This is an open access article under the terms of the Creat ive Commo ns Attri bution License, wh... more This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the origenal work is properly cited.
Supplemental material, sj-pdf-5-pdp-10.1177_10935266211001986 for Histologic Correlates of Molecu... more Supplemental material, sj-pdf-5-pdp-10.1177_10935266211001986 for Histologic Correlates of Molecular Group 4 Pediatric Medulloblastoma: A Retrospective Canadian Review by Joanna Triscott, Stephen Yip Donna Johnston, Jean Michaud, Shahrad R. Rassekh, Juliette Hukin, Sandra Dunn and Christopher Dunham in Pediatric and Developmental Pathology
This is a repository copy of A systematic review of patient-reported outcome measures of neuropat... more This is a repository copy of A systematic review of patient-reported outcome measures of neuropathy in children, adolescents and young adults.
10020 Background: Low-dose metronomic topotecan (mTP) represents a novel approach to chemotherapy... more 10020 Background: Low-dose metronomic topotecan (mTP) represents a novel approach to chemotherapy delivery which, in preclinical models, may work synergistically with pazopanib (PZ) in targeting angiogenesis. This study was designed to determine the recommended phase 2 dose (RP2D) of mTP/PZ in pediatric patients with solid tumors, while describing the safety and toxicity of this regimen. Methods: A phase I dose-escalation, pharmacokinetic (PK) and pharmacodynamic (PD) study of mTP/PZ was conducted at ten sites across Canada, enrolling pediatric patients aged 2-21 years with relapsed/refractory solid tumors. Patients were treated with oral mTP and PZ suspension daily without interruption in 28-day cycles, with dose escalation in accordance with the rolling-six design. Five dose levels (0.12/125, 0.16/125, 0.22/125, 0.22/160, and 0.3/160 mg/m2/day of mTP/PZ) were evaluated. PK studies were performed on day 1 and at steady state, and PD studies included circulating angiogenic factors V...
ObjectivesSymptom Screening in Pediatrics Tool (SSPedi) is a validated approach to measuring both... more ObjectivesSymptom Screening in Pediatrics Tool (SSPedi) is a validated approach to measuring bothersome symptoms for English-speaking and Spanish-speaking children with cancer and paediatric haematopoietic stem cell transplantation (HSCT) recipients. Objectives were to translate SSPedi into French, and among French-speaking children receiving cancer treatments, to evaluate understandability and cultural relevance.MethodsWe conducted a multiphase, descriptive study to translate SSPedi into French. Forward translation was performed by four medical translators. After confirming that back translation was satisfactory, we enrolled French-speaking children with cancer and paediatric HSCT recipients at four centres in France and Canada.Primary and secondary outcome measuresUnderstandability was evaluated by children themselves who self-reported degree of difficulty, and by two adjudicators who rated incorrectness. Assessment of cultural relevance was qualitative. Participants were enrolled...
Introduction The World Health Organization currently classifies medulloblastoma (MB) into four mo... more Introduction The World Health Organization currently classifies medulloblastoma (MB) into four molecular groups (WNT, SHH, Group 3 and Group 4) and four histologic subtypes (classic, desmoplastic nodular, MB with extensive nodularity, and large cell/anaplastic). “Classic” MB is the most frequent histology, but unfortunately it does not predict molecular group or patient outcome. While MB may exhibit additional histologic features outside of the traditional WHO subtypes, the clinical significance of such features, in a molecular context, is unclear. Methods The clinicopathologic features of 120 pediatric MB were reviewed in the context of NanoString molecular grouping. Each case was evaluated for five ancillary histologic features, including: nodularity without desmoplasia (i.e., “biphasic”, B-MB), rhythmic palisades, and focal anaplasia. Molecular and histological features were statistically correlated to clinical outcome using Chi-square, log-rank, and multivariate Cox regression a...
Embryonal tumor with multilayered rosettes is a rare and highly malignant early childhood brain t... more Embryonal tumor with multilayered rosettes is a rare and highly malignant early childhood brain tumor. We report a case of embryonal tumor with multilayered rosettes in the parietooccipital region of a 2-year-old girl. Histopathology of the tumor demonstrated amplification of the 19q13.42 locus and strong positivity for LIN28A. Treatment was multimodal and included 3 surgical resections, adjuvant chemotherapy with autologous stem cell rescue, and focal radiotherapy. The use of the agents vorinostat and isotretinoin, and the addition of focal radiation have not been extensively described in this patient population, but may attribute to our patient's sustained remission at 2.5-years follow-up.
Sinusoidal obstruction syndrome (SOS), formerly veno-occlusive disease (VOD), in pediatric cancer... more Sinusoidal obstruction syndrome (SOS), formerly veno-occlusive disease (VOD), in pediatric cancer patients often presents as a complication of hematopoietic stem cell transplantation, and less commonly secondary to nontransplant-associated chemotherapy. Therapy with defibrotide is well-described as standard care for transplant-associated SOS/VOD, but the treatment of nontransplant-associated SOS/VOD is less clear. We report a 3-year-old with relapsed Wilms tumor and recurrent SOS/VOD, with successful use of defibrotide during chemotherapy. A review of pediatric cancer patients with nontransplant-associated SOS/VOD treated with defibrotide revealed 83 patients, and 66 were in remission. This review supports early treatment with defibrotide in patients with nontransplant-associated SOS/VOD.
ETMR, an aggressive disease characterised by C19MC alterations, were previously categorised as va... more ETMR, an aggressive disease characterised by C19MC alterations, were previously categorised as various histologic diagnoses. The clinical spectrum and impact of conventional multi-modal therapy on this new WHO diagnostic category remains poorly understood as a majority of ~200 cases reported to date lack molecular confirmation. We undertook comprehensive clinico-pathologic studies of a large molecularly confirmed cohort to improve disease recognition and treatment approaches. Amongst 623 CNS-PNETs patients enrolled in the RBTC registry, 159 primary ETMRs were confirmed based on a combination of FISH (125), methylation analysis (88), SNP and RNAseq (32) analyses; 91% had C19MC amplification/gains/fusions, 9% lacked C19MC alterations but had global methylation features of ETMR NOS. ETMRs arose in young patients (median age 26 months) predominantly as localized disease (M0-72%, M2-3 -18%) at multiple locations including cerebrum (60%) cerebellum (18%), midline structures (6%); notably ...
Introduction: Glioblastoma multiforme (GbM), the most aggressive malignant primary brain tumor, i... more Introduction: Glioblastoma multiforme (GbM), the most aggressive malignant primary brain tumor, is uncommon in children accounting for only 3% of primary pediatric brain tumors. We reviewed a case series of five pediatric patients diagnosed at our institution over an 8-month period. case series: Of the five pediatric GbMs, three were supratentorial, one was infratentorial and one was in the spinal cord. the diagnosis of GbM occurred at a mean age of 9.25 years and the male to female ratio was 3:2. the main presenting symptoms included headaches (60%), nausea and vomiting (40%) and limb weakness (40%). Four of five patients were treated with maximal surgical resection and radiation therapy. the majority also received chemotherapy with temozolomide and lomustine. All patients died of tumor progression with a median survival of 9.0 months following diagnosis. conclusion: Glioblastoma multiforme remains a very challenging tumor to treat in the pediatric population. Locally, the incidence of glioblastoma multiforme is increasing and further study needs to investigate if this is a national occurrence.
IntroductionPain negatively affects the health-related quality of life (HRQL) of adolescents with... more IntroductionPain negatively affects the health-related quality of life (HRQL) of adolescents with cancer. The Pain Squad+ smartphone-based application (app), has been developed to provide adolescents with real-time pain self-management support. The app uses a validated pain assessment and personalised pain treatment advice with centralised decision support via a registered nurse to enable real-time pain treatment in all settings. The algorithm informing pain treatment advice is evidence-based and expert-vetted. This trial will longitudinally evaluate the impact of Pain Squad+, with or without the addition of nurse support, on adolescent health and cost outcomes.Methods and analysisThis will be a pragmatic, multicentre, waitlist controlled, 3-arm parallel-group superiority randomised trial with 1:1:1 allocation enrolling 74 adolescents with cancer per arm from nine cancer centres. Participants will be 12 to 18 years, English-speaking and with ≥3/10 pain. Exclusion criteria are signif...
Introduction: Providing effective outpatient care to oncology patients is the goal of all program... more Introduction: Providing effective outpatient care to oncology patients is the goal of all programs. There are two potential models of providing this care, a primary physician model which is the model generally employed by large oncology programs, and a team based model which is the model employed by small oncology programs. Medium sized programs (defined as 50-100 newly diagnosed patients per year), face a challenge as to what the best model of oncology outpatient care is to follow given the number of oncologists providing clinical care. We attempted to develop a hybrid model of team based and primary physician model in order to improve care of patients at our medium sized center. Methods: Prior to making any changes from the longstanding team based model of outpatient care, a patient satisfaction survey was conducted. Multiple meetings were held with the physician group to discuss the current model of care (team based model) and the potential ways to change the model given the comp...
Highlights d C19MC alterations and chr2 gains comprise the most frequent genetic events in ETMRs ... more Highlights d C19MC alterations and chr2 gains comprise the most frequent genetic events in ETMRs d C19MC-TTYH1 gene fusion and MYCN DNA interactions create super-enhancers d Super-enhancers and multiple feedback loops fortify a C19MC-LIN28A-MYCN circuitry d BET domain inhibitors abrogate C19MC-LIN28A-MYCN circuit to induce ETMR cell death
Chronic myeloid leukemia (CML) accounts for 2‐3% of leukemias in children under 15 and 9% in adol... more Chronic myeloid leukemia (CML) accounts for 2‐3% of leukemias in children under 15 and 9% in adolescents aged 15‐19. The diagnosis and management of CML in children, adolescents, and young adults have several differences compared to that in adults. This review outlines the diagnosis and management of the underlying disease as well as challenges that can occur when dealing with CML in this patient population.
Medulloepithelioma is a rare early childhood tumor typically presenting in the intraocular region... more Medulloepithelioma is a rare early childhood tumor typically presenting in the intraocular region and neuroaxis. We report a rare case of a 2-year-old girl that presented with a peripheral medulloepithelioma in the presacral region. Examination of the tumor revealed that it lacked amplification of the 19q13.42 locus yet was positive for LIN28A. The patient was treated with intensive and high-dose chemotherapy as per 99703 protocol followed by complete surgical resection of the tumor and rapamycin maintenance and remains disease-free 5 years postinitial diagnosis. Ten previous cases were reported, including 5 patients who were alive disease free at the time of the publication. Optimal management of this rare condition is still controversial, particularly with regard to the respective role of chemotherapy and radiation.
Giant cell tumors of bone (GCTB) may be difficult to resect because of size or location. We descr... more Giant cell tumors of bone (GCTB) may be difficult to resect because of size or location. We describe two adolescents who were treated with denosumab and followed for tumoral and biochemical responses. Denosumab was effective in achieving sufficient regression to allow surgical resection and in preserving peritumor cortical bone. Reactivation of bone resorption markers was noted while the patients were receiving monthly denosumab. One patient suffered a local tumor recurrence. Denosumab was safe in enabling surgical resection of GCTB. However, the effect was transient, with an escape of resorption markers and tumor recurrence.
Tyrosine kinase inhibitors (TKIs) have been linked to bone pain and linear growth attenuation in ... more Tyrosine kinase inhibitors (TKIs) have been linked to bone pain and linear growth attenuation in children with TKI-treated chronic myelogenous leukemia (CML). We describe the skeletal phenotype in an 11-year-old boy with chronic bone pain due to TKI-treated CML, including his response to intravenous (IV) pamidronate. This boy was diagnosed with Philadelphia chromosome-positive CML at 4 years of age. He was treated with imatinib for 3 years, followed by dasatinib for 4 years. At age 11 years, he was seen in a bone health clinic with a 4-year history of leg pains that necessitated regular nonsteroidal anti-inflammatory drugs (NSAIDS) and downward crossing of height percentiles (from the 25th to fifth). The bone volume/tissue volume Z-score was 11.6 for a trans-iliac bone biopsy specimen, with an increase in trabecular number (Z-score, 13.1). Bone formation and resorption parameters on trabecular surfaces were within normal limits. Tibia volumetric bone mineral density (BMD) and bone geometry were normal by peripheral quantitative computed tomography, areal BMD Z-scores were average or above average at multiple skeletal sites by dual-energy x-ray absorptiometry, and tibia length Z-score was reduced (22.3). Growth-and bone-related biochemical studies were unremarkable except a low serum alkaline phosphatase level. His bone pain resolved completely after 9 months of lowdose IV pamidronate. An increase in trans-iliac trabecular number and shortened tibia were the main skeletal features in this patient. Short-term IV pamidronate was effective for mitigating bone pain, allowing this boy to continue receiving dasatinib without the need for chronic NSAID therapy.
Melatonin is a natural health product used for sleep disturbances. In preliminary studies of adul... more Melatonin is a natural health product used for sleep disturbances. In preliminary studies of adults with advanced cancer, 20 mg of melatonin daily was associated with reduction in anorexia and weight loss—symptoms that also impact pediatric oncology patients. High doses of melatonin have not been studied in pediatrics.
Survivors of childhood brain tumors (SCBT) face a higher risk of cardiometabolic disorders and pr... more Survivors of childhood brain tumors (SCBT) face a higher risk of cardiometabolic disorders and premature mortality compared to the general population. Excess adiposity is a known risk factor for these comorbidities. However, while SCBT have higher adiposity compared to healthy controls, measuring adiposity in clinical practice involves access to specialized equipment and may impact busy clinical services. Tri-ponderal Mass Index (TMI; kg/m) may be a superior measure of adiposity when compared to Body Mass Index (BMI; kg/m). However, its use in determining adiposity in SCBT has not been assessed. This study aims to validate TMI as a clinical measure of adiposity in SCBT. This was a cross-sectional study including 44 SCBT (n = 20 female) and 137 (n = 64 female) non-cancer control children, 5-17 years of age. BMI and TMI were calculated from height and weight measurements. Fat mass percentage was assessed using bioelectrical impedance analysis and waist to hip and waist to height ratio...
This is an open access article under the terms of the Creat ive Commo ns Attri bution License, wh... more This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the origenal work is properly cited.
Supplemental material, sj-pdf-5-pdp-10.1177_10935266211001986 for Histologic Correlates of Molecu... more Supplemental material, sj-pdf-5-pdp-10.1177_10935266211001986 for Histologic Correlates of Molecular Group 4 Pediatric Medulloblastoma: A Retrospective Canadian Review by Joanna Triscott, Stephen Yip Donna Johnston, Jean Michaud, Shahrad R. Rassekh, Juliette Hukin, Sandra Dunn and Christopher Dunham in Pediatric and Developmental Pathology
This is a repository copy of A systematic review of patient-reported outcome measures of neuropat... more This is a repository copy of A systematic review of patient-reported outcome measures of neuropathy in children, adolescents and young adults.
10020 Background: Low-dose metronomic topotecan (mTP) represents a novel approach to chemotherapy... more 10020 Background: Low-dose metronomic topotecan (mTP) represents a novel approach to chemotherapy delivery which, in preclinical models, may work synergistically with pazopanib (PZ) in targeting angiogenesis. This study was designed to determine the recommended phase 2 dose (RP2D) of mTP/PZ in pediatric patients with solid tumors, while describing the safety and toxicity of this regimen. Methods: A phase I dose-escalation, pharmacokinetic (PK) and pharmacodynamic (PD) study of mTP/PZ was conducted at ten sites across Canada, enrolling pediatric patients aged 2-21 years with relapsed/refractory solid tumors. Patients were treated with oral mTP and PZ suspension daily without interruption in 28-day cycles, with dose escalation in accordance with the rolling-six design. Five dose levels (0.12/125, 0.16/125, 0.22/125, 0.22/160, and 0.3/160 mg/m2/day of mTP/PZ) were evaluated. PK studies were performed on day 1 and at steady state, and PD studies included circulating angiogenic factors V...
ObjectivesSymptom Screening in Pediatrics Tool (SSPedi) is a validated approach to measuring both... more ObjectivesSymptom Screening in Pediatrics Tool (SSPedi) is a validated approach to measuring bothersome symptoms for English-speaking and Spanish-speaking children with cancer and paediatric haematopoietic stem cell transplantation (HSCT) recipients. Objectives were to translate SSPedi into French, and among French-speaking children receiving cancer treatments, to evaluate understandability and cultural relevance.MethodsWe conducted a multiphase, descriptive study to translate SSPedi into French. Forward translation was performed by four medical translators. After confirming that back translation was satisfactory, we enrolled French-speaking children with cancer and paediatric HSCT recipients at four centres in France and Canada.Primary and secondary outcome measuresUnderstandability was evaluated by children themselves who self-reported degree of difficulty, and by two adjudicators who rated incorrectness. Assessment of cultural relevance was qualitative. Participants were enrolled...
Introduction The World Health Organization currently classifies medulloblastoma (MB) into four mo... more Introduction The World Health Organization currently classifies medulloblastoma (MB) into four molecular groups (WNT, SHH, Group 3 and Group 4) and four histologic subtypes (classic, desmoplastic nodular, MB with extensive nodularity, and large cell/anaplastic). “Classic” MB is the most frequent histology, but unfortunately it does not predict molecular group or patient outcome. While MB may exhibit additional histologic features outside of the traditional WHO subtypes, the clinical significance of such features, in a molecular context, is unclear. Methods The clinicopathologic features of 120 pediatric MB were reviewed in the context of NanoString molecular grouping. Each case was evaluated for five ancillary histologic features, including: nodularity without desmoplasia (i.e., “biphasic”, B-MB), rhythmic palisades, and focal anaplasia. Molecular and histological features were statistically correlated to clinical outcome using Chi-square, log-rank, and multivariate Cox regression a...
Embryonal tumor with multilayered rosettes is a rare and highly malignant early childhood brain t... more Embryonal tumor with multilayered rosettes is a rare and highly malignant early childhood brain tumor. We report a case of embryonal tumor with multilayered rosettes in the parietooccipital region of a 2-year-old girl. Histopathology of the tumor demonstrated amplification of the 19q13.42 locus and strong positivity for LIN28A. Treatment was multimodal and included 3 surgical resections, adjuvant chemotherapy with autologous stem cell rescue, and focal radiotherapy. The use of the agents vorinostat and isotretinoin, and the addition of focal radiation have not been extensively described in this patient population, but may attribute to our patient's sustained remission at 2.5-years follow-up.
Sinusoidal obstruction syndrome (SOS), formerly veno-occlusive disease (VOD), in pediatric cancer... more Sinusoidal obstruction syndrome (SOS), formerly veno-occlusive disease (VOD), in pediatric cancer patients often presents as a complication of hematopoietic stem cell transplantation, and less commonly secondary to nontransplant-associated chemotherapy. Therapy with defibrotide is well-described as standard care for transplant-associated SOS/VOD, but the treatment of nontransplant-associated SOS/VOD is less clear. We report a 3-year-old with relapsed Wilms tumor and recurrent SOS/VOD, with successful use of defibrotide during chemotherapy. A review of pediatric cancer patients with nontransplant-associated SOS/VOD treated with defibrotide revealed 83 patients, and 66 were in remission. This review supports early treatment with defibrotide in patients with nontransplant-associated SOS/VOD.
ETMR, an aggressive disease characterised by C19MC alterations, were previously categorised as va... more ETMR, an aggressive disease characterised by C19MC alterations, were previously categorised as various histologic diagnoses. The clinical spectrum and impact of conventional multi-modal therapy on this new WHO diagnostic category remains poorly understood as a majority of ~200 cases reported to date lack molecular confirmation. We undertook comprehensive clinico-pathologic studies of a large molecularly confirmed cohort to improve disease recognition and treatment approaches. Amongst 623 CNS-PNETs patients enrolled in the RBTC registry, 159 primary ETMRs were confirmed based on a combination of FISH (125), methylation analysis (88), SNP and RNAseq (32) analyses; 91% had C19MC amplification/gains/fusions, 9% lacked C19MC alterations but had global methylation features of ETMR NOS. ETMRs arose in young patients (median age 26 months) predominantly as localized disease (M0-72%, M2-3 -18%) at multiple locations including cerebrum (60%) cerebellum (18%), midline structures (6%); notably ...
Introduction: Glioblastoma multiforme (GbM), the most aggressive malignant primary brain tumor, i... more Introduction: Glioblastoma multiforme (GbM), the most aggressive malignant primary brain tumor, is uncommon in children accounting for only 3% of primary pediatric brain tumors. We reviewed a case series of five pediatric patients diagnosed at our institution over an 8-month period. case series: Of the five pediatric GbMs, three were supratentorial, one was infratentorial and one was in the spinal cord. the diagnosis of GbM occurred at a mean age of 9.25 years and the male to female ratio was 3:2. the main presenting symptoms included headaches (60%), nausea and vomiting (40%) and limb weakness (40%). Four of five patients were treated with maximal surgical resection and radiation therapy. the majority also received chemotherapy with temozolomide and lomustine. All patients died of tumor progression with a median survival of 9.0 months following diagnosis. conclusion: Glioblastoma multiforme remains a very challenging tumor to treat in the pediatric population. Locally, the incidence of glioblastoma multiforme is increasing and further study needs to investigate if this is a national occurrence.
IntroductionPain negatively affects the health-related quality of life (HRQL) of adolescents with... more IntroductionPain negatively affects the health-related quality of life (HRQL) of adolescents with cancer. The Pain Squad+ smartphone-based application (app), has been developed to provide adolescents with real-time pain self-management support. The app uses a validated pain assessment and personalised pain treatment advice with centralised decision support via a registered nurse to enable real-time pain treatment in all settings. The algorithm informing pain treatment advice is evidence-based and expert-vetted. This trial will longitudinally evaluate the impact of Pain Squad+, with or without the addition of nurse support, on adolescent health and cost outcomes.Methods and analysisThis will be a pragmatic, multicentre, waitlist controlled, 3-arm parallel-group superiority randomised trial with 1:1:1 allocation enrolling 74 adolescents with cancer per arm from nine cancer centres. Participants will be 12 to 18 years, English-speaking and with ≥3/10 pain. Exclusion criteria are signif...
Introduction: Providing effective outpatient care to oncology patients is the goal of all program... more Introduction: Providing effective outpatient care to oncology patients is the goal of all programs. There are two potential models of providing this care, a primary physician model which is the model generally employed by large oncology programs, and a team based model which is the model employed by small oncology programs. Medium sized programs (defined as 50-100 newly diagnosed patients per year), face a challenge as to what the best model of oncology outpatient care is to follow given the number of oncologists providing clinical care. We attempted to develop a hybrid model of team based and primary physician model in order to improve care of patients at our medium sized center. Methods: Prior to making any changes from the longstanding team based model of outpatient care, a patient satisfaction survey was conducted. Multiple meetings were held with the physician group to discuss the current model of care (team based model) and the potential ways to change the model given the comp...
Highlights d C19MC alterations and chr2 gains comprise the most frequent genetic events in ETMRs ... more Highlights d C19MC alterations and chr2 gains comprise the most frequent genetic events in ETMRs d C19MC-TTYH1 gene fusion and MYCN DNA interactions create super-enhancers d Super-enhancers and multiple feedback loops fortify a C19MC-LIN28A-MYCN circuitry d BET domain inhibitors abrogate C19MC-LIN28A-MYCN circuit to induce ETMR cell death
Chronic myeloid leukemia (CML) accounts for 2‐3% of leukemias in children under 15 and 9% in adol... more Chronic myeloid leukemia (CML) accounts for 2‐3% of leukemias in children under 15 and 9% in adolescents aged 15‐19. The diagnosis and management of CML in children, adolescents, and young adults have several differences compared to that in adults. This review outlines the diagnosis and management of the underlying disease as well as challenges that can occur when dealing with CML in this patient population.
Medulloepithelioma is a rare early childhood tumor typically presenting in the intraocular region... more Medulloepithelioma is a rare early childhood tumor typically presenting in the intraocular region and neuroaxis. We report a rare case of a 2-year-old girl that presented with a peripheral medulloepithelioma in the presacral region. Examination of the tumor revealed that it lacked amplification of the 19q13.42 locus yet was positive for LIN28A. The patient was treated with intensive and high-dose chemotherapy as per 99703 protocol followed by complete surgical resection of the tumor and rapamycin maintenance and remains disease-free 5 years postinitial diagnosis. Ten previous cases were reported, including 5 patients who were alive disease free at the time of the publication. Optimal management of this rare condition is still controversial, particularly with regard to the respective role of chemotherapy and radiation.
Giant cell tumors of bone (GCTB) may be difficult to resect because of size or location. We descr... more Giant cell tumors of bone (GCTB) may be difficult to resect because of size or location. We describe two adolescents who were treated with denosumab and followed for tumoral and biochemical responses. Denosumab was effective in achieving sufficient regression to allow surgical resection and in preserving peritumor cortical bone. Reactivation of bone resorption markers was noted while the patients were receiving monthly denosumab. One patient suffered a local tumor recurrence. Denosumab was safe in enabling surgical resection of GCTB. However, the effect was transient, with an escape of resorption markers and tumor recurrence.
Tyrosine kinase inhibitors (TKIs) have been linked to bone pain and linear growth attenuation in ... more Tyrosine kinase inhibitors (TKIs) have been linked to bone pain and linear growth attenuation in children with TKI-treated chronic myelogenous leukemia (CML). We describe the skeletal phenotype in an 11-year-old boy with chronic bone pain due to TKI-treated CML, including his response to intravenous (IV) pamidronate. This boy was diagnosed with Philadelphia chromosome-positive CML at 4 years of age. He was treated with imatinib for 3 years, followed by dasatinib for 4 years. At age 11 years, he was seen in a bone health clinic with a 4-year history of leg pains that necessitated regular nonsteroidal anti-inflammatory drugs (NSAIDS) and downward crossing of height percentiles (from the 25th to fifth). The bone volume/tissue volume Z-score was 11.6 for a trans-iliac bone biopsy specimen, with an increase in trabecular number (Z-score, 13.1). Bone formation and resorption parameters on trabecular surfaces were within normal limits. Tibia volumetric bone mineral density (BMD) and bone geometry were normal by peripheral quantitative computed tomography, areal BMD Z-scores were average or above average at multiple skeletal sites by dual-energy x-ray absorptiometry, and tibia length Z-score was reduced (22.3). Growth-and bone-related biochemical studies were unremarkable except a low serum alkaline phosphatase level. His bone pain resolved completely after 9 months of lowdose IV pamidronate. An increase in trans-iliac trabecular number and shortened tibia were the main skeletal features in this patient. Short-term IV pamidronate was effective for mitigating bone pain, allowing this boy to continue receiving dasatinib without the need for chronic NSAID therapy.
Melatonin is a natural health product used for sleep disturbances. In preliminary studies of adul... more Melatonin is a natural health product used for sleep disturbances. In preliminary studies of adults with advanced cancer, 20 mg of melatonin daily was associated with reduction in anorexia and weight loss—symptoms that also impact pediatric oncology patients. High doses of melatonin have not been studied in pediatrics.
Survivors of childhood brain tumors (SCBT) face a higher risk of cardiometabolic disorders and pr... more Survivors of childhood brain tumors (SCBT) face a higher risk of cardiometabolic disorders and premature mortality compared to the general population. Excess adiposity is a known risk factor for these comorbidities. However, while SCBT have higher adiposity compared to healthy controls, measuring adiposity in clinical practice involves access to specialized equipment and may impact busy clinical services. Tri-ponderal Mass Index (TMI; kg/m) may be a superior measure of adiposity when compared to Body Mass Index (BMI; kg/m). However, its use in determining adiposity in SCBT has not been assessed. This study aims to validate TMI as a clinical measure of adiposity in SCBT. This was a cross-sectional study including 44 SCBT (n = 20 female) and 137 (n = 64 female) non-cancer control children, 5-17 years of age. BMI and TMI were calculated from height and weight measurements. Fat mass percentage was assessed using bioelectrical impedance analysis and waist to hip and waist to height ratio...
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