Association of quantitative MRI-based radiomic features with prognostic factors and recurrence rate in oropharyngeal squamous cell carcinoma.

Radiomics focuses on extracting a large number of quantitative imaging features and testing both their correlation with clinical characteristics and their prognostic and predictive values. We propose a radiomic approach using magnetic resonance imaging (MRI) to decode the tumor phenotype and local recurrence in oropharyngeal squamous cell carcinoma (OPSCC). The contrast-enhanced T1-weighted sequences from baseline MRI examinations of OPSCC patients treated between 2008 and 2016 were retrospectively selected. Radiomic features were extracted using the IBEX software, and hiegrarchical clustering was applied to reduce features redundancy. The association of each radiomic feature with tumor grading and stage, HPV status, loco-regional recurrence within 2 years, considered as main endpoints, was assessed by univariate analysis and then corrected for multiple testing. Statistical analysis was performed with SAS/STAT® software. Thirty-two eligible cases were identified. For each patient, 1286 radiomic features were extracted, subsequently grouped into 16 clusters. Higher grading (G3 vs. G1/G2) was associated with lower values of GOH/65Percentile and GOH/85Percentile features (p=0.04 and 0.01, respectively). Positive HPV status was associated with higher values of GOH/10Percentile (p=0.03) and lower values of GOH/90Percentile (p=0.03). Loco-regional recurrence within 2 years was associated with higher values of GLCM3/4-7Correlation (p=0.04) and lower values of GLCM3/2-1InformationMeasureCorr1 (p=0.04). Results lost the statistical significance after correction for multiple testing. T stage was significantly correlated with 9 features, 4 of which (GLCM25/180-4InformationMeasureCorr2, Shape/MeanBreadth, GLCM25/90-1InverseDiffMomentNorm, and GLCM3/6-1InformationMeasureCorr1) retained statistical significance after False Discovery Rate correction. MRI-based radiomics is a feasible and promising approach for the prediction of tumor phenotype and local recurrence in OPSCC. Some radiomic features seem to be correlated with tumor characteristics and oncologic outcome however, larger collaborative studies are warranted in order to increase the statistical power and to obtain robust and validated results.

Long-term effects of inhaled budesonide on screening-detected lung nodules.

BACKGROUND: A previously carried out randomized phase IIb, placebo-controlled trial of 1 year of inhaled budesonide, which was nested in a lung cancer screening study, showed that non-solid and partially solid lung nodules detected by low-dose computed tomography (LDCT), and not immediately suspicious for lung cancer, tended to regress. Because some of these nodules may be slow-growing adenocarcinoma precursors, we evaluated long-term outcomes (after stopping the 1-year intervention) by annual LDCT. PATIENTS AND METHODS: We analyzed the evolution of target and non-target trial nodules detected by LDCT in the budesonide and placebo arms up to 5 years after randomization. The numbers and characteristics of lung cancers diagnosed during follow-up were also analyzed. RESULTS: The mean maximum diameter of non-solid nodules reduced significantly (from 5.03 mm at baseline to 2.61 mm after 5 years) in the budesonide arm; there was no significant size change in the placebo arm. The mean diameter of partially solid lesions also decreased significantly, but only by 0.69 mm. The size of solid nodules did not change. Neither the number of new lesions nor the number of lung cancers differed in the two arms. CONCLUSIONS: Inhaled budesonide given for 1 year significantly decreased the size of non-solid nodules detected by screening LDCT after 5 years. This is of potential importance since some of these nodules may progress slowly to adenocarcinoma. However, further studies are required to assess clinical implications. CLINICAL TRIAL NUMBER: NCT01540552.

Computed tomography screening for lung cancer: results of ten years of annual screening and validation of cosmos prediction model.

INTRODUCTION: It is unclear how long low-dose computed tomographic (LDCT) screening should continue in populations at high risk of lung cancer. We assessed outcomes and the predictive ability of the COSMOS prediction model in volunteers screened for 10 years. MATERIALS AND METHODS: Smokers and former smokers (>20 pack-years), >50 years, were enrolled over one year (2000-2001), receiving annual LDCT for 10 years. The frequency of screening-detected lung cancers was compared with COSMOS and Bach risk model estimates. RESULTS: Among 1035 recruited volunteers (71% men, mean age 58 years) compliance was 65% at study end. Seventy-one (6.95%) lung cancers were diagnosed, 12 at baseline. Disease stage was: IA in 48 (66.6%); IB in 6; IIA in 5; IIB in 2; IIIA in 5; IIIB in 1; IV in 5; and limited small cell cancer in 3. Five- and ten-year survival were 64% and 57%, respectively, 84% and 65% for stage I. Ten (12.1%) received surgery for a benign lesion. The number of lung cancers detected during the first two screening rounds was close to that predicted by the COSMOS model, while the Bach model accurately predicted frequency from the third year on. CONCLUSIONS: Neither cancer frequency nor proportion at stage I decreased over 10 years, indicating that screening should not be discontinued. Most cancers were early stage, and overall survival was high. Only a limited number of invasive procedures for benign disease were performed. The Bach model - designed to predict symptomatic cancers - accurately predicted cancer frequency from the third year, suggesting that overdiagnosis is a minor problem in lung cancer screening. The COSMOS model - designed to estimate screening-detected lung cancers - accurately predicted cancer frequency at baseline and second screening round.

Red meat, Mediterranean diet and lung cancer risk among heavy smokers in the COSMOS screening study.

BACKGROUND: To assess whether intake of selected foods and food groups and adherence to a Mediterranean diet are associated with lung cancer risk in heavy smokers. PATIENTS AND METHODS: In the context of a lung cancer screening programme, we invited asymptomatic volunteers, aged 50 years or more, current smokers or recent quitters, who had smoked at least 20 pack-years, to undergo annual low-dose computed tomography. We assessed participants' diet at baseline using a self-administered food frequency questionnaire and calculated their average daily food intake using an ad hoc computer program and determined their alternate Mediterranean diet (aMED) score. We used Cox proportional hazards regression to assess the association between selected food items, beverages and the aMED score and lung cancer risk. RESULTS: During a mean screening period of 5.7 years, 178 of 4336 participants were diagnosed with lung cancer. At multivariable analysis, red meat consumption was associated with an increased risk of lung cancer [hazard ratio (HR) Q4 versus Q1, 1.73; 95% confidence interval (CI) 1.15-2.61; P-value for trend 0.002], while tea consumption (HR for one or more cup/day versus none, 0.56; 95% CI 0.31-0.99; P-value for trend 0.04) and adherence to a Mediterranean diet (HR for aMED ≥ 8 versus ≤ 1, 0.10; 95% CI 0.01-0.77) were significantly associated with reduced lung cancer risk. CONCLUSIONS: Among heavy smokers, high red meat consumption and low adherence to a Mediterranean diet are associated with increased risk of lung cancer.

Roles of computed tomography and [(18)F]fluorodeoxyglucose-positron emission tomography/computed tomography in the characterization of multiple solitary solid lung nodules.

The purpose of this study is to compare the performance of multidetector computed tomography (CT) and positron emission tomography/CT (PET/CT) with [(18)F]fluorodeoxyglucose in the diagnosis of multiple solitary lung nodules in 14 consecutive patients with suspicious lung cancer. CT and PET/CT findings were reviewed by a radiologist and nuclear medicine physician, respectively, blinded to the pathological diagnoses of lung cancer, considering nodule size, shape, and location (CT) and maximum standardized uptake value normalized to body weight (SUVbw max). Nodules were judged malignant or benign. The sensitivity, specificity, and accuracy of the two techniques were compared. CT had a sensitivity, specificity, and accuracy of 93.7, 86.7, and 90.3%, respectively, whereas PET/CT had a sensitivity, specificity, and accuracy of 75, 100, and 87.1%, respectively. Clinical management would have been erroneous in two patients by CT alone and in four patients by PET/CT alone. In one patient, the two techniques misdiagnosed the nodules (2 CT and 1 PET/CT). CT and PET/CT have complimentary roles in characterization of multiple solitary pulmonary nodules. Small nodules are poorly characterized by CT, and small-sized low-SUV malignant nodules are difficult to detect with PET/CT.

A classification of pulmonary nodules by CT scan.

This Image Report aims to briefly describe, giving some imaging examples, the radiological definition of the features of lung nodules as commonly used by radiologists. We hope thus to improve communication and mutual understanding between radiologists and clinicians.

Solitary fibrous tumours: unusual aspects of a rare disease.

BACKGROUND: In literature there are only a few descriptions of the typical presentation of solitary fibrous tumours (SFT) and only a few case reports showing its unusual clinical and radiological features. METHODS: We retrospectively evaluated the computed tomography scans of 36 patients presenting with a histological diagnosis of SFT between 1998 and 2008. RESULTS: We present five cases of SFT with an atypical clinical presentation and radiological features. CONCLUSIONS: SFT can occasionally present with unusual radiological features making a differential diagnosis difficult. Even thought imaging plays a fundamental role in the initial diagnostic approach, final diagnosis in only confirmed by biopsy and histology.

Scale Invariant Feature Transform as feature tracking method in 4D imaging: a feasibility study.

We propose the use of Scale Invariant Feature Transform (SIFT) as a method able to extract stable landmarks from 4D images and to quantify internal motion. We present a preliminary validation of the SIFT method relying on expert user identification of landmarks and then apply it to 4D lung CT and liver MRI data. Results demonstrate SIFT capabilities as an operator-independent feature tracking method.

Assessment of pulmonary fibrosis after radiotherapy (RT) in breast conserving surgery: comparison between conventional external beam RT (EBRT) and intraoperative RT with electrons (ELIOT).

The aim of this study was to assess the frequency and the grade of RT-induced pulmonary fibrosis in patients who underwent EBRT compared to patients who underwent ELIOT. One-hundred-seventy-eight patients enrolled in a prospective randomized phase III trial to compare the efficacy of ELIOT (a single dose of 21 Gy prescribed at the 90% isodose) versus EBRT (50 Gy to the whole breast plus a 10 Gy boost to the tumour bed), underwent a spiral 16-detector row Computed Tomography (CT) examination to assess RT-induced pulmonary fibrosis: 83 patients in the EBRT arm and 95 in the ELIOT arm. All patients (age range 48-75 years) were affected by unicentric infiltrating carcinoma of the breast with diameter < 2.5 cm. This study was approved by our Institutional Ethical Committee and informed consent was obtained from each patient. Two observers, blinded to patient's randomization, independently evaluated each CT examination and assigned a fibrosis score (Grades 0 to 3). Inter-observer agreement for the fibrosis score was evaluated and a consensus between observers was obtained. Differences in fibrosis score between the two arms were evaluated by Chi Square test and Odds Ratio (OR) with 95% Confidence Intervals (CI). Pulmonary fibrosis was diagnosed in 42 patients (23.6%): 38 (90%) were in the EBRT arm and 4 (10%) in the ELIOT arm (p < 0.0001); twenty-six of them were Grade 1 (one ELIOT), fifteen were Grade 2 (three ELIOT) and one was Grade 3. The post-radiotherapy risk in the EBRT arm to develop at least Grade 1 fibrosis was 19 times higher than in the ELIOT one (OR: 19.20; 95%CI: 6.46-57.14) and 6 times higher to develop at least Grade 2 (OR: 5.70; 95%CI: 1.56-20.76). In conclusion, CT detected pulmonary fibrosis in patients treated with ELIOT is significantly less frequent compared to patients treated with EBRT.

Breast MR with special focus on DW-MRI and DCE-MRI.

The use of magnetic resonance imaging (MRI) for the assessment of breast lesions was first described in the 1970s; however, its wide application in clinical routine is relatively recent. The basic principles for diagnosis of a breast lesion rely on the evaluation of signal intensity in T2-weighted sequences, on morphologic assessment and on the evaluation of contrast enhancement behaviour. The quantification of dynamic contrast behaviour by dynamic contrast-enhanced (DCE) MRI and evaluation of the diffusivity of water molecules by means of diffusion-weighted MRI (DW-MRI) have shown promise in the work-up of breast lesions. Therefore, breast MRI has gained a role for all indications that could benefit from its high sensitivity, such as detection of multifocal lesions, detection of contralateral carcinoma and in patients with familial disposition. Breast MRI has been shown to have a role in monitoring of neoadjuvant chemotherapy, for the evaluation of therapeutic results during the course of therapy. Breast MRI can improve the determination of the remaining tumour size at the end of therapy in patients with a minor response. DCE-MRI and DW-MRI have shown potential for improving the early assessment of tumour response to therapy and the assessment of residual tumour after the end of therapy. Breast MRI is important in the postoperative work-up of breast cancers. High sensitivity and specificity have been reported for the diagnosis of recurrence; however, pitfalls such as liponecrosis and changes after radiation therapy have to be carefully considered.

Breast ductal carcinoma and metastatic lymphoma to the contralateral breast in patient with cutaneous non-Hodgkin lymphoma.

Breast lymphoma is a rare condition, both as a primary and a metastatic manifestation. The primary form has an incidence ranging from 0.04% to 0.5% of all breast neoplasms, whereas the metastatic form has an incidence of 0.07%. We hereby report a clinical case of a patient who presented with cutaneous non-Hodgkin lymphoma (NHL) in the left scapulohumeral region treated with surgery followed by radiotherapy (40 Gy total). Three years following radiotherapy, the patient was diagnosed with a left breast infiltrating ductal carcinoma, treated with conservative surgery and adjuvant therapy. The following year, i.e. four years after the initial diagnosis of NHL, two lymphoproliferative relapses occurred: in the left cutaneous scapulohumeral region at the original site of disease, and in the right breast. The aim of this paper is to highlight an uncommon oncologic disorder such as breast lymphoma, highlighting its clinical and radiological manifestations. Some studies reported a possible aetiological role of radiotherapy in the development of breast cancer following treatment of NHL, and in the development of breast cancer following treatment of Hodgkin lymphoma, which could potentially explain our findings.

Diffusion-weighted MR imaging in assessing cervical tumour response to nonsurgical therapy.

PURPOSE: This study was undertaken to assess whether there is a correlation between the response of cervical tumours to nonsurgical therapy (chemo- and/or radiotherapy) and apparent diffusion coefficient (ADC) values. PATIENTS AND METHODS: Seventeen consecutive patients prospectively underwent pelvic magnetic resonance (MR) imaging including diffusion-weighted imaging (DWI) sequences before and after nonsurgical therapy for cervical cancer. A control group of 17 patients without cervical pathology was matched to the study group. Differences in baseline ADC maps between the two groups and within the study group before and after therapy were assessed by nonparametric tests. RESULTS: The diameter and volume of cervical cancers decreased after therapy in 14/17 lesions (responders) and increased in 3/17 lesions (nonresponders). The ADC values of responders increased significantly (p=0.0009). Percent changes in ADC values before and after therapy were higher in responders than nonresponders (p=0.04). There was no significant difference in ADC values between responders and nonresponders at the staging MR examination (p=0.09) and no significant correlation between pretreatment ADC values and percentage of tumour reduction. Tumours with higher percent ADC value increase showed higher tumour reduction volume, but this was not significant (p=0.12). CONCLUSIONS: ADC values of cervical cancer after therapy showed significant differences compared with pretherapy values, particularly for responders.

Should liver metastases of breast cancer be biopsied to improve treatment choice?

BACKGROUND: Currently, the acquisition of tissue from metastatic deposits is not recommended as a routine practice. Our aim was to evaluate the discordance rate of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) receptor status between primary tumor and liver metastases and its potential impact on treatment choice. PATIENTS AND METHODS: We retrospectively analyzed a database including 1250 ultrasound-guided liver biopsies carried out at the European Institute of Oncology from August 1999 to March 2009. ER, PgR, and HER2 status were determined by immunohistochemistry and/or FISH. Differences between proportions were evaluated using Fisher's exact test. RESULTS: We identified 255 consecutive patients with matched primary and liver tissue samples. Changes in ER status were observed in 37 of 255 patients (14.5%). Changes in PgR status were observed in 124 of 255 patients (48.6%). Changes in HER2 status were observed in 24 of 172 assessable patients (13.9%). We observed a discordance in receptor status (ER, PgR, and HER2) between primary tumor and liver metastases, which led to change in therapy for 31 of 255 of patients (12.1%). CONCLUSIONS: Biopsy of metastases for reassessment of biological features should be considered in all patients, when safe and easy to carry out, since it is likely to impact treatment choice.

Risk factors for complications of CT-guided lung biopsies.

PURPOSE: This study assessed the risk factors for pneumothorax and intrapulmonary haemorrhage after computed tomography (CT)-guided lung biopsies. MATERIALS AND METHODS: CT-guided lung biopsies performed between January 2007 and July 2008 were retrospectively evaluated to select the study cohort. Whenever possible, emphysema was quantified by using dedicated software. Features related to the patient, the lesion and the needle and its intrapulmonary path were recorded, along with the pathology findings and operators' experience. The occurrence of pneumothorax and parenchymal haemorrhage was recorded. Univariate and multivariate statistical analyses were performed to assess the association between risk factors and complications. P values <0.05 were considered significant. RESULTS: In 157/222 of the procedures considered, complications were associated with small lesion size and length of the intrapulmonary needle path. Transfissural course and type of needle were associated with pneumothorax using univariate analysis, whereas transfissural course was associated with intrapulmonary haemorrhage using both univariate and multivariate analysis. Emphysema, nodule type, patient position, access site and needle diameter were not significant. Fine-needle aspirates and operator experience were significantly correlated with inadequate biopsy samples. CONCLUSIONS: The size of the lesion and the length of the intrapulmonary trajectory are risk factors for pneumothorax and parenchymal haemorrhage. The transfissural course of the needles is frequently related to pneumothorax and intrapulmonary haemorrhage, and the type of the needle is related to pneumothorax.

Intraobserver and interobserver variability in the calculation of apparent diffusion coefficient (ADC) from diffusion-weighted magnetic resonance imaging (DW-MRI) of breast tumours.

PURPOSE: This study evaluated intraobserver and interobserver variability in the measurement of apparent diffusion coefficient (ADC) values in breast carcinomas. MATERIALS AND METHODS: Twenty-eight patients with solid breast lesions >10 mm underwent conventional contrast-enhanced magnetic resonance imaging (MRI) and diffusion-weighted MRI (DW-MRI). Two observers (expert and trainee) segmented the lesion from the surrounding breast tissue on DW images with high b-value (1,000 s/mm(2)). This analysis was repeated by the expert reader after 6 months. Volumes were analysed to obtain mean, median and standard deviation (SD) of the ADC values. Interobserver and intraobserver variation was analysed using the Bland-Altman graph. RESULTS: All lesions were breast carcinomas, with a mean ADC value of 1.07 × 10(-3) mm(2)/s. The mean of the differences was 0.012 × 10(-3) mm(2)/s, corresponding to an intraobserver variability of 1.1% (limits of agreement: -5%/+8%). The mean interobserver difference was 0.022 × 10(-3) mm(2)/s, corresponding to an interobserver variability of 2% (limits of agreement: -9%/+14%). CONCLUSIONS: We found a low intraobserver and interobserver variability in calculating ADC in breast carcinomas, which supports its potential use in routine clinical practice.

Genomic characterization of asymptomatic CT-detected lung cancers.

Computed tomography (CT) screening of lung cancer allows the detection of early tumors. The objective of our study was to verify whether initial asymptomatic lung cancers, identified by high-resolution low-dose CT (LD-CT) on a high-risk population, show genetic abnormalities that could be indicative of the early events of lung carcinogenesis. We analyzed 78 tumor samples: 21 (pilot population) from heavy smokers with asymptomatic non-screening detected early-stage lung cancers and 57 from 5203 asymptomatic heavy smoker volunteers, who underwent a LD-CT screening study. During surgical resection of the detected tumors, tissue samples were collected and short-term cultures were started for karyotype evaluation. Samples were classified according to the normal (NK) or aneuploid (AK) karyotype. The NK samples were further analyzed by the Affymetrix single-nucleotide polymorphisms (SNPs) technology. Metaphase spreads were obtained in 73.0% of the selected samples: 80.7% showed an AK. A statistically significant correlation was found between presence of vascular invasion and abnormal karyotype. A total of 10 NK samples were suitable for SNPs analysis. Subtle genomic alterations were found in eight tumors, the remaining two showing no evidence to date of chromosomal aberrations anywhere in the genome. Two common regions of amplification were identified at 5p and 8p11. Mutation analysis by direct sequencing was conducted for the K-RAS, TP53 and EGFR genes, confirming data already described for heavy smokers. We show that: (i) the majority of screening-detected tumors are aneuploid; (ii) early-stage tumors tend to harbor a less abnormal karyotype; (iii) whole genome analysis of NK tumors allows for the detection of common regions of copy number variation (such as amplifications at 5p and 8p11), highlighting genes that might be considered candidate markers of early events in lung carcinogenesis.

Non-conventional imaging of lung cancer.

This presentation discusses the optimum magnetic resonance imaging (MRI) sequence for lung cancer assessment in a clinical setting, and the sensitivity and specificity of MRI (alone and in combination with diffusion-weighted imaging (DWI)-MR) compared with those of computed tomography (CT) and fluorodeoxyglucose-positron emission tomography (PET) for lung cancer staging. The role of perfusion studies (by CT or MRI), of DWI-MRI, blood oxygenation level dependent sequences and PET in defining the aggressiveness of lung tumours and in evaluating the response to radiochemotherapy is also discussed.

Perfusion CT in solid body-tumours. Part II: Clinical applications and future development.

Perfusion computed tomography (CTP) has shown great potential in diagnosing tumours and evaluating and predicting treatment response and has been the subject of numerous experimental and clinical studies. Its increasing availability and simplicity allow it to be performed alongside morphological imaging to complete the evaluation of neoplastic lesions. The aim of this paper is to describe our personal experience and review the literature on the applications of CTP in tumours of different body regions, with particular regard to fields of development for new research. Increased clinical application is desirable, especially in relation to a wider use of antiangiogenic drugs. Additional and ideally multicentre studies are necessary to define the role of this technique.

Role of operator experience in ultrasound-guided fine-needle aspiration biopsy of the thyroid.

PURPOSE: Thyroid nodules are commonly encountered in clinical practice, and ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) is the gold standard in diagnosing the pathological nature of undetermined thyroid nodules. The aim of this study was to evaluate whether operator experience influences the diagnostic accuracy of US-guided FNAB. MATERIALS AND METHODS: A total of 700 consecutive US-guided FNAB done by a single radiologist between 2000 and 2007 were retrospectively analysed. The same freehand technique and capillary-action technique with 22- or 25-gauge needles was used for all nodules, All specimens were prepared and fixed without the cytologist on site and were subsequently analysed by two expert cytologists. The procedures were chronologically divided into seven groups and classified as diagnostic or nondiagnostic. RESULTS: The rate of nondiagnostic procedures for each group was 32% in group 1, 13% in group 2, 17% in group 3, 11% in group 4, 10% in group 5, 5% in group 6 and 8% in group 7. No major complications were recorded. CONCLUSIONS: The rate of nondiagnostic US-guided FNAB is heavily dependent on the operator's experience. We estimated that at least 200 procedures need to be performed in order to achieve the levels of diagnostic accuracy reported in the literature. We therefore suggest specific training before operators routinely perform this procedure in clinical practice.

CT perfusion in solid-body tumours. Part I: Technical issues.

Functional imaging is becoming increasingly important in both research and clinical diagnostic radiology. Perfusion computed tomography (CTP) is a readily available and widely used tool that allows an objective measurement of tissue perfusion through the mathematical analysis of data obtained from repeated scans performed after administration of contrast agent. Recently, CTP has been increasingly used in the oncological field, being studied as a potential marker of neoplastic angiogenesis, which is one of the main targets of new tumour therapies. The aim of this paper was to provide the theoretical background and practical guidance for accurately performing CTP and interpreting results of examinations in solid-body tumours. CTP could be a valid tool for functional imaging of tumours if the acquisition technique is robust, if image and data analysis is accurate and if interpretation of results is adequately inserted within a clinical context.