Serial positron emission tomography scans following radiation therapy of patients with head and neck cancer.

BACKGROUND: A single institution study was undertaken to evaluate the role of positron emission tomography (PET) scans with fluorodeoxyglucose (FDG) prior to radiation and following radiation. METHODS: Forty-five patients with head and neck cancers were evaluated with FDG-PET scans as well as either CT or MRI prior to treatment with definitive radiation (RT). These same scans were obtained following completion of RT at 1 month (36 patients), 4 months (28 patients), 12 months (19 patients), and 24 months (15 patients). Standard uptake values (SUV) normalized for blood glucose and lean body mass were calculated on the initial and 1-month post-treatment PET scans. RESULTS: Fifteen patients are alive without evidence of disease at 24 to 52 months following RT. Initial SUVs were calculated on the primary tumor site and ranged from 2.5 to 28.5. These values did not have any correlation with local control when examined for the entire group, primary site, or T stage. One-month post-RT SUV ranged from 1.8 to 6.24. Of the 36 1-month post-RT PET scans, six were interpreted as positive for residual disease and were confirmed by biopsy. Four of the five scans, which were interpreted as equivocal, were positive on biopsy. Seven of the 25 scans, which were interpreted as negative for tumor, were positive on biopsy. Four-month scans were more accurate for disease with disease noted in 0 of 18 negative scans, 6 of 7 positive scans, and 2 of 3 equivocal scans. CONCLUSIONS: PET is useful for initial imaging of head and neck cancers. SUV does not appear to be useful for predicting outcome following treatment with RT. One-month post-RT scans were inaccurate for predicting the presence of cancer. Four-month post-RT scans were a better predictor for the presence of cancer.

Hypersexuality and hemiballism due to subthalamic infarction.

OBJECTIVE: A 70-year-old right-handed man presented with a subthalamic infarction followed by persistent hypersexuality and hemiballism. A lacunar infarction 1 cm in diameter was observed on magnetic resonance imaging. We hypothesized that metabolic abnormalities would be detected in cortical areas related to his neurobehavioral symptoms. BACKGROUND: Statistical validation of the regional metabolic changes that may relate to neuropsychiatric symptoms has been elusive. Relating metabolic changes to neuropsychiatric symptoms is especially important in unique neurobehavioral cases. METHOD: Quantitative fluorodeoxyglucose positron emission tomography was obtained for a single-subject comparison with scans from 60 healthy subjects. RESULTS: Substantial glucose hypometabolism (p <0.001, uncorrected; [df = 56]) was identified in the subthalamic nucleus at the site of the lacunar infarction. Hypermetabolism (p <0.01) was identified within the basal forebrain and temporal lobes, anterior cingulate and medial prefrontal cortices (areas previously associated with hypersexuality), and striatum (p <0.001) ipsilateral to the stroke (areas known to relate to hemiballism). CONCLUSIONS: Single-subject statistical parametric mapping may improve our understanding of unique neurobehavioral cases.

Cortical activity related to accuracy of letter recognition.

Previous imaging and neurophysiological studies have suggested that the posterior inferior temporal region participates in tasks requiring the recognition of objects, including faces, words, and letters; however, the relationship between accuracy of recognition and activity in that region has not been systematically investigated. In this study, positron emission tomography was used to estimate glucose metabolism in 60 normal adults performing a computer-generated letter-recognition task. Both a region of interest and a voxel-based method of analysis, with subject state and trait variables statistically controlled, found task accuracy to be: (1) negatively related to metabolism in the left ventrolateral inferior temporal occipital cortex (Brodmann's area 37, or ventrolateral BA 37) and (2) positively related to metabolism in a region of the right ventrolateral frontal cortex (Brodmann's areas 47 and 11, or right BA 47/11). Left ventrolateral BA 37 was significantly related both to hits and to false alarms, whereas the right BA 47/11 finding was related only to false alarms. The results were taken as supporting an automaticity mechanism for left ventrolateral BA 37, whereby task accuracy was associated with automatic letter recognition and in turn to reduced metabolism in this extrastriate area. The right BA 47/11 finding was interpreted as reflecting a separate component of task accuracy, associated with selectivity of attention broadly and with inhibition of erroneous responding in particular. The findings are interpreted as supporting the need for control of variance due to subject and task variables, not only in correlational but also in subtraction designs.

FDG PET evaluation of head and neck cancer: value of imaging the thorax.

BACKGROUND: Patients with primary tumors of the head and neck have been reported to have a high rate of synchronous primary tumors of the upper aerodigestive tract. This study was performed to determine whether inclusion of the thorax in the scan volume would be diagnostically useful for positron emission tomography (PET) with [F-18] fluorodeoxy-D-glucose (FDG) in patients with primary tumors of the head and neck. METHODS: FDG PET scans from the midcranium to the diaphragm were obtained on 56 patients with a variety of head and neck tumors on initial examination before definitive therapy. PET findings in the chest were correlated with results of all other imaging studies, biopsy results, and clinical follow-up. RESULTS: In nine studies (16%), areas of increased FDG uptake in the chest were seen and were judged to be tumors. Six of these probably were false-positive results, although one of these six may have been unconfirmed true positives. Of the three confirmed true-positive studies, two were obvious from other routine studies. In only one case did the PET study reveal a significant lesion not found by means of routine evaluation, resulting in a case-finding yield of 2%. If the unconfirmed possible true-positive results are included, the case-finding yield increases to 4%. CONCLUSIONS: No compelling indication was seen for including the chest in PET studies of patients with head and neck cancer.

Occult primary tumors of the head and neck: lack of benefit from positron emission tomography imaging with 2-[F-18]fluoro-2-deoxy-D-glucose.

BACKGROUND: Patients who present with squamous cell carcinoma metastatic to cervical lymph nodes and no clinically apparent primary site present a therapeutic dilemma. Positron emission tomography imaging with 2-[F-18]fluoro-2-deoxy-D-glucose (FDG-PET) has been shown to be useful for the examination of known primary tumors. This study was undertaken to determine whether FDG-PET imaging improves detection of occult primary tumors in patients with metastatic squamous cell carcinoma in the lymph nodes of the head and neck. METHODS: Thirteen patients with pathology proven cervical lymph node metastases from clinically occult primary squamous cell carcinomas were evaluated prospectively with FDG-PET, in addition to standard clinical and radiographic techniques, as part of their pretreatment diagnostic evaluation. Direct panendoscopy and biopsy were performed on all patients in an attempt to detect primary tumor sites and to characterize them histologically. RESULTS: A primary squamous cell carcinoma was confirmed after panendoscopy and biopsy in 3 of the 13 patients. The site of the primary tumor was correctly identified with FDG-PET in only one of these three patients. The FDG-PET study suggested a primary tumor location where no tumor was found in 6 of 13 patients; for 5 other of the 13 patients, the FDG-PET results were negative and no primary was found. No primary tumor locations were identified by computed tomography, magnetic resonance imaging, or direct panendoscopy. FDG-PET imaging correctly detected the location of the primary tumor in 1 patient (8%) and provided apparent false-positive results for 6 (46%) of the 13 patients. CONCLUSIONS: FDG-PET imaging did not significantly improve detection of unknown primary squamous cell carcinomas in patients with metastases to lymph nodes of the neck. A high percentage of results were apparent false-positive.

PET scanning in head and neck oncology: a review.

BACKGROUND: The objective of this study was to review and describe the usage of fluorine-labeled deoxyglucose (FDG) and positron emission tomography (PET) in the diagnosis and management of head and neck cancer. METHODS: Several prospective series,-including 159 newly diagnosed and previously untreated and 23 previously irradiated head and neck squamous cell carcinoma patients initially seen at the Wake Forest University Medical Center and evaluated by clinical examination, conventional computed tomography/ magnetic resonance imaging (CT/MRI) scans, PET scans, and histopathologic studies,-were reviewed and the findings summarized for comparison of the correct differentiation of primary and metastatic cancers and for postirradiation tumor clearance in a subsegment of those cases. RESULTS: Positron emission tomography scanning using a fluorine-labeled deoxyglucose (FDG) radiotracer proved as reliable as conventional scanning for primary and metastatic tumor identification. Compared with clinical examination, PET was better for identification of nodal metastatic tumors but poorer for small primary tumors. For previously irradiated patients treated at least 4 months before the test, PET scanning was clearly superior to clinical examination and conventional imaging in differentiating tumor recurrence from soft-tissue irradiation effects. CONCLUSIONS: Fluorine-labeled deoxyglucose-PET scanning is comparable to conventional imaging of head and neck cancers in detecting primary and metastatic carcinoma. Lack of anatomic detail remains its major drawback. Currently, its greatest role is in the evaluation of the postradiotherapy patient.

Laryngeal radionecrosis versus recurrent cancer: a clinical approach.

A group of 38 patients was studied by positron emission tomography utilizing fluorine18-labeled deoxyglucose (FDG-PET) scanning to examine the ability to differentiate postirradiation laryngeal recurrent cancer from radionecrosis. The resulting 79% correct diagnosis showed the technique to be far superior to conventional computed tomography scanning (61%) and clinical examination (43%). An algorithmic approach to evaluating and treating patients with radionecrosis and/or recurrent cancer by utilizing FDG-PET scanning is presented.

FDG PET in head and neck cancer.

In our extensive experience with FDG PET imaging in head and neck cancer, we have found the technique to be of high accuracy but of limited usefulness. This seeming paradox arises from several causes. Competing techniques such as CT, MR imaging, and even clinical examination already have good accuracy. In addition, high-resolution studies such as CT and MR imaging provide information required for treatment planning that is unavailable from FDG PET images. The high cost of FDG PET militates against its use in this setting, in which only a small marginal gain can be expected. In the special problem areas in which FDG PET might be expected to offer unique advantages, such as screening for second primary lesions, searching for unknown primary lesions, or differentiating benign salivary rumors from malignant lesions, the results of FDG PET have been disappointedly poor. Of these special problem areas, only the question of accuracy in finding occult primary lesions appears unresolved and in need of further study. The single application in which FDG PET appears to be advantageous is the posttherapy setting. In this setting, the technique is definitely superior to alternative methods of determining tumor recurrence and differentiating posttherapy sequelae such as radiation necrosis from tumor recurrence. We believe that considerable opportunity remains for further research on the use of FDG PET in head and neck cancer. Other agents such as 11C-methionine for example, might improve the diagnostic accuracy of FDG PET in some of the problem areas that we have identified, such as the early postirradiation period. We currently have such a study under way. Also, because FDG PET offers a unique way to measure tumor metabolism, further investigation of the use of FDG PET tracers to evaluate various biologic parameters such as proliferation rates or tumor hypoxia are needed. Such studies could provide a noninvasive technique to identify which fractionation schemes or combinations of therapy might be useful for individual patients. A final caveat is in order. Although our findings of the usefulness (and lack thereof) of FDG PET in head and neck cancer may be disappointing to many, these results should not be generalized to other applications of FDG PET in oncology. Each tumor type and setting presents its own specific problems, and in some instances FDG PET offers unique advantages over other imaging techniques. A good example is the setting of primary lung cancer, in which FDG PET appears clearly superior to all other methods of pretherapy screening [19-20].

Can positron emission tomography distinguish tumor recurrence from irradiation sequelae in patients treated for larynx cancer?

PURPOSE: Distinguishing persistent or recurrent tumor from post-radiation edema or soft-tissue/cartilage necrosis in patients treated for carcinoma of the larynx can be difficult. Because recurrent tumor is often submucosal, multiple deep biopsies may be necessary before a diagnosis can be established. Positron emission tomography with F-18 fluorodeoxyglucose was studied for its ability to aid in this problem. PATIENTS AND METHODS: FDG PET scans were performed on 31 patients who were suspected of having persistent or recurrent tumor after radiation treatment for carcinoma of the larynx. Patients underwent thorough history and physical examinations, scans with computed tomography (23 patients), and pathological evaluation when indicated. PET scans were interpreted by each of the two radiologists, who were blinded to patient outcome and the other's report. RESULTS: The time between completion of radiation treatment and positron emission tomography examination ranged from 2 to 61 months with a median of 6 months. Fifteen patients had pathological evidence of tumor in the larynx, while 16 have remained without evidence of disease. The overall sensitivity and specificity of the positron emission tomography interpretations were 80% and 81%, respectively. The sensitivity and specificity of the computed tomography scan interpretations were 58% and 100%, respectively. Of the 23 patients with computed tomography scans, eight patients acquired useful information from the positron emission tomography, three patients had incorrect positron emission tomography interpretations and correct computed tomography interpretations, and one patient had positive tumor despite a negative positron emission tomography and computed tomography. DISCUSSION: Positron emission tomography is useful in distinguishing benign from malignant changes in the larynx after radiation treatment. This noninvasive technique can supplement information provided by computed tomography scans. It is reasonable to delay biopsy, which could traumatize radiation-damaged tissues and precipitate necrosis, for those patients with negative positron emission tomography scans who have clinical signs and symptoms associated with recurrence.

Intermodality, retrospective image registration in the thorax.

UNLABELLED: The purpose of this study was to develop an accurate, retrospectively applicable procedure for registering thoracic studies from different modalities in a short amount of time and with minimal operator intervention. METHODS: CT and PET studies were acquired from six patients. The pleural surfaces in both image sets were determined by segmenting based on 50% of the maximum soft-tissue value in the study. These surfaces were converted into three-dimensional volumes and used to register the CT and PET studies in three dimensions using a sum of least squares fitting approach. The registered PET study was then displayed in a hot metal scale overlayed on top of the gray scale CT study. The accuracy of the fit was evaluated through a phantom study and preliminary clinical evaluation. RESULTS: A phantom study was performed to determine the limits of this technique. The accuracy was determined to be less than 2.3 mm in the x and y direction and 3 mm in the z direction. Preliminary clinical evaluation was also performed with encouraging results. CONCLUSION: This technique accurately registers PET and CT images of the thorax, retrospectively, without the need for external fiducial markers or other a priori action.

Mediastinal staging of non-small-cell lung cancer with positron emission tomography.

To determine the usefulness of positron emission tomography with fluoro-2-deoxyglucose (PET-FDG) in assessing mediastinal disease in patients with non-small-cell lung cancer (NSCLC) and to compare its yield to that of computed tomography (CT), we performed a prospective consecutive sample investigation in a university hospital and its related clinics. In 30 patients with NSCLC with clinical stage I (T1-2, NO, MO) disease, we compared the results of chest CT and PET-FDG with the findings at surgical exploration of the mediastinum. Seven (77%) of nine patients with surgically proven mediastinal metastasis were identified by the PET-FDG results, with four false-positives in 21 patients with negative lymph node dissections (p = 0.004). Using the results of pathologic examination of mediastinal lymph nodes as the criterion standard, the diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for PET-FDG imaging of mediastinal metastases were 78%, 81%, 80%, 64%, and 89%, respectively. The sensitivity, specificity, accuracy, PPV, and NPV for chest CT in the detection of mediastinal metastasis were 56%, 86%, 77%, 63%, and 87%, respectively. CT and PET-FDG results agreed in 21 patients. The diagnostic accuracy of the combined imaging modalities was 90%. We concluded that mediastinal uptake of FDG correlates with the extent of mediastinal involvement of NSCLC and may contribute to preoperative staging. PET-FDG imaging complements chest CT in the noninvasive evaluation of NSCLC, and strategies for its use merit further investigation.

Preoperative identification of benign versus malignant parotid masses: a comparative study including positron emission tomography.

Various diagnostic tools were used in 26 patients with parotid masses to determine their value in preoperative malignant or benign categorization. These tools were positron emission tomography (PET), clinical examination, fine-needle aspiration biopsy (FNAB), computed tomography (CT), and magnetic resonance imaging (MRI). PET identified all 26 lesions and all 12 malignant lesions, but made the correct categorization in only 69% of cases. Thus, it was not as good as the more conventional diagnostic methods, their correct categorizations being 85% (clinical), 87% (CT/MRI), and 78% (FNAB) in the same patients.

A comparative diagnostic study of head and neck nodal metastases using positron emission tomography.

A prospective study was conducted to compare the accuracy of clinical examination, computed tomography (CT), and positron emission tomography (PET) in identifying head and neck squamous cell carcinoma metastatic to cervical lymph nodes. The findings in the necks of 49 patients evaluated by clinical examination and CT were compared to the findings in the same necks by PET, a newly available metabolic imaging modality. Pathology specimens were available for 45 of the necks. The findings of PET and CT correlated in 84% of cases. In the cases that did not correlate, CT proved correct in four of five cases. PET (82%) and CT (84%) were comparable and were both better than clinical examination (71%) in correctly identifying the presence or absence of metastatic disease.

Positron emission tomography in the evaluation of laryngeal carcinoma.

Positron emission tomography (PET) is a relatively new radiologic imaging technique based on glucose analog uptake and metabolism in tumor tissue. In this study, PET was used in evaluating 38 patients with laryngeal cancer. Twenty-five patients were examined with PET prior to treatment to study the reliability of PET in identifying the primary tumor and assessing regional nodal status; 13 patients who had previously received irradiation with curative intent and who represented differential diagnostic problems were imaged to differentiate between irradiation effects and recurrent or residual cancer. Findings for both groups were compared to results of clinical evaluation and those of computed tomography (CT) and magnetic resonance imaging (MRI). The PET results were essentially identical to those of CT, MRI, and clinical evaluation in identifying metastatic lesions (82% correct), and were as reliable as CT and MRI for correctly identifying primary tumors (88%). Positron emission tomography was most helpful in differentiating recurrent tumor from postirradiation tissue sequelae. However, its lack of anatomic detail made PET less valuable for primary staging and therapeutic planning. It may enhance the diagnostic accuracy of CT and MRI where anatomic distortions occur or where diagnostic criteria for CT and MRI are ambiguous.

Digital clubbing. Demonstration with positron emission tomography.

Digital clubbing is a classic cutaneous manifestation of pulmonary disease, but its mechanism is unknown. We describe a patient with lung cancer and clubbing in whom positron emission tomography (PET) demonstrated, for the first time, that increased glucose metabolism occurs at the nailbed. PET may contribute to future investigations of digital clubbing.

Evaluation of emission-transmission registration in thoracic PET.

UNLABELLED: The intent of this investigation was to quantitate the amount of misregistration between PET emission and transmission scans of the thorax that occurs in a normal clinical environment. METHODS: The data from 17 FDG myocardial studies were evaluated. Prior to injection, a transmission study was acquired for 15 min using a 68Ge/68Ga ring source. The location of the cross-hairs from a laser alignment system was marked on the patient who was then removed from the scanner and injected with 10 mCi of FDG. After 45 min, the patient was placed back on the table and repositioned with the previously placed marks and a 15-min emission scan was acquired. The outline of the lungs on both the transmission and emission images was manually segmented. Both attenuation-corrected and noncorrected emission images were evaluated and the one that provided clearer visualization of the outline of the lungs was chosen for segmentation. The segmented contours of the transmission and emission scans were then registered with the method described by Pelizzari et al. using the transmission image as the "head" and the emission image as the "hat." The allowable transformations were x and y shifts and rotation in the transverse plane. RESULTS: Shifts in the x-axis averaged 2.4 mm (range: 0.2-7.3 mm, 80% less than 3.3 mm) with shifts in the y-axis averaging 2.6 mm (range: 0.1-8.7 mm, 80% less than 2.4 mm) and rotations in the transverse plane averaging 1.6 degrees (range: 0.2 to 5.1 degrees, 80% less than 2.4 degrees). A phantom study indicated that the accuracy of this method of evaluating misregistration was 2.35 mm and 1.81 mm in the x and y directions, respectively. CONCLUSION: Our preliminary evaluation indicates that careful application of laser alignment is an adequate method of registration in most cases.

Positron emission tomography of patients with head and neck carcinoma before and after high dose irradiation.

BACKGROUND: Positron emission tomography (PET) with labeled fluorodeoxyglucose (FDG) demonstrates increased tracer uptake in many neoplasms. This study was undertaken to define the patterns of FDG uptake in head and neck neoplasms before and after high dose irradiation. METHODS: Twenty-five patients were evaluated prospectively with PET and standard clinical and radiographic techniques before and after irradiation. RESULTS: Twenty-seven primary sites were confirmed pathologically in 23 patients and included the nasopharynx (four lesions), oropharynx (14 lesions), larynx (five lesions), oral cavity (two lesions), and paranasal sinuses (two lesions). Two patients had unknown primary sites. Twenty-four of 27 primary sites correlated with areas of increased tracer uptake on PET scans. Five patients had increased uptake in cervical lymph nodes that were uninvolved by radiographic or clinical criteria. Positron emission tomography seemed to be able to differentiate tumor activity from fluid-filled sinuses in two patients with paranasal sinus tumors. In two patients with unknown primary sites, increased uptake in the base of tongue after PET suggested occult primary sites. Positron emission tomography scans obtained 1 month after high dose irradiation (RT) indicated decreased levels of FDG uptake in all patients' tumors. However, these scans did not accurately reflect the status of disease in these patients. Scans obtained 4 months after RT were believed to assess more accurately the presence of malignancy. CONCLUSIONS: Positron emission tomography is a new modality that may be useful in defining tumor activity in clinically negative areas. Appropriately timed posttreatment PET may be useful in predicting outcome after definitive RT and in distinguishing viable tumors from normal tissue changes after RT in patients with head and neck carcinomas.