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MS11 - Addressing Challenges with Surgical Resection of Lung Cancer (ID 74)
- Event: WCLC 2019
- Type: Mini Symposium
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 6
- Now Available
- Moderators:Ramon Rami-Porta, Haruhiko Kondo
- Coordinates: 9/09/2019, 15:45 - 17:30, Vancouver (2003)
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MS11.01 - Neoadjuvant Chemotherapy or Neoadjuvant Chemoradiation for Potentially Resectable Nsclc - a Surgeon's Perspective (Now Available) (ID 3500)
15:45 - 17:30 | Presenting Author(s): Ricardo Mingarini Terra
- Abstract
- Presentation
Abstract
Early studies of neoadjuvant therapy compared chemotherapy alone to surgery alone. Later, the Intergroup 0139 study utilized concurrent chemotherapy and radiation as its induction strategy, and this was the basis for adding radiation in the neoadjuvant strategy. Both strategies, neoadjuvant chemotherapy and neoadjuvant chemoradiation are considered alternatives for patients with stage IIIA non-small cell lung cancer deemed operable.
However, the toxicity of combined chemotherapy and radiation is significant. Radiotherapy has an inflammatory effect that leads to a more difficult surgical procedure and increases the number of postoperative complications. Moreover, studies comparing both strategies failed to demonstrate superiority of any of the two strategies in terms of overall survival.
On top of that, due to the limited number of radiotherapy clinics in emerging countries, radiotherapy schedules might delay the beginning of the patient’s treatment. This is also an issue to be considered when offering neoadjuvant chemoradiation.
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MS11.02 - Role of Surgery in Oligometastatic NSCLC (Now Available) (ID 3501)
15:45 - 17:30 | Presenting Author(s): C S Pramesh
- Abstract
- Presentation
Abstract
Role of Surgery in Oligometastatic NSCLC
The management of oligometastatic non-small cell lung cancer (NSCLC) is controversial. Sixty percent of patients with NSCLC present with metastatic disease; 45% of those with initially localized disease eventually develop metastatic disease. With 15% of these being oligometastatic disease, this is a significant problem. Over the last two decades, several advances have occurred which frame this question better. First, advances in imaging techniques including improved PET-CT and MRI have helped identify what is likely to be truly oligometastatic disease. Second, there have been advances in local therapy including minimally invasive and robotic approaches and perioperative management, as well as advanced radiation techniques including stereotactic ablative radiotherapy (SABR) which have made it safer. Finally, systemic therapy has undergone major changes with targeted therapy and immunotherapy making considerable progress. Most patients with metastatic NSCLC would be treated with systemic therapy with local treatment being offered only for symptomatic palliation. However, recognition of a “oligometastatic” state (where metastases are limited in number and location) has led to series of patients being treated with potentially curative intent using local treatment options, predominantly surgical.
Randomized trials to evaluate the role of surgery in oligometastatic NSCLC have not been performed, compelling a reliance on several published case series and meta analysis of these studies. These series have included highly selected patients with oligometastases, typically 1-3 metastases, most commonly located in the brain, and long term outcomes have been highly variable. Overall median five year survival of a meta analysis of studies was 23.3 percent. Five year survivals in patients treated with surgery both for the primary and the metastases range from as low as <10% to as high as 80% - this wide range is more likely a reflection of selection criteria for patients undergoing surgery rather than true variations in care. Moreover, with the lack of a true comparator arm, these results should be interpreted with caution. Important favourable prognostic factors include definitive treatment of the primary tumour, negative mediastinal nodal status and a longer disease-free interval.
Lack of well conducted prospective studies make conclusive recommendations on surgery for treatment of oligometastatic disease difficult. This is especially true now when better radiation techniques like SABR and improved outcomes with systemic treatment in selected patients with targeted and immunotherapy are available. Given the available evidence, it appears reasonable to consider surgical treatment in patients with oligometastatic disease fulfilling the following criteria: good performance status, accurately staged, with PET-CT and MRI brain showing no other sites of metastases, metachronous disease with relatively long disease free interval, negative mediastinal nodes on invasive staging, and controlled primary disease. With randomized trials being unlikely in this setting, further studies are required which prospectively collect real-world data systematically, enabling better selection criteria for patients for surgery in oligometastatic NSCLC.
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MS11.03 - Minimizing Peri-Operative Morbidity with Pneumonectomy (Now Available) (ID 3502)
15:45 - 17:30 | Presenting Author(s): Shun-ichi Watanabe
- Abstract
- Presentation
Abstract
1. Introduction
The incidence of surgical morbidity after standard pneumonectomy is reportedly 30 to 60%. Many previous studies have addressed several risk factors for surgical morbidity after pneumonectomy, including age, cardiovascular disease, recent body weight loss, high smoking index, low FEV1.0 value, chronic obstructive pulmonary disease (COPD), right pneumonectomy, massive blood loss during surgery, long operation time, neoadjuvant therapy and so on. Although surgical morbidity after pneumonectomy easily lead to patients’ mortality. When pneumonectomy seems to be inevitable to remove the tumor, surgeons sometimes intraoperatively weigh the oncological benefit of pneumonectomy against the postoperative poor QOL and high morbidity rate.
In this paper, the cause and proper management of postpneumonectomy complications are discussed to minimize peri-operative morbidity with pneumonectomy as for especially following two life-threatening categories, cardiovascular and respiratory complications.
2. Type of Complications
2.1 Cardiovascular Complications
2.1.1 Supraventricular Arrhythmias
Most of supraventricular arrhythmias present 1 to 4 days after standard pneumonectomy, but it sometimes present even a week after surgery. The incidence of supraventricular arrhythmia after pneumonectomy is reportedly 4 to 25%. Risk factors for supraventricular arrhythmias include old age, right pneumonectomy, intrapericardial pneumonectomy, major co-morbidities, and so on. For patients who are considered to be high risk for postoperative atrial fibrillation, following prevention strategies are indicated. According to the 2014 AATS guidelines, continuing β blockers in patients taking β-blockers before surgery, using intravenous magnesium supplementation if serum magnesium levels are low, using diltiazem in those patients with preserved cardiac function who were not taking β-blockers preoperatively, or using amiodarone in patients at an intermediate to high risk of developing postoperative atrial fibrillation. For hemodynamically stable patients with new onset atrial fibrillation, intravenous β-blockers or calcium channel blockers are used to reduce a heart rate down to 100 beats per minute. When patients are hemodynamically unstable, direct current cardioversion should be used. And for patients with refractory atrial fibrillation, systemic anticoagulation therapy should be used carefully weighing benefits against the risk of bleeding, especially after EPP.
2.1.2 Ischemic Heart Disease
Ischemic heart disease is known to be an independent risk factor for severe complications after pneumonectomy. The risk of a myocardial infarction after pneumonectomy is reportedly approximately 0.2 to 2.1%. Patients who are candidates for pneumonectomy should undergo careful preoperative assessment to screen for untreated coronary ischemic disease.
2.1.3 Cardiac Herniation
Cardiac herniation is a rare complication after intrapericardial pneumonectomy. Patients develop cardiac herniation when the intrathoracic pressure changes rapidly by severe cough or vomit with decubitus position. Rapid and severe hemodynamic collapse following a change in patient positioning should heighten the clinical suspicion. Chest X-ray and electric cardiogram clearly show the abnormal position of the heart (Figure 1 and 2). Correction of the cardiac herniation should be conducted immediately by re-thoracotomy after successful resuscitation. Sewing the patch to the weak tissues around the pericardium rather than the pericardium itself after intrapericardial pneumonectomy could increase the risk of cardiac herniation.
2.2 Respiratory Complications
2.2.1 Pneumonia
The incidence of pneumonia after pneumonectomy is reportedly 2 to 10%. Since pneumonia after pneumonectomy could be a life-threatening complication, care must be taken to lessen the risk of pneumonectomy. Preoperative smoking cessation, chest physiotherapy by nurses or respiratory therapists, use of enough amount of post-thoracotomy painkillers, and bronchial toilet by bronchoscope are important practical factors for minimizing the risk of pneumonia.
2.2.2 Acute Respiratory Distress Syndrome (ARDS)
According to the previous literatures, ARDS occurs in 2.7 to 3.1% of patients after standard pneumonectomy with very high mortality of 50 to 70%. Treatment of ARDS is supportive. Mechanical ventilation with small tidal volumes of less than 6 mg/kg body weight should be used to minimize the barotrauma, and the FiO2 level should be decreased to the lowest level to minimize the oxidative trauma. There has been no evidence that steroids improve the prognosis of patients developing ARDS.
2.2.3 Bronchopleural Fistula (BPF)
The incidence of BPF, which is a life-threatening complication, is reportedly 2 to 11%. The mortality of BPF after pneumonectomy is very high rate of around 40%. Risk factors for BPF includes diabetes mellitus, malnutrition, long stump (especially for left side), right pneumonectomy, preoperative chemoradiation therapy, and so on. When a patient develop the BPF, open window technique should be applied to control thoracic cavity infection which can lead the patient to death.
3. Conclusion
The mortality and morbidity rates after pneumonectomy are very high compared with those after lobectomy, simply because the patients have less cardio-pulmonary reservations. Therefore, when complications occur, surgeons must aggressively treat them not to lose the patient with taking abovementioned knowledge into consideration.
Figure 1
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MS11.04 - Surgical Resection of SCLC - Not so Obsolete Any Longer (Now Available) (ID 3503)
15:45 - 17:30 | Presenting Author(s): Gustavo Lyons
- Abstract
- Presentation
Abstract
More than 2 million new lung cancer cases were detected worldwide in 2018, and small cell lung cancer (SCLC) represents about 13-15 % of all lung cancers.
Although surgery was initially regarded as the treatment of choice for all types of lung cancer, it was abandoned for SCLC almost 30 years ago after the results of the Medical Research Council (MRC) randomized trial conducted by Fox et al. in 1973, which showed poor mean survival for the surgical group when compared to the RT group (6.5 months vs. 10 months, P = 0.04). (1) These results led to the abandonment of surgery as a standard treatment in favor of chemotherapy. Two subsequent meta-analyses revealed that the addition of thoracic radiation to systemic chemotherapy improved survival, and that has become the standard of care. (2)
After the introduction of TNM classification, investigators proposed that surgery was postulated to be indicated in limited-SCLC, particularly stage T1, N0, with 5-year survival rates of as high as 52.6% for stage 1 disease. (3) Further, surgical resection after induction chemoradiotherapy demonstrated a control of local relapse in almost 100% of the patients and 5- and 10-year survival rates for patients with stage IIB to IIA were 39% and 35%, respectively, for all patients (resected or not) and 44% and 41% for patients treated with a trimodality approach including adjuvant surgery. (4) Another argument for surgical resection is that the final histology of SCLC might reveal a component of NSCLC in 11-25% cases. (5)
In a recent series of Wakeam et al. including 2,089 patients with SCLC undergoing surgery who were matched 1:1 to those undergoing NST, surgery was associated with longer survival for stage I (median overall survival [OS] 38.6 months vs. 22.9 months), for stage II (median OS 23.4 months vs. 20.7 months), and stage IIIA (median OS 21.7 vs. 16.0 months. In analyses by T and N stage, longer OS was observed in resected patients with stage T3/T4 N0 (median OS 33.0 vs. 16.8 months, p=0.008) and node positivity (N1+ 24.4 vs. 18.3 months p=0.03; N2+ 20.1 vs. 14.6 months p=0.007). (6)
A recent meta-analysis that included a total of 41,483 patients concluded that surgical resection was associated with superior OS in stage I (HR = 0.56, 95% CI: 0.49–0.64, p< 0.001), stage II (HR = 0.75, 95% CI: 0.57–0.99, P = 0.04), and stage III diseases (HR = 0.70, 95% CI: 0.56–0.88, P = 0.002). (11) Unlike stage I disease, there is no consensus for surgery in stage II and stage IIIA SCLC.
Surgical resection is concordant with NCCN and ASCO guidelines; however, evidence shows that in the vast majority of T1 and T2 N0M0 patients, surgery is not offered in the absence of any documented contraindication. Rostadt et al., in a series of 2,442 patients with SCLC, found out that 26% were stages IA and IB and thus candidates for surgical resection, while only 38 patients (1.5%) underwent surgical therapy. (8)
CT screening identifies SCLC at an earlier stage – with better survival – than usual care and offers the hope that more SCLC patients may become long-term survivors. Austin et al. carried out a multinational study of baseline and annual repeat CT screenings of 48,037 volunteers at risk for lung cancer. (9) They found 48 SCLC cases, 92% of which were asymptomatic at diagnosis. Clinical stage was IA in 16 patients (33%), II in 5 (11%), III in 20 (42%), and IV in 7 (15%). Estimated cure rates were 36% overall and 54% for the clinical stage I cases.
Conclusions
Surgical resection is indicated in SCLC in stages I and IIA after precise staging including mediastinoscopy. Patients should receive systemic therapy after resection and mediastinal radiation therapy in cases with nodal metastases. Surgical resection in stages I and IIA SCLC is concordant with NCCN and ASCO guidelines; however, surgery is offered only in one-third of the patients in the absence of any documented contraindication. CT screening identifies SCLC at an earlier stage and offers the hope that more SCLC patients may be candidates for surgical resection and become long-term survivors. Selected cases in stages IIB and IIIA may be candidates for surgery as part of the multidisciplinary treatment.
References
1) Fox W, Scadding JG. Medical Research Council comparative trial of surgery and radiotherapy for primary treatment of small-celled or oat-celled carcinoma of bronchus. Ten-year follow-up. Lancet. 1973; 2: 63–5.)
2) Pignon JP, Arriagada R, Ihde DC, et al. A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med. 1999;341:476-484. Warde P, Payne D. Does thoracic irradiation improve survival and local control in limited-stage small-cell carcinoma of the lung? A meta-analysis. J Clin Oncol. 1992;10:890-895.)
3) Schreiber D, Rineer J, Weedon J, Vongtama D, Wortham A, Kim A, et al. Survival outcomes with theuse of surgery in limited-stage small cell lung cancer: should its role be re-evaluated? Cancer. 2010;116: 1350–57.
4) Eberhardt W, Korfee S. New approaches for small-cell lung cancer: Local treatments. Cancer Control 2003;10:289-96.
5) Asamura H, Kameya T, Matsuno Y, Noguchi M, Tada H, Ishikawa Y, et al. Neuroendocrine neoplasms of the lung: A prognostic spectrum. J Clin Oncol 2006;24:70-6.)
6) Wakeam E, Acuna SA, Leighl NB, Giuliani ME, Finlayson SRG, Varghese TK, et al. Surgery Versus Chemotherapy and Radiotherapy For Early and Locally Advanced Small Cell Lung Cancer: A Propensity-Matched Analysis of Survival. Lung Cancer. 2017; 109: 78–88.
7) Liu T, Chen Z, Dang J, Li G (2018) The role of surgery in stage I to III small cell lung cancer: A systematic review and meta-analysis. PLoS ONE 13(12): e0210001.
8) Hans Rostadt, Anne Naalsundb, Randi Jacobsena, Trond Eirik Stranda, Helge Scottc, Erik Heyerdahl Strømc, Jarle Norsteina. Should more patients have been offered surgical therapy? European Journal of Cardio-thoracic Surgery 26 (2004) 782–786)
9) Austin JH, Yip R, D'Souza BM, Yankelevitz DF, Henschke CI, International Early Lung Cancer Action Program Investigators. Small-cell carcinoma of the lung detected by CT screening: stage distribution and curability. Lung Cancer. 2012 76(3): 339-43.)
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MS11.05 - Pathological Reporting of Resected Lung Cancer - the Importance of Using Additional TNM Descriptors (Now Available) (ID 3504)
15:45 - 17:30 | Presenting Author(s): Ellen Caroline Toledo Nascimento
- Abstract
- Presentation
Abstract
Context. The anatomopathological examination aims to establish a specific diagnosis of the tumor and to provide essential information related to cancer staging, patient management and prognosis. Such information, as histologic type, lymphovascular invasion, spread through air spaces, margins, treatment effect, and TNM descriptors should be disclosed concisely, following previously defined protocols, and correlate satisfactorily with radiological exams and clinical aspects in order to allow the best management for the patient.
Histopathological (macroscopic and microscopic evaluation) combined with complementary immunohistochemical and molecular studies, provides prognostic and predictive information on tumor biology and clinical behavior. The TNM staging classifies the tumors according to the anatomic extent with an important prognostic impact. In addition, it allows the establishment of criteria for inclusion and exclusion of patients in protocol studies and subgroups of treatment, cancer registry, epidemiology and multidisciplinary management.
The T component analysis is complex because it has many elements: presence or absence of invasion, tumor size, endobronchial location, atelectasis / pneumonitis and invasion of the various anatomical structures around the lung. The determination of the largest tumor diameter requires accurate measurements since in the eighth edition TNM stage classification for lung cancer each centimeter separates tumors with different prognoses from 1 to 5 centimeters (cm). Appropriate size measurement is especially important when it comes to subsolid tumors since the correlation with the computed tomographic imaging in this context is of great value. Tumors measuring larger than 5 cm up to 7 cm (T3 in the eighth edition) had a worse prognosis than found in the seventh edition of the TNM classification. Tumors larger than 7 cm (T4 in the eighth edition) have similar prognosis to other descriptors in the T4 category. Atelectasis or pneumonitis involving the whole lung (T3 in the seventh edition) has the same prognosis for partial atelectasis / pneumonitis (T2 descriptor in the seventh edition). Endobronchial tumor location less than 2 cm from carina (a T3 descriptor in the seventh edition), but without carina involvement, had the same prognosis as the endobronchial location further than 2 cm from carina (a T2 descriptor in the seventh edition). In the eighth edition, tumors involving the main bronchus and associated with atelectasis / pneumonitis are classified as T2. On the other hand, diaphragm invasion (a T3 descriptor in the seventh edition was upstaged to T4 in the eighth edition) since it has similar prognosis of T4 tumors.
No changes to the N descriptors were proposed in the 8th TNM as the four N categories (N0, N1, N2, N3). The reassessment of the M component validated the proposed M1a category descriptors in the seventh edition and separated the distant metastases into two categories with different prognoses, M1b (single metastatic tumor in one organ), and M1c (multiple metastases in either single organ or multiple organs).
Objective. To review and discuss the 8th edition of the TNM classification of lung cancer with an emphasis on prognostic relevance and implications for the pathologist's report.
Data Sources. The review is based on the available literature.
Conclusion. The TNM (tumor-node-metastasis) classification system for lung cancer is the strongest prognostic indicator and fundamental for decisions on therapy. The eighth edition of the TNM classification of lung cancer enhances the prognostic discrimination of the different T categories and differentiates unique extrathoracic metastasis (better prognosis) from multiple metastases in one or several organs providing better definition of oligometastatic disease. Thus, the eighth edition of TNM improves the understanding of tumor anatomic extent and stratification of tumors for clinical trials.
References:
1) Rami-Porta R, Call S, Dooms C, Obiols C, Sanchez M, Travis WD et al. Lung cancer staging: a concise update. Eur Respir J. 2018;51(5).
2) Rami-Porta R, Bolejack V, Crowley J, Ball D, Kim J, Lyons G et al. The IALSC lung cancer staging project: proposals for the revisions of the T descriptors in the forthcoming eighth edition of the TNM classification for lung cancer. J Thorac Oncol. 2015;10(7):990-1003.
3) Detterbeck FC. The eighth edition TNM stage classification for lung cancer: what does it mean on main street? J Thorac Cardiovasc Surg. 2018;155(1):356-359.
4) Eberhardt WE, Mitchell A, Crowley J, Kondo H, Kim YT, Turrisi A 3rd et al. The IALSC lung cancer staging project: proposals for the revision of the M descriptors in the forthcoming eighth edition of the TNM classification of lung cancer. J Thorac Oncol. 2015;10(11):1515-1522.
5) Kay FU, Kandathil A, Batra K, Saboo SS, Abbara S, Rajiah P. Revisions to the tumor, node, metastasis staging of lung cancer (8th edition): rationale, radiologic findings and clinical implications. World J Radiol. 2017;9(6):269-279.
6) Rami-Porta R, Asamura H, Travis WD, Rusch VW. Lung cancer – major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(2):138-155.
7) Nicholson AG, Tsao MS, Travis WD, Patil DT, Galateau-Salle F, Marino M et al. Eight edition staging of thoracic malignancies: implications of the reporting pathologist. Arch Pathol Lab Med. 2018;142(5):645-661.
8) Aokage K, Miyoshi T, Ishii G, Kusumoto M, Nomura S, Katsumata S et al. Clinical and pathological staging validation in the eighth edition of the TNM classification for lung cancer: correlation between solid size on thin-section computed tomography and invasive size in pathological findings in the new T classification. J Thorac Oncol. 2017;12(9):1403-1412.
9) Butnor KJ, Beasley MB, Dacic S, Berman M, Flieder D, Jones K et al. Protocol for the examination of specimens from patients with primary non-small cell carcinoma, small cell carcinoma or carcinoid tumor of the lung. Version: Lung 4.0.0.3. 2017. https://documents.cap.org/protocols/cp-thorax-lung-2017-protocol-4003.pdf
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MS11.06 - The Impact of Prehabilitation on Patients Having Lung Cancer Surgery (Now Available) (ID 4060)
15:45 - 17:30 | Presenting Author(s): David Sanchez-Lorente
- Abstract
- Presentation
Abstract not provided
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PL02 - Presidential Symposium including Top 7 Rated Abstracts (ID 89)
- Event: WCLC 2019
- Type: Plenary Session
- Track:
- Presentations: 11
- Now Available
- Moderators:Giorgio Vittorio Scagliotti, Ramon Rami-Porta
- Coordinates: 9/09/2019, 08:00 - 10:15, Barcelona (2005)
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PL02.02 - Lung Cancer Screenee Selection by USPSTF Versus PLCOm2012 Criteria – Interim ILST Findings (Now Available) (ID 2804)
08:00 - 10:15 | Presenting Author(s): Stephen Lam | Author(s): Renelle Myers, Mamta Ruparel, Sukhinder Kaur Atkar-Khattra, Emily Stone, Renne Manser, Annette Maree McWilliams, Paul Fogarty, David CL Lam, John Yee, John Mayo, Christine Dorothy Berg, Sam Janes, Kwun M Fong, Martin Tammemagi
- Abstract
- Presentation
Background
The National Lung Screening Trial showed that lung cancer screening of high-risk individuals with low dose computed tomography can reduce lung cancer mortality by 20%. Critically important is enrolling high-risk individuals. Most current guidelines including the United States Preventive Services Task Force (USPSTF) and Center for Medicare and Medicaid Services (CMS) recommend screening using variants of the NLST eligibility criteria: smoking ≥30 pack-years, smoking within 15 years, and age 55-80 and 55-77 years. Many studies indicate that using accurate risk prediction models is superior for selecting individuals for screening, but these findings are based on retrospective analyses. The International Lung Screen Trial (ILST) was implemented to prospectively identify which approach is superior.
Method
ILST is a multi-centred trial enrolling 4000 participants. Individuals will be offered screening if they are USPSTF criteria positive or have PLCOm2012 model 6-year risk ≥1.5%. Participants will receive two annual screens and will be followed for six years for lung cancer outcomes. Individuals not qualifying by either criteria will not be offered screening, but samples of them will be followed for lung cancer outcomes. Outcomes in discordant groups, USPSTF+ve/PLCOm2012-ve and PLCOm2012+ve/USPSTF-ve, are informative. Numbers of lung cancers and individuals enrolled, sensitivity, specificity and positive predictive values (PPV) of the two criteria will be compared.
Result
As of March 2019, ILST centers in Canada (British Columbia), Australia, Hong Kong, and the United Kingdom had enrolled and scanned 3673 individuals. Study results are summarized in Figure 1.
Conclusion
Interim analysis of ILST data, indicates that classification accuracy of lung cancer screening outcomes support the PLCOm2012 criteria over the USPSTF criteria. The PLCOm2012 criteria detected significantly more lung cancers. Individuals who are USPSTF+ve and PLCOm2012-ve appear to be at such low baseline risk (0.2%) that they may be unlikely to benefit from screening.
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PL02.03 - Early Detection of Cancer of the Lung Scotland (ECLS): Trial Results (Now Available) (ID 557)
08:00 - 10:15 | Presenting Author(s): Frank Sullivan | Author(s): Stuart Schembri
- Abstract
- Presentation
Background
Scotland has one of the highest rates of lung cancer in the world -- 460 men and 340 women in 100 000 are diagnosed with lung cancer every year. In the UK, survival from lung cancer is poor with less than 9% of patients still alive at five years after diagnosis, due primarily to the late stage of presentation. The EarlyCDT®-Lung Test is a novel Autoantibody(AAB) diagnostic test for the early detection of lung cancer allowing stratification of individuals according to their risk of developing lung cancer. The Test measures seven AABs; p53, NYESO-1, CAGE, GBU4-5, HuD, MAGE A4 & SOX2. It identifies 41% of lung cancers with a high specificity of 90%. This compares to CT scanning, which when used
Method
alone as a prevalence screening test, identifies 67% of lung cancers developing over the following 12 months, but has a low specificity of around 49%. The autoantibodies detected in the test have not been shown to vary with age, gender and ethnicity. The primary research question is: ‘Does using the EarlyCDT®-Lung Test, followed by X-ray and CT scanning, to identify those at high risk of lung cancer reduce the incidence of patients with late-stage lung cancer (III & IV) or unclassified presentation (U) at diagnosis, compared to standard clinical practice?’
An RCT in 12,208 participants
Participants
Asymptomatic adults aged 50 to 75 who had a high risk of developing lung cancer over the next 24 months were eligible to participate. 5 290/12 209 (43.3%) of the subjects lived in the most deprived quintile with the mean age at recruitment 60.5 years and the mean pack years smoked 38.2 . Participants were allocated to intervention or comparison group during the recruitment visit using a web-based randomization system. Test positive patients were offered a chest X-ray followed by a non-contrast thoracic CT scan. If the initial CT scan revealed no evidence of lung cancer then subsequent CT scans were offered 6 monthly for 24 months. Individuals with abnormalities were followed up over the study period or referred for clinical care as appropriate. All individuals entering the study were followed up via record linkage including the Scottish Cancer Registry.Control
UK standard clinical practice
OUTCOMES
Primary
The difference, at 24 months after randomisation, between the rates of patients with stage III, IV or unclassified lung cancer at diagnosis in the intervention arm & control arm;
Secondary
Eight further measures including mortality, economic and psychological.
Power
Using an assumption of 600/100,000 for late stage lung cancer in the population studied and acknowledging that recruitment is over a 2 year period the study has a power of 80% to detect a 35% reduction associated with the use of the EarlyCDT-Lung test to identify cases.Analysis
Result
Cox proportional hazards models were used to estimate the hazard ratio of the rate of late stage lung cancer in the intervention arm compared to the control arm. Participants who were lost to follow up were censored. The models adjust for age, gender, smoking history, and practice. Random cluster effects were included rather than fixed effects for practices. Comparisons of proportions were carried out using chi square tests. Fisher’s Exact test was used if the numbers of events are small.
127 lung cancers were diagnosed in the study period (56 in the intervention group and 71 in the control arm). 9.8% of the intervention group had a positive EarlyCDT-Lung test and 3.4% (n=18) of these were diagnosed with lung cancer in the study period.
Conclusion
Fewer participants in the intervention group were diagnosed at a late-stage (III & IV) compared with the control group (33 vs 52). The rate of late-stage (III & IV) lung cancer diagnosis in the intervention group was 58.9% and in the control group was 73.2%. The number of early-stage (I & II) lung cancers diagnosed in the intervention group was higher than in the control group (23 vs 19). The EarlyCDT-Lung test was positive for 12 of
the 23 early cancers (sensitivity 52.2%, 95% CI 30.6% to 73.2%) and for 6 of the 33 late-stage cancers (sensitivity 18.2%, 95% CI 7.2% to 35.5%).
The study was not powered to detect a difference in mortality, however there was a non significant trend suggesting fewer deaths in the intervention arm compared to the control (87 vs 108 respectively). Similar results were noted relating to lung cancer-specific mortality (17 vs 24).
Our results show that the combination of the EarlyCDT-Lung followed by CT imaging in those with a positive blood test, results in a significant decrease in late stage diagnosis of lung cancer and may decrease all cause and lung cancer specific mortality. We shall continue follow up of all participants’ lung cancer and mortality outcomes at 5 years using Scottish ISD (Information Services Division) data to study these effects further.
Blood-based biomarker panels, such as the EarlyCDT-Lung test, may have an important role in future lung cancer screening programmes. Further studies including ones to establish the ideal testing frequency are required.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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PL02.04 - Blood MicroRNA and LDCT Reduce Unnecessary LDCT Repeats in Lung Cancer Screening: Results of Prospective BioMILD Trial (Now Available) (ID 907)
08:00 - 10:15 | Presenting Author(s): Ugo Pastorino | Author(s): Mattia Boeri, Stefano Sestini, Federica Sabia, Mario Silva, Paola Suatoni, Carla Verri, Anna Cantarutti, Nicola Sverzellati, Giovanni Corrao, Alfonso Marchianò, Gabriella Sozzi
- Abstract
- Presentation
Background
The National Lung Screening Trial (NLST) showed that lung cancer (LC) screening by three annual rounds of low-dose computed tomography (LDCT) reduced lung cancer mortality, and MILD trial provided additional evidence that extended intervention beyond 5 years, with annual or biennial rounds, enhanced the benefit of screening. The new bioMILD trial tested the additional value of blood microRNA (miRNA) assay at the time of LDCT on a large series of volunteers, with the aim of targeting next LDCT intervals on the basis of individual risk profile.
Method
BioMILD trial offered a lung cancer screening program combining LDCT and blood microRNA assay, to heavy smokers (current or former ≤10 years) aged 50-75 years (clinicaltrials.gov ID: NCT02247453). At baseline, LDCT and miRNA were tested independently with blind evaluation, choosing a 3-year interval for the next repeat in participants with double negative LDCT and miRNA.
Result
From January 2013 to March 2016, bioMILD prospectively enrolled 4,119 volunteers at Istituto Nazionale Tumori of Milan. The median age was 60 years, median pack-years 42, current smokers 79% and females 39%. According to baseline LDCT and miRNA profile, 2384 subjects (58%) with double negative LDCT and miRNA (2neg) were sent to 3-year LDCT repeat, 1526 (37%) with positive miRNA or indeterminate/positive LDCT (1pos) and 209 (5%) with positive miRNA and indeterminate/positive LDCT (2pos) were sent to annual or shorter LDCT repeat, depending on LDCT results. After four screening runs (LDCT 0/1/2/3), a total of 115 LCs were diagnosed (2.8%). Cumulative LC incidence was significantly different in the three groups: 0.6% for 2neg subjects, 3.8% for 1pos and 20.1% for 2pos (p<0.0001); LC mortality was 0.1%, 0.6% and 3.8% respectively (p<0.0001). Interval cancer incidence, proportion of stage I and resected LC were not statistically different among groups.
Conclusion
The combination of microRNA assay and LDCT is a valuable and safe tool to assess individual risk profile and reduce unnecessary LDCT repeats in lung cancer screening. Targeting LDCT intervals on individual risk profile did not cause any detrimental effects on LC detection or mortality.
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PL02.05 - Discussant - PL02.02, PL02.03, PL02.04 (Now Available) (ID 3912)
08:00 - 10:15 | Presenting Author(s): Harry J. de Koning
- Abstract
- Presentation
Abstract not provided
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PL02.06 - In Hospital Clinical Efficacy, Safety and Oncologic Outcomes from VIOLET: A UK Multi-Centre RCT of VATS Versus Open Lobectomy for Lung Cancer (Now Available) (ID 1257)
08:00 - 10:15 | Presenting Author(s): Eric Lim | Author(s): Tim Batchelor, Joel Dunning, Michael Shackcloth, Vladimir Anikin, Babu Naidu, Elizabeth Belcher, Mahmoud Loubani, Vipin Zamvar, Tim Brush, Lucy Dabner, Rosie Harris, Dawn Phillips, Chloe Beard, Holly McKeon, Sangeetha Paramasivan, Daisy Elliott, Alba Realpe Rojas, Elizabeth Stokes, Sarah Wordsworth, Jane Blazeby, Chris Rogers, T Violet Trialists
- Abstract
- Presentation
Background
VATS is currently the most popular form of access for lung cancer resection in the UK. However, there is limited comparative information from high quality randomised controlled trials and no information on early oncologic outcomes for quality assurance for a minimal access approach. VIOLET is the largest randomised trial conducted to date to compare clinical efficacy, safety and oncologic outcomes of VATS versus open surgery for lung cancer.
Method
VIOLET is a parallel group randomised trial conducted across 9 UK thoracic surgery centres. Participants with known or suspected primary lung cancer were randomised in a 1:1 ratio to VATS (one to four ports) or open lobectomy. Randomisation was stratified by surgeon. Patients within clinical stage cT1-3, N0-1 and M0 using TNM 8 with disease suitable for VATS or open surgery were eligible to join the trial. We report on early outcomes in the period from randomisation to hospital discharge after surgery.
Result
From Jul 2015 to Feb 2019, 2,109 patients were screened to randomise 503 participants to VATS (n=247) or open (n=256) lobectomy. The mean age (SD) was 69 (8.8) years and 249 (49.5%) were male. Baseline clinical T category was cT1 333 (67.3%), cT2 125 (25.2%), cT3 37 (7.5%) with cN0 466 (94%) and cN1 30 (6%). Lobectomy was undertaken in 221 (89.5%) patients randomised to VATS and 232 (90.6%) patients randomised to open surgery. The in-hospital mortality rate was 1.4% (7/502) and the conversion rate from VATS to open was 5.7% (14/246) with the main reasons listed as pleural adhesions (n=4) and bleeding (n=4).
There were no differences in R0 resection; which was 98.8% (218/223) in the VATS group and 97.4% (228/234) in the open group; P=0.839 or in nodal upstaging from cN0/1 to pN2 disease which was observed in 6.2% (15/244) of the VATS group and 4.8% (12/252) of the open group; P=0.503.
The median (visual analogue) pain score was 4 (interquartile range, IQR 2 to 5) in both groups on day one with 3 (1 to 5) in the VATS group and 4 (2 to 5) in the open group on day two.
A significant reduction of overall in-hospital complications was observed in patients receiving VATS at 32.8% (81/247) compared to open 44.3% (113/255) surgery; P=0.008 without any difference in serious adverse events between the two groups, which was 8.1% (20/247) for VATS and 7.8% (20/255) for open surgery; P=0.897.
Patients randomised to VATS had a shorter median (IQR) length of stay of 4 (3 to 7) versus 5 (3 to 8) days compared to patients randomised to open surgery, P=0.008.
Conclusion
In early stage lung cancer, VATS lobectomy is associated with significantly lower in-hospital complications and shorter length of stay compared to open lobectomy. This was achieved without any compromise to early oncologic outcomes (pathologic complete resection and upstaging of mediastinal lymph nodes) nor any difference in serious adverse events in the early post-operative period.
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PL02.07 - Discussant - PL02.06 (Now Available) (ID 3913)
08:00 - 10:15 | Presenting Author(s): Jessica S Donington
- Abstract
- Presentation
Abstract not provided
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PL02.08 - Registrational Results of LIBRETTO-001: A Phase 1/2 Trial of LOXO-292 in Patients with RET Fusion-Positive Lung Cancers (Now Available) (ID 964)
08:00 - 10:15 | Presenting Author(s): Alexander Drilon | Author(s): Geoffrey R Oxnard, Lori Wirth, Benjamin Besse, Oliver Gautschi, Shao Weng Daniel Tan, Herbert H. Loong, Todd Bauer, Yu Jung Kim, Atsushi Horiike, Keunchil Park, Manisha Shah, Caroline McCoach, Lyudmila Bazhenova, Takashi Seto, Marcia Brose, Nathan Pennell, Jared Weiss, Ignacio Matos, Nir Peled, Byoung Chul Cho, Yuichiro Ohe, Karen L Reckamp, Valentina Boni, Miyako Satouchi, Gerald S Falchook, Wallace Akerley, Haruko Daga, Tomohiro Sakamoto, Jyoti D Patel, Nehal Lakhani, Fabrice Barlesi, Mark Burkard, Viola W. Zhu, Victor Moreno, Jacques Medioni, Marc Matrana, Christian Rolfo, Dae Ho Lee, Hovav Nechushtan, Melissa Johnson, Vamsidhar Velcheti, Makoto Nishio, Ryo Toyozawa, Kadoaki Ohashi, Lucy Song, Ji-Youn Han, Alexander Spira, Filippo Guglielmo Maria De Braud, Kristoffer Staal Rohrberg, Shinji Takeuchi, Jun Sakakibara-Konishi, Saiama Waqar, Hirotsugu Kenmotsu, Frederick Wilson, Binoj Nair, Elizabeth Olek, Jennifer Kherani, Kevin Ebata, Edward Zhu, Michele Nguyen, Luxi Yang, Xin Huang, Scott Cruickshank, Stephen Michael Rothenberg, Benjamin J Solomon, Koichi Goto, Vivek Subbiah
- Abstract
- Presentation
Background
No targeted therapy is currently approved for patients with RET fusion-positive non-small cell lung cancer (NSCLC). LOXO-292 is a highly selective RET inhibitor with activity against diverse RET fusions, activating RET mutations and brain metastases. Based on initial data from LIBRETTO-001, LOXO-292 received FDA Breakthrough Designation for the treatment of RET fusion-positive NSCLC in August 2018.
Method
This global phase 1/2 study (87 sites, 16 countries) enrolled patients with advanced RET-altered solid tumors including RET fusion-positive NSCLC (NCT03157128). LOXO-292 was dosed orally in 28-day cycles. The phase 1 portion established the MTD/RP2D (160 mg BID). The phase 2 portion enrolled patients to one of six cohorts based on tumor type, RET alteration, and prior therapies. The primary endpoint was ORR (RECIST 1.1). Secondary endpoints included DoR, CNS ORR, CNS DoR, PFS, OS, safety and PK.
Result
As of 17-June 2019, 253 RET fusion-positive NSCLC patients were treated. The primary analysis set (PAS) for LOXO-292 registration, as defined with the US FDA, consists of the first 105 consecutively enrolled RET fusion-positive NSCLC patients who received prior platinum-based chemotherapy; 58 patients (55%) also received prior anti PD-1/PD-L1 agents. The majority of PAS responders have been followed for ≥6 months from first response. Of the remaining 148 patients, 79 had previously been treated with platinum-based chemotherapy, 55 did not receive prior platinum-based chemotherapy and 14 did not have measurable disease at baseline.
Conclusion
Among PAS patients, the investigator-assessed ORR was 68% (95% CI 58-76%, n=71/105, 2 PRs pending confirmation). Responses did not differ by fusion partner or the type or number of prior therapies, including chemotherapy, anti PD-1/PD-L1 agents and multikinase inhibitors with anti-RET activity. The median DoR was 20.3 months (95% CI 13.8-24.0) with a median follow-up of 8 months; as evidenced by the wide confidence interval, this DoR estimate is not statistically stable due to a low number of events (16 of 69 confirmed responders). The intracranial ORR was 91% (n=10/11: 2 confirmed CRs, 8 confirmed PRs) for patients with measurable brain metastases at baseline.
The ORR in efficacy evaluable treatment naïve RET fusion-positive NSCLC patients was 85% (95% CI 69-95%, n=29/34, 7 PRs pending confirmation). In the safety data set of all 531 patients, 5 treatment-related AEs occurred in ≥15% of patients: dry mouth, diarrhea, hypertension, increased AST and increased ALT. Most AEs were grade 1-2. Only 9 of 531 (1.7%) patients discontinued LOXO-292 for treatment-related AEs.
LOXO-292 had marked antitumor activity in RET fusion-positive NSCLC patients and was well tolerated. These data will form the basis of an FDA NDA submission later this year.
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PL02.09 - National Lung Matrix Trial (NLMT): First Results from an Umbrella Phase II Trial in Advanced Non-Small Cell Lung Cancer (NSCLC) (ID 2282)
08:00 - 10:15 | Presenting Author(s): Gary William Middleton | Author(s): Sanjay Popat, Peter Fletcher, Yvonne J. Summers, Alastair Greystoke, David Gilligan, Judith Cave, Noelle O'Rourke, Alison Brewster, Elizabeth W. Toy, James Spicer, Joshua Stephen Savage, Rowena Sharpe, Timothy A. Yap, Charles Swanton, Lucinda Billingham
- Abstract
Background
Oncogene-addicted NSCLC can achieve substantial clinical benefit with single-agent targeted therapy. Seeking to extend this paradigm to other more genetically complex NSCLC, we report first results of NLMT, an umbrella phase II trial whereby a bespoke next-generation sequencing screening panel (Stratified Medicine Programme 2) stratifies NSCLC patients to rationally selected targeted therapies. Uniquely we present results across the entirety of the platform to enable an assessment of the potential to further stratify medicine in advanced NSCLC. Novel methodology is used to ensure that the integrity of this ongoing platform trial is not jeopardised.
Method
NLMT uses a Bayesian adaptive design to screen currently 8 targeted drugs for signals of activity in 22 molecularly defined cohorts. For single agents, pre-specified clinically relevant outcomes are either median progression-free survival (mPFS) >3 months or objective response rate (ORR) and/or durable clinical benefit rate at 24 weeks (DCBR) >30%. Target recruitment for each cohort is 30 with futility analyses at 15. Recruitment continues in 19 cohorts. We report posterior probabilities (PP) of a clinically relevant outcome for closed cohorts and Bayesian predictive probability of success (PPoS) given observed data for open cohorts. This novel approach provides insight into the drug-biomarker combinations that have the strongest potential for further research.
Result
Over a 4 year period to end of March 2019, NLMT has recruited 286 patients from >4000 screened. Of 6 palbociclib cohorts (all proficient Rb): mPFS in KRAS mutation (n=30) is 5.8 months (PP>0.99); CDKN2A loss/non-squamous (n=27) passed its interim analysis; we predict >75% PPoS, given current data, in CDKN2A loss/squamous (n=16) and CCND1 amplification (n=13). Data for crizotinib show >90% PPoS in ROS1 gene fusions (n=8) and MET exon 14 skipping mutation (n=8), with less clear signal for MET amplification (n=9). Responses to selumetinib/docetaxel in NF1 mutation (n=16) warrant continuation. Recruitment to vistusertib was halted at interim for LKB1 single mutation (ORR=0/15, PP=0.003; DCBR=1/15, PP=0.026), but DCBR in LKB1/KRAS double mutation (n=23) warrant continuation. 4 cohorts receive capivasertib (n=22): data in PIK3CA amplifications (n=9) indicate <15% PPoS.
Conclusion
These first results from the largest stratified medicine dataset in NSCLC indicate further molecular stratifications could benefit from targeted therapies. Reporting interim outputs for all cohorts will allow reappraisal of the global stratified medicine strategy in cancer.
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PL02.10 - Discussant - PL02.08, PL02.09 (Now Available) (ID 3914)
08:00 - 10:15 | Presenting Author(s): Robert C. Doebele
- Abstract
- Presentation
Abstract not provided
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PL02.11 - Overall Survival with Durvalumab Plus Etoposide-Platinum in First-Line Extensive-Stage SCLC: Results from the CASPIAN Study (Now Available) (ID 2265)
08:00 - 10:15 | Presenting Author(s): Luis Paz-Ares | Author(s): Yuanbin Chen, Niels Reinmuth, Katsuyuki Hotta, Dmytro Trukhin, Galina Statsenko, Maximilian J. Hochmair, Mustafa Özgüroğlu, Jun Ho Ji, Oleksandr Voitko, Artem Poltoratskiy, Santiago Ponce, Francesco Verderame, Libor Havel, Igor Bondarenko, Andrzej Kazarnowicz, György Losonczy, Nikolay V. Conev, Jon Armstrong, Natalie Byrne, Norah Shire, Haiyi Jiang, Jonathan Goldman
- Abstract
- Presentation
Background
Extensive-stage (ES)-SCLC is a recalcitrant disease associated with a median OS of ~10 months following etoposide-platinum (EP); new treatments that prolong survival are needed. CASPIAN (NCT03043872) is an open-label, phase 3 study of durvalumab (anti-PD-L1), ± tremelimumab (anti-CTLA-4), combined with EP as first-line treatment for patients with ES-SCLC. Here we report results for durvalumab + EP (D+EP) versus EP from a planned interim analysis.
Method
Patients with previously untreated ES-SCLC (ECOG PS 0/1) were randomised (1:1:1) to durvalumab 1500 mg + EP q3w; durvalumab 1500 mg + tremelimumab 75 mg + EP q3w; or EP q3w. Patients in immunotherapy arms received up to 4 cycles of EP followed by maintenance durvalumab until progression. Patients in the EP arm received up to 6 cycles of EP and prophylactic cranial irradiation (PCI), at the investigator’s discretion. Investigator’s choice of cisplatin or carboplatin was allowed across all arms and was a stratification factor at randomisation. The primary endpoint was OS. Data cutoff: 11 March 2019.
Result
268 patients were randomised to D+EP and 269 to EP. Baseline characteristics were well balanced between arms. In the EP arm, 56.8% of patients received 6 cycles of EP. At the interim analysis, D+EP significantly improved OS compared to EP with a HR of 0.73 (95% CI, 0.591-0.909; p=0.0047); mOS 13.0 versus 10.3 months, respectively. 33.9% of patients were alive at 18 months with D+EP versus 24.7% with EP. Secondary endpoints of PFS and ORR were also improved with D+EP compared to EP: PFS HR 0.78 (95% CI, 0.645-0.936); mPFS 5.1 versus 5.4 months; 12-month PFS rate 17.5% versus 4.7%; investigator-assessed ORR (RECIST v1.1; unconfirmed) 79.5% versus 70.3% (odds ratio, 1.64 [95% CI, 1.106-2.443]). The incidences of grade 3/4 AEs (61.5% versus 62.4%) and AEs leading to discontinuation (9.4% each) were similar between arms; the incidence of haematological toxicities was numerically higher in the EP arm. The durvalumab + tremelimumab + EP arm continues blinded to final analysis.
Conclusion
The addition of durvalumab to EP as first-line treatment for ES-SCLC significantly improved OS (27% reduction in risk of death) versus a robust control arm that permitted up to 6 cycles of EP and PCI. Of note, this chemo-immunotherapy regimen offers flexibility in platinum choice (carboplatin or cisplatin), reflecting current clinical practice for this challenging disease. No new safety signals were identified.
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PL02.12 - Discussant - PL02.11 (Now Available) (ID 3915)
08:00 - 10:15 | Presenting Author(s): Myung-Ju Ahn
- Abstract
- Presentation
Abstract not provided
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PL04 - Food for Thought in the Management of Thoracic Malignancies (ID 91)
- Event: WCLC 2019
- Type: Plenary Session
- Track: Advanced NSCLC
- Presentations: 4
- Now Available
- Moderators:Daniel SW Tan, Ramon Rami-Porta
- Coordinates: 9/10/2019, 16:15 - 17:00, Barcelona (2005)
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PL04.01 - Epidemiology and Clinical Characteristics of Lung Cancer in Women (Now Available) (ID 3595)
16:15 - 17:00 | Presenting Author(s): Enriqueta Felip
- Abstract
- Presentation
Abstract
"Non applicable"
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PL04.02 - What Does Survivorship Mean in the World of Immunotherapy (Physical and Financial)? (Now Available) (ID 3596)
16:15 - 17:00 | Presenting Author(s): Michelle Turner
- Abstract
- Presentation
Abstract
With improvements in diagnostic, therapeutic, and supportive therapies, the number of cancer survivors
continues growing with over 20 million cancer survivors worldwide and an estimated 2/3 of adults with
a cancer diagnosis who are anticipated to be alive in 5 years1. Due to this increase in survivors, major
medical societies such as American Society of Clinical Oncology (ASCO), Institute of Medicine (IOM), and
the Society for Immunotherapy of Cancer’s (SITC) have highlighted the need for strategies to improve
the ongoing care of survivors and survivorship plans.2
The 4 basic tenets of a survivorship plan are surveillance, prevention, intervention and coordination.
Surveillance is aimed at monitoring for recurrence, second cancers, and long term toxicities, prevention
of these sequelae if possible, intervention if they are found, and lastly coordination between hospital
and community‐based doctors is essential for this plan to be effective.3 These needs are typically
communicated to the patient’s general practitioner (GP)/primary care physician (PCP) by a “care plan”
that outlines the patient’s oncology treatment course, potential long‐term toxicity, the
frequency of follow up visits, scans and links to community resources.
New cancer therapies such as immunotherapy has resulted in significantly improved overall survivals in
many advanced cancers, including those that had formerly been considered refractory.6,7,8 However, the
short‐, intermediate‐, and long‐term complications of these therapeutic agents are still being identified.
Immune‐mediated events, for example, can occur immediately after therapy initiation or even up to two
years post treatment as a consequence of overstimulation of the immune system leading to
autoimmunity with the potential for permanent or long‐term sequelae.4,5
References:
1. https://cancercontrol.cancer.gov/ocs/statistics/statistics.html
2. https://www.canceradvocacy.org/
3. Denlinger, CS et. Al. Survivorship: Introduction and Definition. J Natl Compr Canc Netw. 2014 Jan; 12(1): 34–45.
4. Sheela S, Kim ES, Mileham KF. Moving away (finally) from doublet therapy in lung cancer: immunotherapy and KEYNOTE‐189J Thorac Dis. 2018 Sep;10(9):5186‐5189.
5. Weber JS, Hodi FS, Wolchok JD, et al. Safety Profile of Nivolumab Monotherapy: A Pooled Analysis of Patients With Advanced Melanoma. J Clin Oncol 2017; 35:785.
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PL04.03 - The Relevance of an International Database for the Study of Thymic Neoplasms (Now Available) (ID 3597)
16:15 - 17:00 | Presenting Author(s): Vanessa Bolejack
- Abstract
- Presentation
Abstract
Introduction
Until the 8thedition of the AJCC/UICC TNM classification of malignant tumours went into effect, no official stage classification was available for thymic malignancies. Some classification systems had been proposed but were generally developed from a limited number of patients and not usually tested in an independent dataset. The system developed by Dr. Akira Masaoka in 1981 did undergo external validation and was widely adopted. However, the adoption of these proposed systems in different institutions and regions was hampered by a lack of uniform nomenclature and varying interpretations of definitions. The current (8thedition) TNM stage classification for thymic malignancies endorsed by AJCC and UICC was informed by a database with 10,808 cases of thymic malignancies from 105 sites worldwide, compiling cases contributed by ITMIG (including patients from North and South America, European, and Korean (KART) and Chinese (ChART) institutions), Japan (JART), and Europe (ESTS) with funding and coordination by IASLC and Cancer Research and Biostatistics (CRAB), with the specific intent of developing a TNM based staging system for these malignancies.
Methods and materials
The IASLC Stating and Prognostic Factors Committee - Thymic Domain (SPFC-TD) conducted a web-based cross-sectional survey to assess the implementation of the 8thEdition TNM staging system in the thoracic community. The survey was sent to the major thymic organizations (ITMIG, ESTS, KART, ChART, RYTHMIC, JART) in addition to IASLC membership. A new database to inform the 9thedition TMN staging system is under development to provide updated follow-up from the institutions contributing to the 8thedition database, add additional institutions, and add new cases collected prospectively.
Results
According to the survey results, the TNM stage classification of thymic tumors has gained a reasonable acceptance in the scientific community, while the Masaoka stage system remains widely employed. An increased attention to the N descriptor seems to have been incorporated. There is high awareness of the new staging system. The current efforts of the Thymic Domain of the IASLC Staging and Prognostic Factors Committee focus on expanding and updating the database used for the 8thedition to further refine the stage definitions and includes updated follow-up on patients from Turkey, the ESTS, JART, ChART and KART, plus data collected prospectively from ChART.
Conclusion
The database created to inform the 9thedition of TNM staging for thymic malignancies will allow for refinement and adjustment of the 8thedition system and attempt to address any perceived deficiencies of the current system. An overview of the current state of the database will be presented at the meeting in Barcelona.
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PL04.04 - Prognostic Factors in Malignant Pleural Mesothelioma (Now Available) (ID 3598)
16:15 - 17:00 | Presenting Author(s): Michaela B Kirschner
- Abstract
- Presentation
Abstract
Malignant pleural mesothelioma (MPM) is a disease for which we are facing difficulties and challenges at many levels from diagnosis over treatment selection and prediction of treatment response to prediction of the prognosis of individual patients. Besides the necessities to obtain an accurate and early diagnosis and to be able to predict the response to a specific treatment, it is equally important to be able to estimate the overall prognosis of a patient as this will also affect treatment decisions.
Looking at the research efforts of the last two decades, we see an abundance of studies investigating prognostic markers for MPM, yet to date the most reliable predictors of disease outcome are still the clinical and pathological parameters, which have been used in the past. Probably the most accurate prognostic factor for MPM is the histopathological subtype, with epithelioid MPM being associated with the best prognosis followed by the biphasic subtype and sarcomatoid histology. In addition, it is well recognised that patients presenting with less advanced disease, of younger age and female gender are generally doing better. Some of these factors were combined with additional proposed predictors of outcome into scoring systems suggested by the European Organization for Research and Treatment of Cancer (EORTC, [1]) and the Cancer and Leukemia Group B (CALGB, [2]). Both scores have been subsequently validated and still hold true today, over 20 years later.
Since then, many studies have attempted to identify additional prognostic biomarkers. One area of extensive research is the investigation of changes in blood cell ratios, which can be linked to the inflammatory and/or nutritional status of the patients [3, 4]. In terms of inflammation-related indicators of poor outcome, elevated C-reactive protein (CRP), a high neutrophil-to-lymphocyte ratio, and a low lymphocyte-to-monocyte ratio (LMR) have been proposed. Some of these inflammatory markers have also been combined with factors reflecting the nutritional status of patients. For example, has the combination of CRP and albumin been suggested to have prognostic value, as shown in the CRP-to-albumin ratio (CAR) and the modified Glasgow Prognostic Score (mGPS). Another proposed combination is that of albumin and lymphocytes into the Prognostic Nutritional Index (PNI). Additionally, radiological factors, such as tumour volume or pleural thickness measured by CT or MRI alone or as part of prognostic scores (e.g. in combination with other factors such as in the multimodality prognostic score [5]), as well as radiomics approaches have shown prognostic potential [6]. While many of these proposed prognostic factors are often routinely collected during standard clinical work-up and blood tests, prospective testing in a clinical setting has yet to be attempted.
A second area of extensive research in the last decade has been molecular factors, namely the expression of proteins, genes, and microRNAs [3]. Initially, the majority of studies focused on the potential prognostic role of protein expression in tumour tissue. Here, rather frequently, the expression of tyrosine kinases such as epidermal growth factor receptor (EGFR) and c-Met has been investigated, due to the additional potential of targeting those using tyrosine kinase inhibitors. In addition, many cell cycle and apoptosis-related proteins such as p21, p53, survivin or PTEN were evaluated, but in many cases these proteins did not reach significance in multivariate analyses, highlighting that they do not represent independent markers. Other proteins, such as ERCC1 and TS, the target of the antimetabolite drug pemetrexed, did not show consistent results between various studies, hence none of these proteins are used routinely in the clinic. On the level of gene expression, already 15 years ago a 4-gene signature was proposed, which was subsequently independently validated, but never in a prospective fashion. In addition to gene expression, microRNAs have also been proposed to hold prognostic value, but again, independent validation is thus far lacking.
While many candidate prognostic biomarkers have been proposed, these tend to be dependent on the histological subtype, and the identification of factors predictive of outcome within the individual histological subgroups of MPM patients remains a major challenge. However, with more genetic profiling of larger datasets becoming available also in MPM, investigators have started to address this issue. By aiming to genetically subclassify pathologically purely epithelioid or sarcomatoid tumours, this resulted in the C1/C2 classification [7] and the e-score and s-score classification [8], as well as the 4 cluster iCluster classification generated based on TCGA data [9]. Besides providing potential novel prognostic factors, the molecular characterization of MPM can also provide us with urgently needed deeper insights into the biology of the different subgroups of MPM, which is likely to allow us to identify novel treatment targets together with respective markers predictive of response.
Nevertheless, these exciting recent findings remain to be independently validated, most importantly in a prospective fashion. A closer look at the literature of the last two decades, however, shows us that rather than aiming at validation of proposed prognostic factors, we are inclined to identify novel candidates. In order to move these promising novel candidates from the bench to the bedside, international collaboration to increase cohort sizes as well as prospective validation will be crucial.
References:
1. Curran, D., et al., J Clin Oncol, 1998. 16(1): p. 145-52.
2. Herndon, J.E., et al., Chest, 1998. 113(3): p. 723-31.
3. Davidson, B., Hum Pathol, 2015. 46(6): p. 789-804.
4. Yamagishi, T., et al., Lung Cancer, 2015. 90(1): p. 111-7.
5. Opitz, I., et al., J Thorac Oncol, 2015. 10(11): p. 1634-41.
6. Armato, S.G., 3rd, et al., Lung Cancer, 2019. 130: p. 108-114.
7. de Reynies, A., et al., Clin Cancer Res, 2014. 20(5): p. 1323-34.
8. Blum, Y., et al., Nat Commun, 2019. 10(1): p. 1333.
9. Hmeljak, J., et al., Cancer Discov, 2018. 8(12): p. 1548-1565.
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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
- Moderators:Simon Ekman, Helena A Yu
- Coordinates: 9/08/2019, 15:15 - 16:45, Tokyo (1982)
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MA08.09 - Results of Trimodality Therapy for Patients with cN2 Lung Cancer Diagnosed by Video-Assisted Mediastinoscopic Lymphadenectomy (VAMLA) (Now Available) (ID 1295)
15:15 - 16:45 | Author(s): Ramon Rami-Porta
- Abstract
- Presentation
Background
After a properly performed transcervical lymphadenectomy, invasive restaging of the mediastinum is unnecessary because there is no material left for a new biopsy. Therefore, when video-assisted mediastinoscopic lymphadenectomy (VAMLA) is used at primary staging, the only parameters to select patients for lung resection after induction therapy are: the stability of the primary tumor and the absence of extrathoracic disease assessed by PET-CT. The aim of this study is to analyze the results of those patients with cN2 NSCLC diagnosed by VAMLA who underwent trimodality treatment in terms of feasibility and survival.
Method
Prospective observational single-center study of 250 patients (206 men; median age, 65.7; range, 42-86) with NSCLC cN0-1 (by PET-CT) who underwent VAMLA from 01-2010 to 12-2017. Patients with cN2 diagnosed by VAMLA who underwent trimodality treatment (cisplatin-based chemotherapy concomitant with radical radiotherapy [mean 54Gy, range 40-70Gy] plus lung resection) were analyzed. Follow-up was completed in March 2019. Median follow-up for surviving patients was 39.5 months (range, 8-108). Survival analysis was performed by the Kaplan-Meier method; the log-rank test was used for comparisons. Patients who died within 90 days after resection were excluded from survival analyses. A p-value of less than 0.05 was considered significant. The IBM SPSS Statistics for Mac, version 20.0 was used.
Result
The rate of unsuspected N2-3 disease in the whole series was 14.5% (35 patients). 28 patients out of 35 were considered for trimodality treatment. The results of restaging based on the PET-CT were: disease progression in 8 (28.5%) (mostly distant metastases), and stability of the primary tumor or partial response in 20 patients (71.5%). Of 20 patients without progression, 13 (46.5%) underwent lung resection; the remaining 7 were considered unfit for surgery. Three- and 5-year survival rates for those candidates for chemoradiotherapy (n=28) were: 91.7% and 80.2%, respectively, for patients in whom complete lung resection was achieved; 34.3% and 0%, respectively, for those considered unfit for surgery; and 19% and 0%, respectively, for those with progression after chemoradiotherapy (p < 0.0001)(Figure 1).
Conclusion
The use of VAMLA to select patients for trimodality treatment is feasible. Based on the results obtained (high rate of unsuspected cN2 diagnosed by VAMLA and prolonged survival of those patients in whom the trimodality treatment was accomplished), VAMLA should be included in the current staging algorithms, especially for those tumors with intermediate risk of N2 and normal mediastinum by PET-CT.
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MA15 - Usage of Computer and Molecular Analysis in Treatment Selection and Disease Prognostication (ID 141)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Pathology
- Presentations: 1
- Now Available
- Moderators:John Le Quesne, Noriko Motoi
- Coordinates: 9/09/2019, 15:45 - 17:15, Tokyo (1982)
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MA15.10 - Stromal Markers of Activated Tumor Associated Fibroblasts Predict Poor Survival and Are Associated with Necrosis in Non-Small Cell Lung Cancer (Now Available) (ID 2212)
15:45 - 17:15 | Author(s): Ramon Rami-Porta
- Abstract
- Presentation
Background
Tumor associated fibroblasts (TAFs) are essential contributors of the progression of non-small cell lung cancer (NSCLC). Most lung TAFs exhibit an activated phenotype characterized by the expression of α-SMA and fibrillar collagens. However, the prognostic value of these activation markers in NSCLC remains unclear.
Method
We conducted a retrospective multicentric study of the prognostic value of the standard markers of activated fibroblasts. For this purpose, we conducted a quantitative image analysis of α-SMA immunostaining and picrosirius red staining of fibrillar collagens imaged by bright-field and polarized microscopy, respectively, using tissue microarrays with samples from 220 surgical patients, which elicited a percentage of positive staining area for each marker and patient.
Result
Kaplan-Meier curves showed that all TAF activation markers were significantly associated with poor survival, and their prognostic value was independent of TNM staging as revealed by multivariate analysis, which elicited an adjusted increased risk of death after 3 years of 129% and 94% for fibrillar collagens imaged with bright-field (p = 0.004) and polarized light (p = 0.003), respectively, and of 89% for α-SMA (p = 0.009). We also found a significant association between all TAF activation markers and tumor necrosis, which is often indicative of hypoxia, supporting a pathologic link between tumor desmoplasia and necrosis/hypoxia.
Conclusion
Our findings identify patients with large histologic coverage of fibrillar collagens and α-SMA+ TAFs to be at higher risk of recurrence and death, supporting that they could be considered for adjuvant therapy. Moreover it supports that antifibrotic drugs aiming to target tumor fibrosis may be an effective therapeutic approach to improve survival in NSCLC.
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OA12 - Profiling the Multidisciplinary Management of Stage III NSCLC (ID 144)
- Event: WCLC 2019
- Type: Oral Session
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Now Available
- Moderators:Dirk De Ruysscher, Bartomeu Massuti
- Coordinates: 9/09/2019, 15:45 - 17:15, Seoul (2007)
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OA12.07 - Radicality of Lymphadenectomy in Lung Cancer According to Surgical Approach. Results from the Spanish Group of Video-Assisted Thoracic Surgery (Now Available) (ID 1062)
15:45 - 17:15 | Author(s): Ramon Rami-Porta
- Abstract
- Presentation
Background
The minor standard of systematic nodal dissection (SND) in lung cancer surgery, which is the minimum recommended by the Union for International Cancer Control, requires the resection/sampling of, at least, 3 mediastinal (including subcarinal station) and 3 hilar/intrapulmonary lymph nodes (LN). The objective of this study is to analyze differences in intraoperative LN assessment in patients with surgically treated non-small cell lung cancer (NSCLC) according to surgical approach (open vs VATS), from the results of the Spanish Group of Video-Assisted Thoracic Surgery (GEVATS) database.
Method
Prospective multicenter cohort study of anatomic pulmonary resections (n=3533) performed from 20/12/16 to 20/03/18. Exclusions criteria were: indications different from NSCLC, previous lung cancer, synchronous tumors and induction therapy. Patients who did not meet the criteria for SND but had no nodal involvement were coded as pathologic (p)Nx (instead of pN0). Corresponding tests for homogeneity were performed. Multiple logistic regression analysis was used to determine the odds ratio (OR) and 95% confidence interval (95%CI). Stata/SE vs 13 statistical package was used for data analysis. Significance was considered when p<0.05.
Result
2532 patients were analyzed (1801 men [71.1%]; median age: 67 years). SND was performed in 65%, with a median of LN resected/sampled of 7 (IQR 4-12) and a rate of pN2 of 9.5%. Table1 summarizes results from bivariate analysis.Independent risk factors for thoracotomy at multivariate analysis (OR; 95%CI) were: squamous cell carcinoma vs adenocarcinoma (1.3; 1.04-1.68), staging mediastinoscopy (2.8; 1.83-4.22), LN resected (1.02; 1.00-1.04), SND (1.4; 1.07-1.8), tumour >3cm (1.8; 1.5-2.2), central tumour (2.5; 2.0-3.1); pN1 (1.5; 1.1-2.1) and pN2 (1.6; 1.1-2.3). A significantly higher proportion of nodal upstaging was observed in thoracotomy group: from cN0 to pN1/pN2, and from cN1 to pN2 (table1).
Conclusion
The intensity of lymphadenectomy in GEVATS was superior in the thoracotomy approach. Therefore, intraoperative lymph node evaluation performed at VATS should improve to have better prognostic information and indicate adjuvant therapy.
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OC01 - Opening Ceremony (ID 82)
- Event: WCLC 2019
- Type: Opening Ceremony
- Track:
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/07/2019, 19:00 - 20:30, Barcelona (2005)
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OC01.01 - Welcome Addresses (Now Available) (ID 3551)
19:00 - 20:30 | Presenting Author(s): Ramon Rami-Porta
- Abstract
- Presentation
Abstract not provided
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OC01.03 - Conference Presidents Announce New Things at WCLC 2019 (Now Available) (ID 3554)
19:00 - 20:30 | Presenting Author(s): Ramon Rami-Porta
- Abstract
- Presentation
Abstract not provided
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P1.17 - Treatment of Early Stage/Localized Disease (ID 188)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.17-08 - mRNA Expression Level of Receptor Tyrosine Kinases and Non-Receptor Tyrosine Kinases as a Recurrence Risk in Resected Adenocarcinoma of the Lung (ID 786)
09:45 - 18:00 | Author(s): Ramon Rami-Porta
- Abstract
Background
The profile of receptor tyrosine kinases (RTK) and non-receptor tyrosine kinases (non-RTK) is crucial for tumor genesis and therapeutic strategy in several types of cancer. We previously reported that elevated mRNA expression level of some RTKs/non-RTKs (AXL, CDCP1, STAT3, YAP1) were related to poorer prognosis in lung adenocarcinoma patients receiving EGFR-TKI. The prognostic impact of RTKs/non-RTKs is unclear in early-stage lung cancer. This study aims to explore the usefulness of RTK and non-RTK to detect the risk of recurrence in resected NSCLC, especially in EGFR mutant adenocarcinoma.
Method
We retrospectively collected pathologic N0-2 adenocarcinoma cases resected in Japanese and Spanish institutions. mRNA expression levels of RTK or non-RTK (STAT3, YAP1, AXL, CDCP1, MET, SHP2, and EGFR) in surgical specimens were evaluated and the impact of expression level on recurrence-free survival (RFS) was compared. The oncological significance on RTK or non-RTK was validated in vitro.
Result
Among enrolled 268 cases, 100 cases (37.3%) harbored EGFR mutation. Forty-five EGFR mutation positive cases recurred and cases with higher mRNA expression level of EGFR showed worse RFS. In addition, higher expression of CDCP1 or SHP2 indicated poorer RFS in EGFR mutation positive cases. In vitro, combination of SHP099 (SHP2 inhibitor) and osimertinib showed synergism in EGFR mutation positive cell line (Combination index was 0.62).
Conclusion
Higher expression of SHP2 and CDCP1 is potential risk of recurrence in EGFR mutant lung adenocarcinoma. The synergism of SHP2 inhibitor plus EGFR-TKI suggests that the expression level of SHP2 is involved in tumorigenesis and is a promising predictor for recurrence in EGFR mutant lung adenocarcinoma.
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PR01 - Press Conference (ID 92)
- Event: WCLC 2019
- Type: Press Conference
- Track:
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/07/2019, 16:00 - 17:30, CC7.1 A&B
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PR01.02 - Welcome from Co-Chairs (Now Available) (ID 3600)
16:00 - 17:30 | Presenting Author(s): Ramon Rami-Porta
- Abstract
- Presentation
Abstract not provided
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