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Olav Dahl

Publications and source records attributed to Olav Dahl.

At least 19 recordsLinked to original sources

Paternity following treatment for testicular cancer.

BACKGROUND: Studies of fertility in men treated for testicular cancer have mainly addressed serum follicle-stimulating hormone levels and sperm parameters. We assessed post-treatment paternity among long-term survivors of testicular cancer. METHODS: Men (n = 1814) who had been treated for unilateral testicular cancer in Norway during 1980 through 1994 were invited to participate in a national multi-center follow-up survey in 1998 through 2002. The participants were allocated to five groups according to the treatment received after orchiectomy, including treatment at relapse (surveillance, retroperitoneal lymph node dissection, radiotherapy, low-dose chemotherapy [i.e., < or = 850 mg cisplatin], and high-dose chemotherapy [i.e., > 850 mg cisplatin]). Cox proportional hazards analysis was used to assess predictive factors for post-treatment paternity. Statistical tests were two-sided. RESULTS: A total of 1433 men were assessable, of whom 827 were fathers at diagnosis. Post-treatment conception was attempted by 554 men, among whom the overall 15-year actuarial post-treatment paternity rate was 71% (95% confidence interval [CI] = 66% to 75%) without the use of cryopreserved semen. This rate ranged from 48% (95% CI = 30% to 69%) in the high-dose chemotherapy group to 92% (95% CI = 78% to 98%) in the surveillance group (P < .001). The median actuarial time from diagnosis to the birth of the first child after treatment was 6.6 years overall but varied according to treatment. Assisted reproductive technologies were used by 22% of the couples who attempted conception after treatment. Dry ejaculation, treatment group, pretreatment fatherhood, and marital status were statistically significant independent predictors for post-treatment fatherhood, with dry ejaculation as the most important negative factor. CONCLUSIONS: Although the overall paternity rate after treatment for testicular cancer was high, the ability to conceive and the time to conception reflected the intensity of treatment. These data may help inform patients about their future ability to father biological children.

Actuarial Analysis↗

First results of triple-modality treatment combining radiotherapy, chemotherapy, and hyperthermia for the treatment of patients with stage IIB, III, and IVA cervical carcinoma.

BACKGROUND: Patients with advanced cervical carcinoma are treated routinely with radiotherapy and cisplatin-containing chemotherapy. It has been shown that hyperthermia can improve the results of both radiotherapy and cisplatin. In the current study, the feasibility and efficacy of the combination of all three modalities was studied in previously untreated patients with cervical carcinoma. METHODS: Patients with advanced cervical carcinoma were registered prospectively in the U.S., Norway, and the Netherlands. External-beam radiotherapy and brachytherapy were administered for a biologically effective dose > or = 86.7 gray. At least 4 courses of weekly cisplatin (40 mg/m(2)) and 4 sessions of weekly locoregional hyperthermia were added to radiotherapy. RESULTS: Sixty-eight patients with a median age of 45 years were enrolled. Full-dose radiotherapy was delivered to all patients according to plan. At least 4 courses of chemotherapy were received by 97% of patients, and at least 4 courses of hyperthermia treatment were received by 93% of patients. Toxicity was fully comparable to that described for chemoradiotherapy alone, and the median total treatment time was 45 days. Complete remission was achieved by 61 patients (90%). After a median follow-up of 538 days, 74% of patients remained alive without signs of recurrence, and the overall survival rate was 84%. CONCLUSIONS: The combination of full-dose radiotherapy, chemotherapy, and hyperthermia was feasible and effective in a multicenter international setting among patients with advanced cervical carcinoma. A Phase III study comparing this novel triplet with standard chemoradiation, designed to show at least a 15% improvement in overall survival, has been launched.

Adult↗

Side effects and cancer-related stress determine quality of life in long-term survivors of testicular cancer.

PURPOSE: The prevalence of long-term survivors after treatment for testicular cancer (TC) is increasing, and most studies display normal or only slightly reduced quality of life (QOL) in TC survivors (TCSs). Impaired QOL is claimed to be associated with treatment modality and its side effects, although most studies in this field can be criticized for various methodologic shortcomings. We wanted to examine variation in long-term QOL in TCSs in relation to TC treatment modality, side effects, and TC-related stress in a large population. PATIENTS AND METHODS: QOL, side effects, and TC-related stress were self-rated by a questionnaire at a mean of 11 years of follow-up in 1,409 TCSs treated from 1980 to 1994. Norm data was obtained from 2,678 males who were representative of the general population. QOL was measured with the Short Form-36 (SF-36), and TC-related stress was measured with the Impact of Event Scale. RESULTS: There were no clinically relevant differences in QOL between TCSs and age-adjusted norm data, although there was a slightly lowered SF-36 Physical Component Summary Score in TCSs. Variation of QOL in TCSs was related to self-reported side effects and TC-related stress but not to TC treatment modality. A significant association was found between side effects and TC-related stress. CONCLUSION: TCSs do not suffer long term from reduced QOL, and only minor differences in QOL were found between different treatment modalities. TCSs who report more side effects or TC-related stress have increased risk for reduced QOL, but these associations are not explained by TC treatment modalities. Further QOL research in this area should explore vulnerability factors for side effects and TC-related stress.

Adult↗

Study of anxiety disorder and depression in long-term survivors of testicular cancer.

PURPOSE: To increase our knowledge of the prevalence of anxiety disorder and depression in long-term testicular cancer survivors (TCSs), and to identify variables associated with such caseness. PATIENTS AND METHODS: Participants were 1,408 TCSs treated between 1980 and 1994 in Norway. Participants provided information about their medical, social, and familial situation on a questionnaire. They also completed the Hospital Anxiety and Depression Scale (HADS). Anxiety disorder and depression were defined by a score >/= 8 on the HADS subscales. The prevalence rates were compared with age-adjusted norm data. RESULTS: HADS-defined anxiety disorder was more prevalent in TCSs (19.2%; 95% CI, 17.2% to 21.3%) than in the norm sample (13.5%; 95% CI, 13.1% to 13.9%; P < .001), whereas the prevalence of HADS-defined depression did not differ from the norm (TCSs, 9.7%; 95% CI, 8.1% to 11.2% v norm, 10.1%, 95% CI, 9.5 to 10.5; P = .56). The relative risk for anxiety disorder was 1.49 (95% CI, 1.31 to 1.69) and for depression the relative risk was 0.96 (95% CI, 0.81 to 1.14) in TCSs compared with norm. In multivariate analyses, HADS-defined anxiety disorder in TCSs was associated with young age, peripheral neuropathy, economic problems, alcohol problems, sexual problems, relapse anxiety, and having been treated for mental problems. CONCLUSION: Long-term TCSs have an increased risk of HADS-defined anxiety disorder that warrants clinical attention. Checking easily available demographic and TC-related data and use of a simple screening test such as HADS assists the identification of TCSs with anxiety disorder.

Adult↗

The association between self-reported physical activity and prevalence of depression and anxiety disorder in long-term survivors of testicular cancer and men in a general population sample.

GOALS OF WORK: Physical activity is claimed to have a beneficial influence on a person's mental health, though its impact may be different in cancer patients and individuals in the general population. The objective of this cross-sectional study was (1) to estimate the associations between the level of self-reported physical activity as a lifestyle factor (LPA) and the prevalence of depression and anxiety disorder in testicular cancer survivors (TCSs) and in men of similar age from the general population (GenPop), and (2) to examine whether these associations differ in the two groups. PATIENTS AND METHOD: A total of 1260 TCSs and 20,207 men from the GenPop completed a questionnaire that assessed LPA, and depression and anxiety disorder on the Hospital Anxiety and Depression Scale (HADS). MAIN RESULTS: The prevalence of HADS-defined depression was lower among those who were physically active than in those who were physically inactive (TCSs 9% vs 17%, P<0.001; GenPop 8% vs 15%, P<0.001). Among physically inactive TCSs there was a trend towards higher a prevalence of HADS-defined anxiety disorder compared to physically active TCSs (P=0.07). In the GenPop this difference was statistically significant (P<0.001). Multivariate analysis confirmed the association between LPA and HADS-defined depression in both the TCSs [adjusted odds ratio (aOR)=0.56; 95% confidence interval (CI) (0.31, 1.02)] and the GenPop [aOR=0.58; 95% CI (0.51, 0.65)], but not the association between LPA and HADS-defined anxiety disorder. The associations between LPA and HADS-defined depression and HADS-defined anxiety disorder did not differ between the TCSs and the GenPop. CONCLUSION: In both the TCSs and the GenPop, the prevalence of HADS-defined depression was higher among those who were physically inactive than among those who were physically active, with no intergroup difference. There was no association between LPA and prevalence of HADS-defined anxiety disorder in either of the groups after adjusting for background variables. Prospective studies are needed to allow causal inferences to be drawn.

Adult↗

Testing the new ICRU 62 'Planning Organ at Risk Volume' concept for the rectum.

BACKGROUND AND PURPOSE: To study the impact of the new ICRU 62 'Planning organ at Risk Volume' (PRV) concept on the relationship between rectum dose-volume histogram (DVH) data and toxicity. PATIENTS AND METHODS: The acute gastro-intestinal (GI) RTOG toxicity in 127 prostate cancer patients prescribed a total dose of 70 Gy with conformal irradiation to either the prostate, the prostate and seminal vesicles or the whole pelvis (initial 50 Gy only) were analysed. DVHs were derived for the rectum only and for rectum extended with six PRV margin sets (narrow/intermediate/wide; anterior/anterior and posterior). The data was analysed using permutation tests, logistic regression and effective uniform dose (EUD) calculations. RESULTS: Acute Grade 2 GI toxicity was seen in 22 of 127 cases (17%). Permutation tests showed that the difference between DVHs for patients with and without Grade 2 effects was significant, both for rectum only and rectum PRVs (P-value range: 0.02-0.04), with generally lower P-values for the PRVs. In the logistic regression, the fractional DVH variables (i.e. volumes) were significantly related to toxicity, with approximately 2-3 times as many significant dose levels for the PRVs as for rectum only. E.g. with wide anterior and posterior margins (16 and 11 mm, respectively) the relation was significant at 26 different dose levels (6-7, 13-14, 35-43, 60-71 and 73 Gy), compared to nine levels (38-40, 43-44 and 71-74 Gy) for rectum only. EUDs were significantly different for patients with and without Grade 2 effects both for rectum only and the PRVs (95% confidence interval for EUD increase with Grade 2 effects: 0.1-3.1 Gy). CONCLUSIONS: All statistical methods applied indicated a small, but definite difference in DVH parameters between patients with versus those without Grade 2 effects. The difference was most pronounced when margins of 16 mm anterior and 11 mm posterior were applied.

Humans↗

Adjuvant chemotherapy in colorectal cancer: a joint analysis of randomised trials by the Nordic Gastrointestinal Tumour Adjuvant Therapy Group.

Due to uncertainties regarding clinically meaningful gains from adjuvant chemotherapy after colorectal cancer surgery, several Nordic Groups in the early 1990s initiated randomised trials to prove or reject such gains. This report gives the joint analyses after a minimum 5-year follow-up. Between October 1991 and December 1997, 2 224 patients under 76 years of age with colorectal cancer stages II and III were randomised to surgery alone (n = 1 121) or adjuvant chemotherapy (n = 1 103) which varied between trials (5FU/levamisole for 12 months, n = 444; 5FU/leucovorin for 4-5 months according to either a modified Mayo Clinic schedule (n = 262) or the Nordic schedule (n = 397). Some centres also randomised patients treated with 5FU/leucovorin to+/-levamisole). A total of 812 patients had colon cancer stage II, 708 colon cancer stage III, 323 rectal cancer stage II and 368 rectal cancer stage III. All analyses were according to intention-to-treat. No statistically significant difference in overall survival, stratified for country or region, could be found in any group of patients according to stage or site. In colon cancer stage III, an absolute difference of 7% (p = 0.15), favouring chemotherapy, was seen. The present analyses corroborate a small but clinically meaningful survival gain from adjuvant chemotherapy in colon cancer stage III, but not in the other presentations.

Adenocarcinoma↗

First things first.

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Genetic Predisposition to Disease↗

[Tumour angiogenesis and therapy directed at the neovasculature].

BACKGROUND: Tumour angiogenesis and lymphangiogenesis are important new areas of cancer research. In this paper we highlight the central aspects of these processes and describe new therapies directed at the tumour vasculature. We also present some of our own data. MATERIAL AND METHODS: Data from key papers in international journals on tumour angiogenesis and lymphangiogenesis are cited and discussed. RESULTS: Research on tumour angiogenesis and lymphangiogenesis has increased dramatically over the last 30 years. Today, this knowledge is being used to predict the aggressiveness of malignant tumours and to design compounds which can halt the angiogenesis process and affect tumour growth. INTERPRETATION: Insight into how angiogenesis and lymphangiogenesis are regulated in malignant neoplasms is important to the understanding of tumour biology. Currently, numerous clinical trials are conducted with angiogenesis inhibitors; the first completed trials indicate that tumour growth may be retarded in some cancer entities.

Angiogenesis Inhibitors↗

A Monte Carlo study of the impact of the choice of rectum volume definition on estimates of equivalent uniform doses and the volume parameter.

Calculations of normal tissue complication probability (NTCP) values for the rectum are difficult because it is a hollow, non-rigid, organ. Finding the true cumulative dose distribution for a number of treatment fractions requires a CT scan before each treatment fraction. This is labour intensive, and several surrogate distributions have therefore been suggested, such as dose wall histograms, dose surface histograms and histograms for the solid rectum, with and without margins. In this study, a Monte Carlo method is used to investigate the relationships between the cumulative dose distributions based on all treatment fractions and the above-mentioned histograms that are based on one CT scan only, in terms of equivalent uniform dose. Furthermore, the effect of a specific choice of histogram on estimates of the volume parameter of the probit NTCP model was investigated. It was found that the solid rectum and the rectum wall histograms (without margins) gave equivalent uniform doses with an expected value close to the values calculated from the cumulative dose distributions in the rectum wall. With the number of patients available in this study the standard deviations of the estimates of the volume parameter were large, and it was not possible to decide which volume gave the best estimates of the volume parameter, but there were distinct differences in the mean values of the values obtained.

Body Burden↗

Multicenter phase II study of Nordic fluorouracil and folinic acid bolus schedule combined with oxaliplatin as first-line treatment of metastatic colorectal cancer.

PURPOSE: This Nordic multicenter phase II study evaluated the efficacy and safety of oxaliplatin combined with the Nordic bolus schedule of fluorouracil (FU) and folinic acid (FA) as first-line treatment in metastatic colorectal cancer. PATIENTS AND METHODS: Eighty-five patients were treated with oxaliplatin 85 mg/m(2) as a 2-hour infusion on day 1, followed by a 3-minute bolus injection with FU 500 mg/m(2) and, 30 minutes later, by a bolus injection with FA 60 mg/m(2) every second week. The same doses of FU and FA were also given on day 2. RESULTS: Fifty-one of 82 assessable patients achieved a complete (n = 4) or partial (n = 47) response, leading to a response rate of 62% (95% CI, 52% to 72%). Nineteen patients showed stable disease, and 12 patients had progressive disease. Thirty-eight of the 51 responses were radiologically confirmed 8 weeks later (confirmed response rate, 46%; 95% CI, 36% to 58%). The estimated median time to progression was 7.0 months (95% CI, 6.3 to 7.7 months), and the median overall survival was 16.1 months (95% CI, 12.7 to 19.6 months) in the intent-to-treat population. Neutropenia was the main adverse event, with grade 3 to 4 toxicity in 58% of patients. Febrile neutropenia developed in seven patients. Nonhematologic toxicity consisted mainly of neuropathy (grade 3 in 11 patients and grade 2 in another 27 patients). CONCLUSION: Oxaliplatin combined with the bolus Nordic schedule of FU+FA (Nordic FLOX) is a well-tolerated, effective, and feasible bolus schedule as first-line treatment of metastatic colorectal cancer that yields comparable results compared with more complex schedules.

Adult↗

On the use of margins for geometrical uncertainties around the rectum in radiotherapy planning.

BACKGROUND AND PURPOSE: To derive planning organ at risk volume (PRV) margins for the rectum and to analyse the impact of such margins on rectum dose volume histograms (DVHs). PATIENTS AND METHODS: Weekly repeat computer tomography (CT) scans of 19 bladder cancer patients acquired during a conformal radiotherapy course were registered with the corresponding planning CT scans. From these scans, the internal rectal motion was quantified, and the margins that had to be added to the rectum contour in the planning scan to encompass the observed span of rectum motion were determined. These margins were compared to the margins derived using a recent PRV margin recipe. To illustrate the impact of margins on rectum DVHs, the margins were applied in treatment plans of six prostate cancer patients. RESULTS: Altogether 141 CT scans were analysed. On average 24% of the repeat scan rectum volume was displaced outside the planning scan contours, and wall movements of up to 30 mm were observed. Margins of 16 mm anterior and 11 mm posterior encompassed all rectal motion except for the two most displaced rectum walls in each of these directions, in 89% of the patients. Using a recently published statistics-based recipe, margins of 6 mm anterior and 5 mm posterior accounted for the systematic rectum variation, i.e. the average wall position, in 90% of the patients. Adding anterior margin only caused consistent increases (up to 20%) in the fraction of the volume inside the high-dose region (40-70 Gy) compared to the DVH of rectum only. When using both anterior and posterior margins only small shifts (<5%) in the volume fractions were observed. CONCLUSIONS: Rectum PRV margins of 5-6 mm will encompass the systematic component of rectum motion, while margins up to 16 mm are required to also account for most of the random variation. Use of anterior margins only caused large shifts in the DVHs in the clinically significant dose range, while only minor shifts were seen when using both anterior and posterior margins.

Aged↗

Acute morbidity related to treatment volume during 3D-conformal radiation therapy for prostate cancer.

PURPOSE: To investigate the relation between acute toxicity and irradiated volume in the organs at risk during three-dimensional conformal radiation therapy for prostate cancer. METHODS AND MATERIALS: From January to December 2001, we treated 132 prostate cancer patients to a prescribed target dose of 70 Gy. Twenty-six patients (20%) received irradiation to the prostate only (Group P), 86 patients (65%) had field arrangements encompassing the prostate and seminal vesicles (Group PSV) while 20 (15%) received modified pelvic fields (Group MPF). A four-field conformal box technique was used. Acute toxicity according to the RTOG scoring system was prospectively recorded throughout the course of treatment. RESULTS: Overall, radiation was well tolerated with 11%, 16% and 35% Grade 2 gastro-intestinal (GI) toxicity and 19%, 34% and 35% Grade 2 or higher genito-urinary (GU) toxicity in Groups P, PSV and MPF, respectively. In univariate and multivariate analyses treatment group was a significant predictor for Grade 2 or higher acute morbidity. In multivariate logistic regression, the rectum dose-volume histogram parameters were correlated to the incidence of acute Grade 2 GI toxicity, with the fractional volumes receiving more than 37-40 Gy and above 70 Gy showing the statistically strongest correlation. The fractional bladder volume receiving more than 14-27 Gy showed the statistically strongest correlation with acute GU toxicity. CONCLUSIONS: 3D-CRT radiation therapy to 70 Gy for prostate cancer was well tolerated. Only two of the 132 patients in the cohort experienced acute bladder toxicity Grade 3, none had Grade 3 rectal toxicity. Uni- and multivariate analyses indicated that the volume treated was a significant factor for the incidence of Grade 2 or higher acute morbidity.

Acute Disease↗

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↗

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↗

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↗