The NCRI TYA & GCT Group identified their strategic priorities in August 2022 to address challenges faced in teenage and young adult and germ cell tumour research and to ultimately improve outcomes for patients with currently unmet needs.

NCRI TYA & GCT Group strategic priorities

TYA & GCT Group priorities

Identify the barriers resulting in a lack of diversity in patient and public involvement and engagement in developing TYA and GCT clinical trials and propose solutions to improve equality, diversity and inclusion.

This priority aims to establish the reasons behind a lack of diversity in clinical trials and provide solutions to increase participation of a cohort of patients with very specific needs within future studies. A working group will produce guidelines on the steps to take to improve inclusion of patients from a range of backgrounds into clinical trials from their inception.

Develop a platform study for newly diagnosed TYA cancer. 

Historically, factors identified that may contribute to poorer outcomes in TYA patients include delays in diagnosis or treatment, inappropriate treatments, lack of clinical trials or access to clinical trials, lack of TYA expertise and different biological characteristics of Adolescents and Young Adult (AYA) tumours. The new NHS England and NHS Improvement service specification for TYA cancer (expected to be published in the near future) will emphasise the importance of tumour banking, embedding genomic medicine in TYA services and clinical trial access in TYA patients.  An increasing understanding of the clinical relevance of molecular subtypes of common TYA cancers, molecular profiling and whole genome sequencing for all paediatric tumours, sarcomas and soon to be for all patients aged up to 24 years,  molecular profiling initiatives in the relapse setting such as the Strat Med Paeds study and the increasing availability of biomarker-driven basket studies for relapsed haematological malignancies and solid tumours provide a pressing imperative to ensure that all AYA patients are offered access to molecular profiling and relevant biomarker-driven clinical trials.  With appropriate consent, such data could also be linked to other relevant clinical datasets to build a more comprehensive picture of individual AYA cancer care and to better understand the interaction of tumour molecular profiling, place of care, clinical trial access with survival, late effects and patient reported outcomes in the AYA population.

Identify the challenges faced in TYA and GCT research and propose solutions. 

This priority aims to establish a joint consensus on the future of TYA and GCT research across the UK, with a focus on collaboration as opposed to competition, and produce and publish a position statement with proposed solutions to the challenges currently faced. Within the position statement, challenges such as the lack of integrated clinical-biological-psychosocial datasets for shared analysis and the lack of sharing of clinical trial data in GCT trials through global data commons will be addressed.

Improve outcomes for patients with early onset colorectal cancer. 

The aim of this priority is to evaluate epidemiological and clinico-pathological features of early onset colorectal carcinoma to inform development of preventative, screening and management strategies, and ultimately to improve outcomes. The NCRI TYA & GCT Group has put in place the collaborations that bring together the NHS Digital national cancer registry and SACT datasets to determine the UK epidemiology, delivered treatments and outcomes for people aged 15-39 years and compare them with those aged 40+years. We will now hold a workshop to expand this into biological and intervention questions, building upon UK tumour banks and existing clinical trials cohorts to determine their coverage of the range of specific biological targets and develop plans for future trials and result in a grant proposal.

Develop research questions relating to teenagers and young adults returning to education and the workplace after cancer.

The teenage and young adult cancer community took part in the James Lind Alliance (JLA) Priority Setting Partnership (PSP) process in 2019 to identify the most pressing needs in the field with a particular focus on hearing the voices of patients, carers and those affected by cancer. The aim of this priority is to hold a workshop to develop trials addressing the following JLA priorities:

  • What interventions are most effective in supporting young people who are experiencing fatigue/tiredness when returning to education or work?
  • What interventions are most effective in supporting young people when returning to education or work?
  • What methods of support from education/school for young people improve wellbeing, participation and mental health?
  • What interventions are most effective in supporting young people to maintain their education whilst on treatment?
  • How are career choices and prospects affected by a cancer diagnosis and are some groups more at risk of encountering issues than others?
  • What interventions can reduce the potential negative impact of a cancer diagnosis on a young person’s employment and career prospects?
  • How can schools and teachers better support young people with memory problems following cancer?
  • How are young people best supported to reintegrate with their peers when returning to school?
  • What is the educational trajectory of young people with cancer from 6 months pre diagnosis up to age 18?
  • What interventions can reduce the potential negative impact of a cancer diagnosis on a young person’s employment and career prospects?

Improve understanding of the genetics and genomics of treatment-resistant disease. 

We will build upon current basket trials of biologically targeted therapies and global collaborations to understand the genetics and genomics of treatment-resistant disease in TYA cancer. We will link clinical features, active biological pathways and access to novel targeted therapies. This will also build upon the ECMC current initiatives in TYA cancer. Precise outputs of this priority are dependent on ongoing trials but are likely to include a publication or position paper. One exemplar will be GCT, and input from the GCT Study Group will be integral in delivering this priority. There is an urgent need to understand at a molecular level what underpins drug-refractoriness/resistance such that different and more effective treatment strategies can be employed. This priority will require tumour (primary and metastases) banking and molecular characterisation studies. ctDNA studies could also be considered. This will proceed alongside exemplars in TYA-onset sarcomas, -brain tumours and -lymphomas, for example.

Identify immunology- and immunotherapy-related research questions that can be addressed using retrospective and prospective data.  

Immunology and immunotherapy are areas of cancer medicine that are rapidly moving without a current TYA angle, while there is clear evidence of variation in immunological profiles by age. We would like to link with the British Society of Immunology (BSI) and hold a workshop to discuss immunology, immunotherapy and age to identify the salient current questions that can be addressed using retrospective and prospective data.

Potential projects/key questions to consider in this workshop include:

  • Constitution and immune changes across age
  • Immunogenicity of biology of young onset cancers
  • Pharmacology of immune-oncology agents in young adults

Assess and improve end of life in teenagers and young adults with cancer.

The NCRI TYA & GCT Group has developed work in end-of -life care in the BRIGHTLIGHT programme. We wish to build a cross-speciality group with the Living With and Beyond Cancer (LWBC) and palliative care communities, our networks and the age-specific expertise and clinical linkages from within the TYA & GCT Group to further develop work in this area. Questions to consider in this work include:

  • What are the best ways of supporting a young person who has incurable cancer?
  • How can parents/carers/siblings/partners be best supported following the death of a young person with cancer?
  • How should healthcare professionals communicate with young people with incurable cancer to improve quality of life and patient experience?
  • What are the factors that should determine when to stop treatment when the young person cannot be cured?
  • What methods, techniques or strategies for communication can help young people with incurable disease to talk with their family and friends about their situation?
  • How do young people with incurable disease choose their preferred place of death?
  • What are the most effective ways of supporting a friend with incurable disease?

GCT Study Group priorities

Deliver an epidemiological and clinical study on GCTs in older patients. 

Incidence rates of testicular cancer have been increasing steadily in recent decades for unknown reasons. An increasing proportion of new cases present in men of 50 years of age and older rather than in the expected young adult group.

Treating metastatic disease in older age, with intensive, potentially curative, platinum-based chemotherapy regimens that have largely been tested in young men poses challenges, for example gastroenteric toxicity, renal impairment, peripheral neuropathy, myelosuppression and hearing loss, several of which are more common with advancing age. Consequently, dose reductions and delays may be more common, compromising dose intensity and likelihood of cure. There is little UK data regarding these patients.

The aim of this epidemiological study will be to determine the incidence, clinico-pathological features and treatment of late onset (>50 years) testicular GCT to potentially improve management and outcomes. A request will be made to interrogate the UK National Data Registry to extract information on older germ cell patients with the intension to use the information gathered from the epidemiological study to design a clinical study specifically addressing the needs of this patient group.

Deliver the THERApy de-escalation trial for TESTicular cancer (THERATEST).

THERApy de-escalation in TESTicular cancer (THERATEST) is an observational cohort study of patients receiving SOC treatments (combination chemotherapy or radiotherapy) or de-escalated treatments (primary rRPLND or Carboplatin AUC10) treatments for stage II seminoma. The main objective of the study is to demonstrate feasibility of recruitment/retention.  Secondary objectives are the following:

  • To assess HRQoL, sexual function, oncological outcomes, chemotherapy usage, complications, impact on daily life, and costs for all patients.
  • To generate preliminary comparative evidence for rRPLND and Carboplatin AUC10 as therapy de-escalation strategies against standard of care treatments.
  • To understand patient and clinician perceptions of consent and willingness for randomisation to treatments (BEP, radiotherapy, Carboplatin AUC10, rRPLND as well as open RPLND) that may be tested in future cohort-embedded studies.
  • To establish a framework to test future therapy de-escalation strategies for other “good risk” TGCT groups.

Deliver a multi-intervention study in seminoma. 

Use of extensive surveillance imaging in early-stage disease and cisplatin and bleomycin containing regimens for advanced seminoma testicular cancer may not always be warranted. Surveillance imaging exposes young patients to radiation and incurs significant costs and chemotherapy in this young patient group can be associated with long-term toxicity risks. Because of this, we aim to identify treatments for seminoma that reduce or avoid the use of more intensive treatments/management approaches whilst maintaining excellent outcomes (DFS >90% and 5yr OS >97%). We will design a comprehensive and inclusive platform for seminoma patients which will address multiple questions through a number of single arm and randomised comparisons.

Identify key questions in female germ cell cancer research and design a trial to address areas of unmet need.

Stakeholders have described that research endeavours in female germ cell cancer are hampered by lack of consistency in definitions and language used to describe different disease entities/histopathological variants. Therefore, the first aim of this priority is to standardise terminology/definitions with a group of clinicians who treat and have a vested interest in research for female germ cell cancer patients. Leading on from this first piece of work, we will identify unmet needs for female germ cell cancer patients and design a trial to address the resulting areas of unmet need.