Neutrophil to lymphocyte ratio as a prognosis biomarker of PRRT in NET patients.

PURPOSE: Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-DOTATATE is a palliative therapeutic option for advanced Neuroendocrine Tumors (NETs). Prognostic factors can predict long-term outcomes and determine response to therapy. Among those already explored, biomarkers from full blood count, including neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) has shown value for other solid tumors and for NETs patients submitted to other forms of therapy. However, its relation to PRRT response and patients' prognosis is still to be determined. METHODS: Medical records from 96 patients submitted to PRRT between 2010 and 2017 were reviewed, median NLR and PLR were calculated from baseline flood blood count and dichotomized as high or low. Progression-free survival (PFS) and Overall Survival (OS) were calculated. RESULTS: NLR and PLR median values were 1.8 and 123, respectively. Patients with low NLR had a significantly longer OS (estimated median of 77.5 months, 95% CI: 27.3-127.7) when compared to patients with high NLR (estimated median of 47.7 months, 95% CI: 34.7-60.8); p = 0.04. Patients with low NLR had a trend toward a longer median PFS when compared to patients with high NLR [estimated medians of 77 months (95% CI: 27.3-127.7), and 47.7 months, (95% CI: 34.7-60.7)], respectively, p = 0.08. CONCLUSION: Patients with advanced-stage NET with NLR higher than 1.8 have worse long term clinical outcomes after PPRT. Larger studies are needed to validate the optimal cutoff for this biomarker.

High thyroglobulin and negative whole-body scan: no long-term benefit of empiric radioiodine therapy.

PURPOSE: Around 10-27% of patients will present elevated thyroglobulin (Tg) levels and negative diagnostic whole-body scan (dxWBS) during differentiated thyroid cancer (DTC) follow-up. Empiric radioactive iodine (RAI) therapy in this context is controversial due to the lack of good quality studies in the context. The main purpose of this study is to compare long-term response to therapy status and overall survival between empiric RAI treated and untreated DTC patients. METHODS: A retrospective study comparing differentiated thyroid cancer patients with negative diagnostic whole-body scan and elevated thyroglobulin levels submitted or not to empiric radioactive iodine therapy in a thyroid cancer referral center. The main outcome measures were ATA Response to Therapy Stratification at 6-12 months after RAI ablative dose, at 6-18 months after negative dxWBS and last follow-up visits. RESULTS: Overall, 120 DTC patients with stimulated Tg >10 ng/ml and negative dxWBS were included in this study. Overall, 53 patients were submitted to empiric RAI and 67 were in the control group. No difference was observed in ATA Response to Therapy Stratification after RAI ablation or at the end of follow-up between groups. Also, no difference was found in terms of Tg changes response. After more than 10 years of follow-up, 17 patients died (13 from treated and 4 from untreated group). CONCLUSIONS: Empiric RAI treatment was not associated with better long-term ATA response to therapy status or overall survival.

Fluorine-18-fluorodeoxyglucose PET/CT in hematopoietic stem cell transplant patients with fusariosis: initial findings of a case series review.

BACKGROUND: Fusariosis is an opportunistic fungal infection that affects mostly leukemic and hematopoietic stem cell transplant patients. Locally invasive and disseminated infection may occur. Treatment is challenging, and besides evaluation of immune status, one also needs to take into account organ involvement to predict the duration and prognosis. OBJECTIVE: The aim of this study was to present the findings and clinical follow-up from a series of cases of Fusarium spp. infections in patients subjected to hematopoietic stem cell transplant evaluated with one or more fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT scans, according to the source of clinical culture sample (blood or wound secretion). RESULTS: Ten patients were included. In this series, 18F-FDG PET/CT was able to detect osteomyelitis in three patients. CONCLUSION: Although having a small number of patients and lack of standard approach, 18F-FDG PET/CT seemed useful to discriminate uncomplicated cases of primary bloodstream infections and detect occult foci of metastatic infection in patients with positive cutaneous lesions cultures.

A phase I study of mTOR inhibitor everolimus in association with cisplatin and radiotherapy for the treatment of locally advanced cervix cancer: PHOENIX I.

BACKGROUND: Cervix cancer (CC) represents the fourth most common cancer in women. Treatment involving cisplatin and radiotherapy has been the standard for locally advanced disease. Everolimus inhibits the aberrant activity of mTOR that is part of carcinogenesis in CC. Further everolimus inactivates the HPV E7 oncoprotein and inhibits its proliferation. Preclinical models have suggested that everolimus sensitizes tumoral cells and vasculature to cisplatin and radiotherapy. METHODS: In a 3 + 3 design, the trial aimed to treat three dose levels of at least three patients with daily doses of everolimus (2.5, 5 and 10 mg/day), cisplatin and radiotherapy delivered in a 9-week interval in CC patients, stage IIB, IIIA or IIIB. Patients received everolimus from day -7 up to the last day of brachytherapy. Primary objective was to evaluate safety, toxicity and the maximum-tolerated dose (MTD) of everolimus in association with cisplatin and radiotherapy. Pharmacokinetic (PK) parameters and response rates were analyzed as secondary objectives. RESULTS: Thirteen patients were enrolled, 6 at 2.5 mg, 3 at 5 mg and 4 at 10 mg. Four patients did not complete the planned schedule, 1 at 2.5 mg presented grade 4 acute renal failure interpreted as dose-limiting toxicity (DLT) and 3 at 10 mg: 1 with disease progression, and 2 with DLTs-1 grade 3 rash and 1 grade 4 neutropenia. PK results were characterized by dose-dependent increases in AUC and C max. CONCLUSIONS: The MTD of everolimus in combination with cisplatin and radiotherapy has been defined as 5 mg/day. The data regarding safety and response rates support further studies.

Is there a role for peptide receptor radionuclide therapy in medullary thyroid cancer?

BACKGROUND: Medullary thyroid cancer (MTC) is a rare but potentially life-threatening disease with limited therapeutic options. As a neuroendocrine tumor, MTC expresses somatostatin receptors, and therefore, somatostatin-labeled radiopharmaceuticals could be used to treat patients with MTC. OBJECTIVE: The aims of this study were to evaluate tumor shrinkage after Lu-DOTATATE treatment, to analyze the impact on quality of life as accessed by the SF-36 questionnaire, and to demonstrate a possible prognostic role for In-DTPA-octreotide uptake in patients with MTC. PATIENTS AND METHODS: Patients with progressive MTC underwent evaluation using In-DTPA-octreotide. Patients who demonstrated In-DTPA-octreotide uptake were treated with 4 cycles of 200 mCi of Lu-DOTATATE and were evaluated using CT scans over 8 to 12 months of treatment. RESULTS: Of the 16 patients initially enrolled, 9 (56.25%) had lesions that were observed in the In-DTPA-octreotide scans and were eligible for therapy with Lu-DOTATATE. Three patients had a partial response, 3 patients were classified as having stable disease and, 1 patient had a progressive disease. All responders indicated improvement in quality of life 6 to 12 months after therapy. CONCLUSIONS: Treatment with Lu-DOTATATE seems to be an alternative therapy for somatostatin receptor-positive tumors, with very mild adverse effects and quality-of-life improvement, at least during a short-term period. Further studies are needed to determine long-term benefits and to identify which patients are more likely to respond to this modality of therapy.

[Cost analysis of18F-FDG PET-CT from the perspective of the Brazilian Unified National Health System as healthcare provider: a study in a public healthcare center in Rio de Janeiro, Brazil]. / Análise dos custos do procedimento PET-TC com 18 F-FDG na perspectiva do SUS provedor: estudo em uma unidade pública de saúde do Rio de Janeiro, Brasil.

Positron emission tomography (PET) has been introduced recently in Brazil and requires costs analysis to support economic evaluation studies on its use. The current study analyzed the use of 18 F-FDG PET-CT and estimated its costs from the perspective of a public healthcare provider. The micro-costing technique was used, identifying, quantifying, and valuing all the inputs used to perform the procedure. Cost estimates considered 85 tests performed at the Brazilian National Cancer Institute from March to June 2012. Reference cases were defined as adult cancer patients, output of five tests per day, and one dose of 18 F-FDG per patient. Unit cost for the procedure was BRL 3,150.30 based on career wages under the Ministry of Science and Technology and BRL 2,927.19 based on Ministry of Health career wages. The factor with the heaviest cost impact was daily output of tests. Other factors that could impact the test's cost in public healthcare institutions were also examined.

Análise dos custos do procedimento PET-TC com 18 F-FDG na perspectiva do SUS provedor: estudo em uma unidade pública de saúde do Rio de Janeiro, Brasil / Cost analysis of 18 F-FDG PET-CT from the perspective of the Brazilian Unified National Health System as healthcare provider: a study in a public healthcare center in Rio de Janeiro, Brazil / Análisis de costes del procedimiento PET-TC con 18 F-FDG desde la perspectiva del SUS proveedor: estudio en una unidad pública de salud de Río de Janeiro, Brasil

A tomografia de emissão de pósitrons (PET) é de uso recente no Brasil e há necessidade de se estimar os custos do procedimento, de forma a subsidiar estudos de avaliação econômica sobre a tecnologia. O trabalho analisou o processo de produção da PET-TC utilizando 18 F-FDG e estimou seus custos na perspectiva de um provedor público de serviços de saúde. Utilizou- se a técnica de microcustos, com identificação, quantificação e valoração de todos os insumos consumidos na produção do procedimento. As estimativas de custo consideraram a observação de 85 exames realizados no Instituto Nacional de Câncer, de março/julho de 2012. O caso de referência considerou pacientes oncológicos adultos, volume de produção de 5 exames/dia e uso de uma dose de 18 F-FDG por paciente. Os custos unitários do procedimento foram de R$ 3.150,30, na perspectiva salarial da carreira de Ciência & Tecnologia, e de R$ 2.927,19 na do Ministério da Saúde. O elemento de maior impacto nos custos correspondeu ao volume diário de produção dos exames. Foram explorados elementos que podem impactar no custo do exame nas instituições públicas de saúde.

Positron emission tomography (PET) has been introduced recently in Brazil and requires costs analysis to support economic evaluation studies on its use. The current study analyzed the use of 18 F-FDG PET-CT and estimated its costs from the perspective of a public healthcare provider. The micro-costing technique was used, identifying, quantifying, and valuing all the inputs used to perform the procedure. Cost estimates considered 85 tests performed at the Brazilian National Cancer Institute from March to June 2012. Reference cases were defined as adult cancer patients, output of five tests per day, and one dose of 18 F-FDG per patient. Unit cost for the procedure was BRL 3,150.30 based on career wages under the Ministry of Science and Technology and BRL 2,927.19 based on Ministry of Health career wages. The factor with the heaviest cost impact was daily output of tests. Other factors that could impact the test’s cost in public healthcare institutions were also examined.

La tomografía por emisión de positrones (PET) es de uso reciente en Brasil y es necesario estimar sus costes, con el fin de subsidiar estudios de evaluación económica sobre esta tecnología. El trabajo examina el proceso de producción de PET-TC con 18F-FDG y se estimaron sus costes desde la perspectiva de un prestador público de servicios de salud. Se empleó la técnica de microcostes, con la identificación, cuantificación y valoración de los insumos consumidos en la producción del procedimiento. Las estimaciones consideran la observación de 85 exámenes entre marzo y julio de 2012. El “caso base” considera pacientes adultos de cáncer, con una producción de 5 exámenes/día y el uso de una dosis de 18F-FDG por paciente. Los costes unitarios del procedimiento fueron, respectivamente, R$ 3.150.30 y R$ 2.927.19, desde la perspectiva del Ministerio de Ciencia y Tecnología y del Ministerio de Salud. El volumen diario de producción fue el elemento de mayor impacto en los costes. Además, se analizaron los factores que pueden repercutir en el coste del examen en instituciones de salud pública.

Recovery coefficients determination for partial volume effect correction in oncological PET/CT images considering the effect of activity outside the field of view.

OBJECTIVES: The partial volume effect (PVE) has a great impact in quantitative PET/CT imaging. Correction methods have been recently proposed by many authors to make the image quantification more accurate. This work presents a methodology for determining the recovery coefficients (RCs) for PVE correction in PET/CT images. It was taken into account the radioactivity outside the field of view (FOV), which is expected in a patient image acquisition. METHODS: The NEMA image quality phantom and the NEMA scatter phantom were used. The phantoms were filled with (18)F-FDG for different sphere-to-background ratios. The RCs have been determined from image acquisitions in a Siemens Biograph 16 Hi-Rez PET/CT scanner with and without the scatter phantom. RESULTS: The RC values that ranged from 0.38 to 1.00 without the scatter phantom exhibited a wider variation when this latter was taken into account (from 0.27 to 1.02). This more realistic estimation must be considered if one takes into account that an incorrect SUV measure in tumors leads to errors in the evaluation of the response to therapy based on PET/CT images. CONCLUSIONS: The activity outside the FOV should be considered in RCs determination to improve the RC-based PVE correction method.

Whole-body MRI and FDG PET fused images for evaluation of patients with cancer.

OBJECTIVE: The purpose of this article is to illustrate the feasibility of fused whole-body MRI and PET for the evaluation of patients with cancer. CONCLUSION: MRI has proven to be superior to CT for studying several regions of the body, and PET FDG has become an established diagnostic tool in oncology. Because FDG accumulates avidly in tumor tissue, fusing FDG PET to whole-body MRI allows good anatomy-based evaluation of disease.

Utility of [(18)F] fluoro-2-deoxy-D: -glucose positron emission tomography in the localization of ectopic ACTH-secreting tumors.

Ectopically ACTH producing tumors may be difficult to localize by conventional radiology and functional imaging may be helpful. Case 1: 31-year-old man was diagnosed with ectopic ACTH-dependent Cushing's syndrome (ECS). Thorax CT revealed a 1.3 cm nodular opacity in upper left lobe, suggestive of residual lesion. [(18)F] fluoro-2-deoxy-D: -glucose ([(18)F] FDG) positron emission tomography ([(18)F] FDG PET) scan revealed mild glycolytic metabolic activity. Pathological examination confirmed an ACTH-positive carcinoid tumor. Case 2: 53-year-old woman presented with very rapid onset ECS. Pituitary MRI was normal. Thorax CT revealed no tumoral lesion. Abdominal and pelvic MRI showed images suggestive of hepatic and iliac, femoral and lumbar secondary implants. [(18)F] FDG PET scan revealed intense uptake in uterus, especially cervix, suggesting this to be the primary tumor site. These cases illustrate the role of [(18)F] FDG PET in the investigation of an ECS where conventional imaging studies were not elucidative in the search for a responsible tumor.

Acesso subcranial minimamente invasivo: alternativa cirúrgica para ressecção de tumores da base do crânio anterior / Minimally invasive subcranial approach: a surgical alternative for the ressection of anterior skull base tumors

Objetivo: descrever e anlisar nossa experiência em ressecção de tumores craniofaciais através de um acesso subcranial modificado, minimamente invasivo, desenvolvido por nós. Pacientes e método: estudo prospectivo com 26 pacientesapresentando tumores pequenos na base do crânio anterior, trtados nas Seções de Cirurgia de Cabeça e Pescoço e de Neurocirurgia do INCA-MS-RJ, no período de março de 2000 a setembro de 2006, operados pela mesma equipe cirúrgica, utilizando a técnica inovadora subcranial minimamente invasiva. Comparamos nossos resultados com resultados já publicados em literatura dos nossos pacientes submetidos à cirurgia craniofacial clássica, assim como com dados de literatura mundia. Resultados: dos 26 pacientes, 14 eram do gênero masculino. A idade média foi de 45,7 anos. O acesso subcranial isolado sem incisões faciais foi utilizado em seis casos. O tempo cirúrgico médio foi de 8,38 horas. A média de internação na unidade de terapia intensiva foi de 1,2 dias e de internação hospitalar de 7,8 dias. Não observamos complicações neurológicas imediatas. O índice de complicações foi de 28,5% com mortalidade operatória nula. A sobrevida global (para tumores malignos) foi de 61,9%. Conclusão: trata-se de um acesso inovador, onde podemos observar alguns benefícios notáveis, como a redução de complicações neurológicas gerais, tendência a reduzir o tempo cirúrgico, baixa taxa de hemotransfusão, menor tempo de internação em terapia intensiva e hospitalar e praticabilidade para tumores faciais acometendo o platô cribiforme ou discreta invasão da fossa craniana anterior.

Objective: to describe and to analyze our experience with the resection of craniofacial tumors throughe a modified minimally invasive subcranial access, developed by us. Patients and methods: prospective study with 26 patients presenting small tumors in the anterior skull base, treated in the Section of Head and Neck Surgery and Neurosurgery (INCA-MS-RJ), in the period from March, 2000 to September, 2006. The same surgical team was responsible for all surgeries using the innovative minimally invasive surgical technique. We compare the results of this technique with the results already published in the literature of our own patients treated by the classic cranialfacial technique, as well as, with data of worldwide literature. Results: of the 26 patients, 14 were men. The average age was of 45.7. The isolated subcranial access without face incisions was employed in 6 cases. The average surgical time was of 8.38h. The average stay in the intensive care unit was 1.2 days and the hospitalization time was 7.8 days. We did not observe immediate neurological complications. The complications incidence was 28.5%, without surgical death. The overall survival rate was 61.9% for malignant tumors. Conclusion: this is an innovative surgical approach in which we could observe some notables benefits, such as the reduction of neurological and general complications, trend to reduce to reduce the surgical time, low tax of hemotransfusion, minor time of stay under intensive care and in the hospital, and practicability for facial tumors resection, involving the cribriform plate or small invasion of the anterior skull base.

Formação expansiva mediastinal após angioplastia percutânea / Mediastinal mass after percutaneous transluminal coronary angioplasty

A descrição de relatos de caso tem o objetivo de mostraro os números diagnósticos possíveis numa determinada situação clínica, bem como o raciocínio e os métodos de investigação que foram utilizados pela equipe médica envolvida. Será discutido o diagnóstico de formação expansiva mediastinal que surgiu após angioplastia percutânea.