The predictive role of interim PET after the first chemotherapy cycle and sequential evaluation of response to ABVD in Hodgkin's lymphoma patients-the Polish Lymphoma Research Group (PLRG) Observational Study.

BACKGROUND: Interim PET after two ABVD cycles (iPET2) predicts treatment outcome in classical Hodgkin's lymphoma. To test whether an earlier assessment of chemosensitivity would improve the prediction accuracy, we launched a prospective, multicenter observational study aimed at assessing the predictive value of iPET after one ABVD (iPET1) and the kinetics of response assessed by sequential PET scanning. PATIENTS AND METHODS: Consecutive patients with newly diagnosed classical Hodgkin's lymphoma underwent interim PET scan after one ABVD course (iPET1). PETs were interpreted according to the Deauville score (DS) as negative (-) (DS 1-3) and positive (+) (DS 4, 5). Patients with iPET1 DS 3-5 underwent iPET2. RESULTS: About 106 early (I-IIA) and 204 advanced (IIB-IV) patients were enrolled between January 2008 and October 2014. iPET1 was (-) in 87/106 (82%) or (+) in 19/106 (18%) of early, and (-) in 133/204 (65%) or (+) in 71/204 (35%) of advanced stage patients, respectively. Twenty-four patients were excluded from response analysis due to treatment escalation. After a median follow-up of 38.2 (3.2-90.2) months, 9/102 (9%) early and 43/184 (23%) advanced patients experienced a progression-free survival event. At 36 months, negative and positive predictive value for iPET1 were 94% and 41% (early) and 84% and 43% (advanced), respectively. The kinetics of PET response was assessed in 198 patients with both iPETs. All 116 patients with iPET1(-) remained iPET2(-) (fast responders), 41/82 with IPET1(+) became iPET2(-) (slow responders), and the remaining 41 stayed iPET2(+) (non-responders); progression-free survival at 36 months for fast, slow and non-responders was 0.88, 0.79 and 0.34, respectively. CONCLUSION: The optimal tool to predict ABVD outcome in HL remains iPET2 because it distinguishes responders, whatever their time to response, from non-responders. However, iPET1 identified fast responders with the best outcome and might guide early treatment de-escalation in both early and advanced-stage HL.

Role of 18FDG-PET/CT in detecting relapse during follow-up of patients with Hodgkin's lymphoma.

The role of 18FDG-PET/CT during follow-up of patients affected by Hodgkin's lymphoma (HL) in complete remission after treatment is not fully elucidated, since a wide use of 18F fluorodeoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) in this setting could be limited by a relative high rate of false-positive results. Herein, we summarize a retrospective analysis of 27 patients with Hodgkin's lymphoma in complete remission after the first-line (n = 20) or salvage (n = 7) therapy receiving serial 18FDG-PET/CT scans during follow-up. Out of 165 scans, 13 were suspected for relapse, which was confirmed in seven patients. All relapses were correctly identified by 18FDG-PET/CT positivity, with a 100% sensitivity; false-positive rate was 46% and negative predictive value was 100%. True-positive findings were mostly associated with multiple sites, subdiaphragmatic involvement, and/or previous sites of disease. According to our results, we conclude that performing routine PET/CT scan during follow-up of those patients who are at high risk of relapse would be advisable, although caution must be adopted when interpreting PET/CT results due to the relatively high rate of false-positive findings. If FDG abnormal uptake is present at multiple nodal sites, subdiaphragmatic lymph nodes, or previous sites of disease, histological verification of PET abnormal findings is warranted.

Prognostic role of FDG PET-derived parameters in preoperative staging of endometrial cancer. / Función pronóstica de los parámetros derivados de FDG PET en la estadificación preoperatoria del cáncer de endometrio.

PURPOSE: To investigate the preoperative prognostic role of 18F-FDG PET/CT in patients with endometrial carcinoma (EC). METHODS: 18F-FDG PET/CT was performed in 57 patients for EC preoperative staging. Maximum and mean standardized uptake values (SUVmax, mean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of primary tumors, at different thresholds of 40%, 50%, 60% (40-50-60), were evaluated and compared with anatomopathological features. The diagnostic performance of PET-parameters (categorized by ROC analysis) in discriminating low-intermediate and high-risk disease and the prognostic role on survival (overall survival -OS; disease free survival - DFS) was evaluated. RESULTS: The categorized TLG40-50-60 were the only parameters related to FIGO stage I versus II-III-IV (p = 0.0035 for all). The cut-off values for risk stratification were 83.69, 61.81 and 41.32, respectively (sensitivity: 60.00%; specificity; 71.43% for all parameters). Pathological stage 1 (pT1) of the primary tumor was predicted by MTV60 and TLG40-50 (p = 0.0328, 0.0240, 0.0147, respectively). The optimal thresholds were 7.795, 99.55 and 77.58, respectively (sensitivity: 38.46%, 53.85% and 53.85%, respectively; specificity: 88.64%, 79.55% and 81.82%, respectively). SUVmax and SUVmean40-50-60 were the only parameters discriminating endometrioid from non-endometrioid subtype. The corresponding sensitivity was 64.86% and 62.16% for SUVmax and SUVmean 50-60 and 62.16% for SUVmean40; specificity was 70.00% for all parameters. The mean (SD) OS was 79.77% (3.34%) and the mean DFS was 77.89% (3.73%). The tumor type was the only variable significantly associated with OS (p = 0.0486). TLG50 > 77.58 cm3 was the only variable associated with a higher risk of relapse (p = 0.0472). CONCLUSION: TLG40-50-60 and MTV60 of primary EC have prognostic value in discriminating FIGO and pathological staging. These results suggest a possible role of these parameters in predicting EC aggressiveness, thus improving the preoperative characterization of endometrial cancer.

[Preliminary experience with radioimmuno-guided surgery of primary neoplasms of the lung]. / Esperienze preliminari sulla chirurgia radioimmunoguidata delle neoplasie primitive del polmone.

BACKGROUND: Radioimmunoguided surgery (RIGS) can be a valid option in the management of lung cancer as well as neoplasms in other anatomic sites. METHODS: We evaluated the usefulness of radioimmunoguided surgery (RIGS) in the staging of primitive non small cell lung cancer. Intraoperatively, this technique can define the lymph nodes involvement and thus, the radicality of the resection. In the first stage of our study, we looked for the epitope TAG 72 in 45 patients with primary non small cell lung cancer. The epitope was found by immunochemistry in only 6 cases. The only one operable patient was injected with monoclonal antibody B 72.3, that was 125I-labelled. RESULTS: At the operation, the monoclonal antibody showed no selectivity for neoplastic cells. Neoplastic tissue and healthy tissue showed a similar detection of the monoclonal antibody both intraoperatively and at the histochemical study. Because of the problems related with this method--e.g. technical difficulties, excessive wasting of time and lack of imaging--we modified our strategy. In this second stage of our study we used fragments of murine anti-CEA monoclonal antibody F023C5. The protocol was performed in 11 patients with squamous cell lung cancer. In one patient operated on for an excavated cancer(not well-defined at the immunoscintigraphy) intraoperative detection was negative while the ex vivo counts were significant: the neoplastic tissue showed a radioactivity twice higher than healthy tissue. Furthermore, the RIGS found a small intraparenchimal lymph node that was seen neither by CT nor by immunoscintigraphy. CONCLUSIONS: Our data are still preliminary, but with improvement of the technique and the use of more specific monoclonal antibodies the RIGS could become a helpful method, able to improve the radicality of surgery for lung cancer.

Unusual presentation of sarcoid-like reaction on bone marrow level associated with mediastinal lymphadenopathy on (18)F-FDG-PET/CT resembling an early recurrence of Hodgkin's Lymphoma.

(18)F-FDG-PET/CT is widely employed to evaluate lymphoma patients. False positive results are quite frequent, generally due to active phase of inflammation. We describe an unusual PET/CT presentation of a sarcoid-like reaction (SLR) in a patient monitored for Hodgkin Lymphoma characterized by an intense uptake in lymph nodes and multiple bone foci in a PET/CT study. The final diagnosis was obtained by biopsy. This study draws attention to the fact that multifocal bone marrow uptakes due to a sarcoideal reaction may be a possible cause of false positive results in (18)F-FDG-PET/CT studies in oncology patients.

Incidental detection by [11C]choline PET/CT of meningiomas in prostate cancer patients.

AIM: Anti-androgenic hormonal therapy in prostate cancer patients with concomitant meningioma may result in tumor growth and development of neurological symptoms. Positron emission tomography/computed tomography (PET/CT) with [11C]choline is used for restaging prostate cancer patients with biochemical failure. In vitro and in vivo data support altered choline metabolism in meningiomas. METHODS: During a retrospective study in prostate cancer patients with biochemical failure referred to our institution between November 2004 and January 2007, encephalic focal uptake of [11C]choline was incidentally noted in 4 patients, 2 of which had been taking luteinizing hormone-releasing hormone analogs. RESULTS: Subsequent to the incidental finding, one patient underwent surgical removal of the meningioma; strict neuroradiological follow-up was planned for the 3 other patients. CONCLUSION: We suggest that in prostate cancer patients candidate for anti-androgenic therapy the whole body [11C]choline PET/CT scan should include the whole skull to check for the possible presence of meningiomas. This could help to identify patients at risk for the development of neurological symptoms during anti-androgenic therapy and help the referring urologist in the clinical management of these patients.

Función pronóstica de los parámetros derivados de FDG PET en la estadificación preoperatoria del cáncer de endometrio / Prognostic role of FDG PET-derived parameters in preoperative staging of endometrial cancer

Objetivo: Investigar el papel pronóstico preoperatorio de la PET/TC con 18F-FDG en pacientes con carcinoma de endometrio (CE). Material y métodos: Se realizó PET/TC con 18F-FDG en 57 pacientes para el estudio preoperatorio del CE. Se evaluaron los valores de captación estandarizados máximos y medios (SUVmax, media), volumen tumoral metabólico (MTV) y glicólisis de lesión total (TLG) de tumores primarios, a diferentes umbrales de 40%, 50%, 60% (40-50-60), comparándose con las características anatomopatológicas. Se evaluó el rendimiento diagnóstico de los parámetros PET (categorizados por análisis ROC) en la discriminación de la enfermedad de bajo y mediano riesgo y el papel pronóstico en la supervivencia (supervivencia global-OS, supervivencia libre de enfermedad-SSE). Resultados: Los TLG40-50-60 categorizados fueron los únicos parámetros relacionados con FIGO estadio I versus II-III-IV (p = 0,0035 para todos). Los puntos de corte para la estratificación del riesgo fueron 83,69, 61,81 y 41,32, respectivamente (sensibilidad: 60%; especificidad, 71,43% para todos los parámetros. El estadio patológico 1 (pT1) del tumor primario se predijo con MTV60 y TLG40-50 (p = 0,0328, 0,0240 y 0,0147, respectivamente). Los umbrales óptimos fueron 7,795, 99,55 y 77,58, respectivamente (sensibilidad: 38,46%, 53,85% y 53,85%, respectivamente; especificidad: 88,64%, 79,55% y 81,82%, respectivamente). SUVmax y SUVmean40-50-60 fueron los únicos parámetros que discriminaron el subtipo endometrioide del no endometrioide. La sensibilidad fue del 64,86% y 62,16% para SUVmax y SUVmean50-60, y 62,16% para SUVmean40; la especificidad fue del 70% para todos los parámetros. La SG media (DE) fue del 79,77% (3,34%) y la SSE media fue del 77,89% (3,73%). El tipo de tumor fue la única variable significativamente asociada a la SG (p = 0,0486). TLG50 > 77,58 cm3 fue la única variable asociada a un mayor riesgo de recaída (p = 0,0472). Conclusión: TLG40-50-60 y MTV60 de EC primaria tienen valor pronóstico para discriminar FIGO y estadificación patológica. Estos resultados sugieren un posible papel de estos parámetros en la predicción de la agresividad de la CE, mejorando así la caracterización preoperatoria del cáncer de endometrio

Purpose: To investigate the preoperative prognostic role of 18F-FDG PET/CT in patients with endometrial carcinoma (EC). Methods: 18F-FDG PET/CT was performed in 57 patients for EC preoperative staging. Maximum and mean standardized uptake values (SUVmax, mean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) of primary tumors, at different thresholds of 40%, 50%, 60% (40-50-60), were evaluated and compared with anatomopathological features. The diagnostic performance of PET-parameters (categorized by ROC analysis) in discriminating low-intermediate and high-risk disease and the prognostic role on survival (overall survival -OS; disease free survival - DFS) was evaluated. Results: The categorized TLG40-50-60 were the only parameters related to FIGO stage I versus II-III-IV (p = 0.0035 for all). The cut-off values for risk stratification were 83.69, 61.81 and 41.32, respectively (sensitivity: 60.00%; specificity; 71.43% for all parameters). Pathological stage 1 (pT1) of the primary tumor was predicted by MTV60 and TLG40-50 (p = 0.0328, 0.0240, 0.0147, respectively). The optimal thresholds were 7.795, 99.55 and 77.58, respectively (sensitivity: 38.46%, 53.85% and 53.85%, respectively; specificity: 88.64%, 79.55% and 81.82%, respectively). SUVmax and SUVmean40-50-60 were the only parameters discriminating endometrioid from non-endometrioid subtype. The corresponding sensitivity was 64.86% and 62.16% for SUVmax and SUVmean 50-60 and 62.16% for SUVmean40; specificity was 70.00% for all parameters. The mean (SD) OS was 79.77% (3.34%) and the mean DFS was 77.89% (3.73%). The tumor type was the only variable significantly associated with OS (p = 0.0486). TLG50 > 77.58 cm3 was the only variable associated with a higher risk of relapse (p = 0.0472). Conclusion: TLG40-50-60 and MTV60 of primary EC have prognostic value in discriminating FIGO and pathological staging. These results suggest a possible role of these parameters in predicting EC aggressiveness, thus improving the preoperative characterization of endometrial cancer

Diagnostic and prognostic role of 99mTc-Tetrofosmin in breast cancer.

99mTc-Tetrofosmin (TF) is a lipophilic diphosphine compound routinely used for myocardial scintigraphy. Extracardiac utilization has occurred in evaluation of patients with malignant neoplasms and in parathyroid adenomas. Although its uptake mechanisms are not completely understood, they appear similar to those of 99mTc Setamibi (MIBI). The importance of flow and the metabolic status of cells with an intracellular uptake depending on mitochondria and the Na+/K+ pump have been hypothesized. It has also been demonstrated that Tetrofosmin shares with MIBI the property of being a substrate for P-glycoprotein (P-gp), a multidrug resistance transporter. In this review the possible clinical role in breast cancer is analysed. First experiences suggest that scintimammography with TF is useful in patients with indeterminate Mammography and to obtain complementary data to avoid surgery and/or biopsy. TF is a reliable tracer for diagnosis of primary cancer, of local recurrence of axillary lymph node metastases. Preliminary data stimulate a possible role in functional imaging of chemoresistance and in differential diagnosis of distant metastases with main reference to the evaluation of single hot lesions at bone scan.

Presentación inusual de reacción sarcoidea en médula ósea asociada a adenopatía mediastínica en estudio PET-TAC con 18F-FDG simulando recidiva precoz de Linfoma de Hodgkin / Unusual presentation of sarcoid-like reaction on bone marrow level associated with mediastinal lymphadenopathy on 18F-FDG-PET/CT resembling an early recurrence of Hodgkin's Lymphoma

La PET-TAC con 18F-FDG se usa habitualmente en la evaluación de pacientes con linfoma. Son frecuentes los falsos positivos, generalmente debidos a inflamación en fase activa. Describimos una presentación inusual de una reacción sarcoidea, caracterizada por una captación intensa en ganglios y en múltiples huesos, en un estudio PET en paciente en seguimiento por linfoma de Hodgkin. El diagnóstico final se obtuvo mediante biopsia. Este trabajo hace notar que captaciones múltiples óseas debidas a reacción sarcoidea pueden ser una posible causa de resultado falso positivo en estudios PET en pacientes oncológicos(AU)

18F-FDG-PET/CT is widely employed to evaluate lymphoma patients. False positive results are quite frequent, generally due to active phase of inflammation. We describe an unusual PET/CT presentation of a sarcoid-like reaction (SLR) in a patient monitored for Hodgkin Lymphoma characterized by an intense uptake in lymph nodes and multiple bone foci in a PET/CT study. The final diagnosis was obtained by biopsy. This study draws attention to the fact that multifocal bone marrow uptakes due to a sarcoideal reaction may be a possible cause of false positive results in 18F-FDG-PET/CT studies in oncology patients(AU)