Standardized PSMA-PET Imaging of Advanced Prostate Cancer.

Imaging of advanced prostate cancer is a challenging task, as it requires longitudinal characterization of disease extent in a standardized way to enable appropriate treatment selection and evaluation of treatment efficacy. In the last years, prostate-specific membrane antigen (PSMA)-PET/CT has become the reference standard examination for patients with advanced prostate cancer. Together with the rise of PSMA-PET, standardized frameworks for the reporting of image findings have been proposed, eg, the Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) and the structured reporting system for PSMA targeted PET imaging (PSMA-RADS) framework. Therefore, recent evidence on PSMA-PET derived tumor volume as useful a biomarker for outcome prognostication and related frameworks will be discussed in the article. The PROMISE framework recommends quantifying the tumor volume per-organ system, which accounts for the fact that the location of the metastases greatly influence its biological aggressiveness. In addition, changes in PSMA-PET derived tumor volume have been shown to be promising biomarkers for response assessment. Limitations of PSMA-PET will also be discussed because the tumor volume might not always be suited for response assessment. As a pitfall of PSMA-based systems, decreasing PSMA-expression might erroneously be interpreted as response to therapy. Also, especially for patients with limited disease, the tumor volume might not be ideal for response assessment. Therefore, various frameworks have been introduced to objectively measure response to therapy with PSMA-PET. Amongst these, the PSMA-PET progression (PPP) criteria and the response evaluation criteria in PSMA (RECIP) are optimized for earlier and later phenotypes of advanced prostate cancer, respectively. Variables needed to determine PPP or RECIP outcome on PSMA-PET are recorded under the umbrella of PROMISE recommendations. In this article, various reporting and response assessment frameworks are explained and discussed. Also, recent evidence for the relevance of PSMA-PET biomarkers for clinical management and outcome prognostication are shown.

Valor predictivo de los índices 18F-FDG PET/TC sobre la carga tumoral residual en pacientes con cáncer de mama extenso tratadas con quimioterapia neoadyuvante / Predictive value of 18F-FDG PET/CT indices on extensive residual cancer burden in breast cancer patients treated with neoadjuvant chemotherapy

Objetivo: Investigamos la correlación entre los índices de PET/TC con 18F-FDG y la respuesta patológica en el cáncer de mama tratado con quimioterapia neoadyuvante (QNA), que se puntuó con el sistema de carga de cáncer residual (RCB) después de la cirugía. Nuestro objetivo es detectar antes una carga extensa de cáncer residual mediante el uso de los índices de PET/TC. Métodos: Se recuperaron las características de las pacientes de forma retrospectiva. Se calculó el valor máximo de captación estándar (SUVmáx), el volumen metabólico del tumor (MTV) y los índices de glucólisis total de la lesión (TLG), así como la tasa de reducción (RR) entre la línea de base y la evaluación intermedia, con la exploración FDG PET/TC. Todos los pacientes fueron evaluados según las puntuaciones RCB después de la cirugía. Las respuestas patológicas y los resultados de las mediciones de PET/TC se analizaron con parámetros demográficos y clínicos. Resultados: Un total de 95 pacientes fueron incluidos en el estudio. Según las respuestas patológicas, la distribución de RCB-0, -1, -2, -3 fue de 13 (13,7%), 11 (11,6%), 30 (31,6%) y 41 (43,2%), respectivamente. La supervivencia libre de enfermedad fue significativamente menor en el grupo RCB-3 en comparación con el grupo de respuesta patológica (p=0,01). Según el análisis multivariante, se determinó que el RR del SUVmáx era una variable independiente que predecía la RCB extensa con un valor de corte óptimo del 86% (p<0,05). Conclusiones: Determinamos el RR de SUVmáx como un factor independiente para predecir la carga tumoral residual extensa. Creemos que el RR de SUVmáx es suficiente para predecir la respuesta patológica en la práctica diaria. Además, las mediciones de MTV y TLG no contribuyen adicionalmente al SUVmáx por sí solas y pueden causar una pérdida de trabajo innecesaria (AU)

Aim: We investigated the correlation between 18F-FDG PET/CT indices and pathological response in breast cancer treated with neoadjuvant chemotherapy (NACT) which was scored with Residual Cancer Burden (RCB) system after surgery. Our aim is to detect extensive residual cancer burden earlier by using PET/CT indices. Methods: Characteristics of patients were retrieved retrospectively. Baseline maximum Standart Uptake Value (SUVmax), Metabolic Tumor Volume (MTV) and Total Lesion Glycolysis (TLG) indices and reduction rate (RR) between baseline and interim evaluation were calculated with FDG PET/CT scan. All patients were evaluated according to RCB scores after surgery. Pathological responses and PET/CT measurement results were analyzed with demographic and clinical parameters. Results: A total of 95 patients were included in the study. According to pathological responses, the distribution of RCB-0, -1, -2, -3 were 13 (13.7%), 11 (11.6%), 30 (31.6%), 41 (43.2%), respectively. Disease-free survival was significantly lower in the RCB-3 group compared to the pathological responder group (P=.01). According to multivariate analysis, RR of SUVmax was determined as an independent variable predicting extensive residual cancer burden with an optimal cut-off value of 86% (P<.05). Conclusions: We determined RR of SUVmax as an independent factor for predicting extensive residual tumor burden. We believe that RR of SUVmax is sufficient to predict pathological response in daily practice. In addition, MTV and TLG measurements do not contribute additionally to SUVmax alone and can cause unnecessary labor loss (AU)

Adjuvant chemotherapy for rectal cancer: Current evidence and recommendations for clinical practice.

While adjuvant chemotherapy is an established treatment for pathological stage II and especially stage III colon cancer, its role in the multimodal management of rectal cancer remains controversial. As a result, there is substantial variation in the use of this treatment in clinical practice. Even among centres and physicians who consider adjuvant chemotherapy as a standard treatment, notable heterogeneity exists with regard to patient selection criteria and chemotherapy regimens. The controversy around this topic is confirmed by the lack of full consensus among national and international clinical guidelines. While most of the clinical trials do not support the contention that adjuvant chemotherapy may improve survival outcomes if pre-operative (chemo)radiotherapy is also given, these suffer from many limitations that preclude drawing definitive conclusions. Nevertheless, in the era of evidence-based medicine, physicians should be guided by the available data and refrain from extrapolating results of adjuvant colon cancer trials to inform treatment decisions for rectal cancer. Patients should be informed of the evidence gap, be given the opportunity to carefully discuss pros and cons of all the possible management options and be empowered in the decision making. In this article we review the available evidence on adjuvant chemotherapy for rectal cancer and propose a risk-adapted decisional algorithm that largely relies on informed patient preferences.

Evaluation of the frequency of left renal vein variations in computed tomography and its relationship with cancer development.

BACKGROUND: Left renal vein (LRV) variations occur in 0.8-10.2% of the population. The most common LRV variations are retroaortic left renal vein (RLRV) and circumaortic left renal vein (CLRV). The purpose of this study is to determine the frequency of LRV variations in a large series on computed tomography (CT) and to investigate the association between LRV and malignancy development. MATERIALS AND METHODS: Between January 2015 and January 2017, an abdominal CT examination of 12,341 (5505 female, 6836 male) patients was evaluated retrospectively in this study. Patients' clinical and demographic data were recorded using the Hospital Information System. RESULTS: Left renal vein variations were detected in 314 (2.54%) of the 12,341 patients within the study. Of the 314 cases found to have LRV variations, 227 (1.84%) had RLRV, and 87 (0.70%) had CLRV. There was no statistical difference in total LRV variations (p = 0.083) and CLRV variation (p = 0.96) groups in terms of gender. However, the RLRV variation was found to be 1.32 times higher in males than in females (p = 0.039). Of the 314 patients with LRV variations, 73 (23.2%) had any sort of concomitant malignancy. CONCLUSIONS: A high incidence of malignancy was detected in patients with LRV variations. Of the LRV variations, RLRV variation is more common than CLRV variation. The presence of total LRV variations and CLRV variations is not associated with gender; whereas the presence of RLRV variation is more common in males.

Grey areas and evidence gaps in the management of rectal cancer as revealed by comparing recommendations from clinical guidelines.

BACKGROUND: While the management of nonmetastatic and oligometastatic rectal cancer has rapidly evolved over the last few decades, many grey areas and highly debated topics remain that foster significant variation in clinical practice. We aimed to identify controversial points and evidence gaps in this disease setting by systematically comparing recommendations from national and international clinical guidelines. METHODS: Twenty-six clinical questions reflecting practical challenges in the routine management of nonmetastatic and oligometastatic rectal cancer patients were selected. Recommendations from the ESMO, NCCN, JSCCR, Australian and Ontario guidelines were extrapolated and compared using a 4-tier classification system (i.e., identical/very similar, similar, slightly different, different). Overall agreement between guidelines (i.e., substantial/complete disagreement, partial disagreement, partial agreement, substantial/complete agreement) was assessed for each clinical question and compared against the highest level of available evidence by using the χ2 statistic test. RESULTS: Guidelines were in substantial/complete agreement, partial agreement, partial disagreement, and substantial/complete disagreement for 8 (30.8%), 2 (7.7%), 7 (26.9%), and 9 (34.6%) clinical questions, respectively. High level of evidence supported clinical recommendations in 3/10 cases (30%) where guidelines were in agreement and in 10/16 cases (62.5%) where guidelines were in disagreement (χ2 = 2.6, p = 0.106). Agreement was frequently reached for questions regarding diagnosis, staging, and radiology/pathology pro-forma reporting, while disagreement characterised most of the treatment-related topics. CONCLUSIONS: Substantial variation exists across clinical guidelines in the recommendations for the management of nonmetastatic and oligometastatic rectal cancer. This variation is only partly explained by the lack of supporting, high-level evidence.

Effect of PET/CT standardized uptake values on complete response to treatment before definitive chemoradiotherapy in stage III non-small cell lung cancer.

PURPOSE: The standard treatment for patients with stage III non-small cell lung cancer (NSCLC), unsuitable for resection and with good performance, is definitive radiotherapy with cisplatin-based chemotherapy. Our aim is to evaluate the effect of the maximum value of standardized uptake values (SUVmax) of the primary tumor in positron emission tomography-computed tomography (PET/CT) before treatment on complete response (CR) and overall survival. METHODS: The data of 73 stage III NSCLC patients treated with concurrent definitive chemoradiotherapy (CRT) between 2008 and 2017 and had PET/CT staging in the pretreatment period were evaluated. ROC curve analysis was performed to determine the ideal cut-off value of pretreatment SUVmax to predict CR. RESULTS: Median age was 58 years (range 27-83 years) and 66 patients were male (90.4%). Median follow-up time was 18 months (range 3-98 months); median survival was 23 months. 1-year overall survival (OS) rate and 5-year OS rate were 72 and 19%, respectively. Median progression-free survival (PFS) was 9 months; 1-year PFS rate and 5-year PFS rate were 38 and 19%, respectively. The ideal cut-off value of pretreatment SUVmax that predicted the complete response of CRT was 12 in the ROC analysis [AUC 0.699 (0.550-0.833)/P < 0.01] with a sensitivity of 83%, and specificity of 55%. In patients with SUVmax < 12, CR rate was 60%, while, in patients with SUV ≥ 12, it was only 19% (P = 0.002). Median OS was 26 months in patients with pretreatment SUVmax < 12, and 21 months in patients with SUVmax ≥ 12 (HR = 2.93; 95% CI 17.24-28.75; P = 0.087). CR rate of the whole patient population was 26%, and it was the only factor that showed a significant benefit on survival in both univariate and multivariate analyses. CONCLUSION: Pretreatment SUVmax of the primary tumor in PET/CT may predict CR in stage III NSCLC patients who were treated with definitive CRT. Having clinical CR is the only positive predictive factor for prolonged survival.

Valor de las imágenes de 177Lu-PSMA post-terapia para una interpretación precisa de la respuesta a la terapia con PET/TC con 68Ga-PSMA / Value of post-therapy 177Lu-PSMA images for accurate interpretation of therapy response with 68Ga-PSMA PET/CT

Paciente de 54 años de edad con cáncer de próstata al que se realizó estudio PET/TC con 68Ga-PSMA que mostró afectación linfática y metástasis óseas. Después de 2 ciclos de tratamiento con 177Lu-PSMA, una nueva PET/TC mostró disminución de la captación en los ganglios linfáticos y las lesiones óseas, pero aparecieron nuevas lesiones compatibles con progresión de la enfermedad o efecto llamarada. La revisión de las imágenes de 177Lu-PSMA mostró que las nuevas lesiones de la segunda PET/TC correspondían a lesiones metastásicas que captaban más que en la primera PET/TC y que posteriormente presentaron buena respuesta. El paciente recibió ciclos adicionales de tratamiento con 177Lu-PSMA con regresión de la enfermedad, alcanzando niveles de PSA de 0,06ng/ml. La evaluación de la respuesta de los nuevos agentes «teragnósticos» precisa realizar una revisión no solo de las imágenes diagnósticas de la PET/TC sino también de las imágenes posterapia y los datos de laboratorio (AU)

A 54-year-old man with progressive prostate cancer underwent a 68Ga-PSMA PET/CT, which showed lymph node and bone metastases. After 2-cycles of 177Lu-PSMA therapy, the repeated 68Ga-PSMA PET/CT showed decreased radiotracer uptake in lymph node and bones metastases, but there were new lesions which may be compatible with progression or tumour sink-effect. A review of 177Lu-PSMA-therapy images revealed that new lesions in the second PET/CT were the metastatic lesions that progressed after the first PET/CT, and subsequently showed a good response. The patient received additional cycles of 177Lu-PSMA therapy, and the disease regressed further, with a PSA of 0.06ng/ml. Response evaluation of new therapeutic diagnostics (theranostic) agents needs a review of not only diagnostic PET/CT images, but also post-therapy images and laboratory results (AU)

Value of post-therapy 177Lu-PSMA images for accurate interpretation of therapy response with 68Ga-PSMA PET/CT. / Valor de las imágenes de 177Lu-PSMA post-terapia para una interpretación precisa de la respuesta a la terapia con PET/TC con 68Ga-PSMA.

A 54-year-old man with progressive prostate cancer underwent a 68Ga-PSMA PET/CT, which showed lymph node and bone metastases. After 2-cycles of 177Lu-PSMA therapy, the repeated 68Ga-PSMA PET/CT showed decreased radiotracer uptake in lymph node and bones metastases, but there were new lesions which may be compatible with progression or tumour sink-effect. A review of 177Lu-PSMA-therapy images revealed that new lesions in the second PET/CT were the metastatic lesions that progressed after the first PET/CT, and subsequently showed a good response. The patient received additional cycles of 177Lu-PSMA therapy, and the disease regressed further, with a PSA of 0.06ng/ml. Response evaluation of new therapeutic diagnostics (theranostic) agents needs a review of not only diagnostic PET/CT images, but also post-therapy images and laboratory results.