Annual Meeting Proceedings Part 1 - American Society of Clinical ...

652s Sarcoma
10088 General Poster Session (Board #53A), Sun, 8:00 AM-12:00 PM
Diagnosis and initial evaluation of patients with gastrointestinal stromal
tumor (GIST): An observational study of 1,226 patients. Presenting Author:
Jonathan C. Trent, University of Miami Sylvester Comprehensive Cancer
Center, Miami, FL
Background: The GIST registry (reGISTry) is an observational database
designed to determine diagnostic method and evaluation of GIST patients
outside of clinical trials. We previously described differences in treatment
of patients in community versus academic centers (Pisters, Ann Oncol
2011;22:2523-9). Herein we present distinct differences in the diagnosis
and initial evaluation of patients with GIST. Methods: The analysis cutoff
date was May 2010. Patient demographics, presenting symptoms, diagnostic
methodology, and KIT and PDFGRA mutations were described. For
localized tumors, size and mitotic index (MI) were collected. Results: 1226
patients were included in this analysis. Initial diagnosis was most commonly
made by surgeons (54.6%) and gastroenterologists (15.7%). Primary
management decisions were made at time of diagnosis by medical
oncologists (53%) and surgeons (53%) (sum �100% due to �1 responses/
site). 84% were symptomatic at diagnosis, while 16% were diagnosed
incidentally. Diagnostic procedure was performed during surgery (75%)
and/or by endoscopy (22%) or interventional radiology (11%) using
percutaneous core biopsy or fine needle aspirate. Initial diagnostic imaging
was by CT scan (76%), endoscopy (25%), ultrasound (12%), or a
combination. Most primary GISTs were located in the stomach (55%) or
small intestine (28%). At diagnosis, localized and metastatic disease was
seen in 83% and 17% of patients, respectively, with metastases mainly in
the liver (62%) and/or peritoneum (36%). KIT immunostaining was
performed in 93% of patients, with 98% positive. Mutation analysis was
carried out in 8% of cases (57% KIT exon 11 and 12% exon 9 mutations).
Of localized primary tumors, 52% were �5 cm in size and 23% had �5
mitoses per 50 high-power fields. Conclusions: We found that initial
diagnosis is made by several different modalities. The majority of GIST
patients are managed by medical and surgical oncologists. Most patients
with localized tumor were at intermediate risk of recurrence and would be
considered for adjuvant imatinib therapy.
10090 General Poster Session (Board #53C), Sun, 8:00 AM-12:00 PM
Outcomes of multivisceral resection of gastric gastrointestinal stromal
tumors. Presenting Author: Sabha Ganai, University of Chicago Medical
Center, Chicago, IL
Background: Despite the recent introduction of imatinib and laparoendoscopic
techniques to the management of gastric gastrointestinal stromal
tumors (GISTs), outcomes remain uncertain in the setting of multivisceral
involvement. Methods: We conducted a retrospective review of 73 consecutive
patients who underwent resection of gastric GISTs from October 2002
through December 2011. Median follow-up was 22 months (interquartile
range [IQR] 6-37). Results: Patients were 51% female, with a mean age of
65 � 12 years and BMI of 30 � 8 kg/m2 . Patients undergoing multivisceral
resection (n�14) had a longer interval from diagnosis to surgery (7.3 [IQR
1.9 – 15.0] vs. 1.3 [IQR 0.7-4.2] months, p�0.01), greater use of
neoadjuvant imatinib (64% vs. 3%, p�0.0001), and greater preoperative
tumor size (12 � 8 vs. 4 � 3 cm, p�0.0001) in comparison to gastric-only
resections (n�59). Patients were less likely to be managed laparoscopically
(7% vs. 71%, p�0.0001), had a longer operative time (310 � 117
vs. 145 � 62 min, p�0.0001), and were less likely to be R0 (71% vs.
98%, p�0.001). While patients undergoing multivisceral resection were
more likely to have a pathological complete response to therapy (29% vs. 0,
p�0.001), they were also more likely to have metastatic disease present
(29% vs. 0, p�0.001). Hospital length of stay was greater (median 8 [IQR
6-9] vs. 3 [IQR 2-6] days, p�0.0001). There were no significant differences
in grade or mitotic index between groups. There was greater use of
adjuvant imatinib (64% vs. 25%, p�0.05). Overall survival was less in
patients undergoing multivisceral resection (64% vs. 87% at 3 years,
p�0.05), as was disease-free survival (52% vs. 71% at 3 years, p�0.05).
Median overall and disease-free survival were 43 and 22 months after
multivisceral resection for gastric GISTs. Controlling for tumor size, grade,
resection status, and the use of neoadjuvant imatinib, multivisceral
resection and use of adjuvant imatinib were both independent predictors of
disease-free survival (p�0.05). Conclusions: Multivisceral involvement is
associated with tumors of greater size and, despite an increased use of
neoadjuvant imatinib, it is associated with poor outcome for patients with
gastric GISTs.
10089 General Poster Session (Board #53B), Sun, 8:00 AM-12:00 PM
Masitinib in imatinib-naive advanced gastrointestinal stromal tumor (GIST):
Five-year follow-up of the French Sarcoma Group phase II trial. Presenting
Author: Axel Le Cesne, Institut Gustave Roussy, Villejuif, France
Background: Masitinib is a tyrosine kinase inhibitor that in vitro has greater
activity and selectivity than imatinib against KIT. This multicenter, open
label, phase 2 study evaluated efficacy and safety of masitinib as a first-line
treatment of advanced GIST. Initial results with a median follow-up of 34
months, were previously reported in EJC 2010. We present here 5-year
follow-up data from the same series with updated safety and survival data.
Methods: Imatinib-naïve patients (pts) with inoperable, advanced GIST
received oral masitinib (7.5 mg/kg/day) until progression, refusal or
toxicity. Results: Thirty pts with a median age of 58 years (60% of males)
were included from 06/2005 to 04/2007 in 5 institutions. At the cut-off
date of 13/09/2011, 7/30 pts (23%) were still under treatment with
median follow-up of 65 months and the median overall survival (OS) had
not yet been reached (NR). The 5-year OS rate was 61.5% (95% CI
[41.1;76.6]) (see Table). Among patients with confirmed KIT exon 11
mutation, 8/9 pts (89%) were still alive with one pt having died from
non-treatment related causes (surgical complication) following a complete
response while receiving masitinib. No additional progressions have been
reported giving a total of 14 events (13 progressions and 1 death). Updated
median PFS was 41.3 months (95% CI [17.5;53.8]).No additional grade
3/4 adverse events have been reported. Conclusions: Long term results of
masitinib confirm an interesting activity with prolonged PFS and OS. The
median PFS rate in masitinib compares very favorably to that of imatinib,
which is reported as 18 months (JCO 26:626, 2008). The 5-year OS rates
for masitinib in the overall and exon 11 populations also compare favorably
to imatinib, both of which are reported at �50% for imatinib (JCO 26:626,
2008; JCO 28:1247, 2010). These results support the head to head
comparison with imatinib in the currently ongoing phase 3 randomized
clinical trial in first line advanced GIST pts.
All (N�30) Exon 11 (n�9)
Median OS (months) [95%CI] NR [53;NR] NR [65;NR]
Month-36 86.5% [68.0;94.7] 88.9% [43.3;98.4]
48 76.2% [56.4;87.9] 88.9%
60 61.5% [41.1;76.6] 88.9%
72 55.9% [34.7;72.6] 71.1% [23.3;92.3]
10091 General Poster Session (Board #53D), Sun, 8:00 AM-12:00 PM
Single-dimension CT measurements with RECIST 1.1 to evaluate liver
metastases in GIST patients on imatinib. Presenting Author: Gaia Schiavon,
Department of Medical Oncology, Erasmus University Medical Center -
Daniel den Hoed Cancer Center, Rotterdam, Netherlands
Background: Tumor response assessment to therapy is crucial in oncology,
both in daily practice and research.We analyzed the morphology of liver
metastases (LM) in gastrointestinal stromal tumors (GIST). Aims were to 1)
determine whether uni-dimensional measurements of tumor lesions (according
to RECIST 1.1) are accurate reflections of their volumes and 2)
estimate eventual bias in volume change calculations, as introduced by
using only the longest diameter. Methods: 78 GIST patients with LM were
evaluated at baseline (n�139 lesions), 3 (n�129), 6 (n�128), and 12
months (n�108) after imatinib therapy. LM were segmented semiautomatically
on standard CT scans. All measurements at baseline were
obtained by 2 independent investigators and agreement between observers
was assessed with Bland-Altman plots. Values for segmented volume (Vs;
mL), maximum transaxial diameter (MTD; mm), and elongation value (EV,
defined as 1 - [width/length], where EV of 1 � fully ellipsoidal and 0 � fully
spherical) were reported for each lesion at several time-points. A calculated
volume (Vc) of each LM was also generated using the MTD, with the
hypothesis that metastases were fully spherical. Results: At baseline, 44%
(61/139) of the LM was spherical and 56% (78/139) was ellipsoidal. Their
EV ranged from 0.08 to 0.94 (mean, 0.53�0.17). During treatment,
overall 42% of the lesions kept their morphology (spherical or ellipsoidal)
and the other half changed from spherical to ellipsoidal or vice versa. At
baseline, there was strong inter-observer agreement in the determination of
Vs, with mean inter-observer variability of 1.5% (95% CI, -14.5% to
17.5%). The difference between Vs and Vc was highly significant
(P�0.0001). Vc overestimates the actual volume of 35% (95% CI, -26%
to 95%). Conclusions: LM are not always spherical and can change their
morphology during imatinib therapy. Therefore, a lesion’s single largest
trans-axial dimension, as used in RECIST 1.1, is not an accurate surrogate
of its actual volume. Further studies are warranted to fully understand the
clinical impact of these findings and to assess whether we should apply
different criteria for response assessment to therapies in solid tumors.
Visit abstract.asco.org and search by abstract for the full list of abstract authors and their disclosure information.