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Biomedical subjects

Olav Dahl

Publications and source records attributed to Olav Dahl.

31 records · Page 2Linked to original sources
PubMed2004

Conformal radiotherapy of urinary bladder cancer.

Recent advances in radiotherapy (RT) are founded on the enhanced tumour visualisation capabilities of new imaging modalities and the precise deposition of individualised radiation dose distributions made possible with the new systems for RT planning and delivery. These techniques have a large potential to also improve the results of RT of urinary bladder cancer. Major challenges to take full advantage of these advances in the management of bladder cancer are to control, and, as far as possible, reduce bladder motion, and to reliably account for the related intestine and rectum motion. If these obstacles are overcome, it should be possible in the near future to offer selected patients with muscle invading bladder cancer an organ-sparing, yet effective combined-modality treatment as an alternative to radical surgery.

Humans↗
PubMed2004

Evaluation of a new method for calculation of cumulative doses in the rectum wall using repeat CT scans.

The rectum wall is an important organ at risk during irradiation of the prostate, the bladder and other organs in the pelvis. It is therefore of great interest to be able reliably to predict normal tissue complication probabilities (NTCPs) for this organ. Because the rectum wall is a hollow organ capable of large deformations between fractions, dose estimates from a single CT are unreliable, and thereby also NTCP estimates. In this study two methods for calculations of cumulative dose distributions from repetitive CT scans are compared. The first is a method presented in this article that uses tracking of volume elements for a direct summation of the doses delivered in the treatment fractions. The other, presented earlier (1), is based on information from dose-volume histograms. The comparisons were made in terms of equivalent uniform doses (EUDs) and NTCPs. The methods were also compared with mean values of EUD and NTCP values from individual CT scans. The study showed that with the relatively symmetric beam arrangements normally used for treatment of prostate and bladder cancer, it is not necessary to use the more laborious method of element tracking. However, an introduction of artificial lateral rectum movements revealed that element tracking is necessary in less symmetric situations.

Carcinoma, Transitional Cell↗
PubMed2004

Transient CEA increase at start of oxaliplatin combination therapy for metastatic colorectal cancer.

In general a rising carcinoembryonic antigen (CEA) level means tumor progression. We observed a transient increase in CEA level despite objective response among patients receiving chemotherapy for metastatic colorectal cancer. This surge phenomenon has not previously been described for patients with metastatic colorectal disease. CEA was measured every second week in 27 patients receiving oxaliplatin, 5-fluororuracil, and folinic acid as first-line therapy against metastatic colorectal cancer. Four patients (15%, 95% CI 5-31%) met the criteria for therapy-induced CEA surge. The time of reaching maximum CEA level varied from 13 to 56 days. Median rise in CEA from baseline was 263% (range 24-632%). An initial rise of CEA during chemotherapy in colorectal cancer patients may therefore not always indicate progression of disease but may be a transient CEA surge in patients responding to chemotherapy.

Adult↗
PubMed2003

Organ motion, set-up variation and treatment margins in radical radiotherapy of urinary bladder cancer.

BACKGROUND AND PURPOSE: A major challenge in conformal radiotherapy of bladder cancer is to determine adequate treatment margins. For this purpose, we therefore quantified the internal motion of the urinary bladder as well as the external patient set-up variation during a course of fractionated radiotherapy. In the light of the recently introduced ICRU-62 concept, the planning organ at risk volume, we also studied the internal motion of nearby organs at risk, the rectum and intestine. MATERIAL AND METHODS: Weekly CT scans and electronic portal images (EPIs) were sampled from 20 patients during radical, conformal bladder irradiation (60-64 Gy/2 Gy in five fractions weekly). The planning scans were acquired with 70 ml of bladder contrast instilled, and patients were instructed to void before the treatment/repeat scanning sessions. Internal motion of the bladder, rectum and intestine was measured by 3-D image matching of the repeat scans to the patients' planning scans. Internal margins (CTV-to-ITV) were determined using both a direct empirical approach and an analytically derived margin recipe. The external patient set-up variability was determined by 2-D matching of front and lateral EPIs to corresponding digitally reconstructed radiographs. RESULTS: A total of 149 CT scans (20 for planning, 129 during the treatment course) and 133 sets of EPIs were analysed. Bladder volumes were smaller during treatment than in the planning situation in 85% of the repeat scans. Nevertheless, we found the repeat scan bladder volumes to extend outside the planning scan bladder contours in 89% of the scans, on average with 9% of the volume (range: 0-47%). Eight patients (40%) had at least one repeat scan (25 scans in total) where displacements >15 mm were observed at one or more sides of the bladder. CTV-to-ITV margins of 10 mm inferior, 20 mm superior, 11 mm left, 8 mm right, 20 mm anterior and 14 mm posterior were required to simultaneously encompass all bladder deflections except for the largest outward deflection in all directions in 84% of the patients. Including patient set-up variation (CTV-to-PTV), we found that an additional safety margin of 2-6 mm had to be added in the various directions. The rectum expanded outside the planning contours in all repeat scans, on average with 24% of the volume (range: 2-69%). The volume of intestine found close to the bladder were significantly and negatively correlated to the bladder volume in almost half of the patients. CONCLUSION: This study documented both a large internal motion of the bladder and a substantial patient set-up variation. Our current treatment margins have been adjusted according to the findings of this study. Considerable variation in position and volume of the rectum and intestine was also documented.

Aged↗
PubMed2003

Brachytherapy for prostate cancer: a systematic review of clinical and cost effectiveness.

OBJECTIVES: Brachytherapy is emerging as a new treatment option for prostate cancer, and is increasingly being used in Europe and North America. METHODS: A systematic review of studies that compared clinical or cost effectiveness of prostate brachytherapy with radical prostatectomy or external beam radiation for patients with localised prostate cancer. RESULTS: No randomised controlled trials were identified, but five observational studies with comparable patient groups were included in the review. There were no valid data on overall or disease-free survival. There was no difference in disease-free survival based on PSA as a surrogate measure, or in rates of complications. No cost effectiveness studies were found. Based on Norwegian data, the one-year cost of the three treatment options seem fairly similar, while long term cost data are lacking due to lack of data on long term clinical outcome. CONCLUSION: The evidence on the clinical effectiveness of therapies for localised prostate cancer is scarce, but the outcome appears to be comparable for radical prostatectomy, external beam radiotherapy and brachytherapy.

Aged↗
PubMed2003

Gonadal hormones in long-term survivors 10 years after treatment for unilateral testicular cancer.

OBJECTIVE: To investigate whether unilaterally orchiectomised testicular cancer survivors (TCSs) are more likely to display reduced Leydig cell function than healthy males. METHODS: A national multi-centre survey of 1235 TCSs was performed in 1998-2000 (mean age: 44 years) treated between 1980 and 1994 (mean follow-up: 11 years). Serum hormone analyses were performed on 1183 TCSs, as 52 TCSs used androgen replacement (AR). TCSs were allocated to four treatment groups: Surgery only (251); Radiotherapy only (515); Chemotherapy 1, cisplatin </=850 mg (373); Chemotherapy 2, cisplatin >850 mg (96). The Controls were represented by 200 healthy blue-collar workers (mean age: 44 years). LH >12 IU/l and testosterone <8 nmol/l and the use of AR indicated hypogonadism. RESULTS: Serum testosterone was similar in TCSs and Controls (16.9 vs.17.1 nmol/l), but TCSs had higher age-adjusted LH levels than the Controls (5.2 vs. 3.5 IU/l). LH increased with treatment intensity, but was elevated even in TCSs treated with surgery only. The age-adjusted odds ratio of hypogonadism was 3.8 (95%CI: 2.0-7.3) in TCSs, and increased with treatment intensity. CONCLUSION: TCSs are at risk to develop pre-mature reduced Leydig cell function and hypogonadism. They may therefore be predisposed for the syndrome of androgen deficiency of aging males (ADAM).

Adolescent↗
PubMed2003

Profiles and time course of acute radiation toxicity symptoms during conformal radiotherapy for cancer of the prostate.

Symptoms of gastrointestinal toxicity are dose-limiting for pelvic radiotherapy (RT). Existing toxicity registrations (RTOG/EORTC) are helpful in defining maximal tolerated doses, but tend to underestimate the total toxicity burden by excluding several minor complaints. We have applied a more detailed and quantitative recording of symptoms and related these scores to RT-induced endoscopic and histopathologic changes. Prevalence and severity of specific toxicity symptoms were recorded before, during (weeks 2 and 6) and 2 and 8 weeks after RT in 96 patients undergoing external beam RT for localized prostate cancer. RTOG/EORTC acute toxicity and ad hoc total toxicity scores (TTS) were recorded. TTS scores were calculated by adding scores based on visual analog scale (VAS) grading of individual symptoms Fifty of the patients also underwent sequential proctoscopy with mucosal biopsy. Individual symptoms increased, but differed in prevalence and intensity during and after RT TTS increased during the entire treatment course in spite of normalizing histopathologic and endoscopic changes from week 2 onwards. Twenty-seven patients had no RTOG/EORTC toxicity, four had grade 3 and none had grade 4 toxicity. All patients with grade 0 had increased TTS. Thus, TTS appeared more sensitive than RTOG/EORTC scoring. The study demonstrates that multiple toxicity symptoms contribute to total toxicity in response to pelvic RT. TTS is a feasible and sensitive method for detecting and quantifying acute toxicity and unveils morbidity which remains hidden with the RTOG/EORTC score system. The development and timing of symptoms may give clues to pathogenesis, treatment, and prophylaxis.

Aged↗
PubMed2003

Nordic 5-fluorouracil/leucovorin bolus schedule combined with oxaliplatin (Nordic FLOX) as first-line treatment of metastatic colorectal cancer.

This study combined oxaliplatin with the Nordic bolus schedule of 5-fluorouracil (5-FU) and folinic acid (FA) as first-line treatment in metastatic colorectal cancer. Twenty-seven patients were treated every second week with oxaliplatin 85 mg/m2 as a 2-h infusion on day 1, followed by a 3-min bolus injection with 5-FU 500 mg/m2 and 30 min later a bolus injection with FA 60 mg/m2 given on days 1 and 2. Seventeen patients achieved a complete (n = 2) or partial (n = 15) response, leading to a confirmed response rate of 63% (95% CI 45-81%). The estimated median times to progression and survival were 8.9 and 18.7 months, respectively. Neutropenia grade 3-4 toxicity was seen in 63% of patients, neuropathy grade 3 in one patient and grade 2 in 12 patients. Oxaliplatin combined with the bolus Nordic schedule of 5-FU/ FA (Nordic FLOX) appears to be well tolerated, effective and feasible as first-line treatment of metastatic colorectal cancer yielding results comparable with those obtained by more complex schedules.

Adenocarcinoma↗
PubMed2002

[Brachytherapy in prostatic cancer].

BACKGROUND: Brachytherapy is increasingly used in the treatment of early prostate cancer, but has not been implemented as a treatment option in Norway. Recent advances in imaging techniques and the radiation technology itself has facilitated improvements in and better standardisation of brachytherapy. MATERIAL AND METHODS: An group of expert assisted the Norwegian Centre for Health Technology Assessment (SMM) in a systematic review of the evidence on the clinical effectiveness of prostate brachytherapy. The literature was identified by a defined search strategy, and assessed for relevance and validity. Only controlled or comparative studies were included in the review. RESULTS: There were no randomized controlled trials or large prospective studies. Many of the relevant studies were of poor validity. None of the included studies had sufficient follow-up for overall or disease free survival. There were no differences between brachytherapy, external beam therapy or radical prostatectomy in disease free survival (PSA measures) or in rates of complications. INTERPRETATION: There is a lack of valid data from large prospective studies on the clinical effectiveness of brachytherapy. On the other hand, the clinical effectiveness of radical prostatectomy and external beam radiotherapy is also poorly documented. Results from one large randomized controlled trial comparing radical prostatectomy with brachytherapy in the USA will not be available within the next ten years.

Brachytherapy↗
PubMed2002

The influence of combretastatin A-4 and vinblastine on interstitial fluid pressure in BT4An rat gliomas.

The influence of combretastatin A-4 disodium phosphate (CA-4, 50mg/kg intraperitoneally (i.p.)) and vinblastine (2mg/kg i.p.) on interstitial fluid pressure (IFP) was assessed in BT4An rat gliomas implanted subcutaneously in the neck. Furthermore the growth inhibitory effect of vinblastine and the distribution of fluorescence-conjugated vinblastine (BODIPY-vinblastine) were investigated. Tumors at different volumes were compared. Whereas CA-4 had no major influence on IFP, independent of tumor size, vinblastine increased the IFP in neoplasms above 8 cm(3) (P=0.03). Vinblastine yielded a significant tumor response only in tumors below 2.1 cm(3) (P=0.03). The distribution of BODIPY-vinblastine was heterogeneous and comparable despite tumor volume differences. We conclude that the influence of vinblastine on IFP is more pronounced than that of CA-4 in BT4An neck tumors, and that vinblastine may reduce subsequent drug delivery to solid tumors by increasing the IFP.

Animals↗
PubMed2002

Cardiac and pulmonary doses and complication probabilities in standard and conformal tangential irradiation in conservative management of breast cancer.

BACKGROUND AND PURPOSE: The clinical benefit of irradiating the intact breast after lumpectomy must be weighted against the risk of severe toxicity. We present a study on cardiac and pulmonary dose-volume data and the related complication probabilities of tangential breast irradiation having the following objectives: (1) to quantify the sparing of the organs at risk (ORs), the heart and the lung, achieved by three-dimensional (3-D) conformal tangential irradiation (CTI) as compared to standard tangential irradiation (STI); (2) to elucidate the uncertainty in radiation tolerance data; and (3) to analyse the relation between the amount of OR irradiated and the resulting morbidity risk. MATERIAL AND METHODS: Computed tomography (CT)-based 3-D treatment plans of 26 patients prescribed to CTI of the intact breast were applied. Contour-based STI has been our routine treatment, and was reconstructed for all patients. Dose-volume data and normal tissue complication probability (NTCP) predictions from the probit and relative seriality models with several cardiac and pulmonary tolerance parameterizations were analysed and compared. RESULTS AND CONCLUSIONS: A significant amount of normal tissues can be spared from radiation by using CT-based CTI, resulting in a 50% reduction of the average excess cardiac mortality risk in the left-sided cases. The risks for pericarditis and pneumonitis were too low to reveal any clinically significant difference between the treatments. For the STI set-up, a regression analysis showed that the excess cardiac mortality risk increased when larger parts of the heart were inside the fields. However, the different excess cardiac mortality and pneumonitis tolerance parameters resulted in statistically significant different NTCPs, which precluded the ability to accurately predict absolute NTCPs after tangential breast irradiation. Despite this uncertainty the different series of cardiac and pulmonary risk predictions were in relatively good agreement when small volumes of the ORs were irradiated. From the present data and without consideration of patient or organ motion, it therefore appears that tangential breast irradiation with less than 1 cm of the heart and 2-2.5 cm of the lung included inside the treatment fields will cause at most 1 per thousand risk for cardiac mortality and pulmonary morbidity. CT-based CTI should be considered, in particular for the left-sided cases, if these requirements cannot be met.

Adult↗
PubMed2002

Norwegian oncologists' expectations of intensity-modulated radiotherapy.

AIthough intensity-modulated radiotherapy (IMRT) may increase the therapeutic ratio of radiotherapy for a range of malignancies, only a few IMRT treatments have yet been performed in the Nordic countries. The scores derived from a national survey to assess Norwegian oncologists' expectations of IMRT are presented. A questionnaire was distributed to all consultants in oncology at Norwegian radiotherapy clinics. Summary scores of daily general radiotherapy workload (DGRTW), acquaintance with IMRT (AI) and expectations of IMRT (EI) were derived. Thirty-nine questionnaires (67%) were returned from a total of 58 oncologists. The oncologists' scores on the AI scale (mean score: 7.5 out of 21) were rather low. Their AI scores were found to be positively correlated with their DGRTW. Higher scores on the EI scale were documented (mean score: 6.2 out of 14): 15 oncologists (39%) rated IMRT as one of the three major contributors to potentially increased cancer survival. Oncologists treating patients with prostate, head and neck, gastrointestinal and CNS tumours had higher EI scores than the other oncologists (7.7 vs. 5.1; p = 0.01). The Norwegian radiation oncologists' expectations of IMRT are high in terms of both the potential clinical benefit and the rate of implementation. This should encourage the radiotherapy communities to continue (or rapidly initiate) their efforts in providing the routines required for safe implementation of IMRT.

Attitude of Health Personnel↗