The integral role of positron-emission tomography (PET) using the glucose analog tracer fluorine-18 fluorodeoxyglucose (FDG) in the staging of non-small cell lung cancer (NSCLC) is well established. Evidence is emerging for the role of PET in response assessment to neoadjuvant therapy, combined-modality therapy, and early detection of recurrence. Here, we review the current literature on these aspects of PET in the management of NSCLC. FDG-PET, particularly integrated 18F-FDG-PET/CT, scans have become a standard test in the staging of local tumor extent, mediastinal lymph node involvement, and distant metastatic disease in NSCLC. 18F-FDG-PET sensitivity is generally superior to computed tomography (CT) scans alone. Local tumor extent and T stage can be more accurately determined with FDG-PET in certain cases, especially in areas of post-obstructive atelectasis or low CT density variation. FDG-PET sensitivity is decreased in tumors <1 cm, at least in part due to respiratory motion. False-negative results can occur in areas of low tumor burden, e.g., small lymph nodes or ground-glass opacities. 18F-FDG-PET-CT nodal staging is more accurate than CT alone, as hilar and mediastinal involvement is often detected first on 18F-FDG-PET scan when CT criteria for malignant involvement are not met. 18F-FDG-PET scans have widely replaced bone scintography for assessing distant metastases, except for the brain, which still warrants dedicated brain imaging. 18F-FDG uptake has also been shown to vary between histologies, with adenocarcinomas generally being less FDG avid than squamous cell carcinomas. 18F-FDG-PET scans are useful to detect recurrences, but are currently not recommended for routine follow-up. Typically, patients are followed with chest CT scans every 3–6 months, using 18F-FDG-PET to evaluate equivocal CT findings. As high 18F-FDG uptake can occur in infectious, inflammatory, and other non-neoplastic conditions, 18F-FDG-PET-positive findings require pathological confirmation in most cases. There is increased interest in the prognostic and predictive role of FDG-PET scans. Studies show that absence of metabolic response to neoadjuvant therapy correlates with poor pathologic response, and a favorable 18F-FDG-PET response appears to be associated with improved survival. Further work is underway to identify subsets of patients that might benefit individualized management based on FDG-PET.
PET; non-small cell lung cancer; staging; response assessment; follow-up
BACKGROUND: A study was undertaken to investigate the accuracy of positron emission tomography (PET) with 2-[18F]-fluoro-2-deoxy-D- glucose (FDG) in the thoracic lymph node staging of non-small cell lung cancer (NSCLC). METHODS: Forty six patients with focal pulmonary tumours who underwent preoperative computed tomographic (CT) and FDG- PET scanning were evaluated retrospectively. Thirty two patients had NSCLC and 14 patients had a benign process. The final diagnosis was established by means of histopathological examination at thoracotomy, and the nodal classification in patients with lung cancer was performed by thorough dissection of the mediastinal nodes at surgery. RESULTS: FDG-PET was 80% sensitive, 100% specific, and 87.5% accurate in staging thoracic lymph nodes in patients with NSCLC, whereas CT scanning was 50% sensitive, 75% specific, and 59.4% accurate. The absence of lymph node tumour involvement was identified by FDG-PET in all 12 patients with NO disease compared with nine by CT scanning. Lymph node metastases were correctly detected by FDG-PET in three of five patients with N1 disease compared with two by CT scanning, in nine of 11 with N2 disease compared with six by CT scanning, an in all four with N3 nodes compared with two by CT scanning. CONCLUSIONS: FDG-PET provides a new and effective method for staging thoracic lymph nodes in patients with lung cancer and is superior to CT scanning in the assessment of hilar and mediastinal nodal metastases. With regard to resectability, FDG-PET could differentiate reliably between patients with N1/N2 disease and those with unresectable N3 disease.
The aim of the study was to assess the interobserver variability in chest computed tomography (CT) and whole body 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography (FDG-PET) screening for distant metastases in head and neck squamous cell carcinoma (HNSCC) patients.
Chest CT and whole body FDG-PET of 69 HNSCC patients with high-risk factors who underwent screening for distant metastases were analyzed. All scans were independently read by two experienced radiologists or nuclear physicians who were blinded to the other examinations and follow-up results.
A kappa of 0.516 was found for assessment of size on CT. Kappa values for origin and susceptibility of 0.406 and 0.512 for CT and 0.834 and 0.939 for PET were found, respectively. The overall conclusions had a kappa of 0.517–0.634 for CT and 0.820–1.000 for PET.
In screening for distant metastases in HNSCC patients with high-risk factors, chest CT readings had a reasonable to substantial agreement, while PET readings showed an almost perfect agreement. These findings suggest that for optimal assessment in clinical practice, PET most often can be scored by one observer, but CT should probably more often be scored by different observers in consensus or combined with PET.
CT; FDG-PET; Interobserver agreement; Distant metastases; Head and neck cancer
To evaluate accuracy and interobserver variability in the assessment of 2-deoxy-2[F-18]fluoro-d-glucose-positron emission tomography (FDG-PET) for detection of recurrent laryngeal carcinoma after radiotherapy.
Eleven experienced nuclear physicians from eight centres assessed 30 FDG-PET scans on the appearance of local recurrence (negative/equivocal/positive). Conservative (equivocal analysed as negative) and sensitive (equivocal analysed as positive) assessment strategies were compared to the reference standard (recurrence within 6months after PET).
Seven patients had proven recurrences. For the conservative and sensitive strategy, the mean sensitivity was 87% and 97%, specificity 81% and 63%, positive predictive values 61% and 46% and negative predictive values 96% and 99%, respectively. Interobserver variability showed a reasonable relation in comparison to the reference standard (kappa = 0.55).
FDG-PET has acceptable interobserver agreement and yields good negative predictive value for detection of recurrent laryngeal carcinoma. It could therefore be used as first diagnostic step and may reduce futile invasive diagnostics.
FDG-PET; Laryngeal carcinoma; Radiotherapy; Interobserver variability; Detection; Local recurrence
Cancer of unknown primary origin (CUP) is an aggressive disease with a poor prognosis. Metastatic brain tumors occur in approximately 15% of all cancer patients. F-18 2′-deoxy-2fluoro-D-glucose (FDG) positron emission tomography (PET) combined with computed tomography (PET/CT) contributes to the evaluation of cancer staging, although the benefits of PET/CT for detection of CUP origins has yet to be determined. In this study, we present a 37-year-old man with a brain tumor detected by magnetic resonance imaging. Surgical biopsy indicated a metastatic undifferentiated carcinoma, while clinical examination and a CT scan did not detect any abnormalities, with the exception of brain metastases. PET/CT did not reveal abnormal FDG uptake. PET/CT revealed abnormal intense FDG uptake in a small nodular lesion in the right lung 1 year following the detection of brain metastasis, and no other abnormal FDG uptake was observed elsewhere in the body. Right upper lobectomy and dissection of mediastinal lymph nodes were performed. The pathological diagnosis was poorly differentiated adenocarcinoma, which was similar to the brain metastatic lesion, and there was no lymph node metastasis. This case revealed an extremely rare lung cancer with primary lesions demonstrated by PET/CT 1 year after the detection of brain metastasis. This case reveals that F-18 FDG PET/CT imaging of CUP origin is capable of positively impacting on the identification of small primary tumor foci.
PET/CT; metastatic brain tumor; lung cancer; unknown primary origin
Background: A study was undertaken to study the effect of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the diagnosis and management of clinically problematic patients with suspected non-small cell lung cancer (NSCLC).
Methods: A prospective before-after study was performed in a cohort of all 164 patients (university/community settings) referred for PET between August 1997 and July 1999. PET was restricted to cases where non-invasive tests had failed to solve clinical problems. The impact on diagnostic understanding and management was assessed using questionnaires (intended treatment without PET, actual treatment choice after PET, post hoc clinical assessment).
Results: Diagnostic problems especially pertained to unclear radiological findings (n=112; 63%), mediastinal staging (n=36; 20%), and distant staging issues (n=16; 9%). PET findings were validated by reviewing medical records. PET had a positive influence on diagnostic understanding in 84%. Improved diagnostic understanding solely based on PET was reported in 26%. According to referring physicians, PET resulted in beneficial change of treatment in 50%. Cancelled surgery was the most frequent change in treatment after PET (35%).
Conclusion: FDG PET applied as "add on" technology in patients with these clinical problems appears to be a clinically useful tool, directly improving treatment choice in 25% of patients. The value of increased confidence induced by PET scanning requires further evaluation.
Positron emission tomography with 2-deoxy-2-[18F]fluoro-d-glucose (FDG-PET) is available for evaluation of patients with melanoma. This study evaluates the potential of FDG-PET to improve on conventional imaging (CI) in patients with stage IV melanoma undergoing metastasectomy.
This was a prospective study comparing radiological evaluation of patients who underwent metastasectomy for palliation or cure. Patients underwent preoperative evaluation by physical examination, CI by computed tomography and/or magnetic resonance imaging, and FDG-PET. Independent observers performed three separate analyses of CI alone, FDG-PET alone, or FDG-PET read with knowledge of CI (FDG-PET + CI). Abnormalities were reported as benign or malignant and assessed by pathologic analysis or by clinical outcome determined by disease progression detected on serial evaluations.
Ninety-four lesions were noted in 18 patients who underwent preoperative assessment, metastasectomy, and long-term follow up (median, 24 months). Lesion-by-lesion analysis for CI demonstrated a sensitivity of 76%, a specificity of 87%, a positive predictive value (PPV) of 86%, and a negative predictive value (NPV) of 76%. FDG-PET demonstrated a sensitivity of 79%, a specificity of 87%, a PPV of 86%, and an NPV of 80%. For FDG-PET + CI, the sensitivity was 88%, specificity was 91%, and PPV and NPV were 91% and 88%, respectively.
Combined use of FDG-PET and CI may be an accurate strategy to identify sites of disease in patients with stage IV melanoma being considered for metastasectomy. Interpreted independently, FDG-PET and CI seemed to be equivalent modalities. FDG-PET + CI had both the highest sensitivity on lesion-by-lesion analysis and the best accuracy on patient-by-patient analysis.
Melanoma; Cancer; FDG-PET; Imaging; Metastasectomy; Surgery
The added value of baseline positron emission tomography (PET) scans in therapy evaluation in malignant lymphoma is unclear. In guidelines, baseline PET is recommended but not mandatory except in lymphoma types with variable fluoro-d-glucose uptake. The aim of the present study was to test the hypothesis that adding baseline PET information decreases false positive readings with posttreatment PET and improves observer agreement.
Forty-four patients (mean age 56 years, standard deviation 14) with malignant lymphoma were included. Two nuclear medicine physicians retrospectively and independently evaluated the posttreatment PET, 3 weeks later followed by paired reading of baseline and posttreatment PET. For each PET, 22 regions were classified as positive, negative, or equivocal, resulting in an overall PET score of positive, unclear, or negative. In case of discrepancies, consensus was reached.
Addition of baseline to posttreatment PET evaluation affected the classification of metabolic response in 34% of malignant lymphoma patients treated with first-line chemotherapy. In one out of seven patients, addition of the baseline PET lead to opposite conclusions (95% confidence interval 4–14). False positivity was reduced by adding the baseline scan information, but the effect on false negativity was similar. In addition, the amount of unclear classifications halved after paired reading. Observer agreement did not improve upon adding the baseline PET data.
Without any other clinical information, pretreatment PET facilitates changes the interpretation of a posttreatment PET in a third of the patients, resulting in both upgrading and downgrading of the posttreatment situation of a malignant lymphoma patient. If these results are confirmed for PET–computed tomography systems, they favor the addition of baseline PET to the current work-up of patients with malignant lymphoma.
FDG PET; Malignant lymphoma; Therapy evaluation; Baseline PET; Hodgkin’s disease; Non-Hodgkin’s lymphoma
There has been an increase in the detection rate of small early lung cancer due to recent improvements in imaging technology. However, conventional imaging modalities such as computed tomography (CT) alone are not capable of differentiating small pulmonary nodules. New modalities such as F-18 2′-deoxy-2fluoro-D-glucose (FDG) positron emission tomography combined with CT (PET/CT) have contributed to the evaluation of lung cancer staging, although the differential diagnosis of pulmonary nodules showing ground-glass opacity (GGO) with PET/CT is controversial. In Japan, cancer screening with whole body FDG-PET has been available for asymptomatic individuals, and it has been reported that a wide variety of cancer types are detectable by FDG-PET at potentially curable stages. We present the case of a 62-year-old male with early lung cancer, which was revealed by repeated health screening. A PET/CT scan revealed definite intense FDG uptake (SUVmax 1.2) in the pulmonary nodules of the right upper lobe, while no definite FDG uptake was observed in the lesion in the previous annual screening. Right upper lobectomy was performed, and the pathological diagnosis was well-differentiated adenocarcinoma. Five-year survival has been noted since the thoracotomy, and the patient is doing well without recurrence. This is a significant case of early lung cancer with GGO lesions, which revealed intense FDG uptake during an annual repeated health screening with FDG-PET/CT.
lung cancer; positron emission tomography/computed tomography; screening; ground-glass opacity
Positron emission tomography (PET) is a non-invasive imaging modality, which is clinically widely used both for diagnosis and accessing therapy response in oncology, cardiology and neurology.
Fusing PET and CT images in a single dataset would be useful for physicians who could read the functional and the anatomical aspects of a disease in a single shot.
The use of fusion software has been replaced in the last few years by integrated PET/CT systems, which combine a PET and a CT scanner in the same gantry. CT images have the double function to correct PET images for attenuation and can fuse with PET for a better visualization and localization of lesions. The use of CT for attenuation correction yields several advantages in terms of accuracy and patient comfort, but can also introduce several artefacts on PET-corrected images.
PET/CT image artefacts are due primarily to metallic implants, respiratory motion, use of contrast media and image truncation. This paper reviews different types artefacts and their correction methods.
PET/CT improves image quality and image accuracy. However, to avoid possible pitfalls the simultaneous display of both Computed Tomography Attenuation Corrected (CTAC) and non corrected PET images, side by side with CT images is strongly recommended.
PET/CT; artefacts; attenuation correction
To evaluate the metabolic changes on 18 F-fluoro-2-deoxyglucose positron emission tomography integrated with computed tomography (18 F-FDG PET-CT) performed before, during and after concurrent chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC); to correlate the metabolic response with the delivered radiation dose and with the clinical outcome.
Twenty-five NSCLC patients candidates for concurrent chemo-radiotherapy underwent 18 F-FDG PET-CT before treatment (pre-RT PET-CT), during the third week (during-RT PET-CT) of chemo-radiotherapy, and 4 weeks from the end of chemo-radiotherapy (post-RT PET-CT). The parameters evaluated were: the maximum standardized uptake value (SUVmax) of the primary tumor, the SUVmax of the lymph nodes, and the Metabolic Tumor Volume (MTV).
SUVmax of the tumor and MTV significantly (p=0.0001, p=0.002, respectively) decreased earlier during the third week of chemo-radiotherapy, with a further reduction 4 weeks from the end of treatment (p<0.0000, p<0.0002, respectively). SUVmax of lymph nodes showed a trend towards a reduction during chemo-radiotherapy (p=0.06) and decreased significantly (p=0.0006) at the end of treatment. There was a significant correlation (r=0.53, p=0.001) between SUVmax of the tumor measured at during-RT PET-CT and the total dose of radiotherapy reached at the moment of the scan. Disease progression free survival was significantly (p=0.01) longer in patients with complete metabolic response measured at post-RT PET-CT.
In patients with locally advanced NSCLC, 18 F-FDG PET-CT performed during and after treatment allows early metabolic modifications to be detected, and for this SUVmax is the more sensitive parameter. Further studies are needed to investigate the correlation between the metabolic modifications during therapy and the clinical outcome in order to optimize the therapeutic strategy. Since the metabolic activity during chemo-radiotherapy correlates with the cumulative dose of fractionated radiotherapy delivered at the moment of the scan, special attention should be paid to methodological aspects, such as the radiation dose reached at the time of PET.
18F-FDG PET-CT; NSCLC; Chemo-radiotherapy; Metabolic response
The most frequently used molecular imaging technique is currently 18F-deoxy-glucose (FDG) positron emission tomography (PET). FDG-PET holds promise in the evaluation of recurrent or residual ovarian cancer when CA125 levels are rising and conventional imaging, such as ultrasound, CT, or MRI, is inconclusive or negative. Recently, integrated PET/CT, in which a full-ring-detector clinical PET scanner and a multidetector helical CT scanner are combined, has enabled the acquisition of both metabolic and anatomic imaging data using one device in a single diagnostic session. This can also provide precise anatomic localization of suspicious areas of increased FDG uptake and rule out false-positive PET findings. FDG-PET/CT is an accurate modality for assessing primary and recurrent ovarian cancer and may affect management. FDG-PET/CT may provide benefits for detection of recurrent of ovarian cancer and improve surgical planning. And FDG-PET has been shown to predict response to neoadjuvant chemotherapy and survival in advanced ovarian cancer. This review focuses on the role of FDG-PET and FDG-PET/CT in the management of patients with ovarian cancer. Recently, we have evaluated 16α-18F-fluoro-17β-estradiol (FES)-PET, which detects estrogen receptors. In a preliminary study we reported that FES-PET provides information useful for assessing ER status in advanced ovarian cancer. This new information may expand treatment choice for such patients.
Although frequently used for tumor surveillance, the sensitivity of carcinoembryonic antigen (CEA) to detect recurrent colorectal cancer (CRC) is not optimal. Fluorine 18-fluoro-2-deoxy-glucose-positron emission tomography (18F FDG-PET) scans promise to improve recurrent CRC detection. We aimed to review PET scans of patients with clinically and/or radiologically suspicious tumor recurrence but normal CEA.
A retrospective review of an electronic database of 308 patients with CRC who had PET scans was performed. Only PET studies of patients with normal CEAs and suspected tumor recurrence who had pathological verification were selected for further analysis. Thirty-nine patients met the inclusion criteria.
PET was positive in 26 patients (67%) and normal in 13 (33%). Histopathologic evidence of tumor recurrence was seen in 27 of the 39 patients (69%). When correlated with histopathology, PET was true positive in 22 patients, false positive in 4, true negative in 8 and false negative in 5. Overall, the accuracy of PET was 76.9%, negative predictive value (NPV) was 61.5%, and positive predictive value (PPV) was 84.6%. PPV value of PET for liver metastases was 88.8% compared to 73.3% for local recurrence. In two patients with confirmed recurrence, CEA became positive 2 months after PET scan indicating earlier detection of disease with PET. The false positive PET findings were mainly in the bowel and were secondary to acute/chronic inflammation and granulation tissue. In 3 patients with false negative PET, histopathology was consistent with mucinous adenocarcinoma.
PET yields high PPV for recurrent CRC, particularly for liver metastases, in spite of normal CEA levels and should be considered early in the evaluation of patients with suspected tumor recurrence.
18Fluoro-2-Deoxy Glucose (18 FDG) positron emission tomography (PET) impacts upon the management of recurrent colorectal cancer (CRC) but is limited by anatomical localisation. The development of integrated positron emission and computerised tomography (PET/CT) yields high anatomical resolution combined with the PET data. We evaluate the added value of PET/CT over PET alone.
Thirty-one consecutive patients had PET/CT for suspected recurrent CRC. Two blinded observers (A and B) reported images from PET alone and from integrated PET/CT. Lesion detection, lesion localisation, diagnostic certainty and impact on surgical management was assessed for each data set and then compared. The minimum clinical follow up was for 8 months (median 9.6 months) and 7 patients had histological confirmation of diagnosis.
Compared to PET alone, PET/CT the percentage of lesions accurately localised increased from 96% to 99% for observer A and 86% to 99% for Observer B. PET/CT increased the number of lesions reported as definitely abnormal or normal from 78% to 95% for Observer A and from 72% to 94% for Observer B. Surgical management was changed in 6 patients (19%). Inter-observer variability was reduced with PET/CT.
PET/CT improves the accuracy of reporting in recurrent colorectal cancer and influences surgical management in a significant proportion of patients when compared to PET only imaging.
PETCT; Advanced colorectal cancer; Surgical management
To compare the interobserver agreement and degree of confidence in anatomical localisation of lesions using 2-[fluorine-18]fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) and 18F-FDG PET alone in patients with head and neck tumours. A prospective study of 24 patients (16 male, eight female, median age 59 years) with head and neck tumours was undertaken. 18F-FDG PET/CT was performed for staging purposes. 2D images were acquired over the head and neck area using a GE Discovery LS™ PET/CT scanner. 18F-FDG PET images were interpreted by three independent observers. The observers were asked to localise abnormal 18F-FDG activity to an anatomical territory and score the degree of confidence in localisation on a scale from 1 to 3 (1=exact region unknown; 2=probable; 3=definite). For all 18F-FDG-avid lesions, standardised uptake values (SUVs) were also calculated. After 3 weeks, the same exercise was carried out using 18F-FDG PET/CT images, where CT and fused volume data were made available to observers. The degree of interobserver agreement was measured in both instances. A total of six primary lesions with abnormal 18F-FDG uptake (SUV range 7.2–22) were identified on 18F-FDG PET alone and on 18F-FDG PET/CT. In all, 15 nonprimary tumour sites were identified with 18F-FDG PET only (SUV range 4.5–11.7), while 17 were identified on 18F-FDG PET/CT. Using 18F-FDG PET only, correct localisation was documented in three of six primary lesions, while 18F-FDG PET/CT correctly identified all primary sites. In nonprimary tumour sites, 18F-FDG PET/CT improved the degree of confidence in anatomical localisation by 51%. Interobserver agreement in assigning primary and nonprimary lesions to anatomical territories was moderate using 18F-FDG PET alone (kappa coefficients of 0.45 and 0.54, respectively), but almost perfect with 18F-FDG PET/CT (kappa coefficients of 0.90 and 0.93, respectively). We conclude that 18F-FDG PET/CT significantly increases interobserver agreement and confidence in disease localisation of 18F-FDG-avid lesions in patients with head and neck cancers.
18F-FDG PET/CT; imaging; head and neck cancers; squamous cell carcinoma
An intracardial electromechanical mapping system has recently been introduced which offers the ability to perform on-line myocardial viability assessment in the catheterisation laboratory. Only a small number of studies have been performed to validate this potentially very useful technique.
We sought to assess the correlation between viability assessment performed with both positron emission tomography (PET) and electromechanical cardiac mapping (EMM) in patients suffering from severe coronary artery disease, since PET is considered the golden standard in myocardial viability assessment.
Patients undergoing both EMM and PET analysis were systematically scanned for viability assessment. EMM analysis was performed for both linear local shortening and unipolar voltage. PET analysis consisted of dipyridamole stress and fluoro-deoxy-d-glucose (FDG) measurements. All data were converted to nine-segment bull's-eye maps to allow comparison. One single operator analysed all the data, blinded for clinical status.
34 patients suffering from severe coronary artery disease underwent both PET and EMM analysis. In total 253 EMM segments had more than four contact points and could be used for analysis. Unipolar voltage showed a trend towards lower values in infarcted segments; however, linear local shortening did not show any correlation.
In this study viability assessment by EMM did not correspond with PET analysis. Although the advantage of having some form of online myocardial assessment is evident, operators should bare in mind that the quantitative EMM measurements are not an absolute substitute for nuclear imaging.
electromechanical cardiac mapping; positron emission tomography; viability assessment
In this study, we investigated the impact of implementation of [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) in daily practice on adherence to mediastinal staging protocols and performance of mediastinoscopy in non–small-cell lung cancer (NSCLC) patients who are possible candidates for surgical resection. Institutional review board approval was obtained.
Patients and Methods
From a nonuniversity teaching hospital and three surrounding community hospitals in Eindhoven, the Netherlands, we studied data from 143 patients with NSCLC who underwent mediastinoscopy and/or thoracotomy in three consecutive periods (1, 0 to 9 months; 2, 10 to 18 months; and 3, 19 to 31 months) after introduction of PET. Mediastinoscopy was indicated in case of enlarged and/or PET-positive nodes. Adherence to these surgical mediastinal staging guidelines and the performance of PET and mediastinoscopy were investigated and compared between the three periods and with our previous study before introduction of PET.
Results and Conclusion
Guidelines for indicating mediastinoscopy were adequately followed in significantly more instances after introduction of PET (80%), compared with the period before PET (66%). Optimal yield (lymph node stations 4, right and left, and 7) of mediastinoscopy (in 27% of patients) was not significantly different from the period before PET (39% of patients). Compared with the historical data, the percentage of positive mediastinoscopies increased from 15.5 to 17.6 (not significant). We found no significant differences between the three consecutive periods with regard to adequacy of indicating and performance of mediastinoscopy. After introduction of PET, adherence to staging guidelines with respect to mediastinoscopy improved. Although fewer mediastinoscopies had an optimal yield, more proved to be positive for metastases. Nevertheless, when a mediastinoscopy is indicated, surgeons must be encouraged to reach an optimal yield because PET positive nodes might be false negative. This occurred in 5% to 6% of all patients.
The purpose of this study is to compare the performance of multidetector computed tomography (CT) and positron emission tomography/CT (PET/CT) with [18F]fluorodeoxyglucose in the diagnosis of multiple solitary lung nodules in 14 consecutive patients with suspicious lung cancer. CT and PET/CT findings were reviewed by a radiologist and nuclear medicine physician, respectively, blinded to the pathological diagnoses of lung cancer, considering nodule size, shape, and location (CT) and maximum standardized uptake value normalized to body weight (SUVbw max). Nodules were judged malignant or benign. The sensitivity, specificity, and accuracy of the two techniques were compared. CT had a sensitivity, specificity, and accuracy of 93.7, 86.7, and 90.3%, respectively, whereas PET/CT had a sensitivity, specificity, and accuracy of 75, 100, and 87.1%, respectively. Clinical management would have been erroneous in two patients by CT alone and in four patients by PET/CT alone. In one patient, the two techniques misdiagnosed the nodules (2 CT and 1 PET/CT). CT and PET/CT have complimentary roles in characterization of multiple solitary pulmonary nodules. Small nodules are poorly characterized by CT, and small-sized low-SUV malignant nodules are difficult to detect with PET/CT.
We have previously developed 11C-erlotinib as a new positron emission tomography (PET) tracer and shown that it accumulates in epidermal growth factor receptor (EGFR)-positive lung cancer xenografts in mice. Here, we present a study in patients with non-small cell lung cancer (NSCLC) investigating the feasibility of 11C-erlotinib PET as a potential method for the identification of lung tumours accumulating erlotinib.
Thirteen patients with NSCLC destined for erlotinib treatment were examined by contrast-enhanced computed tomography (CT), 11C-erlotinib PET/low-dose CT and 18F-fluoro-2-deoxy--glucose (18F-FDG) PET/low-dose CT before start of the erlotinib treatment. After 12 weeks treatment, they were examined by 18F-FDG PET/contrast-enhanced CT for the assessment of clinical response.
Of the 13 patients included, 4 accumulated 11C-erlotinib in one or more of their lung tumours or lymph-node metastases. Moreover, 11C-erlotinib PET/CT identified lesions that were not visible on 18F-FDG PET/CT. Of the four patients with accumulation of 11C-erlotinib, one died before follow-up, whereas the other three showed a positive response to erlotinib treatment. Three of the nine patients with no accumulation died before follow-up, four showed progressive disease while two had stable disease after 12 weeks of treatment.
Our data show a potential for 11C-erlotinib PET/CT for visualizing NSCLC lung tumours, including lymph nodes not identified by 18F-FDG PET/CT. Large clinical studies are now needed to explore to which extent pre-treatment 11C-erlotinib PET/CT can predict erlotinib treatment response.
erlotinib; EGFR; tarceva; lung cancer; PET imaging
Mediastinal masses include a wide variety of tumours and remain an interesting diagnostic challenge for radiologist. We performed positron emission tomography (PET) studies of primary mediastinal tumours in order to predict the malignancy of these tumours preoperatively. Twenty-two patients with primary mediastinal tumours were studied with PET using 2-deoxy-2-[18F]fluoro-D-glucose (FDG). The histological findings of surgical pathology or biopsy, or mediastinoscopy were compared with those of computerised tomography (CT) and PET. PET images were evaluated semiquantitatively using the differential uptake ratio (DUR). Increased FDG uptake was observed in nine of ten patients with malignant tumours, including thymic carcinomas, lymphomas, invasive thymomas and a case of sarcoidosis. A moderate level of FDG uptake was found in a myeloma, non-invasive thymomas, and a schwannoma, whereas a low uptake was observed in a teratoma and various benign cysts. The mean FDG uptake of malignant tumours was significantly higher than that of benign tumours. Both thymic cancer and invasive thymoma showed a high FDG uptake. CT examination resulted in three false-negative and two false-positive cases when used in predicting tumour invasion, while PET was associated with a false-positive and a false-negative case. In conclusion, the use of FDG with PET is clinically helpful in evaluating the malignant nature of primary mediastinal tumours. Our results also suggest that a high FDG uptake reflects the invasiveness of malignant nature of thymic tumours.
In the diagnosis of malignant lymph nodes (LNs) and staging of lung cancer, sampling of mediastinal and hilar LNs is essential. Mediastinoscopy is known as the gold standard. Convex probe (CP) endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) is a noninvasive and highly sensitive diagnostic method in mediastinal and hilar LN sampling.
Evaluating the role of CP-EBUS-guided TBNA in the diagnosis of mediastinal and hilar LNs suspicious of malignancy.
Patients and Methods
One hundred twenty patients with a known lung malignancy or hilar/mediastinal LNs detected by thoracic computed tomography (CT) and/or positron emission tomography (PET)-CT suspicious for malignancy were included in this prospective study. The procedure was performed by Olympus 7.5 MHz CP endoscope and EU C2000 processor by the oral route under topical anesthesia and conscious sedation. After visualization of LNs, their dimensions were recorded. Aspiration was considered as “insufficient” if there were inadequate lymphocytes on the smears. Diagnosis of “malignancy” on cytologic examination was considered as the “final diagnosis”. If diagnosis was negative for malignancy, more invasive procedures were performed to confirm the diagnosis.
Twenty four females and 96 male patients (mean age, 57.8 ± 9.1) were included. A total of 177 LN stations were aspirated in 120 patients. In 82 patients, the diagnosis was malignant by EBUS-guided TBNA and in the remaining 38; the diagnosis was established by further invasive procedures. Of the 38 EBUS-guided TBNA negative patients, 28 were diagnosed as non-malignant and 10 were malignant. The sensitivity, diagnostic accuracy and negative predictive value of CP EBUS-guided TBNA were 89.1%, 91.6% and 73.6%, respectively. No major complications were seen.
As an alternative method to mediastinoscopy, EBUS-guided TBNA is a safe and noninvasive procedure with high sensitivity in the diagnosis of malignant mediastinal LNs.
Ultrasonography; Lung Cancer; Mediastinal Neoplasms; Lymph Nodes
Positron emission tomography (PET) may be useful for defining the gross tumour volume for radiation treatment planning and for response monitoring of non-small cell lung cancer (NSCLC) patients. The purpose of this study was to compare tumour sizes obtained from CT- and various more commonly available PET-based tumour delineation methods to pathology findings.
Retrospective non-respiratory gated whole body [18F]-fluoro-2-deoxy-D-glucose PET/CT studies from 19 NSCLC patients were used. Several (semi-)automatic PET-based tumour delineation methods and manual CT-based delineation were used to assess the maximum tumour diameter.
50%, adaptive 41% threshold-based and contrast-oriented delineation methods showed good agreement with pathology after removing two outliers (R2=0.82). An absolute SUV threshold of 2.5 also showed a good agreement with pathology after the removal of 5 outliers (R2: 0.79), but showed a significant overestimation in the maximum diameter (19.8 mm, p<0.05). Adaptive 50%, relative threshold level and gradient-based methods did not show any outliers, provided only small, non-significant differences in maximum tumour diameter (<4.7 mm, p>0.10), and showed fair correlation (R2>0.62) with pathology. Although adaptive 70% threshold-based methods showed underestimation compared to pathology (36%), it provided the best precision (SD: 14%) together with good correlation (R2=0.81). Good correlation between CT delineation and pathology was observed (R2=0.77). However, CT delineation showed a significant overestimation compared with pathology (3.8 mm, p<0.05).
PET-based tumour delineation methods provided tumour sizes in agreement with pathology and may therefore be useful to define the (metabolically most) active part of the tumour for radiotherapy and response monitoring purposes.
Tumour delineation; Tumour diameter; FDG PET; Non-small cell lung cancer
Prostate cancer (PCa) is the second leading cause of cancer death among men in the United States. Positron emission tomography (PET), a non-invasive, sensitive, and quantitative imaging technique, can facilitate personalized management of PCa patients. There are two critical needs for PET imaging of PCa, early detection of primary lesions and accurate imaging of PCa bone metastasis, the predominant cause of death in PCa. Since the most widely used PET tracer in the clinic, 18F-fluoro-2-deoxy-2-D-glucose (18F-FDG), does not meet these needs, a wide variety of PET tracers have been developed for PCa imaging which span an enormous size range from small molecules to intact antibodies. In this review, we will first summarize small molecule-based PET tracers for PCa imaging, which measure certain biological events such as cell membrane metabolism, fatty acid synthesis, and receptor expression. Next, we will discuss radiolabeled amino acid derivatives (e.g. methionine, leucine, tryptophan, and cysteine analogs), which are primarily based on the increased amino acid transport of PCa cells. Peptide-based tracers for PET imaging of PCa, mostly based on the bombesin peptide and its derivatives which bind to the gastrin-releasing peptide receptor, will then be presented in detail. We will also cover radiolabeled antibodies and antibody fragments (e.g. diabodies and minibodies) for PET imaging of PCa, targeting integrin αvβ3, EphA2, the epidermal growth factor receptor, or the prostate stem cell antigen. Lastly, we will identify future directions for the development of novel PET tracers for PCa imaging, which may eventually lead to personalized management of PCa patients.
Molecular imaging; prostate cancer; positron emission tomography (PET); peptide; antibody
The increasing interest in combined positron emission tomography (PET) and computed tomography (CT) to guide lung cancer radiation therapy planning has been well documented. Motion management strategies during treatment simulation PET/CT imaging and treatment delivery have been proposed to improve the precision and accuracy of radiotherapy. In light of these research advances, why has translation of motion-managed PET/CT to clinical radiotherapy been slow and infrequent? Solutions to this problem are as complex as they are numerous, driven by large inter-patient variability in tumor motion trajectories across a highly heterogeneous population. Such variation dictates a comprehensive and patient-specific incorporation of motion management strategies into PET/CT-guided radiotherapy rather than a one-size-fits-all tactic. This review summarizes challenges and opportunities for clinical translation of advances in PET/CT-guided radiotherapy, as well as in respiratory motion-managed radiotherapy of lung cancer. These two concepts are then integrated into proposed patient-specific workflows that span classification schemes, PET/CT image formation, treatment planning, and adaptive image-guided radiotherapy delivery techniques.
PET; FDG; Respiratory gating; Respiratory tracking; IMRT; IGRT; Adaptive radiotherapy
We prospectively investigated using advanced magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) to identify radiological biomarkers for treatment response in patients receiving preoperative systemic therapy (PST) for locally advanced breast cancer. Patients with a stage II or III breast cancer receiving PST were selected and underwent positron emission tomography (PET), magnetic resonance imaging (MRI), and breast biopsies at baseline and after the first cycle of PST (days 7–8) during the full course of treatment. PET/CT was acquired after injection of 2-deoxy-2-[18F]-fluoro-D-glucose (18FDG, 0.22 mCi/kg) and quantified with standardized uptake value assessment (SUV). Diagnostic breast MRI and sodium (23Na) was acquired at 1.5 T. Total tissue sodium concentration (TSC), response criteria in solid tumors (RECIST), and volumes were quantified. Treatment response was determined by pathological assessment at surgery. Immunohistochemistry values of the proliferative index (Ki-67) were performed on biopsy specimens. Six of nineteen eligible women (43 ± 11 years) who received PST underwent radiological imaging of 18FDG-PET/CT and MRI for at least two cycles of treatment. Five patients had a pathological partial response (pPR) and one had pathological non-response (pNR). TSC decreased 21% in responders with increases in the non-responder (P = 0.03). Greater reduction in SUV was observed in responders (38%) compared to the non-responder (22%; P = 0.03). MRI volumes decreased after cycle 1 by 42% (responders) and 35% (non-responder; P = 0.11). Proliferation index Ki-67 declined in responders in the first cycle (median = 47%, range = 29–20%), but increased (4%) in the non-responder. Significant decreases in TSC, SUV, and Ki-67 were observed in responders with increases in TSC and Ki-67 in non-responders. Our results demonstrate the feasibility of using multi-modality proton, 23Na MRI, and PET/CT metrics as radiological biomarkers for monitoring response to PST in patients with operable breast cancer.
Breast; Magnetic resonance imaging; Sodium 23Na MRI; PET; PET/CT; Response; Cancer