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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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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, 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. [ABSTRACT FROM AUTHOR]

Introduction: Sarcomas are rare tumours. Early diagnosis is challenging, but important for local control and potentially survival and quality of life(QoL). We investigated (1)the route to diagnosis (RtD) experienced by sarcoma patients, including factors contributing to the length of the RtD from patients' perspective; (2)the impact of the RtD on QoL and care satisfaction; and (3)differences in aims 1–2 between English and Dutch patients. Methods: Fifteen sarcoma patients from The Royal Marsden Hospital, United Kingdom, and Radboud University Medical Centre, The Netherlands, were interviewed, exploring RtD experiences. Interviews were analysed according to qualitative content analysis. Results: The main themes were: patient interval, diagnostic interval, reflection on the RtD and recommendations for improvement. Patient interval was long if symptoms were attributed as benign, did not interfere with daily life or were expected to cease. An incorrect working diagnosis, ineffective process of additional investigations, long referral times and lack of a lead clinician lengthened the diagnostic interval. Long waiting times, false reassurance and inadequate information provision led to dissatisfaction and a high emotional burden. Factors for improvement included increasing awareness of patients and healthcare providers, empowering patients, and having a lead clinician. Conclusion: The RtD of sarcoma patients is complex. Increasing awareness of patients and healthcare providers may contribute to shorten the RtD. [ABSTRACT FROM AUTHOR]

Purpose. Desmoid-type fibromatosis (DTF) is a rare, nonmetastasising soft tissue tumour. Symptoms, unpredictable growth, lack of definitive treatments, and the chronic character of the disease can significantly impact health-related quality of life (HRQoL). We aimed at identifying the most important HRQoL issues according to DTF patients in two countries, in order to devise a specific HRQoL questionnaire for this patient group. Methods. DTF patients and healthcare providers (HCPs) from the Netherlands and the United Kingdom individually ranked 124 issues regarding diagnosis, treatment, follow-up, recurrence, living with DTF, healthcare, and supportive care experiences, according to their relevance. Descriptive statistics were used to calculate priority scores. Results. The most highly ranked issues by patients (n = 29) were issues concerning "tumour growth," "feeling that there is something in the body that does not belong there," and "fear of tumour growth into adjacent tissues or organs" with mean (M) scores of 3.0, 2.9, and 2.8, respectively (Likert scale 1–4). British patients scored higher on most issues compared to Dutch patients (M 2.2 vs. M 1.5). HCPs (n = 31) gave higher scores on most issues compared to patients (M 2.3 vs. M 1.8). Conclusion. This study identified the most relevant issues for DTF patients, which should be included in a DTF-specific HRQoL questionnaire. Additionally, we identified differences in priority scores between British and Dutch participating patients. Field testing in a large, international cohort is needed to confirm these findings and to devise a comprehensive and specific HRQoL questionnaire for DTF patients. [ABSTRACT FROM AUTHOR]

Trabectedin and ifosfamide are among the few cytostatic agents active in advanced soft tissue sarcomas (STSs). Trabectedin is most potent against so-called L-sarcomas (leiomyosarcoma and liposarcoma). The survival gain and cost-effectiveness of these agents in a second-line setting were analysed in the setting of advanced STS after failure of anthracyclines. A prospective observational trial had previously been performed to assess the use of trabectedin in a Dutch real-world setting. Data on ifosfamide monotherapy were acquired from previous studies, and an indirect comparison of survival was made. A state-transition economic model was constructed, in which patients could be in mutually exclusive states of being preprogression, postprogression, or deceased. The costs and quality-adjusted life years (QALYs) for both treatments were assessed from a Dutch health-care perspective. Separate analyses for the group of L-sarcomas and non-L-sarcomas were performed. Trabectedin treatment resulted in a median progression-free survival of 5.2 months for L-sarcoma patients, 2.0 months for non-L-sarcoma patients, and a median overall survival of 11.8 and 6.0 months, respectively. For L-sarcoma patients, trabectedin offered an increase of 0.368 life years and 0.251 QALYs compared to ifosfamide and €20,082 in additional costs, for an incremental cost-effectiveness ratio (ICER) of €80,000 per QALY gained. In the non-L-sarcoma patients, trabectedin resulted in 0.413 less life years and 0.266 less QALYs, at the increased cost of €4,698. The difference in survival between drugs and the acquisition costs of trabectedin were the main influences in these models. Trabectedin was shown to have antitumour efficacy in advanced L-sarcoma. From a health economics perspective, the costs per QALY gained compared to ifosfamide monotherapy that may be acceptable, considering what is currently regarded as acceptable in the Netherlands. [ABSTRACT FROM AUTHOR]

Introduction. Nonsurgical management of patients with desmoid-type fibromatosis (DF) is increasing. This study tries to provide insight on type, usage, and outcome of first-line nonsurgical management strategies. Patients and Methods. From the Dutch Pathology Registry (PALGA), patients with extra-abdominal or trunk/abdominal wall DF, diagnosed between 1993 and 2013, were identified. First-line treatment was analyzed. Best response (BR) using RECIST criteria from start of treatment/surveillance until change of treatment or last follow-up was analyzed. Results. Ninety-one of the 1141 identified patients had first-line nonsurgical management. The percentage of patients treated nonsurgically increased from 0.6% in 1993–1998 to 12.8% in 2009–2013. Thirty-seven patients had surveillance (41%), 35 radiotherapy (38%), and 19 systemic treatment (21%). BR for surveillance was complete response (CR) in 2/37, partial response (PR) in 4/37, stable disease (SD) in 21/37, progressive disease (PD) in 5/37, and unknown in 5/37 patients. BR for radiotherapy was CR in 4/35, PR in 11/35, SD in 16/35, and unknown in 4/35. BR for systemic treatment was CR in 1/19, PR in 1/19, SD in 10/19, PD in 2/19, and unknown in 5/19. Totally, 91% of patients did not progress. Discussion. Given the low percentage (9%) of PD of nonsurgical management, these data can be used in shared decision making with the patient regarding optimal treatment. [ABSTRACT FROM AUTHOR]

Background: We performed a retrospective nationwide study to explore age as a prognostic factor in synovial sarcoma patients.Methods: Data on 613 synovial sarcoma patients were obtained from the Netherlands Cancer Registry. The prognostic relevance of age groups (children, adolescent and young adults (AYAs), adults, and elderly) was estimated by Kaplan-Meier survival curves and multivariable Cox-proportional hazards modelling.Results: A total of 461 patients had localised disease at diagnosis. The 5-year overall survival (OS) was 89.3±4.6%, 73.0±3.8%, 54.7±3.6%, and 43.0±7.0% in children (n=54), AYAs (n=148), adults (n=204), and elderly (n=55), respectively. Treatment modalities had no significant effect on survival in the univariable analysis. Multivariable analysis identified age at diagnosis, tumour localisation, and tumour size as significant factors affecting OS. Both tumour localisation and size were equally distributed over the age groups.Conclusions: We show that outcome of synovial sarcoma patients significantly decreases with age regardless of primary tumour site, size, and treatment. [ABSTRACT FROM AUTHOR]

Background. Gastrointestinal stromal tumors (GIST) are rare and before 2000, patients had a dismal prognosis with a median survival of less than a year after tumor metastasis. However, the median overall survival has increased to more than five years following the introduction of imatinib and other tyrosine kinase inhibitors (TKI). Little is known about the psychosocial consequences of treatment of GIST, but this is important because patients now are treated and live for longer. This cross-sectional study assessed quality of life, distress, and fear of cancer recurrence or progression in patients with GIST. Material and methods. Eighty-six patients with localized or metastatic GIST were asked to participate. Patients completed self-report questionnaires including the EORTC-Quality of Life Questionnaire, Hospital Anxiety and Depression Scale, Impact of Event Scale, Cancer Worry Scale, and Fear of Cancer Recurrence Inventory. Results. Fifty-four patients (median age 63.3 years) completed the questionnaires, 33 (61%) of whom were receiving TKI treatment at the time of the study. Overall, the GIST patients had a good global quality of life, but 28 patients had high levels of fear of cancer recurrence/progression. This high level of fear was not related to patient- or treatment-related variables. These patients experienced significantly higher levels of psychological distress, functional impairments, and difficulty making plans for the future than did patients with lower levels of fear. Conclusions. More attention should be paid to specific cancer-related problems, such as fear of cancer recurrence/progression, in addition to general quality of life issues in patients with GIST. [ABSTRACT FROM AUTHOR]

Objective: Our aim was to investigate the feasibility of completing an exercise program in patients with advanced cancer and to obtain preliminary data of its impact on physical and quality of life (QoL) outcomes. Methods: We conducted a nonrandomized pilot study. Participants were 26 palliative care patients with advanced cancer (mean age=54.5 years; standard deviation [SD] 8.9 years) of the outpatient clinic of the medical oncology and the urology departments of a medical center in The Netherlands. Participants followed an individually graded group exercise program, consisting of resistance training and aerobic exercise, twice a week during 6 weeks. Feasibility of the training program, muscle strength, aerobic fitness, body composition, QoL, fatigue, and physical role, social, and activities of daily living (ADL) functioning were assessed at baseline and immediately after the intervention. Results: Dropout rate during the training period was 35% due to disease progression. After the training period, based on intention to treat analysis, muscle strength and aerobic functional fitness had increased significantly ( p≤0.01). A significant decrease in fat percentage ( p≤0.02) was observed. QoL had increased significantly ( p≤0.02), as well as social ( p≤0.04), physical role ( p≤0.01), and ADL functioning ( p≤0.05). Fatigue decreased significantly on the Checklist Individual Strength (CIS) and RAND-36 questionnaires ( p≤0.02), however not on the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 ( p=0.48). No change in physical functioning was observed with the EORTC QLQ-C30 and RAND-36 (respectively, p=0.33 and p=0.09). Conclusions: These preliminary results show that physical exercise in patients with advanced cancer is feasible. A significant impact was observed on physical and QoL outcomes. These findings need to be confirmed with a larger-scale, randomized controlled trial. [ABSTRACT FROM AUTHOR]

Background. Cancer among adolescents and young adults (AYAs; 15-29 years old) is relatively rare but its incidence is increasing worldwide. To define the extent and nature of the AYA patients, this population-based study was performed to explore trends in cancer incidence, survival and risk of second primary cancers in AYAs. Material and methods. Data from all AYAs diagnosed with cancer between 1989 and 2009 were obtained from the Netherlands Cancer Registry. Age-standardized incidence rates with estimated annual percentage of change (EAPC) and five-year relative survival rates were calculated. Relative survival was used as a good approximation of cause-specific survival. All analyses were stratified by gender, five-year age group and calendar period. In addition, Standardized Incidence Ratios were determined to evaluate the risk of second primary cancers. Results. 23 161 AYAs were diagnosed with cancer between 1989 and 2009. Since 1989 the cancer incidence has increased significantly from 28 to 43 per 100 000 person years in males (EAPC: 1.9) and from 30 to 40 per 100 000 person years in females (EAPC: 1.4). The most frequently diagnosed cancers in male AYAs included testicular cancer, melanoma and Hodgkin's disease, whereas in females melanoma, breast cancer and Hodgkin's disease were the most frequently occurring cancers. Five-year relative survival rates were 80% and 82% for males and females, respectively. Over time, the five-year relative survival increased from 74% to 86% and from 79% to 86% in males and females, respectively. The risk of developing a second primary cancer was increased three to six times in males and two to five times in females, depending on rules for counting second primary cancers. Conclusions. Although the overall survival has improved over time, the progress made in AYAs for specific cancers is still less compared to improvements made in children and adults. This and the increasing incidence and high risk of second primary cancers warrants further research. [ABSTRACT FROM AUTHOR]

Background: There is a continuing debate on the desirability of informing patients with cancer and thereby involving them in treatment decisions. On the one hand, information uptake may be hampered, and additional stress could be inflicted by involving these patients. On the other hand, even patients with advanced cancer desire information on risks and prognosis. To settle the debate, a decision aid will be developed and presented to patients with advanced disease at the point of decision making. The aid is used to assess the amount of information desired. Factors related to information desire are explored, as well as the ability of the medical oncologist to judge the patient's information desire. The effects of the information on patient well-being are assessed by comparing the decision aid group with a usual care group. Methods/Design: This study is a randomized controlled trial of patients with advanced colorectal, breast, or ovarian cancer who have started treatment with first-line palliative chemotherapy. The trial will consist of 100 patients in the decision aid group and 70 patients in the usual care group. To collect complete data of 170 patients, 246 patients will be approached for the study. Patients will complete a baseline questionnaire on sociodemographic data, well-being measures, and psychological measures, believed to predict information desire. The medical oncologist will judge the patient's information desire. After disease progression is diagnosed, the medical oncologist offers the choice between second-line palliative chemotherapy plus best supportive care (BSC) and BSC alone. Randomization will take place to determine whether patients will receive usual care (n = 70) or usual care and the decision aid (n = 100). The aid offers information about the potential risks and benefits of both treatment options, in terms of adverse events, tumour response, and survival. Patients decide for each item whether they desire the information or not. Two follow-up questionnaires will evaluate the effect of the decision aid. Discussion: This study attempts to settle the debate on the desirability of informing patients with cancer. In contrast to several earlier studies, we will actually deliver information on treatment options to patients at the point of decision making. Trial registration: Netherlands Trial Register (NTR): NTR1113. [ABSTRACT FROM AUTHOR]

Purpose: Adjuvant `classical' oral cyclophos-phamide, methotrexate, and 5-fluorouracil (CMF) has long been the mainstay of adjuvant chemotherapy for premenopausal breast cancer patients. The Comprehensive Cancer Center North Netherlands (CCCN) breast cancer working group performed a retrospective audit of treatment guideline adherence and quality of CMF in hospitals in the CCCN area. Methods: The CMF treatment data of 251 consecutive axillary lymph node-positive breast cancer patients <50 years old, diagnosed between 1993 and 1996, were analyzed. Results: Ninety- four patients (42%) completed adjuvant CMF without dose adjustment or delay. Overall median relative dose intensity (RDI) was 92.6 (IQR 85.5-97.7). Sixty patients (24%) had an RDI <85, and 7% had an RDI <65. Myelotoxicity was the main reason for reductions and delays. Of 176 irradiated patients, 96% received radiotherapy simultaneously with CMF. Median CMF dose intensity nor median duration differed between patients who underwent mastectomy, mastectomy and radio- therapy, or breast-conserving therapy. Radiotherapy did not influence the median RDI (94 without versus 92 with radiotherapy). G-CSF, administered at least once to 76 patients, did not result in a higher median RDI. Median RDI was slightly higher when > 3 patients/year (P=0.014) were treated by one specialist or > 10 patients classified for adjuvant chemotherapy yearly in a hospital (P=0.037). Conclusion: The adherence to CMF treatment guidelines was generally good. Simultaneous radiotherapy did not affect the median RDI of CM F. G- CSF had no impact on the median RDI but patient volume did influence the RDI. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with rare cancers face obstacles including delays in diagnosis, inadequate treatments and limited scientific evidence to guide decision making. These obstacles may have a unique impact on their experience with the healthcare system and might be different at various ages. Some aspects of care that shape the experience with the healthcare system include information needs, satisfaction with care and supportive care. Very little is known about these aspects of care, specifically for rare cancer patients. Sarcomas are prime examples of rare cancers and are diagnosed at all ages. In this study, we explored the experience of sarcoma patients (N = 1099) with the healthcare system and looked into detail at whether differences in experience existed between age groups. The results of this nationwide study showed that healthcare experiences differ per age group and we identified needs related to the rarity of these tumors, such as improvements concerning (non-)medical guidance and diagnostic intervals. The aim of this study was to explore the experience of rare cancer patients with the healthcare system and examine differences between age groups (adolescents and young adults (AYA, 18–39 years), older adults (OA, 40–69 years) and elderly (≥70 years)). Dutch sarcoma patients, 2–10 years after diagnosis, completed a questionnaire on their experience with the healthcare system, satisfaction with care, information needs, patient and diagnostic intervals (first symptom to first doctor's visit and first doctor's visit to diagnosis, respectively) and received supportive care. In total, 1099 patients completed the questionnaire (response rate 58%): 186 AYAs, 748 OAs and 165 elderly. Many survivors experienced insufficient medical and non-medical guidance (32% and 38%), although satisfaction with care was rated good to excellent by 94%. Both patient and diagnostic intervals were >1 month for over half of the participants and information needs were largely met (97%). AYAs had the longest patient and diagnostic intervals, experienced the greatest lack of (non-)medical guidance, had more desire for patient support groups and used supportive care most often. This nationwide study among sarcoma survivors showed that healthcare experiences differ per age group and identified needs related to the rarity of these tumors, such as improvements concerning (non-)medical guidance and diagnostic intervals. [ABSTRACT FROM AUTHOR]

Simple Summary: Adolescents and young adults (AYAs, aged 15–39 years) with cancer form a distinct patient population within the oncology care setting that is often overlooked in favour of paediatric and older adult patients. As such, specific knowledge on AYAs and their distinct spectrum of cancers is limited. Worldwide, cancer is increasing and it is among the major causes of death among AYAs. Cancer prognosis among AYAs has also been shown to lag behind that of younger and older patients suffering from similar diseases. To address these problems, better understanding of AYA cancers is needed. This study aims to provide an overview of the specific cancer trends among AYAs and the changes that have occurred in the Netherlands since 1990 in terms of incidence, survival, and mortality. This information will provide a solid foundation from which to guide future studies upon, aimed at acquiring more detailed cancer knowledge within the AYA domain. Adolescent and young adult (AYA) cancer patients, aged 15–39 years at primary cancer diagnosis, form a distinct, understudied, and underserved group in cancer care. This study aimed to assess long-term trends in incidence, survival, and mortality of AYA cancer patients within the Netherlands. Data on all malignant AYA tumours diagnosed between 1990–2016 (n = 95,228) were obtained from the Netherlands Cancer Registry. European age-standardised incidence and mortality rates with average annual percentage change (AAPC) statistics and five-year relative survival rates were calculated. The overall cancer incidence increased from 54.6 to 70.3 per 100,000 person-years (AAPC: +1.37%) between 1990–2016, and increased for both sexes individually and for most cancer types. Five-year relative survival overall improved from 73.7% in 1990–1999 to 86.4% in 2010–2016 and improved for both sexes and most cancer types. Survival remained poor (<60%) for rhabdomyosarcoma, lung, stomach, liver, bladder, and pancreatic carcinomas, among others. Mortality rates among male AYAs overall declined from 10.8 to 6.6 (AAPC: −1.64%) and from 14.4 to 10.1 per 100,000 person-years (AAPC: −1.81%) for female AYAs since 1990. Mortality rates remained unchanged for male AYAs aged 20–24 and 25–29 years. In conclusion, over the past three decades, there has been a considerable increase in cancer incidence among AYAs in the Netherlands. Meanwhile, the survival improved and the mortality overall declined. Survival at five-years now well exceeds above 80%, but did not do so for all cancer types. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumour (GIST) is a disease of older adults and is dominated by KIT/PDGFR mutations. In children, GIST is rare, predominantly occurs in girls, has a stomach location and generally lacks KIT/PDGFR mutations. For young adults (YA), aged 18 to 40 years, the typical phenotypic and genotypic patterns are unknown. We therefore aimed to describe the clinical, pathological and molecular characteristics of GIST in in YA. YA GIST patients registered in the Dutch GIST Registry (DGR) were included, and data were compared to those of older adults (OA). From 1010 patients in the DGR, 52 patients were YA (54% male). Main tumour locations were stomach (46%) and small intestine (46%). GIST genetic profiles were mutations in KIT (69%), PDGFRA (6%), SDH deficient (8%), NF1 associated (4%), ETV6-NTRK3 gene fusion (2%) or wildtype (10%). Statistically significant differences were found between the OA and YA patients (localisation, syndromic and mutational status). YA presented more often than OA in an emergency setting (18% vs. 9%). The overall five-year survival rate was 85%. In conclusion, YA GISTs are not similar to typical adult GISTs and also differ from paediatric GISTs, as described in the literature. In this series, we found a relatively high percentage of small intestine GIST, emergency presentation, 25% non-KIT/PDGFRA mutations and a relatively good survival. [ABSTRACT FROM AUTHOR]

Despite curative intents of treatment in localized malignant peripheral nerve sheath tumours (MPNSTs), prognosis remains poor. This study investigated survival and prognostic factors for overall survival in non-retroperitoneal and retroperitoneal MPNSTs in the Netherlands. Data were obtained from the Netherlands Cancer Registry and the Dutch Pathology Database. All primary MPNSTs were collected. Paediatric cases (age ≤18 years) and synchronous metastases were excluded from analyses. Separate Cox proportional hazard models were made for retroperitoneal and non-retroperitoneal MPNSTs. A total of 629 localized adult MPNSTs (35 retroperitoneal cases, 5.5%) were included for analysis. In surgically resected patients (88.1%), radiotherapy and chemotherapy were administered in 44.2% and 6.7%, respectively. In retroperitoneal cases, significantly less radiotherapy and more chemotherapy were applied. In non-retroperitoneal MPNSTs, older age (60+), presence of NF1, size >5 cm, and deep-seated tumours were independently associated with worse survival. In retroperitoneal MPNSTs, male sex and age of 60+ years were independently associated with worse survival. Survival of R1 and that of R0 resections were similar for any location, whereas R2 resections were associated with worse outcomes. Radiotherapy and chemotherapy administrations were not associated with survival. In localized MPNSTs, risk stratification for survival can be done using several patient- and tumour-specific characteristics. Resectability is the most important predictor for survival in MPNSTs. No difference is present between R1 and R0 resections in both retroperitoneal and non-retroperitoneal MPNSTs. The added value of radiotherapy and chemotherapy is unclear. • Resectability is the most prognostic factor for survival in localized MPNSTs. • In MPNSTs, NF1, older age, tumour size, and depth are associated with poorer survival. • Retroperitoneal MPNST is a small subgroup with a worse prognosis. • R0 and R1 resections have similar survival in MPNSTs of any location. • The added value of radiotherapy and chemotherapy is unclear for survival in MPNSTs. [ABSTRACT FROM AUTHOR]

Background: Adolescents and young adults (AYAs) with Ewing sarcoma have a worse prognosis than children. Population-based survival evaluations stratifying findings by important clinical factors are, however, limited. This Dutch population study comprehensively compared survival of children and AYAs with Ewing sarcoma over three decades considering diagnostic period, tissue of origin, tumor site, and disease stage., Methods: Data on all children (0-17 years, N = 463) and AYAs (18-39 years, N = 379) diagnosed with Ewing sarcoma in the Netherlands between 1990-2018 were collected from the Netherlands Cancer Registry with follow-up until February 2023. Five-year relative survival was calculated using the cohort method. Multivariable analyses were conducted through Poisson regression., Results: Children with Ewing sarcoma had a significantly higher 5-year relative survival than AYAs (65 % vs. 44 %). An increasing trend in survival was noted reaching 70 % in children and 53 % in AYAs in 2010-2018. Results were similar for Ewing bone sarcoma and extraosseous Ewing sarcoma. AYAs had a poorer prognosis than children for most tumor sites and regardless of disease stage. Survival probabilities were 60 % vs. 78 % for localized disease and 20 % vs. 33 % for metastatic disease. Multivariable-regression analysis, adjusted for follow-up time, diagnostic period, sex, disease stage, and tumor site, confirmed increased excess mortality among AYAs compared with children (excess HR: 1.7, 95 % CI: 1.3-2.1)., Conclusions: Despite survival improvements since the 1990s, AYAs with Ewing sarcoma in the Netherlands continue to fare considerably worse than children. This survival disparity was present irrespective of tissue of origin, tumor site, and disease stage., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Limited understanding exists regarding early sarcoma symptoms presented during general practitioner (GP) consultations. The study explores GP visit patterns and recorded diagnoses in the 12 months preceding sarcoma diagnosis., Methods: Sarcoma cases diagnosed from 2010 to 2020 were identified through the Netherlands Cancer Registry alongside general practice data. Sarcoma cases were age and gender matched to cancer-free controls (2:1 or 1:1 ratio)., Results: A total of 787 individuals with soft-tissue sarcoma (STS) and 188 individuals with bone sarcoma (BS) were identified. There was a significant difference in monthly GP contacts from 4 months to the last month before STS diagnosis, and 2 months before BS diagnosis between cases and controls. Most prevalent diagnoses recorded by the GP for STS cases included musculoskeletal neoplasm (26.6%), uncomplicated hypertension (15.6%), and cystitis/other urinary infections (12.2%). For BS cases, musculoskeletal neoplasm (42.8%), knee symptoms/complaints (9.7%), and shoulder symptoms/complaints (9.7%) were most frequent., Conclusions and Discussion: A significant difference in GP contacts between cases and controls preceding sarcoma diagnosis. STS cases were predominantly diagnosed with nonspecific symptoms, whereas BS cases with diagnoses more suggestive of BS. Better understanding of the prediagnostic trajectory could aid GPs in early identification of sarcoma., (© 2024 The Author(s). Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Background: The aim of this population-based registry study was to examine the impact of cancer on employment outcomes in adolescent and young adult (AYA) survivors and their partners and associated sociodemographic and clinical characteristics., Methods: A total of 2456 AYA cancer patients, diagnosed in 2013 and aged 18 through 39 years old, were selected from the Netherlands Cancer Registry and linked to employment data from Statistics Netherlands, from which 1252 partners of AYAs could be identified. For both patients and their partners, a control group with same age, migration background, and sex was selected. The impact (i.e., causal effect) was estimated by implementing a doubly robust difference-in-differences method, from 3 years before to 5 years after cancer diagnosis., Results: Patients suffered a reduced employment probability (3.8 percentage points) and number of hours worked when employed (3.8%). This effect was larger for females, and individuals with a migration background, high tumor stage, or diagnosed with a central nervous system tumor/hematologic malignancy. In regard to employment, no significant effect could be found for the patients' partners, although a 5.5 percentage-point increase in employment probability was found in partners who were either unemployed or worked fewer than 400 hours., Conclusions: A cancer diagnosis significantly affects employment outcomes of AYA patients with cancer. Patients at risk should have access to services such as job counseling to help them return into society in the best possible way. No objective impact on partners' employment outcomes was found; however, subjective well-being was not taken into account., Plain Language Summary: This study estimated the causal effect of a cancer diagnosis on employment outcomes. Adolescent and young adult cancer survivors face a reduction in both employment probability and the number of hours worked when employed. Partners that were unemployed or worked the least number of hours a year before diagnosis had a 5.5 percentage-point increased employment probability, but for other partners effects are small., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Purpose: This study aims to (1) explore the prevalence of patient-reported financial difficulties among GIST patients, differentiating between those currently undergoing tyrosine kinase inhibitor (TKI) treatment and those who are not; (2) investigate associations between financial difficulties and sociodemographic and clinical characteristics, work, cancer-related concerns, anxiety and depression and (3) study the impact of financial difficulties on health-related quality of life., Methods: A cross-sectional study was conducted among Dutch GIST patients diagnosed between 2008 and 2018, who were invited to complete a one-time survey between September 2020 and June 2021. Patients completed nine items of the EORTC item bank regarding financial difficulties, seven work-related questions, the Hospital Anxiety and Depression Scale, Cancer Worry Scale and EORTC QLQ-C30., Results: In total, 328 GIST patients participated (response rate 63.0%), of which 110 (33.8%) were on TKI treatment. Patients currently treated with TKIs reported significantly more financial difficulties compared to patients not on TKIs (17.3% vs 8.7%, p = 0.03). The odds of experiencing financial difficulties was 18.9 (95% CI 1.7-214.7, p = 0.02) times higher in patients who were less able to work due to their GIST diagnosis. Patients who experienced financial difficulties had significantly lower global quality of life and functioning, and more frequently reported psychological symptoms as compared to patients who did not report financial difficulties., Conclusion: Even in a country where the costs of TKIs and follow-up care are covered by health insurance, financial difficulties can be present in GIST patients, especially in patients on TKI treatment, and may negatively influence the quality of life., (© 2024. The Author(s).)

Background: The number of international migrants is increasing worldwide. The four major non-western ethnic groups in the Netherlands are Turkish, Moroccan, Surinamese, and Dutch-Caribbean. This review examined the scientific literature on the views of cancer patients from these four ethnic groups on cancer diagnosis, treatment, and prognosis., Methods: A systematic literature review was conducted using the databases EMBASE, Medline Web of Science, and Cochrane Central Register. Studies with patients who were of Turkish, Moroccan, Surinamese, and Dutch-Caribbean descent were included. Both qualitative and quantitative studies were included, and thematic analysis was performed. The methodological quality was assessed using the Mixed Methods Appraisal Tool., Results: Thirteen studies were conducted in Turkey on Turkish cancer patients, while three were conducted in the Netherlands on Turkish and Moroccan cancer patients. Four themes emerged from the included studies: disclosure of diagnosis, communication, information provision, and decision-making. The majority of cancer patients in Turkey wanted information regarding their diagnosis and treatment. However, disclosure of a cancer diagnosis was rarely discussed with cancer patients in Turkey, whereas in the Netherlands it was provided directly. Family members in both the host and native countries had a strong influence on communication and decision-making. No literature on this topic for Surinamese or Dutch-Caribbean cancer patients was found., Conclusion: Although major ethnic groups live in host countries, there is a lack of knowledge on optimal communication and information disclosure on cancer to patients and their families., Policy Summary: Further research into the views of ethnic groups on how to communicate about cancer is essential to ensuring that every patient receives optimal care and treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.

Background: Patients diagnosed with sarcoma are hypothesized to experience a prolonged route to a cancer diagnosis. This route, the total interval, can be divided into a patient interval (the time from the appearance of symptoms to physician consultation) and diagnostic interval (time from the first consultation to diagnosis). In the current study, the authors investigated these intervals among survivors of sarcoma and identified factors associated with prolonged intervals., Methods: A cross-sectional study was conducted among adult patients with sarcoma 2 to 10 years after diagnosis. Patients completed a questionnaire regarding their total interval, which was linked to clinical data from the Netherlands Cancer Registry. Descriptive statistics were used to describe intervals. Based on Dutch clinical guidelines, a diagnostic interval ≥1 month was considered to be prolonged and an interval ≥3 months was considered as very long. Multivariable regression analyses investigated associations between patient and tumor characteristics and interval length., Results: A total of 1099 participants were included (response rate, 58%); approximately 60% reported a patient interval ≥1 month and 36% reported a patient interval ≥3 months. Risk factors for a very long patient interval were sarcoma of the skin or pelvis, liposarcoma, or rhabdomyosarcoma. Stage III disease was associated with a shorter patient interval. The diagnostic interval length was ≥1 month in 55% of patients and ≥3 months in 28% of patients. Risk factors for a very long diagnostic interval were female sex, age <70 years, or having a synovial sarcoma or chordoma., Conclusions: The patient and diagnostic interval lengths were prolonged in a substantial percentage of this sarcoma survivorship population. Factors found to be associated with the length of the patient interval or the diagnostic interval differed. Creating awareness among (especially young) patients to consult a physician and awareness among physicians to consider a sarcoma diagnosis will contribute to optimization of the total interval., (© 2020 American Cancer Society.)

Introduction: Angiosarcoma is a rare and aggressive malignancy with a high metastatic potential and recurrence rate. Despite optimal treatment with surgery, with or without radiation, the prognosis remains poor and, therefore, new treatment strategies are warranted. Recently, propranolol has effectively been repurposed for the treatment of infantile haemangioma. Propranolol is a β3-sparing antagonist of the β-adrenergic receptor. In infantile haemangioma, the β1, β2 and β3 receptors are highly expressed. Angiosarcoma has several similarities with haemangioma, including its high β-adrenergic receptor expression and the supposedly important role of vascular endothelial growth factor in malignant growth. As a result, propranolol has been administered small scale in individual angiosarcoma cases with promising results. The precise effect of propranolol, however, is not yet established., Methods and Analysis: The goal of this neoadjuvant window of opportunity study is to prospectively evaluate the activity of propranolol monotherapy in patients with cutaneous angiosarcoma. The neoadjuvant setting provides a good opportunity to rapidly evaluate both the clinical response and histological response, without a significant delay in standard anticancer treatment. Fourteen patients with primary, recurrent or metastatic cutaneous angiosarcoma will be included. Propranolol will be administered orally in an escalating dose during 3-6 weeks, before the initiation of standard treatment. The primary endpoint is clinical response according to Response Evaluation Criteria in Solid Tumours, as measured on consecutive coloured photographs or CT/MRI. The histological response will be determined as secondary endpoint, comparing the difference in proliferation index before and after propranolol by measuring the change in immunohistochemistry staining of Ki-67. The study will be considered positive when at least three patients have a response to propranolol., Ethics and Dissemination: Ethical approval was obtained from the Medical Ethical Committee of the Netherlands Cancer Institute. Independent of the outcome, results of this study will be shared and submitted for publication in an international peer-reviewed journal., Trial Registration Number: NL8118; registry through the Netherlands Trial Register., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: Higher imatinib exposure is correlated with longer time to progression, while the variability in exposure is high. This provides a strong rationale for therapeutic drug monitoring, which has therefore been implemented in routine clinical practice in our institute. The aim of this study is to evaluate whether pharmacokinetically (PK)-guided dose increases are feasible in daily clinical practice and result in an improved exposure (C min ≥1100 ng/mL) and longer progression-free survival (PFS)., Methods: This retrospective study included all patients with a gastrointestinal stromal tumour (GIST) in the Netherlands Cancer Institute who started imatinib treatment at a dose of 400 mg and of whom PK plasma samples were available. Of these patients, minimum plasma concentrations (C min ) of imatinib, frequency and successfulness of PK-guided dose increases and PFS in the palliative treatment setting were analysed., Results: In total, 169 consecutive patients were included, of whom 1402 PK samples were collected. In 126 patients (75%), C min was below the efficacy threshold of 1100 ng/mL. In 78 of these patients (62%), a PK-guided dose increase was performed, which was successful in 49 patients (63%). PFS was similar in patients with and without imatinib dose increase. However, due to the small number of patients with progressive disease, no definite conclusions on the effect on PFS could yet be drawn., Conclusion: This is the largest cohort evaluating PK-guided dose increases of imatinib in patients with GIST in routine clinical practice and demonstrating its feasibility. PK-guided dose increases should be applied to optimise exposure in the significant subset of patients with a low C min ., Competing Interests: Conflict of interest statement J.H.B. reports receiving research grants for the institute from Astex, PharmaMar and Roche (outside the submitted work) and is a part time employee, patent holder and stock holder of Modra Pharmaceuticals (a spin-out company developing oral taxane formulations, not related to this study). N.S. reports receiving research grants for the institute from AB Science, Abbvie, Actuate Therapeutics, Amgen, Array, AstraZeneca/MedImmune, Bayer, Blueprint Medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Cantargia, Cytovation, Deciphera, Genentech/Roche, GlaxoSmithKline, Incyte, InteRNA, Lilly, Merck Sharp & Dohme, Merus, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi and Takeda (all outside the submitted work). The other authors declare no competing conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Chemotherapy is the mainstay of treatment for patients with advanced soft tissue sarcomas (STS). Treatment intent is usually palliative, aiming to improve symptoms, stabilise or reduce tumour burden and extend life. Clinical trials have traditionally used radiological response, time to progression and survival as measures of treatment efficacy. Health-related quality of life (HRQoL) is at least equally important or more important than survival for many patients with advanced cancer. Systematically collecting HRQoL data during chemotherapy can provide greater insight into treatment efficacy from the patient perspective.The primary aims of this study are to evaluate HRQoL in patients with advanced STS treated with chemotherapy over time, explore the decision-making process and patient reflection post-treatment., Methods and Analysis: This is an observational, international cohort study for 132 patients aged ≥18 years with advanced STS treated at eight centres (three in the UK, five in the Netherlands). Patients will be recruited prior to starting first-line or third-line chemotherapy and invited to complete questionnaires using the Patient-Reported Outcomes Following Initial treatment and Long-term Evaluation of Survivorship registry (PROFILES); an established international registry for collection of cancer patient-reported outcomes. Online (or paper) questionnaires will be completed at baseline, each cycle of chemotherapy and 2-3 monthly during follow-up. The questionnaire package includes the Decisional Conflict Scale, Control Preferences Scale, Quality-Quantity Questionnaire, treatment expectations, European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30), EORTC financial toxicity items, Work Ability Index, Functional Assessment of Cancer Therapy-General (FACT-G) items and Decisional Regret Scale. Clinical data will be extracted from patient records and linked with questionnaire responses. The primary outcome measure is the change in global HRQoL from baseline to after cycle 4 of first-line chemotherapy (based on published data showing that patients with advanced STS complete a median number of four cycles of first-line chemotherapy)., Ethics and Dissemination: Heath Research Authority and Research Ethics Committee (REC 17/NI/0197). Results from the Health-related quality Of Life In patients with advanced Soft TIssue sarcomas treated with Chemotherapy (HOLISTIC) study will be published in peer-reviewed journals and disseminated at local, national and international conferences. We will also present our findings at any appropriate patient meetings and involve patients in study-related publications., Trial Registration Number: NCT03621332., Competing Interests: Competing interests: RLJ is a consultant for: Adaptimmune, Blueprint, Clinigen, Eisai, Epizyme, Daichii, Deciphera, Immunedesign, Lilly, Merck, Pharmamar. WTAvDG has received research grants from Novartis and has been on advisory board from Bayer. The other authors declare that they have no competing interests., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The behavior of desmoid tumors is unpredictable and varies from spontaneous remission to symptomatic and radiologic progression. This study aimed to evaluate the radiologic and symptomatic course of the disease in patients initially managed with active surveillance., Methods: Patients with a primary desmoid tumor at any anatomic location diagnosed between 1998 and 2016 were identified in a prospectively maintained database from a single sarcoma reference center in the United Kingdom. Inverse univariate Cox proportional hazard regression analyses were conducted to evaluate the course of the disease and indications for initiating treatment., Results: The study identified 168 patients with a primary desmoid tumor initially managed with active surveillance. The tumors were located in the abdominal wall (n = 61, 36%), an extremity (n = 51, 30%), chest wall (n = 30, 18%), intra-abdominal site (n = 15, 9%), or elsewhere (n = 11, 6%). Of all the patients, 36% experienced radiologic progressive disease, 36% had stable disease, and 27% regressed. The patients younger than 50 years were more likely to progress (p = 0.046), whereas the patients with chest wall or upper-extremity tumors reported significantly more pain (p = 0.01). Eventually, 46% of the patients proceeded to treatment. The median time to start of treatment after initial surveillance was 31 months, whereas the median follow-up time for the patients not receiving any treatment was 40.5 months. The indications for initiation of treatment were pain (32%), progression (31%), or both (13%)., Conclusions: Patients with desmoid tumors can be managed with initial active surveillance, although almost half of patients may eventually need treatment. Pain, tumor progression, or both are the most common indications for the initiation of treatment.

In the Netherlands, each year 2700 adolescents and young adults (AYA) aged 18 to 35 years are diagnosed with cancer. AYAs have age-specific problems in the areas of education, work, relationships and children that require specific attention. In 2013, we set up the Dutch national AYA 'Youth and Cancer' [Jong & Kanker] platform in co-creation between AYAs and healthcare professionals to address these problems. In this article we discuss the status and future perspectives of this platform.

Background: This study evaluated ototoxicity in locally advanced head and neck cancer patients treated in the CONDOR study with docetaxel/cisplatin/5-fluorouracil (TPF) followed by conventional radiotherapy with concomitant cisplatin 100 mg/m 2 on days 1, 22, and 43 (cis100+RT) versus accelerated radiotherapy with concomitant cisplatin weekly 40 mg/m 2 (cis40+ART)., Methods: Sixty-two patients were treated in this study. Audiometry was performed at baseline, during TPF, before start of chemoradiotherapy, and 1, 4, 8, and 12 months after treatment., Results: A complete dataset of audiometric data was available of 12 patients treated with high-dose cisplatin and of 11 patients treated with intermediate-dose cisplatin. Patients in the high-dose group showed significant more hearing loss than in the intermediate group at 4 kHz ([z = 1.98; P = .04] and 8 kHz [z = 2.07; P < .03]). Interindividual variation was high in both groups., Conclusion: After induction TPF, more ototoxicity was observed in chemoradiotherapy with cis100+RT than after chemoradiotherapy with cis40+ART., (© 2018 Wiley Periodicals, Inc.)

Background: The purpose of this study was to compare general health-related quality of life (HR-QOL) of thyroid cancer survivors with a normative sample stratified by age at diagnosis (adolescents and young adults 18-35 years; middle-aged adults 36-64 years; elderly 65-84 years), and to compare general HR-QOL and disease-specific symptoms among adolescents and young adults, middle-aged adults, and elderly thyroid cancer survivors in an exploratory population-based cross-sectional study., Methods: All patients diagnosed with thyroid cancer between 1990 and 2008, who were registered in the Eindhoven Cancer Registry, received a survey. Our final sample included 293 thyroid cancer survivors., Results: Compared with a normative sample, adolescents and young adult thyroid cancer survivors showed statistically significant and clinically meaningfully worse physical, role, cognitive, and social functioning, and more fatigue and financial problems. Adolescents and young adult thyroid cancer survivors scored statistically significant and clinically meaningfully better on physical functioning and interest in sex compared with the elderly and had less sympathetic and throat/mouth problems compared with middle-aged adults., Conclusion: Thyroid cancer seems to have a greater impact on younger than older thyroid cancer survivors and the lower HR-QOL in older compared to younger thyroid cancer survivors is probably caused mostly by their age and not the cancer., (© 2018 Wiley Periodicals, Inc.)

Salivary duct carcinoma (SDC) is a subtype of salivary gland cancer with a dismal prognosis and a need for better prognostication and novel treatments. The aim of this national cohort study was to investigate clinical outcome, prognostic factors, androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2) expression. SDC patients diagnosed between 1990 and 2014 were identified by the Nationwide Network and Registry of Histo- and Cytopathology in the Netherlands (PALGA). Subsequently, medical records were evaluated and pathological diagnoses reviewed. Data were analyzed for overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and prognostic factors. AR was evaluated by immunohistochemistry (IHC), HER2 by IHC and fluorescent in-situ hybridization. A total of 177 patients were included. The median age was 65 years, 75% were male. At diagnosis, 68% presented with lymph node metastases and 6% with distant metastases. Median OS, DFS and DMFS were 51, 23 and 26 months, respectively. In patients presenting without distant metastases, the absolute number of positive lymph nodes was associated with poor OS and DMFS in a multivariable analysis. AR and HER2 were positive in 161/168 (96%) and 44/153 (29%) tumors, respectively, and were not prognostic factors. SDC has a dismal prognosis with primary lymph node involvement in the majority of patients. The absolute number of lymph node metastases was found to be the only prognostic factor for DMFS and OS. AR expression and-to a lesser extent-HER2 expression hold promise for systemic treatment in the metastatic and eventually adjuvant setting., (© 2018 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Salivary duct carcinoma, an aggressive subtype of salivary gland cancer, is mostly androgen receptor-positive. Only limited data are available on androgen deprivation therapy (ADT)., Methods: Patients with advanced androgen receptor-positive salivary duct carcinoma treated with first-line ADT were retrospectively evaluated for clinical benefit (ie, partial response [PR] and stable disease, progression-free survival [PFS] and overall survival [OS]). The OS was compared with patients with advanced salivary duct carcinoma who received best supportive care., Results: Thirty-four of 35 patients who were ADT-treated were evaluable: 6 patients had a PR (18%) and 11 had stable disease (32%) leading to a clinical benefit ratio of 50%. The median PFS for the ADT-treated patients was 4 months and the median duration of clinical benefit was 11 months. The median OS was 17 months versus 5 months in 43 patients receiving best supportive care (P = .02)., Conclusion: We recommend ADT in advanced androgen receptor-positive salivary duct carcinoma given its response and clinical benefit. © 2017 Wiley Periodicals, Inc. Head Neck, 2017., (© 2017 The Authors Head & Neck Published by Wiley Periodicals, Inc.)

Background: Although fatigue is the most frequently occurring symptom in patients with cancer, hardly anything is known about fatigue of their informal caregivers and the impact fatigue might have on perceived burden with providing care. We investigated the presence of fatigue in caregivers, its course and the relation of fatigue severity between caregivers and patients. Furthermore, we explored in caregivers whether fatigue severity was correlated to experienced burden., Material and Methods: Informal caregivers and patients on cancer treatment in the palliative phase completed questionnaires at baseline and follow-up (6 months later). To measure fatigue severity, both groups completed the Checklist Individual Strength. Additionally, caregivers completed the Caregivers Strain Index to assess experienced burden with providing care. Descriptive analyses, paired t-tests, χ(2)-tests, Pearson's correlations and regression analysis were performed., Results: At baseline 111 couples (patients and caregivers) participated, at follow-up 75 couples. At both time points 23% of caregivers were severely fatigued. There was no significant correlation between patients and caregivers on fatigue. Higher fatigue in both patients and caregivers was correlated with higher burden in caregivers and over 30% of burden could be explained by fatigue., Conclusion: Almost a quarter of caregivers of patients on active palliative treatment were severely fatigued, which figure remained stable over time. Fatigue in both patients and caregivers was related to caregivers' burden. This observation should be taken into account with the growing demand on caregivers and the increase in cancer treatment options in the palliative setting.

Background: Because of a rise in incidence and more effective treatments, the prevalence of patients with metastatic cancer is increasing fast. When palliative treatment is aimed at maintaining or improving patients' quality of life, knowledge about severe fatigue is clinically relevant because of its debilitating effect, but at present this information is lacking., Objective: This study investigated the prevalence of severe fatigue in patients with various incurable cancers and whether severe fatigue increased with further treatment lines and differed between various cancers and treatment modalities. In addition, a relationship between severe fatigue and other symptoms was examined., Methods: Patients were asked to fill in the Checklist Individual Strength, European Organization of Research and Treatment of Cancer-Quality of Life Questionnaire C30, and the McGill Pain Questionnaire during palliative anticancer treatment, and hemoglobin levels were collected., Results: Of all participating patients (n = 137), 47% were severely fatigued. Patients who received first line of treatment were significantly less often severely fatigued (40%) compared with patients who received further lines (60%). Significantly more severe fatigue was observed when patients had more pain, dyspnea, appetite loss, nausea, vomiting, and constipation., Conclusions: During the phase of palliative anticancer treatment, fatigue was the most common symptom, nearly half of the patients had severe fatigue increasing with further treatment lines. Various treatment-related symptoms were related to more severe fatigue., Implications for Practice: As severe fatigue is significantly related to other symptoms of cancer and its treatment, the screening and treatment of these cancer-related symptoms should be more stringent, as they might negatively influence each other.

Background: Five percent of gastrointestinal stromal tumors (GISTs) are primarily localized in the rectum. We analyzed the outcome of multimodality treatment for rectal GIST in a multicenter retrospective series., Methods: All surgically treated patients with a rectal GIST were identified from four specialized centers in the Netherlands. Primary endpoints were disease-free survival (DFS) and overall survival (OS)., Results: Thirty-two patients (22 men and 10 women) with rectal GISTs were identified. Twenty-two patients received imatinib before surgery for a median of 9 (range 2-53) months (Group 1). Ten patients received no imatinib because of small tumor size or lack of availability (Group 2). Median tumor size before treatment was 9.3 (range 6-17) cm in Group 1 and median 6 (range 4-14) cm in Group 2. A complete resection was possible in 17/22 (77%) patients in Group 1 versus 7/10 (70%) in Group 2. Median DFS was not reached in Group 1, while it was 36 months in Group 2. Median OS was not reached in both groups., Conclusions: Preoperative imatinib leads to downsizing of the tumors in Group 1. However, it has not led to less extensive surgery. The DFS is longer in patients treated with pre- and post-operative imatinib, without an effect on OS., (Copyright © 2012 Wiley Periodicals, Inc.)

Age at diagnosis is a well known prognostic factor in many different malignancies; its significance for patients with osteosarcoma is however controversial. To gain more insight in the prognostic role of age, we performed a retrospective study at our institute. We included 102 patients with de-novo osteosarcoma and formed three age groups to evaluate age specific survival rates: ≤ 14 years, 15-19 years and 20-40 years. Differences in outcome between patients aged 15-19 years treated at either the pediatric department or the adult department of oncology were evaluated. The 5-year overall survival rate (OSR) of the whole population was 53.5%±1.5%. OSR of 70.6%±0.8% was seen in patients ≤ 14 years old, 52.5%±1.1% in patients 15-19 years old and 33.3%±0.9% in the patients aged 20-40 years (p=0.01). Significant differences were observed with regard to stage at presentation (higher in older age groups), size of the tumor (larger in younger age groups) and histological response (more good responders in younger age groups). No significant difference was seen between outcomes of patients aged 15-19 years treated at the pediatric or adult oncology department. In conclusion, younger patients have a significantly better outcome than older patients., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To assess the risk of secondary nonbreast cancers (SNBCs) in a recently treated population-based cohort of breast cancer patients focused on the association with treatment and prognostic implications., Patients and Methods: In 58,068 Dutch patients diagnosed with invasive breast cancer between 1989 and 2003, SNBC risk was quantified using standardized incidence ratios (SIRs), cumulative incidence, and Cox regression analysis, adjusted for competing risks., Results: After a median follow-up of 5.4 years, 2,578 SNBCs had occurred. Compared with the Dutch female population at large, in this cohort, the SIR of SNBCs was increased (SIR, 1.22; 95% CI, 1.17 to 1.27). The absolute excess risk was 13.6 (95% CI, 9.7 to 17.6) per 10,000 person-years. SIRs were elevated for cancers of the esophagus, stomach, colon, rectum, lung, uterus, ovary, kidney, and bladder cancers, and for soft tissue sarcomas (STS), melanoma, non-Hodgkin's lymphoma, and acute myeloid leukemia (AML). The 10-year cumulative incidence of SNBCs was 5.4% (95% CI, 5.1% to 5.7%). Among patients younger than 50 years, radiotherapy was associated with an increased lung cancer risk (hazard ratio [HR] = 2.31; 95% CI, 1.15 to 4.60) and chemotherapy with decreased risk for all SNBCs (HR = 0.78; 95% CI, 0.63 to 0.98) and for colon and lung cancer. Among patients age 50 years and older, radiotherapy was associated with raised STS risk (HR = 3.43; 95% CI, 1.46 to 8.04); chemotherapy with increased risks of melanoma, uterine cancer, and AML; and hormonal therapy with all SNBCs combined (HR = 1.10; 95% CI, 1.01 to 1.21) and uterine cancer (HR = 1.78; 95% CI, 1.40 to 2.27). An SNBC worsened survival (HR = 3.98; 95%CI 3.77 to 4.20)., Conclusion: Breast cancer patients diagnosed in the 1990 s experienced a small but significant excess risk of developing an SNBC.

Goals of Work: This study examined the quality of life (QoL) of cancer patients diagnosed 1-5 years previously and their spouses, with children 4-18 years living at home. Relationships between parents' QoL and the children's functioning were explored., Patients and Methods: 166 cancer patients and their spouses provided information on their QoL (RAND-36) and on their children's functioning (Child Behavior Checklist)., Main Results: Male and female patients scored similarly to a norm population on five domains. Patients' QoL was clinically relevantly and/or statistically lower on social functioning, role limitations because of physical problems, and vitality than the norm. Male spouses' QoL was comparable to the norm. However, female spouses reported better physical functioning but more social problems. QoL varied according to type of cancer, treatment intensity, and recurrence. Using the QoL composite scores, a significant relationship was found between patients' psychosocial and physical functioning and spouses' psychosocial functioning. Patients' psychosocial functioning correlated moderately strongly to weakly with their reports of their younger children's and adolescents' functioning; physical functioning correlated only weakly with adolescents' functioning. The patients' functioning related weakly to moderately strongly to adolescents' self-reports of functioning. Spouses' psychosocial functioning weakly related to their and adolescents' reports of adolescents' functioning., Conclusions: Cancer patients' QoL 1-5 years after diagnosis was decreased in three of eight domains; their spouses seem to be doing well. Parents' physical and psychosocial functioning related weakly to moderately strongly to their children's functioning, depending on the child's age and information source. The patients' functioning related more strongly to the children's functioning than the spouses' did.

Objective: This study examined the relationship between temperament and internalising and externalising problems among children of parents diagnosed with cancer, beyond the effects of socio-demographics, illness-related variables and life events., Materials and Methods: Three hundred and forty adolescent children and their 212 parents diagnosed with cancer participated. Children and parents completed the Youth Self Report and the Child Behaviour Checklist, respectively. Children completed also the Early Adolescent Temperament Questionnaire., Main Results: Daughters of parents with cancer were reported as having more internalising problems than their counterparts did. Prevalence of problems did not depend on children's and parents' age or educational level. Recurrent disease and number of life events experienced by children and parents affected the problems reported. The most important temperament dimensions in the prediction of internalising problems in children were shyness and fear/worry, to a lesser extent, frustration and perceptual sensitivity (children only) and lower scores on pleasure intensity (parents only). Externalising problems were associated with effortful control and in children's reports with frustration. Temperament seemed to be a more important predictor of problems reported by children than parents., Conclusion: Findings suggest that temperament is useful in determining the relative vulnerability of children of parents who have been diagnosed with cancer. Social workers may help parents to recognise individual differences between children and to support children by using techniques that are compatible with the temperament of children.

Background: The number of pathologically examined axillary nodes has been associated with breast cancer survival, and examination of >or=10 nodes has been advocated for reliable axillary staging. The considerable variation observed in axillary staging prompted this population-based study, which evaluated the prognostic effect of a variable number of pathologically examined nodes., Methods: In total, 5314 consecutive breast cancer patients who underwent mastectomy or breast-conserving surgery and axillary dissection between 1994 and 1999 were included. The prognostic effect of the examined number of nodes was assessed with crude and relative survival analysis., Results: A median number of 12 (range, 1-43) nodes were histologically examined, and 59% of the patients had no nodal tumor involvement. The number of examined nodes decreased with age (P<.001) and increased with tumor size (P<.001). Stratified for the number of tumor-positive nodes, overall survival seemed to be worse for patients with <10 compared with patients with >or=10 examined nodes (P<.001), whereas the relative survival did not differ. After adjusting for age, tumor size, number of positive nodes, and detection by screening in a multivariate analysis, the number of examined nodes was not associated with relative survival., Conclusions: This study shows that the association between the number of pathologically examined axillary nodes and overall survival in node-negative and node-positive patients results from stage migration. The absence of an association between the number of examined nodes and relative survival further indicates that the association between the number of examined nodes and crude survival is confounded by age.

Purpose: Determine whether standard or high-dose chemotherapy leads to changes in fatigue, hemoglobin (Hb), mental health, muscle and joint pain, and menopausal status from pre- to post-treatment and to evaluate whether fatigue is associated with these factors in disease-free breast cancer patients., Patients and Methods: Eight hundred eighty-five patients were randomly assigned between two chemotherapy regimens both followed by radiotherapy and tamoxifen. Fatigue was assessed using vitality scale (score < or = 46 defined as fatigue), poor mental health using mental health scale (score < or = 56 defined as poor mental health) both of Short-Form 36, muscle and joint pain with Rotterdam Symptom Checklist, and Hb levels were assessed before and 1, 2, and 3 years after chemotherapy., Results: Fatigue was reported in 20% of 430 assessable patients (202 standard-dose, 228 high-dose) with at least a 3-year follow-up, without change over time or difference between treatment arms. Mean Hb levels were lower following high-dose chemotherapy. Only 5% of patients experienced fatigue and anemia. Mental health score was the strongest fatigue predictor at all assessment moments. Menopausal status had no effect on fatigue. Linear mixed effect models showed that the higher the Hb level (P = .0006) and mental health score (P < .0001), the less fatigue was experienced. Joint (P < .0001) and muscle pain (P = .0283) were associated with more fatigue., Conclusion: In 3 years after treatment, no significant differences in fatigue were found between standard and high-dose chemotherapy. Fatigue did not change over time. The strongest fatigue predictor was poor mental health.

This study investigates emotional and behavioural problems in children of parents diagnosed with cancer and examines the relationship with demographic and illness-related variables. Furthermore, agreement and differences between informants regarding child's functioning were examined. Members of 186 families in which a parent had been diagnosed with cancer participated. More emotional problems were reported for latency-aged sons (ill parents) and adolescent daughters (ill parents; self-reports), whereas also better functioning was reported in adolescent children (spouses), compared to the norm group. Age and gender-effects were found: latency-aged sons were perceived as having more emotional problems than adolescent sons (ill parents); adolescent daughters as having more emotional and behavioural problems than adolescent sons (ill parents; self-reports). Results indicated a higher prevalence of problems when the father was ill than when the mother was (spouses and self-reports). The treatment intensity affected adolescent daughter's functioning (spouses), whereas adolescent son's functioning was affected by relapsed disease (self-reports). Adolescents and mothers perceived comparable levels of problems, but fathers perceived problems in children to be less prevalent. Findings suggest that adolescent daughters and latency-aged sons are at risk for emotional problems following the diagnosis of cancer in a parent. The perception of child's functioning and potential influencing variables varied according to informant.

Purpose: Recently, we found a certain haplotype in the human leukocyte antigen Class III subregion to be associated with breast cancer. Epidemiologic studies have shown that breast cancer and colorectal cancer have several risk factors in common. In view of these studies and because polymorphisms located in the human leukocyte antigen III region have been found to be associated with colorectal cancer, we wondered whether the same region also is involved in colorectal cancer susceptibility., Methods: The human leukocyte antigen region was genotyped with 14 microsatellite markers in germline DNA from 643 colorectal cancer patients and 841 family-based controls. Association analyses and the Haplotype Sharing Statistic were used to search for differences between patients and controls. Subgroup analyses were performed for gender, age at diagnosis, and localization of the tumor., Results: The Haplotype Sharing Statistic analysis revealed neither a difference in mean haplotype sharing between all patients and controls, nor in any of the subgroups. The single allele, genotype, and two-locus association analyses for all patients and for the different subgroups did not show an association with colorectal cancer for the 14 microsatellite markers. Also, no association was observed between the tumor necrosis factor-beta polymorphism and colorectal cancer., Conclusions: No association was observed between commonly occurring haplotypes and alleles in the human leukocyte antigen region and colorectal cancer risk.

BRCA1 and BRCA2 germline mutations account for <5% of breast cancer cases. Less penetrant breast cancer susceptibility genes are likely to exist. Earlier studies have suggested involvement of the HLA region. The HLA region was genotyped with 24 microsatellite markers and markers for two single nucleotide polymorphisms (SNPs) in TNFalpha and TNFbeta, in germline DNA from 956 breast cancer patients and 1271 family-based controls. Association analyses and the haplotype sharing statistic (HSS) were used to search for differences in haplotype sharing between patients and controls. Based on criteria known to influence genetic breast cancer risk, patients were divided into groups of high, moderate and low risk. The HSS revealed a significant difference in mean haplotype sharing between patients and controls for four consecutive markers (D6S2671, TNFa, D6S2672 and MICA), the highest being at D6S2671 (P=0.017). Subgroup analyses showed that moderate-risk patients were responsible for this difference, with the strongest association for D6S2672 (P=0.0009). A single haplotype was more frequent and longer in moderate-risk patients than in controls. The results were confirmed with association analyses. Individuals homozygous for haplotype 110-184 (D6S2672-MICA) were observed in 9.0% of moderate-risk patients and 1.5% of controls [odds ratio (OR)=7.14], while heterozygotes were at a lower risk (OR=1.41), suggesting a recessive effect. No association was observed between the two SNPs in TNFalpha (-308) and TNFbeta (intron 1) and breast cancer risk. The results reveal a potential role of the HLA class III subregion in susceptibility to breast cancer in patients at moderate familial risk.