Patients with choroidal invasion of retinoblastoma can be successfully managed with ophthalmic artery chemosurgery (OAC) and avoid enucleation, according to our research published online first in Ophthalmology Retina.
Worldwide, removing the affected eye has been the standard approach to managing choroidal invasion. Many clinicians have more recently questioned whether choroidal invasion retinoblastoma is truly associated with a higher rate of metastases and whether it warrants enucleation and aggressive treatment with multiagent adjuvant systemic chemotherapy. (1)
We conducted a retrospective review of a small series of four pediatric patients with bilateral retinoblastoma who developed massive choroidal invasion greater than 3 mm in diameter. All four patients responded after one session of OAC at Memorial Sloan Kettering Cancer Center (MSK). After receiving subsequent treatment sessions, all patients successfully retained their affected eye with vision comparable to before treatment and were metastasis-free without systemic chemotherapy at a median follow-up of 28 months. (2)
OAC, pioneered by investigators at MSK over a decade ago (1) is our institutional standard of care for children with retinoblastoma. We were the first center to report in 2018 on successfully using OAC to save the eyes of two patients with choroidal invasion due to retinoblastoma. (3) Our current report provides an update on two previously reported cases and two new cases.
At MSK Kids, we are dedicated to improving outcomes and the quality of life for our young patients. Ninety-five percent of patients with retinoblastoma keep both eyes and maintain normal vision. We have a 99 percent cure rate for retinoblastoma overall.
Treatment Approaches to Choroidal Invasion in Retinoblastoma
Retinoblastoma is the most common eye cancer in children, with about 350 diagnoses annually in the United States. It occurs most often in patients under the age of five. Ninety percent of cases are sporadic, caused by a randomly occurring genetic mutation in chromosome 13. The remaining 10 percent of cases are caused by an inherited genetic mutation. Most patients survive the cancer and go on to lead healthy lives with normal vision. Patients with germline mutations have a higher risk of developing second cancers and a higher mortality risk.
Invasion of the choroid is fairly common in retinoblastoma, with histopathological evidence found in about one-quarter of enucleated eyes. (4) Experts previously thought that eyes with choroidal invasion developed metastatic disease more often and that enucleation was required to improve patient outcomes. Some have recommended enucleation for the purposes of detecting choroidal invasion, and if found, recommending adjuvant systemic chemotherapy. (5)
OAC involves delivering chemotherapy directly to the ocular artery through a catheter inserted through a blood vessel in the patient’s leg while they are under anesthesia. Patients may also undergo further treatment with laser therapy, cryotherapy, radiation, and intraocular injections, as required.
OAC delivers chemotherapy to the eye in concentrations about 100 times that of intravenous delivery, (6), (7) ensuring a high concentration of chemotherapy goes directly to the choroid. Since the systemic dose level is so low, it rarely requires blood product transfusions or causes clinically significant fever or neutropenia. (6)
Study Design
We conducted a retrospective review of a small series of four children with choroidal invasion of retinoblastoma treated with OAC at MSK. Choroidal invasion was diagnosed by amelanotic elevation of the choroid by ophthalmoscopy and confirmed with ultrasonography. (1)
Study Results by Case
Two updated cases
Case 1: A seven-month-old patient was diagnosed with bilateral retinoblastoma, with the right eye classified as Reese Ellsworth (RE)/International Classification of Retinoblastoma/Children’s Oncology Group Version (ICRb) RE Va/ICRb E and the left eye as RE Va/ICRb E. The right eye was enucleated and the left eye was treated with systemic chemotherapy (vincristine, carboplatin, and etoposide (VEC) at another center. After the tumors regrew, the patient was referred to MSK and treated three times with OAC consisting of on treatment of melphalan 2.5 mg and carboplatin 30 mg, and two treatments of melphalan 3 mg and carboplatin 40 mg, followed by laser and two intravitreal injections of melphalan 30 mcg, with control of all tumors. Three months later, the patient developed choroidal invasion. After just one OAC treatment of melphalan 4 mg, carboplatin 40 mg, and topotecan 1 mg, the choroidal invasion completely resolved. The patient had one additional session of OAC consisting of topotecan 2 mg and carboplatin 40 mg. Thirty-five months later, the patient’s vision was 20/60, and no metastases developed. (1)
Case 2: A seven-month infant with familial retinoblastoma was diagnosed with bilateral disease, with both eyes classified as RE IIIa/ICRb C. Twenty-one months following three sessions of OAC (melphalan 3–4 mg and topotecan 0.5 mg) and multiple laser treatments, the patient developed choroidal invasion in the right eye. It disappeared after one OAC treatment of melphalan 5 mg, topotecan 2 mg, and carboplatin 70 mg. The patient received two additional OAC treatments of melphalan 5 mg, topotecan 2 mg, and carboplatin 60 mg. Sixty-six months later, the patient’s vision was 20/200, and no metastases developed. (1)
Two new cases
Case 3: A 23-month-old child was diagnosed with bilateral retinoblastoma, with the right eye classified as RE Vb/ICRb D and the left eye as RE IIa/ICRb D. The left eye was treated with OAC three times (carboplatin 40 mg, topotecan 0.5 mg) in addition to laser, cryotherapy, and three intravitreal melphalan injections (two of 30 mcg and one of 25 mcg). Choroidal invasion developed in the left eye 17 months after this initial treatment. It disappeared entirely within one OAC treatment of melphalan 5 mg, topotecan 1 mg, and carboplatin 40 mg. Two additional OAC treatments were administered with the same drugs and dosages. Eighteen months later, the patient’s vision was Finger Counting, and there was no evidence of metastases. (1)
Case 4: An 11-month-old child was diagnosed with bilateral retinoblastoma, with the right eye classified as RE IIIb/ICRb C and the left eye as RE IVb/ICRb D. She was treated with four cycles of systemic chemotherapy (VEC) at another center. After bilateral recurrences, the child was treated at MSK. She received OAC to both eyes, including carboplatin 30 mg and topotecan 0.5 mg once and melphalan 3 mg and carboplatin 30 mg twice to the right eye. She was also treated with laser, cryotherapy, and intravitreal injections of melphalan 25 mcg seven times and topotecan 20–30 mcg twice. Six months following this treatment, the child developed cilio-choroidal invasion in her right eye. She was treated with OAC consisting of melphalan 5 mg, carboplatin 30 mg, and topotecan 0.5 mg, and the cilio-choroidal invasion disappeared completely within a month. The patient received two additional sessions of OAC (melphalan 5 mg, topotecan 0.5 mg, and carboplatin 30 mg). Twenty months later, there was no cancer recurrence, and the child remained metastases free. Her vision was central, steady, and maintained. (1)
Advancing Outcomes for Children with Retinoblastoma
MSK Kids is the only cancer center in the world with a staff solely dedicated to treating retinoblastoma. Our renowned team of experts continues to pioneer minimally invasive standards of treatment for this illness and work diligently to save lives and sight in our youngest patients.
We are currently conducting a clinical trial investigating the effect of treatment on quality of life in survivors of retinoblastoma in one eye. We hope that information from this study will help improve care for children with this cancer, including follow-up care for survivors.
Read Gigi’s Story to learn more about the first-ever OAC treatment at MSK Kids in 2006.
The study was supported in part by grants from the Fund for Ophthalmic Knowledge, Inc. and an NIH Cancer Center Support Grant (P30 CA008748). All authors declared no relevant financial disclosures or conflicts.