RESUMO
PURPOSE: To evaluate the prognostic role of pretreatment 18F-FDG PET/CT metabolic parameters in non-endemic Epstein-Barr Virus (EBV DNA)-related nasopharyngeal cancer (NPC) patients treated with curative intensity-modulated radiation therapy (IMRT) with or without chemotherapy (CHT). MATERIALS/METHODS: We retrospectively reviewed clinical data of 160 consecutive non-metastatic NPC patients who received IMRT with or without CHT. Forty-nine out of 160 patients that underwent whole body 18F-FDG PET/CT at our institution for disease staging with a minimum follow-up to 12 months were included in this study. We evaluated the relationship between maximum and mean standardized uptake values (SUVmax and SUVmean, respectively), metabolic tumor volume and total lesion glycolysis (TLG) of primary tumor and cervical lymph nodes with disease-free survival (DFS) and overall survival (OS). We also investigated the prognostic role of clinical variables such as age, disease stage, plasma EBV DNA load (copies/ml), gross tumor volume of primary tumor and lymph nodes. RESULTS: Median follow-up was 55 months. Two- and 5-year OS were 95.8% and 90.5%, respectively, while DFS was 83.4% at both time points. SUVmax of primary tumor ≥ 18.8 g/ml and primary tumor TLG ≥ 203.1 g were significant prognostic factors of worse OS. Furthermore, stages IVB and EBV DNA load ≥ 3493 copies/ml were significantly associated with lower DFS. No correlation was found between PET parameters and plasma EBV DNA load. CONCLUSION: Even in a limited series, our data suggested that SUVmax, SUVmean and TLG of primary tumor could predict a poor outcome in NPC patients also in non-endemic area hypothesizing their use for refinement of prognostication.
Assuntos
DNA Viral/sangue , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/radioterapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Radioterapia de Intensidade Modulada , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Terapia Combinada , Feminino , Fluordesoxiglucose F18 , Herpesvirus Humano 4 , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/virologia , Estadiamento de Neoplasias , Prognóstico , Interpretação de Imagem Radiográfica Assistida por Computador , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Carga Viral , Imagem Corporal TotalRESUMO
BACKGROUND: The aim of this study was to report on sirolimus activity in a series of patients with hemangioendothelioma (HE) treated at the National Cancer Institute, Milan (Istituto Nazionale Tumori; INT) and within the Italian Rare Cancer Network ("Rete Tumori Rari"; RTR). METHODS: We retrospectively reviewed patients with advanced and progressing epithelioid hemangioendothelioma (EHE) treated with sirolimus at the INT and/or within the RTR. Pathologic review and molecular analysis for WWTR1 rearrangement were performed. Sirolimus was administered until unacceptable toxicity or progression, with the dose being adjusted to reach target plasma levels of 15-20 ng/dL. Responses were assessed using the Response Evaluation Criteria In Solid Tumors (RECIST) criteria. RESULTS: Since 2005, 18 patients (17 EHE, 1 retiform HE; 1 locally advanced, 17 metastatic; WWTR1 rearrangement: 16) have been identified, with 17/18 patients being evaluable for response. Mean sirolimus daily dose was 4.5 mg. According to RECIST, best responses in EHE were 1 partial response (PR), 12 stable disease (SD), and 3 progressive disease (PD); the patient with retiform HE also achieved a PR, lasting >2 years. Four patients with a reversed interval progression on interruption were observed. Median overall survival was 16 months, and median progression-free survival was 12 months (range 1-45), with four patients progression-free at 24 months. The clinical benefit (complete response [CR] + PR + SD >6 months) was 56 %. Seven patients receiving sirolimus experienced an increase in pleural/peritoneal effusion plus worsening of tumor-related symptoms; six of these patients died within 1-8 months from evidence of effusion progression, while a RECIST PD was assessed in two of seven patients. CONCLUSIONS: A clinical benefit was achieved in 56 % of patients receiving sirolimus, which lasted >24 months in four patients. Most patients with pleural effusion did not benefit from sirolimus and had a poor outcome.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Hemangioendotelioma Epitelioide/tratamento farmacológico , Hemangioendotelioma Epitelioide/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Sirolimo/uso terapêutico , Adulto , Idoso , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/sangue , Líquido Ascítico , Bases de Dados Factuais , Progressão da Doença , Intervalo Livre de Doença , Rearranjo Gênico , Hemangioendotelioma Epitelioide/secundário , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Derrame Pleural/induzido quimicamente , Critérios de Avaliação de Resposta em Tumores Sólidos , Estudos Retrospectivos , Sirolimo/efeitos adversos , Sirolimo/sangue , Taxa de Sobrevida , Transativadores , Fatores de Transcrição , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Progress in developing effective salvage therapies for UC is warranted. Alisertib is an orally available, selective inhibitor of the aurora kinase A. METHODS: A single-group, phase 2 trial was conducted with alisertib 50 mg orally BID for 7 days, with 14d rest until disease progression (PD) (NCT02109328). The primary endpoint (EP) was RECIST 1.1 objective response-rate (ORR, H0 ≤ 5%, H1 ≥ 20%, α = 10% and ß = 20%). Eligibility included failure of at least one platinum-based regimen. RESULTS: From 10/2014 to 04/2015, 22 patients were enrolled (20 evaluable for response), 8 (36.4%) in second-line and 14 (63.6 %) beyond the second-line. Eight (36.4%) had an ECOG-performance status 1-2. Two partial responses (PR, ORR: 9.1%), 7 stable disease (SD) and 11 PD were obtained. Median follow-up was 8.3 months (IQR: 7-10.3), 6-month progression-free survival (PFS) was 13.6% (95%CI: 4.8-39.0). Two SD are still receiving treatment after 11.5 and 6.3 months. Median overall survival (OS) was not reached (6-month OS: 59.1%, 95%CI: 41.7-83.7). Hb < 10 g/dl was significantly associated with shorter PFS and OS multivariably (p = 0.031 and p = 0.033). Tissue of the case with 11.5 month SD harbored a missense mutation of mTOR (E1813D), the nonsense mutation Q527STOP of TSC1, HER3 and TAF1L missense mutations. Grade 3-4 adverse events (AE) were: 40.9% mucositis, 36.4% fatigue, 18.2% neutropenia (13.6% febrile neutropenia). There were 2 treatment-related deaths. CONCLUSIONS: The study did not meet the primary EP, yet sustained disease control was obtained in about 14% of patients. The incidence of AE and the issue of patient selection are two major concerns.
Assuntos
Aurora Quinase A/antagonistas & inibidores , Azepinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia , Idoso , Aurora Quinase A/metabolismo , Azepinas/efeitos adversos , Azepinas/farmacologia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/efeitos adversos , Pirimidinas/farmacologia , Resultado do Tratamento , Urotélio/efeitos dos fármacosRESUMO
PURPOSE: We evaluated whether (18)F-3'-deoxy-3'-fluorothymidine positron emission tomography (FLT PET) can predict the final postoperative histopathological response in primary breast cancer after the first cycle of neoadjuvant chemotherapy (NCT). METHODS: In this prospective cohort study of 15 patients with locally advanced operable breast cancer, FLT PET evaluations were performed before NCT, after the first cycle of NCT, and at the end of NCT. All patients subsequently underwent surgery. Variables from FLT PET examinations were correlated with postoperative histopathological results. RESULTS: At baseline, median of maximum standardized uptake values (SUVmax) in the groups showing a complete pathological response (pCR) + residual cancer burden (RCB) I, RCB II or RCB III did not differ significantly for the primary tumour (5.0 vs. 2.9 vs. 8.9, p = 0.293) or for axillary nodes (7.9 vs. 1.6 vs. 7.0, p = 0.363), whereas the Spearman correlation between SUVmax and Ki67 proliferation rate index was significant (r = 0.69, p < 0.001). Analysis of the relative percentage change of SUVmaxin the primary tumour (∆SUVTmax(t1)) and axillary nodes (∆SUVNmax(t1)) after the first NCT cycle showed that the power of ∆SUVTmax(t 1) to predict pCR + RCB I responses (AUC = 0.91, p < 0.001) was statistically significant, whereas ∆SUVNmax(t1) had a moderate ability (AUC = 0.77, p = 0.119) to separate subjects with ΔSUVTmax(t1) > -52.9 % into two groups: RCB III patients and a heterogeneous group that included RCB I and RCB II patients. A predictive score µ based on ΔSUVTmax(t1) and ΔSUVNmax(t1) parameters is proposed. CONCLUSION: The preliminary findings of the present study suggest the potential utility of FLT PET scans for early monitoring of response to NCT and to formulate a therapeutic strategy consistent with the estimated efficacy of NCT. However, these results in a small patient population need to be validated in a larger independent cohort.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Didesoxinucleosídeos , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios X , Adulto , Neoplasias da Mama/radioterapia , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Projetos PilotoRESUMO
BACKGROUND: Clear cell sarcoma (CCS), initially named malignant melanoma of soft parts, is an aggressive soft tissue sarcoma (STS) that, due to MITF activation, shares with melanoma the expression of melanocyte differentiation antigens. CCS is poorly sensitive to chemotherapy. Multi-kinase inhibitors have been used as therapeutic agents. In the case we report here, treatment with sunitinib induced a long-lasting clinical response that was associated with an immune activation directed against Melan-A/MART-1 antigen. CASE PRESENTATION: A 28 years old female patient with an advanced molecularly confirmed CCS resistant to conventional chemotherapy was started in January 2012 on sunitinib, 37.5 mg/day, with evidence of radiologic and metabolic response at the primary and metastatic sites of disease. Pathologic response and loss of the Melan-A/MART-1 antigen were evidenced on residual tumor removed in April 2012. Immunological monitoring performed on patient's blood during pharmacological treatment revealed a systemic, Melan-A/MART-1 specific immunity and a low frequency of immunosuppressive cells. Sunitinib was restarted in May 2012, with a new response, and continued for 11 months although with repeatedly interruptions due to toxicity. Disease progression and new responses were documented at each treatment interruption and restart. Sunitinib was definitively interrupted in April 2013 for disease progression. CONCLUSION: The analysis of this case proves that antigens expressed by CCS, as for melanoma, can be immunogenic in vivo and that tumor-antigen specific T cells may exert anti-tumor activity in CCS patient. Thus, manipulation of the immune response may have therapeutic potential for this STS subtype and immunotherapy approaches, can be promising therapeutic options for these patients.
Assuntos
Antígeno MART-1/imunologia , Proteínas de Fusão Oncogênica/genética , Sarcoma de Células Claras/genética , Sarcoma de Células Claras/imunologia , Fatores de Transcrição/genética , Adulto , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/metabolismo , Antineoplásicos/uso terapêutico , Feminino , Humanos , Imunofenotipagem , Indóis/uso terapêutico , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Pirróis/uso terapêutico , Sarcoma de Células Claras/diagnóstico , Sarcoma de Células Claras/tratamento farmacológico , Sunitinibe , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Patients with relapsed and refractory Hodgkin lymphoma (HL) may experience long-term survival after allogeneic stem cell transplantation (alloSCT), but disease recurrence represents the main cause of treatment failure. Positron-emission tomography (PET)-positive patients after alloSCT have a dismal outcome. Serum thymus and activation-regulated chemokine (TARC) is produced by Reed-Sternberg cells and may be a marker of disease. Our study aimed at assessing whether TARC levels after alloSCT correlated with disease status and whether TARC monitoring could increase the ability to predict relapse. Twenty-four patients were evaluated in a prospective observational study. TARC serum level and PET were assessed before and after alloSCT during the follow-up (median, 30 months; range, 2 to 54). Before alloSCT, the median TARC level was 721 pg/mL (range, 209 to 1332) in PET-negative patients and 2542 pg/mL (range, 94 to 13,870) in PET-positive patients. After alloSCT, TARC was 620 pg/mL (range, 12 to 4333) in persistently PET-negative patients compared with 22,397 pg/mL (range, 602 to 106,578) in PET-positive patients (P < .0001). In 7 patients who relapsed after alloSCT, TARC level increased progressively even before PET became positive, with a median fold increase of 3.19 (range, 1.66 to 7.11) at relapse. The cut-off value of 1726 pg/mL had a sensitivity of 100% and a specificity of 71% for PET positivity. Patients with at least 1 TARC value above 1726 pg/mL during the first year after alloSCT had a worse progression-free survival (P = .031). In conclusion, TARC was correlated with disease status and its monitoring may be able to predict PET positivity after alloSCT, thus potentially allowing an early immune manipulation.
Assuntos
Quimiocina CCL17/sangue , Doença de Hodgkin , Monitorização Fisiológica , Tomografia por Emissão de Pósitrons , Transplante de Células-Tronco , Adolescente , Adulto , Aloenxertos , Intervalo Livre de Doença , Feminino , Doença de Hodgkin/sangue , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/mortalidade , Doença de Hodgkin/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Recidiva , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
OBJECTIVES: Our aim was to assess FDG-PET/CT as a surrogate biomarker of the pathological complete response in locally advanced rectal cancer treated with neoadjuvant chemoradiation. METHODS: T3-4 and/or N+ rectal cancer patients were treated prospectively with capecitabine-based chemoradiation and total mesorectal excision 7-8 weeks later. FDG-PET/CT uptake was obtained at baseline, after 2 weeks, and 6 weeks following treatment completion, calculating the maximum standardized uptake value (SUV) and percentage difference to identify the early and late metabolic 'response index'. RESULTS: Thirty-one patients were treated from January 2009 to January 2012 at the Istituto Nazionale dei Tumori of Milan. One patient was excluded due to surgery refusal. The pathological complete response rate was 30%. Early FDG-PET/CT was performed in 24 consenting patients and failed to show predictive utility. On the contrary, significant differences in late SUV value and response index were observed between complete and noncomplete pathological responders (p = 0.0006 and 0.03). In multivariate analysis including most relevant SUV parameters, none of them was independently associated with a pathological complete response. With receiver operating characteristic curve analysis, a late SUV threshold <5.4 had 81% sensitivity and 100% specificity, with 90% overall accuracy. CONCLUSIONS: We evidenced a possible predictive role of late FDG-PET/CT for the assessment of pathological response in locally advanced rectal cancer following neoadjuvant chemoradiation.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/patologia , Neoplasias Retais/radioterapia , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Capecitabina , Quimiorradioterapia , Desoxicitidina/uso terapêutico , Feminino , Fluordesoxiglucose F18 , Fluoruracila/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/normas , Análise Multivariada , Terapia Neoadjuvante , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Compostos Radiofarmacêuticos , Resultado do TratamentoRESUMO
AIM: To analyze the patterns of locoregional failure following intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) at our institution, as part of an internal quality assurance program. We aimed to investigate the potential existence of a correlation between any part of the IMRT process and clinical outcome. METHODS & MATERIALS: A total of 106 non-metastatic NPC patients consecutively treated with IMRT (with or without chemotherapy) were analyzed. Radiotherapy was administered using a sequential or simultaneous integrated boost approach at the total prescribed dose of 66-70 Gy (2.00-2.12 Gy per fraction). MRI studies of recurrences were recorded with the planning computed tomography studies to identify volume of failure. Recurrence-related characteristics were analyzed with respect to the original treatment. Failures were classified as 'in-field', 'marginal' or 'out-field' if at least 95, 20-95 or less than 20% of the volume of failure, respectively, was within 95% of the total prescription dose. RESULTS: With a median follow-up of 43.4 months, 5-years local control, regional control, locoregional control and overall survival rates were 87.7, 88.0, 83.5 and 81.3% respectively. A total of 21 failures were registered in 15 patients. In particular, ten failures (47.6%) were classified as 'in-field' (seven local failures and three regional failures [RFs]), nine failures (42.9%) as 'marginal' (five local failures and four RFs) and only two failures (9.5%) as 'out-field' (both RFs). The most relevant causes of failures were suboptimal target definition and target coverage as well as a longer than planned overall treatment time. CONCLUSION: IMRT determines excellent outcome in NPC patients. However, great attention in all IMRT steps is necessary to reduce potential causes of failure.
Assuntos
Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidade Modulada , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/mortalidade , Estadiamento de Neoplasias , Planejamento da Radioterapia Assistida por Computador , Recidiva , Falha de Tratamento , Adulto JovemRESUMO
BACKGROUND: The development of new drugs for patients with refractory urothelial cancer is still an unmet medical need. Preclinical evidence lends support to a rationale for targeting of the VEGF or platelet-derived growth-factor axis. We therefore investigated the activity and safety of pazopanib, a multitarget drug with antiangiogenic activity, in patients with urothelial cancer. METHODS: In an open-label, single-group, phase 2 study, patients (aged ≥18 years) with relapsed or refractory urothelial cancer were given pazopanib 800 mg per day, orally. They were treated until disease progression or prohibitive toxicity occurred. The primary endpoint was the proportion of patients who achieved a confirmed objective response, defined as complete or partial response, after independent review, and was analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT01031875. FINDINGS: The trial has been completed. 21 (51%) of 41 patients enrolled were given pazopanib as third-line or further-line treatment. 26 (63%) patients had an Eastern Cooperative Oncology Group performance status of 1 or 2. Seven patients had a confirmed objective response (17·1%, 95% CI 7·2-32·1), all of which were partial responses. The most frequent treatment-related grade 3 adverse events were hypertension (three [7%]), fatigue (two [5%]), and gastrointestinal and vaginal fistulisations (two each [5%]). One patient died as a result of duodenal fistulisation that was related to tissue response of bulky tumour masses. INTERPRETATION: Pazopanib has single-agent activity in patients with heavily pretreated metastatic urothelial cancer, and warrants further study in this setting. Particular attention should be paid to patients with bulky tumour masses adjacent to viscera because fistulisation is probably related to the response to pazopanib and is the most frequent serious adverse event. FUNDING: Fondazione IRCCS Istituto Nazionale dei Tumori provided the grant. GlaxoSmithKline provided the study drug and provided funding for the independent radiological review.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Neoplasias Urológicas/tratamento farmacológico , Urotélio/efeitos dos fármacos , Administração Oral , Idoso , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Indazóis , Itália , Estimativa de Kaplan-Meier , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Modelos de Riscos Proporcionais , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Medição de Risco , Fatores de Risco , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral , Neoplasias Urológicas/mortalidade , Neoplasias Urológicas/patologia , Urotélio/patologiaRESUMO
PURPOSE: Alveolar soft part sarcoma (ASPS) is a rare, chemoresistant soft tissue sarcoma. ASPS harbors the t(17-X) (p11.2;q25) translocation, resulting in the ASPACR1-TFE3 fusion protein, causing MET autophosphorylation and activation of downstream signaling. The tumor vascular pattern prompted us to use sunitinib malate (SM), a tyrosine kinase inhibitor with antiangiogenic properties. EXPERIMENTAL DESIGN: Since July 2007, five patients with progressive metastatic ASPS have been treated with continuous SM 37.5 mg/d on a named basis. Four patients are evaluable for response. In four cases, cryopreserved material was available. Upstream and downstream targets of receptor tyrosine kinase (RTK) pathways, as well as mechanisms of activation, were investigated by biochemical profiles, including human phospho-receptor RTK antibody arrays and immunoprecipitation/Western blotting, molecular analyses, immunohistochemistry, and fluorescence in situ hybridization analyses. RESULTS: After 3 months, two patients had RECIST (response evaluation criteria in solid tumor) partial response, as well as positron emission tomography response and subjective improvement. One had a RECIST stable disease. One progressed and stopped treatment. One patient is still responding after 12 months. The upstream analysis showed activation of all the platelet-derived growth factor receptor (PDGFR) family members, as well as epidermal growth factor receptor, MET families, and RET. Vascular endothelial growth factor receptors (VEGFR1 and VEGFR2) were activated only in one case. The downstream target analysis showed strong activation of phosphatidylinositol 3-kinase/AKT, extracellular signal-regulated kinase 1/2, and mTOR and its targets (S6K and S6). The absence of any upstream mTOR effector deregulation and the presence of RTK cognate ligands support an autocrine-paracrine activation loop mechanism. CONCLUSION: SM may have antitumor activity in ASPS, possibly through a mechanism involving PDGFR and RET. The role of MET, epidermal growth factor receptor, and mTOR, as well as PDGFR inhibition, needs to be further explored.
Assuntos
Indóis/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirróis/uso terapêutico , Sarcoma Alveolar de Partes Moles/tratamento farmacológico , Adulto , Avaliação de Medicamentos , Receptores ErbB/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosforilação , Proteínas Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Receptores do Fator de Crescimento Derivado de Plaquetas/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Sarcoma Alveolar de Partes Moles/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sunitinibe , Serina-Treonina Quinases TORRESUMO
Despite the considerable technological advances in imaging modalities which have occurred over the last years, EUS remains one of the most reliable and accurate technique for the study of gastroenteropancreatic neuroendocrine tumors. More specifically, EUS can detect very small lesions, assess the local extent and lymph node involvement and biopsy the lesion for cytophatological confirmation (EUS-FNA). In addition, nuclear medicine imaging has a relevant role in the evaluation of NET. However, its performance depends on series of patient-specific features (lesion size and uptake, depth and other anatomic features; metabolic activity, receptor expression, affinity and vacancy, tissue specificity) and technical features (choice of tracer, administered dose, and physical half-life; instrument sensitivity, acquisition technique, reader experience). In particular, current data show that PET/CT has greater intrinsic resolution and sensitivity than SPECT or SPECT/CT images resulting in improved tumor detection. However, the PET tracer of choice has not yet been identified. 18F-FDG has proved to be useful as indicator of tumor aggressiveness rather than detection of extent of disease, and 68Ga-DOTA-TOC has demonstrated good results in clinical trials. 11C-5HTP has performed well in limited trials, but the 20-min half life of 11C precludes widespread availability. Better information concerning biodistribution and further comparative data of these agent in larger clinical trials are warranted.
Assuntos
Tumores Neuroendócrinos/diagnóstico , 5-Hidroxitriptofano , Biópsia por Agulha Fina , Carbono , Meios de Contraste , Diagnóstico por Imagem/métodos , Di-Hidroxifenilalanina/análogos & derivados , Endossonografia , Fluordesoxiglucose F18 , Gadolínio , Humanos , Tumores Neuroendócrinos/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Eribulin mesylate (E) is indicated for metastatic breast cancer patients previously treated with anthracycline and taxane. We argued that E could also benefit patients eligible for neoadjuvant chemotherapy. METHODS: Patients with primary triple negative breast cancer ≥2 cm received doxorubicin 60 mg/m2 and paclitaxel 200 mg/m2 x 4 cycles (AT) followed by E 1.4 mg/m2 x 4 cycles. Primary endpoint was pathological complete response (pCR) rate; secondary and explorative endpoints included clinical/metabolic response rates and safety, and biomarker analysis, respectively. Using a two-stage Simon design, 43 patients were to be included provided that 4 of 13 patients had achieved pCR in the first stage of the study. RESULTS: In stage I of the study 13 women were enrolled, median age 43 years, tumor size 2-5 cm in 9/13 (69%), positive nodal status in 8/13 (61%). Main grade 3 adverse event was neutropenia (related to AT and E in 4 and 2 cases, respectively). AT followed by E induced clinical complete + partial responses in 11/13 patients (85%), pCR in 3/13 (23%). Median measurements of maximum standardized uptake value (SUVmax) resulted 13, 3, and 1.9 at baseline, after AT and E, respectively. Complete metabolic response (CMR) occurred after AT and after E in 2 and 3 cases, respectively. Notably, 2 of the 5 (40%) patients with CMR achieved pCR at surgery. Immunostaining of paired pre-/post-treatment tumor specimens showed a reduction of ß-catenin, CyclinD1, Zeb-1, and c-myc expression, in the absence of N-cadherin modulation. The study was interrupted at stage I due to the lack of the required patients with pCR. CONCLUSIONS: Despite the early study closure, preoperative E following AT showed clinical and biological activity in triple negative breast cancer patients. Furthermore, the modulation of ß-catenin pathway core proteins, supposedly outside the domain of epithelial-mesenchymal transition, claims for further investigation. TRIAL REGISTRATION: EU Clinical Trial Register, EudraCT number 2012-004956-12.
Assuntos
Furanos/uso terapêutico , Cetonas/uso terapêutico , Terapia Neoadjuvante/métodos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adulto , Antraciclinas/uso terapêutico , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Feminino , Humanos , Taxoides/uso terapêutico , Resultado do TratamentoRESUMO
Following up on the Consensus Conference on high-grade malignant salivary gland tumours (HGMSGT) in adult patients in Brescia, Italia, in October 2014, we review the current imaging modalities for diagnosing and staging these rare tumours. The advantages of functional MR imaging techniques such as diffusion weighted imaging (DWI) and dynamic contrast-enhanced MR imaging (DCEMRI) in comparison with traditional MRI will be outlined. The limited role of (18)FDG-PET CT and fMRI will be addressed. Finally, in view of new experimental treatment options, we will discuss the role of imaging during follow-up.
Assuntos
Neoplasias das Glândulas Salivares/patologia , Biópsia por Agulha , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias das Glândulas Salivares/diagnóstico por imagemRESUMO
AIMS AND BACKGROUND: Primary cytoreductive surgery (CRS) has a significant impact on prognosis in epithelial ovarian cancer (EOC). Patient selection is important to recognize factors limiting optimal CRS and to avoid unnecessary aggressive surgical procedures. We evaluated the contribution of fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in the presurgical identification of disease sites that may preclude EOC cytoreducibility. METHODS: Patients with suspected EOC underwent 18F-FDG-PET/CT within 20 days before debulking surgery. The PET/CT results were compared with surgical findings and postsurgery histopathology in order to assess the diagnostic value. RESULTS: Between August 2013 and January 2014, 29 patients were evaluated. The histopathology showed 23 EOC and 6 benign tumors. The FDG-PET/CT was positive (maximum standardized uptake value [SUVmax] 11.3 ± 5.4) in 21/23 (91%) patients with EOC and provided 2 false-negatives (1 mucinous and 1 clear cell carcinoma; SUVmax ≤2.8). The FDG-PET/CT was true-negative (SUVmax 2.2 ± 1.6) in 4 out of 6 patients (67%). False-positive FDG-PET results were obtained in 2 cellular fibromas (SUVmax 4.8 and 5.6). The sensitivity, specificity, and accuracy of PET/CT to characterize ovarian masses were 91%, 67%, and 86%, respectively. Among the 21 FDG-PET/CT-positive EOC, we detected factors limiting optimal CRS in 6 cases (29%): 4 hepatic hilum infiltration and 2 root mesentery involvement, confirmed at surgical exploration. The FDG-PET did not find limiting factors in the remaining 15 patients (71%) in whom optimal CRS was obtained. CONCLUSIONS: Fluorodeoxyglucose-PET/CT shows high sensitivity but suboptimal specificity in the characterization of ovarian masses. However, PET/CT may play a role in noninvasively selecting patients with EOC who can benefit from primary CRS.
Assuntos
Carcinoma/diagnóstico , Carcinoma/cirurgia , Procedimentos Cirúrgicos de Citorredução , Neoplasias Epiteliais e Glandulares/diagnóstico , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/patologia , Carcinoma Epitelial do Ovário , Feminino , Fluordesoxiglucose F18/administração & dosagem , Humanos , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Seleção de Pacientes , Tomografia por Emissão de Pósitrons/métodos , Valor Preditivo dos Testes , Prognóstico , Compostos Radiofarmacêuticos/administração & dosagem , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: In patients with metastatic seminoma, designing a risk-adapted strategy that may help personalize the burden of treatment and follow-up is required. PATIENTS AND METHODS: Patients who were administered cisplatin, etoposide, and bleomycin (PEB) were staged at baseline with computed tomography (CT), positron emission tomography (PET), and serum tumor markers. Restaging was then performed with PET after 2 cycles of PEB (PET2) and with CT after 3 to 4 cycles of treatment. The 20% cutoff of maximal standardized uptake value (SUVmax) changes and Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) criteria were applied to define the response. The Wilcoxon rank sum test was used to analyze the association between metabolic response and the shrinkage of target lesions. RESULTS: Between February 2009 and November 2013, 37 patients were enrolled. After 2 cycles of PEB, 27 patients (72.9%; 95% confidence interval [CI], 55.8-86.2) had a metabolic complete response (CR) and 10 patients had a partial response (PR; 27%; 95% CI, 13.8-44.1). A significant association was found between PET2 response and baseline (P = .003), final diameter (P < .001), and percentage of tumor shrinkage (P = .014) of target lesions. After 18 months' (interquartile range [IQR], 13-23) median follow-up, 2 patients with PET2 PR had relapsed disease; none of those with a CR had relapsed disease. CONCLUSIONS: A significant association was found between early metabolic response and tumor shrinkage in patients with advanced seminoma. Patients achieving a PET2 CR could be predicted not to need additional treatment after PEB, and simplifying their follow-up should be an end point. PET2 might also identify difficult to treat cases at an early stage.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Seminoma/diagnóstico por imagem , Neoplasias Testiculares/diagnóstico por imagem , Adulto , Bleomicina/administração & dosagem , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Fluordesoxiglucose F18/farmacocinética , Humanos , Masculino , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/farmacocinética , Seminoma/tratamento farmacológico , Seminoma/secundário , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/patologia , Distribuição Tecidual , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacosRESUMO
BACKGROUND: Patients with WHO grade II glioma may respond to chemotherapy that is currently not standardized regarding timing and treatment duration. Metabolic changes during chemotherapy may precede structural tumor volume reductions. We therefore compared time courses of amino acid PET and MRI responses to temozolomide (TMZ) and assessed whether responses correlated with seizure control and progression-free survival (PFS). METHODS: PET and MRI were performed before and during TMZ chemotherapy. Tumor volumes were calculated using regions-of-interest analysis. Amino acid uptake was also quantified as metabolically active tumor volume and tumor-to-cerebellum uptake ratio. RESULTS: One hundred twenty-five PET and 125 MRI scans from 33 patients were analyzed. Twenty-five patients showed metabolic responses that exhibited an exponential time course with a 25% reduction of the active volume on average after 2.3 months. MRI responses followed a linear course with a 25% reduction after 16.8 months. Reduction of metabolically active tumor volumes, but not reduction of PET uptake ratios or MRI tumor volumes, correlated with improved seizure control following chemotherapy (P = .012). Receiver-operating-characteristic curve analysis showed that a decrease of the active tumor volume of ≥80.5% predicts a PFS of ≥60 months (P = .018) and a decrease of ≥64.5% a PFS of ≥48 months (P = .037). CONCLUSIONS: Amino acid PET is superior to MRI for evaluating TMZ responses in WHO grade II glioma patients. The response delay between both imaging modalities favors amino acid PET for individually tailoring the duration of chemotherapy. Additional studies should investigate whether this personalized approach is appropriate with regard to outcome.
Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Adulto , Aminoácidos , Antineoplásicos/uso terapêutico , Área Sob a Curva , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/mortalidade , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Intervalo Livre de Doença , Feminino , Glioma/tratamento farmacológico , Glioma/mortalidade , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Curva ROC , Convulsões/etiologia , Sensibilidade e Especificidade , Temozolomida , Adulto JovemRESUMO
Sentinel lymph node (SLN) sampling is an attractive alternative to complete lymphadenectomy. Based on the identification and sampling of the first LN draining a primary tumor, SLN biopsy is the most accurate and the only reliable method for microscopic nodal staging for solid tumors including breast cancer and melanoma. Lymph node status in pelvic tumors remains the most important prognostic factor for recurrence and survival and a major decision criterion for adjuvant therapy. We review the clinical indications, controversies, and perspective of SLN biopsy in male and female pelvic cancers.
Assuntos
Neoplasias Pélvicas/diagnóstico , Neoplasias Pélvicas/patologia , Biópsia de Linfonodo Sentinela/métodos , Diagnóstico por Imagem , Humanos , Neoplasias Pélvicas/diagnóstico por imagem , Neoplasias Pélvicas/cirurgia , Período Pré-OperatórioRESUMO
BACKGROUND: Since glucose represents the preferred fuel for cancer cells, there is some debate about the potential stimulation of tumour metabolism induced by a glucose-based total parenteral nutrition (TPN) in cancer patients. METHODS: We investigated the uptake of [18]2-fluoro-2-deoxy-D-glucose (FDG) through the positron emission tomography of the healthy liver and of the tumour in 12 patients with liver metastases from colorectal cancer. We determined whether FDG uptake by the tumour in fasting conditions was affected by the subsequent administration of a glucose-based (GTPN) or a lipid-based (LTPN) containing glucose 4 mg/kg/min or lipid 2 mg/kg/min, respectively, as non-protein energy source. RESULTS: The data showed that FDG uptake by the metastases was 3-3.6 times higher than by the healthy liver in fasting conditions and it was not significantly affected by the subsequent administration of GTPN or LTPN. CONCLUSIONS: We speculated that, despite glucose being the preferred fuel for cancer cells, its disproportionately high uptake even in fasting conditions makes the glucose consumption unable to be modulated by a further supply of glucose or lipid.
Assuntos
Neoplasias Colorretais/metabolismo , Glucose/metabolismo , Neoplasias Hepáticas/metabolismo , Nutrição Parenteral Total , Adulto , Idoso , Glicemia/metabolismo , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/terapia , Jejum/metabolismo , Feminino , Fluordesoxiglucose F18/metabolismo , Glucose/administração & dosagem , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/metabolismo , Tomografia Computadorizada de EmissãoRESUMO
The most widely used diagnostic nuclear medicine technique in well-differentiated thyroid cancer (DTC) is radioiodine scintigraphy, either diagnostic or post-therapeutic, together with serum thyroglobulin (Tg) measurement; this combination is usually able to determine the presence or absence of cancer. FDG-PET has shown less sensitivity in DTC that retains the ability to trap 131I. Several alternative procedures with single photon emitting radiopharmaceuticals have been evaluated including whole body scan with 201Tl, 99mTc-sestamibi or tetrofosmin scan, with different sensitivity and specificity. The main advantage of these tests is that their results are not influenced by the levels of TSH, therefore they do not require a hypothyroid state in the patient. Recently positron emission tomography (PET) with FDG has been demonstrated to be highly useful in thyroid cancer patients with a negative 131I whole body scan but measurable Tg. According to reports in the literature FDG-PET in the follow-up of operated patients has a sensitivity ranging from 70% to 90% in identifying the source of Tg. The demonstration of lesions can lead to a change in treatment including surgery or external radiation instead of radioiodine treatment. In Europe, medullary thyroid cancer (MTC) is currently visualized by 99mTc pentavalent dimercaptosuccinic acid (DMSA) and 99mTc-sestamibi or tetrofosmin. Metaiodobenzylguanidine (MIBG) radiolabeled with 123I or 131I is another reliable radiopharmaceutical for medullary tumors. (111)In-pentetreotide scan is positive in a high percentage of patients because MTC expresses somatostatin receptors. FDG-PET has an interesting role to play in calcitonin-positive patients, where PET has been shown to correctly identify lesions in cervical and mediastinal lymph nodes as well as at distant sites. Furthermore, calcitonin-guided PET has been found to be superior to CT and MRI in many patients. Recent reports indicated that 18F-DOPA scan in MTC seems to be more accurate than FDG-PET.