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

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  • 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 andcorrelated 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, Forl, Italy

    Purpose/Objective(s): We previously reported the feasibility andacute 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 inductionchemotherapy (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 2009and 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 radiationtherapy 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. Themedian 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 predictingradiation therapy response in non-small cell lung cancer (NSCLC)

    patients.

    Materials/Methods: Tumors from NSCLC patients (nZ133) treated withcurative 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 associatedwith high MMP-9 expression (PZ.05). Squamous cell carcinoma histologywas 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 survivalwas not significant (PZ.76). The overall main effect of median householdincome 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 modelfit 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, CD68was 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

    Outline placeholderConclusions

    Accelerated Hypofractionated Radiation Therapy Plus Chemotherapy for Inoperable Locally Advanced Lung Cancer: Final Results ...Purpose/Objective(s)Materials/MethodsResultsConclusions

    WITHDRAWNWITHDRAWNPrognostic Biomarkers in Non-Small Cell Lung Cancer Patients Treated With Radiation TherapyPurpose/Objective(s)Materials/MethodsResultsConclusions

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