Should Adolescents With Acute Lymphoblastic Leukemia Be Treated as Old Children or Young Adults? Comparison of the French FRALLE-93 and LALA-94 Trials

Boissel, Nicolas; Auclerc, Marie-Françoise; Lhéritier, Véronique; Pérel, Yves; Thomas, Xavier; Leblanc, Thierry; Rousselot, Philippe; Cayuela, Jean‐Michel; Gabert, Jean; Fégueux, Nathalie; Piguet, Christophe; Huguet-Rigal, Françoise; Berthou, Christian; Boiron, Jean‐Michel; Pautas, Cécile; Gautier, Michel; Fière, D; Leverger, Guy; Dombret, Hervé; Baruchel, André

doi:10.1200/jco.2003.02.053

Cited by 534 publications

(399 citation statements)

References 23 publications

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“…6 It has been widely speculated that clinicians believe that adults tolerate treatment less well than children, [9][10][11] and chemotherapy dose intensity in adult acute lymphoblastic leukaemia (ALL) protocols was lower than in paediatric protocols. 4 Other contributing factors may include delayed clinical presentation and compliance issues. 12,13 Both host and tumor biology of AYA cancers are emerging areas of research, which are likely relevant to survival.…”

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confidence: 99%

“…1 For many cancers, survival for AYAs is significantly worse than for children. 4,5 The reasons behind the meagre improvements in survival for AYA cancer are poorly understood. Low participation rates for AYAs in clinical trials, particularly in comparison to paediatric patients, correlates with outcomes.…”

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confidence: 99%

“…Low participation rates for AYAs in clinical trials, particularly in comparison to paediatric patients, correlates with outcomes. [6][7][8] Survival has been linked to treatment on paediatric protocols, 4 or to treatment at specialized paediatric centers. 6 It has been widely speculated that clinicians believe that adults tolerate treatment less well than children, [9][10][11] and chemotherapy dose intensity in adult acute lymphoblastic leukaemia (ALL) protocols was lower than in paediatric protocols.…”

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confidence: 99%

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Gender‐specific activity of chemotherapy correlates with outcomes in chemosensitive cancers of young adulthood

Khamly

Thursfield

Fay

et al. 2009

Intl Journal of Cancer

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Good evidence indicates that adolescents and young adults (AYAs) with cancer do badly compared with children with similar cancers. The reasons are poorly understood. Australian registry data on 14,824 cancers of adolescence and young adulthood seen between 1982 and 2002 were reviewed. A detailed substudy of clinical characteristics was analyzed from 179 AYAs with Hodgkin lymphoma (HL), Ewing sarcoma (ES) or osteosarcomas (OS) treated at a single institution. Despite significant improvements in survival for both groups over the period in question, for acute lymphoblastic leukaemia, rhabdomyosarcoma, ES, OS and HL, survival for AYAs was worse than for children. For ES, OS and HL, the survival gap occurred almost entirely in males (Hazard ratios compared with female AYAs of 1.8 [p < 0.01], 1.4 [p = 0.03] and 1.5 [p < 0.01] respectively). Survival outcomes from ES, OS and HL for female AYAs were not significantly different from children of either sex. For brain tumors and thyroid cancers, which are primarily treated surgically, there were no gender‐related differences in outcomes. Although no differences in tumor stage or compliance were identified, male AYAs experienced less toxicity and lower response rates to chemotherapy (p = 0.008). Young males account almost entirely for excess mortality from chemosensitive cancers of adolescence and young adulthood compared to children, which may be due to relative underdosing with current chemotherapy dosing algorithms. © 2009 UICC

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Gender‐specific activity of chemotherapy correlates with outcomes in chemosensitive cancers of young adulthood

Khamly

Thursfield

Fay

et al. 2009

Intl Journal of Cancer

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“…7 Hematólogo Panda Hospital sótero del río. 8 Hematólogo Panda Hospital Barros luco trudeau. 9 Hematólogo Panda Hospital de talca.…”

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“…Este grupo de pacientes es clasificado de alto riesgo en grupos pediátricos, recibiendo esquemas de quimioterapia intensificados, con un mayor cumplimiento y adherencia. Más recientemente el uso de esquemas intensificados utilizados en pacientes adultos entre 15 y 45 años muestran una mejoría en la sobrevida global (SG), 62% a 5 años [6][7][8][9][10][11] . El Programa Nacional de Cáncer del Adulto (PANDA) ha incorporado diferentes protocolos para el tratamiento de la LLA, desde su inicio en 1988.…”

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Leucemia linfoblástica aguda estirpe B Philadelphia negativa en adolescentes y adultos jóvenes: Resultados del Protocolo Terapéutico LLA 15-30, Programa Nacional de Cáncer del Adulto (PANDA), Ministerio de Salud, Chile

Puga¹,

Guerra²,

Molina

et al. 2014

Rev. méd. Chile

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Association Between Younger Age and Targetable Genomic Alterations and Prognosis in Non–Small-Cell Lung Cancer

et al. 2016

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Importance NSCLC in the young is a rare entity and the genomics and clinical characteristics of this disease are poorly understood. In contrast, young age at diagnosis has been demonstrated to define unique disease biology in other cancers. Here we report on the association of young age with targetable genomic alterations and prognosis in a large cohort of NSCLC patients. Objective To determine the relationship between young age at diagnosis and both the presence of a potentially targetable genomic alteration as well as prognosis and natural history. Design All patients with NSCLC genotyped at the Dana-Farber Cancer Institute between 2002–2014 were identified. Tumor genotype, patient characteristics and clinical outcomes were collected. Multivariate logistic regression was used to analyze the relationship between age and mutation status. Multivariate Cox proportional hazard models were fitted for survival analysis. Setting A National Cancer Institute (NCI) designated comprehensive cancer center. Participants All patients with NSCLC seen at the Dana-Farber Cancer Institute between 2002–2014 who underwent tumor genotyping. Main Outcome Measure The frequency of targetable genomic alterations by defined age categories as well as the association of these age groups with survival. Results 2237 patients with NSCLC were studied. EGFR (p=0.02) and ALK (P<0.01) were associated with younger age, and a similar trend existed for HER2 (p=0.15) and ROS1 (p=0.1) but not BRAF V600E (p=0.43). Amongst patients tested for all 5 targetable genomic alterations, younger age was associated with an increased frequency of a targetable genotype (p<0.01). Those diagnosed at age 50 or younger have a 59% increased likelihood of harboring a targetable genotype. While presence of a potentially targetable genomic alteration treated with a targeted agent was associated with improved survival, the youngest and oldest age groupings had similarly poor outcomes even when a targetable genotype was present. Conclusion & Relevance Younger age is associated with an increased likelihood of harboring a targetable genotype and is an underappreciated clinical biomarker in NSCLC. The survival of young NSCLC patients is unexpectedly poor compared to other age groups, suggesting more aggressive disease biology. These findings underscore the importance of comprehensive genotyping including NGS in younger patients with lung cancer.

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Should Adolescents With Acute Lymphoblastic Leukemia Be Treated as Old Children or Young Adults? Comparison of the French FRALLE-93 and LALA-94 Trials

Abstract: This study's findings indicate that adolescents should be included in intensive pediatric protocols and that new trials should be designed, inspired by pediatric protocols, for the treatment of young adults with ALL.

Cited by 534 publications

References 23 publications

Gender‐specific activity of chemotherapy correlates with outcomes in chemosensitive cancers of young adulthood

Gender‐specific activity of chemotherapy correlates with outcomes in chemosensitive cancers of young adulthood

Leucemia linfoblástica aguda estirpe B Philadelphia negativa en adolescentes y adultos jóvenes: Resultados del Protocolo Terapéutico LLA 15-30, Programa Nacional de Cáncer del Adulto (PANDA), Ministerio de Salud, Chile

Association Between Younger Age and Targetable Genomic Alterations and Prognosis in Non–Small-Cell Lung Cancer

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