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J. Bogart
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MINI 37 - SCLC Therapy (ID 165)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Small Cell Lung Cancer
- Presentations: 1
- Moderators:D. Ettinger, G.R. Simon
- Coordinates: 9/09/2015, 18:30 - 20:00, 605+607
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MINI37.07 - PCI Survival Improvement for Extensive Stage SCLC Limited to Patients on Maintenance Systemic Therapy: A Secondary Analysis of CALGB 30504 (ID 861)
19:05 - 19:10 | Author(s): J. Bogart
- Abstract
- Presentation
Background:
PCI has become standard of care for extensive stage small cell lung cancer (ES-SCLC) patients. However, one recent randomized study establishing this standard did not require brain imaging prior to enrollment, and another, which did, failed to show a benefit for PCI. CALGB 30504 (Alliance) was a randomized phase II study of sunitinib vs placebo in ES-SCLC patients responding to at least 4 cycles of platinum based therapy requiring baseline brain imaging at enrollment. As this study spanned the introduction of PCI for ES-SCLC, PCI was left to the discretion of the treating team. Therefore, we performed a secondary analysis of CALGB 30504 to determine the impact of PCI on ES-SCLC patients.
Methods:
CALGB 30504 was a phase II randomized study in ES-SCLC comparing maintenance sunitinib versus placebo following SD or CR/PR to 4-6 cycles of etopside 100 mg/m[2] d1-3 and either carboplatin AUC=5 or cisplatin 80 mg/m[2] d1 q 21 days. Sunitinib was 150 mg PO d 1 then 37.5 mg PO qd until progression. The primary objective was to determine if maintenance sunitinib would improve PFS, as was recently reported. PCI was recommended at 25 Gy in 2.5 Gy fractions, within 4-6 weeks of chemotherapy, but not required. Sunitinib was to be held 2 days prior, during, and 2 days after the completion of PCI. All statistical analyses were performed by the statisticians at Alliance/CALGB Statistical and Data Center on the platform of SAS (version 9.3; SAS Institution Inc., Cary, North Carolina).
Results:
85 patients received maintenance therapy(41placebo, 44 sunitinib). 41 (48%) received PCI, 44 didn’t. All patients and tumor characteristics were balanced between PCI and no-PCI patients. PCI dose was 25 Gy for 31 patients (range: 25-37.5 Gy). Median time to PCI was 21 wks (range: 12-27 wks) from enrollment. For all patients, PCI was associated with an improvement in PFS (median 7.8 vs 6.5 mo HR=0.63 (95% CI: 0.41-0.98), p=0.037), but not OS (median 12.9 vs 13.2 mo, HR=1.01 (95% CI: 0.64-1.62), p=0.955). In placebo patients, there was no PFS or OS difference between patients receiving PCI or not. In patients randomized to sunitinib, PCI conferred a PFS benefit (9.7 vs 6.8 mo, HR=0.49 (95% CI: 0.26-0.92), p=0.024), but not an OS benefit (14.1 vs 13.5 mo, HR=0.85 (95% CI: 0.44-1.66), p=0.636). When restricted to patients who did not receive PCI, there was no difference in survival between sunitinib or placebo patients. In PCI patients, those receiving sunitinib had non-significant improvement in PFS (9.7 vs 6.7 months, HR=0.63 (95% CI: 0.34-1.20), p=0.158) and trended towards an improvement in OS (14.1 vs 10.6 months, HR=0.56 (95% CI: 0.29-1.10), p=0.087), which was magnified and approached significance when crossover patients were excluded (14.1 vs 10.0 mo, HR=0.49 (95% CI: 0.22-1.06), p=0.064).
Conclusion:
PFS, and trends for OS improvement were limited to patients receiving the combination of PCI and maintenance sunitinib. Placebo patients did not benefit from PCI. Improved outcomes for ES-SCLC patients with PCI are likely limited to patients who achieve both intracranial and extracranial disease control.
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MS 20 - Joint Imaging/Therapy Conference (ID 38)
- Event: WCLC 2015
- Type: Mini Symposium
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:O.T. Brustugun, D. Grunenwald
- Coordinates: 9/09/2015, 14:15 - 15:45, 601+603
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MS20.02 - Imaging for Radiation Therapy Planning (ID 1938)
14:40 - 15:00 | Author(s): J. Bogart
- Abstract
- Presentation
Abstract:
This session reviews considerations of imaging for radiotherapy planning and delivery with particular focus on available completed and active prospective clinical research. State - of - the - art (intensive) treatment approaches, including definitive concurrent radiotherapy and chemotherapy for locally advanced lung cancer, and stereotactic body radiotherapy for treating early stage lung cancer, depend on the ability to precisely identify sites of gross tumor and surrounding critical normal structures. As such, the incorporation of optimal anatomic and functional imaging studies, both three-dimensional (3D) and four-dimensional (4D), in the radiation planning process has become increasing critical. Prospective trials initiated in the late 1990's were the first studies assessing three-dimensional conformal radiotherapy based on computed tomography simulation. These trials directly assessed the ability to adequately dose 3D targets and permitted implementation of tissue heterogeneity dose correction. The routine inclusion of mediastinal lymph node stations that were not pathologically enlarged was also questioned in the design of these studies, and while the initial prospective study from the University of North Carolina mandated elective nodal irradiation (ENI), subsequent studies performed by the RTOG and NCCTG did not include ENI. These single arm prospective studies suggested improved survival in stage III disease with delivery of high dose conventionally fractionated radiotherapy. Somewhat surprisingly, the landmark RTOG 0617 phase III trial did not confirm these results, but perhaps refinement of target volumes through improved imaging (and treatment planning/delivery) would lead to a different result. Functional imaging with FDG-PET (/CT) has had a profound overall impact on the staging and ultimate therapy for patients with lung cancer, and radiotherapy plans are frequently altered by including FDG-PET imaging data in addition to cross sectional imaging. Moreover, while the treatment volume may be increased, such as inclusion of PET avid mediastinal lymph nodes not enlarged on CT, the radiation target volume may also be reduced particularly in instances with atelectasis or tumor obstruction. Prospective studies in the US and Europe have prospectively assessed the impact of PET on radiotherapy planning. For example, RTOG 0515 reported that PET/CT-derived tumor volumes were smaller than those derived by CT alone and that PET/CT changed nodal GTV contours in most patients. Techniques to determine the gross target volume using PET images vary and include simple visualization and a variety of software / hardware based methods including automated solutions. This remains an area of active investigtion and an understanding of potential pitfalls of PET fusion with CT simulation is necessary in defining target volumes. Retrospective series suggest a correlation between the pre-treatment standardized uptake value (SUV) and survival in patients with non-small cell lung cancer. Though the primary objective of ACRIN 6668 / RTOG 0235 was to assess post-treatment SUV for patients receiving radiotherapy as part of their treatment for stage III NSCLC, pre-treatment FDG-PET SUV (mean and max) were also assessed. While pre-treatment FDG-PET SUV did not predict outcomes, active research is assessing the delivery of differential dosing (via IMRT dose painting) based on variation in PET activity. Understanding the impact of tumor and organ motion during respiration is essential when utilizing highly conformal techniques in treating lung cancer. This is a key component of the simulation process and AAPM Task Group 76 describes various options for tumor motion management in detail. Four-dimensional CT-simulation 4D CT is accomplished by correlating the motion of an external surrogate device to the time signature of CT scans. Multiple scans are acquired during each phase of respiration and should provide sufficient motion detail to properly define the internal target volume (ITV). These phase calibrated images can then be processed into average or maximal intensity projections (MIP), or used directly as a cinema image of the tumor motion. In order to incorporate the extent of tumor motion from breathing during SBRT, contouring on the MIP, as opposed to helical or average intensity images, may be optimal. Tumor motion seen on the 4D CT is only representative of the motion at the time of simulation, so further assessment is needed to ensure this will be representative of tumor motion during the actual treatment. Real-time confirmation of tumor location during treatment, whether using the ITV method, respiratory gating, or tumor tracking may be provided by use of “cine” mode or fluoroscopy. Routine real-time imaging should be performed given the potential for variability in breathing and tumor motion over the treatment course. Image guided radiotherapy (IGRT), particularly KV cone-beam CT (CBCT) or MV – CT, is essential for ensuring accurate tumor targeting during radiotherapy. For example, image guidance capable of confirming the position of the target with each treatment was required for the RTOG 0236 trial.While the majority of clinical experience is based on 3D CBCT, 4D (respiration correlated) CBCT is now commercially available and reduces motion artifact and may have additional advantages over 3D CBCT in the treatment of lung tumors. IGRT also allows for routine assessment of tumor response and anatomic changes over time and facilitates implementation of adaptive radiotherapy approaches. Several experiences have detailed changes in tumor volume during the radiotherapy course and the (potential) impact of revising the radiotherapy plan during therapy. An ongoing prospective randomized phase II trial, RTOG 1106, is studying adaptive radiotherapy in stage III non-small cell lung cancer by incorporating changes in both functional and anatomic imaging. Repeat PET/CT and CT simulation in the midst of RT is performed for all patients on study with the “boost” volume in the experimental arm defined by the repeat PET/CT. The total dose for each patient in the experimental arm is dictated by the boost volume and predicted NTCP toxicity. The RTOG 1106 trial includes evaluation of [18]F-fluoromisonidazole (FMiso) PET imaging, which may help identify areas of hypoxia, in a subset of patients. Magnetic resonance imaging (MRI) traditionally has been reserved for assessment of select lung tumors (potentially) invading soft tissue structures such as chest wall, mediastinum, lung apex in proximity to the brachial plexus (pancoast tumors), and lesions in proximity to the spinal cord. The recent development of a commercial hybrid radiotherapy /MRI unit may expand the role of MRI and permits IGRT (without the need for additional patient exposure to ionizing radiation) while also facilitating soft tisse tracking and adaptive radiotherapy.
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