High-dose chemotherapy and autologous stem cell transplantation with melphalan, etoposide and carboplatin for high-risk osteosarcoma

Cr, Hong; Hj, Kang; Ms, Kim; Hy, Ju; Jw, Lee; Kim, Ho; Hs, Kim; Park, Sang Hoon; Kd, Park; Jd, Park; Hy, Shin; Ahn, Hyo Hyun

doi:10.1038/bmt.2015.145

Cited by 15 publications

(14 citation statements)

References 13 publications

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“…Currently, commonly used agents for treating osteosarcoma include methotrexate (MTX), doxorubicin, cisplatin and ifosfamide [25], [26]. High-dose chemotherapy is being applied to metastatic patients, but their side effects also increase [6], [27], [28]. Therefore, the dose of chemotherapy for treating metastatic patients should be carefully considered.…”

Section: Discussionmentioning

confidence: 99%

Risk and clinicopathological features of osteosarcoma metastasis to the lung: A population-based study

Huang

Zhao

Bai

et al. 2019

Journal of Bone Oncology

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BackgroundOsteosarcoma is the most common primary sarcoma of the bone. Lung osteosarcoma metastases at diagnosis have a significantly poor prognosis, even when surgery plus chemotherapy are performed. Our goal was to analyze clinical and sarcoma characteristics that could help identify factors related to an increased rate of lung metastasis and to identify different modes of treatment and its correlation with survival.Materials and MethodsThe Surveillance, Epidemiology, and End Results (SEER) database was used to identify all osteosarcoma patients diagnosed from 2010 to 2015. Patient characteristics such as age, sex, ethnicity, marital status, tumor location, histologic grade, surgery, chemotherapy, radiation therapy, SEER cause-specific death classification, survival, and lung metastasis were collected. These factors were analyzed using Univariate and multivariate regression models in survival analyses.ResultsA total of 1057 osteosarcoma patients diagnosed from 2010 to 2015 were included, of which 176 were patients with lung metastasis. Substantial disparities in the rate of lung metastasis existed when osteosarcoma patients were stratified according to tumor location (P = 0.0002) and tumor size (P < .001). Using a Multivariate Cox regression model, being older than 30 years (vs. younger than 30, HR = 2.171, 95% CI = 1.623–2.905, P < .0001), having a tumor >5–10 cm (vs. <5 cm, HR = 2.046, 95% CI = 1.153–3.632, P = 0.0014) and >10 cm (vs. <5 cm, HR = 3.610, 95% CI = 2.066–6.310, P < .0001) were related to an increased HR for all-cause death. The HR decreased in patients with surgery (vs. no surgery, HR = 0.189, 95% CI = 0.138–0.260, P < 0.0001) and osteosarcoma. As for osteosarcoma patients with lung metastases, Multivariate Cox regressions revealed that an increased HR was associated with being older than 30 years (vs. younger than 30 years, HR = 2.142, 95% CI = 1.273–3.605, P = .0041) and married (vs. no marriage, HR = 2.418, 95% CI = 1.400–4.176, P= .0015), while a decreased HR was related to having had surgery (vs. no surgery, HR = 0.282, 95% CI = 0.171–0.464, P < .0001) and chemotherapy (vs. no chemotherapy, HR = 0.107, 95% CI = 0.050–0.229, P < .0001).ConclusionsAdvanced age (older than 30 years) and large tumors were related to a higher risk of lung metastases in osteosarcoma patients. Therefore, patients who were diagnosed at advanced age or had large tumors should receive comprehensive chest CT scans. Surgery and chemotherapy can significantly improve the survival of metastatic patients, while radiotherapy did not improve survival in these patients.

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Section: Discussionmentioning

confidence: 99%

Risk and clinicopathological features of osteosarcoma metastasis to the lung: A population-based study

Huang

Zhao

Bai

et al. 2019

Journal of Bone Oncology

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“…The role of MEC in brain tumors is limited and the protocol is usually included as a part of the tandem HDCT strategy [ 27 ]. MEC HDCT in osteosarcoma did not show any clear advantage, and the megatherapy strategy is considered ineffective in this indication [ 28 ]. Children with unfavorable nephroblastoma diagnoses tolerated MEC very well and good curability rates were observed [ 29 , 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Melphalan, Etoposide, and Carboplatin Megatherapy with Autologous Stem Cell Transplantation in Children with Relapsing or Therapy-Resistant Extracranial Germ-Cell Tumors—A Retrospective Analysis

Ussowicz

Mielcarek‐Siedziuk

Musiał³

et al. 2020

Cancers

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Pediatric germ cell tumors (GCTs) are a group of chemosensitive malignancies with a 90% curability rate. We report a series of children with relapsing or therapy-resistant GCT treated with melphalan–etoposide–carboplatin high-dose chemotherapy (HDCT) and autologous stem cell transplantation. This consisted of 18 children, either with GCTs after relapse (nine patients) or with an unsatisfactory response to first-line chemotherapy (nine patients), who underwent HDCT. The HDCT regimens MEC1 (carboplatin 1500 mg/m2, etoposide 1800 mg/m2, and melphalan 140 mg/m2) and MEC2 (carboplatin 800 mg/m2, etoposide 800 mg/m2, and melphalan 140 mg/m2) were each used in nine patients. The median observation time was 81 months, the 5-year overall survival (OS) was 76%, and the event-free survival (EFS) was 70.8%. Non-relapse mortality was 0%, and four patients died after HDCT due to progression of the malignancy. No difference in OS or EFS was noted between the MEC1 and MEC2 protocols. The 5-year OS and 5-year EFS were higher in children treated with autologous stem cell transplantation before the age of four years. The presence of metastatic disease or time of HDCT consolidation during first/subsequent line chemotherapy did not affect patient survival. The melphalan–etoposide–carboplatin protocol is feasible in pediatric GCT, but is associated with potentially life-threatening complications. In conclusion, the use of HDCT must be examined in well-designed clinical trials, and the identification of patients who can benefit from this approach is critical to avoid overtreatment.

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“…In another study of patients with Ewing tumors ( 23 ), tandem (n = 13) or single (n = 7) HDCT/auto-SCT was performed in 20 patients, yielding OS and EFS rates of 45% and 47%, respectively. For osteosarcoma, Hong et al ( 24 ) reported the result of HDCT/auto-SCT in 19 patients with high-risk osteosarcoma, and the OS and EFS were 78.3% and 67.4%, at a median follow-up of 31 months from HDCT/auto-SCT. In a study of 36 patients with desmoplastic small round cell tumors treated with HDCT/auto-SCT ( 25 ), the 3-year OS was 57% in patients who achieved CR before HDCT/auto-SCT.…”

Section: Discussionmentioning

confidence: 99%

High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Children with High-Risk or Recurrent Bone and Soft Tissue Sarcomas

Choi

Lee

et al. 2016

J Korean Med Sci

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Despite increasing evidence that high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) might improve the survival of patients with high-risk or recurrent solid tumors, therapy effectiveness for bone and soft tissue sarcoma treatment remains unclear. This study retrospectively investigated the feasibility and effectiveness of HDCT/auto-SCT for high-risk or recurrent bone and soft tissue sarcoma. A total of 28 patients (18 high-risk and 10 recurrent) underwent single or tandem HDCT/auto-SCT between October 2004 and September 2014. During follow-up of a median 15.3 months, 18 patients exhibited disease progression and 2 died of treatment-related toxicities (1 veno-occlusive disease and 1 sepsis). Overall, 8 patients remained alive and progression-free. The 3-year overall survival (OS) and event-free survival (EFS) rates for all 28 patients were 28.7% and 26.3%, respectively. In the subgroup analysis, OS and EFS rates were higher in patients with complete or partial remission prior to HDCT/auto-SCT than in those with worse responses (OS, 39.1% vs. 0.0%, P = 0.002; EFS, 36.8% vs. 0.0%, P < 0.001). Therefore, careful selection of patients who can benefit from HDCT/auto-SCT and maximal effort to reduce tumor burden prior to treatment will be important to achieve favorable outcomes in patients with high-risk or recurrent bone and soft tissue sarcomas.

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High-dose chemotherapy and autologous stem cell transplantation with melphalan, etoposide and carboplatin for high-risk osteosarcoma

Cited by 15 publications

References 13 publications

Risk and clinicopathological features of osteosarcoma metastasis to the lung: A population-based study

Risk and clinicopathological features of osteosarcoma metastasis to the lung: A population-based study

Melphalan, Etoposide, and Carboplatin Megatherapy with Autologous Stem Cell Transplantation in Children with Relapsing or Therapy-Resistant Extracranial Germ-Cell Tumors—A Retrospective Analysis

High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Children with High-Risk or Recurrent Bone and Soft Tissue Sarcomas

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