Unlocking delays: revealing barriers to early diagnosis of childhood central nervous system tumors in an upper-middle-income country.

PURPOSE: Childhood central nervous system (CNS) tumors tend to have a longer time interval until diagnosis than other pediatric malignancies. The aim is to describe the time to diagnosis among Brazilian pediatric patients treated at a tertiary center and explore associated factors. METHODS: Cross-sectional study; application of questionnaires to parents of children with CNS tumors during outpatient visit or inpatient care. RESULTS: One hundred parents participated between August and November 2023. The median age of the children at diagnosis was 7.2 years old. Low-grade glioma (LGG) was the most common tumor type (37%), followed by medulloblastoma (24%). The most frequent symptoms were morning and/or persistent vomiting and headache. The mean prediagnostic symptomatic interval (PSI) was 150 days. The mean parental interval was shorter than the medical (58.1 days vs 92.8 days). LGGs and tumors located in the central area had longer intervals to diagnosis than other tumors (296 vs 54 days) (p = 0.005) and (206 vs 155 days) (p = 0.007), respectively. Despite 81% of the patients undergoing pediatric routine follow-up, 87% of them had been diagnosed at an emergency department. Children attended by the same physician had a shorter mean interval (18.2 vs 88.3 days) than those assisted by different professionals (p = 0.015). The mean time for referral to our specialized center was 23 days. CONCLUSIONS: This study is a crucial step in recognizing barriers to early diagnosis of CNS tumors in a middle-income country as low awareness of signs/symptoms by parents and health professionals, aiming to provide opportunities for intervention strategies to reduce the time to diagnosis.

The TeLeo Program: Tele-education in pediatric oncology as a tool to support training programs in Latin America.

The TeLeo Program offers a free-access 2-year online learning program to support fellowship programs in pediatric oncology, enhance networking opportunities, and facilitate the exchange of context-specific, educational content within the pediatric oncology community in training in Latin America. In its first edition beginning in 2021, 185 fellows from 40 centers in 12 Latin American countries were enrolled. Additional courses for other healthcare professionals related to oncology in the region were produced to further support the program. A digital platform was created to allow users to easily access learning activities after registration, with 7075 professionals currently registered.

International Society of Paediatric Oncology (SIOP) Global Mapping Program: Analysis of healthcare centers in countries of the Latin American Society of Pediatric Oncology (SLAOP).

BACKGROUND: The International Society of Paediatric Oncology Society Global Mapping Program aims to describe the local pediatric oncology capacities. Here, we report the data from Latin America. METHODS: A 10-question survey was distributed among chairs of pediatric oncology services. Centers were classified according to patient volume into high- (HVC; 100 or more new cases per year), medium- (MVC; 31-99 cases), and low-volume centers (LVC; 30 cases or less), respectively. National referral centers (NRC) were identified. RESULTS: Total 307 centers in 20 countries were identified (271 responded), and 264 responses were evaluable, accounting for 78% of the expected cases (21,359 cases per year). Seventy-seven percent of patients are treated in public centers, including additional support by civil society organizations. We found that 66% of the patients are treated in 70 centers of excellence, including 21 NRC. There was a median of one pediatric oncologist every 21 newly diagnosed patients (44 for NRC), and in 84% of the centers, nurses rotated to other services. A palliative care team was lacking in 25% of the centers. LVC with public funding have significantly lower probability of having a palliative care team or trained pediatric oncology surgeons. Psychosocial, pharmacy, and nutrition services were available in more than 93% of the centers. No radiotherapy facility was available on campus in nine of 21 NRC. CONCLUSIONS: Most children with cancer in Latin America are treated in public HVC. There is a scarcity of pediatric oncologists, specialized nurses and surgeons, and palliative care teams, especially in centers with public funding.

Carboplatin desensitization in the era of target therapies: still worthwhile?

PURPOSE: Unresectable pediatric low-grade gliomas (LGG) usually need adjuvant therapy, and carboplatin hypersensitivity reaction (HR) commonly leads to premature treatment cessation of a standard chemotherapy regimen. In the molecular era, advances in understanding tumor genetic characteristics allowed the development of targeted therapies for this group of tumors; however, cost-effectiveness assessment of treatments, especially in low-income countries, is crucial. The aim is to describe the results of carboplatin desensitization protocol in a single center in a middle-income country. METHOD: Prospective analysis of children with LGG submitted to carboplatin desensitization from December 2017 to June 2020 with follow-up until April 2024. RESULTS: Nine patients were included. The mean age was 11 years. Five patients were male. Seven had optic pathway and two cervicomedullary location. Six had histologic diagnosis and four molecular analyses. The incidence of carboplatin reactions during the study period was 39.1%. Six patients underwent skin prick test, three with positive results. The first HR occurred, on average, around the 9th cycle of treatment. All patients had cutaneous symptoms, and five out of nine had anaphylaxis as the first reaction. 77.7% of the patients completed the protocol, and the clinical benefit rate (stable disease and partial response) was 88.8%. Six patients further required other lines of therapy. Monthly, the total cost for carboplatin was $409.09, and for target therapies (dabrafenib plus trametinib), $4929.28 to $5548.57. CONCLUSION: Our study presented an interesting and cost-effective option where desensitization allowed children with HR to be treated with first-line therapy, avoiding the discontinuation of an effective treatment.

International Society of Paediatric Oncology (SIOP) Global Mapping Programme: Latin American Society of Pediatric Oncology (SLAOP) country-level report.

BACKGROUND: Latin American countries are improving childhood cancer care, showing strong commitment to implement the Global Initiative for Childhood Cancer, but there are scant publications of the situation at a continental level. METHODS: As part of the International Society of Paediatric Oncology Global Mapping project, delegates of each country participating in the Latin American Society of Pediatric Oncology (SLAOP) and chairs of national pediatric oncology societies and cooperative groups were invited to provide information regarding availability of national pediatric cancer control programs (NPCCP), pediatric oncology laws, pediatric oncology tumor registries, and training programs and support to diagnosis and treatment. RESULTS: Nineteen of the 20 countries participating in SLAOP responded. National delegates reported nine countries with NPCCP and four of them were launched in the past 5 years. National pediatric tumor registries are available in eight countries, and three provided published survival results. Fellowship programs for training pediatric oncologists are available in 12 countries. National delegates reported that eight countries provide support to most essential diagnosis and treatments and 11 provide partial or minimal support that is supplemented by civil society organizations. Seven countries have a pediatric oncology law. There are three international cooperative groups and four national societies for pediatric oncology. CONCLUSION: Despite many challenges, there were dramatic advances in survivorship, access to treatment, and availability of NPCCP in Latin America. Countries with highest social development scores in general provide more complete support and are more likely to have NPCCP, training programs, and reported survival results.

Intracranial non-germinomatous germ cell tumors in children and adolescents: how can the experience from an uppermiddle-income country contribute to the worldwide effort to improve outcomes?

Background: Non-germinomatous germ cell tumors (NGGCT) accounts for one third of intracranial GCT. While the germinoma group have an excellent overall survival, the standard of practice for children with NGGCT is still under evaluation. Aims: Describe the results of the of the Brazilian consortium protocol. Methods: Since 2013, 15 patients with a diagnosis of NGGCT by histopathology and/or serum/cerebrospinal fluid (CSF) tumor markers, ßHCG >200mlU/ml and/or positive alpha-fetoprotein were treated with neoadjuvant chemotherapy with carboplatin, cyclophosphamide and etoposide followed by ventricular radiotherapy (RTV) of 18Gy with boost (32Gy) to the primary site. Metastatic patients underwent craniospinal irradiation (CSI) and "slow responders" to the four initial cycles of CT, to autologous stem cell transplantation (ASCT) followed by CSI. Results: Mean age, 13.1 years. Thirteen males. Primary sites: pineal (n=12), suprasellar (n=2) and bifocal (n=1). Four patients were metastatic at diagnosis. Eight patients had CSF and/or serum alpha-fetoprotein levels > 1,000ng/ml. Tumor responses after chemotherapy demonstrated complete in six cases and partial in seven, with "second-look" surgery being performed in five cases, and two patients presenting viable lesions being referred to ASCT. The main toxicity observed was hematological grades 3/4. Two patients with metastatic disease, one with Down Syndrome and AFP > 1,000ng/ml and the other with choriocarcinoma and pulmonary metastases, developed progressive disease resulting in death, as well as two other patients without evidence of disease, due to endocrinological disorders. Event-free and overall survival at 2 and 5 years were 80% and 72.7%, respectively, with a mean follow-up of 48 months (range, 7-107). Conclusions: Despite the small number of patients, in our series, treatment with six cycles of chemotherapy and RTV with focal boost for localized disease (n=11) and ACST for identified slow responders (n=2) seem to be effective strategies contributing to the overall effort to improve outcomes of this group of patients.

SIOP pediatric oncology services Global Mapping Program: Latin American data collection.

The International Society of Paediatric Oncology (SIOP) launched a program to map all pediatric cancer facilities around the world. After the results in Africa were completed, the strategy for data collection for Latin America was revised to improve the accuracy and avoid duplications. In partnership with SIOP, the Sociedad Latino Americana de Oncología Pediátrica (SLAOP) approached their delegates who provided the contacts for a 10-question survey about their institutional capacities. Data were collected by email, online meetings, or telephone calls, and stored in a secure platform. All but one country participated and a high number of centers were recorded.

Invasive fungal infections in pediatric patients with central nervous system tumors: novel insights for prophylactic treatments?

Background and aims: Invasive fungal disease (IFD) poses significant morbidity and mortality risks, especially in pediatric patients with neoplastic diseases. However, there is a notable lack of data concerning patients with central nervous system (CNS) tumors. Considering vulnerability factors to infections such as neutropenia, corticosteroids, chemotherapy, surgical interventions, and others, this study aims to evaluate the incidence of IFD in pediatric patients with CNS tumors and determine appropriate indications for prophylactic measures. This is a single-center, retrospective study conducted between 2011 and 2022 at the Pediatric Institute of Oncology (IOP-GRAACC-UNIFESP). Results: A total of 38 cases of IFD were diagnosed in 818 children with CNS malignancies (4,6%). The mean age was 3.5 years (0.4-28y), with 22 (57.9%) male patients. Embryonal tumors (18/38, 47.3%) were the most prevalent CNS tumors, followed by low-grade gliomas (13/38, 34.2%). All episodes met the EORTC IFD criteria, and 36/38 (94.7%) were proven. Invasive yeast infections (33/36, 91.6%), predominantly Candida (30/33, 90.9%), were the most common diagnosis. In total, 25 patients (25/38, 65.8%) were receiving chemotherapy, with 13 of them having embryonal tumors. A total of 11 infants were in the Head Start scheme, resulting in a high prevalence of IFD in these group of patients (11/58, 18.9%). In total, 13 (13/38, 34.2%) patients underwent neurosurgery, mostly ventricular-peritoneal shunts revisions (10/13, 76.9%). Nine (9/38, 23.7%) were with prolonged use of corticosteroids, eight of them associated with neurosurgery. Conclusion: Routine systemic antifungal prophylaxis based solely on diagnosis is not recommended for low-risk cases. Evaluating patient- and treatment-specific risk factors is crucial in infants undergoing high-dose chemotherapy with expected neutropenia and in patients requiring prolonged corticosteroid therapy alongside neurosurgical procedures.

Survival analysis and prognostic factors in posterior fossa ependymomas in children and adolescents.

OBJECTIVE: In this study, the authors aimed to analyze the overall survival (OS) and progression-free survival (PFS) of patients younger than 18 years of age who were diagnosed with posterior fossa ependymomas, and to identify prognostic factors such as the degree of resection, tumor topography, and involvement of the lesion in the hindbrain. METHODS: The authors performed a retrospective cohort study of patients younger than 18 years of age, treated beginning in 2000, with a diagnosis of posterior fossa ependymoma. Ependymomas were separated into three groups: tumors restricted to the fourth ventricle, tumors inside the fourth ventricle and exiting from the foramen of Luschka, and tumors inside the fourth ventricle and completely surrounding the hindbrain. Furthermore, the tumors were classified by molecular group using the staining method for H3K27me3. Statistical analysis was performed using Kaplan-Meier survival curves, with p < 0.05 considered statistically significant. RESULTS: Of 1693 patients who underwent surgical treatment between January 2000 and May 2021, 55 patients who met the inclusion criteria were included. The median age at diagnosis was 2.98 years. The median OS was 44 months, and the survival rates at 1, 5, and 10 years were 92.5%, 49.1%, and 38.3%, respectively. The cases were assigned to two posterior fossa ependymoma molecular groups: 35 (63.6%) cases to group A and 8 (14.5%) to group B. The median ages in groups A and B were 2.94 and 2.85 years and the median OS values were 44 and 38 months, respectively (p = 0.9245). Statistical analysis was performed on multiple variables, including age, sex, histological grade, Ki-67 expression, tumor volume, extent of resection, and adjuvant therapies. The median PFS of patients with dorsal-only involvement was 28 months; for dorsolateral involvement, it was 15 months; and for total involvement, it was 9.5 months (p = 0.0464). No statistically significant difference was found for OS. There was a statistically significant difference between the proportion of patients in whom gross-total resection was achieved in the dorsal-only involvement group (73.1%, 19/26) and those in the total involvement group (0%, 0/6) (p = 0.0019). CONCLUSIONS: This study confirmed that the extent of resection has an impact on OS and PFS. The authors found that adjuvant radiotherapy resulted in a higher OS but did not prevent progression, that the pattern of involvement of the brainstem in the tumor at diagnosis could elicit important information regarding the patient's prognosis regarding PFS, and that the total involvement of the rhombencephalon impaired the gross-total resection of these tumors.

Outcomes and surgical approaches for pineal region tumors in children: 30 years' experience.

OBJECTIVE: Pineal region tumors account for 2.7%-11% of all CNS tumors in children. In this series, the authors present their surgical results and long-term outcomes from a pediatric pineal region tumor cohort. METHODS: A total of 151 children aged 0-18 years were treated from 1991 to 2020. Tumor markers were collected in all patients; if positive, chemotherapy was performed, and if negative, biopsy was performed, preferably endoscopically. Resection was performed when there was a residual germ cell tumor (GCT) lesion after chemotherapy. RESULTS: The distribution based on histological type, as verified by markers, biopsy, or surgery, was germinoma (33.1%), nongerminomatous GCT (NGGCT) (27.2%), pineoblastoma (22.5%), glioma (12.6%), and embryonal tumor (atypical teratoid rhabdoid tumor) (3.3%). A total of 97 patients underwent resection, and gross-total resection (GTR) was achieved in 64%; the highest GTR rate (76.6%) was found in patients with GCTs, and the lowest (30.8%) was found in those with gliomas. The supracerebellar infratentorial approach (SCITA) was the most common, performed in 53.6% of patients, followed by the occipital transtentorial approach (OTA), performed in 24.7% of patients. Lesions were biopsied in 70 patients, and the diagnostic accuracy was 91.4. The overall survival (OS) rates at 12, 24, and 60 months as stratified by histological type were 93.7%, 93.7%, and 88% for patients with germinomas; 84.5%, 63.5%, and 40.7% for patients with pineoblastomas; 89.4%, 80.8%, and 67.2% for patients with NGGCTs; 89.4%, 78.2%, and 72.6% for patients with gliomas; and 40%, 20%, and 0% for patients with embryonal tumors, respectively (p < 0001). The OS at 60 months was significantly higher in the group with GTR (69.7%) than in the group with subtotal resection (40.8%) (p = 0.04). The 5-year progression-free survival was 77% for patients with germinomas, 72.6% for patients with gliomas, 50.8% for patients with NGGCTs, and 38.9% for patients with pineoblastomas. CONCLUSIONS: The efficacy of resection varies by histological type, and complete resection is associated with higher OS rates. Endoscopic biopsy is the method of choice for patients presenting with negative tumor markers and hydrocephalus. For tumors restricted to the midline and with extension to the third ventricle, a SCITA is preferred, whereas for lesions with extension toward the fourth ventricle, an OTA is preferred.

Outcome of Children and Adolescents With Primary Intracranial Germinoma Treated With Chemotherapy and Reduced Dose-Field Irradiation: A Prospective Brazilian Experience.

PURPOSE: This prospective Brazilian single-arm trial was conducted to determine response to chemotherapy and survival after response-based radiotherapy in children with intracranial germinomas, in the setting of a multi-institutional study in a middle-income country (MIC) with significant disparity of subspecialty care. PATIENTS AND METHODS: Since 2013, 58 patients with histologic and/or serum and CSF tumor marker evaluations of primary intracranial germ cell tumors were diagnosed; 43 were germinoma with HCGß levels ≤200 mIU/mL and five between 100 and 200 mIU/mL. The treatment plan consisted of four cycles of carboplatin and etoposide followed by 18 Gy whole-ventricular field irradiation (WVFI) and primary site(s) boost up to 30 Gy; 24 Gy craniospinal was prescribed for disseminated disease. RESULTS: Mean age 13.2 years (range, 4.7-25.5 years); 29 were males. Diagnosis was made by tumor markers (n = 6), surgery (n = 25), or both (n = 10). Two bifocal cases with negative tumor markers were treated as germinoma. Primary tumor location was pineal (n = 18), suprasellar (n = 14), bifocal (n = 10), and basal ganglia/thalamus (n = 1). Fourteen had ventricular/spinal spread documented by imaging studies. Second-look surgery occurred in three patients after chemotherapy. Thirty-five patients achieved complete responses after chemotherapy, and eight showed residual teratoma/scar. Toxicity was mostly grade 3/4 neutropenia/thrombocytopenia during chemotherapy. At a median follow-up of 44.5 months, overall and event-free survivals were 100%. CONCLUSION: The treatment is tolerable, and WVFI dose reduction to 18 Gy preserves efficacy; we have demonstrated the feasibility of successfully conducting a prospective multicenter trial in a large MIC despite resource disparity.

Diencephalic syndrome-like presentation of brainstem tumor: a series case-based review.

PURPOSE: Russel described a rare clinical entity known as diencephalic syndrome (DS) in 1951, which was traditionally caused by a neoplasm in the hypothalamic-optic chiasmatic region. DS is characterized by severe emaciation despite adequate or slightly reduced caloric intake, locomotor hyperactivity, euphoria and other minor features. Current evidence suggests that a rare population of children with a similar phenotype may have their tumor located in the posterior fossa instead, defining the DS-like presentation, a rare entity with few cases reported in the literature. METHODS: A thorough search of three databases (PubMed, Ovid Medline, and Ovid Embase) was conducted to identify relevant papers reporting children with DS associated with brainstem tumors. To our knowledge, only seven cases have been documented in the literature. Moreover, we present four of our own cases, focusing on the unusual clinical presentation, the diagnosis process, and the lag time between the initial symptoms and the definitive diagnosis. RESULTS: In this review, the mean lag time between the onset of symptoms and diagnosis was 20.9 months (median: 16 months; range: 1.5-72 months), whereas in our series of cases, the time was 32.5 months (median: 33 months; range: 7-57 months). CONCLUSION: Despite recent significant advances in neuro-oncology diagnostic tools, this mean lag time did not improve when compared with the previous literature review from 1976. Throughout these data, we aim to raise awareness in the hopes of detecting intracranial neoplasms earlier in cases of children with profound emaciation of unknown cause.

Risk for hydrocephalus, hygroma, and tumor dissemination after ventricular opening during resection of supratentorial neoplasms in children.

PURPOSE: The possibility that ventricular opening generates postoperative complications after surgical tumor treatment often restricts the degree of tumor resection. This study aims to determine whether the ventricular opening is associated with more complications in surgeries for resectioning supratentorial intra-axial brain tumors in the pediatric population. METHODS: A retrospective review analysis was performed of patients treated at IOP/GRAACC between 2002 and 2020 under 19 years of age and underwent surgery for supratentorial intra-axial primary brain tumor resection. Data were collected from 43 patients. RESULTS: Glial tumor was more common than non-glial (65% vs. 35%, p = 0.09). The ventricular opening was not related to neoplastic spreads to the neuroaxis (6% vs. 0, p > 0.9) or leptomeningeal (3% vs. 0, p > 0.9). Of the patients whose ventricle was opened, 10% developed hydrocephalus requiring treatment, while none of the patients in the group without ventricular opening developed hydrocephalus (p = 0.5). There was also no statistical difference regarding ventriculitis. Postoperative subdural hygroma formation correlated with the ventricular opening (43% vs. 0, p = 0.003). The survival at 1, 5, and 10 years of cases with the ventricular opening was 93.2%, 89.7%, and 75.7%, respectively, while in cases without ventricular opening, it was 100%, 83%, and 83%, respectively, respectively, with no statistical difference between the mortality curves. CONCLUSION: Our study demonstrated that ventricular violation was not associated with the occurrence of significant complications. It was related to the formation of subdural hygroma, which did not require additional treatment.

Outcomes of Infants and Young Children With Relapsed Medulloblastoma After Initial Craniospinal Irradiation-Sparing Approaches: An International Cohort Study.

PURPOSE: Infant and young childhood medulloblastoma (iMB) is usually treated without craniospinal irradiation (CSI) to avoid neurocognitive late effects. Unfortunately, many children relapse. The purpose of this study was to assess salvage strategies and prognostic features of patients with iMB who relapse after CSI-sparing therapy. METHODS: We assembled a large international cohort of 380 patients with relapsed iMB, age younger than 6 years, and initially treated without CSI. Univariable and multivariable Cox models of postrelapse survival (PRS) were conducted for those treated with curative intent using propensity score analyses to account for confounding factors. RESULTS: The 3-year PRS, for 294 patients treated with curative intent, was 52.4% (95% CI, 46.4 to 58.3) with a median time to relapse from diagnosis of 11 months. Molecular subgrouping was available for 150 patients treated with curative intent, and 3-year PRS for sonic hedgehog (SHH), group 4, and group 3 were 60%, 84%, and 18% (P = .0187), respectively. In multivariable analysis, localized relapse (P = .0073), SHH molecular subgroup (P = .0103), CSI use after relapse (P = .0161), and age ≥ 36 months at initial diagnosis (P = .0494) were associated with improved survival. Most patients (73%) received salvage CSI, and although salvage chemotherapy was not significant in multivariable analysis, its use might be beneficial for a subset of children receiving salvage CSI < 35 Gy (P = .007). CONCLUSION: A substantial proportion of patients with relapsed iMB are salvaged after initial CSI-sparing approaches. Patients with SHH subgroup, localized relapse, older age at initial diagnosis, and those receiving salvage CSI show improved PRS. Future prospective studies should investigate optimal CSI doses and the role of salvage chemotherapy in this population.

Multi-institutional analysis of central nervous system germ cell tumors in patients with Down syndrome.

PURPOSE: Primary germ cell tumors (GCTs) are the most common central nervous system (CNS) neoplasm in patients with Down syndrome (DS). However, a standard of care has not been established due to paucity of data. METHODS: A retrospective multi-institutional analysis was conducted, in addition to a comprehensive review of the literature. RESULTS: Ten patients from six institutions (five USA, one Brazil) were identified, in addition to 31 patients in the literature from 1975 to 2021. Of the 41 total patients (mean age 9.9 years; 61% male), 16 (39%) had non-germinomatous germ cell tumors (NGGCTs), 16 (39%) had pure germinomas, and eight (19.5%) had teratomas. Basal ganglia was the most common tumor location (n = 13; 31.7%), followed by posterior fossa (n = 7; 17%). Nine patients (22%) experienced disease relapse or progression, of which four died from tumor progression (one germinoma, three teratomas). Sixteen patients (39%) experienced treatment-related complications, of which eight (50%) died (five germinomas, three NGGCTs). Of the germinoma patients, two died from chemotherapy-related sepsis, one from postsurgery cardiopulmonary failure, one from pneumonia, and one from moyamoya following radiation therapy (RT). Of the NGGCT patients, one died from chemotherapy-related sepsis, one from postsurgical infection, and one from pneumonia following surgery/chemotherapy/RT. Three-year overall survival was 66% for all histological types: 62% germinomas, 79% for NGGCTs, and 53% for teratomas. CONCLUSION: Patients with DS treated for CNS GCTs are at an increased risk of treatment-related adverse events. A different therapeutic approach may need to be considered to mitigate treatment-related complications and long-term neurocognitive sequelae.

Impact of COVID-19 in pediatric oncology care in Latin America during the first year of the pandemic.

BACKGROUND: The ongoing coronavirus 2019 disease (COVID-19) pandemic strained medical systems worldwide. We report on the impact on pediatric oncology care in Latin American (LATAM) during its first year. METHOD: Four cross-sectional surveys were electronically distributed among pediatric onco-hematologists in April/June/October 2020, and April/2021 through the Latin American Society of Pediatric Oncology (SLAOP) email list and St Jude Global regional partners. RESULTS: Four hundred fifty-three pediatric onco-hematologists from 20 countries responded to the first survey, with subsequent surveys response rates above 85%. More than 95% of participants reported that treatment continued without interruption for new and active ongoing patients, though with disruptions in treatment availability. During the first three surveys, respondents reported suspensions of outpatient procedures (54.2%), a decrease in oncologic surgeries (43.6%), radiotherapy (28.4%), stem cell transplants (SCT) (69.3%), and surveillance consultations (81.2%). Logistic regression analysis showed that at the beginning of the first wave, participants from countries with healthcare expenditure below 7% were more likely to report a decrease in outpatient procedures (odds ratio [OR]: 1.84, 95% CI: 1.19-2.8), surgeries (OR: 3, 95% CI: 1.9-4.6) and radiotherapy (OR: 6, 95% CI: 3.5-10.4). Suspension of surveillance consultations was higher in countries with COVID-19 case fatality rates above 2% (OR: 3, 95% CI: 1.4-6.2) and SCT suspensions in countries with COVID-19 incidence rate above 100 cases per 100,000 (OR: 3.48, 95% CI: 1.6-7.45). Paradoxically, at the beginning of the second wave with COVID-19 cases rising exponentially, most participants reported improvements in cancer services availability. CONCLUSION: Our data show the medium-term collateral effects of the pandemic on pediatric oncology care in LATAM, which might help delineate oncology care delivery amid current and future challenges posed by the pandemic.

Reduction in the cerebrospinal fluid protein level after bevacizumab treatment in patients with optic pathway low-grade gliomas.

Optic pathway gliomas (OPG) can cause elevated cerebrospinal fluid (CSF) protein concentrations. We report on two patients with suprasellar low-grade gliomas and high CSF protein levels (590 and 551 mg/dl) that precluded shunt implantation. After two and three doses of bevacizumab, respectively, the levels dropped dramatically to 191 and 178 mg/dl, respectively. Bevacizumab treatment was associated with a decrease in CSF protein level, allowing successful shunt placement. Our results are consistent with the pharmacological mechanism of bevacizumab, which decreases protein leakage from blood vessels to the ventricles.

Multi-institutional analysis of treatment modalities in basal ganglia and thalamic germinoma.

BACKGROUND: Central nervous system (CNS) germinomas are treatment-sensitive tumors with excellent survival outcomes. Current treatment strategies combine chemotherapy with radiotherapy (RT) in order to reduce the field and dose of RT. Germinomas originating in the basal ganglia/thalamus (BGTGs) have proven challenging to treat given their rarity and poorly defined imaging characteristics. Craniospinal (CSI), whole brain (WBI), whole ventricle (WVI), and focal RT have all been utilized; however, the best treatment strategy remains unclear. METHODS: Retrospective multi-institutional analysis has been conducted across 18 institutions in four countries. RESULTS: For 43 cases of nonmetastatic BGTGs, the 5- and 10-year event-free survivals (EFS) were 85.8% and 81.0%, respectively, while the 5- and 10-year overall survivals (OS) were 100% and 95.5%, respectively (one patient fatality from unrelated cause). Median RT doses were as follows: CSI: 2250 cGy/cGy(RBE) (1980-2400); WBI: 2340 cGy/cGy(RBE) (1800-3000); WVI: 2340 cGy/cGy(RBE) (1800-2550); focal: 3600 cGy (3060-5400). Thirty-eight patients (90.5%) received chemotherapy. There was no statistically significant difference in the EFS based on initial field extent (p = .84). Nevertheless, no relapses were reported in patients who received CSI or WBI. Chemotherapy alone had significantly inferior EFS compared to combined therapy (p = .0092), but patients were salvageable with RT. CONCLUSION: Patients with BGTGs have excellent outcomes and RT proved to be an integral component of the treatment plan. This group of patients should be included in future prospective clinical trials and the best RT field should be investigated further.

Grating visual acuity impairment assessed by sweep visually evoked potentials in children with optic pathway tumors unable to perform optotype acuity tests / Deficiência na acuidade visual de grades avaliada pelos potenciais visuais evocados de varredura em crianças com tumores da via óptica incapazes de informar a acuidade de optotipos

ABSTRACT Purpose: To determine visual impairment due to optic pathway tumors in children unable to perform recognition acuity tests. Methods: Grating visual acuity scores, in logMAR, were obtained by sweep visually evoked potentials (SVEP) in children with optic pathway tumors. The binocular grating visual acuity deficit was calculated by comparison with age-based norms and then assigned to categories of visual impairment as mild (from 0.10 to 0.39 logMAR), moderate (from 0.40 to 0.79 logMAR), or severe (≥0.80 logMAR). Interocular differences were calculated by subtraction and considered increased if >0.10 logMAR. Results: The participants were 25 children (13 boys; mean ± SD age, 35.1 ± 25.9 months; median age, 32.0 months) with optic pathway tumors (24 gliomas and 1 embryonal tumor), mostly located at the hypothalamic-chiasmatic transition (n=21; 84.0%) with visual abnormalities reported by parents (n=17; 68.0%). The mean grating acuity deficit was 0.60 ± 0.36 logMAR (median, 0.56 logMAR). Visual impairment was detected in all cases and was classified as mild in 10 (40.0%), moderate in 8 (32.0%), and severe in 7 (28.0%) children, along with increased interocular differences (>0.1 logMAR) (n=16; 64.0%). The remarkable ophthalmological abnormalities were nystagmus (n=17; 68.0%), optic disc cupping and/or pallor (n=13; 52.0%), strabismus (n=12; 48.0%), and poor visual behavior (n=9; 36.0%). Conclusion: In children with optic pathway tumors who were unable to perform recognition acuity tests, it was possible to quantify visual impairment by sweep-visually evoked potentials and to evaluate interocular differences in acuity. The severity of age-based grating visual acuity deficit and interocular differences was in accordance with ophthalmological abnormalities and neuroimaging results. Grating visual acuity deficit is useful for characterizing visual status in children with optic pathway tumors and for supporting neuro-oncologic management.(AU)

RESUMO Objetivo: Determinar o grau de deficiência visual em crianças com tumores da via óptica incapazes de informar a acuidade visual de reconhecimento. Método: A acuidade visual de grades, em logMAR, foi estimada por potenciais visuais evocados de varredura em crianças com tumores das vias ópticas. O déficit da acuidade visual de grades binocular foi calculado em relação ao valor mediano normativo esperado para a idade e a deficiência visual, classificada como leve (0,10 a 0,39 logMAR), moderada (0,40 a 0,79 logMAR) ou grave (≥0,80 logMAR). Diferenças inter-oculares foram calculadas por subtração e consideradas aumentadas se >0,10 logMAR. Resultados: Foram avaliadas 25 crianças (13 meninos; média de idade ± DP=35,1± 25,9 meses; mediana=32,0 meses) com tumores da via óptica (24 gliomas e 1 tumor embrionário) localizados particularmente na transição hipotalâmico-quiasmática (n=21; 84,0%) e com anormalidades visuais detectadas pelos pais (n=17; 68,0%). A média do déficit da acuidade de grades foi 0,60 ± 0,36 logMAR (mediana=0,56 logMAR). Observou-se deficiência visual leve em 10 (40,0%), moderada em 8 (32,0%) e grave em 7 (28,0%), além de aumento da diferença interocular da acuidade visual (n=16; 64,0%). As principais alterações oftalmológicas encontradas foram: nistagmo (n=17; 68,0%), aumento da escavação do disco óptico e/ou palidez (n=13; 52,0%), estrabismo (n=12; 48,0%) e comportamento visual pobre (n=9; 36,0%). Conclusão: Em crianças com tumor da via óptica e incapazes de responder aos testes de acuidade visual de reconhecimento, foi possível quantificar deficiência visual por meio dos potenciais visuais evocados de varredura e avaliar a diferença interocular da acuidade visual de grades. A gravidade do déficit da acuidade visual de grades relacionado à idade e a diferença interocular da acuidade visual de grades foram congruentes com alterações oftalmológicas e neuroimagem. O déficit da acuidade visual de grades foi útil à caracterização do estado visual em crianças com tumores da via óptica e ao embasamento da assistência neuro-oncológica.(AU)