 Thank you everybody for coming to our pediatric grand rounds presentations We're gonna start with dr. Aparna Ramasubramanian and she is going to present a three-year-old with retinoblastoma So we have at presentation a two-year-old who was noted to have a white reflex by the Grand Sardar And this is the white reflex that you see in the left eye on close closer examination of the loco Korea You see it as a nasal loco Korea So on the first examination on the general anesthesia it was a large nasal tumor with a lot of vitreous seeding and Some hemer right here and lot of vitreous heme inferiorly So by the international classification of retinoblastoma this would be a group e tumor and The other I was perfectly normal. There was no family history of retinoblastoma and And this is the ultrasound really large nasal tumor measuring 13 millimeters with a lot of intra tumor Calcification so definitely no doubt that this is a retinoblastoma And this is the fluorescein angiography showing lot of hyperfluorescence in the tumor There was no new escalation of the iris and the intraclopressure was normal So the options at that time where we could of course enucleate the eye we could do systemic chemo though The penetration into the vitreous is not very good. So that was not an option at that time Radiation therapy we do not use it as a primary Primary treatment anymore because these kids are radio sensitive and that and are at a risk for secondary cancers So definitely these two were not options So the main two options available to us that in Inuclation or intra arterial if we go back To our pictures this kid actually has an intact macula. It's all an acyl tumor Though it is a group II and had a lot of vitreous eating We discussed with the family and the plan was to go ahead with the intra arterial chemotherapy No for people who are who have not seen the intra arterial chemotherapy technique It is done by the interventional radiologist We have dr. Fiola at primary children's who's doing it right now So basically what we do is we go through the femoral artery We can only the internal carotid artery and you see here you're right up to this is the ophthalmic artery branch You go up to the ostium of the ophthalmic artery You do a fluoroscopy to confirm that the the arteries perfusing and then you deliver chemo There are a lot of chemo's that are being used for intra arterial Intra arterial chemotherapy primary treatment is with Melphalan and if there is no response There are some people who do topotic and in addition to Melphalan for this kid we did only Melphalan and after we do the chemo we have to do Cerebral angiography to make sure you've not thrown a clot anywhere So this kid actually had three sessions of Melphalan five milligram every month and You know from the systemic standpoint this treatment is really good. These kids don't have to be hospitalized They never require blood transfusion But you have to do weekly CBCs and usually you do see a dip in the in the WBC count and the ANC can come down Almost up to a zero in some cases But I've never had to give transfusion to any of them We just give the regular chemo precautions saying you know stay away from sick people and that kind of stuff So you see here after the first chemo the ANC dip down to zero point nine with subsequent intra arterials Usually the dip is more and the lowest this kid got was zero point six and never got any serious infection or needed antibiotics So that is the nice thing about the intra arterial that it is very concentrated in the eye and the systemic side effects are You know hardly hardly there So this is the tumor response after the three cycles of Intra arterial you see that the main tumor has shown a very nice response But you see the ton of vitreous seeds because some of the mean tumor has also broken off as seeds and This is the ultrasound if we do a before and after you see this was the original tumor and has shown a very nice response The tumor itself has gone from a 13 to a three point five nine So the tumor has shrunk very nicely, but then you have all these vitreous seeds and People who do retinoblastoma will tell you that you know in the story of retinoblastoma the vitreous seeds are the villains They are the hardest to treat. They are just you know, they are just a lot of trouble So the options at this time again we again have we could still enucleate this eye We could do systemic chemo Kimo really does not penetrate into the vitreous. So that's really not an option Radiation. Yes, it does work for vitreous seeds But again only a 50 percentage response for vitreous seeds and then we have the newer treatment Intra vitreal chemotherapy which was a taboo many many years ago saying you never stick a needle in a retinoblastoma Patients eye, but that has changed now and they found that Intra vitreal chemotherapy has a success rate close to 83 percentage, which is higher than radiation therapy So after discussion with the family we decided to go ahead with the intra vitreal chemotherapy because like you said before the skits macula is still intact and Has good potential for version So we went ahead with the intra vitreal chemotherapy before we do the intra vitreal chemotherapy we decide the quadrant that has the least number of vitreous seeds and We always inject through the same quadrant for all the sessions Because the quadrant in which you're injecting you do compromise RP in that region because there'll be a lot of RP modeling in that area, so you always go through the same same quadrant and Before you do it you do a UBM to make sure there is no c-leary body involvement in the region where you're injecting and then You do a vitreous tab the first time you do an anterior chamber vitreous tab to make sure there are no retinoblastoma cells In the anterior chamber. You don't have to do that with subsequent Injections just the first one and if there are no cells seen then like any intra vitreal injection you mark So somewhere between three and a three point five base on the child's age You inject the intra vitreal and as soon as you withdraw the needle you do cryotherapy right at the site Where the needle has gone in and you do a triple-free stall Cryotherapy this is so that even if some cells are trying to come out You are going to freeze them right then and there and after that you kind of juggle the eye so that you let the Medication penetrate all around the vitreous So after five cycles of Melphalan alone We started with a 20 microgram of Melphalan and we slowly escalated it up to a maximum of 25 for this kid There are some there are some people who would go up to 30 micrograms and Dr. Hoffman here would you know tell you about a patient that had severe toxicity with a 30 microgram So I actually never go up to a 30 I just do it between 20 and 25 is kind of like my limit after I've tried 20 for a few times I know that I is able to tolerate it then I might go up to a 25 so with the Melphalan alone the inferior vitreous seeds you see have really nicely responded all these are just calcified seeds But there is a central glob Which really has maybe shrunk a little bit because it's not as fuzzy as the other one But really not a very good response So this time we could have continued giving the Melphalan But I decided to go ahead and add topotican Along with the Melphalan and this kid got three additional cycles of Melphalan with topotican The other thing that I started doing at that point I'm not sure if that helps and it's not been reported is to keep the child in the required position 15 minutes after I do the injection Melphalan is supposed to last up to half an hour in the vitreous cavity So kind of like 15 minutes in this case it was all anterior vitreous So maybe a prone position would help. I don't know if that helps, but I started doing that and We did Melphalan I've stepped down the dosage of Melphalan because it will just be too toxic for the eye so Melphalan 20 and topotican 20 this kid got three cycles and It's hard to appreciate on the photographs, but this is all Non-calcified vitreous seeds whereas these are all calcified except this one is not completely calcified But still these are predominantly this Bulk of vitreous seed here. I would say 90 percentage calcified So there is still that 10 percentage that's not calcified but we kind of reached the eight cycle maximum for this kid and after this I've been watching him for two months now and the seeds haven't changed at all and Sometimes they say that the time you inject to the time you see respond There's sometimes a lag of two to three months. So we're just closely watching this kid. He's very stable He actually has a vision of 2060 because that macular is intact and we are doing patching treatment right now So hopefully he might get a little better or maybe not so So it is a little bothersome to see those seeds But as long as you monitor them very closely and see that they haven't changed some of the seeds never get calcified So so this kid is going to be closely monitored up till age five We did do genetic analysis for the for the kid and he did not have the germline mutation Very narrow I The same kid like that's central glob of seeds I thought in my subsequent follow-up they're getting more calcified So maybe six months down the line, you know, it'll get more calcified than it is now It's hard to say after three cycles of intra arterial, which will be three months Yes, so intra arterial is given monthly So all these kids I usually have them see an oncologist right at the time of diagnosis That's more so that you know, they are aware of this patient in case I need system IKIMO at some point At least we're not starting the whole process again So I usually have them see a oncologist and when I do the intra arterial, you know I usually have them look at the CBC also and I have the you know, primary care Involved in the care also in case, you know, there's an infection or something But I usually don't have them see an oncologist at a regular interval But you know, they are in the loop. They you know So this came from Switzerland, Dr. Francis Nuneer was the first person to start investigating Intravitial for Dr. Blastoma and he did a really large study and you know, if I remember right It was 143 eyes, but somewhere around that range it was somewhere between hundred and hundred and fifty eyes that he studied And he has followed them for like four or five years now and has had no problems with metastasis so I think it is the cryotherapy that you do right at the at the exit of the needle that is beneficial, but I Agree every time I inject, you know, I've done so many now But every time I inject, you know my heart stops because it's always in your mind that never ever inject a retinolus to my eye But it works very well, and we really did not have any options for intravitrials prior to this Sorry for vitreous seeds prior to this so but we still have to find the right medication I do not think Melphalan is the right medication We have to find a better medicine So since they make him out now We are using it predominantly only for bilateral retinoblastomas for unilateral retinoblastomas Most people would go to the intra arterial as the first to round because you really don't need to you know Give chemo to the whole body if you need to get it only to a one eye There are some people who do bilateral inter arterials for bilateral retinoblastoma I do not believe in that at all so for definitely systemic he was a huge role for bilateral retinoblastomas. Thank you