% of patients. Quantitative analysis revealed significant growth arrest in Rb-SIAC eyes, particularly when treatment commenced ≤ 12 months of age. Optic nerve atrophy was a significant complication in Rb-SIAC eyes. In conclusion, this study highlights the vascular and inflammatory adverse effects observed post-SIAC in retinoblastoma patients and demonstrates a negative impact on eye and optic nerve growth, particularly in children treated ≤ 12 months of age, providing crucial insights for clinical management and future research.

Abstract Background The incidence of multicentric oral cancer is increasing. However, treatment encounters difficulty if each tumor needs to be treated simultaneously. The objective of this clinical case report is to highlight the effect of concurrent chemoradiotherapy with retrograde superselective intra-arterial infusion combined with systemic administration of cetuximab on synchronous multifocal oral squamous cell carcinomas. Case presentation A 70-year-old man presented to the hospital with multiple tumors and oral pain. Three independent tumors were found in the right dorsal tongue, left edge of the tongue, and left lower lip. Based on the characteristic appearance of the lesions and further evaluation, clinical diagnoses of right tongue cancer “T3”, left tongue cancer “T2” and lower left lip cancer “T1”, N2cM0 were made. Treatment was initiated with systemic administration of cetuximab, followed by intra-arterial chemoradiotherapy. Treatment results were complete response on all three local lesions, and left neck dissection was performed following the initial treatment. The patient showed no evidence of recurrence during the 4 years follow-up period. Conclusions This novel combination treatment seems to be a promising strategy for patients with synchronous multifocal oral squamous cell carcinoma.

Intra-arterial chemotherapy (IAC) represents a mainstay in the treatment of retinoblastoma. In a minority of cases, the external carotid artery (ECA) serves as the dominant supply to the central retinal artery and is associated with prolonged fluoroscopy times and higher intraprocedural radiation doses. The aim of this study was to evaluate the utility of time-of-flight (TOF) magnetic resonance angiography (MRA) for prospective determination of internal (ICA) versus ECA dominance for procedural planning. Between April 2017 and December 2020 (44 months), staging MR prior to IAC for retinoblastoma included variant spatial saturation band position TOF angiography. Exams were then retrospectively reviewed for concordance of ICA versus ECA dominance between the two modalities. Eight consecutive patients were included in the study. Mean patient age at time of diagnosis was 20.3 ± 10.7 months (range: 2.7–33.2 months). Ten affected eyes were included (2 cases of bilateral disease), with stage D disease in eight eyes and stage B disease in two eyes. MRA techniques demonstrated antegrade ophthalmic artery (OA) flow in 9/10 (90%) of affected eyes. Subsequent catheter angiography confirmed ICA dominant supply in 9/9 (100%). For a single affected eye (10%), the OA was demonstrated as orthotopic by T2 flow void, nonvisualized on anterior saturation TOF sequences, and faintly visualized on posterior saturation TOF sequences. Aggregate MRA to catheter angiographic concordance was 10/10 (100%). Variant saturation TOF MRA predicts ICA versus ECA dominant supply to the central retinal artery in retinoblastoma.

Purpose: To report a case of recurrent retinoblastoma following transpupillary thermotherapy (TTT) with development of scleral ectasia, as well as their successful treatment with intra-arterial chemotherapy. Observations: A 15-month-old girl with bilateral retinoblastoma presented with recurrent retinoblastoma and associated scleral ectasia with concern for extraocular extension after receiving multiple round of systemic chemotherapy and TTT. Given her negative systemic evaluation, decision was made to pursue intra-arterial chemotherapy. After completion of six rounds of 3-agent intra-arterial chemotherapy, the recurrent retinoblastoma had completely regressed and the scleral ectasia had improved and fibrosed. Conclusions and importance: The sclera is classically viewed as hyperthermy-resistant to TTT. Here, we describe scleral ectasia due to aggressive TTT with recurrence of the retinoblastoma. Our treatment with intra-arterial chemotherapy not only caused complete regression of the recurrent retinoblastoma, but it also contributed to the stabilization and improvement of the weakened scleral.

To describe a patient with retinoblastoma and subsequent maculopathy unrelated to the tumor but related to intra-arterial melphalan documented by pattern electroretinography. Comprehensive ophthalmic evaluation, treatment with intra-arterial chemotherapy and subsequent follow-up including electroretinography to assess for macular dysfunction. A 3-year-old child was evaluated with electrophysiological investigations following treatment of unilateral Group D retinoblastoma with intra-arterial and intravitreal chemotherapy with melphalan. Pattern reversal visual evoked potential amplitude and P100 latency were normal in the left eye, but abnormal and delayed in the right eye. Pattern electroretinograms (pERGs) were abnormal on the right eye. Flash electroretinograms (fERGs) were normal on both eyes. Visual acuity dysfunction of 20/50 attributed to melphalan was seen on the right eye vs 20/40 on the left eye. Our case report demonstrates that pERG rather than fERG should be used to monitor baseline macular function and potential toxicity in children undergoing chemotherapy for retinoblastoma using skin electrodes when corneal electrodes are not tolerated. [ABSTRACT FROM AUTHOR]

Guilherme Castela,1– 3 Joana Providência,1,2 Madalena Monteiro,1 Bárbara Oliveiros,2 Sónia Silva,4 Manuel Brito,4 Egídio Machado,5 Joaquim Neto Murta,1,2 Miguel Castelo-Branco,2,3,&ast; Zélia Correa6,&ast; 1Department of Ophthalmology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; 2Faculty of Medicine, University of Coimbra (FMUC), Coimbra, Portugal; 3Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT), Coimbra, Portugal; 4Department of Pediatric Oncology, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; 5Department of Medical Imaging, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; 6University of Miami, Bascom Palmer Eye Institute, Miami, FL, USA&ast;These authors contributed equally to this workCorrespondence: Guilherme Castela, Department of Ophthalmology, Centro Hospitalar e Universitário de Coimbra, Praceta Prof Mota Pinto, Coimbra, 3004-561, Portugal, Tel +351919702206, Email gcastela@hotmail.comPurpose: We aim to report about effectiveness and safety in the context of our centers’ setting in the management of retinoblastoma with intra-arterial chemotherapy (IAC) in a 5-year retrospective analysis of the Portuguese population.Patients and Methods: Retrospective analysis of consecutive cases of retinoblastoma selected to initiate IAC between 2015 and 2020, at the Portuguese National Reference Center. All included patients underwent complete ophthalmological evaluation under anesthesia with fundus photography. Diagnosis and classification of retinoblastoma was made according to the International Classification of Intraocular Retinoblastoma (ICRB). The patients were further divided into two groups: Group I for primary IAC and Group II for secondary IAC. Tumor recurrence or relapses, systemic metastasis and deaths were documented. Main efficacy outcome included ocular salvage and recurrence-free survival rates estimated using the Kaplan–Meier method.Results: Twenty-eight eyes (19 eyes included in Group I and 9 eyes included in Group II) were eligible and a total of 130 IAC procedures were performed, with a median number of sessions of 4 (range 1– 8) for each treated eye, during a median follow-up of 21 months (range 4– 64). Of the included eyes, 22 (78.6%) were preserved. An overall survival of 100% was achieved. Considering the preserved eyes, the overall median decimal visual acuity achieved at the last visit was 0.15 (range 0.02– 0.8). Three patients had permanent adverse events related to IAC (cataract, vitreous hemorrhage and choroidal ischemia). Considering the survival analysis of recurrence, the mean survival without recurrence was 84.2% for Group I and 66.7% for Group II, and the mean survival without enucleation was 78.6% (no events in Group II).Conclusion: IAC has been shown to be an effective and safe treatment for children with intraocular retinoblastoma. This study demonstrates that IAC is effective even in moderate sample sizes, when a multidisciplinary approach is available.Keywords: retinoblastoma, intra-arterial chemotherapy, ocular oncology, pediatric oncology

PURPOSE: We aimed to analyze our 4-year experience of intra-arterial chemotherapy (IAC) for retinoblastoma (RB) and to examine the tumor response, globe salvage, mortality, and safety profile of IAC in the Malaysian profile. MATERIALS AND METHODS: This was a retrospective, interventional case series. A total of 22 eyes of 20 patients with RB who underwent IAC using melphalan and topotecan from January 2018 to December 2021 in Hospital Kuala Lumpur were retrospectively reviewed. Tumor response, globe salvage, mortality, and safety profile of IAC were compared based on the International Classification of Retinoblastoma. RESULTS: The mean patient age at IAC was 21.3 months. An overall globe salvage rate of 63.6% was observed: more specifically, 100% for Group A, 75% for Groups B and C, 66.7% for Group D, and 42.9% for Group E. Poor tumor response after IAC was significantly associated with a lesser chance of globe salvage (P = 0.045). The overall rate of good tumor response following IAC was 77.3%. Specifically, rates of good tumor response in each group were 100%, 75%, 75%, 83.3% and 71.4% in group A, B, C, D and E, respectively. The mortality rate was 5%. Complications (per-catheterization) included cerebral infarct (2.2%), oxygen desaturation (2.2%), vomiting (26.1%), periorbital edema (8.8%), ptosis (6.5%), fever, femoral hematoma, and hyperpigmentation over lid (4.4% each). CONCLUSION: Four-year experience showed that IAC is a safe and effective method for RB management. Patients with a poor response after IAC may have a lower chance of globe salvage. Careful patient selection is of utmost importance to achieve the best outcome in a setting of limited health-care resources.

Perioperative chemotherapy has been an important part of the comprehensive treatment of advanced gastric cancer. Different from the conventional systemic chemotherapy, preoperative chemotherapy through intra-arterial combined with intra-venous further optimized delivery routes according to characteristics of different drugs on the basis of combination chemotherapy，which has been studied and practiced at our center for more than 20 years. In this review, we will introduce this chemotherapy from the aspects of theoretical basis, development process, treatment advantages, and clinical research. The clinical efficacy and possible treatment mechanisms will be discussed through looking back on both clinic and basic study.

Purpose: To evaluate the efficacy of secondary and salvage intra-arterial chemotherapy (IAC) as a globe salvage treatment modality in advanced and refractory intraocular retinoblastoma. Methods: A retrospective chart review of advanced intraocular retinoblastoma (groups D and E International Classification of Retinoblastoma [ICRB] classification) patients refractory to intravenous chemotherapy (IVC) and undergoing IAC as the secondary and salvage treatment modality between December 2018 and June 2021 was carried out. All patients underwent the IAC procedure by super-selective ophthalmic artery catheterization and with triple-drug chemotherapeutic agents of melphalan, topotecan, and carboplatin. Data were collected about tumor regression, eye salvage, metastasis, and survival outcome at follow-up. Results: Out of 13 patients, 12 patients received secondary IAC after being primarily treated with IVC and focal therapies and one patient received rescue IAC after recurrence following primary IAC. Mean number of IAC cycles administered was 2. Overall, globe salvage rate was 53.84%, with a mean follow-up of 17.53 months (range 6–37 months), three patients had enucleation for residual tumor or tumor recurrence. One patient developed metastasis post enucleation and two patients who were lost to follow-up after enucleation advice for residual tumor developed orbital tumor extension and eventually died of metastasis. Conclusion: Secondary triple-drug IAC following failure of IVC, along with other adjunct treatment modalities might a be a cost-effective option for eye salvage in advanced intraocular retinoblastoma patients who refuse enucleation, with a globe salvage rate of 53.84%. It can also be an effective approach to improve treatment compliance and can help in addressing the barrier of treatment refusal when enucleation is advised.

Intra-arterial chemotherapy (IAC) is the preferred treatment for non-resectable hepatocellular carcinoma. A large fraction of IAC drugs, e.g., Doxorubicin, pass into systemic circulation, causing cardiac toxicity and reducing effectiveness of the procedure. These excessive drugs can be captured by the Chemofilter-a 3D-printable, catheter-based device deployed in a vein downstream of the liver during IAC. In this study, alternative configurations of the Chemofilter device were compared by evaluating their hemodynamic and filtration performance through multiphysics computational fluid dynamics simulations. Two designs were evaluated, a honeycomb-like structure of parallel hexagonal channels (honeycomb Chemofilter) and a cubic lattice of struts (strutted Chemofilter). The computationally optimized Chemofilter design contains three honeycomb stages, each perforated and twisted, which improved Doxorubicin adsorption by 44.6% compared to a straight channel design. The multiphysics simulations predicted an overall 66.8% decrease in concentration with a 2.9 mm-Hg pressure drop across the optimized device compared to a 50% concentration decrease observed during in-vivo experiments conducted with the strutted Chemofilter. The Doxorubicin transport simulations demonstrated the effectiveness of the Chemofilter in removing excessive drugs from circulation while minimizing pressure drop and eliminating flow stagnation regions prone to thrombosis. These results demonstrate the value of the multiphysics modeling approach in device optimization and experimental burden reduction.

Currently there is a lack of effective treatment strategies for malignant superior vena cava syndrome (SVCS). We aim to investigate the therapeutic effect of intra-arterial chemotherapy (IAC) combined with the Single Needle Cone Puncture method for the 125I brachytherapy (SNCP-125I) in treating SVCS caused by stage III/IV Small Cell Lung Cancer (SCLC). Sixty-two patients with SCLC who developed SVCS from January 2014 to October 2020 were investigated in this study. Out of these 62 patients, 32 underwent IAC combined with SNCP-125I (Group A) and 30 patients received IAC treatment only (Group B). Clinical symptom remission, response rate, disease control rate, and overall survival of these two groups of patients were analyzed and compared. The remission rate of symptoms including dyspnea, edema, dysphagia, pectoralgia, and cough of malignant SVCS in Group A was significantly higher than that in Group B (70.5 and 50.53%, P = 0.0004, respectively). The disease control rates (DCR, PR + CR + SD) of Group A and B were 87.5 and 66.7%, respectively (P = 0.049). Response rates (RR, PR + CR) of Group A and Group B were 71.9 and 40% (P = 0.011). The median overall survival (OS) of Group A was significantly longer than that in Group B which was 18 months compared to 11.75 months (P = 0.0360). IAC treatment effectively treated malignant SVCS in advanced SCLC patients. IAC combined with SNCP-125I in the treatment of malignant SVCS caused by SCLC showed improved clinical outcomes including symptom remission and local tumor control rates than IAC treatment only in treating SCLC-induced malignant SVCS. [ABSTRACT FROM AUTHOR]

Background: The incidence of multicentric oral cancer is increasing. However, treatment encounters difficulty if each tumor needs to be treated simultaneously. The objective of this clinical case report is to highlight the effect of concurrent chemoradiotherapy with retrograde superselective intra-arterial infusion combined with systemic administration of cetuximab on synchronous multifocal oral squamous cell carcinomas. Case presentation: A 70-year-old man presented to the hospital with multiple tumors and oral pain. Three independent tumors were found in the right dorsal tongue, left edge of the tongue, and left lower lip. Based on the characteristic appearance of the lesions and further evaluation, clinical diagnoses of right tongue cancer "T3", left tongue cancer "T2" and lower left lip cancer "T1", N2cM0 were made. Treatment was initiated with systemic administration of cetuximab, followed by intra-arterial chemoradiotherapy. Treatment results were complete response on all three local lesions, and left neck dissection was performed following the initial treatment. The patient showed no evidence of recurrence during the 4 years follow-up period. Conclusions: This novel combination treatment seems to be a promising strategy for patients with synchronous multifocal oral squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Intrahepatic cholangiocarcinoma represents 15% of primary liver tumors, second only to hepatocellular carcinoma (HCC). Its incidence in France is increasing. The standard treatment for the localized form is surgical resection followed by adjuvant chemotherapy. In case of liver-limited disease, the use of percutaneous locoregional treatments (thermoablation or external beam radiation therapy) or intra-arterial (in particular selective internal radiation therapy) has been evaluated with promising results as an alternative to surgery in inoperable patients and/or for unresectable tumors. Their use in routine practice can be proposed but with a low level of evidence and precise strategies remain to be defined. [ABSTRACT FROM AUTHOR]

Intra-arterial chemotherapy (IAC) represents a mainstay in the treatment of retinoblastoma. In a minority of cases, the external carotid artery (ECA) serves as the dominant supply to the central retinal artery and is associated with prolonged fluoroscopy times and higher intraprocedural radiation doses. The aim of this study was to evaluate the utility of time-of-flight (TOF) magnetic resonance angiography (MRA) for prospective determination of internal (ICA) versus ECA dominance for procedural planning. Between April 2017 and December 2020 (44 months), staging MR prior to IAC for retinoblastoma included variant spatial saturation band position TOF angiography. Exams were then retrospectively reviewed for concordance of ICA versus ECA dominance between the two modalities. Eight consecutive patients were included in the study. Mean patient age at time of diagnosis was 20.3 ± 10.7 months (range: 2.7–33.2 months). Ten affected eyes were included (2 cases of bilateral disease), with stage D disease in eight eyes and stage B disease in two eyes. MRA techniques demonstrated antegrade ophthalmic artery (OA) flow in 9/10 (90%) of affected eyes. Subsequent catheter angiography confirmed ICA dominant supply in 9/9 (100%). For a single affected eye (10%), the OA was demonstrated as orthotopic by T2 flow void, nonvisualized on anterior saturation TOF sequences, and faintly visualized on posterior saturation TOF sequences. Aggregate MRA to catheter angiographic concordance was 10/10 (100%). Variant saturation TOF MRA predicts ICA versus ECA dominant supply to the central retinal artery in retinoblastoma. [ABSTRACT FROM AUTHOR]

Intra-arterial chemotherapy (IAC) has become the mainstay therapy for retinoblastoma group D and E for the past few decades. However, IAC had never been done in Indonesia before. In this report, we present a case of a 2-year-old girl with recurrent Group D retinoblastoma of the left eye that improved significantly after one session of IAC, the first IAC in Indonesia.

Purpose: To evaluate the efficacy of secondary and salvage intra-arterial chemotherapy (IAC) as a globe salvage treatment modality in advanced and refractory intraocular retinoblastoma. Methods: A retrospective chart review of advanced intraocular retinoblastoma (groups D and E International Classification of Retinoblastoma [ICRB] classification) patients refractory to intravenous chemotherapy (IVC) and undergoing IAC as the secondary and salvage treatment modality between December 2018 and June 2021 was carried out. All patients underwent the IAC procedure by super-selective ophthalmic artery catheterization and with triple-drug chemotherapeutic agents of melphalan, topotecan, and carboplatin. Data were collected about tumor regression, eye salvage, metastasis, and survival outcome at follow-up. Results: Out of 13 patients, 12 patients received secondary IAC after being primarily treated with IVC and focal therapies and one patient received rescue IAC after recurrence following primary IAC. Mean number of IAC cycles administered was 2. Overall, globe salvage rate was 53.84%, with a mean follow-up of 17.53 months (range 6–37 months), three patients had enucleation for residual tumor or tumor recurrence. One patient developed metastasis post enucleation and two patients who were lost to follow-up after enucleation advice for residual tumor developed orbital tumor extension and eventually died of metastasis. Conclusion: Secondary triple-drug IAC following failure of IVC, along with other adjunct treatment modalities might a be a cost-effective option for eye salvage in advanced intraocular retinoblastoma patients who refuse enucleation, with a globe salvage rate of 53.84%. It can also be an effective approach to improve treatment compliance and can help in addressing the barrier of treatment refusal when enucleation is advised. [ABSTRACT FROM AUTHOR]

Background: The prognosis of unresectable gastric cancer is poor, while the efficacy of anti-PD antibodies has not been evaluated. Methods: Patients with unresectable gastric cancer who received intra-arterial chemotherapy (IAC) with sequential anti-PD-1 antibody as induction therapy in Jinling Hospital were retrospectively analyzed. The primary outcome is R0 resection rate. The secondary outcomes include safety, conversion surgery rate, overall survival (OS) and progression free survival (PFS) after postoperative IAC and anti-PD-1 treatments. Meanwhile, Tumor immunity in the microenvironment (TIME) before and after IAC was comprehensively dissected with multiplex immunofluorescence in order to detect possible mechanisms favoring anti-PD-1 treatment response. Results: Between May 2019 and October 2020, 36 patients received at least one cycle of IAC with sequential anti-PD-1 antibody in our institution. The objective response was achieved in 28 patients (77.8%). Thirty patients (83.3%) successfully underwent conversion surgery, among which R0 resection was managed in 25/30 patients, and 23.3% (7/30) was assessed as pathological complete remission. During the median follow-up period of 19.7 months, patients who underwent R0 resection displayed superior OS (HR 0.14 [95% CI 0.04-0.50], P < 0.0001) and PFS (HR 0.11 [0.03-0.44], P < 0.0001) than those who did not. Grade 3 adverse events (AEs) were only encountered in 19.4% patients, no grade 4 AEs observed. In TIME analysis, the number of tertiary lymphoid structures (TLSs) (P = 0.004) were greatly induced by IAC, as well as CD8+ T cells (P = 0.011) and PD-1+ cells (P = 0.025). Meanwhile, Tumor associated macrophages shifted towards anti-tumor M1-like subtypes, with CD68+CD163+ M2-like subpopulation significantly decreased (P = 0.04). Conclusion: Preoperative IAC with sequential anti-PD-1 antibody exhibited promising clinical benefit for unresectable gastric cancer with remarkable conversion rate and R0 resection rate, and also prolonged survival as postoperative regimen. TIME transformation induced by ICA might mediate the additive effect with the immune checkpoint inhibitor. [ABSTRACT FROM AUTHOR]

Purpose The advances in the treatment of retinoblastoma have enabled salvaging the globe in advanced stages with intra-arterial chemotherapy (IAC). We developed a strategy of alternate application of systemic intravenous chemotherapy (IVC) and IAC (referred to as alternate systemic IVC and IAC; ASIAC) to reduce central nervous metastases during IAC and examined its efficacy and safety in eye globe salvage in this study. Materials and Methods Between January 2010 and February 2021, 43 eyes of 40 patients received ASIAC treatment for retinoblastoma at the Yonsei Cancer Center, Yonsei University Health System. Their medical records were reviewed retrospectively to evaluate the eye salvage rate (ESR), defined from diagnosis to enucleation. High-risk retinoblastoma was defined as group D or E by the International Classification of Retinoblastoma. Results The study enrolled 38 and five cases of high-risk and low-risk retinoblastoma, respectively. In total, 178 IAC and 410 IVC courses were administered, with a median of 4 (interquartile range [IQR], 3.0 to 5.0) IAC and 9 (IQR, 6.0 to 11) IVC courses per eye, respectively. The 5-year ESR was 60.4%±8.7% for the whole cohort, 100% for low-risk retinoblastoma, and 53.6%±9.8% for high-risk retinoblastoma. Among those diagnosed since 2015, the 5-year ESR for high-risk retinoblastoma was 63.5%±14.0%. Fifteen eyes underwent enucleation; no viable tumor was found in three enucleated eyes. There were no deaths in this cohort. Conclusion Primary IAC-IVC (i.e., ASIAC) for patients with retinoblastoma was tolerable and effective in salvaging the eye and maintaining survival. [ABSTRACT FROM AUTHOR]

Two-scale CFD modeling is used to design and optimize a novel endovascular filtration device for removing toxins from flowing blood. The Chemofilter is temporarily deployed in the venous side of a tumor during the intra-arterial chemotherapy in order to filter excessive chemotherapy drugs such as Doxorubicin from the blood stream. The device chemically binds selective drugs to its surface thus filtering them from blood, after they have had the effect on the tumor and before they reach the heart and other organs. The Chemofilter consists of a porous membrane made of microscale architected materials and is installed on a structure similar to an embolic protection device. Simulations resolving the microscale structure of the device were carried out to determine the permeability of the microcell membrane. The resulting permeability coefficients were then used for macroscale simulations of the flow through the device modeled as a porous material. The microscale simulations indicate that greater number of microcell layers and smaller microcell size result in increased pressure drop across the membrane, while providing larger surface area for drug binding. In the macroscale simulations, the study of idealized prototypes show that the pressure drop can be reduced by increasing the membrane's tip angle and by decreasing the number of membrane's sectors. Such design, however, can conversely affect the overall drug binding. By decreasing the concentration of toxins in the cardiovascular system, the drug dosage can be increased while side effects are reduced, thus improving the effectiveness of treatment.

PurposeTo investigate the characteristics of the retinal microvasculature of the fellow eyes in patients with unilateral retinoblastoma (RB) after intra-arterial chemotherapy (IAC) through optical coherence tomography angiography.MethodsThis retrospective study enrolled 11 fellow eyes of patients with unilateral RB receiving IAC (group I), nine fellow eyes of patients with unilateral RB receiving IAC and intravenous chemotherapy (IVC) (group II), and 14 age-matched normal eyes (control group). Optical coherence tomography angiography was performed on all individuals. Vascular density of superficial capillary plexus and deep capillary plexus (DCP), foveal avascular zone related parameters, and retinal thickness were measured and compared among the three groups.ResultsThere was no statistical difference in age and logMAR visual acuity among the three groups. Compared with the control group, the vascular density of the DCP was lower in group I and II. Decreased vascular density of FD-300 and thinner thickness of outer plexus layer to Bruch’s membrane were detected in group II compared with the control group. The vascular density and retinal thickness showed no differences between group I and II.ConclusionThe decreased vascular density in the DCP without measurable visual impairment was observed in fellow eyes after IAC or IAC + IVC for unilateral RB. Further studies with a larger sample would be necessary to determine the clinical significance of these findings.

This meta-analysis investigated the efficacies of intra-arterial chemotherapy (IAC) plus intravesical chemotherapy (IVC) versus IVC alone in patients with non–muscle-invasive bladder cancer (NMIBC), and preoperative IAC versus preoperative intravenous chemotherapy (IV) in patients with bladder cancer. We also assessed the adverse reactions (ARs) of IAC. We searched the PubMed, Embase, Cochrane Library, and Web of Science databases for English articles published before April 2021. The qualities of cohort studies and randomized controlled trials were analyzed using the Newcastle–Ottawa Scale and Cochrane risk-of-bias tool, respectively. Effect outcomes were computed by random-effects and fixed-effects models. Statistical analyses were conducted using Stata 16.0 and RevMan v5.3.0. A total of seven articles were included. The analysis revealed that IAC plus IVC significantly prolonged recurrence-free survival (RFS) (hazard ratio [HR] = 0.55, 95% confidence interval [CI] = 0.40–0.76, I2 = 0%) and progression-free survival (PFS) (HR = 0.59, 95% CI = 0.37–0.97, I2 = 0%) compared with IVC alone in NMIBC patients after transurethral resection of bladder tumor (TURBT), but had no effect on overall survival (OS), tumor recurrence interval, or tumor-specific death rate. Preoperative IAC had no significant OS benefit compared with preoperative IV in bladder cancer patients. Regarding ARs, patients treated with IAC were significantly more likely to develop grade 1–2 ARs, including nausea/vomiting (odds ratio [OR] = 26.38, 95% CI = 1.88–370.79, I2 = 78%), neutropenia (OR = 10.15, 95% CI = 3.01–34.24, I2 = 0%), hypoleukemia (OR = 5.49, 95% CI = 1.38–21.82, I2 = 26%), and increased alanine aminotransferase (OR = 12.28, 95% CI = 2.24–67.43, I2 = 0%), but there was no significant difference between grade 1–2 ARs and grade 3–4 ARs in terms of increased creatinine in patients treated with IAC. Therefore, administration of IAC plus IVC after TURBT improved RFS and PFS compared with IAC alone in patients with NMIBC. IAC was associated with mild ARs and was well tolerated by most patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Surgery is the current standard for locally advanced tongue cancer. However, substantial impairment may occur even after treatment. Therefore, more effective and less toxic treatment strategies are needed to avoid a reduction in the patient's quality of life. This study aims to evaluate the efficacy and safety of a novel device that we have developed for retrograde intra-arterial chemotherapy (IACT) in patients with locally advanced tongue cancer. Our study demonstrates that the 3-year overall survival and progression-free survival were 81.6% and 74.2%, respectively. These results are not inferior to those of surgery, and no complications (e.g., cerebral infarction or catheter-related infection) have been associated with IACT were observed. We retrospectively evaluated the safety and effectiveness of an external carotid arterial sheath (ECAS) for intra-arterial chemotherapy (IACT) for locally advanced tongue cancer. Thirty-one patients with the Union for International Cancer Control's 8th TNM stage III–IV tongue cancer underwent IACT using the ECAS combined with RT and systemic chemotherapy with either cisplatin and fluorouracil (FP) or docetaxel, cisplatin, and fluorouracil (TPF) between October 2015 and February 2021. The ECAS was inserted retrogradely via the superficial temporal artery, and the tip was placed in the external carotid artery between the maxillary and facial arteries. A microcatheter was inserted into each tumor-feeding artery through the ECAS under fluoroscopy, wherein cisplatin 50 mg/m2 was administered. IACT was performed weekly with neutralization using sodium thiosulfate. Complete response of the primary lesion was achieved in 28/31 (90%) patients. The median follow-up for all patients was 39 months. The 3-year overall survival, progression-free survival, and local control rates were 81.6%, 74.2%, and 83.4%, respectively. Grade 3 and greater toxicities included oral mucositis (45%), neutropenia (39%), nausea (13%), anemia (10%), thrombocytopenia (10%), dry mouth (10%), and fever (3%). There were no severe complications associated with IACT. In conclusion, the ECAS is feasible and effective for locally advanced tongue cancer. [ABSTRACT FROM AUTHOR]

Purpose: To illustrate the diagnosis and management of an atypical, cyst-like recurrence of retinoblastoma. Observations: A 4-month-old boy was diagnosed with Group B retinoblastoma in the right eye, consisting of a 10 x 9 × 3.6 mm retinal tumor temporal to the macula. He was treated with one session of intra-arterial ophthalmic artery chemotherapy using melphalan, followed by three sessions of diode laser transpupillary thermotherapy (TTT), after which complete tumor regression was achieved. 45 weeks after initial treatment, a cystic lesion was detected adjacent to superior margin of the regressed tumor scar. The differential diagnosis included pigment epithelial detachment, retinal gliosis, secondary retinoschisis, and local tumor recurrence. Multimodal imaging including OCT angiography confirmed the diagnosis of local recurrence manifesting as a vascularized cyst-like lesion. Two additional sessions of TTT achieved sustained tumor regression through 16 months of additional follow-up. Conclusions and Importance: Recurrence of retinoblastoma following chemotherapy typically manifests as enlargement of a previously regressed tumor, or seeding into the vitreous or subretinal space. An unusual cyst-like recurrence of retinoblastoma at the margin of a previously regressed tumor was diagnosed by multimodal imaging. Focal diode laser transpupillary thermotherapy was curative.

BackgroundRetinoblastoma (Rb) is a common ocular malignant tumor in children. Intra-arterial chemotherapy (IAC) has been widely used in children with Rb and has achieved an ideal therapeutic effect. However, IAC has side effects, including anemia and bone marrow suppression, for which explicit evidence on the risk factors is lacking. This study aimed to evaluate the covariates that may affect the occurrence of anemia and bone marrow suppression in children with Rb after IAC.MethodsChildren with Rb admitted between May 2019 and January 2021 were included into the study. The differences in the number of children with anemia and bone marrow suppression before and after IAC according to different covariates were recorded. All potential impact factors were included into the univariate and multivariate regression models to identify the related covariates of post-IAC anemia and bone marrow suppression.ResultsData of 282 children with Rb were retrospectively collected. After IAC, children with Rb had increased severities of anemia (p

Background and PurposeCurrently, there is no optimal dose recommendation for a 120-h continuous infusion of 5-fluorouracil via arterial cannulation for advanced T-stage nasopharyngeal carcinoma (NPC). Thus, the aim of this study was to determine the maximum tolerated dose (MDT), along with the efficacy, late adverse events, and 10-year survival outcome of 5-fluorouracil administered continuously for 120 h combined with cisplatin via the superficial temporal artery in patients with advanced T-stage NPC.Materials and MethodsFifty-one patients with histologically confirmed advanced T-stage NPC were eligible for inclusion in this clinical trial. The patients received induction chemotherapy consisting of cisplatin (20 mg/m2/d for 1–5 d) and 5-fluorouracil, administered continuously for 120 h at different dose gradients via a superficial temporal artery. To identify the MTD of 5-fluorouracil infused arterially, we employed a 3 + 3 design during study phase I. The initial dose administered was 200 mg/m2/d, which then was gradually escalated by 50 mg/m2/d until the MTD was reached. Following two cycles of induction chemotherapy, current radical chemoradiotherapy commenced. We assessed the efficacy, survival, toxicity, and quality of life of patients following treatment.ResultsThe overall response (complete response + partial response) rates following induction chemotherapy in the primary mass and lymph nodes were 100% and 100%, respectively. All 51 (100%) patients achieved T-category down-staging after intra-arterial chemotherapy. The MTD was 450 mg/m2/d for 120 h. No late neurological toxicities, such as brain stem injury, temporal lobe necrosis, and spinal cord injury, were observed. The 5- and 10-year overall survival (OS) rates were 78.0% and 71.7%, respectively, with a median OS of 131 months.ConclusionContinuous infusion of 5-fluorouracil combined with cisplatin via the superficial temporal artery showed promising survival benefits and few toxicities in patients with advanced T-stage NPC.

Purpose: 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. Methods: 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 50 Gy), and bulky nodal lesions were provided an additional 20 Gy. Intra-arterial chemotherapy used a combination of nedaplatin (80 mg/m2) and docetaxel (60 mg/m2). Outcome measures were local control, disease-free survival, overall survival, and adverse events. Statistical analyses were performed using the Kaplan–Meier method. Results: Median follow-up period was 24 months (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 84 mm (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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

The management of retinoblastoma, the most common intraocular malignancy in children, has changed drastically over the last decade. Landmark developments in local drug delivery, namely, safer techniques for intravitreal chemotherapy injection and ophthalmic artery chemosurgery, have resulted in eye globe salvages that were not previously attainable using systemic chemotherapy or external beam irradiation. Novel drugs, oncolytic viruses, and immunotherapy are promising approaches in the treatment of intraocular retinoblastoma. Importantly, emerging studies of the pattern of tumor dissemination and local drug delivery may provide the first steps toward new treatments for metastatic disease. Here, we review recent advances in retinoblastoma treatment, especially with regard to local drug delivery, that have enabled successful conservative management of intraocular retinoblastoma. We also review emerging data from preclinical and clinical studies on innovative approaches that promise to lead to further improvement in outcomes, namely, the mechanisms and potential uses of new and repurposed drugs and non-chemotherapy treatments, and discuss future directions for therapeutic development. [ABSTRACT FROM AUTHOR]

To computationally optimize the design of an endovascular magnetic filtration device that binds iron oxide nanoparticles and to validate simulations with experimental results of prototype devices in physiologic flow testing. Three-dimensional computational models of different endovascular magnetic filter devices assessed magnetic particle capture. We simulated a series of cylindrical neodymium N52 magnets and capture of 1500 iron oxide nanoparticles infused in a simulated 14 mm-diameter vessel. Device parameters varied included: magnetization orientation (across the diameter, "D", along the length, "L", of the filter), magnet outer diameter (3, 4, 5 mm), magnet length (5, 10 mm), and spacing between magnets (1, 3 mm). Top designs were tested in vitro using 89Zr-radiolabeled iron oxide nanoparticles and gamma counting both in continuous and multiple pass flow model. Computationally, "D" magnetized devices had greater capture than "L" magnetized devices. Increasing outer diameter of magnets increased particle capture as follows: "D" designs, 3 mm: 12.8-13.6 %, 4 mm: 16.6-17.6 %, 5 mm: 21.8-24.6 %; "L" designs, 3 mm: 5.6-10 %, 4 mm: 9.4-15.8 %, 5 mm: 14.8-21.2 %. In vitro, while there was significant capture by all device designs, with most capturing 87-93 % within the first two minutes, compared to control non-magnetic devices, there was no significant difference in particle capture with the parameters varied. The computational study predicts that endovascular magnetic filters demonstrate maximum particle capture with "D" magnetization. In vitro flow testing demonstrated no difference in capture with varied parameters. Clinically, "D" magnetized devices would be most practical, sized as large as possible without causing intravascular flow obstruction.

The management of retinoblastoma, the most common intraocular malignancy in children, has changed drastically over the last decade. Landmark developments in local drug delivery, namely, safer techniques for intravitreal chemotherapy injection and ophthalmic artery chemosurgery, have resulted in eye globe salvages that were not previously attainable using systemic chemotherapy or external beam irradiation. Novel drugs, oncolytic viruses, and immunotherapy are promising approaches in the treatment of intraocular retinoblastoma. Importantly, emerging studies of the pattern of tumor dissemination and local drug delivery may provide the first steps toward new treatments for metastatic disease. Here, we review recent advances in retinoblastoma treatment, especially with regard to local drug delivery, that have enabled successful conservative management of intraocular retinoblastoma. We also review emerging data from preclinical and clinical studies on innovative approaches that promise to lead to further improvement in outcomes, namely, the mechanisms and potential uses of new and repurposed drugs and non-chemotherapy treatments, and discuss future directions for therapeutic development.