RETINOBLASTOMA OUTCOMES

[caption id='attachment_4901' align='alignright' width='200'] Francis Munier MD[/caption]

Intravitreal chemotherapy (IViC) and intra-arterial chemotherapy (IAC) represent significant advances in the management of retinoblastoma, reported clinical researchers at the 12th EURETINA Congress. Discussing eye-targeted chemotherapy approaches during a session on ocular tumours, Francis Munier and Carol Shields MD reported their experiences with IViC and IAC. The data show excellent tumour control with improved globe salvage rates and acceptable safety.

“Vitreous seeding represents one of the biggest challenges clinicians face in the management of retinoblastoma, but IViC appears to restore an excellent prognosis for eye preservation in these desperate cases,†said Dr Munier, head, retinoblastoma clinic, Jules-Gonin Eye Hospital, Lausanne, Switzerland. “In our experience, the ocular survival rate using IViC is around 85 per cent, which is totally unprecedented in the field. Now, a prospective, multicentre, Phase II trial, SPOG-RB2011, is under way to validate IViC as a safe and effective salvage option.â€

IViC is being used in eyes with relapsed/ resistant retinoblastoma when the tumour burden is mostly vitreal with or without subretinal seeds, provided that its source is accessible to focal treatment. Careful patient selection and an improved injection technique have been crucial for addressing the risk of tumour spread after IViC, said Dr Munier. Patients are selected for IViC based on imaging assessment with ultrasonic biomicroscopy (UBM). Any of the following findings exclude patients from the procedure: invasion of the anterior and posterior chamber, anterior hyaloid detachment, or the presence of retinal detachment, tumour or vitreous seeds at the needle entry site.

The injection is performed with a very small, 32-gauge needle using an anti-reflux procedure and sterilisation of the needle tract. Dr Munier said he first does an anterior chamber paracentesis, removing a volume of aqueous equal to that of the injection, and sends the specimen for cytopathology to rule out tumour cells in the anterior chamber. “If patients are correctly selected by UBM, there should be no cells in the anterior chamber, and so far all of our samples have been negative,†he said. The needle is inserted perpendicularly, 2.5 to 3.5mm from the limbus at the desired meridian opposite to the seeds and advanced until the needle tip reaches the centre of the vitreous cavity. Dr Munier cautioned that if there is a hyaloid detachment, care must be taken to avoid injecting into the retrohyaloidal space, which would expose the retina to a toxic concentration of the chemotherapeutic agent.

After the drug is delivered and the needle withdrawn, three freeze-thaw cryoapplications are performed at the entry site, and the eye is shaken to distribute the drug. Dr Munier recently published outcomes of IViC in a retrospective interventional case series including 23 eyes. Almost all eyes had prior systemic intravenous and/or intra-arterial chemotherapy. They received a median of four intravitreal injections of melphalan 20-30 mcg given at intervals of seven to 10 days, and all but two eyes received intensive focal therapy to sterilise the seeding source and subretinal seeds. After a median follow-up of 22 months (range nine to 31), the ocular survival rate was 87 per cent, and there were no cases of extraocular tumour recurrence or systemic spread.

“It is noteworthy that no eye required EBR for control of vitreous seeding,†Dr Munier said. He noted that having performed more than 200 IViC injections, he has never observed reflux during the procedure. In the reported series, retinal toxicity was limited to peripheral salt-and-pepper retinopathy at the injection site (10 eyes, 43 per cent), and there were two cases of transient localised vitreous haemorrhage.

[caption id='attachment_4902' align='aligncenter' width='500'] Pictured left to right: The case of a unilateral retinoblastoma group D of the left eye
(diffuse vitreous seeding) (cf photo montage prechemo; macula obscured by the
seeding), successfully treated by 3 cycles of intra-arterial melphalan followed by 3 weekly intravitreal injections of melphalan (cf photo montage 7 months after chemo initiation with healthy macula)[/caption]

Intra-arterial approach

Dr Carol Shields, Oncology Service, Wills Eye Hospital, Philadelphia, US, discussed IAC. In this relatively new method for treating retinoblastoma that requires an interventional neuroradiologist or endovascular neurosurgeon, drug is delivered into the ophthalmic artery under fluoroscopy using a catheter passed after insertion through the femoralartery. IAC is considered in patients with International Classification of Retinoblastoma (ICRB) groups C, D or E retinoblastoma, including use as primary treatment in patients with unilateral disease. It is also used as a secondary treatment for those who fail other methods.

“We are cautious with patient selection for IAC, but we use it every week because it is very powerful,†said Dr Shields, noting that her group has now performed over 200 IAC procedures. Results from a recent report of 17 eyes treated with IAC using melphalan 5.0mg explain Dr Shields’ excitement about the procedure. Complete response was achieved in 14 (88 per cent) eyes, including in nine (82 per cent) of 11 eyes with subretinal seeds and six (67 per cent) of nine eyes with vitreous seeds. Among eyes that were treated with IAC as primary therapy, the success rate was 100 per cent among groups C and D eyes and 33 per cent for group E eyes.

“The addition of topotecan has improved control in eyes with vitreous seeds and in group E,†Dr Shields said. Another report from Dr Shields and colleagues showed high tumour control and globe salvage rates were achieved in eyes with little subretinal fluid and minimal subretinal or vitreous seeds using a minimal exposure technique involving just one or two treatment cycles. Otherwise, an IAC treatment course usually involves three cycles.

They also published their experience using IAC in eyes with retinoblastoma-induced retinal detachment and reported complete reattachment was achieved in all eyes with partial detachment and in almost half of eyes with total detachment. Ocular complications after IAC mostly relate to vascular compromise, that can include small retinal branches or even complete obstruction of the ophthalmic artery in up to five per cent of cases. However, these problems have been minimised over the past two years with improvement in technique, noted Dr Shields.

“On histopathology we occasionally saw chemotherapy precipitates in the arteries that we believe explains the occlusion. Now, however, we are seeing occlusive problems less often using a technique that minimises fluoroscopy time and advances the catheter tip just into the ostium of the ophthalmic artery,†Dr Shields said.