Journal Thoracic Oncology

Abstracts Journal of Thoracic Oncology • Volume 12 Issue S1 January 2017
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: 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.
Keywords: pemetrexed, Radiotherapy, quality assurance
OA24: RADIOTHERAPY OF LUNG CANCER: RECENT DEVELOPMENTS
WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45
OA24.02 LOCALLY ADVANCED NON-SMALL CELL LUNG CANCER:
RADIOTHERAPY WITH ADAPTIVE STRATEGY (LARTIA TRIAL)
Sara Ramella 1 , Michele Fiore 2 , Sonia Silipigni 2 , Massimo Jaus 3 , Maria Cristina
Zappa 3 , Antonio Alberti 3 , Paolo Matteucci 2 , Elisabetta Molfese 2 , Patrizia
Cornacchione 2 , Lucio Trodella 2 , Edy Ippolito 2 , Rolando D’Angelillo 2
1 Radiation Oncology, Campus Bio-Medico University, Rome/Italy, 2 Campus Bio-
Medico University, Rome/Italy, 3 Sandro Pertini Hospital, Rome/Italy
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 postreplanning),
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: (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.
Keywords: Locally advanced NSCLC, chemoradiation, adaptive radiotherapy
OA24: RADIOTHERAPY OF LUNG CANCER: RECENT DEVELOPMENTS
WEDNESDAY, DECEMBER 7, 2016 - 14:15-15:45
OA24.03 CARDIAC TOXICITY AFTER RADIATION FOR STAGE
III NSCLC: POOLED ANALYSIS OF DOSE-ESCALATION TRIALS
DELIVERING 70-90 GY
Kyle Wang 1 , Michael Eblan 1 , Matthew Lipner 1 , Allison Deal 2 , Timothy Zagar 1 ,
Carrie Lee 3 , Brian Jensen 1 , Panayiotis Mavroidis 1 , Julian Rosenman 1 , Thomas
Stinchcombe 3 , Lawrence Marks 1
1 Radiation Oncology, University of North Carolina Hospitals, Chapel Hill/NC/United
States of America, 2 Biostatistics, University of North Carolina Hospitals, Chapel
Hill/NC/United States of America, 3 Medical Oncology, University of North Carolina
Hospitals, Chapel Hill/NC/United States of America
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 doseescalation
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