Prediction of progression-free survival in patients with advanced, well-differentiated, neuroendocrine tumors being treated with a somatostatin analog: the GETNE-TRASGU study

Artículo escrito por un elevado número de autores, sólo se referencian el que aparece en primer lugar, y los autores pertenecientes a la UAMSomatostatin analogs (SSAs) are recommended for the first-line treatment of most patients with well-differentiated, gastroenteropancreatic (GEP) neuroendocrine tumors; however, benefit from treatment is heterogeneous. The aim of the current study was to develop and validate a progression-free survival (PFS) prediction model in SSA-treated patients. PATIENTS AND METHODS We extracted data from the Spanish Group of Neuroendocrine and Endocrine Tumors Registry (R-GETNE). Patient eligibility criteria included GEP primary, Ki-67 of 20% or less, and first-line SSA monotherapy for advanced disease. An accelerated failure time model was developed to predict PFS, which was represented as a nomogram and an online calculator. The nomogram was externally validated in an independent series of consecutive eligible patients (The Christie NHS Foundation Trust, Manchester, United Kingdom). RESULTS We recruited 535 patients (R-GETNE, n = 438; Manchester, n = 97). Median PFS and overall survival in the derivation cohort were 28.7 (95% CI, 23.8 to 31.1) and 85.9 months (95% CI, 71.5 to 96.7 months), respectively. Nine covariates significantly associated with PFS were primary tumor location, Ki-67 percentage, neutrophil-to-lymphocyte ratio, alkaline phosphatase, extent of liver involvement, presence of bone and peritoneal metastases, documented progression status, and the presence of symptoms when initiating SSA. The GETNE-TRASGU (Treated With Analog of Somatostatin in Gastroenteropancreatic and Unknown Primary NETs) model demonstrated suitable calibration, as well as fair discrimination ability with a C-index value of 0.714 (95% CI, 0.680 to 0.747) and 0.732 (95% CI, 0.658 to 0.806) in the derivation and validation series, respectively. CONCLUSION The GETNE-TRASGU evidence-based prognostic tool stratifies patients with GEP neuroendocrine tumors receiving SSA treatment according to their estimated PFS. This nomogram may be useful when stratifying patients with neuroendocrine tumors in future trials. Furthermore, it could be a valuable tool for making treatment decisions in daily clinical practiceFunded by a restricted grant from Novartis Farmacéutic

Why Young patients with cancer requiere different coping tools?

The medical field has made great advancements in recent decades, but even one in every two men and one in three women will suffer from cancer throughout their lives [1]. Furthermore, cancer was the leading cause of death due to illness in the adolescent and young adult (18-39 year old) population [2]. Despite these figures, no one thinks he is close to suffering from cancer. We prefer to think that it is a disease related to some other collective that we perceive as distant. We are not prepared to deal with the processes involved in the diagnosis and treatment of cancer. Therefore, it is a disease that poses challenges beyond the medicine itself and that forces to take action in relation to the personal and social environment of the patient, measures that will probably transform their present and future lifestyle. This becomes especially relevant if we focus on cancer in young patients [3]

Living with cancer: throught the eyes of the patient and the physician

This article is co-authored by a patient with colon cancer and his treating oncologist, who interact at two different levels: the instrumental and the emotional and affective one. The patient relates in detail his personal experiences struggling with cancer, including his fears, expectations, purposes, and attitudes through the most important events in the evolution of his illness. The professional reflects how patient-based communication and shared decision-making impact on quality of life and coping with cancer

External validity of clinical trials with diverse trastuzumab-based chemotherapy regimens in advanced gastroesophageal adenocarcinoma: data from the AGAMENON-SEOM registry

Quimioteràpia; Càncer gàstric; TrastuzumabQuimioterapia; Cáncer gástrico; TrastuzumabChemotherapy; Gastric cancer; TrastuzumabBackground: Trastuzumab combined with cisplatin and fluoropyrimidines, either capecitabine or 5-fluorouracile (XP/FP), is the standard first-line treatment for advanced, HER2-positive, gastric cancer patients based on the ToGA trial. Despite the lack of phase III trials, many clinicians administer trastuzumab with alternative regimens. One meta-analysis suggests that substituting cisplatin for oxaliplatin might lead to greater efficacy and less toxicity. Methods: 594 patients with HER2-positive gastroesophageal adenocarcinoma were recruited from the AGAMENON-SEOM registry. The objective was to evaluate the external validity of clinical trials with chemotherapy and trastuzumab. Results: The regimens used in at least 5% of the patients were XP (27%), oxaliplatin and capecitabine (CAPOX) (26%), oxaliplatin and 5-fluorouracil (FOLFOX) (14%), FP (14%), triplet with anthracycline/docetaxel (7%), and carboplatin-FU (5%). Median exposure to trastuzumab was longer with FOLFOX (11.4 months, 95% CI, 9.1–21.0) versus ToGA regimens (7.5, 6.4–8.5), p < 0.001. Patients with HER2-IHC 3+ cancers had higher response rates than those with IHC 2+/FISH+, odds-ratio 1.97 (95% CI, 1.25–3.09). The results achieved with CAPOX–trastuzumab were comparable to those attained with ToGA regimens. FOLFOX–trastuzumab was superior to ToGA schemes in terms of overall survival (OS), with a greater magnitude of effect in IHC 2+/FISH+ tumors (HR 0.47, 0.24–0.92) compared with IHC 3+ (HR 0.69, 0.49–0.96), and in diffuse (HR 0.37, 0.20–0.69) versus intestinal-type tumors (HR 0.76, 0.54–1.06). Conclusion: We have updated the external validity of clinical trials with trastuzumab in first-line treatment of gastric cancer. Our data confirm the comparable outcomes of ToGA regimens and CAPOX–trastuzumab in clinical practice and point toward a possible benefit of FOLFOX–trastuzumab, contingent on the subtypes typically less sensitive to trastuzumab, to be confirmed in clinical trials.The authors received no financial support for the research, authorship, and/or publication of this article

SEOM-GETNE clinical guidelines for the diagnosis and treatment of gastroenteropancreatic and bronchial neuroendocrine neoplasms (NENs) (2022)

Diagnosis; Neuroendocrine; TherapyDiagnòstic; Neuroendocrí; TeràpiaDiagnóstico; Neuroendocrino; TerapiaNeuroendocrine neoplasms (NENs) are a heterogeneous family of tumors of challenging diagnosis and clinical management. Their incidence and prevalence continue to rise mainly due to an improvement on diagnostic techniques and awareness. Earlier detection, along with steadfast improvements in therapy, has led to better prognosis over time for advanced gastrointestinal and pancreatic neuroendocrine tumors. The aim of this guideline is to update evidence-based recommendations for the diagnosis and treatment of gastroenteropancreatic and lung NENs. Diagnostic procedures, histological classification, and therapeutic options, including surgery, liver-directed therapy, peptide receptor radionuclide therapy, and systemic hormonal, cytotoxic or targeted therapy, are reviewed and discussed, and treatment algorithms to guide therapeutic decisions are provided

The AGAMENON-SEOM model for prediction of survival in patients with advanced HER2-positive oesophagogastric adenocarcinoma receiving first-line trastuzumab-based therapy

Gastric cancer; Survival; TrastuzumabCàncer gàstric; Supervivència; TrastuzumabCáncer gástrico; Supervivencia; TrastuzumabBackground: Trastuzumab and chemotherapy is the standard first-line treatment in human epidermal growth factor receptor 2 (HER2)-positive advanced gastro-oesophageal cancer. The objective was to develop a predictive model for overall survival (OS) and progression-free survival (PFS) in patients treated with trastuzumab. Methods: Patients with HER2-positive advanced gastro-oesophageal adenocarcinoma (AGA) from the Spanish Society of Medical Oncology (SEOM)-AGAMENON registry and treated first line with trastuzumab and chemotherapy between 2008 and 2021 were included. The model was externally validated in an independent series (The Christie NHS Foundation Trust, Manchester, UK). Results: In all, 737 patients were recruited (AGAMENON-SEOM, n = 654; Manchester, n = 83). Median PFS and OS in the training cohort were 7.76 [95% confidence interval (CI), 7.13–8.25] and 14.0 months (95% CI, 13.0–14.9), respectively. Six covariates were significantly associated with OS: neutrophil-to-lymphocyte ratio, Eastern Cooperative Oncology Group performance status, Lauren subtype, HER2 expression, histological grade and tumour burden. The AGAMENON-HER2 model demonstrated adequate calibration and fair discriminatory ability with a c-index for corrected PFS/OS of 0.606 (95% CI, 0.578–0.636) and 0.623 (95% CI, 0.594–0.655), respectively. In the validation cohort, the model is well calibrated, with a c-index of 0.650 and 0.683 for PFS and OS, respectively. Conclusion: The AGAMENON-HER2 prognostic tool stratifies HER2-positive AGA patients receiving trastuzumab and chemotherapy according to their estimated survival endpoints

External validity of docetaxel triplet trials in advanced gastric cancer: are there patients who still benefit?

Bayesian model; Docetaxel; Gastric cancerModel bayesià; Docetaxel; Càncer gàstricModelo bayesiano; Docetaxel; Cáncer gástricoBackground The purpose of our study was to develop an online calculator to estimate the effect of docetaxel triplets (DPF) in first line of advanced gastric cancer (AGC), and to assess the external validity of docetaxel trials in individual patients. Methods The study includes patients with HER2(-) AGC treated with platin and fluoropyrimidine (PF) or with DPF in first line. Treatment effect and interactions were assessed using Bayesian accelerated failure time models. Result The series comprises 1376 patients; 238 treated with DPF and 1138 with PF between 2008 and 2019. DPF was associated with increased progression-free survival (PFS) and overall survival (OS) with time ratio (TR) 1.27 (95% credible interval [CrI], 1.15–1.40), and TR 1.19 (95% CrI, 1.09–1.27), respectively. Serious adverse events were more common with DPF, particularly hematological effects (32% vs 22%). Younger participants received greater DPF dose density without achieving greater disease control, while severe toxicity was likewise higher. DPF yielded superior OS in Lauren intestinal (TR 1.27, 95% CrI, 1.08–1.11) vs diffuse subtype (TR 1.17, 95% CrI, 1.09–1.24) and the probability of increasing OS > 15% was 90% vs 67% in each subtype, respectively. The effect dwindles over time, which can be attributed to pathological changes and clinical practice changes. Conclusion Our study confirms the effect of DPF is highly dependent on several clinical–pathological variables, with discreet and gradually declining benefit over platinum doublets in later years, at the expense of increased toxicity. These results may help to underpin the idea that external validity of AGC trials should be revised regularly

Incidence of sleep problems and their mediating role on depression and anxious preoccupation in patients with resected, non-advanced cancer: data from NEOcoping study

Background: Our study analyzes the incidence of sleep problems and their mediating role on depression and anxious preoccupation in patients with resected, non-advanced cancer. Methods: A multi-institutional, prospective, observational study was conducted with 750 participants of 14 hospitals in Spain. Participants' socio-demographic and clinical characteristics were collected using a standardized self-report form and using EORTC QoL-QLQ-C30, BSI, Mini-MAC questionnaires. Results: In women, sleep problems, depression and anxious preoccupation were observed in 65, 41 and 21%, respectively. In men, sleep problems, depression and anxious preoccupation were reported in 51, 29 and 61%, respectively. More sleep problems, depression and anxious preoccupation were found among women than males. Depression was a significant predictor of anxious preoccupation. In males, sleep problems partially mediated this association. This was not confirmed in women

Intensive care in cancer patients in the age of immunotherapy and molecular therapies: SEOM-SEMICYUC’s commitment.

Cancer patients comprise a vulnerable collective exposed to numerous, serious risks, beyond the cancer itself. In recent years, these individuals’ prognosis has improved substantially thanks to several advances, such as immunotherapy, targeted molecular therapies, surgical techniques, or developments in support treatment. This coincides with the prolonged survival of oncological patients hospitalized in the ICU for critical complications. Thus, the time has come to revisit intensive care support for these patients, which poses new professional as well as organizational challenges. An agreement was therefore signed in 2017 between SEOM and SEMICYUC with the aim of improving the quality of care of cancer patients with critical complications. It seeks to aid in decision-making, standardize criteria, decrease subjectivity, generate channels of communication, and delve deeper into the ethical and scientific aspects of these situations. This document sets forth the most important reasons that have led us to undertake this initiative.pre-print653 K

Position Statement on the Diagnosis, Treatment, and Response Evaluation to Systemic Therapies of Advanced Neuroendocrine Tumors, With a Special Focus on Radioligand Therapy

Neoadjuvant therapy; Peptide receptor radionuclide therapy; ProgressionTeràpia neoadjuvant; Teràpia amb radionúclids del receptor de pèptids; ProgressióTerapia neoadyuvante; Terapia con radionúclidos del receptor de péptidos; ProgresiónBackground The aim of this study was to provide a guidance for the management of neuroendocrine tumors (NETs) in clinical practice. Material and Methods Nominal group and Delphi techniques were used. A steering committee of 8 experts reviewed the current management of NETs, identified controversies and gaps, critically analyzed the available evidence, and formulated several guiding statements for clinicians. Subsequently, a panel of 26 experts, was selected to test agreement with the statements through 2 Delphi rounds. Items were scored on a 4-point Likert scale from 1 = totally agree to 4 = totally disagree. The agreement was considered if ≥75% of answers pertained to Categories 1 and 2 (consensus with the agreement) or Categories 3 and 4 (consensus with the disagreement). Results Overall, 132 statements were proposed, which incorporated the following areas: (1) overarching principles; (2) progression and treatment response criteria; (3) advanced gastro-enteric NETs; (4) advanced pancreatic NETs; (5) advanced NETs in other locations; (6) re-treatment with radioligand therapy (RLT); (7) neoadjuvant therapy. After 2 Delphi rounds, only 4 statements lacked a clear consensus. RLT was not only recommended in the sequencing of different NETs but also as neoadjuvant treatment, while several indications for retreatment with RLT were also established. Conclusion This document sought to pull together the experts’ attitudes when dealing with different clinical scenarios of patients suffering from NETs, with RLT having a specific role where evidence-based data are limited.This project was funded by Advanced Accelerator Applications, a Novartis company