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M. Hiraoka
Moderator of
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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: 8
- Moderators:D. De Ruysscher, M. Hiraoka
- Coordinates: 9/08/2015, 10:45 - 12:15, 102+104+106
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ORAL19.01 - The SPACE Study: A Randomized Phase II Trial Comparing SBRT and 3DCRT in Stage I NSCLC Patients; Final Analysis including HRQL (ID 923)
10:45 - 10:56 | Author(s): A. Hallqvist, J.A. Lund, O.T. Brustugun, B. Bergman, P. Bergström, S. Friesland, R. Lewnsohn, N. Drugge, H. Rylander, I. Lax, E. Holmberg, J. Nyman
- Abstract
- Presentation
Background:
Stereotactic body radiotherapy (SBRT) for NSCLC patients with T1-T2 tumors has been intensively studied the last decades and is widely used due to excellent results in terms of local control and survival in combination with the convenient and fast treatment procedure. This radiation technique has however never been compared to standard radiotherapy in a randomized manner, and consequently the Swedish lung cancer study group launched the SPACE study in 2007 (Stereotactic Precision And Conventional radiotherapy Evaluation).
Methods:
Patients with stage I medically inoperable histologically confirmed NSCLC or PET-positive tumors with progression (non-centrally located with a maximum size < 5 cm) were randomized in 9 Scandinavian centers to receive SBRT to 66 Gy in 3 fractions in one week or conventionally fractionated 3DCRT to 70 Gy in 7 weeks. Patients were followed with regard to treatment efficacy, toxicity and HRQL.
Results:
Between January 2007 and July 2011 102 patients were randomized (49 SBRT, 53 3DCRT). Mean age 74 (57-86), 60% women and the vast majority (92%) had COPD or cardiovascular comorbidity. The mean FEV1 and mean CO-diffusion capacity were 1.4 L and 55% respectively. Seventy-four percent had a histopathologic diagnose where the majority were adenocarcinomas and 65% had T1 tumors and 35% T2. The two treatment groups differed somewhat in terms of tumor size and gender where the SBRT arm included more patients with T2 tumors and of male gender. The median follow-up is 37 months with a 1- 2- and 3 year PFS of: SBRT: 89%, 70%, 62% and 3DCRT: 88%, 66% 58% with no difference between the groups and no difference regarding OS. At the end of study 72% were without progression among the SBRT patients compared to 59% in the conventional arm. Toxicity was generally low, grade ≥ 3 of any toxicity was observed in 19% in SBRT patients and 15% in the 3DCRT group with no grade 5 toxicities. Pneumonitis of any grade was observed in 19% (SBRT) and 36% (3DCRT), and any grade esophagitis in 8% and 30% respectively. HRQL was evaluated with the EORTC QLQ 30 and LC14 module and patients treated with 3DCRT experienced worse dyspnea, cough and chest pain compared to the SBRT patients.
Conclusion:
NSCLC stage I patients treated with SBRT had the same PFS and OS as the conventionally treated patients despite an imbalance of prognostic factors with regards to more T2 tumors and males in the SBRT group. There was a tendency to improved disease control rate in the SBRT patients and in addition they experienced higher QoL values regarding dyspnea, cough and chest pain. SBRT should be considered standard therapy for this patient group.
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ORAL19.02 - Higher Risk of Failure and Death after Stereotactic Lung Radiotherapy for T2 Lung Cancer (ID 2945)
10:56 - 11:07 | Author(s): I. Grills, J. Belderbos, A. Hope, M. Werner-Wasik, M.D. Johnson, H. Peulen, M. Giuliani, J. Sonke, H. Ye, M. Guckenberger
- Abstract
- Presentation
Background:
Limited data are available on the use of SBRT for tumors larger than 3cm. We analyzed results from a collaborative database to compare clinical outcomes for patients with tumors > 3cm to those with smaller tumors (<3cm).
Methods:
1192 patients with 1288 T1-T3N0M0 tumors underwent cone-beam CT image-guided lung SBRT between 10/2004-12/2014. The median prescription dose was 50 Gy in 3 fractions (range 24-64 Gy in 1-10) to the PTV. Patient, tumor and treatment factors and clinical outcomes were extracted from the database. Local recurrence (LR), regional recurrence (RR), distant metastasis (DM), overall (OS) and cause-specific survival (CSS) were calculated from SBRT completion using the Kaplan-Meier method. Univariate analyses were performed using the Cox proportional hazards model. Student’s unpaired t-test and Pearson chi-square/Fisher’s Exact test were used to compare continuous and categorical variables between groups, respectively.
Results:
Mean follow-up time was 2.1y (0.02-10.12y) and similar for both groups. 295 tumors were > 3cm (T2) and 993 < 3cm (T1) (mean size 3.98 v 1.91cm (0.5-9.6cm), p<0.001). There were no statistically significant differences between groups for gender, pulmonary function (median FEV1 1.7 L (56-60% predicted); DLCO 10 ml/min/mmHg (50-51% predicted), medical inoperability (89%), PET (94%) or any invasive mediastinal staging (6%). T1 patients were slightly younger (73.5y T1 v 76.0y T2, p<0.01) and had mildly better ECOG (80% 0-1 T1 v 71% 0-1 T2, p=0.001). T2 tumors were more often biopsied (74% T2 v 63% T1, p<0.001), less often non-squamous (74% v 83%, p=0.002), had higher SUVmax (10.3 T2 v 6.4 T1, p<0.001), more often central (0236) (19% T2 v 11% T1, p=0.001) and treated to a median prescription dose of 53.8Gy T2 v 52.2Gy T1, p<0.001. 3% received chemotherapy (T1 2.6% v T2 4.4%, p=0.11). Although LR was similar between groups, large tumors had a higher risk of RR, DM and death (Table 1). On univariate analysis, LR was predicted by multiple BED parameters (p<0.001), baseline SUVmax (p=0.003) and squamous histology (p=0.012); RR was higher for lower lobe tumors (p=0.008); DM (p=0.006) was higher while OS and CSS lower for central tumors (p=0.03, 0.01).Clinical Outcome Tumor < 3 cm Tumor > 3 cm p-value Local recurrence 3y 7% 11% 0.13 5y 11% 13% Regional Recurrence 3y 9% 13% 0.006 5y 11% 24% Distant Metastasis 3y 11% 16% <0.001 5y 16% 18% Cause-Specific Survival 3y 88% 73% <0.001 5y 81% 66% Overall Survival 3y 61% 45% <0.001 5y 42% 28%
Conclusion:
Large tumors had a higher risk of RR, DM and death after SBRT. These data have implications for consideration and study of pre-SBRT invasive nodal staging and/or systemic therapy in this population. OS and CSS were lower for central tumors warranting further analysis.
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ORAL19.03 - NRG Oncology/RTOG 0813 Trial of Stereotactic Body Radiotherapy (SBRT) for Central Tumors - Adverse Events (ID 1458)
11:07 - 11:18 | Author(s): A. Bezjak, R. Paulus, L. Gaspar, R.D. Timmerman, W.L. Straube, W.F. Ryan, Y. Garces, A.T. Pu, A.K. Singh, G.M.M. Videtic, M. Suntharalingam, P. Iyengar, J.R. Pantarotto, E.A. Levine, A.Y. Sun, M.E. Daly, I. Grills, P.W. Sperduto, D.P. Normolle, J.D. Bradley, H. Choy
- 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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ORAL19.04 - Discussant for ORAL19.01, ORAL19.02, ORAL19.03 (ID 3337)
11:18 - 11:28 | Author(s): F. Mornex
- Abstract
- Presentation
Abstract not provided
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ORAL19.05 - Japanese Multicenter Study of Stereotactic Body Radiotherapy for 661 Medically Operable Patients with Stage I Non-Small Cell Lung Cancer (ID 2835)
11:28 - 11:39 | Author(s): T. Komiyama, H. Onishi, Y. Shioyama, Y. Matsumoto, K. Takayama, Y. Matsuo, A. Miyakawa, H. Yamashita, K. Nihei, H. Matsushita, M. Aoki, T. Kimura, H. Ishiyama, N. Murakami, K. Nakata, A. Takeda, T. Uno, T. Nomiya
- Abstract
- Presentation
Background:
In Japan, stereotactic body radiotherapy (SBRT) has been actively used as a curative treatment option for patients with early stage primary lung cancer. We organized a multi-institutional SBRT study group in Japanese Radiological Society (JRS-SBRTSG) and conducted retrospective study of SBRT for stage I non-small cell lung cancer (NSCLC).. The purpose of this study was to evaluate the treatment outcomes of SBRT for medically operable patients with stage I NSCLC of JRS-SBRTSG.
Methods:
This is a retrospective analysis to review 661 patients (median age, 75 years; male 424, female 237) with stage I (IA 506, IB 155) NSCLC treated in 20 institutions of JRS-SBRTSG. Histology was proven in 486 patients (adenocarcinoma 328, squamous cell carcinoma 117, others 41). A total dose of 32 -70 Gy mainly at the isocenter was prescribed in 4-15fractions. The median calculated biological effective dose (BED) was 107 Gy (range, 64-150 Gy) based on alpha/beta = 10Gy)
Results:
The median follow-up period for all patients was 35 months. Pulmonary complications of NCI-CTC criteria grade > 3 and grade 5 were noted in 1.9% and 0.4% of total patients, respectively. Overall survival rate (OS) at three year (OS-3y) and disease-specific survival rate at three year of total patients was 79% and 89%, respectively. Locally progression free rate at three year was better for T1 (89%) than T2 (80%) but OS-3y was not different in the two subgroups. OS-3y of female patients was much better (93%) than for male patients (72%) (P<0.01). OS-3y was better for BED ³100 Gy subgroup (80%) than BED<100 Gy subgroup (70%). OS-3y of patients accompanying pulmonary interstitial change (n=54) was much worse (42%) than the others. According to multivariate analysis, only of male and presence of pulmonary interstitial change were worse survival factor.
Conclusion:
The outcomes of SBRT for medically operable patients with stage I NSCLC in Japanese multi-institutional large database were retrospectively analyzed. The local progression-free rate and OS were similar to those of JCOG (Japan Clinical Oncology Group) 0403; a prospective phase II study of SBRT (48 Gy in 4 fractions) for stage IA NSCLC, and the OS was almost comparable to that of surgery for high-aged patients. The subgroup of male and presence of pulmonary interstitial change were worse survival factors. SBRT might be promising as an alternative to surgery for operable stage I NSCLC
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ORAL19.06 - Tumor Location Is Associated with Recurrence Pattern and Survival after SBRT in Early Stage NSCLC Patients (ID 2623)
11:39 - 11:50 | Author(s): B. Stam, H. Peulen, J. Belderbos, M. Guckenberger, F. Mantel, I. Grills, A. Hope, N. O'Connell, J. Sonke
- Abstract
Background:
For NSCLC patients treated with SBRT, we investigated if tumor location is associated with recurrence pattern and overall survival.
Methods:
From 2006-2013 1129 patients with early stage NSCLC were treated with cone beam CT guided SBRT (median 54 Gy in 3 fractions, range 23-64 Gy in 1-10 fractions) in 5 different institutes. 719 patients were analyzed after exclusion of patients with (meta)synchronous tumors (n=185), incomplete scanning data or incomplete follow-up (n=225). An average anatomy was constructed based on 109 patients of the 5 institutes using deformable image registration[1]. Subsequently, all patients were registered to this average anatomy and the corresponding dose distribution was deformed accordingly. Tumor location was defined as a 3D Gaussian distribution (standard deviation 2 cm) at the center of the high dose region. These Gaussian distributions were added to a total and per voxel a mean and standard deviation was determined. Totals were obtained for 5 different groups: local recurrence, regional recurrence, distant metastasis, all recurrent disease combined, deceased as well as their complements. By comparing 2 complimentary groups using Welch’s t-test, locations that were significantly associated (p<0.01) with recurrent disease or with overall survival were identified. Recurrent disease rates and overall survival were calculated using the Kaplan-Meier method.
Results:
With a median follow-up of 19 months, local recurrence occurred in 5% of patients, regional recurrence in 5% and distant metastasis in 9%. 74% of patients were alive and 18% was lost to follow-up. Tumors located medially in the left upper lobe were significantly associated with controlled disease (local, regional, distant and all combined). Figure 1A displays as heatmap: disease control (green), recurrent disease (purple), and the region where the two groups differ significantly (yellow). Tumors located peripherally in the left lower lobe were significantly associated with regional recurrences. Tumors located medially/centrally in the right upper lobe were significantly associated with distant metastases and all recurrent disease combined (local, regional and distant together). Tumors located medially/centrally in the right upper lobe were significantly associated with a decreased overall survival (Figure 1B). Figure 1
Conclusion:
In this group of 719 NSCLC patients treated with SBRT, an average anatomy was utilized to analyze associations of tumor location with treatment outcome. Several regions were identified that were significantly associated with disease recurrence and overall survival. Further investigations in the underlying mechanisms of these associations are warrented. 1.ADMIRE Research 2015, Elekta AB, Stockholm, Sweden
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ORAL19.07 - A Novel Nomogram for Predicting Distant Metastases after Lung Stereotactic Body Radiotherapy for Early Stage Lung Cancer (ID 1270)
11:50 - 12:01 | Author(s): S.C. Oh, K. Chagin, N. Woody, M. Ward, Y. Pham, J. Kittel, G.M.M. Videtic, K. Stephans
- Abstract
- Presentation
Background:
While stereotactic body radiotherapy (SBRT) for early stage non-small cell lung cancer (NSCLC) results in excellent local control, distant metastases (DM) remain the most prevalent form of failure. In this analysis, we develop and internally validate a nomogram to predict DM following SBRT for NSCLC.
Methods:
We queried our institutional registry of patients treated with lung SBRT over the past decade (2003-2014) and identified 729 patients with early stage NSCLC eligible for analysis. All patients were treated with definitive intent. Initial patient and tumor variables predicting the likelihood of developing distant metastases were identified from a multivariable Cox proportional hazard model. A nomogram was developed from the initial model using 16 candidate variables and was reduced to the find the best fitting parsimonious model. The nomogram was then internally validated using a 1000 bootstrap resampling process. Accuracy of the nomogram was measured using c-statistics.
Results:
The median follow up was 15.2 months. 157 patients (22%) developed DM at a median time of 10.3 (range 0.2-68.4) months. The median time to death after development of DM was 4.5 months. Sites of DM included lung (113/157 patients), bone (36/157 patients), liver (27/157 patients), brain (25/157 patients), adrenal (8/157 patients), and other (7/157 patients). Age at start of radiotherapy (p = 0.051), tumor size (p = 0.009), PET SUV (p = 0.026), and the presence of synchronous primaries (p = 0.048) were all predictive of DM on multivariable analysis. Using seven patient and tumor variables (Age, BMI, Charlson Comorbidity Index, Tumor Size, PET SUV, Medical Operability, and Presence of a synchronous primary NSCLC), our nomogram successfully predicted distant metastasis and has an internally validated c-statistic of 0.606 (95% CI: 0.563, 0.648). Internal validation with bootstrapping demonstrated persistent validity of the nomogram in predicting distant metastases. Figure 1
Conclusion:
This novel internally validated nomogram can predict the risk of distant metastases in early stage NSCLC treated with SBRT. External validation of this nomogram is warranted. This nomogram may help define subgroups for stratification in future clinical trials and identify patients who may benefit from adjuvant systemic therapies following lung SBRT.
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ORAL19.08 - Discussant for ORAL19.05, ORAL19.06, ORAL19.07 (ID 3561)
12:01 - 12:11 | Author(s): B. Kavanagh
- Abstract
- Presentation
Abstract not provided
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