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Gerard G Hanna



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    IBS19 - Novel Approaches in Radiation Oncology for Small Cell and Neuroendocrine Cancers (Ticketed Session) (ID 50)

    • Event: WCLC 2019
    • Type: Interactive Breakfast Session
    • Track: Small Cell Lung Cancer/NET
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 07:00 - 08:00, Seoul (2007)
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      IBS19.02 - Novel Radiotherapy Approaches in Small Cell Lung Carcinoma – Has SABR and Radionuclide Therapy Got a Role to Play? (Now Available) (ID 3373)

      07:00 - 08:00  |  Presenting Author(s): Gerard G Hanna

      • Abstract
      • Presentation
      • Slides

      Abstract

      Novel Radiotherapy Approaches in Small Cell Lung Carcinoma – has SABR and Radionuclide therapy got a role to play?

      Thoracic radiotherapy has been shown in to increase overall survival when added to systemic therapy in patients with small cell lung carcinoma (SCLC) and M0 stage. The dose, fractionation, treatment time and timing issues have not been fully resolved. A recent study did not show the superiority of 66Gy in 33 daily fractions over 6.5 weeks over twice-daily radiotherapy to a dose of 45 Gy in 30 fractions over 3 weeks twice daily [1]. For stage I non-small cell lung carcinoma (NSCLC), stereotactic ablative body radiotherapy (SABR) has been clearly shown to be superior to conventional fractionation [2]. Given the clear benefit seen in early stage NSCLC, it is postulated that SABR may have a role to play in early stage SCLC. A recent multi-institutional cohort study has reported favourable outcomes in this setting [3]. However, randomised data of equivalence or indeed superiority are lacking. Furthermore, questions remain as the timing and role of systemic therapy and prophylactic cranial irradiation when SABR is used in this setting.

      In advanced SCLC, many tumors display neuroendocrine clinical and cytological features and many SCLC tumors express somatostatin receptor and this can be imaged using radiolabeled somatostatin analogs such as 68Ga-DOTATATE [4]. Given the uptake by some SCLC tumors of 68Ga-DOTATATE, higher doses of the tracer have been used in an attempt to provide radiolabelled radiotherapy treatment in metastatic disease in what has been described as peptide receptor radionuclide therapy (PRRT) [5]. This molecularly target radiotherapy is a potentially exciting therapeutic approach, but the ideal positioning of such therapy in tumors which are suitable for treatment with PRRT and the safety of PRRT with systemic therapy have yet to be determined.

      References:

      1. Faivre-Finn C, Snee M, Ashcroft L, et al. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial. Lancet Oncol. 2017;18(8):1116–1125. doi:10.1016/S1470-2045(17)30318-2

      2. Ball D, Mai GT, Vinod S, et al. Stereotactic ablative radiotherapy versus standard radiotherapy in stage 1 non-small cell lung cancer (TROG 09.02. CHISEL): a phase 3, open-label, randomised controlled trial. The Lancet. 2019; 20: 494-503

      3. Verma V, Simone CB, 2nd, Allen PK, et al. Multi-Institutional Experience of Stereotactic Ablative Radiation Therapy for Stage I Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys 2017;97:362-71

      4. Sollini M, Farioli D, Froio A, et al. Brief Report on the Use of Radiolabeled Somatostatin Analogs for the Diagnosis and Treatment of Metastatic Small-Cell Lung Cancer Patients. J Thor Oncol 2013;8(8):1095-1101.

      5. Lapa C, Hänscheid H, Wild V, et al. Somatostatin receptor expression in small cell lung cancer as a prognostic marker and a target for peptide receptor radionuclide therapy. Oncotarget. 2016 Apr 12;7(15):20033-40.

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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  |  Author(s): Gerard G Hanna

      • 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