Larger Tumor Size and Elevated Serum Chromogranin A Levels Predict Metastatic Disease on DOTATATE Imaging in Patients with Gastroenteropancreatic Neuroendocrine Tumors.

PURPOSE: DOTATATE PET/CT (DOTATATE) is superior to conventional imaging in detecting metastasis for gastroenteropancreatic neuroendocrine tumors (GEP-NETs). However, limited availability, high-cost, and additive radiation exposure necessitate guidelines for its use. This study seeks to investigate the relationship between clinical characteristics and metastasis on DOTATATE. METHODS: This was a retrospective analysis of 815 patients who underwent DOTATATE at UCLA from 2014 to 2022. After applying inclusion and exclusion criteria, the study cohort consisted of 163 patients with pathologically diagnosed GEP-NETs, who either underwent primary tumor resection within 1-year prior, or had not undergone resection at the time of DOTATATE imaging. The presence of metastasis was determined using DOTATATE. Fisher's exact test, chi-squared test, and Mann-Whitney test were conducted to compare intergroup difference. Multivariate analysis was performed to identify clinical characteristics associated with metastasis on DOTATATE. RESULTS: Of patients with GEP-NETs, 40.5% (n = 66) were diagnosed with metastases by using DOTATATE. Those with metastatic disease were more likely to exhibit a larger primary tumor size (median 3.4 vs. 1.2, cm, P < 0.001), elevated serum chromogranin A level (CgA, median 208 vs. 97, mg/ml, P = 0.005), and higher tumor grade (P < 0.001). Primary tumor size ≥2 cm and serum CgA level ≥150 ng/mL for metastatic disease had a sensitivity and specificity of 64% and 89%, and 72% and 59%, respectively. Multivariate analysis demonstrated that primary tumor size (≥2/<2, cm, odds ratio [OR] 47.90, P < 0.001), tumor functionality (functional/nonfunctional, adjusted OR 10.17 P = 0.008), serum CgA level (≥150/<150, ng/ml, OR 6.25, P = 0.005), and tumor grade G2 (G2/G1, OR 9.6, P < 0.001) were independently associated with metastases on DOTATATE. CONCLUSIONS: Among patients with GEP-NETs, primary tumor size ≥2 cm, serum CgA level ≥150 ng/mL, and tumor grade G2 are associated with an increased risk of metastases on DOTATATE, and these predictors may be helpful to identify patients where DOTATATE is indicated for complete staging.

CD19/CD20 Bispecific Chimeric Antigen Receptor (CAR) in Naive/Memory T Cells for the Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma.

To address antigen escape and loss of T-cell functionality, we report a phase I clinical trial (NCT04007029) evaluating autologous naive and memory T (TN/MEM) cells engineered to express a bispecific anti-CD19/CD20 chimeric antigen receptor (CAR; CART19/20) for patients with relapsed/refractory non-Hodgkin lymphoma (NHL), with safety as the primary endpoint. Ten patients were treated with 36 × 106 to 165 × 106 CART19/20 cells. No patient experienced neurotoxicity of any grade or over grade 1 cytokine release syndrome. One case of dose-limiting toxicity (persistent cytopenia) was observed. Nine of 10 patients achieved objective response [90% overall response rate (ORR)], with seven achieving complete remission [70% complete responses (CR) rate]. One patient relapsed after 18 months in CR but returned to CR after receiving a second dose of CART19/20 cells. Median progression-free survival was 18 months and median overall survival was not reached with a 17-month median follow-up. In conclusion, CART19/20 TN/MEM cells are safe and effective in patients with relapsed/refractory NHL, with durable responses achieved at low dosage levels. SIGNIFICANCE: Autologous CD19/CD20 bispecific CAR-T cell therapy generated from TN/MEM cells for patients with NHL is safe (no neurotoxicity, maximum grade 1 cytokine release syndrome) and demonstrates strong efficacy (90% ORR, 70% CR rate) in a first-in-human, phase I dose-escalation trial. This article is highlighted in the In This Issue feature, p. 517.

3'-deoxy-3'-[18F]fluorothymidine positron emission tomography for response assessment in soft tissue sarcoma: a pilot study to correlate imaging findings with tissue thymidine kinase 1 and Ki-67 activity and histopathologic response.

BACKGROUND: This study sought to determine whether [(18)F]fluorothymidine (FLT) positron emission tomography (PET)/computed tomography (CT) imaging allows assessment of tumor viability and proliferation in patients with soft tissue sarcomas who are treated with neoadjuvant therapy. METHODS: Twenty patients with biopsy-proven, resectable, high-grade soft tissue sarcoma underwent [(18)F]FLT PET/CT imaging before and after neoadjuvant therapy. Histologic subtypes included sarcomas not otherwise specified (n = 5), malignant peripheral nerve sheath tumors (n = 3), gastrointestinal stromal tumors (n = 3), leiomyosarcomas (n = 3), angiosarcomas (n = 2), and others (n = 4). Changes in [(18)F]FLT peak standardized uptake value (SUVpeak) were correlated with percent necrosis in excised tissue, whereas posttreatment [(18)F]FLT tumor uptake was correlated with thymidine kinase 1 (TK1) expression and Ki-67 staining indices in excised tumor tissue. RESULTS: Tumor FLT SUVpeak averaged 7.1 ± 3.7 g/mL (range, 1.9-16.1 g/mL) at baseline and decreased significantly to 2.7 ± 1.6 g/mL (range, 0.8-6.0 g/mL) at follow-up (P < .001); however, marked reductions in SUV were not specific for histopathological response. The posttreatment SUVpeak did not correlate with TK1 (P = .27) or Ki-67 expression (P = .21). CONCLUSIONS: Marked reductions in [(18)F]FLT tumor uptake in response to neoadjuvant treatment were observed in most patients with sarcoma. However, these reductions were not specific for histopathologic response to neoadjuvant therapy. Furthermore, posttreatment [(18)F]FLT tumor uptake was unrelated to tumor proliferation by Ki-67 and TK1 staining. These results question the value of [(18)F]FLT PET imaging for treatment response assessments in patients with soft tissue sarcoma.

Discovery and characterization of circulating tumor cell clusters in neuroendocrine tumor patients using nanosubstrate-embedded microchips.

Circulating tumor cell (CTC) clusters are present in cancer patients with severe metastasis, resulting in poor clinical outcomes. However, CTC clusters have not been studied as extensively as single CTCs, and the clinical utility of CTC clusters remains largely unknown. In this study, we aim sought to explore the feasibility of NanoVelcro Chips to simultaneously detect both single CTCs and CTC clusters with negligible perturbation to their intrinsic properties in neuroendocrine tumors (NETs). We discovered frequent CTC clusters in patients with advanced NETs and examined their potential roles, together with single NET CTCs, as novel biomarkers of patient response following peptide receptor radionuclide therapy (PRRT). We observed dynamic changes in both total NET CTCs and NET CTC cluster counts in NET patients undergoing PRRT which correlated with clinical outcome. These preliminary findings suggest that CTC clusters, along with single CTCs, offer a potential non-invasive option to monitor the treatment response in NET patients undergoing PRRT.

FDG-PET/CT imaging predicts histopathologic treatment responses after the initial cycle of neoadjuvant chemotherapy in high-grade soft-tissue sarcomas.

PURPOSE: In patients with soft-tissue sarcoma (STS), the early assessment of treatment responses is important. Using positron emission tomography/computed tomography (PET/CT) with [(18)F]fluorodeoxyglucose (FDG), we determined whether changes in tumor FDG uptake predict histopathologic treatment responses in high-grade STS after the initial cycle of neoadjuvant chemotherapy. EXPERIMENTAL DESIGN: From February 2006 to March 2008, 50 patients with resectable high-grade STS scheduled for neoadjuvant therapy and subsequent tumor resection were enrolled prospectively. FDG-PET/CT before (baseline), after the first cycle (early follow-up), and after completion of neoadjuvant therapy (late follow-up) was done. Tumor FDG uptake and changes were measured by standardized uptake values. Histopathologic examination of the resected specimen provided an assessment of treatment response. Patients with > or = 95% pathologic necrosis were classified as treatment responders. FDG-PET/CT results were compared with histopathologic findings. RESULTS: At early follow-up, FDG uptake decreased significantly more in 8 (16%) responders than in the 42 (84%) nonresponders (-55% versus -23%; P = 0.002). All responders and 14 of 42 nonresponders had a > or = 35% reduction in standardized uptake value between baseline and early follow-up. Using a > or = 35% reduction in FDG uptake as early metabolic response threshold resulted in a sensitivity and specificity of FDG-PET for histopathologic response of 100% and 67%, respectively. Applying a higher threshold at late follow-up improved specificity but not sensitivity. CT had no value at response prediction. CONCLUSION: A 35% reduction in tumor FDG uptake at early follow-up is a sensitive predictor of histopathologic tumor response. Early treatment decisions such as discontinuation of chemotherapy in nonresponding patients could be based on FDG-PET criteria.

FDG-PET/CT Imaging Predicts Histopathologic Treatment Responses after Neoadjuvant Therapy in Adult Primary Bone Sarcomas.

Purpose. The aim of this study was to prospectively evaluate whether FDG-PET allows an accurate assessment of histopathologic response to neoadjuvant treatment in adult patients with primary bone sarcomas. Methods. Twelve consecutive patients with resectable, primary high grade bone sarcomas were enrolled prospectively. FDG-PET/CT imaging was performed prior to the initiation and after completion of neoadjuvant treatment. Imaging findings were correlated with histopathologic response. Results. Histopathologic responders showed significantly more pronounced decreases in tumor FDG-SUVmax from baseline to late follow up than non-responders (64 +/- 19% versus 29 +/- 30 %, resp.; P = .03). Using a 60% decrease in tumor FDG-uptake as a threshold for metabolic response correctly classified 3 of 4 histopathologic responders and 7 of 8 histopathologic non-responders as metabolic responders and non-responders, respectively (sensitivity, 75%; specificity, 88%). Conclusion. These results suggest that changes in FDG-SUVmax at the end of neoadjuvant treatment can identify histopathologic responders and non-responders in adult primary bone sarcoma patients.

Combined assessment of metabolic and volumetric changes for assessment of tumor response in patients with soft-tissue sarcomas.

UNLABELLED: By allowing simultaneous measurements of tumor volume and metabolic activity, integrated PET/CT opens up new approaches for assessing tumor response to therapy. The aim of this study was to determine whether combined assessment of tumor volume and metabolic activity improves the accuracy of (18)F-FDG PET for predicting histopathologic tumor response in patients with soft-tissue sarcomas. METHODS: Twenty patients with locally advanced high-grade soft-tissue sarcoma (10 men and 10 women; mean age, 49 +/- 17 y) were studied by (18)F-FDG PET/CT before and after preoperative therapy. CT tumor volume (CTvol) was measured by delineating tumor borders on consecutive slices of the CT scan. Mean and maximum (18)F-FDG standardized uptake value within this volume (SUVmean and SUVmax, respectively) were determined. Two indices of total lesion glycolysis (TLG) were calculated by multiplying tumor volume by SUVmean (TLGmean) and SUVmax (TLGmax). Changes in CTvol, SUVmean, SUVmax, TLGmean, and TLGmax after chemotherapy were correlated with histopathologic tumor response (> or =95% treatment-induced tumor necrosis). Accuracy for predicting histopathologic response was compared by receiver-operating-characteristic (ROC) curve analysis. RESULTS: Baseline SUVmax, SUVmean, CTvol, TLGmean, and TLGmax were 11.22 g/mL, 2.84 g/mL, 544.1 mL, 1,619.8 g, and 8852.9 g, respectively. After neoadjuvant therapy, all parameters except CTvol showed a significant decline (DeltaSUVmax = -51%, P < 0.001; DeltaSUVmean = -40%, P < 0.001; DeltaCTvol = -14%, P = 0.37; DeltaTLGmean = -44%, P = 0.006; and DeltaTLGmax = -54%, P = 0.001). SUV changes in histopathologic responders (n = 6) were significantly more pronounced than those in nonresponders (n = 14) (P = 0.001). Histopathologic response was well predicted by changes in SUVmean and SUVmax (area under ROC curve [AUC] = 1.0 and 0.98, respectively) followed by TLGmean (AUC = 0.77) and TLGmax (AUC = 0.74). In contrast, changes in CTvol did not allow prediction of treatment response (AUC = 0.48). CONCLUSION: In this population of patients with sarcoma, TLG was less accurate in predicting tumor response than were measurements of the intratumoral (18)F-FDG concentration (SUVmax, SUVmean). Further evaluation of TLG in larger patient populations and other tumor types is necessary to determine the value of this conceptually attractive parameter for assessing tumor response.

Treatment monitoring by 18F-FDG PET/CT in patients with sarcomas: interobserver variability of quantitative parameters in treatment-induced changes in histopathologically responding and nonresponding tumors.

UNLABELLED: Measurements of tumor glucose use by (18)F-FDG PET need to be standardized within and across institutions. Various parameters are used for measuring changes in tumor glucose metabolic activity with (18)F-FDG PET in response to cancer treatments. However, it is unknown which of these provide the lowest variability between observers. Knowledge of the interobserver variability of quantitative parameters is important in sarcomas as these tumors are frequently large and demonstrate heterogeneous (18)F-FDG uptake. METHODS: A total of 33 patients (16 men, 17 women; mean age, 47 +/- 18 y) with high-grade sarcomas underwent (18)F-FDG PET/CT scans before and after neoadjuvant chemotherapy. Two independent investigators measured the following parameters on the pretreatment and posttreatment scans: maximum standardized uptake value (SUVmax), peak SUV (SUVpeak), mean SUV (SUVmean), SUVmean in an automatically defined volume (SUVauto), and tumor-to-background ratio (TBR). The variability of the different parameters was compared by concordance correlation coefficient (CCC), variability effect coefficient, and Bland-Altman plots. RESULTS: Baseline SUVmax, SUVpeak, SUVmean, SUVauto, and TBR averaged 10.36, 7.78, 4.13, and 6.22 g/mL and 14.67, respectively. They decreased to 5.36, 3.80, 1.79, and 3.25 g/mL and 6.62, respectively, after treatment. SUVmax, SUVpeak, and SUVauto measurements and their changes were reproducible (CCC > or = 0.98). However, SUVauto poorly differentiated between responding and nonresponding tumors. The high intratumoral heterogeneity of (18)F-FDG resulted in frequent failure of the thresholding algorithm, which necessitated manual corrections that in turn resulted in a higher interobserver variability of SUVmean (CCCs for follow-up and change were 0.96 and 0.91, respectively; P < 0.005). TBRs also showed a significantly higher variability than did SUVpeak (CCCs for follow-up and change were 0.94 and 0.86, respectively; P < 0.005). CONCLUSION: SUVmax and SUVpeak provided the most robust measurements of tumor glucose metabolism in sarcomas. Delineation of the whole-tumor volume by semiautomatic thresholding did not decrease the variability of SUV measurements. TBRs were significantly more observer-dependent than were absolute SUVs. These findings should be considered for standardization of clinical (18)F-FDG PET/CT trials.

Impact of 68Ga-PSMA-11 PET/CT on the Management of Prostate Cancer Patients with Biochemical Recurrence.

In this prospective survey of referring physicians, we investigated whether and how 68Ga-labeled prostate-specific membrane antigen 11 (68Ga-PSMA-11) PET/CT affects the implemented management of prostate cancer patients with biochemical recurrence (BCR). Methods: We conducted a prospective survey of physicians (NCT02940262) who referred 161 patients with prostate cancer BCR (median prostate-specific antigen value, 1.7 ng/mL; range, 0.05-202 ng/mL). Referring physicians completed one questionnaire before the scan to indicate the treatment plan without 68Ga-PSMA-11 PET/CT information (Q1; n = 101), one immediately after the scan to denote intended management changes (Q2; n = 101), and one 3-6 mo later to document the final implemented management (Q3; n = 56). The implemented management was also obtained via electronic chart review or patient contact (n = 45). Results: A complete documented management strategy (Q1 + Q2 + implemented management) was available for 101 of 161 patients (63%). Seventy-six of these (75%) had a positive 68Ga-PSMA-11 PET/CT result. The implemented management differed from the prescan intended management (Q1) in 54 of 101 patients (53%). The postscan intended management (Q2) differed from the prescan intended management (Q1) in 62 of 101 patients (61%); however, these intended changes were not implemented in 29 of 62 patients (47%). Pelvic nodal and extrapelvic metastatic disease on 68Ga-PSMA-11 PET/CT (PSMA T0N1M0 and PSMA T0N1M1 patterns) was significantly associated with implemented management changes (P = 0.001 and 0.05). Conclusion: Information from 68Ga-PSMA-11 PET/CT brings about management changes in more than 50% of prostate cancer patients with BCR (54/101; 53%). However, intended management changes early after 68Ga-PSMA-11 PET/CT frequently differ from implemented management changes.

Most of the Intended Management Changes After 68Ga-DOTATATE PET/CT Are Implemented.

In this prospective referring-physician-based survey, we investigated the definite clinical impact of 68Ga-DOTATATE PET/CT on managing patients with neuroendocrine tumors (NETs). Methods: We prospectively studied 130 patients with 68Ga-DOTATATE PET/CT referred for initial or subsequent management decisions (NCT02174679). Referring physicians completed one questionnaire before the scan (Q1) to indicate the treatment plan without PET/CT information, one immediately after review of the imaging report to denote intended management changes (Q2), and one 6 mo later (Q3) to verify whether intended changes were in fact implemented. To further validate the Q3 responses, a systematic electronic chart review was conducted. Results: All 3 questionnaires were completed by referring physicians for 96 of 130 patients (74%). 68Ga-DOTATATE PET/CT resulted in intended management changes (Q2) in 48 of 96 patients (50%). These changes were finally implemented (Q3) in 36 of 48 patients (75%). Q3 responses were confirmed in all patients with an available electronic chart (36/96; 38%). Conclusion: This prospective study confirmed a significant impact of 68Ga-DOTATATE PET/CT on the intended management of patients with NETs (50% of changes) and notably demonstrated a high implementation rate (75%) of these intended management changes.

Comparison between 18F-FDG PET, in-line PET/CT, and software fusion for restaging of recurrent colorectal cancer.

UNLABELLED: The aim of this study was to compare PET with (18)F-FDG PET, in-line PET/CT, and software fusion of independently acquired CT and PET scans for staging of recurrent colorectal cancer (CRC). METHODS: Fifty-one patients with suspected recurrent CRC were studied with in-line PET/CT. Thirty-four of these patients underwent an additional CT scan of the chest or abdomen within 4 wk of PET/CT. Software fusion of PET and CT was performed using a fully automated, intensity-based algorithm. The accuracy of the coregistration of PET and CT scans was evaluated by measuring the distance between landmarks visible in the PET and CT images. Histologic evaluation and follow-up for 6 mo served as the gold standard for the presence or absence of recurrent CRC. RESULTS: On a patient basis, the accuracy of staging was significantly higher for in-line PET/CT than for PET (88% vs. 71%, P = 0.01). Software fusion of the independently acquired PET and CT images was unsuccessful in 8 patients (24%). In the remaining patients, the mean distance between 62 landmarks visible in PET and CT was 12.9 +/- 7.9 mm, whereas it was only 7.7 +/- 4.7 mm for in-line PET/CT (P < 0.001). CONCLUSION: In patients with suspected recurrent CRC, in-line PET/CT significantly improves staging compared with PET alone. Due to its high failure rate, software fusion of independently acquired PET and CT studies cannot be considered to represent an alternative to in-line PET/CT.

68Gallium- and 90Yttrium-/ 177Lutetium: "theranostic twins" for diagnosis and treatment of NETs.

Abundant expression of somatostatin receptors (SSTR) is frequently identified in differentiated neuroendocrine tumors and may serve as potential target for diagnostic imaging and treatment. This article discusses the "theranostic approach" of SSTR-targeting compounds including an overview of its role for diagnosis, staging and restaging, discussing its way to being established in clinical routine, and giving an outlook about further potentially relevant developments.

Impact of 68Ga-DOTATATE PET/CT on the management of neuroendocrine tumors: the referring physician's perspective.

UNLABELLED: Somatostatin receptor imaging with (68)Ga-DOTATATE PET/CT (DOTATATE) is increasingly used for managing patients with neuroendocrine tumors. The objective of this study was to determine referring physicians' perspectives on the impact of DOTATATE on the management of neuroendocrine tumors. METHODS: A set of 2 questionnaires (pre-PET and post-PET) was sent to the referring physicians of 100 consecutive patients with known or suspected neuroendocrine tumors, who were evaluated with DOTATATE. Questionnaires on 88 patients were returned (response rate, 88%). Referring physicians categorized the DOTATATE findings on the basis of the written PET reports as negative, positive, or equivocal for disease. The likelihood for metastatic disease was scored as low, moderate, or high. The intended management before and changes as a consequence of the PET study were indicated. RESULTS: The indications for PET/CT were initial and subsequent treatment strategy assessments in 14% and 86% of patients, respectively. Referring physicians reported that DOTATATE led to a change in suspicion for metastatic disease in 21 patients (24%; increased and decreased suspicion in 9 [10%] and 12 [14%] patients, respectively). Intended management changes were reported in 53 of 88 (60%) patients. Twenty patients (23%) scheduled to undergo chemotherapy were switched to treatments without chemotherapy, and 6 (7%) were switched from watch-and-wait to other treatment strategies. Conversely, 5 patients (6%) were switched from their initial treatment strategy to watch-and-wait. CONCLUSION: This survey of referring physicians demonstrates a substantial impact of DOTATATE on the intended management of patients with neuroendocrine tumors.

Clinical use of bone-targeting radiopharmaceuticals with focus on alpha-emitters.

Various single or multi-modality therapeutic options are available to treat pain of bone metastasis in patients with prostate cancer. Different radionuclides that emit ß-rays such as (153)Samarium and (89)Strontium and achieve palliation are commercially available. In contrast to ß-emitters, (223)Radium as a α-emitter has a short path-length. The advantage of the α-emitter is thus a highly localized biological effect that is caused by radiation induced DNA double-strand breaks and subsequent cell killing and/or limited effectiveness of cellular repair mechanisms. Due to the limited range of the α-particles the bone surface to red bone marrow dose ratio is also lower for (223)Radium which is expressed in a lower myelotoxicity. The α emitter (223)Radium dichloride is the first radiopharmaceutical that significantly prolongs life in castrate resistant prostate cancer patients with wide-spread bone metastatic disease. In a phase III, randomized, double-blind, placebo-controlled study 921 patients with castration-resistant prostate cancer and bone metastases were randomly assigned. The analysis confirmed the (223)Radium survival benefit compared to the placebo (median, 14.9 mo vs 11.3 mo; P < 0.001). In addition, the treatment results in pain palliation and thus, improved quality of life and a delay of skeletal related events. At the same time the toxicity profile of (223)Radium was favourable. Since May 2013, (223)Radium dichloride (Xofigo(®)) is approved by the US Food and Drug Administration.

Perceived misinterpretation rates in oncologic 18F-FDG PET/CT studies: a survey of referring physicians.

UNLABELLED: Because only pathologic examination can confirm the presence or absence of malignant disease in cancer patients, a certain rate of misinterpretation in any kind of imaging study is inevitable. For the accuracy of interpretation to be improved, determination of the nature, causes, and magnitude of this problem is needed. This study was designed to collect pertinent information from physicians referring patients for oncologic (18)F-FDG PET/CT. METHODS: A total of 662 referring physicians completed an 11-question survey focused on their experience with the interpretation of oncologic (18)F-FDG PET/CT studies. The participants were oncologists (36.1%; n = 239), hematologists (14.5%; n = 96), radiation oncologists (7.4%; n = 49), surgeons (33.8%; n = 224), and other physicians (8.2%; n = 54). Questions were aimed at determining the frequency, nature, and causes of scan misinterpretations as well as potential solutions to reduce the frequency of misinterpretations. RESULTS: Perceived misinterpretation rates ranged from 5% to 20%, according to most (59.3%) of the participants; 20.8% of respondents reported rates of less than 5%. Overinterpretation rather than underinterpretation was more frequently encountered (68.9% vs. 8.7%, respectively). Limited availability of a patient's history and limited experience of interpreters were the major contributors to this phenomenon, according to 46.8% and 26.7% of the participants, respectively. The actions most commonly suggested to reduce misinterpretation rates (multiple suggestions were possible) were the institution of multidisciplinary meetings (59.8%), the provision of adequate history when ordering an examination (37.4%), and a discussion with imaging specialists when receiving the results of the examination (38.4%). CONCLUSION: Overinterpretation rather than underinterpretation of oncologic (18)F-FDG PET/CT studies prevails in clinical practice, according to referring physicians. Closer collaboration of imaging specialists with referring physicians through more multidisciplinary meetings, improved communication, and targeted training of interpreting physicians are actions suggested to reduce the rates of misinterpretation of oncologic (18)F-FDG PET/CT studies.

Prediction of clinically relevant hyperkalemia in patients treated with peptide receptor radionuclide therapy.

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) is applied in patients with advanced neuroendocrine tumors. Co-infused amino acids (AA) should prevent nephrotoxicity. The aims of this study were to correlate the incidence of AA-induced hyperkalemia (HK) (≥5.0 mmol/l) and to identify predictors of AA-induced severe HK (>6.0). METHODS: In 38 patients, standard activity of (177)Lu-labelled somatostatin analogs was administered. Pre-therapeutic kidney function was assessed by renal scintigraphy and laboratory tests. For kidney protection, AA was co-infused. Biochemical parameters (potassium, glomerular filtration rate, creatinine, blood urea nitrogen (BUN), sodium, phosphate, chloride, and lactate dehydrogenase (LDH)) were obtained prior to 4 and 24 h after the AA infusion. Incidence of HK (≥5.0) was correlated with pre-therapeutic kidney function and serum parameters. Formulas for the prediction of severe hyperkalemia (>6.0) were computed and prospectively validated. RESULTS: At 4 h, HK (≥5.0) was present in 94.7% with severe HK (>6.0) in 36.1%. Values normalized after 24 h in 84.2%. Pre-therapeutic kidney function did not correlate with the incidence of severe HK. Increases in K(+) were significantly correlated with decreases in phosphate (r = -0.444, p < 0.005) and increases in BUN (r = 0.313, p = 0.056). A baseline BUN of >28 mg/dl had a sensitivity of 84.6% and a specificity of 60.0% (AUC = 0.75) in predicting severe HK of >6.0 (phosphate, AUC = 0.37). Computing of five standard serum parameters (potassium, BUN, sodium, phosphate, LDH) resulted in a sensitivity of 88.9% and a specificity of 79.3% for the prediction of severe HK >6.0 (accuracy = 81.6%). CONCLUSIONS: A combination of serum parameters predicted prospectively the occurrence of relevant HK with an accuracy of 81.6% underlining its potential utility for identifying 'high-risk' patients prone to PRRT.

18F-FDG-PET/CT Imaging as an early survival predictor in patients with primary high-grade soft tissue sarcomas undergoing neoadjuvant therapy.

PURPOSE: Neoadjuvant therapy is associated with considerable toxicity and limited survival benefits in patients with soft tissue sarcoma (STS). We prospectively evaluated whether 2[18F]fluoro-2-deoxy-d-glucose ((18)F-FDG)-PET/computed tomographic (CT) imaging after the initial cycle of neoadjuvant therapy could predict overall survival in these patients. EXPERIMENTAL DESIGN: Thirty-nine patients underwent (18)F-FDG-PET/CT before and after one cycle of neoadjuvant therapy. Fifty-six patients underwent end-of-treatment PET. Overall survival was, among others, correlated with changes of SUV(peak) and histopathology. RESULTS: One-, two-, and five-year survival rates were 95% ± 3.0%, 86% ± 4.6%, and 68% ± 6.6%, respectively. Median time to death was 30.9 months (mean, 27.7; range, 6.9-50.1). Optimal cutoff values for early and late decreases in SUV(peak) (26% and 57%, respectively) were significant predictors of survival in univariate survival analysis [P = 0.041; HR, 0.27; 95% confidence interval (CI), 0.08-0.95 and P = 0.045; HR, 0.31; 95% CI, 0.10-0.98]. Seven of 15 early PET nonresponders but only four of 24 early PET responders died during follow-up (P = 0.068). The only other significant survival predictor was surgical margin positivity (P = 0.041; HR, 3.31; 95% CI, 1.05-10.42). By multivariable analysis, early metabolic response (P = 0.016) and positivity of surgical margins (P = 0.036) remained significant survival predictors. CONCLUSION: (18)F-FDG-PET predicted survival after the initial cycle of neoadjuvant chemotherapy in patients with STS and can potentially serve as an intermediate endpoint biomarker in clinical research and patient care.