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Malignant tumors are a leading cause of death worldwide, second only to cardiovascular disease. They occur in every population and have a high risk of mortality. The etiopathogenesis of malignant tumors is diverse and there are still many unknowns, leading to huge diagnostic and therapeutic challenges. Therefore, the search for ideal diagnostic and therapeutic agents is ongoing. One of the promising factors affecting cancer is the nucleus accumbens associated protein 1 (NACC1). It is a transcriptional coregulator. Moreover, it plays a multifaceted role in promoting tumorigenesis. NACC1 expression analyses were performed using The Cancer Genome Atlas (TCGA) data accessed from the University of Alabama at Birmingham Cancer (UALCAN) database, and the expression data were interconnected with clinicopathological parameters. All statistical analyses were conducted using GraphPad Prism and Statistica. The results revealed that NACC1 was expressed in almost all of the analyzed cancers, and its expression level correlates with different clinicopathological parameters. This study demonstrates that NACC1 is potentially involved in the pathogenesis, invasion, and immune response associated with many cancers. However, NACC1 is not a suitable candidate as a diagnostic biomarker as it is not specific for any type of malignancy and there are discrepancies in its expression in relation to many clinicopathological parameters. The implementation of NACC1 as a therapeutic target may improve the effectiveness of cancer treatments.

Background: The biological effects and clinical consequences of out-of-field radiation in peripheral organs can be difficult to determine, especially for low doses (0.1 Gy-1 Gy). In recent years, Monte Carlo (MC) methods have been proposed to more accurately predict nontarget doses. The aim of the present study was to assess the feasibility of using Monte Carlo methods to predict the biological response of tissues and critical organs to low dose radiation (0.1 to 1 Gy) based on results published in the literature., Materials and Methods: Literature review, including studies published by our group., Results and Conclusions: It has long been assumed that radiation doses to peripheral organs located far from the target volume are too low to have any clinical impact. In recent years, however, concerns about the risk of treatment-induced secondary cancers, even in peripheral organs, have continued to grow in line with increasing life expectancy. At present, it is difficult in routine calculations to accurately determine radiation doses to the whole body and peripheral organs. Moreover, the potential clinical impact of these doses remains uncertain and the biological response to low dose radiation depends on the organ. In this context, MC methods can predict biological response in those organs. Monte Carlo methods have become a powerful tool to better predict the consequences of interactions between ionising radiation and biological matter. MC modelling can also help to characterise microscopic system dynamics and to provide a better understanding of processes occurring at the cellular, molecular, and nanoscales., Competing Interests: Conflict of interests: Authors declare no conflict of interests., (© 2024 Greater Poland Cancer Centre.)

Research on different types of ionizing radiation's effects has been ongoing for years, revealing its efficacy in damaging cancer cells. Solid tumors comprise diverse cell types, each being able to respond differently to radiation. This study evaluated the radiobiological response of established (MDA-MB-231 (Triple negative breast cancer, TNBC), MCF-7 (Luminal A)) and patient-derived malignant cell lines, cancer-associated fibroblasts, and skin fibroblasts following proton IRR. All cell line types were irradiated with the proton dose of 2, 4, and 6 Gy. The radiobiological response was assessed using clonogenic assay, γH2AX, and p53 staining. It was noticeable that breast cancer lines of different molecular subtypes displayed no significant variations in their response to proton IRR. In terms of cancer-associated fibroblasts extracted from the tumor tissue, the line derived from a TNBC subtype tumor demonstrated higher resistance to ionizing radiation compared to lines isolated from luminal A tumors. Fibroblasts extracted from patients' skin responded identically to all doses of proton radiation. This study emphasizes that tumor response is not exclusively determined by the elimination of breast cancer cells, but also takes into account tumor microenvironmental variables and skin reactions.

This case report discusses a rare pediatric case of granulomatosis with polyangiitis (GPA) presenting with hemoptysis, migratory polyarthralgia, significant laboratory abnormalities, and imaging findings. GPA is a form of vasculitis that primarily affects the upper and lower respiratory tracts and the kidneys. Pediatric cases, though rare, offer a distinct set of clinical challenges. The patient presented to the emergency department with hemoptysis, joint pain, and cough. Radiologic findings included diffuse bilateral nodular airspace opacities on chest X-ray (CXR) and ground glass opacities on computed tomography (CT). After hospital admission, the patient's bronchoscopy suggested diffuse alveolar hemorrhage. Laboratory tests were positive for proteinase 3 (PR3), indicating a possible diagnosis of GPA. Further tests, consultations, and evaluations corroborated this diagnosis. Treatment administered included high-dose intravenous steroids, rituximab, and other supportive measures. Pediatric GPA, while rare, is a challenging diagnostic entity. A comprehensive and multidisciplinary approach is pivotal for timely diagnosis and initiation of appropriate therapy., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Anderson et al.)

Gastric cancer (GC) is one of the most frequently diagnosed cancers in the world. Although the incidence is decreasing in developed countries, the treatment results are still unsatisfactory. The standard treatment for locally advanced gastric cancer (LAGC) is gastrectomy with perioperative chemotherapy. The association of selected microRNAs (miRNAs) with chemoresistance was assessed using archival material of patients with LAGC. Histological material was obtained from each patient via a biopsy performed during gastroscopy and then after surgery, which was preceded by four cycles of neoadjuvant chemotherapy (NAC) according to the FLOT or FLO regimen. The expression of selected miRNAs in the tissue material was assessed, including miRNA-21-3p , miRNA-21-5p , miRNA-106a-5p , miRNA-122-3p , miRNA-122-5p , miRNA-143-3p , miRNA-143-5p , miRNA-203a-3p , miRNA-203-5p , miRNA-551b-3p , miRNA-551b-5p , and miRNA-574-3p . miRNA expression was assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The response to NAC was assessed using computed tomography of the abdomen and chest and histopathology after gastrectomy. The statistical analyses were performed using GraphPad Prism 9. The significance limit was set at p < 0.05. We showed that the expression of miR-143-3p , miR-143-5p , and miR-574-3p before surgery, and miR-143-5p and miR-574-3p after surgery, decreased in patients with GC. The expression of miR-143-3p , miR-143-5p , miR-203a-3p , and miR-551b-5p decreased in several patients who responded to NAC. The miRNA most commonly expressed in these cases was miRNA-551b-5p . Moreover, it showed expression in a patient whose response to chemotherapy was inconsistent between the histopathological results and computed tomography. The expression of miR-143-3p , miR-143-5p , miR-203a-3p , and miR-551b-5p in formalin-fixed paraffin-embedded tissue (FFPET) samples can help differentiate between the responders and non-responders to NAC in LAGC. miR-143-3p , miR-143-5p , and miR-574-3p expression may be used as a potential diagnostic tool in GC patients. The presence of miR-551b-5p may support the correct assessment of a response to NAC in GC via CT.

Background/objectives: Surgical populations and particularly injury survivors often present with complex trauma that elevates their risk for prolonged opioid use and misuse. Changes in opioid prescribing guidelines during the past several years have yielded mixed results for pain management after trauma, with a limiting factor being the heterogeneity of clinical populations and treatment needs in individuals receiving opioids. The present analysis illuminates this gap between clinical guidelines and clinical practice through qualitative feedback from hospital trauma providers and unit staff members regarding current opioid prescribing guidelines and practices in the setting of traumatic injury., Methods: The parent study aimed to implement a pilot screening tool for opioid misuse in four level I and II trauma hospitals throughout Wisconsin. As part of the parent study, focus groups were conducted at each study site to explore the facilitators and barriers of implementing a novel screening tool, as well as to examine the current opioid prescribing guidelines, trainings, and resources available for trauma and acute care providers. Focus group transcripts were independently coded and analyzed using a modified grounded theory approach to identify themes related to the facilitators and barriers of opioid prescribing guidelines in trauma and acute care., Results: Three major themes were identified as impactful to opioid-related prescribing and care provided in the setting of traumatic injury; these include (1) acute treatment strategies; (2) patient interactions surrounding pain management; and (3) the multifactorial nature of trauma on pain management approaches., Conclusion: Providers and staff at four Wisconsin trauma centers called for trauma-specific opioid prescribing guidelines in the setting of trauma and acute care. The ubiquitous prescription of opioids and challenges in long-term pain management in these settings necessitate additional community-integrated research to inform development of federal guidelines., Level of Evidence: Therapeutic/care management, level V., Competing Interests: Competing interests: The authors alone are responsible for the content and writing of this paper. TSACO Disclosure forms have been supplied for each author and are available upon request., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Primary cell lines are invaluable for exploring cancer biology and investigating novel treatments. Despite their numerous advantages, primary cultures are laborious to obtain and maintain in culture. Hence, established cell lines are still more common. This study aimed to evaluate a range of techniques for isolating primary breast cancer cultures, employing distinct enzymatic compositions, incubation durations, and mechanical approaches, including filtration. Out of several protocols, we opted for a highly effective method (Method 5) that gave rise to a primary cell culture (BC160). This method combines mechanical disaggregation and enzymatic digestion with hyaluronidase and collagenase. Moreover, the paper addresses common issues in isolating primary cultures, shedding light on the struggle against fibroblasts overgrowing cancer cell populations. To make primary cell lines a preferred model, it is essential to elaborate and categorise isolation methods, develop approaches to separate heterogeneous cultures and investigate factors influencing the establishment of primary cell lines., (© 2023. The Author(s).)

Background: As opioid overdoses continue rising, interventions are needed to expand naloxone carriage, an opioid overdose reversal agent. Use of fentanyl test strips (FTS) might promote naloxone carriage. This study examines the relationship between FTS use, perceived overdose risk, and naloxone carriage in Wisconsin, United States. Methods: In a survey of people who use drugs ( n  = 341) in southern Wisconsin, respondents were asked about FTS use, perceived overdose risk, and how often they (1) have naloxone, (2) have more than one dose of naloxone, and (3) the number of naloxone doses possessed currently. Likert responses were mapped to an integer scale. Ordinal and linear multivariable regression examined the relationship between FTS use and study outcomes while adjusting for respondent characteristics. Results: Most respondents were male (59.6%), identified heroin as their drug of choice (70.7%) and reported intravenous use (87.9%). In unadjusted models, FTS use was associated with more often having naloxone (OR: 2.10; p  = 0.005), more often having multiple naloxone doses (OR: 2.98; p  < 0.001), and possessing a greater number of naloxone doses (dose count difference: 2.85; p  = 0.001). In adjusted models, FTS use was associated with more often having multiple naloxone doses (OR: 2.29; p  = 0.005) and possessing a greater number of naloxone doses (dose count difference: 2.25, p  = 0.020). Conclusions: Individuals who use FTS more often carry multiple doses relative to individuals who do not use FTS. Given that naloxone carriage is critical for reducing opioid overdose risk, expanding FTS use may offer a strategy to reduce opioid overdose rates via improved naloxone carriage.

Background: Clinical audits are an important tool to objectively assess clinical protocols, procedures, and processes and to detect deviations from good clinical practice. The main aim of this project is to determine adherence to a core set of consensus- based quality indicators and then to compare the institutions in order to identify best practices., Materials and Methods: We conduct a multicentre, international clinical audit of six comprehensive cancer centres in Poland, Spain, Italy, Portugal, France, and Romania as a part of the project, known as IROCATES (Improving Quality in Radiation Oncology through Clinical Audits - Training and Education for Standardization)., Results: Radiotherapy practice varies from country to country, in part due to historical, economic, linguistic, and cultural differences. The institutions developed their own processes to suit their existing clinical practice., Conclusions: We believe that this study will contribute to establishing the value of routinely performing multi-institutional clinical audits and will lead to improvement of radiotherapy practice at the participating centres., Competing Interests: Conflict of interest None declared., (© 2023 Greater Poland Cancer Centre.)

Background: Cancer-associated fibroblasts (CAFs) are a diverse subset of cells, that is recently gaining in popularity and have the potential to become a new target for breast cancer (BC) therapy; however, broader research is required to understand their mechanisms and interactions with breast cancer cells. The goal of the study was to isolate CAFs from breast cancer tumour and characterise isolated cell lines. We concentrated on numerous CAF biomarkers that would enable their differentiation., Materials and Methods: Flow cytometry, immunofluorescence, and reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) were used to phenotype the primary CAFs., Results/conclusions: According to our findings, there was no significant pattern in the classification of cancer-associated fibroblasts. The results of biomarkers expression were heterogeneous, thus no specific subtypes were identified. Furthermore, a comparison of cancer-associated fibroblasts derived from different BC subtypes (luminal A and B, triple-negative, HER2 positive) did not reveal any clear trend of expression., Competing Interests: Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Greater Poland Cancer Centre.)

The first-order statistical (FOS) and second-order texture analysis on basis of Gray-Level Co-occurence Matrix (GLCM) were obtained to assess metabolic, volumetric, statistical and radiomic parameters of cervical cancer in response to chemotherapy, recurrence and age of patients. The homogeneous group of 83 patients with histologically confirmed IIIC1-IVB stage cervical cancer were analyzed, retrospectively. Before and after chemotherapy, the advancement of the disease and the effectiveness of the therapy, respectively, were established using [ 18 F] FDG PET/CT imaging. The statistically significant differences between pre- and post-therapy parameters were observed for SUV max , SUV mean , TLG, MTV, asphericity (ASP, p = 0.000, Z > 0), entropy (E, p = 0.0000), correlation (COR, p = 0.0007), energy (En, p = 0.000) and homogeneity (H, p = 0.0018). Among the FOS parameters, moderate correlation was observed between pre-treatment coefficient of variation (COV) and patients' recurrence (R = 0.34, p = 0.001). Among the GLCM textural parameters, moderate positive correlation was observed for post-treatment contrast (C) with the age of patients (R = 0.3, p = 0.0038) and strong and moderate correlation was observed in the case of En and H with chemotherapy response (R = 0.54 and R = 0.46, respectively). All correlations were statistically significant. This study indicates the remarkable importance of pre- and post-treatment [ 18 F] FDG PET statistical and textural GLCM parameters according to prediction of recurrence and chemotherapy response of cervical cancer patients., (© 2023. The Author(s).)

Modern communication and information technologies are rapidly being deployed at health care institutions around the world. Although these technologies offer many benefits, ensuring data protection is a major concern, and implementation of robust data protection measures is essential. In this context, health care providers and medical care facilities must frequently make difficult decisions and compromises between the need to provide effective medical care and the need to ensure data security and patient privacy. In the present paper, we describe and discuss key issues related to data protection systems in the setting of cancer care hospitals in Europe. We provide real-life examples from two European countries-Poland and the Czech Republic-to illustrate data protection issues and the steps being taking to address these questions. More specifically, we discuss the legal framework surrounding data protection and technical aspects related to patient authentication and communication.

Aim: In the treatment of prostate cancer with radiation therapy, the addition of a simultaneous integrated boost (SIB) to the dominant intraprostatic lesions (DIL) may improve local control. In this study, we aimed to determine the optimal radiation strategy in a phantom model of prostate cancer using volumetric modulated arc therapy for stereotactic body radiotherapy (SBRT-VMAT) with a SIB of 1-4 DILs., Methods: We designed and printed a three-dimensional anthropomorphic phantom pelvis to simulate individual patient structures, including the prostate gland. A total of 36.25 Gy (SBRT) was delivered to the whole prostate. The DILs were irradiated with four different doses (40, 45, 47.5, and 50 Gy) to assess the influence of different SIB doses on dose distribution. The doses were calculated, verified, and measured using both transit and non-transit dosimetry for patient-specific quality assurance using a phantom model., Results: The dose coverage met protocol requirements for all targets. However, the dose was close to violating risk constraints to the rectum when four DILs were treated simultaneously or when the DILs were located in the posterior segments of the prostate. All verification plans passed the assumed tolerance criteria., Conclusions: Moderate dose escalation up to 45 Gy seems appropriate in cases with DILs located in posterior prostate segments or if there are three or more DILs located in other segments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Skrobala, Kruszyna-Mochalska, Graczyk, Ryczkowski, Fundowicz, Milecki and Malicki.)

Background: Opioid-involved overdose continues to rise, largely explained by fentanyl adulteration of the illicit opioid supply. Fentanyl test strips are a novel drug checking tool that can be used by people who use drugs to detect the presence of fentanyl in drug products. However, it is unclear whether fentanyl test strip use can prompt behavior changes that impact risk of overdose., Methods: In this mixed-methods study involving a structured survey (n = 341) of syringe service program clients in southern Wisconsin, we examined the association between fentanyl test strip use and overdose risk behaviors in scenarios where the presence of fentanyl is confirmed and unknown. Individual items were transformed into summary scales representing the performance of riskier and safer behaviors. Linear regression examined the association of behaviors with FTS use. Models are adjusted for study site, race/ethnicity, age, gender, drug of choice, indicator of polysubstance use, times used per day, and lifetime overdose count., Results: In response to survey questions before prompting about fentanyl risk, people who used fentanyl test strips reported an increased number of safer (p = 0.001) as well as riskier behaviors (p = 0.018) relative to people who did not use fentanyl test strips. The same held true in situations when fentanyl adulteration was suspected, though fentanyl test strip use lost significance in the fully adjusted model examining safer behaviors (safer: p = 0.143; riskier: p = 0.004). Among people who use fentanyl test strips, in unadjusted models, a positive test result was associated with more safer behaviors and fewer riskier behaviors, but these associations became nonsignificant in fully adjusted models (safer: p = 0.998; riskier: p = 0.171). Loss of significance was largely due to the addition of either polysubstance use or age to the model., Conclusions: Fentanyl test strip use is associated with behaviors that may impact overdose risk, including safer and riskier behaviors. Specifically, a positive test result may promote more risk reducing behaviors and fewer risk enhancing behaviors than a negative test result. Results suggest that while FTS may promote safer drug use behaviors, outreach and education should emphasize the need for multiple harm reduction techniques in all scenarios., (© 2023. The Author(s).)

Background: Fentanyl adulteration of illicit drugs is a major driver of opioid-involved overdose in the USA. Fentanyl test strips are increasingly used by people who use drugs to check for fentanyl. However, little is known about factors that influence test strip use in this population., Methods: In this mixed-methods study employing semi-structured open-ended interviews (n = 29) and a structured survey (n = 341), we examined characteristics associated with test strip use, characteristics of test strip use, and situational, logistical and psychosocial factors influencing test strip use. Respondents were recruited from a syringe service program in southern Wisconsin. Bivariate tests of association and multivariable logistic regression examined the relationship between respondent characteristics and test strip use. Summary statistics were used to describe how situational, logistical and psychosocial factors impact test strip use., Results: Most respondents were male (59.6%), non-Hispanic white (77.4%), young (mean 35.7 years), reported heroin as their primary drug (70.7%), injection as their primary route (87.9%), and use ≥ 3 times daily (78.6%). In multivariable models, site, race and ethnicity, drug of choice, and seeking fentanyl were associated with test strip use. Among test strip users, 36.5% use them most of the time or more and 80.6% get positive results half the time or more. Among individuals reporting heroin, fentanyl, methamphetamine, or cocaine or crack cocaine at least once per month, 99.1%, 56.8%, 42.2%, and 55.7% reported testing these drugs, respectively. Test strip use is supported by information from suppliers, regular transportation, diverse distribution locations, recommendations from harm reduction staff, and having a safe or private place to use., Conclusions: We found that individuals who use fentanyl test strips are more often non-Hispanic white, use heroin, and seek drugs with fentanyl relative to individuals without test strip use. Findings confirm high fentanyl penetration in the Wisconsin drug supply. Low rates of stimulant testing suggest inadequate awareness of fentanyl penetration. Findings support outreach to key populations, increased diversity of distributing locations, efforts to correct misperceptions about drug wasting, emphasis on pre-consumption testing, and the importance of adjunct behaviors to prevent overdose given high rates of intentional fentanyl use., (© 2022. The Author(s).)

Since the introduction of computed tomography for planning purposes in the 1970s, we have been observing a continuous development of different imaging methods in radiotherapy. The current achievements of imaging technologies in radiotherapy enable more than just improvement of accuracy on the planning stage. Through integrating imaging with treatment machines, they allow advanced control methods of dose delivery during the treatment. This article reviews how the integration of existing and novel forms of imaging changes radiotherapy and how these advances can allow a more individualised approach to cancer therapy. We believe that the significant challenge for the next decade is the continued integration of a range of different imaging devices into linear accelerators. These imaging modalities should show intra-fraction changes in body morphology and inter-fraction metabolic changes. As the use of these more advanced, integrated machines grows, radiotherapy delivery will become more accurate, thus resulting in better clinical outcomes: higher cure rates with fewer side effects., Competing Interests: Conflict of interest None declared., (© 2022 Greater Poland Cancer Centre.)

Cancer-associated fibroblasts are a highly heterogeneous group of cells whose phenotypes and gene alterations are still under deep investigation. As a part of tumor microenvironment, they are the focus of a growing number of studies. Cancer-associated fibroblasts might become a new target of breast cancer therapy, but still more tests and analyses are needed to understand mechanisms and interactions between them and breast cancer cells. The study aimed to isolate cancer associated fibroblasts from breast cancer tissue and to phenotype the isolated cell lines. We focused on various cancer-associated fibroblast characteristic biomarkers and those that might differentiate various cancer-associated fibroblasts' subtypes. Patients with a histological diagnosis of invasive breast cancer (diameter ≤15 mm) and qualified for primary surgical treatment were enrolled in the study. Cell lines were isolated from breast cancer biopsy. For the phenotyping, we used flow cytometry, immunofluorescence and RT-qPCR analysis. Based on our study, there was no indication of a clear pattern in the cancer-associated fibroblasts' classification. Results of cancer-associated fibroblasts expression were highly heterogeneous, and specific subtypes were not defined. Moreover, comparing cancer-associated fibroblasts divided into groups based on BC subtypes from which they were isolated also did not allow to notice of any clear pattern of expressions. In the future, a higher number of analyzed cancer-associated fibroblast cell lines should be investigated to find expression schemes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (AJCR Copyright © 2022.)

Gastric cancer (GC) is the fourth most common cancer in the world in terms of incidence and second in terms of mortality. Chemotherapy is the main treatment for GC. The greatest challenge and major cause of GC treatment failure is resistance to chemotherapy. As such, research is ongoing into molecular evaluation, investigating mechanisms, and screening therapeutic targets. Several mechanisms related to both the tumor cells and the tumor microenvironment (TME) are involved in resistance to chemotherapy. TME promotes the secretion of various inflammatory cytokines. Recent studies have revealed that inflammatory cytokines affect not only tumor growth, but also chemoresistance. Cytokines in TME can be detected in blood circulation and TME cells. Inflammatory cytokines could serve as potential biomarkers in the assessment of chemoresistance and influence the management of therapeutics in GC. This review presents recent data concerning research on inflammatory cytokines involved in the mechanisms of chemoresistance and provides new clues in GC treatment.

In clinical radiotherapy, the most important aspects are the dose distribution in the target volume and healthy organs, including out-of-field doses in the body. Compared to photon beam radiation, dose distribution in electron beam radiotherapy has received much less attention, mainly due to the limited range of electrons in tissues. However, given the growing use of electron intraoperative radiotherapy and FLASH, further study is needed. Therefore, in this study, we determined out-of-field doses from an electron beam in a phantom model using two dosimetric detectors (diode E and cylindrical Farmer-type ionizing chamber) for electron energies of 6 MeV, 9 MeV and 12 MeV. We found a clear decrease in out-of-field doses as the distance from the field edge and depth increased. The out-of-field doses measured with the diode E were lower than those measured with the Farmer-type ionization chamber at each depth and for each electron energy level. The out-of-field doses increased when higher energy megavoltage electron beams were used (except for 9 MeV). The out-of-field doses at shallow depths (1 or 2 cm) declined rapidly up to a distance of 3 cm from the field edge. This study provides valuable data on the deposition of radiation energy from electron beams outside the irradiation field.

Hypo-fractionated stereotactic body radiation therapy (SBRT) is an effective treatment for prostate cancer (PCa). Although many studies have investigated the effects of SBRT on the prostate and adjacent organs, little is known about the effects further out-of-field. The aim of this study was to investigate, both in vitro and in a quasi-humanoid phantom, the biological effects (using a dose-scaling approach) of radiation in the out-of-field peripheral organs delivered by 6 MV volumetric modulated arc therapy (VMAT) SBRT in a prostate cancer model. Healthy prostate cells were irradiated in a phantom at locations corresponding to the prostate, intestine, lung, thyroid, and brain. Seven 10 Gy fractions of VMAT SBRT were delivered to the target in a single session without intermission (scaled-up method). Radiochromic films were used to measure the doses. The radiobiological response was assessed by measuring DNA breaks, the cell survival fraction, and differences in gene expression profile. Our results showed a strong, multiparametric radiobiological response of the cells in the prostate. Outside of the radiation field, the highest doses were observed in the intestine and lung. A small increase (not statistically significant) in DNA damage and cell death was observed in the intestines. Several gene groups (cell cycle, DNA replication) were depleted in the lung and thyroid (DNA replication, endocytosis), but further analysis revealed no changes in the relevant biological processes. This study provides extensive evidence of the types and extent of radiobiological responses during VMAT SBRT in a prostate cancer model. Additional research is needed to determine whether the radiobiological effects observed in the peripheral organs are validated in a clinical context.

FLASH radiotherapy (RT) is a technique involving the delivery of ultra-high dose rate radiation to the target. FLASH-RT has been shown to reduce radiation-induced toxicity in healthy tissues without compromising the anti-cancer effects of treatment compared to conventional radiation therapy. In the present article, we review the published data on FLASH-RT and discuss the current state of knowledge of this novel approach. We also highlight the technological constraints and complexity of FLASH-RT and describe the physics underlying this modality, particularly how technology supports energy transfer by ionising radiation (e.g., beam on/off sequence, pulse-energy load, intervals). We emphasise that current preclinical experience is mostly based on FLASH electrons and that clinical application of FLASH-RT is very limited. The incorporation of FLASH-RT into routine clinical radiotherapy will require the development of devices capable of producing FLASH photon beams., Competing Interests: Conflicts of interest None declared., (© 2022 Greater Poland Cancer Centre.)

No clear criteria have yet been established to guide decision-making for patient selection and the optimal timing of adaptive radiotherapy (ART) based on image-guided radiotherapy (IGRT). We have developed a novel protocol—the Best for Adaptive Radiotherapy (B-ART) protocol—to guide patient selection for ART. The aim of the present study is to describe this protocol, to evaluate its validity in patients with head and neck (HN) cancer, and to identify the anatomical and clinical predictors of the need for replanning. We retrospectively evaluated 82 patients with HN cancer who underwent helical tomotherapy (HT) and subsequently required replanning due to soft tissue changes upon daily MVCT. Under the proposed criteria, patients with anatomical changes >3 mm on three to four consecutive scans are candidates for ART. We compared the volumes on the initial CT scan (iCT) and the replanning CT (rCT) scan for the clinical target volumes (CTV1, referring to primary tumor or tumor bed and CTV2, metastatic lymph nodes) and for the parotid glands (PG) and body contour (B-body). The patients were stratified by primary tumor localization, clinical stage, and treatment scheme. The main reasons for replanning were: (1) a planning target volume (PTV) outside the body contour (n = 70; 85.4%), (2) PG shrinkage (n = 69; 84.1%), (3) B-body deviations (n = 69; 84.1%), and (4) setup deviations (n = 40; 48.8%). The replanning decision was made, on average, during the fourth week of treatment (n = 47; 57.3%). The mean reductions in the size of the right and left PG volumes were 6.31 cc (20.9%) and 5.98 cc (20.5%), respectively (p < 0.001). The reduction in PG volume was ≥30% in 30 patients (36.6%). The volume reduction in all of the anatomical structures was statistically significant. Four variables—advanced stage disease (T3−T4), chemoradiation, increased weight loss, and oropharyngeal localization—were significantly associated with the need for ART. The B-ART protocol provides clear criteria to eliminate random errors, and to allow for an early response to relevant changes in target volumes.

The aim of the study was to determine the influence of a key treatment plan and beam parameters on overall dose distribution and on doses in organs laying in further distance from the target during prostate SBRT. Multiple representative treatment plans (n = 12) for TrueBeam and CyberKnife were prepared and evaluated. Nontarget doses were measured with anionization chamber, in a quasi-humanoid phantom at four sites corresponding to the intestines, right lung, thyroid, and head. The following parameters were modified: radiotherapy technique, presence or not of a flattening filter, degree of modulation, and use or not of jaw tracking function for TrueBeam and beam orientation set-up, optimization techniques, and number of MUs for CyberKnife. After usual optimization doses in intestines (near the target) were 0.73% and 0.76%, in head (farthest from target) 0.05% and 0.19% for TrueBeam and CyberKnife, respectively. For TrueBeam the highest peripheral (head, thyroid, lung) doses occurred for the VMAT with the flattening filter while the lowest for 3DCRT. For CyberKnife the highest doses were for gantry with caudal direction beams blocked (gantry close to OARs) while the lowest was the low modulated VOLO optimization technique. The easiest method to reduce peripheral doses was to combine FFF with jaw tracking and reducing monitor units at TrueBeam and to avoid gantry position close to OARs together with reduction of monitor units at CyberKnife, respectively. The presented strategies allowed to significantly reduce out-of-field and nontarget doses during prostate radiotherapy delivered with TrueBeam and CyberKnife. A different approach was required to reduce peripheral doses because of the difference in dose delivery techniques: non-coplanar using CyberKnife and coplanar using TrueBeam, respectively.

Purpose: One of the main challenges in facial region brachytherapy is fixation of vendor-delivered standard applicators. Reproducibility can be maintained; however, there are frequent problems with applicator fitting to the skin surface in pleated regions. Manually prepared individual moulds require technological facilities and highly-trained staff. This article presents 3D-printed applicator preparation for a particular patient skin brachytherapy, using low-cost equipment and free software. We described applicator preparation in a step-by-step workflow., Material and Methods: This study demonstrated preparation of a skin brachytherapy applicator for a challenging recurrent tumor located in the nose bridge. During first visit of patient, fiducial markers were placed to enclose treated region. Patient was computed tomography (CT)-scanned, and reconstruction of target volume and surrounding organs at risk (OARs) were performed using treatment planning system (TPS). In TPS on patient's surface, a 1-cm thick bolus was added as a body of applicator. Inside the bolus, source paths were designed, and pre-plan was prepared. Using Beben - DICOM to standard triangle language (STL) software, the body of applicator and source-paths from pre-planning was transformed into an STL file, which was used as a solid definition in 3D printing., Results: The printed applicator fitted very well, and its' placement was quickly consistent regarding placing and securing. CTV was slightly broader in treatment plan (0.34 cm 3 vs. 0.31 cm 3 ), and doses given to CTV were lower, except for V 150 , which was higher for the realized plan (1.15% vs. 1.83%). All reported doses to OARs were lower in the realized plan., Conclusions: A low-cost 3D printer and widely available PLA filaments seem feasible to produce individual contact applicators for skin brachytherapy. Beben - DICOM to STL software and presented workflow appear to be convenient and simple tool., Competing Interests: The authors and related institutions do not guarantee 100% security of the proposed solutions. We call for a review of the presented conduct path and subject the given procedure to all available quality control measures. The authors and related institutions do not take any responsibility for clinical application of the presented solutions. There is no conflict of interests to declare.The authors report no conflict of interest., (Copyright © 2022 Termedia.)

Our understanding of low dose, out-of-field radiation and their radiobiological effects are limited, in part due to the rapid technological advances in external beam radiotherapy, especially for non-coplanar and dynamic techniques. Reliable comparisons of out-of-field doses produced by advanced radiotherapy techniques are difficult due to the limitations of commercially available phantoms. There is a clear need for a functional phantom to accurately measure the dosimetric and radiobiological characteristics of out-of-field doses, which would in turn allow clinicians and medical physicists to optimize treatment parameters. We designed, manufactured, and tested the performance of a quasi-humanoid (Q-H) adult phantom. To test the physics parameters, we used computed tomography (CT) scans of assembled Q-H phantom. Static open field and dynamic techniques were measured both in- and out-of-field with ionization chambers and radiochromic films for two configurations (full solid and with water-filled containers). In the areas simulating soft tissues, lung, and bones, median Hounsfield units and densities were, respectively: 129.8, -738.7, 920.8 HU and 1.110, 0.215, 1.669 g/cm 3 . Comparison of the measured to treatment planning systems (TPS) in-field dose values for the sample volumetric arc therapy (VMAT) (6 MV flattening filter-free (FFF)) plan, 96.4% of analyzed points passed the gamma evaluation criteria (L2%/2 mm, threshold (TH) 10%) and less than 1.50% for point dose verification. In the two phantom configurations: full poly(methyl) methacrylate (PMMA) and with water container, the off-axis median doses for open field, relative to the central axis of the beam (CAX) were similar, respectively: 0.900% versus 0.907% (15 cm distance to CAX); 0.096% versus 0.120% (35 cm); 0.018% versus 0.018% (52 cm); 0.009% versus 0.008% (74 cm). For VMAT 6 MV FFF, doses relative the CAX were, respectively: 0.667% (15 cm), 0.062% (35 cm), 0.019% (52 cm), 0.016% (74 cm). The Q-H phantom meets the International Commission on Radiation Units and Measurements (ICRU) and American Association of Physicists in Medicine (AAPM) recommended phantom criteria, providing medical physicists with a reliable, comprehensive system to perform dose calculation and measurements and to assess the impact on radiobiological response and on the risk of secondary tumor induction., (© 2022 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, LLC on behalf of The American Association of Physicists in Medicine.)

(1) Current breast-conserving therapy for breast cancer consists of a combination of many consecutive treatment modalities. The most crucial goal of postoperative treatment is to eradicate potentially relapse-forming residual cancerous cells within the tumor bed. To achieve this, the HDR brachytherapy boost standardly added to external beam radiotherapy was enhanced with an initial thermal boost. This study presents an original thermal boost technique developed in the clinic. (2) A detailed point-by-point description of thermal boost application is presented. Data on proper patient selection, microwave thermal boost planning, and interstitial hyperthermia treatment delivery are supported by relevant figures and schemes. (3) Out of 1134 breast cancer patients who were administered HDR brachytherapy boost in the tumor bed, 262 were also pre-heated interstitially without unexpected complications. The results are supported by two example cases of hyperthermia planning and delivery. (4) Additional breast cancer interstitial thermal boost preceding HDR brachytherapy boost as a part of combined treatment in a unique postoperative setting was feasible, well-tolerated, completed in a reasonable amount of time, and reproducible. A commercially available interstitial hyperthermia system fit and worked well with standard interstitial brachytherapy equipment.

The current situation and management of Ukrainian patients at 2 European cancer care centers in Poland and Italy is described. Both centers admit refugees from the war in Ukraine., (© 2022 The Authors.)

Background: 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., Materials and Methods: 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., Results: 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) vs . VMAT and IMRT (34.6-38.76 Gy). The mean dose to the rectum (V36Gy, mm 3 ) was significantly lower (p < 0.001) in the CK plans (219.78 vs . 519.59 and 422.62, respectively). The mean bladder dose (V37Gy, mm 3 ) was significantly greater for CK (3256 vs . 1090.75 for VMAT and 4.5 for IMRT (p < 0.001). CK yielded significantly better CI (1.07 vs . 1.17 and 1.25 for VMAT and IMRT, respectively; p < 0.01) and HI values (1.27 vs . 1.07 and 1.04; p < 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., Conclusions: 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., (© 2022 Dorota Maria Borowicz, Agnieszka Skrobała, Marta Kruszyna-Mochalska, Julian Malicki, published by Sciendo.)

Recent comparison of an ultra-hypofractionated radiotherapy (UF-RT) boost to a conventionally fractionated (CF-RT) option showed similar toxicity and disease control outcomes. An analysis of the treatment plans for these patients is needed for evaluating calculated doses for different organs, treatment beam-on time, and requirements for human and financial resources. Eighty-six plans for UF-RT and 93 plans for CF-RT schemes were evaluated. The biologically equivalent dose, EQD2, summed for the first phase and the boost, was calculated for dose-volume parameters for organs at risk (OARs), as well as for the PTV1. ArcCHECK measurements for the boost plans were used for a comparison of planned and delivered doses. Monitor units and beam-on times were recorded by the Eclipse treatment planning system. Statistical analysis was performed with a significance level of 0.05. Dosimetric parameter values for OARs were well within tolerance for both groups. EQD2 for the PTV1 was on average 84 Gy for UF-RT patients and 76 Gy for CF-RT patients. Gamma passing rate for planned/delivered doses comparison was above 98% for both groups with 3 mm/3% distance to agreement/dose difference criteria. Total monitor units per fraction were 647 ± 94 and 2034 ± 570 for CF-RT and UF-RT, respectively. The total delivery time for boost radiation for the patients in the UF-RT arm was, on average, four times less than the total time for a conventional regimen with statistically equal clinical outcomes for the two arms in this study.

Background: The availability of linear accelerators (linac) for research purposes is often limited and therefore alternative radiation sources are needed to conduct radiobiological research. The National Centre for Radiation Research in Poland recently developed an intraoperative mobile linac that enables electron irradiation at energies ranging from 4 to 12 MeV and dose rates of 5 or 10 Gy/min. The present study was conducted to evaluate the electron beam parameters of this intraoperative linac and to verify the set-up to evaluate out-of-field doses in a water phantom, which were determined through dosimetric and biological response measurements., Materials and Methods: The distribution of radiation doses along and across the radiation beam were measured in a water phantom using a semiconductor detector and absolute doses using an ionisation chamber. Two luminal breast cancer cell lines (T-47D and HER2 positive SK-BR-3) were placed in the phantom to study radiation response at doses ranging from 2 to 10 Gy. Cell response was measured by clonogenic assays., Results and Conclusion: The electron beam properties, including depth doses and profiles, were within expected range for the stated energies. These results confirm the viability of this device and set-up as a source of megavoltage electrons to evaluate the radiobiological response of tumour cells., Competing Interests: Conflicts of interest None declared., (© 2021 Greater Poland Cancer Centre.)

Few studies have directly compared passive scattering (PS) to intensity-modulated proton therapy (IMPT) in the delivery of ultra-hypofractionated proton beams to the localized prostate cancer (PCa). In this preliminary study involving five patients previously treated with CyberKnife, treatment plans were created for PS and IMPT (36.25 CGE in five fractions with two opposing fields) to compare the dosimetric parameters to the planning target volume (PTV) and organs-at-risk (OAR: rectum, bladder, femoral heads). Both plans met the acceptance criteria. Significant differences were observed in the minimum and maximum doses to the PTV. The mean dose to the PTV was lower for PS (35.62 ± 0.26 vs. 37.18 ± 0.14; p = 0.002). Target coverage (D98%) was better for IMPT (96.79% vs. 99.10%; p = 0.004). IMPT resulted in significantly lower mean doses to the rectum (16.75 CGE vs. 6.88 CGE; p = 0.004) and bladder (17.69 CGE vs. 5.98 CGE p = 0.002). High dose to the rectum (V36.25 CGE) were lower with PS, but not significantly opposite to high dose to the bladder. No significant differences were observed in mean conformity index values, with a non-significant trend towards higher mean homogeneity index values for PS. Non-significant differences in the gamma index for both fields were observed. These findings suggest that both PS and IMPT ultra-hypofractionated proton therapy for PCa are highly precise, offering good target coverage and sparing of normal tissues and OARs.

Purpose: Brachytherapy is a great alternative for restrictive surgical procedures in facial cancers. Moreover, dose distribution is more beneficial compared with teleradiotherapy during treatment of lesions located on anatomical curves. However, repetitiveness of application is the main issue associated with using commercial applicators. The risk of its displacement is very unfavorable due to large dose gradients in brachytherapy. The aim of this study was to develop a process of preparation of applicators using 3D printing technology., Material and Methods: In planning system, circular volumes near the nose, eye, and ear were determined on transverse layers of an anthropomorphic phantom. Next, boluses with a thickness of 5 mm and 10 mm were designed for each of the layers. Channels in the 10 mm bolus were designed in such a way to place the catheters into the layers. Prepared applicators were printed using polylactic acid (PLA) filament. Plans to irradiate the films for their calibration and plans for treatment prepared in the treatment planning system were conducted. A special phantom was created to calibrate the radiochromic films. Dose distribution around the designed applicators was measured in an anthropomorphic phantom using films within the layers of phantom. Comparison of doses was performed with two-dimensional gamma analysis using OmniPro I'mRT software., Results: The obtained results confirmed compliance of the planned and measured doses in 92%; the analysis of gamma parameter showed 1%/1 mm for acceptability level of 95%. Moreover, the initial dosimetric analysis for gamma criteria with 2%/2 mm showed compliance at 99%., Conclusions: The results of the present study confirm potential clinical usefulness of the applicators obtained with the use of 3D printing for brachytherapy., Competing Interests: The authors report no conflict of interest., (Copyright © 2021 Termedia.)