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B. Slotman
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ED14 - Small Cell Lung Cancer (ID 283)
- Event: WCLC 2016
- Type: Education Session
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:J.B. Sørensen, S. Zöchbauer-Müller
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall C2
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ED14.02 - Thoracic Radiotherapy of SCLC (ID 6502)
14:45 - 15:00 | Author(s): B. Slotman
- Abstract
- Presentation
Abstract:
Limited stage Small cell lung cancer (SCLC) comprises 10-15% of all lung tumors and is associated with an aggressive clinical behavior. Two out of three patients presents with hematogenous metastases at diagnosis (extensive stage (ES)). For patients without hematogenous metastases (limited stage (LS)), chemoradiotherapy is the standard treatment. Although radiotherapy after chemotherapy has the theoretical benefit of treating smaller target volumes with less toxicity, concurrent chemoradiotherapy has shown to be superior. Moreover, earlier use of radiotherapy during chemotherapy leads to better results. The absolute benefit of early versus late radiotherapy was about 10% for patients who had received cisplatinum-based chemotherapy [1]. Turrisi et al. [2] demonstrated that twice daily radiotherapy starting with a first course of chemotherapy resulted in improved survival rates. Median survival was 23 months for patients who received twice-daily radiotherapy (45Gy/30fractions/3weeks) versus 19 months for once daily treated patients (45Gy/25fractions/5weeks). The corresponding 5 years survival rates were 26% and 16%. However, more Grade 3-4 oesophagitis was seen during twice-daily treatment (32% versus 16%). Only a minority of patients in the US and Europe receive twice daily radiotherapy. Recently the results of the CONVERT trial, in which once-daily radiotherapy (70Gy) was compared with twice daily radiotherapy (45 Gy) were presented [3]. Radiotherapy was initiated at the 2nd course of 4-6 cycles of cisplatin/etoposide. There was no statistically significant difference in overall survival between the two arms. Overall survival at 2 years was 56% for patients treated twice-daily versus 51% for patients treated once-daily (p= 0.15) [3]. There was also no significant difference in time to progression. There were no differences in a acute toxicity, except for Grade 3-4 neutropenia, which occurred more often in the twice-daily treatment arm (74% versus 65%). There were no differences in Grade 3-5 oesophagitis (19%) and pneumonitis (2%). The authors concluded that survival in both study arms was higher than reported previously and that radiation related toxicities were lower than expected, probably related to the use of modern radiotherapy techniques. The results of the study support the use of either twice daily or once daily as standard of care for patients with limited stage disease and in good performance score. In RTOG0538 study, which also compares 70 Gy once-daily and 45 Gy twice-daily radiotherapy, radiotherapy commences with the first or second course of chemotherapy. The results of this study are eagerly awaited [4]. Extensive stage In the EORTC study on prophylactic cranial irradiation (PCI) for ES-SCLC, it was noted that the vast majority of patients still had intrathoracic disease after completion of chemotherapy. After on the positive effects of PCI which not only reduced the risk of symptomatic brain metastases (40 versus 15%) but also improved overall survival (1 year: 27 versus 13% (P= 0,003)) [5], the next logical step was to investigate the use of thoracic radiotherapy in ES-SCLC as well. Evidence for a possible role of thoracic radiotherapy (TRT) in ES-SCLC also comes from the results of a trial published by Jeremic et al. in 1999 [6] in which patients with ES-SCLC and good prognosis with a complete response outside the thorax were randomized between TRT plus PCI during chemotherapy versus chemotherapy and PCI only. Overall survival was 17 months for the patients who received thoracic radiotherapy versus 11 months for those who did not. In the CREST trial, patients with ES-SCLC and any response after 4-6 cycles of platinum based chemotherapy were randomized between PCI plus TRT (30Gy/10 fractions) or PCI only. Overall survival at one year, the primary endpoint of the study, was not statistically significant between the groups (p=0.066) but with longer follow up the survival curves diverged and at 2 years, survival was 13% in patients who received TRT versus 3% in the controls (p=0,004). There was also significant difference in progression free survival. In an additional analysis of patients with and without residual intrathoracic disease, which was one of the stratification factors of the study, it was demonstrated that there was no significant benefit of TRT in patients with a CR in the thorax. However, in patients with residual intrathoracic disease after chemotherapy, TRT led to a significant improvement in overall survival [7]. In patients who received thoracic radiotherapy the risk of intrathoracic recurrence was reduced from 80% to 44%. In patients who received thoracic radiotherapy the most recurrences occurred outside the brain and the thorax and at a later stage. The next logical step after demonstration of a beneficial effect of PCI and TRT would be the use of higher doses for TRT and possibly also treatment of extrathoracic metastatic sites. This topic was addressed in the NRG-RTOG0937 study and was presented at ASTRO 2015 [8]. patients with ES-SCLC and a CR or PR after chemotherapy and 1-4 metastatic lesions were randomized between PCI or PCI plus TRT plus radiotherapy of metastatic sites. The study which accrued very slowly was closed early due to observed toxicities. The study did not show a survival difference between the two groups, but included only 86 patients over a five years period and had imbalance groups with worse prognostic factors in the experimental arm. There were many, partly unrelated, Grade 4-5 toxicities in the experimental arm. To define which patients are most likely to benefit from a more aggressive approach we have performed an additional analysis for patients from the top accruing centers from the CREST trial. An evaluation of 260 patients showed significantly better outcome in patients with 0 to 2 metastases versus and without liver metastases [10]. These patients are believed to be best candidates for future studies. References 1. Fried DB, Morris DE, Poole C, et al. Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer. J Clin Oncol 2004. 22, 4837-45. 2. Turrisi AT 3rd, Kim K, Blum R, et al. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. 1999 340, 265-71. 3. Faivre-Finn C, Snee M, Ashcroft L. CONVERT: An international randomised trial of concurrent chemo-radiotherapy (cCTRT) comparing twice-daily (BD) and once-daily (OD) radiotherapy schedules in patients with limited stage small cell lung cancer (LS-SCLC) and good performance status (PS). ASCO Meeting abstracts J Clin Oncol 2016, 8504. 4. Slotman BJ, Senan S; Radiotherapy in small-cell lung cancer: Lessons learned and future directions. Int J Radiat Oncol Biol Phys 2011, 79, 998-1003. 5. Slotman BJ, Faivre-Finn C, Kramer G. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 2007, 357, 664-72. 6. Jeremic B, Shibamoto Y, Nikolic N, et al. Role of radiation therapy in the combined- modality treatment of patients with extensive disease small-cell lung cancer; A randomized study. J Clin Oncol 1999,17, 2092-9. 7. Slotman BJ, van Tinteren H, Praag JO, et al., Use of thoracic radiotherapy for extensive stage small-cell lung cancer: a phase 3 randomised controlled trial. Lancet 2015, 385, 239-44. 8. Slotman BJ, van Tinteren H. Which patients with extensive stage small-cell lung cancer should and should not receive thoracic radiotherapy? Transl Lung Cancer Res. 2015, 4, 292-4. 9. Gore EM, Hu C, Sun A, et al. NRG Oncology/RTOG 0937: Randomized phase II study comparing prophylactic cranial irradiation (PCI) alone to PCI and consolidative extra-cranial irradiation for extensive disease small cell lung cancer (ED-SCLC). Proc ASTRO, Int J Radiat Oncol Biol Phys 2016, 94, 5.
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MA13 - Modern Technologies and Biological Factors in Radiotherapy (ID 395)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Radiotherapy
- Presentations: 1
- Moderators:M. Thomas, P. Mitchell
- Coordinates: 12/06/2016, 16:00 - 17:30, Stolz 1
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MA13.10 - Magnetic Resonance Imaging-Guided Delivery of Lung Stereotactic Radiotherapy Using Patient-Controlled Visual Guidance (ID 5293)
17:00 - 17:06 | Author(s): B. Slotman
- Abstract
- Presentation
Background:
Treatment-related toxicity is more common following stereotactic ablative radiotherapy (SABR) for central lung tumors, than is the case for peripheral tumors [Tekatli 2015]. Further reductions in doses to critical central structures are possible using respiration-gated SABR delivery, but insertion of fiducial markers for gating is also associated with toxicity. We describe a novel approach for clinical delivery of breath-hold gated SABR under continuous MRI-guidance.
Methods:
The MRIdian® system permits tumor visualization at 4 frames/second during treatment delivery, with radiation beam-holds whenever the target is outside a prespecified gating window. The gating procedure is as follows: a 17 second inspiration breath-hold MR scan is performed for planning before each SABR fraction (resolution 1.6×1.6×3.0 mm). Image registration is performed, and contours adapted when necessary. A 3mm PTV margin is added, and planned dose distribution recalculated for the ‘anatomy of the day’, and reoptimized. A sagittal plane is chosen for tumor tracking and gating, with a planning target margin of 3 mm. The sagittal tracking view from the MRIdian console is projected on a MR-safe monitor (Cambridge Research), and patients can continuously observe the tracking image using a mirror inside the bore.
Results:
Since May 2016, 30 fractions of MR-guided gated delivery have been performed in 5 cancer patients with 6 central tumors. All MR-based breath-hold PTV’s were smaller (mean 19.8 ± 13.3 cc) than a conventional free-breathing, motion-encompassing approach (mean 36.1 ± 21.9 cc). Plans of a single case are shown in Figure 1. Video-assisted visual feedback achieved a breath-hold gating efficiency of 52% (range 27-88%).Figure 1
Conclusion:
For high-risk SABR cases, use of MR-guided, video-assisted breath-hold gated SABR delivery constitutes a novel treatment method, allowing for minimization of mobility- and setup margins, and for improved verification of SABR delivery. Data from additional patients undergoing treatment will be presented.
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