Metabolic Tumor Volume Metrics in Lymphoma Kostakoglu, Lale; Chauvie, Stéphane
Seminars in nuclear medicine,
January 2018, 2018-Jan, 2018-01-00, 20180101, Letnik:
48, Številka:
1
Journal Article
Recenzirano
Although visual assessment using the Deauville criteria is strongly recommended by guidelines for treatment response monitoring in all FDG-avid lymphoma histologies, the high rate of false-positives ...and concerns about interobserver variability have motivated the development of quantitative tools to facilitate objective measurement of tumor response in both routine and clinical trial settings. Imaging studies using functional quantitative measures play a significant role in profiling oncologic processes. These quantitative metrics allow for objective end points in multicenter clinical trials. However, the standardization of imaging procedures including image acquisition parameters, reconstruction and analytic measures, and validation of these methods are essential to enable an individualized treatment approach. A robust quality control program associated with the inclusion of proper scanner calibration, cross-calibration with dose calibrators and across other scanners is required for accurate quantitative measurements. In this section, we will review the technical and methodological considerations related to PET-derived quantitative metrics and the relevant published data to emphasize the potential value of these metrics in the prediction of patient prognosis in lymphoma.
Purpose
Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) is included in the International Myeloma Working Group (IMWG) imaging guidelines for the work-up at diagnosis ...and the follow-up of multiple myeloma (MM) notably because it is a reliable tool as a predictor of prognosis. Nevertheless, none of the published studies focusing on the prognostic value of PET-derived features at baseline consider tumor heterogeneity, which could be of high importance in MM. The aim of this study was to evaluate the prognostic value of baseline PET-derived features in transplant-eligible newly diagnosed (TEND) MM patients enrolled in two prospective independent European randomized phase III trials using an innovative statistical random survival forest (RSF) approach.
Methods
Imaging ancillary studies of IFM/DFCI2009 and EMN02/HO95 trials formed part of the present analysis (IMAJEM and EMN02/HO95, respectively). Among all patients initially enrolled in these studies, those with a positive baseline FDG-PET/CT imaging and focal bone lesions (FLs) and/or extramedullary disease (EMD) were included in the present analysis. A total of 17 image features (visual and quantitative, reflecting whole imaging characteristics) and 5 clinical/histopathological parameters were collected. The statistical analysis was conducted using two RSF approaches (train/validation + test and additional nested cross-validation) to predict progression-free survival (PFS).
Results
One hundred thirty-nine patients were considered for this study. The final model based on the first RSF (train/validation + test) approach selected 3 features (treatment arm, hemoglobin, and SUV
max
Bone Marrow (BM)) among the 22 involved initially, and two risk groups of patients (good and poor prognosis) could be defined with a mean hazard ratio of 4.3 ± 1.5 and a mean log-rank
p
value of 0.01 ± 0.01. The additional RSF (nested cross-validation) analysis highlighted the robustness of the proposed model across different splits of the dataset. Indeed, the first features selected using the train/validation + test approach remained the first ones over the folds with the nested approach.
Conclusion
We proposed a new prognosis model for TEND MM patients at diagnosis based on two RSF approaches.
Trial registration
IMAJEM: NCT01309334 and EMN02/HO95: NCT01134484
At present, there are no standard criteria that have been validated for interim PET reporting in lymphoma. In 2009, an international workshop attended by hematologists and nuclear medicine experts in ...Deauville, France, proposed to develop simple and reproducible rules for interim PET reporting in lymphoma. Accordingly, an international validation study was undertaken with the primary aim of validating the prognostic role of interim PET using the Deauville 5-point score to evaluate images and with the secondary aim of measuring concordance rates among reviewers using the same 5-point score. This paper focuses on the criteria for interpretation of interim PET and on concordance rates.
A cohort of advanced-stage Hodgkin lymphoma patients treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) were enrolled retrospectively from centers worldwide. Baseline and interim scans were reviewed by an international panel of 6 nuclear medicine experts using the 5-point score.
Complete scan datasets of acceptable diagnostic quality were available for 260 of 440 (59%) enrolled patients. Independent agreement among reviewers was reached on 252 of 260 patients (97%), for whom at least 4 reviewers agreed the findings were negative (score of 1-3) or positive (score of 4-5). After discussion, consensus was reached in all cases. There were 45 of 260 patients (17%) with positive interim PET findings and 215 of 260 patients (83%) with negative interim PET findings. Thirty-three interim PET-positive scans were true-positive, and 12 were false-positive. Two hundred three interim PET-negative scans were true-negative, and 12 were false-negative. Sensitivity, specificity, and accuracy were 0.73, 0.94, and 0.91, respectively. Negative predictive value and positive predictive value were 0.94 and 0.73, respectively. The 3-y failure-free survival was 83%, 28%, and 95% for the entire population and for interim PET-positive and -negative patients, respectively (P < 0.0001). The agreement between pairs of reviewers was good or very good, ranging from 0.69 to 0.84 as measured with the Cohen kappa. Overall agreement was good at 0.76 as measured with the Krippendorf α.
The 5-point score proposed at Deauville for reviewing interim PET scans in advanced Hodgkin lymphoma is accurate and reproducible enough to be accepted as a standard reporting criterion in clinical practice and for clinical trials.
Objective
To enhance the positive predictive value (PPV) of chest digital tomosynthesis (DTS) in the lung cancer detection with the analysis of radiomics features.
Method
The investigation was ...carried out within the SOS clinical trial (NCT03645018) for lung cancer screening with DTS. Lung nodules were identified by visual analysis and then classified using the diameter and the radiological aspect of the nodule following lung-RADS. Haralick texture features were extracted from the segmented nodules. Both semantic variables and radiomics features were used to build a predictive model using logistic regression on a subset of variables selected with backward feature selection and using two machine learning: a Random Forest and a neural network with the whole subset of variables. The methods were applied to a train set and validated on a test set where diagnostic accuracy metrics were calculated.
Results
Binary visual analysis had a good sensitivity (0.95) but a low PPV (0.14). Lung-RADS classification increased the PPV (0.19) but with an unacceptable low sensitivity (0.65). Logistic regression showed a mildly increased PPV (0.29) but a lower sensitivity (0.20). Random Forest demonstrated a moderate PPV (0.40) but with a low sensitivity (0.30). Neural network demonstrated to be the best predictor with a high PPV (0.95) and a high sensitivity (0.90).
Conclusions
The neural network demonstrated the best PPV. The use of visual analysis along with neural network could help radiologists to reduce the number of false positive in DTS.
Key Points
•
We investigated several approaches to enhance the positive predictive value of chest digital tomosynthesis in the lung cancer detection.
•
Neural network demonstrated to be the best predictor with a nearly perfect PPV.
•
Neural network could help radiologists to reduce the number of false positive in DTS.
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.
Methods
After primary treatment, biochemical relapse (BCR) occurs in a substantial number of patients with prostate cancer (PCa). PET/CT imaging with prostate-specific membrane antigen based tracers ...(68Ga-PSMA) has shown promising results for BCR patients. However, a standardized image interpretation methodology has yet to be properly agreed. The aim of this study, which was promoted and funded by European Association of Nuclear Medicine (EANM), is to define standardized image interpretation criteria for 68Ga-PSMA PET/CT to detect recurrent PCa lesions in patients treated with primary curative intent therapy (radical prostatectomy or radiotherapy) who presented a biochemical recurrence. In the first phase inter-rater agreement between seven readers from seven international centers was calculated on the reading of 68Ga-PSMA PET/CT images of 49 patients with BCR. Each reader evaluated findings in five different sites of recurrence (local, loco-regional lymph nodes, distant lymph nodes, bone, and other). In the second phase the re-analysis was limited to cases with poor, slight, fair, or moderate agreement Krippendorff’s (K) alpha<0.61. Finally, on the basis of the consensus readings, we sought to define a list of revised consensus criteria for 68Ga-PSMA PET/CT interpretation.
Results
Between-reader agreement for the presence of anomalous findings in any of the five sites was only moderate (K’s alpha: 0.47). The agreement improved and became substantial when readers had to judge whether the anomalous findings were suggestive for a pathologic, uncertain, or non-pathologic image (K’s alpha: 0.64). K’s alpha calculations for each of the five sites of recurrence were also performed and evaluated. First Delphi round was thus conducted. A more detailed definition of the criteria was proposed by the project coordinator, which was then discussed and finally agreed by the seven readers. After the second Delphi round only four cases of disagreement still remained. These were evaluated for a final round, allowing a final agreement table to be written.
Conclusion
We hope that by developing these consensus guidelines on the interpretation of 68Ga-PSMA PET/CT, clinicians reporting these studies will be able to provide more consistent clinical reports and that within clinical trials, abnormality classifications will be harmonized, allowing more robust assessment of its diagnostic performance.
Lymphoma is a potentially curable disease; however, the clinical challenge lies in further improvement of outcomes. PET with fludeoxyglucose is an effective imaging tool. PET-derived quantitative ...metrics have raised significant interest to be used as a prognostic factor to complement clinical parameters for treatment decisions. The most optimized use of these quantitative PET metrics, however, will be possible with the standardization of imaging procedures. In this article, we review the technical and methodological considerations related to PET-derived quantitative metrics, and the relevant published data to emphasize the potential value of these metrics in patient prognosis and treatment response in lymphoma.
Imaging biomarkers (IBs) have been proposed in medical literature that exploit images in a quantitative way, going beyond the visual assessment by an imaging physician. These IBs can be used in the ...diagnosis, prognosis, and response assessment of several pathologies and are very often used for patient management pathways. In this respect, IBs to be used in clinical practice and clinical trials have a requirement to be precise, accurate, and reproducible. Due to limitations in imaging technology, an error can be associated with their value when considering the entire imaging chain, from data acquisition to data reconstruction and subsequent analysis. From this point of view, the use of IBs in clinical trials requires a broadening of the concept of quality assurance and this can be a challenge for the responsible medical physics experts (MPEs). Within this manuscript, we describe the concept of an IB, examine some examples of IBs currently employed in clinical practice/clinical trials and analyze the procedure that should be carried out to achieve better accuracy and reproducibility in their use. We anticipate that this narrative review, written by the components of the EFOMP working group on “the role of the MPEs in clinical trials”-imaging sub-group, can represent a valid reference material for MPEs approaching the subject.
Summary
Interim 2‐18FFluoro‐2‐deoxy‐D‐glucose Positron Emission Tomography performed after two chemotherapy cycles (PET‐2) is the most reliable predictor of treatment outcome in ABVD‐treated Hodgkin ...Lymphoma (HL) patients. We retrospectively analysed the treatment outcome of a therapeutic strategy based on PET‐2 results: positive patients switched to BEACOPP, while negative patients continued with ABVD. Between January 2006 and December 2007, 219 newly diagnosed HL patients admitted to nine centres were enrolled; 54 patients, unfit to receive this treatment were excluded from the analysis. PET‐2 scans were reviewed by a central panel of nuclear medicine experts, according to the Deauville score (Meignan, 2009). After a median follow up of 34 months (12–52) the 2‐year failure free survival (FFS) and overall survival for the entire cohort of 165 patients were 88% and 98%; the FFS was 65% for PET‐2 positive and 92% for PET‐2 negative patients. For 154 patients in which treatment was correctly given according to PET‐2 review, the 2‐year FFS was 91%: 62% for PET‐2 positive and 95% for PET‐2 negative patients. Conclusions: this strategy, with BEACOPP intensification only in PET‐2 positive patients, showed better results than ABVD‐treated historic controls, sparing BEACOPP toxicity to the majority of patients (Clinical Trials.gov Identifier NCT00877747).
The International Extranodal Lymphoma Study Group (IELSG)-37 is a prospective randomized trial assessing the role of consolidation mediastinal radiotherapy after immunochemotherapy to patients with ...newly diagnosed primary mediastinal large B-cell lymphoma (PMBCL). It is a positron emission tomography (PET) response-guided study where patients obtaining a complete metabolic response on an end-of-therapy PET-computed tomography (CT) scan evaluated by a central review are randomized to receive radiotherapy or no further treatment. The aims of this study were to measure agreement between reviewers reporting PET-CT scans for this trial and to determine the effect of training upon concordance rates. The review panel comprised 6 experienced nuclear physicians who read PET-CT scans using the 5-point Deauville scale. Interobserver agreement (IOA) was measured at 4 time points: after a blinded review of a "training set" of 20 patients with PMBCL from the previous IELSG-26 study (phase 1); after the first 10 clinical cases enrolled in the IELSG-37 (phase 2); and after 2 further groups of 50 (phase 3) and 40 clinical cases (phase 4). After feedback from the training set and the first 10 cases, a meeting was held to discuss interpretation, and a detailed set of instructions for the review procedure was agreed and acted upon. Between 2012 and 2014, the first 100 patients were reviewed. Using Deauville score 3 as the cutoff for a complete metabolic response, the overall IOA among the reviewers was good (Krippendorff α = 0.72.) The binary concordance between pairs of reviewers (Cohen κ) ranged from 0.60 to 0.78. The IOA, initially moderate, improved progressively from phase 1 to 4 (Krippendorff α from 0.53 to 0.81; Cohen κ from 0.35-0.72 to 0.77-0.87). Our experience indicates that the agreement among "expert" nuclear physicians reporting PMBCL, even using standardized criteria, was only moderate when the study began. However, agreement improved using a harmonization process, which included a training exercise with discussion of points leading to disagreement and compiling practical rules to sit alongside commonly adopted interpretation criteria.
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