Multidisciplinary management of adolescents and young adults (AYA) sarcoma: A successful effort of an adult high-volume cancer center.

INTRODUCTION: The aim of this retrospective study was to investigate the clinicopathological characteristics of AYA sarcomas and their clinical outcomes at a high-volume single center. METHODS: Demographic, clinicopathological data on the diagnosis, treatment and follow-up of all sarcoma patients aged 16-39 years (ys) observed at our Institute between January 2010 and December 2021 were retrospectively collected, including diagnostic (TTD) and treatment delay(TTT), clinical outcomes (OS and PFS), and late-treatment effects. RESULTS: We identified 228 AYA patients, median age 30 years, 29% ≤ 25 years, 57% males, 88% soft tissue sarcomas (STS), and 12% bone sarcomas (BS). Among STSs, 13% were small round cell tumors (SRCT), 52% intermediate-high-grade, 24% low-grade STSs. Among BS, 32% were high-grade. Median TTD and TTT were 120 (0-8255) and 7 days (0-83), respectively. Surgery was performed in 83%, radiotherapy in 29%, and systemic therapy in 27%. Median follow-up was 72.9 months(1.6-145), 5-year and 10-year OS were 78.5% and 62%, respectively. Kaplan-Meyer analysis showed a significantly better 5-year OS and PFS for patients with >92 days of TTD (OS 85.7% vs. 66.7%, p = 0.001, PFS 50.2% vs. 24.9%, p = 0.009). According to age (≤25 years vs. > 25 years), 5-year OS was 69.8% versus 82.2%, respectively (p = 0.047). CONCLUSION: Our analysis confirmed previous data on sarcoma AYA patients followed in a referral center. Unexpectedly, diagnostic delay was not associated with poor OS and PFS. Patients <25 years showed a poorer prognosis due to the higher incidence of SRCT.

Secondary osteosarcoma: a challenge indeed.

BACKGROUND: The risk of survivors developing a secondary bone sarcoma after being treated for pediatric cancers is well established. The aim of this study was to examine the clinical characteristics and outcomes of patients with secondary osteosarcoma (SOS). METHODS: The study concerns survivors of childhood and adolescence primary neoplasms (PN) treated with chemotherapy, with or without radiotherapy and surgery, subsequently diagnosed with SOS. RESULTS: We identified 26 patients (13 females, 13 males) who developed SOS a median 7.3 years after being diagnosed with a PN (5/7 of these patients tested for Li-Fraumeni and found positive for the syndrome). The sample's median age was 8.0 and 15.0 years when their PN and SOS were diagnosed, respectively. To treat their PN, 24 out of 26 patients had been given radiotherapy, and 19 had received chemotherapy including doxorubicin. A considerable number of SOS occurred at unfavorable sites (nine hip bone, six skull). All but one patient received chemotherapy with tailored schedules, omitting doxorubicin in 19 cases. Eighteen of the 26 patients underwent surgery. The 5- and 10-year overall survival and probabilities after the diagnosis of SOS (95% confidence interval) were 50% (32.7-76.5%) and 38.9% (22.4-67.4%); 5- and 10-year progression-free survival was 47% (29.9-73.7%) and 35.2% (19.3-64.4%), respectively. CONCLUSIONS: The survival rates after SOS are lower than in patients with primary osteosarcoma, but not negligible. It is therefore mandatory to discuss the best choice of treatment for such patients at a referral center, in terms of their chances of cure and quality of life.

Pelvic ring reconstruction with double-barreled fibular free flap: A systematic review.

INTRODUCTION: Pelvic ring reconstruction after internal hemipelvectomy is an extremely challenging surgical procedure, and mandatory reconstruction is to provide a durable and pain-free functional outcome, especially for young, active patients. One of the most widely employed techniques is reconstruction with a double-barreled fibular free flap (DBF). The aim of our work was an in-depth analysis of the outcome of pelvic ring reconstruction performed using the above-mentioned method, in particular looking for a correlation between the fixation technique and either ambulation status or complications. MATERIALS AND METHODS: A systematic review was performed in November 2020 using PubMed and MedLine Ovid databases according to the PRISMA guidelines and the results were statistically analyzed. RESULTS: Studies were published between 1994 and 2015. A DBF was used in each case, with a total of 30 patients. Reconstruction was performed with screws in 13 cases, Cotrel-Dubousset rod fixation in 6, screws and plate in 5, screws with external fixation in 4, and ISOLA in 2. Follow-up time ranged from 3 to 131 months. Functional outcome was excellent in 4 patients and good in 26 patients. Statistical analysis showed no statistical evidence of existing correlation between fixation technique and complications (p = .873), while statistical correlation between age and fixation technique was found (p < .001). CONCLUSION: Reconstruction of pelvic ring with DBF provides an overall good functional outcome. Our data indicate that there is no statistical evidence of existing correlation between the fixation technique and either complications or ambulation status.

What is the best clinical approach to recurrent/refractory osteosarcoma?

Introduction: Osteosarcoma is the most common malignant bone tumor. It is currently treated with pre-and postoperative chemotherapy, associated with surgical resection of the tumor.Area covered: Relapses occur in about one in three patients presenting with localized disease, and three in four of those with metastases at diagnosis. Relapsing disease carries a very poor prognosis, with 5-year survival rates ranging between 13% and 40%.Expert opinion: Patients with unilateral lung involvement or solitary lung metastases and a recurrence-free interval (RFI) longer than 24 months have a better prognosis, and could be managed with surgical resection and close observation. Complete surgical resection of all sites of disease remains essential to survival: patients unable to achieve complete remission have a catastrophic overall survival rate. The role of second-line chemotherapy is not at all clear, and no controlled studies are available on this topic. It is worth considering for patients unable to achieve complete surgical remission, and those with multiple metastases and/or a RFI <24 months. Given their dismal prognosis, patients with multiple sites of disease not amenable to complete surgical resection should also be considered for innovative therapeutic approaches.

Fibulo-scapho-lunate fusion after resection of the distal radius: Case series, review of the literature and critical analysis of bone fixation.

Fibulo-scapho-lunate fusion is a technique that allows residual movement in the wrist in case of wide bone resection replacing the distal radius by a vascularised fibular transfer. Some authors have used this technique with favourable results but the distal synthesis seems to not be standardised at all, many different osteosynthesis methods have been proposed. This paper reports a complete review of the present day literature about this subject and, evaluating the different proposed osteosynthesis techniques referred in literature, suggests a standardization of the synthesis methods with dorsal plating. We report some technical considerations and results of three cases operated with a stable dorsal osteosynthesis (twice with a double plate and once with a long plate). We evaluate the time of healing and the clinical result.

Extensor hallucis longus tendon and soft-tissue reconstruction with palmaris longus tendon included in a radial forearm free flap: A case report.

Reconstruction of foot structures is challenging because of the need to restore both anatomy and function. Extensor hallucis longus (EHL) excision without reconstruction could result in a flexion deformity of the toe at the interphalangeal joint. In this report, we present a case of the use of a palmaris longus tendon included in a fasciocutaneous radial forearm free flap to reconstruct EHL tendon and soft tissues of the distal foot dorsum. A 41-year-old woman presented with a recurrence of myxoinflammatory fibroblastic sarcoma on the medial part of the left foot dorsum. The EHL tendon was sacrificed, leaving a soft-tissue defect of 14 × 5 cm and 14-cm tendon gap. A 14 × 5 cm radial forearm flap with a 16-cm section of palmaris longus tendon was harvested from the left forearm. Radial artery and its comitant vein were anastomosed with dorsalis pedis artery and vein. EHL tendon repair was performed from the composite mass to the proximal and distal stumps. No complication in the postoperative period occurred. At latest follow-up, 12 months postoperatively, the patient showed a normal joint function and was satisfied with the treatment. Palmaris longus tendon included in a radial forearm free flap could be recommended for combined soft tissue and tendon defects, particularly on the foot dorsum.

Calcaneal reconstruction after total calcanectomy with iliac crest free flap.

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.

Primary metastatic osteosarcoma: results of a prospective study in children given chemotherapy and interleukin-2.

To improve the poor prognosis for children with metastatic osteosarcoma (OS), interleukin-2 (IL-2) was added to the standard treatment due to its capacity to activate lymphocytes and differentiate lymphocyte subsets into lymphokine-activated killer (LAK) cells that are capable of recognizing and killing various tumor cells. This study concerns a cohort of unselected patients aged < 18 years with metastatic OS, who were treated with IL-2, high-dose methotrexate, doxorubicin, cisplatin, ifosfamide, LAK reinfusion, and surgery, between 1995 and 2010. Thirty-five patients aged 4-17 years were involved. Thirty-two of the 35 patients underwent surgery on their primary tumor, and 25 had surgery on lung metastases too. Twenty-seven patients received IL-2 plus LAK reinfusion. The median follow-up was 130 months (77-228), and the 3-year event-free and overall survival rates were 34.3 and 45.0%, respectively. Eleven patients remained alive, all of whom achieved a complete surgical removal of the primary tumor and lung metastases (1 patient did not receive lung resections due to complete lung metastases remission). Patients who had a complete surgical remission of the primary and metastatic sites and who responded well to chemotherapy had a better event-free survival. These results confirm the importance of complete surgical remission and point to a noteworthy (though still be ameliorate) survival rate in our series of patients, underling a potential role for immunotherapy with IL-2 and LAK/NK cell activation.

Efficacy of trabectedin in advanced soft tissue sarcoma: beyond lipo- and leiomyosarcoma.

OBJECTIVE: Trabectedin is effective in leiomyosarcoma and liposarcoma, especially the myxoid variant, related to the presence of the FUS-CHOP transcript. We evaluated the efficacy of trabectedin in specific subgroups of patients with soft tissue sarcomas (STS). METHODS: Seventy-two patients with advanced anthracycline-pretreated STS, who received trabectedin at a dose of 1.5 mg/m(2) every 3 weeks by continuous 24-hour infusion, were retrospectively analyzed. Best response rate according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria and severe adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.02) were evaluated. Secondary endpoints included progression-free survival and overall survival (OS). RESULTS: Median age was 48 (range, 20-75) years, with a median Eastern Cooperative Oncology Group performance status of 0. The median number of previous chemotherapy regimens was 1 (range, 0-5). Median number of trabectedin cycles was 3 (range, 1-17). About 69/72 patients (95.8%) were evaluable for response: 9 patients (13%) achieved partial response and 26 (37.7%) stable disease. According to histotype, clinical benefit (partial response + stable disease) was reported in synovial sarcoma (n=5), retroperitoneal liposarcoma (n=10), myxoid liposarcoma (n=5), leiomyosarcoma (n=8), high-grade undifferentiated pleomorphic sarcoma (n=5), Ewing/peripheral primitive neuroectodermal tumor (n=1), and malignant peripheral nerve sheath tumor (n=1). Any grade AEs were noncumulative, reversible, and manageable. G3/G4 AEs included anemia (n=1, 1.4%), neutropenia (n=7, 9.6%), liver toxicity (n=6, 8.3%), and fatigue (n=2, 2.8%). With a median follow-up time of 11 (range, 2-23) months, median progression-free survival and OS of the entire cohort were 2.97 months and 16.5 months, respectively. CONCLUSION: Our experience confirms trabectedin as an effective therapeutic option for metastatic lipo- and leiomyosarcoma and suggests promise in synovial sarcomas and high-grade undifferentiated pleomorphic sarcoma.

[Rehabilitation pathway after knee arthroplasty with mega prosthesis in osteosarcoma]. / Il percorso riabilitativo del paziente sottoposto a intervento di protesi da grandi resezioni di ginocchio per neoplasia scheletrica.

INTRODUCTION: The knee is the most frequent location for osteosarcoma (60%). Until 30 years ago patients with osteosarcoma were treated with an amputation of the affected limb; today 85% of these cases are treated with a "Limb Salvage" procedure, through replacement of the affected bone with a mega prosthesis implant. AIM: To measure functional recovery of patients with a knee mega-prosthesis and how rehabilitation impacts on quality of life (QOL); another aim is to define rehabilitation guidelines to manage these patients in the rehabilitation pathway. METHODS: A sample of outpatients with knee mega-prosthesis were selected in the follow-up orthopedic oncology surgery between march and may 2013. We measured the functional outcome using the multidimensional standardized Musculoskeletal Tumor Society scale (MSTS) that gives a score (0-5) for each of 7 items: pain, range of motion, stability, deformity, strength, functional activity, emotional acceptance. RESULTS: The sample included 28 outpatients. The median MSTS score was 29 (min 19, max 33) equal to 83%. Only 14 patients (50%) followed a correct rehabilitation path after surgery. DISCUSSION: 21 cases got "excellent" outcomes and 3 "good" (based on MSTS classification). In few cases (n 4) the outcome was "fairly good", related to necessity of a prosthesis surgical revision based on instability of implant (because of usage). Quadricep strength is the item that most affects the final score. There is a statistically significant correlation between high scores and patients who have recently undergone surgery. We found higher scores in patients that followed a physiotherapy program after surgery: the difference was statistically significant. CONCLUSIONS: Mega-prosthesis implants give satisfactory functional outcomes. These outcomes keep high score in time. It is recommended to follow the guidelines described in the purposed rehabilitation program.

Atypical lipomatous tumors: should they be treated like other sarcoma or not? Surgical consideration from a bi-institutional experience.

BACKGROUND: To identify the best surgical approach to atypical lipomatous tumors we reviewed 171 patients who underwent surgery at two sarcoma referral centers with different surgical policies. METHODS: Of the 151 patients (88 %) with primary tumors, 95 were treated at Institution A and 76 were treated at Institution B. At Institution A, a wide surgical resection, including a slight cuff of soft tissue around the mass, was adopted, which was defined as marginal resection (MR) according to the Enneking classification. At Institution B, a simple tumor resection (SR), according to the Enneking classification, was employed. En bloc surgical resection was the goal in both centers. The primary outcomes of the study were local recurrence-free survival (LRFS), incidence of secondary dedifferentiation at recurrence, and presence of residual tumor after re-excision. RESULTS: Sixteen patients (9 %) had local recurrence. The 10-year LRFS was 82 %. No cases of secondary dedifferentiation were observed. Residual tumor after re-excision was found in 46 % of cases. In univariate analysis, sclerosing subtype, tumor rupture, and SR were unfavorable prognostic factors for LRFS. Sclerosing subtype and tumor rupture were independent prognostic factors for LRFS in multivariate analysis. SR was significantly associated with tumor rupture. CONCLUSIONS: Sclerosing subtype and tumor rupture are unfavorable prognostic factors for local recurrence. MR is associated with a lower risk of tumor rupture than SR. Neurovascular and major muscle resections are not necessary in principle. Re-excision after unplanned surgery is not always mandatory. A preoperative core needle biopsy could be useful in identifying the sclerosing subtype.