[18 F]-FDG PET radiomic model as prognostic biomarker in diffuse large B-cell lymphoma.

To evaluate the association between radiomic features (RFs) extracted from 18 F-FDG PET/CT (18 F-FDG-PET) with progression-free survival (PFS) and overall survival (OS) in diffuse large-B-cell lymphoma (DLBCL) patients eligible to first-line chemotherapy. DLBCL patients who underwent 18 F-FDG-PET prior to first-line chemotherapy were retrospectively analyzed. RFs were extracted from the lesion showing the highest uptake. A radiomic score to predict PFS and OS was obtained by multivariable Elastic Net Cox model. Radiomic univariate model, clinical and combined clinical-radiomic multivariable models to predict PFS and OS were obtained. 112 patients were analyzed. Median follow-up was 34.7 months (Inter-Quartile Range (IQR) 11.3-66.3 months) for PFS and 41.1 (IQR 18.4-68.9) for OS. Radiomic score resulted associated with PFS and OS (p < 0.001), outperforming conventional PET parameters. C-index (95% CI) for PFS prediction were 0.67 (0.58-0.76), 0.81 (0.75-0.88) and 0.84 (0.77-0.91) for clinical, radiomic and combined clinical-radiomic model, respectively. C-index for OS were 0.77 (0.66-0.89), 0.84 (0.76-0.91) and 0.90 (0.81-0.98). In the Kaplan-Meier analysis (low-IPI vs. high-IPI), the radiomic score was significant predictor of PFS (p < 0.001). The radiomic score was an independent prognostic biomarker of survival in DLBCL patients. The extraction of RFs from baseline 18 F-FDG-PET might be proposed in DLBCL to stratify high-risk versus low-risk patients of relapse after first-line therapy, especially in low-IPI patients.

First Live-Experience Session with PET/CT Specimen Imager: A Pilot Analysis in Prostate Cancer and Neuroendocrine Tumor.

OBJECTIVE: to evaluate the feasibility of the intra-operative application of a specimen PET/CT imager in a clinical setting. MATERIALS AND METHODS: this is a pilot analysis performed in three patients who received an intra-operative administration of 68Ga-PSMA-11 (n = 2) and 68Ga-DOTA-TOC (n = 1), respectively. Patients were administrated with PET radiopharmaceuticals to perform radio-guided surgery with a beta-probe detector during radical prostatectomy for prostate cancer (PCa) and salvage lymphadenectomy for recurrent neuroendocrine tumor (NET) of the ileum, respectively. All procedures have been performed within two ongoing clinical trials in our Institute (NCT05596851 and NCT05448157). Pathologic assessment with immunohistochemistry (PSMA-staining and SSA immunoreactivity) was considered as standard of truth. Specimen images were compared with baseline PET/CT images and histopathological analysis. RESULTS: Patients received 1 MBq/Kg of 68Ga-PSMA-11 (PCa) or 1.2 MBq/Kg of 68Ga-DOTA-TOC (NET) prior to surgery. Specimens were collected, positioned in the dedicated specimen container, and scanned to obtain high-resolution PET/CT images. In all cases, a perfect match was observed between the findings detected by the specimen imager and histopathology. Overall, the PET spatial resolution was sensibly higher for the specimen images compared to the baseline whole-body PET/CT images. Furthermore, the use of the PET/CT specimen imager did not significantly interfere with any procedures, and the overall length of the surgery was not affected using the PET/CT specimen imager. Finally, the radiation exposure of the operating theater staff was lower than 40 µSv per procedure (range 26-40 µSv). CONCLUSIONS: the image acquisition of specimens obtained by patients who received intra-surgery injections of 68Ga-PSMA-11 and 68Ga-DOTA-TOC was feasible and reliable also in a live-experience session and has been easily adapted to surgery daily practice. The high sensitivity, together with the evaluation of intra-lesion tumor heterogeneity, were the most relevant results since the data derived from specimen PET/CT imaging matched perfectly with the histopathological analysis.

[18F]FDG PET/CT: Lung Nodule Evaluation in Patients Affected by Renal Cell Carcinoma.

Renal Cell Carcinoma (RCC) is generally characterized by low-FDG avidity, and [18F]FDG-PET/CT is not recommended to stage the primary tumor. However, its role to assess metastases is still unclear. The aim of this study was to evaluate the diagnostic accuracy of [18F]FDG-PET/CT in correctly identifying RCC lung metastases using histology as the standard of truth. The records of 350 patients affected by RCC were retrospectively analyzed. The inclusion criteria were: (a) biopsy- or histologically proven RCC; (b) Computed Tomography (CT) evidence of at least one lung nodule; (c) [18F]FDG-PET/CT performed prior to lung surgery; (d) lung surgery with histological analysis of surgical specimens; (e) complete follow-up available. A per-lesion analysis was performed, and diagnostic accuracy was reported as sensitivity and specificity, using histology as the standard of truth. [18F]FDG-PET/CT semiquantitative parameters (Standardized Uptake Value [SUVmax], Metabolic Tumor Volume [MTV] and Total Lesion Glycolysis [TLG]) were collected for each lesion. Sixty-seven patients with a total of 107 lesions were included: lung metastases from RCC were detected in 57 cases (53.3%), while 50 lesions (46.7%) were related to other lung malignancies. Applying a cut-off of SUVmax ≥ 2, the sensitivity and the specificity of [18F]FDG-PET/CT in detecting RCC lung metastases were 33.3% (95% CI: 21.4-47.1%) and 26% (95%CI: 14.6-40.3%), respectively. Although the analysis demonstrated a suboptimal diagnostic accuracy of [18F]FDG-PET/CT in discriminating between lung metastases from RCC and other malignancies, a semiquantitative analysis that also includes volumetric parameters (MTV and TLG) could support the correct interpretation of [18F]FDG-PET/CT images.

Gene expression profiling and FDG-PET radiomics uncover radiometabolic signatures associated with outcome in DLBCL.

Emerging evidence indicates that chemoresistance is closely related to altered metabolism in cancer. Here, we hypothesized that distinct metabolic gene expression profiling (GEP) signatures might be correlated with outcome and with specific fluorodeoxyglucose positron emission tomography (FDG-PET) radiomic profiles in diffuse large B-cell lymphoma (DLBCL). We retrospectively analyzed a discovery cohort of 48 consecutive patients with DLBCL treated at our center with standard first-line chemoimmunotherapy by performing targeted GEP (T-GEP)- and FDG-PET radiomic analyses on the same target lesions at baseline. T-GEP-based metabolic profiling identified a 6-gene signature independently associated with outcomes in univariate and multivariate analyses. This signature included genes regulating mitochondrial oxidative metabolism (SCL25A1, PDK4, PDPR) that were upregulated and was inversely associated with genes involved in hypoxia and glycolysis (MAP2K1, HIF1A, GBE1) that were downregulated. These data were validated in 2 large publicly available cohorts. By integrating FDG-PET radiomics and T-GEP, we identified a radiometabolic signature (RadSig) including 4 radiomic features (histo kurtosis, histo energy, shape sphericity, and neighboring gray level dependence matrix contrast), significantly associated with the metabolic GEP-based signature (r = 0.43, P = .0027) and with progression-free survival (P = .028). These results were confirmed using different target lesions, an alternative segmentation method, and were validated in an independent cohort of 64 patients. RadSig retained independent prognostic value in relation to the International Prognostic Index score and metabolic tumor volume (MTV). Integration of RadSig and MTV further refined prognostic stratification. This study provides the proof of principle for the use of FDG-PET radiomics as a tool for noninvasive assessment of cancer metabolism and prognostic stratification in DLBCL.

Predictors of positive axillary non-sentinel lymph nodes in breast cancer patients with positive sentinel lymph node biopsy after neoadjuvant systemic therapy.

AIM: To assess the rate of positive non-sentinel lymph nodes (non-SLNs) after neoadjuvant systemic therapy (NAST) in breast cancer (BC) following positive sentinel lymph node biopsy (SLNB). MATERIALS AND METHODS: From institutional database, 265 consecutive patients receiving NAST for cT1-3, any N, M0 BC between 2001 and 2018 were identified. Patients presented clinically negative axilla before surgery and were candidate for SLNB. Following metastatic SLNB, completion axillary lymph node dissection (AxLND) was performed. Non-SLNs rate was investigated using multivariate (MV) logistic regression models. The distribution of non-SLNs across the axilla was observed. RESULTS: Positive non-SLNs were found in 62.3% of cases and showed no correlation with SLN metastasis size. At MV, statistically significant variables associated with non-SLNs were older age (p = 0.025), clinically positive lymph nodes (p = 0.002), SLN extracapsular extension (ECE, p = 0.001), and higher ratio of positive SLNs/total SLNs (p = 0.016). ECE and higher nodal ratio were independent predictors of III axillary level positivity. By categorizing patients in intermediate- and high-risk groups using the study variables, positive non-SLNs were found in the range of 23-56% across the three axillary levels, rates which did not support radiotherapy volume de-escalation. The III axillary level lower involvement (6.3%) was better identified with the RAPCHEM trial criteria based on the ypN status after AxLND. CONCLUSIONS: Involved non-SLNs rate following positive SLNB after NAST is nearly double the rate observed after primary surgery, supporting some intervention on the axilla. If AxLND is limited to I and II level, the involvement of the III level up to 31% of the cases seems to require some additional treatment, while the omission in selected cases needs further investigation.

From the Magic Bullet to Theragnostics: Certitudes and Hypotheses, Trying to Optimize the Somatostatin Model.

The first "theragnostic model", that of radioiodine, was first applied both in diagnosis and therapy in the 1940s. Since then, many other theragnostic models have been introduced into clinical practice. To bring about the closest pharmacokinetic connection, the radiocompound used for diagnosis and therapy should be the same, although at present this is rarely applicable. Today, a widely applied and effective model is also the "DOTA-Ga-68/Lu-177", used with success in neuroendocrine tumors (NET). In this paper, we analyze the necessary steps from the in vitro evaluation of a target to the choice of radionuclide and chelate for therapy up to in vivo transition and clinical application of most employed radiocompounds used for theragnostic purposes. Possible future applications and strategies of theragnostic models are also highlighted.

18F-FDG PET/CT in asymptomatic patients with COVID-19: the submerged iceberg surfaces.

OBJECTIVE: The aim of this case series is to describe our experience in diagnosis and management of oncological asymptomatic patients with COVID-19 who underwent 18F-FDG PET/CT. METHODS: From March 9 to March 31, 2020, we identified 5 patients who had PET/CT findings suspicious for COVID-19, but no symptom of infection. RESULTS: The first three patients were administered an SARS-CoV-2 test in a COVID-dedicated center, while the fourth and fifth were tested in our institution, in accordance with a new internal procedure. The SARS-CoV-2 test yielded positive results in all five patients. CONCLUSION: In this COVID-19 emergency, our task as radiologists and nuclear medicine physicians is to be able to identify imaging findings suggestive of the disease and to manage patients without overloading the hospital system.

Interim 18F-FDG-PET/CT during chemo-radiotherapy in the management of oesophageal cancer patients. A systematic review.

Oesophageal cancer is an aggressive disease. The possibility to early stratify patients as responsive and non-responsive with a non-invasive method is extremely appealing. The uptake of Fluorodeoxyglucose (18F-FDG) in tumours, provided by positron emission tomography (PET) images, has been proved to be useful to assess the initial staging of the disease, recurrence, and response to chemotherapy and chemo-radiotherapy (CRT). In the last years, efforts have been focused on the possibility to use ad interim 18F-FDG-PET/CT (PETint) to evaluate response during radiation therapy. However, controversial findings have been reported, although some relevant results would support its use for individual therapeutic decision. The present review assembles the comprehensive literature of the last decade to evaluate whether and in which cases PETint may offer predictive potential in oesophageal cancer. All the analysed studies (13 studies, 697 patients) denoted PETint as a challenging examination for early assessment of outcomes during CRT. In particular, 8 studies advocated the predictivity of PETint, whilst 5 did not find any correlation between the interim variation of PET parameters and the pathological complete response and/or the clinical outcome. The reasons that possibly have caused contradictions among the studies demand further research with prospective and uniform protocols and methods of analysis to assess the predictive and prognostic value of PETint in oesophageal cancer.

Role of interim 18F-FDG-PET/CT for the early prediction of clinical outcomes of Non-Small Cell Lung Cancer (NSCLC) during radiotherapy or chemo-radiotherapy. A systematic review.

BACKGROUND: Non-Small Cell Lung Cancer (NSCLC) is characterized by aggressiveness and includes the majority of thorax malignancies. The possibility of early stratification of patients as responsive and non-responsive to radiotherapy with a non-invasive method is extremely appealing. The distribution of the Fluorodeoxyglucose (18F-FDG) in tumours, provided by Positron-Emission-Tomography (PET) images, has been proved to be useful to assess the initial staging of the disease, recurrence, and response to chemotherapy and chemo-radiotherapy (CRT). OBJECTIVES: In the last years, particular efforts have been focused on the possibility of using ad interim 18F-FDG PET (FDGint) to evaluate response already in the course of radiotherapy. However, controversial findings have been reported for various malignancies, although several results would support the use of FDGint for individual therapeutic decisions, at least in some pathologies. The objective of the present review is to assemble comprehensively the literature concerning NSCLC, to evaluate where and whether FDGint may offer predictive potential. METHODS: Several searches were completed on Medline and the Embase database, combining different keywords. Original papers published in the English language from 2005 to 2016 with studies involving FDGint in patients affected by NSCLC and treated with radiation therapy or chemo-radiotherapy only were chosen. RESULTS: Twenty-one studies out of 970 in Pubmed and 1256 in Embase were selected, reporting on 627 patients. CONCLUSION: Certainly, the lack of univocal PET parameters was identified as a major drawback, while standardization would be required for best practice. In any case, all these papers denoted FDGint as promising and a challenging examination for early assessment of outcomes during CRT, sustaining its predictivity in lung cancer.

Interim 18F-FDG PET/CT During Chemoradiation Therapy in the Management of Head and Neck Cancer Patients: A Systematic Review.

Positron emission tomography (PET) is an imaging modality widely applied in oncology for tumor staging, volume delineation in radiation therapy planning, and therapy response assessment. F-18 fluorodeoxyglucose (FDG) PET combined with computed tomography plays a significant role in the management of locally advanced head and neck cancer patients in the pretreatment setting to predict outcome and prognosis and after chemoradiation therapy (CRT) to assess tumor response. This review aims to evaluate the use of FDG PET acquired during CRT, ad interim FDG (FDGint), to identify tumor response at an early stage, modify the treatment plan if necessary, or set up alternative strategies to enhance the therapeutic ratio. Most of the studies confirmed the value of FDGint in predicting the response to CRT, whereas a few highlighted the poor predictive value of FDGint compared with FDG acquired 2 to 4 months after the end of CRT, which was well correlated with local and regional control and survival. Such findings deserve to be further analyzed in more homogeneous series with greater patient numbers according to the tumor site and CRT schedules. The best time to assess tumor response during radiation therapy remains a matter of debate, although 2 weeks seems most favorable, still providing the opportunity to adapt the treatment strategy.

Interim 18FDG PET/CT during radiochemotherapy in the management of pelvic malignancies: A systematic review.

18F-fluorodeoxyglucose PET/CT (18F-FDG-PET/CT) is widely applied in oncology for disease staging, assessment of therapy response, relapse diagnosis, follow-up and target volume delineation. In particular, it can detect early response during chemoradiotherapy (interim) because functional modifications usually precede morphological ones. This ability is crucial to the radiation oncologist for the management of patients, to avoid persisting with ineffective therapy - often leading toxicity - and to shift to potentially more effective alternatives. Interim 18F FDG-PET imaging in rectal and cervical cancer, the main malignancies of the pelvic district, has been applied and a broad literature is available, although some results are discordant. This systematic review summarizes the application of 18F FDG-PET/CT during the chemoradiotherapy of locally advanced pelvic malignancies in order to clarify its capability to predict response and prognosis and its potential role to tailor therapy, which seems to be validated in rectal cancer, whilst less conclusive in cervical cancer.

PET/CT with Fluorodeoxyglucose During Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.

OBJECTIVE: The aim of the present study is to evaluate the accuracy of Positron Emission Tomography/Computed Tomography (PET/CT) with Fluorodeoxyglucose ([18F]FDG) to predict treatment response in patients with locally advanced rectal cancer (LARC) during neoadjuvant chemoradiotherapy. PATIENTS AND METHODS: Forty-one LARC patients performed [18F]FDG-PET/CT at baseline (PET0). All patients received continuous capecitabine concomitant to radiotherapy on the pelvis, followed by intermittent capecitabine until two weeks before curative surgery. [18F]FDG-PET/CT was also carried out at 40 Gy-time (PET1) and at the end of neoadjuvant therapy (PET2). PET imaging was analysed semi-quantitatively through the measurement of maximal standardised uptake value (SUVmax) and the tumour volume (TV). Histology was expressed through pTNM and Dworak tumor regression grading. Patients were categorised into responder (downstaging or downsizing) and non-responder (stable or progressive disease by comparison pretreatment parameters with clinical/pathological characteristics posttreatment/after surgery). Logistic regression was used to evaluate SUVmax and TV absolute and percent reduction as predictors of response rate using gender, age, and CEA as covariates. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Survivals were compared by the Log-Rank test. RESULTS: Twenty-three responders (9 ypCR, 14 with downstaged disease) and 18 non-responders showed differences in terms of both early and posttreatment SUVmax percent reduction (median comparison: responder = 63.2%, non-responder = 44.2%, p = 0.04 and responder = 76.9%, non-responder = 61.6%, p = 0.06 respectively). The best predictive cut-offs of treatment response for early and posttreatment SUVmax percent reduction were ≥57% and ≥66% from baseline (p = 0.02 and p = 0.01 respectively). CONCLUSIONS: [18F]FDG-PET/CT is a reliable technique for evaluating therapy response during neoadjuvant treatment in LARC, through a categorical classification of the SUV max reduction during treatment.

Combining standardized uptake value of FDG-PET and apparent diffusion coefficient of DW-MRI improves risk stratification in head and neck squamous cell carcinoma.

OBJECTIVES: To assess the independent prognostic value of standardized uptake value (SUV) and apparent diffusion coefficient (ADC), separately and combined, in order to evaluate if the combination of these two variables allows further prognostic stratification of patients with head and neck squamous cell carcinomas (HNSCC). METHODS: Pretreatment SUV and ADC were calculated in 57 patients with HNSCC. Mean follow-up was 21.3 months. Semiquantitative analysis of primary tumours was performed using SUVmaxT/B, ADCmean, ADCmin and ADCmax. The prognostic value of SUVmaxT/B, ADCmean, ADCmin and ADCmax in predicting disease-free survival (DFS) was evaluated with log-rank test and Cox regression models. RESULTS: Patients with SUVmaxT/B ≥5.75 had an overall worse prognosis (p = 0.003). After adjusting for lymph node status and diameter, SUVmaxT/B and ADCmin were both significant predictors of DFS with hazard ratio (HR) = 10.37 (95 % CI 1.22-87.95) and 3.26 (95 % CI 1.20-8.85) for SUVmaxT/B ≥5.75 and ADCmin ≥0.58 × 10-3 mm2/s, respectively. When the analysis was restricted to subjects with SUVmaxT/B ≥5.75, high ADCmin significantly predicted a worse prognosis, with adjusted HR = 3.11 (95 % CI 1.13-8.55). CONCLUSIONS: The combination of SUVmaxT/B and ADCmin improves the prognostic role of the two separate parameters; patients with high SUVmaxT/B and high ADCmin are associated with a poor prognosis. KEY POINTS: • High SUV maxT/B is a poor prognostic factor in HNSCC • High ADC min is a poor prognostic factor in HNSCC • In patients with high SUV maxT/B , high ADC min identified those with worse prognosis.

Positron emission tomography in the diagnostic work-up of screening-detected lung nodules.

Low-dose computed tomography (CT) screening for lung cancer can reduce lung cancer mortality, but overdiagnosis, false positives and invasive procedures for benign nodules are worrying. We evaluated the utility of positron emission tomography (PET)-CT in characterising indeterminate screening-detected lung nodules. 383 nodules, examined by PET-CT over the first 6 years of the COSMOS (Continuous Observation of Smoking Subjects) study to diagnose primary lung cancer, were reviewed and compared with pathological findings (surgically-treated patients) or follow-up (negative CT for ⩾2 years, considered negative); 196 nodules were malignant. The sensitivity, specificity and accuracy of PET-CT for differentially diagnosing malignant nodules were, respectively, 64%, 89% and 76% overall, and 82%, 92% and 88% for baseline-detected nodules. Performance was lower for nodules found at repeat annual scans, with sensitivity ranging from 22% for nonsolid to 79% for solid nodules (p=0.0001). Sensitivity (87%) and specificity (73%) were high for nodules ⩾15 mm, better (sensitivity 98%) for solid nodules ⩾15 mm. PET-CT was highly sensitive for the differential diagnosis of indeterminate nodules detected at baseline, nodules ⩾15 mm and solid nodules. Sensitivity was low for sub-solid nodules and nodules discovered after baseline for which other methods, e.g. volume doubling time, should be used.

The role of [(18)F]FDG-PET/CT in staging and treatment planning for volumetric modulated Rapidarc radiotherapy in cervical cancer: experience of the European Institute of Oncology, Milan, Italy.

RATIONALE: to evaluate the role of 18F-fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) integrated with computer tomography (CT) scan [(18)F]FDG-PET/CT in the staging and target volume definition in Intensity Modulated RapidarcTM Delivery (RA-IMRT) in cervical cancer. METHODS: From June 2010 to December 2011, 66 patients affected by cervical cancer, candidates for definitive or adjuvant radiochemotherapy, underwent standard staging with CT and magnetic resonance imaging (MRI). All patients underwent [(18)F]FDG-PET/CT in order to exclude distant metastases and to define gross tumor volume (GTV). 40 and 26 patients received exclusive and adjuvant radiotherapy, respectively. RA-IMRT with simultaneous integrated boost (SIB) to the positive disease technique was employed. RESULTS: [(18)F]FDG-PET/CT has changed the stage, and radiotherapy treatment planning was modified in 25% and 7.7 % of patients that received definitive and adjuvant radiotherapy, respectively. Particularly [(18)F]FDG-PET/CT imaging showed metabolically active tumor in lymph nodes area, therefore the stage and the treatment planning changed for these patients. CONCLUSIONS: [(18)F]FDG-PET/CT leads to a better staging and definition of disease and has the potential of showing lymph-node metastasis not only within the pelvis but also in the para-aortic area. In addition, [(18)F]FDG-PET/CT is useful for better definition of the target volume and to produce a 'dose painted' treatment. This might also open the field for escalation dose regimens.

Ipilimumab-induced immunomediated adverse events: possible pitfalls in (18)F-FDG PET/CT interpretation.

A 42-year-old woman underwent resection of a high-risk melanoma of the right thigh. Adjuvant treatment with ipilimumab was then started within a phase III randomised, double-blind clinical trial. F-FDG PET/CT scan showed intense uptake in mediastinal hilar lymph nodes, bilaterally, and in rectus abdominis muscle. Biopsy at the abdominal wall revealed a chronic granulomatous inflammation. After oral steroid treatment, all the areas of abnormal tracer uptake disappeared. Ipilimumab can induce inflammatory immunomediated reactions that should be taken into account to avoid misinterpretation.

Intramedullary spinal cord metastases from breast cancer: detection with (18)F-FDG PET/CT.

A 35-year-old woman, already treated with surgery, chemotherapy, and radiotherapy for a ductal carcinoma of the left breast, underwent an (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) scan for an increase of the serum markers carcinoembryonic antigen (CEA) and cancer antigen 15.3 (CA15.3). The scan showed multiple FDG-avid lesions in the liver and bone. The images also detected two areas of uptake in the dorsal and lumbar spinal cord, which were suspicious for metastases; magnetic resonance imaging (MRI) confirmed these lesions.

Extrapulmonary malignancies detected at lung cancer screening.

PURPOSE: To retrospectively assess the detection rate, histologic characteristics, and clinical stage of screening-detected extrapulmonary malignancies in a population at high risk for lung cancer. MATERIALS AND METHODS: In this institutional review board-approved study, 5201 asymptomatic heavy smokers aged 50 years or older underwent annual low-dose computed tomography (CT) for 5 consecutive years. The 5-year cumulative effective dose was 5 mSv. Subjects with at least one "potentially significant extrapulmonary incidental finding" (PS-IF) were extracted from the study database. An extrapulmonary finding was classified as potentially significant if it required further diagnostic and/or clinical evaluation. In retrospect all clinically relevant information, including findings from diagnostic work-up and final diagnosis of the PS-IF, was collected. On the basis of the information collected, only histologically proved screening-detected extrapulmonary malignancies were eventually included in this study. The percentages of volunteers with extrapulmonary malignancies were calculated, along with 95% confidence intervals (CIs), on the basis of a binomial distribution. RESULTS: After 5 years of CT screening, 27 unsuspected extrapulmonary malignancies were diagnosed, representing 0.5% (27 of 5201 subjects; 95% CI: 0.34%, 0.75%) of volunteers enrolled and 6.2% (27 of 436 findings; 95% CI: 4.12%, 8.88%) of PS-IFs. Eight malignancies were diagnosed at the 1st year of screening, nine at the 2nd year, four at the 3rd year, two at the 4th year, and four at the 5th year. Twelve of the 27 extrapulmonary tumors (44%) were renal carcinomas (n = 7) or lymphomas (n = 5). Twenty-four of the 27 subjects with a malignancy were alive at the most recent follow-up. CONCLUSION: A considerable number of unsuspected extrapulmonary malignancies can be detected in lung cancer screening trials. A careful evaluation of extrapulmonary structures, with particular attention to the kidneys and lymph nodes, is recommended.

A multiple points method for 4D CT image sorting.

PURPOSE: Artifacts affect 4D CT images due to breathing irregularities or incorrect breathing phase identification. The purpose of this study is the reduction of artifacts in sorted 4D CT images. The assumption is that the use of multiple respiratory related signals may reduce uncertainties and increase robustness in breathing phase identification. METHODS: Multiple respiratory related signals were provided by infrared 3D localization of a configuration of markers placed on the thoracoabdominal surface. Multidimensional K-means clustering was used for retrospective 4D CT image sorting, which was based on multiple marker variables, in order to identify clusters representing different breathing phases. The proposed technique was tested on computational simulations, phantom experimental acquisitions, and clinical data coming from two patients. Computational simulations provided a controlled and noise-free condition for testing the clustering technique on regular and irregular breathing signals, including baseline drift, time variant amplitude, time variant frequency, and end-expiration plateau. Specific attention was given to cluster initialization. Phantom experiments involved two moving phantoms fitted with multiple markers. Phantoms underwent 4D CT acquisition while performing controlled rigid motion patterns and featuring end-expiration plateau. Breathing cycle period and plateau duration were controlled by means of weights leaned upon the phantom during repeated 4D CT scans. The implemented sorting technique was applied to clinical 4D CT scans acquired on two patients and results were compared to conventional sorting methods. RESULTS: For computational simulations and phantom studies, the performance of the multidimensional clustering technique was evaluated by measuring the repeatability in identifying the breathing phase among adjacent couch positions and the uniformity in sampling the breathing cycle. When breathing irregularities were present, the clustering technique consistently improved breathing phase identification with respect to conventional sorting methods based on monodimensional signals. In patient studies, a qualitative comparison was performed between corresponding breathing phases of 4D CT images obtained by conventional sorting methods and by the described clustering technique. Artifact reduction was clearly observable on both data set especially in the lower lung region. CONCLUSIONS: The implemented multiple point method demonstrated the ability to reduce artifacts in 4D CT imaging. Further optimization and development are needed to make the most of the availability of multiple respiratory related variables and to extend the method to 4D CT-PET hybrid scan.