Jeremy Whelan

Developing a conceptual model of teenage and young adult experiences of cancer through meta-synthesis.

OBJECTIVESnTo systematically identify and analyse published research exploring teenage and young adult experience of cancer to inform the development of a patient-reported outcome survey intended to explore if a correlation exists between specialist cancer care and quality of life for young people with cancer.nnnDESIGNnSystematic review and meta-synthesis.nnnDATA SOURCESnMedline, CINAHL Plus and PsycInfo were searched for literature published between 1987 and 2011.nnnREVIEW METHODSnSearch terms included those for: population (e.g. teen, young adult); intervention (e.g. cancer); outcome (e.g. experience); and study type (e.g. qualitative).nnnINCLUSION CRITERIAnadolescents and young adults were both represented; diagnosis of cancer; published in English; and used qualitative methods to report an aspect of the cancer experience. Studies were excluded if they were reporting: palliative care experience; secondary data; or proxy views, i.e. parent or health professional perspective. Methodological quality was assessed using Cesario criteria and meta-synthesis involved deconstruction and decontextualising findings to identify common themes.nnnRESULTSnThree hundred and fifteen studies were identified, 17 fulfilled the inclusion criteria. Of these, most (59%), were assessed as being high quality, none were rated poor. Nine common themes were identified: psychosocial function, importance of peers, experience of healthcare, importance of support, impact of symptoms, striving for normality, impact of diagnosis, positive experiences, and financial consequences.nnnCONCLUSIONSnThe conceptual model developed from the meta-synthesis depicts the mediators and consequences of cancer care that impact on young peoples quality of life after a cancer diagnosis. The model highlights areas that require further exploration.

Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial

Summary Background For many years, first-line treatment for locally advanced or metastatic soft-tissue sarcoma has been doxorubicin. This study compared gemcitabine and docetaxel versus doxorubicin as first-line treatment for advanced or metastatic soft-tissue sarcoma. Methods The GeDDiS trial was a randomised controlled phase 3 trial done in 24 UK hospitals and one Swiss Group for Clinical Cancer Research (SAKK) hospital. Eligible patients had histologically confirmed locally advanced or metastatic soft-tissue sarcoma of Trojani grade 2 or 3, disease progression before enrolment, and no previous chemotherapy for sarcoma or previous doxorubicin for any cancer. Patients were randomly assigned 1:1 to receive six cycles of intravenous doxorubicin 75 mg/m2 on day 1 every 3 weeks, or intravenous gemcitabine 675 mg/m2 on days 1 and 8 and intravenous docetaxel 75 mg/m2 on day 8 every 3 weeks. Treatment was assigned using a minimisation algorithm incorporating a random element. Randomisation was stratified by age (≤18 years vs >18 years) and histological subtype. The primary endpoint was the proportion of patients alive and progression free at 24 weeks in the intention-to-treat population. Adherence to treatment and toxicity were analysed in the safety population, consisting of all patients who received at least one dose of their randomised treatment. The trial was registered with the European Clinical Trials (EudraCT) database (no 2009–014907–29) and with the International Standard Randomised Controlled Trial registry (ISRCTN07742377), and is now closed to patient entry. Findings Between Dec 3, 2010, and Jan 20, 2014, 257 patients were enrolled and randomly assigned to the two treatment groups (129 to doxorubicin and 128 to gemcitabine and docetaxel). Median follow-up was 22 months (IQR 15·7–29·3). The proportion of patients alive and progression free at 24 weeks did not differ between those who received doxorubicin versus those who received gemcitabine and docetaxel (46·3% [95% CI 37·5–54·6] vs 46·4% [37·5–54·8]); median progression-free survival (23·3 weeks [95% CI 19·6–30·4] vs 23·7 weeks [18·1–20·0]; hazard ratio [HR] for progression-free survival 1·28, 95% CI 0·99–1·65, p=0·06). The most common grade 3 and 4 adverse events were neutropenia (32 [25%] of 128 patients who received doxorubicin and 25 [20%] of 126 patients who received gemcitabine and docetaxel), febrile neutropenia (26 [20%] and 15 [12%]), fatigue (eight [6%] and 17 [14%]), oral mucositis (18 [14%] and two [2%]), and pain (ten [8%] and 13 [10%]). The three most common serious adverse events, representing 111 (39%) of all 285 serious adverse events recorded, were febrile neutropenia (27 [17%] of 155 serious adverse events in patients who received doxorubicin and 15 [12%] of 130 serious adverse events in patients who received gemcitabine and docetaxel, fever (18 [12%] and 19 [15%]), and neutropenia (22 [14%] and ten [8%]). 154 (60%) of 257 patients died in the intention-to-treat population: 74 (57%) of 129 patients in the doxorubicin group and 80 (63%) of 128 in the gemcitabine and docetaxel group. No deaths were related to the treatment, but two deaths were due to a combination of disease progression and treatment. Interpretation Doxorubicin should remain the standard first-line treatment for most patients with advanced soft-tissue sarcoma. These results provide evidence for clinicians to consider with their patients when selecting first-line treatment for locally advanced or metastatic soft-tissue sarcoma. Funding Cancer Research UK, Sarcoma UK, and Clinical Trial Unit Kantonsspital St Gallen.

Can postoperative radiotherapy be omitted in localised standard-risk Ewing sarcoma? An observational study of the Euro-E.W.I.N.G group

BACKGROUNDnThe role of postoperative radiotherapy (PORT) in Ewing sarcoma (ES) is unclear. We assessed the impact of PORTxa0on local control in patients with localised ES and good histological response to chemotherapy (<10% cells).nnnPATIENTS AND METHODSnAll randomised patients in the EE99-R1 trial (comparing two consolidation chemotherapy regimens) undergoing surgery after induction chemotherapy were included. Local relapse (LR) cumulative incidence was estimated using a competing risk approach. Impact of PORT was assessed in multivariable models, adjusted for country, age, tumour site and volume, quality of resection and histological response. We also evaluated the heterogeneity of PORT effect by patient and tumour characteristics.nnnRESULTSnOne hundred forty-two (24%) of the 599 patients included from 1999 to 2009 received PORT (median dose: 45 Grays). With median follow-up of 6.2 years, 67 patients had an LR (with concomitant metastases in 28), leading to an 8-year LR-incidencexa0=xa011.9% (standard error [se]xa0=xa01.4%). Overall survival (OS)xa0=xa021% (sexa0=xa05%) 3 years after LR (31% in isolated LR). Controlling for possible confounders, we observed a statistically significant reduction of LR in patients treated by surgeryxa0+xa0PORT compared to surgery alone (subdistribution-hazard ratioxa0=xa00.43, 95% confidence interval, 0.21-0.88, pxa0=xa00.02). The benefit of PORT was particularly marked for tumours larger than 200xa0ml at diagnosis and 100% necrosis. We observed a non-significant trend for benefit associated with PORT for disease-free, event-free and OS.nnnCONCLUSIONnRadiotherapy appears to improve local control. We now recommend PORT in case of incomplete removal of the tissues involved by the pre-chemotherapy tumour volume. Further studies are required to assess the balance between benefit and risks.

A scoping exercise of favourable characteristics of professionals working in teenage and young adult cancer care: 'thinking outside of the box'

A scoping exercise to define the preferred competencies of professionals involved in teenage and young adult (TYA) cancer care. Data were generated during two workshops with health professionals. In groups, they ranked skills, knowledge and attitudes, previously identified through a literature search, onto a diamond template. Data were also used from an education day with TYA professionals, who generated lists of key skills, knowledge and attitudes. Individually, professionals then selected the top five areas of competence to care for young people with cancer. The workshops generated three diamonds, which exhibited agreement of 13 principle skills, knowledge and attitudes. The top two being: expertise in treating paediatric and adult cancers and understanding cancer. The data from the education day suggested communication, technical knowledge and teamwork as being core role features for professionals who care for young people with cancer. Integration of both datasets; one derived inductively, the other deductively provides a comprehensive outline of core skills health professionals require to be proficient in young peoples cancer care. These results will form the basis of future discussion around workforce strategies and inform a Delphi survey.GIBSON F., FERN L., WHELAN J., PEARCE S., LEWIS I.J., HOBIN D. & TAYLOR R.M. (2012) European Journal of Cancer Care21, 330–339 n n n nA scoping exercise of favourable characteristics of professionals working in teenage and young adult cancer care: ‘thinking outside of the box’ n n n nA scoping exercise to define the preferred competencies of professionals involved in teenage and young adult (TYA) cancer care. Data were generated during two workshops with health professionals. In groups, they ranked skills, knowledge and attitudes, previously identified through a literature search, onto a diamond template. Data were also used from an education day with TYA professionals, who generated lists of key skills, knowledge and attitudes. Individually, professionals then selected the top five areas of competence to care for young people with cancer. The workshops generated three diamonds, which exhibited agreement of 13 principle skills, knowledge and attitudes. The top two being: ‘expertise in treating paediatric and adult cancers’ and ‘understanding cancer’. The data from the education day suggested communication, technical knowledge and teamwork as being core role features for professionals who care for young people with cancer. Integration of both datasets; one derived inductively, the other deductively provides a comprehensive outline of core skills health professionals require to be proficient in young peoples cancer care. These results will form the basis of future discussion around workforce strategies and inform a Delphi survey.

A participatory study of teenagers and young adults views on access and participation in cancer research.

PURPOSEnThe purpose of this study was to elicit young peoples views on access and participation in cancer research.nnnMETHODSnEight young people aged 18-25 years with a previous cancer diagnosis aged 15-24 participated in a one day workshop utilising participatory methodology. The workshop consisted of four exercises: role play/scene setting; focus group examining thoughts and opinions of research access and participation; individual reflection on access to different types of research; and creative interpretation of the workshop. Further consultation with 222 young people with cancer was conducted using an electronic survey.nnnRESULTSnThree themes emerged: • Patient choice: Young people thought it was their right to know all options about available research. Without knowledge of all available studies they would be unable to make an informed choice about participation. • Role of healthcare professionals as facilitators/barriers: Young people suggested non-clinical healthcare professionals such as social workers and youth support coordinators may be more suited to approaching young people about participation in psychosocial and health services research. • Value of the research: The what, when and how information was delivered was key in relaying the value of the study and assisting young people in their decision to participate. Further consultation showed approximately 70% wanted to find out about all available research. However, one third trusted healthcare professionals to decide which research studies to inform them of.nnnCONCLUSIONnEffective ways to support healthcare professionals approaching vulnerable populations about research are needed to ensure young people are empowered to make informed choices about research participation.

The perceptions of teenagers, young adults and professionals in the participation of bone cancer clinical trials

The reasons why teenagers and young adults (TYA) with cancer do, or do not, participate in clinical trials is not wholly understood. We explored the perceptions and experiences of young people with bone cancer, and health professionals involved in their care, with regard to participation in two clinical trials. We conducted semi-structured interviews using narrative inquiry with 21 young people aged 15-24xa0years and 18 health professionals. New understandings emerged about perceptions of, and factors that influence participation in, clinical trials. These include perceptions about the importance and design of the clinical trial, communicating with young people in an age-specific manner, using language young people are comfortable with, support from family, peers and specialists in teenage and young adult cancer care. We conclude that addressing these factors may increase acceptability of clinical trials and the trial design for TYA with cancer and ultimately improve their participation. Qualitative research has an important role in making explicit the perceptions and practices that ensure trials are patient-centred, appropriate and communicated effectively to TYA. Translating knowledge gained into routine practice, will go some way in ensuring that the disparities affecting this population are more fully understood.

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.

Direct access to potential research participants for a cohort study using a confidentiality waiver included in UK National Health Service legal statutes

Objectives To describe our experience of using a confidentiality waiver (Section 251) in the National Health Service (NHS) Act to identify and recruit potential research participants to a cohort study and consider its use in a wider research context. Design Methodological discussion. Setting NHS Trusts in England. Methods We established a research recruitment process with quality health (QH), administrators of the National Cancer Patient Experience Survey, after an amendment to a Section 251 approval (reference number ECC-8-05d-2011). NHS Trusts agreeing to implement the process were requested to send the details of 16–24-year-olds, identified by a relevant ICD-10 code indicating a cancer diagnosis within a specified time period to QH. QH sent study information and a consent-to-be-contacted form which allowed QH to send details to BRIGHTLIGHT, for BRIGHTLIGHT to contact the treating team confirming eligibility and for an interviewer from Ipsos MORI to contact them. Written consent was to be obtained at interview. Results The method was implemented in 98 trusts; 75 supplied patient details. QH sent information to 441 young people, of whom 64 (15%) responded. Of these, 23 had already consented to participate. Adverse events were reported by 6 (1%) invitees: 4 were distressed because they did not have cancer, their details being submitted to QH due to incorrect hospital coding, and 1 young person was distressed about their diagnosis and requested no further contact and 1 young person found out they had cancer from the invitation. Conclusions Application of Section 251 of the NHS Act (2006) to directly approach participants can facilitate recruitment to research projects where routinely collected NHS data are available to select eligible patients. The benefits of this method are that it requires fewer resources to recruit across multiple sites, and is quicker. Further information on the impact on bias and adverse event profile are required.

Respiratory mortality of childhood, adolescent and young adult cancer survivors

Background Exposure to radiation and/or chemotherapy during cancer treatment can compromise respiratory function. We investigated the risk of long-term respiratory mortality among 5-year cancer survivors diagnosed before age 40 years using the British Childhood Cancer Survivor Study (BCCSS) and Teenage and Young Adult Cancer Survivor Study (TYACSS). Methods The BCCSS comprises 34 489 cancer survivors diagnosed before 15 years from 1940 to 2006 in Great Britain. The TYACSS includes 200 945 cancer survivors diagnosed between 15 years and 39 years from 1971 to 2006 in England and Wales. Standardised mortality ratios and absolute excess risks were used. Findings Overall, 164 and 1079 respiratory deaths were observed in the BCCSS and TYACSS cohorts respectively, which was 6.8 (95%u2009CI 5.8 to 7.9) and 1.7 (95%u2009CI 1.6 to 1.8) times that expected, but the risks varied substantially by type of respiratory death. Greatest excess numbers of deaths were experienced after central nervous system (CNS) tumours in the BCCSS and after lung cancer, leukaemia, head and neck cancer and CNS tumours in the TYACSS. The excess number of respiratory deaths increased with increasing attained age, with seven (95%u2009CI 2.4 to 11.3) excess deaths observed among those aged 50+ years inu2009the BCCSS and three (95%u2009CI 1.4 to 4.2) excess deaths observed among those aged 60+ years inu2009the TYACSS. It was reassuring to see a decline in the excess number of respiratory deaths among those diagnosed more recently in both cohorts. Conclusions Prior to this study, there was almost nothing known about the risks of respiratory death after cancer diagnosed in young adulthood, and this study addresses this gap. These new findings will be useful for both survivors and those involved in their clinical management and follow-up.

Diagnostic timeliness in adolescents and young adults with cancer: a cross-sectional analysis of the BRIGHTLIGHT cohort

Summary Background Adolescents and young adults (AYAs) are thought to experience prolonged intervals to cancer diagnosis, but evidence quantifying this hypothesis and identifying high-risk patient subgroups is insufficient. We aimed to investigate diagnostic timeliness in a cohort of AYAs with incident cancers and to identify factors associated with variation in timeliness. Methods We did a cross-sectional analysis of the BRIGHTLIGHT cohort, which included AYAs aged 12–24 years recruited within an average of 6 months from new primary cancer diagnosis from 96 National Health Service hospitals across England between July 1, 2012, and April 30, 2015. Participants completed structured, face-to-face interviews to provide information on their diagnostic experience (eg, month and year of symptom onset, number of consultations before referral to specialist care); demographic information was extracted from case report forms and date of diagnosis and cancer type from the national cancer registry. We analysed these data to assess patient interval (time from symptom onset to first presentation to a general practitioner [GP] or emergency department), the number of prereferral GP consultations, and the symptom onset-to-diagnosis interval (time from symptom onset to diagnosis) by patient characteristic and cancer site, and examined associations using multivariable regression models. Findings Of 1114 participants recruited to the BRIGHTLIGHT cohort, 830 completed a face-to-face interview. Among participants with available information, 204 (27%) of 748 had a patient interval of more than a month and 242 (35%) of 701 consulting a general practitioner had three or more prereferral consultations. The median symptom onset-to-diagnosis interval was 62 days (IQR 29–153). Compared with male AYAs, female AYAs were more likely to have three or more consultations (adjusted odds ratio [OR] 1·6 [95% CI 1·1–2·3], p=0·0093) and longer median symptom onset-to-diagnosis intervals (adjusted median interval longer by 24 days [95% CI 11–37], p=0·0005). Patients with lymphoma or bone tumours (adjusted OR 1·2 [95% CI 0·6–2·1] compared with lymphoma) were most likely to have three or more consultations and those with melanoma least likely (0·2 [0·1–0·7] compared with lymphoma). The adjusted median symptom onset-to-diagnosis intervals were longest in AYAs with bone tumours (51 days [95% CI 29–73] longer than for lymphoma) and shortest in those with leukaemia (33 days [17–49] shorter than for lymphoma). Interpretation The findings provide a benchmark for diagnostic timeliness in young people with cancer and help to identify subgroups at higher risk of a prolonged diagnostic journey. Further research is needed to understand reasons for these findings and to prioritise and stratify early diagnosis initiatives for AYAs. Funding National Institute for Health Research, Teenage Cancer Trust, and Cancer Research UK.