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Introduction/Background We analyzed early clinical outcomes of carbon ion radiotherapy (CIRT) in the first patients with gynecological malignant mucosal melanoma(g-MMM) treated at CNAO. Methodology Between 2016 and 2018, 9 patients(pts) with g-MMM were treated with CIRT after surgery or in exclusive settings (table 1). They had 7 vaginal(VaM),1 cervical(CM) and 1 vulvar(VuM)MMM. One pt with VaM had been previously irradiated with photons;8 pts are considered inoperable and 1 pt underwent adjuvant CIRT on the small pelvic space after radical surgery without lymphadenectomy. Two pts underwent neoadjuvant and sequential anti-PD-1 immunotherapy. Because of the large volume of macroscopic disease,CM and VuM patients were irradiated with up to a total dose of 28 GyRBE(3 fractions) and 68.8 GyRBE(16 fractions), respectively, to the Clinical Target Volume (CTV) defined as the Gross Tumor Volume (GTV)+uterine cervix and corpus for the CM and GTV+vulva for the VuM. For inoperable VaM, small pelvic space including GTV was irradiated with up to a total dose of 38.7-43 GyRBE followed by a GTV boost of up to a total dose of 68.8 GyRBE in 16 fractions (figure 1). All patients were treated with synchrotron-based scanning carbon ion beams. Early clinical and toxicity profile(according to CTCAE V4.03) were evaluated. Results Treatment was well tolerated and no interruption was needed. For the evaluable pts, toxicity profile was favorable and no G≥2 acute/late toxicities were observed. Overall,for pts with a follow-up≥3 months,median LC ranged from 3 to 13 months( Conclusion Because of the high rate of distant metastasis and unsatisfactory survival benefit, a more conservative treatment approach, instead of extensive surgery, may be warranted. We think that CIRT may serve as a definitive treatment choice for patients with g-MMM. Disclosure Nothing to disclose.

Nowadays, hadrontherapy is increasingly used for the treatment of various tumors, in particular of those resistant to conventional radiotherapy. Proton and carbon ions are characterized by physical and biological features that allow a high radiation dose to tumors, minimizing irradiation to adjacent normal tissues. For this reason, radioresistant tumors and tumors located near highly radiosensitive critical organs, such as skull base tumors, represent the best target for this kind of therapy. However, also hadrontherapy can be associated with radiation adverse effects, generally referred as acute, early-delayed and late-delayed. Among late-delayed effects, the most severe form of injury is radiation necrosis. There are various underlying mechanisms involved in the development of radiation necrosis, as well as different clinical presentations requiring specific treatments. In most cases, radiation necrosis presents as a single focal lesion, but it can be multifocal and involve a single or multiple lobes simulating brain metastasis, or it can also involve both cerebral hemispheres. In every case, radiation necrosis results always related to the extension of radiation delivery field. Multiple MRI techniques, including diffusion, perfusion imaging, and spectroscopy, are important tools for the radiologist to formulate the correct diagnosis. The aim of this paper is to illustrate the possible different radiologic patterns of radiation necrosis that can be observed in different MRI techniques in patients treated with hadrontherapy for tumors involving the skull base. The images of exemplary cases of radiation necrosis are also presented.

To explore the feasibility of 3D printed salivary duct models for the sialendoscopic skills training. Healthy volunteers and patients affected by obstructive salivary gland disorders were submitted to 3 Tesla MR sialography. The MR data underwent an image segmentation process to produce the 3D printed salivary duct prototypes. Sialendoscopies were carried out by three groups of investigators with different levels of endoscopic experience. Realism, usefulness of the training process and potential advantages of the 3D printed models in the preoperative surgical planning were evaluated by means of a specific survey. Four cases were included in our study: one healthy parotid, one submandibular gland, one case of lithiasis and one of stenosis involving the parotid gland. In all cases, the three groups of investigators successfully explored the salivary ducts up to the tertiary branches, detected the cause of obstruction and correctly treated it. Seven untoward events occurred during the operative sialendoscopies. Overall, the questionnaire score was about 79.3%, reflecting a positive impression regarding the models on behalf of all the investigators. 3D printed salivary duct models resulted feasible for the sialendoscopic skills training. The opportunity to reproduce the patient-specific anatomy may add further information useful in the preoperative decision making. These positive results should be verified by further researches and experiences.

Background Pancreatic adenocarcinoma is a high-mortality neoplasm with a documented 5-years-overall survival around 5%. In the last decades, a real breakthrough in the treatment of the disease has not been achieved. Here we propose a prospective, phase II, multicentre, single-arm study aiming to assess the efficacy and the feasibility of a therapeutic protocol combining chemotherapy, carbon ion therapy and surgery for resectable and borderline resectable pancreatic adenocarcinoma. Method The purpose of this trial (PIOPPO Protocol) is to assess the efficacy and the feasibility of 3 cycles of FOLFIRINOX neoadjuvant chemotherapy followed by a short-course of carbon ion radiotherapy (CIRT) for resectable or borderline resectable pancreatic adenocarcinoma patients. Primary outcome of this study is the assessment of local progression free survival (L-PFS). The calculation of sample size is based on the analysis of the primary endpoint “progression free survival” according to Fleming’s Procedure. Discussion Very preliminary results provide initial evidence of the feasibility of the combined chemotherapy and CIRT in the neoadjuvant setting for resectable or borderline resectable pancreatic cancer. Completion of the accrual and long term results are awaited to see if this combination of treatment is advisable and will provide the expected benefits. Trial registration ClinicalTrials.gov Identifier: NCT03822936 registered on January 2019.

Purpose/objective The purpose of this study is to assess the impact of the conversion scheme for relative biological effectiveness (RBE)-weighted dose (DRBE), implemented at our center, on treatment outcomes of adenoid cystic carcinoma (ACC) patients. Material/methods Treatment plans of 78 ACC patients, optimized with the Local Effect Model (LEM), were recalculated with the modified Microdosimetric Kinetic Model (mMKM). DRBE to 95%, 50% and 2% (DV%) of the clinical target volume (CTV), were selected as relevant parameters to compare LEM and mMKM DRBE. The pattern of failure of ACC treatments was analyzed in relation to uncertainties involved in the DRBE translation methodology. Results mMKM recalculations of LEM plans, optimized to a prescription dose of 68.8 Gy(RBE), showed a D50% 8% higher, on average, than the expected value (60.8 Gy(RBE)), closer to the most frequently used mMKM prescription DRBE (64 Gy(RBE)). D95% and D2% deviations, with respect to the optimization goals in the two RBE systems, increased of 0.5% and 14.2%, respectively, due to the steeper mMKM RBE variation along the beam path. Local recurrences were mainly (63%) reported in areas where CTV coverage was not satisfactory in the original LEM plan and the mMKM analysis showed that OARs constraints were too conservative. Conclusion No case of local recurrence could be explained by inadequate mMKM target coverage that was not already present in the LEM plan. New constraints have been defined for optic pathways and brainstem to improve target coverage with no expected increase in tissue complications.

Purpose To derive personalized tumour control probability (TCP) models, using diffusion-weighted (DW-) MRI for defining initial tumour cellular density in skull-base chordoma patients undergoing carbon-ion radiotherapy (CIRT). Materials and methods 67 patients affected by skull-base chordoma were enrolled for a standardized CIRT treatment (70.4 Gy (RBE) prescription dose). Local control information was clinically assessed. For 20 of them, apparent diffusion coefficient (ADC) maps were computed from DW-MRI and then converted into cellular density. Radiosensitivity parameters (α, β) were estimated from the available data through an optimization procedure, taking advantage of a relationship observed between local control and the dose received by at least the 98% of the gross tumour volume. These parameters were fed into two poissonian TCP models, based on the LQ model, being the first (TCPLIT) computed from literature parameters and the second (TCPADC) enriched by a personalized initial cellular density derived from ADC maps. Results The inclusion of the cellular density derived from ADC into TCPADC yielded slightly higher dose values at which TCP = 0.5 (D50 = 38.91 Gy (RBE)) with respect to TCPLIT (D5034.16 Gy (RBE)). This suggested a more conservative approach, even if the prognostic power of TCPADC and TCPLIT, tested with respect to local control, was equivalent in terms of sensitivity (0.867) and specificity (0.600). Conclusions Both TCPADC and TCPLIT exhibited good agreement with a clinically validated information of local control, the former providing more conservative predictions.

This document aims to support the dental professional in choosing the adequate diagnostic technique, minimising the radiation dose in observance of the As Low As Reasonably Achievable (ALARA) principle (7). This principle states that the biological cost can only be justifed when the beneft, that is, the diagnosis, outweighs the risk related to radiation exposure. In this guideline paper, we report recommendations for radiologists, medical physicists, paediatrician, dentists and maxillofacial surgeons, with reference to the specifc felds.

Background The purpose of this study was to identify the factors influencing oncologic outcomes for patients with early-intermediate glottic cancer treated by transoral laser microsurgery (TLM). Methods This was a retrospective mono-institutional study. A total of 590 patients with cTis-cT3 glottic cancer underwent TLM with curative intent. Results TLM alone was performed in 538 patients (91.2%) and TLM followed by adjuvant radiotherapy (RT) was done in 52 (8.8%). Five-year recurrence-free survival (RFS) and 10-year overall survival (OS) were 85.3% and 74.7%, respectively. The larynx-preservation ratio was 95.9%. In particular, from our data, we found that occult metastases were rare (1.2%); preventive tracheotomy was not necessary; the local recurrence rate of Tis was similar to that in the T2 and T3 group; and no major or lethal complications were observed. Conclusion Age (>60 vs ≤60), type of cordectomy (≥IV vs ≤III), status of margins, fixed arytenoid, and pathologic T classification, were the variables associated with RFS, OS, and organ-preservation rate. © 2016 Wiley Periodicals, Head Neck 39: 71–81, 2017

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 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. 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). 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. • 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

Objective To evaluate the diagnostic performance of Ultrasound-guided Transcutaneous Tru-Cut biopsy (USGTCB) of laryngo-hypopharyngeal masses suspicious for malignancy. Furthermore we investigated whether USGTCB is accurate for both untreated masses and suspected recurrences. Materials and methods From August 2004 to July 2014 we prospectively enrolled 66 patients for a total of 68 USGTCBs: 38 USGTCB were performed for a suspicious untreated mass and in 30 for a suspected recurrence. We calculated the sensitivity, specificity, positive predictive value and negative predictive value for all procedures and separately for untreated masses and suspected recurrences. Results USGTCB diagnosed 57 malignancies (51 squamous cell carcinomas, 6 other tumors) and 11 benign lesions. There were no false positives reported, whereas five false negatives were observed: two in patients with an untreated mass, three in patients with a suspected recurrence. Overall, the sensitivity of the technique was 91.9% (95% confidence interval [CI]: 82.2–97.3%); the specificity was 100% (95% CI: 54.1–100%); positive and negative predictive values were 100% (95% CI: 93.7–100%) and 54.5% (95% CI: 23.5–83.1%) respectively, with similar performances in untreated masses and suspected recurrences of SCC. Conclusion USGTCB is an effective procedure for the histological diagnosis of laryngo-hypopharyngeal masses suspicious for malignancy in patients showing contraindications to biopsy via microlaryngoscopy under general, with similar performances for untreated masses and suspected recurrences.

Aim To provide a literature review on risk factors and strategies to prevent acute carotid blowout (CBO) syndrome in patients who underwent reirradiation (reRT) for recurrent head and neck (HN) malignancies. Patients and Methods Inclusion criteria were: 1) CBO following reRT in the HN region, 2) description on patient-, tumor- or treatment-related risk factors, 3) clinical or radiological signs of threatened or impending CBO, and 4) CBO prevention strategies. Results Thirty-five studies were selected for the analysis from five hundred seventy-seven records. Results provided indications on clinical, radiological and dosimetric parameters possibly associated with higher risk of CBO. Endovascular procedures (artery occlusion and stenting) to prevent acute massive hemorrhage in high risk patients were discussed. Conclusion Literature data are still scarce with a low level of evidence. Nevertheless, the present work provides a comprehensive review useful for clinicians as a multidisciplinary pragmatic tool in their clinical practice.

Background: Liposarcomas are the most common soft-tissue sarcomas in adulthood. Orbital and spermatic cord liposarcomas are uncommon and there is no consensus on their management. The treatment of choice is wide excision, which may be destructive and lead to unacceptable morbidity. When surgery is declined by patients and in recurrent disease, management can be challenging. We report two cases of liposarcoma treated with carbon ion radiotherapy at the National Center for Oncological Hadrontherapy (Fondazione CNAO) in Italy. Case Report: A woman with orbital liposarcoma and a man with spermatic cord liposarcoma were referred to our Center and accepted for carbon ion radiotherapy. The treatment was well tolerated and late toxicities were mild. Good local control was achieved in patients. Conclusion: In our experience, carbon ion radiotherapy is an effective and safe option, especially in cases of tumor at high risk for local relapse, in patients with multiple local recurrences, and in patients who refuse destructive surgery.

Purpose The evaluation of the surgical margin in breast conservative surgery is a matter of general interest as such treatments are subject to the critical issue of margin status as positive surgical margins can undermine the effectiveness of the procedure. The relatively unexplored ability of millimeter-wave (mm-wave) spectroscopy to provide insight into the dielectric properties of breast tissues was investigated as a precursor to their possible use in assessment of surgical margins. Methods We assessed the ability of a mm-wave system with a roughly hemispherical sensitive volume of ∼3 mm radius to distinguish malignant breast lesions in prospectively and consecutively collected tumoral and non-tumoral ex-vivo breast tissue samples from 91 patients. We characterized the dielectric properties of 346 sites in these samples, encompassing malignant, fibrocystic disease and normal breast tissues. An expert pathologist subsequently evaluated all measurement sites. Results At multivariate analysis, mm-wave dielectric properties were significantly correlated to histologic diagnosis and fat content. Further, using 5-fold cross-validation in a Bayesian logistic mixed model that considered the patient as a random effect, the mm-wave dielectric properties of neoplastic tissues were significantly different from normal breast tissues, but not from fibrocystic tissue. Conclusion Reliable discrimination of malignant from normal, fat-rich breast tissue to a depth compatible with surgical margin assessment requirements was achieved with mm-wave spectroscopy.

BACKGROUND: Skull-base chordomas are rare and malignant tumors that originate from remnants of the chorda dorsalis (notochord). Adjuvant radiotherapy (RT) is an important predictor of improved progression-free survival and it is recommended after surgery. Exclusive RT represents the treatment of choice for unresectable chordomas. Particle radiotherapy provides dosimetric advantages and higher biological effective dose especially for radioresistant tumors. The aim of the study was to evaluate local control (LC) and toxicity profile of patients (pts) with skull-base chordoma treated with exclusive or adjuvant particle therapy (proton therapy -PT- and carbon ion therapy -CIRT-) MATERIAL AND METHODS: Between September 2011 and December 2017, a total of 134 pts (79 men and 55 women) with a median age of 57 years (range 14–86) with histologically proven skull-base chordoma were treated with particle therapy at National Center of Oncological Hadrontherapy -CNAO. One-hundred and two (76%) pts had previous surgery and complete macroscopic resection was achieved only in 15 pts (20%). Sixty-one pts were treated with PT and 73 with CIRT. The particle choice (proton or carbon ion) was made on personalized basis. Median prescribed total dose was 70,4 Gy RBE (range 35,2-70,4 Gy RBE) in 8–22 fractions (median 16 fractions) of 3-4,4 Gy RBE (median 4,4 Gy RBE) for CIRT, and 74 Gy RBE (range 70–74 Gy RBE) in 27–37 fractions (median 37 fractions) of 2 Gy RBE for PT. Clinical outcome (LC, 3 year local relapse free- LRFS and overall -survival -OS-) and toxicity profile were evaluated. RESULTS: The median follow-up was 32 months (range, 2–64 months). LC was 83%. In pts that underwent complete macroscopic surgery followed by PT, LC was 100%, in pts with uncomplete resection/only biopsy and PT/CIRT, LC was 79%. The 3-year LRFS and OS were 80% and 90% respectively. In field recurrence occurred in 13% (18 pts). In 16 out of 18 cases of recurrences the tumor was in close contiguity to the brainstem. Out of field recurrence was found in 5 pts: 2 cases occurred within surgical way, attributable to surgical seeding, One case of histologically confirmed cervical lymph-node relapse, 2 cases of newly appeared nodules of recurrence. Six pts (4%) developed distant metastasis after a mean interval of 12 months. The toxicity profile was favorable. Only 2 pts developed acute radiation induced high grade toxicity: with oral mucositis (grade 3). High grade (G3-G4) late toxicity occurred in 4% of pts: 1 case of complete visual loss (G4) expected because of optic nerve in field, 1 case of soft tissue necrosis, 2 cases of cranial nerve neuropathy and 2 cases of pituitary dysfunction. CONCLUSION: Particle therapy is the most innovative and conformal RT for treatment of skull base chordomas. It allows to deliver higher (biologically effective) dose levels and to obtain high tumor control rates, minimizing radiation-related side effects.

BACKGROUND: beam radiotherapy (IBRT) is increasingly used for the treatment of head/neck cancers in order to spare radiosensitive structures. The occurrence of brain radiation necrosis (RN) following this modality has been reported in small case series, although its long-term outcome has not been clarified yet. The aim of this study is to define the clinical and radiological course of brain RN after IBRT, with a focus on neuropsychological (NPS) deficits and epilepsy. MATERIAL AND METHODS: Patients were prospectively identified from 07/2014 to 10/2017 during their follow-up at CNAO Foundation. Inclusion criteria were: 1) history of IBRT for a head/neck cancer; 2) age ≥18 years at the time of IBRT; 3) new MRI alterations compatible with brain RN. Enrolled patients underwent multimodal evaluations (including neurological examination, contrast brain MRI, EEG,and NPS testing), at the time of RN detection, after three months and then every six months. RESULTS: A total of 22 patients were identified. All of them had received IBRT for intracranial extraparenchymal tumors. Median age at the time of IBRT was 49 years (range 29–64). IBRT consisted of protons in 9 cases and of carbon ions in 13 cases. Median total dose was 68.8 Gy[RBE] (range 14–76.8). Six patients had been previously irradiated. Median time from the end of IBRT to RN identification was 16 months (range 3–37). In 86% of cases, RN was identified during scheduled MRI scans. RN was located in the temporal lobes in 21 cases (95%). At the time of RN detection, 71% of the patients tested had NPS deficits. Six patients developed seizures (27%). Patients were followed for a median of 23 months (range 4–41). Sixteen patients (73%) needed corticosteroid therapy and 9 (41%) were started on antiepileptic drugs. At last follow-up, 35% of patients still had multidomain NPS deficits. Within the first six months of follow-up, 74% of patients had the appearance of new enhancing lesions o enlargement of previously described lesions on MRI, though in most cases RN was reduced at last radiological follow-up. CONCLUSION: The incidence of RN peaks during the second year after IBRT. Although in most cases RN was identified during scheduled MRI scans, cognitive deficits and symptomatic epilepsy were detected in a large proportion of patients. Long-term outcome is not predictable, as some patients tend to improve over time, while others develop new symptoms. Corticosteroids and antiepileptic drugs are needed in most patients to control symptoms.

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.

Breast cancer is the most common neoplasm in the female population, affecting a woman every eight during her life. The trend of incidence between 2003 and 2017 appears to increase slightly while mortality continues to decrease significantly. Early diagnosis increases the likelihood of having a cure able to overcome the disease, and for this reason mass screening programs are emphasized by all medical institutions. The purpose of screening is early diagnosis in a non-clinical phase. Currently, the reference diagnostic technique in senologic diagnosis is the X-ray mammography, principally for its good resolution. However, the woman exposition to ionizing radiation, as well as the requirement of uncon-fortable breast compression during the test, are pushing the interest toward new imaging techniques. In particular, the attention toward microwave and millimeter waves imaging systems for mass screening is increasing, as this solution could offer several benefits like the non-woman exposition to ionizing radiations. To this aim, a lot of studies have been done around the world, from microwave region to mm-wave frequencies. Starting from 2014, two extensive experimental campaigns have been performed at the European Institute of Oncology in Milan in a wide frequency range up to 50 GHz, involving more than 300 ex-vivo samples derived from around 100 women with ages spanning the range from 14 to 85 years. In this paper, considering the whole database derived from the two experimental campaigns, the correlation between the dielectric properties at 30 GHz of either healthy and tumorous tissues and the patient age, both at sample and women level, is presented. The results show that even at millimetre-wave frequencies a large fraction of the measured healthy samples exhibits dielectric properties compatible with an high adipose content, with a large contrast compared to the most of the tumorous samples, thus confirming the potential use of these frequencies for women older than around 40 years.

Breast cancer places fifth as a cause of death from cancer, especially among women. However, screening techniques have increased the success rate of medical therapies. Based on the well-known limitations of the most commonly used screening methods, microwave imaging has been proposed as an alternative solution. By detecting the dielectric discontinuities in the tissues, microwave imaging systems are able to detect malignant lesions, without exposing the patient to ionizing radiations. With respect to the actual microwave prototypes, the novel system proposed in this paper works at an higher central frequency, i.e. 33.25 GHz, and with a bandwidth of about 13.5 GHz. These two values determine a higher achievable resolution, which would make it possible an early-stage cancer detection. However, at these frequencies the propagation medium is particularly challenging in terms of loss and penetration depth. Consequently, the beam-forming algorithms used to form the image play a crucial role to obtain optimum results even in a lossy medium. In this paper, the feasibility study of a system based on a mm-waves multi-static radar architecture is presented, focusing the attention on the comparison between two different beamforming algorithms.

Breast cancer is one of the leading causes of death among women in the world. In recent years, there has been an increase in the incidence rate, but the rate of death has decreased. This is due to the improvement of diagnostic techniques, which are making possible to have diagnoses ever more precocious. However, all the techniques currently in use show limitations (such as the use of ionizing radiation) and therefore new imaging techniques are being studied. Microwave and millimeter waves imaging systems, based on the different behavior of healthy and tumorous tissues in the interest band, are seen as a viable alternative, so it is crucial to characterize the different human breast tissue up to 50 GHz. In 2014, in collaboration with the European Institute of Oncology in Milan, Italy, and in a project funded by the Italian Association for Cancer Research, a first experimental campaign on ex-vivo samples was conducted. In this paper, the results of a second experimental campaign, conducted in 2016 by the same team, are shown.

Objective The aim of this study is the evaluation of inter-observer variability in the measurement of liver metastases according to RECIST and its influence on response classification. Patients and methods A total of 100 radiologists measured liver target lesions, on pre- and post-chemotherapy CT scans of three patients. Each observer filled out a questionnaire about his personal and work features. The evaluations of a well experienced radiologist, considered as “the gold standard”, were compared to those taken by the observers. The percentage of the observers in agreement with the reviewer, in terms of the response category and in terms of inter-observer variability, was calculated for each patient. Results The percentage of the inter-observer agreement was elevated. Most of the observers in agreement with the reviewer were senior radiologists, while those who disagreed were junior radiologist, but this result did not reach a statistical significance. More than 30% of observers disagreed with the reviewer at least in one of the three cases. Conclusions RECIST measurements are reproducible on a large and heterogeneous population of radiologists. Age and expertise of the radiologist remain the most critical factors: this suggests a revision by well-experienced radiologists in clinical trials.

In an era of personalized treatment, there is a great interest in identifying factors which might predict patient response to radiotherapy (RT). The role of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinoma (HNSCC) remains still controversial. We performed a retrospective analysis on the prognostic value of EGFR in HNSCC patients treated with surgery and postoperative RT through a semiquantitative immunohistochemical analysis of EGFR membrane expression. We retrospectively analyzed 65 HNSCC patients treated in our Institute from 1997 to 2003 who underwent adjuvant RT after surgery. Median follow-up was 43.5 months (range 0.2-173 months). None of these patients were treated with postoperative concomitant chemotherapy. Tumor samples were obtained from surgical specimens. Membrane features (intensity, extension) of EGFR expression were evaluated, and a statistical analysis (univariate and multivariate) was conducted to correlate these parameters with overall survival (OS) and disease-free survival (DFS). Patients with an intense and complete labeling of EGFR presented worse OS and DFS compared with groups obtained by all other possible combination, and the difference was borderline statistically significant (P = 0.08 for OS and P = 0.006 for DFS). Moreover, a stratification of patients was performed considering EGFR expression on the tumor tissue and classifying its distribution as "homogeneous" or "heterogeneous." We found that patients showing an "heterogeneous" EGFR expression distribution had worse OS and DFS compared to the "homogeneous" group of patients. Based on our results, EGFR expression, especially referring to membrane features (semiquantitative analysis), might have a prognostic value for OS and DFS in locally advanced HNSCC treated with surgery and adjuvant RT. Prospective trials could be useful to confirm the prognostic role of EGFR expression and also to assess a predictive role to select that might benefit from more aggressive treatments.

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.

Microwave and mm-wave imaging systems for breast cancer detection are pursued to provide an additional technique with respect to current approaches, mostly based x-rays, ultrasounds, and magnetic resonance. The use of non-ionizing radiation and the relatively low cost are among the most important advantages, but often with resolution or attenuation below expectations for microwave and mm-wave systems, respectively. This paper presents a study based on experimental results, for the first time in the frequency range 0.5–50 GHz, where the potential resolution and propagation losses of breast cancer imaging systems are addressed. In particular, the dielectric properties of the human breast are derived from a systematic clinical campaign involving more than 50 patients, who provided more than 200 ex-vivo tissue samples. As an example, the comparison between a system intended to work at 5 GHz and a system designed at 30 GHz is addressed.

At microwave and mm-wave frequencies, the interactions of the human tissue with electromagnetic fields depend on the dielectric properties of the tissue itself. The knowledge of these properties of healthy and malignant tissues, beyond to be crucial in several biomedical applications, is necessary to fix the safety thresholds in policy-making and the exposure limits for the human body. In particular, breast tissues are of particular interest from the medical and social point of view due to the relatively large diffusion of breast cancer. In literature, experimental data are available up to 20 GHz, and consequently at mm-wave frequencies they are only derived from extrapolations. This paper presents a feasibility study based on the experimental results of a broadband dielectric characterization of breast tissues up to 50 GHz. In particular, two main aspects are addressed. First, the contrast achievable between normal and tumorous tissues, a key parameter for several biomedical applications. Second, the compliance of a mm-wave imaging system for breast cancer detection with the ICNIRP recommendations.

To investigate whether there is an increased signal intensity (SI) of dentate nucleus (DN) and globus pallidus (GP) on unenhanced T1-weighted magnetic resonance imaging (MRI), in patients who had undergone multiple administrations of gadoxetate disodium. We retrospectevely included stage III melanoma patients, who had been previously enrolled in a trial of adjuvant therapy and who had undergone whole-body contrast-enhanced MRIs with gadoxetate disodium every three months for their follow-up. The SI ratios of DN-to-pons and GP-to-thalamus on unenhanced T1-weighted images were calculated. The difference in SI ratios between the first and the last MRI examinations was assessed and a linear mixed model was performed to detect how SI ratios varied with the number of administrations. Eighteen patients were included in our study. The number of gadoxetate disodium administrations ranged from 2 to 18. Paired t-test did not show any significant difference in DN-to-pons (p=0.21) and GP-to-thalamus (p=0.09) SI ratios by the end of the study. DN-to-pons SI ratio and GP-to-thalamus SI ratio did not significantly increase with increasing the number of administrations (p=0.14 and p=0.06, respectively). Multiple administrations of gadoxetate disodium are not associated with increased SI in DN and GP in the brain. • Gadolinium may deposit in the human brain after multiple GBCA administrations. • Gadolinium deposition is associated with increased T1W signal intensity • Increase in signal intensity is most apparent within the DN and GP • Multiple administrations of gadoxetate disodium do not increase T1W signal

We report the case of a man with an advanced nonkeratinizing squamous cell thymic carcinoma harboring c-KIT exon 13 missense mutation K642E. This aberration is rare and has never been described previously in patients with thymic cancers. It has been found in a small number of cases of gastrointestinal stromal tumor and also in several cases of acral and mucosal melanomas. Some of the patients with gastrointestinal stromal tumor or melanoma harboring this rare mutation have had a tumor response when treated with imatinib. In contrast, in our case, the mutation was associated with primary resistance to full doses of imatinib but, at the same time, it was not a cause of resistance to sorafenib.

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.

This review aims to summarize the technique and clinical applications of CT perfusion (CTp) of head and neck cancer. The most common pathologic type (90%) of head and neck cancer is squamous cell carcinoma (HNSCC): its diagnostic workup relies on CT and MRI, as they provide an accurate staging for the disease by determining tumour volume, assessing its extension, and detecting of lymph node metastases. Compared with conventional CT and MRI, CTp allows for obtaining measures of tumour vascular physiology and functional behaviour, and it has been demonstrated to be a feasible and useful tool in predicting local outcomes in patients undergoing radiation therapy and chemotherapy and may help monitor both treatments.

Purpose Apparent diffusion coefficient (ADC) plays a key-role in the context of quantitative diffusion-weighted MRI (DW-MRI) for response assessment in particle-therapy. With this purpose, threshold values defined on ADC could be clinically used to discriminate respondent and not-respondent patients. However, concordant ADC measurements are required for their acceptance as quantitative biomarkers [1] . This study aims at retrospectively investigating the role of ADC maps estimation by comparing different offline strategies with respect to an online map, directly derived from the clinical scanner. Methods DW-MRI at 7 b-values (0, 50, 100, 150, 200, 400, 1000 s/mm2) were acquired during 58 examinations of the brain using a clinical MR scanner (3T). ADC was computed online and offline. For the latter case, DW-MR images at two (ADC_2b: 0–1000 s/mm2; ADC_200b: 200–1000 s/mm2), three (ADC_3b: 50-400–1000 s/mm2) and all (ADC_7b) b-values were used to linearly fit a mono-exponential model exploiting least-square optimization. Voxel-wise absolute differences were computed between any offline and the online ADC for each exam (ΔADC_∗∗b), both on the whole image and on the manually delineated gross tumour volume (GTV). Median values of such differences were then compared using the Friedman test (α = 0.01). Results Evaluating the whole DW-MRI images, ΔADC_2b did not show any statically significant difference with respect to ΔADC_3b, whereas all other pairs did. Focusing on the GTV, differences between any pair were found to be significantly different. The smallest differences were found for ΔADC_7b ( median WHOLE [iqr] = 0.011 [0.009] and median GTV [iqr] = 0.006 [0.001] 10 - 3 mm2/s) and the highest for Δ ADC_200b ( median WHOLE [iqr] = 0.274 [0.034] and median GTV [iqr] = 0.231 [0.034] 10 - 3 mm2/s), whereas Δ ADC_3b and Δ ADC_2b showed intermediate results. Conclusions From this preliminary evaluation, online ADC seems to make use of all available DW images, thus better relating to ADC_7b. Attention must be paid when comparing discriminative threshold values based on online ADC maps and studies aiming at defining the optimal b-values combination for different target tissues should be encouraged.

Head and neck squamous cell carcinoma is the sixth most common cancer diagnosed worldwide and the eighth most common cause of cancer death. Malignant tumors of the oral cavity, oropharynx, and larynx can be treated by surgical resection or radiotheraphy with or without chemotheraphy and have a profound impact on quality of life functions, including swallowing. When surgery is the chosen treatment modality, the patient may experience swallowing impairment in the oral and pharyngeal phases of deglutition. A videofluoroscopic study of swallow enables the morphodynamics of the pharyngeal-esophageal tract to be accurately examined in patients with prior surgery. These features allow an accurate tracking of the various phases of swallowing in real time, identifying the presence of functional disorders and of complications during the short- and long-term postoperative recovery. The role of imaging is fundamental for the therapist to plan rehabilitation. In this paper, the authors aim to describe the videofluoroscopic study of swallow protocol and related swallowing impairment findings in consideration of different types of surgery.

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 (18FDG-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. Copyright © 2012 John Wiley & Sons, Ltd.

This study evaluated intraobserver and interobserver variability in the measurement of apparent diffusion coefficient (ADC) values in breast carcinomas.Twenty-eight patients with solid breast lesions10 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.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%).We found a low intraobserver and interobserver variability in calculating ADC in breast carcinomas, which supports its potential use in routine clinical practice.