| 1. |
- Glimelius, Bengt, et al.
(författare)
-
U-CAN : a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.
- 2018
-
Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 57:2, s. 187-194
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.
|
|
| 2. |
|
|
| 3. |
- Enblad, Malin, et al.
(författare)
-
Signet Ring Cell Colorectal and Appendiceal Cancer : A Small Signet Ring Cell Component Is Also Associated with Poor Outcome
- 2023
-
Ingår i: Cancers. - : MDPI. - 2072-6694. ; 15:9
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Colorectal signet ring cell (SRC) carcinoma with ≥50% SRCs (SRC ≥ 50) has a poor prognosis, but the prognostic role of SRCs < 50% (SRC < 50) is unclear. The aim of this study was to provide a clinicopathological characterization of SRC colorectal and appendiceal tumours and analyse the importance of the SRC component size.Methods: All patients in the Swedish Colorectal Cancer Registry diagnosed with colorectal or appendiceal cancer in 2009–2020 at Uppsala University Hospital, Sweden, were included. The SRCs were verified, and the components estimated by a gastrointestinal pathologist.Results: Of the 2229 colorectal cancers, 51 (2.3%) had SRCs, with a median component size of 30% (interquartile range of 12.5–40) and 10 (0.45%) had SRC ≥ 50. The SRC tumours were primarily localized in the right colon (59%) and appendix (16%). No patients with SRCs had stage I disease, and 26 (51%) had stage IV, of whom, 18 (69%) had peritoneal metastases. The SRC tumours were often high grade with perineural and vascular invasion. The 5-year overall survival (OS) rate for patients with SRC ≥ 50 were 20% (95% confidence interval (CI) 6–70), for SRC < 50, 39% (95% CI 24–61); and for non-SRCs, 55% (95% CI 55–60). Among the patients with SRC < 50 and <50% extracellular mucin, the 5-year OS was 34% (95% CI 19–61), while those with ≥50% extracellular mucin had an OS of 50% (95% CI 25–99). The 5-year recurrence-free survival rates were 51% (95% CI 13–83) for patients with SRC tumours, as compared to 83% (95% CI 77–89) and 81% (95% CI 79–84) for mucinous and non-mucinous adenocarcinoma, respectively.Conclusions: The presence of SRCs was strongly associated with aggressive clinicopathological features, peritoneal metastases, and poor prognosis, also when they make up <50% of a tumour.Simple SummarySignet ring cell (SRC) carcinoma of colorectal and appendiceal cancer is rare but is recognized as the histopathological subtype with the poorest prognosis. However, the prognostic relevance of a SRC component <50% is unclear. The aim of this study was to provide a clinicopathological characterization of all SRC-containing colorectal and appendiceal cancers, including those with <50% SRCs. The results showed that SRCs, both ≥50% and <50%, were associated with aggressive histopathological features, advanced stages, and, particularly, peritoneal metastases. Information about the presence of SRCs in tumour tissue, not only in the case of ≥50% SRCs, should be routinely registered in pathology reports and clinical registers to enable larger studies that can aid our understanding of SRCs in colorectal and appendiceal cancers.
|
|
| 4. |
- Hammarström, Klara, et al.
(författare)
-
A Comprehensive Evaluation of Associations Between Routinely Collected Staging Information and The Response to (Chemo)Radiotherapy in Rectal Cancer
- 2021
-
Ingår i: Cancers. - : MDPI. - 2072-6694. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Rectal cancer patients are often treated with radiotherapy, either alone or combined with chemotherapy, prior to surgery to enable radical surgery on a non-resectable tumor or to lower the recurrence risk. For some patients, the tumor disappears completely after preoperative treatment, while others experience little or no benefit. Accurate prediction of therapy response before treatment is of great importance for a personalized treatment approach and intentional organ preservation. We performed a comprehensive evaluation of the predictive capacity of all routinely collected staging information at diagnosis in a population-based, completely staged patient material of 383 patients representing a real-life clinical situation. Size or stage of the rectal tumor were independent predictors of excellent response irrespective of preoperative treatment, with small/early-stage tumors being significantly more likely to reach a complete response. Levels of the tumor marker carcinoembryonic antigen (CEA) above upper normal limit halved the chance of response. Radiotherapy (RT) or chemoradiotherapy (CRT) are frequently used in rectal cancer, sometimes resulting in complete tumor remission (CR). The predictive capacity of all clinical factors, laboratory values and magnetic resonance imaging parameters performed in routine staging was evaluated to understand what determines an excellent response to RT/CRT. A population-based cohort of 383 patients treated with short-course RT (5 x 5 Gy in one week, scRT), CRT, or scRT with chemotherapy (scRT+CT) and having either had a delay to surgery or been entered into a watch-and-wait program were included. Complete staging according to guidelines was performed and associations between investigated variables and CR rates were analyzed in univariate and multivariate analyses. In total, 17% achieved pathological or clinical CR, more often after scRT+CT and CRT than after scRT (27%, 18% and 8%, respectively, p < 0.001). Factors independently associated with CR included clinical tumor stage, small tumor size (<3 cm), tumor level, and low CEA-value (<3.8 mu g/L). Size or stage of the rectal tumor were associated with excellent response in all therapy groups, with small or early stage tumors being significantly more likely to reach CR (p = 0.01 (scRT), p = 0.01 (CRT) and p = 0.02 (scRT+CT). Elevated level of carcinoembryonic antigen (CEA) halved the chance of response. Extramural vascular invasion (EMVI) and mucinous character may indicate less response to RT alone.
|
|
| 5. |
|
|
| 6. |
- Hammarström, Klara, et al.
(författare)
-
Determining the use of preoperative (chemo)radiotherapy in primary rectal cancer according to national and international guidelines
- 2019
-
Ingår i: Radiotherapy and Oncology. - : ELSEVIER IRELAND LTD. - 0167-8140 .- 1879-0887. ; 136, s. 106-112
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Pre-operative radiotherapy (RT) or chemoradiotherapy (CRT) is frequently used prior to rectal cancer surgery to improve local control and survival. The treatment is administered according to guidelines, but these recommendations vary significantly between countries. Based on the stage distribution and risk factors of rectal cancers as determined by magnetic resonance imaging (MRI) in an unselected Swedish population, the use of RT/CRT according to 15 selected guidelines is described. Materials and methods: Selected guidelines from different countries and regions were applied to a wellcharacterized unselected population-based material of 686 primary non-metastatic rectal cancers staged by MRI. The fraction of patients assigned to surgery alone or surgery following pre-treatment with (C) RT was determined according to the respective guideline. RT/CRT administered to rectal cancer patients for other reasons, for example, for organ preservation or palliation, was not considered. Results: The fraction of patients with a clear recommendation for pre-treatment with (C) RT varied between 38% and 77% according to the different guidelines. In most guidelines, CRT was recommended to all patients who were not operated directly, and, in others, short-course RT was also recommended to patients with intermediate risk tumours. If only non-resectable or difficult to resect tumours were recommended pre-treatment, as stated in many Japanese publications, 9% would receive CRT followed by a delay to surgery. Conclusions: According to most guidelines, well over 50% of primary non-metastatic rectal cancer patients from a general population, in which screening for colorectal cancer is not practised, are recommended treatment with pre-operative/neo-adjuvant therapy. (C) 2019 Elsevier B. V. All rights reserved. Radiotherapy and Oncology
|
|
| 7. |
- Hammarström, Klara, et al.
(författare)
-
Stage distribution utilizing magnetic resonance imaging in an unselected population of primary rectal cancers
- 2018
-
Ingår i: European Journal of Surgical Oncology. - : ELSEVIER SCI LTD. - 0748-7983 .- 1532-2157. ; 44:12, s. 1858-1864
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Pre-operative radiotherapy (RT) or chemo-radiotherapy (CRT) are sometimes recommended prior to rectal cancer surgery, but guideline recommendations vary. The aim was to describe stage distribution and other important characteristics required for the treatment decision of patients with primary rectal cancers utilizing magnetic resonance imaging (MRI) in an unselected population. Patients and methods: All 796 histopathologically verified rectal adenocarcinomas diagnosed 2010-2015 in two counties in Sweden (population 630,000 in 2015) were identified. Staging with pelvic MRI unless contraindications were present, treatment and pathology followed Swedish guidelines.Patients and methods: All 796 histopathologically verified rectal adenocarcinomas diagnosed 2010-2015 in two counties in Sweden (population 630,000 in 2015) were identified. Staging with pelvic MRI unless contraindications were present, treatment and pathology followed Swedish guidelines.Results: Twenty-three % of cases (n = 186) had distant metastases at diagnosis, demonstrating more advanced tumor and nodal stages when compared with non-metastatic patients (p < 0.001), and they more often displayed MRI-identified mucinous features and extramural vascular invasion (EMVI) than non-metastatic tumors (p < 0.001 for both). In non-metastatic patients, 8% displayed clinical stage T1 (cT1), 21% cT2, and 53% cT3; one-third of the latter threatened or involved the mesorectal fascia (MRF+). Almost 20% had stage cT4 (4% cT4a, 14% cT4b) of which 50% were considered "non-resectable". EMVI was seen in 33% of cT3M0 tumors and in 48% of cT4M0 tumors.Conclusions: In an unselected population, approximately 80% of primary rectal cancers are referred to as "locally advanced" (stage or cT3-4 or N+), meaning that they, according to many international guidelines, are recommended neo-adjuvant treatment. This study provides a detailed description of the clinical stages and presence of characteristics identifiable on MRI which are of importance when assessing the needs for RT/CRT, when using different guidelines.
|
|
| 8. |
- Hammarström, Klara, 1990-
(författare)
-
Staging and therapy response in rectal cancer
- 2023
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Every year, around 2,200 individuals are diagnosed with rectal cancer in Sweden. As a result of better tumour staging using magnetic resonance imaging (MRI), pre-operative radiotherapy (with or without chemotherapy), and improved surgery, outcome has improved substantially during the past few decades. Today less than 5% of patients experience a local recurrence. Treatment response is highly variable, up to 30% of patients have a complete remission (CR) after pre-treatment while others do not benefit from the treatment. The aim of this thesis was to investigate factors associated with CR in rectal cancer as accurate response prediction already at the time of diagnosis could enable a personalized treatment approach. For this purpose, an unselected rectal cancer cohort of approximately 1,200 patients diagnosed between 2010-2018 was built. Paper I provides a description of tumour stages and other MRI characteristics required for the treatment decision in the rectal cancer cohort. In this unselected patient population, most tumours belonged to the risk groups with intermediate or high risk of recurrence and are thus recommended to pre-treatment.In Paper II, the proportions of patients recommended pre-treatment according to different guidelines were investigated to better understand the wide variability in treatment seen worldwide. This study concluded that between 38% and 77% of non-metastatic patients are presently recommended pre-operative treatment according to 15 international guidelines, when strictly applied to our non-selected rectal cancer cohort. To achieve a more personalized treatment approach and a stricter use of pre-treatment, predictive factors of tumour remission are needed. In Paper III an evaluation of the predictive capacity of all clinical and pathological factors used in the staging of rectal cancer prior to treatment decision was done. In Paper IV a combination of clinical and sequencing data was used in analyses to further assess associations with CR and which factors impact prognosis. Tumour size, stage, tumour marker CEA and treatment were predictive of CR. Moreover, genetic factors such as mutated SMAD4 and SYNE1 were associated with CR but further investigations are needed to determine clinical relevance. Mutated KRAS was an independent predictor of non-CR. BRAF V600E mutation increased the risk of recurrence.
|
|
| 9. |
- Herrera, Mercedes, et al.
(författare)
-
Prognostic Interactions between FAP plus Fibroblasts and CD8a+T Cells in Colon Cancer
- 2020
-
Ingår i: Cancers. - : MDPI. - 2072-6694. ; 12:11
-
Tidskriftsartikel (refereegranskat)abstract
- Simple Summary In addition to malignant cells, tumors are composed also of other cell types including immune cells and fibroblasts. These cell types interact with each other and with the malignant cells. Prognosis associations have previously been demonstrated for CD8-positive immune cells. Recent studies suggest that fibroblasts can affect the function of immune cells. The aim of this study was to investigate if the fibroblast composition of tumors affected the prognosis association of CD8 immune cells. This study demonstrated that in colon cancer, CD8 prognosis associations was restricted to the group of tumors with high expression the FAP fibroblast marker. Our findings suggest continued mechanistic studies regarding crosstalk between FAP-positive fibroblasts and the different immune cell types; and also support the investigation of fibroblast/T-cell interactions for therapeutic purposes. Inter-case variations in immune cell and fibroblast composition are associated with prognosis in solid tumors, including colon cancer. A series of experimental studies suggest immune-modulatory roles of marker-defined fibroblast populations, including FAP-positive fibroblasts. These studies imply that the fibroblast status of tumors might affect the prognostic significance of immune-related features. Analyses of a population-based colon cancer cohort demonstrated good prognosis associations of FAP intensity and CD8a density. Notably, a significant prognostic interaction was detected between these markers (p = 0.013 in nonadjusted analyses and p = 0.003 in analyses adjusted for cofounding factors) in a manner where the good prognosis association of CD8 density was restricted to the FAP intensity-high group. This prognostic interaction was also detected in an independent randomized trial-derived colon cancer cohort (p = 0.048 in nonadjusted analyses). In the CD8-high group, FAP intensity was significantly associated with a higher total tumor density of FoxP3-positive immune cells and a higher ratio of epithelial-to-stromal density of CD8a T cells. The study presents findings relevant for the ongoing efforts to improve the prognostic performance of CD8-related markers and should be followed by additional validation studies. Furthermore, findings support, in general, earlier model-derived studies implying fibroblast subsets as clinically relevant modulators of immune surveillance. Finally, the associations between FAP intensity and specific immune features suggest mechanisms of fibroblast-immune crosstalk with therapeutic potential.
|
|
| 10. |
- Imam, Israa, et al.
(författare)
-
Neoadjuvant rectal (NAR) score : Value evaluating the efficacy of neoadjuvant therapy and prognostic significance after surgery?
- 2021
-
Ingår i: Radiotherapy and Oncology. - : Elsevier. - 0167-8140 .- 1879-0887. ; 157, s. 70-77
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: The Neoadjuvant rectal (NAR) score is a new surrogate endpoint to be used in clinical trials for early determination of treatment response to different preoperative therapies. The aim is to further validate the NAR-score, primarily developed using chemoradiotherapy (CRT) with a delay to surgery 6-8 weeks, and explore its value using other schedules. Materials and Methods: The study included all 9978 patients diagnosed with non-metastasized RC in 2007-2015 that had undergone surgery and was registered in the Swedish Colorectal Cancer Registry. The patients of interest had either short-course radiotherapy (scRT)/CRT + delayed surgery, longcourse radiotherapy (RT) + delayed surgery, (C)RT + additional chemotherapy, primary surgery, or scRT + immediate surgery. The scRT/CRT + delayed surgery groups were further divided based on time to surgery. Results: Mean NAR-score differed significantly (p < 0.0001) between different treatments. (C) RT + additional chemotherapy had the lowest mean score of 16.3 and CRT + delayed surgery had 17.7. There was a significant difference (p < 0.05) in overall survival (OS) and time to recurrence (TTR) of patients with a Low NAR-score (<8) compared to those with a High score (>16) for both CRT- and scRT, with a stronger correlation for CRT-patients. C-index for the NAR-score model (0.623) was not superior to when only pathological T- and N-stage was used (0.646). Conclusions: The NAR-score is prognostic, but it is not better than pT- and pN-stage. However, the NARscore can still discriminate between two treatments that have different cell killing effect and may still be of value in clinical trials as an easier method than pT- and N-stage.
|
|
