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Background/Objective: Surgical treatment of aneurysmal bone cysts (ABCs) can be challenging, especially in the spine. Non-surgical treatments such as with denosumab have shown promising results in different osteolytic pathologies. This retrospective observational study aimed to evaluate the long-term clinical and radiologic response of patients with ABCs of the mobile spine treated with denosumab and propose an updated treatment algorithm. Methods: Six patients with relapsed and symptomatic ABCs of the mobile spine were treated with denosumab (120 mg subcutaneously on days 1, 8, 15, 29, and every 4 weeks thereafter) between 2012 and 2023. Disease assessments were conducted using CT and MRI at 3, 6, 9, and 12 months post-treatment. Clinical data, including pain levels, symptoms, and adverse events, were documented from patients' charts. Results: Patients underwent an initial phase of treatment with denosumab, receiving a mean of 22 administrations (range 13-42) over a median follow-up period of 41 months (range 15-98 months). Clinical improvement was observed in all patients after 4 weeks of treatment, and all patients demonstrated a radiological response after 12-24 weeks on denosumab. Three patients were progression-free after discontinuing denosumab following 13, 15, and 42 administrations, respectively. At the last follow-up, after 38, 43, and 98 months, these patients remained stable without relapse of the disease. Three patients had a relapse of disease after denosumab; two of them underwent denosumab re-challenge, while one patient received one mesenchymal stem cells (MSCs) injection. All patients showed clinical and radiological improvement and were resulted to be disease-free at the last follow-up. Conclusions: This study demonstrates the long-term efficacy and safety of denosumab in treating ABCs of the mobile spine, as well as the potential of re-challenge in managing recurrence. A treatment algorithm is proposed, positioning denosumab as a viable therapeutic option after other local treatments. Careful patient selection, monitoring, and further research are necessary to optimize denosumab use for ABCs.
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Musculoskeletal sarcomas pose major challenges to researchers and clinicians due to their rarity and heterogeneity. Xenografting human cells or tumor fragments in rodents is a mainstay for the generation of cancer models and for the preclinical trial of novel drugs. Lately, though, technical, intrinsic and ethical concerns together with stricter regulations have significantly curbed the employment of murine patient-derived xenografts (mPDX). In alternatives to murine PDXs, researchers have focused on embryonal systems such as chorioallantoic membrane (CAM) and zebrafish embryos. These systems are time- and cost-effective hosts for tumor fragments and near-patient cells. The CAM of the chick embryo represents a unique vascularized environment to host xenografts with high engraftment rates, allowing for ease of visualization and molecular detection of metastatic cells. Thanks to the transparency of the larvae, zebrafish allow for the tracking of tumor development and metastatization, enabling high-throughput drug screening. This review will focus on xenograft models of musculoskeletal sarcomas to highlight the intrinsic and technically distinctive features of the different hosts, and how they can be exploited to elucidate biological mechanisms beneath the different phases of the tumor's natural history and in drug development. Ultimately, the review suggests the combination of different models as an advantageous approach to boost basic and translational research.
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BACKGROUND: Neurotrophic tyrosine receptor kinase (NTRK) gene-fusion targeted molecules revolutionized the paradigm of treatment of a limited subgroup of cancers of various histologies. Entrectinib and larotrectinib obtained unprecedented response rates in patients with cancer harboring NTRK rearrangements. This evidence recently led to the agnostic approval of these drugs, and evidence (confirmation) of their activity in a broader disease setting is emerging. Here, we report the case of a patient affected by EML4-NTRK3 rearranged undifferentiated spindle cell bone sarcoma treated with larotrectinib, and we argue (discuss about) the incidence and clinical presentation of NTRK gene-fusion positive bone sarcomas, the potential use of upfront treatment with NTRK inhibitors in neoadjuvant setting, and the role of a multidisciplinary tumor board. Despite the rarity of these rearrangements in patients with primitive bone sarcomas, the therapy with NTRK inhibitors represents a highly effective strategy to be pursued in selected cases even in neoadjuvant settings. The management of these very rare cancers should always be discussed in a multidisciplinary board of reference centers.
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PURPOSE: The purpose of this study was to analyze the imaging features of extraskeletal osteosarcomas (ESOS) on computed tomography (CT) and magnetic resonance imaging (MRI) and to investigate their associations with overall survival (OS) using uni- and multivariable survival analyses. MATERIALS AND METHODS: This two-center retrospective study included all consecutive adult patients between 2008 and 2021 with histopathologically-proven ESOS who underwent pre-treatment CT and/or MRI. Clinical and histological characteristics, ESOS presentation on CT and MRI, treatment and outcomes were reported. Survival analyses were performed using Kaplan-Meier analysis and Cox regressions. Associations between imaging features and OS were searched using uni- and multivariable analyses. RESULTS: Fifty-four patients were included (30/54 [56%] men, median age: 67.5 years). Twenty-four died of ESOS (median OS: 18 months). ESOS were mostly deep-seated (46/54, 85%) in the lower limb (27/54, 50%) with a median size of 95 mm (interquartile range: 64, 142; range: 21-289 mm). Mineralization was seen on 26/42 (62%) patients, mainly gross-amorphous (18/26; 69%). ESOS were generally highly heterogeneous on T2-weighted images (38/48; 79%) and contrast-enhanced (CE) T1-weighted images (29/40; 72%), with necrosis (39/40; 97%), well-defined or focally infiltrative margins (39/47; 83%), with moderate peritumoral edema (39/47; 83%) and rim-like peripheral enhancement (17/40; 42%). Size, location, mineralization on CT, signal intensity heterogeneity on T1-, T2- and CE-T1-weighted images and hemorragic signal on MRI were associated with poorer OS (range of log-rank P = 0.0069-0.0485). At multivariable analysis, hemorragic signal and signal intensity heterogeneity on T2-weighted images remained predictive for poorer OS (hazard ratio [HR] = 2.68, P = 0.0299; HR = 9.85, P = 0.0262, respectively) CONCLUSION: ESOS typically presents as mineralized heterogeneous and necrotic soft tissue tumor with a possible rim-like enhancement and limited peritumoral abnormalities. MRI may help estimate outcome of patients with ESOS.
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Neoplasias Óseas , Osteosarcoma , Neoplasias de los Tejidos Blandos , Adulto , Masculino , Humanos , Anciano , Femenino , Estudios Retrospectivos , Osteosarcoma/diagnóstico por imagen , Osteosarcoma/terapia , Neoplasias de los Tejidos Blandos/patología , Tomografía Computarizada por Rayos X , Imagen por Resonancia Magnética/métodos , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/terapiaRESUMEN
BACKGROUND: Undifferentiated small round cell sarcomas (URCSs) represent a diagnostic challenge, and their optimal treatment is unknown. We aimed to define the clinical characteristics, treatment, and outcome of URCS patients. METHODS: URCS patients treated from 1983 to 2019 at 21 worldwide sarcoma reference centres were retrospectively identified. Based on molecular assessment, cases were classified as follows: (1) CIC-rearranged round cell sarcomas, (2) BCOR::CCNB3-rearranged round cell sarcomas, (3) unclassified URCSs. Treatment, prognostic factors and outcome were reviewed. RESULTS: In total, 148 patients were identified [88/148 (60%) CIC-rearranged sarcoma (median age 32 years, range 7-78), 33/148 (22%) BCOR::CCNB3-rearranged (median age 17 years, range 5-91), and 27/148 (18%) unclassified URCSs (median age 37 years, range 4-70)]. One hundred-one (68.2%) cases presented with localised disease; 47 (31.8%) had metastases at diagnosis. Male prevalence, younger age, bone primary site, and a low rate of synchronous metastases were observed in BCOR::CCNB3-rearranged cases. Local treatment was surgery in 67/148 (45%) patients, and surgery + radiotherapy in 52/148 (35%). Chemotherapy was given to 122/148 (82%) patients. At a 42.7-month median follow-up, the 3-year overall survival (OS) was 92.2% (95% CI 71.5-98.0) in BCOR::CCNB3 patients, 39.6% (95% CI 27.7-51.3) in CIC-rearranged sarcomas, and 78.7% in unclassified URCSs (95% CI 56.1-90.6; p < 0.0001). CONCLUSIONS: This study is the largest conducted in URCS and confirms major differences in outcomes between URCS subtypes. A full molecular assessment should be undertaken when a diagnosis of URCS is suspected. Prospective studies are needed to better define the optimal treatment strategy in each URCS subtype.
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Sarcoma de Células Pequeñas , Sarcoma , Neoplasias de los Tejidos Blandos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Biomarcadores de Tumor/genética , Ciclina B , Proteínas de Fusión Oncogénica , Proteínas Proto-Oncogénicas/genética , Proteínas Represoras/genética , Estudios Retrospectivos , Sarcoma/genética , Sarcoma/terapia , Sarcoma/patología , Sarcoma de Células Pequeñas/genética , Sarcoma de Células Pequeñas/terapia , Sarcoma de Células Pequeñas/diagnóstico , Neoplasias de los Tejidos Blandos/patologíaRESUMEN
Background: Giant cell tumors of bone (GCTB) are osteolytic tumors. Denosumab, a RANK-L inhibitor, is approved for GCTB. Data on serum bone turnover marker (sBTM) changes are lacking. We present a phase II correlative study on sBTMs in GCTB patients treated with denosumab. Methods: All GCTB patients receiving denosumab within a multicentre, open-label, phase 2 study were enrolled. Serum levels of carboxyterminal-crosslinked-telopeptide of type I collagen (s-CTX), alkaline phosphatase (ALP), bone-alkaline phosphatase (bALP), parathyroid hormone (sPTH), and osteocalcin (OCN) were prospectively assessed (baseline, T0, 3 months, T1, 6 months, T2). The primary endpoint was assessment of sBTM changes after denosumab; the secondary endpoints were disease-free survival (DFS) and sBTM correlation. Results: In 54 cases, sBTMs decreased during denosumab treatment except for sPTH. With a median follow-up of 59 months, 3-year DFS was 65% (%CI 52−79), with a significantly worse outcome for patients with high (≥500 UI/mL) s-CTX at baseline, as compared to low s-CTX (<500 UI/mL) (3-year DFS for high CTX 45% (95%CI 23−67) vs. 75% (95%CI 59−91) for low s-CTX. Higher median ALP and s-CTX were found for patients with tumor size ≥ 5 cm (p = 0.0512; p = 0.0589). Conclusion: Denosumab induces ALP/OCN and s-CTX reduction. High baseline s-CTX identifies a group of patients at higher risk of progression of the disease.
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BACKGROUND: According to retrospective osteosarcoma series, ABCB1/P-glycoprotein (Pgp) overexpression predicts for poor outcomes. A prospective trial to assess a risk-adapted treatment strategy using mifamurtide in Pgp+ patients was performed. METHODS: This was a phase 2, multicenter, uncontrolled trial including patients 40 years old or younger with nonmetastatic extremity high-grade osteosarcoma stratified according to Pgp expression. All patients received high-dose methotrexate, doxorubicin, and cisplatin (MAP) preoperatively. In Pgp+ patients, mifamurtide was added postoperatively and combined with MAP for a good histologic response (necrosis ≥ 90%; good responders [GRs]) or with high-dose ifosfamide (HDIFO) at 3 g/m2 /d on days 1 to 5 for a histologic response < 90% (poor responders [PRs]). Pgp- patients received MAP postoperatively. After an amendment, the cumulative dose of methotrexate was increased from 60 to 120 g/m2 (from 5 to 10 courses). The primary end point was event-free survival (EFS). A postamendment analysis was performed. RESULTS: In all, 279 patients were recruited, and 194 were included in the postamendment analysis: 70 (36%) were Pgp-, and 124 (64%) were Pgp+. The median follow-up was 51 months. For Pgp+ patients, 5-year EFS after definitive surgery (null hypothesis, 40%) was 69.8% (90% confidence interval [CI], 62.2%-76.2%): 59.8% in PRs and 83.7% in GRs. For Pgp- patients, the 5-year EFS rate was 66.4% (90% CI, 55.6%-75.1%). CONCLUSIONS: This study showed that adjuvant mifamurtide, combined with HDIFO for a poor response to induction chemotherapy, could improve EFS in Pgp+ patients. Overall, the outcomes compared favorably with previous series. Mifamurtide and HDIFO as salvage chemotherapy are worth further study.
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Neoplasias Óseas , Osteosarcoma , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Subfamilia B de Transportador de Casetes de Unión a ATP/uso terapéutico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/patología , Neoplasias Óseas/cirugía , Niño , Supervivencia sin Enfermedad , Extremidades/patología , Humanos , Ifosfamida , Italia , Metotrexato , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Osteosarcoma/cirugía , Estudios Prospectivos , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
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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Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Osteosarcoma/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/etiología , Neoplasias Óseas/mortalidad , Terapia Combinada , Fluorodesoxiglucosa F18 , Perfilación de la Expresión Génica , Humanos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Metástasis de la Neoplasia , Estadificación de Neoplasias , Osteosarcoma/diagnóstico , Osteosarcoma/etiología , Osteosarcoma/mortalidad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Resultado del TratamientoRESUMEN
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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Fibromatosis Agresiva , Tratamiento Conservador , Fibromatosis Agresiva/cirugía , Humanos , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/terapia , Radioterapia Adyuvante , Estudios RetrospectivosRESUMEN
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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Fibrosarcoma , Neoplasias de los Tejidos Blandos , Adulto , Anciano , Anciano de 80 o más Años , Fibrosarcoma/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/diagnóstico por imagen , Pronóstico , Estudios RetrospectivosRESUMEN
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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Conservadores de la Densidad Ósea/uso terapéutico , Denosumab/uso terapéutico , Adolescente , Conservadores de la Densidad Ósea/farmacología , Condroblastoma , Denosumab/farmacología , Humanos , Neoplasias Pulmonares , Masculino , Metástasis de la NeoplasiaRESUMEN
Background: The evidence on high-dose ifosfamide (HD-IFO) use in patients with relapsed osteosarcoma is limited. We performed a retrospective study to analyze HD-IFO activity. Methods: Patients with osteosarcoma relapsed after standard treatment [methotrexate, doxorubicin, cisplatin +/- ifosfamide (MAP+/-I)] with measurable disease according to RECIST1.1 were eligible to ifosfamide (3 g/m2/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. Results: 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, p = 0.034) and CR2 (HR 0.126, p < 0.001) showed a significant correlation with PFS and OS, respectively. No significant correlation was found between outcomes and PARP1 or gene mutations. Conclusions: HD-IFO should be considered as the standard first-line treatment option in relapsed osteosarcoma and control arm of future trial in this setting.
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Neoplasias Óseas/tratamiento farmacológico , Ifosfamida/administración & dosificación , Recurrencia Local de Neoplasia/tratamiento farmacológico , Osteosarcoma/tratamiento farmacológico , Adolescente , Adulto , Anciano , Neoplasias Óseas/cirugía , Niño , Cisplatino/administración & dosificación , Relación Dosis-Respuesta a Droga , Doxorrubicina/administración & dosificación , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Mutación , Poli(ADP-Ribosa) Polimerasa-1/genética , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
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 Viscum album fermentatum Pini (an extract derived from the parasitic plant Viscum album L., European mistletoe) as maintenance therapy in patients with metastatic osteosarcoma in complete surgical remission after the second relapse. The primary endpoint was the PRDFS rate at 12 months (compared to the historical control rate). This is a long-term updated result. Patients and Methods. 10 patients received oral etoposide 50 mg/m2 daily for 21 days every 28 days for 6 months, and 9 patients received Viscum album fermentatum Pini 3 times/wk subcutaneously for 1 year. The study closed early in July 2011 due to insufficient recruitment. Lymphocyte subpopulations were analyzed at T0, T3, T6, T9, and T12 months. RESULTS: On 30 June 2019, at a median follow-up ITT of 83 months (range 3-144 ms), a median PRDFS of 106 ms (2-144) was observed in the Viscum arm with 5/9 patients who never relapse vs a PRDFS of 7 months (3-134) in the etoposide arm (all patients in the Etoposide arm relapsed) (hazard ratio HR = 0.287, 95% CI: 0.076-0.884, p=0.03). Model forecast 10-yr overall survival rates as 64% in the Viscum arm and 33% in the etoposide arm. Lymphocyte subpopulation counts (CD3, CD4, and CD56) showed an increase in the Viscum arm while a decrease was observed in the etoposide arm during treatment. CONCLUSIONS: After 12 years from the start of the trial, the patients in the Viscum arm continue to show a considerably longer PRDFS compared to oral etoposide, and a trend for an advantage in OS is evident even if the number of treated patients is too small to draw conclusions. Viscum as maintenance treatment after complete surgical remission in relapsed osteosarcoma should be further investigated and compared with other drugs.
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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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Antineoplásicos/uso terapéutico , Furanos/uso terapéutico , Cetonas/uso terapéutico , Liposarcoma/diagnóstico , Liposarcoma/tratamiento farmacológico , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Biomarcadores , Femenino , Furanos/administración & dosificación , Furanos/efectos adversos , Humanos , Cetonas/administración & dosificación , Cetonas/efectos adversos , Liposarcoma/complicaciones , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Retratamiento , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
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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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/mortalidad , Terapia Neoadyuvante/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Osteosarcoma/mortalidad , Adolescente , Adulto , Anciano , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/patología , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
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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Neoplasias de la Médula Ósea/secundario , Médula Ósea/patología , Neoplasias Óseas/secundario , Neoplasias Pulmonares/secundario , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Sarcoma de Ewing/patología , Adolescente , Adulto , Médula Ósea/cirugía , Neoplasias de la Médula Ósea/diagnóstico por imagen , Neoplasias de la Médula Ósea/cirugía , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/cirugía , Niño , Preescolar , Femenino , Estudios de Seguimiento , Enfermedades del Pie , Humanos , Lactante , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/cirugía , Masculino , Pronóstico , Estudios Retrospectivos , Sarcoma de Ewing/diagnóstico por imagen , Sarcoma de Ewing/cirugía , Adulto JovenAsunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Osteosarcoma/tratamiento farmacológico , Pirimidinas/uso terapéutico , Sulfonamidas/uso terapéutico , Adolescente , Adulto , Anciano , Neoplasias Óseas/mortalidad , Niño , Femenino , Humanos , Indazoles , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Osteosarcoma/mortalidad , Supervivencia sin Progresión , Terapia Recuperativa/métodos , Adulto JovenRESUMEN
PURPOSE: Osteosarcoma (OS) is the most common primary bone tumor. Despite complete surgical removal and intensive chemotherapeutic treatment, 30%-35% of patients with OS have local or systemic recurrence. Some patients survive multiple recurrences, but overall survival after OS recurrence is poor. This analysis aims to describe and identify factors influencing post-relapse survival (PRS) after a second OS relapse. METHODS: This is a retrospective analysis of 60 patients with a second relapse of OS of the extremities in 2 Italian centers between 2003 and 2013. RESULTS: Treatment for first and subsequent relapses was planned according to institutional guidelines. After complete surgical remission (CSR) following the first recurrence, patients experienced a second OS relapse with a median disease-free interval (DFI) of 6 months. Lung disease was prevalent: 44 patients (76%) had pulmonary metastases. Survival after the second relapse was 22% at 5 years. Lung disease only correlated with better survival at 5 years (33.6%) compared with other sites of recurrence (5%; p = 0.008). Patients with a single pulmonary lesion had a better 5-year second PRS (42%; p = 0.02). Patients who achieved a second CSR had a 5-year second PRS of 33.4%. Chemotherapy (p<0.001) benefited patients without a third CSR. CONCLUSIONS: This analysis confirms the importance of an aggressive, repeated surgical approach. Lung metastases only, the number of lesions, DFI and CSR influenced survival. It also confirms the importance of chemotherapy in patients in whom surgical treatment is not feasible.
Asunto(s)
Neoplasias Óseas/mortalidad , Neoplasias Óseas/patología , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Osteosarcoma/mortalidad , Osteosarcoma/patología , Adolescente , Adulto , Niño , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
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.
Asunto(s)
Quistes Óseos Aneurismáticos/tratamiento farmacológico , Conservadores de la Densidad Ósea/uso terapéutico , Denosumab/uso terapéutico , Adolescente , Adulto , Quistes Óseos Aneurismáticos/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
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.