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.

A novel framework for spatial normalization of dose distributions in voxel-based analyses of brain irradiation outcomes.

PURPOSE: To devise a novel Spatial Normalization framework for Voxel-based analysis (VBA) in brain radiotherapy. VBAs rely on accurate spatial normalization of different patients' planning CTs on a common coordinate system (CCS). The cerebral anatomy, well characterized by MRI, shows instead poor contrast in CT, resulting in potential inaccuracies in VBAs based on CT alone. METHODS: We analyzed 50 meningioma patients treated with proton-therapy, undergoing planning CT and T1-weighted (T1w) MRI. The spatial normalization pipeline based on MR and CT images consisted in: intra-patient registration of CT to T1w, inter-patient registration of T1w to MNI space chosen as CCS, doses propagation to MNI. The registration quality was compared with that obtained by Statistical Parametric Mapping software (SPM), used as benchmark. To evaluate the accuracy of dose normalization, the dose organ overlap (DOO) score was computed on gray matter, white matter and cerebrospinal fluid before and after normalization. In addition, the trends in the DOOs distribution were investigated by means of cluster analysis. RESULTS: The registration quality was higher for the proposed method compared to SPM (p < 0.001). The DOO scores showed a significant improvement after normalization (p < 0.001). The cluster analysis highlighted 2 clusters, with one of them including the majority of data and exhibiting acceptable DOOs. CONCLUSIONS: Our study presents a robust tool for spatial normalization, specifically tailored for brain dose VBAs. Furthermore, the cluster analysis provides a formal criterion for patient exclusion in case of non-acceptable normalization results. The implemented framework lays the groundwork for future reliable VBAs in brain irradiation studies.

Synchronous Parotid (Mammary Analog) Secretory Carcinoma and Acinic Cell Carcinoma: Report of a Case.

Mammary analogue secretory carcinoma (MASC) is a recently described low-grade salivary gland malignancy with histologic, immunohistochemical and molecular similarities to secretory carcinoma of the breast, including a specific t(12;15)(p13;q25) resulting in an ETV6-NTRK3 gene fusion. Ultrasound and magnetic resonance imaging frequently document a macrocystic structure. The main differential diagnosis of secretory carcinoma is with low grade acinic cell carcinoma (AciCC). The two can be differentiated with immunohistochemical stains for S100, mammaglobin, carbonic anhydrase VI and DOG-1; the identification of the specific translocation can help to characterize non-typical cases. We report a unique case of synchronous MASC and AciCC presenting in a parotid gland and discuss the implications of the correct identification of the two tumors.

Radiation-induced acute dysphagia : Prospective observational study on 42 head and neck cancer patients.

PURPOSE: Acute toxicity in head and neck (H&N) cancer patients treated with definitive radiotherapy (RT) has a crucial role in compliance to treatments. The aim of this study was to correlate doses to swallowing-associated structures and acute dysphagia. METHODS: We prospectively analyzed 42 H&N cancer patients treated with RT. Dysphagia (grade ≥ 3) and indication for percutaneous endoscopic gastrostomy (PEG) insertion were classified as acute toxicity. Ten swallowing-related structures were considered for the dosimetric analysis. The correlation between clinical information and the dose absorbed by the contoured structures was analyzed. Multivariate logistic regression method using resampling methods (bootstrapping) was applied to select model order and parameters for normal tissue complication probability (NTCP) modelling. RESULTS: A strong multiple correlation between dosimetric parameters was found. A two-variable model was suggested as the optimal order by bootstrap method. The optimal model (Rs = 0.452, p < 0.001) includes V45 of the cervical esophagus (odds ratio [OR] = 1.016) and Dmean of the cricopharyngeal muscle (OR = 1.057). The model area under the curve was 0.82 (95% confidence interval 0.69-0.95). CONCLUSION: Our results suggested that the absorbed dose to the cricopharyngeal muscle and cervical esophagus might play a relevant role in the development of acute RT-related dysphagia.

Feasibility of concurrent chemoradiotherapy with high-dose cisplatin after induction TPF chemotherapy in head and neck cancer: a critical review of the literature and the experience of the European Institute of Oncology.

Many concerns are related to the idea that the acute toxicity of induction chemotherapy (IC) performed with TPF (docetaxel, cisplatin, 5-fluorouracil) could reduce the ability to deliver the subsequent standard concurrent chemoradiotherapy (CRT) in head and neck cancer patients. We performed a critical review of the literature on the toxicity profile of the standard CRT administered after the IC with TPF. A total of 13 papers (including 950 patients) were selected. Results showed that most patients were treated with an adequate radiation total dose although a significant proportion of them (from 15 to 30%) completed the planned treatment with a delay of more than 5 days. A minority of patients were able to be treated with three cycles of concurrent cisplatin, but only few papers reported how many of patients reached the cumulative total dose of almost 200 mg/m2 cisplatin. The rate of deaths due to treatment-related toxicity varied from 0 to 9% (median and mean 2%). Two prospective trials stopped patient enrollment due to acute treatment-related toxicity and because a low number of patients were able to undergo the planned full schedule of cisplatin during the CRT, respectively. Retrospective analysis of 45 patients treated at our institute showed that this schedule was feasible with manageable side effects. In conclusion, the literature data did not provide homogeneous information on the feasibility of the standard CRT after induction TPF. A more uniform data collection of treatment-related toxicity will be helpful in better selecting the patients who might adequately tolerate this multimodality strategy.

High-dose chemotherapy in relapsed or refractory Hodgkin lymphoma patients: a reappraisal of prognostic factors.

High-dose chemotherapy (HDCT) has a consolidated role in the treatment of patients with refractory or relapsed Hodgkin lymphoma (HL). We report clinical results of 97 HL patients who underwent HDCT for refractory (62 patients) or relapsed (35 patients) diseases in Istituto Europeo di Oncologia, from 1995 to 2009. Treatment included high-dose carmustine, etoposide, cytarabine and melphalan in 84 patients and high-dose idarubicin and melphalan in 13 patients with subsequent peripheral hemopoietic stem cells transplant. Outcomes were evaluated in terms of progression-free survival (PFS) and overall survival (OS). In order to identify prognostic factors for outcome, a multivariate analysis for age, sex, disease status (refractory/relapsed), disease stage, B symptoms, presence of extranodal involvement, bulky disease, elevated lactate dehydrogenase, number of previous chemotherapy lines, remission status before transplant, 18F-fluoro-deoxy-d-glucose positron emission tomography ((18) FDG-PET) status before and after transplant was done. A clinical response was achieved in 91% of patients, with complete remissions in 76/97 patients. With a median follow-up of 45 months (range 1-164 months), 5-year PFS and OS were 64% and 71%, respectively. Remission status after induction therapy, 18F-fluoro-deoxy-d-glucose positron emission tomography status before and after transplant were the most important prognostic factors for PFS and OS in univariate or multivariate analyses. HDCT is able to induce a high remission rate and a prolonged PFS in more than 50% of the patients with refractory and relapsed HL.

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.

Identical Mutation in SH3BP2 Gene Causes Clinical Phenotypes with Different Severity in Mother and Daughter - Case Report.

Cherubism is a particular form of fibrous dysplasia of the jaws. Familial occurrence was reported in most cases. The condition is a rare hereditary disorder with autosomal dominant inheritance, with complete penetrance in males and incomplete penetrance in females and variable expressivity. It is known to be caused by mutations in the gene encoding SH3-domain binding protein 2, SH3BP2 gene. Major diagnostic criteria are cherubic facial appearance, painless hard enlargement of the jaws, and frequently associated dental abnormalities. The aim of the study was to analyze clinical and genetic features of cherubism in a family with 3 daughters in which the youngest one was affected. Clinical and radiographic examinations, hematological and biochemical evaluations and biopsy were performed. Molecular genetic analysis consisted of PCR amplification and direct sequencing of selected exons of the SH3BP2 gene. Cherubism was suspected based on clinical and radiographic examinations of the 9-year-old daughter. She presented asymmetrical enlargement of the mandible, speech and swallowing problems and dental abnormalities on the lower jaw. There was no history of similar clinical findings in any of the daughters or the parents of the affected girl. Abnormal results were obtained by genetic analysis. A c.1244G>A mutation was identified in exon 9 of the SH3BP2 gene in the asymptomatic mother and her affected daughter. The identified mutation in the SH3BP2 gene is probably disease-causing. The asymptomatic mother transmitted the gene mutation to her affected daughter. Our results confirm the reduced penetrance and variable expression of the gene mutation.

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.

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.

CT perfusion in oncology: how to do it.

Robust technique and accurate data analysis are required for reliable computed tomography perfusion (CTp) imaging. Multislice CT is required for high temporal resolution scanning; 16-slice (or 64-slice) scanners are preferred for adequate volume coverage. After tumour localization, the volume of CTp imaging has to be positioned to include the maximum visible area of the tumour and an adequate arterial vessel. Dynamic scans at high temporal resolution (at least 1-s gantry rotation time) are performed to visualize the first pass of contrast agent within the tumour; repeated scans with low temporal resolution can be planned for late enhancement assessment. A short bolus of conventional iodinated contrast agent, preferably with high iodine concentration, is power injected at a high flow rate (>4 ml/s) in the antecubital vein. The breath-hold technique is required for CTp imaging of the chest and upper abdomen to avoid respiratory motion; free breathing is adequate for CTp imaging of the head, neck and pelvis. Using dedicated software, a region of interest (ROI) has to be placed in an adequate artery (as arterial input) to obtain density-time curves; according to different kinetic models, colour maps of different CTp parameters are generated and generally overlaid on CT images. Additional ROIs can be positioned in the tumour, and in all other parts of the CTp volume, to obtain the values of the CTp parameters within the ROI.

Laser surgery of early glottic cancer in elderly.

Aim of this retrospective study is to evaluate the impact of transoral laser surgery of early glottic cancer in elderly patients in terms of feasibility, disease-free survival, overall survival and organ preservation, in a single Institute (European Institute of Oncology). A total of 122 patients (male/female ratio 113/9), over 70s with untreated early stage glottic cancer, were consecutively evaluated and treated at the European Institute of Oncology from 2000 to 2008. None had contraindications to general anaesthesia and all patients signed informed consent to this surgical treatment. The severity of pre-operative comorbidities and the intra-operative risk were evaluated according to the American Society of Anaesthesiologists Grading classification. All patients underwent laser cordectomies according to the European Laryngological Society classification. Histopathological examination demonstrated no evidence of tumour (pT0) in 19 patients (calculated only in patients with a previous vocal cord biopsy positive for squamous cell carcinoma), pTis in 18, pT1a in 53, pT1b in 16, pT2 in 14 and pT3 in 2, respectively. A 10-year overall survival, a tumour specific survival and a laryngeal tumour-specific survival were, respectively, 64.9%, 84.8% and 94.3%. In conclusion, transoral laser surgery is feasible in elderly patients with early stage glottic cancer, providing good results in terms of disease-free survival, organ preservation and quality of life. Our group of elderly patients had no intra-operative or post-surgical complications and resumed normal activities the day after discharge from hospital. Considering these factors, we can assess, that transoral laser surgery, therefore, represents a modern treatment that should be offered as an alternative to conventional radiotherapy in elderly patients with early glottic cancer referred to medical centres with expertise for this surgical procedure.

Intensified ChlVPP/ABVVP chemotherapy regimen and pegfilgrastim support in advanced Hodgkin lymphoma.

We present feasibility, toxicity and efficacy results of an intensified six-cycle ChlVPP/ABVVP regimen in advanced Hodgkin lymphoma (HL). From February 2004 to August 2007, 82 consecutive eligible patients were enrolled. According to the Hasenclever index, 64 patients (78%) were considered at low risk, 15 (18%) at intermediate and 3 (4%) at high risk. The most relevant toxicity was haematological: grade 3-4 neutropenia occurred in 32% of patients, grade 3-4 anaemia in 26% of patients. Severe infections and febrile neutropenia were observed in 8% of patients. With a median follow-up of 35 months (range 12-55), the three-year freedom from treatment failure (FFTF) and overall survival (OS) were 75% (95% CI 65%-86%) and 94% (95% CI 87%-99%), respectively. The intensified ChlVPP/ABVVP regimen in advanced HL is effective, does not seem to differ from standard regimens in terms of FFTF and OS and showed a favourable toxicity profile.

Long-term outcomes of a pilot CT screening for lung cancer.

BACKGROUND: Low-dose computed tomography (CT) screening can detect early stage lung cancer in high-risk populations. However, no data on repeated annual screening over more than 5 years are available, and the impact of screening on lung cancer mortality is controversial. METHODS: We analysed outcomes in high-risk asymptomatic volunteers (smokers and former smokers, >50 years) enrolled in a pilot study over 1 year from June 2000, who received annual low-dose CT for 7 years. Cumulative lung cancer incidence and survival were represented by Kaplan-Meier curves. Standardized incidence and mortality ratios were used to estimate risks relative to the general Italian and US population. RESULTS: Compliance was 86% at the end of the seventh year in 1035 recruited volunteers (71% men, mean age 58 years). Lung cancer was diagnosed in 54 (5.3%); radical surgery was possible in 48/54 (87%); 39/54 (72%) had stage I disease. Five-year survival was 63% overall, 89% for stage I cases. During 6308 person-years of observation, 47 participants had died versus 75 expected in the Italian general population standardised for age and sex. Fourteen lung cancer deaths were registered versus 27 expected in a standardised US smoker population. CONCLUSIONS: Seventy percent of screening-diagnosed patients had stage I disease, and the survival of screen-detected cancer patients was high. Lung cancer mortality was favourable compared to age- and sex-matched population of US smokers, suggesting that mortality can be lowered by screening, although larger trials with longer follow-up are necessary to confirm these findings.

Magnetic resonance imaging of primary breast lymphoma.

PURPOSE: Primary lymphomas of the breast (PBNHL) are uncommon. Magnetic resonance imaging (MRI) features of these malignancies can be relevant in establishing the extent of disease and planning the appropriate therapeutic strategy, usually represented by chemo- and radiotherapy, rather than surgery. The purpose of this study was to assess MRI features of PBNHL. MATERIALS AND METHODS: MRI examinations performed on seven patients with known PBNHL were retrospectively evaluated. Lesions were analysed for both morphology and kinetics and classified according to the Breast Imaging Reporting and Data System (BI-RADS) categories. RESULTS: The mean MRI maximum diameter was 44 mm (range 12-69). Six lesions showed a mass-like enhancement; one lesion showed a non-mass-like enhancement. For mass-like lesions, kinetic curve assessment of initial rise showed slow enhancement in one lesion, rapid enhancement in four lesions and medium enhancement in one lesion. Assessment of delayed enhancement showed plateau in five lesions and washout in one lesion. MRI BI-RADS categories were distributed as follows: one BI-RADS II, one BI-RADS III, three BI-RADS IV and two BI-RADS V. CONCLUSIONS: MRI features of primary breast lymphomas in this study cohort suggest that the occurrence of a PBNHL should be considered in the presence of large enhancing lesions of the breast, especially if associated with skin thickening. MRI may also have an important role in the assessment of response to therapy and diagnosis of recurrence.

Intra- and interobserver agreement and impact of arterial input selection in perfusion CT measurements performed in squamous cell carcinoma of the upper aerodigestive tract.

BACKGROUND AND PURPOSE: CT Perfusion (CTP) has shown potential for assessing head and neck tumors. Our purposes were to assess the inter- and intraobserver agreement of CTP measurements and to investigate whether the selection of arterial input, ipsilateral versus contralateral to the tumor or left-versus-right external carotid artery (ECA), may affect CTP measurements in patients with squamous cell carcinoma (SCCA) of the upper aerodigestive tract. MATERIALS AND METHODS: Twenty-six patients with SCCA were enrolled in this prospective study and underwent CTP. Data were analyzed by 2 expert readers and by an inexperienced reader for interobserver agreement and by the 2 expert readers for intraobserver agreement assessment, by using the ECA ipsilateral to tumor site as arterial input. All 3 readers repeated their analysis by using the ECA contralateral to tumor site as arterial input. Inter- and intraobserver agreement was assessed by using the Bland-Altman approach; CTP measurements by using ipsilateral-versus-contralateral or left-versus-right ECA were compared by using the Wilcoxon signed rank test. RESULTS: The geometric mean of the ratios (95% limits of agreement) for inter- and intraobserver agreement ranged from 0.96 (0.75-1.23) to 1.00 (0.92-1.10) for blood flow (BF), from 0.88 (0.63-1.21) to 1.00 (0.88-1.14) for blood volume (BV), from 0.96 (0.64-1.44) to 0.98 (0.76-1.27) for mean transit time (MTT), and from 0.85 (0.41-1.76) to 1.14 (0.70-1.86) for permeability surface area product (PS). Significantly higher tumor PS and MTT for 2 readers and lower tumor BF for 1 of 3 readers were observed when the arterial input was placed in the left ECA. CONCLUSIONS: BF, BV, and MTT demonstrated higher inter- and intraobserver agreement than PS. The selection of arterial input, right-versus-left ECA, may determine changes in CTP measurements in patients with SCCA of the upper aerodigestive tract.

Bisphosphonates and jaw osteonecrosis in patients with advanced breast cancer.

BACKGROUND: In recent years, several cases of mandibular necrosis associated with long-term use of bisphosphonates have been reported. The estimated incidence varies from 1% to 4.6%. PATIENTS AND METHODS: We conducted an observational study with the aim of determining the incidence of jaw osteonecrosis in advanced breast cancer patients with bone metastases under bisphosphonate treatment and to identify subjects at higher risk of developing this complication evaluating preclinical signs. We considered two groups of patients. All the patients complaining of odontostomatological symptoms underwent maxillary CT scan and maxillo-surgeon clinical examination. Asymptomatic patients were asked to perform a standard orthopantomography (OPT). RESULTS: From February 2005 to October 2005, we observed five patients with jaw bone necrosis (6%). Diagnosis was radiological and clinical. In two patients a confirmatory biopsy was performed. In the same time interval, OPTs were collected from 76 asymptomatic patients. Three OPTs revealed radiological features of suspicious mandibular necrosis. Maxillary CT scan confirmed the presence of an osteolityc area with signs of periosteal reaction. All the three patients were referred to maxillo-surgeon and two out of three patients underwent mandibular biopsy, but histopathological results were not conclusive. CONCLUSIONS: In our experience, the incidence of jaw bone necrosis in breast cancer patients seems to be higher than in other reports (6%). Radiological features of suspicious jaw necrosis were observed in three asymptomatic patients. We do not know how these findings should be considered. Anyway, standard OPT is a simple procedure, and may allow identification of periodontal conditions that in some way can predispose to the development of this uncommon event.