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Purpose: Molecular classification of endometrial cancer (EC) has emerged as a key approach to individualize therapy and define prognostic outcomes. This study aimed to implement the traditional ProMisE classification in a Brazilian population, compared with a molecular setting of ProMisE biomarkers, and evaluate its impact on patients' prognosis., Patient and Methods: A prospective cohort of 114 patients with primary EC treated at Barretos Cancer Hospital (BCH) between October 2020 and December 2022 was conducted. Pathology diagnosis, staging, treatment, and follow-up data were collected. The traditional ProMisE methodology was carried out by POLE hotspot sequencing and immunohistochemistry (IHC) for p53 and mismatch repair (MMR) proteins. We further evaluate the MMR and TP53 status by molecular approach, namely microsatellite instability (MSI) by PCR-based and TP53 mutation analysis by next-generation sequencing (NGS). The results of the 4 molecular groups in both methodologies were compared regarding agreement accuracy and survival outcomes., Results: Among the 114 cases, the traditional ProMisE groups were: POLE mut 15.8%, MMRd 28.1%, p53abn 27.2%, and no specific molecular profile (NSMP) 28.9%. Considering the molecular classification approach, we observed a POLE mut group of 15.8% , MSI group of 23.7%, TP53 mutation of 27.2%, and NSMP of 33.3%. The concordance rate of both approaches was 86.8% (99/114 cases) with an overall accuracy of 0.87. Importantly, both traditional and molecular ProMisE approaches were associated with significant distinct overall survival (OS) and progression-free survival (PFS) outcomes, with POLE mut patients exhibiting a better prognosis (93.8% OS, at 24 months), whereas the p53abn having a worse survival time (68.9% of OS, at 24 months)., Conclusion: We reported for the first time the Brazilian profile of the ProMisE classification of endometrial cancer and demonstrated the prognostic impact of the traditional and molecular ProMisE classification on patient outcomes., Competing Interests: Author DAPA works at the company Oncoclínicas&CO. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Andrade, Bonatelli, de Paula, Berardinelli, Teixeira, dos Reis, Barbin, Andrade, Aguiar, Hermoza, Hirai, Schmidt, Reis and dos Reis.)

Purpose: This scoping review aims to evaluate the evidence for stereotactic body radiotherapy (SBRT) boost as a potential alternative for brachytherapy (BCT) in treating cervical cancer., Material and Methods: A comprehensive literature search was conducted across multiple databases. Studies investigating SBRT boost in cervical cancer patients who were either contraindicated for or refused BCT were included. The review examined SBRT efficacy and safety., Results: Sixteen studies were included, encompassing prospective (n = 4) and retrospective cohort studies (n = 8), as well as phase I and II trials (n = 4). The most common SBRT boost dose was 25 Gray(Gy)/5 fractions (ranging from 18 to 40 Gy/3-5 fractions). Local control rates at 1-year, 3-year, and 5-year ranged from 86 % to 100 %, 78-92 %, and 81-92 %, respectively. Overall survival (OS) rates at 1-year, 3-year, and 5-year rates ranged from 49 % to 95 %, 50-77 %, and 50-69 %, respectively. Two studies reported a pathological complete response rate of 93 % and 94 % three months after the SBRT boost. Most studies reported low rates of late grade 3 or higher genitourinary (0-14 %) and gastrointestinal (0-26 %) toxicities. The overall incidence of rectovaginal fistulas ranged from 0 % to 13 %., Conclusion: This scoping review suggests SBRT boost as a promising alternative to selected cervical cancer patients who cannot receive BCT. The results indicate a high local control with acceptable toxicity profiles. However, further research is needed to define optimal SBRT boost parameters, identify patient selection criteria, and address knowledge gaps regarding long-term outcomes and cost-effectiveness., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Brazil is a middle-income country with inequalities in its healthcare system. The disparities between public and private services affect the diagnosis and treatment of patients with breast cancer. The aim of this study is to assess whether disease-free survival (DFS) and overall survival (OS) are different in public and private specialized centers., Patient and Methods: A retrospective cohort study with 1,545 breast cancer patients diagnosed from 2003 to 2011 at Barretos Cancer Hospital-BCH (public group, N = 1,408) and InORP Oncoclinicas (private group, N = 137) was conducted. A 1:1 propensity score matching (PSM) analysis was used to adjust the differences between the groups' characteristics (n = 137 in each group)., Results: The median age at diagnosis was 54.4 years. Estimated DFS rates at 1, 5, and 10 years were 96.0%, 71.8%, and 59.6%, respectively, at BCH and 97.8%, 86.9%, and 78%, respectively, at InORP (HR: 2.09; 95% confidence interval [CI], 1.41-3.10; p < 0.0001). Estimated OS rates at 1, 5, and 10 years were 98.1%, 78.5%, and 65.4%, respectively, at BCH and 99.3%, 94.5%, and 91.9%, respectively, at InORP (HR: 3.84; 95% CI, 2.16-6.82; p < 0.0001). After adjustment by PSM, DFS and OS results in 1, 3, and 5 years remained worse in the public service compared to the private service., Conclusion: Patients treated in a public center have worse DFS and OS after a follow-up period of more than 5 years. These results were corroborated after carrying out the PSM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Andrade, Veneziani, Paiva, Reis, Filho, Sanches, Barroso, Paz, Kons, Preto, Budib, Safro, Pinto, Bilibio and Souza.)

Background: Endometrial cancer is of increasing concern in several countries, including Brazil, in part because of an ageing population, declines in fertility, and the increasing prevalence of obesity. Although endometrial tumors had lagged behind other cancer types in terms of treatment improvements, molecular characterization of these tumors is paving the way for novel therapies and an expansion of the therapeutic arsenal. We aimed to help medical oncologists who manage patients with recurrent or metastatic endometrial cancer in the Brazilian healthcare setting., Methods: The panel, composed of 20 medical oncologists, convened in November 2021 to address 50 multiple-choice questions on molecular testing and treatment choices. We classified the level of agreement among panelists as (1) consensus (≥75% choosing the same answer), (2) majority vote (50% to <75%), or (3) less than majority vote (<50%)., Results: Consensus was present for 25 of the 50 questions, whereas majority vote was present for an additional 23 questions. Key recommendations include molecular testing for every patient with recurrent/metastatic endometrial cancer; choice of first-line treatment according to microsatellite instability and HER2, with the addition of programmed death ligand 1 (PD-L1) and hormone receptors (HRs) for second-line therapy; carboplatin and paclitaxel as the preferred option in first-line treatment of HER2-negative disease, with the addition of trastuzumab in HER2-positive disease; pembrolizumab plus lenvatinib as a key option in second line, regardless of HER2, PD-L1 or HRs; and various recommendations regarding treatment choice for patients with distinct comorbidities., Conclusion: Despite the existing gaps in the current literature, the vast majority of issues addressed by the panel provided a level of agreement sufficient to inform clinical practice in Brazil and in other countries with similar healthcare environments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 de Andrade, Guimarães, de Melo, Nogueira-Rodrigues, Gomes, Scaranti, Maia, Morelle, Santos, Souza, de Freitas, Callegaro Filho, Paulino, Júnior, Pimenta, Santos, de Almeida, Souza, Cabral and Maluf.)

Cervical cancer (CC) is a worldwide problem, especially in low- and middle-income countries, where patients are often diagnosed with locally advanced disease. Until recently, all chemotherapy drugs achieved low ORR and 12-month overall survival (12- month OS) for advanced CC after failure for platinum compounds. Advances in systemic therapy with immunotherapy, targeted therapy, and antibody-drug conjugates (ADC) have leveraged the 12-month OS limit. Recently, immunotherapy (pembrolizumab) has become the standard of care in first-line advanced CC combined with platinum and taxane and in second-line after platinum doublet failure., Competing Interests: Conflict of interest The authors declare no potential., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: A nationwide lockdown was enforced in Brazil starting in March 2020 because of the COVID-19 pandemic when cancer screening activities were reduced. In this study, we evaluated the impact of the COVID-19 pandemic on breast cancer (BC) diagnosis., Methods: We extracted data from the medical records of patients age older than 18 years who were diagnosed with BC and started treatment or follow-up in private oncology institutions in Brazil between 2018 and 2021. The primary objective was to compare the stage distribution during the COVID-19 pandemic (2020-2021) with a historical prepandemic control cohort (2018-2019). Early BC was defined as stage I-II and advanced disease as stage IV., Results: We collected data for 11,753 patients with an initial diagnosis of BC, with 6,493 patients in the pandemic (2020-2021) and 5,260 patients in the prepandemic period (2018-2019). We observed a lower prevalence of early-stage BC (63.6% v 68.4%) and a higher prevalence of advanced-stage BC (16.9 v 12.7%), after the onset of the pandemic (both P < .01). This pattern was similar for both estrogen receptor-positive/human epidermal growth factor receptor 2-negative and human epidermal growth factor receptor 2-positive tumors: significantly decreased in the early stage from 69% to 67% and 68% to 58%, respectively, and a considerable increase in advanced-stage disease from 13% to 15% and 13% to 20%, respectively. For triple-negative BC, there was a significantly higher percentage of patients with advanced-stage disease during the pandemic (17% v 11%). Overall, age 50 years or older and postmenopausal status were associated with a greater risk of advanced stage at diagnosis during the pandemic period., Conclusion: We observed a substantial increase in the number of cases of advanced-stage BC in Brazil during the COVID-19 pandemic.

Cervical cancer remains a leading cause of morbidity and mortality amongst females in Latin America (LATAM). Cervical cancer is a preventable disease and HPV vaccination is a main key strategy towards its elimination. This study analyzes HPV vaccine implementation current status and the main barriers to achieve adequate coverage in the region. Data from the nineteen sovereign states of LATAM (comprised of all Portuguese and Spanish-speaking nations located south of the United States) were collected, including year of HPV vaccine implementation, gender and age targets, the number of doses included in the public program and coverage by dose. Sixteen out of the 19 evaluated countries have already implemented HPV vaccination programs. However, despite its proven efficacy and safety, HPV vaccine uptake in LATAM has been lower than expected. There is an evident decline in adhesion, mainly regarding the second dose. Several reasons are probably involved, of note: limited knowledge of HPV and HPV vaccine, misguided safety concerns, high cost, cultural barriers, and the Covid19 pandemic. Proper strategies to overcome these barriers are needed to ensure successful uptake. Effective policies are: adopting the one dose schedule, delivering the vaccine on both health center and schools, and advising health professionals to recommend the vaccine. Further research regarding HPV vaccine hesitancy in Latin America is needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nogueira-Rodrigues, Flores, Macedo Neto, Braga, Vieira, Sousa-Lima, de Andrade, Machado and Guimarães.)

Background: The molecular profile of endometrial cancer has become an important tool in determining patient prognosis and their optimal adjuvant treatment. In addition to The Cancer Genome Atlas (TCGA), simpler tools have been developed, such as the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE). We attempted to determine a genetic signature to build a recurrence risk score in patients diagnosed with low- and intermediate-risk endometrial cancer., Methods: A case-control study was conducted. The eligible patients were women diagnosed with recurrence low- and intermediate-risk endometrial cancer between January 2009 and December 2014 at a single institution; the recurrence patients were matched to two nonrecurrence patients with the same diagnosis by age and surgical staging. Following RNA isolation of 51 cases, 17 recurrence and 34 nonrecurrence patients, the expression profile was determined using the nCounter ® PanCancer Pathways Panel , which contains 770 genes., Results: The expression profile was successfully characterized in 49/51 (96.1%) cases. We identified 12 genes differentially expressed between the recurrence and nonrecurrence groups. The ROC curve for each gene was generated, and all had AUCs higher than 0.7. After backward stepwise logistic regression, four genes were highlighted: FN1, DUSP4, LEF1, and SMAD9 . The recurrence risk score was calculated, leading to a ROC curve of the 4-gene model with an AUC of 0.93, sensitivity of 100%, and specificity of 72.7%., Conclusion: We identified a four-gene signature that may be associated with recurrence in patients with low- and intermediate-risk endometrial cancer. This finding suggests a new prognostic factor in this poorly explored group of patients with endometrial cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 de Andrade, da Silva, Laus, de Lima, Berardinelli, da Silva, Matsushita, Bonatelli, da Silva, Evangelista, Carvalho, Reis and dos Reis.)

The current study aimed to evaluate the accuracy of diffusion‑weighted imaging and morphological aspects at 3 Tesla (T) and 1.5T MRI for diagnosing metastatic lymph nodes (LN) in cervical cancer. A retrospective study was conducted at the Barretos Cancer Hospital. A total of 45 patients with cervical cancer who underwent MRI examination and pelvic and/or para‑aortic lymphadenectomy as part of surgical procedure were included. Data regarding LN images included size (short‑axis diameters), morphology (usual, rounded or amorphous), appearance (homogeneous or heterogeneous), limits (regular, irregular or imprecise), presence or absence of necrosis, diffusion (normal or greater restriction than expected for normal tissue) and aspect (suspected, undetermined or normal). These findings were compared with histopathological results. According to histology results, among the 45 patients, 14 (31.1%) LNs were tested positive for metastasis and 31 (68.9%) LNs were tested negative. A total of 41 metastatic positive LNs were detected from a total of 976 resected nodes. Twelve patients from the 45 (26.7%) had LN classified as metastatic by histology and suspected by MRI, 26 (57.8%) as negative in both evaluations, 2 (4.4%) as positive by histology and negative by MRI and five (11.1%) as negative by histology and positive by MRI. Based on these results, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were 85.7, 83.9, 70.6, 92.9 and 84.4%, respectively. The Cohen's κ test exposed a general outcome of 0.657 (P<0.05), demonstrating that the two variables (histology and MRI) have substantial concordance. The κ test results between histological and MRI data for paraaortic and pelvic LNs were found to be 1 and 0.657, respectively. Finally, short axis >10 mm, T2 hypointensity, rounded morphology and greater restriction than expected for normal tissues are the four most common MRI findings associated with metastatic LN. The concordance between MRI and histology was substantial, indicating that this method using MRI for diagnosing suspected LN metastasis is reliable. The results of the current study revealed that the most important aspects to be evaluated in MRI include: Short axis >10 mm, T2 hypointensity, rounded morphology and greater restriction than expected for normal tissues. If these four characteristics are present in MRI, histological evaluation is likely to reveal positive lymph node metastasis.

Objective: To evaluate the difference between early and delayed removal of indwelling urinary catheter after radical hysterectomy (RH) or radical trachelectomy (RT)., Methods: An ambispective study was conducted in early-stage cervical cancer patients who underwent RH or RT. Delayed indwelling urinary catheter removal occurred on a postoperative day (POD) 7 in the retrospective group (January 2012-November 2013), and early removal occurred on POD 1 in the prospective group (May 2014-June 2017). The postvoid residual (PVR) test was performed after indwelling catheter removal in both groups., Results: Our sample included 47 patients in the delayed group and 48 in the early one. There was no difference in age, body mass index, tumor size, histology, stage, surgical approach, and intraoperative and postoperative complications. Indwelling urinary catheter reinsertion was needed in 16 (34%) patients in the delayed group and 12 (25%) in the early group (P = .37), with no statistical difference between the median PVR volumes -82.5 and 45 mL (P = .06), respectively. Seven (14.9%) patients in the delayed group presented with 30-day urinary tract infection vs two (4.2%) in the early group (P = .09)., Conclusions: Early indwelling urinary catheter removal, in regard to the rate of catheter reinsertion and PVR volume, does not differ from delayed removal., (© 2020 Wiley Periodicals LLC.)

Purpose: In Brazil, the available cancer registries are deficient in number and quality and, hence, little information is known regarding sociodemographic, clinicopathological characteristics, treatment patterns, and outcomes of breast cancer (BC) patients. We performed the AMAZONA III/ GBECAM 0115 study and in this analysis, we describe patients' characteristics at diagnosis and their association with health insurance type., Methods: This is a prospective cohort study developed in 23 sites in Brazil including women with newly diagnosed invasive BC from January 2016 to March 2018. In order to compare healthcare insurance type, we considered patients who were treated under the Brazilian public health system as publicly insured, and women who had private insurance or paid for their treatment as privately insured., Results: A total of 2950 patients were included in the study. Median age at diagnosis was 53.9 years; 63.1% were publicly insured. The majority of patients (68.6%) had stage II-III breast cancer and ductal carcinoma histology (80.9%). The most common breast cancer subtype was luminal A-like (48.0%) followed by luminal B-HER2 positive-like (17.0%) and triple-negative (15.6%). Luminal A was more frequent in private (53.7% vs. 44.2%, p < .0001) than public, whereas Luminal B HER2-positive (19.2% vs. 14.2%, p = 0.0012) and HER2-positive (8.8% vs. 5.1%, p = 0.0009) were more common in patients with public health system coverage. Only 34% of patients were diagnosed by screening exams. Privately insured patients were more frequently diagnosed with stage I disease when compared to publicly insured patients; publicly insured patients had more stage III (33.5% vs. 14.7%; p-value < 0.0001) disease than privately insured ones. Breast cancer was detected by symptoms more frequently in publicly than in privately insured patients (74.2% vs 25.8%, respectively; p-value < 0.0001)., Conclusions: Patients with public health coverage were diagnosed with symptomatic disease, later stages and more aggressive subtypes when compared to privately insured patients.

Background: Endometrial cancer presents well-defined risk factors: myometrial invasion, histological subtype, tumor grade, lymphovascular space invasion (LVSI). Some low and intermediate-risk endometrioid endometrial cancer patients exhibited unexpected outcomes. This study aimed to investigate other clinical-pathological factors that might influence the recurrence rates of patients diagnosed with low and intermediate-risk endometrioid endometrial cancer., Methods: A case-control study from a cohort retrospective of 196 patients diagnosed with low and intermediate-risk endometrioid endometrial cancer at a single institution from 2009 to 2014 was conducted. Medical records were reviewed to compare clinical (race, smoking, menopause age, body mass index) and pathological (endometrioid vs endometrioid with squamous differentiation, tumor differentiation grade, tumor location, endocervical invasion, LVSI) features of patients with recurrence (case) and without recurrence (control) of disease. Three controls for each case were matched for age and staging., Results: Twenty-one patients with recurrence were found (10.7%), of which 14 were stage IA, and 7 were stage IB. In accordance, 63 patients without recurrence were selected as controls. There were no significant differences in any clinical characteristics between cases and controls. Among pathological variables, presence of squamous differentiation (28.6% vs. 4.8%, p = 0.007), tumor differentiation grade 2 or 3 (57.1% vs. 30.2%, p = 0.037) and presence of endocervical invasion (28.6% vs. 12.7%, p = 0.103) were associated with disease recurrence on a univariate analysis. On multivariable analysis, only squamous differentiation was a significant risk factor for recurrence (p = 0.031)., Conclusion: Our data suggest that squamous differentiation may be an adverse prognostic factor in patients with low and intermediate-risk endometrioid endometrial cancer, that showed a 5.6-fold increased risk for recurrence., Competing Interests: The authors have declared that no competing interests exist.

Objective:  To describe a series of cases of ovarian Sertoli-Leydig cell tumors (SLCTs)., Methods:  Retrospective review of 12 cases of SLCT treated at the Hospital do Câncer de Barretos, Barretos, state of São Paulo, Brazil, between October 2009 and August 2017., Results:  The median age of the patients was 31 years old (15-71 years old). A total of 9 patients (75.0%) presented symptoms: 8 (66.7%) presented with abdominal pain, 5 (41.7%) presented with abdominal enlargement, 2 (16.7%) presented with virilizing signs, 2 (16.7%) presented with abnormal uterine bleeding, 1 (8.3%) presented with dyspareunia, and 1 (8.3%) presented with weight loss. The median preoperative lactate dehydrogenase (LDH) was 504.5 U/L (138-569 U/L), alpha-fetoprotein (AFP) was 2.0 ng/ml (1.1-11.3 ng/ml), human chorionic gonadotropin (β-hCG) was 0.6 mUI/ml (0.0-2.3 mUI/ml), carcinoembryonic antigen (CEA) was 0.9 ng/ml (0.7-3.4 ng/ml), and cancer antigen 125 (CA-125) was 26.0 U/ml (19.1-147.0 U/ml). All of the tumors were unilateral and surgically treated. Lymphadenectomy was performed in 3 (25.0%) patients, but none of the three patients submitted to lymphadenectomy presented lymph node involvement. In the anatomopathological exam, 1 (8.3%) tumor was well-differentiated, 8 (66.7%) were moderately differentiated, and 3 (25.0%) were poorly differentiated. A total of 5 (55.6%) tumors were solid-cystic, 2 (22.2%) were purely cystic, 1 (11.1%) was cystic with vegetations, and 1 (11.1%) was purely solid, but for 3 patients this information was not available. The median lesion size was 14.2 cm (3.2-23.5 cm). All of the tumors were at stage IA of the 2014 classification of the International Federation of Gynecology and Obstetrics (FIGO). A total of 2 (16.7%) patients received adjuvant treatment; 1 of them underwent 3 cycles of paclitaxel and carboplatin every 21 days, and the other underwent 4 cycles of ifosfamide, cisplatin and etoposide every 21 days. None of all of the patients had recurrence, and one death related to complications after surgical staging occurred., Conclusion:  Abdominal pain was the most frequent presentation. There was no ultrasonographic pattern. All of the SLCTs were at stage IA, and most of them were moderately differentiated. Relapses did not occur, but one death related to the surgical staging occurred., Competing Interests: The authors have no conflicts of interests to declare., (Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.)

Background/aims: Gastric cancer (GC) is a significant global health issue with high incidence rates and poor prognoses, ranking among the top prevalent cancers worldwide. Due to undesirable side effects and drug resistance, there is a pressing need for the development of novel therapeutic strategies. Understanding the interconnectedness of the JAK2/STAT3/mTOR/PI3K pathway in tumorigenesis and the role of Astaxanthin (ASX), a red ketocarotenoid member of xanthophylls and potent antioxidant and anti-tumor activity, can be effective for cancer treatments. This study aimed to investigate the effect of ASX-loaded nanoparticles on the survival of MKN-45 GC cells and the expression of JAK2/STAT3/mTOR/PI3K, offering insights into potential targeted therapies for GC. Methods: The growth status and survival rate of MKN-45 GC cell lines were determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide(MTT) assay, and the optimal IC50 concentration of ASX, PLGA, and ASX + PLGA was estimated. Also, the clonogenic assay was performed to determine the reproductive power and colony formation of under-treatment cells. Apoptosis and necroptosis of cells were evaluated using acridine orange (AO) staining. The western blot assessed the protein's level of expression and intensity (JAK2/STAT3/mTOR/PI3K). SPSS version 16 software was used for statistical analysis, P-value was considered lower than 0.05. Results: Based on the results, increasing concentrations of ASX and ASX + PLGA led to a decrease in the viability of MKN-45 cells compared to the control group (P < 0.001). This value was lower for cells treated with ASX + PLGA (P = 0.003). The IC50 values for each of the studied groups (ASX, ASX + PLGA, and PLGA) were 81.45 µg/ml, 51.45 µg/ml, and 3.383 mg/ml, respectively. The levels of expression and intensity of JAK2, STAT3, and mTOR proteins in the Western blotting analysis under ASX + PLGA treatment increased compared to the control group. Conversely, the levels of expression and intensity of P-JAK2, P-STAT3, and P-mTOR proteins in the ASX + PLGA treatment group decreased by 41%, 34%, 37%, and 43%, respectively, compared to the control group. Protein expression levels and intensities of JAK2, STAT3, and mTOR significantly increased when treated with PLGA, ASX, and ASX + PLGA compared to the control group (P < 0.001). Conclusions: The encapsulation of ASX in PLGA nanoparticles enhances drug stability, enables targeted delivery, and allows for sustained release. This study highlights the therapeutic potential of ASX-loaded nanoparticles in targeting JAK2/STAT3/mTOR/PI3K pathways in GC treatment. Further research is needed to understand the mechanisms and clinical applications of this novel immunotherapy strategy. [ABSTRACT FROM AUTHOR]

Research works suggested the role of long non-coding RNAs (lncRNAs) in pathogenesis of clear cell renal cell carcinoma (ccRCC). lncRNA HAGLR is studied in several malignancies, but not in ccRCC. From The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) dataset, we analyzed molecular alterations of HAGLR and constructed a competitive endogenous RNA (ceRNA) network with related miRNAs and mRNAs. Gene Ontology analysis was done to identify important pathways enriched with HAGLR recovered mRNAs. Clinical importance of HAGLR and related mRNAs was assessed and, the impact of selected mRNA-encoding genes on tumor immune infiltration was studied using TIMER. HAGLR expression was reduced in ccRCC than in normal kidneys, and correlated significantly with gene promoter methylation. Low HAGLR level in tumors showed diagnostic potency, and was associated with clinicopathological parameters (stage/grade/metastasis) and poor patient survival. The HAGLR-associated ceRNA network constituted 13 miRNAs and 23 mRNAs differentially expressed in the TCGA-KIRC dataset. From HAGLR recovered mRNA-encoding genes, we developed a 5-gene (PAQR5, ARHGAP24, HABP4, PDLIM5, and RPS6KA2) prognostic signature in the training dataset and validated it in testing as well as entire datasets. The expression level of signature genes showed negative correlation with tumor infiltration of immune cells having adverse impact on ccRCC prognosis and also with tumor derived chemokines facilitating the infiltration. In conclusion, HAGLR seemed to play a tumor suppressive role in ccRCC. HAGLR and associated gene signature may have implementation in improving existing prognostic measure and developing effective immunotherapeutic strategies for ccRCC. [ABSTRACT FROM AUTHOR]

The FIGO scheme is currently applied for tumor grading of endometrioid adenocarcinoma. The current report presents a series of ten cases of endometrioid carcinomas that when applying the FIGO grading does not fully convey the true biological nature of the disease. The squamous component of these tumors is malignant; it constitutes the predominant invasive component, and it often metastasizes to unconventional sites. Half of the cohort developed distant disease recurrence within 2 years, even those with early-stage disease. Somatic mutations were analyzed, targeting 101 genes in all ten cases, and mutations in PTEN, MMR, PIK3CA, ATM, RB1, and TP53 genes were detected, often multiple mutations in the same case. None of the cases revealed unique molecular signatures or previously unreported gene mutations. Immunohistochemical staining for beta-catenin showed aberrant nuclear staining in eight of ten cases and remaining two showed cytoplasmic and membranous staining. Aggressive behavior and unusual sites of metastases are observed in this series even in low-grade tumor. The FIGO grading on smaller samples may be deceptive for these cases. Even if FIGO is applied, the pathology report should emphasize the malignant squamous component and its potential significance so that the gynecologic oncology team can formulate appropriate adjuvant treatment upfront. This case series argues that this histology should be regarded as a high-grade endometrioid carcinoma and can show unusual metastatic patterns. Further research is needed with more cases within this histologic subtype to guide recommendations on adjuvant therapies for this aggressive tumor type., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In Brazil, data on the management of triple negative breast cancer (TNBC) as well as the burden of the disease in terms of health care resources utilization (HCRU) are scarce. To characterize the treatment patterns and HCRU associated with the management of Brazilian TNBC patients from the perspective of the private healthcare setting. Patients with at least one claim related to ICD-10 C50 from January 2012 until December 2017, and at least one claim for breast cancer treatment were assessed from a private claims database and classified as early and locally advanced, or metastatic. All patients with hormone and/or targeted therapy were excluded. Three thousand and four patients were identified, of which 82.8% were diagnosed in early and locally advanced stages. For early and locally advanced TNBC patients, 75.3% were treated in an adjuvant setting, mainly with anthracycline regimes. For mTNBC patients, bevacizumab regimens were the main treatment prescribed. More than 48% of mTNBC patients were switched to a second line of treatment. HCRU was higher for mTNBC patients when compared to early and locally advanced patients, with higher costs for metastatic disease management. The treatment setting has little influence on the HCRU pattern or the cost of disease management. The highest burden of disease was observed for metastatic management. [ABSTRACT FROM AUTHOR]

Introduction and Hypothesis: Many patients develop bladder symptoms after radical hysterectomy. This study compared urinary outcomes following radical hysterectomy based on trial of void (TOV) timing (pre-discharge TOV versus post-discharge TOV)., Methods: A retrospective non-inferiority study of patients at two academic tertiary referral centers who underwent radical hysterectomy between January 2010 and January 2020 was carried out. Patients were stratified according to timing of postoperative TOV: either pre-discharge or post-discharge from the hospital. Short-term urinary outcomes (including passing TOV, representation with retention) and long-term de novo urinary dysfunction (defined as irritative voiding symptoms, urgency, frequency, nocturia, stress or urgency incontinence, neurogenic bladder, and/or urinary retention) were extracted from the medical record. We hypothesized that the proportion of patients who failed pre-discharge TOV would be within a 15% non-inferiority margin of post-discharge TOV., Results: A total of 198 patients underwent radical hysterectomy for cervical (118 out of 198; 59.6%), uterine (36 out of 198; 18.2%), and ovarian (29 out of 198; 14.6%) cancer. One hundred and nineteen patients (119 out of 198, 60.1%) underwent pre-discharge TOV, of whom 14 out of 119 (11.8%) failed. Of the post-discharge TOV patients (79 out of 198, 39.9%), 5 out of 79 (6.3%) failed. The proportion of patients who failed a pre-discharge TOV was within the non-inferiority margin (5.4% difference, p = 0.23). A greater proportion of patients in the post-discharge TOV group developed long-term de novo urinary dysfunction (27.2% difference, p = 0.005). Median time to diagnosis of de novo urinary dysfunction was 0.5 years (range 0-9) in the pre-discharge TOV group versus 1.0 year (range 0-6) in the post-discharge TOV group (p > 0.05)., Conclusions: In this study, pre-discharge TOV had non-inferior short-term outcomes and improved long-term outcomes., (© 2024. The International Urogynecological Association.)

Background: Acral melanoma is rare and associated with a worse prognosis compared to cutaneous melanoma in other locations. Despite this, few studies have focused on the prognosis of acral melanoma, particularly in patients with initial clinical stage. The aim of this study was to assess the impact of clinical and histopathological characteristics on the disease‐free survival (DFS) of stage I‐II patients. Methods: We analyzed 154 stage I‐II acral melanoma cases, all of whom underwent a review of the histopathological and clinical parameters. Patients were divided into groups based on the presence or absence of disease recurrence within 5 years. We used Cox proportional regression to analyze independent risk factors and computed DFS curves using the Kaplan–Meier method. Results: Within 5 years, 27.9% of patients experienced disease recurrence, with 90.4% occurring during the first 3 years. Univariate and multivariate analyses did not identify any clinical parameters with a significant influence on DFS. The DFS rate at 5 years was 72.7%. The median duration of disease recurrence after the initial diagnosis was 21 months. However, Breslow thickness, presence of ulceration, >3 mitosis/mm2, presence of tumor‐infiltrating lymphocytes (TIL), and perineural invasion were significantly associated with a decrease in time to first recurrence. Conclusions: Despite the favorable prognosis of stage I‐II acral melanoma compared with advance stage, clinical and histopathological characteristics can impact prognosis. In addition to Breslow thickness and ulceration, attention should be paid to mitotic rate, presence of TIL, and perineural invasion to optimize follow‐up of acral melanoma patients diagnosed in the initial clinical stage. [ABSTRACT FROM AUTHOR]

Background: Brazil is a middle-income country with inequalities in its healthcare system. The disparities between public and private services affect the diagnosis and treatment of patients with breast cancer. The aim of this study is to assess whether disease-free survival (DFS) and overall survival (OS) are different in public and private specialized centers. Patient and methods: A retrospective cohort study with 1,545 breast cancer patients diagnosed from 2003 to 2011 at Barretos Cancer Hospital--BCH (public group, N = 1,408) and InORP Oncoclinicas (private group, N = 137) was conducted. A 1:1 propensity score matching (PSM) analysis was used to adjust the differences between the groups' characteristics (n = 137 in each group). Results: The median age at diagnosis was 54.4 years. Estimated DFS rates at 1, 5, and 10 years were 96.0%, 71.8%, and 59.6%, respectively, at BCH and 97.8%, 86.9%, and 78%, respectively, at InORP (HR: 2.09; 95% confidence interval [CI], 1.41-3.10; p < 0.0001). Estimated OS rates at 1, 5, and 10 years were 98.1%, 78.5%, and 65.4%, respectively, at BCH and 99.3%, 94.5%, and 91.9%, respectively, at InORP (HR: 3.84; 95% CI, 2.16-6.82; p < 0.0001). After adjustment by PSM, DFS and OS results in 1, 3, and 5 years remained worse in the public service compared to the private service. Conclusion: Patients treated in a public center have worse DFS and OS after a follow-up period of more than 5 years. These results were corroborated after carrying out the PSM. [ABSTRACT FROM AUTHOR]

Background: Some studies reported that differential gene expression could be used as a biomarker for high‐grade cervical lesion identification. The aim was to evaluate the gene expression profile of cervical intraepithelial neoplasia (CIN) to identify a gene expression signature of CIN2+ in liquid‐based cytology (LBC) samples. Methods: LBC samples (n = 85) obtained from women who underwent colposcopy were included with benign (n = 13), CIN1 (n = 26), CIN2 (n = 16), and CIN3 (n = 30) diagnoses. After RNA isolation, gene expression profiling was performed using the nCounter PanCancer Pathways, which consists of 730 cancer‐related genes. The genes identified were in silico expression evaluated using the UALCAN database. An accurate prediction model to discriminate CIN2+ from

The actual 5-year survival rates for Gynecological Endometrioid Adenocarcinoma with Squamous Differentiation (GE-ASqD) are rarely reported. The purpose of this study was to evaluate how histological subtypes affected long-term survivors of GE-ASqD (> 5 years). We conducted a retrospective analysis of patients diagnosed GE-ASqD from the Surveillance, Epidemiology, and End Results database (2004–2015). In order to conduct the studies, we employed the chi-square test, univariate cox regression, and multivariate cox proportional hazards model. A total of 1131 patients with GE-ASqD were included in the survival study from 2004 to 2015 after applying the inclusion and exclusion criteria and the sample randomly split into a training set and a test set at a ratio of 7:3. Five machine learning algorithms were trained based on nine clinical variables to predict the 5-year overall survival. The AUC of the training group for the LR, Decision Tree, forest, Gbdt, and gbm algorithms were 0.809, 0.336, 0.841, 0.823, and 0.856 respectively. The AUC of the testing group was 0.779, 0.738, 0.753, 0.767 and 0.734, respectively. The calibration curves confirmed good performance of the five machine learning algorithms. Finally, five algorithms were combined to create a machine learning model that forecasts the 5-year overall survival rate of patients with GE-ASqD. [ABSTRACT FROM AUTHOR]

Background: Endometrial cancer is of increasing concern in several countries, including Brazil, in part because of an ageing population, declines in fertility, and the increasing prevalence of obesity. Although endometrial tumors had lagged behind other cancer types in terms of treatment improvements, molecular characterization of these tumors is paving the way for novel therapies and an expansion of the therapeutic arsenal. We aimed to help medical oncologists who manage patients with recurrent or metastatic endometrial cancer in the Brazilian healthcare setting. Methods: The panel, composed of 20 medical oncologists, convened in November 2021 to address 50 multiple-choice questions on molecular testing and treatment choices. We classified the level of agreement among panelists as (1) consensus (=75% choosing the same answer), (2) majority vote (50% to <75%), or (3) less than majority vote (<50%). Results: Consensus was present for 25 of the 50 questions, whereas majority vote was present for an additional 23 questions. Key recommendations include molecular testing for every patient with recurrent/metastatic endometrial cancer; choice of first-line treatment according to microsatellite instability and HER2, with the addition of programmed death ligand 1 (PD-L1) and hormone receptors (HRs) for second-line therapy; carboplatin and paclitaxel as the preferred option in first-line treatment of HER2-negative disease, with the addition of trastuzumab in HER2-positive disease; pembrolizumab plus lenvatinib as a key option in second line, regardless of HER2, PD-L1 or HRs; and various recommendations regarding treatment choice for patients with distinct comorbidities. Conclusion: Despite the existing gaps in the current literature, the vast majority of issues addressed by the panel provided a level of agreement sufficient to inform clinical practice in Brazil and in other countries with similar healthcare environments. [ABSTRACT FROM AUTHOR]

Objectives: Currently, endometrial adenocarcinoma lacks an effective prognostic indicator. This study was to develop and validate a gene biomarker and a nomogram to predict the survival of endometrial adenocarcinoma, explore potential mechanisms and select sensitive drugs. Methods: 425 endometrial adenocarcinoma cases with RNA sequencing data from TCGA were used to identify the most immune-related module by WGCNA. As an external test set, 103 cases from GSE17025 were used. Immune-related genes were downloaded from Innate DB. The three sets of data were used to identify the prognostic genes. Based on 397 cases with complete clinical data from TCGA, randomly divided into the training set (n = 199) and test set (n = 198), we identified CXCR3 as the prognostic gene biomarker. Age, grade, FIGO stage, and risk were used to develop and validate a predictive nomogram. AUC, C-index, calibration curve and K–M estimate evaluated the model's predictive performance. KEGG enrichment analysis, immune functions, TMB, the effectiveness of immunotherapy, and drug sensitivity between the high-risk and low-risk groups. Results: CXCR3 was identified as a prognostic biomarker. We calculated the risk score and divided the cases into the high-risk and low-risk groups by the median value of the risk score. The OS of the high-risk group was better than the low-risk group. The risk was the prognostic indicator independent of age, grade, and FIGO stage. We constructed the nomogram including age, grade, FIGO stage, and risk to predict the prognosis of endometrial adenocarcinoma. The top five KEGG pathways enriched by the DEGs between the high- and low-risk groups were viral protein interaction with cytokine and cytokine receptors, cytokine-cytokine receptor interaction, chemokine signaling pathway, natural killer cell-mediated cytotoxicity, and cell adhesion molecules. We analyzed the difference in immune cells and found that CD8+ T cells, activated CD4+ T cells, T helper cells, monocytes, and M1 macrophages were infiltrated more in the low-risk group. However, M0 macrophages and activated dendritic cells were more in the high-risk group. The immune function including APC coinhibition, APC costimulation, CCR, checkpoint, cytolytic activity, HLA, inflammation-promoting, MHC-I, parainflammation, T cell coinhibition, T cell costimulation, type I-IFN-response, and type II-IFN-response were better in the low-risk group. TMB and TIDE scores were both better in the low-risk group. By 'the pRRophetic' package, we found 56 sensitive drugs for different risk groups. Conclusion: We identified CXCR3 as the prognostic biomarker. We also developed and validated a predictive nomogram model combining CXCR3, age, histological grade, and FIGO stage for endometrial adenocarcinoma, which could help explore the precise treatment. [ABSTRACT FROM AUTHOR]

We aimed to examine the effect of the squamous differentiation on survival outcomes of women with endometrioid adenocarcinoma. We retrospectively reviewed the patients with endometrioid adenocarcinoma who underwent primary surgical treatment in a tertiary referral hospital. Sixty-nine patients having squamous differentiation constituted the case group. Each woman in the case group was matched with two patients in the control group based on age, disease stage, tumour grade, lymphovascular space invasion, tumour size, myometrial invasion, type of surgery and adjuvant therapy. During the follow-up, the recurrence rates were similar between the case (5/69, 7.2%) and control (10/138, 7.2%) groups (p = 1.0). The 5-year disease-free survival rate was 90.2% for the case group and 88.6% for the control group (p =.51). The 5-year overall survival rate was 94.6% for the case group and 91.8% for the control group (p =.12). Squamous differentiation seems to have no impact on the prognosis of patients with endometrioid adenocarcinoma. What is already known on this subject? A focus of squamous differentiation is recognised in 12.8–25% of women with endometrioid adenocarcinoma. The prognostic value of the squamous differentiation was evaluated in several previous studies. However, it could not be clarified due to the conflicting results of these studies. What do the results of this study add? The probable confounding effects of well-known prognostic factors including age at diagnosis, International Federation of Gynaecology and Obstetrics stage, tumour grade, lymphovascular space invasion, tumour size, myometrial invasion, type of surgery and adjuvant therapy were eliminated with the case-control study design in the current study. Our findings indicate that the presence of squamous differentiation does not have any prognostic effect in endometrioid type endometrial cancer. What are the implications of these findings for clinical practice and/or further research? The molecular prognosticators of endometrial cancer were extensively studied in recent years. It is likely that clinicopathological and molecular prognostic factors will be integrated for predicting prognosis as a part of routine clinical practice soon. In this context, the prognostic value of the squamous differentiation in endometrioid adenocarcinomas may further be clarified by larger and multicentric studies that utilise central pathology review. [ABSTRACT FROM AUTHOR]

Endometrioid endometrial carcinomas (EEC) are common malignant lesions of the female genital tract, with incidence and risk factors that raise issues to improve histopathological prognostic factors. The study included 50 EEC cases, for which the clinicopathological parameters represented by age, risk factors, tumor grade, histological differences, invasion pattern, tumor stage and association of endometrial hyperplasia were analyzed statistically. The results indicated the predominance of EEC in the 7th decade of life, with associated risk factors (78%), more frequently well differentiated (52%), with no other specifications related to differentiation (NOS, 60%), with irregular invasion pattern (66%) in<50% of the myometrial wall (48%). Irregular pattern, microcystic, elongated, and fragmented (MELF) pattern and myoinvasion associated with vascular invasion (MVI) pattern were significantly associated with high grade and advanced stage tumors. With the exception of EEC-NOS and squamous differentiation, all other tumors were associated with low grade (G1). In this study there was a tendency to associate the age group of 60-69 years with the presence of endometrial hyperplasia and with high grade and advanced stage. Apart from the high grade and advanced stage, in the aggressive profile of the EEC can be included as the clinicopathological parameters the 7th decade of life and the irregular, MELF and MVI invasion patterns. [ABSTRACT FROM AUTHOR]

TP53 and ARID1A are frequently mutated across cancer but rarely in the same primary tumor. Endometrial cancer has the highest TP53-ARID1A mutual exclusivity rate. However, the functional relationship between TP53 and ARID1A mutations in the endometrium has not been elucidated. We used genetically engineered mice and in vivo genomic approaches to discern both unique and overlapping roles of TP53 and ARID1A in the endometrium. TP53 loss with oncogenic PIK3CAH1047R in the endometrial epithelium results in features of endometrial hyperplasia, adenocarcinoma, and intraepithelial carcinoma. Mutant endometrial epithelial cells were transcriptome profiled and compared to control cells and ARID1A/PIK3CA mutant endometrium. In the context of either TP53 or ARID1A loss, PIK3CA mutant endometrium exhibited inflammatory pathway activation, but other gene expression programs differed based on TP53 or ARID1A status, such as epithelial-to-mesenchymal transition. Gene expression patterns observed in the genetic mouse models are reflective of human tumors with each respective genetic alteration. Consistent with TP53-ARID1A mutual exclusivity, the p53 pathway is activated following ARID1A loss in the endometrial epithelium, where ARID1A normally directly represses p53 pathway genes in vivo, including the stress-inducible transcription factor, ATF3. However, co-existing TP53-ARID1A mutations led to invasive adenocarcinoma associated with mutant ARID1A-driven ATF3 induction, reduced apoptosis, TP63+ squamous differentiation and invasion. These data suggest TP53 and ARID1A mutations drive shared and distinct tumorigenic programs in the endometrium and promote invasive endometrial cancer when existing simultaneously. Hence, TP53 and ARID1A mutations may co-occur in a subset of aggressive or metastatic endometrial cancers, with ARID1A loss promoting squamous differentiation and the acquisition of invasive properties. Author summary: Endometrial cancer is the most commonly diagnosed gynecologic malignancy in the United States, with annual incidence continuing to rise. Although the majority of endometrial cancer patients have an excellent overall prognosis if the disease is confined to the endometrium, myometrial invasion and metastasis to other sites correlate with poor survival. Here, we used genetically engineered mice, in vivo genomics, and public cancer patient data to understand the relationship between TP53 and ARID1A, two of the most commonly mutated genes in endometrial cancer, in the context of mutant PIK3CA. Mutations in TP53 and ARID1A change different aspects of endometrial cell health but also share some similarities. ARID1A mutations specifically promote cancer cells to invade nearby tissue, a hallmark of metastasis, associated with squamous differentiation. Mice with co-existing TP53 and ARID1A mutations developed more invasive disease. Our studies suggest that co-existing TP53 and ARID1A tumor mutations may promote invasion and metastasis. [ABSTRACT FROM AUTHOR]

Background: Minimally invasive surgery for early cervical cancer is debated. We developed this new vaginal-assisted gasless laparoendoscopic single-site radical hysterectomy for early cervical cancer, and we aimed to evaluate the feasibility and safety of this surgical procedure and observe the early oncologic outcomes. Methods: From January 2019 to August 2020, patients with early cervical cancer who underwent vaginal-assisted gasless laparoendoscopic single-site radical hysterectomy were studied retrospectively. The clinical characteristics, pathologic outcomes, perioperative outcomes, and follow-up details of the patients were recorded. Results: Forty-eight patients underwent vaginal-assisted gasless laparoendoscopic single-site radical hysterectomy were included, 14 (29.2%) with stage IB1, 13 (27.1%) with stage IB2, 7 (14.6%) with stage IB3, 10 (20.8%) with stage IIA1, and 4 (8.3%) stage with IA2. The mean age at diagnosis was 50.4 (range 28–72) years old. The mean operative time was 237.3 min (range 162–393), and the mean estimated blood loss was 246.5 ml (range 80–800). No intraoperative complications occurred, and there were no patients who were readmitted. Histological types were distributed as follows: squamous cell carcinoma 72.9%, adenocarcinoma 10.4%, and adenosquamous cell carcinoma 16.7%. There were 2 patients (4.2%) with positive nodes, 20 patients (41.7%) with positive lymphovascular space invasion, and 2 patients (4.2%) with positive parametria. Twenty-eight patients (58.3%) received adjuvant therapy after the operation. With a mean follow-up of 17.7 months (range 6–26), there were no recurrent cases, and 11 patients (22.9%) suffered lower limb lymphoedema. Conclusions: The vaginal-assisted gasless laparoendoscopic single-site radical hysterectomy might be a feasible technique for early cervical cancer, with promising short-term oncological outcomes and safety. A prospective study with more patients and longer follow-up periods should be performed to further evaluate the safety and oncological outcomes. [ABSTRACT FROM AUTHOR]

Melanoma is the most aggressive skin cancer. Since diagnosis is visual, it is critical to evaluate if students acquire enough knowledge for early detection during medical school. To assess the melanoma knowledge of first-year (freshman) and sixth-year (senior) medical students, in a Brazilian Institution. It was a transversal and quantitative study. A questionnaire with sociodemographic data, knowledge about melanoma, and the habit of skin self-exam was filled out by medical students. A total of 128 first-year and 122 seniors students were included. All the sixth-year students knew melanoma as a skin cancer compared with 46.09% of the first-year students. Melanoma clinical characteristics were known by 30.51% of the freshman and 97.54% of seniors. However, they did not know the most usual site of melanoma occurrence (79.66% of first-year students and 24.59% of senior). About the skin self-exam, only 50% of first-year students and 53.28% of senior had the habit of doing it sometimes. Medical school was effective in providing knowledge about melanoma and its features. However, this was not reflected in an increase in the number of students that did the skin self-exam, which indicates the need for new approaches in teaching. [ABSTRACT FROM AUTHOR]

Background: Lung cancer patients undergoing palliative chemotherapy exhibit many symptoms related to the disease, such as adverse events and infectious complications during treatment, which impacts directly their health-related quality of life (HRQOL). Nutritional status is a relevant aspect among advanced cancer patients under palliative care and food supplementation has the potential to reduce treatment-related adverse effects and improve the nutritional status. The product named AferBio® is a fermented supplement that has been described as able to provide some benefits, including the capacity to potentiate the effects of anticancer drugs, by promoting the reduction of side effects and ultimately improving HRQOL.Methods/design: A Phase II double-blind placebo-controlled randomized clinical trial to assess the use of food supplementation with AferBio® in Stage IIIB or IV non-small cell lung cancer (NSCLC) patients beginning a second-line palliative mono-chemotherapy. The primary goal is to compare HRQOL scores between the arms of the study over time. The ten first patients included in the present study will undergo an AferBio®toxicity-testing (non-randomized phase). If no significant toxicity is found, the study will move on to the randomized phase. All patients will be randomized in blocks at a 1:1 ratio using the online tool REDCap. ECOG-PS (0-1 versus 2) criteria will be used for stratification. All patients included in the trial will be evaluated at baseline and at each chemotherapy cycle. Each evaluation will include the following: HRQOL (EORTC QLQ-C30, LC13 and IQualiV-Lung), ECOG-PS, anthropometric measurements, clinical and laboratory toxicity assessment and response evaluation.Discussion: During palliative systemic therapy in advanced cancer patients, one of the main goals is the improvement and maintenance of HRQOL, which can be negatively affected by cancer symptoms, cancer- or treatment-related psychosocial difficulties, and chemotherapy toxicity. Thus, much research has been dedicated to the development of new and more effective and/or less toxic cancer therapies. The present study is justified by the testing of a novel food supplement that may reduce some toxicities, thus, having a potential positive impact on the HRQOL of lung cancer patients. The product in question (AferBio®) is already available for sale in Brazil, but has not yet been fully tested in cancer patients.Trial Registration: This Trial was registered on March 19, 2018 with ClinicalTrials.gov , NCT03469063. Protocol version: 2.0 from March 26, 2018. Trial status: Patient enrollment in the study began in April, 2018. [ABSTRACT FROM AUTHOR]

Aim: The literature lacks direct evidence comparing the different regimens evaluated in the second-line treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).Methods: We conducted a network meta-analysis (NMA) of the randomized controlled Phase III trials reporting on the second-line drug treatment options in R/M SCCHN.Results: The eligible trials included 11 regimens among which six targeted therapies, two immune checkpoint inhibitors and three chemotherapy regimens. Only nivolumab has shown statistically significant superiority over methotrexate in terms of overall survival (HR: 0.64; 95% CI: 0.43-0.96) and objective response rate (OR: 2.51; 95% CI: 1.07-5.86).Conclusion: Based on the efficacy and safety outcomes of this network meta-analysis, nivolumab seems the most favorable regimen inthe management of R/M SCCHN. [ABSTRACT FROM AUTHOR]

Background and Objectives: We aimed to explore the capacity of the combined ratio of biomarkers to predict the recurrence of Stage I-III endometrial cancer (EC)., Methods: A total of 473 patients were enrolled after screening. The cut-off value of the ratio was calculated by the receiver operating characteristic curve (ROC). The univariate and multivariate Cox regression analysis was used to assess the correlation between the combined ratio and the recurrence of EC. The differences of clinicopathological parameters between the two groups divided based on the threshold were compared., Result: The ROC curve showed that 0.92 was the optimal cut-off value of the ratio ([ER + PR]/[P53 + Ki67]). The multivariate analysis demonstrated that only International Federation of Gynecology and Obstetrics stage (p = .031) and the combined ratio (p = .004) were independent risk factors of recurrence. The 3-year recurrence-free survival (RFS) and overall survival of patients in the low-ratio group were 54.1% and 66.8%, respectively; while in the high-ratio group were 94.9% and 97.9%, respectively (p < .001). The 3-year RFS of 194 patients, who did not receive the adjuvant therapy, was 54.7% and 97.2% between two groups (p < .001)., Conclusions: The optimal cut-off value (0.92) of the combined ratio was demonstrated to be better to predict the recurrence of EC than a single immunohistochemical marker., (© 2020 Wiley Periodicals LLC.)

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cause of cancer death worldwide. Its treatment is complex and evolving. In general, early-stage disease may be managed with single-modality treatment while an advanced stage (about 60% of clinical presentation) needs a multidisciplinary approach. In this setting concurrent chemoradiation has been associated with improvement in locoregional control and organ preservation, but at the cost of significant acute and chronic toxicity. Molecular target therapies specially directed to epidermal growth factor receptor (EGFR) might improve the outcomes and reduce toxicities. In recurrent-metastatic (R/M) HNSCC, cetuximab, a monoclonal antibody against EGFR, plus platinum-based chemotherapy (CT) allow an overall survival (OS) of about 10 months. However, the prognosis for R/M-HNSCC remains dismal and additional efforts are needed. At the 2013 American Society of Clinical Oncology (ASCO) Meeting, data on induction CT, anti-EGFR inhibitors, innovative molecular targets and predictor factors were reported. Further results on target therapies were presented at the European Cancer Congress (ECC) 2013, where a large study also showed that hyperfractionated radiotherapy (RT) improve OS rates compared with standard RT. The aim of this review is to discuss current standards and emerging therapies by considering recent new updates. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: Paired box protein-8 (PAX-8) immunohistochemical expression can be used as a diagnostic marker for epithelial cells tumors. This study aimed at investigating the immunohistochemical expression of PAX-8 among Sudanese females diagnosed with cervical, endometrial, and ovarian cancers between December 2017 and May 2019 by studying their Formalin-fixed paraffin embedded blocks. Results: Sixty patients diagnosed with female reproductive tract cancers were included who aged 58.7 ± 6.9 years (range, 43—71). Cervix was the most common cancer site in 51/60 (85%) patients. Regarding cancer stage, there was 17 (28%) and 14 (23%) of the study population had stage 3B and 2B, respectively. The histopathological diagnosis included 20 (44%), 13 (29%), and 12 (27%) poorly, moderately, and well differentiated cervical squamous cell carcinoma (SCC) as well as 11 (73%), 2 (13%), 1 (7%), and 1 (7%) endometrial adenocarcinoma, metastatic adenocarcinoma, endocervical adenocarcinoma, and ovarian mucinous cyst adenocarcinoma, respectively. PAX-8 was positively expressed in 9 endometrial adenocarcinoma, 1 endocervical adenocarcinoma and 1 ovarian mucinous cyst adenocarcinoma, 2 poorly, and 1 moderately differentiated SCC. All patients diagnosed with well differentiated SCC and metastatic adenocarcinoma showed no expression of PAX-8. A statistically significant was seen for PAX-8 expression and the different histopathological diagnosis, P value < 0.001. [ABSTRACT FROM AUTHOR]