Tumor growth rate to assess therapy response to immune-based combinations for metastatic renal cell carcinoma

Background: Radiological response assessment is becoming challenging with novel immune-based combinations for metastatic renal cell carcinoma (mRCC). RECIST criteria appear not exhaustively adequate to capture the kinetics of treatment response, which is better reflected by tumor growth rate (TGR). We explored TGR changes during first-line treatments and its association with clinical outcomes in mRCC. Research design and methods: We retrospectively evaluated TGR in untreated patients undergoing pembrolizumab/axitinib (P/A) or tyrosine-kinase inhibitors (TKI). TGR was calculated at the first (TGR1, after 3 months) and the second (TGR2, after 6 months) evaluation, thus assessing the TGR2-TGR1 difference. Results: Thirty-three patients were included (P/A n = 15, TKIs n = 18). Volumes firstly decreased more rapidly with TKIs, and then more slowly. Volumes initially remained stable with P/A, quickly decreasing until the second evaluation. TGR1 was related to progression-free survival (PFS; p = 0.023) and overall survival (p = 0.046) with P/A. TGR2 was correlated with PFS in all patients (p = 0.025). Patients with higher velocity volume reduction appeared to have improved survival benefits than patients with lower velocity considering both treatments, but especially with P/A. Conclusion: Combining immunotherapy with TKIs has an important role in enhancing the rapidity of tumor shrinkage. A rapid disease volume reduction correlates with better OS and PFS

Integrated clinicopathologic and molecular analysis of endometrial carcinoma: Prognostic impact of the new ESGO-ESTRO-ESP endometrial cancer risk classification and proposal of histopathologic algorithm for its implementation in clinical practice

IntroductionThe European Society of Gynecologic Oncology/European Society of Radiation Therapy and Oncology/European Society of Pathology (ESGO/ESTRO/ESP) committee recently proposed a new risk stratification system for endometrial carcinoma (EC) patients that incorporates clinicopathologic and molecular features. The aim of the study is to compare the new ESGO/ESTRO/ESP risk classification system with the previous 2016 recommendations, evaluating the impact of molecular classification and defining a new algorithm for selecting cases for molecular analysis to assign the appropriate risk class.MethodsThe cohort included 211 consecutive EC patients. Immunohistochemistry and next-generation sequencing were used to assign molecular subgroups of EC: POLE mutant (POLE), mismatch repair deficient (MMRd), p53 mutant (p53abn), and no specific molecular profile (NSMP).ResultsImmuno-molecular analysis was successful in all cases, identifying the four molecular subgroups: 7.6% POLE, 32.2% MMRd, 20.9% p53abn, and 39.3% NSMP. The recent 2020 guidelines showed a 32.7% risk group change compared with the previous 2016 classification system: the reassignment is due to POLE mutations, abnormal p53 expression, and a better definition of lymphovascular space invasion. The 2020 system assigns more patients to lower-risk groups (42.2%) than the 2016 recommendation (25.6%). Considering the 2020 risk classification system that includes the difference between “unknown molecular classification” and “known,” the integration of molecular subgroups allowed 6.6% of patients to be recategorized into a different risk class. In addition, the use of the proposed algorithm based on histopathologic parameters would have resulted in a 62.6% reduction in molecular analysis, compared to applying molecular classification to all patients.ConclusionApplication of the new 2020 risk classification integrating clinicopathologic and molecular parameters provided more accurate identification of low-and high-risk patients, potentially allowing a more specific selection of patients for post-operative adjuvant therapy. The proposed histopathologic algorithm significantly decreases the number of tests needed and could be a promising tool for cost reduction without compromising prognostic stratification

Preliminary survey on the effects of ionizing radiations on Aspergillus spp. and on aflatoxin B1 contaminating maize grains

The aim of this research project was to evaluate the effects of ionizing radiations on Aspergillus spp. and on aflatoxin B1 levels contaminating maize grains. Eight samples of maize were irradiated by ionizing radiations respectively at doses of 3, 5, 7 and 10 kGy. The control samples showed a mean total viable mycetes count of 106 CFU/g and the mean levels of aflatoxin B1, detected by HPLC/FL, were 1212.8 median 1319 ppb. The effects of γ radiations on Aspergillus spp. produced a dose-dependent decrease in total moulds count and the appearance of some mutants. The AFB1 contamination was evaluated in samples irradiated at the 10 kGy dose, the maximum overall average absorbed radiation dose allowed by the European Community Directive. The results showed an increased AFB1 with mean level of 1975.8 ppb and median 1924.5 ppb. Key words: HPLC, Aspergillus spp., AFB1, γ rays, maize