Maria Picchio

Early lung-cancer detection with spiral CT and positron emission tomography in heavy smokers: 2-year results

BACKGROUND Low-dose spiral CT of the chest effectively detects early-stage lung cancer in high-risk individuals. The high rate of benign nodules and issues of making a differential diagnosis are critical factors that currently hamper introduction of large-scale screening programmes. We investigated the efficacy of repeated yearly spiral CT and selective use of positron emission tomography (PET) in a large cohort of high-risk volunteers. METHODS We enrolled 1035 individuals aged 50 years or older who had smoked for 20 pack-years or more. All patients underwent annual low-dose CT, with or without PET, for 5 years. Lesions up to 5 mm were deemed non-suspicious and low-dose CT was repeated after 12 months (year 2). FINDINGS By year 2, 22 cases of lung cancer had been diagnosed (11 at baseline, 11 at year 2). 440 lung lesions were identified in 298 (29%) participants, and 95 were recalled for high-resolution contrast CT. PET scans were positive in 18 of 20 of the identified cancer cases. Six patients underwent surgical biopsy for benign disease because of false-positive results (6% of recalls, 22% of invasive procedures). Complete resection was achieved in 21 (95%) lung cancers, 17 (77%) were pathological stage I (100% at year 2), and the mean tumour size was 18 mm. There were no interval lung cancers in the 2.5 years of follow-up (average time on study from randomisation to last contact), although 19 individuals were diagnosed with another form of cancer (two deaths and 17 non-fatal admissions). INTERPRETATION Combined use of low-dose spiral CT and selective PET effectively detects early lung cancer. Lesions up to 5 mm can be checked again at 12 months without major risks of progression.

11C-Choline Positron Emission Tomography/Computerized Tomography for Preoperative Lymph-Node Staging in Intermediate-Risk and High-Risk Prostate Cancer: Comparison with Clinical Staging Nomograms

BACKGROUND Conventional imaging (CI) techniques are inadequate for lymph node (LN) staging in prostate cancer (PCa). OBJECTIVES To assess the accuracy of (11)C-Choline positron emission tomography/computerized tomography (PET/CT) for LN staging in intermediate-risk and high-risk PCa and to compare it with two currently used nomograms. DESIGN, SETTING, AND PARTICIPANTS From January 2007 to September 2007, 57 PCa patients at intermediate risk (n=27) or high risk (n=30) were enrolled at two academic centres. All patients underwent preoperative PET/CT and radical prostatectomy with extended pelvic LN dissection (PLND). Risk of LN metastasis (LNM) was assessed using available nomograms. MEASUREMENTS Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and number of correctly recognized cases for LNM detection at PET/CT were assessed. The accuracy of PET/CT for LNM detection was compared with the accuracy of nomograms for LNM prediction by using receiver operating characteristic (ROC) analysis. RESULTS AND LIMITATIONS Fifteen patients (26%) had LNMs, and a total of 41 LNMs were identified. On a patient analysis, sensitivity, specificity, PPV, NPV, and number of correctly recognized cases at PET/CT were 60.0%, 97.6%, 90.0%, 87.2%, and 87.7% while, on node analysis, these numbers were 41.4%, 99.8%, 94.4%, 97.2%, and 97.1%. The mean diameter (in mm) of the metastatic deposit of true-positive LNs was significantly higher than that of false-negative LNs (9.2 vs 4.2; p=0.001). PET/CT showed higher specificity and accuracy than the nomograms; however, in pairwise comparison, the areas under the curve (AUCs) were not statistically different (all p values >0.05). CONCLUSIONS In patients with intermediate-risk and high-risk PCa, (11)C-Choline PET/CT has quite a low sensitivity for LNM detection but performed better than clinical nomograms, with equal sensitivity and better specificity.

Physical performance of the new hybrid PET∕CT Discovery-690.

PURPOSE The aim of this work was the assessment of the physical performance of the new hybrid PET∕CT system: Discovery-690. METHODS The Discovery-690 combines a lutetium-yttrium-orthosilicate (LYSO) block detector designed PET tomograph with a 64-slice CT scanner. The system is further characterized by a dedicated powerful computing platform implementing fully 3D-PET iterative reconstruction algorithms. These algorithms can account for time of flight (TOF) information and∕or a 3D model of the PET point spread function (PSF). PET physical performance was measured following NEMA NU-2-2007 procedures. Furthermore, specific tests were used: (i) to measure the energy and timing resolution of the PET system and (ii) to evaluate image quality, by using phantoms representing different clinical conditions (e.g., brain and whole body). Data processing and reconstructions were performed as required by standard procedures. Further reconstructions were carried out to evaluate the performance of the new reconstruction algorithms. In particular, four algorithms were considered for the reconstruction of the PET data: (i) HD = standard configuration, without TOF and PSF, (ii) TOF = HD + TOF, (iii) PSF = HD + PSF, and (iv) TOFPSF = HD + TOF + PSF. RESULTS The transverse (axial) spatial resolution values were 4.70 (4.74) mm and 5.06 (5.55) mm at 1 cm and 10 cm off axis, respectively. Sensitivity (average between 0 and 10 cm) was 7.5 cps∕kBq. The noise equivalent count rate (NECR) peak was 139.1 kcps at 29.0 kBq∕ml. The scatter fraction at the NECR peak was 37%. The correction accuracy for the dead time losses and random event counts had a maximum absolute error below the NECR peak of 2.09%. The average energy and timing resolution were 12.4% and 544.3 ps, respectively. PET image quality was evaluated with the NEMA IEC Body phantom by using four reconstruction algorithms (HD, TOF, PSF, and TOFPSF), as previously described. The hot contrast (after 3 iterations and for a lesion∕background activity ratio of 4:1) for the spheres of 10, 13, 17, and 22 mm was (HD) 29.8, 45.4, 55.4, and 68.1%; (TOF) 39.9, 53.5, 62.7, and 72.2%; (PSF) 28.3, 47.3, 60.4, and 71.8%; (TOFPSF) 43.8, 62.9, 70.6, and 76.4%. The cold contrast for the spheres of 28 and 37 mm was (HD) 62.4 and 65.2%; (TOF) 77.1 and 81.4%; (PSF) 62.0 and 65.2%; (TOFPSF) 77.3 and 81.6%. Similar hot and cold contrast trends were found during the analyses of other phantoms representing different clinical conditions (brain and whole body). Nevertheless, the authors observed a predominant role of either TOF or PSF, depending on the specific characteristics and dimensions of the phantoms. CONCLUSIONS Discovery-690 shows very good PET physical performance for all the standard NEMA NU-2-2007 measurements. Furthermore, the new reconstruction algorithms available for PET data (TOF and PSF) allow further improvements of the D-690 image quality performance both qualitatively and quantitatively.

Positron Emission Tomography for Radiation Treatment Planning

Purpose:To evaluate the impact of positron emission tomography (PET) on target volume delineation for radiation treatment planning.Material and Methods:The data of the literature concerning the use of PET in target volume delineation are summarized. The following points are discussed for each tumor entity: biological background for the PET investigation, sensitivity and specificity of PET (with different tracers) in comparison to computed tomography (CT) and magnetic resonance imaging (MRI) and impact of PET on target volume definition. New PET tracers, which could visualize biological pathways, such as hypoxia, proliferation, angiogenesis, apoptosis and gene expression patterns, will also be discussed.Results:The results of clinical studies on the integration of PET in target volume definition for lung, head-and-neck, genitourinary and brain tumors were analyzed. Fluorodeoxyglucose-(FDG-)PET has a significant impact on GTV (gross tumor volume) and PTV (planning target volume) delineation in lung cancer and can detect lymph node involvement and differentiate malignant tissue from atelectasis. In head-and-neck cancer, the value of FDG-PET for radiation treatment planning is still under investigation. For example, FDG-PET could be superior to CT and MRI in the detection of lymph node metastases and unknown primary cancer and in the differentiation of viable tumor tissue after treatment. Therefore, it might play an important role in GTV definition and sparing of normal tissue. Choline PET and acetate PET are promising tracers in the diagnosis of prostate cancer, but their validity in local tumor demarcation, lymph node diagnosis and detection of recurrence has to be defined in future clinical trials. FDG-PET seems to be particularly valuable in lymph node status definition in cervical cancer. In high-grade gliomas and meningiomas, methionine PET helps to define the GTV and differentiate tumor from normal tissue. For other entities like gastrointestinal cancer, lymphomas, sarcomas, etc., the data of the literature are yet insufficient. The imaging of hypoxia, cell proliferation, angiogenesis, apoptosis and gene expression leads to the identification of different areas of a biologically heterogeneous tumor mass that can individually be targeted using intensity modulated radiotherapy (IMRT). In addition, a biological dose distribution can be generated, the socalled dose painting. However, systematic experimental and clinical trials are necessary to validate this hypothesis.Conclusion:Regarding treatment planning in radiotherapy, PET offers advantages in terms of tumor delineation and the description of biological processes. To define the real impact of this investigation in radiation treatment planning, subsequent experimental, clinical and cost-benefit analyses are required.Ziel:Untersuchung der Wertigkeit der Positronenemissionstomographie (PET) für die Strahlentherapieplanung.Material und Methodik:Die Arbeit fasst die Daten aus der Literatur zur Integration der PET in die Zielvolumendefinition für die Entitäten Lungen-, Kopf-Hals , Becken- und Hirntumoren zusammen. Für jede Tumorentität werden folgende Punkte diskutiert: der biologische Hintergrund der PET-Untersuchung, die Sensitivität und Spezifität (mit verschiedenen Tracern) im Vergleich zur Computertomographie (CT) und Magnetresonanztomographie (MRT) und der Einfluss auf die Zielvolumendefinition. Neue Tracer, die für die Strahlentherapie wichtige biologische Vorgänge abbilden, werden diskutiert: Hypoxie, Proliferation, Angiogenese, Apoptose, Genexpression.Ergebnisse:Die Fluorodesoxyglucose-(FDG-)PET hat einen signifikanten Einfluss auf die Zielvolumendefinition bei Lungentumoren, insbesondere in der Diagnose pathologischer Lymphknoten und in der Abgrenzung des Tumors von einer Atelektase. Bei Kopf-Hals-Tumoren ist der Stellenwert der PET noch offen: Die FDG-PET könnte der CT und MRT in der Diagnose von Lymphknotenmetastasen, der Suche des Primärtumors bei CUP und der differentialdiagnostischen Abgrenzung des Primär- oder Rezidivtumors von einer Nekrose nach Therapie überlegen sein. Hierdurch könnten die Definition des Zielvolumens und die Schonung des Normalgewebes maßgeblich beeinflusst werden. In der Diagnostik des Prostatakarzinoms finden sich erste, vielversprechende Daten zur Cholin- bzw. Acetat-PET. Die Präzision bei der Bestimmung der Ausdehnung von Primärtumor und Lymphknotenmetastasen sowie der Diagnostik eines Tumorrezidivs muss noch in weiteren klinischen Studien bestimmt werden. Die FDG-PET ist vor allem in der Detektion von Lymphknotenmetastasen des Zervixkarzinoms nützlich. Bei „High-grade“-Gliomen und Meningeomen hat die Methionin-PET eine große Bedeutung für die Definition des Zielvolumens durch die präzise Unterscheidung von Tumor- und Normalgewebe. Für andere Tumorentitäten (gastrointestinale Tumoren, Lymphome, Sarkome etc.) sind die Daten aus der Literatur noch unzureichend. Die Darstellung von Tumorhypoxie, Proliferation, Angiogenese, Apoptose oder Genexpression kann zur Identifikation strahlenbiologisch unterschiedlicher Areale eines inhomogenen Tumors führen. Die biologische Bildgebung könnte so der intensitätsmodulierten Radiotherapie (IMRT) die Informationen für eine gezielt inhomogene Dosisverteilung liefern, um im Rahmen des sog. Dose-Painting Gebiete vermeintlich höherer Strahlenresistenz gezielt mit höheren Dosen zu behandeln. Diese Hypothese wurde allerdings bislang nicht in klinischen Studien untersucht.Schlussfolgerung:Die Integration der PET in die Strahlentherapieplanung beeinflusst die Zielvolumendefinition bei der Strahlentherapie vieler solider Tumoren. In Zukunft könnte sie vor allem durch eine präzise Definition der Tumorgrenzen und die Darstellung wichtiger biologischer Vorgänge weitere Bedeutung gewinnen. Experimentelle und klinische Untersuchungen sowie Kosten-Nutzen-Analysen sind allerdings notwendig, um den Stellenwert dieser Untersuchung für die Strahlentherapieplanung genauer zu definieren.

Pelvic/Retroperitoneal Salvage Lymph Node Dissection for Patients Treated With Radical Prostatectomy With Biochemical Recurrence and Nodal Recurrence Detected by [11C]Choline Positron Emission Tomography/Computed Tomography

BACKGROUND The management of patients with clinical recurrence of prostate cancer after radical prostatectomy (RP) remains challenging. OBJECTIVE To determine whether the removal of positive lymph nodes at [11C]choline positron emission tomography/computed tomography (PET/CT) scan may have an impact on the prognosis of patients with biochemical recurrence (BCR) and nodal recurrence after RP. DESIGN, SETTING, AND PARTICIPANTS Prospective analysis of 72 patients affected by BCR after RP associated with a nodal pathologic [11C]choline PET/CT scan. INTERVENTION Patients underwent salvage lymph node dissection (LND). MEASUREMENTS Biochemical response (BR) to treatment was defined as prostate-specific antigen (PSA) <0.2 ng/ml at 40 d after salvage LND. Kaplan-Meier and Cox regression analyses addressed time to and predictors of clinical recurrence (CR) after salvage LND, respectively. RESULTS AND LIMITATIONS Overall, 56.9% of patients achieved BR. Mean and median follow-up after LND were 39.4 and 39.8 mo, respectively. The 5-yr BCR-free survival rate was 19%. Preoperative PSA <4 ng/ml (hazard ratio [HR]: 0.12; p = 0.005), time to BCR <24 mo (HR: 7.52; p = 0.005), and negative lymph nodes at previous RP (HR: 0.19; p=0.04) represented independent predictors of BR. Overall, 5-yr CR-free and cancer-specific survival were 34% and 75%, respectively. At multivariable analyses, only PSA >4 ng/ml (HR: 2.13; p=0.03) and the presence of retroperitoneal uptake at PET/CT scan (HR=2.92; p=0.004) represented independent preoperative predictors of CR. Similarly, the presence of pathologic nodes in the retroperitoneum (HR: 2.78; p=0.02), higher number of positive lymph nodes (HR: 1.04; p=0.006), and complete BR to salvage LND (HR: 0.31; p=0.002) represented postoperative independent predictors of CR. Main limitations consisted of the lack of a control group and the heterogeneity of patients included in the analyses. CONCLUSIONS Salvage LND is feasible in patients with BCR after RP and nodal pathologic uptake at [11C]choline PET/CT scan. Biochemical response after surgery can be achieved in a consistent proportion of patients. Although most patients invariably progressed to BCR after surgery at longer follow-up, 35% of patients showed the absence of CR at 5 yr.

Long-term Outcomes of Salvage Lymph Node Dissection for Clinically Recurrent Prostate Cancer: Results of a Single-institution Series with a Minimum Follow-up of 5 Years

BACKGROUND Prostate cancer (PCa) patients with lymph node recurrence after radical prostatectomy (RP) are usually managed with androgen-deprivation therapy. Despite the absence of prospective randomized studies, salvage lymph node dissection (LND) has been proposed as an alternative treatment option. OBJECTIVE To examine long-term outcomes of salvage LND in patients with nodal recurrent PCa documented by 11C-choline positron emission tomography/computed tomography (PET/CT) scan. DESIGN, SETTING, AND PARTICIPANTS Overall, 59 patients affected by biochemical recurrence (BCR) with 11C-choline PET/CT scan with pathologic activity treated between 2002 and 2008 were included. INTERVENTION Pelvic and/or retroperitoneal salvage LND. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES Biochemical response (BR) was defined as prostate-specific antigen (PSA) <0.2 ng/ml at 40 d after surgery. BCR for those who achieved BR was defined as a PSA >0.2 ng/ml. Clinical recurrence (CR) was defined as a positive PET/CT scan after salvage LND in the presence of a rising PSA. Kaplan-Meier curves assessed time to BCR, CR, and cancer-specific mortality (CSM). Cox regression analyses were fitted to assess predictors of CR. RESULTS AND LIMITATIONS Median follow-up after salvage LND was 81.1 mo. Overall, 35 patients (59.3%) achieved BR. The 8-yr BCR-free survival rate in patients with complete BR was 23%. Overall, the 8-yr CR- and CSM-free survival rates were 38% and 81%, respectively. In multivariable analyses evaluating preoperative variables, PSA at salvage LND represented the only predictor of CR (p=0.03). When postoperative variables were considered, BR and the presence of retroperitoneal lymph node metastases were significantly associated with the risk of CR (all p ≤ 0.04). Our study is limited by the lack of a control group. CONCLUSIONS Salvage LND may represent a therapeutic option for patients with BCR after RP and nodal pathologic uptake at 11C-choline PET/CT scan. Although most patients progressed to BCR after salvage LND, roughly 40% of them experienced CR-free survival. PATIENT SUMMARY Salvage lymph node dissection may represent a therapeutic option for selected patients with nodal recurrence after radical prostatectomy. Roughly 40% of men did not show any further clinical recurrence at long-term follow-up after surgery.

Value of integrated PET/CT for lesion localisation in cancer patients: a comparative study

The aim of this study was to retrospectively compare the value of integrated PET/CT and separate PET plus morphological imaging studies for lesion localisation in cancer patients. Two different series of consecutive patients who had previously been treated for neoplastic disease were considered. One series consisted of 105 patients who had undergone [18F]fluorodeoxyglucose (FDG) PET/CT (n=70) or [11C]choline PET/CT (n=35) studies (PET/CT group). The other series comprised 105 patients who had undergone FDG PET scan (n=70) or [11C]choline PET scan (n=35) alone; in this series, PET findings were correlated with the results of morphological imaging (MI) studies, i.e. CT (n=92) or MR imaging (n=13) (PET+MI group). Regions of abnormal tracer uptake at PET scanning were classified as ambiguous or unambiguous depending on their precise anatomical localisation. A total of 207 and 196 lesions were found in the PET/CT and PET+MI groups, respectively. The difference in terms of number of lesions per patient detected with the two imaging protocols was not statistically significant (P=0.718). When analysis of lesion localisation was performed, there were 7/207 (3.4%) and 30/196 (15.3%) ambiguous lesions in the PET/CT and PET+MI groups, respectively. The number of ambiguous lesions was significantly higher in the PET+MI group than in the PET/CT group (χ2=15.768, P<0.0001). Comparison of the effect of use of the different tracers on reporting of PET/CT versus PET+MI revealed that the improvement in the final report in [11C]choline PET/CT studies was similar to that observed in [18F]FDG studies. In cancer patients, PET/CT shows higher diagnostic accuracy for lesion localisation than PET plus morphological imaging studies performed independently. This result does not seem to be affected by the type of tracer used.

When to Perform Bone Scan in Patients with Newly Diagnosed Prostate Cancer: External Validation of the Currently Available Guidelines and Proposal of a Novel Risk Stratification Tool

BACKGROUND Several guidelines have indicated that in patients with well-differentiated or moderately well-differentiated prostate cancer (PCa), a staging bone scan may be omitted. However, the guidelines recommendations have not yet been externally validated. OBJECTIVE The aim of the study was to externally validate the available guidelines regarding the need for a staging bone scan in patients with newly diagnosed PCa. Moreover, we developed a novel risk stratification tool aimed at improving the accuracy of these guidelines. DESIGN, SETTING, AND PARTICIPANTS The study included 853 consecutive patients diagnosed with PCa between January 2003 and June 2008 at a single centre. All patients underwent bone scan using technetium Tc 99m methylene diphosphonate at diagnosis. MEASUREMENTS The area under the curve (AUC) of the criteria suggested by the guidelines (European Association of Urology, American Urological Association, National Comprehensive Cancer Network, and American Joint Committee on Cancer) to perform a baseline bone scan was assessed and compared with the accuracy of a classification and regression tree (CART) including prostate-specific antigen (PSA), clinical stage, and biopsy Gleason sum as covariates. RESULTS AND LIMITATIONS The AUC of the guidelines ranged between 79.7% and 82.6%. However, the novel CART model, which stratified patients into low risk (biopsy Gleason ≤7, cT1-T3, and PSA <10 ng/ml), intermediate risk (biopsy Gleason ≤7, cT2/T3, and PSA >10 ng/ml), and high risk (biopsy Gleason >7) was significantly more accurate (AUC: 88.0%) than all the guidelines (all p≤0.002). The limitation of this study resides in its retrospective design. Moreover, the proposed risk stratification tool can be considered only for patients who are candidates for radical prostatectomy until validated in other clinical settings. CONCLUSIONS This is the first study aimed at externally validating the available guidelines addressing the need for staging baseline bone scans in PCa patients. All guidelines showed high accuracy. However, their accuracy was significantly lower compared with the accuracy of the novel risk stratification tool. According to this tool, staging bone scans might be considered only for patients with a biopsy Gleason score >7 or with a PSA >10 ng/ml and palpable disease (cT2/T3) prior to treatment. However, before recommending its use in clinical practice, our model needs to be externally validated.

Role of the integrated FDG PET/CT in the surgical management of patients with high risk clinical early stage endometrial cancer: Detection of pelvic nodal metastases

BACKGROUND High risk clinical stage I endometrial cancer (grade 2 and deep myometrial invasion, grade 3 and serous and clear-cell carcinoma) had 10-35% of nodal involvement. Surgical staging is considered reasonable in this setting of women, although unnecessary in 70-90%. The purpose of this study was to determine prospectively the diagnostic accuracy of 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography 18F-FDG PET/CT in the detection of nodal metastases in patients with high risk endometrial cancer. METHODS Eleven women with grade 2 and deep myometrial invasion and 26 with grade 3 endometrial cancer underwent 18F-FDG PET/CT, followed by total hysterectomy, bilateral salpingo-oophorectomy and systematic pelvic lymphadenectomy. Histopathological findings served as the reference standard. Diagnostic performance of 18F-FDG PET/CT in nodal disease detection was reported in terms of accuracy value both in a patient-based and a lesion site-based analysis. RESULTS Pelvic nodes metastases were found at histopathological analysis in 9 of the 37 patients (24.3%). Patient-based sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 18F-FDG PET/CT for detection of nodal disease were 77.8%, 100.0%, 100.0%, 93.1% and 94.4%, respectively. Nodal lesion site-based sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 18F-FDG PET/CT were 66.7%, 99.4%, 90.9%, 97.2% and 96.8%, respectively. CONCLUSION This study shows that 18F-FDG PET/CT is an accurate method for the presurgical evaluation of pelvic nodes metastases. The high negative predictive value may be useful in selecting patients who only may benefit from lymphadenectomy, minimizing operative and surgical complications.

PET/CT and breast cancer.

During the past decade, the application of positron emission tomography with [18F]fluoro-2-deoxy-d-glucose (FDG-PET) has remarkably improved the management of cancer patients. Nevertheless, the clinical interpretation of FDG-PET scan can be difficult for two main reasons: (1) anatomical localisation of FDG uptake is not easy, (2) normal physiological accumulation of FDG can be misinterpreted as a pathologic area. It has been demonstrated that the visual correlation of PET with morphological procedures, such as computed tomography or magnetic resonance imaging, can improve the accuracy of PET alone. However, the time interval between the two scans, the time employed by the operator and difficulties in co-registering imaging of the abdomen and pelvis make the co-registration of separately obtained images clinically difficult. A novel combined PET/CT system has been built that improves the capacity to correctly localise and interpret FDG uptake. To date only a few studies have been conducted on the potential role of PET/CT in the management of breast cancer patients, but the better performance of this technique compared with PET alone should also be relevant for breast cancer application. In this review, we evaluate the possible impact on breast cancer diagnosis of PET/CT compared with PET alone, with respect to disease re-staging, treatment monitoring, preoperative staging and primary diagnosis. In addition, the possible role of PET/CT for radiotherapy planning is evaluated.