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Oscar Arrieta



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    MA02 - Improving Outcomes for Patients with Lung Cancer (ID 895)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 10:30 - 12:00, Room 201 BD
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      MA02.08 - The Effect of Nabilone on Appetite, Nutritional Status, and Quality of Life in Lung Cancer Patients: A Randomized, Double-Blind Clinical Trial (ID 13428)

      11:15 - 11:20  |  Author(s): Oscar Arrieta

      • Abstract
      • Presentation
      • Slides

      Background

      Over one half of the patients diagnosed with advanced lung cancer experience anorexia. In addition to its high incidence, cancer-induced anorexia promotes the development of the anorexia-cachexia syndrome, which is related to poor clinical outcomes. Recently, drugs derived from cannabinoids, such as Nabilone, have been recognized for their appetite improvement properties; however, clinical trials to support their use in cancer patients are necessary.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      This is a randomized, double-blind, placebo-controlled clinical trial to assess the effect of Nabilone vs. placebo on the appetite, nutritional status, and quality of life in patients diagnosed with advanced Non-small cell lung cancer (NSCLC) (NCT02802540).

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 65 patients from the outpatient clinic at the National Institute of Cancer (INCan) were assessed for eligibility and 47 were randomized to receive Nabilone (0.5 mg/2 weeks followed by 1.0 mg/6 weeks) or placebo. After 8 weeks of treatment, patients who received Nabilone increased their energy intake (342-kcal) and had a significantly improvements in Quality of life parameters.

      diapositiva1.jpgdiapositiva1.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      Nabilone is an adequate and safe therapeutic option to aid in the treatment of patients diagnosed with anorexia. Larger trials are necessary in order to draw robust conclusions in regard to its efficacy in lung cancer patients.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    MA08 - Clinical Trials in Brain Metastases (ID 906)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 15:15 - 16:45, Room 203 BD
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      MA08.02 - Prophylactic Cranial Irradiation Reduces the Risk of Brain Metastases in High-Risk Lung Cancer Patients: EGFR and ALK Mutations (ID 13496)

      15:20 - 15:25  |  Presenting Author(s): Oscar Arrieta

      • Abstract
      • Presentation
      • Slides

      Background

      Prophylactic Cranial Irradiation (PCI) is considered standard-of-care for small-cell lung cancer, due to consistent findings of a reduced risk of developing brain metastases (BM) and a survival benefit. The role of PCI for patients with Non-small cell lung cancer (NSCLC) is less well established, since a clear survival benefit has not been identified, although high-risk subgroups have been identified, including patients with driver mutations and with elevated carcinoembryonic antigen (CEA) levels.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We assessed the use of PCI compared to observation in patients with stage IV NSCLC (NCT01603849). PCI dose was set 25 Gy/10 f. An amendment to the original record was requested so that patients who received PCI after January 2016 had hippocampal sparing. Primary end point was Intracranial Progression-Free survival (IPFS), secondary was overall survival (OS).

      4c3880bb027f159e801041b1021e88e8 Result

      84 patients were included, 43 were randomized to observation and 41 to PCI. 83.3% had a driver mutation (DM). Baseline characteristics were well balanced among groups. Median IPFS was 21.0 months (95%CI 16.2-25.9). Factors which were independently, positively associated with IPFS included ECOG (p=0.012) and therapeutic arm (p=0.006). PCI was associated with lower odds of progression to CNS (OR:0.16 (0.04–0.53), p=0.006).Cumulative incidence of BM at 1-yr was higher among patients without PCI (22% vs. 3%, p<0.001). Relative risk for IPFS in patients with DM was 0.29 (0.10-0.82, p=0.01), HR for OS was 0.48 (0.20-1.16, p=0.098). Median OS was higher in the PCI group compared to control [42.8 (95%CI: 28.1–57.6) vs. 25.9 (95%CI: 17.7 – 34.2)] months. Last, PCI was associated with lower hazards of death, 0.47 (0.24–0.95), p=0.035.rt-prof figure.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      PCI significantly increases IPFS and decreases risk of death in patients with advanced NSCLC, without neurocognitive impairment or decreased QoL. This intervention appears to be particularly useful for patients with good performance status and driver mutations. PCI increased IPFS without neurocognitive impairment or decreased QoL.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    MA25 - Oligometastasis: Defining, Treating, and Evaluating (ID 929)

    • Event: WCLC 2018
    • Type: Mini Oral Abstract Session
    • Track: Oligometastatic NSCLC
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 13:30 - 15:00, Room 203 BD
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      MA25.10 - Complete Response by PET-CT After Radical Treatment in Oligometastatic Non-Small Cell Lung Cancer Predicts Longer Survival   (ID 14232)

      14:35 - 14:40  |  Presenting Author(s): Oscar Arrieta

      • Abstract
      • Presentation
      • Slides

      Background

      Evidence is rapidly accumulating for the use of radical treatment approaches for patients with oligometastatic Non-small cell lung cancer (NSCLC). Several limitations remain, however, to further strengthen the use of radical therapy as opposed to standard maintenance therapy, including a lack of robust markers to predict patient response. In this study, we assessed the utility of reaching a complete response (CR) by PET-CT in patients with oligometastatic disease after radical treatment (NCT02805530).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We included patients with stage IV NSCLC who presented with ≤5 synchronous, any-site metastases (oligometastatic disease) as assessed by PET-CT. Patients received 4 initial cycles of systemic treatment. Following, patients were evaluated by PET-CT and those with stable disease and partial response received radical treatment to the primary site and metastases (surgery, radiotherapy, chemotherapy plus radiotherapy, radiofrequency and SBRT alone or in any combination). Response to radical treatment was evaluated by PET-CT. Maintenance treatment was permitted.

      4c3880bb027f159e801041b1021e88e8 Result

      37 patients were included in the analysis. Mean age was 55.7. At diagnosis 43.2% of patients presented with CNS metastases. After 4 cycles of first-line therapy, 100% of patients received treatment to the primary site, while 83.8% also received therapy to metastases. Following radical treatment, 19 (51.4%) patients achieved a CR by PET-CT, while 18 (48.6%) had a partial response (NON-CR). Median PFS was 26.2 months (95%CI 12.2-40.1), and was positively affected by CR by PET-CT (NR vs. 14.3 [95%CI 11.9-16.7]; p<0.001). Median overall survival (OS) was NR. OS was also positively affected by CR by PET-CT (42-month survival: 82.5%±18 for CR vs. 34.4%±28 for NON-CR by PET-CT; p=0.01).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Patients with oligometastatic NSCLC who undergo radical treatment and reach a CR by PET-CT show a significant improvement in survival outcomes. Our results suggest that CR by PET-CT could serve as a surrogate marker for prolonged survival in this patient sufigure rc petct.pngbgroup.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.01-03 - Effect of Prophylactic Cranial Irradiation on Cognitive Function and QoL in NSCLC Patients at High Risk of Brain Metastases (ID 14166)

      16:45 - 18:00  |  Presenting Author(s): Oscar Arrieta

      • Abstract
      • Slides

      Background

      Up to 50% of NSCLC patients develop brain metastases (BM). Prophylactic Cranial Irradiation (PCI) is a potentially useful strategy to prevent this event, although its use remains controversial due to inherent risks. Therefore, actions such as dose adjustment for Whole Brain Radiotherapy (WBRT), or hippocampal-sparing techniques have been explored. We evaluated the impact of PCI on cognitive function and Quality of Life (QoL).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Within the clinical trial NCT01603849 we evaluated a total of 84 histologically-confirmed NSCLC patients with high risk of developing BM (adenocarcinomas harboring oncodrivers (EGFR or ALK) and/or carcinoembryonic antigen (CAE) level at diagnosis ≥20 pg/mL). Patients were randomized 1:1, 41 to receive PCI and 43 to observation. Cognitive function (CF) was evaluated before and after treatment and at 6, 9 and 12 months with Mini Mental State Examination (MMSE). Reliable Change Index was used to evaluate the effect on CF. QoL was assessed through the European Organization for Research and Treatment of Cancer (EORTC-QLQ-30). Differences between groups were compared with Mann Whitney U and Friedman test. OS was estimated from the first MRI assessing the absence of BM until death/last follow-up with Kaplan-Meier and compared with Log-Rank test.

      4c3880bb027f159e801041b1021e88e8 Result

      83.3% of patients presented an EGFR-mutation (n=60) or ALK-rearrangement (n=6). Median OS was 42.8 vs. 25.9 months among patients with or without PCI (p=0.031). MMSE scores and median score values for global QoL, fatigue and cognitive functioning did not differ among groups or at baseline and follow-up. There were also no differences in percentual change at 1-yr (Table).

      Clinical changes (MMSE)

      3 months

      6 months

      9 months

      1 yr

      n/N (%)

      n/N (%)

      n/N (%)

      n/N (%)

      Without PCI

      Without Changes

      38/43 (88.4)

      34/42 (81)

      34/42 (81.0)

      29/37 (78.4)

      Cognitive Deterioration

      0/43 (0)

      2/42 (4.8)

      0/42 (0)

      0/37(0)

      Cognitive Improvement

      5/43 (11.6)

      6/42 (14.2)

      8/42 (19.0)

      8/37 (21.6)

      With PCI

      Without Changes

      39/41 (95.1)

      31/34 (91.2)

      31/34 (91.2)

      27/31(87.1)

      Cognitive Deterioration

      1/41 (2.4)

      0/34 (0)

      0/34 (0)

      1/31(3.2)

      Cognitive Improvement

      1/41 (2.4)

      3/34 (8.8)

      3/34 (8.8)

      3/31 (9.7)

      Baseline

      3 months

      6 months

      9 months

      1 yr

      p-Value (*)

      Diff. at 1 yr

      Median (IQR)

      Median (IQR)

      Median (IQR)

      Median (IQR)

      Median (IQR)

      Median (IQR)

      Global QoL

      Without PCI

      66.7 (50.0 - 83.3)

      66.7 (50.0 - 83.3)

      66.7 (64.6 - 83.3)

      83.3 (66.7 - 85.4)

      83.3 (75.0 - 87.5)

      <0.001

      8.3 (0.0 - 29-2)

      With PCI

      66.7 (50.0 - 83.3)

      66.7 (50.0 - 83.3)

      66.6 (66.7 - 83.3)

      83.3 (66.7 - 83.3)

      83.3 (75.0 - 83.3)

      <0.001

      0.0 (0 - 25.0)

      p-Value (diff between groups)

      0.956

      0.786

      0.903

      0.172

      0.595

      0.791

      Fatigue

      Without PCI

      22.2 (11.1 - 44.4)

      33.3 (22.2 - 44.4)

      22.2 (11.1 - 44.4)

      22.2 (11.1 - 44.4)

      22.2 (11.1 - 33.3)

      <0.001

      0.0 (-22.2 - 0.0)

      With PCI

      22.2 (5.6 -33.3)

      33.3 (11.1 - 33.3)

      22.2 (8.3 - 33.3)

      22.2 (8.3 - 33.3)

      22.2 (0.0 - 33.3)

      <0.001

      0 (0 - 0)

      p-Value (diff between groups)

      0.493

      0.132

      0.942

      0.931

      0.93

      0.553

      Cognitive

      Without PCI

      83.3 (66.7 - 100.0)

      83.3 (66.7 - 100.0)

      83.3 (66.7 - 100.0)

      73.3 (83.3 - 100.0)

      73.3 (83.3 - 100.0)

      0.004

      0 (0 - 0)

      With PCI

      83.3 (66.7 - 100.0)

      83.3 (66.7 - 100.0)

      83.3 (66.7 - 100.0)

      91.7 (70.8 - 100.0)

      83.3 (83.3 - 100.0)

      0.017

      0.0 (0.0 - 0.0)

      p-Value (diff between groups)

      0.854

      0.983

      0.521

      0.411

      0.757

      0.734

      8eea62084ca7e541d918e823422bd82e Conclusion

      PCI was not associated with significant differences in MMSE and QoL scores, furthermore there were no differences when assessing specific subscales (e.g. fatigue and cognitive functioning). These results along with the clinical benefit in OS highlight the benefit of this approach particularly among patients at high risk of developing BM.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P1.09 - Pathology (Not CME Accredited Session) (ID 941)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.09-21 - Circulating Tumor DNA Improves Genotypification and Detection of Targetable Alterations in Selected Lung Cancer Patients (ID 12218)

      16:45 - 18:00  |  Author(s): Oscar Arrieta

      • Abstract
      • Slides

      Background

      Several studies have shown that NSCLC genomic background among Hispanics differs from other populations. The finding of low frequency genomic alterations in cfDNA to increase diagnostic accuracy in NSCLC could refine the treatment. We hypothesized that cfDNA can be an alternative or complement for detection of low frequency genomic targets. We aimed to understand the landscape of cfDNA-identified genomic drivers in a cohort of patients (pts) with NSCLC of Hispanic ancestry.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We collected data from 51 Hispanic pts (Mexico and Colombia) with advanced NSCLC (Stage III/IV) who previously underwent tissue screening for ALK, EGFR, and ROS1. CfDNA was extracted from plasma and analyzed by a commercial NGS test (Guardant360â) which detects genomic alterations (alts) in up to 73 genes.

      4c3880bb027f159e801041b1021e88e8 Result

      Median age was 56 years (31-83). Most pts were female (64.7%) and never smokers (76.5%). 94% of cases (48/51) had cfDNA detectable alts with a mean number of 3.37 cfDNA alts per test (range, 1 -10). Of the 48 pts with cfDNA genomic alts, 23 (47.9%) had a known genomic driver (EGFR (27.4%), TP53 (13.7%), ALK (7.8%), KRAS (5.8%), and BRAF (3.9%)). Interestingly, cfDNA was able to detect some genomic alts previously undetected by tissue biopsy (either due to false negatives or to technical limitations such as insufficient or low-quality DNA). In the case of EGFR, 12 pts had EGFR alts through cfDNA which were previously undetected by tissue biopsy. Similarly, cfDNA detected 3 alterations in ALK which were previously undetected by tissue sample. Of 48 pts, 35.4% were switched to a targeted therapy as a result of alts detected through cfDNA, with adequate responses: disease control rate was 82.4% (partial response 47.2% and stable disease 35.2%) and progression free survival was 7.4 months (95%CI 2.6-28.1).

      8eea62084ca7e541d918e823422bd82e Conclusion

      In a selected population of young Hispanics (especially never smokers and women) with NSCLC the use of comprehensive cfDNA analysis allowed a treatment change in 35% of the cases. Our data confirms the usefulness of Guardant360â as non-invasive panel to identify genomic alts in cfDNA.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P1.15 - Treatment in the Real World - Support, Survivorship, Systems Research (Not CME Accredited Session) (ID 947)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.15-04 - Practice Patterns Regarding Multidisciplinary Cancer Management for NSCLC and implemetantion: Results of National Survey in México (ID 14374)

      16:45 - 18:00  |  Author(s): Oscar Arrieta

      • Abstract

      Background

      To manage patients with advanced lung cancer in the most effective way, experts from different disciplines need to be engaged. This has resulted in introduction of the multidisciplinary team (MDT) approach. Because of these advantages, current clinical guidelines recommend discussing the diagnostic and therapeutic plan with an MDT for localized or locally advanced Non-Small Cell Lung Cancer (NSCLC). However, studies suggest despite the advantages of multidisciplinary care, the proportion of new lung cancer diagnoses that are formally discussed in Lung Cancer MDM are disappointing low, in the order of 28–29%. An Australian survey suggests that only one third of hospitals have a multidisciplinary team.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      However, it is unclear how specialists view current evidence about multidisciplinary team (MDT) approach and how they would incorporate into practice. We sought to understand specialist opinions about evidence regarding treatment of NSCLC and how this translates into clinical practice implementation.This study was conducted to explore specialist opinions about multidisciplinary team approach of NSCLC, how this translates into practice and the implementation in Mexico.

      4c3880bb027f159e801041b1021e88e8 Result

      We collected a total of 60 completed responses (50%), 77% were medical oncologist, 7% surgical oncologist and 17% radiation oncologists. Of these 34% mainly worked in private and 66% in public healthcare Systems. Seventy two percent of all physicians were < 40 years, 25% between 40 and 50 years of age and 22% were 50 years of age or older. Young doctors (up to 5 years of service) accounted for 45 %, with a median length of practice of 12 years. More than two-thirds of physicians were male. Approximately 58% of respondents stated that exist a MDTs for NSLC in their institutions. The Core members of the multidisciplinary cancer team usually include an oncologist (medical, surgical, radiation), pathologist and radiologist in the 65% of the teams. Approximately 55% of respondents stated that MDTs met regularly. Forty two of survey responders do not have a MDT but can discusses new cases directly with surgical oncologist o radiologist.

      8eea62084ca7e541d918e823422bd82e Conclusion

      While multidisciplinary care has emerged as the standard of care for lung cancer management. The challenge for the future is how to more fully integrate multidisciplinary care into the management of all patients with lung cancer in México.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.01 - Advanced NSCLC (Not CME Accredited Session) (ID 950)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.01-11 - Characteristics of Non-Small Cell Lung Cancer: Differences by Sex and Hormonal Status in a Hispanic Population (ID 12789)

      16:45 - 18:00  |  Author(s): Oscar Arrieta

      • Abstract
      • Slides

      Background

      Non-small Cell Lung Cancer (NSCLC) appears to be a different disease between women and men. Clinical features and lung cancer behavior by sex and particularly by hormonal status has been poorly approached. We describe the differences in NSCLC by sex and by hormonal status among women in a Hispanic population.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We performed a retrospective study among NSCLC patients from the National Cancer Institute of Mexico. We assessed clinic-pathological (tobacco, wood smoke and asbestos exposure, histology, disease stage, ECOG, Body Index Mass, Metastases sites) and molecular characteristics (EGFR and KRAS mutation profile). Overall survival (OS) according to sex and hormonal status were estimated using the Kaplan-Meier method and compared using the Log-rank test. Multivariate cox-proportional analysis was performed adjusting for clinical and statistically relevant features.

      4c3880bb027f159e801041b1021e88e8 Result

      Among the 1,104 patients 52.7% were men and 47.3% were women. Compared to men, women were more likely to be non-smokers (68% vs. 23%, p<0.001), reported higher frequencies of wood-smoke exposure (50% vs 28.2%, p<0.001), and of EGFR-sensitizing mutations (38.8% vs 18.7%, p<0.001), had a better ECOG performance (<2) (76.2% vs 69.9%, p=0.020) and showed a higher frequency of BMI ³25 (48.4% vs 41.5% p=0.003). Likewise, women, showed better OS (p=0.021) compared to men as well as overweight patients (vs. normal or obese patients) (p=0.045), non-smokers (p=0.002) and patients with lower ECOG status (p=0.006). Differences were found also when considering hormonal status. Postmenopausal women showed higher wood-smoke exposure (52.5% vs 41.7%, p=0.037) and wood-smoke exposure index (113.2% vs 50.6%, p=0.006) as well as tobacco smoking exposure index (19.8 vs 10.2, p=0.017) compared to premenopausal younger women who exhibited higher frequencies of exposure to asbestos (16.7% vs 7.0%, p=0.001) compared to postmenopausal. OS was better in postmenopausal women compared to premenopausal (31.1 vs 19.4 months, p=0.046). No differences were found between premenopausal and postmenopausal women stratified by EGFR mutation status regarding their clinic-pathological and molecular characteristics, neither in the OS.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our results support the differences in lung cancer presentation by sex and also by hormonal status. It is important to highlight that wood-smoke exposure and tobacco consumption were associated with hormonal status. Furthermore, premenopausal women (which showed a younger age at diagnosis) showed a worse OS regardless of other molecular features (e.g. EGFR, KRAS) which highlights the need of investigating in detail hormonal profiles when considering the clinical approach of NSCLC diagnosis and treatment.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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      P2.01-96 - Dysgeusia Associated with Nutritional and Quality of Life Parameters in Non-Small Cell Lung Cancer Patients Naïve to Chemotherapy (ID 13369)

      16:45 - 18:00  |  Author(s): Oscar Arrieta

      • Abstract
      • Slides

      Background

      Dysgeusia (taste alteration) has been reported in more than 50% of patient undergoing chemotherapy, however, it can be present before treatment, and it can be associated with nutritional and quality of life parameters.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We evaluated 65 patients naïve to chemotherapy, the alteration of taste by self-reporting questionnaire and through rinse stimuli to identify detection and recognition thresholds of umami, sweet and bitter taste; as well as, their association with nutritional and quality of life parameters.

      4c3880bb027f159e801041b1021e88e8 Result

      Dysgeusia, perceived as a different taste from food was reported in 35% of patients. Those with dysgeusia presents less mean of weight (p=0.059), less lean body mass (p=0.027), higher Fat Mass (p= 0.027), less consumption of protein (0.059), iron (0.022) and sodium (0.034). Patients with dysgeusia reported unfavorable score in functional scales of Health Related Quality of Life (HRQL), than those without dysgeusia; including, Role Functioning (p=0.182*), emotional functioning (p=0.038), cognitive functioning (p=0.017) and social functioning (0.325*). And, the same for symptomatic scales: fatigue (p=0.016), nausea and vomiting (p=0.021), pain (p=0.133*), appetite loss (p<0.001) and constipation (p=0.005).

      diapositiva1.jpgdiapositiva2.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      Conclusion: Patients with non-small cell lung cancer present dysgeusia before treatment and affect clinical parameters, food consumption habits and quality of life. Nutritional- care must be provided opportunely.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.04 - Immunooncology (Not CME Accredited Session) (ID 953)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.04-01 - Associations Histological Subtype of Lung Adenocarcinoma and Programmed Death Ligand 1 (PD-L1) Expression in Tumor Cells. (ID 12995)

      16:45 - 18:00  |  Author(s): Oscar Arrieta

      • Abstract
      • Slides

      Background

      The analysis by immunohistochemistry (IHC) of the programmed cell death-ligand 1 (PD-L1) protein expression is the most extensively explored biomarker for response to immunotherapy in non-small cell lung cancer (NSCLC). However, there are differences concerning diverse IHC assays and cut-off criteria: Pembrolizumab with the 22C3 assay with cut-off ranges of >1%, 1-49% and >50%; and Nivolumab with the 28-8 assay and ranges of <1%, 1-5%, 5 -10% and >10%. Furthermore, there is lack of information regarding the association between the histological subtype of adenocarcinoma and PD-L1 expression. In this work, we assessed the frequency of PD-L1 expression according with to histological subtype of adenocarcinoma.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      PD-L1 expression was assessed using the PD-L1 IHC 22C3 pharmDx immunohistochemistry assay (Dako North America, Inc.). We correlated histological subtype of adenocarcinoma with the frequency and intensity of PD-L1 expression, smoking history, EGFR and ALK status.

      4c3880bb027f159e801041b1021e88e8 Result

      Tissue samples from one hundred and sixty-two were analyzed, of which 33 (20.4%) were excluded due to insufficient material for PD-L1asessment. Among them, 106 patients (71,55%) were female, the median age was 63 years (range 31-86 years), 69 (53.5%) were never-smokers with no exposition to wood smoke or asbestos (79,61.2% and 117, 90.7% respectively). Among the 129 adenocarcinomas, 31.0% were acinar histological subtype; 27.1% solid, 17.1% papillary, 3.9% lepidic, 1.6% micropapillary and 54.3% had a moderated tumor differentiation grade. According to PD-L1 score, 49 (38%) of the patients were classified as negative (PD-L1<1%), 71(55%) as poor PD-L1 expression (1 - 49%), and 9 (7%) as strong PD-L1 expression (≥50%). According to the IASLC/ATS adenocarcinoma histological subtype was associated with PD-L1 expression (p=0.003). Solid and acinar adenocarcinomas were more likely to present strong PD-L1 expression (55.6% & 33.3%, respectively) compared to lepidic, papillary, micropapillary and unspecified tumors, which presented a strong PD-L1 expression in up to 11.1%. Median PFS to first line therapy was 10.3 (95% CI: 6.1–14.5) months. Tobacco exposure was the only factor independently associated with an increase in the hazard of progression to first line therapy (either CT or TKI) from any cause among NSCLC patients (HR, 95% CI: 1.56-12.1). The median OS was 41.9 (95% CI: 10.9–72.9) months. Median OS differences were not found among PD-L1 (negative vs. positive: 60.6 vs. 31.3 months, p=0.685).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Patients with adenocarcinoma tumors, solid histological subtype and poor differentiation grade can be more benefited with a PD-1 based immunotherapy. PD-L1 score can be a predictor factor for the response to first line chemotherapy.

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    P2.06 - Mesothelioma (Not CME Accredited Session) (ID 955)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 2
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.06-02 - Feasibility of Intensity Modulated Radiotherapy After Pleurectomy/Decortication for Malignant Pleural Mesothelioma Patients (ID 12000)

      16:45 - 18:00  |  Presenting Author(s): Oscar Arrieta

      • Abstract
      • Slides

      Background

      Treatment strategies for patients with malignant pleural mesothelioma (MPM) include pneumectomy followed by radiation with considerable efficacy, although post-surgical morbidity and mortality are frequent. Recently, more conservative surgical approaches have been implemented, including Pleurectomy/Decortication (P/D), which spares the lung tissue while removing the malignant pleura and visible tumor. Although this approach significantly reduces surgical morbidity, it poses a challenge for post-surgical radiotherapy, as the risk of developing radiation pneumonitis is high. In this feasibility study we evaluated the loco-regional control and toxicity profile in patients with MPM treated with induction chemotherapy followed by P/C and Intensity Modulated Radiotherapy (IMRT) to the entire thoracic cavity.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with MPM treated from October 2011 to February 2014 were screened for inclusion. All patients underwent 4 cycles of induction chemotherapy with cisplatin/gemcitabine or cisplatin/pemetrexed without progression followed by P/D. Thereafter, patients received IMRT to the thoracic cavity (50.4-54 Gy in 28-30 fractions), treated with 9-11 non-coplanar fields.

      4c3880bb027f159e801041b1021e88e8 Result

      A total of 20 patients were screened for inclusion, from these, 13 patients were included in the final analysis. The median age was 61.3 ±10.3 years; 69.2% (9/13) were classified as low risk according to the European Organization for Research and Treatment of Cancer prognostic group. From the 13 patients, 12 (92.3%) had a histological diagnosis of epithelioid mesothelioma, while one patient (7.7%) presented with a sarcomatoid histology. Partial response to chemotherapy was observed in 61.5% (8/13) and stable disease in 38.5% (5/13). After P/D, only 23% (3/13) had residual macroscopic disease. The median follow-up was 23.6 months (7.5-44.7). Nine patients had recurrence or progression (6 distant [67%] and 3 loco-regional recurrences [33%]). 2-year Progression Free Survival was 31.3% (95%CI [8.72-57.51]). Only one patient died due to hepatic metastases. Any grade Pneumonitis was reported in 69.2% (9/13), however only 22.2% (n=2) of patients presented grade ≥3 pneumonitis. The V5 of the contralateral lung was above 70% and the V20 of the total lung was 45% in these patients. No IMRT-related deaths were observed throughout the study.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Results from this pilot study show that it is feasible to administer IMRT to patients who have undergone P/D while maintaining an adequate toxicity profile. In our study pulmonary toxicity was frequent; however there was only one event of grade 4 pneumonitis, meanwhile the loco-regional control using this treatment modality shows great promise. However, a larger study with a more robust sample size is required to draw strong conclusions.

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      P2.06-26 - Ribonucleotide Reductase Subunit M1 but not M2 is Associated to Better PFS in Patients with Advanced Stage Mesothelioma (ID 13947)

      16:45 - 18:00  |  Author(s): Oscar Arrieta

      • Abstract
      • Slides

      Background

      Ribonucleotide reductase M1 (RRM1) is the catalytic subunit of ribunucleotide reductase, the enzyme responsible for de novo synthesis of most of the deoxyribonucleotides. Low-level expression of RRM1 has been associated to better prognosis in patients with solid tumors. A previous study identified that RRM1 is a predictor for freedom from recurrence in patients with malignant pleural mesothelioma (MPM) undergoing induction chemotherapy following extrapleural pneumonectomy.

      Ribonucleotide reductase subunit M2 (RRM2) is associated with apoptosis, cell proliferation, invasion and migration. Some studies have suggested that expression of RRM2 could play a role in tumorigenesis of several cancers; however, its role in MPM is unknown.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      The expression of RRM1 and RRM2 was assessed by immunohistochemistry using commercial antibodies. Quantitative analysis was performed using computerized image software, namely digital pathology. All of the samples were scanned and the median value of each marker was used as the cutoff value, >median value corresponds to high expression level and <median value to low expression level. The expression levels were determined in samples from 91 patients with advanced MPM, who had received gemcitabine-based chemotherapy. We correlated these data with clinical parameters and disease outcome (Progression Free Survival [PFS]).

      4c3880bb027f159e801041b1021e88e8 Result

      Our study population presented a median age of 60 years (53 -71 yrs), most were male 64.8 %, with asbestos exposure in 57.2% of cases and epithelioid histology in 85.7%. Almost half of the patients received gemcitabine as first-line treatment (n=43; 47.3%). Overall PFS was 14.1 months (95% CI 9.8–18.4 months,) while PFS in patients receiving gemcitabine treatment was 6.8 months (95% CI 5.4–8.2 months). Several factors were associated to an improved PFS, including female vs. male sex (7.2 vs 6.6 months, p=0.062) and epithelial vs. sarcomatoid histology (7.2 vs 3.8 months, p=0.035) after gemcitabine treatment in univariate analysis. In the multivariate analysis, sex (HR 3.06, p=0.085) and no wood-smoke exposure (HR 2.55, p=0.092) were independently associated to gemcitabine treatment. Patients with high expression levels of RRM1 showed better PFS compared to patients with low expression levels (7.6 vs 5.5 months, p=0.049) in univariate analysis; with a HR of 0.204 (0.050–0.831) p=0.026 in multivariate analysis. Conversely, the M2 subunit (RRM2) did not show any significant associations (7.6 vs 6.6 months, p=0.363).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our results suggest that high protein expression levels of RRM1 could potentially serve as a biomarker of response to gemcitabine treatment in patients with advanced stage MPM.

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    P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.13-11 - EGFR Amplification and Sensitizing Mutations Correlates with Survival from Erlotinib in Lung Adenocarcinoma Patients (MutP-CLICAP¶) (ID 14305)

      16:45 - 18:00  |  Author(s): Oscar Arrieta

      • Abstract

      Background

      Tumor heterogeneity causes different EGFR mutation abundances, and is believed to be responsible for varied progression-free survival (PFS) in lung adenocarcinoma (ADC) patients receiving EGFR-TKI treatment. EGFR amplification and its common presence in EGFR mutant allele might be determined by the EGFR copy number variation. Examination of EGFR amplification status in EGFR mutant patients could predict the efficacy of EGFR-TKI treatment

      a9ded1e5ce5d75814730bb4caaf49419 Method

      72 lung ADC patients, who harbored EGFR activating mutations and received erlotinib as first line treatment, were examined for EGFR amplification by FISH. We analyzed the relationship between the EGFR mutational status and copy number profile with clinical outcomes including response rate, overall-survival (OS), and PFS.

      4c3880bb027f159e801041b1021e88e8 Result

      Median age was 62-yo (r, 20-87 years), 53 patients were females (73%), and 89% had common mutations. Twenty-two (30.6%) samples with EGFR activating mutations were identified as having EGFR amplification. EGFR amplification was more frequent in patients with exon 19 deletion (p=0.05) and in those with better performance status (p=0.01). Patients with EGFR gene amplification had a significantly longer PFS than those without [(25.2 months, 95%CI 22.0-38.5) vs. (12.4 months, 95%CI 5.3-19.5); p=0.002] as well as better OS [(EGFR amplified 37.8 months, 95%CI 30.9-44.7) vs. (EGFR non-amplified 27.1 months, 95%CI 12.8-41.3); p=0.009]. EGFR amplification significantly influenced the response to erlotinib (p=0.0001).

      8eea62084ca7e541d918e823422bd82e Conclusion

      EGFR amplification occurs in one third of patients with lung ADC harboring EGFR activating mutations, and could serve as an indicator for better response and survival from EGFR-TKI treatment.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P3.01 - Advanced NSCLC (Not CME Accredited Session) (ID 967)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.01-11 - Depression and Inflammation in Patients with EGFR-Mutated Non-Small Cell Lung Cancer (ID 14336)

      12:00 - 13:30  |  Author(s): Oscar Arrieta

      • Abstract

      Background

      Although depression appears to be associated with worse survival outcomes in cancer patients, the underlying mechanisms and basis of this association remain unknown. EGFR mutations have been associated with improved treatment response and prognosis in advanced non-small lung cancer (NSCLC). However, previous reports have described a positive association between this genotype and depression. This relationship could be at least partially explained by TNFa-mediated inflammation, which activates the hypothalamus-pituitary-adrenocortical (HPA) axis, leading to tryptophan depletion through the stimulation of indoleamine 2,3 dioxygenase.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      32 patients diagnosed with metastatic NSCLC with an EGFR mutation were enrolled and followed monthly. In all cases patients were evaluated using the Self-rating depression scale (SDS) and the Numeric Rating Scale (NRS) in order to obtain a detailed evaluation of the initial symptoms and a qualitative assessment of the state of depression. In parallel we measured TNFa levels in serum/plasma (MaxDiscovery™ Human TNF-α ELISA Test Kit) upon receipt of genotype report, 4 and 12 weeks after initiating the targeted therapy, and at the time of progression. We examined differences between patients with and without depression with respect to the TNFa, as well as impact on various outcomes.

      4c3880bb027f159e801041b1021e88e8 Result

      Mean age was 58.9 years (+/- 12.4), 22 (68.8%) were women and 94% had an ECOG <2. Nineteen patients (59.4%) carried a del19, 8 (25%) had L858R, 2 (6.3%) L858R+T790M, 2 (6.3%) G719S and one patient had a del19+S768I (3.1%). Median follow-up was 15.4 months (95%CI 2.8-32.0), overall survival (OS) was 28.1 months (95%CI 25.5-30.6) and median progression-free survival (PFS) to first-line TKI was 13.1 months (95%CI 9.6-16.6).37.5% (n=12) of patients self-reported depression; in 25, 9.4 and 3.1% the clinical manifestations were mild (SDS 50-59; supportive psychotherapy), moderate (SDS 60-69; requirement of antidepressants) and severe (SDS 70 and above; required hospitalization). Depression was significantly associated with moderate-to-severe basal dyspnea (p=0.043), with brain metastases (p=0.003), and poor performance status (p=0.021). The average TNF at the time of genotype report was 12.2 pg/mL (SD±4.1), and was significantly higher in those who manifested depression (p=0.03). TNF levels increased 11% at 4 weeks and 75% at 12 weeks. Depression did not influence OS or first-line PFS.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Mild to moderate depression is prevalent in patients with lung cancer harboring EGFR mutations. As previously reported, TNFa levels are elevated in patients with lung cancer and depression, particularly in the first 12 weeks post-treatment, a finding attributable to inflammation.

      6f8b794f3246b0c1e1780bb4d4d5dc53