Thyroidectomy without Radioiodine in Patients with Low-Risk Thyroid Cancer.

BACKGROUND: In patients with low-risk differentiated thyroid cancer undergoing thyroidectomy, the postoperative administration of radioiodine (iodine-131) is controversial in the absence of demonstrated benefits. METHODS: In this prospective, randomized, phase 3 trial, we assigned patients with low-risk differentiated thyroid cancer who were undergoing thyroidectomy to receive ablation with postoperative administration of radioiodine (1.1 GBq) after injections of recombinant human thyrotropin (radioiodine group) or to receive no postoperative radioiodine (no-radioiodine group). The primary objective was to assess whether no radioiodine therapy was noninferior to radioiodine therapy with respect to the absence of a composite end point that included functional, structural, and biologic abnormalities at 3 years. Noninferiority was defined as a between-group difference of less than 5 percentage points in the percentage of patients who did not have events that included the presence of abnormal foci of radioiodine uptake on whole-body scanning that required subsequent treatment (in the radioiodine group only), abnormal findings on neck ultrasonography, or elevated levels of thyroglobulin or thyroglobulin antibodies. Secondary end points included prognostic factors for events and molecular characterization. RESULTS: Among 730 patients who could be evaluated 3 years after randomization, the percentage of patients without an event was 95.6% (95% confidence interval [CI], 93.0 to 97.5) in the no-radioiodine group and 95.9% (95% CI, 93.3 to 97.7) in the radioiodine group, a difference of -0.3 percentage points (two-sided 90% CI, -2.7 to 2.2), a result that met the noninferiority criteria. Events consisted of structural or functional abnormalities in 8 patients and biologic abnormalities in 23 patients with 25 events. Events were more frequent in patients with a postoperative serum thyroglobulin level of more than 1 ng per milliliter during thyroid hormone treatment. Molecular alterations were similar in patients with or without an event. No treatment-related adverse events were reported. CONCLUSIONS: In patients with low-risk thyroid cancer undergoing thyroidectomy, a follow-up strategy that did not involve the use of radioiodine was noninferior to an ablation strategy with radioiodine regarding the occurrence of functional, structural, and biologic events at 3 years. (Funded by the French National Cancer Institute; ESTIMABL2 ClinicalTrials.gov number, NCT01837745.).

Respiratory muscle metabolic activity on PET/CT correlates with obstructive ventilatory defect severity and prognosis in patients undergoing lung cancer surgery.

BACKGROUND AND OBJECTIVE: Respiratory muscle activity is increased in patients with chronic respiratory disease. 18 F-FDG-PET/CT can assess respiratory muscle activity. We hypothesized that respiratory muscles metabolism was correlated to lung function impairment and was associated to prognosis in patients undergoing lung cancer surgery based on the research question whether respiratory muscle metabolism quantitatively correlates with the severity of lung function impairment in patients? Does respiratory muscle hypermetabolism have prognostic value? METHODS: Patients undergoing 18 F-FDG-PET/CT and pulmonary function tests prior to lung cancer surgery were identified. Maximum Standardized Uptake Value (SUVm) were measured in each respiratory muscle group (sternocleidomastoid, scalene, intercostal, diaphragm), normalized against deltoid SUVm. Respiratory muscle hypermetabolism was defined as SUVm >90th centile in any respiratory muscle group. Clinical outcomes were collected from a prospective cohort. RESULTS: One hundred fifty-six patients were included, mostly male [110 (71%)], 53 (34%) with previous diagnosis of COPD. Respiratory muscle SUVm were: scalene: 1.84 [1.51-2.25], sternocleidomastoid 1.64 [1.34-1.95], intercostal 1.01 [0.84-1.16], diaphragm 1.79 [1.41-2.27]. Tracer uptake was inversely correlated to FEV1 for the scalene (r = -0.29, p < 0.001) and SCM (r = -0.17, p = 0.03) respiratory muscle groups and positively correlated to TLC for the scalene (r = 0.17, p = 0.04). Respiratory muscle hypermetabolism was found in 45 patients (28.8%), who had a lower VO2 max (15.4 [14.2-17.5] vs. 17.2 mL/kg/min [15.2-21.1], p = 0.07) and poorer overall survival when adjusting to FEV1% (p < 0.01). CONCLUSION: Our findings show respiratory muscle hypermetabolism is associated with lung function impairment and has prognostic significance. 18 F-FDG/PET-CT should be considered as a tool for assessing respiratory muscle activity and to identify high-risk patients.

Joint EANM/SNMMI/ESTRO practice recommendations for the use of 2-[18F]FDG PET/CT external beam radiation treatment planning in lung cancer V1.0.

PURPOSE: 2-[18F]FDG PET/CT is of utmost importance for radiation treatment (RT) planning and response monitoring in lung cancer patients, in both non-small and small cell lung cancer (NSCLC and SCLC). This topic has been addressed in guidelines composed by experts within the field of radiation oncology. However, up to present, there is no procedural guideline on this subject, with involvement of the nuclear medicine societies. METHODS: A literature review was performed, followed by a discussion between a multidisciplinary team of experts in the different fields involved in the RT planning of lung cancer, in order to guide clinical management. The project was led by experts of the two nuclear medicine societies (EANM and SNMMI) and radiation oncology (ESTRO). RESULTS AND CONCLUSION: This guideline results from a joint and dynamic collaboration between the relevant disciplines for this topic. It provides a worldwide, state of the art, and multidisciplinary guide to 2-[18F]FDG PET/CT RT planning in NSCLC and SCLC. These practical recommendations describe applicable updates for existing clinical practices, highlight potential flaws, and provide solutions to overcome these as well. Finally, the recent developments considered for future application are also reviewed.

Deep learning analysis of contrast-enhanced spectral mammography to determine histoprognostic factors of malignant breast tumours.

OBJECTIVE: To evaluate if a deep learning model can be used to characterise breast cancers on contrast-enhanced spectral mammography (CESM). METHODS: This retrospective mono-centric study included biopsy-proven invasive cancers with an enhancement on CESM. CESM images include low-energy images (LE) comparable to digital mammography and dual-energy subtracted images (DES) showing tumour angiogenesis. For each lesion, histologic type, tumour grade, estrogen receptor (ER) status, progesterone receptor (PR) status, HER-2 status, Ki-67 proliferation index, and the size of the invasive tumour were retrieved. The deep learning model used was a CheXNet-based model fine-tuned on CESM dataset. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was calculated for the different models: images by images and then by majority voting combining all the incidences for one tumour. RESULTS: In total, 447 invasive breast cancers detected on CESM with pathological evidence, in 389 patients, which represented 2460 images analysed, were included. Concerning the ER, the deep learning model on the DES images had an AUC of 0.83 with the image-by-image analysis and of 0.85 for the majority voting. For the triple-negative analysis, a high AUC was observable for all models, in particularity for the model on LE images with an AUC of 0.90 for the image-by-image analysis and 0.91 for the majority voting. The AUC for the other histoprognostic factors was lower. CONCLUSION: Deep learning analysis on CESM has the potential to determine histoprognostic tumours makers, notably estrogen receptor status, and triple-negative receptor status. KEY POINTS: • A deep learning model developed for chest radiography was adapted by fine-tuning to be used on contrast-enhanced spectral mammography. • The adapted models allowed to determine for invasive breast cancers the status of estrogen receptors and triple-negative receptors. • Such models applied to contrast-enhanced spectral mammography could provide rapid prognostic and predictive information.

Respiratory gated multistatic PET reconstructions to delineate radiotherapy target volume in patients with mobile lung tumors.

BACKGROUND: PET-CT with 18F-FDG or other radiopharmaceuticals is a recommended tool to help the delineation of lung cancers candidate to radiotherapy. The motion artifacts caused by respiratory movements are reduced by 4D acquisitions. We introduced an extended reconstruction algorithm (multiple reconstruct register and average [multi-RRA]) which requires much shorter acquisition times than standard 4D PET-CT. Our aim was to evaluate the interest on multi-RRA images as an alternative of 3D and 4D PET-CT for the delineation of lung lesion. METHODS: PET acquisitions synchronized to the respiratory signal were obtained in 18 patients with mobile lung tumors. We compared the tumor volumes delineated on Multi-RRA images to 3D and 4D PET-CT, considering the 4D CT as a reference. The tumor volumes were delineated and compared with topologic similarity indexes (Dice, Jaccard and overlap). RESULTS: Twenty tumors were delineated. The volumes delineated with multi-RRA and 4D PET were not significantly different (mean difference of 0.2±0.7 mL). Comparison by pairs (Tukey-Kramer test) showed that 3D-PET volumes were significantly smaller than 4D-PET and multi-RRA volumes (P<0.001). Topologic similarity indexes with 4D-PET were slightly statistically higher with multi-RRA than with 3D-PET (Dice and Jaccard) or 4D-CT (Dice, Jaccard and Overlap). CONCLUSIONS: The tumor volumes delineated on multi-RRA are similar to the volumes obtained with 4D PET, with shorter acquisition time.

Characterization of positioning uncertainties in PET-CT-MR trimodality solutions for radiotherapy.

The purpose of this study was to evaluate the positioning uncertainties of two PET/CT-MR imaging setups, C1 and C2. Because the PET/CT data were acquired on the same hybrid device with automatic image registration, experiments were conducted using CT-MRI data. In C1, a transfer table was used, which allowed the patient to move from one imager to another while maintaining the same position. In C2, the patient stood up and was positioned in the same radiotherapy treatment position on each imager. The two setups provided a set of PET/CT and MR images. The accuracy of the registration software was evaluated on the CT-MRI data of one patient using known translations and rotations of MRI data. The uncertainties on the two setups were estimated using a phantom and a cohort of 30 patients. The accuracy of the positioning uncertainties was evaluated using descriptive statistics and a t-test to determine whether the mean shift significantly deviated from zero (p < 0.05) for each setup. The maximum registration errors were less than 0.97 mm and 0.6° for CT-MRI registration. On the phantom, the mean total uncertainties were less than 2.74 mm and 1.68° for C1 and 1.53 mm and 0.33° for C2. For C1, the t-test showed that the displacements along the z-axis did not significantly deviate from zero (p = 0.093). For C2, significant deviations from zero were present for anterior-posterior and superior-inferior displacements. The mean total uncertainties were less than 4 mm and 0.42° for C1 and less than 1.39 mm and 0.27° for C2 in the patients. Furthermore, the t-test showed significant deviations from zero for C1 on the anterior-posterior and roll sides. For C2, there was a significant deviation from zero for the left-right displacements.This study shows that transfer tables require careful evaluation before use in radiotherapy.

Correction: Brochet et al. A Quantitative Comparison between Shannon and Tsallis-Havrda-Charvat Entropies Applied to Cancer Outcome Prediction. Entropy 2022, 24, 436.

Alexandre Huat, Sébastien Thureau, David Pasquier, Isabelle Gardin, Romain Modzelewski, David Gibon, Juliette Thariat and Vincent Grégoire were not included as authors in the original publication [...].

A Quantitative Comparison between Shannon and Tsallis-Havrda-Charvat Entropies Applied to Cancer Outcome Prediction.

In this paper, we propose to quantitatively compare loss functions based on parameterized Tsallis-Havrda-Charvat entropy and classical Shannon entropy for the training of a deep network in the case of small datasets which are usually encountered in medical applications. Shannon cross-entropy is widely used as a loss function for most neural networks applied to the segmentation, classification and detection of images. Shannon entropy is a particular case of Tsallis-Havrda-Charvat entropy. In this work, we compare these two entropies through a medical application for predicting recurrence in patients with head-neck and lung cancers after treatment. Based on both CT images and patient information, a multitask deep neural network is proposed to perform a recurrence prediction task using cross-entropy as a loss function and an image reconstruction task. Tsallis-Havrda-Charvat cross-entropy is a parameterized cross-entropy with the parameter α. Shannon entropy is a particular case of Tsallis-Havrda-Charvat entropy for α=1. The influence of this parameter on the final prediction results is studied. In this paper, the experiments are conducted on two datasets including in total 580 patients, of whom 434 suffered from head-neck cancers and 146 from lung cancers. The results show that Tsallis-Havrda-Charvat entropy can achieve better performance in terms of prediction accuracy with some values of α.

UMI-VarCal: a new UMI-based variant caller that efficiently improves low-frequency variant detection in paired-end sequencing NGS libraries.

MOTIVATION: Next-generation sequencing has become the go-to standard method for the detection of single-nucleotide variants in tumor cells. The use of such technologies requires a PCR amplification step and a sequencing step, steps in which artifacts are introduced at very low frequencies. These artifacts are often confused with true low-frequency variants that can be found in tumor cells and cell-free DNA. The recent use of unique molecular identifiers (UMI) in targeted sequencing protocols has offered a trustworthy approach to filter out artefactual variants and accurately call low-frequency variants. However, the integration of UMI analysis in the variant calling process led to developing tools that are significantly slower and more memory consuming than raw-reads-based variant callers. RESULTS: We present UMI-VarCal, a UMI-based variant caller for targeted sequencing data with better sensitivity compared to other variant callers. Being developed with performance in mind, UMI-VarCal stands out from the crowd by being one of the few variant callers that do not rely on SAMtools to do their pileup. Instead, at its core runs an innovative homemade pileup algorithm specifically designed to treat the UMI tags in the reads. After the pileup, a Poisson statistical test is applied at every position to determine if the frequency of the variant is significantly higher than the background error noise. Finally, an analysis of UMI tags is performed, a strand bias and a homopolymer length filter are applied to achieve better accuracy. We illustrate the results obtained using UMI-VarCal through the sequencing of tumor samples and we show how UMI-VarCal is both faster and more sensitive than other publicly available solutions. AVAILABILITY AND IMPLEMENTATION: The entire pipeline is available at https://gitlab.com/vincent-sater/umi-varcal-master under MIT license. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Radiotherapy boost in patients with hypoxic lesions identified by 18F-FMISO PET/CT in non-small-cell lung carcinoma: can we expect a better survival outcome without toxicity? [RTEP5 long-term follow-up].

PURPOSE: Chemoradiotherapy is the reference curative-intent treatment for nonresectable locally advanced non-small-cell lung carcinoma (NSCLC), with unsatisfactory survival, partially due to radiation resistance in hypoxic tissues. The objective was to update survival and toxicity at 3 years following radiotherapy boost to hypoxic tumours in NSCLC patients treated with curative-intent chemoradiotherapy. METHODS: This was an open-label, nonrandomized, multicentre, phase II clinical trial. 18F-Fluoromisonidazole (18F-FMISO) PET/CT was used to determine the hypoxic profile of the patients. 18F-FMISO-positive patients and those without organ-at-risk constraints received a radiotherapy boost (70-84 Gy); the others received standard radiotherapy (66 Gy). Overall survival (OS), progression-free survival (PFS) and safety were assessed. RESULTS: A total of 54 patients were evaluated. OS and PFS rates at 3 years were 48.5% and 28.8%, respectively. The median OS in the 18F-FMISO-positive patients was 25.8 months and was not reached in the 18F-FMISO-negative patients (p = 0.01). A difference between the groups was also observed for PFS (12 months vs. 26.2 months, p = 0.048). In 18F-FMISO-positive patients, no difference was observed in OS in relation to dose, probably because of the small sample size (p = 0.30). However, the median OS seemed to be in favour of patients who received the radiotherapy boost (26.5 vs. 15.3 months, p = 0.71). In patients who received the radiotherapy boost, no significant late toxicities were observed. CONCLUSION: 18F-FMISO uptake in NSCLC patients is strongly associated with features indicating a poor prognosis. In 18F-FMISO-positive patients, the radiotherapy boost seemed to improve the OS by 11.2 months. A further clinical trial is needed to investigate the efficacy of a radiotherapy boost in patients with hypoxic tumours.

Diffusion-weighted MRI is not superior to FDG-PET/CT for the detection of neck recurrence in well-differentiated thyroid carcinoma.

BACKGROUND: Management of patients with well-differentiated thyroid carcinoma (WDTC) and positive thyroglobulin (Tg)/negative iodine-131 whole body scintigraphy (WBS) remains challenging. Here, we investigate the specific role of diffusion-weighted magnetic resonance imaging of the neck (DW-MRI) as compared to rhTSH stimulated FDG-PET/CT in such patients. METHODS: Patients with WDTC, positive Tg/negative WBS were prospectively enrolled in the study. FDG-PET/CT and neck DW-MRI were performed on the same day after rhTSH stimulation. Neck-US was performed 24 hours after FDG-PET/CT and MRI to guide fine-needle aspiration (FNA). Patients with positive FNA underwent surgery. Patient with negative workup underwent new explorations at 6 and 18 months. RESULTS: A total of 86 FDG-PET/CT and 83 DW-MRI tests were performed in 40 patients (23 females; 17 males; 52±16 years). For detection of neck recurrences, sensitivity was equivalent for FDG-PET/CT and to DW-MRI at baseline (46% vs. 43%), at 6 months (30% vs. 20%) and at 18 months (11 vs. 10%). The comparison with a non-weighted Kappa test shows significant concordance between FDG-PET/CT and DW-MRI (K=0.741±0.062; P<0.0001). A relationship was observed between Tg and results of FDG-PET/CT, but not for DW-MRI. FDG-PET/CT permitted to detect iodine-refractory distant metastasis in 4 patients. CONCLUSIONS: In Tg-positive/WBS-negative DTC patients, low tumour burden, neck DW-MRI does not provide additional information compared to rhTSH-stimulated FDG-PET/CT. FDG-PET/CT has the best sensitivity, is acceptable for patients, allows whole body exploration and distant metastasis detections, and is correlated with Tg levels.

Anthropometer3D: Automatic Multi-Slice Segmentation Software for the Measurement of Anthropometric Parameters from CT of PET/CT.

Anthropometric parameters like muscle body mass (MBM), fat body mass (FBM), lean body mass (LBM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) are used in oncology. Our aim was to develop and evaluate the software Anthropometer3D measuring these anthropometric parameters on the CT of PET/CT. This software performs a multi-atlas segmentation of CT of PET/CT with extrapolation coefficients for the body parts beyond the usual acquisition range (from the ischia to the eyes). The multi-atlas database is composed of 30 truncated CTs manually segmented to isolate three types of voxels (muscle, fat, and visceral fat). To evaluate Anthropomer3D, a leave-one-out cross-validation was performed to measure MBM, FBM, LBM, VAT, and SAT. The reference standard was based on the manual segmentation of the corresponding whole-body CT. A manual segmentation of one CT slice at level L3 was also used. Correlations were analyzed using Dice coefficient, intra-class coefficient correlation (ICC), and Bland-Altman plot. The population was heterogeneous (sex ratio 1:1; mean age 57 years old [min 23; max 74]; mean BMI 27 kg/m2 [min 18; max 40]). Dice coefficients between reference standard and Anthropometer3D were excellent (mean+/-SD): muscle 0.95 ± 0.02, fat 1.00 ± 0.01, and visceral fat 0.97 ± 0.02. The ICC was almost perfect (minimal value of 95% CI of 0.97). All Bland-Altman plot values (mean difference, 95% CI and slopes) were better for Anthropometer3D compared to L3 level segmentation. Anthropometer3D allows multiple anthropometric measurements based on an automatic multi-slice segmentation. It is more precise than estimates using L3 level segmentation.

Correction to: Tumor fragmentation estimated by volume surface ratio of tumors measured on 18F-FDG PET/CT is an independent prognostic factor of diffuse large B-cell lymphoma.

A unit error concerning the tumor volume surface ratio (TVSR) is present throughout the article. The unit reported is "cm" but is actually "mm".

Tumor fragmentation estimated by volume surface ratio of tumors measured on 18F-FDG PET/CT is an independent prognostic factor of diffuse large B-cell lymphoma.

INTRODUCTION: Our aim was to study the prognostic value of two new 18F-FDG PET biomarkers in diffuse large B-cell lymphoma (DLBCL). We examined the total tumor surface (TTS), describing the tumor-host interface, and the tumor volume surface ratio (TVSR), corresponding to the ratio between the total metabolic tumor volume (TMTV) and TTS, describing the tumor fragmentation. METHODS: We retrospectively included 215 patients with DLBCL. Patients underwent initial 18F-FDG PET/CT before R-CHOP (73%) or intensified R-CHOP (R-ACVBP) regimens (27%). The TMTV was measured using a fixed threshold value of 41% of SUVmax. To calculate TTS and TVSR, the surface was measured using an in-house software based on the marching cube algorithm. Spearman's rank correlation coefficient (ρ) was computed between TMTV, TTS, and TVSR, and ROC analysis was performed. Survival functions at 5 years were studied using a Kaplan-Meier method and uni/multivariate Cox analysis. RESULTS: TVSR was poorly correlated with TMTV (ρ = 0.5) and TTS (ρ = 0.26), while TTS was highly correlated with TMTV (ρ = 0.94) and was, therefore, excluded from the analysis. TMTV had the highest area under the ROC curve (0.711) and the best sensitivity (0.797), while TVSR had the best specificity (0.745). The optimal cut-off values to predict 5-year OS were 222 cm3 for TMTV and 6.0 mm for TVSR. Patients with high TMTV and TVSR had significantly worse prognosis in Kaplan-Meier and Cox univariate analysis. In a multivariate Cox analysis combining the International Prognostic Index (IPI), the type of chemotherapy, TMTV, and TVSR, all parameters were independent and significant prognostic factors (HR [95%CI]: IPI 1.4 [1.1-1.8], type of chemotherapy 4.5 [2.0-10.5], TMTV 2.8 [1.4-5.5], TVSR 2.1 [1.3-3.4]). A synergistic effect between TMTV and TVSR was observed in a Kaplan-Meier analysis combining the two parameters. CONCLUSIONS: TVSR measured on the initial 18F-FDG PET is an independent prognostic factor in DLBCL and has an additional prognostic value when combined with TMTV, IPI score and chemotherapy.

How to use PET/CT in the evaluation of response to radiotherapy.

Radiotherapy is a major treatment modality for many cancers. Tumor response after radiotherapy determines the subsequent steps of the patient's management (surveillance, adjuvant or salvage treatment and palliative care). Tumor response assessed during radiotherapy offers a promising opportunity to adapt the treatment plan to reduced or increased target volume, to specifically target sub-volumes with relevant biological characteristics (metabolism, hypoxia, proliferation, etc.) and to further spare the organs at risk. In addition to its role in the diagnosis and the initial staging, Positron Emission Tomography combined with a Computed Tomography (PET/CT) provides functional information and is therefore attractive to evaluate tumor response. The aim of this paper is to review the published data addressing PET/CT as an evaluation tool in irradiated tumors. Reports on PET/CT acquired at various times (during radiotherapy, after initial (chemo-) radiotherapy, after definitive radiotherapy and during posttreatment follow-up) in solid tumors (lung, head-and-neck, cervix, esophagus, prostate and rectum) were collected and reviewed. Various tracers and technical aspects are also discussed. 18F-FDG PET/CT has a well-established role in clinical routine after definitive chemo-radiotherapy for locally advanced head-and-neck cancers. 18F-choline PET/CT is indicated in prostate cancer patients with biochemical failure. 18F-FDG PET/CT is optional in many other circumstances and the clinical benefits of assessing tumor response with PET/CT remain a field of very active research. The combination of PET with Magnetic Resonance Imaging (PET/MRI) may prove to be valuable in irradiated rectal and cervix cancers. Tumor response can be evaluated by PET/CT with clinical consequences in multiple situations, notably in head and neck and prostate cancers, after radiotherapy. Further clinical evaluation for most cancers is still needed, possibly in association to MRI.

Automatic Measurement of the Total Visceral Adipose Tissue From Computed Tomography Images by Using a Multi-Atlas Segmentation Method.

BACKGROUND: The visceral adipose tissue (VAT) volume is a predictive and/or prognostic factor for many cancers. The objective of our study was to develop an automatic measurement of the whole VAT volume using a multi-atlas segmentation (MAS) method from a computed tomography. METHODS: A total of 31 sets of whole-body computed tomography volume data were used. The reference VAT volume was defined on the basis of manual segmentation (VATMANUAL). We developed an algorithm, which measured automatically the VAT volumes using a MAS based on a nonrigid volume registration algorithm coupled with a selective and iterative method for performance level estimation (SIMPLE), called VATMAS_SIMPLE. The results were evaluated using intraclass correlation coefficient and dice similarity coefficients. RESULTS: The intraclass correlation coefficient of VATMAS_SIMPLE was excellent, at 0.976 (confidence interval, 0.943-0.989) (P < 0.001). The dice similarity coefficient of VATMAS_SIMPLE was also good, at 0.905 (SD, 0.076). CONCLUSIONS: This newly developed algorithm based on a MAS can measure accurately the whole abdominopelvic VAT.

Predictive value of 18F-FDG PET/CT in adults with T-cell lymphoblastic lymphoma: post hoc analysis of results from the GRAALL-LYSA LLO3 trial.

PURPOSE: We examined whether FDG PET can be used to predict outcome in patients with lymphoblastic lymphoma (LL). METHODS: This was a retrospective post hoc analysis of data from the GRAAL-LYSA LL03 trial, in which the treatment of LL using an adapted paediatric-like acute lymphoblastic leukaemia protocol was evaluated. PET data acquired at baseline and after induction were analysed. Maximum standardized uptake values (SUVmax), total metabolic tumour volume and total lesion glycolysis were measured at baseline. The relative changes in SUVmax from baseline (ΔSUVmax) and the Deauville score were determined after induction. RESULTS: The population analysed comprised 36 patients with T-type LL. SUVmax using a cut-off value of ≤8.76 vs. >8.76 was predictive of 3-year event-free survival (31.6% vs. 80.4%; p = 0.013) and overall survival (35.0% vs. 83.7%; p = 0.028). ΔSUVmax using a cut-off value of ≤80% vs. >80% tended also to be predictive of 3-year event-free survival (40.0% vs. 76.0%; p = 0.054) and overall survival (49.2% vs. 85.6%; p = 0.085). Total metabolic tumour volume, baseline total lesion glycolysis and response according to the Deauville score were not predictive of outcome. CONCLUSIONS: A low initial SUVmax was predictive of worse outcomes in our series of patients with T-type LL. Although relatively few patients were included, the study also suggested that ΔSUVmax may be useful for predicting therapeutic efficacy.

18F-FDG-PET partial volume effect correction using a modified recovery coefficient approach based on functional volume and local contrast: physical validation and clinical feasibility in oncology.

BACKGROUND: 2-deoxy-2-[18F]fluoro-D-glucose 18F-FDG uptake within tumors reflects the glucose consumption of malignant tumors, i.e., the tumor activity. Thus, 18F-FDG uptake measurements enable improved therapeutic monitoring of patients in chemo- or radiotherapy treatment through the detection of changes in tumor uptake via quantitative measurements of the lesion standard uptake values (SUVs) or activity concentrations. A major bias that affects positron emission tomography (PET) image quantitation is the partial volume effect (PVE), which most strongly affects the smallest structures due to the poor spatial resolution of PET. Thus, PVE corrections are important when 18F-FDG-PET images are used as a quantitative tool for monitoring responses to therapy. The aim of this paper was to propose a PVE correction based on a modified recovery coefficient method (termed FARCAS) that considers the functional volumes and local contrasts of lesions that are automatically determined using a semi-automatic iterative segmentation algorithm. METHODS: The FARCAS method consists of establishing a set of calibration curves based on the mathematical fitting of the RC values as a function of the automatically determined functional lesion volume and local lesion contrast. We set up our method using data from a cylindrical phantom that included spheres of different volumes (range: 0.43 to 97.8 mL) and contrasts (range: 1.7 to 22.9), and we assessed the method using both cylindrical and anthropomorphic phantom data that also included spheres of different volumes and contrasts. FARCAS was also compared with conventional RC methods that only considered the lesion functional volume, either automatically determined (RCVa) or using the ground truth volume (RCVgt). Finally, the clinical feasibility of FARCAS and its evaluation on tumor classification were also assessed on 24 NSCLC lesions. RESULTS: Whatever the phantom considered, for the spheres with contrast <5, FARCAS obtained comparable results to RCVgt and better than RCVa. For the spheres with contrast >5, FARCAS and RCVa were not statistically different, neither for the cylindrical and nor the anthropomorphic phantom. For the cylindrical phantom FARCAS yielded corrections that were not statistically different to those of RCVa for the smallest spheres (V<2 mL), but statistically superior for the larger spheres (V≥2 mL). RCVgt maintained a non-statistically superior accuracy. Regarding the anthropomorphic data, FARCAS was statistically more accurate than RCVa but not RCVgt. As main findings regarding the clinical data, FARCAS modified the classifications of five of 24 NSCLC lesions based on quantitative PERCIST criteria. CONCLUSIONS: The PVE correction proposed in this paper allows the accurate quantification of the PVE-corrected SUV, allowing also an automatic definition of the Metabolic Target Volume (MTV). Our results revealed that the PVE correction based on FARCAS is a better approach than conventional RC to significantly reduce the impact of PVE on lesion quantification, thus improving the evaluation of tumor response to treatment based on PET-CT images.