NEW YORK (Reuters Health) - For children with group D retinoblastoma, first-line intra-arterial chemo (IAC) may be better than first-line intravenous chemo (IVC), a retrospective study from Switzerland suggests.
First-line IAC is quicker and is associated with better ocular survival and better visual acuity than first-line IVC, Dr. Francis L. Munier of the Gonin Eye Hospital in Lausanne and colleagues report in the British Journal of Ophthalmology, online December 7.
"The evolving treatment of this very rare tumor used to include external beam radiation, which has significant effects on growing faces. Current treatment includes IAC delivered directly to the tumor, eliminating the hair loss, blood count suppression, and immunosuppression seen with systemic chemotherapy," said Dr. J. Allyson Hays, assistant professor of pediatrics at the University of Missouri Kansas City School of Medicine and director of the Histiocytosis Disorder Program at Children's Mercy Kansas City.
"IAC is an established modality for retinoblastoma, although accessibility to the technique is limited for some families," Dr. Hays, who was not involved in the study, told Reuters Health by email.
She added that the new study "is the best comparison we can hope for outside a trial, which would be cumbersome to do and limited by the small number of patients."
Dr. Munier and his colleagues conducted a retrospective review of all consecutive patients with sporadic unilateral group D retinoblastoma treated conservatively between 1997 and 2014 at two academic eye hospitals.
For several years, the primary approach was IVC combined with focal treatments. But from September 2008, IAC replaced IVC as first-line therapy, except in children weighing less than 6 kg.
Patients who had other primary treatments, including IAC or IVC started at different medical centers, patients receiving both IVC and IAC or consultations for second opinion only, and children with bilateral disease were excluded from the study.
The 48 children who met the inclusion criteria received either IAC or IVC as primary treatment. For the 25 patients in the IAC group, the average followup was 41.7 months compared to 105.3 months for the 23 patients in the IVC group.
The treatment duration was much shorter in the IAC group (p<0 .001="" 0.9="" 125-250="" 150="" 1="" 200="" 3.="" 5="" a="" absolute="" after="" an="" and="" at="" both="" carboplatin="" count="" day="" days="" diluted="" etoposide="" every="" given="" glucose="" higher="" hour="" in="" iv="" ivc="" m2="" mg="" ml="" nacl="" nadir="" neutrophil="" of="" on="" one="" or="" over="" p="" the="" three="" thrombocyte="" to="" using="" was="" weeks="" with="">
In children younger than 1 or weighing under 10 kg, the dosage was 5 mg/kg/day for etoposide and 6.7 mg/kg/day for carboplatin. Chemo was started within 24 to 48 hours after the eye exam. Chemo was stopped after a maximum of five doses or as soon as focal treatment alone could be used.
IAC was performed in one day in an outpatient setting under general anesthesia with systemic IV heparinization (25 to 70 IU/kg) through the common femoral artery and the internal carotid artery using a microcatheter mounted on a microguide wire navigated to the ostium of the ophthalmic artery.
A melphalan dose according to weight (range 2.8 to 7.5 mg adjusted to 30 mL) was infused over 30 min (1 mL/min) using the pulsatile injection technique. Chemo was stopped as soon focal tumor treatment alone became possible or chemo continued to a maximum of three doses.
Ten eyes in the IVC group and none in the IAC group were enucleated. The recordable visual acuity of the salvaged eyes was much better in the IAC group (0.9 vs. 1.4 LogMAR, p<0 .01="" complications="" detected="" diseases="" either="" extraocular="" group.="" in="" long-term="" metastases="" no="" or="" p="" systemic="" were="">
"IVC remains a valuable treatment option in bilateral disease for children too young for IAC or, in the rare cases of failure of IAC due to anatomical factors," the authors conclude. "While more evidence is needed, the significant advantages of IAC in terms of local disease control, eye retention, visual function prognosis, time to resolution, reduction in number of relapses and fewer retreatments required indicate that, when available and provided additional risk factors can be reliably identified, IAC is the treatment of choice in group D unilateral disease."
Dr. Alan D. Friedman, professor of oncology and pediatrics at the Johns Hopkins University School of Medicine in Baltimore, Maryland, agreed with the authors that, for young children with unilateral advanced stage retinoblastoma, the study supports the superiority of IAC over IVC.
"IAC offers the advantages of reduced risk of infection and other systemic toxicities, avoidance of central line placement and removal, and potentially reduced risk of secondary malignancy," Dr. Friedman told Reuters Health by email.
But he noted, "The conclusions of this study are tempered by its retrospective nature, its evaluation of a relatively small number of patients (about 24 in each group), differences in local tumor control measures between groups (more use of intravitreal injections in the IAC group), and use of IVC for an average of only 3 cycles when 6 cycles might be considered more standard."
"To the credit of these investigators," added Dr. Friedman, "less than 10% of patients had IAC-induced eye complications leading to marked vision loss, potentially due to their minimizing the number of IAC treatments used."
The corresponding author did not respond to requests for comment.
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