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.

Correction: Earl et al. Somatic Mutation Profiling in the Liquid Biopsy and Clinical Analysis of Hereditary and Familial Pancreatic Cancer Cases Reveals KRAS Negativity and a Longer Overall Survival. Cancers 2021, 13, 1612.

The authors wish to make the following corrections to this paper [...].

Somatic Mutation Profiling in the Liquid Biopsy and Clinical Analysis of Hereditary and Familial Pancreatic Cancer Cases Reveals KRAS Negativity and a Longer Overall Survival.

Pancreatic ductal adenocarcinoma (PDAC) presents many challenges in the clinic and there are many areas for improvement in diagnostics and patient management. The five-year survival rate is around 7.2% as the majority of patients present with advanced disease at diagnosis that is treatment resistant. Approximately 10-15% of PDAC cases have a hereditary basis or Familial Pancreatic Cancer (FPC). Here we demonstrate the use of circulating free DNA (cfDNA) in plasma as a prognostic biomarker in PDAC. The levels of cfDNA correlated with disease status, disease stage, and overall survival. Furthermore, we show for the first time via BEAMing that the majority of hereditary or familial PDAC cases (around 84%) are negative for a KRAS somatic mutation. In addition, KRAS mutation negative cases harbor somatic mutations in potentially druggable genes such as KIT, PDGFR, MET, BRAF, and PIK3CA that could be exploited in the clinic. Finally, familial or hereditary cases have a longer overall survival compared to sporadic cases (10.2 vs. 21.7 months, respectively). Currently, all patients are treated the same in the clinic with cytotoxic agents, although here we demonstrate that there are different subtypes of tumors at the genetic level that could pave the way to personalized treatment.

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.

Onset of ulcerative colitis and complete response during the treatment of a metastatic colon cancer: case report and literature review.

Colorectal cancer is a common cancer worldwide. Several risk factors have been described, such as age, lifestyle and family history. Inflammatory bowel diseases (IBD) are a well-recognized risk factor for the development of colorectal cancer. However, the onset of an IBD de novo in the context of the treatment of a colorectal neoplasia has not been reported before, except in the context of the treatment with immunocheckpoint inhibitors. Fifty-nine-years old man diagnosed with a metastatic colorectal cancer who received conventional treatment with chemotherapy and an antiangiogenic inhibitor. The patient had a complete response with the therapy after few cycles. Nevertheless, during the treatment, the patient presented with rectal bleeding, and was diagnosed with ulcerative colitis. Although the treatment was discontinued, tumoral complete remission is maintained. The relevance of this case lies in the concurrence of the onset of an autoimmune disease and a complete response of the malignancy. The concurrence of these events has been described previously only with immunotherapy. There are not cases reported involving chemotherapy and antiangiogenic drugs. Other causes of colitis were ruled out due to the unusual presentation of the case.

Second-line treatment in advanced gastric cancer: Data from the Spanish AGAMENON registry.

BACKGROUND: Second-line treatments boost overall survival in advanced gastric cancer (AGC). However, there is a paucity of information as to patterns of use and the results achieved in actual clinical practice. MATERIALS AND METHODS: The study population comprised patients with AGC in the AGAMENON registry who had received second-line. The objective was to describe the pattern of second-line therapies administered, progression-free survival following second-line (PFS-2), and post-progression survival since first-line (PPS). RESULTS: 2311 cases with 2066 progression events since first-line (89.3%) were recorded; 245 (10.6%) patients died during first-line treatment and 1326/2066 (64.1%) received a second-line. Median PFS-2 and PPS were 3.1 (95% CI, 2.9-3.3) and 5.8 months (5.5-6.3), respectively. The most widely used strategies were monoCT (56.9%), polyCT (15.0%), ramucirumab+CT (12.6%), platinum-reintroduction (8.3%), trastuzumab+CT (6.1%), and ramucirumab (1.1%). PFS-2/PPS medians gradually increased in monoCT, 2.6/5.1 months; polyCT 3.4/6.3 months; ramucirumab+CT, 4.1/6.5 months; platinum-reintroduction, 4.2/6.7 months, and for the HER2+ subgroup in particular, trastuzumab+CT, 5.2/11.7 months. Correlation between PFS since first-line and OS was moderate in the series as a whole (Kendall's τ = 0.613), lower in those subjects who received second-line (Kendall's τ = 0.539), especially with ramucirumab+CT (Kendall's τ = 0.413). CONCLUSION: This analysis reveals the diversity in second-line treatment for AGC, highlighting the effectiveness of paclitaxel-ramucirumab and, for a selected subgroup of patients, platinum reintroduction; both strategies endorsed by recent clinical guidelines.

Indoor Radon in EGFR- and BRAF-Mutated and ALK-Rearranged Non-Small-Cell Lung Cancer Patients.

BACKGROUND: Radon gas is the leading cause of lung cancer in the nonsmoking population. The World Health Organization (WHO) recommends indoor concentrations of < 100 Bq/m³. Several molecular alterations have been described in non-small-cell lung cancer (NSCLC), mainly in nonsmokers, with no risk factors identified. We studied the role of indoor radon in NSCLC patients harboring specific driver alterations. PATIENTS AND METHODS: We assessed the radon concentration from EGFR-, BRAF-mutated (m), and ALK-rearranged (r) NSCLC patients measured by an alpha-track detector placed in their homes between September 2014 and August 2015. Clinical characteristics were collected prospectively, and pathologic samples were reviewed retrospectively. RESULTS: Forty-eight patients were included (36 EGFRm, 10 ALKr, 2 BRAFm). Median radon concentration was 104 Bq/m³ (IQR 69-160) overall, and was 96 Bq/m³ (42-915) for EGFRm, 116 (64-852) for ALKr, and 125 for BRAFm, with no significant differences. Twenty-seven patients (56%) had indoor radon above WHO recommendations, 8 (80%) of 10 ALKr, 2 (100%) of 2 BRAFm, and 17 (47%) of 36 EGFRm. CONCLUSION: The median indoor radon concentration was above the WHO recommendations, with no differences between EGFR, ALK, and BRAF patients. Concentrations above the WHO recommendations were most common with ALKr and BRAFm. These findings should be validated in larger studies.

Survival in Advanced Esophagogastric Adenocarcinoma Improves With Use of Multiple Lines of Therapy: Results From an Analysis of More Than 500 Patients.

BACKGROUND: Although progress has been made in the molecular stratification of esophagogastric adenocarcinoma, the outlook for advanced disease remains poor. The present evaluation of over 500 patients treated at a single European high-volume tertiary center during a 6-year period gives important information on current and developing "real-world" treatment patterns and outcomes. RESULTS: The overall survival for the whole cohort was 11.5 months, with a range of treatments used in first-, second-, and third-line settings. Treatment with sequential lines of therapy was associated with better outcomes, although only 39% and 14% of patients subsequently received treatment in the second- and third-line setting, respectively. Treatment within a therapeutic clinical trial was associated with significantly improved survival. CONCLUSION: At present, a substantial proportion of patients with advanced esophagogastric adenocarcinoma will not proceed beyond first-line therapy, and for this group refinement of initial systemic therapies are required to improve outcomes. Although a number of established first- and second-line treatment options are now available, the therapeutic landscape of the disease continues to change, most notably in the application of immunotherapy and increasing interest in establishing evidence-based interventions in the third-line setting and beyond. A small but growing proportion of patients will benefit from sequential treatment approaches incorporating multiple lines of therapy, and improved selection of such patients will be a key challenge for clinicians moving forwards. Data such as these provide an overview of current treatment patterns and outcomes which can be used to inform planning of future research effectively within existing treatment frameworks.

A review of the empirical literature on the use of limpets Patella spp. (Mollusca: Gastropoda) as bioindicators of environmental quality.

The need to carry out monitoring programs for environmental pollution of coastal ecosystems makes it necessary to increase the number of indicator species in order to have a wide range of suitable organisms for most of the possible toxic substances and ways of exposure. With the purpose of analyzing the suitability of limpets (Patella spp.) for their use in biomonitoring programs, a literature review was performed on 88 cases found in the Web of Science online platform. The capacity of limpets to accumulate metals and hydrocarbons has been examined in several field studies. In most cases there is a clear relationship between body content of a pollutant in soft tissues of limpets and the corresponding environmental level. Likewise, different responses to pollutants have been reported in limpets, including induction of DNA damage, induction of metallothioneins, oxidative stress, decrease of Neutral Red retention or variations in heart rate. Regarding the study of changes in community structure, an uneven response to disturbances (e.g. oil spills, wastewater discharge) by species of the genus Patella has been documented. Moreover, generally limpets respond to pollutants similarly to, or even more effectively than, mussels; therefore, their inclusion as sentinel organisms in regional monitoring plans seems appropriate.

An Overview on the Sequential Treatment of Pancreatic Neuroendocrine Tumors (pNETs).

Patients suffering from pancreatic neuroendocrine tumors (pNETs) are now candidates to receive novel approved drugs that have demonstrated benefit in disease control rate and delay the time taken for tumor progression in Phase III clinical trials; for example, sunitinib, everolimus and lanreotide. Though pNETs represent a rare and heterogeneous disease, recent approaches are being taken to better understand the molecular pathways involved in carcinogenesis. Consequently, new treatment strategies are now available and others still under investigation show promising results. However, some questions around how to approach patients with pNETs are still unresolved, such as what the best sequence of treatments we can offer to each of our patients in the clinic at any time of their disease would be. Therapeutic decisions are, at the moment, guided by clinical judgment, based on different parameters coming from retrospective analysis and non-randomized clinical trials. However, advances in genomic research would lead to a more precise approach using therapeutic targets that would also allow the development of new agents, prognostic or predictive biomarkers and a better understanding of resistance mechanisms. The following article is a comprehensive review of the approved and investigational drugs in pNET, and highlights the current concerns about treatment sequencing, but also provides an update of some of the present and future efforts for an improvement in the therapeutic algorithm of the disease.

A comprehensive review of poorly differentiated neuroendocrine carcinomas (pdNECs): a niche to find novel opportunities.

Although grouped under the same name, neuroendocrine tumors comprise a heterogeneous family of neoplasms with a wide range of clinical and biological behaviors and responses to different treatment options. Most of the tumors derived from enterochromaffin cells are indolent or at least not as aggressive as epithelial tumors. However, a small percentage of these tumors have a poor prognosis and highly aggressive histology that results in a very short overall survival and scarce treatment options compared with well and moderately differentiated tumors. Patients with poorly differentiated neuroendocrine carcinomas barely exceed 6-8 months of survival. This particular poor risk subgroup of neuroendocrine tumors remains an unmet medical need and becomes a challenge in the daily clinical practice. A deeper knowledge of the biology and novel targeted agents might allow for future clinical development of novel agents in this setting. In this review we summarize the current background behind the management of poorly differentiated neuroendocrine carcinomas in daily clinical practice.