Validation of the CoVID-TE model as a tool to predict thrombosis, bleeding, and mortality in the oncology patient with Sars-Cov-2 infection: a study by the SEOM cancer and thrombosis group

Purpose The CoVID-TE model was developed with the aim of predicting venous thrombotic events (VTE) in cancer patients with Sars-Cov-2 infection. Moreover, it was capable of predicting hemorrhage and mortality 30 days following infection diagnosis. The model is pending validation. Methods/patients Multicenter retrospective study (10 centers). Adult patients with active oncologic disease/ antineoplastic therapy with Sars-Cov-2 infection hospitalized between March 1, 2020 and March 1. 2022 were recruited. The primary endpoint was to study the association between the risk categories of the CoVID-TE model and the occurrence of thrombosis using the Chi-Square test. Secondary endpoints were to demonstrate the association between these categories and the occurrence of post-diagnostic Sars-Cov-2 bleeding/ death events. The Kaplan–Meier method was also used to compare mortality by stratification. Results 263 patients were enrolled. 59.3% were men with a median age of 67 years. 73.8% had stage IV disease and lung cancer was the most prevalent tumor (24%). A total of 86.7% had an ECOG 0–2 and 77.9% were receiving active antineoplastic therapy. After a median follow-up of 6.83 months, the incidence of VTE, bleeding, and death 90 days after Sars-Cov-2 diagnosis in the low-risk group was 3.9% (95% CI 1.9–7.9), 4.5% (95% CI 2.3–8.6), and 52.5% (95% CI 45.2–59.7), respectively. For the high-risk group it was 6% (95% CI 2.6–13.2), 9.6% (95% CI 5.0–17.9), and 58.0% (95% CI 45.3–66.1). The Chi-square test for trends detected no statistically significant association between these variables (p > 0.05). Median survival in the low-risk group was 10.15 months (95% CI 3.84–16.46), while in the high-risk group it was 3.68 months (95% CI 0.0–7.79). The differences detected were not statistically significant (p = 0.375) (AU)

Efficacy and safety of chemotherapy in young patients with advanced gastroesophageal adenocarcinoma: data from the Spanish AGAMENON-SEOM registry.

BACKGROUND: Gastroesophageal adenocarcinoma in young adults (GCYA) counts for 10-15% of diagnoses. Previous studies have mainly focused on surgical outcomes in patients with resectable tumors; however, systemic therapy for advanced GCYA remains under-evaluated. This study aims to assess the efficacy-related outcomes and safety of first-line chemotherapy (CT) in younger versus older patients with advanced gastroesophageal adenocarcinoma. METHODS: Patients with advanced gastroesophageal adenocarcinoma from the AGAMENON-SEOM registry treated with first-line polychemotherapy between January 2008 and October 2022 were included. We compared clinicopathological features, therapies received, efficacy-related outcomes, and toxicity between individuals aged < and ≥ 45 years. RESULTS: Out of 3386 patients, 263 (7.8%) were < 45 years. Young patients exhibited a higher proportion of females affected, lower ECOG-PS ≥ 2, fewer comorbidities, and more aggressive disease-related features, such as higher proportion of diffuse subtype, signet-ring cells, plastic linitis, grade 3, peritoneal metastases and metastatic disease at diagnosis. They received more triple-agent combinations and underwent more surgeries in metastatic setting. No significant differences were observed between groups in overall response rate (53.1% vs. 52.3% in < and ≥ 45 years, respectively, p = 0.579), progression-free survival (6.1 vs. 6.83 months, p = 0.158) and overall survival (11.07 vs. 10.81 months, p = 0.82), even after adjusting for potential confounding factors. Grade 3-4 adverse events were comparable in both groups, although toxicity leading to treatment discontinuation was more frequent in older patients. CONCLUSIONS: In the AGAMENON-SEOM registry, younger patients with GCYA exhibited more aggressive clinicopathological features, and despite receiving more aggressive treatments, similar efficacy outcomes and toxicity profiles were achieved compared to their older counterparts. In the AGAMENON-SEOM registry, GEAC in < 45 years showed more aggressive clinicopathological features and, although treated with more intense first-line CT regimens, similar efficacy outcomes and toxicity were achieved compared to older patients.

Validation of the CoVID-TE model as a tool to predict thrombosis, bleeding, and mortality in the oncology patient with Sars-Cov-2 infection: a study by the SEOM cancer and thrombosis group.

PURPOSE: The CoVID-TE model was developed with the aim of predicting venous thrombotic events (VTE) in cancer patients with Sars-Cov-2 infection. Moreover, it was capable of predicting hemorrhage and mortality 30 days following infection diagnosis. The model is pending validation. METHODS/PATIENTS: Multicenter retrospective study (10 centers). Adult patients with active oncologic disease/ antineoplastic therapy with Sars-Cov-2 infection hospitalized between March 1, 2020 and March 1. 2022 were recruited. The primary endpoint was to study the association between the risk categories of the CoVID-TE model and the occurrence of thrombosis using the Chi-Square test. Secondary endpoints were to demonstrate the association between these categories and the occurrence of post-diagnostic Sars-Cov-2 bleeding/ death events. The Kaplan-Meier method was also used to compare mortality by stratification. RESULTS: 263 patients were enrolled. 59.3% were men with a median age of 67 years. 73.8% had stage IV disease and lung cancer was the most prevalent tumor (24%). A total of 86.7% had an ECOG 0-2 and 77.9% were receiving active antineoplastic therapy. After a median follow-up of 6.83 months, the incidence of VTE, bleeding, and death 90 days after Sars-Cov-2 diagnosis in the low-risk group was 3.9% (95% CI 1.9-7.9), 4.5% (95% CI 2.3-8.6), and 52.5% (95% CI 45.2-59.7), respectively. For the high-risk group it was 6% (95% CI 2.6-13.2), 9.6% (95% CI 5.0-17.9), and 58.0% (95% CI 45.3-66.1). The Chi-square test for trends detected no statistically significant association between these variables (p > 0.05). Median survival in the low-risk group was 10.15 months (95% CI 3.84-16.46), while in the high-risk group it was 3.68 months (95% CI 0.0-7.79). The differences detected were not statistically significant (p = 0.375). CONCLUSIONS: The data from our series does not validate of the CoVID-TE as a model to predict thrombosis, hemorrhage, or mortality in cancer patients with Sars-Cov-2 infection.

Immune checkpoint inhibitor-associated thrombosis in patients with bladder and kidney cancer: a study of the Spanish Society of Medical Oncology (SEOM) thrombosis and cancer group

Purpose Both venous and arterial thrombotic events (VTE/AT) can be associated with immune checkpoint inhibitors (ICI). However, there is a paucity of information apropos patients in routine clinical practice. Methods/patients Retrospective, multicenter study promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Individuals with kidney or bladder cancer who initiated ICI between 01/01/2015 and 12/31/2020 were recruited. Minimum follow-up was 6 months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT and secondary objectives included to analyze their impact on survival and identify variables predictive of VTE/AT. Results 210 patients with kidney cancer were enrolled. The incidence of VTE/AT during follow-up (median 13 months) was 5.7%. Median overall survival (OS) was relatively lower among subjects with VTE/AT (16 months, 95% CI 0.01–34.2 vs. 27 months, 95% CI 22.6–31.4; p = 0.43). Multivariate analysis failed to reveal predictive variables for developing VTE/ AT. 197 patients with bladder were enrolled. There was a 9.1% incidence rate of VTE/AT during follow-up (median 8 months). Median OS was somewhat higher in patients with VTE/AT (28 months, 95% CI 18.4–37.6 vs 25 months, 95% CI 20.7–29.3; p = 0.821). Serum albumin levels < 3.5 g/dl were predictive of VTE/ AT (p < 0.05). Conclusions There appears to be no association between developing VTE/AT and ICI use in patients with renal or bladder cancer. Serum albumin levels are a predictive factor in individuals with bladder cancer (AU)

Real-World Outcomes in Patients with Metastatic Colorectal Cancer in Spain: The RWD-ACROSS Study.

The retrospective, observational RWD-ACROSS study analyzed disease characteristics, systemic treatment, and survival in patients with metastatic colorectal cancer (mCRC) in Spain. In total, 2002 patients were enrolled (mean age 65.3 years; 62.7% male). Overall median overall survival (OS) was 26.72 months, and was longer in patients with left-sided tumors (28.85 vs. 21.04 months (right-sided tumors); p < 0.0001) and in patients receiving first-line anti-epidermal growth factor receptor (EGFR) treatment (31.21 vs. 26.75 (anti-vascular endothelial growth factor (VEGF) treatment) and 24.45 months (chemotherapy); p = 0.002). Overall median progression-free survival (PFS) was 10.72 months and was longer in patients with left-sided tumors (11.24 vs. 9.31 months (right-sided tumors); p < 0.0001), and in patients receiving either first-line anti-EGFR or anti-VEGF (12.13 and 12.00 vs. 8.98 months (chemotherapy); p < 0.001). PFS was longer with anti-VEGF treatment in patients with right-sided tumors and wild-type RAS (11.24 vs. 8.78 (anti-EGFR) and 7.83 months (chemotherapy); p = 0.025). Both anti-EGFR and anti-VEGF produced longer PFS in patients with left-sided tumors and wild-type RAS than chemotherapy alone (12.39 and 13.14 vs. 9.83 months; p = 0.011). In patients with left-sided tumors and mutant RAS, anti-VEGF produced a longer PFS than chemotherapy alone (12.36 vs. 9.34 months; p = 0.001). In Spain, wild-type RAS or left-sided mCRC tumors are predictive of longer survival times.

The Frequency of Specific KRAS Mutations, and Their Impact on Treatment Choice and Survival, in Patients With Metastatic Colorectal Cancer.

BACKGROUND: Patients with metastatic colorectal cancer (mCRC) and KRAS mutations have a poor prognosis, seemingly dependent on the location of the mutation. This multicenter, retrospective, cohort study assessed the frequency and prognostic value of specific KRAS mutation codon locations in mCRC patients, and survival outcomes in relation to treatment. MATERIALS AND METHODS: Data from mCRC patients treated in 10 Spanish hospitals between January 2011 and December 2015 were analyzed. The main objective was to investigate (1) the impact of KRAS mutation location on overall survival (OS), and (2) the effect of targeted treatment plus metastasectomy and primary tumor location on OS in patients with KRAS mutations. RESULTS: The KRAS mutation location was known for 337/2002 patients. Of these, 177 patients received chemotherapy only, 155 received bevacizumab plus chemotherapy, and 5 received anti-epidermal growth factor receptor therapy plus chemotherapy; 94 patients underwent surgery. The most frequent KRAS mutation locations were G12A (33.8%), G12D (21.4%), and G12V (21.4%). Compared with other locations, patients with a G12S mutation had the shortest median OS (10.3 [95% CI, 2.5-18.0] months). OS was longer in patients who underwent surgery versus those who did not, with a trend toward prolonged survival with bevacizumab (median OS 26.7 [95% CI, 21.8-31.7] months) versus chemotherapy alone (median OS 23.2 [95% CI, 19.4-27.0] months). CONCLUSION: These findings confirm that KRAS mutation location may predict survival outcomes in patients with mCRC, and suggest that pre-/post-operative bevacizumab plus metastasectomy provides survival benefits in patients with KRAS mutations.

Immune checkpoint inhibitor-associated thrombosis in patients with bladder and kidney cancer: a study of the Spanish Society of Medical Oncology (SEOM) thrombosis and cancer group.

PURPOSE: Both venous and arterial thrombotic events (VTE/AT) can be associated with immune checkpoint inhibitors (ICI). However, there is a paucity of information apropos patients in routine clinical practice. METHODS/PATIENTS: Retrospective, multicenter study promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Individuals with kidney or bladder cancer who initiated ICI between 01/01/2015 and 12/31/2020 were recruited. Minimum follow-up was 6 months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT and secondary objectives included to analyze their impact on survival and identify variables predictive of VTE/AT. RESULTS: 210 patients with kidney cancer were enrolled. The incidence of VTE/AT during follow-up (median 13 months) was 5.7%. Median overall survival (OS) was relatively lower among subjects with VTE/AT (16 months, 95% CI 0.01-34.2 vs. 27 months, 95% CI 22.6-31.4; p = 0.43). Multivariate analysis failed to reveal predictive variables for developing VTE/ AT. 197 patients with bladder were enrolled. There was a 9.1% incidence rate of VTE/AT during follow-up (median 8 months). Median OS was somewhat higher in patients with VTE/AT (28 months, 95% CI 18.4-37.6 vs 25 months, 95% CI 20.7-29.3; p = 0.821). Serum albumin levels < 3.5 g/dl were predictive of VTE/ AT (p < 0.05). CONCLUSIONS: There appears to be no association between developing VTE/AT and ICI use in patients with renal or bladder cancer. Serum albumin levels are a predictive factor in individuals with bladder cancer.

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

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

Immune checkpoint inhibitors-associated thrombosis in patients with lung cancer and melanoma: a study of the Spanish society of medical oncology (SEOM) thrombosis and cancer group

Purpose: Immune Checkpoint Inhibitors (ICI) can be associated with thrombotic events, both venous and arterial (VTE/AT). However, there is a paucity of information regarding patients in routine clinical practice.Methods/patientsRetrospective, multicenter study promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Patients with melanoma and lung cancer who initiated ICI between 01/01/2015 and 31/12/2019 were recruited. Minimum follow-up was 6 months (unless it was not possible because of death). The primary objective was to calculate the incidence of ICI-associated VTE/AT and the secondary objectives included to analyze its impact on survival and to identify predictor variables for VTE/AT.Results665 patients with lung cancer were enrolled. The incidence of VTE/AT during follow-up was 8.4%. Median overall survival (OS) was lower in the VTE/AT group (12 months 95% CI 4.84–19.16 vs. 19 months 95% CI 16.11–21.9; p = 0.0049). Neutrophil/lymphocyte ratio (NLR) and anemia upon initiation of IT, as well as a history of thrombosis between cancer diagnosis and the start of ICI, were predictive variables for developing of VTE/AT (p < 0.05). 291 patients with melanoma were enrolled. There was a 5.8% incidence rate of VTE/AT during follow-up. Median OS was lower in the VTE/AT group (10 months 95% CI 0.0–20.27 vs. 29 months 95% CI 19.58–36.42; p = 0.034). NLR and lactate dehydrogenase (LDH) at the beginning of ICI were predictor variables for VTE/AT (p < 0.05).ConclusionsICI increases the risk of VTE/AT in patients with lung cancer and melanoma, which impact OS. (AU)

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

BACKGROUND: Trastuzumab combined with cisplatin and fluoropyrimidines, either capecitabine or 5-fluorouracile (XP/FP), is the standard first-line treatment for advanced, HER2-positive, gastric cancer patients based on the ToGA trial. Despite the lack of phase III trials, many clinicians administer trastuzumab with alternative regimens. One meta-analysis suggests that substituting cisplatin for oxaliplatin might lead to greater efficacy and less toxicity. METHODS: 594 patients with HER2-positive gastroesophageal adenocarcinoma were recruited from the AGAMENON-SEOM registry. The objective was to evaluate the external validity of clinical trials with chemotherapy and trastuzumab. RESULTS: The regimens used in at least 5% of the patients were XP (27%), oxaliplatin and capecitabine (CAPOX) (26%), oxaliplatin and 5-fluorouracil (FOLFOX) (14%), FP (14%), triplet with anthracycline/docetaxel (7%), and carboplatin-FU (5%). Median exposure to trastuzumab was longer with FOLFOX (11.4 months, 95% CI, 9.1-21.0) versus ToGA regimens (7.5, 6.4-8.5), p < 0.001. Patients with HER2-IHC 3+ cancers had higher response rates than those with IHC 2+/FISH+, odds-ratio 1.97 (95% CI, 1.25-3.09). The results achieved with CAPOX-trastuzumab were comparable to those attained with ToGA regimens. FOLFOX-trastuzumab was superior to ToGA schemes in terms of overall survival (OS), with a greater magnitude of effect in IHC 2+/FISH+ tumors (HR 0.47, 0.24-0.92) compared with IHC 3+ (HR 0.69, 0.49-0.96), and in diffuse (HR 0.37, 0.20-0.69) versus intestinal-type tumors (HR 0.76, 0.54-1.06). CONCLUSION: We have updated the external validity of clinical trials with trastuzumab in first-line treatment of gastric cancer. Our data confirm the comparable outcomes of ToGA regimens and CAPOX-trastuzumab in clinical practice and point toward a possible benefit of FOLFOX-trastuzumab, contingent on the subtypes typically less sensitive to trastuzumab, to be confirmed in clinical trials.

Is advanced esophageal adenocarcinoma a distinct entity from intestinal subtype gastric cancer? Data from the AGAMENON-SEOM Registry.

BACKGROUND: Advanced esophageal adenocarcinoma (EAC) is generally treated similarly to advanced gastroesophageal junction (GEJ-AC) and gastric (GAC) adenocarcinomas, although GAC clinical trials rarely include EAC. This work sought to compare clinical characteristics and treatment outcomes of advanced EAC with those of GEJ-AC and GAC and examine prognostic factors. PATIENTS AND METHODS: Participants comprised patients with advanced EAC, intestinal GEJ-AC, and GAC treated with platin and fluoropyrimidine (plus trastuzumab when HER2 status was positive). Overall and progression-free survival were estimated using the Kaplan-Meier method. Cox proportional hazards regression gauged the prognostic value of the AGAMENON model. RESULTS: Between 2008 and 2019, 971 participants from the AGAMENON-SEOM registry were recruited at 35 centers. The sample included 67.3% GAC, 13.3% GEJ-AC, and 19.4% EAC. Pulmonary metastases were most common in EAC and peritoneal metastases in GAC. Median PFS and OS were 7.7 (95% CI 7.3-8.0) and 13.9 months (12.9-14.7). There was no difference in PFS or OS between HER2- and HER2+ tumors from the three locations (p > 0.05). Five covariates were found to be prognostic for the entire sample: ECOG-PS, histological grade, number of metastatic sites, NLR, and HER2+ tumors treated with trastuzumab. In EAC, the same variables were prognostic except for grade. The favorable prognosis for HER2+ cancers treated with trastuzumab was homogenous for all three subgroups (p = 0.351) and, after adjusting for the remaining covariates, no evidence supported primary tumor localization as a prognostic factor (p = 0.331). CONCLUSION: Our study supports the hypothesis that EAC exhibits clinicopathological characteristics, prognostic factors, and treatment outcomes comparable to intestinal GEJ-AC and GAC.

Surgery for metastases for esophageal-gastric cancer in the real world: Data from the AGAMENON national registry.

INTRODUCTION: The effect of surgery for metastases in patients with esophagogastric cancer is unknown, given the lack of randomized clinical trials; likewise, the criteria for selecting eligible patients remain to be determined. METHODS: This registry evaluates the results of patients with advanced adenocarcinoma of the stomach, distal esophagus, or gastro-esophageal junction from 32 centers. To assess selection criteria and prognostic factors, a state arrival extended Markov proportional hazards (PH) model was used. RESULTS: 1792 subjects were analyzed, 5% of whom (n = 92) underwent surgery for metastasis. The most common surgeries were peritoneal (29%), hepatic (24%), and distant lymph nodes (11%). Subjects chosen for metastasectomy had higher survival rates, HR 0.34 (95% CI, 0.06-0.80, p = 0.021). Patients who underwent surgery had a mOS since metastasectomy of 16.7 months (95% CI, 12.5-22.4). The 1- and 3-year relapse rates following R0 resection were 58% and 65%, respectively. Median time since R0 metastasectomy until relapse was 8.4 months (95% CI, 7.6-23.7). The 3-year OS after surgery was 30.6% (95% CI, 19.3-40.4). Duration of chemotherapy prior to surgery (months) increased mortality (HR 1.04 [95% CI, 1.01-1.07]), p = 0.009. The only significant interaction involved the use of anti-HER2 therapy. CONCLUSION: The AGAMENON registry suggests that subjects with limited metastatic disease, selected on a clinical basis, can benefit from early surgeries. Prospective trials are needed to confirm these data.