Predictive Factors For Efficacy Research Articles

Nodal radiotherapy for prostate adenocarcinoma recurrence: predictive factors for efficacy.

Nodes are the second site for prostate cancer recurrence. Whole-pelvic radiotherapy (WPRT) has shown superiority over nodal stereotactic body radiotherapy (SBRT) in two retrospective cohorts. We aimed to compare both modalities and assess factors associated with treatment outcomes. This retrospective multicentric cohort study included patients from five institutions spanning from 2010 to 2022. Patients had a history of prostatic adenocarcinoma classified as N0 M0 at diagnosis with a first nodal-only pelvic castration-sensitive recurrence. Failure-free survival (FFS) was defined as the time from the end of RT to the first failure event-biochemical or imaging recurrence, or death. A total of 147 patients (pts) were analyzed, mainly treated for a recurrence after initial prostatectomy (87%), with 64 (43.5%) undergoing SBRT and 83 (56.5%) undergoing WPRT. SBRT was chosen mainly for dosimetric constraints (67%) and was associated with a lower rate of concomitant androgen deprivation therapy (ADT) prescription. With a median follow-up of 68 months [inter-quartile range (IQR) = 51], FFS was significantly lower in the SBRT group (p < 0.0001). In multivariable analysis, WPRT and ADT were associated with a longer FFS. Factors associated with a longer FFS after SBRT included associated ADT, lower prostate-specific antigen (PSA) levels, a PSA doubling time >6 months, and a Gleason score <8. SBRT was associated with a lower rate of genitourinary and gastrointestinal grade ≥2 complications. For an isolated pelvic nodal prostate cancer recurrence, SBRT is associated with a shorter FFS compared to WPRT. SBRT is often more convenient for patients and leaves further pelvic salvage options available, so it can be explored as an option for well-informed patients.

Efficacy and tolerability of 100 mg of lasmiditan for migraine: A multi-center, prospective observational real-world study in Japan.

Real-world data on the effectiveness and safety of lasmiditan, a new medication for acute migraine attacks, is necessary. We performed a prospective, observational, multi-center, real-world study. A total of 48 patients with migraine (44 females, 44.6 ± 12.9 years old) were included in this study. Twenty-three patients (47.9%) reported they were headache-free two hours after taking lasmiditan and were categorized into the responder group. In total, 44 patients (91.7%) experienced at least one side effect within two hours of taking the medication. Dizziness, somnolence, malaise, nausea, and palpitations were reported by 56.3% (n = 27), 45.8% (n = 22), 37.5% (n = 18), 20.8% (n = 10), and 14.6% (n = 7) of patients respectively. Of 48 patients, 20 (41.7%) indicated that they preferred lasmiditan to their previous acute treatment. There were no predictive factors for efficacy. This real-world study demonstrated the efficacy and safety of lasmiditan. More than 90% of patients experienced side effects from lasmiditan. Approximately 40% of patients preferred lasmiditan despite the occurrence of side effects.

Current and Upcoming Treatment Strategies After CDK4/6 Inhibitors for Patients With ER+/HER2- Advanced Breast Cancer

This industry symposium took place during the 2023 European Society for Medical Oncology (ESMO) Congress in Madrid, Spain, with a goal of presenting the latest recommendations and upcoming treatment strategies for patients with oestrogen-receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer, who experience disease progression after cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. An expert panel of clinicians explained that most patients will eventually develop resistance to endocrine therapy during the metastatic setting, and there remains a considerable margin for improvement in the second-line (2L) treatment of these patients. Data for current therapeutic options in this patient population were presented, showing that patients who have previously received CDK4/6 inhibitor therapy are often resistant to many of the available 2L therapies, including combination therapies, and that resistance appears during first-line (1L) treatment, becoming particularly significant in tumours harbouring ERS1 mutations. The recent approval of the oral selective oestrogen receptor degrader (SERD), elacestrant, was also discussed. The supporting data for this monotherapy at 2L was presented, along with changes made to the U.S. Food and Drug Administration (FDA) and European Union (EU) best practice recommendations to accommodate this therapeutic option. The panel stressed the importance of testing for ESR1 mutations at each progression during the metastatic treatment course, which is particularly relevant following the approval of elacestrant, for which ESR1 mutation is a predictive factor for efficacy.

Predictive factors for efficacy and safety of intrathecal infusion devices for oncological pain.

In an important percentage of intrathecal infusion therapy, the pain after implantation of a spinal device does not improve. Our objective is to identify factors that can predict therapeutic success and complications, developing a predictive model based on univariate and multivariate analyses. Retrospective observational study, including 132 patients with oncological pain who were implanted with a fixed-flow device for intrathecal infusion. Four time points were established for data collection and, in addition to demographic and anthropometric data, variables related to oncologic pain pathology, initiation of therapy, pain control and complications were collected. Based on univariate and multivariate analyses, we performed predictive models on efficacy and complications. The mean baseline pain intensity was VAS 7.78, and when comparing the values before implantation with those at month 1, we observed an overall decrease of 4.75 points, maintained at months 3 and 6. Nocturnal pain progressively decreased in incidence from 50.0% before implantation to 21.8%, 9.1% and 4.3% at 1, 3 and 6months. Episodic pain was present in 90.1% of the patients before implantation (7.79 episodes/day), and at 6months the incidence remained at 53.8%. Most of the patients (66.6%) had no complications related to therapy. We constructed a highly significant multivariate model for the efficacy of the therapy with a predictive capacity of 30.2% and composed of factors: absence of nocturnal pain before implantation and clinical improvement on day 2 after implant. Regarding the prediction of complications, it was not possible to achieve a significantly multivariate effective model. We identify two factors that predict therapeutic success in a multivariate model: the absence of nocturnal pain before implantation and the improvement of pain on the second day after implantation.

Efficacy of second-line chemotherapy or immune checkpoint inhibitors for patients with a prolonged objective response (≥ 6 months) after first-line therapy for recurrent or metastatic head and neck squamous cell carcinoma: a retrospective study

BackgroundPatients with recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC) have a poor prognosis and limited therapeutic options. Immune checkpoint inhibitors (ICIs) are effective in patients with tumor progression < 6 months following first-line, platinum-based chemotherapy (PBC), but data are missing for patients with progression ≥ 6 months after the last platinum dose.MethodsRetrospective analysis (six French centers, 2008–2019) of all consecutive R/M-HNSCC patients. treated first-line with PBC and tumor progression ≥ 6 months after the last platinum dose. Primary endpoint: progression-free survival after second-line therapy (PFS2). Additional endpoints: overall survival from Day 1 of first-line (OS1) and second-line (OS2) therapy.ResultsR/M-HNSCC patients (n = 144) received cisplatinum (n = 67, 47%) or carboplatinum (n = 77, 53%) first-line. Response after first-line: complete response (CR; n = 16, 11%); partial response (PR; n = 77, 53%); stable disease (n = 22, 15%). Second-line therapy: PBC (n = 95, 66%); platinum-free regimen (PFR) (n = 25, 17%); ICI (n = 24, 17%). Median [95% confidence interval] PFS (months): PBC 5.0 [3.8–6.2]; PFR 4.0 [1–7.0]; ICI 2.0 [0.4–3.6] (p = 0.16). For PBC, PFR, and ICI, respectively: OS1 30, 23, and 29 months (p = 1.02); OS2 14, 10, and 16 months (p = 0.25); PR, 26%, 16%, and 21% patients; CR, 0%, 8%, and 4% patients. For subsequent lines, ICIs were administered for PBC (n = 11, 12%) and PFR (n = 2, 8%). No predictive factor for efficacy (PFS, OS) was identified.ConclusionsOur retrospective study suggests similar efficacy regarding OS2 for second-line chemotherapy or ICI in R/M-HNSCC patients with progression ≥ 6 months after the last first-line platinum dose.

Effect of voriconazole combined with glucocorticoid on nephrotic syndrome in children.

To explore the efficacy of voriconazole combined with glucocorticoid on the nephrotic syndrome in children. A total of 62 children with nephrotic syndrome were enrolled in this study. They were treated in our hospital from February 2016 to August 2019, including 35 children treated with voriconazole in a control group, and 27 children treated with glucocorticoid combined with voriconazole in a research group. The efficacy was evaluated, and a logistic regression analysis was carried out to find out the risk factors affecting the efficacy. The enzyme-linked immunosorbent assay (ELISA) was used to determine the serum creatinine and urine protein expression before and after treatment. In addition, receiver operating characteristic (ROC) curves were drawn to analyze the predictive value of serum creatinine and urine protein expression. The marked efficacy and total effective rate in the research group were significantly higher than those in the control group, while the non-efficacy in the research group was significantly lower than that in the control group (p<0.05). After treatment, the expression of serum creatinine and urine protein in the research group was significantly lower than that in the control group (p<0.05). The area under the curve (AUC) of urine protein was 0.798. The AUC of serum creatinine was 0.724. Multivariate logistic regression analysis revealed that serum albumin, high edema, infection, serum creatinine, and urine protein were independent risk factors. Glucocorticoid can improve clinical efficacy. Serum creatinine and urine protein can be adopted as predictive factors for efficacy on children with nephrotic syndrome. Serum albumin, high edema, infection, serum creatinine, and urine protein were independent risk factors for the efficacy on children with nephrotic syndrome.

Prognostic factors of cyclosporine A combined with danazol with or without thalidomide in myelodysplastic syndrome treatment with low-percentage bone marrow blasts

目的探讨环孢素A（CsA）联合达那唑±沙利度胺治疗原始细胞不增高骨髓增生异常综合征（MDS）疗效及其影响因素。方法收集2011年12月至2019年12月在中国医学科学院血液病医院确诊且接受CsA联合达那唑±沙利度胺治疗的115例原始细胞不增高初诊原发性MDS患者临床资料，回顾性分析其临床特征、疗效及疗效影响因素，并建立疗效预测模型。结果55例（47.8％）患者获得治疗反应，其中11例获得完全缓解，44例获得血液学改善［红系反应率为49.5％（52/105），血小板反应率为40.7％（35/86），中性粒细胞反应率为35.0％（14/40）］。29例红细胞输注依赖的患者中7例（24.1％）脱离输血依赖。总体中位疗效持续时间为20（3～84）个月。单因素分析显示年龄<60岁较≥60岁患者疗效好（52.5％对22.2％，P＝0.018），而伴红细胞输注依赖较非红细胞输注依赖患者（24.1％对55.8％，P＝0.003）、U2AF1突变型患者较U2AF1野生型患者（26.1％对53.2％，P＝0.020）疗效差。多因素分析显示年龄<60岁（OR＝4.302, 95％CI 1.245～14.820，P＝0.021）、无红细胞输注依赖（OR＝3.774，95％CI 1.400～10.177，P＝0.009）和无U2AF1突变（OR＝3.414，95％CI 1.168～9.978，P＝0.025）均为获得血液学改善的独立预后因素。联合上述影响疗效的独立预后因素建立疗效预测模型，具有0、1、2、3个危险因素患者的总有效率分别为65％、30％～35％、10％～15％、3％。结论CsA联合达那唑±沙利度胺可有效改善原始细胞不增高MDS患者的血细胞减少症状。年龄<60岁、不伴红细胞输注依赖且无U2AF1突变患者治疗反应较好。

Factors influencing efficacy of complete decongestive treatment in patients with breast cancer-linked arm lymphoedema

Background/Aim: The most recommended form of lymphoedema therapy is complete decongestive treatment (CDT). Efficacy of CDT in patients with arm lymphoedema related to malignant breast tumour has reported in many studies, but the predictive factors of outcome of this therapy have not been yet sufficiently investigated. The purpose of this research was to identify predictive factors of efficacy of CDT in patients with breast cancer-linked arm lymphoedema throughout the intensive phase of therapy. Methods: The prospective study included 51 patients with breast cancer-linked arm lymphoedema who were subjected to a 3-week program of CDT. Patients' clinical and demographic features, breast cancer treatment characteristics, lymphoedema and CDT characteristics were collected and assessed for their prognostic value. The influence of certain predictors on the degree of lymphoedema reduction was evaluated by multivariate linear regression analysis. Results: Mean age was 58.1 ± 8.0 (95 % CI: 55.8 - 60.3), median of BMI was 28.4 kg/m2 (95 % CI: 27.2 - 29.6). The average duration of lymphoedema was 36.5 ± 43.9 months (95 % CI: 24.1 - 48.8). The mean size of lymphoedema before CDT was 6.99 ± 5.36 %, and the mean degree of lymphoedema reduction was 63.7 ± 28.6 %. The mean compliance to bandages was 217.5 ± 97.8 hours (95 % CI: 190.0 - 245.0) and 7 (13.7 %) patients had a history of erysipelas of the ipsilateral arm. When observing each individual predictor, statistically most significant contribution showed the size of lymphoedema before the therapy (p &lt; 0.001), then history of erysipelas (p &lt; 0.01), and patients' age (p &lt; 0.05). Conclusion: Size of lymphoedema before treatment is the most crucial prognostic factor of the efficacy of CDT in the patients with breast cancer-linked arm lymphoedema. The present study also identified history of erysipelas and patients age as independent predictors of the CDT efficacy.

The relationship between treatment-induced hypertension and efficacy of anlotinib in recurrent or metastatic esophageal squamous cell carcinoma.

Objective:In this post-hoc analysis, we evaluated anlotinib treatment-induced hypertension as a potential predictive factor of efficacy in esophageal squamous cell carcinoma (ESCC) patients.Methods:A total of 109 patients enrolled in the anlotinib group in a phase 2 trial were included. The tumor response was assessed by computed tomography at week 3, week 6, and then every 6 weeks until progressive disease was observed. The primary endpoint of the study was progression free survival (PFS). The secondary endpoints included overall survival (OS) and objective response rate (ORR).Results:In all patients, the median PFS was 3.02 months [95% confidence interval (CI): 2.63–3.65 months] and the OS was 6.11 months (95% CI: 4.40–7.79 months). The ORR was 7.34% (95% CI: 3.22%–13.95%). A total of 59 (54%) patients were diagnosed with treatment-induced hypertension (Group A), and the remaining patients (n = 50, 46%) were in Group B. Baseline prognostic factors were similar between the 2 groups. Patients in Group A had a longer PFS and OS and higher ORR. When stratifying patients using a previously known history of hypertension, treatment-induced hypertension was a predictor only for patients without previous hypertension, who had longer PFS [hazard ratio (HR): 0.40, 95% CI: 0.24–0.68] and OS (HR: 0.37, 95% CI: 0.21–0.67).Conclusions:We showed, for the first time, a correlation between treatment-induced hypertension and better prognoses in recurrent or metastatic ESCC patients treated with anlotinib, without a previously known history of hypertension. Treatment-induced hypertension may be a simple and low cost predictor for anlotinib antitumor efficacy in these patients, which may also reflect the intended target inhibition.

A prospective, open-label, single-arm study to evaluate the efficacy of dydrogesterone in the treatment of endometrial polyps

Object To evaluate the efficacy of dydrogesterone for the treatment of premenopausal patients with endometrial polyps (EPs). Methods A single-center, open-label, prospective, single-arm clinical treatment trial was conducted in patients of reproductive age with EP(s). Patients were prescribed dydrogesterone from day 15 to day 24 of the menstrual cycle over a period of 3 months. At the 3-month follow-up, the efficacy of dydrogesterone was evaluated based on changes in self-report symptoms and ultrasonographic characteristics. The predictive factors of efficacy as well as the predictive value of the significant factors were also assessed. Results A total of 60 patients were included. Improvements in both symptoms and ultrasound findings occurred in 31 patients, achieving an efficacy rate of 51.67%. Of 41 patients with clinical presentations, 39 (95.1%) reported improvements in symptoms. In terms of ultrasound findings, 33 (55%) of patients demonstrated improvements. Significant decreases were observed in the mean endometrial thickness (1.17 ± 0.33 cm vs 0.90 ± 0.35 cm, p < .001) and polyp size (1.10 ± 0.34 cm vs 0.74 ± 0.65 cm, p = .001) after the application of dydrogesterone. Age (p = .006), polyp size (p = .006), and blood flow within polyps (p = .035) were significant predictors of dydrogesterone efficacy. These factors, when combined, demonstrated a good predictive value ([area under the curve (AUC)=0.81]). Conclusion Dydrogesterone is effective in the management of EPs in premenopausal patients. Age, polyp size and blood flow should be taken into consideration when prescribing dydrogesterone for this population of women.

Abstract 5390: High serum interleukin 6 level associates with early death after initiation of treatment with PD-1 inhibitor in advanced NSCLC

Abstract Anti-PD-1 therapy has been the standard treatment for advanced NSCLC patients. Some patients show durable response, while there are cases that show rapid progression after initiation of ICI treatment, which leads to early death. Therefore, we need a clear biomarker that identifies for early death after initiation of ICI treatment. We reported that CRP is a predictive marker for the efficacy of nivolumab for advanced NSCLC. Among pro-inflammatory cytokines, IL 6 and IL-1β are reported as a poor prognostic factor of cancer patients, and TNFα and INF-γ are reported to be one of the predictors of ICI efficacy.The aim of this study is to investigate the relationship between serum pro-inflammatory cytokines levels and the efficacy of ICI treatment and early death after ICI treatment. Methods: We retrospectively reviewed the predictive factors of efficacy and early death (death within 3 months after initiation of treatment) in anti-PD-1 monotherapy in all cohort (N=307). Based on the results in all cohort, we investigated the relationship of proinflammatory cytokines (IL-1β, IL6, IL10, INFγ) level in serum before pre-anti PD-1 therapy by Luminex® system and the clinical outcome of anti-PD-1 treatment in cytokine cohort (N=67). Patients with advanced or postoperative recurrence NSCLC who received 1≤ dose of ICI from December 2015 to September 2018 in our institute were included. Results: Among 307 patients, 45 patients (14.6%) died within 3 months after the initiation of anti-PD-1 therapy in all cohort. The median PFS of ICI treatment was 3.1months (95%CI: 2.5-4.1). EGFR or ALK mutation, poor PS (2≤), PD-L1 negative, high CRP(1.0 mg/dl≤) were identified as predictive factors for shorter PFS using Cox proportional model. Poor PS, high lung immune prognostic index (2≤), low albumin (&amp;lt;3.5mg/dl), and high CRP were identified in multivariate analysis using the log-rank test for early death. In cytokine cohort, high IL6(4ng/dl≤) and high IL-1β(0.5ng/dl) were identified for shorter PFS ([IL-1β]: 3.0 [1.4-4.5] vs 5.9 [1.8-9.6] months, p=0.016, and [IL6]: 1.9 [1.4-2.6] vs. 4.7 [3.0-7.5] months, p=0.008). High IL6 level was identified for the factors of early death after ICI treatment in multivariate analysis (p=0.001). Although IL1β level had no difference in PS and CRP level, IL6 level significantly increased as PS and CRP increased ([PS] 0 to 1, p=0.004, PS1 to 2, p=0.072, and [IL6]: low CRP 19% vs high CRP 86%, p&amp;lt;0.001) . Conclusions:This analysis demonstrated that serum high IL6 level at baseline associated with the early death after initiation anti-PD-1 treatment and shorter PFS in advanced NSCLC. Citation Format: Yuko Oya, Tatsuya Yoshida, Teppei Yamaguchi, Hiroaki Kuroda, Junichi Shimizu, Yoshitsugu Horio, Hirokazu Matsushita, Toyoaki Hida. High serum interleukin 6 level associates with early death after initiation of treatment with PD-1 inhibitor in advanced NSCLC [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5390.

Ramucirumab, A Second-Line Option For Patients With Hepatocellular Carcinoma: A Review Of The Evidence.

Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and predominantly develops in patients with liver cirrhosis. In patients with advanced disease, such as extra-hepatic extension or portal vein involvement, and with intermediate disease unsuitable for locoregional therapies, systemic therapy is recommended, if liver function and performance status are adequate. Following a decade of negative Phase III trials since the approval of sorafenib, more recently several drugs have proven efficacy both in first line versus sorafenib (lenvatinib) or in second line versus placebo (regorafenib, cabozantinib, ramucirumab). In this review, we summarize the preclinical and clinical evidence supporting the use of ramucirumab, a recombinant IgG1 monoclonal antibody that specifically binds to Vascular Endothelial Growth Factor receptor 2 (VEGFR-2), in HCC. Following the results of the REACH trial, that was negative in the overall study population but identified a subgroup that could benefit from ramucirumab treatment, the REACH-2 trial was a randomized, placebo-controlled trial, designed to assess ramucirumab as second line in patients with alpha-fetoprotein (AFP) ≥400 ng/mL. The results of REACH-2 were published in February 2019, leading to Food and Drug Administration and European Medicines Agency approval of the drug as second-line agent for advanced HCC (after sorafenib) in patients with AFP ≥400 ng/mL. For the first time in the history of systemic treatments for HCC, a predictive factor of efficacy was identified. In this review, we also discuss the potential clinical development of systemic treatments in HCC, focusing on combination therapies with immunotherapy (following the recent results of the combination of atezolizumab and bevacizumab in the IMbrave 150 clinical trial) and treatment sequences as a way to maximize survival benefit.

Leukocyte nadir as a predictive factor for efficacy of adjuvant chemotherapy in breast cancer. Results from the prospective trial SBG 2000–1

Background: Retrospective studies have suggested that chemotherapy-induced leukopenia is associated with improved recurrence-free or overall survival. The SBG 2000–1 trial was designed to verify the favorable prognosis associated with chemotherapy-induced leukopenia in early breast cancer. Patients not experiencing chemotherapy-induced leukopenia were randomized into standard dosed or individually escalated chemotherapy doses based on the grade of leukopenia after a first standard dose.Patients and methods: 1452 women in Sweden and Denmark with operable node-positive or high-risk node-negative breast cancer aged 18–60 years were recruited to participate in this trial. Participants received a first FEC cycle at standard doses (600/60/600 mg/m2). Patients (n = 1052) with nadir leukopenia grade 0–2 after the first cycle were randomized between either 6 standard FEC or 6 tailored FEC courses with doses of epirubicin and cyclophosphamide escalated during courses 2 and 3 and thereafter aimed at achieving grade 3 leukopenia. Patients with nadir leukopenia grade 3–4 after the first course continued treatment with standard FEC. Results of the randomized comparison has been published previously. The present study focuses on chemotherapy-induced leukopenia as a covariable with outcome in randomized and non-randomized patients. The prognostic value of leukopenia after course 3, was studied in a Cox model adjusted for cumulative doses of epirubicin and cyclophosphamide. The association of chemotherapy-induced leukopenia with prognosis was a preplanned secondary endpoint for this trial.Results: The eight-year distant disease-free survival was 73%, 77%, 78% and 83% for patients with leucocyte nadir grade 0, 1, 2 and 3–4, respectively. Higher degree of leukopenia was highly significantly associated to improved distant disease-free survival (HR 0.84, 95% CI 0.74–0.96, p = .008) and overall survival (HR 0.87 (0.76–0.99, p = .032).Conclusion: This prospective study confirms that chemotherapy-induced leukopenia is a covariable with outcome in primary breast cancer, even after adjustment for chemotherapy doses.

Recellularized Colorectal Cancer Patient-derived Scaffolds as in vitro Pre-clinical 3D Model for Drug Screening.

Colorectal cancer (CRC) shows highly ineffective therapeutic management. An urgent unmet need is the random assignment to adjuvant chemotherapy of high-risk stage II and stage III CRC patients without any predictive factor of efficacy. In the field of drug discovery, a critical step is the preclinical evaluation of drug cytotoxicity, efficacy, and efficiency. We proposed a patient-derived 3D preclinical model for drug evaluation that could mimic in vitro the patient’s disease. Surgically resected CRC tissue and adjacent healthy colon mucosa were decellularized by a detergent-enzymatic treatment. Scaffolds were recellularized with HT29 and HCT116 cells. Qualitative and quantitative characterization of matched recellularized samples were evaluated through histology, immunofluorescences, scanning electron microscopy, and DNA amount quantification. A chemosensitivity test was performed using an increasing concentration of 5-fluorouracil (5FU). In vivo studies were carried out using zebrafish (Danio rerio) animal model. Permeability test and drug absorption were also determined. The decellularization protocol allowed the preservation of the original structure and ultrastructure. Five days after recellularization with HT29 and HCT116 cell lines, the 3D CRC model exhibited reduced sensitivity to 5FU treatments compared with conventional 2D cultures. Calculated the half maximal inhibitory concentration (IC50) for HT29 treated with 5FU resulted in 11.5 µM in 3D and 1.3 µM in 2D, and for HCT116, 9.87 µM in 3D and 1.7 µM in 2D. In xenograft experiments, HT29 extravasation was detected after 4 days post-injection, and we obtained a 5FU IC50 fully comparable to that observed in the 3D CRC model. Using confocal microscopy, we demonstrated that the drug diffused through the repopulated 3D CRC scaffolds and co-localized with the cell nuclei. The bioengineered CRC 3D model could be a reliable preclinical patient-specific platform to bridge the gap between in vitro and in vivo drug testing assays and provide effective cancer treatment.

High-intensity focused ultrasound (HIFU) therapy for benign thyroid nodules: a 3-year retrospective multicenter follow-up study

Background Outcomes of high-intensity focused ultrasound (HIFU), as a non-surgical treatment option for benign symptomatic thyroid nodules, has mainly been based on single-center studies and short-term follow-up. Therefore, we assessed the safety, and long-term efficacy of HIFU in benign thyroid nodules among four centers with expertise in thyroid mini-invasive procedures. Patients and methods Retrospective three year follow-up study in four European centers, treating solid benign thyroid nodules causing pressure symptoms and/or cosmetic concerns. Nodule volume reduction was assessed at 1, 3, 6, 12, 24, and 36 months post-treatment. Technical efficacy, defined as a volume reduction rate (VVR) >50% was evaluated at 6, 12, 24 and 36 months. Predictive factors of efficacy were assessed using logistic models. Complications and side effects were classified according to the Interventional Radiology Guidelines and changes in local symptoms were scored on a visual-analog scale. Results Sixty-five patients (mean age 51.1 ± 14.0 years; 86.2% women) with a single thyroid nodule and a mean baseline nodule volume of 9.8 ± 10.3 mL were treated with a mean energy of 7.1 ± 3.1 kJ (range: 2.0 to 15.5 kJ). Median nodule volume reduction was 31.5% (IQR: −38.6% to −23.1%) at 12 months and 31.9% (IQR: −36.4% to −16.1%) at 36 months. Technical efficacy was obtained in 17.2% of cases at 6 months, 17.8% at 12 months, 3.4% at 24 months, and 7.4% at 36 months. The number of treated pixels and the mean energy delivered were positively correlated to VRR at 1, 6 and 12 months. The risk of treatment failure decreased by 4.3% for each additional unit of energy delivered. The procedure duration was inversely correlated with treatment failure (OR 1.043, 95% CI: 1.011–1.083; p = 0.014). Improvement of cervical pressure symptoms or cosmetic complaints were observed in less than 15% of the cases at 12, 24 and 36 months. Horner’s syndrome occurred in one case (1.5%) and minor complications, not requiring treatment, in three (4.6%) patients. No change in thyroid function was registered. Conclusions HIFU carried a low risk of complications. A single treatment resulted in a 30–35% thyroid nodule volume decrease within one year, reduction that remained stable for 2 years. Outcomes varied significantly between centers with different HIFU expertise. Focus on improved HIFU technology, adequate training, and appropriate selection of patients is needed to achieve efficacy comparable to other thermal ablation procedures.

Identifying predictive factors for efficacy in high intensity focused ultrasound (HIFU) ablation of benign thyroid nodules – a retrospective analysis

Objective Since it is unclear whether clinical parameters can independently predict the subsequent treatment response following high intensity focused ultrasound (HIFU) ablation of benign thyroid nodules, we aimed to examine clinical factors that may independently predict 12-month efficacy after HIFU treatment. Methods One hundred and forty patients who had single ablation were categorized into two groups, those with 12-month nodule shrinkage above the median (Group I, n = 70) and with shrinkage below or equal to the median (Group II, n = 70). Baseline characteristics, treatment parameters, percentage change in serum TSH, Free thyroxine (FT4) and thyroglobulin (Tg) from baseline to Day 4 and appearance of microbubbles (hyperechoic marks (HEMs)) during treatment were compared between groups. To determine independent factors, a multivariate analysis was done by logistic regression analysis. Results Baseline characteristics and treatment parameters were comparable between groups. However, on Day-4, group I had significantly lower serum TSH (0.49mIU/L vs. 0.84mIU/L, p = 0.011) and higher FT4 (22.11 pmol/L vs. 18.47 pmol/L, p = 0.008) than group II. The percentage change in TSH, FT4 and Tg were significantly greater in group I (p = 0.002, p = 0.009 and p = 0.001 respectively). The proportion of HEMs observed during treatment was also significantly higher in group I (42.69% vs. 31.72%, p = 0.030). Among the significant factors, the percentage change in FT4 was the only independent factor for 12-month shrinkage (OR = 1.018, 95%CI =1.003–1.032, p = 0.017). Conclusions Percentage change in serum FT4 on post-treatment Day-4 was an independent blood parameter for the subsequent nodule shrinkage at 12 months. This finding could potentially facilitate the decision for earlier retreatment of treated nodules.

585P - POLAF study: Efficacy and safety of FOLFIRI/aflibercept in a phase II trial in patients with metastatic colorectal cancer: Results of plasmatic prognostic and predictive markers

BackgroundBiomarkers associated to antiangiogiogenic agents in metastatic colorectal cancer (mCRC) have not yet been validated Here we present the efficacy and safety results of FOLFIRI and aflibercept in second line therapy for mCRC and the analysis of biomarkers as predictive factors of efficacy. MethodsPOLAF is a multicenter, non comparative, phase II study conducted in patients with mCRC previously treated with oxaliplatin (NCT02970916) Plasma biomarkers were assayed using ELISA Vascular endothelial growth factor (VEGF A) and angiotensin-converting enzyme (ACE) biomarkers were statistically analyzed (Roc Curve) with respect to the primary endpoint (PE): progression free survival (PFS) (Kaplan Meier). ResultsBetween November 2016 and December 2017, 101 patients for the PE were enrolled: male 59.4%, median age of 63.8 years and ECOG 0 in 46.5% of them The median of treatment duration was 5.7 months. Later antitumor therapies were received by 54.5% pts With a median follow up of 11.7 months, response rates were: PR 15.8%, SD 53.5% and PD 25.7%. The median OS, PFS, TTP and to TTF were 12.6, 7.4, 8.3 and 6.1 months, respectively Of note, both OS and PFS were significantly longer in pts with lower plasma VEGF A levels (<1.941ng/ml) in comparison to those with higher levels (p<0.001) No significant differences were detected in plasma ACE levels (Table) A total of 74.3% pts presented at least 1 grade ≥ 3 toxicity, being the most common asthenia (24.8%) hypertension (22.8%) and neutropenia (23.9%) and three pts presented grade 5 toxicity: one hepatic encephalopathy, one gastrointestinal toxicity and one unknown reason that treatment relationship could not be ruled out.Table585PTableCut offaPFSOSVEFG-A<1.9419.2 (8.4-10)18.9 (14.8-23)≥1.9414.2 (2.7-5.6)7.6 (4.5-10.7)p<0.001ACE<1358.8 (7.4-10.3)15.2 (9.4-21.1)≥1356.8 (3.7-10)11.7 (9.0-14.5)p=0.103p=0.889aOptimal point that maximizes sensitivity and specifity (ng/ml). ConclusionsThis study confirms the efficacy outcomes of FOLFIRI/aflibercept regimen in second line mCRC Our data shows that VEGF-A could be related to the survival of this population and its role as a potential predictive biomarker for efficacy should be considered. Legal entity responsible for the studyThe authors. FundingSanofi. DisclosureM.E. Elez Fernandez: Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Merck; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Sanofi; Honoraria (self), Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen; Honoraria (institution), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Honoraria (self): Servier; Honoraria (self), Honoraria (institution): Array; Honoraria (institution): Novartis; Honoraria (institution): Boehringer Ingelheim; Honoraria (institution): MSD; Honoraria (institution): Servier; Honoraria (institution): Bayer; Honoraria (institution): GSK; Honoraria (institution): Pharmamar. B. Graña Suarez: Research grant / Funding (self): Sanofi; Research grant / Funding (self): Gilead; Research grant / Funding (self): Amgen. M. Valladares-Ayerbes: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AMGEN; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Servier; Honoraria (self), Speaker Bureau / Expert testimony: Bayer; Honoraria (self): BRISTOL; Advisory / Consultancy: Sanofi. M. Salgado Fernandez: Travel / Accommodation / Expenses: Sanofi. E. Martínez de Castro: Speaker Bureau / Expert testimony: Sanofi. A. Ruiz-Casado: Honoraria (self), Research grant / Funding (self): Sanofi; Honoraria (self): Amgen; Honoraria (self): Merck; Honoraria (self): Lilly; Honoraria (self): Servier; Honoraria (self): Roche; Honoraria (self): Medtronic; Honoraria (self): BTG; Honoraria (self): Bayer. E. Aranda Aguilar: Advisory / Consultancy: Amgen; Advisory / Consultancy: Bayer; Advisory / Consultancy: Celgene; Advisory / Consultancy: Merck Advisory / Consultancy: Roche; Advisory / Consultancy: Sanofi. All other authors have declared no conflicts of interest.

Impact of genotype in relapsed and refractory acute myeloid leukaemia patients treated with clofarabine and cytarabine: a retrospective study

The treatment of relapsed/refractory (R/R) acute myeloid leukaemia (AML) remains a challenge. Among salvage chemotherapy regimens, the clofarabine and cytarabine (CLARA) combination has been widely evaluated and has a favourable safety/efficacy balance. Predictive factors of efficacy in patients with R/R AML are unclear, particularly the impact of AML-related gene mutations. We report our single-centre experience on 34 R/R AML patients treated with CLARA, with a focus on the genetic characterization of our cohort. CLARA yielded a 47% response rate among this poor-prognosis AML population, while two patients (5·8%) died due to treatment-related toxicity. The two-year progression-free survival and overall survival rates were 29·4% and 35·3%, respectively. Nine patients (26%) had long-term response with a median follow-up of 39·5months among the responders, of whom six underwent haematopoietic stem cell transplantation. Adverse karyotype did not correlate with response or survival, and secondary AML were more frequent among responders to CLARA, suggesting that this combination may successfully salvage R/R AML patients regardless of adverse prognostic markers. We also observed that a low mutational burden and absence of splice mutations correlated with prolonged survival after CLARA, suggesting that extensive genotyping may have prognostic implications in R/R AML.

Impact of baseline number of metastases on the efficacy of PD-1 inhibitor monotherapy for non-small cell lung cancer with high PD-L1 expression.

e20551 Background: Pembrolizumab monotherapy and pembrolizumab combined with platinum-based chemotherapy are the standard therapies for advanced non-small cell lung cancer (NSCLC) patients with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) ≥ 50%. Apart from PD-L1 status, predictive factors for the efficacy of pembrolizumab treatment remain unclear. High tumour burden has been shown to be a negative predictor for the efficacy of PD-1 inhibitors in melanoma. Hence, the purpose of this study was to evaluate the association between tumour burden and efficacy of pembrolizumab in NSCLC patients with PD-L1 TPS ≥ 50%. Methods: This single-center retrospective observational study evaluated patients with advanced NSCLC with PD-L1 TPS ≥ 50% who received pembrolizumab monotherapy as first line therapy between March 2016 and November 2018. The primary endpoint was progression-free survival (PFS). Tumour burden was estimated by the baseline number of metastases (BNM) and the baseline sum of the target lesions’ longest diameters (BSLD; measured according to RECIST criteria). Results: Of 52 patients with target lesions, the median age was 69 years; ECOG-PS 0-1 94%; non-squamous histology 79%; and PD-L1 TPS ≥ 75% was 65%. The optimal cut-off values for predicting PFS were 4 for BNM and 115 mm for BSLD, based on the minimum P-value method for PFS. The low BNM group included 20 (38%) patients, and the low BSLD group 33 (63%). Low BNM was significantly associated with longer PFS (median PFS not reached vs 4.0 months, HR = 0.35, P = 0.021) and with higher response rate (60% vs 31%, P = 0.041) compared to high BNM. There was no significant difference in PFS between low BSLD and high BSLD groups (12.4 vs 4.0 months, HR = 0.52, P = 0.098). Multivariate analysis showed that both low BNM (≤ 4 vs. &gt; 4, HR = 0.32, P = 0.02) and PD-L1 TPS (75-100% vs. 50-74%, HR = 0.41, P = 0.032) were significantly associated with longer PFS. There was no association between PD-L1 TPS and BNM (Spearman’s rho = -0.0985, P = 0.487) Conclusions: BNM may be an independent predictive factor of efficacy of pembrolizumab monotherapy. Patients with low BNM can be candidates for pembrolizumab monotherapy.

Prolactinomas in women: clinical, neuroradiological and pathological predictive factors for efficacy of transphenoidal surgery

Prolactinomas in women: clinical, neuroradiological and pathological predictive factors for efficacy of transphenoidal surgery