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- Ambros, I. M., et al.
(författare)
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Age Dependency of the Prognostic Impact of Tumor Genomics in Localized Resectable MYCN-Nonamplified Neuroblastomas. Report From the SIOPEN Biology Group on the LNESG Trials and a COG Validation Group
- 2020
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 38:31
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSEFor localized, resectable neuroblastoma without MYCN amplification, surgery only is recommended even if incomplete. However, it is not known whether the genomic background of these tumors may influence outcome.PATIENTS AND METHODSDiagnostic samples were obtained from 317 tumors, International Neuroblastoma Staging System stages 1/2A/2B, from 3 cohorts: Localized Neuroblastoma European Study Group I/II and Children's Oncology Group. Genomic data were analyzed using multi- and pangenomic techniques and fluorescence in-situ hybridization in 2 age groups (cutoff age, 18 months) and were quality controlled by the International Society of Pediatric Oncology European Neuroblastoma (SIOPEN) Biology Group.RESULTSPatients with stage 1 tumors had an excellent outcome (5-year event-free survival [EFS] standard deviation [SD], 95% +/- 2%; 5-year overall survival [OS], 99% +/- 1%). In contrast, patients with stage 2 tumors had a reduced EFS in both age groups (5-year EFS +/- SD, 84% +/- 3% in patients < 18 months of age and 75% 7% in patients >= 18 months of age). However, OS was significantly decreased only in the latter group (5-year OS +/- SD in < 18months and 18months, 96% +/- 2% and 81% +/- 7%, respectively; P = .001). In < 18months, relapses occurred independent of segmental chromosome aberrations (SCAs); only 1p loss decreased EFS (5-year EFS SD in patients 1p loss and no 1p loss, 62% +/- 13% and 87% +/- 3%, respectively; P = .019) but not OS (5-year OS +/- SD, 92% +/- 8% and 97% +/- 2%, respectively). In patients >= 18 months, only SCAs led to relapse and death, with 11q loss as the strongest marker (11q loss and no 11q loss: 5-year EFS +/- SD, 48% +/- 16% and 85% +/- 7%, P = .033; 5-year OS +/- SD, 46% +/- 22% and 92% +/- 6%, P = .038).CONCLUSIONGenomic aberrations of resectable non-MYCN-amplified stage 2 neuroblastomas have a distinct age-dependent prognostic impact. Chromosome 1p loss is a risk factor for relapse but not for diminished OS in patients < 18 months, SCAs (especially 11q loss) are risk factors for reduced EFS and OS in those > 18months. In older patients with SCA, a randomized trial of postoperative chemotherapy compared with observation alone may be indicated.
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- Gadner, H, et al.
(författare)
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Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification
- 2008
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 111:5, s. 2556-2562
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Tidskriftsartikel (refereegranskat)abstract
- Multisystem Langerhans cell histiocytosis (MS-LCH) is associated with high mortality when patients have risk organ involvement (RO+) or are younger than 2 years. In an international randomized trial, LCH-II, we intensified their treatment: arm A consisted of 6 weeks of daily prednisone and weekly vinblastine followed by 18 weeks of daily 6-mercaptopurine with vinblastine/prednisone pulses; etoposide was added in arm B. Considering all 193 randomized risk patients, there were similar outcomes: rapid (6 weeks) response (arm A vs arm B: 63%/71%), 5-year survival probability (74%/79%), disease reactivation frequency (46%/46%), and permanent consequences (43%/37%). However, (1) patients younger than 2 years without RO involvement (RO−) had 100% survival and uniformly high (> 80%) rapid response, (2) RO+ patients not responding within 6 weeks had highest mortality, and (3) importantly, the more intensive arm B reduced mortality in RO+ patients (relative hazard rate, accounting for differences in risk organ involvement, of 0.54; 95% CI = 0.29-1.00). Finally, comparison of RO+ patients in LCH-I and LCH-II confirmed that increasing treatment intensity increased rapid responses (from 43% in arm A LCH-I to 68% in arm B LCH-II; P = .027) and reduced mortality (from 44% in arm A LCH-I to 27% in arm B LCH-II; P = .042). We conclude that intensified treatment significantly increases rapid response and reduces mortality in risk MS-LCH. This trial was registered at http://www.controlled-trials.com as no. ISRCTN57679341.
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