| 1. |
- Aho, Sonja, et al.
(författare)
-
Impact of Primary Tumor Location on Demographics, Resectability, Outcomes, and Quality of Life in Finnish Metastatic Colorectal Cancer Patients (Subgroup Analysis of the RAXO Study)
- 2024
-
Ingår i: Cancers. - : MDPI. - 2072-6694. ; 16:5
-
Tidskriftsartikel (refereegranskat)abstract
- Simple Summary The location of the primary tumor in the right colon, left colon, or rectum affects the efficacy of biological drugs used in the treatment of metastatic colorectal cancer, but how? We examined how the primary tumor location affects disease characteristics, treatability, quality of life, and outcome in a real-life study population of 1080 Finnish patients in the RAXO study. The primary tumor location correlates with the location of metastases, the frequency of gene mutations, how often metastases can be operated upon, long-term survival after curative surgery or palliative chemotherapy, and the quality of life during the disease trajectory. The primary tumor location is a helpful surrogate for clinicians working with metastatic colorectal cancer patients in estimating the clinical course of the disease. This study cannot identify the reasons for the associations, i.e., whether it is the primary location per se, the different mutations, or other reasons.Abstract The primary tumor location (PTL) is associated with the phenotype, metastatic sites, mutations, and outcomes of metastatic colorectal cancer (mCRC) patients, but this has mostly been studied according to sidedness (right vs. left sided). We studied right colon vs. left colon vs. rectal PTL in a real-life study population (n = 1080). Health-related quality of life (HRQoL) was assessed multi-cross-sectionally with QLQ-C30, QLQ-CR29, EQ-5D, and 15D. A chi-square, Kaplan-Meier, and Cox regression were used to compare the groups. The PTL was in the right colon in 310 patients (29%), the left colon in 396 patients (37%), and the rectum in 375 patients (35%). The PTL was associated with distinct differences in metastatic sites during the disease trajectory. The resectability, conversion, and resection rates were lowest in the right colon, followed by the rectum, and were highest in the left colon. Overall survival was shortest for right colon compared with left colon or rectal PTL (median 21 vs. 35 vs. 36 months), with the same trends after metastasectomy or systemic therapy only. PTL also remained statistically significant in a multivariable model. The distribution of symptoms varied according to PTL, especially between the right colon (with general symptoms of metastases) and rectal PTL (with sexual- and bowel-related symptoms). mCRC, according to PTL, behaves differently regarding metastatic sites, resectability of the metastases, outcomes of treatment, and HRQoL.
|
|
| 2. |
- Ali, Abir Salwa, et al.
(författare)
-
Intravenous versus oral etoposide : efficacy and correlation to clinical outcome in patients with high-grade metastatic gastroenteropancreatic neuroendocrine neoplasms (WHO G3)
- 2018
-
Ingår i: Medical Oncology. - : Springer. - 1357-0560 .- 1559-131X. ; 35:4
-
Tidskriftsartikel (refereegranskat)abstract
- High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs, G3) are aggressive cancers of the digestive system with poor prognosis and survival. Platinum-based chemotherapy (cisplatin/carboplatin + etoposide) is considered the first-line palliative treatment. Etoposide is frequently administered intravenously; however, oral etoposide may be used as an alternative. Concerns for oral etoposide include decreased bioavailability, inter-and intra-patient variability and patient compliance. We aimed to evaluate possible differences in progression-free survival (PFS) and overall survival (OS) in patients treated with oral etoposide compared to etoposide given as infusion. Patients (n = 236) from the Nordic NEC study were divided into three groups receiving etoposide as a long infusion (24 h, n = 170), short infusion (= 5 h, n = 33) or oral etoposide (n = 33) according to hospital tradition. PFS and OS were analyzed with Kaplan-Meier (log-rank), cox proportional hazard ratios and confidence intervals. No statistical differences were observed in PFS or OS when comparing patients receiving long infusion (median PFS 3.8 months, median OS 14.5 months), short infusion (PFS 5.6 months, OS 11.0 months) or oral etoposide (PFS 5.4 months, OS 11.3 months). We observed equal efficacy for the three administration routes suggesting oral etoposide may be safe and efficient in treating high-grade GEP-NEN, G3 patients scheduled for cisplatin/carboplatin + etoposide therapy.
|
|
| 3. |
- Cindemir, Umut, et al.
(författare)
-
Sputter-Deposited Indium-Tin Oxide Thin Films for Acetaldehyde Gas Sensing
- 2016
-
Ingår i: Coatings. - : MDPI AG. - 2079-6412. ; 6:2
-
Tidskriftsartikel (refereegranskat)abstract
- Reactive dual-target DC magnetron sputtering was used to prepare In-Sn oxide thin films with a wide range of compositions. The films were subjected to annealing post-treatment at 400 degrees C or 500 degrees C for different periods of time. Compositional and structural characterizations were performed by X-ray photoelectron spectroscopy, energy dispersive X-ray spectroscopy, X-ray diffraction, Rutherford backscattering and scanning electron microscopy. Films were investigated for gas sensing at 200 degrees C by measuring their resistance response upon exposure to acetaldehyde mixed with synthetic air. We found that the relative indium-to-tin content was very important and that measurable sensor responses could be recorded at acetaldehyde concentrations down to 200 ppb, with small resistance drift between repeated exposures, for both crystalline SnO2-like films and for amorphous films consisting of about equal amounts of In and Sn. We also demonstrated that it is not possible to prepare crystalline sensors with intermediate indium-to-tin compositions by sputter deposition and post-annealing up to 500 degrees C.
|
|
| 4. |
- Forsgård, Richard A., 1987-, et al.
(författare)
-
Chemotherapy-induced gastrointestinal toxicity is associated with changes in serum and urine metabolome and fecal microbiota in male Sprague-Dawley rats
- 2017
-
Ingår i: Cancer Chemotherapy and Pharmacology. - : Springer. - 0344-5704 .- 1432-0843. ; 80:2, s. 317-332
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Chemotherapy-induced gastrointestinal toxicity (CIGT) is a complex process that involves multiple pathophysiological mechanisms. We have previously shown that commonly used chemotherapeutics 5-fluorouracil, oxaliplatin, and irinotecan damage the intestinal mucosa and increase intestinal permeability to iohexol. We hypothesized that CIGT is associated with alterations in fecal microbiota and metabolome. Our aim was to characterize these changes and examine how they relate to the severity of CIGT.Methods: A total of 48 male Sprague-Dawley rats were injected intraperitoneally either with 5-fluorouracil (150 mg/kg), oxaliplatin (15 mg/kg), or irinotecan (200 mg/kg). Body weight change was measured daily after drug administration and the animals were euthanized after 72 h. Blood, urine, and fecal samples were collected at baseline and at the end of the experiment. The changes in the composition of fecal microbiota were analyzed with 16S rRNA gene sequencing. Metabolic changes in serum and urine metabolome were measured with 1 mm proton nuclear magnetic resonance (1H-NMR).Results: Irinotecan increased the relative abundance of Fusobacteria and Proteobacteria, while 5-FU and oxaliplatin caused only minor changes in the composition of fecal microbiota. All chemotherapeutics increased the levels of serum fatty acids and N(CH3)(3) moieties and decreased the levels of Krebs cycle metabolites and free amino acids.Conclusions: Chemotherapeutic drugs, 5-fluorouracil, oxaliplatin, and irinotecan, induce several microbial and metabolic changes which may play a role in the pathophysiology of CIGT. The observed changes in intestinal permeability, fecal microbiota, and metabolome suggest the activation of inflammatory processes.
|
|
| 5. |
- Forsgård, Richard A., 1987-, et al.
(författare)
-
Intestinal permeability to iohexol as an in vivo marker of chemotherapy-induced gastrointestinal toxicity in Sprague-Dawley rats
- 2016
-
Ingår i: Cancer Chemotherapy and Pharmacology. - : Springer. - 0344-5704 .- 1432-0843. ; 78:4, s. 863-874
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Gastrointestinal toxicity is the most common adverse effect of chemotherapy. Chemotherapeutic drugs damage the intestinal mucosa and increase intestinal permeability. Intestinal permeability is one of the key markers of gastrointestinal function and measuring intestinal permeability could serve as a useful tool for assessing the severity of chemotherapy-induced gastrointestinal toxicity.Methods: Male Sprague-Dawley rats were injected intraperitoneally either with 5-fluorouracil (150 mg/kg), oxaliplatin (15 mg/kg) or irinotecan (200 mg/kg). Clinical signs of gastrointestinal toxicity were assessed daily by weighing the animals and by checking for diarrhea. After 48 h, intestinal permeability to iohexol was measured in vivo by giving the animals 1 ml of 647 mg/ml iohexol solution by oral gavage and collecting all the excreted urine for 24 h. All of the animals were euthanized 72 h after drug administration and tissue samples were harvested from the jejunum and colon.Results: All chemotherapeutics caused significant body weight loss and diarrhea. Intestinal permeability to iohexol was also increased in all treatment groups and histological analysis revealed significant intestinal damage in both jejunum and colon. Iohexol permeability correlated with the severity of clinical signs of gastrointestinal toxicity and with acute colonic injury.Conclusions: Chemotherapeutic drugs, such as 5-fluorouracil, oxaliplatin, and irinotecan, increase intestinal permeability to iohexol. Measuring intestinal permeability to iohexol could provide a simple marker for assessing chemotherapy-induced gastrointestinal toxicity.
|
|
| 6. |
- Forsgård, Richard A., 1987-, et al.
(författare)
-
Two-Week Aflibercept or Erlotinib Administration Does Not Induce Changes in Intestinal Morphology in Male Sprague-Dawley Rats But Aflibercept Affects Serum and Urine Metabolic Profiles
- 2019
-
Ingår i: Translational Oncology. - : Elsevier. - 1944-7124 .- 1936-5233. ; 12:8, s. 1122-1130
-
Tidskriftsartikel (refereegranskat)abstract
- Gastrointestinal toxicity is a frequently observed adverse event during cancer treatment with traditional chemotherapeutics. Currently, traditional chemotherapeutics are often combined with targeted biologic agents. These biologics, however, possess a distinct toxicity profile, and they may also exacerbate the adverse effects of traditional chemotherapeutics. In this study, we aimed to characterize the gastrointestinal and metabolic changes after a 2-week treatment period with aflibercept, an antiangiogenic VEGFR decoy, and with erlotinib, a tyrosine-kinase inhibitor. Male rats were treated either with aflibercept or erlotinib for 2 weeks. During the 2-week treatment period, the animals in the aflibercept group received twosubcutaneous doses of 25 mg/kg aflibercept. The erlotinib group got 10 mg/kg of erlotinib by oral gavage every other day. The control groups were treated similarly but received either saline injections or oral gavage of water. Intestinal toxicity was assessed by measuring intestinal permeability and by histological analyses of intestinal tissues. Metabolic changes were measured with H-1 nuclear magnetic resonance in serum and urine. Neither aflibercept nor erlotinib induced changes in intestinal permeability or intestinal tissue morphology. However, aflibercept treatment resulted in stunted body weight gain and altered choline, amino acid, and lipid metabolism. Two-week treatment with aflibercept or erlotinib alone does not induce observable changes in gastrointestinal morphology and function. However, observed aflibercept-treatment related metabolic changes suggest alterations in intestinal microbiota, nutrient intake, and adipose tissue function. The metabolic changes are also interesting in respect to the systemic effects of aflibercept and their possible associations with adverse events caused by aflibercept administration.
|
|
| 7. |
- Holm, Matilda, et al.
(författare)
-
Detection of KRAS mutations in liquid biopsies from metastatic colorectal cancer patients using droplet digital PCR, Idylla, and next generation sequencing
- 2020
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:11
-
Tidskriftsartikel (refereegranskat)abstract
- Circulating tumor DNA (ctDNA) is released from cancer cells and oncogenic mutations in ctDNA can be measured from plasma samples. Droplet digital PCR (ddPCR) is a sensitive and specific method for the detection of mutations in ctDNA. We analyzed serial plasma samples (n = 80) from ten metastatic colorectal cancer (mCRC) patients with a known KRAS mutation in their primary tumor. The patients were undergoing oncological treatment with bevacizumab in combination with alternating capecitabine and oxaliplatin or irinotecan. Baseline ddPCR KRAS mutation allele frequency (MAF) values ranged from 0% to 63%. The first radiologic response evaluation criteria in solid tumors (RECIST) evaluation was performed 45-63 days after the initiation of treatment, and by this time three patients had an undetectable level of KRAS mutation, one had a MAF value of 0.5%, and one had a MAF value of 3% that had been reduced by 95% from the baseline value. In three of these patients the RECIST assessment was stable disease and in two partial response. In seven patients, ddPCR MAF values increased before radiological disease progression or death, while one patient remained disease-free with an undetectable KRAS mutation level. Next, we analyzed all available plasma samples with the Idylla ctKRAS system (n = 60), and found that the overall degree of agreement between ddPCR and Idylla was almost perfect (kappa value = 0.860). We used next-generation sequencing (NGS) to detect treatment-induced mutations in the last serial plasma sample of each patient, but were unable to find any new mutations when compared to the primary tumor. This study shows that ddPCR and Idylla are equally efficient for the detection of KRAS mutations in the liquid biopsies from mCRC patients and that ctDNA may indicate the disappearance of treatment responsive KRAS positive mCRC clones and serve as an early sign of disease progression.
|
|
| 8. |
- Kinos, Sampsa, et al.
(författare)
-
Detailed analysis of metastatic colorectal cancer patients who developed cardiotoxicity on another fluoropyrimidine and switched to S-1 treatment (subgroup analysis of the CardioSwitch-study)
- 2024
-
Ingår i: Acta Oncologica. - : Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63, s. 248-258
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: The CardioSwitch-study demonstrated that patients with solid tumors who develop cardiotoxicity on capecitabine or 5-fluorouracil (5-FU) treatment can be safely switched to S-1, an alternative fluoropyrimidine (FP). In light of the European Medicines Agency approval of S-1 in metastatic colorectal cancer (mCRC), this analysis provides more detailed safety and efficacy information, and data regarding metastasectomy and/or local ablative therapy (LAT), on the mCRC patients from the original study.Materials and methods: This retrospective cohort study was conducted at 12 European centers. The primary endpoint was recurrence of cardiotoxicity after switch. For this analysis, safety data are reported for 78 mCRC patients from the CardioSwitch cohort (N = 200). Detailed efficacy and outcomes data were available for 66 mCRC patients.Results: Data for the safety of S-1 in mCRC patients were similar to the original CardioSwitch cohort and that expected for FP-based treatment, with no new concerns. Recurrent cardiotoxicity (all grade 1) with S-1-based treatment occurred in 4/78 (5%) mCRC patients; all were able to complete FP treatment. Median progression-free survival from initiation of S-1-based treatment was 9.0 months and median overall survival 26.7 months. Metastasectomy and/or LAT was performed in 33/66 (50%) patients, and S-1 was successfully used in recommended neoadjuvant/conversion or adjuvant-like combination regimens and schedules as for standard FPs.Interpretation: S-1 is a safe and effective FP alternative when mCRC patients are forced to discontinue 5-FU or capecitabine due to cardiotoxicity and can be safely used in the standard recommended regimens, settings, and schedules.
|
|
| 9. |
- Lambert, Paul C., et al.
(författare)
-
Temporal trends in the proportion cured for cancer of the colon and rectum : a population-based study using data from the Finnish Cancer Registry
- 2007
-
Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 121:9, s. 2052-2059
-
Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer is the third most common cancer worldwide and the second most common cancer in Europe. Cumulative relative survival curves for both cancer of the colon and cancer of the rectum generally plateau after approximately 6-8 years. When this occurs, "population" or "statistical" cure is reached. We analyzed data from the Finnish Cancer Registry over a 50-year period using methods that simultaneously estimate the proportion of patients cured of disease (the cure fraction) and the survival time distribution of the "uncured" group. Our primary aim was to investigate temporal trends in the cure fraction and median survival of the uncured by age group for both cancer of the colon and rectum. For both cancers, the cure fraction has increased dramatically over time for all age groups. However, the difference in the cure fraction between age groups has reduced over time, particularly for cancer of the colon. Median survival in the uncured has also increased over time in all age groups but there still remains an inverse relationship between age and median survival, with shorter median survival with increasing age. The reasons for these impressive increases in patient survival are complex, but are highly likely to be strongly related to many improvements in cancer care over this same time period.
|
|
| 10. |
|
|
