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BACKGROUND: Despite the global increase in older employees, workplace physical activity interventions (WPAIs) for this target group have not yet been sufficiently developed. The major drawback of existing WPAIs is low adherence due to lack of time or limited motivation. A novel approach could be to integrate tailored neuromotor and strength exercises into everyday working tasks to prevent the functional decline of older employees at the workplace without needing much additional time for training. This approach was tested in the present study by evaluating the proof-of-concept of a novel WPAI based on the Lifestyle-integrated Functional Exercise (LiFE) program integrated into a working environment (wLiFE55 +). METHODS: The proof-of-concept of wLiFE55 + was quantified within a 4-week pre-post exercise intervention study by measuring (1) feasibility including adherence, activity frequency, adverse events and acceptance (integrability of wLiFE55 + activities, perceived improvement and safety, satisfaction, physical demand, personal trainer session, intervention content) and (2) pre-to-post changes in neuromotor function (12-Level Balance Scale, 12-LBS; Community Balance and Mobility Scale, CBM), strength (60sec Chair Stand Test), and PA (1-week activity monitoring). For statistical analysis, the median and interquartile range (IQR) were computed. For pre-to-post changes, Wilcoxon signed-rank tests with effect size (r) were also performed. RESULTS: Seventeen older employees (mean age 59 years, 8 female) were included of which fifteen completed the study. The intervention adherence was 100%, and the activity adherence was 58% (9 out of 12 maximum possible wLiFE55 + activities implemented). Depending on the specific activity, the frequency of practice ranged between 25-75% of the days of the intervention period, and single wLiFE55 + activities were practiced between one and three times per day. No adverse events occurred, and acceptance was high. Pre-to-post increases with medium effect sizes were found for neuromotor function (CBM, 12-LBS) and specific PA variables (total sedentary time, sedentary bouts > 30 min). CONCLUSION: The results of the study highlight the feasibility of wLiFE55 + in a work setting with older employees. The pre-to-post increases observed in neuromotor measures and reductions in sedentary time suggest that wLiFE55 + may counteract the age-related functional decline in older employees and justifies future studies in this field. The next steps are program adjustments to boost exercise frequency and evaluating wLiFE55 + in a randomized controlled trial.
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Backgrounds/Aims: Although access to proton beam therapy (PBT) is limited worldwide, its use for the treatment of hepatocellular carcinoma (HCC) is gradually increasing with the expansion of new facilities. Therefore, we conducted a systematic review and meta-analysis to investigate the updated evidence of PBT for HCC. Methods: The MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were systematically searched for studies that enrolled patients with liver-confined HCC that were treated with PBT for a cure up to February 2024. Results: A total of 1858 HCC patients receiving PBT from 22 studies between 2004 and 2023 were selected for this meta-analysis. The median proportion of Child-Pugh class A was 86% (range: 41-100%), and the median tumor size was 3.6 cm (range: 1.2-9 cm). The median total dose ranged from 55 GyE to 76 GyE (median, 69 GyE). The pooled rates of 3- and 5-year local progression-free survival after PBT were 88% (95% confidence interval [CI], 85-91%) and 86% (95% CI, 82-90%), respectively. The pooled 3- and 5-year overall rates were 60% (95% CI, 54-66%) and 46% (95% CI, 38-54%), respectively. The pooled rates of grade 3 hepatic toxicity, classic radiation-induced liver disease (RILD), and non-classic RILD were 1%, 2%, and 1%, respectively. Conclusions: The current study supports PBT for HCC and demonstrates favorable long-term survival and low hepatic toxicities compared with other published studies on other radiotherapy modalities. However, further studies are needed to identify the subgroups that will benefit from PBT.
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PURPOSE: Stereotactic body radiotherapy (SBRT) has emerged as a promising new modality for locally advanced pancreatic cancer (LAPC). The current study evaluated the efficacy and toxicity of SBRT in patients with LAPC (NCT03648632). METHODS: This prospective single institution phase II study recruited patients with histologically or cytologically proven adenocarcinoma of the pancreas after more than two months of combination chemotherapy with no sign of progressive disease. Patients were prescribed 50-60 Gy in 5-8 fractions. Patients were initially treated on a standard linac (n = 4). Since 2019, patients were treated using online magnetic resonance (MR) image-guidance on a 1.5 T MRI-linac, where the treatment plan was adapted to the anatomy of the day. The primary endpoint was resection rate. RESULTS: Twenty-eight patients were enrolled between August 2018 and March 2022. All patients had non-resectable disease at time of diagnosis. Median follow-up from inclusion was 28.3 months (95 % CI 24.0-NR). Median progression-free and overall survival from inclusion were 7.8 months (95 % CI 5.0-14.8) and 16.5 months (95 % CI 10.7-22.6), respectively. Six patients experienced grade III treatment-related adverse events (jaundice, nausea, vomiting and/or constipation). One of the initial four patients receiving treatment on a standard linac experienced a grade IV perforation of the duodenum. Six patients (21 %) underwent resection. A further one patient was offered resection but declined. CONCLUSION: This study demonstrates that SBRT in patients with LAPC was associated with promising overall survival and resection rates. Furthermore, SBRT was safe and well tolerated, with limited severe toxicities.
Subject(s)
Pancreatic Neoplasms , Radiosurgery , Humans , Radiosurgery/methods , Radiosurgery/adverse effects , Pancreatic Neoplasms/radiotherapy , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/diagnostic imaging , Male , Female , Aged , Middle Aged , Prospective Studies , Aged, 80 and over , Radiotherapy, Image-Guided/methods , Adenocarcinoma/pathology , Adenocarcinoma/radiotherapy , Adenocarcinoma/surgery , Adenocarcinoma/diagnostic imaging , Magnetic Resonance Imaging/methodsABSTRACT
Remote e-working with information and communication technology (ICT) has long been on the rise, with its implementation accelerated by mandatory working from home regulations during the COVID-19 pandemic. This systematic literature review summarises the influencing factors of ICT-based remote e-working (device types, duration of use, user interfaces, etc.) on the physical health (musculoskeletal system and eyes) of knowledge workers. A search in four electronic databases and a manual search in four German journals resulted in 21 articles being included in this review. A bias analysis was conducted for all articles. Unfavourable postures, inappropriate working devices and certain environmental factors may cause a range of physical complaints, even after comparably short periods of time. Mostly, these complaints are greater compared to those experienced when working on a fully equipped stationary computer. Therefore, remote e-working requires careful planning, awareness, and the willingness to embrace working situations that counteract these problems.
Different factors associated with remote e-working may influence physical health. This systematic literature review found that unfavourable postures, inappropriate working devices and certain environmental factors may cause physical complaints, even after short periods of time. Mostly, these complaints are greater compared to those experienced when working on a stationary computer.
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BACKGROUND: The research project GAIN (working healthy in inclusion companies) deals with the topics of health and work in inclusive companies. Due to a great need for research on (occupational) health (e.g. physical and mental health status) and workplace design in companies employing people with disabilities, this project pursues the primary goal of generating information for the development and implementation of health-preserving measures within the framework of occupational health and safety, and risk assessment, for employees with and without impairments in inclusive companies. METHODS: Within the framework of the project, the employees of three inclusive companies will be examined with the help of an interdisciplinary and triangulative approach. Using quantitative and qualitative methods, specific physical workloads and hazards will be investigated by means of baseline screening methods and measurement techniques, specifically among employees with physical disabilities and impairments. In the statistical analysis, descriptive methods will be used to record the current state, while inferential statistical methods will be used to evaluate health maintenance measures. Inferential statistics for continuous data with confidence intervals based on the statistical parametric mapping (SPM) method will also be performed. The significance level will be set at 5%. Qualitative methods will be used to analyse structures and working conditions within the companies, with particular attention to the specific construction of the relationship between work, health and disability. CONCLUSIONS: The structures in inclusion companies must be specifically designed to support and promote the understanding of work and health in relation to the idea of one's own body, its positioning in space and its performance. These characteristics are to be identified in the course of the project and bundled into best-practice recommendations. Furthermore, it is the aim of the research project to derive recommendations for action at its conclusion and to present further advice for the promotion of health in inclusive companies.
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Pancreatic cancer is rising as one of the leading causes of cancer-related death worldwide. Patients often present with advanced disease, limiting curative treatment options and therefore making management of the disease difficult. Systemic chemotherapy has been an established part of the standard treatment in patients with both locally advanced and metastatic pancreatic cancer. In contrast, the use of radiotherapy has no clear defined role in the treatment of these patients. With the evolving imaging and radiation techniques, radiation could become a plausible intervention. In this review, we give an overview over the available data regarding radiotherapy, chemoradiation, and stereotactic body radiation therapy. We performed a systematic search of Embase and the PubMed database, focusing on studies involving locally advanced pancreatic cancer (or non-resectable pancreatic cancer) and radiotherapy without any limitation for the time of publication. We included randomised controlled trials involving patients with locally advanced pancreatic cancer, including radiotherapy, chemoradiation, or stereotactic body radiation therapy. The included articles represented mainly small patient groups and had a high heterogeneity regarding radiation delivery and modality. This review presents conflicting results concerning the addition of radiation and modality in the treatment regimen. Further research is needed to improve outcomes and define the role of radiation therapy in pancreatic cancer.
Subject(s)
Adenocarcinoma , Pancreatic Neoplasms , Radiosurgery , Humans , Pancreatic Neoplasms/radiotherapy , Pancreatic Neoplasms/drug therapy , Adenocarcinoma/radiotherapy , Adenocarcinoma/drug therapy , Chemoradiotherapy/methods , Radiosurgery/methods , Randomized Controlled Trials as Topic , Pancreatic NeoplasmsABSTRACT
BACKGROUND: According to current evidence, the best treatment for fit patients with non-resectable pancreatic cancer (PC) is combination chemotherapy, whereas frail patients are recommended gemcitabine (Gem) monotherapy. Randomized controlled trials in colorectal cancer and a post-hoc analysis of gemcitabine and nab-paclitaxel (GemNab) in PC suggest, however, that reduced dose of combination chemotherapy may be feasible and more efficient compared to monotherapy in frail patients. The aim of this study is to investigate whether reduced dose GemNab is superior to full dose Gem in patients with resectable PC, who are not candidates for full dose combination chemotherapy in first line. METHODS: The Danish Pancreas Cancer Group (DPCG)-01 trial is a national multicenter prospective randomized phase II trial. A total of 100 patients in ECOG performance status 0-2 with non-resectable PC, not candidate for full dose combination chemotherapy in first line, but eligible for full dose Gem, will be included. Patients are randomized 1:1 to either full dose Gem or GemNab in 80% of recommended dose. The primary endpoint is progression-free survival. Secondary endpoints are overall survival, overall response rate, quality of life, toxicity and rate of hospitalizations during treatment. The correlation between blood inflammatory markers, including YKL-40 and IL-6, circulating tumor DNA, and tissue biomarkers of resistance to chemotherapy and outcome will be explored. Finally, the study will include measures of frailty (G8, modified G8, and chair-stand-test) to assess whether scoring would enable a personalized allocation to different treatments or indicates a possibility for interventions. DISCUSSION: Single-drug treatment with Gem has for frail patients with non-resectable PC been the main treatment option for more than thirty years, but the impact on outcome is modest. If improved results and sustained tolerability with reduced dose combination chemotherapy can be shown, this could change the future practice for this increasing group of patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05841420. Secondary Identifying No: N-20210068. EudraCT No: 2021-005067-52. PROTOCOL VERSION: 1.5, 16-MAY-2023.
Subject(s)
Gemcitabine , Pancreatic Neoplasms , Humans , Deoxycytidine , Quality of Life , Prospective Studies , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Pancreatic Neoplasms/pathology , Paclitaxel , Albumins , Randomized Controlled Trials as Topic , Pancreatic NeoplasmsABSTRACT
Background: Pencil beam scanning (PBS) proton therapy can provide highly conformal target dose distributions and healthy tissue sparing. However, proton therapy of hepatocellular carcinoma (HCC) is prone to dosimetrical uncertainties induced by respiratory motion. This study aims to develop intra-treatment tumor motion monitoring during respiratory gated proton therapy and combine it with motion-including dose reconstruction to estimate the delivered tumor doses for individual HCC treatment fractions. Methods: Three HCC-patients were planned to receive 58 GyRBE (n=2) or 67.5 GyRBE (n=1) of exhale respiratory gated PBS proton therapy in 15 fractions. The treatment planning was based on the exhale phase of a 4-dimensional CT scan. Daily setup was based on cone-beam CT (CBCT) imaging of three implanted fiducial markers. An external marker block (RPM) on the patient's abdomen was used for exhale gating in free breathing. This study was based on 5 fractions (patient 1), 1 fraction (patient 2) and 6 fractions (patient 3) where a post-treatment control CBCT was available. After treatment, segmented 2D marker positions in the post-treatment CBCT projections provided the estimated 3D motion trajectory during the CBCT by a probability-based method. An external-internal correlation model (ECM) that estimated the tumor motion from the RPM motion was built from the synchronized RPM signal and marker motion in the CBCT. The ECM was then used to estimate intra-treatment tumor motion. Finally, the motion-including CTV dose was estimated using a dose reconstruction method that emulates tumor motion in beam's eye view as lateral spot shifts and in-depth motion as changes in the proton beam energy. The CTV homogeneity index (HI) The CTV homogeneity index (HI) was calculated as D 2 % - D 98 % D 50 % × 100 % . Results: The tumor position during spot delivery had a root-mean-square error of 1.3 mm in left-right, 2.8 mm in cranio-caudal and 1.7 mm in anterior-posterior directions compared to the planned position. On average, the CTV HI was larger than planned by 3.7%-points (range: 1.0-6.6%-points) for individual fractions and by 0.7%-points (range: 0.3-1.1%-points) for the average dose of 5 or 6 fractions. Conclusions: A method to estimate internal tumor motion and reconstruct the motion-including fraction dose for PBS proton therapy of HCC was developed and demonstrated successfully clinically.
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Objective: Growth hormone deficiency (GHD) is the most common endocrine late effect in irradiated survivors of childhood brain tumors. This study aimed to determine the prevalence of GHD in adults treated with proton or photon irradiation for a brain tumor in childhood and to detect undiagnosed GHD. Design: This study is a cross-sectional study. Methods: We investigated GHD in 5-year survivors from two health regions in Denmark treated for childhood brain tumors with cranial or craniospinal irradiation in the period 1997-2015. Medical charts were reviewed for endocrinological and other health data. Survivors without a growth hormone (GH) test at final height were invited to a GH stimulation test. Results: Totally 41 (22 females) survivors with a median age of 21.7 years (range: 15.1-33.8 years) at follow-up and 14.8 years (range: 5.1-23.4 years) since diagnosis were included; 11 were treated with proton and 30 with photon irradiation; 18 of 21 survivors were previously found to have GHD; 16 of 20 survivors with no GH test at final height were tested, 8 (50 %) had GHD. In total, 26 of 41 patients (63%) had GHD. Insulin-like growth factor-1 (IGF-1) is associated poorly with the insulin tolerance test (ITT). Conclusion: This study identified a high prevalence of undiagnosed GHD in survivors with no GH test at final height. The results stress the importance of screening for GHD at final height in survivors of childhood brain tumors with prior exposure to cranial irradiation, irrespective of radiation modality and IGF-1. Significance statement: This cross-sectional study reports a prevalence of 63% of GHD in irradiated childhood brain tumor survivors. Furthermore, the study identified a considerable number of long-term survivors without a GH test at final height, of whom, 50% subsequently were shown to have undiagnosed GHD. Additionally, this study confirmed that a normal serum IGF-1 measurement cannot exclude the diagnosis of GHD in irradiated survivors. This illustrates the need for improvements in the diagnostic approach to GHD after reaching final height in childhood brain tumor survivors at risk of GHD. In summary, our study stresses the need for GHD testing in all adult survivors treated with cranial irradiation for a brain tumor in childhood irrespective of radiation modality.
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AIM: Academic and high volume hospitals have better outcome for pancreatic cancer (PC) surgery, but there are no reports on oncological treatment. We aimed to determine the influence of facility types on overall survival (OS) after treatment with chemotherapy for inoperable PC. MATERIAL AND METHODS: 2,657 patients were treated in Denmark from 2012 to 2018 and registered in the Danish Pancreatic Cancer Database. Facilities were classified as either secondary oncological units or comprehensive, tertiary referral cancer centers. RESULTS: The average yearly number of patients seen at the four tertiary facilities was 71, and 31 at the four secondary facilities. Patients at secondary facilities were older, more frequently had severe comorbidity and lived in non-urban municipalities. As compared to combination chemotherapy, monotherapy with gemcitabine was used more often (59%) in secondary facilities than in tertiary (34%). The unadjusted median OS was 7.7 months at tertiary and 6.1 months at secondary facilities. The adjusted hazard ratio (HR) of 1.16 (confidence interval 1.07-1.27) demonstrated an excess risk of death for patients treated at secondary facilities, which disappeared when taking type of chemotherapy used into account. Hence, more use of combination chemotherapy was associated with the observed improved OS of patients treated at tertiary facilities. Declining HR's per year of first treatment indicated improved outcomes with time, however the difference among facility types remained significant. DISCUSSION: Equal access to modern combination chemotherapy at all facilities on a national level is essential to ensure equality in treatment results.
Subject(s)
Hospitals, High-Volume , Pancreatic Neoplasms , Drug Therapy, Combination , Humans , Pancreatic Neoplasms/drug therapy , Proportional Hazards Models , Retrospective StudiesABSTRACT
BACKGROUND AND PURPOSE: Patients with lower-grade gliomas are long-term survivors after radiotherapy and may benefit from the reduced dose to normal tissue achievable with proton therapy. Here, we aimed to quantify differences in dose to the uninvolved brain and contralateral hippocampus and compare the risk of radiation-induced secondary cancer for photon and proton plans for lower-grade glioma patients. MATERIALS AND METHODS: Twenty-three patients were included in this in-silico planning comparative study and had photon and proton plans calculated (50.4 Gy(RBE = 1.1), 28 Fx) applying similar dose constraints to the target and organs at risk. Automatically calculated photon plans were generated with a 3 mm margin from clinical target volume (CTV) to planning target volume. Manual proton plans were generated using robust optimisation on the CTV. Dose metrics of organs at risk were compared using population mean dose-volume histograms and Wilcoxon signed-rank test. Secondary cancer risk per 10,000 persons per year (PPY) was estimated using dose-volume data and a risk model for secondary cancer induction. RESULTS: CTV coverage (V95%>98%) was similar for the two treatment modalities. Mean dose (Dmean) to the uninvolved brain was significantly reduced from 21.5 Gy (median, IQR 17.1-24.4 Gy) with photons compared to 10.3 Gy(RBE) (8.1-13.9 Gy(RBE)) with protons. Dmean to the contralateral hippocampus was significantly reduced from 6.5 Gy (5.4-11.7 Gy) with photons to 1.5 Gy(RBE) (0.4-6.8 Gy(RBE)) with protons. The estimated secondary cancer risk was reduced from 6.7 PPY (median, range 3.3-10.4 PPY) with photons to 3.0 PPY (1.3-7.5 PPY) with protons. CONCLUSION: A significant reduction in mean dose to uninvolved brain and contralateral hippocampus was found with proton planning. The estimated secondary cancer risk was reduced with proton therapy.
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BACKGROUND: The Danish Neuro Oncology Group (DNOG) has established national consensus guidelines for the delineation of organs at risk (OAR) structures based on published literature. This study was conducted to finalise these guidelines and evaluate the inter-observer variability of the delineated OAR structures by expert observers. MATERIAL AND METHODS: The DNOG delineation guidelines were formed by participants from all Danish centres that treat brain tumours with radiotherapy. In a two-day workshop, guidelines were discussed and finalised based on a pilot study. Following this, the ten participants contoured the following OARs on T1-weighted gadolinium enhanced MRI from 13 patients with brain tumours: optic tracts, optic nerves, chiasm, spinal cord, brainstem, pituitary gland and hippocampus. The metrics used for comparison were the Dice similarity coefficient (Dice), mean surface distance (MSD) and others. RESULTS: A total of 968 contours were delineated across the 13 patients. On average eight (range six to nine) individual contour sets were made per patient. Good agreement was found across all structures with a median MSD below 1 mm for most structures, with the chiasm performing the best with a median MSD of 0.45 mm. The Dice was as expected highly volume dependent, the brainstem (the largest structure) had the highest Dice value with a median of 0.89 whereas smaller volumes such as the chiasm had a Dice of 0.71. CONCLUSION: Except for the caudal definition of the spinal cord, the variances observed in the contours of OARs in the brain were generally low and consistent. Surface mapping revealed sub-regions of higher variance for some organs. The data set is being prepared as a validation data set for auto-segmentation algorithms for use within the Danish Comprehensive Cancer Centre - Radiotherapy and potential collaborators.
Subject(s)
Organs at Risk , Radiotherapy Planning, Computer-Assisted , Brain/diagnostic imaging , Humans , Observer Variation , Pilot ProjectsABSTRACT
Compared to x-ray-based stereotactic body radiotherapy (SBRT) of liver cancer, proton SBRT may reduce the normal liver tissue dose. For an optimal trade-off between target and liver dose, a non-uniform dose prescription is often applied in x-ray SBRT, but lacks investigation for proton SBRT. Also, proton SBRT is prone to breathing-induced motion-uncertainties causing target mishit or dose alterations by interplay with the proton delivery. This study investigated non-uniform and uniform dose prescription in proton-based liver SBRT, including effects of rigid target motion observed during planning-4DCT and treatment. The study was based on 42 x-ray SBRT fractions delivered to 14 patients under electromagnetic motion-monitoring. For each patient, a non-uniform and uniform proton plan were made. The uniform plan was renormalized to be iso-toxic with the non-uniform plan using a NTCP model for radiation-induced liver disease. The motion data were used in treatment simulations to estimate the delivered target dose with rigid motion. Treatment simulations were performed with and without a repainting scheme designed to mitigate interplay effects. Including rigid motion, the achieved CTV mean dose after three fractions delivered without repainting was on average (±SD) 24.8 ± 8.4% higher and the D98%was 16.2 ± 11.3% higher for non-uniform plans than for uniform plans. The interplay-induced increase in D2%relative to the static plans was reduced from 3.2 ± 4.1% without repainting to -0.5 ± 1.7% with repainting for non-uniform plans and from 1.5 ± 2.0% to 0.1 ± 1.3% for uniform plans. Considerable differences were observed between estimated CTV doses based on 4DCT motion and intra-treatment motion. In conclusion, non-uniform dose prescription in proton SBRT may provide considerably higher tumor doses than uniform prescription for the same complication risk. Due to motion variability, target doses estimated from 4DCT motion may not accurately reflect the delivered dose. Future studies including modelling of deformations and associated range uncertainties are warranted to confirm the findings.
Subject(s)
Liver Neoplasms , Lung Neoplasms , Radiosurgery , Radiotherapy, Intensity-Modulated , Humans , Liver Neoplasms/radiotherapy , Lung Neoplasms/radiotherapy , Prescriptions , Protons , Radiosurgery/adverse effects , Radiotherapy Dosage , Radiotherapy Planning, Computer-AssistedABSTRACT
BACKGROUND: Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive treatment which allows delivery of an ablative radiation dose with high accuracy and precision. SABR is an established treatment for both primary and secondary liver malignancies, and technological advances have improved its efficacy and safety. Respiratory motion management to reduce tumour motion and image guidance to achieve targeting accuracy are crucial elements of liver SABR. This phase II multi-institutional TROG 17.03 study, Liver Ablative Radiotherapy using Kilovoltage intrafraction monitoring (LARK), aims to investigate and assess the dosimetric impact of the KIM real-time image guidance technology. KIM utilises standard linear accelerator equipment and therefore has the potential to be a widely available real-time image guidance technology for liver SABR. METHODS: Forty-six patients with either hepatocellular carcinoma or oligometastatic disease to the liver suitable for and treated with SABR using Kilovoltage Intrafraction Monitoring (KIM) guidance will be included in the study. The dosimetric impact will be assessed by quantifying accumulated patient dose distribution with or without the KIM intervention. The patient treatment outcomes of local control, toxicity and quality of life will be measured. DISCUSSION: Liver SABR is a highly effective treatment, but precise dose delivery is challenging due to organ motion. Currently, there is a lack of widely available options for performing real-time tumour localisation to assist with accurate delivery of liver SABR. This study will provide an assessment of the impact of KIM as a potential solution for real-time image guidance in liver SABR. TRIAL REGISTRATION: This trial was registered on December 7th 2016 on ClinicalTrials.gov under the trial-ID NCT02984566 .
Subject(s)
Carcinoma, Hepatocellular/radiotherapy , Liver Neoplasms/radiotherapy , Organ Motion , Radiosurgery/methods , Radiotherapy, Image-Guided/methods , Australia , Carcinoma, Hepatocellular/secondary , Denmark , Fiducial Markers , Humans , Liver Neoplasms/secondary , Quality of Life , Radiosurgery/adverse effects , Radiosurgery/instrumentation , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Image-Guided/adverse effects , Radiotherapy, Intensity-Modulated/methods , Respiration , Treatment OutcomeABSTRACT
OBJECTIVES: The aim of this study was to identify patterns of palliative chemotherapy (CTh) and the associated overall survival (OS) in patients with pancreatic cancer, with specific focus on age. METHODS: Between May 1, 2011, and April 30, 2016, 4260 patients were registered in the Danish Pancreatic Cancer Database. The 1715 patients receiving palliative CTh were retrieved. Age was grouped into less than 70, 70 to less than 75, and 75 years or more. RESULTS: Of the 1715 patients receiving first-line CTh, 586 (34%) underwent second-line CTh and 151 (9%) third-line CTh. First-line gemcitabine resulted in a significant worse survival compared with combination CTh, hazard ratio 1.51. For combination CTh, OS differed between the age groups, P < 0.01. The median OS in the less than 70 years (n = 547), 70 to less than 75 years (n = 163), and 75 years or more (n = 67) groups were 9.3, 9.6, and 7.2 months, respectively. No differences in survival were observed among patients receiving first-line gemcitabine (P = 0.35). CONCLUSIONS: Our findings are useful in treatment-related decision making in patients with pancreatic cancer. A significant survival benefit was observed for all patients after first-line combination CTh. The effect of combination CTh was most prominent among patients aged less than 75 years. By age, no differences in survival were observed in those receiving gemcitabine.
Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Deoxycytidine/analogs & derivatives , Palliative Care/trends , Pancreatic Neoplasms/drug therapy , Practice Patterns, Physicians'/trends , Adult , Age Factors , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Clinical Decision-Making , Databases, Factual , Denmark , Deoxycytidine/adverse effects , Deoxycytidine/therapeutic use , Drug Utilization/trends , Female , Humans , Male , Middle Aged , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/mortality , Registries , Time Factors , Treatment Outcome , GemcitabineABSTRACT
BACKGROUND AND AIMS: Studies suggest that mutations in the CTNNB1 gene are predictive of response to immunotherapy, an emerging therapy for advanced hepatocellular carcinoma (HCC). Analysis of circulating tumor DNA (ctDNA) offers the possibility of serial non-invasive mutational profiling of tumors. Combining tumor tissue and ctDNA analysis may increase the detection rate of mutations. This study aimed to evaluate the frequency of the CTNNB1 p.T41A mutation in ctDNA and tumor samples from HCC patients and to evaluate the concordance rates between plasma and tissue. We further evaluated changes in ctDNA after various HCC treatment modalities and the impact of the CTNNB1 p.T41A mutation on the clinical course of HCC. METHODS: We used droplet digital PCR to analyze plasma from 95 patients and the corresponding tumor samples from 37 patients during 3 years follow up. RESULTS: In tumor tissue samples, the mutation rate was 8.1% (3/37). In ctDNA from HCC patients, the CTNNB1 mutation rate was 9.5% (9/95) in the pre-treatment samples. Adding results from plasma analysis to the subgroup of patients with available tissue samples, the mutation detection rate increased to 13.5% (5/37). There was no difference in overall survival according to CTNNB1 mutational status. Serial testing of ctDNA suggested a possible clonal evolution of HCC or arising multicentric tumors with separate genetic profiles in individual patients. CONCLUSION: Combining analysis of ctDNA and tumor tissue increased the detection rate of CTNNB1 mutation in HCC patients. A liquid biopsy approach may be useful in a tailored therapy of HCC.
Subject(s)
Biomarkers, Tumor , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/diagnosis , Liver Neoplasms/genetics , Mutation , beta Catenin/genetics , Aged , Aged, 80 and over , Alleles , Circulating Tumor DNA , DNA, Neoplasm , Female , Humans , Liquid Biopsy , Male , Middle Aged , Neoplasm Grading , Neoplasm StagingABSTRACT
BACKGROUND AND AIM: Stereotactic ablative body radiotherapy (SABR) is an emerging treatment option in hepatocellular carcinoma (HCC) in patients ineligible for other local ablative therapies. This study reports on the safety and efficacy of SABR in a Danish cohort of HCC patients. MATERIALS AND METHODS: Between January 2009 and December 2018, 28 patients with HCCs were treated with SABR at our institution. The primary endpoint of this retrospective study was local control; secondary endpoints were progression-free survival, overall survival and toxicity. RESULTS: In 28 patients, 32 tumors (median size 3.7 cm, range 1.4-6.8 cm) were treated. The median follow-up time was 16 months. Most patients (68%) received previous liver-directed treatments. A dose of 48 Gy in three or six fractions were given to 43% of the patients. Grad 1 or 2 toxicity was reported in 13 patients (46%), whereas 4 patients (14%) needed hospitalization (grade 3). One-year local control and overall survivals were 90% and 71%, respectively. One-year progression-free survival was 32%, and 65% of patients with disease progression received further HCC therapy. In univariate analysis, none of the examined factors predicted recurrence or overall survival. CONCLUSION: SABR provides high local control to inoperable HCC. SABR can be delivered safely even after previous liver-directed therapies and subsequent therapies are feasible after treatment with SABR. Despite excellent local control, disease progression outside of the irradiated site remains prominent. Further studies are warranted to examine combined therapy approaches to maximize disease control.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Carcinoma, Hepatocellular/radiotherapy , Humans , Morbidity , Neoplasm Recurrence, Local , Retrospective Studies , Treatment OutcomeABSTRACT
Direct-measurement-based methods for assessing workloads of the hand or elbow in the field are rare. Aim of the study was to develop such a method based on the Threshold Limit Value for Hand Activity Level (TLV for HAL). Hence, HAL was quantified using kinematic data (mean power frequencies, angular velocities and micro-pauses) and combined with electromyographic data (root-mean-square values) in order to generate a measurement-based TLV for HAL (mTLV for HAL). The multi-sensor system CUELA including inertial sensors, potentiometers and a 4-channel surface electromyography module was used. For wrist and elbow regions, associations between mTLV for HAL and disorders/complaints (quantified by odds ratios (OR [95%-confidence interval])) were tested exploratively within a cross-sectional field study with 500 participants. Higher workloads were frequently significantly associated with arthrosis of distal joints (9.23 [3.29-25.87]), wrist complaints (2.89 [1.63-5.11]) or elbow complaints (1.99 [1.08-3.67]). The new method could extend previous application possibilities.
Subject(s)
Elbow , Workload , Biomechanical Phenomena , Cross-Sectional Studies , Hand , HumansABSTRACT
BACKGROUND AND AIMS: Plasma circulating tumor DNA (ctDNA) with tumor-specific mutations is an attractive biomarker. The telomerase reverse transcriptase (TERT) C228T promoter mutation is the most prevalent tumor-associated mutation in hepatocellular carcinoma (HCC). We evaluated the presence and prognostic value of the TERT C228T mutation in plasma and tissue in a Danish HCC cohort. METHODS: We analyzed ctDNA from 95 HCC patients and 45 liver cirrhotic patients without HCC for the TERT mutation using droplet digital polymerase chain reaction. We also analyzed DNA from the corresponding primary tumor tissues in 34 HCC patients. RESULTS: The plasma TERT C228T mutation was detected in 42/95 HCC patients (44%) but in none of the non-HCC patients. The TERT mutation was detected in 23/34 tumor samples (68%). The TERT mutation was associated with increased mortality when detected in plasma (adjusted HR 2.16 (1.20-3.88), p = .010) but not in tumor tissue (adjusted HR 1.11 (0.35-3.56), p = .860). There was a positive correlation between the presence of the TERT mutation in plasma and an advanced TNM stage (p < .0001) and vascular invasion (p = .005). Analysis of the TERT mutation in plasma and tumor DNA from the same patient was concordant in 21/34 samples (62%; kappa value 0.31, p = .014). Non-concordance was associated with an early TNM stage. CONCLUSION: The plasma TERT mutation was detected in 44% of HCC patients and in none of non-HCC cirrhotic patients; and was associated with increased mortality. We propose the TERT C228T mutation in ctDNA as a promising HCC biomarker for prognosis.