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T. Schytte
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MINI 07 - ChemoRT and Translational Science (ID 110)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:D. Raben, B. Kavanagh
- Coordinates: 9/07/2015, 16:45 - 18:15, 201+203
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MINI07.06 - Pattern of Loco-Regional Failure after Definitive Chemo Radiotherapy for NSCLC. Results from NARLAL, a Phase II Randomized Trial (ID 1042)
16:45 - 18:15 | Author(s): T. Schytte
- Abstract
- Presentation
Background:
Concurrent chemo-radiotherapy (CRT) is the treatment of choice in loco-regional advanced non-small cell lung cancer (LA-NSCLC). Even though the patients are treated with curative intend the loco-regional control at 2 year is only about 30% in clinical trials. The aim of this study is to compare the loco-regional failure in patients treated with 66 Gy vs 60 Gy in the randomized phase II trial, NARLAL. Furthermore to analyze the localization of relapse compared to the original treatment plan.
Methods:
From 2009-2013 117 patients with LA-NSCLC were randomized in a national multicentre protocol between 60 Gy/ 30 F (arm A) and 66 Gy/ 33 F (Arm B), 5 FW. Navelbine[®] 50 mg 3 days a week was given as concomitant regimen. Patients were followed with CT scans every 3[rd] month in 2 years and hereafter every 6[th] month for another 3 years. As part of the protocol a PET-CT scan was performed 9 months after randomization. In case recurrent disease was suspected a biopsy was done from the lesion if possible. The recurrence gross tumor volume will be delineated and registered with the original radiation treatment plan to identify the site of failure.
Results:
Fifty-nine patients were treated in arm A and 58 patients in arm B. The median local recurrence free interval was 10 months in arm A and 10.9 months in arm B (p=0.57). At the end of this analysis 22 patients were alive with no evidence of loco-regional disease, 16 patients had died with no evidence of loco-regional failure. Loco-regional failure in high-dose area was diagnosed in 60 (51%) patients (33 patients in arm A and 27 patients in arm B). Loco-regional failure outside high-dose area was diagnosed in 19 patients. Fig 1. Treatment plan 60 Gy/ 30 F and PET-CT with relapse (verified by biopsy) Figure 1
Conclusion:
Although this treatment was with curative intend, the loco-regional control was disappointingly poor in both treatment arms. This is in line with other newly published clinical dose-escalations trials for NSCLC. In order to improve loco-regional control and hopefully survival homogeneous dose-escalation is not the choice. Inhomogenous dose-escalation may be an alternative. A phase III trial on this subject has just started enrolment in Denmark (NARLAL II, www.clinicaltrials.gov). Acknowledgements Supported by CIRRO- The Lundbeck Foundation Center for Interventional Research in Radiation Oncology.
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ORAL 36 - Translational Science/Radiation (ID 151)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:E. Vokes, B. Kavanagh
- Coordinates: 9/09/2015, 16:45 - 18:15, Mile High Ballroom 2c-3c
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ORAL36.07 - Results of a National Test Run of Treatment Plans for the Standard Arm of a Dose Escalation Trial for Locally Advanced NSCLC (ID 1766)
16:45 - 18:15 | Author(s): T. Schytte
- Abstract
- Presentation
Background:
A national quality assurance program was conducted in order to compare standard radiation treatment plans for locally advanced non-small cell lung cancer (NSCLC) patients in Denmark.
Methods:
The five participating centres represented 71% of all radiotherapy centres in Denmark. They were provided with the CT images and delineations of GTV, CTV, PTV and organs at risks for five different NSCLC patients. Each centre created treatment plans based on the following optimization objectives: required dose distribution for target coverage 95%-107% of the prescribed dose of 66Gy/33fr to at least 95% of the PTV volume (90% for volume located in lung tissue); constraints for organs at risks D(max) < 50Gy to the spinal cord, D(max) < 70Gy to the oesophagus, V50 < 20% to the heart, V20 < 35% and D(mean) < 20Gy for the total lung volume (excluding the GTV). The treatment planning was done in accordance with the local centre practice; i.e. choice of IMRT versus VMAT, coplanar vs. non-coplanar technique, feasible functionalities for treatment planning optimisation (mean value versus different points at the DVH curve), and any additional local dose constraints (e.g. D(max) < 45Gy to spinal cord and/or V5 < 60% to the total lung volume). Finally, all treatment plans were collected and analysed cooperatively.
Results:
All objectives for target coverage and organs at risk were met. There was a wide variability in the dose volume histograms (DVHs) for some of the organs at risk, especially the lungs. This is illustrated in the figure, where the lung DVH from seven different treatment plans, created for the same patient by the five participating centres, is shown. The lung DVHs are overlapping around 20Gy, as all centres had a dose constraint on V20. Some centres had an additional local dose constraint on V5, which resulted in decreased doses to the lungs and increased doses to the mediastinal structures compared with centres that had no dose constraints on V5 for the lungs. Figure 1
Conclusion:
Differences in the dose distribution to the organs at risk can have an impact on treatment morbidity (e.g. pneumonitis, oesophagitis). These differences were seen for standard treatment plans, which are often used in multicentre clinical trials as the baseline compared to an experimental arm, where such differences can be even more pronounced. It is highly recommended to perform test runs across centres prior to entering clinical trials in order to uncover differences as the ones presented.
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P1.02 - Poster Session/ Treatment of Localized Disease – NSCLC (ID 209)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.02-038 - A Comparison of Stereotactic Body Radiation Therapy vs. No Treatment for Patients with Early-Stage Non-Small Cell Lung Cancer (ID 1449)
09:30 - 17:00 | Author(s): T. Schytte
- Abstract
Background:
Scarce information is available concerning the natural history of untreated patients with early-stage Non-Small Cell Lung Cancer (NSCLC). No randomized studies have been conducted comparing Stereotactic Body Radiation Therapy (SBRT) with no treatment for patients with early-stage NSCLC. Previously, it has been suggested that SBRT increases overall survival for patients with NSCLC T1-2N0M0. In this study a national group of untreated patients with early-stage NSCLC was identified in order to compare the effect of SBRT with the natural history in a retrospective setting.
Methods:
From 2007 to 2013, 136 patients diagnosed NSCLC T1-2N0M0 with a tumor diameter up to 5 cm were treated with SBRT at Odense University Hospital. The thoracic RT consisted of 45-66 Gy/3 F delivered in 9 days. For the same period, a national group of 121 untreated patients with early-stage NSCLC was extracted from the Danish Lung Cancer Registry. Of these, 85 patients survived more than one month after the diagnosis was established and might have been candiates to SBRT. Twenty-four patients with unrecorded tumor diameter were excluded from the present analysis thus, 61 patients remained in the untreated group. Pathoanatomical diagnosis was known for all patients. Kaplan-Meier and Cox proportional hazard analyses were used for uni- and multivariable survival analyses, respectively. Overall survival (OS) was calculated from the date of diagnosis.
Results:
The mean age was 72 vs. 78 years in the SBRT and untreated group, respectively. Statistically significant (p<0.05) inter-group differences in patient characteristics were observed for pathological type and FEV1 (%predicted). No difference in gender, tumor size, ECOG performance status, or pack years was observed. The potential median follow-up time was 38 months in the SBRT group vs. 57 months among untreated. A log rank test showed a significant difference of overall survival (OS) between groups e.g. resulting in an OS at 5-year of 44% vs. 10% respectively and a median OS of 47.8 vs. 12.2 months for SBRT and untreated group, respectively (p < 0.01). Multivariate analysis indicated that age, tumor size, pack years, gender, adenocarcinoma and FEV1 (%predicted) had no significant influence on survival, while SBRT and ECOG performance status had (Table 1). Figure 1
Conclusion:
In this study SBRT was associated with significantly longer OS compared to no treatment, suggesting that SBRT is a convenient treatment that increases survival for patients with early-stage NSCLC.
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P1.02-039 - Stereotactic Radiotherapy as Salvage Treatment after Stereotactic Radiotherapy or after Operated Non-Small-Cell Lung Cancer (ID 2240)
09:30 - 17:00 | Author(s): T. Schytte
- Abstract
Background:
Lobectomy is regarded as the standard of care for early stage non-small-cell lung cancer (NSCLC), but stereotactic radiotherapy (SBRT) is an option for patients who are not candidates for surgery. Although the curative intention treatments, a significant proportion of patients with NSCLC will develop recurrent disease. For patients previously treated with SBRT little is known of retreatment with SBRT in the recurrent setting.
Methods:
All patients with lung cancer treated at our center with SBRT have been registered prospectively. We identified the patients who had salvage SBRT after prior pulmonary surgery or SBRT. Overall survival was calculated from the day of salvage SBRT.
Results:
Between November 2008 and February 2015, 198 patients were treated with SBRT. We identified 24 patients that had received SBRT as salvage treatment for their first recurrence in the lung. Surgery was the initial treatment for 13 of the patients (OP-group) and SBRT was the initial treatment for the remaining 11 patients (RT-group). By the end of follow up, 5 patients in the OP-group had died and 3 in the RT-group. In the OP-group all the salvage SBRT was given as 66 Gy in 3 fractions. In the SB-group, 5 was treated with 56 Gy in 8 fractions, 1 with 45 Gy in 3 fraction and 1 with 45 Gy in 10 fractions when given salvage SBRT.Primary surgery Primary SBRT All Number of patients 13 11 24 Age mean (range) 75 (62-88) 69 (53-87) 72 (53-88) Histology Plano/Adeno/NOS 3/8/2 4/5/2 7/13/4 Time in months from primary treatment to salvage SBRT median (range) 65 (4-236) 17 (5-44) 21 (4-236) Survival time from SBRT 1 year (%) 2 year (%) 85 62 89 61 87 60 Median follow-up months (range) 27.6 (14.3-62.8) 15.9 (1.4-32.9) 21 (1.4-62.9) Lung function FEV1, median (range 1.4 (0.6-2.7) 1.4 (0.4-2.8) 1.4 (0.4-2.8) ECOG Performance Status 0 1 2 3 4 5 3 1 1 2 7 1 5 7 10 2
Conclusion:
Although the time from primary treatment to salvage SBRT was longer if surgery was the primary treatment than if the primary treatment was SBRT, the overall survival was equal for the two groups.
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P2.07 - Poster Session/ Small Cell Lung Cancer (ID 222)
- Event: WCLC 2015
- Type: Poster
- Track: Small Cell Lung Cancer
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.07-015 - Pattern of Failure after Definitive Radiotherapy for Small Cell Lung Cancer (ID 2423)
09:30 - 17:00 | Author(s): T. Schytte
- Abstract
Background:
The standard of care for limited disease SCLC is chemo-radiotherapy. The recommended radiotherapy schedule is 45 Gy/30 F bi-daily (BD-RT) for patients in good performance status according to various guidelines. However, a large proportion of these patients are not able to fulfill the bi-daily schedule due to frailty. For these patients 45 Gy/25 F, once-daily (OD-RT) has been the standard of care at our institution. The aim of this study was to investigate the pattern of failure and survival after chemo-radiotherapy with the 2 different radiotherapy schedules.
Methods:
Records of 106 patients with limited disease SCLC treated from 2007 to 2013 with definitive chemo-radiotherapy in our institution were reviewed. The chemotherapy regimen was a platinum doublet with etoposide. The radiotherapy schedule for 69 patients was treatment OD-RT (45 Gy/25 F), whereas 37 patients were treated BD-RT (45 Gy/30 F). Log rank tests were used to compare overall survival (OS) and local failure free survival (LFS) between the groups.
Results:
In the OD-RT 23 patients (33%) were either alive or dead without evidence of recurrence, and 15 patients (41%) in the BD-RT. In the OD-RT 21 patients (30%) had locoregional recurrence only, 12 patients (17%) had locoregional and distant relapse, and 13 patients (19%) had distant metastasis only. In the BD-RT 8 patients (22%) had locoregional recurrence only, 8 patients (22%) had locoregional and distant failure, and 6 patients (16%) had distant relapse only. Statistically significant (p<0,05) differences in patient characteristics between the two groups were observed: fraction of Performance Status 0-1 93% vs 67%, fraction treated with PCI 78% vs 54% and mean age of 62 vs 67 years for the groups BD-RT and OD-RT respectively. No differences were observed in S-sodium, LDH or gender. The mean follow-up was 24 months. Median overall survival was 18 months in OD-RT and 24 months in BD-RT, and 2 year OS was 45% vs 43% respectively (p=0.23). Median local-failure free survival was 13 months in OD-RT vs 33 months in BD-RT, and 2 year LFS was 57% vs 40% respectively (p=0.19) Local failure free survuval: Figure 1
Conclusion:
In this study the locoregional control and overall survival was not significantly better in the bi-daily regimen with 45 Gy/30 F compared to once-daily treatment with 45 Gy/25 F. This was unexpected, because the two groups differed significantly in PS, PCI and age in favour of the bi-daily regimen. But the size sample was small and follow-up time short.
