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M.E. Daly



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    MINI 07 - ChemoRT and Translational Science (ID 110)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Treatment of Locoregional Disease – NSCLC
    • Presentations: 1
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      MINI07.13 - Clinical Impact of Frequent Surveillance Imaging in the First Year following Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer (ID 2538)

      16:45 - 18:15  |  Author(s): M.E. Daly

      • Abstract
      • Presentation
      • Slides

      Background:
      Uncertainty exists regarding the optimal surveillance strategy following definitive chemoradiation (CRT) for locally advanced non-small cell lung cancer (LA-NSCLC) with regards to both frequency and modality. We sought to determine the efficacy of frequent (q2-4 month) post-treatment imaging in detecting asymptomatic recurrent disease and document the clinical impact of frequent surveillance imaging.

      Methods:
      The records of all patients treated with CRT for stage IIIA/IIIB NSCLC between August 1999 and April 2014 at our institution were reviewed. Patients were included if they underwent frequent (Q2-4 month) chest computed tomography (CT) or positron emission tomography (PET/CT) for routine surveillance following CRT for at least one year following CRT or until disease progression or death. Radiographic findings and clinical interventions from the first year following CRT were identified.

      Results:
      We identified 145 patients with LA-NSCLC treated with CRT, 65 of whom underwent Q2-4 month surveillance imaging for at least one year or until progression or death. Median age was 63.6 years (range, 41.0-86.9 years). Forty-nine (75.4%) also underwent an initial baseline CT within the first 6 weeks following CRT. An asymptomatic recurrence was detected by surveillance imaging within the first year in 40 (61.5%) patients, 31 (77.5%) by CT and 9 (22.5%) by PET/CT. Among these patients, 21 (52.5%) initiated palliative systemic therapy. Three (7.5%) underwent attempted definitive therapy for isolated disease, including one patient treated with definitive lobectomy for what was found to be a histologically distinct new primary early stage NSCLC, and two patients treated with stereotactic ablative radiotherapy for isolated recurrences, both of whom subsequently developed metastatic disease. Urgent palliative local therapies (radiotherapy and bronchoscopy) were performed in 2 patients for impending neurologic and airway compromise, respectively. Ten patients (25%) with recurrences detected on surveillance imaging were not candidates for or declined additional cancer-directed therapy. Seven patients (10.8%) developed a symptomatic recurrence detected between planned scans. Five patients (7.7%) underwent additional diagnostic procedures for false-positive surveillance imaging findings.

      Conclusion:
      Frequent surveillance imaging within the first year following CRT for LA-NSCLC detected asymptomatic recurrences in a high proportion of patients in our population. However, definitive interventions were attempted in less than 5%, and were successful in only one patient. The predominant potential benefit of frequent radiographic surveillance appears to be the expedient initiation of palliative systemic therapy. Evidence-based algorithms for follow-up imaging among this population are needed, and should account for patient-specific factors including expected tolerance of, benefit from, and willingness to undergo systemic therapies.

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    P1.02 - Poster Session/ Treatment of Localized Disease – NSCLC (ID 209)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Treatment of Localized Disease - NSCLC
    • Presentations: 1
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      P1.02-036 - Peripheral Blood Immunophenotype Changes Following Thoracic Stereotactic Ablative Radiotherapy (ID 2282)

      09:30 - 17:00  |  Author(s): M.E. Daly

      • Abstract
      • Slides

      Background:
      Stereotactic ablative radiotherapy (SAR) is a standard therapy for early stage, medically inoperable non-small cell lung cancer (NSCLC) and select metastatic tumors. Strategies combining SAR and immune checkpoint inhibitors are of great interest in potentially augmenting anti-tumor immune response, and prospective trials evaluating SAR/immunotherapy combinations are underway. However, the systemic immune response profile following SAR is poorly defined. Better understanding of the systemic immune response following SAR should allow optimization of SAR/immunotherapy protocols. We performed pre and 1 week post-SAR immune profiling on patients undergoing lung SAR, focusing on central memory T-cells which have been implicated as important mediators of systemic anti-tumor immune responses.

      Methods:
      Patients are actively accruing to an IRB approved protocol examining systemic immunophenotype changes following SAR for early stage (T1-2N0) NSCLC or metastatic lesions to the lung. Patients underwent collection of 30 cc blood by venipuncture immediately prior to and at 1 week post-SAR to a median dose of 50 Gy (range: 50-54 Gy) over 5 fractions (range: 3-5 fractions). Immunophenotyping of peripheral blood mononuclear cells (pbmc’s) was performed using flow cytometric analysis. Central Memory T-cells were defined as CD62L+ and CD45RA- subsets of CD4+ or CD8+ T-cells. Changes pre-treatment to post-treatment were compared across the cohort using a paired T-test.

      Results:
      To date eleven NSCLC patients have accrued, and evaluable pre- and post-SAR specimens are available for six, all with early stage NSCLC (T1=4, T2=2, synchronous primaries =1). At one week post-SAR increases in systemic central memory CD4+ T-cells were observed in 4/6 patients and increases in systemic central memory CD8+ T-cells were observed in 3/6 patients with substantial (up to 10-fold) increases observed in some patients. Across the cohort the percent of circulating memory CD4+ T-cells increased from 1.9% pre-SAR to 3.1% post-SAR (p=0.06, Figure 1) and the percent of circulating memory CD8+ T-cells increased from 0.3% pre-SAR to 0.5% post-SAR (p=0.34, Figure 1).

      Conclusion:
      Our preliminary data in a limited patient cohort suggest lung SAR may induce systemic upregulation of circulating central memory T-cells which may be important mediators of the anti-tumor immune response. As more patients accrue, additional post-treatment time points are evaluated, and further analyses including cytokine/chemokine signatures are performed, we aim to better define systemic immunophenotype changes induced by lung SAR, assess how these changes relate to treatment toxicity and efficacy, and whether they can predict which patients will most likely benefit from the addition of immunotherapy to SAR. Figure 1



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