Integrated 18F-fluorodeoxyglucose-positron emission tomography/dynamic contrast-enhanced computed tomography to phenotype non-small cell lung carcinoma.

We applied modern molecular and functional imaging to the pretreatment assessment of lung cancer using combined dynamic contrast-enhanced computed tomography (DCE-CT) and (18)F-fluorodeoxyglucose-positron emission tomography ((18)F-FDG-PET) to phenotype tumors. Seventy-four lung cancer patients were prospectively recruited for (18)F-FDG-PET/DCE-CT using PET/64-detector CT. After technical failures, there were 64 patients (35 males, 29 females; mean age [± SD] 67.5 ± 7.9 years). DCE-CT yielded tumor peak enhancement (PE) and standardized perfusion value (SPV). The uptake of (18)F-FDG quantified on PET as the standardized uptake value (SUV(max)) assessed tumor metabolism. The median values for SUV(max) and SPV were used to define four vascular-metabolic phenotypes. There were associations (Spearman rank correlation [rs]) between tumor size and vascular-metabolic parameters: SUV(max) versus size (rs  =  .40, p  =  .001) and SUV/PE versus size (r  =  .43, p < .001). Patients with earlier-stage (I-IIA, n  =  30) disease had mean (± SD) SUV/PE 0.36 ± 0.28 versus 0.56 ± 0.32 in later-stage (stage IIB-IV, n  =  34) disease (p  =  .007). The low metabolism with high vascularity phenotype was significantly more common among adenocarcinomas (p  =  .018), whereas the high metabolism with high vascularity phenotype was more common among squamous cell carcinomas (p  =  .024). Other non-small cell lung carcinoma tumor types demonstrated a high prevalence of the high metabolism with low vascularity phenotype (p  =  .028). We show that tumor subtypes have different vascular-metabolic associations, which can be helpful clinically in managing lung cancer patients to hone targeted therapy.

Defining the role of PET-CT in staging early breast cancer.

INTRODUCTION: Currently, there is a lack of data on the role of combined positron emission tomography-computed tomography (PET-CT) in the staging of early invasive primary breast cancer. We therefore evaluated the role of (18)F-fluorodeoxyglucose ((18)F-FDG)-PET-CT in this patient population. METHODS: We prospectively recruited 70 consecutive patients (69 women, one man; mean age, 61.9 ± 8.1 years) with early primary breast cancer for staging with (18)F-FDG-PET-CT. All PET-CT images were interpreted by two readers (independently of each other). A third reader adjudicated any discrepancies. All readers had ≥5 years of specific experience. Ethics board approval and informed consent were obtained. RESULTS: The mean clinical follow-up was 22.7 ± 12.6 months. The primary tumor was identified with PET-CT in 64 of 70 patients. Of the unidentified lesions, surgical pathology revealed two intraductal carcinomas, one invasive tubular carcinoma, and three invasive lobular carcinomas. Undiagnosed multifocal breast disease was shown in seven of 70 patients. PET-CT identified avid axillary lymph nodes in 19 of 70 patients, compared with 24 of 70 confirmed during surgery. There were four patients who were axillary node positive on PET but had no axillary disease at surgery. Five patients were reported with avid metastases. Two of those patients were treated for metastatic disease (nodal, lung, and liver in one and bone metastases in the other) following further imaging and clinical assessment. In the other three patients, lesions (lung, n = 1; pleural, n = 1; paratrachael node, n = 1) were subsequently diagnosed as benign lesions. CONCLUSION: Integrated (18)F-FDG-PET-CT may have a role in staging patients presenting with early breast cancer.

Assessment of the metabolic flow phenotype of primary colorectal cancer: correlations with microvessel density are influenced by the histological scoring method.

OBJECTIVES: To investigate how the histological scoring of microvessel density affects correlations between integrated (18)F-FDG-PET/perfusion CT parameters and CD105 microvessel density. METHODS: A total of 53 patients were enrolled from 2007 to 2010. Integrated (18)F-FDG-PET/perfusion CT was successful in 45 patients, 35 of whom underwent surgery without intervening treatment. Tumour SUV(max), SUV(mean) and regional blood flow (BF) were derived. Immunohistochemical staining for CD105 expression and analysis were performed for two hot spots, four hot spots and the Chalkley method. Correlations between metabolic flow parameters and CD105 expression were assessed using Spearman's rank correlation. RESULTS: Mean (SD) for tumour size was 38.5 (20.5) mm, for SUV(max), SUV(mean) and BF it was 19.1 (4.5), 11.6 (2.5) and 85.4 (40.3) mL/min/100 g tissue, and for CD105 microvessel density it was 71.4 (23.6), 66.8 (22.9) and 6.18 (2.07) for two hot spots, four hot spots and the Chalkley method, respectively. Positive correlation between BF and CD105 expression was modest but higher for Chalkley than for four hot spots analysis (r = 0.38, P = 0.03; r = 0.33, P = 0.05, respectively). There were no significant correlations between metabolic parameters (SUV(max) or SUV(mean)) and CD105 expression (r = 0.08-0.22, P = 0.21-0.63). CONCLUSIONS: The histological analysis method affects correlations between tumour CD105 expression and BF but not SUV(max) or SUV(mean). KEY POINTS: • FDG-PET/perfusion CT offers new surrogate biomarkers of angiogenesis. • Microvessel density scoring influences histopathological correlations with CT blood flow. • Highest correlations were found with the Chalkley analysis method. • Correlations between SUV and CD105 are not affected by the scoring method.

A Phase II, Open-label study to assess safety and management change using 68Ga-THP PSMA PET/CT in patients with high risk primary prostate cancer or biochemical recurrence after radical treatment: The PRONOUNCED study.

Objectives: To assess the safety and clinical impact of a novel, kit-based formulation of 68Ga-THP PSMA positron emission tomography/computed tomography (PET/CT) when used to guide the management of patients with prostate cancer (PCa). Methods: Patients were prospectively recruited in to one of: Group A: high-risk untreated prostate cancer; Gleason score >4+3, or PSA >20 ng/mL or clinical stage >T2c. Group B: biochemical recurrence (BCR) and eligible for salvage treatment after radical prostatectomy with two consecutive rises in prostate specific antigen (PSA) with a three month interval in between reads and final PSA >0.1 ng/mL or a PSA level >0.5 ng/mL. Group C: BCR with radical curative radiotherapy or brachytherapy at least three months prior to enrolment, and an increase in PSA level >2.0 ng/mL above the nadir level after radiotherapy or brachytherapy. Patients underwent evaluation with PET/CT 60 minutes following intravenous administration of 160±30 MBq of 68Ga-THP PSMA. Safety was assessed by means including vital signs, cardiovascular profile, serum haematology, biochemistry, urinalysis, PSA, and Adverse Events (AEs). A change in management was reported when the predefined clinical management of the patient altered as a result of 68Ga-THP PSMA PET/CT findings. Results: Forty-nine patients were evaluated with PET/CT; 20 in Group A, 21 in Group B and 8 in Group C. No patients experienced serious AEs discontinued the study due to AEs, or died during the study. Two patients had Treatment Emergent AEs attributed to 68Ga-THP-PSMA (pruritus in one patient and intravenous catheter site rash in another). Management change secondary to PET/CT occurred in 42.9% of all patients; 30% in Group A, 42.9% in Group B and 75% in Group C. Conclusion: 68Ga-THP PSMA was safe to use with no serious AE and no AE resulting in withdrawal from the study. 68Ga-THP PSMA PET/CT changed the management of patients in 42.9% of the study population, comparable to studies using other PSMA tracers. These data form the basis of a planned Phase III study of 68Ga-THP PSMA in patients with prostate cancer.

Multifunctional imaging signature for V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in colorectal cancer.

UNLABELLED: This study explores the potential for multifunctional imaging to provide a signature for V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutations in colorectal cancer. METHODS: This prospective study approved by the institutional review board comprised 33 patients undergoing PET/CT before surgery for proven primary colorectal cancer. Tumor tissue was examined histologically for presence of the KRAS mutations and for expression of hypoxia-inducible factor-1 (HIF-1) and minichromosome maintenance protein 2 (mcm2). The following imaging parameters were derived for each tumor: (18)F-FDG uptake ((18)F-FDG maximum standardized uptake value [SUVmax]), CT texture (expressed as mean of positive pixels [MPP]), and blood flow measured by dynamic contrast-enhanced CT. A recursive decision tree was developed in which the imaging investigations were applied sequentially to identify tumors with KRAS mutations. Monte Carlo analysis provided mean values and 95% confidence intervals for sensitivity, specificity, and accuracy. RESULTS: The final decision tree comprised 4 decision nodes and 5 terminal nodes, 2 of which identified KRAS mutants. The true-positive rate, false-positive rate, and accuracy (95% confidence intervals) of the decision tree were 82.4% (63.9%-93.9%), 0% (0%-10.4%), and 90.1% (79.2%-96.0%), respectively. KRAS mutants with high (18)F-FDG SUVmax and low MPP showed greater frequency of HIF-1 expression (P = 0.032). KRAS mutants with low (18)F-FDG SUV(max), high MPP, and high blood flow expressed mcm2 (P = 0.036). CONCLUSION: Multifunctional imaging with PET/CT and recursive decision-tree analysis to combine measurements of tumor (18)F-FDG uptake, CT texture, and perfusion has the potential to identify imaging signatures for colorectal cancers with KRAS mutations exhibiting hypoxic or proliferative phenotypes.

Tumor heterogeneity and permeability as measured on the CT component of PET/CT predict survival in patients with non-small cell lung cancer.

PURPOSE: We prospectively examined the role of tumor textural heterogeneity on positron emission tomography/computed tomography (PET/CT) in predicting survival compared with other clinical and imaging parameters in patients with non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: The feasibility study consisted of 56 assessed consecutive patients with NSCLC (32 males, 24 females; mean age 67 ± 9.7 years) who underwent combined fluorodeoxyglucose (FDG) PET/CT. The validation study population consisted of 66 prospectively recruited consecutive consenting patients with NSCLC (37 males, 29 females; mean age, 67.5 ± 7.8 years) who successfully underwent combined FDG PET/CT-dynamic contrast-enhanced (DCE) CT. Images were used to derive tumoral PET/CT textural heterogeneity, DCE CT permeability, and FDG uptake (SUVmax). The mean follow-up periods were 22.6 ± 13.3 months and 28.5± 13.2 months for the feasibility and validation studies, respectively. Optimum threshold was determined for clinical stage and each of the above biomarkers (where available) from the feasibility study population. Kaplan-Meier analysis was used to assess the ability of the biomarkers to predict survival in the validation study. Cox regression determined survival factor independence. RESULTS: Univariate analysis revealed that tumor CT-derived heterogeneity (P < 0.001), PET-derived heterogeneity (P = 0.003), CT-derived permeability (P = 0.002), and stage (P < 0.001) were all significant survival predictors. The thresholds used in this study were derived from a previously conducted feasibility study. Tumor SUVmax did not predict survival. Using multivariable analysis, tumor CT textural heterogeneity (P = 0.021), stage (P = 0.001), and permeability (P < 0.001) were independent survival predictors. These predictors were independent of patient treatment. CONCLUSIONS: Tumor stage and CT-derived textural heterogeneity were the best predictors of survival in NSCLC. The use of CT-derived textural heterogeneity should assist the management of many patients with NSCLC.