Neurocognitive outcomes in pediatric brain tumors after treatment with proton versus photon radiation: a systematic review and meta-analysis.

BACKGROUND: Advances in cancer treatments, particularly the development of radiation therapy, have led to improvements in survival outcomes in children with brain tumors. However, radiation therapy is associated with significant long-term neurocognitive morbidity. The present systematic review and meta-analysis aimed to compare the neurocognitive outcomes of children and adolescents with brain tumors treated with photon radiation (XRT) or proton therapy (PBRT). METHODS: A systematic search was conducted (PubMed, Embase, Cochrane, and Web of Science from inception until 02/01/2022) for studies comparing the neurocognitive outcomes of children and adolescents with brain tumors treated with XRT vs. PBRT. The pooled mean differences (expressed as Z scores) were calculated using a random effects method for those endpoints analyzed by a minimum of three studies. RESULTS: Totally 10 studies (n = 630 patients, average age range: 1-20 years) met the inclusion criteria. Patients who had received PBRT achieved significantly higher scores (difference in Z scores ranging from 0.29-0.75, all P < 0.05 and significant in sensitivity analyses) after treatment than those who had received XRT for most analyzed neurocognitive outcomes (i.e., intelligence quotient, verbal comprehension and perceptual reasoning indices, visual motor integration, and verbal memory). No robust significant differences (P > 0.05 in main analyses or sensitivity analyses) were found for nonverbal memory, verbal working memory and working memory index, processing speed index, or focused attention. CONCLUSIONS: Pediatric brain tumor patients who receive PBRT achieve significantly higher scores on most neurocognitive outcomes than those who receive XRT. Larger studies with long-term follow-ups are needed to confirm these results.

Identification of germline cancer predisposition variants in pediatric sarcoma patients from somatic tumor testing.

Genetic predisposition is an important risk factor for cancer in children and adolescents but detailed associations of individual genetic mutations to childhood cancer are still under intense investigation. Among pediatric cancers, sarcomas can arise in the setting of cancer predisposition syndromes. The association of sarcomas with these syndromes is often missed, due to the rarity and heterogeneity of sarcomas and the limited search of cancer genetic syndromes. This study included 43 pediatric and young adult patients with different sarcoma subtypes. Tumor profiling was undertaken using the Oncomine Childhood Cancer Research Assay (Thermo Fisher Scientific). Sequencing results were reviewed for potential germline alterations in clinically relevant genes associated with cancer predisposition syndromes. Jongmans´ criteria were taken into consideration for the patient selection. Fifteen patients were selected as having potential pathogenic germline variants due to tumor sequencing that identified variants in the following genes: CDKN2A, NF1, NF2, RB1, SMARCA4, SMARCB1 and TP53. The variants found in NF1 and CDKN2A in two different patients were detected in the germline, confirming the diagnosis of a cancer predisposition syndrome. We have shown that the results of somatic testing can be used to identify those at risk of an underlying cancer predisposition syndrome.

Hospital-based proton therapy implementation during the COVID pandemic: early clinical and research experience in a European academic institution.

INTRODUCTION: A rapid deploy of unexpected early impact of the COVID pandemic in Spain was described in 2020. Oncology practice was revised to facilitate decision-making regarding multimodal therapy for prevalent cancer types amenable to multidisciplinary treatment in which the radiotherapy component searched more efficient options in the setting of the COVID-19 pandemic, minimizing the risks to patients whilst aiming to guarantee cancer outcomes. METHODS: A novel Proton Beam Therapy (PBT), Unit activity was analyzed in the period of March 2020 to March 2021. Institutional urgent, strict and mandatory clinical care standards for early diagnosis and treatment of COVID-19 infection were stablished in the hospital following national health-authorities' recommendations. The temporary trends of patients care and research projects proposals were registered. RESULTS: 3 out of 14 members of the professional staff involved in the PBR intra-hospital process had a positive test for COVID infection. Also, 4 out of 100 patients had positive tests before initiating PBT, and 7 out of 100 developed positive tests along the weekly mandatory special checkup performed during PBT to all patients. An update of clinical performance at the PBT Unit at CUN Madrid in the initial 500 patients treated with PBT in the period from March 2020 to November 2022 registers a distribution of 131 (26%) pediatric patients, 63 (12%) head and neck cancer and central nervous system neoplasms and 123 (24%) re-irradiation indications. In November 2022, the activity reached a plateau in terms of patients under treatment and the impact of COVID pandemic became sporadic and controlled by minor medical actions. At present, the clinical data are consistent with an academic practice prospectively (NCT05151952). Research projects and scientific production was adapted to the pandemic evolution and its influence upon professional time availability. Seven research projects based in public funding were activated in this period and preliminary data on molecular imaging guided proton therapy in brain tumors and post-irradiation patterns of blood biomarkers are reported. CONCLUSIONS: Hospital-based PBT in European academic institutions was impacted by COVID-19 pandemic, although clinical and research activities were developed and sustained. In the post-pandemic era, the benefits of online learning will shape the future of proton therapy education.

Maintained effectiveness of an electronic alert system to prevent venous thromboembolism among hospitalized patients.

Despite current guidelines, venous thromboembolism (VTE) prophylaxis is underused. Computerized programs to encourage physicians to apply thromboprophylaxis have been shown to be effective in selected populations. Our aim was to analyze the impact of the implementation of a computer-alert system for VTE risk in all hospitalized patients of a teaching hospital. A computer program linked to the clinical record database was developed to assess all hospitalized patients' VTE risk daily. The physician responsible for patients at high risk was alerted, but remained free to order or withhold prophylaxis. Over 19,000 hospitalized, medical and surgical, adult patients between January to June 2005 (pre-intervention phase), January to June 2006 and January to June 2007 (post-intervention phase), were included. During the first semesters of 2006 and 2007, an electronic alert was sent to 32.8% and 32.2% of all hospitalized patients, respectively. Appropriate prophylaxis among alerted patients was ordered in 89.7% (2006) and 88.5% (2007) of surgical patients, and in 49.2% (2006) and 64.4% (2007) of medical patients. A sustained reduction of VTE during hospitalization was achieved, Odds ratio (OR): 0.53, 95% confidence interval (CI) (0.25-1.10) and OR: 0.51, 95%CI (0.24-1.05) during the first semesters of 2006 and 2007 respectively, the impact being significant (p < 0.05) among medical patients in 2007, OR: 0.36, 95%CI (0.12-0.98). The implementation of a computer-alert program helps physicians to assess each patient's thrombotic risk, leading to a better use of thromboprophylaxis, and a reduction in the incidence of VTE among hospitalized patients. For the first time, an intervention aimed to improve VTE prophylaxis shows maintained effectiveness over time.

Factors influencing the use of thromboprophylaxis in cancer outpatients in clinical practice: A prospective study.

INTRODUCTION: Current clinical practice guidelines do not recommend routine pharmacological thromboprophylaxis in cancer outpatients receiving chemotherapy. However, a high proportion of cancer-associated venous thromboembolism (VTE) events occur in this setting. There are scarce data on the use of thromboprophylaxis in ambulatory cancer patients in real clinical practice. MATERIAL AND METHODS: We conducted a single-center prospective study aimed to evaluate the use and factors influencing pharmacological prophylaxis in consecutive cancer patients receiving ambulatory chemotherapy. Patients were followed for 90 days after inclusion. RESULTS: A total of 1108 patients were included. According to the Khorana score, 45.8% patients were classified as low-risk, 47.4% intermediate-risk and 6.8% as high-risk. Outpatient pharmacological prophylaxis was administered at any time during follow-up to 157 patients (14.2%) with a median duration of 42 days (range 1-90). Main factors influencing thromboprophylaxis were: previous history of VTE (odds ratio [OR], 19.11; 95% CI, 9.61-37.98), intercurrent hospitalization (OR, 5.40; 95% CI, 3.57-8.16), and gastrointestinal or gynecologic cancer (OR, 1.76; 95% CI, 1.11-2.80 and OR, 2.34; 95% CI, 1.05-5.26, respectively). During follow-up 58 (5.2%) VTE events were observed. Independent predictors of VTE were the site of malignancy (OR, 3.04; 95%CI, 1.20-7.71 and OR, 2.47; 95%CI, 1.21-5.01 for pancreas and lung cancer, respectively) and previous VTE (OR, 4.23; 95%CI, 1.26-14.27). Outpatient prophylaxis was associated with a lower risk of VTE during follow-up (OR, 0.30; 95%CI, 0.10-0.95). CONCLUSIONS: Although the type of malignancy appears as the most relevant variable for decision-making, additional efforts are required to identify patients at particular high thrombosis risk.

High incidence of venous thromboembolism despite electronic alerts for thromboprophylaxis in hospitalised cancer patients.

Many cancer patients are at high risk of venous thromboembolism (VTE) during hospitalisation; nevertheless, thromboprophylaxis is frequently underused. Electronic alerts (e-alerts) have been associated with improvement in thromboprophylaxis use and a reduction of the incidence of VTE, both during hospitalisation and after discharge, particularly in the medical setting. However, there are no data regarding the benefit of this tool in cancer patients. Our aim was to evaluate the impact of a computer-alert system for VTE prevention in patients with cancer, particularly in those admitted to the Oncology/Haematology ward, comparing the results with the rest of inpatients at a university teaching hospital. The study included 32,167 adult patients hospitalised during the first semesters of years 2006 to 2010, 9,265 (28.8%) with an active malignancy. Appropriate prophylaxis in medical patients, significantly increased over time (from 40% in 2006 to 57% in 2010) and was maintained over 80% in surgical patients. However, while e-alerts were associated with a reduction of the incidence of VTE during hospitalisation in patients without cancer (odds ratio [OR] 0.31; 95% confidence interval [CI], 0.15-0.64), the impact was modest in cancer patients (OR 0.89; 95% CI, 0.42-1.86) and no benefit was observed in patients admitted to the Oncology/Haematology Departments (OR 1.11; 95% CI, 0.45-2.73). Interestingly, 60% of VTE episodes in cancer patients during recent years developed despite appropriate prophylaxis. Contrary to the impact on hospitalised patients without cancer, implementation of e-alerts for VTE risk did not prevent VTE effectively among those with malignancies.