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Antonin Levy



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    MA08 - Pawing the Way to Improve Outcomes in Stage III NSCLC (ID 127)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 1
    • Now Available
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      MA08.02 - Durvalumab Impact in the Treatment Strategy of Stage III Non-Small Cell Lung Cancer (NSCLC): An EORTC Young Investigator Lung Cancer Group Survey (Now Available) (ID 608)

      15:15 - 16:45  |  Author(s): Antonin Levy

      • Abstract
      • Presentation
      • Slides

      Background

      Stage III NSCLC represents a very heterogeneous population with extremely different treatment modalities including surgery, chemotherapy (CT) and radiotherapy (RT), mostly in combination. The results of the PACIFIC trial have now been reported in full including an overall survival (OS) benefit with durvalumab in addition to concomitant CT-RT. An electronic European survey was circulated to evaluate the impact of durvalumab in the staging and treatment strategy of stage III disease.

      Method

      A Young Investigator EORTC Lung Cancer Group survey containing 31 questions, was distributed between 31/01/18 and 31/03/19 to EORTC LCG and several European thoracic oncology societies’ members

      Result

      206 responses were analyzed (radiation oncologist: 50% [n=103], pulmonologist: 26.7% [n=55], medical oncologist: 22.3% [n=46]; 81.5% with >5 years experience in treating NSCLC). Italy (27.7%, n=57), Netherlands (22.8%, n=47), France (13.6%, n=28), and Spain (11.6%, n=24) contributed most. 83.5% (n=172) confirmed that they had access to durvalumab at the time of the survey. 97.6% (n=201) report that treatment decision is made by a multidisciplinary board. Regarding staging, 76.7% (n=158) support the need of a mediastinal pathological staging in case of suspect lymph-nodes, with a preference for EBUS/EUS (61.2%, n=126). 81.6% (n=168) treated more than half of patients with a concomitant CT-RT with the 1st cycle of chemotherapy in 39.7% (n=81). 95.1% consider durvalumab as practice changing, especially given the OS results (77.9%, n=152/195). 30% (n=119/395) will give patients concomitant CT-RT if PD-L1 >1%, and in borderline resectable cases 17.7% (n=70/395) will propose concomitant CT-RT instead of surgery. Durvalumab administration will be given regardless of PDL1 status in 13.1% (n=27) and 28.6% (n=59) would consider the possibility of a rebiopsy after CT-RT in case of negative PD-L1. 38.8% (n=80) foresee some problems with PD-L1 testing in this population due to availability of cytologic or small histologic samples. About 53.8% (n=105/195) normally will start durvalumab within 6 weeks after CT-RT and 48.5% (n=100) would also use durvalumab after sequential CT-RT

      Conclusion

      Durvalumab results are changing the treatment approach to stage III unresectable (and maybe resectable) NSCLC and planned strict adherence to the patient population as recruited to the PACIFIC study, was not demonstrated. This survey was released after the EMA approval of durvalumab and PD-L1 status seems to play a role in the treatment strategies, but surprisingly almost half of the clinicians will use durvalumab after sequential CT-RT without safety or efficacy data.

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    MS07 - Controversies with Stereotactic Radiation in Early Stage Lung Cancer (ID 70)

    • Event: WCLC 2019
    • Type: Mini Symposium
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Now Available
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      MS07.06 - Hot Topics in SBRT - Biopsy, Central Lesions, Radiologic Evaluation (Now Available) (ID 3479)

      14:00 - 15:30  |  Author(s): Antonin Levy

      • Abstract
      • Presentation
      • Slides

      Abstract

      Stereotactic body radiotherapy (SBRT) has taken a growing place among treatment strategies in lung cancer in the past ten years because of its reported good results and favourable risk-benefit ratio especially in high-risk patients. This treatment modality allows delivering precisely a very high dose of radiation therapy to a targetable lesion, using a small number of fractions (3 to 5 more frequently). It has become the standard of care in medically inoperable peripheral early stage non-small cell lung cancer (NSCLC) patients. It is also frequently used in metastatic patients to treat cranial as well as extra-cranial metastases. Recently small randomised studies evaluating SBRT in oligometastatic NSCLC have shown promising results. Its role is now well accepted however there are situations where SBRT is still a subject of controversy and may be regarded as a hot topic

      because of the lack of pre-treatment biopsy

      because of less favourable outcome in central lesions and higher risk of complications

      because of the difficulty of radiologic evaluation

      When a peripheral lung nodule is discovered, suspect of being lung cancer, attempt should be made to obtain a pathological diagnosis before any treatment is proposed. Percutaneous CT–guided transthoracic biopsy is the established investigation in the work-up of pulmonary nodules, but there is a risk of complications such as pneumothorax (20-40%). However in patients with poor lung function (severe COPD, emphysema..), tissue sampling can be particularly challenging especially when the nodule is beyond the reach of conventional bronchoscopy. These are typically the patients that may be considered for SBRT, possibly presenting a contra-indication to transthoracic biopsy. Criteria for definition of a nodule as lung cancer without biopsy confirmation have been proposed such as progressive growth on CT imaging or presence of a hypermetabolic lesion on PET scan, and multidisciplinary tumor board consensus on the clinical diagnosis of lung cancer; there should be at least a 85% risk of malignancy, based upon accepted criteria [Postmus; Louie, Reid].

      If stereotactic radiotherapy in peripheral early NSCLC is presently a standard of care in inoperable patients due to co-morbidities and age, its role is more controversial for centrally located tumors because of less favorable outcome and higher risk of complications. In the past years, there has been a need to better classify these patients differentiating ultra-central from central lesions. The RTOG 0813 phase I/II trial, evaluated dose escalation in 120 patients with centrally-located non-small lung cancer with a five-fraction schedule that ranged from 10 to 12 Gy per fraction [Bezjak 2019]. The maximum tolerated dose was 60 Gy (5 fractions of 12 Gy), which was associated to a 2 year local control rate of 87.9%. They reported a fatal hemoptysis rate of 4%, potentially attributable to stereotactic radiotherapy [Bejzak 2015]. Even if the authors of this prospective study reported that outcome was comparable with that of patients with peripheral early-stage tumors, the risk of severe toxicity seems to be higher than in peripheral tumors. In another prospective phase II study, the Nordic hilus trial, which included 74 patients with central tumors within 1 cm from the proximal bronchial tree (PBT), the administered dose was 8 fractions of 7 Gy [Lindberg]. The authors reported a grade 4-5 toxicity of 19% among patients with tumor close to the main bronchus (ultra-central location) versus 3% in patients with tumor close to a lobar bronchus (central location). In a retrospective study of 88 patients with ultra-central lesions defined as tumors abutting PBT or trachea, or close to esophagus, a grade 3 toxicity or higher was reported in about 20% patients [Wang]. In another smaller retrospective study, where patients received 12 fractions of 5 Gy, outcome was quite good but toxicity ≥ grade 3 was reported in 38% of patients [Tekatli]. Thereby stereotactic radiotherapy for ultra-central tumors cannot be considered a standard treatment and more studies are needed for all central tumours to find the optimal dose regimen.

      Radiological evaluation after SBRT is performed mostly with chest CT scan, and changes occurring early and/or late are very common but can be tricky for radiologists as well as clinicians [Ronden,Febbo]. If FDG PET-CT is well established as staging tool prior to treatment, it is generally not used for surveillance. It may be useful though to differentiate local recurrence from radiation-induced lung opacity. Ideally, a treatment failure suspicion should be confirmed with a biopsy.

      These hot topics regarding SBRT show the difficulty to include patients into prospective trials; efforts have been made and should be pursued.

      References

      Postmus PE, Kerr KM, Oudkerk M, et al. Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017;28(suppl_4):iv1-iv21.

      Louie AV, Senan S, Patel P, et al. When is a biopsy-proven diagnosis necessary before stereotactic ablative radiotherapy for lung cancer?: A decision analysis. Chest 2014; 146(4):1021-1028.

      Reid M, Choi HK, Han X et al. Development of a Risk Prediction Model to Estimate the Probability of Malignancy in Pulmonary Nodules Being Considered for Biopsy. Chest 2019. [Epub ahead of print]

      Lindberg K, P.Bergström, OT Brustugun et al. The Nordic HILUS-Trial - First Report of a Phase II Trial of SBRT of Centrally Located Lung Tumors. J Thorac Oncol 2017;12(15) Abstract S340.

      Bezjak A, Paulus R, Gaspar LE, et al. Safety and efficacy of a five-fraction stereotactic body radiotherapy schedule for centrally located non-small-cell lung cancer: NRG Oncology/RTOG 0813 trial. J Clin Oncol 2019;37(15):1316-1325.

      C. Wang, B. Sidiqi, E. Yorke, et al. Toxicity and local control in “ultra-central” lung tumors treated with SBRT or high-dose hypofractionated RT. J Thorac Oncol 2018; 13(10).

      Tekatli H, Haasbeek N, Dahele M, et al. Outcomes of Hypofractionated High-Dose Radiotherapy in Poor-Risk Patients with "Ultracentral" Non-Small Cell Lung Cancer. J Thorac Oncol 2016;11(7):1081-1089.

      Ronden MI, Palma D, Slotman BJ, Senan S. Brief Report on Radiological Changes following Stereotactic Ablative Radiotherapy (SABR) for Early-Stage Lung Tumors: A Pictorial Essay. J Thorac Oncol 2018;13(6):855-862.

      Febbo JA, Gaddikeri RS, Shah PN. Stereotactic Body Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer: A Primer for Radiologists. Radiographics 2018;38(5):1312-1336.

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