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Background: Heterozygous isocitrate dehydrogenase (IDH) mutations occur in about half of conventional central bone chondrosarcomas (CCBC). Aim of this study was to assess the frequency and prognostic impact of IDH mutations in high grade CCBC patients. Methods: 64 patients with G2 and G3 CCBC were included. DNA extraction, PCR amplification of IDH1/2 exon 4s, and sequencing analysis with Sanger were performed. Results: IDH mutations were detected in 24/54 patients (44%): IDH1 in 18, IDH2 in 4, and both IDH1/2 in 2 patients. The frequency of mutations was 37% in G2 vs. 69% in G3 (p = 0.039), and 100% in three Ollier disease associated chondrosarcoma. 5-year overall survival (OS) at 124 months (range 1-166) was 51%, with no significant difference based on the IDHmutational status: 61% in IDHmut vs 44% in IDH wild type (IDHwt). The 5-year relapse free survival (RFS) was 33% (95% CI:10-57) for IDHmut vs 57% (95%CI: 30-77) for IDHwt. Progression free survival (PFS) was 25% (95%CI:1-65) IDHmut vs. 16% (95%CI: 0.7-52) IDHwt. 55% (5/9) of IDHmut G2 became higher grade at the recurrence, as compared with 25% (3/12) of G2 IDHwt. Conclusions: This study shows a higher frequency of IDH mutations in G3 CCBC as compared with G2. No significant differences in OS, RFS, and PFS by mutational status were detected. After relapse, a higher rate of G3 for IDH mutated CCBC was observed.

Rationale and objectives Myxofibrosarcoma (MFS) is a common soft tissue sarcoma in the elderly patients with both clinical and magnetic resonance imaging (MRI) peculiar features: very high recurrence rate, relatively low risk of distant metastases. On MRI it shows an infiltrative pattern (“tail sign”) and high myxoid matrix content with water-like appearance on fluid-sensitive sequences. Due to these unusual characteristics, we propose a specific MRI grading system to stratify the risk of local recurrence (LR) and offer other prognostic information. Materials and methods: Two expert radiologists retrospectively and blindly reviewed preoperative MRI of 150 patients affected by MFS of the extremities treated at a single Institution. Myxoid matrix component and contrast enhancement of the tumor were evaluated and graded with a semiquantitative method. The presence of an infiltrative pattern, the depth of the tumor (deep and/or superficial) and tumor sizes were also recorded. MRI features were analyzed separately and correlated to LR risk, sarcoma specific survival and distant metastases rate. Then, according to the statistical significance of the correlation between MRI features and prognosis a 3-grade scoring system was proposed and evaluated to assess the risk of LR. Results: Mean age was 66.1 ± 14.4 years; mean follow-up was 16 ± 28.3 months. The MRI features most associated with higher risk of LR resulted to be: lesion sizes (both volume and maximum diameter with a cut-off of 20 cm – p = 0.01), the “tail sign” (p = 0.045), and high myxoid matrix content with MRI water-like appearance (p = 0.0493). Ninety-four patients (94 of 150- 62.7%) were grade 1, 33 (22.0%) grade 2, and 23 (15.3%) grade 3. Interobserver agreement was substantial with K= 0.779 (95%CI 0.685–0.874). Higher grades of MRI grading system proposed were significantly associated with an increased LR risk, hazard ratio = 2.031 (95%CI 1.366–3.019; p Conclusion: This is the largest series evaluating MRI features as prognostic factors for MFS. The MRI grading system proposed is significantly able to stratify the risk of LR in MFS of the extremities. The system is applicable to all the standard MRI studies protocols, might help in surgical planning, and may offer prognostic information.

Aim To evaluate the activity and safety of the PD-1 antibody pembrolizumab in adult patients with advanced osteosarcoma. Material and methods The study was a single-arm, open-label, phase 2 trial in patients with unresectable, relapsed osteosarcoma. The primary endpoint was clinical benefit rate (CBR) at 18 weeks of treatment, defined as complete response, partial response, or stable disease using RECIST v1.1. The trial had a Simon´s two-stage design, and ≥ 3 of 12 patients with clinical benefit in stage 1 were required to proceed to stage 2. The trial is registered with ClinicalTrials.gov, number NCT03013127. NanoString analysis was performed to explore tumor gene expression signatures and pathways. Results Twelve patients were enrolled and received study treatment. No patients had clinical benefit at 18 weeks of treatment, and patient enrollment was stopped after completion of stage 1. Estimated median progression-free survival was 1.7 months (95% CI 1.2–2.2). At time of data cut-off, 11 patients were deceased due to osteosarcoma. Median overall survival was 6.6 months (95% CI 3.8–9.3). No treatment-related deaths or drug-related grade 3 or 4 adverse events were observed. PD-L1 expression was positive in one of 11 evaluable tumor samples, and the positive sample was from a patient with a mixed treatment response. Conclusion In this phase 2 study in advanced osteosarcoma, pembrolizumab was well-tolerated but did not show clinically significant antitumor activity. Future trials with immunomodulatory agents in osteosarcoma should explore combination strategies in patients selected based on molecular profiles associated with response.

Background: Giant cell tumors of bone (GCTB) are osteolytic tumors. Denosumab, a RANK-L inhibitor, is approved for GCTB. Data on serum bone turnover marker (sBTM) changes are lacking. We present a phase II correlative study on sBTMs in GCTB patients treated with denosumab. Methods: All GCTB patients receiving denosumab within a multicentre, open-label, phase 2 study were enrolled. Serum levels of carboxyterminal-crosslinked-telopeptide of type I collagen (s-CTX), alkaline phosphatase (ALP), bone-alkaline phosphatase (bALP), parathyroid hormone (sPTH), and osteocalcin (OCN) were prospectively assessed (baseline, T0, 3 months, T1, 6 months, T2). The primary endpoint was assessment of sBTM changes after denosumab; the secondary endpoints were disease-free survival (DFS) and sBTM correlation. Results: In 54 cases, sBTMs decreased during denosumab treatment except for sPTH. With a median follow-up of 59 months, 3-year DFS was 65% (%CI 52–79), with a significantly worse outcome for patients with high (≥500 UI/mL) s-CTX at baseline, as compared to low s-CTX (

Background: According to retrospective osteosarcoma series, ABCB1/P-glycoprotein (Pgp) overexpression predicts for poor outcomes. A prospective trial to assess a risk-adapted treatment strategy using mifamurtide in Pgp+ patients was performed. Methods: This was a phase 2, multicenter, uncontrolled trial including patients 40 years old or younger with nonmetastatic extremity high-grade osteosarcoma stratified according to Pgp expression. All patients received high-dose methotrexate, doxorubicin, and cisplatin (MAP) preoperatively. In Pgp+ patients, mifamurtide was added postoperatively and combined with MAP for a good histologic response (necrosis ≥ 90%; good responders [GRs]) or with high-dose ifosfamide (HDIFO) at 3 g/m2/d on days 1 to 5 for a histologic response < 90% (poor responders [PRs]). Pgp– patients received MAP postoperatively. After an amendment, the cumulative dose of methotrexate was increased from 60 to 120 g/m2 (from 5 to 10 courses). The primary end point was event-free survival (EFS). A postamendment analysis was performed. Results: In all, 279 patients were recruited, and 194 were included in the postamendment analysis: 70 (36%) were Pgp–, and 124 (64%) were Pgp+. The median follow-up was 51 months. For Pgp+ patients, 5-year EFS after definitive surgery (null hypothesis, 40%) was 69.8% (90% confidence interval [CI], 62.2%-76.2%): 59.8% in PRs and 83.7% in GRs. For Pgp– patients, the 5-year EFS rate was 66.4% (90% CI, 55.6%-75.1%). Conclusions: This study showed that adjuvant mifamurtide, combined with HDIFO for a poor response to induction chemotherapy, could improve EFS in Pgp+ patients. Overall, the outcomes compared favorably with previous series. Mifamurtide and HDIFO as salvage chemotherapy are worth further study.

11559 Background: Over the last decade, the category of undifferentiated round cell sarcomas (URCS), defined by the absence of Ewing sarcoma-associated translocations, has emerged. Aim of this study was to assess prevalence of each entity and outcome after genomic classification. Methods: Ewing sarcoma and other URCS diagnosed between 1920 and 2020 were reviewed. All URCS with available material were analyzed with FISH, RT-qPCR and/or Archer FusionPlex Sarcoma Panel. Demographic and treatment were collected. Survival was analyzed in patients with available follow-up. Results: 1995 cases identified, 20 cases lacked material for further genetic analysis and were excluded. 1975 cases were classified as follows: 1925 Ewing sarcomas (97.47%), 25 CIC-rearranged sarcomas (1.27%), 16 BCOR-CCNB3 rearranged sarcomas (0.81%), 2 EWSR1-NFATC2 sarcoma (0.1%), one each as CIC-LEUTX and FUS-NFATC2 rearranged sarcoma (0.05% each), and 5 as unclassified URCS (0.25%). A different presentation according to tumor type was shown in 43/50 ultra-rare tumors (Table). Forty-one/50 cases had available follow-up: 20/41 patients underwent surgery, 14/41 surgery+radiotherapy, 6 radiotherapy only, and no local treatment for 1 patient. Chemotherapy was administrated to 36/41 patients (Ewing sarcoma drugs in 16/22 CIC-DUX-4 and 8/11 BCOR-CCNB3; osteosarcoma drugs in 2/11 BCOR-CCNB3, and doxorubicin/ifosfamide in 2/22 CIC-DUX4 and 2/5 URCS; not specified in 6 cases). The 3-years overall survival (OS) was 32.7%f for CIC-rearranged sarcomas (75% in localize disease, 7,7% for the advanced disease, p 0.0084), 81.8% for BCOR-CCNB3 sarcomas (87.5% localized, 66.7% advanced; p 0.0734), and 60% for URCS (p 0.057). 1 patient with CIC-LEUTX sarcoma presenting with metastases died 13 months from diagnosis, 1 patient with FUS-NFATC2 and 1 with EWSR1-NFATC2 rearrenged sarcomas were alive without disease at 8 and 5 years from onset. Conclusions: Prevalence of URCS characterized by a combination of morphologic observation ad molecular techniques is provided. The majority of the cases underwent surgery or surgery combined with radiotherapy, and Ewing-like chemotherapy. The survival difference among different entities underscores the need of accurate subclassification of round cell sarcomas. Novel drugs for CIC-DUX-4 sarcomas presenting with metastases are needed. [Table: see text]

Background Giant cell tumor of bone (GCTB) is a progressive osteolytic tumor with proven response to denosumab when unresectable or at high surgical risk. We report on incidence of suspected (sONJ) and adjucated (aONJ) osteonecrosis of the jaw cases, from a single institution series of patients treated with denosumab within a phase 2 study Methods Patients were enrolled with unresectable GCTB (Cohort 1), resectable GCTB with planned high morbidity surgery (Cohort 2). Denosumab was given 120 mg SC every 4 weeks with loading doses on days 8 and 15. The primary endpoint was safety: aONJ and s ONJ rate; efficacy endpoints included proportion of Cohort 2 patients without surgery, and progression-free survival for all patients Results Baseline characteristics and ONJ results for 52 patients are shown in the Table 1. Median follow-up was 103 months (95%CI 55-126) in Cohort 1 and 105 months (95%CI 94-116) in Cohort 2. Overall response rate was 20% in all sample. Of 9 Cohort 1 patients, 1 ended denosumab for GCTB progression after 70 months of follow-up. Overall Kaplan Meier (KM) estimates (95% CI) for GCTB progression-free in these patients were 88% (39-98%). 23 Cohort 2 pts (53%) ended denosumab without GCTB progression, and 20 (47%) recurred with a KM estimate of 67% (51-79) at 24 months, and 52% (36-66%) at 60 months. Median time of denosumab therapy was 80 months in Cohort 1 and 14 months in Cohort 2. Within Cohort 2 patients with planned surgery, 88% underwent surgery and 12% continued with denosumab only. Following surgery, recurrence occurs higher after curettage than resection (47% vs 5%). ONJ rate is reported in Table 1. Conclusions Denosumab was generally well tolerated with excellent long-term disease control in unresectable patients. A 47% recurrence rate following surgery was seen in this high-risk, selected, resectable population. Denosumab has major, long-lasting antitumor activity in unresectable or metastatic GCTB, with an aONJ and sONJ rate of 4% and 8%, respectively, in this series.

BackgroundThis study compared the clinical and functional outcomes of patients initially treated with observation or medical treatment with those of patients treated with local treatment (surgery alone or surgery with adjuvant radiotherapy) to confirm whether observation or medical treatment is an appropriate first-line management approach for patients with desmoid tumors.MethodsWe retrospectively reviewed the medical records of 99 patients with histologically confirmed primary desmoid tumors treated between 1978 and 2018. The median follow-up period was 57 months. We evaluated event-free survival, defined as the time interval from the date of initial diagnosis to the date of specific change in treatment strategy or recurrence or the last follow-up.ResultsAn event (specific change in treatment strategy or recurrence) occurred in 28 patients (28.3%). No significant difference in event-free survival was found between the first-line observation/medical treatment and local treatment groups (p= 0.509). The median Musculoskeletal Tumor Society score of the patients treated with first-line local treatment was 29 (interquartile range [IQR], 23–30), whereas that of the patients managed with first-line observation or medical treatment was 21 (IQR, 19–29.5). First-line observation or medical treatment was more frequently chosen for larger tumors (p= 0.045). In the patients treated with local treatment, local recurrence was not related to the surgical margin (p= 0.976).ConclusionUpfront surgery is not advantageous compared to more conservative treatments such as observation or medical treatment for patients with desmoid tumors.

Background: The evidence on high-dose ifosfamide (HD-IFO) use in patients with relapsed osteosarcoma is limited. We performed a retrospective study to analyze HD-IFO activity. Methods: Patients with osteosarcoma relapsed after standard treatment [methotrexate, doxorubicin, cisplatin +/&minus, ifosfamide (MAP+/&minus, I)] with measurable disease according to RECIST1.1 were eligible to ifosfamide (3 g/m2/day) continuous infusion (c.i.) days 1&ndash, 5 q21d. RECIST1.1 overall response rate (ORR) (complete response (CR) + partial response (PR)), progression-free survival at 6-month (6m-PFS), duration of response (DOR), and 2-year overall survival (2y-OS) were assessed. PARP1 expression and gene mutations were tested by immunohistochemistry and next-generation sequencing. Results: 51 patients were included. ORR was 20% (1 CR + 9 PR). Median DOR was 5 months (95%CI 2&ndash, 7). Median PFS, 6m-PFS, OS, and 2y-OS were 6 months (95%CI 4&ndash, 9), 51%, 15 months (10&ndash, 19), and 30%, respectively. A second surgical complete remission (CR2) was achieved in 26 (51%) patients. After multivariate analysis, previous use of ifosfamide (HR 2.007, p = 0.034) and CR2 (HR 0.126, p &lt, 0.001) showed a significant correlation with PFS and OS, respectively. No significant correlation was found between outcomes and PARP1 or gene mutations. Conclusions: HD-IFO should be considered as the standard first-line treatment option in relapsed osteosarcoma and control arm of future trial in this setting.

Chondroblastoma is a rare benign chondrogenic tumor that occurs in skeletally immature patients between ages 10 and 20 years old. In literature are reported few cases of lung metastases, mainly occurred after surgery or local recurrences. There is no evidence on the pathogenesis of lung metastasis, as well as pulmonary disease course. Few treatments for metastases with aggressive behavior were based on chemotherapy regimen employed in other sarcoma with no results or not satisfying ones. Denosumab is approved for treatment of giant cell tumors and it is under investigation for other giant cell-rich bone tumors. Here, we report a case of a 16-year-old male chondroblastoma of the left humerus with bilateral lung metastases at presentation and progressing during follow-up, treated with denosumab for almost 2 years. We confirm that denosumab treatment can be effective in controlling chondroblastoma metastasis and it has been a safe procedure in an adolescent patient.

Background. In relapsed osteosarcoma, the 5-yr postrelapse disease-free survival (PRDFS) rate after the second relapse is Viscum album fermentatum Pini (an extract derived from the parasitic plant Viscum album L., European mistletoe) as maintenance therapy in patients with metastatic osteosarcoma in complete surgical remission after the second relapse. The primary endpoint was the PRDFS rate at 12 months (compared to the historical control rate). This is a long-term updated result. Patients and Methods. 10 patients received oral etoposide 50 mg/m2 daily for 21 days every 28 days for 6 months, and 9 patients received Viscum album fermentatum Pini 3 times/wk subcutaneously for 1 year. The study closed early in July 2011 due to insufficient recruitment. Lymphocyte subpopulations were analyzed at T0, T3, T6, T9, and T12 months. Results. On 30 June 2019, at a median follow-up ITT of 83 months (range 3–144 ms), a median PRDFS of 106 ms (2–144) was observed in the Viscum arm with 5/9 patients who never relapse vs a PRDFS of 7 months (3–134) in the etoposide arm (all patients in the Etoposide arm relapsed) (hazard ratio HR = 0.287, 95% CI: 0.076–0.884, p=0.03). Model forecast 10-yr overall survival rates as 64% in the Viscum arm and 33% in the etoposide arm. Lymphocyte subpopulation counts (CD3, CD4, and CD56) showed an increase in the Viscum arm while a decrease was observed in the etoposide arm during treatment. Conclusions. After 12 years from the start of the trial, the patients in the Viscum arm continue to show a considerably longer PRDFS compared to oral etoposide, and a trend for an advantage in OS is evident even if the number of treated patients is too small to draw conclusions. Viscum as maintenance treatment after complete surgical remission in relapsed osteosarcoma should be further investigated and compared with other drugs.

Systemic treatments for advanced soft tissue sarcoma are limited. Eribulin showed activity in metastatic soft tissue sarcoma, particularly liposarcomas. Data from six patients with advanced liposarcoma that received eribulin as third- or fourth-line therapy are presented herein. Eribulin treatment was well tolerated; no grade 3–4 toxicity or therapy delay was observed. Two patients had a partial response; four had a prolonged stable disease. The first case, with pre-existing chronic renal dysfunction, achieved a 6-month stable disease with dose-reduced eribulin. The second case became resectable after eribulin treatment, with a 6-month complete surgical remission. The third case obtained a 7-month stable disease with eribulin and stereotactic body radiotherapy. The last three cases were ≥65 years old, and two of them had objective response with eribulin.

Osteosarcoma is a rare bone tumor that occurs in young adults with a subsequent peak in the fifth decade. Neoadjuvant and adjuvant chemotherapy and surgery cure approximately 60% of patients with l...

This mono-institutional observational study was conducted to determine incidence, severity, risk factors, and outcome of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) in high-risk Ewing sarcoma (ES) patients treated with intravenous busulfan and melphalan (BU-MEL) followed by autologous stem cell transplantation (ASCT). During the past 10 years, 75 consecutive ES patients resulted evaluable for the analysis. After diagnosis of SOS/VOD, defibrotide therapy was started as soon as the medication was available. The variables analyzed as potential risk factors were: gender, patient's age at diagnosis, primary tumor site, disease stage, and prior radiation therapy (RT) given, focusing on RT liver exposure. The median age at diagnosis was 18.8 years. Five patients developed moderate to severe SOS/VOD (cumulative incidence, 6.67%). None of 32 pediatric patients (≤17 years) developed SOS/VOD (p = 0.0674). In univariate analysis, prior RT liver exposure resulted statistically significant (p = 0.0496). There was one death due to severe SOS/VOD. This study reports the largest series of high-risk ES patients treated with intravenous BU-MEL before ASCT. The incidence of SOS/VOD was lower when compared with other studies that used oral busulfan. Any prior RT liver exposure should be avoided. Earlier defibrotide treatment confirms to be effective.

e22507 Background: We compared toxicity and outcomes of BuMel and TreoMel HDCT consolidation with stem cell rescue in high-risk ES pts prospectively treated in 5 consecutive trials at the Istituto Ortopedico Rizzoli, Bologna, Italy. Methods: Eligible pts had histologically proven diagnosis of ES, high-risk disease defined as localized disease with poor histological/radiological response to standard chemotherapy or lung/pleural metastases or extra-pulmonary metastases or relapsed disease, were aged < 40. All pts received previous standard chemotherapy (vincristine, ifosfamide, doxorubicin, etoposide, cyclophosphamide actinomycin-D) and surgery and/or radiation therapy (RT) as local treatment. From June 1, 2011, TreoMel was used instead of BuMel to avoid potential severe complications related to busulfan, as in case of previous RT on axial skeleton/pelvis. Pts with lung metastases received lung irradiation 12-15 Gy at least 2 months after HDCT. Results: Between January 1, 2007, and September 30, 2018, 98 pts received BuMel or TreoMel: 52 pts with localized disease (7 TreoMel), 26 pts with lung/pleural metastases (5 TreoMel), 10 pts with extra-pulmonary metastases (4 TreoMel) and 10 pts with relapsed disease (1 TreoMel). Median age was 18 yrs (range 3-39 yrs). 14 out of 17 TreoMel pts received previous RT on axial skeleton/pelvis. Median follow up is 4.2 yrs (range 10 mo. - 12 yrs). Pts treated with TreoMel showed a significant lower incidence of grade 3-4 stomatitis (p = < 0.001) and of all grade ≥ 3 non-hematological toxicities (p = < 0.001). One pt died of BuMel-related toxicity (sinusoidal obstruction syndrome/veno-occlusive disease) and none after TreoMel. For localized ES, the 5yr-EFS was 66.7% (95%CI, 47.9-78) for BuMel pts and 66.7% (95CI%, 19.5-90.4) for TreoMel pts. Conclusions: In high-risk ES, TreoMel is significantly less toxic then BuMel. Combining RT on central/axial sites and TreoMel is feasible. In localized ES, results show similar 5yr-EFS between BuMel and TreoMel. TreoMel could be used instead of BuMel when busulfan is contraindicated.

Background: High-grade bone osteosarcoma has a high relapse rate. The best treatment of local recurrence (LR) is under discussion. The aim of this study is to analyze LR patterns and factors prognostic for survival. Methods: LR diagnostic modality (clinical or imaging), pattern of recurrence, and post-LR survival (PLRS) were assessed. Results: Sixty-two patients were identified, with median age 21 years (range, 9–75 years), including 11 (18%) ≤15 years, 30 (48%) from 16 to 29 years; 21 (34%) were older. Patterns of relapse were LR only 58%, LR + distant metastases (DM) 42%. Seventy-nine percent of patients relapsed within 24 months, and diagnosis was clinical in 88%. LR treatment was surgery 85%, chemotherapy 55%, chemotherapy + surgery 45%. Surgical complete remission after LR (CR2) was achieved in 60% (LR 86%; LR + DM 23%). With a median follow-up of 43 months (range, 5–235 months), the five-year PLRS was 37%, significantly better for patients with longer LR-free interval (LRFI; ≤24 months 31% vs>24 months 61.5%, P=0.03), absence of DM (no DM 56%vs DM 11.5%, P=0.0001), and achievement of CR2 (no CR2 0%vs CR2 58.5%, P=0.0001). No difference was found according to age and chemotherapy (LR only: five-year PLRS: 53% without chemotherapy vs 58% with chemotherapy, P=0.9; LR + DM: five-year PLRS: 25% without chemotherapy vs 9% with chemotherapy, P=0.7). Conclusions: Early relapse is detected by symptoms in 90% of cases and associated with worse outcome. The achievement of CR2, not age, is crucial for survival. For patients with LR only, better survival was demonstrated, as compared with DM, and no improvement with chemotherapy after surgery was found.

Background Ewing sarcoma (ES) is the second most common bone tumor in adolescents and children. Staging workup for ES includes imaging and bone marrow biopsy (BMB). The effective role of BMB is now under discussion. Procedure A monoinstitutional retrospective analysis reviewed clinical charts, imaging, and histology of patients with diagnosis of ES treated at the Rizzoli Institute between 1998 and 2017. Results The cohort included 504 cases of ES of bone; 137 (27%) had metastases at diagnosis, while the remaining 367 had localized disease. Twelve patients had a positive BMB (2.4%). Eleven had distant metastases detected at initial workup staging with imaging assessment: six patients presented with bone metastases, five with both bone and lung metastases. Only one patient with ES of the foot (second metatarsus) was found to have bone marrow involvement with negative imaging evaluation (0.3%). Conclusions On the basis of our data, we suggest reconsidering the effective role of BMB in initial staging workup for patients with ES with no signs of metastases by modern imaging techniques. In metastatic disease, the assessment of the bone marrow status may remain useful to identify a group of patients at very high risk who could benefit from different treatment strategies.

e23506 Background: Metastatic osteosarcoma (MOS) with synchronous metastases accounts for 20-25% of all new cases of osteosarcoma. Lungs are the most common site of metastases at presentation (80%) followed by Bone (10%). 5- years Overall Survival (OS) of MOS ranges from 11 to 40%. In a previous study from our institution (Bacci G 2006) on 57 pts < 40 years old (1995-2000) the 2- and 5-year OS were 55% and 18%. Methods: Data of patients with pathologic and radiologic confirmed MOS with adequate follow up were reviewed (EC Approval N 916/2020/Oss/IOR). Time-to-event outcomes were estimate with Kaplan-Meier method and compared between groups with log-rank test and Cox model. Results: From August 2000 to October 2018, 92 patients had a diagnosis of MOS: median age 16.5 yrs (6-73, twelve pts > 40 ), gender rate was M 51/F 41, axial primary tumor in 15 cases, extremity in 77. Lung only metastases were described in 66 (71.7%). In 75/90 cases primary tumor was surgically removed, 43 (46%) cases had at least one surgical metastasectomy. All patients received chemotherapy: preoperative only in 6 cases, postoperative in 6, and pre and postoperative in 66 patients. The 1st line chemotherapy was a combination of drugs: Adriamycin in 91/92 pts, Cisplatin in 89/92, Ifosfamide in 88/92, Methotrexate in 83/92; 59 patients received a 2nd line chemotherapy, 34 pts received a 3rd line; most employed regimen were Gemcitabine-Docetaxel, Ifosfamide 15 gr/m2, Cyclophosphamyde-Etoposide, TKI (Pazopanib, Sorafenib), and a few received experimental drugs. Complete remission (CR) was obtained in 26/92 (28%), in 19 cases after surgical metastasectomy.In 30 pts the information of PGP (P- glycoprotein) was available; patients with positive PGP (19/30) had a worst overall survival as compared to those PGP negative (P = 0.038). Of those in Complete Remission 14/26 relapsed. At December 2020 with a median follow-up of 95 ms (IQR 34-159): 65/92 (70%) died , 12 are alive and free from disease , 6 are alive with disease, 9 were lost . The 2-yrs OS for all 92 pts from diagnosis was 66% (95%CI 55-75) and 5-yrs OS was 26% (95% CI 16-37). From the end of treatment, for those who reached a CR the 5-year OS was 57% vs 9% for those who did not (P < 0.001). At univariate analysis, primary tumor site (2-y OS 48% axial vs 72% extremity, P < 0.001), site of metastases (2-y OS 74% only lung vs 48% other, P = 0.004) and number of lung nodules (P = 0.007), were significantly associated to OS. At multivariate analysis, only site of metastases (other vs. only lung HR = 2.26, 95%CI: 1.21-4.22) and number of lung nodules (≥10 nodules vs ≤3 HR = 2.44, 95%CI: 1.24-4.81) were confirmed as significant for OS. Conclusions: Compared to our previous report from 20 yrs ago, 2-years and 5 yrs OS of MOS has improved but it remain unsatisfactory (66% vs 55% and 26% vs 18%).

e22010 Background: Osteosarcoma is a malignant primitive bone tumor whose prognosis is not changed since 4 decades, after the introduction of neoadjuvant chemotherapy with Methotrexate, Cisplatin, Doxorubicine and Ifosfamide. Histologic response to preoperative chemotherapy is a significant prognostic factor. Huvos I (necrosis ≤ 50%) has worst prognosis . Previous studies reported a 3 years EFS of this Huvos I patients around 25% (Tsuda Y,2020). In order to evaluate if survival has changed in recent years in this unfavourable prognostic group we evaluated the outcome of osteosarcoma patients with Huvos I. Methods: from our Pathology archieves we retrieved all cases of localized osteosarcoma treated at Rizzoli with neoadjuvant chemotherapy who reported an histologic necrosis below or equal to 50% (Huvos I grade) after preoperative chemotherapy MAP (Ethical C. Approval 917/2020/Oss/IOR). Results: from 2003 to 2019 we had 70 cases of localized osteosarcoma with Huvos I necrosis after neoadjuvant chemotherapy ( MAP in 66 and MAPI in 4) evaluable. Median age 21,5 (3-70); M:F = 44:26. 10/70 had axial localization vs extremity(60), subhistotype distribution:46 osteoblastic,11 chondroblastic, 7 fibroblastic, 5 teleangectatic, one not classified. In 24 cases PgP was available(14 PgP positive). With a median follow up of 86.7 ms (IQR 41-136) 43/70 had already relapsed. The median EFS was 25 ms (95% CI 15-42) and the 3 yrs EFS was 40.6% (95% CI 29-52). The 3 yrs overall survival was 80% (95%CI 68-88) and median OS was not reached. Axial tumor site was associated with significant inferior EFS (P = .004). Conclusions: these data confirm the poor prognosis of patients with necrosis ≤50% and the need of new drugs to improve their survival in this sub-group.

Purpose: 5-years overall survival (OS) in high grade conventional chondrosarcoma is about 50%. Grade has been identified as the main prognostic factor. Heterozigous isocitrate dehydrogenase (IDH) mutations are present in about half of conventional chondrosarcomas, with higher frequency in low grade lesions. IDH prognostic role is not fully understood. Aim of this study is to assess the frequency of IDH mutations in high grade chondrosarcoma, their relationship with clinical characteristics, and their prognostic role. Methods: patients who underwent surgery at Rizzoli between 2002 and 2012 with a diagnosis of G2- G3 conventional chondrosarcoma and fresh frozen tissue available were selected from archives. DNA extraction was performed with commercial kit. PCR amplification of exon 4 of IDH1 and IDH2 genes, and sequencing analysis with Sanger was performed. Results: 54 patients identified:18 (33%) were male, 36 (67%) female; median age was 62 (range 17-85 years). 40 (74%) patients had localized tumor, and 14 (26%) presented with metastases. Tumor was in the extremities in 25 (46%) patients. 41 (76%) of the cases were G2, 13 (24%) G3. 4 patients had a genetic predisposition (1 Maffucci syndrome and 3 Ollier disease). IDH mutation was detected in 26 (48%) of the patients (20 IDH1, 4 IDH2, and 2 patients both IDH1 and 2). Frequency of mutation was 17 (65%) in G2, and 9 (35%) in G3. 4/4 chondrosarcomas in with a syndrome presented a mutation. Gender, site and stage were not significantly different by mutational status. After a median follow-up of 124 months (range 1-166) the 5-year OS was 51% (95% CI:36-64), with no difference according to mutational status (5-year OS IDHmut 54% vs IDHwt 48%, p=0.45), and better survival for localized vs metastatic pts (68% vs 7%, p Citation Format: Elisabetta Setola, Stefania Benini, Alberto Righi, Gabriella Gamberi, Sofia Avnet, Elisa Carretta, Cristina Ferrari, Emanuela Palmerini, Pier Luigi Lollini, Marilena Cesari, Anna Paioli, Alessandra Longhi, Davide Maria Donati, Nicola Baldini. IDH mutations in G2-3 conventional chondrosarcoma of bone: a mono institutional experience [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5909.

e23564 Background: Activity of temozolomide (TEM) and irinotecan (IRI) in recurrent Ewing sarcoma (EWS) was demonstrated. Few data are available on TEMIRI use upfront. Biological predictive factors are lacking. Methods: This multi-institutional retrospective study (NCT03542097) included 59 patients with EWS. 8 patients with very high risk (HR) EWS (multivisceral ± bone marrow) received TEMIRI (TEM 100 mg/m2/day oral, and IRI 40 mg/m2/day intravenous, days 1-5, every 21 days) upfront, 51 patients after relapse (28% in 1st line, 72% ≥ 2nd line). Overall response rate (ORR: CR+PR), SD, and PD, progression-free (PFS) and overall survival (OS) were assessed. The relationship between pre-treatment expression of MGMT and ABCG2 (when FFPE tissue available) with ORR, PFS and OS was evaluated. Results: Median age was 27 years (range 4-62 years): 47 patients (80%) were adults (≥18 years), 35 (61%) had ECOG 0 and 42 (71%) presented with multivisceral disease (+ bone marrow in 5). MGMT was positive in 16/30 (53%), ABCG2 in 4/33 (12%). ORR for upfront TEMIRI (n = 8) was 50% (CR + PR = 1 + 3), with SD 50%, while in recurrent EWS (n = 49, 2 patients no measurable by RECIST) ORR was 31% (CR + PR = 4 + 11), SD 38%, and PD 31%. A better ORR was observed in adult (p = 0.008) & ECOG 0 (p = 0.001) patients; MGMT & ABCG2 expression did not influence ORR. 6-mos PFS was 87% after TEMIRI upfront, 43% at recurrence (p = 0.06), and 65% vs 28% (p = 0.02) for ECOG 0 vs ECOG 1-2, respectively. 6-mos PFS was 62% in MGMT+ vs 33% in MGMT- (p = 0.4) and 75% in ABCG2+ vs 50% in ABCG2- (p = 0.7). Median time to progression (TTP) with upfront TEMIRI was 9 months (range 5-28 months), with 1 patient with ongoing CR at 56 months; median TTP at relapse was 3 months (1-29 months). MGMT and ABCG2 expression did not influence 1-yr OS, whereas ECOG (0 vs 1-2) did (88% vs 31% p < 0.001). Grade 3-4 diarrhea, neutropenia, and thrombocytopenia incidence was < 5%, 1 patient with recurrent kidney EWS died of acute liver failure. Conclusions: TEMIRI showed promising activity in a very unfavorable cohort of EWS patients, with manageable toxicity. Performance status correlated with 6-month PFS & OS whereas MGMT & ABCG2 did not. Clinical trial information: NCT03542097 .

Purpose: Osteosarcoma (OS) is the most common primary bone tumor. Despite complete surgical removal and intensive chemotherapeutic treatment, 30%-35% of patients with OS have local or systemic recurrence. Some patients survive multiple recurrences, but overall survival after OS recurrence is poor. This analysis aims to describe and identify factors influencing post-relapse survival (PRS) after a second OS relapse. Methods: This is a retrospective analysis of 60 patients with a second relapse of OS of the extremities in 2 Italian centers between 2003 and 2013. Results: Treatment for first and subsequent relapses was planned according to institutional guidelines. After complete surgical remission (CSR) following the first recurrence, patients experienced a second OS relapse with a median disease-free interval (DFI) of 6 months. Lung disease was prevalent: 44 patients (76%) had pulmonary metastases. Survival after the second relapse was 22% at 5 years. Lung disease only correlated with better survival at 5 years (33.6%) compared with other sites of recurrence (5%; p = 0.008). Patients with a single pulmonary lesion had a better 5-year second PRS (42%; p = 0.02). Patients who achieved a second CSR had a 5-year second PRS of 33.4%. Chemotherapy (pConclusions: This analysis confirms the importance of an aggressive, repeated surgical approach. Lung metastases only, the number of lesions, DFI and CSR influenced survival. It also confirms the importance of chemotherapy in patients in whom surgical treatment is not feasible.

Purpose: Aneurysmal bone cyst (ABC) is a rare skeletal tumor usually treated with surgery/embolization. We hypothesized that owing to similarities with giant cell tumor of bone (GCTB), denosumab was active also in ABC. Methods: In this observational study, a retrospective analysis of ABC patients treated with denosumab was performed. Patients underwent radiologic disease assessment every 3 months. Symptoms and adverse events were noted. Results: Nine patients were identified (6 male, 3 female), with a median age of 17 years (range 14–42 years). Primary sites were 6 spine–pelvis, 1 ulna, 1 tibia, and 1 humerus. Patients were followed for a median time of 23 months (range 3–55 months). Patients received a median of 8 denosumab administrations (range 3–61). All symptomatic patients had pain relief and 1 had paresthesia improvement. Signs of denosumab activity were observed after 3 to 6 months of administration: bone formation by computed tomography scan was demonstrated in all patients and magnetic resonance imaging gadolinium contrast media decrease was observed in 7/9 patients. Adverse events were negligible. At last follow-up, all patients were progression-free: 5 still on denosumab treatment, 2 off denosumab were disease-free 11 and 17 months after surgery, and the last 2 patients reported no progression 12 and 24 months after denosumab interruption and no surgery. Conclusions: Denosumab has substantial activity in ABCs, with favorable toxicity profile. We strongly support the use of surgery and/or embolization for the treatment of ABC, but denosumab could have a role as a therapeutic option in patients with uncontrollable, locally destructive, or recurrent disease.

Background: Data on temozolomide (TEM) and irinotecan (IRI) activity in recurrent Ewing sarcoma (EWS), especially in adult patients, are limited. Methods: Patients receiving TEM 100 mg/m2/day oral, and IRI 40 mg/m2/day intravenous, days 1–5, every 21 days, were included in this multi-institutional retrospective study. Disease control rate (DCR) [overall response rate (ORR) [complete response (CR) + partial response (PR)] + stable disease (SD)], 6-months progression-free survival (6-mos PFS) and 1-year overall survival (OS) were assessed. Results: The median age of the 51 patients was 21 years (range 3–65 years): 34 patients (66%) were adults (≥18 years of age), 24 (48%) had ECOG 1 and 35 (69%) were presented with multiple site recurrence. TEMIRI was used at first relapse/progression in 13 (25%) patients, while the remainder received TEMIRI for second or greater relapse/progression. Fourteen (27%) patients had received prior myeloablative therapy with busulfan and melphalan. We observed five (10%) CR, 12 (24%) PR and 19 (37%) SD, with a DCR of 71%. 6-mos PFS was 49% (95% CI 35–63) and it was significantly influenced by ECOG (6-mos PFS 64% [95% CI 45–83] for ECOG 0, 34% [95% CI 14–54] for ECOG ≥1; p =.006) and LDH (6-mos PFS 62% [95% CI 44–79] for normal LDH, 22% [95% CI 3–42] for high LDH; p =.02), with no difference according to line of treatment, age and metastatic pattern. One-year OS was 55% (95% CI 39–70), with RECIST response (p =.001) and ECOG (p =.0002) independently associated with outcome. Grade 3 and 4 toxicity included neutropenia in 12% of patients, thrombocytopenia in 4%, diarrhea in 4%. Conclusions: This series confirms the activity of TEMIRI in both adults and pediatric patients. This schedule offers a 71% DCR, independently of the line of chemotherapy. Predictive factors of response are ECOG and LDH.

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.

In patients with relapsed osteosarcoma, the surgical excision of all metastases, defined as second complete remission (CR-2), is the factor that mainly influences post-relapse survival (PRS). Currently a validated follow-up policy for osteosarcoma is not available, both chest X-ray and computed tomography (CT) are suggested for lung surveillance. The purpose of this study is to evaluate whether the type of imaging technique used for chest surveillance, chest X-ray or CT, influenced the rate of CR-2 and prognosis in patients with recurrent osteosarcoma.Patients up to 40 years with extremity osteosarcoma enrolled in consecutive clinical trials and treated at the Rizzoli Institute from 1986 to 2009 were identified. Only patients who had lung metastases alone as first pattern of recurrence were considered for the analysis. The rate of CR-2, overall survival (OS) and PRS were the end-points of the study.The median follow-up was 47 months (1-300), 215 patients were eligible. Lung metastases were detected by chest X-ray in 100 (47%) patients, by CT in 112 (52%) and by symptoms in 3 (1%). CR-2 rate was 60% for patients followed by X-rays and 88% for those followed by CT (p .0001). 5-year PRS was 30% (95% CI 21-39) in the X-ray group and 49% (95% CI 39-59) in the CT group (p = .0004). 5-year OS was 35% (95% CI 26-44) in the X-ray group and 60% (95% CI 51-70) in the CT group (p = .004).A follow-up strategy with chest CT leads to a higher rate of CR-2 and significantly improves PRS and OS in osteosarcoma, compared to chest X-ray.

11030 Background: TMZ+IRI has significant activity in metastatic ES. Epigenetic silencing of the MGMT DNA gene by promoter methylation has been associated with response to TMZ in glioblastoma. Our aim was to assess if MGMT methylation 1) has a role in ES progression and 2) is predictive of response to TMZ. Methods: 1) In 10 ES cell lines presence of MGMT gene (Real-time PCR), methylation of its promoter (methylation-specific PCR) and protein expression (western blot) were assessed. MGMT protein (IHC) and methylation of its promoter was searched in 97 ES pts samples (74 localized; 23 metastatic). 2) In metastatic ES pts treated with TMZ+IRI, with pre-treatment FFPE tissue and measurable disease, the relation between RECIST response, PFS and MGMT expression (IHC) was assessed. Results: 1) The expression of MGMT gene and its protein was detected and concordant (p = 0.02) in all ES cell lines evaluated; methylation was a rare event. In ES tissue samples the methylation of the MGMT gene was found at a low intensity as compared with the unmethylated gene, but the protein expression was relatively low: 36% in localized, 65% in metastatic pts (p 0.03). 2) 24 pts (median age 19 years, range 3-50 years; F/M: 7/17) treated with TMZ + IRI from 2010 to 2015 were identified. Line of treatment: 8 patients were in 1st line; 16 ≥ 2nd line. Median n of cycles was 6 (range: 2-31). Pattern of metastases: 16 multiple sites, 4 lungs, 3 multiple sites + bone marrow, 1 bone. MGMT was positive in 63% of cases. ORR: 16.5% (1 CR , 3 PR); SD: 50% (13 pts); PD: 33.5% (7 pts). According to MGMT expression the ORR was 11% in negative and 20% in MGMT positive patients (p = 0.8). 6-mos PFS rate was 59% (38-80 %IC), no differece according to MGMT expression (pos 61% vs neg 56%, p 0.7). Conclusions: Whereas in cell lines the MGMT gene and its protein expression is a generalized event, in tissue samples MGMT protein is present in a minority of localized pts, and might be associate with tumor progression. Methylation of MGMT gene does not seem responsible for its regulation in ES, and post-transcriptional mechanisms are more likely to be involved. The presence of MGMT protein does not predict the response to TMZ + IRI in this small series.

Purpose Patients with Ewing sarcoma who are 40 years old or older are usually excluded from clinical trials. For this reason, information on this subset of patients is limited. Methods Clinical characteristics and treatment-related variables of patients aged 40 years or more, with a diagnosis of Ewing sarcoma, treated at the authors’ institution had been prospectively collected since 1999. Results Thirty-one patients were identified, with ages ranging from 40 to 70 years (median 45 years). Twenty-six (84%) had localized disease, 4 patients presented with lung metastases, and 1 patient had multiple metastases (bone, lung, abdominal nodes, and bone marrow). The primary tumors were skeletal in 19 (61%) patients, while 12 (39%) had extraskeletal disease. All patients received chemotherapy according to regimens similar to those adopted in younger patients, based on doxorubicin, cyclophosphamide, etoposide, vincristine, dactinomycin, and ifosfamide. All patients experienced grade 4 leukopenia (100%); red blood cells or platelets transfusions were needed in 50% and 16% of patients, respectively. Toxicity-related dose reduction was required in 13 patients (43%). The 5-year overall survival (OS) was 54% for the whole group. In patients with complete remission, 5-year disease-free survival was 57%. Survival was different for patients with skeletal and extraskeletal Ewing sarcoma (5-year OS: 64% vs 40%, p = 0.2). Conclusions In older patients, the incidence of extraskeletal Ewing sarcoma is high. Intensive chemotherapy treatment can be recommended in this group. The high chemotherapy toxicity can be justified by expected results, similar to those of younger patients.

10541 Background: The prognosis of relapsed and unresectable high-grade osteosarcoma is poor and has remained unchanged for decades. Increased survival for metastatic soft tissue sarcomas was previ...

Influence of age and sex on chemotherapy-related toxicity was evaluated in children (3-9 years), adolescents (10-17 years), and adults (up to 40 years) with localized Ewing sarcoma (ES) enrolled in the ISG/SSG III protocol. Treatment was based on vincristine, doxorubicin, cyclophosphamide, ifosfamide, dactinomycin, and etoposide. High-dose chemotherapy with busulfan and melphalan was given in poor responder patients. The analysis was based on 2191 courses of standard chemotherapy and 230 patients. A lower risk of G4 leukopenia and thrombocytopenia, hospitalization, febrile neutropenia, and red blood cell (RBC) transfusions was observed in males. Use of granulocyte colony-stimulating factor (G-CSF) was more frequent in adults, while children more often received RBC transfusions. A significant correlation between sex and chemotherapy-related toxicity was observed in the study, whereas no significant differences in terms of bone marrow toxicity can be expected according to patient age. Further studies should analyse the role of pharmacokinetics, pharmacogenomics, and clinical characteristics. © 2014 Edizioni Scientifiche per l'Informazione su Farmaci e Terapia.

Background: Few new compounds are available for relapsed osteosarcoma. We retrospectively evaluated the activity of gemcitabine (G) plus docetaxel (D) in patients with relapsed high-grade osteosarcoma and high-grade spindle cell sarcoma of bone (HGS). Methods: Patients receiving G 900 mg/m2 d 1, 8; D 75 mg/m2 d 8, every 21 days were eligible. Primary end-point: progression-free survival (PFS) at 4 months; secondary end-point: overall survival (OS) and response rate. Results: Fifty-one patients were included, with a median age of 17 years (8-71), 26 (51 %) were pediatric patients. GD line of treatment: 2nd in 14 patients, ≥3rd in 37. 25 (49 %) patients had metastases limited to lungs, 26 (51 %) multiple sites. Histology: 40 (78 %) osteosarcoma, 11 (22 %) HGS. Eight (16 %) patients achieved surgical complete response (sCR2) after GD. Four-month PFS rate was 46 %, and significantly better for patients with ECOG 0 (ECOG 0: 54 % vs ECOG 1: 43 % vs ECOG 2: 0 %; p = 0.003), for patients undergoing metastasectomy after GD (sCR2 75 % vs no-sCR2 40 %, p = 0.02) and for osteosarcoma (osteosarcoma 56 % vs HGS 18 %; p = 0.05), with no differences according to age, line of treatment, and pattern of metastases. Forty-six cases had RECIST measurable disease: 6 (13 %) patients had a partial response (PR), 20 (43 %) had stable disease (SD) and 20 (43 %) had progressive disease (PD). The 1-year OS was 30 %: 67 % for PR, 54 % for SD and 20 % for PD (p = 0.005). Conclusions: GD is an active treatment for relapsed high-grade osteosarcoma, especially for ECOG 0 patients, and should be included in the therapeutic armamentarium of metastatic osteosarcoma.

e23501Background: Osteosarcoma is a rare disease recurring mainly to the lungs. In unoperable cases high dose ifosfamide, gemcitabine/docetaxel, /etoposide are employed. Very few studies are availa...

Aims and backgroundTo investigate a six-drug combination in patients with non-metastatic Ewing sarcoma, focusing on chemotherapy-induced necrosis and chemotherapy toxicity in adult and pediatric patients.Methods and study designAlternating cycles of vincristine (1.5 mg/m2), doxorubicin (80 mg/m2) and cyclophosfamide (1200 mg/m2) (weeks 0, 6, 13, 22a nd 31), ifosfamide (9 g/m2), vincristine (1.5 mg/m2), and actinomycin D (1.5 mg/m2) (weeks 3, 16, 25 and 34), and ifosfamide (9 g/m2) and etoposide (450 mg/m2) (weeks 9, 19, 28 and 37) were administered. Primary chemotherapy-induced necrosis was graded: G3 (complete necrosis), G2 (microfoci of tumor cells) and G1 (macrofoci of tumor cells).ResultsFrom 1996 to 1999, 50 patients with Ewing sarcoma were enrolled. The median age was 23.5 years (range, 4–56). Chemotherapy-induced necrosis (in 28 patients) was G3 in 36%, G2 in 21% and G1 in 43%. At a median follow-up of 110 months (range, 36–129), 5-year overall survival and event-free survival were 72% and 66%, respectively. According to histologic response, 5-year event-free survival was 90% in G3, 83% in G2, and 42% in G1 (P = 0.02). In adult and pediatric (ConclusionsThe six-drug combination can be administered safely in adult and pediatric populations. About 40% of patients have a poor chemotherapy-induced tumor necrosis, leading to poor probability of survival. New strategies are recommended to improve survival of poor responders to the six-drug combination.

A correlation between chemotherapy-induced necrosis and prognosis has been reported in Ewing sarcoma. To identify factors influencing histologic response data from 122 patients with Ewing sarcoma surgically treated were reviewed. Primary chemotherapy was based on vincristine, doxorubicin, cyclophosphamide, ifosfamide, actinomycin-D, and etoposide. Patients with complete necrosis or only scattered foci of viable tumor cells were good responders (GRs), the remaining patients poor responders (PRs). Age, sex, site and size of the tumor, fever at diagnosis, and lactate dehydrogenase level were clinical variables investigated. Mean age was 13.3±6 in GR and 18.1±9 in PR (P18 years (P=0.003). Female were more likely to achieve a GR (F 64% vs. M 42%, P

11033Background: Treatment of patients with metastatic Ewing sarcoma (ES) remains a challenge. Pre-clinical studies and small retrospective series, mainly including pediatric patients, have demonst...

10527 Background: Although there are many reports on post-relapse survival for osteosarcoma,studies on validated clinical outcome measures (progression-free survival at 6 months [6-mo PFS], complet...

Clinicopathologic variables associated with a good histological response to primary chemotherapy in Ewing's sarcoma are identified. The histological response to preoperative chemotherapy in 243 cases of Ewing's sarcoma treated with neoadjuvant chemotherapy was analyzed in relation to different clinicopathological features (sex and age of the patients, tumor size, serum lactate dehydrogenase (LDH) levels, tumor site) and to the type and schedule of anticancer drugs delivered preoperatively according to three consecutive chemotherapy regimens. A higher rate of good responses was achieved with the use of ifosfamide and dactinomycin in addition to a conventional three-drug VAC regimen, suggesting that these drugs should be included from the beginning in neoadjuvant regimens for the treatment of Ewing's sarcoma. The analysis of event-free survival in 158 patients with a 4-year minimum follow-up confirmed that histological response to preoperative chemotherapy is a reliable predictor of outcome in Ewing's sarcoma.

Eighteen patients with high grade malignant fibrous histiocytoma (MFH) of bone and 112 patients with high grade osteosarcoma (OS) of the extremity were treated with neoadjuvant chemotherapy comprised of methotrexate, cisplatinum, doxorubicin and ifosfamide. For the 18 patients with MFH, surgery involved amputation in 2 cases and limb salvage in 16 (89%); the 112 osteosarcoma patients had amputation in 8 cases and limb salvage procedure in 104 cases (93%). The rate of good histologic response to preoperative chemotherapy (90% or more tumor necrosis) was significantly higher in patients with osteosarcoma than in patients with MFH (74% vs 28%; p < 0.003). However, at a median follow-up of 38 months (range 25-61), the 3-year event-free survival (EFS) did not differ in the two groups (MFH 77.8%, OS 70.5%; p = ns). In patients with MFH, no local recurrences were registered, whereas in the osteosarcoma group there were 6 local relapses (5.%). The effectiveness of neoadjuvant chemotherapy in the treatment of osteosarcoma has been assessed during the last 15 years. The results of the present study seem to indicate that, in spite of a usually poor histologic response to preoperative treatment, neoadjuvant chemotherapy is very effective also in MFH of bone.

BACKGROUND:: The incidence of central venous catheter (CVC)-related complications reported in pediatric sarcoma patients is not established as reports in available literature are limited. The analysis of risk factors is part of the strategy to reduce the incidence of CVC complications. OBJECTIVE:: The objective of this study was to determine the incidence of CVC complications in children with bone sarcomas and if defined clinical variables represent a risk factor. METHODS:: During an 8-year period, 155 pediatric patients with bone sarcomas were prospectively followed up for CVC complications. Incidence and correlation with clinical features including gender, age, body mass index, histology, disease stage, and use of thromboprophylaxis with low-molecular-weight heparin were analyzed. RESULTS:: Thirty-three CVC complications were recorded among 42 687 CVC-days (0.77 per 1000 CVC-days). No correlation between the specific clinical variables and the CVC complications was found. A high incidence of CVC-related sepsis secondary to gram-negative bacteria was observed. CONCLUSIONS:: The analysis of CVC complications and their potential risk factors in this sizable and relatively homogeneous pediatric population with bone sarcomas has led to the implementation of a multimodal approach by doctors and nurses to reduce the incidence and morbidity of the CVC-related infections, particularly those related to gram-negative bacteria. IMPLICATIONS FOR PRACTICE:: As a result of this joint medical and nursing study, a multimodal approach that included equipping faucets with water filters, the reeducation of doctors and nurses, and the systematic review of CVC protocol was implemented. © 2014 Wolters Kluwer Health Lippincott Williams & Wilkins.

Background Dermatofibrosarcoma protuberans (DFSP) is a relatively common soft-tissue tumor. A more aggressive appearing fibrosarcoma may arise in DFSP, changing its biological behavior. CD34 and apolipoprotein-D are highly expressed in DFSP, but their prognostic significance is uncertain. Methods DFSP and fibrosarcomatous-DFSP (FS-DFSP) patients referred to our institute between 1982 and 2009 were identified. Fibrosarcomatous changes, expression of CD34 and apolipoprotein-D were evaluated. Results 40 patients, (median age 43 years, 55% males) were identified. Tumor was located in the limbs in 60%, in the trunk in 40%. Thirty-seven patients had localized and 3 had metastatic disease. Thirteen (32%) patients were FS-DFSP. All but one underwent surgery with adequate surgical margins in 72%. 7 FS-DFSP received also radiotherapy (RT). Chemotherapy was administered to 3 patients with FS-DFSP. With a median follow-up of 49 months, the 5-OS was 90%. Local recurrence rate was 23%: 42% FS-DFSP, 15% DFSP. Metastases developed in three FS-DFSP patients. The 5-year EFS was 70% in localized patients. Histology (DFSP 75% vs. FS-DFSP 52%, p = 0.002), surgical margins (adequate 74% vs. inadequate 55%, p = 0.02), site (limb 47% vs. trunk 100%), CD34 expression (CD34 positive: 70% vs. CD34 negative: 33%, p = 0.05), and apolipoprotein-D expression (Apo-D positive: 73% vs. Apo-D negative: 33%, p = 0.02) influenced the 5-year EFS, whereas sex, use of RT or number of previous surgical treatments did not. Conclusions Patients with DFSP have a high survival probability. Site, adequate surgical margins, presence of the fibrosarcomatous component, lack of CD34 expression and apolipoprotein-D influence outcome.

BACKGROUND: Periosteal osteosarcoma is a rare variant of osteosarcoma. Wide surgical removal is the mainstay of treatment, but controversy remains about the role of chemotherapy. The objective of this study was to review and analyze the clinical and treatment-related factors that influence the survival of patients with periosteal osteosarcoma who received treatment in a single institution. METHODS: Thirty-three patients with periosteal osteosarcoma (19 males and 14 females) with a median age of 16 years (range, ages 6-32 years) underwent surgery (32 patients) and received radiotherapy (1 patient). Chemotherapy was received according to different regimens for high-grade osteosarcoma by 14 patients who had grade 3 tumors. RESULTS: The 10-year overall survival rate was 84%. The only patient who did not undergo surgery died of disease after 9 months; for the remaining 32 patients the 10-year disease-free survival rate was 65%. Survival was not influenced by the receipt of chemotherapy. The patients who received chemotherapy had a 10-year overall survival rate of 86%, and those who received only local treatment had an overall survival rate of 83% (P ¼ .73). CONCLUSIONS: The authors’ experience indicated that the treatment of periosteal osteosarcoma requires only wide surgical removal of the tumor and that adjuvant chemotherapy does not improve survival. Cancer 2010;000:000–000. V C 2010 American Cancer Society.