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John G Edwards



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    MA08 - Pawing the Way to Improve Outcomes in Stage III NSCLC (ID 127)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Treatment of Locoregional Disease - NSCLC
    • Presentations: 1
    • Now Available
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      MA08.02 - Durvalumab Impact in the Treatment Strategy of Stage III Non-Small Cell Lung Cancer (NSCLC): An EORTC Young Investigator Lung Cancer Group Survey (Now Available) (ID 608)

      15:15 - 16:45  |  Author(s): John G Edwards

      • Abstract
      • Presentation
      • Slides

      Background

      Stage III NSCLC represents a very heterogeneous population with extremely different treatment modalities including surgery, chemotherapy (CT) and radiotherapy (RT), mostly in combination. The results of the PACIFIC trial have now been reported in full including an overall survival (OS) benefit with durvalumab in addition to concomitant CT-RT. An electronic European survey was circulated to evaluate the impact of durvalumab in the staging and treatment strategy of stage III disease.

      Method

      A Young Investigator EORTC Lung Cancer Group survey containing 31 questions, was distributed between 31/01/18 and 31/03/19 to EORTC LCG and several European thoracic oncology societies’ members

      Result

      206 responses were analyzed (radiation oncologist: 50% [n=103], pulmonologist: 26.7% [n=55], medical oncologist: 22.3% [n=46]; 81.5% with >5 years experience in treating NSCLC). Italy (27.7%, n=57), Netherlands (22.8%, n=47), France (13.6%, n=28), and Spain (11.6%, n=24) contributed most. 83.5% (n=172) confirmed that they had access to durvalumab at the time of the survey. 97.6% (n=201) report that treatment decision is made by a multidisciplinary board. Regarding staging, 76.7% (n=158) support the need of a mediastinal pathological staging in case of suspect lymph-nodes, with a preference for EBUS/EUS (61.2%, n=126). 81.6% (n=168) treated more than half of patients with a concomitant CT-RT with the 1st cycle of chemotherapy in 39.7% (n=81). 95.1% consider durvalumab as practice changing, especially given the OS results (77.9%, n=152/195). 30% (n=119/395) will give patients concomitant CT-RT if PD-L1 >1%, and in borderline resectable cases 17.7% (n=70/395) will propose concomitant CT-RT instead of surgery. Durvalumab administration will be given regardless of PDL1 status in 13.1% (n=27) and 28.6% (n=59) would consider the possibility of a rebiopsy after CT-RT in case of negative PD-L1. 38.8% (n=80) foresee some problems with PD-L1 testing in this population due to availability of cytologic or small histologic samples. About 53.8% (n=105/195) normally will start durvalumab within 6 weeks after CT-RT and 48.5% (n=100) would also use durvalumab after sequential CT-RT

      Conclusion

      Durvalumab results are changing the treatment approach to stage III unresectable (and maybe resectable) NSCLC and planned strict adherence to the patient population as recruited to the PACIFIC study, was not demonstrated. This survey was released after the EMA approval of durvalumab and PD-L1 status seems to play a role in the treatment strategies, but surprisingly almost half of the clinicians will use durvalumab after sequential CT-RT without safety or efficacy data.

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    MS06 - An Interdisciplinary Approach to Optimal Nodal Staging (ID 69)

    • Event: WCLC 2019
    • Type: Mini Symposium
    • Track: Staging
    • Presentations: 1
    • Now Available
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      MS06.06 - The Concept of Complete Resection (Now Available) (ID 3472)

      11:00 - 12:30  |  Presenting Author(s): John G Edwards

      • Abstract
      • Presentation
      • Slides

      Abstract

      The basis of the definition of complete resection is the Union for International Cancer Control (UICC) residual tumor classification (R classification), which considers the presence or absence of tumor in the primary site, lymph nodes and distant site following treatment. It has established clinical relevance, reflects the effectiveness of treatment, may be used to determine whether further therapy is indicated and has established prognostic relevance in lung cancer [1-3]. However, there are deficiencies in that locoregional recurrence may occur after an apparent R0 resection. The Complete Resection Subcommittee was tasked by the IASLC Staging Committee in 2001 to prepare a proposal of the definition of complete resection, based on expert opinion. The proposal that was derived [4] proposed the term uncertain resection, R(un), according to the following criteria:

      An uncertain resection is defined when resection margins are proved to be free of disease microscopically, but one of the following applies:

      (a) The intraoperative lymph node evaluation has been less rigorous than systematic nodal dissection or lobe-specific systematic nodal dissection.

      (b) The highest mediastinal node removed is positive.

      (c) The bronchial margin shows carcinoma in situ.

      (d) Pleural lavage cytology is positive (R1 cy+).

      In addition, this proposal considered cases with positive pleural lavage cytology (PLC) as R(un), rather than R1, and cases with extracapsular extension of tumor in nodes removed separately, or those at the margin of the main lung specimen, were considered R1, rather than R0.

      The analysis of the proposed R Classification using the database informing the 8thEdition of the TNM was presented at the 18thWorld Conference on Lung Cancer. The predominant reason for re-classification as R(un), performed in 56% of cases, was less than systematic nodal dissection (96% of cases). Survival in the R(un) category was significantly worse than R0 in node positive cases (median survival 50 and 70 months respectively, Hazard Ratio 1.27, Figure). The status of the highest lymph node station also had prognostic significance in pN2 cases (HR 1.32). Further work, that will require the submission of high quality data to the IASLC Lung Cancer Staging Project, will investigate again the impact of the individual R factors, particularly those for which the prevalence (or data completeness) in the previous dataset was low. Participation by institutions worldwide is essential to ensure success [5].

      However, there are several aspects about R Factor assessment that require clarification. These are being considered by the R Factor Subcommittee of the Staging and Prognostic Factors Committee. A survey of the current application and interpretation of the R Classification for NSCLC has been designed. The R Factor Sub-Committee will be determining and disseminating best methodological practice for intra-operative and histopathological aspects of R factor assessment.

      figure4.jpg

      References:

      1. Brierley JD, Gospodarowicz MK, Wittekind Ch (eds). UICC TNM Classification of Malignant Tumours, 8th edition. Oxford:Wiley Blackwell; 2017; p:10-11.

      2. Wittekind C, Compton CC, Greene FL, Sobin LH. TNM residual tumor classification revisited. Cancer 2002;94:2511—9.

      3. Smeltzer MP, Lin CC, Kong FS, Jemal A, Osarogiagbon RU. Survival impact of postoperative therapy modalities according to margin status in non-small cell lung cancer patients in the United States. J Thorac Cardiovasc Surg. 2017 Aug;154(2):661-672.e10. doi: 10.1016/j.jtcvs.2017.03.085

      4. Rami-Porta R, Wittekind C, Goldstraw P. Complete resection in lung cancer surgery: proposed definition. Lung Cancer 2005;49:25—33.

      5. Giroux DJ, Van Schil P, Asamura H, Rami-Porta R, Chansky K, Crowley JJ, Rusch VW, Kernstine K; International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee. The IASLC Lung Cancer Staging Project: A Renewed Call to Participation. J Thorac Oncol. 2018 Jun;13(6):801-809. doi: 10.1016/j.jtho.2018.02.012. Epub 2018 Feb 22.

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    P2.09 - Pathology (ID 174)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Pathology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.09-15 - PD-L1 Expression and Lymphocyte Infiltration in Resected Stage IIIAN2 NSCLC: Preliminary Data from a Lung ART Ancillary Study (ID 1344)

      10:15 - 18:15  |  Author(s): John G Edwards

      • Abstract

      Background

      Patients with resectable stage IIIA N2 NSCLC, are at high risk of both systemic and loco-regional relapse following surgical resection, necessitating neo-adjuvant or adjuvant treatments. Prognostic biological markers are needed. Parameters from the immune microenvironment, including PD-L1 expression and lymphocytic infiltration, have been poorly described in this group of patients. Thus we assessed simultaneously PD-L1 expression and TIL density in a cohort of stage IIIA N2 Lung ART patients, and correlated the results with clinical and pathological features before adjuvant treatment.

      Method

      Formalin fixed paraffin-embedded tumor surgical specimens from 247 patients included in the Lung Adjuvant Radiotherapy Trial (NCT00410683) were studied. PD-L1 immunohistochemistry was performed centrally on whole slides using a validated clinical PD-L1 assay. Expression of PD-L1 in tumor cells (TC) and immune cell (IC) was scored by a trained pathologist. Morphological assessment of TIL density (percentage of tumor area) was performed on whole hematoxylin-eosin stained slides. Surgical and pathology reports were reviewed by an independent expert committee for tumor staging. Association between immune parameters and baseline clinical characteristics were assessed in exploratory analyses in order to provide insights on immune activity in resected NSCLC patients.

      Result

      PD-L1 expression in ≥1% TC, ≥50% TC, ≥1% IC, ≥10% IC was observed in 47.8%, 21.9%, 61.5%, 7.3% of patients, respectively. In univariate analysis, high PD-L1 expression in both tumor cells and immune cells for all cut points correlated strongly with a higher TIL density (p-values ≤0.001). In 41 (16.6%) patients with preoperative chemotherapy (CT), a higher TIL density was observed (mean 28.1 vs. 17.5%, p=0.0018) as compared to patients without preoperative CT, but no difference was noted for PD-L1 expression in both TC and IC,. Skip N2 metastases were associated with a higher TIL infiltration (mean 22.9% vs. 17.4% p=0.014). We found no significant correlation between PD-L1 or TIL infiltration with the number of mediastinal lymph nodes stations involved on pathological examination and with histological tumor subtypes (squamous cell carcinoma vs. adenocarcinoma).

      Conclusion

      PD-L1 expression levels in TC and IC appeared similar in stage IIIA N2 NSCLC as compared to other stages. Expression in both TC and IC strongly correlated with TIL infiltration, suggesting a prominently immune-induced expression mechanism. Preoperative chemotherapy was associated with a higher TIL infiltration but not higher PD-L1 expression. Patients with skip N2 metastases harbored a higher level of TIL density, a finding consistent with a more active immune microenvironment in this group of patients with better prognosis. These data will be subsequently updated on a larger number of patient and correlated to clinical follow-up.

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    P2.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 187)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment in the Real World - Support, Survivorship, Systems Research
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.16-02 - Randomising Patients into Trials of Thoracic Cancer Surgery: An Analysis of Patient and Cancer Team Behaviour in Practice   (Now Available) (ID 984)

      10:15 - 18:15  |  Author(s): John G Edwards

      • Abstract
      • Slides

      Background

      Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) is a multicentre trial funded by Cancer Research UK. In Stage 1 participants were invited to consent for further evaluation within the PulMiCC protocol and if eligible were offered randomisation (Stage 2) to lung metastasectomy or continued active monitoring. Noting a decreasing rate of randomisation during 2016, the Data Monitoring Committee recommended that the reasons should be investigated.

      Method

      The three most actively recruiting centres were approached and asked to provide reasons for patients in Stage 1 not being randomised and to provide data according to the fields in the first column of the table. We sought to discover who made the decision to not randomise and to establish what clinical management was then followed. If participants were deemed ineligible we asked for the reason.

      Result

      Of 155 patient participants consented into Stage 1 of the trial, and after full information and counselling during the period of assessment, 41 elected to make their own decision. The split to have or not have metastasectomy was 22:19. When the clinicians made the decision 77/78 (99%) patients had metastasectomy. Full data are given in the table. Ten patients had other pathology, nine lung cancer and one carcinoid. The protocol placed no constraint on the number of metastases but one unit set its own limits at 2-4 deeming patients outside as not eligible for randomisation but as suitable for metastasectomy.

      Reasons for not randomising a sample of 155 registered patients
      Patients elected to make their own decision 41
      Chose metastasectomy 22 (54%)
      Chose to not have metasasectomy 19 (46%)
      Clinical team overrode the trial protocol 78
      Metastasectomy 77(99%)
      Non-operative management 1 (1%)
      Primary lung neoplasia 10
      Deemed ineligible 18
      Local interpretation of the trial protocol 9
      Undecided at time of data collection 8
      Total sample 155
      Conclusion

      At trial closure, of 512 patients in Stage 1, 82% were not randomised resulting in an inconclusive result despite the efforts of many doctors and scientists and the participation of a large number of patients. In the sample of 155 drawn from the three most active centres, 78 patients deemed eligible had the decision made for them by the clinical team and of the 18 deemed ineligible, half of the reasons were not aligned with the written protocol. That means at least 56% of the patients were lost to randomisation by clinicians' decisions.The 41 patients who elected to make their own decision, to have or not have metastasectomy, did so in numbers which better reflected equipoise. The difficulty faced by clinicians in declaring uncertainty is well recognised. In PulMiCC this resulted in exclusion of many patients who had given their informed consent. Learning from this and similar experiences, later UK trials of thoracic oncology (MARS-2, VIOLETS) have recruited well after specific training in the QuinteT method for randomisation into surgical trials.

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    WS03 - ITONF Workshop: Bridging the Gaps in Thoracic Oncology Nursing - A Global Perspective (Sign Up Required) (ID 104)

    • Event: WCLC 2019
    • Type: Workshop
    • Track: Nursing and Allied Professionals
    • Presentations: 1
    • Now Available
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      WS03.06 - Panel - Innovative Nursing Care in Early Stage Lung Cancer: A Global Perspective (Now Available) (ID 3671)

      11:00 - 18:00  |  Presenting Author(s): John G Edwards

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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