Society Of Pediatric Oncology Research Articles

Similarities and controversies in imaging of pediatric renal tumors: A SIOP-RTSG and COG collaboration.

Malignant renal tumors are rare in children, and Wilms tumors (WTs) are the most common subtype. Imaging plays an essential role in the diagnosis, staging, and follow-up of these patients. Initial workup for staging is mainly performed by cross-sectional imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI). Imaging approach within the two core international groups, the Children's Oncology Group (COG, North America) and the International Society of Pediatric Oncology - Renal Tumor Study Group (SIOP-RTSG, Europe), differs. Whereas abdominal ultrasound (US) is used for the initial diagnosis of a suspected pediatric renal tumor globally, COG protocols support the use of CT or MRI for locoregional staging, contrary to the preference for MRI over CT for abdominopelvic evaluation within the SIOP-RTSG. The purpose of this manuscript is to summarize current imaging approaches, highlighting differences and similarities within these core international groups, while focusing on future innovative efforts and collaboration within the HARMONICA initiative.

Applications of the Grading Scales for the Detection of Ototoxicity in Children after Treatment of Neuroblastoma and Extracranial Germinal Tumor

Introduction: Advances in treatment have resulted in a significant increase in survival rates for patients cured of malignant diseases such as neuroblastoma (NBL) and extracranial germ cell tumor (GCT). NBL is one of the pediatric cancers during which potentially ototoxic cytostatic drugs (cisplatin and carboplatin) are used for treatment. Other cancers include germinal tumors, hepatoblastoma, sarcomas, and brain tumors. Often, this very aggressive treatment has a high risk of causing long-term side effects, including hearing loss. Hence, the present study aimed to evaluate the usefulness of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Brock, Chang, and International Society of Pediatric Oncology (SIOP) Boston scales in terms of detecting the high-frequency nature of hearing loss induced by ototoxic drugs and monitoring hearing status in children after completion of oncological treatment. Additionally, the frequency of hearing loss in children treated for NBL and extracranial GCT was assessed, and the principles of monitoring hearing in these patients were indicated. Methods: The study group consisted of 78 patients diagnosed with NBL (n = 47) and GCT (n = 31). There were 23 boys and 24 girls in the NBL group, aged 0–16 years, and 21 boys and 10 girls in the GCT group, aged 0–18 years. The control group consisted of 54 patients who had never received oncological treatment, were not taking potentially ototoxic drugs, and appeared socially efficient in the subjective audiological assessment. Audiometric examinations and DP-acoustic otoemission measurements were performed. Additionally, impedance audiometry tests were done to exclude a possible conductive component of the hearing loss. Results: The analysis shows that ototoxicity-induced hearing loss was observed in 13.8–65.5% of children. 75.9% of patients showed hearing loss in the 16 kHz frequency range, and at least 56.8% of patients showed hearing loss in the frequency range above 12.5 kHz. Hearing impairment, relevant to speech understanding, was displayed by more than 40% of children treated for NBL and GCT. Conclusions: The confirmation of hearing loss in nearly 65% of cases in both patients indicates the necessity to monitor the long-term side effects of anticancer treatment. Acoustic otoemission measurements, the adoption of articulatory indices based on an audiogram, or the use of arbitrary ototoxicity assessment scales such as Brock, Chang, or SIOP Boston are fully justified techniques for studying ototoxicity induced by cytostatic drugs. However, they all require continuous improvement to increase their sensitivity and specificity, especially in the pediatric group.

Pediatric Acute Myeloid Leukemia in India: A Systematic Review

Abstract Background Lower-middle-income countries face unique problems in the management of pediatric acute myeloid leukemia (AML) due to which the outcomes have not kept pace with developed nations. In India, data on childhood AML is sparsely available, thus making a true assessment of disease trends difficult. The current systematic review was undertaken to assess the outcomes of childhood AML from published literature from India over a period of 10 years (2011–2021). Materials and Methods A systematic search of MEDLINE, Google Scholar, and SCOPUS was performed as per preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement from January 1, 2011 to December 31, 2021. In addition, International Society of Pediatric Oncology (SIOP) conference abstracts were also screened for relevant studies on AML from India. This study was registered in PROSPERO (ID42021273218). Results A total of 1,210 patients from 19 studies were included. Standard 3 + 7 and MRC AML based regimens were commonly adopted regimens for induction. Remission rates varied between 56 and 95%. Overall treatment-related mortality across studies was 23.2% (95% confidence interval [CI]: 10.3–35.9%). The mean incidence of treatment abandonment was 19.3% ( 95% CI: 10.9–27.5%). Event-free survival and overall survival were in the range of 28 to 55% and 15 to 66%, respectively. Hematopoietic stem cell transplantation was performed only on a small subset of patients. Conclusion Outcomes of pediatric AML in India continue to be suboptimal with high treatment abandonment and toxic deaths. Ensuring uniform access to therapy and supportive care along with a robust social support system would improve outcomes of childhood AML in India.

The Incidence and Risk Factors of Cisplatin and Carboplatin Ototoxicity in Pediatric Oncology Patients at Tertiary Oncology Center.

Pediatric cancers are relatively rare diseases when considering all types of cancer. Platinum-based chemotherapeutic agents are potent agents against a variety of pediatric malignancies. An important adverse effect of platinum-based agents is the occurrence of hearing loss. This hearing loss can pose a challenge to detect especially if the child is in his early of life. It will also significantly affect the child development of social, pedagogical, and personal dimensions. It is integral to identify incidence of platinum-based ototoxicity and risk factors that increase the likelihood of developing hearing loss in cancer children. We performed a retrospective chart review of 123 pediatric patients who had completed cisplatin and carboplatin therapy for a variety of malignancies. Patients were diagnosed at Princess Nourah Oncology Centre between January 2011 and December 2016, were less than 14years old at diagnosis. Audiograms were scored using the International Society of Pediatric Oncology (SIOP) Boston Scale (0-4), a validated grading system for cisplatin-related hearing loss. Ototoxicity was reported in 16 patients out of 123 with a rate of 13%. The incidence of ototoxicity was highest in CNS tumors such as medulloblastoma (37.5%) and optic glioma (25%). Males were at greater risk for developing hearing loss than females. Cumulative cisplatin dose and addition radiation therapy were also identified as risk factors for development of ototoxicity (P = 0.008). Nature and location of cancer, gender, cumulative dose, and addition of radiation therapy are important clinical biomarkers of cisplatin ototoxicity.

A higher tumor volume and undernutrition at diagnosis adversely affect the survival of children with Wilms tumor: A study of 200 patients.

Distinct prognostic factors for Wilms tumor (WT) in low- and middle-income countries need identification. Retrospective study of patients with WT managed by the International Society of Pediatric Oncology (SIOP) approach for over 11 years (2005-2016) at a single center in Chandigarh, India. The study included 200 patients (median age: 33.5 months). The tumor stage (SIOP) distribution included stage I (30%), II (36%), III (14%), IV (17%), and V (3%). The histology-risk groups were low (8%), intermediate (84%), and high risk (9%). At diagnosis, 68 out of 190 (36%) patients were underweight. The median tumor volume at diagnosis was 481ml (interquartile ratio [IQR]: 306.9, 686.8, n=146). Following neoadjuvant chemotherapy, it reduced to 110ml (IQR: 151.2, 222, n=77). Treatment was abandoned in 20.5% of the patients. Treatment-related mortality occurred in 13 of 179 (7.2%) patients. Relapse occurred in 26 of 158 (16.5%) patients. The 3-year overall survival (OS) and event-free survival (EFS) of patients who completed therapy were 78.3 and 72%, respectively. The stage (p=.013) and histology (p=.023) influenced OS. A lower OS in stage II (75.4%) versus stage III disease (83.7%) suggested understaging. Patients with a higher tumor volume at diagnosis (p=.005; odds ratio [OR]: 0.99; 95% confidence interval [CI]: 0.99-1.00) or a lower weight-for-age z-score (p=.002; OR: 1.68; 95% CI: 1.21-2.33) had an increased risk of death or relapse. The 3-year OS and EFS of children who completed therapy were 78.3 and 72%, respectively. A higher tumor volume and lower weight-for-age z-score at diagnosis were identified as distinct adverse prognostic factors. A likely suboptimal lymph node assessment (intraoperative and histopathology) contributed to the understaging of stage III to II disease and reduced survival.

Conference report on the 14th International Society of Paediatric Oncology African Continental Meeting, 16-18 March 2022, Kampala, Uganda.

Together with the Africa Continental Branch of the International Society of Paediatric Oncology (SIOP Africa), the Uganda Cancer Institute, a tertiary governmental institution for specialised cancer care services, research and training, hosted the 14th continental meeting of SIOP Africa from the 16–18 March 2022. Under the conference theme, ‘Innovate for Africa’, the hybrid conference brought together close to 400 international delegates to discuss innovations and experiences, as well as share the latest research in the field of paediatric oncology. The World Health Organisation 2030 Global Initiative for Childhood Cancer provided the main starting point for the conference with a comprehensive pre-conference workshop programme, from multiple stakeholders and organisations and the themes for the plenaries towards improving survival to the main breakout sessions. Delegates discussed various ways of improving outcomes in Africa, despite the challenges faced individually and collectively ranging from education, management systems and treatment guidelines to future governmental and NGO involvement in African cancer care. The main achievements of the conference were various commitments for collaboration, investing in junior investigators, development of registries and systems for improved childhood care on the African continent, while working towards greater access to advanced management options such as targeted therapies and bone marrow transplant services.

Availability of essential medicines for children with cancer in Sri Lanka: a prospective cohort study

The WHO Model List of Essential Medicines for children (2019 version) contains 39 antineoplastic and supportive medicines deemed essential for the successful treatment of children with cancer. The availability of these medicines varies across countries, but most reports are retrospective or short term. This study tracked the availability of these medicines in Sri Lanka's only treatment centre for childhood cancer, the National Cancer Institute of Sri Lanka, over 1 year, and examined initial mitigation strategies and implications. We prospectively tracked the availability of essential medicines at the National Cancer Institute of Sri Lanka in a customised database from April 1, 2019, to March 31, 2020. Consumption volumes and unit prices were extracted from the Sri Lankan Ministry of Health's Medical Supplies Management Information System. Availability was mapped against regimens used to treat childhood cancers, including WHO Global Initiative for Childhood Cancer index cancers, in Sri Lanka and by the International Society of Paediatric Oncology. Descriptive analyses and linear regression were used to assess factors associated with the unavailability of medicines. 31 (79%) of 39 medicines listed in the WHO Model List of Essential Medicines for children are in the Sri Lankan Essential Medicine List and 36 (92%) of 39 (48 formulations) are registered for use. Thioguanine, arsenic, and realgar-Indigo naturalis were the unregistered medicines. Over the study period, less than half (17 [44%]) of medicines were consistently available for 100% of the study period, 14 (36%) were available 75-100% of the study period, three (8%) between 50-75% of the study period, and two (5%) for less than 50% of the duration of the study period. The least available drug was procarbazine (available only on 212 [58%] of 366 days in the total study period). The availability of medicines did not reach 100% on any day in the study period. No substantial monthly variability was noted, but the best availability was in August, 2019, and the worst in January, 2020. Applying regimen-based analyses for acute lymphoblastic leukaemia, 12 stockout episodes affected seven (18%) medicines (median 37·5 consecutive days, IQR 12·0-62·0), whereas stockout mitigation strategies (low stock periods not resulting in stockout) were effective in 11 instances; only three (8%) medicines did not have alternate formulations or substitutions during stockouts (vincristine, cytarabine, and mercaptopurine). Of the WHO Global Initiative for Childhood Cancer index cancers, Hodgkin lymphoma was the most affected by stockouts, and retinoblastoma was the least affected. Annual consumption volumes (p=0·13), unit cost (p=0·5), and annual costs per medicine (p=0·091) were not significantly associated with medicine unavailability. Non-availability of essential medicines is an important problem to be addressed for children with cancer in Sri Lanka. This study showed the feasibility of prospective essential medicines tracking at the point-of-care, and how data visibility can inform stock and inventory management and help to identify mitigation strategies for stockouts. None.

Cerebral sinovenous thrombosis and asparaginase re-exposure in patients aged 1-45 years with acute lymphoblastic leukaemia: A NOPHO ALL2008 study.

Cerebral sinovenous thrombosis (CSVT) is a serious complication during asparaginase therapy in patients with acute lymphoblastic leukaemia (ALL). We identified 46 patients with CSVT among 2651 patients (1‒45 years) treated according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol between 2008 and 2018. CSVT cases were prospectively registered in the NOPHO database with retrospective updates. We examined the frequency of asparaginase re‐exposure after CSVT, potential factors associated with asparaginase truncation, and sequelae after CSVT. This work was supported by the Danish Cancer Society and the Danish Childhood Cancer Foundation. The 2.5‐year cumulative incidence of CSVT was 1.9% (95% confidence interval 1.4%–2.5%). The majority of patients (74%, n = 31) were re‐exposed to asparaginase (with low‐molecular‐weight heparin coverage), one of whom had a second CSVT, without neurological sequelae. Patients re‐exposed to asparaginase were earlier in ALL treatment and lacked more asparaginase doses than non‐re‐exposed patients at CSVT diagnosis (median 50 vs. 81 days, p = 0.03; mean 11.2 vs. 8.4 asparaginase doses, p = 0.04). No other examined factors had an impact on asparaginase re‐exposure. At the last follow‐up (median 4.5 years after CSVT), 61% of patients had normal neurological status, and 57% had complete recanalisation of CSVT, with no significant difference between patients re‐exposed and non‐re‐exposed to asparaginase. Our results indicate that re‐exposure to asparaginase is safe after CSVT during anticoagulation.

LGG-10. Evaluation of the chemotherapy efficacy of children with optic pathway glioma in a tertiary hospital in China

OBJECTIVE: In order to analyze the chemotherapy efficacy of children with optic pathway glioma (OPG), the clinical, treatment and prognosis factors of children with OPG who received the German International Society of Pediatric Oncology (SIOP) low-grade glioma (LGG) 2004 regimen chemotherapy, were retrospectively analyzed. METHOD: From September 2014 to October 2019, a total of 60 patients with OPG were enrolled and accept LGG 2004 chemotherapy in the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, China. The progression-free survival (PFS) rates and overall survival (OS) rates were analyzed by the Kaplan-Meier method. Both univariate and multivariate analyses were performed using the Cox-proportional hazards model. The test standard α=0.05. RESULTS: Until January 1st, 2022, all children were alive, and the clinical symptoms were improved at any degree, and well tolerated during the whole treatment. The median follow-up time was 3.7 years (range 2.3-7.1 years), the average time of objective response was 6.8 months (range from 2 to 21 months), and the 5 year PFS rates were 73.0 ± 7.24 %. However, about 3 to 8 months later, 8 cases (age <4 years) relapsed which attained partial remission (PR) at the end of the whole therapy. These relapsed cases were performed the LGG 2004 regimen again, and all had an objective response after 4~6 courses of treatment. In addition, two children (age>8 years old) progressed rapidly during treatment, and had to be performed local radiotherapy and reached complete remission (CR). Another two cases with BRAF V600E mutation, reached a significant remission after 3 months of targeted therapy with selumetinib. Furthermore, the COX multivariate analysis shows that spinal metastasis is an independent risk factor of prognosis of children with OPG. CONLUSIONS: Chemotherapy can improve the clinical efficacy of children with OPG, which is better when combining with bevacizumab and/or targeted therapy.

GCT-14. The Impact of Residual Disease on the Outcomes of Central Nervous System Germinomas – A Single Institution Experience

BACKGROUND: CNS Germinomas are highly radio-sensitive tumors with an excellent survival rate of more than 90%. The current standard of care combines chemotherapy with reduced-dose radiotherapy to minimize the adverse effects and long-term effects associated with radiotherapy. In the latest Children’s Oncology Group clinical trial (ACNS1123 stratum 2), patients with residual or progressive disease following chemotherapy can be considered for a “second-look” surgery to assess tumor viability. Patients with residual disease who do not undergo second-look surgery receive 24 Gy of whole ventricular radiation with a 12 Gy boost compared to 18 Gy plus boost given to patients in complete remission or without viable tumor on second-look. Conversely, the International Society of Paediatric Oncology (SIOP) protocol does not stratify based on response to chemotherapy, and the Korean SMC GCT trial uses 18 Gy CSI plus boost for all patients regardless of chemotherapy response. METHODS: Single center retrospective chart review of germinoma patients treated at St Louis Children’s Hospital between 2011 and 2021. RESULTS: We analyzed data for all 15 germinoma patients treated between 2011 and 2021. Five patients had residual disease following chemotherapy. Of these five, one had complete remission at the end of radiotherapy, one had partial response, and three had stable disease. All patients remain relapse-free with time of follow-up ranging between 6.3-109.3 months from the end of therapy (median 24 months). CONCLUSION: None of the five patients with residual disease following chemotherapy demonstrated disease progression following chemotherapy and radiotherapy. Future prospective clinical trials are needed in order to test the possibility of treating germinomas patients who have residual disease after chemotherapy with a low dose of radiotherapy similar to that used in patients with complete remission.

QOL-13. Impact of hearing loss on neuropsychological functioning in children treated for medulloblastoma: A report from the Children’s Oncology Group (COG)

BACKGROUND/OBJECTIVE: We prospectively examined neuropsychological outcomes and ototoxicity in children with average-risk medulloblastoma. METHODS: Eligible patients included those treated on COG protocol ACNS0331 who completed audiograms at end of therapy or one-year off-therapy, and neuropsychological assessments between 2- and 5-years post-diagnosis. Conventional pure-tone audiometric evaluations (0.25-8kHz) were assigned an ototoxicity grade based on the International Society of Pediatric Oncology (SIOP) grading scale. Grade for the better hearing ear was used for analyses. Participants were divided into two groups: SIOP grade≥3 hearing loss (HL) versus SIOP grade<3. Cutoff score of 60 on BASC-2 was used to dichotomize parent-reported anxiety and depression scores as ‘low’ or ‘high’. RESULTS: Data were available for 113 children (66% male; 86% white), aged 3.0-18.5 at diagnosis (Mean=9.1). One-quarter (24.8%, n=28) had at least moderate HL (≥ SIOP grade 2), and 12.3% (n=14) had severe HL (≥ SIOP grade 3). After controlling for radiation exposure and age, children with severe HL showed significantly higher levels of anxiety (OR=5.9, 95%CI 1.3-26.0, p=0.0195) and borderline differences in depression (OR=4.0, 95%CI 1.0-16.5, p=0.0563), but no differences in cognitive functioning when compared to other participants. When moderate and severe HL were combined in exploratory analyses, significantly greater anxiety (OR=9.0, 95%CI 2.1-37.4, p=.0027) and depression (OR=4.6, 95%CI 1.3-15.7, p=.0165) were observed. CONCLUSIONS: Survivors of pediatric medulloblastoma with moderate to severe HL evidenced greater psychosocial, but not neurocognitive, difficulties compared to those with no or mild HL. It may be that modern treatment protocols generally preserve cognitive functioning such that associations between HL and cognitive impairment are no longer significant. It is also possible that neurocognitive risk associated with HL may not manifest until survivors are further from diagnosis. In contrast, survivors with HL may be at greater risk for negative psychosocial adjustment, suggesting that increased monitoring of mental health outcomes is warranted.

Defining Essential Childhood Cancer Medicines to Inform Prioritization and Access: Results From an International, Cross-Sectional Survey.

PURPOSEAccess to essential cancer medicines is a major determinant of childhood cancer outcomes globally. The degree to which pediatric oncologists deem medicines listed on WHO's Model List of Essential Medicines for Children (EMLc) essential is unknown, as is the extent to which such medicines are accessible on the front lines of clinical care.METHODSAn electronic survey developed was distributed through the International Society of Pediatric Oncology mailing list to members from 87 countries. Respondents were asked to select 10 cancer medicines that would provide the greatest benefit to patients in their context; subsequent questions explored medicine availability and cost. Descriptive and bivariate statistics compared access to medicines between low- and lower-middle–income countries (LMICs), upper-middle–income countries (UMICs), and high-income countries (HICs).RESULTSAmong 159 respondents from 44 countries, 43 (27%) were from LMICs, 79 (50%) from UMICs, and 37 (23%) from HICs. The top five medicines were methotrexate (75%), vincristine (74%), doxorubicin (74%), cyclophosphamide (69%), and cytarabine (65%). Of the priority medicines identified, 87% (27 of 31) are represented on the 2021 EMLc and 77% (24 of 31) were common to the lists generated by LMIC, UMIC, and HIC respondents. The proportion of respondents indicating universal availability for each of the top medicines ranged from 9% to 46% for LMIC, 25% to 89% for UMIC, and 67% to 100% for HIC. Risk of catastrophic expenditure was more common in LMIC (8%-20%), compared with UMIC (0%-28%) and HIC (0%).CONCLUSIONMost medicines that oncologists deem essential for childhood cancer treatment are currently included on the EMLc. Barriers remain in access to these medicines, characterized by gaps in availability and risks of catastrophic expenditure for families that are most pronounced in low-income settings but evident across all income contexts.

Securing access to innovative anticancer therapies for children, adolescents, and young adults outside clinical trials: The SACHA study of the French Society of Pediatric Oncology (SFCE).

10006 Background: Access to innovative anticancer therapies for children, adolescents and young adults within clinical trials in France is steadily increasing in the last years. However, current clinical trials portfolios are still inadequate and thus pediatric hemato-oncologists regularly prescribe innovative medicines outside their marketing authorization, and/or experimental drugs through compassionate use. Methods: The Secured Access to innovative medicines for CHildren with cAncer (SACHA) is a French prospective observational study developed by the French Society of Pediatric Oncology (SFCE) with Gustave Roussy as the legal sponsor to prospectively collect real-world safety and activity data of innovative therapies administered to patients ≤ 25 years-old with pediatric malignancies (solid tumor or leukemia) or other related conditions, either on compassionate use of experimental drugs or off-label use of anti-cancer medicines that have been first approved in adults after 2007. Prior to SACHA inclusion, multicenter tumor board discussion defining best available therapeutic options for each patient with a relapsed malignancy is mandatory. Results: The SACHA study opened in March 2020 and by February 2022, 283 patients have been included from 29/31 SFCE recruiting centers; median age: 11.0 years (range: 0.3-24.4). Main cancer types were central nervous system (CNS) tumors (47%), followed by non-CNS tumors (40%) and leukemias (13%). Innovative therapies prescribed in &gt; 10 patients with reported objective response rate (ORR) and related CTCAE v.5 grade ≥2 clinical and/or grade ≥3 biological adverse drug reactions (ADRs) are described in Table. Conclusions: SACHA confirms the feasibility of this type of prospective real word registry, with a high participation of French centers. Based on this French experience, the Innovative Therapies for Children with Cancer (ITCC) consortium is currently developing a “SACHA International Project” to be opened in ITCC and collaborating countries. [Table: see text]

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

BackgroundThe 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.MethodFour 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.ResultsFour 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.ConclusionOur 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.

Perianal/perineal rhabdomyosarcoma: Results of the SIOP MMT 95, Italian RMS 96, and EpSSG RMS 2005 studies.

Rhabdomyosarcoma of the perianal/perineal region (PRMS) is rare, with poor survival and limited understanding of the functional consequences of treatment. International Society of Pediatric Oncology (SIOP) malignant mesenchymal tumor (MMT) 95, Italian RMS 96, and European paediatric Soft tissue sarcoma Study Group (EpSSG) RMS 2005 studies were interrogated to identify factors that impact survival; in RMS 2005, functional outcomes were analyzed. Fifty patients (nonmetastatic) were identified, median age 6.4years (range: 0.1-19.6): 29 male, 21 female. Tumors were >5cm in 33 patients. Histopathological subtype was alveolar in 35. Lymph nodes were involved in 23 patients. In RMS 2005, 16/21 (76%) tested alveolar tumors had positive FOXO1 fusion status. Diagnostic biopsy was performed in 37. Primary resection (13) was complete (R0) in one. Delayed primary excision (16) was complete in three. Radiotherapy (RT) in 34/50 patients included external beam (28), brachytherapy (3), and both (3). Nodal RT was given in 16/23 N1 patients (70%). Median follow-up of alive patients (29) was 84.1months (range: 3.6-221.1). Relapse or progression occurred in 24 patients (48%), 87% were fatal and most events (63%) were locoregional. Five-year event-free survival (EFS) was 47.8 (95% CI: 32.8-61.3), and 5-year overall survival (OS) was 52.6 (95% CI: 36.7-66.2), with age ≥10years and tumor size >5cm impacting 5-year EFS and OS (p<.05). Functional outcome data showed bowel, genito-urinary, and psychological issues; fecal incontinence in four of 21 survivors, and urinary symptoms in two of 21. About 60% of patients with nonmetastatic PRMS survive; older patients and those with large tumors have the worst outcomes. Biopsy should be the initial procedure, and definitive local therapy individualized. Quality-of-life and functional studies are needed to better understand the consequences of treatment.

Pathology of Wilms' tumour in International Society of Paediatric Oncology (SIOP) and Children's oncology group (COG) renal tumour studies: Similarities and differences

Excellent outcomes for patients with Wilms' tumour (WT), &gt;90% for all stages together, have been achieved through researching WT in multicentre and multinational trials and studies in the last 50 years, led by two major groups—the International Society of Paediatric Oncology (SIOP) and the Children's Oncology Group (COG) (previously the National Wilms' Tumour Study Group). Despite the two groups having different approaches, the survival outcomes are remarkably similar. In general, in the SIOP approach, which is followed in Europe and most other countries around the world, patients are first treated with preoperative chemotherapy; this is followed by surgery and, if necessary, postoperative chemotherapy and radiotherapy. In the COG approach, which is mainly followed in North America, patients are treated with upfront surgery, followed, if necessary, by postoperative chemotherapy and radiotherapy. In both groups, postoperative treatment primarily depends on tumour histological classification and stage, although, in recent studies, other prognostic factors have also been included (tumour volume, response to preoperative chemotherapy, and molecular markers). Owing to separate initial treatments, there are differences in histological assessment and subtyping of WT, and, more importantly, in staging criteria. In this review, we discuss the similarities and differences between the two groups in order to help pathologists who are dealing with WT to understand and follow the pathological protocol that is appropriate for a particular case, because, in many centres, both approaches may be followed, depending on individual case/patient circumstances.

Characteristics of white blood cell count in acute lymphoblastic leukemia: A COST LEGEND phenotype-genotype study.

White blood cell count (WBC) as a measure of extramedullary leukemic cell survival is a well-known prognostic factor in acute lymphoblastic leukemia (ALL), but its biology, including impact of host genome variants, is poorly understood. We included patients treated with the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-2008 protocol (N=2347, 72% were genotyped by Illumina Omni2.5exome-8-Bead chip) aged 1-45years, diagnosed with B-cell precursor (BCP-) or T-cell ALL (T-ALL) to investigate the variation in WBC. Spline functions of WBC were fitted correcting for association with age across ALL subgroups of immunophenotypes and karyotypes. The residuals between spline WBC and actual WBC were used to identify WBC-associated germline genetic variants in a genome-wide association study (GWAS) while adjusting for age and ALL subtype associations. We observed an overall inverse correlation between age and WBC, which was stronger for the selected patient subgroups of immunophenotype and karyotypes (ρBCP-ALL =-.17, ρT-ALL =-.19; p<3 × 10-4 ). Spline functions fitted to age, immunophenotype, and karyotype explained WBC variation better than age alone (ρ=.43, p<<2 × 10-6 ). However, when the spline-adjusted WBC residuals were used as phenotype, no GWAS significant associations were found. Based on available annotation, the top 50 genetic variants suggested effects on signal transduction, translation initiation, cell development, and proliferation. These results indicate that host genome variants do not strongly influence WBC across ALL subsets, and future studies of why some patients are more prone to hyperleukocytosis should be performed within specific ALL subsets that apply more complex analyses to capture potential germline variant interactions and impact on WBC.

Profile and Clinical Outcome of Children with Wilms' Tumor treated at a Tertiary Care Centre, India.

Pritanjali SinghBackground Wilms' tumor (WT) is the most common kidney tumor of the pediatric age group. The outcome of WT has improved due to the evolution of the treatment approach. A prospective observational study was conducted at All India Institute of Medical Sciences (AIIMS), Patna, to analyze the clinical profile along with the response and outcome to neoadjuvant chemotherapy according to the International Society of Pediatric Oncology (SIOP) protocol. Materials and Methods In total, 28 patients of WT visited the radiotherapy department from January 2015 to December 2019. Results Gender distribution showed male preponderance with a median age at diagnosis was 31 months. The abdominal lump was the dominant clinical presentation. The median volume of tumor at diagnosis was 359.48 mL (52.67-1805.76). Radiological staging workup shows that stage I, II, III, IV, and V were 7.1%, 39.3%, 39.3%, 10.7%, and 3.6% respectively. Neoadjuvant chemotherapy (NACT) was received by all patients. Also, 71.4% of patients showed > 50% of tumor volume reduction, while 28.6% of patients showed < 50% of tumor mass reduction. There was a statistically significant decrease in the tumor volume reduction following neoadjuvant chemotherapy ( p < 0.001). There was a statistically significant stage down ( p = 0.018) of the disease. Bivariate correlation studies showed recurrence was correlating statistically significantly with age < 24 months ( p = 0.049), locoregional lymph nodes ( p = 0.008), histopathological subtypes ( p < 0.001), stage of the disease ( p = 0.003), and risk groups ( p < 0.001). In addition, 25% of patients developed recurrence during the median follow-up of 25 months. The median disease-free survival (DFS) and overall survival (OS) were not reached. The mean DFS and OS were 48 and 59.13 months, respectively. One- and 3-year DFS were 100% and 64.1%, respectively. One- and 3-year OS were 100% and 75% respectively. Conclusion Our study suggests that most of the patients presented at an advanced stage, thus rendering most of the cases difficult to undergo surgery at presentation. Neoadjuvant chemotherapy followed by surgery may be considered a well-balanced approach with a comparable response and survival outcomes.

Multimodal Treatment of Nasopharyngeal Carcinoma in Children, Adolescents and Young Adults-Extended Follow-Up of the NPC-2003-GPOH Study Cohort and Patients of the Interim Cohort.

Simple SummaryMultimodal treatment of nasopharyngeal carcinoma (NPC) in children and young adults with induction chemotherapy, followed by radiochemotherapy and interferon-β (IFN-β) maintenance, has been successfully applied in studies NPC-91 and NPC-2003 of the German Society of Pediatric Oncology and Hematology (GPOH). We, here, present updated survival rates of the NPC-2003 study cohort after longer follow-up and include 21 additional patients recruited after closure of the study and treated as per the NPC-2003 study protocol (interim cohort) in our survival analysis. Survival rates remain high after extended follow-up and in the larger cohort with EFS and OS of 94% and 97%, respectively, reinforcing the high antitumor efficacy of this multimodal treatment concept. Seven patients with CR after induction therapy received a reduced radiation dose of 54 Gy, and none of them relapsed. Thus, the reduction of radiation dose seems feasible and has the potential to reduce treatment-related late effects in this vulnerable population.Nasopharyngeal carcinoma (NPC) in children and young adults has been treated within two consecutive prospective trials in Germany, the NPC-91 and the NPC-2003 study of the German Society of Pediatric Oncology and Hematology (GPOH). In these studies, multimodal treatment with induction chemotherapy, followed by radio (chemo)therapy and interferon-beta maintenance, yielded promising survival rates even after adapting total radiation doses to tumor response. The outcome of 45 patients in the NPC-2003 study was reassessed after a median follow-up of 85 months. In addition, we analyzed 21 further patients after closure of the NPC-2003 study, recruited between 2011 and 2017, and treated as per the NPC-2003 study protocol. The EFS and OS of 66 patients with locoregionally advanced NPC were 93.6% and 96.7%, respectively, after a median follow-up of 73 months. Seven patients with CR after induction therapy received a reduced radiation dose of 54 Gy; none relapsed. In young patients with advanced locoregional NPC, excellent long-term survival rates can be achieved by multimodal treatment, including interferon-beta. Radiation doses may be reduced in patients with complete remission after induction chemotherapy and may limit radiogenic late effects.

Current status of precision medicine in pediatric oncology in Spain: a consensus report by the Spanish Society of Paediatric Haematology and Oncology (SEHOP).

The study analyzes the current status of personalized medicine in pediatric oncology in Spain. It gathers national data on the tumor molecular studies and genomic sequencing carried out at diagnosis and at relapse, the centers that perform these studies, the technology used and the interpretation and clinical applicability of the results. Current challenges and future directions to achieve a coordinated national personalized medicine strategy in pediatric oncology are also discussed. Next generation sequencing-based (NGS) gene panels are the technology used in the majority of centers and financial limitations are the main reason for not incorporating these studies into routine care. Nowadays, the application of precision medicine in pediatric oncology is a reality in a great number of Spanish centers. However, its implementation is uneven and lacks standardization of protocols; therefore, national coordination to overcome the inequalities is required. Collaborative work within the Personalized Medicine Group of SEHOP is an adequate framework for encouraging a step forward in the effort to move precision medicine into the national healthcare system.