Publications by authors named "Alessandra Longhi"

86 Publications

Predictors of lung recurrence and disease-specific mortality after pulmonary metastasectomy for soft tissue sarcoma.

Surg Oncol 2021 Feb 20;37:101532. Epub 2021 Feb 20.

Cardiovascular Research Institute Maastricht - CARIM, Maastricht University Medical Center, the Netherlands. Electronic address:

Background: We identified prognostic factors in a 30-year series of STS treated at a single Institution, using an advanced statistical approach.

Methods: From June 1988 to July 2019, 164 patients were referred to Rizzoli Orthopedic Hospital, Bologna, Italy) for STS lung metastasectomy (LMTS). The endpoints were lung metastasis recurrence (LMR) and lung metastasis-specific mortality (LMSM). The analysis included directed acyclic graphs, cubic splines, and a competing risk model in order to minimize bias.

Results: The 10- and 15- year LMR cumulative incidence were 0.77 (0.76-0.78) whereas 10- and 15- year freedom from LMSM were 0.60 [0.51-0.70] and 0.56 [0.47-0.67], respectively. The malignant peripheral nerve sheath tumor (MPNST) histotype (SHR 4.12 [2.05-8.27]), a disease-free interval (DFI) up to 68 months (HR from 2 [1.7-2.2] to 1.5 [1.1-1.9]) and a LM size ≥4 mm (3.1 [2.1-4.4]) predicted LMR. Myxofibrosarcoma (HR 2.52[1.64-3.86]), synovial sarcoma (2.53[1.22-5.23]), adjuvant chemotherapy (2.01[1.11-3.61]), DFI between 2 months and 20 months (HR from 1.5 [1.1-2.3] to 1.3 [1.1-1.7] and primary tumor size a primary tumor size comprised between 3.6 cm and 10 cm predicted LMSM. A sharp increase in LMSM was observed with a tumor size from ≥20 cm.

Conclusions: Our analysis corrected by potential confounders allowed us to identify specific histotypes and DFI intervals as predictors of both LMR and LMSM. Tumor size adjuvant chemotherapy adversely affected LM-related survival. Our findings need to be confirmed by larger randomized studies.
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http://dx.doi.org/10.1016/j.suronc.2021.101532DOI Listing
February 2021

Histological response to neoadjuvant chemotherapy in localized Ewing sarcoma of the bone: A retrospective analysis of available scoring tools.

Eur J Surg Oncol 2021 Feb 16. Epub 2021 Feb 16.

Department of Pathology, Azienda Ospedaliera di Padova, Padua, Italy.

Aim: The aim is to evaluate which of the existing scoring systems of histological response to neoadjuvant chemotherapy best stratifies the clinical outcome of patients with localized Ewing sarcoma of bone.

Methods: 474 patients with diagnosis of localized Ewing sarcoma of bone were included. The median follow-up was 13.5 years.

Results: The overall survival and the disease-free survival (DFS) were 70.8% and 63.9% at 5 years. The percentage of histological response to neoadjuvant chemotherapy ranged between 5% and 100% (mean 83%). The agreement between Bologna System and the different percentual cut-offs of histological response to neoadjuvant chemotherapy was high, with kappa statistics of 0.83 for a cut-off of ≥90%; 0.86 for a cut-off of ≥95%; 0.79 for a cut-off of ≥96% and 0.61 for a cut-off of 100%. Statistically higher DFS rates for good responders compared to poor responders were found when using each given system. Model performance indicators showed that Bologna system had a lower AIC score and a higher c-statistics to predict DFS. When the patients classified as good responders using the different percentual cut-offs of histological response to neoadjuvant chemotherapy, were instead re-classified using the Bologna system, statistical differences were noted in DFS within each specific group.

Conclusions: All scoring tools to evaluate histological response to neoadjuvant chemotherapy offer good predictive value for DFS in localized Ewing's sarcoma of bone. The Bologna system better stratifies those patients with histological response to neoadjuvant chemotherapy between 90 and 99%, representing a more reliable scoring tool in this subset.
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http://dx.doi.org/10.1016/j.ejso.2021.02.009DOI Listing
February 2021

Pembrolizumab in advanced osteosarcoma: results of a single-arm, open-label, phase 2 trial.

Cancer Immunol Immunother 2021 Feb 12. Epub 2021 Feb 12.

IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.

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.
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http://dx.doi.org/10.1007/s00262-021-02876-wDOI Listing
February 2021

Exploring Metabolic Adaptations to the Acidic Microenvironment of Osteosarcoma Cells Unveils Sphingosine 1-Phosphate as a Valuable Therapeutic Target.

Cancers (Basel) 2021 Jan 15;13(2). Epub 2021 Jan 15.

Biomedical Science and Technology Lab, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy.

Acidity is a key player in cancer progression, modelling a microenvironment that prevents immune surveillance and enhances invasiveness, survival, and drug resistance. Here, we demonstrated in spheroids from osteosarcoma cell lines that the exposure to acidosis remarkably caused intracellular lipid droplets accumulation. Lipid accumulation was also detected in sarcoma tissues in close proximity to tumor area that express the acid-related biomarker LAMP2. Acid-induced lipid droplets-accumulation was not functional to a higher energetic request, but rather to cell survival. As a mechanism, we found increased levels of sphingomyelin and secretion of the sphingosine 1-phosphate, and the activation of the associated sphingolipid pathway and the non-canonical NF-ĸB pathway, respectively. Moreover, decreasing sphingosine 1-phosphate levels (S1P) by FTY720 (Fingolimod) impaired acid-induced tumor survival and migration. As a confirmation of the role of S1P in osteosarcoma, we found S1P high circulating levels (30.8 ± 2.5 nmol/mL, = 17) in the serum of patients. Finally, when we treated osteosarcoma xenografts with FTY720 combined with low-serine/glycine diet, both lipid accumulation (as measured by magnetic resonance imaging) and tumor growth were greatly inhibited. For the first time, this study profiles the lipidomic rearrangement of sarcomas under acidic conditions, suggesting the use of anti-S1P strategies in combination with standard chemotherapy.
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http://dx.doi.org/10.3390/cancers13020311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830496PMC
January 2021

Upfront surgery is not advantageous compared to more conservative treatments such as observation or medical treatment for patients with desmoid tumors.

BMC Musculoskelet Disord 2021 Jan 5;22(1):12. Epub 2021 Jan 5.

Department of Orthopaedic Oncology, IRCCS Istituto Ortopedico Rizzoli, Via Pupilli 1, 40136, Bologna, Italy.

Background: This 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.

Methods: We 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.

Results: An 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).

Conclusion: Upfront surgery is not advantageous compared to more conservative treatments such as observation or medical treatment for patients with desmoid tumors.
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http://dx.doi.org/10.1186/s12891-020-03897-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7784367PMC
January 2021

Outcome of lung metastases due to bone giant cell tumor initially managed with observation.

J Orthop Surg Res 2020 Nov 7;15(1):510. Epub 2020 Nov 7.

Orthopaedic Service, IRCCS Istituto Ortopedico Rizzoli, Via Pupilli 1, 40136, Bologna, Italy.

Background: The outcomes of patients with lung metastases from giant cell tumor of bone (GCTB) vary from spontaneous regression to uncontrolled growth. To investigate whether observation is an appropriate first-line management approach for patients with lung metastases from GCTB, we evaluated the outcomes of patients who were initially managed by observation.

Methods: We retrospectively reviewed the data of 22 patients with lung metastases from histologically confirmed GCTB who received observation as a first-line treatment approach. The median follow-up period was 116 months.

Results: Disease progression occurred in 12 patients (54.5%). The median interval between the discovery of lung metastases and progression was 8 months. Eight patients underwent metastasectomy following initial observation. The median interval between the discovery of lung metastases and treatment by metastasectomy was 13.5 months. None of the patients experienced spontaneous regression. Of the 22 patients, 36.4% needed a metastasectomy, and 9.1% required denosumab treatment during the course of the follow-up period. Disease progression occurred in 45.5% of the 11 patients with lung nodules ≤ 5 mm, while all five of the patients with lung nodules > 5 mm experienced disease progression. Progression-free survival was significantly worse in the group with lung nodules > 5 mm compared to the group with lung nodules ≤ 5 mm (p = 0.022).

Conclusions: Observation is a safe first-line method of managing patients with lung metastases from GCTB. According to radiological imaging, approximately half of the patients progressed, and approximately half required a metastasectomy or denosumab treatment. However, patients with lung nodules > 5 mm should receive careful observation because of the high rate of disease progression in this group.
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http://dx.doi.org/10.1186/s13018-020-02038-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648999PMC
November 2020

High Dose Ifosfamide in Relapsed and Unresectable High-Grade Osteosarcoma Patients: A Retrospective Series.

Cells 2020 10 31;9(11). Epub 2020 Oct 31.

Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy.

: 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. : Patients with osteosarcoma relapsed after standard treatment [methotrexate, doxorubicin, cisplatin +/- ifosfamide (MAP+/-I)] with measurable disease according to RECIST1.1 were eligible to ifosfamide (3 g/m/day) continuous infusion (c.i.) days 1-5 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. : 51 patients were included. ORR was 20% (1 CR + 9 PR). Median DOR was 5 months (95%CI 2-7). Median PFS, 6m-PFS, OS, and 2y-OS were 6 months (95%CI 4-9), 51%, 15 months (10-19), 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, = 0.034) and CR2 (HR 0.126, < 0.001) showed a significant correlation with PFS and OS, respectively. No significant correlation was found between outcomes and PARP1 or gene mutations. : HD-IFO should be considered as the standard first-line treatment option in relapsed osteosarcoma and control arm of future trial in this setting.
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http://dx.doi.org/10.3390/cells9112389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692098PMC
October 2020

MRI Features as Prognostic Factors in Myxofibrosarcoma: Proposal of MRI Grading System.

Acad Radiol 2020 Sep 11. Epub 2020 Sep 11.

Department of Orthopaedics, AOSP Sant'Orsola Malpighi, Bologna, Italy.

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 < 0.001).

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.
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http://dx.doi.org/10.1016/j.acra.2020.08.018DOI Listing
September 2020

Chondroblastoma's Lung Metastases Treated with Denosumab in Pediatric Patient.

Cancer Res Treat 2021 Jan 6;53(1):279-282. Epub 2020 Aug 6.

Chemotherapy Division, IRCCS, Istituto Ortopedico Rizzoli, Bologna, Italy.

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.
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http://dx.doi.org/10.4143/crt.2020.384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812007PMC
January 2021

Cross-Cultural Validation of the Italian Version of the Bt-DUX: A Subjective Measure of Health-Related Quality of Life in Patients Who Underwent Surgery for Lower Extremity Malignant Bone Tumour.

Cancers (Basel) 2020 Jul 23;12(8). Epub 2020 Jul 23.

Servizio di Assistenza Infermieristica, Tecnica e Riabilitativa, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy.

The purpose of this study was to translate the English bone tumour DUX (Bt-DUX-Eng) questionnaire for lower extremity bone tumour patients, a disease-specific quality of life (QoL) instrument, into Italian and then examine the validity of the Italian version of Bt-DUX (Bt-DUX-It). The adaptation and translation process included forward translation, back-translation, and a review of the back-translation by an expert committee. The Bt-DUX-It was validated in a sample of adolescents treated for lower extremity osteosarcoma in Italy. Assessments included the Bt-DUX, the Toronto Extremity Salvage Score (TESS), and the European Organization for Research and Treatment Core Quality of Life Questionnaire of Cancer Patients (EORTC QLQ-C30). Fifty-one patients with a median age of 20 years (range: 15-25) completed the questionnaires. The mean Bt-DUX score was 70 (range: 16.30-100). The internal consistency of the overall score and that of the Bt-DUX-It was good: Cronbach's α was 0.95. Spearman's correlation coefficient between the Bt-DUX (total and domain scores) and EORTC QLQ C30 and TESS were overall moderate to good, reaching a -value <0.01 in all cases. The Bt-DUX-It version is a useful tool for measuring QoL in patients with bone tumour and has similar internal consistency, construct validity, and discrimination as those of the Dutch and English versions.
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http://dx.doi.org/10.3390/cancers12082015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465526PMC
July 2020

Role of (Neo)adjuvant Denosumab for Giant Cell Tumor of Bone.

Curr Treat Options Oncol 2020 07 4;21(8):68. Epub 2020 Jul 4.

Orthopaedic Surgery, UC Davis, Sacramento, USA.

Opinion Statement: Denosumab is a RANK ligand inhibitor approved for the treatment of giant cell tumor of bone. While the role of denosumab in the setting of advanced and unresectable disease is well established, its role in surgically resectable disease is currently under discussion. Several prospective and retrospective series on neoadjuvant therapy in potentially resectable tumor with high morbidity surgery reported a relapse rate of 10-20% after resection and 30-40% after curettage. At the same time, less morbid surgery has obvious clinical advantages for the patient, and several studies have shown the efficacy of denosumab in downgrading of the surgical procedure. Currently, the role of neoadjuvant denosumab in operable GCTB is limited to selected cases in which a diffuse reactive bone formation and peripheral ossification can make an easier surgical procedure, for example, in tumors with a large soft tissue component. A planned resection may become less morbid when preoperative denosumab is administered. Whenever a segmental resection is thought to be indicated at diagnosis, denosumab may be considered in the neoadjuvant setting. A preoperative course of 6 months is considered safe and effective. Two case scenarios are presented and critically discussed. Because of the high recurrence rates after denosumab treatment followed by curettage, we discourage the use of denosumab when curettage is considered feasible. In this setting, a short course of preoperative denosumab (2-6 months) may be considered for highly selected cases, for example in pathological fractures. The role of adjuvant denosumab needs further investigation. Long-term disease control has been reported in case of non-surgical lesions, even after treatment interruption, but there is no consensus on ideal treatment duration and dosage for these scenarios. In all cases, multidisciplinary discussion with oncology, pathologist, radiologist, and surgeons is mandatory. Patient's comorbidities, dental conditions, and preferences, including family planning, should always be taken into account.
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http://dx.doi.org/10.1007/s11864-020-00766-4DOI Listing
July 2020

Extraskeletal Myxoid Chondrosarcoma with Molecularly Confirmed Diagnosis: A Multicenter Retrospective Study Within the Italian Sarcoma Group.

Ann Surg Oncol 2021 Feb 22;28(2):1142-1150. Epub 2020 Jun 22.

Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.

Background: Extraskeletal myxoid chondrosarcoma (EMC) is a rare sarcoma of uncertain origin, marked by specific chromosomal translocations involving the NR4A3 gene, and usually characterized by an indolent course. Surgery (with or without radiotherapy) is the treatment of choice in localized disease. The treatment for advanced disease remains uncertain. In order to better evaluate prognostic factors and outcome, a retrospective pooled analysis of patients with EMC treated at three Italian Sarcoma Group (ISG) referral centers was carried out.

Methods: All patients with localized EMC surgically treated from 1989 to 2016 were identified. Diagnosis was centrally reviewed according to WHO 2013. Only patients with NR4A3 rearrangement were included.

Results: Sixty-seven patients were identified: 13 (20%) female, 54 (80%) male. Median age was 56 years (range 18-84). Numbers and type of translocation were: 50 (80%) NR4A3-EWS, 10 (16%) NR4A3-TAF15, 1 (2%) NR4A3-TCF12, and 1 (2%) NR4A3-TFG. Median follow-up was 55 months (range 2-312). Five- and ten-year overall survival rates were 94% (86-100 95%CI) and 84% (69-98 95%CI). Thirty-five (52%) patients relapsed: 9 had local recurrence (LR) and 26 had distant metastasis (5 with concomitant LR). The 5- and 10-year disease-free survival rates (DFS) were 51% (38-65 95%CI) and 20% (7-33 95%CI). Size of the primary tumor was significantly related to distant metastasis-free survival (DMFS) (p = 0.004). Patients carrying the NR4A3-EWS translocation had a trend in favor of better DFS (p = 0.08) and DMFS (p = 0.09) compared with the patients with NR4A3-TAF15.

Conclusions: Prolonged survival can be expected in patients with EMC, in spite of a high rate of recurrence. Size is significantly associated with distant relapse. The type of NR4A3 translocation could influence outcome.
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http://dx.doi.org/10.1245/s10434-020-08737-7DOI Listing
February 2021

Circulating miR34a levels as a potential biomarker in the follow-up of Ewing sarcoma.

J Cell Commun Signal 2020 Sep 5;14(3):335-347. Epub 2020 Jun 5.

Laboratory of Experimental Oncology, IRCCS Istituto Ortopedico Rizzoli, via di Barbiano 1/10, 40136, Bologna, Italy.

Appropriate tools for monitoring sarcoma progression are still limited. The aim of the present study was to investigate the value of miR-34a-5p (miR34a) as a circulating biomarker to follow disease progression and measure the therapeutic response. Stable forced re-expression of miR34a in Ewing sarcoma (EWS) cells significantly limited tumor growth in mice. Absolute quantification of miR34a in the plasma of mice and 31 patients showed that high levels of this miRNA inversely correlated with tumor volume. In addition, miR34a expression was higher in the blood of localized EWS patients than in the blood of metastatic EWS patients. In 12 patients, we followed miR34a expression during preoperative chemotherapy. While there was no variation in the blood miR34a levels in metastatic patients at the time of diagnosis or after the last cycle of preoperative chemotherapy, there was an increase in the circulating miR34a levels in patients with localized tumors. The three patients with the highest fold-increase in the miR levels did not show evidence of metastasis. Although this analysis should be extended to a larger cohort of patients, these findings imply that detection of the miR34a levels in the blood of EWS patients may assist with the clinical management of EWS.
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http://dx.doi.org/10.1007/s12079-020-00567-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7511499PMC
September 2020

Long-Term Follow-up of a Randomized Study of Oral Etoposide versus Fermentatum Pini as Maintenance Therapy in Osteosarcoma Patients in Complete Surgical Remission after Second Relapse.

Sarcoma 2020 26;2020:8260730. Epub 2020 Apr 26.

Immunoreumathology and Tissue Regeneration Laboratory, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.

Background: In relapsed osteosarcoma, the 5-yr postrelapse disease-free survival (PRDFS) rate after the second relapse is <20%. In June 2007, a randomized study was started comparing oral etoposide vs fermentatum Pini (an extract derived from the parasitic plant 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. . 10 patients received oral etoposide 50 mg/m daily for 21 days every 28 days for 6 months, and 9 patients received 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 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, =0.03). Model forecast 10-yr overall survival rates as 64% in the 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 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. as maintenance treatment after complete surgical remission in relapsed osteosarcoma should be further investigated and compared with other drugs.
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http://dx.doi.org/10.1155/2020/8260730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201820PMC
April 2020

Clinical and Radiologic Features Together Better Predict Lung Nodule Malignancy in Patients with Soft-Tissue Sarcoma.

J Clin Med 2020 Apr 23;9(4). Epub 2020 Apr 23.

Cardiovascular Research Institute Maastricht-CARIM, Maastricht University Medical Center, 6229 ER Maastricht, The Netherlands.

We test the hypothesis that a model including clinical and computed tomography (CT) features may allow discrimination between benign and malignant lung nodules in patients with soft-tissue sarcoma (STS). Seventy-one patients with STS undergoing their first lung metastasectomy were examined. The performance of multiple logistic regression models including CT features alone, clinical features alone, and combined features, was tested to evaluate the best model in discriminating malignant from benign nodules. The likelihood of malignancy increased by more than 11, 2, 6 and 7 fold, respectively, when histological synovial sarcoma sub-type was associated with the following CT nodule features: size ≥ 5.6 mm, well defined margins, increased size from baseline CT, and new onset at preoperative CT. Likewise, in the case of grade III primary tumor, the odds ratio (OR) increased by more than 17 times when the diameter of pulmonary nodules (PNs) was >5.6 mm, more than 13 times with well-defined margins, more than 7 times with PNs increased from baseline CT, and more than 20 times when there were new-onset nodules. Finally, when CT nodule was ≥5.6 in size, it had well-defined margins, it increased in size from baseline CT, and when new onset nodules at preoperative CT were concomitant to residual primary tumor R2, the risk of malignancy increased by more than 10, 6, 25 and 28 times, respectively. The combination of clinical and CT features has the highest predictive value for detecting the malignancy of pulmonary nodules in patients with soft tissue sarcoma, allowing early detection of nodule malignancy and treatment options.
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http://dx.doi.org/10.3390/jcm9041209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230600PMC
April 2020

Pexidartinib for the treatment of adult patients with symptomatic tenosynovial giant cell tumor: safety and efficacy.

Expert Rev Anticancer Ther 2020 06 22;20(6):441-445. Epub 2020 Apr 22.

Orthopedic Oncology, IRCCS Istituto Ortopedico Rizzoli , Bologna, Italy.

Introduction: Tenosynovial giant cell tumor (TGCT) is a benign clonal neoplastic proliferation arising from the synovium often causing pain, swelling, joint stiffness, and reduced quality of life. The optimal treatment strategy in patients with diffuse-type TGCT (dt-TGCT) is evolving. Surgery is the main treatment, with a high recurrence rate and surgery-related morbidity. Radiotherapy is associated with important side effects. TGCT cells overexpress colony-stimulating factor 1 (CSF1). Pexidartinib (Turalio™) is a selective CSF1 R inhibitor, which was recently approved by the FDA for the treatment of TGCT.

Areas Covered: This article reviews the pharmacological properties, clinical efficacy, and safety of pexidartinib.

Expert Opinion: Pexidartinib was effective with an acceptable safety profile for advanced TGCT in phase I-III studies. The phase III trial (ENLIVEN) in unresectable TGCT met its primary endpoints of overall response rate. These results led to FDA approval for this TGCT population. Mixed or cholestatic hepatotoxicity was observed in rare cases. For this reason, pexidartinib is currently available only through a Risk Evaluation and Mitigation Strategy (REMS) Program in the USA. TGCT significantly impairs patients' quality of life. The approval of pexidartinib has changed the therapeutic armamentarium for this condition. However, strict monitoring of liver function is warranted.
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http://dx.doi.org/10.1080/14737140.2020.1757441DOI Listing
June 2020

Experience with eribulin in pretreated patients with advanced liposarcoma: a case series.

Future Oncol 2020 Jan 20;16(1s):25-32. Epub 2019 Dec 20.

Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.

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.
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http://dx.doi.org/10.2217/fon-2019-0599DOI Listing
January 2020

Identification of a novel fusion transcript EWSR1-VEZF1 by anchored multiplex PCR in malignant peripheral nerve sheath tumor.

Pathol Res Pract 2020 Jan 22;216(1):152760. Epub 2019 Nov 22.

Department of Pathology, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.

The aim of the study is to describe a novel genetic finding examining the molecular and pathological features of a case of malignant peripheral nerve sheath tumor occurring in the thigh of a 17-year-old male. Fusion gene detection using a next-generation sequencing-based anchored multiplex PCR technique (Archer FusionPlex Sarcoma Panel) was used to identify the novel fusion of EWSR1-VEZF1 from the frozen tumor sample. EWSR1-VEZF1 fusion is a novel molecular gene rearrangement involving exon 8 of the EWSR1 gene and exon 2 of the VEZF1 gene. Data were validated with gene sequencing and fluorescent in situ hybridization (FISH) analysis. This case report describes a novel rearrangement involving EWSR1 on chromosome 22 and VEZF1 on chromosome 17. The result obtained demonstrates the value of the next-generation sequencing-based anchored multiplex PCR technique (Archer FusionPlex Sarcoma Panel) both in diagnosis and patient care and might become a helpful diagnostic tool for this tumor type.
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http://dx.doi.org/10.1016/j.prp.2019.152760DOI Listing
January 2020

Is there a role for chemotherapy after local relapse in high-grade osteosarcoma?

Pediatr Blood Cancer 2019 08 6;66(8):e27792. Epub 2019 May 6.

Chemotherapy Unit, IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy.

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.
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http://dx.doi.org/10.1002/pbc.27792DOI Listing
August 2019

The role of 18F-FDG PET/CT in soft tissue sarcoma.

Nucl Med Commun 2019 Jun;40(6):626-631

IRCCS Rizzoli Orthopaedic Institute.

Introduction: Soft tissue sarcomas (STS) are highly fluorine-18-fluorodeoxyglucose (F-FDG)-avid tumours. PET seems to be effective for the assessment of the extent of disease. However, the use of PET to stratify STS into different risk histotypes still remains controversial. Our aim was to evaluate F-FDG uptake in different STS types and to assess the prognostic value of the maximum standardized uptake value (SUVmax).

Patients And Methods: We reviewed 50 adult patients with primary high-grade STS of the extremities with a preoperative PET. Overall survival and local recurrence were analysed.

Results: The mean SUVmax was 12.9 (range: 2.2-33.4). All cases of myxoid liposarcoma and all cases of synovial sarcoma had SUVmax of less than 10.3. A better overall survival and local recurrence were observed in patients with SUVmax of less than 10.3 (P=0.005 and 0.046, respectively).

Conclusion: SUVmax seems to be specific among different STS histotypes. PET does not seem to be useful in myxoid liposarcoma as well as synovial sarcoma as these tumours seem to have a low uptake of glucose. SUVmax might also be included as a prognostic factor.
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http://dx.doi.org/10.1097/MNM.0000000000001002DOI Listing
June 2019

Bone marrow biopsy in the initial staging of Ewing sarcoma: Experience from a single institution.

Pediatr Blood Cancer 2019 06 5;66(6):e27653. Epub 2019 Feb 5.

Chemotherapy Section, IRCCS-Rizzoli Orthopaedic Institute, Bologna, Italy.

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.
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http://dx.doi.org/10.1002/pbc.27653DOI Listing
June 2019

Pazopanib in relapsed osteosarcoma patients: report on 15 cases.

Acta Oncol 2019 Jan 12;58(1):124-128. Epub 2018 Sep 12.

d Department of Oncology , Oslo University Hospital, The Norwegian Radium Hospital , Oslo , Norway.

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http://dx.doi.org/10.1080/0284186X.2018.1503714DOI Listing
January 2019

Denosumab in patients with aneurysmal bone cysts: A case series with preliminary results.

Tumori 2018 Oct 8;104(5):344-351. Epub 2018 Aug 8.

1 Chemotherapy Unit, IRCCS, Istituto Ortopedico Rizzoli, Bologna, Italy.

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.
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http://dx.doi.org/10.1177/0300891618784808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247581PMC
October 2018

Tumoral immune-infiltrate (IF), PD-L1 expression and role of CD8/TIA-1 lymphocytes in localized osteosarcoma patients treated within protocol ISG-OS1.

Oncotarget 2017 Dec 4;8(67):111836-111846. Epub 2017 Dec 4.

Chemotherapy Unit, IRCCS, Istituto Ortopedico Rizzoli, Bologna, Italy.

Background: We hypothesized that immune-infiltrates were associated with superior survival, and examined a primary osteosarcoma tissue microarrays (TMAs) to test this hypothesis.

Methods: 129 patients (pts) with localized osteosarcoma treated within protocol ISG-OS1 were included in the study. Clinical characteristics, expression of CD8, CD3, FOXP3, CD20, CD68/CD163 (tumor associated macrophage, TAM), Tia-1 (cytotoxic T cell), CD303 (plasmacytoid dendritic cells: pDC), Arginase-1 (myeloid derived suppressor cells: MDSC), PD-1 on immune-cells (IC), and PD-L1 on tumoral cells (TC) and IC were analysed and correlated with outcome.

Results: Most of the cases presented tumor infiltrating lymphocytes (TILs) (CD3+ 90%; CD8+ 86%). Tia-1 was detected in 73% of the samples. PD-L1 expression was found in 14% patients in IC and 0% in TC; 22% showed PD-1 expression in IC.With a median follow-up of 8 years (range 1-13), the 5-year overall survival (5-year OS) was 74% (95% CI 64-85). Univariate analysis showed better 5-year OS for: a) pts with a good histologic response to neoadjuvant chemotherapy (p = 0.0001); b) pts with CD8/Tia1 tumoral infiltrates (p = 0.002); c) pts with normal alkaline phosphatas (sALP) (p = 0.04). After multivariate analysis, histologic response (p = 0.007) and CD8/Tia1 infiltration (p = 0.01) were independently correlated with survival. In the subset of pts with CD8+ infiltrate, worse (p 0.02) OS was observed for PD-L1(IC)+ cases.

Conclusions: Our findings support the hypothesis that CD8/Tia1 infiltrate in tumor microenvironment at diagnosis confers superior survival for pts with localized osteosarcoma, while PD-L1 expression is associated with worse survival.
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http://dx.doi.org/10.18632/oncotarget.22912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5762363PMC
December 2017

Sinusoidal obstruction syndrome/veno-occlusive disease after high-dose intravenous busulfan/melphalan conditioning therapy in high-risk Ewing Sarcoma.

Bone Marrow Transplant 2018 05 15;53(5):591-599. Epub 2018 Jan 15.

Unit of Internal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.

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.
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http://dx.doi.org/10.1038/s41409-017-0066-4DOI Listing
May 2018

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

Tumori 2018 Jan-Feb;104(1):30-36

7 Department of Orthopedic Pathology, HELIOS Klinikum Emil von Behring GmbH, Berlin - Germany.

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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http://dx.doi.org/10.5301/tj.5000696DOI Listing
May 2018

Erratum to: Osteosarcoma follow-up: chest X-ray or computed tomography?

Clin Sarcoma Res 2017 3;7. Epub 2017 May 3.

Chemotherapy Unit, Istituto Ortopedico Rizzoli, via Pupilli, 1, 40136 Bologna, Italy.

[This corrects the article DOI: 10.1186/s13569-017-0067-5.].
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http://dx.doi.org/10.1186/s13569-017-0073-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5415725PMC
May 2017

Osteosarcoma follow-up: chest X-ray or computed tomography?

Clin Sarcoma Res 2017 14;7. Epub 2017 Feb 14.

Chemotherapy Unit, Istituto Ortopedico Rizzoli, via Pupilli, 1, 40136 Bologna, Italy.

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.
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http://dx.doi.org/10.1186/s13569-017-0067-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5307808PMC
February 2017

Ewing sarcoma in patients over 40 years of age: a prospective analysis of 31 patients treated at a single institution.

Tumori 2016 Oct 18;102(5):481-487. Epub 2016 Jul 18.

 Chemotherapy Section, Rizzoli Orthopedic Institute, Bologna - Italy.

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.
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http://dx.doi.org/10.5301/tj.5000534DOI Listing
October 2016

Stereotactic Radiotherapy in the Treatment of Lung Metastases from Bone and Soft-tissue Sarcomas.

Anticancer Res 2015 Oct;35(10):5581-6

Radiation Oncology Unit, Bellaria Hospital, Bologna, Italy.

Background: The purpose of this study was to evaluate local control and toxicity in a group of patients treated with stereotactic body radiotherapy (SBRT) for lung metastases (LM) from bone and soft tissue sarcomas.

Patients And Methods: From October 2010 to July 2014, patients with LM from sarcomas not suitable for surgery were treated with daily cone-beam computed tomography-guided SBRT. The dose administered ranged from 30 to 60 Gy in 3-8 fractions. Acute and late toxicity were scored according to Common Terminology Criteria for Adverse Events version 4.0.

Results: A total of 24 patients with 68 LM from sarcomas were treated with SBRT. The median follow-up after SBRT was 17 months (range=11-51 months). Two-year actuarial lesion local control and overall survival were 85.9% and 66.4%, respectively. No G3 or greater acute and late toxicities were observed.

Conclusion: SBRT is a safe and effective treatment for LM from sarcoma and might be used as an alternative option in patients unfit for surgery.
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October 2015