In the current study, we evaluated our initial experience in Egypt to implement OAC for the treatment of both unilateral and bilateral naive retinoblastoma patients. About 34.7% presented with advanced stage and the youngest patient was 2 months old. At such young age, OAC might be challenging. Therefore, only few reports have included this age while applying OAC [14,15,16].
Catheterization was successful in 23 eyes out of 26, with a total of 63 sessions, in the current study. The main reason why the technique failed, in three of our cases, was the sharp angle of the OA which hindered the proper catheterization of its ostium. In such cases, shaping the tip of the guidewire was performed to fit the OA ostium, as described previously [17, 18]. Despite being successful in two eyes of our cases, it failed in the other three eyes. Catheterization, however, was not further forced to avoid OA injury. An alternative approach to overcome the sharp angle of OA was by applying the temporary balloon occlusion technique to the ICA [8, 19]. Yet, we have not apply this maneuver to avoid the risk of thromboembolic complications and to avoid dilution of melphalan over a larger volume of the blood [17, 20]. Another difficulty we encountered here was the reflux of the contrast media back to the ICA. Such reflux usually occurs as a result of a hemodynamic flow imbalance with inversion of the blood flow through multiple collaterals between OA and the MMA [17]. The presence of the catheter inside the OA ostium has been thought to be a trigger factor for this hemodynamic disturbance with activation of the collaterals [17, 21]. Catheterization of the MMA via ECA approach, as previously proposed [17, 19], was successfully performed in such cases.
Initially, tumor control has been achieved in 95.6% of the treated eyes. While 65.2% revealed CR after OAC sessions, 34.8% revealed CR only after additional adjuvant therapy. We relied on melphalan as a single chemotherapeutic drug in treating our patients. It is the primary drug used in OAC and has been shown to be the most powerful one [10, 22]. Other studies have used both single and multiple drug regimen, e.g., carboplatin and topotecan in combination with melphalan [18, 19, 23,24,25,26].Combined drug therapy was particularly employed in more advanced cases [23,24,25] or in tandem therapy [22].
In keeping with our data, Tuncer et al. revealed that, of those who had been treated only with melphalan during OAC, only one eye out of 17 retinoblastomas, with stage D, did not reveal CR [27]. Similarly, other studies achieved high rates of tumor control, even in advanced stages, when relied only on melphalan for OAC [28,29,30]. On the other hand, Thampi et al. achieved good tumor response only in less advanced stages but not in the more advanced retinoblastomas, when used melphalan as a single agent for OAC [31].
In the current study, only one eye (4.3%) developed a recurrence after 19 months. A tumor resistance to the chemotherapy has been recorded previously, particularly, when a single agent is used [27, 32]. Such a resistance might be a reason for the recurrence in our case. Contrast to our results, different studies revealed a higher rate of recurrence. Shield et al. reported a recurrence rate of 19%, after OAC in primary retinoblastomas, including all stages, within 24 months [33]. Furthermore, Tuncer et al, in a 4-year experience, reported a recurrence rate of 29% after OAC in group D retinoblastomas, within the first year [27]. The relatively small sample size, particularly, with the small number of advanced retinoblastomas, in addition to the short follow-up duration, may explain our lower recurrence rate. Our results, however, are in agreement with other studies in which low recurrence rates were recorded after OAC, even in advanced cases [30, 34]. In fact, there were notable variations regarding the disease stage, the number of the eyes received treatment, as well as the follow-up period among the different studies which might, in part, contributed to these results discrepancy. In this context, in 10 years’ experience study conducted by Francis et al. investigating the risk factors associated with recurrence after OAC, they found that in addition to using single chemotherapeutic agent, increase the number of chemotherapeutic agents used in combination, bridge therapy, as well as presence of vitreous seeds at the first visit, older age at the time of presentation, and longer interval between OAC sessions (more than 4 weeks) are all significantly associated with high recurrence rate. The latter was the only factor significantly associated with a high recurrence rate if OAC was accompanied by intravitreal chemotherapy injection. Furthermore, they revealed that eyes which did not develop recurrence in the first year had only 8% risk of recurrence by the 2nd year [32].
In the present study, enucleation was performed due to disease progression in one eye and due to recurrence of the disease in another eye. Eventually, we were able to attain a high globe salvage rate (91.3%). Such results are consistent with other studies [28, 35] in which high globe salvage rates were achieved, and further emphasizing the efficacy OAC in retinoblastoma.
Fortunately, none of our patients developed metastasis and all of them were alive within the stated follow-up period (mean = 18.5 months). In parallel with our data, other studies showed no metastasis developed after OAC [18, 27, 33, 36]. Others reported a low incidence of metastasis [11]. Nevertheless, different studies worldwide revealed that no patient has died from the metastatic disease after OAC [11, 30, 31].
The main ocular complications that we encountered in the current study were ophthalmic artery stenosis and chorioretinal atrophy. The ophthalmic artery narrowing was detected by fluoroscopy, in four eyes, in the late sessions and is likely caused by catheter injury or by the toxic effect of chemotherapy to the vascular endothelium. Localized chorioretinal atrophy was detected in three eyes after either the third or fourth session. It is most likely secondary to the toxic effect of the chemotherapy from earlier sessions, since it takes several months to progress. Previous studies also showed low rates of chorioretinal atrophy [27, 29, 33, 37]. In line with other studies [19, 27], other minor periocular complications such as lid edema and periorbital hyperemia have been reported in our study yet, they were resolved shortly afterward. A transient neutropenia, which is related to the chemotherapy toxicity, has been reported in our series yet, none of our patient required blood transfusion. In addition, reduced tidal volume was evident twice in the current study. Similarly, it has been shown previously in some patients during OAC [38, 39] and has been assumed to evolve secondary to catheter placing in the ICA or OA orifice [40]. In such cases, reduced tidal volume was managed by suspending the catheterization and elevating the airway pressure. Immediate intravenous epinephrine would aid to avoid further hemodynamic collapse [40].
One of our limitations was the lack of availability of other chemotherapeutic drugs during the time of our study. Thus, we relied only on melphalan even in the advanced stages or in tandem therapy. In our future OAC treatments, combined drug therapy will be included. The small sample size is another limitation of this study. Being an initial experience that is less accustomed by clinicians and parents may be the reason behind this.
