Tom R. Miller

Measurement of tumor volume by PET to evaluate prognosis in patients with advanced cervical cancer treated by radiation therapy

PURPOSE This study evaluated the usefulness of tumor volume measurement with positron emission tomography (PET) in patients with advanced cervical cancer treated by radiation therapy. METHODS AND MATERIALS Fifty-one patients underwent PET before treatment. Primary tumor volume was determined, and volume, FIGO stage, and presence of lymph nodes on the PET study were compared to progression-free survival (PFS) and overall survival (OS). RESULTS Tumor volume, lymph node disease, and stage were predictive of PFS, whereas volume and lymph node involvement predicted OS. Lymph node status did not correlate with volume. Dividing patients according to whether the tumor volume was more or less than 60 cm(3) predicted PFS and OS. Separation of patients with tumor volumes <or=60 cm(3) and no lymph node disease vs. any other combination was strongly predictive of PFS and OS. CONCLUSIONS The following conclusions were drawn regarding patients with advanced cervical cancer treated with radiation therapy: (1) Tumor volume can be accurately measured by PET; (2) Tumor volume separates patients with a good prognosis from those with a poorer prognosis; (3) A subset of patients with relatively small tumors and no lymph node involvement does remarkably well; (4) Tumor volume does not correlate with the presence of lymph node disease.

Left ventricular diastolic filling and its association with age

Thirty normal subjects, aged 22 to 80 years, were studied by radionuclide ventriculography to determine the age dependence of cardiac ventricular diastolic function and to evaluate the association of other factors with ventricular diastolic performance. A strong negative correlation was found between peak diastolic filling rate and age (r = -0.82, p less than 0.0001). Partial correlation analysis was used to factor out the strong age dependence and yielded additional significant correlations of peak filling rate with heart rate (r = 0.48, p less than 0.01) and time to peak filling rate (r = -0.48, p less than 0.01). Time to peak filling rate is also correlated with heart rate but not definitely with age. Analysis by multiple linear regression yields an equation predicting peak filling rate from age and heart rate. Thus, the rate of rapid diastolic filling declines markedly with age in normal subjects. The association of peak filling rate with age and with other factors indicates the need for careful consideration of these factors in the interpretation of scintigraphic findings in patients with heart disease.

Exercise training improves left ventricular systolic function in older men.

To determine whether endurance exercise training can improve left ventricular systolic function in older men, 10 healthy sedentary men (64 +/- 3 years old; mean +/- SD) were studied. Training consisted of endurance exercise 4 +/- 0.3 days per week for 11.8 +/- 2.5 months at a progressively increasing intensity of 60-80% of maximal O2 uptake (Vo2max) with additional brief bouts of exercise equal to 93 +/- 13% of Vo2max. Vo2max increased from 29.6 +/- 4.1 to 37.2 +/- 5.7 ml/kg/min (p less than 0.001). Percent body fat was decreased (17.8 +/- 3.6% versus 15.6 +/- 3.6%; p less than 0.001). Before training, left ventricular ejection fraction, determined by electrocardiographic-gated equilibrium blood pool imaging, increased only modestly during exercise (from 66.3 +/- 6.7% at rest to 70.6 +/- 6.9% at peak exercise). After training, the increase in ejection fraction during exercise was significantly greater (from 67 +/- 4.8% at rest to 77.6 +/- 7.5% at peak exercise) than that observed before training and was similar to that in young sedentary men (64 +/- 7% at rest versus 74 +/- 9% at peak exercise). Although the changes in systolic pressure from rest to exercise were similar, end-systolic volume decreased significantly at peak exercise after (51 +/- 12 versus 38 +/- 13 ml; p less than 0.005) but not before (46 +/- 8 versus 43 +/- 13 ml; p = NS) training with a shift in the end-systolic volume-systolic blood pressure relation to the left compatible with enhanced inotropic state.(ABSTRACT TRUNCATED AT 250 WORDS)

Three-dimensional display in nuclear medicine

Several surface and volume rendering techniques are compared using nuclear medicine data including several new methods developed by the authors specifically for scintigraphic data. The techniques examined are summed projection, thresholded projection, threshold-based surface illumination, volumetric compositing, maximum-activity projection, sun-weighted maximum-activity projection, and variable attenuation. The advantages and disadvantages of each method are discussed in relation to the goals of three-dimensional display, which are defined herein. Selected images are shown to illustrate the usefulness of the methods.

PET-GUIDED IMRT FOR CERVICAL CARCINOMA WITH POSITIVE PARA-AORTIC LYMPH NODES—A DOSE-ESCALATION TREATMENT PLANNING STUDY

PURPOSE To evaluate a treatment planning method for dose escalation to the para-aortic lymph nodes (PALNs) based on positron emission tomography (PET) with intensity-modulated radiotherapy (IMRT) for cervical cancer patients with PALN involvement. One goal of this process was not to modify the traditional treatment of the pelvic region. METHODS AND MATERIALS PET images for 4 cervical cancer patents with PALN involvement were registered with their corresponding CT scans. Positive PALNs were identified on PET images, and the surrounding critical structures were delineated on CT images. The treatment machine central axis (CAX) was placed at the level of the L4-L5 vertebral body interspace. There were two distinct treatment regions: the para-aortic bed superior to the CAX and the whole pelvis region inferior to the CAX. IMRT was used for treatment planning of PALN bed irradiation. The positive PALNs identified on PET images were defined as the gross target volume, and the para-aortic bed was defined as the clinical target volume. The radiation doses were escalated from the conventional 45 Gy to 59.4 Gy for the gross target volume and 50.4 Gy for the clinical target volume in 33 fractions. The pelvis area was treated with conventional treatment methods, AP-PA beams to 50.4 Gy in 28 fractions with a brachytherapy implant boost. The placement of the CAX allowed the two treatment regions to be abutted using the treatment machines independent jaws. RESULTS Dose escalation to positive PALNs, as identified on PET images, and the PALN bed is feasible with IMRT. Treatment plans for 4 patients revealed that escalated prescription doses could be delivered to target volumes while maintaining acceptable doses to the surrounding critical structures. Strategic placement of the treatment isocenter allows the IMRT region (PALN bed) and whole pelvis fields to be treated with a relatively uniform dose distribution in the abutment region. CONCLUSION This study indicates that PET-guided IMRT could be used in a clinical trial in an attempt to escalate doses delivered to patients with cervical cancer who have positive PALNs.

Maximum-Likelihood Reconstruction for Single-Photon Emission Computed-Tomography

A mathematical model is formulated for a gamma camera used to observe single-photon emissions from multiple view angles. The model accounts for the statistics of radioactive decays, nonuniform attenuation, and a depth-dependent point-spread function. The maximum-likelihood method of statistics is used with the model to derive an algorithm for estimating the distribution of radioactivity.

PET-guided three-dimensional treatment planning of intracavitary gynecologic implants

PURPOSE Positron emission tomography (PET) provides physiologic information that is not available from computed tomography (CT) or magnetic resonance studies. PET images may allow more accurate delineation of three-dimensional treatment planning target volumes of brachytherapy gynecologic (GYN) implants. This study evaluates the feasibility of using PET as the sole source of target, normal structure, and applicator delineation for intracavitary GYN implant treatment planning. MATERIALS AND METHODS Standard Fletcher-Suit brachytherapy tandem and colpostat applicators were used for radiation delivery. After insertion of the applicator in the operating room, the patient was taken to a PET scanner, where 555 MBq (15 mCi) 18F-fluorodeoxyglucose (18F-FDG) was administered intravenously. Forty-five minutes later, three localization tubes containing 18F-FDG were inserted into the source afterloading compartments of the tandem and colpostat. A whole-pelvis scan was performed, and the images were transferred to a commercial brachytherapy three-dimensional treatment planning system. A Foley catheter was inserted into the urinary bladder while the patient was in the operating room. The regions of radioactivity in the three applicator tube image were contoured for reconstruction of the applicator, along with the bladder, rectum, and 18F-FDG-defined target volumes. A treatment plan was generated that included dose-volume histograms and three-dimensional dose distribution displays, allowing the physician an opportunity to determine if adequate target coverage and normal-tissue sparing had been obtained. For a more conservative approach, three-dimensional dose distributions and dose-volume histograms delivered with conventional source arrangements and loading could be observed. The accuracy of applicator localization from the PET images was verified using a water phantom containing two aluminum CT-compatible tandems. The PET-defined and CT scan applicator reconstructions were compared. RESULTS Feasibility of using PET images for treatment planning of brachytherapy intracavitary GYN implants has been demonstrated. A phantom study demonstrated applicator reconstruction accuracy in the axial direction to be better than 2 mm. Reconstruction accuracy in the longitudinal direction (principally craniocaudal) was similar to the PET scanners voxel size of 4.3 mm. CONCLUSIONS Brachytherapy intracavitary GYN implant design has traditionally been based on patient tumor staging, palpation, and clinical experience. PET images have the potential to provide better spatial information about the relationship of tumor and normal structures to the applicator. This information can be used to optimize the delivery of radiation therapy treatments. Thus far, six patients have been scanned using this process.

Evaluation of Response to Neoadjuvant Therapy by Quantitative 2-Deoxy-2-[18F]Fluoro-D-Glucose with Positron Emission Tomography in Patients with Esophageal Cancer

PURPOSE This work evaluates positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) in assessing response to therapy in patients with esophageal cancer. PROCEDURES Twenty-four patients underwent FDG-PET before (pre-Rx) and after (post-Rx) chemoradiation therapy; 20 then underwent esophagectomy. The response of the primary tumors was visually assessed, and tumor volume, peak tumor standardized uptake value (SUV(peak)), average SUV (SUV(ave)), and total lesion glycolysis were determined pre-treatment and post-treatment. Patients were divided into groups according to the absence (Group A) or presence (Group B) of residual tumor after neoadjuvant therapy. RESULTS Among the quantitative PET parameters for Group A (n = 6) and Group B (n = 18), only change in tumor volume identified complete responders. Quantitative PET indices were not different in patients with or without post-Rx esophagitis. CONCLUSIONS The change in tumor volume identifies patients with complete response to neoadjuvant therapy, and quantitative evaluation of the primary tumor cannot separate post-Rx inflammation from residual tumor.

Physiologic FDG-PET three-dimensional brachytherapy treatment planning for cervical cancer ☆

PURPOSE To compare conventional two-dimensional (2D) orthogonal radiography-based brachytherapy treatment planning for cervical cancer with a three-dimensional (3D) treatment planning technique based on 18F-fluoro-deoxyglucose-positron emission tomography (FDG-PET). METHODS AND MATERIALS Eleven cervical cancer patients were included in this prospective study that evaluated one tandem and ovoid brachytherapy procedure for each patient. The patient underwent FDG-PET of the pelvis to visualize the tumor followed by a second FDG-PET scan with the FDG isotope placed inside the tandem and ovoid applicators to visualize the treatment source positions for 3D treatment planning. The tumor volumes were delineated using a binary threshold technique in which the threshold FDG-PET image intensity was 40% of the peak tumor intensity. RESULTS FDG-PET provides a reliable estimate of the cervical cancer volume and 3D spatial relationship of the tumor to the tandem and ovoid applicators. The maximal bladder and rectal doses determined from the 3D FDG-PET dose-volume histograms were found to be higher than those obtained using 2D treatment planning. The minimal dose to the tumor volume defined by FDG-PET ranged from 50 to 475 cGy for treatment plans designed to deliver 650 cGy to Point A and exhibited an inverse correlation with tumor volume. CONCLUSION Physiologic FDG-PET brachytherapy treatment planning is feasible and accurate relative to conventional 2D treatment planning. The use of FDG-PET offers a unique method for tumor visualization and identifies the limitations of conventional brachytherapy treatment planning for coverage of large tumors and estimation of the dose to normal structures. This technique has the potential for improving isodose tumor coverage for patients with cervical cancer while sparing critical structures.

Effect of exercise training on left ventricular performance in older women free of cardiopulmonary disease

Endurance exercise training increases aerobic exercise capacity (maximal oxygen consumption rate [VO2max]) and attenuates the age-related decline in left ventricular (LV) function during exercise in older men. To determine whether similar adaptations occur in older women, 10 subjects (aged 63 +/- 4 years mean +/- SE) were studied before and after 9 to 12 months of endurance exercise training. They exercised 3.85 +/- 0.06 days/week at 81 +/- 0.3% of maximal heart rate. LV function at rest and during supine exercise was assessed by radionuclide ventriculography. VO2max was increased by 21% (from 1.40 +/- 0.1 to 1.7 +/- 0.1 liter/min; p < 0.001) in response to training. Maximal heart rate and systolic blood pressure during treadmill exercise were unchanged (161 +/- 5 beats/min before vs 164 +/- 3 beats/min after; p = NS, and 208 +/- 7 mm Hg before vs 214 +/- 8 mm Hg after; p = NS, respectively) after training. LV ejection fraction at rest (70.4 +/- 2% before vs 70 +/- 1% after) and during peak exercise (78.6 +/- 2% before vs 79.3 +/- 2% after) did not change in response to training. Furthermore, the increases in ejection fraction from rest to exercise were similar before and after training (change: 8.8 +/- 1 vs 9.1 +/- 1%). Stroke volume and cardiac output at peak exercise also did not change in response to training.(ABSTRACT TRUNCATED AT 250 WORDS)