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Jose Ramirez
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EP1.01 - Advanced NSCLC (ID 150)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.01-41 - Feasibility of EBUS-TBNA Cytologies for an Extensive Assessment of Predictive Biomarkers in Lung Cancer (Now Available) (ID 1640)
08:00 - 18:00 | Author(s): Jose Ramirez
- Abstract
Background
Clinical guidelines support the determination of several driver genes as well as PD-L1 to drive treatment decisions in non-small cell lung cancer (NSCLC). Endobronchial-ultrasound transbronchial needle aspiration (EBUS-TBNA) cytology specimens are useful for the initial diagnosis of NSCLC, although its capacity to provide enough material for a complete genotyping remains controversial. The aim of this study is to determine the yield of EBUS for a comprehensive multiplex genotyping in patients (pts) with suspected NSCLC.
Method
In this single-center, ongoing, prospective study, samples from mediastinal lymph nodes were obtained from pts undergoing EBUS-TBNA for lung cancer diagnosis/staging. Following malignant confirmation and appropriate cell content by rapid on-site evaluation, the study sample was obtained and formalin-fixed paraffin-embedded (FFPE). Three analytes were evaluated (DNA/RNA/protein). DNA and RNA were extracted and analyzed by Oncomine Solid Tumour panel (22 genes) and a customized nCounter panel (ALK, ROS; RET, NTRK, METDe14). Tumor Proportion Score (TPS) for PD-L1 protein expression was evaluated by an expert pathologist and scored into <1% (negative), 1-49% (weakly positive) and 50% (high).
Result
Twenty-five pts with NSCLC have been included and cytology samples of 20 of them molecularly characterized (5 still in progress). Overall, cytological analysis of EBUS-TBNA yield a complete characterization for the three analytes (DNA/RNA/protein) in 15 pts (75%). EBUS-TBNA sampling was sufficient for both, Nanostring and Oncomine evaluation, in a total of 18 pts (90%): 15 patients (83%) had any alteration detected by oncomine (TP53 61% [11/18],KRAS 44% [8/18], EGFRe 195.5% [1/18], BRAF V600E 5,5% [1/18], DDR2 5.5% [1/18], STK11 11% [2/18]) and 1 pt (5.5 %) by nanostring (METDex14). A total of 19 samples were sufficient for PD-L1 expression scoring (95%). TPS for PD-L1 expression was negative in 8 pts (42%), week in 4 (21%) and high in 7 pts (37%). Overall, half of the pts evaluated (10/20) would be potential candidates for an upfront personalized treatment strategy using targeted agents or immunotherapy.
Conclusion
EBUS-TBNA is a promising alternative source of material for NSCLC genotyping and allows the identification of pts candidates for personalized therapies.
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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): Jose Ramirez
- 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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MS17 - Pathology of the Future (ID 80)
- Event: WCLC 2019
- Type: Mini Symposium
- Track: Pathology
- Presentations: 1
- Now Available
- Moderators:Erik Thunnissen, Teh-Ying Chou
- Coordinates: 9/10/2019, 14:30 - 16:00, Interlaken (1988)
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MS17.02 - Major Pathological Evaluation in Neoadjuvant Immunotherapy (Now Available) (ID 3538)
14:30 - 16:00 | Presenting Author(s): Jose Ramirez
- Abstract
- Presentation
Abstract
The pathologists play different roles in the care of cancer patients. The main part of this activity is to make the diagnosis of the tumor type, followed by the support to the clinicians in the staging of the patient.
In the group of patients that receive Chemotherapy (CT) and / or Radiotherapy (RT) before surgery, the pathologist has to evaluate the results of these treatments by evaluating the tumor bed and the response of the lung.
There is a lot of experience in the literature referred to the different types of pathological response to lung cancer treatment after the use of either CT or RT. There are guidelines for the pathologists in order to give an objective evaluation of the treatment results (1). All of them ask the pathologists to evaluate the percentage of viable tumor cells, necrosis and stromal reaction. We can also find different attempts to find molecular markers useful for predicting survival after these traditional treatments (2).
In order to have an objective evaluation of the lung cancer patients after CT in 2014 emerged the concept of Major Pathological Response (MPR) as a possible predictor of overall survival (3). This term was applied to describe those patients with a viability of 10% of the tumor cells after neoadjuvant CT. In this report, they propose the MPR as a surrogate endpoint. Since that, the concept of MPR has been used in different reports and assays, becoming a usual parameter for patients with lung resections after receiving chemotherapy.
The percentage of viable cells became an important data that has to be evaluated with accuracy in order to avoid subjective results. One of the best ways is to use any of the commercial systems to make measurements on the slides. In our department, we use digital slides to get objective and reproducible data for this type of evaluation.
The recent implementation of immunotherapy (IT) for NSCLC that is being applied to an increasing number of patients all over the world makes it necessary to study deeply its morphological effects over de tumor in lung specimens. As most of the patients will never go to the operating room, it becomes important to be aware of the limited knowledge that we have so far.
There are some reports comparing the effects of the traditional chemotherapy with immunotherapy. One of these studies shows that the pathologist should look for the same features that are routinely evaluated in the cases after CT (4). The pathologist might evaluate the classic features (viable cells, necrosis and stromal reaction) and other characteristics such as macrophages, cholesterol clefts, lymphoid aggregates, giant cells and neovascularization. In this review, they did not find important differences between the type of morphological changes in both types of treatment, so they propose to use the same parameters in CT and in IT
A recent report proposes the concept of Immuno related Pathological Response Criteria (irPRC) (5). They pay attention to the Immune activation with dense lymphoid infiltrate, macrophages and tertiary lymphoid structures as the main characteristics. They also evaluate the massive tumor cell death with destructive features such as cholesterol clefts and those indicative of tissue repair with neovascularization and fibrosis.
Last year a review collected different assays done with neoadjuvant IT in patients with resectable lung cancer (6). There is no enough experience in these special groups of patients, as today the IT is given only to advanced lung carcinoma patients.
Conclusions: At the present time there are no guidelines for the evaluation of lung tissues after IT. The pathologists have to be aware of the effects of these new biological treatments for lung cancer patients, in order to give as much information as possible in the short number of cases that are seen in the real clinical situation. The previous experience in resected lungs after neoadjuvant therapy is not enough to evaluate the cases after IT. The data obtained from these lung specimens have to give more information in order to improve the knowledge of the effects of these new therapies.
References:
1. Pataer A, Kalhor N, Correa AM et al. Histopathologic Response Criteria Predict survival of Patients with Resected Lung Cancer After Neoadjuvant Chemotherapy. J Thorac Oncol. 2012;7: 825–832.
2. Pataer A, Shao R, Correa AM et al. Major pathologic response and RAD51 predict survival in lung cancer patients receiving neoadjuvant chemotherapy. Cancer Medicine 2018; 7(6):2405–2414.
3. Hellman MD, Chaft JE, William NW et al. Pathologic response after neoadjuvant chemotherapy in resectable non-small cell lung cancers: proposal for the use of “major pathologic response” as a surrogate endpoint. Lancet Oncol. 2014 January ; 15(1): e42–e50.
4. Weissferdt A, Sepesi B, Pataer A et al. Pathologic assessment following neoadjuvant immunotherapy or chemotherapy demonstrates similar patterns in non-small cell lung cancer (NSCLC). Ann Oncol 2018: 29(S8).
5. Cottrell TR, Thompson ED, Forde PM et al. Pathologic features of response to neoadjuvant anti-PD-1 in resected non-small-cell lung carcinoma: a proposal for quantitative immune-related pathologic response criteria (irPRC). Annals of Oncology 2018; 29: 1853–1860.
6. Owen D, Chaft JE. Immunotherapy in surgically resectable non-small cell lung cancer. J Thorac Dis 2018; 10(S3): 404-411.
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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-61 - Preliminary Report of a Multidisciplinary Task Group for the Study of Immune-Mediated Pulmonary Toxicity (ID 1647)
10:15 - 18:15 | Author(s): Jose Ramirez
- Abstract
Background
Immunotherapy (IO) is now the standard of care for many tumor types. However, it is not free of risks, being pulmonary toxicity one of the most relevant immune-related adverse event due to its severity. Differential diagnosis with other pulmonary complications such as infections or tumor dissemination further complicates its management.
Method
In order to raise awareness, gather information, and to discuss early management strategies in patients (pts) with immune-related interstitial lung disease (irILD), in 2017 we created a multidisciplinary task group comprised of pneumologists, pathologists, oncologists and radiologists. We herein report the main features of the first series of pts treated with IO who subsequently developed ILD, prospectively identified from a tertiary University Hospital over a period of two years (2017-2019), focusing on clinical presentation, radiological patterns, outcomes and therapeutic intervention.
Result
We identified a total of 23 pts with suspicion of irILD. Patients mainly received programmed cell death-1 (PD-L1) inhibitors (61%). Main characteristics are summarized in Table 1. ILD occurred more often in males, and former or current smokers (91%), with a median age of 62 years. The most common radiological pattern was the presence of ground-glass opacities (87%), followed by consolidations (61%). Forty-eight percent of the cases had grade 3 severity according to the Common Terminology Criteria for Adverse Events (CTCAE). Thirteen of the patients (57%) underwent a fibrobronchoscopy during the diagnostic period and a specific microorganism was isolated from BAL in three cases (13%) (Aspergillus fumigatus, cytomegalovirus and herpes type 1 virus). Ten pts (43%) underwent transbronchial biopsies being focal organizing pneumonia and desquamative changes the most common pathological patterns observed. Twenty patients (87%) received prednisone (1mg/kg/day) and thirteen of them (57%) also received antibiotic treatment.
ConclusionPatients (%)
Mean age (years)
61.63 ± 12.35
Gender
Male
19 (83%)
Female
4 (17%)
Smoking history
Current
2 (9%)
Never
7 (30%)
Former
14 (61%)
Type of cancer
Lung
8 (35%)
Kidney
5 (22%)
Skin
4 (17%)
Others*
6 (26%)
* Others: haemathologic, bladder, liver, sigma, urothelial, timic.
Immunotherapy
Nivolumab
8 (35%)
Pembrolizumab
6 (26%)
Durvalumab
2 (9%)
Others*
7 (30%)
* Others: Atezolizumab, Nivolumab+Ipilimumab, Atezolizumab+Daratumumab, Atezolumab+Bevacizumab, CX-072, Nivolumab/Nivolumab+Ipilipumab, Avelumab.
Immuno-mediated pulmonary toxicity is a rare but severe complication that carries a significant mortality. Due to their complexity, multidisciplinary approach is required to provide an adequate treatment and to guarantee early intervention.
