Virtual Library
Start Your Search
Domenico Galetta
Author of
-
+
EP1.01 - Advanced NSCLC (ID 150)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 4
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
-
+
EP1.01-01 - Atrial Resection Without Cardiopulmonary Bypass for Lung Cancer (Now Available) (ID 2778)
08:00 - 18:00 | Presenting Author(s): Domenico Galetta
- Abstract
Background
Results of resection of lung cancer invading left atrium (T4atrium) without cardiopulmonary bypass (CPB) remain controversial. We reviewed our experience analyzing surgical results and postoperative outcomes.
Method
Patients who underwent extended lung resection for T4atrium without CPB between 1998 and 2018 were retrospectively reviewed using a prospective database.
Result
Forty-four patients were collected (34 men, median age, 63 years). Twenty-five patients underwent preoperative mediastinal staging and 27 received induction treatment (IT). Lung resection included 40 (90.9%) pneumonectomies, 3 (6.8%) lobectomies and one bilobectomy (2.3%). Pathological nodal status was N0 in 10 patients (22.7%), N1 in 18 (40.9%), and N2 in 16 (36.4%). Four patients receiving IT had complete pathological response (9.1%). Eight patients (18.2%) had microscopic tumor evidence on atrial resected margins. Mortality was nil. Major complication rate was 11.4%: one BPF, one cardiac herniation, and three hemothorax all requiring re-intervention. Minor complication rate was 25.5%. After a median survival of 37 months (range, 1-144 months), 20 patients (45.4%) were alive. Five-year survival and disease-free interval were 39% and 45.8%, respectively. Patients with N0 and R0 disease had a best prognosis (log-rank test: p=.03, and p=.01, respectively). IT neither influenced survival nor postoperative complications. At multivariate analysis, pN0 [p=.04 (95% CI: 0,65-9,66)] and negative atrial margins [p=.02 (95% CI: 0,96-8,35) were positive independent prognostic factors.
Conclusion
Resection of T4atrium is technically feasible without mortality and acceptable morbidity. Patients with N2 cancers should not be operated on. Lung cancer invading left atrium should not be systematically considered as a definitive contraindication to surgery.
-
+
EP1.01-44 - Early and Long-Term Results of Tracheal Sleeve Pneumonectomy for Lung Cancer After Induction Therapy (Now Available) (ID 2794)
08:00 - 18:00 | Presenting Author(s): Domenico Galetta
- Abstract
Background
The role of induction therapy (IT) and its effects on morbidity and mortality of patients receiving tracheal sleeve pneumonectomy (TSP) are unclear. We evaluated early and long-term outcomes of patients who underwent TSP after IT.
Method
From 1998 to 2018, 32 patients (26 men; median age, 63 years) underwent TSP. Twenty-two patients (69%) received IT (cisplatin-based chemotherapy). The TSPs were all right sided and included three completion pneumonectomies. Superior vena cava resection was combined with TSP in 15 cases. Diaphragmatic and vertebral resection was also associated in 1 case each.
Result
Operative mortality was nil. Thirty-day mortality was 9% (n = 3). Major complications occurred in 7 patients (21.8%): bronchopleural fistulas in 3; acute respiratory distress syndrome in 2; cardiac hernia in 1; and empyema in 1. The IT had no significant effects on morbidity and mortality. Resection was complete in 31 patients (97%). Pathologic N status was N0 in 2 cases, N1 in 17, and N2 in 13. Nodal downstaging was diagnosed in 13 of 22 patients (59.1%) who received IT (11 passed from N2 to N1, and 2 to N0). Mean survival was 36 months (range, 1 to 181). Overall 5-year survival and disease-free survival were 30.3% and 27.7%, respectively. Patients receiving IT had a poor survival (p = 0.03). At multivariate analysis, nodal downstaging and adjuvant treatment significantly affected survival (p = 0.035 and p = 0.007, respectively).
Conclusion
Tracheal sleeve pneumonectomy is a feasible but technically challenging surgical procedure and provides acceptable results in terms of early and long-term outcomes. Induction therapy did not significantly affect morbidity and mortality.
-
+
EP1.01-56 - Co-Presentation of Adenocarcinoma and Squamous Cell Lung Carcinoma Harbouring ALK Rearrangement in Different Sites (Now Available) (ID 1416)
08:00 - 18:00 | Presenting Author(s): Domenico Galetta
- Abstract
Background
Approximately 4% to 9 % of NonSmallCellLungCarcinoma (NSCLC) contain mixed adenomatous on squamous pathologies (adenosquamous cell carcinoma). The lung ADC to SCC transdifferentiation as a drug-resistance mechanism has been recently described. While the histological transformation mainly described in ALK-positive patients is from NSCLC entity to SCLC, only one case of histologic transformation of ALK rearranged ADC to SCC after treatment with an ALK inhibitor has been reported. Importantly, transformed samples retain the initial genomic alteration, supporting the lineage transition as a novel resistance mechanism.We describe an unique case of co-presentation of ADC and SCC in two different disease sites, both harbouring ALK rearrangement.
Method
A 57-year-old male never smoker presented with a left adrenal mass. CT Scan showed a right superior lobe mass, bilateral pulmonary nodules (Fig. 1 A), and bone metastases. The lung biopsy documented ADC with moderate differentiation and ALK rearrangement by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC).
Result
The patient was treated with Crizotinib but, after 4 months, the CT showed a near complete response of the pulmonary disease (Fig. 1 B), while a progression of the left adrenal metastasis was observed. (Fig. 2 A, Fig. 2B). A left adrenal biopsy showed a SCC histology, with ALK rearrangement confirmed both by IHC and FISH. The treatment was switched to alectinib without respoinse so the patient received chemotherapy.
Conclusion
The absence of an initial biopsy of the adrenal mass doesn't allow to distinguish between a lung ADC to SCC transdifferentiation with a consequence of the treatment-induced selection pressure, so a preexisting SCC at the time of diagnosis would exhibit tumor dominance after elimination of the ADC. However, the presence of the ALK rearrangement in the adrenal biopsy suggest a possible ADC to SCC transdifferentiation in the early phase of metastases development as a new potential mechanism of drug resistance
-
+
EP1.01-81 - Resection of Tumors with Carinal Involvement After Induction Therapy (Now Available) (ID 2790)
08:00 - 18:00 | Presenting Author(s): Domenico Galetta
- Abstract
Background
Tumors involving the carina may be treated with resection of trachea-bronchial bifurcation with or without lung resection. The role of induction therapy (IT) and its effects on morbidity/mortality are unclear. We evaluated surgical and long-term outcomes of patients who underwent carinal resection after IT.
Method
From 1998 to 2018, 45 patients (35 men; median age, 62 years) underwent carinal resection. Twenty-nine patients (64.4%) received IT (24 chemotherapy and 5 chemo-radiation). Histology included 41 non-small cell lung cancers, 3 adenoid cystic carcinomas, 1 carcinoid. Carinal pneumonectomy was performed in 32 cases (all right sided), carinal resection plus right upper lobectomy in 9, carinal resection plus upper bilobectomy in 1, and carinal resection without pulmonary resection in 3. Superior vena cava resection was associated in 22 cases.
Result
Operative mortality was nil. Thirty-day mortality was 8.8% (n=4). Major complications occurred in 9 patients (20%): 5 bronchopleural fistulas, 2 ARDS, 2 cardiac hernias. IT did not influence morbidity rate (p=.7371). Pathological N status included 6 N0, 22 N1, and 17 N2. Follow-up was completed for all patients. Median survival was 16 months (range, 1 to 181 months). Overall 5-year survival rates was 35.8%. Overall, 5-year freedom from recurrence was 49.8%. Patients receiving IT had a poor survival (22.6% versus 60%) but it was not statistically significant (p=.0596). Histology, extended resection, and N status, did not influence survival.
Conclusion
Carinal resection is a feasible but challenging procedure providing acceptable mortality and long-term outcomes. IT did not influence morbidity, mortality, and overall survival.
-
+
EP1.04 - Immuno-oncology (ID 194)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
-
+
EP1.04-38 - A Case of Lichenoid Reaction as Late and Uncommon Immune-Related Skin Toxicity During Nivolumab Treatment (Now Available) (ID 1408)
08:00 - 18:00 | Author(s): Domenico Galetta
- Abstract
Background
Immune-checkpoint inhibitors have shown remarkable activity in advanced Non-small cell lung cancer (NSCLC).
An increasing number of immune-related skin toxicities has been reported , also heterogeneous and unusual. So, these reports could be useful to manage such events.
Lichenoid dermatitis (LD) identifies a group of dermatoses clinically and histologically reminiscent of idiopathic lichen planus (LP). Pharmacologycal, chemical and viral causes agents can induce skin lichenoid reactions.
Method
Result
We report the case of a 81-years-old man with stage IV non-small cell lung cancer treated with Nivolumab developing a hitchy, recurrent and polymorphous lichenoid eruption after 36 cycles of treatment (Figure 1).
A skin biopsy (Figure 2) showed an area of parakeratosis associated to a dense lympho-histiocytic infiltrate of the papillary derma that obscures the basal membrane and causes vacuolization of the basal layer of the epidermidis with an isolated Civattes body (red arrow), (40
X, H&E).The temporary interruption of Nivolumab , together with short and low-dose cycles of corticosteroids repeated for several times due to the wave evolution of the lichenoid reaction, allowed for the partial recovery of the skin toxicity and the resumption of treatment.
Conclusion
Unlike the classic appearance of lichenoid reactions, this patient showed a more polymorphous lesions as compared to the classic forms .
The correct and early recognition of these uncommon effects is useful to optimally manage and safely continue a treatment while achieving a therapeutical response of neoplastic disease
-
+
EP1.17 - Treatment of Early Stage/Localized Disease (ID 207)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
-
+
EP1.17-19 - Robotic-Assisted Thoracic Surgery for Early Stage Lung Cancer: Ten Years' Single Institution Experience (Now Available) (ID 2770)
08:00 - 18:00 | Presenting Author(s): Domenico Galetta
- Abstract
Background
Less invasive surgical resection for early stage lung cancer is gaining popularity. We analyzed the short- and long-term outcomes of robotic-assisted thoracic surgery (RATS) for early stage non-small cell lung cancer (NSCLC).
Method
We retrospectively reviewed 339 patients who underwent RATS for clinical stages I (n = 318) or II (n = 21) NSCLC from November 2006 to December 2016 and we analyzed long-term survival by Kaplan-Meier method.
Result
Twenty-nine patients underwent segmentectomy, 307 lobectomy, and 3 pneumonectomy. Conversion occurred in 22 patients (6.5%): 15 (4.4%) due to technical issues, 4 (1.2%) for oncological reasons, and 3 (0.9%) for bleeding. The median number of N1 and N2 stations resected was 2 and 3, respectively, and the median number of N1 and N2 lymph nodes resected was 9 and 6, respectively. Median operative time was 192 minutes for lobectomy, 172 minutes for segmentectomy, and 275 minutes for pneumonectomy. Median length of hospital stay was 5 days (2-191). The most common postoperative complication was prolonged air leak (12.1%). Major complications occurred in eight patients (2.4%). The 30-day and 90-day operative mortality was 0% and 0.3%, respectively. Two and 5-year cancer-specific survival rate was 96.1% and 91.5%, respectively. Five-year survival rate was 96.2% for patients who underwent segmentectomy, and 89.1% for lobectomy. All three patients who underwent pneumonectomy were alive at 5 years with no disease.
Conclusion
Besides the well-known short-term outcomes showing very low morbidity and mortality rates, mediastinal lymph node dissection during RATS adequately assesses lymph node stations detecting occult lymph node metastasis and leading to excellent oncologic results. However, these results await longer follow-up studies.
-
+
MA10 - Emerging Technologies for Lung Cancer Detection (ID 129)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Screening and Early Detection
- Presentations: 1
- Now Available
- Moderators:Fabrizio Bianchi, Marcelo Sanchez
- Coordinates: 9/08/2019, 15:15 - 16:45, Dublin (1997)
-
+
MA10.05 - Breath Analysis: New Key-Challenges for Early Detection of Lung and Pleural Neoplasms (Now Available) (ID 959)
15:15 - 16:45 | Author(s): Domenico Galetta
- Abstract
- Presentation
Background
The growing interest about breath analysis relies on the need of tools to get an early diagnosis of respiratory pathologies with high mortality rate such as lung cancer (LC) and malignant pleural mesothelioma (MPM). Nowadays the key-challenge of the scientific community is the search for non-invasive diagnostic biomarkers able to identify patients at risk of developing cancer or with early stage cancer. A diagnostic progress would be crucial to improve the survival outcome of these neoplasms, generally detected at an advanced stage. The analysis of Volatile Organic Compounds (VOCs) pattern in human breath for early detection and follow-up of diseases such as cancer is low-cost, non-invasive and promising alternative to traditional exams (i.e., colonoscopy, biopsy).
Method
This study is based on the development and validation of a methodological approach aimed to the identification of VOCs breath pattern to discriminate between patients affected by both LC and MPM, and healthy controls (CTRL). A total of 80 breath samples from 36 patients with LC, 14 patients with MPM and 30 CTRL have been collected into inert Tedlar bags, transferred to sorbent tubes (biomonitoring, Markes) and analysed by TD-GC/MS (TD Markes Unity 2 - GC Agilent 7890/MS Agilent 5975).
Result
Non parametric test as Wilcoxon/Kruskal Wallis tests (R version 3.5.1) allowed to identify the most weighting variables in discrimination between LC, MPM and HC breath samples. On the basis of p-values lower than 0.05 (selection between CTRL and LC, and between CTRL and MPM) and current knowledge on metabolic processes, a multivariate statistics (Principal Components Analyses (PCA) -PAST 3.20) has been applied on breath samples, considering only selected variables. The preliminary statistical elaboration by PCA of data collected from the analysis of LC and CTRL samples have shown two principal components: PC1 characterized by higher loadings of benzoic acid, methylcyclohexane and hexanal, and PC2 characterized by high loadings for dimethyldecane, pentane and pentanal. Similar results were obtained by PCA applied to MPM and CTRL breath samples considering 2-methylpentane, cyclopentane, hexane and 2-butanone as discriminant variables.
Conclusion
PCA was able to discriminate between LC and CTRL and between MPM and CTRL breath samples. Leave-one-out cross-validation method was applied to calculate the prediction accuracy obtaining good sensitivity (88%), accuracy (86%) and specificity (92%).
Further investigation about breath analysis is strongly warranted, due to the need of biomarkers potentially useful both for the screening of high-risk subjects and for the early diagnosis of lung and pleural neoplasms.
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.
-
+
P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
-
+
P1.01-59 - Expanding Access to Large-Scale Genomic Mutational Analyses for Patients with Advanced NSCLC in Italy (ID 2410)
09:45 - 18:00 | Author(s): Domenico Galetta
- Abstract
Background
In NSCLC, large-scale mutational analysis facilitates access to targeted treatments but is still not routinely employed due to significant technological barriers. The Alleanza Contro il Cancro (ACC) network of Italian Cancer Centers developed an affordable targeted sequencing panel for the identification of multiple genetic alterations with potential clinical utility, and designed a prospective multicentric trial to recruit 1000 newly diagnosed advanced NSCLC patients, aiming to i) compare panel performance against a set of externally validated biomarkers, including alterations in standard-of-care (EGFR, ROS1 and ALK) and non-standard-of-care (KRAS, BRAF, MET) biomarkers; ii) identify alterations in a large dataset of driver and potentially actionable genes; iii) correlate genotypes to survival outcomes and toxicity; iv) carry out ancillary studies on additional biomarkers and/or on specific patient groups (e.g. mutational burden, cfDNA, extensive characterization of immunotherapy-treated patients); v) build a centralized data repository for mutation interpretation and clinical recommendation.
Method
Through systematic literature mining and ad-hoc developed bioinformatic pipelines we identified: i) a set of 164 potentially actionable genes in solid tumors; ii) additional 18 genes with predicted driver function in NSCLC; iii) 70 actionable fusion transcripts; iii) 141 SNPs associated with pharmacogenomics markers. We designed a custom enrichment panel (~800 kb target) and compared PCR- and hybridization-based enrichment on semiconductor or by-synthesis sequencing to be subsequently deployed in a large observational trial. Sequencing is decentralized, to allow rapid turnaround time, but raw and processed data are collected in a single informatic infrastructure for centralized quality control and continuous bioinformatic pipeline improvement.
Result
PCR/semiconductor sequencing was selected for deployment based on cost and feasibility (2-day, highly automated workflow). 182 patients have been enrolled to date (90% stage IV, 10% IIIB). Of 65 patients with treatment information available, 28 (43%) subsequently received immunotherapy and 13 (20%) targeted therapy. For 56 patients with complete sequencing data, EGFR and KRAS status was concordant in 9/10 and 38/41 cases; discordant cases are being validated with orthogonal methods. Clinically significant MET amplifications were called in 2/2 cases. Remaining target regions did not show pathogenic alterations. Multiple alterations in potentially actionable genes were identified.
Conclusion
Large-scale sequencing is reliable, feasible and sustainable across multiple hospitals and provides clinically relevant results. The increased availability of genomic information may result in enhanced access to tailored therapies. Data and sample integration in centralized, shared repositories will allow multiple ancillary studies.
-
+
P1.04 - Immuno-oncology (ID 164)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
-
+
P1.04-58 - Uncovering the Tumor Microenvironment of KRAS-Driven Lung Adenocarcinoma: The Link Between Th17 Signaling and B Cell (ID 2393)
09:45 - 18:00 | Author(s): Domenico Galetta
- Abstract
Background
Non small cell lung cancer, been histologically classified into adenocarcinoma (AD) and squamous cell carcinoma, is one of the most deadly malignancy worldwide. Lung AD (LUAD) could benefit of a plethora of target therapies and, in the last few years, also of immunotherapies. Here we focused on a cohort of LUAD aiming to gain insights into the immune contexture of such a malignancy.
Method
20 patients affected by advanced LUAD, previously analyzed through the CE-IVD Oncomine solid tumor DNA kit, have been included in our cohort. DNA and RNA were isolated from 6 μm thick FFPE sections usingthe QIAamp DNA/RNA FFPE Tissue Kit (Qiagen). Two custom panels were designed using Ion Ampliseq Designer Tool. DNA and RNA libraries were prepared according to manufacturer’s instructions. Torrent suite variant caller and Vardict tool were used to call variants, subsequently annotated with Annovar. RNA raw read counts were analyzed by DESeq2 R package. TIMER web-tool was used to deconvolve immune-cytotype composition and LUAD-TCGA dataset has been used to validate our findings. Immune infiltration results were validated with immunohistochemistry in an independent cohort.
Result
We explored the mutational status of 41 genes and the expression of 94 genes, related to immune-checkpoint, inflammation and stromal microenvironment. Surprisingly, we found that our cohort has a very low mutational burden if we consider our panel as its surrogate. Regarding gene expression data, we identified 31 genes significantly deregulated in tumor tissues compared with a pool of normal pleura samples. Unsupervised hierarchical clustering of the deregulated genes is able to identify two clusters of tumor samples, differently enriched in alterations in actionable. In particular, we identified a cluster enriched in patients carrying KRAS alterations. GO/KEGG enrichment displayed terms related, as expected, to T cell differentiation but more interestingly term linked to Th17 lymphocytes. Thus, we perform in silico deconvolution through TIMER algorithm. Estimation performed on our gene expression matrix showed that, after stratification based both on cluster and KRAS mutational status, B cell infiltration is lower in KRAS-mutated enriched cluster. Notably, also in LUAD-TCGA dataset, B cell infiltration is significantly low in KRAS mutated patients. Such a finding has been validated in situ through immunohistochemistry in an independent cohort. Moreover, cases in LUAD-TCGA with low B cell infiltration have a significantly worse overall survival than those with higher levels. In our cohort we observed that cases belonging to cluster enriched in KRAS-mutated patients have a poor outcome.
Conclusion
LUAD driven by KRAS mutation represents an unmet clinical need, being refractory to pharmacological inhibition. Our results link KRAS mutations to composition and in particular to B cell infiltration. The role of B cell in tumor microenvironment of lung cancer has been previously explored, demonstrating that low level of infiltration is related to short survival. Interestingly, we found that deregulated genes are enriched in GO/KEGG terms related to Th17, which, through CXCL13 signaling, support B cell recruitment. Thus, the present findings could be helpful in a better definition of immunotherapeutic approaches for KRAS mutated patients.
-
+
P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 2
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
-
+
P1.14-03 - Molecular Determinants for Lorlatinib Activity in ROS1 Positive NSCLC: Results of the Prospective PFROST Trial (ID 1566)
09:45 - 18:00 | Author(s): Domenico Galetta
- Abstract
Background
Lorlatinib, an ALK/ROS1 inhibitor, demonstrated activity in ROS1+ NSCLC pretreated with crizotinib. However, molecular events predictive for tumor response during lorlatinib treatment are largely unknown.
Method
PFROST was a prospective phase II trial designed to include ROS1+ NSCLC refractory to crizotinib. Eligible patients were treated with lorlatinib at the daily dose of 100 mg until disease progression. Primary end point was response rate (RR). For all included patients pre-lorlatinib tumor tissue or blood sample collection was mandatory. At the time of lorlatinib failure liquid biopsy was recommended. The samples were then run with the NEOliquid assay, specifically designed for liquid biopsies, or NEOselect, a panel optimized for formalin-fixed paraffin-embedded (FFPE) tumor tissue, covering 39 cancer related genes.
Result
From June 2017 to April 2019, 22 ROS1+ crizotinib refractory lung adenocarcinoma patients were included in 10 Institutions. Median age was 56 years (range 39-82); male/female: 8/14; ECOG PS 0 (N=8; 36.4%), PS1 (N=14; 63,6%); The majority had brain metastases at baseline (N=15; 68.1%), were never smokers (N=13; 59.1%) and received lorlatinib as third line therapy (N=16; 72.7%). In all cases crizotinib was the last therapy line before lorlatinib. At the time of the present analysis, trial completed its accrual and 13 patients are still receiving therapy. A total of 18 patients were evaluable for response and 7 had confirmed complete (N=1) or partial (N=6) responses for an overall RR of 38.8%. In 4 patients, response to therapy was not yet evaluated. A total of 10 tissue biopsies and 20 blood samples obtained after crizotinib and before lorlatinib therapy were collected. For 7 samples analyses are ongoing. Among responders, no patient harbored a secondary ROS1 mutation. Conversely, no response was observed among patients with secondary ROS1 mutations (N= 1 ROS1S1861I, N=1 ROS1 V2054A, N=3 ROS1G2032R). All patients harboring the ROS1G2032R mutation rapidly progressed and maintained this aberration in liquid biopsy at the time of radiological evidence of lorlatinib failure.
Conclusion
In our study lorlatinib confirmed its efficacy in crizotinib resistant ROS1+ NSCLC. Molecular profile of refractory patients suggests reduced efficacy in individuals developing secondary ROS1 mutations after crizotinib failure.
-
+
P1.14-26 - ALK Fusion Variant Detection by Targeted RNA-Seq in TKIs Treated ALK-Positive Lung Adenocarcinoma (ID 1860)
09:45 - 18:00 | Author(s): Domenico Galetta
- Abstract
Background
Clinical outcomes of ALK positive (ALK+) Non-Small-Cell Lung Cancer (NSCLC) and the identification of the most effective anaplastic lymphoma kinase inhibitor (ALKi) according to the specific ALK fusion variants are not well assessed. We retrospectively characterized fusion variant distribution in a cohort of ALK+ lung adenocarcinomas (ADC) with paired clinical data about treatments and outcomes.
Method
Diagnostic tumor tissue from advanced ALK+ (by FISH and/or IHC) ADC diagnosed from 2010 to 2018 and treated with single or multiple ALKis were collected (expanded cohort from Gobbini et al. Lung Cancer, 2017). The OncomineTM Solid Tumor Fusion Transcript Kit on an Ion PGM™ system and the Ion Reporter™ software were used to identify targeted ALK fusion gene products (ThermoFisher).
Result
Specific fusion variant transcripts were found in 34/55 (62%) of collected samples. As expected, EML4-ALK fusion transcripts were the most common (31/34 samples, 91%), but HIP-ALK transcripts were also detected (3/34 - 9%). Among EML4-ALK fusions the following variants were detected: V1 (n=11); V2 (n=2); V3a/b (n=12 ) V5a/b (n=5 ) and E6A19 (n=1). Patient median age was 60 year [range 36-85], 22 were male and 12 female. Three patients were current, 11 former and 20 never smokers. Crizotinib, alectinib, ceritinib, brigatinib and lorlatinib were the ALKis used. Independently of the therapy line, 12 patients received crizotinib only, while 22 patients received crizotinib followed by one or two other ALKis. Regardless of the type of transcript, those patients who received more than one ALKi had a better median overall survival compared to those receiving crizotinib only, as expected (74 vs 21 months, HR: 5.31; 95%CI: 1.464-19.26, log rank p=0.0006). Furthermore, a significant difference in the mean duration of the different ALKi treatment was found according to the ALK variants (Chi-square p<0.0001), suggesting a private ALKi efficacy profile for specific fusion variants. Finally, the 3 HIP-ALK cases showed a better outcome with respect the EML4-ALK variants (not reached vs 51 months).
Conclusion
Our analysis suggests that different ALK fusion variant might affect ALKi treatment duration in ALK+ lung ADC.
-
+
P1.15 - Thymoma/Other Thoracic Malignancies (ID 184)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Thymoma/Other Thoracic Malignancies
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
-
+
P1.15-01 - Prognostic Factors and Long-Term Outcomes After Pulmonary Metastasectomy from Renal Cell Carcinoma (Now Available) (ID 2816)
09:45 - 18:00 | Presenting Author(s): Domenico Galetta
- Abstract
Background
Treatment of pulmonary metastases from renal cell carcinoma (RCC) remains controversial. However, some studies revealed potential survival benefits of pulmonary metastasectomy (PM) in these patients. We evaluate our experience analyzing surgical results, postoperative outcomes, and prognostic factors in patients receiving PM for RCC.
Method
Using a prospective database, we retrospectively reviewed data from 133 patients who underwent PM for RCC between 1998 and 2018. There were 93 men (median age, 62 years, range, 29-80). Surgery included 104 wedge/segmentectomies (78.2%), 28 lobectomy/bilobectomy (21.0%), one pneumonectomy (0.8%). Twenty-one patients (15.8%) received a redo-metastasectomy. A single metastasis or 2-3 metastases were removed in 42 patients (31.6%) each; in 91 patients (68.4%) 4 or more metastases were removed. Lymphadenectomy was performed in 84 patients (63.2%): 58/84 (69.1%) were pN0, and 26/84 (30.9%) were pN+.
Result
Complete resection was achieved in 124 patients (93.2%). Mortality was nil. We had only minor complications occurring in 23 patients (18.0%). After a median follow-up of 2.5 years (range, 0.03-13.3 years), 102 patients (76.7%) were alive. Five and 10-year survival were 57% and 53%, respectively. Disease-free interval was <12 months in 39 patients (29.4%); between 12 and 36 months in 33 (24.8%), and >36 month in 61 (45.8%), respectively. DFI and complete resection did not influence survival rate. Number of resected metastases influenced long-term outcome (60% for less 3 metastases versus 32% for 4 or more, log-rank test: p=.02). Patients with nodal involvement had a poor survival (58% for N0 versus 29% for N+, p=.01). At multivariate analysis, both number of resected metastases and nodal involvement were independent prognostic factors [p=.03 (95% CI: 0,66-8,46) and p=.001 (CI: 0,57-6,35), respectively].
Conclusion
PM may be a promising treatment for metastatic RCC allowing a good long-term survival rate. Nodal involvement and a number of resected metastases equal or more than 4 are predictors of poor survival.
-
+
P1.15-11 - Intrathoracic Neurogenic Tumors: Clinical, Pathological, and Long-Term Outcomes (Now Available) (ID 2823)
09:45 - 18:00 | Presenting Author(s): Domenico Galetta
- Abstract
Background
Intrathoracic neurogenic tumors are uncommon neoplasms arising from nerve tissues. We report our single-center experience in treating this rare intrathoracic neurogenic tumors.
Method
We retrospectively analyzed the clinical, surgical and pathological records of patients receiving the resection of an intrathoracic neurogenic tumor between May 1998 and December 2018.
Result
There were 82 patients (24 females) with an average age of 53 years (29 to 75 years). Mean diameter was 32 mm, ranging from 12 mm to 68 mm. Histology included 42 benign schwannomas, 7 malignant schwannomas, 15 neurinomas, 14 neurilemmomas, and 4 paragangliomas. 55 were located in the posterior mediastinum, 13 in the thoracic inlet, 7 in the anterior mediastinum, 4 in the lung parenchyma, and 3 in the chest wall. Symptoms were seen in 51 patients (62.2%) and including cough in 23, dyspnea in 15, neurologic symptoms in 11, and wheezing in 2. In 3 patients (3.6%), the tumor showed an intraspinal extension. Tumor resection was made by thoracotomy in 42 (51.2%) cases and thoracoscopy in 40 (48.8%). Resection was complete in 80 patients (97.6%). Postoperative radiotherapy was administerd in 2 cases. Mortality was nil. Morbidity rate occurred in 4 patients (4.8%) and included 2 prolonged air leaks, 1 hemothorax, and 1 chylothorax. Five-year survival was 97% in an average follow-up of 4.9 years. No recurrence occurred during the follow-up period neither for malignant nor for benign tumors.
Conclusion
The treatment of choice for thoracic neurogenic tumors is complete resection. Long-term prognosis is favorable both for malignant and benign neurogenic tumors.
-
+
P1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 186)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
-
+
P1.16-09 - Post-Progression Outcomes After Pembrolizumab in Patients with NSCLC and High PD-L1 Expression: Real-World Data from a European Cohort (ID 2749)
09:45 - 18:00 | Author(s): Domenico Galetta
- Abstract
Background
Real-world data regarding treatment patterns and clinical outcomes after progression on first-line pembrolizumab (pembro) monotherapy among NSCLC patients are lacking.
Method
A comprehensive clinicopathological database of 173 consecutive patients with NSCLC and PD-L1>50% treated with first-line pembro in 14 centers in Italy, Spain, Greece and Switzerland was retrospectively created and post-progression patterns and outcomes were recorded. Analysis was performed using the SAS 9.3 software.
Result
Main clinicopathological features are summarized in Table 1. Median TPS score for PD-L1 expression was 70%. Median duration of pembro treatment was 6.1 months (range: 0.2-20.8). Thirty patients (17.4%) received pembro despite having non-metastatic disease (stage I-IIIC), as deemed medically inoperable or ineligible for definite chemo-radiotherapy. At data cut-off (10th April 2019), 100 patients (58%) had stopped treatment due to disease progression, 9 (5%) due to toxicity, 3 (2%) for other reasons and 61 (35%) were still on treatment. Best response to pembro was CR, PR, SD and PD in 2%, 34%, 20% and 24% respectively, while in 11.6% death occurred in the absence of documented PD. Among patients who progressed (N=100), in 18 cases pembro was continued beyond progression, as considered to confer clinical benefit. Among patients who discontinued pembro (N=94), 47% received any second-line chemotherapy and 53% received no further treatment. Main chemotherapy regimens were carboplatin with either pemetrexed (16%) or gemcitabine (9%) or paclitaxel (7%), cisplatin-pemetrexed (7%) and gemcitabine monotherapy (9%). Best response to chemotherapy was CR, PR, SD and PD in 2%, 30%, 11% and 32% respectively. After a median follow-up of 11.2 months, median OS was 13.5 months (range: 0.16-25.8+).
Table 1: Main clinicopathological characteristics of the patient cohort.
N=173
%
COUNTRY OF ORIGIN
Italy
98
56.7
Greece
32
18.5
Switzerland
27
15.6
Spain
16
9.2
SEX
Male
112
64.7
Female
61
35.3
AGE Median (Range) yrs
68 (19-86)
SMOKING STATUS
Current
66
38.2
Former
86
49.7
Never
18
10.4
Unknown
3
1,7
PERFORMANCE STATUS
0
50
28.9
1
80
46.2
2
41
23.7
3
2
1.2
HISTOLOGY
Adeno
116
67.1
Squamous
37
21.4
Large Cell
2
1.2
Pleiomorphic
3
1.7
Sarcomatoid
7
4.0
Poorly differentiated/
Undifferentiated
8
4.6
SITE OF METASTASIS
Bone
74
49.7
Intrapulmonary/Contralateral Lung
72
48.3
Adrenal
43
28.9
Brain
30
20.1
Liver
23
15.4
Other
63
36.4
TNM STAGE AT DIAGNOSIS (AJCCC v.8)
I
2
1.2
II
2
1.2
III
26
15.0
IV
142
82.1
Unknown
1
0.5
STEROID USE
Yes
48
27.7
No
105
60.7
Unknown
20
11.6
Conclusion
Real-world data in a large retrospective cohort, indirectly compared to Keynote 024, suggest that: 1) Due to it’s favorable toxicity profile, pembro is also an option in earlier stages in frail (PS=2 or medically inoperable stage I-III) patients, 2) One in five patients continues pembro beyond progression due to clinical benefit and 3) More than half of patients who progress do not receive any second-line treatment, mainly due to clinical deterioration.
-
+
P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
-
+
P2.01-15 - Phase II Single Arm Study of CABozantinib in Non-Small Cell Lung Cancer Patients with MET Deregulation (CABinMET) (ID 2637)
10:15 - 18:15 | Author(s): Domenico Galetta
- Abstract
Background
Mesenchymal-Epithelial Transition gene (MET) amplification and exon 14 skipping mutations are established oncogenic drivers in non-small cell lung cancer (NSCLC), both occurring in about 4% of cases. In patients with MET amplified or mutated lung cancer, oral MET tyrosine kinase inhibitors (TKI) showed promising activity. The American Food and Drug Administration has recently granted crizotinib a breakthrough therapy designation for MET exon 14 mutation positive NSCLC. Cabozantinib is a novel oral inhibitor of MET and other receptor tyrosine kinases that has shown preliminary activity in MET deregulated NSCLC patients pretreated with crizotinib, although definitive data on its therapeutic role are still missing.
Method
CABinMET (NCT03911193) is a phase II, single arm, multicenter study assessing the efficacy of cabozantinib in subject with MET amplification or MET exon 14 skipping mutation pretreated or not with MET inhibitors. The primary endpoint of the trial is overall response rate. Secondary efficacy endpoints are progression free survival, overall survival and disease control rate. Main inclusion criteria include histologically/cytologically confirmed diagnosis of advanced stage NSCLC, presence of MET exon 14 skipping mutation or MET amplification (MET/CEP7 ratio ≥2.2 on FISH analysis) on archival formalin-fixed paraffin-embedded (FFPE) tumor tissue or circulating tumor DNA, measurable disease, ECOG PS 0-1, at least 1 prior line of standard therapy, adequate organ function. Patients with co-existent driver events or with symptomatic brain metastases are excluded from the trial. Cabozantinib is administered orally at 60 mg once daily until disease progression, patient refusal or unacceptable toxicity. Disease is assessed every 8 weeks. Exploratory biomarker analyses are conducted on archival FFPE tumor tissue and on blood samples collected at baseline, at the time of the first disease assessment and at progression.
Result
The study is currently running in 9 Italian centers. Recruitment started in September 2018 and 6 of the planned 25 patients have been enrolled.
Conclusion
Enrollment will be completed in 24 months.
-
+
P2.01-74 - Clinical-Pathological Features and Outcome of Patients with Oral Metastases from Lung Cancer: A Multicenter Retrospective Study (ID 2701)
10:15 - 18:15 | Author(s): Domenico Galetta
- Abstract
Background
Oral metastases are a rare event, accounting to less than 1% of all oral malignancies, sometimes being the first manifestation of a wide-spread disease. Regardless of the site of the primary tumor, patients with oral metastases have a poor prognosis, with a reported median overall survival (mOS) of 6 months. Lung cancer, particularly small cell lung cancer (SCLC) and poorly differentiated carcinoma, represents the main source of oral metastases, even if large datasets still lack. We conducted a multicenter retrospective study investigating incidence, clinical-pathological features and outcome of patients with oral metastases from lung cancer.
Method
Between January 2014 and December 2018 we collected data from all consecutive patients diagnosed with lung cancer in four oncological Italian centers. Clinical-pathological features of those patients with oral metastases involving jaw or/and soft tissues were described.
Result
Among 4,082 consecutive lung cancer patients, the incidence of oral cavity metastases was 0.15% (6 out of 4,082 patients,). Patients were more frequently male (5 out of 6, 83%), current or former smokers (5 out of 6, 83%), with a median age at diagnosis of 61 years (range 53-69) [table 1]. Four different histotypes of lung cancer were detected. Five patients (83%) were stage IV ab initio, with synchronous histologically confirmed oral metastases. All these patients had distant metastases other than in the oral cavity (median of 5 different metastatic sites). The mOS since the diagnosis of oral metastases was 67 days (range 36-166).
Table 1. Patient characteristics
Gender
Age (years)
Smoke
Histotype
N° metastatic sites
Site of oral lesion
Time between stage IV diagnosis and oral lesion occurrence
Local radiotherapy
Median OS from oral lesion occurrence (days)
M
69
Current
Poorly differentiated
4
Jaw
Syncronous
Yes
57
M
61
Current
Sarcomatoid
5
Jaw
Syncronous
Yes
107
M
61
Former
Adenocarcinoma
3
Gum
11 months
Yes
77
M
53
Former
Poorly differentiated
4
Gum
Syncronous
No
44
M
59
Current
SCLC
5
Gum
Syncronous
No
36
F
66
Unknown
Squamous (mut ex 19 EGFR)
5
Gum
Syncronous
No
166
Conclusion
To our knowledge, this is the largest study assessing the incidence of oral metastases in lung cancer patients. Oral involvement, usually diagnosed at an advanced stage, seems to be associated with a very poor prognosis, with a mOS of about 2 months. Further confirmatory datasets are warranted.
-
+
P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
-
+
P2.04-07 - Surgical Resection of Advanced Lung Cancer After a Response to EGFR-TKI and/or Immunotherapy: A Single Institution Experience (Now Available) (ID 2801)
10:15 - 18:15 | Presenting Author(s): Domenico Galetta
- Abstract
Background
The usefulness of residual tumor resection after epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) or immunotherapy treatment remains unclear. We describe a single institutional case-series of patients who underwent residual tumor resection after responding to EGFR-TKIs and/or immunotherapy for advanced non-small cell lung cancer (NSCLC)
Method
Using a prospective database, we reviewed clinical, surgical, pathological, and prognostic data of 15 patients who underwent surgical resection of advanced lung cancer after a response to EGFR-TKI and/or immunotherapy between January 2016 and March 2019.
Result
There were 10 males and 5 females, all smokers; median age of 58 years (range, 43-72). All patients had T4N2 NSCLC. Five patients received only EGFR-TKI, 6 received EGFR-TKI and immunotherapy, and 4 only immunotherapy. Median time from beginning therapy to surgery was 17 months (range, 6-23 ). Surgery included 13 lobectomies, one right upper sleeve, and one right pneumonectomy. Lymph node dissection and vascular and bronchial isolation was extremely difficult. Intraoperative morbidity and mortality was nil. Postoperative morbidity was 20% (n=3) and included one bronchopleural fistula, one prolonged air leaks, one atrial fibrillation. Median hospital stay was 6 days (range, 5-15). Pathology showed 6 complete responses (40.0%) (2 after immunotherapy, 4 after EGFR-TKI and immunotherapy) and 9partial responses (60%). Moreover, the area of tumor clearance was characterized by (i) immune activation-dense tumor infiltrating lymphocytes; (ii) massive tumor cell death-cholesterol clefts; and (iii) tissue repair-neovascularization and proliferative fibrosis (each feature enriched in major pathologic responders versus nonresponders, p < 0.05). With a mean follow-up of 23 months, all patients are alive.
Conclusion
The timing and validity of a salvage surgery for residual lesions remain unclear when TKIs and/or immunotherapy are offered as first-line therapy to patients with advanced NSCLC. In our cases, surgery was performed with acceptable morbidity. Surgical resection of the residual tumor might contribute to good local control.
-
+
P2.04-14 - NLR, dNLR and PLR as Possible Predictive Markers in Patients with NSCLC Treated with ICI (ID 1063)
10:15 - 18:15 | Author(s): Domenico Galetta
- Abstract
Background
Clinical evidence suggests a possible predictive role of Neutrophil-to-Lymphocyte ratio (NLR), derived Neutrophils/(leukocytes minus neutrophils) ratio (dNLR) and Platelet-to-Lymphocyte ratio (PLR) in different tumors, including non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI).
Method
In this Italian multicenter retrospective trial NLR, dLNR, PRL fluctuations were analyzed in patients with stage IV NSCLC treated with ICI. Those rates were assessed at baseline, before the second, third and fifth cycles. In patients still on treatment, samples were collected also at 1 and at 2 years from ICI start. The primary objective was the relationship between baseline ratios and response to ICI, through the identification of different cut-offs estimated using ROC curves.
Result
Data of 402 patients receiving ICI (antiPD1 91%, antiPDL1 7% and antiPDL1 plus antiCTLA-4 2%) were analysed: 287 (71%) were males, median age was 65 (39-86 yrs-old), 84 patients (21%) were on first line treatment. The most common histology was adenocarcinoma (62%) and 95% of patients had an ECOG performance status of 0-1. One hundred and eleven (30%) patients were using steroids in permissive doses for ICI. Disease control rate (DCR) was observed in 228 patients (58%) with 95 (24%) reporting an immune objective response. Median progression free survival was 5,3 months and the median overall survival was 9,6 months, after a median follow-up of 9,6 months (range 4,0-13.0). Basal NLR, dNLR and PRL were predictive of response (p=0.0002, p=0.0003 and p=0.0304, respectively). Best response categories were dichotomized in Response (SD + PR + CR) versus no Response (PD). With this classification, the differences were more pronounced and statistically significant for basal NLR and dNLR (p=0,045 and p=0,004, respectively). The cut-off values for basal NLR and dNLR were defined (BLNLR=2,46; BLdNLR=1,61) to identify patients most at risk of “non Response” through the ROC curves. Confounding factors were assessed using logistic regression models (age, gender, smoking). During treatment, an increase in the values was observed at the time of progression, both for NLR (average variation: -1.57) and for dNLR (average variation + 0.32), even if the statistical significance is limited to NLR (p = 0.041).
Conclusion
NLR, dNLR and PLR are independent factors of response to ICI. Compared to the present literature data, this study highlights that NLR ratio may predict progressive disease earlier than radiological restaging.
-
+
P2.10 - Prevention and Tobacco Control (ID 176)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Prevention and Tobacco Control
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
-
+
P2.10-06 - Smoking Prevalence and Perceptions Among Healthcare Professionals: A Survey in an Italian Clinical Cancer Centre (Now Available) (ID 840)
10:15 - 18:15 | Author(s): Domenico Galetta
- Abstract
Background
A survey has been conducted on employees of our Clinical Cancer Centre about the smoking prevalence and knowledge of the smoking-related harms. The results have been compared to those emerged from a previous survey when the current smoke-free-hospital policies (national and internal) were not yet active.
Method
In June 2017, during two weeks, 400 subjects received an anonymous questionnaire (36items) investigating demographics, smoking-habits, secondhand-smoke exposure, knowledge of Italian smoke-free legislation.
Result
104 subjects (26%) returned the self-completed form (M=45.34years, SD=10.5; 67.3%women). 17,8%of responders were smokers, 26,2%former smokers, 56% no smokers, while in 23,8% the data were missing. Among the former smokers, the mean age of smoking cessation was 33,3 years (sd=10,2), without drugs in 77,3% of cases, for the following reasons: preventive health purposes (29,6%),a child birth (26%),suggestions from family members (3,%); no one stopped on medical advice. The ex-or never smokers share the working room with one (23,2%) or more (8,5%) smokers, pointing out the smoke exposure in hospital (30%), and feeling intense uneasiness (46,8%). The smoke-free-hospitals policy is not fully accepted, indeed only 40% declared that the smoking ban is observed and 63,2% said to smoke during the working-time.Regarding the policies that prohibit smoking inside and outside the hospital, the responders perceived it as a good way to protect the health (65,4%), to reduce the prevalence of smokers in hospital (20%), to protect non-smokers (46,1%) and to decrease tobacco-related disorders (37,5%) (p<0,001). The implementation of Italian smoke-free policies has favoured the reduction of the number of smoked cigarettes (55%), but did not increase the desire of a complete cessation (63%). A comparison of the surveys conducted in 2014 and 2017 is showed in Figure.
Conclusion
The adopted strategies are partially efficient; among personnel there is a large prevalence of smokers and interventions aimed at the development of a culture of health promotion are needed.
