Rachel C Brennan1,2,3, Ibrahim Qaddoumi4,5, Catherine A Billups6, Tracy Kaluzny7, Wayne L Furman4,5, Matthew W Wilson7,8,9. 1. Division of Solid Tumor, Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee. Rachel.brennan@stjude.org. 2. Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee. Rachel.brennan@stjude.org. 3. Department of Ophthalmology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee. Rachel.brennan@stjude.org. 4. Division of Solid Tumor, Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee. 5. Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee. 6. Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee. 7. Department of Surgery, St. Jude Children's Research Hospital, Memphis, Tennessee. 8. Department of Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee. 9. Department of Ophthalmology, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee.
Abstract
BACKGROUND: A total of 5-10% of patients with retinoblastoma (RB) harbor deletion of the long arm (q) chromosome 13 (13q-). The treatment-related toxicities in this population have not been described. METHODS: Sixty-eight RB patients on a single institutional protocol (RET5) from 2005 to 2010 were reviewed. Genetic screening identified 11 patients (seven female) with 13q-. Patients with early (Reese-Ellsworth [R-E] group I-III) disease (6/23 with 13q-) received eight courses of vincristine/carboplatin (VC). Patients with advanced (R-E group IV-V) bilateral disease (2/27 with 13q-) received two courses of vincristine/topotecan (VT) followed by nine courses of alternating VT/VC. Patients undergoing upfront enucleation received histopathology-based chemotherapy: intermediate risk (2/8 with 13q-) or high risk (1/10 with 13q-). Dose reductions were mandated for >7 day delay in two consecutive courses following hematologic toxicity. Grades 3 and 4 hematologic, infectious, and gastrointestinal toxicities were compared between RET5 patients with and without 13q-. RESULTS: Demographics were similar between groups. When present, prolonged neutropenia (median 7 days, range 0-14 days) delayed chemotherapy and resulted in more frequent dose reductions among 13q- patients (5/11) than non-13q- patients (4/57) (P < 0.01). GI toxicity was similar between groups (5/11 13q- vs. 13/57 non-13q-; P = 0.14), but halted chemotherapy in one 13q- patient. Infectious complications and disease outcomes were similar between groups. At follow-up, all patients are alive (median 6.1 years, range 7.6 months-9.5 years). CONCLUSIONS: 13q- RB patients had a higher incidence of neutropenia requiring chemotherapy dose reductions, but did not have increased treatment failure.
BACKGROUND: A total of 5-10% of patients with retinoblastoma (RB) harbor deletion of the long arm (q) chromosome 13 (13q-). The treatment-related toxicities in this population have not been described. METHODS: Sixty-eight RBpatients on a single institutional protocol (RET5) from 2005 to 2010 were reviewed. Genetic screening identified 11 patients (seven female) with 13q-. Patients with early (Reese-Ellsworth [R-E] group I-III) disease (6/23 with 13q-) received eight courses of vincristine/carboplatin (VC). Patients with advanced (R-E group IV-V) bilateral disease (2/27 with 13q-) received two courses of vincristine/topotecan (VT) followed by nine courses of alternating VT/VC. Patients undergoing upfront enucleation received histopathology-based chemotherapy: intermediate risk (2/8 with 13q-) or high risk (1/10 with 13q-). Dose reductions were mandated for >7 day delay in two consecutive courses following hematologic toxicity. Grades 3 and 4 hematologic, infectious, and gastrointestinal toxicities were compared between RET5 patients with and without 13q-. RESULTS: Demographics were similar between groups. When present, prolonged neutropenia (median 7 days, range 0-14 days) delayed chemotherapy and resulted in more frequent dose reductions among 13q-patients (5/11) than non-13q-patients (4/57) (P < 0.01). GI toxicity was similar between groups (5/11 13q- vs. 13/57 non-13q-; P = 0.14), but halted chemotherapy in one 13q-patient. Infectious complications and disease outcomes were similar between groups. At follow-up, all patients are alive (median 6.1 years, range 7.6 months-9.5 years). CONCLUSIONS:13q-RBpatients had a higher incidence of neutropenia requiring chemotherapy dose reductions, but did not have increased treatment failure.
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