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Dario Sanchez Cabrero
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EP1.06 - Mesothelioma (ID 196)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Mesothelioma
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.06-02 - Association of Inflammatory Biomarkers with Overall Survival in Patients with Advanced Malignant Pleural Mesothelioma (Now Available) (ID 1964)
08:00 - 18:00 | Author(s): Dario Sanchez Cabrero
- Abstract
Background
The inflammation process has been proposed as a mechanism of immunoresistance in patients with cancer, promoting cancer growth and dissemination. Derived neutrophil to lymphocyte ratio (dNLR) greater than 3 and lactate dehydrogenase (LDH) level greater than upper limit of normal (ULN) are associated with poor outcomes in patients with advanced non–small cell lung cancer. The aim of this study is to determine whether pretreatment levels of dNLR and LDH as well as PD-L1 status are associated with overall survival in patients with malignant pleural mesothelioma.
Method
We conducted a retrospective study, which included all patients with malignant pleural mesothelioma diagnosed in a tertiary referral hospital from December 2009 to March 2019. PDL1 status, complete blood cell counts and LDH levels were collected. A descriptive analysis was carried out, followed by a survival analysis using the Kaplan-Meier estimator.
Result
We selected 25 patients. No correlation was found between dNLR and LDH levels. 5 patients (20%) had a dNLR greater than 3, of which 3 patients had stable disease and 2 patients received supportive care. Patients with a dNLR greater than 3 had a median overall survival (mOS) of 8,5 months, whereas patients with a dNLR less than 3 had a mOS of 17,0 months, with statistically significant differences (P:0.038). 2 patients (8%) had a LDH level greater than ULN, of which 1 patient achieved a partial response and 1 patient had stable disease. Regarding the LDH level no difference in overall survival was found.
Regarding to the PD-L1 status, 10 (40%) of 25 patients had PD-L1 ≥ 1%, 8 (32%) had PD-L1 < 1% and 7 (28%) had unknown PD-L1. Patients with PD-L1 ≥ 1% had a mOS of 8,5 months, whereas patients with PD-L1 <1% had a mOS of 15,7 months, with no statistically significant association (P> 0.05).
Conclusion
In our sample, pretreatment levels of dNLR greater than 3 were correlated with worse overall survival in patients with malignant pleural mesothelioma. Furthermore, pretreatment levels of LDH greater than ULN and PD-L1 greater than or equal to 1% could be correlated with worse overall survival, although due to the size of our sample we are not able to conclude statistical significance. Further studies are needed to explore this relationship.
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EP1.06-11 - Advanced Malignant Pleural Mesothelioma: A Single Institution Experience (Now Available) (ID 1993)
08:00 - 18:00 | Author(s): Dario Sanchez Cabrero
- Abstract
Background
Malignant pleural mesothelioma is a rare and highly aggressive tumor that typically presents with advanced disease. The prognosis of patients with malignant pleural mesothelioma is poor and there is currently a lack of effective treatment options. The aim of this study is to analyze the experience of our center in the management of this pathology.
Method
We conducted a retrospective study, which included all patients with malignant pleural mesothelioma diagnosed in a tertiary referral hospital from December 2009 to March 2019. Data regarding baseline characteristics, treatment response and survival were collected. A descriptive analysis was carried out, followed by a survival analysis using the Kaplan-Meier estimator.
Result
We selected 25 patients. Table 1 summarizes the main sociodemographic characteristics, the histological subtype and the stage.
Table 1 Nº (%) Sex: Male/Female
19 (76%) / 6 (24%) Age (years):
71 (51 – 89)
Histology:
– Epithelioid mesothelioma
– Sarcomatoid mesothelioma
– Mixed mesothelioma22 (88%)
1 (4%)
2 (6%)Stage:
– Stage III
– Stage IV4 (16%)
21 (84%)22 (88%) of 25 patients received first line chemotherapy with platinum doublet with pemetrexed followed by pemetrexed maintenance and 3 (12%) received palliative care. The proportion of patients who received six cycles of platinum doublet with pemetrexed was 55%. 5 (20%) of 22 patients who received first line chemotherapy with platinum doublet with pemetrexed achieved a partial response, 15 (60%) had stable disease and 2 (8%) experienced disease progression.
After a median follow-up duration of 15,17 months, 19 (76%) patients had died. The median progression free survival was 13,1 months (IC 95%: 6,7 – 19,5), and the median overall survival was 15,7 months (IC 95%: 11,3 – 20,0). The major cause of death was cancer in 18 patients (95%) and 1 patient dead of heart disease.
Conclusion
Demographics and baseline characteristics as well as the survival data obtained in our sample are consistent with the previously reported. Further studies are needed to determine other treatment options to improve the prognosis of these patients.
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EP1.12 - Small Cell Lung Cancer/NET (ID 202)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Small Cell Lung Cancer/NET
- Presentations: 3
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.12-20 - Retrospective Study About the Impact of Metastatic Site in Small Cell Lung Cancer (Now Available) (ID 1980)
08:00 - 18:00 | Presenting Author(s): Dario Sanchez Cabrero
- Abstract
Background
Small cell lung cancer (SCLC) is a very aggressive type of lung cancer. It is characterized by a high cellular proliferation and an early development of widespread metastases (nearly 70% of patients presents macroscopic metastases at diagnosis). SCLC spread mainly to bone, brain and liver. In extensive disease, metastatic involvement of the liver, bone and central nervous system seems to have a worse prognosis comparing with other sites, though the studies are quite inconclusive.
Method
We conducted a descriptive and retrospective study including all patients diagnosed with metastatic SCLC between January 2012 and December 2018. A Kaplan Meier survival analysis (log-rank analysis) was carried out to study the impact of the metastatic involvement (depending on the localization) at diagnosis and at recurrence.
Result
Of the 58 patients included, 58.6% presents liver involvement at diagnosis. These patients present a worse overall survival (OS), with a mean of 1.9 months, and a clear trend to worse progression-free survival (PFS, with a mean of 5.6 months (P=0.56). Bone involvement was presented in 41.4% of the patients. No difference was observed neither in OS (with a median of 6 vs 7.9 months) nor PFS (3.9 vs 3.3 months). Lastly, only the 19% present brain metastases at diagnosis, and it didn’t show significant differences in OS (8.3 vs 6.7 months) but it did in SLP (2.6 vs 5 months). When the tumor relapses, it usually does in multiple localizations (51.3%) and the main organ involved is the lung (78.3%). It didn´t show any difference in prognostic between sites.
Conclusion
SCLC is a very aggressive tumor. Due to its biological behavior, a large proportion of the patients presents an advanced staged at diagnosis. In extensive disease, the number of organ sites involved is related to prognosis, but it´s not clear which localizations have a greater impact on survival rates. In our studies, liver and bone metastases are related to worse prognosis and short survival. Surprising, in our series, brain metastases don´t seem to impact in patient’s prognosis. When the tumor relapses, tumor extent (limited vs extensive) is a factor that affects the prognosis. However, in our experience, there are not clear differences between one or another, all of them related to poor prognosis. More studies will be needed to be able to clarify the prognostic impact of the metastases site, both at diagnosis and relapse.
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EP1.12-26 - Retrospective Study About the Impact of Brain Metastases and Cranial Irradiation in Small Cell Lung Cancer (Now Available) (ID 1987)
08:00 - 18:00 | Presenting Author(s): Dario Sanchez Cabrero
- Abstract
Background
Small cell lung cancer (SCLC) is a very aggressive type of lung cancer. Due to this behavior, it presents early development of metastases. Brain metastases (BM) are very common and are related with a great impact on both survival and quality of life. Prophylactic cranial irradiation (PCI) is used for patients without detectable brain metastases, improving survival and decreasing the incidence of brain relapses (BR). Cranial irradiation (CI) for affected patients are usually used in patients with clinical BM, but its benefits are less clear.
Method
We conducted a descriptive and retrospective study including all patients diagnosed with SCLC tumor between January 2012 and December 2018 (both localized and metastatic). We study the impact of PCI and CI in both patients with/without BM at diagnosis. A Kaplan Meier survival analysis (log-rank analysis) was carried out to study the overall survival and the impact of the radiotherapy treatment.
Result
Of the 98 patients included, 60.2% presents extensive-stage, while 39% were locally advanced. Of the advanced stages, only 18.4% presented brain involvement at the diagnosis. 34.7% of the patients received RT at the diagnosis (37.5% PCI and 50% of the patients with BM received CI).
Over the course of the disease, 35.1% of the patients present BR. 67.6% of the patients treated with RT at diagnosis (both PCI and CI) relapsed in the brain, meanwhile, the 54.8% in the group without RT (no significant differences). However, in the RT group, 69.5% of patients relapse outside the brain (mainly the lung). Chemosensitive didn´t show any relation with the incidence of BR (30.4% RT group vs. 35.7% in no-RT group). Overall, there were no significant differences in survival (p 0.19) between the group treated with RT (both PCI and CI) and the group which didn´t.
Conclusion
SCLC presents early dissemination. Brain is one of the main organs involved. PCI for patients without detectable BM decrease the incidence of brain relapses and improve survival. The impact of CI is less clear in patients that already have BM. Surprisingly, in our series, we didn´t find any difference with PCI or CI in overall survival and BR. A high proportion of the patients in both groups (with/without BM at diagnosis) didn´t receive radiotherapy, due to a very poor clinical status (which can may lead to bias). More studies will be needed to be able to clarify the prognostic impact of these metastases and the effectiveness of this treatment nowadays.
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EP1.12-29 - Retrospective Study About Small Cell Lung Cancer: Our Experience in a Spanish Hospital (Now Available) (ID 1976)
08:00 - 18:00 | Presenting Author(s): Dario Sanchez Cabrero
- Abstract
Background
Incidence of small cell lung cancer (SCLC) has been decreased during the last decades. This neoplasm appears almost exclusively in smokers and it is characterized by aggressive biology and early development of metastases. Due to this aggressiveness, a large proportion of patients present a poor performance status at the time of diagnosis. Though the tumor is initially highly responsive to therapies, most of the patients will relapse after treatment. The prognosis is generally poor, even in limited stage disease.
Method
We conducted a descriptive and retrospective study including all patients diagnosed with SCLC tumor between January 2012 and December 2018 (both localized and metastatic forms were included). A Kaplan Meier survival analysis (log-rank analysis) was carried out to study the overall survival.
Result
diagnosed in advanced stages (60.2%), while 29.6% were locally advanced and only 8.2%, localized. In metastatic stage, the main organ affected was the liver (35.7%), followed by the bone (24.5%). Only 12% presented brain metastases at the diagnosis. The vast majority were smokers (68.4%) or ex-smokers (27.6%), with only one patient that had never smoked.
The 78.4% of the patients received chemotherapy (36.7% with concomitant radiotherapy). After the initial treatment, up to 55.4% of the patients recurred, mainly involving various localizations (50%). Only 39% received a second line of chemotherapy, and 24% a third line.
At the end of the study, 84.6% of the patients had died (median of 19.7 months since diagnosis). Log-rank analysis (Kaplan-Meier estimates) showed significant differences (p<0.05) between tumor stages and platinum-sensitive status. On the contrary, there wasn´t significant difference related to sex, smoke status, type of recurrence or type of chemotherapy chosen in second line.
Conclusion
SCLC is heavily related with smoke. Most of them exhibit an aggressive behavior, with an advanced stage at diagnosis (in our study, up to 60.2%, and 29.6% locally advanced). Thought usually presents high chemosensitivity, most of the patients recur. At this point, the prognosis is poor, with a low benefit with the treatment, in our series regardless of the drug. Unlike the previous series, we haven´t seen a worse outcome related to sex or smoke status. More studies will be needed to be able to clarify the prognostic impact of factors such as the smoke status, sex, type of relapse or second line treatment.
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EP1.14 - Targeted Therapy (ID 204)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.14-31 - Retrospective Study About EGFR Mutations in Lung Cancer: Our Experience in a Spanish Hospital (Now Available) (ID 1995)
08:00 - 18:00 | Presenting Author(s): Dario Sanchez Cabrero
- Abstract
Background
Mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase are observed in approximately 15% of lung adenocarcinomas and usually occur in nonsmokers. The detection of these mutations can be detected either in liquid biopsies or solid tissue biopsies. EGFR mutations are a predictive biomarker for high response and longer survival (both progression-free and overall) with tyrosine kinase inhibitors (TKIs), namely gefitinib, erlotinib, afatinib and osimertinib.
Method
We conducted a descriptive and retrospective study including all patients diagnosed with EGFR mutations between January 2007 and September 2018 (both locally advanced and metastatic forms were included).
Result
Of the 67 patients, the mean age was 67.2 years. The majority were adenocarcinoma (82.5%), with only 7.9% of squamous and 6.4% large cell carcinoma. The main mutations registered were exon 21 deletion (41%) and exon 19 deletion (4.9%). Only 24.6% had history of smoking. 71.6% of patients present stage IV disease at diagnosis. The main organ involved was the bone (45.8%), followed by the lung (44.1%) and brain (25.4%). Also 13.6% presents pleural, 10.2% liver, 5.1% adrenal and 5.6% lymph node involvement.
84.1% of the patients were treated with TKIs (erlotinib 49.2%, gefitinib 16% and afatinib 19%) while 16% were treated with chemotherapy. With first line treatment, 94.7%presented disease control (41.8% partial response, 41.9% stable disease and 11% complete response). With a mean of 23.6 months, 56.9% of them progressed, mainly involving the lung (28.6%) and the bone (20.6%). Only 9.5% presented brain progression. At the end of the study, 34% had died (overall survival´s mean of 27.5 months).
Conclusion
In patients with oncogenic driver mutations in EGFR, treatment with TKIs results in a better outcome than standard chemotherapy. This mutation predicts sensitivity to EGFR (our study shows up to 94.7% presents some type of response). Also, this response is longer (23.6 months in our experience) and better tolerated than chemotherapy. Overall survival of these patients is longer too, in our series, round to 27.5 months of overall survival, and mainly related to the tumor stages. More studies will be needed to be able to clarify the prognostic impact of factors such as the smoke status, sex, type of relapse or second line treatment.
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EP1.18 - Treatment of Locoregional Disease - NSCLC (ID 208)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Treatment of Locoregional Disease - NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.18-28 - Neoadjuvant Therapy Among Patients Undergoing Resection for Non-Small-Cell Lung Cancer: A Single Institution Experience (Now Available) (ID 2002)
08:00 - 18:00 | Author(s): Dario Sanchez Cabrero
- Abstract
Background
Lung cancer is the leading cause of cancer deaths worldwide. Surgery alone results in poor overall survival in patients with stage III non-small cell lung cancer (NSCLC). Neoadjuvant therapy offers the ability to treat micrometastatic tumor cell dissemination preoperatively and increased resectability due to tumor regression. The aim of this study is to analyze the experience of our center and to identify clinical and pathological characteristics related to greater relapse-free survival (RFS).
Method
We conducted a retrospective study, which included all patients with NSCLC treated with neoadjuvant therapy follow by surgery in a tertiary referral hospital from April 2013 to March 2019. Data regarding clinical and pathological characteristics, treatment response, type of surgery and survival were collected.
Result
We selected 10 patients. Table 1 summarizes the main sociodemographic characteristics, the histological subtype, the stage, the regimens of neoadjuvant therapy and the types of surgery.
Table 1 Nº (%) Sex: Male/Female 6 (60%) / 4 (40%) Age (years): 62 (44 – 77) Performance status:
– 0
– 16 (60%)
4 (40%)Smoking:
– No
– Yes1 (10%)
9 (90%)Weight loss before diagnosis:
– High (≥5%)
– Low (<5%)1 (10%)
9 (90%)Histology:
– Squamous cell carcinoma
– Adenocarcinoma
– Large-cell cancer3 (30%)
6 (60%)
1 (10%)Stage:
– Stage IIIA
– Stage IIIB6 (60%)
4 (40%)Node status:
– N0
– N1
– N23 (30%)
1 (10%)
6 (60%)ALK translocation:
– No
– Yes
– Unknown8 (80%)
0 (0%)
2 (20%)EGFR mutation:
– No
– Yes
– Unknow8 (80%)
0 (0%)
2 (20%)Percentage of PD-L1 at diagnosis:
– < 1%
– 1 – 49%
– ≥ 50%
– Unknow5 (50%)
1 (10%)
2 (20%)
2 (20%)Neoadjuvant therapy regimens:
– Platinum – pemetrexed
– Platinum – vinorelbine
– Platinum – paclitaxel – bevicizumab
– Platinum – vinorelbine – gemcitabine
– Platinum – paclitaxel – nivolumab5 (50%)
1 (10%)
1 (10%)
1 (10%)
2 (20%)Types of surgery:
– Lobectomy
– Bilobectomy
– Pneumonectomy6 (60%)
1 (10%)
3 (30%)Percentage of PD-L1 after neoadjuvant therapy:
– < 1%
– 1 – 49%
– ≥ 50%
– Pathological complete remission
– Unknow2 (20%)
1 (10%)
4 (40%)
2 (20%)
1 (10%)Regarding tumour response rates after neoadjuvant chemotherapy, 2 (20%) of 10 patients achieved a complete response and 8 (80%) achieved a partial response. Furthermore, 5 (71%) of 7 patients with mediastinal lymph node involvement achieved a nodal downstaging. Using the Wilcoxon signed-rank test, there are statistically significant differences in the stage of the patients before and after the neoadjuvant chemotherapy (Z: -2,82, p:0,005).
After a median follow-up duration of 38 months, 5 (50%) patients had relapsed. The median RFS was 22 months (IC95%: 2–41). We did a multivariate logistic regression analysis, in which no statistically significant associations were found between clinical and pathological characteristics studied and the RFS (p>0,05).
Conclusion
Neoadjuvant therapy followed by surgery should be considered as standard treatment for a selective group of patients with stage III of NSCLC, in our sample all patients yielded excellent results. In the multivariate analysis no statistically significant associations were found due to the small size of our sample.
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P1.03 - Biology (ID 161)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Biology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.03-12 - Preclinical Validation of an Epigenetic Panel of Seven miRNAs at Early Stages NSCLC Patients and Its Prognostic Implications (Now Available) (ID 1385)
09:45 - 18:00 | Presenting Author(s): Dario Sanchez Cabrero
- Abstract
Background
Despite radical intent, many patients in early stages of NSCLC will recur. There is a need to find novel biomarkers able to help to identify patients in higher risk. Previous results from our group provide a miRNA signature from “in vitro” studies that might be involved in worst prognosis in NSCLC patients (PMID: 29158814). The main objective of this work is to analyse and compare the miRNA seven-panel signature in paired plasma (CIRmiARN) and tumor tissue samples (TmiARN) obtained from early stages NSCLC patients and to study the clinical implications.
Method
We conducted a descriptive study including 16 paired samples of patients diagnosed with early stage NSCLC. Both RNA from fresh tissue and plasma were extracted and the seven mRNAs levels were measured by qRTPCR(miR-7, -132, -335, -148, -10a, -124 and -9). Association between qualitative variables was analyzed using the chi-square test or Fisher's exact test. Mann-Whitney U test and the t-student test were used for qualitative and quantitative data comparison. A Kaplan Meier survival analysis (log-rank analysis) was carried out to study the overall survival and progression-free survival. Patients were also clustered in terms of tissue and plasma values, and then subgroups analyzed in terms of Survival. Difference between groups was analyzed with Cox Regression.
Result
There was no association between CIRmiARN and TmiARN expression levels and between clinical parameters. We found significant data associated with three miRNAs. There were significant differences (p<0.05) with low TmiR-132 expression level and worse survival and also a clear trend towards the group of patients with high levels of CIRmiR-7 and CIRmiR-124 and worst survival. Interestingly, we found an inverse correlation between CIRmiARN-132 and -124(p<0.05). Patients clustered regarding TmiR132 and CIRmiR-124 and -7levels, segregate in three clusters statistically significant in terms of survival (p<0.005), identifying a group of patients with a reduced risk of 78,6% (Hazard Ratio of 0.214 p<0,005).
Conclusion
Many patients diagnosed in early stages of NSCLC present a tumor relapse during the first 5 years. Genetic and epigenetic profiles help us to identify tumors with a greater risk of recurrence. In our study, we have identified three potential molecular candidates, both in liquid and tissue biopsies, which could have potential clinical use stratifying patients with higher risk of recurrence. Further studies will be needed to gain insight into the prognostic impact of these biomarkers in early and advanced stages NSCLC patients.
