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P. Mitchell
Moderator of
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MA13 - Modern Technologies and Biological Factors in Radiotherapy (ID 395)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Radiotherapy
- Presentations: 12
- Moderators:M. Thomas, P. Mitchell
- Coordinates: 12/06/2016, 16:00 - 17:30, Stolz 1
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MA13.01 - Markerless Tumour Tracking during Lung Radiotherapy Using Intrafraction X-Ray Imaging (ID 5533)
16:00 - 16:06 | Author(s): C.(. Shieh, V. Caillet, M. Dunbar, P. Keall, N. Hardcastle, J.T. Booth, C. Huang, C. Haddad, T. Eade, I. Feain
- Abstract
- Presentation
Background:
Lung tumours often exhibit large and unpredictable motion that can severely compromise radiotherapy outcomes. Markerless tumour tracking can enable wide access to motion-adaptive radiotherapy, negating the risks and costs associated with implanting markers. The main barrier to markerless tumour tracking is the inferior tumor visibility on x-ray images due to overlapping anatomic structures. The aim of this study is to develop a markerless tumor tracking method for lung radiotherapy using intrafraction x-ray imaging.
Methods:
The markerless tumour tracking method (Figure1a) consists of four steps: (1) Building a tumour and anatomic model from the cone-beam CT (CBCT) acquired prior to treatment, (2) Using the anatomic model to remove the contribution of anatomic structures on intrafraction x-ray images, (3) Locating the tumour on the intrafraction 2D x-ray image via template matching using the tumour model, (4) Determining the tumour 3D position by a Kalman filter. The proposed method was retrospectively validated on (i) 11 CBCT scans from four patients with central tumours, and (ii) a kV fluoroscopic scan during a stereotactic ablative radiotherapy (SABR) treatment from the Light SABR trial (NCT02514512). Tracking errors were estimated using the motions of markers or beacons implanted near the tumours. Figure 1
Results:
Markerless tumour tracking successfully tracked tumours in all cases at every imaging angle. The mean 3D tracking error ranged from 1.8-4.1mm for the 11 CBCT scans, and was 3.0mm for the SABR case. Compared with the current standard of care, i.e. a single estimation of tumour position prior to treatment from the pre-treatment CBCT, markerless tumour tracking reduced tumour localization error by 0.9-7.9mm. Tracking errors in the left-right, superior-inferior, and anterior-posterior directions are shown in Figure1b.
Conclusion:
A markerless tumour tracking method was developed and shown to improve tumour localization accuracy in 12 lung cancer cases. This method can potentially enable wide access to motion-adaptive radiotherapy.
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MA13.02 - First-In-Human Clinical Experience with Real-Time Tumor Targeting via MLC Tracking for Stereotactic Radiotherapy of Lung Cancer (ID 5532)
16:06 - 16:12 | Author(s): J.T. Booth, V. Caillet, N. Hardcastle, C. Haddad, K. Szymura, R. O'Brien, B. Harris, T. Eade, P. Keall
- Abstract
- Presentation
Background:
MLC tracking is an emerging technology to improve tumor targeting and reduce normal tissue irradiation during radiotherapy. The purpose of this work is to present the early clinical experience from the first-in-human trial of real-time tumor targeting via MLC tracking for stereotactic ablative body radiotherapy (SABR) of lung cancer.
Methods:
Full ethics approval through an Australian ethics board has been received for recruitment of 20 patients with stage 1 lung cancer or lung metastases into the MLC tracking clinical trial (NCT02514512). To date, seven recruited patients have each had three electromagnetic beacons inserted near the tumor. An MLC tracking SABR plan was generated with planning target volume (PTV) expanded 5mm from end-exhale tumor volume (GTV). For comparison a conventional motion-encompassing SABR plan was generated with PTV expanded 5mm from a 4DCT-derived internal target volume. Treatment was delivered using a standard linear accelerator using in-house developed software to continuously adapt the MLC motion based on the Calypso beacons’ movement. Tumor motion, treated volume and reconstructed delivered dose were compared between MLC tracking and conventional motion-encompassing treatment planning.
Results:
All seven patients have been treated successfully with MLC tracking (29 successful fractions). The MLC tracking PTV for all patients has been smaller than with ITV based planning (range 12% to 41% reduction, or 2 to 18 cm[3] with MLC tracking). Subsequent reductions in normal lung dose were observed. Tumor motion was seen to vary in motion range from the planning 4DCT during treatment; significantly, larger motion was observed during treatment that exceeded standard PTV boundaries. Reconstruction of delivered treatments confirmed the accurate delivery of MLC tracking, with 100% prescribed dose delivered to the GTV.Figure 1
Conclusion:
The first treatments with MLC tracking have been successfully performed in seven lung cancer patients. Reductions in treated volumes were observed, which translated to reductions in delivered lung dose.
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MA13.03 - Analysis of Intra-Thoracic Anatomical Changes Observed in Clinical Workflow of Cone-Beam CT Guided Radiotherapy for Lung Cancer (ID 4478)
16:12 - 16:18 | Author(s): J. Belderbos, M.M.G. Rossi, M. Kwint, S.V. Beek, J. Sonke
- Abstract
- Presentation
Background:
Objectives: In lung cancer patients treated with image-guided radiotherapy we use daily Cone-Beam CT (CBCT) guidance for setup verification and to check on intra-thoracic anatomical changes (ITACs). ITACs like tumor baseline shifts, the occurrence or dissolving of an atelectasis, tumor progression or regression, pleural fluid- and infiltrative changes have been reported in 72% of lung cancer patients (Kwint M R&O 2014) during the course of irradiation. A traffic light protocol has been in use by the radiation technologists since 2010 to classify anatomical changes seen on the CBCT with anticipated different influences on the dose distribution using 4 action levels. The purpose of this study was to quantify how often the ITACs occurred in daily clinical practice and for which action level.
Methods:
All lung cancer patients irradiated in 2015 (excluding stereotactic treatments) with a dose >44 Gy were included. All patients had a daily CBCT guided online correction protocol and the traffic light action level of each CBCT was recorded. The following action levels have been defined: code red for immediate consultation with the physician before beam-on, code orange for a decision on the notification of the physician before the next fraction, code yellow to inform the physician; no action is required- and green for no change so no intervention necessary. We also analyzed the percentage of patients that received a new planning-CTscan and/or a new treatment plan.
Results:
In 2015 a total of 299 lung cancer patients were conventionally irradiated with radical intent and 5971 CBCT scans were made. Of these CBCTs 51% were scored as code green, 24% as code yellow, 24% as code orange and code red in less than 1% of the CBCTs. Forty patients (13%) had a new treatment plan, of which 34 patients (11%) had a new planning CT-scan and 6 patients (2%) had a new treatment plan on the original planning CT-scan.
Conclusion:
Image-guided irradiation for 299 conventionally fractionated lung cancer patients (>44 Gy) in 2015 revealed lTACs in 25% of the CBCT’s made and a physician’s decision on the notification was necessary. A total of 13% of the patients treated received an unscheduled adaptive treatment plan during the course of treatment. The traffic light protocol in daily clinical workflow worked well as a tool to prioritize a physician’s decision based on the ITACs seen on the CBCT images.
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MA13.04 - Discussant for MA13.01, MA13.02, MA13.03 (ID 7088)
16:18 - 16:30 | Author(s): C. Pöttgen
- Abstract
- Presentation
Abstract not provided
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MA13.05 - Nivolumab in Non-Small Cell Lung Cancer (NSCLC): The Real-Life Data (ID 5582)
16:30 - 16:36 | Author(s): E. Dudnik, M. Moskovitz, S. Daher, S. Shamai, E. Hanovich, Y. Shechtman, M. Abu-Amna, A. Zer, M. Wollner, J. Bar, O. Merimsky, A. Cyjon, T. Shochat, N. Peled
- Abstract
- Presentation
Background:
Nivolumab has been recently approved by the FDA as a 2[nd]-line treatment of NSCLC. The data regarding its efficacy in the real-life setting is lacking.
Methods:
260 consecutive patients with advanced NSCLC treated with nivolumab at five cancer centers in Israel between January 2015 and March 2016 were observed for OS and toxicity. OS was analyzed by the Cox proportional-hazards regression model.
Results:
Patient baseline characteristics: median age 67y (range 41-99); males 68%; smokers 76%; ECOG PS ≥2 46%; Non-sq/Sq/other 70%/23%/7%; KRASm/EGFRm/ALK+/other genetic aberration/none/NA 7%/5%/0%/4%/42%/42%; brain metastases 21%; liver metastases 21%; treatment (Tx) line: 1st/2nd/3rd+-line/NA 6%/64%/26%/4%. Median duration of follow-up was 4.3 mo (range 0.1-13.8); median Tx duration was 2.7 mo (range 0.1-15.5); median number of Tx cycles delivered was 6 (range 1-26). 130 (50%) patients died; median OS comprised 6.6 mo (95%CI 5.6-8.4). In univariate and multivariate analysis, the only variable which significantly correlated with OS was ECOG PS (table 1). Median OS of patients with ECOG PS 0/1 and ECOG PS ≥2 comprised 8.6 mo and 3.5 mo, respectively. Safety data is presented in table 2. Figure 1Figure 2
Conclusion:
Nivolumab has reasonable efficacy and good safety profile in the real-life setting. ECOG PS ≥2 is associated with poor prognosis.
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MA13.06 - Integrative Genomic Profiling Identifies BRAF Mutations as Novel Radiotherapeutic Targets in Adenocarcinomas of the Lung (ID 6199)
16:36 - 16:42 | Author(s): E.K. Chie, P. Gopal, M.E. Abazeed
- Abstract
- Presentation
Background:
Patients with non-small cell lung cancer (NSCLC) display a wide spectrum of oncologic outcomes, suggesting significant underlying biologic diversity. However, current radiotherapeutic management is largely homogeneous for a given stage, To advance genotype-directed radiotherapy in NSCLC, we sought to identify genetic determinants of radioresistance by leveraging cancer genomic data with a recently developed high-throughput platform for measuring radiation survival.
Methods:
We used our recently validated high-throughput proliferation assay to profile 104 lung cancer cell lines, including 89 NSCLC and 15 small cell lung cancer (SCLC) lines, for radiation survival. Survival curve analyses permitted quantitative assessment of radiosensitivity. Genomic correlates of radiosensitivity were explored by calculating the information-based similarity metric and correlating genomic parameters by accessing Oncomap data from the Cancer Cell Line Encyclopedia, the COSMIC database of the Cancer Genome Project, and The Cancer Genome Atlas.
Results:
Radiation survival across lineages reflected clinical experience regarding differential response to fractionated radiation inasmuch as lung squamous cell carcinoma and adenocarcinoma (ACA) had similar radiosensitivity, whereas SCLC and carcinoid were, respectively, more and less radiosensitive. Importantly, radiosensitivity varied more within a lineage than across lineages, with a 6-fold difference in integral survival among ACA lines. Correlation with cancer genomic data revealed BRAF mutations within the most resistant ACA lines (P = 0.0097, FDR = 0.957). A majority of the mutations identified by our analysis have been previously annotated by The Cancer Genome Atlas lung ACA dataset and all hypermorphic mutations identified were located in the highly conserved kinase domain. The majority of mutations have been known to enhance kinase activity in melanoma in a fashion analogous to the well-known BRAF V600E mutation. In line with these findings, we showed that kinase domain mutations were hypermorphic as measured by MEK and ERK1/2 phosphorylation. We also showed that exposure of wild type BRAF cells to radiation results only in a transient activation of MEK and ERK1/2. The MEK inhibitor selumetinib selectively decreased the growth of cells with kinase domain BRAF mutations and sensitized these cells to radiation.
Conclusion:
BRAF mutations are associated with radiation resistance in lung ACA. Our data nominates MEK inhibitors, a drug class currently in clinical use, as a targeted therapeutic in select BRAF-mutant lung ACA. Further investigation has the potential to yield an additional genotype-directed therapy that could impact up to 4-6% of patients with lung ACA, a frequency comparable to that of ALK rearrangements (4%) or EGFR mutations (10%).
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MA13.07 - Tumor-Targeted Radiation Promotes Abscopal Efficacy of Regionally Administered CAR T Cells: A Rationale for Clinical Trial (ID 5456)
17:24 - 17:30 | Author(s): M. Zeltsman, J. Villena-Vargas, A. Rimner, M. Mayor, D. Jones, P.S. Adusumilli
- Abstract
- Presentation
Background:
Our laboratory has demonstrated the augmented anti-tumor efficacy of intrapleurally administered cancer-antigen mesothelin (MSLN)-targeted chimeric antigen receptor (CAR) T cells (Sci Transl Med 2014), and translated the approach to a clinical trial (NCT02414269) for thoracic malignancies. We hypothesized that regionally administered MSLN CAR T cells can circulate systemically to achieve abscopal anti-tumor efficacy in an antigen-specific manner, and the abscopal efficacy can further be promoted by tumor-targeted radiation therapy (RT).
Methods:
Using optimized protocols that would permit non-necrotic, well-vascularized tumor growth in pleura, chest wall, peritoneum and flank, tumors were established in immunodeficient (NOD/SCID gamma) mice using mesothelioma or lung adenocarcinoma (LAC) cells. Tumor burden progression, MSLN-targeted CAR T-Cell accumulation at primary and distant tumors was monitored by noninvasive bioluminescence imaging (BLI) and tumor volume measurements.
Results:
A single dose of MSLN CAR T cells administered intrapleurally proliferated (Figure 1A left panel), circulated extrapleurally and accumulated at abscopal sites, including the lymph nodes, chest wall, peritoneum, and flank within 3-5 days, with subsequent T-cell proliferation at abscopal sites (Figure 1A right panel). Primary tumor-targeted, single-dose, thoracic RT prior to T-cell administration augmented T-cell accumulation as demonstrated by BLI (Figure 1B) and tumor T-cell quantification (p<0.01). In a mouse model of primary pleural, abscopal antigen-expressing and non-expressing flank tumors (Figure 1C), a single, low-dose, non-cytotoxic thoracic RT enhanced abscopal site CAR T-cell accumulation that resulted in tumor regression (p=0.01; Figure 1D). Figure 1
Conclusion:
Regionally administered mesothelin-targeted CAR T cells proliferate and eradicate the primary tumor, accumulate and demonstrate anti-tumor efficacy at abscopal sites prior to eradication of the primary tumor in an antigen-specific manner. A single low-dose primary tumor-targeted radiation therapy promotes scopal and abscopal anti-tumor efficacy. These results provide rationale to initiate a clinical trial of combination regional therapies with radiation therapy and CAR T cells.
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MA13.08 - Discussant for MA13.05, MA13.06, MA13.07 (ID 6953)
16:42 - 16:54 | Author(s): M. Pless
- Abstract
- Presentation
Abstract not provided
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MA13.09 - Serial FDG and FLT PET/CT during Curative-Intent Chemo-Radiotherapy for NSCLC Impacts Patient Management and May Predict Clinical Outcomes (ID 4257)
16:54 - 17:00 | Author(s): D. Ball, S.J. Everitt, R.J. Hicks, J. Callahan, A. Herschtal, T. Kron, N. Plumridge, M. Mac Manus
- Abstract
- Presentation
Background:
FDG-PET/CT is the gold-standard for non-small cell lung cancer (NSCLC) diagnosis, staging and tumour delineation prior to chemo-radiation therapy (CRT). FDG-PET is superior to CT for subsequent response assessment. Sequential interim metabolic and proliferative tumour response assessment with FDG and 3'-Fluorothymidine (FLT) respectively, prior to and during CRT is novel and may predict outcome.
Methods:
Patients with FDG-PET-stage I-III NSCLC who were prescribed radical chemo-RT (60 Gy in 30 fractions @ 5/wk) were enrolled. FDG and FLT PET/CT scans were performed at baseline and at weeks 2 and 4 of CRT. Intra-treatment tumour response judged by reduction in FDG and FLT uptake was categorised as complete (CR)/partial response (PR), stable (SD) or progressive disease (PD) using EORTC criteria. Overall Survival (OS) and Progression Free Survival (PFS) were measured relative to intra-treatment scan dates and plotted using Kaplan-Meier curves. Univariate Cox regressions were used to calculate associations between 1. SUVmax of baseline FDG and FLT GTV and 2. intra-treatment FDG and FLT response with patient outcomes (OS and PFS).
Results:
Sixty patients were recruited between 2009-13; male 62%; median age 66 years, adenocarcinoma (42%). Two-year OS and PFS were 0.51 and 0.26 respectively. Of 332 PET/CT scans analysed, study scans provided additional information to FDG~BL~ in 21 (35%) patients. Distant metastasis was detected in 3 patients on FLT~BL~ and in 2 patients on FDG/FLT~wk2~ changed treatment intent to palliative. Loco-regional progression during RT was observed in 5 (8%) patients, prompting larger RT fields. FLT~wk2~ response (SD vs CR/PR vs PD) was associated with OS [HR (95%CI) 1 vs 2.02 (0.87, 4.65) vs 20.09 (4, 114), p=0.012] and PFS [1 vs 2.01 (0.92,4.37) vs 32.41 (3,348), p=0.024]. Associations between the baseline FDG and FLT SUV~max ~and patient outcomes were not significant, including OS where FDG SUVmax HR [95% CI] was 1.04 [0.98, 1.10], p=0.25 and FLT SUVmax HR [95% CI] was 1.07 [0.93, 1.22], p=0.33.
Conclusion:
Tumour response on FLT~wk2~ was associated with OS and PFS. The possible association between worse clinical outcomes and early suppression of FLT uptake during CRT may be a result of repair of tumour DNA damage. Baseline FLT, FLT~wk2~ and FDG~wk2~ detected rapid distant and loco-regional progression in 10 (17%) patients prompting changes in treatment intent and RT fields.
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MA13.10 - Magnetic Resonance Imaging-Guided Delivery of Lung Stereotactic Radiotherapy Using Patient-Controlled Visual Guidance (ID 5293)
17:00 - 17:06 | Author(s): S. Tetar, F. Lagerwaard, M.A. Palacios, N. Haasbeek, O. Bohoudi, B. Slotman, A. Bruynzeel, S. Senan
- Abstract
- Presentation
Background:
Treatment-related toxicity is more common following stereotactic ablative radiotherapy (SABR) for central lung tumors, than is the case for peripheral tumors [Tekatli 2015]. Further reductions in doses to critical central structures are possible using respiration-gated SABR delivery, but insertion of fiducial markers for gating is also associated with toxicity. We describe a novel approach for clinical delivery of breath-hold gated SABR under continuous MRI-guidance.
Methods:
The MRIdian® system permits tumor visualization at 4 frames/second during treatment delivery, with radiation beam-holds whenever the target is outside a prespecified gating window. The gating procedure is as follows: a 17 second inspiration breath-hold MR scan is performed for planning before each SABR fraction (resolution 1.6×1.6×3.0 mm). Image registration is performed, and contours adapted when necessary. A 3mm PTV margin is added, and planned dose distribution recalculated for the ‘anatomy of the day’, and reoptimized. A sagittal plane is chosen for tumor tracking and gating, with a planning target margin of 3 mm. The sagittal tracking view from the MRIdian console is projected on a MR-safe monitor (Cambridge Research), and patients can continuously observe the tracking image using a mirror inside the bore.
Results:
Since May 2016, 30 fractions of MR-guided gated delivery have been performed in 5 cancer patients with 6 central tumors. All MR-based breath-hold PTV’s were smaller (mean 19.8 ± 13.3 cc) than a conventional free-breathing, motion-encompassing approach (mean 36.1 ± 21.9 cc). Plans of a single case are shown in Figure 1. Video-assisted visual feedback achieved a breath-hold gating efficiency of 52% (range 27-88%).Figure 1
Conclusion:
For high-risk SABR cases, use of MR-guided, video-assisted breath-hold gated SABR delivery constitutes a novel treatment method, allowing for minimization of mobility- and setup margins, and for improved verification of SABR delivery. Data from additional patients undergoing treatment will be presented.
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MA13.11 - Investigating the Feasibility of Establishing a Prospective Cohort of Lung Cancer Patients Following Radiotherapy with Curative Intent (ID 5602)
17:06 - 17:12 | Author(s): L. Calman, S. Taylor, R. Foster, A. Richardson, P. Smith, J. Baird, J.G. Edwards, C. Faivre-Finn, C. Foster
- Abstract
- Presentation
Background:
Worldwide lung cancer is the biggest cause of cancer mortality (Cancer Research UK, 2012) and is the UK’s second most commonly diagnosed malignancy (Macmillan Cancer Support, 2013). Early detection and treatment significantly improves five year survival rates but curative treatments can impact on patients’ health and wellbeing. To date little research has been conducted to establish the support needs and recovery patterns of health and wellbeing among lung cancer patients treated with curative intent radiotherapy. This limits our ability to identify those most at risk of poorer health and wellbeing outcomes and target services effectively to support patients better. This study assesses the feasibility of collecting patient reported outcomes measures (PROMs) and clinical details to understand recovery after curative intent radiotherapy treatment for lung cancer.
Methods:
This mixed methods study used a prospective, longitudinal cohort design. Eligible patients awaiting curative intent radiotherapy were recruited from six UK sites between October 2015 and June 2016. Questionnaires were completed before undergoing radiotherapy and 3 months later. The questionnaires included validated patient reported outcome measures, including quality of life, symptoms, social support, wellbeing and socio-demographic details. Participants’ medical details were collected by healthcare professionals (HCPs) including cancer type, stage, treatment, and comorbid conditions. Study procedures were evaluated in a qualitative process evaluation.
Results:
Of 229 eligible patients, 136 consented to the study with 73% uptake of those approached. A further 13 patients provided reduced consent to collect demographic and medical information only. Preliminary results: response rates 76% at baseline and 65% at 3 months. Of baseline responders: 59% were male; the median age was 70 years; 29% lived alone; 61% were home owner-occupiers and 20% were current smokers. Baseline EORTC-QLQ-C30 results showed a mean global health status score of 56.6 and patients were most affected by dyspnoea and fatigue with mean scores of 48.8 and 45.0. These are in line with expected scores based on reference data. To date 9 HCPs, 7 patients and 2 stakeholders have been interviewed as part of the process evaluation, study processes and procedures are deemed acceptable to participants.
Conclusion:
This study demonstrates it is feasible to recruit a cohort of lung cancer patients prospectively to assess wellbeing and patterns of recovery following radiotherapy. This novel approach to understanding lung cancer patients’ experiences of survival will enhance our ability to target appropriate and timely support to those most at risk of poorer health and wellbeing.
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MA13.12 - Discussant for MA13.09, MA13.10, MA13.11 (ID 7089)
17:12 - 17:24 | Author(s): A. Juretic
- Abstract
- Presentation
Abstract not provided
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Author of
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OA03 - Immunotherapy Checkpoint Inhibitors in Advanced NSCLC (ID 367)
- Event: WCLC 2016
- Type: Oral Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
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OA03.08 - Discussant for OA03.05, OA03.06, OA03.07 (ID 7009)
12:15 - 12:30 | Author(s): P. Mitchell
- Abstract
- Presentation
Abstract not provided
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P2.07 - Poster Session with Presenters Present (ID 468)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Nurses
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.07-008 - Victorian Comprehensive Cancer Centre Lung Cancer Clinical Audit: Collecting the UK National Lung Cancer Audit data from Hospitals in Australia (ID 4784)
14:30 - 14:30 | Author(s): P. Mitchell
- Abstract
Background:
Clinical audit may improve best practice within health. The UK National Lung Cancer Audit (NLCA) collects data from UK hospitals about care of patients with thoracic cancers. We aimed to replicate collection of the NLCA data elements from hospitals caring for patients with thoracic cancers within the Victorian Comprehensive Cancer Centre (VCCC) and associated Western and Central Melbourne Integrated Cancer Service (WCMICS).
Methods:
Retrospective audit of patients newly-diagnosed with lung cancer or mesothelioma in 2013 at 6 major VCCC or WCMICS hospitals. The objectives were: to adopt/adapt the NLCA dataset for use in the Australian context; and analyze the findings using descriptive statistics to identify variations in care. Individual data items from the NLCA were tailored to the Australian context in consultation with an expert steering committee. Data was collected from existing datasets including the Victorian Cancer Registry, Victorian Admitted Episodes Dataset and individual hospital databases. Individual medical records were audited to collect missing data.
Results:
845 patients were diagnosed during 2013. Most were aged 65-80 (55%) and 62% were male. Most had non-small cell lung cancer (81%) with 9% small cell and 2% mesothelioma. Data completeness varied greatly between fields. Headline indicators of clinical care in the table below are compared to NLCA data. A significant area of concern identified was lack of access of many patients to a specialist lung cancer nurse.
Conclusion:
Lung cancer care at participating hospitals appeared to be comparable or better to many of the headline indicators of the NLCA. However, performing the audit retrospectively resulted in significant amounts of missing data for some fields. For future audits, prospective data collection should be harmonized across sites and correlated with survival outcomes. Initiatives to improve access to specialist lung cancer nurses are urgently needed.Benchmark VCCC/WCMICS (%) NLCA-2013 (%) Patients with histological diagnosis 810/845 (96%) (75%) Patients with CT before bronchoscopy 384/492 (78%) (91%) NSCLC patients receiving PET scan 544/748 (73%) (35%) Patients with stage documented 518/845 (61%) (93%) Patients discussed at multi-disciplinary meeting 585/845 (69%) (96%) Patients seen by lung cancer nurse specialist 110/845 (13%) (84%) Lung cancer nurse specialist present at diagnosis 0/845 (0%) (65%) Patients receiving active treatment 643/845 (76%) (60%) Patients treated with surgery 242/845 (29%) (15%) Patients treated with radiotherapy 370/669 (55%) (29%) Patients treated with chemotherapy 327/638 (51%) (70%) Patients seen by specialist palliative care 179/845 (21%) (30%)
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P3.02c - Poster Session with Presenters Present (ID 472)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02c-040 - Checkmate 384: A Phase 3B/4 Dose-Frequency Optimization Trial of Nivolumab in Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) (ID 4780)
14:30 - 14:30 | Author(s): P. Mitchell
- Abstract
Background:
Nivolumab, an anti-programmed death-1 antibody, is approved for previously treated metastatic NSCLC, advanced melanoma, advanced renal cell carcinoma (RCC), and relapsed/progressive classical Hodgkin lymphoma. In two phase 3 trials (CheckMate 017 and 057), nivolumab 3 mg/kg every 2 weeks (Q2W) demonstrated superior survival and favorable safety versus docetaxel in previously treated patients with metastatic NSCLC. Clinically meaningful efficacy and a manageable safety profile have been observed in studies in melanoma (CheckMate 037, 066, and 067), RCC (CheckMate 025), and Hodgkin lymphoma (CheckMate 205 and 039). On this basis, the currently approved nivolumab dose is 3 mg/kg Q2W. Decreasing the frequency of nivolumab administration may enhance convenience and compliance while maintaining efficacy and safety in patients who receive long-term nivolumab therapy. CheckMate 384 is a phase 3B/4 trial that will evaluate the efficacy and safety of nivolumab administered at two dosing frequencies in patients with advanced/metastatic NSCLC following ~4 months’ administration of nivolumab 3 mg/kg or 240 mg Q2W.
Methods:
Adult patients with advanced/metastatic squamous or nonsquamous NSCLC and ECOG performance status 0–2 are eligible; disease can be newly diagnosed or recurrent/progressive following multimodal therapy. Patients with untreated, symptomatic brain metastases are ineligible. Patients must have tolerated and completed ~4 months (16 ± 2 weeks) of treatment with nivolumab (3 mg/kg or 240 mg) IV Q2W and achieved a complete or partial response or stable disease. After this pre-study period, patients will be randomized 1:1 to receive IV nivolumab on one of two fixed-dose regimens: 240 mg Q2W or 480 mg Q4W. Randomization will be stratified by histology and response to pre-study nivolumab treatment at randomization (complete/partial response vs stable disease). The table shows primary/secondary endpoints; the objective is to establish that nivolumab 480 mg Q4W is not inferior to 240 mg Q2W. Planned enrollment is 620 patients.Primary Endpoints Secondary Endpoints Progression-free survival rate at 6 months after randomization Progression-free survival rate at 1 year after randomization by tumor histology and by response before randomization Progression-free survival rate at 1 year after randomization Progression-free survival rate at 2 years after randomization Overall survival rate (annually, up to 5 years after randomization) Safety and tolerability, as assessed by incidence and severity of adverse events
Results:
Not applicable
Conclusion:
Not applicable
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P3.03 - Poster Session with Presenters Present (ID 473)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.03-004 - Genome-Wide Copy Number Aberrations in Mesothelioma and Its Correlation with Tumour Microenvironment including PD-L1 Expression (ID 4506)
14:30 - 14:30 | Author(s): P. Mitchell
- Abstract
Background:
Recent clinical studies have demonstrated positive correlation between tumour mutational burden and response to immune checkpoint inhibitors (CPI) in several malignancies. Although initial reports of some CPI in Malignant Mesothelioma (MM) have shown promise, the rate of somatic mutations in MM is known to be low and copy number aberrations (CNA) are the prominent genetic alterations. Using a large cohort of MM patients, we investigated CNA, PD-L1 expression and the surrounding immune infiltrates and correlated these parameters to clinicopathological features.
Methods:
Tissue microarrays (TMA) were constructed and stained with PD-L1 (E1L3N,CST, Massachusetts), CD4, CD8 and Foxp3 antibodies. PD-L1 positivity (PD-L1+) was defined as >5% membranous staining regardless of intensity and high positive as >50%. Genomic DNA was obtained from tumour cores of a representative subset (100 patients) and used for genome-wide copy number analysis. Percent genome aberrated (PGA) was computed for each sample as the total number of base pairs within altered regions, divided by the total number of base pairs in each region included in the array. Correlations of PGA, CNA profile and individual aberration (loss/gain) frequency with parameters including PD-L1 expression and survival were explored.
Results:
Amongst 329 patients evaluated, the median age was 67 years and most were male 274(83.2%). Epithelioid histology (N=203; 62.9%) was the commonest. PD-L1 positivity was seen in 41.7% with high positivity in 9.6%. PD-L1+ correlated with non–epitheloid histology (P=<0.0001) and increased infiltration with CD4, CD8 and FOXP3 lymphocytes. High PD-L1 expression correlated with worse prognosis (HR=2.37; 95%CI: 1.57-3.56; P=<0.0001) on univariate analysis but the effect was found to be time dependent. Neither PGA (P=0.57) nor CNA profile (P=0.76) were found to be associated with PD-L1 expression. After correction for multiple testing, no individual CNA count was significantly associated with PD-L1 status. Although epithelioid histology had higher PGA (P=0.04), high PGA was associated with poorer survival (HR=2.01; 95% CI: 1.24-3.26; P=0.004). This was also true when only epithelioid tumours (n=63) were considered.
Conclusion:
Increased genomic alterations in MM did not correlate with PD-L1 expression but was associated with poorer survival. High PD-L1 expression was associated with non-epithelioid MM, poor clinical outcome and increased immunological infiltrates.
