High‐dose treatment for malignant rhabdoid tumor of the kidney: No evidence for improved survival—The Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH) experience

1 Background

Malignant rhabdoid tumor of the kidney (MRTK) is the most aggressive childhood renal tumor with overall survival (OS) rates ranging from 22% to 42%. Whether high‐dose chemotherapy with autologous stem‐cell transplantation (HDSCT) in an intensive first‐line treatment offers additional benefit is an ongoing discussion.

2 Methods

A retrospective analysis of all 58 patients with MRTK from Austria, Switzerland, and Germany treated in the framework of consecutive, prospective renal/rhabdoid tumor studies SIOP9/GPO, SIOP93‐01/GPOH (where SIOP is International Society of Pediatric Oncology and GPOH is German Society of Pediatric Oncology and Hematology), SIOP2001/GPOH, and European Rhabdoid Tumor Registry from 1991 to 2014.

3 Results

Median age at diagnosis was 11 months. Fifty percent of patients had metastases or multifocal disease at diagnosis (Stage IV). Local stage distribution was as follows: not done/I/II/III—1/6/11/40. Fifteen (26%) patients underwent upfront surgery. Thirty‐seven (64%) patients achieved a complete remission, 17 (29%) relapsed, 34 (59%) died of disease progression, and two (3%) died of treatment‐related complication. Mean time to the first event was 3.5 months. Two‐year EFS/OS (where EFS is event‐free survival) for the whole group was 37 ± 6%/38 ± 6%. Metastases/multifocal disease, younger age, and local stage III were associated with significantly inferior survival. Eleven (19%) patients underwent HDSCT (carboplatin + thiotepa, n = 6; carboplatin + etoposide + melphalan, n = 4; others, n = 1); 2‐year OS in this group was 60 ± 15% compared to 34 ± 8% in the non‐HDSCT group (P = 0.064). However, the time needed from radiologic to histologic diagnosis, stem‐cell harvest, and HDSCT must also be taken into account to avoid selection bias by excluding the highest risk group with early progression (<90 days). Thus, 2‐year EFS only for patients without progression until day 90 was 60 ± 16% consolidated by HDSCT compared to 62 ± 11% without (P = 0.8).

4 Conclusion

Our retrospective analysis suggests comparable outcomes for patients with and without HDSCT, if adjusted for early disease progression.     

Facial deformation following treatment for pediatric head and neck rhabdomyosarcoma; the difference between treatment modalities. Results of a trans-Atlantic,multicenter cross-sectional cohort study

Background

The four different local therapy strategies used for head and neck rhabdomyosarcoma (HNRMS) include proton therapy (PT), photon therapy (RT), surgery with radiotherapy (Paris-method), and surgery with brachytherapy (AMORE). Local control and survival is comparable; however, the impact of these different treatments on facial deformation is still poorly understood. This study aims to quantify facial deformation and investigates the differences in facial deformation between treatment modalities.

Methods

Across four European and North American institutions, HNRMS survivors treated between 1990 and 2017, more than 2 years post treatment, had a 3D photograph taken. Using dense surface modeling, we computed facial signatures for each survivor to show facial deformation relative to 35 age–sex–ethnicity-matched controls. Additionally, we computed individual facial asymmetry.

Findings

A total of 173 HNRMS survivors were included, survivors showed significantly reduced facial growth (p < .001) compared to healthy controls. Partitioned by tumor site, there was reduced facial growth in survivors with nonparameningeal primaries (p = .002), and parameningeal primaries (p ≤.001), but not for orbital primaries (p = .080) All patients were significantly more asymmetric than healthy controls, independent of treatment modality (p ≤ .001). There was significantly more facial deformation in orbital patients when comparing RT to AMORE (p = .046). In survivors with a parameningeal tumor, there was significantly less facial deformation in PT when compared to RT (p = .009) and Paris-method (p = .007).

Interpretation

When selecting optimal treatment, musculoskeletal facial outcomes are an expected difference between treatment options. These anticipated differences are currently based on clinicians’ bias, expertise, and experience. These data supplement clinician judgment with an objective analysis highlighting the impact of patient age and tumor site between existing treatment options.     

Neurocognitive deficits may not resolve following pediatric kidney transplantation

Background

Pediatric chronic kidney disease (CKD) patients are at risk for cognitive deficits with worsening disease progression. Limited, existing cross-sectional studies suggest that cognitive deficits may improve following kidney transplantation. We sought to assess cognitive performance in relationship to kidney transplantation and kidney-specific medical variables in a sample of pediatric kidney transplant patients who provided cross-sectional and longitudinal observations.

Methods

A retrospective chart review was conducted in patients who completed pre- and/or post-transplant neurocognitive testing at the University of Iowa from 2015–2021. Cognitive outcomes were investigated with developmentally appropriate, standardized measures. Mixed linear models estimated the impact of transplant status on cognitive function (z-scores). Subsequent post-hoc t-tests on change scores were limited to patients who had provided pre- and post-transplant assessments.

Results

Thirty eight patients underwent cognitive assessments: 10 had both pre- and post-transplant cognitive assessments, 11 had pre-transplant assessments only, and 17 had post-transplant data only. Post-transplant status was associated with significantly lower full-scale IQ and slower processing speed compared to pre-transplant status (estimate = −0.32, 95% confidence interval [CI] = −0.52: −0.12; estimate = −0.86, CI = −1.17: −0.55, respectively). Post-hoc analyses confirmed results from the mixed models (FSIQ change score = −0.34, 95% CI = −0.56: −0.12; processing speed change score = −0.98, CI = −1.28: −0.68). Finally, being ≥80 months old at transplant was associated with substantially lower FSIQ compared to being <80 months (estimate = −1.25, 95% CI = −1.94: −0.56).

Conclusions

Our results highlight the importance of monitoring cognitive function following pediatric kidney transplant and identify older transplant age as a risk factor for cognitive deficits.     

Outcome of patients with undifferentiated embryonal sarcoma of the liver treated according to European soft tissue sarcoma protocols

Background

To assess the outcomes of pediatric patients with undifferentiated embryonal sarcoma of the liver (UESL) and treatment including at least surgery and systemic chemotherapy.

Methods

This study included patients aged up to 21 years with a pathological diagnosis of UESL prospectively enrolled from 1995 to 2016 in three European trials focusing on the effects of surgical margins, preoperative chemotherapy, use of radiotherapy (RT), and chemotherapy.

Results

Out of 65 patients with a median age at diagnosis of 8.7 years (0.6–20.8), 15 had T2 tumors, and one had lymph node spread, 14 were Intergroup Rhabdomyosarcoma Study (IRS) I, nine IRS II, 38 IRS III, and four IRS IV. Twenty-eight upfront surgeries resulted in five operative spillages and 11 infiltrated surgical margins, whereas 37 delayed surgeries resulted in no spillages (p = .0119) and three infiltrated margins (p = .0238). All patients received chemotherapy, including anthracyclines in 47. RT was administered in 15 patients. With a median follow-up of 78.6 months, 5-year overall and event-free survivals (EFS) were 90.1% (95% confidence interval [CI]: 79.2–95.5) and 89.1% (95% CI: 78.4–94.6), respectively. Two out four local relapses had previous infiltrated margins and two out of three patients with metastatic relapses received reduced doses of alkylating agents. Infiltrated margins (p = .1607), T2 stage (p = .3870), use of RT (p = .8731), and anthracycline-based chemotherapy (p = .1181) were not correlated with EFS.

Conclusions

Multimodal therapy improved the outcome of UESL. Neoadjuvant chemotherapy for pediatric patients increases the probability of complete surgical resection. The role of anthracyclines and RT for localized disease remains unclear.     

Localized vaginal/uterine rhabdomyosarcoma—results of a pooled analysis from four international cooperative groups

1 Background

Vaginal/uterine rhabdomyosarcoma (VU RMS) is one of the most favorable RMS sites. To determine the optimal therapy, the experience of four cooperative groups (Children's Oncology Group [COG], International Society of Pediatric Oncology (SIOP) Malignant Mesenchymal Tumor Group [MMT], Italian Cooperative Soft Tissue Sarcoma Group [ICG], and European pediatric Soft tissue sarcoma Study Group [EpSSG]) was analyzed.

2 Procedure

From 1981 to 2009, 237 patients were identified. Median age (years) at diagnosis differed by tumor location; it was 1.9 for vagina (n = 160), 2.7 for uterus corpus (n = 26), and 13.5 for uterus cervix (n = 51). Twenty‐eight percent of patients received radiation therapy (RT) as part of primary therapy (23% COG, 27% MMT, 46% ICG, and 42% EpSSG), with significant differences in the use of brachytherapy between the cooperative groups (23% COG, 76% MMT, 64% ICG, and 88% EpSSG).

3 Results

Ten‐year event‐free (EFS) and overall survival (OS) were 74% (95% CI, 67–79%) and 92% (95% CI, 88–96%), respectively. In univariate analysis, OS was inferior for patients with uterine RMS and for those with regional lymph node involvement. Although EFS was slightly lower in patients without initial RT (71% without RT vs. 81% with RT; P = 0.08), there was no difference in OS (94% without RT vs. 89% with RT; P = 0.18). Local control using brachytherapy was excellent (93%). Fifty‐one (51.5%) of the 99 survivors with known primary therapy and treatment for relapse were cured with chemotherapy with or without conservative surgery.

4 Conclusions

About half of all patients with VU RMS can be cured without systematic RT or radical surgery. When RT is indicated, modalities that limit sequelae should be considered, such as brachytherapy.     

The changing clinical pattern of endemic Burkitt lymphoma in Western Africa: Experience from a tertiary center in Ghana

1 Background

Burkitt lymphoma (BL) is the most common childhood cancer in Ghana, where the endemic variant is the predominant subtype and historically presents as a highly chemo‐sensitive jaw tumor. This study aimed to update the current epidemiological characteristics of childhood BL in our institution.

2 Procedure

Patient data for all children diagnosed with BL and seen at Korle Bu Teaching Hospital between January 2007 and December 2012 were retrospectively analyzed.

3 Results

BL was diagnosed in 173 children (<13 years) during the study period, with the abdomen as the most common tumor site (46%) followed by the jaw (31%). Abdominal tumors were associated with advanced/disseminated disease (P = 0.002), and were more likely to occur in females irrespective of tumor stage (relative risk = 1.56 [95% CI; 1.1–12.3]). Twenty‐five percent (43/173) of the study cohort died and mortality was influenced by increasing age (P = 0.02) and advanced disease (P = 0.03). Treatment delay was experienced by nine in ten patients primarily due to familial financial constraint (75%). Treatment abandonment was observed as a first event in 94% of patients and two thirds of children in the study were eventually lost to follow‐up.

4 Conclusion

The predominance of primary abdominal tumors in our study cohort may indicate a changing epidemiological pattern of BL in Ghana. High rates of treatment delay and abandonment were evident and are likely to be contributing factors to the poor childhood cancer survival outcomes seen in resource‐limited countries in Africa.     

Dose‐escalation is needed for gross disease in high‐risk neuroblastoma

1 Background

Locoregional failure is common after subtotal resection in high‐risk neuroblastoma. Although a dose of 21 Gy radiation therapy (RT) is standard for treatment of high‐risk neuroblastoma after gross total resection, the dose needed for local control of patients with gross residual disease at the time of RT is unknown. We sought to evaluate local control after 21–36 Gy RT in patients with high‐risk neuroblastoma undergoing subtotal resection.

2 Methods

All patients with high‐risk neuroblastoma who received RT to their primary site from 2000 to 2016 were reviewed. Of the 331 patients who received consolidative RT to their primary site, 19 (5.7%) underwent subtotal resection and were included in our analysis. Local failure (LF) was correlated with biologic prognostic factors and dose of RT.

3 Results

Median follow‐up among surviving patients was 6.0 years. Median RT dose was 25 Gy (range, 21 Gy–36 Gy). The 5‐year cumulative incidence of LF among all patients was 17.2%. LF at 5 years was 30% in those who received <30 Gy versus 0% in those who received 30–36 Gy (P = 0.12). There was a trend towards improved local control in patients with tumor size ≤10 cm at diagnosis (P = 0.12). The 5‐year event‐free and overall survival were 44.9% and 68.7%, respectively.

4 Conclusion

After subtotal resection, patients who received less than 30 Gy had poor local control. Doses of 30–36 Gy are likely needed for optimal control of gross residual disease at the time of consolidative RT in high‐risk neuroblastoma.     

Treatment‐related mortality in relapsed childhood acute lymphoblastic leukemia

1 Background

Treatment of relapsed childhood acute lymphoblastic leukemia (ALL) is particularly challenging due to the high treatment intensity needed to induce and sustain a second remission. To improve results, it is important to understand how treatment‐related toxicity impacts survival.

2 Procedure

In this retrospective population‐based study, we described the causes of death and estimated the risk for treatment‐related mortality in patients with first relapse of childhood ALL in the Nordic Society of Paediatric Haematology and Oncology ALL‐92 and ALL‐2000 trials.

3 Results

Among the 483 patients who received relapse treatment with curative intent, we identified 52 patients (10.8%) who died of treatment‐related causes. Twelve of these died before achieving second remission and 40 died in second remission. Infections were the cause of death in 38 patients (73.1%), predominantly bacterial infections during the chemotherapy phases of the relapse treatment. Viral infections were more common following hematopoietic stem cell transplantation (HSCT) in second remission. Independent risk factors for treatment‐related mortality were as follows: high‐risk stratification at relapse (hazard ratio [HR] 2.2; 95% confidence interval [CI] 1.3–3.9; P < 0.01), unfavorable cytogenetic aberrations (HR 3.4; 95% CI 1.3–9.2; P = 0.01), and HSCT (HR 4.64; 95% CI 2.17–9.92; P < 0.001). In contrast to previous findings, we did not observe any statistically significant sex or age differences. Interestingly, none of the 17 patients with Down syndrome died of treatment‐related causes.

4 Conclusions

Fatal treatment complications contribute significantly to the poor overall survival after relapse. Implementation of novel therapies with reduced toxicity and aggressive supportive care management are important to improve survival in relapsed childhood ALL.     

Socioeconomic status significantly impacts childhood cancer survival in South Africa

Background and aims

Significantly discrepant survival rates have been documented in single disease childhood cancer cohorts in South Africa; those from higher socioeconomic groups were shown to have a significantly lower risk of death than those from less affluent households. This study aimed to determine the impact of socioeconomic status (SES) on childhood cancer survival using pooled South African data.

Methods

Five databases spanning January 2000 to December 2021 were interrogated. SES status was assigned based on a public sector annual household income classification. H0 households (formally unemployed) received free healthcare. H1, H2 and H3 (annual income > United States Dollar [USD] 19,000) households paid for healthcare relative to their income. The Spearman test assessed correlations between SES and disease stage in patients with solid tumours. Hazard ratios were determined using Cox regression modelling. The Kaplan–Meier procedure estimated overall survival (OS).

Results

A total of 1598 children were eligible for analysis; 1269 had a solid tumour with a negative correlation between SES and stage (Spearman rho = −.178; p < .001). Patients with solid tumours and lower SES showed proportionately higher numbers of stage III and IV disease (p < .01). This proportion decreased with higher SES categories. In the multivariate analyses adjusted for sex, age, tumour type and stage, higher SES was associated with lower mortality risk (p < .001), indicating that the impact of SES on survival was in excess of any effect that could be explained by lower stage disease alone. There was a strong positive correlation between race and SES (Fisher's exact tests, p < .001) across all groups and all SES strata. Five-year OS was 85.3% in children from H3 households versus 46.3% in children from H0 households (p < .001).

Conclusion

SES significantly impacts childhood cancer survival for children with solid tumours in South Africa. SES is a robust surrogate for race in South Africa as a prognostic metric of disease outcome in childhood cancer. Advocacy to increase social support for impoverished patients is essential to achieve equitable improvements in outcomes treated with standardised national treatment guidelines.     

Impact of ovarian transposition before pelvic irradiation on ovarian function among long‐term survivors of childhood Hodgkin lymphoma: A report from the St. Jude Lifetime Cohort Study

1 Background

We reviewed the effect of ovarian transposition (OT) on ovarian function among long‐term survivors of childhood Hodgkin lymphoma (HL) treated with pelvic radiotherapy.

2 Procedure

Female participants (age 18+ years) with HL in the St. Jude Lifetime Cohort Study (SJLIFE) were clinically evaluated for premature ovarian insufficiency (POI) 10 or more years after pelvic radiotherapy. Reproductive history including age at menopause and pregnancy/live births was available on all patients.

3 Results

Of 127 eligible females with HL, 90 (80%) participated in SJLIFE, including 49 who underwent OT before pelvic radiotherapy. Median age at STLIFE evaluation was 38 years (range 25–60). In a multiple regression adjusted for age at diagnosis, pelvic radiotherapy doses > 1,500 cGy (hazard ratio [HR] = 25.2, 95% confidence interval [CI] = 3.1–207.3; P = 0.0027) and cumulative cyclophosphamide equivalent doses of alkylating agents > 12,000 mg/m² (HR = 11.2, 95% CI = 3.4–36.8; P < 0.0001) were significantly associated with POI. There was no significant association between OT and occurrence of POI (HR = 0.6, 95% CI = 0.2–1.9; P = 0.41).

4 Conclusions

OT did not appear to modify risk of POI in this historic cohort of long‐term survivors of HL treated with gonadotoxic therapy. Modern fertility preservation modalities, such as mature oocyte cryopreservation, should be offered to at‐risk patients whenever feasible.     

Single kidney and ureteral atresia in a newborn girl: a treatment concept

Objective

To demonstrate a rare case of urological pathology, we report a combination of a single kidney and ureteral atresia. The treatment concept and outcome are outlined.

Patient and method

Antenatal ultrasound had revealed urinary ascites which lead to caesarean section in the 34th gestational week. Persisting anuria was confirmed postnatally and peritoneal dialysis started on the second day of life. Subsequent laparotomy revealed ureteral atresia after 3 cm of patent ureter. We created an ileum conduit after discussing various other therapeutic options.

Result and conclusion

A follow up of 12 months has shown steady function of the stoma with stable renal parameters. An ileal conduit represents a good option if high drainage is necessary in early childhood.     

Determining the prevalence of vestibular screening failures in pediatric cancer patients whose therapies include radiation to the head/neck and platin‐based therapies: A pilot study

1 Background

Sensorineural hearing loss due to ototoxic cancer therapy is well established; effects on the vestibular system are unknown. We examined the feasibility of implementing vestibular screens for pediatric cancer survivors exposed to ototoxic agents. The prevalence of screening failures is reported.

2 Methods

Cancer survivors who were 6–17 years, at least 1‐month posttreatment, and received ototoxic therapy (radiation to the head/neck, cisplatin, carboplatin) were eligible. Screening measures included (1) Pediatric Vestibular Symptom Questionnaire, (2) Modified Clinical Test of Sensory Interaction on Balance, and (3) Dynamic Visual Acuity.

3 Results

Vestibular screening failures were observed in 30 participants (60%). Patients with a brain tumor diagnosis were at increased risk for failures compared to nonbrain tumor patients (74.2% vs. 36.8%, P = 0.009). Patients who underwent brain surgery were at increased risk for failures compared to patients without brain surgery (71% vs. 42%, P = 0.043). Patients with a longer duration between end of treatment and vestibular screening had a reduced risk of failures, with an almost 20% decrease for each year between the time points (odds ratio = 0.812; 95% confidence interval: 0.683–0.964, P = 0.018). Receiving carboplatin correlated with a decreased risk of failure (P = 0.016), due to a negative correlation with other clinical risk factors (diagnosis of a brain tumor, major brain surgery) that are associated with vestibular screening failure.

4 Conclusion

Vestibular screening failures are highly prevalent in childhood cancer survivors who received ototoxic therapy. Broad screening of this population and further characterization of these patients are warranted.     

Post-operative flank irradiation using conformal versus highly conformal radiotherapy techniques for paediatric renal tumours: Results from the French registry PediaRT

Purpose

Three-dimensional conformal RT (3D-RT) techniques are gold standard for post-operative flank radiotherapy (RT) in paediatric renal tumours. Recently, highly conformal RT (HC-RT) techniques have been implemented without comparative clinical data. The main objective of this multicentre study was to compare locoregional control (LRC) in children treated either with HC-RT or 3D-RT techniques.

Methods

Patients treated with post-operative flank RT for renal tumour registered in the national cohort PediaRT between March 2013 and September 2019 were included. Treatment and follow-up data, including toxicities and outcomes, were retrieved from the database. LRC was calculated, and dose reconstruction was performed in case of an event.

Results

Seventy-nine patients were included. Forty patients were treated with HC-RT and 39 with 3D-RT. Median follow-up was 4.5 years. Three patients had locoregional failure (LRF; 4%). HC-RT was not associated with a higher risk of LRF. Three-year LRC were 97.4% and 94.7% in the HC-RT and 3D-RT groups, respectively. The proportion of planning target volumes receiving 95% or more of the prescribed dose did not significantly differ between both groups (HC-RT 88%; 3D-RT 69%; p = .05). HC-RT was better achieving dose constraints, and a significant mean dose reduction was observed in the peritoneal cavity and pancreas associated with lower incidence of acute gastrointestinal toxicity.

Conclusion

LRF after post-operative flank RT for renal tumours was rare and did not increase using HC-RT versus 3D-RT techniques. Dose to the pancreas and the peritoneal cavity, as well as acute toxicity, were reduced with HC-RT compared to 3D-RT.     

Management of cryptorchidism: a survey of clinical practice in Italy

Background  

An evidence-based Consensus on the treatment of undescended testis (UT) was recently published, recommending to perform orchidopexy between 6 and 12 months of age, or upon diagnosis and to avoid the use of hormones. In Italy, current practices on UT management are little known. Our aim was to describe the current management of UT in a cohort of Italian children in comparison with the Consensus guidelines. As management of retractile testis (RT) differs, RT cases were described separately.     

Nephrolithiasis in pediatric hematopoietic cell transplantation with up to 40 years of follow‐up

Background

Kidney stones have been reported to occur after childhood cancer, but little is known about kidney stones in children following hematopoietic cell transplantation (HCT). The objective of this retrospective study was to determine risk factors for the development of kidney stones and to describe the prevalence among survivors.

Procedure

The study included 1,343 childhood HCT patients. Mean follow‐up was 15.8 (1.0–40.0) years. Patients were treated with total body irradiation (TBI) (n = 948) or non‐TBI regimens. Methotrexate (MTX) for acute graft‐versus‐host disease (GVHD) prophylaxis was given as long‐course (n = 360), short‐course (n = 626), or none (n = 357). Prednisone for chronic GVHD therapy was received by 525 patients. Multivariate Cox regression models were used to estimate the hazard ratio (HR) of risk factors associated with kidney stones.

Results

Kidney stones developed in 51 patients, a median of 9.9 (0.2–29.4) years after first HCT, with a 30‐year cumulative incidence of 7.4%. Risk factors associated with kidney stones were TBI (HR = 2.2; P = 0.03), age at HCT (12–18 vs. <6 years, HR = 2.7; P = 0.01), MTX (long vs. none, HR = 3.6; P = 0.02), and prednisone (HR = 2.2; P = 0.008). Among 868 survivors, the prevalence of a history of kidney stones was 4.7%.

Conclusions

Survivors of childhood HCT have an increased risk of developing kidney stones. Pediatr Blood Cancer 2014;61:417–423. © 2013 Wiley Periodicals, Inc.     

Evaluation of bowel function in healthy children: untreated constipation is common

Aim

We evaluated bowel function in healthy children with regard to gender and age.

Methods

The study was carried out in 2016 at a tertiary children's hospital. Healthy children aged 3.5 years to 15 years who were admitted to the hospital, siblings to patients or offspring of staff members were included. Validated self‐report questionnaires and internally developed questions regarding obstructive outlet‐ and gas‐related symptoms were used.

Results

A total of 310 participants (50% girls) were included, which corresponded to a 94% answer frequency. Respondents were divided into a younger age group (3.5 years to seven years), consisting of 135 children, and an older age group (eight years to 15 years), consisting of 175 children. Younger children reported more foul odours than older children (50% vs. 29%, p = 0.001) and more obstructive symptoms (21% vs. 10%, p = 0.01). There was no difference between the age groups regarding constipation (19% vs 16%, NS). Overall, 55% of those with constipation had no treatment for the condition, although they reported abdominal pain (51%) and problems with foul odours (57%).

Conclusion

Healthy children frequently reported constipation, abdominal pain and gas‐related problems, but treatment was rare. Overall, bowel function seemed to improve during childhood, although constipation remained largely untreated.     

A twin study exploring the association between childhood emotional and behaviour problems and specific psychotic experiences in a community sample of adolescents

Background

Childhood emotional and behaviour problems are antecedents for later psychopathology. This study investigated genetic and environmental influences shaping the longitudinal association between childhood emotional and behaviour problems and specific PEs.

Method

In a community‐based twin sample, parents reported on emotional and behaviour problems when twins were ages 7 and 12 years. At age 16 years, specific PEs were measured using self‐reports and parent reports. Structural equation model‐fitting was conducted.

Results

Childhood emotional and behaviour problems were significantly associated with paranoia, cognitive disorganisation and parent‐rated negative symptoms in adolescence (mean r = .15–.38), and to a lesser extent with hallucinations, grandiosity and anhedonia (mean r = .04‐.12). Genetic influences on childhood emotional and behaviour problems explained significant proportions of variance in adolescent paranoia (4%), cognitive disorganisation (8%) and parent‐rated negative symptoms (3%). Unique environmental influences on childhood emotional and behaviour problems explained ≤1% of variance in PEs. Common environmental influences were only relevant for the relationship between childhood emotional and behaviour problems and parent‐rated negative symptoms (explaining 28% of variance) and are partly due to correlated rater effects.

Conclusions

Childhood emotional and behaviour problems are significantly, if weakly, associated with adolescent PEs. These associations are driven in part by common genetic influences underlying both emotional and behaviour problems and PEs. However, psychotic experiences in adolescence are largely influenced by genetic and environmental factors that are independent of general childhood emotional and behaviour problems, suggesting they are not merely an extension of childhood emotional and behaviour problems.     

Childhood T-lineage acute lymphoblastic leukemia: Management and outcome at a tertiary care center in North India

Objective  

To assess the clinical features, prognostic factors and outcome of childhood T-ALL in comparison with B-lineage ALL, treated with a uniform treatment regimen (MCP 841).     

Efficacy of non-pharmacological interventions to reduce pain in children with sickle cell disease: A systematic review

Background

Pain is the clinical hallmark of sickle cell disease (SCD) leading to hospitalization, psychological sequelae and a decreased health-related quality of life. The aim of this systematic literature review is to evaluate the efficacy of non-pharmacological interventions in reducing sickle cell related pain in children with SCD.

Methods

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a comprehensive literature search up until October 2022 was performed to identify studies that investigated the efficacy of non-pharmacological interventions on (1) pain frequency and/or intensity, and (2) analgesic and health service use in children with SCD until the age of 21. Both randomized controlled trials (RCTs) and quasi-experimental designed (QED) studies were considered for inclusion.

Results

Ten articles (five RCTs and five QED studies) with 422 participants were included. They investigated cognitive behavioural therapy (CBT) (n = 5), biofeedback (n = 2), massage (n = 1), virtual reality (n = 1) and yoga (n = 1). The majority of the interventions were psychological (n = 7) and were performed in the outpatient clinic (n = 6). CBT and biofeedback significantly reduced frequency and/or intensity of SCD-related pain in outpatient settings, while virtual reality and yoga significantly reduced pain in inpatient settings. Biofeedback also significantly reduced analgesic use. None of the included articles reported reduced health service use.

Conclusion

Non-pharmacological interventions may be effective in reducing pain in paediatric patients with SCD. However, due to the heterogeneity of the included studies a quantitative analysis could not be performed. Awaiting further supporting evidence, healthcare providers should consider implementing these interventions as valuable part of a comprehensive pain management strategy plan.     

Wilms tumor treatment protocol compliance and the influence on outcomes for children in Tanzania

Background

Standardized Wilms tumor treatment protocols exist for low- and middle-income countries, but outcomes equivalent to high-income countries are not achieved outside of clinical trials. As Wilms tumor treatment protocols in Africa shift with increasing resource capacity, it is not known how treatment compliance to each stage of therapy affects outcomes and where the critical breakpoints are for protocol adherence in clinical practice.

Procedure

We describe both treatment outcomes and treatment protocol adherence in a retrospective single-center cohort study of pediatric Wilms tumor patients at a zonal cancer referral hospital in Tanzania from 2016 to 2019, treated per the International Society of Paediatric Oncology standard (2016–2017) or Tanzania adapted (2018–2019) therapy protocols.

Results

A total of 69 patients were evaluated. The two-year overall survival and event-free survival rates were 40% and 29%, respectively. Only 29% of patients completed recommended chemotherapy per protocol, and completion of preoperative and postoperative chemotherapy was predictive of two-year overall survival (odds ratio [OR] 14.4, p < .001). There were delays at almost every stage of treatment, especially time from preoperative chemotherapy to surgery (56 days), from surgery to pathology report (30 days), and from surgery to initiation of postoperative chemotherapy (38 days).

Conclusions

Nonadherence with recommended Wilms tumor treatment guidelines due to key health system delays correlated to reduced overall survival rates, with chemotherapy nonadherence due to abandonment, lack of surgery, and deaths on therapy as the strongest contributors. Future interventions targeting health system delays and reducing deaths during therapy are critical to improving protocol compliance and increasing overall survival for pediatric Wilms tumor patients in low-resource settings.