PurposeTo describe recall of fertility-related consultations and cryopreservation and to examine reproductive goals and reproduction post-treatment in long-term survivors of adolescent and young... Show morePurposeTo describe recall of fertility-related consultations and cryopreservation and to examine reproductive goals and reproduction post-treatment in long-term survivors of adolescent and young adult (AYA) (age, 18-39 years) cancer.MethodsThis study included n = 1457 male and n = 2112 female long-term survivors (Mage = 43-45 years; 5-22 years from diagnosis) who provided self-report. Clinical data were supplied by the Netherlands Cancer Registry.ResultsMost male survivors (72.7%) recalled fertility-related consultations and 22.6% completed sperm cryopreservation. Younger age (OR = 2.8; 95%CI [2.2-3.6]), not having children (OR = 5.0; 95%CI [3.2-7.7]), testicular cancer or lymphoma/leukemia (OR = 2.8/2.5 relative to "others"), and more intense treatments (OR = 1.5; 95%CI [1.1-2.0]) were associated with higher cryopreservation rates. Time since diagnosis had no effect. Of men who cryopreserved, 12.1% utilized assisted reproductive technologies (ART). Most men (88.5%) felt their diagnosis did not affect their reproductive goals, but 7.6% wanted no (additional) children due to cancer. Half of female survivors (55.4%; n = 1171) recalled fertility-related consultations. Rates of cryopreservation were very low (3.6%), but increased after 2013 when oocyte cryopreservation became non-experimental. Of women who cryopreserved, 13.2% successfully utilized ART. Most women (74.8%) experienced no effects of cancer on reproductive goals, but 17.8% wanted no (additional) children due to cancer.ConclusionsCryopreservation in men varied by patient/clinical factors and was very low in women, but data of more recently treated females are needed. Utilizing cryopreserved material through ART was rare, which questions its cost-effectiveness, but it may enhance survivors' well-being.Implications for Cancer SurvivorsThe extent to which cryopreservation positively affects survivors' well-being remains to be tested. Moreover, effects of cancer on reproductive goals require further attention, especially in women who refrain from having children due to cancer. Show less
Bootsma, T.I.; Wal, D. van de; Vlooswijk, C.; Roos, D.C.; Drabbe, C.; Tissier, R.; ... ; Husson, O. 2024
PurposeAdolescent and young adult cancer survivors (AYAs) are at increased risk of long-term and late effects, and experience unmet needs, impacting their health-related quality of life (HRQoL). In... Show morePurposeAdolescent and young adult cancer survivors (AYAs) are at increased risk of long-term and late effects, and experience unmet needs, impacting their health-related quality of life (HRQoL). In order to provide and optimize supportive care and targeted interventions for this unique population, it is important to study HRQoL factors' interconnectedness on a population level. Therefore, this network analysis was performed with the aim to explore the interconnectedness between HRQoL factors, in the analysis described as nodes, among long-term AYAs.MethodsThis population-based cohort study used cross-sectional survey data of long-term AYAs, who were identified by the Netherlands Cancer Registry (NCR). Participants completed a one-time survey (SURVAYA study), including the EORTC survivorship questionnaire (QLQ-SURV111) to assess their long-term HRQoL outcomes and sociodemographic characteristics. The NCR provided the clinical data. Descriptive statistics and a network analysis, including network clustering, were performed.ResultsIn total, 3596 AYAs (on average 12.4 years post diagnosis) were included in our network analysis. The network was proven stable and reliable and, in total, four clusters were identified, including a worriment, daily functioning, psychological, and sexual cluster. Negative health outlook, part of the worriment cluster, was the node with the highest strength and its partial correlation with health distress was significantly different from all other partial correlations.ConclusionThis study shows the results of a stable and reliable network analysis based on HRQoL data of long-term AYAs, and identified nodes, correlations, and clusters that could be intervened on to improve the HRQoL outcomes of AYAs. Show less
Meer, D.J. van der; Zevenbergen, S.; Vlooswijk, C.; Bijlsma, R.M.; Kaal, S.E.J.; Kerst, J.M.; ... ; Husson, O. 2023
Background: Adolescent and young adult cancer survivors (AYAs, aged 18-39 years at first diagnosis) have a higher second cancer risk. Accelerated aging is hypothesized as underlying mechanism and... Show moreBackground: Adolescent and young adult cancer survivors (AYAs, aged 18-39 years at first diagnosis) have a higher second cancer risk. Accelerated aging is hypothesized as underlying mechanism and has been described clinically by 6 indicators; fatigue, low quality of sleep, low mood, lack of motivation, subjective memory complaints, and poor exercise tolerance. Using patient-reported outcomes, we aimed to identify clusters of accelerated aging among AYA cancer survivors and to investigate their association with second cancer development.Patients and Methods: Patient, tumor, and treatment data were obtained from the Netherlands Cancer Registry. Patient-reported clinical indicators and second cancer data were obtained from the SURVivors (5-20 years) of cancer in AYAs (SURVAYA) questionnaire study between 1999 and 2015. Latent class and multivariable logistic regression analyses were performed.Results: In total, n = 3734 AYA survivors with known second cancer status (n = 278 [7.4%] second cancers) were included. Four latent clusters were identified and named based on their clinical indicator features; (1) high accelerated aging (31.3%), (2) intermediate accelerated aging without poor exercise tolerance (15.1%), (3) intermediate accelerated aging without lack of motivation (27.4%), and (4) low accelerated aging (26.2%). AYAs in the high accelerated aging cluster were more likely to have second cancer (odds ratio: 1.6; 95% CI, 1.1-2.3) compared to the low accelerated aging cluster.Conclusion: AYAs with a higher burden of accelerated aging were more likely to develop a second cancer. Validation of the clinical indicators and how to best capture them is needed to improve (early) detection of AYAs at high risk of developing second cancer. Show less
Background: Despite growing (inter)national awareness and appreciation, age-specific care is still not always self-evident and accepted as standard of care for adolescent and young adult (AYA)... Show moreBackground: Despite growing (inter)national awareness and appreciation, age-specific care is still not always self-evident and accepted as standard of care for adolescent and young adult (AYA) cancer patients. It is unknown whether long-term AYA cancer survivors have missed age-specific care, and if so, which survivors missed it and regarding which topics.Methods: The Netherlands Cancer Registry (NCR) identified all long-term AYA cancer survivors (aged 18-39 years at initial cancer diagnosis, 5-20 years past diagnosis) in the Netherlands, who were invited to participate in a population-based, observational, cross-sectional questionnaire study (SURVAYA study), including questions on care needs.Results: In total, 3.989 AYAs participated (35.3% response rate). One-third of them had a need for age-specific care (33.5%), 41.2% had no need and 25.3% did not know whether they had a need. Those who had a need for age-specific care were significantly more often female, higher educated, diagnosed at a younger age, and treated with chemotherapy, radiotherapy or hormone therapy. Most frequent topics were disease and treatment (29.7%), emotions (24.1%), friends (22.6%), family and children (15.6%), fertility and pregnancy (14.8%), work and reintegration (10.5%), care not tailored (13.8%), and overarching care and life (27.7%). Palliative care (0.0%), spirituality (0.2%), death (0.7%), complementary care (0.7%), and late effects (1.3%) were mentioned least.Conclusions: A substantial proportion of long-term AYA cancer survivors showed a need for age-specific care, varying by sociodemographic and clinical factors, on a wide variety of topics, which could be targeted to improve current AYA care services. Show less
Burgers, V.W.G.; Bent, M.J. van den; Dirven, L.; Lalisang, R.I.; Tromp, J.M.; Compter, A.; ... ; Husson, O. 2022
Introduction: Increasingly more adolescent and young adult (AYA, aged 18-39 years) patients with an uncertain and/or poor cancer prognosis (UPCP) are gaining life-years because of novel treatments... Show moreIntroduction: Increasingly more adolescent and young adult (AYA, aged 18-39 years) patients with an uncertain and/or poor cancer prognosis (UPCP) are gaining life-years because of novel treatments or refinement of established therapies, and sometimes even face the prospect of long-term disease control. This study aims to examine the challenges of AYAs with a UPCP in daily life to inform the development of AYA care programs. Methods: Semi-structured in-depth interviews were conducted among AYAs with a UPCP. Since we expected differences in experiences between three AYA subgroups, we interviewed patients of these subgroups (1): traditional survivors (2), low-grade glioma survivors, and (3) new survivors. Interviews were analyzed using elements of grounded theory. AYA patients were actively involved as research partners. Results: In total 46 AYAs with UPCP participated and shared their challenges in daily life. They were on average 33.4 years old (age range 23-44) and most of them were women (63%). The most common tumor types were low-grade gliomas (16), sarcomas (7), breast cancers (6), and lung cancers (6). We identified five primary themes: (1) feeling inferior to previous self and others (e.g. feeling useless, who wants me in a relationship), (2) feeling of being alone (e.g. lonely thoughts, nobody really gets me), (3) ongoing confrontation (e.g. it is always there, own decline), (4) grief about life (e.g. grief about life I did not get, grief about old life), and (5) loss of control over the future (e.g. not able to make future plans, waiting for growth). Although all of the challenges were identified in the three AYA subgroups, the perceived intensity of the challenges differed slightly between the subgroups. Discussion: AYAs living with a UPCP experience challenges associated to their sense of altered identity, their position in the social network, and the future uncertainties. This study highlights the importance to recognize and acknowledge the unique challenges of this group. To provide age-specific care, it is important to embed acceptance and commitment therapy and AYA peer support within the healthcare system and other care programs to support AYAs to live well with their disease. Show less
Saris, L.M.H.; Vlooswijk, C.; Kaal, S.E.J.; Nuver, J.; Bijlsma, R.M.; Hulle, T. van der; ... ; Husson, O. 2022
Simple Summary: Adolescent and young adult (AYA) cancer survivors diagnosed with cancer between ages 18-39 years often experience negative body changes, such as scars, amputation, hair loss,... Show moreSimple Summary: Adolescent and young adult (AYA) cancer survivors diagnosed with cancer between ages 18-39 years often experience negative body changes, such as scars, amputation, hair loss, disfigurement, body weight changes, skin buns, and physical movement limitations. A negative body image could have negative implications for the self-esteem, self-identity, and social relationships of AYAs. Despite the possible long-term effects of cancer on body image, within the AYA literature, limited studies focus on AYA cancer survivors in a quantitative way. Therefore, the aim of our population-based cross-sectional study was to examine the prevalence, and association of a negative body image with sociodemographic, clinical, and psychosocial factors, among AYA survivors 5-20 years after diagnosis. Raising awareness and integrating supportive care for those who experience a negative body image into standard AYA survivorship care is warranted. Future longitudinal research could help to identify when and how this support for AYA survivors can be best utilized. Adolescent and young adult (AYA) cancer survivors (18-39 years at diagnosis) often experience negative body changes such as scars, amputation, and disfigurement. Understanding which factors influence body image among AYA survivors can improve age-specific care in the future. Therefore, we aim to examine the prevalence, and association of a negative body image with sociodemographic, clinical, and psychosocial factors, among AYA cancer survivors (5-20 years after diagnosis). A population-based cross-sectional cohort study was conducted among AYA survivors (5-20 years after diagnosis) registered within the Netherlands Cancer Registry (NCR) (SURVAYA-study). Body image was examined via the EORTC QLQ-C30 and QLQ-SURV100. Multivariable logistic regression models were used. Among 3735 AYA survivors who responded, 14.5% (range: 2.6-44.2%), experienced a negative body image. Specifically, AYAs who are female, have a higher Body Mass Index (BMI) or tumor stage, diagnosed with breast cancer, cancer of the female genitalia, or germ cell tumors, treated with chemotherapy, using more maladaptive coping strategies, feeling sexually unattractive, and having lower scores of health-related Quality of Life (HRQoL), were more likely to experience a negative body image. Raising awareness and integrating supportive care for those who experience a negative body image into standard AYA survivorship care is warranted. Future research could help to identify when and how this support for AYA survivors can be best utilized. Show less
Vlooswijk, C.; Poll-Franse, L.V. van de; Janssen, S.H.M.; Derksen, E.; Reuvers, M.J.P.; Bijlsma, R.; ... ; Husson, O. 2022
Background: Participation of Adolescents and Young Adults with cancer (AYAs: 18-39 years at time of diagnosis) in patient-reported outcome studies is warranted given the limited knowledge of (long... Show moreBackground: Participation of Adolescents and Young Adults with cancer (AYAs: 18-39 years at time of diagnosis) in patient-reported outcome studies is warranted given the limited knowledge of (long-term) physical and psychosocial health outcomes. We examined the representativeness of AYAs participating in the study, to observe the impact of various invitation methods on response rates and reasons for non-participation. Methods: A population-based, cross-sectional cohort study was performed among long-term (5-20 years) AYA cancer survivors. All participants were invited using various methods to fill in a questionnaire on their health outcomes, including enclosing a paper version of the questionnaire, and sending a reminder. Those who did not respond received a postcard in which they were asked to provide a reason for non-participation. Results: In total, 4.010 AYAs (response 36%) participated. Females, AYAs with a higher socio-economic status (SES), diagnosed more than 10 years ago, diagnosed with a central nervous system tumor, sarcoma, a lymphoid malignancy, stage III, or treated with systemic chemotherapy were more likely to participate. Including a paper questionnaire increased the response rate by 5% and sending a reminder by 13%. AYAs who did not participate were either not interested (47%) or did want to be reminded of their cancer (31%). Conclusions: Study participation was significantly lower among specific subgroups of AYA cancer survivors. Higher response rates were achieved when a paper questionnaire was included, and reminders were sent. To increase representativeness of future AYA study samples, recruitment strategies could focus on integrating patient-reported outcomes in clinical practice and involving AYA patients to promote participation in research. Show less
Kester, L.; Seinstra, D.; Rossum, A.G.J. van; Vennin, C.; Hoogstraat, M.; Velden, D. van der; ... ; Rheenen, J. van 2022
Purpose: Extensive work in preclinical models has shown that microenvironmental cells influence many aspects of cancer cell behavior, including metastatic potential and their sensitivity to... Show morePurpose: Extensive work in preclinical models has shown that microenvironmental cells influence many aspects of cancer cell behavior, including metastatic potential and their sensitivity to therapeutics. In the human setting, this behavior is mainly correlated with the presence of immune cells. Here, in addition to T cells, B cells, macrophages, and mast cells, we identified the relevance of nonimmune cell types for breast cancer survival and therapy benefit, including fibroblasts, myoepithelial cells, muscle cells, endothelial cells, and seven distinct epithelial cell types.Experimental Design: Using single-cell sequencing data, we generated reference profiles for all these cell types. We used these reference profiles in deconvolution algorithms to optimally detangle the cellular composition of more than 3,500 primary breast tumors of patients that were enrolled in the SCAN-B and MATADOR clinical trials, and for which bulk mRNA sequencing data were available.Results: This large data set enables us to identify and subsequently validate the cellular composition of miaoenvironments that distinguish differential survival and treatment benefit for different treatment regimens in patients with primary breast cancer. In addition to immune cells, we have identified that survival and therapy benefit are characterized by various contributions of distinct epithelial cell types.Conclusions: From our study, we conclude that differential survival and therapy benefit of patients with breast cancer are characterized by distinct microenvironments that include specific populations of immune and epithelial cells. Show less
Background The onset of the COVID-19 pandemic forced the Dutch national screening program to a halt and increased the burden on health care services, necessitating the introduction of specific... Show moreBackground The onset of the COVID-19 pandemic forced the Dutch national screening program to a halt and increased the burden on health care services, necessitating the introduction of specific breast cancer treatment recommendations from week 12 of 2020. We aimed to investigate the impact of COVID-19 on the diagnosis, stage and initial treatment of breast cancer. Methods Women included in the Netherlands Cancer Registry and diagnosed during four periods in weeks 2-17 of 2020 were compared with reference data from 2018/2019 (averaged). Weekly incidence was calculated by age group and tumor stage. The number of women receiving initial treatment within 3 months of diagnosis was calculated by period, initial treatment, age, and stage. Initial treatment, stratified by tumor behavior (ductal carcinoma in situ [DCIS] or invasive), was analyzed by logistic regression and adjusted for age, socioeconomic status, stage, subtype, and region. Factors influencing time to treatment were analyzed by Cox regression. Results Incidence declined across all age groups and tumor stages (except stage IV) from 2018/2019 to 2020, particularly for DCIS and stage I disease (p < 0.05). DCIS was less likely to be treated within 3 months (odds ratio [OR](wks2-8): 2.04, ORwks9-11: 2.18). Invasive tumors were less likely to be treated initially by mastectomy with immediate reconstruction (ORwks12-13: 0.52) or by breast conserving surgery (ORwks14-17: 0.75). Chemotherapy was less likely for tumors diagnosed in the beginning of the study period (ORwks9-11: 0.59, ORwks12-13: 0.66), but more likely for those diagnosed at the end (ORwks14-17: 1.31). Primary hormonal treatment was more common (ORwks2-8: 1.23, ORwks9-11: 1.92, ORwks12-13: 3.01). Only women diagnosed in weeks 2-8 of 2020 experienced treatment delays. Conclusion The incidence of breast cancer fell in early 2020, and treatment approaches adapted rapidly. Clarification is needed on how this has affected stage migration and outcomes. Show less
Background Many cancer patients use additional herbs or supplements in combination with their anti-cancer therapy. Green tea-active ingredient epigallocatechin-3-gallate (EGCG)-is one of the most... Show moreBackground Many cancer patients use additional herbs or supplements in combination with their anti-cancer therapy. Green tea-active ingredient epigallocatechin-3-gallate (EGCG)-is one of the most commonly used dietary supplements among breast cancer patients. EGCG may alter the metabolism of tamoxifen. Therefore, the aim of this study was to investigate the influence of green tea supplements on the pharmacokinetics of endoxifen; the most relevant active metabolite of tamoxifen. Methods In this single-center, randomized cross-over trial, effects of green tea capsules on endoxifen levels were evaluated. Patients treated with tamoxifen for at least 3 months were eligible for this study. After inclusion, patients were consecutively treated with tamoxifen monotherapy for 28 days and in combination with green tea supplements (1 g twice daily; containing 300 mg EGCG) for 14 days (or vice versa). Blood samples were collected on the last day of monotherapy or combination therapy. Area under the curve (AUC(0-24h)), maximum concentration (C-max) and minimum concentration (C-trough) were obtained from individual plasma concentration-time curves. Results No difference was found in geometric mean endoxifen AUC(0-24h)in the period with green tea versus tamoxifen monotherapy (- 0.4%; 95% CI - 8.6 to 8.5%;p = 0.92). Furthermore, no differences inC(max)(- 2.8%; - 10.6 to 5.6%;p = 0.47) norC(trough)(1.2%; - 7.3 to 10.5%;p = 0.77) were found. Moreover, no severe toxicity was reported during the whole study period. Conclusions This study demonstrated the absence of a pharmacokinetic interaction between green tea supplements and tamoxifen. Therefore, the use of green tea by patients with tamoxifen does not have to be discouraged. Show less
Delayed time to chemotherapy (TTC) is associated with decreased outcomes of breast cancer patients. Recently, studies suggested that the association might be subtype-dependent and that TTC within... Show moreDelayed time to chemotherapy (TTC) is associated with decreased outcomes of breast cancer patients. Recently, studies suggested that the association might be subtype-dependent and that TTC within 30 days should be warranted in patients with triple-negative breast cancer (TNBC). The aim of the current study is to determine if TTC beyond 30 days is associated with reduced 10-year overall survival in TNBC patients. We identified all TNBC patients diagnosed between 2006 and 2014 who received adjuvant chemotherapy in the Netherlands. We distinguished between breast-conserving surgery (BCS) vs. mastectomy given the difference in preoperative characteristics and outcomes. The association was estimated with hazard ratios (HRs) using propensity-score matched Cox proportional hazard analyses. In total, 3,016 patients were included. In matched patients who underwent BCS (n = 904), 10-year overall survival was favorable for patients with TTC within 30 days (84.4% vs. 76.9%, p = 0.001). Patients with TTC beyond 30 days were more likely than those with TTC within 30 days to die within 10 years after surgery (HR 1.69 (95% CI 1.22-2.34), p = 0.002). In matched patients who underwent mastectomy (n = 1,568), there was no difference in 10 years overall survival between those with TTC within or beyond 30 days (74.5% vs. 74.7%, p = 0.716), nor an increased risk of death for those with TTC beyond 30 days (HR 1.04 (95% CI 0.84-1.28), p = 0.716). Initiation of adjuvant chemotherapy beyond 30 days is associated with decreased 10 years overall survival in TNBC patients who underwent BCS. Therefore, timelier initiation of chemotherapy in TNBC patients undergoing BCS seems warranted. Show less
Jonge, M.M. de; Ruano, D.; Eijk, R. van; Stoep, N. van der; Nielsen, M.; Wijnen, J.T.; ... ; Asperen, C.J. van 2018
