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Contains fulltext : 305391.pdf (Publisher’s version ) (Open Access), BACKGROUND: This study compares the characteristics, referral and treatment patterns and overall survival (OS) of gastrointestinal stromal tumor (GIST) patients treated in reference and non-reference centers in the Netherlands. PATIENTS AND METHODS: This retrospective cohort study on patients diagnosed between 2016 and 2019, utilises data from the Netherlands Cancer Registry and the Dutch Nationwide Pathology Database. Patients were categorized into two groups: patients diagnosed in or referred to reference centers and patients diagnosed in non-reference centers without referral. RESULTS: This study included 1,550 GIST patients with a median age of 67.0 in reference and 68.0 years in non-reference centers. Eighty-seven per cent of patients were diagnosed in non-reference centers, of which 36.5% (493/1,352) were referred to a reference center. Referral rates were higher for high-risk (62.2% [74/119]) and metastatic patients (67.2% [90/134]). Mutation analysis was performed in 96.9% and 87.6% of these cases in reference and in non-reference centers (p < 0.01), respectively. Systemic therapy was given in reference centers versus non-reference in 89.5% versus 82.0% (p < 0.01) of high-risk and in 94.1% versus 65.9% (p < 0.01) of metastatic patients, respectively. The proportion of positive resection margins and tumor rupture did not differ between reference and non-reference centers. Median OS was not reached. CONCLUSION: A substantial amount of metastatic GIST patients in non-reference centers did not receive systemic treatment. This might be due to valid reasons. However, optimisation of the referral strategy of GIST patients in the Netherlands could benefit patients. Further research is needed to explore reasons for not starting systemic treatment in metastatic GIST patients.

Item does not contain fulltext, PURPOSE: Watchful waiting (WW) can be considered for patients with metastatic clear-cell renal cell carcinoma (mccRCC) with good or intermediate prognosis, especially those with <2 International Metastatic RCC Database Consortium criteria and ≤2 metastatic sites [referred to as watch and wait ("W&W") criteria]. The IMaging PAtients for Cancer drug SelecTion-Renal Cell Carcinoma study objective was to assess the predictive value of [18F]FDG PET/CT and [89Zr]Zr-DFO-girentuximab PET/CT for WW duration in patients with mccRCC. EXPERIMENTAL DESIGN: Between February 2015 and March 2018, 48 patients were enrolled, including 40 evaluable patients with good (n = 14) and intermediate (n = 26) prognosis. Baseline contrast-enhanced CT, [18F]FDG and [89Zr]Zr-DFO-girentuximab PET/CT were performed. Primary endpoint was the time to disease progression warranting systemic treatment. Maximum standardized uptake values (SUVmax) were measured using lesions on CT images coregistered to PET/CT. High and low uptake groups were defined on the basis of median geometric mean SUVmax of RECIST-measurable lesions across patients. RESULTS: The median WW time was 16.1 months [95% confidence interval (CI): 9.0-31.7]. The median WW period was shorter in patients with high [18F]FDG tumor uptake than those with low uptake (9.0 vs. 36.2 months; HR, 5.6; 95% CI: 2.4-14.7; P < 0.001). Patients with high [89Zr]Zr-DFO-girentuximab tumor uptake had a median WW period of 9.3 versus 21.3 months with low uptake (HR, 1.7; 95% CI: 0.9-3.3; P = 0.13). Patients with "W&W criteria" had a longer median WW period of 21.3 compared with patients without: 9.3 months (HR, 1.9; 95% CI: 0.9-3.9; Pone-sided = 0.034). Adding [18F]FDG uptake to the "W&W criteria" improved the prediction of WW duration (P < 0.001); whereas [89Zr]Zr-DFO-girentuximab did not (P = 0.53). CONCLUSIONS: In patients with good- or intermediate-risk mccRCC, low [18F]FDG uptake is associated with prolonged WW. This study shows the predictive value of

01 januari 2023, Item does not contain fulltext, BACKGROUND: Adolescents and young adults (AYAs) diagnosed with cancer fulfill their cancer-related information needs often via the Internet. Healthcare professionals (HCPs) have a crucial role in guiding patients in finding appropriate online information and eHealth sources, a role that is often overlooked. Misperceptions of AYAs' needs by HCPs may lead to suboptimal guidance. We aimed to examine the extent to which AYAs' online information and eHealth needs corresponded with HCPs' perceptions of these needs. METHODS: Two cross-sectional online surveys (AYAs, n = 299; HCP, n = 80) on online information and eHealth needs were conducted. HCPs provided indications of their perceptions of AYA's needs. RESULTS: AYAs reported significantly more online information needs compared with HCPs' perceptions regarding: survival rates (AYA = 69%, HCP = 35%, p < 0.001), treatment guidelines (AYA = 65%, HCP = 41%, p < 0.001), return of cancer (AYA = 76%, HCP = 59%, p = 0.004), "what can I do myself" (AYA = 68%, HCP = 54%, p = 0.029), and metastases (AYA = 64%, HCP = 50%, p = 0.040). Significantly more unmet eHealth needs were reported by AYAs compared with HCPs relating to access to own test results (AYA = 25, HCP = 0%, p < 0.001), request tests (AYA = 30%, HCP = 7%, p < 0.001), medical information (AYA = 22%, HCP = 0%, p = 0.001), e-consult with nurses (AYA = 30%, HCP = 10%, p < 0.001), e-consult with physicians (AYA = 38%, HCP = 13%, p = 0.001), and request prescriptions (AYA = 33%, HCP = 21%, p = 0.009). CONCLUSION: AYAs' online information and eHealth needs are partially discrepant with the impression HCPs have, which could result in insufficient guidance related to AYAs' needs. AYAs and HCPs should get guidance regarding where to find optimal information in a language they understand. This may contribute to AYAs' access, understanding, and satisfaction regarding online information and eHealth.

Contains fulltext : 290144.pdf (Publisher’s version ) (Open Access)

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Item does not contain fulltext, BACKGROUND: Sarcomas account for almost 11% of all cancers in adolescents and young adults (AYAs; 18-39 years). AYAs are increasingly recognized as a distinct oncological age group with its own psychosocial challenges and biological characteristics. Social functioning has been shown to be one of the most severely affected domains of health-related quality of life in AYA cancer survivors. This study aims to identify AYA sarcoma survivors with impaired social functioning (ISF) and determine clinical and psychosocial factors associated with ISF. METHODS: AYAs from the population-based cross-sectional sarcoma survivorship study (SURVSARC) were included (n = 176). ISF was determined according to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 social functioning scale, and age- and sex-matched norm data were used as reference. RESULTS: The median time since diagnosis was 6.2 years (range, 1.8-11.2). More than one-quarter (28%) of AYA sarcoma survivors experienced ISF. Older age, higher tumor stage, comorbidities, lower experienced social support, uncertainty in relationships, feeling less attractive, sexual inactivity, unemployment, and financial difficulties were associated with ISF. In a multivariable analysis, unemployment (OR, 3.719; 95% CI, 1.261-10.967) and having to make lifestyle changes because of financial problems caused by one's physical condition or medical treatment (OR, 3.394; 95% CI, 1.118-10.300) were associated with ISF; better experienced social support was associated with non-ISF (OR, 0.739; 95% CI, 0.570-0.957). CONCLUSION: More than one-quarter of AYA sarcoma survivors experience ISF long after diagnosis. These results emphasize the importance of follow-up care that is not only disease-oriented but also focuses on the psychological and social domains. PLAIN LANGUAGE SUMMARY: Sarcomas account for almost 11% of all cancers in adolescents and young adults (AYAs; 18-39 years). The AYA group is increasi

Item does not contain fulltext, INTRODUCTION: The development of desmoid fibromatosis (DF) is associated with pregnancy. The current treatment consensus recommends active surveillance (AS). However, data in pregnancy-associated DF is scarce and it is uncertain whether AS is the best management strategy for this DF-subgroup. The aim of this study was to describe demographic, tumor, obstetric, treatment characteristics and treatment outcome in pregnancy-associated DF. METHODS: Female DF patients who were 18-50 years old at time of diagnosis (2000-2020) and had a history (≤5 years) of pregnancy at time of diagnosis were included. RESULTS: Overall, 62 patients were included. The most common locations were abdominal wall (74%), pelvis (10%) and extremities (10%). Mutational analysis was conducted in 31 patients of which 94% had CTNNB1-mutations. Ten patients (16%) were diagnosed during pregnancy, while the remainder were diagnosed after pregnancy with a median time from delivery to diagnosis of 19 months (1-60). The frontline management was AS in 38 patients (61%) of whom 12 (33%) developed progressive disease and surgery in 23 patients (37%). In total, 30 patients underwent surgery and five had local recurrence (17%). Positive resection margins were no prognostic factor. Nine patients received systemic treatment in second- or third-line. CONCLUSIONS: Pregnancy-associated DF generally has an indolent behavior, where our results underscore the difficulty of establishing a clear definition of this entity. This study shows that AS should be the frontline management strategy for pregnancy-associated DF. When active treatment is indicated, surgery is a good option with low recurrence rates, even with positive (R1) resection margins.

Contains fulltext : 296505.pdf (Publisher’s version ) (Open Access), The health-related quality of life (HRQoL) among long-term Adolescent and Young Adult Cancer Survivors (AYACS) and an age- and sex-matched normative population was examined. Although the HRQoL of AYACS was worse compared to the normative population before and during the COVID-19 pandemic, the scores of AYACS improved over time in contrast to the normative population. Presumably, AYACS are used to adjusting their lives to stressful life events. Furthermore, the lockdown may have been beneficial for AYACS who face difficulties fully participating in society due to the impact of cancer. AYACS who encounter HRQoL issues could benefit from support interventions to empower them and build resilience.

01 juni 2023, Contains fulltext : 294556.pdf (Publisher’s version ) (Open Access), BACKGROUND: Desmoid-type fibromatosis (DTF) has a highly variable clinical course with varying intensity of symptoms. The objectives of this study were to identify subgroups of DTF patients based on physical symptom burden and to compare symptom burden subgroups on health-related quality of life (HRQoL) and healthcare use (univariate and multivariate). METHODS: Desmoid-type fibromatosis patients from the United Kingdom and the Netherlands received cross-sectional questionnaires on HRQoL (EORTC QLQ-C30), DTF-specific HRQoL (DTF-QoL) and healthcare utilisation. Latent class cluster analysis was performed to identify subgroups based on patients' symptom burden using EORTC QLQ-C30 and DTF-QoL physical symptom items. Multivariate linear and logistic regression analyses were conducted to examine associations of symptom burden with HRQoL and healthcare utilisation, respectively. RESULTS: Among 235 DTF patients, four symptom burden clusters were identified, with low symptom burden (24%), intermediate symptom burden-low pain (20%), intermediate symptom burden-high pain (25%) and high symptom burden (31%). DTF patients with high symptom burden had clinically relevant lower HRQoL scores compared to patients with low and intermediate symptom burden (p < 0.001) and reported more general and DTF-related visits to their general practitioner compared to the low symptom burden cluster (p < 0.01). In the multivariate analyses, symptom burden was independently associated with both HRQoL and healthcare utilisation. CONCLUSIONS: This study identified four distinct subgroups of DTF patients based on their level of symptom burden, with a considerable number of patients being highly symptomatic. Knowledge of the level of symptom burden DTF patients experience can help to identify patients at risk of poorer outcomes and tailor supportive care to the individual needs of DTF patients.

01 juni 2023, Contains fulltext : 294535.pdf (Publisher’s version ) (Open Access), 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) 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.

Contains fulltext : 300113.pdf (Publisher’s version ) (Open Access), BACKGROUND: There are two main coping styles regarding information seeking under medical threat; monitoring (information-seeking) and blunting (information-avoiding). The aim of this study is to (1) determine factors associated with a monitoring or blunting coping style in gastro-intestinal stromal tumour (GIST) patients and (2) investigate its association with psychological distress, cancer-related concerns, health-related quality of life and satisfaction with healthcare. METHODS: In a cross-sectional study, Dutch GIST patients completed the shortened version of the Threatening Medical Situations Inventory to determine their coping style, the Hospital Anxiety and Depression Scale, Cancer Worry Scale, EORTC QLQ-C30 and part of the EORTC QLQ-INFO25. RESULTS: A total of 307 patients were classified as blunters (n = 175, 57%) or monitors (n = 132, 43%). Coping style was not associated with tumour or treatment variables, but being a female (OR 2.5; 95%CI 1.5-4.1; p= <.001) and higher educated (OR 5.5; 95%CI 2.5-11.9, p= <.001) were associated with higher odds of being a monitor. Monitors scored significantly lower on emotional functioning (mean = 86.8 vs mean = 90.9, p=.044), which is considered a trivial difference, more often experienced severe fear of cancer recurrence or progression (53.0% vs 37.7%, p=.007), and had more concerns about dying from GIST in the future (60.6% vs 47.4%, p=.025). Compared to blunters, monitors were less satisfied with the received healthcare and information, and would have liked to receive more information. CONCLUSION: GIST patients with a monitoring coping style experience a higher emotional burden. Additionally, monitors exhibit a greater need for information. Although this need for information could potentially result in fears and concerns, recognising it may also create an opening for tailored communication and information., 01 december 2023

Contains fulltext : 247659.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 247465.pdf (Publisher’s version ) (Open Access)

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Item does not contain fulltext, OBJECTIVE: The aim of the study is to assess the effect of perioperative chemotherapy (CTX) in patients with grade II-III extremity soft tissue sarcoma (eSTS) on overall survival (OS) and evaluate whether the PERSARC prediction tool could identify patients with eSTS more likely to benefit from CTX. METHODS: Patients (18-70 years) with primary high-grade eSTS surgically treated with curative intent were included in the retrospective cohort study. The effect of any perioperative CTX and anthracycline + ifosfamide (AI)-based CTX on OS was investigated in three PERSARC-risk groups (high/intermediate/low). The PERSARC-risk groups were defined by the 33% and 66% quantile of the predicted 5-year OS of the study population equal to a 5-year OS of 65.8% and 79.8%, respectively. The effect of CTX on OS was investigated with weighted Kaplan-Meier curves and multivariable Cox models with an interaction between risk group and CTX. RESULTS: This study included 5683 patients. The weighted Kaplan-Meier curves did not demonstrate a beneficial effect of any CTX and AI-based CTX on OS in the overall population. However, in the high PERSARC-risk group the 5-year OS of AI-based CTX was significantly better than no CTX (69.8% vs 59.0%, respectively, p = 0.004) (HR 0.66, 95%CI 0.53-0.83). CONCLUSIONS: This study demonstrated a beneficial effect of AI-based CTX on OS in a selected group of high-risk patients with an absolute survival benefit of 11% as stratified by the PERSARC prediction tool. However, no beneficial effect of CTX on OS was found in the overall population of patients with primary high-grade eSTS younger than 70 years.

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Radboud University, 31 oktober 2022, Promotor : Graaf, W.T.A. van der Co-promotores : Desar, I.M.E., Husson, O., Item does not contain fulltext

Item does not contain fulltext, BACKGROUND: Sex differences in cancer have gained attention in recent years. The role of sex as a prognostic factor in gastrointestinal stromal tumours (GIST) has not been well established. The aim of this research was to elucidate potential sex differences in GIST patients and the influence of sex on disease-specific survival (DSS). METHODS: A review of the literature was carried out to obtain an overview of all literature with sex as a covariate on GIST survival analyses. Furthermore, in the Dutch GIST Registry, GIST characteristics between males and females were compared and the influence of sex on DSS was analysed. RESULTS: A total of 118 articles from the review of the literature met our selection criteria; 58% of the articles found no sex difference in survival and 42% did find a sex difference. All differences favoured female patients, although there was substantial overlap of individual patients in the various reported groups. The Dutch GIST Registry cohort consisted of 1425 patients (46% female). Compared with female patients, male patients had larger tumours (mean 9.0 cm versus 7.9 cm) and higher mitotic rates (34.4% versus 28.0% >5 mitoses/5 mm(2)). GIST in males was more often metastasized at diagnosis (21.3% versus 13.7%) and incurable (38.5% versus 31.0%). Male patients less often received surgery of the primary tumour (71.7% versus 78.9%), but did experience more tumour ruptures (18.2% versus 13.3%). Male patients had a worse DSS than females. This was not statistically significant when corrected for differences in GIST characteristics. CONCLUSIONS: In case of sex differences in GIST in the literature, male patients have a worse outcome. In our Dutch GIST cohort a similar finding was made, but sex was shown not to be an independent factor. Male patients more often had aggressive GISTs, with larger tumours, higher mitotic rates, more tumour ruptures, and metastases, which could explain the sex differences in DSS.

Item does not contain fulltext, BACKGROUND: Increasingly, social media is being recognized as a potential resource for patient-generated health data, for example, for pharmacovigilance. Although the representativeness of the web-based patient population is often noted as a concern, studies in this field are limited. OBJECTIVE: This study aimed to investigate the sample bias of patient-centered social media in Dutch patients with gastrointestinal stromal tumor (GIST). METHODS: A population-based survey was conducted in the Netherlands among 328 patients with GIST diagnosed 2-13 years ago to investigate their digital communication use with fellow patients. A logistic regression analysis was used to analyze clinical and demographic differences between forum users and nonusers. RESULTS: Overall, 17.9% (59/328) of survey respondents reported having contact with fellow patients via social media. Moreover, 78% (46/59) of forum users made use of GIST patient forums. We found no statistically significant differences for age, sex, socioeconomic status, and time since diagnosis between forum users (n=46) and nonusers (n=273). Patient forum users did differ significantly in (self-reported) treatment phase from nonusers (P=.001). Of the 46 forum users, only 2 (4%) were cured and not being monitored; 3 (7%) were on adjuvant, curative treatment; 19 (41%) were being monitored after adjuvant treatment; and 22 (48%) were on palliative treatment. In contrast, of the 273 patients who did not use disease-specific forums to communicate with fellow patients, 56 (20.5%) were cured and not being monitored, 31 (11.3%) were on curative treatment, 139 (50.9%) were being monitored after treatment, and 42 (15.3%) were on palliative treatment. The odds of being on a patient forum were 2.8 times as high for a patient who is being monitored compared with a patient that is considered cured. The odds of being on a patient forum were 1.9 times as high for patients who were on curative (adjuvant) treatment and 10 times as high for pa

Contains fulltext : 252028.pdf (Publisher’s version ) (Open Access), BACKGROUND: Research in sarcomas has historically been the domain of scientists and clinicians attempting to understand the disease to develop effective treatments. This traditional approach of placing scientific rigor before the patient's reality is changing. This evolution is reflected in the growth of patient-centered organizations and patient advocacy groups that seek to meaningfully integrate patients into the research process. The aims of this study are to identify the unanswered questions regarding sarcomas (including gastrointestinal stromal tumors and desmoid fibromatosis) from patient, carer, and clinical perspectives and examine how patients and carers want to be involved in sarcoma research. METHODS: The Patient-Powered Research Network of Sarcoma Patients EuroNet set up a Priority Setting Partnership (PSP) in collaboration with stakeholders from the sarcoma research field. This PSP is largely based on the James Lind Alliance methodology. RESULTS: In total, 264 sarcoma patients (73%) and carers (27%) from all over the world participated in the online survey and covered the full spectrum of sarcomas. The topics mentioned were labeled in accordance with the Common Scientific Outline of the International Cancer Research Partnership and lists for potential research topics, advocacy topics, and requests for information were constructed. With regard to patient and carer involvement, 64% were very willing to be actively involved and mainly in the following areas: sharing perspectives, discussing patient-clinician interactions, and attending research meetings. CONCLUSIONS: The first results of this sarcoma PSP identified important research questions, but also important topics for patient advocacy groups and further improvement of information materials. Sarcoma patients and carers have a strong wish to be involved in multiple aspects of sarcoma research. The next phase will identify the top 10 research priorities per tumor type. These priorities will provide guid

Contains fulltext : 253634.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 285445.pdf (Publisher’s version ) (Open Access)

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Contains fulltext : 252033.pdf (Publisher’s version ) (Open Access), PURPOSE: Treatment with the tyrosine kinase inhibitor (TKI) imatinib in patients with gastrointestinal stromal tumours (GIST) causes symptoms that could negatively impact health-related quality of life (HRQoL). Treatment-related symptoms are usually clinician-reported and little is known about patient reports. We used survey and online patient forum data to investigate (1) prevalence of patient-reported symptoms; (2) coverage of symptoms mentioned on the forum by existing HRQoL questionnaires; and (3) priorities of prevalent symptoms in HRQoL assessment. METHODS: In the cross-sectional population-based survey study, Dutch GIST patients completed items from the EORTC QLQ-C30 and Symptom-Based Questionnaire (SBQ). In the forum study, machine learning algorithms were used to extract TKI side-effects from English messages on an international online forum for GIST patients. Prevalence of symptoms related to imatinib treatment in both sources was calculated and exploratively compared. RESULTS: Fatigue and muscle pain or cramps were reported most frequently. Seven out of 10 most reported symptoms (i.e. fatigue, muscle pain or cramps, facial swelling, joint pain, skin problems, diarrhoea, and oedema) overlapped between the two sources. Alopecia was frequently mentioned on the forum, but not in the survey. Four out of 10 most reported symptoms on the online forum are covered by the EORTC QLQ-C30. The EORTC-SBQ and EORTC Item Library cover 9 and 10 symptoms, respectively. CONCLUSION: This first overview of patient-reported imatinib-related symptoms from two data sources helps to determine coverage of items in existing questionnaires, and prioritize HRQoL issues. Combining cancer-generic instruments with treatment-specific item lists will improve future HRQoL assessment in care and research in GIST patients using TKI.

Contains fulltext : 252034.pdf (Publisher’s version ) (Open Access), Desmoplastic small round cell tumors (DSRCTs), Ewing sarcoma (ES), and alveolar and embryonal rhabdomyosarcoma (ARMS and ERMS) are malignant sarcomas typically occurring at young age, with a poor prognosis in the metastatic setting. New treatment options are necessary. Src family kinase inhibitor dasatinib single-agent treatment has been investigated in a phase 2 study in patients with advanced sarcomas including ES and RMS but failed as a single agent in these subtypes. Since previous studies demonstrated high FAK and Src activities in RMS and ES tissue and cell lines, and dasatinib treatment was shown to upregulate activated FAK, we hypothesized that FAK-Src combination treatment could potentially be an interesting treatment option for these tumor types. We examined the effects of targeting the FAK-Src complex by addressing (p)FAK and (p)Src expressions in tumor sections of DSRCT (n = 13), ES (n = 68), ARMS (n = 21), and ERMS (n = 39) and by determining the antitumor effects of single and combined treatment with FAK inhibitor defactinib and multikinase (Abl/SFK) inhibitor dasatinib in vitro on cell lines of each subtype. In vivo effects were assessed in DSRCT and ERMS models. Concurrent pFAK and pSrc expressions (H-score >50) were observed in DSRCT (67%), ES (6%), ARMS (35%), and ERMS (19%) samples. Defactinib treatment decreased pFAK expression and reduced cell viability in all subtypes. Dasatinib treatment decreased pSrc expression and cell viability in each subtype. Combination treatment led to a complete reduction in pFAK and pSrc in each cell line and showed enhanced cell viability reduction, drug synergy, DNA damage induction, and a trend toward higher apoptosis induction in DSRCT, ERMS, and ARMS but not in ES cells. These promising in vitro results unfortunately do not translate into promising in vivo results as we did not observe a significant effect on tumor volume in vivo, and the combination did not show superior effects compared to dasatinib single-age

Contains fulltext : 253507.pdf (Publisher’s version ) (Open Access), Simple Summary: An emerging group of advanced cancer patients are living long term on systemic treatment. However, studies examining the psychosocial impact of this prolonged cancer treatment trajectory are scarce. This scoping review summarizes findings on these psychosocial issues, as well as the terminology used to refer to these patients. Prominent psychosocial outcomes included uncertainty, anxiety, and fear of disease progression or death, hope, loss and worries about loved ones and changes in social life. These themes were not extensively investigated in research using validated psychological questionnaires. More quantitative research in this area should be conducted to further understand these psychological constructs. A large variety of terms used to refer to the patient group was observed, which calls for a uniform definition to better address this specific patient group in research and in practice. By identifying key themes and gaps in the literature, directions for future research and clinical practice can be provided. Abstract: (1) Background: Studies examining the psychosocial impact of living long term on systemic treatment in advanced cancer patients are scarce. This scoping review aimed to answer the research question "What has been reported about psychosocial factors among patients living with advanced cancer receiving life-long systemic treatment?", by synthesizing psychosocial data, and evaluating the terminology used to address these patients; (2) Methods: This scoping review was conducted following the five stages of the framework of Arksey and O'Malley (2005); (3) Results: 141 articles published between 2000 and 2021 (69% after 2015) were included. A large variety of terms referring to the patient group was observed. Synthesizing qualitative studies identified ongoing uncertainty, anxiety and fear of disease progression or death, hope in treatment results and new treatment options, loss in several aspects of life, and worries about the impact

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Contains fulltext : 251577.pdf (Publisher’s version ) (Open Access), Desmoid-type fibromatosis (DTF) is a rare, soft-tissue tumour. These tumours do not metastasize, but their local aggressive tumour growth and unpredictable behaviour can have a significant impact on health-related quality of life (HRQoL). Little is known about which DTF patients are particularly affected by an impaired HRQoL. The objectives of this study were to assess HRQoL among different groups of DTF patients and to investigate which socio-demographic and clinical characteristics were associated with DTF-specific HRQoL. A cross-sectional study was conducted among DTF patients from the United Kingdom and the Netherlands. HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), accompanied by the DTF-QoL to assess DTF-specific HRQoL. The scores were compared amongst subgroups, based on the socio-demographic and clinical characteristics of DTF patients. Multiple linear regression analyses with a backward elimination were conducted to identify the factors associated with DTF-specific HRQoL. A total of 235 DTF patients completed the questionnaires. Female patients, patients with more than two comorbidities, or patients who received treatment other than only active surveillance (AS) or surgery scored significantly worse on the subscales of both the EORTC QLQ-C30 and DTF-QoL. Patients that were ≥ 40 years scored significantly worse on the physical functioning scale of the EORTC QLQ-C30, while younger patients (18-39 years) scored significantly worse on several DTF-QoL subscales. Differences in the DTF-QoL subscales were found for tumour location, time since diagnosis and the presence of recurrent disease. Furthermore, treatments other than AS or surgery only, female sex, younger age and the presence of comorbidities were most frequently associated with worse scores on the DTF-QoL subscales. This study showed that (DTF-specific) HRQoL differs between groups of DTF patients. Awareness o

Gastrointestinal stromal tumours (GISTs) are malignant mesenchymal tumours with a variable clinical behaviour, marked by differentiation towards the interstitial cells of Cajal.1 GISTs belong to the family of soft tissue sarcomas (STSs) but are treated separately due to their peculiar histogenesis, clinical behaviour and specific therapy. This European Society for Medical Oncology (ESMO)–European Reference Network for Rare Adult Solid Cancers (EURACAN)–European Reference Network for Genetic Tumour Risk Syndromes (GENTURIS) Clinical Practice Guideline (CPG) will cover GISTs while other STSs are covered in the ESMO–EURACAN–European Reference Network for Paediatric Oncology (ERN PaedCan)–GENTURIS STS CPG.

Item does not contain fulltext, PURPOSE: Angiosarcoma (AS) is a rare vasoformative sarcoma, with poor overall survival and a high need for novel treatment options. Clinically, AS consists of different subtypes, including AS related to previous UV exposure (UV AS) which could indicate susceptibility to DNA damage repair inhibition. We, therefore, investigated the presence of biomarkers PARP1 (poly(ADP-ribose)polymerase-1) and Schlafen-11 (SLFN11) in UV AS. Based on experiences in other sarcomas, we examined (combination) treatment of PARP inhibitor (PARPi) olaparib and temozolomide (TMZ) in UV AS cell lines. METHODS: Previously collected UV AS (n = 47) and non-UV AS (n = 96) patient samples and two UV AS cell lines (MO-LAS and AS-M) were immunohistochemically assessed for PARP1 and SLFN11 expression. Both cell lines were treated with single agents PARPi olaparib and TMZ, and the combination treatment. Next, cell viability and treatment synergy were analyzed. In addition, effects on apoptosis and DNA damage were examined. RESULTS: In 46/47 UV AS samples (98%), PARP1 expression was present. SLFN11 was expressed in 80% (37/46) of cases. Olaparib and TMZ combination treatment was synergistic in both cell lines, with significantly increased apoptosis compared to single agent treatment. Furthermore, a significant increase in DNA damage marker γH2AX was present in both cell lines after combination therapy. CONCLUSION: We showed combination treatment of olaparib with TMZ was synergistic in UV AS cell lines. Expression of PARP1 and SLFN11 was present in the majority of UV AS tumor samples. Together, these results suggest combination treatment of olaparib and TMZ is a potential novel AS subtype-specific treatment option for UV AS patients.

Contains fulltext : 238293.pdf (Publisher’s version ) (Open Access), BACKGROUND: This observational, retrospective effort across Europe, US, Australia, and Asia aimed to assess the activity of systemic therapies in EHE, an ultra-rare sarcoma, marked by WWTR1-CAMTA1 or YAP1-TFE3 fusions. METHODS: Twenty sarcoma reference centres contributed data. Patients with advanced EHE diagnosed from 2000 onwards and treated with systemic therapies, were selected. Local pathologic review and molecular confirmation were required. Radiological response was retrospectively assessed by local investigators according to RECIST. Progression free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method. RESULTS: Overall, 73 patients were included; 21 had more than one treatment. Thirty-three patients received anthracyclines regimens, achieving 1 (3%) partial response (PR), 25 (76%) stable disease (SD), 7 (21%) progressive disease (PD). The median (m-) PFS and m-OS were 5.5 and 14.3 months respectively. Eleven patients received paclitaxel, achieving 1 (9%) PR, 6 (55%) SD, 4 (36%) PD. The m-PFS and m-OS were 2.9 and 18.6 months, respectively. Twelve patients received pazopanib, achieving 3 (25%) SD, 9 (75%) PD. The m-PFS and m-OS were.2.9 and 8.5 months, respectively. Fifteen patients received INF-α 2b, achieving 1 (7%) PR, 11 (73%) SD, 3 (20%) PD. The m-PFS and m-OS were 8.9 months and 64.3, respectively. Among 27 patients treated with other regimens, 1 PR (ifosfamide) and 9 SD (5 gemcitabine +docetaxel, 2 oral cyclophosphamide, 2 others) were reported. CONCLUSION: Systemic therapies available for advanced sarcomas have limited activity in EHE. The identification of new active compounds, especially for rapidly progressive cases, is acutely needed.

Contains fulltext : 245518.pdf (Publisher’s version ) (Open Access), Frequency of scanning has accelerated in the era of personalized medicine and is related, but not restricted, to the exploding number of clinical trials for new cancer treatments. Particularly in drug trials, but also in clinical practice, patients are followed up by scans frequently, which may vary from every 6 to 12 weeks until progression. The authors aimed to raise awareness for this underreported but widely present "Sword of Damocles" scan-related issue also referred to as 'scanxiety.'

Contains fulltext : 244219.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, Epithelioid hemangioendothelioma (EHE) is an extremely rare vascular sarcoma with a very heterogeneous presentation and prognosis. We here present five cases of EHE emphasizing diversity in presentation, treatment, and prognosis. Furthermore, we present a review of the literature on EHE treatment options.

Contains fulltext : 242549.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 240794.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 239290.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 235257.pdf (Publisher’s version ) (Open Access), AIMS: Adolescents and young adults aged 15-39 years with cancer face unique medical, practical and psychosocial issues. In the UK, principal treatment centres and programmes have been designed to care for teenage and young adult patients aged 13-24 years in an age-appropriate manner. However, for young adults (YAs) aged 25-39 years with cancer, little access to age-specific support is available. The aim of this study was to examine this possible gap by qualitatively exploring YA care experiences, involving patients as research partners in the analysis to ensure robust results. MATERIALS AND METHODS: We conducted a phenomenological qualitative study with YAs diagnosed with any cancer type between ages 25 and 39 years old in the last 5 years. Participants took part in interviews or focus groups and data were analysed using inductive thematic analysis. Results were shaped in an iterative process with the initial coders and four YA patients who did not participate in the study to improve the rigor of the results. RESULTS: Sixty-five YAs with a range of tumour types participated. We identified seven themes and 13 subthemes. YAs found navigating the healthcare system difficult and commonly experienced prolonged diagnostic pathways. Participants felt under-informed about clinical details and the long-term implications of side-effects on daily life. YAs found online resources overwhelming but also a source of information and treatment support. Some patients regretted not discussing fertility before cancer treatment or felt uninformed or rushed when making fertility preservation decisions. A lack of age-tailored content or age-specific groups deterred YAs from accessing psychological support and rehabilitation services. CONCLUSIONS: YAs with cancer may miss some benefits provided to teenagers and young adults in age-tailored cancer services. Improving services for YAs in adult settings should focus on provision of age-specific information and access to existing relevant supp

Radboud University, 05 juli 2021, Promotores : Graaf, W.T.A. van der, Jones, R.L. Co-promotores : Husson, O., Desar, I.M.E., Contains fulltext : 233908.pdf (Publisher’s version ) (Open Access)

Radboud University, 14 juni 2021, Promotores : Graaf, W.T.A. van der, Poll-Franse, L.V. van de Co-promotores : Husson, O., Desar, I.M.E., Contains fulltext : 233756.pdf (Publisher’s version ) (Open Access)

Item does not contain fulltext, BACKGROUND: Insight into the causes of colorectal cancer (CRC) in adolescent and young adult (AYA) patients is limited. Without definitive information, patients often shape their own beliefs on the cause of their illness, developing causal attributions. This study aims to examine the causal attributions of CRC in AYA patients, compare these with middle-aged and older adults CRC patient groups and explore the association between causal attributions and psychological distress. METHODS: Two cross-sectional questionnaire studies were conducted among CRC survivors diagnosed between 1998 and 2007 using the population-based PROFILES registry. Three groups were defined by age at diagnosis: AYA (18-39 years; n = 67), middle-aged (40-70 years; n = 1993) and older adult survivors (70+ years; n = 1922). Causal attributions were assessed in a single free-text item from the Brief Illness Perception Questionnaire and psychological distress measured by the Hospital Anxiety and Depression Scale. RESULTS: AYA survivors most often attributed their CRC to heredity (36.4%), lifestyle (14.5%) and chance (10.9%). AYA survivors attributed their CRC to these causes more frequently than middle-aged and older adult CRC survivors. AYA survivors who attributed their CRC to causes out of their control (chance, heredity) showed significantly lower mean scores on anxiety (4.3 vs. 5.6; p < 0.01) compared to AYAs who reported causes within their control (lifestyle, stress). No significant difference was found for depression. CONCLUSION: AYA patients with CRC may benefit from in-depth discussion about the lack of known (biological) causes and how this does not directly imply a lifestyle or stress cause.

Contains fulltext : 235496.pdf (Publisher’s version ) (Open Access)

Contains fulltext : 229742.pdf (publisher's version ) (Open Access)

Contains fulltext : 232106.pdf (Publisher’s version ) (Open Access), AIM: Sunitinib is an oral tyrosine kinase inhibitor approved for the treatment of renal cell carcinoma (RCC) and gastrointestinal stromal tumor (GIST). Because of the large interpatient pharmacokinetic variability and established exposure-response and exposure-toxicity relationships in clinical trial patients, therapeutic drug monitoring (TDM) seems promising for optimizing sunitinib exposure. We aimed to investigate the relationship between sunitinib exposure and treatment outcome in a real-world patient cohort. METHODS: We performed a retrospective observational cohort study in 53 patients with metastatic RCC and 18 patients with metastatic GIST treated with sunitinib and receiving TDM-guided dosing. Time on treatment - as a surrogate for progression-free survival - in patients who achieved adequate sunitinib exposure was compared with patients who did not. Additionaly, the median sunitinib exposure was compared in patients with or without sunitinib-induced toxicity leading to dose reduction. RESULTS: The median time on treatment in patients with RCC who achieved adequate sunitinib exposure (n = 39) was 32 weeks, compared to 15 weeks in patients who did not achieve adequate sunitinib exposure (n = 12) (P = 0.244). In 29 patients (41%) with toxicity leading to dose reduction, sunitinib sum plasma trough concentration (C(trough) ) until dose reduction was significantly higher compared to patients without toxicity leading to dose reduction (median 60 ng/mL vs 44 ng/mL; P < 0.001) and reduced to comparable levels after dose reduction (44 ng/mL; P = 0.488). CONCLUSION: In our real-world patient cohort, patients with sunitinib-induced toxicity requiring dose reduction had significantly higher sunitinib exposure compared to patients without toxicity. The threshold for toxicity, however, was lower compared to that previously described in clinical trials.

Contains fulltext : 233943.pdf (Publisher’s version ) (Open Access)