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P. Iyengar
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ORAL 19 - Radiation for Localized Lung Cancer (ID 126)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:D. De Ruysscher, M. Hiraoka
- Coordinates: 9/08/2015, 10:45 - 12:15, 102+104+106
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ORAL19.03 - NRG Oncology/RTOG 0813 Trial of Stereotactic Body Radiotherapy (SBRT) for Central Tumors - Adverse Events (ID 1458)
10:45 - 12:15 | Author(s): P. Iyengar
- Abstract
- Presentation
Background:
The safety of SBRT for medically inoperable patients with centrally located early stage non-small cell lung cancer (NSCLC) was evaluated in this phase I/II multicenter RTOG study that completed accrual in Sept 2013. This is the first report of adverse events (AE) observed on the study.
Methods:
Eligible patients were medically inoperable with biopsy proven, PET staged T1-2N0M0 NSCLC, ≤ 5 cm in size, centrally located tumors (within or touching the zone of the proximal bronchial tree or adjacent to mediastinal or pericardial pleura). Patients were successively accrued onto dose-escalating 5 fraction SBRT schedules delivered over 1.5-2 weeks, starting with 10 Gy per fraction (fr), then 10.5Gy/fr, 11 Gy/fr, 11.5 Gy/fr and 12 Gy /fr. Toxicity was graded using CTCAE v4.0; any potential dose-limiting toxicity within the initial 365 days post SBRT could have led to dose reduction for subsequent patients accrued, using TITE-CRM (time-to-event continual reassessment method) statistical design.
Results:
120 patients (100 evaluable) from 43 centers were accrued between 2/2009 and 9/2013. 12 were excluded as they did not receive protocol treatment (6 of these on the 12Gy/fr cohort) and another 8 did not meet eligibility criteria. Cohort sizes were 8 (10Gy/fr), 8 (10.5Gy/fr), 18 (11Gy/fr), 43 (11.5Gy/fr), and 43 pts (12Gy/fr). Median age was 72 (range 52- 89) years, 57% were female, 45% had squamous cell carcinoma, 39% had adenocarcinoma, 65% had T1 tumors. Median follow up was 26.6 months. Most adverse events were grade (G) 1 or 2. 5/8 pts in lowest SBRT dose cohort (10 Gy/fr) experienced G2 toxicity, none had G>3. Of 7 pts in 10.5 Gy/fr, 1 had G2 and 1 had G5 toxicity. Of 14 pts in 11 Gy/fr cohort, 4 had G2 and 1 had G3. Of 38 pts in 11.5Gy/fr cohort, 11 had G2, 4 had G3 and 2 had G5. Of 33 pts in 12Gy/fr, 4 had G2, 5 had G3, 1 G4 and 1Gr 5 as the worst overall toxicity definitely, probably or possibly related to SBRT. All Gr 5 toxicities were due to hemoptysis, occuring at a mean of 13 mo post SBRT (range 5.5-14mo). G2+ GI toxicity only occurred in the 11.5Gy/fr (1/38) and 12.0Gy/fr (2/33) cohorts. G2+ pulmonary toxicity occurred in 4/8 10.0Gy/fr, 0/8 10.5Gy/fr, 5/14 11.0Gy/fr, 15/38 11.5Gy/fr, and 10/33 12.0Gy/fr pts.
Conclusion:
This phase I/II trial of SBRT provides data to inform patients of the potential toxicities with a 5 fraction SBRT schedule for centrally located NSCLC. Although SBRT was well tolerated, 4/100 pts (4%) had fatal hemoptysis potentially attributable to SBRT. Determination of the optimal SBRT dose needs to await analysis of tumor locations, DVH data and efficacy data. This project was supported by grants U10CA21661, U10CA180868, U10CA180822 and U10CA37422 from the National Cancer Institute (NCI).
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ORAL 20 - Chemoradiotherapy (ID 124)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:G. Blumenschein, J.Y. Chang
- Coordinates: 9/08/2015, 10:45 - 12:15, 201+203
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ORAL20.06 - Outcomes of Intensity Modulated and 3D-Conformal Radiotherapy for Stage III Non-Small Cell Lung Cancer in NRG Oncology/RTOG 0617 (ID 938)
10:45 - 12:15 | Author(s): P. Iyengar
- Abstract
Background:
Intensity modulated radiation therapy (IMRT) has the potential to improve target coverage and spare toxicity in locally-advanced non-small cell lung cancer (NSCLC). However, the effect of IMRT on outcomes for NSCLC has not previously been assessed in a large prospective cooperative group clinical trial.
Methods:
A secondary analysis was performed in patients with stage III NSCLC in NRG/RTOG 0617, a randomized phase III comparison of standard-dose (60 Gy) versus high-dose (74 Gy) chemoradiotherapy +/- cetuximab. Radiotherapy (RT) technique was stratified by IMRT and 3D-conformal radiotherapy (3D-CRT). Baseline prognostic and RT dosimetric parameters were compared between IMRT and 3D-CRT after adjusting for RT dose levels and cetuximab use. The prognostic value of RT technique with respect to toxicity and efficacy was assessed through multivariate logistic regression (MVA) and Cox proportional hazards model after controlling for RT dose level, cetuximab use and other factors.
Results:
Of the 482 eligible patients treated with RT, 53% and 47% were treated with 3D-CRT and IMRT, respectively. The IMRT group had more stage IIIB (38.6 vs. 30.3%, P = 0.056), larger PTVs (mean 486 vs. 427 mL, P = 0.005), and larger PTV:lung ratio (mean 0.15 vs. 0.13, P = 0.013). In spite of larger PTV volumes, IMRT was associated with lower lung V20 (P = 0.08), and lower heart doses (V5, V20, V40) than 3D-CRT. In turn, IMRT was associated with a lower rate (3.5 versus 7.9%) of Grade 3+ pneumonitis (P = 0.0653). On MVA, the lung V20 significantly predicted grade 3+ pneumonitis, while the lung V5 and mean lung doses did not. Larger heart V40 was associated with worse OS (HR=1.013, P < 0.001), and the heart V40 was significantly lower in patients treated with IMRT. Patients treated with IMRT were also more likely (37 versus 29%) to receive full doses of consolidative chemotherapy (P = 0.05).
Conclusion:
Although IMRT was used to treat larger and less favorable tumors in RTOG 0617, it was associated with reduced risk of Grade 3+ pneumonitis and higher likelihood of receiving full doses of consolidative chemotherapy. The heart V40, shown to be highly prognostic for survival, can be substantially reduced with IMRT compared to 3D-CRT.
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P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.01-068 - Randomized Trial of Maintenance Chemotherapy Versus SBRT plus Maintenance Chemotherapy for Advanced NSCLC - Feasibility and Early Outcomes (ID 932)
09:30 - 17:00 | Author(s): P. Iyengar
- Abstract
Background:
Following first-line chemotherapy, maintenance therapy regimens have shown modest yet statistically significant benefits in progression free survival (PFS). To date, there have been no completed, prospective randomized trials examining the role of locally aggressive therapy in limited metastastic, advanced stage non-small cell lung cancer (NSCLC). We hypothesized that stereotactic body radiotherapy (SBRT) prior to maintenance chemotherapy would further improve PFS. This trial also serves to provide prospective survival data for a population with limited metastatic NSCLC.
Methods:
This is a two-arm randomized phase II trial. Eligible patients have stable disease or partial response with limited metastatic disease (defined by six or fewer sites amenable to SBRT) after treatment with up to 6 cycles of first line platinum doublet chemotherapy. Patients are then randomized to investigator’s choice maintenance chemotherapy alone or SBRT to all amenable sites followed by maintenance chemotherapy. The primary endpoint of the study is PFS, with 36 patients required to demonstrate an increase from 4 months in the control arm to 10 months in the experimental arm, with 80% statistical power and a 2-sided significance level of 0.10.
Results:
Since May 2014, 11 patients have been enrolled (5 to SBRT + maintenance arm; 6 to maintenance arm). The median number of first-line chemotherapy cycles was four, with the most common regimen carboplatin/paclitaxel followed by carboplatin/pemetrexed. The median number of maintenance chemotherapy cycles was six, the most common agent being pemetrexed followed by bevacizumab. The median number of sites treated with SBRT were two, with the lung the most common anatomic location followed by the adrenal gland. Five patients have progressed to date, three in the maintenance chemotherapy arm and two in the SBRT + maintenance chemotherapy arm. Progression in the maintenance alone arm occurred in original sites of disease in two of three patients. There have been no in-field failures in the SBRT arm. There has been one death due to disease progression in the maintenance chemotherapy arm. No patients have suffered a grade 3 or higher adverse event related to protocol therapy.
Conclusion:
This study demonstrates the feasibility of enrolling patients with limited metastatic lung cancer to a randomized trial of local therapy following first-line chemotherapy. To date, all patients have tolerated the administration of SBRT to multiple sites in between first-line and maintenance chemotherapy without any grade 3 or higher adverse events. Continued follow-up will be necessary to determine the efficacy of the experimental arm.
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P1.11 - Poster Session/ Palliative and Supportive Care (ID 229)
- Event: WCLC 2015
- Type: Poster
- Track: Palliative and Supportive Care
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.11-003 - New Clinical and Biologic Insight Into Lung Cancer-Associated Cachexia From a Large Cohort Study (ID 1085)
09:30 - 17:00 | Author(s): P. Iyengar
- Abstract
Background:
Cancer cachexia (CC) is a wasting syndrome without durable palliative intervention observed in 50% of all solid tumors and responsible for 20-30% of all cancer-related deaths. Knowledge of prevalence and survival outcomes for lung CC patients by clinical and pathologic parameters is scarce due to limited series. We provide the largest, most detailed evaluation of lung cancer patients for cachexia, enabling new clinical and biologic insight.
Methods:
A retrospective review of 1627 patients with non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) treated at UT Southwestern Medical Center between 1/1/2006 and 12/31/2013 was performed. Patient demographics and tumor characteristics including histology, stage, grade, and size were collected. Each patient was assessed for CC at diagnosis, retrospectively identified by the presence of significant weight loss (>5% loss over 6 months in patients with BMI >= 20; >2% in patients with BMI <20). Overall Survival (OS) was evaluated, and clinicopathologic factors predicting for cachexia development were identified with stepwise logistic regression (SLR).
Results:
Overall, CC independently predicted reduced OS on stepwise Cox regression (1.21 OR). 419/1468 (28.5%) of all NSCLC and 57/159 (35.8%) of all SCLC patients had CC. Within NSCLC, CC was documented in 107/350 (30.6%) of squamous carcinomas and 208/761 (27.3%) of adenocarcinomas. CC significantly reduced NSCLC OS across all stages: 21.0 vs. 9.9 months (log-rank P<0.0001). However, CC did not significantly affect SCLC OS: 10.5 vs. 9.9 months (log-rank P=0.46). Prevalence of CC in NSCLC for stages 1, 2, 3, and 4 was 48/309 (15.5%), 16/124 (12.9%), 118/377 (31.3%), and 237/658 (36.0%), respectively. OS for NSCLC -/+ CC for stages 1, 2, 3, and 4 were 67.1 vs. 45.0, 35.4 vs. 37.2, 20.9 vs. 14.3, and 11.4 vs. 6.6 months, respectively (log-rank P=0.0427, =0.5803, =0.0155, <0.0001). OS for squamous histologies -/+ CC for stages 1, 2, 3, and 4 were 56.9 vs. 22.7, 19.3 vs. 19.5, 18.6 vs. 14.3, and 7.8 vs. 5.8 months, respectively. OS for adenocarcinoma histologies -/+ CC for stages 1, 2, 3, and 4 were 86.4 vs. 51.1, 43.9 vs. 23.3, 28.6 vs. 19.2, and 13.0 vs. 8.2 months, respectively. On univariate analysis, grade, stage, tumor size, and tobacco use were significant factors in the development of CC in adenocarcinomas, while stage alone was significant in squamous carcinomas. On SLR, stages 3+4 were associated with increased odds of CC development as compared to stages 1+2 (OR 2.6, P=0.0004) in squamous histologies. On SLR, tumor size >50mm was associated with increased odds of CC development when compared to 0-20 mm (OR 4.3, P<0.0001) in adenocarcinomas.
Conclusion:
Cachexia significantly impacts OS in lung cancer, primarily for NSCLC. Fundamental differences of CC prevalence and associated OS were observed for the first time between different histologies and stages. Though CC can manifest in all stages, increased stage and tumor size were independent, significant predictors for CC in squamous and adenocarcinoma populations, respectively. Understanding which clinicopathologic characteristics impact CC prevalence and OS may offer insight into the syndrome’s clinical and biologic underpinnings, providing impetus for novel therapeutics and prediction methods.
