Search

TPS332 Background: Lutetium-177 [177Lu]-PSMA-617 is a novel radiolabelled small molecule that binds with high affinity to prostate-specific membrane antigen (PSMA), which is commonly overexpressed in prostate cancer. This treatment has demonstrated promising activity and tolerability in men progressing after multiple lines of chemotherapy and endocrine therapy. This trial will determine the activity and safety of 177Lu-PSMA-617 compared to cabazitaxel chemotherapy in men with progressive metastatic castrate resistant prostate cancer. Methods: TheraP is an open-label, randomised, two-arm, multi-centre, phase 2 trial comparing the activity and safety of experimental treatment with [177Lu]-PSMA-617 versus standard 2nd line chemotherapy with cabazitaxel. Key eligibility criteria include prior chemotherapy with docetaxel; rising serum PSA; sufficient PSMA avidity according to central reviewed of imaging with PSMA PET/CT and FDG PET/CT; no discordance between FDG PET and PSMA PET. The trial will include 200 participants randomised in a 1:1 ratio to either [177Lu]-PSMA-617 intravenously every 6 weeks, 8.5 GBq for cycle 1, decreasing by 0.5 GBq with each subsequent cycle, up to maximum 6 cycles (experimental group); or, chemotherapy with cabazitaxel (20 mg/m2) intravenously every 3 weeks, for 10 cycles (standard group). In the event of an exceptional response to [177Lu]-PSMA-617, according to centrally-reviewed, post-therapy SPECT imaging, treatment is suspended but can recommence subsequently on progression. The primary endpoint is a 50% or greater reduction from baseline in serum PSA. Secondary endpoints include overall survival, progression-free survival (PFS), PSA-PFS, pain-PFS, radiographic-PFS, health-related quality of life, pain response, and adverse events. The outcomes of patients excluded because of discordant disease on FDG PET and PSMA PET will be reported as a tertiary objective. The study has accrued 79 of 200 planned participants from 29 January 2018 to 23 October 2018. Clinical trial information: NCT03392428.

We present three patients with lung nodules with an antecedent history of primary cutaneous melanoma or metastasis of melanoma to extrathoracic lymph nodes. Based on radiological findings, it was suspected that these patients had metastatic disease. Subsequent investigations confirmed the cause of the nodules was non-tuberculous mycobacterial infection. We discuss the similarities in symptoms and radiological features between atypical mycobacterial infections and metastatic disease and why a biopsy is important prior to planning a patient's treatment.

Purpose of the report Pancreatic carcinoma is known to demonstrate molecular features of hypoxia. The aim of this prospective pilot study is to analyze the hypoxia agent fluoromisonidazole (FMISO) using PET/CT in pancreatic carcinoma and to compare FMISO activity with glucose metabolism reflected by FDG. Patients and methods Ten patients with pancreatic carcinoma underwent FMISO and FDG PET scans. FMISO and FDG PET/CT scans were analyzed by 2 PET physicians. Regions of interest drawn on the FDG images were transposed to the FMISO images after study coregistration. The FDG SUVmax was used to quantify metabolic activity and FMISO SUVmax and tumor-to-background (muscle) ratio to quantify hypoxia. Results Seven patients were diagnosed with pancreatic adenocarcinoma. The remaining patients had a neuroendocrine tumor, poorly differentiated/sarcomatoid carcinoma, and mucinous neoplasm. Visual analysis demonstrated increased FMISO activity in 2 pancreatic adenocarcinomas. All patients, however, had increased FDG activity at the tumor site. Mean FDG SUVmax was 6 (range: 3.8 to 9.5) compared to 2.3 for FMISO (range: 1 to 3.4). The 2 positive studies on visual analysis of FMISO did not correspond to the largest tumors, the studies with the highest FMISO or FDG SUVmax. There was no significant correlation between FMISO and FDG SUVmax values. Conclusions The hypoxia imaging agent, FMISO, demonstrates minimal activity in pancreatic tumors. If FMISO PET/CT is to be included in clinical trial protocols of hypoxia in pancreatic cancer, it would require correlation with other imaging modalities to localize the tumor and allow semiquantitative analysis.

Early diagnosis and accurate disease staging in patients with malignant pleural mesothelioma (MPM) are essential in classifying such patients into prognostic subgroups to allow delivery of stage-specific therapies. This review addresses the current status of multimodality imaging in the diagnosis and staging of MPM. Clinical, research, and future directions in computed tomography (CT), magnetic resonance imaging, and PET/CT diagnosis and staging of MPM are discussed, including the use of novel PET probes. The article concludes with important take-home messages summarized as the pearls and pitfalls of each diagnostic modality in the diagnosis and staging of patients with MPM.

Assessment of response is important to interpret early phase clinical trial results and to guide individual patient management. In malignant pleural mesothelioma (MPM), the circumferential growth pattern of the disease, the presence of pleural effusion and atelectasis, and the common use of pleurodesis make this a challenging task for imaging specialists and clinicians. This article reviews the current evidence for radiological and positron emission tomography (PET) response assessment in MPM, and the pitfalls and challenges in its application. Current research and future directions in radiological and PET response are discussed, including the use of novel radiotracers.

Imaging of malignant pleural mesothelioma (MPM) poses many challenges for imaging specialists and clinicians due to the anatomic location and unique growth pattern of this tumor. Nevertheless, imaging in MPM plays a critical role in diagnosis, prognostication, prediction or measurement of response to therapy, and monitoring of disease recurrence after aggressive surgical management. Imaging-based studies presented at the 9th International Conference of the International Mesothelioma Interest Group (IMIG) in October 2008 sought to further define the current practice and future potential of imaging for the mesothelioma patient. The Imaging Session was dominated by presentations that addressed the use of fluorodeoxyglucose positron emission tomography (FDG-PET), a clear indication of the expanding role of this modality. These uses included FDG-PET imaging at the point of diagnosis, in prognostication, and in the assessment of response to chemotherapy. Often FDG-PET studies were combined with computed tomography (CT) scans in an attempt to overcome limitations associated with either imaging modality alone. At diagnosis, FDG-PET parameters had a high sensitivity and specificity for differentiation of benign from malignant pleural disease. The use of FDG-PET to extract quantitative features from metabolically active tumor volume was shown to be a significant factor in the prediction of patient survival. The prognostic value of FDG-PET was not confounded by prior talc pleurodesis, despite the inflammatory response associated with the procedure. Metabolic response based on FDG-PET was found to be significantly correlated with progression-free survival. CT-based assessment of mesothelioma was determined to be inconsistent with spherical-model-based criteria so that changes in tumor area, a presumably more complete assessment of tumor burden, exhibited a 46% concordance rate with changes in linear measurements.

Purpose: Existing prognostic systems for malignant pleural mesothelioma do not incorporate imaging information. We aimed to identify the contribution of quantitative fluorodeoxyglucose positron emission tomography (FDG-PET) analysis to other prognostic variables in this disease. Experimental Design: Patients with malignant pleural mesothelioma underwent helical thoracoabdominal computed tomography and FDG-PET scans at baseline. Patients were treated as clinically indicated and followed for survival. FDG-PET variables derived included total glycolytic volume, a composite of tumor volume and glycolytic activity. Results: Ninety-three patients were accrued from 2003 to 2006. Of 89 eligible assessable patients, 28 had undergone pleurodesis before enrolment. Seventeen patients remained alive at analysis; median survival is 15.4 months. On univariate analysis, significant prognostic factors were: total glycolytic volume on FDG-PET (P = 0.003), sarcomatoid histology (P < 0.0005), weight loss (P = 0.031), computed tomography stage (P = 0.015), and European Organization for Research and Treatment of Cancer good prognostic score (P = 0.049). In patients with epithelioid or biphasic histology, baseline total glycolytic volume remained predictive of survival in patients with (P = 0.01) or without (P = 0.018) previous pleurodesis. In multivariate analysis, no variable other than histology contributed to the model in patients with sarcomatoid histology; total glycolytic volume and weight loss contributed to the models in patients with nonsarcomatoid histology. computed tomography–assessed tumor-node-metastasis stage did not contribute to the model. A nomogram, which incorporates quantitative PET parameters and pleurodesis into prognostic information, is presented. Conclusions: Sarcomatoid histology remains the strongest prognostic factor. In patients with non sarcomatoid disease, volumetric FDG-PET parameters are more predictive of survival than tumor-node-metastasis staging, suggesting that tumor volume and glycolytic activity may be more important determinants of prognosis in malignant pleural mesothelioma than anatomic extent of disease. Clin Cancer Res; 16(8); 2409–17. ©2010 AACR.

SUVmax is currently the most common semi-quantitative method of response assessment on FDG PET. By defining the tumour volume of interest (VOI), a measure of total glycolytic volume (TGV) may be obtained. We aimed to comprehensively examine, in a phantom setting, the accuracy of TGV in reflecting actual lesion activity and to compare TGV with SUVmax for response assessment. The algorithms for VOI generation from which TGV was derived included fixed threshold techniques at 50% of maximum (MAX50), 70% of maximum (MAX70), an adaptive threshold of 50% of (maximum + background)/2 (BM50) and a semi-automated iterative region-growing algorithm, GRAB. Comparison with both actual lesion activity and response scenarios was performed. SUVmax correlated poorly with actual lesion activity (r = 0.651) and change in lesion activity (r = 0.605). In a response matrix scenario SUVmax performed poorly when all scenarios were considered, but performed well when only clinically likely scenarios were included. The TGV derived using MAX50 and MAX70 algorithms performed poorly in evaluation of lesion change. The TGV derived from BM50 and GRAB algorithms however performed extremely well in correlation with actual lesion activity (r = 0.993 and r = 0.982, respectively), change in lesion activity (r = 0.972 and r = 0.963, respectively) and in the response scenario matrix. TGV(GRAB) demonstrated narrow confidence bands when modelled with actual lesion activity. Measures of TGV generated by iterative algorithms such as GRAB show potential for increased sensitivity of metabolic response monitoring compared to SUVmax, which may have important implications for improved patient care.

The aim of chemotherapy for mesothelioma is to palliate symptoms and improve survival. Measuring response using CT is challenging because of the circumferential tumor growth pattern. This study aims to evaluate the role of serial (18)F-FDG PET in the assessment of response to chemotherapy in patients with mesothelioma.Patients were prospectively recruited and underwent both (18)F-FDG PET and conventional radiological response assessment before and after 1 cycle of chemotherapy. Quantitative volume-based (18)F-FDG PET analysis was performed to obtain the total glycolytic volume (TGV) of the tumor. Survival outcomes were measured.Twenty-three patients were suitable for both radiological and (18)F-FDG PET analysis, of whom 20 had CT measurable disease. After 1 cycle of chemotherapy, 7 patients attained a partial response and 13 had stable disease on CT assessment by modified RECIST (Response Evaluation Criteria in Solid Tumors) criteria. In the 7 patients with radiological partial response, the median TGV on quantitative PET analysis fell to 30% of baseline (range, 11%-71%). After 1 cycle of chemotherapy, Cox regression analysis demonstrated a statistically significant relationship between a fall in TGV and improved patient survival (P = 0.015). Neither a reduction in the maximum standardized uptake value (P = 0.097) nor CT (P = 0.131) demonstrated a statistically significant association with patient survival.Semiquantitative (18)F-FDG PET using the volume-based parameter of TGV is feasible in mesothelioma and may predict response to chemotherapy and patient survival after 1 cycle of treatment. Therefore, metabolic imaging has the potential to improve the care of patients receiving chemotherapy for mesothelioma by the early identification of responding patients. This technology may also be useful in the assessment of new systemic treatments for mesothelioma.

Introduction To evaluate the detection rate of positive choline PET–CT and its clinical role in assisting with management decisions and the correlation between positive choline PET–CT and clinical/pathological parameters in prostate cancer patients with biochemical relapse following radical prostatectomy. Methods This was a longitudinal observational pilot study of 34 patients who received choline PET–CT scans with biochemical relapse after radical prostatectomy. Variables including peak PSA, PSA doubling time (DT), Gleason score, age, initial PSA at diagnosis, use of ADT prior to PET and initial clinical staging were statistically analysed to assess for independent predictive factors for positive PET findings. Results Choline PET–CT was positive in 38.2% of patients (13/34). The only statistically significant predictor for positive PET–CT was the use of ADT prior to PET–CT, with OR 18.7 (95% CI, 2.87–122.45), P

Purpose: To investigate and compare the quantitative accuracy of 90Y imaging across different generation PET/CT scanners, for the purpose of dosimetry after radioembolization with resin microspheres. Methods: A strict experimental and imaging protocol was followed by 47 international sites using the NEMA 2007/IEC 2008 PET body phantom with an 8-to-1 sphere-to-background ratio of 90Y solution. The phantom was imaged over a 7-day period (activity ranging from 0.5 to 3.0 GBq) and all reconstructed data were analysed at a core laboratory for consistent processing. Quantitative accuracy was assessed through measures of total phantom activity, activity concentration in background and hot spheres, misplaced counts in a nonradioactive insert, and background variability. Results: Of the 69 scanners assessed, 37 had both time-of-flight (ToF) and resolution recovery (RR) capability. These current generation scanners from GE, Philips and Siemens could reconstruct background concentration measures to within 10 % of true values over the evaluated range, with greater deviations on the Philips systems at low count rates, and demonstrated typical partial volume effects on hot sphere recovery, which dominated spheres of diameter 20 mm in diameter, activity concentrations were consistently underestimated by about 20 %. Non-ToF scanners from GE Healthcare and Siemens were capable of producing accurate measures, but with inferior quantitative recovery compared with ToF systems. Conclusion: Current generation ToF scanners can consistently reconstruct 90Y activity concentrations, but they underestimate activity concentrations in small structures (≤37 mm diameter) within a warm background due to partial volume effects and constraints of the reconstruction algorithm. At the highest count rates investigated, measures of background concentration (about 300 kBq/ml) could be estimated on average to within 1 %, 5 % and 2 % for GE Healthcare (all-pass filter, RR + ToF), Philips (4i8s ToF) and Siemens (2i21s all-pass filter, RR + ToF) ToF systems, respectively. Over the range of activities investigated, comparable performance between GE Healthcare and Siemens ToF systems suggests suitability for quantitative analysis in a scenario analogous to that of postradioembolization imaging for treatment of liver cancer., 0, SCOPUS: ar.j, info:eu-repo/semantics/published

For phantom studies involving 90Y PET/CT, homogeneous solutions of 90Y, for example, 90Y citrate, are commonly used. However, the microsphere biodistribution of a postradioembolization liver is never homogeneous; therefore, such phantoms are physiologically unrealistic for simulating clinical scenarios. The aim of this work was to develop a safe and practical phantom capable of simulating the heterogeneous microsphere biodistribution of a postradioembolization liver. Methods: Gelatin (5%) was used to suspend 90Y resin microspheres, poured into plastic containers to simulate a liver with 2 tumors. Microspheres were added while the gelatin was maintained in a liquid state on a hot plate and continuously stirred with magnetic stir bars. The liquid microsphere mixture was then rapidly cooled in an ice bath while being stirred, resulting in a heterogeneous suspension of microspheres. The completed phantom was serially scanned by 90Y PET/CT over 2 wk. Results: All scans demonstrated a heterogeneous microsphere distribution throughout the liver and tumor inserts. Serendipitously, magnetic stir bars left inside the phantom produced CT artifacts similar to those caused by embolization coils, whereas pockets of air trapped within the gelatin during its preparation mimicked gas within hollow viscus. The microspheres and tumor inserts remained fixed and suspended within the gelatin, with no evidence of breakdown or leakage. Conclusion: A gelatin phantom realistically simulating the physiologic microsphere biodistribution of a postradioembolization liver is feasible to construct in a radiopharmacy.

We report a case of a brain abscess identified on fluorine-18 choline (FCH) positron emission tomography (PET) scan, which was not identified on fluorodeoxyglucose (FDG) PET scan. To our knowledge, there are no previous case reports of incidental brain abscess identified by FCH PET imaging. A 51-year-old man, with liver cirrhosis complicated by hepatocellular carcinoma (HCC) was enrolled in a research trial comparing HCC detection in FCH PET versus FDG PET. During the course of the trial, he underwent radiofrequency ablation (RFA) for HCC. A repeat FCH PET scan post-RFA incidentally revealed a 2.5 cm lesion with avid uptake in the left occipital area of the brain. The patient was asymptomatic. MRI suggested this was an abscess. A craniotomy and drainage was performed, with culture of Streptococcus intermedius (S. milleri group) from the thick-walled collection, a causative organism for previous episode of pneumonia. He successfully completed a 6 week course of antibiotics.

Objectives Malignant pleural mesothelioma (MPM) is a chemotherapy resistant tumor with a poor prognosis. Hypoxia is increasingly recognized as an important factor in tumor aggressiveness and cellular resistance to chemotherapy and radiation treatment. This prospective pilot study was performed with [F-18] fluoromisonidazole (FMISO) PET-CT to characterize hypoxia in patients with MPM. Materials and methods Twenty prospectively recruited patients with histologically or cytologically confirmed MPM not currently receiving systemic or local treatment underwent both FMISO and fluorodeoxyglucose (FDG) PET-CT scans within 2 weeks. FMISO and FDG PET-CT scans were independently analyzed visually and semi-quantitatively using SUVmax and tumor to background ratio (TBR) in order to assess tumor hypoxia and metabolic activity. Lesion by lesion analysis was performed in sites of measurable pleural masses. Results Visual analysis demonstrated tumor FMISO activity in 17 of 20 patients, and tumor FDG activity in 19 of 20 patients. Focal areas of bulky tumor were most likely to demonstrate hypoxia. In 19 patients suitable for semi-quantitative analysis the median FDG SUVmax was 6.4 (range 1.9–19.1), median FMISO SUVmax was 2.5 (range 1.4–3.7) and median FMISO TBR was 1.8 (1.1–2.5). There was a positive correlation between intensity of metabolic activity and hypoxia ( r =0.72, p =0.001). Lesion by lesion analysis demonstrated a positive correlation between tumor thickness and FMISO activity ( r =0.77, p Conclusion This pilot study confirms that MPM is a tumor with significant areas of hypoxia, particularly in dominant tumor masses. The relationship of tumor hypoxia to effectiveness of chemotherapy and/or radiation therapy warrants prospective assessment.

Introduction: There is no accepted second-line therapy for patients with advanced malignant pleural mesothelioma (MPM), whose disease has progressed after first-line chemotherapy. The multitargeted tyrosine kinase inhibitor sunitinib malate targets several pathways overexpressed in mesothelioma. This phase II study assessed objective response to sunitinib and correlative biomarkers in patients with progressive pretreated MPM. Methods: Eligible patients had confirmed MPM, radiological progression after chemotherapy, Eastern Cooperative Oncology Group performance status 0 to 1, and measurable disease. Patients received oral sunitinib 50 mg daily for 28 of every 42 days. The primary endpoint was objective radiological response. Patients without prior pleurodesis had fluorodeoxyglucose positron emission tomographic response assessed by total glycolytic volume criteria. Correlative biomarkers included serum mesothelin, vascular endothelial growth factor (VEGF)-A, VEGF-C, interleukin-8, sVEGFR-2, sVEGFR-3, and s-kit. Results: Fifty-three patients received sunitinib between July 2006 and December 2009; 51 were assessable for response. Patients received a median of two cycles (range, 1–12); 40% required dose reduction. Fatigue was the most prominent toxicity. Six patients (12%) had a confirmed radiological partial response, 34 (65%) had stable disease, and 11 (22%) had progressive disease as best response. Six of 20 patients had a decrease in fluorodeoxyglucose positron emission tomographic total glycolytic volume of 15% or more. Median overall survival was 6.1 months, and median time to progression was 3.5 months. Correlative biomarkers did not predict treatment response. Conclusions: Sunitinib has activity in a subset of patients with pretreated MPM. Consideration should be given to different treatment schedules and examination of other biomarkers for further study of sunitinib in MPM.

Purpose: To examine the clinical utility of soluble mesothelin in patients with malignant pleural mesothelioma. Experimental Design: A total of 97 patients (female: 11; male: 86) were prospectively enrolled, longitudinal serum samples collected, and mesothelin concentrations determined. Baseline mesothelin levels were analyzed relative to tumor stage, presence of metastatic disease, the positron emission tomography (PET) parameters maximum standardized uptake value, tumor volume, total glycolytic volume, and survival. Changes in mesothelin level were correlated to objective response to chemotherapy, as assessed radiologically and by PET imaging, and with patient survival. Results: Baseline mesothelin levels greater than 5 nmol/L were a significant negative prognostic indicator (HR = 2.25; 95% CI, 1.20–4.21) and correlated with tumor stage and volume. In 55 patients who received chemotherapy, change in mesothelin correlated with radiological response (χ2 = 11.32; P = 0.023) and change in metabolically active tumor volume (r = 0.58; P < 0.01). Median survival for patients with a reduction in mesothelin following chemotherapy (19 months) was significantly longer than for patients with increased mesothelin (5 months; P < 0.001). Conclusion: These findings show the potential value of changes in mesothelin levels for prognostication and monitoring of treatment response in mesothelioma. Clin Cancer Res; 17(5); 1181–9. ©2010 AACR.

Purpose: There is a need for new treatments for Hodgkin and T-cell lymphoma due to the development of drug resistance in a proportion of patients. This phase I study of radioimmunotherapy used CHT-25, a chimeric antibody to the α-chain of the interleukin-2 receptor, CD25, conjugated to iodine-131 (131I) in patients with refractory CD25-positive lymphomas.Experimental Design: Fifteen patients were treated (Hodgkin lymphoma, 12; angioimmunoblastic T-cell lymphoma, 1; adult T-cell leukemia/lymphoma, 2). Tumor was monitored by computed tomography and in all but two patients by 18F-fluorodeoxyglucose positron emission tomography.Results: There were no grade 3 or 4 infusion reactions. At the maximum tolerated dose of 1,200 MBq/m2, the major side effect was delayed myelotoxicity with the nadir for platelets at 38 days and for neutrophils at 53 days. One patient treated with 2,960 MBq/m2 developed prolonged grade 4 neutropenia and thrombocytopenia and died of Pneumocystis jiroveci pneumonia. Nonhematologic toxicity was mild. Single photon emission computer tomography imaging showed tumor-specific uptake and retention of 131I and no excessive retention in normal organs. Of nine patients receiving ≥1,200 MBq/m2, six responded (three complete response and three partial response); one of six patients with administered radioactivity of ≤740 MBq/m2 had a complete response.Conclusions: CHT-25 is well tolerated with 1,200 MBq/m2 administered radioactivity and shows clinical activity in patients who are refractory to conventional therapies. Phase II studies are justified to determine efficacy and toxicity in a broader range of clinical scenarios. (Clin Cancer Res 2009;15(24):7701–10)

Purpose: Antibody-directed enzyme prodrug therapy is a two-stage treatment whereby a tumor-targeted antibody-enzyme complex localizes in tumor for selective conversion of prodrug. The purpose of this study was to establish optimal variables for single administration of MFECP1, a recombinant antibody-enzyme fusion protein of an anti–carcinoembryonic antigen single-chain Fv antibody and the bacterial enzyme carboxypeptidase G2 followed by a bis-iodo phenol mustard prodrug. MFECP1 is manufactured in mannosylated form to facilitate normal tissue elimination.Experimental Design: Pharmacokinetic, biodistribution, and tumor localization studies were used to test the hypothesis that MFECP1 localizes in tumor and clears from normal tissue via the liver. Firstly, safety of MFECP1 and a blood concentration of MFECP1 that would avoid systemic prodrug activation were tested. Secondly, dose escalation of prodrug was done. Thirdly, the dose of MFECP1 and timing of prodrug administration were optimized.Results: MFECP1 was safe and well tolerated, cleared rapidly via the liver, and was less immunogenic than previously used products. Eighty-fold dose escalation from the starting dose of prodrug was carried out before dose-limiting toxicity occurred. Confirmation of the presence of enzyme in tumor and DNA interstrand cross-links indicating prodrug activation were obtained for the optimal dose and time point. A total of 28 of 31 patients was evaluable for response, the best response being a 10% reduction of tumor diameter, and 11 of 28 patients had stable disease.Conclusions: Optimal conditions for effective therapy were established. A study testing repeat treatment is currently being undertaken.

Functional imaging of cancer adds important information to the conventional measurements in monitoring response. Serial 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), which indicates changes in glucose metabolism in tumours, shows great promise for this. However, there is a need for a method to quantitate alterations in uptake of FDG, which accounts for changes in tumour volume and intensity of FDG uptake. Selection of regions or volumes [ROI or volumes of interest (VOI)] by hand drawing, or simple thresholding, suffers from operator-dependent drawbacks. We present a simple, robust VOI growing method for this application. The method requires a single seed point within the visualised tumour and another in relevant normal tissue. The drawn tumour VOI is insensitive to the operator inconsistency and is, thus, a suitable basis for comparative measurements. The method is validated using a software phantom. We demonstrate the use of the method in the assessment of tumour response in 31 patients receiving chemotherapy for various carcinomas. Valid assessment of tumour response could be made 2–4 weeks after starting chemotherapy, giving information for clinical decision making which would otherwise have taken 9–12 weeks. Survival was predicted from FDG-PET 2–4 weeks after starting chemotherapy (p = 0.04) and after 9–12 weeks FDG-PET gave a better prediction of survival (p = 0.002) than CT or MRI (p = 0.015). FDG-PET using this method of analysis has potential as a routine tool for optimising use of chemotherapy and improving its cost effectiveness. It also has potential for increasing the accuracy of response assessment in clinical trials of novel therapies.

Background Coincidence imaging of low-abundance yttrium-90 (90Y) internal pair production by positron emission tomography with integrated computed tomography (PET/CT) achieves high-resolution imaging of post-radioembolization microsphere biodistribution. Part 2 analyzes tumor and non-target tissue dose-response by 90Y PET quantification and evaluates the accuracy of tumor 99mTc macroaggregated albumin (MAA) single-photon emission computed tomography with integrated CT (SPECT/CT) predictive dosimetry. Methods Retrospective dose quantification of 90Y resin microspheres was performed on the same 23-patient data set in part 1. Phantom studies were performed to assure quantitative accuracy of our time-of-flight lutetium-yttrium-oxyorthosilicate system. Dose-responses were analyzed using 90Y dose-volume histograms (DVHs) by PET voxel dosimetry or mean absorbed doses by Medical Internal Radiation Dose macrodosimetry, correlated to follow-up imaging or clinical findings. Intended tumor mean doses by predictive dosimetry were compared to doses by 90Y PET. Results Phantom studies demonstrated near-perfect detector linearity and high tumor quantitative accuracy. For hepatocellular carcinomas, complete responses were generally achieved at D70 > 100 Gy (D70, minimum dose to 70% tumor volume), whereas incomplete responses were generally at D70 < 100 Gy; smaller tumors ( 100 Gy more easily than larger tumors. There was complete response in a cholangiocarcinoma at D70 90 Gy and partial response in an adrenal gastrointestinal stromal tumor metastasis at D70 53 Gy. In two patients, a mean dose of 18 Gy to the stomach was asymptomatic, 49 Gy caused gastritis, 65 Gy caused ulceration, and 53 Gy caused duodenitis. In one patient, a bilateral kidney mean dose of 9 Gy (V20 8%) did not cause clinically relevant nephrotoxicity. Under near-ideal dosimetric conditions, there was excellent correlation between intended tumor mean doses by predictive dosimetry and those by 90Y PET, with a low median relative error of +3.8% (95% confidence interval, -1.2% to +13.2%). Conclusions Tumor and non-target tissue absorbed dose quantification by 90Y PET is accurate and yields radiobiologically meaningful dose-response information to guide adjuvant or mitigative action. Tumor 99mTc MAA SPECT/CT predictive dosimetry is feasible. 90Y DVHs may guide future techniques in predictive dosimetry.

7036 Background: There is no standard second-line therapy for progressive MPM. Sunitinib is a multi-targeted tyrosine kinase inhibitor of rational targets in MPM including VEGFR and PDGFR. We tested the safety and efficacy of second-line sunitinib in MPM. Methods: Eligible consenting patients (pts) had progressive MPM during or after first-line platinum/antimetabolite, ECOG PS 0-1, adequate organ function, and measurable disease. Treatment: sunitinib 50 mg/day ×28d q6 weeks. Primary endpoint: objective response (OR) defined by either a). Modified RECIST Criteria (MRC) on CT scan or b) metabolic response on FDG-PET in pts without prior talc pleurodesis (J Nuc Med (48) 1449-58; 2007). Imaging was performed at baseline and after cycles 1, 2, and every 2 cycles thereafter; most PET imaging was during treatment break. Simon's 2 stage design: 2 responses in the first 23 pts and 5 responses in 51 assessable pts gave α = 0.05, β = 0.1 assuming an OR of 20% to be of interest. Results: From 05/06 to 12/09 53 eligib...

8063 Background: There is no standard second-line therapy for progressive MPM following first line chemotherapy. Sunitinib is a multi-targeted tyrosine kinase inhibitor of VEGFR, PDGFR, c-Kit and Flt-3. VEGFR and PDGFR are potential targets in MPM. We examined the safety and efficacy of sunitinib as second line treatment in MPM. Methods: Eligible patients had progressive MPM during or after first-line chemotherapy with platinum and antimetabolite, ECOG PS 0–1, adequate organ function, measurable disease, and gave informed consent. Treatment: sunitinib 50 mg/day x28d q6 weeks. Primary endpoint was objective response defined by either a). Modified RECIST Criteria (MRC) on CT scan or b) metabolic response on FDG-PET in patients without prior talc pleuradesis (Francis et al, J Nuc Med (48) 1449–58; 2007). Imaging was performed at baseline and after cycles 1, 2, and every 2 cycles thereafter. Simon’s 2 stage design required 2 responses in 23 patients (stage I) to give α = 0.05, β = 0.1 assuming a true RR of 20...