Summary Survival outcomes for adolescent and young adult patients with soft tissue sarcomas lag behind those of children diagnosed with histologically similar tumours. To help understand these ...differences in outcomes, we discuss the following issues with regard to the management of these patients with soft tissue sarcomas: delays in diagnosis, trial availability and participation, aspects of the organisation of care (with an emphasis on age-specific needs), national centralisation of sarcoma care, international consortia, and factors related to tumour biology. Improved understanding of the causes of the survival gap between adolescents and young adults with sarcomas will help drive new initiatives to improve final health outcomes in these populations. In this Review, we specifically focus on embryonal and alveolar rhabdomyosarcoma, synovial sarcoma, and adult soft tissue sarcomas diagnosed in adolescents and young adults, and discuss the age-specific needs of these patients.
Worldwide, more than 1.2 million adolescents and young adults (AYAs; those aged 15–39 years) are diagnosed with cancer each year. Although considerable variability exists according to cancer site and ...stage of disease, the 5-year relative survival at the time of diagnosis has been estimated at >80% for all AYA patients with cancer combined. Extensive survivorship research in recent decades has focused on patients diagnosed with cancer as children (<15 years) and older adults (>39 years), yet few studies to date have reported outcomes specifically for patients diagnosed as AYAs. With increasing incidence and improving survival for many tumor types, leading to the majority of AYA patients with cancer becoming long-term survivors, there is a critical need for research efforts to inform the survivorship care of this growing population. This article describes the population of AYA cancer survivors according to their epidemiology and late and long-term effects, the challenges and models of AYA survivorship care, as well as future opportunities for research and healthcare.
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.
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.
Summary Background Effective targeted treatment is unavailable for most sarcomas and doxorubicin and ifosfamide—which have been used to treat soft-tissue sarcoma for more than 30 years—still have an ...important role. Whether doxorubicin alone or the combination of doxorubicin and ifosfamide should be used routinely is still controversial. We assessed whether dose intensification of doxorubicin with ifosfamide improves survival of patients with advanced soft-tissue sarcoma compared with doxorubicin alone. Methods We did this phase 3 randomised controlled trial (EORTC 62012) at 38 hospitals in ten countries. We included patients with locally advanced, unresectable, or metastatic high-grade soft-tissue sarcoma, age 18–60 years with a WHO performance status of 0 or 1. They were randomly assigned (1:1) by the minimisation method to either doxorubicin (75 mg/m2 by intravenous bolus on day 1 or 72 h continuous intravenous infusion) or intensified doxorubicin (75 mg/m2 ; 25 mg/m2 per day, days 1–3) plus ifosfamide (10 g/m2 over 4 days with mesna and pegfilgrastim) as first-line treatment. Randomisation was stratified by centre, performance status (0 vs 1), age (<50 vs ≥50 years), presence of liver metastases, and histopathological grade (2 vs 3). Patients were treated every 3 weeks till progression or unacceptable toxic effects for up to six cycles. The primary endpoint was overall survival in the intention-to-treat population. The trial is registered with ClinicalTrials.gov , number NCT00061984. Findings Between April 30, 2003, and May 25, 2010, 228 patients were randomly assigned to receive doxorubicin and 227 to receive doxorubicin and ifosfamide. Median follow-up was 56 months (IQR 31–77) in the doxorubicin only group and 59 months (36–72) in the combination group. There was no significant difference in overall survival between groups (median overall survival 12·8 months 95·5% CI 10·5–14·3 in the doxorubicin group vs 14·3 months 12·5–16·5 in the doxorubicin and ifosfamide group; hazard ratio HR 0·83 95·5% CI 0·67–1·03; stratified log-rank test p=0·076). Median progression-free survival was significantly higher for the doxorubicin and ifosfamide group (7·4 months 95% CI 6·6–8·3) than for the doxorubicin group (4·6 months 2·9–5·6; HR 0·74 95% CI 0·60–0·90, stratified log-rank test p=0·003). More patients in the doxorubicin and ifosfamide group than in the doxorubicin group had an overall response (60 26% of 227 patients vs 31 14% of 228; p<0·0006). The most common grade 3 and 4 toxic effects—which were all more common with doxorubicin and ifosfamide than with doxorubicin alone—were leucopenia (97 43% of 224 patients vs 40 18% of 223 patients), neutropenia (93 42% vs 83 37%), febrile neutropenia (103 (46%) vs 30 13%), anaemia (78 35% vs 10 5%), and thrombocytopenia (75 33%) vs one <1%). Interpretation Our results do not support the use of intensified doxorubicin and ifosfamide for palliation of advanced soft-tissue sarcoma unless the specific goal is tumour shrinkage. These findings should help individualise the care of patients with this disease. Funding Cancer Research UK, EORTC Charitable Trust, UK NHS, Canadian Cancer Society Research Institute, Amgen.
Co‐treatment with gastric acid suppressants (GAS) in patients taking anticancer drugs that exhibit pH‐dependant absorption may lead to decreased drug exposure and may hamper drug efficacy. In our ...study, we investigated whether a 1‐hour time interval between subsequent intake of pazopanib and GAS could mitigate this negative effect on drug exposure. We performed an observational study in which we collected the first steady‐state pazopanib trough concentration (Cmin) levels from patients treated with pazopanib 800 mg once daily (OD) taken fasted or pazopanib 600 mg OD taken with food. All patients were advised to take GAS 1 hour after pazopanib. Patients were grouped based on the use of GAS and the geometric (GM) Cmin levels were compared between groups for each dose regimen. Additionally, the percentage of patients with exposure below the target threshold of 20.5 mg/L and the effect of the type of PPI was explored. The GM Cmin levels were lower in GAS users vs non‐GAS users for both the 800 and 600 mg cohorts (23.7 mg/L 95% confidence interval CI: 21.1‐26.7 vs 28.2 mg/L 95% CI: 25.9‐30.5, P = .015 and 26.0 mg/L 95% CI: 22.4‐30.3 vs 33.5 mg/L 95% CI: 30.3‐37.1, P = .006). Subtherapeutic exposure was more prevalent in GAS users vs non‐GAS users (33.3% vs 19.5% and 29.6% vs 14%). Sub‐analysis showed lower GM pazopanib Cmin in patients who received omeprazole, while minimal difference was observed in those receiving pantoprazole compared to non‐users. Our research showed that a 1‐hour time interval between intake of pazopanib and GAS did not mitigate the negative effect of GAS on pazopanib exposure and may hamper pazopanib efficacy.
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.
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.
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