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Joan Brunet
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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: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.12-15 - Oncologic Treatments and Outcomes for Small-Cell Lung Cancer Patients with Brain Metastases (Now Available) (ID 1877)
08:00 - 18:00 | Author(s): Joan Brunet
- Abstract
Background
Brain metastases (BM) are common in patients with small-cell lung cancer (SCLC), and are associated with short survival. Few data are available on this specific population of patients with SCLC and BM, as they are usually excluded from prospective randomized clinical trials.
Method
We present data on all patients diagnosed with BM from SCLC from the Cancer Register of the Hospital Universitari Dr. Josep Trueta during 2013–2017. Age, gender, and treatment in patients were recorded. Data cut-off for survival analysis was 28th March 2019.
Result
We identified 50 patients with SCLC and BM. Median age: 66 y (range: 48–82 y); male: 39 (78%). Synchronous BM were observed at the diagnosis of primary lung cancer in 33 (66%) patients. Impact of treatments on median overall survival (mOS) is summarized in Table 1. Only 1 patient received brain surgery (with an OS of 6.5 months). One-third of patients (34%) received best supportive treatment as unique treatment. The 1-year OS was 18% in our study.
Table 1 Treatment % mOS
(without treatment)mOS
(with treatment)p-value Brain radiotherapy 52 % 1.4 m 9.1 m < 0.000001 Chemotherapy 50 % 1.5 m 6.9 m =0.003 Brain radiotherapy and chemotherapy 34 % 1.6 m 10.7 m =0.000331
Conclusion
Our real-world data reinforce the need for better therapies to improve the prognosis of patients with SCLC and BM.
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-54 - Somatic Genome Alterations in Lung Cancer Patients Diagnosed with Li Fraumeni Syndrome (Now Available) (ID 1014)
09:45 - 18:00 | Author(s): Joan Brunet
- Abstract
Background
Li-Fraumeni syndrome (LFS) is a rare hereditary condition that consists of TP53 mutations inherited in autosomal dominant manner that confer high risk of developing cancer, including lung adenocarcinoma (LUAD). EGFR-mutated LUAD were reported in the context of LFS but there is no systematic description of somatic mutations and characteristics of lung cancer (LC) patients with LFS.
Method
We present a retrospective analysis of clinical and molecular characteristics of patients with LFS diagnosed with LC at the Catalan Institute of Oncology from 1999 to 2019. We collected demographical and clinicopathological features, germline and somatic mutational alterations, treatment and progression-free survival (PFS) and overall survival (OS).
Result
A total of 7 patients with LC and LFS were identified in the Genetic Counseling Unit database. They were carriers of germline mutations in TP53. Five of them were classified as pathogenic: c.638G>A; p.(Arg213Gln), c.725G>A; p.(Cys242Tyr), c.742C>T; p.(Arg248Trp), c.844C>T; p.(Arg282Trp) and c.1010G>A; p.(Arg337His) and two of them as likely pathogenic: c.374C>T; p.(Thr125Met) and c.473G>A; p.(Arg158His). Six out of 7 patients were female and 5 out of 7 never smoker. Median age at diagnosis was 38 year-old (range: 29-74). Five patients had stage IV at diagnosis and the most common histologic subtype was LUAD (5). Six patients had first grade family history of cancer with a median of 2 family members (range: 1-4) and 2 patients had prior history of cancer. Tumor somatic profile in LC was obtained in 6 patients, consisting on a ROS-1 rearrangement in one patient and EGFR mutations in 5 patients (exon 19 deletion in 3 patients and missense mutations in 2 patients, p.(Gly719Ala) at exon 18 and p.(Leu858Arg) at exon 21) and in 1 patient was unknown. All patients with mutant EGFR received EGFR tyrosine kinase inhibitors (TKI) with a median PFS of 29 months (95% CI 0-67). Four had partial response and one a complete response to TKI treatment. At disease progression, one patient had small cell transformation and another acquired EGFR T790M mutation. Median lines of treatment were 4 (range 1-6). Two patients are alive at data cut off. Median OS is 47 months (95% CI 32-62).
Conclusion
Patients diagnosed with LC and LFS are enriched with actionable genomic alterations and have an earlier onset of the disease. Clinical outcome of patients with EGFR mutations and LFS did not differ from EGFR mutated LC patients who do not carry TP53 germline mutations.
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-49 - Targeting STAT3-Positive Reactive Astrocytes with Silibinin in the Therapeutic Landscape of Non-Small-Cell Lung Cancer with Brain Metastases (Now Available) (ID 1336)
10:15 - 18:15 | Author(s): Joan Brunet
- Abstract
Background
Silibinin is a bioactive flavonolignan extracted from milk thistle (Silybum marianum) and is a direct inhibitor of STAT3 – with high affinity to both the Src homology-2 domain and the DNA-binding domain of STAT3. Pre-clinical data indicate that blocking STAT3 signaling in reactive astrocytes, a major component of the brain metastasis microenvironment, can decrease the number and size of brain metastases (BM).
Method
We present data on all patients diagnosed with BM from non-small cell lung cancer (NSCLC) from the Cancer Register of the Hospital Universitari Dr. Josep Trueta during 2013–2017. Age, gender, histology, and treatment in patients were recorded. During this period, some patients received compassionate use of Legasil®, a commercially available silibinin-based nutraceutical, in addition to standard oncologic treatment. The data cut-off for survival analysis was 28th March 2019.
Result
We identified 221 patients with NSCLC and BM. Median age: 62 y (range: 32–88 y); male: 161 (72.9%). Synchronous BM were observed at the diagnosis of primary lung cancer in 133 (60.2%) patients. Differences in median overall survival (mOS) were detected by histology subtype: adenocarcinoma (66.1%)=4.6 m, squamous (17.6%)=1.8 m, not otherwise specified (16.3%)=2.2 m, p=0.000003. Treatment effects on mOS are summarized in Table 1. In the subgroup of patients that received brain radiotherapy in addition to systemic therapy for BM, differences were maintained between patients that received Legasil® (n=15) or not (n=64):28.5 months vs 6.3 months (p=0.000052).
Table 1 Treatment % mOS
(without)mOS
(with treatment)p-value Brain radiotherapy 53.8% 1.9 m 5.1 m < 0.000001 Systemic therapy 52% 1.6 m 6.9 m < 0.000001 Brain surgery 5% 3.2 m 15.5 m =0.000127 Silibinin supplementation 8.1% 3.5 m 22.8 m =0.000001
Conclusion
Our data indicate that silibinin supplementation could contribute to the control of BM in patients with NSCLC. Further evaluation of silibinin, or other STAT3 inhibitors, in clinical trials is warranted in this setting.
