Peter Faulhaber

Positron Emission Tomography for Evaluating Para-aortic Nodal Metastasis in Locally Advanced Cervical Cancer Before Surgical Staging: A Surgicopathologic Study

PURPOSE Positron emission tomographic (PET) scanning provides a novel means of imaging malignancies. This prospective study was undertaken to evaluate PET scanning in detecting para-aortic nodal metastasis in patients with locally advanced cervical carcinoma and no evidence of extrapelvic disease before planned surgical staging lymphadenectomy. MATERIALS AND METHODS After 20 mCi of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) were administered intravenously, the abdomen and pelvis were scanned. Continuous bladder irrigation was used to reduce artifact. Patients were classified by the presence or absence of FDG uptake in the primary tumor and in pelvic or para-aortic nodes. Para-aortic node metastases were classified as present or absent according to a standardized staging procedure. Pelvic node metastases were similarly classified in a subset of patients who underwent pelvic node resection. RESULTS Thirty-two patients with stage IIB (n = 6), IIIB (n = 24), and IVA (n = 2) tumors were studied. Fluorodeoxyglucose was taken up by 91% of the cervical tumors. Six of eight patients with positive para-aortic node metastasis had PET scan evidence of para-aortic nodal metastasis. One of the two false-negatives had only one microscopic focus of metastatic cancer. In the para-aortic nodes, PET scanning had a sensitivity of 75%, a specificity of 92%, a positive predictive value of 75%, and a negative predictive value of 92%. Fluorodeoxyglucose para-aortic nodal uptake conferred a relative risk of 9.0 (95% confidence interval, 2.3 to 36.0) for para-aortic nodal metastasis. All 10 of 17 patients with metastasis were predicted by PET scanning (P < .001); five of these patients had abnormalities on computed tomographic scans. CONCLUSION Cervical cancers have a high avidity for FDG. The use of PET-FDG scanning accurately predicts both the presence and absence of pelvic and para-aortic nodal metastatic disease.

What is the best way to contour lung tumors on PET scans? Multiobserver validation of a gradient-based method using a NSCLC digital PET phantom.

PURPOSE To evaluate the accuracy and consistency of a gradient-based positron emission tomography (PET) segmentation method, GRADIENT, compared with manual (MANUAL) and constant threshold (THRESHOLD) methods. METHODS AND MATERIALS Contouring accuracy was evaluated with sphere phantoms and clinically realistic Monte Carlo PET phantoms of the thorax. The sphere phantoms were 10-37 mm in diameter and were acquired at five institutions emulating clinical conditions. One institution also acquired a sphere phantom with multiple source-to-background ratios of 2:1, 5:1, 10:1, 20:1, and 70:1. One observer segmented (contoured) each sphere with GRADIENT and THRESHOLD from 25% to 50% at 5% increments. Subsequently, seven physicians segmented 31 lesions (7-264 mL) from 25 digital thorax phantoms using GRADIENT, THRESHOLD, and MANUAL. RESULTS For spheres <20 mm in diameter, GRADIENT was the most accurate with a mean absolute % error in diameter of 8.15% (10.2% SD) compared with 49.2% (51.1% SD) for 45% THRESHOLD (p < 0.005). For larger spheres, the methods were statistically equivalent. For varying source-to-background ratios, GRADIENT was the most accurate for spheres >20 mm (p < 0.065) and <20 mm (p < 0.015). For digital thorax phantoms, GRADIENT was the most accurate (p < 0.01), with a mean absolute % error in volume of 10.99% (11.9% SD), followed by 25% THRESHOLD at 17.5% (29.4% SD), and MANUAL at 19.5% (17.2% SD). GRADIENT had the least systematic bias, with a mean % error in volume of -0.05% (16.2% SD) compared with 25% THRESHOLD at -2.1% (34.2% SD) and MANUAL at -16.3% (20.2% SD; p value <0.01). Interobserver variability was reduced using GRADIENT compared with both 25% THRESHOLD and MANUAL (p value <0.01, Levenes test). CONCLUSION GRADIENT was the most accurate and consistent technique for target volume contouring. GRADIENT was also the most robust for varying imaging conditions. GRADIENT has the potential to play an important role for tumor delineation in radiation therapy planning and response assessment.

Elimination of artifactual accumulation of FDG in PET imaging of colorectal cancer

BACKGROUND Positron emission tomography (PET) with fluorine-18 labeled deoxyglucose (FDG) can detect tumor recurrences in surgical patients that are otherwise difficult to assess by CT, as well as distant metastases and small malignant nodes that are not identified by other imaging modalities. However, the evaluation of such malignancy is complicated by urinary and colonic concentrations of FDG. Methods and examples of the elimination of artifactual accumulation of FDG in PET imaging of the abdomen and pelvis are presented. METHODS Elimination of artifactual accumulation requires patient preparation that begins with cleansing of the colon using an isosmotic solution taken the evening prior to examination. Approximately 500 MBq of F-18 FDG is intravenously administered upon arrival at the PET facility and then the patient is hydrated. After administration of furosemide, a Foley catheter with a drainage bag is placed and the patient is then scanned. Just prior to scanning over the pelvis, normal saline is delivered retrogradely into the urinary bladder. At the end of scanning, the patient voids and repeated pelvic images are obtained. RESULTS These routines yield a clean scanning field. Lesions that will generally be missed because they are obscured by FDG accumulations along the colon or in the kidneys, ureters, or bladder are better visualized and identified with greater confidence. Artifacts that lead to misinterpretation also are reduced. CONCLUSION Elimination of artifactual accumulation of FDG in the colon and urinary system is essential if primary cancer, associated adenopathy, or subtle recurrences are to be evaluated in FDG PET imaging of the abdomen and pelvis.

Radiochemotherapy plus 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) in advanced-stage cervical and vaginal cancers ☆ ☆☆

OBJECTIVE Cervical and vaginal cancers have virally-mediated or mutated defects in DNA damage repair responses, making these cancers sensible targets for ribonucleotide reductase inhibition during radiochemotherapy. METHODS We conducted a phase II study evaluating 3× weekly 2-hour intravenous 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, 25 mg/m(2)) co-administered with 1× weekly intravenous cisplatin (40 mg/m(2)) and daily pelvic radiation (45 Gy) in women with stage I(B2)-IV(B) cervical (n=22) or stage II-IV vaginal (n=3) cancers. Brachytherapy followed (40 Gy). Toxicity was monitored by common terminology criteria for adverse events (version 3.0). The primary end point of response was assessed by 3-month posttherapy 2-[(18)F] fluoro-2-deoxy-d-glucose positron emission tomography (PET/CT) and clinical examination. RESULTS 3-AP radiochemotherapy achieved clinical responses in 24 (96% [95% confidence interval: 80-99%]) of 25 patients (median follow-up 20 months, range 2-35 months). 23 (96% [95% confidence interval: 80-99%]) of 24 patients had 3-month posttherapy PET/CT scans that recorded metabolic activity in the cervix or vagina equal or less than that of the cardiac blood pool, suggesting complete metabolic responses. The most frequent 3-AP radiochemotherapy-related adverse events included fatigue, nausea, diarrhea, and reversible hematological and electrolyte abnormalities. CONCLUSIONS The addition of 3-AP to cisplatin radiochemotherapy was tolerable and produced high rates of clinical and metabolic responses in women with cervical and vaginal cancers. Future randomized phase II and III clinical trials of 3-AP radiochemotherapy are warranted.

N staging of lung cancer patients with PET/MRI using a three-segment model attenuation correction algorithm: initial experience.

AbstractObjectivesEvaluate the performance of PET/MRI at tissue interfaces with different attenuation values for detecting lymph node (LN) metastases and for accurately measuring maximum standardised uptake values (SUVmax) in lung cancer patients.Materials and MethodEleven patients underwent PET/CT and PET/MRI for staging, restaging or follow-up of suspected or known lung cancer. Four experienced readers determined the N stage of the patients for each imaging method in a randomised blinded way. Concerning metastases, SUVmax of FDG-avid LNs were measured in PET/CT and PET/MRI in all patients. A standard of reference was created with a fifth experienced independent reader in combination with a chart review. Results were analysed to determine interobserver agreement, SUVmax correlation between CT and MRI (three-segment model) attenuation correction and diagnostic performance of the two techniques.ResultsOverall interobserver agreement was high (κ = 0.86) for PET/CT and substantial (κ = 0.70) for PET/MRI. SUVmax showed strong positive correlation (Spearman’s correlation coefficient = 0.93, P < 0.001) between the two techniques. Diagnostic performance of PET/MRI was slightly inferior to that of PET/CT, without statistical significance (P > 0.05).ConclusionsPET/MRI using three-segment model attenuation correction for LN staging in lung cancer shows a strong parallel to PET/CT in terms of SUVmax, interobserver agreement and diagnostic performance.Key Points•F18-FDG PET/MRI shows similar performance to F18-FDG PET/CT in lung cancer N staging. •PET/MRI has substantial interobserver agreement in N staging. •A three-segment model attenuation correction is reliable for assessing the mediastinum.

Qualitative and Quantitative Performance of 18F-FDG-PET/MRI versus 18F-FDG-PET/CT in Patients with Head and Neck Cancer

BACKGROUND AND PURPOSE: MR imaging and PET/CT are integrated in the work-up of head and neck cancer patients. The hybrid imaging technology 18F-FDG-PET/MR imaging combining morphological and functional information might be attractive in this patient population. The aim of the study was to compare whole-body 18F-FDG-PET/MR imaging and 18F-FDG-PET/CT in patients with head and neck cancer, both qualitatively in terms of lymph node and distant metastases detection and quantitatively in terms of standardized uptake values measured in 18F-FDG-avid lesions. MATERIALS AND METHODS: Fourteen patients with head and neck cancer underwent both whole-body PET/CT and PET/MR imaging after a single injection of 18F-FDG. Two groups of readers counted the number of lesions on PET/CT and PET/MR imaging scans. A consensus reading was performed in those cases in which the groups disagreed. Quantitative standardized uptake value measurements were performed by placing spheric ROIs over the lesions in 3 different planes. Weighted and unweighted κ statistics, correlation analysis, and the Wilcoxon signed rank test were used for statistical analysis. RESULTS: κ statistics for the number of head and neck lesion lesions counted (pooled across regions) revealed interreader agreement between groups 1 and 2 of 0.47 and 0.56, respectively. Intrareader agreement was 0.67 and 0.63. The consensus reading provided an intrareader agreement of 0.63. For the presence or absence of metastasis, interreader agreement was 0.85 and 0.70. The consensus reading provided an intrareader agreement of 0.72. The correlations between the maximum standardized uptake value in 18F-FDG-PET/MR imaging and 18F-FDG-PET/CT for primary tumors and lymph node and metastatic lesions were very high (Spearman r = 1.00, 0.93, and 0.92, respectively). CONCLUSIONS: In patients with head and neck cancer, 18F-FDG-PET/MR imaging and 18F-FDG-PET/CT provide comparable results in the detection of lymph node and distant metastases. Standardized uptake values derived from 18F-FDG-PET/MR imaging can be used reliably in this patient population.

Ten-Year Outcomes: The Clinical Utility of Single Photon Emission Computed Tomography/Computed Tomography Capromab Pendetide (Prostascint) in a Cohort Diagnosed With Localized Prostate Cancer

PURPOSE To evaluate the clinical utility of capromab pendetide imaging with single photon emission computed tomography coregistration with computed tomography (SPECT/CT) in primary prostate cancer (CaP) for pretreatment prognostic staging and localization of biologic target volumes (BTV) for individualized image-guided radiotherapy dose escalation (IGRT-DE). METHODS AND MATERIALS Patients consecutively presenting for primary radiotherapy (February 1997 to December 2002), having a clinical diagnosis of localized CaP, were evaluated for tumor stage using conventional staging and SPECT/CT (N=239). Distant metastatic uptake (mets) were identified by SPECT/CT in 22 (9.2%). None of the suspected mets could be clinically confirmed. Thus, all subjects were followed without alteration in disease management. The SPECT/CT pelvic images defined BTV for IGRT-DE (+150% brachytherapy dose) without (n=150) or with (n=89) external radiation of 45 Gy. The National Comprehensive Cancer Network criteria defined risk groups (RG). The median survivor follow-up was 7 years. Biochemical disease-free survival (bDFS) was reported by clinical nadir +2 ng/mL (CN+2) criteria. Statistical analyses included Kaplan-Meier, multivariate analysis, and Concordance-index models. RESULTS At 10-year analyses, overall survival was 84.8% and bDFS was 84.6%. With stratification by RG, CN+2 bDFS was 93.5% for the low-RG (n=116), 78.7% for the intermediate-RG (n=94), and 68.8% for the high-RG (n=29), p=0.0002. With stratification by pretreatment SPECT/CT findings, bDFS was 65.5% in patients with suspected mets (n=22) vs. 86.6% in patients with only localized uptake (n=217), p=0.0014. CaP disease-specific survival (DSS) was 97.7% for the cohort. With stratification by SPECT/CT findings, DSS was 86.4% (with suspected mets) vs. 99.0% (localized only), p=0.0001. Using multivariate analysis, the DSS hazard ratio for SPECT/CT findings (mets vs. localized) was 3.58 (p=0.0026). Concordance-index tests, based on all data, by CN+2 bDFS criteria were 0.710 for RG alone and 0.773 for SPECT/CT + RG. CONCLUSIONS Through long-term outcomes we demonstrate statistically significant bDFS and DSS predictive value for pretreatment capromab pendetide SPECT/CT imaging in primary CaP. Dual clinical utility is demonstrated, using SPECT/CT to define BTV for individualized IGRT-DE.

Image quality and diagnostic performance of a digital PET prototype in patients with oncologic diseases: Initial experience and comparison with analog PET

We report our initial clinical experience for image quality and diagnostic performance of a digital PET prototype scanner with time-of-flight (DigitalTF), compared with an analog PET scanner with time-of-flight (GeminiTF PET/CT). Methods: Twenty-one oncologic patients, mean age 58 y, first underwent clinical 18F-FDG PET/CT on the GeminiTF. The scanner table was then withdrawn while the patient remained on the table, and the DigitalTF was inserted between the GeminiTF PET and CT scanner. The patients were scanned for a second time using the same PET field of view with CT from the GeminiTF for attenuation correction. Two interpreters reviewed the 2 sets of PET/CT images for overall image quality, lesion conspicuity, and sharpness. They counted the number of suggestive 18F-FDG–avid lesions and provided the TNM staging for the 5 patients referred for initial staging. Standardized uptake values (SUVs) and SUV gradients as a measure of lesion sharpness were obtained. Results: The DigitalTF showed better image quality than the GeminiTF. In a side-by-side comparison using a 5-point scale, lesion conspicuity (4.3 ± 0.6), lesion sharpness (4.3 ± 0.6), and diagnostic confidence (3.4 ± 0.7) were better with DigitalTF than with GeminiTF (P < 0.01). In 52 representative lesions, the lesion maximum SUV was 36% higher with DigitalTF than with GeminiTF, lesion–to–blood-pool SUV ratio was 59% higher, and SUV gradient was 51% higher, with good correlation between the 2 scanners. Lesions less than 1.5 cm showed a greater increase in SUV from GeminiTF to DigitalTF than those lesions 1.5 cm or greater. In 5 of 21 patients, DigitalTF showed an additional 8 suggestive lesions that were not seen using GeminiTF. In the 15 restaging patients, the true-negative rate was 100% and true-positive rate was 78% for both scanners. In the 5 patients for initial staging, DigitalTF led to upstaging in 2 patients and showed the same staging in the other 3 patients, compared with GeminiTF. Conclusion: DigitalTF provides better image quality, diagnostic confidence, and accuracy than GeminiTF. DigitalTF may be the most beneficial in detecting small tumor lesions and disease staging.

Single Photon Emission Computerized Tomography With Capromab Pendetide Plus Computerized Tomography Image Set Co-Registration Independently Predicts Biochemical Failure

PURPOSE We evaluate the usefulness of pretreatment (111)Indium capromab pendetide (ProstaScint) planar imaging (immunoscintigraphy) plus single photon emission tomography co-registration with computerized tomography scans to detect occult metastatic disease and predict for biochemical failure, in a cohort of patients with a clinical diagnosis of localized adenocarcinoma of the prostate referred for primary radiotherapy. MATERIALS AND METHODS Patients were followed after radiotherapy for evidence of biochemical failure using 2 criteria of prostate specific antigen clinical nadir +2 ng/ml and American Society for Therapeutic Radiology and Oncology Consensus definitions. Median followup was 58.8 months (mean 64.8). Clinical risk factors defined 3 risk groups of high (51), intermediate (72) and low (116). RESULTS Overall biochemical failure was 18.3% vs 11.8% by the 2-BFC at 8-year actuarial analysis with 58.8 months median followup. By the CN +2 definition the control date for the cohort is 34.8 months. Pretreatment SPECT/CT suggested prostate cancer metastasis (22), seminal vesicle extension (20) and organ confined disease (197). Biochemical failure in patients having extra-periprostatic metastatic prostate cancer, seminal vesicle extension and organ confined disease uptake on SPECT/CT was 43.2%, 16.0% vs 14.7% (p = 0.0006); and 33.3%, 15.0% vs 8.7% (p = 0.0017) by the 2-BFC, respectively. Cox multiple regression analysis demonstrated that a finding of extra-periprostatic metastatic prostate on SPECT/CT significantly predicted a 4.2-fold greater risk (p = 0.0012) and a 4.5-fold greater risk (p = 0.0011) of failure by the 2-BFC than organ confined disease adjusting for treatment and risk group. CONCLUSIONS Unconfirmed findings of extra-periprostatic metastatic prostate cancer on SPECT/CT immunoscintigraphy independently and significantly predicted an increased risk of biochemical failure in patients presenting for radiotherapy with a clinical diagnosis of localized prostate cancer.

Utility of SPECT/CT for periparotid sentinel lymph node mapping in the surgical management of head and neck melanoma

PURPOSE Sentinel lymph node (SLN) biopsy is instrumental in staging and treatment of cutaneous melanoma. SPECT/CT, single-photon emission computed tomography (SPECT) integrated with computed tomography (CT), increases the accuracy of SLN mapping to improve surgical planning. SPECT/CT can correct for signal scatter to prevent masking, which is especially common in the head and neck. For periparotid lymph nodes SPECT/CT may improve localization of SLNs compared to lymphoscintigraphy. MATERIALS/METHODS Hospital charts were reviewed for 14 patients with melanoma and suspected lymphatic drainage to the parotid region who received lymphoscintigraphy followed by SPECT/CT prior to surgical excision and SLN. RESULTS Overall, SPECT/CT provided data, which changed management in 57% of patients. CONCLUSIONS Fifty-seven percent of our patients benefited from use of SPECT/CT. The distinction between level II and parotid sentinel lymph nodes was clearly identified through SPECT/CT images. We believe that patients with melanoma draining to the parotid region would benefit from SPECT/CT SLN mapping.