PET/CT reading for relapse in non-small cell lung cancer after chemoradiotherapy in the PET-Plan trial cohort.

BACKGROUND: Current studies indicate that fluorine-18-fluorodeoxyglucose positron emission tomography/ computed tomography ([18F]FDG PET/CT) is the most accurate imaging modality for the detection of relapsed locally advanced non-small cell lung cancer (NSCLC) after curatively intended chemoradiotherapy. To this day, there is no objective and reproducible definition for the diagnosis of disease recurrence in PET/CT, the reading of which is relevantly influenced by post radiation inflammatory processes. The aim of this study was to evaluate and compare visual and threshold-based semi-automated evaluation criteria for the assessment of suspected tumor recurrence in a well-defined study population investigated during the randomized clinical PET-Plan trial. METHODS: This retrospective analysis comprises 114 PET/CT data sets of 82 patients from the PET-Plan multi-center study cohort who underwent [18F]FDG PET/CT imaging at different timepoints for relapse, as suspected by CT. Scans were first analyzed visually by four blinded readers using a binary scoring system for each possible localization and the associated reader certainty of the evaluation. Visual evaluations were conducted repeatedly without and with additional knowledge of the initial staging PET and radiotherapy delineation volumes. In a second step, uptake was measured quantitatively using maximum standardized uptake value (SUVmax), peak standardized uptake value corrected for lean body mass (SULpeak), and a liver threshold-based quantitative assessment model. Resulting sensitivity and specificity for relapse detection were compared to the findings in the visual assessment. The gold standard of recurrence was independently defined by prospective study routine including external reviewers using CT, PET, biopsies and clinical course of the disease. RESULTS: Overall interobserver agreement (IOA) of the visual assessment was moderate with a high difference between secure (ĸ = 0.66) and insecure (ĸ = 0.24) evaluations. Additional knowledge of the initial staging PET and radiotherapy delineation volumes improved the sensitivity (0.85 vs 0.92) but did not show significant impact on the specificity (0.86 vs 0.89). PET parameters SUVmax and SULpeak showed lower accuracy compared to the visual assessment, whereas threshold-based reading showed similar sensitivity (0.86) and higher specificity (0.97). CONCLUSION: Visual assessment especially if associated with high reader certainty shows very high interobserver agreement and high accuracy that can be further increased by baseline PET/CT information. The implementation of a patient individual liver threshold value definition, similar to the threshold definition in PERCIST, offers a more standardized method matching the accuracy of experienced readers albeit not providing further improvement of accuracy.

Neoadjuvant chemoradiation with paclitaxel/carboplatin for selected Stage III non-small-cell lung cancer: long-term results of a trimodality Phase II protocol.

PURPOSE: To evaluate, in a Phase II trial conducted August 1998 through January 2001, the efficacy of neoadjuvant chemotherapy followed by chemoradiotherapy and definitive surgery in patients with locally advanced non-small-cell lung cancer (LA-NSCLC), Stages IIIA bulky and selected Stage IIIB. PATIENTS AND METHODS: Staging of LA-NSCLC included computed tomography of cranium, thorax, and abdomen, whole-body positron emission tomography, and video mediastinoscopy. Induction chemotherapy with weekly paclitaxel and carboplatin was followed by hyperfractionated accelerated thoracic radiotherapy (45 Gy) with simultaneous weekly paclitaxel and carboplatin. Four to six weeks after completion of induction therapy, restaging and resection of primary tumor and lymph nodes was intended. RESULTS: A total of 59 consecutive patients were enrolled, 25% with Stage IIIA bulky disease, 65% with Stage IIIB, and 10% with Stage IV (excluded from further analysis). Forty-one patients completed induction therapy; in 52.4% a functional (positron emission tomography) downstaging was proven. Thirty-two patients (59.3%) underwent complete tumor resection, and 5 patients had an exploratory thoracotomy only. Histopathologic downstaging was proven in 59.4% and complete response in 21.9%. Hospital mortality was 5.4%. Median duration of follow-up for living patients was 62.1 months. Overall median survival was 22.6 months, 58.2 months for completely resected patients. During induction chemotherapy, Grade 3/4 granulocytopenia occurred in 8% of patients; the most common Grade 3/4 toxicity of chemoradiation was esophagitis, in 26.4% of patients. CONCLUSIONS: Induction paclitaxel/carboplatin with hyperfractionated accelerated chemoradiotherapy followed by complete tumor resection demonstrates high efficacy in LA-NSCLC and offers a promising chance of long-term survival.

[68Ga]-DOTATOC-PET/CT for meningioma IMRT treatment planning.

PURPOSE: The observation that human meningioma cells strongly express somatostatin receptor (SSTR 2) was the rationale to analyze retrospectively in how far DOTATOC PET/CT is helpful to improve target volume delineation for intensity modulated radiotherapy (IMRT). PATIENTS AND METHODS: In 26 consecutive patients with preferentially skull base meningioma, diagnostic magnetic resonance imaging (MRI) and planning-computed tomography (CT) was complemented with data from [(68)Ga]-DOTA-D Phe(1)-Tyr(3)-Octreotide (DOTATOC)-PET/CT. Image fusion of PET/CT, diagnostic computed tomography, MRI and radiotherapy planning CT as well as target volume delineation was performed with OTP-Masterplan((R)). Initial gross tumor volume (GTV) definition was based on MRI data only and was secondarily complemented with DOTATOC-PET information. Irradiation was performed as EUD based IMRT, using the Hyperion Software package. RESULTS: The integration of the DOTATOC data led to additional information concerning tumor extension in 17 of 26 patients (65%). There were major changes of the clinical target volume (CTV) which modify the PTV in 14 patients, minor changes were realized in 3 patients. Overall the GTV-MRI/CT was larger than the GTV-PET in 10 patients (38%), smaller in 13 patients (50%) and almost the same in 3 patients (12%). Most of the adaptations were performed in close vicinity to bony skull base structures or after complex surgery. Median GTV based on MRI was 18.1 cc, based on PET 25.3 cc and subsequently the CTV was 37.4 cc. Radiation planning and treatment of the DOTATOC-adapted volumes was feasible. CONCLUSION: DOTATOC-PET/CT information may strongly complement patho-anatomical data from MRI and CT in cases with complex meningioma and is thus helpful for improved target volume delineation especially for skull base manifestations and recurrent disease after surgery.

Tumor detection by diffusion-weighted MRI and ADC-mapping--initial clinical experiences in comparison to PET-CT.

OBJECTIVE: To evaluate the clinical potential of diffusion-weighted-imaging (DWI) with apparent diffusion coefficient (ADC)-mapping for tumor detection. MATERIALS AND METHODS: A single-shot echo-planar-imaging DWI sequence with fat suppression and ability for navigator-based respiratory triggering was implemented. Nineteen patients (11 melanoma, 4 prostate cancer, 1 non-Hodgkin lymphoma, and 3 lung cancer) were examined by positron emission tomography (PET) with an integrated computed tomography scanner (PET-CT) and DWI. Images at b = 0, 400, and 1000 s/mm2 were acquired and ADC maps were generated. PET examinations were used as a reference for tumor detection. Four hundred twenty-four regions of interest were used for DWI and 73 for PET data evaluation. RESULTS: DWI and ADC maps were of diagnostic quality. Metastases with increased tracer uptake were clearly visualized at b = 1000 s/mm2 with the exception of mediastinal lymph node metastases in cases of lung cancer. ADC mapping did not improve detection rates. CONCLUSIONS: DWI is a feasible clinical technique, improving the assessment of metastatic spread in routine magnetic resonance imaging examinations.

Morphologic, functional, and metabolic magnetic resonance imaging-guided prostate biopsy in a patient with prior negative transrectal ultrasound-guided biopsies and persistently elevated prostate-specific antigen levels.

A 65-year-old patient was examined with [11C]-choline positron emission tomography-computed tomography and magnetic resonance imaging (MRI) for possible tumor detection after two negative sessions of transrectal ultrasound-guided prostate biopsy and persistently elevated prostate-specific antigen levels for 27 months. Choline positron emission tomography revealed a small and circumscribed pathologic tracer uptake in the right dorsal peripheral gland. Whereas T2-weighted MRI and high b-value diffusion-weighted imaging were able to reproduce this suspicious area, proton MR spectroscopy showed no significant increase of the amplitude of choline-containing compounds. Magnetic resonance imaging-guided prostate biopsy was successfully performed. All specimens taken from the lesion showed a Gleason 5 tubular adenocarcinoma with low proliferative activity.

Fixation devices for whole-body 18F-FDG PET/CT: patient perspectives and technical aspects.

OBJECTIVE: To evaluate the use of a fixation device in whole-body postiron emission tomography/computed tomography (PET/CT). METHODS: Two hundred and thirty patients were prospectively included over a period of 3 months. Different single-phase and multiphase contrast-enhanced PET/CT protocols were used for whole-body examination. An unforced expiration state was applied as breathing protocol for CT examination. Patients were placed on a deflating device (1.0 m x 1.5 m) with arms elevated but supported in order to prevent full extension in shoulders and elbows providing comfortable positioning. Image quality was assessed by means of alignment of the liver quantitatively on co-registered PET/CT images. After the examination, patients were asked to complete a survey on subjective sensations such as pain in different body regions (yes/no). They were asked to give a final evaluation for the whole-body PET/CT examination (comfortable/not comfortable). Additionally, a control group (n=30) was assessed without the aid of additional devices. RESULTS: Examination protocols using the device showed minor misalignment of 5 mm. Different protocols did not reveal significant differences in misalignment. When comparing the control group misalignment was significantly higher with approx. 7 mm. The majority (75%) evaluated the positioning as comfortable despite 46% of the patients in this group feeling more or less severe pain in at least one body region. For controls, misalignment was slightly higher whereas only 39% found the positioning comfortable (chi(2)=13.03; P<0.0005) and 61% reported pain (NS). CONCLUSION: Both the technical aspects and patient evaluations favour the use of the vacuum device in whole-body PET/CT examinations. In particular, in time consuming protocols using multiphase CT examination the fixation device leads to excellent co-registration quality and patient compliance.

Prospective comparison of 18F-fluorodeoxyglucose positron emission tomography/computed tomography and whole-body magnetic resonance imaging in staging of advanced malignant melanoma.

The aim of our study was to compare the overall and site-based accuracy and impact on patient management of positron emission tomography/computed tomography (PET/CT) and whole-body (wb) magnetic resonance imaging (MRI) in staging of advanced melanoma. In a prospective blinded study, 64 patients with American Joint Committee on Cancer (AJCC) stage III/IV melanoma underwent 18F-fluorodeoxyglucose PET/CT and wbMRI. In total 420 lesions were evaluated. The overall accuracy of PET/CT was 86.7% compared to 78.8% for wbMRI (P=0.0007). PET/CT was significantly more accurate in N-staging and detecting of skin and subcutaneous metastases, whereas wbMRI was more sensitive in detecting liver, bone and brain metastases. WbMRI was less sensitive but more specific than PET/CT in classifying pulmonary lesions. In 41 patients (64%) whole-body imaging caused changes of treatment. Whole-body staging of patients with advanced melanoma is most accurate by combining wbPET/CT and organ-specific wbMRI including a brain, liver and bone marrow protocol.

Low dose non-enhanced CT versus standard dose contrast-enhanced CT in combined PET/CT protocols for staging and therapy planning in non-small cell lung cancer.

PURPOSE: To evaluate low dose non-enhanced CT and standard dose contrast-enhanced CT in combined PET/CT protocols for staging and therapy planning of non-small cell lung cancer (NSCLC). METHODS: Retrospective analysis was performed of 50 consecutive patients with proven NSCLC who had been referred for primary staging (n=41) or restaging (n=9). All patients underwent a multi-phase PET/CT consisting of a low dose non-enhanced attenuation scan and an arterial and portal-venous contrast-enhanced CT scan followed by whole-body PET. Fused datasets of non-enhanced and contrast-enhanced PET/CT were compared per patient by using the TNM staging system, and per lesion regarding localisation, characterisation and delineation of tumour lesions. The staging results were validated either by histopathology or by clinical-radiological follow-up for >or=6 months. RESULTS: In 47/50 patients, the results of T staging did not differ between the two PET/CT protocols. Three patients could only be correctly classified as having T4 tumours after contrast application. Regarding N staging, both protocols yielded the same results. In M staging, there was only one patient with an improvement of the results as a result of contrast application. The lesion-based analysis of 92 sites showed no difference in the accuracy of lesion localisation and only one revision of lesion characterisation by contrast-enhanced PET/CT. The assessment of tumour delineation was altered by contrast application in 58/92 sites (p<0.0001). In 10/50 patients, contrast-enhanced PET/CT detected additional clinically important findings. CONCLUSION: In patients with advanced NSCLC, contrast-enhanced CT as part of the PET/CT protocol more accurately assessed the TNM stage in 8% of patients compared with non-contrast PET/CT. However, for planning of 3D conformal radiotherapy and non-conventional surgery, contrast-enhanced PET/CT protocols are indispensable owing to their superiority in precisely defining the tumour extent.

A kinetic model for dynamic [18F]-Fmiso PET data to analyse tumour hypoxia.

A method is presented to identify and quantify hypoxia in human head-and-neck tumours based on dynamic [18F]-Fmiso PET patient data, using a model for the tracer transport. A compartmental model was developed, inspired by recent immunohistochemical investigations with the tracer pimonidazole. In order to take the trapping of the tracer and the diffusion in interstitial space into account, the kinetic model consists of two compartments and a specific input function. This voxel-based data analysis allows us to decompose the time-activity curves (TACs) into their perfusion, diffusion and hypoxia-induced retention components. This characterization ranges from well perfused tumours over diffusion limited hypoxia to strong hypoxia and necrosis. The overall shape of the TAC and the model parameters may point at the structural architecture of the tissue sample. The model addresses the two main problems associated with hypoxia imaging with PET. Firstly, the hypoxic areas are spatially separated from well perfused vessels, causing long diffusion times of the tracer. Secondly, tracer uptake occurs only in viable hypoxic cells, which constitute only a small subpopulation in the presence of necrosis. The resulting parameters such as the concentration of hypoxic cells and the perfusion are displayed in parameter plots ('hypoxia map'). Quantification of hypoxia performed with the presented kinetic model is more reliable than a criterion based on static standardized uptake values (SUV) at an early timepoint, because severely hypoxic/necrotic tissues show low uptake and are thus overlooked by SUV threshold identification. The derived independent measures for perfusion and hypoxia may provide a basis for individually adapted treatment planning.

The benefit of functional-anatomical imaging with [18F]fluorodeoxyglucose utilizing a dual-head coincidence gamma camera with an integrated X-ray transmission system in non-small cell lung cancer.

AIM: To evaluate functional-anatomical imaging with 2-[F]fluoro-2-deoxy-D-glucose (F-FDG) utilizing a dual-head coincidence gamma camera with an integrated X-ray transmission system for attenuation correction, anatomical mapping, and image fusion compared to conventional diagnostics by computed tomography (CT) in non-small cell lung cancer (NSCLC). METHODS: Thirty-five patients with NSCLC underwent FDG imaging of the thoracic area using a dual-head coincidence gamma camera (DHC) with an integrated X-ray transmission system. State-of-the-art CT scans had been performed before. Whole-body dedicated FDG positron emission tomography (PET) was performed immediately prior to DHC. Staging by CT and DHC, and DHC with integrated image fusion (FDHC) were re-evaluated with regard to detectable lesions, correct anatomical diagnoses, and clinical impact. Results of DHC and PET were compared for analysis of limitations of DHC. RESULTS: One hundred and thirteen tumour lesions were identified by CT. DHC detected 128 lesions overall: 102 true positive CT lesions were confirmed, 25 additional lesions were detected which affected staging in eight patients, and one false positive lung lesion did not show up in DHC. Nine CT lesions were missed by DHC (lymph node and lung). PET detected 150 areas of focally enhanced uptake, delivering two false positive results (nuchal muscles, pneumonia). Final evaluation confirmed 148 malignant lesions. Compared to CT, the results of DHC changed staging or treatment in 8/35 patients (23%). Lesion detection by DHC was limited by tumour size and intensity of FDG uptake. Image fusion provided relevant clinical information in 9/35 patients (26%). CONCLUSION: Functional imaging in NSCLC with this dual-head gamma camera is superior to morphological imaging by CT, although inferior to dedicated PET imaging. Combined functional-anatomical imaging has the potential to improve staging and localization procedures before surgery or radiotherapy.

Evaluation of dosimetry of radioiodine therapy in benign and malignant thyroid disorders by means of iodine-124 and PET.

The aim of this study was to evaluate the use of 124I positron emission tomography (PET) to determine the dosimetry of radioiodine therapy in hyperthyroidism and thyroid cancer. Phantom studies to assess the accuracy of PET were performed using an EEC phantom with spheres of different diameters filled with 3-30 MBq of 124I. Patient dosimetry was derived from PET data obtained 1-13 days after simultaneous oral administration of a therapeutic dose of 131I and a diagnostic dose of 124I. The obtained data were compared with findings from intratherapeutic probe measurements and clinical outcome. The phantom studies confirmed that 124I can be quantitated by PET (imprecision < or =10%), and volumetry is feasible for nodules <13 mm (imprecision < or =20%). Any influence of contamination with 123I or the simultaneous administration of 131I on the accuracy of the PET quantification and the probe measurements was ruled out by phantom measurements with solutions of 131I, 124I and 123I in various ratios. In autonomous nodular goitres, radioiodine uptake measured by PET varied from 25.4% to 64.3% and was not significantly different from that obtained by a scintillation probe (24.1%-73.1%, correlation coefficient r=0.91). Comparison of uptake and effective half-life in normal tissue versus autonomous nodules revealed significant differences in uptake but not in effective half-life [uptake 2.0-8.3 kBq/(ml x MBq) in normal tissue vs 12.6-29.3 kBq/(ml x MBq) in nodules; half-life 97.8-156.7 h in normal tissue vs 73.3-192.3 h in nodules]. Calculated radiation doses ranged between 177 and 633 Gy for autonomous nodules and between 47 and 126 Gy for normal tissue. In thyroid cancer patients, doses between 350 and 1,420 Gy were achieved in thyroid remnants and between 70 and 170 Gy in tumour metastases. It is concluded that 124I and PET are suitable for evaluation of the dosimetry of radioiodine therapy in benign and malignant thyroid diseases. The applied technique might be particularly useful for quantitative dose-response studies in radioiodine treatment and further investigations of stunning phenomena.