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F. Mornex
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ED 01 - Update in Radiation Oncology (ID 1)
- Event: WCLC 2015
- Type: Education Session
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
- Moderators:W.J. Curran, P. Van Houtte
- Coordinates: 9/07/2015, 14:15 - 15:45, 205+207
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ED01.03 - Post-Operative Radiotherapy for Stage III Disease (ID 1772)
14:15 - 15:45 | Author(s): F. Mornex
- Abstract
- Presentation
Abstract:
Despite advances in treatment, lung cancer remains the leading cause of cancer mortality in most countries. About one third of patients with non-small cell lung cancer (NSCLC) presents with locally advanced non-metastatic disease (stages IIIA and B). Although 5-year overall survival (OS) ranges from 60 to 73% for completely resected pathologic stage I disease, OS decreases to less than 25% for pathological stage III disease. Patients with potentially resectable stage IIIA-N2 can be treated with induction chemotherapy followed by radical surgery. Prospective studies report 5-year OS rates from 20% to 30%, with about 30% of the patients reporting local recurrence (LR). When surgery is performed first, for patients presenting with node-positive disease at the time of resection, meta-analysis data demonstrate that adjuvant platinum-based chemotherapy has been shown to decrease distant metastases and locoregional recurrence (LRR), resulting in an approximately 5% OS advantage, and is now considered standard of care for patients with resected node-positive NSCLC. However, these patients have a 20% to 40% risk of LRR, and LRR correlates independently with worse OS. Thus, postoperative radiotherapy (PORT) holds great appeal as a means to reduce LRR and improve OS. Several phase III trials investigated the role of PORT after surgical resection in NSCLC. In 1998, the PORT Meta-analysis Trialists Group undertook an individual participant data (IPD) meta-analysis (of both published and unpublished trial data) of PORT versus surgery alone in NSCLC [1]. The original meta-analysis, based on 9 randomised controlled trials and 2128 patients, concluded that PORT was detrimental with a 7% absolute reduction in 2-year OS and a 4% reduction in recurrence-free survival. Subgroup analyses suggested that PORT was increasingly detrimental with decreasing stage (p = 0.0003) and lower nodal status (p = 0.016). The updated results for OS, and for local, distant and overall recurrence-free survival are unchanged, continuing to show a detrimental effect of PORT(2) : For the whole patient group, PORT decreased the OS at two years by 6% (52% vs. 58%). This deleterious effect was detected in patients with pN0–1 disease. No effect was detected in patients with pN2 disease. The PORT meta-analysis raised a lot of criticism for the following reasons: significant heterogeneity between trials, inclusion of trials with old radiotherapy techniques (notably, most of these trials, conducted principally in the 1960s to 1970s, included outmoded RT techniques and doses). The deleterious effect of PORT has been attributed to an excess of intercurrent deaths, with a high incidence of cardiac and respiratory complications due to poor radiotherapy techniques. In support of this hypothesis, several more recent trials with contemporary radiation techniques did not report an increase of death from intercurrent disease. Kepka et al. did not detect a difference in QoL scores, cardiopulmonary morbidity or non-cancer related deaths between patients receiving PORT and those treated with surgery alone (3). Two Surveillance, Epidemiology, and End Results (SEER) analyses and a secondary analysis of data from the Adjuvant Navelbine International Trialist Association (ANITA) trial suggest that PORT may be safely delivered in a modern cohort of patients with a potential OS benefit for stage IIIA (N2) disease (4, 5). In addition, being now established that the use of adjuvant chemotherapy in stage III disease prolongs OS, it is then hypothesised that with the reduction of distant metastases with chemotherapy, the survival benefit by improved local control after three-dimensional conformal (3D-CRT) PORT will occur. Then, recently, the National Cancer Data Base (NCDB), joint program of the Commission on Cancer of the American College of Surgeons and the American Cancer Society, has been queried to study the impact of modern PORT in the setting of standard-of-care adjuvant chemotherapy for pathologic stage IIIA (N2) NSCLC (6). Data of 1850 patients who received PORT between 1998 and 2010 were obtained. Use of PORT, compared with no PORT, was associated with a significant increase in median OS (45.2 v 40.7 months, respectively), 3-year OS (59.3% v 55.2% , respectively), and 5-year OS (39.3% v 34.8%, respectively; P=.014. This analysis of the NCDB for patients with pathologic N2 disease, receiving adjuvant chemotherapy, shows that PORT seems to confer an additional improvement in OS. In conclusion, modern radiotherapy techniques should be evaluated in stage III patients, as already stated in the initial individual-patient-data meta-analysis. This new evaluation is justified for several reasons: (a) the N2 population has changed because of a better selection with pre-treatment PET-CT scan and brain imaging; (b) adjuvant chemotherapy has become a standard of care in these patients; (c) technical advances of radiotherapy may enhance the ability of PORT to improve local relapse-free survival and possibly overall survival. Thus, based on the previous studies, the underlying hypotheses remain to be proven, with sufficiently powered new randomised trials. A prospective randomized phase III trial, LungART (Lung Adjuvant Radiotherapy Trial), designed with the primary aim of investigating the benefits of conformal radiotherapy in completely resected pN2 NSCLC, together with adjuvant chemotherapy, is currently ongoing in Europe, and should help answering definitely this question, investigators are strongly encouraged to enroll patients on this randomized trial. 1 : PORT Meta-analysis Trialists Group. Postoperative radiotherapy in non-small-cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised controlled trials. PORT Meta-analysis Trialists Group. Lancet 1998; 352:257-63. 2 : PORT Meta-analysis Trialists Group: Postoperative radiotherapy for non-small cell lung cancer. Cochrane Database Syst Rev 2:CD002142, 2005 3 : Kepka L, Bujko K, Orlowski TM, et al. Cardiopulmonary morbidity and quality of life in non-small cell lung cancer patients treated with or without postoperative radiotherapy. Radiother Oncol 2011;98:238–43. 4 : Lally BE, Zelterman D, Colasanto JM, et al. Postoperative radiotherapy for stage II or III non-small-cell lung cancer using the surveillance, epidemiology, and end results database. J Clin Oncol 2006; 24:2998-3006. 5 : Douillard JY, Rosell R, De Lena M, et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer. Adjuvant Navelbine International Trialist Association ANITA: a randomised controlled trial. Lancet Oncol 2006;7: 719-27. 6 : Robinson CG, Patel AP, Bradley JD et al. Postoperative radiotherapy for pathologic N2 Non small Cell lung cancer treated with adjuvant chemotherapy : A review of the National Cancer Data Base. J Clin Oncol 2015 ; 33 :870-77
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MINI 25 - Trials, Radiation and Other (ID 142)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:J.M. Clavero, R. Hassan
- Coordinates: 9/08/2015, 16:45 - 18:15, 702+704+706
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MINI25.10 - Discussant for MINI25.06, MINI25.07, MINI25.08, MINI25.09 (ID 3431)
16:45 - 18:15 | Author(s): F. Mornex
- Abstract
- Presentation
Abstract not provided
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MINI 33 - Radiotherapy and Complications (ID 164)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Locoregional Disease – NSCLC
- Presentations: 1
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MINI33.06 - Prospective Monitoring of Lung Function Test with CO and NO Diffusion during Thoracic Radiotherapy: Preliminary Results of the CONORT Study (ID 2402)
18:30 - 20:00 | Author(s): F. Mornex
- Abstract
- Presentation
Background:
Thoracic radiotherapy is a usual treatment for lung cancer; either at early-stages (stereotactic mode) or at locally advanced stages (conventional radiotherapy mode). Thoracic irradiation appears to have little impact on lung volume such as forced expiratory volume in one second (FEV1) or forced vital capacity (FCV). By contrast, carbon monoxide diffusing capacity (TLCO) may be altered under thoracic radiotherapy. Pulmonary diffusion may be also evaluated by the NO (azote monoxide) diffusion capacity (TLNO). Moreover, double assessment of NO and CO diffusing capacities open the way to understand if alteration of lung diffusion is due to alveolar membrane and/or a pulmonary capillary alteration. CONORT aims at measuring pulmonary function tests (PFTs), in particular the CO and NO diffusing capacity, during thoracic radiotherapy.
Methods:
Prospective multicenter study. CONORT study was approved by the Lyon Sud-Est IV ethics committee and the database was declared to the national information registry authority as required by French laws. Overall 112 patients must be included to estimate a difference of 15% in diffusing capacity test, with a 90% power and a 5% alpha risk. All consecutive patients treated by thoracic radiotherapy in Lyon Sud Hospital were included regardless of histology and radiotherapy technique. PFTs including double diffusion are performed by the same operator and using the same technic, before-, during-, at the end-, six weeks after- and six months after- thoracic irradiation. All included patients gave their consent. Results at PFTs were expressed in % of theoretical value (%th), and were compared using Student t test.
Results:
Between 1[st] February 2014 and 14 April 2015, 88 patients were included and 62 have been analyzed. Patients were male in 73%, mean age was 67.4 years. Radiotherapy technique was intensity-modulated radiation therapy (IMRT) in 61%, stereotactic radiotherapy (SBRT) in 32%, and 3D conformal radiotherapy in 7%. Mean pretreatment FEV1 was 2.06L (78.9% of the standard), mean FCV was 3.17L (94.9%), mean TLCO was 16.5 (64.7%) and mean TLNO was 72.7 (60.3%). FEV1 and FCV were stable during and after radiotherapy. However, mean TLCO decreased by 4.4% (P=0.01) between first and fourth PFT, mean DLNO decreased by 4% (P=0.001) between first and second PFT, mean VC (capillary lung volume) decreased by 6.24% between first and fourth PFT (P=0.011), and DM (membrane diffusing capacity) decreased by 3.6% between first and second PFT (P=0.001).
Conclusion:
CONORT is the first study evaluating the potential impact of thoracic radiotherapy on double measurement of lung diffusing capacity. These preliminary results showed that thoracic radiotherapy has little impact on lung volumes. However, lung diffusion decreases, initially by membrane alteration and then by capillary alteration. Results at 6 months showed that this alteration is fully recovered. Updated data will be presented at meeting.
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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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ORAL19.04 - Discussant for ORAL19.01, ORAL19.02, ORAL19.03 (ID 3337)
10:45 - 12:15 | Author(s): F. Mornex
- Abstract
- Presentation
Abstract not provided
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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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ORAL20.02 - Safety Results of the Consolidation Phase of a Phase III (PROCLAIM): Pemetrexed, Cisplatin or Etoposide, Cisplatin plus Thoracic Radiation Therapy followed by Consolidation Cytotoxic Chemotherapy in Locally Advanced Nonsquamous Non-Small Cell Lung Cancer (ID 645)
10:45 - 12:15 | Author(s): F. Mornex
- Abstract
- Presentation
Background:
Standard treatment for inoperable stage III non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy. However, many patients die from recurrent disease, indicating that new treatment strategies are needed.
Methods:
PROCLAIM is a phase III trial comparing overall survival in patients with unresectable stage III nonsquamous NSCLC receiving pemetrexed+cisplatin (PemCis) and concurrent radiotherapy for 3 cycles followed by 4 cycles of pemetrexed consolidation (Arm A) versus etoposide+cisplatin (EtoCis) and concurrent radiotherapy for 2 cycles followed by consolidation with a platinum-based doublet of choice for up to 2 cycles (Arm B). Possible consolidation therapies in Arm B were EtoCis, vinorelbine+cisplatin (VinCis), and paclitaxel+carboplatin (PacCarb). Overall efficacy and safety results for the intent-to-treat population will be presented in a separate disclosure. Safety was a secondary objective. Interim safety results for the concurrent phase were previously presented. Here we present safety results for the consolidation phase. Treatment-emergent adverse events (TEAEs) were assessed according to the Common Terminology Criteria for Adverse Events (v3.0, CTCAE). TEAE incidences were compared using Fisher’s exact test (two-sided α=0.05).
Results:
Of 598 randomized patients, 555 were treated in the concurrent phase (Arm A: N=283; Arm B: N=272), most of whom (Arm A: n=229 [80.9%]; Arm B: n=202 [74.3%]) continued on to the consolidation phase (Arm B patients: EtoCis [33.5%], PacCarb [26.8%], VinCis [14.0%]). Baseline characteristics, including age, gender, performance status, smoking status, stage, and origin, were well-balanced across arms. Percentages of patients in Arm A completing ≥2, ≥3, and 4 consolidation cycles were 95.2%, 84.3%, and 73.4%, respectively. Percentages of patients in Arm B completing 2 consolidation cycles (maximum) were EtoCis (89.0%), PacCarb (93.2%), and VinCis (86.8%). Mean dose intensities for pemetrexed, etoposide, vinorelbine, cisplatin, paclitaxel, and carboplatin were 95.4%, 94.0%, 84.2%, 91.2%, 88.7%, and 92.7%, respectively. More patients in Arm B, compared to Arm A, experienced dose reductions, dose omissions, and cycle delays. Patients in Arm B reported more grade 3/4/5 drug-related TEAEs than Arm A (51.0% versus 31.0%, p<0.001; Table). Rates of drug-related serious AEs were similar between groups (Arm A: 14.4%; Arm B: 13.4%).Drug-related Grade 3/4/5 TEAEs Occurring in ≥2% of Patients (or of Clinical Relevance) in the Consolidation Phase
CTCAE Arm A (N=229) n (%) Arm B (N=202) n (%) Neutrophils 27 (11.8) 76 (37.6)* Leukocytes 19 (8.3) 29 (14.4) Hemoglobin 6 (2.6) 9 (4.5) Platelets 5 (2.2) 10 (5.0) Febrile neutropenia 7 (3.1) 7 (3.5) Lymphopenia 8 (3.5) 5 (2.5) Pneumonitis/pulmonary infiltrates 5 (2.2) 2 (1.0) Fatigue 2 (0.9) 4 (2.0) Pneumonia 5 (2.2) 0 Esophagitis 0 3 (1.5) *p<0.001, Fisher’s exact test. Note: Of the TEAEs listed here, only one case (0.4%, Arm A, pneumonia) was grade 5.
Conclusion:
During the PROCLAIM consolidation phase, most patients were able to complete the planned number of cycles in either arm, with the highest dose intensity corresponding to pemetrexed. Pemetrexed consolidation had a significantly lower incidence of drug-related grade 3/4/5 TEAEs than the platinum doublets in Arm B. A more detailed analysis of Arm B (by treatment regimen) is underway.
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