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Breast conserving treatment typically involves surgical excision of tumor and adjuvant radiotherapy targeting the breast area or tumor bed. Accurately defining the tumor bed is challenging and lead to irradiation of greater volume of healthy tissues. Preoperative stereotactic body radiotherapy (SBRT) which target tumor may solves that issues. We conducted a systematic literature review to evaluates the early toxicity and cosmetic outcomes of this promising treatment approach. Secondary we reviewed pathological complete response (pCR) rates, late toxicity, patient selection criteria and radiotherapy protocols. We retrieved literature from PubMed, Scopus, Web of Science, Cochrane, ScienceDirect, and ClinicalTrials.gov. The study adhered to the PRISMA 2020 guidelines. Ten prospective clinical trials (7 phase II, 3 phase I), encompassing 188 patients (aged 18-75 years, cT1-T3 cN0-N3 cM0, primarily with ER/PgR-positive, HER2-negative status,), were analyzed. Median follow-up was 15 months (range 3-30). Treatment involved single-fraction SBRT (15-21Gy) in five studies and fractionated (19.5-31.5Gy in 3 fractions) in the rest. Time interval from SBRT to surgery was 9.5 weeks (range 1-28). Acute and late G2 toxicity occurred in 0-17% and 0-19% of patients, respectively, G3 toxicity was rarely observed. The cosmetic outcome was excellent in 85-100%, fair in 0-10% and poor in only 1 patient. pCR varied, showing higher rates (up to 42%) with longer intervals between SBRT and surgery and when combined with neoadjuvant systemic therapy (up to 90%). Preoperative SBRT significantly reduce overall treatment time, enabling to minimalize volumes. Early results indicate excellent cosmetic effects and low toxicity.
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Neoplasias de la Mama , Radiocirugia , Humanos , Radiocirugia/métodos , Radiocirugia/efectos adversos , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/patología , Femenino , Cuidados PreoperatoriosRESUMEN
Purpose or Objective-The aim of the study is to evaluate the efficacy and safety of SBRT on detectable prostate bed recurrence in RT-naïve prostate cancer patients. MATERIALS AND METHODS: Eighty-six patients who underwent SBRT for macroscopic bed recurrence after prostatectomy were retrospectively included. Patients were treated based on mpMRI or choline/PSMA PET. RESULTS: The median time to biochemical relapse (BCR) after RP was 46 months, with a median PSA at restaging of 1.04 ng/mL. Forty-six patients were staged with mpMRI and choline/PSMA PET, while ten and thirty were treated based on PET and MRI only, respectively. Only one late G ≥ 2 GI toxicity was observed. With a median BCR follow-up of 14 months, twenty-nine patients experienced a BCR with a median PSA at recurrence of 1.66 ng/mL and a median survival free from the event of 40.1 months. The median time to BCR was 17.9 months. Twenty-seven patients had clinical relapse (CR), with a median CR follow-up of 16.27 months and a median time to CR of 23.0 months. Biochemical recurrence-free survival at one and two years was 88% and 66%, respectively, while clinical recurrence-free survival at one and two years was 92% and 82%, respectively. Regarding local relapses, seven were in the field of treatment, while eight of them were outside the field of treatment. CONCLUSIONS: Data showed that SBRT targeting only the macroscopic bed recurrence instead of the whole prostate bed is safe and effective. Additional data and longer follow-ups will provide a clearer indication of the appropriate treatment and staging methodology for these patients.
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AIM: The study aims to report the feasibility and safety of palliative hypofractionated radiotherapy targeting macroscopic bladder tumors in a monocentric cohort of frail and elderly bladder cancer patients not eligible for curative treatments. METHODS: Patients who underwent hypofractionated radiotherapy to the gross disease or to the tumor bed after transurethral resection of bladder tumor from 2017 to 2021 at the European Institute of Oncology IRCCS, were retrospectively considered. Schedules of treatment were 30 and 25 Gy in 5 fractions (both every other day, and consecutive days). Treatment response was evaluated with radiological investigation and/or cystoscopy. Toxicity assessment was carried out according to RTOG/EORTC v2.0 criteria. RESULTS: A total of 16 patients were included in the study, of these 11 received hypofractionated radiotherapy on the macroscopic target volume and five on the tumor bed after transurethral resection of bladder tumor. No grade (G) >2 acute toxicities were described after treatment for both groups. Only one patient in the group receiving radiotherapy on the macroscopic disease reported G4 GU late toxicity. Ten patients had available follow-up status (median FU time 18 months), of them six had complete response, one had stable disease, and three had progression of disease. The overall response rate and disease control rate were 60% and 70%, respectively. CONCLUSION: Our preliminary data demonstrate that palliative hypofractionated radiotherapy for bladder cancer in a frail and elderly population is technically feasible, with an acceptable toxicity profile. These outcomes emphasize the potential of this approach in a non-radical setting and could help to provide more solid indications in this underrepresented setting of patients.
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Anciano Frágil , Hipofraccionamiento de la Dosis de Radiación , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/radioterapia , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/cirugía , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Estudios Retrospectivos , Resultado del Tratamiento , Estudios de Factibilidad , Invasividad NeoplásicaRESUMEN
Most of the currently used cancer immunotherapies inhibit the programmed cell death protein 1 (PD1)-programmed cell death 1 ligand 1 (PDL1) axis of T-cells. However, dendritic cells (DCs) controlled by natural killer (NK) cells via the FMS-related tyrosine kinase 3 (FLT3) axis are necessary for activation of T-cells. The aim of the study was to evaluate FLT3 as a prognostic factor and determine its role in immune infiltration (with emphasis on NK cells and DCs). Using The Cancer Genome Atlas (TCGA) database, we performed bioinformatic analysis of the gene expression datasets of 501 lung squamous cell carcinoma (LUSC) and 515 lung adenocarcinoma (LUAD) patient who had corresponding clinical data [analysis was performed in R (version 4.2.0)]. Disease-free survival (DFS) differed between the FLT3-low and FLT3-high expression groups, respectively, in LUSC (61.0 vs 71.3 months P = 0.075) and LUAD (32.7 vs 47.5 months P = 0.045). A tumor microenvironment (TME) with high immune infiltration and rich in T-cell exhaustion markers was observed in the FLT3-high group. We showed overexpression of NK cell and DC gene signatures in the FLT3-high expression group as well as overexpression of key effector genes of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes protein (STING) pathway, which is crucial in response to radiotherapy. High expression of FLT3 in the TME was associated with immune cell infiltration (especially of NK cells and DCs), increased expression of T-cell exhaustion markers and expression of effector genes of the cGAS-STING pathway, which may consequently increase susceptibility to immunotherapy and radiotherapy. High FLT3 expression correlated with prolonged DFS in the LUSC and LUAD cohorts.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Microambiente Tumoral , Tirosina Quinasa 3 Similar a fms , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Supervivencia sin Enfermedad , Tirosina Quinasa 3 Similar a fms/genética , Tirosina Quinasa 3 Similar a fms/metabolismo , Regulación Neoplásica de la Expresión Génica , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/mortalidad , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Pronóstico , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Adulto , Anciano de 80 o más AñosRESUMEN
OBJECTIVES: To assess the role of the positron emission tomography with fluorine-18-deoxyglucose (PET/CT) in the detection of recurrent serous ovarian cancer in patients with normal serum CA125 level. MATERIAL AND METHODS: Thirty-one patients with suspected recurrent serous ovarian cancer with normal (< 35 IU/mL) serum CA125 level and no prior recurrence underwent PET/CT imaging. The results of the PET/CT were analyzed considering clinical data of the patients, histological diagnosis and 6 months follow-up. RESULTS: The patients were referred to the PET/CT due to suspected relapse in imaging tests (CT - 11 cases, US - 3 cases, MRI - 2 cases; n = 16; 51.6%), clinical examination (n = 4; 12.9%) and clinical symptoms (n = 11; 35.5%). The recurrent serous ovarian cancer was present in 16 patients (51.6%). In 9 these cases (56.3%) the recurrences were diagnosed in patients aged 51-70 years. In 15 cases (93.8%) the recurrences were diagnosed within 24 months after treatment. There were 15 true positive (48.4%), 12 true negative (38.7%), 3 false positive (9.7%) and 1 false negative (3.2%) PET/CT results. Sensitivity, specificity, positive and negative predictive value of the PET/CT were calculated as 93.8% (95% CI, 86.1-97.4%), 80.0% (95% CI, 69.7-88.9%), 83.3% (95% CI, 74.3-90.4%) and 92.3% (95% CI, 84.2-98.3%), respectively. CONCLUSIONS: In patients with a diagnosis of complete remission after treatment for serous ovarian cancer, even a multifocal recurrence may occur during follow up despite normal serum CA125 levels. Our results showed a usefulness of the PET/CT in detecting and differentiating malignant from benign lesions in patients with normal serum CA125 levels but inconclusive results in other imaging tests. We observed false results of the PET/CT for lesions in parotid gland, mesorectal adipose tissue and mediastinal lymph nodes.
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Combining systematic biopsy (SB) with targeted biopsy (TB) in the case of a positive result from multiparametric magnetic resonance imaging (mpMRI) is a matter of debate. The Prostate Imaging Reporting and Data System (PIRADS) score of 5 indicates the highest probability of clinically significant prostate cancer (csPC) detection in TB. Potentially, omitting SB in the case of PIRADS 5 may have a marginal impact on the csPC detection rate. The aim of this study was to determine whether SB can be avoided in the case of PIRADS 5 and to identify potential factors allowing for performing TB only. This cohort study involved n = 225 patients with PIRADS 5 on mpMRI (PIRADS 2.0/2.1) who underwent transperineal or transrectal combined biopsy (CB). CsPC was diagnosed in 51.6% (n = 116/225) of cases. TB and SB resulted in the detection of csPC in 48% (n = 108/225) and 20.4% (n = 46/225) of cases, respectively (TB vs. SB, p < 0.001). When the TB was positive, SB detected csPC in n = 38 of the cases (38/108 = 35%). SB added to TB significantly improved csPC detection in 6.9% of cases in absolute terms (n = 8/116) (TB vs. CB, p = 0.008). The multivariate regression model proved that the significant predictors of csPC detection via SB were the densities of the prostate-specific antigen-PSAD > 0.17 ng/mL2 (OR = 4.038, 95%CI: 1.568-10.398); primary biopsy setting (OR = 2.818, 95%CI: 1.334-5.952); and abnormal digital rectal examination (DRE) (OR = 2.746, 95%CI: 1.328-5.678). In a primary biopsy setting (n = 103), SB detected 10% (n = 6/60) of the additional cases of csPC (p = 0.031), while in a repeat biopsy setting (n = 122), SB detected 3.5% (n = 2/56) of the additional cases of csPC (p = 0.5). In the case of PSAD > 0.17 ng/mL2 (n = 151), SB detected 7.4% (n = 7/95) of additional cases of csPC (p = 0.016), while in the case of PSAD < 0.17 ng/mL2 (n = 74), SB detected 4.8% (n = 1/21) of the additional cases of csPC (p = 1.0). The omission of SB had an impact on the csPC diagnosis rate in patients with PIRADS 5 score lesions. Patients who have already undergone prostate biopsy and those with low PSAD are at a lower risk of missing csPC when SB is avoided. However, performing TB only may result in missing other csPC foci located outside the index lesion, which can alter treatment decisions.
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BACKGROUND: The exact role of positron emission tomography with fluorine-18-deoxyglucose ([18F]FDG PET/CT) in an early diagnosis of relapsed ovarian cancer is not clearly defined. The aim of the study was to assess the value of [18F]FDG PET/CT in the detection and differentiation of recurrent ovarian cancer. MATERIAL AND METHODS: Eighty-four patients with suspected recurrent ovarian cancer underwent [18F]FDG PET/CT examination. Results of PET/CT were analyzed taking into account clinical data of the patients, histological diagnosis, and 6-month follow-up. RESULTS: The [18F]FDG PET/CT examinations showed abnormal findings in 67 patients (79.76%). There were 63 true positive results (75.00%), 14 true negative (16.67%), 4 false positive (4.76%), and 3 false negative (3.57%) results. Sensitivity, specificity, positive and negative predictive values of [18F]FDG PET/CT were 95%, 78%, 94%, and 82%, respectively. In patients with elevated serum Ca 125 concentration (n = 43), sensitivity and specificity of [18F]FDG PET/CT was 95.00% and 66.67%, respectively. Recurrence was confirmed in 22 (88.00%) of 25 patients referred for [18F]FDG PET/CT due to suspected relapse in imaging tests. CONCLUSIONS: A high frequency of recurrent ovarian cancer detected in the [18F]FDG PET/CT examinations due to increased Ca 125 concentration in patients without clinical symptoms and without changes in other imaging tests confirmed the usefulness of [18F]FDG PET/CT in such cases. In patients with suspected recurrent ovarian cancer implied in radiological findings, [18F]FDG PET/CT results in most cases differed from the original results of imaging examination. Our results showed high accuracy of [18F]FDG PET/CT in the evaluation of recurrent ovarian cancer and presented this diagnostic method as a useful tool in detecting and differentiating suspected lesions in this group of patients.
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Neoplasias Ováricas , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Femenino , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Fluorodesoxiglucosa F18 , Recurrencia Local de Neoplasia/diagnóstico por imagen , Tomografía de Emisión de Positrones , Sensibilidad y Especificidad , Neoplasias Ováricas/diagnóstico por imagen , RadiofármacosRESUMEN
Introduction: Cabozantinib is an oral inhibitor of MET, AXL, and vascular endothelial growth factor receptors. It has an immunomodulatory effect and may influence the tumor's microenvironment and make mutated cells more sensitive to immune-mediated killing. These properties have made cabozantinib an effective drug for first-line or subsequent-line treatment after progression of metastatic renal cell carcinoma (mRCC), even after immunotherapy. Material and methods: Seventy-one patients with mRCC were treated with second or further lines of cabozantinib at the Department of Genitourinary Oncology, Maria Sklodowska-Curie National Research Institute of Oncology. This study retrospectively evaluated the effectiveness of cabozantinib in subsequent lines of treatment. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints. The best overall response (BOR) to cabozantinib was the secondary endpoint. For this purpose, Cox's proportional hazard model was used. Results: The median PFS was 11 months (5; 23) and the median OS was 16 months (10; 42) and differed significantly in the second and further lines of treatment. Progression in the second and further lines was observed in 28 (93%) and 27 (66%) patients, respectively (p = 0.006). Partial response as the BOR was observed in one patient (3%) in the second line and 13 patients (32%) in the further lines (p = 0.012). Conclusions: Cabozantinib has antitumor effects in the second and further lines of treatment. In this study we observed high efficiency of cabozantinib in further lines of treatment.
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Introduction: Geriatric patients with metastatic renal cell carcinoma (mRCC) are underrepresented in clinical trials. Evaluation of the efficacy of the treatment and assignation of individuals to proper prognostic groups is an absolute necessity to guarantee them the best possible care. Material and methods: A total of 138 geriatric patients with mRCC treated with first-line tyrosine kinase inhibitors (TKIs) at the Maria Sklodowska-Curie National Research Institute of Oncology were retrospectively analyzed to determine whether the body mass index (BMI) and pan-immune-inflammation value (PIV) are prognostic values for overall survival (OS) and progression-free survival (PFS) in this type of cancer. For this purpose, Cox's proportional hazard model was used. Results: The median duration of follow-up for surviving patients was 46.6 (95% CI: 17.4-75.8) months. The median OS and PFS were respectively 33.8 months (95% CI: 23.8-47.8) and 19.1 months (95% CI: 15.0-23.3). BMI (p = 0.034) and PIV (p < 0.001) were statistically significantly associated with OS, and PIV (p = 0.001) was statistically significantly associated with PFS. The risk of death for patients from the high-PIV group (cut-off point: 548) was 3.4 times higher than for those with lower PIV values. The corresponding risk of progression for patients from the high-PIV group was 2.2 times higher. The G8 geriatric screening tool was not identified as a prognostic factor. Conclusions: Lower PIV and obesity are associated with longer OS in geriatric mRCC patients treated with TKIs in the first line. These factors may be considered while making treatment decisions if further studies show the same results.
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Introduction: Assessment of renal tumour masses is based on conventional imaging studies (computer tomography or magnetic resonance), which does not allow characterisation of the histopathological type. Moreover, the prediction of prognosis in localised and metastatic renal cell carcinoma requires improvement as well. Analysis of circulating free DNA (cfDNA) in blood is one of the variants of liquid biopsy that may improve diagnostics and prognosis issues of patients with renal tumour masses suspected to be renal cell carcinoma. The aim of the study was to assess the diagnostic and prognostic role of preoperative cfDNA concentration in the plasma samples of clear cell renal cell carcinoma (ccRCC) patients. Material and methods: The preoperative plasma cfDNA concentration was assessed in ccRCC patients (n = 46) and healthy individuals (control group) (n = 17). The circulating free DNA concentration was reflected by the 90 bp DNA fragments determined by real-time polymerase chain reaction. Results: The median cfDNA concentration was significantly higher in ccRCC patients (n = 46) compared to the control g roup (n = 17) (2588 ±2554 copies/ml vs. 960 ±490 copies/ml, p < 0.01). In multivariate analysis, the preoperative plasma cfDNA concentration was the significant factor increasing the probability of ccRCC detection (OR: 1.003; 95% CI: 1.001-1.005). The median cfDNA concentration depended on the stage of ccRCC; it was higher in metastatic ccRCC patients (n = 11) compared to non-metastatic ccRCC patients (n = 35) (3619 ±4059 copies/ml vs. 2473 ±1378 copies/ml, p < 0.03). Kaplan-Meier survival analysis demon-strated that patients with high cfDNA values (above 2913 copies/ml) had significantly worse cancer-specific survival (HR: 4.5; 95% CI: 1.3-16.9, log-rank Mantel-Cox test p = 0.015). Conclusions: Preoperative plasma cfDNA concentration has diagnostic and prognostic potential in ccRCC pa-tients.
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Cutaneous squamous cell carcinoma (cSCC) is the second most frequent non-melanoma skin cancer. The standard curative treatment is surgical resection, but the treatment of locally advanced and metastatic disease apart from radiotherapy is currently based on cemiplimab. Cemiplimab has demonstrated efficacy in the treatment of advanced and metastatic cSCC in clinical trials, although real-world data are still limited. We present four cases of cSCC, which showed a tremendous response to cemiplimab-one patient achieved complete response and three of them achieved partial response. Immunotherapy with cemiplimab, a recently approved PD1 inhibitor, is an important addition to the cutaneous oncology therapeutic options that may be considered in patients with advanced disease not amenable to surgery or radiotherapy. In all four cases, the patients postponed visits to the doctor because of the fear of SARS-CoV-2 infection or for administrative and organizational reasons declared difficult access to doctors caused by the pandemic.
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Antineoplásicos Inmunológicos , COVID-19 , Carcinoma de Células Escamosas , Neoplasias Cutáneas , Humanos , Carcinoma de Células Escamosas/patología , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , SARS-CoV-2 , Antineoplásicos Inmunológicos/efectos adversos , PandemiasRESUMEN
The optimal sequence of chemoradiotherapy with immunotherapy is still not established. The patient's immune status may play a role in determining this order. We aim to determine the kinetics of a multi-potential haemopoietic factor FMS-related tyrosine kinase 3 ligand (Flt-3L) during chemoradiotherapy. Our pilot, a single arm prospective study, enrolled patients with rectal cancer who qualified for neoadjuvant chemoradiotherapy. Blood samples for Flt-3L were collected before and every second week of chemoradiotherapy for a complete blood count every week. The kinetics of Flt-3L were assessed using Friedman's ANOVA. A multiple factor analysis (MFA) was performed to find relevant factors affecting levels of serum Flt-3L during chemoradiotherapy. FactoMineR and factoextra R packages were used for analysis. In the 33 patients enrolled, the level of Flt-3L increased from the second week and remained elevated until the end of treatment (p < 0.01). All patients experienced Grade ≥2 lymphopenia with a nadir detected mostly in the 5/6th week. MFA revealed the spatial partitioning of patients among the first and second dimensions (explained by 38.49% and 23.14% variance). The distribution along these dimensions represents the magnitude of early changes of Flt-3L. Patients with the lowest values of Flt-3L change showed the highest lymphocyte nadirs and lowest dose/volume parameters of active bone marrow. Our hypothesis-generating study supports the concept of early initiation of immuno-therapy when the concentration of Flt-3L is high and no lymphopenia has yet occurred.
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BACKGROUND: Patients with diagnosed keratinocyte carcinomas (KCs) have an increased risk of subsequent skin cancers development. Current studies indicate that patients with subsequent tumors should be followed up regularly. However, none of the studies indicate the connection between the specific subtypes and an increased risk for further KCs development. The study assesses the differences in the risk of developing a subsequent skin cancer after a previous diagnosis of KC, especially considering individual types of skin malignances, and identifies potential factors associated with an increased risk of new cutaneous tumor describing non-invasive diagnosis and monitoring. METHODS: Pathology and medical records were examined to identify the characteristics of patients with multiple KCs diagnosed between 1999 and 2019. RESULTS: The study group comprised 13,913 KCs occurring in 10,083 patients. Multiple KCs were observed in 2300 patients (22.8%). The analysis showed aggressive subtypes, multiple tumors, and male sex as significant prognostic factors. CONCLUSIONS: The most crucial risk factors for developing subsequent KC are being of a male gender, an aggressive tumor subtype, and previous history of multiple skin cancers. Basal cell carcinoma subtypes, such as infiltrative basosquamous, with aggressive growth patterns predispose not only to increased risk for the recurrence but are also expected to be at higher risk of subsequent KCs.
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The aim of the study was to assess immunohistochemical CD34, podoplanin and Ki-67 expression in cervical tumour of patients with cervical squamous cell carcinoma (SCC) staged IIB and IIIB, a relationship with selected clinical and histological parameters and its prognostic significance. This prospective study included 52 patients. Microvessel density (MVD) by CD34, lymphatic vessel density (LVD) by podoplanin and the Ki-67 index in specimens from paraffin blocks with cervical SCC tissues were examined. The relationship between these data and selected clinical and histological parameters was analysed. Positive correlation of MVD and the Ki-67 index was observed. No correlation was observed for MVD, LVD and the Ki-67 index in the tumour with staging, grading, length of treatment and squamous cell carcinoma antigen (SCC-Ag) concentration before and after treatment. The expression of MVD, LVD and the Ki-67 index in cervical SCC did not contribute to the risk of relapse and cancer-related death. No relationship was found for MVD, LVD and the Ki-67 index in cervical tumour of patients with locally advanced cervical SCC with staging, grading and serum SCC-Ag level. MVD, LVD and the Ki-67 index in the tumour did not contribute to the risk of relapse or cervical SCC-related death.Impact StatementWhat is already known on this subject? In many patients, invasive cervical squamous cell carcinoma (SCC) is diagnosed in a locally advanced stage, when the prognosis depends on many well-known factors connected with tumour biology, staging and general condition of the patient. Despite numerous studies, the value of immunohistochemical CD34, podoplanin and Ki-67 expression in cervical tumour of these patients is still not well defined.What do the results of this study add? In our prospective study, no relationship for microvessel density (MVD), lymphatic vessel density (LVD) and the Ki-67 index in cervical tumour of patients with locally advanced cervical SCC with staging, grading and serum squamous cell carcinoma antigen (SCC-Ag) level was found. Additionally, MVD, LVD and the Ki-67 index in the tumour did not contribute to the risk of relapse or cervical SCC-related death.What are the implications of these findings for clinical practice and/or further research? Our study underlines the limited value of immunohistochemical CD34, podoplanin and Ki-67 expression in cervical tumour of patients with locally advanced cervical SCC. Further research should be focussed on identifying and validating novel prognostic and predictive factors.
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Carcinoma de Células Escamosas , Vasos Linfáticos , Neoplasias del Cuello Uterino , Femenino , Humanos , Antígenos CD34 , Carcinoma de Células Escamosas/patología , Células Epiteliales , Antígeno Ki-67 , Vasos Linfáticos/patología , Glicoproteínas de Membrana , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Neoplasias del Cuello Uterino/patologíaRESUMEN
Breast cancer (BC) remains a significant healthcare challenge. Routinely, the treatment strategy is determined by immunohistochemistry (IHC)-based assessment of the key proteins such as estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and Ki-67. However, it is estimated that over 75% of deaths result from metastatic tumors, indicating a need to develop more accurate protocols for intertumoral heterogeneity assessment and their consequences on prognosis. Therefore, the aim of this preliminary study was the identification of the expression profiles of routinely used biomarkers (ER, PR, HER2, Ki-67) and additional relevant proteins [Bcl-2, cyclin D1, E-cadherin, Snail+Slug, gross cystic disease fluid protein 15 (GCDFP-15), programmed death receptor 1 (PD-L1), and phosphatase of regenerating liver 3 (PRL-3)] in breast primary tumors (PTs) and paired synchronous axillary lymph node (ALN) metastases. A total of 67 tissue samples met the inclusion criteria for the study. The expression status of biomarkers was assessed in PTs and ALN metastases using tissue microarrays followed by IHC. In 11 cases, the shift of intrinsic molecular BC subtype was noticed between PTs and paired ALN metastases. Moreover, a significant disproportion in E-cadherin presence (p = 0.0002) was noted in both foci, and the expression status of all proteins except for HER2 demonstrated considerable variance (k = 1, p < 0.0001). Importantly, in around 30% of cases, the ALN metastases demonstrated discordance, i.e., loss/gain of expression, compared to the PTs. Intertumoral synchronous heterogeneity in both foci (primary tumor and node metastasis) is an essential phenomenon affecting the clinical subtype and characteristics of BC. Furthermore, a greater understanding of this event could potentially improve therapeutic efficacy.
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OBJECTIVES: In our previous prospective trial on accelerated hypofractionated concomitant radiochemotherapy (AHRT-CHT) for non-small-cell lung cancer (NSCLC), the incidence of grade ≥3 acute esophageal toxicity (AET) was similar to that reported for conventionally fractionated concomitant radiochemotherapy (CFRT-CHT), but its duration was prolonged. Thus, we aimed to compare the duration of grade ≥3 AET between AHRT-CHT and CFRT-CHT. METHODS: Clinical data of 76 NSCLC patients treated with CFRT-CHT (60-66 Gy/2 Gy) during 2015-2020 were retrospectively compared with the data of 92 patients treated with AHRT-CHT (58.8 Gy/2.8 Gy) in the prospective trial. The maximum grade of AET, incidence, and duration of grade ≥3 AET were the end points. Univariate and multivariate analyses were applied to correlate clinical and treatment variables with these end points. RESULTS: Neither the maximum grade of AET (p = 0.71), nor the incidence of grade ≥3 AET (p = 0.87) differed between the two groups. The number of CHT cycles delivered (2 vs 1, p = 0.005) and higher esophagus mean BED (p = 0.009) were significant predictors for a higher maximum grade of AET; older age was a significant predictor for higher incidence of grade ≥3 AET (p = 0.03). The median duration of grade ≥3 AET in AHRT-CHT and CFRT-CHT group was 30 days (range 5-150) vs 7 days (range 3-20), respectively, p = 0.0005. In multivariate analysis, only the AHRT-CHT schedule (p=0.003) was a significant predictor for a longer duration of grade ≥3 AET. CONCLUSION: Despite similar incidence of grade ≥3 AET, its duration is significantly prolonged in NSCLC patients treated with AHRT-CHT compared to CFRT-CHT. ADVANCES IN KNOWLEDGE: Reporting only the rate of grade ≥3 AET in clinical trials may underestimate the real extent of the esophageal toxicity; its duration should also be routinely reported.
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Carcinoma de Pulmón de Células no Pequeñas/terapia , Quimioradioterapia/efectos adversos , Fraccionamiento de la Dosis de Radiación , Esófago/efectos de la radiación , Neoplasias Pulmonares/terapia , Traumatismos por Radiación/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Gravedad del Paciente , Estudios Retrospectivos , TiempoRESUMEN
INTRODUCTION: Human papillomavirus (HPV) is associated with six types of cancer in men and women. A vaccine against HPV, preferably administered before initial sexual intercourse, has been proven to be highly effective in preventing these cancers. An effective healthcare provider recommendation has significant influence on HPV vaccine uptake; therefore, it is critical that medical students receive comprehensive training in this area. AIM: The aim of the study was to assess the knowledge of medical students regarding Human Papillomavirus's (HPV) ways of transmission, risk of cancer development, and vaccination against HPV. This study also investigated factors among medical students that would affect their intention to recommend HPV vaccination to others. MATERIALS AND METHODS: The study was conducted among 1061 (678 women and 383 men) medical students who filled in our questionnaire. The medical students were divided into two subgroups: (1) pre-clinical medical students (MS pre-clinical; first-to third-year students; n = 683) and (2) clinical medical students (MS clinical; fourth-to six-year students; n = 378). RESULTS: A total259 (24.41%) of the 1061 medical students were vaccinated against HPV. We found a significant improvement in the general level of knowledge in the later years of education (4-6) compared to the early years of education (1-3). However, it was demonstrated that, despite medical education advancements, there are still significant gaps of knowledge about the relationship between HPV infection and cancers other than cervical cancer, as well as in relation to the routes by which HPV is transmitted. Medical students' intentions to recommend HPV vaccine to others were related to their own HPV-related knowledge and their own vaccination status. CONCLUSION: Medical students have gaps of knowledge regarding particular issues and aspects of HPV. It is necessary to further educate medical students in the field of prevention and in the treatment of lesions caused by HPV infection. Medical students' intention to recommend the HPV vaccine can be improved by including them and members of their families in the HPV vaccination program.
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PURPOSE: Magnetic resonance imaging (MRI) is routinely used for locoregional staging of rectal cancer and offers promise for the prediction of hematologic toxicity. The present study compares the clinical utility of MRI-based active bone marrow (BMact) delineation with that of CT-based bone marrow total (BMtot) delineation for predicting hematologic toxicity. METHODS: A prospective cohort study was performed. Eligible patients had stage II/III rectal cancer and qualified for preoperative chemoradiotherapy. The BMact areas on T1-weighted MRI were contoured. The impact of the dose-volume parameters of BMact/BMtot and clinical data on hematologic toxicity were assessed. Basic endpoints were the occurrence of grade 3/4 hematologic toxicity and peripheral blood parameters reaching a nadir. Linear regression models were generated for the nadirs and receiver operating characteristic (ROC) curves for the occurrence of grade 3/4 hematologic toxicity. RESULTS: Thirty-five patients were enrolled. Women presented higher dose-volume parameters of BMact, BMtot, and lymphocyte nadir (ALCnadir%) than men. Models for the prediction of ALCnadir% (V5-V20BMtot, V5-V30BMact) and platelet nadir (PLTnadir%; V5-V10BMtot, V5-V20BMact) were statistically significant. In the ROC curves, a baseline lymphocyte level of 1.81â¯× 103/ml was adopted as the cutoff for predicting grade 3/4 lymphopenia, with specificity of 77.8% and sensitivity of 73.1%. The multivariate linear regression model for ALCnadir% had R2â¯= 0.53, pâ¯= 0.038. In the tenth step of selection, V5BMact (pâ¯= 0.002) and gender (pâ¯= 0.019) remained. The multivariate linear regression model for PLTnadir% had R2â¯= 0.20, pâ¯= 0.34. In the sixth step of selection, V15BMact remained (pâ¯= 0.026). CONCLUSION: The dose-volume parameters of BMact serve as better predictors of ALCnadir% and PLTnadir% than BMtot.
Asunto(s)
Adenocarcinoma/terapia , Médula Ósea/efectos de los fármacos , Médula Ósea/efectos de la radiación , Quimioradioterapia/efectos adversos , Enfermedades Hematológicas/etiología , Imagen por Resonancia Magnética/métodos , Terapia Neoadyuvante/efectos adversos , Radioterapia Conformacional/efectos adversos , Neoplasias del Recto/terapia , Adenocarcinoma/sangre , Adenocarcinoma/cirugía , Anciano , Antimetabolitos Antineoplásicos/uso terapéutico , Médula Ósea/diagnóstico por imagen , Terapia Combinada , Relación Dosis-Respuesta en la Radiación , Femenino , Fluorouracilo/uso terapéutico , Enfermedades Hematológicas/inducido químicamente , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Curva ROC , Planificación de la Radioterapia Asistida por Computador , Neoplasias del Recto/sangre , Neoplasias del Recto/cirugía , Sensibilidad y Especificidad , Tomografía Computarizada por Rayos XRESUMEN
Angiocentric features are uncommon in high-grade World Health Organisation (WHO) brain tumours, whilst they are typical for WHO grade I tumours, e.g. angiocentric gliomas. We present an unusual glial tumour that occurred in a 59-year-old man. The tumour had equivocal radiologic and histopathologic features, especially a characteristic angiocentric pattern, low-to-moderate Ki67, and dot-like epithelial membrane antigen expression. The tumour did not show features characteristic for glioblastoma; however, it recurred as glioblastoma four months later. Based on this case, we show that high-grade WHO brain tumours may show an angiocentric pattern typical for low-grade WHO brain tumours, such as angiocentric gliomas.
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PURPOSE: Brachytherapy (BT), due to rapid dose fall off and minor set-up errors, should be superior to external beam radiotherapy (EBRT) for treatment of lesions in difficult locations like nose and earlobe. Evidences in this field are scarce. We describe computed tomography (CT) based surface mould BT for non-melanoma skin cancers (NMSC), and compare its conformity, dose coverage, and tissue sparing ability to EBRT. MATERIAL AND METHODS: We describe procedure of preparation of surface mould applicator and dosimetry parameters of BT plans, which were implemented in 10 individuals with NMSC of nose and earlobe. We evaluated dose coverage by minimal dose to 90% of planning target volume (PTV) (D90), volumes of PTV receiving 90-150% of prescribed dose (PD) (VPTV90-150), conformal index for 90 and 100% of PD (COIN90, COIN100), dose homogeneity index (DHI), dose nonuniformity ratio (DNR), exposure of organs. Prospectively, we created CT-based photons and electrons plans. We compared conformity (COIN90, COIN100), dose coverage of PTV (D90, VPTV90, VPTV100), volumes of body receiving 10-90% of PD (V10-V90) of EBRT and BT plans. RESULTS: We obtained mean BT-DHI = 0.76, BT-DNR = 0.23, EBRT-DHI = 1.26. We observed no significant differences in VPTV90 and D90 between BT and EBRT. Mean BT-VPTV100 (89.4%) was higher than EBRT-VPTV100 (71.2%). Both COIN90 (BT-COIN90 = 0.46 vs. EBRT-COIN90 = 0.21) and COIN100 (BT-COIN100 = 0.52 vs. EBRT-COIN100 = 0.26) were superior for BT plans. We observed more exposure of normal tissues for small doses in BT plans (V10, V20), for high doses in EBRT plans (V70, V90). CONCLUSIONS: Computed tmography-based surface mould brachytherapy for superficial lesions on irregular surfaces is a highly conformal method with good homogeneity. Brachytherapy is superior to EBRT in those locations in terms of conformity and normal tissue sparing ability in high doses.