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

Lung Cancer—Non-small Cell Local-Regional/Small Cell/Other Thoracic Cancers
7104 General Poster Session (Board #42G), Sat, 1:15 PM-5:15 PM
A prospective, phase II trial of induction chemotherapy with docetaxel/
cisplatin for Masaoka stage III/IV thymic epithelial tumors. Presenting
Author: Silvia Park, Division of Hematology-Oncology, Department of
Medicine, Samsung Medical Center, Sungkyunkwan University School of
Medicine, Seoul, South Korea
Background: Thymic epithelial tumors (TETs), thymoma and thymic carcinoma,
are the most common tumor of the anterior mediastinum. Initial
complete resection is the most powerful prognostic indicator of survival.
However, it is obviously related to stage. Here, we report the result of a
prospective phase II study of neoadjuvant docetaxel/cisplatin in patients
with locally advanced TETs. Methods: In this open-label, phase II, nonrandomized
study, patients with histologically proven, Masaoka stage III/IV
TETs at presentation were enrolled. Patients received docetaxel 75mg/m2 I.V for 1 hr, followed by I.V cisplatin 75mg/m2 over 1.5hr on day 1 of every
3 week. After 3 cycles of chemotherapy, subsequent surgical resection was
performed, if resectable. Results: From March 2007 to July 2011, a total of
27 TETs patients were entered into the trial. The median age was 54
(range, 15-68), and Masaoka stage at presentation was III (n�8, 29.6%),
IVA (n�17, 63.0%), and IVB (n�2, 7.4%). Histologic type by the WHO
includes type B1 (n�2, 7.4%), B2 (n�3, 11.1%), B3 (n�5, 18.5%), and
thymic carcinoma designated as type C (n�16, 59.3%). After completion
of neoadjuvant chemotherapy, 17 (63.0%) achieved PR and 10 (37.0%)
had SD. Nineteen patients (70.4%) underwent surgical resection, and 8
patients did not (surgeons’ decision, n�5; patients’ refusal, n�2; radiation
therapy, n�1). Of the 19 patients undergoing surgical resection, 17
(89.5%) had complete resections and 2 (10.5%) did not. Major side
effects of chemotherapy include grade 3 anorexia (n�1), nausea (n�2),
diarrhea (n�3), alopecia (n�1). After completion of surgical resection,
adjuvant therapy was performed as follows: radiotherapy (RT, n�8),
chemotherapy (CTx, n�6), radiotherapy with chemotherapy (RT � CTx,
n�2) and observation (n�3). Overall, 4yr OS and PFS was 79.4% and
40.6%. Patients with complete resection showed 93.8% of 4yr OS and
50.2% of 4yr PFS whereas patients without complete resection showed
47.6% of 4yr OS and 26.7% of 4yr PFS, respectively (OS, p�0.06; PFS,
p�0.27). Conclusions: Neoadjuvant docetaxel/cisplatin was well tolerated
and feasible, and improved the surgical respectability in patients with
advanced TETs.
7106 General Poster Session (Board #43A), Sat, 1:15 PM-5:15 PM
A 19-gene prognostic GEP signature (DecisionDx-Thymoma) to determine
metastatic risk associated with thymomas. Presenting Author: Yesim
Gokmen-Polar, Indiana University School of Medicine, Indianapolis, IN
Background: The treatment of thymomas is predominantly based on the
stage of disease. Histologic classification is of limited value as all types of
thymomas can give rise to metastases. In order to better predict the
metastatic behavior of these tumors, we performed genome-wide gene
expression analysis and identified a set of genes associated with presence
or absence of metastases. In the current study, we sought to further develop
and validate the gene signature using quantitative RT-PCR analysis.
Methods: Thymomas with archived blocks and long-term follow-up data
were reviewed. This training set study consisted of 50 cases, including 34
cases on which the discovery microarray analysis had been performed. RNA
was extracted from 5 x 10-micron thick sections in a CAP-accredited CLIA
certified laboratory and analyzed by RT-PCR using custom TLDA cards on
an ABI7900HT instrument. Expression data and biostatistical analysis
were performed using GeNorm and JMP Genomics (SAS). Predictive
modeling using Partition Tree Analysis (PTA) and Logistic Regression
Analysis (LRA) was performed. Metastasis-free survival (MFS) was assessed
using Kaplan-Meier analysis. Results: A 19-gene expression profile
(GEP) signature was developed using a cohort of 50 thymomas for
predicting metastasis. PTA yielded ROC of 0.97 (met. accuracy � 96%,
non-met. accuracy � 81%), while LRA yielded ROC of 0.895 (met.
accuracy � 87%, non-met. accuracy � 85%). PTA classification showed
5-year MFS rates of 100% and 31% for predicted low risk (Class 1) and
high risk (Class 2) of metastasis (median MFS � NR and 4.1 yrs, resp.,
P�0.0001 Log-Rank), respectively. LRA showed 5-year MFS rates of
100% and 17% for predicted Class 1 and high risk Class 2 of metastasis
(median MFS � NR and 2.9 yrs, resp., P�0.0001 Log-Rank), respectively.
Analysis of additional cohorts is ongoing. Conclusions: We have successfully
completed development of a 19-gene signature (DecisionDx-Thymoma)
that appears to predict metastatic behavior of thymomas more accurately
than traditional staging. If validated in larger cohort, this signature will
provide insight for the future management of patients with this rare
malignancy.
477s
7105 General Poster Session (Board #42H), Sat, 1:15 PM-5:15 PM
Neoadjuvant treatment of primary inoperable or local recurrent thymoma
with octreotide LAR to improve tumor resectability. Presenting Author:
Berthold Schalke, Department of Neurology, University of Regensburg,
Regensburg, Germany
Background: The therapeutic outcome for unresectable, locally advanced,
malignant thymoma is poor. Most important factor for long-term survival in
thymoma patients is complete resection (R0) of the tumor. The study was
performed to evaluate the efficacy of octreotide LAR plus prednisone in
patients with primary inoperable or local recurrent thymoma to reduce
tumor size. Methods: This was an open label, single-arm study in patients
with inoperable or local recurrent thymoma. Patients were considered
unlikely to achieve R0 resection at enrollment. Octreotide LAR was
administered once every 2 weeks in combination with prednisone. Two
stages were planned according to Fleming’s one sample multiple testing
procedure for phase II clinical trials. The objective of the study was to show
that octreotide LAR is effective in this patient population with respect to
tumor shrinkage. Response was defined as decrease in tumor volume of at
least 20% at month 3 as compared to baseline. Results: 17 thymoma
patients at Masaoka stage III were recruited. Octreotide LAR showed a
response in 15 of 17 patients (88.24%) at week 12. Two patients had
discontinued the study before week 12 due to unsatisfactory therapeutic
effect or adverse events. At Week 12, 5 patients (29.41%) operable for
radical resection. 10 patients (58.82%) were not operable for radical
resection. 16 of 17 patients (94.12%) experienced adverse events (AEs).
The most frequent AEs were gastrointestinal disorders (70.59%), infections
and infestations (64.71%), and blood/lymphatic system disorders
(41.18%). Conclusions: Octreotide LAR was shown to be effective in
patients with inoperable thymoma with respect to tumor shrinkage.Octreotide
LAR was generally well tolerated. The reported AEs are in
accordance with the known safety profile.
7107 General Poster Session (Board #43B), Sat, 1:15 PM-5:15 PM
Factors affecting survival of patients with Masaoka stage IV thymic
epithelial tumors (TET). Presenting Author: Yaman Suleiman, Indiana
University School of Medicine, Indianapolis, IN
Background: Thymoma and thymic carcinoma (TC) are rare tumors, but
represent the most common neoplasms of the anterior mediastinum. The
vast majority of TET present in early stages with little data existing on
factors influencing survival in patients with advanced or stage IV disease.
Methods: A retrospective analysis was performed on patients with confirmed
TET (histology and with tissue blocks) seen at IUSCC diagnosed between
1976 and 2011. Patient demographics including Masaoka stage, histology,
and sites of metastasis were linked with progression free survival (PFS)
and overall survival (OS). Results: Our analysis included 102 patients with
stage IV TET: 50 presented de novo and 52 developed stage IV disease
following primary treatment. When stratified by tumor histology (thymoma
or TC), patients with TC had considerably poorer PFS (p�1.87x10-7 ) and
OS (p�7.72x10-8 ). The median PFS for TC was 13 months (range 4 to 39)
and the MST was 36 months (range 4 to 115). PFS at 5-years was 21% and
0% but the five-year OS was 84% and 29% for thymoma and TC,
respectively. Ten year OS was 55% for patients with thymoma and 0% for
those with TC. Pleural (�3 vs. �3) metastases were significantly associated
with a better PFS (p�0.036) and OS (p�0.0003). The PFS and OS of
patients with lung nodules trended with those with pleural metastasis.
Patients with pleural metastasis and lung nodules sites did considerably
better than those with visceral disease (PFS, p�0.004, OS, p�2.09x10-5 ).
Conclusions: Patients with TC have significantly poorer PFS and OS when
compared to thymoma confirming that TC is a distinct clinical entity from
thymoma. Patients with thymoma may have prolonged survival, despite
having residual disease. Although current staging places patients with
pleural metastasis (Masaoka stage IVA) and those with lung nodules (stage
IVB) as separate categories, our data would suggest that those with lung
nodules have similar survival with those who have pleural metastasis.
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