PET and restaging of malignant lymphoma including residual masses and relapse

Differentiation of post-therapeutic scar tissue from active lymphoma is unsatisfactory when using only morphological imaging approaches. Positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) may provide superior clinical information by enabling biochemical tissue characterisation, with enhanced FDG uptake in viable post-therapeutic lymphoma masses and very low uptake in indolent fibrotic tissue. With this in mind, 15 recently published studies reporting the results of differentiation of viable lymphoma from scar tissue in 723 patients were analysed. Sensitivity of FDG-PET for detection of active disease was 71–100%, and the specificity was 69–100%. Accordingly, FDG-PET had a high negative predictive value of 80–100%. In contrast, the specificity and positive predictive value (PPV) of computed tomography were low (4–31% and 19–60%, respectively, except in one study in which the PPV was 82%). Residual masses that were positive on PET were associated with a progression-free survival of 0–40%. Although not perfect, the biochemical approach for characterisation of residual masses in lymphoma with FDG-PET at present seems the most accurate way to differentiate scar tissue from viable residual lymphoma.

     

PET and restaging of malignant lymphoma including residual masses and relapse

Differentiation of post-therapeutic scar tissue from active lymphoma is unsatisfactory when using only morphological imaging approaches. Positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose (FDG) may provide superior clinical information by enabling biochemical tissue characterisation, with enhanced FDG uptake in viable post-therapeutic lymphoma masses and very low uptake in indolent fibrotic tissue. With this in mind, 15 recently published studies reporting the results of differentiation of viable lymphoma from scar tissue in 723 patients were analysed. Sensitivity of FDG-PET for detection of active disease was 71-100%, and the specificity was 69-100%. Accordingly, FDG-PET had a high negative predictive value of 80-100%. In contrast, the specificity and positive predictive value (PPV) of computed tomography were low (4-31% and 19-60%, respectively, except in one study in which the PPV was 82%). Residual masses that were positive on PET were associated with a progression-free survival of 0-40%. Although not perfect, the biochemical approach for characterisation of residual masses in lymphoma with FDG-PET at present seems the most accurate way to differentiate scar tissue from viable residual lymphoma.     

FDG-PET for predicting the prognosis of malignant lymphoma

To evaluate the usefulness of FDG-PET as a predictor of prognosis, 34 patients with untreated malignant lymphoma in the head and neck region were studied. After FDG-PET and treatment, they were observed from 15 to 50 months. Tumors which were aggressive and resistant to treatment tended to show high uptake of FDG. The survival rate of patients with high uptake of FDG, DAR > 8, was lower than the rate of the other patients. It is considered to be useful to add FDG uptake of the tumor to other prognostic factors for predicting the prognosis.     

全身扩散加权成像在恶性淋巴瘤诊断中的价值

目的：评价全身磁共振扩散加权成像（WB-DWI）在恶性淋巴瘤诊断及疗效评价中的作用。方法：回顾性分析47例经病理证实的恶性淋巴瘤患者WB-DWI表现;另选10例健康志愿者进行比较。8例霍奇金淋巴瘤（HD）患者,其中5例治疗前、后均行WB-DWI检查,3例为治疗后患者;39例非霍奇金淋巴瘤（NHL）患者,治疗前行WB-DWI检查19例,治疗前、后均行WB-DWI检查11例,仅治疗后检查9例。在ADC图上分别测量恶性淋巴瘤患者和健康志愿者淋巴结的ADC值,16例复查患者在初次检查相一致部位再次测量淋巴结的ADC值,并进行前后比较,同时与健康志愿者进行比较。结果：全身MR-DWI对淋巴瘤的显示较敏感,MR-DWI共检出大于1cm淋巴结372处。35例治疗前恶性淋巴瘤患者平均ADC值为（0.86±0.21）×10^-3mm^2/s,28例治疗后复查患者平均ADC值为（1.22±0.31）×10^-3mm^2/s,治疗前、后平均ADC值的差异具有统计学意义（P〈0.05）;10例健康志愿者颈部淋巴结平均ADC值为（1.29±0.12）×10^-3mm^2/s,与30例治疗前淋巴瘤患者ADC值比较,差异具有统计学意义,与28例治疗后患者ADC值比较,差异无统计学意义（P〉0.05）。结论：WB-DWI和ADC值的测量在恶性淋巴瘤的临床诊断、分期及疗效监测的评价方面是一种快速和行之有效的技术,具有一定的临床价值。     

Clinical impact of whole body FDG-PET on the staging and therapeutic decision making for malignant lymphoma

OBJECTIVES: The aim of this study is to evaluate the clinical impact of whole-body FDG-PET for the pre-therapeutic evaluation of malignant lymphoma and compared to that of 67Ga-scintigraphy when added to non-RI examinations. METHODS: We examined 46 patients with malignant lymphoma including 42 newly diagnosed cases and 4 relapsed cases. Whole-body FDG-PET was started 63 minutes after the administration of FDG with ECAT EXACT HR+. The clinical stage of each patient was determined based on the results of a non-RI examination (consisting of physical examination, CT, gastrointestinal studies and bone marrow aspiration), 67Ga planar images and FDG-PET. Discrepant findings were verified based on the response to treatment and the findings of a follow-up examination more than 6 months after treatment. Finally, 152 nodal regions and 19 extranodal tissues were found to be involved by disease. RESULTS: In the 152 nodal lesions, FDG-PET detected 54 nodal lesions in addition to 98 lesions detected by non-RI examinations, whereas 67Ga-scintigraphy detected 14 additional lesions. The sensitivity of non-RI, non-RI + 67Ga and non-RI + FDG was 64.5%, 73.7% and 100.0%, respectively. In 19 extranodal lesions, FDG-PET detected 5 extranodal lesions in addition to 13 lesions detected by non-RI examinations, whereas 67Ga-scintigraphy detected 1 additional lesion. The sensitivity of non-RI, non-RI + 67Ga and non-RI + FDG was 68.4%, 73.7% and 94.7%, respectively. When combining the FDG-PET findings with the non-RI findings, the improvement of the detectability was much higher than that when 67Ga findings were combined to the non-RI findings. For the staging of lymphoma, the non-RI and non-RI + 67Ga findings accurately diagnosed 76.1% and 80.4%, respectively, whereas the non-RI + FDG findings accurately diagnosed 82.6%. Finally, FDG-PET resulted in changes in the clinical management of 8 patients (17.4%). CONCLUSIONS: FDG-PET offers more information in addition to the findings of conventional diagnostic methods than 67Ga-scintigraphy in order to accurately detect malignant lymphoma. FDG-PET can therefore play an important role in therapeutic decision making on lymphoma.     

FDG-PET on the day after first chemotherapy in malignant lymphoma

Positron emission tomography using 18F-fluorodeoxyglucose (FDG-PE) was performed in four patients with non-Hodgkin's lymphoma on the day after initial chemotherapy, in an attempt to predict the effects of chemotherapy earlier than standard methods. Twelve regions displaying intense uptake on baseline FDG-PET were selected, and decreases in the rate for each region were calculated from standardized uptake values on the day following chemotherapy. Seven of the 12 regions demonstrated decrease rates of 60% or more, and two decreased by 100%. This study indicates that FDG-PET on the day after first chemotherapy seems to reflect the effect of chemotherapy on malignant lymphoma.     

Prognostic value of FDG-PET in malignant lymphoma.

Lymphomas have represented an indication for nuclear medicine investigations for 30 years. Gallium-67 scintigraphy has been shown to be a valuable complementary method in Hodgkin's disease and non-Hodgkin lymphoma for detecting viable residual lesions after chemotherapy and for diagnosis of a relapse. Thallium-201 is of interest in differentiating cerebral lymphomas from infectious lesions in AIDS patients but less useful in extra-cerebral lymphomas. PET with fluorine-18-FDG is more accurate than 67Ga in lymphoma. In patients with a positive PET scan after chemotherapy an early relapse occurs in up to 100%, while more than 80% of patients with a negative PET will have a long-term remission. Most studies show that FDG-PET is significantly correlated with patient outcome whereas there is much weaker or even no correlation for CT. The main reason is that PET is not bound to morphological criteria like lymph node size while CT is often not able to differentiate between residual tumour and post-therapeutic fibrosis. Therefore, based on a considerable number of clinical studies, FDG-PET gains increasing significance for staging, restaging and therapy monitoring in malignant lymphomas.     

Detection of local residual tumor after laryngeal cancer treatment using FDG-PET

OBJECTIVE: Fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) is sometimes used as a means of follow-up after diagnosis and treatment of cancers of the head and neck region. The present study was undertaken to evaluate the ability of FDG-PET to detect local residual tumor after treatment of laryngeal cancer. METHODS: Thirty-six patients with laryngeal cancer underwent FDG-PET before and after initial treatment. Of these patients, 20 received FDG-PET before treatment and 28 received it after treatment. The relationship between standardized uptake values (SUV) and the presence or absence of local residual tumor was investigated by setting the cut-off value of the SUV using the receiver operating characteristics (ROC) curve. RESULTS: When the pre-treatment SUV threshold for laryngeal cancer was set at 7.20, the detection of local residual tumor after treatment using FDG-PET had a sensitivity of 77.78%, specificity of 81.82%, false positive rate of 18.18%, false negative rate of 22.22%, accuracy of 80% and a p value of 0.02. When the post-treatment SUV threshold for the larynx was set at 3.35, the test had a sensitivity of 93.75%, specificity of 91.67%, false positive rate of 8.33%, false negative rate of 6.25%, accuracy of 92.86% and a p value of 0.0001. CONCLUSIONS: FDG-PET was found to be useful for determining the presence of local residual tumor after treatment of laryngeal cancer.     

多发性骨软骨瘤病的99Tcm-MDP全身骨显像分析

目的 分析多发性骨软骨瘤病的99mTc-MDP全身骨显像的影像特点,评价骨显像在多发性骨软骨瘤病中的应用价值.方法 回顾分析62例确诊为多发性骨软骨瘤病患者的临床、骨显像及其他影像学资料,总结多发性骨软骨瘤病的骨显像特点,并与其他影像学结果进行比较.结果 62例患者中,100％在身体不同地方发现无痛性骨性包块,其中17.7％伴有关节功能障碍,53.2％有家族史.骨显像发现全身骨骼受累最多的部位前三位分别为胫骨近端17.4％、股骨远端17.0％、股骨近端16.4％.受累最少的部位为颅骨0％.在所有病灶中,1级摄取病灶占全部病灶的7.9％(24/305)、2级摄取病灶占全部病灶的34.1(104 /305)、3级摄取病灶占全部病灶的40.0％(122/305)、4级摄取病灶占全部病灶的18％(55/305).结论 多发性骨软骨瘤病的全身骨显像表现为长骨末端异常的、不规则的、多处的放射性浓聚,结合临床及其他影像学资料,99mTc-MDP全身骨显像可用于多发性骨软骨瘤病患者的诊断与鉴别诊断、随访以及肿瘤恶变的评价.     

Usefulness of FDG-PET imaging for the radiotherapy treatment planning of pyothorax-associated lymphoma

Pyothorax-associated lymphoma (PAL) is a non-Hodgkin's lymphoma developing in the pleural cavity after a long-standing history of chronic pyothorax (CP). F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging is a useful modality for determination of disease extent of various malignant tumors, including malignant lymphoma, but there have been no reports describing the usefulness of FDG-PET imaging in PAL. Here we report a case of PAL that relapsed after chemotherapy and was successfully treated by radiotherapy. FDG-PET imaging revealed that the tumor was localized to a soft-tissue attenuation mass behind the CP cavity in the right thorax, but did not infiltrate the CP cavity. A total dose of 40 Gy was administered to the area that included the PET-positive lesion, instead of including the entire CP cavity in the radiation field. Although computed tomography (CT) showed a residual mass, no FDG uptake was indicated by FDG-PET imaging performed just after the end of radiotherapy, and additional irradiation was not performed. No sign of relapse was found by FDG-PET imaging 3 months later. FDG-PET imaging was useful for both the planning of radiotherapy and assessing the treatment response of PAL.     

FDG-PET/CT in re-staging of patients with lymphoma

The aim of this study was to evaluate the clinical significance of combined fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography (FDG-PET/CT) in patients with lymphoma, and to compare the FDG-PET/CT staging results with those of FDG-PET and CT alone. Twenty-seven patients were studied. Each patient had clinical follow-up for >12 months and entered complete follow-up evaluation. Patient-based evaluation showed a sensitivity of 78% for CT alone, 86% for FDG-PET alone, 93% for CT and FDG-PET read side by side, and 93% for combined FDG-PET/CT imaging. Region-based evaluation showed a sensitivity for regional lymph node involvement of 61%, 78%, 91% and 96% respectively. FDG-PET/CT imaging is superior to CT alone (P=0.02) and has additional benefit over FDG-PET alone due to exact anatomical localisation. We conclude that FDG-PET/CT imaging is accurate in re-staging lymphoma and offers advantages over separate FDG-PET and CT imaging.     

Magnetic resonance in the study of residual mediastinal masses after therapy of lymphoma]

Forty-five patients with mediastinal spread of malignant, Hodgkin's and non-Hodgkin's lymphomas were examined with MR Imaging at 0.5 T. Ninety-two examinations were performed at diagnosis and/or during and after treatment to investigate MR capabilities in distinguishing fibrous tissue from active disease in the masses residuing after therapy--which cannot be done by means of CT. MR results indicated T2-weighted sequences to be the most useful. MR results were compared with the data collected from follow-up, clinics, and biology. MR Imaging had high accuracy (92.1%). The number of false negatives was very low, thanks to the low intensity of fibrous tissue, while a relatively high number of false positives was observed, probably due to the difficulties in discriminating inflammatory from neoplastic tissue.     

全身弥散加权成像在恶性肿瘤的应用研究进展

全身弥散加权成像（wholebody diffusion weighted imaging,WB-DWI）是一项全新的磁共振成像技术,在恶性肿瘤的诊断及鉴别诊断、分期及可切除性评估、预后及疗效监测等方面得到了初步应用,本文对WB-DWI临床应用的最新研究进展作一综述。     

SAPHO综合征25例99Tcm—MDP全身骨显像分析

目的分析滑膜炎、痤疮、脓疱病、骨肥厚、骨炎综合征（即SAPHO综合征）99Tcm．MDP全身骨显像的影像特点,评价骨显像在SAPHO综合征中的应用价值。方法回顾分析25例确诊为SAPHO综合征患者的临床、骨显像及其他影像学资料,将骨骼病变部位分为前胸壁（包括锁骨、胸骨以及胸锁关节、肋胸连接、胸骨柄体连接）、脊柱、下颌骨、骶髂关节以及四肢骨,总结SAPHO综合征骨显像特点,并与其他影像学结果进行比较。结果25例患者中,32％（8／25）合并有皮肤损害;48％（12／25）骨活组织检查证实为慢性非特异性炎性反应。骨显像发现全部患者均有前胸壁受累,胸肋锁骨关节和连接受累率为96％（24／25）,其中胸锁关节、第一肋胸连接以及胸骨柄体连接的受累率分别为60％（15／25）、48％（12／25）和44％（11／25）,但骨显像呈典型“牛头”征表现的患者仅有20％（5／25）;脊柱及四肢骨受累率分别为44％（11／25）和16％（4／25）。骨显像发现68％（17／25）患者有隐匿性病灶,主要分布在第一肋胸连接、胸锁关节、胸骨柄体连接和脊柱。结论胸肋锁骨关节和连接受累为SAPHO综合征的影像特点,结合临床及其他影像学资料,99Tcm--MDP全身骨显像可用于SAPHO综合征患者的诊断与鉴别诊断、发现隐匿病灶以及评价病灶活性。     

Assessment of the nature of residual masses at end of treatment in lymphoma patients using volume perfusion computed tomography

Objectives

To determine the diagnostic benefit of volume perfusion computed tomography (VPCT) at end of treatment for response assessment in lymphoma patients.

Methods

Seventy-five patients with different lymphoma subtypes were included: 50/75 patients had residual masses at end of treatment, 26/50 patients underwent VPCT at baseline and at end of treatment, and 24/50 patients only had end-of-treatment VPCTs. We evaluated the size of the main lymphoma mass, its blood flow (BF), blood volume (BV) and k-trans, calculated ratios (baseline and end of treatment) as well as sensitivity/specificity/negative (NPV)/positive predictive values (PPV). For VPCT at end of treatment, a cutoff threshold between responders and non-responders was calculated.

Results

For patients undergoing VPCT at baseline and end of treatment, reduction in size, BF, BV and k-trans was significant (P?<?0.001). Identification of non-response was reached at: <53 % reduction in size (sensitivity/specificity/accuracy/PPV/NPV of 88.89 %/62.5 %/80.77 %/84.21 %/71.43 %), <15 % reduction of BF (sensitivity/specificity/accuracy/PPV/NPV of 100 %/37.5 %/80.77 %/0.26 %/100 %), or <45 % reduction of k-trans (sensitivity/specificity/accuracy/PPV/NPV of 88.89 %/75 %/84.62 %/88.89 %/75 %). In the subgroup undergoing VPCT at end of treatment, BF >18.51 ml/100 ml indicated non-responsiveness (sensitivity 92.86 %, specificity 72.73 %, accuracy 84 %, PPV 81.25 %, NPV 88.89 %).

Conclusions

VPCT seems adequate for assessment of lymphoma response at end of treatment. The degree of residual lymphoma perfusion at end of treatment helps to identify patients likely to remain in remission 1 year after completion of therapy.

Key Points

? Volume perfusion computed tomography (VPCT) offers measurements for assessing tumour response. ? Perfusion parameter changes measured by VPCT correlate with antitumour therapy response. ? In lymphoma, baseline and end-of-treatment perfusion parameter ratios can predict response. ? Perfusion measurements after treatment identify patients likely to remain in remission.     

Pulmonary drug toxicity: FDG-PET findings in patients with lymphoma

Objective The objective of this study was to evaluate the prevalence and positron emission tomography (PET) imaging features of pulmonary drug toxicity in patients with lymphoma during or just following chemotherapy. Methods A total of 677 PET scans on 460 patients with lymphoma (351 non-Hodgkin’s lymphoma, 92 Hodgkin’s disease, and 17 both Hodgkin’s and non-Hodgkin’s lymphoma) were performed for the evaluation of chemotherapy response. In 51 patients, abnormal accumulation on both sides of the chest was reported. A review of medical records, ¹⁸fluorodeoxyglucose (¹⁸FDG)-PET scans, and chest computed tomography (CT) was performed, and cases with probable drug toxicity were identified. Inclusion criteria of probable drug toxicity were abnormal but symmetrical FDG accumulation in both lungs seen during or just following the completion of chemotherapy, the abnormal accumulation or corresponding abnormal CT findings resolved on sub sequent studies, exclusion of clinical diagnosis of pneumonia, radiation pneumonitis, or lymphoma involvement. Results In 10 patients (six men and four women, average age 47.3), 2.2% of cases, probable drug toxicity was identified. In all 10 cases, diffuse and subpleural-dominant FDG accumulation was seen on FDG-PET scans, and scattered or diffuse ground-glass opacities were observed on chest CT. Four patients reported symptoms, and six patients did not report any symptoms. Conclusions Diffuse and peripheral-dominant FDG accumulation in the lung, which may represent pulmonary drug toxicity, was not uncommon in patients with lymphoma who underwent chemotherapy. FDG-PET scan might be able to detect pulmonary drug toxicity in asymptomatic patients.     

Comparison of current density viability imaging at rest with FDG-PET in patients after myocardial infarction

The assessment of myocardial viability is a major diagnostic challenge in patients with coronary artery disease (CAD) after myocardial infarction. Novel threedimensional current density (CD) imaging algorithms use high-resolution magnetic field mapping to determine the electrical activity of myocardial segments at rest. We, for the first time, compared CD activity obtained with several algorithms to 18-F-fluoro-deoxyglucose positron emission tomography (FDG-PET) in evaluation of myocardial viability. Magnetic field maps were obtained in nine adult patients (pt) with CAD and a history of infarction. The criterion for non-viable myocardium was an FDG-PET uptake with less than 45% of the maximum in the respective segments. CD imaging was applied to the left ventricle by using six different methods to solve the inverse problem. Mean CD activity was calculated for a close meshed grid of 90 locations of the left ventricle. A cardiologist compared bull's eye plots of CD and FDG-PET activity by eye. Spearman's correlation coefficients and specificity at a given level of sensitivity (70%) were calculated. Bull's eye plots revealed a significant correlation of CD/PET in 5 pt and no correlation in 3 pt. One pt had a negative correlation. The six different CD reconstruction methods performed similar. While CD reconstruction has the principal potential to image viable myocardium, we found that the reconstructed CD magnitude was low in scar segments but also reduced in some segments with preserved metabolic activity under resting conditions. New vector measurement techniques, the use of additional stress testing and advances in mathematical methodology are expected to improve CD imaging in future.