Multimodal Therapy for Stage III Retinoblastoma (International Retinoblastoma Staging System)

Chawla, Bhavna; Hasan, Muhamad Fahmi; Seth, Rachna; Pathy, Sushmita; Pattebahadur, Rajesh; Sharma, Sanjay; Upadhyaya, Ashish; Azad, Rajvardhan

doi:10.1016/j.ophtha.2016.05.034

Cited by 26 publications

(41 citation statements)

References 18 publications

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“…The overall Kaplan–Meier survival probability was 80% and 42% at 1 year and 4 years, respectively. [55] The Kaplan–Meier survival probability at 1 year was similar in both groups (81% and 79%). However, at 4 years, the survival probability for VEC-treated cases was higher [63% vs. 25%], with a strong trend of better survival over time ( P = 0.05).…”

Section: Extraocular Retinoblastomamentioning

confidence: 88%

“…Recently, a prospective randomized comparative study on 54 cases of Stage III Rb (International Retinoblastoma Staging System)[54] was published from our center. [55] Treatment consisted of a multimodal protocol with NAC, enucleation, orbital EBRT, and adjuvant chemotherapy. For chemotherapy, patients were randomized into two groups; one group was treated with high-dose triple-drug chemotherapy consisting of VEC and the other group with carboplatin and etoposide, alternating with cyclophosphamide, idarubicin, and vincristine (five drugs).…”

Section: Extraocular Retinoblastomamentioning

confidence: 99%

“…The main outcome measures were survival probability, cause of death, and chemotherapy-related toxicity. [55] The mean follow-up was 21.3 months (standard deviation ± 11.34). The overall Kaplan–Meier survival probability was 80% and 42% at 1 year and 4 years, respectively.…”

Section: Extraocular Retinoblastomamentioning

confidence: 99%

“…However, at 4 years, the survival probability for VEC-treated cases was higher [63% vs. 25%], with a strong trend of better survival over time ( P = 0.05). [55] Central nervous system (CNS) metastasis was the most common cause of relapse and death. Two cases in the five drugs' group died due to sepsis following febrile neutropenia.…”

Section: Extraocular Retinoblastomamentioning

confidence: 99%

“…The results of our study showed more effective tumor control and a better safety profile with the VEC protocol, which was recommended as systemic chemotherapy for nonmetastatic orbital Rb. [55]…”

Section: Extraocular Retinoblastomamentioning

confidence: 99%

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Recent advances and challenges in the management of retinoblastoma

Chawla

Singh

2017

Indian J Ophthalmol

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The treatment of retinoblastoma (Rb) has improved significantly in recent times. Worldwide, there is an increasing trend to use conservative treatment modalities that aim to preserve the globe as well as vision with minimum morbidity. Recently, the use of targeted delivery of chemotherapy to the eye in the form of selective intra-arterial and intravitreal chemotherapy has shown promising results. Radiotherapy is beneficial in selected cases, either in the form of plaque brachytherapy or as external beam radiotherapy. Orbital disease carries a poor prognosis for survival. However, a multimodal treatment protocol has improved survival in children with extraocular disease. Nevertheless, challenges remain, especially for the developing world. This review aims to highlight recent advances in the management of Rb that have contributed towards improving treatment outcomes and also discuss the challenges ahead, with special reference to the Indian scenario.

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Section: Extraocular Retinoblastomamentioning

confidence: 88%

Section: Extraocular Retinoblastomamentioning

confidence: 99%

Section: Extraocular Retinoblastomamentioning

confidence: 99%

Section: Extraocular Retinoblastomamentioning

confidence: 99%

Section: Extraocular Retinoblastomamentioning

confidence: 99%

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Recent advances and challenges in the management of retinoblastoma

Chawla

Singh

2017

Indian J Ophthalmol

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Comparison of the pharmacological activity of idarubicin and doxorubicin for retinoblastoma

Zugbi

Winter

Castañon

et al. 2018

Pediatric Blood & Cancer

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Contrary to the infrequency in extraocular disease presentation in high-income countries, extraocular disease can be up to 50% of retinoblastoma cases in low-income countries. 1 Though the prognosis has been improved by the incorporation of intensive multimodality treatments, metastatic retinoblastoma with central nervous system (CNS) involvement is still fatal.Anthracyclines, specifically doxorubicin, have been used and are active 2 for the treatment of extraocular retinoblastoma without CNS invasion though some treatment regimens for high-risk retinoblastoma exclude the use of this class of drugs. 3,4 In the 1990s, we published an upfront phase II window study of idarubicin in patients with extraocular retinoblastoma showing a 60% response rate. 5 Idarubicin is less cardiotoxic compared to doxorubicin, and its higher lipophilicity favors penetration across the blood-brain barrier. The in vivo production of idarubicinol, the main active metabolite equipotent to the parent drug in human tumor cell lines, also favors idarubicin compared with doxorubicin. 6,7 Hence, idarubicin became the anthracycline chosen for prospective studies in our group. 8,9 Despite excellent results with this regimen, its widespread use in other middle-income countries is limited by the poor commercial availability and high costs. Thus, it is debatable whether it would be justified to use idarubicin instead of doxorubicin for patients with high-risk retinoblastoma.Thus, we compared the growth-inhibitory activity of idarubicin and doxorubicin in patient-derived cell lines and the commercial cell line of retinoblastoma Y79. The patient-derived cell lines were established from an intraocular tumor after upfront enucleation of a treatment-naïve patient (HPG-12I) and from the cerebrospinal fluid (CSF) relapsed of a metastatic patient heavily treated (HPG-CSF-1). Cells were exposed to increasing concentrations of drugs, and thereafter cell viability was assessed using MTT. The concentration of doxorubicin or idarubicin that caused a 50% decrease in cell proliferation (IC 50 ) was calculated.Idarubicin IC 50 was 7-to 8-fold lower than the IC 50 of doxorubicin in HPG-CSF-1 and Y79 cell lines (Table 1). However, this difference was smaller in the cell line HPG-12I, in which the IC 50 was 1.7-fold the value for doxorubicin IC 50 in accordance with previous studies that showed the equipotency of both anthracyclines. 10 Assuming a proportional increase in drug exposure with the dose, this result may imply that doxorubicin dosage should be increased 7 to 8 times to obtain a comparable antitumor activity if cells from high-risk patients are considered. Then, for 10 mg/m 2 of idarubicin or the cumulative dosage of 40 mg/m 2 used in the GALOP protocol, each dosage of doxorubicin should be 70 to 80 mg/m 2 , reaching 280 to 320 mg/m 2 for TA B L E 1 Anthracycline cytotoxic activity in retinoblastoma cell lines Cell line/drug Doxorubicin IC 50 , nM (SE) Idarubicin IC 50 , nM (SE) IC 50 ratio Y79 502.6 (1.0) 58.9 (1.1) 8.5 HPG-12I 7.4 (1.1) 4.3 (1.1) 1.7 HPG-...

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Minimally disseminated disease and outcome in overt orbital retinoblastoma

Aschero

Torbidoni

Sampor

et al. 2019

Pediatric Blood & Cancer

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In this retrospective study of patients with overt orbital retinoblastoma, we evaluated minimally disseminated disease (MDD) in bone marrow and cerebrospinal fluid (CSF) using CRX and/or GD2 synthase as markers. Ten patients were evaluated—five (50%) at diagnosis and five upon relapse. MDD was detected in four cases (one in the bone marrow, two in the CSF, and in one case in both sites). All patients received chemotherapy and four received orbital radiotherapy. Seven patients relapsed or progressed and all of them died. Three patients remain in complete remission. There was no apparent correlation between MDD and the outcome.

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Multimodal Therapy for Stage III Retinoblastoma (International Retinoblastoma Staging System)

Cited by 26 publications

References 18 publications

Recent advances and challenges in the management of retinoblastoma

Recent advances and challenges in the management of retinoblastoma

Comparison of the pharmacological activity of idarubicin and doxorubicin for retinoblastoma

Minimally disseminated disease and outcome in overt orbital retinoblastoma

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