Gynaecological Cancer InterGroup (GCIG)
Meeting Saturday 10th October 2009
Adriatic Room, Continental Hotel, Belgrade
Present:
Michael Birrer
Iain McNeish
.
.
.
.
mbirrer@partners.org
i.a.mcneish@qmul.ac.uk
(GOG)
(NCRI)
1.
Minutes of the previous meeting were shown and discussed.
It was noted that the e-mail list from the ASCO meeting in May 2009 was probably
not accurate and did not reflect the participants present in Belgrade. Several present
had not received minutes from May 2009 nor paperwork relevant for the current
Working Group meeting. Every effort will be made to ensure that participants receive
minutes of current meeting.
2.
New translational research efforts
The meeting opened with a discussion of translational research projects going on
within GCIG trials. It was noted that the upcoming GOG262 (multicentre phase III
trial of weekly dose dense carboplatin and Taxol +/- bevacizumab vs standard
carboplatin + Taxol + bevacizumab) and COG213 (IP chemotherapy) trials offered
excellent opportunities for novel translational studies. It was noted, as before, that
translational research is frequently added to protocols at a very late stage and
shoulw be considered at a much earlier stage in protocol development. A discussion
took place as to how best to obtain useful clinical samples from multi-centre trials
using the up-coming NCRI trial of weekly paclitaxel and Src inhibitor as an example.
It was agreed that that usefulness of samples collected within multi-centre trials was
often in inverse proportion to the feasibility of collection. Peripheral blood was easy
to obtain but sometimes gave little meaningful information, for example on inhibition
of kinase activity within tumours. A debate took place as to whether it was possible
to mandate tumour biopsies within multi-centre trials in relapsed cancer, when there
was no clinical indication for biopsy. Several participants commented that patients
were frequently willing to consent for research biopsies but pathologists and
radiologists were sometimes less amenable.
3.
Pharmacogenomics
A brief presentation was made on the proposed pharmacogenomics study led by NCI
and GOG. Hypothesis is that individual and population genetics may affect response
to primary chemotherapy, toxicity and QoL outcomes in ovarian cancer. The stdy
would require genomic DNA from women with stage III/IV ovarian cancer, with wellannotated clinical data. It was noted that the Riken Institute, University of Tokyo, had
confirmed that they would perform analysis at no charge. A discussion followed as to
whether whole blood was required for DNA extraction or whether other sources, such
as buccal smears, would be a suitable alternative. It was felt that whole blood was
likely to yield higher quality DNA in sufficient quantities for the type of GWAS
analyses that were planned. Members present were encouraged to consider
providing samples from previous phase III trials if possible.
4.
Clear cell study
Three presentations followed from the JGOG. Dr Aikou presented data from CGH
analysis of ovarian cancers highlighting potential gene amplifications in ovarian
cancer, including CCL4 on chromosome 17. Dr Matsumura presented data on
polymorphisms of the UGT1A1 gene in the metabolism of irinotecan. Four
polymorphisms were presented (*60, *28, *6, and *27). omozygosity for UGT1A1*6
was associated with a high risk of severe neutropenia, although no data were
available to correlate neutropaenia or any of the polymorphisms with response rates.
Polymorphisms of *6 and *28 were also associated with hyperbilirubinaemia. Finally,
Dr Susuma presented results of expression array analysis of clear cell carcinoma cell
lines and tumours. The data presented clearly identified that clear cell ovarian
carcinoma was a separate entity on hierarchical clustering from serous and
endometrioid sub-types. Genes associated with kidney development were
prominent. It was noted that clear cell carcinomas of the ovary and kidney
demonstrated similar expression profiles. One gene identified was HNF-1, which
was also associated with endometriosis. Data were presented on potential inhibition
of HNF-1-associated pathway activation with sorafenib were presented, including
activity in subcutaneous clear cell carcinoma xenografts. Discussion followed on a)
the prevelance of clear cell carcinoma in Japanese vs European and American
women, b) why the rate of endometriosis and clear cell carcinoma was rising in
Japan and c) the potential for future clinical studies in clear cell carcinoma involving
patients with tumours of both ovarian and renal origin given their clear similarities on
expression profiling.
5.
Mucinous ovarian cancer trial
It was noted that the upcoming mEOC/GOG241 trials in mucinous ovarian cancer
offer a hige opportunity to address translational questions in this subtype. Time
prevented a full discussion but participants were sent the full GOG protocol.
6.
Any other business
A full list of participants was taken and minutes will be distributed to all present.
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