The time to treatment interval (TTI), defined as the period from diagnosis to first definitive treatment, has very limited descriptions toward understanding delays in primary bone sarcoma (PBS) care. Our primary goal was to determine the national standard for time to treatment initiation (TTI) in PBS in adults and to identify characteristics associated with TTI variability.An analysis of the National Cancer Database identified 15,083 adult patients with PBS diagnosed from 2004 to 2013. Kruskal-Wallis analysis identified differences between covariates regarding TTI and regression modeling identified covariates that independently influenced TTI.The median TTI was 22 days. Approximately 60% of patients were definitively treated in the same center where the index diagnosis was made. Increased TTI was correlated with a transition in care institution (incidence rate ratio (IRR) = 1.89; P < 0.001), being uninsured (IRR = 1.36; P < 0.001), primary tumor site in the pelvis (IRR = 1.26; P < 0.001), Medicaid insurance status (IRR = 1.22; P < 0.001), care at an academic center (IRR = 1.14; P < 0.001), non-white race (IRR = 1.12; P=0.002), and Medicare insurance status (IRR = 1.08; P=0.017). Decreased TTI was correlated with a diagnosis of chondrosarcoma (IRR = 0.85; P < 0.001), having surgery as the index treatment (IRR = 0.88; P < 0.001), a primary tumor site of the lower (IRR = 0.91; P=0.001) or upper extremity (IRR = 0.92; P=0.023), and stage II or stage III disease (IRR = 0.91; P=0.010).TTI is associated with tumor, treatment, and socioeconomic and healthcare system characteristics. Transitions in care between institutions are responsible for the greatest increase in TTI. As TTI is more commonly used as a quality metric, physicians need to be aware of the causes for prolonged TTI, as we work to improve national delays in diagnosis and treatment initiation.
Abstract Ewing sarcoma (ES) is a malignant tumor of bone and soft tissue that most often occurs in adolescents and young adults. Despite an international coordinated approach, several nuances, discrepancies, and debates remain in defining the standard of care for treating ES. In this review, the authors leverage the expertise assembled by formation of the National Ewing Sarcoma Tumor Board, a multi‐institution, multidisciplinary virtual tumor board that meets monthly to discuss complicated and challenging cases of ES. This report is focused on select topics that apply to the management of patients with newly diagnosed ES. The specific topics covered include indications for bone marrow aspirate and biopsy for initial evaluation compared with fluorodeoxyglucose‐positron emission tomography, the role of interval compressed chemotherapy in patients aged 18 years and older, the role of adding ifosfamide/etoposide to vincristine/doxorubicin/cyclophosphamide for patients with metastatic disease, the data on and role of high‐dose chemotherapy with autologous stem cell transplantation, maintenance therapy, and whole‐lung irradiation. The data referenced are often limited to subgroup analyses and/or compiled from multiple sources. Although not intended to replace the clinical judgement of treating physicians, the guidelines are intended to provide clarity and recommendations for the upfront management of patients with ES. Plain Language Summary Ewing sarcoma is a malignant tumor of bone and soft tissue that most often occurs in adolescents and young adults. For this review, the authors used the experience of the National Ewing Sarcoma Tumor Board, a multi‐institution, multidisciplinary virtual tumor board that meets monthly to discuss complicated and challenging cases of Ewing sarcoma. Although not intended to replace the clinical judgement of treating physicians, the guidelines will focus on the development of consensus statements for the upfront management of patients with Ewing sarcoma.
Bone-seeking radiopharmaceuticals can deposit radiation selectively to some osteosarcoma tumours because of the bone-forming nature of this cancer.This is the first report of using 223-radium, an alpha-emitting calcium analogue with a high therapeutic index, in combination therapy with other agents in 15 patients with metastatic osteoblastic osteosarcoma.Candidates for alpha-radiotherapy if 99mTc-MDP bone scan had avid bone-forming lesions and no therapy of higher priority (eg, definitive surgery). Monthly 223-radium infusions (1.49 μCi/kg or 55.13 kBq/kg) were given.The median infusion number was three and the average time to progression was 4.3 months for this cohort receiving 223-radium+other agents. Agents provided during 223-radium included (1) drugs to reduce skeletal complications: monthly denosumab (n=13) or zolendronate (n=1); (2) agents with antivascular endothelial growth factor activity, pazopanib (n=8) or sorafenib (n=1), (3) alkylating agents: oral cyclophosphamide (n=1) or ifosfamide, given as a 14-day continuous infusion (n=1, two cycles), (4) high-dose methotrexate (n=1), pegylated liposomal doxorubicin (n=1); and (5) two other combinations: nivolumab and everolimus (n=1) and rapamycin and auranofin (n=1). Radiation therapy, including stereotactic body radiotherapy (SBRT), was also given to 11 patients concurrently with 223-radium (n=2), after 223-radium completion (n=3), or both concurrently and then sequentially for other sites (n=6). After 223-radium infusions, patients without RT had a median overall survival of 4.3 months compared with those with SBRT and/or RT, who had a median overall survival of 13.5 months.Conclusion Although only 1/15 of patients with osteoblastic osteosarcoma still remain alive after 223-radium, overall survival.
Abstract Ewing sarcoma (ES) is a malignant tumor of bone and soft tissue that most often occurs in children, adolescents, and young adults. Debate and controversy remain in the management of relapsed/refractory ES (RR‐ES). The authors leveraged the expertise assembled by the National Ewing Sarcoma Tumor Board, a multidisciplinary virtual tumor board that meets monthly to discuss challenging cases of ES. In this review, they focus on select topics that apply to the management of patients with RR‐ES. The specific topics covered include the initial approach of such patients and discussion of the goals of care, the role of molecular testing, chemotherapy regimens and novel agents to consider, the role of maintenance therapy, and the use of high‐dose chemotherapy with autologous stem cell rescue. The data referenced are often limited to subgroup analyses and/or compiled from multiple sources. Although not intended to replace the clinical judgement of treating physicians, these guidelines are intended to support clinicians and provide some clarity and recommendations for the management of patients with RR‐ES. Plain Language Summary Ewing sarcoma (ES) is a bone and soft tissue cancer that most often occurs in teenagers and young adults. This article uses the experience of the National Ewing Sarcoma Tumor Board, a multi‐institution, multidisciplinary virtual tumor board that meets monthly to discuss challenging cases of ES and to address questions related to the treatment of patients with relapsed ES. Although not intended to replace the clinical judgement of treating physicians and limited by available data, these consensus recommendations will support clinicians who treat patients with this challenging malignancy, made even more difficult when it recurs.
Myeloablative conditioning and AlloSCT in children with AML in CR1 is associated with a 60% event-free survival (EFS) but may be associated with significant acute toxicity and late effects (Woods et al; Blood, 2001). Reduced-intensity conditioning (RIC) and AlloSCT in children is safe, feasible and may be associated with less adverse effects (Del Toro/Cairo et al, BMT, 2004; Satwani/Cairo, BBMT, 2013). Gemtuzumab ozogamicin (GO) has been demonstrated to induce response in 30% CD33+ pediatric relapsed/refractory AML (Sievers et al, JCO, 2001). The dose of GO is significantly lower when combined with chemotherapy (Aplenc, JCO, 2008). We examined the feasibility and toxicity of RIC-AlloSCT followed by GO targeted immunotherapy in children with CD33+ AML in CR1/CR2. Conditioning consisted of fludarabine 30mg/m2 x 6 days and busulfan 3.2-4mg/kg x 2 days ± rabbit ATG 2mg/kg x 4 days followed by AlloSCT from matched related/unrelated donors. GO was administered ≥55 days post-AlloSCT in 2 doses (8 weeks apart), following a dose escalation design (4.5, 6, 7.5 and 9 mg/m2). Thirteen patients with average risk AML received RIC AlloSCT: median age of 14.5 years at transplant (range: 11-21); M:F:7:6; disease status at AlloSCT: 10 CR1, 3 CR2. Eleven patients received AlloSCT from 5-6/6 HLA matched family donors: 8 received PBSCs, 2 received BM and 1 received umbilical cord blood transplantation (UCBT). Two patients received an unrelated graft (HLA matching 1 4/6 and 1 9/10) from UCBT and BM, respectively. Neutrophil engraftment and platelet engraftment was observed in 13 patients (100%) and was achieved at a median of 14 days (range 7-31) and 18 days (range 10-52), respectively. Three patients received GO at dose level 1 (4.5 mg/m2/dose), 5 at dose level 2 (6 mg/m2/dose), 3 at dose level 3 (7.5 mg/m2/dose) and 2 at dose level 4 (9 mg/m2/dose). The first dose of GO was administered after 55 days post-transplant. One patient experienced grade III transaminitis which resolved; no grade IV transaminitis, no grade III/IV hyperbilirubinemia or VOD. Twelve and 7 patients experienced grade 4 myeloid toxicity and grade 4 thrombocytopenia, respectively. Following the first dose of GO, neutrophil and platelet recovery was achieved at median of 14 days (range 9-18) and 11 days (range 6-17), respectively. The second dose of GO was given at a median of 143 days (range: 120-209) post-transplant. The probability of grade II-IV aGVHD was 15.4%. Probability of overall survival following RIC-AlloSCT and GO consolidation at 1 and 3 years was 83.3% and 65.6%, respectively. There have been no DLTs observed in this cohort during this time period. This preliminary data demonstrates that RIC followed by AlloSCT and consolidation with GO appears to be safe in children with CD33+ AML in CR1/CR2. A larger cohort with longer follow-up is required to determine the long-term clinical significance.
Background: Stereotactic body radiation therapy (SBRT) is increasingly used for patients with recurrent and or metastatic tumors. Sarcomas are generally considered not sensitive to radiotherapy and SBRT may allow for increased biological effectiveness. We report intermediate outcomes and toxicity for pediatric, adolescent, and young adult patients treated with SBRT to sites of recurrent and or metastatic sarcoma Procedure: We queried an Institutional Review Board-approved registry of patients treated with SBRT for metastases from pediatric sarcomas. Patients age 29 and below were assessed for local control, survival, and toxicity. Results: Thirty-one patients with a total of 88 lesions met eligibility criteria. Median patient age was 17.9 years at treatment. Sixteen patients were treated with SBRT to >1 site of disease. The median dose was 30 Gy in 5 fractions. The median follow-up time was 7.4 months (range: 0.2 to 31.4 mo). Patients were heavily pretreated with systemic therapy. In 57 lesions with >3 months of radiographic follow-up, the 6-month and 12-month local control rates were 88.3%±4.5% and 83.4%±5.5%, respectively. Radiographic local failures were rare (6/57 in-field, 4/57 marginal). Only 1/88 treated lesions was associated with a radiation-related high-grade toxicity; late grade 3 intestinal obstruction in a re-irradiated field while on concurrent therapy (gemcitabine and docetaxel). No acute grade ≥3 toxicity was observed. Conclusions: SBRT was well tolerated in the majority of patients with favorable local control outcomes. Additional studies will be required to determine the optimal SBRT dose and fractionation, treatment volume, and appropriate concurrent therapies.
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