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Dirk De Ruysscher
Moderator of
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OA12 - Profiling the Multidisciplinary Management of Stage III NSCLC (ID 144)
- Event: WCLC 2019
- Type: Oral Session
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 9
- Now Available
- Moderators:Dirk De Ruysscher, Bartomeu Massuti
- Coordinates: 9/09/2019, 15:45 - 17:15, Seoul (2007)
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OA12.01 - PCI for Radically Treated Non-Small Cell Lung Cancer: A Meta-Analysis Using Updated Individual Patient Data of Randomized Trials (Now Available) (ID 2624)
15:45 - 17:15 | Presenting Author(s): Willem Witlox | Author(s): Dirk De Ruysscher, Benjamin Lacas, Cecile Le Pechoux, Jean-Pierre Pignon, Matthias Guckenberger, Alexander Sun, Mary Redman, Si-Yu Wang, Chen Hu, Vincent Van Der Noort, Ning Li, Harm Van Tinteren, Harry JM Groen, Manuela Joore, Bram Ramaekers
- Abstract
- Presentation
Background
In localized non-small cell lung cancer (NSCLC), prophylactic cranial irradiation (PCI) reduced the incidence of brain metastases (BM) (relative risk 0.35), but without a demonstrated effect on overall survival (OS). This may be due to the small sample size in these individual randomized clinical trials (RCTs).
Therefore, we aimed to assess the impact of PCI on long term OS for radically treated stage III NSCLC patients compared to observation using updated individual patient data (IPD) from RCTs.
Method
The main endpoint was OS and secondary endpoints were progression-free survival (PFS), BM-free survival (BMFS) and toxicity. All analyses were performed based on the intention-to-treat principle. The median follow-up was estimated using the inverse Kaplan-Meier method. The log-rank observed minus expected number of events and its variance were used to calculate individual and overall pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) with a fixed effects model. Heterogeneity was studied using the Cochrane test and I2. Survival curves and 5-year difference between arms were estimated using the Peto method. Interaction between prognostic factors (age, performance status, and histology) and treatment allocation were assessed using Cox proportional hazards models. Toxicities grade ≥ 3 were reported descriptively.
Result
Data on four of the seven eligible trials (SWOG 8300, RTOG 0214, Guangzhou 2005 and NVALT-11) were available for this IPD meta-analysis. In total, 924 patients were analyzed of which 68% was male, median age was 61 years, 94% of the patients had a performance status ≤ 1 and 37% had squamous histology. The median follow-up was 8.1 years. All trials provided sufficient IPD for the three endpoints, except for the SWOG 8300 trial (OS only). This trial explained inter-trial heterogeneity. Because of the qualitative interaction with the other trials (p=0.0062) it was separately analyzed (N=254). Compared to observation, OS was significantly lower for PCI in the SWOG 8300 trial (HR 1.38, 95% CI [1.07 to 1.79] p=0.013, 5-year absolute difference -0.9%, 95% CI [-5.9 to 4.1]). However, for the other trials (N=670) no significant OS difference was observed (HR 0.90, 95% CI [0.76 to 1.07] p=0.228, 5-year absolute difference 1.8%, 95% CI [-5.2 to 8.8]). PFS (HR 0.78, 95% CI [0.65 to 0.92] p=0.004, 5-year absolute difference 4.8%, 95% CI [-1.2 to 10.8]) and BMFS (0.38, 95% CI [0.27 to 0.53] p<0.001, 5-year absolute difference 20.7%, 95% CI [12.2 to 29.2]) were significantly higher in the PCI arm. There was no interaction between prognostic factors and treatment allocation for OS. Toxicity data for the PCI arm was available in all trials except the SWOG 8300 trial. The total number of patients with at least one grade ≥3 toxicity (for the adverse events pre-specified in the protocol) in the PCI arm was 19/456, including 11/86 in the NVALT-11 trial. Toxicity for the observation arm was only available in the NVALT-11 trial, including 4/88 patients with at least one grade ≥3 toxicity.
Conclusion
Although PFS and BM-free survival were improved for patients who received PCI, no significant PCI benefit for OS was observed.
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OA12.02 - Randomized Phase II Study of CDDP+S-1 vs CDDP+PEM Combined with Thoracic RT for Locally Advanced Non-Sq NSCLC: SPECTRA Study (Now Available) (ID 428)
15:45 - 17:15 | Presenting Author(s): Takashi Seto | Author(s): Seiji Niho, Tatsuya Yoshida, Tetsuo Akimoto, Kentaro Sakamaki, Akira Ono, Makoto Nishio, Noboru Yamamoto, Toyoaki Hida, Hiroaki Okamoto, Takayasu Kurata, Yoshihiro Hattori, Koichi Goto, Takeharu Yamanaka, Yuichiro Ohe
- Abstract
- Presentation
Background
SPECTRA, a multicenter, randomized phase II study of CDDP+S-1 versus CDDP+pemetrexed (PEM) combined with thoracic radiotherapy (TRT) for locally advanced non-squamous non-small cell lung cancer (NSCLC), previously reported that toxicities were tolerable and manageable in both arms; however, febrile neutropenia was more frequently observed in the CDDP+S-1 arm (9.6%/2%). Completion rate of TRT (60Gy) and chemotherapy (4 cycles) was 92%/98% and 73%/86%, respectively. Response rate was 60%/64% (WCLC 2017, MA17.06). Here, we present primary analysis of 2-year survival data.
Method
Patients were randomly assigned to receive CDDP+S-1 (CDDP 60mg/m2, d1, and S-1 80mg/m2, d1-14, q4w, up to 4 cycles) or CDDP+PEM (CDDP 75mg/m2, d1, and PEM 500mg/m2, d1, q3w, up to 4 cycles) combined with TRT 60Gy in 30 fractions. The primary endpoint was 2-year progression-free survival (PFS) rate. The sample size was set at 100 patients.
Result
Between Jan 2013 and Oct 2016, 102 patients were enrolled in this study from 9 institutions in Japan. All 102 patients were eligible and assessable, of whom 52 were assigned to CDDP+S-1 and 50 to CDDP+PEM. Baseline characteristics were similar (CDDP+S-1/CDDP+PEM): median age (range) 64.5 (39-73)/63.5 (32-74) years; women, n=17 (33%)/n=17 (34%); stage IIIB, n=21 (40%)/n=20 (40%); ECOG PS of 1, n=14 (27%)/n=14 (28%); never smoker, n=12 (23%)/n=12 (24%); and adenocarcinoma, n=47(90%)/n=45(90%); activating EGFR mutation, n=9 (17%)/n=4 (8%); ALK fusion, n=2 (4%)/n=3 (6%). A total of 72 PFS events were observed at the data cut-off (28 November 2018). After a median follow-up of 32.1 months, median PFS was 12.7/13.8 months (HR=1.16, 95% CI, 0.73-1.84, p=0.538), and 2-year PFS rate was 36.5% (95% CI, 23.5-49.6)/32.1% (95%CI, 18.9-45.4). Disease progression was observed in 33 and 36 patients. Distant metastases were the first site of failure in 24 and 31 patients. Local relapse as the first site of failure was observed in 14 and 13 patients. After a median follow-up of 34.6 months, 44 OS events were observed. Median OS was 48.3/59.1 months (HR=1.05, 95%CI, 0.58-1.90, p=0.883), and 2-year OS rate was 69.2% (95%CI, 56.7-81.8)/66.4% (95%CI, 53.0-79.9). 27 patients in each arm received post-study chemotherapy including EGFR-TKIs (n=7/n=5), ALK-TKIs (n=0/n=3), and immune checkpoint inhibitors (n=6/n=10).
Conclusion
2-year PFS rate in the CDDP+S-1 arm was better than that in the CDDP+PEM arm. We will select the CDDP+S-1 arm as the investigational arm in a future phase III study. UMIN000009914 (release date: 31/Jan/2013)
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OA12.03 - Initial Reporting of NRG-LU001, Randomized Phase II Trial of Concurrent Chemoradiotherapy +/- Metformin HCL in Locally Advanced NSCLC (Now Available) (ID 1868)
15:45 - 17:15 | Presenting Author(s): Heath Skinner | Author(s): Chen Hu, Theodoros Tsakiridis, Rafael Santana-Davila, Bo Lu, Jeremy Erasmus, Anthony Doemer, Gregory Videtic, James Coster, Alex Xuexhong Yang, Richard Lee, Maria Werner Wasik, Phillip Schaner, Steven McCormack, Benjamin Esparaz, Rondal McGarry, Jose Bazan, Timothy Stuve, Jeffrey D Bradley
- Abstract
- Presentation
Background
Preclinical and retrospective clinical data, have shown that metformin, an inexpensive diabetes drug, has the potential to improve response to chemotherapy and radiation in several solid tumors, including non-small cell lung cancer (NSCLC). These findings led to NRG-LU001, a multi-institutional, international randomized Phase II clinical trial to determine whether metformin can improve outcomes of curative chemoradiation (CRT) in locally advanced NSCLC (LA-NSCLC).
Method
Unresectable stage IIIA/B NSCLC patients were randomized to either concurrent chemoradiation to 60 Gy with weekly carboplatin-paclitaxel (CP), followed by consolidation CP (Control) or the same regimen combined with metformin (2000 mg/day) (Experimental). The primary endpoint was 1-year progression free survival (PFS). PFS and overall survival (OS) were estimated using the method of Kaplan-Meier. Time to loco-regional progression (TTLRP) or distant metastasis (TTDM) were estimated using the cumulative incidence method. Adverse events (AEs) were graded using CTCAE v4.0.
Result
170 patients were randomized between Aug. 2014-Dec. 2016, with planned analysis at 102 events. No significant difference in toxicity was observed between Control and Experimental arms. 1- and 2-year PFS was 60.4% (95% CI: 48.5, 70.4) and 40.1% (95% CI: 29.0, 51.0) in Control vs 51.3% (95% CI: 39.8, 61.7) and 34.5% (95% CI: 24.2, 45.1) in the Experimental arm (multivariable Cox proportional HR=1.20 (95% CI: 0.81, 1.78), p=0.36). On multivariable analysis including treatment arm, performance status, histology and stage, only higher stage (IIIA vs. IIIB) was associated with worse PFS (HR 1.79, 95% CI:1.19, 2.69, p=0.0054). OS at 2 years was 65.4% (95% CI: 53.5, 75.0) for Control vs 64.9% (95% CI: 53.1, 74.5) for the Metformin arm (HR=1.03 (95% CI: 0.64, 1.68)), while deaths due to disease were 90% vs 71%, respectively. No significant differences were found for TTLRP (HR 1.01, 95% CI: 0.57, 1.79, p=0.98) or TTDM (1.38, 95% CI: 0.76, 2.5, p=0.29). 63.4% of patients in the experimental arm received the complete course of metformin, with the most common cause of discontinuation being side effects or complications (13.4%).
Conclusion
In NRG-LU001, concurrent CRT and metformin presented no noticeable safety concerns. However, this combination failed to improve PFS at the hypothesized effect size. Additionally, no effect on OS or patterns of failure were identified. Blinded central review of imaging based PFS is ongoing. Somewhat unexpectedly, 37% of patients did not complete the prescribed course of metformin. Additionally, deaths due to disease were less in the experimental arm compared to control.
Acknowledgements: This project was supported by National Cancer Institute (NCI) grants: U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG SDMC), UG1CA189867 (NCORP), U24CA180803 (IROC). HS and TT are Co-Principal Investigators in this trial.
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OA12.04 - Discussant - OA12.01, OA12.02, OA12.03 (Now Available) (ID 3789)
15:45 - 17:15 | Presenting Author(s): Everett E. Vokes
- Abstract
- Presentation
Abstract not provided
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OA12.05 - Imaging-Guided Target Volume Reduction in Radiotherapy of Lung Cancer: The Prospective Randomized Multinational PET-Plan Trial (Now Available) (ID 2558)
15:45 - 17:15 | Presenting Author(s): Eleni Gkika | Author(s): Ursula Nestle, Tanja Schimek-Jasch, Stephanie Kremp, Andrea Schaefer, Andreas Kuesters, Marco Tosch, Thomas Hehr, Martina Eschmann, Yves-Pierre Bultel, Peter Hass, Jochen Fleckenstein, Alexander Thieme, Marcus Stockinger, Matthias Miederer, Gabriele Holl, Christian Rischke, Sonja Adebahr, Jochem Koenig, Anca-Ligia Grosu
- Abstract
- Presentation
Background
Advanced medical imaging offers a chance for target volume reduction in modern radiotherapy, which may lead to more effective local treatments with reduced toxicity and offer the protection of draining lymph nodes and large vessels, possibly of importance for the upcoming combination of radiotherapy and immunotherapy. Locally advanced non-small cell lung cancer (NSCLC) with improvable local control and high toxicity is an excellent model to investigate this topic.
Method
In the prospective randomised controlled PET-Plan trial (NCT00697333), patients with inoperable stage II/III NSCLC and an indication for radiochemotherapy were randomized at a 1:1 ratio. In conventional arm A target volumes were informed by FDG-PET and CT plus elective nodal irradiation and in experimental arm B they were solely informed by FDG-PET. In both arms, quality assured isotoxically dose-escalated IMRT or 3D-CRT (60 - 74Gy, 2Gy per fraction) was planned and applied to the respective target volumes along with simultaneous platinum-based chemotherapy. The primary objective was time to locoregional progression (LRP) in terms of non-inferiority of experimental arm B.
Result
311 patients were recruited, 205 patients included in the intent to treat (ITT) (A: n=99, B: n=106) and 172 patients in the per protocol (PP) analysis (A: n=84, B: n=88). Median FU time in the PP set was 16 months. Non-inferiority of experimental arm B was confirmed for the pre-specified non-inferiority margin. The risk of LRP was lower in the experimental arm B (2y-LRP 0.20 vs. 0.39; HR=0·57; 95% CI: 0·30–1·06; p=0·039) with no difference between study arms concerning survival (2y-OS 0.57 vs. 0.54), out-field recurrence and toxicity.
Conclusion
In radiochemotherapy for locally advanced NSCLC PET-Imaging based reduction of radiotherapy target volumes is feasible and may improve local control without increasing toxicity. However, in this trial there was no impact on survival. The procedures established in this clinical trial provide a radiotherapy standard for future NSCLC-trials including immunotherapy and may furthermore inspire trials on imaging based target volume reduction for other types of tumours.
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OA12.06 - A Prospective Randomized Phase Ⅲ Study of Precise PORT for Patients with pⅢA-N2 NSCLC After Complete Resection and Adjuvant Chemotherapy (Now Available) (ID 2487)
15:45 - 17:15 | Presenting Author(s): Zhouguang Hui | Author(s): Yu Men, Chen Hu, zongmei Zhou, Jun Liang, qinfu Feng, Bi Nan, Xin Wang, Dongfu Chen, zefen Xiao, Jima Lv, Lei Deng, Tao Zhang, wenqing Wang, Shugeng Gao, Jie He, Luhua Wang
- Abstract
- Presentation
Background
For patients with completely resected pⅢA-N2 non-small cell lung cancer (NSCLC), the role of postoperative radiotherapy (PORT) is not well defined. 3D-conformal or simplified intensity modulated radiotherapy (3D-CRT/sIMRT) can precisely deliver high dose to the target volume while decreasing the toxicity of normal tissues, which may improve the treatment outcomes. This phase III randomized clinical trial (NCT00880971) is designed to evaluate the effect of precise PORT on survival and failure pattern in patients with pⅢA-N2 NSCLC after complete resection and adjuvant chemotherapy.
Method
After complete resection and four cycles of platinum based chemotherapy, patients with pⅢA-N2 NSCLC were randomized equally into PORT group or observation group. Using 3D-CRT/sIMRT techniques, PORT of 50 Gy by 25 fractions was given to the ipsilateral hilum, subcarinal region and ipsilateral mediastinum. The primary endpoint was disease free survival (DFS). Secondary endpoints include overall survival (OS), loco-regional recurrence free survival (LRFS), distant metastasis free survival (DMFS) and toxicity. Targeted accrue was 360 patients. With at least 230 DFS events it was designed to detect an improvement in 3-year DFS from 30% to 44% (equivalent to HR=0.69) at 1-sided type 1 error of 0.025 with 80% power. Intent-to-treat populations is used for primary analyses, supplemented with sensitivity analyses using per-protocol population. Log-rank test is used for time-to-event data comparisons.
Result
Between Jan. 2009 and Dec. 2017, 364 consecutive eligible patients were randomized, including 184 in the PORT group and 180 in the observation group. For this initial reporting of planned final analysis, as Jan 31, 2019, 230 DFS events were reported and the median follow up time was 53.3 months. The clinical features were comparable between the two groups. The 3-year DFS rates in PORT and observation were 42.7% vs. 34.5% (mDFS: 26.5 vs 22.7 months, HR=0.85, 95% CI: 0.65-1.10, 1-sided p=0.10), with OS of 81.5% vs. 85.4% (mOS: not reached vs 90.9 months, HR=1.01, 95% CI: 0.68-1.51, 2-sided p=0.94), LRFS of 69.8% vs. 62.4% (HR=0.71, 95% CI: 0.51-0.97, 2-sided p=0.03), and DMFS of 44.8% vs. 43.5% (HR=0.93, 95% CI 0.71-1.22, 2-sided p=0.60), respectively. For 310 per-protocol patients (140 with PORT and 170 without PORT), PORT marginally improve the DFS (44.8% vs 32.6%, HR=0.76, 95% CI: 0.57-1.00, 2-sided p=0.05), but not OS (85.7% vs 85.0%, HR=0.83, 95% CI: 0.53-1.30, p=0.41). Relapses of any type were observed in 110 (59.8%) and 116 patients (64.4%) in the PORT and observation groups, respectively. Forty-seven over 50 deaths (94.0%) in the PORT group and 42 over 47 deaths (89.4%) in the observation group died of cancer progression, respectively. No radiotherapy-related grade 5 AE was observed.
Conclusion
For pⅢA-N2 NSCLC patients after complete resection and adjuvant chemotherapy, precise PORT has not been shown to significantly improve DFS or OS , though it can significantly improve LRFS.
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OA12.07 - Radicality of Lymphadenectomy in Lung Cancer According to Surgical Approach. Results from the Spanish Group of Video-Assisted Thoracic Surgery (Now Available) (ID 1062)
15:45 - 17:15 | Presenting Author(s): Carme Obiols | Author(s): Sergi Call, Ramon Rami-Porta, Angeles Jaen, David Gomez De Antonio, Silvana Crowley, Iñigo Royo, Raúl Embún
- Abstract
- Presentation
Background
The minor standard of systematic nodal dissection (SND) in lung cancer surgery, which is the minimum recommended by the Union for International Cancer Control, requires the resection/sampling of, at least, 3 mediastinal (including subcarinal station) and 3 hilar/intrapulmonary lymph nodes (LN). The objective of this study is to analyze differences in intraoperative LN assessment in patients with surgically treated non-small cell lung cancer (NSCLC) according to surgical approach (open vs VATS), from the results of the Spanish Group of Video-Assisted Thoracic Surgery (GEVATS) database.
Method
Prospective multicenter cohort study of anatomic pulmonary resections (n=3533) performed from 20/12/16 to 20/03/18. Exclusions criteria were: indications different from NSCLC, previous lung cancer, synchronous tumors and induction therapy. Patients who did not meet the criteria for SND but had no nodal involvement were coded as pathologic (p)Nx (instead of pN0). Corresponding tests for homogeneity were performed. Multiple logistic regression analysis was used to determine the odds ratio (OR) and 95% confidence interval (95%CI). Stata/SE vs 13 statistical package was used for data analysis. Significance was considered when p<0.05.
Result
2532 patients were analyzed (1801 men [71.1%]; median age: 67 years). SND was performed in 65%, with a median of LN resected/sampled of 7 (IQR 4-12) and a rate of pN2 of 9.5%. Table1 summarizes results from bivariate analysis.Independent risk factors for thoracotomy at multivariate analysis (OR; 95%CI) were: squamous cell carcinoma vs adenocarcinoma (1.3; 1.04-1.68), staging mediastinoscopy (2.8; 1.83-4.22), LN resected (1.02; 1.00-1.04), SND (1.4; 1.07-1.8), tumour >3cm (1.8; 1.5-2.2), central tumour (2.5; 2.0-3.1); pN1 (1.5; 1.1-2.1) and pN2 (1.6; 1.1-2.3). A significantly higher proportion of nodal upstaging was observed in thoracotomy group: from cN0 to pN1/pN2, and from cN1 to pN2 (table1).
Conclusion
The intensity of lymphadenectomy in GEVATS was superior in the thoracotomy approach. Therefore, intraoperative lymph node evaluation performed at VATS should improve to have better prognostic information and indicate adjuvant therapy.
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OA12.08 - Discussant - OA12.05, OA12.06, OA12.07 (Now Available) (ID 3790)
15:45 - 17:15 | Presenting Author(s): José Belderbos
- Abstract
- Presentation
Abstract not provided
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OA12.09 - James D. Cox Lectureship Award for Radiation Oncology (Now Available) (ID 3902)
15:45 - 17:15 | Presenting Author(s): Corinne Faivre-Finn
- Abstract
- Presentation
Abstract not provided
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Author of
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ES23 - Optimal Management of N2 Disease in the Era Of IO (ID 26)
- Event: WCLC 2019
- Type: Educational Session
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Now Available
- Moderators:Alex Martinez-Marti, Hong-Xu Liu
- Coordinates: 9/10/2019, 11:30 - 13:00, Hilton Head (1978)
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ES23.04 - Optimal Supportive Care During and After Concurrent Chemoradiotherapy and I/O (Now Available) (ID 3284)
11:30 - 13:00 | Presenting Author(s): Dirk De Ruysscher
- Abstract
- Presentation
Abstract
Concurrent chemotherapy and radiotherapy (CCRT) is the treatment of choice for most fit patients with locally advanced NSCLC. Recently, adjuvant durvalumab has improved the overall survival further.
However, CCRT is a toxic treatment. Treatment-related deaths occur in a few percent of patients and many suffer severe side effects that require medical interventions and even in-patient care.
In contrast to extensive research on infections and emesis, most data on other important side effects are scant.
Two examples of this are acute esophagitis and cough and dyspnea.
Correlation between dysphagia and endoscopic findings
In a prospective trial with 38 patients receiving radiotherapy alone for lung cancer, an endoscopy was done during radiotherapy when patients had received a dose of 30-40 Gy on the esophagus. Eighteen patients (47 %) had dysphagia of any grade, but only in 12 of them (67 %) endoscopy showed esophagitis. Of the remaining 20 patients without complaints, 5 (25 %) had endoscopic signs of esophagitis. Gastritis was found in 18 patients (47 %), with or without esophagitis.
In another study, 82 NSCLC patients were evaluated by endoscopy. There was a good correlation between the RTOG clinical score for dysphagia and the endoscopic findings (Spearman rank correlation coefficient 0.428; p< 0.0001). All patients with clinical grade 3 dysphagia had endoscopic grade 2 or 3 esophagitis. Also in case of RTOG grade 2 dysphagia, all patients had endoscopic esophagitis, although 40 % had endoscopic grade 1 and 27 % had endoscopic grade 3 esophagitis. Of patients with or without only mild (grade 1) dysphagia, 11 % showed grade 3 endoscopic esophagitis. Sixteen percent of patients has esophageal candidiasis, but its relation with dysphagia or endoscopic grade of esophagitis was not reported. No data on the incidence of gastritis were given.
Effect of radiotherapy on esophageal motility
An impaired esophageal motility may also lead to dysphagia.
The esophageal transit time (ETT) before and during (10 Gy and 30 Gy) radiotherapy alone was evaluated in 11 patients. An increase in the ETT was seen in 9 of 11 patients (82%) (p<0.05).
The ETT was also investigated in 18 breast cancer patients receiving radiotherapy to the inner quadrants of the breast using a dose of 50 Gy/ 25 fractions. The cranial part of the esophagus received a mean dose of 6 Gy/ 25 fractions, and the distal two-thirds a mean dose of 15.3 Gy/ 25 fractions. Comparing the ETT before and after radiotherapy, for the upper third and the distal two-thirds of the esophagus, the ETT increased from 4.77 ± 1.08 sec. to 6.92 ± 2.15 sec., from 11.22 ± 2.85 sec to 23.30 ± 5.65 sec. and from 11.61 ± 2.97 sec. to 23.74 ± 5.70 sec., respectively (p<0.001).
Because of the motility impairment even at very low radiotherapy doses, the use of proton pump inhibitors is logical.
Prevention and treatment of acute esophagitis
In a randomized study with advanced NSCLC patients, treated with radiotherapy alone or radiotherapy plus amifostine, amifostine reduced the incidence of esophagitis in week 4 during radiotherapy from 42 % (31/73) to 4 % (3/73) (p<0.001), without decreasing the tumor response 2 months after treatment. In a larger randomized series of the RTOG, 243 stage II-III NSCLC patients were enrolled and randomized between carboplatin-paclitaxel concurrent chemo-radiotherapy with or without amifostine. No significant differences between the arms regarding overall survival, disease-free survival or long-term toxicity were observed.
In another study, 60 stage III NSCLC patients were randomized between concurrent carboplatin-paclitaxel and radiotherapy with or without amifostine. No significant difference in esophagitis was observed.
Therefore, amifostine has no consistently proven effect of preventing acute radiation-induced esophagitis.
In a small double-blind study, 14 stage III NSCLC patients were randomized between placebo or prophylactic indomethacin. Endoscopically-assessed esophagitis seemed to be milder, but no firm conclusions could be drawn.
Another small, placebo-controlled randomized trial, investigated naproxen in 28 stage III NSCLC patients receiving radiotherapy alone. There were no differences in clinical or endoscopic esophagitis rates. Eight patients (29 %) developed esophageal candidiasis, with no difference between the groups.
A placebo-controlled randomized trial could not demonstrate a beneficial effect of sucralfate on dysphagia.
In NRG/ RTOG 1012, patients were randomized between prophylactic Manuka honey, either in liquid or in lozenge form, and standard supportive care during concurrent chemo-radiotherapy for NSCLC. Standard supportive care consisted of a compound containing viscous lidocaine, an antacid such as magnesium aluminum oxide, and liquid or solid oxycodone, 5–10 mg, every 3 hours as needed. The primary endpoint was patient-reported pain on swallowing utilizing an eleven point (0–10) scale at 4 weeks (Numerical Rating Pain Scale, NRPS). Fifty-three patients were randomized to supportive care, 54 randomized to liquid honey and 56 to lozenge honey. There was no significant difference in the primary endpoint of change in the NRPS at 4 weeks between arms. There were no differences in any of the secondary endpoints except for opioid use at 4 weeks during treatment between the supportive care and liquid honey arms (p=0.03), with 52 % vs. 67 % of patients experiencing no pain with liquid honey. No difference was observed with lozenge honey. with more patients on the supportive care arm taking opioids. However, the differences were only observed at 4 weeks and not at the end of radiotherapy.
From this example, already, it is clear that more in-depth knowledge of the physiopathology of radiation injury is needed. A joint task force between ESTRO and ESMO members will address a spectrum of supportive care interventions in patients receiving concurrent chemotherapy and radiotherapy for lung cancer.
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OA12 - Profiling the Multidisciplinary Management of Stage III NSCLC (ID 144)
- Event: WCLC 2019
- Type: Oral Session
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Now Available
- Moderators:Dirk De Ruysscher, Bartomeu Massuti
- Coordinates: 9/09/2019, 15:45 - 17:15, Seoul (2007)
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OA12.01 - PCI for Radically Treated Non-Small Cell Lung Cancer: A Meta-Analysis Using Updated Individual Patient Data of Randomized Trials (Now Available) (ID 2624)
15:45 - 17:15 | Author(s): Dirk De Ruysscher
- Abstract
- Presentation
Background
In localized non-small cell lung cancer (NSCLC), prophylactic cranial irradiation (PCI) reduced the incidence of brain metastases (BM) (relative risk 0.35), but without a demonstrated effect on overall survival (OS). This may be due to the small sample size in these individual randomized clinical trials (RCTs).
Therefore, we aimed to assess the impact of PCI on long term OS for radically treated stage III NSCLC patients compared to observation using updated individual patient data (IPD) from RCTs.
Method
The main endpoint was OS and secondary endpoints were progression-free survival (PFS), BM-free survival (BMFS) and toxicity. All analyses were performed based on the intention-to-treat principle. The median follow-up was estimated using the inverse Kaplan-Meier method. The log-rank observed minus expected number of events and its variance were used to calculate individual and overall pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) with a fixed effects model. Heterogeneity was studied using the Cochrane test and I2. Survival curves and 5-year difference between arms were estimated using the Peto method. Interaction between prognostic factors (age, performance status, and histology) and treatment allocation were assessed using Cox proportional hazards models. Toxicities grade ≥ 3 were reported descriptively.
Result
Data on four of the seven eligible trials (SWOG 8300, RTOG 0214, Guangzhou 2005 and NVALT-11) were available for this IPD meta-analysis. In total, 924 patients were analyzed of which 68% was male, median age was 61 years, 94% of the patients had a performance status ≤ 1 and 37% had squamous histology. The median follow-up was 8.1 years. All trials provided sufficient IPD for the three endpoints, except for the SWOG 8300 trial (OS only). This trial explained inter-trial heterogeneity. Because of the qualitative interaction with the other trials (p=0.0062) it was separately analyzed (N=254). Compared to observation, OS was significantly lower for PCI in the SWOG 8300 trial (HR 1.38, 95% CI [1.07 to 1.79] p=0.013, 5-year absolute difference -0.9%, 95% CI [-5.9 to 4.1]). However, for the other trials (N=670) no significant OS difference was observed (HR 0.90, 95% CI [0.76 to 1.07] p=0.228, 5-year absolute difference 1.8%, 95% CI [-5.2 to 8.8]). PFS (HR 0.78, 95% CI [0.65 to 0.92] p=0.004, 5-year absolute difference 4.8%, 95% CI [-1.2 to 10.8]) and BMFS (0.38, 95% CI [0.27 to 0.53] p<0.001, 5-year absolute difference 20.7%, 95% CI [12.2 to 29.2]) were significantly higher in the PCI arm. There was no interaction between prognostic factors and treatment allocation for OS. Toxicity data for the PCI arm was available in all trials except the SWOG 8300 trial. The total number of patients with at least one grade ≥3 toxicity (for the adverse events pre-specified in the protocol) in the PCI arm was 19/456, including 11/86 in the NVALT-11 trial. Toxicity for the observation arm was only available in the NVALT-11 trial, including 4/88 patients with at least one grade ≥3 toxicity.
Conclusion
Although PFS and BM-free survival were improved for patients who received PCI, no significant PCI benefit for OS was observed.
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