Volume 90 � Number 1S � Supplement 2014 Digital Poster Discussion Abstracts S213

treatment of patients with non-small cell lung cancer (NSCLC). While

PET/CT is the most accurate imaging modality for this purpose, it has

variable sensitivity (40%-97%) and specificity (60%-96%) due to several

patient, tumor, and technique-specific factors. We hypothesized that

normalizing the LN SUV by using the ratio of the LN to primary tumor

SUVmax (SUVN/T) may be a better predictor of nodal malignancy than

absolute SUVmax alone.

Materials/Methods: We identified 729 patients with newly diagnosed

NSCLC who underwent pathologic LN staging at our institution from

2002-2011. Patients with prior chemotherapy or radiation therapy,

granulomatous disease, or non-skin cancer malignancy were excluded.

The 175 patients who underwent PET/CT within 31 days prior to biopsy

(median 16 days) were included in this analysis. Among these patients,

504 LNs were biopsied and visualized on PET/CT. Receiver operating

characteristic (ROC) curves with area under the curve (AUC) calcula-

tions were used to evaluate SUVmax and SUVN/T for their ability to

predict nodal malignancy. An optimal cutoff to predict nodal malignancy

was determined for each parameter, and defined as the point on the ROC

curve that maximized the sum of the sensitivity and specificity. The

LN short-axis diameter and primary tumor grade, histology, size, and

primary tumor location relative to the LN in question were also

evaluated.

Results: Of the evaluated LNs, 83% were mediastinal and 17% were

hilar, 89% were biopsied by excision, and 11% by aspiration, and 86%

were pathologically benign, and 14% were malignant. The optimal cutoff

value of SUVN/T to predict nodal malignancy was 0.27 (sensitivity 93%,

specificity 87%, AUC 0.926, with a 95% AUC confidence interval [CI]

of 0.890 to 0.961), whereas the optimal cutoff value of SUVmax to

predict nodal malignancy was 2.85 (sensitivity 93%, specificity 82%,

AUC Z 0.925, 95% CI Z 0.889 to 0.961). Sensitivity was > 95% at

SUVN/T < 0.17, whereas specificity was > 95% at SUVN/T > 0.44. For

the subset of patients that had both a primary tumor SUVmax > 6.0 and

LN SUVmax 2.0 e 6.0 (i.e., primary tumors with high FDG-avidity

but LNs with intermediate FDG-avidity), SUVN/T was significantly

more accurate in predicting nodal malignancy (AUC Z 0.839, 95% CI

Z 0.762-0.915) than SUVmax (AUC Z 0.646, 95% CI Z 0.540-0.753).

Conclusions: The ratio of lymph node SUV to primary tumor SUV on

PET/CT is highly predictive of nodal malignancy in patients with newly

diagnosed NSCLC, with SUVN/T being a more accurate parameter than

SUVmax when assessing lymph nodes of intermediate SUV. This N/T ratio

has great potential to improve non-invasive nodal staging in NSCLC if

validated in independent datasets.

Author Disclosure: M.D. Mattes: None. S. Ahsanuddin: None. A. Apte:

None. A.B. Moshchinsky: None. N.P. Rizk: None. A. Foster: None. A.J.

Wu: None. H. Ashamalla: None. J.O. Deasy: None. W.A. Weber: None.

A. Rimner: None.

1136Survival Benefit of Surgery Following Chemoradiation Therapy forStage III NSCLC Is Dependent on Achieving Pathologic NodalClearanceG. Hermann, E. Ziel, P. Bonomi, M. Liptay, W. Warren, G. Chmielewski,

M. Fidler, M. Batus, and D.J. Sher; Rush University Medical Center,

Chicago, IL

Purpose/Objective(s): Patients (pts) with stage III non-small cell lung

cancer (NSCLC) experience high rates of locoregional (LR) and distance

recurrence. Although surgery (S) following chemoradiation therapy (CRT)

has been shown to improve LR control and progression-free survival

(PFS), its impact on overall survival (OS) is unclear. Nodal pathologic

complete response (PCR) at the time of surgery is a strong predictor of

survival, but the optimal management of pts with residual nodal disease is

debated. The objective of this retrospective study was to compare survival

outcomes in pts treated with CRT and CRT + S, focusing on results as a

function of nodal clearance.

Materials/Methods: Pts with stage III NSCLC who were treated with

CRT +/- S at our institution from Dec 2004 through Aug 2012 were

included for analysis. For pts treated with CRT + S, nodal response was

dichotomized into PCR vs not (N-PCR). Overall survival, PFS, and distant

metastases-free survival (DMFS) were determined using Kaplan-Meier

statistics and Cox regression analysis. We determined cumulative in-

cidences of locoregional recurrence (LRR), with death as a competing risk.

Results: A total of 204 pts were eligible for analysis, (69% definitive CRT

and 31% CRT + S). There was a slight female preponderance (51%).

Median age of the whole cohort (WC) was 66 years. Stage distribution for

WC was 52% IIIA and 48% IIIB, and for CRT + S it was 71% IIIA and

29% IIIB. Among CRT + S pts, there were 75% PCR and 25% N-PCR.

Median follow-up for surviving pts was 37.3 months (mo) with a median

OS for WC, CRT, and CRT + S pts of 26.3, 21.4, and 80.6 mo (log rank p

< 0.0001). Median OS for PCR (83.2 mo) was superior to N-PCR (15.1

mo), p < 0.0001. CRT pts and N-PCR had no difference in OS (pZ 0.79).

On multivariate analysis (MVA) the difference between CRT and CRT + S

remained significant (HR Z 0.50, p Z 0.0049) after adjusting for his-

tology, stage, age, and gender. However, stratification of CRT + S pts by

nodal response showed no difference between CRT and N-PCR (HR Z0.81 favoring CRT, p Z 0.52). The PFS for WC, CRT, CRT + S, PCR, and

N-PCR pts were 9.9, 9.1, 22.7, 49.2, and 7.1 mo, respectively. On MVA,

the PFS for PCR pts was significantly better vs CRT (p < 0.0001), but

there was no difference between CRT and N-PCR (p Z 0.26). The benefit

in DMFS was limited to PCR vs CRT (median 62.3 mo vs 15.6 mo,

adjusted HRZ 0.244, p < 0.0001), while the adjusted HR favored CRT vs

N-PCR (HR Z 0.63, p Z 0.1151). There was a trend toward decreased

LRR for CRT + S vs CRT (Gray’s p Z 0.065), and no difference in LRR

between CRT and N-PCR (p Z 0.34).

Conclusions: In agreement with previous studies, pts with PCR experi-

enced markedly superior survival outcomes. However, pts who did not

achieve nodal clearance fared no better than the CRT cohort, emphasizing

the importance of preoperative nodal evaluation. Accurate assessment of

nodal status prior to post-induction surgery may provide an opportunity to

guide treatment decisions.

Author Disclosure: G. Hermann: None. E. Ziel: None. P. Bonomi: None.

M. Liptay: None. W. Warren: None. G. Chmielewski: None. M. Fidler:

None. M. Batus: None. D.J. Sher: None.

1137Phase 1 Dose Escalation Study of Accelerated Fractionation andConcurrent Chemotherapy Using Intensity Modulated RadiationTherapy for Locally Advanced Lung CancerC.R. Kelsey,1 L.B. Marks,2 S. Das,1 F. Dunphy,1 N. Ready,1 J. Crawford,1

and D. Yoo1; 1Duke University, Durham, NC, 2University of North

Carolina, Chapel Hill, NC

Purpose/Objective(s): Local failure occurs in a majority of patients with

locally-advanced lung cancer treated with radiation therapy (RT). Both

accelerated RT fractionation and concurrent chemotherapy (ChT) improve

local control and survival. Incorporating both strategies has generally led

to excessive toxicity, particularly high-grade esophagitis. In this prospec-

tive study, the maximum tolerated dose (MTD) of RT given in an accel-

erated fashion with concurrent ChT was investigated. Intensity modulated

radiation therapy (IMRT) was used to reduce the risk of esophagitis, the

primary dose-limiting toxicity (DLT) with both accelerated RT and con-

current ChT.

Materials/Methods: Patients with locally-advanced lung cancer (NSCLC

and SCLC) with ECOG PS 0-1, weight loss < 10%, and adequate he-

matologic/renal function were treated with concurrent cisplatin (50 mg/m2

days 1, 8, 29, 36) and etoposide (50 mg/m2 days 1-5 and 29-33). RT

International Journal of Radiation Oncol � Biology � PhysicsS214

treatment planning utilized 4D CT imaging with respiratory motion

management. RT was 2 Gy qd, 6 fractions/week (bid on Fridays with 6 h

interval). IMRT with daily image guidance was used to facilitate esopha-

geal avoidance with strict pulmonary constraints. The primary tumor + 5

mm and involved lymph nodes + 3 mm expansions comprised the CTV.

The PTV consisted of the CTV + a 3 mm expansion. Elective nodal

irradiation (ENI) was optional. The dose was escalated from 58 to 74 Gy in

4 Gy increments in a standard 3 + 3 trial design. DLTwas defined as acute

grade 3-5 non-hematologic toxicity (excluding outpatient IV fluid

requirements).

Results: Twenty-one patients were enrolled, filling all dose cohorts, all

completing RT and ChT as prescribed. Median age was 60 years (range

49-74 years), men Z 10 and women Z 11; NSCLC Z 18; SCLC Z 3.

ENI in 10/21 (44 Gy). Median (range) dosimetric parameters: Lung V5 Z43% (18-70), V20 Z 24% (5-39); Esophagus V20 Z 37% (21-65),

V60 Z 5% (0-41); and Heart mean dose Z 5 Gy (1-30). DLT occurred in

1 patient at 58 Gy (grade 3 esophagitis requiring hospitalization) and

1 patient at 70 Gy (grade 5 esophageal fistula). The first patient had a 12

cm tumor close to the esophagus and the second had a 10 cm tumor

abutting the esophagus. Three additional patients were enrolled at both

dose cohorts without further DLT. Esophageal toxicity (CTCAE, version

4.0) was grade 0, 1, 2, 3, 4, and 5 in 6, 3, 9, 2, 0, and 1 patient,

respectively. One patient with grade 3 esophagitis required transient IVFs,

recovered, not scored as DLT. There was one case of late grade 3 pneu-

monitis that was self-limited.

Conclusions: Dose escalation to 74 Gy using accelerated RT (6 fractions/

week) with concurrent ChT was achieved. This strategy appears to facil-

itate the delivery of accelerated RT concurrently with ChT, sparing severe

acute esophageal reactions, and should improve outcomes for patients with

lung cancer. High-grade esophageal complications appeared to be associ-

ated with large tumors adjacent to the esophagus.

Author Disclosure: C.R. Kelsey: E. Research Grant; Varian Medical

Systems. L.B. Marks: None. S. Das: None. F. Dunphy: None. N. Ready:

None. J. Crawford: None. D. Yoo: None.

1138Conformal Fields in Postoperative Radiation Therapy for NSCLC AreNot Associated With High Rates of Regional Nodal RecurrenceB. Farnia, S. Lin, C. Tang, P. Allen, Z. Liao, J. Chang, J. Welsh,

R. Komaki, R. Mehran, and D. Gomez; The University of Texas MD

Anderson Cancer Center, Houston, TX

Purpose/Objective(s): There exists a paucity of data on the effect of field

size on locoregional recurrence (LRR) rates in patients treated with

postoperative radiation therapy (PORT) for non-small cell lung cancer

(NSCLC). We examined outcomes following PORT for locally advanced

NSCLC at our institution and assessed nodal patterns of failure in relation

to field design.

Materials/Methods: We assessed 241 consecutive patients treated with

PORT at our institution between July 1998 and April 2010. All patients

received surgical resection with wedge resection (n Z 173, 71.8%),

lobectomy (n Z 36, 14.9%), or pneumonectomy (n Z 32, 13.3%). The

predominant T and N-stage was T2 (n Z 111, 46.1%) and pN2 (n Z165, 68.5%). PORT was delivered to a median dose of 50.4 Gy in 28

fractions, utilizing 2D (AP/PA, then off-cord obliques) (n Z 81, 33.6%),

3D conformal therapy (n Z 84, 34.8%), intensity modulated radiation

therapy (n Z 55, 22.8%), and proton beam therapy (n Z 7, 2.9%).

Radiation fields included a whole mediastinum (WM) field with 2D

techniques, transitioning to inclusion of only high-risk (HR) nodal re-

gions (involved or involved + adjacent regions) in select patients after

2004 with the advent of conformal techniques. Patients were defined as

having LRR if they had failure in the same lobe or mediastinum without

concurrent distant metastatic failure. Relationships between patient and

treatment characteristics and LRR free survival (LRRFS) were compared

via Log-rank tests with univariate hazard ratios (HRs) generated by Cox

regression analysis. Patients who experienced nodal failure were further

analyzed to determine the relation of the recurrence to the treatment

field.

Results: With a median time to LRR of 15.8 months (range, 3.7-84.4

months), 29 patients (12%) experienced LRR within (n Z 18, 7.5%)

and outside (n Z 11, 4.6%) of the PORT field. One, two, and five-year

rates of LRRFS were 95%, 90%, and 82%, respectively. Patients who

received wedge resection versus lobectomy experienced a higher LRR

(HR Z 3.60, 95% CI: 1.61-8.01, p Z 0.004). Nine patients with out-

of-field failures had nodal recurrence. Seven of these nine patients had

recurrence in supraclavicular lymph nodes, five treated with WM and

two with HR fields. Of the other two patients, one was treated with a

HR field and had recurrence in a 2R lymph node and the second was

treated with a WM field and had recurrence in multiple mediastinal

lymph nodes.

Conclusions: The majority of patients treated with PORT for NSCLC had

recurrence within the PORT field. Despite transitioning from a whole

mediastinum approach to high-risk nodal regions, out-of-field lymph node

failures were rare (4.6%) and primarily included the supraclavicular lymph

nodes. A conformal PORT field appears reasonable in the context of a

< 5% out-of-field regional nodal recurrence rate.

Author Disclosure: B. Farnia: None. S. Lin: None. C. Tang: None. P.

Allen: None. Z. Liao: None. J. Chang: None. J. Welsh: None. R.

Komaki: None. R. Mehran: None. D. Gomez: None.

1139The Effects of b-Adrenergic Antagonists on Radiation Therapy forLocally Advanced Lung CancersS.K. Cheng,1 K. Stephenson,2 A. Jain,1 D.P. Horowitz,1 S.X. Yan,2

T. Wang,1 K. Chao,1 and T.K. Hei1; 1New York Presbyterian Hospital

Columbia Campus, New York, NY, 2Columbia University, New York, NY

Purpose/Objective(s): Locally advanced non-small lung cancer (LA-

NSCLC) is highly resistant to conventional chemoradiation therapy, as

local disease failure occurs in up to 50% of the patients. We sought to

find out whether inhibiting the b-adrenergic pathway with beta-

blockers (BBs) resulted in different radiation sensitivities, and hy-

pothesized that the use of beta-blocker status is predictive of treatment

response and overall survival (OS) in patients treated with chemo-

radiation for LA-NSCLC.

Materials/Methods: To assess the efficacy of inhibiting the b-adrenergicpathway as a radiosensitizer in NSCLC, we analyzed with clonogenic

survival assay the human adenocarcinoma cell line (PC9) treated with and

without propranolol (a non-selective b-adrenergic receptor antagonist,

range 1 to 50 mM) and exposed to radiation (range 0 to 10 Gy). To examine

the association of beta-blockers (BBs) intake, treatment response, and

patient outcomes, we retrospectively evaluated 102 patients with stage III

NSCLC who received neoadjuvant platinum-based chemoradiation and

then surgery at a single institution between 2005 and 2012. Patient taking

BBs at the start of neoadjuvant therapy were compared with patients with

no BBs intake. Treatment response and patient oncologic outcomes be-

tween the groups were analyzed.

Results: Propranolol combined with radiation decreased clonogenic sur-

vivability of PC9 cells in vitro. A significant difference in the colony

forming rate was observed in combination with irradiation and propranolol

at 50 mM (p < 0.01) compared with irradiation alone. In our clinical

cohort, patients who used BBs (nZ 21) were compared with patients (nZ81) who did not. BBs use was associated with a significantly decreased

distant metastases rate (hazard ratio [HR], 0.55; 95% CI Z 0.31 to 0.93)

and there was a trend to improved primary lung tumor response to che-

moradiation via CT imaging (HR Z 0.68; 95% CI Z 0.45 to 1.12). A

trend to improved OS at 2 years was noted with BBs use (72%) compared

with no BBs use (53%, P Z 0.12).

Conclusions: Our results show that b-adrenergic pathway may regulate

multiple processes that contribute to tumor progression and treatment

response. In vitro, propranolol enhanced the sensitivity of lung cancer cells

to radiation. In the clinical cohort, BBs intake was associated with a

decreased distant metastases rate in patients with LA-NSCLC. Additional