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Cancers Nov 2022: Posterior fossa tumors (PFTs) are a morbid group of central nervous system tumors that most often present in childhood. While early diagnosis is critical to drive... (Review)
Review
: Posterior fossa tumors (PFTs) are a morbid group of central nervous system tumors that most often present in childhood. While early diagnosis is critical to drive appropriate treatment, definitive diagnosis is currently only achievable through invasive tissue collection and histopathological analyses. Machine learning has been investigated as an alternative means of diagnosis. In this systematic review and meta-analysis, we evaluated the primary literature to identify all machine learning algorithms developed to classify and diagnose pediatric PFTs using imaging or molecular data. : Of the 433 primary papers identified in PubMed, EMBASE, and Web of Science, 25 ultimately met the inclusion criteria. The included papers were extracted for algorithm architecture, study parameters, performance, strengths, and limitations. : The algorithms exhibited variable performance based on sample size, classifier(s) used, and individual tumor types being investigated. Ependymoma, medulloblastoma, and pilocytic astrocytoma were the most studied tumors with algorithm accuracies ranging from 37.5% to 94.5%. A minority of studies compared the developed algorithm to a trained neuroradiologist, with three imaging-based algorithms yielding superior performance. Common algorithm and study limitations included small sample sizes, uneven representation of individual tumor types, inconsistent performance reporting, and a lack of application in the clinical environment. : Artificial intelligence has the potential to improve the speed and accuracy of diagnosis in this field if the right algorithm is applied to the right scenario. Work is needed to standardize outcome reporting and facilitate additional trials to allow for clinical uptake.
PubMed: 36428701
DOI: 10.3390/cancers14225608 -
Frontiers in Surgery 2022Survival amongst posterior fossa tumour (PFT) patients is improving. Clinical endpoints such as overall survival fail to depict QoL. There is yet to be a review of... (Review)
Review
INTRODUCTION
Survival amongst posterior fossa tumour (PFT) patients is improving. Clinical endpoints such as overall survival fail to depict QoL. There is yet to be a review of current QoL instruments used for adult PFTs. Aim of this review is to outline the QoL reporting in the management of PFTs and measure participation level.
METHODS
This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis. A search strategy to identify adult patients with PFTs who took part in QoL metrics was conducted. Observational and experimental studies published from 1990 to date were included. Studies with a sample size less than 10 and performance measures such as Karnofsky Performance Status were not considered.
RESULTS
A total of 116 studies were included in the final analysis. Vestibular schwannomas were the most common tumour pathology ( = 23,886, 92.6%) followed by pilocytic astrocytomas ( = 657, 2.5%) and meningiomas ( = 437, 1.7%) Twenty-five different QoL measures were used in the study pool. SF-36 was the most common ( = 55, 17 47.4%) QoL metric in the whole study pool, followed by the Penn Acoustic Neuroma QoL scale ( = 24, 20.7%) and Dizziness Handicap Inventory ( = 16, 13.8%). Seventy-two studies reported less-than 100% participation in QoL evaluation. The commonest reason for non-participation was a lack of response ( = 1,718, 60.8%), incomplete questionnaires ( = 268, 9.4%) and cognitive dysfunction ( = 258, 9.1%).
CONCLUSION
Informed clinical decision-making in PFT patients requires the development of specific QoL outcomes. Core outcome sets, and minimal clinically important differences (MCID) are essential for these metrics to show clinically significant improvements in patient QoL.
PubMed: 36303860
DOI: 10.3389/fsurg.2022.970889 -
Brain & Spine 2022Pediatric Brain Tumors (PBT) are a common cause of cancer-related mortality globally. Contrary to high-income countries (HIC), survival rates in low-and-middle income... (Review)
Review
BACKGROUND
Pediatric Brain Tumors (PBT) are a common cause of cancer-related mortality globally. Contrary to high-income countries (HIC), survival rates in low-and-middle income countries (LMIC) remains low despite advances in neurosurgical care and diagnostics over the past decades. The aim of this systematic review was to investigate the surgical outcomes for PBT in Sub-Saharan Africa, and the distribution of PBT types.
METHODS
A systematic review was conducted on PubMed, for all available literature on the surgical outcomes of PBT in Sub-Saharan Africa, published before May 3, 2022. Two reviewers performed abstract, full text screening and data collection independently, resolving any conflicts by consensus.
RESULTS
The search yielded 256 studies, of which 22 met the inclusion criteria, amounting to a total of 243 patients. Nigeria was the country with most data. Only subgroups of patients could be extracted from 12 studies, and variables of interest in 6 studies had inconsistent sample sizes. The age centered around 9 years, and there were approximately equal number of girls and boys. The most common tumor was medulloblastoma, followed by craniopharyngioma and astrocytoma. There was large heterogeneity in the reporting of outcomes, and a trend was difficult to discern, considering the large number of different tumor types and different extents of resection.
DISCUSSION AND CONCLUSION
Data is insufficient and inconsistent, precluding statistical conclusions. There is a need for more studies in the field.
PubMed: 36248098
DOI: 10.1016/j.bas.2022.100912 -
Cancers May 2022Pediatric brain tumors are the most common solid tumor in children. Traditionally, tumor diagnosis and molecular analysis were carried out on tumor tissue harvested... (Review)
Review
BACKGROUND
Pediatric brain tumors are the most common solid tumor in children. Traditionally, tumor diagnosis and molecular analysis were carried out on tumor tissue harvested either via biopsy or resection. However, liquid biopsy allows analysis of circulating tumor DNA in corporeal fluids such as cerebrospinal fluid or blood.
METHODS
We performed a systematic review in Pubmed and Embase regarding the role of liquid biopsy in pediatric brain tumors.
RESULTS
Nine studies with a total of 570 patients were included. The preferred corporeal fluid for analysis with a relatively high yield of ct-DNA was cerebrospinal fluid (CSF). For high-grade glioma, liquid biopsy can successfully characterize H3K27mutations and predict tumor progression before it is radiographically detected. Moreover, liquid biopsy has the potential to distinguish between pseudo-progression and actual progression. In medulloblastoma, ct-DNA in the CSF can be used as a surrogate marker of measurable residual disease and correlates with response to therapy and progression of the tumor up to three months before radiographic detection.
CONCLUSION
Liquid biopsy is primarily useful in high-grade pediatric brain tumors such as diffuse midline glioma or medulloblastoma. Disease detection and monitoring is feasible for both tumor entities. More trials to standardize its use for pediatric brain tumors are necessary.
PubMed: 35681663
DOI: 10.3390/cancers14112683 -
Neuro-oncology Advances 2022Medulloblastoma is a rare diagnosis among adolescents and young adults (AYA). Though prognostic factors and treatment are well characterized among children with... (Review)
Review
BACKGROUND
Medulloblastoma is a rare diagnosis among adolescents and young adults (AYA). Though prognostic factors and treatment are well characterized among children with medulloblastoma, equivalent data for AYA are sparse. We conducted a systematic review to identify predictors of survival among AYA with medulloblastoma.
METHODS
We searched for primary studies of AYA (age 15-39 at diagnosis) with medulloblastoma in high-income countries within OVID MEDLINE, EMBASE, and EBM Reviews-Cochrane library databases from inception to August 2020. Patient demographics, primary outcomes, and univariate and multivariable data on all prognostic factors were collected from included studies. Prognosticators were characterized as patient, disease, or treatment-related.
RESULTS
We identified 18 articles. 5-year overall survival ranged between 40% and 89%, while disease-free survival ranged from 49% to 89%. Study quality was low as assessed by the Quality in Prognostic factor Studies tool. Though meta-analyses were not possible due heterogeneity, narrative summaries suggested that lower disease burden, superior postoperative functional status, and higher doses and larger fields of radiation were associated with improved survival. Reported chemotherapy regimens were heterogeneous in timing, agents, and relationship with radiation, precluding meaningful comparisons. Only one study included molecular subgroups for analysis, with the majority (76.5%) of tumors classified as Sonic Hedgehog (SHH).
CONCLUSIONS
Prognostication and treatment of AYA medulloblastoma is limited by a dearth of primary evidence and lack of specificity for patients aged 15-39. Dedicated prospective trials to delineate the benefit of various chemotherapy and radiation regimens are required in this population to identify prognosticators and ideal treatment regimens.
PubMed: 35669013
DOI: 10.1093/noajnl/vdac016 -
Frontiers in Oncology 2022Conventional parameters show limited and unreliable correlations with medulloblastoma prognosis.
BACKGROUND
Conventional parameters show limited and unreliable correlations with medulloblastoma prognosis.
AIM
To evaluate the factors influencing overall survival (OS), event-free survival (EFS), and progression-free survival (PFS) in patients with medulloblastoma.
METHODS
PubMed, EMBASE, the Cochrane Library, and Web of Science were searched for studies published up to May 2021. The associations between various clinical and treatment factors and survival parameters were assessed.
RESULTS
Twenty-nine studies (8455 patients) were included. Desmoplastic medulloblastoma (HR=0.41, 95%CI: 0.31-0.56), M0 disease (HR=2.07, 95%CI: 1.48-2.89), WNT, SSH, group 4 (all P<0.05 vs. group 3), GTR vs. STR (HR=1.37, 95%CI: 1.04-1.08), radiotherapy (HR=0.45, 95%CI: 0.20-0.80), craniospinal irradiation (HR=0.49, 95%CI: 0.38-0.64), and high 5hmC levels (HR=2.90, 95%CI: 1.85-4.55) were associated with a better OS. WNT, SSH, group 4 (all P<0.05 vs. group 3), residual tumor ≤1.5 cm (HR=2.08, 95%CI: 1.18-3.68), GTR vs. STR (HR=1.31, 95%CI: 1.03-1.68), craniospinal irradiation (HR=0.46, 95%CI: 0.37-0.57), high 5hmC levels (HR=3.10, 95%CI: 2.01-4.76), and <49 days between resection and radiotherapy (HR=2.54, 95%CI: 1.48-4.37) were associated with better PFS. Classic vs. desmoplastic medulloblastoma (HR=1.81, 95%CI: 1.04-3.16), SSH, WNT (both P<0.05 vs, non-SSH/non-WNT), GTR vs. STR (HR=2.01, 95%CI: 1.42-2.85), and radiotherapy (HR=0.31, 95%CI: 0.15-0.64) were associated with a better EFS.
CONCLUSION
Histology, molecular subgroup, GTR, and radiotherapy are significantly associated with survival parameters in patients with medulloblastoma. Nevertheless, high-quality prospective cohort studies are necessary to improve the conclusions.
PubMed: 35311074
DOI: 10.3389/fonc.2022.827054 -
International Journal of Molecular... Dec 2021Medulloblastoma is a common fatal pediatric brain tumor. More treatment options are required to prolong survival and decrease disability. mTOR proteins play an essential... (Review)
Review
Medulloblastoma is a common fatal pediatric brain tumor. More treatment options are required to prolong survival and decrease disability. mTOR proteins play an essential role in the disease pathogenesis, and are an essential target for therapy. Three generations of mTOR inhibitors have been developed and are clinically used for immunosuppression and chemotherapy for multiple cancers. Only a few mTOR inhibitors have been investigated for the treatment of medulloblastoma and other pediatric tumors. The first-generation mTOR, sirolimus, temsirolimus, and everolimus, went through phase I clinical trials. The second-generation mTOR, AZD8055 and sapanisertib, suppressed medulloblastoma cell growth; however, limited studies have investigated possible resistance pathways. No clinical trials have been found to treat medulloblastoma using third-generation mTOR inhibitors. This systematic review highlights the mechanisms of resistance of mTOR inhibitors in medulloblastoma and includes IDO1, T cells, Mnk2, and eIF4E, as they prolong malignant cell survival. The findings promote the importance of combination therapy in medulloblastoma due to its highly resistant nature.
Topics: Antineoplastic Agents; Child; Drug Resistance, Neoplasm; Humans; Medulloblastoma; Protein Kinase Inhibitors; TOR Serine-Threonine Kinases
PubMed: 35008889
DOI: 10.3390/ijms23010464 -
Ontario Health Technology Assessment... 2021Proton beam therapy has potential to reduce late toxicity in cancer treatment by reducing the risk of damage to surrounding healthy tissues. We conducted a health...
BACKGROUND
Proton beam therapy has potential to reduce late toxicity in cancer treatment by reducing the risk of damage to surrounding healthy tissues. We conducted a health technology assessment of proton beam therapy, compared with photon therapy, for children and adults with cancer requiring radiotherapy. Our assessment included an evaluation of safety, effectiveness, cost-effectiveness, the budget impact of publicly funding the construction and use of proton beam therapy in Ontario, and patient preferences and values.
METHODS
We performed a systematic literature search of the clinical evidence to retrieve systematic reviews and selected and reported results from one review that was recent, high quality, and relevant to our research question. We complemented the chosen systematic review (published in 2019) with a literature search to identify randomized controlled trials published after the review. We assessed the risk of bias of each included study using the Risk of Bias in Systematic Reviews (ROBIS) tool and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search and also analyzed the budget impact of publicly funding proton beam therapy in cancer patients in Ontario. To contextualize the potential value of proton beam therapy, we spoke with 10 people with cancer (or their caregivers) who had either received or were considering proton beam therapy.
RESULTS
We included one systematic review of the clinical evidence reporting on 215 publications on proton beam therapy in children and adults across 19 tumour categories/conditions. Compared with photon therapy, proton beam therapy may result in fewer adverse events but similar overall survival and progression-free survival in children with brain tumours (GRADE: Low), adults with esophageal cancer (GRADE: Low to Very low), head and neck cancer (GRADE: Low to Very low), and prostate cancer (GRADE: Low). Proton beam therapy may result in similar adverse events, overall survival, and progression-free survival in adults with brain tumours (GRADE: Low), breast cancer (GRADE: Low), gastrointestinal cancer (GRADE: Very low), liver cancer (GRADE: Moderate to Very low), lung cancer (GRADE: Moderate to Very low), and ocular tumours (GRADE: Low). There was insufficient evidence to evaluate the effectiveness and safety of proton beam therapy in other pediatric tumours, as well as bladder cancer, bone cancer, lymphoma, and benign tumours in adults.The economic evidence suggests that proton beam therapy may be cost-effective in pediatric populations with medulloblastoma; however, studies were based on limited clinical evidence. In other indications, the cost-effectiveness of proton beam therapy is unclear. The 5-year budget impact of funding a four-room proton beam therapy centre in Ontario would be $124.8 million, resulting in a cost per patient of $48,217, including both capital investment and operational costs, compared to the current average cost of $326,800 to send patients out of country. Funding a one-room proton beam therapy centre that would treat selected Ontario patients and patients from other Canadian provinces would have a lower budget impact of $15.2 million over the next 5 years. If we assume building proton beam therapy centres would substitute for new photon therapy centres, then the 5-year budget impact could be further reduced to approximately $13 million (one room) or $94.8 million (four rooms). The people we interviewed who had received proton beam therapy reported positive responses to the treatment. They chose to have proton beam therapy because they believed it to be safer and to have fewer long-term side effects than photon therapy. However, accessing proton beam therapy in the United States was often challenging, with logistical and emotional burdens. Patients and families valued the opportunity to receive effective treatment close to family and other emotional supports.
CONCLUSIONS
Proton beam therapy may be as effective as conventional radiation therapy, and it may cause fewer side effects, especially for children with brain tumours and for adults with certain types of cancer. Based on published economic evidence, proton beam therapy is likely cost-effective compared with photon therapy in children with medulloblastoma, but cost-effectiveness is unclear in children and adults with other clinical indications. We estimate that publicly funding a proton beam therapy centre in Ontario would result in additional costs of $124.8 million over the next 5 years, but with a six- to seven-fold reduction in the per-patient cost compared with current spending. People with cancer and caregivers with whom we spoke were generally supportive of having proton beam therapy available in Ontario.
Topics: Adult; Child; Cost-Benefit Analysis; Female; Humans; Male; Neoplasms; Ontario; Proton Therapy; Technology Assessment, Biomedical
PubMed: 34055109
DOI: No ID Found -
Cancer Reports (Hoboken, N.J.) Jun 2022The Leila Rose Foundation ("the Foundation") was established in April 2011, to address financial toxicity as well as the gaps in knowledge and support for families...
BACKGROUND
The Leila Rose Foundation ("the Foundation") was established in April 2011, to address financial toxicity as well as the gaps in knowledge and support for families affected by a rare childhood cancer diagnosis in Australia.
AIM
The aim of this brief report is to analyze the diagnostic trends surrounding the rare cancer diagnoses for patients referred to the Foundation over the past decade and to present case studies evaluating the role of the Foundation's Family Support Coordinator in providing tailored, individualized support for families.
METHODS
Eligibility for family support is restricted to children ≤ 14 years of age at diagnosis with a cancer that has an incidence less than 5% of all childhood cancers in Australia as reflected by national registry data. The analysis of diagnostic trends in this report, was based upon a systematic review of enrolment records. The role of the Family Support Coordinator is presented in four different case studies.
RESULTS
As at 1 November 2020, the Foundation has supported 197 families affected by rare childhood cancer. Financial support of $825,000 has been provided directly to these families. Enrollment records demonstrate that 35 patients representing 18% of all enrollments have had a unique diagnosis that has not been recorded for any other enrolled patient highlighting that these diagnoses are very rare. The most frequent diagnoses have included Medulloblastoma, Ewing's Sarcoma and Wilm's Tumor (20, 19, 19 patients respectively). The Family Support Coordinator role has provided individualized support for families which has been greatly appreciated based upon ad hoc family feedback.
CONCLUSIONS
Challenges remain in terms of improving outcomes for families affected by rare childhood cancer. The Foundation is committed to leaving no stone unturned and delivering its unique support services to families in order to reduce the burden caused by a rare childhood cancer diagnosis both now and in the future.
Topics: Australia; Child; Humans; Incidence; Neoplasms; Registries
PubMed: 33939318
DOI: 10.1002/cnr2.1381 -
Neurosurgical Review Feb 2021The cerebellum is historically implicated in motor coordination, but accumulating modern evidence indicates involvement in non-motor domains, including cognition,...
The cerebellum is historically implicated in motor coordination, but accumulating modern evidence indicates involvement in non-motor domains, including cognition, emotion, and language. This correlates with the symptoms observed in postoperative cerebellar mutism syndrome (CMS). Profound knowledge of cerebellar functional topography and tractography is important when approaching cerebellar tumors, as surgical trauma to relevant structures of cerebellar pathways plays a role in the pathogenesis of CMS. The aim of this systematic review is to provide a concise overview of relevant modern neuroimaging data and cerebellar functional tracts with regard to neurosurgical procedures.
Topics: Cerebellum; Humans; Neural Pathways; Neuroimaging; Neurosurgeons; Neurosurgical Procedures
PubMed: 32056026
DOI: 10.1007/s10143-020-01242-1