Memento of the post-mortem.

When the Department of Pathology of the Radboud University Nijmegen Medical Centre in The Netherlands moved from its old to its new premises, the demolition of the marble post-mortem tables was impending, taking with it the Department's (physical) memory. To keep the importance of this memory and of the post-mortem itself on everyone's minds in the new building, the artist Piet Hein Eek was invited to incorporate these post-mortem tables into a work of art. This became a triptych: the three post-mortem tables were stood upright against the wall behind a mounted double sheet of glass, containing screen prints of enlarged microscopic images. The two emblems of pathology-post-mortem tables and double glass slides containing specimens-were thus united into a fascinating work of art: a true memento of the post-mortem, re-embedded in the contemporary world by its design.

Randomized trial of a shared decision-making intervention consisting of trade-offs and individualized treatment information for BRCA1/2 mutation carriers.

PURPOSE: To evaluate a shared decision-making intervention (SDMI) for BRCA1/2 mutation carriers who have to make a choice between screening and prophylactic surgery for breasts and/or ovaries. PATIENTS AND METHODS: The SDMI consisted of two value assessment sessions, using the time trade-off method, followed by individualized treatment information based on (quality-adjusted) life expectancy. After the baseline assessment (2 weeks after a positive DNA test result), women were randomly assigned to the SDMI group (n = 44), receiving the SDMI 2 months after the test result, or to the control group (n = 44). The short- and long-term effects, 3 and 9 months after the test result, were assessed using questionnaires. Data were collected on well-being, treatment choice, and decision-related outcomes. RESULTS: In the short term, the SDMI had no effect. In the long term, with respect to well-being, patients in the SDMI group had less intrusive thoughts (P =.05) and better general health (P =.01) and tended to be less depressed (P =.07). With respect to decision-related outcomes for the breasts, the SDMI group held stronger preferences (P =.02) and agreed more strongly to having weighed the pros and cons (P =.01). No effect was found on treatment choice. In the long term, interaction effects between the SDMI and cancer history were found. The SDMI showed an overall beneficial effect for unaffected women, whereas affected women tended to experience detrimental effects. CONCLUSION: We conclude that the SDMI improved decision making in unaffected BRCA1/2 mutation carriers. Supporting decision making in a systematic way using trade-offs is beneficial for these women.

Impact of BRCA1/2 testing and disclosure of a positive test result on women affected and unaffected with breast or ovarian cancer.

To evaluate the impact of BRCA1/2 testing and disclosure of a positive test result on women affected and unaffected with cancer. Longitudinal cohort study including women affected and unaffected with breast or ovarian cancer testing for a BRCA1/2 mutation. Data on well-being (anxiety, depression, cancer related distress, general health), treatment choice, and decision making about cancer prevention were collected at baseline (1 week after blood sampling; affected n = 192, unaffected n = 176) and at follow-up (2 weeks after disclosure of a positive test result; affected n = 23, unaffected n = 66). Women affected and unaffected with breast or ovarian cancer were compared using univariate statistics. Change over time was examined using repeated measures analysis of variance. With respect to well-being, affected women scored worse at baseline. At follow-up, both affected and unaffected women experienced a decline in well-being, which tended to be stronger in affected women. Women diagnosed with cancer less than 1 year previously tended to report a worse well-being than those diagnosed longer ago. With respect to treatment choice, more affected women intended to obtain prophylactic surgery and valued it higher at both time points. With respect to decision making, affected women had a lower preference for participation in decision making at baseline; no differences were found at follow-up. At follow-up, both affected and unaffected women showed an increase in strength of treatment preference and a decrease in decision uncertainty. Disclosure of a positive test result had a negative impact on well-being. Affected women, especially those who have been recently diagnosed with cancer, experienced the worst well-being and could benefit from psychosocial support.

Randomised trial of a decision aid and its timing for women being tested for a BRCA1/2 mutation.

The aim of the study was to evaluate the impact of a decision aid (DA) and its timing in women being tested for a BRCA1/2 mutation. Women with and without a previous history of cancer were included after blood sampling for genetic testing. The DA consisted of a brochure and video providing information on screening and prophylactic surgery. To evaluate the impact of the DA, women were randomised to the DA group (n=184), receiving the DA 2 weeks after blood sampling, or to the control group (n=184). To evaluate the impact of timing, mutation carriers who had received the DA before the test result (n=47) were compared to mutation carriers who received the DA after the test result (n=42). Data were collected on well-being, treatment choice, decision and information related outcomes. The impact of the DA was measured 4 weeks after blood sampling. The impact of timing was measured 2 weeks after a positive test result. The DA had no impact on well-being. Regarding decision related outcomes, the DA group more frequently considered prophylactic surgery (P=0.02) corroborated with higher valuations (P=0.04). No differences were found for the other decision related outcomes. Regarding information related outcomes, the DA group felt better informed (P=0.00), was more satisfied with the information (P=0.00), and showed more accurate risk perceptions. Timing of the DA had no effect on any of the outcomes. No interactions were found between the DA and history of cancer. In conclusion, women being tested for a BRCA1/2 mutation benefit from the DA on information related outcomes. Because timing had no effect, the DA is considered useful either before or after the test result.

Prophylactic mastectomy or screening in women suspected to have the BRCA1/2 mutation: a prospective pilot study of women's treatment choices and medical and decision-analytic recommendations.

BACKGROUND: Women suspected to have the BRCA1/2 mutation may choose between two management options: breast cancer screening and prophylactic mastectomy (PM). OBJECTIVES: To compare women's treatment choices with medical and decision-analytic recommendations and to explore variables related to the women's choices. METHODS: After provision of information, individual time-tradeoff values for the health outcome "living after PM" were assessed and incorporated into a decision-analytic model, which compared the management options PM and screening with respect to their effects on quality-adjusted life expectancy. RESULTS: Of the 54 women suspected to have the mutation, 51 completed the shared-decision-making procedure. Quality-adjusted life expectancy after PM management was longer for 67% of proven carriers and for 58% of women awaiting the DNA-test result. Twelve proven carriers made definitive treatment choices: eight (67%) chose PM and four (33%) chose screening. All carriers' treatment choices agreed with the normative decision-analytic recommendations. Four (33%) disagreed with the medical recommendations. Of the 36 women awaiting DNA-test results, 32 made hypothetical treatment choices. The agreement between these hypothetical treatment choices and the decision-analytic recommendations was good (78%). Combining data from all 48 women, being married (OR = 14.00, p = 0.006), having children (OR = 4.71, p = 0.02), low desire to participate (OR = 0.14, p = 0.004), high decisional stress (OR = 5.22, p = 0.01), a lower estimate of the "probability of cure for screen-detected breast cancer" (OR = 0.13, p = 0.004), and higher time-tradeoff values for PM (OR = 182, p < 0.0001) made a choice for PM more likely. CONCLUSIONS: The complete agreement between the decision-analytic recommendations and the carriers' choices suggests that women act in accordance with normative decision theory. The disagreement between the carriers' choices and the medical recommendations suggests that women's choices and physicians' recommendations were guided by different arguments. The strong association between time-tradeoff value and treatment choice suggests that the time-tradeoff is a valid method to assess preferences.

Informed consent in palliative radiotherapy: participation of patients and proxies in treatment decisions.

Informed consent is regularly discussed, but little attention has been paid to the daily practice of the patient participation in treatment decisions regarding palliative care. Therefore, an exploratory study was conducted into shared decision making between radiation oncologists and patients and proxies in interviews where decisions regarding palliative radiotherapy have to be made. Interviews of 6 radiation oncologists with 26 outpatients were recorded on audiotape. Each verbal utterance was coded with the aid of the Roter Interaction Analysis System (RIAS). Results indicated that in over 75% of the interviews, patients and proxies were not asked for their opinion regarding treatment decisions. Other treatment options or the option of abstaining from treatment were discussed in 46% of the interviews. In conclusion, in this sample informed consent was not a natural part of the daily practice of palliative radiotherapy. The question remains to what extent informed consent in palliative radiotherapy is realistic.

Evaluation of a shared decision making program for women suspected to have a genetic predisposition to breast cancer: preliminary results.

BACKGROUND: Women suspected to have a genetic predisposition to breast cancer face the difficult choice between regular breast cancer screening and prophylactic mastectomy. The authors developed a shared decision making program (SDMP) to support this decision. OBJECTIVES: To evaluate the SDMP in terms of practicality, beneficial effects, and patient satisfaction. DESIGN: A one-group pretest-posttest design was used. MEASURES: Decision uncertainty, decision burden, subjective knowledge, and risk comprehension were assessed before and after the SDMP. Additional measures were obtained for concepts related to breast cancer concern, desire to participate in the program, satisfaction, program acceptability, and emotional reaction to the program information. RESULTS: Seventy-two women, most of whom were awaiting the genetic test results, participated. Decision uncertainty (effect size d = 0.37) and decision burden (d = 0.41) were reduced by the SDMP. Subjective knowledge (averaged d = 0.94) and risk comprehension were improved. The women were satisfied with the SDMP and found its rationale acceptable. Women who had strong emotional reactions to the information benefited less from the SDMP, whereas women with strong desires to participate in the decision benefited more. CONCLUSIONS: There is a need to give patients more information, especially about prophylactic mastectomy and among gene carriers. Beneficial effects were observed irrespective of whether genetic status was known, suggesting that information concerning treatment options should be made available as soon as DNA testing begins. The better psychological outcomes of women with stronger desires to participate may arise because the desire to participate is characteristic of emotional stability.

Accelerated radiotherapy with carbogen and nicotinamide (ARCON) for laryngeal cancer.

BACKGROUND AND PURPOSE: Tumor hypoxia and tumor cell repopulation are known factors determining radiation response. Accelerated radiotherapy as a method to counteract cellular repopulation was combined with carbogen (95% O2 + 5% CO2) breathing and oral administration of nicotinamide as a means to improve tumor perfusion and oxygenation. The feasibility, toxicity and clinical effectiveness of this approach as a voice-preserving treatment for carcinoma of the larynx was assessed in a prospective study. PATIENTS AND METHODS: Sixty-two patients with stage III-IV laryngeal carcinoma were treated with a schedule of accelerated radiotherapy. The total radiation dose to the primary tumor was 64 Gy and that to the metastatic nodes was 68 Gy delivered in fractions of 2 Gy over 35-37 days. Radiotherapy was combined with carbogen breathing in the initial 11 patients and with both carbogen and nicotinamide administration in the subsequent 51 patients. RESULTS: After a median follow-up of 24 months, the actuarial local control rate at 2 years was 92%. This is higher than any previous report in the literature for this category of patients. Five patients had a local tumor recurrence and underwent laryngectomy. There was one regional recurrence. Including salvage surgery the loco-regional control rate was 100%. Four patients developed distant metastases and died. The actuarial overall survival rate at 2 years was 85%. Toxicity was increased relative to conventional radiotherapy but was considered as acceptable. One patient underwent laryngectomy for radiation-induced cartilage necrosis. CONCLUSION: These preliminary results indicate that advanced laryngeal cancer can be controlled in a high proportion of patients when treated with accelerated radiotherapy combined with carbogen and nicotinamide. This approach offers excellent possibilities for larynx preservation.

Assessment of the time-tradeoff values for prophylactic mastectomy of women with a suspected genetic predisposition to breast cancer.

BACKGROUND: Female carriers of the breast-cancer-susceptibility genes BRCA1 and BRCA2 are at high risk for breast cancer (85%). They face the choice between prophylactic mastectomy (PM) and breast cancer screening. For this treatment choice, a shared-decision-making program was developed. In this program, the time tradeoff (TTO) was used to assess preferences for PM. PURPOSE: Assessment of the feasibility, constant proportional tradeoff, and reliability of using the TTO for this purpose. METHODS: Fifty-four women suspected to carry the BRCA1/2 mutation were provided with comprehensive relevant information. Their preferences for PM were assessed on two occasions. Discrepancies between preferences indicated by the two tests were resolved by testing a third time. The preferences assessed on the last occasion were used for individual decision analyses. In order to test constant proportional tradeoff, the TTO consisted of four items with different numbers of life years. RESULTS: Forty-two women (78%) completed the TTO twice and nine women (17%) performed the test a third time. Three women (5%) completed the TTO only once. The mean TTO value for PM at the last replication was 0.69 (SD=0.30). Violations of constant proportional tradeoff were significant: the largest tradeoffs were recorded for the shortest durations. Pearson's correlation coefficient between the TTO values for the two last sessions was 0.96. CONCLUSION: Assessment of individual preferences by the TTO in this patient group is feasible and reliable. Therefore, the TTO can be used in clinical settings to elicit treatment preferences of women proven or suspected to have a genetic predisposition to breast cancer.

A randomized controlled clinical trial on the efficacy of radiation therapy in the control of subfoveal choroidal neovascularization in age-related macular degeneration: radiation versus observation.

BACKGROUND: The results of several pilot studies concerning radiation therapy for age-related subfoveal choroidal neovascularization (CNV) have been published recently. Although positive treatment results have been described, it is not known whether this therapy alters the natural course of eyes with neovascular age-related macular degeneration (AMD). A randomized controlled clinical trial was conducted in which radiation therapy was compared with observation in patients with subfoveal neovascular AMD. METHODS: Seventy-four patients with a recent drop in central vision due to subfoveal age-related CNV were randomized to either radiation treatment or observation. Patients with either classic, occult or mixed type CNV were included. Eyes in the treatment group received a radiation dose of 24 Gy in four fractions of 6 Gy. Evaluation of data concerning visual acuity (VA) and fluorescein angiography occurred at 3, 6 and 12 months after inclusion. RESULTS: At 12 months of follow-up 52.2% of the observation group versus 32.0% of the irradiation group had lost 3 or more lines of VA (P = 0.03, log rank test). More severe visual decline, 6 lines or more, was observed in 40.9% of the observation versus 8.8% in the irradiation group (P = 0.002 using log rank test). At 12 months 39.6% of the observation group and 20.0% of the treatment group had VA of less than 0.1 (P = 0.08, log rank test). The size of the CNV membrane doubled in 25.2% of eyes in the observation group versus 20.0% in the treatment group at least 12 months (P = 0.5, log rank test). No side effects were observed. CONCLUSION: Preservation of VA was significantly better in the treatment group compared with the control group at 12 months. Nevertheless we noted a drop in central vision of 3 or more lines in a substantial proportion of the treatment group. Radiation therapy does not prevent visual loss in all patients with age-related subfoveal CNV, and whether the treatment benefit at 12 months will persist has to be awaited.

A review on family history of breast cancer: screening and counseling proposals for women with familial (non-hereditary) breast cancer.

With the aim to specify screening recommendations for women with familial (non-hereditary) breast cancer (FBC) we analysed 59 studies using quantitative methods of pooling. The pooled relative risk (RR) and cumulative probability were used to estimate breast cancer risk. The RRs for women with a family history of breast cancer in a first-degree relative was 2.03 (95% CI 1.09-2.22). The highest RR is observed for women with a family history and atypical hyperplasia in their breast biopsy specimen (RR = 10.87, 95% CI 6.05-19.69). A high cumulative probability before the age of 50 was only found for women with a combination of two risk factors: a family history and atypical hyperplasia, namely 19% (95% CI 11-33%). The cumulative probabilities of women aged 50 to 70 years who have a family history were between 11% (95% CI 9-13%, a family history in combination with age at first birth before 22 years) and 53% (95% CI 35-75%, a family history in combination with atypical hyperplasia). These high risks suggest that women over 50 years of age who have a family history of FBC have to be actively encouraged to participate in a screening program consisting of a biannual palpation by a specialist, an annual mammogram and a monthly self-control. Yearly screening is recommended for women under 50 years of age who have a family history and atypical hyperplasia. These recommendations remain valid until the effectiveness of such screening programs is assessed.

Administration of nicotinamide during a five- to seven-week course of radiotherapy: pharmacokinetics, tolerance, and compliance.

BACKGROUND AND PURPOSE: Nicotinamide was administered daily as a liquid formulation to head and neck cancer patients receiving a 5- to 7-week course of radiotherapy. The pharmacokinetics, compliance, and tolerance of this drug formulation were studied. MATERIALS AND METHODS: Blood samples were drawn and nicotinamide levels determined in 40 head and neck cancer patients. On the first treatment day serial samples were obtained followed by daily samples at the time of irradiation during the first and last full weeks of the treatment. Side-effects of nicotinamide were monitored. RESULTS: In all patients peak concentrations greater than 700 nmol/ml could be obtained 0.25-3 h (mean 0.83 +/- 0.73 h) after drug intake. During the first week of treatment plasma levels at the time of irradiation were adequate in 82% of the samples. This decreased to 59% in the last week of treatment which can be partly attributed to reduced compliance. The most important side-effect of nicotinamide was nausea with or without vomiting occurring in 65% of the patients. Severe side-effects were associated with high plasma concentrations over subsequent days. Tolerance improved after a 25% reduction of dose in six of seven patients but plasma levels at the time of irradiation fell below 700 nmol/ml in four out of six of these patients. CONCLUSIONS: Peak plasma concentrations above the 700 nmol/ml level were obtained in all patients but these concentrations could not be reproduced during the entire course of the treatment in a significant portion of the subjects. Side-effects of nicotinamide are associated with plasma concentrations and tolerance can be improved by a moderate reduction of dose.

[Vascularization and perfusion of tumors as target in cancer therapy]. / Vascularisatie en doorbloeding van tumoren als doelwit voor kankertherapie.

Many tumours depend on the formation of an own vascular system to support progressive tumour growth. This is accomplished through induction of vessel growth from pre-existing vessels, a process called neo-angiogenesis. Therefore, inhibiting neo-angiogenesis and modulating tumour perfusion constitute attractive possibilities for tumour therapy, combined, of course, with treatment aimed at the tumour cells themselves. By now many angiogenesis inhibitors have been developed, but their use is mostly still experimental. They inhibit endothelial proliferation and migration (fumagillin derivates, angiostatin, suramin) or prevent proteolytic degeneration of the extracellular matrix by products of the tumour (metalloproteinase inhibitors). Improving tumour oxygenation and perfusion by carbogen inhalation and nicotinamide or vasoactive agents (flunarizine, verapamil, nicotinamide) enhances the effects of radiotherapy and improves delivery of chemotherapeutic agents to the tumour. Research is currently in progress into the efficacy of accelerated radiotherapy in combination with carbogen inhalation and administration of nicotinamide in tumours of the head and neck, bladder, bronchi and brain.

Infrastructure for radiotherapy in The Netherlands: development from 1970 to 2010.

In 1993 the radiotherapy advisory committee of the Dutch Health Council published its report on the developments of infrastructure for radiotherapy in The Netherlands during the last 10 years and the prognosis for future needs until 2010. Based on demographic trends, the expected incidence of cancer, the role of radiotherapy in the treatment of cancer, and the workload assessment in a model department, two scenarios are presented for the development of infrastructure. According to the committee, the Quality Scenario would be the most appropriate.

Visual acuity and scar size in eyes with age-related subfoveal choroidal neovascular lesions, 30 months after radiation therapy.

PURPOSE: In a study to determine the effectiveness of ionizing radiation on the deterioration of visual acuity (VA) due to choroidal neovascularisation (CNV) the affected eyes of 10 patients were treated with a total dose of 24 Gy (6 Gy fractions). A special lens-sparing technique was used to avoid cataract development. During 30 months of follow-up the visual acuity (VA) and scar size (SS) of the treated eyes and fellow eyes of all 10 patients were evaluated. RESULTS: After 30 months of follow-up 5 eyes showed a stable VA and fluorescein angiogram (FA) appearance. Concerning 4 out of 5 eyes with progressive disease, the 4 eyes treated with radiation therapy had better VA and smaller SS as compared with the untreated fellow eyes with exudative AMD. CONCLUSIONS: The results suggest that 24 Gy either stabilizes or delays the deleterious effects of CNV on the visual acuity. Until now no late side effects have been observed.

Radiotherapy with carbogen breathing and nicotinamide in head and neck cancer: feasibility and toxicity.

The feasibility and early toxicity of radiotherapy with carbogen breathing and nicotinamide was tested in 74 head and neck cancer patients. Forty patients with laryngeal and hypopharyngeal tumors were treated with an accelerated schedule combined with carbogen alone (16) or with carbogen and nicotinamide (24). Thirty-four patients with far advanced unresectable tumors of the oral cavity and oropharynx received conventional radiotherapy with carbogen [16] or with carbogen and nicotinamide (18). Some enhancement of skin reaction was observed with nicotinamide but this remained well within limits of tolerance. With the accelerated regimen there was increased severity of mucosal damage expressed as confluent mucositis in 95% of patients which required healing times of 3-4 months in four patients. Eventually restoration of the mucosal lining was complete in all cases. Nausea and vomiting are the most frequent side effects of nicotinamide and were reported by 60% and 36% of the subjects, respectively. In 26% this was reason to discontinue drug intake. Severe renal dysfunction was associated with nicotinamide intake in two patients of this study and in one other patient who presented later. It is our conclusion that radiotherapy combined with carbogen and nicotinamide is a safe treatment with manageable side effects. We recommend not to give nicotinamide concomitantly with nephrotoxic medication or to patients who have impaired renal function. Preliminary tumor control rates are encouraging and clinical testing will be continued.

Personality traits of women with breast cancer: before and after diagnosis.

The aim of this study was to investigate the extent to which the diagnosis of breast cancer influences the self-assessment of personality traits by patients. In 1989 and 1990, all female inhabitants of Nijmegen aged 43 years and over were invited to participate in a population screening for breast cancer and were asked to complete a personality questionnaire. During 1989-1992, 25 women who were diagnosed as having breast cancer were psychologically assessed for a second time 1 1/2 years after diagnosis. A control group of 822 healthy women also completed the questionnaire twice. A statistically significant decrease in scores on three scales (Rationality, Emotional Expression-out, and Emotional-Control) was reported by the patient group compared to the control group.

Radiation therapy for age-related subfoveal choroidal neovascular membranes. A pilot study.

In this pilot study the effect of radiation therapy on subfoveal CNV membranes associated with age-related macular degeneration was evaluated. Four groups of 10 patients were treated with external beam radiotherapy (16 MV photons) on an area of 1 cm2 (macular region) using a lens-sparing technique and total dose of 8 to 24 Gy. The first group received 8 Gy in a single fraction. In this group only 30% had a stable visual acuity and a stable FA after 18 months follow-up. In 50% of patients in group 2 (12 Gy) and 40% of patients in group 3 (18 Gy) the visual acuity and FA appearance remained stable after 18 months of follow-up. In the last group (24 Gy) 80% of patients had a stable visual acuity and FA appearance after 12 months follow-up. Comparison of these findings with the natural history data of subfoveal age-related CNV, suggests a beneficial effect of radiation therapy with a total dose of 12 Gy or more on the progression of CNV membranes.

Radiation therapy for subfoveal choroidal neovascular membranes in age-related macular degeneration. A pilot study.

BACKGROUND: The natural course of the visual acuity of age-related subfoveal choroidal neovascularisation (CNV) membranes is poor. Laser photocoagulation of subfoveal CNV is recommended if the patient is willing to accept a large decrease in visual acuity immediately after treatment. A large proportion of patients with subfoveal CNV do not meet the Macular Photocoagulation Study Group (MPS) guidelines for laser photocoagulation. The fact that so few patients meet these criteria makes further research into new treatment techniques warranted. Ionising radiation may prevent the proliferation of endothelial cells of newly formed subretinal capillaries and may induce obliteration of the aberrant new vessels. METHODS: In this study, the effect of radiation therapy on subfoveal CNV membranes was evaluated. Four groups of ten patients were treated with external beam radiotherapy (16-MV photons) on an area of 1 cm2 (macular region) using a lens-sparing technique and total doses of 8-24 Gy. The first group received 8 Gy in one fraction. The second, third and fourth groups received 12 Gy in 2 fractions, 18 Gy in three fractions and 24 Gy in four fractions respectively. The studied parameters included best-corrected visual acuity and membrane size and leakage on the fluorescein angiogram. We included 17 occult and 23 classic CNV membranes as defined by the MPS, with a duration of less than 5 weeks at presentation. Complete ophthalmic examination including fluorescein angiography was performed before and 3, 12 and 18 months after radiation treatment. We analysed the angiogram using a standard overprojection sheet. The results concerning the visual acuity and fluorescein angiography (FA) were compared with the extensively published, natural course data. RESULTS: The first group (including three cases of occult CNV) received 8 Gy in a single fraction. In this group only four of ten patients had stable visual acuity and stable FA appearance after 21 months follow-up. The visual acuity and FA remained stable after 13.6 months follow-up in seven of the patients in group 2 (12 Gy in two fractions, four occult CNV). The third group (18 Gy in three fractions, seven occult CNV) contained six patients with stable visual acuity, although two of them had CNV deterioration on the FA (11.1 months follow-up). In the last group (24 Gy in four fractions, three occult CNV), with a short follow-up of 5.6 months, eight patients had stable visual acuity and FA appearance. We did not note any regression of the CNV membrane on the angiogram. The visual acuity in groups 2, 3 and 4 decreased to 0.1 or worse in only three cases, three cases and one case respectively after at least 6 months follow-up. CONCLUSION: Comparison of these findings with the natural history data of subfoveal age-related CNV suggests a beneficial effect of radiation therapy with a total dose of 12 Gy or more on the progression of CNV. To date no negative side effects have been observed.

Risk attitude in gambles with years of life: empirical support for prospect theory.

According to prospect theory, risk attitude changes depending on whether a prospect is perceived as a gain or a loss relative to a reference or aspiration level. To investigate risk attitude with respect to years of life, the authors elicited utilities at two occasions by the certainty equivalent method from 30 women from the general population. The respondents gave certainty equivalents to gambles with years of life. The gambles were two-outcome gambles with equal probabilities to experience each outcome. A shift from a risk-seeking towards a risk-averse attitude was observed with increasing expected value of the gambles. For each individual, the averaged responses over the two replications were fitted with an s-shaped logistic curve that showed an excellent fit (r2 > or = 0.97) for all respondents. The aspiration level of survival can be derived from this function and was negatively correlated with age (r = -0.43, p < 0.025). The data are consistent with prospect theory and may explain why patients opt for risky treatments, since most of the respondents were risk-seeking in the short term.