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JCO Precision Oncology Feb 2022Soft tissue and bone sarcomas are rare malignancies that exhibit significant pathologic and molecular heterogeneity. Deregulation of the... (Review)
Review
PURPOSE
Soft tissue and bone sarcomas are rare malignancies that exhibit significant pathologic and molecular heterogeneity. Deregulation of the CDKN2A-CCND-CDK4/6-retinoblastoma 1 (Rb) pathway is frequently observed in about 25% of unselected sarcomas and is pathognomonic for specific sarcoma subtypes. This genomic specificity has fueled the clinical evaluation of selective CDK4/6 inhibitors in sarcomas. Here, we highlight successes, opportunities, and future challenges for using CDK4/6 inhibitors to treat sarcoma.
MATERIALS AND METHODS
This review summarizes the current evidence for the use of CDK4/6 inhibitors in sarcoma while identifying molecular rationale and predictive biomarkers that provide the foundation for targeting the CDK4/6 pathway in sarcoma. A systematic review was performed of articles indexed in the PubMed database and the National Institutes of Health Clinical Trials Registry (ClinicalTrials.gov). For each sarcoma subtype, we discuss the preclinical rationale, case reports, and available clinical trials data.
RESULTS
Despite promising clinical outcomes in a subset of sarcomas, resistance to CDK4/6 inhibitors results in highly heterogeneous clinical outcomes. Current clinical data support the use of CDK4/6 inhibitors in subsets of sarcoma primarily driven by CDK4/6 deregulation. When dysregulation of the Rb pathway is a secondary driver of sarcoma, combination therapy with CDK4/6 inhibition may be an option. Developing strategies to identify responders and the mechanisms that drive resistance is important to maximize the clinical utility of these drugs in patients with sarcoma. Potential biomarkers that indicate CDK4/6 inhibitor sensitivity in sarcoma include , , , , , and .
CONCLUSION
CDK4/6 inhibitors represent a major breakthrough for targeted cancer treatment. CDK4/6 inhibitor use in sarcoma has led to limited, but significant, early clinical success. Targeted future clinical research will be key to unlocking the potential of CDK4/6 inhibition in sarcoma.
Topics: Clinical Trials as Topic; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Genomics; Humans; Sarcoma; Soft Tissue Neoplasms; United States
PubMed: 35108033
DOI: 10.1200/PO.21.00211 -
The Lancet. Global Health Mar 2022Despite advancements in globe-preserving treatments, improvements in retinoblastoma outcomes are inconsistent across income levels and geographical locations. We aimed... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite advancements in globe-preserving treatments, improvements in retinoblastoma outcomes are inconsistent across income levels and geographical locations. We aimed to investigate trends in global retinoblastoma survival and globe preservation during the past 40 years. We also examined associated socioeconomic and health-care factors and global survival disparity.
METHODS
We did a systematic review and meta-analysis by screening articles in any language in nine databases (PubMed, Embase, ScienceDirect, Web of Science, OpenGrey, Global Burden of Disease, Global Health Data Exchange, Global Index Medicus, and International Agency for the Prevention of Blindness) published between Jan 1, 1981, and Oct 8, 2021. We screened for articles that described retinoblastoma overall survival or globe salvage, or both. All reported studies were subsequently stratified into four periods: 1980-89, 1990-99, 2000-09, and 2010-20. Indicators on socioeconomic and health-care factors were extracted from the World Bank and WHO. Ophthalmology-related indicators were further parsed from the International Agency for the Prevention of Blindness. Between-study heterogeneities by income level were assessed by mixed-effect meta-analysis. Associations of retinoblastoma outcome with socioeconomic and health-care factors and factors for survival prediction were investigated by multivariable linear regressions. This study is registered with PROSPERO, number CRD42020221556.
FINDINGS
Our search identified 14 621 articles, of which 314 studies were included for analysis after screening, including 38 130 patients from 80 regions globally presenting during 1980-2020. 255 articles were entered for time-trend meta-analysis, covering 29 106 patients from 73 countries. Both overall survival (from 79% [95% CI 74-84] to 88% [83-93]; p=0·017) and globe salvage rate (from 22% [14-32] to 44% [36-52]; p=0·0003) improved significantly over the four decades. Wide disparities were observed between higher-income and lower-income countries. Overall survival, globe salvage, and globe salvage for advanced intraocular disease correlated positively with income level. Higher overall survival was associated with lower Gini index (p=0·0001) and with populations that had smaller percentages living in rural areas (p=0·0005). Higher globe salvage was associated with better health-care financing and accessibility (p=0·030). Overall survival (p=0·0024) and globe salvage (p=0·022) were both associated positively with education level. Survival gaps were observed in sub-Saharan Africa and southeast and southwest Asia.
INTERPRETATION
Retinoblastoma treatment outcomes have improved globally over the past four decades but large disparities persist between higher-income and lower-income countries, with some areas having major survival gaps. Targeted health-care policy making with increased health-care financing and accessibility are needed in low-income and lower-middle-income countries to improve retinoblastoma outcomes worldwide.
FUNDING
Health and Medical Research Fund (Hong Kong) and Children Cancer's Foundation (Hong Kong).
Topics: Global Health; Health Care Surveys; Humans; Organ Sparing Treatments; Retinoblastoma; Socioeconomic Factors
PubMed: 35093202
DOI: 10.1016/S2214-109X(21)00555-6 -
Journal of Clinical Laboratory Analysis Oct 2021Retinoblastoma is the most common primary intraocular malignancy in children less than 4 years. Retinoblastoma (RB) contains about 3%-5% of all childhood cancers....
BACKGROUND
Retinoblastoma is the most common primary intraocular malignancy in children less than 4 years. Retinoblastoma (RB) contains about 3%-5% of all childhood cancers. Recent studies demonstrated that interacting between RB tumor suppressor and oncoproteins of DNA tumor viruses such as human papillomavirus (HPV). The objective of the current systematic review study was to present conducted studies in the field of HPV infection and its possible role in retinoblastoma.
METHODS
For this systematic review, all relevant original research studies were assessed by searching in electronic databases include PubMed, Embase, Scopus, Google Scholar, and Web of Science by using relevant keywords. The study was designed based on the PRISMA criteria. All publications with English literature and original researches are considered for screening.
RESULTS
Conducted search results lead to 4070 studies. The title and abstract screening lead to 11 studies. Data extraction was performed on 8 included studies. The prevalence of the HPV was ranged from 0 to 69%, and HPV genotype 16 and 18 were the most detected types. The most used method for the detection of the viruses was PCR, and the most assessed sample was formalin-fixed, paraffin-embedded tissue blocks.
CONCLUSION
The association between HPV and retinoblastoma is still inconsistent. The prevalence of the HPV in RB was ranged from 0 to 69%, which indicates a wide range and highlights the importance of further investigation for more accurate statistical of HPV prevalence in RB. Thus, further worldwide studies of larger sample sizes of cohorts should be investigated to clarify this uncertainty.
Topics: Human papillomavirus 16; Human papillomavirus 18; Humans; Papillomavirus Infections; Prevalence; Retinal Neoplasms; Retinoblastoma
PubMed: 34462972
DOI: 10.1002/jcla.23981 -
Ocular Oncology and Pathology Mar 2021The published data on ocular survival following intravenous chemotherapy of retinoblastoma (RB) seems to be skewed by evolving practice patterns induced by use of... (Review)
Review
PURPOSE
The published data on ocular survival following intravenous chemotherapy of retinoblastoma (RB) seems to be skewed by evolving practice patterns induced by use of intravitreal chemotherapy (iVitc). We aimed to explore potential role of iVitc for vitreous seeding for patients treated with intravenous chemotherapy (IVC).
METHODS
A literature search was performed to identify cases of RB treated with primary IVC prior to advent of iVitc by various search engines (PubMed, Medline, and Google) from 1992 to 2018. Studies were excluded if number of cases were less than 40 or lacked data related to type of recurrence and its treatment. Rates and patterns of recurrence and its management were categorized.
RESULTS
Out of 15 studies identified, only 10 studies (797 eyes) met the inclusion criteria. The mean age at presentation was 15.3 months (range 0-192.8 months). Unilateral cases represented 25% of the cohort. The ocular survival rate with primary IVC was 63% (500/797 eyes). Of the 297 eyes (37%) that failed IVC therapy, additional 99 eyes could be salvaged with EBRT (599/797 eyes, 75%). Remaining 198 eyes were enucleated (198/797 eyes 25%). K-M survival analysis could not be done due lack of sufficient data. Recurrences that occurred (mean 12.2 months) after completion of primary IVC included relapse of retinal tumor (143 eyes [48%]), vitreous seeding (73 eyes [25%]), subretinal seeding (49 eyes [16%]), or any combination (103 eyes [35%]). Out of 73 eyes with vitreous seeding, additional 66 eyes (90%) would have been salvaged with iVitc, potentially improving ocular survival rates to 71% (500 + 66/797).
CONCLUSIONS
Evolving practice patterns of RB treatment have unfavorably skewed published ocular survival rates following IVC. With incorporation of iVitc, the ocular survival rates with IVC can be potentially improved to be non-inferior to those achieved with intra-arterial chemotherapy.
PubMed: 33981697
DOI: 10.1159/000510506 -
Cancers Apr 2021The aim of this systematic review is to assess the latest age at diagnosis for detection of familial retinoblastoma in order to evaluate at what age screening of at-risk...
The aim of this systematic review is to assess the latest age at diagnosis for detection of familial retinoblastoma in order to evaluate at what age screening of at-risk children could be discontinued. Extended screening beyond this age would result in unnecessary patient burden and costs. However, discontinuing screening prematurely would have the adverse effect of missing tumors. We performed a literature search (PubMed, Embase, CINAHL and the Cochrane Library) up until February of 2021 and systematically included studies where patients had a family history of retinoblastoma, a known age at diagnosis, and who were ophthalmologically screened for retinoblastoma from birth. A total of 176 familial retinoblastoma patients from 17 studies were included in this review. Based on 48 months of age being the latest age of diagnosis, ophthalmological screening for familial retinoblastoma could safely be discontinued at age four years.
PubMed: 33920538
DOI: 10.3390/cancers13081942 -
Asia-Pacific Journal of Ophthalmology...The aim of this study was to review the literature on various screening programs, devices, and applications described for the early detection of retinoblastoma.
PURPOSE
The aim of this study was to review the literature on various screening programs, devices, and applications described for the early detection of retinoblastoma.
DESIGN
Systematic review article.
METHODS
A PubMed® search was performed to identify articles published with specific reference to screening of neonates, infants and children for retinoblastoma.
RESULTS
Various devices and mobile phone-based applications based on altered red reflex are finding their way into community screening. Diagnosis of retinoblastoma by newborn eye screening is emphasized in several countries, and red reflex is the most widely employed technique.
CONCLUSIONS
Several screening programs for early detection of retinoblastoma are evolving in the developing countries, but the practices are not uniform. Universal newborn screening should be the norm. Newer tools and software can be utilized to screen infants on a community scale. Focussed research on revolutionizing digital imaging for a versatile screening tool holds promise for early diagnosis of retinoblastoma.
Topics: Child; Diagnostic Imaging; Early Diagnosis; Humans; Infant; Infant, Newborn; Neonatal Screening; Retinal Neoplasms; Retinoblastoma
PubMed: 33793441
DOI: 10.1097/APO.0000000000000378 -
Asia-Pacific Journal of Ophthalmology... Jan 2021To analyze the risk and benefit of high-dose chemotherapy followed by stem cell transplantation (HDCT-SCT) treatment in patients with advanced retinoblastoma.
PURPOSE
To analyze the risk and benefit of high-dose chemotherapy followed by stem cell transplantation (HDCT-SCT) treatment in patients with advanced retinoblastoma.
DESIGN
Systematic review.
METHODS
A comprehensive literature search from 4 online databases, including PubMed, Scopus, EBSCO, and Cochrane was done for original studies evaluating the use of HDCT followed by SCT in the treatment of patients with advanced retinoblastoma. The last search was performed on April 15, 2020.
RESULTS
A total of 35 studies consisting of 160 patients were considered suitable for inclusion. After HDCT-SCT treatment, 108/160 (67.5%) patients were alive with no evidence of disease at the last follow-up. The incidence of secondary malignancy in our data was also relatively low, which was 16/160 (10%) patients. The side effects were mainly hematological and gastrointestinal toxicities. The prognosis for metastatic cases especially the one to the central nervous system (CNS) remains poor, as shown in our data that 22 of 44 (50%) patients died due to the evidence of disease, and 12 of 44 (27%) patients acquired CNS relapse and died.
CONCLUSIONS
HDCT-SCT is a promising treatment option in patients with advanced retinoblastoma. The use of HDCT-SCT in CNS metastases needs to be carefully considered, possibly by adding thiotepa or topotecan to improve tumor control. Further randomized clinical trials are needed to draw firm conclusion regarding its safety and efficacy.
Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Humans; Neoplasm Recurrence, Local; Retinal Neoplasms; Retinoblastoma; Stem Cell Transplantation
PubMed: 33481395
DOI: 10.1097/APO.0000000000000372 -
Cancer Cell International 2020Retinoblastoma is the most common malignant rare intraocular tumor of childhood. Long noncoding RNAs (lncRNAs) have been reported participating in its progression, but... (Review)
Review
BACKGROUND
Retinoblastoma is the most common malignant rare intraocular tumor of childhood. Long noncoding RNAs (lncRNAs) have been reported participating in its progression, but their significance remains inconclusive. We conducted this systematic review and meta-analysis to explore specific lncRNA biomarker in patients with retinoblastoma.
MATERIALS AND METHODS
Eligible articles were searched from the Pubmed, Web of Science, Embase and the Cochrane library. Hazard ratios (HRs) and odds ratios (ORs) were extracted or calculated to evaluate the relationship between lncRNAs and retinoblastoma. The meta-analysis part was conducted with STATA v.15 software.
RESULTS
A total of 9 articles with 834 retinoblastoma patients are yielded. Heterogeneity among HRs of overall survival (OS) is notably high (I = 91.3%, p < 0.001). Subgroup analysis suggests that elevated expression of lncRNA BDNF-AS and MT1JP are favorable factors in OS (pooled HR = 1.89, 95% CI 1.72-2.07, I = 0%). Six articles included optic nerve invasion as a clinicopathological outcome and showed a notable correlation (pooled HR = 2.38, 95% CI 1.26-3.50, I = 0.0%). We validate our analysis via the public dataset and also sum up the studies of lncRNA BDNF-AS and MT1JP in other cancers.
CONCLUSION
Differential expression of lncRNAs has been reported in retinoblastoma. Some of them showed potential in retinoblastoma prognosis and progression.
PubMed: 32514246
DOI: 10.1186/s12935-020-01281-0