Objective: To date, the understanding of pediatric tumor genomics and how these genetic aberrations correlate with clinical outcome is lacking. Here, we report our experience with the next-generation sequencing (NGS) test program and discuss implications for the inclusion of molecular profiling into clinical pediatric oncology trials. We also aimed to explore studies on NGS in pediatric cancers and to quantify the variability of finding actionable mutations and the clinical implications.
Methods: We present a retrospective case series of all patients whose tumor tissue underwent NGS tests during treatment in our department. We also reviewed the literature and carried out a meta-analysis to explore studies on NGS in pediatric cancers.
Results: In 35/37 (94%) patients, we found at least one genomic alteration (GA); mean number of GAs per patient was 2 (range, 0–67), while 164 GAs were detected. Only 3 (8%) patients received precision medicine due to their GAs for a mean of 9 months (range, 5–14 months). Four studies were included in the meta-analysis. The pooled positive actionable mutation rate was 52% (95% CI 39%–66%), and the pooled rate of children who received precision medicine was 10% (95% CI 3%–20%).
Conclusions: In children and young adults with high-risk, recurrent, or refractory malignancies, tumor profiling results have clinical implications, despite barriers to the use of matched precision therapy.
TO THE EDITOR
We read with interest the report by Yeshayahu about four minors who were diagnosed late with non-COVID-19 diseases during the COVID-19 pandemic (Rambam Maimonides Med J 2021;12:e0017. doi: 10.5041/RMMJ.10431 ). We would like to emphasize that, firstly, such delays are not limited to minors, and secondly, that also in minors should we distinguish the administrative and the physiological meanings of the term “child” and hence distinguish administratively defined “chil¬dren” who bodily are already mature from those young patients who bodily are indeed still children.
TO THE EDITOR
I read with interest the letter by Klaus Rose et al. regarding the article about delayed diagnosis of severe medical conditions during the coronavirus disease 2019 (COVID-19) pandemic.1 The author stressed the importance of recognizing that delayed presentation of patients, during the COVID-19 pandemic, was not limited to the pediatric population. I agree with this important point, and the article does not claim otherwise. The presented cases are pediatric, given that they took place in a pediatric department, but it is reasonable to assume that adults have faced the same challenges.
To the Editor:
I have followed, with great interest, the passionate debate held between Lichtman, and Ashkenazi and Olsha in Rambam Maimonides Medical Journal. Lichtman put forward a curious and enlightening proposal to offer a fractional value to each author, depending on the value of their relative contribution, with the total amounting to 1, as a way to reduce authorship abuses, such as gift or guest authorship, which are two very prevalent forms of authorship abuses in academic publishing today.
Objective: Medical decision-making is often uncertain. The positive predictive value (PPV) and negative predictive value (NPV) are conditional probabilities characterizing diagnostic tests and assessing diagnostic interventions in clinical medicine and epidemiology. The PPV is the probability that a patient has a specified disease, given a positive test result for that disease. The NPV is the probability that a patient does not have the disease, given a negative test result for that disease. Both values depend on disease incidence or prevalence, which may be highly uncertain for unfamiliar diseases, epidemics, etc. Probability distributions for this uncertainty are usually unavailable. We develop a non-probabilistic method for interpreting PPV and NPV with uncertain prevalence.
Methods: Uncertainty in PPV and NPV is managed with the non-probabilistic concept of robustness in info-gap theory. Robustness of PPV or NPV estimates is the greatest uncertainty (in prevalence) at which the estimate’s error is acceptable.
Results: Four properties are demonstrated. Zeroing: best estimates of PPV or NPV have no robustness to uncertain prevalence; best estimates are unreliable for interpreting diagnostic tests. Trade-off: robustness increases as error increases; this trade-off identifies robustly reliable error in PPV or NPV. Preference reversal: sometimes sub-optimal PPV or NPV estimates are more robust to uncertain incidence or prevalence than optimal estimates, motivating reversal of preference from the putative optimum to the sub-optimal estimate. Trade-off between specificity and robustness to uncertainty: the robustness increases as test-specificity decreases. These four properties underlie the interpretation of PPV and NPV.
Conclusions: The PPV and NPV assess diagnostic tests, but are sensitive to lack of knowledge that generates non-probabilistic uncertain prevalence and must be supplemented with robustness analysis. When uncertainties abound, as with unfamiliar diseases, assessing robustness is critical to avoiding erroneous decisions.
The outbreak of coronavirus disease 2019 (COVID-19) in Italy, the first Western country hit by the pandemic, seriously impacted the Italian healthcare system and social and economic environment. This perspective piece focuses on the main challenges faced by Italian hospital managements: hospital overcrowding; the need for urgent reorganization of the country’s healthcare systems; the lack of data regarding COVID-19 diagnostics, clinical course, and effective treatment; individual and collective consequences of the crisis; and the importance of disease containment measures and early treatment strategies.
