Systemic chemotherapy of pediatric recurrent ependymomas: results from the German HIT-REZ studies

Abstract Purpose Survival in recurrent ependymoma (EPN) depends mainly on the extent of resection achieved. When complete resection is not feasible, chemotherapy is often used to extend progression-free and overall survival. However, no consistent effect of chemotherapy on survival has been found in patients with recurrent EPN. Methods Systemic chemotherapeutic treatment of 138 patients enrolled in the German HIT-REZ-studies was analyzed. Survival depending on the use of chemotherapy, disease-stabilization rates (RR), duration of response (DOR) and time to progression (TTP) were estimated. Results Median age at first recurrence was 7.6 years (IQR: 4.0–13.6). At first recurrence, median PFS and OS were 15.3 (CI 13.3–20.0) and 36.9 months (CI 29.7–53.4), respectively. The Hazard Ratio for the use of chemotherapy in local recurrences in a time-dependent Cox-regression analysis was 0.99 (CI 0.74–1.33). Evaluable responses for 140 applied chemotherapies were analyzed, of which sirolimus showed the best RR (50%) and longest median TTP [11.51 (CI 3.98; 14.0) months] in nine patients, with the strongest impact found when sirolimus was used as a monotherapy. Seven patients with progression-free survival > 12 months after subtotal/no-resection facilitated by chemotherapy were found. No definitive survival advantage for any drug in a specific molecularly defined EPN type was found. Conclusion No survival advantage for the general use of chemotherapy in recurrent EPN was found. In cases with incomplete resection, chemotherapy was able to extend survival in individual cases. Sirolimus showed the best RR, DOR and TTP out of all drugs analyzed and may warrant further investigation.

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The Role of Surgery in IDH-Wild-Type Lower-Grade Gliomas: Threshold at a High Extent of Resection Should be Pursued

Neurosurgery ◽

10.1093/neuros/nyab052 ◽

2021 ◽

Author(s):

Peng Wang ◽

Chen Luo ◽

Peng-jie Hong ◽

Wen-ting Rui ◽

Shuai Wu

Keyword(s):

Cox Regression ◽

Progression Free Survival ◽

Extent Of Resection ◽

Lower Grade ◽

Wild Type ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Lower Grade Glioma ◽

Clinical Benefits

Abstract BACKGROUND While maximizing extent of resection (EOR) is associated with longer survival in lower-grade glioma (LGG) patients, the number of cases remains insufficient in determining a EOR threshold to elucidate the clinical benefits, especially in IDH-wild-type LGG patients. OBJECTIVE To identify the effects of EOR on the survival outcomes of IDH-wild-type LGG patients. METHODS IDH-wild-type LGG patients were retrospectively reviewed. The effect of EOR and other predictor variables on overall survival (OS) and progression-free survival (PFS) was analyzed using Cox regression models and the Kaplan-Meier method. RESULTS A total of 94 patients (median OS: 48.9 mo; median follow-up: 30.6 mo) were included in this study. In the multivariable Cox regression analysis, postoperative residual volume was associated with prolonged OS (HR = 2.238; 95% confidence interval [CI], 1.130-4.435; P = .021) and PFS (HR = 2.075; 95% CI, 1.113-3.869; P = .022). Thresholds at a minimum EOR of 97.0% or a maximum residue of 3.0 cm3 were necessary to impact OS positively. For the telomerase reverse transcriptase (TERT)p-wild-type group, such an association was absent. Significant differences in survival existed between the TERTp-wild-type and mutant patients who underwent relatively incomplete resections (residual ≥2.0 cm3 + TERTp wild type: median OS of 62.6 mo [95% CI: 39.7-85.5 mo]; residual ≥2.0 cm3 + TERTp mutant: median OS of 20.0 mo [95% CI:14.6-25.4 mo]). CONCLUSION Our results support the core role of maximal safe resection in the treatment of IDH-wild-type LGGs, especially for IDH-wild-type + TERTp-mutant LGGs. Importantly, the survival benefits of surgery could only be elucidated at a high EOR cut-off point.

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Myocardial Metabolic Response Predicts Chemotherapy Curative Potential on Hodgkin Lymphoma: A Proof-of-Concept Study

Biomedicines ◽

10.3390/biomedicines9080971 ◽

2021 ◽

Vol 9 (8) ◽

pp. 971

Author(s):

Cecilia Marini ◽

Matteo Bauckneht ◽

Anna Borra ◽

Rita Lai ◽

Maria Isabella Donegani ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Cox Regression ◽

Metabolic Response ◽

Progression Free Survival ◽

Disease Relapse ◽

Cox Regression Analysis ◽

Normal Tissues ◽

Pet Ct ◽

Genome Sharing

Genome sharing between cancer and normal tissues might imply a similar susceptibility to chemotherapy toxicity. The present study aimed to investigate whether curative potential of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) is predicted by the metabolic response of normal tissues in patients with Hodgkin lymphoma (HL). METHODS: According to current guidelines, 86 patients with advanced-stage (IIB-IVB) HL, prospectively enrolled in the HD0607 trial (NCT00795613), underwent 18 F-fluorodeoyglucose PET/CT imaging at diagnosis and, at interim, after two ABVD courses, to decide regimen maintenance or its escalation. In both scans, myocardial FDG uptake was binarized according to its median value. Death and disease relapse were recorded to estimate progression-free survival (PFS) during a follow-up with median duration of 43.8 months (range 6.97–60). RESULTS: Four patients (4.6%) died, while six experienced disease relapse (7%). Complete switch-off of cancer lesions and cardiac lighting predicted a favorable outcome at Kaplan–Mayer analyses. The independent nature and additive predictive value of their risk prediction were confirmed by the multivariate Cox regression analysis. CONCLUSION: Susceptibility of HL lesions to chemotherapy is at least partially determined by factors featuring the host who developed it.

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Clinical relevance of kallikrein-related peptidase 6 (KLK6) and 8 (KLK8) mRNA expression in advanced serous ovarian cancer

Biological Chemistry ◽

10.1515/hsz-2016-0177 ◽

2016 ◽

Vol 397 (12) ◽

pp. 1265-1276 ◽

Cited By ~ 14

Author(s):

Nancy Ahmed ◽

Julia Dorn ◽

Rudolf Napieralski ◽

Enken Drecoll ◽

Matthias Kotzsch ◽

...

Keyword(s):

Ovarian Cancer ◽

Mrna Expression ◽

Cox Regression ◽

Multivariable Analysis ◽

Progression Free Survival ◽

Predictive Marker ◽

Residual Tumor ◽

Mrna Levels ◽

Serous Ovarian Cancer ◽

Cox Regression Analysis

Abstract Most members of the kallikrein-related peptidase family have been demonstrated to be dysregulated in ovarian cancer and modulate tumor growth, migration, invasion, and resistance to chemotherapy. In the present study, we assessed the mRNA expression levels of KLK6 and KLK8 by quantitative PCR in 100 patients with advanced serous ovarian cancer FIGO stage III/IV. A pronounced correlation between KLK6 and KLK8 mRNA expression (rs = 0.636, p < 0.001) was observed, indicating coordinate expression of both peptidases. No significant associations of clinical parameters with KLK6, KLK8, and a combined score KLK6+KLK8 were found. In univariate Cox regression analysis, elevated mRNA levels of KLK6 were significantly linked with shortened overall survival (OS) (hazard ratio [HR] = 2.07, p = 0.007). While KLK8 values were not associated with patients’ outcome, high KLK6+KLK8 values were significantly associated with shorter progression-free survival (HR = 1.82, p = 0.047) and showed a trend towards significance in the case of OS (HR = 1.82, p = 0.053). Strikingly, in multivariable analysis, elevated KLK6 mRNA values, apart from residual tumor mass, remained an independent predictive marker for poor OS (HR = 2.33, p = 0.005). As KLK6 mRNA and protein levels correlate, KLK6 may represent an attractive therapeutic target for potent and specific inhibitors of its enzymatic activity.

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High expression of fibroblast activation protein (FAP) predicts poor outcome in high-grade serous ovarian cancer

BMC Cancer ◽

10.1186/s12885-020-07541-6 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Min Li ◽

Xue Cheng ◽

Rong Rong ◽

Yan Gao ◽

Xiuwu Tang ◽

...

Keyword(s):

Ovarian Cancer ◽

Cox Regression ◽

Paraffin Section ◽

Progression Free Survival ◽

High Grade ◽

Serous Ovarian Cancer ◽

Systematic Analysis ◽

Cox Regression Analysis ◽

Genes Expression ◽

High Level

Abstract Background High-grade serous ovarian cancer (HGSOC) is a fatal form of ovarian cancer. Previous studies indicated some potential biomarkers for clinical evaluation of HGSOC prognosis. However, there is a lack of systematic analysis of different expression genes (DEGs) to screen and detect significant biomarkers of HGSOC. Methods TCGA database was conducted to analyze relevant genes expression in HGSOC. Outcomes of candidate genes expression, including overall survival (OS) and progression-free survival (PFS), were calculated by Cox regression analysis for hazard rates (HR). Histopathological investigation of the identified genes was carried out in 151 Chinese HGSOC patients to validate gene expression in different stages of HGSOC. Results Of all 57,331 genes that were analyzed, FAP was identified as the only novel gene that significantly contributed to both OS and PFS of HGSOC. In addition, FAP had a consistent expression profile between carcinoma-paracarcinoma and early-advanced stages of HGSOC. Immunological tests in paraffin section also confirmed that up-regulation of FAP was present in advanced stage HGSOC patients. Prediction of FAP network association suggested that FN1 could be a potential downstream gene which further influenced HGSOC survival. Conclusions High-level expression of FAP was associated with poor prognosis of HGSOC via FN1 pathway.

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Predictors of tumor progression among children with gangliogliomas

Journal of Neurosurgery Pediatrics ◽

10.3171/2009.2.peds0861 ◽

2009 ◽

Vol 3 (6) ◽

pp. 461-466 ◽

Cited By ~ 25

Author(s):

Mostafa El Khashab ◽

Lynn Gargan ◽

Linda Margraf ◽

Korgun Koral ◽

Farideh Nejat ◽

...

Keyword(s):

Risk Factors ◽

Tumor Progression ◽

Cox Regression ◽

Tumor Resection ◽

Progression Free Survival ◽

Initial Presentation ◽

Subtotal Resection ◽

Low Grade ◽

Cox Regression Analysis ◽

Presenting Symptoms

Object Few reports describe the outcome and prognostic factors for children with gangliogliomas. The objective of this report was to describe the progression-free survival (PFS) for children with low-grade gangliogliomas and identify risk factors for tumor progression. Methods A retrospective study was performed in children with low-grade gangliogliomas who were evaluated and treated in the neuro-oncology department between 1986 and 2006 to determine risk factors for subsequent tumor progression. Results A total of 38 children with newly diagnosed gangliogliomas were included in this report. Thirty-four children were treated with surgery alone, 3 with subtotal resection and radiation therapy, and 1 with subtotal resection and chemotherapy. The follow-up ranged from 4 months to 15.8 years (mean 5.7 ± 4.2 years [± SD]). Seven children have experienced tumor progression, and 1 child died after his tumor subsequently underwent malignant transformation. The 5-year PFS was calculated to be 81.2% using Kaplan-Meier survival analysis. Initial presentation with seizures (p = 0.004), tumor location in the cerebral hemisphere (p = 0.020), and complete tumor resection (p = 0.035) were associated with prolonged PFS. Further analysis of the above significant variables by a Cox regression model identified initial presentation with seizures as being associated with prolonged PFS (p = 0.028). Conclusions The PFS and overall survival of children with gangliogliomas are good. Tumors located in the cerebral hemispheres, the achievement of total resection, and seizures at presentation were associated with prolonged PFS. Cox regression analysis identified presenting symptoms including seizures as significant predictive factors of PFS. Prospective studies with larger numbers of children are needed to define the significant factors of tumor progression.

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Short-term outcomes associated with temozolomide or PCV chemotherapy for 1p/19q-codeleted WHO grade 3 oligodendrogliomas: a national evaluation

Neuro-Oncology Practice ◽

10.1093/nop/npac004 ◽

2022 ◽

Author(s):

Nayan Lamba ◽

Malia McAvoy ◽

Vasileios K Kavouridis ◽

Timothy R Smith ◽

Mehdi Touat ◽

...

Keyword(s):

Cox Regression ◽

Extent Of Resection ◽

First Line ◽

Short Term ◽

Who Grade ◽

Cox Regression Analysis ◽

Significant Difference ◽

Pcv Chemotherapy ◽

Grade 3 ◽

National Analysis

Abstract Background The optimal chemotherapy regimen between temozolomide and procarbazine, lomustine, and vincristine (PCV) remains uncertain for W.H.O. grade 3 oligodendroglioma (Olig3) patients. We therefore investigated this question using national data. Methods Patients diagnosed with radiotherapy-treated 1p/19q-codeleted Olig3 between 2010-2018 were identified from the National Cancer Database. The OS associated with first-line single-agent temozolomide vs. multi-agent PCV was estimated by Kaplan-Meier techniques and evaluated by multivariable Cox regression. Results 1,596 radiotherapy-treated 1p/19q-codeleted Olig3 patients were identified: 88.6% (n=1,414) treated with temozolomide and 11.4% (n=182) with PCV (from 5.4% in 2010 to 12.0% in 2018) in the first-line setting. The median follow-up was 35.5 months (interquartile range [IQR] 20.7-60.6 months) with 63.3% of patients alive at time of analysis. There was a significant difference in unadjusted OS between temozolomide (5yr-OS 58.9%, 95%CI: 55.6-62.0) and PCV (5yr-OS 65.1%, 95%CI: 54.8-73.5; p=0.04). However, a significant OS difference between temozolomide and PCV was not observed in the Cox regression analysis adjusted by age and extent of resection (PCV vs. temozolomide HR 0.81, 95%CI: 0.59-1.11, p=0.18). PCV was more frequently used for younger Olig3s, but otherwise was not associated with patient’s insurance status or care setting. Conclusions In a national analysis of Olig3s, first-line PCV chemotherapy was associated with a slightly improved unadjusted short-term OS compared to temozolomide; but not following adjustment by patient age and extent of resection. There has been an increase in PCV utilization since 2010. These findings provide preliminary data while we await the definitive results from the CODEL trial.

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Association between prior radical surgery (RS) and outcomes with immune checkpoint inhibitor (ICI) therapy for advanced urothelial carcinoma (aUC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.444 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 444-444

Author(s):

Dimitrios Makrakis ◽

Daniel Castellano ◽

Ivan de Kouchkovsky ◽

Joseph J. Park ◽

Mehmet Asim Bilen ◽

...

Keyword(s):

Immune Checkpoint Inhibitor ◽

Overall Response Rate ◽

Cox Regression ◽

Progression Free Survival ◽

Similar Proportion ◽

Multivariable Model ◽

Free Survival ◽

Cox Regression Analysis ◽

Response Table ◽

Advanced Urothelial Carcinoma

444 Background: It is unclear whether prior RS of primary tumor is associated with response and outcomes with ICI in aUC. We hypothesized that such response and outcomes would not differ based on prior RS. Methods: We performed a retrospective cohort study including patients (pts) with aUC who received ICI. We compared overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) between pts with vs without RS [cystectomy or (nephro)-ureterectomy]. Analysis was stratified based on ICI therapy line (first-line vs salvage). A separate comparison between pts with prior RS or radiation (RT) only or none was also pursued. ORR was compared between groups using logistic regression, as well OS and PFS using cox regression analysis; a multivariable model was built adjusting for calculated Bellmunt score. P<0.05 was significant. Results: We identified 984 pts from 24 institutions; 682, 704 and 673 were included in OS, PFS and ORR analyses, respectively; 54% of pts had prior RS with median age 68 at ICI initiation with RS vs 71 without RS with similar proportion of men (73-74%) and ever smokers (70-71%). The RS group had higher proportion (%) of white pts (77% vs 71%), lower % of pts with Hb<10g/dL at ICI initiation (23% vs 32%) but not significantly higher % of liver metastasis at ICI initiation (23% vs 17%). Bellmunt score with vs without RS was 16% vs 11%, 50% vs 48%, 27% vs 37%, 7% vs 4% for 0, 1, 2, and 3, respectively. ORR and PFS were not significantly different between groups, while prior RS was associated with longer OS (unadjusted HR 0.8, p=0.03). However, after adjustment for Bellmunt score, this association was not significant (table). Upon stratification based on treatment line, OS was longer with prior RS (0.7, p=0.03) for those treated with salvage ICI but this was not significant after adjusting for Bellmunt score. ORR, PFS and OS were not significantly different between pts receiving prior RT only vs RS vs none. Conclusions: Prior RS was not significantly associated with longer OS in pts with aUC receiving ICI after adjusting for Bellmunt score. Further work is needed to interrogate tumor-host immune interactions and identify biomarkers that can be prognostic and/or predictive of ICI response. [Table: see text]

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The Role of Extent of Resection in IDH1 Wild-Type or Mutant Low-Grade Gliomas

Neurosurgery ◽

10.1093/neuros/nyx265 ◽

2017 ◽

Vol 82 (6) ◽

pp. 808-814 ◽

Cited By ~ 20

Author(s):

Toral Patel ◽

Evan D Bander ◽

Rachael A Venn ◽

Tiffany Powell ◽

Gustav Young-Min Cederquist ◽

...

Keyword(s):

Cox Regression ◽

Extent Of Resection ◽

World Health ◽

Low Grade ◽

Wild Type ◽

Who Grade ◽

Cox Regression Analysis ◽

Low Grade Gliomas ◽

Grade Ii ◽

The Impact

Abstract BACKGROUND Maximizing extent of resection (EOR) improves outcomes in adults with World Health Organization (WHO) grade II low-grade gliomas (LGG). However, recent studies demonstrate that LGGs bearing a mutation in the isocitrate dehydrogenase 1 (IDH1) gene are a distinct molecular and clinical entity. It remains unclear whether maximizing EOR confers an equivalent clinical benefit in IDH mutated (mtIDH) and IDH wild-type (wtIDH) LGGs. OBJECTIVE To assess the impact of EOR on malignant progression-free survival (MPFS) and overall survival (OS) in mtIDH and wtIDH LGGs. METHODS We performed a retrospective review of 74 patients with WHO grade II gliomas and known IDH mutational status undergoing resection at a single institution. EOR was assessed with quantitative 3-dimensional volumetric analysis. The effect of predictor variables on MPFS and OS was analyzed with Cox regression models and the Kaplan–Meier method. RESULTS Fifty-two (70%) mtIDH patients and 22 (30%) wtIDH patients were included. Median preoperative tumor volume was 37.4 cm3; median EOR of 57.6% was achieved. Univariate Cox regression analysis confirmed EOR as a prognostic factor for the entire cohort. However, stratifying by IDH status demonstrates that greater EOR independently prolonged MPFS and OS for wtIDH patients (hazard ratio [HR] = 0.002 [95% confidence interval {CI} 0.000-0.074] and HR = 0.001 [95% CI 0.00-0.108], respectively), but not for mtIDH patients (HR = 0.84 [95% CI 0.17-4.13] and HR = 2.99 [95% CI 0.15-61.66], respectively). CONCLUSION Increasing EOR confers oncologic and survival benefits in IDH1 wtLGGs, but the impact on IDH1 mtLGGs requires further study.

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The predictive value of MAP2K1/2 mutations for efficiency of immunotherapy in melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e21587 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e21587-e21587

Author(s):

Ting Ye ◽

Jieying Zhang ◽

Xinyi Liu ◽

Mengmei Yang ◽

Yuhan Zhou ◽

...

Keyword(s):

Overall Survival ◽

Predictive Value ◽

Cox Regression ◽

Treatment Options ◽

Objective Response ◽

Progression Free Survival ◽

Driver Mutations ◽

Cox Regression Analysis ◽

Melanoma Patients ◽

The Impact

e21587 Background: Immunotherapies targeting immune checkpoint receptors have become the cornerstone of systemic treatment options for malignant melanoma. The response to these immunotherapies may correlate with driver mutations. MAP2K1/2 genes are mutated in approximately 10% of melanomas, however, the impact of MAP2K1/2 gene alterations on the efficiency of immunotherapy has not been clarified. Methods: Six metastatic melanoma clinical cohorts treated with ICIs were included to investigate the association between clinical efficacy of immunotherapy and MAP2K1/2 mutations. Survival analyses were conducted in cohorts receiving two kinds of ICB agents, namely anti-CTLA-4 or anti-PD-1. RNA expression profiling from these cohorts and from the TCGA melanoma cohort were used to explore the potential mechanism related to immune activation. Results: In an independent anti-CTLA-4-treated cohort (n = 110), we found that MAP2K1/2 mutations are predictive of high objective response rate (17.6% vs 1.3%, p = 0.0185) and long progression-free survival [median OS, 49.2 months vs 8.3 months; hazard ratio (HR) = 0.37; 95% CI, 0.15–0.91; p = 0.0307] and overall survival (median PFS, 19.4 months vs 2.8 months; HR = 0.2; 95% CI, 0.05–0.83; p = 0.0262). This predictive value was further validated in a pooled anti-CTLA-4-treated cohort (n = 235) in terms of overall survival (median OS, 49.3 months vs 22.0 months; HR = 0.44; 95% CI, 0.22–0.91; p = 0.0255). However, no correlation between MAP2K1/2 mutations and overall survival was observed in the anti-PD-1-treated cohort (n = 285). Subgroup Cox regression analysis indicated that MAP2K-mutated patients receive less benefit from the anti-PD-1 monotherapy than from the anti-CTLA-4 treatment (median OS, 27.0 months vs 49.3 months; HR = 3.26; 95% CI, 1.18–9.02; p = 0.0225), which was contrary to the result obtained for the total population. Furthermore, transcriptome profiling analysis revealed that MAP2K-mutated tumors are enriched in CD8+ T cells, B cells, and neutrophil cells and also express high levels of CD33 and IL10, which might be the underlying mechanism for melanoma patients with MAP2K1/2-mutated benefit more from anti-CTLA-4 treatment. Conclusions: We identified mutations in MAP2K1/2 genes as the independent predictive factors for anti-CTLA-4 therapy in melanoma patients and found that anti-CTLA-4 treatment in patient harbouring MAP2K1/2 mutations might be more effective than the anti-PD-1 therapy.

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Efficacy of sorafenib in heavily pretreated adult patients with metastatic osteosarcoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e23511 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e23511-e23511

Author(s):

Nail Paksoy ◽

Izzet Dogan ◽

Meltem Ekenel ◽

Mert Basaran

Keyword(s):

Treatment Option ◽

Rare Variants ◽

Cox Regression ◽

Real Life ◽

Palliative Radiotherapy ◽

Progression Free Survival ◽

Adult Patients ◽

Cox Regression Analysis ◽

Metastatic Osteosarcoma ◽

Heavily Pretreated

e23511 Background: Osteosarcoma is a rare tumor and is commonly seen in young people. It arises from bone and rarely from soft tissue. Surgery is the primary treatment option for osteosarcoma. Osteosarcoma is radioresistant, except for rare variants. The choices of chemotherapy are limited in the treatment of metastatic osteosarcoma. The efficiency data of targetted therapies in metastatic osteosarcoma is limited. This study aimed to evaluate sorafenib's efficacy in adult patients with heavily pretreated metastatic osteosarcoma. Methods: We evaluated the patients aged over 18 years with metastatic osteosarcoma retrospectively. The clinical, pathological, and treatment data of the patients were recorded. We used SPSS 25. version for statistical analysis. Kaplan-Meier and Cox-regression analysis were used for survival analysis. Results: Fifteen patients were included in the study. Ten (66.7%) of the patients were male, and the median age was 25 (range,19-64). The primary localization of the tumor was the lower extremity (53.4%), head and neck (20%), upper extremity (13.3%), and other sites (13.3%), respectively. The most common metastatic sites were lung (93.3%), bone (46.7%,) and other (33.3%), respectively. Before sorafenib, fourteen (93.3%) patients had received at least two different cytotoxic chemotherapy regimens, six (40%) patients palliative radiotherapy. In addition, metastasectomy had performed on eight (53.3%) patients. The median progression-free survival was 5.5 (95% CI, 1.3-9.7) months with sorafenib. The stable response was observed in 8 (50%) patients and progressive disease 8 (50%) patients. Grade 1-2 toxicities were observed in 50% of the patients, and grade 3-4 toxicities in 14.3% of the patients. Conclusions: In the study, we showed real-life outcomes of sorafenib for disease control in heavily pretreated adult patients with metastatic osteosarcoma. Sorafenib was effective and well-tolerated in the patients. Sorafenib may be considered as a treatment option after chemotherapy in patients with metastatic osteosarcoma.

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