SemOpenAlex |

SemOpenAlex

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2071782852> ?p ?o ?g. }

Showing items 1 to 100 of ±154 with 100 items per page.

W2071782852 endingPage "342" @default.
W2071782852 startingPage "335" @default.
W2071782852 abstract "Purpose: To report our experience in superselective ophthalmic artery infusion of melphalan (SOAIM) for intraocular retinoblastoma. Methods: From June 2008 to October 2010, 38 patients (18 women, 20 men; age range at first treatment, 7 months to 22 years) with 41 eyes with retinoblastoma were scheduled for SOAIM, for 17 newly diagnosed retinoblastomas Tumour, Node and Metastasis (TNM) 7th Edition 1a (n = 1), 1b (n = 1), 2a (n = 7), 2b (n = 4) and 3a (n = 4) and 24 retinoblastomas with partial remission/relapse TNM 7th Edition 1b (n = 13), 2a (n = 1) and 2b (n = 10). Eight patients (ten eyes) have been treated by SOAIM alone. Follow-up was 6–27 months in 28 patients (30 eyes). Results: Ophthalmic artery cannulation failed in two patients. Thirty-six patients underwent 140 treatments by internal (n = 112) or external (n = 28) carotid arteries. No major procedural complications occurred. Two patients have been lost to follow-up. Remaining 34 patients (37 eyes) had no metastatic disease. Four patients suffered permanent ocular complications: chorioretinal dystrophy (n = 2), ptosis (n = 1) and strabismus/exotropia (n = 1). Eight (22%) eyes in eight (24%) patients underwent enucleation: 7/16 (43%) newly diagnosed retinoblastomas and 1/22 (4.5%) retinoblastomas undergoing partial remission/relapse. For all treated eyes, Kaplan–Meier eye enucleation-free rates (K-M) were 85.4% (95% CI, 73.3–97.5%), 74.4% (95% CI, 57–91.8%) and still stable at 6, 12 months and 2 years, respectively. For eyes with partial remission/relapse, and eyes at presentation, K–M at 2 years were 95.5% (95% CI, 86.9–100%) and 45.6% (95% CI, 16.6–74.6%), respectively. Conclusion: Superselective ophthalmic artery infusion of melphalan was safe and powerful, especially following other therapies. Superselective ophthalmic artery infusion of melphalan should be added to focal therapies spectrum. In selected cases, melphalan should be combined with other chemotherapeutic agents. Retinoblastoma is the most common primary intraocular malignancy in children worldwide, and generally fatal when left untreated (Abramson et al. 1982; Balmer et al. 2008; Shields & Shields 2010). Modern monitoring and multimodal aggressive treatment including local therapies and systemic chemotherapy result in survival in almost all the patients with intraocular disease. When retinoblastoma escapes local control, enucleation is the standard treatment which allows survival in more than 96% (Abramson & Schefler 2004; Broaddus et al. 2009; MacCarthy et al. 2009; Shields & Shields 2010). Enucleation is also the standard treatment for advanced intraocular retinoblastoma (Reese–Ellsworth stages groups Va and Vb), because it is effective in preventing progression to clinical metastatic disease in 95% (Abramson & Schefler 2004). However, the surgical removal of an eye may be a lifelong disability for parents and child alike (Abramson et al. 2008). This is why, in the last 30 years, ocular oncologists pursue a multimodal treatment strategy of globe preservation, even in eyes with advanced disease and poor visual potential. (Abramson et al. 1982; Kaneko & Suzuki 2003; Shields et al. 2004; Shields & Shields 2008). In the hope of salvaging more of the eyes with retinoblastoma, intraarterial superselective infusion of chemotherapy in the ophthalmic artery has been recently proposed and is extensively discussed in the literature (Abramson et al. 2008; Balmer et al. 2008; Schefler & Abramson 2008; Bracco et al. 2009; Brodie et al. 2009; Shields et al. 2009; Abramson 2010; Abramson et al. 2010a,b; Aziz et al. 2010; Shields & Shields 2010; Gobin et al. 2011). Appropriately trained physicians can safely perform paediatric cerebral angiography (Burger et al. 2006; Raelson et al. 2009; Wolfe et al. 2009), and interventional neuroendovascular procedures practice represents an important and evolving part of the management of paediatric patients (terBrugge 1999; Stiefel et al. 2008; Berenstein et al. 2010). The purpose of this paper is to increase the knowledge about the superselective ophthalmic artery infusion of melphalan in the treatment of retinoblastoma by presenting the preliminary results obtained in our institution. From June 2008 to October 2010, a series of 38 patients (18 women, 20 men; age range at first treatment, 7 months to 22 years) with 41 eyes with retinoblastoma have been scheduled for superselective ophthalmic artery infusion of melphalan. A multidisciplinary group including physicians experienced in ophthalmology and ocular oncology, paediatric oncology, diagnostic neuroradiology, interventional neuroradiology, ocular pathology, genetics and neuroanaesthesiology jointly discussed the opportunity of the treatment and then proposed it to the parents of 37 children and to one adult patient, who gave their informed consent. Twenty patients (22 eyes with retinoblastoma) had been enrolled within an open, not randomised, not controlled study protocol (ART-OFT-RTB-SI-2008) approved by the Ethic Committee of Azienda Ospedaliera Universitaria Senese, Policlinico ‘Santa Maria alle Scotte’, Siena, Italy, and following all the pertinent required guidelines for experimental investigations, including the Tenets of the Declaration of Helsinki. The primary end-point of this study protocol was stable ophthalmoscopic remission at 6 months, including tumour regression patterns type 1, i.e., a completely calcified mass appearing like cottage cheese, type 2, i.e., a mass with fish-flash translucid appearance, type 3, i.e., a partially calcified mass, and type 4, i.e., a flat atrophic scar (Dunphy 1964; Ellsworth 1969; Abramson et al. 1981). The secondary end-points were to avoid enucleation, limit the early and late collateral effects from systemic chemotherapy and preserve visual function. Inclusion criteria were newly diagnosed unilateral or bilateral Reese–Ellsworth groups Va and Vb retinoblastomas, and unilateral or bilateral Reese–Ellsworth groups I to V retinoblastomas with partial remission and/or relapse after focal therapies including cryotherapy, laser ablation, brachytherapy, and external beam radiotherapy, or the association of them, and/or systemic chemotherapy and a patient’s age younger than 5-year-old. Exclusion criteria were diffuse infiltrating retinoblastoma, anterior chamber invasion, secondary glaucoma, vitreous haemorrhage, optic nerve infiltration, extraocular disease extent, and intracranial metastatic disease at gadolinium-enhanced magnetic resonance imaging (MRI) of the head and orbits. Nineteen patients (20 eyes with retinoblastoma) had been scheduled on a compassionate-use basis, before the planning of the above-mentioned study protocol, and during its updating. All of these 19 patients followed the inclusion and exclusion criteria of the approved study protocol, with the exception of patients’ age in six patients (range, 6–22 years), and disease group in one patient with a newly diagnosed unilateral stage group II retinoblastoma with an ophthalmoscopic evidence of malignant transformation from a retinoma (Eagle 2009) which is considered in our experience highly resistant to other treatments (Sampieri et al. 2008, 2009). One patient had been scheduled both in the ART-OFT-SI-2008 protocol and then on a compassionate-use basis, because of the failure of the first procedure. At the time of the schedule for the first intraarterial treatment, the clinical Tumour, Node and Metastasis (TNM) classification according to the 7th edition of cancer was 1a (n = 1), 1b (n = 1), 2a (n = 7), 2b (n = 4) and 3a (n = 4) in 17 newly diagnosed retinoblastomas and 1b (n = 13), 2a (n = 1) and 2b (n = 10) in 24 retinoblastomas with partial remission or relapse. All the procedures have been performed in the angiography room of the Unit NINT Neuroimaging and Neurointervention of our institution, under general anaesthesia. Intravenous heparin was administered to prevent thrombosis because of the presence of catheter systems, initially as a bolus of 75 IU/kg, followed by a continuous infusion of 10–15 IU/kg/hr, to maintain an activated partial thromboplastin time of at least twice the normal time throughout the procedure. The procedures were performed alternatively by the puncture of the right and left femoral arteries where a four-French (F) arterial sheath was placed. A 300 mgI/ml nonionic contrast medium (Iopamidol; Iopamiro, Bracco, Milan, Italy) was used in all the patients. The internal carotid artery ipsilateral to the eye to be treated was then catheterized by a four-F (1.3-mm diameter) guide catheter (Vertebral; Terumo, Tokyo, Japan) and a 0.035-inch hydrophilic polymercoated guide wire (Radiofocus; Terumo) through a display of the vessels by ‘roadmapping’. A lateral arteriogram was then performed to visualize the choroido-retinal enhancement of the eye and cerebral vasculature, to verify whether the prominent flow in the ophthalmic artery was from the internal or the external carotid arteries. Using fluoroscopy and roadmapping, the ophthalmic artery arising from the internal carotid artery was then superselectively catetherized using a flow-directed microcatheter (Magic; Balt Therapeutics, Montgomery, France, or Ultraflow; EV3, Irvine, CA, USA) whose outer diameter at the distal tip was 1.5 F. The external carotid artery and its anastomoses were selectively catheterized by a flow-directed (Magic; Balt Therapeutics) microcatheter whose outer diameter at the distal tip was 1.2 F. The navigation of the microcatheters was facilitated by a 0.08-inch hydrophilic guidewire (Mirage; EV3). The tip of the microcatheter has been manually modified in some cases according to the geometry of the internal carotid artery and ophthalmic arterial ostium, and in all the cases requiring navigation in the external carotid artery. After the stability of the microcatheter tip was ensured, a superselective angiogram was performed to check the patency of the different branches of the ophthalmic artery and to check for choroido-retinal enhancement. Continuous pressurized flushing of both coaxial systems with 0.9% physiologic saline was performed throughout the procedure to reduce friction in the cathether system and to avoid intraarterial clots formation and embolism. In all the patients, melphalan has been used as the only drug for superselective intraarterial infusion. The dose of melphalan was chosen according to the territory infused, that is, the size of the eye at ultrasound and not the body surface area or body weight (Gobin et al. 2001; Abramson et al. 2008, 2010a). When the catheter system was stable and ready for the injection, the drug was prepared in the Pharmacy of our institution as 3–6 mg/ml, and dilated in 30 cm3 of saline, and then carried in the angiographic room. A 30-min superselective infusion was then performed by a pulsatile injection to avoid streaming and inhomogeneous drug delivery (Gobin et al. 2001). A lateral arteriogram was then performed, to rule out procedure-related complications such as vasospasm, embolism or arterial dissection. The catheter system was then withdrawn, the femoral sheath was pulled, and haemostasis of the femoral artery was obtained by manual compression. The patient was then awakened from anaesthesia and kept under observation in the Units of Ophthalmology or Paediatrics. The patient was then discharged after 24 hr of hospitalization without any prescription. The patients were exposed to radiation during fluoroscopic observation and images acquisition. The fluoroscopic observation and image acquisition doses were combined to give the total angiographic dose. Dose–area product (DAP) was then defined as the product of the exposed area or field of view and the radiation dose measured in that area, in Gy × cm2. Standard therapy included a cycle of three treatments at a 3–4-week interval each; however, the joint evaluation of the multidisciplinary group might lead to the decision for further treatments. Ophthalmic evaluations were performed 1–7 days before each treatment and included external examination, visual acuity testing when possible according to patients’ age and collaboration, pupil and motility evaluation, and a complete fundus examination under anaesthesia including Retcam digital photography (Massie Industries, Dublin, CA, USA) and B-scan ultrasound at 12 megahertz (B Scan Plus; Accutome Inc, Malverne, PA, USA). Systemic evaluation included an interval history, weight and height measurements and complete blood counts performed between visits and repeated as clinically indicated. Follow-up head and orbit gadolinium-enhanced MRI has been performed when clinically indicated by the multidisciplinary group. An ophthalmoscopic, clinical, and MRI follow-up of 6–27 months (mean, 13 months) from the last intraarterial treatment is available in 28 patients with 30 eyes with retinoblastoma. Failure of catheterization of the ophthalmic artery occurred in three out of the first ten patients at first treatment, and in three further patients at the first, second, and third treatments, respectively. However, in four of these six patients, the procedure was successfully performed some time later. Thus, 36 patients (Table 1) underwent 140 treatments for 39 eyes with 17 newly diagnosed retinoblastomas and 22 retinoblastomas with partial remission and/or relapse after focal therapies (n = 22) and/or systemic chemotherapy (n = 21). Previous focal therapies included laser ablation (n = 22), cryotherapy (n = 14), brachytherapy (n = 1), external beam radiotherapy (n = 1) and intravitreal melphalan (n = 1). Previous systemic chemotherapy included six cycles of carboplatin and etoposide (n = 21), followed by three or four further cycles of carboplatin, etoposide and vincristine for two eyes. The mean total DAP of the 140 treatments was 8.726 Gy × cm2 (median: 6.72; standard deviation: 11.277) per treatment. Treatments have been performed in one eye with retinoblastoma in 33 patients, in both eyes with retinoblastoma in separate sessions in one patient or in the same session, i.e., the so-called ‘tandem therapy’ (Abramson et al. 2010b) in two patients. Three eyes had only one treatment, 26 eyes completed a treatment cycle, nine eyes two treatment cycles and one eye has undergone the second treatment of the second cycle. The 140 treatments have been performed by the internal (n = 112) or the external (n = 28) carotid arteries. In a third of treatments, at the navigation of the cavernous internal carotid artery or cannulation of ophthalmic artery by the internal carotid artery the patients had increase in airway pressure with reduction of oxygen saturation up to 30%. This has been treated by 100% inspired oxygen concentration. In some cases, bradycardia and hypotension occurred. However, no cardiac arrests neither admissions in the intensive care unit at the end of the procedure occurred. After the treatments, there were no death, stroke or seizures neither dissections, occlusions nor bleeding of the carotid and femoral arteries, as well as occlusion of the central retinal arteries, abnormalities in cornea, anterior chamber or lens. One patient underwent one blood transfusion for the worsening of preexistent chemotherapy-related anaemia. According to the Common Toxicity Criteria/Adverse Events edition 3 (CTCAEV3) (Cancer Therapy Evaluation Program, 2006), haematological adverse events occurred in two patients who suffered grade 1–2 and grade 2 neutropenia. The patient with grade 2 neutropenia had been treated by granulocyte-stimulating colony factor. Ocular/visual adverse events included 37 eyelid dysfunctions (36 grade 2 CTCAEV3, and 1 grade 3 CTCAEV3), i.e., eyelid hyperaemia and oedema (n = 25), ptosis (n = 10), lid oedema and nasal loss of lashes (n = 2), as well as two (1 grade 2 CTCAEV3, and 1 grade 2 CTCAEV3) retinopathies. Another ocular adverse event was strabismus/exotropia in one patient. Dermatology/skin adverse events included 2 grade 1 CTCAEV3 frontal alopecias and 10 grade 1 CTCAEV3 frontal rash. All the local adverse events were transient, with the exception of four patients (all of which with partial remission/relapsed retinoblastomas) who suffered chorioretinal dystrophy with pigment alteration (n = 2), ptosis undergoing surgical correction (n = 1) and the above-mentioned patient with strabismus/exotropia who is improving at 8-month clinical follow-up. Twenty-nine eyes with retinoblastoma in 28 patients have been treated also by cryotherapy and laser ablation during or after the intraarterial cycle(s). Ten eyes with retinoblastoma in eight patients have been treated by superselective ophthalmic artery infusion of melphalan alone. Two treated patients have been lost to follow-up, one after the first treatment and the other one after three treatments. All the other 34 treated patients with 37 eyes with retinoblastoma are alive and free of metastatic disease. Eight out of these 34 patients underwent enucleation of eight out of the 37 treated eyes, because of progression of the disease. Seven were out of the 16 newly diagnosed group Vb retinoblastomas, which have undergone one treatment (n = 1), one cycle of three treatments (n = 3) or two (n = 3) cycles of three treatments. The remaining one was a group Vb retinoblastoma out of 22 with partial remission and/or relapse, which had undergone one intraarterial infusion without satisfactory response. Seven out of these eight eyes had been enucleated in our institution, resulting in a reclassification as pT1 (n = 6), or pT3a (n: 1). Twenty out of the nonenucleated 26 patients with 22 eyes with newly diagnosed (n = 7) or partial regressed and/or relapsed (n = 15) retinoblastomas had a minimum follow-up of 6 months (range: 6–27 months). Type 1 remission has been observed in 19 out of these 22 eyes (Fig. 1). Two eyes showed type 1 remission of the tumour itself followed by focal small peripheral relapses which are being treated by cryotherapy and laser ablation but no radiation therapy. One eye had relapse of the tumour itself after its type 1 remission and then underwent brachytherapy. Newly diagnosed group Vb unilateral retinoblastoma in the left eye of a 3.5-year-old girl treated by selective ophthalmic artery infusion of melphalan. At diagnosis, ophthalmoscopy and ultrasound (A) show a group Vb retinoblastoma. The baby underwent one intraarterial treatment cycle, after which ophthalmoscopy and ultrasound (B) show type I remission. The baby did not undergo further therapies, and 25-month clinical follow-up did not show disease relapse. The remaining six patients with seven eyes with retinoblastoma had a follow-up shorter than 6 months showing types 1 to 3 remission. The Kaplan–Meier eye enucleation-free rates at 6 months were 85.4% (95% confidence interval, 73.3–97.5%), 74.4% at 12 months (95% confidence interval, 57–91.8%) and still stable at 2 years for all the treated eyes. Otherwise, the Kaplan–Meier estimates of eye survival until enucleation at 2 years were 95.5% (95% confidence interval, 86.9–100%) and 45.6% (95% confidence interval, 16.6–74.6%) for eyes with partial remission and/or relapse after focal therapies and/or systemic chemotherapy and at disease presentation, respectively. The first suggestion that intraarterial infusion of chemotherapy may be applicable to intraocular retinoblastoma was introduced more than 50 years ago by a team who proposed direct carotid injection of triethylene melamine (Reese et al. 1958) and followed mainly by Japanese authors who proposed injection of 5-fluorouracil into the frontal or supraorbital artery (Kiribuchi 1966; Kiribuchi & Hasegawa 1968). Melphalan is a powerful alkylating agent whose applications in paediatric oncology have been limited because of its severe bone marrow toxicity with systemic administration. However, melphalan has been demonstrated to be one of the most effective drugs against retinoblastoma (Inomata & Kaneko 1987), and it has been choosen as the agent for carotid injection (Kaneko et al. 1990). A technique has been then developed (Kaneko 1999; Mohri 1993; Suzuki & Kaneko 2004; Yamane et al. 2004) to deliver chemotherapy to the orbit by temporarily occluding the carotid artery distal to the ophthalmic artery and injecting drug in the cervical internal carotid artery. Furthermore, intravitreal injection of melphalan (Ueda et al. 1995) and/or ocular hyperthermia have been associated (Kaneko 1996; Kaneko & Suzuki 2003; Ohshima et al. 2009) to treat vitreous seeding. This technique resulted in common anaesthesia-related adverse events (particularly bradycardia); however, no deaths or strokes were reported. Ophthalmoscopical results were impressive; however, all of the eyes received concomitant treatment, making it difficult to ascertain the contribution of the carotid artery infusion in achieving the excellent clinical outcomes (Suzuki & Kaneko 2004). However, no data on visual results, local complications, electroretinogram testing, pupil testing or ocular side effects have been published. Despite the low rate of complications, in all the reports, the authors pointed out that the infusions were not truly superselective, and intracranial vascular territories also received high concentrations of chemotherapy through the cavernous branches of the internal carotid artery. Additionally, there might be concern that inflation of a nondetachable balloon in the parent artery may lead to increased adverse events, such as it is discussed in the literature about aneurysm coiling in adult patients with cerebral aneurysms (Sluzewski et al. 2006, 2008; Shapiro et al. 2008). In 2008, a team from the Memorial Sloan-Kettering Cancer center and the New York Presbyterian Hospital, New York, USA (Abramson et al. 2008) reported the successful preliminary results of a novel technique of superselective ophthalmic artery infusion of chemotherapy. The treatment was relatively safe and repeatable. The strategy of direct infusion into the ophthalmic artery allows the delivery of high concentrations of chemotherapy to the eye and the tumour, with far lower concentrations to the patient than systemic administration. It has been proposed to define this technique as ‘superselective chemosurgery’, because of the cannulation of a small artery such as the ophthalmic artery, and the overall similarities to surgical procedures by chemotherapy (Abramson et al. 2010a; Gobin et al. 2011). The maximum actual dose per treatment is considered to be 6 mg/ml, because periocular oedema and measurable neutropenia have been encountered at a dose of 7.5 mg (Abramson et al. 2008). However, no complications have been reported after a successful treatment delivering 7.5 mg (Aziz et al. 2010). The treatment may be bilateral into both the eyes during the same session, i.e., the so-called ‘tandem therapy’ (Abramson et al. 2010b), such as in two patients of our series. In tandem therapy, the whole dose should not be higher than 8 mg/ml (Abramson et al. 2010b), to avoid melphalan-related systemic complications. Our 36 treated patients underwent 1, 3 or a maximum of six treatments per eye. We agree that the number of treatments should not exceed six to one eye, at a maximum dose of 6 mg/ml per treatment per eye or 8 mg/ml per treatment in tandem therapy (Abramson et al. 2008, 2010a,b). It has been demonstrated that the retinal function may persist and even recover after superselective ophthalmic artery chemotherapy infusion (Brodie et al. 2009). More recently, the same team reported even more promising clinical results by using a multiagent chemotherapy including also carboplatine, and topotecan, as the initial, primary therapy also for groups II, III and IV retinoblastomas (Abramson et al. 2010a; Gobin et al. 2011). Thus, experienced centres facing retinoblastoma are introducing this treatment in their repertoire, and some other case reports have been published (Shields et al. 2009; Aziz et al. 2010; Shields & Shields 2010). To the best of our knowledge, our single-institution experience is the largest outside the United States. The treatment has been feasible, repeatable and safe. Furthermore, intraarterial melphalan faced also retinoblastoma in older patients. In our experience, the failure of ophthalmic artery cannulation seems to have been consistent with the learning curve of the neurointerventional team and the performance of modern neurointerventional angiographic materials in superselective navigation to reach the ophthalmic artery. Both the precise knowledge of the embryology and anatomical variations of ophthalmic artery including its origin from external carotid artery vessels (Dilenge & Ascherl 1980; Grossman et al. 1982; Jo-Osvatic et al. 1999; Lasjaunias et al. 2001; Hayreh 2006; Perrini et al. 2007; Geibprasert et al. 2009; Gobin et al. 2011) and modern guidewires and microcatheters (Liebman & Severson 2009) allow a safe intraarterial navigation also into the external carotid artery anastomoses, resulting in a larger number of treated eyes (Bracco et al. 2009; Gobin et al. 2011). Notably, in our patients’ population, 28 (22%) out of 140 treatments have been performed by navigation of the external carotid artery. Recently, it has been noted that orbital and ophthalmic vascular alterations may occur with the use of combined systemic chemotherapy and periocular carboplatin, and this might have significant influence on superselective intraarterial chemotherapy (Piña et al. 2010). At the navigation of the cavernous internal carotid artery, or cannulation of the ophthalmic artery by the internal carotid artery, subtle to severe cardiopulmonary effects may occur. This seems consistent with the Japanese experiences during balloon inflated transient occlusion of the internal carotid artery (Mohri 1993; Yamane et al. 2004). A prompt neurointensive care management is required. Properly, intraarterial neuroendovascular treatment-related procedural complications including vasospasm, thromboembolism, dissections, occlusions or even vessel rupture are always possible (Shields & Shields 2010), such as in every intraarterial neuroendovascular procedure. However, the issues of both neurointensive care management and neurointerventional technique are beyond the scope of this paper and will be discussed elsewhere. In our study, we found a Kaplan–Meier eye enucleation-free rates at 2 years of 74.4% (95% confidence interval, 57–91.8%) for all eyes, 95.5% (95% confidence interval, 86.9–100%) for eyes with partial remission and/or relapse after focal therapies and/or systemic chemotherapy and 45.6% (95% confidence interval, 16.6–74.6%) for eyes at disease presentation. These results are not consistent with those by other studies (Abramson et al. 2010a,b; Gobin et al. 2011) that have reported a Kaplan–Meier estimates of ocular event-free (including enucleation and irradiation) survival rates at 2 years of 70.0% (95% confidence interval, 57.9–82.2%) for all eyes, 58.4% (95% confidence interval, 39.5–77.2%) for eyes that had previous treatment failure with intravenous chemotherapy and/or external beam radiation therapy and 81.7% (95% confidence interval, 66.8–96.6%) for eyes that received intraarterial chemotherapy as primary treatment. This discrepancy might be explained by inclusion bias, i.e., a higher relative tumour volume and extent of newly diagnosed retinoblastomas of our patients. Another explanation might be the type and timing of previous focal or systemic therapy. However, we feel that the major difference might be the use of a multiagent chemotherapy including melphalan and other chemotherapeutic agents such as carboplatine and topotecan (Abramson et al. 2010a,b; Gobin et al. 2011). Notably, it seems easy to imagine that a multiagent superselective intraarterial chemotherapy might result in better therapeutical results when compared with a single agent therapy, similarly to what happens for multiagent vs single agent systemic chemotherapy. Melphalan has been demonstrated to be successful also in the treatment of the group II retinoblastoma, such as reported in the literature (Abramson et al. 2010a; Gobin et al. 2011). This might mean that less advanced disease including disease relapses might be faced by the association of superselective ophthalmic artery infusion of melphalan alone. Other chemotherapeutic agents might be associated to melphalan in selected cases with more advanced disease showing multiple risk factors such as diffuse subretinal and/or vitreous seeding or lack of reponse to the first treatment with melphalan alone. Further data regarding tumour response are needed, to assess when to stop even after the first one or two treatments or going on for more treatments or treatment cycles, as well as the need for a multiagent intraocular chemotherapy (Abramson et al. 2010a; Gobin et al. 2011). Similarly, correlation with pathological results and tumour genetics are needed. Local adverse events are generally reversible (Abramson et al. 2010a,b; Marr et al. 2010; Gobin et al. 2011). Permanent adverse ocular events occurred in four of the patients reported herein, including ptosis, strabismus/exotropia and chorioretinal dystrophy with pigment alteration. However, complications may also result from other focal treatments including periocular carboplatin injection (Schmack et al. 2006), diode laser hyperthermia (Gombos et al. 2006), external beam radiotherapy (Abramson et al. 2004; Payne et al. 2009), as well as from systemic multiagent chemotherapy, combined or not with other focal therapies (Gombos et al. 2007; Kim et al. 2008). Finally, a major concern regards the risks resulting from radiation exposure of the children (Mahajan et al. 2009; Vijayakrishnan et al. 2010), as they are at a relatively greater risk for developing radiation-related cancers than adults (Brenner & Elliston 2004; Mills et al. 2006), because of the more rapidly dividing cells in children and the longer life expectancy. However, when an experienced team in paediatric brain catheterization use minimal exposure to the fluoroscopic radiation, the dose to the gonads, abdomen, thorax and brain is generally within safe limits (Burger et al. 2006; Raelson et al. 2009; Wolfe et al. 2009). The effects of even low-dose radiation in retinoblastoma children with germline mutation could be more serious (Roarty et al. 1988; Shields & Shields 2010). The estimated dose following multiple sessions of superselective ophthalmic artery infusion of chemotherapy might result in an accumulation of irradiation toxic effects which could be cataractogenic, or possibly carcinogenic, especially in irradiation-sensitive patients with retinoblastoma (Vijayakrishnan et al. 2010). The effects of even low-dose radiation in retinoblastoma children with germline mutation could be more serious (Roarty et al. 1988; Shields & Shields 2010). Thus, a careful use of fluoroscopy during intraarterial chemotherapy with limited irradiation exposure is required. Our single-institution study has some shortcomings including the relatively small sample size, the very short follow-up, and the association of intraarterial superselective ophthalmic artery infusion of melphalan with other focal therapies. Most notably, our data do not allow to evaluate whether this treatment might be the initial, primary treatment, because we have only ten patients treated by intraarterial melphalan alone. However, many other studies regarding the treatment of retinoblastoma are limited by similar shortcomings. In conclusion, we confirm that the superselective approach to the ophthalmic arteries of patients with retinoblastoma is safe when performed by neuroendovascular interventionists skilled in the angiographic diagnosis and treatment of intracranial vascular diseases. Melphalan superselectively delivered in the ophthalmic artery may allow many globes that are currently being enucleated to be salvaged, despite the low rate of complications from local and systemic toxicity. We observed better results in eyes with partial remission and/or relapse after focal therapies and/or systemic chemotherapy than in eyes at disease presentation. These latter eyes should benefit from the addition of other chemotherapeutic agents to melphalan. We agree that intraarterial superselective ophthalmic artery chemotherapy infusion should be added to the spectrum of local therapies for advanced retinoblastoma, as well as that it might be useful also for less advanced disease. Certainly, only a longer follow-up will allow to know whether this technique is really such powerful, how it has to be associated with other local and systemic treatments, how local or systemic treatments have to be modified, and if any future complications will develop. This work has been supported by the AIGR/ONLUS Associazione Italiana Genitori Retinoblastoma. The authors thank Lucia Monti, MD, Daniele Giuseppe Romano, MD, the Nursing staff, and the Radiological technician staff of the Angiography room of the Unit NINT Neuroimaging and Neurointervention, Department of Neurological and Sensorineural Sciences, as well as the Pharmacy, Azienda Ospedaliera Universitaria Senese, Policlinico ‘Santa Maria alle Scotte’, Siena, Italy. Furthermore, the authors thank Stefania Rossi, Department of Physiopathology, Experimental Medicine, and Public Health, University of Siena, Siena, Italy, for her invaluable help in the statistical analysis. A statement that the study was performed with informed consent and following all the guidelines for experimental investigations required by the Institutional Review Board or Ethics Committee of which all authors are affiliated has been inserted." @default.
W2071782852 created "2016-06-24" @default.
W2071782852 creator A5000553920 @default.
W2071782852 creator A5001966142 @default.
W2071782852 creator A5003514160 @default.
W2071782852 creator A5005698635 @default.
W2071782852 creator A5007467120 @default.
W2071782852 creator A5019727934 @default.
W2071782852 creator A5030794182 @default.
W2071782852 creator A5050073527 @default.
W2071782852 creator A5059267532 @default.
W2071782852 creator A5059768666 @default.
W2071782852 creator A5062665340 @default.
W2071782852 creator A5064306128 @default.
W2071782852 creator A5083316918 @default.
W2071782852 creator A5089858350 @default.
W2071782852 creator A5090380332 @default.
W2071782852 date "2012-01-23" @default.
W2071782852 modified "2023-10-16" @default.
W2071782852 title "Superselective ophthalmic artery infusion of melphalan for intraocular retinoblastoma: preliminary results from 140 treatments" @default.
W2071782852 cites W10347719 @default.
W2071782852 cites W1516698945 @default.
W2071782852 cites W1963960338 @default.
W2071782852 cites W1970615351 @default.
W2071782852 cites W1979271037 @default.
W2071782852 cites W1981561664 @default.
W2071782852 cites W1983322464 @default.
W2071782852 cites W1988278634 @default.
W2071782852 cites W1993927965 @default.
W2071782852 cites W1998482683 @default.
W2071782852 cites W2001324871 @default.
W2071782852 cites W2010408541 @default.
W2071782852 cites W2014003061 @default.
W2071782852 cites W2015903403 @default.
W2071782852 cites W2018748331 @default.
W2071782852 cites W2021369567 @default.
W2071782852 cites W2022478518 @default.
W2071782852 cites W2035483815 @default.
W2071782852 cites W2041560646 @default.
W2071782852 cites W2043068265 @default.
W2071782852 cites W2049004591 @default.
W2071782852 cites W2049929214 @default.
W2071782852 cites W2050617043 @default.
W2071782852 cites W2051928315 @default.
W2071782852 cites W2052058041 @default.
W2071782852 cites W2055347287 @default.
W2071782852 cites W2056183819 @default.
W2071782852 cites W2057230839 @default.
W2071782852 cites W2059933096 @default.
W2071782852 cites W2062696619 @default.
W2071782852 cites W2067611128 @default.
W2071782852 cites W2070445467 @default.
W2071782852 cites W2071214003 @default.
W2071782852 cites W2074511633 @default.
W2071782852 cites W2078578521 @default.
W2071782852 cites W2085681300 @default.
W2071782852 cites W2086386707 @default.
W2071782852 cites W2088201561 @default.
W2071782852 cites W2095191852 @default.
W2071782852 cites W2096414062 @default.
W2071782852 cites W2103846152 @default.
W2071782852 cites W2123412585 @default.
W2071782852 cites W2136670281 @default.
W2071782852 cites W2138470725 @default.
W2071782852 cites W2142480746 @default.
W2071782852 cites W2151681304 @default.
W2071782852 cites W2153549888 @default.
W2071782852 cites W2165600074 @default.
W2071782852 cites W2167249670 @default.
W2071782852 cites W2169878140 @default.
W2071782852 cites W4322702673 @default.
W2071782852 cites W564629909 @default.
W2071782852 cites W1981192968 @default.
W2071782852 doi "https://doi.org/10.1111/j.1755-3768.2011.02296.x" @default.
W2071782852 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22268993" @default.
W2071782852 hasPublicationYear "2012" @default.
W2071782852 type Work @default.
W2071782852 sameAs 2071782852 @default.
W2071782852 citedByCount "51" @default.
W2071782852 countsByYear W20717828522012 @default.
W2071782852 countsByYear W20717828522013 @default.
W2071782852 countsByYear W20717828522014 @default.
W2071782852 countsByYear W20717828522015 @default.
W2071782852 countsByYear W20717828522016 @default.
W2071782852 countsByYear W20717828522017 @default.
W2071782852 countsByYear W20717828522018 @default.
W2071782852 countsByYear W20717828522019 @default.
W2071782852 countsByYear W20717828522020 @default.
W2071782852 countsByYear W20717828522021 @default.
W2071782852 countsByYear W20717828522022 @default.
W2071782852 countsByYear W20717828522023 @default.
W2071782852 crossrefType "journal-article" @default.
W2071782852 hasAuthorship W2071782852A5000553920 @default.
W2071782852 hasAuthorship W2071782852A5001966142 @default.
W2071782852 hasAuthorship W2071782852A5003514160 @default.
W2071782852 hasAuthorship W2071782852A5005698635 @default.
W2071782852 hasAuthorship W2071782852A5007467120 @default.
W2071782852 hasAuthorship W2071782852A5019727934 @default.