CLINICAL
AND
LABORATORY OBSERVATIONS
Very Late Relapse of Bilateral Retinoblastoma Jung Yoon Choi, MD,*w Hyoung Jin Kang, MD, PhD,*w Ji Won Lee, MD, PhD,*w Hee Young Ju, MD,*w Che Ry Hong, MD,*w Hyery Kim, MD, PhD,wz Young Suk Yu, MD, PhD,y Sung-Hye Park, MD, PhD,8 Jung-Eun Cheon, MD, PhD,z Kyung Duk Park, MD, PhD,*w and Hee Young Shin, MD, PhD*w
Summary: Retinoblastoma usually recurs within the first few years after treatment completion. We report a rare case of very late relapse in a 6-month-old girl who was diagnosed with bilateral retinoblastoma. The patient achieved first remission after treatment with neoadjuvant chemotherapy, enucleation of the right eye, local laser therapy of the left eye, and adjuvant chemotherapy. Extraocular relapse with multiple metastases occurred 13 years and 8 months after treatment. The patient is currently in second complete remission after receiving high-dose chemotherapy and autologous stem cell transplantation. In conclusion, long-term follow-up is needed for early detection of recurrent retinoblastoma. Key Words: retinoblastoma, recurrence, enucleation
(J Pediatr Hematol Oncol 2015;37:e264–e267)
R
etinoblastoma is the most common intraocular malignancy in childhood. Most retinoblastoma patients are diagnosed before 3 years of age. Bilateral retinoblastoma comprises 20% to 30% of all retinoblastoma cases, and usually presents at a younger age than unilateral disease.1
Because most patients with retinoblastoma are young, close observation for long-term complications including relapse is important for improving survival and quality of life. There are few reports of long-term follow-up >10 years after completion of treatment.2–4 We describe a case of bilateral retinoblastoma in a 6-month-old female who experienced a very late relapse at 13 years and 8 months posttherapy.
ETHICS STATEMENT This study was approved by the institutional review boards of the Seoul National University Hospital, Seoul, Korea (IRB number: 1408-032-600). Informed consent was waived by the board.
CASE REPORT A 6-month-old female was referred to our institution for leukocoria and divergent strabismus in both eyes. Computed tomography and fundoscopic examination showed a calcified mass in the right eye with total retinal detachment, and an endophytic mass at the posterior pole of the left eye without vitreous seeding.
FIGURE 1. A, The recurrent tumor in nasal cavity shows sheets of small round cells with rosettes (hematoxylin and eosin, magnification: 400). B, This tumor was robustly immunoreactive for synaptophysin (snaptophysin immunohistochemistry, magnification: 400).
Received for publication August 21, 2014; accepted January 25, 2015. From the Departments of *Pediatrics; yOphthalmology; 8Pathology; zRadiology, Seoul National University College of Medicine; wCancer Research Institute, Seoul National University; and zDepartment of Pediatrics, Seoul National University Boramae Medical Center, Seoul, Korea. The authors declare no conflict of interest. Supported by a grant (14172MFDS178) from Ministry of Food and Drug Safety in 2014. Reprints: Hee Young Shin, MD, PhD, Seoul National University Children’s Hospital, 103 Daehak-ro, Jongno-gu, Seoul 110-799, Korea (e-mail: [email protected]). Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
e264 | www.jpho-online.com
J Pediatr Hematol Oncol
Volume 37, Number 4, May 2015
J Pediatr Hematol Oncol
Volume 37, Number 4, May 2015
Very Late Relapse of Bilateral Retinoblastoma
FIGURE 2. A, Magnetic resonance imaging (MRI) after relapse showing a mass involving the nasal cavity, ethmoid, and sphenoid and maxillary sinuses, with intracranial extension into the right medial orbit. B, Positron emission tomography showing multiple metastases to the vertebral bodies and neck lymph nodes. C, MRI showing the disappearance of the relapsed tumors after high-dose chemotherapy and autologous stem cell transplantation. Bone scan showed no evidence of bone metastasis. Bone marrow aspiration and cerebrospinal fluid examination showed no neoplastic cells. There was no familial history of retinoblastoma. The diagnosis of bilateral retinoblastoma was confirmed by clinical features and diagnostic workup. The patient was initially treated with CDDP + VPO regimen consisting of cisplatin (3 mg/kg for 1 d), etoposide (5 mg/kg for 2 d), and vincristine (1.5 mg/m2 for 1 d) every 3 weeks. Enucleation of the right eye was performed after
Copyright
r
2 cycles of neoadjuvant chemotherapy. Pathology of the right eye revealed a 1 cm2 endophytic retinoblastoma with optic nerve head involvement. The tumor was resected with a clear margin and no retrolaminar optic nerve invasion. The tumor in the right eye was classified as group E and in the left eye as group B by the International Classification of Retinoblastoma (ICRB), respectively. Focal diode laser therapy of the left eye was performed 2 times with examination under anesthesia. A total of 13 cycles of CDDP +
2015 Wolters Kluwer Health, Inc. All rights reserved.
www.jpho-online.com |
e265
J Pediatr Hematol Oncol
Choi et al
VPO chemotherapy were administered. Febrile neutropenia was the only short-term complication during chemotherapy. Six months after completion of chemotherapy, brain magnetic resonance imaging showed no evidence of recurrence or intracranial metastasis. Fundus examination in the left eye showed a flat atrophic scar. The patient underwent regular examination under anesthesia to monitor disease recurrence. Bilateral high-tone hearing loss was detected by audiogram 11 years and 9 months after completion of chemotherapy. Thirteen years and 8 months after completion of treatment, otolaryngologic evaluation was performed for recurrent epistaxis and rhinitis that persisted for 1 month; this evaluation revealed a new mass in the nasal cavity. A biopsy was performed to determine whether the mass was a relapse or a secondary malignancy, and the result was consistent with metastatic retinoblastoma. Histopathologically, it was composed of sheet of small round cells with some Flexner-Wintersteiner rosettes, high mitoses, apoptosis, and necrosis. The tumor was robustly immunoreactive for synapatophysin (polyclonal, 1:200, catalog no. 18-0130; Invitrogen) and CD56 (neuronal cell adhesion molecule) (1:300, clone 123C3; Zymed) and weakly positive for chromogranin (1:300, catalog no. 18-0094; Invitrogen) (Fig. 1). Computed tomography and magnetic resonance imaging revealed a 4.5 5.8 5.5 cm, heterogenous, lowattenuating mass involving the entire nasal cavity, ethmoid, sphenoid, and right maxillary sinuses, and right medial orbit, with intracranial extension (Fig. 2A). Bone scan and positron emission tomography showed evidence of level II metastatic lymphadenopathy in the right cervical chain. In addition, bone metastatic lesions in the first, third, and fifth lumbar vertebrae as well as the seventh thoracic vertebra were observed (Fig. 2B). No retinoblastoma cells were noted in the cerebrospinal fluid or bone marrow. Retinoblastoma-1 gene sequencing was performed and a novel pathogenic variant, c.869delA, was detected. The patient’s parents and brother did not have the mutation. The patient was hospitalized for chemotherapy treatment, and hyponatremia was detected in prechemotherapy laboratory analysis. We administered fluid management to treat suspected syndrome of inappropriate antidiuretic hormone secretion. The patient was treated for relapsed retinoblastoma with 6 cycles of CarDEC regimen consisting of carboplatin (450 mg/m2 for 1 d), etoposide (100 mg/m2 for 2 d), doxorubicin (30 mg/m2 for 1 d), cyclophosphamide (30 mg/kg for 2 d), and vincristine (2 mg/m2 for 1 d). The following 3-drug regimen was also intrathecally administered 6 times: methotrexate 15 mg, cytarabine 30 mg, and hydrocortisone 15 mg. After 5 cycles of the CarDEC regimen, the patient received cyclophosphamide (1000 mg/m2 for 3 d), etoposide (150 mg/m2 for 3 d), and filgrastim for peripheral blood stem cell mobilization. However, the number of cells for autologous stem cell transplantation (ASCT) was inadequate. Mobilization was successful using plerixafor plus filgrastim. High-dose chemotherapy with carboplatin (500 mg/m2 on days 8, 7, 6), thiotepa (300 mg/m2 on days 5, 4, 3), and etoposide (250 mg/m2 on days 5, 4, 3) was administered followed by ASCT. The patient had febrile neutropenia and hypotension, but culture studies revealed no microorganisms. Engraftment of neutrophils and platelets was noted on day 12 and 42 after ASCT, respectively. After ASCT, the patient was in continuous second remission with a follow-up duration of 7 months (Fig. 2C).
DISCUSSION In this case, the patient was diagnosed with bilateral retinoblastoma at 6 months of age. Patients with bilateral retinoblastoma usually require systemic chemotherapy and focal consolidation therapies. Approximately 60% of patients require enucleation of 1 eye that has more advanced stage.5–7 The patient underwent enucleation of the right eye, local laser therapy for the left eye, and neoadjuvant and adjuvant chemotherapy. Because of the very poor outcomes associated with extraocular retinoblastoma, researchers have tried to find
e266 | www.jpho-online.com
Volume 37, Number 4, May 2015
predictors for extraocular relapse.8 High-risk histopathologic features include tumor invasion of the anterior chamber, retrolaminar optic nerve, choroid invasion, sclera, and orbit.9 Chantada et al10 reported that sclera invasion is significantly associated with extraocular relapse following enucleation. The patient’s right eye was classified as group E by ICRB, but she had no high-risk histopathologic features. Jubran et al8 demonstrated that all patients need close follow-up regardless of histopathologic risk factors. For patients with retinoblastoma, the risk of recurrent or new tumors declines with age.11 Relapse almost always occurs within the first few years, and most commonly within the first 2 years after treatment completion.3,6,7,12 De Jong et al2 reported a rare case of retinoblastoma that developed in the contralateral eye 25 years after enucleation of the affected eye, and they believed it to be attributable to the patient’s rare mutation rather than a recurrence of retinoblastoma. In the current case, the patient was in complete remission for >10 years, during which she underwent regular evaluations by a pediatrician and an ophthalmologist. However, the patient experienced extraocular relapse 13 years and 8 months after completing treatment. The weakness of this report is not to perform molecular studies to show the clonality of primary intraocular mass and new tumor. However, it was likely that the tumor was metastatic retinoblastoma rather than secondary malignancy when reviewing the pathologic findings. This case report is significant because it documents the longest reported time to recurrence for this disease. In conclusion, patients who have been treated for extensive retinoblastoma need continuous and careful evaluation for late relapse, even though complete remission was achieved for first several years. The survival rate for retinoblastoma has improved significantly over the past few decades. In addition, lifespan after treatment for retinoblastoma is long because it is a childhood disease. Therefore, it is important that clinicians and patients treated for retinoblastoma are aware of the possibility of late relapse, regardless of high-risk pathologic features. In addition, if the recurrence is suspected, orbit or brain imaging studies should be performed immediately. Future large-scale studies with longer follow-up durations are needed.
REFERENCES 1. Chintagumpala M, Chevez-Barrios P, Paysse EA, et al. Retinoblastoma: review of current management. Oncologist. 2007;12:1237–1246. 2. de Jong PT, Mooy CM, Stoter G, et al. Late-onset retinoblastoma in a well-functioning fellow eye. Ophthalmology. 2006;113:1040–1044. 3. Kim JW, Kathpalia V, Dunkel IJ, et al. Orbital recurrence of retinoblastoma following enucleation. Br J Ophthalmol. 2009;93:463–467. 4. Goto H, Kousaka A, Takano S, et al. Recurrence of retinoblastoma 12 years after brachytherapy. Am J Ophthalmol. 2002;134:773–775. 5. Shields CL, Honavar SG, Meadows AT, et al. Chemoreduction plus focal therapy for retinoblastoma: factors predictive of need for treatment with external beam radiotherapy or enucleation. Am J Ophthalmol. 2002;133:657–664. 6. Shields CL, Honavar SG, Shields JA, et al. Factors predictive of recurrence of retinal tumors, vitreous seeds, and subretinal seeds following chemoreduction for retinoblastoma. Arch Ophthalmol. 2002;120:460–464.
Copyright
r
2015 Wolters Kluwer Health, Inc. All rights reserved.
J Pediatr Hematol Oncol
Volume 37, Number 4, May 2015
7. Shields CL, Mashayekhi A, Cater J, et al. Chemoreduction for retinoblastoma. Analysis of tumor control and risks for recurrence in 457 tumors. Am J Ophthalmol. 2004;138:329–337. 8. Jubran RF, Erdreich-Epstein A, Butturini A, et al. Approaches to treatment for extraocular retinoblastoma: Children’s Hospital Los Angeles experience. J Pediatr Hematol Oncol. 2004;26:31–34. 9. Eagle RC Jr. High-risk features and tumor differentiation in retinoblastoma: a retrospective histopathologic study. Arch Pathol Lab Med. 2009;133:1203–1209.
Copyright
r
Very Late Relapse of Bilateral Retinoblastoma
10. Chantada GL, Dunkel IJ, Antoneli CB, et al. Risk factors for extraocular relapse following enucleation after failure of chemoreduction in retinoblastoma. Pediatr Blood Cancer. 2007;49:256–260. 11. Berman EL, Donaldson CE, Giblin M, et al. Outcomes in retinoblastoma, 1974-2005: the Children’s Hospital, Westmead. Clin Experiment Ophthalmol. 2007;35:5–12. 12. Shields CL, Meadows AT, Leahey AM, et al. Continuing challenges in the management of retinoblastoma with chemotherapy. Retina. 2004;24:849–862.
2015 Wolters Kluwer Health, Inc. All rights reserved.
www.jpho-online.com |
e267
AND
LABORATORY OBSERVATIONS
Very Late Relapse of Bilateral Retinoblastoma Jung Yoon Choi, MD,*w Hyoung Jin Kang, MD, PhD,*w Ji Won Lee, MD, PhD,*w Hee Young Ju, MD,*w Che Ry Hong, MD,*w Hyery Kim, MD, PhD,wz Young Suk Yu, MD, PhD,y Sung-Hye Park, MD, PhD,8 Jung-Eun Cheon, MD, PhD,z Kyung Duk Park, MD, PhD,*w and Hee Young Shin, MD, PhD*w
Summary: Retinoblastoma usually recurs within the first few years after treatment completion. We report a rare case of very late relapse in a 6-month-old girl who was diagnosed with bilateral retinoblastoma. The patient achieved first remission after treatment with neoadjuvant chemotherapy, enucleation of the right eye, local laser therapy of the left eye, and adjuvant chemotherapy. Extraocular relapse with multiple metastases occurred 13 years and 8 months after treatment. The patient is currently in second complete remission after receiving high-dose chemotherapy and autologous stem cell transplantation. In conclusion, long-term follow-up is needed for early detection of recurrent retinoblastoma. Key Words: retinoblastoma, recurrence, enucleation
(J Pediatr Hematol Oncol 2015;37:e264–e267)
R
etinoblastoma is the most common intraocular malignancy in childhood. Most retinoblastoma patients are diagnosed before 3 years of age. Bilateral retinoblastoma comprises 20% to 30% of all retinoblastoma cases, and usually presents at a younger age than unilateral disease.1
Because most patients with retinoblastoma are young, close observation for long-term complications including relapse is important for improving survival and quality of life. There are few reports of long-term follow-up >10 years after completion of treatment.2–4 We describe a case of bilateral retinoblastoma in a 6-month-old female who experienced a very late relapse at 13 years and 8 months posttherapy.
ETHICS STATEMENT This study was approved by the institutional review boards of the Seoul National University Hospital, Seoul, Korea (IRB number: 1408-032-600). Informed consent was waived by the board.
CASE REPORT A 6-month-old female was referred to our institution for leukocoria and divergent strabismus in both eyes. Computed tomography and fundoscopic examination showed a calcified mass in the right eye with total retinal detachment, and an endophytic mass at the posterior pole of the left eye without vitreous seeding.
FIGURE 1. A, The recurrent tumor in nasal cavity shows sheets of small round cells with rosettes (hematoxylin and eosin, magnification: 400). B, This tumor was robustly immunoreactive for synaptophysin (snaptophysin immunohistochemistry, magnification: 400).
Received for publication August 21, 2014; accepted January 25, 2015. From the Departments of *Pediatrics; yOphthalmology; 8Pathology; zRadiology, Seoul National University College of Medicine; wCancer Research Institute, Seoul National University; and zDepartment of Pediatrics, Seoul National University Boramae Medical Center, Seoul, Korea. The authors declare no conflict of interest. Supported by a grant (14172MFDS178) from Ministry of Food and Drug Safety in 2014. Reprints: Hee Young Shin, MD, PhD, Seoul National University Children’s Hospital, 103 Daehak-ro, Jongno-gu, Seoul 110-799, Korea (e-mail: [email protected]). Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
e264 | www.jpho-online.com
J Pediatr Hematol Oncol
Volume 37, Number 4, May 2015
J Pediatr Hematol Oncol
Volume 37, Number 4, May 2015
Very Late Relapse of Bilateral Retinoblastoma
FIGURE 2. A, Magnetic resonance imaging (MRI) after relapse showing a mass involving the nasal cavity, ethmoid, and sphenoid and maxillary sinuses, with intracranial extension into the right medial orbit. B, Positron emission tomography showing multiple metastases to the vertebral bodies and neck lymph nodes. C, MRI showing the disappearance of the relapsed tumors after high-dose chemotherapy and autologous stem cell transplantation. Bone scan showed no evidence of bone metastasis. Bone marrow aspiration and cerebrospinal fluid examination showed no neoplastic cells. There was no familial history of retinoblastoma. The diagnosis of bilateral retinoblastoma was confirmed by clinical features and diagnostic workup. The patient was initially treated with CDDP + VPO regimen consisting of cisplatin (3 mg/kg for 1 d), etoposide (5 mg/kg for 2 d), and vincristine (1.5 mg/m2 for 1 d) every 3 weeks. Enucleation of the right eye was performed after
Copyright
r
2 cycles of neoadjuvant chemotherapy. Pathology of the right eye revealed a 1 cm2 endophytic retinoblastoma with optic nerve head involvement. The tumor was resected with a clear margin and no retrolaminar optic nerve invasion. The tumor in the right eye was classified as group E and in the left eye as group B by the International Classification of Retinoblastoma (ICRB), respectively. Focal diode laser therapy of the left eye was performed 2 times with examination under anesthesia. A total of 13 cycles of CDDP +
2015 Wolters Kluwer Health, Inc. All rights reserved.
www.jpho-online.com |
e265
J Pediatr Hematol Oncol
Choi et al
VPO chemotherapy were administered. Febrile neutropenia was the only short-term complication during chemotherapy. Six months after completion of chemotherapy, brain magnetic resonance imaging showed no evidence of recurrence or intracranial metastasis. Fundus examination in the left eye showed a flat atrophic scar. The patient underwent regular examination under anesthesia to monitor disease recurrence. Bilateral high-tone hearing loss was detected by audiogram 11 years and 9 months after completion of chemotherapy. Thirteen years and 8 months after completion of treatment, otolaryngologic evaluation was performed for recurrent epistaxis and rhinitis that persisted for 1 month; this evaluation revealed a new mass in the nasal cavity. A biopsy was performed to determine whether the mass was a relapse or a secondary malignancy, and the result was consistent with metastatic retinoblastoma. Histopathologically, it was composed of sheet of small round cells with some Flexner-Wintersteiner rosettes, high mitoses, apoptosis, and necrosis. The tumor was robustly immunoreactive for synapatophysin (polyclonal, 1:200, catalog no. 18-0130; Invitrogen) and CD56 (neuronal cell adhesion molecule) (1:300, clone 123C3; Zymed) and weakly positive for chromogranin (1:300, catalog no. 18-0094; Invitrogen) (Fig. 1). Computed tomography and magnetic resonance imaging revealed a 4.5 5.8 5.5 cm, heterogenous, lowattenuating mass involving the entire nasal cavity, ethmoid, sphenoid, and right maxillary sinuses, and right medial orbit, with intracranial extension (Fig. 2A). Bone scan and positron emission tomography showed evidence of level II metastatic lymphadenopathy in the right cervical chain. In addition, bone metastatic lesions in the first, third, and fifth lumbar vertebrae as well as the seventh thoracic vertebra were observed (Fig. 2B). No retinoblastoma cells were noted in the cerebrospinal fluid or bone marrow. Retinoblastoma-1 gene sequencing was performed and a novel pathogenic variant, c.869delA, was detected. The patient’s parents and brother did not have the mutation. The patient was hospitalized for chemotherapy treatment, and hyponatremia was detected in prechemotherapy laboratory analysis. We administered fluid management to treat suspected syndrome of inappropriate antidiuretic hormone secretion. The patient was treated for relapsed retinoblastoma with 6 cycles of CarDEC regimen consisting of carboplatin (450 mg/m2 for 1 d), etoposide (100 mg/m2 for 2 d), doxorubicin (30 mg/m2 for 1 d), cyclophosphamide (30 mg/kg for 2 d), and vincristine (2 mg/m2 for 1 d). The following 3-drug regimen was also intrathecally administered 6 times: methotrexate 15 mg, cytarabine 30 mg, and hydrocortisone 15 mg. After 5 cycles of the CarDEC regimen, the patient received cyclophosphamide (1000 mg/m2 for 3 d), etoposide (150 mg/m2 for 3 d), and filgrastim for peripheral blood stem cell mobilization. However, the number of cells for autologous stem cell transplantation (ASCT) was inadequate. Mobilization was successful using plerixafor plus filgrastim. High-dose chemotherapy with carboplatin (500 mg/m2 on days 8, 7, 6), thiotepa (300 mg/m2 on days 5, 4, 3), and etoposide (250 mg/m2 on days 5, 4, 3) was administered followed by ASCT. The patient had febrile neutropenia and hypotension, but culture studies revealed no microorganisms. Engraftment of neutrophils and platelets was noted on day 12 and 42 after ASCT, respectively. After ASCT, the patient was in continuous second remission with a follow-up duration of 7 months (Fig. 2C).
DISCUSSION In this case, the patient was diagnosed with bilateral retinoblastoma at 6 months of age. Patients with bilateral retinoblastoma usually require systemic chemotherapy and focal consolidation therapies. Approximately 60% of patients require enucleation of 1 eye that has more advanced stage.5–7 The patient underwent enucleation of the right eye, local laser therapy for the left eye, and neoadjuvant and adjuvant chemotherapy. Because of the very poor outcomes associated with extraocular retinoblastoma, researchers have tried to find
e266 | www.jpho-online.com
Volume 37, Number 4, May 2015
predictors for extraocular relapse.8 High-risk histopathologic features include tumor invasion of the anterior chamber, retrolaminar optic nerve, choroid invasion, sclera, and orbit.9 Chantada et al10 reported that sclera invasion is significantly associated with extraocular relapse following enucleation. The patient’s right eye was classified as group E by ICRB, but she had no high-risk histopathologic features. Jubran et al8 demonstrated that all patients need close follow-up regardless of histopathologic risk factors. For patients with retinoblastoma, the risk of recurrent or new tumors declines with age.11 Relapse almost always occurs within the first few years, and most commonly within the first 2 years after treatment completion.3,6,7,12 De Jong et al2 reported a rare case of retinoblastoma that developed in the contralateral eye 25 years after enucleation of the affected eye, and they believed it to be attributable to the patient’s rare mutation rather than a recurrence of retinoblastoma. In the current case, the patient was in complete remission for >10 years, during which she underwent regular evaluations by a pediatrician and an ophthalmologist. However, the patient experienced extraocular relapse 13 years and 8 months after completing treatment. The weakness of this report is not to perform molecular studies to show the clonality of primary intraocular mass and new tumor. However, it was likely that the tumor was metastatic retinoblastoma rather than secondary malignancy when reviewing the pathologic findings. This case report is significant because it documents the longest reported time to recurrence for this disease. In conclusion, patients who have been treated for extensive retinoblastoma need continuous and careful evaluation for late relapse, even though complete remission was achieved for first several years. The survival rate for retinoblastoma has improved significantly over the past few decades. In addition, lifespan after treatment for retinoblastoma is long because it is a childhood disease. Therefore, it is important that clinicians and patients treated for retinoblastoma are aware of the possibility of late relapse, regardless of high-risk pathologic features. In addition, if the recurrence is suspected, orbit or brain imaging studies should be performed immediately. Future large-scale studies with longer follow-up durations are needed.
REFERENCES 1. Chintagumpala M, Chevez-Barrios P, Paysse EA, et al. Retinoblastoma: review of current management. Oncologist. 2007;12:1237–1246. 2. de Jong PT, Mooy CM, Stoter G, et al. Late-onset retinoblastoma in a well-functioning fellow eye. Ophthalmology. 2006;113:1040–1044. 3. Kim JW, Kathpalia V, Dunkel IJ, et al. Orbital recurrence of retinoblastoma following enucleation. Br J Ophthalmol. 2009;93:463–467. 4. Goto H, Kousaka A, Takano S, et al. Recurrence of retinoblastoma 12 years after brachytherapy. Am J Ophthalmol. 2002;134:773–775. 5. Shields CL, Honavar SG, Meadows AT, et al. Chemoreduction plus focal therapy for retinoblastoma: factors predictive of need for treatment with external beam radiotherapy or enucleation. Am J Ophthalmol. 2002;133:657–664. 6. Shields CL, Honavar SG, Shields JA, et al. Factors predictive of recurrence of retinal tumors, vitreous seeds, and subretinal seeds following chemoreduction for retinoblastoma. Arch Ophthalmol. 2002;120:460–464.
Copyright
r
2015 Wolters Kluwer Health, Inc. All rights reserved.
J Pediatr Hematol Oncol
Volume 37, Number 4, May 2015
7. Shields CL, Mashayekhi A, Cater J, et al. Chemoreduction for retinoblastoma. Analysis of tumor control and risks for recurrence in 457 tumors. Am J Ophthalmol. 2004;138:329–337. 8. Jubran RF, Erdreich-Epstein A, Butturini A, et al. Approaches to treatment for extraocular retinoblastoma: Children’s Hospital Los Angeles experience. J Pediatr Hematol Oncol. 2004;26:31–34. 9. Eagle RC Jr. High-risk features and tumor differentiation in retinoblastoma: a retrospective histopathologic study. Arch Pathol Lab Med. 2009;133:1203–1209.
Copyright
r
Very Late Relapse of Bilateral Retinoblastoma
10. Chantada GL, Dunkel IJ, Antoneli CB, et al. Risk factors for extraocular relapse following enucleation after failure of chemoreduction in retinoblastoma. Pediatr Blood Cancer. 2007;49:256–260. 11. Berman EL, Donaldson CE, Giblin M, et al. Outcomes in retinoblastoma, 1974-2005: the Children’s Hospital, Westmead. Clin Experiment Ophthalmol. 2007;35:5–12. 12. Shields CL, Meadows AT, Leahey AM, et al. Continuing challenges in the management of retinoblastoma with chemotherapy. Retina. 2004;24:849–862.
2015 Wolters Kluwer Health, Inc. All rights reserved.
www.jpho-online.com |
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