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Comparison of Retinoblastoma Reduction for Chemotherapy Vs External Beam Radiotherapy

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Comparison of Retinoblastoma Reduction for Chemotherapy Vs External Beam Radiotherapy CLINICAL SCIENCES Comparison of Retinoblastoma Reduction for Chemotherapy vs External Beam Radiotherapy Daniel A. Sussman, MD; Erika Escalona-Benz, MD; Matthew S. Benz, MD; Brandy C. Hayden, BS; William Feuer, MS; Nicole Cicciarelli; Stuart Toledano, MD; Arnold Markoe, MD; Timothy G. Murray, MD Objective: To determine the time course and extent of Results: Twenty-six eyes of 26 patients were evaluated tumor reduction associated with systemic chemo- for tumor response; 18 patients were treated with sys- therapy or external beam radiotherapy (EBRT) in the treat- temic chemotherapy and 8 patients were treated with ment of advanced intraocular retinoblastoma. EBRT. Median follow-up was 36 months. A mean 68% reduction in tumor volume occurred after 1 cycle of che- Methods: Retrospective review of children with Reese- motherapy compared with a 12% reduction at a similar Ellsworth stages IV and V retinoblastoma undergoing pri- time point (1 month) after initiation of EBRT (PϽ.004). mary globe-conserving therapy with either systemic che- There was no statistically significant difference in tu- moreduction or EBRT. Study variables were recorded at mor volume reduction between treatment modalities at baseline, at monthly intervals for the first 6 months, and the 12-month follow-up visit. Both systemic chemore- at 12 months after the initiation of treatment. Tumor vol- duction and EBRT achieved 100% globe conservation and umes were calculated using basal area and height values 100% patient survival in this series. determined by ultrasonography, physical examination, and fundus photographic review. Conclusions: Retinoblastoma reduction exhibits a dif- ferential time course based on the applied primary treat- Main Outcome Measures: Outcome measures in- ment. Systemic chemotherapy is associated with earlier cluded tumor volume, tumor reduction, regression pat- tumor reduction than EBRT. tern, treatment-related complications, metastases, and survival. Arch Ophthalmol. 2003;121:979-984 IMELY DIAGNOSIS and treat- as late as 30 years after primary treat- ment of intraocular retino- ment, but these malignancies may be- blastoma have contributed come less frequent in those patients un- to a marked improvement dergoing EBRT after 12 months of age.12-19 in patient survival.1,2 Re- These potential complications have led Tcently, clinical advances have focused on many clinicians to shift their primary treat- intraocular tumor control enabling in- ment from EBRT toward systemic chemo- creased globe conservation while mini- therapy.4 Systemic chemotherapy has mizing the risk to the child.1-5 In addition proven to be an excellent tool in the treat- to enucleation, available treatments in- ment of retinoblastoma; however, it is not clude cryotherapy, laser ablation, chemo- exempt from complications including my- therapy, scleral plaque radiotherapy, elosuppression leading to neutropenia, From the Bascom Palmer Eye transpupillary thermoablation, external thrombocytopenia, or anemia requiring Institute (Drs Sussman, beam radiotherapy (EBRT), and com- unplanned hospital admissions.6,20-23 The Escalona-Benz, Benz, and bined therapeutic modalities.6,7 External present study compares the rate of regres- Murray, Mss Hayden and beam radiotherapy offers the potential of sion of Reese-Ellsworth stages IV and V Cicciarelli, and Mr Feuer), globe and sight preservation but has sig- retinoblastomas (ie, multiple tumors, some and the Divisions of Pediatric nificant limitations. This treatment mo- larger than 10 disc diameters, and any le- Hematology and Oncology dality has been associated with severe com- sion extending anterior to the ora serrata (Dr Toledano) and Radiation Oncology (Dr Markoe), plications such as cataracts, retinopathy, [stage IV] and massive tumors involving University of Miami School of vasculopathy, facial deformities, and op- more than half the retina [stage Va] and 6,8-11 Medicine, Miami, Fla. The tic neuropathy. In addition, up to 35% vitreous seeding (stage Vb) following pri- authors have no relevant of children with retinoblastoma treated mary therapy with systemic chemo- financial interest in this article. with EBRT develop a second malignancy therapy compared with EBRT. (REPRINTED) ARCH OPHTHALMOL / VOL 121, JULY 2003 WWW.ARCHOPHTHALMOL.COM 979 ©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 Table 1. Patient Demographics* Table 3. Adjunctive Therapy* Those Who Those Who Type of Those Who Those Who Received Received P Adjunctive Received Received Variable Chemotherapy EBRT Total Value Therapy Chemotherapy EBRT Total Age, mean (SD), mo 9 (11) 17 (15) 11 (12) .16 None 0 2 (25) 2 (8) Male 11 (61) 6 (75) 17 (65) .67 Diode laser 9 (50) 1 (13) 10 (39) Race Cryotherapy 0 2 (25) 2 (8) White 9 (50) 6 (75) 15 (58) Diode laser + cryotherapy 9 (50) 3 (38) 12 (46) Black 3 (17) 1 (13) 4 (15) .64 Hispanic 5 (28) 1 (13) 6 (23) Abbreviation: EBRT, external beam radiotherapy. Other 1 (6) 0 1 (4) *Data are given as the number (percentage) of patients. Bilateral disease 14 (78) 7 (88) 21 (81) .99 Positive family history 8 (44) 0 8 (31) .03 All patients in the chemoreduction arm of the study re- R-E stage Vb† 8 (44) 5 (63) 13 (50) .67 ceived carboplatin (20 mg/kg for patients younger than 12 months; 550-600 mg/m2 body surface area for patients older than 12 Abbreviations: EBRT, external beam radiotherapy; R-E, Reese-Ellsworth. months), etoposide phosphate (5 mg/kg if the patient was younger *Data are given as the number (percentage) of patients unless otherwise 2 indicated. than 12 months; 150 mg/m body surface area if the patient was †The R-E stage Vb is vitreous seeding. older than 12 months), and vincristine sulfate (0.05 mg/kg if the patient was younger than 12 months; 1.5-2 mg/m2 body surface area if the patient was older than 12 months). For patients also receiving cyclosporine, cyclosporine was administered as a 5 Table 2. Primary Therapy mg/kg per hour bolus for 2 hours before chemotherapy started, then a 1.5 mg/kg per hour infusion during the next 30 hours if No. (%) the patient weighed less than 12 kg. These doses were ad- Type of Treatment of Patients justed to 4 mg/kg per hour and 1.25 mg/kg per hour, respec- Chemotherapy tively, if the patient weighed between 12 and 30 kg, or 3 mg/kg Carboplatin, etoposide phosphate, 18 (100) per hour and 1 mg/kg per hour, respectively, if the patient and vincristine sulfate weighed more than 30 kg.20 External beam radiotherapy was Cyclosporine 9 (50) administered using the relative lens-sparing technique and in- EBRT dose, rad (Gy) cluded treatment to the 95% isodose line, with a goal dose of 4320 (43.2) 1 (12) 4500 rad (45 Gy) of megavoltage radiation at 180 rad (1.8 Gy) 4500 (45.0) 7 (88) per fraction.5 Abbreviation: EBRT, external beam radiotherapy. CALCULATION OF TUMOR VOLUME METHODS Echographic analysis was performed using an ultrasonic scan- ner (model I3; Innovative Imaging Inc, Sacramento, Calif) or The study protocol was approved by the institutional review the Alcon Ophthoscan-S or the Mini A Systems (Alcon Surgi- board of the University of Miami School of Medicine, Miami, cal, Irvine, Calif). Baseline echographic measurements of all tu- Fla. A retrospective review was performed of medical, photo- mors were obtained while the patient was anesthetized at the graphic, and echographic records of all patients who com- initial examination. Measurement of the maximal tumor height pleted systemic chemotherapy or EBRT as primary treatment was determined from baseline B-scan sections. of retinoblastoma at the Bascom Palmer Eye Institute, Miami, Kowa photographs (Kowa Optimed Inc, Torrance, Calif) with complete documentation from October 1, 1991, to May and/or Retcam 120 images (Massie Research Laboratories Inc, 31, 2001. A total of 175 records was reviewed; 26 patients met Dublin, Calif), obtained at the initial presentation and at each the inclusion criteria of the study. Only patients with Reese- follow-up examination, were used for photographic analysis. Ellsworth stages IV and V retinoblastomas were included in the A digital montage of Kowa images was created using a slide scan- study. Reese-Ellsworth stages I, II, and III retinoblastomas were ner (model LS-2000; Nikon Corp, Tokyo, Japan) and photo- excluded from the study as focal therapies are preferred for pri- graphic montaging software (Sketcher 3.0; Ophthalmic Tech- mary treatment of these tumors at our institution. Patients ini- nologies Inc, Toronto, Ontario). Montage images displayed tially treated outside the Bascom Palmer Eye Institute and pa- borders of tumor and included images of the optic disc for ref- tients undergoing primary enucleation were excluded from the erence. Measurement of the tumor length, width, and basal area study. Those with incomplete or inadequate photographic and/or were determined from photographic analysis using caliper mea- echographic tumor documentation also were excluded from this surements and were internally validated using the optic disc study to allow accurate measurement of the tumor size. If more as a reference (1.5 mm in diameter). Tumor surface areas in than 1 tumor was present, only the largest tumor at baseline Retcam 120 images were obtained using the Retcam software was included in the study. Each patient underwent examina- that enabled us to calculate tumor surface area after outlining tion under anesthesia on presentation and at monthly inter- the margins of the tumor. vals during the follow-up period. Data collected included the Tumor volumes were calculated using radius, basal area, patient’s age at diagnosis, family history, Reese-Ellsworth stage and height values as determined by ultrasonographic, photo- at presentation, type of primary treatment (systemic chemo- graphic, and physical examination. The following formula was therapy or EBRT), number of cycles of treatment, total dose of used for the calculation of the tumor volume radiation, type of adjunctive therapy (laser and/or cryo- 1 2 Volume=( ⁄3ϫ␲ϫheight )ϫ(3ϫradius − height).
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