Danish heritable retinoblastoma survivors' perspectives on reproductive choices: "It's important for me, not to pass on this condition".

Despite reporting an overall normal life, survivors of heritable retinoblastoma face numerous physical and psychosocial issues. In particular, reproductive decision-making is often complex and difficult. This study aims to examine survivors' reflections on passing on heritable retinoblastoma to their children, how survivors approach their reproductive choices, and how the healthcare system can optimize counseling and support. Semi-structured interviews with Danish adult survivors of heritable retinoblastoma were qualitatively analyzed to explore their experiences. Participants were recruited from the Retinoblastoma Survivorship Clinic, Aarhus University Hospital, Denmark. Thematic data analysis was conducted followed by a condensing process specifically for the subthemes relating to reproductive choices. A common subtheme for all participants was a strong wish to avoid passing on retinoblastoma to their children. The participants emphasized the various medical, practical, emotional, and moral issues impacting their final reproductive choice in the process of family planning to conceive a child unaffected by retinoblastoma. Some had no option other than to conceive naturally and hope for an unaffected baby; while others weighed the pros and cons of choosing natural conception with prenatal testing and then considering termination of pregnancy (in case of an affected fetus) versus choosing fertility treatment with preimplantation genetic testing to achieve an unaffected pregnancy. Several participants underlined the complexity of their decisions, and also expressed feelings of guilt, both toward their affected child, and guilt for putting their partner through many difficult decisions and obstacles due to their genetic condition. Our findings demonstrate how one family-planning decision is not unequivocally "better" or easier than another. Healthcare professionals must provide the necessary information and tools to support the individual's unique decision-making process. Survivors' autonomy and individual needs, as well as the numerous and diverse aspects of heritable retinoblastoma, should be carefully considered.

Genetic testing in adult survivors of retinoblastoma in Denmark: A study of the experience and impact of genetic testing many years after initial diagnosis.

BACKGROUND: Survivors with heritable retinoblastoma (RB) face a high risk for second primary cancer and RB in their children. Knowledge of heredity can support second cancer surveillance, convey reproductive options or early diagnosis of RB in their offspring. Currently, all newly diagnosed Danish patients with RB are offered genetic testing, as opposed to a minority of survivors diagnosed before available DNA testing. OBJECTIVE: To examine RB survivors' response to unsolicited contact, uptake of genetic testing, and RB1 variant detection rate, and to qualitatively evaluate the experience and overall impact of genetic testing for heritable RB. METHODS: Genetically untested adult RB survivors were invited to receive genetic counseling, undergo genetic testing for heritable RB and complete an eye examination. The number of responses, uptake of genetic testing and genetic results are descriptively reported. Additionally, responding survivors participated in a qualitative interview study of the perceived impact of genetic testing. Interviews were audio-recorded, transcribed verbatim and thematically analyzed. RESULTS: Among invited RB survivors, 58% responded. Of these, 88% opted for genetic counseling and genetic testing. A diagnosis of heritable RB was established in 23% of RB survivors. Interestingly, all of these survivors were unilaterally affected. Analysis of data from the interviews revealed three recurring themes regarding the impact of genetic counseling and testing several years after initial diagnosis: 'Risk of what?', 'Knowledge is important' and 'Impact of the result'. The possible risk ofsecond cancer and RB in their children was new knowledge for several participants; however, in general, the participants appreciated receiving genetic information and certainty about heredity. Accordingly, the impact of genetic counseling and testing was perceived in a positive way. CONCLUSION: Overall, RB survivors valued the opportunity to receive genetic counseling and undergo genetic testing many years after diagnosis. Responding RB survivors appreciated the invitation to test, felt well-informed and described little decisional conflict regarding their decision-making, valuing the genetic information and certainty. Heritable RB was confirmed in 23% of the previously untested RB survivors. These individuals emphasized the value of knowing and being proactive regarding both reproduction and cancer risk.

Living with heritable retinoblastoma and the perceived role of regular follow-up at a retinoblastoma survivorship clinic: 'That is exactly what I have been missing'.

OBJECTIVE: To explore living with heritable retinoblastoma, specifically survivors' perceived role of regular follow-up at a retinoblastoma survivorship clinic. METHODS AND ANALYSIS: Adult survivors of heritable retinoblastoma were recruited from the Retinoblastoma Survivorship Clinic, Aarhus University Hospital. Ten survivors participated in individual explorative, semistructured interviews. Thematic data analysis was conducted. RESULTS: Five key themes relating to vision, social life, family, second cancer risk and the healthcare system were identified. Subthemes relating to the Retinoblastoma Survivorship Clinic included the retinoblastoma coordinator, cancer risk, psychosocial support and genetic knowledge. The retinoblastoma-related physical and psychosocial issues influenced survivors' everyday living; however, the opportunity to live a normal life varied considerably, with the majority experiencing no major limitations. The need for specialised management and a coordinator was emphasised to be the main value of the Retinoblastoma Survivorship Clinic. CONCLUSION: Despite reporting an overall normal life and no major limitations in daily living activities, our data confirm that heritable retinoblastoma impacts several aspects of daily living. Uniquely, this study demonstrates that the main value of the Retinoblastoma Survivorship Clinic was a specialised contact person and coordinator in the healthcare system, providing continuous and necessary management and guidance after retinoblastoma treatment, and for all aspects of health related to heritable retinoblastoma. The needs of heritable retinoblastoma survivors are complex and extensive, and the specific role of the healthcare system to support survivorship should be prioritised, specialised and multidisciplinary.

Incidence and Mortality of Second Primary Cancers in Danish Patients With Retinoblastoma, 1943-2013.

Importance: In heritable retinoblastoma, there is a significantly increased risk of second primary cancers (SPCs). Improved knowledge about the incidence and influence of heritability and treatment is important during therapy for patients with retinoblastoma. Objective: To assess the incidence of SPC in patients diagnosed with retinoblastoma in Denmark from 1943 to 2013 with a focus on heritability and the association of external radiotherapy with mortality. Design, Setting, and Participants: In this retrospective cohort study, data were extracted from the Danish Ocular Oncology Group Database containing complete data on all patients diagnosed with retinoblastoma , and obtained from the Danish Cancer Registry, which includes information on all patients with cancer from 1943 to December 31, 2013. Data analysis was conducted from December 1, 2017, to October 1, 2019. Data on 323 patients were included. Exposures: Heritability and retinoblastoma treatment. Main Outcomes and Measures: Standardized incidence rate, excess absolute risk, cumulative incidence of SPC, and mortality from SPC. Association of heritability and treatment with outcomes was estimated. Results: Of the 323 patients included in the analysis, 181 were men (56%), 133 had heritable retinoblastoma (41%), and 190 had nonheritable retinoblastoma (59%). The median age at diagnosis of SPC was 32.4 (interquartile range, 15.4-43.9) years in patients with heritable retinoblastoma and 38.6 (interquartile range, 20.5-49.4) years in those with nonheritable retinoblastoma. Twenty-five SPCs were identified in patients with heritable retinoblastoma vs 14 in patients with nonheritable retinoblastoma. Standardized incidence rate (SIR) of SPC in patients with heritable retinoblastoma was 11.39 (95% CI, 7.37-16.81) with an excess absolute risk of 70 cases per 10 000 person-years; the highest SIRs were for sarcoma (181.13; 95% CI, 98.94-303.92) and malignant melanoma (26.78; 95% CI, 9.78-58.30). The SIR for SPC in patients with nonheritable retinoblastoma was 1.52 (95% CI, 0.81-2.60). The cumulative incidence of SPCs at age 60 years was significantly higher in patients with heritable retinoblastoma (51%) compared with those with nonheritable retinoblastoma (13%) (P < .001) (hazard ratio, 5.0; 95% CI, 2.5-10.3). No significant differences were identified in overall risk of SPC in patients with heritable retinoblastoma treated with 3 different modalities: external radiotherapy, plaque (but no external) radiotherapy, and enucleation only, but an increased proportion of sarcomas was noted in the irradiated field. Mortality due to SPC was also higher in survivors of heritable retinoblastoma compared with those with nonheritable retinoblastoma (cumulative mortality, 34% vs 12% at age 60 years; P = .03). Conclusions and Relevance: The findings of this study suggest that the incidence and mortality associated with SPC were significantly higher in patients with heritable retinoblastoma vs patients with nonheritable retinoblastoma. The largest increases in risk were noted for sarcoma and malignant melanoma. External radiotherapy did not appear to increase the risk. These findings are relevant when treating patients with retinoblastoma to manage the risk for SPC.

First use of antidepressant medication in male partners of women with breast cancer in Denmark from 1998 to 2011.

OBJECTIVE: A diagnosis of breast cancer disrupts the life of the patient, but also the partner may experience adverse psychological effects. We examined partners' risk for first use of antidepressant medication, as a proxy for pharmacologically treated depression. METHODS: By linkage of national registers, we identified 1 420 592 depression-free men living with a cancer-free female partner in 1998 to 2011. During follow-up, breast cancer was diagnosed in female partners of 26 256 men. In Poisson regression models, we estimated the rate ratios for first use of antidepressant medication compared to partners of breast cancer-free women. Cox regression analyses examined associations between exposed partners' sociodemographic characteristics, somatic comorbidity, death of female partner, and first use of antidepressant medication. RESULTS: Male partners of women with breast cancer had an increased rate ratio of 1.08 (95% CI, 1.03-1.13) for first use of antidepressant medication compared to the background population, corresponding to excess absolute risk of 12 cases per 10 000 person-years. This increased risk persisted throughout 14 years of follow-up. Higher age, shorter education, somatic comorbidity, and death of female partner were associated with increased risk among men whose partner had breast cancer. CONCLUSION: The modest, but long term, increased risk for first use of antidepressant medication calls for attention by health care professionals to symptoms of depression among partners of breast cancer patients.

Predictors of continuous tobacco smoking in a clinical cohort study of Danish laryngeal cancer patients smoking before treated with radiotherapy.

BACKGROUND: Many cancer patients who are smokers when starting cancer therapy continue smoking despite evidence of tobacco smoking as a risk factor for poor treatment response and secondary primary cancers. Small samples and inconsistent results in previous studies warrant further research to identify predictors of being a continuous smoker during and after radiotherapy. MATERIAL AND METHODS: In the clinical database of the Danish Head and Neck Cancer Group (DAHANCA), we identified 1455 patients diagnosed with laryngeal cancer between 2000 and 2010, who were all smokers at date of diagnosis and treated with primary radiotherapy. Information on the socio-economic characteristics of the study cohort was obtained from Statistics Denmark the year prior to diagnosis. Logistic regression analyses were applied. RESULTS: In the cohort of laryngeal cancer patients smoking before starting radiotherapy, 50% still smoked one year after radiotherapy similar to the percentage of smokers during treatment. Being younger than 60 years (OR 1.39, 95% CI 1.00-1.91), commenced smoking before the age of 15 (OR 1.77, 95% CI 1.32-2.38), having a poor WHO Performance status (OR 3.09, 95% CI 1.71-5.61), low income (OR 2.21, 95% CI 1.23-3.98) and living alone (OR 1.56, 95% CI 1.13-2.14) were associated with increased risk of continuous smoking during treatment. Similar findings were found two months and one year after radiotherapy, however, no association with living alone (OR 1.08, 95% CI 0.73-1.59) at the one-year follow-up. Tumor stage and the average number of cigarettes smoked per day before radiotherapy were not associated with being a continuous smoker. CONCLUSION: Younger patients, who had an early smoking initiation, a poor performance status, low income and lived alone, were most likely to continue smoking. Continuous smoking was not related to the extent of disease.