Publications by authors named "Guido Scoccianti"

47 Publications

Salvage of limb salvage in oncological reconstructions of the lower limb with megaprosthesis: how much to push the boundaries?

Arch Orthop Trauma Surg 2021 Sep 13. Epub 2021 Sep 13.

Department of Orthopaedic Oncology and Reconstructive Surgery, Azienda Ospedaliero-Universitaria Careggi, Largo Palagi 1, 50139, Florence, Italy.

Introduction: Megaprosthesis represent the most commonly used limb salvage method after musculoskeletal tumor resections. Nevertheless, they are burdened by high complication rate, requiring several surgical revisions and eventually limb amputation. The aims of this study were to evaluate the effect of rescuing the limb with subsequent revisions on complication rates (a), incidence of amputations (b), and whether complications reduce functional outcome after the first surgical revision (c).

Materials And Methods: We retrospectively reviewed 444 lower limb megaprosthesis implanted for primary musculoskeletal tumors or metastatic lesions, from February 2000 to November 2017. 59 patients received at least one revision megaprosthesis surgery. MSTS score was used to assess final functional results. Complication-revision-amputation free survival rates were calculated both at 5 and 10 years of follow-up.

Results: Complication free survival, revision free survival and amputation free survival at 10 years were 47% and 53%, 61% and 67%, 90% and 86% among all 444 patients and the group of 59 revised patients, respectively. The incidence of further complications after the first complication was 26% in the group treated with no subsequent revision surgeries and 51% in the group with at least one revision surgery. We found a trend of inverse linear relationship between the number of complications needing subsequent revision surgeries and the final MSTS.

Conclusion: The number of further revision surgeries after limb salvage with megaprosthesis increases the incidence of complications. Repeated surgical revisions, in particular after infection, increase the amputation rate. The most frequent causes of failure were structural failures and infections. MSTS score was superior for patients undergoing limb salvage than amputees. However, MSTS progressively decreased with multiple revisions becoming inferior to the functional score of an amputated patient.
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http://dx.doi.org/10.1007/s00402-021-04165-8DOI Listing
September 2021

Soft Tissue Sarcoma: An Insight on Biomarkers at Molecular, Metabolic and Cellular Level.

Cancers (Basel) 2021 Jun 18;13(12). Epub 2021 Jun 18.

Department of Orthopaedic Oncology and Reconstructive Surgery, University of Florence, Careggi University Hospital, Largo Brambilla 3, 50134 Florence, Italy.

Soft tissue sarcomas (STSs) are a heterogeneous group of rare tumors. Although constituting only 1% of all human malignancies, STSs represent the second most common type of solid tumors in children and adolescents and comprise an important group of secondary malignancies. Over 100 histologic subtypes have been characterized to date (occurring predominantly in the trunk, extremity, and retroperitoneum), and many more are being discovered due to molecular profiling. STS mortality remains high, despite adjuvant chemotherapy. New prognostic stratification markers are needed to help identify patients at risk of recurrence and possibly apply more intensive or novel treatments. Recent scientific advancements have enabled a more precise molecular characterization of sarcoma subtypes and revealed novel therapeutic targets and prognostic/predictive biomarkers. This review aims at providing a comprehensive overview of the most relevant cellular, molecular and metabolic biomarkers for STS, and highlight advances in STS-related biomarker research.
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http://dx.doi.org/10.3390/cancers13123044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233868PMC
June 2021

Re-excision after unplanned excision of soft tissue sarcoma: A systematic review and metanalysis. The rationale of systematic re-excision.

J Orthop 2021 May-Jun;25:244-251. Epub 2021 May 14.

Department of Orthopaedic and Trauma Surgery, University of Pisa, Italy.

In Soft Tissue Sarcomas (STS) referral centre many patients have already had an incomplete tumour resection. In the majority of specimen, tumoral residual is detected and linked to a worsen prognosis. Systematic surgical re-resection of the scar tissue area is often performed. Some authors suggested to postpone re-resections until a clinically evident local recurrence is detected. A searching strategy was applied to Pubmed-Central and Ovid Medline. Odds ratio (OR) for local recurrence (LR), distant metastasis (MTS) or overall survival (OS) were calculated comparing patients who had tumour residual to people who hadn't. OR of local recurrences, distant metastasis and OS were calculated in planned vs unplanned-excisions groups. OR to develop a metastasis and OS after a local recurrences were calculated. Residual tumour led to an OR for LR of 3,56, OR of MTS was 3,42; OR of decreased OS was 3,42. Having a LR lead to a OR of 1,55 for MTS and to a OR of decreased OS of 2,32. Patients who underwent a re-excision compared to planned surgery did not have an increased OR of LR and had an OR to develop a MTS of 0,56. Our data confirm that there is a strong correlation between local recurrences, distant relapses and overall survival. Although there is a selection bias; this analysis highlights the optimal oncological outcome in patients who underwent re-resection. The rationale for systematic re-resection after unplanned excision of soft tissue sarcomas is very strong and this treatment remains the gold standard of care in these patients.
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http://dx.doi.org/10.1016/j.jor.2021.05.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165293PMC
May 2021

Extra-abdominal desmoid tumor fibromatosis: a multicenter EMSOS study.

BMC Cancer 2021 Apr 20;21(1):437. Epub 2021 Apr 20.

Orthopaedic Oncology Department, Azienda Ospedaliero Universitaria Careggi, Florence, Italy.

Background: Extra-abdominal desmoid tumor fibromatosis (DTF) is a rare, locally aggressive soft tissue tumour. The best treatment modality for this patient cohort is still object of debate.

Questions/purpose: This paper aimed to (1) to compare the outcomes of DTF after different treatment modalities, (2) to assess prognostic factors for recurrence following surgical excision, and (3) to assess prognostic factors for progression during observation.

Methods: This was a retrospective multicenter study under the patronage of the European Musculoskeletal Oncology Society (EMSOS). All seven centres involved were tertiary referral centres for soft tissue tumours. Baseline demographic data was collected for all patients as well as data on the diagnosis, tumour characteristics, clinical features, treatment modalities and whether they had any predisposing factors for DTF.

Results: Three hundred eighty-eight patients (240 female, 140 male) with a mean age of 37.6 (±18.8 SD, range: 3-85) were included in the study. Two hundred fifty-seven patients (66%) underwent surgical excision of ADF, 70 patients (18%) were observed without therapy, the residual patients had different conservative treatments. There were no significant differences in terms of tumour recurrence or progression between the different treatment groups. After surgical excision, younger age, recurrent disease and larger tumour size were risk factors for recurrence, while tumours around the shoulder girdle and painful lesions were at risk of progression in the observational group.

Conclusion: Local recurrence rate after surgery was similar to progression rates under observation. Hence, observation in DTF seems to be justified, considering surgery in case of dimensional progression in 2 consecutive controls (3 and 6 months) and in painful lesions, with particular attention to lesions around the shoulder girdle.
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http://dx.doi.org/10.1186/s12885-021-08189-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059004PMC
April 2021

Custom-Made 3D-Printed Implants as Novel Approach to Reconstructive Surgery after Oncologic Resection in Pediatric Patients.

J Clin Med 2021 Mar 4;10(5). Epub 2021 Mar 4.

Orthopedic Department, University of Pisa, Via Paradisa 2, 56124 Pisa, Italy.

Recently, custom-made 3D-printed prostheses have been introduced for limb salvage surgery in adult patients, but their use has not been described in pediatric patients. A series of 11 pediatric patients (mean age 10.8 years; range 2-13) with skeletal tumors treated with custom-made implants for the reconstruction of bony defects is described. Patients were followed up every 3 months. Functional results were evaluated by the Musculoskeletal Tumor Society Score (MSTS) for upper and lower limbs. The mean follow-up was 25.7 months (range 14-44). Three patients died after a mean of 19.3 months postoperatively-two because of disease progression and the other from a previous malignancy. Three patients experienced complications related to soft tissues. One patient required device removal, debridement, and antibiotic pearls for postoperative infection. Partial osseointegration between grafts and host bone was observed within a mean of 4 months. At the final follow-up, mean MSTS score was 75%. 3D prostheses may yield biological advantages due to possible integration with the host bone and also through the use of vascularized flaps. Further research is warranted.
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http://dx.doi.org/10.3390/jcm10051056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961419PMC
March 2021

Antibacterial hydrogel coating in joint mega-prosthesis: results of a comparative series.

Eur J Orthop Surg Traumatol 2021 Feb 5. Epub 2021 Feb 5.

Department of Orthopaedic Oncology and Reconstructive Surgery, University of Florence, Azienda Ospedaliera Universitaria Careggi, Largo Brambilla, 3, 50134, Florence, Italy.

Purpose: Joint mega-prosthesis after bone tumors, severe trauma or infection is associated with high rates of post-surgical septic complications. A fast-resorbable antibacterial hydrogel coating (DAC®, Defensive Antibacterial Coating) has previously been shown to be able to significantly reduce surgical site infection in various clinical settings. Aim of the present study was to evaluate the safety and efficacy of the DAC hydrogel coating to prevent early periprosthetic joint infection after joint mega-prosthesis.

Methods: In this three-centers, case-control study, 43 patients, treated with an antibacterial hydrogel coated mega-prosthesis for oncological (N = 39) or non-oncological conditions (N = 4), were retrospectively compared with 43 matched controls, treated with mega-implants without the coating. Clinical, laboratory and radiographic examinations were performed to evaluate the occurrence of post-surgical infection, complications and adverse events.

Results: At a mean follow-up of 2 years, no evidence of infection or adverse events were observed in the DAC-treated group, compared to six cases of post-surgical infection in the control group.

Conclusion: This matched case-control study shows that a fast-resorbable, antibiotic-loaded coating can be safely used to protect joint mega-prosthesis, providing a reduction of early surgical site infections with no side effects. Larger prospective trials with longer follow-ups are warranted to confirm this report.

Trial Registration: RS1229/19 (Regina Elena National Cancer Institute Experimental Registry Number).
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http://dx.doi.org/10.1007/s00590-021-02884-7DOI Listing
February 2021

Treatment options in femoral radiation fractures following soft tissue sarcoma: Incidence, risk factors, failures and flowchart of treatment.

Injury 2021 Jun 24;52(6):1597-1605. Epub 2020 Dec 24.

Department of Orthopaedic Oncology and Reconstructive Surgery, Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy.

Introduction: The femur is the most frequent involved site by post-attinic fractures. The appropriate treatment of pathological fractures after radiotherapy is still controversial as they are associated with a high risk of delayed consolidation and non-union. Authors review a single Center series of pathological fractures after radiation therapy in patients affected by soft tissue sarcomas analyzing incidence, risk factors, failure rate and proposing a flow chart of treatment of postattinic fractures of the femur.

Methods: Authors selected 570 patients treated by limb salvage surgery associated to radiation therapy from 1992 to 2018. A pathological fracture during follow up was observed in 28 cases (5%). The mean time between the onset of the fracture after the prior surgery + radiotherapy was 70 months (range 3-182). The mean follow-up from the fracture was 86 months (range 9-222).

Results: The fracture treatment was performed with an intramedullary nail in 15 cases. Eight femoral fractures healed uneventfully (57%) and 6 required further surgical procedures. A total of eight patients underwent prosthetic replacement, 3 as a primary treatment and 5 as a salvage procedure after failure of internal fixation. Five patients developed a deep infection (62.5%).We observed 10 non-union (53%) in 19 patients treated with osteosynthesis. Overall amputation rate of the entire series was 18%. Authors propose a flowchart of treatment for femoral fractures.

Conclusion: Intramedullary nailing is the treatment of choice in postradiation diaphyseal fractures of long bones, prosthetic replacement in meta-epiphyseal fracture site. Free vascularized grafts remain a valid salvage solution after failure of internal fixation.
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http://dx.doi.org/10.1016/j.injury.2020.12.010DOI Listing
June 2021

A hollow, custom-made prosthesis combined with a vascularized flap and bone graft for skeletal reconstruction after bone tumour resection.

Surg Oncol 2021 Mar 29;36:56-60. Epub 2020 Nov 29.

Department of Plastic Surgery and Microsurgery, Azienda Ospedaliero Universitaria Careggi, Florence, Italy. Electronic address:

Purpose: While limb-sparing surgery is now possible for more than 80% of patients with bone tumours, wide resection is often required, necessitating bone reconstruction. This paper aims to present a surgical technique that combines the advantages of a hollow, titanium, custom-made prosthesis and the biological aspects of microsurgical flaps and bone graft.

Patients And Methods: From June 2016 to September 2017 at our institution, six consecutive patients with skeletal tumours underwent one-stage reconstructive surgery with concomitant implantation of a 3D-printed prosthesis.

Results: At an average follow-up of 30 months (range: 18-45), no early complications were observed, and no implant removals were needed. One patient experienced a delayed haematogenous deep infection, which healed after surgical debridement. Three patients died of their underlying disease 18, 22, and 23 months after surgery, respectively. All flaps and custom reconstructions were successful, with primary osseointegration at a mean of four months (range: 2-7). Patients' average Musculoskeletal Tumour Society score was 23.2 (range: 18-28).

Conclusion: A hollow, custom-made, titanium prosthesis filled with bone graft, used in conjunction with a microsurgical flap, may offer good osseointegration in different anatomic locations among a patient population with a high risk of infection, pseudarthrosis, and long-term mechanical complications. The surgical technique's advantages are preliminarily demonstrated. Further studies with longer follow-up periods and larger sample sizes are required to confirm our findings.
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http://dx.doi.org/10.1016/j.suronc.2020.11.014DOI Listing
March 2021

Re-excision after unplanned excision of soft tissue sarcomas: Long-term results.

Surg Oncol 2020 Sep 27;34:212-217. Epub 2020 Apr 27.

Department of Orthopaedic Oncology and Reconstructive Surgery, Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy‬. Electronic address:

Background: Unplanned excisions of soft tissue sarcomas are still not infrequent events with patients presenting to referral Centers after having received an inadequate surgical treatment. In literature, both the wait-and-see policy and the "aggressive" management with a re-excision have been advocated. The purposes of this study were to analyze the incidence of detectable residual tumor in surgical specimens following a re-excision and to verify the long-term results of patients treated with a re-excision after previous unplanned excision.

Methods: We retrospectively evaluated 131 patients affected by localized soft tissue sarcoma (95 high grade; 36 low grade) of the limbs or the superficial trunk treated at our Institution, from 2000 to 2013, with a re-excision after a previous unplanned inadequate excision. Site, size, depth, histotype, grade, adjuvant therapies, time from unplanned surgery to re-excision were recorded and evaluated in association with clinical results. We specifically evaluated the disease-specific survival, local recurrence free survival, distant metastases free survival and the event free survival.

Results: Mean follow-up for living patients was 10.9 years (median 11.2 years), with a follow-up ranging from 14 to 227 months. 34% of patients underwent a re-excision within the first 2 months after unplanned surgery, while 66% of patients at more than 2 months. Residual detectable tumor cells were found on histological examination in 54% of re-excisions. A wide margin was obtained in 123 cases, a persisting positive margin in 8 patients. Disease-specific survival was 93.5%, 91.6% and 89.6% at 5, 10 and 15 years for whole series and 90.9%, 88.2% and 85.7% for high grade tumors. Event-free survival in patients affected by high grade tumors rated 75.0% at 5 years, 72.4% at 10 years and 72.4% at 15 years. Local recurrence free survival in high grade tumors was 87.6%, 86.2% and 86.2% at 5, 10 and 15 years. The grade of the tumor (high grade) and the initial dimension of the tumor (≥5 cm) were associated with worst survival. High grade tumor impacted negatively also on local recurrence free survival and event free survival. Instead, the initial size of the tumor significantly affected the event free survival but not the local recurrence free survival. No significant differences of outcome were found analyzing tumor depth, time interval to re-excision, presence of residual tumor or margins.

Conclusion: Based on our results and literature findings, we believe that surgeons should offer a re-excision procedure in those patients presenting with an inadequate excision of a high grade soft-tissue tumor, in particular with tumors larger than 5 cm before excision. Indeed, if an adequate second treatment is performed with surgery ± radiotherapy, the long-term results of patients receiving a re-excision after unplanned excision of a high grade soft tissue sarcoma seem to be comparable to the results generally reported for wide primary excisions. More debatable is whether to perform a re-excision or not in patients with low-grade tumors. Perhaps, in this latter group a wait and see policy can eventually be offered as well as in high grade tumors when a re-excision procedure could involve major surgery or significantly affect postoperative function.
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http://dx.doi.org/10.1016/j.suronc.2020.04.026DOI Listing
September 2020

Clinical features, prognostic factors and outcome in a series of 29 extra-skeletal Ewing Sarcoma. Adequate margins and surgery-radiotherapy association improve overall survival.

J Orthop 2020 Sep-Oct;21:236-239. Epub 2020 Mar 25.

Divisione di Ortopedia Oncologica e Ricostruttiva Azienda Ospedaliero Universitaria Careggi Firenze, Italy.

Objective: Authors review a series of 29 extra-skeletal Ewing Sarcoma (EES).

Methods: They analyzed characteristics, prognostic factors and outcome of EES.

Results: Authors report 60% Overall Survival (OS) and 56% of Event Free Survival (EFS) at 5 years. Better 5 years EFS was found in patients with localized disease (68.8%) compared to metastatic EES (33.3%) (p = 0.042). Radiotherapy + surgery offered the best local treatment (p=0.017). Volume (p = 0.032), Surgical margins (p = 0.01), metastatic disease (p = 0.0013) were a significant prognostic factor for OS at 5-yrs.

Conclusion: Adequate margins and surgery+radiotherapy improve Overall Survival.
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http://dx.doi.org/10.1016/j.jor.2020.03.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7132112PMC
March 2020

Total femur prosthesis in oncological and not oncological series. Survival and failures.

J Orthop 2020 Jan-Feb;17:215-220. Epub 2019 Nov 12.

Divisione di Ortopedia Oncologica e Ricostruttiva, Azienda Ospedaliero Universitaria Careggi, Firenze, Italy.

Total femur prosthesis (TFP) can be used in both oncological and prosthetic revision surgery. A retrospective analysis of 32 patients receiving a TFP at a single Center between 2002 and 2018 was performed. The average follow-up was 60 months. Revision implant free survival (RIFS) of the implants was 87% at 5 and 10 years and 72% at 15 years. Overall implant survival (OIS) of the prosthesis was 90% at 5, 10 and 15 years. Complications observed: two soft tissue failures, two infection failure and one tumor progression failure.
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http://dx.doi.org/10.1016/j.jor.2019.11.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928329PMC
November 2019

Patterns of Care and Survival in Elderly Patients With Locally Advanced Soft Tissue Sarcoma.

Am J Clin Oncol 2019 10;42(10):749-754

Departments of Biomedical, Experimental, and Clinical Sciences, Radiation Oncology Unit.

Objectives: The aim of this study was to analyze patterns of care in elderly soft tissue sarcoma (STS) patients and their impact on clinical outcome and treatment-related toxicity.

Materials And Methods: We retrospectively collected data of >65-year-old patients diagnosed with locally advanced STS between 1991 and 2017 in a single institution.

Results: The study included 111 patients: 105 (94.6%) patients underwent surgery, associated with preoperative (n=19, 17.1%) or postoperative radiotherapy (n=72, 64.8%). Anthracycline-based chemotherapy was prescribed in 41.4% of patients (n=46). Acute grade ≥3 postoperative radiotherapy-related radiation dermatitis and all grades of chemotherapy-induced neutropenia were significantly correlated to age >80 years (P=0.02) and >70 years (P=0.045), respectively. The mean follow-up was 4.1 years (range, 0.1 to 17.7). Three-year and 5-year local recurrence-free survival were 80.3% and 75.7%, respectively; neither treatment-related nor patient-related characteristics affected local recurrence. Three-year and 5-year distant relapse-free survival were 59.6% and 44.6%, respectively. On multivariate Cox regression, undifferentiated pleomorphic sarcoma histology and Charlson Comorbidity Index >7 were independent factors associated with distant relapse-free survival (P=0.026 and P=0.0001). Overall survival was 62% and 46.6% at 3 and 5 years, respectively. On multivariate Cox regression, surgery and Charlson Comorbidity Index <7 were independent factors associated with overall survival (P=0.006 and P=0.0001).

Conclusions: In this study, elderly STS patients receiving a tailored treatment encompassing surgery, radiotherapy, and/or chemotherapy obtained an improved outcome, although caution is advised because of increased toxicity in relation to age. Comorbidities should be considered to offer the best treatment option to this frail patient population.
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http://dx.doi.org/10.1097/COC.0000000000000594DOI Listing
October 2019

Calcaneal reconstruction after total calcanectomy with iliac crest free flap.

Microsurgery 2019 Nov 22;39(8):704-709. Epub 2019 Mar 22.

Plastic and Reconstructive Microsurgery, Careggi University Hospital, Florence, Italy.

Introduction: Calcaneal tumors being a rare occurrence, surgical options and outcomes are not well-known. Extensive defects following wide resection, especially in weight-bearing areas, still remain a challenge and different reconstructive techniques have been proposed. The aim of this report was to analyze the clinical and functional long-term outcomes of heel reconstruction using an iliac crest free flap.

Patients And Methods: Four patients who underwent calcaneal reconstruction between 1999 and 2012 were included. Two were females and mean age was 27 years, ranging 18-42 years. Each patient underwent total calcanectomy, for two osteoblastomas, one osteosarcoma, and one Ewing's sarcoma. An iliac crest flap was harvested and shaped to fit the residual space. After the articular cartilage at recipient site was debrided, the flap was fixed to the talus and the cuboid.

Results: The average size of the flaps was 2 x 7 x 5 cm. Postoperatively wound dehiscence, screw breaking, and graft fracture healed conservatively. All the arthrodesis healed successfully and no donor site complication occurred. At an average follow-up of 13 years (range 6-19 years) any patient claimed pain, evident limp or limitation of daily activities. Computerized pedobarographic examination and gait analysis revealed a satisfactory result and an acceptable weight-bearing area in the reconstructed limb in each patient.

Conclusions: Calcaneal reconstruction with iliac crest free flap is likely to provide good chances of a long-lasting result, especially in young patients. Particularly, it provides the possibility to adequately shape the graft to fit the bone loss while using the crest as the weight-bearing surface.
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http://dx.doi.org/10.1002/micr.30452DOI Listing
November 2019

Preoperative Denosumab With Curettage and Cryotherapy in Giant Cell Tumor of Bone: Is There an Increased Risk of Local Recurrence?

Clin Orthop Relat Res 2018 09;476(9):1783-1790

G. Scoccianti, F. Totti, M. Scorianz, D. A. Campanacci, Department of Orthopaedic Oncology and Reconstructive Surgery, Azienda Ospedaliero Universitaria Careggi, Firenze, Italy G. Baldi, Department of Medical Oncology, Hospital of Prato, Prato, Italy G. Roselli, Department of Radiology, Azienda Ospedaliero Universitaria Careggi, Firenze, Italy G. Beltrami, Department of Paediatric Orthopaedic Oncology, Azienda Ospedaliero Universitaria Careggi, Firenze, Italy A. Franchi, Department of Translational Research and New Technologies, Department of Anatomic Pathology, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy R. Capanna, Department of Orthopaedics and Traumatology, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.

Background: Denosumab is a monoclonal RANKL antibody, which was originally introduced for the treatment of osteoporosis and bone metastases from solid tumors, but more recently has been used for treatment of giant cell tumor of bone (GCTB). In GCTB, denosumab has been used as a single agent in patients with inoperable tumors; it also has been used before surgery in some patients with the aim to downstage the tumor to facilitate a joint-preserving procedure (curettage) rather than a resection. However, few studies are available evaluating the benefits and risks of denosumab for the latter indication.

Questions/purposes: (1) Does preoperative treatment with denosumab reduce the risk of local recurrence in patients treated for GCTB? (2) Are there adverse effects of short-term denosumab use before surgery and, if so, what are they?

Methods: All patients with a diagnosis of GCTB surgically treated at our institution from June 2009 to June 2016 with curettage and cryotherapy were retrospectively evaluated to compare patients treated with curettage alone versus patients treated with curettage after preoperative therapy with denosumab. During that period, we treated 97 patients for GCTB; 30 patients were excluded because they received a resection; 34 patients were excluded because they received curettage without cryotherapy. Of the remaining 33 patients, four were excluded because they received denosumab only after surgery, one because she received zoledronic acid, one because she received a curettage after her refusal of a resection that was the advised procedure, two because they were lost to followup early, and four because they were treated for recurrence rather than a new diagnosis of GCTB. The remaining 21 patients were included. Twelve lesions had been treated with surgery after denosumab and nine with surgery alone. During the study period, we preferentially used denosumab for the more aggressive-looking lesions. After curettage, cryotherapy of the residual bone walls was performed with argon cryoprobes to -150° C after pouring gel into the cavity, and we then used cement (17 patients) or morcellized allograft (four patients). Tumors were Campanacci Grade 3 in eight of 12 patients in the denosumab group and in two of nine patients in the surgery-only group (p = 0.08), but the extent of epiphyseal juxtaarticular bone involvement was not different between the groups with the numbers available. Median followup was 39 months (range, 14-55 months) in the denosumab group and 27 months (range, 18-92 months) in the surgery-only group. We used chart review to record the proportion of patients in each treatment group who had a local recurrence and to tally adverse events.

Results: With the numbers available, there was no difference in the proportion of patients experiencing a recurrence (five of 12 in the denosumab group and one of nine in the surgery-only group; p = 0.18). We found no adverse effects associated with denosumab either during or after treatment; specifically, we found no alterations in electrolyte levels, blood count, or liver and renal function parameters. In this small series, no patient has developed osteonecrosis of the jaw.

Conclusions: In this small series, use of denosumab before surgery for GCTB appeared to allow the reforming of a bone peripheral rim around the tumor, perhaps facilitating curettage rather than osteoarticular resection in some patients. However, we did not observe a decrease in the risk of local recurrence with the use of denosumab, suggesting that it may not decrease the aggressiveness of the disease; according to our preliminary results, we cannot exclude that the rate of local recurrence could be even higher after curettage in denosumab-treated patients than in nontreated patients, and until or unless larger studies demonstrate such a reduction, primary intralesional surgery without denosumab seems more prudent when curettage is feasible at presentation. We did not observe any adverse effects with denosumab, but we caution readers that this study was underpowered to detect even relatively common complications and relatively large differences in the risk of local recurrence. Future studies should evaluate denosumab prospectively; given the relative rarity of this tumor, we suspect multicenter studies are needed to achieve this.

Level Of Evidence: Level III, therapeutic study.
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http://dx.doi.org/10.1007/s11999.0000000000000104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6259811PMC
September 2018

Influence of age and subtype in outcome of operable liposarcoma.

Radiol Med 2019 Apr 12;124(4):290-300. Epub 2018 Nov 12.

Department of Radiation Oncology, Azienda Ospedaliero Universitaria Careggi, University of Florence, Largo Brambilla 3, 50141, Florence, Italy.

Aim: Liposarcoma (LPS) is rare tumor deriving from adipocytes. LPS is classified into histological subtypes: well-differentiated (WDLPS), dedifferentiated (DDLPS), myxoid (MLPS) and pleomorphic (PLPS). A tailored approach taking into account the specificity of disease subtype and age at presentation could be helpful in delineating therapeutic management of liposarcoma. In this paper, we report a retrospective series of a single-institution cohort of patients with LPS, undergoing surgery and radiotherapy and/or chemotherapy. The aim of this study is to evaluate whether clinical characteristics, tumor- and treatment-related features affect clinical outcome in patients treated with curative intent for non-metastatic liposarcoma.

Methods: Data of patients with locally advanced, non-metastatic liposarcoma treated between 1990 and 2015 were retrospectively reviewed. Data about patient, tumor and treatment features were collected. Two patients subgroups were identified according to age (cutoff: age < 65 years or > 65 years). Statistical analysis was performed to assess correlation between the above-cited variables and local recurrence-free survival (DFS-LR), distant metastasis-free survival, overall survival (OS) and disease-specific survival (DSS); moreover, differences in clinical outcome between the two age groups were identified.

Results: Data of 186 patients were collected. At diagnosis, 27.4% of patients were 65 years or older. At a median follow-up of 8.6 years (range 0.1-27.3 years), Kaplan-Meier (KM) survival analysis showed that LR, DM, OS and DSS were 75.5%, 76.6%, 48.1% and 72.1%, respectively. KM analysis showed that age > 65, DDLPS and lower limb localization were related to LR (p = 0.001, p = 0.0001 and p = 0.0001, respectively). Association between LR, age and DDLPS persisted both at univariate (p = 0.003 and p = 0.0001, respectively) and multivariate Cox regression (CR) analysis (p = 0.024 and p = 0.002). Age, tumor depth and grading influenced distant recurrence, both at KM (p = 0.023, p = 0.026 and p = 0.016) and univariate CR (p = 0.026, p = 0.042 and p = 0.012). Age and grading were confirmed at multivariate analysis (p = 0.009 and p = 0.017). Patients with WDLPS and wide excision had significantly better OS (p = 0.001 and p = 0.03, respectively), while histological G3 and age > 65 were related with worse OS (p = 0.008 and p = 0.0001, respectively). Age, DDLPS and grade were related to OS at univariate (p = 0.0001, p = 0.0001 and p = 0.03, respectively) and multivariate CR analysis (p = 0.031, p = 0.0001 and p = 0.001, respectively). However, analyzing the specific causes of death, female died less often for tumor-related causes, with a DSS of 91.0% compared to 57.4% of male counterpart (p = 0.005). At Kaplan-Meier analysis, postoperative radiotherapy resulted in a statistically significant better disease-specific survival than postoperative radiotherapy (82.9% vs. 46.2%, p = 0.045). High grade correlated with poorer disease-specific survival (59.3%) than intermediate and low grade (73.4% and 91.6%, respectively) (p = 0.008). Association between DSS, sex and grade persisted both at univariate (p = 0.008 and p = 0.022, respectively) and multivariate Cox regression (CR) analysis (p = 0.014 and p = 0.038). Histotype-driven schedules of treatment should be developed to take into account biological heterogeneity of this disease. Further studies are needed to stratify patients subgroup and develop tailored treatment strategies (i.e., altered fractionations and different chemotherapy regimens in aggressive subtypes), in particular more prospective trials are needed to develop treatment guidelines in elderly STS, taking into account the frailty and the peculiarity of this subgroup.
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http://dx.doi.org/10.1007/s11547-018-0958-4DOI Listing
April 2019

Latissimus dorsi rotational flap combined with a custom-made scapular prosthesis after oncological surgical resection: a report of two patients.

BMC Cancer 2018 Oct 20;18(1):1003. Epub 2018 Oct 20.

Department of Plastic Surgery and Microsurgery, Azienda Ospedaliero Universitaria Careggi, Florence, Italy.

Background: Sarcomas that arise from the scapula or periscapular soft tissues often require a total scapulectomy. This often implies a large complex tissue defect that needs adequate reconstruction of both bone and soft tissue. Although various methods have been developed, no optimal procedure has emerged. Postoperative complications are common and functional recovery is not always satisfactory. This study aims to present a new surgical technique that combines a custom-made scapular prosthesis with a functional latissimus dorsi flap.

Case Presentation: Two patients diagnosed with malignant tumour of the scapular region were surgically treated after proper multidisciplinary evaluation. The first patient underwent the procedure as a first surgery, the second as revision surgery. The new technique comprises three surgical stages: excisional surgery with soft tissue resection and scapulectomy, bone reconstruction with custom-made prosthesis, and soft tissue reconstruction using a latissimus dorsi rotational flap overturned on the prosthesis. The goal is to set up a new functional unit combining an anatomically shaped implant (manufactured using latest three-dimensional printing technology) and a muscular flap, and to maintain the neurovascular supply. The patients were followed up to evaluate functional outcome and complications. Both patients were alive with no evidence of disease. Functional results were satisfactory and the Musculoskeletal Tumor Society scores were 87% and 63%, respectively. No surgical complications such as implant breakage, joint collapse, wound dehiscence, or infection were observed.

Conclusions: This new technique upgrades the role of the latissimus dorsi flap to a functional tool in combination with an anatomical, three-dimensionally printed, custom-made prosthesis, and provides adequate well-vascularized and healthy tissue to maximize the likelihood of successful limb salvage.
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http://dx.doi.org/10.1186/s12885-018-4883-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196007PMC
October 2018

A matched cohort study of radio-chemotherapy versus radiotherapy alone in soft tissue sarcoma patients.

Radiol Med 2019 Apr 12;124(4):301-308. Epub 2018 Sep 12.

Department of Radiation Oncology, Azienda Ospedaliero Universitaria Careggi, University of Florence, Largo Brambilla 3, 50141, Florence, Italy.

Purpose: Adjuvant radiotherapy is the standard postoperative treatment after conservative surgery in high risk soft tissue sarcoma. The role of adjuvant chemotherapy is still debated. Therefore, a matched cohort analysis was performed in high risk soft tissue patients to analyse differences in terms of clinical outcome and toxicity between patients treated with concomitant radio-chemotherapy (RTCT) and radiotherapy (RT) alone.

Materials And Methods: For each patient in RT group was selected a patient in the RTCT group matching for age, T stage and grading. Acute and late toxicity were recorded, overall survival, recurrence free survival and distant metastases free survival were analysed and compared between the two groups.

Results: Ninety patients were selected, half of patients underwent radio-chemotherapy and half received radiotherapy alone. During the treatment Grade 3 dermatitis was recorded in 15 (16.7%) patients, 6 (6.7%) patients associated chemotherapy and during follow up 12 (13.3%) patients developed grade 2 late fibrosis, 3 (3.3%) joint stiffness and 1 (1.1%) patient experienced a bone fracture. There were no differences in the rate of acute and late toxicity between RTCT and RT alone group. Nineteen (21.1%) patients developed local recurrence, overall 5-year local relapse free survival was 83%. There were no differences between the two groups. 29 patients developed distant metastases, 14 (15.6%) patients in the RTCT group and 15 (16.7%) patients in the RT group. The 5-year distant metastases free survival was 67%. Age > 65 years was the only independent factor affecting distant recurrence (HR = 5.7, 95% CI 2.7-11.9; p = 0.001). At the time of analysis 15 (16.7%) patients were dead, 6 (6.7%) patients in the RTCT group and 9 (10%) patients in the RT group. 5-years overall survival was: 88%. At multivariate analysis age > 65 years was an independent prognostic factor of overall survival (HR = 3.7, 95% CI 1.2-12.1, p = 0.037).

Conclusions: Prospective randomized studies with large size population and with subgroup analysis for histological subtypes are necessary to clarify the role of adjuvant chemotherapy in soft tissue sarcoma patients. Tailored treatment has to be considered in elderly soft tissue patients to guarantee a better outcome in this high risk and fragile population.
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http://dx.doi.org/10.1007/s11547-018-0939-7DOI Listing
April 2019

Surgical Treatment of Sacral Chordoma: En Bloc Resection with Negative Margins is a Determinant of the Long-Term Outcome.

Surg Technol Int 2018 Nov;33:343-348

Department of Orthopedic Surgery, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.

Study Design: Retrospective case series.

Objective: To report the outcome of a series of patients with sacral chordoma who were surgically treated at a single center.

Summary: Chordomas are low-grade malignant tumors that arise from remnants of the notochord. They are most often found in the sacrum, spine and skull-base. These tumors have a slow clinical evolution and may eventually metastasize, even after adequate treatment. Rarely, they can dedifferentiate into high-grade sarcomas. Traditionally, chordomas were considered to be resistant to chemotherapy and standard radiation therapy. However, recently, adrotherapy has been shown to be effective for local and systemic control of the disease. In this study, clinical outcomes and local and systemic recurrence were reviewed to identify prognostic factors for local and systemic control.

Methods: Thirty-three patients with sacral chordoma (19 males, 14 females; median age 61 y, range 43-80) who were surgically treated at our institution between 1994 and 2015 were reviewed. In 24 patients, resection was performed above S2. No patients received pre-operative radiotherapy (RT). Three cases received RT (carbon ion therapy) as treatment for local recurrence. Wide (R0) surgical margins were achieved in 17 patients, marginal (R1) margins in 14 patients and intralesional (R2) margins in 2 patients.

Results: At a median follow-up of 53 months (range 0-198), 19 patients were continuously disease-free, 6 were disease-free after local recurrence (5) or metastases (1), 3 were alive with disease (2 local recurrence and 1 metastasis), 4 were dead of disease (1 patient died intraoperatively) and 1 was dead of another cause. Local recurrence was observed in 9 cases (27%); all 9 were treated surgically and 3 received carbon ion therapy after surgical intralesional excision. Overall survival at 10 years was 86.6%. Local recurrence-free survival at 10 years was 51%. A statistical analysis confirmed the importance of negative surgical margins (R0) to achieve local control of the disease (p = 0.0007). High resections (above S2) were associated with lower survival and higher risk of local recurrence.

Conclusion: Surgical en bloc resection is the primary treatment for sacral chordoma. Carbon ion therapy is used when it is difficult to obtain wide surgical margins. Due to morbidity and the disabling sequelae of surgery, adrotherapy may be considered an alternative to high (above S2-S3) sacral chordoma resections.
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November 2018

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

Is an Intramedullary Nail a Valid Treatment for Limb-Length Discrepancy After Bone Tumor Resection? Case Descriptions.

Surg Technol Int 2018 Nov;33:281-288

Department of Orthopaedic Oncology and Reconstructive Surgery, University of Florence, Azienda Ospedaliera Universitaria Careggi, Florence, Italy.

One of the most frequent outcomes after resection of bone tumors in children is a limb-length discrepancy. An intramedullary nail is a valid method for lengthening the limb. We report our experience with four cases of limb-length discrepancy in the lower limbs several years after the primary treatment of bone tumor resection and subsequent reconstruction. Two femoral PRECICE® nails (NuVasive, Inc., San Diego, CA) were introduced retrograde and two were introduced in an anterograde manner. All four cases healed and showed a reduction of the limb-length discrepancy, early loading, and complete bone osteogenesis. In one case, a reduction of the joint ROM recovered after release of the iliotibial band and a quadriceps release according to Judet's arthrolysis.
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November 2018

Liposarcoma: Clinico-pathological analysis, prognostic factors and survival in a series of 307 patients treated at a single institution.

J Orthop Sci 2018 Nov 11;23(6):1038-1044. Epub 2018 Jul 11.

Azienda Ospedaliera Universitaria Careggi Firenze, Ortopedia Oncologica e Ricostruttiva, Firenze, Italy.

Background And Objectives: Liposarcoma (LPS) is a malignant mesenchymal tumor and the most common soft tissue sarcoma. Four different subtypes are described: well differentiated (WD) LPS or atypical lipomatous tumor (ALT), dedifferentiated (DD) LPS, myxoid LPS, and pleomorphic LPS (PLS). The objective of the study was to investigate prognostic factors and clinical outcome of liposarcoma.

Methods: We retrospectively examined the clinico-pathological features of a series of 307 patients affected by Liposarcoma at a mean follow-up of 69 months (range 6-257). ALT/WD LPS were analyzed separately. The influence of site, size, type of presentation, grading, histotype and local recurrence on local and systemic control and survival was assessed.

Results: The statistical analysis indicated that only surgical margins represented a significant prognostic factor for local recurrence in ALT/WD LPS (P = 0.0007) and other subtypes of LPS (P = 0.0055). In myxoid, PLS and DD LPS, significant prognostic factors for metastasis free survival (MFS) were surgical margins (P = 0.0009), size of the tumor (P = 0.0358), histology (P = 0.0117) and local recurrence (P = 0.0015). In multivariate analysis, surgical margins (0.0180), size (0.0432) and local recurrence (0.0288) correlated independently with MFS. Margins (P = 0.0315), local recurrence (P = 0.0482) and metastases (P < 0.0001) were prognostic factors for overall survival (OS).

Conclusion: Marginal surgery can be an accepted treatment for ALT/WD LPS. In other liposarcoma subtypes (Myxoid, DD, PLS) wide or radical surgery is recommended as the margins significantly influence local recurrence-free survival (LRFS), metastasis-free survival (MFS) and overall survival (OS). Local recurrence and metastases were significant prognostic factors for OS.
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http://dx.doi.org/10.1016/j.jos.2018.06.008DOI Listing
November 2018

Allograft Reconstruction of the Extensor Mechanism after Resection of Soft Tissue Sarcoma.

Adv Orthop 2018 22;2018:6275861. Epub 2018 May 22.

Department of Orthopedic Surgery, Azienda Ospedaliero-Universitaria Pisana, Via Paradisa 2, Cisanello, 56125 Pisa, Italy.

Introduction: Soft tissue tumors around the knee joint still pose problems for the excision and subsequent reconstruction.

Methods: In the 6 included patients the soft tissue sarcoma has its base on the anterior surface of the extensor mechanism and expands towards the skin. The entire extensor apparatus (quadriceps tendon, patella, and patellar tendon) was resected and replaced by a fresh-frozen allograft.

Results: The mean follow-up was 6.7 years (range: 2-12.4 years). In two patients a local recurrence occurred, resulting in a 5-year local recurrence-free rate of 66.7% (95% CI: 19.5%-90.4%). Distant metastases were found in 4 patients resulting in a 5-year metastasis-free rate of 33.3% (95% CI: 4.6%-67.5%). Two patients underwent at least one revision surgery, including one patient in whom the allograft had to be removed. According to the ISOLS function score 24.7 points (range: 19-28 points) were achieved at the last follow-up. The mean active flexion of the knee joint was 82.5° (range: 25-120°) and a mean extension lag of 10° (range: 0-30°) was observed.

Conclusions: The replacement of the extensor mechanism by an allograft is a reasonable option, allowing wide margins and restoration of active extension in most patients.

Trial Registration: The presented study is listed on the ISRCTN registry with trial number ISRCTN63060594.
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http://dx.doi.org/10.1155/2018/6275861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987318PMC
May 2018

Biological Intercalary Reconstruction with Bone Grafts After Joint-Sparing Resection of the Lower Limb: Is this an Effective and Durable Solution for Joint Preservation?

Surg Technol Int 2018 06;32:346-345

Department of Orthopaedic Oncology and Reconstructive Surgery University of Florence, Azienda Ospedaliera, Universitaria Careggi, Florence, Italy.

Due to advances in neoadjuvant therapies and preoperative imaging modalities, joint-sparing resections have become appealing in bone tumor surgery. However, the intercalary reconstruction of metadiaphyseal bone defects of the femur and the tibia after juxta-articular tumor resection remains challenging. Both biological and prosthetic reconstructions have been used for joint-sparing resections, but little is known about the long-term outcome of these procedures. The authors reviewed a consecutive series of 64 patients treated with joint-sparing intercalary resection and reconstruction with bone grafts. Inclusion criteria were an osteotomy line within 5 cm from the knee and ankle joint surface and an osteotomy line proximal to 1 cm below the lesser trochanter at the hip level. Intra-epiphyseal resection was performed in 25 patients (39%)and intercalary resection was performed in 39 (61%). Reconstruction included 49 allograft + vascularized fibular graft (VFG), 10 allografts, and 5 VFG + structural allogenic grafts. At a mean follow-up of 117 months (range 12-305), 51 patients (80%) were continuously disease-free, and 6 showed no evidence of disease after treatment of local recurrence or metastatic lesion. One patient was alive with lung metastases at 26 months of follow-up and six patients died of disease. In the entire series of 64 patients, 26 had a non-oncological complication that required surgical revision (40.6%). Overall survival (OS) of reconstruction was 92% at 5 years and 90% at 10 and 15 years. Limb salvage survival (LSS) was 94% at 5, 10 and 15 years. Twenty-two fractures occurred in 17 patients (26.5%). There were a total of nine non-unions (14%). Six patients (9.3%) presented early wound dehiscence (average 1.8 months, range 0-6). A deep infection occurred in 3 cases (4.7 %). In 12 patients treated with VGF reconstruction (12/54:22%), a donor-site complication was observed. The overall Musculoskeletal Tumor Society (MSTS) functional score in 54 evaluable patients, who were alive with reconstruction in situ, was 27 points (range 18-30). Biologic intercalary reconstructions with bone grafts resulted in effective joint-sparing resections of the lower limb, allowing joint preservation in all but one case who required a total knee replacement for varus osteoarthritis. Despite the high rate of complications requiring surgical revision, at 15 years, overall survival of the reconstruction was 90% and limb salvage survival was 94%. In our experience, revision-free survival was better with VFG reconstruction than with allograft alone and the combination of VFG and allogenic graft seems to favor spontaneous fracture-healing and to decrease the non-union rate.
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June 2018

Safety of concurrent adjuvant radiotherapy and chemotherapy for locally advanced soft tissue sarcoma.

Tumori 2018 Oct 11;104(5):322-329. Epub 2018 Apr 11.

1 Department of Radiation-Oncology, Azienda Ospedaliero Universitaria Careggi, University of Florence, Florence, Italy.

Introduction:: This retrospective study analyzes the safety and feasibility of concurrent chemoradiotherapy (CRT) in adjuvant treatment of soft tissue sarcoma (STS).

Methods:: A total of 158 patients with STS were retrospectively analyzed. Anthracycline-based computed tomography was performed in high-risk patients. Acute radiotherapy toxicity and chemotherapy-related toxicity were assessed according to the Common Terminology Criteria for Adverse Events 4.0; late radiotherapy toxicity was recorded according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria.

Results:: Fifty-four (34.2%) patients received CRT. Mean follow up was 5.4 years (range .2-21.1 years). Local DFS-recurrence-free survival, distant DFS-relapse-free survival, and overall survival were 79.1%, 76.4%, and 64.6%, respectively, at last follow-up. Leukopenia occurred in 11.4% of patients. Skin acute toxicity developed in 60.1% of patients and determined interruption of radiotherapy treatment in 19 (12%) patients. Nineteen patients (12%) experienced moderate fibrosis (grade 2). Mild and moderate joint stiffness was recorded in 16 (10.1%) patients. Size ≥5 cm was the only predictor of local recurrence at multivariate analysis (hazard ratio [HR] 9.65, 95% confidence interval [CI] 1.28-72.83, p = .028). Age and stage resulted as independent distant relapse predictors (HR 4.77, 95% CI 1.81-12.58, p = .002 and HR 4.83, CI 1.41-16.57, p = .012, respectively). At Cox regression univariate analysis, Karnofsky Performance Status, size, and stage were significant survival predictors (HR 2.23, 95% CI 1.02-4.87, p = .045; HR 2.88, 95% CI 1.10-7.52, p = .031; HR 2.59, 95% CI 1.11-6.04, p = .028).

Conclusions:: Concurrent CRT is a well-tolerated treatment option with no additional toxicity compared to exclusive radiotherapy or sequential CRT.
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http://dx.doi.org/10.1177/0300891618765565DOI Listing
October 2018

Denosumab treatment of inoperable or locally advanced giant cell tumor of bone - Multicenter analysis outside clinical trial.

Eur J Surg Oncol 2018 09 31;44(9):1384-1390. Epub 2018 Mar 31.

The Royal Orthopaedic Hospital NHS Foundation Trust, Birmingham, UK.

Background: Giant cell tumor of bone (GCTB) is an osteolytic, locally aggressive, rarely metastazing bone tumor. This is a retrospective study evaluating a large series of GCTB patients treated with denosumab in routine practice in 6 European reference centers.

Methods: Patients with locally advanced, unresectable or metastatic GCTB, treated with denosumab outside clinical trials were eligible. Primary end-point was progression-free survival (PFS) for all patients; secondary end-points were: type of surgery, relapse rate and event-free survival for patients after preoperative denosumab + surgery.

Results: We identified 138 patients treated in the period 2011-2016. In 40/43 cases the diagnosis was confirmed by H3F3A gene mutation. Median follow-up time was 23 months (range 6-48). Primary tumor was located in lower limb (38%) - mostly in femur and tibia, in upper limb (34%), and in pelvis/axial skeleton/ribs (28%). 110 (80%) patients had primary tumors, 28 (22%) recurrent tumors after previous surgical procedures (+/- radiotherapy). 89/138 patients had locally advanced GCTB and underwent neoadjuvant denosumab. The median denosumab treatment duration was 8 months (median number of cycles 11), 98% had clinical benefit from therapy. 39 (44%) had wide en-bloc resection - WE (+implantation of the prosthesis in 17 cases), the other 50 (56%) cases had intralesional curettage - C. Progression after surgical treatment was observed in 19 patients, 16 of them after C (32%); 13 patients underwent denosumab re-challenge, and all responded. Two-year progression-free survival (PFS; from denosumab start) rate was 81%; 2-year EventFS (from surgery) was significantly better in WE group (93%) vs 55% in C group (p = 0.006). Treatment was well tolerated with only 2 cases of grade 3 toxicity and one osteonecrosis of the jaw.

Conclusion: Our retrospective study confirms that denosumab is extremely efficient in unresectable/metastatic disease as well as in a neoadjuvant setting. Our data confirm excellent efficacy and short-term tolerability of this drug. Our data suggest that neoadjuvant therapy with denosumab is the option for treatment of initially locally advanced tumors to facilitate complete surgical resection or avoid mutilating surgery. The risk of recurrences after curettage of GCTB following denosumab raises questions about the optimal management of such cases.
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http://dx.doi.org/10.1016/j.ejso.2018.03.020DOI Listing
September 2018

Soft tissue sarcomas: new opportunity of treatment with PARP inhibitors?

Radiol Med 2019 Apr 26;124(4):282-289. Epub 2018 Mar 26.

Department of Biomedical, Experimental and Clinical Sciences "Mario Serio", Section of Radiation Oncology, University of Florence, Largo Brambilla 3, 50134, Florence, Italy.

Background: Poly(ADP-ribose) polymerases (PARP) are a large family of enzymes involved in several cellular processes, including DNA single-strand break repair via the base-excision repair pathway. PARP inhibitors exert antitumor activity by both catalytic PARP inhibition and PARP-DNA trapping, moreover PARP inhibition represents a potential synthetic lethal approach against cancers with specific DNA-repair defects. Soft tissue sarcoma (STSs) are a heterogeneous group of mesenchymal tumors with locally destructive growth, high risk of recurrence and distant metastasis.

Objectives: The purpuse of this review is to provide an overview of the main preclinical and clinical data on use of PARPi in STSs and of effect and safety of combination of PARPi with irradiation.

Results: Due to numerous genomic alterations in STSs, the DNA damage response pathway can offer an interesting target for biologic therapy. Preclinical and clinical studies showed promising results, with the most robust evidences of PARPi efficacy obtained on Ewing sarcoma bearing EWS-FLI1 or EWS-ERG genomic fusions. The activity of PARP inhibitors resulted potentiated by chemotherapy and radiation. Although mechanisms of synergisms are not completely known, combination of radiation therapy and PARP inhibitors exerts antitumor effect by accumulation of unrepaired DNA damage, arrest in G2/M, activity both on oxic and hypoxic cells, reoxygenation by effect on vessels and promotion of senescence. Early trials have shown a good tolerance profile.

Conclusions: The use of PARP inhibitors in advanced stage STSs, alone or combined in multimodal treatments, is of great interest and warrants further investigations.
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http://dx.doi.org/10.1007/s11547-018-0877-4DOI Listing
April 2019

Giant schwannoma of the foot: a case report and literature review.

Clin Cases Miner Bone Metab 2017 May-Aug;14(2):265-268. Epub 2017 Oct 25.

Department of Orthopaedic and Trauma Surgery, University of Pisa, Pisa, Italy.

A schwannoma is a rare, benign tumor originating from Schwann cells of peripheral nerve sheath. It commonly occurs in subjects between 20 and 50 years of age, and its malignant transformation is exceptional. While schwannomas usually affect the head and neck region, localization in the lower extremity is exceptionally rare, and even fewer cases have described schwannomas occurring in the foot. We report a case of a giant schwannoma of the foot diagnosed in a 65-year-old woman. A giant schwannoma of the foot is an extremely rare soft tissue tumor. MRI may allow an earlier diagnosis and provide valuable information about the size and possible bone invasion. This case report noted that a complete excision of the schwannoma may prevent the risk of local recurrence, regardless of its size.
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http://dx.doi.org/10.11138/ccmbm/2017.14.2.265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5726225PMC
October 2017

Modular Endoprostheses for Nonneoplastic Conditions: Midterm Complications and Survival.

Biomed Res Int 2016 5;2016:2606521. Epub 2016 Dec 5.

Department of Orthopaedic and Trauma Surgery, University of Pisa, Pisa, Italy.

The use of modular endoprostheses is a viable option to manage both tumor resection and severe bone loss due to nonneoplastic conditions such as fracture sequelae, failed osteoarticular grafts, arthroplasty revisions, and periprosthetic fractures. We sought to investigate both midterm complications and failures occurred in 87 patients who underwent a megaprosthetic reconstruction in a nonneoplastic setting. After a mean follow-up of 58 (1-167) months, overall failure-free survival was 91.5% at 1 year, 80% at 2 years, 71.6% at 5 years, and 69.1% at 5 and 10 years. There was no significant difference in the survival rate according to the diagnosis at the index procedure ( = 0.921), nor to the reconstruction site ( = 0.402). The use of megaprostheses in a postneoplastic setting did not affect survival rate in comparison with endoprosthetic reconstruction of pure nonneoplastic conditions ( = 0.851). Perimegaprosthetic infection was the leading complication, occurring in 10 (11.5%) patients and implying a megaprosthetic revision in all but one case. Physicians should consider these results when discussing with patients desired outcomes of endoprosthetic reconstructions of a nonneoplastic disease.
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http://dx.doi.org/10.1155/2016/2606521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5165145PMC
February 2017

Hereditary Multiple Exostoses: a review of clinical appearance and metabolic pattern.

Clin Cases Miner Bone Metab 2016 May-Aug;13(2):110-118. Epub 2016 Oct 5.

Department of Orthopaedic Oncology and Reconstructive Surgery, "Azienda Ospedaliera Universitaria Careggi", Firenze, Italy.

Hereditary multiple exostoses (HME) is an inherited genetic condition characterized by the presence of multiple exostoses (osteochondromas). MHE is a relatively rare autosomal dominant disorder, mainly caused by loss of function mutations in two genes: exostosin-1 (EXT1) and exostosin-2 (EXT2). These genes are linked to heparan sulfate (HS) synthesis, but the specific molecular mechanism leading to the disruption of the cartilage structure and the consequent exostoses formation is still not resolved. The aim of this paper is to encounter the main aspects of HME reviewing the literature, in order to improve clinical features and evolution, and the metabolic-pathogenetic mechanisms underlying. Although MHE may be asymptomatic, a wide spectrum of clinical manifestations is found in paediatric patients with this disorder. Pain is experienced by the majority of patients, even restricted motion of the joint is often encountered. Sometimes exostoses can interfere with normal development of the growth plate, giving rise to limb deformities, low stature and scoliosis. Other many neurovascular and associated disorders can lead to surgery. The most feared complication is the malignant transformation of an existing osteochondroma into a secondary peripheral chondrosarcoma, during adulthood. The therapeutic approach to HME is substantially surgical, whereas the medical one is still at an experimental level. In conclusion, HME is a complex disease where the paediatrician, the geneticist and the orthopaedic surgeon play an interchangeable role in diagnosis, research and therapy. We are waiting for new studies able to explain better the role of HS in signal transduction, because it plays a role in other bone and cartilage diseases (in particular malignant degeneration) as well as in skeletal embryology.
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http://dx.doi.org/10.11138/ccmbm/2016.13.2.110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5119707PMC
October 2016

Risks and benefits of combining denosumab and surgery in giant cell tumor of bone-a case series.

World J Surg Oncol 2016 Nov 4;14(1):281. Epub 2016 Nov 4.

Department of Orthopedic Oncology, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, 50134, Firenze, Italy.

Background: The RANK ligand inhibitor denosumab is being investigated for treatment of giant cell tumor of bone, but the available data in the literature remains sparse and controversial. This study analyzes the results of combining denosumab with surgical treatment and highlights possible changes for the oncologic surgeon in daily practice.

Methods: A total of 91 patients were treated surgically for giant cell tumor of bone between 2010 and 2014 in an institution, whereas 25 patients of the total additionally received denosumab and were part of this study. The average age of the patients was 35 years. Eleven patients received denosumab pre- and postoperatively, whereas with 14 patients, the denosumab treatment was applied either before (7 patients) or after (7 patients) the surgery. The average preoperative therapy duration was 3.9 months and the postoperative therapy 6 months by default.

Results: Sixteen patients presented a large tumor extension necessitating a resection of the involved bone or joint. In 10 of these patients, the indication for a resection procedure was abandoned due to the preoperative denosumab treatment and a curettage was performed. In the remaining six cases, the surgical indication was not changed despite the denosumab treatment, and two of them needed a joint replacement after the tumor resection. Also with patients treated with curettage, denosumab seems to facilitate the procedure as a new peripheral bone rim around the tumor was built, though a histologic analysis reveals viable tumor cells persisting in the denosumab-induced bone formation. After an average follow-up of 23 months, one histologically proven local recurrence occurred, necessitating a second curettage. A second patient showed a lesion in the postoperative imaging highly suspicious for local relapse which remained stable under further denosumab treatment. No adverse effect of the denosumab medication was observed in this study.

Conclusions: Denosumab can be a help to the oncologic surgeon by reconstituting a peripheral rim and switching the stage from aggressive to active or latent disease. But as tumor cells remain in the new-formed bone, the surgical technique of curettage has to be changed from gentle to more aggressive to avoid higher local recurrence rates.
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http://dx.doi.org/10.1186/s12957-016-1034-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095954PMC
November 2016
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