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1.  Accuracy of 18F-flurodeoxyglucose-positron emission tomography/computed tomography in the staging of newly diagnosed nasopharyngeal carcinoma: a systematic review and meta-analysis 
Radiology and Oncology  2014;48(4):331-338.
Background
The specific role of 18F-flurodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in staging of nasopharyngeal carcinoma (NPC) remains to be validated. A systematic review and meta-analysis were performed to assess the accuracy of staging FDG-PET/CT for newly diagnosed NPC.
Methods
We searched various biomedical databases and conference proceedings for relevant studies. We determined the pooled sensitivities and specificities, diagnostic odds ratios (DOR) and constructed summary receiver operating characteristic (SROC) curves using the hierarchical regression model.
Results
15 relevant studies including 851 patients were identified. Five addressed primary tumor (T), nine addressed regional lymph nodes (N) and seven addressed distant metastasis (M). The combined sensitivity estimate for FDG-PET/CT in T classification was 0.77 (95% confidence interval [CI] 0.59–0.95). For N classification, combined sensitivity was 0.84 (95% CI 0.76–0.91), specificity was 0.90 (95% CI 0.83–0.97), DOR was 82.4 (23.2–292.6) and Q*-index was 0.90. For M classification, the combined sensitivity estimate was 0.87 (95% CI 0.74–1.00), specificity was 0.98 (95% CI 0.96–1.00), DOR was 120.9 (43.0–340.0) and Q*-index was 0.89.
Conclusion
FDG-PET/CT showed good accuracy in N and M but not T classification for newly diagnosed NPC. FDG-PET/CT, together with Magnetic resonance imaging (MRI) of the nasopharynx, should be part of the routine staging investigations.
doi:10.2478/raon-2014-0011
PMCID: PMC4230552  PMID: 25435845
nasopharyngeal carcinoma; PET/CT; staging; accuracy; meta-analysis
2.  Searching for primaries in patients with neuroendocrine tumors (NET) of unknown primary and clinically suspected NET: Evaluation of Ga-68 DOTATOC PET/CT and In-111 DTPA octreotide SPECT/CT 
Radiology and Oncology  2014;48(4):339-347.
Background
To evaluate the clinical efficacy of In-111 DTPA octreotide SPECT/CT and Ga-68 DOTATOC PET/CT for detection of primary tumors in patients with either neuroendocrine tumor of unknown primary (NETUP) or clinically suspected primary NET (SNET).
Patients and methods.
A total of 123 patients were included from 2006 to 2009, 52 received Ga-68 DOTATOC PET/CT (NETUP, 33; SNET, 19) and 71 underwent In-111 DTPA octreotide SPECT/CT (50; 21). The standard of reference included histopathology or clinical verification based on follow-up examinations.
Results
In the NETUP group Ga-68 DOTATOC detected primaries in 15 patients (45.5%) and In-111 DTPA octreotide in 4 patients (8%) (p < 0.001); in the SNET group, only 2 primaries could be detected, all by Ga-68 DOTATOC. In patients with NETUP, primary tumors could be found significantly more often than in patients with SNET (p = 0.01). Out of these 21 patients 14 patients were operated.
Conclusion
Ga-68 DOTATOC PET/CT is preferable to In-111 DTPA octreotide SPECT/CT when searching for primary NETs in patients with NETUP but should be used with caution in patients with SNET.
doi:10.2478/raon-2014-0018
PMCID: PMC4230553  PMID: 25435846
NET; CUP; Ga-68 DOTATOC PET/CT; In-111 DTPA octreotide SPECT; clinically suspected NET
3.  The role of elastosonography, gray-scale and colour flow Doppler sonography in prediction of malignancy in thyroid nodules 
Radiology and Oncology  2014;48(4):348-353.
Background
Ultrasound is as a noninvasive method commonly used in the work-up of thyroid nodules. This study aimed to evaluate the usefulness of sonographic and elastosonographic parameters in the discrimination of malignancy.
Patients and methods.
150 thyroid nodules were evaluated by gray-scale, Doppler and elastosonography. The cytological analysis revealed that 141 nodules were benign and 9 were malignant.
Results
Orientation of the nodule was the only sonographic parameter associated with malignancy (p = 0.003). In the strain ratio analysis the best cut-off point was 1.935 to discriminate malignancy (p = 0.000), with 100% sensitivity, 76% specificity, 100% negative predictive value, 78.5% positive predictive value and 78% accuracy rate. There was a statistically significant correlation between the elasticity score and malignancy (p = 0.001). Most of the benign nodules had score 2 and 3, none of them displayed score 5. On the other hand, none of the malignant nodules had score 1 and 2, most of them displaying score 5.
Conclusions
A change in the diagnostic algorithm of the thyroid nodules should be considered integrating the elastosonographic analysis.
doi:10.2478/raon-2014-0007
PMCID: PMC4230554  PMID: 25435847
ultrasound; Doppler; elastosonography; thyroid, malignancy
4.  Differential S-phase progression after irradiation of p53 functional versus non-functional tumour cells 
Radiology and Oncology  2014;48(4):354-360.
Background
Many pathways seem to be involved in the regulation of the intra-S-phase checkpoint after exposure to ionizing radiation, but the role of p53 has proven to be rather elusive. Here we have a closer look at the progression of irradiated cells through S-phase in dependence of their p53 status.
Materials and methods.
Three pairs of tumour cell lines were used, each consisting of one p53 functional and one p53 non-functional line. Cells were labelled with bromodeoxyuridine(BrdU) immediately after irradiation, they were then incubated in label-free medium, and at different times afterwards their position within the S-phase was determined by means of flow cytometry.
Results
While in the p53 deficient cells progression through S-phase was slowed significantly over at least a few hours, it was halted for just about an hour in the p53 proficient cells and then proceeded without further delay or even at a slightly accelerated pace.
Conclusions
It is clear from the experiments presented here that p53 does play a role for the progress of cells through the S-phase after X-ray exposure, but the exact mechanisms by which replicon initiation and elongation is controlled in irradiated cells remain to be elucidated.
doi:10.2478/raon-2014-0032
PMCID: PMC4230555  PMID: 25435848
x-rays; intra-S-phase checkpoint; flow cytometry, relative movement
5.  Intercalated chemotherapy and erlotinib for advanced NSCLC: high proportion of complete remissions and prolonged progression-free survival among patients with EGFR activating mutations 
Radiology and Oncology  2014;48(4):361-368.
Background
Pharmaco-dynamic separation of cytotoxic and targeted drugs might avoid their mutual antagonistic effect in the treatment of advanced non-small cell lung cancer (NSCLC).
Patients and methods.
Eligible patients were treatment-naive with stage IIIB or IV NSCLC. In addition, inclusion was limited to never-smokers or light smokers or, after 2010, to patients with activating epidermal growth-factor receptor (EGFR) mutations. Treatment started with 3-weekly cycles of gemcitabine and cisplatin on days 1, 2 and 4 and erlotinib on days 5 to 15. After 4 to 6 cycles, patients continued with erlotinib maintenance.
Results
Fifty-three patients were recruited into the trial: 24 prior to 2010 (of whom 9 were later found to be positive for EGFR mutations), and 29 EGFR mutation-positive patients recruited later. Unfavourable prognostic factors included stage IV disease (51 patients - 96%), performance status 2–3 (11 patients - 21%) and brain metastases (15 patients -28%). Grade 4 toxicity included 2 cases of neutropenia and 4 thrombo-embolic events. The 15 EGFR negative patients had 33% objective response rate, median progression-free survival (PFS) 6.0 months and median survival 7.6 months. Among 38 EGFR positive patients, complete response (CR) or partial response (PR) were seen in 16 (42.1%) and 17 (44.7%) cases, respectively. PET-CT scanning was performed in 30 patients and confirmed CR and PR in 16 (53.3%) and 9 (30.0%) cases, respectively. Median PFS for EGFR mutated patients was 21.2 months and median survival was 32.5 months.
Conclusions
While patients with EGFR negative tumors do not benefit from addition of erlotinib, the intercalated schedule appears most promising for those with EGFR activating mutations.
doi:10.2478/raon-2014-0038
PMCID: PMC4230556  PMID: 25435849
Non-small cell lung cancer; EGFR activating mutations; gemcitabine; cisplatin; erlotinib; intercalated therapy; metabolic response
6.  Induction gemcitabine in standard dose or prolonged low-dose with cisplatin followed by concurrent radiochemotherapy in locally advanced non-small cell lung cancer: a randomized phase II clinical trial 
Radiology and Oncology  2014;48(4):369-380.
Background
The optimal combination of chemotherapy with radiation therapy for treatment locally advanced non-small cell lung cancer (NSCLC) remains an open issue. This randomized phase II study compared gemcitabine in two different schedules and cisplatin - as induction chemotherapy, followed by radiation therapy concurrent with cisplatin and etoposid.
Patients and methods.
Eligible patients had microscopically confirmed inoperable non-metastatic non-small cell lung cancer; fulfilled the standard criteria for platin-based chemotherapy; and signed informed consent. Patients were treated with 3 cycles of induction chemotherapy with gemcitabine and cisplatin. Two different aplications of gemcitabine were compared: patients in arm A received gemcitabine at 1250 mg/m2 in a standard half hour i.v. infusion on days 1 and 8; patients in arm B received gemcitabine at 250 mg/m2 in prolonged 6-hours i.v. infusion on days 1 and 8. In both arms, cisplatin 75 mg/m2 on day 2 was administered. All patients continued treatment with radiation therapy with 60–66 Gy concurrent with cisplatin 50 mg/m2 on days 1, 8, 29 and 36 and etoposid 50 mg/m2 on days 1–5 and 29–33. The primary endpoint was response rate (RR) after induction chemotherapy; secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS).
Results
From September 2005 to November 2010, 106 patients were recruited to this study. No statistically signifficant differences were found in RR after induction chemotherapy between the two arms (48.1% and 57.4%, p = 0.34). Toxicity profile was comparable and mild with grade 3/4 neutropenia as primary toxicity in both arms. One patient in arm B suffered from acute peripheral ischemia grade 4 and an amputation of lower limb was needed. With a median follow-up of 69.3 months, progression-free survival and median survival in arm A were 15.7 and 24.8 months compared to 18.9 and 28.6 months in arm B. The figures for 1- and 3-year overall survival were 73.1% and 30.8% in arm A, and 81.5 % and 44.4% in arm B, respectively.
Conclusions
Among the two cisplatin-based doublets of induction chemotherapy for inoperable NSCLC, both schedules of gemcitabine have a comparable toxicity profile. Figures for RR, PFS and OS are among the best reported in current literature. While there is a trend towards better efficacy of the treament with prolonged infusion of gemcitabine, the difference between the two arms did not reach statistical significance.
PMCID: PMC4230557  PMID: 25435850
induction chemotherapy; gemcitabine; non-small cell lung cancer; radiation therapy; concurrent chemoradiation; randomized clinical trial
7.  Survival of patients treated with radiation therapy for anaplastic astrocytoma 
Radiology and Oncology  2014;48(4):381-386.
Background
Anaplastic astrocytoma (AA) represents 7% of primary brain tumors in adults. Patient-, tumor-, and treatment-related factors are thought to be predictive of survival. We retrospectively assessed the association of patient-, tumor-, and treatment-related factors with survival in AA treated with radiotherapy (RT) at our institution.
Patients and methods.
Medical records of patients with AA treated with RT between 1987 and 2007 were reviewed. Patient-, tumor-, and treatment-related variables were recorded and used to assign patients to a Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) classification. First use of chemotherapy was recorded. Log-rank tests and Cox regression models were used to assess for an association of patient-, tumor- and treatment-related factors with survival.
Results
One-hundred twenty-six patients were eligible for study. Median age, Karnofsky performance status, and duration of symptoms were 43 years, 90, and 8 weeks. Median radiation dose was 59.4 Gy; 61% of patients underwent tumor resection, and 17% and 41% of patients received temozolomide during and after RT. Median survival was 31 months, and 2-year survival was 58%. RTOG RPA class was associated with survival (p < 0.001), but use of temozolomide during or after RT was not (p > 0.05).
Conclusions
In this retrospective study with inherent limitations, RTOG RPA classification was associated with survival. Further studies are necessary to confirm or refute this finding.
doi:10.2478/raon-2014-0019
PMCID: PMC4230558  PMID: 25435851
anaplastic astrocytoma; radiation therapy; prognosis; Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA); temozolomide (TMZ); chemoradiation therapy
8.  Identification of three anatomical patterns of the spinal accessory nerve in the neck by neurophysiological mapping 
Radiology and Oncology  2014;48(4):387-392.
Background
In spite of preservation of the accessory nerve there is still considerable proportion of patients with partial nerve damage during modified radical neck dissection (MRND).
Methods
The nerve was identified during the surgery and its branches for the trapezius muscle mapped with nerve monitor.
Results
The accessory nerve was mapped during 74 hemineck dissections and three patterns were identified. In type 1 nerve exits at the posterior end of the sternocleidomastoid muscle (SCm) and then it enters the level V (66%). In type 2 the nerve for trapezius muscle branches off before entering the SCm (22%). In type 3 the nerve exits at the posterior part of the SCm and it joins to the cervical plexus (12%). The nerve than exits this junction more medially as a single trapezius branch.
Conclusions
The description of three anatomical patterns in level II and V could help preserving the trapezius branch during MRND.
doi:10.2478/raon-2013-0069
PMCID: PMC4230559  PMID: 25435852
spinal accessory nerve; nerve mapping; neck dissection; anatomy; shoulder disability
9.  Distant metastasis of rectal adenocarcinoma in a temporary tracheostoma 
Radiology and Oncology  2014;48(4):393-396.
Background
The temporary tracheostoma’s metastases of head and neck cancer had already been reported in the literature. So far, they had been considered as regional dissemination of the malignant disease. We report a case of temporary tracheostoma’s metastasis of carcinoma from non-head-and-neck primary site, what has not been reported in the literature, yet. Therefore, it is the first reported case of the systemic dissemination of malignant tumour into temporary tracheostoma.
Case report.
Fifty-four-year-old female patient, previously treated for a rectal adenocarcinoma, reported in our office with exophytic pink tissue masses around the temporary tracheostoma. The biopsy and immunohistochemistry findings were consistent with temporary tracheostoma’s metastasis of the rectal adenocarcinoma. The patient received palliative radiotherapy and died of systemic progression of the disease.
Conclusions
The patients with history of primary cancer of any origin and exophytic proliferating changes around the tracheostoma require an appropriate diagnostic work-up including a biopsy. The type of treatment depends on the extent of the disease, previous therapy and general condition of the patient.
doi:10.2478/raon-2013-0079
PMCID: PMC4230560  PMID: 25435853
temporary tracheostoma; distant metastasis; rectal adenocarcinoma
10.  Mediastinal teratoma with hydrops fetalis in a newborn and development of chronic respiratory insufficiency 
Radiology and Oncology  2014;48(4):397-402.
Background
Mediastinal fetal teratoma can be detected as a mass in the chest during a routine prenatal ultra-sound screening. Because of the pressure on mediastinal structures it can be the cause of non-immune hydrops fetalis and polyhydramnion. The development of hydrops fetalis leads to fetal death or premature delivery in most reported cases. Early surgical removal is important, but, the result of treatment depends on the stage of development of mediastinal organs and complications in the postoperative period.
Case report.
A 31-year-old gravida carrying twins, with spontaneous membrane rupture at 32 weeks gestation underwent urgent caesarean section after antenatal ultrasound revealed severe polyhydramnion and hydrops fetalis in geminus A. The child was intubated immediately after birth due to severe respiratory distress. Ultrasound and X-ray revealed a tumour mass in the right hemithorax. Tumour resection was performed at the age of 7 days. Histology examination revealed an encapsulated immature teratoma. The postoperative course was complicated with respiratory insufficiency which turned into chronic at the age of eight months.
Conclusion
This is the fifth reported child with fetal mediastinal teratoma and severe hydrops fetalis that survived the neonatal period. Additional diagnostic search revealed abnormal course of both pulmonary arteries, which was probably one of the main causes of respiratory insufficiency.
doi:10.2478/raon-2013-0080
PMCID: PMC4230561  PMID: 25435854
mediastinal teratoma; non-immune hydrops fetalis; diaphragm paralysis; chronic respiratory insufficiency
11.  Effectiveness of adjuvant trastuzumab in daily clinical practice 
Radiology and Oncology  2014;48(4):403-407.
Background
Human epidermal growth factor receptor 2 (HER2) positive breast cancer is an entity with aggressive behaviour. One year of adjuvant trastuzumab significantly improves the disease free survival in the range of 40–50% and reduces the risk of dying from HER2 positive breast cancer by one third. Adjuvant treatment with trastuzumab became available in Slovenia in 2005 and the aim of this study is to explore, if the exceptional results reported in adjuvant clinical trials are achieved also in daily clinical practice.
Patients and methods.
An analysis of tumour and patient characteristics, type of treatment and outcome (relapse free and overall survival) of 313 patients (median age 52 years) treated at the Institute of Oncology Ljubljana in years 2005–2009 was performed.
Results
Median follow-up was 4.4 years. Sixty-one patients relapsed and 24 died. Three and four years relapse free survival was 84.2% and 80.8% and the overall survival was 94.4% and 92.5%, respectively. Independent prognostic factors for relapse were tumour grade (HR 2.10; 95% CI 1.07–4.14; p = 0.031) and nodal stage (HR 1.35; 1.16–1.56; p < 0.0001) and for the overall survival nodal stage only (HR 1.36; 1.05–1.78; p = 0.021).
Conclusions
The outcome in patients with adjuvant trastuzumab in daily clinical practice, treated by medical oncologists, is comparable to results obtained in international adjuvant studies.
doi:10.2478/raon-2013-0081
PMCID: PMC4230562  PMID: 25435855
breast cancer; trastuzumab, adjuvant; daily clinical practice
12.  A method for generating large datasets of organ geometries for radiotherapy treatment planning studies 
Radiology and Oncology  2014;48(4):408-415.
Background
With the rapidly increasing application of adaptive radiotherapy, large datasets of organ geometries based on the patient’s anatomy are desired to support clinical application or research work, such as image segmentation, re-planning, and organ deformation analysis. Sometimes only limited datasets are available in clinical practice. In this study, we propose a new method to generate large datasets of organ geometries to be utilized in adaptive radiotherapy.
Methods
Given a training dataset of organ shapes derived from daily cone-beam CT, we align them into a common coordinate frame and select one of the training surfaces as reference surface. A statistical shape model of organs was constructed, based on the establishment of point correspondence between surfaces and non-uniform rational B-spline (NURBS) representation. A principal component analysis is performed on the sampled surface points to capture the major variation modes of each organ.
Results
A set of principal components and their respective coefficients, which represent organ surface deformation, were obtained, and a statistical analysis of the coefficients was performed. New sets of statistically equivalent coefficients can be constructed and assigned to the principal components, resulting in a larger geometry dataset for the patient’s organs.
Conclusions
These generated organ geometries are realistic and statistically representative.
doi:10.2478/raon-2014-0003
PMCID: PMC4230563  PMID: 25435856
non-uniform rational B-spline technique; new geometries; statistical shape model; adaptive radiotherapy
13.  Slovenian experience from diagnostic angiography to interventional radiology 
Radiology and Oncology  2014;48(4):416-425.
Background
The purpose of writing this article is to document the important events and people in the first 50 years of diagnostic angiography and interventional radiology in Slovenia. During this period not only did the name of the institutions and departments change, but also its governance.
Conclusions
This depicted the important roles different people played at various times in the cardiovascular divisions inside and outside of the diagnostic and interventional radiology. Historical data show that Slovenian radiology has relatively immediately introduced the new methods of interventional radiology in clinical practice.
doi:10.2478/raon-2014-0023
PMCID: PMC4230564  PMID: 25435857
diagnostic angiography; interventional radiology; history
14.  The role of fluorine-18-fluorodeoxyglucose positron emission tomography in evaluating the response to tyrosine-kinase inhibitors in patients with metastatic primary renal cell carcinoma 
Radiology and Oncology  2014;48(3):219-227.
Background
Positron emission tomography-computed tomography (PET-CT) using fluorodeoxyglucose (FDG) is increasingly used in the evaluation of patients with advanced renal cell carcinoma (RCC), primarily for staging purposes. The aim of this paper is to perform a systematic review about the usefulness of PET-CT using FDG in response assessment after treatment with tyrosine-kinase inhibitors (TKIs) in patients with advanced RCC.
Materials and methods.
The scientific literature about the role of PET-CT using FDG in the assessment of response to treatment with TKIs in patients affected by advanced RCC was systematically reviewed.
Results
Seven studies about the role of PET-CT using FDG in the response assessment after treatment with TKIs (essentially sunitinib and sorafenib) in advanced RCC were retrieved in full-text and analysed, to determine the predictive role of this morpho-functional imaging method on patient outcome.
Conclusions
To date, the role of PET-CT using FDG in evaluating the response to TKIs in metastatic RCC patients is still not well defined, partly due to heterogeneity of available studies; however, PET-CT reveals potential role for the selection of patients undergoing therapy with TKIs. The use of contrast-enhanced PET-CT appears to be promising for a “multi-dimensional” evaluation of treatment response in these patients.
doi:10.2478/raon-2013-0067
PMCID: PMC4110077  PMID: 25177235
fluorodeoxyglucose; positron emission tomography; advanced renal cell carcinoma; tyrosine-kinase inhibitors; response to treatment
15.  Incidental uptake of 18F-fluorocholine (FCH) in the head or in the neck of patients with prostate cancer 
Radiology and Oncology  2014;48(3):228-234.
Background
Positron emission tomography-computed tomography (PET/CT) with 18F-fluorocholine (FCH) is routinely performed in patients with prostate cancer. In this clinical context, foci of FCH uptake in the head or in the neck were considered as incidentalomas, except for those suggestive of multiple bone metastases.
Results
In 8 patients the incidental focus corresponded to a benign tumour. The standard of truth was histology in two cases, correlative imaging with MRI in four cases, 99mTc-SestaMIBI scintigraphy, ultrasonography and biochemistry in one case and biochemistry including PTH assay in one case. The final diagnosis of benign tumours consisted in 3 pituitary adenomas, 2 meningiomas, 2 hyperfunctioning parathyroid glands and 1 thyroid adenoma.
Malignancy was proven histologically in 2 other patients: 1 papillary carcinoma of the thyroid and 1 cerebellar metastasis.
Conclusions
To the best of our knowledge, FCH uptake by pituitary adenomas or hyperfunctioning parathyroid glands has never been described previously. We thus discuss whether there might be a future indication for FCH PET/CT when one such tumour is already known or suspected: to detect a residual or recurrent pituitary adenoma after surgery, to guide surgery or radiotherapy of a meningioma or to localise a hyperfunctioning parathyroid gland. In these potential indications, comparative studies with reference PET tracers or with 99mTc-sestaMIBI in case of hyperparathyroidism could be undertaken.
doi:10.2478/raon-2013-0075
PMCID: PMC4110078  PMID: 25177236
FCH, PET/CT; incidentaloma; meningioma; pituitary adenoma; hyperparathyroidism; thyroid adenoma
16.  Clinical and radiologic features of extraskeletal myxoid chondrosarcoma including initial presentation, local recurrence, and metastases 
Radiology and Oncology  2014;48(3):235-242.
Background
The aim of the study was to evaluate the clinical and imaging features of extraskeletal myxoid chondrosarcoma (EMC) including initial presentation, recurrence, and metastases.
Patients and methods.
In this institutional review board-approved retrospective study, imaging features of 13 patients with pathologically proven EMC seen from August 1995 to December 2011 were analyzed. The group included 3 women and 10 men and the mean age was 54 years (range 29–73 years). Imaging studies were evaluated by two radiologists in consensus. Location, size, and imaging features of primary tumors were recorded as well as the presence of recurrent disease and location of metastases.
Results
Among 13 patients, 3 died during the timeframe of this study. Nine patients had primary tumor in the lower extremity, and average tumor size was 9.3 cm (range 3.3–18 cm). On MRI, primary tumors were hyperintense on T2, isointense to muscle on T1, and demonstrated peripheral/septal enhancement. Three patients had local recurrence and 12 had metastatic disease, with lung involvement being the most common. Tumor density on contrast enhanced CT ranged from 8.2 to 82.9 Hounsfield unit (HU). FDG-PET/CT imaging was performed in 3 patients. One patient had no FDG avid disease and 2 patients had metastatic disease with standard uptake values (SUV) of 2.8 and 7.4. The patient with intense FDG uptake demonstrated more solid appearing tumor burden and had the shortest survival.
Conclusions
EMC is a rare tumor that often occurs in the lower extremities and frequently metastasizes to the lungs. Increased tumor density and increased FDG uptake may be related to more aggressive disease.
doi:10.2478/raon-2014-0005
PMCID: PMC4110079  PMID: 25177237
extraskeletal myxoid chondrosarcoma; CT; MRI; FDG-PET/CT
17.  Osteoblastic bone metastases from renal cell carcinoma 
Radiology and Oncology  2014;48(3):243-246.
Background
RCC accounts for only 2–3% of all cancers. Due to its’ non-specific symptoms disease is often diagnosed in advanced stage. Disseminated RCC frequently produces bone metastases that are almost always highly destructive, hyper vascularized and purely osteolytic.
Case report.
In this article we describe a case of a 71-year old male patient with disseminated osteoblastic bone metastases from renal cell carcinoma (RCC), and present a short review of published literature reporting cases of osteoblastic bone metastases from RCC. Our patient presented with thoracic pain aggravated by movement. He was diagnosed with predominantly osteoblastic bone metastases in the skeleton of thoracic and lumbar vertebra along with metastases in iliac bones, ribs, humerus and clavicles. Initially, origin of bone metastases was unknown, but later a small tumor in patient’s right kidney was identified. Microscopic evaluation of the open bone biopsy showed clear cell RCC with sarcomatoid differentiation.
Conclusions
Although, due to its’ rarity, RCC is not included in the primary differential diagnosis in patients with osteoblastic metastases, such rare cases suggest that RCC may be considered in the diagnosis when there no other primary tumor is found.
doi:10.2478/raon-2013-0034
PMCID: PMC4110080  PMID: 25177238
renal cell carcinoma; osteoblastic bone metastases
18.  The effect of radiation dose on mouse skeletal muscle remodeling 
Radiology and Oncology  2014;48(3):247-256.
Background
The purpose of this study was to determine the effect of two clinically relevant radiation doses on the susceptibility of mouse skeletal muscle to remodeling.
Materials and methods.
Alterations in muscle morphology and regulatory signaling were examined in tibialis anterior and gastrocnemius muscles after radiation doses that differed in total biological effective dose (BED). Female C57BL/6 (8-wk) mice were randomly assigned to non-irradiated control, four fractionated doses of 4 Gy (4x4 Gy; BED 37 Gy), or a single 16 Gy dose (16 Gy; BED 100 Gy). Mice were sacrificed 2 weeks after the initial radiation exposure.
Results
The 16 Gy, but not 4x4 Gy, decreased total muscle protein and RNA content. Related to muscle regeneration, both 16 Gy and 4x4 Gy increased the incidence of central nuclei containing myofibers, but only 16 Gy increased the extracellular matrix volume. However, only 4x4 Gy increased muscle 4-hydroxynonenal expression. While both 16 Gy and 4x4 Gy decreased IIB myofiber mean cross-sectional area (CSA), only 16 Gy decreased IIA myofiber CSA. 16 Gy increased the incidence of small diameter IIA and IIB myofibers, while 4x4 Gy only increased the incidence of small diameter IIB myofibers. Both treatments decreased the frequency and CSA of low succinate dehydrogenase activity (SDH) fibers. Only 16 Gy increased the incidence of small diameter myofibers having high SDH activity. Neither treatment altered muscle signaling related to protein turnover or oxidative metabolism.
Conclusions
Collectively, these results demonstrate that radiation dose differentially affects muscle remodeling, and these effects appear to be related to fiber type and oxidative metabolism.
doi:10.2478/raon-2014-0025
PMCID: PMC4110081  PMID: 25177239
extracellular matrix; irradiation; oxidative metabolism; regeneration; skeletal muscle
19.  Identification of plasma biomarker candidates in glioblastoma using an antibody-array-based proteomic approach 
Radiology and Oncology  2014;48(3):257-266.
Background
Glioblastoma multiforme (GBM) is a brain tumour with a very high patient mortality rate, with a median survival of 47 weeks. This might be improved by the identification of novel diagnostic, prognostic and predictive therapy-response biomarkers, preferentially through the monitoring of the patient blood. The aim of this study was to define the impact of GBM in terms of alterations of the plasma protein levels in these patients.
Materials and methods.
We used a commercially available antibody array that includes 656 antibodies to analyse blood plasma samples from 17 healthy volunteers in comparison with 17 blood plasma samples from patients with GBM.
Results
We identified 11 plasma proteins that are statistically most strongly associated with the presence of GBM. These proteins belong to three functional signalling pathways: T-cell signalling and immune responses; cell adhesion and migration; and cell-cycle control and apoptosis. Thus, we can consider this identified set of proteins as potential diagnostic biomarker candidates for GBM. In addition, a set of 16 plasma proteins were significantly associated with the overall survival of these patients with GBM. Guanine nucleotide binding protein alpha (GNAO1) was associated with both GBM presence and survival of patients with GBM.
Conclusions
Antibody array analysis represents a useful tool for the screening of plasma samples for potential cancer biomarker candidates in small-scale exploratory experiments; however, clinical validation of these candidates requires their further evaluation in a larger study on an independent cohort of patients.
doi:10.2478/raon-2014-0014
PMCID: PMC4110082  PMID: 25177240
glioblastoma; proteomics; biomarker; antibody array; plasma
20.  Segmentation of hepatic vessels from MRI images for planning of electroporation-based treatments in the liver 
Radiology and Oncology  2014;48(3):267-281.
Introduction.
Electroporation-based treatments rely on increasing the permeability of the cell membrane by high voltage electric pulses delivered to tissue via electrodes. To ensure that the whole tumor is covered by the sufficiently high electric field, accurate numerical models are built based on individual patient geometry. For the purpose of reconstruction of hepatic vessels from MRI images we searched for an optimal segmentation method that would meet the following initial criteria: identify major hepatic vessels, be robust and work with minimal user input.
Materials and methods.
We tested the approaches based on vessel enhancement filtering, thresholding, and their combination in local thresholding. The methods were evaluated on a phantom and clinical data.
Results
Results show that thresholding based on variance minimization provides less error than the one based on entropy maximization. Best results were achieved by performing local thresholding of the original de-biased image in the regions of interest which were determined through previous vessel-enhancement filtering. In evaluation on clinical cases the proposed method scored in average sensitivity of 93.68%, average symmetric surface distance of 0.89 mm and Hausdorff distance of 4.04 mm.
Conclusions
The proposed method to segment hepatic vessels from MRI images based on local thresholding meets all the initial criteria set at the beginning of the study and necessary to be used in treatment planning of electroporation-based treatments: it identifies the major vessels, provides results with consistent accuracy and works completely automatically. Whether the achieved accuracy is acceptable or not for treatment planning models remains to be verified through numerical modeling of effects of the segmentation error on the distribution of the electric field.
doi:10.2478/raon-2014-0022
PMCID: PMC4110083  PMID: 25177241
electrochemotherapy; non-thermal irreversible electroporation; treatment planning; hepatic vessel segmentation; non-invasive tumor treatments; MRI of liver
21.  Microinvasive cervical squamous cell carcinoma in Slovenia during the period 2001–2007 
Radiology and Oncology  2014;48(3):282-288.
Background
Microinvasive squamous cell carcinoma (MISCC) comprises a significant portion of all cervical cancers in Slovenia. Criteria of carcinomatous invasion are well described in the literature, however histopathological assessment of MISCC is difficult, because morphological characteristics can overlap with cervical intraepithelial neoplasia grade 3 (CIN 3) and other pathological changes. The aim of our study was to evaluate the reliability of the histopathological diagnosis of MISCC in Slovenia during the period from 2001 to 2007.
Materials and methods.
Data on patients with a histopathological diagnosis of cervical MISCC (FIGO stage IA) in the period of 2001 to 2007 were obtained from the Cancer Registry of Slovenia. Histological slides were obtained from the majority of pathology laboratories in Slovenia. We received 250 cases (69% of all MISCC) for the review; 30 control cases with CIN 3 and invasive squamous cell carcinoma FIGO stage IB were intermixed. The slides were coded and reviewed.
Results
Among 250 cases originally diagnosed as MISCC, there was an agreement with MISCC diagnosis in 184 (73.6%) cases (of these 179/184 (97.3%) cases were FIGO stage IA1 and 5/184 (2.7%) cases were FIGO stage IA2). Among 179 FIGO stage IA1 cases 117 (65.4%) showed only early stromal invasion.
Conclusions
The retrospective review of cases diagnosed as MISCC during the period 2001–2007 in Slovenia showed a considerable number of overdiagnosed cases. Amongst cases with MISCC confirmed on review, there was a significant proportion with early stromal invasion (depth of invasion less than 1 mm).
doi:10.2478/raon-2014-0010
PMCID: PMC4110084  PMID: 25177242
cervical cancer; cervical squamous cell carcinoma; microinvasive squamous cell carcinoma; cervical intraepithelial neoplasia
22.  The influence of folate pathway polymorphisms on high-dose methotrexate-related toxicity and survival in children with non-Hodgkin malignant lymphoma 
Radiology and Oncology  2014;48(3):289-292.
Background
We evaluated the influence of folate pathway polymorphisms on high-dose methotrexate (HD-MTX) related toxicity in paediatric patients with T-cell non-Hodgkin lymphoma (NHL).
Patients and methods
In total, 30 NHL patients were genotyped for selected folate pathway polymorphisms.
Results
Carriers of at least one MTHFR 677T allele had significantly higher MTX area under the time-concentration curve levels at third MTX cycle (P = 0.003). These patients were also at higher odds of leucopoenia (P = 0.006) or thrombocytopenia (P = 0.041) and had higher number of different HD-MTX-related toxicity (P = 0.035) compared to patients with wild-type genotype.
Conclusions
Our results suggest an important role of MTHFR 677C>T polymorphism in the development of HD-MTX-related toxicity in children with NHL.
doi:10.2478/raon-2013-0076
PMCID: PMC4110085  PMID: 25177243
childhood; non-Hodgkin lymphoma; folate pathway; polymorphism; high-dose methotrexate; toxicity
23.  MRI-assisted cervix cancer brachytherapy pre-planning, based on application in paracervical anaesthesia: final report 
Radiology and Oncology  2014;48(3):293-300.
Background
Optimal applicator insertion is a precondition for the success of cervix cancer brachytherapy (BT). We aimed to assess feasibility and efficacy of MRI-assisted pre-planning, based on applicator insertion in para-cervical anaesthesia (PCA).
Patients and methods.
Five days prior to BT, the pre-planning procedure was performed in 18 cervix cancer patients: tandem-ring applicator was inserted under PCA, pelvic MRI obtained and applicator removed. Procedure tolerability was assessed. High risk clinical target volume (HR CTV) and organs at risk were delineated on the pre-planning MRI, virtual needles placed at optimal positions, and dose planning performed. At BT, insertion was carried out in subarachnoidal anaesthesia according to pre-planned geometry. Pre-planned and actual treatment parameters were compared.
Results
Pre-planning procedure was well tolerated. Median difference between the pre-planned and actual needle insertion depth and position were 2 (0–10) mm and 4 (0–30) degrees, respectively. The differences between the pre-planned and actual geometric and dosimetric parameters were statistically non-significant. All actual needles were positioned inside the HR CTV and outside the organs at risk (OAR).
Conclusions
Our pre-planning approach is well tolerated and effective. Pre-planned geometry and dose distribution can be reproduced at BT.
doi:10.2478/raon-2014-0009
PMCID: PMC4110086  PMID: 25177244
cervix cancer; MRI; pre-planning; image-guided brachytherapy
24.  Olfaction and gustation abilities after a total laryngectomy 
Radiology and Oncology  2014;48(3):301-306.
Background
A laryngectomy affects many of a patient’s functions. Besides speech and respiratory-tract problems, olfaction and gustation problems can also have an influence on the quality of life. The aim of this study was to find out how often various nasal problems and decreased gustation appear after a laryngectomy.
Patients and methods.
One hundred and five laryngectomized patients (9 women, 96 men, aged 45–88 years), treated in two tertiary centers, were included in the study. They completed a questionnaire about various nasal problems, olfactory and gustatory capabilities, possible allergies and irritants in their environment, and the impact of the nasal and gustation problems on their quality of life.
Results
Olfaction was impaired in 51.4%, and was even not possible in 30.5%, of patients. Decreased gustation abilities were reported in 26.7%, and dysgeusia in 11.4%, of patients. Almost 21% of patients were bothered by an impaired gustatory ability and 50.5% of patients were affected by their loss of olfaction. Frequent nasal discharge was reported in 20%, frequent sneezing in 58.1%, and nasal itching in 33.3% of the laryngectomized patients. There were no correlations between the age and the olfaction and gustation abilities and between the allergy and the nasal symptoms, whereas the correlation between olfaction and gustation appeared significant (p=0.025).
Conclusions
Various nasal and gustatory problems were reported in more than 80% of laryngectomized patients. The olfaction and gustation abilities are connected and have a substantial impact on the quality of life. Like in the case of speech, the rehabilitation of olfaction is also necessary in all laryngectomized patients and must take place soon after the completion of the treatment.
doi:10.2478/raon-2013-0070
PMCID: PMC4110087  PMID: 25177245
laryngectomy; olfaction; gustation; questionnaire; quality of life
25.  Circulating serum sVCAM-1 concentration in advanced ovarian cancer patients: correlation with concentration in ascites 
Radiology and Oncology  2014;48(3):307-313.
Background
Vascular cell adhesion molecule-1 (VCAM-1) is associated with ovarian cancer progression but the origin of its soluble form (sVCAM-1) in serum is not well investigated. The purpose of this study was to elucidate whether the concentration of sVCAM-1 in serum correlates with the concentration in ascites, that represents local tumour environment, and with systemic inflammation, various clinicopathological characteristics, and patient outcome.
Patients and methods.
Thirty-six patients with advanced ovarian cancer were included in the study. Serum for sVCAM-1 analysis was obtained prior to surgery. Ascites samples were collected at the beginning of the operation. Clinical data were collected from patients’ medical records. sVCAM-1 in samples was analysed by flow cytometric bead-based assay. The mean follow-up period was 11 months (range 0–23) from the time of surgery.
Results
Serum sVCAM-1 concentrations are positively correlated to ascites sVCAM-1 concentrations. There was a weakly positive correlation of serum sVCAM-1 with tumour size and no correlation with inflammatory tumour markers, FIGO stage or grade. Higher concentrations of sVCAM-1 were associated with poor disease outcome (death from ovarian cancer) in almost all cases before chemotherapy was started.
Conclusions
This is the first study demonstrating that serum concentrations of sVCAM-1 in advanced ovarian cancer patients correlate with sVCAM-1 concentrations in ascites, thus expressing the biologic potential of malignant disease to metastasis, rather than systemic inflammation. Higher serum and ascites sVCAM-1 concentrations might have predictive potential for different biologic behaviour.
doi:10.2478/raon-2013-0066
PMCID: PMC4110088  PMID: 25177246
sVCAM-1; ovarian cancer; flow cytometry

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