Prognostic value of metabolic tumor volume on [(18)F]FDG PET/CT in addition to the TNM classification system of locally advanced non-small cell lung cancer.

Staging of non-small cell lung cancer (NSCLC) is commonly based on [18F]FDG PET/CT, in particular to exclude distant metastases and guide local therapy approaches like resection and radiotherapy. Although it is hoped that PET/CT will increase the value of primary staging compared to conventional imaging, it is generally limited to the characterization of TNM. The first aim of this study was to evaluate the PET parameter metabolic tumor volume (MTV) above liver background uptake as a prognostic marker in lung cancer. The second aim was to investigate the possibility of incorporating MTV into the TNM classification system for disease prognosis in locally advanced NSCLC treated with chemoradiotherapy. Retrospective evaluation of 235 patients with histologically proven, locally advanced NSCLC from the multi-centre randomized clinical PETPLAN trial and a clinical cohort from a hospital registry. The PET parameters SUVmax, SULpeak, MTV and TLG above liver background uptake were determined. Kaplan-Meier curves and stratified Cox proportional hazard regression models were used to investigate the prognostic value of PET parameters and TNM along with clinical variables. Subgroup analyses were performed to compare hazard ratios according to TNM, MTV, and the two variables combined. In the multivariable Cox regression analysis, MTV was associated with significantly worse overall survival independent of stage and other prognostic variables. In locally advanced disease stages treated with chemoradiotherapy, higher MTV was significantly associated with worse survival (median 17 vs. 32 months). Using simple cut-off values (45 ml for stage IIIa, 48 ml for stage IIIb, and 105 ml for stage IIIc), MTV was able to further predict differences in survival for stages IIIa-c. The combination of TNM and MTV staging system showed better discrimination for overall survival in locally advanced disease stages, compared to TNM alone. Higher metabolic tumor volume is significantly associated with worse overall survival and combined with TNM staging, it provides more precise information about the disease prognosis in locally advanced NSCLC treated with chemoradiotherapy compared to TNM alone. As a PET parameter with volumetric information, MTV represents a useful addition to TNM.

Brose A ，Miederer I ，König J ，Gkika E ，Sahlmann J ，Schimek-Jasch T ，Schreckenberger M ，Nestle U ，Kappes J ，Miederer M ... -  《-》

Clinico-pathological factors and [(18)F]FDG PET/CT metabolic parameters for prediction of progression-free survival in radioiodine refractory differentiated thyroid carcinoma.

Identifying prognostic markers for clinical outcomes is crucial in selecting appropriate treatment options for patients with radioiodine-refractory (RAI-R) differentiated thyroid carcinoma (DTC). The aim of this study was to investigate the prognostic value of clinico-pathological features and semiquantitative [18F]FDG PET/CT metabolic parameters in predicting progression-free survival (PFS) in DTC patients with RAI-R. This prospective cohort study included 110 consecutive RAI-R DTC patients who were referred for [18F]FDG PET/CT imaging. The lesion standard uptake values (SUV)s, including SUVmax, SUVmean, SULpeak as well astotal metabolic tumor volume (tMTV)and total lesion glycolysis (tTLG) were measured. Disease progression was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and/or Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) 1.0. PFS curves were plotted using Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses were performed to identify the prognostic factors for PFS. [18F]FDG PET/CT metabolic parameters demonstrate predictive value for PFS in RAI-R DTC patients, with sensitivity ranging from 70.7% to 81% and specificity from 75% to 92.3% (p < 0.001). PFS was significantly worse in patients with SUVmax > 6.39 g/ml, SUVmean > 3.68 g/ml, SULpeak > 3.14 g/ml, tTLG > 4.23 g/ml × cm3, and tMTV > 1.24 cm3. Clinico-pathological factors including age > 55, aggressive variant and follicular histological subtype, extra-thyroidal extension of the primary tumor, stage III - IV disease at initial DTC diagnosis, distant metastases detected on [18F]FDG PET/CT, and metabolic parameters of [18F]FDG PET/CT associated with PFS in univariate analysis (p < 0.01). In multivariate analysis, extra-thyroidal extension (HR: 2.25; 95% CI: 1.22 - 4.16; p = 0.01), distant metastases on [18F]FDG PET/CT (HR: 2.98; 95%CI: 1.62 - 5.5; p < 0.001), and tMTV > 1.24 cm3 (HR: 4.17; 95% CI: 2.02 - 8.6; p < 0.001), were independent prognostic factors for PFS. In addition to classic clinico-pathological factors, the semiquantitative [18F]FDG PET/CT metabolic parameters can be utilized for dynamic risk stratification for progression in RAI-R DTC patients. Furthermore, extra-thyroidal extension of the primary tumor, distant metastases, and tMTV > 1.24 cm3 are independent prognostic factors for PFS.

Phuong NT ，Son MH ，Thong MH ，Ha LN ... -  《BMC MEDICAL IMAGING》

Comparison of Two Modern Survival Prediction Tools, SORG-MLA and METSSS, in Patients With Symptomatic Long-bone Metastases Who Underwent Local Treatment With Surgery Followed by Radiotherapy and With Radiotherapy Alone.

Survival estimation for patients with symptomatic skeletal metastases ideally should be made before a type of local treatment has already been determined. Currently available survival prediction tools, however, were generated using data from patients treated either operatively or with local radiation alone, raising concerns about whether they would generalize well to all patients presenting for assessment. The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA), trained with institution-based data of surgically treated patients, and the Metastases location, Elderly, Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy model (METSSS), trained with registry-based data of patients treated with radiotherapy alone, are two of the most recently developed survival prediction models, but they have not been tested on patients whose local treatment strategy is not yet decided. (1) Which of these two survival prediction models performed better in a mixed cohort made up both of patients who received local treatment with surgery followed by radiotherapy and who had radiation alone for symptomatic bone metastases? (2) Which model performed better among patients whose local treatment consisted of only palliative radiotherapy? (3) Are laboratory values used by SORG-MLA, which are not included in METSSS, independently associated with survival after controlling for predictions made by METSSS? Between 2010 and 2018, we provided local treatment for 2113 adult patients with skeletal metastases in the extremities at an urban tertiary referral academic medical center using one of two strategies: (1) surgery followed by postoperative radiotherapy or (2) palliative radiotherapy alone. Every patient's survivorship status was ascertained either by their medical records or the national death registry from the Taiwanese National Health Insurance Administration. After applying a priori designated exclusion criteria, 91% (1920) were analyzed here. Among them, 48% (920) of the patients were female, and the median (IQR) age was 62 years (53 to 70 years). Lung was the most common primary tumor site (41% [782]), and 59% (1128) of patients had other skeletal metastases in addition to the treated lesion(s). In general, the indications for surgery were the presence of a complete pathologic fracture or an impending pathologic fracture, defined as having a Mirels score of ≥ 9, in patients with an American Society of Anesthesiologists (ASA) classification of less than or equal to IV and who were considered fit for surgery. The indications for radiotherapy were relief of pain, local tumor control, prevention of skeletal-related events, and any combination of the above. In all, 84% (1610) of the patients received palliative radiotherapy alone as local treatment for the target lesion(s), and 16% (310) underwent surgery followed by postoperative radiotherapy. Neither METSSS nor SORG-MLA was used at the point of care to aid clinical decision-making during the treatment period. Survival was retrospectively estimated by these two models to test their potential for providing survival probabilities. We first compared SORG to METSSS in the entire population. Then, we repeated the comparison in patients who received local treatment with palliative radiation alone. We assessed model performance by area under the receiver operating characteristic curve (AUROC), calibration analysis, Brier score, and decision curve analysis (DCA). The AUROC measures discrimination, which is the ability to distinguish patients with the event of interest (such as death at a particular time point) from those without. AUROC typically ranges from 0.5 to 1.0, with 0.5 indicating random guessing and 1.0 a perfect prediction, and in general, an AUROC of ≥ 0.7 indicates adequate discrimination for clinical use. Calibration refers to the agreement between the predicted outcomes (in this case, survival probabilities) and the actual outcomes, with a perfect calibration curve having an intercept of 0 and a slope of 1. A positive intercept indicates that the actual survival is generally underestimated by the prediction model, and a negative intercept suggests the opposite (overestimation). When comparing models, an intercept closer to 0 typically indicates better calibration. Calibration can also be summarized as log(O:E), the logarithm scale of the ratio of observed (O) to expected (E) survivors. A log(O:E) > 0 signals an underestimation (the observed survival is greater than the predicted survival); and a log(O:E) < 0 indicates the opposite (the observed survival is lower than the predicted survival). A model with a log(O:E) closer to 0 is generally considered better calibrated. The Brier score is the mean squared difference between the model predictions and the observed outcomes, and it ranges from 0 (best prediction) to 1 (worst prediction). The Brier score captures both discrimination and calibration, and it is considered a measure of overall model performance. In Brier score analysis, the "null model" assigns a predicted probability equal to the prevalence of the outcome and represents a model that adds no new information. A prediction model should achieve a Brier score at least lower than the null-model Brier score to be considered as useful. The DCA was developed as a method to determine whether using a model to inform treatment decisions would do more good than harm. It plots the net benefit of making decisions based on the model's predictions across all possible risk thresholds (or cost-to-benefit ratios) in relation to the two default strategies of treating all or no patients. The care provider can decide on an acceptable risk threshold for the proposed treatment in an individual and assess the corresponding net benefit to determine whether consulting with the model is superior to adopting the default strategies. Finally, we examined whether laboratory data, which were not included in the METSSS model, would have been independently associated with survival after controlling for the METSSS model's predictions by using the multivariable logistic and Cox proportional hazards regression analyses. Between the two models, only SORG-MLA achieved adequate discrimination (an AUROC of > 0.7) in the entire cohort (of patients treated operatively or with radiation alone) and in the subgroup of patients treated with palliative radiotherapy alone. SORG-MLA outperformed METSSS by a wide margin on discrimination, calibration, and Brier score analyses in not only the entire cohort but also the subgroup of patients whose local treatment consisted of radiotherapy alone. In both the entire cohort and the subgroup, DCA demonstrated that SORG-MLA provided more net benefit compared with the two default strategies (of treating all or no patients) and compared with METSSS when risk thresholds ranged from 0.2 to 0.9 at both 90 days and 1 year, indicating that using SORG-MLA as a decision-making aid was beneficial when a patient's individualized risk threshold for opting for treatment was 0.2 to 0.9. Higher albumin, lower alkaline phosphatase, lower calcium, higher hemoglobin, lower international normalized ratio, higher lymphocytes, lower neutrophils, lower neutrophil-to-lymphocyte ratio, lower platelet-to-lymphocyte ratio, higher sodium, and lower white blood cells were independently associated with better 1-year and overall survival after adjusting for the predictions made by METSSS. Based on these discoveries, clinicians might choose to consult SORG-MLA instead of METSSS for survival estimation in patients with long-bone metastases presenting for evaluation of local treatment. Basing a treatment decision on the predictions of SORG-MLA could be beneficial when a patient's individualized risk threshold for opting to undergo a particular treatment strategy ranged from 0.2 to 0.9. Future studies might investigate relevant laboratory items when constructing or refining a survival estimation model because these data demonstrated prognostic value independent of the predictions of the METSSS model, and future studies might also seek to keep these models up to date using data from diverse, contemporary patients undergoing both modern operative and nonoperative treatments. Level III, diagnostic study.

Lee CC ，Chen CW ，Yen HK ，Lin YP ，Lai CY ，Wang JL ，Groot OQ ，Janssen SJ ，Schwab JH ，Hsu FM ，Lin WH ... -  《-》

Primary Results of NRG-RTOG1106/ECOG-ACRIN 6697: A Randomized Phase II Trial of Individualized Adaptive (chemo)Radiotherapy Using Midtreatment (18)F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Stage III Non-Small Cell Lung Cance

Kong FS ，Hu C ，Pryma DA ，Duan F ，Matuszak M ，Xiao Y ，Ten Haken R ，Siegel MJ ，Hanna L ，Curran WJ ，Dunphy M ，Gelblum D ，Piert M ，Jolly S ，Robinson CG ，Quon A ，Loo BW ，Srinivas S ，Videtic GM ，Faria SL ，Ferguson C ，Dunlap NE ，Kundapur V ，Paulus R ，Siegel BA ，Bradley JD ，Machtay M ... -  《-》

Prognostic Role of Pretreatment Tumor Burden and Dissemination Features From 2-[(18)F]FDG PET/CT in Advanced Mantle Cell Lymphoma.

Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin lymphoma with poor prognosis. The usefulness of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) and its parameters in the evaluation of treatment response and prognosis is not yet clear. The aim of this study was to investigate the prognostic role of tumor burden and tumor dissemination features derived by 2-[18F]FDG PET/CT in advanced MCL. We retrospectively included 120 patients with advanced MCL who underwent baseline 2- 2-[18F]FDG PET/CT and end-of-treatment (eot) PET/CT. The baseline-PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value body weight (SUVbw), lean body mass (SUVlbm), body surface area (SUVbsa), metabolic tumor volume (MTV), total lesion glycolysis (TLG) and dissemination features (Dmax and Dmax-bsa). EotPET/CT was judged according to the Lugano classification. Progression-free survival (PFS) and overall survival (OS) were plotted according to the Kaplan-Meier method. At a median follow-up of 59 months, relapse/progression occurred in 68 patients while death in 38 patients with a median PFS and OS of 27.2 and 57.6 months, respectively. MIPI score, Bulky disease, Ki-67 index, metabolic response, pretreatment MTV and TLG were significantly associated with PFS at univariate analysis, but only metabolic response, MTV and TLG were confirmed to be independent prognostic factors. Considering OS, only dissemination features were demonstrated to be prognostic features. In conclusions, metabolic response and metabolic tumor burden parameters (MTV and TLG) are strongest predictor of PFS, while dissemination features may have a significant role for predicting OS.

Albano D ，Bianchetti N ，Talin A ，Dondi F ，Re A ，Tucci A ，Bertagna F ... -  《-》