Patients with retinoblastoma and chromosome 13q deletions have increased chemotherapy‐related toxicities

Brennan, Rachel C.; Qaddoumi, Ibrahim; Billups, Catherine A.; Kaluzny, Tracy; Furman, Wayne L.; Wilson, Matthew W.

doi:10.1002/pbc.26138

Cited by 11 publications

(8 citation statements)

References 18 publications

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“…Three out of the four IVC cycles administered to one patient in this study resulted in grade 3‐4 hematologic toxicity, and required three rounds of filgrastim in total. This is consistent with prior literature, which reported increased IVC toxicity for deletion patients without an increase in mortality or treatment failure 9 . The majority of this 13q− cohort's OAC cycles also resulted in hematologic toxicity.…”

Section: Discussionsupporting

confidence: 91%

“…This is consistent with prior literature, which reported increased IVC toxicity for deletion patients without an increase in mortality or treatment failure. 9 The majority of this 13q− cohort's OAC cycles also resulted in hematologic toxicity. Fifteen out of 26 OAC cycles (58%) were associated with grade 3-4 hematologic toxicities, and eight of the 10 patients (80%) who underwent OAC had at least one grade 3-4 toxicity.…”

Section: Discussionmentioning

confidence: 96%

“…Notably, one retrospective review demonstrated that 13q− patients have higher incidence of neutropenia during systemic chemotherapy compared to nondeletion syndrome retinoblastoma patients. 9 Although it is widely believed that these children handle systemic chemotherapy less well, other large studies on chemotherapy treatment toxicity and efficacy for retinoblastoma have not commented on the toxicities/responses of patients with 13q−. [10][11][12] Intra-arterial and intravitreal chemotherapies, two treatment modalities more widely used over the past 15 years, minimize systemic exposure to chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

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Retinoblastoma management in 13q deletion syndrome patients using super‐selective chemotherapies and other cancer‐directed interventions

Cobbs

Francis

Dunkel

et al. 2020

Pediatric Blood & Cancer

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Background This study aimed to identify best practices for treating 13q deletion syndrome (13q−) patients with retinoblastoma in the era of super‐selective ophthalmic artery chemosurgery (OAC) and intravitreal injection therapy (IVIT). Methods Retrospective study of 21 eyes from 14 patients with retinoblastoma and 13q− who were treated at Memorial Sloan Kettering Cancer Center (MSKCC) between May 2006 and May 2020, with a mean follow up of 3.7 years. Ocular survival, patient survival, and treatment toxicities were assessed. Results Nine of the 12 eyes that underwent OAC/IVIT at MSKCC have been progression free for at least 1 year since their last treatments. Fifteen out of 26 OAC cycles resulted in grade 3‐4 hematologic toxicity. There was one death from sepsis in the setting of intravenous chemotherapy (IVC) for metastatic disease that occurred after OAC/IVIT therapy. The 2‐year Kaplan‐Meier ocular survival estimate for the whole cohort was 75% and for the eyes that received OAC or IVIT at MSKCC 83%. For OAC hematologic toxicities, one platelet transfusion and two filgrastim doses were administered, and one patient was hospitalized for neutropenic fevers. Conclusions The majority of 13q− eyes treated with OAC/IVIT‐based regimens can be cured, and there were no deaths related to complications from OAC or IVIT. 13q− Patients did have increased risk of systemic treatment complications, even from super‐selective chemotherapies. Despite these toxicities, only one patient developed febrile neutropenia, one patient required a blood product transfusion, and two patients received filgrastim for both OAC and IVC complications. Précis Children with 13q deletion syndrome with retinoblastoma managed with intra‐arterial and intravitreal chemotherapy have excellent patient and ocular survival with acceptable toxicity.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Retinoblastoma management in 13q deletion syndrome patients using super‐selective chemotherapies and other cancer‐directed interventions

Cobbs

Francis

Dunkel

et al. 2020

Pediatric Blood & Cancer

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“…1p loss and Ch. 13 loss 36 , 37 . Specific associations between chromosome-level abnormalities and other characteristics of group A tumors have not been reported and need further study.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive molecular characterization of pediatric radiation-induced high-grade glioma

DeSisto

Lucas

et al. 2021

Nat Commun

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Radiation-induced high-grade gliomas (RIGs) are an incurable late complication of cranial radiation therapy. We performed DNA methylation profiling, RNA-seq, and DNA sequencing on 32 RIG tumors and an in vitro drug screen in two RIG cell lines. We report that based on DNA methylation, RIGs cluster primarily with the pediatric receptor tyrosine kinase I high-grade glioma subtype. Common copy-number alterations include Chromosome (Ch.) 1p loss/1q gain, and Ch. 13q and Ch. 14q loss; focal alterations include PDGFRA and CDK4 gain and CDKN2A and BCOR loss. Transcriptomically, RIGs comprise a stem-like subgroup with lesser mutation burden and Ch. 1p loss and a pro-inflammatory subgroup with greater mutation burden and depleted DNA repair gene expression. Chromothripsis in several RIG samples is associated with extrachromosomal circular DNA-mediated amplification of PDGFRA and CDK4. Drug screening suggests microtubule inhibitors/stabilizers, DNA-damaging agents, MEK inhibition, and, in the inflammatory subgroup, proteasome inhibitors, as potentially effective therapies.

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“…Broad nasal bridge, short nose with a broad tip, distinct external ears, and muscular hypotonia are some of the apparent clinical findings. Other associations with the syndrome include gastrointestinal tract abnormalities, Rb, and failure to thrive [8].…”

Section: Discussionmentioning

confidence: 99%

Recurrent Sporadic Bilateral Retinoblastoma in a Child with 13q Deletion Syndrome

Baqari

Maab

Asghar

et al. 2020

Cureus

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13q syndrome is a chromosomal abnormality in which there is a pathognomic deletion of the genetic material on the long arm (q) of chromosome 13. Phenotypes of this syndrome are variable depending on the location of the deleted segment. The main manifestations of the syndrome include mental retardation, craniofacial dysmorphism, and increased susceptibility to tumors. We report a unique case of recurrent sporadic bilateral retinoblastoma (Rb) in a fouryear-old boy carrying 13q (q12q14) interstitial deletion, which was treated successfully via enucleation and chemotherapy. Where most patients with familial Rb receive a single mutated Rb1 allele as the 'first hit', a small number of patients encounter interstitial deletion of the long arm of chromosome 13, resulting in the loss of the tumor suppressor Rb1 gene and presenting as sporadic cases.

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Patients with retinoblastoma and chromosome 13q deletions have increased chemotherapy‐related toxicities

Cited by 11 publications

References 18 publications

Retinoblastoma management in 13q deletion syndrome patients using super‐selective chemotherapies and other cancer‐directed interventions

Retinoblastoma management in 13q deletion syndrome patients using super‐selective chemotherapies and other cancer‐directed interventions

Comprehensive molecular characterization of pediatric radiation-induced high-grade glioma

Recurrent Sporadic Bilateral Retinoblastoma in a Child with 13q Deletion Syndrome

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