A Phase II Study of 131I-rituximab for Patients With Relapsed or Refractory Marginal Zone Lymphoma.

Background: Radioimmunotherapy (RIT) is a rare treatment option for relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). We investigated the safety and efficacy of 131I-rituximab in patients with relapsed or refractory marginal zone lymphomas. Methods: Patients with pathologically confirmed marginal zone lymphoma who relapsed or were resistant to prior therapy were enrolled. The patients received 250 mg/m2 of unlabeled rituximab immediately before receiving a therapeutic 131I-rituximab dose. The primary endpoint was the objective response rate (ORR), and the secondary endpoints were toxicity assessment, progression-free survival (PFS), and overall survival (OS). Results: Ten patients (median age = 57.5 years; range = 32-71) were included. Owing to poor enrollment, only 10 of the initially intended 25 patients were included in the study, rendering it unfeasible to perform the primary endpoint analysis. Before RIT, patients received chemotherapy, with 40% (n = 4) receiving rituximab therapy. Median PFS and OS were 18.9 months (95% confidence interval [CI]: 0.0-38.9) and 100.0 months (95% CI: 39.8-160.1), respectively. The ORR was 90%, and the duration of response was 29.7 months (95% CI: 0.0-61.3). Considering a median follow-up of 78.5 months (95% CI: 42.7-114.3), 4 patients (40%) were diagnosed with secondary malignancy. Hematological toxicities were common treatment-related adverse events, and 60% and 50% of the patients experienced grade 3 to 4 thrombocytopenia and neutropenia, respectively. Conclusions: 131I-rituximab showed marked efficacy in patients with relapsed or refractory marginal zone lymphoma, with a considerable risk of secondary malignancies during long-term follow-up. Radioimmunotherapy is not a recommended treatment option for relapsed or refractory marginal zone lymphoma but may be considered when other treatment options are not feasible.

Radioimmunotherapy with 131 I-rituximab for patients with relapsed or refractory follicular or mantle cell lymphoma.

AIM: This study aimed to evaluate the safety and efficacy of 131 I-rituximab in patients with relapsed or refractory follicular or mantle cell lymphoma. METHODS: Twenty-four patients with relapsed or refractory follicular or mantle cell lymphoma were administered unlabeled rituximab (70 mg) immediately before receiving a therapeutic dose of 131 I-rituximab. Contrast-enhanced 18F-fluorodeoxyglucose positron emission tomography/computed tomography was used a month later to assess tumor response. RESULTS: This study enrolled 24 patients between June 2012 and 2022. Depending on how they responded to radioimmunotherapy (RIT), 131 I-rituximab was administered one to five times. Of the 24 patients, 9 achieved complete response after RIT and 8 achieved partial response. The median progression-free and overall survival was 5.9 and 37.9 months, respectively. During the follow-up period of 64.2 months, three patients were diagnosed with a secondary malignancy. Among treatment-related adverse events, hematologic toxicities were common, and grade 3-4 thrombocytopenia and neutropenia were reported in 66.6% of cases. CONCLUSION: 131 I-rituximab has an effective and favorable safety profile in patients with relapsed or refractory follicular lymphoma and mantle cell lymphoma. This suggests that RIT may also be considered a treatment option for patients with relapsed or refractory follicular lymphoma and mantle cell lymphoma.

The role of 18F-FDG PET/CT in patients with diffuse large B-cell lymphoma after radioimmunotherapy using 131I-rituximab as consolidation therapy.

PURPOSE: To evaluate the prognostic value of pretreatment 18F-FDG PET/CT after consolidation therapy of 131I-rituximab in patients with diffuse large B-cell lymphoma (DLBCL) who had acquired complete remission after receiving chemotherapy. METHODS: Patients who were diagnosed with DLBCL via histologic confirmation were retrospectively reviewed. All patients had achieved complete remission after 6 to 8 cycles of R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone) chemotherapy after which they underwent consolidation treatment with 131I-rituximab. 18F-FDG PET/CT scans were performed before R-CHOP for initial staging. The largest diameter of tumor, maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were obtained from pretreatment 18F-FDG PET/CT scans. Receiver-operating characteristic curves analysis was introduced for assessing the optimal criteria. Kaplan-Meier curve survival analysis was performed to evaluate both relapse free survival (RFS) and overall survival (OS). RESULTS: A total of 15 patients (12 males and 3 females) with a mean age of 56 (range, 30-73) years were enrolled. The median follow-up period of these patients was 73 months (range, 11-108 months). Four (27%) patients relapsed. Of them, three died during follow-up. Median values of the largest tumor size, highest SUVmax, MTV, and TLG were 5.3 cm (range, 2.0-16.4 cm), 20.2 (range, 11.1-67.4), 231.51 (range, 15-38.34), and 1277.95 (range, 238.37-10341.04), respectively. Patients with SUVmax less than or equal to 16.9 showed significantly worse RFS than patients with SUVmax greater than 16.9 (5-year RFS rate: 60% vs. 100%, p = 0.008). Patients with SUVmax less than or equal to 16.9 showed significantly worse OS than patients with SUVmax greater than 16.9 (5-year OS rate: 80% vs. 100% p = 0.042). CONCLUSION: Higher SUVmax at pretreatment 18F-FDG PET/CT was associated with better relapse free survival and overall survival in DLBCL patients after consolidation therapy with 131I-rituximab. However, because this study has a small number of patients, a phase 3 study with a larger number of patients is needed for clinical application in the future.

The Prediction of HER2-Targeted Treatment Response Using 64Cu-Tetra-Azacyclododecanetetra-Acetic Acid (DOTA)-Trastuzumab PET/CT in Metastatic Breast Cancer: A Case Report.

A 45-year-old woman diagnosed with breast cancer reported disease progression in the form of metastatic lung and recurrent breast lesions following chemotherapy and human epidermal growth factor receptor 2 (HER2)-targeted therapy. The patient underwent 64Cu-tetra-azacyclododecanetetra-acetic acid (DOTA)-trastuzumab positron emission tomography/computed tomography (PET/CT) to evaluate the HER2 expression status. 64Cu-DOTA-trastuzumab accumulated in the left breast and lymph nodes but not in the lung lesions. Following trastuzumab emtansine treatment, there was a significant improvement in the lesions with 64Cu-DOTA-trastuzumab accumulation. However, the lesions that did not accumulate 64Cu-DOTA-trastuzumab aggravated. Therefore, it was concluded that 64Cu-DOTA-trastuzumab PET/CT can be used to predict the outcome of HER2-targeted treatment by evaluating HER2 expression in breast cancer patients.

The Feasibility of 64Cu-PSMA I&T PET for Prostate Cancer.

Background: The goal of this research was to investigate the feasibility of 64Cu labeling in prostate-specific membrane antigen imaging and therapy (PSMA I&T) for PSMA positron emission tomography (PET) imaging and biodistribution evaluation. Materials and Methods: PSMA I&T was labeled with 64Cu, and stability in human and mouse sera was evaluated. Prostate cancer cell lines were used for specific uptake assays (22RV1 for PSMA-positive, PC-3 for -negative). Both PC-3 and 22RV1 cells were transplanted into the left and right thighs in a mouse for PET/computed tomography (CT) imaging. Biodistribution was performed using 22RV1 tumor models. Results: Labeling yield (decay corrected) of 64Cu-PSMA I&T was more than 95% compared to the free 64Cu peak. The serum stability of 64Cu-PSMA I&T was maintained at more than 90% until 60 h. Regarding the specific binding of 64Cu-PSMA I&T was 7.5-fold higher to 22RV1 cells than PC-3 cells (p < 0.001). On PET/CT imaging, more specific 64Cu-PSMA I&T uptake was observed to 22RV1 tumors than to PC-3 tumors. In the PSMA blocking study using 2-phosphonomethoxypropyl adenine (2-PMPA), the 64Cu-PSMA I&T signal significantly decreased in the 22RV1 tumor region. In the biodistribution study, the kidney uptake was the highest among all organs at 2 h (52.6 ± 20.8%ID/g) but sharply decreased at 24 and 48 h. Also, the liver showed similar uptake over time (range, 10-12%ID/g). On the contrary, 64Cu-PSMA I&T uptake of the tumors increased with time and peaked at 48 h (5.6 ± 0.1%ID/g). Conclusions: PSMA I&T labeled with 64Cu showed the feasibility of the PSMA specific PET imaging through in vitro and in vivo studies. Furthermore, 64Cu-PSMA I&T might be considered as the candidate of future clinical trial.

A Phase 0 Microdosing PET/CT Study Using O-[18F]Fluoromethyl-d-Tyrosine in Normal Human Brain and Brain Tumor.

PURPOSE: The aim of the present study was to obtain information about distribution, radiation dosimetry, toxicity, and pharmacokinetics of O-[18F]fluoromethyl-d-tyrosine (d-18F-FMT), an amino acid PET tracer, in patients with brain tumors. PATIENTS AND METHODS: A total of 6 healthy controls (age = 19-25 years, 3 males and 3 females) with brain PET images and radiation dosimetry and 12 patients (median age = 60 years, 6 males and 6 females) with primary (n = 5) or metastatic brain tumor (n = 7) were enrolled. We acquired 60-minute dynamic brain PET images after injecting 370 MBq of d-18F-FMT. Time-activity curves of d-18F-FMT uptake in normal brain versus brain tumors and tumor-to-background ratio were analyzed for each PET data set. RESULTS: Normal cerebral uptake of d-18F-FMT decreased from 0 to 5 minutes after injection, but gradually increased from 10 to 60 minutes. Tumoral uptake of d-18F-FMT reached a peak before 30 minutes. Tumor-to-background ratio peaked at less than 15 minutes for 8 patients and more than 15 minutes for 4 patients. The mean effective dose was calculated to be 13.2 µSv/MBq. CONCLUSIONS: Using d-18F-FMT as a PET radiotracer is safe. It can distinguish brain tumor from surrounding normal brain tissues with a high contrast. Early-time PET images of brain tumors should be acquired because the tumor-to-background ratio tended to reach a peak within 15 minutes after injection.

A preliminary clinical trial to evaluate 64Cu-NOTA-Trastuzumab as a positron emission tomography imaging agent in patients with breast cancer.

BACKGROUND: The purpose of this study was to evaluate both the biodistribution and safety of 64Cu-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-Trastuzumab, a novel 64Cu-labeled positron emission tomography (PET) tracer for human epidermal growth factor receptor 2 (HER2) in patients with breast cancer. METHODS: PET images at 1, 24, and 48 h after 296 MBq of 64Cu-NOTA-Trastuzumab injection were obtained from seven patients with breast cancer. Both the primary tumors' and metastatic lesions' maximum standardized uptake value (SUVmax) was evaluated. The mean SUVmax (SUVmean) was evaluated in the other organs, including the blood pool, liver, kidney, muscle, spleen, bladder, and the lungs, as well as the bones. Moreover, the internal radiation dosimetry was calculated using the OLINDA/EXM software. Safety was assessed based on feedback regarding adverse reactions and safety-related issues within 1 month after 64Cu-NOTA-Trastuzumab administration. RESULTS: 64Cu-NOTA-Trastuzumab PET images showed that the overall SUVmean values in each organ negatively correlated with time. The liver's average SUVmean values were measured at 5.3 ± 0.7, 4.8 ± 0.6, and 4.4 ± 0.5 on 1 h, 24 h, and 48 h after injection, respectively. The average SUVmean blood values were measured at 13.1 ± 0.9, 9.1 ± 1.2, and 7.1 ± 1.9 on 1 h, 24 h, and 48 h after injection, respectively. The SUVmax of HER2-positive tumors was relatively higher than HER2-negative tumors (8.6 ± 5.1 and 5.2 ± 2.8 on 48 h after injection, respectively). Tumor-to-background ratios were higher in the HER2-positive tumors than in the HER2-negative tumors. No adverse events related to 64Cu-NOTA-Trastuzumab were reported. The calculated effective dose with a 296 MBq injection of 64Cu-NOTA-Trastuzumab was 2.96 mSv. The highest absorbed dose was observed in the liver (0.076 mGy/MBq), followed by the spleen (0.063 mGy/MBq), kidney (0.044 mGy/MBq), and heart wall (0.044 mGy/MBq). CONCLUSIONS: 64Cu-NOTA-Trastuzumab showed a specific uptake at the HER2-expressing tumors, thus making it a feasible and safe monitoring tool of HER2 tumor status in patients with breast cancer. TRIAL REGISTRATION: CRIS, KCT0002790. Registered 02 February 2018, https://cris.nih.go.kr.

A microdose clinical trial to evaluate [18F]Florastamin as a positron emission tomography imaging agent in patients with prostate cancer.

PURPOSE: To evaluate the biodistribution of [18F]Florastamin, a novel 18F-labelled positron emission tomography (PET) tracer for prostate-specific membrane antigen (PSMA) for the diagnosis of prostate cancer. METHODS: PET was performed for five healthy controls and 10 patients with prostate cancer at 0, 10, 30, 70, and 120 mins after injecting 370 MBq of [18F]Florastamin. The maximum standardised uptake value (SUVmax) was evaluated in the primary tumour. The mean SUVmax (SUVmean) was evaluated in normal organs. Furthermore, the residence time was evaluated by assessing radioactivity in each organ. The internal radiation dosimetry was calculated using the OLINDA/EXM software. RESULTS: The SUVmax in primary tumours increased with time. A favourable tumour to background ratio was also observed over time. Multiple lymph nodes and bone metastases were also evaluated and showed a similar pattern to SUVmax in the primary tumour. In one patient, a tiny lymph node metastasis was identified using [18F]Florastamin PET, which was not observed using other modalities, and was histologically confirmed. The highest absorbed dose was observed in the kidney (0.062 ± 0.015 mGy/MBq), followed by the bladder (0.032 ± 0.013 mGy/MBq), liver (0.022 ± 0.006 mGy/MBq), and salivary gland (0.018 ± 0.006 mGy/MBq). The effective dose with a 370 MBq injection of [18F]Florastamin was 1.81 mSv. No adverse events related to [18F]Florastamin were reported. CONCLUSION: We identified a novel PSMA-targeted PET ligand, [18F]Florastamin, for imaging prostate cancer. [18F]Florastamin showed a high SUVmax and relatively high tumour to background ratio in both primary tumour and metastatic lesions, which suggests its high sensitivity to detect tumours without any adverse events. TRIAL REGISTRATION: KCT0003924 registered at https://cris.nih.go.kr/ .

Early prediction of neoadjuvant chemotherapy response for advanced breast cancer using PET/MRI image deep learning.

This study aimed to investigate the predictive efficacy of positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) for the pathological response of advanced breast cancer to neoadjuvant chemotherapy (NAC). The breast PET/MRI image deep learning model was introduced and compared with the conventional methods. PET/CT and MRI parameters were evaluated before and after the first NAC cycle in patients with advanced breast cancer [n = 56; all women; median age, 49 (range 26-66) years]. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were obtained with the corresponding baseline values (SUV0, MTV0, and TLG0, respectively) and interim PET images (SUV1, MTV1, and TLG1, respectively). Mean apparent diffusion coefficients were obtained from baseline and interim diffusion MR images (ADC0 and ADC1, respectively). The differences between the baseline and interim parameters were measured (ΔSUV, ΔMTV, ΔTLG, and ΔADC). Subgroup analysis was performed for the HER2-negative and triple-negative groups. Datasets for convolutional neural network (CNN), assigned as training (80%) and test datasets (20%), were cropped from the baseline (PET0, MRI0) and interim (PET1, MRI1) images. Histopathologic responses were assessed using the Miller and Payne system, after three cycles of chemotherapy. Receiver operating characteristic curve analysis was used to assess the performance of the differentiating responders and non-responders. There were six responders (11%) and 50 non-responders (89%). The area under the curve (AUC) was the highest for ΔSUV at 0.805 (95% CI 0.677-0.899). The AUC was the highest for ΔSUV at 0.879 (95% CI 0.722-0.965) for the HER2-negative subtype. AUC improved following CNN application (SUV0:PET0 = 0.652:0.886, SUV1:PET1 = 0.687:0.980, and ADC1:MRI1 = 0.537:0.701), except for ADC0 (ADC0:MRI0 = 0.703:0.602). PET/MRI image deep learning model can predict pathological responses to NAC in patients with advanced breast cancer.

Early response monitoring of neoadjuvant chemotherapy using [18F]FDG PET can predict the clinical outcome of extremity osteosarcoma.

BACKGROUND: To propose a personalized therapeutic approach in osteosarcoma treatment, we assessed whether sequential [18F]FDG PET/CT (PET/CT) could predict the outcome of patients with osteosarcoma of the extremities after one cycle and two cycles of neoadjuvant chemotherapy. METHODS: A total of 73 patients with AJCC stage II extremity osteosarcoma treated with 2 cycles of neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy were retrospectively analyzed in this study. All patients underwent PET/CT before (PET0), after 1 cycle (PET1), and after the completion of neoadjuvant chemotherapy (PET2), respectively. Maximum standardized uptake value (SUVmax) (corrected for body weight) and the % changes of SUVmax were calculated, and histological responses were evaluated after surgery. Receiver-operating characteristic (ROC) curve analyses and the Cox proportional hazards models were used to analyze whether imaging and clinicopathologic parameters could predict event-free survival (EFS). RESULTS: A total of 36 patients (49.3%) exhibited a poor histologic response and 17 patients (23.3%) showed events (metastasis in 15 and local recurrence in 2). SUVmax on PET2 (SUV2), the percentage change of SUVmax between PET0 and PET1 (Δ%SUV01), and between PET0 and PET2 (Δ%SUV02) most accurately predicted events using the ROC curve analysis. SUV2 (relative risk, 8.86; 95% CI, 2.25-34.93), Δ%SUV01 (relative risk, 5.97; 95% CI, 1.47-24.25), and Δ%SUV02 (relative risk, 6.00; 95% CI, 1.16-30.91) were independent predicting factors for EFS with multivariate analysis. Patients with SUV2 over 5.9 or Δ%SUV01 over - 39.8% or Δ%SUV02 over - 54.1% showed worse EFS rates than others (p < 0.05). CONCLUSIONS: PET evaluation after 1 cycle of presurgical chemotherapy can predict the clinical outcome of extremity osteosarcoma. [18F]FDG PET, which shows a potential role in the early evaluation of the modification of timing of local control, can be a useful modality for early response monitoring of neoadjuvant chemotherapy.

Comparisons of 131I-rituximab treatment responses in patients with aggressive lymphoma and indolent lymphoma.

OBJECTIVE: We evaluated the changes in treatment response over time after single 131I-rituximab radioimmunotherapy (RIT) according to non-Hodgkin lymphoma (NHL) types. METHODS: Fifteen aggressive and 21 indolent lymphoma cases undergoing RIT were evaluated. All patients underwent 18F-FDG-PET-CT before and 5 days, 1, and 3 months after RIT. The maximum standardized uptake value (SUV) and the sum of the products of the longest perpendicular diameters of tumours (SPD) were evaluated. Treatment responses were evaluated 1 and 3 months after RIT RESULTS: In aggressive lymphoma, SUV decreased at 5 days after RIT but increased after that. SPD decreased at 1 month but significantly increased at 3 months. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) at 1 month after RIT were changed to PD at 3 months after RIT. In indolent lymphoma, the SUV decreased continuously until 1 month after RIT. The SPD significantly decreased at 1 month and tended to further decrease to 3 months. CR, PR, SD, and PD at 1 month after RIT were achieved in 0, 8, 13, and 0 cases, respectively. Among the 13 SD cases, one changed to CR, three changed to PR, and nine had not changed at 3 months after RIT. CONCLUSIONS: The treatment response to single RIT differed depending on NHL type. These findings suggest a need to establish an optimal treatment regimen based on NHL aggressiveness.

An enhanced treatment effect can be expected from a higher serum thyroglobulin level after radioactive iodine therapy.

OBJECTIVE: The aim of this study was to investigate if increased serum thyroglobulin (Tg) levels after radioactive iodine (RAI) showed more therapeutic effects in patients with differentiated thyroid cancer (DTC). METHODS: Data of 65 patients with DTC who underwent RAI from June 2014 to September 2016 were reviewed. Serum thyroglobulin was measured immediately before (Tg1) and 48 h (Tg2) after RAI under TSH stimulation. Differences and ratios between serum Tg measurements (DeltaTg = Tg2 - Tg1 and RatioTg = Tg2/Tg1) were calculated. The treatment response of distant metastasis was assessed using the RECIST criteria. RESULTS: There was no difference in the median values of Tg1 and Tg2 (2.6 [range, 0.7-1957.5] ng/mL vs. 7.4 [range, 0.7-5276.0] ng/mL, p = 0.240) in all patients (73 scans, 65 patients). In subgroup analysis, Tg levels increased slightly in patients with distant metastasis (8 scans, 7 patients) (Tg1 vs. Tg2; 48.9 [range, 2.4-1957.5] ng/mL vs. 63.2 [range, 4.4-5276.0] ng/mL, p = 0.408). Among patients with distant metastasis, one patient with a partial response to treatment had a more than 4000fold increase in Tg levels and one patient with stable disease showed a 20fold increase in Tg levels. In contrast, five patients with disease progression showed only two to eightfold increase or more than 100fold decrease in Tg levels at 48 h after RAI. However, there was a significant increase in serum Tg levels in patients without distant metastasis (65 scans, 58 patients) after RAI (Tg1 vs. Tg2; 2.0 [range, 0.7-141.9] ng/mL vs. 6.8 [range, 0.7-577.7] ng/mL, p = 0.026). CONCLUSIONS: A higher elevation of Tg levels after RAI may be associated with a better treatment outcome in DTC patients with distant metastasis. An increase in Tg levels after RAI may reflect the destruction of cancer and thyroid cells.

Prediction of tumor differentiation using sequential PET/CT and MRI in patients with breast cancer.

OBJECTIVE: The aim of this study is to assess tumor differentiation using parameters from sequential positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) in patients with breast cancer. METHODS: This retrospective study included 78 patients with breast cancer. All patients underwent sequential PET/CT and MRI. For fluorodeoxyglucose (FDG)-PET image analysis, the maximum standardized uptake value (SUVmax) of FDG was assessed at both 1 and 2 h and metabolic tumor volume (MTV) and total lesion glycolysis (TLG). The kinetic analysis of dynamic contrast-enhanced MRI parameters was performed using dynamic enhancement curves. We assessed diffusion-weighted imaging (DWI)-MRI parameters regarding apparent diffusion coefficient (ADC) values. Histologic grades 1 and 2 were classified as low-grade, and grade 3 as high-grade tumor. RESULTS: Forty-five lesions of 78 patients were classified as histologic grade 3, while 26 and 7 lesions were grade 2 and grade 1, respectively. Patients with high-grade tumors showed significantly lower ADC-mean values than patients with low-grade tumors (0.99 ± 0.19 vs.1.12 ± 0.32, p = 0.007). With respect to SUVmax1, MTV2.5, and TLG2.5, patients with high-grade tumors showed higher values than patients with low-grade tumors: SUVmax1 (7.92 ± 4.5 vs.6.19 ± 3.05, p = 0.099), MTV2.5 (7.90 ± 9.32 vs.4.38 ± 5.10, p = 0.095), and TLG2.5 (40.83 ± 59.17 vs.19.66 ± 26.08, p = 0.082). However, other parameters did not reveal significant differences between low-grade and high-grade malignancies. In receiver-operating characteristic (ROC) curve analysis, ADC-mean values showed the highest area under the curve of 0.681 (95%CI 0.566-0.782) for assessing high-grade malignancy. CONCLUSIONS: Lower ADC-mean values may predict the poor differentiation of breast cancer among diverse PET-MRI functional parameters.

The Predictive Values of Lesion Size, F-18 FDG Avidity and I-131 Avidity for the Clinical Outcome of I-131 Treatment in Patients with Metastatic Differentiated Thyroid Carcinoma Only in the Lung.

PURPOSE: We aimed to evaluate the prognostic values of radiography, F-18 FDG PET, and I-131 whole body scans in patients with lung-only metastasis from differentiated thyroid carcinoma (DTC). METHODS: Between 1998 and 2013, we included 31 patients (F: 26, M: 5) with lung-only metastasis from DTC who had been treated with I-131 and underwent PET. Lung metastasis was categorized according to the size (macronodular ≥1.0 cm vs. micronodular <1.0 cm), FDG avidity (avid vs. non-avid), and I-131 avidity (avid vs. non-avid). Progression-free survival (PFS) was evaluated for each patient. RESULTS: Among 31 patients, seven (23%) had macronodular lung metastasis, 26 (84%) had FDG avid lung metastasis, and 16 (52%) had I-131 avid lung metastasis. During the median follow-up period of 9.4 y, median PFS was 6.1 y. Based on Kaplan-Meier analysis, macronodular lung metastasis (p = 0.017) and I-131 non-avid lung metastasis (p = 0.059) were significantly associated with worse outcomes, but FDG avid lung metastasis was not (p = 0.135). Patients with FDG non-avid lung metastasis did not experience disease progression during follow-up, while 11 of 26 patients (42%) experienced disease progression. Based on univariate analysis, the hazard ratio for a poor prognosis was 3.78 (p = 0.029) for macronodular lung metastasis and 3.29 (p = 0.079) for I-131 non-avid lung metastasis. CONCLUSIONS: Macronodular and I-131 non-avid lung metastasis were associated with a poor prognosis in lung-only metastasis from DTC. Although FDG avid lung metastasis may be associated with a poor prognosis, a larger-scale study is needed.

Radioimmunotherapy with (131)I-rituximab as consolidation therapy for patients with diffuse large B-cell lymphoma.

PURPOSE: The aim of this study was to assess the clinical activity and toxicity of (131)I-rituximab as consolidation therapy for patients with diffuse large B-cell lymphoma (DLBCL) who were treated with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone). METHODS: Patients who had been diagnosed with advanced stage (Ann Arbor III or IV) or bulky stage II DLBCL and achieved complete or partial response after six to eight cycles of R-CHOP were enrolled. RESULTS: A total of 16 patients were enrolled and treated with a single dose of (131)I-rituximab as consolidation therapy after the completion of six or eight cycles of R-CHOP between December 2005 and June 2011. This trial was terminated before the scheduled enrollment owing to low recruitment. Among the 16 patients who were treated with consolidative (131)I-rituximab, 6 achieved complete response (CR) after three cycles of R-CHOP, and another 9 patients further achieved CR after the completion of six or eight cycles of R-CHOP. During the median follow-up period of 73 months, only four patients (25 %) experienced relapse. Two-year relapse-free survival was 88 %, and 5-year relapse-free survival was 81 %. Grade 3 or 4 treatment-related toxicity occurred in four patients and included neutropenia and thrombocytopenia. CONCLUSIONS: (131)I-rituximab showed promising efficacy as consolidation treatment for patients with DLBCL. A future randomized phase III study to confirm our results is warranted.

Prognostic value of SUVmax measured by pretreatment 18F-FDG PET/CT in patients with primary gastric lymphoma.

PURPOSE: The aim of this retrospective study was to determine whether glucose metabolism assessed by fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) provides prognostic information independent of established prognostic factors in patients with gastric lymphoma. PATIENTS AND METHODS: We reviewed the medical records of 86 patients retrospectively (men, 42; women, 44; mean age 58±13 years) with pathologically proven gastric lymphoma (34 mucosa-associated lymphoid tissue and 52 aggressive non-Hodgkin's lymphoma). They underwent F-FDG PET/CT as part of a pretreatment work-up from February 2004 to July 2012. For the analysis, patients were classified by age, sex, Musshoff stage, serum lactate dehydrogenase, International Prognostic Index score, extragastric spread, and visual intensity [visual assessment and maximum standardized uptake value (SUVmax), respectively]. The relationship between F-FDG uptake and survival was analyzed using the Kaplan-Meier method with a log-rank test and Cox's proportional-hazard regression method. RESULTS: The median survival of all 86 study participants was 1117 days and the median SUV measured by PET/CT was 6.1 (range, 1.9-32.7). Patients with an SUVmax less than or equal to 5.2 survived significantly longer than patients with an SUVmax more than 5.2 (median, 1163 vs. 1004 days; P=0.003). Survival was also found to be significantly related to age (P=0.0005), histological type (P=0.004), extragastric spread (P=0.0004), International Prognostic Index score (P<0.0001), serum lactate dehydrogenase (P=0.02), stage (P<0.0001), and visual intensity (P=0.041). A multivariate analysis showed that patients with a higher SUVmax [P=0.021; 95% confidence interval (CI), 1.52-8.14; hazard ratio (HR)=6.29], older age (P=0.001; 95% CI, 4.64-219.96; HR=18.8), more aggressive histologic type (P=0.006; 95% CI, 2.20-70.63; HR=12.76), and higher stage (P=0.0006; 95% CI, 5.81-206.43; HR=17.48) showed worse survival. CONCLUSION: A higher SUVmax on pretreatment F-FDG PET/CT can predict poorer survival in patients with gastric lymphoma.

The Relationship Between Estrogen Receptor, Progesterone Receptor and Human Epidermal Growth Factor Receptor 2 Expression of Breast Cancer and the Retention Index in Dual Phase (18)F-FDG PET/CT.

PURPOSE: This study investigates the correlation of retention index (RI) using the dual phase FDG PET/CT scan with the breast cancer biomarkers. METHODS: A total of 55 patients with breast cancer underwent dual phase FDG PET/CT scans (60 and 120 min after FDG injection) before treatment. SUVmax and SUVmean of the primary breast tumors were measured, then the percent change of SUVmax and SUVmean between the two scans were calculated, and denoted as RImax and RImean, respectively. After the surgical resection of the breast tumor, the status of biomarkers (ER, PR, and HER-2) was evaluated in the postsurgical specimen. RESULTS: RImean was significantly higher in ER (-) (median, 16.2; IQR, 10.8-21.0) or HER-2 (+) (median, 16.1; IQR, 10.7-21.6) tumors than in ER (+) tumors (median, 9.9; IQR, 5.5-15.3) or HER-2 (-) tumors (median, 10.5; IQR, 5.5-16.1). However, there were no significant differences of SUVmax or RImax according to the ER or HER-2 status. There were no significant differences of any PET parameters between PR (+) and PR (-) tumors. Based off ROC curve analyses, RImean predicted the ER (+) tumors (AUC, 0.699; p = 0.006), and HER-2 (+) tumors (AUC, 0.674; p = 0.022), but not the PR (+) tumors. However, neither SUVmax nor RImax predicted ER (+), PR (+), or HER-2 (+) tumors. CONCLUSIONS: Retention index of SUVmean can reflect the ER and HER-2 status of breast cancers. Higher retention index of SUVmean might associate with lower ER expression and higher HER-2 expression.

Prognostic Value of SUVmax Measured by Pretreatment Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Patients with Ewing Sarcoma.

AIM: The aim of this retrospective study was to determine whether glucose metabolism assessed by using Fluorine-18 (F-18) fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) provides prognostic information independent of established prognostic factors in patients with Ewing sarcoma. METHODS: We retrospectively reviewed the medical records of 34 patients (men, 19; women, 15; mean age, 14.5 ± 9.7 years) with pathologically proven Ewing sarcoma. They had undergone F-18 FDG PET/CT as part of a pretreatment workup between September 2006 and April 2012. In this analysis, patients were classified by age, sex, initial location, size, and maximum standardized uptake value (SUVmax). The relationship between FDG uptake and survival was analyzed using the Kaplan-Meier method with the log-rank test and Cox's proportional hazards regression model. RESULTS: The median survival time for all 34 subjects was 999 days and the median SUV by using PET/CT was 5.8 (range, 2-18.1). Patients with a SUVmax ≤ 5.8 survived significantly longer than those with a SUVmax > 5.8 (median survival time, 1265 vs. 656 days; p = 0.002). Survival was also found to be significantly related to age (p = 0.024), size (p = 0.03), and initial tumor location (p = 0.036). Multivariate analysis revealed that a higher SUVmax (p = 0.003; confidence interval [CI], 3.63-508.26; hazard ratio [HR], 42.98), older age (p = 0.023; CI, 1.34-54.80; HR, 8.59), and higher stage (p = 0.03; CI, 1.21-43.95; HR, 7.3) were associated with worse overall survival. CONCLUSIONS: SUVmax measured by pretreatment F-18-FDG PET/CT can predict overall survival in patients with Ewing sarcoma.

The Role of (18)F-FDG PET/CT as a Prognostic Factor in Patients with Synovial Sarcoma.

PURPOSE: This research aims to investigate the potential of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET) to predict pathologic response after neoadjuvant chemotherapy (NAC) and overall survival (OS) of patients with synovial sarcoma in Korea. METHODS: Twenty patients with synovial sarcoma from January 2001 to December 2011 were reviewed retrospectively. All patients underwent pre-treatment FDG PET and tumor removal. Patients were classified with the maximum SUV (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), age, sex, histologic subtype, tumor size, NAC, resection margin, and metastasis at diagnosis. Pathologic response was assessed using the French Federation of Cancer Centers system. Statistical analyses were analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards regression model, and Mann-Whitney test. RESULTS: Nine patients (45 %) showed pathologic response, and ten patients survived. Higher SUVmax, higher MTV, higher TLG, monophasic epithelial type, and metastasis at diagnosis were significantly related to poorer OS (p = 0.047, 0.016, 0.016, 0.045, and 0.018, respectively). By multivariate analysis, metastasis at diagnosis was significantly related to poorer OS (p = 0.012/HR = 5.9, 95 % CI 1.47 to 24.1). The SUVmax, MTV, and TLG of the non-responder group were significantly higher than those of the responder group (p = 0.020, 0.020, and 0.020, respectively). There was no significant difference in size between the two groups (p = 0.062). CONCLUSIONS: A higher SUVmax on the pre-treatment scan, monophasic epithelial type, and metastasis at diagnosis were significantly associated with a poorer OS, and pathologic responders showed a higher SUVmax before NAC. The PET parameters can be used to predict OS and pathologic response in patients with synovial sarcomas before NAC.

Perirenal (18)F-FDG Uptake in a Patient with a Pheochromocytoma.

Increased (18)F-fluorodeoxyglucose (FDG) uptake of brown fat on (18)F-FDG positron emission tomography (PET) originating from physiological activation is a common incidental finding and is usually located in the neck, shoulder, and supraclavicular areas. We present a case of an incidental pheochromocytoma showing diffusely increased (18)F-FDG uptake in bilateral perirenal fat tissue as well as supraclavicular and paravertebral fat tissue on (18)F-FDG PET/CT. The patient had no clinical symptoms except hypertension, and a pheochromocytoma was confirmed in a postsurgical specimen. A pheochromocytoma should be considered a cause in cases of increased (18)F-FDG uptake of perirenal brown fat.