Anne Lerberg Nielsen

Routine Bone Marrow Biopsy Has Little or No Therapeutic Consequence for Positron Emission Tomography/Computed Tomography–Staged Treatment-Naive Patients With Hodgkin Lymphoma

PURPOSE To investigate whether bone marrow biopsy (BMB) adds useful information to [(18)F]fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) staging in patients with Hodgkin lymphoma (HL). PATIENTS AND METHODS Newly diagnosed patients with HL undergoing a pretherapeutic staging that encompasses both PET/CT and BMB were included in this retrospective study. The pattern of skeletal FDG uptake was categorized as uni-, bi-, or multifocal (≥ three lesions). Clinical stage, risk assessment, and treatment plan were determined with and without the contribution of BMB results according to the Ann Arbor classification and the guidelines from the German Hodgkin Study Group. RESULTS A total of 454 patients with HL were included of whom 82 (18%) had focal skeletal PET/CT lesions and 27 (6%) had positive BMB. No patients with positive BMB were assessed as having stage I to II disease by PET/CT staging. BMB upstaged five patients, assessed as being stage III before BMB; none of the 454 patients would have been allocated to another treatment on the basis of BMB results. Focal skeletal PET/CT lesions identified positive and negative BMBs with a sensitivity and specificity of 85% and 86%, respectively. The positive and negative predictive values of focal skeletal PET/CT lesions for BMB results were 28% and 99%, respectively. CONCLUSION A consistent finding of this study was the absence of positive BMBs in PET/CT-assessed stage I to II disease. The omission of staging BMB would not have changed the risk assessment or treatment strategy in this cohort of 454 newly diagnosed patients with HL.

MRI, PET/CT and ultrasound in the preoperative staging of endometrial cancer - a multicenter prospective comparative study.

OBJECTIVES The aim of this prospective multicenter study was to evaluate and compare the diagnostic performance of PET/CT, MRI and transvaginal two-dimensional ultrasound (2DUS) in the preoperative assessment of endometrial cancer (EC). METHODS 318 consecutive women with EC were included when referred to three Danish tertiary gynecological centers for surgical treatment. Preoperatively they were PET/CT-, MRI-, and 2DUS scanned. The imaging results were compared to the final pathological findings. This study was approved by the National Committee on Health Research Ethics. RESULTS For predicting myometrial invasion, we found sensitivity, specificity, PPV, NPV, and accuracy for PET/CT to be 93%, 49%, 41%, 95% and 61%, for MRI to be 87%, 57%, 44%, 92%, and 66% and for 2DUS to be 71%, 72%, 51%, 86% and 72%. For predicting cervical invasion, the values were 43%, 94%, 69%, 85% and 83%, respectively, for PET/CT, 33%, 95%, 60%, 85%, and 82%, respectively, for MRI, and 29%, 92%, 48%, 82% and 78% for 2DUS. Finally, for lymph node metastases, the values were 74%, 93%, 59%, 96%, and 91% for PET/CT and 59%, 93%, 40%, 97% and 90% for MRI. When comparing the diagnostic performance we found PET/CT, MRI and 2DUS to be comparable in predicting myometrial invasion. For cervical invasion and lymph node metastases, however, PET/CT was the best. CONCLUSIONS None of the modalities can yet replace surgical staging. However, they all contributed to important knowledge and were, furthermore, able to upstage low-risk patients who would not have been recommended lymph node resection based on histology and grade alone.

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

SUVmax of 18FDG PET/CT as a predictor of high-risk endometrial cancer patients

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.

18F-fluoro-deoxy-glucose-positron emission tomography/computed tomography in diagnosis of head and neck squamous cell carcinoma : A systematic review and meta-analysis

OBJECTIVE To evaluate SUVmax in the assessment of endometrial cancer preoperatively with particular focus on myometrial invasion (MI), cervical invasion (CI), FIGO stage, risk-stratification and lymph node metastases (LNM). METHODS A total of 268 women with endometrial cancer or atypical endometrial hyperplasia underwent FDG PET/CT imaging before surgical treatment. SUVmax of the primary tumour was compared with histological prognostic factors. RESULTS SUVmax was significantly higher in patients with high FIGO stages (p<0.0001), deep MI (p=0.002), CI (p=0.04), LNM (p=0.04) and high risk tumours (p=0.003). Linear regression found that SUVmax was dependent of MI (p=0.001, 95% CI 2.863-11.098), CI (p=0.001, 95% CI 2.896-11.499), risk (p=0.004, 95% CI 0.077-0.397), LNM (p=0.04, 95% CI 0.011-0.482) and FIGO stage (p<0.0001, 95% CI 0.158-0.473). CONCLUSIONS Preoperative PET/CT scanning and SUVmax measurements of the primary tumour may provide additional clinical and prognostic information about MI, CI, LNM and high risk disease in patients with endometrial cancer and allow for individualization of patient care. However, the sensitivity and specificity of the SUVmax in staging endometrial cancer is not high enough to reliably replace surgical staging.

PET/CT without capacity limitations: a Danish experience from a European perspective

UNLABELLED 18F-fluoro-deoxy-glucose-positron emission tomography/computed tomography-scan (PET/CT) is used increasingly for detection of cancer. Precise diagnostic assessment of tumour extension in head and neck squamous cell carcinoma (HNSCC) is of critical importance for ensuring that patients receive proper treatment. Preliminary studies have shown divergent results of PET/CT in diagnosis and staging of HNSCC. The aims of this study were (1) to systematically review and meta-analyse published data about the diagnostic accuracy of PET/CT for diagnosing patients with HNSCC and (2) to compare the diagnostic accuracy of PET/CT with that of standard conventional imaging (SCI). METHODS A systematic literature search in the PubMed, Embase and Cochrane databases on publications of PET/CT diagnostics of HNSCC from January 2005 to July 2013 was carried out. All retrieved studies were reviewed and qualitatively analysed. Along with the calculated pooled sensitivity and specificity of PET/CT and SCI, bubble- and summary receiver operating characteristics (SROC) plots were created. FINDINGS Two meta-analyses of diagnostic accuracy were conducted. The first, on PET/CT, included 987 patients distributed across nine studies. The second, on SCI, included 517 patients participating in a total of six studies among those comparing PET/CT to SCI. The meta-analyses showed a pooled sensitivity of 89.3% (95% confidence interval [95% CI]: 83.4-93.2%) and specificity of 89.5% (95% CI: 82.9-93.7%) for PET/CT and correspondingly, a pooled sensitivity and specificity of 71.6% (95% CI: 44.3-88.9%) and 78.0% (95%CI: 30.2-96.7%) for SCI. A graphical comparison to SCI showed a clear difference in favour of PET/CT. INTERPRETATION PET/CT is highly accurate in diagnosing patients suffering from HNSCC.

Impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography staging in newly diagnosed classical Hodgkin lymphoma: fewer cases with stage I disease and more with skeletal involvement

ObjectivesWe report the 3-year clinical experience of a large new Danish PET/CT centre without capacity limitations in relation to national and European developments.MethodsThe use of PET/CT in cancer was registered from early 2006 to early 2009 to judge the impact on patient management and to compare it with national and European trends.Results6056 PET/CT examinations were performed in 4327 patients. Activity increased by 86 examinations per month compared with the same month the year before. Referrals came primarily from oncology (23.0%), haematology (21.6%), surgery (12.6%), internal medicine (12.7%) and gynaecology (5.5%). Referral indications were diagnosis (31.3%), staging (22.3%), recurrence detection (21.2%), response evaluation (17.0%) and other (8.2%). Response from nearly 60% of users showed that PET/CT caused a change in diagnosis and/or staging and/or treatment plan in 36.0% of cases. During the study period, there was a steep increase in the national use of FDG and in the European use of PET/CT.ConclusionsWe recorded a constantly increasing use of PET/CT that caused a change in diagnosis and/or staging and/or treatment plan in 36.0% of cases. In line with national and European trends this may suggest a shift in favour of functional rather than anatomical imaging.

Impact of Personal Characteristics and Technical Factors on Quantification of Sodium 18F-Fluoride Uptake in Human Arteries: Prospective Evaluation of Healthy Subjects

Abstract 18F-Fluorodeoxyglucose positron emission tomography/ computed tomography (PET/CT) is a highly accurate staging method in classical Hodgkin lymphoma (cHL). We retrospectively compared the staging results obtained in two large cohorts of patients with cHL diagnosed before (n = 324) and after (n = 406) the introduction of PET/CT staging in a retrospective study. In PET/CT staged patients, stage I disease was less frequent (16% vs. 27%, p < 0.001) while stage IV disease was more frequent (17% vs. 10%, p = 0.02). Imaging-detected skeletal involvement was recognized more often in PET/CT staged patients (17% vs. 2%, p < 0.001), and the presence of focal skeletal PET/CT lesions was associated with higher risk of progression (hazard ratio [HR] 1.96, 95% confidence interval [CI]: 1.14–3.36). The German Hodgkin Study Group (GHSG) risk classification (early, intermediate, advanced disease) predicted outcome in PET/CT staged patients. In conclusion, PET/CT led to higher disease stages, and the more frequently diagnosed skeletal lesions may be an adverse prognostic factor.

Utility of interim and end-of-treatment PET/CT in peripheral T-cell lymphomas: A review of 124 patients

Sodium 18F-fluoride (18F-NaF) PET/CT imaging is a promising imaging technique for the assessment of atherosclerosis but is hampered by a lack of validated quantification protocols. Both personal characteristics and technical factors can affect quantification of arterial 18F-NaF uptake. This study investigated whether blood activity, renal function, injected dose, circulating time, and PET/CT system affect quantification of arterial 18F-NaF uptake. Methods: Eighty-nine healthy subjects were prospectively examined by 18F-NaF PET/CT imaging. Arterial 18F-NaF uptake was quantified at the level of the ascending aorta, aortic arch, descending thoracic aorta, and coronary arteries by calculating the maximum 18F-NaF activity (NaFmax), the maximum/mean target-to-background ratio (TBRmax/mean), and the maximum blood-subtracted 18F-NaF activity (bsNaFmax). Multivariable linear regression assessed the effect of personal characteristics and technical factors on quantification of arterial 18F-NaF uptake. Results: NaFmax and TBRmax/mean were dependent on blood activity (β = 0.34 to 0.44, P < 0.001, and β = −0.68 to −0.58, P < 0.001, respectively) and PET/CT system (β = −0.80 to −0.53, P < 0.001, and β = −0.80 to −0.23, P < 0.031, respectively). bsNaFmax depended on PET/CT system (β = −0.91 to −0.57, P < 0.001) but not blood activity. This finding was observed at the level of the ascending aorta, aortic arch, descending thoracic aorta, and the coronary arteries. In addition to blood activity and PET/CT system, injected dose affected quantification of arterial 18F-NaF uptake, whereas renal function and circulating time did not. Conclusion: The prospective evaluation of 89 healthy subjects demonstrated that quantification of arterial 18F-NaF uptake is affected by blood activity, injected dose, and PET/CT system. Therefore, blood activity, injected dose, and PET/CT system should be considered to generate accurate estimates of arterial 18F-NaF uptake.

Head-to-head comparison of chest x-ray/head and neck MRI, chest CT/head and neck MRI, and (18)F-FDG-PET/CT for detection of distant metastases and synchronous cancer in oral, pharyngeal, and laryngeal Cancer

According to the updated guidelines for imaging in lymphoma, 18F‐FDG positron emission tomography/computed tomography (PET/CT) is recommended for staging and evaluation of treatment response in FDG‐avid lymphomas. The purpose of the study was to evaluate the utility of PET/CT in nodal peripheral T‐cell lymphomas (PTCL). Patients with newly diagnosed nodal PTCL (peripheral T‐cell lymphoma NOS, anaplastic large‐cell lymphoma, or angioimmunoblastic T‐cell lymphoma) seen at five Danish hematology centers during the period 2006 to 2012 were included, if they had been pretherapeutically staged with PET/CT. Medical records were reviewed for baseline clinical and follow‐up information. Staging, interim (I‐PET), and end‐of‐treatment PET/CT (E‐PET) studies were centrally reviewed, and reported using the Deauville 5‐point score (DS). A total of 124 patients fulfilled the inclusion criteria. The median age was 58 years, and 88% received CHOP/CHOP‐like therapy. Five years PFS and OS of the study population was 36.8% (95% CI 27.3–46.4) and 49.7% (95% CI 38.9–59.6), respectively. The presence of PET/CT‐ascertained lung and/or liver involvement was associated with a worse outcome. The sensitivity of PET/CT for detecting biopsy‐defined bone marrow involvement was only 18% (95% CI 4–43). An interim DS >3 was not prognostic for worse OS and PFS among CHOP/CHOP‐like treated patients in uni‐ or multivariate analyses. A DS >3 after treatment predicted a worse prognosis. In conclusion, I‐PET was not predictive of outcome in CHOP/CHOP‐like treated PTCL patients when using the DS. Prospective studies are needed to determine the optimal use of PET/CT in PTCL including the role of quantitative PET/CT analysis. Am. J. Hematol. 90:975–980, 2015.