Sheila Rege

Cancer detection with whole-body PET using 2-[18F]fluoro-2-deoxy-D-glucose.

Objective This study was done to determine the feasibility and potential utility of whole-body PET using the glucose analogue 2-[18F]fluoro-2-deoxy-D-glucose (FDG) for the detection of primary malignancies and metastatic lesions. Materials and Methods This was a prospective, nonrandomized study of whole-body FDG-PET imaging carried out at a large university teaching hospital in Los Angeles, CA, U.S.A. The study group consisted of all patients referred for PET imaging (87) with a suspected diagnosis of primary or recurrent malignancy and who had eventual histological confirmation of their lesions. Results In the 87 patients, whole-body PET studies were positive (presence of focal FDG uptake relative to surrounding tissues uptake) in 61 of 70 patients (87%) with subsequent biopsy-confirmed primary or recurrent malignant lesions, including carcinomas of breast, lung, ovary, prostate, colon, urinary bladder, and gallbladder origin, as well as malignant melanoma, carcinoid, osteosarcoma, lymphoma, and spinal cord astrocytoma. The PET images revealed no focal hypermetabolism at the known site of tumor in patients with primary prostate carcinoma (two), microscopic ovarian carcinoma (two), breast carcinoma (one), low-grade carcinoid tumors (two), and one patient with recurrent microscopic osteogenic sarcoma. The PET studies detected the primary lesion in 15 of 17 patients with breast carcinoma and in 6 of 6 patients with primary lung carcinoma. Of the 17 patients with benign biopsies, 13 patients had FDG-PET studies without focal areas of uptake. Conclusion Because of the high glycolytic rate of malignant tissue, the whole-body FDG-PET technique has promise in the detection of a wide variety of both primary and metastatic malignancies. The presence of FDG uptake in benign inflammatory conditions may limit the specificity of the technique. The sensitivity for the detection of malignant lesions was 87% and the positive predictive value was 94%. The whole-body FDG-PET method is promising both in determining the nature of a localized lesion and in defining the systemic extent of malignant disease.

Positron emission tomography with fluorodeoxyglucose to evaluate tumor response and control after radiation therapy

PURPOSE Following radiation therapy, evaluation of viable tumor can often be difficult with anatomic imaging criteria (tumor size alone). In this study, the utility of biochemical imaging with the glucose analog 2-[F-18]fluoro-2-deoxy-D-glucose and positron emission tomography was investigated in patients treated with radiation therapy. METHODS AND MATERIALS Between 1990 and 1992, 19 patients were studied, including 15 patients with head and neck cancer, (4 oropharynx, 4 sinus, 3 larynx, 2 hypopharynx, 2 oral cavity [one patient], 1 nasopharynx), and 4 patients with breast cancer. Post-radiation positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose studies were done in all patients, with 9 head and neck patients receiving pre-radiation positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose scans as well. Results were correlated with other imaging techniques and pathology. RESULTS Positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose detected head and neck primary tumors and lymph node metastases in all nine pre-radiation scans, while magnetic resonance imaging failed to detect two primary tumors. Serial positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose showed a significant decrease in tumor activity after radiation therapy, compared to pre-radiation levels, (p < 0.05), except for two patients with increased uptake at the primary site. Biopsies of these two patients showed persistent/recurrent disease after radiation therapy, which was not detected by magnetic resonance imaging. Six additional head and neck patients, with suspicious examination and inconclusive magnetic resonance imaging, were imaged with positron emission tomography after radiation therapy only. Five patients had increased positron emission tomography activity, with corresponding biopsies positive in four patients, and negative in one patient with clinically worsening symptoms. The remaining sixth patient had minimal and stable positron emission tomography uptake, and is improving clinically. Four patients had mammogram findings suspicious for recurrence after conservation treatment for breast cancer. Positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose showed no focal activity in the breast in two patients, and increased activity in the area suspicious for recurrence in the other two patients. Biopsies correlated with positron emission tomography results. CONCLUSION Changes and presence of positron emission tomography with 2-[F-18]fluoro-2-deoxy-D-glucose activity correlated with pathologic findings in head and neck and breast cancer patients in this series. In patients with elevated or rising positron emission tomography activity after radiation therapy, persistent or recurrent disease was found in 89% of patients, (8/9). Magnetic resonance imaging did not detect the head and neck recurrences, and mammography was suspicious in patients with both benign and malignant breast changes after radiation therapy. In addition, our data indicate that in head and neck patients with pre-radiation positron emission tomography scans, a significant decrease in activity should occur after radiation therapy, if local control is to be expected.

Accuracy and clinical impact of mediastinal lymph node staging with FDG-PET imaging in potentially resectable lung cancer.

To determine the sensitivity, specificity, and accuracy of staging mediastinal nodal disease in potentially resectable lung cancer using fluorodeoxyglucose-positron emission tomography (FDG-PET), computed tomography (CT), or both and compare these results to surgical staging. We also assessed whether PET scanning results changed clinical management. From 1992 to 1997, 50 patients underwent CT, and PET scanning before or close to the time of surgical staging. Sensitivity, specificity, accuracy, and predictive values were then calculated based on pathology results. A retrospective review of the records was performed to determine how PET results affected clinical treatment decisions. Forty-seven of 50 patients had non-small-cell lung cancer. The prevalence of pathologically confirmed mediastinal and hilar involvement was 38%. The sensitivity, specificity, and accuracy of mediastinal disease staging were as follows: CT alone = 73%, 77%, 76%; PET alone = 73%, 94%, 87%; PET + CT = 82%, 96%, 91%, respectively. PET was more specific and accurate than CT (p = 0.025). The results of PET changed management decisions in 12 of 50 cases (24%). Using FDG-PET in conjunction with CT scanning provides the most accurate staging of mediastinal disease in lung cancer by contributing complementary information. Furthermore, PET can affect clinical decision-making and allow some patients considered unresectable a chance for resection.

Quantification of glucose utilization in liver metastases: parametric imaging of FDG uptake with PET.

Positron emission tomography (PET) fluorodeoxyglucose (FDG) studies are useful for identifying foci of increased FDG uptake in liver metastases, because of the high glycolytic rate of malignancies, as well as for monitoring changes in tumor glucose metabolism during treatment. We performed 15 kinetic PET FDG studies in four patients with metastatic liver disease. We produced parametric images of glucose metabolism in terms of the rate constant K (ml/min/g) for net phosphorylation of FDG. Tumor K values, estimated with nonlinear regression, correlated well with K values estimated with Patlak graphical analysis (r = 0.96), validating the assumption of low k4* values in liver metastases and supporting the use of pixel by pixel Patlak plot analysis of the data to generate parametric images. In normal liver, high levels of glucose-6-phosphatase produce much higher values of k4* than in liver metastases. Uncorrected Patlak graphical analysis underestimates K in normal liver, but this further increases the contrast between tumor and liver and facilitates both tumor detection and quantification. The technique is computationally feasible and is well suited for serial evaluations of tumor metabolism during treatment.

The role of positron emission tomography in oncology and other whole-body applications

Imaging and quantifying biochemical and physiological processes with PET clearly has major potential significance for all organ systems and many disease states. Although the full utility and potential of emerging new applications of PET in organs other than the heart and brain must be demonstrated in basic and clinical research studies, the rapidly accumulating aggregate experience in oncology in particular, and in other organ systems and disease states as well, indicates that PET is now truly becoming a modality of both clinical and investigative use for the body as a whole as well as for specific organ systems. Whole-body PET FDG imaging (Fig 9) illustrates the potential of biochemical imaging to map the distribution of cancer throughout the body. With the growing list of radiopharmaceutical and quantitative techniques applicable to cancer studies with PET, this field will continue to realize significant growth.

Positron emission tomography: an independent indicator of radiocurability in head and neck carcinomas.

Positron emission tomography (PET) is a biochemical-imaging tool that uses the uptake of the glucose analog 2-deoxy-2-[F-18] fluoro-D-glucose (FDG) to detect head and neck tumor proliferation. The aim of this study is to determine if quantitation of either primary tumor metabolic activity or tumor response using PET scans could predict local control and overall survival in patients with head and neck cancer undergoing primary radiotherapy. Twelve patients with squamous cell carcinomas of the head and neck underwent PET scans before and 6 weeks after completion of radiation therapy. Tumor metabolic activity was quantitated using the metabolic ratio method. Mean follow-up was 40 months (range: 18-55 months). In our series, tumors with metabolic rates greater than that of the cerebellum are associated with significantly better local control (p < 0.05) and survival. Posttreatment PET imaging was falsely positive in one patient with clinical signs of severe inflammation. Tumors with greater than 50% decrease in metabolic activity with irradiation had improved local control. Clinically, nine patients had excellent response to irradiation. These results suggest that pretreatment PET findings may have prognostic implications in determining which patients will achieve long-term local control with primary radiation therapy. This may help identify those at increased risk of recurrence that may benefit from more aggressive altered fractionation schemes or combined modality therapy.

The use and advantages of a multichannel vaginal cylinder in high-dose-rate brachytherapy

PURPOSE This paper describes California Endocurietherapys (CET) high-dose-rate (HDR) multichannel cylinder, the rationale for its design, procedure for its insertion, and the dosimetry involved in its use. A study was done that compared the doses achieved using the CET multichannel cylinder to the same cylinder if it only had a central channel. METHODS AND MATERIALS The CET multichannel vaginal cylinder was inexpensively constructed, using parts from various suppliers. After insertion in the patient, the cylinder is affixed to a base plate to prevent displacement. Two sets of orthogonal films (without and with rectal barium) are taken in preparation for digitization of the catheters, bladder, rectal, and pelvic sidewall points. Using HDR brachytherapy planning software, the dose distribution is adjusted to achieve the prescribed dose (5 Gy HDR) 5 mm lateral to the cylinder surface, 5 mm lateral at the proximal parametrial tissue, and 4 mm superior to the vaginal apex. Doses to the bladder and rectum are limited to approximately 85% and 75%, respectively, of the prescribed dose. The plan is optimized on geometric parameters. For dose comparison to treatment using a central channel cylinder, the lateral channels are de-activated, leaving only the central channel activated. Dose points are placed 5 mm laterally and superiorly from the cylinder surface, and the plan is optimized to deliver a uniform dose to the defined dose points. The doses and treatment volumes are statistically compared. RESULTS The CET multichannel cylinder allows much better dose control than the central channel cylinder. The multichannel cylinder achieves lower bladder and rectal doses by 14% and 15%, respectively, when compared to the central channel cylinder. By increasing the dwell times of certain dwell positions, the prescription dose is achieved in the vaginal apex and proximal parametrial tissues and along the length of the cylinder. CONCLUSION The multichannel cylinder enables more flexibility in isodose shaping and dose control to various points and structures when compared to the conventional central channel cylinder.

Accuracy and clinical impact of mediastinal lymph node staging with FDG-PET imaging in potentially resectable lung cancer

To determine the sensitivity, specificity, and accuracy of staging mediastinal nodal disease in potentially resectable lung cancer using fluorodeoxyglucose-positron emission tomography (FDG-PET), computed tomography (CT), or both and compare these results to surgical staging. We also assessed whether PET scanning results changed clinical management. From 1992 to 1997, 50 patients underwent CT, and PET scanning before or close to the time of surgical staging. Sensitivity, specificity, accuracy, and predictive values were then calculated based on pathology results. A retrospective review of the records was performed to determine how PET results affected clinical treatment decisions. Forty-seven of 50 patients had non-small-cell lung cancer. The prevalence of pathologically confirmed mediastinal and hilar involvement was 38%. The sensitivity, specificity, and accuracy of mediastinal disease staging were as follows: CT alone = 73%, 77%, 76%; PET alone = 73%, 94%, 87%; PET + CT = 82%, 96%, 91%, respectively. PET was more specific and accurate than CT (p = 0.025). The results of PET changed management decisions in 12 of 50 cases (24%). Using FDG-PET in conjunction with CT scanning provides the most accurate staging of mediastinal disease in lung cancer by contributing complementary information. Furthermore, PET can affect clinical decision-making and allow some patients considered unresectable a chance for resection.

Evaluation of cancer detection with whole-body positron emission tomography (PET) and 2-[F-18]fluoro-2-deoxy-D-glucose

Until recently, positron emission tomography (PET) has been acquired and displayed in a standard transaxial image format. The development of whole body PET has allowed biochemical and physiologic imaging of the entire body, expanding the limited axial field of view of the conventional PET scanner. In this study, the application of whole body PET studies with 2-[F-18]fluoro-2-deoxy-D-glucose (FDG) for tumor imaging was evaluated. Whole body PET studies were positive (presence of focal FDG uptake relative to surrounding tissue activity) in 61 of 70 patients (87%) with biopsy confirmed malignant tumors. PET images failed to reveal focal hypermetabolism in 9 of the 70 patients. Of the 17 patients with benign biopsies lesions, 13 patients had whole body PET studies without focal areas of FDG uptake. Because of the high glycolytic rate of malignant tissue, the whole body PET FDG technique has promise in the detection of a wide variety of both primary and metastatic malignancies. The presence of FDG uptake in benign inflammatory conditions may limit the specificity of the technique. The true positive rates for the characterization of known lesions was 87% in this series, and the PET FDG method is promising both in determining both the nature of a localized lesion, and in defining the systemic extent of malignant disease.