Response of cows with osteomalacia grazing sub-tropical native pastures to phosphorus supplementation with loose mineral mix or feed blocks.

Osteomalacia outbreaks often occur in cattle grazing native pastures in regions with endemic phosphorous (P) deficiency. This study evaluated the responses of two groups of cows, initially with clinical signs of chronic P deficiency, to P supplements (100 g P/kg) offered ad libitum for 13 weeks as a loose mineral mix (LMM group) or the same mineral mix offered as blocks (BMM group). Half of the cows in each group were categorized as 'with' or 'without' severe osteopenia according to a test that depended on the resistance to penetration of a needle through the left lateral process of the L4-L5 lumbar vertebra. The groups grazed two paddocks that were switched each 3 weeks. The liveweight, supplement intakes, and the P-concentrations in soil, forage, blood, and external cortical bone (ECB) of the ribs were measured. The bicarbonate-extractable P in soil was 3.5 mg/kg. The mean of total P in forage (0.95 g/kg/DM), inorganic P in serum (iP, 0.96 mmol/L), and total P in the ECB of the ribs (85 mg/mL) at the beginning of the experiment were all low and consistent with severe chronic P deficiency. The P supplementation allowed clinical recovery in 18/20 cows with their serum and ECB P and calcium approaching normal values and in the two remaining cows the only sign was abnormal gait. Cows consumed more of the LMM than BMM supplement (means 8.3 and 6.6 g P/day, respectively). After 13 weeks cows initially classified as 'with severe osteopenia' and supplemented with LMM had higher (P < 0.05) final liveweight (difference = 21.6 kg), iP (difference = 0.74 mmol/L), bone Ca (difference = 65.7 mg/mL) and bone P (difference = 26.5 mg/mL) concentrations and lower (P < 0.01) final serum Ca/iP ratio (difference = -0.65) than cows with severe osteopenia but supplemented with BMM. The treatment of severe P deficiency cows grazing P deficient sub-tropical grasslands by P supplementation for 13 weeks was more effective with LMM than BMM.

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.

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 (AU)

Normobaric Hypoxia Exposure on Substrate Oxidation Pattern: Sex Differences.

CONTEXT: Hypoxic exposure has been associated with a metabolic perturbation that might affect basal energy expenditure (BEE). OBJECTIVE: The aim was to examine the metabolic response during hypoxic exposure of men and women adults. DESIGN: Crossover design with two experimental trials: normoxic and hypoxic exposure. SUBJECTS AND METHODS: Twenty-nine healthy subjects (14 women) participated in (1) control study (NOR), subjected first to normoxic exposure (FiO2 = 20.9%) and (2) after that, to passive normobaric hypoxic exposure study (HYP) (FiO2 = 15%). Respiratory gases and blood glucose samples were recorded every hour in hypoxia chamber (8 points in total), and blood lactate samples were collected at baseline, at 4 and 7 h to exposure. RESULTS: In females, basal energy expenditure was significantly higher at 2h, 4h, 6h and 7h compared with NOR group. Also, BEE was lower in females compared with men from 2h of hypoxia exposure. In the HYP group the blood lactate concentration increased significantly at 4h and 7 h relative to NOR group (P < 0.05) in males. CONCLUSION: An exposure to moderate normobaric hypoxia did not alter metabolic response, but induced a different response on substrate oxidation in adults men and women.

Prognostic factors in advanced pancreatic ductal adenocarcinoma patients-receiving second-line treatment: a single institution experience

Background Second-line (2L) treatments for advanced pancreatic ductal adenocarcinoma (PDAC) achieve a modest benefit at the expense of potential toxicity. In the absence of predictive factors of response, the identification of prognostic factors could help in the therapeutic decisions-making. The purpose of this study was to assess the prognostic factors associated with shorter survival in patients with advanced PDAC who received 2L treatment. Methods We conducted a single institution retrospective study, which included all patients with advanced PDAC who received 2L treatment between September 2006 and February 2020 at La Paz University Hospital, Madrid (Spain). Significant variables in the logistic regression model were used to create a prognostic score. Results We included 108 patients. The median overall survival (OS) was 5.10 months (95%CI 4.02–6.17). In the multivariate analysis, time to progression (TTP) shorter than 4 months after first-line treatment (OR 4.53 [95%CI 1.28–16.00] p = 0.01), neutrophil-to-lymphocyte ratio (NLR) greater than 3 at the beginning of 2L (OR 9.07 [95%CI 1.82–45.16] p = 0.01) and CA-19.9 level higher than the upper limit of normal at the beginning of 2L (OR 7.83 [95%CI 1.30–49.97] p = 0.02) were independently associated with OS shorter than 3 months. The prognostic score classified patients into three prognostic groups (good, intermediate and poor) with significant differences in OS (p < 0.001). Conclusions TTP shorter than 4 months after first-line treatment, NLR greater than 3 and CA-19.9 level higher than the upper limit of normal at the beginning of 2L were associated with shorter overall survival. We developed a prognostic score that classifies patients with advanced PDAC into three prognostic groups after progression to the first-line. This score could help in the decision-making for 2L treatment (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.

Prognostic factors in advanced pancreatic ductal adenocarcinoma patients-receiving second-line treatment: a single institution experience.

BACKGROUND: Second-line (2L) treatments for advanced pancreatic ductal adenocarcinoma (PDAC) achieve a modest benefit at the expense of potential toxicity. In the absence of predictive factors of response, the identification of prognostic factors could help in the therapeutic decisions-making. The purpose of this study was to assess the prognostic factors associated with shorter survival in patients with advanced PDAC who received 2L treatment. METHODS: We conducted a single institution retrospective study, which included all patients with advanced PDAC who received 2L treatment between September 2006 and February 2020 at La Paz University Hospital, Madrid (Spain). Significant variables in the logistic regression model were used to create a prognostic score. RESULTS: We included 108 patients. The median overall survival (OS) was 5.10 months (95%CI 4.02-6.17). In the multivariate analysis, time to progression (TTP) shorter than 4 months after first-line treatment (OR 4.53 [95%CI 1.28-16.00] p = 0.01), neutrophil-to-lymphocyte ratio (NLR) greater than 3 at the beginning of 2L (OR 9.07 [95%CI 1.82-45.16] p = 0.01) and CA-19.9 level higher than the upper limit of normal at the beginning of 2L (OR 7.83 [95%CI 1.30-49.97] p = 0.02) were independently associated with OS shorter than 3 months. The prognostic score classified patients into three prognostic groups (good, intermediate and poor) with significant differences in OS (p < 0.001). CONCLUSIONS: TTP shorter than 4 months after first-line treatment, NLR greater than 3 and CA-19.9 level higher than the upper limit of normal at the beginning of 2L were associated with shorter overall survival. We developed a prognostic score that classifies patients with advanced PDAC into three prognostic groups after progression to the first-line. This score could help in the decision-making for 2L treatment.

Incidence of venous thromboembolic events in cancer patients receiving immunotherapy: a single-institution experience.

BACKGROUND: Cancer and cancer therapies have been associated with an increased incidence of venous thromboembolic events (VTE). However, the incidence of VTE in patients on immunotherapy has not been well characterized. The aim of this study was to assess the incidence of VTE in cancer patients receiving immunotherapy and ascertain its prognostic utility. MATERIALS AND METHODS: We conducted a single-institution retrospective study, including all cancer patients treated with anti-Programmed cell Death 1 (PD-1), anti-Programmed cell Death Ligand-1 (PD-L1), anti-Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4), a combination of anti-PD-1/anti-PD-L1 and anti-CTLA4 or a combination including any of these drugs with chemotherapy, antiangiogenic agents or both between June 2013 and April 2019 at La Paz University Hospital, Madrid (Spain). RESULTS: We selected 229 patients. VTE occurred in 16 of 229 patients (7%). VTE occurred more frequently in patients with lung cancer followed by melanoma. Female sex and melanoma were independently associated with an increased risk of VTE. 12 of 16 VTE (75%) were symptomatic. Progressive disease to immunotherapy [HR 31.60 (95% CI 11.44-87.22), p = 0.00], lung cancer [HR 2.55 (95% CI 1.34-4.86), p = 0.00] and melanoma [HR 2.42 (1.20-4.86), p = 0.01] were independently associated with shorter OS. VTE occurrence was not independently associated with shorter OS [HR 1.33 (95% CI 0.63-2.80), p = 0.44]. CONCLUSIONS: The incidence of VTE in cancer patients receiving immunotherapy in our study appeared to be similar to the incidence previously reported in other series of cancer patients treated with systemic therapies. VTE occurrence did not correlate with the prognosis. Further and prospective studies are needed to derive definitive conclusions.

Caracterização da fauna helmintológica de tamanduá-bandeira (Myrmecophaga tridactyla) e tamanduá-mirim (Tamandua tetradactyla) atropelados nas rodovias BR-050 e BR-455 (Minas Gerais, Brasil) / [Helmintological characterization of giant anteater (Myrmecophaga tridactyla) and lesser anteater (Tamandua tetradactyla) roadkilled on BR-050 and BR-455 highways (Minas Gerais, Brazil)]

O tamanduá-bandeira (Myrmecophaga tridactyla) e o tamanduá-mirim (Tamandua tetradactyla) são mamíferos xenartros amplamente distribuídos no território nacional. Apesar disso, suas populações estão em constante ameaça, principalmente o primeiro, categorizado como vulnerável de acordo com classificação da União Internacional para Conservação da Natureza. Diante disso e da escassez de estudos com endoparasitas nesses animais, objetivou-se descrever a helmintofauna dessas duas espécies de tamanduá, utilizando espécimes atropelados nas rodovias BR-050 e BR-455, região do Triângulo Mineiro, Minas Gerais, Brasil. Os animais foram submetidos à necropsia, tendo seus órgãos e conteúdo intestinal e estomacal examinados para recuperação de helmintos. Os parasitos coletados foram identificados com base em suas características morfológicas e morfométricas. As espécies/os gêneros caracterizados para M. tridactyla e T. tetradactyla, suas respectivas prevalências, bem como órgãos de origem, foram: Gaphidiops dissimilis (33,33% e 0%) no estômago; Gigantorhynchus echinodiscus (25% e 66,66%) no intestino delgado; Physaloptera magnipapilla (50% e 66,6%) no estômago; e Mathevotaenia spp. (25% e 66,66%) no intestino delgado. Physaloptera magnipapilla foi a espécie com os maiores índices de infecção, e novo registro de localização foi registrado para o nematódeo Graphidiops dissimilis. Detectou-se uma provável sobreposição da área de vida dos tamanduás estudados, bem como uma helmintofauna característica da região.(AU)

Myrmecophaga tridactyla, giant anteater and Tamandua tetradactyla, collared anteater are nationally widespread mammals. Despite that, their populations are in danger, especially the first one, categorized as vulnerable according to the International Union for Conservation of Nature. This study reports the occurrence of helminths in these two anteater species using road killed specimens from BR-050 and BR-455 highways, Triângulo Mineiro region, Minas Gerais state, Brazil. The species were necropsied, and their gastrointestinal organs and contents were opened and examined for parasite recovery. The identification was based on morphological and morphometric features. The species/ genera found for M. tridactyla and T. tetradactyla, their prevalence, as well the organs, were: Gaphidiops dissimilis (33.33% and 0%) in stomach; Gigantorhynchus echinodiscus (25% and 66.66%) in small intestine; Physaloptera magnipapilla (50% and 66.6%) in stomach and Mathevotaenia spp. (25% and 66.66%) in small intestine. Physaloptera magnipapilla was the most common species and a new location was reported for Graphidiops dissimilis. There is a probable overlap in the home range of these animals and a local helminth diversity was described on the study site.(AU)

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.

SEOM clinical practice guideline: management and prevention of febrile neutropenia in adults with solid tumors (2018)

Febrile neutropenia (FN) is a common dose-limiting toxicity of chemotherapy, with a profound impact on the evolution of patients with cancer, due to the potential development of serious complications, mortality, delays, and decrease in treatment intensity. This article seeks to present an updated clinical guideline, with recommendations regarding the diagnosis, prevention, and treatment of febrile neutropenia in adults with solid tumors. The aspects covered include how to properly approach the risk of microbial resistances, epidemiological aspects, considerations about the initial empirical approach adapted to the risk, special situations, and prevention of complications. A decision-making algorithm is included for use in the emergency department based on a new, validated tool, the Clinical Index of Stable Febrile Neutropenia, which can be used in patients with solid tumors who appear stable in the initial phase of neutropenic infections, and can help detect those at high risk for complications in whom early discharge must be avoided

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Calibration of parameters in Dynamic Energy Budget models using Direct-Search methods.

Dynamic Energy Budget (DEB) theory aims to capture the quantitative aspects of metabolism at the individual level, for all species. The parametrization of a DEB model is based on information obtained through the observation of natural populations and experimental research. Currently the DEB toolbox estimates these parameters using the Nelder-Mead Simplex method, a derivative-free direct-search method. However, this procedure presents some limitations regarding convergence and how to address constraints. Framed in the calibration of parameters in DEB theory, this work presents a numerical comparison between the Nelder-Mead Simplex method and the SID-PSM algorithm, a Directional Direct-Search method for which convergence can be established both for unconstrained and constrained problems. A hybrid version of the two methods, named as Simplex Directional Direct-Search, provides a robust and efficient algorithm, able to solve the constrained optimization problems resulting from the parametrization of the biological models.

SEOM clinical practice guideline: management and prevention of febrile neutropenia in adults with solid tumors (2018).

Febrile neutropenia (FN) is a common dose-limiting toxicity of chemotherapy, with a profound impact on the evolution of patients with cancer, due to the potential development of serious complications, mortality, delays, and decrease in treatment intensity. This article seeks to present an updated clinical guideline, with recommendations regarding the diagnosis, prevention, and treatment of febrile neutropenia in adults with solid tumors. The aspects covered include how to properly approach the risk of microbial resistances, epidemiological aspects, considerations about the initial empirical approach adapted to the risk, special situations, and prevention of complications. A decision-making algorithm is included for use in the emergency department based on a new, validated tool, the Clinical Index of Stable Febrile Neutropenia, which can be used in patients with solid tumors who appear stable in the initial phase of neutropenic infections, and can help detect those at high risk for complications in whom early discharge must be avoided.

Top ten errors of statistical analysis in observational studies for cancer research

Observational studies using registry data make it possible to compile quality information and can surpass clinical trials in some contexts. However, data heterogeneity, analytical complexity, and the diversity of aspects to be taken into account when interpreting results makes it easy for mistakes to be made and calls for mastery of statistical methodology. Some questionable research practices that include poor analytical data management are responsible for the low reproducibility of some results; yet, there is a paucity of information in the literature regarding specific statistical pitfalls of cancer studies. In addition to proposing how to avoid or solve them, this article seeks to expose ten common problematic situations in the analysis of cancer registries: convenience, dichotomization, stratification, regression to the mean, impact of sample size, competing risks, immortal time and survivor bias, management of missing values, and data dredging

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Key points to optimizing management and research on cancer-associated thrombosis

Despite the fact that thromboembolism is relatively common in oncology patients and that the interrelationship between thrombotic risk and specific mechanisms of tumorigenesis has long been known, many cardinal elements of prevention and treatment remain unresolved. Among the existing knowledge gaps, the need to validate the Ay scale and compare it to the Khorana index, develop, and standardize the use of predictive biomarkers for thrombotic risk, conduct clinical trials in thromboprophylaxis adapted to thrombotic risk, evaluate the efficacy and safety of direct anticoagulants, select patients who can benefit from anticoagulants for antitumor treatment, validate the EPIPHANY study decision tree to choose patients with low-risk pulmonary embolism, and accumulate more practical experience in special situations (rethrombosis, prolonged therapy beyond 6 months, etc.) are especially remarkable. These gray areas surrounding cancer-related thromboembolism explain why it continues to be a relatively common cause of serious events, at times interfering significantly with the development of new tumor-fighting strategies (AU)

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Key points to optimizing management and research on cancer-associated thrombosis.

Despite the fact that thromboembolism is relatively common in oncology patients and that the interrelationship between thrombotic risk and specific mechanisms of tumorigenesis has long been known, many cardinal elements of prevention and treatment remain unresolved. Among the existing knowledge gaps, the need to validate the Ay scale and compare it to the Khorana index, develop, and standardize the use of predictive biomarkers for thrombotic risk, conduct clinical trials in thromboprophylaxis adapted to thrombotic risk, evaluate the efficacy and safety of direct anticoagulants, select patients who can benefit from anticoagulants for antitumor treatment, validate the EPIPHANY study decision tree to choose patients with low-risk pulmonary embolism, and accumulate more practical experience in special situations (rethrombosis, prolonged therapy beyond 6 months, etc.) are especially remarkable. These gray areas surrounding cancer-related thromboembolism explain why it continues to be a relatively common cause of serious events, at times interfering significantly with the development of new tumor-fighting strategies.

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.

Top ten errors of statistical analysis in observational studies for cancer research.

Observational studies using registry data make it possible to compile quality information and can surpass clinical trials in some contexts. However, data heterogeneity, analytical complexity, and the diversity of aspects to be taken into account when interpreting results makes it easy for mistakes to be made and calls for mastery of statistical methodology. Some questionable research practices that include poor analytical data management are responsible for the low reproducibility of some results; yet, there is a paucity of information in the literature regarding specific statistical pitfalls of cancer studies. In addition to proposing how to avoid or solve them, this article seeks to expose ten common problematic situations in the analysis of cancer registries: convenience, dichotomization, stratification, regression to the mean, impact of sample size, competing risks, immortal time and survivor bias, management of missing values, and data dredging.

Clinical Outcome of Patients with Advanced Biliary Tract Cancer in a Dedicated Phase I Unit.

AIMS: Advanced biliary tract carcinomas (ABC) are malignancies with limited effective therapies for advanced disease. There is little published evidence of outcomes of ABC patients participating in phase I clinical trials. MATERIALS AND METHODS: Patient characteristics, treatment details and outcomes of ABC patients treated at a dedicated phase I unit were captured and analysed from case and trial records. RESULTS: In total, 123 ABC patients were included in the study, of which 48 patients participated in 41 different phase I trials; 75 (61%) did not participate due to rapid disease progression or patient choice. Molecular characterisation of tumours using a targeted panel was conducted in 15 (31%), yielding several potentially actionable mutations, including BRCA, PIK3CA, FGFR, AKT and PTEN loss. Of the 39 evaluable patients there was one exceptional responder. Eighteen (46%) other patients achieved stable disease as their best response, with a clinical benefit rate at 4 months of 10%. Treatment was generally well tolerated with grade 3 or 4 adverse events only observed in eight patients (17 %), of which six were drug related and led to trial discontinuation in one (3%), with no toxicity-related deaths. CONCLUSION: Carefully selected ABC patients have been found to tolerate experimental phase I clinical trials without excess toxicity. The aggressive nature of this disease warrants consideration of early referral to a phase I unit. Future work will require comprehensive molecular profiling in an attempt to understand the biology underlying the exceptional responders and to match patients in real-time to targeted therapies.