Virtual Library

Start Your Search

Pamela Pizzutilo



Author of

  • +

    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
    • +

      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  |  Author(s): Pamela Pizzutilo

      • Abstract
      • Slides

      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).

      ct.jpgihc.png

      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

      Only Active 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 or select "Add to Cart" and proceed to checkout.

  • +

    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): Pamela Pizzutilo

      • Abstract
      • Slides

      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

      20190409_143719 (1).jpgWe 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).

      Result

      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), (40figure 2.jpgX, 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

      Only Active 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 or select "Add to Cart" and proceed to checkout.

  • +

    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
    • +

      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): Pamela Pizzutilo

      • Abstract
      • Presentation
      • Slides

      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.

      Only Active 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 or select "Add to Cart" and proceed to checkout.

  • +

    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): Pamela Pizzutilo

      • Abstract
      • Slides

      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.

      Only Active 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 or select "Add to Cart" and proceed to checkout.

  • +

    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
    • +

      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): Pamela Pizzutilo

      • Abstract
      • Slides

      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.

      Only Active 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 or select "Add to Cart" and proceed to checkout.

  • +

    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): Pamela Pizzutilo

      • Abstract
      • Slides

      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

      img_0301_1.jpg104 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.

      Only Active 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 or select "Add to Cart" and proceed to checkout.