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The microbiome is now regarded as one of the hallmarks of cancer and several strategies to modify the gut microbiota to improve immune checkpoint inhibitor (ICI) activity are being evaluated in clinical trials. Preliminary data regarding the upper gastro-intestinal microbiota indicated that Helicobacter pylori seropositivity was associated with a negative prognosis in patients amenable to ICI. In 97 patients with advanced melanoma treated with ICI, we assessed the impact of H. pylori on outcomes and microbiome composition. We performed H. pylori serology and profiled the fecal microbiome with metagenomics sequencing. Among the 97 patients, 22% were H. pylori positive (Pos). H. pylori Pos patients had a significantly shorter overall survival (p = .02) compared to H. pylori negative (Neg) patients. In addition, objective response rate and progression-free survival were decreased in H. pylori Pos patients. Metagenomics sequencing did not reveal any difference in diversity indexes between the H. pylori groups. At the taxa level, Eubacterium ventriosum, Mediterraneibacter (Ruminococcus) torques, and Dorea formicigenerans were increased in the H. pylori Pos group, while Alistipes finegoldii, Hungatella hathewayi and Blautia producta were over-represented in the H. pylori Neg group. In a second independent cohort of patients with NSCLC, diversity indexes were similar in both groups and Bacteroides xylanisolvens was increased in H. pylori Neg patients. Our results demonstrated that the negative impact of H. pylori on outcomes seem to be independent from the fecal microbiome composition. These findings warrant further validation and development of therapeutic strategies to eradicate H. pylori in immuno-oncology arena. [ABSTRACT FROM AUTHOR]

An early discrimination of survival probability is required for patients with diffuse large B cell lymphoma (DLBCL), which may identify patients that require other treatment options, for example clinical trials. To the best of our knowledge, the impact of interim evaluation with 18fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) has not yet been determined in this type of neoplasia. The aim of the present study was to determine the role of changes in metabolic tumor volume (MTV) between baseline and interim 18F-FDG PET/CT scans, following three courses of chemotherapy in order to predict complete response (CR) and overall survival (OS) in patients with DLBCL. Patients with previously untreated DLBCL who had received the standard 6-8 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone were included in the present study. A predictive model was constructed using changes in MTV and other clinical factors including age, gender, East Cooperative Oncology Group (ECOG) status, clinical stage, B symptoms, the presence of bulky disease and elevated lactate dehydrogenase levels, and data were analyzed using logistic regression analysis. In total, 50 patients with DLBCL were included in the present study. The majority of patients presented with stage III/IV disease (64%), B symptoms (72%) and bulky disease (58%). According to the International Prognostic Index score, 44% of patients were in the intermediate-high or high-risk categories for risk of relapse, and therefore considered to have poor prognosis. In total, ≥94% of patients achieving a decrease in total MTV had a 2-year OS rate of 95%, compared with the 58% OS rate of those with a suboptimal response. A multivariate model, including a change in MTV (a decrease of ≥94%), the ECOG performance status ≥2, a change in leukocyte counts and age, was used to predict CR. This model was used to define two groups according to the predicted probability of recurrence (cutoff, 0.69). The 2-year survival rates of the two groups were 95 and 59%, respectively. Analysis of changes in MTV in the interim 18F-FDG PET/CT revealed significant prognostic value for the prediction of CR and OS in patients with DLBCL. [ABSTRACT FROM AUTHOR]

Several approaches to manipulate the gut microbiome for improving the activity of cancer immune-checkpoint inhibitors (ICI) are currently under evaluation. Here, we show that oral supplementation with the polyphenol-rich berry camu-camu (CC; Myrciaria dubia) in mice shifted gut microbial composition, which translated into antitumor activity and a stronger anti-PD-1 response. We identified castalagin, an ellagitannin, as the active compound in CC. Oral administration of castalagin enriched for bacteria associated with efficient immunotherapeutic responses (Ruminococcaceae and Alistipes) and improved the CD8+/FOXP3+CD4+ ratio within the tumor microenvironment. Moreover, castalagin induced metabolic changes, resulting in an increase in taurine-conjugated bile acids. Oral supplementation of castalagin following fecal microbiota transplantation from ICI-refractory patients into mice supported anti-PD-1 activity. Finally, we found that castalagin binds to Ruminococcus bromii and promoted an anticancer response. Altogether, our results identify castalagin as a polyphenol that acts as a prebiotic to circumvent anti-PD-1 resistance., Significance: The polyphenol castalagin isolated from a berry has an antitumor effect through direct interactions with commensal bacteria, thus reprogramming the tumor microenvironment. In addition, in preclinical ICI-resistant models, castalagin reestablishes the efficacy of anti-PD-1. Together, these results provide a strong biological rationale to test castalagin as part of a clinical trial. This article is highlighted in the In This Issue feature, p. 873., (©2022 The Authors; Published by the American Association for Cancer Research.)

An early discrimination of survival probability is required for patients with diffuse large B cell lymphoma (DLBCL), which may identify patients that require other treatment options, for example clinical trials. To the best of our knowledge, the impact of interim evaluation with 18 fluorodeoxyglucose positron emission tomography-computed tomography ( 18 F-FDG PET/CT) has not yet been determined in this type of neoplasia. The aim of the present study was to determine the role of changes in metabolic tumor volume (MTV) between baseline and interim 18 F-FDG PET/CT scans, following three courses of chemotherapy in order to predict complete response (CR) and overall survival (OS) in patients with DLBCL. Patients with previously untreated DLBCL who had received the standard 6-8 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone were included in the present study. A predictive model was constructed using changes in MTV and other clinical factors including age, gender, East Cooperative Oncology Group (ECOG) status, clinical stage, B symptoms, the presence of bulky disease and elevated lactate dehydrogenase levels, and data were analyzed using logistic regression analysis. In total, 50 patients with DLBCL were included in the present study. The majority of patients presented with stage III/IV disease (64%), B symptoms (72%) and bulky disease (58%). According to the International Prognostic Index score, 44% of patients were in the intermediate-high or high-risk categories for risk of relapse, and therefore considered to have poor prognosis. In total, ≥94% of patients achieving a decrease in total MTV had a 2-year OS rate of 95%, compared with the 58% OS rate of those with a suboptimal response. A multivariate model, including a change in MTV (a decrease of ≥94%), the ECOG performance status ≥2, a change in leukocyte counts and age, was used to predict CR. This model was used to define two groups according to the predicted probability of recurrence (cutoff, 0.69). The 2-year survival rates of the two groups were 95 and 59%, respectively. Analysis of changes in MTV in the interim 18 F-FDG PET/CT revealed significant prognostic value for the prediction of CR and OS in patients with DLBCL.

Background: Available prognosis scores for patients with diffuse large B-cell lymphoma (DLBCL) included a limited number of patients ≥ 65 years of age, and most of them did not include comorbidities. Here, we propose a prognostic score for overall survival (OS) for this group of patients., Materials and Methods: Patients ≥ 65 years with DLBCL treated at a single national reference center were included. Clinical features including comorbidities and biochemical parameters were analyzed., Results: We included 141 patients. Response rate in the whole group was 77%. Based on multivariate analysis, the presence of the European Cooperative Oncology Group (ECOG) > 2, elevated levels of beta-2 microglobulin, bulky disease, and anemia (hemoglobin < 10 g/dL) had a significant effect on OS. These parameters were considered when computing the prognostic score, which identified three groups with differential survival: Low, intermediate, and high risk of death, with a probability of survival at 60 months of 80.05%, 55.5%, and 29.84%, respectively., Discussion: This score may select patients to optimize treatment. The presence of high levels of beta-2 microglobulin, bulky disease, and hemoglobin < 10 g/dL, and ECOG > 2 was associated with poor OS in elderly patients with DLBCL., (Copyright: © 2017 SecretarÍa de Salud.)

Blastic plasmacytoid dendritic cell neoplasm is a rare hematological malignancy derived from immature plasmacytoid dendritic cells. The tumor cells have an immature blastic appearance, and diagnosis is based on the expression of CD4, CD56 y CD123 in the absence of other lymphoid, natural killer, or myeloid antigens. The majority of affected individuals are older people with a mean age of 66 years. Male to female ratio is approximately 3:1. Common presentation includes cutaneous lesions followed by tumor dissemination. Treatment with conventional chemotherapy is ineffective and allogeneic hematopoietic stem cell transplantation is required to achieve remission. We report three male patients, aged 23, 27 and 51 years with the disease. All had multiple, infiltrated pink plaques and nodules on the skin of their face, neck and thorax, measuring 1 to 12 cm in diameter. All tumors were histologically characterized by a monotonous proliferation of medium size cells with blastic features. Tumor cells were positive for CD123, CD56, CD4 and CD7 in all cases. After a mean of follow-up of 14.6 months, one patient died of the disease, one patient is alive and the disease relapsed after 17 months of remission and one patient is alive with no evidence of the disease.