Is short-course radiotherapy and total neoadjuvant therapy the new standard of care in locally advanced rectal cancer? A sensitivity analysis of the RAPIDO clinical trial.

BACKGROUND: The results of the RAPIDO trial have been accepted as evidence in favour of short-course radiotherapy (SC-RT) followed by chemotherapy before total mesorectal excision in high-risk locally advanced rectal cancer. A noteworthy concern is that the RAPIDO trial did not ensure that all patients in the control arm received adjuvant chemotherapy. This may bias statistical estimates in favour of the experimental arm if adjuvant chemotherapy is active in rectal cancer. Moreover, the 5-year update revealed an increase in the risk of local relapse in the experimental arm. MATERIALS AND METHODS: We carried out sensitivity analyses to determine how plausible effects of adjuvant chemotherapy, adjusted by the proportion of patients in the standard arm receiving adjuvant treatment, would have influenced the observed treatment effect estimate of the RAPIDO trial. The most plausible values for the benefit of adjuvant chemotherapy were determined by Bayesian re-analysis of a prior meta-analysis. RESULTS: The meta-analysis suggested that oxaliplatin/fluorouracil-based adjuvant chemotherapy may improve disease-free survival (DFS) in rectal cancer although the signal is weak [hazard ratio (HR) 0.84, 95% credible interval, 0.57-1.15]; probability of benefit (HR <1) was 91.2%. In the sensitivity analysis, the HR for disease-related treatment failure would remain <1, thus favouring total neoadjuvant therapy (TNT), on most occasions, but the null hypothesis would not have been rejected in various credible settings. For the RAPIDO data to be consistent with the null effect, a moderate benefit of adjuvant chemotherapy (HR for DFS between 0.75 and 0.80) and 70%-80% of exposed participants would suffice. CONCLUSION: The decision to make adjuvant chemotherapy optional in the standard arm may have biased the results in favour of the experimental arm, in a scenario in which TNT does not offset the increase in local recurrences after SC-RT.

Anthracycline-based triplets do not improve the efficacy of platinum-fluoropyrimidine doublets in first-line treatment of advanced gastric cancer: real-world data from the AGAMEMON National Cancer Registry.

BACKGROUND: Although anthracycline-based triplets are one of the most widely used schedules to treat advanced gastric cancer (AGC), the benefit of including epirubicin in these therapeutic combinations remains unknown. This study aims to evaluate both the efficacy and tolerance of triplets with epirubicin vs. doublets with platinum-fluoropyrimidine in a national AGC registry. METHODS: Patients with AGC treated with polychemotherapy without trastuzumab at 28 hospitals in Spain between 2008 and 2016 were included. The effect of anthracycline-based triplets against doublets was evaluated by propensity score matching (PSM) and Cox proportional hazards (PH) regression. RESULT: A total of 1002 patients were included (doublets, n = 653; anthracycline-based triplets, n = 349). The multivariable Cox PH regression failed to detect significantly increased OS in favor of triplets with anthracyclines: HR 0.90 (95% CI, 0.78-1.05), p = 0.20035. After PSM, the sample contained 325 pairs with similar baseline characteristics. This method was also unable to reveal an increase in OS: 10.5 (95% CI, 9.7-12.3) vs. 9.9 (95% CI, 9.2-11.4) months, HR 0.91 (CI 95%, 0.76-1.083), and (log-rank test, p = 0.226). Response rates (42.1 vs. 33.1%, p = 0.12) and PFS (HR 0.95, CI 95%, 0.80-1.13, log-rank test, p = 0.873) were not significantly higher with epirubicin-based regimens. The triplets were associated with greater grade 3-4 hematological toxicity, and increased hospitalization due to toxicity by 68%. The addition of epirubicin is viable, but 23.7% discontinued treatment because of adverse effects or patient decision. CONCLUSION: Anthracyclines added to platinum-fluoropyrimidine doublets did not improve the response rate or survival outcomes in patients with AGC but entailed greater toxicity.

Predicting serious complications in patients with cancer and pulmonary embolism using decision tree modelling: the EPIPHANY Index.

BACKGROUND: Our objective was to develop a prognostic stratification tool that enables patients with cancer and pulmonary embolism (PE), whether incidental or symptomatic, to be classified according to the risk of serious complications within 15 days. METHODS: The sample comprised cases from a national registry of pulmonary thromboembolism in patients with cancer (1075 patients from 14 Spanish centres). Diagnosis was incidental in 53.5% of the events in this registry. The Exhaustive CHAID analysis was applied with 10-fold cross-validation to predict development of serious complications following PE diagnosis. RESULTS: About 208 patients (19.3%, 95% confidence interval (CI), 17.1-21.8%) developed a serious complication after PE diagnosis. The 15-day mortality rate was 10.1%, (95% CI, 8.4-12.1%). The decision tree detected six explanatory covariates: Hestia-like clinical decision rule (any risk criterion present vs none), Eastern Cooperative Group performance scale (ECOG-PS; <2 vs ⩾2), O2 saturation (<90 vs ⩾90%), presence of PE-specific symptoms, tumour response (progression, unknown, or not evaluated vs others), and primary tumour resection. Three risk classes were created (low, intermediate, and high risk). The risk of serious complications within 15 days increases according to the group: 1.6, 9.4, 30.6%; P<0.0001. Fifteen-day mortality rates also rise progressively in low-, intermediate-, and high-risk patients: 0.3, 6.1, and 17.1%; P<0.0001. The cross-validated risk estimate is 0.191 (s.e.=0.012). The optimism-corrected area under the receiver operating characteristic curve is 0.779 (95% CI, 0.717-0.840). CONCLUSIONS: We have developed and internally validated a prognostic index to predict serious complications with the potential to impact decision-making in patients with cancer and PE.

Nomogram-based prediction of survival in patients with advanced oesophagogastric adenocarcinoma receiving first-line chemotherapy: a multicenter prospective study in the era of trastuzumab.

BACKGROUND: To develop and validate a nomogram and web-based calculator to predict overall survival (OS) in Caucasian-advanced oesophagogastric adenocarcinoma (AOA) patients undergoing first-line combination chemotherapy. METHODS: Nine hundred twenty-four AOA patients treated at 28 Spanish teaching hospitals from January 2008 to September 2014 were used as derivation cohort. The result of an adjusted-Cox proportional hazards regression was represented as a nomogram and web-based calculator. The model was validated in 502 prospectively recruited patients treated between October 2014 and December 2016. Harrell's c-index was used to evaluate discrimination. RESULTS: The nomogram includes seven predictors associated with OS: HER2-positive tumours treated with trastuzumab, Eastern Cooperative Oncology Group performance status, number of metastatic sites, bone metastases, ascites, histological grade, and neutrophil-to-lymphocyte ratio. Median OS was 5.8 (95% confidence interval (CI), 4.5-6.6), 9.4 (95% CI, 8.5-10.6), and 14 months (95% CI, 11.8-16) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the derivation set and 4.6 (95% CI, 3.3-8.1), 12.7 (95% CI, 11.3-14.3), and 18.3 months (95% CI, 14.6-24.2) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the validation set. The nomogram is well-calibrated and reveals acceptable discriminatory capacity, with optimism-corrected c-indices of 0.618 (95% CI, 0.591-0.631) and 0.673 (95% CI, 0.636-0.709) in derivation and validation groups, respectively. The AGAMENON nomogram outperformed the Royal Marsden Hospital (c-index=0.583; P=0.00046) and Japan Clinical Oncology Group prognostic indices (c-index=0.611; P=0.03351). CONCLUSIONS: We developed and validated a straightforward model to predict survival in Caucasian AOA patients initiating first-line polychemotherapy. This model can contribute to inform clinical decision-making and optimise clinical trial design.

Epidermal growth factor receptor and epididymis invasion as prognostic biomarkers in clinical stage I testicular germ cell tumours.

BACKGROUND: Inguinal orchiectomy is curative in 70-80% of clinical stage I testicular germ cell tumours (CS I TGCT). The identification of patients who are at low risk of relapse is critical to avoid unnecessary treatment. The aim of this study is to explore EGFR, hMLH-1/hMSH-2 and microsatellite instability (MSI) as potential prognostic factors of recurrence in CS I TGCT. METHODS: Fifty-six CS I TGCT patients who underwent inguinal orchiectomy were included in this study. We analysed the relationship between clinicopathological and molecular factors with survival. Analysis of hMLH1, hMSH2 and EGFR expression was carried out by immunohistochemistry. Methylation status of the hMLH1 promoter was determined by pyrosequencing analysis in selected cases. EGFR exons 19, 20, 21 were analysed by PCR labeled-fragments and MSI status was determined using standard Multiplex MSI assays. RESULTS: Classical pathological factors such as lymphovascular invasion, high percentage of embryonal carcinoma, rete testis invasion or tumour size ≥4 cm showed a significant relationship with a higher risk of relapse. Additionally, it was found that an epididymis invasion proved to be a significant independent poor prognostic factor of recurrence (p = 0.001). hMLH1 or hMSH2 expression showed no significant association with risk of relapse and no MSI was found. EGFR expression was observed in 30.4% of samples and its expression was associated with higher risk of relapse (HR 3.5; 95% CI 1.3-9.8; p = 0.016). None of the cases presented EGFR kinase domain mutations. CONCLUSIONS: Epididymis invasion and EGFR expression, but not hMLH-1/hMSH-2 or MSI, could be potentially useful as new prognostic factors of recurrence for CS I TGCT.

Health-related quality of life in well-differentiated metastatic gastroenteropancreatic neuroendocrine tumors.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare neoplasms capable of producing hormones. The development of new treatments has improved progression-free survival, albeit with increased toxicity. Health-related quality of life (HRQoL) has become an important endpoint in clinical research to evaluate patients' well-being in such a contradictory scenario. In this review, we examine key reported outcomes across clinical studies exploring HRQoL in patients with GEP-NETs. We have conducted a review of the literature using PubMed, The Cochrane Library, EMBASE, and Google Scholar. Selection criteria for articles were (1) publication in English between 1995 and 2014, (2) patients with GEP-NET, and (3) analysis of HRQoL, including mental health and psychological symptoms. Forty-nine studies met the inclusion criteria (31 clinical trials, 14 observational studies, and 4 developments of NET-specific HRQoL instruments). The scope and nature of the literature was diverse with 27 instruments used to measure aspects of HRQoL. EORTC QLQ-C30 was the most frequently used, in 38 of the 49 studies. Standardized measures revealed that in spite of generally good HRQoL, GEP-NET patients have specific psychological and physical complaints. The clinical benefit of somatostatin analogs and sunitinib has been clearly supported by HRQoL assessment. Improvement in HRQoL scores or symptom relief over time was also reported in 14 trials of peptide receptor radionuclide therapy, however the absence of randomized studies obviate definitive conclusions. We have also identified several unanswered questions that should be addressed in further research concerning chemotherapy, everolimus, surgery, local ablative therapies, and chemoembolization. Future research should incorporate GEP-NET-specific HRQoL instruments into phase III trials. This review may help both clinicians and researchers to select the most appropriate tools to assess changes in HRQoL in this population.

Prognostic value of computed tomography in acute pulmonary thromboembolism. / Valor pronóstico de la tomografía computarizada en la tromboembolia pulmonar aguda.

In addition to being the standard reference for the diagnosis of acute pulmonary thromboembolism, CT angiography of the pulmonary arteries can also provide valuable information about the patient's prognosis. Although which imaging findings are useful for prognosis remains controversial, signs of right ventricular dysfunction on CT are now included in clinical algorithms for the management of pulmonary thromboembolism. However, the optimal method for obtaining these measurements while maintaining a balance between the ease of use necessary to include their evaluation in our daily activity and the loss of precision in its predictive capacity remains to be determined. Moreover, other variables associated with pulmonary thromboembolism that often go unobserved can complement the prognostic information we can offer to clinicians. This review aims to clarify some of the more controversial aspects related to the prognostic value of CT in patients with pulmonary embolisms according to the available evidence. Knowing which variables are becoming more important in the prognosis, how to detect them, and why it is important to include them in our reports will help improve the management of patients with pulmonary embolism.

Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin.

Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort 1), G1/2 gastrointestinal (Cohort 2), G1/2 pancreatic (Cohort 3) and G3 gastroenteropancreatic (GEP) (Cohort 4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month clinical benefit rate (CBR) for cohorts 1-3 and 9-month overall survival (OS) rate for Cohort 4. Secondary endpoints included objective response rate, duration of response, progression-free survival according to irRECIST, overall survival, and safety. Correlation of PD-L1 expression with efficacy was exploratory. The 9-month CBR was 25.9%/35.5%/25% for Cohorts 1, 2, and 3 respectively. The 9-month OS rate for Cohort 4 was 36.1%, surpassing the futility threshold. Benefit in Cohort 4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab is safe in NENs and shows modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS.

Association of Circulating Tumor Cells and Tumor Molecular Profile With Clinical Outcomes in Patients With Previously Untreated Metastatic Colorectal Cancer: A Pooled Analysis of the Phase III VISNÚ-1 and Phase II VISNÚ-2 Randomized Trials.

BACKGROUND: The bCTC count is a well-established prognostic biomarker in mCRC, as well as in other tumor types. The aim of this analysis was to evaluate the prognostic/predictive role of the bCTC count (≥3 vs. <3) in previously untreated mCRC. PATIENTS AND METHODS: The study involved 589 untreated mCRC patients included in the intention-to-treat population of 2 randomized clinical trials (phase III VISNU-1 [NCT01640405] and phase II VISNU-2 [NCT01640444] studies). RESULTS: Of the 589 patients, 349 (59.2%) had bCTC≥3 and 240 (40.7%) had bCTC<3. Multivariate analysis showed that the bCTC count is an independent prognostic factor for overall survival (OS) (HR 0.59, 95% CI 0.48-0.72; P = 0.000) and potential for progression-free survival (PFS) (P = 0.0549). Median OS was 32.9 and 19.5 months in patients with bCTC<3 and bCTC≥3 (P <0.001), respectively. This effect was also observed comparing OS in RASwt patients from both studies. Other prognostic factors were: ECOG-PS, primary tumor site, number of metastatic sites and surgery of the primary tumor. Median OS was lower for patients treated with anti-VEGF versus anti-EGFR (22.3 vs. 33.3 months, P <0.0001) while there were no significant differences in PFS according to the targeted treatment received. CONCLUSION: This post-hoc analysis of 2 randomized studies confirms the poor prognosis of patients with bCTC≥3 but this is not associated with other adverse independent prognostic factors such as RAS/BRAF mutations.

Sex and gender disparities in patients with advanced gastroesophageal adenocarcinoma: data from the AGAMENON-SEOM registry.

BACKGROUND: Recommendations for research articles include the use of the term sex when reporting biological factors and gender for identities or psychosocial or cultural factors. There is an increasing awareness of incorporating the effect of sex and gender on cancer outcomes. Thus, these types of analyses for advanced gastroesophageal adenocarcinoma are relevant. PATIENTS AND METHODS: Patients with advanced gastroesophageal adenocarcinoma from the Spanish AGAMENON-SEOM registry treated with first-line combination chemotherapy were selected. Epidemiology, characteristics of the disease, treatment selection, and results were examined according to sex. RESULTS: This analysis included 3274 advanced gastroesophageal adenocarcinoma patients treated with combination chemotherapy between 2008 and 2021: 2313 (70.7%) men and 961 (29.3%) women. Tumors in females were more frequently HER2-negative (67.8% versus 60.8%; P < 0.0001), grade 3 (45.4% versus 36.8%; P < 0.001), diffuse (43.3% versus 26.5%; P < 0.0001), and signet ring cell histology (40.5 versus 23.9%; P < 0.0001). Peritoneal spread was more common in women (58.6% versus 38.9%; P < 0.0001), while liver burden was lower (58.9% versus 71.1%; P < 0.0001). There were no significant differences in treatment recommendation. Treatment doses, density, and duration were comparable between sexes. Women experienced more diarrhea (46% versus 37%; P < 0.0001), neutropenia (51% versus 43%; P < 0.0001), and anemia (62% versus 57%; P < 0.0001). After a median 59.6-month follow-up [95% confidence interval (CI) 54.5-70.8], there were no statistically significant differences between the sexes in progression-free survival [6.21 months (95% CI 5.8-6.5 months) versus 6.08 months (95% CI 5.8-6.3 months); log-rank test, χ2 = 0.1, 1 df, P = 0.8] or in overall survival [10.6 months (95% CI 9.8-11.1 months) versus 10.9 months (95% CI 10.4-11.4 months); log-rank test: χ2 = 0.6, 1 df, P = 0.5]. CONCLUSION: This sex analysis of patients with advanced gastroesophageal adenocarcinoma from the AGAMENON-SEOM registry receiving first-line polychemotherapy found no differences in survival. Although women had worse prognostic histopathology, metastatic disease pattern, and greater toxicity, treatment allocation and compliance were equivalent.

Impact of adjuvant therapy toxicity on quality of life and emotional symptoms in patients with colon cancer: a latent class analysis.

OBJECTIVE: To identify distinct trajectories of toxicity in colorectal cancer (CRC) patients after adjuvant chemotherapy and its impact on quality of life (QoL) and psychological symptoms. METHODS: A prospective, multicenter study was conducted in 157 patients. A latent class analysis defined the unobserved latent constructs that can be predicted as symptom clusters, considering the intensity of four types of adverse events (AEs). Patients completed EORTC-QLQ-C30, BSI-18, PDRQ-9, and DRS scales. RESULTS: Ninety-six percent had some degree of toxicity, with grades 3-4 being the most common: neurotoxicity (7.2%), hematological (13.1%), digestive (5.2%), and skin toxicity (1.4%). Three distinct latent classes were identified (high [72.5%], mild [16.9%], and low [10.6%] toxicity). Patients with high toxicity had the worst QoL scores and moderately high somatization and psychological distress scores. CONCLUSIONS: Adjuvant chemotherapy for CRC was associated with frequent toxicity that negatively impacted QoL and psychological wellbeing.

Social support, coping strategies and sociodemographic factors in women with breast cancer.

INTRODUCTION: The aim of this study was to analyze the associations between perceived social support and sociodemographic variables on coping strategies. METHODS: A prospective, cross-sectional, multicenter study was conducted in 404 women with resected, non-metastatic breast cancer. Participants completed questionnaires: perceived social support (MSPSS), coping strategies (Mini-MAC), and psychological distress (BSI-18). RESULTS: Sociodemographic factors as age, education, and partnership status were associated with coping strategies. As for maladaptive strategies, hopelessness was more frequent in older people and lower educational level; fatalism in older and single people, and cognitive avoidance was associated with lower educational level. Suppor t from family, friends, and partners was associated with a greater fighting spirit. In contrast, high psychological distress (anxiety and depression) was associated with greater use of maladaptive strategies. CONCLUSION: Young people, a high level of education, having a partner, low psychological distress, and seeking social support were associated with the use of adaptive cancer coping strategies.

Use of healthcare REsources and associated COsts in controlled versus uncontrolled carcinoid SYndrome in patients with neuroendocrine tumours: the RECOSY study.

PURPOSE: To report healthcare resource use and associated costs in controlled versus uncontrolled carcinoid syndrome (CS) in patients with neuroendocrine tumours. METHODS: A cross-sectional, non-interventional multicentre study was conducted with retrospective data analysis. Resource use was compared between two patient groups: those with controlled CS (> 12 months with no uncontrolled CS episodes) and uncontrolled CS (< 12 months since last uncontrolled episode). Patients were matched for age, sex, and origin and grade of tumour. When no matching patients were available, data from deceased patients were used. Information on healthcare resource use came from review of medical records, patient history and physician reports. Working capacity was assessed using the Work Productivity and Activity Impairment General Health questionnaire. RESULTS: Twenty-six university hospitals in Spain participated, between July 2017 and April 2018. 137 patients were enrolled; 104 were analysed (2 groups of 52). Patients with uncontrolled CS had 10 times more emergency department (ED) visits (mean 1.0 vs 0.10 visits; P = 0.0167), were more likely to have a hospital admission (40.4% vs 19.2%; P = 0.0116) and had longer hospital stays (mean 7.87 vs 2.10 days; P = 0.0178) than those with controlled CS. This corresponded to higher annual hospitalisation costs (mean €5511.59 vs €1457.22; P = 0.028) and ED costs (€161.25 vs €14.85; P = 0.0236). The mean annual total healthcare costs were 60.0% higher in patients with uncontrolled than controlled CS (P = NS). CONCLUSION: This study quantifies higher health resource use, and higher hospitalisation and ED costs in patients with uncontrolled CS. Better control of CS may result 3in lower medical costs.

Rationale, design and methodology of TESEO study: a registry of thrombosis and neoplasia of SEOM (Spanish Society of Medical Oncology).

BACKGROUND AND RATIONALE: Thromboembolic complications are a serious, preventable and common event in cancer patients that contributes to increasing morbidity and mortality. Despite increasing knowledge on cancer-associated thrombosis (CAT), there are still several aspects of diagnosis, clinical management, treatment and prognosis with uncertainties that are under-represented in randomized clinical trials. For this reason, the Spanish Society of Medical Oncology (SEOM) launched in June 2018 a registry of CAT. METHODS/DESIGN: TESEO is an ongoing prospective, non-interventional, multicentric study in consecutive cancer patients with newly diagnosed of thromboembolic event (TEE). Eligibility criteria include being > 18 years with a histologically confirmed diagnosis of cancer and a symptomatic or incidental TEE confirmed with an imaging technique in the previous month or any time after the cancer diagnosis and signing of informed consent. The study consists of two types of integrated but independent prospective registries. Regular CAT sub-registry includes information on patient's cancer´s characteristics, anticoagulant treatment provided and outcome data. Special CAT sub-registry includes variables related to special situations of CAT that comprise patients with severe kidney failure, thrombocytopenia, high risk of bleeding related to the cancer or with coexistence of bleeding and patients who receive new treatments such a targeted therapy, antiangiogenics agents and immunotherapy. The registry considers the status of the cancer and the time to assess how the prognosis is changed based on when the thrombus occurs. Some outcomes such as rethrombosis, major bleeding, tumor progression and survival will be valued in various time intervals including 1, 3, 6 and 12 months after the even in the first year; and then every 6 months until the patient's death. RESULTS: After 18 months and with 35 centers and researchers, the registry has 1128 patients. CONCLUSION: TESEO registry will provide clinical real-world evidence for prevention, treatment and complications of CAT in different scenarios that are under-represented in randomized clinical trials.

Incidence, patterns of care and prognostic factors for outcome of gastroenteropancreatic neuroendocrine tumors (GEP-NETs): results from the National Cancer Registry of Spain (RGETNE).

BACKGROUND: Neuroendocrine tumors (NETs) are an unusual family of neoplasms with a wide and complex spectrum of clinical behavior. Here, we present the first report of a National Cancer Registry of gastroenteropancreatic neuroendocrine tumors from a Southern European country. PATIENTS AND METHODS: Data was provided online at www.retegep.net by participating centers and assessed for internal consistency by external independent reviewers. RESULTS: The study cohort comprised 907 tumors. The most common tumor types were carcinoids (55%), pancreatic nonfunctional tumors (20%), metastatic NETs of unknown primary (9%), insulinomas (8%) and gastrinomas (4%). Forty-four percent presented with distant disease at diagnosis, most often those from small intestine (65%), colon (48%), rectum (40%) and pancreas (38%), being most unusual in appendix primaries (1.3%). Stage at diagnosis varied significantly according to sex, localization of primary tumor, tumor type and grade. Overall 5-year survival was 75.4% (95% confidence interval 71.3% to 79.5%) and was significantly greater in women, younger patients and patients with hormonal syndrome and early stage or lower grade tumors. Prognosis also differed according to tumor type and primary tumor site. However, stage and Ki-67 index were the only independent predictors for survival. CONCLUSION: This national database reveals relevant information regarding epidemiology, current clinical practices and prognosis of NETs in Spain, providing valuable insights that may contribute to understand regional disparities in the incidence, patterns of care and survival of this heterogeneous disease across different continents and countries.

Coping strategies and depressive symptoms in cancer patients.

INTRODUCTION: Depression in cancer patients is prevalent and negatively impacts their quality of life. Likewise, it correlates with lower overall survival. The aim of this work is to analyze whether different coping strategies, as well as sociodemographic and clinical factors are associated with the presence of depressive symptoms in individuals with a resected, non-metastatic neoplasm about to initiate adjuvant chemotherapy. METHODS: NEOcoping is a cross-sectional, prospective, observational, multicenter study. Clinical (tumor site and stage, time to diagnosis, risk of recurrence, and type of adjuvant treatment) and sociodemographic characteristics (age, gender, marital status, educational level, occupational sector, and employment status), coping strategies (Mini-MAC scale), and depressive symptoms (BSI scale) were collected. A two-block linear regression model was performed to determine the predictive variables of depressive symptoms. RESULTS: 524 adults with resected, non-metastatic cancer were recruited. Twenty-six percent of patients have clinically significant depressive symptoms. Being female, < 40 years of age, having breast and stomach cancer, and > 50% chance of recurrence were associated with increased risk of depression. Likewise, depression was associated with greater helplessness and anxious preoccupation, and less fighting spirit. Age, gender, and risk of recurrence accounted for only 7% of the variance in depressive symptoms. Including coping strategies in the regression analysis significantly increased the variance explained (48.5%). CONCLUSION: Early psychological intervention in patients with maladaptive coping strategies may modulate the onset of depressive symptoms, especially in those at higher risk for depression.

SEOM clinical guideline for the diagnosis and treatment of gastric cancer (GC) and gastroesophageal junction adenocarcinoma (GEJA) (2019).

Gastric cancer (GC) is the fifth most common cancer worldwide with a varied geographic distribution and an aggressive behavior. In Spain, it represents the sixth cause of cancer death. In Western countries, the incidence is decreasing slightly, with an increase in gastroesophageal junction adenocarcinoma (GEJA), a different entity that we separate specifically in the guideline. Molecular biology advances have been done recently, but do not yet lead to the choice in treatment approach except in advanced disease with overexpression of HER2. Endoscopic resection in very early stage, perioperative chemotherapy in locally advanced tumors and preliminary immune therapy resulting in advanced disease are the main treatment innovations in the GC/GEJA treatment. We describe the different evidences and recommendations following the statements of the American College of Physicians.

The popularity of neurology in Spain: An analysis of specialty selection. / Popularidad de Neurología en España: análisis de la elección de la especialidad.

INTRODUCTION: Neurology is one of the medical specialties offered each year to residency training candidates. This project analyses the data associated with candidates choosing neurology residency programmes in recent years. METHODS: Data related to specialty selection were obtained from official reports by the Spanish Ministry of Health, Social Services, and Equality. Information was collected on several characteristics of teaching centres: availability of stroke units, endovascular intervention, national reference clinics for neurology, specific on-call shifts for neurology residents, and links with medical schools or national research networks. RESULTS: The median selection list position of candidates selecting neurology training has been higher year on year; neurology was among the 4 most popular residency programmes in 2016. Potential residents were mainly female, Spanish, and had good academic results. The median number of hospitals with higher numbers of beds, endovascular intervention, stroke units, and national reference clinics for neurology is significantly lower. This is also true when centers are analysed by presence of specific on-call shifts for neurology residents and association with medical schools or national research networks. The centres selected by candidates with the highest median selection list position in 2012-2016 were the Clínico San Carlos, 12 de Octubre, and Vall d'Hebron university hospitals. CONCLUSIONS: Neurology has gradually improved in residency selection choices and is now one of the 4 most popular options. Potential residents prefer larger centres which are more demanding in terms of patient care and which perform more research activity.

Optimal duration of first-line chemotherapy for advanced gastric cancer: data from the AGAMENON registry.

BACKGROUND: The optimal duration of first-line chemotherapy for patients with advanced gastric cancer is unknown. Diverse clinical trials have proposed different strategies including limited treatment, maintenance of some drugs, or treatment until progression. METHOD: The sample comprises patients from the AGAMENON multicenter registry without progression after second evaluation of response. The objective was to explore the optimal duration of first-line chemotherapy. A frailty multi-state model was conducted. RESULTS: 415 patients were divided into three strata: discontinuation of platinum and maintenance with fluoropyrimidine until progression (30%, n = 123), complete treatment withdrawal prior to progression (52%, n = 216), and full treatment until progression (18%, n = 76). The hazard of tumor progression decreased by 19% per month with the full treatment regimen. However, we found no evidence that fluoropyrimidine maintenance (hazard ratio [HR] 1.07, confidence interval [CI] 95%, 0.69-1.65) worsened progression-free survival (PFS) with respect to treatment until progression. Predictive factors for PFS were ECOG performance status, ≥ 3 metastatic sites, prior tumor response, and bone metastases. Toxicity grade 3/4 was more common in those who continued the full treatment until progression vs fluoropyrimidine maintenance (16% vs 6%). CONCLUSION: The longer duration of the full initial regimen exerted a protective effect on the patients of this registry. Platinum discontinuation followed by fluoropyrimidine maintenance yields comparable efficacy to treatment up to PD, with a lower rate of serious adverse events.