Is It Reasonable for Orthopedic Surgeons to Do Chemotherapy for Patients with High-Grade Bone Sarcoma? A Paradigm for Treatment Individualization

Osteosarcomas (OSs) are a group of neoplasms originating from bone cells, usually presenting in three specific age groups: children, young adults, and the elderly. High-grade OS is an extremely malignant tumor mainly due to evolution into metastatic disease, usually in the lungs. Survival of these patients has improved since the 1980s thanks to close cooperation between oncologists, oncological surgeons and orthopedic surgeons. Unfortunately, no progress has been made in the last 30 years and new, more effective drugs are needed. This article reviews the biological and pharmacological basis of the treatment of OS. Models of clinical pharmacology of the active drugs, toxic effects and reasons for primary and secondary resistance to old and new drugs are discussed.

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Chemotherapy in the Management of Osteosarcoma and Ewing's Sarcoma

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2007.0039 ◽

2007 ◽

Vol 5 (4) ◽

pp. 449-455 ◽

Cited By ~ 11

Author(s):

Scott M. Schuetze

Keyword(s):

Ewing’S Sarcoma ◽

Ewing's Sarcoma ◽

Disease Patient ◽

Bone Sarcoma ◽

The United States ◽

High Grade ◽

Medical Oncologists ◽

Bone Sarcomas ◽

Localized Disease ◽

Relapsed Disease

Sarcomas of bone are rare malignancies diagnosed in fewer than 3000 individuals yearly in the United States. Ewing's sarcoma and most osteosarcoma are high-grade neoplasms and account for approximately one half of bone sarcoma cases. Fewer than 20% of patients presenting with localized Ewing's sarcoma or osteosarcoma are cured with surgery alone. Current management typically involves collaboration among orthopedic oncologists, medical oncologists, musculoskeletal radiologists, sarcoma pathologists, and radiation oncologists. Modern multidisciplinary management of Ewing's sarcoma and osteosarcoma has improved the cure rate of patients with localized disease to more than 50%. Primary chemotherapy for high-grade bone sarcomas often involves intensive, multiagent regimens, and few secondary chemotherapy options are available to treat refractory or relapsed disease. Patient participation in clinical trials of novel therapies for Ewing's sarcoma and osteosarcoma should be strongly encouraged.

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High Long-term Local Control with Sacrectomy for Primary High-grade Bone Sarcoma in Children

Clinical Orthopaedics and Related Research ◽

10.1007/s11999-011-2199-x ◽

2011 ◽

Vol 470 (5) ◽

pp. 1491-1497 ◽

Cited By ~ 10

Author(s):

Alexandre Arkader ◽

Christine H. Yang ◽

Vernon T. Tolo

Keyword(s):

Local Control ◽

Bone Sarcoma ◽

High Grade

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Abstract 3721: Relationship between insulin resistance and chemosensitivity of high grade bone sarcoma

10.1158/1538-7445.am2020-3721 ◽

2020 ◽

Author(s):

Pascaline Boudou-Rouquette ◽

Ithar Gataa ◽

Sixtine De Percin ◽

Camille Tlemsani ◽

David Biau ◽

...

Keyword(s):

Insulin Resistance ◽

Bone Sarcoma ◽

High Grade

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Referral patterns, treatment and outcome of high-grade malignant bone sarcoma in Scandinavia-SSG Central Register 25 years' experience

Journal of Surgical Oncology ◽

10.1002/jso.24074 ◽

2015 ◽

Vol 112 (8) ◽

pp. 853-860 ◽

Cited By ~ 5

Author(s):

Olga Zaikova ◽

Kirsten Sundby Hall ◽

Emelie Styring ◽

Mikael Eriksson ◽

Clement S. Trovik ◽

...

Keyword(s):

Bone Sarcoma ◽

High Grade ◽

Referral Patterns ◽

Central Register

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Time to Treatment Initiation and Survival in Adult Localized High-Grade Bone Sarcoma

Sarcoma ◽

10.1155/2020/2984043 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Joshua M. Lawrenz ◽

Joseph Featherall ◽

Gannon L. Curtis ◽

Jaiben George ◽

Yuxuan Jin ◽

...

Keyword(s):

Overall Survival ◽

Treatment Initiation ◽

Cox Regression ◽

Univariate Analysis ◽

Bone Sarcoma ◽

High Grade ◽

Time To Treatment ◽

Primary Bone Sarcoma ◽

Primary Bone ◽

Time To Treatment Initiation

Objective. Few studies have evaluated the prognostic implication of the length of time from diagnosis to treatment initiation in bone sarcoma. The purpose of this study is to determine if time to treatment initiation (TTI) influences overall survival in adults diagnosed with primary bone sarcoma. Methods. A retrospective analysis of the National Cancer Database identified 2,122 patients who met inclusion criteria with localized, high-grade bone sarcoma diagnosed between 2004 and 2012. TTI was defined as length of time in days from diagnosis to initiation of treatment. Patient, disease-specific, and healthcare-related factors were also assessed for their association with overall survival. Kruskal-Wallis analysis was utilized for univariate analysis, and Cox regression modeling identified covariates associated with overall survival. Results. Any 10-day increase in TTI was not associated with decreased overall survival (hazard ratio (HR) = 1.00; P=0.72). No differences in survival were detected at 1 year, 5 years, and 10 years, when comparing patients with TTI = 14, 30, 60, 90, and 150 days. Decreased survival was significantly associated P<0.05 with patient ages of 51–70 years (HR = 1.66; P=0.004) and > 71 years (HR = 2.89; P<0.001), Charlson/Deyo score ≥2 (HR = 2.02; P<0.001), pelvic tumor site (HR = 1.58; P<0.001), tumor size >8 cm (HR = 1.52; P<0.001), radiation (HR = 1.81; P<0.001) as index treatment, and residing a distance of 51–100 miles from the treatment center (HR = 1.30; P=0.012). Increased survival was significantly associated P<0.05 with chordoma (HR = 0.27; P=0.010), chondrosarcoma (HR = 0.75; P=0.002), treatment at an academic center (HR = 0.64; P=0.039), and a private (HR = 0.67; P=0.006) or Medicare (HR = 0.71; P=0.043) insurer. A transition in care was not associated with a survival disadvantage (HR = 0.90; P=0.14). Conclusions. Longer TTI was not associated with decreased overall survival in localized, high-grade primary bone sarcoma in adults. This is important in counseling patients, who may delay treatment to receive a second opinion or seek referral to a higher volume sarcoma center.

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EURO-B.O.S.S.: A European study on chemotherapy in bone-sarcoma patients aged over 40: Outcome in primary high-grade osteosarcoma

Tumori Journal ◽

10.5301/tj.5000696 ◽

2018 ◽

Vol 104 (1) ◽

pp. 30-36 ◽

Cited By ~ 18

Author(s):

Stefano Ferrari ◽

Stefan S. Bielack ◽

Sigbjørn Smeland ◽

Alessandra Longhi ◽

Gerlinde Egerer ◽

...

Keyword(s):

Present Report ◽

International Study ◽

Bone Sarcoma ◽

Hematological Toxicity ◽

High Grade ◽

Aggressive Approach ◽

Younger Patients ◽

Probability Of Survival ◽

Localized Disease ◽

High Grade Osteosarcoma

Introduction: The EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) was the first prospective international study for patients 41-65 years old with high-grade bone sarcoma treated with an intensive chemotherapy regimen derived from protocols for younger patients with high-grade skeletal osteosarcoma. Methods: Chemotherapy based on doxorubicin, cisplatin, ifosfamide, and methotrexate was suggested, but patients treated with other regimens at the investigators’ choice were also eligible for the study. Results: The present report focuses on the subgroup of 218 patients with primary high-grade osteosarcoma. With a median follow-up of 47 months, the 5-year probability of overall survival (OS) was 66% in patients with localized disease and 22% in case of synchronous metastases. The 5-year OS in patients with localized disease was 29% in pelvic tumors, and 70% and 73% for extremity or craniofacial locations, respectively. In primary chemotherapy, tumor necrosis ≥90% was reported in 21% of the patients. There were no toxic deaths; however, hematological toxicity was considerable with 32% of patients experiencing 1 or more episodes of neutropenic fever. The incidence of nephrotoxicity and neurotoxicity (mainly peripheral) was 28% and 24%, respectively. After methotrexate, 23% of patients experienced delayed excretion, in 4 cases with nephrotoxicity. Conclusions: In patients over 40 years of age with primary high-grade osteosarcoma, an aggressive approach with chemotherapy and surgery can offer the probability of survival similar to that achieved in younger patients. Chemotherapy-related toxicity is significant and generally higher than that reported in younger cohorts of osteosarcoma patients treated with more intensive regimens.

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A European treatment protocol for bone sarcoma in patients older than 40 years

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.10516 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 10516-10516 ◽

Cited By ~ 1

Author(s):

S. Ferrari ◽

S. Smeland ◽

S. Bielack ◽

A. Comandone ◽

P. Dileo ◽

...

Keyword(s):

Complete Remission ◽

Treatment Protocol ◽

International Study ◽

Bone Sarcoma ◽

Poor Responders ◽

High Grade ◽

Dedifferentiated Chondrosarcoma ◽

Peripheral Neurotoxicity ◽

Central Location ◽

Synchronous Metastases

10516 Background: EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.) is the first prospective multicenter international study for patients 41 - 65 years old with high-grade bone sarcoma. Methods: Patients with HG Osteosarcoma (OS), HG sarcoma NOS (S), Fibrosarcoma, MFH, Leiomyosarcoma, Dedifferentiated Chondrosarcoma (DCh) were included. Chemotherapy: Combinations of cisplatin/doxorubicin (CDP 100mg/m2/ADM 60mg/m2), ifosfamide/CDP(IFO 6g/m2/CDP 100mg/m2) and IFO/ADM (IFO 6g/m2/ADM 60mg/m2) were repeated three times (9 cycles). Surgery was planned after 3 cycles. Methotrexate (8g/m2) was postoperatively added in poor responders. Immediate surgery was allowed and 9 cycles with CDP, ADM, IFO were postoperatively given. Results: In December 2007, 140 patients were registered (median age 51 years). OS (51%), S (16%), and DCh (11%) were the more frequent histotypes. Synchronous metastases in 30 (21%) patients, central location of tumor in 45 (32%). Surgical complete remission (SCR) was achieved in 84% of patients, (localized 91%, metastatic 37%) without difference among the histology groups. One surgical-related and one chemotherapy-related death were reported. Grade 4 WBC and PLT incidence was 55% and 17%.Renal toxicity and peripheral neurotoxicity were reported in 16% and 20% of patients. With a median follow-up of 25 months (4–68) 3 year OS was 58% (95%CI 48–68%) [7% (95%CI 0–19%) without SCR]. In patients with SCR, 3 year OS and EFS were 46% (95%CI 9–83%) and 0% in case of synchronous metastases and 69% (95%CI58–80%) and 45% (95%CI33–57%) for localized patients; 50% (95%CI 29–71%) and 40% (95%CI 20–59%) for patients with central tumor, 73% (95%CI61–85%) and 44% (95%CI31–57%) for those with extremity tumor; 68% (95%CI 52–83%) and 46% (95%CI 32–54%) for OS, 64% (95%CI 42–85%) and 48% (95%CI 25–71%) for S, 48% (95%CI 13–82%) and 27% (95%CI 1–54%) for DCh. Conclusions: The protocol is feasible, but the chemotherapy-related toxicity is remarkable. Surgical complete remission is the main factor influencing survival. Central location and synchronous metastases are negative prognostic factors, but 50% 3-year OS can be achieved with aggressive local and systemic treatment. Osteosarcoma and high-grade sarcoma NOS benefit from chemotherapy more than patients with dedifferentiated chondrosarcoma. No significant financial relationships to disclose.

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Metabolic profile and neoadjuvant chemotherapy sensitivity in high-grade bone sarcoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e22506 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e22506-e22506

Author(s):

Pascaline Boudou-Rouquette ◽

Ithar Gataa ◽

Anne Jouinot ◽

Sixtine De Percin ◽

Audrey Bellesoeur ◽

...

Keyword(s):

Insulin Resistance ◽

Neoadjuvant Chemotherapy ◽

Preoperative Chemotherapy ◽

Metabolic Profile ◽

Tumor Necrosis ◽

Univariate Analysis ◽

Bone Sarcoma ◽

Model Assessment ◽

High Grade ◽

Bone Sarcomas

e22506 Background: Neoadjuvant chemotherapy with intercalated surgery is the standard of care for resectable high-grade bone sarcoma (BS) but identification of biomarkers for chemosensitivity prediction is still needed. Methods: We recruited 121 pts with new primary localized or metastatic BS, measured fasting blood glucose and insulin, body mass index (BMI). The HOMA-IR (Homeostasis Model Assessment) score ((Glucose (mmol/l) x Insulin) / 22.5), which has been proven to reliably detect insulin resistance was calculated, and patients with HOMA-IR > 2.6 were considered as insulin resistant (IR). We collected characteristics usually associated with insulin resistance (IR): age, obesity, diabetes, dyslipidemia and hypertension. Results: Out of 121 pts, 48 (40%) were IR: HOMA-IR > 2.6. Thirty IR patients (62%) had no cardiovascular risk factor. In univariate analysis, IR was associated with obesity (BMI > 30 kg/m2)(23% vs 3%, p = 0.0013), but not with age (median 38.4 vs 43.3 years, p = 0.15). IR was more prevalent in Ewing sarcoma (12/21; 57%) and chondrosarcoma (7/13; 54%) followed by osteosarcoma (25/61; 41%) and other rare bone sarcomas (4/26; 15.3%)(p = 0.037). After preoperative chemotherapy and surgery of Ewing tumor and osteosarcoma, pathologic tumor necrosis was higher in IR pts (85.8 vs 69.3%, p = 0.012). Using multivariate linear regression models, IR was independently associated with pathologic tumor necrosis (p = 0.042) but not with obesity (p = 0.55). Conclusions: Our results suggest that tumor-induced metabolic profile may help to discriminate best candidates for preoperative chemotherapy in high-grade bone sarcomas. Further studies are needed to confirm and explain these results.

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Multidisciplinary Management of a Rare Case of a Huge LowGrade Chondrosarcoma of the Lumbar Spine: A Case Report

Indonesian Journal of Cancer ◽

10.33371/ijoc.v14i4.740 ◽

2020 ◽

Vol 14 (4) ◽

pp. 139

Author(s):

Samuel Jason Rolando Tua ◽

Hendy Rachmat Primana ◽

Agus Hadian Rahim ◽

Ahmad Ramdan ◽

Herry Herman

Keyword(s):

Bone Sarcoma ◽

Tennis Ball ◽

High Grade ◽

Low Back ◽

X Rays ◽

Comorbid Conditions ◽

Primary Bone Sarcoma ◽

Primary Bone ◽

Viable Treatment

Introduction: Chondrosarcoma is the second most common primary bone sarcoma and arising in the spine. It is estimated to be 2% to 12% in incidence from various series. The use of neoadjuvant and adjuvant chemotherapy for chondrosarcomas is controversial. Low- and intermediate-grade chondrosarcomas respond poorly to chemotherapy. Although not much data on the efficacy of chemotherapy in the treatment of high-grade chondrosarcomas, it should be considered in any young patient with a high-grade tumor. Radiation is recommended when anything other than wide excision is performed for chondrosarcoma of any grade.Case Presentation: A 24-year old female presented to the clinic with a chief complaint of persistent low back pain and a lump in her back. Initially, the lump was the size of a tennis ball three years ago. At the time of the examination, the lump was at the size of a volleyball about 65 x 63 x 58 centimeters. Systemic and general examinations were unremarkable. There were no comorbid conditions. From the results of the Clinicopathological Conference conducted by neurologists, pathologists, radiologists, orthopedic spine and oncology surgeons, it is advisable to conduct investigations such as x-rays, CT scans, MRI, biopsy, and surgery is recommended for evaluation of expansion of chondrosarcoma, evolving the spinal cord, and for resection of tumors.Conclusion: Early diagnosis and complete resection of tumor and treatment of relevant symptoms represent a viable treatment for this rare disorder to achieve increased life expectancy, low recurrence of tumor, and improvement of quality of life.

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