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Amanda Tufman
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Lunch & Poster Display session (ID 58)
- Event: ELCC 2019
- Type: Poster Display session
- Track:
- Presentations: 5
- Moderators:
- Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1
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100P - A new PET-CT score for locally-advanced inoperable NSCLC stage III patients treated with chemoradiotherapy (ID 580)
12:30 - 13:00 | Author(s): Amanda Tufman
- Abstract
Background
FDG-PET/CT is an integral part of staging and radiation treatment planning for patients with stage III non-small cell lung cancer (NSCLC). In this study, we analysed the correlation between different PET parameters and survival in NSCLC patients treated with chemoradiotherapy (CRT).
a9ded1e5ce5d75814730bb4caaf49419 Methods
Ninety-nine consecutive patients with NSCLC stage IIIA-B and good performance status, who underwent FDG-PET-CT before the start of CRT were analysed. Maximum standardized uptake value of primary tumor (SUVmax_PT) and range between the two most distant PET-positive (SUV≥3) lymph nodes in two directions (cranio-caudal and transversal) were analysed for their correlation with patient survival. The cranio-caudal distance was defined as A- and the transversal as B-line. The area under the ROC curve (AUC) as well as the cut-off SUVmax, A- and B-lines were calculated.
20c51b5f4e9aeb5334c90ff072e6f928 Results
Median survival for the entire cohort was 20.8 months (95% CI: 15.3-26.3). Patients with SUVmax_PT ≥ 8 had poor overall survival (OS) (19 vs. 40 months in patients with SUVmax ≥ 8 and <8, p < 0.0001). A-line was not associated with OS, whereas B-line < 3.7 cm improved OS significantly (30 vs. 16 months in patients with B-line < 3.7 and ≥3.7cm, p = 0.001). The sum of A- and B-lines with the cut-off at 6.7cm correlated with overall survival significantly (29 vs. 18 months in patients with sum < 6.7 and ≥6.7cm, p = 0.04). The PET-CT score was generated on the basis of PET parameters correlated with OS in univariate analysis. The patients were divided into 4 subgroups. The low-risk subgroup (0 points) included patients with SUVmax_PT< 8, B-line < 3.7 cm and the sum of A- and B-lines < 6.7 cm (n = 20, 21.3%). Twenty-eight patients (29.5%) had 1 point (intermediate risk), 20 (21.3%) had 2 points (high) and 26 patients (27.7%) had 3 points (very high risk). Median OS in terms of low/intermediate/high and very high risk subgroups was 40 (95% CI: 0-83)/27 (95% CI: 15-39)/26 (95% CI: 15-37) and 14 months (95% CI: 13-14), (p = 0.0001).
fd69c5cf902969e6fb71d043085ddee6 Conclusions
A new PET-CT score was developed for patients with inoperable stage III NSCLC treated with definitive CRT. Initial SUVmax_PT < 8, B-line < 3.7 cm and PET-CT score were predictors of patient long-term outcome.
b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study
The authors.
213f68309caaa4ccc14d5f99789640ad Funding
Has not received any funding.
682889d0a1d3b50267a69346a750433d Disclosure
All authors have declared no conflicts of interest.
cffcb1a185b2d7d5c44e9dc785b6bb25 -
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33P - Prognostic value of CD8-positive tumor stroma-infiltrating lymphocytes and PD-L1 positive tumor cells at initial biopsy in patients with locally advanced NSCLC treated with chemoradiotherapy (ID 581)
12:30 - 13:00 | Author(s): Amanda Tufman
- Abstract
Background
According to results of PACIFIC trial, immune checkpoint inhibitors (CPIs) are an integral part of the multimodal treatment approach for inoperable locally-advanced non-small cell lung cancer (LA-NSCLC). The purpose of this single-center study was to investigate a prognostic value of CD8-positive tumor stroma-infiltrating lymphocytes (TILs) and PD-L1 positive tumor cells at initial biopsy in patients treated with definitive chemoradiotherapy (CRT).
a9ded1e5ce5d75814730bb4caaf49419 Methods
We collected initial tumor tissue samples and reviewed the clinical characteristics of 36 LA-NSCLC patients treated at our center with definitive CRT between 2000 and 2004. The analyzed tumor tissue was taken before start of multimodal treatment. An experienced pathologist performed the immunohistochemistry analysis and interpretation. Tumor cells and CD8-positive tumor stroma-infiltrating lymphocytes were analyzed separately. Based on PD-L1 expression on tumor cells, patients were divided into three subgroups (0%, 1-5%, >5%). Two patient subgroups were defined according to CD8 expression in the tumor-surrounding stroma (low and high density: 0-40% vs. 41-100%).
20c51b5f4e9aeb5334c90ff072e6f928 Results
Thirty-six patients with LA-NSCLC were treated with definitive CRT (stage II, III and IV: 2, 30 and 4 patients). 18 (50%) patients had squamosa cell carcinoma, 14 patients (39%) adenocarcinoma and 4 patients (11%) NOS. Patients with high density of CD8 positive tumor stroma-infiltrating lymphocytes (TILS) showed a significantly reduced overall survival than patients with low density (13 vs. 19 months, one-year survival 56.5 vs. 69.2% p = 0.047); Patients without (0%) and low expression (1-5%) of PD-L1 on tumor cells showed a significantly improved overall survival compared to patients with a PD-L1 expression on tumor cells over 5% (median survival: 13.8 vs. 6.6 months, 1-year survival rate: 67.7 vs. 33.3%; p = 0.039).
fd69c5cf902969e6fb71d043085ddee6 Conclusions
High density of CD8-positive tumor stroma-infiltrating lymphocytes and PDL1 expression on tumor cells over 5% at initial biopsy correlates significantly with reduced overall survival in patients with LA-NSCLC treated with CRT.
b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study
The authors.
213f68309caaa4ccc14d5f99789640ad Funding
Has not received any funding.
682889d0a1d3b50267a69346a750433d Disclosure
All authors have declared no conflicts of interest.
cffcb1a185b2d7d5c44e9dc785b6bb25 -
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38P - Hedgehog pathway activation might mediate pemetrexed resistance in NSCLC cells (ID 330)
12:30 - 13:00 | Author(s): Amanda Tufman
- Abstract
Background
Lung cancer is the leading cause of death among all other malignancies. Despite the wide use and the high efficacy of immunotherapy, most patients with advanced or metastatic disease need chemotherapeutic treatment. Primary and acquired resistance to chemotherapeutic agents are the main cause of reduced overall survival. The Hedgehog (HH) pathway has been shown to be crucial in cell development and survival. Activated in several types of cancer it might be a potent bypass mechanism mediating chemo resistance. Thus, this study aims at investigating the role of HH signalling in chemo resistant NSCLC cells.
a9ded1e5ce5d75814730bb4caaf49419 Methods
HCC827 NSCLC cells were treated with increasing sub-lethal doses of pemetrexed and vinorelbine to produce pemetrexed and vinorelbine resistant cells. RNA was isolated from both chemo resistant and naive cells. RT-qPCR was performed to evaluated mRNA gene expression. To measure cell growth capacity we used a MTT assay to evaluate the impact of the HH-inhibitor vismodegib in naïve and chemo resistant cell lines.
20c51b5f4e9aeb5334c90ff072e6f928 Results
Pemetrexed resistant cells showed clearly increased expression levels of most of HH signalling genes. The HH transcription factors GLI1, GLI2 and GLI3 were increased 3.7, 4.3 and 3.5 fold compared to non-resistant cells. The trans-membrane HH receptor PTCH1 showed to be elevated 2.4 fold and the ligand of HH signalling SSH revealed to be expressed 5.9 fold compared to naïve cells. However, vinorelbine resistant cells did not show a significant activation of HH signalling. Supporting these results pemetrexed resistant cells treated with the HH inhibitor vismodegib showed reduced proliferation compared to naïve cells treated with vismodegib.
fd69c5cf902969e6fb71d043085ddee6 Conclusions
These are the first results of our study investigating the impact of HH signalling on chemo resistant NSCLC cells. In the case of pemetrexed resistance activation of HH pathway could play an important role to mediate this resistance. However, further investigation is needed to clarify the role of the HH pathway in NSCLC treatment.
b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study
The authors.
213f68309caaa4ccc14d5f99789640ad Funding
Has not received any funding.
682889d0a1d3b50267a69346a750433d Disclosure
All authors have declared no conflicts of interest.
cffcb1a185b2d7d5c44e9dc785b6bb25 -
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93P - Heterogeneity score in inoperable stage III non-small cell lung cancer patients treated with definitive chemoradiotherapy: A single centre analysis (ID 563)
12:30 - 13:00 | Author(s): Amanda Tufman
- Abstract
Background
Inoperable stage-III non-small cell lung cancer (NSCLC) represents a very heterogeneous disease in terms of patient and tumor characteristics. A simple heterogeneity score may help to personlize multimodal therapy.
a9ded1e5ce5d75814730bb4caaf49419 Methods
The data of 99 patients with performance status ECOG 0-1 treated with chemoradiotherapy (CRT) for inoperable stage III NSCLC, treated between 2011 and 2016 at our hospital were analyzed. Patient- and tumor-related factors were evaluated, and factors showing a significant negative association with patient survival were scored with one point each. Three subgroups with a low, intermediate and high-risk (0-1, 2-3 and 4-5 points) score were defined. The results were validated in a prospective cohort of 35 patients.
20c51b5f4e9aeb5334c90ff072e6f928 Results
Concurrent CRT was administered in 78% (n = 78) of patients and sequential CRT in 11% (n = 11), 10 Patients were treated with radiotherapy alone. 53% (n = 53) of patients received induction chemotherapy. Median overall survival (mOS) for the entire cohort was 20.8 months. Age (p = 0.020), gender (p = 0.007), cumulative tobacco pack years (PY) (p = 0.015), tumor-associated atelectasis (p = 0.004) and histology (p = 0.011) had a significant impact on survival in univariate analysis. 12, 59 and 28 patients had low, intermediate and high-risk score. MS, 1-, 2- and 3-year survival rates were as follows: not reached, 100%, 83% and 67% in the low, 22.9 months, 80%, 47% and 24% in the intermediate and 13.7 months, 57%, 25% and 18% in the high-risk score subgroup. Prospective validation of the score demonstrated one-year survival of 100% for patients in the low-risk subgroup, 93% in the intermediate-risk subgroup, and 69% in the high-risk subgroup (p = 0.100).
fd69c5cf902969e6fb71d043085ddee6 Conclusions
This simple heterogeneity score was developed for inoperable stage III NSCLC patients with good performance status receiving multimodal therapy. The score may aid physicians to infer clinical outcomes and optimize decisions concerning treatment strategies, as well as planning of prospective studies.
b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study
The authors.
213f68309caaa4ccc14d5f99789640ad Funding
Has not received any funding.
682889d0a1d3b50267a69346a750433d Disclosure
All authors have declared no conflicts of interest.
cffcb1a185b2d7d5c44e9dc785b6bb25 -
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95P - The role of patient performance status and its changes before and after completion of multimodal treatment for inoperable stage III NSCLC (ID 584)
12:30 - 13:00 | Author(s): Amanda Tufman
- Abstract
Background
The Eastern Cooperative Oncology Group performance score (ECOG-PS) is used in clinical routine to quantify patients’ general condition. We evaluated ECOG-PS before, after and its changes in the course of chemoradiotherapy (CRT) in patients with inoperable stage III NSCLC.
a9ded1e5ce5d75814730bb4caaf49419 Methods
The data of ninety-nine patients with NSCLC UICC stage IIIA/B (TNM 7th edition) were evaluated. ECOG-PS before treatment, at first follow-up and the difference was examined for their impact on overall survival (OS) from initial diagnosis and event-free survival (EFS) from the first day of radiation.
20c51b5f4e9aeb5334c90ff072e6f928 Results
Median survival for the entire cohort was 20.8 (range: 15.3-26.2) months. Before the start of multimodal treatment, ECOG-PS was 0 in 48% and 1 in 52% of patients; median OS, 1- and 2-year survival rates were 26.4 months, 85% and 53% for ECOG-PS 0 and 18.9 months, 69% and 37% for ECOG-PS 1 patients (p = 0.1). After completion of CRT 65% of patients had the same or better and 35% worse ECOG-PS: 0 in 34%, 1 in 46%, 2 in 18% and 3 in 2% of patients. Median OS, 1- and 2-year survival rates were 40.3 months, 88% and 64% for ECOG-PS 0; 19.3 months, 82% and 40% for ECOG-PS 1; 11.9 months, 50% and 28% for ECOG-PS 2 and 7.6 months, 0% and 0% for ECOG-PS 3 (p < 0.001). Deterioration of ECOG-PS after multimodal treatment significantly impaired survival in the initial ECOG-PS 0 (p = 0.005, median 19.1 vs 31.4 months) and 1 (p = 0.001, median 22.9 vs 11.1 months) subgroups. Median EFS was 9.6, 9.0, 7.9 and 3.5 months for patients with ECOG-PS 0, 1, 2, 3 after completion of CRT (p = 0.018). EFS was not affected by initial ECOG-PS but was significantly impaired by deterioration of ECOG-PS after completion of multimodal therapy with a median time of 9.4 vs 7.7 months (p = 0.049), respectively.
fd69c5cf902969e6fb71d043085ddee6 Conclusions
Deterioration of ECOG-PS after completion of primary multimodal treatment is a significant negative prognostic factor.
b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study
The authors.
213f68309caaa4ccc14d5f99789640ad Funding
Has not received any funding.
682889d0a1d3b50267a69346a750433d Disclosure
All authors have declared no conflicts of interest.
cffcb1a185b2d7d5c44e9dc785b6bb25
