| 1. |
- Arving, Cecilia, 1961-
(författare)
-
Individual psychosocial support for breast cancer patients : Quality of life, psychological effects, patient satisfaction, health care utilization and costs
- 2007
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A randomized intervention study, with the aim to compare the effects of individual psychosocial support provided by (1) oncology nurses specially trained in psychological techniques (INS), or (2) psychologists (IPS), to (3) standard care (SC). Breast cancer patients, living in Uppsala County, and about to start adjuvant treatment at the Department of Oncology, Uppsala, were consecutively included between 1998 and 2000. The patients were assessed seven times during two years by self-administered questionnaires. Study I revealed positive effects of both INS and IPS as compared to SC on global quality of life, side effects, and post-traumatic distress. A lower proportion of patients in the intervention groups had psychosocial support provided in routine care compared with the SC group. In study II the patients reported being highly satisfied with the intervention, irrespective of profession providing the support. However, patients in the INS group reported higher levels of benefit regarding disease-related problems than those in the IPS group. In study III total Health Care costs were lower in the intervention groups and since a gain in quality-adjusted life years (QALY) was seen (mean .1 QALY), the interventions dominated. The costs for the interventions were 44 291- 48 978 SEK. In study IV, daily reporting of anxiety, depression and activity on Visual Analogue Scales (VAS) were completed during two weeks before and after the Hospital Anxiety and Depression Scale (HADS) assessments. A point assessment with the HADS captured the situation better than four weeks assessment on three VAS in the diary. The HADS was considered preferable to the diary. The conclusion is that psychosocial support is beneficial for breast cancer patients and that the intervention delivered by nurses was as effective as that given by psychologists. The costs for the interventions were limited.
|
|
| 2. |
- Birgisson, Helgi, 1967-
(författare)
-
Cancer of the Colon and Rectum : Population Based Survival Analysis and Study on Adverse Effects of Radiation Therapy for Rectal Cancer
- 2006
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The Swedish Cancer Register was used to determine the relative survival rate in colon and rectal cancer and to estimate the occurrence of second cancers related to radiation therapy for rectal cancer. The Swedish Hospital Discharge Register and hospital records were used to estimate the rate of late adverse effects due to radiation therapy for rectal cancer. The whole Swedish population was the source of the survival studies. Patients participating in the Uppsala Trial and the Swedish Rectal Cancer Trial on radiation therapy for rectal cancer constituted the subjects of the studies on late adverse effects and second cancers.The main results of the survival analysis revealed a significant improvement in the 5-year relative survival rate for both colon and rectal cancer. During the time period 1960-1999, the survival improved from 39.6% to 57.2% in colon cancer and from 36.1% to 57.6% in rectal cancer.Patients irradiated for rectal cancer, in addition to surgery, were at increased risk for a second cancer compared to those treated by surgery alone. This risk increase was mainly found for cancers developing in organs within or adjacent to the irradiated target (relative risk (RR) 2.04; 95% confidence interval (CI) 1.10–3.79). Furthermore, the most important late adverse effects of radiation therapy seem to be those on the gastrointestinal tract, in the form of small bowel obstruction (RR 1.88; 95%CI 1.10–3.20) and abdominal pain (RR 1.92; 95% CI 1.14–3.23). Overall, the benefit of radiation therapy was greater than its drawbacks, as a large reduction in local recurrences and better survival was noted in patients treated preoperatively with irradiation for rectal cancer.In conclusion, significant improvements in the survival of patients with colon and rectal cancers have occurred in the last decades, especially in patients with rectal cancer. These improvements probably are related to advances in surgical and adjuvant treatment. The radiation therapy has several drawbacks, however, including an increased risk of second cancers and of bowel obstruction. This emphasises the need to further improve the radiation technique and to select only those patients for radiation therapy who are most likely to benefit from it.
|
|
| 3. |
- Cavalli-Björkman, Nina, 1970-
(författare)
-
Factors Influencing Selection of Treatment for Colorectal Cancer Patients
- 2012
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In Sweden and elsewhere there is evidence of poorer cancer survival for patients of low socioeconomic status (SES), and in some settings differences in treatment by SES have been shown.The aim of this thesis was to explore factors which influence cancer treatment decisions, such as knowledge reaped from clinical trials, patient-related factors, and physician-related factors. In a register study of colorectal cancer, all stages, patients were stratified for SES-factors. Differences were seen with regards to clinical investigation, surgical and oncological treatment and survival, with the highly educated group being favored. Survival was better for highly educated patients in stages I, II and III but not in stage IV.In a Scandinavian cohort of newly metastasized colorectal cancer patients, recruitment to clinical trials was studied. Patients entering clinical trials had better performance status and fewer cancer symptoms than those who were treated with chemotherapy outside of a clinical trial. Median survival was 21.3 months for trial-patients and 15.2 months for those treated with chemotherapy outside a trial. Those not treated with chemotherapy had a median survival of just 2.1 months. Patients in clinical trials are highly selected and conclusions drawn from studies cannot be applied to all patients.In the same cohort, treatment and survival were stratified for education, smoking and indicators of social structure. Highly educated patients did not have a survival advantage. Patients who lived alone were offered less combination chemotherapy and surgery of metastases than other patients and had 4 months shorter survival than those who lived with a spouse or child. In a fourth study, 20 Swedish gastrointestinal oncologists were interviewed on which factors they considered when deciding on oncological treatment. Oncologists feared chemotherapy complications due to lack of social support, and ordered less combination chemotherapy for patients living alone. Highly educated patients were seen as well-read and demanding, and giving in to these patients’ requests for treatment was regarded as a way of pleasing patients and relatives and of avoiding conflict.
|
|
| 4. |
- Folkesson, Joakim, 1969-
(författare)
-
Rectal Cancer : Can the Results be Further Improved?
- 2006
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The treatment of rectal cancer is complex and comprises: diagnostic measures; different preoperative treatments; a multitude of surgical and technical choices; possibilities of postoperative treatments and postoperative care and follow up. In this thesis, some aspects of this complex paradigm have been further investigated. One of the most feared complications after rectal cancer surgery is anastomotic leakage. The risk of anastomotic leakage is affected by non-influenceable factors related to the tumour and the patient. In the first paper, the risk of anastomotic leakage in relation to a surgical instrument, the circular stapler, was investigated. The risk of leakage was 7% or 11%, depending on the choice of instrument. In the second paper, a long-term evaluation of survival and local recurrence rates in the Swedish Rectal Cancer Trial was made. Randomisation was to either preoperative radiotherapy followed by surgery or surgery alone. After 13 years median follow-up, survival was 38% in the radiotherapy group and 30% in the surgery alone group. Differences in local recurrence rates were seen in all stages. Most rectal cancer operations carry a high risk of morbidity and mortality. For early stage cancers, a local procedure may be sufficient and in the third paper, population-based results of local excision of rectal cancer were explored. In stage I, cancer specific survival was the same after local excision as after major resection, but the relative survival was lower. The risk of local recurrence was higher after local excision than after resections. In the fourth paper, differences in survival rates in the Nordic countries and Scotland were investigated. The relative excess risk of death was highest in Denmark, but only in the first 90 postoperative days. Through applying already existing knowledge and successively introducing new treatments, the results for rectal cancer treatment will be further improved.
|
|
| 5. |
- 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.
|
|
| 6. |
- Häggblad Sahlberg, Sara, 1980-
(författare)
-
Colorectal cancer and radiation response : The role of EGFR, AKT and cancer stem cell markers
- 2014
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The primary treatment for colorectal cancer is surgery. Radiotherapy and chemotherapy, sometimes combined, are also frequently used to diminish recurrence risk. In response to radiation exposure, several cellular signaling cascades are activated to repair DNA breaks, prevent apoptosis and to keep the cells proliferating. Several proteins in the radiation response and cell survival pathways are potential targets to enhance the effects of radiation. The epidermal growth factor receptor (EGFR), which is frequently upregulated in colorectal cancer and exhibits a radiation protective function, is an attractive target for treatment. EGFR is activated by radiation which in turn activates numerous signaling pathways such as the PI3 kinase/AKT cascade, the RAS/RAF/ERK pathway and STAT leading to tumor cell proliferation. EGFR is also believed to interact with proteins in the DNA repair process, such as DNA-PKcs and MRE11. The cytotoxic effect of an affibody molecule (ZEGFR:1907)2, with high affinity to EGFR, in combination with radiation produced a small, but significant, reduction in survival in a KRAS mutated cell line. However, not in the BRAF mutated cell line. The next step was therefore to target proteins downstream of EGFR such as AKT. There was an interaction between AKT and the DNA repair proteins DNA-PKcs and MRE11 and both AKT1 and AKT2 were involved in the radiation response. The knockout of both AKT isoforms impaired the DNA double strand break rejoining after radiation and suppression of DNA-PKcs increased the radiations sensitivity and decreased the DNA repair further. The AKT isoforms also affected the expression of cancer stem cell markers CD133 and CD44 which are associated with the formation of metastasis as well as radiation and drug resistance. The CD133 expression was associated with AKT1 but not AKT2, whereas the CD44 expression was influenced by the presence of either AKT1 or AKT2. AKT was also involved in cell migration, cell-adhesion and metabolism. Overall, these results illustrate the complexity in response to radiation and drugs in cells with different mutations and the need for combining inhibitors against several targets such as EGFR, AKT, DNA-PKcs, CD133 or CD44.
|
|
| 7. |
- Jestin, Pia, 1955-
(författare)
-
Colorectal Cancer : Audit and Health Economy in Colorectal Cancer Surgery in a Defined Swedish Population
- 2005
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Colorectal cancer is one of the most common malignancies in Sweden, with more than 5000 new cases annually. Median age at time of diagnosis is approximately 75 years. Owing to the ageing population, the incidence of colorectal cancer is increasing. The improvement in surgical technique and the introduction of adjuvant radio- and chemotherapy increased the 5-year survival rate from approximately 30-40% in the early 1960s to almost 60% in the late 1990s. The cost of public health care has risen considerably, and case-costing systems are increasingly demanded. Linked to clinical guidelines and quality registers, such control systems form a proper basis for quality assurance projects and improvement. The aim of this thesis is to describe the efficiency and cost effectiveness of colorectal cancer treatment in a defined Swedish population. Emergency surgery for colon cancer, constituting 25% of the cases, increased both mortality and cost. Among emergency cases there was not only an increase in postoperative mortality but also a stage specific decrease in long-term survival rate. Correct staging is decisive for further treatment of patients after colon cancer surgery and influences long-term survival. The number of lymph nodes examined varied between different pathology departments and could be used as a quality measurement. The proportion of tumour stage III increased the more nodes examined. A prognostic estimation of stage III cases that is less sensitive to the number of nodes examined is proposed. A case-control study aimed at identifying risk factors for anastomotic leakage after rectal cancer surgery confirmed previously known risk factors but failed to identify further steps during the perioperative course that were amenable to improvement. This research has confirmed that population-based quality and case-costing registers, linked to clinical guidelines, constitute a proper source for projects of quality improvement and decisions about distribution of resources in health care.
|
|
| 8. |
- Johansson, Jonas, 1970-
(författare)
-
Comparative Treatment Planning in Radiotherapy and Clinical Impact of Proton Relative Biological Effectiveness
- 2006
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The development of new irradiation techniques is presently a very active field of research with increased availability of more sophisticated modalities such as intensity modulated photons (IMRT), protons and light ions. The primary aim of this work is to evaluate if the dose-distributions using IMRT and protons contribute to clinical advantages. A secondary aim is to investigate the potential clinical implication of the increased relative biological effect (RBE) for protons at the end of the Bragg peak. The potential benefits are evaluated using physical dose measures and dose-response models for normal tissue complication probability (NTCP) and tumour control probability (TCP). Comparative treatment planning was performed using three locally advanced tumour types, left-sided node positive breast cancer, hypopharyngeal cancer, and rectal cancer. All studies showed that both IMRT and protons could improve the dose distributions compared to 3D-CRT, and significantly improve treatment results with lower NTCPs and, concerning hypopharyngeal cancer, higher TCP. Protons always resulted in smaller volumes receiving intermediate and low radiation doses.Using protons or IMRT for left-sided node-positive breast cancer, the advantage is a significantly decreased risk for cardiac mortality (from 6.7% to 1%) and radiation induced pneumonitis (from 28.2% to less than 3%) compared to 3D-CRT. For hypopharyngeal cancer, protons and IMRT provide more selective treatment plans, higher TCP since a simultaneous boost technique is feasible, and better parotid gland sparing for several patients. For locally advanced rectal cancer, the NTCP for small bowel is potentially reduced by approximately 50% using IMRT or protons; protons have an even greater potential if the structure of the small bowel is parallel.A variable RBE correction is developed and applied to a clinical proton treatment plan. A significant difference is obtained compared to the commonly accepted RBE correction of 1.1. This indicates that a variable RBE may be of importance in future proton treatment planning.This thesis provides support for increased use both IMRT and proton radiotherapy, although stronger for protons. Therefore, investments in proton facilities with capacity for large clinical trials can be supported.
|
|
| 9. |
- Kimstrand, Peter, 1975-
(författare)
-
Beam Modelling for Treatment Planning of Scanned Proton Beams
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Scanned proton beams offer the possibility to take full advantage of the dose deposition properties of proton beams, i.e. the limited range and sharp peak at the end of the range, the Bragg peak. By actively scanning the proton beam, laterally by scanning magnets and longitudinally by shifting the energy, the position of the Bragg peak can be controlled in all three dimensions, thereby enabling high dose delivery to the target volume only. A typical scanned proton beam line consists of a pair of scanning magnets to perform the lateral beam scanning and possibly a range shifter and a multi-leaf collimator (MLC). Part of this thesis deals with the development of control, supervision and verification methods for the scanned proton beam line at the The Svedberg laboratory in Uppsala, Sweden.Radiotherapy is preceded by treatment planning, where one of the main objectives is predicting the dose to the patient. The dose is calculated by a dose calculation engine and the accuracy of the results is of course dependent on the accuracy and sophistication of the transport and interaction models of the dose engine itself. But, for the dose distribution calculation to have any bearing on the reality, it needs to be started with relevant input in accordance with the beam that is emitted from the treatment machine. This input is provided by the beam model. As such, the beam model is the link between the reality (the treatment machine) and the treatment planning system. The beam model contains methods to characterise the treatment machine and provides the dose calculation with the reconstructed beam phase space, in some convenient representation. In order for a beam model to be applicable in a treatment planning system, its methods have to be general.In this thesis, a beam model for a scanned proton beam is developed. The beam model contains models and descriptions of the beam modifying elements of a scanned proton beam line. Based on a well-defined set of generally applicable characterisation measurements, ten beam model parameters are extracted, describing the basic properties of the beam, i.e. the energy spectrum, the radial and the angular distributions and the nominal direction. Optional beam modifying elements such as a range shifter and an MLC are modelled by dedicated Monte Carlo calculation algorithms. The algorithm that describes the MLC contains a parameterisation of collimator scatter, in which the rather complex phase space of collimator scattered protons has been parameterised by a set of analytical functions.Dose calculations based on the phase space reconstructed by the beam model are in good agreement with experimental data. This holds both for the dose distribution of the elementary pencil beam, reflecting the modelling of the basic properties of the scanned beam, as well as for complete calculations of collimated scanned fields.
|
|
| 10. |
- Nordberg, Erika, 1980-
(författare)
-
EGFR and HER2 Targeting for Radionuclide-Based Imaging and Therapy : Preclinical Studies
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The optimal way to detect and treat cancer is to target cancer cells exclusively without affecting the surrounding tissue. One promising approach is to use radiolabelled molecules to target receptors that are overexpressed in cancer cells. Since the epidermal growth factor receptor (EGFR) family is overexpressed in many types of cancer, it is an attractive target for both diagnostic and therapeutic applications. This thesis can be divided into two parts. In part one (paper I), studies were conducted to modulate radionuclide uptake in tumour cells. The results showed that it was possible to modulate the cellular uptake of 125I delivered by trastuzumab (targeting HER2) by adding EGF (targeting EGFR). In part two (papers II-V) a high affinity EGFR-targeting affibody molecule (ZEGFR:955)2 was selected and analysed both in vitro and in vivo. In papers II, III and V, the results obtained when using (ZEGFR:955)2 were compared with those obtained with the two EGFR-binding molecules, EGF and cetuximab. These studies demonstrated that the affibody molecule bound specifically to EGFR (probably to subdomain III) with high affinity (~50 nM in biosensor analysis and ~1 nM in cellular studies) and produced intracellular signalling changes similar to those with cetuximab. In paper IV, in vivo studies were made, demonstrating that [111In](ZEGFR:955)2 gave a tumour-specific 111In uptake of 3.8±1.4% of injected dose per gram tumour tissue, 4 h post-injection. The tumours could be easily visualized with a gamma camera at this time-point. The results of these studies indicated that the affibody molecule (ZEGFR:955)2 is a possible candidate for radionuclide-based imaging of EGFR-expressing tumours. The biological effects of (ZEGFR:955)2 might be of interest for therapy applications.
|
|
