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- Karimi, Masoud, et al.
(författare)
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A retrospective study of extracolonic, non-endometrial cancer in Swedish Lynch syndrome families
- 2018
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Ingår i: Hereditary Cancer in Clinical Practice. - : BMC. - 1731-2302 .- 1897-4287. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundLynch Syndrome is an autosomal dominant cancer syndrome caused by pathogenic germ-line variants in one of the DNA-mismatch-repair (MMR) genes MLH1, MSH2, MSH6 or PMS2. Carriers are predisposed to colorectal and endometrial cancer, but also other cancer types. The purpose of this retrospective study was to characterize the tumour spectrum of the Swedish Lynch syndrome families.MethodsData were obtained from genetically verified 235 Lynch families from five of the six health care regions in Sweden. The material was stratified for gender, primary cancer, age and mutated gene and the relative proportions of specific cancer types were compared to those in the general population.ResultsA total of 1053 family members had 1493 cancer diagnoses of which 1011 were colorectal or endometrial cancer. Individuals with pathogenic variants in MLH1 and MSH2 comprised 78% of the cohort. Among the 482 non-colorectal/non-endometrial cancer diagnoses, MSH2 carriers demonstrated a significantly increased proportion of urinary tract, gastric, small bowel, ovarian and non-melanoma skin cancer compared to the normal population. MLH1 carriers had an elevated proportion of gastrointestinal cancers (gastric, small bowel, pancreas), while MSH6 carriers had more ovarian cancer than expected. Gastric cancer was predominantly noted in older generations.ConclusionLynch syndrome confers an increased risk for multiple cancers other than colorectal and endometrial cancer. The proportions of other cancers vary between different MMR genes, with highest frequency in MSH2-carriers. Gender and age also affect the tumour spectrum, demonstrating the importance of additional environmental and constitutional parameters in determining the predisposition for different cancer types.
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| 2. |
- Karimi, Masoud, et al.
(författare)
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Associations between Response to Commonly Used Neo-Adjuvant Schedules in Rectal Cancer and Routinely Collected Clinical and Imaging Parameters
- 2022
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 14:24
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Tidskriftsartikel (refereegranskat)abstract
- Complete pathological response (pCR) is achieved in 10–20% of rectal cancers when treated with short-course radiotherapy (scRT) or long-course chemoradiotherapy (CRT) and in 28% with total neoadjuvant therapy (scRT/CRT + CTX). pCR is associated with better outcomes and a “watch-and-wait” strategy (W&W). The aim of this study was to identify baseline clinical or imaging factors predicting pCR. All patients with preoperative treatment and delays to surgery in Uppsala-Dalarna (n = 359) and Stockholm (n = 635) were included. Comparison of pCR versus non-pCR was performed with binary logistic regression models. Receiver operating characteristics (ROC) models for predicting pCR were built using factors with p < 0.10 in multivariate analyses. A pCR was achieved in 12% of the 994 patients (scRT 8% [33/435], CRT 13% [48/358], scRT/CRT + CTX 21% [43/201]). In univariate and multivariate analyses, choice of CRT (OR 2.62; 95%CI 1.34–5.14, scRT reference) or scRT/CRT + CTX (4.70; 2.23–9.93), cT1–2 (3.37; 1.30–8.78; cT4 reference), tumour length ≤ 3.5 cm (2.27; 1.24–4.18), and CEA ≤ 5 µg/L (1.73; 1.04–2.90) demonstrated significant associations with achievement of pCR. Age < 70 years, time from radiotherapy to surgery > 11 weeks, leucocytes ≤ 109/L, and thrombocytes ≤ 4009/L were significant only in univariate analyses. The associations were not fundamentally different between treatments. A model including T-stage, tumour length, CEA, and leucocytes (with scores of 0, 0.5, or 1 for each factor, maximum 4 points) showed an area under the curve (AUC) of 0.66 (95%CI 0.60–0.71) for all patients, and 0.65–0.73 for the three treatments separately. The choice of neoadjuvant treatment in combination with low CEA, short tumour length, low cT-stage, and normal leucocytes provide support in predicting pCR and, thus, could offer guidance for selecting patients for organ preservation.Simple SummaryWe studied real-world patients with locally advanced rectal cancer receiving preoperative radiotherapy with or without chemotherapy. The aim was to find factors associated with complete response to therapy, i.e., no remaining tumour, that could be used to identify patients who would not need surgery in the future. Tumour stage and length, intensity of preoperative treatment, and laboratory factors, such as carcinoembryonic antigen (CEA), leucocyte counts, and platelets, were all associated with complete response. Treatment intensity mattered and when radiotherapy was combined with chemotherapy, 21% had a complete response compared to 8% with radiotherapy alone. A model for identifying patients with a better chance of achieving a complete response was developed using tumour stage and length, CEA, and leukocyte levels as factors predicting complete response.
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| 3. |
- Kettis, Åsa, et al.
(författare)
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Quality of life assessments in clinical practice using either the EORTC-QLQ-C30 or the SEIOQL-DW : a randomized study
- 2021
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Ingår i: Journal of Patient-Reported Outcomes. - : Springer Nature. - 2509-8020. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Effective patient-physician communication can improve patient understanding, agreement on treatment and adherence. This may, in turn, impact on clinical outcomes and patient quality of life (QoL). One way to improve communication is by using patient-reported outcome measures (PROMs). Heretofore, studies of the impact of using PROMs in clinical practice have mostly evaluated the use of standardized PROMs. However, there is reason to believe that individualized instruments may be more appropriate for this purpose. The aim of this study is to compare the effectiveness of the standardized QoL-instrument, the European Organization for Research and Treatment of Cancer Quality of Life C-30 (EORTC-QOL-C30) and the individualized QoL instrument, the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW), in clinical practice.Methods: In a prospective, open-label, controlled intervention study at two hospital out-patient clinics, 390 patients with gastrointestinal cancer were randomly assigned either to complete the EORTC-QOL-C30 or the SEIQoL-DW immediately before the consultation, with their responses being shared with their physician. This was repeated in 3-5 consultations over a period of 4-6 months. The primary outcome measure was patients' health-related QoL, as measured by FACIT-G. Patients' satisfaction with the consultation and survival were secondary outcomes.Results: There was no significant difference between the groups with regard to study outcomes. Neither intervention instrument resulted in any significant changes in health-related QoL, or in any of the secondary outcomes, over time. This may reflect either a genuine lack of effect or sub-optimization of the intervention. Since there was no comparison to standard care an effect in terms of lack of deterioration over time cannot be excluded.Conclusions: Future studies should focus on the implementation process, including the training of physicians to use the instruments and their motivation for doing so. The effects of situational use of standardized or individualized instruments should also be explored. The effectiveness of the different approaches may depend on contextual factors including physician and patient preferences.
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