Immunotherapy, cancer and PET. / Inmunoterapia, cáncer y PET.

The treatment of cancer by immunotherapy has been a revolution, as it is the first strategy that manages to control the disease for prolonged periods of time. Its efficacy is associated with different imaging response patterns and the appearance of new toxicities. We would highlight two patterns of tumour response: pseudoprogression, or growth of tumour lesions after the start of immunotherapy treatment, followed by a significant reduction in lesions, and hyperprogression, acceleration of tumour progression and metastasis early after the start of treatment. The emergence of such patterns has generated new metabolic response criteria, such as PECRIT, PERCIMT, imPERCIST and IPERCIST. Of particular interest are the new immunoPET-specific biomarkers, as they allow the identification of patients presenting the tumour target and are useful for predicting response to immunotherapy.

Diagnostic accuracy of visual analysis versus dual time-point imaging with 18F-FDG PET/CT for the characterization of indeterminate pulmonary nodules with low uptake. / Precisión diagnóstica del análisis visual frente al protocolo de imagen tardía con 18F-FDG PET/TC para la caracterización de nódulos pulmonares indeterminados con baja captación.

OBJECTIVE: To determine the accuracy of visual analysis and the retention index (RI) with dual-time point 18F-FDG PET/CT for the characterization of indeterminate pulmonary nodules (IPN) with low FDG uptake. MATERIALS AND METHODS: A retrospective analysis was performed on 43 patients (28 men, 64 ± 11 years old, range 36-83 years) referred for IPN characterization with 18F-FDG-PET/CT and maximum standard uptake value ≤ 2.5 at 60 minutes post-injection (SUVmax1). Nodules were analyzed by size, visual score for FDG uptake on standard (OSEM 2,8) and high definition (HD) reconstructions, SUVmax1, SUVmax at 180 minutes post-injection (SUVmax2), and RI was calculated. The definitive diagnosis was based on histopathological confirmation (n = 28) or ≥ 2 years of follow-up. RESULTS: Twenty-four (56%) nodules were malignant. RI ≥ 10% on standard reconstruction detected 18 nodules that would have been considered negative using the standard SUVmax ≥ 2.5 criterion for malignancy. RI ≥ 10% had a sensitivity, specificity, PPV, NPV and accuracy of 75, 73.7, 78.3, 70, and 74.4%, respectively, while for FDG uptake > liver on HD these were 79.1, 63.2, 73.1, 70.6, and 72.1%, respectively. SUVmax1 ≥ 2, SUVmax2 > 2.5 and FDG uptake > liver on standard reconstruction had a PPV of 100%. FDG uptake > mediastinum on HD had a NPV of 100%. CONCLUSIONS: RI ≥ 10% was the most accurate criterion for malignancy, followed by FDG uptake > liver on HD reconstruction. On standard reconstruction, SUVmax1 ≥2 was highly predictive of malignancy, as well as SUVmax2 > 2.5 and FDG uptake > liver. FDG uptake < mediastinum on HD was highly predictive of benign nodules.

A multidisciplinary consensus on the morphological and functional responses to immunotherapy treatment.

The implementation of immunotherapy has radically changed the treatment of oncological patients. Currently, immunotherapy is indicated in the treatment of patients with head and neck tumors, melanoma, lung cancer, bladder tumors, colon cancer, cervical cancer, breast cancer, Merkel cell carcinoma, liver cancer, leukemia and lymphomas. However, its efficacy is restricted to a limited number of cases. The challenge is, therefore, to identify which subset of patients would benefit from immunotherapy. To this end, the establishment of immunotherapy response criteria and predictive and prognostic biomarkers is of paramount interest. In this report, a group of experts of the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) provide an up-to-date review and a consensus guide on these issues.

FDG PET/CT in colorectal cancer. / FDG PET/TC en el cáncer colorrectal.

Colorectal cancer is the third most frequent cancer worldwide. Although its incidence is increasing, mainly in those aged under50, mortality has decreased by 50% in the more developed countries, principally due to the adoption of new practices in prevention, diagnosis and treatment. In particular, the various diagnostic imaging modalities allow improved therapeutic decision-making, evaluation of the response and early detection of recurrence. The aim of this paper is to review the available scientific evidence on the value of positron emission tomography with 18F-FDG (18F-FDG PET/CT) in the colorectal cancer, with special emphasis on the indications of the guidelines and recommendations of the main international scientific associations regarding this imaging technique.

Association between [18F]fluorodeoxyglucose uptake and prognostic parameters in breast cancer.

BACKGROUND: This study analysed the correlation between [(18)F]fluorodeoxyglucose (FDG) uptake assessed by positron emission tomography (PET) in breast tumours, and histopathological and inmunohistochemical prognostic factors. METHODS: FDG-PET was performed before surgery in 275 women with primary breast cancer. The standarized uptake value (SUV) was compared with histopathological findings after surgery. RESULTS: A positive relationship was found between the SUV and tumour size (r = 0.46, P < 0.001), axillary lymph node status (P < 0.001), histological type (P < 0.001), histological grade (P < 0.001), oestrogen receptor status (P < 0.001), p53 (P < 0.001) and Ki-67 (P < 0.001) expression. Multivariable linear regression showed that tumour size, histological grade, Ki-67 expression, oestrogen receptor status and histological type were significantly related to the SUV. CONCLUSION: The SUV is a preoperative and non-invasive metabolic factor that relates to some prognostic factors in breast cancer.

18F-FDG PET/CT in locally advanced cervical cancer: A review. / PET/TC con 18F-FDG en cáncer de cérvix localmente avanzado.

Cervical cancer is the second most common gynecological cancer worldwide. In locally advanced cervical cancer, 18F-FDG PET/CT has become important in the initial staging, particularly in the detection of nodal and distant metastasis, aspects with treatment implications and prognostic value. The aims of this study were to review the role of 18F-FDG PET/CT in uterine cervical cancer, according to the guidelines of the main scientific institutions (FIGO, NCCN, SEGO, SEOM, ESGO, and ESMO) and its diagnostic accuracy compared to conventional radiological techniques, as well as to review the acquisition protocol and its utility in radiotherapy planning, response assessment and detection of recurrence.

[Positron emission tomography in breast cancer]. / Tomografía por emisión de positrones en el cáncer de mama.

PET18FDG is an imaging diagnostic technique that shows changes in glycolitic metabolism that appear at a very early phases in the tumoral process. The main limitation of PET in breast cancer is the detection of small tumor lesions and axillary micrometastases. However it offers important information in the staging of high risk patients, in clinical relapse or in therapeutic evaluation. The new PET-CT devices offer advantages over conventional techniques. It provides a greater precision in the localization of tumoral foci. In spite of current difficulties for clinical applications, fluoro-estradiol (18F-ES) offers the possibilty of studying the presence of estrogenic receptors both in the primary and in the metastases. It may prove to be a useful tool to obtain information about therapeutic management and prognosis of breast cancer.

Radium-223 in the treatment of bone metastasis in patients with castration-resistant prostate cancer. Review and procedure. / Radio-223 en el tratamiento de metástasis óseas en pacientes con cáncer de próstata resistente a la castración. Revisión de la literatura y procedimiento.

Bone metastatic disease is the main cause of morbidity / mortality in patients with prostate cancer, presenting frequently as bone pain, pathological fractures or spinal cord compression, which requires early and timely therapy. Although, for the moment, the therapeutic window for its use has not been definitively established, radium-223 (223Ra), an alpha particle emitter, has proved to be an effective therapeutic tool, pre or post-chemotherapy, in patients with castration-resistant prostate cancer with symptomatic bone metastases and absence of visceral metastases, significantly modifying the prognosis of the disease. It is therefore imperative to define the ideal scenarios and the correct protocol for the use of this therapy and thus offer the greatest possible clinical benefit to the patient.

68Ga-PSMA PET/CT in prostate cancer. / La PET/TC con 68Ga-PSMA en el cáncer de próstata.

Positron emission tomography/computed tomography (PET/CT) with 68Ga-PSMA is a non-invasive diagnostic technique to image prostate cancer with increased prostate-specific membrane antigen (PSMA) expression. PSMA is a transmembrane protein present in all prostatic tissues. Increased PSMA expression is seen in several malignancies, although prostate cancer is the tumour where it presents higher concentrations. Almost all prostate adenocarcinomas show PSMA expression in most of lesions, primary and metastatic. Immunohistochemistry has demonstrated that the expression of PSMA increases in patients with de-differentiated, metastatic or hormone-refractory tumours. Moreover, the expression level of PSMA has a prognostic value for disease outcome. PET measures the three-dimensional distribution of 68Ga-PSMA, producing semi-quantitative images that allow for non-invasive assessment of PSMA expression.

18F-FDG metabolism in a rat model of chronic infarction: a 17-sector semiquantitative analysis.

UNLABELLED: Strategies to establish the functional benefit of cell therapy in cardiac regeneration and the potential mechanism are needed. AIMS: Development of a semi-quantitative method for non invasive assessment of cardiac viability and function in a rat model of myocardial infarction (MI) based on the use of microPET. ANIMALS, METHODS: Ten rats were subjected to myocardial imaging 2, 7, 14, 30, 60 and 90 days after left coronary artery ligation. Intravenous 18F-fluoro-2-deoxy-2-D-glucose (18F-FDG) was administered and regional 18F activity concentrations per unit area were measured in 17 regions of interest (ROIs) drawn on cardiac polar maps. By comparing the differences in 18F uptake between baseline and each of the follow up time points, parametric polar maps of statistical significance (PPMSS) were calculated. Left ventricular ejection fraction (LVEF) was blindly assessed echocardiographically. All animals were sacrificed for histopathological analysis after 90 days. RESULTS: The diagnostic quality of 18F-FDG microPET images was excellent. PPMSS demonstrated a statistically significant decrease in 18F concentrations as early as 48 hours after MI in 4 of the 17 ROIs (segments 7, 13, 16 and 17; p < 0.05) that persisted throughout the study. Semiquantitative analysis of 18F-FDG uptake correlated with echocardiographic decrease in LVEF (p < 0.001). CONCLUSION: The use of PPMSS based on 18F-FDG-microPET provides valuable semi-quantitative information of heart glucose metabolism allowing for non-invasive follow up thus representing a useful strategy for assessment of novel therapies in cardiac regeneration.

A multidisciplinary consensus on the morphological and functional responses to immunotherapy treatment

The implementation of immunotherapy has radically changed the treatment of oncological patients. Currently, immunotherapy is indicated in the treatment of patients with head and neck tumors, melanoma, lung cancer, bladder tumors, colon cancer, cervical cancer, breast cancer, Merkel cell carcinoma, liver cancer, leukemia and lymphomas. However, its efficacy is restricted to a limited number of cases. The challenge is, therefore, to identify which subset of patients would benefit from immunotherapy. To this end, the establishment of immunotherapy response criteria and predictive and prognostic biomarkers is of paramount interest. In this report, a group of experts of the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) provide an up-to-date review and a consensus guide on these issues (AU)

[Imaging modalities in cardiology: the present answers to permanent questions]. / Las técnicas de imagen en cardiología: la respuesta actual a los interrogantes de siempre.

Tremendous advances have been made in non-invasive cardiology, such as improved visualization of the anatomy and function of the heart and better understanding of heart disease. Echocardiography has improved in both simplicity and complexity, offering a range of modalities from small, hand-held devices that provide basic information simply and inexpensively to complex, dynamic three-dimensional imaging of regional myocardial function. Cardiovascular magnetic resonance imaging is the newest technique for non-invasive cardiology. It assesses cardiac function, mass and volume and can detect myocardial infarction, fibrosis, valvular and congenital heart disease. Computed tomography is used to detect and quantify coronary heart disease and coronary calcium, high scores being related to increased risk, but its use remains controversial. Myocardial perfusion scintigraphy single photon emission computed tomography (SPECT) is cost effective in investigating patients with suspected coronary disease and acute coronary syndrome. Also positron emission tomography (PET) is useful in the study of perfusion, metabolism, patients selection for revascularization, and in translational research in transgenic animal models.

Impact of initial FDG PET/CT in the management plan of patients with locally advanced head and neck cancer.

OBJECTIVE: To determine the impact of initial FDG PET/CT staging on clinical stage and the management plan in patients with locally advanced head and neck cancer (LAHNC). MATERIALS AND METHODS: We retrospectively reviewed the records of 72 consecutive patients (2007-2010) staged with PET/CT and conventional CT with tumours of hypopharynx/larynx (26 patients, 36 %), oral cavity (17 patients, 24 %), oropharynx (16 patients, 22 %), nasopharynx (12 patients, 17 %), and others (2 %). The impact of PET/CT on management plans was considered high when PET/CT changed the planned treatment modality or treatment intent, and intramodality changes were considered as minor changes with low impact. RESULTS: FDG PET/CT changed the stage in 27 patients and had high impact on the management plan in 12 % of patients (detection of distant metastases in 6 patients and stage II in 2 patients). Intramodality changes were more frequent: FDG PET/CT altered the TNM stage in 18/72 (25 %) of patients, upstaging N stage in 90 % of patients with low impact. CONCLUSIONS: Initial FDG PET/CT staging not only improves stage but also affects the management plan in LAHNC patients.

Three-dimensional clinical PET in lung cancer: validation and practical strategies.

UNLABELLED: The feasibility of 3-dimensional acquisition mode for semiquantitative analysis in thoracic PET studies was compared to the conventional 2-dimensional mode. Several practical considerations were analyzed to propose an optimized scanning protocol for clinical use. METHODS: Twenty-one patients with focal thoracic abnormalities were evaluated with FDG PET. The acquisition consisted of 3 consecutive static scans for a single bed position: 3-dimensional (10 min), 2-dimensional (15 min), and 3-dimensional (5 min). On the basis of the average and maximum activity values per region of interest, standardized uptake value (SUV) normalized for total body weight (TBW), lean body mass (LBM), body surface area (BSA), and blood glucose level (PGL) were evaluated. The effect of the delay between tracer injection and PET scanning on the SUV, as well as on the relative error of the activity distribution, was studied from 40-134 min after tracer injection. RESULTS: A strong positive correlation was observed among SUVs from 2-dimensional and both 3-dimensional acquisitions. The mean SUV percentage differences between both acquisition modes were about 17%, differences that were not statistically significant when time postinjection was addressed in the analysis of covariance. SUVs provided the greatest variability and differences among studies on experimental periods up to 70 min postinjection. Indeed, the variability of 20% observed on the SUVs from 2 PET scans 13 min apart was reduced to 9% when the acquisitions started at least 70 min after tracer injection. In addition, a two-fold reduction in the relative error of the activity distribution was observed over this period of time. The reproducibility coefficient was increased from 0.87 to 0.95 before and after 70 min postinjection, respectively. No correlation was found between different normalization procedures of SUV and LBM, BSA, TBW, or height, whereas a weak correlation was found between SUV and PGL. CONCLUSION: 18F-FDG 3-dimensional PET is a realistic alternative to the gold standard 2-dimensional for clinical nonkinetic studies. A short, 5-min 3-dimensional acquisition at 70 min postinjection is proposed as the best protocol for the clinical evaluation of thoracic pathologies.

18F-FDG PET complemented with sentinel lymph node biopsy in the detection of axillary involvement in breast cancer.

AIM: The presence of axillary involvement is the most important prognostic factor in breast cancer. This study analysis the value of 18F-FDG PET in the detection of the lymph node status. METHODS: This study includes 200 breast cancer patients. The PET scans were obtained after the injection of 370 MBq of 18F-FDG; the breast areas, axillary, supraclavicular and internal mammary lymph node chains were evaluated. In a subgroup of 100 patients the PET-FDG scan was complemented with the study of the sentinel node (SN) in those cases which did not demonstrate pathological lymph node uptake. The standardized uptake value (SUV) was related to the tumour characteristics of size, histological type, axillary status and histological grading. RESULTS: The sensitivity and specificity of PET-FDG in the detection of axillary involvement was 84.1 and 97.8%, respectively. Seventeen false negative cases were obtained, and were associated with low SUV in the mammary tumour. In 15 cases the PET-FDG scans revealed pathological uptake foci that suggested involvement of the internal mammary chain. CONCLUSIONS: The PET-FDG avoids routine SN study in those cases presenting axillary uptake, but it must be complemented by sentinel node study in those cases without pathological uptake. The association of PET-FDG and SN improves the sensitivity in the detection of axillary involvement. Its sensitivity and specificity in the analysis of axillary status can be extended to the evaluation of the internal mammary chain.

Clandestine ischemia in patients with vasospastic angina.

BACKGROUND: Coronary vasospasms generally occur at rest, but can also be triggered by physical exercise. Anginal pain and ST-segment elevation may be seen during exercise-stress tests. ST-segment depression, due to nonocclusive vasospasms, has also been found to occur. When the result of a test is positive, scintigraphy usually reveals perfusion defects. True silent or clandestine ischemia (normal result of exercise test with perfusion defects) in these patients is very uncommon. OBJECTIVE: To stress the need for suspecting occurrence of coronary vasospasms in order to perform a proper diagnosis. METHODS: Eight patients with angina were selected for this study. They had negative results of exercise tests with perfusion defects detected by thallium-201 tomography, normal coronary arteries and vasospasms. Maximal exercise-stress tests with thallium-201 tomography were performed. Sizes of perfusion defects were quantified by examining polar maps. Coronary angiography and then an intracoronary ergonovine test were performed for each patient. RESULTS: Significant defects were seen in territory of the right coronary artery, the left anterior descending artery, or both. Lung:heart ratio was normal in every case. The coronary arteries were normal and vasospasms were elicited with ergonovine in all the patients. Correspondence between the location of perfusion defects and angiographic spasms was generally observed. After treatment with calcium antagonists and nitrates all of them improved and defects detected by thallium tomography were no longer found when tests were repeated. CONCLUSIONS: Some patients with vasospastic angina may have normal results of exercise-stress tests and reversible perfusion defects detectable by scintigraphy. This finding must lead one to perform coronary angiography without administration of nitroglycerine beforehand and an ergonovine test if the coronary arteries are normal.

FDG-PET detection of primary lung cancer in a patient with an isolated cerebral metastasis.

Positron emission tomography (PET) is a new diagnostic technique. It is used to differentiate benign from malignant pulmonary nodules and to detect metastasis and lymph node involvement in primary lung cancer, but little has been published about its possible interest for detection of unknown primary tumors. We report the case of a man who underwent resection of a cerebral tumor. A histological diagnosis of cerebral metastasis from adenocarcinoma with a probable pulmonary origin was made. Preoperative staging (including thoracoabdominal CT-scan and bone scan) did not show any pathologic image, particularly in the thorax. A whole body FDG-PET-scan was then performed. An isolated (1.5 cm of diameter) hypermetabolic focus was discovered in the left upper lobe. Bronchoscopy was normal An upper left lobectomy confirmed the presence of the primary lung adenocarcinoma. In this particular case, FDG-PET proved to be a very useful diagnostic method. New indications are being developed for it.

[Clinical usefulness of positron emission tomography (PET) in the evaluation of myocardial viability]. / Utilidad clínica de la tomografía de emisión de positrones (PET) en la valoración de la viabilidad miocárdica.

Positron emission tomography (PET) is a radionuclide imaging technique that allows quantitative assessment of regional myocardial function. It is mainly used in clinics to assess viability of dissynergic myocardium, by means of combined images of flow (with ammonia) and metabolism (with fluordeoxyglucose). The mismatch pattern, with an increase in fluordeoxyglucose metabolism in hypoperfused regions, is indicative of viability. The match pattern (a decrease in flow and metabolism in the same areas) is indicative of necrosis. Viability can also be assessed with water or fluordeoxyglucose independently quantified. Other promising methods are based in the study of oxygen consumption with 11C acetate and the study of hypoxia with 18F-misonidazole.