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.

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.

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.

A prognostic model to identify short survival expectancy of medical oncology patients at the time of hospital discharge.

BACKGROUND: Hospitalization of cancer patients is associated with poor overall survival, but prognostic misclassification may lead to suboptimal therapeutic decisions and transitions of care. No model is currently available for stratifying the heterogeneous population of oncological patients after a hospital admission to a general Medical Oncology ward. We developed a multivariable prognostic model based on readily available and objective clinical data to estimate survival in oncological patients after hospital discharge. METHODS: A multivariable model and nomogram for overall survival after hospital discharge was developed in a retrospective training cohort and prospectively validated in an independent set of adult patients with solid tumors and a first admission to a unit of medical oncology. Performance of the model was assessed by C-index and Kaplan-Meier survival curves stratified by risk categories. RESULTS: From a population of 1089 patients with a first hospitalization, 757 patients were included in the training group [median survival, 43 weeks; 95% confidence interval (CI), 37-51 weeks] and 200 patients in the validation cohort (median survival, 44 weeks; 95% CI, 34 weeks-not reached). An accelerated failure time log-normal model was built, including five variables (primary tumor, stage, cause of admission, active treatment, and age). The C-index was 0.71 (95% CI, 0.69-0.73), with a good calibration, and adequate validation in the prospective cohort (C-index: 0.69; 95% CI, 0.65-0.74). Median survival in three predefined model-based risk groups was 10.7 weeks (high), 27.0 weeks (intermediate), and 3 years (low) in the training cohort, with comparable values in the validation cohort. CONCLUSIONS: In oncological patients, individualized predictions of survival after hospitalization were provided by a simple and validated model. Further evaluation of the model might determine whether its use improves shared decision making at discharge.

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 (AU)

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.

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.

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 (AU)

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 (AU)

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.

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.

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.

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.

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.

Trifluridine/Tipiracil (TAS-102) for refractory metastatic colorectal cancer in clinical practice: a feasible alternative for patients with good performance status.

INTRODUCTION: Our aim was to assess efficacy and safety and prognostic factors associated with TAS-102 in clinical practice. METHOD: Retrospective, multicenter, and observational study including patients with advanced refractory colorectal cancer who started TAS-102 between March 2016 and August 2018. The primary end point was overall survival (OS). Secondary end points included progression-free survival, toxicity and analyze prognostic factors present at the beginning of TAS-102. RESULT: 84 patients were evaluable. The median OS was 8.30 (95% CI 6.23-9.87) months and PFS was 2.62 (95% CI 2.36-3.05) months. In multivariate analysis, ECOG 0 and reduced dose combined with more cycles were associated with better prognosis. Patients with an ECOG > 0 had worse prognosis (HR 3.34, 95% CI 1.09-10.27, p = 0.035). 95.2% experienced some type of adverse effect and 45.2% had grade ≥ 3 toxicities. CONCLUSION: Results suggest reconsidering TAS-102 in patients with ECOG > 0, something that should be investigated in prospective randomized clinical trials.

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. CONCLUSION: Our findings point toward the importance of developing interventions that decrease depression and sleep problems in cancer.