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F. Lagerwaard



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    E08 - Early Endobronchial Tumours (ID 8)

    • Event: WCLC 2013
    • Type: Educational Session
    • Track: Pulmonology + Endoscopy/Pulmonary
    • Presentations: 1
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      E08.4 - RT Approaches for Early Stage Central Tumours (ID 411)

      15:05 - 15:25  |  Author(s): F. Lagerwaard

      • Abstract
      • Presentation
      • Slides

      Abstract
      Stereotactic ablative radiotherapy (SABR) is an established treatment modality in the curative treatment of early stage peripheral non-small cell lung cancer (NSCLC). The local control rates of SABR in many publications have exceeded 90% when tumors of up to 5 cm were treated, with corresponding regional nodal failure rates of approximately 10%. SABR has been reported in many series to have only modest early and late toxicity, generally maintaining pulmonary function and preserving health-related quality of life. Following the publication of an phase II study, which showed an 11-fold increase in severe toxicity in the subgroup of patients with centrally located lung tumors that had been treated with a high dose per fraction, these central locations had been considered to be a ‘no fly zone’ for SABR [Timmerman 2006]. Although several subsequent single center studies have shown that SABR performed with an adapted fractionation scheme using daily fractions of 6.0–7.5 Gy to total doses of 48–60 Gy has been both effective and safe, the results of the ongoing Radiation Therapy Oncology Group (RTOG) phase II trial (0813) for SABR in central tumors, have to be awaited to determine the maximum tolerated dose which can be delivered in five fractions. A recently published systematic review of the literature identified a total of 20 studies reporting on the outcome of SABR in 315 patients with centrally located early stage NSCLC, including two phase II studies [Senthi 2013]. The overall survival rates reported for centrally located tumors appeared to be similar to those of peripheral tumors. Similar to what has been described for peripheral lesions, central tumors showed a dose–response relationship for local control, with four studies reporting improved outcomes with a biological effective dose of 100 Gy~10~ or higher compared to lower doses. In those studies where fractionation schedules with a biological effective dose of 100 Gy~10~ or higher were used, the local control rates exceeded 85%. Post-SABR grade 3 or 4 toxicity occurred in 8.6% of central tumors treated with SABR, and the risk of treatment-related mortality was less than 1% if the biological effective dose for late responding tissues (BED Gy~3~) remained below 210 Gy~3~. In conclusion, SABR for central tumors has been shown to be both effective and safe, provided that appropriate risk-adapted fractionation schemes are used and careful contouring of organs at risk with quality assurance of all aspects of treatment planning and delivery are taken into account. The results of the RTOG dose-finding phase II study 0813, in which already 120 patients are entered, will further strengthen the data on the use of SABR for centrally located tumors.

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    P2.08 - Poster Session 2 - Radiotherapy (ID 198)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      P2.08-012 - Treatment of Multiple Primary Lung Cancers (MPLC) with stereotactic ablative radiotherapy (SABR) (ID 1394)

      09:30 - 09:30  |  Author(s): F. Lagerwaard

      • Abstract

      Background
      Multiple primary lung cancers (MPLC) are not an uncommon clinical presentation, with an incidence in the surgical literature of 1-8%. ESMO guidelines state that synchronously detected lesions should be treated as multiple primary tumors, and a curative approach for both lesions has been associated with improved survival in the surgical series. However, many patients with MLCP are elderly and have multiple co-morbidities, which can render them unfit to undergo surgery for both lesions. We analyzed clinical outcomes in such patients who were treated with SABR.

      Methods
      SABR was performed in 62 patients diagnosed with MPLC at the VUmc from 2003 – 2012. Staging included a mandatory FDG-PET scan, and all patients were discussed in a multi-disciplinary tumor board. A pathological diagnosis was available for both lesions in 3%, and for one lesion in 48%. Invasive nodal staging was performed in 13% of patients. SABR was used as a single modality for both lesions (n=56), or in combination with surgery for the second lesion (n=6). SABR was delivered to a total dose of 54-60 Gray (Gy) in 3-8 fractions, depending on tumor size and location. Clinical outcome, including survival, patterns of relapse and toxicity (CTC v4.0) was evaluated. A sub-analysis was performed for ipsilateral and bilateral lung lesions.

      Results
      Median overall survival was 31 months, with an actuarial survival of 56% at 2 years. Overall lesion local control rate was 84% at 2 years. Local control correlated significantly with number of fractions (p=0.013) and lesion location (p=0.004) on univariable Cox regression analysis. Lesion control at 2 years for bilateral lesions was 92% versus 74% for ipsilateral lesions (p=0.009). Regional failures at two years were observed in 13% (n=6) of all patients, and in 0% versus 31% in patients with respectively bilateral and ipsilateral lesions. Of the patients who developed a subsequent regional recurrence, only one had undergone EUS/EBUS prior to treatment, and others did not as pre-treatment FDG-PET-scans showed no nodal uptake. Distant failures were observed in 27% of all patients, at two years. No grade ≥3 early toxicity was observed. Late grade 3 toxicity was reported in 3 patients (5%), consisting of pneumonitis (n=1), rib fracture (n=1) and chest wall pain (n=1). No grades 4-5 late toxicity was reported.

      Conclusion
      Curative treatment of MPLC using SABR, either alone or combined with surgery, can lead to long-term survival with limited toxicity. The disappointing local control rates observed after SABR for ipsilateral double lesions merits further investigation. The higher rate of nodal recurrences in patients presenting with multiple ipsilateral lesions suggests that systematic nodal staging may be appropriate in such cases.

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    P3.09 - Poster Session 3 - Combined Modality (ID 214)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 1
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      P3.09-004 - Oligometastatic non-small cell lung cancer: a simulation expert multidisciplinary tumor board. (ID 1122)

      09:30 - 09:30  |  Author(s): F. Lagerwaard

      • Abstract

      Background
      Series on aggressive local treatment in selected patients with oligometastatic non-small cell lung cancer (NSCLC) are mostly retrospective, and prospective data are scarce (De Ruysscher et al, JTO 7:1547-1555, 2012). Although a precise definition is lacking, ‘oligometastatic NSCLC’ is considered an intermediate biologic state of restricted metastatic capacity with a limited number of metastases. The turning point between oligometastatic and polymetastatic is merely based on personal opinion and situated somewhere between 1 and 5 distant metastases. In the absence of clear definitions or clinical practice recommendations, a treatment decision is mainly driven by the opinion of each local multidisciplinary tumor board (MDTB).

      Methods
      As the consideration of and the treatment modality for oligometastatic NSCLC is a controversial area in respiratory oncology, in preparation of a recent dedicated workshop, we simulated a MDTB with international experts in the field. Multiple disciplines from 7 different centers participated in the MDTB, including pathology (1), nuclear medicine physician (1), thoracic surgery (3), radiation oncology (3), and respiratory oncology (3). Participants were asked to assess an electronic file describing 10 clinical ‘oligometastatic NSCLC’ cases, with 2 simple questions per case: 1. Do you consider this case ‘oligometastatic’ (Yes/No) and 2. What is your preferred treatment proposal.

      Results
      A full response was returned by all 11 specialists taking part in the simulated MDTB. Only 1 case was considered ‘oligometastatic NSCLC’ by all MDTB members. The presented cases were considered by a median of 78% (range 36-100%) of responders as true oligometastatic disease. Despite the fact that each responder gave only one treatment proposal, a median of 4 different treatment proposals (range 2-6) was made per case. Except for brain metastases, most team members would treat the locoregional thoracic disease before the distant metastases. No preference towards neo-adjuvant or adjuvant chemotherapy could be found. The option for surgery or radiation therapy as part of a combined modality treatment was mainly driven by the physicians’ preference.

      Conclusion
      Our simulated MDTB shows that oligometastatic NSCLC is an entity with many unanswered questions, and thus a major challenge for clinicians. Patients with oligometastatic NSCLC are in the need of 1. discussion at an experienced multidisciplinary tumor board to select patients for a radical combined modality approach; 2. multidisciplinary prospective research protocols to set better definitions of oligometastic NSCLC, evaluate the validity of a radical approach, and to optimize therapeutic modalities.