The challenge of rare cancers

Programme stream(s): Treatment

Chair: Richard Adams, University of Cardiff, UK
Presenter: Charleen Chan Wah Hak, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, UK
Speaker: Matt Sydes, University College London, UK
Speaker: Sheela Rao, Royal Marsden Hospital, UK
Speaker: Steve Nicholson, International Rare Cancers Initiative in Penile Cancer, UK

2:00 pm-4:00 pm

Room: Alsh

1. Richard Adams, Introduction
2. Charleen Chan Wah Hak, Emergency Etoposide-Cisplatin (Em-EP) for patients with germ cell tumours (GCT) and trophoblastic neoplasia (TN)
3. Matt Sydes, Issue around clinical research and methodologies to approach optimising evidence and informing best practice
4. Steve Nicholson, InPACT trials and tribulations
5. Sheela Rao, InterAACT trial in metastaic anal cancer
6. Panel discussion

The challenges of rare cancer: Time for change
Speaker: Richard Adams
Affiliation: Cardiff University


Are all cancers becoming rare? How will we cope with the increasing compartmentalization of cancers in an era of ever increasing data? We will discuss rare cancers in the context of clinical trials, exploring practical issues of trials design and collaboration on an international scale as well as exploring the successes and how they have been achieved

Emergency Etoposide-Cisplatin (Em-EP) for patients with germ cell tumours (GCT) and trophoblastic neoplasia (TN)
Speaker: Charleen Chan Wah Hak
Affiliation: Charing Cross Hospital, Imperial College Healthcare NHS Trust, London


Etoposide (E) at 100 mg/m2 combined with Cisplatin (P) at 20 mg/m2 is an induction 2-day regimen embedded in our clinical practice for patients with both advanced GCT and TN at high risk of early death. We evaluated 24/7 Em-EP administration to this combined cohort at our Emergency Cancer Treatment Centre (ECTC).


Patients who received Em-EP between 1st January 2012 and 31st December 2016 were identified from electronic databases at Imperial College Healthcare NHS Trust. Data collected included patient demographics, treatment details and clinical outcome.


Em-EP chemotherapy was administered in the emergency setting to 104 patients, predominantly young adults (median age 35, range 17-71).  Half the cases (n=52) were GCT: 22 male (6 seminomas, 16 non-seminomas); 30 female (2 dysgerminomas, 28 non-dysgerminomas). The other 50% (n=52) were treated for TN: 48 gestational (GTN) and 4 non-gestational. Primary disease sites included: uterine (n=44, 42%), gonadal (n=41, 39%), extragonadal (n=10, 10%) and unknown (n=9, 9%). Most patients received Em-EP for a new cancer diagnosis (n=100, 96%), within 24 hours (n=93, 89%) and out-of-hours (n=74, 70%). 66 patients (63%) were symptomatic, 51 (49%) had high-burden disease and 9 (9%) required Intensive Care Unit admission. The prevalence of neutropaenic sepsis was 5%. 102 patients (98%) remained alive at 4 weeks after their first Em-EP administration. At follow-up (median 9 months, range 0-64 months), overall survival for patients who received Em-EP was 81%, higher in TN (92%) than for GCTs (69%; OR 0.19, p=0.0053, 95% CI 0.06-0.61).


Em-EP represents a standard approach at our ECTC for the initial management of high-risk patients with both GCT and TN. Despite the potentially fatal complications encountered in the acute setting, early mortality with Em-EP is low. Its efficacy within a prospective cohort and in other platinum-sensitive malignancies requires further evaluation.

Designing trials in smaller populations
Speaker: Matthew Sydes
Affiliation: MRC Clinical Trials Unit at UCL


How should we approach trial design when the ideal sample size is considered larger than the number of participants that can be recruited in a reasonable time frame? We present an ordered framework for designing randomised trials, staying with the frequentist approach well accepted and understood in large trials, that includes small alterations to the design parameters. The first step should always be to attempt to extend collaborations, consider broadening eligibility criteria and increase the accrual time or follow-up time. The second set of ordered considerations are the choice of research arm, outcome measures, power and target effect. If the revised design is still not feasible, in the third step we propose moving from two- to one-sided significance tests, changing the type I error rate, using covariate information at the design stage, re-randomising patients and borrowing external information. We discuss benefits from some proposals and warn against others. This framework would allow appropriate evaluation of treatments when large-scale phase III trials are not possible, but where the need for high-quality randomised data is as pressing as it is for common diseases.