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Introduction and Objective: Pazopanib is registered for metastatic renal cell carcinoma and soft-tissue sarcoma (STS). Its variable pharmacokinetic (PK) characteristics and narrow therapeutic range provide a strong rationale for therapeutic drug monitoring (TDM). Prior studies have defined target levels of drug exposure (≥ 20.5 mg/L) linked to prolonged progression-free survival (PFS), but the added value of using TDM remains unclear. This study investigates the effect of TDM of pazopanib in patients with STS on survival outcomes and dose-limiting toxicities (DLTs) and evaluates the feasibility of TDM-guided dosing. Methods: A TDM-guided cohort was compared to a non-TDM-guided cohort for PFS, overall survival (OS) and DLTs. PK samples were available from all patients, though not acted upon in the non-TDM-guided cohort. We evaluated the feasibility of TDM by comparing the proportion of underdosed patients in our TDM cohort with data from previous publications. Results: A total of 122 STS patients were included in the TDM-guided cohort (n = 95) and non-TDM-guided cohort (n = 27). The average exposure in the overall population was 30.5 mg/L and was similar in both groups. Median PFS and OS did not differ between the TDM-guided cohort and non-TDM-guided cohort (respectively 5.5 vs 4.4 months, p = 0.3, and 12.6 vs 10.1 months, p = 0.8). Slightly more patients in the non-TDM-guided cohort experienced DLTs (54%) compared to the TDM-guided cohort (44%). The proportion of underdosed patients (13.3%) was halved compared to historical data (26.7%). Conclusion: TDM reduced the proportion of patients with subtherapeutic exposure levels by ~ 50%. Nonetheless, the added value of TDM for achieving target trough levels of ≥ 20.5 mg/L for pazopanib on survival outcomes could not be confirmed in STS patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant imatinib is considered for gastrointestinal stromal tumors (GISTs) when decreased tumor size provides less extensive surgery and higher R0 resection rates. This study evaluates the effectivity and safety of neoadjuvant imatinib for large or locally advanced GIST. Patients and Methods: From the prospective database of the Dutch GIST Consortium, all patients who underwent surgery after neoadjuvant imatinib at our center between 2009 and 2022 were selected. Independent and blinded assessment of surgical strategy was performed by two surgeons, based on anonymized computed tomography (CT) scans before and after neoadjuvant imatinib. Results: Of 113 patients that received neoadjuvant imatinib, 108 (95%) [mean age 61.6, standard deviation (SD) 11.5, 54% male] underwent a GIST resection. Of all GISTs, 67% was localized in the stomach and 25% in the duodenum or small intestine. In 74% of the patients with GIST, a KIT exon 11 mutation was found. Decreased tumor size was seen in 95 (88%) patients. Having a KIT exon 11 mutation [odds ratio (OR) 5.64, 95% confidence interval (CI) 1.67–19.1, p < 0.01] or not having a mutation (OR 0.19, 95% CI 0.04–0.89, p = 0.04) were positive and negative predictive values for partial response, respectively. In 55 (51%) patients, there was deescalation of surgical strategy after neoadjuvant imatinib. Surgical complications were documented in 16 (15%) patients (n = 8, grade II; n = 5, grade IIIa; n = 3, grade IIIb) and R0 resection was accomplished in 95 (89%) patients. The 5-year disease-free and overall survival were 80% and 91%, respectively. Conclusion: This study shows that neoadjuvant imatinib is effective and safe for patients with large or locally advanced GIST. [ABSTRACT FROM AUTHOR]

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

Purpose: Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of locally advanced and metastatic gastrointestinal stromal tumours (GISTs). Patients are experiencing prolonged survival but often at the expense of their health-related quality of life. It is not only the physical side effects that impact GIST patients’ daily lives but also the psychological and social challenges they have to deal with. This qualitative study aimed to explore the psychological and social life challenges of GIST patients with locally advanced and metastatic disease on ≥ 5 years TKI treatment. Methods: Semi-structured interviews with 15 locally advanced and/or metastatic GIST patients and 10 medical oncologists with experience of delivering care to this specific patient group were conducted. Thematic analysis was used to interpret the data. Results: Psychological challenges expressed by participants concerned fears, scanxiety, negative change in emotion and mood, doubts about their treatment and follow-up, living with uncertainty, lack of understanding from others or healthcare professionals, and constantly being reminded of their illness. Challenges regarding social health included financial difficulties, challenges in relationships, concerns about fertility and parenting, work, and impact on social activities. Conclusion: The reported psychological and social challenges can significantly hamper the overall quality of life of GIST patients. Some challenges were clearly underreported and hardly recognized by medical oncologist, as they may tend to focus on the physical side effects and clinical outcomes of treatment. Therefore, it is essential to take the patient’s perspective into account in research and clinical practice to ensure optimal care for this patient group. [ABSTRACT FROM AUTHOR]

Background: The etiology of cutaneous angiosarcoma (cAS) may be idiopathic (I-cAS), or arise secondary to radiotherapy (RT-cAS), in chronic lymphedema (ST-cAS), or related to UV exposure (UV-cAS). The aim of this study was to evaluate oncological outcomes of different cAS subtypes. Patients and Methods: Non-metastatic cAS patients, treated with surgery for primary disease with curative intent, were retrospectively analyzed for oncological outcome, including local recurrence (LR), distant metastases (DM), and overall survival (OS). Results: A total of 234 patients were identified; 60 I-cAS, 122 RT-cAS, 9 ST-cAS, and 43 UV-cAS. The majority was female (78%), the median age was 66 years (IQR 57–76 years), the median tumor size was 4.4 cm (IQR 2.5–7.0 cm), and most common site of disease was the breast (59%). Recurrence was identified in 66% (44% LR and/or 41% DM), with a median follow up of 26.5 months (IQR 12–60 months). The 5-year OS was estimated at 50%, LRFS at 47%, and DMFS at 50%. There was no significant difference in LR, DM, or OS between the subtypes. Age < 65 years and administration of radiotherapy (RT) were significantly associated with lower LR rates (HR 0.560, 95% CI 0.3373–0.840, p = 0.005 and HR 0.421, 95% CI 0.225–0.790, p = 0.007, respectively), however no prognostic factors were identified for development of DM. Development of DM, but not LR (p = 0.052), was significantly associated with decreased OS (HR 6.486, 95% CI 2.939–14.318 p < 0.001). Conclusion: We found no significant difference in oncological outcome between the different cAS subtypes. OS remains relatively poor, and RT is associated with lower LR rates. [ABSTRACT FROM AUTHOR]

Purpose: Using patient-reported outcomes in routine cancer care may improve health outcomes. However, a lack of information about which scores are problematic in specific populations can impede use. To facilitate interpretation of the European Organisation for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-C30), we identified cut-off scores that indicate need for support by comparing each scale to relevant items from the Supportive Care Needs Survey (SCNS-LF59) in a young adult (YA) population. Methods: We conducted a cross-sectional survey amongst YAs with cancer ages 25–39 at diagnosis. Participants completed the EORTC QLQ-C30 and SCNS-LF59. Patient, clinician and research experts matched supportive care needs from the SCNS-LF59 to quality of life domains of the EORTC QLQ-C30. We evaluated the EORTC QLQ-C30 domain score's ability to detect patients with need using receiver operator characteristic (ROC) analysis, calculating the area under the ROC curve and sensitivity and specificity for selected cut-offs. Cut-offs were chosen by maximising Youden's J statistic and ensuring sensitivity passed 0.70. Sensitivity analyses were conducted to examine the variability of the cut-off scores by treatment status. Results: Three hundred and forty-seven YAs took part in the survey. Six experts matched SCNS-LF59 items to ten EORTC QLQ-C30 domains. The AUC ranged from 0.78 to 0.87. Cut-offs selected ranged from 8 (Nausea and Vomiting and Pain) to 97 (Physical Functioning). All had adequate sensitivity (above 0.70) except the Financial Difficulties scale (0.64). Specificity ranged from 0.61 to 0.88. Four of the cut-off scores differed by treatment status. Conclusion: Cut-offs with adequate sensitivity were calculated for nine EORTC QLQ-C30 scales for use with YAs with cancer. Cut-offs are key to interpretability and use of the EORTC QLQ-C30 in routine care to identify patients with supportive care need. [ABSTRACT FROM AUTHOR]

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

Purpose: Angiosarcoma (AS) is a rare vasoformative sarcoma, with poor overall survival and a high need for novel treatment options. Clinically, AS consists of different subtypes, including AS related to previous UV exposure (UV AS) which could indicate susceptibility to DNA damage repair inhibition. We, therefore, investigated the presence of biomarkers PARP1 (poly(ADP-ribose)polymerase-1) and Schlafen-11 (SLFN11) in UV AS. Based on experiences in other sarcomas, we examined (combination) treatment of PARP inhibitor (PARPi) olaparib and temozolomide (TMZ) in UV AS cell lines. Methods: Previously collected UV AS (n = 47) and non-UV AS (n = 96) patient samples and two UV AS cell lines (MO-LAS and AS-M) were immunohistochemically assessed for PARP1 and SLFN11 expression. Both cell lines were treated with single agents PARPi olaparib and TMZ, and the combination treatment. Next, cell viability and treatment synergy were analyzed. In addition, effects on apoptosis and DNA damage were examined. Results: In 46/47 UV AS samples (98%), PARP1 expression was present. SLFN11 was expressed in 80% (37/46) of cases. Olaparib and TMZ combination treatment was synergistic in both cell lines, with significantly increased apoptosis compared to single agent treatment. Furthermore, a significant increase in DNA damage marker γH2AX was present in both cell lines after combination therapy. Conclusion: We showed combination treatment of olaparib with TMZ was synergistic in UV AS cell lines. Expression of PARP1 and SLFN11 was present in the majority of UV AS tumor samples. Together, these results suggest combination treatment of olaparib and TMZ is a potential novel AS subtype-specific treatment option for UV AS patients. [ABSTRACT FROM AUTHOR]

Purpose: Desmoplastic small round cell tumors (DSRCTs) are highly malignant and very rare soft tissue sarcomas with a high unmet need for new therapeutic options. Therefore, we examined poly(ADP-ribose) polymerase 1 (PARP1) and Schlafen-11 (SLFN11) expression in DSRCT tumor tissue and the combination of PARP inhibitor olaparib with the alkylating agent temozolomide (TMZ) in a preclinical DSRCT model. Methods: PARP1 and SLFN11 have been described as predictive biomarkers for response to PARP inhibition. Expression of PARP1 and SLFN11 was assessed in 16 and 12 DSRCT tumor tissue samples, respectively. Effects of single-agent olaparib, and olaparib and TMZ combination treatment were examined using the preclinical JN-DSRCT-1 model. In vitro, single-agent and combination treatment effects on cell viability, the cell cycle, DNA damage and apoptosis were examined. Olaparib and TMZ combination treatment was also assessed in vivo. Results: PARP1 and SLFN11 expression was observed in 100% and 92% of DSRCT tumor tissues, respectively. Olaparib treatment reduced cell viability and cell migration in a dose-dependent manner in vitro. Drug synergy between olaparib and TMZ was observed in vitro and in vivo. Combination treatment led to a cell-cycle arrest and induction of DNA damage and apoptosis, even when combined at low dosages. Conclusion: We show high PARP1 and SLFN11 expression in DSRCT tumor material and antitumor effects following olaparib and TMZ combination treatment in a preclinical DSRCT model. This suggests that olaparib and TMZ combination treatment could be a potential treatment option for DSRCTs. [ABSTRACT FROM AUTHOR]

Background: Autologous dendritic cell (DC) vaccines can induce tumor-specific T cells, but their effect can be counteracted by immunosuppressive mechanisms. Cisplatin has shown immunomodulatory effects in vivo which may enhance efficacy of DC vaccination. Methods: This is a prospective, randomized, open-label phase 2 study (NCT02285413) including stage III and IV melanoma patients receiving 3 biweekly vaccinations of gp100 and tyrosinase mRNA-loaded monocyte-derived DCs with or without cisplatin. Primary objectives were to study immunogenicity and feasibility, and secondary objectives were to assess toxicity and survival. Results: Twenty-two stage III and 32 stage IV melanoma patients were analyzed. Antigen-specific CD8+ T cells were found in 44% versus 67% and functional T cell responses in 28% versus 19% of skin-test infiltrating lymphocytes in patients receiving DC vaccination with and without cisplatin, respectively. Four patients stopped cisplatin because of toxicity and continued DC monotherapy. No therapy-related grade 3 or 4 adverse events occurred due to DC monotherapy. During combination therapy, one therapy-related grade 3 adverse event, decompensated heart failure due to fluid overload, occurred. The clinical outcome parameters did not clearly suggest significant differences. Conclusions: Combination of DC vaccination and cisplatin in melanoma patients is feasible and safe, but does not seem to result in more tumor-specific T cell responses or improved clinical outcome, when compared to DC vaccination monotherapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Knowledge of caregivers' burden and fatigue before and after patients' treatment for locally advanced head and neck cancer is scarce. Therefore, we aimed to explore caregivers' fatigue and burden in relation to patients' fatigue, distress, and quality of life.Methods: For caregivers, burden and fatigue were assessed. For patients, fatigue severity, distress, and health-related quality of life (HRQoL) were assessed. Measurements were conducted prior to treatment, 1 week, and 3 months after chemoradiotherapy.Results: Caregivers' burden and fatigue followed patients' high peak in distress, fatigue, and diminished HRQoL as a consequence of treatment. Caregivers' baseline fatigue was a predictor for fatigue after chemoradiotherapy. Female spouses with higher baseline levels of fatigue and burden and caring for patients with lower levels of HRQoL seem risk factors for burden after chemoradiotherapy.Conclusions: Attention should be paid to caregivers' burden and fatigue before starting patients' intense treatment with chemoradiotherapy, as both burden and fatigue before starting treatment may contribute to burden and fatigue after chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Purpose: The main objective of this preliminary analysis of the IMaging PAtients for Cancer drug selecTion (IMPACT)-renal cell cancer (RCC) study is to evaluate the lesion detection of baseline contrast-enhanced CT, [89Zr]Zr-DFO-girentuximab-PET/CT and [18F]FDG-PET/CT in detecting ccRCC lesions in patients with a good or intermediate prognosis metastatic clear cell renal cell carcinoma (mccRCC) according to the International Metastatic Database Consortium (IMDC) risk model. Methods: Between February 2015 and March 2018, 42 newly diagnosed mccRCC patients with good or intermediate prognosis, eligible for watchful waiting, were included. Patients underwent CT, [89Zr]Zr-DFO-girentuximab-PET/CT and [18F]FDG-PET/CT at baseline. Scans were independently reviewed and lesions of ≥10 mm and lymph nodes of ≥15 mm at CT were analyzed. For lesions with [89Zr]Zr-DFO-girentuximab or [18F]FDG-uptake visually exceeding background uptake, maximum standardized uptake values (SUVmax) were measured. Results: A total of 449 lesions were detected by ≥1 modality (median per patient: 7; ICR 4.25–12.75) of which 42% were in lung, 22% in lymph nodes and 10% in bone. Combined [89Zr]Zr-DFO-girentuximab-PET/CT and CT detected more lesions than CT alone: 91% (95%CI: 87–94) versus 56% (95%CI: 50–62, p = 0.001), respectively, and more than CT and [18F]FDG-PET/CT combined (84% (95%CI:79–88, p < 0.005). Both PET/CTs detected more bone and soft tissue lesions compared to CT alone. Conclusions: The addition of [89Zr]Zr-DFO-girentuximab-PET/CT and [18F]FDG-PET/CT to CT increases lesion detection compared to CT alone in newly diagnosed good and intermediate prognosis mccRCC patients eligible for watchful waiting. [ABSTRACT FROM AUTHOR]

Purpose: Desmoid fibromatosis (DF) is a rare, unpredictable disease with no established, evidence-based treatments. Individual management is based on consensus algorithms. This study aimed to examine the specific health-related quality of life challenges faced by DF patients, current experiences and expectations of care.Methods: Twenty-seven DF patients were purposively sampled from The Royal Marsden Hospital. Two focus groups and 13 interviews (males 12, females 15; mean age at study 39.5 years) explored health-related quality of life issues and experiences of healthcare. Thematic content was analysed.Results: Discussions revealed four key themes (diagnostic pathway; treatment pathway; living with DF; supportive care). Diagnostic delay resulted from lack of recognition by patients and healthcare professionals. Some patients received an initial diagnosis of cancer, causing significant distress. Treatment decisions were challenging, and patients experienced uncertainty among clinicians about optimal therapies. Side-effects of treatment were severe, including fatigue, nausea, anorexia, low libido and depression. Pain was the most debilitating symptom and dependency on painkillers was a significant concern. Functional limitation and restricted mobility frequently affected daily activities. Patients experienced difficulty accomplishing their role in society; relationship problems, caring for children, employment and financial difficulties. Social isolation and lack of understanding were common. The psychological impact of this "life-changing and life-long" condition was profound. All patients requested knowledgeable healthcare professionals, more information, continuity of care and peer support.Conclusions: DF patients face complex physical, psychological and practical challenges. Comprehensive care services are needed. Increasing awareness may help to improve diagnostic pathways and overall patient experience. [ABSTRACT FROM AUTHOR]

Purpose: Sporadic desmoid-type fibromatosis (DTF) is a rare, chronic, non-metastasising, disease of the soft tissues. It is characterised by local invasive and unpredictable growth behaviour and a high propensity of local recurrence after surgery thereby often having a great impact on health-related quality of life (HRQL). This study aims to review currently used HRQL measures and to asses HRQL issues among DTF patients.Methods: A mixed methods methodology was used consisting of (1) a systematic literature review, according to the PRISMA guidelines (2009), using search terms related to sporadic DTF and HRQL in commonly used databases (e.g. Embase, Medline Ovid, Web of science, Cochrane Central, Psyc Info, and Google scholar), to provide an overview of measures previously used to evaluate HRQL among DTF patients; (2) focus groups to gain insight into HRQL issues experienced by DTF patients.Results: The search strategy identified thirteen articles reporting HRQL measures using a wide variety of cancer-specific HRQL tools, functional scores, symptom scales (e.g. NRS), and single-item outcomes (e.g. pain and functional impairment). No DTF-specific HRQL tool was found. Qualitative analysis of three focus groups (6 males, 9 females) showed that participants emphasised the negative impact of DTF and/or its treatment on several HRQL domains. Six themes were identified: (1) diagnosis, (2) treatment, (3) follow-up and recurrence, (4) physical domain, (5) psychological and emotional domain, and (6) social domain.Conclusion: A DTF-specific HRQL tool and consensus regarding the preferred measurement tool among DTF patients is lacking. Our study indicates that HRQL of DTF patients was negatively affected in several domains. A DTF-specific HRQL measure could improve our understanding of short- and long-term effects and, ideally, can be used in both clinic and for research purposes. [ABSTRACT FROM AUTHOR]

Objective: High fear of cancer recurrence (FCR) is a frequently reported problem among cancer patients. Previous research has shown that younger age is associated with higher levels of FCR. However, little attention has been given to date about how FCR manifests itself among adolescent and young adult (AYA) cancer patients. This study explores the prevalence, correlates of high FCR, and its association with HRQoL in cancer patients in their late adolescence or young adulthood.Methods: Seventy-three AYA cancer patients, aged 18-35 years at diagnosis, consulted the AYA team of the Radboud University Medical Center completed questionnaires including the Cancer Worry Scale (CWS), Quality of Life-Cancer Survivors (QOL-CS), and Hospital Anxiety and Depression Scale (HADS). Sociodemographic and medical data was collected by self-reported questionnaire.Results: Forty-five participants experienced high FCR (62%), which was higher than the 31-52% reported in previous studies among mixed adult cancer patient samples. Sociodemographic and medical variables were not associated with levels of FCR. High FCR was significantly associated with lower levels of social and psychological functioning and overall HRQoL and higher levels of anxiety and psychological distress.Conclusion: Results illustrate that FCR is a significant problem among AYA cancer patients consulting an AYA team, with participants reporting higher levels of FCR than cancer patients of mixed ages. Health care providers should pay specific attention to this problem by screening and the provision of appropriate psychosocial care when needed. [ABSTRACT FROM AUTHOR]

Purpose: The CONDOR study showed that docetaxel/cisplatin/5-fluorouracil (TPF) followed by conventional radiotherapy with cisplatin 100 mg/m2 on days 1, 22, and 43 (cis100 + RT; n = 27)) versus accelerated radiotherapy with cisplatin weekly 40 mg/m2 (cis40 + ART; n = 29) in locally advanced head and neck cancer (LAHNC) patients was not feasible. Here, we report the analysis of health-related quality of life (HRQOL) of the patients entered in this study.Methods: HRQOL was assessed at baseline, after two TPF, before start of chemoradiotherapy, and 1, 4, 8, 12, and 24 months after completion of chemoradiotherapy using the EORTC-QLQ-C30 and QLQ-H&N35 in 62 patients.Results: Compliance with the QOL questionnaires was 94% (59/62) at baseline and 61% (30/49) at 12 months, respectively. HRQOL decreased after TPF and further decreased during chemoradiohteray in both arms equally. Pain and swallowing dysfunction improved significantly during TPF but deteriorated below baseline levels during chemoradiotherapy, cis40 + ART > cis100 + RT (p < 0.05). HRQOL and symptoms restored to baseline within 12 months in both arms and remained at that level until 24 months.Conclusions: After TPF, cis40 + ART had a larger negative impact on symptoms than cis100 + RT, probably due to the ART. HRQOL and symptoms restored to baseline levels within 12 months after end of treatment in both arms, which is an important perspective for patients during the phase of most serious acute side effects of treatment.Trial Registration: NCT00774319. [ABSTRACT FROM AUTHOR]

Background: The receptor tyrosine kinase (RTK) anaplastic lymphoma kinase (ALK) has been implicated in the tumorigenesis of rhabdomyosarcoma (RMS). However, the exact role of ALK in RMS is debatable and remains to be elucidated.Objective: To determine the in vitro and in vivo effects and mechanism of action of the second-generation ALK inhibitor ceritinib on RMS cell growth.Methods: Effects of ceritinib on cell proliferation, wound healing, cell cycle, and RTK signaling were determined in alveolar and embryonal rhabdomyosarcoma (ARMS, ERMS). In addition, possible synergistic effects of combined treatment with ceritinib and the Abl/Src family kinase inhibitor dasatinib were determined.Results: Ceritinib treatment led to decreased cell proliferation, cell cycle arrest, apoptosis, and decreased in vivo tumor growth for the ARMS subtype. ERMS cell lines were less affected and showed no cell cycle arrest or apoptosis. Both subtypes lacked intrinsic ALK phosphorylation, and ceritinib was shown to affect the IGF1R signaling pathway. High levels of phosphorylated Src (Tyr416) were present following ceritinib treatment, making combined treatment with a Src inhibitor a potential treatment option. Combined treatment of ceritinib and dasatinib showed synergistic effects in both ERMS and ARMS cell lines.Conclusion: This study shows that monotherapy with an ALK inhibitor, such as ceritinib, in RMS, has no effect on ALK signaling. However, the synergistic effects of ceritinib and dasatinib are promising, most probably due to targeting of IGF1R and Src. [ABSTRACT FROM AUTHOR]

Purpose: The current study determined the prevalence of severe fatigue in adolescent and young adult (AYA) cancer patients (aged 18-35 years at diagnosis) consulting a multidisciplinary AYA team in comparison with gender- and age-matched population-based controls. In addition, impact of severe fatigue on quality of life and correlates of fatigue severity were examined.Methods: AYAs with cancer (n = 83) completed questionnaires including the Checklist Individual Strength (CIS-fatigue), Quality of Life (QoL)-Cancer Survivor, Hospital Anxiety and Depression Scale (reflecting psychological distress), and the Cancer Worry Scale (reflecting fear of cancer recurrence or progression).Results: The vast majority of participants had been treated with chemotherapy (87%) and had no active treatment at the time of participation (73.5%). Prevalence of severe fatigue (CIS-fatigue score ≥35) in AYAs with cancer (48%, n = 40/83) was significantly higher in comparison with matched population-based controls (20%, n = 49/249; p < .001). Severely fatigued AYAs with cancer reported lower QoL compared to non-severely fatigued AYAs with cancer (p < .05). Female gender, being unemployed, higher disease stage (III-IV) at diagnosis, receiving active treatment at the time of study participation, being treated with palliative intent, having had radiotherapy, higher fear of recurrence or progression, and higher psychological distress were significantly correlated with fatigue severity (p < .05).Conclusions: Severe fatigue based on a validated cut-off score was highly prevalent in this group of AYAs with cancer. QoL is significantly affected by severe fatigue, stressing the importance of detection and management of this symptom in those patients affected by a life-changing diagnosis of cancer in late adolescence or young adulthood. [ABSTRACT FROM AUTHOR]

Purpose: In order to understand the multidimensional mechanism of fear of cancer recurrence (FCR) and to identify potential targets for interventions, it is important to empirically test the theoretical model of FCR. This study aims at assessing the validity of Lee-Jones et al.'s FCR model.Methods: A total of 1205 breast cancer survivors were invited to participate in this study. Participants received a questionnaire booklet including questionnaires on demographics and psychosocial variables including FCR. Data analysis consisted of the estimation of direct and indirect effects in mediator models.Results: A total of 460 women (38 %) participated in the study. Median age was 55.8 years (range 32-87). Indirect effects of external and internal cues via FCR were found for all mediation models with limited planning for the future (R 2 = .28) and body checking (R 2 = .11-.15) as behavioral response variables, with the largest effects for limited planning for the future. A direct relation was found between feeling sick and seeking professional advice, not mediated by FCR.Conclusions: In the first tested models of FCR, all internal and external cues were associated with higher FCR. In the models with limited planning for the future and body checking as behavioral response, an indirect effect of cues via FCR was found supporting the theoretical model of Lee-Jones et al.Implications For Cancer Survivors: An evidence-based model of FCR may facilitate the development of appropriate interventions to manage FCR in breast cancer survivors. [ABSTRACT FROM AUTHOR]

Communication about palliative treatment options requires a balance between providing patients with sufficient information and not providing unwanted information. Surveys have indicated that many patients with advanced cancer express a wish to receive detailed information. In this prospective multicenter study, the information desire of patients with advanced breast or colorectal cancer was further investigated by offering treatment-related information to patients using a decision aid (DA). In addition, this study explored oncologists' awareness of their patients' information desire. Seventy-seven patients with advanced breast or colorectal cancer facing the decision whether to start second-line palliative chemotherapy were offered a DA by a nurse. This DA contained information on adverse events, tumor response, and survival. The nurse asked the patient whether each information item was desired. Ninety-five percent of patients chose to receive information on adverse events, 91 % chose to receive information on tumor response, and 74 % chose to receive information on survival. Oncologists' judgment of patients' information desire was 100, 97, and 81 %, respectively. For all three information items together, oncologists correctly judged the information desire of 62 % of patients. This study confirms that many patients with advanced cancer wish to receive detailed information on the benefits and risks of palliative treatment options when the information is actually available. Oncologists were adequately aware of this high information desire, but had some difficulty judging the information desire of individual patients. A stepped approach to giving information ("preview, ask, tell, ask") may help to better meet patients' information needs. [ABSTRACT FROM AUTHOR]

Purpose: Fatigue is a frequently reported symptom by patients with advanced cancer, but hardly any prospective information is available about fatigue while on treatment in the palliative setting. In a previous cross-sectional study, we found several factors contributing to fatigue in these patients. In this study, we investigated the course of fatigue over time and if psychosocial factors were associated with fatigue over time.Methods: Patients on cancer treatment for incurable solid tumors were observed over 6 months. Patients filled in the Checklist Individual Strength monthly to measure the course of fatigue. Baseline questionnaires were used to measure disease acceptance, anxiety, depressive mood, fatigue catastrophizing, sleeping problems, discrepancies in social support, and self-reported physical activity for their relation with fatigue over time.Results: At baseline 137 patients and after 6 months 89 patients participated. The mean duration of participation was 4.9 months. At most time points, fatigue scores were significantly higher in the group dropouts in comparison with the group participating 6 months (completers). Overall fatigue levels remained stable over time for the majority of participants. In the completers, 42% never experienced severe fatigue, 29% persisted being severely fatigued, and others had either an increasing or decreasing level. Of the investigated factors, low reported physical activity and non-acceptance of cancer were associated significantly to fatigue.Conclusion: A substantial number of participants never experienced severe fatigue and fatigue levels remained stable over time. For those who do experience severe fatigue, non-acceptance of having incurable cancer and low self-reported physical activity may be fatigue-perpetuating factors. [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]

Purpose: This work aims to prospectively study stress response symptoms (SRS) in adolescents during the first year after a parent's cancer diagnosis and factors associated with SRS. Additionally, SRS in these adolescents were compared to SRS in adolescents whose parents were diagnosed 1-5 years (reference group) previously.Methods: Forty-nine adolescents, 37 ill parents, and 37 spouses completed questionnaires within 4 months after diagnosis (T1) and six (T2) and 12 months (T3) later.Results: Clinically elevated SRS were found in 29% of adolescents at T1, 16% at T2, and 14% at T3. In contrast, in the reference group, we found 29% clinically elevated SRS. Daughters seemed more at risk than sons. Adolescents' age, patient's gender, and intensity and duration of treatment did not significantly affect SRS. Adolescents with more SRS reported having more emotional/behavioral problems. Parents observed fewer problems in those adolescents. Initial SRS affected later SRS and emotional problems.Conclusions: The findings illustrate that adolescent children of cancer patients may have clinically elevated SRS that are associated with emotional and behavioral problems. The prevalence of such problems may be underestimated by the parents. [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]

Multidrug resistance associated proteins (MRPs) and P-glycoprotein (P-gp) are involved in hepatobiliary transport of various compounds. Our aim was (1) to define transporter specificity of the cholescintigraphic agents99mTc-HIDA and99mTc-MIBI, which are used clinically for myocardial perfusion measurements; and (2) to deduce MRP and P-gp functions in vivo from hepatic99mTc kinetics. Accumulation of radioactivity was measured in the human tumor cell lines GLC4, GLC4/ADR150x (MRP1-overexpressing/P-gp-negative) and GLC4/P-gp (P-gp-overexpressing). Bile secretion was quantified in untreated and in glutathione-depleted control and MRP2-deficient (GY/TR-) rats. Hepatobiliary transport was measured using a gamma camera in both types of rats.99mTc-HIDA accumulated 5.8-fold less in GLC4/ADR150x calls than in GLC4 or GLC4/P-gp cells. In GLC4/ADR150x, the cellular99mTc-HIDA content was increased 3.4-fold by the MRP1,2 inhibitor MK571 (50 µM), while MK571 had no measurable effect in GLC4 and GLC4/P-gp cells.99mTc-MIBI accumulated less in GLC4/P-gp and GLC4/ADR150x cells than in GLC4 cells. Bile secretion of99mTc-HIDA was impaired in GY/TR- compared to control rats and not affected by glutathione depletion in GY/TR- rats. Hepatic secretion of99mTc-HIDA was slower in GY/TR- (t1/2 40 min) than in control rats (t1/2 7 min). Bile secretion of99mTc-MIBI was similar in both rat strains and impaired by glutathione depletion in control rats only, indicating compensatory activity of additional transporter(s) in GY/TR- rats.99mTc-HIDA is transported only by MRP1,2 only, while99mTc-MIBI is transported by P-gp and MRP1,2. The results indicate that hepatic P-gp and MRP1,2 function can be assessed in vivo by sequential use of both radiopharmaceuticals. [ABSTRACT FROM AUTHOR]

Objective. Cancer patients with febrile neutropenia after chemotherapy have a variable risk of bacterial infection. Especially Gram-negative bacteremia is associated with high mortality and/or morbidity. Early diagnosis of patients with Gram-negative bacteremia at the onset of febrile neutropenia is potentially useful in tailoring therapy. Design and setting. Prospective study at the Department of Pediatric Oncology and Internal Medicine of a university hospital. Patients. Were analyzed 66 febrile neutropenic episodes in 57 adults and children. Patients were divided into four groups: those with Gram-negative bacteremia, Gram-positive bacteremia, clinical sepsis, or fever of unknown origin. Measurements and results. Plasma lipopolysaccharide-binding protein (LBP) and C-reactive protein (CRP) concentrations were determined. LBP at the onset of febrile neutropenia was significantly higher in patients with Gram-negative bacteremia than those with fever of unknown origin and those with Gram-positive bacteremia. Using a cutoff value for LBP proved to have much greater sensitivity, specificity, and positive and negative predictive value for Gram-negative bacteremia than the best cutoff value for CRP. Conclusions. An initial high LBP level might predict Gram-negative bacteremia in cancer patients with febrile neutropenia. These results may have potential clinical impact by allowing therapy to be initiated for these patients at a very early stage. [ABSTRACT FROM AUTHOR]

In this article the authors discuss molecular imaging of tumors. They note how targeted treatments substantially change oncology such as the result of disease stabilization than tumor shrinkage. Moreover, they mention the need of molecular imaging such as positron emission tomography (PET) to provide clinically relevant information. An overview of a study on the systemic cytotoxic monitoring and targeted therapy is offered.

The article presents a correction to a report on "Prevalence and impact of severe fatigue in adolescent and young adult cancer patients in comparison with population-based controls" published in a previous issue of 2017.

Background: Sclerosing epithelioid fibrosarcoma (SEF) is a very rare soft tissue sarcoma subtype. Clinically it is an aggressive tumour; however, to our knowledge there are no published reports regarding the efficacy of chemotherapy in SEF. Therefore, the aim of this study was to document the outcome of a series of patients with SEF treated at a single referral centre with reference to systemic therapy.Methods: A retrospective search of a prospectively maintained database was performed to identify all patients diagnosed with SEF between 1990 and 2017. The diagnosis was confirmed in each case by a dedicated soft tissue sarcoma pathologist. We analysed those with recurrent disease and the effect of systemic chemotherapy in the metastatic setting.Results: Thirteen patients were identified, median overall survival from diagnosis and metastasis were 47.3 (95% CI 25.0-131.9) and 16.3 (95% CI 5.3-20.6) months, respectively. In total, 12 (92.3%) patients developed metastatic disease of which 10 died of disease, 1 was lost to follow-up and 1 had recently commenced palliative treatment. Among the 10 patients with metastatic disease, 7 received palliative chemotherapy. Palliative chemotherapy resulted in partial response in 1 patient, stable disease in 3 patients and progressive disease in 3 patients. Median time to disease progression was 2.7 (95% CI 1.2-4.4) months. Two of 13 patients were treated with adjuvant chemotherapy, receiving 6 cycles of liposomal doxorubicin and 1 cycle of doxorubicin, respectively, with a metastasis-free survival of 28.2 and 7.1 months, respectively.Conclusion: SEF is an aggressive sarcoma subtype with a poor outcome and with limited responsiveness to conventional chemotherapy. Patients with this subtype should be considered for participation in clinical trials with novel agents. Further investigation into the biology of this rare disease is required to improve outcomes. [ABSTRACT FROM AUTHOR]

Opinion Statement: Synovial sarcoma (SS) is a rare, yet highly malignant, type of soft tissue sarcoma (STS), for which survival has not improved significantly during the past years. In this review, we focus on systemic treatment in adults. Compared to other STS, SS are relatively chemosensitive. Ifosfamide and ifosfamide combinations are active in different lines of treatment. In high-risk extremity and chest wall STS, neoadjuvant doxorubicin and ifosfamide has shown as much activity as high-dose ifosfamide. There are indications that combination chemotherapy with doxorubicin and ifosfamide in this setting improves outcome. In the first-line metastatic setting, combination treatment with doxorubicin and ifosfamide is a preferred option in fit patients, while in other patients, sequential doxorubicin and ifosfamide can be considered. In second and later lines, pazopanib and trabectedin have shown activity. Many new approaches to treat metastatic SS are currently under investigation, both preclinical as well as clinical, including other receptor tyrosine kinase inhibitors, epigenetic modulators, compounds interfering with DNA damage response (DDR), and immunotherapy. [ABSTRACT FROM AUTHOR]