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Andrew Michael Hudson



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    P2.01 - Advanced NSCLC (ID 159)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.01-08 - Clinical Trial in Progress: CONCORDE - A Phase 1B Study of Novel Agents in Combination with Conventional Radiotherapy in NSCLC (ID 600)

      10:15 - 18:15  |  Presenting Author(s): Andrew Michael Hudson

      • Abstract

      Background

      The majority of patients with locally advanced non-small cell lung cancer (NSCLC) treated with curative intent receive radiotherapy (RT) as part of their treatment. Despite considerable technological advances in RT delivery, the survival of these patients has barely changed over the last 60 years. A major factor in this failure to improve outcomes is the relative radioresistance of NSCLC. Attempts to overcome radioresistance by escalating RT doses have demonstrated inferior outcome likely secondary to normal tissue toxicity. Therefore an alternate approach is to exploit genetic dependencies in the DNA damage response of NSCLC, using biological inhibitors to selectively radiosensitise tumours whilst sparing normal tissues. The CONCORDE study is a multi-arm phase 1B platform study to investigate the combination of radical RT with DNA damage response inhibitors (DDR-i) targeting five different proteins: PARP, ATR, WEE1, ATM, DNA-PK.

      Method

      CONCORDE is a hypothesis-driven combination study of novel therapeutics and RT using an innovative adaptive early-phase trial design. The study will address two main research questions:

      - What are the recommended phase 2 doses (RP2D) of individual DDR-i in combination with curative RT in patients with stage IIB/III NSCLC?

      - What are the safety profiles of individual DDR-i combined with curative RT in this population?

      Key inclusion criteria are stage IIB and III NSCLC planned to receive curative intent RT doses (+/- neoadjuvant chemotherapy) and PS 0-1. Participants will be randomised on a 3:1 basis between DDR-i with RT or RT alone. Patients receiving RT alone will be pooled across the arms to provide contemporary data on toxicity. All patients will receive external beam RT with a planned dose of 60 Gy in 30 fractions.

      The study will use a Bayesian adaptive model-based approach to dose-escalation, with separate Time-To-Event Continual Reassessment Method (TiTE-CRM) models in each experimental arm. The primary endpoints are dose-limiting toxicities occurring within 12 months of the start of radiotherapy. Secondary endpoints include safety and toxicity (acute and late toxicity up to 2 years including using patient reported outcome (PRO) measures), treatment compliance, and best overall response (using RECIST 1.1, progression-free, and overall survival).

      Correlative studies will be carried out to identify biomarkers of toxicity and response. We have secured high-level agreement from leading pharmaceutical partners to invest in 5 treatment arms and funding approval from Cancer Research UK is pending. The first participant is estimated to commence treatment in late 2019

      Result

      Section not applicable

      Conclusion

      Section not applicable

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    P2.08 - Oligometastatic NSCLC (ID 172)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Oligometastatic NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.08-02 - Outcomes Following Stereotactic Radiosurgery for Syncronous Brain Metastases in Non-Small Cell Lung Cancer (ID 426)

      10:15 - 18:15  |  Author(s): Andrew Michael Hudson

      • Abstract
      • Slides

      Background

      Approximately 10% of non-small cell lung cancer (NSCLC) patients have brain metastases at presentation. The use of stereotactic radiosurgery (SRS) has enabled a proportion of patients with oligometastatic brain disease to be offered a radical treatment in conjunction with SRS. We evaluated the outcomes for patients presenting with synchronous brain metastases who received SRS to determine if radical treatment improves survival.

      Method

      164 patients with NSCLC received SRS for brain metastases between January 2012 and December 2017. This analysis focused on 71 patients who presented synchronously with brain metastases. Electronic patient records were accessed in March 2019 to determine initial extracranial disease treatment and date of death or last follow up.

      Result

      30 patients received radical treatment (18 radiotherapy alone, 11 chemo-radiotherapy and one surgery) and 24 received palliative treatment (17 chemotherapy, four radiotherapy and three tyrosine kinase inhibitor). 17 patients received no treatment following SRS, either due to death, deterioration in performance status or patient choice. Baseline demographics are presented in table 1.

      table 1.jpg

      Median overall survival for the radical, palliative and no treatment groups were; 7.9 (95% CI 5.5-14.0), 9.4 (6.6-14.4) and 1.4 (1.0-2.9) months, respectively. There was no significant difference in survival between the radical and palliative groups (p=0.43). Kaplan-Meier survival estimates at 12 and 24 months were 30.0% (95% CI 17.4- 51.8%) and 10.0% (3.4-29.3%) for the radical and 33.3% (18.9- 58.7%) and 13.0% (4.1-41.4%) in the palliative group, respectively.

      Conclusion

      Our results did not demonstrate the benefit for radical treatment, as expected based on published data. Potential reasons for this result include a lack of tools to select patients for radical treatment. Prospective studies are needed to identify the optimal treatment for extracranial disease in this patient group.

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    P2.17 - Treatment of Early Stage/Localized Disease (ID 189)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.17-02 - Survival in Performance Status 3 Non-Small Cell Lung Cancer Patients Receiving Radical Radiotherapy (ID 291)

      10:15 - 18:15  |  Author(s): Andrew Michael Hudson

      • Abstract
      • Slides

      Background

      International guidelines currently recommend radical radiotherapy for non-small cell lung cancer (NSCLC) patients with ECOG performance status (PS)0-2. Despite a paucity of evidence for treating poorer PS patients, modern advances have allowed patients with PS3 to be offered radical radiotherapy.

      Method

      PS0-3 NSCLC patients receiving radical radiotherapy at The Christie Hospital, UK between August 2016-October 2017 were retrospectively identified from hospital electronic patient records. Survival was calculated from date of first oncology review to November 2018. Baseline and treatment characteristics for PS3 patients were recorded including adult comorbidity evaluation (ACE)-27 score, pulmonary function, radiation dose volume parameters and radiotherapy regimen (i.e stereotactic ablative radiotherapy (SABR) vs standard radiotherapy (50-55Gy/20 fractions)).

      Result

      504 patients were identified: 440(87%) PS0-2 and 64(13%) PS3. Six PS3 patients withdrew themselves; four before treatment and two after one fraction. Of 58/64(91%) PS3 patients completing radiotherapy, 43(74%), 4(7%), 10(17%) and 1(2%) were Stage I, II, III and IV at diagnosis, respectively. ACE-27 score was 0, 1, 2 and 3 in 3(5%), 8(14%), 16(28%) and 31(53%) patients, respectively. 31(53%) received SABR and 27(47%) standard radiotherapy. On intention-to-treat analysis, there was no significant difference in survival over 18 months in PS3 patients compared to PS0-2; p=0.858 (Fig.1). There was no significant difference in survival among PS3 patients completing radiotherapy when stratifying by stage(I vs II vs III) (p=0.343), ACE-27 score(1 vs 2 vs 3)(p=0.266), or radiotherapy regimen(p=0.655). Lung function tests(FEV1, FVC) and radiotherapy dose volume parameters(PTV, V5, V10,V20) failed to predict survival of PS3 patients at 6, 12 and 18 months.

      nsclc rb.png

      Conclusion

      This study demonstrates that PS3 patients receiving radical radiotherapy had a similar 18-month survival compared to PS0-2 patients and baseline and treatment characteristics did not predict overall survival in PS3 patients. This suggests more PS3 patients could be considered for radical radiotherapy and further studies with larger cohorts are recommended.

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