rss_2.0Radiology and Oncology FeedSciendo RSS Feed for Radiology and Oncology and Oncology 's Cover plus letrozole in patients with hormone receptor-positive, HER2-negative advanced breast cancer with no prior endocrine therapy: subgroup safety analysis from the phase 3b CompLEEment-1 trial<abstract> <title style='display:none'>Abstract</title> <sec id="j_raon-2022-0020_s_007"><title style='display:none'>Background</title> <p>The CDK4/6 inhibitor, ribociclib in combination with endocrine therapy significantly improved progression-free survival in the first line setting in post-menopausal patients with HR+/HER2− advanced breast cancer (ABC) in a pivotal phase 3, placebo-controlled trial (MONALEESA-2) and demonstrated superior overall survival in premenopausal patients with HR+/HER2− ABC (MONALEESA-7). The multinational, phase 3b, CompLEEment-1 trial, which assessed the safety and efficacy of ribociclib plus letrozole in a broader population of patients who have not received prior endocrine therapy for advanced disease, is the largest phase 3 clinical trial to date to evaluate the safety and efficacy of a CDK4/6 inhibitor. We report a subanalysis of data from patients (N = 339) enrolled in the central and south European countries of the SERCE (Southern Europe, RUC, Central Europe) cluster of CompLEEment-1.</p></sec> <sec id="j_raon-2022-0020_s_008"><title style='display:none'>Patients and methods</title> <p>Men and women of any menopausal status with HR+/HER2− ABC received once-daily oral ribociclib 600 mg (3-weeks on/1-week-off), plus letrozole 2.5 mg continuously. Men/premenopausal women also received a GnRH-agonist. The primary outcome was the number of patients with adverse events (AEs) over a timeframe of approximately 36 months. Time-to-progression, overall response rate, and clinical benefit rate were also measured.</p></sec> <sec id="j_raon-2022-0020_s_009"><title style='display:none'>Results</title> <p>Safety results in the SERCE subgroup were consistent with those in the pivotal clinical trials of ribociclib in combination with endocrine therapy. Treatment-related AEs leading to dose adjustments/interruption occurred in 63.1% of patients but led to treatment discontinuation in only 10.6%. The most common treatment-related AEs of grade ≥ 3 were neutropenia and transaminase elevations. There were no fatal treatment-related events.</p></sec> <sec id="j_raon-2022-0020_s_010"><title style='display:none'>Conclusions</title> <p>These findings from the SERCE subgroup support the safety and manageable tolerability of ribociclib in a broad range of patients with HR+/HER2− ABC more representative of patients in real-world clinical practice.</p></sec> </abstract>ARTICLE2022-05-17T00:00:00.000+00:00The dose accumulation and the impact of deformable image registration on dose reporting parameters in a moving patient undergoing proton radiotherapy<abstract> <title style='display:none'>Abstract</title> <sec id="j_raon-2022-0016_s_006"><title style='display:none'>Introduction</title> <p>Potential changes in patient anatomy during proton radiotherapy may lead to a deviation of the delivered dose. A dose estimate can be computed through a deformable image registration (DIR) driven dose accumulation. The present study evaluates the accumulated dose uncertainties in a patient subject to an inadvertent breathing associated motion.</p></sec> <sec id="j_raon-2022-0016_s_007"><title style='display:none'>Materials and methods</title> <p>A virtual lung tumour was inserted into a pair of single participant landmark annotated computed tomography images depicting opposite breathing phases, with the deep inspiration breath-hold the planning reference and the exhale the off-reference geometry. A novel Monte Carlo N-Particle, Version 6 (MCNP6) dose engine was developed, validated and used in treatment plan optimization. Three DIR methods were compared and used to transfer the exhale simulated dose to the reference geometry. Dose conformity and homogeneity measures from International Committee on Radioactivity Units and Measurements (ICRU) reports 78 and 83 were evaluated on simulated dose distributions registered with different DIR algorithms.</p></sec> <sec id="j_raon-2022-0016_s_008"><title style='display:none'>Results</title> <p>The MCNP6 dose engine handled patient-like geometries in reasonable dose calculation times. All registration methods were able to align image associated landmarks to distances, comparable to voxel sizes. A moderate deterioration of ICRU measures was encountered in comparing doses in on and off-reference anatomy. There were statistically significant DIR driven differences in ICRU measures, particularly a 10% difference in the relative D<sub>98%</sub> for planning tumour volume and in the 3 mm/3% gamma passing rate.</p></sec> <sec id="j_raon-2022-0016_s_009"><title style='display:none'>Conclusions</title> <p>T he dose accumulation over two anatomies resulted in a DIR driven uncertainty, important in reporting the associated ICRU measures for quality assurance.</p></sec> </abstract>ARTICLE2022-05-17T00:00:00.000+00:00Safety and efficacy of drug-eluting microspheres chemoembolization under cone beam computed tomography control in patients with early and intermediate stage hepatocellular carcinoma<abstract> <title style='display:none'>Abstract</title> <sec id="j_raon-2022-0019_s_005"><title style='display:none'>Background</title> <p>Drug-eluting microsphere transarterial chemoembolization (DEM-TACE) is the standard of care in patients with intermediate-stage hepatocellular carcinoma and ensures targeted and controlled cytotoxic and ischemic effects. Proper patient selection and optimized treatment techniques are associated with longer median survival. The aim of this single-institution retrospective study was to evaluate safety and efficacy of DEM-TACE under cone beam computed tomography (CBCT) control in patients with early and intermediate stage hepatocellular carcinoma.</p></sec> <sec id="j_raon-2022-0019_s_006"><title style='display:none'>Patients and methods</title> <p>A total of 144 patients (mean age 67.9 ± 8.0 years, 127 males and 17 females) between February 2010 and December 2018 were studied. Microparticles of different dimensions according to two manufacturers (diameter of 70–150 μm, 100–300 μm or 300–500 μm and 40-μm, 75-μm or 100-μm) were used and loaded with 50–150 mg of doxorubicin. The objective tumour response according to the modified Response Evaluation Criteria in Solid Tumours (mRECIST), the time to progression, adverse events and overall survival were (OS) evaluated.</p></sec> <sec id="j_raon-2022-0019_s_007"><title style='display:none'>Results</title> <p>In total, 452 procedures were performed (median, 3 per patient). Four (0.9% of all procedures) major complications were noted. Postembolization syndrome occurred after 35% of procedures. At the first imaging follow-up 2–3 months after first treatment, 91% of patients achieved an objective response. The median time to progression was 10.2 months (95% CI: 8.3-12.1 months). OS rates at 1, 2, 3, 4, and 5 years were 85%, 53%, 33%, 20% and 14%, respectively. The median survival time was 25.8 months (95% CI: 22.1–29.5 months).</p></sec> <sec id="j_raon-2022-0019_s_008"><title style='display:none'>Conclusions</title> <p>DEM-TACE under CBCT control in patients with early and intermediate stage hepatocellular carcinoma is a safe and effective method of treatment with high objective tumour response and survival rates.</p></sec> </abstract>ARTICLE2022-05-08T00:00:00.000+00:00Treatment of skin tumors with intratumoral interleukin 12 gene electrotransfer in the head and neck region: a first-in-human clinical trial protocol<abstract> <title style='display:none'>Abstract</title> <sec id="j_raon-2022-0021_s_006"> <title style='display:none'>Background</title> <p>Immune therapies are currently under intensive investigation providing in many cases excellent responses in different tumors. Other possible approach for immunotherapy is a targeted intratumoral delivery of interleukin 12 (IL-12), a cytokine with anti-tumor effectiveness. Due to its immunomodulatory action, it can be used as an imunostimulating component to in situ vaccinating effect of local ablative therapies. We have developed a phIL12 plasmid devoid of antibiotic resistance marker with a transgene for human IL-12 p70 protein. The plasmid can be delivered intratumorally by gene electrotransfer (GET).</p> </sec> <sec id="j_raon-2022-0021_s_007"> <title style='display:none'>Patients and methods</title> <p>Here we present a first-in-human clinical trial protocol for phIL12 GET (ISRCTN15479959, ClinicalTrials NCT05077033). The study is aimed at evaluating the safety and tolerability of phIL12 GET in treatment of basal cell carcinomas in patients with operable tumors in the head and neck region. The study is designed as an exploratory, dose escalating study with the aim to determine the safety and tolerability of the treatment and to identify the dose of plasmid phIL12 that is safe and elicits its biological activity.</p> </sec> <sec id="j_raon-2022-0021_s_008"> <title style='display:none'>Conclusions</title> <p>The results of this trail protocol will therefore provide the basis for the use of phIL12 GET as an adjuvant treatment to local ablative therapies, to potentially increase their local and elicit a systemic response.</p> </sec> </abstract>ARTICLE2022-05-08T00:00:00.000+00:00Evaluation of toxic effects of chemotherapy in lung malignancies on cerebral white matter using diffusion tensor imaging<abstract> <title style='display:none'>Abstract</title> <sec id="j_raon-2022-0017_s_006"><title style='display:none'>Background</title> <p>Non-small cell lung cancer (NSCLC) is a leading cause of morbidity and mortality. Carboplatin and cisplatin based regimens are used in the treatment of NSCLC. The aim of the study was to find out whether there is a difference in white matter (WM) changes between two platinum-based chemotherapy agents using diffusion tensor imaging (DTI).</p></sec> <sec id="j_raon-2022-0017_s_007"><title style='display:none'>Patients and methods</title> <p>25 patients who received chemotherapy for NSCLC and 27 age-matched healthy controls were enrolled in the study. Fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD) and radial diffusivity (RD) values of the study population were measured from 11 regions of interest in pre-chemotherapy and post-chemotherapy MRI data.</p></sec> <sec id="j_raon-2022-0017_s_008"><title style='display:none'>Results</title> <p>Cisplatin group showed a significant decrease in the FA of the inferior longitudinal fasciculus (<italic>P</italic> = 0.028). Carboplatin group showed a significant FA decrease and RD increase in the forceps minor (<italic>P</italic> = 0.022 and <italic>P</italic> = 0.011, respectively), and a significant reduction in AD and increase in MD in frontal white matter (WM) (<italic>P</italic> = 0.008 and <italic>P</italic> = 0.029, respectively). In comparison of post chemotherapy DTI values of the two groups, carboplatin group showed lower FA, and higher MD and RD values than cisplatin group in parieto-occipital WM (<italic>P</italic> = 0.034, <italic>P</italic> = 0.034, <italic>P</italic> = 0.029, respectively).</p></sec> <sec id="j_raon-2022-0017_s_009"><title style='display:none'>Conclusions</title> <p>The findings of the study suggest that subtle effects of chemotherapy detectable with DTI may emerge after the treatment. In addition, carboplatin regimen may have more impact on WM than cisplatin regimen.</p></sec> </abstract>ARTICLE2022-05-04T00:00:00.000+00:00Advancements in the radiooncological treatment of high-risk prostate cancer: a quarter century of achievements<abstract> <title style='display:none'>Abstract</title> <sec id="j_raon-2022-0018_s_006"><title style='display:none'>Background</title> <p>The aim of the study was to evaluate the development of treatment of primary high-risk prostate cancer in regards to biochemical no evidence of disease (bNED), acute and late gastrointestinal (GI) and genitourinary (GU) side effects.</p></sec> <sec id="j_raon-2022-0018_s_007"><title style='display:none'>Patients and methods</title> <p>Primary high-risk prostate cancer patients treated between 1994 and 2016 were included. Applied doses ranged from 60 to 80 Gy, with a dose of 1.8 or 2 Gy per fraction. Techniques were either 3D conformal or intensity modulated radiotherapy and volumetric intensity modulated arc therapy.</p></sec> <sec id="j_raon-2022-0018_s_008"><title style='display:none'>Results</title> <p>142 patients were treated with doses up to 70 Gy (median dose 66 Gy; 66 Gy group), 282 with doses between 70 and 76 Gy (median dose 74 Gy; 74 Gy group), and 141 with doses &gt;76 Gy (median dose 78 Gy; 78 Gy group). The median follow-up was 48 months. The bNED rates were 50% after 5 years and 44% after 9 years in the 66 Gy group; 65% and 54%, respectively, in the 74 Gy group; and 83% and 66%, respectively, in the 78 Gy group (p = 0.03 <italic>vs</italic>. 74 Gy and p &lt; 0.0001 <italic>vs</italic>. 66 Gy). We found a higher rate of acute GI side effects in the 78 Gy group compared to the other groups, but not in maximum acute GU side effects and late maximum GI and GU effects.</p></sec> <sec id="j_raon-2022-0018_s_009"><title style='display:none'>Conclusions</title> <p>High-risk prostate cancer patients treated with doses of 78 Gy had significantly better bNED rates. Compared to the historical 66 Gy group, 50% more patients achieved bNED after a follow-up of 9 years.</p></sec> </abstract>ARTICLE2022-05-04T00:00:00.000+00:00Single centre experience with Excluder stent graft; 17-year outcome<abstract> <title style='display:none'>Abstract</title> <sec id="j_raon-2022-0008_s_006"> <title style='display:none'>Background</title> <p>Endovascular abdominal aortic aneurysm repair (EVAR) has become a mainstay of abdominal aorta aneurysm treatment. Long term follow-up on specific stent grafts is needed.</p></sec> <sec id="j_raon-2022-0008_s_007"> <title style='display:none'>Patients and methods</title> <p>This study included 123 patients (104 men; mean age 73.0 years, range 51–89) with abdominal aorta aneurysm, treated with Excluder<sup>®</sup> stent graft between October 2002 and June 2008. Periprocedural and follow-up data were retrieved by reviewing the records of our institution, while time and cause of death were retrieved from the National Institute of Public Health. If an abdominal aortic aneurysm rupture was listed as the cause of death, records were retrieved from the institution that issued the death certificate. Our primary goal was to assess the primary technical success rate, type 1 and type 2 endoleak, reintervention free survival, 30-day mortality, the overall survival and aneurysm rupture-free survival.</p></sec> <sec id="j_raon-2022-0008_s_008"> <title style='display:none'>Results</title> <p>The median follow-up was 9.7 years (interquartile range, 4.6–13.8). The primary technical success was 98.4% and the 30-day mortality accounted for 0.8%. Secondary procedures were performed in 29 (23.6%) patients during the follow-up period. The one-, five-, ten-, fifteen- and seventeen-year overall survival accounted for 94.3%, 74.0%, 47.2%, 35.8% and 35.8%, while the aneurysm-related survival was 98.4%, 96.3%, 92.6%, 92.6%, 92.6%. In seven (5.7%) patients, abdominal aortic rupture was found as the primary cause of death during follow-up.</p></sec> <sec id="j_raon-2022-0008_s_009"> <title style='display:none'>Conclusions</title> <p>Our data showed that EVAR with Excluder<sup>®</sup> stent graft offers good long-term results. More than 75% of patients can be treated completely percutaneously. Late ruptures do occur in the first ten years, raising awareness about regular medical controls.</p></sec></abstract>ARTICLE2022-04-13T00:00:00.000+00:00Image reconstruction using small-voxel size improves small lesion detection for positron emission tomography<abstract> <title style='display:none'>Abstract</title> <sec id="j_raon-2022-0015_s_006"> <title style='display:none'>Background</title> <p>PET/CT imaging is widely used in oncology and provides both metabolic and anatomic information. Because of the relatively poor spatial resolution of PET, the detection of small lesions is limited. The low spatial resolution introduces the partial-volume effect (PVE) which negatively affects images both qualitatively and quantitatively. The aim of the study was to investigate the effect of small-voxel (2 mm in-line pixel size) <italic><sub>vs.</sub></italic> standard-voxel (4 mm in-line pixel size) reconstruction on lesion detection and image quality in a range of activity ratios.</p></sec> <sec id="j_raon-2022-0015_s_007"> <title style='display:none'>Materials and methods</title> <p>The National Electrical Manufacturers Association (NEMA) body phantom and the Micro Hollow-Sphere phantom spheres were filled with a solution of [<sup>18</sup>F]fluorodeoxyglucose ([<sup>18</sup>F]FDG) in sphere-to-background ratios of 2:1, 3:1, 4:1 and 8:1. In all images reconstructed with 2 mm and 4 mm in-line pixel size the visual lesion delineation, contrast recovery coefficient (CRC) and contrast-to-noise ratio (CNR) were evaluated.</p></sec> <sec id="j_raon-2022-0015_s_008"> <title style='display:none'>Results</title> <p>For smaller (≤ 13 mm) phantom spheres, significantly higher CRC and CNR using small-voxel reconstructions were found, also improving visual lesion delineation. CRC did not differ significantly for larger (≥ 17 mm) spheres using 2 mm and 4 mm in-line pixel size, but CNR was significantly lower; however, lower CNR did not affect visual lesion delineation.</p></sec> <sec id="j_raon-2022-0015_s_009"> <title style='display:none'>Conclusions</title> <p>Small-voxel reconstruction consistently improves precise small lesion delineation, lesion contrast and image quality.</p></sec> </abstract>ARTICLE2022-04-13T00:00:00.000+00:00Various clinical presentations of uveitis associated with durvalumab treatment<abstract> <title style='display:none'>Abstract</title> <sec id="j_raon-2022-0007_s_005"><title style='display:none'>Background</title> <p>Immune checkpoint inhibitors (ICI) are becoming increasingly common in treating several cancer types. Durvalumab is a human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80 and has recently been approved for the treatment of extensive-stage small-cell lung cancer (ES-SCLC) and locally advanced unresectable (NSCLC). The present review aimed to analyse immune-mediated uveitis, secondary to durvalumab treatment, through a review of the literature and a presentation of two clinical cases.</p></sec> <sec id="j_raon-2022-0007_s_006"><title style='display:none'>Patients and methods</title> <p>A literature review using PubMed search was conducted to identify cases of uveitis secondary to durvalumab and cases of uveitis with optic disc oedema secondary to ICI use that were reported prior to November 14, 2021. Additionally, we report two cases of uveitis consequent on durvalumab treatment.</p></sec> <sec id="j_raon-2022-0007_s_007"><title style='display:none'>Results</title> <p>Five cases of uveitis secondary to durvalumab use were identified in the literature. Anterior, posterior uveitis and vasculitis were reported. Additionally, we present a case of bilateral intermediate uveitis with bilateral optic disc oedema and a case of bilateral posterior uveitis. Our further search revealed 12 cases of uveitis with optic disc oedema secondary to ICI use, with the majority of cases reported secondary to PD-1 inhibitors.</p></sec> <sec id="j_raon-2022-0007_s_008"><title style='display:none'>Conclusions</title> <p>Rarely reported, uveitis secondary to durvalumab can present various clinical pictures and requires a thorough diagnostic workup. Once the diagnosis is established, treatment, commonly with a local or systemic corticosteroid, should be adapted to the severity of the inflammation.</p></sec> </abstract>ARTICLE2022-04-12T00:00:00.000+00:00Co-treatment with vactosertib, a novel, orally bioavailable activin receptor-like kinase 5 inhibitor, suppresses radiotherapy-induced epithelial-to-mesenchymal transition, cancer cell stemness, and lung metastasis of breast cancer<abstract> <title style='display:none'>Abstract</title> <sec id="j_raon-2022-0012_s_005"> <title style='display:none'>Background</title> <p>Acquired metastasis and invasion of cancer cells during radiotherapy are in part due to induction of epithelial-to-mesenchymal transition (EMT) and cancer stem cell (CSC) properties, which are mediated by TGF-β signaling. Here we evaluated the anti-metastatic therapeutic potential of vactosertib, an orally bioavailable TGF-β type I receptor (activin receptor-like kinase 5, ALK5) inhibitor, via suppression of radiation-induced EMT and CSC properties, oxidative stress generation, and breast to lung metastasis in a breast cancer mouse model and breast cancer cell lines.</p> </sec> <sec id="j_raon-2022-0012_s_006"> <title style='display:none'>Materials and methods</title> <p>Co-treatment of vactosertib with radiation was investigated in the 4T1-Luc allografted BALB/c syngeneic mouse model and in 4T1-Luc and MDA-MB-231 cells. The anti-metastatic therapeutic potential of vactosertib in breast cancer was investigated using fluorescence immunohistochemistry, real-time quantitative reverse transcription-polymerase chain reaction, western blotting, wound healing assay, mammosphere formation assay, and lung metastasis analysis <italic>in vitro</italic> and <italic>in vivo</italic>.</p> </sec> <sec id="j_raon-2022-0012_s_007"> <title style='display:none'>Results</title> <p>Radiation induced TGF-β signaling, EMT markers (Vimentin, Fibronectin, Snail, Slug, Twist, and N-cadherin), CSC properties (expression of pluripotent stem cell regulators, mammosphere forming ability), reactive oxygen species markers (NOX4, 4-HNE), and motility of breast cancer cells <italic>in vitro</italic> and <italic>in vivo</italic>. Vactosertib attenuated the radiation-induced EMT and CSC properties by inhibiting ROS stress in breast cancer. Moreover, vactosertib combined with radiation showed a significant anti-metastatic effect with suppression of breast to lung metastasis <italic>in vivo</italic>.</p> </sec> <sec id="j_raon-2022-0012_s_008"> <title style='display:none'>Conclusions</title> <p>These results indicate that inhibition of TGF-β signaling with vactosertib in breast cancer patients undergoing radiotherapy would be an attractive strategy for the prevention of cancer metastasis and recurrence.</p> </sec> </abstract>ARTICLE2022-04-07T00:00:00.000+00:00Expression of DNA-damage response and repair genes after exposure to DNA-damaging agents in isogenic head and neck cells with altered radiosensitivity<abstract> <title style='display:none'>Abstract</title> <sec id="j_raon-2022-0014_s_005"> <title style='display:none'>Background</title> <p>Increased radioresistance due to previous irradiation or radiosensitivity due to human papilloma virus (HPV) infection can be observed in head and neck squamous cell carcinoma (HNSCC). The DNA-damage response of cells after exposure to DNA-damaging agents plays a crucial role in determining the fate of exposed cells. Tightly regulated and interconnected signaling networks are activated to detect, signal the presence of and repair the DNA damage. Novel therapies targeting the DNA-damage response are emerging; however, an improved understanding of the complex signaling networks involved in tumor radioresistance and radiosensitivity is needed.</p> </sec> <sec id="j_raon-2022-0014_s_006"> <title style='display:none'>Materials and methods</title> <p>In this study, we exposed isogenic human HNSCC cell lines with altered radiosensitivity to DNA-damaging agents: radiation, cisplatin and bleomycin. We investigated transcriptional alterations in the DNA-damage response by using a pathway-focused panel and reverse-transcription quantitative PCR.</p></sec> <sec id="j_raon-2022-0014_s_007"> <title style='display:none'>Results</title> <p>In general, the isogenic cell lines with altered radiosensitivity significantly differed from one another in the expression of genes involved in the DNA-damage response. The radiosensitive (HPV-positive) cells showed overall decreases in the expression levels of the studied genes. In parental cells, upregulation of DNA-damage signaling and repair genes was observed following exposure to DNA-damaging agents, especially radiation. In contrast, radioresistant cells exhibited a distinct pattern of gene downregulation after exposure to cisplatin, whereas the levels in parental cells were unchanged. Exposure of radioresistant cells to bleomycin did not significantly affect the expression of DNA-damage signaling and repair genes.</p></sec> <sec id="j_raon-2022-0014_s_008"> <title style='display:none'>Conclusions</title> <p>Our analysis identified several possible targets: NBN, XRCC3, ATR, GADD45A and XPA. These putative targets should be studied and potentially exploited for sensibilization to ionizing radiation and/or cisplatin in HNSCC. The use of predesigned panels of DNA-damage signaling and repair genes proved to offer a convenient and quick approach to identify possible therapeutic targets.</p> </sec> </abstract>ARTICLE2022-04-07T00:00:00.000+00:00Moderate hypofractionated helical tomotherapy for older patients with localized prostate cancer: long-term outcomes of a phase I–II trial<abstract> <title style='display:none'>Abstract</title> <sec id="j_raon-2022-0011_s_005"> <title style='display:none'>Background</title> <p>Our previous study showed that two different regimens of moderate hypofractionated radiotherapy (HFRT) delivered with helical tomotherapy (HT) are well tolerated in older prostate cancer patients. We provide a longterm efficacy and toxicity after &gt; 7 years of follow-up.</p></sec> <sec id="j_raon-2022-0011_s_006"> <title style='display:none'>Patients and methods</title> <p>The study recruited 33 patients from February 2009 to July 2011 (76 Gy/34F; Group-1); and 34 from July 2011 to February 2014 (71.6 Gy/28F; 50.4 Gy/25F for the risk of pelvic lymph nodes involvement (LNI) &gt;15%; Group-2). The primary outcomes were biochemical failure (BF), biochemical failure and clinical disease failure (BCDF), progression-free survival (PFS), overall survival (OS), late genitourinary (GU) and gastrointestinal (GI) toxicity.</p></sec> <sec id="j_raon-2022-0011_s_007"> <title style='display:none'>Results</title> <p>The average ages of two groups were 80 and 77 years and the proportions of patients with LNI &gt; 15% were 69.7% and 73.5%, respectively. At the final follow-up in February 2020, 27.3% and 20.6% cases experienced BF, with a median time until BF of 3.3 years. A total of 38.8% patients reached primary endpoints, in which 18 deaths were reported BCDF events (45.5% <italic>vs</italic>. 32.4%, p = 0.271). There was no significant difference in 7-year PFS (68.6% <italic>vs</italic>. 74.8%, p = 0.591), BCDF (45.5% <italic>vs</italic>. 32.4%, p = 0.271) and OS (71.9% <italic>vs</italic>. 87.5%, p = 0.376) for full set analysis and for subgroup analysis (all p &gt; 0.05). The incidence of grade ≥ 2 late GU (6.2% <italic>vs</italic>. 6.3%, p = 0.127) and GI toxicities (9.4% <italic>vs</italic>. 15.6%, p = 0.554) was comparable.</p></sec> <sec id="j_raon-2022-0011_s_008"> <title style='display:none'>Conclusions</title> <p>In older patients with localized prostate cancer, two moderate hypofractionated regimens were all well tolerated with similar, mild late toxicities and satisfactory survival, without necessity of prophylactic pelvic node irradiation.</p></sec> </abstract>ARTICLE2022-03-28T00:00:00.000+00:00Radiomic features as biomarkers of soft tissue paediatric sarcomas: preliminary results of a PET/MR study<abstract> <title style='display:none'>Abstract</title> <sec id="j_raon-2022-0013_s_005"> <title style='display:none'>Background</title> <p>Pediatric soft tissue sarcomas are rare tumors with rhabdomyosarcoma being the most frequent histotype. Diagnostic imaging plays a significant role in the evaluation of this type of tumors. Thus, aim of this study was to assess the prognostic and diagnostic value of radiomic features extracted from axial T2w images of the primary lesion in children with soft tissue sarcomas examined by PET/MR for staging.</p> </sec> <sec id="j_raon-2022-0013_s_006"> <title style='display:none'>Methods</title> <p>Using an open source software, each lesion was segmented and 33 radiomic features then extracted. Factor and logistic regression analyses were applied to select highly correlating features and evaluate their prognostic role, respectively. Differences in radiomic, demographics, metabolic, and laboratory variables according to tumor grade and histotype were investigated by the Students’ and Chi-square tests. In case of differences the diagnostic value of the variable/s was assessed by receiver operating curves.</p></sec> <sec id="j_raon-2022-0013_s_007"> <title style='display:none'>Results</title> <p>Eighteen children (11 female; mean age 7.8 ± 4.6-year-old) matched the inclusion criteria. The factor analysis allowed the selection of five highly correlating features which, according to regression analysis, did not influence the outcome (p &gt; 0.05, each). The feature lmc1 was significantly higher in low grade lesions (p = 0.045) and showed 70.4% accuracy in classifying high grade tumors while the feature variance was significantly lower in rhabdomyosarcomas (p = 0.008) and showed 83.3% accuracy for this histotype.</p></sec> <sec id="j_raon-2022-0013_s_008"> <title style='display:none'>Conclusions</title> <p>In conclusion, our preliminary results suggest that specific radiomic features may act as biomarkers of pediatric soft tissue sarcoma grade and histotype.</p> </sec> </abstract>ARTICLE2022-03-28T00:00:00.000+00:00Sunitinib potentiates the cytotoxic effect of electrochemotherapy in pancreatic carcinoma cells<abstract> <title style='display:none'>Abstract</title> <sec id="j_raon-2022-0009_s_005"> <title style='display:none'>Background</title> <p>One of the new treatment options for unresectable locally advanced pancreatic cancer is electrochemotherapy (ECT), a local ablative therapy that potentiates the entry of chemotherapeutic drugs into the cells, by the application of an electric field to the tumor. Its feasibility and safety were demonstrated in preclinical and clinical studies; however, there is a lack of preclinical studies assessing the actions of different drugs used in ECT, their mechanisms and interactions with other target drugs that are used in clinical practice.</p> </sec> <sec id="j_raon-2022-0009_s_006"> <title style='display:none'>Materials and methods</title> <p>The aim of the study was to determine the cytotoxicity of two chemotherapeutic drugs usually used in ECT (bleomycin and cisplatin) in the BxPC-3 human pancreatic carcinoma cell line and evaluate the interactions of ECT with the targeted drug sunitinib. First, the cytotoxicity of ECT using both chemotherapeutics was determined. In the next part, the interactions of ECT and sunitinib were evaluated through determination of combined cytotoxicity, sunitinib targets and kinetics of cell death.</p> </sec> <sec id="j_raon-2022-0009_s_007"> <title style='display:none'>Results</title> <p>The results demonstrate that ECT is effective in pancreatic cancer cell line, especially when bleomycin is used, with the onset of cell death in the first hours after the treatment, reaching a plateau at 20 hours after the treatment. Furthermore, we provide the rationale for combining ECT with bleomycin and the targeted drug sunitinib to potentiate cytotoxicity. The combined treatment of sunitinib and ECT was synergistic for bleomycin only at the highest used concentration of bleomycin 0.14 μM, whereas with lower doses of bleomycin, this effect was not observed. The interaction of ECT and treatment with sunitinib was confirmed by course of the cell death, also indicating on synergism.</p></sec> <sec id="j_raon-2022-0009_s_008"> <title style='display:none'>Conclusions</title> <p>ECT and sunitinib combined treatment has clinical potential, and further studies are warranted.</p></sec></abstract>ARTICLE2022-03-28T00:00:00.000+00:00Does CyberKnife improve dose distribution versus IMRT and VMAT on a linear accelerator in low-risk prostate cancer?<abstract> <title style='display:none'>Abstract</title> <sec id="j_raon-2022-0010_s_006"> <title style='display:none'>Background</title> <p>Hypofractionated stereotactic body radiation therapy (SBRT) for prostate cancer (PCa) can be delivered with the robot-assisted CyberKnife (CK) system or on a linear accelerator using dynamic intensity-modulated radiotherapy (IMRT) or volumetric arc radiotherapy (VMAT). This retrospective study was performed to determine whether CK offers better dose distribution than IMRT and/or VMAT.</p> </sec> <sec id="j_raon-2022-0010_s_007"> <title style='display:none'>Materials and methods</title> <p>Treatment plans for three techniques were prepared using the same treatment parameters (36.35 Gy, 7.25 Gy/fr). We evaluated target coverage, conformity index (CI), homogeneity index (HI), gamma index (GI), and organs at risk (OAR) constraints.</p></sec> <sec id="j_raon-2022-0010_s_008"> <title style='display:none'>Results</title> <p>The mean planning target volume (PTV) dose for CK (39.58 Gy) was significantly greater than VMAT or IMRT (both 36.25 Gy). However, CK resulted in a wider dose range (31.48 to 45.89 Gy) <italic>vs</italic>. VMAT and IMRT (34.6–38.76 Gy). The mean dose to the rectum (V36Gy, mm<sup>3</sup>) was significantly lower (p &lt; 0.001) in the CK plans (219.78 <italic>vs</italic>. 519.59 and 422.62, respectively). The mean bladder dose (V37Gy, mm<sup>3</sup>) was significantly greater for CK (3256 <italic>vs</italic>. 1090.75 for VMAT and 4.5 for IMRT (p &lt; 0.001). CK yielded significantly better CI (1.07 <italic>vs</italic>. 1.17 and 1.25 for VMAT and IMRT, respectively; p &lt; 0.01) and HI values (1.27 <italic>vs</italic>. 1.07 and 1.04; p &lt; 0.01). GI values for the δd = 3mm, δ% = 3% criteria were 99.86 (VMAT), 99.07 (IMRT) and 99.99 (CK). For δd = 2mm, δ% = 2%, the corresponding values were 98.3, 93.35, and 97.12, respectively.</p></sec> <sec id="j_raon-2022-0010_s_009"> <title style='display:none'>Conclusions</title> <p>For most variables, CK was superior to both VMAT and IMRT. However, dynamic IMRT techniques, especially VMAT, do not differ significantly from CK plans and are therefore acceptable alternatives to CyberKnife.</p> </sec> </abstract>ARTICLE2022-03-28T00:00:00.000+00:00Clinical impact of post-progression survival in patients with locally advanced non-small cell lung cancer after chemoradiotherapy<abstract> <title style='display:none'>Abstract</title> <sec id="j_raon-2022-0006_s_006"> <title style='display:none'>Background</title> <p>The efficacy of first-line chemoradiotherapy for overall survival (OS) might be confounded by the subsequent treatments in patients with locally advanced non-small cell lung cancer (NSCLC). In this study, we assessed the associations of progression-free survival (PFS) and post-progression survival (PPS) with OS after chemoradiotherapy for locally advanced NSCLC using patient-level data.</p> </sec> <sec id="j_raon-2022-0006_s_007"> <title style='display:none'>Patients and methods</title> <p>Between January 2011 and December 2018, 45 patients with locally advanced NSCLC who had received first-line chemoradiotherapy and in whom recurrence occurred were analysed. The associations of PFS and PPS with OS were analysed at the individual level.</p></sec> <sec id="j_raon-2022-0006_s_008"> <title style='display:none'>Results</title> <p>Linear regression and Spearman rank correlation analyses revealed that PPS was strongly correlated with OS (<italic>r</italic> = 0.72, <italic>p</italic> &lt; 0.05, <italic>R</italic>2 = 0.54), whereas PFS was moderately correlated with OS (<italic>r</italic> = 0.58, <italic>p</italic> &lt; 0.05, <italic>R</italic><sup><xref ref-type="bibr" rid="j_raon-2022-0006_ref_002">2</xref></sup> = 0.34). The Glasgow prognostic score and liver metastases at recurrence were significantly associated with PPS (<italic>p</italic> &lt; 0.001).</p></sec> <sec id="j_raon-2022-0006_s_009"> <title style='display:none'>Conclusions</title> <p>The current analysis of individual-level data of patients treated with first-line chemoradiotherapy implied that PPS had a higher impact on OS than PFS in patients with locally advanced NSCLC. Additionally, current perceptions indicate that treatment beyond progression after first-line chemoradiotherapy might strongly affect OS.</p> </sec> </abstract>ARTICLE2022-02-25T00:00:00.000+00:00Assessment of hyperbaric oxygenation treatment response in parotid glands by mapping following radiotherapy for head and neck tumours<abstract><title style='display:none'>Abstract</title> <sec id="j_raon-2022-0001_s_006"> <title style='display:none'>Background</title> <p>The study was designed to evaluate the influence of hyperbaric oxygenation therapy (HBOT) on the parotid gland in patients following radiotherapy for head and neck tumours.</p></sec> <sec id="j_raon-2022-0001_s_007"> <title style='display:none'>Patients and methods</title> <p>HBOT response was monitored by 3T magnetic resonance imaging (MRI) using <italic>T</italic><sub>2</sub> mapping and subsequent measurement of mean <italic>T</italic><sub>2</sub> and <italic>T</italic><sub>2</sub> variability as well as by salivary tests (salivary flow, buffer capacity, and pH). Eighteen patients previously treated with irradiation doses between 50 and 80 Gy as well as 18 healthy gender and age matched controls were enrolled. MRI was performed prior to HBOT (40.2 ± 20 months after radiotherapy) and after 20 daily HBOT at 2.5 ATA (absolute atmosphere). Each HBOT consisted of breathing 100% oxygen for 90 minutes.</p></sec> <sec id="j_raon-2022-0001_s_008"> <title style='display:none'>Results</title> <p>Significant differences in mean <italic>T</italic><sub>2</sub> prior to HBOT were observed between the ipsilateral irradiated (121 ± 20 ms), contralateral parotids (107 ± 21) and control group (96 ± 12 ms). A positive correlation in patients between <italic>T</italic><sub>2</sub> variability and irradiation dose was detected in contralateral parotids before HBOT (R = 0.489, p = 0.0287). In addition, negative correlations were observed between mean <italic>T</italic><sub>2</sub> in the ipsilateral as well as the contralateral gland and salivary flow before and after HBOT. Negative correlations between mean <italic>T</italic><sub>2</sub>, <italic>T</italic><sub>2</sub> variability and pH of unstimulated saliva were also observed in the sides of parotid before and after HBOT.</p></sec> <sec id="j_raon-2022-0001_s_009"> <title style='display:none'>Conclusions</title> <p>The study confirmed that <italic>T</italic><sub>2</sub> mapping had a potential for monitoring the differences between irradiated and normal parotid glands. It could also be useful in the assessment of the glandular tissue response to HBOT.</p></sec></abstract>ARTICLE2022-02-11T00:00:00.000+00:00Efficacy of transvaginal ultrasound versus magnetic resonance imaging for preoperative assessment of myometrial invasion in patients with endometrioid endometrial cancer: a prospective comparative study<abstract><title style='display:none'>Abstract</title> <sec id="j_raon-2022-0005_s_007"> <title style='display:none'>Background</title> <p>We compared the accuracy of preoperative transvaginal ultrasound (TVUS) <italic>versus</italic> magnetic resonance imaging (MRI) for the assessment of myometrial invasion (MI) in patients with endometrial cancer (EC), while definitive histopathological diagnosis served as a reference method.</p></sec> <sec id="j_raon-2022-0005_s_008"> <title style='display:none'>Patients and methods</title> <p>Study performed at a single tertiary centre from 2019 to 2021, included women with a histopathological proven EC, hospitalized for scheduled surgery. TVUS and MRI were performed prior to surgical staging for assessment MI, which was estimated using two objective TVUS methods (Gordon’s and Karlsson’s) and MRI. Patients were divided into two groups, after surgery and histopathological assessment of MI: superficial (≤ 50%) and deep (&gt; 50%).</p></sec> <sec id="j_raon-2022-0005_s_009"> <title style='display:none'>Results</title> <p>Sixty patients were eligible for the study. According to the reference method, there were 34 (56.7%) cases in the study with MI &lt; 50%, and 26 (43.3%) with MI &gt; 50%. Both objective TVUS methods and MRI showed no statistical significant differences in overall diagnostic performance for the preoperative assessment of MI. The concordance coefficient between both TVUS methods, MRI and histopathology was statistically significant (p &lt; 0.001). Gordon’s method calculating MI reached a positive predictive value (PPV) of 83%, negative predictive value (NPV) of 83%, 77% sensitivity, 88% specificity, and 83% overall accuracy. Karlsson’s method reached PPV of 82%, NPV of 79%, 69% sensitivity, 88% specificity, and 80% overall accuracy. Accordingly, MRI calculating MI reached PPV of 83%, NPV of 97%, 97% sensitivity, 85% specificity, and 90% overall accuracy.</p></sec> <sec id="j_raon-2022-0005_s_010"> <title style='display:none'>Conclusions</title> <p>We found that objective TVUS assessment of myometrial invasion was performed with a diagnostic accuracy comparable to that of MRI in women with endometrial cancer.</p></sec></abstract>ARTICLE2022-02-11T00:00:00.000+00:00Cancer gene therapy goes viral: viral vector platforms come of age<abstract> <title style='display:none'>Abstract</title> <sec id="j_raon-2022-0002_s_007"> <title style='display:none'>Background</title> <p>Since the advent of viral vector gene therapy in 1990s, cancer treatment with viral vectors promised to revolutionize the field of oncology. Notably, viral vectors offer a unique combination of efficient gene delivery and engagement of the immune system for anti-tumour response. Despite the early potential, viral vector-based cancer treatments are only recently making a big impact, most prominently as gene delivery devices in approved CAR-T cell therapies, cancer vaccines and targeted oncolytic therapeutics. To reach this broad spectrum of applications, a number of challenges have been overcome – from our understanding of cancer biology to vector design, manufacture and engineering. Here, we take an overview of viral vector usage in cancer therapy and discuss the latest advancements. We also consider production platforms that enable mainstream adoption of viral vectors for cancer gene therapy.</p></sec> <sec id="j_raon-2022-0002_s_008"> <title style='display:none'>Conclusions</title> <p>Viral vectors offer numerous opportunities in cancer therapy. Recent advances in vector production platforms open new avenues in safe and efficient viral therapeutic strategies, streamlining the transition from lab bench to bedside. As viral vectors come of age, they could become a standard tool in the cancer treatment arsenal.</p></sec></abstract>ARTICLE2022-02-11T00:00:00.000+00:00Percutaneous electrochemotherapy in primary and secondary liver malignancies – local tumor control and impact on overall survival<abstract><title style='display:none'>Abstract</title> <sec id="j_raon-2022-0003_s_005"> <title style='display:none'>Background</title> <p>Local nonsurgical tumor ablation currently represents a further option for the treatment of patients with liver tumors or metastases. Electrochemotherapy (ECT) is a welcome addition to the portfolio of local therapies. A retrospective analysis of patients with liver tumors or metastases treated with ECT is reported. Attention is given to the safety and efficacy of the treatment over time.</p></sec> <sec id="j_raon-2022-0003_s_006"> <title style='display:none'>Patients and methods</title> <p>Eighteen consecutive patients were recruited with measurable liver tumors of different histopatologic origins, mainly colorectal cancer, breast cancer, and hepatocellular cancer. They were treated with percutaneous ECT following the standard operating procedures (SOP) for ECT under general anaesthesia and muscle relaxation. Treatment planning was performed based on MRI preoperative images. The follow-up assessment included contrast-enhanced MR within at least 1–3 months after treatment and then after 5, 7, 9, 12, and 18 months until progression of the disease or death.</p></sec> <sec id="j_raon-2022-0003_s_007"> <title style='display:none'>Results</title> <p>Only mild or moderate side effects were observed after ECT. The objective response rate was 85.7% (complete response 61.9%, partial 23.8%), the mean progression-free survival (PFS) was 9.0 ± 8.2 months, and the overall survival (OS) was 11.3 ± 8.6 months. ECT performed best (PFS and OS) in lesions within 3 and 6 cm diameters (p = 0.0242, p = 0.0297)<bold><sub>.</sub></bold> The effectiveness of ECT was independent of the localization of the lesions: distant, close or adjacent to vital structures. Progression-free survival and overall survival were independent of the primary histology considered.</p></sec> <sec id="j_raon-2022-0003_s_008"> <title style='display:none'>Conclusions</title> <p>Electrochemotherapy provides an effective valuable option for the treatment of unresectable liver metastases not amenable to other ablative techniques.</p></sec></abstract>ARTICLE2022-02-11T00:00:00.000+00:00en-us-1