Browsing Over 3689 Presentations
CN63 - Screening for psychosocial distress in recently diagnosed cancer patients (ID 5066)
- Eva Baillès (Escaldes-Engordany, Andorra)
Abstract
Background
Receiving a diagnosis of cancer may be associated with increased psychosocial distress. Without objective assessments, healthcare professionals tend to underestimate psychological distress, and fail in the recognition, triage and referral of distressed patients. The specific aims of this study are to identify the level and the nature of the distress.
Methods
A descriptive prospective design has been used to analyze the data of distress thermometer (DT) in initial visits in the cancer unit. Data collection was conducted by nurses over a six month period. The variables studied were: age, sex, type of tumor, intensity and causes of distress.
Results
39 patients answered the DT screening tool. On average, the participants were 58.1 years old and 64% of them were female. The most frequent diagnoses reported were breast cancer (38%) and colon cancer (26%). 41 % rated over the cut point of DT (>4) and were referred to psycho-oncology attention. Only the 48 % attended to the psychologist after referral despite the most frequent causes of distress were physical problems (85%) and emotional problems (70%). Finally, there were a statistically significant association between intensity of distress and emotional problems (r = 0,648; p < 0, 001) but not with other problematic areas (physical, family, spiritual or practical).
Conclusions
Psychosocial distress in recently diagnosed cancer patients seems to be related with emotional problems. It is important to evaluate and manage emotional distress in these patients to improve their quality of life and refer patients to the psychologist when it is necessary.
Legal entity responsible for the study
E Bailles.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
780P - Effect of neoadjuvant chemotherapy on the programmed death-1 pathway in esophageal and gastric cancer (ID 2032)
- Maria C. Svensson (Lund, Sweden)
Abstract
Background
Esophageal and gastric (EG) cancers stand for a considerable amount of cancer cases and deaths worldwide. Although addition of neoadjuvant and/or adjuvant therapy has led to an improved survival in patients with resectable tumours, there is still a great unmet need for novel treatment strategies and complementary biomarkers. This study examined the effect of neoadjuvant chemotherapy on the expression of programmed death receptor 1 (PD-1) and programmed death ligand 1 (PD-L1) in EG adenocarcinoma, as well as the associations of PD-1 and PD-L1 expression with histopathological response and clinical outcome.
Methods
Immunohistochemical expression of PD-1 on tumour-infiltrating immune cells (TIC) and of PD-L1 on tumour cells (TC) and TIC was assessed on paired pre-treatment biopsies, post-treatment resected primary tumours and a subset of paired lymph node metastases from a consecutive cohort of 148 patients with neoadjuvant +/- adjuvant treated EG adenocarcinoma.
Results
PD-1 expression was significantly higher in resected tumours and in lymph node metastases compared to biopsies, but the expression of PD-L1 TC and PD-L1 TIC was similar before and after neoadjuvant therapy. PD-1 expression was not associated with histopathological response or with survival. Positive PD-L1 TC expression in biopsies was significantly associated with histopathological response but not with survival, whereas positive PD-L1 TC expression in resected tumours signified a reduced overall survival. High PD-L1 TIC expression in biopsies, but not in resected tumours, was significantly associated with a prolonged overall survival.
Conclusions
Expression of PD-1, but not of PD-L1, is augmented after neoadjuvant treatment. Chemotherapy may however evoke more resistant subsets of PD-L1 positive TC, thus indicating a need for alternative treatment strategies in the adjuvant setting.
Legal entity responsible for the study
Lund University.
Funding
SUS Stiftelse och Donationer Fru Berta Kamprads Stiftelse Vetenskapliga rådet, Projektmedel för forsknings- och Utvecklingsarbete.
Disclosure
All authors have declared no conflicts of interest.
Welcome and introduction poll (ID 6367)
- Diana Lüftner (Berlin, Germany)
1660P - Impact of financial considerations on French physicians’ prescription choices for advanced non-small cell lung cancer (NSCLC) (ID 4118)
- Nathalie Olympios (Rouen, France)
Abstract
Background
Immune checkpoint inhibitors (ICI) have revolutionized treatment of advanced NSCLC. In France, concerns have been raised as to the financial burden of these therapies and fear that potential patients may be ruled out. The reality of budgetary restrictions implies for choices to be made considering both the quality of life these treatments procure as well as the financial burden they represent. From a physician’s point of view, due to financial constraints on public health facilities, physicians could restrain themselves from prescribing innovative expensive therapies.
Methods
This qualitative study questions the potential impact of drug prices on prescription choices made by thoracic oncologists. Ten French oncologists and two hospital pharmacists voluntarily underwent a semi-structured interview conducted by a student in an Ethics master’s degree. Interviews consisted of two distinct parts: one clinical case where treatment choices had to be made in the first-line and second-line advanced NSCLC setting and a second part consisting of open-ended questions.
Results
Qualitative analysis of the interviews brings out that immunotherapy has radically changed the history of cancer treatment but that hopes in advanced NSCLC need to be tempered. Efficacy in a real-world setting is difficult to predict and efforts need to be made to identify accurate biomarkers. Financial matters are a source of discussions between fellow physicians and clinical pharmacists but not with patients. Physicians consider they have a duty to strictly respect guidelines particularly in a French universal healthcare system.
Conclusions
Rising costs of innovative drugs in oncology is a reality that forces a reconsideration of healthcare and drug regulation systems in order to be able to provide access to innovation for all eligible patients in the French universal healthcare system. Addressing this issue with physicians provides important insight on how treatment choices are made, their expertise and their involvement in this matter. Physicians are concerned about access to innovation for their patients and consider they ought to remain aware of these issues in order to participate in healthcare arbitration discussions.
Legal entity responsible for the study
Laboratoire Ethique Médicale - Université Paris Descartes.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Practicing oncology in patients with hereditary cancer (ID 991)
- Michiel H. Strijbos (Brasschaat, Belgium)
617P - Early response evaluation and CEA response in patients treated in a Danish randomized study comparing trifluridine/tipiracil (TAS-102) with or without bevazicumab in patients with chemorefractory metastatic colorectal cancer (mCRC) (ID 5472)
- Camilla Qvortrup (Copenhagen, Denmark)
Abstract
Background
Trifluridine/tipiracil (FTD/TPI, also known as TAS-102) prolongs OS in patients with chemorefractory mCRC. Inspired by the results of C-TASK FORCE (Kuboki 2017), we designed an investigator-initiated randomized trial in the last setting in mCRC patients demonstrating improved PFS and OS in patients receiving bevazicumab combined with TAS-102 as compared to patients treated with TAS-102 alone (Pfeiffer WCGI 2019). In the last line setting half of patients will not benefit from therapy as they have PD at the first evaluation performed after 2 months of therapy. In the present study we included an early response evaluation after 1 month of therapy aiming to identify patients not having any effect of therapy. In addition, we evaluated plasma CEA as a marker of response.
Methods
The main inclusion criteria were: histologically confirmed and chemo-refractory mCRC; PD during or after therapy with FU, irinotecan, oxaliplatin, and EGFR-inhibitor (RASwt); prior treatment with bevacizumab was allowed; PS 0-1. In arm A: FTD/TPI 35 mg/m²/dose bid from days 1-5 and 8-12; in arm B the same dose of FTD/TPI with bevacizumab (5 mg/kg), days 1 and 15 of a 28-day cycle. Response evaluation performed during treatment at 4 weeks, 8 weeks, and every 8 weeks thereafter. CEA was tested at baseline and at every 2. cycle.
Results
93 patients with chemo-refractory mCRC were randomized from Sep. 2017 to Oct. 2018. The median PFS was significantly improved from 2.6 months (arm A) to 4.6 months (arm B) with a HR 0.45 (95% CI, 0.29-0.72; P = 0.001). Median OS was significantly prolonged from 6.7 months (arm A) to 9.4 months (arm B) with HR 0.55 (95% CI, 0.32-0.94; P = 0.03) (Pfeiffer WCGI 2019). Sub-group analyses including predictive markers for early progression will presented.
Conclusions
FTD/TPI in combination with bevacizumab prolong PFS and OS and is a new option in patients with chemo-refractory mCRC. Predictive markers for early progression are ongoing and will be presented.
Clinical trial identification
2016-005241-23.
Legal entity responsible for the study
Per Pfeiffer.
Funding
Servier.
Disclosure
C. Qvortrup: Research grant / Funding (institution): Servier. P. Pfeiffer: Research grant / Funding (institution): Servier; Research grant / Funding (institution): Merck. All other authors have declared no conflicts of interest.
Tailoring radiation treatment in patients with BRCA mutated tumours (ID 281)
- Brigitte Offersen (Aarhus, Denmark)
121P - AXL expression predicts poor prognosis and lack of efficacy of anti-angiogenic and anti-epidermal growth factor receptor (EGFR) agents in patients (pts) with RAS wild type (WT) metastatic colorectal cancer (mCRC) (ID 2512)
- Claudia Cardone (Napoli, Italy)
Abstract
Background
Activation of AXL receptor tyrosine kinase is a key mediator of epithelial to mesenchymal transition (EMT). AXL is overexpressed in several human cancers, including CRC.
Methods
AXL expression was assessed by immunohistochemistry in tumor samples from 346 mCRC pts treated at three Institutions and enrolled in different clinical trials (CAPRI, MACBETH, MOMA, TRIBE2). In silico data of AXL RNA levels were obtained from GSE5851 dataset, including 80 pts with advanced mCRC treated with cetuximab in a later line.
Results
AXL expression was found in 18% of cases within tumor cells, with no difference among RAS cohorts. In the RAS WT group, AXL positive pts had a worse mPFS whether treated with chemotherapy (CT) + anti-EGFR [6.2 m (CI95% 4.2- 8.2) vs 12.1 m (CI95% 10.6 – 13.6) p 0.012] or CT+anti-angiogenic agent [6.7 m (CI95% 8.9- 19.3) vs 14.1 m (CI95% 9.4– 13.0) p 0.007], whereas in RAS mutant pts no impact on PFS was observed. AXL expression correlated with worse mOS in both cohorts; notably, in RAS WT pts mOS was 19.9 m (CI95% 10.5- 29.2) vs 37.6 m (CI95% 31.1– 44.1) p 0.006]. In tumor stroma, assessable in 334 samples, AXL was expressed in 80% of cases, with no difference among RAS groups. AXL expression correlated with lower mOS in both cohorts. (Table) Intriguingly, AXL expression in tumor and stroma (+/+) correlated with shorter mOS; in particular, RAS WT pts (+/+) had a mOS of 19.9 m (CI95% 8.0- 31.7) vs (-/-) 50.1 m (CI95% 43.9- 56.2) p 0.004]. In silico analyses showed high AXL RNA levels in 50% of pts. Moreover, in this population treated with cetuximab, in the KRAS exon2 WT cohort (N = 43) AXL high pts had worse mPFS [1.9 m (CI95% 1.7 -2.0) vs 3.8 m (CI95% 0.7-6.7) p 0.59].Cohort AXL expression in tumor cells AXL expression in stroma N Negative <1% (%) Positive ≥1% (%) PFS months p value OS months p value N Negative <1% (%) Positive ≥1% (%) PFS months p value OS months p value Overall population 346 285 (82) 61 (18) 10.7 vs 8.0 0.008 32.4 vs 23.0 0.007 334 66 (20) 268 (80) 10.7 vs 8.0 0.11 41.1 vs 28.5 0.004 RAS WT (overall) 175 147 (84) 28 (16) 12.3 vs 6.6 <0.000 37.6 vs 19.9 0.006 167 33 (20) 134 (80) 15.0 vs 10.7 0.034 49.8 vs 33.5 0.031 RAS WT CT + anti-EGFR 136 114 (84) 22 (16) 12.1 vs 6.2 0.012 35.8 vs 23.0 0.087 129 18 (14) 111 (86) 14.3 vs 10.4 0.37 44.4 vs 33.5 0.11 RAS WT CT + anti-angiogenic 39 33 (85) 6 (15) 14.1 vs 6.7 0.007 44.8 vs 13.2 0.004 38 15 (39) 23 (61) 15.0 vs 11.0 0.12 50.1 vs 40.6 0.17 RAS mut (overall) CT + anti-angiogenic 171 138 (81) 33 (19) 9.6 vs 8.9 0.78 27.6 vs 23.7 0.33 167 33 (20) 134 (80) 9.7 vs 9.2 0.98 35.5 vs 24.7 0.056
Conclusions
AXL expression in tumor and stroma might have a negative prognostic relevance in mCRC. In RAS WT pts, AXL expression might represent a predictive biomarker of lack of efficacy for both anti-EGFR and anti-angiogenic agents.
Legal entity responsible for the study
Department of Precision Medicine, Università degli Studi della Campania "Luigi Vanvitelli".
Funding
AIRC MFAG-2015-ID: 7778.
Disclosure
F. Ciardiello: Advisory / Consultancy, Advisory Board: Merck KgA, Bayer, Amgen, Roche, Servier, Pfizer. E. Martinelli: Advisory / Consultancy: Merck KgA, Amgen, Bayer, Roche, Sanofi, Servier. All other authors have declared no conflicts of interest.
Invited Discussant 1119PD and 1120PD (ID 6841)
- Amanda Psyrri (Athens, Greece)
Tumour biology and pathology (ID 6603)
- Thomas Helleday (Stockholm, Sweden)
- Therese Sorlie (Oslo, Norway)
126P - Predictors of response to checkpoint inhibitors in naïve and ipilimumab-refractory melanoma (ID 4614)
- Domenico Mallardo (Napoli, Italy)
Abstract
Background
Response to checkpoint inhibitors (CI) is governed by the tumor immune environment and understanding this immune contexture can predict response. Therapeutic intervention can change this environment even in the absence of clinical response. Patients failing initial immunotherapy may respond to a second line of CI; however, these cohorts show lower overall response rates (ORR). This study identifies transcriptional signatures associated with response to first- and second-line CI monotherapy in melanoma.
Methods
CI-naïve or ipilimumab-refractory patients were treated with ipilimumab, nivolumab or pembrolizumab at the Instituto Nazionale Tumori and clinical response was evaluated by irRECIST 1.1 criteria. Pretreatment tumor biopsies (n = 82) from metastatic lesions were collected and RNA was profiled with the NanoString® IO360 gene expression panel.
Results
Compared to CI-naïve cohorts, ipilimumab-refractory cohorts had reduced ORR to nivolumab (naïve: 35%, n = 6; refractory: 20%, n = 10) or pembrolizumab (naive: 67%, n = 6; refractory: 20%, n = 10) with multiple genes differentially expressed between groups. The Tumor Inflammation Signature, an investigational 18 gene signature of suppressed adaptive immune response enriching for pembrolizumab response, was higher in responders versus non-responders in first-line (log2 fold change: 1.56, p = 0.21), but not second-line pembrolizumab (log2 fold change: 0.41, p = 0.60). First-line pembrolizumab responders had elevated MHC2 (log2 fold change: 1.35, p = 0.02) and B cell (log2 fold change: 2.14, p = 0.02) signatures. Upon stratifying the CI-naïve cohort between no prior treatment versus prior targeted/chemotherapy, the latter had increased immune expression suggesting these therapies prime the tumor immune environment.
Conclusions
Correlating patterns of tumor gene expression with clinical response can lead to the development of biomarkers enriching for CI response in both first-line and CI-refractory patients. Utilization of a clinical grade platform such as the NanoString nCounter® may speed the development of diagnostic assays used to predict and monitor patient response to immunotherapy.
Legal entity responsible for the study
The authors.
Funding
NanoString Technologies.
Disclosure
S. Ong: Full / Part-time employment: NanoString Technologies. S. Warren: Shareholder / Stockholder / Stock options, Full / Part-time employment: NanoString Technologies. A. Cesano: Shareholder / Stockholder / Stock options, Full / Part-time employment: NanoString Technologies. J.M. Beechem: Shareholder / Stockholder / Stock options, Full / Part-time employment: NanoString Technologies. P.A. Ascierto: Advisory / Consultancy: Amgen; Advisory / Consultancy: Array; Advisory / Consultancy: BMS; Advisory / Consultancy: Incyte; Advisory / Consultancy: Immunocore; Advisory / Consultancy: MedImmune; Advisory / Consultancy: IDERA; Advisory / Consultancy: Genmab; Advisory / Consultancy: Merck; Advisory / Consultancy: Roche; Advisory / Consultancy: Genentech; Advisory / Consultancy: Sandoz; Advisory / Consultancy: Syndax; Advisory / Consultancy: Sun Pharma; Advisory / Consultancy: Ultimovacs; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Novartis. All other authors have declared no conflicts of interest.
14P - Application of sonoporation to increase anticancer drug efficacy in 2D and 3D NSCLC cell cultures (ID 1568)
- Vilma Petrikaite (Kaunas, Lithuania)
Abstract
Background
In order to improve the efficacy of chemotherapy an increasing attention is given to the drug transport to tumors. Sonoporation is the application of ultrasound (US) to increase cell membrane permeability. It is thought that US induces expansion, contraction, and explosion of microbubbles (MB) thus creating pores in the cell membrane, enhancing drug delivery and efficacy. It is important to investigate this phenomenon not only into monolayer cultured cells but also into cell spheroids that imitate the biological characteristics of tumor better than 2D cell cultures. The aim of our study was to evaluate the influence of US on the efficacy of three anticancer drugs doxorubicin (DOX), 5-fluorouracil (5-FU) and paclitaxel (PTX) into 2D and 3D A549 non-small cell lung cancer cell cultures.
Methods
US pulse repetition frequency of 10 Hz and 1 MHz center frequency were generated with peak negative pressure of 0.5 MPa and 50% duty cycle. SonoVue™ MB were used. The effect of DOX on cell viability was tested by MTT assay. Spheroids were formed using 3D Bioprinting method mixing A549 cells with human fibroblasts. DOX delivery in 2D and 3D cultures was assessed using fluorescence microscopy. DOX toxicity in tumor spheroids was evaluated according to the change of spheroid size.
Results
Separately applied US and MB did not increase DOX cytotoxicity. Meanwhile, the combination of US and MB increased DOX efficacy by approximately 4% when compared to DOX alone. US exposure did not show a positive effect on DOX delivery in 2D cancer cell cultures. On the other hand, US increased DOX delivery in tumor spheroids. 15 sec. of US exposure increased DOX penetration in the edge and middle zones of spheroids from 12 to 60%. 2 min. of US exposure decreased the amount of DOX in these zones. US also increased DOX, 5-FU and PTX toxicity in cancer cell spheroids 8-, 1.2- and 1.5-fold, respectively.
Conclusions
US is a promising physical method to enhance anticancer drug efficacy, especially into 3D cell cultures. However, there is a lack of evidence about its efficacy and further studies are needed.
Legal entity responsible for the study
The authors.
Funding
Lithuanian University of Health Sciences; Kaunas University of Technology.
Disclosure
All authors have declared no conflicts of interest.