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BACKGROUND: This study aimed to investigate the serum metabolite profiles during neoadjuvant chemoradiotherapy (NCRT) in locally advanced rectal cancer (LARC) using liquid chromatography-mass spectrometry (LC-MS) metabolomics analysis. METHODS: 60 serum samples were collected from 20 patients with LARC before, during, and after radiotherapy. LC-MS metabolomics analysis was performed to identify the metabolite variations. Functional annotation was applied to discover altered metabolic pathways. The key metabolites were screened and their ability to predict sensitivity to radiotherapy was calculated using random forests and ROC curves. RESULTS: The results showed that NCRT led to significant changes in the serum metabolite profiles. The serum metabolic profiles showed an apparent separation between different time points and different sensitivity groups. Moreover, the functional annotation showed that the differential metabolites were associated with a series of important metabolic pathways. Pre-radiotherapy (3Z,6Z)-3,6-Nonadiena and pro-radiotherapy 1-Hydroxyibuprofen showed good predictive performance in discriminating the sensitive and non-sensitive group to NCRT, with an AUC of 0.812 and 0.75, respectively. Importantly, the combination of different metabolites significantly increased the predictive ability. CONCLUSION: This study demonstrated the potential of LC-MS metabolomics for revealing the serum metabolite profiles during NCRT in LARC. The identified metabolites may serve as potential biomarkers and therapeutic targets for the management of this disease. Furthermore, the understanding of the affected metabolic pathways may help design more personalized therapeutic strategies for LARC patients.
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Cervical cancer (CC) remains among the most frequent cancers worldwide despite advances in screening and the development of vaccines against human papillomavirus (HPV), involved in virtually all cases of CC. In mid-income countries, a substantial proportion of the cases are diagnosed in advanced stages, and around 40% of them are diagnosed in women under 49 years, just below the global median age. This suggests that members of this age group share common risk factors, such as chronic inflammation. In this work, we studied samples from 46 patients below 45 years old, searching for a miRNA profile regulating cancer pathways. We found 615 differentially expressed miRNAs between tumor samples and healthy tissues. Through bioinformatic analysis, we found that several of them targeted elements of the JAK/STAT pathway and other inflammation-related pathways. We validated the interactions of miR-30a and miR-34c with JAK1 and STAT3, respectively, through dual-luciferase and expression assays in cervical carcinoma-derived cell lines. Finally, through knockdown experiments, we observed that these miRNAs decreased viability and promoted proliferation in HeLa cells. This work contributes to understanding the mechanisms through which HPV regulates inflammation, in addition to its canonical oncogenic function, and brings attention to the JAK/STAT signaling pathway as a possible diagnostic marker for CC patients younger than 45 years. To our knowledge to date, there has been no previous description of a panel of miRNAs or even ncRNAs in young women with locally advanced cervical cancer.
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Regulação Neoplásica da Expressão Gênica , Inflamação , MicroRNAs , Fator de Transcrição STAT3 , Transdução de Sinais , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de Sinais/genética , Adulto , Inflamação/genética , Inflamação/patologia , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Células HeLa , Janus Quinase 1/metabolismo , Janus Quinase 1/genética , Proliferação de Células/genética , Linhagem Celular Tumoral , Pessoa de Meia-IdadeRESUMO
Background: Surgical resection is not always achievable in thyroid cancer patients. Neoadjuvant therapy is rarely used, but recent trends favor multikinase inhibitors or selective tyrosine kinase inhibitors. These aim to reduce tumor volume, enabling previously unfeasible surgeries. Patients and Methods: Consecutive patients with locally advanced malignant thyroid tumors who received systemic therapies with a neoadjuvant intention were included in this retrospective multicenter case series conducted in five Latin American referral centers. Primary outcomes were pre- versus postneoadjuvant response evaluations using the Response Evaluation Criteria in Solid Tumors, feasibility of surgery, and completeness of resection. Secondary outcomes were mortality and status at the last visit. Results: Twenty-seven patients were included in this analysis. Patients with unresectable differentiated thyroid cancer (DTC) or poorly differentiated thyroid cancer (PDTC) received sorafenib (n = 6) or lenvatinib (n = 12), those with medullary thyroid cancer (MTC) were treated with vandetanib (n = 5) or selpercatinib (n = 1), and those with anaplastic thyroid cancer (ATC) harboring a BRAFV600E mutation (n = 3) received dabrafenib and trametinib. The median patient age was 66 years (range 12-82), and 52% of the patients were female. In patients with PTC and PDTC, the median reduction in the diameter of the primary tumor was 25% (range 0-100%) after a median of 6 months of treatment. Surgical intervention was performed in 10 (55%) of the patients. Among these, six patients (60%) achieved R0/R1 resection status. Six patients with MTC had a median reduction in tumor diameter of 24.5% (range 1-49) after a median treatment time of 9.5 months. Only one patient receiving selpercatinib, with a tumoral reduction of 25% could undergo surgery, resulting in an R2 resection due to extensive mediastinal extension. Three patients with ATC showed a median tumor diameter reduction of 42% (range 6.7-50) after a median treatment time of 2 months. Two patients underwent surgical intervention and achieved R1 and R2 resection, respectively. Conclusions: While neoadjuvant therapy achieved tumoral responses, surgical resection was feasible in 55% of DTC, 33% of ATC, and 16% of MTC patients, with R0/R1 resection in 26% of the cohort, underscoring the need for patient selection and further research in this area.
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Terapia Neoadjuvante , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/terapia , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/cirurgia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Adulto , Idoso de 80 Anos ou mais , Adulto Jovem , Adolescente , Criança , Tireoidectomia , América Latina , Resultado do Tratamento , Inibidores de Proteínas Quinases/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/terapia , QuinolinasRESUMO
INTRODUCTION: Recent advances in the treatment of locally advanced NSCLC have led to changes in the standard of care for this disease. For the selection of the best approach strategy for each patient, it is necessary the homogenization of diagnostic and therapeutic interventions, as well as the promotion of the evaluation of patients by a multidisciplinary oncology team. OBJECTIVE: Development of an expert consensus document with suggestions for the approach and treatment of locally advanced NSCLC leaded by Spanish Lung Cancer Group GECP. METHODS: Between March and July 2023, a panel of 28 experts was formed. Using a mixed technique (Delphi/nominal group) under the guidance of a coordinating group, consensus was reached in 4 phases: 1. Literature review and definition of discussion topics 2. First round of voting 3. Communicating the results and second round of voting 4. Definition of conclusions in nominal group meeting. Responses were consolidated using medians and interquartile ranges. The threshold for agreement was defined as 85% of the votes. RESULTS: New and controversial situations regarding the diagnosis and management of locally advanced NSCLC were analyzed and reconciled based on evidence and clinical experience. Discussion issues included: molecular diagnosis and biomarkers, radiologic and surgical diagnosis, mediastinal staging, role of the multidisciplinary thoracic committee, neoadjuvant treatment indications, evaluation of response to neoadjuvant treatment, postoperative evaluation, and follow-up. CONCLUSIONS: Consensus clinical suggestions were generated on the most relevant scenarios such as diagnosis, staging and treatment of locally advanced lung cancer, which will serve to support decision-making in daily practice.
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Carcinoma Pulmonar de Células não Pequenas , Consenso , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/terapia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Espanha , Equipe de Assistência ao Paciente , Técnica Delphi , Estadiamento de NeoplasiasRESUMO
Objective: This study aimed to identify the information needs and factors for making informed treatment decisions among a diverse group of locally advanced cervical cancer (LACC) patients. Methods: Semi-structured interviews were conducted with LACC patients of diverse demographic and socioeconomic backgrounds within two years of their cancer diagnosis. Trained moderators asked open-ended questions about patients' cancer journeys. Transcripts were analyzed using NVivo software to identify emergent themes. Results: In 2022, 92 LACC patients in the United States (n = 26), Brazil (n = 25), China (n = 25), and Germany (n = 16) participated in the study. Physicians were valued sources of information, providing patients with details on prognosis, treatment options, and side effects. While most patients trusted their physicians, one-third sought a second opinion to validate their diagnosis or find a more trusted physician.Most patients conducted their own research on treatment options, side effects, causes of LACC, symptoms, and others' experiences. Challenges to information searches included understanding medical terms, finding relevant information, and evaluating source credibility.Overall, patients felt knowledgeable enough to participate in treatment decisions, either by accepting the recommended treatment or collaborating with their physicians. Nearly one-third of patients desired a more significant role in the decision-making process. Conclusion: This study highlights the importance of physicians providing LACC patients comprehensive and understandable information, while involving them in the decision-making process. Understanding LACC patients' motivations to seek information and their willingness to actively engage in treatment decisions can lead to improved patient satisfaction in their cancer care.
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BACKGROUND AND OBJECTIVES: Neoadjuvant chemotherapy (NCH) has demonstrated efficacy in downsizing tumors and facilitating less extensive surgery. However, immediate breast reconstruction (IBR) after NCH has raised concerns regarding higher complication rates. This study evaluates the impact of NCH on outcomes following IBR with a latissimus dorsi flap and implant (LDI) after mastectomy. METHODS: Cases from a prospective maintained database were reviewed, and patients classified according to whether or not they received NCH. Risk factors and major and minor complications in both groups were then analyzed. RESULTS: Among the 196 patients who underwent 198 IBR procedures, 38.4% received NCH and 66.1% did not. The overall complication rate was 46.7% in the non-NCH group and 53.3% in the NCH group (p = 0.650). The presence of comorbidities increased the likelihood of any complication (odds ratio [OR]: 3.46; 95% confidence interval [CI]: 1.38-8.66; p = 0.008) as well as major complications (OR: 3.35; 95% CI: 1.03-10.95; p = 0.045). Although patients in the NCH group experienced more major complications (10.5% vs. 4.9%; p = 0.134) and early loss of breast reconstruction (3.9% vs. 0.8%; p = 0.128), these findings were not statistically significant. CONCLUSION: This study found no statistically significant association between NCH and higher risk of complications or loss of IBR with LDI after mastectomy.
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Neoplasias da Mama , Mamoplastia , Músculos Superficiais do Dorso , Humanos , Feminino , Mastectomia/efeitos adversos , Mastectomia/métodos , Terapia Neoadjuvante/métodos , Resultado do Tratamento , Estudos Prospectivos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Neoplasias da Mama/etiologia , Mamoplastia/efeitos adversos , Mamoplastia/métodos , Silicones , Estudos RetrospectivosRESUMO
PURPOSE: This study aimed to assess the impact of ypT stage and tumor regression grade (TRG) on the long-term prognosis of patients with locally advanced rectal cancer (LARC) stage ypT1-4N0 after neoadjuvant chemoradiotherapy (NCRT). METHODS: We retrospectively analyzed 585 patients with histologically diagnosed middle-low LARC (cT3-4 or cN + by pelvic MRI) from 2014 to 2019. All patients underwent NCRT, followed by total mesorectal excision. Disease-free survival (DFS) rates were compared among patients with different ypT stages and TRGs by Kaplan-Meier survival analysis. The chi-square test was used to analyze the relationship between clinicopathological or therapeutic factors and ypT stage. RESULTS: The median follow-up was 35.8 months (range 2.8-71.8 months). The 3-year DFS was 79.5%. A better 3-year DFS was achieved in patients with a pathologic complete response (94.0% vs. 74.3%, p < 0.001) and those in the ypT0-2 (86.5% vs. 66.6%, p < 0.001), ypN0 (85.0% vs. 60.2%, p < 0.001), and TRG0 + 1 (83.1% vs. 73.0%, p = 0.004) subgroups. A total of 309 patients (52.8%) achieved stage ypT1-4N0 after surgery. Among these patients, the ypT1-2N0 subgroup achieved a significantly higher 3-year DFS than the ypT3-4N0 subgroup (85.4% vs. 72.8%, p = 0.018); in contrast, the 3-year DFS did not significantly differ between the TRG1 and TRG2 + 3 subgroups (79.9% vs. 81.1%, p = 0.833). In the ypT1-2N0 or ypT3-4N0 subgroup, different TRG had no significant effect on failure patterns. CONCLUSIONS: For LARC patients with a ypT1-4N0 status after NCRT, ypT stage may be a more effective predictor of long-term prognosis than TRG.
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Terapia Neoadjuvante , Neoplasias Retais , Humanos , Resultado do Tratamento , Estudos Retrospectivos , Estadiamento de Neoplasias , Quimiorradioterapia , Prognóstico , Neoplasias Retais/patologiaRESUMO
Chemoresistance to standard neoadjuvant treatment commonly occurs in locally advanced breast cancer, particularly in the luminal subtype, which is hormone receptor-positive and represents the most common subtype of breast cancer associated with the worst outcomes. Identifying the genes associated with chemoresistance is crucial for understanding the underlying mechanisms and discovering effective treatments. In this study, we aimed to identify genes linked to neoadjuvant chemotherapy resistance in 62 retrospectively included patients with luminal breast cancer. Whole RNA sequencing of 12 patient biopsies revealed 269 differentially expressed genes in chemoresistant patients. We further validated eight highly correlated genes associated with resistance. Among these, solute carrier family 12 member 1 (SLC12A1) and glutamate ionotropic AMPA type subunit 4 (GRIA4), both implicated in ion transport, showed the strongest association with chemoresistance. Notably, SLC12A1 expression was downregulated, while protein levels of glutamate receptor 4 (GLUR4), encoded by GRIA4, were elevated in patients with a worse prognosis. Our results suggest a potential link between SLC12A1 gene expression and GLUR4 protein levels with chemoresistance in luminal breast cancer. In particular, GLUR4 protein could serve as a potential target for drug intervention to overcome chemoresistance.
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Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas de Membrana Transportadoras , Terapia Neoadjuvante , Estudos Retrospectivos , Membro 1 da Família 12 de Carreador de SolutoRESUMO
Background: Recent data suggest that breast-conserving surgery (BCS) may positively impact overall survival (OS) in early breast cancer. However, the role of BCS in locally advanced breast cancer (LABC) following neoadjuvant therapy (NAT) remains uncertain. Methods: We conducted a retrospective cohort study involving 530 LABC patients who underwent surgery after NAT between 2010 and 2015. Outcomes examined included OS, distant recurrence rates (DRR), and loco-regional recurrence rates (LRRs). Results: Among the 927 breast cancer patients who received NAT, 530 were eligible for our study. Of these, 24.6% underwent BCS, while 75.4% underwent mastectomy (MS). The median follow-up duration was 79 months. BCS patients exhibited a higher pathological complete response (PCR) rate compared to those who underwent MS (22.3% vs. 10%, p < 0.001). The 6-year OS rates for BCS and MS were 81.5% and 62%, respectively (p < 0.000). In multivariate OS analysis, MS was associated with worse outcomes (OR 1.678; 95% CI 1.069-2.635; p = 0.024), as was body mass index (BMI) (OR 1.031; 95% CI 1.006-1.058; p = 0.017), and stage IIIB or IIIC (OR 2.450; 95% CI 1.561-3.846; p < 0.000). Conversely, PCR (OR 0.42; 95% CI 0.220-0.801; p = 0.008) was associated with improved survival. DRR was significantly lower in BCS (15.4%) compared to MS (36.8%) (OR 0.298; 95% CI 0.177-0.504). LRRs were comparable between BCS (9.2%) and MS (9.5%) (OR 0.693; 95% CI 0.347-1.383). Conclusion: Our findings suggest that BCS is oncologically safe, even for patients with large lesions, and is associated with superior OS rates compared to MS. Additionally, lower BMI, lower pretreatment stage, and achieving PCR were associated with improved survival outcomes.
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Thoracoabdominal (TA) flaps are a good option for primary closure of small and medium defects after mastectomy for locally advanced breast tumours. Although they have a higher rate of necrosis than myocutaneous flaps, they can be easily performed by breast surgeons. Few studies on this procedure have been reported, and we have been unable to identify any prior publications reporting breast reconstruction with TA flaps.
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Neoplasias da Mama , Mamoplastia , Retalho Miocutâneo , Humanos , Feminino , Mastectomia , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Mamoplastia/métodos , Retalho Miocutâneo/patologia , Retalho Miocutâneo/cirurgia , Necrose/cirurgiaRESUMO
OPINION STATEMENT: Nasopharyngeal carcinoma (NPC) is a rare malignancy, endemic in China, that is commonly diagnosed in locally advanced scenarios. Its pathogenesis is strongly associated with Epstein-Barr virus (EBV), an infection for which measuring EBV plasma DNA levels has helped as a prognostic factor guiding treatment options, including a stronger treatment in those with high titers. Additionally, tobacco and alcohol are often implicated in EBV-negative patients. The local disease is treated with radiotherapy alone, preferentially intensity modulated radiotherapy. For locally advanced disease, the backbone treatment is concurrent chemoradiotherapy with the ongoing research dilemma being adding adjuvant chemotherapy or induction chemotherapy. The ongoing research is focused not only on identifying patients that will benefit from adjuvant or induction chemotherapy, but also on identifying the best chemotherapeutic regimen, regimen alternatives to diminish toxicity, the role that immune checkpoint inhibitors play, and the use of molecularly guided treatment targeting patients with NPC whether driven by EBV or tobacco and alcohol. Knowing the precise oncogenesis of NPC not only offers a better understanding of the role that EBV plays in this tumor but also helps create targeted therapies that could potentially block important pathways such as the NF-κB pathway. Much is yet to be done, but the prognosis and management of NPC patients have changed drastically, offering precise treatment methods and excellent control of the disease, even in locally advanced scenarios.
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Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/etiologia , Carcinoma Nasofaríngeo/terapia , Infecções por Vírus Epstein-Barr/terapia , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/etiologia , Neoplasias Nasofaríngeas/terapia , Herpesvirus Humano 4/genética , Prognóstico , QuimiorradioterapiaRESUMO
PURPOSE: To analyze the effect of cisplatin cycles on the clinical outcomes of patients with locally advanced cervical cancer (LACC) treated with concurrent chemoradiotherapy (CCRT). METHODS: This study included 749 patients with LACC treated with CCRT between January 2011 and December 2015. A receiver operating characteristic (ROC) curve was used to analyze the optimal cut-off of cisplatin cycles in predicting clinical outcomes. Clinicopathological features of the patients were compared using the Chi-square test. Prognosis was assessed using log-rank tests and Cox proportional hazard models. Toxicities were compared among different cisplatin cycle groups. RESULTS: Based on the ROC curve, the optimal cut-off of the cisplatin cycles was 4.5 (sensitivity, 64.3%; specificity, 54.3%). The 3-year overall, disease-free, loco-regional relapse-free, and distant metastasis-free survival for patients with low-cycles (cisplatin cycles < 5) and high-cycles (≥ 5) were 81.5% and 89.0% (P < 0.001), 73.4% and 80.1% (P = 0.024), 83.0% and 90.8% (P = 0.005), and 84.9% and 86.8% (P = 0.271), respectively. In multivariate analysis, cisplatin cycles were an independent prognostic factor for overall survival. In the subgroup analysis of high-cycle patients, patients who received over five cisplatin cycles had similar overall, disease-free, loco-regional relapse-free, and distant metastasis-free survival to patients treated with five cycles. Acute and late toxicities were not different between the two groups. CONCLUSION: Cisplatin cycles were associated with overall, disease-free, and loco-regional relapse-free survival in LACC patients who received CCRT. Five cycles appeared to be the optimal number of cisplatin cycles during CCRT.
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Neoplasias Nasofaríngeas , Neoplasias do Colo do Útero , Feminino , Humanos , Cisplatino , Carcinoma Nasofaríngeo/tratamento farmacológico , Resultado do Tratamento , Neoplasias do Colo do Útero/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Quimiorradioterapia , Neoplasias Nasofaríngeas/terapia , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
Pancreatic ductal adenocarcinoma remains a global health challenge and is predicted to soon become the second leading cause of cancer death in developed countries. Currently, surgical resection in combination with systemic chemotherapy offers the only chance of cure or long-term survival. However, only 20% of cases are diagnosed with anatomically resectable disease. Neoadjuvant treatment followed by highly complex surgical procedures has been studied over the last decade with promising short- and long-term results in patients with locally advanced pancreatic ductal adenocarcinoma (LAPC). In recent years, a wide variety of complex surgical techniques that involve extended pancreatectomies, including portomesenteric venous resection, arterial resection, or multi-organ resection, have emerged to optimize local control of the disease and improve postoperative outcomes. Although there are multiple surgical techniques described in the literature to improve outcomes in LAPC, the comprehensive view of these strategies remains underdeveloped. We aim to describe the preoperative surgical planning as well different surgical resections strategies in LAPC after neoadjuvant treatment in an integrated way for selected patients with no other potentially curative option other than surgery.
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Background: Breast cancer is the most frequent malignant tumor in women. Objective: To identify clinico-pathological and molecular markers as predictors of survival in patients with locally advanced breast cancer (LABC). Methods: Retrospective and observational study. The clinical factors of clinico-pathological and molecular predictors in relation with overall survival (OS) were assessed by the survival function, baseline hazard with smoothing and Cox regression. Results: 126 patients were assessed. OS at five years was significantly superior in patients with clinical stage IIIA (87%; p < 0.001), grade 2 tumor (81%; p < 0.001), pathological node stage (ypN0: 90%; p < .001), low-risk Nottingham prognostic index (86%; p < 0.001) and luminal A subtype (88%; p = 0.022). Baseline hazard with smoothing exhibited an increase in the mortality rate at 50 months for the luminal B/ HER2+ subtype compared with other subtypes. The multivariate analysis ascertained that the stage ypN2-3 (hazard ratio [HR] = 7.3; 95% confidence interval [95% CI]: 2.2 to 23.9) and the HER2+ nonluminal (HR = 7.8; 95% CI: 2 to 29.6) and triple negative (HR = 5.4; 95% CI: 1.7 to 17.2) subtypes were associated with a poor OS. Conclusions: The comprehensive evaluation of the molecular marker and clinico-pathological factors provides more accurate predictive and prognostic information. The nodal stage and molecular subtype are suitable clinical parameters on survival for LABC patients.
Introducción: el cáncer de mama es el tumor maligno más frecuente en las mujeres. Objetivo: identificar marcadores clínico-patológicos y moleculares como predictores de la supervivencia en pacientes con cáncer de mama localmente avanzado (CMLA). Material y métodos: estudio retrospectivo y observacional. Los factores clínico-patológicos y moleculares fueron evaluados en relación con la supervivencia global (SG) mediante la función de supervivencia, riesgo basal con suavizamiento y regresión de Cox. Resultados: 126 pacientes fueron evaluadas. La SG a cinco años fue significativamente superior en pacientes con estadio clínico IIIA (87%; p < 0.001), tumor de grado 2 (81%; p < 0.001), ausencia de ganglios patológicos (ypN0: 90%; p < 0.001) y en el subtipo luminal A (88%; p = 0.022). El riesgo basal con suavizamiento exhibió un incremento en la tasa de mortalidad a los 50 meses para el subtipo luminal B/ HER2+ comparado con los otros subtipos. En el análisis multivariado, el estadio ypN2-3 (razón de riesgo [RR] = 7.3; intervalo de confianza del 95% [IC 95%]: 2.2 a 23.9) y los subtipos HER2+ (RR = 7.8; IC 95%: 2 a 29.6) y triple negativo (RR= 5.4; IC 95%: 1.7 a 17.2) se asociaron con una pobre SG. Conclusiones: la evaluación integral del marcador molecular y de los factores clínico-patológicos proporciona información predictiva y pronóstica más precisa. El estadio ganglionar y subtipo molecular son parámetros adecuados con un impacto pronóstico en la SG para las pacientes con CMLA.
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Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Prognóstico , Estudos Retrospectivos , Receptor ErbB-2 , Modelos de Riscos Proporcionais , Biomarcadores TumoraisRESUMO
El manejo multimodal del cáncer de recto, localmente avanzado (LARC), se ha convertido en las últimas décadas en el estándar terapéutico de este tipo de tumores, logrando cifras de recidiva local global alrededor del 10%. Sin embargo, las tasas de sobrevida global (OS) y de sobrevida libre de enfermedad (DFS) no superan el 75% en la mayoría de las series, debido a las fallas a distancia. La investigación de nuevas terapias que logren un control efectivo de la enfermedad sistémica se ha focalizado en agregar a la radioterapia pélvica distintos esquemas de quimioterapia en la etapa preoperatoria, es decir, neoadyuvante. En esta revisión se discuten los distintos esquemas denominados genéricamente TNT (total neoadjuvant therapy), las ventajas y las limitaciones de este nuevo enfrentamiento del LARC, basado principalmente en los estudios prospectivos y aleatorizados disponibles a la fecha, con foco en los resultados en OS y DFS.
Neoadjuvant chemoradiation followed by surgery with or without adjuvant chemotherapy has remained the mainstay of treatment of locally advanced rectal cancer (LARC) for the past two decades. Although this regimen has reduced rates of local recurrence to 10% or less, rates of systemic failure are 20 to 30%, leading to a 5-year survival of 70-75%, at best. This situation has led to investigations into the use of total neoadjuvant therapy in the form of induction or consolidation chemotherapy. This review put the focus on final outcomes like overall survival and disease-free survival based on the available prospective and randomized studies about different schemes of TNT.
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BACKGROUND: Whole-tumor apparent diffusion coefficient (ADC) histogram analysis is relevant to predicting the neoadjuvant chemoradiation therapy (nCRT) response in patients with locally advanced rectal cancer (LARC). AIM: To evaluate the performance of ADC histogram-derived parameters for predicting the outcomes of patients with LARC. METHODS: This is a single-center, retrospective study, which included 48 patients with LARC. All patients underwent a pre-treatment magnetic resonance imaging (MRI) scan for primary tumor staging and a second restaging MRI for response evaluation. The sample was distributed as follows: 18 responder patients (R) and 30 non-responders (non-R). Eight parameters derived from the whole-lesion histogram analysis (ADCmean, skewness, kurtosis, and ADC10th, 25th, 50th, 75th, 90th percentiles), as well as the ADCmean from the hot spot region of interest (ROI), were calculated for each patient before and after treatment. Then all data were compared between R and non-R using the Mann-Whitney U test. Two measures of diagnostic accuracy were applied: the receiver operating characteristic curve and the diagnostic odds ratio (DOR). We also reported intra- and interobserver variability by calculating the intraclass correlation coefficient (ICC). RESULTS: Post-nCRT kurtosis, as well as post-nCRT skewness, were significantly lower in R than in non-R (both P < 0.001, respectively). We also found that, after treatment, R had a larger loss of both kurtosis and skewness than non-R (∆%kurtosis and ∆skewness, P < 0.001). Other parameters that demonstrated changes between groups were post-nCRT ADC10th, ∆%ADC10th, ∆%ADCmean, and ROI ∆%ADCmean. However, the best diagnostic performance was achieved by ∆%kurtosis at a threshold of 11.85% (Area under the receiver operating characteristic curve [AUC] = 0.991, DOR = 376), followed by post-nCRT kurtosis = 0.78 × 10-3 mm2/s (AUC = 0.985, DOR = 375.3), ∆skewness = 0.16 (AUC = 0.885, DOR = 192.2) and post-nCRT skewness = 1.59 × 10-3 mm2/s (AUC = 0.815, DOR = 168.6). Finally, intraclass correlation coefficient analysis showed excellent intraobserver and interobserver agreement, ensuring the implementation of histogram analysis into routine clinical practice. CONCLUSION: Whole-tumor ADC histogram parameters, particularly kurtosis and skewness, are relevant biomarkers for predicting the nCRT response in LARC. Both parameters appear to be more reliable than ADCmean from one-slice ROI.
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Imagem de Difusão por Ressonância Magnética , Neoplasias Retais , Imagem de Difusão por Ressonância Magnética/métodos , Humanos , Imageamento por Ressonância Magnética , Curva ROC , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/terapia , Estudos RetrospectivosRESUMO
The Brazilian Society of Surgical Oncology organized a group of oncological surgeons to discuss surgical aspects associated with locally advanced breast carcinoma. This article reviews the indications, different surgeries (thoracoabdominal or myocutaneous flaps), and associated complications. It discusses special conditions such as invasion of the chest wall and interscapular thoracic disarticulation. It makes recommendations based on the literature regarding clinical findings, tumor conditions, response to neoadjuvant therapy, choice of flaps in surgery, and tumor biology.
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Neoplasias da Mama , Oncologia Cirúrgica , Parede Torácica , Brasil , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Recidiva Local de Neoplasia/cirurgia , Retalhos Cirúrgicos , Parede Torácica/cirurgiaRESUMO
BACKGROUND: Even with different histologic origins, squamous cell carcinoma (SCC) and adenocarcinoma (AC) are considered a single entity, and the first-line treatment is the same. Locally advanced disease at the diagnosis of cervical cancer is the most important prognostic factor, the recurrence rate is high, making it necessary to evaluate prognostic factors other than clinical or radiological staging; histology could be one of them but continues to be controversial. The aim of this study was to evaluate tumor histology as a prognostic factor in terms of treatment outcomes, disease-free survival (DFS) and overall survival (OS) in a retrospective cohort of patients with Locally Advanced Cervical Carcinoma (LACC). METHODS: The records of 1291patients with LACC were reviewed, all of them were treated with 45-50 Gy of external beam radiotherapy with concurrent chemotherapy and brachytherapy. A descriptive and comparative analysis was conducted. Treatment response was analyzed by the chi-square test; DFS and OS were calculated for each histology with the Kaplan-Meier method and compared with the log-rank test; and the Cox model was applied for the multivariate analysis. RESULTS: We included 1291 patients with LACC treated from 2005 to 2014, of which 1154 (89·4%) had SCC and 137 (10·6%) had AC. Complete response to treatment was achieved in 933 (80·8%) patients with SCC and 113 (82·5%) patients with AC. Recurrence of the disease was reported in 29·9% of SCC patients and 31·9% of AC patients. Five-year DFS was 70% for SCC and 62·2% for AC. The five-year OS rates were 74·3% and 60% for SCC and AC, respectively. The mean DFS was 48·8 months for SCC vs 46·10 for AC (p = 0·043), the mean OS was 50·8 for SCC and 47·0 for AC (p = 0·002). CONCLUSION: Our findings support the hypothesis that SCC and AC are different clinical entities. TRIAL REGISTRATION: NCT04537273 .
Assuntos
Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Adenocarcinoma/patologia , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologiaRESUMO
The clinical and pathological responses to multimodal neoadjuvant therapy in locally advanced rectal cancers (LARCs) remain unpredictable, and robust biomarkers are still lacking. Recent studies have shown that tumors present somatic molecular alterations related to better treatment response, and it is also clear that tumor-associated bacteria are modulators of chemotherapy and immunotherapy efficacy, therefore having implications for long-term survivorship and a good potential as the biomarkers of outcome. Here, we performed whole exome sequencing and 16S ribosomal RNA (rRNA) amplicon sequencing from 44 pre-treatment LARC biopsies from Argentinian and Brazilian patients, treated with neoadjuvant chemoradiotherapy or total neoadjuvant treatment, searching for predictive biomarkers of response (responders, n = 17; non-responders, n = 27). In general, the somatic landscape of LARC was not capable to predict a response; however, a significant enrichment in mutational signature SBS5 was observed in non-responders (p = 0.0021), as well as the co-occurrence of APC and FAT4 mutations (p < 0.05). Microbiota studies revealed a similar alpha and beta diversity of bacteria between response groups. Yet, the linear discriminant analysis (LDA) of effect size indicated an enrichment of Hungatella, Flavonifractor, and Methanosphaera (LDA score ≥3) in the pre-treatment biopsies of responders, while non-responders had a higher abundance of Enhydrobacter, Paraprevotella (LDA score ≥3) and Finegoldia (LDA score ≥4). Altogether, the evaluation of these biomarkers in pre-treatment biopsies could eventually predict a neoadjuvant treatment response, while in post-treatment samples, it could help in guiding non-operative treatment strategies.
RESUMO
BACKGROUND: Organ sparing by the transanal endoscopic microsurgery (TEM) procedure is a treatment for patients with locally advanced rectal cancer after chemoradiotherapy (CRT) and complete clinical response (cCR). AIMS: To assess the surgical and long-term oncological outcomes of TEM for the treatment in T2-3 rectal cancer after CRT and cCR. METHODS: This study was a retrospective review of a prospective database of patients with rectal cancer who underwent TEM after CRT and cCR from April 2011 to March 2020. RESULTS: 52 patients underwent TEM during a period of 9 years. This group of patients included 27 females and 25 males. The median age was 62 (32-86) years, lesion size was 2.5 (1-4) cm, and lesion distance from the anal verge 7.3 (4-10) cm. Median operative time was 79.5 (25-120) min and hospital stay was 1 day (14 h-4 days). Morbidity rate was 13.5% and reoperation rate due to major complications was 3.8%. Final histological findings confirmed 34 (65.4%) patients with ypT0, 7 (13.5%), 6 (11.5%), and 5 (9.6%) patients with carcinoma ypT1, ypT2, and ypT3, respectively. After a median follow-up period of 86 (5-107) months, 1 (2.4%) patient had local recurrences and 3 (7.3%) distant metastases. The 5-year disease-free survival was 91.7% and 5-year overall survival 89.5%. CONCLUSION: Our experience has shown significant rates of ypT0 and ypT1 associated with excellent long-term results. Performing TEM to treat T2-3N0 rectal cancer after CRT and cCR appears to be an oncologically safe and effective procedure.