Actual Tumor Volume Research Articles

P-0099 - Computed Tomography Scan and Image Reconstruction Models Affects the Target Volume of Liver Cancer Radiotherapy

Introduction: Evaluation the tumor volume for liver cancer radiotherapy is usually performed by computed tomography scan. However, respiratory motion would cause variations of the position, volume and shape of the tumor on the CT image and result in deviation of target volume. This study will evaluate the influences of different CT scan and image reconstruction models towards target volume for liver cancer radiotherapy. Methods: This study employed a home-made movable platform and liver tumor phantoms to simulate respiratory motion of human body. The movable platform was set up with different amplitudes and periods to explore various CT scan and reconstruction models of 4D CT-MIP, 4D CT-AIP, helical CT and slow CT. The differences among actual tumor volume and the target volumes produced by various CT scan and image reconstruction models were analyzed with a reconstructed 3D image of liver tumor after the scanning. Results: The image reconstruction showed that the 4D CT-MIP provided clear tumor area and detected the tumor boundaries specifically. The area of tumor target was accurately delineated when determining the gross tumor volume in treatment planning system. The differences 4D CT-AIP and 4D CT-MIP for R-L, A-P and S-I directions were less than 0.5cm. When compared with 4D CT-MIP and slow CT were 2.8 cm and 1.6 cm, respectively. The reconstruction images of bigger tumors had greater deviations than the smaller ones. No matter what the volume was, the reconstructed images from 4D CT-MIP were the closest to the actual target volume. Conclusion: 4D CT-MIP could completely define the motion ranges of the tumor during respiration and allow the tumor to receive complete radiation doses and promote the effectiveness of liver cancer radiotherapy.

Three‐dimensional tumor volume and serum alpha‐fetoprotein are predictors of hepatocellular carcinoma recurrence after liver transplantation: refined selection criteria

Total tumor volume (TTV), as a better predictor of hepatocellular carcinoma (HCC) recurrence after liver transplant, has been explored by our center. Some tumors are not typically spherical but rather ellipsoid or spheroid, and calculating their TTV based on one dimension only may overestimate their volume and exclude them from candidacy for transplantation. Our aim was to study the actual tumor volume (ATV) calculated using the ellipsoid formula and assess its impact on recurrence. HCC patients transplanted between 1990 and 2010 at University of Alberta Hospital were analyzed. Tumor volumes were calculated using both formulas: [(4/3) πr(3)] (r = max. radius) and [(4/3) πabc] (a, b, c = the 3 radiuses). A total of 115 patients were included with a mean follow-up of 4.99 ± 4.23 yr. Five-yr recurrence-free survival was 79.8%. Univariate analysis for predictors of recurrence included: maximum tumor diameter, ATV, TTV, and alpha-fetoprotein (AFP) ≥ 400 ng/mL. Multivariate analysis showed that ATV and AFP ≥ 400 ng/mL were the only predictors of recurrence. Combining both variables provides better predication of recurrence with accuracy that exceeds 80%. Three-dimensional calculation of tumor volume is of critical importance for the group of patients with ellipsoid tumors where volumes are overestimated with the spherical formula and could lead to inappropriate exclusion from transplant.

Abstract P4-01-09: 18F-FLT-PET/CT for the prediction of response to ANG-1005 therapy in patients with brain metastases from breast cancer

Abstract Background: ANG1005 (formerly called GRN1005) is a peptide-drug conjugate being developed for targeted treatment of brain metastases. It consists of 3 molecules of paclitaxel covalently linked to Angiopep-2 designed to cross the blood brain barrier (BBB) via the low density lipoprotein (LDL) receptor-related protein-1 (LRP1)-mediated trancytosis. This drug was evaluated in a multi-center, open-label single-arm study (GRABMB study). An interim analysis determined that the agent met the futility endpoint based on MRI assessment (SABC 2012). However, centrally confirmed responses were achieved in the study, and a biomarker substudy enrolling patients (pts) to evaluate the utility of FLT-PET in assessing response to treatment with ANG1005 suggested sufficient activity of the agent to allow continuation of the study. 18F-FLT (3’-Fluoro-3’ deoxythymidine)-PET imaging is a novel imaging modality which provides a tool for measuring in vivo tumor cell proliferation. FLT is an analog of thymidine; cellular retention of FLT reflects DNA synthesis. Methods: Adult pts with measurable BMBC were eligible with or without history of prior WBRT. We compared 18F-FLT-PET/CT with MRI-gadolinium contrast images for brain metastases detection and for assessment of whether treatment with ANG1005 was associated with significant change in intracranial tumor uptake of 18F-FLT. ANG1005 therapy was administered intravenously at 550 mg/m2 q 21d until progression of intra-cranial disease or unacceptable toxicity. All pts underwent 18F-FLT PET/CT imaging before and after 1 cycle of therapy with ANG1005. Pts were scanned dynamically over 30 min followed by a static whole body PET image at 1 hour post-injection. We calculated the% of change before and after therapy, with change > 20% considered significant. Results: 5/10 planned pts have been accrued to the substudy to date, and 12 metastatic brain lesions have been analyzed. The maximum standard uptake value (SUVmax) ranged from 0.8 to 4.0, mean 1.8 for baseline scans. Tumor to normal brain background ratios ranged from 3.2 to 22.3, mean 9.4. 7/12 lesions showed >20% change between pre and post therapy. The average% change was (-) 42.39% ± 12.77, range: 29.2 to 66.8% (using SUVmax), and (-) 38.7% ± 14.3, range: 20.12 to 57.10% (using tumor to normal ratios). Based on brain MRI evaluation per RECIST 1.1 criteria, 1 pt had intra-cranial partial response (PR) and 3 patients had stable disease (SD). These pts remained on therapy for an average of 7 cycles, range: 5 to 9 cycles. 1 pt withdrew consent after 2 cycles of therapy and opted to receive whole brain radiation therapy. 5/42 pts achieved a confirmed investigator-assessed PR by MRI at 550 mg/m2, and 4/13 pts achieved a PR at 650 mg/m2, a dose not progressed due to toxicity. Conclusion: This pilot study using 18F-FLT-PET imaging of brain metastases suggests that it is a promising tool for detection and measurement of CNS disease. Given that contrast-enhanced MRI detection of brain metastases represent gadolinium leakage through the BBB rather than actual tumor volume measurements, better approaches are needed to assess efficacy of therapies. Accrual to this study is ongoing. Updated results with ANG1005 will be presented during the meeting. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-01-09.

Tumor volume successively reflects the state of disease progression in endometrial cancer

ObjectiveThis study aimed to clarify the clinical significance of tumor volume in endometrial cancer. MethodsA total of 667 patients with endometrial cancer who underwent preoperative MRI and surgical treatment including lymphadenectomy were enrolled. As the surrogate marker of actual tumor volume, the volume index was defined as the product of the maximum longitudinal diameter along the uterine axis, the maximum intersecting anteroposterior diameter of the sagittal section image, and the maximum horizontal diameter of the horizontal section image from the MRI data. The volume index was divided into five categories: Group 1 (<8), Group 2 (8 to <27), Group 3 (27 to <64), Group 4 (64 to <125), and Group 5 (125 or more). The relationships between various clinicopathologic factors and volume index were investigated, and Cox regression analysis was conducted to assess the significance of volume index with respect to prognosis. ResultsHigh-risk clinicopathologic findings increased with tumor volume. The lymph node metastasis rate was 3% in Group 1, 9% in Group 2, 17% in Group 3, 25% in Group 4, and 53% in Group 5. Cox regression analysis showed that the volume index (≥36) was a prognostic factor (hazard ratio: 2.0, 95% confidence interval: 1.3–3.1) independent of older age (≥58years), high-risk histological grade/subtype, deep myoinvasion, lymph node metastasis, and type of surgery. ConclusionTumor volume successively reflects the state of disease progression in endometrial cancer. The volume index can give information on both the staged prognosis and surgical management.

Artifact-reduced simultaneous MRI of multiple rats with liver cancer using PROPELLER

To explore simultaneous magnetic resonance imaging (MRI) for multiple hepatoma-bearing rats in a single session suppressing motion- and flow-related artifacts to conduct preclinical cancer research efficiently. Our institutional Animal Experimental Committee approved this study. We acquired PROPELLER (periodically rotated overlapping parallel lines with enhanced reconstruction) T2 - and diffusion-weighted images of the liver in one healthy and 11 N1-S1 hepatoma-bearing rats in three sessions using a 3-T clinical scanner and dedicated multiarray coil. We compared tumor volumes on MR images and those on specimens, evaluated apparent diffusion coefficients (ADC) of the tumor, and compared them to previously reported values. Each MRI session took 39-50 minutes from anesthesia induction to the end of scans for four rats (10-13 minutes per rat). PROPELLER provided artifact-reduced T2 - and diffusion-weighted images of the rat livers. Tumor volumes on MR images ranged from 0.04-1.81 cm(3) and were highly correlated with those on specimens. The ADC was 1.57 ± 0.37 × 10(-3) mm(2) /s (average ± SD), comparable to previously reported values. PROPELLER allowed simultaneous acquisition of artifact-reduced T2 - and diffusion-weighted images of multiple hepatoma-bearing rats. This technique can promote high-throughput preclinical MR research for liver cancer.

Evaluation of Tumor Position and PTV Margins Using Image Guidance and Respiratory Gating

To evaluate the margins currently used to generate the planning target volume for lung tumors and to determine whether image-guided patient setup or respiratory gating is more effective in reducing uncertainties in tumor position. Lung tumors in 7 patients were contoured on serial four-dimensional computed tomography (4DCT) data sets (4-8 4DCTs/patient; 50 total) obtained throughout the course of treatment. Simulations were performed to determine the tumor position when the patient was aligned using skin marks, image-guided setup based on vertebral bodies, fiducials implanted near the tumor, and the actual tumor volume under various scenarios of respiratory gating. Because of the presence of setup uncertainties, the reduction in overall margin needed to completely encompass the tumor was observed to be larger for imaged-guided patient setup than for a simple respiratory-gated treatment. Without respiratory gating and image-guided patient setup, margins ranged from 0.9 cm to 3.1 cm to completely encompass the tumor. These were reduced to 0.7-1.7 cm when image-guided patient setup was simulated and further reduced with respiratory gating. Our results indicate that if respiratory motion management is used, it should be used in conjunction with image-guided patient setup in order to reduce the overall treatment margin effectively.

1P1-C07 頭頸部リンパ節腫瘍における放射線治療シミュレーション

The importance of accurate prediction of the radiotherapeutic effect has increased recently with developing the irradiation techniques. The authors have proposed a novel computational method to simulate changes in tumor volume during the treatment. In this work, the method was applied to six clinical cases of metastatic cervical lymph nodes to examine the feasibility of clinical application of this method. The volume change in tumor shrinkage during treatment was formulated mathematically using analogical equations of an elastic deformation in solid mechanics. The values of simulation parameters were determined for each case so that calculated tumor volume change could be obeyed actual tumor volume change through the treatment. The average difference between the calculated and measured volumes for the six cases was 9.9%. The simulation method was able to represent various patterns of decreases in tumor volume in the cases of metastatic cervical lymph nodes.

Computer Simulation of Radiotherapy for Malignant Tumor - A Mechanical Analogy Method -

A new simulation method was developed that considered a tumor as a solid body and therapeutic response as deformation of the tumor using mechanical analogy. As radiation exposure to the tumor was related to the external force to the solid body, the geometrical change of the tumor could be estimated from fundamental equations in solid mechanics. A change in tumor volume was calculated using finite element (FE) method. The FE models were constructed from CT images of patients before the radiotherapy. The initial radiotherapeutic parameters of tumor radioresistance and repopulation rate were determined based on a linear-quadratic model and then revised by the comparison with actual tumor volume change. Three patients with uterine cervix carcinoma were applied in this method. Simulation results well showed tendencies of tumor volume changes with radiotherapy. In addition, this method could provide the appropriate value of radiotherapeutic parameters for individual case. In conclusion, our approach could calculate three-dimensional tumor deformation during the course of radiotherapy and will provide useful information for more effective treatment.

Fully automated segmentation of oncological PET volumes using a combined multiscale and statistical model

The widespread application of positron emission tomography (PET) in clinical oncology has driven this imaging technology into a number of new research and clinical arenas. Increasing numbers of patient scans have led to an urgent need for efficient data handling and the development of new image analysis techniques to aid clinicians in the diagnosis of disease and planning of treatment. Automatic quantitative assessment of metabolic PET data is attractive and will certainly revolutionize the practice of functional imaging since it can lower variability across institutions and may enhance the consistency of image interpretation independent of reader experience. In this paper, a novel automated system for the segmentation of oncological PET data aiming at providing an accurate quantitative analysis tool is proposed. The initial step involves expectation maximization (EM)-based mixture modeling using a k-means clustering procedure, which varies voxel order for initialization. A multiscale Markov model is then used to refine this segmentation by modeling spatial correlations between neighboring image voxels. An experimental study using an anthropomorphic thorax phantom was conducted for quantitative evaluation of the performance of the proposed segmentation algorithm. The comparison of actual tumor volumes to the volumes calculated using different segmentation methodologies including standard k-means, spatial domain Markov Random Field Model (MRFM), and the new multiscale MRFM proposed in this paper showed that the latter dramatically reduces the relative error to less than 8% for small lesions (7 mm radii) and less than 3.5% for larger lesions (9 mm radii). The analysis of the resulting segmentations of clinical oncologic PET data seems to confirm that this methodology shows promise and can successfully segment patient lesions. For problematic images, this technique enables the identification of tumors situated very close to nearby high normal physiologic uptake. The use of this technique to estimate tumor volumes for assessment of response to therapy and to delineate treatment volumes for the purpose of combined PET/CT-based radiation therapy treatment planning is also discussed.

Potential Time Benefit in the Assessment of Recurrent Rat Rhabdomyosarcoma Using Positron Emission Tomography (PET) with 18Fluorodeoxyglucose Depends on Therapy-Specific Growth Delay

To correlate the potential time benefit of (18)F-fluorodeoxyglucose positron emission tomography ((18)FDG-PET) in terms of early detection of recurrences of subcutaneously growing R1H tumors with therapy-specific parameters of recurrent tumor. Twelve, eleven, and seven recurrences were followed after fractionated radiotherapy, surgery, and chemotherapy for 6 months, respectively, and (18)FDG-PET was performed weekly using a conventional full-ring whole-body PET scanner. By comparing PET results and actual tumor volume, the time benefit of (18)FDG-PET in detection of recurrent tumors of 0.1, 0.2, and 0.5 cm(3) was determined for the different treatment strategies. A significant time benefit of (18)FDG-PET of 26.9 days and 67 days was solely determined for recurrences after radiotherapy of 0.2 cm(3) and 0.5 cm(3), respectively. The potential time benefit showed a strong correlation with growth delay, which was increased after radiotherapy due to a pronounced tumor-bed effect. The potential time benefit of (18)FDG-PET is strongly determined by the growth kinetics of the recurrence. A tumor-bed effect, which is a phenomenon solely seen after radiotherapy, favors early detection by (18)FDG-PET. The experimental data, clinical experience and theoretical consideration all indicate a noticeable benefit of (18)FDG-PET especially after radiotherapeutic treatment.

Technical aspects and evaluation methodology for the application of two automated brain MRI tumor segmentation methods in radiation therapy planning

The purpose of this study was to design the steps necessary to create a tumor volume outline from the results of two automated multispectral magnetic resonance imaging segmentation methods and integrate these contours into radiation therapy treatment planning. Algorithms were developed to create a closed, smooth contour that encompassed the tumor pixels resulting from two automated segmentation methods: k-nearest neighbors and knowledge guided. These included an automatic three-dimensional (3D) expansion of the results to compensate for their undersegmentation and match the extended contouring technique used in practice by radiation oncologists. Each resulting radiation treatment plan generated from the automated segmentation and from the outlining by two radiation oncologists for 11 brain tumor patients was compared against the volume and treatment plan from an expert radiation oncologist who served as the control. As part of this analysis, a quantitative and qualitative evaluation mechanism was developed to aid in this comparison. It was found that the expert physician reference volume was irradiated within the same level of conformity when using the plans generated from the contours of the segmentation methods. In addition, any uncertainty in the identification of the actual gross tumor volume by the segmentation methods, as identified by previous research into this area, had small effects when used to generate 3D radiation therapy treatment planning due to the averaging process in the generation of margins used in defining a planning target volume.

Use of effective core volume obtained from transrectal biopsies for predicting target tumor volume

Objectives To evaluate, in a retrospective review, whether the concept of effective core volume is useful for predicting the volume of a tumor focus identified by transrectal needle biopsy of the prostate gland. Methods The tumor volume range was estimated according to the concept of an effective core volume using the numbers of total and positive biopsy cores from the peripheral zone and peripheral zone prostate volume in 32 patients with prostate cancer with one to three cancer-positive cores who only underwent radical prostatectomy after transrectal prostate biopsy. The estimated tumor volume was compared with the actual tumor volume as determined by pathologic examination of whole mount sections of the prostatectomy specimens. Results In the 32 patients, the actual tumor volume was within the range determined by the effective core volume concept in 24 patients (75.0%), although 4 (12.5%) had a smaller focus and 4 (12.5%) a larger focus than estimated. Overall accuracy improved up to 84.4% (27 of 32) if 5% safety margins were applied to the range determined by the effective core volume concept. In particular, the accuracy was 87.5% (14 of 16) in patients with one positive core after transrectal systemic biopsy. Conclusions The effective core volume can be used to predict the volume of prostate cancer with acceptable accuracy. It can provide an assumed maximal tumor volume and valuable information for clinical decision making of the treatment strategy, particularly in cases with one positive core.

Correlation of tumor volume and surface area with lymph node status in patients with multifocal/multicentric breast carcinoma.

Multicentric breast carcinomas have a higher frequency of axillary lymph node metastasis than unifocal tumors of similar stage. It remains unclear whether this merely reflects larger tumor volumes or a different biologic behavior. The authors have shown previously that when aggregate tumor diameter are used for staging, unifocal and multifocal tumors have a similar frequency of axillary lymph node metastasis. However, summing diameter overestimates actual tumor volume because volume is proportional to the third power of the diameter. Therefore, the aim of the current study was to reanalyze the relation between size and axillary lymph node status by correcting for tumor volumes and surface areas. Volumes and surface areas of 122 breast tumor specimens with multiple macroscopic nodules (two foci: n = 95; three foci: n = 22; three foci: n = 5) were calculated by approximating the shape of each tumor nodule to an ellipsoid (for volume) or to a prolate spheroid (for area). For comparison, the authors used an internal control series, comprised of 469 macroscopic unifocal tumors. For all patients, multiple assessments of largest tumor size and combined size of all foci were correlated with the status of axillary lymph nodes. The associations between lymph node status, tumor volume or area, and multifocality were modeled using univariate and multivariate logistic regression. When either the largest or the aggregate tumor volume was used as a size estimate, tumor specimens with multiple nodules had a higher frequency of lymph node involvement compared with unifocal tumors of a similar volume or area. The odds ratio (OR) for having positive lymph nodes was 2.34 for aggregate volume measurement (P < 0.001). Surface area estimates yielded similar results (OR = 2.2, P < 0.001). Breast tumors with multiple macroscopic nodules had a different biology, with a propensity to dissemination at smaller tumor volumes (i.e., there was another factor besides volume alone that accounted for the differences in behavior).

Can errors in reconstructing pre-chemotherapy target volumes contribute to the inferiority of sequential chemoradiation in stage III non-small cell lung cancer (NSCLC)?

Concurrent chemo-radiotherapy (CT-RT) has been shown to be superior to sequential CT-RT for stage III non-small cell lung cancer (NSCLC). Pre-chemotherapy gross tumor volumes (GTV) are commonly contoured for sequential CT-RT and, as significant inter-clinician variability exists in defining GTV's for lung cancer, we postulated that the poorer local control observed with sequential CT-RT may partly be due to the larger errors in defining GTV after chemotherapy-induced tumor regression. Pre-and post-chemotherapy CT scans for RT planning (RTP) were performed in ten patients who received induction chemotherapy for NSCLC. Image registration of pre- and post-chemotherapy RTP scans was performed for all patients. GTV's were first contoured in the conventional manner by two clinicians, i.e. by visual reconstruction from hard copies of the pre-chemotherapy diagnostic CT scans (‘GTV-visual’). A ‘GTV-match’ was then contoured after image-registration, and the ‘gold standard’ volume was considered to be the overlap of the ‘GTV-match’ generated by both clinicians. The ‘GTV-match’ was on average 31–40% larger than ‘GTV-visual’. The mean percentage of the ‘gold standard’, which was not covered by the ‘GTV-visual’ was similar for both clinicians, i.e. 26.3±12.5 and 28.0±15.0%. The inter-clinician agreement in contouring improved after image registration. These data suggest that conventional visual contouring of pre-chemotherapy GTV's may fail to treat the actual pre-chemotherapy tumor volume, and thus confound studies evaluating optimal sequencing of chemo-radiotherapy in NSCLC.

DOES INCREASED NEEDLE BIOPSY SAMPLING OF THE PROSTATE DETECT A HIGHER NUMBER OF POTENTIALLY INSIGNIFICANT TUMORS?

Several studies have documented that increased biopsy sampling, that is 6 versus 12 biopsy cores, can detect more prostate cancer. It is unknown whether increased sampling of the prostate will detect a higher number of potentially insignificant tumors. We searched the surgical pathology files at The Johns Hopkins Hospital for patients in whom prostate needle biopsy was performed by a single urologist between April 1993 and April 2000, and subsequently underwent radical prostatectomy. Patients who underwent radical prostatectomy and had 8 core biopsies or less between March 1994 and August 1999 were also studied. Clinically significant tumors were defined as those with volume greater than 0.5 cc, Gleason score 7 or greater or nonorgan confined disease. A total of 297 patients with a mean age of 60 years (range 36 to 75) were evaluated. Group 1 consisted of 107 men with 8 core biopsies or less, including 51 with 6, and group 2 comprised 190 men with 9 cores or greater, including 145 with 12. The 2 groups were equal in regard to prostate specific antigen, age, digital rectal examination and transrectal ultrasound gland volume at biopsy. The only difference between the groups was a higher number of cores with cancer in group 2 (mean 2.8 versus 2.1, p = 0.0006). Of the patients who underwent radical prostatectomy 59.6% had Gleason score 6 or less, 26.3% 3+4, 6.7% 4+3 and 7.4% 8 to 9. There were 12.4% of patients with positive margins, 36.4% extraprostatic extension, and 5.4% seminal vesicle invasion and/or lymph node metastasis. Tumor volumes averaged 1.1 cc (range 0.01 to 10.7) and 60.9% of tumors were greater than 0.5 cc. Clinically significant tumors were seen in 77.4% of patients in group 1 and 74.6% in group 2. There was no significant difference in Gleason score, margin status, tumor volume, seminal vesicle invasion, or lymph node metastasis between groups 1 and 2, or in a subset analysis of men with 6 versus 12 core biopsies. However, patients in whom cancer was diagnosed with 9 core biopsies or greater were more likely to have organ confined disease (p = 0.02). Although increased sampling of the prostate does not increase the detection of potentially insignificant tumors, it does appear to detect earlier stage cancer.

Kinetic Analysis of Malignant Fibrous Histiocytoma Cells Treated with Anticancer Agents In Vivo.

To clarify the in vivo effects and the changes in kinetic parameters of soft tissue sarcoma caused by anticancer agents, we performed double-labeling using bromo- (BrdU) and iododeoxyuridine (IUdR). A malignant fibrous histiocytoma cell line was transplanted into nude mice, and treated with 3 anticancer agents: cisplatin, doxorubicin and vincristine. The following parameters were determined: BrdU labeling index (LI), duration of S-phase (Ts), total cell cycle time (Tc), Ki-67 labeling index (KLI), PCNA labeling index (PCNA-LI), and actual tumor volume doubling time (Tv). In addition, the apoptotic cell ratio (apoptotic index; Al) was calculated in the serial specimens using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL).Vincristine inhibited the tumor growth the most effectively (Tv: -5.8 days). Doxorubicin suppressed the tumor growth better (Tv: 12.7 days) than cisplatin (Tv: 9.1 days). Tc values showed significant differences among the drug groups (ANOVA analysis; p 0.7, p<0.05) on Day 1. Al peaked on Day 10 and decreased afterward in every drug group.Anticancer agents effectively suppress tumor growth not only by necrosis and apoptosis, but also by prolonging Tc. Tc values are possibly useful for planning chemotherapy for sarcoma patients.

Tumor size evaluated by pelvic examination compared with 3-D MR quantitative analysis in the prediction of outcome for cervical cancer

Tumor size estimated by pelvic examination (PE) is an important prognostic factor in cervical cancer treated with radiation therapy (RT). Recent histologic correlation studies also showed that magnetic resonance (MR) imaging provides highly accurate measurements of the actual tumor volume. The purpose of this study was to: (a) compare the accuracy of PE and MR in predicting outcome, and (b) correlate tumor measurements by PE versus MR. Tumor measurements were performed prospectively in 43 patients with advanced cervical cancer. MR and PE were performed at the same time intervals: (a) at the start of RT, (b) after 20-24 Gy/2-2.5 weeks, (c) after 40-50 Gy/4-5 weeks, and (d) at follow-up (1-2 months after RT completion). PE measured tumor diameters in anteroposterior, lateral, and craniocaudal direction, and PE-derived tumor size was computed as maximum diameter, average diameter, and ellipsoid volume. MR-derived tumor size was calculated by summation of the tumor areas in each section and multiplication by the section thickness. Tumor regression during RT was calculated for each method as percentage of initial volume. The measurements were correlated with local failure and disease-free survival. Median follow-up was 29 months (range: 9-56 months). Prediction of local control: Overall, tumor regression rate (rapid versus slow) was more precise than the initial tumor size in the prediction of outcome. MR provided a more accurate and earlier prediction of local control (at 2-2.5 weeks, and at 4-5 weeks of RT) than PE (only at follow-up). Based on the initial tumor size, MR was also better than PE in predicting disease-free survival and local control, particularly in large (> or = 100 cm3) tumors. Size correlation: Tumor size (maximum diameter, average diameter, volume) by PE and MR did not correlate well (r = 0.51, 0.61, and 0.58, respectively). When using MR measurements as a reference, PE tended to overestimate intermediate-size (40-99 cm3) tumors. This preliminary study suggests that increased precision of tumor volume measurement leads to more accurate and earlier prediction of outcome in cervical cancer. MR tumor volumetry may be useful as an adjunct to PE in selected cases, and holds the potential to impact therapeutic decision-making.

Local staging of prostate cancer with endorectal MR imaging: correlation with histopathology.

To evaluate the accuracy of MR imaging of the prostate with an endorectal surface coil in determining presence, localization, volume, and local stage of prostate carcinoma. MR images of 34 patients with biopsy-proven cancer were correlated retrospectively with the histologic mappings of radical prostatectomy specimens. The volume and number of tumor lesions of MR images were calculated and compared with the surgical specimens used as the gold standard. Tumor stage based on MR imaging was compared with the pathologic stage according to the TNM classification. Predictive values were calculated separately for all lesions and for the lesions correctly localized with MR imaging. MR imaging correctly depicted the location of 67% of the tumors. Twenty percent of the lesions depicted by MR imaging appeared to be false-positive errors. The tumors that were missed were located centrally and ventrally in the prostate. Tumor volume as shown by MR imaging was within a 25% range of the actual tumor volume in 10 cases, overestimated in 16 cases, and underestimated in eight cases. Histopathology showed capsular penetration in 12 of 34 patients (35%) and in 14 of 52 lesions (27%). Sensitivity, specificity, and positive predictive values were 43%, 84%, and 55%, respectively. Histologically, capsular penetration extended less than 1 mm into the periprostatic adipose tissue in seven patients. Sensitivity for capsular penetration less than 1 mm was 14%. Sensitivity for capsular penetration more than 1 mm was 71%. Accuracy for differentiating a pT2 from a pT3 tumor was 68%. Results from this study indicate that the accuracy of the technique was not satisfactory for predicting actual tumor volume. Tumor detection and localization was more accurate in the peripheral zone than in the central zone. Accuracy was poor for detecting capsular penetration of less than 1 mm, but accuracy was much better for penetration of more than 1 mm. Because recent reports suggest that capsular penetration of less than 1 mm does not adversely affect surgical cure, MR imaging still may be practical in the selection of patients for radical prostatectomy.

Magnetic resonance imaging during intracavitary gynecologic brachytherapy

The cases of three patients, two with Stage III-B and one with Stage Il-B carcinoma of the cervix, are cited to illustrate specific advantages of magnetic resonance (MR) imaging over computed tomography (CT) during intracavitary cavitary gynecologic brachytherapy. CT and MR were performed during the first two intracavitary implants. To obtain artifact-free images with the intracavitary implant in place, a CT- and MR-compatible Fletcher system applicator was used. Although CT failed to differentiate the cervical tumor clearly from surrounding tissues, the area of pathology could be identified on MR by comparing the T1-weighted (T1W) and T2-weighted (T2W) images. Cervical tumors typically exhibit low-signal intensity on T1W and high-signal intensity on T2W scans, whereas paracervical soft tissues demonstrate high intensity on both T1W and T2W images. This contrast permits the size, location, and paracervical involvemnt of the tumor to be defined by MR. Multiplanar images obtained during the patient's intracavitary brachytherapy help demonstrate the actual relationship between the tumor and the applicator. Isodose distributions displayed on these images show that, in two cases, the tumor margin extended beyond he prescribed isodose lines. Thus, MR may prove to be a clinically useful reference during intracavitary brachytherapy for ascertaining radiaton dose to actual tumor volume.

Enhancement of tumor proteolysis by TNF-alpha: correlation of in vivo isotope estimates with growth

To evaluate the accuracy of in vivo estimates of protein synthesis and breakdown, measurements of plasma and tissue leucine kinetics were made in rat tumor tissues at different conditions of growth by use of constant intravenous infusion of [14C]leucine. These measurements were made in Yoshida sarcoma tumors on days 10 and 13 after implantation, with and without tumor necrosis factor (TNF) infusion and on day 10 in Walker-256 carcinosarcoma. Expressed as micromoles of leucine per gram tissue, tumor protein breakdown increased (P less than 0.01) from 0.32 +/- 0.02 to 0.52 +/- 0.09 (SE) mumol/h, with progress of the Yoshida sarcoma tumor between days 10 and 13 after implantation. Similarly, TNF increased tumor proteolysis on day 10 (0.43 +/- 0.03 mumol.h-1.g-1, P less than 0.05 vs. day 10 control) but not on day 13 after implantation of the Yoshida tumor. Estimates of growth derived from the difference between protein synthesis and breakdown rates were not statistically different from those based on actual tumor volume changes in both tumor models. However, estimates of "whole body" protein metabolism (plasma leucine flux) were not affected either by tumor aging or by treatment with TNF. This study shows that in vivo estimates of tissue protein metabolism based on our [14C]leucine constant infusion model closely reflect the growth characteristic of that tissue. A cytotoxic perfusion-independent effect for intravenous TNF on growing tumor tissue is demonstrable as increased protein breakdown. Furthermore, the commonly used concept of whole body protein metabolism, derived solely from tracer dilution in plasma, is an oversimplification.