Associations between diagnostic time intervals and health-related quality of life, clinical anxiety and depression in adolescents and young adults with cancer: cross-sectional analysis of the BRIGHTLIGHT cohort.

BACKGROUND: The association of diagnostic intervals and outcomes is poorly understood in adolescents and young adults with cancer (AYA). We investigated associations between diagnostic intervals and health-related quality of life (HRQoL), anxiety and depression in a large AYA cohort. METHODS: Participants aged 12-24 completed interviews post-diagnosis, providing data on diagnostic experiences and the patient-reported outcomes (PROs) HRQoL, anxiety and depression. Demographic and cancer information were obtained from clinical and national records. Six diagnostic intervals were considered. Relationships between intervals and PROs were examined using regression models. RESULTS: Eight hundred and thirty participants completed interviews. In adjusted models, across 28 of 30 associations, longer intervals were associated with poorer PROs. Patient intervals (symptom onset to first seeing a GP) of ≥1 month were associated with greater depression (adjusted odds ratio (aOR):1.7, 95% Confidence Interval (CI):1.1-2.5) compared to <1 month. ≥3 pre-referral GP consultations were associated with greater anxiety (aOR:1.6, CI:1.1-2.3) compared to 1-2 consultations. Symptom onset to first oncology appointment intervals of ≥2 months was associated with impaired HRQoL (aOR:1.8, CI:1.2-2.5) compared to <2 months. CONCLUSIONS: Prolonged diagnostic intervals in AYA are associated with an increased risk of impaired HRQoL, anxiety and depression. Identifying and delivering interventions for this high-risk group is a priority.

SARC025 arms 1 and 2: A phase 1 study of the poly(ADP-ribose) polymerase inhibitor niraparib with temozolomide or irinotecan in patients with advanced Ewing sarcoma.

BACKGROUND: In preclinical Ewing sarcoma (ES) models, poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors were identified as a potential therapeutic strategy with synergy in combination with cytotoxic agents. This study evaluated the safety and dosing of the PARP1/2 inhibitor niraparib (NIR) with temozolomide (TMZ; arm 1) or irinotecan (IRN; arm 2) in patients with pretreated ES. METHODS: Eligible patients in arm 1 received continuous NIR daily and escalating TMZ (days 2-6 [D2-6]) in cohort A. Subsequent patients received intermittent NIR dosing (cohort B), with TMZ re-escalation in cohort C. In arm 2, patients were assigned to NIR (days 1-7 [D1-7]) and escalating doses of IRN (D2-6). RESULTS: From July 2014 to May 2018, 29 eligible patients (23 males and 6 females) were enrolled in arms 1 and 2, which had 7 dose levels combined. Five patients experienced at least 1 dose-limiting toxicity (DLT) in arm 1 (grade 4 [G4] neutropenia for >7 days or G4 thrombocytopenia), and 3 patients experienced at least 1 DLT in arm 2 (grade 3 [G3] colitis, G3 anorexia, or G3 alanine aminotransferase elevation). The maximum tolerated dose was NIR at 200 mg every day on D1-7 plus TMZ at 30 mg/m2 every day on D2-6 (arm 1) or NIR at 100 mg every day on D1-7 plus IRN at 20 mg/m2 every day on D2-6 (arm 2). One confirmed partial response was observed in arm 2; the median progression-free survival was 9.0 weeks (95% CI, 7.0-10.1 weeks) and 16.3 weeks (95% CI, 5.1-69.7 weeks) in arms 1 and 2, respectively. The median decrease in tumor poly(ADP-ribose) activity was 89% (range, 83%-98%). CONCLUSIONS: The combination of NIR and TMZ or IRN was tolerable, but at lower doses in comparison with conventional cytotoxic combinations. A triple-combination study of NIR, IRN, and TMZ has commenced.

Development of a patient-reported experience questionnaire for patients with sarcoma: the Sarcoma Assessment Measure (SAM).

PURPOSE: The aim of the study was to develop a patient-reported outcome measure for patients with sarcoma-the Sarcoma Assessment Measure (SAM). METHODS AND RESULTS: The systematic development of SAM included a three-stage, mixed-methods study using semi-structured interviews, focus groups and questionnaires, with all stages involving patients from across the United Kingdom. In-depth interviews were conducted with 121 patients (50% male; aged 13-82; with soft tissue sarcoma (62%), bone tumours (28%) and gastrointestinal stromal tumours (10%)). Content analysis of the interview transcripts identified 1415 post-diagnosis experience statements. Experience statements were reviewed, repetition was removed and sentences were refined to form 395 'items' which were included in an Item Reduction Questionnaire (IRQ) grouped as physical, emotional, social and financial wellbeing and sexuality. The IRQ was completed by 250 patients who rated each item on importance and worry. Items with a mean score above 5 (6 in the emotional domain) were removed, which reduced the list to 166 items. After review by the research team, 23 clinicians and 34 patients, 66 items were retained to test content validity. Items with a content validity ratio of < .33 were removed. Cognitive interviews were conducted with 10 patients on the final 22 items to test comprehension. Minor changes were made to four. CONCLUSION: SAM comprises of 22 items reflecting physical, emotional, social, financial wellbeing and sexuality. This systematic process of using patient experience to develop the content of SAM will ensure that it measures what is important to patients.

Current questions in bone sarcomas.

PURPOSE OF REVIEW: Osteosarcoma and Ewing sarcoma, the most common primary bone tumours in young people, are curable in most patients. However, these tumours remain a significant challenge due to the complexity and intensity of treatment and its long-term morbidity and the significant proportion of patients in whom treatment is unsuccessful. This review addresses questions about current management and emerging therapeutic targets for patients with osteosarcoma, Ewing sarcoma and chondrosarcoma, the commonest bone sarcoma but more common in older patients. RECENT FINDINGS: The largest collaborative international study in osteosarcoma, EURAMOS-1 determined that treatment of patients with resectable disease should not be altered on basis of pathological response to neoadjuvant chemotherapy. In view of little improvement in outcome being evident in recent years, novel therapeutic approaches are required. Putative targets and clinical trials of novel agents are discussed, including emerging targets such as poly (ADP-ribose) polymerase inhibition and isocitrate dehydrogenase inhibition in Ewing sarcoma and chondrosarcoma, respectively. Newer radiotherapy techniques including proton beam and particle ion therapy may be important for local tumour control in selected patients. SUMMARY: Collaborative studies are essential to answer current questions and investigate novel therapies in these malignancies to improve outcome and quality of life for patients.

Follow-up practices for high-grade extremity Osteosarcoma.

BACKGROUND: The optimal conduct of follow-up (FU) of patients with osteosarcoma is uncertain. In the absence of any formal validation of optimal timing and method of surveillance, guidance is provided by oncology societies' recommendations. FU is designed to detect either local recurrence or metastatic disease at a time when early treatment is still possible and might be effective. METHODS: We performed a retrospective analysis of 101 patients with high-grade extremity osteosarcoma in a single centre. Chest x-ray (CXR) was used as routine surveillance method; however patients with initial lung metastases or previous suspicious findings had computed tomography (CT) scans. RESULTS: With a median FU time of 30.7 months 34 patients relapsed. Relapse-free survival after 5 years was 61% (CI 52%; 73%), late relapses occurred in only two patients between 2 and 5 years of FU. Twenty-five of the 34 relapses were detected at routine FU appointments. All 8 local recurrences were noted clinically. Twenty-two patients had metastases confined to the lungs, either detected on CXR or CT. Thirty-two percent of patients with lung metastases only were salvaged successfully. CONCLUSIONS: Routine FU in high-grade osteosarcoma results in clinical detection of local relapse, and detection of lung metastases by CXR at a time when metastatectomy is possible. The optimal time interval for FU appointments is not known, however we recommend more frequent surveillance visits during the two years after treatment. We hypothesize that routine CT scans are not required and propose CXR for detection of lung metastases.

Development and validation of the BRIGHTLIGHT Survey, a patient-reported experience measure for young people with cancer.

BACKGROUND: Patient experience is increasingly used as an indicator of high quality care in addition to more traditional clinical end-points. Surveys are generally accepted as appropriate methodology to capture patient experience. No validated patient experience surveys exist specifically for adolescents and young adults (AYA) aged 13-24 years at diagnosis with cancer. This paper describes early work undertaken to develop and validate a descriptive patient experience survey for AYA with cancer that encompasses both their cancer experience and age-related issues. We aimed to develop, with young people, an experience survey meaningful and relevant to AYA to be used in a longitudinal cohort study (BRIGHTLIGHT), ensuring high levels of acceptability to maximise study retention. METHODS: A three-stage approach was employed: Stage 1 involved developing a conceptual framework, conducting literature/Internet searches and establishing content validity of the survey; Stage 2 confirmed the acceptability of methods of administration and consisted of four focus groups involving 11 young people (14-25 years), three parents and two siblings; and Stage 3 established survey comprehension through telephone-administered cognitive interviews with a convenience sample of 23 young people aged 14-24 years. RESULT: Stage 1: Two-hundred and thirty eight questions were developed from qualitative reports of young people's cancer and treatment-related experience. Stage 2: The focus groups identified three core themes: (i) issues directly affecting young people, e.g. impact of treatment-related fatigue on ability to complete survey; (ii) issues relevant to the actual survey, e.g. ability to answer questions anonymously; (iii) administration issues, e.g. confusing format in some supporting documents. Stage 3: Cognitive interviews indicated high levels of comprehension requiring minor survey amendments. CONCLUSION: Collaborating with young people with cancer has enabled a survey of to be developed that is both meaningful to young people but also examines patient experience and outcomes associated with specialist cancer care. Engagement of young people throughout the survey development has ensured the content appropriately reflects their experience and is easily understood. The BRIGHTLIGHT survey was developed for a specific research project but has the potential to be used as a TYA cancer survey to assess patient experience and the care they receive.

The Impact of Specialist Care on Teenage and Young Adult Patient-Reported Outcomes in England: A BRIGHTLIGHT Study.

Purpose: In England, health care policy promotes specialized age-appropriate cancer services for teenagers and young adults (TYA), for those aged 13-24 years at diagnosis. Specialist Principal Treatment Centers (PTCs) provide enhanced age-specific care for TYA, although many still receive all or some of their care in adult or children's cancer services. Our aim was to determine the patient-reported outcomes associated with TYA-PTC based care. Methods: We conducted a multicenter cohort study, recruiting 1114 TYA aged 13-24 years at diagnosis. Data collection involved a bespoke survey at 6,12,18, 24, and 36 months after diagnosis. Confounder adjusted analyses of perceived social support, illness perception, anxiety and depression, and health status, compared patients receiving NO-TYA-PTC care with those receiving ALL-TYA-PTC and SOME-TYA-PTC care. Results: Eight hundred and thirty completed the first survey. There was no difference in perceived social support, anxiety, or depression between the three categories of care. Significantly higher illness perception was observed in the ALL-TYA-PTC and SOME-TYA-PTC group compared to the NO-TYA-PTC group, (adjusted difference in mean (ADM) score on Brief Illness Perception scale 2.28 (95% confidence intervals [CI] 0.48-4.09) and 2.93 [1.27-4.59], respectively, p = 0.002). Similarly, health status was significantly better in the NO-TYA-PTC (ALL-TYA-PTC: ADM -0.011 [95%CI -0.046 to 0.024] and SOME-TYA-PTC: -0.054 [-0.086 to -0.023]; p = 0.006). Conclusion: The reason for the difference in perceived health status is unclear. TYA who accessed a TYA-PTC (all or some care) had higher perceived illness. This may reflect greater education and promotion of self-care by health care professionals in TYA units.

The Sarcoma Assessment Measure (SAM): Preliminary Psychometric Validation of a Novel Patient-Reported Outcome Measure.

The Sarcoma Assessment Measure (SAM) was developed as a sarcoma-specific patient-reported outcome measure to be used in clinical practice. We have reported in detail how SAM has been developed in collaboration with patients and healthcare professionals. The aim of this paper is to report the preliminary validation of SAM. The 22-item SAM was administered alongside a validated quality of life questionnaire and measure of activities of daily living. Linear modelling was used to build a measure, which had predictive validity in comparison to more established outcome measures. Of the 762 patients who participated in the study, 44.1% identified as male, and participant age ranged from 13 to 82 years. Clinically, participants presented with a range of soft tissue (82.2%) and bone (21.8%) sarcomas. Our preliminary analysis indicates that SAM accounts for 35% of the global quality of life scale and 18% of the Toronto Extremity Salvage Scale (TESS); so psychometrically, it overlaps with quality of life and activities of daily living, but also measures distinct concerns. This demonstrates that this measure picks up issues that are important to patients with sarcoma that are not reflected in other measures. We have established the preliminary validity of SAM and believe it has utility as a patient-reported outcome measure both as a research tool and for assessing the impact of symptoms and dysfunction related to sarcoma as part of clinical care. Further validation using a larger and more clinically diverse sample is now needed.

Young people's opinions of cancer care in England: the BRIGHTLIGHT cohort.

OBJECTIVES: The BRIGHTLIGHT cohort study was the national evaluation of cancer services for teenager and young adults (TYA). This was analysis of free-text survey data to better understand their experiences of cancer care. DESIGN: Cohort study SETTING: National Health Service hospitals delivering cancer care in England PARTICIPANTS: 830 young people newly diagnosed with cancer. INTERVENTIONS: Exposure to specialist care in the first 6 months after diagnosis defined as care in a TYA Principal Treatment Centre (PTC). This was categorised as follows: all care in a TYA-PTC (ALL-TYA-PTC), no care in a TYA-PTC (NO-TYA-PTC) so care delivered in a children/adult unit only and some care in a TYA-PTC with additional care in a children's/adult unit (SOME-TYA-PTC). PRIMARY OUTCOME: Data were collected through the BRIGHTLIGHT survey included free-text questions which asked patients 'what was the best aspects of their experiences of care' and 'what aspects could be improved'. These comments were analysed using content analysis. Themes were compared between categories of care, then ranked in order of frequency, ranging from the most endorsed to the least. RESULTS: Overall, young people were most positive about their healthcare team, while the area highlighted for improvement was diagnostic experience. Differences between the three groups suggested those who had some or all treatment in a TYA-PTC valued the place of care. Regardless of where TYA were treated their healthcare teams were favourably viewed. Age appropriate place of care was highlighted to be of value for those in PTCs. CONCLUSIONS: These data show the value young people placed on the care they received in TYA specific wards. Young people who accessed some or all of their care in a TYA-PTC highly endorsed their place of care as one of the best elements of their care, and it is further emphasised by those who had shared care who experienced difficulty with lack of age-appropriate care when treated outside the TYA-PTC.

Patients' Experiences of a Sarcoma Diagnosis: A Process Mapping Exercise of Diagnostic Pathways.

Patients with sarcoma often report prolonged time to diagnosis, which is attributed to the rarity of sarcoma and the low awareness of pre-diagnostic signs and symptoms. AIMS: To describe patients' experiences of pre-diagnostic signs/symptoms and pathways to diagnosis, including where help was sought, and the processes involved. METHODS: Mixed methods involving quantitative, qualitative and inductive thematic analyses using novel process mapping of patient journey data, as reported by the patients. We examined the time from symptom onset to first professional presentation (patient interval, PI), first consultation to diagnostic biopsy, first consultation to diagnosis (diagnostic interval) and first presentation to diagnosis (total interval). RESULTS: A total of 87 interviews were conducted over 5 months in 2017. Of these, 78 (40 males/38 females) were included. The sarcoma subtypes were bone (n = 21), soft tissue (n = 41), head and neck (n = 9) and gastro-intestinal (GIST; n = 7). Age at diagnosis was 13-24 (n = 7), 25-39 (n = 23), 40-64 (n = 34) and 65+ (n = 14) years. The median PI was 13 days (1-4971) and similar between sarcoma subtypes, with the exception of GIST (mPI = 2 days, (1-60). The longest mPI (31 days, range 4-762) was for those aged 13-24 years. The median diagnostic interval was 87.5 (range 0-5474 days). A total of 21 patients were misdiagnosed prior to diagnosis and symptoms were commonly attributed to lifestyle factors. CONCLUSIONS: Prolonged times to diagnosis were experienced by the majority of patients in our sample. Further research into the evolution of pre-diagnostic sarcoma symptoms is required to inform awareness interventions.

Germline genetic polymorphisms may influence chemotherapy response and disease outcome in osteosarcoma: a pilot study.

BACKGROUND: Osteosarcoma is the most common malignant bone tumor in children and young people. Efficacy of multiagent MAP (methotrexate, doxorubicin [Adriamycin], cisplatin) chemotherapy may be influenced by multiple cellular pathways. This pilot study aimed to investigate the association of 36 candidate genetic polymorphisms in MAP pathway genes with histological response, survival, and grade 3-4 chemotherapy toxicity in osteosarcoma. METHODS: Blood samples were obtained from 60 patients who had completed MAP chemotherapy. All patients were manually genotyped for 5 polymorphisms. The remaining 31 polymorphisms were genotyped in 50 patients using the Illumina 610-Quad microarray. Associations between candidate polymorphisms and histological response, progression-free survival, and toxicity were estimated using Pearson chi-square and Fisher exact tests, the Kaplan-Meier method, the log-rank test, and the Cox proportional hazards model. RESULTS: Poor histological response was increased in variants of ABCC2 c.24C>T (P = .011) and GSTP1 c.313A>G p.Ile(105)Val (P = .009), whereas MTHFD1 c.1958G>A p.Arg(653)Gln was protective (P = .03). Methotrexate toxicity was increased in variants of MTHFR c.1298A>C p.Glu(429)Ala (P = .038), ABCB1 c.3435T>C Ile(145)Ile (P = .027), and ABCC2 c.3563T>A p.Val(1188)Glu (P = .028). Variants of GSTP1 c.313A>G p.Ile(105)Val were at increased risk of myelosuppression (P = .024) and cardiac damage (P = .008). CONCLUSIONS: This pilot study represents the most comprehensive study to date examining the role of genetic polymorphisms in osteosarcoma. Although small and retrospective, it shows that several polymorphisms appear to significantly influence toxicity and clinical outcome. These deserve prospective validation in the hope of optimizing treatment for resistant disease and reducing the late effects burden.

A Qualitative Study of the Factors Influencing Patients' Experience of Soft Tissue Sarcoma in the United Kingdom.

BACKGROUND: Treatment of soft tissue sarcoma frequently involves extensive surgery, loss of mobility, and complex rehabilitation programs. Poorer patient-reported outcomes are reported in comparison to those from patients with other cancer types. Understanding patient experience is therefore important to support patients and improve care. OBJECTIVE: The aim of this study was an in-depth exploration of patients' experience of being diagnosed with soft tissue sarcoma. METHODS: Semistructured interviews and focus groups were conducted with 68 patients with soft tissue sarcoma (59% female; aged 23-82 years). These were analyzed using adapted framework analysis. RESULTS: Two overarching themes explained the factors influencing patients' experiences: individual and social factors to manage the impact of soft tissue sarcoma; and context and processes of care. Access to professionals with sarcoma expertise and services in specialist hospitals had an impact on patients' well-being. Lack of access to specialist services and coordinated care were associated with worse experiences. These were influenced by age and support from family/friends/other patients and were crucial in patients' adaptation to living with and beyond a sarcoma diagnosis. CONCLUSION: We describe factors that both negatively and positively influenced the experience of patients with soft tissue sarcoma. Access to specialist soft tissue sarcoma and rehabilitation services and support tailored to patients' age and disease trajectory are needed to improve these experiences. IMPLICATION FOR PRACTICE: Nurses are important for helping patients manage the long-term effects and directing them to supportive care services. Rehabilitation services need to be available and easily accessible.

The BRIGHTLIGHT National Survey of the Impact of Specialist Teenage and Young Adult Cancer Care on Caregivers' Information and Support Needs.

BACKGROUND: Teenage and young adult cancer services in England are centralized in 13 principal treatment centers (TYA-PTC). These "specialist services" are designed to support caregivers as well as young people. OBJECTIVES: To evaluate whether caregivers of young people with cancer had fewer unmet information and support needs if they had all/some care in a TYA-PTC. METHODS: Participants in a cohort study of young people with cancer nominated their main carer to complete the BRIGHTLIGHT Carer Questionnaire, completed 6 months after diagnosis. Comparisons were made according to where young people's care was delivered: all, some, or no care in a TYA-PTC. Principal components analysis reduced the questionnaire to 5 dimensions, which were used as dependent variables in subsequent regression analysis. RESULTS: Four hundred seventy-six responses of 514 returned questionnaires (92%) were included in the analysis. The majority of caregivers were white, middle-aged, married/cohabiting mothers. Adjusted analysis indicated caregivers who had all/some care in a TYA-PTC had more satisfaction with support and also with services specifically provided for carers. Those who had some TYA-PTC care had greater satisfaction with information but less opportunity to be involved in decisions. CONCLUSIONS: Caregivers of young people who had no TYA-PTC care have the most unmet information and support needs. IMPLICATIONS FOR PRACTICE: Nurses outside of the TYA-PTC need to be supported by the TYA-PTC in providing information/support for caregivers. When a young person is receiving care in multiple hospitals, nurses need to optimize opportunities for caregivers to be involved in decision making.

BRIGHTLIGHT researchers as 'dramaturgs': creating There is a Light from complex research data.

BACKGROUND: BRIGHTLIGHT is a national evaluation of cancer services for young people aged 13-24 years in England. It is a mixed methods study with six interlinked studies aiming to answer the question: do specialist cancer services for teenagers and young adults add value? http://www.brightlightstudy.com/. Young people have been integral to study development and management, working as co-researchers, consultants and collaborators throughout. We aimed to share results in a way that was meaningful to young people, the public, and multidisciplinary professionals. This paper reports the development of 'There is a Light: BRIGHTLIGHT', a theatrical interpretation of study results by young people, and offers insight into the impact on the cast, researchers and audiences. METHODS: The BRIGHTLIGHT team collaborated with Contact Young Company, a youth theatre group in Manchester. Twenty members of Contact Young Company and four young people with cancer worked together over an eight-week period during which BRIGHTLIGHT results were shared along with explanations of cancer, healthcare policy and models of care in interactive workshops. Through their interpretation, the cast developed the script for the performance. The impact of the process and performance on the cast was evaluated through video diaries. The research team completed reflective diaries and audiences completed a survey. RESULTS: 'There is a Light' contained five acts and lasted just over an hour. It played 11 performances in six cities in the United Kingdom, to approximately 1377 people. After nine performances, a 30-min talk-back between members of the cast, creative team, an expert healthcare professional, and the audience was conducted, which was attended by at least half the audience. Analysis of cast diaries identified six themes: initial anxieties; personal development; connections; cancer in young people; personal impact; interacting with professionals. The cast developed strong trusting relationships with the team. Professionals stated they felt part of the process rather than sitting on the periphery sharing results. Both professional and lay audiences described the performance as meaningful and understandable. Feedback was particularly positive from those who had experienced cancer themselves. CONCLUSIONS: Using theatre to present research enabled BRIGHTLIGHT results to be accessible to a larger, more diverse audience.

Description of the BRIGHTLIGHT cohort: the evaluation of teenage and young adult cancer services in England.

OBJECTIVE: International recognition of the unique needs of young people with cancer is growing. Many countries have developed specialist age-appropriate cancer services believing them to be of value. In England, 13 specialist principal treatment centres (PTCs) deliver cancer care to young people. Despite this expansion of specialist care, systematic investigation of associated outcomes and costs has, to date, been lacking. The aim of this paper is to describe recruitment and baseline characteristics of the BRIGHTLIGHT cohort and the development of the bespoke measures of levels of care and disease severity, which will inform the evaluation of cancer services in England. DESIGN: Prospective, longitudinal, observational study. SETTING: Ninety-seven National Health Service hospitals in England. PARTICIPANTS: A total of 1114 participants were recruited and diagnosed between July 2012 and December 2014: 55% (n=618) were men, mean age was 20.1 years (SD=3.3), most (86%) were white and most common diagnoses were lymphoma (31%), germ cell tumour (19%) and leukaemia (13%). RESULTS: At diagnosis, median quality of life score was significantly lower than a published control threshold (69.7 points); 40% had borderline to severe anxiety, and 21% had borderline to severe depression. There was minimal variation in other patient-reported outcomes according to age, diagnosis or severity of illness. Survival was lower in the cohort than for young people diagnosed during the same period who were not recruited (cumulative survival probability 4 years after diagnosis: 88% vs 92%). CONCLUSIONS: Data collection was completed in March 2018. Longitudinal comparisons will determine outcomes and costs associated with access/exposure to PTCs. Findings will inform international intervention and policy initiatives to improve outcomes for young people with cancer.

A Critical Review of the Impact of Sarcoma on Psychosocial Wellbeing.

BACKGROUND: Previous reviews of outcomes in specific sarcoma populations suggest patients have poor quality of life. In most of these reviews, there is a predominant focus on physical function rather than psychosocial outcome. The aim of this review was to describe the psychosocial impact of diagnosis and treatment on patients with all types of sarcoma. METHODS: Searches were conducted through six electronic databases for publications of any study design using a validated patient-reported outcome measure reporting the psychosocial impact in this population. RESULTS: Eighty-two studies fulfilled the inclusion criteria. Most (65%) were assessed of being of reasonable quality. The most common aspect of psychosocial wellbeing measured was quality of life (80%). Due to the heterogeneity of methods, outcomes, and populations, it was not possible to make definitive conclusions. It seems there is an improvement in the physical aspects of quality of life over time but not in psychosocial function or mental health. There was no change in mental health scores, but patients reported an improvement in adjusting to normal life. There are no differences according to the type of surgery patients receive, and psychosocial outcomes tend to be poorer than the general population. There is no consistency in identifying the factors that predict/influence psychosocial wellbeing. CONCLUSION: The published literature does not provide a clear understanding of the impact of sarcoma diagnosis and treatment on psychosocial wellbeing. Instead, the review demonstrates a need for well-designed studies in this area and a more consistent approach to the measurement of patient-reported outcomes, which include psychosocial domains. Recommendations for future research have been proposed.

Qualitative study exploring patients experiences of being diagnosed and living with primary bone cancer in the UK.

OBJECTIVE: The aim of this study is to explore the experiences of patients with primary bone cancer. DESIGN: Qualitative study design using semistructured interviews and focus groups. SETTING: Hospitals across the UK and recruitment through UK sarcoma charities and support groups. METHODS: Semistructured telephone/face-to-face interviews and focus groups with a purposive sample of 26 participants. Data were analysed using Framework Analysis. PARTICIPANTS: Patients (n=26) with primary bone cancer aged 13-77 years. The majority were male (69%), white (85%); diagnosed within 4 years (54%); and had lower limb sarcoma (65%). Ten participants had undergone an upper/lower limb amputation (39%). RESULTS: The health-related quality-of-life domains of physical, emotional and social well-being and healthcare professionals' role were the overarching themes of analysis. The physical domain anchored patient experiences. The intensity and length of treatment, the severity of side-effects, the level of disability after surgery and the uncertainty of their prognosis had an impact on patient's self-image, confidence, mood and identity, and caused disruption to various aspects of the patients' social life, including their relationships (emotional and sexual) and participation in work/school and leisure activities. Adaptation was influenced by the way patients dealt with stress and adversity, with some finding a new outlook in life, and others struggling with finding their 'new normal'. Family and friends were the main source of support. Healthcare professional's expertise and support was critical. Rehabilitation services had a considerable role in patient's physical and emotional well-being, but inequitable access to these services was apparent. CONCLUSIONS: This study described the impact of primary bone cancer on patients' well-being and adjustment over time with the identification of influencing factors of better/worse experiences. It showed that impact was felt after end of treatment and affected patients at different life stages. Holistic models of survivorship care are needed.

Research priorities for young people with cancer: a UK priority setting partnership with the James Lind Alliance.

OBJECTIVES: To conduct a UK-wide survey of young people who have experienced cancer, carers and professionals, to identify and prioritise research questions to inform decisions of research funders and support the case for research with this unique cancer population. DESIGN: James Lind Alliance Priority Setting Partnership. SETTING: UK health service and community. METHODS: A steering group oversaw the initiative and partner organisations were recruited. Unanswered questions were collected in an online survey. Evidence searching verified uncertainties. An interim survey was used to rank questions prior to a final prioritisation workshop. PARTICIPANTS: Young people aged 13-24 years with a current or previous cancer diagnosis, their families, friends, partners and professionals who work with this population. RESULTS: Two hundred and ninety-two respondents submitted 855 potential questions. Following a refining process and removal of 'out of scope' questions, 208 unique questions remained. Systematic evidence checking identified seven answered questions and 16 were the subject of ongoing studies. The interim survey was completed by 174 participants. The top 30 questions were prioritised at a workshop attended by 25 young people, parents and multidisciplinary professionals. The top three priorities are: (1) What psychological support package improves psychological well-being, social functioning and mental health during and after treatment? (2) What interventions, including self-care, can reduce or reverse adverse short-term and long-term effects of cancer treatment? (3) What are the best strategies to improve access to clinical trials? The remaining questions reflect the complete cancer pathway: new therapies, life after cancer, support, education/employment, relapse and end-of-life care. CONCLUSIONS: We have identified shared research priorities for young people with cancer using a rigorous, person-centred approach involving stakeholders typically not involved in setting the research agenda. The breadth of priorities suggest future research should focus on holistic and psychosocial care delivery as well as traditional drug/biology research.

Emerging chemotherapeutic strategies and the role of treatment stratification in Ewing sarcoma.

The Ewing sarcoma family of tumors (ESFT) is one of the most common groups of malignancies arising in children, adolescents, and young adults up to approximately 25 years of age. It comprises Ewing sarcoma arising from bone and extraosseous Ewing sarcoma arising from soft tissues (which includes peripheral neuroectodermal tumors and Askin tumor arising from the chest wall). Ewing sarcoma is treated successfully in many cases by a combination of chemotherapy, surgery, and radiotherapy. A number of prognostic factors have been identified that can be used to stratify patients according to the risk of relapse, allowing optimization of treatment. These can be categorized as tumor-related factors (presence of metastases, tumor site, volume, lactic dehydrogenase level, chromosomal translocation type, presence of fusion transcripts in blood and bone marrow), treatment-related factors (local therapy, histologic response to chemotherapy, radiologic response to chemotherapy, chemotherapy regimen), and patient-related factors (gender, age). Newer chemotherapeutic agents are currently being investigated, and there is now increasing interest in the identification of molecular targets in ESFT that could be exploited therapeutically, which include the mammalian target of rapamycin (mTOR) and insulin growth factor-1 (IGF-1) receptor pathways.

Osteosarcoma, Chondrosarcoma, and Chordoma.

Osteosarcoma (OS), chondrosarcoma, and chordoma are characterized by multiple challenges to the investigator, clinician, and patient. One consequence of their rarity among sarcomas, as well as their biologic and clinical heterogeneity, is that management guidelines are inadequate to inform the range of individual patient-treatment decisions from diagnosis, approaches to surgery, chemotherapy, radiotherapy, treatment of recurrence, palliative care, and quality of survivorship. Of high-grade sarcomas, OSs are among the most curable, with more than two-thirds of patients with localized disease likely to achieve long-term survival. Neoadjuvant chemotherapy comprising cisplatin, doxorubicin, and methotrexate with intercalated surgery is the standard of care for resectable OS in those younger than 40 years. Outcomes for OS presenting with unresectable metastases or recurrent disease, or in those older than 40 years are generally poor. Overall results have improved little for all patients with OS, and new treatments are needed. Surgical resection remains the cornerstone of management for chondrosarcoma and chordoma. However, the application of new biologic insights to therapeutic development indicates that improved treatments may soon be routine for patients with chondrosarcoma and chordoma for whom surgery alone is inadequate. For all these uncommon diseases, patients should be offered specialist expert care delivered by experienced multidisciplinary teams in high-volume centers.