Superior Survival in Treatment of Primary Nonmetastatic Pediatric Osteosarcoma of the Extremity

Wilkins, Ross M.; Cullen, John W.; Odom, Lorrie F.; Jamroz, Brandt A.; Cullen, Patsy McGuire; Fink, Kyle; Peck, Sanford D.; S, Stevens; Kelly, Cynthia M.; Camozzi, Anne B.

doi:10.1245/aso.2003.03.061

Cited by 80 publications

(40 citation statements)

References 31 publications

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“…Recent studies have demonstrated a more favorable outcome, especially for patients with nonmetastatic osteosarcoma 5, 6. Five‐year survival rates of 60% to 80% have been reported for patients receiving intensive multidrug chemotherapy and surgery for aggressive local control 5, 6, 7, 8, 9, 10, 11. However, despite the recent improvement in survival, a substantial number of patients still develop metastases or suffer tumor‐related death, so more accurate identification of patient subgroups with different levels of risk is substantially important.…”

Section: Introductionmentioning

confidence: 99%

Development and external validation of nomograms predicting distant metastases and overall survival after neoadjuvant chemotherapy and surgery for patients with nonmetastatic osteosarcoma: A multi‐institutional study

Ogura

Fujiwara

Yasunaga

et al. 2015

Cancer

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BACKGROUNDIn this era of individualized cancer treatment, data that could be applied to predicting the survival of patients with osteosarcoma are still limited because of the rarity of the disease and the difficulty in accumulating a sufficient number of patients. Therefore, a multi‐institutional collaboration was implemented to develop and externally validate nomograms that would predict metastasis‐free survival (MFS) and overall survival (OAS) for patients with nonmetastatic osteosarcoma.METHODSThis study retrospectively examined 1070 patients treated with neoadjuvant chemotherapy and surgery for nonmetastatic osteosarcoma. Data from Japanese patients (n = 557) were used to develop multivariate nomograms based on Cox regression. Six clinical and pathologic variables were built into nomograms estimating the probability of MFS and OAS 3 and 5 years after diagnosis. The model was internally validated for discrimination and calibration with bootstrap resampling and was externally validated with an independent patient cohort from Korea (n = 513).RESULTSA patient's age, tumor site, and histologic response were found to have a stronger influence on MFS and OAS in the model than sex, tumor size, or pathologic fracture. The nomograms and calibration plots based on these results well predicted the probability of MFS (concordance index, 0.631) and OAS (concordance index, 0.679). The concordance indices for external validation were 0.682 for MFS and 0.665 for OAS.CONCLUSIONSThe nomograms were externally validated and verified to be useful for the prediction of MFS and OAS and for the assessment of the postoperative prognosis. They can be used for counseling patients and for establishing appropriate surveillance strategies after surgery. Cancer 2015;121:3844–3852. © 2015 American Cancer Society.

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Section: Introductionmentioning

confidence: 99%

Development and external validation of nomograms predicting distant metastases and overall survival after neoadjuvant chemotherapy and surgery for patients with nonmetastatic osteosarcoma: A multi‐institutional study

Ogura

Fujiwara

Yasunaga

et al. 2015

Cancer

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“…50 Although data focusing on the spine are scant, it is notable that the addition of chemotherapy to wide surgical excision in appendicular osteosarcoma has greatly increased survival. 36,37,39,40,42,49,51,55,64 Importantly, a large study by Link et al demonstrated that patients undergoing surgery only had a 2-year relapse-free survival rate of 17% versus 66% in the adjuvant chemotherapy group among 36 randomized patients, which was further supported by similar results in 77 patients who refused randomization. 37 Gherlinzoni et al further found that the incidence of local recurrence was related above all to adjuvant chemotherapy-induced tumor necrosis.…”

Section: Discussionmentioning

confidence: 87%

Osteosarcoma of the spine: prognostic variables for local recurrence and overall survival, a multicenter ambispective study

Dekutoski

Clarke²,

Rose

et al. 2016

SPI

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OBJECTIVE Primary spinal osteosarcomas are rare and aggressive neoplasms. Poor outcomes can occur, as obtaining marginal margins is technically demanding; further Enneking-appropriate en bloc resection can have significant morbidity. The goal of this study is to identify prognostic variables for local recurrence and mortality in surgically treated patients diagnosed with a primary osteosarcoma of the spine. METHODS A multicenter ambispective database of surgically treated patients with primary spine osteosarcomas was developed by AOSpine Knowledge Forum Tumor. Patient demographic, diagnosis, treatment, perioperative morbidity, local recurrence, and cross-sectional survival data were collected. Tumors were classified in 2 cohorts: Enneking appropriate (EA) and Enneking inappropriate (EI), as defined by pathology margin matching Enneking-recommended surgical margins. Prognostic variables were analyzed in reference to local recurrence and survival. RESULTS Between 1987 and 2012, 58 patients (32 female patients) underwent surgical treatment for primary spinal osteosarcoma. Patients were followed for a mean period of 3.5 ± 3.5 years (range 0.5 days to 14.3 years). The median survival for the entire cohort was 6.7 years postoperative. Twenty-four (41%) patients died, and 17 (30%) patients suffered a local recurrence, 10 (59%) of whom died. Twenty-nine (53%) patients underwent EA resection while 26 (47%) patients underwent EI resection with a postoperative median survival of 6.8 and 3.7 years, respectively (p = 0.048). EI patients had a higher rate of local recurrence than EA patients (p = 0.001). Patient age, previous surgery, biopsy type, tumor size, spine level, and chemotherapy timing did not significantly influence recurrence and survival. CONCLUSIONS Osteosarcoma of the spine presents a significant challenge, and most patients die in spite of aggressive surgery. There is a significant decrease in recurrence and an increase in survival with en bloc resection (EA) when compared with intralesional resection (EI). The effect of adjuvant and neoadjuvant chemotherapeutics, as well as method of biopsy, requires further exploration.

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“…17 The highest response rate (approximately 81%) was reported for the most part in a pediatric population. 18 Chemotherapy-related toxicities in previous studies have been reported as Grade 3-4 nausea and emesis and myelosuppression and the majority subside with supportive therapy. 14,15 The toxicities reported in the T10, T12, COSS-80, COSS-82, and OS-2 protocols are similar, with myelotoxicity being the most commonly reported toxicity.…”

Section: Discussionmentioning

confidence: 98%

The feasibility of neoadjuvant high‐dose chemotherapy and autologous peripheral blood stem cell transplantation in patients with nonmetastatic high grade localized osteosarcoma

Arpacı

Ataergin

Özet

et al. 2005

Cancer

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BACKGROUNDThe primary and secondary objectives of the current study were to improve the ≥ 90% tumor necrosis rate and assess the toxicity profile of the neoadjuvant high‐dose chemotherapy (HDC) regimen, respectively.METHODSTwenty‐two patients with AJCC Stage IIB high‐grade osteosarcoma were included in the current study. Two cycles of an induction chemotherapy regimen including cisplatin, doxorubicin, and ifosfamide followed by HDC and autologous peripheral blood stem cell support or transplantation (APBSCT) were given. After engraftment was achieved, the patients underwent limb‐sparing surgery (LSS) followed by three to six cycles of postoperative chemotherapy depending on the tumor necrosis rate.RESULTSThe median follow‐up, the total duration of treatment, and the time to surgery were 23.7 months, 5.96 months, and 3.03 months, respectively. The necrosis rate was at least 90% in 82% of the cases. The 3‐year overall survival (OS) and disease‐free survival (DFS) rates were 83% and 70%, respectively. Leukopenia, anemia, thrombocytopenia, nausea and emesis, and mucositis were the most frequent Grade 3 and Grade 4 toxicities (according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) of induction, high‐dose, and adjuvant chemotherapies. At the time of last follow‐up, no patient had died of chemotherapeutic toxicity. LSS was performed in all patients. Surgery‐related complications were reported in 3 of 22 patients. Functional scoring results were excellent in eight patients, good in nine patients, fair in two patients, and poor in three patients.CONCLUSIONSThe results of the current Phase II study suggest that neoadjuvant HDC provides a greater than 90% necrosis rate with acceptable toxicity. A short duration of therapy and the feasibility of LSS in all patients are additional advantages of this approach. Cancer 2005. © 2005 American Cancer Society.

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Superior Survival in Treatment of Primary Nonmetastatic Pediatric Osteosarcoma of the Extremity

Abstract: This study demonstrates excellent survival with a dose-intensified neoadjuvant protocol. Future endeavors should involve a multi-institutional randomized study comparing this approach with another multiagent intravenous neoadjuvant protocol.

Cited by 80 publications

References 31 publications

Development and external validation of nomograms predicting distant metastases and overall survival after neoadjuvant chemotherapy and surgery for patients with nonmetastatic osteosarcoma: A multi‐institutional study

Development and external validation of nomograms predicting distant metastases and overall survival after neoadjuvant chemotherapy and surgery for patients with nonmetastatic osteosarcoma: A multi‐institutional study

Osteosarcoma of the spine: prognostic variables for local recurrence and overall survival, a multicenter ambispective study

The feasibility of neoadjuvant high‐dose chemotherapy and autologous peripheral blood stem cell transplantation in patients with nonmetastatic high grade localized osteosarcoma

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