Annika Loft

Early Interim 2-[18F]Fluoro-2-Deoxy-D-Glucose Positron Emission Tomography Is Prognostically Superior to International Prognostic Score in Advanced-Stage Hodgkin's Lymphoma: A Report From a Joint Italian-Danish Study

PURPOSE Starting from November 2001, 260 newly diagnosed patients with Hodgkins lymphoma (HL) were consecutively enrolled in parallel Italian and Danish prospective trials to evaluate the prognostic role of an early interim 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) scan and the International Prognostic Score (IPS) in advanced HL, treated with conventional ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) therapy. PATIENTS AND METHODS Most patients (n = 190) presented with advanced disease (stages IIB through IVB), whereas 70 presented in stage IIA with adverse prognostic factors. All but 11 patients were treated with standard ABVD therapy followed by consolidation radiotherapy in case of bulky presentation or residual tumor mass. Conventional radiologic staging was performed at baseline. FDG-PET scan was performed at baseline and after two courses of ABVD (PET-2). No treatment change was allowed on the basis of the PET-2 results. RESULTS After a median follow-up of 2.19 years (range, 0.32 to 5.18 years), 205 patients were in continued complete remission and two patients were in partial remission. Forty-three patients progressed during therapy or immediately after, whereas 10 patients relapsed. The 2-year progression-free survival for patients with positive PET-2 results was 12.8% and for patients with negative PET-2 results was 95.0% (P < .0001). In univariate analysis, the treatment outcome was significantly associated with PET-2 (P < .0001), stage IV (P < .0001), WBC more than 15,000 (P < .0001), lymphopenia (P < .001), IPS as a continuous variable (P < .0001), extranodal involvement (P < .0001), and bulky disease (P = .012). In multivariate analyses, only PET-2 turned out to be significant (P < .0001). CONCLUSION PET-2 overshadows the prognostic value of IPS and emerges as the single most important tool for planning of risk-adapted treatment in advanced HL.

Preoperative Staging of Lung Cancer with Combined PET–CT

BACKGROUND Fast and accurate staging is essential for choosing treatment for non-small-cell lung cancer (NSCLC). The purpose of this randomized study was to evaluate the clinical effect of combined positron-emission tomography and computed tomography (PET-CT) on preoperative staging of NSCLC. METHODS We randomly assigned patients who were referred for preoperative staging of NSCLC to either conventional staging plus PET-CT or conventional staging alone. Patients were followed until death or for at least 12 months. The primary end point was the number of futile thoracotomies, defined as any one of the following: a thoracotomy with the finding of pathologically confirmed mediastinal lymph-node involvement (stage IIIA [N2]), stage IIIB or stage IV disease, or a benign lung lesion; an exploratory thoracotomy; or a thoracotomy in a patient who had recurrent disease or death from any cause within 1 year after randomization. RESULTS From January 2002 through February 2007, we randomly assigned 98 patients to the PET-CT group and 91 to the conventional-staging group. Mediastinoscopy was performed in 94% of the patients. After PET-CT, 38 patients were classified as having inoperable NSCLC, and after conventional staging, 18 patients were classified thus. Sixty patients in the PET-CT group and 73 in the conventional-staging group underwent thoracotomy (P=0.004). Among these thoracotomies, 21 in the PET-CT group and 38 in the conventional-staging group were futile (P=0.05). The number of justified thoracotomies and survival were similar in the two groups. CONCLUSIONS The use of PET-CT for preoperative staging of NSCLC reduced both the total number of thoracotomies and the number of futile thoracotomies but did not affect overall mortality. (ClinicalTrials.gov number, NCT00867412.)

18F-Fluorodeoxyglucose Positron Emission Tomography Predicts Survival of Patients with Neuroendocrine Tumors

Purpose: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is currently not used on a routine basis for imaging of neuroendocrine (NE) tumors. The aim of this study was to investigate the prognostic value of FDG-PET in patients with NE tumors. Experimental Design: Ninety-eight prospectively enrolled patients with NE tumors underwent FDG-PET imaging. FDG uptake was quantified by maximal standardized uptake value (SUVmax). The prognostic value of FDG uptake, proliferation index, chromogranin A, and liver metastases were assessed. Results: During the 1-year follow-up, 14 patients died. The diagnostic sensitivity of FDG-PET was 58% (n = 57) and a positive FDG-PET result was associated with a significantly higher risk of death with a hazard ratio (HR) of 10.3 [95% confidence interval (CI), 1.3-78.9]. Thirteen of the 57 (23%) FDG-PET–positive patients died compared with 1 of 41 (2%) FDG-PET–negative patients. By univariate analysis, a SUVmax of >9 and a high Ki67 index were significant predictors of overall survival with a HR of 8.8 (95% CI, 2.7-28.7) and a HR of 2.6 (95% CI, 1.3-5.1), respectively. In a multivariate analysis including a SUVmax of >3, Ki67, and chromogranin A, SUVmax of >3 was the only predictor of progression-free survival (HR, 8.4; P < 0.001). Conclusions: This study shows a strong prognostic value of FDG-PET for NE tumors, which exceeds the prognostic value of traditional markers such as Ki67, chromogranin A, and liver metastases. FDG-PET may obtain an important role for NE tumors. Clin Cancer Res; 16(3); 978–85

Concordance between four European centres of PET reporting criteria designed for use in multicentre trials in Hodgkin lymphoma

PurposeTo determine if PET reporting criteria for the Response Adapted Treatment in Hodgkin Lymphoma (RATHL) trial could enable satisfactory agreement to be reached between ‘core’ laboratories operating in different countries.MethodsFour centres reported scans from 50 patients with stage II–IV HL, acquired before and after two cycles of Adriamycin/bleomycin/vinblastine/dacarbazine. A five-point scale was used to score response scans using ‘normal’ mediastinum and liver as reference levels. Centres read scans independently of each other. The level of agreement between centres was determined assuming (1) that uptake in sites involved at diagnosis that was higher than liver uptake represented disease (conservative reading), and (2) that uptake in sites involved at diagnosis that was higher than mediastinal uptake represented disease (sensitive reading).ResultsThere was agreement that the response scan was ‘positive’ or ‘negative’ for lymphoma in 44 patients with a conservative reading and in 41 patients with a sensitive reading. Kappa was 0.85 (95% CI 0.74–0.96) for conservative reading and 0.79 (95% CI 0.67–0.90) for sensitive reading. Agreement was reached in 46 and 44 patients after discussion for the conservative and sensitive readings, respectively.ConclusionThe criteria developed for reporting in the RATHL trial are sufficiently robust to be used in a multicentre setting.

Functional Imaging of Neuroendocrine Tumors: A Head-to-Head Comparison of Somatostatin Receptor Scintigraphy, 123I-MIBG Scintigraphy, and 18F-FDG PET

Functional techniques are playing a pivotal role in the imaging of cancer today. Our aim was to compare, on a head-to-head basis, 3 functional imaging techniques in patients with histologically verified neuroendocrine tumors: somatostatin receptor scintigraphy (SRS) with 111In-diethylenetriaminepentaacetic acid-octreotide, scintigraphy with 123I-metaiodobenzylguanidine (MIBG), and 18F-FDG PET. Methods: Ninety-six prospectively enrolled patients with neuroendocrine tumors underwent SRS, 123I-MIBG scintigraphy, and 18F-FDG PET on average within 40 d. The functional images were fused with low-dose CT scans for anatomic localization, and the imaging results were compared with the proliferation index as determined by Ki67. Results: The overall sensitivity of SRS, 123I-MIBG scintigraphy, and 18F-FDG PET was 89%, 52%, and 58%, respectively. Of the 11 SRS-negative patients, 7 were 18F-FDG PET-positive, of which 3 were also 123I-MIBG scintigraphy–positive, giving a combined overall sensitivity of 96%. SRS also exceeded 123I-MIBG scintigraphy and 18F-FDG PET based on the number of lesions detected (393, 185, and 225, respectively) and tumor subtypes. 123I-MIBG scintigraphy was superior to 18F-FDG PET for ileal neuroendocrine tumors, and 18F-FDG PET was superior to 123I-MIBG scintigraphy for pancreaticoduodenal neuroendocrine tumors. The sensitivity of 18F-FDG PET (92%) exceeded that of both SRS (69%) and 123I-MIBG scintigraphy (46%) for tumors with a proliferation index above 15%. Conclusion: The overall sensitivity of 123I-MIBG scintigraphy and 18F-FDG PET was low compared with SRS. However, for tumors with a high proliferation rate, 18F-FDG PET had the highest sensitivity. The results indicate that, although SRS should still be the routine method, 18F-FDG PET provides complementary diagnostic information and is of value for neuroendocrine tumor patients with negative SRS findings or a high proliferation index.

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.

PET/CT with intravenous contrast can be used for PET attenuation correction in cancer patients

PurposeIf the CT scan of a combined PET/CT study is performed as a full diagnostic quality CT scan including intravenous (IV) contrast agent, the quality of the joint PET/CT procedure is improved and a separate diagnostic CT scan can be avoided. CT with IV contrast can be used for PET attenuation correction, but this may result in a bias in the attenuation factors. The clinical significance of this bias has not been established. Our aim was to perform a prospective clinical study where each patient had CT performed with and without IV contrast agent to establish whether PET/CT with IV contrast can be used for PET attenuation without reducing the clinical value of the PET scan.MethodsA uniform phantom study was used to document that the PET acquisition itself is not significantly influenced by the presence of IV contrast medium. Then, 19 patients referred to PET/CT with IV contrast underwent CT scans without, and then with contrast agent, followed by an 18F-fluorodeoxyglucose whole-body PET scan. The CT examinations were performed with identical parameters on a GE Discovery LS scanner. The PET data were reconstructed with attenuation correction based on the two CT data sets. A global comparison of standard uptake value (SUV) was performed, and SUVs in tumour, in non-tumour tissue and in the subclavian vein were calculated. Clinical evaluation of the number and location of lesions on all PET/CT scans was performed twice, blinded and in a different random order, by two independent nuclear medicine specialists.ResultsIn all patients, the measured global SUV of PET images based on CT with IV contrast agent was higher than the global activity using non-contrast correction. The overall increase in the mean SUV (for two different conversion tables tested) was 4.5±2.3% and 1.6±0.5%, respectively. In 11/19 patients, focal uptake was identified corresponding to malignant tumours. Eight out of 11 tumours showed an increased SUVmax (2.9±3.1%) on the PET images reconstructed using IV contrast. The clinical evaluation performed by the two specialists comparing contrast and non-contrast CT attenuated PET images showed weighted kappa values of 0.92 (doctor A) and 0.82 (doctor B). No contrast-introduced artefacts were found.ConclusionThis study demonstrates that CT scans with IV contrast agent can be used for attenuation correction of the PET data in combined modality PET/CT scanning, without changing the clinical diagnostic interpretation.

The predictive role of interim positron emission tomography for Hodgkin lymphoma treatment outcome is confirmed using the interpretation criteria of the Deauville five-point scale

A retrospective, international, multicenter study was undertaken to assess: (i) the prognostic role of ‘interim’ positron emission tomography performed during treatment with doxorubicin, bleomycin, vinblastine and dacarbazine in patients with Hodgkin lymphoma; and (ii) the reproducibility of the Deauville five-point scale for the interpretation of interim positron emission tomography scan. Two hundred and sixty patients with newly diagnosed Hodgkin lymphoma were enrolled. Fifty-three patients with early unfavorable and 207 with advanced-stage disease were treated with doxorubicin, bleomycin, vinblastine and dacarbazine ± involved-field or consolidation radiotherapy. Positron emission tomography scan was performed at baseline and after two cycles of chemotherapy. Treatment was not changed according to the results of the interim scan. An international panel of six expert reviewers independently reported the scans using the Deauville five-point scale, blinded to treatment outcome. Forty-five scans were scored as positive (17.3%) and 215 (82.7%) as negative. After a median follow up of 37.0 (2–110) months, 252 patients are alive and eight have died. The 3-year progression-free survival rate was 83% for the whole study population, 28% for patients with interim positive scans and 95% for patients with interim negative scans (P<0.0001). The sensitivity, specificity, and negative and positive predictive values of interim positron emission tomography scans for predicting treatment outcome were 0.73, 0.94, 0.94 and 0.73, respectively. Binary concordance amongst reviewers was good (Cohen’s kappa 0.69–0.84). In conclusion, the prognostic role and validity of the Deauville five-point scale for interpretation of interim positron emission tomography scans have been confirmed by the present study.

Prospective study of 18FDG‐PET in the detection and management of patients with lymph node metastases to the neck from an unknown primary tumor. Results from the DAHANCA‐13 study

The benefit of a complementary fluorodeoxyglucose‐positron emission tomography (FDG‐PET) scan to standard workup for carcinoma of unknown primary (CUP) and metastatic neck lesions was prospectively studied.

Contrast-enhanced FDG-PET/CT vs. SPIO-enhanced MRI vs. FDG-PET vs. CT in patients with liver metastases from colorectal cancer: a prospective study with intraoperative confirmation.

Background: The choice of imaging before liver surgery is debated regarding the use of magnetic resonance (MR) imaging, computed tomography (CT), and positron emission tomography (PET). No studies have compared contrast-enhanced PET/CT with superparamagnetic iron oxide (SPIO)-enhanced MR imaging. Purpose: To compare PET/CT with superparamagnetic iron oxide (SPIO)-enhanced MR imaging, PET, and CT in the detection of liver metastases (LM) and extrahepatic tumor from colorectal cancer (CRC). Material and Methods: Thirty-five patients with suspected LM underwent PET/CT with a contrast-enhanced CT protocol and SPIO-enhanced MR imaging. Readers independently analyzed images from MR imaging, PET/CT, and the CT part and PET part of the PET/CT study. Imaging findings were compared with surgical and histological findings. Results: Lesion-by-lesion sensitivity and accuracy for liver lesions was 54% and 77% for PET alone, 66% and 83% for PET/CT, 82% and 82% for SPIO-enhanced MR imaging, and 89% and 77% for CT alone, respectively. CT and SPIO-enhanced MR imaging were less specific but significantly more sensitive than PET (P<0.0001). For extrahepatic tumor, sensitivity and specificity was 83% and 96% for PET/CT and 58% and 87% for CT, respectively. Conclusion: CT and SPIO-enhanced MR imaging are more sensitive but less specific than PET in the detection of LM. PET/CT can detect more patients with extrahepatic tumor than CT alone.