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A PROSPECTIVE STUDY ON AVAILABILITY OF ESSENTIAL MEDICINES FOR TREATMENT OF CHILDHOOD CANCER IN SRI LANKA
Abstract
Background and Aims
World Health Organization(WHO) Model List of Essential Medicines for children(EMLc 2019) contains 39 antineoplastic and supportive medicines deemed essential for successful treatment of children with cancer. There is variable availability of these medicines in many countries, but most reports are retrospective or short-term. This study describes the availability of these medicines in Sri Lanka’s only treatment centre for childhood cancer, the National Cancer Institute, Sri Lanka,over one year.
Methods
We prospectively tracked availability of essential medicines at NCISL in a custom-made database from April 2019 to March 2020. Consumption volumes and unit priceswere extracted from the Ministry of Health Medical Supplies Management Information System. Availability was mapped against regimens in Sri Lanka, and SIOP Pediatric Oncology in Developing Countries(PODC)
Results
31/39 drugs are in the Sri Lankan EML and 36/39 (48 formulations) are registered for use. Thioguanine, Arsenic and Realgar-Indigo Naturalis were unregistered. Overthe study period, 17 medicines were available 100% of the time. Least available was procarbazine (58%). No day had100% availability of medicines; best availability was in August and worst in January. Applying regimen-based analyses, for acute lymphoblastic leukemia, 12 stockout episodes affected 7 medicines (median 37.5 consecutive days, range 4-104), while stockout mitigation strategies (low stock periods not resulting in stockout) were effective in 11 instances;only 3 medicines did not have alternate formulations/substitutions during stockouts (vincristine, cytarabine, and 6MP). Of the WHO Global Initiative index cancers Hodgkin lymphoma was most affected, retinoblastoma least. Annual consumption volumes (p=0.13), unit and annual costs (p=0.5 and 0.09) were not significantly associated with medicine unavailability
Conclusions
Non-availability of essential medicines is a significant problem to be addressed for children with cancer in Sri Lanka. This study demonstrated the feasibility of prospective essential medicines tracking at the point-of-care, and how data visibility can inform stock and inventory management, and help identify mitigation strategies for stockouts.
A GLOBAL APPROACH FOR THE CLASSIFICATION AND SEVERITY GRADING OF ESSENTIAL ADVERSE EVENTS (EAE) AMONG CHILDREN WITH CANCER
- Sharmeen Hussain, United States of America
- Alisha Gray, United States of America
- Lane Faughnan, United States of America
- Abdelhafeez H. Abdelhafeez, United States of America
- Sahaja Acharya, United States of America
- Asya Agulnik, United States of America
- Justin N. Baker, United States of America
- Rachel C. Brennan, United States of America
- Paola Friedrich, United States of America
- Sima Jeha, United States of America
- Catherine Lam, United States of America
- John T. Lucas Jr., United States of America
- Daniel Moreira, United States of America
- Monika Metzger, United States of America
- Sheena Mukkada, United States of America
- Ibrahim Qaddoumi, United States of America
- Alia Zaidi, United States of America
- Carlos Rodriguez-Galindo, United States of America
- Nickhill Bhakta, United States of America
Abstract
Background and Aims
Monitoring treatment associated morbidity is key to measuring the quality of childhood cancer care delivery. The National Cancer Institute Common Terminology Criteria for Adverse Events v5 (CTCAE) is the gold standard for adverse event reporting. However, with over 822 terms, implementation of the CTCAE is not feasible in most resource-limited settings. To address this gap, we developed the Essential Adverse Events (EAE) grading rubric.
Methods
A three-round modified Delphi was conducted to define EAEs. A multidisciplinary panel of 14 physicians with pediatric oncology, infectious diseases, radiation oncology, critical care and surgery expertise from the St. Jude Global team was assembled. The panel was enriched with additional subspecialists post-hoc. In the first round, panelists were asked to identify the 50 CTCAE most relevant to resource-limited settings. A subset of selected CTCAE were further revised by panelists to 25 events in a second round. Overlapping terms were provisionally consolidated, definitions edited, and individual grade criteria adapted by content experts. The third round, an in-person panel discussion to finalize definitions and grades for each condition, was completed to attain a final consensus list of EAEs.
Results
During round one, 664/822 (81%) CTCAE were selected by one or more respondents and 88/822 (11%) received >2 votes. In round two, 72/88 (82%) CTCAE received at least one vote and 54/88 (61%) received >2. All 54 terms were reviewed and with input from term-specific content specialists, 26 EAEs were identified. Following the panel discussion in round three, consensus was obtained for 25 EAE terms, definitions, and grades.
Conclusions
We developed a list of 25 EAEs designed for use in resource-limited settings. These terms can be used for clinical trials or routine monitoring of treatment guidelines. A second phase modified-Delphi employing a globally representative panel with content experts and patient advocates is under development as a validation step.
PRE-TREATMENT FASTING AS A MEANS TO PREVENT CHEMOTHERAPY-INDUCED SIDE EFFECTS
Abstract
Background and Aims
Over the last decades improved treatment schedules have led to increased survival for paediatric oncology patients. Therefore, acute side effects and long-term consequences evoked by therapy are now amongst the most pressing problems. These consequences include many features of ageing-like disorders. Radio- and chemotherapy cause DNA damage which is known to accelerate ageing and can lead to the aforementioned pathologies. We previously showed that dietary restriction (30% reduced food intake) and short-term fasting trigger a ‘survival response’, delaying ageing, diminishing ageing-related pathologies and boosting defence mechanisms. Here we investigated in a preclinical setting whether fasting prior to DNA-damaging treatments prevents therapy-induced side effects.
Methods
Young wildtype mice were preconditioned with ad libitum (AL) diet or a two-day fasting period followed by radio- or chemotherapy, e.g. cisplatin (10 or 20 mg/kg), doxorubicin (12 mg/kg) or vincristine (0.5 mg/kg). Body weight, food intake and activity were monitored until moment of sacrifice (3 days, 8 days or 6 months after treatment). Subsequently, blood and several organs were collected for further analysis.
Results
Mice exposed to radio- or chemotherapy showed decreased appetite after treatment. Adverse effects on body weight, activity, food intake and water intake were less severe in fasted mice compared to AL fed controls. High-dose cisplatin treatment appeared to be lethal for AL fed animals, and death was prevented in 40% of fasted mice (p = 0.0174). Additionally, several phenotypical signs of nephrotoxicity were reduced by fasting.
Conclusions
The effects of chemotherapy on body weight and subsequent food intake in the presented preclinical model resemble clinical observations. Fasting was shown to (partially) prevent those effects, as well as acute toxicity provoked by high-dose cisplatin treatment. Translation of current findings into treatment regimens for paediatric oncology patients may prevent or reduce multiple short- and long-term health conditions and improve overall quality of life.
SMELL AND TASTE FUNCTION IN CHILDREN WITH CANCER: A FEASIBILITY STUDY
Abstract
Background and Aims
Chemotherapy can affect smell and taste function, however, this has never been investigated in children with cancer. The objective of this study was to determine whether psychophysical smell and taste tests are suitable for children with cancer. Taste and smell function, fungiform papillae density, and eating behavior were measured before and after a cycle of chemotherapy, and compared with healthy controls.
Methods
Thirty-one children with cancer and 24 healthy controls participated. Smell function was measured using Sniffin’ Sticks, including a threshold, discrimination, and identification test. Taste Strips were used to determine recognition thresholds for sweet, sour, salty, and bitter taste. Papillae density was investigated by counting the fungiform papillae of the anterior tongue. Eating behavior was assessed using the Behavioral Pediatrics Feeding Assessment Scale (BPFAS).
Results
Smell and taste function could be investigated in more than 90% of the patients, while fungiform papillae density could be determined for 61% of the patients. Compared to controls, patients had a lower smell and sour taste threshold (p < 0.05). Patients showed an increased score for sweet (p < 0.001), bitter (p = 0.028), and total taste function (p = 0.004) after a cycle of chemotherapy.
Conclusions
This study demonstrates that the assessment of smell and taste function and fungiform papillae density is feasible in children with cancer. In addition, results of the current study suggest a heightened smell and taste sensitivity in children with cancer.
CEREBROSPINAL FLUID METABOLOMIC PROFILES ASSOCIATED WITH FATIGUE DURING TREATMENT FOR PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)
- Austin Brown, United States of America
- Pagna Sok, United States of America
- Olga A. Taylor, United States of America
- Brooke Bernhardt, United States of America
- Kimberly P. Raghubar, United States of America
- Lisa Kahalley, United States of America
- Philip J. Lupo, United States of America
- Marilyn Hockenberry, United States of America
- Michael E. Scheurer,
Abstract
Background and Aims
Cancer-related fatigue (CRF) is one of the most prevalent, distressing, and persistent symptoms reported during ALL therapy; however, information on the pathophysiology of CRF is limited. Therefore, we conducted global metabolomic profiling of cerebrospinal fluid (CSF) samples to identify biomarkers for CRF during pediatric ALL treatment.
Methods
We enrolled pediatric ALL patients (age 3-18 years) at Texas Children’s Hospital (2012-2017). Fatigue was assessed at delayed intensification (DI) therapy using the validated Childhood Fatigue Scale (ages 7-12 years), Adolescent Fatigue Scale (13-18 years), or proxy-reported Parent Fatigue Scale (3-6 years). CSF was collected at DI on 171 participants, comprising discovery (n=86) and replication (n=85) cohorts. Diagnostic CSF was available on 48 individuals in the replication cohort. We performed CSF metabolomic profiling using gas chromatography-mass spectrometry (MS) and liquid chromatography-MS/MS. Kendall’s rank correlation was used to evaluate associations between metabolite abundance and CRF, applying a false discovery rate (FDR) correction for multiple comparisons.
Results
Participants were 56% male, 59% Hispanic, and 64% high/very high-risk with a mean age at diagnosis of 8.5 years. Metabolomics detected 313 metabolites in discovery and 409 metabolites in replication CSF, including 274 common to both cohorts. Eight metabolites were significantly associated with fatigue in the discovery cohort (p<0.05), of which three demonstrated consistent effects in the replication cohort (p<0.05). Of the replicated metabolites, gamma-glutamylglutamine (p = 6.2E-6) and asparagine (p = 3.5E-4) achieved FDR-corrected statistical significance in the combined cohort, associations which remained after accounting for clinical factors. Notably, the abundance of gamma-glutamylglutamine in diagnostic CSF samples was also inversely associated with fatigue during DI (p=0.0062).
Conclusions
We identified and replicated significant associations between fatigue and CSF metabolites potentially involved in neurotransmitter transportation and glutathione recycling in the central nervous system, suggesting glutamatergic pathways or oxidative stress may contribute to CRF in pediatric ALL patients.
ONCO-FERTILITY CARE FOR NEWLY DIAGNOSED GIRLS WITH CANCER IN A NATIONAL PEDIATRIC ONCOLOGY SETTING, THE FIRST EXPERIENCES FROM THE PRINCESS MÁXIMA CENTER, THE PEARL STUDY.
- M. E. Madeleine Van der Perk, Netherlands
- Anne-Lotte F. Van der Kooi, Netherlands
- Marianne D. Van de Wetering, Netherlands
- Irene M. IJgosse, Netherlands
- Eline Van Dulmen-den Broeder, Netherlands
- Simone L. Broer, Netherlands
- Margreet A. Veening, Netherlands
- Aart J. Klijn, Netherlands
- A. Birgitta Versluys, Netherlands
- Brigitte Arends, Netherlands
- Ralph J.A. Oude Ophuis, Netherlands
- Hanneke M. Van Santen, Netherlands
- Alida F.W. Van der Steeg, Netherlands
- Marry M. Van den Heuvel-Eibrink, Netherlands
- Annelies M.E. Bos, Netherlands
Abstract
Background and Aims
Infertility is one of the most life-altering potential consequences of childhood cancer treatment. Nonetheless, onco-fertility care at diagnosis does not always have the highest priority, leaving patients often uninformed of their potential risk of gonadal damage. In our hospital we introduced a standard onco-fertility care-plan, including 1)timely identification of new patients, 2)early triage on gonadal damage risk, 3)personalized information, 4)subsequent counseling of girls at risk and 5)offering ovarian tissue cryopreservation(OTC) to patients at high risk of gonadal damage. To optimize rapid triage, we included standardized estimated gonadal damage risk(low, intermediate, high) of current European treatment protocols based on amended Edinburgh criteria including cyclophosphamide equivalent dose(CED). Here we aimed to evaluate our standard of care.
Methods
In this PEARL (PrEserving ovARian function through cryopreservation and informing girLs with cancer about infertility due to gonadotoxic treatment) study, we retrospectively evaluated the first full year of applying this female onco-fertility care plan in our national center(2019), focusing on triage, timing and content of the informative process, subsequent counseling and fertility preservation in newly diagnosed girls with pediatric cancer.
Results
Out of 262 newly diagnosed girls with cancer, 219 had been timely identified, before start of cancer treatment. Triage by the onco-fertility team resulted in 180 low, 32 intermediate and 48 high risk estimated gonadal damage patients(2 early deaths). Ultimately, 35 girls were counseled by a fertility expert, of which 15 underwent fertility preservation(14 OTC) without complications.
Conclusions
Our structured onco-fertility care-plan identified most girls with cancer with a high risk of gonadal damage to be counseled for fertility preservation. A risk stratification per treatment protocol and arm using the combination of Edinburgh criteria and CED, aids in the rapid triage process, enhances information provision to families and selection of girls for fertility counseling and preservation before start of cancer treatment, based on individual scheduled treatment protocol.
Live Q&A
- Sharmeen Hussain, United States of America
- Winnie M. Van den Boogaard, Netherlands
- Mirjam Van den Brink, Netherlands
- Austin Brown, United States of America
- M. E. Madeleine Van der Perk, Netherlands
- Trijn Israels, Netherlands
- Sanjeeva Gunasekera, Sri Lanka
- Kjeld Schmiegelow, Denmark
- Adam J. Esbenshade,
- Sharmeen Hussain, United States of America
- Winnie M. Van den Boogaard, Netherlands
- Mirjam Van den Brink, Netherlands
- Austin Brown, United States of America
- M. E. Madeleine Van der Perk, Netherlands
- Trijn Israels, Netherlands
- Sanjeeva Gunasekera, Sri Lanka
- Kjeld Schmiegelow, Denmark
- Adam J. Esbenshade,