The management of retinoblastoma Fabian, Ido D; Onadim, Zerrin; Karaa, Esin ...
Oncogene,
03/2018, Letnik:
37, Številka:
12
Journal Article
Recenzirano
Retinoblastoma (Rb) is the most common primary intraocular malignancy of childhood, but an uncommon paediatric cancer, with a constant incidence worldwide of 1:15,000-1:20,000 live births. Despite ...its rarity, Rb has served as a cornerstone in the field of oncology in many of the aspects that comprise cancer management, including classification schemes, treatment modalities, genetic testing and screening. Until just over half a century ago, the major treatment for Rb was eye removal, and prognosis was poor with outcome fatal for most children. The dramatic evolution, in a short period of time across all fields of Rb management, as well as the development of specialized centres, better infrastructure and introduction of awareness campaigns, has resulted in nearly 100% survival in developed countries and allowed eye salvage in many of the cases. External beam radiotherapy was used as the main treatment choice for four decades, but replaced by chemotherapy at the turn of the century. Initially, and still in many centres, chemotherapy is administered intravenously, but recently is targeted directly into the eye by means of intra-ophthalmic artery and intravitreal chemotherapy. To date, a range of treatments is available to the Rb expert, including enucleation, but there is lack of consensus in a number of scenarios as to what to use and when. In such a rare cancer, treatment outcomes are reported usually via retrospective analyses, with few prospective randomized controlled trials. Classification schemes have also evolved following the introduction of new treatment modalities, but discrepancies exist among centres with respect to the preferred schema and its interpretation. Retinoblastoma management is a remarkable success story, but the future will require a collaborative effort in the form of multicentre randomized controlled trials in order to further improve the quality of care for this subset of young children with ocular cancer.
To report the efficacy of super-selective intra-ophthalmic artery melphalan (IAM) for the treatment of refractory retinoblastoma and any associated complications of this treatment.
A prospective case ...series.
Eyes with retinoblastoma that had been treated with systemic chemotherapy or local therapy and had a relapse of their condition.
All patients receiving IAM between May 2009 and September 2010 were included in the study. Intra-ophthalmic artery melphalan was offered to patients who had failed to respond adequately to systemic chemotherapy and local treatment where appropriate or because of a new recurrence of retinoblastoma that could not be treated with local therapies. None of the patients were excluded because of central nervous system abnormalities. Patients received 2 treatments of IAM given 4 weeks apart. All patients received an orthoptic assessment 3 weeks after each treatment and an examination under anesthesia (EUA). A third treatment was given if an unsatisfactory response was observed on EUA after 2 treatments.
The response of the retinoblastoma tumor(s) and any associated local side effects from the treatment.
A total of 15 eyes in 14 patients were treated with IAM during the study period. The mean age at the time of IAM was 31.5 months (median 17.3, range 11.2-150.7 months), and the mean follow-up was 8.7 months (3-16.3 months). Tumor control was achieved in 12 eyes (80%), and 12 eyes (80%) had local side effects that included third cranial nerve palsy in 6 (40%), orbital edema in 3 (20%), permanent retinal detachment in 1 (7%), and vitreous hemorrhage in 4 (27%). Seven eyes (47%) developed significant retinal pigment epithelium changes.
Intra-ophthalmic artery melphalan is an effective treatment for retinoblastoma, achieving a high level of remission in refractory tumors. It can be associated with significant local side effects that can result in loss of vision and possible amblyogenesis. Clinicians and parents need to consider the benefits and potential local side effects before embarking on treatment.
To evaluate the rate and identify the risk factors for high-risk histopathologic features in group D retinoblastoma eyes enucleated as primary or secondary treatment.
Retrospective analysis.
A total ...of 64 enucleated group D eyes (62 patients), of which 40 (40 patients) were primary and 24 (22 patients) were secondary to other treatments.
Clinicopathologic correlation of consecutive group D eyes enucleated from 2002 to 2014. High-risk histopathologic features were defined as the presence of anterior chamber seeds, iris infiltration, ciliary body/muscle infiltration, massive (≥3 mm) choroidal invasion, retrolaminar optic nerve invasion, or combined non-massive choroidal and prelaminar/laminar optic nerve invasion.
High-risk histopathologic features, metastasis, and death.
Of the 64 group D eyes, 37 (58%) were classified as cT2bN0M0H0, 24 (38%) were classified as cT2bN0M0H1, and 3 (5%) were classified as cT2aN0M0H1, according to the 8th edition cTNMH Retinoblastoma Staging. High-risk histopathologic features were detected in 10 eyes (16%) in the entire cohort, 5 eyes (13%) of the primary enucleated group (pT3aNxM0, n = 2 and pT3bNxM0, n = 3, 8th edition pTNM), and 5 eyes (21%) of the secondary enucleated group (pT2bNxM0, n = 2, pT3aNxM0, n = 2 and pT3cNxM0, n = 1). Absence of vitreous seeds at presentation was the only predictive factor found for high-risk histopathologic features in the primary enucleation group (P = 0.042), whereas none were found in the secondary group (P ≥ 0.179). Invasion of the anterior structures (anterior chamber, iris, ciliary body/muscle) was detected significantly more after secondary enucleation (P = 0.048). All patients with high-risk histopathologic features were treated with adjuvant chemotherapy, and no metastases were recorded in a median follow-up time of 73.2 months (mean, 71.5; range, 13.7-153.0).
The choice of primary treatment for group D retinoblastoma should be carefully weighed, because according to this study, 13% of eyes harbor high-risk histopathologic features at presentation, with the absence of vitreous seeds being a potential risk factor. It is of special importance in group D eyes being considered for nonsystemic treatment, such as primary intraophthalmic artery chemotherapy. Secondary enucleated group D eyes with high-risk histopathologic features more commonly involved anterior structures, warranting meticulous clinical and histologic examinations for this subset of patients.
Retinoblastoma (RB) is the most common intraocular pediatric cancer. Nearly all cases of RB are associated with mutations compromising the function of the RB1 tumor suppressor gene. We previously ...demonstrated that PRELP is widely downregulated in various cancers and our in vivo and in vitro analysis revealed PRELP as a novel tumor suppressor and regulator of EMT. In addition, PRELP is located at chromosome 1q31.1, around a region hypothesized to be associated with the initiation of malignancy in RB. Therefore, in this study, we investigated the role of PRELP in RB through in vitro analysis and next-generation sequencing. Immunostaining revealed that PRELP is expressed in Müller glial cells in the retina. mRNA expression profiling of PRELP−/− mouse retina and PRELP-treated RB cells found that PRELP contributes to RB progression via regulation of the cancer microenvironment, in which loss of PRELP reduces cell–cell adhesion and facilitates EMT. Our observations suggest that PRELP may have potential as a new strategy for RB treatment.
Objective To develop an algorithm that allows advanced identification of infants requiring treatment for retinopathy of prematurity (ROP). Study design A retrospective observational study was ...performed at 2 tertiary neonatal units serving a multiethnic population in the UK, using data on 929 infants eligible for ROP screening. The relationships between study variables and the risk of developing ROP requiring treatment were analyzed using multiple logistic regression. Results After applying exclusion criteria, data from 589 infants were analyzed; of these, 57 required laser treatment. The proportion of treated infants was 5.9% of those born to black mothers, 9.39% of those born to white mothers, and 12.8% of those born to Asian mothers ( P = .047). Multiple logistic regression showed that gestational age, birth weight, maternal ethnicity, and early weight gain were predictors for the development of ROP requiring treatment, with maternal ethnicity having greater predictive power compared with early weight gain. We developed an algorithm for predicting the development of ROP requiring treatment with sensitivity, specificity, and positive and negative predictive values of 100%, 65.7%, 23.8%, and 100%, respectively. Conclusion Gestational age, birth weight, early weight gain, and maternal ethnicity are important predictors for the development of ROP requiring treatment. In a multiethnic population, an algorithm to predict development of ROP requiring treatment should include maternal ethnicity. If confirmed through prospective studies, this algorithm could reduce the number of opthalmologic examinations performed for ROP screening.
Retinoblastoma and vision Warda, Omar; Naeem, Zishan; Roelofs, Kelsey A ...
Eye (London),
04/2023, Letnik:
37, Številka:
5
Journal Article
Recenzirano
Odprti dostop
The assessment of vision has a growing importance in the management of retinoblastoma in the era of globe-conserving therapy, both prior to and after treatment. As survival rates approach 98-99% and ...globe salvage rates reach ever-higher levels, it is important to provide families with information regarding the visual outcomes of different treatments. We present an overview of the role of vision in determining the treatment given and the impact of complications of treatment. We also discuss screening and treatment strategies that can be used to maximise vision.
The identification of somatic
variation is crucial to confirm the heritability of retinoblastoma. We and others have previously shown that, when tumour DNA is unavailable, cell-free DNA (cfDNA) ...derived from aqueous humour (AH) can be used to identify somatic
pathogenic variation. Here we report
pathogenic variant detection, as well as cfDNA concentration in an extended cohort of 75 AH samples from 68 patients. We show cfDNA concentration is highly variable and significantly correlated with the collection point of the AH. Cell-free DNA concentrations above 5 pg/µL enabled the detection of 93% of known or expected
pathogenic variants. In AH samples collected during intravitreal chemotherapy treatment (Tx), the yield of cfDNA above 5 pg/µL and subsequent variant detection was low (≤46%). However, AH collected by an anterior chamber tap after one to three cycles of primary chemotherapy (Dx1+) enabled the detection of 75% of expected pathogenic variants. Further limiting our analysis to Dx1+ samples taken after ≤2 cycles (Dx ≤ 2) provided measurable levels of cfDNA in all cases, and a subsequent variant detection rate of 95%. Early AH sampling is therefore likely to be important in maximising cfDNA concentration and the subsequent detection of somatic
pathogenic variants in retinoblastoma patients undergoing conservative treatment.
Abstract Purpose To analyse the long-term visual acuity, strabismus and nystagmus outcomes in Group D retinoblastoma following multimodality treatments in a national retinoblastoma referral centre. ...Design Retrospective interventional case series. Methods A 13-year retrospective chart review of Group D eyes treated initially with intravenous chemotherapy (IVC) and followed-up for at least 1 year from last treatment. Risk factors for final visual acuity (VA) were analysed, and rate of strabismus and nystagmus at last follow-up visit were calculated. Results One hundred and four Group D eyes (92 patients) presented to our centre during the study period, of which 32 (27 patients) met the inclusion criteria. Following IVC (vincristine, etoposide and carboplatin), adjuvant treatments included intra-ophthalmic artery chemotherapy in 5 (16%) eyes, plaque brachytherapy in 5 (16%), transpupillary thermotherapy (TTT) in 18 (56%) and cryotherapy in 24 (75%) eyes. On last examination, 64.41 ± 6.76 months from presentation, mean final VA was 20/283 (logMAR equivalent of 1.15±0.15). On univariate analysis, presentation age, foveal retinoblastoma (at initial examination), use of TTT and tumour-foveola distance (at last visit) were found to be significant risk factors for worse VA (p<0.026). On multivariate analysis, however, only TTT was found to be significant (p=0.010). At last visit, 6/27 (22%) patients had nystagmus and 12/20 (60%) of bilaterally salvaged patients had strabismus (n=10 exotropia and n=2 esotropia). Conclusions Following multimodality treatments initiated with IVC, 50% of salvaged Group D retinoblastoma eyes had <20/200 vision, with TTT being a risk factor for worse vision, 60% had strabismus and 22% nystagmus.
Adjuvant use of laser with systemic chemotherapy for treatment of retinoblastoma may reduce recurrence rates while also causing local side effects. Information is lacking on the effect of laser on ...visual outcomes.
A retrospective review of two retinoblastoma centres in the United Kingdom was conducted. Patients were included if there was a macular tumour in at least one eye. Eyes that received chemotherapy alone were compared with eyes that received chemotherapy plus adjuvant laser.
A total of 76 patients and 91 eyes were included in the study. Systemic chemotherapy alone was used in 71 eyes while chemotherapy plus laser was used in 20 eyes. Demographic characteristics of both groups were similar. Macular relapse rates were similar between groups: 22/71 (31%) eyes in chemotherapy group and 9/20 (45%) eyes in laser group (p=0.29). There was no increase in vitreous relapses in the laser group (2/20 eyes), compared with the chemotherapy group 10/71 eyes (p=0.99). Survival analysis demonstrated similar time to first relapse between groups. Final visual acuity was equal between groups with 6/15 or better present in 31.1% of eyes in the chemotherapy group and 37.5% of eyes in the laser group (p=0.76). Presence of tumour at the fovea was predictive of final visual acuity, regardless of treatment group.
Adjuvant laser in the treatment of retinoblastoma is safe and does not lead to increased rate of vitreous recurrence. Final visual acuity is determined by the presence of tumour at the fovea and not the use of laser.
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