On the cutting edge of intensity modulated radiotherapy and simultaneous integrated boost (IMRT-SIB): The case of a patient with 8 brain metastases.

BACKGROUND: Patients with multiple brain metastases, especially those with more than 3 lesions, usually undergo to palliative whole brain (WB) radiotherapy (RT). METHODS: A breast cancer patient with 8 brain metastases was treated on the brain by a radical RT regimen. Prescription doses were according to the simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) technique with all lesions as well brain irradiated simultaneously in 20 daily fractions. Doses of 40.0 Gy (2.0 Gy/fraction) and 50.0 Gy (2.5 Gy/fraction) were prescribed to the whole brain and to eight individual metastases, respectively. RESULTS: Mean volume of the eight metastases was 8.1 cc (range: 3.8-10.1 cc). For all lesions, the volume receiving 95% of prescribed dose was 100% and dose homogeneity was within 3%. Moreover, maximum doses were less than 105% of prescribed dose, while average mean dose to lesions was 50.6 Gy (range: 49.7-51.5 Gy). Whole brain mean dose was 45.2 Gy. Maximum doses to brainstem and optic chiasma were limited to 44.5 Gy and 42.9 Gy, respectively, while maximum doses to eyes, lens and optic nerves were limited to 9.2 Gy, 4.9 Gy and 41.0 Gy, respectively. From a clinical point of view, subsequent MRI brain controls showed a complete clinical response. Forty months after treatment the patient is disease free and shows no late brain and skin toxicities. CONCLUSION: This case demonstrates the technical feasibility of a SIB-IMRT treatment in patients with more than 3 brain metastases.

Sclerosing adenosis of the breast: report of two cases and review of the literature.

BACKGROUND: Sclerosing adenosis is a benign, usually asymptomatic lobulocentric proliferative process that involves both the epithelial and the mesenchymal component of the breast. It is commonly an incidental finding in perimenopausal women undergoing screening mammography. CASE REPORT: We reported on two patients with sclerosing adenosis assessed with mammography, ultrasound, and contrast-enhanced magnetic resonance imaging. Case 1 was a 21-year-old woman with a palpable lesion in her right breast that was depicted as an irregular mass on contrast-enhanced magnetic resonance imaging. Case 2 was an asymptomatic 42-year-old woman with suspicious ultrasound findings in her left breast; contrast-enhanced magnetic resonance imaging showed regional non-mass-like enhancement associated with increased vascularity. Both patients underwent ultrasound-guided vacuum-assisted biopsy. Sclerosing adenosis does not have distinctive radiological features and can mimic a malignant growth process, thus requiring a diagnostic biopsy. CONCLUSIONS: SA is a common, benign, generally asymptomatic proliferative lesion of the breast. It is associated with a doubling of the risk of developing breast carcinoma, even though its role in carcinogenesis remains to be elucidated. It does not exhibit distinctive MG, US or even MRI features. Since it may mimic a carcinoma it requires further investigation with a diagnostic biopsy.

Imaging of Ganglioneuroma: A Literature Review and a Rare Case of Cystic Presentation in an Adolescent Girl.

Retroperitoneal ganglioneuroma is a rare neuroectodermal tumor with a benign nature. We performed a literature review among 338 studies. We included 9 studies, whose patients underwent CT and/or MRI to characterize a retroperitoneal mass, which was confirmed to be a ganglioneuroma by histologic exam. The most common features of ganglioneuroma are considered to be a solid nature, oval/lobulated shape, and regular margins. The ganglioneuroma shows a progressive late enhancement on CT. On MRI it appears as a hypointense mass in T1W images and with a heterogeneous high-intensity in T2W. The MRI-"whorled sign" is described in the reviewed studies in about 80% of patients. The MRI characterization of a primitive retroperitoneal cystic mass should not exclude a cystic evolution from solid masses, and in the case of paravertebral location, the differential diagnosis algorithm should include the hypothesis of ganglioneuroma. In our case, the MRI features could have oriented towards a neurogenic nature, however, the predominantly cystic-fluid aspect and the considerable longitudinal non-invasive extension between retroperitoneal structures, misled us to a lymphatic malformation. In the literature, it is reported that the cystic presentation can be due to a degeneration of a well-known solid form while maintaining a benign character: the distinguishing malignity character is the revelation of immature cells on histological examination.

Regional and global pancreatic T*2 MRI for iron overload assessment in a large cohort of healthy subjects: normal values and correlation with age and gender.

Multiecho gradient-echo T*2 magnetic resonance imaging is a well-established technique for iron overload assessment but there are few reports concerning the pancreas. The aim of this work was to assess the feasibility and reproducibility of the magnetic resonance imaging for measuring pancreatic regional and global T*2 values, to establish the lower limit of normal in a large cohort of healthy subjects and to correlate the measured values with age and gender. One hundred and twenty healthy subjects (61 males, 51±17 years) underwent magnetic resonance imaging (1.5T) using a multiecho gradient-echo T*2 sequence. T*2 measurements were performed in pancreatic head, body, and tail. The global value was calculated as the mean. Measurement of pancreatic T*2 values was feasible in all subjects. For the T*2 global value the coefficient of variation for intraoperator and interoperator reproducibility were 7.7% and 13%, respectively. The global T*2 values ranged from 24 to 52 ms with the lower limit of normal of 26 ms. There were no significant differences among the regional pancreatic T*2 values. No significant correlation was found between T*2 and patient age or gender. In conclusion, pancreatic T*2 measurements appear to be feasible, reproducible, nontime-consuming and reliable. Gender- and age-related differences concerning pancreatic T*2 were not found.

Concomitant boost radiotherapy and multidrug chemotherapy in the neoadjuvant treatment of locally advanced rectal cancer: results of a phase II study.

BACKGROUND: An intensified multidrug chemotherapy regimen (raltitrexed plus oxaliplatin, Tom-Ox) plus concomitant boost radiotherapy, in the neoadjuvant treatment of locally advanced rectal cancer patients, was shown feasible in our previous study. The aim of this study was to evaluate the efficacy in terms of pathologic complete response to pre-operative therapy. MATERIAL AND METHODS: A Phase II study was designed and clinical stage T3-T4 and/ or N ≥ 1 patients were treated with concomitant boost radiotherapy (55 Gy/5 weeks) plus concurrent chemotherapy (Tom-Ox). The primary endpoint was the assessment of efficacy in terms of clinical and pathologic response to pre-operative therapy. According to the Gehan's design study, 25 patients were enrolled. Toxicity was assessed according to the RTOG-EORTC and CTCAE v.3.0 criteria. RESULTS: Twenty-five consecutive patients were treated. Twenty-two of the 25 (88%) patients had a partial clinical response at the time of pre-operative magnetic resonance imaging (MRI). Only one patient showed progressive systemic disease at pre-surgical revaluation and was subjected only to biopsy to evaluate pathological response. Twenty-four patients (96%) underwent surgery. Overall, pathologic complete response was observed in eight patients (32%; CI 0.95:12-55%) and only microscopic tumor foci (pTmic) in two patients (pT0-mic: 40%; CI 0.95:18-63%). Nineteen patients (76%) showed tumor down-staging. Proctitis and/or diarrhea were the most frequent acute side effects experienced. Eighteen patients had grade 1-2 toxicity (77%); whereas two patients experienced grade 3 toxicity (8%). Two-year Local control and actuarial Disease Free Survival were 100% and 91%, respectively. CONCLUSION. An intensified regimen of concomitant boost radiotherapy plus concurrent raltitrexed and oxaliplatin, can be safely administered in patients with locally advanced rectal cancer. This regimen produces high rates of pathological complete response. Based on available data, this type of treatment could be offered to patients with more advanced tumors (T4 or local recurrence).

Pretreatment MRI Radiomics Based Response Prediction Model in Locally Advanced Cervical Cancer.

The aim of this study was to create a radiomics model for Locally Advanced Cervical Cancer (LACC) patients to predict pathological complete response (pCR) after neoadjuvant chemoradiotherapy (NACRT) analysing T2-weighted 1.5 T magnetic resonance imaging (MRI) acquired before treatment start. Patients with LACC and an International Federation of Gynecology and Obstetrics stage from IB2 to IVA at diagnosis were retrospectively enrolled for this study. All patients underwent NACRT, followed by radical surgery; pCR-assessed on surgical specimen-was defined as absence of any residual tumour. Finally, 1889 features were extracted from MR images; features showing statistical significance in predicting pCR at the univariate analysis were selected following an iterative method, which was ad-hoc developed for this study. Based on this method, 15 different classifiers were trained considering the most significant features selected. Model selection was carried out using the area under the receiver operating characteristic curve (AUC) as target metrics. One hundred eighty-three patients from two institutions were analysed. The model, showing the highest performance with an AUC of 0.80, was the random forest method initialised with default parameters. Radiomics appeared to be a reliable tool in pCR prediction for LACC patients undergoing NACRT, supporting the identification of patient risk groups, which paves treatment pathways tailored according to the predicted outcome.

Preferential patterns of myocardial iron overload by multislice multiecho T*2 CMR in thalassemia major patients.

T*(2) multislice multiecho cardiac MR allows quantification of the segmental distribution of myocardial iron overload. This study aimed to determine if there were preferential patterns of myocardial iron overload in thalassemia major. Five hundred twenty-three thalassemia major patients underwent cardiac MR. Three short-axis views of the left ventricle were acquired and analyzed using a 16-segment standardized model. The T*(2) value on each segment was calculated, as well as the global value. Four main circumferential regions (anterior, septal, inferior, and lateral) were defined. Significant segmental variability was found in the 229 patients with significant myocardial iron overload (global T*(2) <26 ms), subsequently divided into two groups: severe (global T*(2) <10 ms) and mild to moderate (global T*(2) between 10 and 26 ms) myocardial iron overload. A preferential pattern of iron store in anterior and inferior regions was detected in both groups. This pattern was preserved among the slices. The pattern could not be explained by additive susceptibility artifacts, negligible in heavily iron-loaded patients. A significantly higher T*(2) value in the basal slice was found in patients with severe iron overload. In conclusion, a segmental T*(2) cardiac MR approach could identify early iron deposit, useful for tailoring chelation therapy and preventing myocardial dysfunction in the clinical setting.

A systematic review of resectability and survival after concurrent chemoradiation in primarily unresectable pancreatic cancer.

PURPOSE: The objective of this study was to determine the effect on resection rate and survival of neoadjuvant chemoradiotherapy for primarily unresectable locally advanced pancreatic carcinoma. METHODS: A systematic review of recently published literature was performed. Resection rates and survival data were derived from reports published from 2000 onwards. Only recent studies, based on radiotherapy with standard dose and fractionation, have been analyzed. RESULTS: Thirteen studies with a total of 510 patients met selection criteria. A resection rate of 8.3-64.2% was reported (median, 26.5%). Of the operated patients, 57.1-100% (median, 87.5%) had R0 tumor resection. Most papers reported occasional pathological complete responses (CR, 3.0-8.8%). When outcome in all patients was considered, median survival ranged from 9 to 23 (median, 13.3) months, comparing favorably with literature data based on concurrent chemoradiation alone (range, 8.6-13 months). Surprisingly, in patients with unresectable tumor at presentation, median survival after surgery ranged from 16.4 to 32.3 (median, 23.6) months. CONCLUSIONS: The finding of a high proportion of R0 resection among all resections performed confirms the activity of neoadjuvant radiochemotherapy and should not be neglected. Based on these data, patients with unresectable pancreatic cancer without disease progression after chemoradiotherapy should be considered for radical surgery.

Eccrine syringofibroadenoma radiation treatment of an unusual presentation.

Benign skin diseases have seldom been treated with radiotherapy, unless resistant to other treatments. Eccrine syringofibroadenoma (ESFA) is a rare benign eccrine tumor. ESFA very rarely presents bilateral lesions, and seldom a nonsurgical treatment has been proposed. An exceptional case of bilateral ESFA of the foot is presented; radiotherapy was effective in treating both lesions with good cosmetic results.

Extreme complications related to bevacizumab use in the treatment of ovarian cancer: a case series from a III level referral centre and review of the literature.

In patients undergoing debulking surgery for ovarian cancer (OC), bevacizumab-combined chemotherapy has been reported to be associated with an increased incidence of adverse events (AEs). Reports in the literature have noted the overall morbidity of bevacizumab to be between 3.7% and 9%. The aim of this study is to report uncommon and unusual manifestations of morbidity in surgical cases performed at our third level referral centers for gynecologic oncology. Additionally, we review the rare and severe bevacizumab-related complications that have been described in the literature. We defined as "extreme", the particularly rare and/or severe complications up to determining a life-threatening condition or death, which are related to the use of bevacizumab. A case-series of extreme complications registered at our institutions were reported. In addition, a literature search of the PubMed, MEDLINE and EMBASE electronic databases was performed for this review. The studies collected included: 8 randomized controlled trials (RCT) and 5 prospective observational, 1 prospective phase-IV, 10 prospective phase-II, 2 prospective phase-I, and 20 retrospective studies, as well as 9 case reports. Bevacizumab was administered as primary treatment in adjuvant and neo-adjuvant setting in 16 and 5 studies respectively, as treatment for recurrence in 36 trials, and for secondary cytoreductive surgery (SCS) in 3 studies. The overall population administered with bevacizumab numbered 7,096 women. Extreme complications were observed in 591 patients, with a morbidity rate of the 8.3%. Overall, central nervous system (CNS), cardiovascular, gastrointestinal (GI) and primary infectious complications were seen in 22 patients (0.3%), 261 patients (3.7%), 159 patients (2.2%), and 8 patients (0.13%), respectively. Hemorrhagic and wound complications occurred in 18 women (0.25%), and 112 women (1.6%), respectively. Extreme complications related to the use of bevacizumab are rare, and often go unrecognized. The recognition and immediate management of such rare and life-threatening complications in patients treated at third level referral centers could significantly improve patient survival.

Stereobody radiotherapy for nodal recurrences in oligometastatic patients: a pooled analysis from two phase I clinical trials.

Stereotactic body radiotherapy (SBRT) has been shown to achieve high local control rates in limited metastatic burden of disease. Few papers reported on the efficacy of SBRT in nodal oligometastases. The primary aim of the present paper was to analyze the treatment outcome in this setting. Data from DESTROY-1 and SRS-DESTROY-2 phase I clinical trials were reviewed and analyzed. These trials were based on a 5 fractions and a single fraction regimens, respectively. End-points of this analysis were toxicity rates, overall response rate (ORR), and local control (LC). Patients treated between December 2003 and January 2018, with any metastatic site, and primary tumor type and histology were included. One hundred-eighty-one patients (M/F: 93/88; median age: 67, range 37-88) treated with SBRT on 253 nodal lesions were analyzed. Initially, the used technique was 3D-CRT (20.9%), while subsequently treatments were delivered by VMAT (79.1%). The total dose to the PTV ranged between 12 Gy/single fraction to 50 Gy/5 fractions. With a median follow-up of 21 months (2-124), no grade 3 acute or late toxicity was recorded. ORR based on functional imaging was 92.5% with a complete response rate of 76%. Two- and three-year actuarial LC were 81.6% and 76.0%, respectively. Our large pooled analysis confirms the efficacy and safety of SBRT/SRS in patients with nodal metastases and identifies clinical and treatment variables able to predict complete response and local control rate.

Phase I-II studies on accelerated IMRT in breast carcinoma: technical comparison and acute toxicity in 332 patients.

BACKGROUND AND PURPOSE: To evaluate the results in terms of dosimetric parameters and acute toxicity of two clinical studies (MARA-1 and MARA-2) on accelerated IMRT-based postoperative radiotherapy. These results are compared with historical control group (CG) of patients treated with "standard" 3D postoperative radiotherapy. MATERIALS AND METHODS: Prescribed dose to the breast was 50.4Gy in the CG, 40Gy in MARA-1 (low risk of local recurrence), and 50Gy in MARA-2 (medium-high risk of recurrence). The tumor bed total dose was 60.4Gy (sequential 10Gy electron boost), 44Gy (concomitant 4Gy boost), and 60Gy (concomitant 10Gy boost) in CG, MARA-1 and MARA-2 studies, respectively. Overall treatment time was of 32 fractions for CG (6.4weeks); 16 fractions for MARA-1 study (3.2weeks) and 25 fractions for MARA-2 study (5weeks). RESULTS: Three hundred and thirty two patients were included in the analysis. Dosimetric analysis showed D(max) and V(107%) reduction (p<0.001) and D(min) improvement (p<0.001) in the PTV in patients treated with IMRT. Grade 2 acute skin toxicity was 33.6%, 13.1%, and 45.1% in the CG, MARA-1, and MARA-2, respectively (p<0.001), and grade 3 acute skin toxicity was 3.1%, 1.0%, and 2.0%, respectively. Similarly, larger PTV and use of chemotherapy with anthracyclines and taxanes were associated with a greater acute toxicity. With a median follow-up of 31 months, no patients showed local or nodal relapse. CONCLUSIONS: A simplified step and shoot IMRT technique allowed better PTV coverage and reduced overall treatment time (CG, 6.6weeks; MARA-1, 3.2weeks; MARA-2, 5weeks) with acceptable short-term toxicity.

Colitis cystica profunda of the rectum with adenomatous dysplastic features: Radiologic-pathologic correlation.

Colitis cystica profunda is a rare nonneoplastic condition characterized by the presence of mucus-containing cysts in the submucosa of the right colon and rectum. The etiology is unclear, with a few cases reported in the literature. The presenting symptoms and signs may mimic colorectal adenocarcinoma. We report a case of colitis cystica profunda localized in the rectum, investigated by colonoscopy, CT, MRI, and subsequently surgically treated.

Dose escalation in extracranial stereotactic ablative radiotherapy (DESTROY-1): A multiarm Phase I trial.

OBJECTIVE:: A multiarm Phase I clinical trial was performed to define the maximum tolerated dose (MTD) of stereotactic body radiotherapy (SBRT) delivered by non-coplanar conformal beams or volumetric modulated arc therapy technique in seven predefined clinical settings. METHODS:: The (a) and (b) arms investigated primary and metastatic lung cancer differentiated by site of onset, arm (c) included primary or metastatic lesions outside the thorax, the (d) and (e) arms were for in-field reirradiation of recurrence, and finally, the (f) and (g) arms were for boost irradiation to the lesions after an adjuvant RT prescribed dose. A 4 months cut-off after previous irradiation course was fixed to distinguish the boost from the retreatment (<4 vs >4 months, respectively). Patients were prospectively enrolled in study arms according to tumor site, clinical stage and previous treatment. The total dose prescribed to the isocenter, ranged from 20 to 50 Gy according to the protocol design and the doses per fraction ranged from 4 to 10 Gy in 5 days. RESULTS:: A total of 281 patients (M/F: 167/114; median age: 69 years) with 376 lesions underwent SBRT. No acute toxicity was reported in 175 patients (62.3%) while 106 (37.7%) experienced only low-grade (G < 2) acute toxicity. Four patients (all previously irradiated in the same site) showed >Grade 2 toxicity within 6 months from SBRT. With a median follow-up of 19 months, 204 patients (72.6%) did not experience late toxicity, and 77 (27.4%) experienced low grade late toxicity. On per-lesion basis, the 12-and 24 months actuarial local control inside the SBRT field were 84.3 and 73.7 %, respectively. CONCLUSIONS:: SBRT delivered in five consecutive fractions up to the doses evaluated is well tolerated. The MTD was reached in four (a, b, c and f) of the seven study arms. Recruitment for (d), (e) and (g) arms is still ongoing. ADVANCES IN KNOWLEDGE:: In a prospective dose-escalation trial, the MTD of 50 Gy/10 Gy fraction and 35 Gy/7 Gy fraction were defined for primary and metastatic lesions and as boost after prior RT dose ≤50 Gy, respectively.

An atlas for clinical target volume definition, including elective nodal irradiation in definitive radiotherapy of biliary cancer.

Radiotherapy (RT) is a treatment option for advanced biliary tract cancer (BTC), often combined with sequential and/or concurrent chemotherapy. The use of modern RT techniques requires accurate clinical target volume (CTV) definition and delineation. However, guidelines for CTV delineation in BTC are lacking. Therefore, the aim of this study was to propose a computer tomography (CT) atlas for CTV definition of BTC. We previously proposed guidelines to define the nodal CTV (CTV-N) in BTC. In this study, based on a literature analysis, we defined the margins to be added to the gross tumor volume (GTV; subclinical and microscopic disease) to define the primary tumor CTV (CTV-T). An abdominal contrast enhanced planning CT scan was performed on three different patients with unresectable intrahepatic cholangiocarcinoma (CC), extrahepatic CC and gallbladder cancer. The GTV and anatomical reference structures were outlined on CT images. Then, based on our guidelines, the CTV-T and CTV-N were delineated and merged to define the final CTV in the three patients. An atlas, showing the defined CTV, was generated from the reference CT images to illustrate the CTV for intra-hepatic CC, extra-hepatic CC and gallbladder cancer. This atlas can be used as an aid for CTV definition in patients with BTC treated with modern RT techniques.

Spontaneous rectus sheath hematoma: The utility of CT angiography.

We described the utility of computed tomography (CT) angiography in detection of bleeding vessels for a rapid percutaneous arterial embolization of the spontaneous rectus sheath hematoma. A 70-year-old woman comes to our attention with acute abdominal pain and a low hemoglobin level. An unenhanced CT was performed demonstrating a large rectus sheath hematoma. A conservative management was initially established. Despite this therapy, the abdominal pain increased together with a further decrease of hemoglobin values. A CT angiography was then performed, demonstrating an active bleeding within the hematoma and addressing the patient to a rapid percutaneous arterial embolization.

Giant angioleiomyoma of uterus: A case report with focus on CT imaging.

We report a rare case of giant angioleiomyoma located in the uterus and detected in a 37-year-old woman. The uterus is an extremely rare location for angioleiomyoma. The definitive diagnosis is usually obtained only after the histopathologic examination because the imaging criteria are challenging for this disease. We focused our attention on the main computed tomography features able to provide a robust preoperative diagnosis of this rare clinical entity.

Computed tomography angiography of unilateral agenesis of the internal carotid artery: 2 cases report with focus on embryology, collateral pathways, and imaging.

Congenital absence of internal carotid artery (ICA) is a rare anomaly seen in around 0.01% of the population. High incidence of aneurysms is reported in these patients population. Many patients are asymptomatic as the development of a collateral circulation ensures cerebral perfusion. The embryology, the common collateral pathways, and the imaging findings associated with this anomaly are illustrated with 2 new cases. We reported the cases of 2 totally asymptomatic patients at the time of imaging in which ICA agenesis was proved on computed tomography angiography. On imaging, all the most important findings necessary for ICA agenesis diagnosis have been identified and described. Noninvasive imaging techniques are currently the mainstay of ICA agenesis diagnosis.