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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. This population‐based registry study provides insight in the impact of cancer on employment outcomes in adolescent and young adult (AYA) cancer survivors and their partners until 5 years after diagnosis. AYA cancer survivors and partners at risk should have access to services to help them return into society in the best way possible. [ABSTRACT FROM AUTHOR]

Background: Personalized dosing based on measurement of individual drug levels and adjusting the dose accordingly can improve efficacy and decrease unnecessary toxicity of oncological treatment. For imatinib, sunitinib, and pazopanib, this therapeutic drug monitoring (TDM)‐guided dosing is, however, not routinely used, despite accumulating evidence favoring individualized dosing. Therefore, we aimed to identify and quantify (potential) barriers and facilitators in TDM‐guided dosing for imatinib, sunitinib, and pazopanib. Methods: We performed a mixed methods study among all stakeholders involved: patients, healthcare professionals (HCPs), pharmaceutical companies, and health insurance companies. During the first qualitative part of this study, we performed semi‐structured individual interviews and one focus group interview to identify all (potential) barriers and facilitators, and during the second quantitative part of this study, we used a web‐based survey to quantify these findings. The interviews addressed the six domains of the implementation of change model of Grol and Wensing: (1) the innovation itself; (2) the HCP; (3) the patient; (4) social context; (5) organizational context; and (6) finances, law, and governance. Results: In the qualitative study, we interviewed 20 patients, 18 HCPs and 10 representatives of pharmaceutical and health insurance companies and identified 72 barriers and 90 facilitators. In the quantitative study, the survey was responded by 66 HCPs and 58 patients. Important barriers were on the domain of the HCP, such as a lack of experience with TDM (36.4%), on the domain of the patient, such as lack of awareness of TDM (39.7%), and the processing time for measurement and interpretation of the TDM result (40.9%) (organizational domain). Important facilitators were education of HCPs (95.5%), education of patients (87.9%) and facilitating an overview of when and where TDM measurements are being performed (86.4%). Conclusion: We identified and quantified important barriers and facilitators for the implementation of TDM‐guided dosing for imatinib, sunitinib, and pazopanib. Based on our results, the implementation strategy should mainly focus on educating both HCPs and patients and on the organizational aspect of TDM. [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]

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 increasingly recognized as a distinct oncological age group with its own psychosocial challenges and biological characteristics.Social functioning has been shown to be severely affected in AYA cancer survivors.A population‐based questionnaire study to identify AYA sarcoma survivors with impaired social functioning (ISF) and determine factors associated with ISF was conducted. 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‐orientated but also focuses on the psychological and social domains. More than one‐quarter of adolescent sarcoma survivors experience impaired social functioning 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BACKGROUND: No prospective trial with anthracycline‐based chemotherapy has individually assessed response in a well‐differentiated (WD)/dedifferentiated (DD) liposarcoma patient cohort. We conducted a retrospective analysis of first‐line chemotherapy in liposarcoma of intra‐abdominal origin (IA‐LPS) in patients who had entered the European Organisation for Research and Treatment of Cancer (EORTC)/Soft Tissue and Bone Sarcoma Group (STBSG) trials. METHODS: We searched for all adult patients treated with first‐line chemotherapy for advanced IA‐LPS in the EORTC STBSG phase 2 and 3 trials from 1978. Treatment was aggregated into 5 groups: anthracycline alone, ifosfamide alone, doxorubicin plus ifosfamide (D+IFO), doxorubicin/cyclophosphamide/vincristine/dacarbazine, and "other" (brostallicin, trabectedin). Response was assessed prospectively by Response Evaluation Criteria in Solid Tumors or World Health Organization criteria. Progression‐free survival (PFS) and overall survival (OS) were computed by Kaplan‐Meier method. RESULTS: A total of 109 patients with IA‐LPS from 13 trials were identified (104 evaluable for response). Overall, there were 10/109 (9.2%) responders: 3/48 (6.3%) in the anthracycline alone group, 2/15 (13%) in the ifosfamide alone group, and 4/18 (22%) in the D+IFO group. At the 10‐month median follow‐up (interquartile range, 6‐24), the median OS was 19 months (95% CI, 15‐21) and median PFS 4 months (95% CI, 3‐6). D+IFO achieved a not statistically significant longer median PFS (12 months) and median OS (31 months) than observed with other regimens. Univariate/multivariate analysis did not identify prognostic factors. CONCLUSIONS: Cytotoxic chemotherapy, in particular anthracycline alone, had marginal activity in advanced IA‐LPS. Ifosfamide‐containing regimens showed higher activity, although it was not statistically significant and in a small number of cases, with the combination of doxorubicin and ifosfamide appearing to be the more active regimen available in fit patients. This series provides a benchmark for future trials on new drugs in WD/DD liposarcoma.; [ABSTRACT FROM AUTHOR]

Surviving childhood cancer and surviving cancer in adolescence or young adulthood may present with psychosocial similarities and differences. A clearer delineation for these 2 groups is warranted. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: We performed a randomized controlled trial (RCT) to investigate whether regular screening with the distress thermometer (DT) by a nurse improved global quality of life (QOL) of patients with breast cancer (BC) treated with curative intent.Methods: BC patients were randomized between regular screening for distress with a nurse-led DT intervention (NDTI) and usual care (UC). Both groups filled out questionnaires at baseline, after each received treatment modality and at follow-up visits up to 2 years. At these points, the intervention group received also the NDTI. The primary outcome was the global QOL of the EORTC QLQ C30 at 2 years after the end of treatment. Analyses were done on an intention-to-treat basis, using analysis of covariance (ANCOVA), generalized least squares, and interaction analyses.Results: Of 194 randomized patients, 153 filled out the questionnaires up to 2 years after treatment. There was no significant difference between NDTI and UC in global QOL 2 years after the end of treatment (mean diff. = -1∙273, P = .610; 95% CI [-6.195; 3.649]). Subgroup analysis of patients who received multimodality treatment (surgery, radiotherapy, and chemotherapy, n = 66) showed a significant between-group difference in global QOL over time (mean diff. = -10, P < .001; 95% CI [-14.835; -5.167]) together with other secondary outcome measures in favor of the NDTI.Conclusion: NDTI did not lead to a significant improvement in global QOL 2 years after the end of treatment for patients with BC. However, the findings indicate that BC patients who received multimodality treatment may benefit from NDTI. [ABSTRACT FROM AUTHOR]

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/m2 on days 1, 22, and 43 (cis100+RT) versus accelerated radiotherapy with concomitant cisplatin weekly 40 mg/m2 (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. [ABSTRACT FROM AUTHOR]

Before the ICI era, patients with advanced solid cancer had a very high chance of recurrence or progressive disease and did not live long enough to develop imaging - induced secondary cancer. 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. Despite the large numbers of scans which patients undergo, waiting for results gets harder with every scan because it is potentially even more life-changing/shortening than the last [Patient]. Given scan regimes of every 6 to 12 weeks, scanning puts a high burden on patients' emotional functioning. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The prognosis of adult soft tissue sarcoma (STS) patients with metastases is generally poor. As little is known about the impact of the involvement of different metastatic sites and the extent of pulmonary lesions on the outcome for patients receiving first‐line chemotherapy, we aimed to establish prognostic factors for STS patients with lung metastases only. A retrospective, exploratory analysis was performed on 2,913 metastatic STS patients who received first‐line chemotherapy. Detailed information from 580 patients who had lung metastases only, was used for prognostic factor analysis. Patients with lung metastases only were more often asymptomatic and had undergone complete primary tumor resection more frequently compared to patients with additional metastases outside the lung or without lung metastases. For extremity STS, the incidence of lung metastases only was much higher compared to non‐extremity STS. Lung involvement only was an independent favorable prognostic factor for overall survival (OS) with regard to metastatic site. Within this subgroup, in a multivariate model, other factors associated with improved OS included: good performance status (PS), no progression at primary site, low histological grade, younger age, long interval between initial diagnosis and trial registration, and smaller diameter of the largest lung lesion. This unique analysis on prognostic factors in STS patients with lung metastases confirms well‐known patient factors (such as age and PS), and tumor characteristics (including tumor grade, interval between primary diagnosis, and metastases), but also identifies diameter of the largest lung lesion as a new prognostic factor. Knowledge about these factors may support decision‐making within multidisciplinary tumor boards. [ABSTRACT FROM AUTHOR]

Abstract: 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 [ABSTRACT FROM AUTHOR]

Background There is an ongoing debate about the value of (neo-)adjuvant chemotherapy in high- and intermediate-grade osteosarcoma of the head and neck. Methods All records of patients older than 16 years diagnosed with osteosarcoma of the head and neck in the Netherlands between 1993 and 2013 were reviewed. Results We identified a total of 77 patients with an osteosarcoma of the head and neck; the 5-year overall survival (OS) was 55%. In 50 patients with surgically resected high- or intermediate-grade osteosarcoma of the head and neck younger than 75 years, univariate and multivariable analysis, adjusting for age and resection margins, showed that patients who had not received chemotherapy had a significantly higher risk of local recurrence (hazard ratio [HR] = 3.78 and 3.66, respectively). Conclusion In patients younger than 75 years of age with surgically resected high- and intermediate-grade osteosarcoma of the head and neck, treatment with (neo-)adjuvant chemotherapy resulted in a significantly smaller risk of local recurrence. Therefore, we suggest (neo-)adjuvant chemotherapy in patients amenable to chemotherapy. © 2016 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck 39: 140-146, 2017 [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to compare the occurrence of cisplatin-induced nephrotoxicity between concomitant chemoradiotherapy with high versus intermediate-dose cisplatin. Methods One hundred forty-four patients with locally advanced head and neck or nasopharyngeal cancer (NPC) were included; 40 patients received cisplatin 100 mg/m2 (high dose) on days 1, 22, and 43, and 104 patients received cisplatin 40 mg/m2 weekly (intermediate dose) during 6 weeks in combination with radiotherapy. Results During treatment with intermediate-dose cisplatin, 6.7% developed an increase of ≥50% serum creatinine versus 60.0% treated with high-dose cisplatin ( p < .05). Nephrotoxicity (all grades) scored by Common Toxicity Criteria for Adverse Events (CTCAE) version 3.0 or CTCAE version 4.03 was 53% and 100% in the high-dose group and 4.8% and 68% in the intermediate-dose group, respectively. Conclusion Significantly less nephrotoxicity occurs during chemoradiotherapy with intermediate-dose cisplatin compared with high-dose cisplatin. The CTCAE version 4.03 seems to be more appropriate in scoring nephrotoxicity than the CTCAE version 3.0. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1575-E1581, 2016 [ABSTRACT FROM AUTHOR]

Background The purpose of this report was to present the results of accelerated radiotherapy (RT) with concomitant weekly cisplatin in head and neck cancer. Methods One hundred six patients received concomitant cisplatin 40 mg/m2 weekly with accelerated RT up to a dose of 68 Gy over 5.5 weeks. Results Ninety-nine percent of the patients received planned RT and 90% received ≥5 cycles of cisplatin. Moist desquamation of skin developed in 45% and confluent mucositis in 82%. Feeding tubes were required in 79% of the patients, and after 12 months in 4%. One patient developed nephrotoxicity. Three-year locoregional control, disease-free survival (DFS), and overall survival (OS) were 72%, 54%, and 61%, respectively. Human papillomavirus (HPV) status was positive on polymerase chain reaction (PCR) and p16 in 11 of 50 patients with oropharyngeal carcinoma. Three-year OS was 81% and 66% in HPV-positive versus HPV-negative patients with oropharyngeal carcinoma. Conclusion Concomitant weekly cisplatin 40 mg/m2 with accelerated RT was well tolerated and treatment compliance was high. © 2015 Wiley Periodicals, Inc. Head Neck 38: E559-E565, 2016 [ABSTRACT FROM AUTHOR]

BACKGROUND Health-related quality of life (HRQoL) was an exploratory endpoint in the PALETTE trial, a global, double-blind, randomized, phase 3 trial of pazopanib 800 mg versus placebo as second-line or later treatment for patients with advanced soft tissue sarcoma (N = 369). In that trial, progression-free survival was significantly improved in the pazopanib arm (median, 4.6 vs 1.6 months; hazard ratio, 0.31; P < .001), and toxicity of pazopanib consisted mainly of fatigue, diarrhea, nausea, weight loss, and hypertension. METHODS HRQoL was assessed using the 30-item core European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire (EORTC QLQ-C30) at baseline and at weeks 4, 8, and 12 in patients who received treatment on protocol. The primary HRQoL endpoint was the EORTC QLQ-C30 global health status scale. RESULTS Compliance with HRQoL assessments was good, ranging from 94% at baseline to 81% at week 12. Differences in scores on the EORTC QLQ-C30 global health status subscale between the 2 treatment arms were not statistically significant and did not exceed the predetermined, minimal clinically important difference of 10 points ( P = .291; maximum difference, 3.8 points). Among the other subscales, the pazopanib arm reported significantly worse symptom scores for diarrhea ( P < .001) loss of appetite ( P < .001), nausea/vomiting ( P < .001), and fatigue ( P = .012). In general, HRQoL scores tended to decline over time in both arms. CONCLUSIONS HRQoL did not improve with the receipt of pazopanib. However, the observed improvement in progression-free survival without impairment of HRQoL was considered a meaningful result. The toxicity profile of pazopanib was reflected in the patients' self-reported symptoms but did not translate into significantly worse overall global health status during treatment. Cancer 2015;121:2933-2941. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background Aggressive fibromatosis (AF) or desmoid tumor of the head and neck region is a rare, usually unresectable, benign soft tissue tumor with locally aggressive behavior. Methods and Results A 31-year-old woman presented with a progressive trismus, a swelling in the retromandibular area, as well as loss of sensibility of the maxillary and mandibular branch of the trigeminal nerve. MRI of the head and neck revealed an infiltrative mass involving the masticator, parapharyngeal, and prevertebral and paravertebral space on the left with intracranial extension through the orbital fissure. After the fifth biopsy, 15 months after presentation, the diagnosis of AF was made. The tumor was unresectable, so intensity-modulated radiotherapy was given with curative intent using a total dose of 60 Gy in 30 fractions of 2 Gy. After 16 months, she showed progressive disease, for which tamoxifen 40 mg twice daily was started with a good response for 2 years. After that, she started with sorafinib, on which she has stable disease now. Conclusion The often long delay in proper diagnosis and the treatment challenges of a desmoid tumor are illustrated in this case. Furthermore, this article reviews the literature concerning AF, especially of the head and neck region. Head Neck, 2013 [ABSTRACT FROM AUTHOR]

BACKGROUND: Pigmented villonodular synovitis (PVNS) (also known as diffuse-type giant cell tumor) and tenosynovial giant cell tumors (TGCT) are rare, usually benign neoplasms that affect the synovium and tendon sheaths in young adults. These tumors are driven by the overexpression of colony stimulating factor-1 (CSF1). CSF1 is expressed by a minority of tumor cells, which, in turn attract non-neoplastic inflammatory cells that express CSF1 receptor (CSF1R) through a paracrine effect. METHODS: Imatinib mesylate (IM) blocks CSF1R, and previous case reports indicated that it also exerts antitumor activity in PVNS. The authors conducted a multi-institutional retrospective study to assess the activity of IM in patients with locally advanced/metastatic PVNS/TGCT. RESULTS: Twenty-nine patients from 12 institutions in Europe, Australia, and the United States were included. There were 13 men, the median age was 41 years, and the most common site of disease was the knee (n = 17; 59%). Two patients had metastatic disease to the lung and/or bone. Five of 27 evaluable patients had Response Evaluation in Solid Tumor (RECIST) responses (overall response rate, 19%; 1 complete response and 4 partial responses), and 20 of 27 patients (74%) had stable disease. Symptomatic improvement was noted in 16 of 22 patients (73%) who were assessable for symptoms. Despite a high rate of symptomatic improvement and a favorable safety profile, 6 patients discontinued because of toxicity, and 4 patients decided to discontinue IM for no clear medical reason. CONCLUSIONS: IM displayed interesting activity in patients with PVNS/TGCT, providing proof of concept for targeting CSF1R in this disease. The authors concluded that the benefits of alleviating morbidity in patients with localized PVNS/TGCT must be balanced against the potential toxicity of chronic drug therapy. Cancer 2011;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objective: This study aims to identify the predictive power of adolescents', parents', and illness characteristics on the functioning of adolescents when a mother has cancer. Methods: Two hundred and seventy-one adolescents, 128 mothers with cancer, and 96 spouses completed standardized questionnaires 1-5 years after diagnosis. Stress response symptoms (SRS), internalizing and externalizing problems were assessed in adolescents. Parents' SRS, trait anxiety, marital satisfaction, and parent-adolescent communication were assessed in parents. Descriptive statistics and multilevel analyses accounting for non-independence of observations within groups were used. Results: Descriptive analyses showed clinically elevated SRS in 20% of the sons and 30% of the daughters. Daughters experienced more internalizing problems than norm group girls. Multilevel analyses showed that adolescents' female gender and older age were associated with impaired child functioning. Higher levels of parents' trait anxiety and SRS, marital dissatisfaction, and poorer parent-adolescent communication were significant predictors also. Recurrent disease was associated with SRS and internalizing problems, and more intensive treatment with externalizing problems. Female gender and poorer parent-adolescent communication were overall the best predictors. Conclusions: Having a mother with cancer may have far-reaching consequences for more than a quarter of the adolescent offspring. The multilevel approach of this study identified individual-level adolescent' risk characteristics as well as family-level risk characteristics for mental health problems. Adolescents at risk should be referred to health-care professionals specialized in working with families to help them to adapt to their parent's illness. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article reports on current treatment options for bone metastases in malignancy. Because of the rise in the rate of cancer incidence worldwide, a rise in bone metastases, especially in the spine, are observed as well. A historical overview of the developments in the treatment of bone metastases revealed that external beam radiotherapy is the foundation of spinal extradural metastasis. Other treatments can be considered, such as surgical treatment, vertebroplasty or kyphoplasty.

Objectives To evaluate former Buruli ulcer disease (BUD) patients to assess the factors associated with functional limitations and subsequent employment or schooling. Methods The previously validated Buruli ulcer functional limitation score (BUFLS) questionnaire and interviews about educational and professional consequences incurred by BUD. Results Of 638 participants, 362 (57%) had a functional limitation after a median period of almost 4 years after treatment for BUD. A lesion on a joint, older age, female gender, a lesion on a distal part of an extremity and a persistent wound were found to be independent risk factors for stopping work or education. The same risk factors applied to the development of a functional limitation. Both functional limitations and financial difficulties due to BUD disease often led to job loss and school dropout. Conclusions Rehabilitation programmes are urgently needed to diminish the suffering from the functional limitations and employment or schooling problems caused by BUD. [ABSTRACT FROM AUTHOR]

Imaging of P-glycoprotein (P-gp) function in the blood–brain barrier (BBB) may support development of strategies, which will improve drug delivery to the brain. [11C]verapamil has been developed as a positron emission tomography (PET) tracer, to image P-gp function in vivo. Ideally, for the purpose of brain imaging, tracers should have a log P between 0.9 and 2.5. The β-receptor antagonist carvedilol is a P-gp substrate with a log P=2.0, and can be labeled with [11C]. The aim of this study was to determine whether the P-gp substrate [11C]carvedilol can be used as a PET tracer for visualisation and quantification of the P-gp function in the BBB.Cellular [11C]carvedilol accumulation in GLC4, GLC4/P-gp, and GLC4/Adr cells increased three-fold in the GLC4/P-gp cells after pretreatment with cyclosporin A (CsA) whereas no effect of MK571 could be determined in the GLC4/Adr cells.Ex vivo [11C]carvedilol biodistribution studies showed that [11C]carvedilol uptake in the brain was increased by CsA. [11C]carvedilol uptake in other organs was not affected by CsA.Autoradiography studies of rat brains showed that [11C]carvedilol was homogeneously distributed over the brain and that pretreatment with CsA increased [11C]carvedilol uptake.In vivo PET experiments were performed with and without P-gp modulation by CsA. P-gp mediated transport was quantified by Logan analysis of the PET data, calculating the distribution volume (DV) of [11C]carvedilol in the brain. Logan analysis resulted in excellent fits, revealing that [11C]carvedilol is not trapped in the brain. Brain DV of [11C]carvedilol showed a dose-dependent increase of maximal three-fold after CsA pretreatment. Above 15 mg kg−1, no change in DV was found. Compared to [11C]verapamil less CsA was needed to reach maximal DV, suggesting that [11C]carvedilol kinetics is a more sensitive tool to in vivo measure P-gp function.British Journal of Pharmacology (2005) 145, 1045–1051. doi:10.1038/sj.bjp.0706283; published online 13 June 2005 [ABSTRACT FROM AUTHOR]

The purpose of this study of treated Buruli ulcer patients in Ghana was to identify and assess late sequelae of treated Buruli ulcer using a goniometer, and to develop a scoring system for functional limitations. Of 78 patients, 58% (n = 45) had a reduction in the range of motion of one or more joints: 30% (n = 23) had one or more functional limitations of the leg and 21% (n = 16) of the arm; 49% (n = 38) had a functional limitation. Of all patients with affected knees, the predicted average extent of limitation was 63%. In patients with affected ankles, limitation was 78% on average; in those with elbow involvement, this was 76% on average, and in wrists involved, 65%. All of the hands involved were markedly restricted. We propose a simplified and functional scoring system that should be tested for validation in a second patient sample, and, if properly validated and adjusted, can be used in future intervention trials. [ABSTRACT FROM AUTHOR]

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., (© 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Tyrosine kinase inhibitors (TKIs) are anti-cancer drugs that target tyrosine kinases, enzymes that are involved in multiple cellular processes. Currently, multiple oral TKIs have been introduced in the treatment of solid tumours, all administered in a fixed dose, although large interpatient pharmacokinetic (PK) variability is described. For imatinib, sunitinib and pazopanib exposure-treatment outcome (efficacy and toxicity) relationships have been established and therapeutic windows have been defined, therefore dose optimization based on the measured blood concentration, called therapeutic drug monitoring (TDM), can be valuable in increasing efficacy and reducing the toxicity of these drugs. In this review, an overview of the current knowledge on TDM guided individualized dosing of imatinib, sunitinib and pazopanib for the treatment of solid tumours is presented. We summarize preclinical and clinical data that have defined thresholds for efficacy and toxicity. Furthermore, PK models and factors that influence the PK of these drugs which partly explain the interpatient PK variability are summarized. Finally, pharmacological interventions that have been performed to optimize plasma concentrations are described. Based on current literature, we advise which methods should be used to optimize exposure to imatinib, sunitinib and pazopanib., (© 2019 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Aims: We investigated whether major gastrectomy influences the plasma exposure of regorafenib and treatment outcome., Methods: Efficacy and pharmacokinetic data from 133 gastrointestinal stromal tumour patients included in a phase III trial were analysed. Patients were subdivided into 2 groups according to the extent of the gastrectomy (no/nonsignificant gastrectomy and major gastrectomy). Progression-free survival (PFS) on regorafenib was measured and regorafenib and its pharmacological active metabolites plasma exposure were measured., Results: A total of 133 patient were included, of whom 27 underwent major gastrectomy. In patients with no/nonsignificant gastrectomy the median PFS was 145 (interquartile range 43-281) days. The PFS in patients with a major gastrectomy was 172 (interquartile range 57-280) days. Regorafenib pharmacokinetic samples were collected in 80 patients of which 19 patients with a major gastrectomy and 61 patients with no/nonsignificant gastric surgery. The average ± standard deviation total concentration of regorafenib including the metabolites M-2 and M-5 was 6.9 ± 1.53 μmol/L and 6.7 ± 1.56 μmol/L in patient with major gastrectomy and no/nonsignificant gastrectomy respectively., Conclusion: Our study shows that major gastrectomy did not influence plasma exposure of regorafenib and metabolites. In addition, no difference in PFS between the subgroups was seen., (© 2019 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Aim: Fixed dose oral tyrosine kinase inhibitors imatinib, sunitinib and pazopanib show a high interpatient variability in plasma exposure. A relationship between plasma exposure and treatment outcome has been established, which supports the rationale for dose optimization of these drugs. The aim of this study was to monitor how many patients reached adequate trough levels after therapeutic drug monitoring-based dose optimization in daily practice., Methods: A cohort study was performed in patients treated with imatinib, sunitinib or pazopanib of whom follow-up drug levels were measured between August 2012 and April 2016. Patients' characteristics were collected by reviewing electronic patient records. Drug levels were measured using high-performance liquid chromatography coupled with tandem mass spectrometry and trough levels were estimated using a predefined algorithm. Dose interventions were proposed based on trough levels., Results: In total, 396 trough levels were determined in 109 patients. Median sample frequency per patient was 3. During the first measurement only 38% of patients showed trough levels within the predefined target ranges despite standard dosing; 52% of the patients showed drug levels below and 10% above the target range. In 35 out of 41 patients (85%) dose interventions led to adequate trough levels. Eventually, 64% of the total cohort reached adequate trough levels., Conclusions: Dose optimization proved an effective tool to reach adequate trough levels in patients treated with imatinib, sunitinib and pazopanib. The percentage of patients with adequate trough levels increased from 38 to 64%. Therapeutic drug monitoring may add to the improvement of efficacy and reduction of toxicity and costs of these treatments., (© 2017 The British Pharmacological Society.)

Aims: In patients with diabetes treated with sunitinib symptomatic hypoglycaemia has been reported. To explore the mechanism of this adverse effect we performed a prospective study to investigate the effect of sunitinib on insulin concentration, insulin clearance and insulin sensitivity., Methods: We studied the early effects of sunitinib on insulin sensitivity and insulin clearance with a hyperinsulinaemic euglycaemic clamp (insulin infusion rate 60 mU m−2 min−1; steady-state 90–120 min) in patients with renal cell carcinoma before and 1 week after the start of sunitinib 50 mg day−1. Insulin sensitivity index (SI) was defined as steady-state glucose disposal divided by the steady-state plasma insulin., Results: Ten patients (one with diabetes, treated with metformin) were included in the study protocol. Steady-state insulin concentrations during the clamp increased after 1 week of sunitinib (from 128.9 ± 9.0 mU l−1 to 170.8 ± 12.8 mU l−1, P < 0.05; 95% CI on difference − 64.3, −19.6). The calculated insulin sensitivity index decreased from 0.22 ± 0.04 before to 0.18 ± 0.02 μmol kg−1 min−1 per mU l−1 insulin (P < 0.05; 95% CI on difference 0.07, 0.08). As the insulin infusion rate was similar for both clamps, the increased steady-state insulin concentration indicates reduced insulin clearance., Conclusion: Sunitinib affects insulin clearance which could possibly lead to overexposure to insulin in patients using insulin or insulin-secretion stimulating agents.