Uncertainties are inevitably part of the radiotherapy process. Uncertainty in the dose deposited in the tumour exists due to organ motion, patient positioning errors, fluctuations in machine output, delineation of regions of interest, the modality of imaging used, and treatment planning algorithm assumptions among others; there is uncertainty in the dose required to eradicate a tumour due to interpatient variations in patient-specific variables such as their sensitivity to radiation; and there is uncertainty in the dose-volume restraints that limit dose to normal tissue. This thesis involves three major streams of research including investigation of the actual dose delivered to target and normal tissue, the effect of dose uncertainty on radiobiological indices, and techniques to display the dose uncertainty in a treatment planning system. All of the analyses are performed with the dose distribution from a four-field box treatment using 6 MV photons. The treatment fields include uniform margins between the clinical target volume and planning target volume of 0.5 cm, 1.0 cm, and 1.5 cm. The major work is preceded by a thorough literature review on the size of setup and organ motion errors for various organs and setup techniques used in radiotherapy. A Monte Carlo (MC) code was written to simulate both the treatment planning and delivery phases of the radiotherapy treatment. Using MC, the mean and the variation in treatment dose are calculated for both an individual patient and across a population of patients. In particular, the possible discrepancy in tumour position located from a single CT scan and the magnitude of reduction in dose variation following multiple CT scans is investigated. A novel convolution kernel to include multiple pretreatment CT scans in the calculation of mean treatment dose is derived. Variations in dose deposited to prostate and rectal wall are assessed for each of the margins and for various magnitudes of systematic and random error, and penumbra gradients. The linear quadratic model is used to calculate prostate Tumour Control Probability (TCP) incorporating an actual (modelled) delivered prostate dose. The Kallman s-model is used to calculate the normal tissue complication probability (NTCP), incorporating actual (modelled) fraction dose in the deforming rectal wall. The impact of each treatment uncertainty on the variation in the radiobiological index is calculated for the margin sizes. / Thesis (Ph.D.)--Department of Physics and Mathematical Physics, 2002.

Radiation film dosimetry process using the RIT 113 v.4 dosimetry software and the film digitizer VXR-l2plus was used to evaluate the accuracy of electron dose calculations of the RAHD radiation therapy treatment planning system at Samaritan Regional Cancer Center. Kodak Ready-Pack EDR-2 film is recommended for dose distribution analysis in clinically practical dose ranges. The pencil-beam algorithm has a limitation for calculating dose in the penumbra region and in the tail region where the dose falls off. / Graduation date: 2005

A 9.4 T magnetic resonance imaging (MRI) system was used to evaluate the response of a human tumour xenograft model to radiation therapy. The apparent diffusion coefficient (ADC) and the transverse relaxation time (T2) of human glioblastoma multiforme (GBM) tumour xenografts in NIH-iii nude mice were measured before, and at multiple points after, treatment of the tumours with 200 kVp x-rays. The response was characterized as a function of a number of variables of interest in the clinical treatment of cancer with external beam radiation therapy. Mean tumour ADC and T2 responses after single fractions of radiation were investigated, with measurements being made until 14 days after treatment. Single fraction doses ranged from 50 cGy to 800 cGy. Fractionated treatments were used to deliver 800 cGy in two or three fractions with fraction spacings of 24 or 72 hours. The role of hypoxia on ADC and T2 response was investigated by using an externally-applied, suture-based ligature to induce a state of reduced oxygenation in tumours during treatment, after which ADC and T2 were measured using serial MRI. Finally, tumours were dissected in order to provide insight into possible pathophysiological mechanisms explaining the observed responses. Tissue sections were prepared and reviewed by a pathologist. This work adds to the body of literature describing tumour ADC and T2 response to anticancer therapy, and adds to the understanding of ADC and T2 response to radiation therapy in particular. This works supports that of others suggesting the use of ADC and T2 as potential biomarkers for tumour response to treatment. / Medical Physics

New methods of high dose delivery, such as intensity modulated radiation therapy (IMRT), stereotactic radiation therapy (SRT) or stereotactic radiosurgery (SRS), hadron therapy, tomotherapy, etc., all make use of a few large fractions. To improve these treatments, there are three main directions: (i) improving physical dose distribution, (ii) optimizing radiosurgery dose-time scheme and (iii) modifying dose response of tumors or normal tissues. Different radiation modalities and systems have been developed to deliver the best possible physical dose to the target while keeping radiation to normal tissue minimum. Although applications of radiobiological findings to clinical practice are still at an early stage, many studies have shown that   sublethal radiation damage repair kinetics plays an important role in tissue response to radiation. The purpose of the present thesis is to show how the above-mentioned directions could be used to improve treatment outcomes with special interest in radiation modalities and dose-time scheme, as well as radiobiological modeling. Also for arteriovenous malformations (AVM), the possible impact of AVM network angiostructure in radiation response was studied. / Nya och förbättrade metoder för precisionsbestrålning, såsom intensitetsmodulerad strålbehandling (IMRT), stereotaktisk strålbehandling (SRT), stereotaktisk strålkirurgi (SRS) eller hadronterapi etc., gör det möjligt att leverera behandlingen i ett fåtal fraktioner med höga doser. Dessa behandlingmetoder kan ytterligare förbättras genom att (i) förbättra den fysikaliska dosfördelningen, (ii) optimera dosrater och fraktioneringsscheman eller (iii) modifiera dosresponsen hos tumörer eller normalvävnad. Olika strålmodaliteter och behandlingssystem har tagits fram för att kunna leverera bästa möjliga fysikaliska dosfördelning till targetvolymen samtidigt som dosen till frisk vävnad hålls så låg som möjligt. Även om användandet av radiobiologisk kunskap och modeller i klinisk rutin ännu är i sin linda så visar många studier att kinetiken för subletal reparation av strålskador har stor betydelse för strålresponsen. Syftet med denna avhandling är att visa hur dessa olika utvecklingsvägar kan användas för att förbättra behandlingsresultatet speciellt genom att studera vald strålmodalitet, dosrat och fraktioneringsschema samt radiobiologisk modellering. För arteriovenösa missbildningar (AVM) har även  studerats hur strukturen hos angionätverket påverkar strålresponsen. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Manuscript. Paper 4: Manuscript.</p>

Radiotherapy is a potential curative option for liver cancer; however, respiratory motion creates uncertainty in treatment delivery. Advances in imaging and registration techniques can provide information regarding changes in respiratory motion. Currently image registration is challenged by computation and manual intervention. A Navigator Channel (NC) technique was developed to overcome these limitations. A population motion model was generated to predict patient-specific motion, while a point motion detection technique was developed to calculate the patient-specific liver edge motion from images. An adaptation technique uses the relative difference between the population and patient calculated liver edge motion to determine the patient's liver volume motion. The NC technique was tested on patient 4D-CT images for initial validation to determine the accuracy. Accuracy was less than 0.10 mm in liver edge detection and approximately 0.25 cm in predicting patient-specific motion. This technique can be used to ensure accurate treatment delivery for liver radiotherapy.

Radiotherapy is a potential curative option for liver cancer; however, respiratory motion creates uncertainty in treatment delivery. Advances in imaging and registration techniques can provide information regarding changes in respiratory motion. Currently image registration is challenged by computation and manual intervention. A Navigator Channel (NC) technique was developed to overcome these limitations. A population motion model was generated to predict patient-specific motion, while a point motion detection technique was developed to calculate the patient-specific liver edge motion from images. An adaptation technique uses the relative difference between the population and patient calculated liver edge motion to determine the patient's liver volume motion. The NC technique was tested on patient 4D-CT images for initial validation to determine the accuracy. Accuracy was less than 0.10 mm in liver edge detection and approximately 0.25 cm in predicting patient-specific motion. This technique can be used to ensure accurate treatment delivery for liver radiotherapy.

Background and aim: Many patients with cancer experience emesis (nausea and vomiting) during radiotherapy. The overall aim of this thesis was to improve the situation for patients with risk for emesis during radiotherapy, by evaluating emesis in patients receiving verum (genuine) acupuncture, sham (simulated) acupuncture or standard care during radiotherapy. Methods: In study I, a cross-sectional sample (n=368) treated with radiotherapy over various fields answered a study-specific questionnaire. In study II, 80 healthy volunteers were randomized to receive needling with verum acupuncture or non-penetrating telescopic sham needles by one of four physiotherapists. In study III, 215 patients were randomly allocated to verum (n=109) or non-penetrating telescopic sham (n=106) acupuncture during their entire radiotherapy period over abdominal or pelvic fields. The same 215 patients were also included in study IV. They were compared to 62 patients irradiated over abdominal or pelvic fields, selected from study I. Results: In study I, the weekly prevalence of nausea was 39 % in all radiotherapy-treated patients and 63 % in abdominal or pelvic irradiated patients. Age younger than 40 years and previous experience of nausea in other situations were characteristics associated with an increased risk for nausea. Of the 145 nauseous patients, 34 % considered their antiemetic treatment as insufficient. Patients with nausea reported lower level of quality of life compared to patients free from nausea. In study II, most individuals needled with verum (68 %) or sham (68 %) acupuncture could not identify needling type, and that blinding result varied from 55 to 80 % between the four therapists. In study III, nausea was experienced by 70 % (mean number of days=10.1) and 25 % vomited during the radiotherapy period. In the sham group 62 % experienced nausea (mean number of days=8.7) and 28 % vomited. Ninety five percent in the verum and 96 % in the sham group believed that the treatment had been effective for nausea. In both groups, 67 % experienced other positive effects, on relaxation, mood, sleep or pain-reduction, and 89 % were interested in receiving the treatment again. In study IV, the weekly prevalence of nausea and vomiting was 38 and 8 % in the verum group, 37 and 7 % in the sham group and 63 and 15 % in the standard care group. The nausea difference between the acupuncture and the standard care cohort was statistically significant, also after overall adjustments for potential confounding factors. The nausea intensity in the acupuncture cohort was lower compared to the standard care cohort (p=0.002). Patients who expected nausea had increased risk for nausea compared to patients who expected low risk for nausea (Relative risk 1.6). Conclusions and implications: Nausea was common during abdominal or pelvic field irradiation in patients receiving standard care. Verum acupuncture did not reduce emesis compared to sham acupuncture, while reduced emesis was seen in both patients treated with verum or sham acupuncture. Health-care professionals may consider identifying and treating patients with increased risk for nausea in advance. The telescopic sham needle was credible. Researchers may thus use and standardize the sham procedure in acupuncture control groups. The choice of performing acupuncture during radiotherapy cannot be based on arguments that the specific characters of verum acupuncture have effects on nausea. It is important to further study what components in the acupuncture procedures that produce the dramatic positive but yet not fully understood antiemetic effect, making it possible to use those components to further increase quality of care during radiotherapy.

No description available.

Although there had been some improvement of treatment results by the combination of concurrent chemoradiotherapy with esophagectomy, the overall prognosis for patients with esophageal cancer remained poor. Selection of optimal treatment strategy for individual patients would be improved by an objective biomarker that can predict prognosis accurately. The aim of this prospective study was to evaluate whether serum concentration of C-reactive protein (CRP) can be used as a prognostic factor to predict the survival of esophageal cancer patients treated with radiotherapy. Between Nov 2002 and July 2007, patients undergoing radiotherapy for newly diagnosed esophageal cancer were eligible for inclusion into this study. Serum CRP concentration was measured prospectively before the initiation of treatment. The relationship between the serum CRP levels and clinicopathological parameters were analyzed retrospectively. The prognosis factors of esophageal cancer were statistically determined. A total of 123 patients consisting of 120 males and 3 females were enrolled in this study. 81 patients (65.9%) had high CRP levels (greater than 5 mg/L). Patients with CRP levels higher than 5 mg/L had a shorter overall survival (P < 0.001). The 2-year survival was 78.4% for patients with CRP < 5 mg/L compared with 7.8% with CRP¡Ù5 mg/L. Hypoalbuminemia (albumin< 3.5g/dL) was significantly related to shorter survival in univariate analysis. Multivariate analysis demonstrated that higher serum CRP concentration and hypoalbuminemia were both independent prognostic factors for esophageal cancer. Pretreatment serum CRP and albumin levels are easily measurable biomarkers and are significant prognostic factors for esophageal cancer. They can be used in combination with the conventional staging system to predict survival and stratify patients with esophageal cancer treated with radiotherapy more accurately.

The purpose of this study is to evaluate the health related quality of life (QoL) of head and neck cancer (HNC) patients with cancer-free survival after treatment and to investigate the factors correlated with their health-related QoL. The European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) questionnaire and the EORTC head and neck cancer-specific questionnaire (QLQ H&N-35) were self-administered by all participating patients. Sociodemographic data were collected using a questionnaire specifically designed for the study and through the medical chart reviewed. The patients who have been treated radiotherapy in our department of radiation oncology were invited to participate Health-related quality of life was assessed 3 months or later after completion of radiotherapy. Data relating to sociodemographic factors, disease characteristics and treatment factors of HNC survivors were analyzed. A total of 141 head and neck cancer patients completed the questionnaires. After data analysis, the results are described as follows: In the results of EORTC QLQ-C30 questionnaire, the score of ¡§global health status¡¨ is 69.34. Most of the patient could maintain good functional quality of life. ¡§Fatigue¡¨ is the most impaired symptom score in the patient. In the results of EORTC QLQ-H&N35, the three head and neck specific symptom scores indicating the most impaired in QOL were ¡§Weight loss¡¨, ¡§Nutrition supplements¡¨ and ¡§dry mouth¡¨. After analysis through the multiple regression model, we found sex, age, tumor subsite, radiotherapy technique and surgery were the independent factors significantly correlated with the QoL scales This study is helpful for us to understand the QoL status and the factors affecting the QoL for patients with head and neck cancer after radiotherapy.