RESUMO
In preclinical studies, accurate monitoring of tumor dynamics is crucial for understanding cancer biology and evaluating therapeutic interventions. Traditional methods like caliper measurements and bioluminescence imaging (BLI) have limitations, prompting the need for improved imaging techniques. This study introduces a fast-scan high-frequency ultrasound (HFUS) protocol for the longitudinal assessment of syngeneic breast tumor grafts in mice, comparing its performance with caliper, BLI measurements and with histological analysis. The E0771 mammary gland tumor cell line, engineered to express luciferase, was orthotopically grafted into immunocompetent C57BL/6 mice. Tumor growth was monitored longitudinally at multiple timepoints using caliper measurement, HFUS, and BLI, with the latter two modalities assessed against histopathological standards post-euthanasia. The HFUS protocol was designed for rapid, anesthesia-free scanning, focusing on volume estimation, echogenicity, and necrosis visualization. All mice developed tumors, only 20.6% were palpable at day 4. HFUS detected tumors as small as 2.2 mm in average diameter from day 4 post-implantation, with an average scanning duration of 47 s per mouse. It provided a more accurate volume assessment than caliper, with a lower average bias relative to reference tumor volume. HFUS also revealed tumor necrosis, correlating strongly with BLI in terms of tumor volume and cellularity. Notable discrepancies between HFUS and BLI growth rates were attributed to immune cell infiltration. The fast HFUS protocol enables precise and efficient tumor assessment in preclinical studies, offering significant advantages over traditional methods in terms of speed, accuracy, and animal welfare, aligning with the 3R principle in animal research.
Assuntos
Neoplasias Mamárias Animais , Animais , Camundongos , Camundongos Endogâmicos C57BL , Análise Custo-Benefício , Ultrassonografia , Linhagem Celular Tumoral , NecroseRESUMO
BACKGROUND: Early hormone-positive breast cancers typically have favorable outcomes, yet long-term surveillance is crucial due to the risk of late recurrences. While many studies associate MMP-11 expression with poor prognosis in breast cancer, few focus on early-stage cases. This study explores MMP-11 as an early prognostic marker in hormone-positive breast cancers. METHODS: In this retrospective study, 228 women with early hormone-positive invasive ductal carcinoma, treated surgically between 2011 and 2016, were included. MMP-11 expression was measured by immunohistochemistry, and its association with clinical and MRI data was analyzed. RESULTS: Among the patients (aged 31-89, median 60, with average tumor size of 15.7 mm), MMP-11 staining was observed in half of the cases. This positivity correlated with higher uPA levels and tumor grade but not with nodal status or size. Furthermore, MMP-11 positivity showed specific associations with MRI features. Over a follow-up period of 6.5 years, only 12 oncological events occurred. Disease-free survival was linked to Ki67 and MMP-11. CONCLUSION: MMP-11, primarily present in tumor-surrounding stromal cells, correlates with tumor grade and uPA levels. MMP-11 immunohistochemical score demonstrates a suggestive trend in association with disease-free survival, independent of Ki67 and other traditional prognostic factors. This highlights the potential of MMP-11 as a valuable marker in managing early hormone-positive breast cancer.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Intervalo Livre de Doença , Neoplasias da Mama/diagnóstico por imagem , Antígeno Ki-67 , Metaloproteinase 11 da Matriz , Estudos Retrospectivos , Imageamento por Ressonância Magnética , HormôniosRESUMO
BACKGROUND: MiT family translocation renal cell carcinoma (TRCC) is a rare and aggressive subgroup of renal cell carcinoma harboring high expression of c-MET. While TRCC response rates to VEGF receptor tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors are limited, efficacy of cabozantinib (a VEGFR, MET, and AXL inhibitor) in this subgroup is unclear. METHODS: We performed a multicenter, retrospective, international cohort study of patients with TRCC treated with cabozantinib. The main objectives were to estimate response rate according to RECIST 1.1 and to analyze progression-free survival (PFS) and overall survival (OS). RESULTS: Fifty-two patients with metastatic TRCC treated in the participating centers and evaluable for response were included. Median age at metastatic diagnosis was 40 years (IQR 28.5-53). Patients' IMDC risk groups at diagnosis were favorable (9/52), intermediate (35/52), and poor (8/52). Eleven (21.2%) patients received cabozantinib as frontline therapy, 15 (28.8%) at second line, and 26 (50%) at third line and beyond. The proportion of patients who achieved an objective response was 17.3%, including 2 complete responses and 7 partial responses. For 26 (50%) patients, stable disease was the best response. With a median follow-up of 25.1 months (IQR 12.6-39), median PFS was 6.8 months (95%CI 4.6-16.3) and median OS was 18.3 months (95%CI 17.0-30.6). No difference of response was identified according to fusion transcript features. CONCLUSION: This real-world study provides evidence of the activity of cabozantinib in TRCC, with more durable responses than those observed historically with other VEGFR-TKIs or ICIs.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Adulto , Humanos , Pessoa de Meia-Idade , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Estudos de Coortes , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Estudos RetrospectivosRESUMO
BACKGROUND: To prove feasibility of multimodal and temporal fusion of laparoscopic images with preoperative computed tomography scans for a real-time in vivo-targeted lymph node (TLN) detection during minimally invasive pelvic lymphadenectomy and to validate and enable such guidance for safe and accurate sentinel lymph node dissection, including anatomical landmarks in an experimental model. METHODS: A measurement campaign determined the most accurate tracking system (UR5-Cobot versus NDI Polaris). The subsequent interventions on two pigs consisted of an identification of artificial TLN and anatomical landmarks without and with augmented reality (AR) assistance. The AR overlay on target structures was quantitatively evaluated. The clinical relevance of our system was assessed via a questionnaire completed by experienced and trainee surgeons. RESULTS: An AR-based robotic assistance system that performed real-time multimodal and temporal fusion of laparoscopic images with preoperative medical images was developed and tested. It enabled the detection of TLN and their surrounding anatomical structures during pelvic lymphadenectomy. Accuracy of the CT overlay was > 90%, with overflow rates < 6%. When comparing AR to direct vision, we found that scores were significatively higher in AR for all target structures. AR aided both experienced surgeons and trainees, whether it was for TLN, ureter, or vessel identification. CONCLUSION: This computer-assisted system was reliable, safe, and accurate, and the present achievements represent a first step toward a clinical study.
Assuntos
Realidade Aumentada , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Linfonodo Sentinela , Cirurgia Assistida por Computador , Humanos , Feminino , Suínos , Animais , Procedimentos Cirúrgicos Robóticos/métodos , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Laparoscopia/métodos , Procedimentos Cirúrgicos em Ginecologia , Cirurgia Assistida por Computador/métodosRESUMO
STUDY OBJECTIVE: To describe the anatomy of the nerves during a laparoscopic retroperitoneal para-aortic lymphadenectomy with prioritization of their preservation. DESIGN: Demonstration of a nerve-preserving para-aortic lymphadenectomy. SETTING: A 65-year-old woman with no significant medical history underwent diagnostic laparoscopy for evaluation of a right ovarian mass. In the absence of peritoneal carcinomatosis, bilateral adnexectomy wasperformed with pathology revealing a high-grade tubo-ovarian serous carcinoma. In accordance with French Guidelines for management of ovarian cancer, operative staging including pelvic and para-aortic lymphadenectomy was recommended [1]. Final pathology following staging surgery was consistent with stage IA high-grade serous ovarian cancer prompting administration of adjuvant chemotherapy postoperatively. INTERVENTIONS: We performed a lumbo-aortic lymphadenectomy with preservation of the following nerves: the superior hypogastric plexus, the lumbar splanchnic nerves and the sympathetic trunk. CONCLUSION: Although there are conflicting data as to the benefit of staging lymphadenectomy in women with presumed early stage high-grade serous ovarian cancer, current French Guidelines recommend its performance. When doing so, effort should be made to avoid injury to adjacent normal structures, and in doing so, minimize potential morbidity. The neural structures preserved in this case are part of the sympathetic contingent and participate in the innervation of the abdomen and pelvic viscera. The sympathetic contingent is responsible for the vasomotricity but is also involved in the contraction of the internal genitalia during orgasm and in the inhibition of the peristaltic contractions of the rectum. As such, its preservation may avoid certain postoperative complaints. When possible to do so without compromising essential elements of a cancer surgery, preservation of nerves should be considered.
Assuntos
Laparoscopia , Neoplasias Ovarianas , Doenças da Bexiga Urinária , Idoso , Carcinoma Epitelial do Ovário/cirurgia , Feminino , Humanos , Plexo Hipogástrico/patologia , Excisão de Linfonodo , Masculino , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Doenças da Bexiga Urinária/cirurgiaRESUMO
INTRODUCTION: Testing for COVID-19 is a cornerstone of pandemic control. If conducted inappropriately, nasopharyngeal swab collection can be painful and preanalytical sample collection errors may lead to false negative results. Our objective was to develop a realistic and easily available synthetic simulator for nasopharyngeal swab collection. MATERIALS AND METHODS: The nasopharyngeal swab collection simulator was designed through different development steps: segmentation, computer-aided design (CAD), and 3D printing. The model was 3D printed using PolyJet technology, which allows multi-material printing using hard and soft materials. RESULTS: The simulator splits in the parasagittal plane close to the septum to allow better visualization and understanding of nasal cavity landmarks. The model is able to simulate the softness and texture of different structural elements. The simulator allows the user to conduct realistic nasopharyngeal swab collection. A colored pad on the posterior wall of the nasopharynx provides real-time feedback to the user. The simulator also permits incorrect swab insertion, which is of obvious benefit from a training perspective. Comprehensive 3D files for printing and full instructions for manufacturing the simulator is freely available online via an open access link. CONCLUSION: In the context of the COVID-19 pandemic, we developed a nasopharyngeal swab collection simulator which can be produced by 3D printing via an open access link, which offers complete operating instructions.
Assuntos
COVID-19 , Teste para COVID-19 , Humanos , Nasofaringe , Pandemias , Impressão Tridimensional , SARS-CoV-2RESUMO
Background uPA and PAI-1 are breast cancer biomarkers that evaluate the benefit of chemotherapy (CT) for HER2-negative, estrogen receptor-positive, low or intermediate grade patients. Our objectives were to observe clinical routine use of uPA/PAI-1 and to build a new therapeutic decision tree integrating uPA/PAI-1. Methods We observed the concordance between CT indications proposed by a canonical decision tree representative of French practices (not including uPA/PAI-1) and actual CT prescriptions decided by a medical board which included uPA/PAI-1. We used a method of machine learning for the analysis of concordant and non-concordant CT prescriptions to generate a novel scheme for CT indications. Results We observed a concordance rate of 71% between indications proposed by the canonical decision tree and actual prescriptions. Discrepancies were due to CT contraindications, high tumor grade and uPA/PAI-1 level. Altogether, uPA/PAI-1 were a decisive factor for the final decision in 17% of cases by avoiding CT prescription in two-thirds of cases and inducing CT in other cases. Remarkably, we noted that in routine practice, elevated uPA/PAI-1 levels seem not to be considered as a sufficient indication for CT for N≤3, Ki 67≤30% tumors, but are considered in association with at least one additional marker such as Ki 67>14%, vascular invasion and ER-H score <150. Conclusions This study highlights that in the routine clinical practice uPA/PAI-1 are never used as the sole indication for CT. Combined with other routinely used biomarkers, uPA/PAI-1 present an added value to orientate the therapeutic choice.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Aprendizado de Máquina , Inibidor 1 de Ativador de Plasminogênio/análise , Ativador de Plasminogênio Tipo Uroquinase/análise , Adulto , Idoso , Biomarcadores Tumorais/análise , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Árvores de Decisões , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Taxa de SobrevidaRESUMO
BACKGROUND: Breast fibromatosis is a rare disease characterized by monoclonal fibroblast proliferation. It has no ability to metastasize but has a high local recurrence rate and often infiltrates surrounding tissues. Surgical treatment is the reference, but recently, new targeted therapies have emerged. We report an original case of a patient with breast fibromatosis who received exclusive medical treatment. Our aim was to analyze these treatments based on the clinical and radiological outcome, iatrogenic effects, and pharmacological action. CASE PRESENTATION: We report the case of a 19-year-old woman who developed a desmoid-type fibromatosis of the lower inner quadrant of the right breast, measuring 50 × 25 mm (i.e., a volume of 27.4 cm3). Initial surgery was not possible because of potential esthetic and functional prejudice. Thus, she had an exclusive medical treatment including several lines: NSAIDs with tamoxifen and triptorelin, followed by sorafenib, then interferon α2b, and finally sunitinib. With tyrosine-kinase inhibitors (TKIs) (sunitinib), a significant partial response was observed (57% reduction of the maximal tumoral volume). For each treatment, we provided the clinical and radiological outcome in association with known pharmacological action. CONCLUSIONS: TKI had been an interesting alternative option to initial surgery, providing at least a partial response and potentially allowing less mutilating surgery. However, no pharmacological mechanism can unequivocally explain TKI efficacy. In general, breast fibromatosis should be treated along with oncologist and interventional radiologists in a trans-disciplinary modality, thus offering an adapted treatment for this particular desmoid-type fibromatosis localization.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Fibromatose Agressiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Neoplasias da Mama/patologia , Feminino , Fibromatose Agressiva/patologia , Humanos , Prognóstico , Proteínas Tirosina Quinases/antagonistas & inibidores , Adulto JovemRESUMO
BACKGROUND: The aim of this study was the evaluation of breast MRI in determining the size and focality of invasive non-metastatic breast cancers. METHODS: The prospective, single-centre study conducted in 2015 compared preoperative MRI with histological analysis of mastectomy. RESULTS: One hundred one mastectomies from 98 patients were extensively analysed. The rates of false-positive and false-negative MRI were 2 and 4% respectively. The sensitivity of breast MRI was 84.7% for the detection of all invasive foci, 69% for single foci and 65.7% for multiple foci. In the evaluation of tumour size, the Spearman rank correlation coefficient r between the sizes obtained by MRI and histology was 0.62. The MRI-based prediction of a complete response to neoadjuvant chemotherapy was 75%. DISCUSSION: MRI exhibits high sensitivity in the detection of invasive breast cancers. False positives were linked to the inflammatory nature of the tumour bed. False negatives were associated with small or low-grade tumours and their retro-areolar location. The size of T1 tumours was overestimated by an average of 7%, but MRI was the most efficient procedure. The sensitivity of MRI for the diagnosis of unifocal tumours was higher than that for multifocal sites. Our study confirmed the positive contribution of preoperative MRI for invasive lobular carcinomas and complete response predictions after neoadjuvant chemotherapy.
Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Imageamento por Ressonância Magnética/métodos , Mastectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/cirurgia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Estudos ProspectivosRESUMO
BACKGROUND: Autogenous arteriovenous fistula (AVF) is the best vascular access (VA) for hemodialysis, but its creation is still a critical procedure. Physical examination, vascular mapping and doppler ultrasound (DUS) evaluation are recommended for AVF planning, but they can not provide direct indication on AVF outcome. We recently developed and validated in a clinical trial a patient-specific computational model to predict pre-operatively the blood flow volume (BFV) in AVF for different surgical configuration on the basis of demographic, clinical and DUS data. In the present investigation we tested power of prediction and usability of the computational model in routine clinical setting. METHODS: We developed a web-based system (AVF.SIM) that integrates the computational model in a single procedure, including data collection and transfer, simulation management and data storage. A usability test on observational data was designed to compare predicted vs. measured BFV and evaluate the acceptance of the system in the clinical setting. Six Italian nephrology units were involved in the evaluation for a 6-month period that included all incident dialysis patients with indication for AVF surgery. RESULTS: Out of the 74 patients, complete data from 60 patients were included in the final dataset. Predicted brachial BFV at 40 days after surgery showed a good correlation with measured values (in average 787 ± 306 vs. 751 ± 267 mL/min, R = 0.81, p < 0.001). For distal AVFs the mean difference (±SD) between predicted vs. measured BFV was -2.0 ± 20.9%, with 50% of predicted values in the range of 86-121% of measured BFV. Feedbacks provided by clinicians indicate that AVF.SIM is easy to use and well accepted in clinical routine, with limited additional workload. CONCLUSIONS: Clinical use of computational modeling for AVF surgical planning can help the surgeon to select the best surgical strategy, reducing AVF early failures and complications. This approach allows individualization of VA care, with the aim to reduce the costs associated with VA dysfunction, and to improve AVF clinical outcome.
Assuntos
Derivação Arteriovenosa Cirúrgica/métodos , Complicações Pós-Operatórias/prevenção & controle , Diálise Renal/métodos , Adulto , Idoso , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Derivação Arteriovenosa Cirúrgica/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos TeóricosRESUMO
BACKGROUND: International guidelines issued recommendations for vascular access (VA) care for hemodialysis, but there are no registry data regarding this topic in Italy. METHODS: A survey consisting of 17 items was sent to all Italian dialysis wards, via the Italian Society of Nephrology (SIN) website, from April to June 2021. The items were defined, discussed and approved by experts in vascular access management within the Italian Society of Nephrology. A total of 124 dialysis units answered, accounting for 14% of all dialysis units. The survey thus encompasses all regions within the country, with some regional variations in terms of adherence. RESULTS: One hundred twenty-four facilities provided data, regarding 12,276 patients: 61% had an arteriovenous fistula (AVF), 34% had a central venous catheter (CVC), and 5% had an arteriovenous graft (AVG). Among them, two-thirds of the facilities reported having a vascular access care pathway, formally standardized in 79% of cases. Forty-six % of centers had a fully equipped vascular access care pathway, encompassing preoperative mapping (80%), vascular access setup (71%), arteriovenous fistula maturation monitoring (76%), first-level (80%) and second-level (78%) monitoring, and surgical and/or endovascular treatment of complications (66%). Vascular access monitoring was computerized in 39% of facilities. First-level monitoring (physical examination) was primarily done by nurses in two-thirds of facilities. Of note, 45% of centers had nurses who were skilled in ultrasound-guided cannulation. Quite surprisingly, facilities with less than 100 patients had a greater prevalence of arteriovenous fistulas than those with more than 100 patients (p = 0.0023). A protocolled vascular access care pathway was associated with a higher likelihood of having an arteriovenous fistula (70% AVF vs 42,1% CVC; p = 0.04). The presence in the facility of interventional nephrologists or nurses with ultrasound-guided cannulation skills significantly reduced the prevalence of central venous catheters. CONCLUSION: These survey data further strengthen the need for formal and shared vascular access monitoring protocols.
RESUMO
OBJECTIVE: To establish a predictive model for adverse immediate neonatal adaptation (INA) in fetuses with suspected severe fetal growth restriction (FGR) after 34 gestational weeks (GW). METHODS: We conducted a retrospective observational study at the University Hospitals of Strasbourg between 2000 and 2020, including 1,220 women with a singleton pregnancy and suspicion of severe FGR who delivered from 34 GW. The primary outcome (composite) was INA defined as Apgar 5-minute score <7, arterial pH <7.10, immediate transfer to pediatrics, or the need for resuscitation at birth. We developed and tested a logistic regression predictive model. RESULTS: Adverse INA occurred in 316 deliveries. The model included six features available before labor: parity, gestational age, diabetes, middle cerebral artery Doppler, cerebral-placental inversion, onset of labor. The model could predict individual risk of adverse INA with confidence interval at 95 %. Taking an optimal cutoff threshold of 32 %, performances were: sensitivity 66 %; specificity 83 %; positive and negative predictive values 60 % and 87 % respectively, and area under the curve 78 %. DISCUSSION: The predictive model showed good performances and a proof of concept that INA could be predicted with pre-labor characteristics, and needs to be investigated further.
Assuntos
Retardo do Crescimento Fetal , Recém-Nascido Pequeno para a Idade Gestacional , Criança , Feminino , Humanos , Recém-Nascido , Gravidez , Feto/irrigação sanguínea , Idade Gestacional , Placenta/irrigação sanguínea , Terceiro Trimestre da Gravidez , Ultrassonografia Pré-NatalRESUMO
BACKGROUND: Since in Italy there are no official data on vascular access (VA) for hemodialysis the Vascular Access Project Group (VAPG) of the Italian Society of Nephrology (SIN) designed a national survey. METHODS: A 35-question survey was designed and sent it to the Italian facilities through the SIN website. The basic questions were the prevalence, the location, and the surveillance of VA, the bedside use of ultrasound, the use of fluoroscopy for central venous catheter (CVC) placement, and of buttonhole technique, the role of nephrologist in the access creation. RESULT: The questionnaire was completed in June 2022 by 161 facilities. The survey registered 15,499 patients, approximately one-third of the Italian dialysis population. The prevalence of arteriovenous fistula (AVF), arteriovenous Graft (AVG), and CVC were 61.8%, 3.7%, and 34.5% respectively. The AVF location was 50% in distal forearm, 20% in meanproximal forearm, 30% in upper arm. For AVF creation, nephrologists were involved in 72% of facilities while for CVC placement in 62%. As regards VA monitoring, 21% of the facilities did not have a surveillance protocol; 60% did not register AVF thrombosis and 53% did not register CVC infections. Most of facilities use the fluoroscope during CVC placement, 37% when needed, and 22% never. Ultrasound-guided puncture of complex AVFs was used by 80% of facilities. Buttonhole puncture was used in 5% of patients. CONCLUSIONS: Some considerations emerge from the survey data: (1) The increasing CVC prevalence compared to DOPPS 5 study. (2) The low rate of AVG prevalence. (3) The nephrologist is the operator in many VA procedures. (4) The fluoroscopy for CVC placement and the US-guide puncture of the complex AVF are widely used in most facilities. (5) The practice of the buttonhole is not widespread. (6) When the operator is the nephrologist more distal fistulas are performed.
RESUMO
INTRODUCTION: Cervical cancer is a global public health concern. Despite ESGO recommendations and FIGO classification changes, management of locally advanced cervical cancer (LACC) remains debated in France. Our study aimed to review LACC treatment practices and assess adherence to ESGO recommendations among different practitioners. METHODS: From February 2021 to August 2022, we conducted a survey among gynecologic oncology surgeons, radiation oncologists, and medical oncologists practicing in France and managing LACC (FIGO stages IB3-IVA) according to the 2018 FIGO classification. We analyzed responses against the 2018 ESGO recommendations as a "gold standard." RESULTS: Among 115 respondents (56% radiation oncologists, 30% surgeons, 13% medical oncologists), 48.6% of gynecologic surgeons didn't perform para-aortic lymphadenectomy (PAL) with significant radiologic pelvic involvement. PAL, when indicated by PET-CT, was more common in university hospitals (66.7% of surgeons). Surgeons in university hospitals also followed ESGO recommendations more closely. Overall, compliance with all ESGO recommendations was low: 5.7% of surgeons, 21.5% of radiation oncologists, and 60% of medical oncologists. Prophylactic para-aortic irradiation, per ESGO, was more frequent in comprehensive cancer centers (52% of radiation oncologists). CONCLUSION: Adherence to ESGO recommendations for LACC treatment appears low in France, particularly in surgery, with limited PAL in cases of lymph node negativity on PET-CT. However, these recommendations are more often followed by surgeons in university hospitals and radiation oncologists in cancer centers. Adherence to these recommendations may impact patient survival and warrants evaluation of care quality, justifying the organization of LACC management in expert centers.
Assuntos
Fidelidade a Diretrizes , Excisão de Linfonodo , Padrões de Prática Médica , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/patologia , França , Fidelidade a Diretrizes/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Estadiamento de Neoplasias , Guias de Prática Clínica como Assunto , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Oncologistas , Radio-Oncologistas , Equipe de Assistência ao Paciente , Cirurgiões , Inquéritos e QuestionáriosAssuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Mamilos/patologia , Neoplasias da Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Mamilos/diagnóstico por imagemRESUMO
CONTEXT: Adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) is debated as benefits are inconstant. Molecular signatures for DCIS have been developed to stratify the risk of local recurrence (LR) and therefore guide the decision of RT. OBJECTIVE: To evaluate, in women with DCIS treated by BCS, the impact of adjuvant RT on LR according to the molecular signature risk stratification. METHODOLOGY: We conducted a systematic review and meta-analysis of five articles including women with DCIS treated by BCS and with a molecular assay performed to stratify the risk, comparing the effect of BCS and RT versus BCS alone on LR including ipsilateral invasive (InvBE) and total breast events (TotBE). RESULTS: The meta-analysis included 3478 women and evaluated two molecular signatures: Oncotype Dx DCIS (prognostic of LR), and DCISionRT (prognostic of LR and predictive of RT benefit). For DCISionRT, in the high-risk group, the pooled hazard ratio of BCS + RT versus BCS was 0.39 (95%CI 0.20-0.77) for InvBE and 0.34 (95%CI 0.22-0.52) for TotBE. In the low-risk group, the pooled hazard ratio of BCS + RT versus BCS was significant for TotBE at 0.62 (95%CI 0.39-0.99); however, it was not significant for InvBE (HR = 0.58 (95%CI 0.25-1.32)), Discussion: Molecular signatures are able to discriminate high- and low-risk women, high-risk ones having a significant benefit of RT in the reduction of invasive and in situ local recurrences, while in low-risk ones RT did not have a benefit for preventing invasive breast recurrence. The risk prediction of molecular signatures is independent of other risk stratification tools developed in DCIS, and have a tendency toward RT de-escalation. Further studies are needed to assess the impact on mortality.
RESUMO
BACKGROUND: class III obese women, are at a higher risk of cesarean section during labor, and cesarean section is responsible for increased maternal and neonatal morbidity in this population. OBJECTIVE: the objective of this project was to develop a method with which to quantify cesarean section risk before labor. METHODS: this is a multicentric retrospective cohort study conducted on 410 nulliparous class III obese pregnant women who attempted vaginal delivery in two French university hospitals. We developed two predictive algorithms (a logistic regression and a random forest models) and assessed performance levels and compared them. RESULTS: the logistic regression model found that only initial weight and labor induction were significant in the prediction of unplanned cesarean section. The probability forest was able to predict cesarean section probability using only two pre-labor characteristics: initial weight and labor induction. Its performances were higher and were calculated for a cut-point of 49.5% risk and the results were (with 95% confidence intervals): area under the curve 0.70 (0.62,0.78), accuracy 0.66 (0.58, 0.73), specificity 0.87 (0.77, 0.93), and sensitivity 0.44 (0.32, 0.55). CONCLUSIONS: this is an innovative and effective approach to predicting unplanned CS risk in this population and could play a role in the choice of a trial of labor versus planned cesarean section. Further studies are needed, especially a prospective clinical trial. FUNDING: French state funds "Plan Investissements d'Avenir" and Agence Nationale de la Recherche.
Assuntos
Cesárea , Obesidade , Recém-Nascido , Feminino , Gravidez , Humanos , Estudos Retrospectivos , Estudos Prospectivos , Obesidade/epidemiologia , Aprendizado de MáquinaRESUMO
Pathological complete response (pCR) after neoadjuvant systemic treatment (NST) is an important prognostic factor in HER2-positive breast cancer. The majority of HER2-positive breast cancers are amplified at the HER2 gene locus, several genes are co-amplified with HER2, and a subset of them are co-expressed. The STARD3 gene belongs to the HER2 amplicon, and its role as a predictive marker was never addressed. The objective of this study was to investigate the predictive value of STARD3 protein expression on NST pathological response in HER2-positive breast cancer. In addition, we studied the prognostic value of this marker. METHODS: We conducted a retrospective study between 2007 and 2020 on 112 patients with non-metastatic HER2-positive breast cancer treated by NST and then by surgery. We developed an immunohistochemistry assay for STARD3 expression and subcellular localization and determined a score for STARD3-positivity. As STARD3 is an endosomal protein, its expression was considered positive if the intracellular signal pattern was granular. RESULTS: In this series, pCR was achieved in half of the patients. STARD3 was positive in 86.6% of cases and was significantly associated with pCR in univariate analysis (p = 0.013) and after adjustment on other known pathological parameters (p = 0.044). Performances on pCR prediction showed high sensitivity (96%) and negative predictive value (87%), while specificity was 23% and positive predictive value was 56%. Overall, specific, relapse-free, and distant metastasis-free survivals were similar among STARD3 positive and negative groups, independently of other prognosis factors. CONCLUSION: NST is an opportunity for HER2-positive cancers. In this series of over a hundred HER2-positive and non-metastatic patients, a STARD3-negative score was associated with the absence of pathological complete response. This study suggests that determining STARD3 overexpression status on initial biopsies of HER2-positive tumors is an added value for the management of a subset of patients with high probability of no pathological response.
RESUMO
PURPOSE: A considerable amount of valuable information is present in electronic health records (EHRs) however it remains inaccessible because it is embedded into unstructured narrative documents that cannot be easily analyzed. We wanted to develop and evaluate a methodology able to extract and structure information from electronic health records in breast cancer. METHODS: We developed a software platform called Onconum (ClinicalTrials.gov Identifier: NCT02810093) which uses a hybrid method relying on machine learning approaches and rule-based lexical methods. It is based on natural language processing techniques that allows a targeted analysis of free-text medical data related to breast cancer, independently of any pre-existing dictionary, in a French context (available in N files). We then evaluated it on a validation cohort called Senometry. FINDINGS: Senometry cohort included 9,599 patients with breast cancer (both invasive and in situ), treated between 2000 and 2017 in the breast cancer unit of Strasbourg University Hospitals. Extraction rates ranged from 45 to 100%, depending on the type of each parameter. Precision of extracted information was 68%-94% compared to a structured cohort, and 89%-98% compared to manually structured databases and it retrieved more rare occurrences compared to another database search engine (+17%). INTERPRETATION: This innovative method can accurately structure relevant medical information embedded in EHRs in the context of breast cancer. Missing data handling is the main limitation of this method however multiple sources can be incorporated to reduce this limit. Nevertheless, this methodology does not need neither pre-existing dictionaries nor manually annotated corpora. It can therefore be easily implemented in non-English-speaking countries and in other diseases outside breast cancer, and it allows prospective inclusion of new patients.