Spanish Head & Neck Cancer Cooperative Group

Patient registries better reflect real-world management and outcomes of pancreatic cancer (PC) compared with clinical trials. The main objective was to characterize patterns of care and outcomes in patients with exocrine PC included in the Spanish gastrointestinal RETUD registry. All analyses are descriptive in nature; therefore, P values are not reported. A total of 1438 patients with a median age of 68.7 years (range: 34-94 years) were included between 1 January 2019 and 31 December 2022. 79.7% of patients had an Eastern Cooperative Oncology Group performance status of 0-1. 54.9% of resectable patients received adjuvant chemotherapy after upfront surgery, with a median overall survival (mOS) of 33.3 months (range: 26.1 months-not reached) for those treated with Folfirinox. 79.5% of metastatic patients received first-line chemotherapy, primarily gemcitabine and nab-paclitaxel (62.6%), with a mOS of 8.7 months (range: 7.1-9.6 months). Overall, 1- and 3-year net survival rates were 46% and 9%, respectively, with a clear increase for resectable/borderline stages. KRAS, microsatellite instability (MSI), and germline BRCA1/2 were determined in 16.4% (81.8% mutated), 21.2% (1.6% MSI-high), and 9.2% (12.8% mutated) of patients, respectively. Our study provides a real-world perspective on PC patients in Spain, revealing very poor survival similar to those reported in population-based and epidemiological studies. Notably, resectable PC patients receiving adjuvant chemotherapy had lower survival compared with those in clinical trials, a trend not observed in more advanced stages. Adherence to international guidelines varied, and clinical trial participation was low. Additionally, access to molecular testing was limited, remaining a significant challenge.

615 Background: Antagonism of Mouse double minute 2 homolog ( MDM2 ) can restore p53 activity and represents a novel therapeutic strategy in biliary tract cancer (BTC). We aimed to characterize the epidemiology of total population versus that harbouring MDM2 amplifications; potential associations of MDM2 to other genetic alterations and survival outcomes. Methods: We evaluated a large real-world cohort of patients (pt) diagnosed with BTC from 1st January 2017 to 31st December 2022 from the Spanish RETUD registry. Next generation sequencing (NGS) test was performed in all patients. Data collected included demographic and clinical characteristics, molecular profile, systemic oncologic treatment and effectiveness (best response and survival outcomes). Progression free survival (PFS) outcomes and best response were calculated for pts who received first line therapy. Descriptive statistic was used to analyse sociodemographic data, tumor characterization, molecular analysis, and best response. PFS and overall survival (OS) were estimated by the Kaplan-Meier method. Results: A total of 301 evaluable pt were included in 24 sites. MDM2 amplifications were reported in 19 pt (6.3%) and 2 pt (10.5%) had TP53 mutations. At primary diagnosis, in the MDM2 amplified population the tumour was mostly intrahepatic (63.2%); followed by gallbladder cancer (21.0%). Half of the pt had advanced disease at diagnosis (52.6%) and 21.0% resectable disease. No significant differences were observed in clinical characteristics (age, sex, tumor location, stage, ECOG performance status and metastasis location) and most common actionable genomic alterations (BRAF, HER2, IDH, FGFR2) in pt with MDM2 amplification compared to overall population. Median overall survival (95% Confidence Interval [CI]) in pt with MDM2 amplification was 18.4 months (12.3-19.9), and 17.8 months (95% CI, 12.3-19.9, p=0.247 in pt without amplification. Median PFS in first-line was 5.3 months (95% CI, 2.7-8.9) in MDM2 amplified group, as compared with 6.0 months in non- MDM2 amplified group (95% CI, 5.3-6.8; p=0.4233. The objective response rate in first-line was 21.4% in the MDM2 amplified group versus 29.6% in non-amplified group. The proportion of pt who received systemic therapy in first, second and third line was similar in both groups. The main first-line regimen in MDM2 amplified pt was cisplatin/gemcitabine (n=9, 47.4%), followed by clinical trial (n=3, 15.8%), GEMOX (n=2, 10.5%) and gemcitabine (n=2, 10.5%). The median OS and PFS of patients treated with cisplatin/gemcitabine in first line was similar in both groups. Conclusions: This analysis provides insights into the characterization of MDM2 amplified BTC pt. Similar incidence of MDM2 amplification was observed compared to other cohorts of BTC. No significant differences were observed in clinical characteristics, molecular profile and survival in MDM2 amplified pt compared to non-amplified pt.

Conflicto de intereses: la autora declara no tener conflictos de interés. Inteligencia artificial: el autor declara no haber usado inteligencia artificial (IA) ni ninguna herramienta que use IA para la redacción del artículo.

In this article the funder name in the Funding information section was incorrectly given as 'Merck' and should have read 'Merck, S.L.U., Spain, an affiliate of Merck KGaA,

The aim of this study was to confirm the efficacy of the ERBITAX scheme (paclitaxel 80 mg/m2 weekly and cetuximab 400 mg/m2 loading dose, and then 250 mg/m2 weekly) as first-line treatment for patients with recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) who are medically unfit for cisplatin-based (PT) chemotherapy. This retrospective, non-interventional study involved 16 centers in Spain. Inclusion criteria were to have started receiving ERBITAX regimen from January 2012 to December 2018; histologically confirmed SCCHN including oral cavity, oropharynx, hypopharynx, and larynx; age ≥18 years; and platinum (PT) chemotherapy ineligibility due to performance status, comorbidities, high accumulated dose of PT, or PT refractoriness. A total of 531 patients from 16 hospitals in Spain were enrolled. The median age was 66 years, 82.7% were male, and 83.5% were current/former smokers. Patients were ineligible to receive PT due to ECOG 2 (50.3%), comorbidities (32%), PT cumulative dose ≥ 225 mg/m2 (10.5%), or PT refractoriness (7.2%). Response rate was 37.7%. Median duration of response was 5.6 months (95% CI: 4.4-6.6). With a median follow-up of 8.7 months (95% CI: 7.7-10.2), median PFS and OS were 4.5 months (95% CI: 3.9-5.0) and 8.9 months (95% CI: 7.8-10.3), respectively. Patients treated with immunotherapy after ERBITAX had better OS with a median of 29.8 months compared to 13.8 months for those who received other treatments. The most common grade ≥ 3 toxicities were acne-like rash in 36 patients (6.8%) and oral mucositis in 8 patients (1.5%). Five (0.9%) patients experienced grade ≥ 3 febrile neutropenia. This study confirms the real-world efficacy and tolerability of ERBITAX as first-line treatment in recurrent/metastatic SCCHN when PT is not feasible. Immunotherapy after treatment with ERBITAX showed remarkable promising survival, despite potential selection bias.

Purpose:Follicular lymphoma (FL) is the most frequent indolent non-Hodgkin lymphoma. Around 20% of patients suffer early disease progression within 24 months (POD24) of diagnosis. This study examined the significance of circulating tumor DNA (ctDNA) in predicting response to therapy and POD24 in patients with FL.Experimental Design:We collected 100 plasma samples, before and during the treatment, from 36 patients with FL prospectively enrolled in 8 Spanish hospitals. They were treated with a chemotherapy-rituximab regimen and followed up for a median of 3.43 years. We performed targeted deep sequencing in cell-free DNA (cfDNA) and tumor genomic DNA from 31 diagnostic biopsy samples.Results:Of the alterations detected in the diagnostic tissue samples, 73% (300/411) were also identified in basal cfDNA. The mean numbers of alterations per basal cfDNA sample in patients who suffered progression of disease within 24 months (POD24-pos) or did not achieve complete response (non-CR) were significantly higher than in POD24-neg or CR patients (unpaired samples t test, P = 0.0001 and 0.001, respectively). Pretreatment ctDNA levels, as haploid genome equivalents per milliliter of plasma, were higher in patients without CR (P = 0.02) and in POD24-pos patients compared with POD24-neg patients (P < 0.001). Dynamic analysis showed that ctDNA levels decreased dramatically after treatment, although the reduction was more significant in patients with CR and POD24-neg patients.Conclusions:Basal ctDNA levels are associated with the risk of early progression and response to treatment in FL. cfDNA monitoring and genotyping during treatment and follow-up predict response to treatment and early progression.