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BACKGROUND: We report on a series of consecutive patients with localized radiation-associated angiosarcoma (RAAS) of the breast region (BR) treated at two Italian sarcoma reference centers. MATERIALS AND METHODS: We retrospectively reviewed all cases of primary, localized, resectable RAAS of the BR, treated at one of the two participating institutions from 2000 to 2019. Relapse-free survival (RFS) and overall survival (OS) were calculated. The prognostic role of several variables was investigated. A propensity score matched (PSM) analysis was carried out. RESULTS: Eighty-four patients were retrospectively identified. Nineteen out of 84 patients (22.6%) were pretreated with an anthracycline-based regimen for previous cancer. All patients but one underwent surgery, with 37/84 (44.1%) receiving surgery alone and 46/84 (54.8%) a multimodal approach: 18/84 (21.4%) received radiation therapy (RT) and 46/84 (54.9%) received chemotherapy. An anthracycline-based regimen was used in 10/84 patients (11.9%), while a gemcitabine-based regimen was used in 33/84 (39.3%). With a median follow-up of 51 months (interquartile range: 30-126 months), 36/84 patients (42.9%) relapsed and 35/84 patients (41.7%) died (8/84, 9.5% in the lack of metastatic disease). Five-year OS and 5-year RFS were 57% [95% confidence interval (CI) 43% to 68%] and 52% (95% CI 39% to 63%), respectively. Both (neo)adjuvant RT and chemotherapy were associated with better RFS [hazard ratio (HR) 0.25, 95% CI 0.08-0.83; HR 0.45, 95% CI 0.23-0.89] with a trend towards a better OS (HR 0.51, 95% CI 0.18-1.46; HR 0.60, 95% CI 0.29-1.24). Gemcitabine-based regimens seemed to perform better (HR 4.28, 95% CI 1.29-14.14). PSM analysis retained the above results. CONCLUSIONS: This retrospective study supports the use of (neo)adjuvant RT and chemotherapy, in primary, localized resectable RAAS of the BR. An effort to prospectively validate the role of (neo)adjuvant RT and chemotherapy is warranted.
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Neoplasias de la Mama , Hemangiosarcoma , Neoplasias Inducidas por Radiación , Humanos , Hemangiosarcoma/etiología , Hemangiosarcoma/terapia , Hemangiosarcoma/tratamiento farmacológico , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/terapia , Neoplasias de la Mama/patología , Anciano , Neoplasias Inducidas por Radiación/etiología , Adulto , Resultado del Tratamiento , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Retroperitoneal sarcoma (RPS) is a rare tumour that can reach exceptionally large size at diagnosis and affects body weight with its volume. We investigated the risk of nutritional status misclassification based on the Global Leadership Initiative on Malnutrition (GLIM) criteria in RPS patients. METHODS: We retrospectively analyzed the baseline data of patients with primary RPS including anthropometry, Malnutrition Universal Screening Tool (MUST) score and skeletal muscle index (SMI) calculated on preoperative CT scan. Phenotypic GLIM criteria considered were non-volitional weight loss, low-BMI and low muscle mass. MUST score, being inclusive of weight loss, was chosen as its surrogate. Reduced muscle mass was defined with SMI cut-offs <38.5-52.4 cm2/m2 for female and male respectively. RESULTS: From 2018 to 2020, 100 consecutive patients (male/female: 48/52) were included. Median age was 61 (48-68) years, median BMI 24.6 (21.5-27.4) kg/m2. Seven patients (7%) reported MUST score ≥2 and 80 (80%) score 0. Five patients (5%) were underweight, 44 (44%) overweight and obese. Sixty patients (60%) presented low SMI, of those 56 (93%) were normal or overweight, and 46 (77%) not at nutritional risk according to the MUST score. Both underweight BMI and MUST score ≥2 were not correlated with low SMI (p = 0.406, p = 0.612, respectively). No relevant discrepancy was found in the postoperative course of patients with low or normal muscle mass, although SMI was able to better characterize nutritional risk in the proportion of patents with high-grade liposarcoma and predicted worst overall survival. CONCLUSION: GLIM criteria are a useful tool for diagnosis of malnutrition. However, our analysis suggests that phenotypic criteria are not interchangeable with each other. An altered body composition is often hidden in patients with retroperitoneal sarcoma and the use of weight-based classification does not seem to be appropriate, enhancing the role of mass muscle measurement to prevent misdetections of malnourished patient.
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Desnutrición , Sarcoma , Índice de Masa Corporal , Femenino , Humanos , Masculino , Desnutrición/complicaciones , Desnutrición/diagnóstico , Persona de Mediana Edad , Músculo Esquelético , Sobrepeso/complicaciones , Estudios Retrospectivos , Sarcoma/complicaciones , Sarcoma/diagnóstico , Delgadez , Pérdida de PesoAsunto(s)
Neoplasias Gastrointestinales , Tumores del Estroma Gastrointestinal , Sarcoma , Estudios de Seguimiento , Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/epidemiología , Neoplasias Gastrointestinales/terapia , Tumores del Estroma Gastrointestinal/diagnóstico , Tumores del Estroma Gastrointestinal/epidemiología , Tumores del Estroma Gastrointestinal/terapia , Humanos , Sarcoma/terapiaRESUMEN
Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication.
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Hemangioendotelioma Epitelioide , Sarcoma , Adulto , Niño , Consenso , Hemangioendotelioma Epitelioide/diagnóstico , Hemangioendotelioma Epitelioide/tratamiento farmacológico , Humanos , Oncología Médica , Defensa del Paciente , Sarcoma/diagnóstico , Sarcoma/tratamiento farmacológicoRESUMEN
BACKGROUND: This multicentric, retrospective study conducted within the Italian Rare Cancer Network describes clinical features and explores their possible prognostic relevance in patients with advanced epithelioid haemangioendothelioma (EHE) started on surveillance. PATIENTS AND METHODS: We collected data on adult patients with molecularly confirmed, advanced EHE consecutively referred at five sarcoma reference centres between January 2010 and June 2018, with no evidence of progressive disease (PD) and started on surveillance. Overall survival (OS) and progression-free survival (PFS) univariable and multivariable Cox analyses were performed. In the latter, due to the low number of cases and events, penalized likelihood was applied, and variable selection was performed using a random forest model. RESULTS: Sixty-seven patients were included. With a median follow-up of 50.2 months, 51 (76%) patients developed PD and 16 (24%) remained stable. PD at treatment start did not meet RECIST version 1.1 in 15/51 (29%) patients. The 3-year PFS and OS were 25.4% and 71.1%, respectively, in the whole population. Tumour-related pain (TRP) was the most common baseline symptom (32.8%), followed by temperature (20.9%), fatigue (17.9%), and weight loss (16.4%). Baseline TRP (P = 0.0002), development of TRP during follow-up (P = 0.005), baseline temperature (P = 0.002), and development of fatigue during follow-up (P = 0.007) were associated with a significantly worst PFS. An association between baseline TRP (P < 0.0001), development of TRP during follow-up (P = 0.0009), evidence of baseline serosal effusion (P = 0.121), and OS was recorded. CONCLUSION: Because of the poor outcome observed in EHE patients presenting with serosal effusion, TRP, temperature, or serosal effusion, upfront treatment in this subgroup could be considered.
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Hemangioendotelioma Epitelioide , Adulto , Hemangioendotelioma Epitelioide/diagnóstico , Humanos , Italia/epidemiología , Pronóstico , Criterios de Evaluación de Respuesta en Tumores Sólidos , Estudios RetrospectivosRESUMEN
BACKGROUND: Percutaneous biopsy is recommended before surgery for suspected retroperitoneal sarcoma (RPS) to confirm the histological diagnosis and guide surgical strategy. The present study aimed to establish the diagnostic accuracy of percutaneous core biopsy with respect to histological diagnosis and tumour grade. METHODS: Data on patients with suspected RPS who underwent percutaneous biopsy followed by surgical resection between 2005 and 2016 at one of two tertiary European sarcoma units were reviewed. Histological tumour type and tumour grade on biopsy were correlated with postoperative histology to evaluate diagnostic accuracy. RESULTS: A total of 239 patients underwent percutaneous core biopsy followed by surgical resection in Milan (163, 68·2 per cent) or Birmingham (76, 31·8 per cent). Diagnostic accuracy varied with histological diagnosis (P < 0·001), but demonstrated overall concordance with final pathology following resection in 67·2 per cent of biopsies (κ = 0·606). The majority of discrepancies occurred in dedifferentiated liposarcoma (DDLPS), owing to under-recognition of dedifferentiation in this group. Concordance between pathology on biopsy and resection improved to 81·1 per cent when DDLPS and well differentiated liposarcoma were grouped together as liposarcoma. Grade on biopsy was concordant with grade on resection specimen in 60·4 per cent of tumours (κ = 0·640). Diagnosis of high-grade tumours on biopsy had a high specificity (98 per cent), and moderate positive predictive value (85 per cent) and negative predictive value (78 per cent). CONCLUSION: A diagnosis of DDLPS or leiomyosarcoma on percutaneous biopsy is highly reliable. High-grade sarcomas can be identified with high specificity, which opens the door to a study on neoadjuvant therapy in these patients.
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Biopsia con Aguja Gruesa/métodos , Leiomiosarcoma/patología , Liposarcoma/patología , Liposarcoma/cirugía , Neoplasias Retroperitoneales/patología , Neoplasias Retroperitoneales/cirugía , Adulto , Anciano , Estudios de Cohortes , Bases de Datos Factuales , Supervivencia sin Enfermedad , Femenino , Hospitales Universitarios , Humanos , Italia , Leiomiosarcoma/mortalidad , Leiomiosarcoma/cirugía , Liposarcoma/mortalidad , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Neoplasias Retroperitoneales/mortalidad , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento , Reino UnidoRESUMEN
BACKGROUND: To explore the activity of axitinib in advanced solitary fibrous tumour (SFT). PATIENTS AND METHODS: In this investigator-driven phase II study on axitinib in advanced and progressive SFT, patients received axitinib, 5 mg bis in day (BID), until progression or limiting toxicity. Pathologic diagnosis was centrally reviewed, distinguishing malignant SFT (M-SFT) and high-grade/dedifferentiated SFT (HG/D-SFT) subtypes. The primary end-point was the overall response rate (ORR) by Choi criteria (Choi). Secondary end-points were response by Response Evaluation Criteria in Solid Tumours (RECIST), progression-free survival (PFS) and overall survival (OS). RESULTS: From April 2015 and October 2017, 17 eligible patients entered the study (metastatic: 17; SFT subtype: 13 M-SFT, 4 HG/D-SFT; prior treatment: 9 antiangiogenics, 5 cytotoxics). All patients were evaluable for response. The best Choi response was seven partial response (PR) (ORR, 41.2%), six stable disease (SD) and four progressions. Choi-ORR was 54% (7/13) when only M-SFTs were considered. Four of seven responsive patients were pretreated with pazopanib. No responses were detected in HG/D-SFT. Best RECIST response was one PR (5.9%), 14 SD and two progressions. Toxicity was as expected. Median Choi-PFS was 5.1 (interquartile range [IQR]: 2.5-14.8) months. Median Choi-PFS was 14.8 (IQR: 5.1-18.0) and 2.8 (IQR: 2.0-5.9) months for patients responsive and non-responsive by Choi, respectively (p = 0.0416). At a 14.4-month median follow-up, median OS was 25.3 months. CONCLUSION: This study showed that axitinib is active in progressive advanced SFT. One-half of patients carrying the malignant variant of the disease responded, with a >12-month median progression arrest. Responses were better detected with Choi and seen even in patients resistant to other antiangiogenics. Tolerability was good.
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Inhibidores de la Angiogénesis/uso terapéutico , Axitinib/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Tumores Fibrosos Solitarios/tratamiento farmacológico , Adulto , Anciano , Inhibidores de la Angiogénesis/efectos adversos , Axitinib/efectos adversos , Progresión de la Enfermedad , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Inhibidores de Proteínas Quinasas/efectos adversos , Criterios de Evaluación de Respuesta en Tumores Sólidos , Tumores Fibrosos Solitarios/mortalidad , Tumores Fibrosos Solitarios/secundario , Factores de TiempoRESUMEN
BACKGROUND: Preclinical models that mimic pathological and molecular features of solitary fibrous tumour (SFT) represent an important tool to select effective regimes and novel compounds to be tested in the clinic. This study was aimed at developing two preclinical models of SFT, assessing their predictive value in the clinic and selecting potential novel effective treatments. MATERIAL AND METHODS: Two dedifferentiated-SFT (D-SFT) models obtained from patients' biopsies were grown in immunodeficient mice. The antitumour activity on these models of doxorubicin, dacarbazine (DTIC), ifosfamide (monotherapy or combination), trabectedin and eribulin was tested. Twelve SFT patients were treated with doxorubicin and DTIC. Response by RECIST, progression-free survival and overall survival were retrospectively evaluated, distinguishing malignant-SFT (M-SFT) and D-SFT. RESULTS: Two D-SFT patient-derived xenografts (PDXs) that represent the first available preclinical in vivo models of SFT were developed and characterised. Doxorubicin/DTIC, DTIC/ifosfamide, doxorubicin/ifosfamide combinations consistently induced better antitumour activity than the single-agents. Particularly, doxorubicin/DTIC combination caused a max tumour volume inhibition >80% in both models. Doxorubicin/DTIC combo showed activity also in the case-series. Best RECIST responses were: 6 responses (M-SFT = 2 of 7, D-SFT = 4 of 5), 1 stable disease, 5 progressions, with a 6-month median progression-free survival (M-SFT = 6, D-SFT = 10 months). The PDXs were very sensitive to trabectedin and eribulin. CONCLUSION: Doxorubicin plus DTIC combination was effective in our two D-SFT mice models and appeared to be active also in the clinic, especially in high-grade D-SFT patients. Among additional drugs tested in the PDXs, trabectedin and eribulin were highly effective, providing a rational to test these drugs in D-SFT patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Cerebelosas/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Neoplasias Meníngeas/tratamiento farmacológico , Neoplasias Pleurales/tratamiento farmacológico , Neoplasias Retroperitoneales/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Tumores Fibrosos Solitarios/tratamiento farmacológico , Adulto , Anciano , Animales , Western Blotting , Neoplasias Cerebelosas/mortalidad , Dacarbazina/administración & dosificación , Dioxoles/administración & dosificación , Supervivencia sin Enfermedad , Doxorrubicina/administración & dosificación , Femenino , Furanos/administración & dosificación , Humanos , Ifosfamida/administración & dosificación , Cetonas/administración & dosificación , Neoplasias Renales/mortalidad , Masculino , Neoplasias Meníngeas/mortalidad , Ratones SCID , Persona de Mediana Edad , Neoplasias Pleurales/mortalidad , Criterios de Evaluación de Respuesta en Tumores Sólidos , Neoplasias Retroperitoneales/mortalidad , Estudios Retrospectivos , Neoplasias de los Tejidos Blandos/mortalidad , Tumores Fibrosos Solitarios/mortalidad , Tasa de Supervivencia , Tetrahidroisoquinolinas/administración & dosificación , Trabectedina , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Chordomas are rare, malignant bone tumors of the skull-base and axial skeleton. Until recently, there was no consensus among experts regarding appropriate clinical management of chordoma, resulting in inconsistent care and suboptimal outcomes for many patients. To address this shortcoming, the European Society of Medical Oncology (ESMO) and the Chordoma Foundation, the global chordoma patient advocacy group, convened a multi-disciplinary group of chordoma specialists to define by consensus evidence-based best practices for the optimal approach to chordoma. In January 2015, the first recommendations of this group were published, covering the management of primary and metastatic chordomas. Additional evidence and further discussion were needed to develop recommendations about the management of local-regional failures. Thus, ESMO and CF convened a second consensus group meeting in November 2015 to address the treatment of locally relapsed chordoma. This meeting involved over 60 specialists from Europe, the United States and Japan with expertise in treatment of patients with chordoma. The consensus achieved during that meeting is the subject of the present publication and complements the recommendations of the first position paper.
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Cordoma/terapia , Guías de Práctica Clínica como Asunto , Humanos , Recurrencia Local de NeoplasiaRESUMEN
Although retroperitoneal sarcomas are rare tumours, they can be encountered by a wide variety of clinicians as they can be incidental findings on imaging or present with non specific symptoms and signs. Surgical resection can offer hope of cure and patient outcomes are improved when patients are managed in high-volume specialist centers. Failure to recognize retroperitoneal sarcomas on imaging can lead to inappropriate management in inexperienced centers. Therefore it is critical that a diagnosis of retroperitoneal sarcoma should be considered in the differential diagnosis of a retroperitoneal mass with prompt referral to a soft tissue sarcoma unit. In particular, the most common retroperitoneal sarcoma subtypes, liposarcoma and leiomyosarcoma, have characteristic imaging appearances which are discussed. This review therefore aims to set the context and guide clinicians through a diagnostic pathway for retroperitoneal masses in adults which arise extrinsic to the solid abdominal viscera.
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Algoritmos , Neoplasias Retroperitoneales/diagnóstico por imagen , Neoplasias Retroperitoneales/patología , Sarcoma/diagnóstico por imagen , Sarcoma/patología , Tomografía Computarizada por Rayos X , Biopsia con Aguja Gruesa , Medios de Contraste , Diagnóstico Diferencial , Humanos , Biopsia Guiada por Imagen , Imagen por Resonancia Magnética , Neoplasias Retroperitoneales/terapia , Sarcoma/terapiaRESUMEN
BACKGROUND: Pre-clinical and clinical evidence suggests a rationale for the use of anti-angiogenic agents, including sorafenib, in recurrent and/or metastatic salivary gland carcinomas (RMSGCs). This study evaluates the activity of sorafenib in patients with RMSGCs and also investigates whether the activity of sorafenib could be related to its main tailored targets (i.e. BRAF, vascular endothelial growth factor receptor 2 [VEGFR2], platelet-derived growth factor receptor α [PDGFRα] and ß, RET, KIT). PATIENTS AND METHODS: Patients received sorafenib at 400 mg BID. The primary end-point was response rate (RR) including complete response or partial response (PR); secondary end-points included RR according to Choi criteria, disease control rate (DCR), overall survival (OS), and progression-free survival (PFS). RESULTS: Thirty-seven patients (19 adenoid cystic cancers, ACC) were enrolled. Six PRs were recorded. RR was 16% (95% confidence interval [CI]: 6-32; 11% in ACC and 22% in non-ACC). Choi criteria could be applied in 30 out of 37 cases with a RR of 50% (95% CI: 31-69%); DCR was 76% (95% CI: 59-88%). Incidence of ≥G3 adverse events was 29.7%. Median PFS and OS for the entire population were 5.9 months and 23.4 months, respectively. Median PFS and OS were 8.9 and 26.4 months for ACC versus 4.2 and 12.3 months for non-ACC patients. All the cases showed expression of PDGFRß in the stroma and VEGFR2 in endothelial cells; PDGFRα positivity was found in the stroma of four (27%) cases. All except for two cases showed no PDGFRß, VEGFR2 and PDGFRα expression in the tumour cells. KIT expression was restricted to ACC and a weak RET expression was limited to one adenocarcinoma, not otherwise specified (NOS). No BRAF mutation was found. No correlation was observed between the sorafenib activity and the expression of its markers although all six responders (two ACC, one adenocarcinoma, NOS, one salivary duct cancer [SDC], one high-grade mucoepidermoid [HG-MEC] and one poorly-differentiated cancer) are enriched in the stromal component showing a PDGFRß immunodecoration. In ACCs, immunohistochemistry revealed MYB protein expression in 15/16 cases (94%) and the MYB-NFIB fusion oncogene was observed in 9/14 (64%). CONCLUSIONS: Sorafenib is the first anti-angiogenic agent to demonstrate activity in RMSGC patients, particularly in some histotypes such as HG-MEC, SDC and adenocarcinoma, NOS. The PDGFRß-positive rich stromal component characterising these histotypes and the lack of correlation between the activity of sorafenib and its targets suggests anti-angiogenic effect as the prevalent mechanism of action of sorafenib in SGCs.
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Adenocarcinoma/tratamiento farmacológico , Antineoplásicos/uso terapéutico , Carcinoma Adenoide Quístico/tratamiento farmacológico , Carcinoma Mucoepidermoide/tratamiento farmacológico , Mioepitelioma/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Neoplasias de las Glándulas Salivales/tratamiento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adenocarcinoma/secundario , Adulto , Anciano , Carcinoma Adenoide Quístico/metabolismo , Carcinoma Adenoide Quístico/patología , Carcinoma Adenoide Quístico/secundario , Carcinoma Mucoepidermoide/metabolismo , Carcinoma Mucoepidermoide/patología , Carcinoma Mucoepidermoide/secundario , Diarrea/inducido químicamente , Supervivencia sin Enfermedad , Erupciones por Medicamentos/etiología , Fatiga/inducido químicamente , Síndrome Mano-Pie/etiología , Humanos , Hipertensión/inducido químicamente , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Mioepitelioma/metabolismo , Mioepitelioma/patología , Mioepitelioma/secundario , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/metabolismo , Niacinamida/uso terapéutico , Proteínas Proto-Oncogénicas c-kit/metabolismo , Proteínas Proto-Oncogénicas c-ret/metabolismo , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Neoplasias de las Glándulas Salivales/metabolismo , Neoplasias de las Glándulas Salivales/patología , Sorafenib , Tasa de Supervivencia , Resultado del Tratamiento , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Adulto JovenRESUMEN
BACKGROUND: To report on long-term results of a phase 3 trial comparing three versus five cycles of adjuvant chemotherapy (CT) with full-dose epirubicin+ifosfamide in high-risk soft tissue sarcomas (STS). METHODS: Patients (pts) were randomized to receive three preoperative cycles of epirubicin 120 mg/m2 and ifosfamide 9 g/m2 (Arm A) or to receive the same three preoperative cycles plus two postoperative cycles (Arm B). Radiotherapy could be either delivered in the preoperative or in the postoperative setting. Non-inferiority of the primary end point, OS, was assessed by the confidence interval of the hazard ratio (HR; Arm A/Arm B) derived from Cox model. RESULTS: Between January 2002 and April 2007, 164 pts were assigned to arm A and 164 to arm B. At a median follow-up (FU) of 117 months (IQ range 103-135 months), 123 deaths were recorded: 58 in Arm A and 65 in Arm B. Ten-year OS was 61% for the entire group of patients: 64% in Arm A and 59% in Arm B. The intention-to-treat analysis confirmed that three cycles were not inferior to five cycles (one-sided 95% upper confidence limit was 1.24). A per protocol analysis was consistent with these results. Pts with leiomyosarcoma and undifferentiated pleomorphic sarcoma (UPS) had the lowest, and the highest response rates, respectively. Consistently, Leiomyosarcoma and UPS had the worse and the best prognosis, respectively. CONCLUSIONS: At a longer FU, the non-inferiority of three cycles of a full-dose conventional CT in comparison to five is confirmed. Response to therapy is also confirmed to be associated with better survival. This regimen is currently tested within an ongoing international trial against three cycles of a neoadjuvant histology-tailored CT (ClinicalTrials.gov Identifier: NCT01710176).
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Quimioterapia Adyuvante , Leiomiosarcoma/tratamiento farmacológico , Pronóstico , Sarcoma/tratamiento farmacológico , Adulto , Anciano , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Leiomiosarcoma/patología , Leiomiosarcoma/radioterapia , Masculino , Persona de Mediana Edad , Factores de Riesgo , Sarcoma/patología , Sarcoma/radioterapia , Resultado del TratamientoRESUMEN
At present, there is no standardised approach for the radiological evaluation of soft tissue sarcomas following radiotherapy (RT). This manuscript, produced by a European Organisation for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) and Imaging Group endorsed task force, aims to propose standardisation of magnetic resonance imaging techniques and interpretation after neoadjuvant RT for routine use and within clinical trials.
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Imagen por Resonancia Magnética/normas , Oncología por Radiación/normas , Sarcoma/patología , Sarcoma/radioterapia , Neoplasias de los Tejidos Blandos/patología , Neoplasias de los Tejidos Blandos/radioterapia , Consenso , Humanos , Valor Predictivo de las Pruebas , Radioterapia Adyuvante/normas , Reproducibilidad de los Resultados , Resultado del TratamientoRESUMEN
PURPOSE: The aim of this study was to optimize the dosimetric approach and to review the absorbed doses delivered, taking into account radiobiology, in order to identify the optimal methodology for an individualized treatment planning strategy based on (99m)Tc-macroaggregated albumin (MAA) single photon emission computed tomography (SPECT) images. METHODS: We performed retrospective dosimetry of the standard TheraSphere® treatment on 52 intermediate (n = 17) and advanced (i.e. portal vein thrombosis, n = 35) hepatocarcinoma patients with tumour burden < 50% and without obstruction of the main portal vein trunk. Response was monitored with the densitometric radiological criterion (European Association for the Study of the Liver) and treatment-related liver decompensation was defined ad hoc with a time cut-off of 6 months. Adverse events clearly attributable to disease progression or other causes were not attributed to treatment. Voxel dosimetry was performed with the local deposition method on (99m)Tc-MAA SPECT images. The reconstruction protocol was optimized. Concordance of (99m)Tc-MAA and (90)Y bremsstrahlung microsphere biodistributions was studied in 35 sequential patients. Two segmentation methods were used, based on SPECT alone (home-made code) or on coregistered SPECT/CT images (IMALYTICS™ by Philips). STRATOS™ absorbed dose calculation was validated for (90)Y with a single time point. Radiobiology was used introducing other dosimetric variables besides the mean absorbed dose D: equivalent uniform dose (EUD), biologically effective dose averaged over voxel values (BEDave) and equivalent uniform biologically effective dose (EUBED). Two sets of radiobiological parameters, the first derived from microsphere irradiation and the second from external beam radiotherapy (EBRT), were used. A total of 16 possible methodologies were compared. Tumour control probability (TCP) and normal tissue complication probability (NTCP) were derived. The area under the curve (AUC) of the receiver-operating characteristic (ROC) curve was used as a figure of merit to identify the methodology which gave the best separation in terms of dosimetry between responding and non-responding lesions and liver decompensated vs non-decompensated liver treatment. RESULTS: MAA and (90)Y biodistributions were not different (71% of cases), different in 23% and uncertain in 6%. Response correlated with absorbed dose (Spearman's r from 0.48 to 0.69). Responding vs non-responding lesion absorbed doses were well separated, regardless of the methodology adopted (p = 0.0001, AUC from 0.75 to 0.87). EUBED gave significantly better separation with respect to mean dose (AUC = 0.87 vs 0.80, z = 2.07). Segmentation on SPECT gave better separation than on SPECT/CT. TCP(50%) was at 250 Gy for small lesion volumes (<10 cc) and higher than 1,000 Gy for large lesions (>10 cc). Apparent radiosensitivity values from TCP were around 0.003/Gy, a factor of 3-5 lower than in EBRT, as found by other authors. The dose-rate effect was negligible: a purely linear model can be applied. Toxicity incidence was significantly larger for Child B7 patients (89 vs 14%, p < 0.0001), who were therefore excluded from dose-toxicity analysis. Child A toxic vs non-toxic treatments were significantly separated in terms of dose averaged on whole non-tumoural parenchyma (including non-irradiated regions) with AUC from 0.73 to 0.94. TD50 was ≈ 100 Gy. No methodology was superior to parenchyma mean dose, which therefore can be used for planning, with a limit of TD15 ≈ 75 Gy. CONCLUSION: A dosimetric treatment planning criterion for Child A patients without complete obstruction of the portal vein was developed.
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Carcinoma Hepatocelular/terapia , Embolización Terapéutica , Vidrio/química , Neoplasias Hepáticas/terapia , Microesferas , Planificación de la Radioterapia Asistida por Computador/métodos , Radioisótopos de Itrio , Carcinoma Hepatocelular/diagnóstico por imagen , Niño , Relación Dosis-Respuesta en la Radiación , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Medicina de Precisión , Radiobiología , Radiometría , Estudios Retrospectivos , Agregado de Albúmina Marcado con Tecnecio Tc 99m , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
AIM: This study aimed to characterize Supermoto performance by correlating the fastest lap (best performance) with heart rate (HR), anthropometric characteristics, racing experience and the ratings of perceived exertion (RPE) of riders. METHODS: Twenty Supermoto riders - data are shown as mean value±standard deviation (SD), age: 29±9 years, BMI: 23.0±2.4, riding experience: 4±3 years - performed 12 laps on a circuit 1167 m long, without off-road part, but data were available for 16 riders. The HR was monitored throughout all laps, RPE was asked at the end of the race. The fastest rider wore a portable metabolic unit to assess the aerobic load of Supermoto riding. RESULTS: The HRmean was related to the best performance (r=0.747, P<0.001). The correlation between HR and the best performance was not mediated by racing experience, even though the latter correlated negatively with lap times (r=-0.548, P<0.050). The RPE and anthropometric characteristics did not correlate with best performance. Average-to-slow riders showed a higher HR than fastest riders (delta-HRmean: 20 beats·min(-1), P=0.010). The aerobic load during Supermoto riding was 4.29±1.50 METs (at 60% of HRmax) and a mean VO2 1142±398 mL·min-1. During the race simulation the rider had a HR 15% higher than during the lap with the metabolic unit, hence a mean MET around 5.3 was estimated during the race. CONCLUSION: In conclusion, HR reflects performance in Supermoto racing independently from racing experience and it is lower in faster riders. Elevated HR seems not to be explained entirely by the aerobic load.
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Rendimiento Atlético/fisiología , Conducta Competitiva/fisiología , Frecuencia Cardíaca/fisiología , Motocicletas , Consumo de Oxígeno/fisiología , Resistencia Física , Esfuerzo Físico/fisiología , Adulto , Antropometría , Femenino , Humanos , Italia , MasculinoRESUMEN
OBJECTIVES: Aim of study was to assess the correlation between computed tomography scan (CT) findings and histopathology. MATERIAL AND METHODS: Data were collected on consecutive patients with suspected retroperitoneal sarcoma (RPS) referred to a tertiary sarcoma center. Patients underwent contrast enhanced multi-detector CT scans. Radiological features of lesions were classified according to the presence of a fatty (Group A) mass, or non-fatty (Group B) mass, both subdivided according to homogeneity and intralesional high-contrasted appearance. Radiological classification was compared with histopathological diagnosis. Sensitivity, specificity, positive/negative predictive value (PPV, NPV) were analyzed. RESULTS: Of 291 patients, 103/291 (35.4%) masses were classified in Group A and 188/291 (64.6%) in Group B. Diagnosis of mesenchymal tumor was obtained in 231/291 cases (79%) and non-mesenchymal tumor in 60/291 (21%). Sensitivity and specificity of Group A for liposarcoma were 76.7% and 92.0%; PPV and NPV were 86.4% and 85.6%. Sensitivity of Group B for a mesenchymal tumor was 55.4% and specificity was 0%; PPV and NPV were 68.1% and 0%. CONCLUSIONS: None of radiological criteria were sufficient to anticipate a specific diagnosis, with the only exception of well differentiated liposarcoma and angiomyolipoma. In a series of suspected RPS, 21% of the lesions were finally non-mesenchymal tumors.
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Neoplasias Retroperitoneales/diagnóstico por imagen , Neoplasias Retroperitoneales/patología , Tomografía Computarizada por Rayos X , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Angiomiolipoma/diagnóstico por imagen , Angiomiolipoma/patología , Femenino , Fibromatosis Agresiva/diagnóstico por imagen , Fibromatosis Agresiva/patología , Tumores del Estroma Gastrointestinal/diagnóstico por imagen , Tumores del Estroma Gastrointestinal/patología , Humanos , Leiomiosarcoma/diagnóstico por imagen , Leiomiosarcoma/patología , Liposarcoma/diagnóstico por imagen , Liposarcoma/patología , Masculino , Persona de Mediana Edad , Mielolipoma/diagnóstico por imagen , Mielolipoma/patología , Neurilemoma/diagnóstico por imagen , Neurilemoma/patología , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: To explore the activity of pazopanib in solitary fibrous tumour (SFT). PATIENTS AND METHODS: In a preclinical study, we compared the activity of pazopanib, sorafenib, sunitinib, regorafenib, axitinib and bevacizumab in a dedifferentiated-SFT (DSFT) xenotransplanted into Severe Combined Immunodeficiency (SCID) mice. Antiangiogenics were administered at their reported optimal doses when mean tumour volume (TV) was 80 mm(3). Drug activity was assessed as TV inhibition percentage (TVI%). From May 2012, six consecutive patients with advanced SFT received pazopanib, on a national name-based programme. In one case sunitinib was administered after pazopanib failure. RESULTS: In the xenograft model, pazopanib showed the lowest antitumour activity (21%TVI), while regorafenib was the most active (95%TVI). Sorafenib, bevacizumab, sunitinib were markedly active (78/70/65%TVI). Axitinib was marginally active (51%TVI). In the retrospective case-series, three patients carried malignant-SFT (MSFT), three DSFT. Best Response Evaluation Criteria in Solid Tumour (RECIST) responses were: three stable disease (SD), all MSFT, three progressive disease (PD), all DSFT, corresponding to one partial response (PR), two SD, three PD by Choi criteria. Median-progression-free survival was 3 months (range 1-15). In one patient, sunitinib was started after pazopanib failure, with a response. CONCLUSIONS: In dedifferentiated-SFT xenograft pazopanib induced a marginal antitumour activity, while regorafenib appeared the most active and promising agent. When administered in patients, pazopanib showed a modest activity in terms of tumour growth stabilisation, observed only in non-dedifferentiated cases.