Positron emission tomography computed tomography features of monomorphic epitheliotropic intestinal T-cell lymphoma

Objective: To define the positron emission tomography/computed tomography (PET/CT) features of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), a rare malignancy in European and North American populations and the most common form of primary intestinal T-cell lymphoma in Asian populations.

Methods: ¹⁸F-fluorodeoxyglucose (FDG) PET/CT findings of a cohort of MEITL patients were retrospectively analyzed.

Results: Eight men and four women with MEITL investigated by PET/CT at diagnosis and relapse were retrospectively analyzed. On presentation, the primary involved sites were the small bowel (N?=?8), large bowel (N?=?2), stomach (N?=?1) and small and large bowels (N?=?1). The uninvolved small bowel did not show increased FDG-avidity to suggest enteropathy. On presentation, lymph nodes and other organs were involved in seven cases (58%). The primary lesions were hypermetabolic except in one case, where the colonic lesion was eumetabolic. At relapse, the stomach and large bowel might be involved even if the primary tumours arose from the small bowel, and multiple extra-intestinal metastases occurred. Interestingly, thoracic structures and the brain were frequently involved (50% and 25% respectively).

Conclusion: These findings showed that in contrast to classical enteropathy-associated T-cell lymphoma, where the small bowel is the exclusive primary site (owing to its origin from coeliac disease) and distant metastases even during relapse are exceptional, MEITL might on presentation and during relapse involve any part of the gut, and metastasize to multiple extra-intestinal sites.     

Direct comparison of 18F-fluorodeoxyglucose coincidence gamma camera tomography with gallium scanning for the staging of lymphoma

BACKGROUND: The present study compared the performance of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) using a coincidence dual-head gamma camera (FDG Co-PET) with 67gallium scinti graphy (GS) in pretreatment staging of lymphoma. METHODS: A total of 46 patients underwent FDG Co-PET, computed tomography (CT) scanning and GS for pretreatment staging of lymphoma (40 newly diagnosed and recurrence) between November 1997 and December 1999. RESULTS: Histological subgroups comprised low grade (8 patients), intermediate grade (25) high-grade (3) non-Hodgkin's lymphoma and Hodgkin's disease (10). Based on clinical assessment, CT scan findings and biopsy, 100 nodal sites and 15 extra-nodal sites were deemed positive. FDG Co-PET was superior to GS in nodal site positivity rate (97%vs 79%, P < 0.0001). Compared with GS, FDG Co-PET detected 39 more abnormal sites in 22 patients (48%), of which 28 sites were validated by biopsy, CT and/or progress FDG Co-PET scanning. There was only one proven false negative FDG site in the spleen. CT + FDG Co-PET led to upstaging in 2 patients (4%), compared to CT + GS. CONCLUSION: FDG Co-PET shows potential for providing an accurate means for pretreatment staging of lymphoma and can detect extra sites of disease activity compared to GS.     

The prognostic value of interim positron emission tomography scan in patients with classical Hodgkin lymphoma

The prognostic value of interim positron emission tomography (PET) was evaluated after 2 cycles of doxorubicin, bleomycin, vinblastin and dacarbazine in classical Hodgkin lymphoma patients (n = 229), based on Deauville criteria. In early stage non‐bulky disease, bulky stage II disease, advanced stage low International Prognostic Score (IPS ≤2) and advanced stage (IPS ≥3), 3‐year progression‐free survival rates in PET2‐negative vs. PET2‐positive groups were 95·9% vs. 76·9% (P < 0·0018), 83·3% vs. 20·0% (P = 0·017), 77·0% vs. 30·0% (P < 0·001) and 71·0% vs. 44·4%(P = 0·155), respectively. The outcome after positive PET2 was better than previously reported. The results from non‐randomized studies of PET2‐guided therapy would be valuable with careful interpretation.     

Positron emission tomography derived metrics in relapsed or refractory large B-cell lymphoma with residual disease before autologous stem cell transplant

Salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) is a potentially curative treatment for patients with relapsed or refractory large B-cell lymphoma (rrLBCL) with chemosensitive disease. A¹⁸F-fluorodeoxyglucose positron emission tomography (PET) scan after salvage chemotherapy is used to assess response and eligibility for ASCT, but metrics for chemosensitivity in patients with residual disease are not well defined. We performed a single-centre retrospective analysis of 92 patients with a partial response or stable disease after salvage chemotherapy for rrLBCL who received ASCT to investigate PET-derived parameters and their prognostic utility. The Deauville 5-point Scale (D-5PS) score, maximum standardised uptake value (SUV_max), total metabolic tumour volume (TMTV), and total lesion glycolysis (TLG) were calculated from the post-salvage/pre-ASCT PET scan. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 40% and 54% respectively. A D-5PS score of 5 (p = 0.0082, hazard ratio [HR] 2.09), high SUV_max (p = 0.0015, HR 2.48), TMTV (p = 0.035, HR 1.83) and TLG (p = 0.0036, HR 2.27) were associated with inferior PFS. A D-5PS score of 5 (p = 0.030, HR 1.98) and high SUV_max (p = 0.0025, HR 2.55) were associated with inferior OS. PET-derived parameters may help prognosticate outcomes after ASCT in patients with rrLBCL with residual disease after salvage chemotherapy.     

Positron emission tomography/computed tomography surveillance in patients with Hodgkin lymphoma in first remission has a low positive predictive value and high costs

Background

The value of performing post-therapy routine surveillance imaging in patients with Hodgkin lymphoma is controversial. This study evaluates the utility of positron emission tomography/computed tomography using 2-[18F]fluoro-2-deoxyglucose for this purpose and in situations with suspected lymphoma relapse.

Design and Methods

We conducted a multicenter retrospective study. Patients with newly diagnosed Hodgkin lymphoma achieving at least a partial remission on first-line therapy were eligible if they received positron emission tomography/computed tomography surveillance during follow-up. Two types of imaging surveillance were analyzed: “routine” when patients showed no signs of relapse at referral to positron emission tomography/computed tomography, and “clinically indicated” when recurrence was suspected.

Results

A total of 211 routine and 88 clinically indicated positron emission tomography/computed tomography studies were performed in 161 patients. In ten of 22 patients with recurrence of Hodgkin lymphoma, routine imaging surveillance was the primary tool for the diagnosis of the relapse. Extranodal disease, interim positron emission tomography-positive lesions and positron emission tomography activity at response evaluation were all associated with a positron emission tomography/computed tomography-diagnosed preclinical relapse. The true positive rates of routine and clinically indicated imaging were 5% and 13%, respectively (P=0.02). The overall positive predictive value and negative predictive value of positron emission tomography/computed tomography were 28% and 100%, respectively. The estimated cost per routine imaging diagnosed relapse was US$ 50,778.

Conclusions

Negative positron emission tomography/computed tomography reliably rules out a relapse. The high false positive rate is, however, an important limitation and a confirmatory biopsy is mandatory for the diagnosis of a relapse. With no proven survival benefit for patients with a pre-clinically diagnosed relapse, the high costs and low positive predictive value make positron emission tomography/computed tomography unsuitable for routine surveillance of patients with Hodgkin lymphoma.     

Positron emission tomography/computerized tomography in the evaluation of primary non-Hodgkin’s lymphoma of prostate

Primary malignant lymphoma of the prostate is exceedingly rare.Here we report a case of a 65-year-old man who presented with increased urinary frequency,urinary urgency,and urinary incontinence for two years.Benign prostatic hypertrophy was suspected at primary impression.Ultrasound revealed a hypoechoic lesion of the prostate.The total serum prostate-specific antigen was within normal range.Positron emission tomography/computerized tomography(PET/CT)showed a hypermetabolic prostatic lesion.Prostate biopsy was consistent with a non-germinal center diffuse large B cell lymphoma.There was complete remission of the prostatic lesion following six cycles of chemotherapy as shown on the second PET/CT imaging.18F-fluoro-deoxy glucose PET/CT is not only a complement to conventional imaging,but also plays a significant role in the diagnosis and evaluation of treatment response of prostatic lymphoma.     

Disease staging with positron emission tomography or gallium scanning and use of rituximab predict outcome for patients with diffuse large B-cell lymphoma treated with autologous stem cell transplantation

Tumor status, as determined by positron emission tomography or gallium scanning (PET/G), may be an important predictor of outcome for patients with diffuse large B-cell lymphoma (DLBCL) undergoing autologous stem cell transplantation (ASCT). ASCT conditioning regimens that include rituximab may reduce the rate of relapse. We evaluated the influence of rituximab on overall and progression-free survival in patients with DLBCL based on PET/G status before ASCT. A retrospective review of all patients with chemosensitive DLBCL who underwent ASCT in the context of research protocols at our institution between 1995 and 2005 was performed. Our study included 174 patients. Disease status before ASCT, according to PET/G, was negative in 136 patients (78%), positive in 29 patients (17%), and unknown in nine patients (5%). PET/G status and rituximab use were the only factors predictive of progression-free survival in multivariate analyses: the hazard ratios for relapse were 2·9 for PET/G-positive versus -negative patients ( P  <   0·001) and 0·4 for rituximab versus no rituximab use ( P  =   0·001). We conclude that evidence of disease on PET/G scanning prior to transplantation is associated with an increased risk for relapse after ASCT. Transplantation regimens containing rituximab can reduce this risk, regardless of PET/G status.     

Positron emission tomography (PET) for cholangiocarcinoma

The combination of positron emission tomography (PET) with computed tomography (PET-CT) provides simultaneous metabolic and anatomic information on tumors in the same imaging session. Sensitivity of PET/PET-CT is higher for intrahepatic (>90%) than for extrahepatic cholangiocarcinoma (CCA) (about 60%). The detection rate of distant metastasis is 100%. PET, and particularly PET-CT, improves the results and impacts on the oncological management in CCA compared with other imaging modalities. Therefore, PET-CT is recommended in the preoperative staging of intrahepatic (strength of recommendation: moderate) and extrahepatic (strength of recommendation: low) CCA.     

Positron emission tomography: current status and future challenges

Positron emission tomography (PET) using fluorine-18–2-fluoro-2-deoxy- d -glucose (FDG) has made a major impact in clinical oncology in diagnosing, staging and restaging malignancy as well as in monitoring therapy response. Over the past decade, there has been an enormous growth in the scientific and clinical evidence supporting PET including recent important contribution from the Australian PET Data Collection Project. Since 2001, hybrid PET-computed tomography has also largely replaced PET alone systems with significant improvement in diagnostic accuracy. This review is a brief update on the current status of FDG-PET focusing on its oncologic applications.     

Diagnostic role of 18F-fluorodeoxyglucose positron emission tomography for follicular lymphoma with gastrointestinal involvement

AIM:To investigate the capacity for 18F-fluorodeoxyglucose(18F-FDG) positron emission tomography(PET) to evaluate patients with gastrointestinal lesions of follicular lymphoma.METHODS:This retrospective case series consisted of 41 patients with follicular lymphoma and gastrointestinal involvement who underwent 18F-FDG-PET and endoscopic evaluations at ten different institutions between November 1996 and October 2011.Data for endoscopic,radiological,and biological examinations performed were retrospectively reviewed from clinical records.A semi-quantitative analysis of 18F-FDG uptake was performed for each involved area by calculating the maximum standardized uptake value(SUVmax).Based on the positivity of 18F-FDG uptake in the gastrointestinal lesions analyzed,patients were subdivided into two groups.To identify potential predictive factors for 18F-FDG positivity,these two groups were compared with respect to gender,age at diagnosis of lymphoma,histopathological grade,pattern of follicular dendritic cells,mitotic rate,clinical stage,soluble interleukin-2 receptor levels detected by 18F-FDG-PET,lactate dehydrogenase(LDH) levels,hemoglobin levels,bone marrow involvement,detectability of gastrointestinal lesions by computed tomography(CT) scanning,and follicular lymphoma international prognostic index(FLIPI) risk.RESULTS:Involvement of follicular lymphoma in the stomach,duodenum,jejunum,ileum,cecum,colon,and rectum was identified in 1,34,6,3,2,3,and 6 patients,respectively.No patient had esophageal involvement.In total,19/41(46.3%) patients exhibited true-positive 18F-FDG uptake in the lesions present in their gastrointestinal tract.In contrast,false-negative 18F-FDG uptake was detected in 24 patients(58.5%),while false-positive 18F-FDG uptake was detected in 5 patients(12.2%).In the former case,2/19 patients had both 18F-FDG-positive lesions and 18F-FDGnegative lesions in the gastrointestinal tract.In patients with 18F-FDG avidity,the SUVmax value of the involved gastrointestinal tract ranged from 2.6 to 17.4(median:4.7).For the 18F-FDG-negative(n = 22) and-positive(n = 19) groups,there were no differences in the male to female ratios(10/12 vs 4/15,P = 0.186),patient age(63.6 ± 2.4 years vs 60.1 ± 2.6 years,P = 0.323),presence of histopathological grade 1 vs 2(20/2 and 17/2,P = 1.000),follicular dendritic cell pattern(duodenal/nodal:13/5 vs 10/3,P = 1.000),mitotic rate(low/partly high,14/1 vs 10/3,P = 0.311),clinical stage according to the Ann Arbor system(stages ⅠE and ⅡE/other,15/7 vs 15/4,P = 0.499),clinical stage according to the Lugano system(stages Ⅰ and Ⅱ-1/other,14/8 vs 14/5,P = 0.489),soluble interleukin-2 receptor levels(495 ± 78 vs 402 ± 83,P = 0.884),LDH levels(188 ± 7 vs 183 ± 8,P = 0.749),hemoglobin levels(13.5 ± 0.3 vs 12.8 ± 0.4,P = 0.197),bone marrow involvement(positive/negative,1/8 vs 1/10,P = 1.000),detectability by CT scanning(positive/negative,1/16 vs 4/13,P = 0.335),and FLIPI risk(low risk/other,16/6 vs 13/6,P = 0.763),respectively in each case.CONCLUSION:These findings indicate that it is not feasible to predict 18F-FDG-avidity.Therefore,18FFDG-PET scans represent a complementary modality for the detection of gastrointestinal involvements in follicular lymphoma patients,and surveillance of the entire gastrointestinal tract by endoscopic examinations is required.     

Hodgkin lymphoma patients in first remission: routine positron emission tomography/computerized tomography imaging is not superior to clinical follow‐up for patients with no residual mass

There is no consensus regarding optimal follow‐up mode for Hodgkin lymphoma (HL) patients that achieve complete remission following chemotherapy or combined chemo‐ and radiation therapy. Several studies demonstrated high sensitivity of positron emission tomography/computerized tomography (PET/CT) in detecting disease progression; however, these techniques are currently not recommended for routine follow‐up. This retrospective study conducted in two Israeli (N = 291) and one New Zealand academic centres (N = 77), compared a group of HL patients, followed‐up with routine imaging every 6 months during the first 2 years after achieving remission, once in the third year, with additional dedicated studies performed due to symptoms or physical findings (Group I) to a group of patients without residual masses who underwent clinically‐based surveillance with dedicated imaging upon relapse suspicion (Group II). Five‐year overall survival (OS) was 94% and median time to relapse was 8·6 months for both modes. Relapse rates in Groups I and II were 13% and 9%, respectively. During the first 3 years of follow‐up, 47·5 and 4·7 studies were performed per detected relapse in Groups I and II, respectively. The current study demonstrated no benefit in either progression‐free survival (PFS) or OS in HL patients followed by routine imaging versus clinical follow‐up. The cost was 10 times higher for routine imaging.     

The value of positron emission tomography in the clinical evaluation of dementia

Positron emission tomography (PET) has been promoted as a means of improving the diagnosis of Alzheimer's disease (AD), but the evidence to support its incremental value is unclear. To assess the evidence regarding the use of PET in the clinical evaluation of AD, a systematic review of the English-language literature indexed in MEDLINE (1975-January 2001), the Cochrane Library (issue 4, 2000), and health technology assessment (HTA) reports was conducted. Articles identified by this review process were graded for methodological and reporting quality using a standardized grading scheme. Sixteen original articles and seven HTA reports were identified. In general, the articles addressed: using PET to differentiate AD from normal aging or non-Alzheimer's dementias, PET imaging compared with single positron emission computed tomography imaging, using PET to predict the progression of dementia, and agreement and reliability in the interpretation of PET images. Serious problems with study design and methodology in all articles were identified. Previous HTA reports have generally recommended that PET not be used in the clinical evaluation of dementia. In conclusion, there is little evidence to support the addition of PET to the routine clinical evaluation of patients with suspected or established dementia. Suggestions for future research in this area are offered.     

18FDG positron emission tomography versus 67Ga scintigraphy as prognostic test during chemotherapy for non-Hodgkin's lymphoma

A prospective study was performed, comparing gallium scintigraphy (67Ga) and positron emission tomography (PET) using fluorine-18 fluorodeoxyglucose (18FDG), to monitor the response of aggressive non-Hodgkin's lymphoma during treatment. 67Ga and 18FDG scans were performed in 26 patients after two cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) therapy. The scans were reviewed independently by four experienced nuclear physicians, who were blinded for the alternative scan technique and follow-up. Eleven out of 26 patients remained free from progression with a mean follow up of 25 +/- 5 months, whereas 14 patients relapsed, and one died of lung cancer. Interobserver variation was significantly greater for 67Ga than for 18FDG PET. Some 64% of patients who had a negative early restaging 18FDG PET remained free from progression versus 50% of patients with negative 67Ga scans. Only 25% of patients with a positive PET remained disease free versus 42% of 67Ga-positive patients. Time to progression was associated with 18FDG PET results, but not with those by 67Ga. 18FDG PET had better test characteristics than 67Ga for the evaluation of early response in aggressive non-Hodgkin's lymphoma patients.     

Prognostic value of positron emission tomography in the evaluation of post-treatment residual mass in patients with Hodgkin's disease and non-Hodgkin's lymphoma

The prognostic value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the assessment of post-treatment residual masses in patients with Hodgkin's disease (HD) or non-Hodgkin's lymphomas (NHL) was evaluated. We prospectively studied 58 patients with HD (n = 43) or NHL (n = 15) who had post-therapeutic complete remission with residual masses (CRu) indicated by computerized tomography. Analysis of 62 residual locations by FDG-PET was performed separately for HD and NHL. Patients with a PET-positive residual mass [standardized uptake value (SUV) > 3] had a recurrence rate of 62.5% (5/8 patients), whereas patients with PET-negative residual mass (SUV < or =3.0) showed a recurrence rate of 4% (2/50 patients, P = 0.004). A positive FDG-PET study correlated with a significantly poorer progression-free survival (P < 0.00001). No recurrence occurred in any of the 39 HD patients with a negative PET scan (negative predictive value, 100%). Four out of four NHL patients with a positive PET study relapsed (positive predictive value, 100%). In conclusion, FDG-PET is a suitable non-invasive method with a high degree of accuracy in the prediction of early recurrence in lymphoma patients with CRu.     

Predictive value of early 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) during salvage chemotherapy in relapsing/refractory Hodgkin lymphoma (HL) treated with high-dose chemotherapy

This retrospective study evaluated whether early 2-[fluorine-18]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) after two cycles of salvage chemotherapy (PET2) could predict survival after high-dose chemotherapy (HDC). Twenty-four Hodgkin lymphoma (HL) patients were included. PET2 was negative in 58% and positive in 42% of patients. Ninety per cent of patients (9/10) with positive PET2 relapsed after HDC while all but one patient with negative PET2 maintained a complete remission. The 2-year progression-free survival was 93% vs. 10% for patients with negative and positive PET2, respectively ( P  < 0.001). This study shows that interim PET can predict the outcome after high-dose chemotherapy in HL patients.     

The role of PET imaging in lymphoma

Positron emission tomography using fluorine-18 (FDG-PET) is increasingly used in the staging and follow-up of malignant lymphomas, although its precise role has not yet been determined. This review considers the results reported at the different stages in the disease history and separately considers the major histological subtypes. Attention is given to the situations in which PET scanning is most likely to influence management. Finally, this review discusses ongoing developments in PET scanning with improved resolution and different radiolabelled tracers.     

Elevated serum levels of soluble CD44 variant 6 are correlated with shorter survival in aggressive non-Hodgkin's lymphoma

A variant form of CD44 that has additional amino acids in the common protein backbone (CD44-v6) seems to play a role in the metastasis of malignancies. We measured soluble CD44-v6 (sCD44-v6) by ELISA in 201 patients with malignant lymphoma. The sCD44-v6 level was significantly elevated in patients with non-Hodgkin's lymphoma (NHL) (n = 184). The sCD44-v6 level was correlated significantly with the standard sCD44 and soluble interleukin-2 receptor levels, but only weakly with serum lactate dehydrogenase (LDH). In 149 patients with aggressive NHL, the sCD44-v6 level was elevated in the subgroups with a high LDH level, stage III/IV disease, T-cell lymphoma, and high-intermediate or high risk group as identified by the International Prognostic Index (IPI). When the sCD44-v6 level was > or = 800 ng/ml the overall survival rate was significantly decreased (p = 0.0001). In the low + low-intermediate risk group (IPI) both overall survival rates (log-rank p = 0.0005, Wilcoxon p =0.002) were significantly decreased when the sCD44-v6 level was > or = 800 ng/ml. In multivariate analysis, sCD44-v6 was shown to be independent of the five prognostic factors in the IPI (age, performance status, number of extranodal sites, Ann Arbor stage and LDH level), so it may be useful for predicting the outcome of aggressive NHL.