The impact of the COVID-19 pandemic on oncological disease extent at FDG PET/CT staging: the ONCOVIPET study.

PURPOSE: To investigate whether the COVID-19 pandemic and national lockdown had an impact on the extent of cancer disease at FDG PET/CT staging as surrogate marker. METHODS: Retrospective observational study including cancer patients submitted to FDG PET/CT staging from June 1 to October 31, 2020, and June 1 to October 31, 2019, respectively. Data regarding primary tumour, nodal (N) status and number of involved nodal stations, and presence and number of distant metastases (M) were collected. Each scan was classified in limited vs advanced status. Data were aggregated across the study population and tumour type. Bi-weekly frequencies of the observed events were analysed. RESULTS: Six hundred eleven patients were included (240 in 2019 vs 371 in 2020, respectively). A significant increase of advanced disease patients (rate 1.56, P < 0.001), N + or M + patients (rate 1.84 and 2.09, respectively, P < 0.001), and patients with a greater number of involved N stations or M (rate 2.01 and 2.06, respectively, P < 0.001) were found in 2020 compared with data of 2019. Analysis by tumour type showed a significant increase of advanced disease in lymphoma and lung cancer in 2020 compared with 2019 (P < 0.001). In addition, a significant increase of nodal involvement was found in lung, gastro-intestinal, and breast cancers, as well as in lymphoma patients (P < 0.02). A significant increase of distant metastases was found in lung cancers (P = 0.002). CONCLUSION: Cancer patients with advanced disease at FDG PET/CT staging increased in 2020 compared with 2019, following the national lockdown due to the COVID-19 pandemic, 1.5-fold with a significant increase of patients with N or M involvement. Targeted health interventions are needed to mitigate the effects of the pandemic on patient outcome.

Short 2-[18F]Fluoro-2-Deoxy-D-Glucose PET Dynamic Acquisition Protocol to Evaluate the Influx Rate Constant by Regional Patlak Graphical Analysis in Patients With Non-Small-Cell Lung Cancer.

Purpose: To test a short 2-[18F]Fluoro-2-deoxy-D-glucose (2-[18F]FDG) PET dynamic acquisition protocol to calculate Ki using regional Patlak graphical analysis in patients with non-small-cell lung cancer (NSCLC). Methods: 24 patients with NSCLC who underwent standard dynamic 2-[18F]FDG acquisitions (60 min) were randomly divided into two groups. In group 1 (n = 10), a population-based image-derived input function (pIDIF) was built using a monoexponential trend (10-60 min), and a leave-one-out cross-validation (LOOCV) method was performed to validate the pIDIF model. In group 2 (n = 14), Ki was obtained by standard regional Patlak plot analysis using IDIF (0-60 min) and tissue response (10-60 min) curves from the volume of interests (VOIs) placed on descending thoracic aorta and tumor tissue, respectively. Moreover, with our method, the Patlak analysis was performed to obtain Ki,s using IDIFFitted curve obtained from PET counts (0-10 min) followed by monoexponential coefficients of pIDIF (10-60 min) and tissue response curve obtained from PET counts at 10 min and between 40 and 60 min, simulating two short dynamic acquisitions. Both IDIF and IDIFFitted curves were modeled to assume the value of 2-[18F]FDG plasma activity measured in the venous blood sampling performed at 45 min in each patient. Spearman's rank correlation, coefficient of determination, and Passing-Bablok regression were used for the comparison between Ki and Ki,s. Finally, Ki,s was obtained with our method in a separate group of patients (group 3, n = 8) that perform two short dynamic acquisitions. Results: Population-based image-derived input function (10-60 min) was modeled with a monoexponential curve with the following fitted parameters obtained in group 1: a = 9.684, b = 16.410, and c = 0.068 min-1. The LOOCV error was 0.4%. In patients of group 2, the mean values of Ki and Ki,s were 0.0442 ± 0.0302 and 0.33 ± 0.0298, respectively (R 2 = 0.9970). The Passing-Bablok regression for comparison between Ki and Ki,s showed a slope of 0.992 (95% CI: 0.94-1.06) and intercept value of -0.0003 (95% CI: -0.0033-0.0011). Conclusions: Despite several practical limitations, like the need to position the patient twice and to perform two CT scans, our method contemplates two short 2-[18F]FDG dynamic acquisitions, a population-based input function model, and a late venous blood sample to obtain robust and personalized input function and tissue response curves and to provide reliable regional Ki estimation.

Dynamic 11C-Methionine PET-CT: Prognostic Factors for Disease Progression and Survival in Patients with Suspected Glioma Recurrence.

PURPOSE: The prognostic evaluation of glioma recurrence patients is important in the therapeutic management. We investigated the prognostic value of 11C-methionine PET-CT (MET-PET) dynamic and semiquantitative parameters in patients with suspected glioma recurrence. METHODS: Sixty-seven consecutive patients who underwent MET-PET for suspected glioma recurrence at MR were retrospectively included. Twenty-one patients underwent static MET-PET; 46/67 underwent dynamic MET-PET. In all patients, SUVmax, SUVmean and tumour-to-background ratio (T/B) were calculated. From dynamic acquisition, the shape and slope of time-activity curves, time-to-peak and its SUVmax (SUVmaxTTP) were extrapolated. The prognostic value of PET parameters on progression-free (PFS) and overall survival (OS) was evaluated using Kaplan-Meier survival estimates and Cox regression. RESULTS: The overall median follow-up was 19 months from MET-PET. Recurrence patients (38/67) had higher SUVmax (p = 0.001), SUVmean (p = 0.002) and T/B (p < 0.001); deceased patients (16/67) showed higher SUVmax (p = 0.03), SUVmean (p = 0.03) and T/B (p = 0.006). All static parameters were associated with PFS (all p < 0.001); T/B was associated with OS (p = 0.031). Regarding kinetic analyses, recurrence (27/46) and deceased (14/46) patients had higher SUVmaxTTP (p = 0.02, p = 0.01, respectively). SUVmaxTTP was the only dynamic parameter associated with PFS (p = 0.02) and OS (p = 0.006). At univariate analysis, SUVmax, SUVmean, T/B and SUVmaxTTP were predictive for PFS (all p < 0.05); SUVmaxTTP was predictive for OS (p = 0.02). At multivariate analysis, SUVmaxTTP remained significant for PFS (p = 0.03). CONCLUSION: Semiquantitative parameters and SUVmaxTTP were associated with clinical outcomes in patients with suspected glioma recurrence. Dynamic PET-CT acquisition, with static and kinetic parameters, can be a valuable non-invasive prognostic marker, identifying patients with worse prognosis who require personalised therapy.

Cavernous Hemangioma: A Potential Pitfall at Delayed 18F-FDG PET/CT Scan.

ABSTRACT: We report the case of a 72-year-old woman who underwent neoadjuvant chemotherapy, right quadrantectomy (invasive ductal carcinoma, G3, pT2pN1pMx), and adjuvant radiotherapy. Two years later, a follow-up CT revealed a hepatic nodule of approximately 1 cm suspected for metastasis. 18F-FDG PET/CT was performed for restaging. Standard total-body 18F-FDG PET/CT acquisition showed no abnormal 18F-FDG uptake in the hepatic nodule. A delayed 18F-FDG PET/CT acquisition of upper abdomen was performed at 180 minutes postradiopharmaceutical injection and showed increased 18F-FDG uptake in the hepatic nodule. After nodule resection, the histological examination proved a cavernous hemangioma.

Application of Artificial Neural Network to Preoperative 18F-FDG PET/CT for Predicting Pathological Nodal Involvement in Non-small-cell Lung Cancer Patients.

Purpose: To evaluate the performance of artificial neural networks (aNN) applied to preoperative 18F-FDG PET/CT for predicting nodal involvement in non-small-cell lung cancer (NSCLC) patients. Methods: We retrospectively analyzed data from 540 clinically resectable NSCLC patients (333 M; 67.4 ± 9 years) undergone preoperative 18F-FDG PET/CT and pulmonary resection with hilo-mediastinal lymphadenectomy. A 3-layers NN model was applied (dataset randomly splitted into 2/3 training and 1/3 testing). Using histopathological reference standard, NN performance for nodal involvement (N0/N+ patient) was calculated by ROC analysis in terms of: area under the curve (AUC), accuracy (ACC), sensitivity (SE), specificity (SP), positive and negative predictive values (PPV, NPV). Diagnostic performance of PET visual analysis (N+ patient: at least one node with uptake ≥ mediastinal blood-pool) and of logistic regression (LR) was evaluated. Results: Histology proved 108/540 (20%) nodal-metastatic patients. Among all collected data, relevant features selected as input parameters were: patients' age, tumor parameters (size, PET visual and semiquantitative features, histotype, grading), PET visual nodal result (patient-based, as N0/N+ and N0/N1/N2). Training and testing NN performance (AUC = 0.849, 0.769): ACC = 80 and 77%; SE = 72 and 58%; SP = 81 and 81%; PPV = 50 and 44%; NPV = 92 and 89%, respectively. Visual PET performance: ACC = 82%, SE = 32%, SP = 94%; PPV = 57%, NPV = 85%. Training and testing LR performance (AUC = 0.795, 0.763): ACC = 75 and 77%; SE = 68 and 55%; SP = 77 and 82%; PPV = 43 and 43%; NPV = 90 and 88%, respectively. Conclusions: aNN application to preoperative 18F-FDG PET/CT provides overall good performance for predicting nodal involvement in NSCLC patients candidate to surgery, especially for ruling out nodal metastases, being NPV the best diagnostic result; a high NPV was also reached by PET qualitative assessment. Moreover, in such population with low a priori nodal involvement probability, aNN better identify the relatively few and unexpected nodal-metastatic patients than PET analysis, so supporting the additional aNN use in case of PET-negative images.

The Prognostic Value of 18F-FDG PET Imaging at Staging in Patients with Malignant Pleural Mesothelioma: A Literature Review.

Malignant pleural mesothelioma (MPM) is an aggressive malignancy, frequently diagnosed at locally-advanced/metastatic stages. Due to a very poor prognosis and limited treatment options, the need to identify new prognostic markers represents a great clinical challenge. The prognostic role of metabolic information derived from Positron Emission Tomography (PET) with 18F-Fluoro-deoxy-glucose (18F-FDG) has been investigated in different MPM settings, however with no definitive consensus. In this comprehensive review, the prognostic value of FDG-PET imaging exclusively performed at staging in MPM patients was evaluated, conducting a literature search on PubMed/MEDLINE from 2010 to 2020. From the 19 selected studies, despite heterogeneity in several aspects, staging FDG-PET imaging emerges as a valuable prognostic biomarker, with higher tumor uptake predictive of worse prognosis, and with volumetric metabolic parameters like Metabolic Tumor Volume, (MTV) and Total Lesion Glycolisis (TLG) performing better than SUVmax. However, PET uptake parameters were not always confirmed as independent prognostic factors, especially in patients previously treated with pleurodesis and with a non-epithelioid histotype. Future prospective studies in larger and clinically homogeneous populations, and using more standardized methods of PET images analysis, are needed to further validate the value of staging FDG-PET in the prognostic MPM stratification, with a potential impact on better patient-tailored treatment planning, in the perspective of personalized medicine.

18F-FDG and 68Ga-DOTATOC PET/CT Findings in a Case of Abdominal Leiomyosarcoma.

ABSTRACT: We report the case of a 58-year-old man with mesenteric nodule at CT performed for abdominal pain. In the suspicion of neoplastic disease, he underwent 18F-FDG PET/CT that did not show abnormal uptake. The nodule was monitored alternating CT and MRI. Two years after the first detection, MRI revealed an increase in size, and 18F-FDG PET/CT was repeated for metabolic evaluation, showing increased metabolic activity. In suspicion of neuroendocrine tumor, for anatomical site, slow growth, and clinical symptoms, 68Ga-DOTATOC PET/CT was performed showing focal uptake, indicating high expression of somatostatin receptors. The final pathology report was consistent with high-grade leiomyosarcoma.

A Bio-Imaging Signature as a Predictor of Clinical Outcomes in Locally Advanced Pancreatic Cancer.

Purpose: To evaluate the predictive value of 18F-FDG PET/CT semiquantitative parameters of the primary tumour and CA 19-9 levels assessed before treatment in patients with locally advanced pancreatic cancer (LAPC). Methods: Among one-hundred twenty patients with LAPC treated at our institution with initial chemotherapy followed by curative chemoradiotherapy (CRT) from July 2013 to January 2019, a secondary analysis with baseline 18F-FDG PET/CT was conducted in fifty-eight patients. Pre-treatment CA 19-9 level and the maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of primary tumour were measured. The receiving operating characteristics (ROC) analysis was performed to define the cut-off point of SUVmax, MTV, TLG and CA 19-9 values to use in prediction of early progression (EP), local progression (LP) and overall survival (OS). Areas under the curve (AUCs) were assessed for all variables. Post-test probability was calculated to evaluate the advantage for parameters combination. Results: For EP, CA 19-9 level > 698 U/mL resulted the best marker to identify patient at higher risk with OR of 5.96 (95% CI, 1.66-19.47; p = 0.005) and a Positive Predictive Value (PPV) of 61%. For LP, the most significant parameter was TLG (OR 9.75, 95% CI, 1.64-57.87, p = 0.012), with PPV of 83%. For OS, the most significant parameter was MTV (OR 3.12, 95% CI, 0.9-10.83, p = 0.07) with PPV of 88%. Adding consecutively each of the other parameters, PPV to identify patients at risk resulted further increased (>90%). Conclusions: Pre-treatment CA 19-9 level, as well as MTV and TLG values of primary tumour at baseline 18F-FDG PET/CT and their combination, may represent significant predictors of EP, LP and OS in LAPC patients.

Is 18F-fluorodeoxyglucose positron emission tomography/computed tomography useful to discriminate metachronous lung cancer from metastasis in patients with oncological history?

BACKGROUND: Solitary pulmonary nodules detected during follow-up in patients with previous cancer history have a high probability of malignancy being either a metachronous lung cancer or a metastasis. This distinction represents a crucial issue in the perspective of "personalized medicine," implying different treatments and prognosis. Aim, to evaluate the role of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in distinguishing whether solitary pulmonary nodules are metachronous cancers or metastases and the relationship between the nodule's characteristics and their nature. METHODS: From a single-institution database, we retrospectively selected all patients with a previous cancer history who performed 18F-FDG PET/CT to evaluate pulmonary nodules detected during follow-up, ranging from 5 mm to 40 mm, and histologically diagnosed as malignant. RESULTS: Between September 2009 and August 2017, 127 patients (80 males; mean age=70.2±8.5years) with 127 malignant nodules were included: 103/127 (81%) metachronous cancers, 24/127 (19%) metastases. In both groups, PET/CT provided good and equivalent detection rate of malignancy (81% vs. 83%). No differences between metachronous cancers and metastases were found in: patient's age (70.3±8.1 years vs. 69.5±9.7years), gender (males=63.1% vs. 62.5%), interval between previous cancer diagnosis and nodules' detection (median time=4years vs. 4.5years), location (right-lung=55% vs. 54%; upper-lobes=64% vs. 67%; central-site=31% vs. 25%), size (median size=17mm vs. 19.5mm), 18F-FDG standardized uptake value (median SUVmax=5.2 vs. 5.9). CONCLUSIONS: In oncological patients, despite its high detection rate, 18F-FDG PET/CT, as well as any other clinico-anatomical features, cannot distinguish whether a malignant solitary pulmonary nodule is a metachronous lung cancer or a metastasis, supporting the need of histological differential diagnosis.

18F-FDG PET/CT diagnostic performance in solitary and multiple pulmonary nodules detected in patients with previous cancer history: reports of 182 nodules.

PURPOSE: In oncological patients, 18F-FDG PET/CT performance for pulmonary nodules' characterization is not well-established. Thus, the purpose of this study was to evaluate the 18F-FDG PET/CT diagnostic performance in pulmonary nodules detected during follow-up in oncological patients and the relationship between malignancy and nodules' characteristics. METHODS: We retrospectively evaluated 182 pulmonary nodules (121 solitary, 61 multiple; mean size = 16.5 ± 8.1 mm, mean SUVmax = 5.2 ± 5.1) in 148 oncological patients (89 males; mean age = 69.5 ± 8.4 years). Final diagnosis was established by histology or radiological follow-up. Diagnostic performance of 18F-FDG visual analysis (malignancy-criterion: uptake ≥ mediastinal activity), ROC curve analysis for SUVmax and nodules' characteristics were assessed. RESULTS: In 182 nodules, the prevalence of malignancy was 75.8%; PET/CT provided sensitivity = 79%, specificity = 81.8%, accuracy = 79.7%, PPV = 93.1%, NPV = 55.4%; ROC analysis (SUVmax cut-off = 1.7) provided sensitivity = 85.5%, specificity = 72.7%. In 121 solitary nodules, the prevalence of malignancy was 87.6%; PET/CT provided sensitivity = 82.1%, specificity = 73.3%, accuracy = 81%, PPV = 95.6%, NPV = 36.7%; ROC analysis (SUVmax cut-off = 2) provided sensitivity = 84%, specificity = 80%. In 61 multiple nodules, the prevalence of malignancy was 52.5%; PET/CT (nodule and patient-based analysis, respectively) provided sensitivity = 68.7% and 88.9%, specificity = 86.2% and 55.6%, accuracy = 77% and 77.8%, PPV = 84.4% and 80%, NPV = 71.8% and 71.5%; ROC analysis (nodule-based, SUVmax cut-off = 1.8) provided sensitivity = 71.9%, specificity = 82.8%. Malignant nodules were prevalent in males, in solitary pattern and in upper lobes, and had significantly greater size and metabolic activity (SUVmax and TLG) than benign ones, with no differences in interval-time between previous cancer diagnosis and nodule detection, patients' age or other nodules' features (lung side, central/peripheral). When comparing solitary and multiple patterns, malignant nodules had significantly greater size and metabolic activity than benign ones in both groups. CONCLUSIONS: In oncological patients, 18F-FDG PET/CT provides good diagnostic performance for ruling in the malignancy in pulmonary nodules detected during follow-up, even at small size and especially when solitary. In multiple patterns, PET seems useful in the perspective of a personalized management, for identifying the "reference" nodule deserving histological assessment.

Response evaluation with 18F-FDG PET/CT in metastatic breast cancer patients treated with Palbociclib: first experience in clinical practice.

OBJECTIVE: Palbociclib is a cyclin-dependent kinase 4/6 inhibitor recently approved for treatment in advanced or metastatic breast cancer (BC) patients. The use of 18F-FDG PET/CT for chemo/endocrine therapy response assessment in BC patients is well reported in the literature, but no studies have evaluated its role for assessing Palbociclib efficacy in clinical practice. Our study aimed to evaluate the potential role of 18F-FDG PET/CT in this setting. METHODS: In 12 metastatic BC patients (mean age = 62 ± 10 years) treated with Palbociclib plus endocrine therapy and who underwent a baseline and post-therapy 18F-FDG PET/CT, we retrospectively compared the Metabolic Response Evaluation (MRE, based on PET/CT) to the Standard Response Evaluation (SRE, based on clinico-laboratory and morphological data); we also assessed the influence of additional PET/CT information on the patients' management. RESULTS: Compared to SRE, MRE increased the proportion of patients classified with progressive disease from 25 to 50% and differed from SRE in 8/12 patients: 3/8 shifted from stable disease or undetermined response to metabolic progression (more unfavorable category), 4/8 from stable disease to partial or complete metabolic response, and 1/8 from partial response to complete metabolic response (more favorable category). Additional PET/CT information led to a change in patients' management in 3/12 (25%) patients. CONCLUSION: In BC patients treated with Palbociclib, additional 18F-FDG PET/CT information seems clinically useful, with respect to personalized management, to early intercept patients who should discontinue Palbociclib because of progressive disease and to select patients requiring a strict monitoring of additional metabolic findings. Further studies are needed to confirm these preliminary results.

The kinetics of 18F-FDG in lung cancer: compartmental models and voxel analysis.

BACKGROUND: The validation of the most appropriate compartmental model that describes the kinetics of a specific tracer within a specific tissue is mandatory before estimating quantitative parameters, since the behaviour of a tracer can be different among organs and diseases, as well as between primary tumours and metastases. The aims of our study were to assess which compartmental model better describes the kinetics of 18F-Fluorodeoxygluxose(18F-FDG) in primary lung cancers and in metastatic lymph nodes; to evaluate whether quantitative parameters, estimated using different innovative technologies, are different between lung cancers and lymph nodes; and to evaluate the intra-tumour inhomogeneity. RESULTS: Twenty-one patients (7 females; 71 ± 9.4 years) with histologically proved lung cancer, prospectively evaluated, underwent 18F-FDG PET-CT for staging. Spectral analysis iterative filter (SAIF) method was used to design the most appropriate compartmental model. Among the compartmental models arranged using the number of compartments suggested by SAIF results, the best one was selected according to Akaike information criterion (AIC). Quantitative analysis was performed at the voxel level. K1, Vb and Ki were estimated with three advanced methods: SAIF approach, Patlak analysis and the selected compartmental model. Pearson's correlation and non-parametric tests were used for statistics. SAIF showed three possible irreversible compartmental models: Tr-1R, Tr-2R and Tr-3R. According to well-known 18F-FDG physiology, the structure of the compartmental models was supposed to be catenary. AIC indicated the Sokoloff's compartmental model (3K) as the best one. Excellent correlation was found between Ki estimated by Patlak and by SAIF (R2 = 0.97, R2 = 0.94, at the global and the voxel level respectively), and between Ki estimated by 3K and by SAIF (R2 = 0.98, R2 = 0.95, at the global and the voxel level respectively). Using the 3K model, the lymph nodes showed higher mean and standard deviation of Vb than lung cancers (p < 0.0014, p < 0.0001 respectively) and higher standard deviation of K1 (p < 0.005). CONCLUSIONS: One-tissue reversible plus one-tissue irreversible compartmental model better describes the kinetics of 18F-FDG in lung cancers, metastatic lymph nodes and normal lung tissues. Quantitative parameters, estimated at the voxel level applying different advanced approaches, show the inhomogeneity of neoplastic tissues. Differences in metabolic activity and in vascularization, highlighted among all cancers and within each individual cancer, confirm the wide variability in lung cancers and metastatic lymph nodes. These findings support the need of a personalization of therapeutic approaches.

The predictive value of 18F-FDG PET-CT for assessing the clinical outcomes in locally advanced NSCLC patients after a new induction treatment: low-dose fractionated radiotherapy with concurrent chemotherapy.

BACKGROUND: Patients with locally advanced non-small-cell lung cancer (LA-NSCLC) have poor prognosis despite several multimodal approaches. Recently, low-dose fractionated radiotherapy concurrent to the induction chemotherapy (IC-LDRT) has been proposed to further improve the effects of chemotherapy and prognosis. Until now, the predictive value of metabolic response after IC-LDRT has not yet been investigated. AIM: to evaluate whether the early metabolic response, assessed by 18F-fluoro-deoxyglucose positron emission-computed tomography (18F-FDG PET-CT), could predict the prognosis in LA-NSCLC patients treated with a multimodal approach, including IC-LDRT. METHODS: Forty-four consecutive patients (35males, mean age: 66 ± 7.8 years) with stage IIIA/IIIB NSCLC were retrospectively evaluated. Forty-four patients underwent IC-LDRT (2 cycles of chemotherapy, 40 cGy twice daily), 26/44 neo-adjuvant chemo-radiotherapy (CCRT: 50.4Gy), and 20/44 surgery. 18F-FDG PET-CT was performed before (baseline), after IC-LDRT (early) and after CCRT (final), applying PET response criteria in solid tumours (PERCIST). Patients with complete/partial metabolic response were classified as responders; patients with stable/progressive disease as non-responders. Progression free survival (PFS) and overall survival (OS) were assessed using Kaplan-Meyer analysis; the relationship between clinical factors and survivals were assessed using uni-multivariate regression analysis. RESULTS: Forty-four out of 44, 42/44 and 23/42 patients underwent baseline, early and final PET-CT, respectively. SULpeak of primary tumour and lymph-node significantly (p = 0.004, p = 0.0002, respectively) decreased after IC-LDRT with a further reduction after CCRT (p = 0.0006, p = 0.02, respectively). At early PET-CT, 20/42 (47.6%) patients were classified as responders, 22/42 (52.3%) as non-responders. At final PET-CT, 19/23 patients were classified as responders (12 responders and 7 non-responders at early PET-CT), and 4/23 as non-responders (all non-responders at early PET-CT). Early responders had better PFS and OS than early non-responders (p ≤ 0.01). Early metabolic response was predictive factor for loco-regional, distant and global PFS (p = 0.02, p = 0.01, p = 0.005, respectively); surgery for loco-regional and global PFS (p = 0.03, p = 0.009, respectively). CONCLUSIONS: In LA-NSCLC patients, 18F-FDG metabolic response assessed after only two cycles of IC-LDRT predicts the prognosis. The early evaluation of metabolic changes could allow to personalize therapy. This multimodality approach, including both low-dose radiotherapy that increases the effects of induction chemotherapy, and surgery that removes the disease, improved clinical outcomes. Further prospective investigation of this new induction approach is warranted.