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K. Dieckmann
Moderator of
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IA04 - Interactive Session Target Delineation: Group I (Ticketed Session) (ID 290)
- Event: WCLC 2016
- Type: Interactive Session
- Track: Radiotherapy
- Presentations: 1
- Moderators:K. Dieckmann, H. Prosch
- Coordinates: 12/05/2016, 16:00 - 17:30, Schubert 3
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IA04.01 - Interactive Session Target Delineation (ID 6521)
16:00 - 17:00 | Author(s): C. Faivre-Finn, L. Gaspar, B. Loo
- Abstract
- Presentation
Abstract not provided
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IA06 - Interactive Session Staging Group II (Ticketed Session) (ID 292)
- Event: WCLC 2016
- Type: Interactive Session
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:K. Dieckmann, H. Prosch
- Coordinates: 12/06/2016, 11:00 - 12:30, Schubert 3
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IA06.01 - Interactive Session Staging (ID 6520)
11:00 - 12:30 | Author(s): E. Stiefsohn, L. Havel, A. Kerpel-Fronius
- Abstract
Abstract not provided
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IA07 - Interactive Session Target Delineation: Group II (Ticketed Session) (ID 293)
- Event: WCLC 2016
- Type: Interactive Session
- Track: Radiotherapy
- Presentations: 1
- Moderators:K. Dieckmann, H. Prosch
- Coordinates: 12/06/2016, 16:00 - 17:30, Schubert 3
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IA07.01 - Interactive Session Target Delineation (ID 6522)
16:00 - 17:30 | Author(s): C. Faivre-Finn, B. Loo
- Abstract
- Presentation
Abstract not provided
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OA24 - Radiotherapy of Lung Cancer: Recent Developments (ID 411)
- Event: WCLC 2016
- Type: Oral Session
- Track: Radiotherapy
- Presentations: 8
- Moderators:K. Dieckmann, S. Rieken
- Coordinates: 12/07/2016, 14:20 - 15:50, Stolz 1
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OA24.01 - Radiotherapy Quality Assurance of Concurrent Chemoradiotherapy in PROCLAIM Phase III Trial (ID 4274)
14:20 - 14:30 | Author(s): A.M. Brade, F. Wenz, F. Koppe, Y. Lievens, B. San Antonio, N.A. Iscoe, A. Hossain, N. Chouaki, S. Senan
- Abstract
- Presentation
Background:
Trials of chemoradiotherapy for different tumors, including lung cancer, have shown a correlation between protocol deviations and adverse outcomes. Radiation quality assurance (RTQA) was mandated for all patients treated in the PROCLAIM (NCT00686959) trial evaluating two different chemoradiotherapy regimens.
Methods:
The study was open to accrual between 2008-2012. Planned chemoradiotherapy dose was 60-66 Gy in daily 2 Gy fractions. Quality was assessed through review of radiation treatment plans and monitoring of protocol violations. Review of the radiation plan was mandated for all patients; prior to radiation start for the first enrolled patient at each site. Real-time review was performed randomly in 20% of additional patients with nonreal-time review performed for the remainder. Parameters assessed for major violations per protocol included: <95% of planned total volume (PTV) received by 93% of prescribed dose; >1 cm[3] contiguous volume within or outside the PTV received >115% of prescribed dose; V~20~ (volume of lung receiving ≥20 Gy) >38%; and maximum point dose to spinal cord of >48 Gy. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kapan-Meier methodology and groups were compared by log-rank test and Cox proportional hazard modeling.
Results:
Of 598 patients randomized in 126 investigational sites, 554 received study assigned chemoradiotherapy. The median dose delivered was 66 Gy, with 92.6% of patients receiving planned chemoradiotherapy dose (60-66 Gy). A total of 40 patients, enrolled at twenty-eight sites had major RTQA violations. Seven sites enrolled ≥2 patients with major violations. Patients with major violations has a higher incidence of Stage IIIB disease (70.0% vs. 50.6%) and larger tumors (median planned PTV=653 vs. 523cc) than patients with no violations. Patients treated at sites with ≥2 patients with violations (n=86), had a lower median OS (median 21.1 vs. 29.8 months; HR 1.442) and median PFS (median 7.3 vs. 11.3 months; HR 1.345) than patients at sites where none had violations.
Conclusion:
Major chemoradiotherapy protocol violations were uncommon in the PROCLAIM study, which may be a reflection of the mandatory RTQA. Protocol violations were more frequent in patients with Stage IIIB and larger tumors, which generally require more complex chemoradiotherapy plans. The observation of discrepant outcomes at centres with multiple major RTQA violations is hypothesis-generating but should be interpreted with caution due to the small number of patients.
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OA24.02 - Locally Advanced Non-Small Cell Lung Cancer: RadioTherapy with Adaptive Strategy (LARTIA Trial) (ID 6161)
14:30 - 14:40 | Author(s): S. Ramella, M. Fiore, S. Silipigni, M. Jaus, M.C. Zappa, A.M. Alberti, P. Matteucci, E. Molfese, P. Cornacchione, L. Trodella, E. Ippolito, R.M. D'Angelillo
- Abstract
- Presentation
Background:
Anatomical change of tumor contour during radiotherapy contributes to target missing. Adaptation of tumor volume could however result in an increased incidence of recurrences in the area of target reduction. This study aims to investigate the incidence of failure of adaptive approach in evaluating the risk of local recurrence in the area excluded during replanning.
Methods:
In this prospective study, LA-NSCLC patients treated with concomitant chemoradiation underwent weekly chest-CT simulation during therapy. In case of tumor shrinkage, a new tumor volume (TV) was delineated and a new treatment plan outlined (replanning). Patterns of failure were classified as: in field (persistence or recurrence in TV post-replanning), marginal (recurrence in the area of initial TV excluded from the post-replanning TV) and out of field (recurrence outside of initial TV). Toxicity, OS, and PFS were reported.
Results:
A total of 217 NSCLC patients were treated in our centre from 2012 to 2014. In 50 cases a target volume reduction was recorded and replanning outlined. A mean initial and replanning CTV of 154.9cc and 90.7cc were reported with an average CTV shrinkage of 42% between simulation CT and replanning CT. With a median follow-up of 20.5 months, 30% of patients experienced local failure which was in field, marginal and out of filed in 20%, 6% and 4% of cases respectively. Acute G3 pulmonary and esophageal toxicity was reported in 2% and 4% of patients respectively. Figure 1 Figure 1: (A) Tumor volume delineation at first CT simulation; (B) the reduced target volume at replanning CT
Conclusion:
The possibility to reduce toxicity and the documented low rate of marginal failures makes the adaptive approach a modern option for future randomized studies. The best scenario to confirm tumor activity is its application in neoadjuvant chemoradiation trials.
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OA24.03 - Cardiac Toxicity after Radiation for Stage III NSCLC: Pooled Analysis of Dose-Escalation Trials Delivering 70-90 Gy (ID 4322)
14:40 - 14:50 | Author(s): K. Wang, M.J. Eblan, M. Lipner, A.M. Deal, T.M. Zagar, C.B. Lee, B.C. Jensen, P. Mavroidis, J.G. Rosenman, T.E. Stinchcombe, L.B. Marks
- Abstract
- Presentation
Background:
Radiation (RT) associated cardiac injury in patients with lung cancer is of unclear significance. RTOG 0617 demonstrated reduced overall survival (OS) with dose-escalated RT for Stage III NSCLC, with higher heart doses predicting for worse OS. We assessed the impact of heart doses on toxicity and survival for patients enrolled on several prospective RT dose-escalation trials.
Methods:
From 1996-2009, 133 patients with Stage III NSCLC (ECOG PS 0-1) were treated on six prospective trials using induction/concurrent chemotherapy and dose-escalated conformal RT to 70-90 Gy. Broad clinical outcomes (e.g. OS) were prospectively assessed. RT plans were reviewed, cardiac structures were defined, and dose/volume metrics were computed. Patient records were retrospectively reviewed for post-RT symptomatic cardiac events (symptomatic pericardial effusion, acute coronary syndrome, and pericarditis). Baseline cardiac risk was calculated using the World Health Organization / International Society of Hypertension (WHO/ISH) score. A competing risks model accounting for the risk of death was used for statistical analysis.
Results:
112 patients were included in the final analysis. Median f/u was 19 mo. (75 mo. for the 39 patients without documented progression). Median OS and PFS were 22 and 12 mo. Median prescribed RT dose was 74 Gy. 15 patients (13%) had symptomatic cardiac events (6 pericardial effusion, 5 myocardial infarction, 2 unstable angina, 2 pericarditis) at median 26 mo. post-RT (range, 7-68). On univariate analysis, Heart mean dose (p=0.001), Heart V5Gy (p<0.001), and Heart V30Gy (p=0.002) were associated with symptomatic cardiac events, whereas baseline WHO/ISH score (p=0.204) and coronary artery disease (p=0.109) were not. Heart doses were higher in patients with vs without events (mean 22Gy vs 11Gy, V5Gy 60% vs 35%, V30Gy 35% vs 14%). On multivariate pair analysis accounting for baseline risk, heart doses remained significant predictors of cardiac events (e.g. Heart mean dose, p=0.001, HR 1.05 / 1Gy). 2-year competing risk-adjusted rate of symptomatic cardiac events was 11.1% vs 1.5% for Heart mean dose ≥15Gy vs <15Gy (p=0.003, HR 6.7). 34 patients (30%) had asymptomatic pericardial effusions. There was no association between heart doses and OS.
Conclusion:
Clinically significant symptomatic cardiac events following high-dose thoracic RT for Stage III NSCLC occurred in 13% of patients at a median 2 years post-RT, with the rate appearing to be heart dose dependent. RT-associated cardiac toxicity in the definitive treatment of Stage III NSCLC may occur earlier than historically understood, and heart doses should be minimized. Supported in part by NIH grant CA69579.
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OA24.04 - Discussant for OA24.01, OA24.02, OA24.03 (ID 7005)
14:50 - 15:05 | Author(s): F. McDonald
- Abstract
- Presentation
Abstract not provided
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OA24.05 - The Nordic HILUS-Trial - First Report of a Phase II Trial of SBRT of Centrally Located Lung Tumors (ID 6140)
15:05 - 15:15 | Author(s): K. Lindberg, P. Bergström, O.T. Brustugun, S. Engelholm, V. Grozman, M. Hoyer, K. Karlsson, A. Khalil, C. Kristiansen, I. Lax, B. Löden, J. Nyman, G.F. Persson, L. Rogg, P. Wersäll, R. Lewensohn
- Abstract
- Presentation
Background:
Early attempts of stereotactic body radiation therapy (SBRT) of centrally located lung tumors resulted in high toxicity, questioning the utility of the method in this situation. Since then, different risk adapted fractionation schedules with acceptable toxic effects have been reported from various institutions. However, consensus on the tolerability of centrally located structures to high-fraction doses is still lacking and the clinical toxic effects in relation to dose to organs at risk (OAR) need to be evaluated.
Methods:
We here report a first toxicity analysis of the HILUS-trial – a prospective Nordic multicenter non-randomized phase II trial of SBRT to centrally located lung tumors. Patients with a centrally located tumor (defined as ≤1cm from the proximal bronchial tree) from either a primary non-small cell lung cancer (NSCLC) or a progressive metastasis from another solid tumor were eligible for the trial. Maximum tumor diameter was 5 cm. Patients receiving concomitant systemic anticancer therapy or with tumors reaching through the wall of a main bronchus were not eligible. All the patients were treated with 7Gyx8 and stratified to either arm A (=tumors close to a main bronchus) or arm B (=tumors close to a lobar bronchus). The aim was to include 30 patients in each arm. Follow-up was conducted every 3[rd] month during the first 2 years and thereafter every 6[th] month. The trial was approved by ethical committees in each country.
Results:
Seventy-four patients (42 in arm A and 31 in arm B) were included between 2011 and 2016. Sixty-five patients experienced side effects from the study treatment; the most common being grade 1-2 dyspnea, grade 1-2 cough and grade 1-2 fatigue. Twenty-one patients (28%) experienced grade 3-5 side effects (atrioventricular block, bleeding, dyspnea, empyema, fatigue, fever, fistula, lung infection, pain, pneumonitis, pneumothorax and ventricular arrhythmia). Seven patients (6 in group A and 1 in group B) may have suffered grade 5 side effects; six patients experienced lethal hemoptysis after a median of 15.5 months (2.5-21months) and one patient suffered from a lethal pneumonitis 5 months post study treatment. Grade 4-5 side effects occurred more frequently in group A than in group B (19% vs 3%). Further analyses of risk factors for serious toxicity in relation to dose-volume parameters and patient- and tumor characteristics will be presented.
Conclusion:
SBRT of centrally located tumors may be afflicted with high risk of serious toxicity and further evaluation of clinical and dose-volume dependent risk factors are highly warranted.
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OA24.06 - Histologic Subtype of Early-Stage Lung Adenocarcinoma is a Predictor of Failure Patterns after Stereotactic Body Radiation Therapy (ID 4618)
15:15 - 15:25 | Author(s): J.E. Leeman, A. Rimner, J. Montecalvo, M. Hsu, Z. Zhang, D. Von Reibnitz, K. Panchoo, E. Yorke, P.S. Adusumilli, W.D. Travis, A.J. Wu
- Abstract
- Presentation
Background:
Stereotactic body radiation therapy (SBRT) has emerged as an effective treatment for early-stage lung cancer. Histologic subtyping in surgically resected lung adenocarcinomas is recognized as a prognostic factor, with the presence of solid or micropapillary patterns predicting poor outcomes. Herein, we describe outcomes following SBRT for early-stage lung adenocarcinoma by histologic subtype.
Methods:
We identified 119 consecutive patients (124 lesions) with stage I-IIA lung adenocarcinoma who were treated with definitive SBRT at our institution between August 2008 and August 2015 and had undergone core biopsy. Histologic subtyping was performed according to the 2015 WHO Classification. Thirty-seven tumors (30%) were of high risk subtype, defined as containing a component of solid and/or micropapillary pattern. Cumulative incidences of local, nodal, regional and distant failure were compared between high risk vs. non-high risk adenocarcinoma subtypes with Gray’s test, and multivariable-adjusted hazard ratios were estimated from propensity score-weighted Cox regression models.
Results:
Median follow-up for the entire cohort was 17 months and 21 months for surviving patients. The 1-year cumulative incidence of local, nodal, regional and distant failure, respectively, in high risk and non-high risk lesions were 7.3%, 14.8%, 4.0%, 22.7% and 2.7%, 2.6%, 1.2%, 3.6%. Hazard ratios for local, nodal, regional and distant failure, respectively, of high risk lesions compared to non-high risk were 16.8 (95% CI 3.5-81.4), 3.8 (95% CI 0.95-15.0), 20.9 (95% CI 2.3-192.3), 6.9 (95% CI 2.2-21.1). No significant difference was seen with regard to overall survival.
Conclusion:
Outcomes following SBRT for early-stage adenocarcinoma of the lung are highly correlated with histologic subtype, with micropapillary and solid tumors portending significantly higher rates of locoregional and metastatic progression. In this context, histologic subtype based on core biopsies is a novel prognostic factor and may have important implications for patient selection, adjuvant treatment, biopsy methods and clinical trial design.
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OA24.07 - The Impact of Population Heterogeneity on the Efficacy of SBRT to the Lung (ID 6186)
15:25 - 15:35 | Author(s): N. Woody, C.A. Reddy, M.E. Abazeed
- Abstract
- Presentation
Background:
Stereotactic Body Radiation Therapy (SBRT) is the standard of care for medically inoperable patients with early-stage non-small cell lung cancer (NSCLC). However, NSCLC is comprised of several histological subtypes and the impact of this heterogeneity on SBRT treatments has yet to be established.
Methods:
We analyzed 740 early-stage NSCLC patients treated definitively with SBRT from 2003 through 2015. We calculated cumulative incidence curves using the competing risk method and identified predictors of local failure using Fine and Gray regression.
Results:
Overall, 72 patients had a local failure with a cumulative incidence of local failure at three years of 11.8%. On univariate analysis, squamous histology, younger age, fewer medical comorbidities, higher BMI, higher PET SUV, central tumors and lower radiation dose were associated with an increased risk of local failure. On multivariable analysis, squamous histology (HR 2.4 p = 0.008) was the strongest predictor of local failure. Patients with squamous cancers fail SBRT at a significantly higher rate than those with adenocarcinomas or NSCLC-not otherwise specified, with three-year cumulative incidences of local failure of 18.9% (95% CI= 12.7-25.1%), 8.7% (95% CI= 4.6-12.8%), 4.1% (95% CI= 0-9.6%), respectively.
Conclusion:
Our results demonstrate an increased rate of local failure after SBRT in patients with squamous cell carcinoma. Standard approaches for radiotherapy that demonstrate efficacy for a population may not achieve optimal results for individual patients. Establishing the differential dose-responses of SBRT across histological groups is likely to improve efficacy and inform ongoing and future studies that aim to expand indications for SBRT.
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OA24.08 - Discussant for OA24.05, OA24.06, OA24.07 (ID 7105)
15:35 - 15:50 | Author(s): F.(. Kong
- Abstract
- Presentation
Abstract not provided
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Author of
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ED11 - Advanced NSCLC: State-of-the-Art Treatment (ID 280)
- Event: WCLC 2016
- Type: Education Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:C. Manegold, C. Zhou
- Coordinates: 12/07/2016, 11:00 - 12:30, Hall C8
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ED11.04 - Palliative Radiotherapy of Advanced NSCLC (ID 6488)
12:10 - 12:30 | Author(s): K. Dieckmann
- Abstract
- Presentation
Abstract not provided
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P2.02 - Poster Session with Presenters Present (ID 462)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.02-011 - Management of Non-Small-Cell Lung Cancer (NSCLC) Stage III Patients in Central European Countries (ID 4608)
14:30 - 14:30 | Author(s): K. Dieckmann
- Abstract
Background:
The aim of the study is to determine the actual standard management of patients with stage III NSCLC in Central European centres/countries. The project is a multicentre, prospective, non-interventional registry.
Methods:
After ethical committee approval and signed informed consent, the data about diagnostic and therapeutic procedures of consecutive patients diagnosed with stage III NSCLC (UICC7) were collected in web-based registry organised by the IBA MUNI, Brno, Czech Republic.
Results:
With cut-off 30 June 2016, 509 patients from 7 countries/16 centres were enrolled, median number of patients per centre being 23 (range 6-99). There were 163 (32%) women and 37 (7%) never smokers. Performance status distribution was as follows: ECOG 0, 1, 2 and 3 in 29%, 56%, 12% and 3%, respectively. Squamous cancer was found in 52%, adenocarcinoma in 39%, not otherwise specified in 5% and others in 4% of cases. Genetic mutations were examined in 119 (23%) patients, predominantly EGFR in 111 subjects with 10 (8%) positive findings, while the ALK mutation in 64 patients with no positive finding. Regular staging procedures were X-Ray scan (97%), chest CT (96%) and bronchoscopy (89%). Staging was completed by abdominal CT in 66% of patients, abdominal US in 29%, PET/CT in 22%, bone scan in 17% and brain CT or MRI in 13%, respectively. Stage IIIA was found in 59% and stage IIIB in 41% of patients. N2/N3 nodes were diagnosed in 60%/22% of patients. Pathological mediastinal lymph-node positivity was confirmed in 109 (21%) patients (6% EBUS, 0.2% VATS, 1% mediastinoscopy, 1% transbronchial biopsy and 13% surgery). Median time from diagnosis to first treatment was 23 days (range 0–321). Treatment procedures were: surgery 138 (27%), chest radiotherapy 246 (48%) and chemotherapy 409 (80%) of subjects, respectively. Chemotherapy as only modality was given in 136 (27%) of patients. Surgery was combined with radiation in 6 cases, with chemotherapy in 79 (16%) cases and with both chemotherapy and radiotherapy in 37 (7%) patients. Chemotherapy plus radiotherapy was given in 159 (31%) patients including concurrent chemoradiotherapy in 67 (13%) cases. At the time of cut-off, 64% patients were alive, median survival time was not reached, and the 1-year estimated survival rate was 71%.
Conclusion:
The most prevalent histology was squamous cancer. Histopathological examination of mediastinal lymph-nodes was done in 21% of patients, mostly during surgery. Majority of patients (55%) were treated with combination therapy. Palliative chemotherapy only was given in 27% of patients. Survival data are not mature.
