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Tomoki Kimura
Moderator of
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MA 09 - The Current Status of Radiation Oncology (ID 666)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Locally Advanced NSCLC
- Presentations: 12
- Moderators:Tomoki Kimura, Yong Chan Ahn
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 316
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- Abstract
- Presentation
Background:
Lobectomy is the preferred treatment for patients with early stage non-small cell lung cancer (NSCLC). However, stereotactic body radiation therapy (SBRT) is an attractive option due to its promising efficacy reported recently. Given that prospective comparative data on lobectomy and SBRT are limited, we compared the two treatments for early stage NSCLC.
Method:
All patients undergoing treatment with lobectomy or SBRT for clinical early stage (T size≤5cm) NSCLC between January 2012 and June 2017 were reviewed. Age, gender, tumor characteristics, Charson Comorbidity Index, pulmonary function, local control rate (LCR), recurrence-free survival (RFS), overall survival (OS) data were collected and propensity matching performed.
Result:
For the entire lobectomy cohort, 3-year OS, DFS, and LCR were 87.9%, 84.9%, and 96.4% respectively. For the entire SBRT cohort, 3-year OS, RFS and LCR were 84.4%, 60.7% and 93.4%, respectively. A total of 246 patients underwent surgery, and 117 received SBRT. There were statistically difference between surgical patient and SBRT patients in tumor histology(P<0.000). Surgical patients had tendency that have longer tumor size than SBRT patients (2.4±1.0 vs. 2.1±0.8, P=0.092). There were no statistically difference between lobectomy and SBRT group with age (68.9±6.6 vs.69.0±9.2, P=0.980), Eastern Coorperative Oncology Group performance scores, Charlson comorbidity Index, pulmonary function test result (FEV1 and predict FEV1), gender, T stage, and tumor location. A propensity matched comparison in a blinded manner (1:1 ratio, caliper distance=0.0025) based on age, gender, WHO performance status score, pulmonary function (forced expiratory volume in 1 second [FEV1] % and FEV1), and T stage resulted in 49 matched pairs. The follow-up period ranged from 0.3 to 60.0 months, with a median of 21.4 months. There were no differences between lobectomy and SBRT in LCR, respectively 97.1% and 100% (p=0.355) at 4 year. Also the 4-year RFS was comparable between groups, as 68.6% after lobectomy, versus 81.9% at 4 year after SBRT (p=0.963). The 4-year OS was similar in both groups, with 58.1% vs. 75.2% for lobectomy and SBRT (p=0.774). No patient experienced treatment-related death in both groups.
Conclusion:
This retrospective analysis found no significant difference in LCR, RFS and OS between lobectomy and SBRT. This study indicated matching these disparate cohorts of patients remains challenging. Participation in clinical trials is essential to define the indications and relative efficacy of lobectomy and SBRT in a high-risk population.
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MA 09.02 - Ultra-Central Tumours Treated with Stereotactic Body Radiotherapy: A Single Institutional Experience (ID 8758)
11:05 - 11:10 | Presenting Author(s): Meredith Elana Giuliani | Author(s): V.K.Y. Yau, S. Raman, S. Pineda, L. Le, A. Lau, Andrea Bezjak, John Cho, A. Sun, A.J. Hope
- Abstract
- Presentation
Background:
Stereotactic body radiotherapy of “ultra-central” (UC) lung tumours, PTV directly abuts/overlaps the proximal bronchial tree (PBT), trachea, esophagus, pulmonary vein/artery, are considered to be at higher risk of toxicity. The purpose of this study is to review the outcomes and toxicities of Ultra-central lung tumours, compared to central tumours.
Method:
A retrospective review based on a prospective database of patients treated with lung SBRT from January 2006- December 2015 was conducted. Patients with central tumours defined using RTOG 0813 criteria and ultracentral tumours were included. 115 patients (53%) received 60Gy/8 and 61 (28%) received 48Gy/4. At our institution, the recommended Dmax for esophagus is 45Gy and 40Gy for 8 and 4 fractions, respectively. The Dmax and D10cc constraints for trachea, proximal bronchial tree, heart, and major vessels (including pulmonary artery and vein) are 48Gy and 40Gy for 4 fractions and 64 and 60Gy for 8 fractions. Toxicity was graded using CTCAE v3.0. Log-rank test was used to compare overall and cause-specific survival. Local, regional, and distant recurrence were compared using Gray’s test.
Result:
215 tumours were analyzed (189 C and 26 UC). The median age for C and UC were 75 years and 72.5 years. Median tumour size and PTV volume were 2.2 cm (range 0.9-5.7) and 41.7 cm3 (range 9.7-246.3) (C group) and 2.5 cm (0.8-5.5) and 58.2 cm3 (16.8-238.3) (UC group). The percentage of squamous cell carcinoma was higher in the UC group (15%, n=29 in C; 38%, n=10 in UC). The median follow-up was 20.3 months (24.5 mo for patients still alive). Median overall survival (OS) and cause-specific survival (CSS) was 34 mo and 53.8 mo for C and 20.1 mo and 28.2 mo for UC, respectively. Differences in OS and CSS between the two groups did not meet statistical significance (p=0.24 and p=0.14, respectively). Local, regional, and distant failure rates were 3%, 8% and 18% in the central tumour group and 0%, 9% and 25% in the ultra-central tumour group at 2 years. There was no statistically significant difference found in the rates of recurrence between the two groups. The rates of any grade 2 or higher toxicity (hemoptysis, esophageal toxicity, cough, dyspnea, pneumonitis) was 9% (n=17) in the C and 7.7% (n=2) in UC group (p=0.89). There were no known grade 4 or 5 toxicities.
Conclusion:
In our experience, SBRT to ultra-central tumours resulted in effective local control and no excessive risk of toxicity compared to central tumours.
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MA 09.03 - Discussant - MA 09.01, MA 09.02 (ID 10841)
11:10 - 11:25 | Presenting Author(s): Takafumi Komiyama
- Abstract
- Presentation
Abstract not provided
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MA 09.04 - Increasingly Abnormal Pre-Treatment Diffusion Capacity Is Associated with Greater Local Failure After Lung SBRT (ID 7391)
11:25 - 11:30 | Presenting Author(s): Gregory M.M. Videtic | Author(s): C. Reddy, N. Woody, K. Stephans
- Abstract
- Presentation
Background:
We hypothesized that impaired pulmonary functions tests might predict for altered lung density which would interfere with the efficacy of radiotherapy. We therefore sought to determine if there are associations between pre-treatment [preTx] forced expiratory volume in 1 second (FEV1, in L and as % predicted [%p]) and diffusion capacity (DLCO, as %p) with local failure (LF) rates seen with lung stereotactic body radiotherapy (SBRT) for medically inoperable lung cancer.
Method:
From an IRB-approved institutional prospective SBRT registry of 1330 patients, we identified 557 treated definitively for medically inoperable early stage T1-T3N0M0 non-small cell lung cancer (NSCLC) between 2003 and 2016 for whom both preTx FEV1 and DLCO were available. Lung SBRT dose/fractionation for a given pt was at the discretion of the treating physician. LF was defined as progressive and increasing CT scan abnormalities confirmed by progressive and incremental increases in lesion SUVs on serial PET imaging, with or without biopsy. Predictors of LF were determined using competing risks regression and rates of local control were determined from cumulative incidence analysis.
Result:
Pt characteristics included: female gender (52.6%); median age 74 years (range 42-95); median KPS 80 (range 50-100); median preTx FEV1 and DLCO: 1.39L (range 0.26-3.87), 60 %p (range 13-151) and 52 %p (range 10-143), respectively. Tumor characteristics included: median diameter 2.2 cm (range 0.7-7.2); median PET SUVmax 7.7 (range 0.8-56); % as T stage 1a, 1b, 2a, 2b, 3: 40.2; 35.5; 18.9; 4.5; 0.9, respectively; “central” location (per RTOG 0813) 22.6%. Median follow up was 18.3 months. At analysis, 46.9% pts were alive. Treatment characteristics included 50 Gy/5 fractions (fx) for 235 pts (42.2%), 60 Gy/3 fx for 167 pts (30%), and other schedules for 155 pts (27.8%), with the latter excluded from analysis due to variability in schedules, leaving 402 pts (72.2%). Only dose was significantly associated with LF on multivariable analysis [p=0.0057; HR =3.416, 95% CI 1.429-8.166]. Three-year cumulative incidence of LF post-SBRT for 50 Gy/5fx and 60 Gy/3 fx was 15.2% and 2.3% [p=0.024], respectively. In subset analysis of the 50 Gy/5 fx, DLCO was significant for LF both as a continuous variable and as a categorical variable. The significant cut-off for DLCO was 45%p, such that 3-year LF at <45 was 24.7% (95% CI 13.6-35.8) and at > 45 was 10.6% (95% CI 5.3-16.0), [p=0.0234; HR =0.441, %95 CI 0.217-0.895[CR1] ]. There were no significant associations between LF and pulmonary functions tests for 60 Gy/3 fx.
Conclusion:
As preTx DLCO drops below 45 %p, our findings suggest local failure increases when lung SBRT is delivered as 50 Gy/5 fx for early stage NSCLC. This warrants validation in prospective series.
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MA 09.05 - Evidence in Favor of or against the Use of TKIs with Concurrent Cranial Radiotherapy in Patients with NSCLC and CNS Involvement (ID 8082)
11:30 - 11:35 | Presenting Author(s): Giannis Mountzios | Author(s): P. Economopoulou
- Abstract
- Presentation
Background:
Central nervous system (CNS) metastases, including brain metastases (BM) and leptomeningeal metastases (LM) represent a frequent complication of non-small cell lung cancer (NSCLC). Patients with CNS metastases comprise a heterogeneous group, with a median survival that ranges from 3 to 14 months. Local therapies, such as whole brain radiotherapy (WBRT), stereotactic radiosurgery (SRS) or surgical resection, are available treatment strategies for BM. Introduction of tyrosine kinase inhibitors (TKIs) in clinical practice has led to individualization of therapy based upon the presence of the exact abnormality, resulting in a major therapeutic improvement in patients with NSCLC who harbor epidermal growth factor receptor (EGFR) activating mutations or anaplastic lymphoma kinase (ALK) gene rearrangements, respectively, but their role in combination with radiotherapy is controversial
Method:
We performed a systematic literature review of published data in PUBMED, SCOPUS and COCHRANE databases, as well as a manual search of reported data in major congresses, using the terms "EGFR-TKIs", "ALK-TKIs", "CNS", "BM" or ""LM" and "concurrent radiotherapy" or "stereotactic radiotherapy" from January 2000 through May 2017. Only prospective or retrospective clinical trials and meta-analyses reported in English language were included
Result:Author/year Phase No of pts EGFR status Treatment groups Control Outcomes Lind et al 2009 I 11 NA Cohort 1: Erlotinib 100 mg +WBRT Cohort 2: Erlotinib 150 mg +WBRT -Grade 3-5 toxicity in cohort 2 -High IDCR Welsh et al 2013 II 40 EGFR mutant: 9 of 15 pts tested Erlotinib 150 mg + WBRT -ORR 86%, -Median OS 11.8 m -Median OS 19.1 m in EGFR mutant Sperduto et al 2013 III 126 (closed early) NA Arm 2:TMZ+WBRT+ SRS Arm 3: Erlotinib 150 mg + WBRT+SRS Arm 1: WBRT +SRS OS not improved with addition of drugs -No difference in CNS-TTP between the three arms -49% grade 3-5 toxicity in arm 3 Lee et al.2014 II 80 EGFR mutant 1 out of 35 pts tested WBRT + Erlotinib WBRT No difference in OS Ma et al. 2009 II 21 NA WBRT +Gefitinib ORR 86% -Median OS 13 m -No significant grade 3 toxicity Pesce et al 2012 Randomized Phase II 59 NA WBRT + Gefitinib vs WBRT+ TMZ Median OS 6.3 m (Gefitinib arm), 4.9 m (TMZ arm) -No relevant toxicity Zeng et al 2012 Retrospective 90 NA WBRT +Gefitinib Gefitinib Higher ORR and OS with WBRT+ Gefitinib Luo et al 2015 Metaanalysis 980 (8 trials) NA Radiotherapy + TKI (TKI group) Radiotherapy or Radiotherapy+ chemotherapy (non-TKI group) -Higher RR, CNS-TTP and OS in radiotherapy +TKI group -No difference is serious AEs jiang et al 2016I Metaanalysis 1552 (15 trials) NA Radiotherapy + TKI Radiotherapy or Radiotherapy+ chemotherapy Higher RR, DCR, CNS-TTP and OS in radiotherapy +TKI group -Increased rate of any grade AEs
Conclusion:
At this time, concurrent use of TKIs with radiotherapy, although appearing to be safe, is not recommended outside of a clinical trial. Interestingly, data in EGFR mutant patients treated with an EGFR-TKI alone prompt the question whether this could be a front line approach in patients with asymptomatic BM, reserving WBRT for symptomatic cases. In clinical practice, burden of extracranial disease might also guide treatment decisions; physicians might select not to discontinue a TKI during WBRT in case of extensive extracranial organ involvement Ongoing clinical trials are currently evaluating the effectiveness of concomitant use of radiotherapy and TKIs.
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MA 09.06 - Pulmonary Oligometastases Treated by Stereotactic Body Radiation Therapy (SBRT): A Nationwide Survey of 1,378 Patients (ID 8014)
11:35 - 11:40 | Presenting Author(s): Yuzuru Niibe | Author(s): T. Yamamoto, Hiroshi Onishi, H. Yamashita, K. Katsui, Y. Matsumoto, R. Oh, M. Aoki, Takashi Shintani, M. Myojin, K. Yamada, M. Kobayashi, M. Ozaki, Y. Manabe, K. Yahara, A. Nishikawa, H. Kakuhara, Y. Matsuoka, K. Yamamoto, T. Fukuda, Y. Ushijima, S. Ohashi, T. Kan, S. Kubota, T. Inoue, N. Yamaguchi, Y. Takada, K. Nagata, O. Suzuki, K. Shirai, A. Terahara, K. Jingu
- Abstract
- Presentation
Background:
The treatment outcomes of patients with pulmonary oligometastases treated by SBRT were evaluated; the oligometastases were classified into three groups (oligo-recurrence, sync-oligometastases, and unclassified oligometastases) and the outcomes compared.
Method:
This study was limited to patients who had a BED10 ≥75 Gy. Oligo-recurrence was defined as a primary lesion that was controlled, the number of metastases or recurrences in the lung was one to five, and the disease-free interval (DFI), the interval between initial therapy of the primary lesion and the date of recurrence in the lung, was ≥6 months. Sync-oligometastases were defined as: the primary lesion was active; the number of metastases or recurrences in the lung and the active primary lesion was one to five; and the DFI was zero. The definition of unclassified oligometastases was similar to that of oligo-recurrence, but the DFI was <6 months. All oligomtastases in this study were treated by local therapy for all active lesions including primary and metastatic lesions.
Result:
Between 2004 and 2015, 1378 patients (male/female = 893/485; PS 0/1/2/3 = 746/474/85/17) meeting the study definition of pulmonary oligometastases were treated by SBRT in 68 institutions in Japan. Their median age was 72 years (16-93 years). The primary region was lung in 421, colorectal in 348, head and neck in 113, and others in 618. Histopathology showed adenocarcinoma in 761, squamous cell carcinoma in 358, and others in 186. Oligostatus was oligo-recurrence in 1013, sync-oligometastases in 118, and unclassified oligometastases in 122. The median maximum tumor diameter (MTD) was 1.5 cm (0.3-6.5 cm). The number of target tumors was solitary in 1037 and multiple in 341. The median BED10 was 105.6 Gy (75-289.6 Gy). The median DFI was 17.9 months (0-424 months). The median follow-up time was 24.3 months (0.1-143.7 months). The 3-year overall survival (OS), relapse-free survival, and local control rates were 60.3% (95%CI: 57.1-63.3%), 32.6% (95%CI: 29.7-35.5%), and 81.4% (95%CI: 78.8-83.7%). Univariate analysis showed only oligostatus, sex, PS, DFI, MTD, primary region, and histopathology were significant. The 3-year OS was 64.0% (95%CI: 60.4-67.5%) for oligo-recurrence and 50.6% (95%CI: 42.9-57.8%; p<0.001) for the others. Multivariate analysis of OS showed that only oligostatus (others/oligo-recurrence: HR 1.43), MTD (>2 cm/<2 cm, HR 1.45), histopathology (others/adenocarcinoma: HR: 1.47), and sex (male/female: HR 1.38) were significant.
Conclusion:
Pulmonary oligometastases, oligo-recurrence, female sex, adenocarcinoma, and small-sized tumor could be factors associated with longer survival.
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MA 09.07 - Discussant - MA 09.04, MA 09.05, MA 09.06 (ID 10842)
11:40 - 11:55 | Presenting Author(s): Gerard G Hanna
- Abstract
- Presentation
Abstract not provided
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MA 09.08 - Receipt of Chest Radiation and Immune-Related Pneumonitis in Patients with NSCLC Treated with Anti-PD-1/PD-L1 (ID 10075)
11:55 - 12:00 | Presenting Author(s): Jarushka Naidoo | Author(s): K.R. Voong, S.Z. Hazell, C. Hu, J. Hayman, R. Hales, K.A. Marrone, C.L. Hann, David S Ettinger, J.L. Feliciano, V. Rowe, R.J. Kelly, Julie R Brahmer, Patrick M Forde
- Abstract
- Presentation
Background:
Immune-related pneumonitis (IR-pneumonitis) is a potentially fatal toxicity of anti-PD-1/PD-L1. This study investigates the role of chest radiotherapy (RT) and the development of IR-pneumonitis in NSCLC patients treated with anti-PD-1/PD-L1.
Method:
Between January 2011 and April 2017, NSCLC patients treated with anti-PD-1/PD-L1 either as part of a clinical trial or as standard-of-care at a tertiary academic cancer center, were identified. Patient demographics, treatment, adverse event and RT data including type of RT (SBRT, 2D/3D conformal RT, IMRT, multiple), timing of RT (pre or post PD-1/PD-L1), location of RT (chest/non-chest), and number of courses of chest-RT, were collected in an IRB-approved institutional database. IR-pneumonitis was diagnosed clinically by the treating investigator; patients with confirmed RT pneumonitis, progressive NSCLC, or active infection were excluded. Associations between patient, treatment and RT parameters, and development of any grade IR-pneumonitis were evaluated using Student’s t-test and Fisher’s exact tests.
Result:
Of 184 NCSLC patients identified: median age was 67 years (range: 39-88); 57% (n=105) were male, 75% (n=137) were former/current smokers, 64% (n=118) had adenocarcinoma histology, and 59% (n=109) had advanced NSCLC at diagnosis. Anti-PD-1/PD-L1 monotherapy was received in 74% (n=136, nivolumab: 107, pembrolizumab: 14, durvalumab: 7, other: 8) and combination therapy in 26% of patients (n=48, PD-1/CTLA-4: 13, PD-L1/CTLA-4: 5, PD-1/chemotherapy: 4, PD-1/other: 25, PD-L1/other; 1). Any RT was received by 129 patients (70%), and 96 patients received chest-RT (52%). Thirty-eight (21%) patients developed IR-pneumonitis of any grade. IR-pneumonitis incidence was numerically higher in patients receiving combination therapy compared with monotherapy (29%, n=14/48 vs. 18%, n=24/136, p=0.1). Former/current smokers had a higher incidence of pneumonitis compared with never smokers (25% vs. 12%, p=0.03). IR-pneumonitis incidence was numerically higher in patients receiving chest-RT compared with non-chest/no RT (25%, n=24/96 vs. 16%, n=14/88, p=0.15). Of 129 patients who received any RT, there was a trend towards increased IR-pneumonitis in patients who received chest RT compared with those who received non-chest RT (25%,n=24/96 vs 9%, n=3/33; p=0.08). Overall, there were no significant associations between chest-RT type, chest-RT timing, nor receipt of more than one chest-RT course, and development of IR-pneumonitis (p>0.05).
Conclusion:
IR-pneumonitis incidence is 21% and may be higher than reported in clinical trials. Smoking status is associated with the development of IR-pneumonitis. Receipt of chest-RT was numerically higher, but not statistically associated with, development of IR-pneumonitis after receipt of anti-PD-1/PD-L1 in patients with advanced NSCLC. Radiation parameters did not associate with the development of IR-pneumonitis.
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MA 09.09 - Isotoxic Dose-Escalated Radiotherapy (RT) in Non-Small Cell Lung Cancer (NSCLC) with Deep Inspiration Breath Hold (DIBH) (ID 10052)
12:00 - 12:05 | Presenting Author(s): Hannah Bainbridge | Author(s): A. Dunlop, D. McQuaid, R. Colgan, Sanjay Popat, N. Yousaf, J. Bhosle, Mary Obrien, M. Ahmed, I. Locke, F. McDonald
- Abstract
- Presentation
Background:
With interest in the use of isotoxic dose-escalated RT in treatment of inoperable NSCLC, this study investigated the impact of DIBH using the Active Breathing Coordinator™ (ABC- Elekta, Stockholm, Sweden) device on isotoxic dose escalation potential.
Method:
Following informed consent, a four-dimensional (4D) planning CT scan and a DIBH scan using the ABC device were acquired in patients sequentially in the same session. A motion-encompassing target volume on the 4D scan and a motion-managed target volume on the DIBH scan were created. The RayStation radiotherapy treatment planning system (research version 5.99.0.16) was used to generate two corresponding volumetric modulated arc therapy (VMAT) plans for each patient, following the guidelines of the isotoxic IMRT trial (NCT01836692). The target dose was escalated up to a maximum of 79.2 Gy in 44 twice daily fractions and plans optimised to minimise dose to normal tissues. Potential to escalate target dose and differences in dose-volume metrics between the plans were compared using the Wilcoxon signed-rank test.
Result:
21 patients were included. The mean total lung volume was significantly higher with DIBH compared to 4D scans with an increase of 44.7 % ± 17.4 % (mean ± standard deviation), p < 0.001). In 20/21 patients, the maximum target dose of 79.2 Gy was achievable in both plans, however in one patient 61.2 Gy was achieved with 4D compared to 75.6 Gy with DIBH planning. In the 20 patients achieving equivalent target dose-escalation, the mean lung dose was 17.0 Gy (± 0.3Gy ) with 4D versus 14.6 Gy (± 0.3 Gy) with DIBH (p < 0.001). There was a significant mean reduction in heart dose between the DIBH compared to 4D plans of 0.3 Gy (± 0.2 Gy, p< 0.001) and significant reductions in heart D100 %, D66 % and D33 %(p < 0.01). Mediastinal envelope and oesophageal doses were similar using both techniques.
Conclusion:
The use of DIBH compared to 4D planning aids lung and cardiac sparing in isotoxic dose escalated RT and for a small number of patients may allow an increase in target dose. Particularly given the interaction between lung and cardiac toxicity in locally advanced NSCLC treated with radical RT, use of DIBH for treatment may lead to a reduction in toxicity compared to a 4D approach. In acknowledgement of the use of a mid-ventilation technique in some institutions, comparison with this method is planned.
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MA 09.10 - Toward a Radiological Scoring System of Radiotherapy-Induced Lung Damage (ID 8336)
12:05 - 12:10 | Presenting Author(s): Catarina Veiga | Author(s): D. Landau, A. Devaraj, T. Doel, D. Hawkes, J.R. McClelland
- Abstract
- Presentation
Background:
There is no objective criteria to quantify radiotherapy-induced lung damage (RILD), leading to under-reporting of toxicity across centres and trials. Our objective is to build a radiological scoring system of RILD that correlates with decline in lung function.
Method:
Baseline and 12-month CT scans and formal respiratory function tests (FVC, FEV1 and DLCO) from 23 patients enrolled in an isotoxic chemoradiation clinical trial (IDEAL CRT) were available for central review. First, the presence of new CT findings of RILD was qualitatively scored into eleven sub-categories: consolidation, ground-glass opacities, traction bronchiectasis, reticulation, pleural thickening, pleural effusion, reduction in lung height, distortions of the diaphragm, fissures, anterior junction line and major airways. From these, three main categories were derived: parenchymal change, pleural changes and volume reduction. The correlation between number of features scored and decline in breathing function was investigated. Later, twelve imaging markers were defined to quantify the severity of the radiological findings. The correlation between each imaging marker and decline in breathing scores was also investigated.
Result:
Each patient scored either two or three (out of three) categories of damage. Differences in variation of FVC, FEV1 and DLCO between these two groups were statistically significant (p≤0.02). The number of sub-categories scored was moderately correlated with decline in FVC (ρ=-0.67, p<0.01), FEV1 (ρ=-0.41, p=0.05) and DLCO (ρ=-0.50, p=0.01). Six of the twelve imaging markers were moderately correlated with changes in FVC and FEV1 (ρ≈-0.5, p<0.05); five were weakly correlated (ρ≈-0.2, p<0.05). The strongest correlations were found for imaging markers that quantify change in lung volume and shape, mediastinal shift and pleural reaction. Figure 1 Figure- Relationship between radiological findings of RILD and changes in FVC.
Conclusion:
We investigated the relationship between radiological findings of RILD and decline in lung function. Our findings suggest that a scoring system can be proposed when investigated in a larger cohort.
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MA 09.11 - Isotoxic Intensity Modulated Radiotherapy (IMRT) in Stage III Non-Small Cell Lung Cancer (NSCLC) – a Feasibility Study (ID 7978)
12:10 - 12:15 | Presenting Author(s): Kate Haslett | Author(s): Neil Bayman, K.N. Franks, N. Groom, Gerard G Hanna, S.V. Harden, C. Harris, S. Harrow, M. Hatton, P. McCloskey, F. McDonald, L. Ashcroft, D.J. Ryder, Corinne Faivre-Finn
- Abstract
- Presentation
Background:
The majority of stage III patients with non-small cell lung cancer (NSCLC) are unsuitable for concurrent chemoradiotherapy. Alternative treatment options include sequential chemoradiotherapy and radiotherapy (RT) alone. As the rate of local failure is high there is a rationale for treatment intensification.
Method:
Isotoxic Intensity Modulated Radiotherapy (IMRT) is a multicentre feasibility study combining a number of intensification strategies; dose escalation, acceleration and hyperfractionation. Patients with inoperable stage III NSCLC, ECOG performance status (PS) 0-2, unsuitable for concurrent chemoradiotherapy were recruited. A minimum of 2 cycles of induction chemotherapy was mandated before RT. The dose of radiation was increased until one or more of the organs at risk (OAR) met predefined constraints or the maximum dose of 79.2Gy was reached. RT was delivered twice-daily in 1.8 Gy fractions. A RT quality assurance programme was in place. The primary end point was feasibility (>80% of patients achieving >60Gy EQD2 i.e. total biologically equivalent in 2 Gy fraction), with acute/late toxicity (CTCAE version 4.0), local control and overall survival as secondary end points.
Result:
Between June 2014 and March 2016, 37 patients were enrolled from 7 UK centres. Median age = 67 years (range 46-86). Male:female ratio = 18:19. ECOG PS=0, 5 (13.51%), PS=1, 29 (78.38%), PS=2, 3 (8.11%). Stage IIIa:IIIb ratio 23 (62.2%):14 (37.8%). Out of 37 patients, 2(5.4%) failed to achieve EQD2 >60Gy due to large tumour size and inability to meet OAR constraints, they received standard RT. This was due to large tumour size and inability to meet OAR constraints. Median prescribed tumour dose was 77.4Gy (61.2 – 79.2Gy) with the maximum dose of 79.2Gy delivered to 14 (37.8%) patients. All patients completed RT as scheduled except one due to disease progression. Grade (G)3 acute toxicities included: dysphagia 1 (2.9%), dypsnoea 2 (5.7%), lung infection 3 (5.7%) and radiation oesophagitis 2 (5.7%). There were three G5 events: radiation pneumonitis, trachea-oesophageal fistula and bronchopulmonary haemorrhage, which were probably treatment related. G3 late toxicities included: fatigue 1 (2.9%), dyspnoea 3 (8.6%) and 1 (2.9%) case of late G4 lung infection. At time of analysis median follow-up was 12.8 months for 20 survivors. Overall survival and progression-free survival at 1 year was 75% and 59% respectively.
Conclusion:
In the majority, treatment intensification using isotoxic IMRT is feasible. This regime will be tested alongside other intensified treatments against standard sequential chemoradiotherapy in the ADSCAN study (ISRCTN47674500).
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MA 09.12 - Discussant - MA 09.08, MA 09.09, MA 09.10, MA 09.11 (ID 10843)
12:15 - 12:30 | Presenting Author(s): Cecile Le Pechoux
- Abstract
- Presentation
Abstract not provided
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MS 24 - Management of GGO-Containing Nodule (ID 546)
- Event: WCLC 2017
- Type: Mini Symposium
- Track: Radiology/Staging/Screening
- Presentations: 1
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MS 24.04 - Possibility of Radiotherapy for GGO-Containing Tumors (ID 7757)
15:50 - 16:10 | Author(s): Tomoki Kimura
- Abstract
- Presentation
Abstract:
Purpose/Objective(s): The popularization of computed tomography (CT) in clinical practice have increased a frequency of discovering ground-glass opacity (GGO)-containing tumor in lung. Surgery has been regarded as the general treatment including a purpose of histological examination for such tumors and its prognosis is better than that of solid-type tumors. Stereotactic body radiation therapy (SBRT) is a rapidly prevailing treatment modality in the radical treatment of mainly inoperable or high risk operable cases with stage I non-small cell lung cancer (NSCLC), but the most tumors treated with SBRT were solid type because SBRT has been performed principally for the pathology-proven tumors and it is generally difficult to acquire histological specimen in the tumors composed of GGO. Therefore a prognosis of the stage I NSCLC cases treated with SBRT when their tumors contained GGO has not been clear. The purpose of this presentation is to review the treatment outcomes for SBRT for the patients with GGO-containing tumor in our multi-institutional SBRT study group of Japanese Radiological Society (JRS-SBRTSG), and to discuss how we consider the validity of SBRT for them. Materials/Methods: GGO was defined as hazy opacity that does not obscure underlying bronchial structures or pulmonary vessels at high-resolution computed tomography. We have reviewed 174 patients (89 men, 85 women; mean age, 74 years) treated with SBRT whose lung tumor showed appearance of GGO accompanying solid component ratio to the whole tumor (S/T ratio) less than 50 % in diameter of the tumor and no metastases. SBRT was done because of the pathological proof, positive accumulation on PET study or growth of the tumor. In histology, 69 tumors were adenocarcinoma, 8 were squamous cell carcinoma, 5 were unclassified carcinoma and 92 cases were histology-unproven. The median tumor size was 23 mm (range, 9-53 mm). SBRT was performed using non-coplanar multiple static ports or dynamic arcs. A total dose of 40 -70 Gy (6-15 Gy / fraction) was prescribed in 4-10 fractions. Median biological effective dose (BED) was 108 Gy (range, 72-150 Gy) based on alpha/beta = 10 Gy. Survival, recurrence, and metastases rates were calculated using Kaplan-Meier method. Results: Median follow-up was 32 months. The 3-year local recurrence, regional lymph-node metastases, and distant metastases rates were 3.8%, 4.1%, and 8.6%, respectively. Mean S/T ratios of the subgroup with any recurrences and the subgroup with no recurrence were 22% and 4%, respectively. The rates of cause-specific and overall survival (OS) at 3 years were 98.1% and 85.6%, respectively. The 3-year OS rates of medically operable and inoperable subgroups were 96.2% and 85.6%, respectively. The 3-year OS rate of medically operable and histology-proven subgroup was 88.1%. The 3-year OS of female subgroup was 95.0% and it was significantly better overall survival rate than male. The treatment-related pneumonitis of grade 3 or more was observed in 3.4% of the total patients. Summary and Discussion: Natural course of GGO-containing tumor is much better than that of solid-type tumors. Sublober limited resection would be acceptable in the subgroup of stage I NSCLC if the tumor appears GGO for the most part because they have mostly no invasion nor metastases. SBRT is a so localized treatment only for the tumor that a study comparing SBRT versus limited surgery without regional lymph node resection might have a rationale of randomization for such candidates, however, we have to demonstrate the prognosis and risk factors regarding recurrence, survival, and late toxicity after SBRT with longer follow-up (more than 10 years). In conclusion, the outcomes of SBRT for patients with GGO-containing tumor (solid component was less than 50 % in total diameter) were excellent but some cases had local recurrence or metastases. GGO-containing in most of the tumor seldom produced local progression, lymph node metastases, or distant metastases after SBRT. Although more cases and longer follow up are mandatory, SBRT may be one of the radical treatment options for stage I NSCLC patients with GGO-containing tumor. We hope to have a further discussion regarding the validity of SBRT for them.
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P1.08 - Locally Advanced NSCLC (ID 694)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.08-006 - Phase I/II Study of Carboplatin, nab-paclitaxel, and Concurrent Radiation Therapy for Patients with Locally Advanced NSCLC. (ID 8356)
09:30 - 09:30 | Author(s): Tomoki Kimura
- Abstract
Background:
A regimen of weekly paclitaxel plus carboplatin (CBDCA) with concurrent thoracic radiotherapy is recognized as standard for patients with unresectable stage III lung cancer. Nanoparticle albumin-bound paclitaxel (nab-PTX) is a cremophor-free formulation of paclitaxel to increase solubility and intratumor drug delivery and is effective for patients with advanced NSCLC. The purpose of this study is to determine recommended dose and investigate the efficacy and safety profile of a regimen of nab-PTX plus CBDCA with concurrent thoracic radiotherapy for patients with unresectable non-small cell lung cancer (NSCLC).
Method:
Patients with unresectable stage IIIA or IIIB NSCLC, good performance status, age between 20 and 74 years, and adequate organ function, a relative volume of normal lung receiving a dose of ≥ 20 Gy (V20) ≤35% were eligible. In a phase I study (standard 3+3 design), weekly nab-PTX plus CBDCA was administered intraveneously for six weeks. Doses of each drug were planned as follows: level 1, 40/2; level 2, 50/2 (nab-PTX [mg/m[2]] / CBDCA [area under the plasma concentration time curve (AUC) mg/ml/min]). Concurrent thoracic radiotherapy was administered in 2 Gy fractions to a total dose of 60 Gy. Dose-limiting toxicity (DLT) was observed during concurrent chemotherapy and thoracic radiation and up to 28 days following the end of radiotherapy. After the evaluation of DLT, patients received an additional two cycles of consolidation chemotherapy that consisted of 3-week cycles of nab-PTX (100 mg/m[2] on Days 1, 8 and 15) plus CBDCA (AUC 6 mg/ml/min on Day 1). In a phase II study, we planned to enroll 50 patients treated with recommended dose.
Result:
In a Phase I study, 11 patients were enrolled and received treatment per protocol, with 9 evaluable for efficacy and toxicity. At nab-PTX dose level 1 (40mg/m[2]), none of 3 patients experienced DLT. At nab-PTX dose level 2 (50mg/m[2]), 1 of 6 patients experienced DLT: grade 3 leukopenia requiring a second consecutive skip in the administration of weekly nab-PTX plus CBDCA. The recommended doses (RDs) for the phase II study were nab-paclitaxel 50 mg/m[2] and CBDCA (AUC=2). From October 2015 to November 2016, a total of 52 patients were entered in the phase II portion ( median age, 66 years; age range, 48–74 years; male/female 44/8) .
Conclusion:
Concurrent chemoradiotherapy with nab-PTX 50 mg/m[2] and CBDCA AUC 2 was the recommended dose. We will report the latest efficacy and safety profile of the present therapy. Trial registration: UMIN000012719.
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P2.01 - Advanced NSCLC (ID 618)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:00 - 16:00, Exhibit Hall (Hall B + C)
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P2.01-037 - Clinical Impact of Interstitial Lung Disease on Advanced Non-Small Cell Lung Cancer (ID 9529)
09:00 - 09:00 | Author(s): Tomoki Kimura
- Abstract
Background:
The advanced non-small cell lung cancer (NSCLC) is well known of poor survival. The advanced NSCLC patients with interstitial lung disease (ILD) to be expected poorer survival. The clinical features of patients with advanced NSCLC and interstitial lung disease (ILD) is not fully elucidated, and the role of chemotherapy in advanced NSCLC with ILD remain controversial. The aim of this study was to investigate the prevalence and clinical features of advanced NSCLC patients with ILD, particularly with idiopathic pulmonary fibrosis (IPF).
Method:
We retrospectively analyzed the patients diagnosed with advanced (i.e. stage IIIB and IV) NSCLC at Tosei general hospital, from January 2008 to December 2014. The diagnosis of ILD and IPF were made according to the 2013 and 2011 research statement respectively.
Result:
A total of 899 patients of lung cancer were reviewed, 282 patients were advanced NSCLC. Of these 282 patients, 34 (12%) received the diagnosis of ILD. 22 NSCLC patients (8%) had IPF in 34 ILD. 199/248 of non-ILD NSCLC patients (80%) and 26/34 of ILD NSCLC patients (76%), which includes 17 IPF patients, received chemotherapy. 49/248 (20%) of non-ILD NSCLC and 8 (24%) of ILD NSCLC were treated with best supportive care. There was no significant difference in disease control rate and objective response rate between non-ILD NSCLC and ILD NSCLC patients (72% vs 77%, p=0.696; 33% vs 23%, p=0.271). Overall survival in patients with ILD NSCLC was significantly worse than that in non-ILD NSCLC patients (median survival, 7 months vs 10.1 months; log-rank P=0.013). In patients who received chemotherapy, ILD NSCLC patients had significantly worse survival than non-ILD NSCLC patients (median survival, 7 months vs 10.1 months; log-rank P=0.013). However, there were no significant difference in overall survivals in ILD NSCLC patients between IPF and non-IPF (median survival, IPF-NSCLC vs non-IPF NSCLC: 6.1 months vs 8.2 months; log-rank P=0.375). Among ILD NSCLC patients who received chemotherapy, we found no significant difference in overall survival between IPF NSCLC and non-IPF (median survival, 9.6 months vs 9.7 months; log-rank P=0.275).
Conclusion:
Among advanced NSCLC patients in this cohort, 12% of them had a diagnosis of ILD including 8% with IPF. Survival in advanced NSCLC patients with ILD was worse than that without ILD. We found no significant difference between ILD NSCLC patients with IPF or without IPF in survival.
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P2.07 - Immunology and Immunotherapy (ID 708)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.07-053 - A Case of Small Cell Lung Cancer Complicated During Nivolumab Administration as Second Line Treatment for Squamous Cell Lung Cancer (ID 10481)
09:30 - 09:30 | Presenting Author(s): Tomoki Kimura
- Abstract
Background:
We experience secondary cancer merging after anticancer medications. Also, as a mechanism of resistance of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors to patients with non-small cell lung cancer (NSCLC) harboring activating mutations of EGFR, conversion to small cell lung cancer is well known. However, little is known about the occurrence of secondary cancer during the use of immune checkpoint inhibitors.
Method:
We report a 71 years old man who was diagnosed small cell lung cancer during nivolumab administration as second line treatment for advanced squamous cell lung cancer.
Result:
He suffered from diffuse large B-cell Lymphoma (DLBCL) at the age of 65 years old. He received eight cycles of R-CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone combined with rituximab), and he remitted DLBCL. During his follow up by a hematologist, he pointed out a new nodule in left upper lung and small nodules in right lung with CT scan. He was diagnosed with squamous cell lung cancer by bronchoscopic biopsy. He received four cycles of carboplatin and nanoparticle albumin-bound paclitaxel combination chemotherapy as first line treatment, and he obtained partial response (PR). After 12 months of this treatment, the primary tumor re-increased and relapsed, he received nivolumab as a second line treatment. Although he obtained stable disease by nivolumab, another new lung nodule appeared in right lower lobe gradually. After 12 cycles of nivolumab, he was diagnosed with small cell lung cancer by endobronchial ultrasound transbronchial biopsy with guide-sheath. He received four cycles of combination chemotherapy with carboplatin and etoposide, and he obtained PR. We plan to resume nivolumab as the next line treatment.
Conclusion:
We reported a case of small cell lung cancer complicated during immune checkpoint inhibitor (nivolumab) administration as second line treatment for squamous cell lung cancer. In this case, monotherapy with nivolumab failed to suppress the emergence of small cell lung cancer.
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P3.12 - Pulmonology/Endoscopy (ID 728)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Pulmonology/Endoscopy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.12-001 - Lung Cancer in Patients with Interstitial Lung Disease: Clinical Characteristics and Impact on Survival (ID 7477)
09:30 - 09:30 | Author(s): Tomoki Kimura
- Abstract
Background:
Lung cancer (LC) is frequently associated with interstitial lung disease (ILD). However, there are few reports about the frequency or prognostic impact of LC in the ILD patients.
Method:
Patients diagnosed with ILD at Tosei general hospital, from January 2008 to August 2015 were retrospectively reviewed, and a total of 1070 patients with ILD had complete clinical and follow-up data.
Result:
Of the 1070 subjects, 65.8% were male, and the mean age was 68 years. Prevalence of histologically proven lung cancer was 5.6% (n=60). Of the 295 patients with idiopathic pulmonary fibrosis (IPF), 491 with Unclassifiable IIPs (UC-IP), 193 with collagen vascular disease IP (CVD-IP), 6.1% (n=18), 6.1% (n=36) and 2.6% (n=5) were affected by lung cancer. The most frequently encountered histologic types of carcinomas were Adenocarcinomas (n=23, 38%), and squamous cell carcinomas (n=21, 35%). Small-cell lung cancer was encountered for eleven cases (18%). Survival in patients with ILD-LC was significantly worse than in patients with ILD without LC (median survival, 39 months vs 96 months; P<0.001). In patients with UC-IP and with CVD-IP, survival in patients with LC was significantly worse than in patients without LC. However, there was not a significant difference in survivals in patients with IPF (median survival, 42 months vs 54.6 months; P=0.35).
Conclusion:
Prevalence of histologically proven LC was 5.6%. The most frequently encountered histologic types of carcinomas were Adenocarcinomas and squamous cell carcinomas . Survival in patients with LC was worse than without LC. However, in IPF patients, there was not significant difference.
