Cycles Of Intra-arterial Chemotherapy Research Articles

INTRA-ARTERIAL CHEMOTHERAPY AS A CLINICAL OPTION FOR METASTATIC COLORECTAL CANCER: CONVERSION OF INOPERABLE LIVER METASTASES TO OPERABLE ILLUSTRATED WITH A CLINICAL CASE.

Colorectal cancer exerts a very high level of liver metastases, even on primary diagnosis, with 80%-90% unresectable nodules. At the same time, the possibility of resection has a significant impact on survival: 5-year survival is 6%-10% without liver surgery and up to 30% upon resection of liver metastases. Finding ways to improve resectability is a topical search for doctors all over the world. One of the promising methods to convert unresectable liver metastases of colorectal cancer into resectable ones is a hepatic artery infusion, or intra-arterial chemotherapy allowing for the delivery of cytotoxic drugs directly to the common hepatic artery via catheter or pump with decreased systemic toxicity and increased local drug concentration. In this article, we discuss the literature data on the impact of intra-arterial chemotherapy on the resectability of colorectal metastases in the liver and present the results of the successful clinical case. The literature shows a positive impact of the hepatic artery infusion on the resectability of hepatic metastases of colorectal cancer. The National Cancer Institute (Ukraine) has its own experience in hepatic artery infusion with further resection of primary-unresectable colorectal metastases in the liver. In our clinical case, a patient with liver-limited metastasis of colorectal cancer was initially inoperable due to the size of tumor lesions and an insufficient residual volume of the liver. Hepatic artery infusion tactics was chosen for this patient. The patient received six cycles of intra-arterial chemotherapy, namely five FOLFOX cycles and one 5-FU cycle, and then met the resectability criteria. Also, it is important to notice that the case demonstrates chemoresistance overcoming, since the patient had disease progression before, following systemically administered XELOX, and the period until readmission of the drugs was less than 6 months. So, hepatic artery infusion can be considered a promising method to convert unresectable liver metastases of colorectal cancer into resectable ones for highly selected patients.

Late metastasis in bilateral familial retinoblastoma and review of literature

A 5-year-old female with bilateral familial retinoblastoma (Group A, Group C) was treated with systemic chemotherapy and three cycles of intra-arterial chemotherapy. She was being followed closely and had no evidence of intraocular recurrence for 4 years. She developed isolated femoral metastasis 5 years after initial diagnosis and was treated with high-dose chemotherapy and stem cell transplant. This case emphasizes the need for metastatic monitoring for low-grade retinoblastoma and points toward delayed tumor latency.

Angiographic characteristics and treatment approach in patients undergoing intra-arterial chemotherapy for retinoblastoma.

To identify the specific clinical and angiographic variables that determine the success of intra-arterial chemotherapy (IAC) in a patient with retinoblastoma. Medical records from patients undergoing intra-arterial chemotherapy for the treatment of retinoblastoma between January 2015 and June 2020 within a large academic ocular oncology practice were retrospectively reviewed. Demographics were recorded together with clinical, ocular, and angiographic variables such as the diameter of the ophthalmic artery (OA), angle of ophthalmic artery takeoff, and branching pattern of ophthalmic vasculature. Forty-four eyes from 33 patients with retinoblastoma treated with IAC were identified. Over the total 32 mean months of follow-up, these patients received 144 total catheterizations and a mean of 3.2 IAC cycles for each eye. The number of IAC cycles and the chemotherapeutic agent used did not vary significantly with worsening International Classification of Retinoblastoma (ICRB) groups (P > 0.1). Cumulative dose did not vary with the ICRB group for eyes treated with melphalan, topotecan, or carboplatin (P > 0.1). A higher ICRB group was associated with a smaller mean ophthalmic artery diameter across all procedures (P = 0.016), and femoral artery diameter did not vary significantly between ICRB groups (P = 0.906). A higher cumulative dose of IAC was significantly associated with a smaller takeoff angle of the OA (melphalan, P = 0.011; topotecan, P = 0.009; carboplatin, P = 0.031) in patients who underwent successful IAC procedures. Ophthalmic artery diameter and femoral artery diameter did not have a significant association (P > 0.1) with higher IAC doses in successful IACs. Cumulative IAC dose was not significantly associated with ophthalmic vasculature branching pattern, presence of choroidal blush, temporary OA vasospasm reported during the procedure, and OA occlusion upon microcatheter placement. In this study, neurosurgical angioanatomy appeared to influence the cumulative dose of chemotherapy needed during IAC for retinoblastoma. In the future, these anatomic variables may be used to guide the frequency of monitoring, dosing, and estimation of recurrence risk.

Single-arm, phase II study of intra-arterial chemotherapy plus total neoadjuvant therapy to optimise complete response in distal rectal cancer: a study protocol

IntroductionOrgan preservation is now considered an acceptable alternative option in distal rectal cancer patients with clinical complete response (cCR) after neoadjuvant chemoradiation (CRT). But the cCR rate is low and...

Efficacy of intra-arterial chemotherapy with sequential anti-PD-1 antibody in unresectable gastric cancer: A retrospective real-world study.

The prognosis of unresectable gastric cancer is poor, while the efficacy of anti-PD antibodies has not been evaluated. 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. 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). 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.

Intra-arterial chemotherapy in refractory and advanced intraocular retinoblastoma.

To evaluate the efficacy of secondary and salvage intra-arterial chemotherapy (IAC) as a globe salvage treatment modality in advanced and refractory intraocular retinoblastoma. 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. 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. 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.

Salvage Intra-arterial Chemotherapy for Recurrent or Persistent Intraocular Retinoblastoma: A Study of 24 Eyes

To analyze the outcomes of salvage intra-arterial chemotherapy (IAC) for recurrent or persistent intraocular retinoblastoma after failure with other treatment modalities. Retrospective study. Twenty-four eyes of 23 patients. Intra-arterial chemotherapy. Globe salvage, metastasis, and death. The mean age at the time of salvage IAC was 41 months (median, 36 months; range, 14-86 months). All patients (n= 23) received IV chemotherapy (IVC) as the primary treatment. The mean number of IVC cycles before salvage IAC was 10 (median, 12; range, 6-18). The indications for salvage IAC were tumor recurrence (n= 17; 71%) or persistent tumor (n= 7; 29%) post-IVC. The mean number of salvage IAC cycles was 3 (median, 3; range, 1-6). Of 24 eyes, 17 eyes (71%) achieved tumor regression with salvage IAC, whereas 7 (29%) eyes displayed poor response. Of these 17 eyes with initial tumor regression, 9 (38%) eyes sustained good response, whereas 8 (33%) eyes displayed tumor recurrence over a mean follow-up period of 21 months (median, 21 months; range, 6-44 months). The mean interval between IAC and tumor recurrence (n= 8) was 4 months (median, 3 months; range, 1-14 months). Of these 8 eyes, globe salvage was achieved in 5 (21%) eyes with additional alternate treatment. Of the 7 eyes with poor response to IAC, globe salvage was achieved in 1 (4%) eye with additional alternate treatment. Overall, globe salvage was achieved in 15 (63%) eyes. Salvage IAC is an effective treatment for recurrent and persistent retinoblastoma, enabling globe salvage in 63% cases. The authors have no proprietary or commercial interest in any materials discussed in this article.

Intra-Arterial Chemotherapy as Primary Treatment for Advanced Unilateral Retinoblastoma in China.

PurposeThis study aimed to evaluate the efficacy and complications of intra-arterial chemotherapy (IAC) as a primary treatment for advanced unilateral retinoblastoma in Chinese patients.MethodsThis study was a retrospective review of patients with advanced unilateral retinoblastoma treated with IAC as the primary treatment. The IAC procedures were performed using a balloon-assisted technique. The clinical status and treatment complications were recorded at each visit. Kaplan–Meier analysis was performed to estimate recurrence-free survival and ocular survival.ResultsIn total, 116 eyes of 116 patients with advanced unilateral retinoblastoma were enrolled, including 66 eyes (57%) in group D and 50 eyes (43%) in group E. All treated eyes received a mean of 3 cycles of IAC (range, 3–5), and 66% of the eyes were combined with local consolidation therapy. The median follow-up time was 39 months (range, 22–57 months). The 3-year recurrence-free survival and ocular survival rates were 68.8% (95% CI, 59.2–76.6%) and 88.5% (95% CI, 80.9–93.2%), respectively. Moreover, the 3-year ocular survival rate in group D was significantly higher than that in group E (96.9%, 76.3%; P < 0.01). The common ocular complication was vitreous hemorrhage (19.8%). No deaths or severe systemic complications occurred.ConclusionPrimary intra-arterial chemotherapy is effective for the treatment of advanced unilateral retinoblastoma, especially in group D, with acceptable toxicity.

The Use of Alternative Routes for the Delivery of Intra-Arterial Chemotherapy for Retinoblastoma

The introduction of intra-arterial chemotherapy (IAC) for treatment of retinoblastoma considerably changed the paradigm by which this disease is managed, with event-free survival rates being above 70%. To analyze efficacy of IAC treatment using alternative approaches to ophthalmic artery catheterization (OAC), such as external carotid artery approach or balloon-assisted drug delivery. This is a retrospective chart review for subjects receiving IAC for retinoblastoma. The primary approach was OAC. In cases in which selective OAC was not feasible, alternative routes including catheterization of the external carotid artery or use of a balloon-assisted drug infusion were used. This study included 197 consecutive patients with 207 retinoblastomas who underwent 658 IAC procedures overall. The mean age at diagnosis was 24mo, and 54.5% of the study population was male. Success rate with IAC was 97% (639). Alternative approaches to OAC were, in total, 42 cases (6.4%)-external carotid artery catheterization and use of ICA balloon were performed in 22 (3.3%) and 20 (3%) cases, respectively. A mean of 3.1 IAC cycles were performed for each patient. In total, there were 23 technical failures of the primary OAC technique (3.4%). Periprocedural adverse events occurred in 4 procedures (0.6%). Use of an alternative technique for chemotherapy delivery other than selective OAC in at least one IAC cycle was not a predictor of enucleation. IAC is a safe and effective treatment option for retinoblastoma. Chemotherapy delivery using alternative techniques is as effective as selective OAC.

Intra-arterial Chemotherapy as Primary Treatment for Cavitary Retinoblastoma: Excellent Response in Eight Tumors

The "cavitary" form of retinoblastoma has historically demonstrated minimal treatment response with intravenous chemoreduction, showing less robust regression and less reduction in tumor size. Intra-arterial chemotherapy (IAC) has been reported to more effectively treat retinoblastoma, allowing many previously unsalvageable eyes to now be saved. The purpose was to report treatment response of cavitary retinoblastoma tumors to IAC. Retrospective case series. Patients presenting with cavitary retinoblastoma who were treated with IAC. Retrospective case series of all patients presenting with cavitary retinoblastoma between August 2014 and January 2019 who were treated with primary IAC. Tumor regression, recurrence, resolution of vitreous and subretinal seeds, number of treatments required, globe salvage, metastasis, and death. Eight cavitary retinoblastoma tumors in 6 eyes of 4 patients were treated with IAC. One hundred percent of the cavitary tumors regressed (8/8 tumors, in 6/6 eyes), and 100% of vitreous and subretinal seeds regressed, with 100% globe salvage. None of the tumors recurred, no patients developed metastases, and no patients died. Eyes were treated with a median of 4.5 cycles of IAC (range, 1-7), with fewer IAC treatments used in the later patients (1-3 treatments per eye for the most recent 3 eyes, compared with 6-7 treatments per eye for the earliest 3 eyes). Mean reduction in thickness was 73.4% (range, 59.7%-84.6%). Mean reduction in basal diameter was 45.5% (range, 24.8%-56.0%). Treatment with IAC results in regression of cavitary retinoblastoma, often with greater reduction in tumor size than has been reported previously with intravenous chemotherapy (IVC). Using up-front triple therapy (e.g., melphalan 0.4 mg/kg, carboplatin 50 mg, and topotecan 2 mg) and noting certain subtle signs of early regression can help to minimize unnecessary additional cycles of treatment.

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

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

Abstract TP55: The Use of Alternative Routes for the Delivery of Intra-Arterial Chemotherapy for Retinoblastoma

Background: The introduction of intra-arterial chemotherapy (IAC) for treatment of retinoblastoma considerably changed the paradigm by which this disease is managed, with event-free survival rates being above 70%. Objective: Our aim is to analyze efficacy of IAC treatment using alternative approaches to OAC such as external carotid artery (ECA) approach or balloon-assisted drug delivery. Methods: This is a retrospective chart review for subjects receiving IAC for retinoblastoma. The primary approach was OAC. In cases where selective OAC was not feasible, alternative routes including catheterization of the ECA or use of a balloon-assisted drug infusion where used. Results: This study included 197 consecutive patients with 207 retinoblastomas who underwent 658 IAC procedures overall. The mean age at diagnosis was 24 months, and 54.5% of the study population was male. Success rate with IAC was 97% (639. Alternative approaches to OAC were in total 42 cases (6.4%) - external carotid artery catheterization and use of ICA balloon were performed in 22 (3.3%) and 20 (3%) cases respectively. A mean of 3.1 IAC cycles were performed for each patient. In total, 23 technical failures of the primary OAC technique (3.4%). Periprocedural adverse events occurred in 4 procedures (0.6%). Use of an alternative technique for chemotherapy delivery other than selective OAC in at least one IAC cycle was not a predictor of enucleation. Conclusions: IAC is a safe and effective treatment option for retinoblastoma. Chemotherapy delivery using alternative techniques is as effective as selective OAC.

Abstract WP20: Intra-Arterial Chemotherapy for Retinoblastoma in Infants&lt;10 kg: 74 Treated Eyes With 222 IAC Sessions

Background: Intra-arterial chemotherapy (IAC) for retinoblastoma (Rb) has dramatically altered the natural history of the disease. The spectacular outcomes associated with a high safety profile have pushed the envelope to offer treatment for patients &lt; 10 kg of weight. Objective: We aim to share our findings and experience in a large series of IAC infusions performed in infants &lt; 10 kg. Methods: A retrospective chart review was performed for patients diagnosed with retinoblastoma and managed with IAC as either primary or secondary treatment. Results: There were 207 Rb tumors of 207 eyes in 197 consecutive patients. Of these, patient weight was 10 kg in 69 (35.7%) and &gt;10 kg in 133 (67.5%) patients. Of the 69 patients weighing &lt; 10 kg, 5 patients had bilateral Rb. Thus, a total of 74 eyes of 69 patients weighing &lt; 10 kg were compared to 133 eyes of 133 patients weighing &gt; 10 kg. Comparison ( &lt; 10 kg vs. &gt;10 kg) revealed the total number of IAC cycles was 222 vs. 436. Periprocedural complications occurred in 2 (0.9%) vs. 2 (0.45%) infusions ( p =0.49). Aborted procedure occurred in 12 (5.4%) vs. 7 (1.6%) infusions ( p =0.005). Enucleation following IAC was required in 14 (18.9) vs. 44 (33%) eyes ( p =0.029). On multivariate analysis, weight &lt; 10 kg was not an independent predictor of complications, procedure failure, or eye enucleation. Conclusions: Our results speak for the safety and efficacy of IAC in patients &lt; 10 kg.

Retinoblastoma vascular perfusion and intra-arterial chemotherapy cycle requirements.

Retinoblastoma is a life- and sight-threatening malignancy. To assess the relationship between tumour perfusion and intra-arterial chemotherapy (IAC) requirements to achieve retinoblastoma control. Retrospective case series at the Ocular Oncology Service of Wills Eye Hospital (Philadelphia, Pennsylvania). Fifty-nine eyes of 55 patients. Review of medical and fluorescein angiography (FA) records for retinoblastoma treated with primary or secondary IAC from 2012 to 2017. Vascular supply of the main tumour was evaluated in the pre-treatment FA. Tumour fluorescence was classified as partial <67% or complete tumour perfusion >67%. Partially vs completely perfused tumours were compared for IAC cycle requirements. There were 59 eyes of 55 patients with pre-treatment FA managed with IAC. Partially perfused tumours (n = 20, 34%) required fewer IAC infusions than completely perfused tumours (n = 39, 66%) (2.5 vs 3.7 infusions, P = .02), even after adjustment for confounding factors (tumour diameter, thickness and drug scheme, adjusted P = .04). Tumour perfusion correlated with number of IAC cycles required for tumour control (r = 0.46, P < .001). For primary IAC (n = 18, 31%), tumour perfusion was not associated with number of IAC cycles (P = .63). For secondary IAC (n = 41, 69%), partially perfused tumours (n = 15, 37%) required fewer IAC infusions than completely perfused tumours (n = 26, 63%) (2.1 vs 3.7 infusions, P < .01). FA demonstrating partial retinoblastoma tumour perfusion is associated with fewer IAC cycle requirements for secondary but not primary IAC. FA might be useful in judging anticipated treatment cycles of retinoblastoma managed with primary or secondary IAC.

Intra-arterial chemotherapy for unilateral advanced intraocular retinoblastoma: Results and short-term complications.

Intra-arterial chemotherapy (IAC) has become an essential technique for the management of advanced intraocular retinoblastoma (RB). In this study, the aim of this article is to describe the clinical results and the short-term complications of IAC performed in our hospital.We retrospectively analyzed patients with newly diagnosed unilateral advanced intraocular (group D or E) RB undergoing IAC from October 2016 to December 2017 in our hospital. We recorded the data including age, gender, cycles of IAC, pathway of arteries approached (ophthalmic artery or middle meningeal artery), ocular and systematic complications, globe salvage.Sixty-one patients underwent IAC performing 189 procedures with a median of 3.1 sessions per eye (range, 1–5 sessions). The overall globe salvage rate is 78.7% (Group D (84.2%), and Group E (69.6%) and followed-up. Short-term ocular complications include eyelid edema (15 cases), ptosis (5 cases), forehead congestion (3 cases), retina hemorrhage (5 cases), choroid atrophy (2 cases), phthisis bulbi (1 case), bradycardia and hypotension during the procedure (7cases), myelosuppressions (6 cases), and nausea and vomiting (5cases).IAC is safe and effective for the treatment of unilateral advanced intraocular RB with a very low complication rate.

Intra-Arterial Chemotherapy as Primary Therapy for Retinoblastoma in Infants Less than 3 Months of Age: A Series of 10 Case-Studies.

PurposeRetinoblastoma is the most common primary malignant intra-ocular tumor in children. Although intra-arterial chemotherapy (IAC) by selectively infusing chemotherapy through the ophthalmic artery has become an essential technique in the treatment of advanced intra-ocular retinoblastoma in children, the outcome of IAC as primary therapy for infants less than 3 months of age remains unknown. In this retrospective study, we reviewed the outcome of IAC as primary therapy for retinoblastoma in infants less than 3 months of age.MethodsWe retrospectively reviewed ten retinoblastoma patients attending our center from January 2009 to September 2015 and beginning primary IAC before the age of 3 months. The patient characteristics, overall outcomes and therapy-related complications were assessed.ResultsThe mean patient age at the first IAC treatment was 10.4 weeks (range 4.9–12.9 weeks). These eyes were classified according to the International Classification of Retinoblastoma (ICRB) as group A (n = 0), B (n = 2), C (n = 0), D (n = 9), or E (n = 2). A total of 28 catheterizations were performed, and the procedure was stopped in one patient because of internal carotid artery spasm. Each eye received a mean of 2.6 cycles of IAC (range 2–4 cycles). After IAC with a mean follow-up of 28.3 months (range 9–65 months), tumor regression was observed in 12 of 13 eyes. One eye was enucleated due to tumor progression. All patients are alive and no patient has developed metastatic disease or other malignancies.ConclusionsOur experience suggests IAC as primary therapy is a feasible and promising treatment for retinoblastoma in infants less than 3 months of age.

HIGHLY SELECTIVE INTRA-ARTERIAL CHEMOTHERAPY FOR THE TREATMENT OF PROGRESSIVE DIFFUSE INTRINSIC PONTINE GLIOMAS (DIPG)

BACKGROUND: DIPG remains a uniformly fatal diagnosis with most children dying of disease between six months and two years from initial diagnosis. Radiation therapy remains the only intervention that alters the natural history of the disease, but is not curative. Given the frequent imaging feature of a non-contrast enhancing mass at diagnosis, the extent of systemic delivery of chemotherapeutics to the pons is uncertain. Attempts have been made to circumvent this issue by various methods including convention-enhanced delivery utilizing catheters inserted into the pons, blood-brain barrier disruption, and intra-arterial (IA) administration of chemotherapy into the vertebral circulation. This pilot study explores the safety, tolerability, and initial efficacy of highly selective intra-arterial administration of melphalan via the basilar artery at the time of clinical progression following initial radiotherapy for DIPG. METHODS: Subjects with a radiologic or biopsy proven diagnosis of DIPG are eligible at the time of symptom and/or radiographic progression in the months following initial irradiation. Consensus of the multidisciplinary Pediatric Neuro-Oncology conference faculty is required. Subjects with a documented hypercoagulable disorder or vasculopathy are not eligible, nor are subjects who have been re-irradiated. Two cycles of IA chemotherapy are planned 4 weeks apart. Under general anesthesia, the vertebral artery (right or left) is catheterized with a 4-French guide catheter. Following a baseline angiogram, a 1.5-French microcatheter is advanced into the mid basilar artery. After angiographic confirmation of positioning, IA delivery of 4 or 6 mg of melphalan is delivered over 30 minutes. Following completion of the procedure, subjects are observed overnight in the Pediatric Intensive Care prior to discharge the following day. Subjects are monitored for toxicity between, and following, IA administrations. RESULTS: To date, 2 children, of a planned cohort of 5 children, have been treated with IA melphalan. Both children tolerated the actual IA administrations without any procedural associated toxicity including the absence of stroke, hemorrhage, or other technical complications. The first child received one of two planned IA administrations but clinically deteriorated shortly before the second IA infusion was planned. The second child received both planned IA administrations and is in early follow-up. CONCLUSIONS: Highly selective IA administration of melphalan to the basilar artery is feasible and acutely tolerated. Updated experience and follow-up with enrolled patients will be presented. SECONDARY CATEGORY: Clinical Neuro-Oncology.

Intra-Arterial Intervention Chemotherapy for Sarcoma and Cancerous Ulcer Via an Implanted Pump

To observe the efficacy of intra-arterial chemotherapy with subcutaneously implanted pump for soft tissue sarcoma in extremities and cancerous ulcer. 31 patients with ulcerative skin squamous cell carcinoma or sarcoma in extremities who received treatment during the period from July 2003 to November 2011 at our hospital were recruited, including 15 male and 16 female patients, aging between 14 and 83 with average age of 49 years old. 10 patients had tumor in upper extremities and 21 patients in lower extremities. The pathological types of studied cases include 9 cases with skin squamous cell carcinoma, 6 cases with synovial sarcoma, 5 cases with malignant fibrous histiocytoma, 3 cases with liposarcoma, 3 cases with osteosarcoma, 2 cases with malignant melanoma, 2 cases with epidermoid sarcoma, and 1 case with protuberans. The main symptoms of cancerous ulcer were pain, infection and hemorrhage; All the studied patients were administrated with cisplatin and doxorubicin by intra-arterial chemotherapy pump, and the patients with squamous cell carcinoma were additionally applied with bleomycin and patients with malignant melanoma were additionally applied with dacarbazine. The chemotherapy efficiency was observed after at 3 cycles of intra-arterial chemotherapy. The total remission rate of pain (RR) was 87 %, and total remission rate of ulcer cicatrization (RR) was 71 %, with ulcer cicatrizing spontaneously in 9 cases and obvious homeostasis in 5 cases with bleeding ulcers. 19 patients underwent surgery after chemotherapy, in which 16 cases had limb-salvage surgery and 3 cases underwent lower leg amputation after chemotherapy, and 3 patients out of 16 cases had local recurrence (19 %). The subcutaneous intra-arterial targeting chemotherapy could be applied to treat refractory sarcoma and cancerous ulcer in extremities to significantly increase the chemotherapeutic concentration at tumor area so as to effectively constrain the tumor rupture induced main symptoms including pain, infection and bleeding, which would help to make a decreased blood supplied and well defined tumor boundary to finally decrease the recurrence rate.

Intra-arterial chemotherapy with doxorubicin and cisplatin is effective for advanced hepatocellular cell carcinoma.

Advanced hepatocellular carcinoma (HCC) remains a fatal disease even in the era of targeted therapies. Intra-arterial chemotherapy (IACT) can provide therapeutic benefits for patients with locally advanced HCC who are not eligible for local therapies or are refractory to targeted therapies. The aim of this retrospective study was to analyze the effect of IACT with cisplatin and doxorubicin on advanced HCC. Methods. Patients with advanced HCC who were not eligible for local therapies or were refractory to sorafenib received doxorubicin (50 mg/m2) and cisplatin (50 mg/m2) infusions into the liver via the transhepatic artery. Between January 2005 and December 2011, a total of 50 patients with advanced HCC received this treatment regimen. The overall response rate (ORR) was 22% in all treated patients. In patients who received at least 2 cycles of IACT, the ORR was 36.7%, and the disease control rate was 70%. Survival rate differed significantly between patients who received only one cycle of IACT (group I) and those who received several cycles (group II). The median progression-free survival was 1.3 months and 5.8 months in groups I and II, respectively (P < 0.0001). The median overall survival was 8.3 months for all patients and was 3.1 months and 12.0 months in groups I and II, respectively (P < 0.0001). The most common toxicity was alopecia. Four patients developed grade 3 or 4 leukopenia. Worsening of liver function, nausea, and vomiting were uncommon side effects. This study demonstrated clinical efficacy and tolerable side effects of repeated IACT with doxorubicin and cisplatin in advanced HCC. Our regimen can be an alternative choice for patients with adequate liver function who do not want to receive continuous infusion of IACT.

MANAGEMENT OF ADVANCED RETINOBLASTOMA WITH INTRAVENOUS CHEMOTHERAPY THEN INTRA-ARTERIAL CHEMOTHERAPY AS ALTERNATIVE TO ENUCLEATION

To determine the efficacy of primary intravenous chemotherapy (IVC) plus secondary intraarterial chemotherapy (IAC) for patients with advanced retinoblastoma. Retrospective, nonrandomized interventional case series of 14 patients with retinoblastoma managed with primary systemic IVC (vincristine, etoposide, and carboplatin for 6 cycles) followed by secondary IAC (melphalan for 1-6 cycles). Fourteen patients with advanced retinoblastoma classified by the International Classification of Retinoblastoma as Group D (n = 6, 43%) or Group E (n = 8, 57%) were treated with IVC as primary treatment and subsequent secondary IAC as rescue or consolidation therapy. The IAC was given for recurrent retinoblastoma and/or subretinal/vitreous seeds in 13 eyes (93%) and for persistent viable retinoblastoma in 1 eye (7%). Enucleation was the alternative option. The mean interval between IVC completion and IAC start was 40 weeks (median, 11 weeks; range, 2-170 weeks) and the mean number of IAC cycles was 3 (median, 3; range, 1-6). After primary IVC plus secondary IAC, globe salvage was achieved in 8 patients (57%) at mean 2-year follow-up. There was no evidence of retinoblastoma metastasis or death and no sign of second cancer or life-threatening complication. For advanced retinoblastoma (Groups D and E) in which enucleation is the alternative option, primary systemic IVC followed by secondary focal IAC provides globe salvage in 57% of the eyes and with no metastatic event.