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

Lung Cancer—Non-small Cell Local-Regional/Small Cell/Other Thoracic Cancers
7072^ General Poster Session (Board #38G), Sat, 1:15 PM-5:15 PM
Size distribution and metastasis in discarded intrapulmonary lymph nodes
(LN) after lung cancer resection. Presenting Author: Laura Elizabeth Miller,
University of Tennessee Health Science Center, Memphis, TN
Background: Lymph node (LN) status is the most important prognostic
determinant after resection of lung cancer. 18% of a SEER cohort and 12%
of a Memphis cohort had no LNs examined (pNx). Patients with pNx have
inferior survival to T-category matched pN0 patients with at least 1 LN
examined. The optimal number of LN needed to safely declare a patient
pN0 may be �10. Less than 20% of resections in SEER achieve this. We
hypothesized that a significant number of intrapulmonary LNs are left
unexamined and some may harbor metastatic disease. We report the size
characteristics of materials examined in a re-dissection protocol to test this
hypothesis. Methods: Prospective study of lung resection specimens redissected
after signout of the final pathology report. Remnant lung material
was dissected with thin cuts and all LN-like material was retrieved for
microscopic examination, irrespective of size or location. The size of
non-LN tissue, LN without metastasis and LN with metastases were
compared using the Wilcoxon-Mann-Whitney test. Results: 112 specimens
were examined and 1,094 LN-like materials were retrieved. 749 (69%)
proved to be LN tissue. 71 (10%) LNs retrieved had metastasis. Non-LN
tissue was significantly smaller than LN tissue (p�0.0001). LNs with
metastasis were significantly larger than those without metastasis (p
�0.0001). 60% of materials �2cm were LNs with metastasis. 7% of
materials �1cm were LN with metastasis. 52% of LNs with metastasis,
and 55% of LNs without metastasis measured from 0.5 to 1.5cm (Table).
Majority of LNs �2cm had metastatic disease, but 40% did not; a notable
proportion of LNs with metastasis were small. Nearly equal percentages of
LNs with and without metastasis were found in the range of 0.5-1.5cm.
Conclusions: Statistical differences in size between lymph nodes with and
without metastasis is clinically meaningless due to broad overlap. LN size
alone is not an adequate predictor of LN metastasis.
Size (cm) Size range (cm), n (%)
Mean Median 0-0.5 >0.5-1 >1-1.5 1.5-2 >2
Non-LN, n�345 0.48 0.4 252 (73) 66 (19) 17 (5) 10 (3) 0 (0)
LN without 0.69 0.6 281 (42) 302 (45) 72 (11) 15 (2) 8 (1)
metastasis
n�678
LN with 1.32 1.2 8 (11) 20 (28) 17 (24) 14 (20) 12 (17)
metastasis
n�71
7074 General Poster Session (Board #39A), Sat, 1:15 PM-5:15 PM
Factors influencing recurrence following anatomic lung resection for
non-small cell lung cancer. Presenting Author: Rodney Jerome Landreneau,
University of Pittsburgh Shadyside Medical Center, Pittsburgh, PA
Background: Anatomic lung resection provides the patient with the best
chance for cure in the setting of early-stage non-small cell lung cancer
(NSCLC). Despite complete (R0) resection, up to 20-30% of patients will
develop recurrent disease. In the current study, we analyze the impact of
surgical and pathologic variables upon recurrence patterns following
anatomic lung resection for clinical stage I NSCLC. Methods: A total of
1,192 patients (394 segmentectomies, 805 lobectomies) with clinical
stage I NSCLC were evaluated. The primary outcome variable was recurrence.
Multivariate analysis was performed based upon clinical (age,
gender, comorbidities), surgical (operation, approach, surgical margin) and
pathological (pleural invasion, tumor size and histology) variables. Predictors
of recurrence were identified by proportional hazards regression.
Differences in recurrence patterns between groups are illustrated by log
rank tests applied to Kaplan-Maier estimates. Results: A total of 243
recurrences (20.3%) were recorded at a mean follow-up of 35.6 months
(71 locoregional, 172 distant). There was no significant difference in
recurrence patterns when comparing segmentectomy and lobectomy.
Multivariate analysis demonstrated that a margin:tumor ratio � 1, angiolymphatic
invasion and the presence of only mild-moderate tumor inflammation
were predictors of recurrence risk. Conclusions: Recurrence following
anatomic lung resection is influenced predominantly by pathological
variables (tumor size, angiolymphatic invasion, tumor inflammation).
Optimization of surgical margin in relation to tumor size may improve
outcomes. Extent of resection (segmentectomy vs. lobectomy) does not
appear to have an impact on recurrence-free survival when adequate
margins are obtained. These data have implications regarding the potential
use of adjuvant therapy in selected Stage I patients at high risk for
recurrence.
Segmentectomy
(n�394)
Lobectomy
(n�805) P value
Recurrence 81(20.4%) 162 (20.1%) 0.88
Locoregional 23 (5.9%) 48 (6.0%) 1.00
Distant 58 (11.9%) 114 (14.1%) 0.79
5-yr freedom from recurrence 69% 70% 0.53
469s
7073 General Poster Session (Board #38H), Sat, 1:15 PM-5:15 PM
N0321: A phase II study of bortezomib, paclitaxel, carboplatin (CBCDA),
and radiotherapy (RT) for locally advanced non-small cell lung cancer
(NSCLC). Presenting Author: Steven E. Schild, Mayo Clinic, Scottsdale, AZ
Background: In preclinical studies, combinations of bortezomib and RT
result in synergistic tumor killing (Cancer Chemother Pharmacol. 2007;59:
207-15). Our group reported the results from the phase I portion of this
study previously (J Clin Oncol. 200;28 (suppl; abstr 7085)). Based on
these data, we undertook a phase II study of bortezomib in combination
with paclitaxel/CBCDA and RT. Methods: Based on results from our
previously reported phase I trial, systemic therapy included bortezomib
(1.2 mg/m² IV days 1,4,8,11), paclitaxel (175 mg/m² IV day 2), and
carboplatin (CBCDA; AUC�6 day 2) given every 3 weeks for 2 cycles.
Thoracic radiotherapy (RT) included 60Gy/30 daily fractions starting day 1.
The primary endpoint was the 12-month survival rate. If 41 or more of these
60 patients (68%) were alive at least 12 months after study entry, the trial
would be deemed as positive and further study would be warranted. Results:
27 pts were enrolled to the phase II portion: M/F�17/10; stage IIIA/
IIIB�13/14; ECOG PS 0/1�9/18; and median age: 58 (range 43-79). 18
pts (67%) completed therapy per protocol. At a planned interim analysis,
23 of 26 evaluable patients (88.5%, 95% CI: 70-98%) survived for at least
6 months, which exceeded the boundary of 21 or more needed to continue
to full accrual. This trial could have continued per protocol, but was closed
early due to slow accrual. With a median follow-up of 15.0 months in the
17 patients still alive, the 12-month survival rate was 71% (95% CI: 49 –
85). The median OS was 19 months (95% CI: 11 – no upper). Grade 3 or
higher adverse events (regardless of attribution) were reported in 22 (82%)
patients. Grade 4/5 adverse events were reported in 15 (56%) patients.
There was one grade 5 event (pneumonitis). The most common (5 or more
patients) grade 3/4 adverse events were fatigue (22%), leukopenia (63%),
neutropenia (67%), and thrombocytopenia (44%). Conclusions: The addition
of bortezomib resulted in high levels of severe hematologic toxicity, but
also demonstrated evidence of activity with a 12-month survival rate of
71% and a median OS of 19 months. Further testing of this regimen in a
larger study appears warranted.
7075 General Poster Session (Board #39B), Sat, 1:15 PM-5:15 PM
The Lung Cancer Symptom Scale (LCSS) as a prognostic indicator of overall
survival in malignant pleural mesothelioma (MPM) patients: Post hoc
analysis of a phase III study. Presenting Author: Ping Wang, Eli Lilly and
Company, Indianapolis, IN
Background: To determine the patients likely to benefit from therapy,
clinicians seek factors associated with outcomes. This analysis investigates
prognostic effect of baseline patient-reported symptoms on overall survival
(OS) in the presence of demographic/clinical factors among MPM patients.
Methods: Intent-to-treat patients (N�448) were included in the analysis.
LCSS consists of 6 symptom items and 3 general items, each ranging from
0 (no symptoms) to 100 (worst). Average symptom burden index (ASBI)
was the mean of 6 symptom items. Patients were classified into subgroups
based on ASBI: low symptom burden (LSB; ASBI�25) and high symptom
burden (HSB; ASBI �25). Univariate Cox models were used to determine
the prognostic effect of 7 demographic/clinical factors, 9 LCSS items, and
ASBI on OS. Multivariate Cox model was used to determine the prognostic
effect of ASBI in the presence of 7 demographic/clinical factors. Kaplan-
Meier curves of OS were generated for patients with LSB and HSB and
compared using both univariate and multivariate Cox models. Results: In
the univariate analysis, significant prognostic effects on OS were observed
for baseline Karnofsky performance status (KPS; 90-100 vs. 70-80, hazard
ratio [HR]�0.45, p�0.0001) and baseline stage (I/II/III vs. IV, HR�0.63,
p�0.0001). In addition, significant prognostic effects were observed for 5
LCSS symptom items (anorexia, cough, dyspnea, fatigue, and pain), 3
LCSS general items (interference with activity level, symptom distress, and
quality of life; HRs�1.08-1.20 for every 10 points worsening, all p�0.02),
as well as ASBI (HR�1.32, p�0.0001). In the multivariate Cox model,
ASBI remained a significant prognostic factor of OS (HR�1.22, p�0.0001),
along with baseline KPS and stage. Patients with LSB (N�265) had
significantly better OS than those with HSB (N�181) (12.9 vs. 6.9
months, HR�0.46, unadjusted p�0.0001; HR�0.59, p�0.0001 adjusted
for the 7 demographic/clinical variables). Conclusions: The results
suggest that baseline patient-reported symptoms as measured by LCSS
provide distinct prognostic information in the presence of demographic and
clinical measures in MPM.
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