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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.

OBJECTIVES: : To prospectively compare clinical breast examination, mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (MRI) in a multicenter surveillance of high-risk women. MATERIALS AND METHODS: : We enrolled asymptomatic women aged ≥ 25: BRCA mutation carriers; first-degree relatives of BRCA mutation carriers, and women with strong family history of breast/ovarian cancer, including those with previous personal breast cancer. RESULTS: : A total of 18 centers enrolled 501 women and performed 1592 rounds (3.2 rounds/woman). Forty-nine screen-detected and 3 interval cancers were diagnosed: 44 invasive, 8 ductal carcinoma in situ; only 4 pT2 stage; 32 G3 grade. Of 39 patients explored for nodal status, 28 (72%) were negative. Incidence per year-woman resulted 3.3% overall, 2.1%

Background We describe preoperative computed tomography (CT)guided injection of radiotracer technetium 99m macroaggregates ( 99mTc-MAA) in challenging small lung nodules, intraoperative localization, and resection. Methods Between November 2007 and February 2010, 44 patients with 47 lung nodules which were detected incidentally or at screening and that were 18F-fluorodeoxyglucose positron emission tomography (18F FDG-PET) positive or increasing in size at subsequent CT scans were candidates for surgical biopsy. Inclusion criteria for preoperative percutaneous CT-guided (low-dose technique) 99mTc-MAA localization included having at least one of the following characteristics: nodule size less than 1 cm, subsolid morphology, or distance from the pleura greater than 1 cm. Results Mean nodule size was 11 mm (range, 5 to 24 mm); 24 nodules were nonsolid, 15 nodules were partially solid, and 8 nodules had a solid morphology. Mean distance from the pleura was 11 mm (range, 0 to 35 mm). Localization complications included 13 minor asymptomatic pneumothoraces, 9 parenchymal hemorrhage suffusions, 1 mild allergic reaction to contrast medium, and 2 patients with chest pain after the procedure. Nine patients had mild extravasation of radiotracer into the pleura. In 2 cases, there was an extravasation of a significant quantity of radiotracer into the pleural cavity. Thoracoscopic biopsy was performed in 30 cases, 2 cases were converted to thoracotomy, and 12 patients underwent intentional thoracotomy. Conclusions Asymptomatic subjects with suspicious nodules detected by screening or incidental CT are best candidates due to small lesion size and high percentage of nonsolid morphology, making thoracoscopic biopsy potentially difficult. Radiotracer localization is a safe, versatile, simple technique to help perform diagnosis with a minimally invasive approach in nonpalpable lung lesions. © 2010 The Society of Thoracic Surgeons.

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 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 hierarchical 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.

Purpose The authors assessed the adequacy and sensitivity of CT-guided bone biopsy in 308 procedures performed in 286 cancer patients with suspected bone metastases. Materials and methods An electronic search of our CT-guided bone biopsy database was retrospectively performed to evaluate the adequacy of samples and, in the event of negative samples, whether the patients had radiological progression at the site of biopsy (false negative). Adequacy and false-negative rate were compared with radiological features, biopsy location, specimen length and complications to assess any statistically relevant association with a multivariate logistic regression model. Results A total of 290/308 (94.1 %) samples were adequate. Forty-five patients had normal bone marrow and were followed-up, with evidence of progression at the site of biopsy in 10 cases (false-negative cases); overall sensitivity was 96.7 %. Specimen length was significantly correlated to the probability of an adequate biopsy (p = 0.035) and inversely correlated to the probability to obtain a false-negative result (p = 0.02). We encountered 11/308 (3.5 %) minor complications and no major complications. Conclusion CT-guided biopsy of bone lesions in cancer patients allows for a final diagnosis in 94 % of cases. A specimen longer than 1 cm may lead to a significant result in terms of adequacy and sensitivity. Negative biopsies with positive positron emission tomography or magnetic resonance imaging and specimen shorter than 1 cm should be repeated to avoid a false-negative result. © 2014 Italian Society of Medical Radiology.

http://hdl.handle.net/20.500.11768/96585

Background. In patients with metastatic breast cancer, the evaluation of the biological characteristics of metastatic bone deposits may be a valuable adjunct in clinical practice. We assessed the discordance in expression levels for estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) between primary tumor and bone metastases and its clinical impact on patient management. Material and methods. We retrospectively reviewed 363 CT-guided bone biopsies performed from January 1997 to December 2009. The proportions of ER, PgR and HER2 positive tumors at primary diagnosis and bone metastases, determined by IHC and/or FISH, were compared using McNemar's test. The impact of the biopsy reassessment on treatment choice was evaluated with Fisher's exact test. Results. We selected 109 metastatic breast cancer patients with histologically confirmed bone metastases. Among 107 assessable patients the overall discordance rate was detected in 22 (20.5%) and in 47 (43.9%) patients for ER and PgR, respectively, and in six of 86 assessable patients (6.9%) for HER2 status. The indication to change endocrine therapy occurred in 62% and 30% of patients with ER discordance and ER concordance, respectively (p = 0.01). The indication to change targeted therapy occurred in 67% and 8% of patients with HER2 discordance and HER2 concordance, respectively (p = 0.002). Conclusions. We confirm that biopsy of metastases, including bone metastases, for reassessment of biology should be considered, since it is likely to impact on treatment choice.

http://hdl.handle.net/20.500.11768/96616 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. (C) RSNA, 2011

http://hdl.handle.net/20.500.11768/96538 This study assessed the risk factors for pneumothorax and intrapulmonary haemorrhage after computed tomography (CT)-guided lung biopsies. 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. 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. 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.

Summary Background Indeterminate non-calcified lung nodules are frequent when low-dose spiral computed tomography (LD-CT) is used for lung cancer screening. We assessed the diagnostic utility of a non-invasive work-up protocol for nodules detected at baseline in volunteers enrolled in our single-centre screening trial, and followed for at least 1 year. Methods 5201 high-risk volunteers, recruited over 1 year from October 2004, underwent baseline LD-CT; 4821 (93%) returned for the first repeat LD-CT. Nodules ≤5 mm underwent repeat LD-CT at 1 year; nodules 5.1–8 mm underwent LD-CT 3 months later; lesions >8 mm received combined CT-positron emission tomography (CT-PET). A subset of nodules >8 mm was studied by CT with contrast. Protocol failures were delayed diagnosis with disease progression beyond stage I, and negative surgical biopsy. Results 2754 (53%) volunteers presented one or more non-calcified nodules. Ninety-two lung cancers were diagnosed: 55 at baseline and 37 at annual screening (66% stage I). Among the 37 incident cancers, 17 had a baseline nodule that remained stage I, 7 had a baseline nodule that progressed beyond stage I, and 13 presented a new malignant nodule. Baseline and annual cancers were 79 (1.5%) and 13 (0.2%), respectively. In 15 of 104 (14%) invasive diagnostic procedures, the lesion was benign. Sensitivity, and specificity were 91 and 99.7%, respectively, for the entire protocol; 88 and 93% for CT-PET; and 100 and 59% for CT with contrast. Conclusions The protocol limits invasive diagnostic procedures while few patients have diagnosis delay, supporting the feasibility of lung cancer screening in high-risk subjects by LD-CT. Nevertheless further optimization of the clinical management of screening-detected nodules is necessary.

Objective The main challenge of screening a healthy population with low-dose computed tomography is to balance the excessive use of diagnostic procedures with the risk of delayed cancer detection. We evaluated the pitfalls, difficulties, and sources of mistakes in the management of lung nodules detected in volunteers in the Cosmos single-center screening trial. Methods A total of 5201 asymptomatic high-risk volunteers underwent screening with multidetector low-dose computed tomography. Nodules detected at baseline or new nodules at annual screening received repeat low-dose computed tomography at 1 year if less than 5 mm, repeat low-dose computed tomography 3 to 6 months later if between 5 and 8 mm, and fluorodeoxyglucose positron emission tomography if more than 8 mm. Growing nodules at the annual screening received low-dose computed tomography at 6 months and computed tomography-positron emission tomography or surgical biopsy according to doubling time, type, and size. Results During the first year of screening, 106 patients underwent lung biopsy and 91 lung cancers were identified (70% were stage I). Diagnosis was delayed (false-negative) in 6 patients (stage IIB in 1 patient, stage IIIA in 3 patients, and stage IV in 2 patients), including 2 small cell cancers and 1 central lesion. Surgical biopsy revealed benign disease (false-positives) in 15 cases (14%). Positron emission tomography sensitivity was 88% for prevalent cancers and 70% for cancers diagnosed after first annual screening. No needle biopsy procedures were performed in this cohort of patients. Conclusion Low-dose computed tomography screening is effective for the early detection of lung cancers, but nodule management remains a challenge. Computed tomography-positron emission tomography is useful at baseline, but its sensitivity decreases significantly the subsequent year. Multidisciplinary management and experience are crucial for minimizing misdiagnoses.

Aortopulmonary window coexisting with tetralogy of Fallot (TF) was prospectively diagnosed by two-dimensional (2D) echocardiography and Doppler in an 18-month-old boy; the diagnosis was confirmed by cardiac catheterization and angiocardiography. Surgical correction was performed, but the patient died in the operating room from right ventricular dysfunction. The autopsy showed an adequate surgical repair, but the histologic examination of the lungs demonstrated severe pulmonary vascular disease, which was presumed to be the cause of death.