9 research outputs found
Global Retinoblastoma Presentation and Analysis by National Income Level.
Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs
The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries
DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt
Perbedaan Kebutuhan Transfusi Darah Selama Fase Induksi pada Leukemia Limfoblastik Akut
Latar belakang. Terapi transfusi adalah salah satu terapi kunci dalam pengelolaan kanker dan penyakit
darah pada anak. Hanya sedikit laporan tentang kuantitatif aspek transfusi sel darah merah dan trombosit
pada penyakit leukemia limfoblastik akut (LLA). Fase induksi sangat berbahaya pada terapi LLA, karena
sumsum tulang mengalami supresi yang diakibatkan oleh kemoterapi intensif. Fase induksi meliputi
pemberian obat-obat methotrexate, vincristine, L-asp, daunorubicin, dan kortikosteroid selama 6 minggu.
Protokol Indonesia 2006 terdiri dari 3 fase (induksi, konsolidasi, pemeliharaan) pada kelompok risiko standar
(standard risk/SR) dan ditambah fase re-induksi untuk kelompok risiko tinggi (high risk/HR).Kuantitas
transfusi dikaitkan dengan masalah efek samping dan biaya.
Tujuan. Menilai perbedaan kebutuhan transfusi darah pasien LLA risiko standar dan tinggi yang diterapi dengan Protokol Indonesia 2006.
Metode. Studi retrospektif dilakukan selama bulan Juli 2006 sampai Desember 2010 tentang kebutuhan transfusi selama fase induksi pada pasien baru LLA yang mendapat terapi dengan Protokol Indonesia 2006 di RS Dr Kariadi Semarang. Pasien diklasifikasikan menjadi kelompok risiko standar dan tinggi menurut kriteria NCI. Dibandingkan jumlah transfusi packed red cell(PRC) dan thrombocyte concentrate(TC) per luas permukaan tubuh (basal surface area/BSA).Analisis statistik menggunakan chi square(X2).
Hasil. Subyek 160 pasien, namun hanya 119 (74,3%) pasien yang dapat dievaluasi. Perbandingan kelompok
SR:HR 59,7:40,3. Rerata BSA pada kelumpok SR dan HR berturut turut 0,66 (SD±0,19)m2dan 0,77/m2 (SD±0,22), p<0,001. Selama fase induksi didapatkan rerata pemakaian PRC per pasien pada kelompok SR dan HR berturut turut 530 ml dan 420ml (p=0,79), pada TC 13 dan 11 unit (p= 0,19).Rasio penggunaan komponen PRC/BSA berturut turut untuk SR: HR 843:543 ml/m2untuk komponen TC 21:15 unit/m2.
Kesimpulan. Tidak terdapat perbedaan bermakna antara kebutuhan kelompok risiko standar dan tinggi terhadap
kebutuhan transfusi komponen darah PRC dan TC selama fase induksi
Event Free Survival Enam Bulan Kejadian Tumor Cachexia Syndrome pada Anak dengan Keganasan
Latar belakang. Jumlah kasus kanker pada anak dengan komplikasi tumor cachexia syndrome (TCS) terus
meningkat. Penyebab TCS bersifat multifaktorial, yaitu asupan makanan yang kurang, malabsorbsi, dan
sitokin oleh tumor. Pengelolaan pasien anak dengan keganasan di rumah sakit tidak hanya dari terapi anti
kanker tetapi juga nutrisi. Nilai event free survival (EFS) terhadap kejadian TCS merupakan salah satu
indikator keberhasilan pengelolaan kanker di rumah sakit.
Tujuan. Menentukan EFS 6 bulan terhadap kejadian TCS pada pasien anak dengan keganasan.
Metode. Desain kohort retrospektif berdasarkan catatan medik pasien anak dengan keganasan yang dirawat
di RSUP Dr. Kariadi Semarang pada bulan Januari 2007 - Desember 2012. Kriteria inklusi adalah pasien
usia 0-14 tahun, dengan diagnosis keganasan baik tumor padat maupun hematologi, dan tidak mengalami
kakeksia pada saat diagnosis ditegakkan. Dilakukan pengamatan secara klinis dan laboratoris tiap bulan
selama 6 bulan untuk menentukan terjadinya TCS. Analisis statistik menggunakan uji Kaplan Meier.
Hasil. Didapatkan 83 subjek dengan keganasan, rerata umur pada kelompok tumor padat 61,2 (SD
48,37) bulan, dan keganasan hematologi 79,9 (SD 48,37) bulan p=0,032. Empatbelas dari 40 (35%) anak
tumor padat dan 10 dari 43(23,3%) anak dengan keganasan hematologi mengalami TCS. Kejadian TCS
didapatkan mulai pengamatan bulan kedua. Rerata terjadi TCS pada tumor padat 4,4 bulan dan pada
keganasan hematologi 4,9 bulan. Event free survival 6 bulan kejadian TCS pada tumor padat 65% dan
keganasan hematologi 76,7%, p= 0,207.
Kesimpulan. Event free survival 6 bulan kejadian TCS pada pasien tumor padat lebih rendah daripada
keganasan hematologi, tetapi tidak berbeda secara statisti
Advancing access and equity : the vision of a new generation in cancer control
We must dramatically alter the current trajectory of cancer care to ensure that improvements are accessible by all in the global community. We must bridge the gap between what is achievable and what is accessible. We must act with urgency and precision, recognising the tremendous social and economic costs of inaction. The first priority should be to reframe cancer care. Second, we need to identify different measures of cancer outcomes. Third, we need to challenge extant priorities
A personal COVID-19 dendritic cell vaccine made at point-of-care: Feasibility, safety, and antigen-specific cellular immune responses
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a world-wide pandemic. Internationally, because of availability, accessibility, and distribution issues, there is a need for additional vaccines. This study aimed to: establish the feasibility of personal dendritic cell vaccines to the SARS-CoV-2 spike protein, establish the safety of a single subcutaneous vaccine injection, and determine the antigen-specific immune response following vaccination. In Phase 1, 31 subjects were assigned to one of nine formulations of autologous dendritic cells and lymphocytes (DCL) incubated with 0.10, 0.33, or 1.0 µg of recombinant SARS-CoV-2 spike protein, and admixed with saline or 250 or 500 µg of granulocyte-macrophage colony-stimulating factor (GM-CSF) prior to injection, then assessed for safety and humoral response. In Phase 2, 145 subjects were randomized to one of three formulations defined by incubation with the same three quantities of spike protein without GM-CSF, then assessed for safety and cellular response. Vaccines were successfully manufactured for every subject at point-of-care. Approximately 46.4% of subjects had a grade 1 adverse event (AE); 6.5% had a grade 2 AE. Among 169 evaluable subjects, there were no acute allergic, grade 3 or 4, or serious AE. In Phase 1, anti-receptor binding domain antibodies were increased in 70% of subjects on day-28. In Phase 2, in the 127 subjects who did not have high levels of gamma interferon-producing cells at baseline, 94.4% had increased by day 14 and 96.8% by day 28. Point-of-care personal vaccine manufacturing was feasible. Further development of such subject-specific vaccines is warranted
The Global Retinoblastoma Outcome Study: a prospective, cluster-based analysis of 4064 patients from 149 countries
Background Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. Methods We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1,2017, and Dec 31,2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. Findings The cohort included 4064 children from 149 countries. The median age at diagnosis was 23.2 months (IQR 11.0-36.5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0.8%) of 636 children from high-income countries, 55 (5.4%) of 1027 children from upper-middle-income countries, 342 (19. 7%) of 1738 children from lower-middle-income countries, and 196 (42.9%) of 457 children from low-income countries. Enudeation surgery was available for all children and intravenous chemotherapy was available for 4014 (98.8%) of 4064 children. The 3-year survival rate was 99.5% (95% CI 98.8-100.0) for children from high-income countries, 91.2% (89.5-93.0) for children from upper-middle-income countries, 80.3% (78.3-82.3) for children from lower-middle-income countries, and 57.3% (524-63-0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16.67; 95% CI 4.76-50.00), cT4 advanced tumour compared to cT1 (8.98; 4.44-18.18), and older age at diagnosis in children up to 3 years (1.38 per year; 1.23-1.56). For children aged 3-7 years, the mortality risk decreased slightly (p=0.0104 for the change in slope). Interpretation This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.Y
Global Retinoblastoma Presentation and Analysis by National Income Level
This cross-sectional analysis reports the retinoblastoma stage at
diagnosis across the world during a single year, investigates
associations between clinical variables and national income level, and
investigates risk factors for advanced disease at diagnosis.
Key PointsQuestionIs the income level of a country of residence
associated with the clinical stage of presentation of patients with
retinoblastoma? FindingsIn this cross-sectional analysis that included
4351 patients with newly diagnosed retinoblastoma, approximately half of
all new retinoblastoma cases worldwide in 2017, 49.1\% of patients from
low-income countries had extraocular tumor at time of diagnosis compared
with 1.5\% of patients from high-income countries. MeaningThe clinical
stage of presentation of retinoblastoma, which has a major influence on
survival, significantly differs among patients from low-income and
high-income countries, which may warrant intervention on national and
international levels.
ImportanceEarly diagnosis of retinoblastoma, the most common intraocular
cancer, can save both a child's life and vision. However, anecdotal
evidence suggests that many children across the world are diagnosed
late. To our knowledge, the clinical presentation of retinoblastoma has
never been assessed on a global scale. ObjectivesTo report the
retinoblastoma stage at diagnosis in patients across the world during a
single year, to investigate associations between clinical variables and
national income level, and to investigate risk factors for advanced
disease at diagnosis. Design, Setting, and ParticipantsA total of 278
retinoblastoma treatment centers were recruited from June 2017 through
December 2018 to participate in a cross-sectional analysis of
treatment-naive patients with retinoblastoma who were diagnosed in 2017.
Main Outcomes and MeasuresAge at presentation, proportion of familial
history of retinoblastoma, and tumor stage and metastasis. ResultsThe
cohort included 4351 new patients from 153 countries; the median age at
diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976
patients (45.4\%) were female. Most patients (n=3685 {[}84.7\%]) were
from low- and middle-income countries (LMICs). Globally, the most common
indication for referral was leukocoria (n=2638 {[}62.8\%]), followed by
strabismus (n=429 {[}10.2\%]) and proptosis (n=309 {[}7.4\%]). Patients
from high-income countries (HICs) were diagnosed at a median age of 14.1
months, with 656 of 666 (98.5\%) patients having intraocular
retinoblastoma and 2 (0.3\%) having metastasis. Patients from low-income
countries were diagnosed at a median age of 30.5 months, with 256 of 521
(49.1\%) having extraocular retinoblastoma and 94 of 498 (18.9\%) having
metastasis. Lower national income level was associated with older
presentation age, higher proportion of locally advanced disease and
distant metastasis, and smaller proportion of familial history of
retinoblastoma. Advanced disease at diagnosis was more common in LMICs
even after adjusting for age (odds ratio for low-income countries vs
upper-middle-income countries and HICs, 17.92 {[}95\% CI, 12.94-24.80],
and for lower-middle-income countries vs upper-middle-income countries
and HICs, 5.74 {[}95\% CI, 4.30-7.68]). Conclusions and RelevanceThis
study is estimated to have included more than half of all new
retinoblastoma cases worldwide in 2017. Children from LMICs, where the
main global retinoblastoma burden lies, presented at an older age with
more advanced disease and demonstrated a smaller proportion of familial
history of retinoblastoma, likely because many do not reach a
childbearing age. Given that retinoblastoma is curable, these data are
concerning and mandate intervention at national and international
levels. Further studies are needed to investigate factors, other than
age at presentation, that may be associated with advanced disease in
LMICs