accelerated hypofractionated radiation therapy plus chemotherapy for inoperable locally advanced...

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(50% drop, 75% drop, @ 3 cutoffs) was the same in the 2 dose groups. Median survival was 50 months for the entire cohort, with a 2- & 5- year survival of 88%, 65%. DE-RT pts have not yet achieved median survival. The 2-year DFS was 70% (37 mo median DFS). None of the factors including RT dose, T down staging, MNC, different cut off points for SUV drop were significant for outcomes on DFS, OS. At last follow-up, 17 pts (46%) were free of disease and 14 alive (38%). Conclusions: RT dose escalation resulted in improvement in MNC and correlated with the PET response in our series. Long-term follow-up and larger pt numbers are needed for the DE-RT pts to prove the concept. PET response can be utilized as predictor of outcomes in operable NSCLC pts. Author Disclosure: A. Turaka: None. S. Hasan: None. T. Li: None. R. Mehra: None. W.J. Scott: None. J.Q. Yu: None. 146 Accelerated Hypofractionated Radiation Therapy Plus Chemotherapy for Inoperable Locally Advanced Lung Cancer: Final Results of Long-term Follow-up Locally Advanced Non-Small Cell Lung Cancer E. Parisi, 1 G. Genestreti, 2 A. Romeo, 1 M. Romagnoli, 3 M. Burgio, 1 G. Ghigi, 1 D. Arpa, 1 A. Sarnelli, 1 A. Tesei, 1 and R. Polico 1 ; 1 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, Meldola, Italy, 2 Ospedale Bellaria, Bologna, Italy, 3 Ospedale Morgagni- Pierantoni, Forlı`, Italy Purpose/Objective(s): We previously reported the feasibility and acute toxicity of full-dose chemotherapy and accelerated hypo- fractionated radiation therapy in inoperable locally advanced non- small cell lung cancer (NSCLC). In this report, we present the long-term results of inoperable locally advanced NSCLC patients treated with high dose radiation therapy and full-dose chemotherapy (IRST protocol 162.01). The study was approved by our Medical and Scientific Committee. Materials/Methods: Treatment consisted of 2 cycles of induction chemotherapy (cisplatin/docetaxel), accelerated hypofractionated radia- tion therapy, and a further 2 cycles of consolidation chemotherapy. All patients had clinically documented stage IIIA (19%) or IIIB (81%) NSCLC confirmed by fine needle aspiration biopsy (FNAB), bronchos- copy, or transbronchial needle aspiration (TBNA). CT and CT/PET scans were used for initial staging and for restaging after completion of treatment. A bronchoscopy was performed before induction chemo- therapy and after radiation therapy. The dose prescribed was 30 Gy/5 daily fractions at the reference isodose (60%-70%) with an increasing dose inhomogeneity of up to 40 Gy inside the tumor, and 25 Gy/5 daily fractions at the reference isodose, with an increasing dose inhomogeneity of up to 37.5 Gy in the clinically involved lymph nodes. We analyzed overall survival, local progression-free survival, locoregional control, and long-term toxicity. Results: Of the 23 patients enrolled onto the study between January 2009 and January 2012, 19 were evaluable. The median follow up was 39 months (range 2-56). Median overall survival (OS) was 23 months (95% CI 9.6-55.5), median local progression-free survival was 19.8 months (95% CI 9.7-not reached), and median metastasis-free survival was 9.7 months (95% CI 5.8-46.0). At the end of the study, 47% of patients were downstaged and 1 patient underwent surgery. No late grade 3/4 toxicity from radiation therapy was observed. Accrual was closed before the target sample size was met. Conclusions: Our results show that accelerated hypofractionated radiation therapy and full dose chemotherapy was possible without high-grade toxicity. In particular, a week-long treatment using accelerated hypo- fractionated radiation therapy in inoperable locally advanced lung cancer was reasonably well tolerated. We also demonstrated that accelerated hypofractionation for central primary tumor volumes (T3, T4) and medi- astinal lymph node stations can be administered without causing severe acute and late side-effects. No grade 3/4 for late toxicity was recorded. The median OS of 23 months for IIIB lung cancer compares favorably with literature data. Author Disclosure: E. Parisi: None. G. Genestreti: None. A. Romeo: None. M. Romagnoli: None. M. Burgio: None. G. Ghigi: None. D. Arpa: None. A. Sarnelli: None. A. Tesei: None. R. Polico: None. 147 WITHDRAWN 148 WITHDRAWN 149 Prognostic Biomarkers in Non-Small Cell Lung Cancer Patients Treated With Radiation Therapy Locally Advanced Non-Small Cell Lung Cancer S. Kumar, 1 B. Movsas, 2 S.L. Brown, 2 M. Simoff, 2 C.H. Stone, 2 K.A. Jenrow, 2 K. Lapanowski, 2 M. Ajlouni, 2 I.J. Chetty, 2 A. Movsas, 3 M. Lu, 2 A. Sitarik, 2 L. Lamerato, 2 M.R. Jones, 4 Z. Hammoud, 2 N. Peshkin, 2 K. Roszka, 2 and R. Parry 5 ; 1 Henry Ford Health System, Detroit, MI, 2 Henry Ford Health System, Detroit, MI, 3 University of Michigan, Ann Arbor, MI, 4 Oakland University, Rochester, MI, 5 Varian Medical Systems, San Francisco, CA Purpose/Objective(s): To determine specific tumor biomarkers predicting radiation therapy response in non-small cell lung cancer (NSCLC) patients. Materials/Methods: Tumors from NSCLC patients (nZ133) treated with curative radiation therapy alone or combined with chemotherapy (initially presenting with stage I, II, or III disease comprising 21%, 15%, and 64% of patients, respectively) were examined for the following 8 biomarkers: ALDH1A1, CD68, Hyaluronic acid, Beta-Catenin, CD44, MFG-E8, Matrix metalloproteinase-9 (MMP-9) and Vimentin, as a control. The markers were selected based on their correlation with TGF-beta expression and/or association with tumor aggressiveness, radioresistance, and poor prognosis in several tumor indications. Survival time was calculated using a Cox proportional hazards model. Univariate analyses followed by multivariate models were examined to determine biomarkers and other factors predictive of survival. A logistic regression model was used to analyze factors predicting for local control. Results: High CD68 expression was associated with an increased risk of death (PZ.008), while there was a trend towards a decreased risk of death associated with high MMP-9 expression (PZ.05). Squamous cell carcinoma histology was associated with higherodds of local failure compared to adenocarcinoma [Odds ratio, [OR] Z 4.39, 95% confidence interval [CI] Z 0.96-19.98). Expression of CD44 was associated with significantly increased odds of local tumor failure (OR Z 1.44, 95% CI Z 1.08-1.92), while MFG-E8 was asso- ciated with decreased odds of local tumor failure (OR Z 0.77, 95% CI Z 0.62- 0.97). Combined, CD44, MFG-E8, and tumor type were predictive of local control with an area under the curve value of 0.74 (1.00 being a perfect pre- dictor). The median survival time among all patients was 1.5 years. The only patient characteristic on univariate model analyses exhibiting a difference in survival was race, with African-Americans (AA) having a 1.5 times greater risk of death than non-AA (PZ.044), while the overall effect of race on survival was not significant (PZ.76). The overall main effect of median household income remained insignificant (PZ.099), as in the univariate analysis. How- ever, after checking for effect modification, the median household income significantly modified the effect of race on survival (PZ.037), and that model fit was improved. AA were only at a significantly higher risk when median household income was between $30,000 and $50,000 (PZ.002). Conclusions: Among the NSCLC treated with radiation therapy, CD68 was predictive of increased risk of death, while MMP-9 decreased the risk of death. Racial disparities in survival were dependent on median house- hold income. High expression of CD44 and low expression of MFG-E8 were predictive of local tumor control. Author Disclosure: S. Kumar: None. B. Movsas: E. Research Grant; Varian Medical Systems. S.L. Brown: E. Research Grant; Varian Medical Volume 90 Number 5S Supplement 2014 Poster Presentations S25

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Page 1: Accelerated Hypofractionated Radiation Therapy Plus Chemotherapy for Inoperable Locally Advanced Lung Cancer: Final Results of Long-term Follow-up

Volume 90 � Number 5S � Supplement 2014 Poster Presentations S25

(50% drop, 75% drop, @ 3 cutoffs) was the same in the 2 dose groups.

Median survival was 50 months for the entire cohort, with a 2- & 5- year

survival of 88%, 65%. DE-RT pts have not yet achieved median survival.

The 2-year DFS was 70% (37 mo median DFS). None of the factors

including RT dose, T down staging, MNC, different cut off points for

SUV drop were significant for outcomes on DFS, OS. At last follow-up,

17 pts (46%) were free of disease and 14 alive (38%).

Conclusions: RT dose escalation resulted in improvement in MNC and

correlated with the PET response in our series. Long-term follow-up and

larger pt numbers are needed for the DE-RT pts to prove the concept.

PET response can be utilized as predictor of outcomes in operable

NSCLC pts.

Author Disclosure: A. Turaka: None. S. Hasan: None. T. Li: None. R.

Mehra: None. W.J. Scott: None. J.Q. Yu: None.

146Accelerated Hypofractionated Radiation Therapy PlusChemotherapy for Inoperable Locally Advanced Lung Cancer: FinalResults of Long-term Follow-upLocally Advanced Non-Small Cell Lung CancerE. Parisi,1 G. Genestreti,2 A. Romeo,1 M. Romagnoli,3 M. Burgio,1

G. Ghigi,1 D. Arpa,1 A. Sarnelli,1 A. Tesei,1 and R. Polico1; 1Istituto

Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS,

Meldola, Italy, 2Ospedale Bellaria, Bologna, Italy, 3Ospedale Morgagni-

Pierantoni, Forlı̀, Italy

Purpose/Objective(s): We previously reported the feasibility and

acute toxicity of full-dose chemotherapy and accelerated hypo-

fractionated radiation therapy in inoperable locally advanced non-

small cell lung cancer (NSCLC). In this report, we present the

long-term results of inoperable locally advanced NSCLC patients

treated with high dose radiation therapy and full-dose chemotherapy

(IRST protocol 162.01). The study was approved by our Medical and

Scientific Committee.

Materials/Methods: Treatment consisted of 2 cycles of induction

chemotherapy (cisplatin/docetaxel), accelerated hypofractionated radia-

tion therapy, and a further 2 cycles of consolidation chemotherapy. All

patients had clinically documented stage IIIA (19%) or IIIB (81%)

NSCLC confirmed by fine needle aspiration biopsy (FNAB), bronchos-

copy, or transbronchial needle aspiration (TBNA). CT and CT/PET scans

were used for initial staging and for restaging after completion of

treatment. A bronchoscopy was performed before induction chemo-

therapy and after radiation therapy. The dose prescribed was 30 Gy/5

daily fractions at the reference isodose (60%-70%) with an increasing

dose inhomogeneity of up to 40 Gy inside the tumor, and 25 Gy/5 daily

fractions at the reference isodose, with an increasing dose inhomogeneity

of up to 37.5 Gy in the clinically involved lymph nodes. We analyzed

overall survival, local progression-free survival, locoregional control, and

long-term toxicity.

Results: Of the 23 patients enrolled onto the study between January 2009

and January 2012, 19 were evaluable. The median follow up was 39

months (range 2-56). Median overall survival (OS) was 23 months (95%

CI 9.6-55.5), median local progression-free survival was 19.8 months

(95% CI 9.7-not reached), and median metastasis-free survival was 9.7

months (95% CI 5.8-46.0). At the end of the study, 47% of patients were

downstaged and 1 patient underwent surgery. No late grade 3/4 toxicity

from radiation therapy was observed. Accrual was closed before the target

sample size was met.

Conclusions: Our results show that accelerated hypofractionated radiation

therapy and full dose chemotherapy was possible without high-grade

toxicity. In particular, a week-long treatment using accelerated hypo-

fractionated radiation therapy in inoperable locally advanced lung cancer

was reasonably well tolerated. We also demonstrated that accelerated

hypofractionation for central primary tumor volumes (T3, T4) and medi-

astinal lymph node stations can be administered without causing severe

acute and late side-effects. No grade 3/4 for late toxicity was recorded. The

median OS of 23 months for IIIB lung cancer compares favorably with

literature data.

Author Disclosure: E. Parisi: None. G. Genestreti: None. A. Romeo:

None. M. Romagnoli: None. M. Burgio: None. G. Ghigi: None. D.

Arpa: None. A. Sarnelli: None. A. Tesei: None. R. Polico: None.

147WITHDRAWN

148WITHDRAWN

149Prognostic Biomarkers in Non-Small Cell Lung Cancer PatientsTreated With Radiation TherapyLocally Advanced Non-Small Cell Lung Cancer

S. Kumar,1 B. Movsas,2 S.L. Brown,2 M. Simoff,2 C.H. Stone,2

K.A. Jenrow,2 K. Lapanowski,2 M. Ajlouni,2 I.J. Chetty,2 A. Movsas,3

M. Lu,2 A. Sitarik,2 L. Lamerato,2 M.R. Jones,4 Z. Hammoud,2

N. Peshkin,2 K. Roszka,2 and R. Parry5; 1Henry Ford Health System,

Detroit, MI, 2Henry Ford Health System, Detroit, MI, 3University of

Michigan, Ann Arbor, MI, 4Oakland University, Rochester, MI, 5Varian

Medical Systems, San Francisco, CA

Purpose/Objective(s): To determine specific tumor biomarkers predicting

radiation therapy response in non-small cell lung cancer (NSCLC)

patients.

Materials/Methods: Tumors from NSCLC patients (nZ133) treated with

curative radiation therapy alone or combined with chemotherapy (initially

presenting with stage I, II, or III disease comprising 21%, 15%, and 64% of

patients, respectively) were examined for the following 8 biomarkers:

ALDH1A1, CD68, Hyaluronic acid, Beta-Catenin, CD44, MFG-E8, Matrix

metalloproteinase-9 (MMP-9) and Vimentin, as a control. The markers were

selected based on their correlationwith TGF-beta expression and/or association

with tumor aggressiveness, radioresistance, and poor prognosis in several tumor

indications. Survival time was calculated using a Cox proportional hazards

model. Univariate analyses followed by multivariate models were examined to

determine biomarkers and other factors predictive of survival. A logistic

regression model was used to analyze factors predicting for local control.

Results: HighCD68 expressionwas associatedwith an increased risk of death(PZ.008), while therewas a trend towards a decreased risk of death associated

with high MMP-9 expression (PZ.05). Squamous cell carcinoma histology

was associated with higherodds of local failure compared to adenocarcinoma

[Odds ratio, [OR] Z 4.39, 95% confidence interval [CI] Z 0.96-19.98).

Expression of CD44 was associated with significantly increased odds of local

tumor failure (OR Z 1.44, 95% CI Z 1.08-1.92), while MFG-E8 was asso-

ciatedwith decreased odds of local tumor failure (ORZ 0.77, 95%CIZ 0.62-

0.97). Combined, CD44, MFG-E8, and tumor type were predictive of local

control with an area under the curve value of 0.74 (1.00 being a perfect pre-

dictor). The median survival time among all patients was 1.5 years. The only

patient characteristic on univariate model analyses exhibiting a difference in

survivalwas race,withAfrican-Americans (AA) having a 1.5 times greater risk

of death than non-AA (PZ.044), while the overall effect of race on survival

was not significant (PZ.76). The overall main effect of median household

income remained insignificant (PZ.099), as in the univariate analysis. How-

ever, after checking for effect modification, the median household income

significantly modified the effect of race on survival (PZ.037), and that model

fit was improved. AA were only at a significantly higher risk when median

household income was between $30,000 and $50,000 (PZ.002).

Conclusions: Among the NSCLC treated with radiation therapy, CD68

was predictive of increased risk of death, while MMP-9 decreased the risk

of death. Racial disparities in survival were dependent on median house-

hold income. High expression of CD44 and low expression of MFG-E8

were predictive of local tumor control.

Author Disclosure: S. Kumar: None. B. Movsas: E. Research Grant;

Varian Medical Systems. S.L. Brown: E. Research Grant; Varian Medical