A Review of the posters and papers at CTOS
The CTOS (Connective Tissue Oncology Society) meeting in Montreal had about 250 attendees. It was held as a single plenary session (no concurrent sessions) in a hotel ballroom setting. There was also a small poster session. This is my report on those scientific presentations that I attended at the meeting. Other LRG attendees will report on the LRG-sponsored discussions (Friday early morning meeting with Jaap Verwiej, Netherlands; Friday morning pediatric GIST meeting; Saturday evening meeting with Dr. Fletcher, etc.) and LRG outreach activities. In general, GIST was a very hot topic at the CTOS meeting, and the focus of numerous presentations.
Posters:
1. One of the posters (Blay et al.)
described the results of a randomized
clinical trial study in France, in which
glivec treatment was stopped in GIST
patients who had been treated with the
drug. The objective was to see whether
continued treatment (for the patient's
lifetime) is advisable. The results
were, in retrospect, obvious: the rate
of disease progression was drastically
higher in the patients who stopped
glivec. This effect was so dramatic that
the trial was stopped and all the
remaining patients were returned to
glivec treatment.
2. Martin Blackstein et al. (Mt. Sinai, Toronto) put up a poster entitled “Neoadjuvant imatinib therapy for rectal GISTs”. Three cases of rectal GIST were treated with glivec prior to surgery (neoadjuvant treatment). The study concluded that this is an effective treatment approach; glivec induced debulking of the tumours had allowed better surgical outcomes, with subsequent resection (surgery) allowing preservation of the anal sphincter.
3. A poster from a group in the UK reported a case study of blood calcium levels and cramps/ spasms as side effects of glivec treatment. (Serum calcium level and involuntary movements in patients treated with imatinib for GIST, Jamal M Zckri et al) concluded that "Treatment with imatinib (glivec) for GIST is associated with statistically significant reductions in serum calcium. This may account for the high reported incidence of myalgia and muscle cramps in these patients."
Oral Presentations:
1. Acquired resistance to imatinib in
progressive GISTs due to multiple
synchronous kinase mutations in
different exons of kit. Dr Peter
Hohenberger from the Surgical Oncology
section of Mannheim University,
Heidelberg, Mannheim, Germany
representing a team from Germany,
presented on secondary resistance to
imatinib in GIST. They found that
Imatinib treatment of GIST may lead to
secondary resistance to new acquired KIT
mutations in addition to the primary
mutation. In primary tumors with an Exon
9 mutation GIST secondary mutations were
noted in exon 17. In primary tumors with
exon 11 mutatations GIST secondary point
mutations were noted in exons 13, 14 and
17.
2. Early and late resistance to imatinib in advanced GIST are predicted by different prognostic factors: an analysis of the EORTCISGAGITG randomized trial; M Van Glabbeke et al. This report from a large international consortium, including some of the leading European authorities (Verweij, Oosterom, Judson) was of considerable interest. Dr. Van Glabbeke presented the paper. The hypothesis was that the biological mechanisms of resistance to glivec may differ between the cases of “early” versus late” development of resistance. They used their clinical trial database and studied the characteristics of 116 cases of early drug resistance/ progression (among 934 atrisk patients) and 347 cases of late drug resistance/ progression (among 818 at-risk patients). They tested whether various factors biological and treatment variables correlated with risk of resistance.
Lower dose was significantly (p < .01) correlated with late development of resistance but not with early resistance. Low hemoglobin levels upon entry correlated with poorer response; mechanisms for this effect might include hemoglobin effects on drug pharmacokinetics or a correlation between hemoglobin levels and disease state. Another factor that correlated with both early and late resistance was high blood granulocyte count, perhaps, again, due to more advanced disease state or inflammation.
Larger tumours showed poorer response/ more resistance, especially beyond 18 months of treatment. With respect to site of origin, results were better for stomach than for bowel. The authors concluded that factors affecting resistance do indeed differ between early and late resistance. With the possible exception of patients with small bowel primary tumours, dose is an important factor in late resistance, expecially for tumours with less-common sites of origin. In the question period, one doctor asked whether the apparent effect of tumour site of origin might in fact be an effect of exon position of the kit mutation, since that factor is strongly correlated with tumour site of origin, and Dr. Van Glabbeke agreed that this was likely. (exon 9 mutations in GIST occur almost exclusively in the small bowel and not in other sites),
3. The last GIST talk in the session was the LRG presentation: Disease progression in patients with metastatic GIST receiving gleevec (imatinib): the effect of drug dosage P Barckett; J Call; P D Josephy; N J Scherzer; R Singleton The Life Raft Group. Our paper was well-received, and drew compliments from many of the doctors present.
Advocacy Groups: This was the very last session at CTOS 2004, but the attendance was good, nonetheless. Presentations were given by Norman Scherzer which focused on the history and role of LRG; by Jody Cummings, Executive Director, the Sarcoma Foundation, which focused on supporting research projects and by David Murphy of the Sarcoma Alliance, which focused on providing patient support.
By David Josephy, PhD
