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.

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.

Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patients.

BACKGROUND: RAS assessment is mandatory for therapy decision in metastatic colorectal cancer (mCRC) patients. This determination is based on tumor tissue, however, genotyping of circulating tumor (ct)DNA offers clear advantages as a minimally invasive method that represents tumor heterogeneity. Our study aims to evaluate the use of ctDNA as an alternative for determining baseline RAS status and subsequent monitoring of RAS mutations during therapy as a component of routine clinical practice. PATIENTS AND METHODS: RAS mutational status in plasma was evaluated in mCRC patients by OncoBEAM™ RAS CRC assay. Concordance of results in plasma and tissue was retrospectively evaluated. RAS mutations were also prospectively monitored in longitudinal plasma samples from selected patients. RESULTS: Analysis of RAS in tissue and plasma samples from 115 mCRC patients showed a 93% overall agreement. Plasma/tissue RAS discrepancies were mainly explained by spatial and temporal tumor heterogeneity. Analysis of clinico-pathological features showed that the site of metastasis (i.e. peritoneal, lung), the histology of the tumor (i.e. mucinous) and administration of treatment previous to blood collection negatively impacted the detection of RAS in ctDNA. In patients with baseline mutant RAS tumors treated with chemotherapy/antiangiogenic, longitudinal analysis of RAS ctDNA mirrored response to treatment, being an early predictor of response. In patients RAS wt, longitudinal monitoring of RAS ctDNA revealed that OncoBEAM was useful to detect emergence of RAS mutations during anti-EGFR treatment. CONCLUSION: The high overall agreement in RAS mutational assessment between plasma and tissue supports blood-based testing with OncoBEAM™ as a viable alternative for genotyping RAS of mCRC patients in routine clinical practice. Our study describes practical clinico-pathological specifications to optimize RAS ctDNA determination. Moreover, OncoBEAM™ is useful to monitor RAS in patients undergoing systemic therapy to detect resistance and evaluate the efficacy of particular treatments.

Multicenter phase II study of oxaliplatin and sorafenib in advanced gastric adenocarcinoma after failure of cisplatin and fluoropyrimidine treatment. A GEMCAD study.

BACKGROUND: Cisplatin and fluoropyrimidine (CF) are standard first- line treatment in advanced gastric cancer, but no second-line treatment has yet been established. We present a phase II study in which we evaluated the efficacy and toxicity of the combination of Sorafenib (S), and Oxaliplatin as second-line therapy. METHODS: Patients with progressive gastric adenocarcinoma after CF- first-line, ECOG 0-2, and measurable disease were included. The primary objective was PFS. Treatment doses were Oxaliplatin 130 mg/m²/3 weeks and Sorafenib 800 mg/bid/d. RESULTS: We included 40 patients. CR was 2.5% and SD was 47.2%. Grade 3-4 toxic effects were neutropenia (9.8%), thrombocytopenia (7.3%), neurotoxicity (4.9%) and diarrhea (4.9%). Median PFS was 3 months (95%CI: 2.3-4.1) and median OS was 6.5 months (95% CI: 5.2-9.6). Time to progression (TTP) to first line therapy was a prognosis factor. Median OS was 9.7 months when time-to-progression during first-line chemotherapy was >6 months and 5.6 m when it was <6 months (p = 0.04). CONCLUSIONS: Time-to-progression under a CF-based first-line therapy determines subgroups of GC patients with different prognosis. The combination of Oxaliplatin-Sorafenib in advanced GC patients previously treated with CF appears safe, but our results do not support the implementation of a phase III trial.

Radiofrequency-assisted transection of the pancreas vs stapler in distal pancreatectomy: a propensity score matched cohort analysis.

To demonstrate the efficacy of radiofrequency for pancreatic stump closure in reducing the incidence of postoperative pancreatic fistula (POPF) in distal pancreatectomy (DP) compared with mechanical transection methods. Despite all the different techniques of pancreatic stump closure proposed for DP, best practice for avoiding POPF remains an unresolved issue, with an incidence of up to 30% regardless of center volume or surgical expertise. DP was performed in a cohort of patients by applying radiofrequency to stump closure (RF Group) and compared with mechanical closure (Control Group). A propensity score (PS) matched cohort study was carried out to minimize bias from nonrandomized treatment assignment. Cohorts were matched by PS accounting for factors significantly associated with either undergoing RF transection or mechanical closure through logistic regression analysis. The primary end-point was the incidence of clinically relevant POPF (CR-POPF). Of 89 patients included in the whole cohort, 13 case patients from the RF-Group were 1:1 matched to 13 control patients. In both the first independent analysis of unmatched data and subsequent adjustment to the overall propensity score-matched cohort, a higher rate of CR-POPF in the Control Group compared with the RF-Group was detected (25.4% vs 5.3%, p = 0.049 and 53.8% vs 0%; p = 0.016 respectively). The RF Group showed better outcomes in terms of readmission rate (46.2% vs 0%, p = 0.031). No significant differences were observed in terms of mortality, major complications (30.8% vs 0%, p = 0.063) or length of hospital stay (5.7 vs 5.2 days, p = 0.89). Findings suggest that the RF-assisted technique is more efficacious in reducing CR-POPF than mechanical pancreatic stump closure.

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.

Incidental versus symptomatic venous thrombosis in cancer: a prospective observational study of 340 consecutive patients.

BACKGROUND: The clinical significance of incidental venous thrombosis (IVT) is uncertain. The objective of this study was to compare the clinical characteristics and the outcome of cancer patients with IVT with those of patients with symptomatic venous thrombosis (SVT). PATIENTS AND METHODS: Prospective observational study enrolling consecutive cancer patients newly diagnosed with venous thromboembolism (May 2006-April 2009). Diagnosis of IVT was based on vascular filling defects in scheduled computed tomography scans in the absence of clinical symptoms. Anticoagulant therapy was routinely prescribed regardless of SVT or IVT. RESULTS: IVT was diagnosed in 94 out of 340 (28%) patients. Patients with IVT were older (63.7 ± 10.5 versus 60.8 ± 10.5 years, P = 0.035), more frequently had metastatic cancer (82% versus 65%, P = 0.01) and were less likely to be receiving chemotherapy at the time of the thrombotic event (53% versus 67%, P = 0.018). Mean follow-up was 477 days. A lower risk of venous rethromboses was observed in patients with IVT (log-rank P = 0.043), with no differences in major bleeding and overall survival compared with SVT patients. CONCLUSIONS: A high proportion of venous thrombotic events in cancer patients are diagnosed incidentally during scheduled imaging. Prospective controlled trials evaluating the optimal therapy in this setting are required.

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.

Molecular biology of androgen-independent prostate cancer: the role of the androgen receptor pathway.

Prostate cancer (PC) cells express the androgen receptor (AR) and need the presence of androgens to survive. Androgen suppression is the gold standard first-line therapy for metastatic disease. Almost all PC patients initially respond to hormonal therapy, but most of them gradually develop resistance to castration. There is evidence that these tumours that are considered castration-resistant continue to depend on AR signalling. Several mechanisms that enhance AR signalling in an androgen-depleted environment have been elucidated: (1) AR mutations that allow activation by low androgen levels or by other endogenous steroids, (2) AR amplification and/or overexpression, (3) increased local intracrine synthesis of androgens, (4) changes in AR cofactors and (5) cross-talk with cytokines and growth factors. Today, there are a number of novel agents targeting the AR signalling pathway under development, including more effective antiandrogens; inhibitors of CYP17, inhibitors of HSP90, inhibitors of histone deacetylases and inhibitors of tyrosine kinase inhibitors.

Geriatric oncology in Spain: survey results and analysis of the current situation.

INTRODUCTION: Geriatric oncology (GO) is a discipline that focuses on the management of elderly patients with cancer. The Spanish Society of Medical Oncology (SEOM) created a Working group dedicated to geriatric oncology in February 2016. OBJECTIVES: The main goal of this study was to describe the current situation in Spain regarding the management of elderly cancer patients through an online survey of medical oncologists. METHODS: A descriptive survey was sent to several hospitals by means of the SEOM website. A personal e-mail was also sent to SEOM members. RESULTS: Between March 2016 and April 2017, 154 answers were collected. Only 74 centers (48%) had a geriatrics department and a mere 21 (14%) medical oncology departments had a person dedicated to GO. The vast majority (n = 135; 88%) had the perception that the number of elderly patients with cancer seen in clinical practice had increased. Eighteen (12%) oncologists had specific protocols and geriatric scales were used at 55 (31%) centers. Almost all (92%) claimed to apply special management practices using specific tools. There was agreement that GO afforded certain potential advantages. Finally, 99% of the oncologists surveyed believed it and that training in GO had to be improved. CONCLUSIONS: From the nationwide survey promoted by the Spanish Geriatric Oncology Working Group on behalf of SEOM, we conclude that there is currently no defined care structure for elderly cancer patients. There is an increasing perception of the need for training in GO. This survey reflects a reality in which specific needs are perceived.

Geriatric oncology in Spain: survey results and analysis of the current situation

Introduction: Geriatric oncology (GO) is a discipline that focuses on the management of elderly patients with cancer. The Spanish Society of Medical Oncology (SEOM) created a Working group dedicated to geriatric oncology in February 2016. Objectives: The main goal of this study was to describe the current situation in Spain regarding the management of elderly cancer patients through an online survey of medical oncologists. Methods: A descriptive survey was sent to several hospitals by means of the SEOM website. A personal e-mail was also sent to SEOM members. Results: Between March 2016 and April 2017, 154 answers were collected. Only 74 centers (48%) had a geriatrics department and a mere 21 (14%) medical oncology departments had a person dedicated to GO. The vast majority (n = 135; 88%) had the perception that the number of elderly patients with cancer seen in clinical practice had increased. Eighteen (12%) oncologists had specific protocols and geriatric scales were used at 55 (31%) centers. Almost all (92%) claimed to apply special management practices using specific tools. There was agreement that GO afforded certain potential advantages. Finally, 99% of the oncologists surveyed believed it and that training in GO had to be improved. Conclusions: From the nationwide survey promoted by the Spanish Geriatric Oncology Working Group on behalf of SEOM, we conclude that there is currently no defined care structure for elderly cancer patients. There is an increasing perception of the need for training in GO. This survey reflects a reality in which specific needs are perceived

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Molecular biology of androgen-independent prostate cancer: the role of the androgen receptor pathway

Prostate cancer (PC) cells express the androgen receptor (AR) and need the presence of androgens to survive. Androgen suppression is the gold standard first-line therapy for metastatic disease. Almost all PC patients initially respond to hormonal therapy, but most of them gradually develop resistance to castration. There is evidence that these tumours that are considered castration-resistant continue to depend on AR signalling. Several mechanisms that enhance AR signalling in an androgen-depleted environment have been elucidated: (1) AR mutations that allow activation by low androgen levels or by other endogenous steroids, (2) AR amplification and/or overexpression, (3) increased local intracrine synthesis of androgens, (4) changes in AR cofactors and (5) cross-talk with cytokines and growth factors. Today, there are a number of novel agents targeting the AR signalling pathway under development, including more effective antiandrogens; inhibitors of CYP17, inhibitors of HSP90, inhibitors of histone deacetylases and inhibitors of tyrosine kinase inhibitors (AU)

No disponible