[en] To evaluate the feasibility and performance of ultrasound-guided transcutaneous tru-cut biopsy (USGTCB) in selected patients (with stenosis of airways or difficult intubation or contraindication to general anaesthesia) with untreated or previously treated suspicious laryngo-hypopharyngeal masses. Biopsies were performed with a free-hand technique by a single radiologist. Thirty-six USGTCBs were scheduled in 34 patients (24 males, 10 females; age range 47-95 years). Two USGTCBs were not performed, as lesions were not detectable: therefore, 16 USGTCBs were performed for an untreated mass suspicious for malignancy and 18 were performed for a mass suspicious for recurrence after radiotherapy alone, or associated with endoscopic laser surgery or chemotherapy. USGTCB diagnosed 25 squamous cell carcinomas (73.5%) and nine benign lesions (26.5%); no false positives and two false negatives were reported, both in patients previously treated with radiotherapy. The sensitivity, specificity, positive and negative predictive value of the technique was 92.5%, 100%, 100% and 77.7% respectively, with no major complications. Although biopsy under microlaryngoscopy remains the ''gold-standard'' technique, USGTCB is feasible, carries the advantages of avoiding general anaesthesia, is suitable for outpatients and is cost-effective. If applied to selected patients, it could be considered for the histological diagnosis of both primary and recurrent laryngo-hypopharyngeal masses. (orig.)

[en] Dysphagia is one of the most important treatment-related side effects in head and neck cancer (HNC), as it can lead to severe life-threating complications such as aspiration pneumonia and malnutrition. Intensity-modulated radiotherapy (IMRT) could reduce swallowing dysfunction by producing a concave dose distribution and reducing doses to the swallowing-related organs at risk (SWOARs). The aim of this study was to review the current literature in order to compare swallowing outcomes between IMRT and three-dimensional conformal radiotherapy (3DCRT). A search was conducted in the PubMed and Embase databases to identify studies on swallowing outcomes, both clinically and/or instrumentally assessed, after 3DCRT and IMRT. Dysphagia-specific quality of life and objective instrumental data are summarized and discussed. A total of 262 papers were retrieved from the searched databases. An additional 23 papers were retrieved by hand-searching the reference lists. Ultimately, 22 papers were identified which discussed swallowing outcomes after 3DCRT and IMRT for HNC. No outcomes from randomized trials were identified. Despite several methodological limitations, reports from the current literature seem to suggest better swallowing outcomes with IMRT compared to 3DCRT. Further improvements are likely to result from the increased use of IMRT plans optimized for SWOAR sparing. (orig.)

[en] Loco-regionally advanced nasopharyngeal carcinomas can be cured by the combination of chemotherapy and radiotherapy. In Eastern countries, plasma levels of viral Epstein-Barr deoxyribonucleic acid (DNA) are accurate in predicting recurrence, but few data are available in Western populations. The aim of this prospective study was to evaluate the relationship between viral Epstein-Barr DNA copy numbers in plasma and the response rate, progression-free survival and overall survival in a cohort of Western patients with stage IIb-IVb nasopharyngeal cancer. We evaluated plasma samples from 36 consecutive patients treated with induction chemotherapy followed by chemoradiation. EBV copy numbers were determined after DNA extraction using real-time quantitative polymerase chain reaction. Survival curves were estimated using the Kaplan–Meier method. Circulating Epstein-Barr virus DNA levels were measured before treatment, at the end of concomitant chemo- and radiotherapy, and during the follow-up period. Pre-treatment levels significantly correlated with the initial stage and probability of relapse. Their increase was 100% specific and 71.3% sensitive in detecting loco-regional or metastatic recurrence (an overall accuracy of 94.4%). Three-year progression-free and overall survival were respectively 78.2% and 97.1%. The results of this study confirm that patients from a Western country affected by loco-regionally advanced nasopharyngeal carcinoma have high plasma Epstein-Barr virus DNA levels at diagnosis. The monitoring of plasma levels is sensitive and highly specific in detecting disease recurrence and metastases

[en] Multi atlas based segmentation (MABS) uses a database of atlas images, and an atlas selection process is used to choose an atlas subset for registration and voting. In the current state of the art, atlases are chosen according to a similarity criterion between the target subject and each atlas in the database. In this paper, we propose a new concept for atlas selection that relies on selecting the best performing group of atlases rather than the group of highest scoring individual atlases.

Experiments were performed using CT images of 50 patients, with contours of brainstem and parotid glands. The dataset was randomly split into two groups: 20 volumes were used as an atlas database and 30 served as target subjects for testing. Classic oracle selection, where atlases are chosen by the highest dice similarity coefficient (DSC) with the target, was performed. This was compared to oracle group selection, where all the combinations of atlas subgroups were considered and scored by computing DSC with the target subject. Subsequently, convolutional neural networks were designed to predict the best group of atlases. The results were also compared with the selection strategy based on normalized mutual information (NMI).

Oracle group was proven to be significantly better than classic oracle selection (p  <  10⁻⁵). Atlas group selection led to a median  ±  interquartile DSC of 0.740  ±  0.084, 0.718  ±  0.086 and 0.670  ±  0.097 for brainstem and left/right parotid glands respectively, outperforming NMI selection 0.676  ±  0.113, 0.632  ±  0.104 and 0.606  ±  0.118 (p  <  0.001) as well as classic oracle selection.

The implemented methodology is a proof of principle that selecting the atlases by considering the performance of the entire group of atlases instead of each single atlas leads to higher segmentation accuracy, being even better then current oracle strategy. This finding opens a new discussion about the most appropriate atlas selection criterion for MABS. (note)

[en] Purpose: The purpose of this work was to develop and validate an efficient and automatic strategy to generate online virtual computed tomography (CT) scans for adaptive radiation therapy (ART) in head-and-neck (HN) cancer treatment. Method: We retrospectively analyzed 20 patients, treated with intensity modulated radiation therapy (IMRT), for an HN malignancy. Different anatomical structures were considered: mandible, parotid glands, and nodal gross tumor volume (nGTV). We generated 28 virtualCT scans by means of nonrigid registration of simulation computed tomography (CTsim) and cone beam CT images (CBCTs), acquired for patient setup. We validated our approach by considering the real replanning CT (CTrepl) as ground truth. We computed the Dice coefficient (DSC), center of mass (COM) distance, and root mean square error (RMSE) between correspondent points located on the automatically segmented structures on CBCT and virtualCT. Results: Residual deformation between CTrepl and CBCT was below one voxel. Median DSC was around 0.8 for mandible and parotid glands, but only 0.55 for nGTV, because of the fairly homogeneous surrounding soft tissues and of its small volume. Median COM distance and RMSE were comparable with image resolution. No significant correlation between RMSE and initial or final deformation was found. Conclusion: The analysis provides evidence that deformable image registration may contribute significantly in reducing the need of full CT-based replanning in HN radiation therapy by supporting swift and objective decision-making in clinical practice. Further work is needed to strengthen algorithm potential in nGTV localization.

[en] To investigate the correlation between the expression of Epidermal Growth Factor receptor (EGFr) and the reduction of the effective doubling time (T_D) during radiotherapy treatment and also to determine the dose per fraction to be taken into account when the overall treatment time (OTT) is reduced in accelerated radiotherapy of head and neck squamous cell carcinoma (HNSCC). A survey of the published papers comparing 3-years of local regional control rate (LCR) for a total of 2162 patients treated with conventional and accelerated radiotherapy and with a pretreatment assessment of EGFr expression, was made. Different values of T_D were obtained by a model incorporating the overall time corrected biologically effective dose (BED) and a 3-year clinical LCR for high and low EGFr groups of patients (H_E_G_F_r and L_E_G_F_r), respectively. By obtaining the T_D from the above analysis and the sub-sites’ potential doubling time (T_p_o_t) from flow cytometry and immunohistochemical methods, we were able to estimate the average T_D for each sub-site included in the analysis. Moreover, the dose that would be required to offset the modified proliferation occurring in one day (D_p_r_o_l_i_f), was estimated. The averages of T_D were 77 (27-90)_9_5_% days in L_E_G_F_r and 8.8 (7.3-11.0)_9_5_% days in H_E_G_F_r, if an onset of accelerated proliferation T_K at day 21 was assumed. The correspondent H_E_G_F_r sub-sites’ T_D were 5.9 (6.6), 5.9 (6.6), 4.6 (6.1), 14.3 (12.9) days, with respect to literature immunohistochemical (flow cytometry) data of T_p_o_t for Oral-Cavity, Oro-pharynx, Hypo-pharynx, and Larynx respectively. The D_p_r_o_l_i_f for the H_E_G_F_r groups were 0.33 (0.29), 0.33 (0.29), 0.42 (0.31), 0.14 (0.15) Gy/day if α = 0.3 Gy"-"1 and α/β = 10 Gy were assumed. A higher expression of the EGFr leads to enhanced proliferation. This study allowed to quantify the extent of the effect which EGFr expression has in terms of reduced T_D and D_p_r_o_l_i_f for each head and neck sub-site

[en] 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). 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 SUV_m_a_x_T_/_B, ADC_m_e_a_n, ADC_m_i_n and ADC_m_a_x. The prognostic value of SUV_m_a_x_T_/_B, ADC_m_e_a_n, ADC_m_i_n and ADC_m_a_x in predicting disease-free survival (DFS) was evaluated with log-rank test and Cox regression models. Patients with SUV_m_a_x_T_/_B ≥5.75 had an overall worse prognosis (p = 0.003). After adjusting for lymph node status and diameter, SUV_m_a_x_T_/_B and ADC_m_i_n 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 SUV_m_a_x_T_/_B ≥5.75 and ADC_m_i_n ≥0.58 x 10"-"3 mm"2/s, respectively. When the analysis was restricted to subjects with SUV_m_a_x_T_/_B ≥5.75, high ADC_m_i_n significantly predicted a worse prognosis, with adjusted HR = 3.11 (95 % CI 1.13-8.55). The combination of SUV_m_a_x_T_/_B and ADC_m_i_n improves the prognostic role of the two separate parameters; patients with high SUV_m_a_x_T_/_B and high ADC_m_i_n are associated with a poor prognosis. (orig.)

[en] The purpose of this study is to investigate intra-fraction setup variability in hypo-fractionated cranial and body radiotherapy; this is achieved by means of integrated infrared optical localization and stereoscopic kV X-ray imaging. We analyzed data coming from 87 patients treated with hypo-fractionated radiotherapy at cranial and extra-cranial sites. Patient setup was realized through the ExacTrac X-ray 6D system (BrainLAB, Germany), consisting of 2 infrared TV cameras for external fiducial localization and X-ray imaging in double projection for image registration. Before irradiation, patients were pre-aligned relying on optical marker localization. Patient position was refined through the automatic matching of X-ray images to digitally reconstructed radiographs, providing 6 corrective parameters that were automatically applied using a robotic couch. Infrared patient localization and X-ray imaging were performed at the end of treatment, thus providing independent measures of intra-fraction motion. According to optical measurements, the size of intra-fraction motion was (median ± quartile) 0.3 ± 0.3 mm, 0.6 ± 0.6 mm, 0.7 ± 0.6 mm for cranial, abdominal and lung patients, respectively. X-ray image registration estimated larger intra-fraction motion, equal to 0.9 ± 0.8 mm, 1.3 ± 1.2 mm, 1.8 ± 2.2 mm, correspondingly. Optical tracking highlighted negligible intra-fraction motion at both cranial and extra-cranial sites. The larger motion detected by X-ray image registration showed significant inter-patient variability, in contrast to infrared optical tracking measurement. Infrared localization is put forward as the optimal strategy to monitor intra-fraction motion, featuring robustness, flexibility and less invasivity with respect to X-ray based techniques

[en] Purpose: Fatigue is an underevaluated cancer-related and treatment-related symptom. We analyzed fatigue in head and neck cancer patients undergoing radiotherapy (RT). Methods and Materials: A total of 117 patients were enrolled (mean age, 58 years). Radiation therapy (median dose, 66 Gy) was given with either exclusive or postoperative intent in 52 and 65 patients, respectively. Chemotherapy (CT) was added before and/or during RT in 61 patients. The patients completed a 20-item questionnaire (Multidimensional Fatigue Inventory [MFI-20]) before, during (weekly), and after RT. The impact of patient-, tumor-, and treatment-related factors on fatigue was evaluated with unifactorial and multifactorial tests. Results: Fatigue level increased during RT reaching a maximum at Week 6 and then slowly decreased. In multivariate stepwise regression analysis age (inversely related, p < 0.05), psychologic disorders (p < 0.005), and previous head-and-neck surgery (inversely related, p < 0.005) were correlated with higher pre-RT fatigue level. Pre-RT fatigue score (p < 0.0001), induction and/or concomitant CT (p = 0.035), need of cortisone during RT (p = 0.005), and thyroid disorders (p = 0.032) were correlated with higher during-RT fatigue level. Pre-RT fatigue score (p < 0.0001), induction and/or concomitant CT (p < 0.001), and need of cortisone during RT (p < 0.005) were correlated with higher post-RT fatigue level. No impact of gender, performance status, comorbidities other than psychologic and thyroid, tumor stage/site, RT intent, dose, volume, duration, or toxicity was observed. Conclusion: Fatigue affects all patients undergoing RT for head-and-neck cancer, reaches maximum score at the 6th week of RT, and slowly decreases thereafter. Age, thyroid dysfunction, psychologic disorders, pre-RT fatigue score, CT, and cortisone use are correlated with RT-related fatigue levels

[en] Purpose: We performed a phase II study to assess feasibility, pain relief, and toxicity of a tetracaine-based oral gel in the treatment of radiotherapy (RT)-induced mucositis. Methods and Materials: Fifty patients treated with RT for head-and-neck cancer with clinical evidence of acute oral mucositis of grade ≥2 were scheduled to receive the tetracaine gel. A questionnaire evaluating the effect of the gel was given to all subjects. Results: In 38 patients (79.2%), a reduction in oral cavity pain was reported. Thirty-four patients (82.9%) reported no side effect. Seventy-one percent of patients had no difficulties in gel application. Unpleasant taste of the gel and interference with food taste were noticed in 5 (12%) and 16 patients (39%), respectively. Planned RT course was interrupted less frequently in patients who reported benefit from gel application than in patients who did not (p = 0.014). None of the patients who experienced pain relief needed a nasogastric tube, opposite to the patients who did not report any benefit from gel application (p = 0.001). Conclusion: Tetracaine oral gel administration seemed feasible and safe while reducing RT-induced mucositis-related oral pain in a sizeable proportion of treated head-and-neck cancer patients. A trial designed to compare efficacy of this gel vs. standard treatment is warranted