| 1. |
- Carlsson, Göran, 1951, et al.
(författare)
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A phase I/II study of arfolitixorin and 5-fluorouracil in combination with oxaliplatin (plus or minus bevacizumab) or irinotecan in metastatic colorectal cancer
- 2022
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Ingår i: ESMO Open. - : Elsevier BV. - 2059-7029. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: 5-fluorouracil (5-FU) combined with a folate remains an essential treatment component for metastatic colorectal cancer (mCRC). Leucovorin is the folate most often used, but requires intracellular conversion to a reduced folate, and has high pharmacokinetic variability and limited bioavailability in patients with low folate pathway gene expression. Arfolitixorin is an immediately active form of folate, [6R]-5,10-methylenetetrahydrofolate ([6R]-MTHF), and may improve outcomes.Patients and methods: This open-label, multicenter, phase I/II study in patients with mCRC (NCT02244632) assessed the tolerability and efficacy of first-or second-line arfolitixorin (30, 60, 120, or 240 mg/m2 intravenous) with 5-FU alone, or in combination with oxaliplatin (plus or minus bevacizumab) or irinotecan, every 14 days. Safety, efficacy, and pharmacokinetics were assessed before and after four cycles (8 weeks) of treatment.Results: In 105 treated patients, investigators reported 583 adverse events (AEs) in 86 patients (81.9%), and 256 AEs (43.9%) were potentially related to arfolitixorin and 5-FU. Dose adjustments were required in 16 patients (15.2%). At 8 weeks, 9 out of 57 patients assessed for efficacy achieved an objective response (15.8%), and all 9 achieved a partial response. Six of these nine patients had received arfolitixorin as a first-line treatment. A further 33 patients (57.9%) achieved stable disease. Pharmacokinetics were assessed in 35 patients. The average tmax was 10 min, and area under the plasma concentrationetime curve from time 0 to 1 h increased linearly between 30 and 240 mg/m2. No accumulation was observed for [6R]-MTHF following repeated administration, and there were no major pharmacokinetic differences between cycle 1 and cycle 4 at any dose.Conclusions: Arfolitixorin is a well-tolerated moderator of 5-FU activity. It is suitable for further investigation in mCRC and has the potential to improve treatment outcomes in patients with low folate pathway gene expression. Arfolitixorin can easily be incorporated into current standard of care, requiring minimal changes to chemotherapy regimens.
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| 2. |
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| 3. |
- Danielsson, Helena, et al.
(författare)
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Multimodal mathematical context and video as a tool for teachers´assessment
- 2015
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Konferensbidrag (refereegranskat)abstract
- Multimodal mathematical context And video as a tool for teachers´ assessment Helena Danielsson, PhD, Associate professor Art and media education - hdn@du.se Eva Taflin, PhD, Senior Lecturer Mathematics education - evat@du.seDalarna UniversityThis presentation will discuss some experiences from a four year school research study. The aim of our research was to examine teachers develop when they were part of collaborative discussions based on video recordings and video edited material from specific lessons in their own practice. Our study had two focus; one was to investigate methods and tools that teachers can use to develop their ability in assessment when their students where working with multimodal tasks and the other was to examine how video can be used by teachers wanting to obtain knowledge about assessing.Our study is based on several theories about when teachers collaborate to create new knowledge. The first is the design theoretical approach – where visual ethnography and a semiotic approach contribute to problematize the use and mixture of different modes. A basic assumption of the framework here is that meanings are made and communicated in mathematics through a wide range of semiotic modes. By using video as an essential tool in our research our framework theories concerning visual ethnography, video documentation and individuals as reflective practitioners are also needed.We will choose to highlight some findings that concern the following themes: The use of tasks for assessment, The collaborative talk, The equipment, Ethical dilemmas. Most common was one choice of esthetical mode at a time (combined with written and verbal text), but there were also lessons with mixtures such as stations with different activities. Collaborative talks were evaluated as a meaningful way of sharing knowledge, and the video tool for this, although it raised important ethical discussions. Working with the assessment framework was of great interest to the teachers but it took a lot of time from their ordinary work. In this way the project highlighted more general aspects of school development.The relevance to Nordic educational research also concerns teachers´ use of collaborative talks in assessment work, multimodal tasks in mathematics and video as a research tool in general.
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| 4. |
- Danielsson, Helena, et al.
(författare)
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Multimodal mathematical context and video as a tool for teachers´assessment
- 2014
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Ingår i: Conference proceedings - 4th international Designs for Learning conference 6-9th May 2014.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Project aims and research questionsThis presentation will discuss some experiences from a three year school research study now in its’ final stage. The aim of our research is to examine what kinds of knowledge teachers develop when they are part of collaborative discussions based on video recordings and video edited material from specific lessons in their own practice. Theses specific lessons are designed with multimodal mathematical tasks and students work in a multimodal process. The project has been formulated in close collaboration between teachers, other community representatives and us as researchers. Our study has two focus; one is to investigate methods and tools that teachers can use to develop their ability in assessment when their students are working with multimodal tasks and the other is to examine how video can be used by teachers wanting to obtain knowledge about assessing “creative and aesthetics learning processes” (Skolverket, 2011).The research questions are: How can teachers and pupils assess mathematics abilities shown through creative and esthetic learning processes? How can video be used as a method to contribute to teacher professional development regarding formative and summative assessment? What kind of tools do teachers believe they need in order to assess pupils knowledge in multimodal processes?A part of the study is (together with the teachers) to construct a matrix for assessment of students´ mathematical abilities. The matrices that are created are meant to be adapted to a completed lesson which was characterized by a multimodal task, a task in which not only the spoken or written word is important but also activities and interactions by way of documents, glances and gestures. The multimodal task might accommodate various forms of work – such as laboratory activities with different materials. The matrices that are created within the project framework are planned to be adapted for use by both teachers and students.Theoretical frameworkOur study is based on several theories about when teachers collaborate to create new knowledge (Carlgren 2012). The first is the design theoretical approach – where visual ethnography and a semiotic approach contribute to problematize the use and mixture of different modes. Other theories that are relevant for the study are Jaworskijs (1991) Teaching Triad as developed into inquiry and development of the teachers´ competence, along with Cobbs Design Theory (2000), where the specific mathematics is identified in the school discourse. The design theories expressed in different texts are used, e.g. by Kress & Van Leeuwen (2001); Kress (2010); Selander & Kress (2010), and concerning the discourse work and by Jewitt (2011; 2012) more explicit for the analyze workThe epistemological view we represent is inspired by Vygotsky´s (1978) theory of ZDP and cultural aspects in communication. The study uses sociocultural theory as described by Säljö (2005; 2012). By using multimodal tasks we presume that multimodal tasks contribute toa more qualifiedlearning in which students candevelop theirown explanations, solve problems withdifferentstrategies dispute and present mathematical arguments, discussand comparesolutionspresentedbyvariousforms of representation (Taflin 2007). Previous studies (e.g. Danielsson 2002; Öhman Gullberg 2006; Leijon 2010) have shown that different modalities of “production forms” and media reception may even influence theexperienceofauthenticityand ownershipin a different waythan traditionalschoolwork. A basic assumption of the framework here is therefor that meanings are made and communicated in mathematics through a wide range of semiotic modes (Jewitt 2011; Machin 2011).By using video as an essential tool in our research our framework theories concerning visual ethnography, video documentation and individuals as reflective practitioners are also needed. Appropriate theories are taken from Aull Davies (2008); Pink (2012); Schön (1991); Spencer (2011) and also from Heikkilä & Sahlström (2003).From (audio-)visual cultural theories we are inspired by Wingstedt (2012) who speak ofmultimodalityfor exponential growthofunderstanding.MethodsThe study has been conducted in two steps. First a prestudy over one year, where two primary schools participated (focus on four classes; grade 5 and grade 9). Knowledge gained from the prestudy was used in a more extended study and during the two last years we have had contact with teachers from different schools and levels in four municipalities. With the exception of two researchers we have a group of class teachers from grade 1 to grade 9 participating (about 15 regularly active, while others have been participating at some elected occasions). Two headmasters, two doctorial students and a film maker are also connected to the project. Data collection has been made by both us as researchers, by the teacher themselves and by a professional film maker. In order to learn more about video as a tool we wanted to experiment with different kinds of video equipment in order to examine their functionality for use in a school context. The participating teachers were allowed to use different models but could also choose to use other techniques such as audio recording, photographs, scanning or material copying. Furthermore, they were offered to let students try these it, as part of developing self-assessment and peer assessment. All multimodal tasks in the math lessons were prepared and organized by the teachers themselves. In their second lesson they decided to sometimes try similar ones – in order to develop comparable material, perhaps useful for the matrix discussion. The teachers´ ambition was to design tasks to see if and how they could work to support teachers' assessment of pupils' skills. The researchers empiric data collection, however, both in the prestudy and the second phase of the main study, followed by the same order; Information and presentation sessions in all places and classes. Filming of lessons. After that the film maker edited the material into shorter parts. The edited excerpts were used in a situation of stimulated recall. At this occasion both teachers, colleagues and researchers took part in a video recorded collaborative talk for analysis session (using two cameras). This process was repeated in altogether seven seminars. The video recordings from the seven meetings along with photographs and audio recordings were presented later on at a summing up meeting, where all the main participants took part.We are currently in the process of preparing survey questions, addressed to the teachers, for the final data collection. Some findingsAs the final results not yet complete, we have chosen to highlight some findings that we consider of interest to discuss and reflections upon. They concern the following themes: The framework for assessment, Editing concerns, The equipment, ethical dilemmas.Framework for assessment: Quite early in the project the teachers at one of the schools made a framework (matrix) in order to test it for assessment in maths – and made it available for use by other teachers in the project (that meant that four different municipalities were able to test it). These frameworks were made from the point of view that the multimodal tasks were designed as a “creative and esthetical learning process”. Interesting here was that the teachers also active in the first grades in school also tried parts of this advanced models. In the project matrices constructed for art education also played a role in maths.Editing concerns: The edited video material was critical in the analyse process. Through the edited film teachers were reminded about moments in the lesson – they saw or heard details that could give a more complete picture of the lesson.The equipment: The qualities of video cameras of different sizes were discussed a lot. One finding was that sound was sometimes more important than the pictures. In some classes the teachers preferred to use only sound recording in order to be more discrete. In other classes mainly stills were used and copies made of pupils work.Ethical dilemmas: The use of video recording, stills or sound material raised unexpected ethical issues. In some schools there were immigrant children with protected identities. Other classes contained students with neurological diagnoses. The parents of these children were hesitant to letting their children be filmed. How could we as researchers handle this? The ethic council at our university expressed doubts about the use of video at all while observing children in a school context. Is this attitude similar in other countries, other university councils? We live in a society where the use and presence of digital resources is increasing, but authorities views here might raise limitations to the use of video as a visual research method. The task, in our opinion, must be to learn how to handle this, not to avoid it. Our studies give an insight into information that can be used to increase this ability.In summary all the teachers formulated their personal designed tasks in order to test different modes. Most common was one choice of esthetical mode at a time (combined with written and verbal text), but there were also lessons with mixtures such as stations with different activities. Teachers commented that the reflection time at the end of lessons became of great importance to sum up questions around the pupils individual learning processes - something they partly developed and stressed more after watching the film excerpts.Working with the assessment framework was of great interest to the teachers but it took a lot of time from their ordinary work, and in some cases the teachers received no support from their headmaster. In this way the project highlighted more general aspects of school development.
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| 5. |
- Danielsson, Helena, et al.
(författare)
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Rapport från projektet Multimodala uppgifter och bedömning i matematik : Video och kollaborativa samtal som metod vid lärares bedömning av elevers matematiska kunskaper
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This research will discuss some experiences from a four year school research study. It was conducted in cooperation with teachers from four municipalities in Dalarna. The aim of the research was to examine teachers´ professional development when they participated in collaborative discussions based on video recordings and video edited material from specific lessons in their own practice. The study had two foci one was to investigate methods and tools that teachers can use to develop their ability to assess their students while working on multimodal tasks. The other was to examine how video can be used by teachers wanting to obtain knowledge about assessing students. The study is based on several theories about when teachers collaborate to create new knowledge. The first is the design theoretical approach – where visual ethnography and a semiotic approach contribute to problematize the use and mixture of different modes. A basic assumption of the framework here is that meanings are made and communicated in mathematics through a wide range of semiotic modes. By using video as an essential tool in the research the framework theories concerning visual ethnography, video documentation and individuals as reflective practitioners were also needed. The findings can be divided into the following themes: the use of tasks for assessment, collaborative discussion, equipment, ethical dilemmas. Collaborative discussions were evaluated as a meaningful way of sharing knowledge. The use of video recordings in association with these discussions raised important ethical issues. Working with the assessment framework was of great interest to the teachers but it took a lot of time from their ordinary work. In this way the project highlighted more general aspects of school development. The research also concerns teachers´ use of collaborative discussions in assessment work, multimodal tasks in mathematics and video as a research tool in general.
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| 6. |
- Derwinger, Kristoffer, 1969, et al.
(författare)
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Tumour differentiation grade is associated with TNM staging and the risk of node metastasis in colorectal cancer.
- 2010
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Ingår i: Acta oncologica. - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 49:1, s. 57-62
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The tumour differentiation grade has been shown by numerous multivariate analyses to be a stage-independent prognostic factor in colorectal cancer. The aim of this study was to explore the importance of differentiation grading for the staging of colorectal cancer and how it relates to the components of the TNM system. MATERIAL AND METHODS: The study was a retrospective single-centre analysis of all patients undergoing surgical resection for colorectal cancer during the period 2002-2007 (n = 1239). The clinical parameters and pathology data of overall stage, differentiation grade, local tumour (T)-stage and metastasis status (M-stage) were included as well as the lymph node count of both assessed and metastatic nodes. The differentiation grade was correlated with demography, overall stage and each component of the TNM staging system. The correlation between differentiation grade and N-stage was also explored for the separate T-stages. RESULTS: The tumour differentiation grade correlated significantly with the overall TNM stage (p < 0.0001). The grade significantly correlated with the T-stage and the risk of having lymph node metastasis (p < 0.0001). A high grade was associated with a higher positive lymph node count in stage III disease (p < 0.0002). For the T-stages, the risk of node metastasis was significantly linked to the tumour grade. A low grade (G1) T2 had a 17% risk of lymph node metastasis compared to a 44% risk for a high grade (G4) T2. CONCLUSION: Tumour differentiation is an important prognostic factor. It correlates significantly with the overall stage of the TNM system and also to each of its components. The risk of having lymph node metastasis for each T-stage also correlates with the tumour grade. The findings can be of importance in postoperative risk assessment or when considering local resection procedures like TEM.
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| 7. |
- Emland, Frans, et al.
(författare)
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Prolonged postoperative length of stay may be a valuable marker for susceptibility to relapse beyond established risk factors in patients with stage III colon cancer
- 2022
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Ingår i: World Journal of Surgical Oncology. - : Springer Science and Business Media LLC. - 1477-7819. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Delay from surgery to adjuvant chemotherapy causes impaired survival among patients undergoing radical resection for stage III colon cancer, and the underlying mechanism for this is incompletely clarified. It is established that prolonged postoperative hospital length of stay (LOS) is associated with delayed initiation of the adjuvant treatment driving the assumption that prolonged LOS is prognostically unfavorable due to this fact and case mix factors. We hypothesize that prolonged LOS after surgery is a valuable marker for susceptibility to relapse that is not detected in established prognostic factors and, alone, associated with a shorter disease-free survival (DFS). Materials and methods: A total of 690 consecutive patients undergoing elective radical resection for stage III colon cancer in 2000–2015 were identified in a prospective detailed facility database. Univariate and multivariate analyses were performed using Cox proportional hazards model in the evaluation of LOS as an independent prognostic factor. Results: Short postoperative LOS, low comorbidity, and few complications were associated with longer DFS (p < 0.01). Fewer patients in the short and intermediate LOS groups had a relapse in their disease (28% and 33%, respectively), compared to the patients with longer LOS (40%, p < 0.05). LOS was a prognostic factor for DFS in the unadjusted univariate model (HR 1.04 per unit change) and remained statistically significant in the adjusted multivariate analysis, with a HR of 1.03 per hospital day (p < 0.01). Conclusions: Postoperative LOS independently correlates with the risk of recurrence and DFS, regardless of if adjuvant chemotherapy is given, along with the factors such as age, comorbidity, complications, and tumor features. We propose a further investigation into the causal mechanisms based on tumor and host biology linking LOS to DFS beyond established risk factors.
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| 8. |
- Engstrand, J., et al.
(författare)
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Liver resection and ablation for squamous cell carcinoma liver metastases
- 2021
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Ingår i: BJS Open. - Oxford, United Kingdom : Oxford University Press. - 2474-9842. ; 5:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Limited evidence exists to guide the management of patients with liver metastases from squamous cell carcinoma (SCC). The aim of this retrospective multicentre cohort study was to describe patterns of disease recurrence after liver resection/ablation for SCC liver metastases and factors associated with recurrence-free survival (RFS) and overall survival (OS).METHOD: Members of the European-African Hepato-Pancreato-Biliary Association were invited to include all consecutive patients undergoing liver resection/ablation for SCC liver metastases between 2002 and 2019. Patient, tumour and perioperative characteristics were analysed with regard to RFS and OS.RESULTS: Among the 102 patients included from 24 European centres, 56 patients had anal cancer, and 46 patients had SCC from other origin. RFS in patients with anal cancer and non-anal cancer was 16 and 9 months, respectively (P = 0.134). A positive resection margin significantly influenced RFS for both anal cancer and non-anal cancer liver metastases (hazard ratio 6.82, 95 per cent c.i. 2.40 to 19.35, for the entire cohort). Median survival duration and 5-year OS rate among patients with anal cancer and non-anal cancer were 50 months and 45 per cent and 21 months and 25 per cent, respectively. For the entire cohort, only non-radical resection was associated with worse overall survival (hazard ratio 3.21, 95 per cent c.i. 1.24 to 8.30).CONCLUSION: Liver resection/ablation of liver metastases from SCC can result in long-term survival. Survival was superior in treated patients with liver metastases from anal versus non-anal cancer. A negative resection margin is paramount for acceptable outcome.
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| 9. |
- Engstrand, J., et al.
(författare)
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The Resection Rate of Synchronously Detected Liver and Lung Metastasis from Colorectal Cancer Is Low-A National Registry-Based Study
- 2023
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 15:5
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Real-life data on the occurrence and treatment of synchronously detected liver and lung metastases from colorectal cancer are lacking. Through the merging of several Swedish nationwide patient quality registries, we aimed to answer these questions. We found that synchronous liver and lung colorectal metastases are rare and that a minority undergo resection of both metastatic sites, but if they do, they have an excellent survival. It is likely that a larger proportion of patients could be offered treatment that leads to a prolonged overall survival. We also found differences in regional treatment approaches across Sweden, but the reasons for this are unknown, which warrants further studies. Population-based data on the incidence and surgical treatment of patients with colorectal cancer (CRC) and synchronous liver and lung metastases are lacking as are real-life data on the frequency of metastasectomy for both sites and outcomes in this setting. This is a nationwide population-based study of all patients having liver and lung metastases diagnosed within 6 months of CRC between 2008 and 2016 in Sweden identified through the merging of data from the National Quality Registries on CRC, liver and thoracic surgery and the National Patient Registry. Among 60,734 patients diagnosed with CRC, 1923 (3.2%) had synchronous liver and lung metastases, of which 44 patients had complete metastasectomy. Surgery of liver and lung metastases yielded a 5-year OS of 74% (95% CI 57-85%) compared to 29% (95% CI 19-40%) if liver metastases were resected but not the lung metastases and 2.6% (95% CI 1.5-4%) if non-resected, p < 0.001. Complete resection rates ranged from 0.7% to 3.8% between the six healthcare regions of Sweden, p = 0.007. Synchronous liver and lung CRC metastases are rare, and a minority undergo the resection of both metastatic sites but with excellent survival. The reasons for differences in regional treatment approaches and the potential of increased resection rates should be studied further.
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| 10. |
- Liang, Frank, et al.
(författare)
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A Fraction of CD8+T Cells from Colorectal Liver Metastases Preferentially Repopulate Autologous Patient-Derived Xenograft Tumors as Tissue-Resident Memory T Cells
- 2022
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:12
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Treatment options for colorectal cancer (CRC) patients with liver metastases are often limited to liver surgery with or without chemotherapy. However, not all patients present operable colorectal liver metastases (CRLMs). Thus, alternative therapies that exploit the anti-tumor potential of tumor-infiltrating lymphocytes (TILs) are being evaluated. The establishment of markers connecting the phenotype to the function of tumor-reactive CD8+ TILs could aid diagnostic and therapeutic advances. In this regard, tissue-resident memory T cells (T-RM cells) could be a potential candidate for therapies targeting TILs. Putative tumor-reactive T-RM cells among CD8+ TILs likely co-express CD103 and CD39, since these markers indicate stable tumor residency and repeated response to antigens from the tumor environment, respectively. Our phenotypic and functional analyses of TILs in CRLM, with a specific focus on CD103+CD8+ T-RM cells, may guide the improvement of TIL-mediated CRC treatments. The diversity of T cells in the human liver may reflect the composition of TILs in CRLM. Our ex vivo characterization of CRLM vs. adjacent liver tissue detected CD103+CD39+CD8+ T-RM cells predominantly in CRLM, which prompted further assessments. These T-RM cells responded to cognate antigens in vitro. As functional activities of autologous TILs are central to the implementation of personalized cancer treatments, we applied a patient-derived xenograft (PDX) model to monitor TILs' capacity to control CRLM-derived tumors in vivo. We established PDX mice with CRLMs from two patients, and in vitro expansion of their respective TILs resulted in opposing CD4+ vs. CD8+ TIL ratios. These CRLMs also displayed mutated KRAS, which enabled trametinib-mediated inhibition of MEK. Regardless of the TIL subset ratio, persistent or transient control of CRLM-derived tumors of limited size by the transferred TILs was observed only after trametinib treatment. Of note, a portion of transferred TILs was observed as CD103+CD8+ T-RM cells that strictly accumulated within the autologous CRLM-derived tumor rather than in the spleen or blood. Thus, the predominance of CD103+CD39+CD8+ T-RM cells in CRLM relative to the adjacent liver and the propensity of CD103+CD8+ T-RM cells to repopulate the autologous tumor may identify these TILs as strategic targets for therapies against advanced CRC.
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