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@ARTICLE{Hoberger:307579,
author = {M. Hoberger and R. L. Zuber and A. Burkhard-Meier and D. Di
Gioia and V. Jurinovic and M. Völkl and S. E. Güler and M.
Albertsmeier and A. Klein and H. R. Dürr and N.-S.
Schmidt-Hegemann and T. Knösel and W. G. Kunz and M. von
Bergwelt-Baildon$^*$ and L. H. Lindner and L. M.
Berclaz$^*$},
title = {{L}ong-term benefit from high-dose ifosfamide in sarcoma
depends on sustained prior control and timely intervention:
a machine learning analysis.},
journal = {Journal of cancer research and clinical oncology},
volume = {152},
number = {1},
issn = {0301-1585},
address = {Heidelberg},
publisher = {Springer},
reportid = {DKFZ-2026-00074},
pages = {34},
year = {2026},
note = {#DKTKZFB9#},
abstract = {High-dose ifosfamide (HD-IFO) remains an effective regimen
for advanced bone and soft tissue sarcomas, but predictors
of long-term benefit are poorly defined. This study
evaluated clinical outcomes and prognostic factors using
machine learning-assisted modeling in sarcoma patients
treated with HD-IFO at a high-volume academic center.We
retrospectively analyzed 26 patients with histologically
confirmed bone or soft tissue sarcoma who received HD-IFO
(≥ 12 g/m2 per cycle) between 2015 and 2025.
Progression-free survival (PFS) and overall survival (OS)
were estimated by the Kaplan-Meier method and compared
across RECIST response categories using log-rank testing.
Prognostic factors were identified using Least Absolute
Shrinkage and Selection Operator (LASSO) logistic regression
with leave-one-out cross-validation. The top three variables
were entered into multivariable logistic regression to
estimate odds ratios (ORs) for OS > 24 months.Median PFS and
OS from start of HD-IFO was 6.6 months $(95\%$ CI 4.4-9.8)
and 24.7 months $(95\%$ CI, 14.7-34.2), respectively.
Patients with progressive disease (PD) had significantly
shorter OS than those with partial response (PR; p = 0.0047)
or stable disease (SD; p = 0.0485). LASSO identified
intervention prior to progression, prior tumor control ≥
12 months, and absence of metastases as the strongest
predictors for OS > 24 months. In multivariable analysis,
intervention prior to progression (OR 24.18, $95\%$ CI
1.81-1001.27, p = 0.037) and prior tumor control ≥ 12
months (OR 25.39, $95\%$ CI 2.1-1008.9, p = 0.030)
independently predicted OS > 24 months.HD-IFO provides
durable disease control in selected sarcoma patients,
particularly those with sustained prior tumor control and
intervention prior to progression.},
keywords = {Humans / Ifosfamide: administration $\&$ dosage /
Ifosfamide: therapeutic use / Female / Male / Machine
Learning / Middle Aged / Retrospective Studies / Sarcoma:
drug therapy / Sarcoma: pathology / Sarcoma: mortality /
Adult / Antineoplastic Agents, Alkylating: administration
$\&$ dosage / Antineoplastic Agents, Alkylating: therapeutic
use / Aged / Young Adult / Prognosis / Bone Neoplasms: drug
therapy / Bone Neoplasms: pathology / Bone Neoplasms:
mortality / Adolescent / Bone sarcoma (Other) / High-dose
ifosfamide (Other) / Machine learning-assisted modeling
(Other) / Soft tissue sarcoma (Other) / Ifosfamide (NLM
Chemicals) / Antineoplastic Agents, Alkylating (NLM
Chemicals)},
cin = {MU01},
ddc = {610},
cid = {I:(DE-He78)MU01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41504936},
doi = {10.1007/s00432-025-06410-8},
url = {https://inrepo02.dkfz.de/record/307579},
}