| 1. |
- Almlöv, Karin, et al.
(författare)
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MRI Lymph Node Evaluation for Prediction of Metastases in Rectal Cancer
- 2020
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 40:5, s. 2757-2763
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To explore whether the size and characteristics of the largest regional lymph node in patients with rectal cancer, based on magnetic resonance imaging (MRI), following neoadjuvant therapy and before surgery, is able to identify patients at high risk of developing metachronous metastases.Patients and Methods: A retrospective case–control study with data from the Swedish Colo-Rectal Cancer Registry. Forty patients were identified with metachronous metastases (M+), and 40 patients without metastases (M0) were matched as controls.Results: Patients with M+ disease were more likely to have a regional lymph node measuring ≥5 mm than patients with M0. (87% vs. 65%, p=0.02). There was also a significant difference between the groups regarding the presence of an irregular border of the largest lymph node (68% vs. 40%, p=0.01).Conclusion: Lymph nodes measuring ≥5 mm with/without displaying irregular borders at MRI performed after neoadjuvant therapy emerged as risk factors for metachronous metastases in patients with rectal cancer. Intensified follow-up programmes may be indicated in these patients.
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| 2. |
- Björnsson, Bergthor, et al.
(författare)
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Digital twins to personalize medicine
- 2020
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Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 12:1
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Forskningsöversikt (refereegranskat)abstract
- Personalized medicine requires the integration and processing of vast amounts of data. Here, we propose a solution to this challenge that is based on constructing Digital Twins. These are high-resolution models of individual patients that are computationally treated with thousands of drugs to find the drug that is optimal for the patient.
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| 3. |
- Blomstrand, Hakon, et al.
(författare)
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Real-world evidence on first- and second-line palliative chemotherapy in advanced pancreatic cancer
- 2021
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Ingår i: World Journal of Clinical Oncology. - : Baishideng Publishing Group Inc. - 2218-4333. ; 12:9, s. 787-799
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Forskningsöversikt (refereegranskat)abstract
- In spite of recent diagnostic and therapeutic advances, the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains very poor. As most patients are not amenable to curative intent treatments, optimized palliative management is highly needed. One key question is to what extent promising results produced by randomized controlled trials (RCTs) correspond to clinically meaningful outcomes in patients treated outside the strict frames of a clinical trial. To answer such questions, real-world evidence is necessary. The present paper reviews and discusses the current literature on first- and second-line palliative chemotherapy in PDAC. Notably, a growing number of studies report that the outcomes of the two predominant first-line multidrug regimens, i.e. gemcitabine plus nab-paclitaxel (GnP) and folfirinox (FFX), is similar in RCTs and real-life populations. Outcomes of second-line therapy following failure of first-line regimens are still dismal, and considerable uncertainty of the optimal management remains. Additional RCTs and real-world evidence studies focusing on the optimal treatment sequence, such as FFX followed by GnP or vice versa, are urgently needed. Finally, the review highlights the need for prognostic and predictive biomarkers to inform clinical decision making and enable personalized management in advanced PDAC.
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| 4. |
- Elander, Nils, 1980-, et al.
(författare)
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Genetic deletion of mPGES-1 accelerates intestinal tumorigenesis in APCMin/+ mice
- 2008
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 372:1, s. 249-253
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Tidskriftsartikel (refereegranskat)abstract
- The induced synthesis of bioactive prostanoids downstream of cyclooxygenase-2 (COX-2) and prostaglandin H2 (PGH2) exerts a critical event in colorectal carcinogenesis. Here we demonstrate that APCMin/+ mice with genetic deletion of microsomal prostaglandin E synthase-1 (mPGES-1), which catalyses the terminal conversion of PGH2 into PGE2, surprisingly develop more and generally larger intestinal tumors than do mPGES-1 wild type littermates (mean number of tumors/intestine 80 vs. 38, p < 0.0005, mean tumor diameter 1.64 vs. 1.12 mm, p < 0.0005). No deviation regarding the expression of other PGE2 related enzymes (COX-1, COX-2, mPGES-2, cPGES, and 15-PGDH) or receptors (EP1-4) was obvious among the mPGES-1 deficient mice. PGE2 levels were suppressed in tumors of mPGES-1 deficient animals, but the concentrations of other PGH2 derived prostanoids were generally enhanced, being most prominent for TxA2 and PGD2. Thus, we hypothesise that a redirected synthesis towards other lipid mediators might (over)compensate for loss of mPGES-1/PGE2 during intestinal tumorigenesis. Nevertheless, our results question the suitability for mPGES-1 targeting therapy in the treatment or prevention of colorectal cancer. © 2008 Elsevier Inc. All rights reserved.
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| 5. |
- Elander, Nils, 1980-, et al.
(författare)
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Matrix metalloproteinase (MMP) -1, -2, -3 and -9 promoter polymorphisms in colorectal cancer
- 2006
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Ingår i: Anticancer Research. - : International Institute of Anticancer Research. - 0250-7005 .- 1791-7530. ; 26:1B, s. 791-795
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Tidskriftsartikel (refereegranskat)abstract
- Background: Matrix metalloproteinases (MMPs) are a group of matrix-degrading proteins implicated in several pathological processes, e.g., invasion and metastasis in malignant diseases such as colorectal cancer (CRC). Materials and methods: One hundred and twenty-seven CRC patients and 208 controls were genotyped for MMP-1, -2, -3 and -9 promoter polymorphisms. The genotyping was performed with PCR/primer-extension/DHPLC or PCR/RFLP. Results: The MMP-1 2G allele was significantly associated with CRC (p=0.037). No significant association between CRC and MMP-2, -3 or -9 polymorphisms was evident. The analysis of polymorphisms in the clinicopathological subgroups displayed no significant associations. Conclusion: The MMP-1 promoter polymorphism seems to affect the susceptibility to CRC, while MMP-2, -3 and -9 polymorphisms appear less likely to have any impact on CRC.
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| 6. |
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| 7. |
- Ellegård, Sander, et al.
(författare)
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ERBB2 and PTPN2 gene copy numbers as prognostic factors in HER2-positive metastatic breast cancer treated with trastuzumab
- 2019
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Ingår i: Oncology Letters. - Athens, Greece : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 17:3, s. 3371-3381
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Tidskriftsartikel (refereegranskat)abstract
- Trastuzumab has markedly improved the treatment and long-term prognosis of patients with HER2-positive breast cancer. A frequent clinical challenge in patients with relapsing and/or metastatic disease is de novo or acquired trastuzumab resistance, and to date no predictive biomarkers for palliative trastuzumab have been established. In the present study, the prognostic values of factors involved in the HER2-associated PI3K/Akt signalling pathway were explored. The first 46 consecutive patients treated at the Department of Oncology, Linkoping University Hospital between 2000 and 2007 with trastuzumab for HER2-positive metastatic breast cancer were retrospectively included. The gene copy number variation and protein expression of several components of the PI3K/Akt pathway were assessed in the tumour tissue and biopsy samples using droplet digital polymerase chain reaction and immunohistochemistry. Patients with tumours displaying a high-grade ERBB2 (HER2) amplification level of amp;gt;= 6 copies had a significantly improved overall survival hazard ratio [(HR)=0.4; 95%, confidence interval (CI): 0.2-0.9] and progression-free survival (HR=0.3; 95% CI: 0.1-0.7) compared with patients with tumours harbouring fewer ERBB2 copies. High-grade ERBB2 amplification was significantly associated with the development of central nervous system metastases during palliative treatment. Copy gain (amp;gt;= 3 copies) of the gene encoding the tyrosine phosphatase PTPN2 was associated with a shorter overall survival (HR=2.0; 95% CI: 1.0-4.0) and shorter progression-free survival (HR=2.1; 95% CI: 1.0-4.1). In conclusion, high ERBB2 amplification level is a potential positive prognostic factor in trastuzumab-treated HER2-positive metastatic breast cancer, whereas PTPN2 gain is a potential negative prognostic factor. Further studies are warranted on the role of PTPN2 in HER2 signalling.
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| 8. |
- Ellegård, Sander, 1985-
(författare)
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HER2-positive breast cancer : Clinical and molecular aspects
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundHuman Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer is notable for its aggressive behavior, however with the introduction of trastuzumab in the early 2000’s, prognosis has improved. This thesis investigates the efficacy of trastuzumab in real-world settings after its introduction and evaluates the prognostic value of molecular biomarkers, aiming to optimize treatment approaches and improve patient outcomes.Material and MethodsHER2-positive patients treated in the advanced and early stages of breast cancer were retrospectively identified using Swedish patient registries and through the review of medical records.Study I included 46 patients with advanced breast cancer treated with trastuzumab between 2000 and 2007. Immunohistochemical analysis of several proteins hypothesized to be involved in trastuzumab resistance were evaluated. Additionally, gene copy number variations were analyzed using droplet digital PCR.Study II include 599 patients who received adjuvant trastuzumab between 2006 and 2014 in the Southeastern health care region, in order to evaluate the implementation of trastuzumab after its approval and to evaluate patient outcomes with regard to clinicopathological variables.Study III conducted quantitative analyses of stromal tumor-infiltrating lymphocytes (sTILs) in patients with available tumor material from the same cohort identified in study II. Additionally, a case-control study of 21 cases with 21 matched controls treated with trastuzumab were analyzed with RNA-sequencing in order to identify important differentially expressed genes.ResultsStudy I demonstrated that trastuzumab treatment in a real-world setting had similar survival as in pivotal clinical trials. Additionally, high amplification of HER2 correlated with improved progression-free survival (PFS) and overall survival (OS) in advanced breast cancer patients and PTPN2 gain was correlated with reduced PFS and OS.Study II confirmed trastuzumab's efficacy in a large real-world cohort. Trastuzumab treatment, estrogen receptor (ER) status and number of metastatic lymph nodes were the most important prognostic factors for breast cancer-specific survival and distant recurrence-free survival.Study III identified a significant association between high levels of sTILs and improved overall survival. Additionally, several G-protein coupled receptors (GPCRs) involved in EGFR and Wnt signaling were found to be upregulated in cases vs controls.ConclusionsTrastuzumab maintains its efficacy in clinical practice, affirming its role in current treatment regimens for HER2-positive breast cancer. The findings support the prognostic significance of sTILs and suggest HER2-amplification levels as a relevant prognostic factor. We propose PTPN2 and several GPCRs as areas for future research.
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| 9. |
- Wallander, Mikael, et al.
(författare)
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Real world aspects of palliative trifluridine plus tiperacil (TAS-102) in refractory metastatic colorectal cancer
- 2020
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Ingår i: Journal of Gastrointestinal Oncology. - : AME Publishing Company. - 2078-6891 .- 2219-679X. ; 11:4, s. 616-625
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Tidskriftsartikel (refereegranskat)abstract
- Background: While recent randomised phase III trials show that trifluridine/tiperacil (TAS-102) may prolong life in patients with refractory metastatic colorectal cancer (rmCRC), palliative aspects on its efficacy and tolerability in real world patients need further elucidation. Methods: A retrospective observational multicentre study was designed, including all patients with rmCRC who received TAS-102 under 2016-2019 in the South East Health Care region of Sweden. 48 patients were identified. Primary outcome was overall survival (OS) and secondary outcomes were progression-free survival (PFS), time to ECOG performance status deterioration (PSD), safety and dose reductions, admission to and duration of access to palliative care, and administration of TAS-102 in the last 30 days before death. Results: Median OS, PFS, and time to PSD (a proxy for impaired quality of life) from start of TAS-102 were 6.4 months (95% CI: 4.4-8.4), 2.3 months (95% CI: 1.8-2.7) and 2.5 months (95% CI: 1.9-3.2), respectively. Following uni- and multivariable regression analyses, the number of previous treatment lines (<= 2 vs. >= 3) was statistically independent for OS (median 7.8 vs. 5.3 months, P=0.05), PFS (median 2.4 vs. 1.8 months, P=0.03), and time to PSD (median 2.8 vs. 1.8 months, P=0.03). Thirty-four (71%) of the patients received reduced doses. The most common grade 3-4 toxicity was neutropenia (39%). Forty-three (90%) were admitted to GP or hospital-based home palliative care. Median time for access to any form of palliative care before death was 2.3 (95% CI: 0.5-3.2) months. Few patients (n=3, 7%) received their last dose of TAS-102 in their last 30 days of life. Conclusions: The outcome and tolerability of TAS-102 in rmCRC appear similar in a real-world context and randomised trials. The retrospective design and limited sample size preclude firm conclusions on subgroup analyses, but it appears that the prognosis is slightly better the earlier TAS-102 is introduced. Treatment durations are generally short, and early admission to a palliative care provider is recommended.
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| 10. |
- Wode, Kathrin, et al.
(författare)
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Efficacy of mistletoe extract as a complement to standard treatment in advanced pancreatic cancer : study protocol for a multicentre, parallel group, double-blind, randomised, placebo-controlled clinical trial (MISTRAL)
- 2020
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Ingår i: Trials. - : BioMed Central. - 1745-6215. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Most pancreatic cancer patients present with advanced stage at diagnosis with extremely short expected survival and few treatment options. A multimodal palliative approach is necessary for symptom relief and optimisation of health-related quality of life. In a recent open-label trial of mistletoe extract for advanced pancreatic cancer patients not eligible for chemotherapy, promising results on improved overall survival and better health-related quality of life were reported.The objective of the present study is to assess the value of mistletoe extract as a complement to standard treatment (palliative chemotherapy or best supportive care) in advanced pancreatic cancer patients with regard to overall survival and health-related quality of life.Methods: The trial is prospective, randomised, double-blind, multicentre, parallel group and placebo-controlled. In total, 290 participants are randomly assigned to placebo or mistletoe extract given subcutaneously in increasing dosage from 0.01 to 20 mg three times per week for 9 months. Stratification is performed for site and palliative chemotherapy. Main inclusion criteria are advanced pancreatic cancer and Eastern Cooperative Oncology Group performance status 0 to 2; main exclusion criteria are life expectancy less than 4 weeks and neuroendocrine tumour of the pancreas. Two ancillary studies on sub-sets of participants are nested in the trial: a biomarker study collecting blood samples and a cross-sectional qualitative study with semi-structured face-to-face interviews.Discussion: To our knowledge, this is the first placebo-controlled randomised trial assessing the impact of mistletoe extract as a complement to standard treatment on overall survival and health-related quality of life in patients with advanced pancreatic cancer. The presented trial with its two nested ancillary studies exploring biomarkers and patient experiences is expected to give new insights into the treatment of advanced pancreatic cancer.
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