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M. Dahele



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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): M. Dahele

      • 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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    MO17 - Radiotherapy I: Stereotactic Ablative Body Radiotherapy (ID 106)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      MO17.10 - Late radiologic change after stereotactic ablative radiotherapy for early stage lung cancer: A comparison between fixed-beam versus arc delivery techniques (ID 1405)

      17:10 - 17:15  |  Author(s): M. Dahele

      • Abstract
      • Presentation
      • Slides

      Background
      Treatment-related radiologic change occurs commonly following stereotactic ablative radiotherapy (SABR) and often confound the interpretation of follow-up CT scans. SABR is frequently delivered using both fixed-beams and rotational-arcs, resulting in different dose distributions and it is unclear how this influences radiological change. We studied the morphology, timing and severity of radiologic change after both delivery techniques.

      Methods
      Twenty-nine patients with early stage non-small cell lung cancer receiving SABR by arc delivery, without clinical evidence of local recurrence, and a follow-up of more than two years, were assessed using a published scoring system [Dahele M, JTO 2011]. Here, the morphology of acute (within six months) radiologic change was characterized between ‘patchy (less than 5 cm) ground glass opacity’, ‘patchy consolidation’, ‘diffuse (more than 5 cm) ground glass opacity’, or ‘diffuse consolidation’. The late (after 6 months) morphology was characterized between ‘scar-like’, ‘mass-like’ and ‘modified conventional’. Additionally the severity of radiologic change was scored as ‘pronounced’ (more than expected), ‘expected’, ‘mild’ (less than expected) and none. These outcomes were compared to 54 patients treated with SABR by fixed-beam delivery, who we previously assessed using the same scoring system.

      Results
      Baseline characteristics of the arc and fixed-beam cohorts were well matched and respective median follow-ups were no different, 31.7 vs. 28.4 months (p=0.20). Patients treated by arc delivery trended towards being more likely to have any radiologic change (p=0.06). This was strongly time-dependent (p<0.001) and more pronounced early, as by two years radiologic changes were almost universally present irrespective of delivery technique. Figure 1 shows the morphology of these changes with time. Acute changes were not technique dependent (p=0.23). After six months, arc delivery resulted in a modified-conventional morphology throughout follow-up, while fixed-beam delivery resulted in an increasing probability of scar-like or mass-like morphologies. The predicted probabilities of a modified-conventional pattern following SABR by arc and fixed-beam delivery were 96.3% vs. 68.9% (p<0.001) respectively. Following arc delivery, radiologic changes were more likely to be scored as pronounced or expected (p=0.009) than mild or none, a finding that became more evident with longer follow-up (p=0.014). The predicted probability of pronounced or expected changes two years following arc or fixed-beam delivery was 83.1% and 26.2%, respectively. Figure 1

      Conclusion
      Patterns of radiologic change more than six months post-SABR are influenced by delivery technique. Diagnostic algorithms used to differentiate suspected local recurrence and benign change should therefore consider the delivery technique used.

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    P3.08 - Poster Session 3 - Radiotherapy (ID 199)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
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      P3.08-017 - High-dose, conventionally fractionated thoracic reirradiation for second primary lung tumors or recurrent disease (ID 2335)

      09:30 - 09:30  |  Author(s): M. Dahele

      • Abstract

      Background
      Although loco-regional recurrences and second primary lung tumors are not uncommon following prior high-dose thoracic radiotherapy, only a minority of patients undergo reirradiation. Reirradiation performed at short intervals, and to low total doses, is generally associated with median overall survival (OS) of only 5-7 months. Few studies report outcomes following high-dose reirradiation. We describe institutional experience after high-dose, conventionally fractionated reirradiation.

      Methods
      High-dose conventional reirradiation was defined as fraction sizes of 2-3Gy and minimum total dose of 39Gy. A retrospective chart review of patients treated between Feb 2004-Feb 2013 was performed. Where possible, overlap in planning target volumes (PTV) and radiation doses were determined. New primary tumors were defined as new histology or reirradiation interval ≥5 years.

      Results
      24 patients were identified, 13 (54%) had recurrent disease, and 46% a new primary. Most (63%) had stage III NSCLC at initial and second treatments; median reirradiation interval was 51 months, and median follow-up from reirradiation 19.1 months. Median overall survival (OS) after reirradiation was 13.5 months, with 1-year survival 51%, median local progression-free survival (LPFS) 14.1 months and median distant progression-free survival (DPFS) 18.5 months. One-year disease-free survival was 47%. Three patients died from bleeding (2/3 had high-dose overlap in the mediastinum, of whom one had prior hemoptysis and was anticoagulated, the 3rd patient had extensive endobronchial therapy prior to reirradiation). Other post-retreatment toxicity was uncommon. The size of the second PTV (median 250cc) was prognostic. OS was 17.4 versus 8.2 months for patients with a 2nd PTV <300cc and >300cc respectively (p=0.02). Differences in DPFS (p=0.007) and for DFS (p=0.03) were also significant. LPFS was shorter when reirradiation interval was <24 months (p=0.02), however it was not different when groups were defined by the median interval of 51 months. Magnitude of PTV and dose overlap between the two treatments did not influence survival. Figure 1 Figure 1: Example of reirradiation for a new primary lung cancer. Planning target volume (PTV) and dose-cloud shown from treatment in 2004 (A, 23 fractions of 2.6Gy) and 2010 (B, 33 fractions of 2Gy) and the overlap of both treatments (C).

      Conclusion
      High-dose, conventionally fractionated reirradiation for new primary or recurrent lung cancer can deliver meaningful survival, especially for patients with a smaller PTV at the time of reirradiation. A shorter reirradiation interval may be associated with less chance of loco-regional control. Prospective studies are needed to confirm these findings, and establish reliable normal tissue tolerances for reirradiation.

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    P3.12 - Poster Session 3 - NSCLC Early Stage (ID 206)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P3.12-013 - Radical treatment of synchronous oligometastatic non-small cell lung carcinoma (NSCLC): patient outcomes and prognostic factors. (ID 2315)

      09:30 - 09:30  |  Author(s): M. Dahele

      • Abstract

      Background
      In general, metastatic NSCLC has a poor prognosis and systemic therapy is the cornerstone of treatment. However, extended survival has been reported in some patients presenting with a limited number of metastases, termed oligometastatic disease. The goal of this study was to assess outcomes for patients presenting with NSCLC and synchronous oligometastases, treated with radical intent, and to determine predictors of long-term survival.

      Methods
      A retrospective chart review was undertaken at two cancer centres, on patients with NSCLC presenting with 1-3 metastasis, who received radical intent treatment (surgery and/or radiotherapy (RT) ± chemotherapy) to the primary lung tumor including the pathological regional nodes and all sites of metastatic disease. Overall survival (OS), progression-free survival (PFS) and survival after first progression (SAPF) were evaluated. Recursive partitioning analysis (RPA) was performed based on significant factors from univariable analysis to identify different risk groups.

      Results
      Between 1999 and 2012, 61 patients were treated with a total of 74 metastases. Median follow-up was 26 months. Patients had a median age of 62 years, a median performance status of 1 and intrathoracic disease that was predominately stage III (n=38). The majority of patients had a solitary metastasis (n=50). Common sites of metastases were brain (n=47 lesions), bone (n=11), adrenal (n=4), contralateral lung (n=4) and extrathoracic lymph nodes (n=4). Treatment of the primary tumor consisted of RT ± chemotherapy in 52 patients and surgery alone or in combination with other modalities in 9 patients. Metastases were treated with stereotactic or high-dose RT (n=39) or surgery (n=22). Median OS was 13.5 months, 2-year OS was 38%. Median PFS was 6.6 months and median SAFP was 4.9 months. Predictors of improved survival were surgery for the primary lung tumor (p<0.001), and intrathoracic PTV size in patients receiving RT (p<0.03). These factors were used for RPA (Figure 1). No significant differences in outcomes were observed between the two centers. Figure 1 Figure 1. RPA flowchart for OS showing characteristics of risk groups (A) with accompanying Kaplan-Meier curves of OS by RPA risk groups (B)

      Conclusion
      Radical treatment of selected NSCLC patients presenting with 1-3 synchronous metastases can result in favorable 2-year survival, although progression in the first year was common. Outcomes were strongly associated with intra-thoracic disease status: patients with small radiotherapy treatment volumes or resected disease had the best OS. Prospective clinical trials, ideally randomized, should evaluate the role of radical treatment strategies in patients with oligometastases.